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Jan Potocki
Count Jan Potocki (; 8 March 1761 – 23 December 1815) was a Polish nobleman, Polish Army Captain of Engineers, ethnologist, Egyptologist, linguist, traveler, adventurer, and popular author of the Enlightenment period, whose life and exploits made him a legendary figure in his homeland.
Outside Poland he is known chiefly for his novel, "The Manuscript Found in Saragossa".
Jan Potocki was born into the Potocki aristocratic family, that owned vast estates across Poland.
He was educated in Geneva and Lausanne, served twice in the Polish Army as a captain of engineers, and spent some time on a galley as novice to the Knights of Malta.
His colorful life took him across Europe, Asia and North Africa, where he embroiled himself in political intrigues, flirted with secret societies and contributed to the birth of ethnology – he was one of the first to study the precursors of the Slavic peoples from a linguistic and historical standpoint.
In 1790 he became the first person in Poland to fly in a hot air balloon when he made an ascent over Warsaw with the aeronaut Jean-Pierre Blanchard, an exploit that earned him great public acclaim.
He spent some time in France, and upon his return to Poland, he became a known publicist, publishing newspapers and pamphlets, in which he argued for various reforms.
He also established in 1788 in Warsaw a publishing house named "Drukarnia Wolna" (Free Press) as well as the city's first free reading room.
His relation with the King Stanisław II August was thorny, as Potocki, while often supportive of the King, on occasion did not shy from his critique.
He was highly critical of the Russian ambassador, Otto Magnus von Stackelberg.
Potocki's wealth enabled him to travel extensively about Europe, the Mediterranean and Asia, visiting Italy, Sicily, Malta, the Netherlands, Germany, France, England, Russia, Turkey, Dalmatia, the Balkans, the Caucasus, Spain, Tunisia, Morocco, Egypt, and even Mongolia.
He was also one of the first travel writers of the modern era, penning lively accounts of many of his journeys, during which he also undertook extensive historical, linguistic, and ethnographic studies.
Potocki married twice and had five children.
His first marriage ended in divorce, and both marriages were the subject of scandalous rumors.
In 1812, disillusioned and in poor health, he retired to his estate at Uładówka in Podolia, suffering from "melancholia" (which today would probably be diagnosed as depression), and during the last few years of his life he completed his novel.
Believing he was becoming a werewolf, Potocki committed suicide by fatally shooting himself with a silver bullet that he had had blessed by his village priest in December 1815, at the age of 54.
Potocki's most famous work, originally written in French, is "The Manuscript Found in Saragossa" ("Manuscrit trouvé à Saragosse").
It is a frame tale.
On account of its rich, interlocking structure, and telescoping story sequences, the novel has drawn comparisons to such celebrated works as the "Decameron" and the "Arabian Nights".
The book's title is explained in the foreword, which is narrated by an unnamed French officer who describes his fortuitous discovery of an intriguing Spanish manuscript during the sack of Zaragoza in 1809, in the course of the Napoleonic Wars.
Soon after, the French officer is captured by the Spanish and stripped of his possessions; but a Spanish officer recognizes the manuscript's importance, and during the French officer's captivity the Spaniard translates it for him into French.
The manuscript has been written by a young officer of the Walloon Guard, Alphonse van Worden.
In 1739, while "en route" to Madrid to serve with the Spanish Army, he is diverted into Spain's rugged Sierra Morena region.
There, over a period of sixty-six days, he encounters a varied group of characters, including Muslim princesses, Gypsies, outlaws, and cabbalists, who tell him an intertwining series of bizarre, amusing, and fantastic tales which he records in his diary.
The sixty-six stories cover a wide range of themes, subjects, and styles, including gothic horror, picaresque adventures, and comic, erotic, and moral tales.
The stories reflect Potocki's interest in secret societies, the supernatural, and oriental cultures, and they are illustrated with his detailed observations of 18th-century European manners and customs, particularly those of upper-class Spanish society.
Many of the locations described in the tales are real places and regions which Potocki would have visited during his travels, while others are fictionalized accounts of actual places.
While there is still some dispute about the novel's authorship, it is now generally accepted to have indeed been written by Potocki.
He began writing it in the 1790s and completed it in 1814, a year before his death, though the novel's structure is thought to have been fully mapped out by 1805.
The novel was never published in its entirety during Potocki's lifetime.
A proof edition of the first ten "days" was circulated in Saint Petersburg in 1805, and a second extract was published in Paris in 1813, almost certainly with Potocki's permission.
A third publication, combining both earlier extracts, was issued in 1814, but it appears that at the time of his death Potocki had not yet decided on the novel's final form.
Potocki composed the book entirely in the French language.
Sections of the original manuscripts were later lost, but have survived in a Polish translation that was made in 1847 by Edmund Chojecki from a complete French copy, now lost.
The most recent and complete French-language version, edited by François Rosset and Dominique Triaire, was published in 2006 in Leuven, Belgium, as part of a critical scholarly edition of the complete works of Potocki.
Unlike Radrizzani's 1989 edition of the "Manuscript Found in Saragossa", Rosset and Triaire's edition has been based solely on Potocki's French-language manuscripts found in several libraries in France, Poland (in particular, previously unknown autograph pieces that they discovered in Poznań), Spain, and Russia, as well as in the private collection of Potocki's heirs.
They identified two versions of the novel: one unfinished, of 1804, published in 1805, and the full version of 1810, which appears to have been completely reconceived in comparison to the 1804 version.
Whereas the first version has a lighter, more sceptical tone, the second one tends towards a darker, more religious mood.
In view of the differences between the two versions, the 1804 and 1810 versions have been published as two separate books; paperback editions were issued in early 2008 by Flammarion.
The first English-language edition, published in 1995, was a translation of Radrizzani's edition by Oxford scholar Ian Maclean.
Potocki's novel became more widely known in the West via the stylish black-and-white film adaptation made in Poland in 1965 as "The Saragossa Manuscript" ("Rękopis znaleziony w Saragossie"), directed by renowned filmmaker Wojciech Has and starring Zbigniew Cybulski as Alphonse van Worden.
Modern editions have appeared as follows:
Granulocyte colony-stimulating factor
Granulocyte-colony stimulating factor (G-CSF or GCSF), also known as colony-stimulating factor 3 (CSF 3), is a glycoprotein that stimulates the bone marrow to produce granulocytes and stem cells and release them into the bloodstream.
Functionally, it is a cytokine and hormone, a type of colony-stimulating factor, and is produced by a number of different tissues.
The pharmaceutical analogs of naturally occurring G-CSF are called filgrastim and lenograstim.
G-CSF also stimulates the survival, proliferation, differentiation, and function of neutrophil precursors and mature neutrophils.
G-CSF is produced by endothelium, macrophages, and a number of other immune cells.
The natural human glycoprotein exists in two forms, a 174- and 177-amino-acid-long protein of molecular weight 19,600 grams per mole.
The more-abundant and more-active 174-amino acid form has been used in the development of pharmaceutical products by recombinant DNA (rDNA) technology.
The gene for G-CSF is located on chromosome 17, locus q11.2-q12.
Nagata et al.
found that the GCSF gene has 4 introns, and that 2 different polypeptides are synthesized from the same gene by differential splicing of mRNA.
The 2 polypeptides differ by the presence or absence of 3 amino acids.
Expression studies indicate that both have authentic GCSF activity.
It is thought that stability of the G-CSF mRNA is regulated by an RNA element called the G-CSF factor stem-loop destabilising element.
Chemotherapy can cause myelosuppression and unacceptably low levels of white blood cells (leukopenia), making patients susceptible to infections and sepsis.
G-CSF stimulates the production of granulocytes, a type of white blood cell.
In oncology and hematology, a recombinant form of G-CSF is used with certain cancer patients to accelerate recovery and reduce mortality from neutropenia after chemotherapy, allowing higher-intensity treatment regimens.
It is administered to oncology patients via subcutaneous or intravenous routes.
A QSP model of neutrophil production and a PK/PD model of a cytotoxic chemotherapeutic drug (Zalypsis) have been developed to optimize the use of G-CSF in chemotherapy regimens with the aim to prevent mild-neutropenia.
G-CSF was first trialled as a therapy for neutropenia induced by chemotherapy in 1988.
The treatment was well tolerated and a dose-dependent rise in circulating neutrophils was noted.
A study in mice has shown that G-CSF may decrease bone mineral density.
G-CSF administration has been shown to attenuate the telomere loss associated with chemotherapy.
Neutropenia can be a severe side effect of clozapine, an antipsychotic medication in the treatment of schizophrenia.
G-CSF can restore neutrophil count.
Following a return to baseline after stopping the drug, it may sometimes be safely rechallenged with the added use of G-CSF.
G-CSF is also used to increase the number of hematopoietic stem cells in the blood of the donor before collection by leukapheresis for use in hematopoietic stem cell transplantation.
For this purpose, G-CSF appears to be safe in pregnancy during implantation as well as during the second and third trimesters.
Breastfeeding should be withheld for 3 days after CSF administration to allow for clearance of it from the milk.
People who have been administered colony-stimulating factors do not have a higher risk of leukemia than people who have not.
G-CSF may also be given to the receiver in hematopoietic stem cell transplantation, to compensate for conditioning regimens.
The skin disease Sweet's syndrome is a known side effect of using this drug.
Mouse granulocyte-colony stimulating factor (G-CSF) was first recognised and purified in Walter and Eliza Hall Institute, Australia in 1983, and the human form was cloned by groups from Japan and Germany/United States in 1986.
The FDA approved the first biosimilar of Neulasta in June 2018.
It is made by Mylan and sold as Fulphila.
The recombinant human G-CSF (rhG-CSF) synthesised in an "E. coli" expression system is called filgrastim.
The structure of filgrastim differs slightly from the structure of the natural glycoprotein.
Most published studies have used filgrastim.
Filgrastim was first marketed by Amgen with the brand name Neupogen.
Several bio-generic versions are now also available in markets such as Europe and Australia.
Filgrastim (Neupogen) and PEG-filgrastim (Neulasta) are two commercially available forms of rhG-CSF.
The PEG (polyethylene glycol) form has a much longer half-life, reducing the necessity of daily injections.
Another form of rhG-CSF called lenograstim is synthesised in Chinese Hamster Ovary cells (CHO cells).
As this is a mammalian cell expression system, lenograstim is indistinguishable from the 174-amino acid natural human G-CSF.
No clinical or therapeutic consequences of the differences between filgrastim and lenograstim have yet been identified, but there are no formal comparative studies.
G-CSF when given early after exposure to radiation may improve white blood cell counts, and is stockpiled for use in radiation incidents.
Mesoblast planned in 2004 to use G-CSF to treat heart degeneration by injecting it into the blood-stream, plus SDF (stromal cell-derived factor) directly to the heart.
G-CSF has been shown to reduce inflammation, reduce amyloid beta burden, and reverse cognitive impairment in a mouse model of Alzheimer's disease.
Due to its neuroprotective properties, G-CSF is currently under investigation for cerebral ischemia in a clinical phase IIb and several clinical pilot studies are published for other neurological disease such as amyotrophic lateral sclerosis A combination of human G-CSF and cord blood cells has been shown to reduce impairment from chronic traumatic brain injury in rats.
Sundaland
Sundaland (also called the Sundaic region) is a biogeographical region of Southeastern Asia corresponding to a larger landmass that was exposed throughout the last 2.6 million years during periods when sea levels were lower.
It includes the Malay Peninsula on the Asian mainland, as well as the large islands of Borneo, Java, and Sumatra and their surrounding small islands.
The area of Sundaland encompasses the Sunda Shelf, a tectonically stable extension of Southeast Asia's continental shelf that was exposed during glacial periods of the last 2 million years.
The extent of the Sunda Shelf is approximately equal to the 120 meter isobath.
In addition to the Malay Peninsula and the islands of Borneo, Java, and Sumatra, it includes the Java Sea, the Gulf of Thailand, and portions of the South China Sea.
In total, the area of Sundaland is approximately 1,800,000 km, The area of exposed land in Sundaland has fluctuated considerably during the past recent 2 million years; the modern land area is approximately half of the maximum extent.