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Thermal capillary wave	Thermal capillary wave	Thermal motion is able to produce capillary waves at the molecular scale. At this scale, gravity and hydrodynamics can be neglected, and only the surface tension contribution is relevant. Capillary wave theory (CWT) is a classic account of how thermal fluctuations distort an interface. It starts from some intrinsic surface h(x,y,t) that is distorted. Its energy will be proportional to its area: Est=σ∫dxdy[1+(dhdx)2+(dhdy)2−1]≈σ2∫dxdy[(dhdx)2+(dhdy)2], where the first equality is the area in this (de Monge) representation, and the second applies for small values of the derivatives (surfaces not too rough). The constant of proportionality, σ , is the surface tension.
Thermal capillary wave	Thermal capillary wave	By performing a Fourier analysis treatment, normal modes are easily found. Each contributes an energy proportional to the square of its amplitude; therefore, according to classical statistical mechanics, equipartition holds, and the mean energy of each mode will be kT/2 . Surprisingly, this result leads to a divergent surface (the width of the interface is bound to diverge with its area). This divergence is nevertheless very mild: even for displacements on the order of meters the deviation of the surface is comparable to the size of the molecules. Moreover, the introduction of an external field removes the divergence: the action of gravity is sufficient to keep the width fluctuation on the order of one molecular diameter for areas larger than about 1 mm2 (Ref. 2).
Fundamental matrix (computer vision)	Fundamental matrix (computer vision)	In computer vision, the fundamental matrix F is a 3×3 matrix which relates corresponding points in stereo images. In epipolar geometry, with homogeneous image coordinates, x and x′, of corresponding points in a stereo image pair, Fx describes a line (an epipolar line) on which the corresponding point x′ on the other image must lie. That means, for all pairs of corresponding points holds 0.
Fundamental matrix (computer vision)	Fundamental matrix (computer vision)	Being of rank two and determined only up to scale, the fundamental matrix can be estimated given at least seven point correspondences. Its seven parameters represent the only geometric information about cameras that can be obtained through point correspondences alone. The term "fundamental matrix" was coined by QT Luong in his influential PhD thesis. It is sometimes also referred to as the "bifocal tensor". As a tensor it is a two-point tensor in that it is a bilinear form relating points in distinct coordinate systems. The above relation which defines the fundamental matrix was published in 1992 by both Olivier Faugeras and Richard Hartley. Although H. Christopher Longuet-Higgins' essential matrix satisfies a similar relationship, the essential matrix is a metric object pertaining to calibrated cameras, while the fundamental matrix describes the correspondence in more general and fundamental terms of projective geometry. This is captured mathematically by the relationship between a fundamental matrix F and its corresponding essential matrix E which is E=(K′)⊤FK K and K′ being the intrinsic calibration matrices of the two images involved.
Fundamental matrix (computer vision)	Introduction	The fundamental matrix is a relationship between any two images of the same scene that constrains where the projection of points from the scene can occur in both images. Given the projection of a scene point into one of the images the corresponding point in the other image is constrained to a line, helping the search, and allowing for the detection of wrong correspondences. The relation between corresponding points, which the fundamental matrix represents, is referred to as epipolar constraint, matching constraint, discrete matching constraint, or incidence relation.
Fundamental matrix (computer vision)	Projective reconstruction theorem	The fundamental matrix can be determined by a set of point correspondences. Additionally, these corresponding image points may be triangulated to world points with the help of camera matrices derived directly from this fundamental matrix. The scene composed of these world points is within a projective transformation of the true scene. Proof Say that the image point correspondence x↔x′ derives from the world point X under the camera matrices (P,P′) as x=PXx′=P′X Say we transform space by a general homography matrix H4×4 such that X0=HX The cameras then transform as P0=PH−1P0′=P′H−1 P0X0=PH−1HX=PX=x and likewise with P0′ still get us the same image points.
Fundamental matrix (computer vision)	Derivation of the fundamental matrix using coplanarity condition	The fundamental matrix can also be derived using the coplanarity condition.
Fundamental matrix (computer vision)	For satellite images	The fundamental matrix expresses the epipolar geometry in stereo images. The epipolar geometry in images taken with perspective cameras appears as straight lines. However, in satellite images, the image is formed during the sensor movement along its orbit (pushbroom sensor). Therefore, there are multiple projection centers for one image scene and the epipolar line is formed as an epipolar curve. However, in special conditions such as small image tiles, the satellite images could be rectified using the fundamental matrix.
Fundamental matrix (computer vision)	Properties	The fundamental matrix is of rank 2. Its kernel defines the epipole.
Fundamental matrix (computer vision)	Toolboxes	fundest is a GPL C/C++ library for robust, non-linear (based on the Levenberg–Marquardt algorithm) fundamental matrix estimation from matched point pairs and various objective functions (Manolis Lourakis). Structure and Motion Toolkit in MATLAB (Philip H. S. Torr) Fundamental Matrix Estimation Toolbox (Joaquim Salvi) The Epipolar Geometry Toolbox (EGT)
TNFRSF18	TNFRSF18	Tumor necrosis factor receptor superfamily member 18 (TNFRSF18), also known as glucocorticoid-induced TNFR-related protein (GITR) or CD357. GITR is encoded and tnfrsf18 gene at chromosome 4 in mice. GITR is type I transmembrane protein and is described in 4 different isoforms. GITR human orthologue, also called activation-inducible TNFR family receptor (AITR), is encoded by the TNFRSF18 gene at chromosome 1.
TNFRSF18	Function	GITR is a member of TNFR superfamily and shares high homology in cytoplasmic domain, characterized with cysteine pseudo-repeats, with other members of TNFRSF, such as CD137, OX40 or CD27. GITR is constitutively expressed on CD25+CD4+ regulatory T cells and its expression is upregulated on all T cell subsets after activation. GITR is also expressed on murine neutrophils and NK cells. GITR interacts with its ligand (GITRL) that is expressed on antigen-presenting cells (APC) and endothelial cells.
TNFRSF18	Function	AITR Human activation-inducible tumor necrosis factor receptor (AITR) and its ligand, AITRL, are important costimulatory molecules in the pathogenesis of autoimmune diseases. Despite the importance of these costimulatory molecules in autoimmune disease, their role in the autoimmune reaction to herniated disc fragments has yet to be explored.
TNFRSF18	Function	GITR GITR was identified as a new member of the TNF receptor superfamily, by comparing gene expression in untreated and DEX-treated murine T-cell lines. GITR is co-stimulatory surface receptor for T cells and after interaction with GITRL maintain T cell activation, proliferation, cytokine production, and rescue T cells from anti-CD3-induced apoptosis. GITR can be used as Treg marker and its signaling abrogates the suppressive function of regulatory T cells. Also, GITR plays role in Treg development, as it is expressed already at CD4+CD25+Foxp3- Treg progenitors. GITR-/- mice has no developmental problem and are fertile. They have complete block in anti-CD3-induced T cell activation and decrease in regulatory T cells progenitors. After infection challenge, GTIR-/- mice developed less inflammation than WT littermates.
TNFRSF18	GITR signaling	GITR does not have any enzymatic activity and signaling is propagated via recruiting TRAF-family members, specifically TRAF1, TRAF2 and TRAF5, to the GITR-signaling complex. The signaling is then mediated through NF-kB and MAPK pathways. There is an evidence that GITR has unique role for CD8+ and CD4+ T cells. GITR signaling lowers the threshold for CD28 signaling on CD8+ T cells or induces expression of CD137 on CD8+ memory T cells. For CD4+ regulatory T cells, GITR signaling promotes their expansion, inhibits Treg suppressive capacity and promotes resistance of effector T cells to Treg suppression.
TNFRSF18	GITR in disease	GITR is in high interest as one of the immune checkpoint molecules that have potential in cancer treatment. GITR signaling can promote antitumor and anti-infective immune response, but also can be a driver of autoimmune diseases. Different response to GITR signaling rely on the GITR expression on different immune cell types. How GITR signaling is modulated in the different cells remains unknown. GITR agonistic antibodies are in the clinical trials as activators of effector CD8 T cells, while decreasing number of circulating suppressive regulatory T cells. Limited response to GITR agonistic antibodies is enhanced in combination with anti-PD-1 or anti-CTLA-4 therapies. GITR-/- mice in pancreatitis model have reduced IkBα and decreased expression of NF-kB p65 protein in pancreatic tissue, and also increased pro-apoptotic markers (e.g. Bax) and decreased anti-apoptotic markers (e.g. Bcl-2). Asthma model: GITR activation drives an infiltration of eosinophils to the lungs and induces production of cytokines. Model of arthritis: GITR activation increase numbers of Th17 cells in secondary lymphoid organs and stimulate cytokine production. Model of atopic dermatitis: GITR-GITRL pathway activation supports the production of attractants of regulatory T cells (CCL17 and CCL27) and promotes production of Th2-induced cytokines. Inhibition of GITR-GITRL pathway potentially may decrease a severity of different diseases, as asthma, arthritis or atopic dermatitis.
TNFRSF18	GITR in disease	Atherosclerosis Atherosclerosis is autoinflammatory disease that belongs to the group of cardiovascular diseases (CVD). In atherosclerosis progression, plaques with modified low density lipoprotein (LDL) are formed. GITR expression was detected in plaques macrophages and T cells. Moreover, soluble GITR (sGITR) was present in patient's plasma. GITR potentially might be used as a biomarker of CVD patients, as its plaque expression and levels in plasma can distinguish the CVD patients from healthy controls.
Throw shade	Throw shade	The expressions "throw shade", "throwing shade", or simply "shade", are slang terms for a certain type of insult, often nonverbal. Journalist Anna Holmes called shade "the art of the sidelong insult". Merriam-Webster defines it as "subtle, sneering expression of contempt for or disgust with someone—sometimes verbal, and sometimes not".
Throw shade	History	The term can be found in Jane Austen's novel Mansfield Park (1814). Young Edmund Bertram is displeased with a dinner guest's disparagement of the uncle who took her in: "With such warm feelings and lively spirits it must be difficult to do justice to her affection for Mrs. Crawford, without throwing a shade on the Admiral."The slang version of "shade" originated from the black community. According to gender studies scholar John C. Hawley, the expression "throwing shade" was used in the 1980s by New York City's ethnic working-class in the "ballroom and vogue culture", particularly by gender nonconformists. He writes that it refers to "the processes of a publicly performed dissimulation that aims either to protect oneself from ridicule or to verbally or psychologically attack others in a haughty or derogatory manner."
Throw shade	Later use	The first major use of "shade" that introduced the slang to the greater public was in Jennie Livingston's documentary film, Paris Is Burning (1990), about the mid-1980s drag scene in Manhattan. In the documentary, one of the drag queens, Dorian Corey, explains that shade derives from "reading", the "real art form of insults". Shade is a developed form of reading: "Shade is, I don't tell you you're ugly. But I don't have to tell you, because you know you're ugly. And that's shade."Willi Ninja, who also appeared in Paris Is Burning, described "shade" in 1994 as a "nonverbal response to verbal or nonverbal abuse. Shade is about using certain mannerisms in battle. If you said something nasty to me, I would just turn on you, and give you a look like: 'Bitch please, you're not even worth my time, go on.' ... It's like watching Joan Collins going against Linda Evans on Dynasty. ... Or when George Bush ran against Bill Clinton, they were throwing shade. Who got the bigger shade? Bush did because Clinton won." A New York Times letter to the editor in 1993 criticized the newspaper for commenting on Bill Clinton's hair: "The Sunday Stylers are the last people I'd expect to throw shade on President Bill's hair pursuits."According to E. Patrick Johnson, to throw shade is to ignore someone: "If a shade thrower wishes to acknowledge the presence of the third party, he or she might roll his or her eyes and neck while poking out his or her lips. People throw shade if they do not like a particular person or if that person has dissed them in the past. ... In the playful mode, however, a person may throw shade at a person with whom he or she is a best friend." The expression was further popularized by the American reality television series RuPaul's Drag Race, which premiered in 2009. In 2015, Anna Holmes of The New York Times Magazine wrote: Shade can take many forms — a hard, deep look that could be either aggressive or searching, a compliment that could be interpreted as the opposite of one. E. Patrick Johnson, who teaches performance studies and African-American studies at Northwestern University, and who has written about the tradition of insults in the gay and black communities, explains: "If someone walks into a room with a hideous dress, but you don’t want to say it's hideous, you might say, 'Oooh … look at you!'" At its most refined, shade should have an element of plausible deniability, so that the shade-thrower can pretend that he or she didn't actually mean to behave with incivility, making it all the more delicious.
Lookalike audience	Lookalike audience	A lookalike audience is a group of social network members who are determined as sharing characteristics with another group of members. In digital advertising, it refers to a targeting tool for digital marketing, first initiated by Facebook, which helps to reach potential customers online who are likely to share similar interests and behaviors with existing customers. Since Facebook debuted this feature in 2013, additional advertising platforms have followed suit, including Google Ads, Outbrain, Taboola, LinkedIn Ads and others.
Lookalike audience	Considerations	Lookalike audiences anatomize existing customers and their user profiles to find the commonalities between the existing audience. This helps to find highly-qualified customers who previously would have been difficult to identify and reach. This expands the potential audience in different countries and applies to new differentiated audience segments; This approach saves time and lowers advertising costs for the acquisition of a new audience.
Lookalike audience	Considerations	In order to be effective, a lookalike audience seed needs to be homogeneous. This is commonly achieved using a consistent behavioral pattern. The homogeneity of the lookalike seed has a greater influence on the audience's effectiveness than the size of this sample group. In Facebook, the minimal lookalike seed size is 100 users from the same country. Facebook generally recommends creating a seed from an audience of 1,000 to 5,000 users.Lookalike audiences might have limited effects on small companies or startups because of the small sample size of their existing audience, which would inevitably lead to insufficient data drawn from the current audience and interference from outliers. Namely, there would be no high bounce rate with these companies' websites.
Lookalike audience	Examples of seeds	Marketers use many data sources to create lookalike seeds. Some examples of eCommerce lookalike seeds include: CRM-based – A seed based on an email or phone number list of customers who have had a past interaction with the business. This can be further segmented, for example customers with the highest lifetime value or past purchases of a specific product. Conversion-based – A seed based on users that have performed an action such as a Purchase or Lead form submission on the website. Engagement-based – A seed based on users segmented by their engagement, such as pages viewed, time spent on the site, video views, etc.
Lookalike audience	Methodology	Facebook, as an example, takes three steps to build a lookalike audience: Choose the audience seed to build a lookalike audience from. This can range from page fans, visitors to the website, and customer lists etc. Generally the base audience should be composed of a minimum of 500 people. Larger pools will increase the accuracy of the lookalike audience. Choose the specific location (country or region) to find a similar audience in.
Lookalike audience	Methodology	Customize the audience size. Facebook offers a range of percentiles from 1% to 10%, indicating the size of the combined population of the locations selected. Larger audiences provide a wider reach, but a smaller lookalike audience is more targeted, which means ads are seen by fewer people, but they are likely to be better aligned to the features of the audience's seed.
Lookalike audience	Debate	One study has shown that the tool of lookalike audiences, to some degrees, does well in generally advertising results. It is also listed as an important trend of pay-per-click (PPC) by Delhi School of Internet Marketing. However, debates over such a third party behavioral targeting being used for digital marketing hasn't stopped either, because using the data of customers is against online privacy settings.In 2019, limitations were put in place by Facebook to stop discriminatory targeting of audiences according to zip code, income levels and demographics (age and gender). In June 2022, the U.S. Justice Department Civil Rights Division filed a lawsuit in the Southern New York U.S. District Court against Meta Platforms alleging that the Lookalike audience tool for targeted advertising on Facebook discriminates against users based on their race, color, religion, sex, disability, familial status, and national origin in its distribution of housing advertisements in violation of Title VIII of the Civil Rights Act of 1968. Meta Platforms settled with the Justice Department on the same day the lawsuit was filed.
Spillage	Spillage	In industrial production, spillage is the loss of production output due to production of a series of defective or unacceptable products which must be rejected. Spillage is an often costly event which occurs in manufacturing when a process degradation or failure occurs that is not immediately detected and corrected, and in which defective or reject product therefore continues to be produced for some extended period of time.
Spillage	Spillage	Spillage results in costs due to lost production volume, excessive scrap, delayed delivery of product, and wastage of human and capital equipment resources. Minimization of the occurrence and duration of manufacturing spillage requires that closed-loop control and associated process monitoring and metrology functions be integrated into critical steps of the overall manufacturing process. The extent to which process control is complete and metrology is high resolution so as to be comprehensive determines the extent to which spillages will be prevented.
Angstrom exponent	Angstrom exponent	The Angstrom exponent or Ångström exponent is a parameter that describes how the optical thickness of an aerosol typically depends on the wavelength of the light.
Angstrom exponent	Definition	In 1929, the Swedish physicist Anders K. Ångström found that the optical thickness of an aerosol depends on the wavelength of light according to the power law τλτλ0=(λλ0)−α where τλ is the optical thickness at wavelength λ , and τλ0 is the optical thickness at the reference wavelength λ0 . The parameter α is the Angstrom exponent of the aerosol.
Angstrom exponent	Significance	The Angstrom exponent is inversely related to the average size of the particles in the aerosol: the smaller the particles, the larger the exponent. For example, cloud droplets are usually large, and thus clouds have very small Angstrom exponent (nearly zero), and the optical depth does not change with wavelength. That is why clouds appear to be white or grey. This relation can be used to estimate the particle size of an aerosol by measuring its optical depth at different wavelengths.
Angstrom exponent	Determining the exponent	In principle, if the optical thickness at one wavelength and the Angstrom exponent are known, the optical thickness can be computed at a different wavelength. In practice, measurements are made of the optical thickness of an aerosol layer at two different wavelengths, and the Angstrom exponent is estimated from these measurements using this formula. The aerosol optical thickness can then be derived at all other wavelengths, within the range of validity of this formula.
Angstrom exponent	Determining the exponent	For measurements of optical thickness τλ1 and τλ2 taken at two different wavelengths λ1 and λ2 respectively, the Angstrom exponent is given by log log ⁡λ1λ2 The Angstrom exponent is now routinely estimated by analyzing radiation measurements acquired on Earth Observation platforms, such as AErosol RObotic NETwork, or AERONET.
Fingers (game)	Fingers (game)	Fingers or finger spoof is a drinking game where players guess the number of participating players who will keep their finger on a cup at the end of a countdown. A correct guess eliminates the player from the game and ensures they will not have to drink the cup. The last person in the game loses and must consume the cup contents. The cup could be a pint glass, pitcher, or other vessel (large enough for all players to put one finger on the rim) that is filled with a sip or small sample of all players' own beverage prior to the start of the game.
Fingers (game)	Rules and setup	Equipment Alcoholic beverages, typically wine, beer or mixed spirits A pint glass, pitcher, or other vessel, but ideally a bowl.
Fingers (game)	Rules and setup	Setup and common rules Fingers starts by a participant offering his empty or almost-empty pint glass, pitcher, or other vessel to be used as "the cup." Popular in circles where the game us called "Scoff", the game starts with someone yelling "Scoff!" followed by players assembling around the cup. Each player pours a small amount of their own beverage into "the cup".
Fingers (game)	Rules and setup	The game progresses in a series of turns with the first turn going to the game participant who suggested playing the game. Each turn starts with all players putting one finger on the rim of the cup. When all fingers are on the rim, the player whose turn it is announces, "three - two - one" followed by a number. The number is the player's guess at how many fingers will remain on the cup. All participating players, including the player whose turn it is, have the option to keep their finger on the cup or to remove it from the cup after the "three - two - one" count. A correct guess eliminates the player from the game (a win), an incorrect guess keeps the player active in the game.
Fingers (game)	Rules and setup	The game progresses clockwise as each player takes their turn. The game ends when only one person remains- the loser. The loser must drink the contents of the cup. If the game is played again, a second round, the loser is the first to start the game. Variations and other rules Two-man Fingers: a version of fingers played with only 2 players. Each player uses both index fingers (4 fingers total) to start the game. Fingers are ordered player - opponent - player - opponent. The game progresses as if 4 individuals were playing.
Fingers (game)	Rules and setup	Balk: a balk is when the a player whose turn it is starts the "three - two - one" count and does not announce, or waits too long to announce their guess number. The player loses his / her turn if a balk occurs. There should be no gap in timing when announcing the guess number after the "three - two - one" series.
Fingers (game)	Rules and setup	Slow Pull: a slow pull is when a participant is slow or decides late to remove their finger from the cup (within a second). Most players will agree that counting the remaining fingers after a number is called and then deciding to remove his / her finger (within a second) to cheat the current active player is next to impossible. For this reason, slow pulls should be considered fair game unless it is unreasonably delayed or there are fewer than 3-4 players remaining. All players (eliminated players included) should make the judgement call.
Fingers (game)	Rules and setup	Social: a social is when all players take one sip of their own drink. Socials occur when everyone coincidentally removes their finger during a call. Non-Celebration for the truly advanced: If you guess correctly and eliminate yourself from the game you can not show any emotion that might offend the other participants (celebrating, fist-pumping, smiling, etc.). If you do, you must apologize to the remaining players for your unwarranted celebration and re-enter the game. Idiot Cup: when one player calls out a number but makes the result impossible by their own action (i.e., calling 0 and leaving their own finger on the cup or calling 5 with only 4 players left like an idiot). In this case, the player has to finish the drink. Penalty: where a player calls a number out of turn they must down the drink. Finger Spoof Variations: Traditionally played in the pubs and sports clubs of Gloucestershire as an alternative to full (Three-Coin) spoof. The game is played for any pre-agreed forfeit including purchasing a round of drinks, drinking an unpleasant drink as above, snorting snuff/mustard, etc. Penalties should also be pre-agreed. Zero is referred to as Spoof. No countdown occurs. Players should be alert. False/impossible shout results in a penalty.
Advanced Distributed Learning	Advanced Distributed Learning	The Advanced Distributed Learning (ADL) Initiative is a US government program that conducts research and development on distributed learning and coordinates related efforts broadly across public and private organizations. ADL reports to the Defense Human Resources Activity (DHRA), under the Director, DHRA. Although it is a DoD program, ADL serves the entire US federal government, operates a global partnership network including international defense ministries and US-based academic partners, and collaborates closely with industry and academia. ADL advises the DoD and US government on emerging learning technologies, best practices for improving learning effectiveness and efficiency, and methods for enhancing interoperability. Notable ADL contributions to distributed learning include the Sharable Content Object Reference Model (SCORM), Experience API (xAPI), and the DoD Instruction 1322.26.
Advanced Distributed Learning	History	The ADL Initiative traces its antecedents to the early 1990s, when Congress authorized and appropriated funds for the National Guard to build prototype electronic classrooms and learning networks to increase personnel's access to learning opportunities. By the mid-1990s, DoD realized the need for a more coordinated approach, and the 1996 Quadrennial Defense Review formalized this by directing development of a department-wide strategy for modernizing technology-based education and training. This strategy became the original ADL Initiative, and in 1998, the Deputy Secretary of Defense directed the Under Secretary of Defense for Personnel and Readiness (USD(P&R), in collaboration with the Services, Joint Staff, Under Secretaries of Defense for Acquisition and Technology and the Comptroller), to lead ADL. The Deputy Secretary of Defense also directed the USD(P&R) to produce the department-wide policy for advanced distributed learning, develop a corresponding “master plan” to carry out the policy, and to ensure sufficient programs and resources were available for the associated implementation (see the 1999 ADL Strategic Plan in Appendix 1 for more details).By 1998, the DoD and other Federal agencies (e.g., the Department of Labor) had each established their own ADL projects, and the Office of Science and Technology Policy (OSTP) moved to consolidate these via the Federal Training Technology Initiative. Thus, following guidance from Congress, OSTP, and the National Partnership for Reinventing Government, the DoD ADL Initiative was grown into a Federal-wide program. Specific direction for this can be found in Section 378 of Public Law 105-261, the Strom Thurmond National Defense Authorization Act for Fiscal Year 1999, which required the Secretary of Defense to develop a strategic plan for expanding distance learning initiatives, as well as Executive Order 13111 (President William J. Clinton, 12 January 1999). The Executive Order, titled “Using Technology to Improve Training Opportunities for Federal Government Employees,” established a task force and advisory committee to explore how federal training programs, initiatives, and policies can better support lifelong learning through the use of learning technologies and to provide learning standards, specifications, and applications which can be sustained and extended to incorporate new technologies and learning science as they occur.
Advanced Distributed Learning	History	Shortly after President Clinton signed Executive Order 13111, the Pentagon released the Department of Defense Strategic Plan for Advanced Distributed Learning (April 30, 1999) and the corresponding Department of Defense Implementation Plan for Advanced Distributed Learning (May 19, 2000). This strategy empowers the ADL Initiative to: Influence the development/use of common industry standards Enable acquisition of interoperable tools and content Create a robust and dynamic network infrastructure for distribution Enable the modernization of supporting resources Engender cultural change to move from “classroom-centric” to “learner-centric”Since its inception in the 1990s, the ADL Initiative has achieved several notable milestones, including the development of SCORM, ADL PlugFests, xAPI, and the Total Learning Architecture. More information about the history and products of ADL can be found in the ADL-sponsored book, Learning on Demand: ADL and the Future of e-Learning, published in 2010.
Advanced Distributed Learning	Organization	The ADL Initiative reports to the Defense Human Resources Activity (DHRA), under the Director, DHRA. Originally, the ADL Initiative reported to the OSD Director for Readiness and Training Policy and Programs in the Under Secretary of Defense for Personnel and Readiness (USD(P&R)) chain of command. Until April 18, 2021, the ADL Initiative reported to the Deputy Assistant Secretary of Defense for Force Education and Training (DASD(FE&T)), who reported to the Assistant Secretary of Defense for Readiness (ASD(R)), who in turn reported to the Under Secretary for Personnel and Readiness (USD(P&R)) within the Office of the Secretary of Defense.
Advanced Distributed Learning	Subject Areas	ADL uses the term “distributed learning” broadly, to refer to all network-centric learning technologies and their corresponding best practices for their use. Similarly, ADL uses the term “learning” to include education, training, operational performance support, and other forms of ad hoc, just-in-time, or self-directed learning. Within these topical areas, ADL conducts research and development (Budget Area 6.3, Advanced Technology Development), facilitates coordination, and assists with the implementation of emerging science and technologies. More precisely, ADL's work emphasizes the following six areas: [7] e-Learning (e.g., traditional web-based courseware) Mobile learning (m-Learning) and associated mobile performance support Web-based virtual worlds and simulations Learning analytics and performance modeling Associated learning theory (e.g., pedagogy, andragogy, instructional design) Distributed learning interoperability specifications
Advanced Distributed Learning	SCORM	When ADL was established, the use of Learning Management Systems (LMSs) was increasing rapidly, but the content delivered through those systems remained separated (locked into silos). For example, while the Navy and Army have standard courses with similar content, that content could not be shared and reused from one service to another because their LMSs would not allow it. The silo’d nature of content delivered through LMSs was not cost efficient, and became one of ADL's first challenges to tackle resulting in the development of the SCORM (sharable content object reference model).SCORM, which integrates a set of related technical standards, specifications, and guidelines designed to meet high-level requirements—accessible, reusable, interoperable, and durable content and systems is arguably one of ADL's most well known projects. SCORM content can be delivered to learners via any SCORM-conformant LMS using the same version of SCORM. Due to the Department of Defense Instruction (DoDI) 1322.26, SCORM is a mature technology which has been widely adopted.
Advanced Distributed Learning	Experience API	In 2011, ADL recognized the need for a software specification that tracks learning experiences that occur outside of a LMS and a web browser. As a result, ADL issued a Broad Agency Announcement (BAA) asking for assistance in improving SCORM. The BAA was awarded to Rustici Software, a Nashville-based software company experienced with SCORM.
Advanced Distributed Learning	Experience API	Rustici Software conducted numerous interviews with the e-learning community to determine where improvements needed to be made and developed the research version of the Experience API specification as a result. This process was called Project Tin Can. The moniker “Tin Can API” was derived from Project Tin Can. When version 1.0 was officially released in April 2013, the specification was dubbed “xAPI” but by that time, some people already knew the specification by the original moniker. The Experience API (xAPI) allows the capture of big data on human performance, along with associated instructional content or performance context information. xAPI applies “activity streams” to tracking data and provides sub-APIs to access and store information about state and content. This enables nearly dynamic tracking of activities from any platform or software system—from traditional LMSs to mobile devices, simulations, wearables, physical beacons, and more.
Advanced Distributed Learning	Department of Defense Instruction 1322.26	Under delegated authority, ADL stewards DoDI 1322.26, “Development, Management, and Delivery of Distributed Learning.” This DoDI provides guidance to support implementation of DoD Directive (DoDD) 1322.18, “Military Training.”
Chiraphos	Chiraphos	Chiraphos is a chiral diphosphine employed as a ligand in organometallic chemistry. This bidentate ligand chelates metals via the two phosphine groups. Its name is derived from its description — being both chiral and a phosphine. As a C2-symmetric ligand, chiraphos is available in two enantiomeric forms, S,S and R,R, each with C2 symmetry.
Chiraphos	Preparation	Chiraphos is prepared from S,S or R,R-2,3-butanediol, which are derived from commercially available S,S or R,R-tartaric acid; the technique of using cheaply available enantiopure starting materials is known as chiral pool synthesis. The diol is tosylated and then the ditosylate is treated with lithium diphenylphosphide. The ligand was an important demonstration of how the conformation of the chelate ring can affect asymmetric induction by a metal catalyst. Prior to this work, in most chiral phosphines, e.g., DIPAMP, phosphorus was the stereogenic center.
GALNT13	GALNT13	Polypeptide N-acetylgalactosaminyltransferase 13 is an enzyme that in humans is encoded by the GALNT13 gene.The GALNT13 protein is a member of the UDP-N-acetyl-alpha-D-galactosamine:polypeptide N-acetylgalactosaminyltransferase (GalNAcT; EC 2.4.1.41) family, which initiate O-linked glycosylation of mucins (see MUC3A, MIM 158371) by the initial transfer of N-acetylgalactosamine (GalNAc) with an alpha-linkage to a serine or threonine residue.[supplied by OMIM]
Junior showmanship	Junior showmanship	Junior showmanship (also called junior handling) is a sport for young people (called "Juniors") in which they exhibit their dog handling skills in an event similar to a conformation dog show. Unlike a conformation show, it is the young handlers who are judged, not their dogs.
Junior showmanship	History	County agricultural fairs in the United States began holding livestock judging contests for members of the 4-H, a club run by state agricultural extensions for children of farm families, in the early 1900s. Showmanship, in which the child was judged for ability to display "an animal to its greatest advantage" was a component of livestock judging. As the idea of 4-H as a youth development club, not just a club for future agriculturalists, spread around the world, horses and pet animals were added to showmanship categories.The first dog handling competition for children at a formal dog show was held in 1932 at the Westbury Kennel Club Show in Long Island, New York, in the United States. In 1933 the Westminster Kennel Club in New York offered a children's handling class, and prizes were established in the names of early promoters of children's events, Leonard Brumby, Sr, and George F. Foley. The American Kennel Club recognized Junior Showmanship as a dog show class in 1971.Today, major Junior Showmanship competition is offered worldwide through Fédération Cynologique Internationale clubs, as well as through the Kennel Club (UK), The Canadian Kennel Club, The American Kennel Club, The United Kennel Club (US), as well as 4-H and similar clubs. Other show-giving dog clubs and businesses may also offer Junior Showmanship events.
Junior showmanship	Purpose	Learning sportsmanship and developing knowledge of the dog are given as the purpose for Junior Showmanship (Junior Handling) by most organizations. The Junior learns sportsmanship, ring procedures, and grooming and showing techniques specific to the dog he or she is showing, and develops a close bond with the dog. For the major show-giving bodies, Junior Showmanship can also be an apprenticeship in dog handling, preparing young people for careers in dog handling, raising, and training.
Junior showmanship	Eligibility	In general, children and young people may compete with dogs of any breed or in some cases, mixed breed dogs. Competition is by age group, in various classification levels. Rules are specific to each show giving organization.
Junior showmanship	Eligibility	Children as young as two years old are allowed in the ring by the United Kennel Club (US), at age four by the Canadian Kennel Club, at age six by the Kennel Club (UK), and at age nine by the American Kennel Club and the 4-H. All end eligibility at age eighteen except for the Kennel Club (UK), which allows Juniors to compete until they are 24. Fédération Cynologique Internationale clubs have similar rules.
Junior showmanship	Nature of the competition	The Junior Showmanship competition is organized in a similar manner to a conformation dog show. The Juniors are separated into their age and experience levels, and enter the ring in order of the size of their dog. The juniors must move their dogs around the ring according to the instructions of the judge in pre determined patterns. The judge notes whether or not the Junior follows instructions correctly and presents the dog properly according to the dog's breed or type. Dogs are examined as in a conformation show, but the emphasis is on how the Junior interacts with the dog and the judge, not on the quality of the dog.
Junior showmanship	Nature of the competition	At the basic or novice level, children are judged on how well they follow the judge's instructions, their understanding of ring procedure and of the standard of the breed or type of dog they are showing. In some clubs, the children may be quizzed or questioned by the judge. In close competition between advanced Juniors, judging is also based on the Junior's knowledge of his or her dog's faults, and how well they disguise the faults through skillful handling so that "what a judge observes are animals at the top of their form."
Junior showmanship	Related activities	Junior Showmanship is a sport limited to children and young people, but many young handlers also enter adult show classes in conformation and performance (obedience, agility, hunting events, flyball, etc.) as well. Some organizations have set up separate performance event categories for junior handlers.
Junior showmanship	Judging	As junior handling is a separate sport from regular conformation showing, judges are usually given separate training and are expected to know the rules for the sport. Westminster continues to be the "crown jewel" of the Juniors Competition. Only one winner of Best Junior Handler at this prestigious show has ever returned to judge the event.
Diamond Quadrilateral	Diamond Quadrilateral	The Diamond Quadrilateral is a project of the Indian Railways to establish a high-speed rail network in India. The Diamond Quadrilateral will connect the four mega cities of India, viz. Delhi, Mumbai, Kolkata and Chennai, similar to the Golden Quadrilateral highway system. High-speed train on Mumbai-Ahmedabad section will be the first high-speed train corridor to be implemented in the country. On 9 June 2014, the President of India Pranab Mukherjee, officially mentioned that the Government led by Prime Minister Narendra Modi will launch a Diamond Quadrilateral project of high-speed trains.
Diamond Quadrilateral	History	Prior to the 2014 general election, the two major national parties (Bharatiya Janata Party and Indian National Congress) pledged to introduce high-speed rail. The INC pledged to connect all of India's million-plus cities by high-speed rail, whereas BJP, which won the election, promised to build the "Diamond Quadrilateral" project, which would connect the cities of Chennai, Delhi, Kolkata, and Mumbai via high-speed rail. This project was approved as a priority for the new government in the incoming president's speech. Construction of one kilometer of high speed railway track will cost ₹100 crore (US$13 million) – ₹140 crore (US$18 million) which is 10-14 times higher than the cost of construction of standard railway.India's Union Council of Ministers passed the proposal of Japan to build India's first high-speed railway on 10 December 2015. The planned rail will run approximately 500 km (310 mi) between Mumbai and the western city of Ahmedabad at a top speed of 320 km/h (200 mph). Under this proposal, the construction began in 2017 and is expected to be completed in the year 2022. The estimated cost of this project is ₹980 billion (US$12 billion) and is financed by a low-interest loan from Japan. Operation is officially targeted to begin in 2023, but India has announced intentions to attempt to bring the line into operation one year earlier. It will transport the passengers from Ahmedabad to Mumbai in just 3 hours and its ticket fare will be cheaper than air planes, that is, ₹2,500-₹3,000.
Diamond Quadrilateral	Current status	As of July 2020, NHSRCL has floated almost 60% of tenders for civil works, and almost 60% of land is acquired for the first Mumbai-Ahmadabad corridor and the deadline of the project is December 2023.
Diamond Quadrilateral	Current status	The National High Speed Rail Corporation Limited, the implementing body of the project, has planned 7 routes which are Delhi to Varanasi via Noida, Agra and Lucknow; Varanasi to Howrah via Patna; Delhi to Ahmadabad via Jaipur and Udaipur; Delhi to Amritsar via Chandigarh, Ludhiana and Jalandhar; Mumbai to Nagpur via Nasik; Mumbai to Hyderabad via Pune and Chennai to Mysore via Bangalore.
Diamond Quadrilateral	Current status	According to reports, the NHAI will soon acquire land to lay tracks for high-speed trains along greenfield expressways for integrated development of the rail transport network in the country. to expedite the project, the Indian Railways along with the National Highways Authority of India (NHAI) will begin the process of acquiring additional land. The decision to acquire additional land was taken during a recent meeting of a group of infrastructure ministers led by Union Minister Nitin Gadkari. During the infra sector group meeting, it was decided that the NHAI will take over land acquisition and a 4-member committee was constituted to take this process forward. The four-member task force will work out the modalities for acquiring land and sharing the cost. It may be noted that the Indian Railways is in the process of preparing the blueprint of 7 high-speed rail routes in the country. As per reports, The railway board has also written to the NHAI and given details of seven high-speed rail corridors for running bullet trains for which the detailed project reports are being prepared. NHAI has been asked to depute a nodal officer for this purpose for better integration of the mammoth planning exercise. Railways plans to run bullet trains on 7 important new routes of the country.
Demand priority	Demand priority	Demand priority is a media-access method used in 100BaseVG, a 100 megabit per second (Mbit/s) Ethernet implementation proposed by Hewlett-Packard (HP) and AT&T Microelectronics, later standardized as IEEE 802.12. Demand priority shifts network access control from the workstation to a hub. This access method works with a star topology. In this method, a node that wishes to transmit indicates this wish to the hub and also requests high- or regular-priority service for its transmission. After it obtains permission, the node begins transmitting to the hub. The hub is responsible for passing the transmission on to the destination node; that is, the hub is responsible for providing access to the network. A hub will pass high priority transmissions through immediately, and will pass regular-priority transmissions through as the opportunity arises. By letting the hub manage access, the architecture is able to guarantee required bandwidths and requested service priority to particular applications or nodes. It also can guarantee that the network can be scaled up (enlarged) without loss of bandwidth.
Demand priority	Demand priority	Demand priority helps increase bandwidth in the following ways: A node does not need to keep checking whether the network is idle before transmitting. In current Ethernet implementations, a wire pair is dedicated to this task. By making network checking unnecessary, demand priority frees a wire pair. This is fortunate, because the 100BaseVG specifications use quartet signalling, which needs four available wire pairs. Heavy traffic can effectively bring standard Ethernet networks to a standstill, because nodes spend most of their time trying to access the network.
Demand priority	Demand priority	With demand priority, the hub needs to pass a transmission on only to its destination, so that overall network traffic is decreased. This means there is more bandwidth available for heavy network traffic.
Retraction (topology)	Retraction (topology)	In topology, a branch of mathematics, a retraction is a continuous mapping from a topological space into a subspace that preserves the position of all points in that subspace. The subspace is then called a retract of the original space. A deformation retraction is a mapping that captures the idea of continuously shrinking a space into a subspace. An absolute neighborhood retract (ANR) is a particularly well-behaved type of topological space. For example, every topological manifold is an ANR. Every ANR has the homotopy type of a very simple topological space, a CW complex.
Retraction (topology)	Definitions	Retract Let X be a topological space and A a subspace of X. Then a continuous map r:X→A is a retraction if the restriction of r to A is the identity map on A; that is, {\textstyle r(a)=a} for all a in A. Equivalently, denoting by ι:A↪X the inclusion, a retraction is a continuous map r such that id A, that is, the composition of r with the inclusion is the identity of A. Note that, by definition, a retraction maps X onto A. A subspace A is called a retract of X if such a retraction exists. For instance, any non-empty space retracts to a point in the obvious way (the constant map yields a retraction). If X is Hausdorff, then A must be a closed subset of X.
Retraction (topology)	Definitions	If {\textstyle r:X\to A} is a retraction, then the composition ι∘r is an idempotent continuous map from X to X. Conversely, given any idempotent continuous map {\textstyle s:X\to X,} we obtain a retraction onto the image of s by restricting the codomain. Deformation retract and strong deformation retract A continuous map F:X×[0,1]→X is a deformation retraction of a space X onto a subspace A if, for every x in X and a in A, and F(a,1)=a. In other words, a deformation retraction is a homotopy between a retraction and the identity map on X. The subspace A is called a deformation retract of X. A deformation retraction is a special case of a homotopy equivalence. A retract need not be a deformation retract. For instance, having a single point as a deformation retract of a space X would imply that X is path connected (and in fact that X is contractible). Note: An equivalent definition of deformation retraction is the following. A continuous map {\textstyle r:X\to A} is a deformation retraction if it is a retraction and its composition with the inclusion is homotopic to the identity map on X. In this formulation, a deformation retraction carries with it a homotopy between the identity map on X and itself.
Retraction (topology)	Definitions	If, in the definition of a deformation retraction, we add the requirement that F(a,t)=a for all t in [0, 1] and a in A, then F is called a strong deformation retraction. In other words, a strong deformation retraction leaves points in A fixed throughout the homotopy. (Some authors, such as Hatcher, take this as the definition of deformation retraction.) As an example, the n-sphere {\textstyle S^{n}} is a strong deformation retract of {\textstyle \mathbb {R} ^{n+1}\backslash \{0\};} as strong deformation retraction one can choose the map F(x,t)=((1−t)+t‖x‖)x.
Retraction (topology)	Definitions	Cofibration and neighborhood deformation retract A map f: A → X of topological spaces is a (Hurewicz) cofibration if it has the homotopy extension property for maps to any space. This is one of the central concepts of homotopy theory. A cofibration f is always injective, in fact a homeomorphism to its image. If X is Hausdorff (or a compactly generated weak Hausdorff space), then the image of a cofibration f is closed in X.
Retraction (topology)	Definitions	Among all closed inclusions, cofibrations can be characterized as follows. The inclusion of a closed subspace A in a space X is a cofibration if and only if A is a neighborhood deformation retract of X, meaning that there is a continuous map u:X→[0,1] with {\textstyle A=u^{-1}\!\left(0\right)} and a homotopy {\textstyle H:X\times [0,1]\rightarrow X} such that {\textstyle H(x,0)=x} for all x∈X, H(a,t)=a for all a∈A and t∈[0,1], and {\textstyle H\left(x,1\right)\in A} if u(x)<1 .For example, the inclusion of a subcomplex in a CW complex is a cofibration.
Retraction (topology)	Properties	One basic property of a retract A of X (with retraction r : X → A {\textstyle r:X\to A} ) is that every continuous map f : A → Y {\textstyle f:A\rightarrow Y} has at least one extension g : X → Y , {\textstyle g:X\rightarrow Y,} namely g = f ∘ r {\textstyle g=f\circ r} . Deformation retraction is a particular case of homotopy equivalence. In fact, two spaces are homotopy equivalent if and only if they are both homeomorphic to deformation retracts of a single larger space. Any topological space that deformation retracts to a point is contractible and vice versa. However, there exist contractible spaces that do not strongly deformation retract to a point.
Retraction (topology)	No-retraction theorem	The boundary of the n-dimensional ball, that is, the (n−1)-sphere, is not a retract of the ball. (See Brouwer fixed-point theorem § A proof using homology or cohomology.)
Retraction (topology)	Absolute neighborhood retract (ANR)	A closed subset {\textstyle X} of a topological space {\textstyle Y} is called a neighborhood retract of {\textstyle Y} if {\textstyle X} is a retract of some open subset of {\textstyle Y} that contains {\textstyle X} Let C be a class of topological spaces, closed under homeomorphisms and passage to closed subsets. Following Borsuk (starting in 1931), a space {\textstyle X} is called an absolute retract for the class C , written AR {\textstyle \operatorname {AR} \left({\mathcal {C}}\right),} if {\textstyle X} is in C and whenever {\textstyle X} is a closed subset of a space {\textstyle Y} in C , {\textstyle X} is a retract of {\textstyle Y} . A space {\textstyle X} is an absolute neighborhood retract for the class C , written ANR {\textstyle \operatorname {ANR} \left({\mathcal {C}}\right),} if {\textstyle X} is in C and whenever {\textstyle X} is a closed subset of a space {\textstyle Y} in C , {\textstyle X} is a neighborhood retract of {\textstyle Y} Various classes C such as normal spaces have been considered in this definition, but the class M of metrizable spaces has been found to give the most satisfactory theory. For that reason, the notations AR and ANR by themselves are used in this article to mean AR ⁡(M) and ANR ⁡(M) .A metrizable space is an AR if and only if it is contractible and an ANR. By Dugundji, every locally convex metrizable topological vector space {\textstyle V} is an AR; more generally, every nonempty convex subset of such a vector space {\textstyle V} is an AR. For example, any normed vector space (complete or not) is an AR. More concretely, Euclidean space {\textstyle \mathbb {R} ^{n},} the unit cube {\textstyle I^{n},} and the Hilbert cube {\textstyle I^{\omega }} are ARs.
Retraction (topology)	Absolute neighborhood retract (ANR)	ANRs form a remarkable class of "well-behaved" topological spaces. Among their properties are: Every open subset of an ANR is an ANR.
Retraction (topology)	Absolute neighborhood retract (ANR)	By Hanner, a metrizable space that has an open cover by ANRs is an ANR. (That is, being an ANR is a local property for metrizable spaces.) It follows that every topological manifold is an ANR. For example, the sphere {\textstyle S^{n}} is an ANR but not an AR (because it is not contractible). In infinite dimensions, Hanner's theorem implies that every Hilbert cube manifold as well as the (rather different, for example not locally compact) Hilbert manifolds and Banach manifolds are ANRs.
Retraction (topology)	Absolute neighborhood retract (ANR)	Every locally finite CW complex is an ANR. An arbitrary CW complex need not be metrizable, but every CW complex has the homotopy type of an ANR (which is metrizable, by definition).
Retraction (topology)	Absolute neighborhood retract (ANR)	Every ANR X is locally contractible in the sense that for every open neighborhood {\textstyle U} of a point {\textstyle x} in {\textstyle X} , there is an open neighborhood {\textstyle V} of {\textstyle x} contained in {\textstyle U} such that the inclusion {\textstyle V\hookrightarrow U} is homotopic to a constant map. A finite-dimensional metrizable space is an ANR if and only if it is locally contractible in this sense. For example, the Cantor set is a compact subset of the real line that is not an ANR, since it is not even locally connected.
Retraction (topology)	Absolute neighborhood retract (ANR)	Counterexamples: Borsuk found a compact subset of {\textstyle \mathbb {R} ^{3}} that is an ANR but not strictly locally contractible. (A space is strictly locally contractible if every open neighborhood {\textstyle U} of each point {\textstyle x} contains a contractible open neighborhood of {\textstyle x} .) Borsuk also found a compact subset of the Hilbert cube that is locally contractible (as defined above) but not an ANR.
Retraction (topology)	Absolute neighborhood retract (ANR)	Every ANR has the homotopy type of a CW complex, by Whitehead and Milnor. Moreover, a locally compact ANR has the homotopy type of a locally finite CW complex; and, by West, a compact ANR has the homotopy type of a finite CW complex. In this sense, ANRs avoid all the homotopy-theoretic pathologies of arbitrary topological spaces. For example, the Whitehead theorem holds for ANRs: a map of ANRs that induces an isomorphism on homotopy groups (for all choices of base point) is a homotopy equivalence. Since ANRs include topological manifolds, Hilbert cube manifolds, Banach manifolds, and so on, these results apply to a large class of spaces.
Retraction (topology)	Absolute neighborhood retract (ANR)	Many mapping spaces are ANRs. In particular, let Y be an ANR with a closed subspace A that is an ANR, and let X be any compact metrizable space with a closed subspace B. Then the space {\textstyle \left(Y,A\right)^{\left(X,B\right)}} of maps of pairs {\textstyle \left(X,B\right)\rightarrow \left(Y,A\right)} (with the compact-open topology on the mapping space) is an ANR. It follows, for example, that the loop space of any CW complex has the homotopy type of a CW complex.
Retraction (topology)	Absolute neighborhood retract (ANR)	By Cauty, a metrizable space {\textstyle X} is an ANR if and only if every open subset of {\textstyle X} has the homotopy type of a CW complex.
Retraction (topology)	Absolute neighborhood retract (ANR)	By Cauty, there is a metric linear space {\textstyle V} (meaning a topological vector space with a translation-invariant metric) that is not an AR. One can take {\textstyle V} to be separable and an F-space (that is, a complete metric linear space). (By Dugundji's theorem above, {\textstyle V} cannot be locally convex.) Since {\textstyle V} is contractible and not an AR, it is also not an ANR. By Cauty's theorem above, {\textstyle V} has an open subset {\textstyle U} that is not homotopy equivalent to a CW complex. Thus there is a metrizable space {\textstyle U} that is strictly locally contractible but is not homotopy equivalent to a CW complex. It is not known whether a compact (or locally compact) metrizable space that is strictly locally contractible must be an ANR.
Collagen, type VIII, alpha 1	Collagen, type VIII, alpha 1	Collagen alpha-1(VIII) chain is a protein that in humans is encoded by the COL8A1 gene.This gene encodes one of the two alpha chains of type VIII collagen. The gene product is a short chain collagen and a major component of the basement membrane of the corneal endothelium. The type VIII collagen fibril can be either a homo- or a heterotrimer. Alternatively spliced transcript variants encoding the same isoform have been observed.
Dendrimer	Dendrimer	Dendrimers are highly ordered, branched polymeric molecules. Synonymous terms for dendrimer include arborols and cascade molecules. Typically, dendrimers are symmetric about the core, and often adopt a spherical three-dimensional morphology. The word dendron is also encountered frequently. A dendron usually contains a single chemically addressable group called the focal point or core. The difference between dendrons and dendrimers is illustrated in the top figure, but the terms are typically encountered interchangeably.
Dendrimer	Dendrimer	The first dendrimers were made by divergent synthesis approaches by Fritz Vögtle in 1978, R.G. Denkewalter at Allied Corporation in 1981, Donald Tomalia at Dow Chemical in 1983 and in 1985, and by George R. Newkome in 1985. In 1990 a convergent synthetic approach was introduced by Craig Hawker and Jean Fréchet. Dendrimer popularity then greatly increased, resulting in more than 5,000 scientific papers and patents by the year 2005.
Dendrimer	Properties	Dendritic molecules are characterized by structural perfection. Dendrimers and dendrons are monodisperse and usually highly symmetric, spherical compounds. The field of dendritic molecules can be roughly divided into low-molecular weight and high-molecular weight species. The first category includes dendrimers and dendrons, and the latter includes dendronized polymers, hyperbranched polymers, and the polymer brush.
Dendrimer	Properties	The properties of dendrimers are dominated by the functional groups on the molecular surface, however, there are examples of dendrimers with internal functionality. Dendritic encapsulation of functional molecules allows for the isolation of the active site, a structure that mimics that of active sites in biomaterials. Also, it is possible to make dendrimers water-soluble, unlike most polymers, by functionalizing their outer shell with charged species or other hydrophilic groups. Other controllable properties of dendrimers include toxicity, crystallinity, tecto-dendrimer formation, and chirality.Dendrimers are also classified by generation, which refers to the number of repeated branching cycles that are performed during its synthesis. For example, if a dendrimer is made by convergent synthesis (see below), and the branching reactions are performed onto the core molecule three times, the resulting dendrimer is considered a third generation dendrimer. Each successive generation results in a dendrimer roughly twice the molecular weight of the previous generation. Higher generation dendrimers also have more exposed functional groups on the surface, which can later be used to customize the dendrimer for a given application.
Dendrimer	Synthesis	One of the first dendrimers, the Newkome dendrimer, was synthesized in 1985. This macromolecule is also commonly known by the name arborol. The figure outlines the mechanism of the first two generations of arborol through a divergent route (discussed below). The synthesis is started by nucleophilic substitution of 1-bromopentane by triethyl sodiomethanetricarboxylate in dimethylformamide and benzene. The ester groups were then reduced by lithium aluminium hydride to a triol in a deprotection step. Activation of the chain ends was achieved by converting the alcohol groups to tosylate groups with tosyl chloride and pyridine. The tosyl group then served as leaving groups in another reaction with the tricarboxylate, forming generation two. Further repetition of the two steps leads to higher generations of arborol.Poly(amidoamine), or PAMAM, is perhaps the most well known dendrimer. The core of PAMAM is a diamine (commonly ethylenediamine), which is reacted with methyl acrylate, and then another ethylenediamine to make the generation-0 (G-0) PAMAM. Successive reactions create higher generations, which tend to have different properties. Lower generations can be thought of as flexible molecules with no appreciable inner regions, while medium-sized (G-3 or G-4) do have internal space that is essentially separated from the outer shell of the dendrimer. Very large (G-7 and greater) dendrimers can be thought of more like solid particles with very dense surfaces due to the structure of their outer shell. The functional group on the surface of PAMAM dendrimers is ideal for click chemistry, which gives rise to many potential applications.Dendrimers can be considered to have three major portions: a core, an inner shell, and an outer shell. Ideally, a dendrimer can be synthesized to have different functionality in each of these portions to control properties such as solubility, thermal stability, and attachment of compounds for particular applications. Synthetic processes can also precisely control the size and number of branches on the dendrimer. There are two defined methods of dendrimer synthesis, divergent synthesis and convergent synthesis. However, because the actual reactions consist of many steps needed to protect the active site, it is difficult to synthesize dendrimers using either method. This makes dendrimers hard to make and very expensive to purchase. At this time, there are only a few companies that sell dendrimers; Polymer Factory Sweden AB commercializes biocompatible bis-MPA dendrimers and Dendritech is the only kilogram-scale producers of PAMAM dendrimers. NanoSynthons, LLC from Mount Pleasant, Michigan, USA produces PAMAM dendrimers and other proprietary dendrimers.
Dendrimer	Synthesis	Divergent methods The dendrimer is assembled from a multifunctional core, which is extended outward by a series of reactions, commonly a Michael reaction. Each step of the reaction must be driven to full completion to prevent mistakes in the dendrimer, which can cause trailing generations (some branches are shorter than the others). Such impurities can impact the functionality and symmetry of the dendrimer, but are extremely difficult to purify out because the relative size difference between perfect and imperfect dendrimers is very small.
Dendrimer	Synthesis	Convergent methods Dendrimers are built from small molecules that end up at the surface of the sphere, and reactions proceed inward building inward and are eventually attached to a core. This method makes it much easier to remove impurities and shorter branches along the way, so that the final dendrimer is more monodisperse. However dendrimers made this way are not as large as those made by divergent methods because crowding due to steric effects along the core is limiting.
Dendrimer	Synthesis	Click chemistry Dendrimers have been prepared via click chemistry, employing Diels-Alder reactions, thiol-ene and thiol-yne reactions and azide-alkyne reactions.There are ample avenues that can be opened by exploring this chemistry in dendrimer synthesis.
Dendrimer	Applications	Applications of dendrimers typically involve conjugating other chemical species to the dendrimer surface that can function as detecting agents (such as a dye molecule), affinity ligands, targeting components, radioligands, imaging agents, or pharmaceutically active compounds. Dendrimers have very strong potential for these applications because their structure can lead to multivalent systems. In other words, one dendrimer molecule has hundreds of possible sites to couple to an active species. Researchers aimed to utilize the hydrophobic environments of the dendritic media to conduct photochemical reactions that generate the products that are synthetically challenged. Carboxylic acid and phenol-terminated water-soluble dendrimers were synthesized to establish their utility in drug delivery as well as conducting chemical reactions in their interiors. This might allow researchers to attach both targeting molecules and drug molecules to the same dendrimer, which could reduce negative side effects of medications on healthy cells.Dendrimers can also be used as a solubilizing agent. Since their introduction in the mid-1980s, this novel class of dendrimer architecture has been a prime candidate for host–guest chemistry. Dendrimers with hydrophobic core and hydrophilic periphery have shown to exhibit micelle-like behavior and have container properties in solution. The use of dendrimers as unimolecular micelles was proposed by Newkome in 1985. This analogy highlighted the utility of dendrimers as solubilizing agents. The majority of drugs available in pharmaceutical industry are hydrophobic in nature and this property in particular creates major formulation problems. This drawback of drugs can be ameliorated by dendrimeric scaffolding, which can be used to encapsulate as well as to solubilize the drugs because of the capability of such scaffolds to participate in extensive hydrogen bonding with water. Dendrimer labs are trying to manipulate dendrimer's solubilizing trait, to explore dendrimers for drug delivery and to target specific carriers.For dendrimers to be able to be used in pharmaceutical applications, they must surmount the required regulatory hurdles to reach market. One dendrimer scaffold designed to achieve this is the polyethoxyethylglycinamide (PEE-G) dendrimer. This dendrimer scaffold has been designed and shown to have high HPLC purity, stability, aqueous solubility and low inherent toxicity.
Dendrimer	Applications	Drug delivery Approaches for delivering unaltered natural products using polymeric carriers is of widespread interest. Dendrimers have been explored for the encapsulation of hydrophobic compounds and for the delivery of anticancer drugs. The physical characteristics of dendrimers, including their monodispersity, water solubility, encapsulation ability, and large number of functionalizable peripheral groups make these macromolecules appropriate candidates for drug delivery vehicles.

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