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Transverse Vibrations of an Elastically Mounted Cylinder Exposed to an Oscillating Flow | A FEM STUDY ON THE ADDED INERTIA OF AN OSCILLATING CYLINDER IN VISCOUS FLOW | SNARE Function Is Not Involved in Early Endosome Docking | eng_Latn | 19,300 |
LED spectral model characterized by several Gaussian functions | High precision digital control LED spot light source used to calibrate camera | SNARE Function Is Not Involved in Early Endosome Docking | eng_Latn | 19,301 |
Categorical representation of seaman's knots | Data Mining: Concepts, Models and Techniques | SNARE Function Is Not Involved in Early Endosome Docking | eng_Latn | 19,302 |
Development of a stained cell nuclei counting system | Detecting and Segmenting Nanodiscs in Immuno-Electron Micrographs. | Completely Stale Transmitter Channel State Information is Still Very Useful | eng_Latn | 19,303 |
Embeddings in Spaces of Lipschitz Type, Entropy and Approximation Numbers, and Applications | Entropy Numbers of Diagonal Operators of Logarithmic Type | SNARE Function Is Not Involved in Early Endosome Docking | eng_Latn | 19,304 |
3' splice site recognition in nematode trans-splicing involves enhancer-dependent recruitment of U2 snRNP. | The evolution of spliced leader trans-splicing in nematodes. | SNARE Function Is Not Involved in Early Endosome Docking | eng_Latn | 19,305 |
Scaling law for the Lyapunov spectra in globally coupled tent maps | N ov 2 00 5 1 Low-dimensional chaos in populations of strongly-coupled noisy maps | SNARE Function Is Not Involved in Early Endosome Docking | eng_Latn | 19,306 |
Blow-up profiles and life beyond blow-up in the fully parabolic Keller-Segel system | Linear and Quasi-linear Equations of Parabolic Type | Microtubule capture by CENP-E silences BubR1-dependent mitotic checkpoint signaling | eng_Latn | 19,307 |
Multiple-quantum relaxation dispersion NMR spectroscopy probing millisecond time-scale dynamics in proteins: theory and application. | NMR and computational methods for molecular resolution of allosteric pathways in enzyme complexes | Membranoproliferative glomerulonephritis with disruption of the glomerular basement membrane. | eng_Latn | 19,308 |
Two‐phase flow in structured packings: Modeling and calculation on a macroscopic scale | Computational Fluid Dynamics Simulation of Multiphase Flow in Structured Packings | SNARE Function Is Not Involved in Early Endosome Docking | eng_Latn | 19,309 |
THOMAE TYPE FORMULAE FOR SINGULAR ZN CURVES V.Z. ENOLSKI AND T.GRAVA | Weierstrass points, branch points, and moduli of riemann surfaces | SNARE Function Is Not Involved in Early Endosome Docking | yue_Hant | 19,310 |
Multipeak solutions for the Yamabe equation | Nonuniqueness and high energy solutions for a conformally invariant scalar equation | Microtubule capture by CENP-E silences BubR1-dependent mitotic checkpoint signaling | eng_Latn | 19,311 |
Helix-helix interactions are important for the folding, stability, and function of membrane proteins. Here, two independent and complementary methods are used to investigate the nature and distribution of amino acids that mediate helix-helix interactions in membrane and soluble alpha-bundle proteins. The first method characterizes the packing density of individual amino acids in helical proteins based on the van der Waals surface area occluded by surrounding atoms. We have recently used this method to show that transmembrane helices pack more tightly, on average, than helices in soluble proteins. These studies are extended here to characterize the packing of interfacial and noninterfacial amino acids and the packing of amino acids in the interfaces of helices that have either right- or left-handed crossing angles, and either parallel or antiparallel orientations. We show that the most abundant tightly packed interfacial residues in membrane proteins are Gly, Ala, and Ser, and that helices with left-handed crossing angles are more tightly packed on average than helices with right-handed crossing angles. The second method used to characterize helix-helix interactions involves the use of helix contact plots. We find that helices in membrane proteins exhibit a broader distribution of interhelical contacts than helices in soluble proteins. Both helical membrane and soluble proteins make use of a general motif for helix interactions that relies mainly on four residues (Leu, Ala, Ile, Val) to mediate helix interactions in a fashion characteristic of left-handed helical coiled coils. However, a second motif for mediating helix interactions is revealed by the high occurrence and high average packing values of small and polar residues (Ala, Gly, Ser, Thr) in the helix interfaces of membrane proteins. Finally, we show that there is a strong linear correlation between the occurrence of residues in helix-helix interfaces and their packing values, and discuss these results with respect to membrane protein structure prediction and membrane protein stability. | Integral membrane proteins (MPs) are pharmaceutical targets of exceptional importance. Modern methods of three-dimensional protein structure determination often fail to supply the fast growing field of structure-based drug design with the requested MPs' structures. That is why computational modeling techniques gain a special importance for these objects. Among the principal difficulties limiting application of these methods is the low quality of the MPs' models built in silico. In this series of two papers we present a computational approach to the assessment of the packing “quality” of transmembrane (TM) α-helical domains in proteins. The method is based on the concept of protein environment classes, whereby each amino acid residue is described in terms of its environment polarity and accessibility to the membrane. In the first paper we analyze a nonredundant set of 26 TM α-helical domains and compute the residues' propensities to five predefined classes of membrane-protein environments. Here we evaluate... | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 19,312 |
SUMMARY ::: ::: The presence of synaptonemal complexes in the nuclei of young tetraspore mother cells is described for the first time in the red algae. Synaptonemal complexes were found in Janczewskia gardneri Setchell, Levringiella gardneri Setchell, Gonimophyllum skottsbergii Setchell, and Polycoryne gardneri Setchell. The synaptonemal complexes consist of 2 lateral, dark-staining elements from which small fibrils extend to form a less densely staining central element. With minor variations, the dimensions and structure of these synaptonemal complexes correspond to those found in other organisms. | SummaryPost-meiotic tetraspore mother cells of Corallina officinalis L. have been studied by light and electron microscopy. During the course of post-meiotic cellular reorganisation each nucleus becomes surrounded by a complex of precisely oriented endoplasmic reticulum, termed nuclear endoplasmic reticulum. A distinctive feature of this relationship is an electron dense substance in contact with the nuclear surface and extending as groundplasm between the ER cisternae as far as the outer limits of the complex, where it gives place to the ribosome-containing matrix of the general cytoplasm. There is circumstantial evidence to indicate that the extracisternal electron dense material is a product of nucleo-cytoplasmic interaction, and that it is involved in the assembly of ribosomes.The nuclear endoplasmic reticulum appears to be active in the production of smaller swollen cisternal elements, which form frequently anastomosing reticular tracts in the regions between adjacent nuclei. There is structural evidence of vesicular transport of material from the swollen cisternae to the proximal (“forming”) face of the Golgi apparatus.These events are thought to be of fundamental importance in achieving the cellular reorganisation and transformation which occurs after the second meiotic division. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 19,313 |
Polymerization dynamics of single actin filaments coupled with adenosine triphosphate (ATP) hydrolysis is investigated via both theoretical analysis and Brownian dynamics simulations. Brownian dynamics simulations have been applied recently to study the growth behaviors of long filaments as a function of the free actin monomer concentrations, CT, which is found to be in agreement with the associated experiments. In the present study, both ATP cap length and length diffusivity are studied as a function of the free ATP-actin monomer concentrations, CT. The exact analytical expressions are found to be in perfect consistency with Brownian dynamics simulations. Likewise, we find that the length diffusion coefficient is peaked near the critical concentration, CT, cr. It is, therefore, expected that the dependence of length diffusivity on ATP-actin monomer concentrations is utilized to analyze the surprising experiments on the length fluctuations of individual actin filaments. | Actin is an important cytoskeletal protein that serves as a building block to form filament networks that span across the cell. These networks are orchestrated by a myriad of other cytoskeletal entities including the unbranched filament–forming protein formin and branched network–forming protein complex Arp2/3. Computational models have been able to provide insights into many important structural transitions that are involved in forming these networks, and into the nature of interactions essential for actin filament formation and for regulating the behavior of actin-associated proteins. In this review, we summarize a subset of such models that focus on the atomistic features and those that can integrate atomistic features into a larger picture in a multiscale fashion. | ABSTRACTUNC-45A is an ubiquitously expressed protein highly conserved throughout evolution. Most of what we currently know about UNC-45A pertains to its role as a regulator of the actomyosin system... | eng_Latn | 19,314 |
The proper localization of resident membrane proteins to the trans-Golgi network (TGN) involves mechanisms for both TGN retention and retrieval from post-TGN compartments. In this study we report identification of a new gene, GRD20, involved in protein sorting in the TGN/endosomal system of Saccharomyces cerevisiae. A strain carrying a transposon insertion allele of GRD20 exhibited rapid vacuolar degradation of the resident TGN endoprotease Kex2p and aberrantly secreted ;50% of the soluble vacuolar hydrolase carboxypeptidase Y. The Kex2p mislocalization and carboxypeptidase Y missorting phenotypes were exhibited rapidly after loss of Grd20p function in grd20 temperature-sensitive mutant strains, indicating that Grd20p plays a direct role in these processes. Surprisingly, little if any vacuolar degradation was observed for the TGN membrane proteins A-ALP and Vps10p, underscoring a difference in trafficking patterns for these proteins compared with that of Kex2p. A grd20 null mutant strain exhibited extremely slow growth and a defect in polarization of the actin cytoskeleton, and these two phenotypes were invariably linked in a collection of randomly mutagenized grd20 alleles. GRD20 encodes a hydrophilic protein that partially associates with the TGN. The discovery of GRD20 suggests a link between the cytoskeleton and function of the yeast TGN. | Eukaryotic life depends on the spatial and temporal organization of cellular membrane systems. Recent advances in understanding the machinery of vesicle transport have established general principles that underlie a broad variety of physiological processes, including cell surface growth, the biogenesis of distinct intracellular organelles, endocytosis, and the controlled release of hormones and neurotransmitters. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 19,315 |
The analysis of all cell movements and all cell interactions in a vertebrate during the entire period of embryonic development is a fundamental goal in biology. Using DSLM, we recorded the development of entire zebrafish embryos in vivo and with sub-cellular resolution. By imaging at a speed of 1.5 billion volume elements per minute, image data in the order of several terabytes were acquired for each embryo over the time course of an entire day, i.e. up to a stage, in which the embryo comprises 20,000 cells and major organs are in a functional state. By using automated image processing algorithms the image data of each embryo were converted into a digital representation of the embryo (the "digital embryo"), i.e. a database with comprehensive information about migratory tracks and divisions of the embryo's cells. The digital embryos permit to follow single cells as a function of time such that the "fate" as well as the origin of the cells can be reconstructed. By means of these analyses, developmental blueprints of tissues and organs can be determined in a whole-embryo context. Defects in embryonic development or disease models can now be analyzed and understood on a quantitative level. | A long-standing goal of biology is to map the behavior of all cells during vertebrate embryogenesis. We developed digital scanned laser light sheet fluorescence microscopy and recorded nuclei localization and movement in entire wild-type and mutant zebrafish embryos over the first 24 hours of development. Multiview in vivo imaging at 1.5 billion voxels per minute provides "digital embryos," that is, comprehensive databases of cell positions, divisions, and migratory tracks. Our analysis of global cell division patterns reveals a maternally defined initial morphodynamic symmetry break, which identifies the embryonic body axis. We further derive a model of germ layer formation and show that the mesendoderm forms from one-third of the embryo's cells in a single event. Our digital embryos, with 55 million nucleus entries, are provided as a resource. | Berzelius failed to make use of Faraday's electrochemical laws in his laborious determination of equivalent weights. | eng_Latn | 19,316 |
Because of their remarkable roles in electrical cell signaling, voltage-gated cation channels (VGCCs) have been the subject of intense investigations and debate for more than 50 years. Ultimately, the prospective implications of such studies have an impact on our understanding of the molecular properties of VGCCs involved in consciousness, anesthesia, and diseases, to mention a few. The following review aims to summarize our current knowledge of activation of VGCCs by highlighting major methodological innovations in the field and the breakthroughs they allowed. Focusing mainly on insights gained through computer simulations, while acknowledging important experimental findings, we hope to inspire experimentalists to benefit from these approaches in the generation of hypotheses and design of experiments. Also, we outline major future challenges for the field, such as channel modulation, lesser-known receptors, and molecular origins of channel dysfunctions. | A dynamic transmembrane voltage field has been suggested as an intrinsic element in voltage sensor (VS) domains. Here, the dynamic field contribution to the VS energetics was analyzed via electrostatic calculations applied to a number of atomistic structures made available recently. We find that the field is largely static along with the molecular motions of the domain, and more importantly, it is minimally modified across VS variants. This finding implies that sensor domains transfer approximately the same amount of gating charges when moving the electrically charged S4 helix between fixed microscopic configurations. Remarkably, the result means that the observed operational diversity of the domain, including the extension, rate, and voltage dependence of the S4 motion, as dictated by the free energy landscape theory, must be rationalized in terms of dominant variations of its chemical free energy. | This document defines common requirements for Carrier-Grade NATs ::: (CGNs). It updates RFC 4787. | eng_Latn | 19,317 |
A model for the dynamics of actin filament ends along the leading edge of the lamellipodium is analyzed. It contains accounts of nucleation by branching, of deactivation by capping, and of lateral flow along the leading edge by polymerization. A nonlinearity arises from a Michaelis–Menten type modeling of the branching process. For branching rates large enough compared to capping rates, the existence and stability of nontrivial steady states is investigated. The main result is exponential convergence to nontrivial steady states, proven by investigating the decay of an appropriate Lyapunov functional. | BACKGROUND ::: The actin-related proteins Arp2 and Arp3 are part of a seven-protein complex which is localized in the lamellipodia of a variety of cell types, and in actin-rich spots of unknown function. The Arp2/3 complex enhances actin nucleation and causes branching and crosslinking of actin filaments in vitro; in vivo it is thought to drive the formation of lamellipodia and to be a control center for actin-based motility. The Wiskott-Aldrich syndrome protein, WASP, is an adaptor protein implicated in the transmission of signals from tyrosine kinase receptors and small GTPases to the actin cytoskeleton. Scar1 is a member of a new family of proteins related to WASP, and it may also have a role in regulating the actin cytoskeleton. Scar1 is the human homologue of Dictyostelium Scar1, which is thought to connect G-protein-coupled receptors to the actin cytoskeleton. The mammalian Scar family contains at least four members. We have examined the relationships between WASP, Scar1, and the Arp2/3 complex. ::: ::: ::: RESULTS ::: We have identified WASP and its relative Scar1 as proteins that interact with the Arp2/3 complex. We have used deletion analysis to show that both WASP and Scar1 interact with the p21 subunit of the Arp2/3 complex through their carboxyl termini. Overexpression of carboxy-terminal fragments of Scar1 or WASP in cells caused a disruption in the localization of the Arp2/3 complex and, concomitantly, induced a complete loss of lamellipodia and actin spots. The induction of lamellipodia by platelet-derived growth factor was also suppressed by overexpression of the fragment of Scar1 that binds to the Arp2/3 complex. ::: ::: ::: CONCLUSIONS ::: We have identified a conserved sequence domain in proteins of the WASP family that binds to the Arp2/3 complex. Overexpression of this domain in cells disrupts the localization of the Arp2/3 complex and inhibits lamellipodia formation. Our data suggest that WASP-related proteins may regulate the actin cytoskeleton through the Arp2/3 complex. | We report enhancement of the mechanical stability of graphene through a one-step method to disperse gold nanoparticles on the pristine graphene without any added agent. | eng_Latn | 19,318 |
Ultrasound imaging simulations provide an important tool in imaging research. However, realistic imaging simulations involve long execution times and require enormous computational resources that exceed the capabilities of serial computers. In this paper, we present a parallel three-dimensional ultrasound simulator that runs on computer clusters and uses a k-space method to compute acoustic propagation. The simulator achieved a mean error value of 0.57%, which demonstrates its numerical accuracy. Parallel computing enhanced the simulator efficiency by enabling imaging simulations with short execution times. For instance, the parallel execution time of a simulated ultrasound image using 20 cluster nodes was 18.61 hours compared to a serial execution time of 357.50 hours. | My Personal Review: Texts on acoustics approach the subject from many different angles and at many different levels. Pierce's text is classic, rigorous and complete. It should serve the needs of serious students of acoustics for a variety of purposes musical acoustics and sound are my particular perspective.Some writers cater their approach to electrical engineers or to mechanical engineers, assuming that by tieing everything to those disciplines they will make the effort easier for their readers. This may serve well those who come from those disciplines, but may not serve others well and may not serve all applications of acoustics equally well either. Pierce does not do so. His approach is rigorously mathematical and pure, going to the heart of the matter, rather than one of attempting to cut corners by making analogies to other fields that you may or may not know.The book is not for the faint of heart or the mildly curious, it is deep and demanding. But he organizes it superbly and writes intelligently with a wonderful way of integrating the history and development of the science, and the graphics are exceptionally clear and communicative.Highly recommended for the very serious about this subject. My favorite among the books I have consulted. | ABSTRACTUNC-45A is an ubiquitously expressed protein highly conserved throughout evolution. Most of what we currently know about UNC-45A pertains to its role as a regulator of the actomyosin system... | eng_Latn | 19,319 |
Emerging molecular studies have shown that the transcription factor NF-E2-related factor (Nrf2) plays an essential role in cancer chemoprevention. Here, we report the development of a molecular biosensor for rapid detection of antioxidant-responsive element (ARE)-bound Nrf2 protein. The development will provide a molecular assay for high-throughput screening of chemopreventive compounds. Specifically, a double-stranded DNA probe is designed based on the ARE sequence. One of the DNA strands is labeled with a fluorophore on the 5′ end and the complementary strand is labeled with a quencher on the 3′ end. A single-stranded DNA competitor is also designed. The existence of the Nrf2 stabilizes the fluorescent probes and delays the competitor from separating the fluorophore-quencher complex. Therefore, the concentration of the Nrf2 proteins can be measured quantitatively based on the fluorescence intensity. The molecular binding scheme was demonstrated using purified p50 and the detection of endogenous Nrf2 was... | Microfluidics holds great promise to revolutionize various areas of biological engineering, such as single cell analysis, environmental monitoring, regenerative medicine, and point-of-care diagnostics. Despite the fact that intensive efforts have been devoted into the field in the past decades, microfluidics has not yet been adopted widely. It is increasingly realized that an effective system integration strategy that is low cost and broadly applicable to various biological engineering situations is required to fully realize the potential of microfluidics. In this article, we review several promising system integration approaches for microfluidics and discuss their advantages, limitations, and applications. Future advancements of these microfluidic strategies will lead toward translational lab-on-a-chip systems for a wide spectrum of biological engineering applications. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 19,320 |
We review the effects of heavy scalar fields during inflation in the framework of $\mathcal N = 1$ supergravity. Such heavy scalars can be geometric moduli from string compactifications or stabilizer fields from a different sector of the theory. Even when these fields are heavier than the Hubble scale during inflation, they generically cause backreactions which alter the dynamics of the system. Severe problems may arise when the heavy fields break supersymmetry, which is quite generic for K\"ahler moduli. We illustrate these effects in two examples, chaotic inflation and Starobinsky-like inflation. In chaotic inflation the backreaction of heavy K\"ahler moduli causes a flattening of the quadratic potential. In many setups of Starobinsky-like inflation, however, backreactions spoil the flatness of the plateau. | String theory axions are interesting candidates for fields whose potential might be controllable over super-Planckian field ranges and therefore as possible candidates for inflatons in large field inflation. Axion monodromy scenarios are setups where the axion shift symmetry is broken by some effect such that the axion can traverse a large number of periods potentially leading to super-Planckian excursions. We study such scenarios in type IIA string theory where the axion shift symmetry is broken by background fluxes. In particular we calculate the backreaction of the energy density induced by the axion vacuum expectation value on its own field space metric. We find universal behaviour for all the compactifications studied where up to a certain critical axion value there is only a small backreaction effect. Beyond the critical value the backreaction is strong and implies that the proper field distance as measured by the backreacted metric increases at best logarithmically with the axion vev, thereby placing strong limitations on extending the field distance any further. The critical axion value can be made arbitrarily large by the choice of fluxes. However the backreaction of these fluxes on the axion field space metric ensures a precise cancellation such that the proper field distance up to the critical axion value is flux independent and remains sub-Planckian. We also study an axion alignment scenario for type IIA compactifications on a twisted torus with four fundamental axions mixing to leave an axion with an effective decay constant which is flux dependent. There is a choice of fluxes for which the alignment parameter is unconstrained by tadpoles and can in principle lead to a parametrically enhanced effective decay constant. However we show that these fluxes backreact on the fundamental decay constants so as to precisely cancel any enhancement. | Arginine kinase plays an important role in the cellular energy metabolism of invertebrates. Dimeric arginine kinase (dAK) is unique in some marine invertebrates. The effects of Zn 21 on the unfolding and aggregation of dAK from the sea cucumber Stichopus japonicus were investigated. Our results indicated that Zn 21 caused dAK inactivation accompanied by conformational unfolding, the exposure of hydrophobic surface, and aggregation. Kinetic studies showed the inactivation and unfolding of dAK followed biphasic kinetic courses. Zn 21 can affect unfolding and refolding of dAK by trapping the reversible intermediate. Our study provides important information regarding the effect of Zn 21 on | eng_Latn | 19,321 |
Cyanobacteria have a robust circadian oscillator, known as the Kai system. Reconstituted from the purified protein components KaiC, KaiB, and KaiA, it can tick autonomously in the presence of adenosine 5′-triphosphate (ATP). The KaiC hexamers enter a natural 24-hour reaction cycle of autophosphorylation and assembly with KaiB and KaiA in numerous diverse forms. We describe the preparation of stoichiometrically well-defined assemblies of KaiCB and KaiCBA, as monitored by native mass spectrometry, allowing for a structural characterization by single-particle cryo–electron microscopy and mass spectrometry. Our data reveal details of the interactions between the Kai proteins and provide a structural basis to understand periodic assembly of the protein oscillator. | Many organisms use free running circadian clocks to anticipate the day night cycle. However, others organisms use simple stimulus-response strategies ('hourglass clocks') and it is not clear when such strategies are sufficient or even preferable to free running clocks. Here, we find that free running clocks, such as those found in the cyanobacterium Synechococcus elongatus and humans, can efficiently project out light intensity fluctuations due to weather patterns ('external noise') by exploiting their limit cycle attractor. However, such limit cycles are necessarily vulnerable to 'internal noise'. Hence, at sufficiently high internal noise, point attractor-based 'hourglass' clocks, such as those found in a smaller cyanobacterium with low protein copy number, Prochlorococcus marinus, can outperform free running clocks. By interpolating between these two regimes in a diverse range of oscillators drawn from across biology, we demonstrate biochemical clock architectures that are best suited to different relative strengths of external and internal noise. | Perfect Quantum Cloning Machines (QCM) would allow to use quantum nonlocality for arbitrary fast signaling. However perfect QCM cannot exist. We derive a bound on the fidelity of QCM compatible with the no-signaling constraint. This bound equals the fidelity of the Bu\v{z}ek-Hillery QCM. | eng_Latn | 19,322 |
The problem of protein structure prediction is one of the long-standing goals of Computational Biology. Although we are still not able to provide first principle solutions, several shortcuts have been discovered to compute the protein three-dimensional structure when similar protein sequences are available (by means of comparative modeling and remote homology detection). Nonetheless, these approaches can assign structures only to a fraction of proteins in genomes and ab-initio methods are still needed. One relevant step of ab-initio prediction methods is the reconstruction of the protein structures starting from inter-protein residue contacts. In this paper we review the methods developed so far to accomplish the reconstruction task in order to highlight their differences and similarities. The different ap- proaches are fully described and their reported performances, together with their computa- tional complexity, are also discussed. | Matrices of intraglobular contacts and vectors of coordination numbers derived from the amino acid sequence form the basis for computer procedures for the analysis and prediction of the tertiary structure of proteins. Three main modules perform: 1) prediction of the plot of residue-coordination numbers (number of contacts) on the basis of amino-acid sequence; 2) calculation of the matrix of intraglobular contacts on the basis of coordination-numbers plot and amino-acid sequence; and 3) reconstruction of the three-dimensional structure starting with the contact matrix. This approach provides insight into important regularities governing globule formation, for example, problems of interior/exterior residue distribution and apparent residue-residue affinities. The current state of development is illustrated by calculation of the three-dimensional structure of sea snake neurotoxin. > | ABSTRACTUNC-45A is an ubiquitously expressed protein highly conserved throughout evolution. Most of what we currently know about UNC-45A pertains to its role as a regulator of the actomyosin system... | eng_Latn | 19,323 |
Across diverse biological systems—ranging from neural networks to intracellular signaling and genetic regulatory networks—the information about changes in the environment is frequently encoded in the full temporal dynamics of the network nodes. A pressing data-analysis challenge has thus been to efficiently estimate the amount of information that these dynamics convey from experimental data. Here we develop and evaluate decoding-based estimation methods to lower bound the mutual information about a finite set of inputs, encoded in single-cell high-dimensional time series data. For biological reaction networks governed by the chemical Master equation, we derive model-based information approximations and analytical upper bounds, against which we benchmark our proposed model-free decoding estimators. In contrast to the frequently-used k-nearest-neighbor estimator, decoding-based estimators robustly extract a large fraction of the available information from high-dimensional trajectories with a realistic number of data samples. We apply these estimators to previously published data on Erk and Ca2+ signaling in mammalian cells and to yeast stress-response, and find that substantial amount of information about environmental state can be encoded by non-trivial response statistics even in stationary signals. We argue that these single-cell, decoding-based information estimates, rather than the commonly-used tests for significant differences between selected population response statistics, provide a proper and unbiased measure for the performance of biological signaling networks. | The genetic circuits that regulate cellular functions are subject to stochastic fluctuations, or ‘noise’, in the levels of their components. Noise, far from just a nuisance, has begun to be appreciated for its essential role in key cellular activities. Noise functions in both microbial and eukaryotic cells, in multicellular development, and in evolution. It enables coordination of gene expression across large regulons, as well as probabilistic differentiation strategies that function across cell populations. At the longest timescales, noise may facilitate evolutionary transitions. Here we review examples and emerging principles that connect noise, the architecture of the gene circuits in which it is present, and the biological functions it enables. We further indicate some of the important challenges and opportunities going forward. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 19,324 |
Multiciliated cells (MCCs) promote fluid flow through coordinated ciliary beating, which requires properly organized basal bodies (BBs). Airway MCCs have large numbers of BBs, which are uniformly oriented and, as we show here, align linearly. The mechanism for BB alignment is unexplored. To study this mechanism, we developed a long-term and high-resolution live-imaging system and used it to observe green fluorescent protein-centrin2-labeled BBs in cultured mouse tracheal MCCs. During MCC differentiation, the BB array adopted four stereotypical patterns, from a clustering "floret" pattern to the linear "alignment." This alignment process was correlated with BB orientations, revealed by double immunostaining for BBs and their asymmetrically associated basal feet (BF). The BB alignment was disrupted by disturbing apical microtubules with nocodazole and by a BF-depleting Odf2 mutation. We constructed a theoretical model, which indicated that the apical cytoskeleton, acting like a viscoelastic fluid, provides a self-organizing mechanism in tracheal MCCs to align BBs linearly for mucociliary transport. | Multiciliated epithelial cells, called ependymal cells, line the ventricles in the adult brain. Most ependymal cells are born prenatally and are derived from radial glia. Ependymal cells have a remarkable planar polarization that determines orientation of ciliary beating and propulsion of CSF. Disruption of ependymal ciliary beating, by injury or disease, results in aberrant CSF circulation and hydrocephalus, a common disorder of the CNS. Very little is known about the mechanisms guiding ependymal planar polarity and whether this organization is acquired during ependymal cell development or is already present in radial glia. Here we show that basal bodies in ependymal cells in the lateral ventricle walls of adult mice are polarized in two ways: (1) rotational; angle of individual basal bodies with respect to their long axis and (2) translational; the position of basal bodies on the apical surface of the cell. Conditional ablation of motile cilia disrupted rotational orientation, but translational polarity was largely preserved. In contrast, translational polarity was dramatically affected when radial glial primary cilia were ablated earlier in development. Remarkably, radial glia in the embryo have a translational polarity that predicts the orientation of mature ependymal cells. These results suggest that ependymal planar cell polarity is a multistep process initially organized by primary cilia in radial glia and then refined by motile cilia in ependymal cells. | A clustered base transceiver station (BTS) coordination strategy is proposed for a large cellular MIMO network, which includes full intra-cluster coordination to enhance the sum rate and limited inter-cluster coordination to reduce interference for the cluster edge users. Multi-cell block diagonalization is used to coordinate the transmissions across multiple BTSs in the same cluster. To satisfy per-BTS power constraints, three combined precoder and power allocation algorithms are proposed with different performance and complexity tradeoffs. For inter-cluster coordination, the coordination area is chosen to balance fairness for edge users and the achievable sum rate. It is shown that a small cluster size (about 7 cells) is sufficient to obtain most of the sum rate benefits from clustered coordination while greatly relieving channel feedback requirement. Simulations show that the proposed coordination strategy efficiently reduces interference and provides a considerable sum rate gain for cellular MIMO networks. | eng_Latn | 19,325 |
Single-celled protists use elaborate cytoskeletal structures, including arrays of microtubules at the cell periphery, to maintain polarity and rigidity. The obligate intracellular parasite Toxoplasma gondii has unusually stable cortical microtubules beneath the alveoli, a network of flattened membrane vesicles that subtends the plasmalemma. However, anchoring of microtubules along alveolar membranes is not understood. Here, we show that GAPM1a, an integral membrane protein of the alveoli, plays a role in maintaining microtubule stability. Degradation of GAPM1a causes cortical microtubule disorganisation and subsequent depolymerisation. These changes in the cytoskeleton lead to parasites becoming shorter and rounder, which is accompanied by a decrease in cellular volume. Extended GAPM1a depletion leads to severe defects in division, reminiscent of the effect of disrupting other alveolar proteins. We suggest that GAPM proteins link the cortical microtubules to the alveoli and are required to maintain the shape and rigidity of apicomplexan zoites.Cortical microtubules of Toxoplasma gondii are exceptionally stable, but it isn’t known how they are anchored along membranes. Here, Harding et al. show that GAPM proteins localize to the inner membrane complex and are essential for maintaining the structural stability of parasites. | Microtubules are dynamic cytoskeletal structures important for cell division, polarity, and motility and are therefore major targets for anticancer and antiparasite drugs. In the invasive forms of apicomplexan parasites, which are highly polarized and often motile cells, exceptionally stable subpellicular microtubules determine the shape of the parasite, and serve as tracks for vesicle transport. We used cryoelectron tomography to image cytoplasmic structures in three dimensions within intact, rapidly frozen Plasmodium sporozoites. This approach revealed microtubule walls that are extended at the luminal side by an additional 3 nm compared to microtubules of mammalian cells. Fourier analysis revealed an 8-nm longitudinal periodicity of the luminal constituent, suggesting the presence of a molecule interacting with tubulin dimers. In silico generation and analysis of microtubule models confirmed this unexpected topology. Microtubules from extracted sporozoites and Toxoplasma gondii tachyzoites showed a similar density distribution, suggesting that the putative protein is conserved among Apicomplexa and serves to stabilize microtubules. | Transportation occupies one-third of the amount in the logistics costs, and accordingly transportation systems largely influence the performance of the logistics system. This work presents an adaptive data-driven innovative modular approach for solving the real-world vehicle routing problems (VRPs) in the field of logistics. The work consists of two basic units: (i) an innovative multistep algorithm for successful and entirely feasible solving of the VRPs in logistics and (ii) an adaptive approach for adjusting and setting up parameters and constants of the proposed algorithm. The proposed algorithm combines several data transformation approaches, heuristics, and Tabu search. Moreover, as the performance of the algorithm depends on the set of control parameters and constants, a predictive model that adaptively adjusts these parameters and constants according to historical data is proposed. A comparison of the acquired results has been made using the decision support system with predictive models: generalized linear models (GLMs) and support vector machine (SVM). The algorithm, along with the control parameters, which uses the prediction method, was acquired and was incorporated into a web-based enterprise system, which is in use in several big distribution companies in Bosnia and Herzegovina. The results of the proposed algorithm were compared with a set of benchmark instances and validated over real benchmark instances as well. The successful feasibility of the given routes, in a real environment, is also presented. | eng_Latn | 19,326 |
The heterotrimeric protein complex containing the integrin linked kinase (ILK), parvin, and PINCH proteins, termed the IPP complex, is an essential component of focal adhesions, where it interacts with many proteins to mediate signaling from integrin adhesion receptors. Here we conduct a biochemical and structural analysis of the minimal IPP complex, comprising full-length human ILK, the LIM1 domain of PINCH1, and the CH2 domain of α-parvin. We provide a detailed purification protocol for IPP and show that the purified IPP complex is stable and monodisperse in solution. Using small-angle X-ray scattering (SAXS), we also conduct the first structural characterization of IPP, which reveals an elongated shape with dimensions 120×60×40 A. Flexibility analysis using the ensemble optimization method (EOM) is consistent with an IPP complex structure with limited flexibility, raising the possibility that inter-domain interactions exist. However, our studies suggest that the inter-domain linker in ILK is accessible and we detect no inter-domain contacts by gel filtration analysis. This study provides a structural foundation to understand the conformational restraints that govern the IPP complex. | Structural analysis of flexible macromolecular systems such as intrinsically disordered or multidomain proteins with flexible linkers is a difficult task as high-resolution techniques are barely applicable. A new approach, ensemble optimization method (EOM), is proposed to quantitatively characterize flexible proteins in solution using small-angle X-ray scattering (SAXS). The flexibility is taken into account by allowing for the coexistence of different conformations of the protein contributing to the experimental scattering pattern. These conformers are selected using a genetic algorithm from a pool containing a large number of randomly generated models covering the protein configurational space. Quantitative criteria are developed to analyze the EOM selected models and to determine the optimum number of conformers in the ensemble. Simultaneous fitting of multiple scattering patterns from deletion mutants, if available, provides yet more detailed local information about the structure. The efficiency of EOM is demonstrated in model and practical examples on completely or partially unfolded proteins and on multidomain proteins interconnected by linkers. In the latter case, EOM is able to distinguish between rigid and flexible proteins and to directly assess the interdomain contacts. | TRAF2 and NCK-interacting protein kinase (TNIK) is a key regulatory component of the TCF4 and β-catenin transcriptional complex. In this study, the authors identify a TNIK inhibitor that blocks Wnt signalling and Wnt-driven colorectal tumorigenesis in mice. | eng_Latn | 19,327 |
Attosecond spectroscopy is currently restricted to photon energies around 100 eV. We show that under these conditions, electron-electron scatterings, as the photoelectrons leave the metal give rise to a tail of secondary electrons with lower energies and hence a significant background. We develop an analytical model based on an approximate solution to Boltzmann's transport equation, to account for the amount and energy distribution of these secondary electrons. Our theory is in good agreement with the electron spectrum found in a recent attosecond streaking experiment. To suppress the background and gain higher energy resolution, photon sources of higher energy could be advantageous. | This book is designed for the junior-senior thermodynamics course given in all departments as a standard part of the curriculum. The book is devoted to a discussion of some of the basic physical concepts and methods useful in the description of situations involving systems which consist of very many particulars. It attempts, in particular, to introduce the reader to the disciplines of thermodynamics, statistical mechanics, and kinetic theory from a unified and modern point of view. The presentation emphasizes the essential unity of the subject matter and develops physical insight by stressing the microscopic content of the theory. | ABSTRACTUNC-45A is an ubiquitously expressed protein highly conserved throughout evolution. Most of what we currently know about UNC-45A pertains to its role as a regulator of the actomyosin system... | eng_Latn | 19,328 |
Macromolecular X-ray crystallography is routinely applied to understand biological processes at a molecular level. However, significant time and effort are still required to solve and complete many of these structures because of the need for manual interpretation of complex numerical data using many software packages and the repeated use of interactive three-dimensional graphics. PHENIX has been developed to provide a comprehensive system for macromolecular crystallographic structure solution with an emphasis on the automation of all procedures. This has relied on the development of algorithms that minimize or eliminate subjective input, the development of algorithms that automate procedures that are traditionally performed by hand and, finally, the development of a framework that allows a tight integration between the algorithms. ::: ::: ::: Keywords: ::: ::: PHENIX; ::: Python; ::: algorithms | The type VI secretion system (T6SS) is a bacterial macromolecular machine widely distributed in Gram-negative bacteria, which transports effector proteins into eukaryotic host cells or other bacteria. Membrane complexes and a central tubular structure, which resembles the tail of contractile bacteriophages, compose the T6SS. One of the proteins forming this tube is the hemolysin co-regulated protein (Hcp), which acts as virulence factor, as transporter of effectors and as a chaperone. In this study, we present the structure of Hcp from Acinetobacter baumannii, together with functional and oligomerization studies. The structure of this protein exhibits a tight β barrel formed by two β sheets and flanked at one side by a short α-helix. Six Hcp molecules associate to form a donut-shaped hexamer, as observed in both the crystal structure and solution. These results emphasize the importance of this oligomerization state in this family of proteins, despite the low similarity of sequence among them. The structure presented in this study is the first one for a protein forming part of a functional T6SS from A. baumannii. These results will help us to understand the mechanism and function of this secretion system in this opportunistic nosocomial pathogen. | Macromolecular X-ray crystallography is routinely applied to understand biological processes at a molecular level. However, significant time and effort are still required to solve and complete many of these structures because of the need for manual interpretation of complex numerical data using many software packages and the repeated use of interactive three-dimensional graphics. PHENIX has been developed to provide a comprehensive system for macromolecular crystallographic structure solution with an emphasis on the automation of all procedures. This has relied on the development of algorithms that minimize or eliminate subjective input, the development of algorithms that automate procedures that are traditionally performed by hand and, finally, the development of a framework that allows a tight integration between the algorithms. ::: ::: ::: Keywords: ::: ::: PHENIX; ::: Python; ::: algorithms | eng_Latn | 19,329 |
The translocation step of protein elongation entails a large-scale rearrangement of the tRNA-mRNA-ribosome complex. Recent years have seen major advances in unraveling the mechanism of the process on the molecular level. A number of intermediate states have been defined and, in part, characterized structurally. The article reviews the recent evidence that suggests a dynamic role of the ribosome and its ligands during translocation. The focus is on dynamic aspects of tRNA movement and on the role of elongation factor G and GTP hydrolysis in translocation catalysis. The significance of structural changes of the ribosome induced by elongation factor G as well the role of ribosomal RNA are addressed. A functional model of elongation factor G as a motor protein driven by GTP hydrolysis is discussed. | The distances between the anticodon loops of fluorescent tRNAPhe bound to the E site and to either the A or the P site of poly(U)-programmed Escherichia coli ribosomes were measured by fluorescence energy transfer. Donor and acceptor molecules were wybutine and proflavin, respectively, both located 3' to the anticodon of tRNAPhe. The anticodon loops were found to be separated by 42 +/- 10 A (A to E site) and 34 +/- 8 A (P to E site). The latter distance is much larger than the one measured between the anticodon loops of A and P site bound tRNAs [24 +/- 4 A; Paulsen, H., Robertson, J. M., & Wintermeyer, W. (1983) J. Mol. Biol. 167, 411-426], rendering unlikely simultaneous codon-anticodon interaction in the P and E sites. In kinetic stopped-flow measurements, the energy transfer between the anticodon loops of the tRNA molecules was followed during translocation. The transfer efficiency decreases in three steps with apparent rate constants on the order of 1, 0.1, and 0.01 s-1. The fast step is ascribed to the simultaneous displacement of the deacylated tRNAPhe out of the P site and of the N-AcPhe-tRNAPhe from the A site to the P site. The distance between the anticodon loops does not change appreciably during this reaction. A significant separation of the two tRNAs occurs during the intermediate and the slow steps. The latter most likely represents a rearrangement of the posttranslocation complex containing both tRNA molecules.(ABSTRACT TRUNCATED AT 250 WORDS) | Berzelius failed to make use of Faraday's electrochemical laws in his laborious determination of equivalent weights. | eng_Latn | 19,330 |
The directed migration of cell collectives drives the formation of complex organ systems. A characteristic feature of many migrating collectives is a 'tissue-scale' polarity, whereby 'leader' cells at the edge of the tissue guide trailing 'followers' that become assembled into polarised epithelial tissues en route. Here, we combine quantitative imaging and perturbation approaches to investigate epithelial cell state transitions during collective migration and organogenesis, using the zebrafish lateral line primordium as an in vivo model. A readout of three-dimensional cell polarity, based on centrosomal-nucleus axes, allows the transition from migrating leaders to assembled followers to be quantitatively resolved for the first time in vivo. Using live reporters and a novel fluorescent protein timer approach, we investigate changes in cell-cell adhesion underlying this transition by monitoring cadherin receptor localisation and stability. This reveals that while cadherin 2 is expressed across the entire tissue, functional apical junctions are first assembled in the transition zone and become progressively more stable across the leader-follower axis of the tissue. Perturbation experiments demonstrate that the formation of these apical adherens junctions requires dynamic microtubules. However, once stabilised, adherens junction maintenance is microtubule independent. Combined, these data identify a mechanism for regulating leader-to-follower transitions within migrating collectives, based on the relocation and stabilisation of cadherins, and reveal a key role for dynamic microtubules in this process. | Cardiac trabeculae (which are sponge-like muscular structures) form mostly as a result of cardiomyocyte (CM) delamination in zebrafish. Here, the authors identify Nrg2a in zebrafish as a key regulator of trabeculation, and atrial and non-contractile CMs also respond to Nrg2a despite not forming trabeculae. | not available DOI: http://dx.doi.org/10.3329/pulse.v5i2.20263 Pulse Vol.5 July 2011 p.31-40 | eng_Latn | 19,331 |
To date we have been studying the enzymatic oscillatory reaction caused by gradual entry of substrate via semi-permeable membrane. It has been found that many enzymes cause oscillatory reaction. Here we present an oscillatory reaction of enzyme wrapped by liposome. We used catalase as an enzyme, since its oscillatory reaction has been already investigated in detail in the absence of liposome. Distinct oscillation with shorter period than without liposome was obtained. On the other hand, it was shown that the presence of liposome facilitated the permeation rate of hydrogen peroxide through semi-permeable membrane. This is thought to be factor of shortening the oscillation period compared with that in the absence of liposome. Oscillation was also temperature dependent. Our finding may provide an important insight into the study of enzyme reaction taking part in rhythms in living systems. | BACKGROUND ::: Over many years, it has been assumed that enzymes work either in an isolated way, or organized in small catalytic groups. Several studies performed using "metabolic networks models" are helping to understand the degree of functional complexity that characterizes enzymatic dynamic systems. In a previous work, we used "dissipative metabolic networks" (DMNs) to show that enzymes can present a self-organized global functional structure, in which several sets of enzymes are always in an active state, whereas the rest of molecular catalytic sets exhibit dynamics of on-off changing states. We suggested that this kind of global metabolic dynamics might be a genuine and universal functional configuration of the cellular metabolic structure, common to all living cells. Later, a different group has shown experimentally that this kind of functional structure does, indeed, exist in several microorganisms. ::: ::: ::: METHODOLOGY/PRINCIPAL FINDINGS ::: Here we have analyzed around 2.500.000 different DMNs in order to investigate the underlying mechanism of this dynamic global configuration. The numerical analyses that we have performed show that this global configuration is an emergent property inherent to the cellular metabolic dynamics. Concretely, we have found that the existence of a high number of enzymatic subsystems belonging to the DMNs is the fundamental element for the spontaneous emergence of a functional reactive structure characterized by a metabolic core formed by several sets of enzymes always in an active state. ::: ::: ::: CONCLUSIONS/SIGNIFICANCE ::: This self-organized dynamic structure seems to be an intrinsic characteristic of metabolism, common to all living cellular organisms. To better understand cellular functionality, it will be crucial to structurally characterize these enzymatic self-organized global structures. | Berzelius failed to make use of Faraday's electrochemical laws in his laborious determination of equivalent weights. | eng_Latn | 19,332 |
Biological protein materials (BPMs), intriguing hierarchical structures formed by assembly of chemical building blocks, are crucial for critical functions of life. The structural details of BPMs are fascinating: They represent a combination of universally found motifs such as alpha-helices or beta-sheets with highly adapted protein structures such as cytoskeletal networks or spider silk nanocomposites. BPMs combine properties like strength and robustness, self-healing ability, adaptability, changeability, evolvability and others into multi-functional materials at a level unmatched in synthetic materials. The ability to achieve these properties depends critically on the particular traits of these materials, first and foremost their hierarchical architecture and seamless integration of material and structure, from nano to macro. Here, we provide a brief review of this field and outline new research directions, along with a review of recent research results in the development of structure-property relationships of biological protein materials exemplified in a study of vimentin intermediate filaments. | Titin, a 1-microm-long protein found in striated muscle myofibrils, possesses unique elastic and extensibility properties in its I-band region, which is largely composed of a PEVK region (70% proline, glutamic acid, valine, and lysine residue) and seven-strand beta-sandwich immunoglobulin-like (Ig) domains. The behavior of titin as a multistage entropic spring has been shown in atomic force microscope and optical tweezer experiments to partially depend on the reversible unfolding of individual Ig domains. We performed steered molecular dynamics simulations to stretch single titin Ig domains in solution with pulling speeds of 0.5 and 1.0 A/ps. Resulting force-extension profiles exhibit a single dominant peak for each Ig domain unfolding, consistent with the experimentally observed sequential, as opposed to concerted, unfolding of Ig domains under external stretching forces. This force peak can be attributed to an initial burst of backbone hydrogen bonds, which takes place between antiparallel beta-strands A and B and between parallel beta-strands A' and G. Additional features of the simulations, including the position of the force peak and relative unfolding resistance of different Ig domains, can be related to experimental observations. | Berzelius failed to make use of Faraday's electrochemical laws in his laborious determination of equivalent weights. | eng_Latn | 19,333 |
Allosteric communication in proteins is a fundamental and yet unresolved problem of structural biochemistry. Previous findings, from computational biology (Ota, N.; Agard, D. A. J. Mol. Biol. 2005, 351, 345−354), have proposed that heat diffuses in a protein through cognate protein allosteric pathways. This work studied heat diffusion in the well- known PDZ-2 protein, and confirmed that this protein has two cognate allosteric pathways and that heat flows preferentially through these. Also, a new property was also observed for protein structures: heat diffuses asymmetrically through the structures. The underling structure of this asymmetrical heat flow was a normal length hydrogen bond (∼2.85 A) that acted as a thermal rectifier. In contrast, thermal rectification was compromised in short hydrogen bonds (∼2.60 A), giving rise to symmetrical thermal diffusion. Asymmetrical heat diffusion was due, on a higher scale, to the local, structural organization of residues that, in turn, was also mediated by hydrogen bonds. This asymmetrical/symmetrical energy flow may be relevant for allosteric signal communication directionality in proteins and for the control of heat flow in materials science. | Understanding the nature of allostery in DNA-nuclear receptor (NR) complexes is of fundamental importance for drug development since NRs regulate the transcription of a myriad of genes in humans and other metazoans. Here, we investigate allostery in the peroxisome proliferator-activated/retinoid X receptor heterodimer. This important NR complex is a target for antidiabetic drugs since it binds to DNA and functions as a transcription factor essential for insulin sensitization and lipid metabolism. We find evidence of interdependent motions of Ω-loops and PPARγ-DNA binding domain with contacts susceptible to conformational changes and mutations, critical for regulating transcriptional functions in response to sequence-dependent DNA dynamics. Statistical network analysis of the correlated motions, observed in molecular dynamics simulations, shows preferential allosteric pathways with convergence centers comprised of polar amino acid residues. These findings are particularly relevant for the design of allosteric modulators of ligand-dependent transcription factors. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 19,334 |
This letter studies the joint design of wireless fronthaul and radio access links for the downlink of a cloud radio access network (C-RAN). In a C-RAN, high spectral efficiency can be achieved by migrating the baseband processing functionalities to a baseband processing unit (BBU). However, due to the increased system cost, the size of cluster should be kept relatively small, and hence the spectral efficiency performance tends to be limited by the impact of inter-cluster interference signals. This letter tackles the problem of jointly optimizing the fronthaul and access links across multiple clusters with the goal of maximizing the sum-rate of all the user equipments belonging to the clusters while satisfying the power constraints at the BBUs and remote radio heads. Via numerical results, the effectiveness of the proposed algorithm is confirmed. | Coordinated signal processing can obtain a huge transmission gain for Fog Radio Access Networks (F-RANs). However, integrating into large scale, it will lead to high computation complexity in channel estimation and spectral efficiency loss in transmission performance. Thus, a joint cluster formation and channel estimation scheme is proposed in this paper. Considering research remote radio heads (RRHs) centred serving scheme, a coalition game is formulated in order to maximize the spectral efficiency of cooperative RRHs under the conditions of balancing the data rate and the cost of channel estimation. As the cost influences to the necessary consumption of training length and estimation error. Particularly, an iterative semi-blind channel estimation and symbol detection approach is designed by expectation maximization algorithm, where the channel estimation process is initialized by subspace method with lower pilot length. Finally, the simulation results show that a stable cluster formation is established by our proposed coalition game method and it outperforms compared with full coordinated schemes. | The RNA chaperone Hfq is a key player in small RNA (sRNA)-mediated regulation of target mRNAs in many bacteria. The absence of this protein causes pleiotropic phenotypes such as impaired stress regulation and, occasionally, loss of virulence. Hfq promotes rapid sRNA-target mRNA base pairing to allow for fast, adaptive responses. For this to happen, sRNAs and/or mRNAs must be bound by Hfq. However, when the intra- or extracellular environment changes, so does the intracellular RNA pool, and this, in turn, requires a correspondingly rapid change in the pool of Hfq-bound RNAs. Biochemical studies have suggested tight binding of Hfq to many RNAs, indicating very slow dissociation rates. In contrast, the changing pool of binding-competent RNAs must compete for access to this helper protein in a minute time frame (known response time for regulation). How rapid exchange of RNAs on Hfq in vivo can be reconciled with biochemically stable and very slowly dissociating Hfq-RNA complexes is the topic of this review. Several recent reports suggest that the time scale discrepancy can be resolved by an “active cycling” model: rapid exchange of RNAs on Hfq is not limited by slow intrinsic dissociation rates, but is driven by the concentration of free RNA. Thus, transient binding of competitor RNA to Hfq-RNA complexes increases cycling rates and solves the strong binding/high turnover paradox. | eng_Latn | 19,335 |
In this article, some extremal problems are studied between the super-Cartan domain of the first type and the unit ball. | In this paper we construct a new algorithmic method for finding Caratheodory extremal maps for some balanced domains including complex ellipsoids. | ABSTRACTUNC-45A is an ubiquitously expressed protein highly conserved throughout evolution. Most of what we currently know about UNC-45A pertains to its role as a regulator of the actomyosin system... | eng_Latn | 19,336 |
In molecular communication, the heavy tail nature of molecular signals causes inter-symbol interference (ISI). Because of this, it is difficult to decrease symbol periods and achieve high data rate. As a probable solution for ISI mitigation, enzymes were proposed to be used since they are capable of degrading ISI molecules without deteriorating the molecular communication. While most prior work has assumed an infinite amount of enzymes deployed around the channel, from a resource perspective, it is more efficient to deploy a limited amount of enzymes at particular locations and structures. This paper considers carrying out such deployment at two structures-around the receiver (Rx) and#x002F;or the transmitter (Tx) site. For both of the deployment scenarios, channels with different system environment parameters, Tx-to-Rx distance, size of enzyme area, and symbol period, are compared with each other for analyzing an optimized system environment for ISI mitigation when a limited amount of enzymes are available. | The particle motion in diffusion-based molecular communication systems is typically modeled by using Brownian processes. In particular, this model is used to characterize the propagation of signal molecules after their release from the transmitter. This motion cannot include directionality in the propagating signal and translates into omnidirectional broadcast communications. In order to make such molecular communications system suitable for supporting communications protocols at the molecular scales, we propose to improve the receiver capabilities by introducing a form of directionality while receiving biological signals. Inspired by the directionality introduced in electromagnetic communications by means of directional antennas, we designed a nanomachine receiver having directionality properties. Our aim is to increase the average concentration of signal molecules, also referred to as carriers, in the area around the receiver surface. In this way, it is possible to increase the signal strength at the receiver. For this purpose, we propose to use a purely reflecting shell to be placed at a configurable distance from the receiver surface. The shape of the shell can be modeled as either a spherical cap or a cylinder with an empty basis. The presence of this surface causes a number of signal molecules to remain trapped in a region close to the receiver surface for a sufficiently long time. In this way, the probability of assimilating additional carriers by the compliant receptors present on the receiver surface increases. By means of an extensive simulation campaign, we identified the most suitable configuration able to provide a significant advantage with respect to those not adopting the proposed solution. The resulting approach can be regarded as an enabler of protocols for diffusive molecular communications taking advantage of directionality properties at the receiver site. It can result in an increased communication range or in improved capabilities of discriminating signals of coexisting molecular communication systems. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 19,337 |
The primary structure of proteins consists of a linear chain of amino acids that can vary in length. Proteins fold, under the influence of several chemical and physical factors, into their 3D structures, which determine their biological functions and properties. Misfolding occurs when the protein folds into a 3D structure that does not represent its native structure, which can lead to diseases. Due to the importance of this problem and since laboratory techniques are not always feasible, computational methods for characterizing protein structures have been proposed. In this paper, we present a particle swarm optimization (PSO) based algorithm for predicting protein structures in the 3D hydrophobic polar model. Starting from a small set of candidate solutions, our algorithm efficiently explores the search space and returns 3D protein structures with minimal energy. To test our algorithm, we used two sets of benchmark sequences of different lengths and compared our results to published results. Our algorithm performs better than previous algorithms by finding lower energy structures or by performing fewer numbers of energy evaluations. | Given the amino acid sequence of a protein, predicting its tertiary structure is known as the protein folding problem. This problem has been widely studied under the HP model in which each amino acid is classified, based on its hydrophobicity, as an H (hydrophobic or non-polar) or a P (hydrophilic or polar). Conformation of a protein in the HP model is embedded as a self-avoiding walk in either a two-dimensional or a three-dimensional lattice. The protein folding problem in the HP model is to find a lowest energy conformation. This problem is known to be NP-hard in both two-dimensional and three-dimensional square lattices. In this paper, we present an efficient genetic algorithm for the protein folding problem under the HP model in the two-dimensional square lattice. A special feature of this algorithm is its usage of secondary structures, that the algorithm evolves, as building blocks for the conformation. Experimental results on benchmark sequences show that the algorithm performs very well against existing evolutionary algorithms and Monte Carlo algorithms. | This paper has been withdrawn by the author due to a crucial mistakes. | eng_Latn | 19,338 |
A 17 amino acid peptide containing the arginine-rich region of the HIV Rev protein binds specifically to Rev response element (RRE) RNA. Even though it is highly charged, the peptide forms an alpha helix in solution, but only when its N- and C-termini are modified to provide favorable electrostatic interactions with the helix macrodipole. Binding affinity for IIB RNA (the primary binding site within the RRE) increases with alpha helix content, whereas nonspecific binding affinity is independent of helix content. Binding of mutant peptides demonstrates that one threonine, one asparagine, and four arginine side chains are important for sequence-specific recognition. Transactivation of the HIV LTR using Tat-Rev peptide hybrids and the RRE IIB site indicates that the peptide adopts an alpha-helical conformation in vivo. The results suggest that interactions with the RNA backbone may help to orient the alpha helix in the major groove of RNA. | Proteins are uniquely capable of identifying targets with unparalleled selectivity, but, in addition to the precision of the binding phenomenon, nature has the ability to find its targets exceptionally quickly. Transcription factors for instance can bind to a specific sequence of nucleic acids from a soup of similar, but not identical DNA strands, on a timescale of seconds. This is only possible with the enhanced kinetics provided for by a natively disordered structure, where protein folding and binding are cooperative processes. The secondary structures of many proteins are disordered under physiological conditions. Subsequently, the disordered structures fold into ordered structures only when they bind to their specific targets. Induced folding of the protein has two key biological advantages. First, flexible unstructured domains can result in an intrinsic plasticity that allows them to accommodate targets of various size and shape. And, second, the dynamics of this folding process can result in enhanced binding kinetics. Several groups have hypothesized the acceleration of binding kinetics is due to induced folding where a “fly-casting” effect has been shown to break the diffusion-limited rate of binding. This review describes experimental results in rationally designed peptide systems where the folding is coupled to amphiphilicity and biomolecular activity. | Blunt trauma abdomen rarely leads to gastrointestinal injury in children and isolated gastric rupture is even rarer presentation. We are reporting a case of isolated gastric rupture after fall from height in a three year old male child. | eng_Latn | 19,339 |
A generalized ADK (Ammosov–Delone–Krainov) theory for ionization of open-shell atoms is compared to ionization experiments performed on the transition metal atoms V, Ni, Pd, Ta and Nb. Our theory is found to be in good agreement for V, Ni, Pd and Ta, whereas conventional ADK theory overestimates ionization by orders of magnitude. The key to understanding the observed ionization reduction is the angular momentum barrier. Our analysis shows that the determination of the angular momentum barrier in open-shell atoms is nontrivial. The Stark shift is identified as the second dominant effect responsible for ionization suppression. Finally, these two effects cannot explain the Nb data. An analysis of the electron spins suggests that Pauli blocking might be responsible for the suppression of tunnelling in Nb. | Numerically determined ionization rates for the field ionization of atomic hydrogen in strong and short laser pulses are presented. The laser pulse intensity reaches the so-called ``barrier-suppression ionization'' regime where field ionization occurs within a few half laser cycles. Comparison of our numerical results with analytical theories frequently used shows poor agreement. An empirical formula for the ``barrier-suppression ionization'' rate is presented. This rate reproduces very well the course of the numerically determined ground-state populations for laser pulses with different length, shape, amplitude, and frequency. | Arginine kinase plays an important role in the cellular energy metabolism of invertebrates. Dimeric arginine kinase (dAK) is unique in some marine invertebrates. The effects of Zn 21 on the unfolding and aggregation of dAK from the sea cucumber Stichopus japonicus were investigated. Our results indicated that Zn 21 caused dAK inactivation accompanied by conformational unfolding, the exposure of hydrophobic surface, and aggregation. Kinetic studies showed the inactivation and unfolding of dAK followed biphasic kinetic courses. Zn 21 can affect unfolding and refolding of dAK by trapping the reversible intermediate. Our study provides important information regarding the effect of Zn 21 on | eng_Latn | 19,340 |
Proteins are large, complex molecules with crucial roles in the functioning of living organisms. Understanding the underlying mechanisms by which proteins achieve their structures and substructures, as well as those involved in the conformational transitions may contribute to a deeper comprehension of the involved biological processes. This paper investigates a new machine learning perspective upon analyzing protein conformational transitions and introduces a new formalization for the problem, with the more general goal of uncovering interesting patterns in protein conformational transitions. This study represents the starting point of a research which is being conducted in order to obtain a better comprehension of proteins’ structures and, implicitly, functions, by investigating computational intelligence methods for analyzing and deducing proteins conformational transitions. | To determine the 3D conformation of proteins is a necessity to understand their functions or interactions with other molecules. It is commonly admitted that, when proteins fold from their primary linear structures to their final 3D conformations, they tend to choose the ones that minimize their free energy. To find the 3D conformation of a protein knowing its amino acid sequence, bioinformaticians use various models of different resolutions and artificial intelligence tools, as the protein folding prediction problem is a NP complete one. More precisely, to determine the backbone structure of the protein using the low resolution models (2D HP square and 3D HP cubic), by finding the conformation that minimize free energy, is intractable exactly. Both the proof of NP-completeness and the 2D prediction consider that acceptable conformations have to satisfy a self-avoiding walk (SAW) requirement, as two different amino acids cannot occupy a same position in the lattice. It is shown in this document that the SAW requirement considered when proving NP-completeness is different from the SAW requirement used in various prediction programs, and that they are different from the real biological requirement. Indeed, the proof of NP completeness and the predictions in silico consider conformations that are not possible in practice. Consequences of this fact are investigated in this research work. | We report enhancement of the mechanical stability of graphene through a one-step method to disperse gold nanoparticles on the pristine graphene without any added agent. | eng_Latn | 19,341 |
This Review discusses the potential usefulness of the worm Caenorhabditis elegans as a model organism for chemists interested in studying living systems. C. elegans, a 1 mm long roundworm, is a popular model organism in almost all areas of modern biology. The worm has several features that make it attractive for biology: it is small (<1000 cells), transparent, and genetically tractable. Despite its simplicity, the worm exhibits complex phenotypes associated with multicellularity: the worm has differentiated cells and organs, it ages and has a well-defined lifespan, and it is capable of learning and remembering. This Review argues that the balance between simplicity and complexity in the worm will make it a useful tool in determining the relationship between molecular-scale phenomena and organism-level phenomena, such as aging, behavior, cognition, and disease. Following an introduction to worm biology, the Review provides examples of current research with C. elegans that is chemically relevant. It also describes tools-biological, chemical, and physical-that are available to researchers studying the worm. | With respect to their high abundances, their role as intermediaries between microorganisms and higher trophic levels, and their ubiquitous occurrence in all habitats, nematodes are of strong potential interest as environmental indicators. Ecotoxicological methods to evaluate the risk of anthropogenic pollutants on ecosystems require both in vitro and in vivo toxicity tests to investigate either mechanisms or pathways of toxicity and to set accurate toxicity thresholds. For this, the interest in nematodes as model organisms in ecotoxicology increased over the past few decades and existing appropriate experimental methods are reviewed in this manuscript. An overview of the various existing ecotoxicological tools for nematodes, ranging from molecular laboratory methods to experimental model ecosystem approaches, and their role as indicator organisms is given. The reviewed studies, approaches that range from species-based to community-based methods, reveal exciting possibilities for the future use of nematodes in ecotoxicological studies. Suitable ecotoxicological tools and ecological indices for nematodes should be integrated in weight-of-evidence approaches for assessing the ecological risk of contamination. | Networks of coupled dynamical systems have been used to model biological oscillators1,2,3,4, Josephson junction arrays5,6, excitable media7, neural networks8,9,10, spatial games11, genetic control networks12 and many other self-organizing systems. Ordinarily, the connection topology is assumed to be either completely regular or completely random. But many biological, technological and social networks lie somewhere between these two extremes. Here we explore simple models of networks that can be tuned through this middle ground: regular networks ‘rewired’ to introduce increasing amounts of disorder. We find that these systems can be highly clustered, like regular lattices, yet have small characteristic path lengths, like random graphs. We call them ‘small-world’ networks, by analogy with the small-world phenomenon13,14 (popularly known as six degrees of separation15). The neural network of the worm Caenorhabditis elegans, the power grid of the western United States, and the collaboration graph of film actors are shown to be small-world networks. Models of dynamical systems with small-world coupling display enhanced signal-propagation speed, computational power, and synchronizability. In particular, infectious diseases spread more easily in small-world networks than in regular lattices. | eng_Latn | 19,342 |
Motivation: Learning-based model quality assessment programs have been quite successful at discriminating between high-and low-quality protein structures. Here, we show that it is possible to improve this performance significantly by restricting the learning space to a specific context, in this case membrane proteins. Since these are among the most important structures from a pharmaceutical point-of-view, it is particularly interesting to resolve local model quality for regions corresponding, e.g. to binding sites. ::: ::: Results: Our new ProQM method uses a support vector machine with a combination of general and membrane protein-specific features. For the transmembrane region, ProQM clearly outperforms all methods developed for generic proteins, and it does so while maintaining performance for extra-membrane domains; in this region it is only matched by ProQres. The predictor is shown to accurately predict quality both on the global and local level when applied to GPCR models, and clearly outperforms consensus-based scoring. Finally, the combination of ProQM and the Rosetta low-resolution energy function achieve a 7-fold enrichment in selection of near-native structural models, at very limited computational cost. ::: ::: Availability: ProQM is available as a server at +proqm.cbr.su.se+. ::: ::: Contact: [email protected] ::: ::: Supplementary information: Supplementary data are available at Bioinformatics online. | Fast and accurate side-chain conformation prediction is important for homology modeling, ab initio protein structure prediction, and protein design applications. Many methods have been presented, although only a few computer programs are publicly available. The SCWRL program is one such method and is widely used because of its speed, accuracy, and ease of use. A new algorithm for SCWRL is presented that uses results from graph theory to solve the combinatorial problem encountered in the side-chain prediction problem. In this method, side chains are represented as vertices in an undirected graph. Any two residues that have rotamers with nonzero interaction energies are considered to have an edge in the graph. The resulting graph can be partitioned into connected subgraphs with no edges between them. These subgraphs can in turn be broken into biconnected components, which are graphs that cannot be disconnected by removal of a single vertex. The combinatorial problem is reduced to finding the minimum energy of these small biconnected components and combining the results to identify the global minimum energy conformation. This algorithm is able to complete predictions on a set of 180 proteins with 34342 side chains in <7 min of computer time. The total chi(1) and chi(1 + 2) dihedral angle accuracies are 82.6% and 73.7% using a simple energy function based on the backbone-dependent rotamer library and a linear repulsive steric energy. The new algorithm will allow for use of SCWRL in more demanding applications such as sequence design and ab initio structure prediction, as well addition of a more complex energy function and conformational flexibility, leading to increased accuracy. | Perfect Quantum Cloning Machines (QCM) would allow to use quantum nonlocality for arbitrary fast signaling. However perfect QCM cannot exist. We derive a bound on the fidelity of QCM compatible with the no-signaling constraint. This bound equals the fidelity of the Bu\v{z}ek-Hillery QCM. | eng_Latn | 19,343 |
Biophysics encompasses many disciplines, and so transcends the knowledge and skills of the individual student; its instruction therefore provides formidable challenges. This paper describes educational materials that were developed by the author and have been used successfully in an interdisciplinary course on biophysics, taken by undergraduates from a variety of disciplines. Projects were devised on topics that ranged from x-ray diffraction to the Hodgkin–Huxley equations. They are team-based and strongly encourage collaboration. Extensive use is made of software, written in Python/SciPy, which was modified by students to explore a large range of phenomena. This software can also be used in lectures, in the teaching of more traditional biophysics courses, and in research. | Proteins need to be unfolded when translocated through the pores in mitochondrial and other cellular membranes. Knotted proteins, however, might get stuck during this process, jamming the pore, since the diameter of the pore is smaller than the size of maximally tightened knot. The jamming probability dramatically increases as the magnitude of the driving force exceeds a critical value, Fc. In this numerical study, we show that for deep knots Fc lies below the force range over which molecular import motors operate, which suggest that in these cases the knots will tighten and block the pores. Next, we show how such topological traps might be prevented by using a pulling protocol of a repetitive, on-off character. Such a repetitive pulling is biologically relevant, since the mitochondrial import motor, like other molecular motors transforms chemical energy into directed motions via nucleotide-hydrolysis-mediated conformational changes, which are cyclic in character. | Berzelius failed to make use of Faraday's electrochemical laws in his laborious determination of equivalent weights. | eng_Latn | 19,344 |
Imaging of subcellular events has been key to recent advances in the basic knowledge base as well as drug discovery for disease states such as cancer. In a snowball effect, advances in imaging have spurred new investigations, which have increased the demand for new technologies. The study of cell division serves as an example of this cycle. Here, application of spinning disk confocal technology to the study of cell division is discussed. While these studies have increased understanding of fundamental mechanisms in several mitotic events, new imaging technologies in the future will unlock more secrets of cell biology. Curr. Protocol. Cytom. 43:12.11.1-12.11.13. © 2008 by John Wiley & Sons, Inc. ::: ::: ::: Keywords: ::: ::: confocal imaging; ::: live cell imaging; ::: mitosis; ::: cell division; ::: microtubule; ::: kinetochore; ::: chromosome condensation; ::: cytokinesis | The power of fluorescence microscopy to study cellular structures and macromolecular complexes spans a wide range of size scales, from studies of cell behavior and function in physiological 3D environments to understanding the molecular architecture of organelles. At each length scale, the challenge in 3D imaging is to extract the most spatial and temporal resolution possible while limiting photodamage/bleaching to living cells. Several advances in 3D fluorescence microscopy now offer higher resolution, improved speed, and reduced photobleaching relative to traditional point-scanning microscopy methods. We discuss a few specific microscopy modalities that we believe will be particularly advantageous in imaging cells and subcellular structures in physiologically relevant 3D environments. | Berzelius failed to make use of Faraday's electrochemical laws in his laborious determination of equivalent weights. | eng_Latn | 19,345 |
We developed a new formulation and derived a set of equations for two-time correlation functions in discrete state space for general Markov chains. Numerical solutions of these equations lead to exact results of correlation functions, which is more efficient and accurate for complex systems than normal Gillespie simulations. The formalism is applied to two simple systems as examples: a two state system and self-regulators with results compared with Monte Carlo simulations and mean-field theory. For self-regulators, from non-adiabatic to adiabatic regimes, we observed both monotonic and turnover kinetic behavior of response time, which can be can tested by experiments. | Gene expression is inherently stochastic; precise gene regulation by transcription factors is important for cell-fate determination. Many transcription factors regulate their own expression, suggesting that autoregulation counters intrinsic stochasticity in gene expression. Using a new strategy, cotranslational activation by cleavage (CoTrAC), we probed the stochastic expression dynamics of cI, which encodes the bacteriophage λ repressor CI, a fate-determining transcription factor. CI concentration fluctuations influence both lysogenic stability and induction of bacteriophage λ. We found that the intrinsic stochasticity in cI expression was largely determined by CI expression level irrespective of autoregulation. Furthermore, extrinsic, cell-to-cell variation was primarily responsible for CI concentration fluctuations, and negative autoregulation minimized CI concentration heterogeneity by counteracting extrinsic noise and introducing memory. This quantitative study of transcription factor expression dynamics sheds light on the mechanisms cells use to control noise in gene regulatory networks. | Berzelius failed to make use of Faraday's electrochemical laws in his laborious determination of equivalent weights. | eng_Latn | 19,346 |
The popular model-free approach to analyze NMR relaxation measurements has been examined using artificial amide 15N relaxation data sets generated from a 10 nanosecond molecular dynamics trajectory of a dihydrofolate reductase ternary complex in explicit water. With access to a detailed picture of the underlying internal motions, the efficacy of model-free analysis and impact of model selection protocols on the interpretation of NMR data can be studied. In the limit of uncorrelated global tumbling and internal motions, fitting the relaxation data to the model-free models can recover a significant amount of quantitative information on the internal dynamics. Despite a slight overestimation, the generalized order parameter is quite accurately determined. However, the model-free analysis appears to be insensitive to the presence of nanosecond time scale motions with relatively small magnitude. For such cases, the effective correlation time can be significantly underestimated. As a result, proteins appear to be more rigid than they really are. The model selection protocols have a major impact on the information one can reliably obtain. The commonly employed protocol based on step-up hypothesis testing has severe drawbacks of oversimplification and underfitting. The consequences are that the order parameter is more severely overestimated and the correlation time more severely underestimated. Instead, model selection based on Bayesian Information Criteria (BIC), recently introduced to the model-free analysis by d'Auvergne and Gooley (2003), provides a better balance between bias and variance. More appropriate models can be selected, leading to improved estimate of both the order parameter and correlation time. In addition, the computational cost is significantly reduced and subjective parameters such as the significance level are unnecessary. | Potential Functions. Dynamical Simulation Methods. Thermodynamic Methods. Atom and Sidechain Motions. Rigid-Body Motions. Larger-Scale Motions. Solvent Influence on Protein Dynamics. Thermodynamic Aspects. Experimental Comparisons and Analysis. Concluding Discussion. References. Index. | It is proved, by using topological properties, that when a group automorphism of a locally compact totally disconnected group is ergodic under the Haar measure, the group is compact. The result is an answer for Halmos's question that has remained open for the totally disconnected case. | eng_Latn | 19,347 |
Time-series profiles of gene expression generated by DNA microarrays possess sufficient information for building dynamic models of transcriptional behavior. This, however, requires properly designed experiments and sufficient independent data to validate such models. Here we report the use of AutoRegressive with eXogenous input (ARX) models to fit dynamic gene expression data obtained by subjecting cultures of the photosynthetic bacterium Synechocystis PCC6803 to consecutive light-to-dark transitions. Autoregressive with exogenous input models of appropriate complexity were selected by applying Akaike's information criterion (AIC) such as to maximize agreement between model predictions with experimental data without overfitting. These models were subsequently used to design the experimental profile of an optimal validating data set. Predictions from these models were tested in a second experiment and were found to match well with the validation data. Additionally, the models with the least error in predicting the expression profiles of the validation data set exactly match the model complexity predicted by AIC. Such models offer insights into cellular responses to environmental conditions and form the basis for hypothesizing and quantifying relationships that are presently poorly understood at the level of fundamental mechanisms. | We use linear Gaussian state-space models to analyse time-course gene expression data of yeast. They are modelled to be generated from hidden state variables in a system. To identify the system, we estimate parameters of the model by EM algorithm and determine the dimension of the state variable by BIC. | It is proved, by using topological properties, that when a group automorphism of a locally compact totally disconnected group is ergodic under the Haar measure, the group is compact. The result is an answer for Halmos's question that has remained open for the totally disconnected case. | eng_Latn | 19,348 |
The equilibrium properties of solvated Cu,Zn superoxide dismutase have been sampled in the isothermal-isobaric ensemble at six different temperatures, namely at T=80, 130, 200, 225, 250, and 300 K. Molecular dynamics simulations covering the same range of temperatures have been also carried out for the protein in vacuo. Evaluation of the Debye–Waller factors as a function of temperature indicates that the “glasslike” transition, experimentally observed at approximately 200 K by neutron scattering experiments, is well reproduced when the protein is simulated in the presence of water solvent whereas the simulations without solvent are not able to reproduce the experimental results. Analysis of anharmonicity and anisotropy of the atomic motions indicates that these parameters are good indicators for the occurrence of the transition. Analysis of the atomic fluctuations of different protein shells, having different degrees of exposure to the solvent, shows that the transition is driven by the protein atoms bel... | Folded proteins may be regarded as soft active matter under physiological conditions. The densely packed hydrophobic interior, the relatively molten hydrophilic exterior, and the spacer connecting these put together a large number of locally homogeneous regions. For the case of the bovine pancreatic trypsin inhibitor, with the aid of molecular dynamics simulations, we have demonstrated that the kinetics of the relaxation of the internal motions is highly concerted, manifesting the protein's heterogeneity, which may arise from variations in density, local packing, or the local energy landscape. This behavior is characterized in a stretched exponential decay described by an exponent of approximately 0.4 at physiological temperatures. Due to the trapped conformations, configurational entropy becomes smaller, and the associated stretch exponent drops to half of its value below the glass transition range. The temperature dependence of the inverse relaxation time closely follows the Vogel-Tamman-Fulcher expression when the protein is biologically active. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 19,349 |
Cooperative interactions among sensory receptors provide a general mechanism to increase the sensitivity of signal transduction. In particular, bacterial chemotaxis receptors interact cooperatively to produce an ultrasensitive response to chemoeffector concentrations. However, cooperativity between receptors in large macromolecular complexes is necessarily based on local interactions and consequently is fundamentally connected to slowing of receptor-conformational dynamics, which increases intrinsic noise. Therefore, it is not clear whether or under what conditions cooperativity actually increases the precision of the concentration measurement. We explicitly calculate the signal-to-noise ratio (SNR) for sensing a concentration change using a simple, Ising-type model of receptor-receptor interactions, generalized via scaling arguments, and find that the optimal SNR is always achieved by independent receptors. | Juxtacrine signaling is an important class of signaling systems that plays a crucial role in various developmental processes ranging from coordination of differentiation between neighboring cells to guiding axon growth during neurogenesis. Such signaling systems rely on the interaction between receptors on one cell and trans-membrane ligands on the membrane of a neighboring cell. Like other signaling systems, the ability of signal-receiving cells to accurately determine the concentration of ligands, is affected by stochastic diffusion processes. However, it is not clear how restriction of ligand movement to the two-dimensional (2D) cell membrane in juxtacrine signaling affects the accuracy of ligand sensing. In this study, we use a statistical mechanics approach, to show that long integration times, from around one second to several hours, are required to reach high-sensing accuracy (better than 10%). Surprisingly, the accuracy of sensing cannot be significantly improved, neither by increasing the number of receptors above three to five receptors per contact area, nor by increasing the contact area between cells. We show that these results impose stringent constraints on the dynamics of processes relying on juxtacrine signaling systems, such as axon guidance mediated by Ephrins and developmental patterns mediated by the Notch pathway. | The catalytic removal of nitrogen oxides (NOx) from lean-burn exhaust emissions is one of the major challenges in environmental catalysis. Among the NOx emission control technologies, NOx storage/reduction (NSR) is currently regarded as one of the most practical technologies for lean-burn gasoline and diesel vehicles. This review gives a comprehensive overview of NSR technology, including the NSR reaction mechanisms, degradation mechanisms and NSR catalyst developments. The NSR reaction and degradation mechanisms will be addressed based on a typical NSR catalyst such as Pt/BaO/Al2O3, along with the concurrent new NSR catalyst developments for enhancing the NSR performance and alleviating their sulfur poisoning and thermal degradation. | eng_Latn | 19,350 |
The establishment of associations between bivalents from Mus domesticus 2n = 40 spermatocytes is a common phenomenon that shows up during the first prophase of meiotic nuclei. In each nucleus, a seemingly random display of variable size clusters of bivalents in association is observed. These associations originate a particular nuclear architecture and determine the probability of encounters between chromosome domains. Hence, the type of randomness in associations between bivalents has nontrivial consequences. We explore different models for randomness and the associated bivalent probability distributions and find that a simple model based on randomly coloring a subset of vertices of a 6-regular graph provides best agreement with microspreads observations. The notion of randomness is thereby explained in conjunction with the underlying local geometry of the nuclear envelope. | Bifurcation analysis is a central task of the analysis of parameterised high-dimensional dynamical systems that undergo transitions as parameters are changed. To characterise such transitions for models with many unknown parameters is a major challenge for complex, hence more realistic, models in systems biology. Its difficulty rises exponentially with the number of model components. The classical numerical and analytical methods for bifurcation analysis are typically limited to a small number of independent system parameters. To address this limitation we have developed a novel approach to bifurcation analysis called discrete bifurcation analysis, that is based on a suitable discrete abstraction of the given system and employs model checking for discovering critical parameter values, referred to as bifurcation points, for which various kinds of behaviour (equilibrium, cycling) appear or disappear. To describe such behaviour patterns, called phase portraits, we use a hybrid version of a CTL logic augmented with direction formulae. Technically, our approach is grounded in a novel method of parameter synthesis from temporal logic formulae using symbolic model checking and implemented in a new high-performance tool Pithya. Pithya itself implements state-of-the-art parameter synthesis methods. For a given ODE model, it allows to visually explore model behaviour with respect to different parameter values. Moreover, Pithya automatically synthesises parameter values satisfying a given property. Such property can specify various behaviour constraints, e.g., maximal reachable concentration, time ordering of events, characteristics of steady states, the presence of limit cycles, etc. The results can be visualised and explored in a graphical user interface. We demonstrate the method on a case study taken from biology describing the interaction of the tumour suppressor protein pRB and the central transcription factor E2F1. This system represents an important mechanism of a biological switch governing the transition from G1 to S phase in the mammalian cell cycle. In the G1-phase the cell makes an important decision. In high concentration levels, E2F1 activates the phase transition. In low concentration of E2F1, the transition to S-phase is rejected and the cell avoids division. | Although family-owned and managed firms are the predominant form of business organization in the world today, little systematic research exists on these companies. This paper builds upon insights found in the emerging literature on these enterprises and upon our own observations to provide a conceptual framework to better understand these complex organizations. We introduce the concept of the Bivalent Attributes—a unique, inherent feature of an organization that is the source of both advantages and disadvantages— to explain the dynamics of the family firm. | eng_Latn | 19,351 |
Stoichiometric Foundation of Large-Scale Biochemical System Analysis.- Modelling Stochastic Clonal Interference.- Software Verification of Biomolecular Systems.- Kinetic Modelling as a Modern Technology to Explore and Modify Living Cells.- Modelling Gene Assembly in Ciliates.- Towards Molecular Programming - a Personal Report on DNA8 and Molecular Computing.- Molecular Information Theory: Solving the Mysteries of DNA.- Formal Modelling of C. elegans Development. A Scenario-Based Approach.- P Systems with Symport/Antiport Rules. A Survey.- Mathematical Modelling of the Immune System.- The ?-calculus as an ion for Biomolecular Systems.- The Topology of Evolutionary Biology.- Models of Genome Evolution. | This paper proposes the Effective Index, a formal tool to support decision processes in drug discovery. The Effective Index is based on concurrency theory and process calculi to describe incrementally complex biological systems and on Markov process theory to handle quantitative information. A running case study concerning the pathways and the drugs related to hypertension exploits the approach. | Perfect Quantum Cloning Machines (QCM) would allow to use quantum nonlocality for arbitrary fast signaling. However perfect QCM cannot exist. We derive a bound on the fidelity of QCM compatible with the no-signaling constraint. This bound equals the fidelity of the Bu\v{z}ek-Hillery QCM. | eng_Latn | 19,352 |
A problem ubiquitous in almost all scientific areas is escape from a metastable state, or relaxation from one stationary distribution to a new one1. More than a century of studies lead to celebrated theoretical and computational developments such as the transition state theory and reactive flux formulation. Modern transition path sampling and transition path theory focus on an ensemble of trajectories that connect the initial and final states in a state space2, 3. However, it is generally unfeasible to experimentally observe these trajectories in multiple dimensions and compare to theoretical results. Here we report and analyze single cell trajectories of human A549 cells undergoing TGF-β induced epithelial-to-mesenchymal transition (EMT) in a combined morphology and protein texture space obtained through time lapse imaging. From the trajectories we identify parallel reaction paths with corresponding reaction coordinates and quasi-potentials. Studying cell phenotypic transition dynamics will provide testing grounds for nonequilibrium reaction rate theories. | Cells in multicellular organisms switch between distinct cell fates, such as proliferation or differentiation into specialized cell types. Genome-wide gene regulatory networks govern this behavior. Theoretical studies of complex networks suggest that they can exhibit ordered (stable) dynamics, raising the possibility that cell fates may represent high-dimensional attractor states. We used gene expression profiling to show that trajectories of neutrophil differentiation converge to a common state from different directions of a 2773-dimensional gene expression state space, providing the first experimental evidence for a high-dimensional stable attractor that represents a distinct cellular phenotype. | We report enhancement of the mechanical stability of graphene through a one-step method to disperse gold nanoparticles on the pristine graphene without any added agent. | eng_Latn | 19,353 |
We present a new method for computing the spectrum of one-electron Rydberg states of non-hydrogenic atoms in a magnetic field, at constant scaled energy. It is based on a variant of the R-matrix method allowing the computation of many energy levels in a single diagonalization. The results are compared with recently obtained high-resolution experimental spectra of the helium atom. The relation between peaks observed in the Fourier transform of scaled spectra and classical closed orbits is discussed. We show the existence of 'ghost' peaks not corresponding to any closed orbit, and also of peaks existing only in non-hydrogenic spectra, due the scattering of the electron by the ionic core. | The role of atoms and related systems in external fields in the study of the manifestations of classical chaos in quantum systems is reviewed. A major theoretical framework for the interpretation o... | The uptake of various amino acids into Streptomyces hydrogenans grown in chemostatically and turbidostatically controlled steady state cultures has been investigated. A close correlation between transport capacity and the growth rates of the cells was found. As shown by kinetic analysis, the increased transport is due to elevated maximum uptake rates, the apparent Michaelis constants remaining unchanged. Analysis of the unidirectional fluxes of cycloleucine revealed that not only the influx is raised as the growth rate is increased but also the efflux. Hence, the conclusion is drawn that the growth-rate dependent modulation of transport capacity is, at least, partially due to the variation of the concentration of active transport components. Since the cells were grown in the absence of external amino acids the results suggest that amino acid transport into S. hydrogenans is under control of endogenous effectors. | eng_Latn | 19,354 |
The unbinding process of a protein-ligand complex of major biological interest was investigated by means of a computational approach at atomistic classical mechanical level. An energy minimisation-based technique was used to determine the dissociation paths of the system by probing only a relevant set of generalized coordinates. The complex problem was reduced to a low-dimensional scanning along a selected distance between the protein and the ligand. Orientational coordinates of the escaping fragment (the ligand) were also assessed in order to further characterise the unbinding. Solvent effects were accounted for by means of the Poisson–Boltzmann continuum model. The corresponding dissociation time was derived from the calculated barrier height, in compliance with the experimentally reported Arrhenius-like behaviour. The computed results are in good agreement with the available experimental data. | Models for the development and function of germinal centers (GCs) have been so widely discussed in the original literature that they now appear in immunology textbooks. Unfortunately, many of the tenets of these models have not yet been subjected to adequate experimental scrutiny. Indeed, recent studies have called several of their principal assumptions into question. In addition, the term germinal center has been applied to a diverse assortment of focal processes of B cell proliferation and differentiation. This variability might be explained by alterations in the progression of a single textbook GC process. Alternatively, distinct developmental pathways may create unique classes of GCs with specialized functions. | Berzelius failed to make use of Faraday's electrochemical laws in his laborious determination of equivalent weights. | eng_Latn | 19,355 |
Neurons are the workhorses of the nervous system, forming intricate networks to store, process and exchange information. They often connect to many thousands of other cells via intricate branched structures called neurites. This gives neurons their complex tree-like shape, which distinguishes them from many other kinds of cell. However, like all cells, neurons must continually repair and replace their internal components as they become damaged. Neurons also need to be able to produce new components at particular times, for example, when they establish new connections and form memories. But how do neurons ensure that these components are delivered to the right place at the right time? In some cases neurons simply recycle components or make new ones where they are needed, but experiments suggest that they transport other essential components up and down neurites as though on a conveyor belt. Individual parts of a neuron are believed to select certain components they need from those that pass by. But can this system, which is known as the sushi-belt model, distribute material to all parts of neurons despite their complex shapes? Using computational and mathematical modeling, Williams et al. show that this model can indeed account for transport within neurons, but that it also predicts certain tradeoffs. To maintain accurate delivery, neurons must be able to tolerate delays of hours to days for components to be distributed. Neurons can reduce these delays, for example, by manufacturing more components than they need. However, such solutions are costly. Tradeoffs between the speed, accuracy and efficiency of delivery thus limit the ability of neurons to adapt and repair themselves, and may constrain the speed and accuracy with which they can form new connections and memories. In the future, experimental work should reveal whether the relationships predicted by this model apply in real cells. In particular, studies should examine whether neurons with different shapes and roles fine-tune the delivery system to suit their particular needs. For example, some neurons may tolerate long delays to ensure components are delivered to the exactly the right locations, while others may prioritize speedy delivery. | Active transport by microtubule motors has a plethora of crucial roles in eukaryotic cells. Organelles often move bidirectionally, employing both plus-end and minus-end directed motors. Bidirectional motion is widespread and may allow dynamic regulation, error correction and the establishment of polarized organelle distributions. Emerging evidence suggests that motors for both directions are simultaneously present on cellular 'cargo', but that their activity is coordinated so that when plus-end motors are active, minus-end motors are not, and vice versa. Both the dynein cofactor dynactin and the Klarsicht (Klar) protein appear to be important for such coordination. The direction of net transport depends on the balance between plus-end directed and minus-end directed motion. In several model systems, factors crucial for setting this balance have now been identified, setting the stage for a molecular dissection of the underlying regulatory mechanisms. These analyses will likely provide insight into motor cooperation in general. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 19,356 |
As a first approximation of immune-mediated within-host parasite dynamics we can consider the immune response as a predator, with the parasite as its prey. In the ecological literature of predator–prey interactions there are a number of different functional responses used to describe how a predator reproduces in response to consuming prey. Until recently most of the models of the immune system that have taken a predator–prey approach have used simple mass action dynamics to capture the interaction between the immune response and the parasite. More recently Fenton and Perkins (2010) employed three of the most commonly used prey-dependent functional response terms from the ecological literature. In this paper we make use of a technique from computing science, process algebra, to develop mathematical models. The novelty of the process algebra approach is to allow stochastic models of the population (parasite and immune cells) to be developed from rules of individual cell behaviour. By using this approach in which individual cellular behaviour is captured we have derived a ratio-dependent response similar to that seen in the previous models of immune-mediated parasite dynamics, confirming that, whilst this type of term is controversial in ecological predator–prey models, it is appropriate for models of the immune system. | This paper examines the influence of the Raf Kinase Inhibitor Protein (RKIP) on the Extracellular signal Regulated Kinase (ERK) signalling pathway [5] through modelling in a Markovian process algebra, PEPA [11]. Two models of the system are presented, a reagent-centric view and a pathway-centric view. The models capture functionality at the level of subpathway, rather than at a molecular level. Each model affords a different perspective of the pathway and analysis. We demonstrate the two models to be formally equivalent using the timing-aware bisimulation defined over PEPA models and discuss the biological significance. | In this short note we prove that if X is a separably rationally connected variety over an algebraically closed field of positive characteristic, then H^1(X, O_X)=0. | eng_Latn | 19,357 |
Reaction networks are commonly used to model the evolution of populations of species subject to transformations following an imposed stoichiometry. This paper focuses on the efficient characterisation of dynamical properties of Discrete Reaction Networks (DRNs). DRNs can be seen as modelling the underlying discrete nondeterministic transitions of stochastic models of reactions networks. In that sense, any proof of non-reachability in DRNs directly applies to any concrete stochastic models, independently of kinetics laws and constants. Moreover, if stochastic kinetic rates never vanish, reachability properties are equivalent in the two settings. The analysis of two global dynamical properties of DRNs is addressed: irreducibility, i.e., the ability to reach any discrete state from any other state; and recurrence, i.e., the ability to return to any initial state. Our results consider both the verification of such properties when species are present in a large copy number, and in the general case. The obtained necessary and sufficient conditions involve algebraic conditions on the network reactions which in most cases can be verified using linear programming. Finally, the relationship of DRN irreducibility and recurrence with dynamical properties of stochastic and continuous models of reaction networks is discussed. | We consider stochastically modeled chemical reaction systems with mass-action kinetics and prove that a product-form stationary distribution exists for each closed, irreducible subset of the state space if an analogous deterministically modeled system with mass-action kinetics admits a complex balanced equilibrium. Feinberg's deficiency zero theorem then implies that such a distribution exists so long as the corresponding chemical network is weakly reversible and has a deficiency of zero. The main parameter of the stationary distribution for the stochastically modeled system is a complex balanced equilibrium value for the corresponding deterministically modeled system. We also generalize our main result to some non-mass-action kinetics. | Anthracyclines such as daunorubicin (DNR) generate radical oxygen species (ROS), which account, at least in part, for their cytotoxic effect. We observed that early ceramide generation (within 6-10 min) through neutral sphingomyelinase stimulation was inhibitable by the antioxidants N-acetylcysteine and pyrrolidine dithiocarbamate, which led to a decrease in apoptosis (>95% decrease in DNA fragmentation after 6 h). Furthermore, we observed that DNR triggers the c-Jun N-terminal kinase (JNK) and the transcription factor activated protein-1 through an antioxidant-inhibitable mechanism. Treatment of U937 cells with cell-permeant ceramides induced both an increase in ROS generation and JNK activation, and apoptosis, all of which were antioxidant-sensitive. In conclusion, DNR-triggered apoptosis implicates a ceramide-mediated, ROS-dependent JNK and activated protein-1 activation. | eng_Latn | 19,358 |
We have used one and two dimensional 1H NMR spectroscopy to characterize the binding of a homodimeric thiazole orange dye, 1,1'-(4,4,8,8-tetramethyl-4,8-diaza-undecamethylene)-bis-4- (3-methyl-2,3-dihydro-(benzo-1,3-thiazole)-2-methylidene)-quinolin ium tetraiodide (TOTO), to various double stranded DNA oligonucleotides. TOTO binds strongly to all the oligonucleotides used, but usually more than one complex is observed and exchange between different binding sites broadens the lines in the NMR spectra. Complete precipitation occurs when TOTO is bound to small oligonucleotides. Binding to larger oligonucleotides occurs by bis-intercalation. The 1:1 complex of TOTO with the oligonucleotide d(CCGACTGATGC):d (GCATCAGTCGG) gave only one complex that was shown to be a bis-intercalation in the CTGA:TCAG binding site. The binding to this site was also characterized by studying the TOTO complex with the d(CCGCTGAGC):d(GCTCAGCGG) oligonucleotide. NOE connectivities and molecular modelling were used to characterize the complex. The 1:1 complex of TOTO with the oligonucleotide d(CCGCTAGCG):d(CGCTAGCGG) containing a CTAG:CTAG binding site was similarly characterized by NMR. It was concluded that the binding of TOTO to larger oligonucleotides is site selective with CTAG:CTAG as the preferred binding site. | The sequence dependence of the double-stranded DNA (dsDNA)-binding affinity of TOTO, a thiazole orange dimer that functions as a DNA-intercalating fluorophore, was measured using single-molecule methods. An analysis was performed of the distribution of excited-state lifetimes of single molecules of TOTO intercalated into dsDNA fragments containing four-base pair sequences shown previously to have high affinity for TOTO under conditions used in nuclear magnetic resonance (NMR) spectroscopy. For the current studies, the putative binding sites were located centrally in 30-base pair-long dsDNA fragments in which the remaining sequence was either all poly-AT or poly-GC. The lifetime of TOTO fluorescence when bound to these fragments was entirely determined by the background sequence, i.e. DNA fragments with a poly-AT background predominantly gave a fluorescence lifetime of 1.7 ns, whereas DNA fragments with a poly-GC background gave a lifetime of 2.0 ns, independent of the presence or absence of the putative binding sequence. By performing competitive binding experiments in which these DNA fragments competed for TOTO binding with pure poly-AT fragments and using single-molecule fluorescence methods to determine the number of each type of DNA fragment having a TOTO bound in an equilibrium mixture, the relative binding affinity of each putative binding site was determined. The results of these experiments showed clearly that TOTO has no preference for binding to the putative binding sites over binding poly-AT or poly-GC under the conditions of these measurements. This suggests that there is very little sequence dependence of TOTO binding under conditions that would likely predominate in most biological applications of this intercalating dye. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 19,359 |
In this chapter, we consider Petri net and logical approaches applied to the discrete modelling and analysis of signal transduction processes. First, we give foundations of Petri nets, in particular those that are important for modelling biochemical networks. We describe fundamental properties, such as invariants, boundedness, liveness and reachability. We briefly discuss Petri net extensions employed in the field, allowing for the definition of quantitative models. The relevance of Petri net properties is further complemented and illustrated through the analysis of the signalling pathway of pheromone response in Saccharomyces cerevisiae. As an alternate discrete modelling approach, we introduce the generalised logical approach initiated by Rene Thomas for a dynamic modelling and analysis of gene regulatory networks. We show how this formalism can be applied to the study of main dynamic properties of signal transduction pathways and how logical models can be converted into Petri nets. For both approaches, we provide comprehensive references for further reading and give an overview on most used software tools. We conclude with some prospects related to the discrete modelling of signalling networks. | Mathematical frameworks circumventing the need of mechanistic detail exist to build models of signal transduction networks: graphs, hypergraphs, Boolean Networks, and Petri Nets. Predicting how a signal transduces in a signaling network is essential to understand cellular functions and disease. Different formalisms exist to describe how a signal transduces in a given intracellular signaling network represented in the aforementioned modeling frameworks: elementary signaling modes, T-invariants, extreme pathway analysis, elementary flux modes and simple paths. While these signal transduction formalisms are broadly used in their respective frameworks, few studies have been done emphasizing how these signal transduction methodologies compare or relate to each other. We present an overview of how signal transduction networks have been modelled using graphs, hypergraphs, Boolean Networks, and Petri Nets in the literature. We provide a literary review of the different formalisms for capturing signal transduction in a given model of an intracellular signaling network. We also discuss the existing translations between the different modeling frameworks, and the relationships between their corresponding signal transduction representations that have been described in the literature. Furthermore, as a new formalism of signal transduction, we show how minimal functional routes proposed for signaling networks modeled as Boolean Networks can be captured by computing topological factories, a methodology found in the metabolic networks literature. We further show that in the case of an acyclic B-hypergraph, the definitions are equivalent. In directed graphs, it has been shown that computations of elementary modes via its incidence matrix correspond to computations of simple paths and feedback loops. We show that computing elementary modes based on the incidence matrix of a B-hypergraph fails to capture minimal functional routes. | Berzelius failed to make use of Faraday's electrochemical laws in his laborious determination of equivalent weights. | eng_Latn | 19,360 |
The analysis of bacteria at the single-cell level is essential to characterization of processes in which cellular heterogeneity plays an important role. BACMMAN (bacteria mother machine analysis) is a software allowing fast and reliable automated image analysis of high-throughput 2D or 3D time-series images from experiments using the ‘mother machine’, a very popular microfluidic device allowing biological processes in bacteria to be investigated at the single-cell level. Here, we describe how to use some of the BACMMAN features, including (i) segmentation and tracking of bacteria and intracellular fluorescent spots, (ii) visualization and editing of the results, (iii) configuration of the image-processing pipeline for different datasets and (iv) BACMMAN coupling to data analysis software for visualization and analysis of data subsets with specific properties. Among software specifically dedicated to the analysis of mother machine data, only BACMMAN allows segmentation and tracking of both bacteria and intracellular spots. For a single position, single channel with 1,000 frames (2-GB dataset), image processing takes ~6 min on a regular computer. Numerous implemented algorithms, easy configuration and high modularity ensure wide applicability of the BACMMAN software. BACMMAN software is used to automate image analysis of high-throughput 2D or 3D time-series images from experiments using the ‘mother machine’, a microfluidic device that allows growth and division of single bacterial cells to be followed. | The cloning of green fluorescent protein (GFP) 15 years ago revolutionized cell biology by permitting visualization of a wide range of molecular mechanisms within living cells. Though initially used to make largely qualitative assessments of protein levels and localizations, fluorescence microscopy has since evolved to become highly quantitative and high-throughput. Computational image analysis has catalyzed this evolution, enabling rapid and automated processing of large datasets. Here, we review studies that combine time-lapse fluorescence microscopy and automated image analysis to investigate dynamic events at the single-cell level. We highlight examples where single-cell analysis provides unique mechanistic insights into cellular processes that cannot be otherwise resolved in bulk assays. Additionally, we discuss studies where quantitative microscopy facilitates the assembly of detailed 4D lineages in developing organisms. Finally, we describe recent advances in imaging technology, focusing especially on platforms that allow the simultaneous perturbation and quantitative monitoring of biological systems. | Perfect Quantum Cloning Machines (QCM) would allow to use quantum nonlocality for arbitrary fast signaling. However perfect QCM cannot exist. We derive a bound on the fidelity of QCM compatible with the no-signaling constraint. This bound equals the fidelity of the Bu\v{z}ek-Hillery QCM. | eng_Latn | 19,361 |
Using a popular vertex-based model to describe a spatially disordered planar epithelial monolayer, we examine the relationship between cell shape and mechanical stress at the cell and tissue level. Deriving expressions for stress tensors starting from an energetic formulation of the model, we show that the principal axes of stress for an individual cell align with the principal axes of shape, and we determine the bulk effective tissue pressure when the monolayer is isotropic at the tissue level. Using simulations for a monolayer that is not under peripheral stress, we fit parameters of the model to experimental data for Xenopus embryonic tissue. The model predicts that mechanical interactions can generate mesoscopic patterns within the monolayer that exhibit long-range correlations in cell shape. The model also suggests that the orientation of mechanical and geometric cues for processes such as cell division are likely to be strongly correlated in real epithelia. | The vertex model is a popular framework for modelling tightly packed biological cells, such as confluent epithelia. Cells are described by convex polygons tiling the plane and their equilibrium is found by minimizing a global mechanical energy, with vertex locations treated as degrees of freedom. Drawing on analogies with granular materials, we describe the force network for a localized monolayer and derive the corresponding discrete Airy stress function, expressed for each $N$-sided cell as $N$ scalars defined over kites covering the cell. We show how a torque balance (commonly overlooked in implementations of the vertex model) requires each internal vertex to lie at the orthocentre of the triangle formed by neighbouring edge centroids. Torque balance also places a geometric constraint on the stress in the neighbourhood of cellular trijunctions, and requires cell edges to be orthogonal to the links of a dual network that connect neighbouring cell centres and thereby triangulate the monolayer. We show how the Airy stress function depends on cell shape when a standard energy functional is adopted, and discuss implications for computational implementations of the model. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 19,362 |
Internal nonlinearities within piezoelectric actuators of Atomic Force Microscopes (AFM) still pose a great challenge for practicers in the area of nanotechnology. Especially, when topography of a large scale area is required along with high resolution, traditional scanning protocol will deteriorate the distortion of images. In this paper, a novel block scan and stitching method is proposed to mitigate such phenomena. By dividing the whole area into blocks and integrating them subsequently, creep, hysteresis and thermal drift within images can be reduced largely. Moreover, the whole procedure is executed in an automatic manner without human's intervention. Its feasibility is also verified by real experimental results. | Manipulation of nanoparticles with atomic force microscopes (AFMs) has been under development for a decade and is now well established as a technique for prototyping nanodevices and for other applications. Until now, the manipulation process for particles with sizes of a few nanometers has been very labor intensive. This severely limits the complexity of the structures that can be built. Particle sizes on the order of 10 nm are comparable to the spatial uncertainties associated with AFM operation, and a user in the loop has been needed to compensate for these uncertainties. This paper addresses thermal drift, which is the major cause of errors for AFMs operating in ambient conditions. It is shown that drift can be estimated efficiently by using Kalman filtering techniques. This approach has firm theoretical foundations and is validated by the experimental results presented in this paper. Manipulation of groups of 15-nm particles is demonstrated under program control, without human intervention over a long period of time, in ambient air and at room temperature. Coupled with existing methods for high-level motion planning, the manipulation capabilities introduced here will permit assembling, from the bottom up, nanostructures that are more complex than those being built today with AFMs. Note to Practitioners-Nanomanipulation with scanning probe microscopes (SPMs) has potential applications in nanodevice and system prototyping, or in small-batch production if multitip arrays are used instead of single tips. However, SPM nanomanipulation is still being used primarily in research labs. A major obstacle to its wider use is the labor and time involved in the process. These are largely due to spatial uncertainty in the position of the tip (which is analogous to a robot's end effector) relative to the sample being manipulated. Today, a skilled user is needed to determine where the tip is and to correct manipulation errors due to inaccurate positional estimates. The major cause of this spatial uncertainty is thermal drift between the tip and the sample. At the time scales relevant to manipulation, the drift can reach values comparable to the size of the objects, especially if these are below /spl sim/10 nm. The techniques discussed in this paper compensate for the drift and enable automated manipulation, with associated savings in time and labor, and increased complexity of the resulting structures. | ABSTRACTUNC-45A is an ubiquitously expressed protein highly conserved throughout evolution. Most of what we currently know about UNC-45A pertains to its role as a regulator of the actomyosin system... | eng_Latn | 19,363 |
Nipple viability was retained in 165 breasts undergoing reduction mammaplasty without dermal pedicles--even when 3 quadrants of the breast were excised. This technique adds versatility in shaping the breast and permits resection of the hypertrophied portions of the breast, rather than predetermined segments. It allows one to translocate and reposition the nipple-areola without tension or kinking of the breast parenchyma. It gives the patient esthetically pleasing breasts. | Reduction mammaplasty with nipple-areolar transposition on a medial pedicle was designed as an alternative to amputation and free nipple graft for women with severe mammary hypertrophy. The purpose of this study was to review the viability and sensory outcome of the nipple-areolar complex (NAC) in 72 women (133 breasts) after medial pedicle and inferior pedicle reduction mammaplasty between 1996 and 2000. The medial pedicle was used for 41 women (79 breasts) with moderate to severe mammary hypertrophy. An inferior pedicle was used for 31 women (54 breasts) with mild to moderate mammary hypertrophy. Mean follow-up for all patients was 25 months. Total sensation of the NAC was obtained in 68 of 79 breasts (86%) after medial pedicle reduction mammaplasty and in 50 of 54 breasts (92%) after inferior pedicle reduction mammaplasty. Total viability of the NAC occurred in 74 of 79 breasts (94%) after medial pedicle reduction mammaplasty and in 53 of 54 breasts (98%) after inferior pedicle reduction mammaplasty. Quantitative sensory testing of the NAC using the pressure-specified sensory device demonstrated that static and moving sensory thresholds of the NAC are lowest in the inferior pedicle group followed by the control group and the medial pedicle group. It can be concluded from this study that the medial and inferior pedicle techniques are capable of supporting vascularity and innervation to the NAC. The medial pedicle technique for severe mammary hypertrophy is a good alternative to free nipple grafting. The amount of breast tissue removed does not correlate with sensory outcome for both inferior and medial pedicle techniques. The pressure-specified sensory device is an excellent means of assessing sensory outcome. | Many fundamental biological processes involve moving macromolecules across membranes, through nanopores, in a process called translocation. Such motion is necessary for gene expression and regulation, tissue formation, and viral infection. Furthermore, in recent years nanopore technologies have been developed for single molecule detection of biological and synthetic macromolecules, which have been most notably employed in next generation DNA sequencing devices. Many successful theories have been established, which calculate the entropic barrier required to elongate a chain during translocation. However, these theories are at the level of the translocation coordinate (number of forward steps) and thus lack a clear connection to experiments and simulations. Furthermore, the proper diffusion coefficient for such a coordinate is unclear. In order to address these issues, we propose a center of mass (CM) theory for translocation. We start with the entropic barrier approach and show that the translocation coordinate is equivalent to the center of mass of the chain, providing a direct interpretation of previous theoretical studies. We thus recognize that the appropriate dynamics is given by CM diffusion, and calculate the appropriate diffusion constant (Rouse or Zimm) as the chain translocates. We illustrate our theoretical approach with a planar nanopore geometry and calculate some characteristic dynamical predictions. Our main result is the connection between the translocation coordinate and the chain CM, however, we also find that the translocation time is sped up by 1–2 orders of magnitude if hydrodynamic interactions are present. Our approach can be extended to include the details included in previous translocation theories. Most importantly this work provides a direct connection between theoretical approaches and experiments or simulations. SIGNIFICANCE Macromolecule motion through nanopores is critical for many biological processes, and has been recently employed for nucleic acid sequencing. Despite this, direct theoretical understandings of translocation are difficult to evaluate due to the introduction of the translocation coordinate. In this manuscript, we propose a theory for translocation written at the center of mass level of the polymer chain. This theoretical approach is more easily compared to experimental and simulation results, and additionally allows one to accurately account for hydrodynamic interactions on the macromolecule dynamics. | eng_Latn | 19,364 |
Evoked synaptic transmission is dependent on interactions between the calcium sensor Synaptotagmin I and the SNARE complex, comprised of Syntaxin, SNAP-25, and Synaptobrevin. Recent evidence suggests that Snapin may be an important intermediate in this process, through simultaneous interactions of Snapin dimers with SNAP-25 and Synaptotagmin. In support of this model, cultured neurons derived from embryonically lethal Snapin null mutant mice exhibit desynchronized release and a reduced readily releasable vesicle pool. Based on evidence that a dimerization-defective Snapin mutation specifically disrupts priming, Snapin is hypothesized to stabilize primed vesicles by structurally coupling Synaptotagmin and SNAP-25. To explore this model in vivo we examined synaptic transmission in viable, adult C. elegans Snapin (snpn-1) mutants. The kinetics of synaptic transmission were unaffected at snpn-1 mutant neuromuscular junctions (NMJs), but the number of docked, fusion competent vesicles was significantly reduced. However, analyses of snt-1 and snt-1;snpn-1 double mutants suggest that the docking role of SNPN-1 is independent of Synaptotagmin. Based on these results we propose that the primary role of Snapin in C. elegans is to promote vesicle priming, consistent with the stabilization of SNARE complex formation through established interactions with SNAP-25 upstream of the actions of Synaptotagmin in calcium-sensing and endocytosis. | The active zone (AZ) of chemical synapses is a specialized area of the presynaptic bouton in which vesicles fuse with the plasma membrane and release neurotransmitters. Efficient signaling requires synaptic vesicles (SVs) to be recruited, primed, and retained at the AZ, in close proximity to voltage-dependent calcium channels that are activated during presynaptic depolarization. The electron-dense specializations at the AZ might provide a molecular platform for the spatial coordination of these different processes. To investigate this hypothesis, we examined high-resolution three-dimensional models of Caenorhabditis elegans cholinergic neuromuscular junctions generated by electron tomography. First, we found that SVs are interconnected within the bouton by filaments similar to those described in vertebrates. Second, we resolved the three-dimensional structure of the dense projection centered in the AZ. The dense projection is a more complex structure than previously anticipated, with filaments radiating from a core structure that directly contact SVs in the interior of the bouton as well as SVs docked at the plasma membrane. Third, we investigated the functional correlate of these contacts by analyzing mutants disrupting two key AZ proteins: UNC-10/RIM and SYD-2/liprin. In both mutants, the number of contacts between SVs and the dense projection was significantly reduced. Similar to unc-10 mutants, the dependence of SV fusion on extracellular calcium concentration was exacerbated in syd-2 mutants when compared with the wild type. Hence, we propose that the dense projection ensures proper coupling of primed vesicles with calcium signaling by retaining them at the AZ via UNC-10/RIM and SYD-2/liprin-dependent mechanisms. | We report enhancement of the mechanical stability of graphene through a one-step method to disperse gold nanoparticles on the pristine graphene without any added agent. | eng_Latn | 19,365 |
The Cytoskeleton : a practical approach | Fluorescence microscopic analysis of cytoskeletal organization and dynamics, Yu-li-Wang an ultrastructural approach to understanding the cytoskeleton, John H. Hartwig actin filament assembly and organization in vitro, John A. Cooper mapping structural and functional domains in actin-binding proteins, Paul Matsudaira the generation and isolation of mutant actins, R. Kimberley Cook and Peter A. Rubinstein association of cytoskeletal proteins with membranes, Carolie A. Carothers Carraway analysis of microtubule dynamics in vitro, Robley C. Williams, Jr methods for the purification and assay of microtubule-associated motility proteins, Roger D. Sloboda methods for studying the cytoskeleton in yeast, P. Solomon et al studying intermediate filaments, Alberto Domingo et al. | Recent theoretical and experimental work on helically twisted photonic crystal fibres (PCFs) is reviewed. Helical Bloch theory is introduced, including a new formalism based on the tight-binding ap... | eng_Latn | 19,366 |
Incorporating hydrogen in mesoscale models | Abstract Hydrogen embrittlement is a major and longstanding challenge in materials science. Mesoscale mechanical models are currently being developed which are providing new insight into hydrogen-dislocation interactions and the subsequent detrimental effect on ductility and ultimate tensile strength. Here, a review of some recent approaches to incorporating hydrogen within crystal plasticity, discrete dislocation plasticity and cohesive zone models are reviewed. Modelling at this scale bridges the gap between atomistic models and continuum engineering models which will be essential to fully understand hydrogen embrittlement. | AbstractTo understand how cells respond to the nanoscale extracellular environment in vivo, cells from various sources have been cultured on nanoscale patterns fabricated using bottom-up and top-down techniques. Human fetal osteoblasts (hFOBs) and stem cells are some of them and they are known to be overtly responsive to nanoscale topographies – allowing us to investigate the hows and whys of the response in vitro. Information gathered from these in vitro studies could be used to control the cells, i.e. make the stem cells differentiate or retain their characteristics without the use of medium supplements. In this review, hFOB and stem cell responses to nanotopographies are summarized and discussed to shed some light on the influence of patterns on the reactions. Although both types of cells are responsive to nanoscale topographies, the responses are found to be unique to topographical dimension, shape, orientation and the types of cells used. This implies that cellular responses are influenced by multitu... | eng_Latn | 19,367 |
Femtonewton entropic forces can control the formation of protein-mediated DNA loops. | We show that minuscule entropic forces, on the order of 100 fN, can prevent the formation of DNA loops-a ubiquitous means of regulating the expression of genes. We observe a tenfold decrease in the rate of LacI-mediated DNA loop formation when a tension of 200 fN is applied to the substrate DNA, biasing the thermal fluctuations that drive loop formation and breakdown events. Conversely, once looped, the DNA-protein complex is insensitive to applied force. Our measurements are in excellent agreement with a simple polymer model of loop formation in DNA, and show that an antiparallel topology is the preferred LacI-DNA loop conformation for a generic loop-forming construct. | We prove existence of solutions for a class of systems of subelliptic PDEs arising from Mean Field Game systems with H\"ormander diffusion. These results are motivated by the feedback synthesis Mean Field Game solutions and the Nash equilibria of a large class of $N$-player differential games. | eng_Latn | 19,368 |
A MATLAB toolbox for structural kinetic modeling | Summary: Structural kinetic modeling (SKM) enables the analysis of dynamical properties of metabolic networks solely based on topological information and experimental data. Current SKM-based experiments are hampered by the time-intensive process of assigning model parameters and choosing appropriate sampling intervals for Monte-Carlo experiments. We introduce a toolbox for the automatic and efficient construction and evaluation of structural kinetic models (SK models). Quantitative and qualitative analyses of network stability properties are performed in an automated manner. We illustrate the model building and analysis process in detailed example scripts that provide toolbox implementations of previously published literature models. ::: ::: Availability: The source code is freely available for download at http://bioinformatics.uni-potsdam.de/projects/skm. ::: ::: Contact: [email protected] | In gene expression analysis often box plots are required with the individual jittered data overlaid. Two solutions are presented with SAS Statistical Graphics. In SAS 9.2 the box plots have to be constructed with vector statements, in SAS 9.3 a more natural solution is possible using a categorical and a linear x-axis. | eng_Latn | 19,369 |
Self-organizing Mobile Ad Hoc Networks: Spontaneous Clustering at the MAC Layer | We present in this paper a master-slave, self-organized, spontaneous, passive, and dynamic clustering algorithm embedded into the Medium Access Control (MAC) layer for Mobile Ad hoc Networks. Any mobile station gets access to the channel by executing a contention-based mechanism similar to the IEEE 802.11 Standard. However, once it seizes the channel, it establishes a temporary cluster to which closer neighbors can get synchronized. Within each cluster, any infrastructure-based MAC protocol can be executed. Link-level computer simulations have been carried out to show that this approach can remarkably improve the performance of ad hoc networks at the MAC layer. | In the framework of cell structure characterization for predictive oncology, we pro- pose in this paper an unsupervised statistical region based active contour approach in- tegrating an original fractional entropy measure for single channel actin tagged fluo- rescence confocal microscopy image segmentation. Following description of statistical based active contour segmentation and the mathematical definition of the proposed frac- tional entropy descriptor, we demonstrate comparative segmentation results between the proposed approach and standard Shannon's entropy obtained for nuclei segmentation. We show that the unsupervised proposed statistical based approach integrating the frac- tional entropy measure leads to very satisfactory segmentation of the cell nuclei from which shape characterization can be subsequently used for the therapy progress assess- ment. | eng_Latn | 19,370 |
Phospholipid Synthesis in the Squid Giant Axon: Enzymes of Phosphatidylinositol Metabolism | : We examined the properties of several enzymes of phospholipid metabolism in axoplasm extruded from squid giant axons. The following synthetic enzymes, CDP-diglyceride: inositol transferase (EC 2.7.8.11), ATP:diglyceride phosphotransferase, diglyceride kinase (EC 2.7.2.-), and phosphatidylinositol kinase (EC 2.7.1.67), were all present in axoplasm. Phospholipid exchange proteins, which catalyzed the transfer of phosphatidylinositol and phosphatidylcholine between membrane preparations and unilamellar lipid vesicles, were also found. However, we did not find conditions under which the synthesis of CDP-diglyceride, phosphatidyl serine, and phosphatidylinositol-4,5-diphosphate could be measured. Subcellular fractionation by differential centrifugation showed that the axoplasmic inositol transferase and phosphatidylinositol kinase activities were largely “microsomal,” while the diglyceride kinase and exchange protein activities were primarily “cytosolic.” | We attempt quantitative implementation of a previous suggestion that asymmetric charge neutralization of DNA phosphate groups may provide part of the driving force for nucleosome folding. Polyelectrolyte theory can be used to estimate the effective compressive force acting along the length of one side of the DNA surface when a fraction of the phosphate groups are neutralized by histones bound to that side. A standard engineering formula then relates the force to the bending amplitude caused by it. Calculated bending amplitudes are consistent with the curvature of nucleosomal DNA and the overall extent of charge neutralization by the histones. The relation of the model to various aspects of nucleosome folding, including the detailed path of core-particle DNA, is discussed. Several other DNA-protein complexes are listed as examples of possible asymmetric charge-induced bending. | eng_Latn | 19,371 |
Time-dynamic quantization of molecular-genetic, photosynthesis and ecosystem hierarchical levels of the biosphere | Abstract Structural-functional organization of natural biological systems is founded on the principle of evolutionary accumulation of information and division into separate hierarchical levels. Every hierarchical level has its own basic processes with a specific time-dynamic quantization scheme. The relative information entropy representing quantization schemes forms a widely known sequence of generalized divine section numbers. The product of photosynthesis basic processes is free energy shunted off into various energy-transferring compounds. The product of other basic processes is the matter also distributed between compounds of the product. Such an energy-matter distribution shows the same divine values of relative information entropy as the quantization scheme. | This is a phenomenological study of the communication processes around quality in a symphony chorus, addressing the research question, How do the communication processes in which organizational mem... | eng_Latn | 19,372 |
Physiology. Unfolding lipid metabolism. | A transcription factor exhibits dual roles, regulating genes that respond to improperly folded proteins and genes that control lipid synthesis. | Research on morphological control in block copolymers under the following four categories: thermoreversible morphology transitions, discovery of new morphologies, the control of morphology by blending and other control methods, is reviewed | eng_Latn | 19,373 |
SnapShot: Spliceosome Dynamics III | Spliceosomes are multi-megadalton RNA-protein molecular machines that carry out pre-mRNA splicing, that is, the removal of non-coding intervening sequences (introns) from eukaryotic pre-mRNAs and the ligation of neighboring coding regions (exons) to produce mature mRNA for protein biosynthesis on the ribosome. They are the prototypes of dynamic molecular machines, assembling de novo for each splicing event by the stepwise recruitment of subunits on a substrate. | On the basis of the discussion in Chap. 3, the general model of the scheduling problem can be simplified. | kor_Hang | 19,374 |
Bridging Conformational Dynamics and Function Using Single-Molecule Spectroscopy | In a typical structure-function relation study, the primary structure of proteins or nucleic acids is changed by mutagenesis and its functional effect is measured via biochemical means. Single-molecule spectroscopy has begun to give a whole new meaning to the "structure-function relation" by measuring the real-time conformational changes of individual biological macromolecules while they are functioning. This review discusses a few recent examples: untangling internal chemistry and conformational dynamics of a ribozyme, branch migration landscape of a Holliday junction at a single-step resolution, tRNA selection and dynamics in a ribosome, repetitive shuttling and snapback of a helicase, and discrete rotation of an ATP synthase. | Abstract The coordinate conditions usually used to describe the open string and its boundary conditions are intrinsically singular at the boundary. As a result, the boundary conditions are difficult to understand or interpret geometrically. The physical requirement that the variation of the string at the boundary yield a vanishing contribution to the variation of the action may be accomplished by the requirement that the induced metric, in non-singular coordinates, have signature (0, — 1) at the boundary and that the metric be C 1 on the boundary. These geometrically simple by analytically somewhat complicated requirements are equivalent to the usual boundary conditions. Lastly it is shown that the open string is, in a strict sense, a special case of the closed string. Some of the peculiar behavior of characteristic curves on the open string becomes clear in this context. | eng_Latn | 19,375 |
Correction to Mitochondrial ADP/ATP Carrier: Preventing Conformational Changes by Point Mutations Inactivates Nucleotide Transport Activity | Published: April 15, 2016 Table 2. Kinetic Parameters of the ScAnc2p Variants ADP/ATP exchange parameters N-ADP binding ATR binding Vmax ADP (nmol min−1 mg−1) KM ADP (μM) K1/2 (μM) Bmax ATR (pmol/mg) Kd ATR (nM) WT ScAnc2p 87 ± 5 1.5 ± 0.2 1.1 ± 0.2 1010 ± 77 192 ± 25 ScAnc2p 10 ± 1 3.4 ± 0.8 3.4 ± 1.2 NM NM ScAnc2p 12 ± 1 0.31 ± 0.09 6.2 ± 2.1 344 ± 11 89 ± 11 The ADP/ATP exchange was followed at 340 nm with freshly isolated mitochondria. The given values are the means of three to six different experiments. Various concentrations of N-ADP were added to isolated mitochondria (0.5 mg/mL). Various [H]ATR concentrations were incubated with isolated mitochondria (1 mg). BMax ATR is the maximal number of ATR binding sites. Nonmeasurable. Addition/Correction | We consider families of random non-unitary contraction operators defined as deformations of CMV matrices which appear naturally in the study of random quantum walks on trees or lattices. We establish several deterministic and almost sure results about the location and nature of the spectrum of such non-normal operators as a function of their parameters. We relate these results to the analysis of certain random quantum walks, the dynamics of which can be studied by means of iterates of such random non-unitary contraction operators. | eng_Latn | 19,376 |
5-hmC–mediated epigenetic dynamics during postnatal neurodevelopment and aging | DNA methylation in the context of epigenetics occurs on the 5' position of cytosine, which can be further oxidized by enzymes from the Ten-eleven translocation (Tet) family, resulting in 5-hydroxymethylcytosine (5-hmC). In the context of embryonic stem cells, Tet and 5-hmC DNA act in an alternate epigenetic state that regulates epigenetic programming and stem cell differentiation. Here, the authors describe the epigenomic profiling of 5-hmC in mouse and human brain across different time periods during development and aging. | The hypernetted-chain (HNC) approximation is applied to study the critical behavior of a Lennard-Jones mixture. The parameters of the model potential are appropriate to describe a He-Xe mixture in the thermodynamic region where ``gas-gas phase separation'' is known to occur. The locus of points in the temperature-concentration plane where the k\ensuremath{\rightarrow}0 limit of the concentration-concentration structure factor ${S}_{\mathrm{cc}}$(k) diverges, i.e., the spinodal line, is determined through an extrapolation of the HNC results from the region where this integral equation is solvable, toward the phase stability boundary, where the algorithm becomes highly unstable and no solution can be found. The extrapolation is based on a power-law behavior of ${S}_{\mathrm{cc}}$(0) that is verified to hold in the realm of the available results. The critical temperature and concentration so obtained compare quite favorably with the experimental data. | eng_Latn | 19,377 |
Principles of chromatin organization in yeast: relevance of polymer models to describe nuclear organization and dynamics | Nuclear organization can impact on all aspects of the genome life cycle. This organization is thoroughly investigated by advanced imaging and chromosome conformation capture techniques, providing considerable amount of datasets describing the spatial organization of chromosomes. In this review, we will focus on polymer models to describe chromosome statics and dynamics in the yeast Saccharomyces cerevisiae. We suggest that the equilibrium configuration of a polymer chain tethered at both ends and placed in a confined volume is consistent with the current literature, implying that local chromatin interactions play a secondary role in yeast nuclear organization. Future challenges are to reach an integrated multi-scale description of yeast chromosome organization, which is crucially needed to improve our understanding of the regulation of genomic transaction. | The past 20 years has witnessed tremendous progress in our understanding of Parkinson's disease. It is now well established that α-synuclein, a presynaptic neuronal protein, is not only a marker but also an actor of the disease. In this review, we discuss the advances that have been obtained in neuropathology using α-synuclein immunohistochemistry and the role of this protein in the spread of the disease. | eng_Latn | 19,378 |
Tau Pathology in Parkinson's Disease | Tau protein-a member of the microtubule-associated protein family-is a key protein involved in many neurodegenerative diseases. Tau pathology in neurodegenerative diseases is characterized by pathological tau aggregation in neurofibrillary tangles (NFTs). Diseases with this typical pathological feature are called tauopathies. Parkinson's disease (PD) was not initially considered to be a typical tauopathy. However, recent studies have demonstrated increasing evidence of tau pathology in PD. A genome-wide association (GWA) study indicated a potential association between tauopathy and sporadic PD. The aggregation and deposition of tau were also observed in ~50% of PD brains, and it seems to be transported from neuron to neuron. The aggregation of NFTs, the abnormal hyperphosphorylation of tau protein, and the interaction between tau and alpha-synuclein may all contribute to the cell death and poor axonal transport observed in PD and Parkinsonism. | Angular correlation of positron-electron annihilation radiation (ACAR) experiments and positron-lifetime measurements have been performed in a-Si and a-Si:H films as a function of temperature. Positronium formation in microvoids is observed in a-Si:H, but not in a-Si. From the width of the narrow positronium ACAR components we estimate the average diameter of the microvoids to be \ensuremath{\sim}20 A\r{}. A complex temperature dependence of the positron and positronium lifetimes is obtained and is discussed in terms of temperature-dependent positron trapping in various sites and in terms of hydrogen detrapping from dangling bonds. | eng_Latn | 19,379 |
IDENTIFICATION OF TRACEABILITY BARCODE BASED ON PHASE CORRELATION ALGORITHM | In the paper phase correlation algorithm based on Fourier transform is applied to the traceability barcode identification, which is a widely used method of image registration. And there is the rotation-invariant phase correlation algorithm which combines polar coordinate transform with phase correlation, that they can recognize the barcode with partly destroyed and rotated. The paper provides the analysis and simulation for the algorithm using Matlab, the results show that the algorithm has the advantages of good real-time and high performance. And it improves the matching precision and reduces the calculation by optimizing the rotation-invariant phase correlation. | Background ::: Intracellular membrane fusion processes are mediated by the spatial and temporal control of SNARE complex assembly that results in the formation of a four-helical bundle, composed of one vesicle SNARE and three target membrane SNARE polypeptide chains. Syntaxins are essential t-SNAREs and are characterized by an N-terminal Habc domain, a flexible linker region, a coiled-coil or SNARE motif and a membrane anchor. The N-terminal Habc domain fulfills important regulatory functions while the coiled-coil motif, present in all SNAREs, is sufficient for SNARE complex formation, which is thought to drive membrane fusion. | yue_Hant | 19,380 |
Cytochrome c Oxidase on the Crossroads of Transcriptional Regulation and Bioenergetics | Mitochondria are the organelles of eukaryotic cells responsible for the ATP production by means of the electron transfer chain (ETC). Its work is under strict genetic control providing the correct assembly of the enzyme complexes and the interface to adapt the energetic demands of the cell to the environment. These mechanisms are particularly developed in the cells with high energy consumption, like neurons and myocytes. This review summarizes several aspects of the involvement of the ETC complexes in the transcriptional control mechanisms of the neurons and other cells. Their influence on the differentiation of neurons is also discussed. | We introduce the TrixX Conformer Generator (TCG), a novel tool for generating conformational ensembles. The tool addresses especially the requirements of large-scale computer-aided drug design applications using conformer databases. For these, the trade-off between accuracy, i.e. rmsd to biologically active conformers, and database size, i.e. the number of conformers in an ensemble, is of central interest. Based on a tree data structure representing the molecule, conformations are generated incrementally in a best-first-search build-up process employing an internal rmsd clustering. This way TCG builds conformational ensembles of low energy conformers utilizing conformational energy as a scoring function. A crucial parameter is the amount of search space to be covered in the build-up process. This parameter is determined according to an exponential function employing a user-specified quality level as base and an exponent which depends on the molecule’s flexibility. The quality level allows the user to set ... | eng_Latn | 19,381 |
A Modular Synthetic Approach toward Exhaustively Stereodiversified Ligand Libraries | This report describes a modular approach to the synthesis of stereodiversified natural product-like libraries. Monomers 2 and 3 were coupled in parallel by silyl-tethered olefin metathesis to generate all 16 stereoisomers of cis-enediols 1. All 16 stereoisomers were incorporated into chimerae having flanking peptidic segments. These chimerae exhibited a broad range of hydrophobicities, raising the possibility that stereochemical variation might be used to tune the pharmacologic properties of small molecules. | We present a class of relaxed memory models, defined in Coq, parameterised by the chosen permitted local reorderings of reads and writes, and by the visibility of inter- and intra-processor communications through memory (e.g. store atomicity relaxation). We prove results on the required behaviour and placement of memory fences to restore a given model (such as Sequential Consistency) from a weaker one. Based on this class of models we develop a tool, diy, that systematically and automatically generates and runs litmus tests. These tests can be used to explore the behaviour of processor implementations and the behaviour of models, and hence to compare the two against each other. We detail the results of experiments on Power and a model we base on them. | eng_Latn | 19,382 |
Control of coherence among the spins of a single electron and the three nearest neighbor 13C nuclei of a nitrogen-vacancy center in diamond | Individual nuclear spins in diamond can be optically detected through hyperfine couplings with the electron spin of a single nitrogen-vacancy (NV) center; such nuclear spins have outstandingly long coherence times. Among the hyperfine couplings in the NV center, the nearest neighbor 13C nuclear spins have the largest coupling strength. Nearest neighbor 13C nuclear spins have the potential to perform fastest gate operations, providing highest fidelity in quantum computing. Herein, we report on the control of coherences in the NV center where all three nearest neighbor carbons are of the 13C isotope. Coherence among the three and four qubits are generated and analyzed at room temperature. | Nuclear organization can impact on all aspects of the genome life cycle. This organization is thoroughly investigated by advanced imaging and chromosome conformation capture techniques, providing considerable amount of datasets describing the spatial organization of chromosomes. In this review, we will focus on polymer models to describe chromosome statics and dynamics in the yeast Saccharomyces cerevisiae. We suggest that the equilibrium configuration of a polymer chain tethered at both ends and placed in a confined volume is consistent with the current literature, implying that local chromatin interactions play a secondary role in yeast nuclear organization. Future challenges are to reach an integrated multi-scale description of yeast chromosome organization, which is crucially needed to improve our understanding of the regulation of genomic transaction. | eng_Latn | 19,383 |
Chemoenzymatic total synthesis of stagonolide-E | Abstract Asymmetric total synthesis of small ring macrolide stagonolide-E has been described in this communication. The main highlight of our synthetic strategy is the application of ME-DKR (metal enzyme combo dynamic kinetic resolution) reaction, asymmetric reduction with Noyori’s BINAL-H reagent system, stereoselective cross metathesis, and RCM (ring closing metathesis) reaction at a late stage enables us to achieve the synthesis of the target molecule in an efficient way. | ConspectusThe axioms of stereoelectronic theory constitute an atlas to navigate the contours of molecular space. All too rarely lauded, the advent and development of stereoelectronic theory has been one of organic chemistry’s greatest triumphs. Inevitably, however, in the absence of a comprehensive treatise, many of the field’s pioneers do not receive the veneration that they merit. Rather their legacies are the stereoelectronic pillars that persist in teaching and research. This ubiquity continues to afford practitioners of organic chemistry with an abundance of opportunities for creative endeavor in reaction design, in conceiving novel activation modes, in preorganizing intermediates, or in stabilizing productive transition states and products. Antipodal to steric governance, which mitigates destabilizing nonbonding interactions, stereoelectronic control allows well-defined, often complementary, conformations to be populated. Indeed, the prevalence of stabilizing hyperconjugative interactions in biosynt... | eng_Latn | 19,384 |
Neural tube morphogenesis in synthetic 3D microenvironments | Three-dimensional organoid constructs serve as increasingly widespread in vitro models for development and disease modeling. Current approaches to recreate morphogenetic processes in vitro rely on poorly controllable and ill-defined matrices, thereby largely overlooking the contribution of biochemical and biophysical extracellular matrix (ECM) factors in promoting multicellular growth and reorganization. Here, we show how defined synthetic matrices can be used to explore the role of the ECM in the development of complex 3D neuroepithelial cysts that recapitulate key steps in early neurogenesis. We demonstrate how key ECM parameters are involved in specifying cytoskeleton-mediated symmetry-breaking events that ultimately lead to neural tube-like patterning along the dorsal–ventral (DV) axis. Such synthetic materials serve as valuable tools for studying the discrete action of extrinsic factors in organogenesis, and allow for the discovery of relationships between cytoskeletal mechanobiology and morphogenesis. | The DNA sequence of one of the smallest eukaryotic genomes has recently been finished - that of the reduced nucleus, or nucleomorph, of an algal endosymbiont that resides within a cryptomonad host cell. Its sequence promises insights into chloroplast acquisition, the constraints on genome size and the basic workings of eukaryotic cells. | eng_Latn | 19,385 |
Fluorescence correlation spectroscopy and Brownian dynamics simulation of protein diffusion under confinement in lipid cubic phases | The diffusion coefficient of protein lysozyme confined in lipid monoolein cubic phases was measured by fluorescence correlation spectroscopy. From the ratio of the diffusion coefficient of confined lysozyme to the one in a bulk solution, the barrier of confined diffusion was estimated to be about 3–4kBT at 20 °C. The origin of the barrier was investigated using Brownian dynamics simulations with model cubic phase structures based on so-called infinite periodic minimal surfaces. The simulations suggested a structure of the confinement as well as the importance of the hydrodynamic interaction between a particle and walls. | Publisher Summary A variety of disorders of the nervous system results in parkinsonian symptoms. Virtually all of them involve damage to various components of the basal ganglia (BG). This chapter reviews the neuropathologic features of many of these conditions. The chapter focuses on the neuropathologic findings in cases of Parkinson's disease—the prototype condition. Although the presence of Lewy bodies is required to make a diagnosis of sporadic Parkinson's disease, Lewy bodies are encountered in association with a number of other conditions. There are other rare forms of genetically based Parkinson's disease that may or may not demonstrate Lewy body formation. The conjugation of ubiquitin on virtually all such protein aggregates is reviewed and it is suggested that dysfunction of the ubiquitin–proteosome machinery underlies a basic inability to clear specific damaged proteins, leading to their accumulation. | eng_Latn | 19,386 |
Multiple Conformations of RGDW anddRGDW: A Theoretical Study and Comparison with NMR Results | The utility of molecular dynamics simulations in complementing limited NMR data for small peptides is demonstrated by an application to the important cell adhesion peptide Arg-Gly-Asp-Trp (RGDW) and its synthetic analogue, d-Arg-Gly-Asp-Trp (d-RGDW). The results of an earlier NMR study of these peptides were interpreted in terms of a type II‘ β-turn conformation (Kieffer, B.; Mer, G.; Mann, A.; Lefevre, J. F. Int. J. Pept. Protein Res. 1994, 44, 70−79). The present simulations provide additional insight into the solution structure of the RGDW and d-RGDW peptides by identifying extended conformations of both peptides in aqueous solution that are also compatible with the NMR data. The extended conformations have similar values for the NMR observables as the type II‘ β-turn, including the pH titration behavior, coupling constants, ROESY proton distances and pKa values of the Asp side chain and the C-terminal end. Thus it is difficult to distinguish the two conformations by NMR alone. Poisson−Boltzmann contin... | 4 pages.-- PACS numbers: 05.45.Xt, 87.10.+e.-- ArXiv pre-print: http://arxiv.org/abs/nlin.CD/0512009.-- Final full-text version of the paper available at: http://dx.doi.org/10.1103/PhysRevE.73.055202. | eng_Latn | 19,387 |
Identification and Characterization of a Glucagon Receptor from the Goldfish Carassius auratus: Implications for the Evolution of the Ligand Specificity of Glucagon Receptors in Vertebrates | The structural basis of ligand selectivity of G protein-coupled receptors for metabolic hormones has been an area of intense investigation, and yet it remains unresolved. One approach to delineating the mechanism of ligand-receptor interactions is to compare the ligand specificities of receptors expressed in species that emerged at different times within vertebrate evolution. In this paper we describe the isolation, functional, and phylogenetic characterization of the glucagon receptor from the goldfish Carassius auratus (Teleostei, order Cypriniformes), and compare its ligand specificity with that of the homologous rat receptor. Goldfish (gf) glucagon stimulated glucose production in a dose-dependent manner from isolated goldfish hepatocytes, resulting in 5-fold increase at 1 μm. The goldfish glucagon receptor (gfGlucR) shares 56, 51, 50, and 52% amino acid identities with frog Rana tigrina regulosa, mouse, rat, and human glucagon receptors, respectively. In competitive binding experiments, the recombina... | The statistics of rigid-chain polymer conformations is described on the basis of a model of directed self-avoiding walks. The generating functions for the distribution function of a chain in one-, two-, and three-dimensional spaces are constructed. It is shown that the statistics of the conformational states of chains with finite interunit flexural stiffness can differ strongly from Gaussian statistics. If the chain length is comparable to the Kuhn segment length, then the molecule is strongly anisotropic (almost rectilinear), but as the chain length increases, the molecule starts to bend and ultimately coils up. However, since a coil contains extended, almost rectilinear, chain sections, the coil is not truly Gaussian, even though the squared average size of the coil is directly proportional to the chain length. It is shown that under certain conditions the existence of almost rectilinear chain sections results in the appearance of orientational order in the system. | eng_Latn | 19,388 |
Quantum mechanics and high-energy physics | We discuss the phenomenological implications of a recent suggestion that the canonical commutation relations of quantum mechanics should be generalized to be applicable in the high-energy domain. Some evidence is given that this modification could become important around a mass of 106 G-eV typical of partial grand unification schemes. | Quantitative chemoproteomics has recently emerged as an experimental approach to determine protein interaction profiles of small molecules in a given cell line or tissue. In contrast to standard biochemical and biophysical kinase assays, application of this method to kinase inhibitors determines compound binding to endogenously expressed kinases under conditions approximating the physiological situation with regard to the molecular state of the kinase and presence of required cofactors and regulatory proteins. Using a dose-dependent, competition-based experimental design in combination with quantitative mass spectrometry approaches, such as the use of tandem mass tags (TMT) for isobaric labeling described here, allows to rank-order interactions of inhibitors to kinase by binding affinity. | eng_Latn | 19,389 |
Enhancing Undergraduate Chemistry Education with the Online Dynamic ChemWiki Resource | Protonation Heterogeneity Modulates the Ultrafast Photocycle Initiation Dynamics of Phytochrome Cph1. | Dynamically eliciting unobservable information | eng_Latn | 19,390 |
Nature Rev. Mol. Cell Biol. 3, 871–876 (2002) There is an article (November 2002) associated with this correction. Please click here to view it. The author would like to make the following corrections to his article, which includes an amended depiction of Philip Siekevitz's role: Philip Siekevitz was integral to many aspects of the cell biology laboratory at Rockefeller University, guiding many students and postdoctoral fellows and collaborating with George Palade for 20 years. | Compartmentalization of eukaryotic cells into dynamic organelles that exchange material through regulated membrane traffic governs virtually every aspect of cellular physiology including signal transduction, metabolism and transcription. Much has been revealed about the molecular mechanisms that control organelle dynamics and membrane traffic and how these processes are regulated by metabolic, physical and chemical cues. From this emerges the understanding of the integration of specific organellar phenomena within complex, multiscale and nonlinear regulatory networks. In this review, we discuss systematic approaches that revealed remarkable insight into the complexity of these phenomena, including the use of proximity-based proteomics, high-throughput imaging, transcriptomics and computational modeling. We discuss how these methods offer insights to further understand molecular versatility and organelle heterogeneity, phenomena that allow a single organelle population to serve a range of physiological functions. We also detail on how transcriptional circuits drive organelle adaptation, such that organelles may shift their function to better serve distinct differentiation and stress conditions. Thus, organelle dynamics and membrane traffic are functionally heterogeneous and adaptable processes that coordinate with higher-order system behavior to optimize cell function under a range of contexts. Obtaining a comprehensive understanding of organellar phenomena will increasingly require combined use of reductionist and system-based approaches. | Berzelius failed to make use of Faraday's electrochemical laws in his laborious determination of equivalent weights. | eng_Latn | 19,391 |
In this article we review the current status of our understanding of membrane mediated interactions from theory and experiment. Phenomenological mean field and molecular models will be discussed and compared to recent experimental results from dynamical neutron scattering and atomic force microscopy. | Bacteriorhodopsin, a membrane protein with a relative molecular mass of 27,000, is a light driven pump which transports protons across the cell membrane of the halophilic organism Halobacterium salinarum. The chromophore retinal is covalently attached to the protein via a protonated Schiff base. Upon illumination, retinal is isomerized. The Schiff base then releases a proton to the extracellular medium, and is subsequently reprotonated from the cytoplasm. An atomic model for bacteriorhodopsin was first determined by Henderson et al, and has been confirmed and extended by work in a number of laboratories in the last few years. Here we present an atomic model for structural changes involved in the vectorial, light-driven transport of protons by bacteriorhodopsin. A 'switch' mechanism ensures the vectorial nature of pumping. First, retinal unbends, triggered by loss of the Schiff base proton, and second, a protein conformational change occurs. This conformational change, which we have determined by electron crystallography at atomic (3.2 A in-plane and 3.6 A vertical) resolution, is largely localized to helices F and G, and provides an 'opening' of the protein to protons on the cytoplasmic side of the membrane. | I propose to criticize two strands of argument—contractarian and utilitarian—that liberals have put forth in defense of economic coercion, based on the notion of justifiable paternalism. To illustrate my argument, I appeal to the example of forced labor migration, driven by the exigencies of market forces. In particular, the forced migration of a special subset of unemployed workers lacking other means of subsistence (economic refugees) cannot be redeemed paternalistically as freedom or welfare enhancing in the long run. Further, contractarian and utilitarian approaches are normatively incapable of appreciating this fact because the kinds of reasons that they adduce for justifying the long-term freedom-enhancing consequences of forced migration are not ones that would be acceptable to the migrants themselves. I conclude that only a discourse ethical approach, which mandates direct, empathetic communication between would-be migrants and members of potential host communities, captures the full range of reasons that would be acceptable to both migrants and members of these communities. These reasons—appealing both to agency-enhancing communal attachments as well as to agency-enhancing freedom of choice—fully reveals the extent to which a global capitalist system composed of relatively closed national communities coerces the world’s poorest migrants. | eng_Latn | 19,392 |
Polarity orientation of microtubules utilizing a dynein-based gliding assay | The motor protein dynein was introduced into a nanotransport system. We oriented microtubules by their polarity, and immobilized them based on a dynein–microtubule gliding assay system. This system achieved unidirectional transport of kinesin-coated microbeads. In contrast to conventional kinesin-based orientation systems, the dynein-based system allowed the reverse motion of microtubules, resulting in an inversion of the orientation of microtubule polarity and thus reverse transport of kinesin-coated microbeads. This combined kinesin- and dynein-based system constitutes a new means to facilitate the bidirectional orientation of microtubules and transport of cargos in a nanofluidic system. | A highly active fraction of rat liver oligonucleosome DNA has been isolated and studied by means of thermal denaturation after induction by amino acid mixture or hydrocortisone. A considerable redistribution of DNA content has been shown in sucrose gradient fractions during these forms of induction. The changes are revealed in melting temperature, differential melting profile of DNA, isolated from actively transcribed chromatine fractions. Analysis of melting profiles shows changes of GC content of oligonucleosome DNA, suggesting that there are differences in activation during two studied forms of induction. | eng_Latn | 19,393 |
Cellular and viral contributions to maintenance of the SV40-transformed state | 1. ::: ::: A complex type of intercellular contact, requiring cluster formation among three cells or more, is a prerequisite to growth control for a large number of established fibroblast lines. ::: ::: ::: ::: ::: 2. ::: ::: This form of contact occurs at lowest cell densities among cells that synthesize a specific protein that blocks intercellular WGA agglutination. ::: ::: ::: ::: ::: 3. ::: ::: High saturation density cells, lacking this protein, are rapidly agglutinated by WGA. ::: ::: ::: ::: ::: 4. ::: ::: Low saturation density cells, including a line containing SV40 T antigen and the SV40 genome, make this protein, and consequently are agglutinated poorly. ::: ::: ::: ::: ::: 5. ::: ::: The presence of the SV40 genome and SV40 T antigen are not sufficient to guarantee that a cell lines will have a high saturation density or that it will respond well to the WGA agglutinin. | We studied the dynamics of isolated vesicles as well as vesicle interactions in semi-dilute vesicle suspensions subjected to a shear flow. We found that the long-range hydrodynamic interactions between vesicles give rise to strong fluctuations of vesicle shape and inclination angle, , though the functional dependence of and the transition path to tumbling motion is preserved. The dependence of the suspension viscosity on the viscosity ratio between inner and outer fluids, ?, was found to be non-monotonic and surprisingly growing with ? at the fixed outer fluid viscosity for ?<1, at odds with recent predictions made for a dilute suspension of non-interacting vesicles. | eng_Latn | 19,394 |
Decoupled Neural Interfaces using Synthetic Gradients | Distributed optimization of deeply nested systems | Post-Translational Modifications in sperm Proteome: The Chemistry of Proteome diversifications in the Pathophysiology of male factor infertility. | eng_Latn | 19,395 |
Composition fluctuations, chemical exchange, and nuclear relaxation in membranes containing cholesterol | A thermodynamic model of cholesterol-phospholipid complexes is used as a starting point for calculating fluctuations in membranes containing cholesterol and phospholipids. The calculations describe fluctuations in the concentration of complexes formed between cholesterol and phospholipids with longer saturated fatty acid chains. The fluctuations in complex concentrations arise by two distinct mechanisms. In one, the chemical composition of the sample varies from point to point, and the concentration of the complexes varies according to local chemical equilibrium. In the second, the composition remains fixed, and the complexes form and dissociate according to chemical reaction kinetics. In both cases the nuclear resonance frequency of a deuterium labeled phospholipid undergoes fluctuations and line broadening as a consequence of the formation and dissociation of complexes. For a specific ternary lipid mixture at its critical composition, deuterium nuclear resonance line broadening of chain labeled phosphol... | Data on the existence of a specific system regulating the growth, size, and structure of enterobacterial populations are first summarized in terms of the chemical ecology concept formulated by S.S. Shvarts. The role of this system in transgene functioning is described using the example of the lux operon integrated into Escherichia coli. A relatively simple test for estimating such interactions is proposed. | eng_Latn | 19,396 |
Abstract 13212: Extensive Reserve Capacity for the Binding and Movement of Fibrinogen on the Surface of Activated Human Platelets | We have previously imaged fibrinogen binding to its integrin αIIb β3 receptor on activated human platelets through labeling with colloidal gold-ligand conjugates followed by light and/or electron m... | We developed a method for solving the fluorescence equation of radiative transfer in the frequency domain on blockstructured ::: grids. In this way fluorescence light propagation in arbitrarily shaped tissue can be modeled with high ::: accuracy without compromising on the convergence speed of these codes. The block-structure grid generator is ::: developed as a multi-purpose tool that can be used with many numerical schemes. We present results from numerical ::: studies that show that it is possible to resolve curved boundaries with grids that maintain much of the intrinsic structure ::: of Cartesian grids. The natural ordering of this grid allows for simplified algorithms. In simulation studies we found that ::: we can reduce the error in boundary fluence by a factor of five by using a two-level block structured grid. The increase ::: in computational cost is only two-fold. We compare benchmark solutions to results with various levels of refinement, ::: boundary conditions, and different geometries. | eng_Latn | 19,397 |
Function changing mutations in glucocorticoid receptor evolution correlate with their relevance to mode coupling | Nonlinear effects in protein dynamics are expected to play role in function, particularly of allosteric nature, by facilitating energy transfer between vibrational modes. A recently proposed method focusing on the non-Gaussian shape of the configurational population near equilibrium projects this information onto real space in order to identify the aminoacids relevant to function. We here apply this method to three ancestral proteins in glucocorticoid receptor (GR) family and show that the mutations that restrict functional activity during GR evolution correlate significantly with locations that are highlighted by the nonlinear contribution to the near-native configurational distribution. Our findings demonstrate that the analysis of nonlinear effects in protein dynamics can be harnessed into a predictive tool for functional site determination. | In this paper, by using the coefficient mapping from plant to GPC closed-loop system in the IMC structure, the stability conditions for closed-loop system with respect to selection of tuning parameters are derived. Furthermore, some simple conditions described by step response coefficients for tuning parameters which guarantee the stability of the closed-loop system are also obtained. | eng_Latn | 19,398 |
Diverse fragment clustering and water exclusion identify protein hot spots. | Simulated annealing of chemical potential located the highest affinity positions of eight organic probes and water on eight static structures of hen egg white lysozyme (HEWL) in various conformational states. In all HELW conformations, a diverse set of organic probes clustered in the known binding site (hot spot). Fragment clusters at other locations were excluded by tightly-bound waters so that only the hot-spot cluster remained in each case. The location of the hot spot was correctly predicted irrespective of the protein conformation and without accounting for protein flexibility during the simulations. Any one of the static structures could have been used to locate the hot spot. A site on a protein where a diversity of organic probes is calculated to cluster, but where water specifically does not bind, identifies a potential small-molecule binding site or protein–protein interaction hot spot. | Immune cell populations are constantly divided into smaller and smaller subsets defined by newly emerging cellular markers. However, there is a growing awareness of the functional heterogeneities i ... | eng_Latn | 19,399 |
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