Haemophilia is a inherited genetic disorder that impairs the body's ability to make blood clots, a process needed to stop bleeding. This results in people bleeding for a longer time after an injury, easy bruising, an increased risk of bleeding inside joints or the brain; those with a mild case of the disease may have symptoms only during surgery. Bleeding into a joint can result in permanent damage while bleeding in the brain can result in long term headaches, seizures, or a decreased level of consciousness. There are two main types of haemophilia: haemophilia A, which occurs due to low amounts of clotting factor VIII, haemophilia B, which occurs due to low levels of clotting factor IX, they are inherited from one's parents through an X chromosome carrying a nonfunctional gene. A new mutation may occur during early development or haemophilia may develop in life due to antibodies forming against a clotting factor. Other types include haemophilia C, which occurs due to low levels of factor XI, parahaemophilia, which occurs due to low levels of factor V.
Acquired haemophilia is associated with cancers, autoimmune disorders, pregnancy. Diagnosis is by testing its levels of clotting factors. Prevention may occur by removing an egg, fertilizing it, testing the embryo before transferring it to the uterus. Treatment is by replacing the missing blood clotting factors; this may be done during bleeding episodes. Replacement may take place in hospital; the clotting factors are made either by recombinant methods. Up to 20 % of people develop antibodies to the clotting factors; the medication desmopressin may be used in those with mild haemophilia A. Studies of gene therapy are in early human trials. Haemophilia A affects about 1 in 5,000–10,000, while haemophilia B affects about 1 in 40,000, males at birth; as haemophilia A and B are both X-linked recessive disorders, females are severely affected. Some females with a nonfunctional gene on one of the X chromosomes may be mildly symptomatic. Haemophilia C occurs in both sexes and is found in Ashkenazi Jews. In the 1800s haemophilia B was common within the royal families of Europe.
The difference between haemophilia A and B was determined in 1952. The word is from the Greek haima αἷμα meaning philia φιλία meaning love. Characteristic symptoms vary with severity. In general symptoms are internal or external bleeding episodes, which are called "bleeds". People with more severe haemophilia suffer more severe and more frequent bleeds, while people with mild haemophilia suffer more minor symptoms except after surgery or serious trauma. In cases of moderate haemophilia symptoms are variable which manifest along a spectrum between severe and mild forms. In both haemophilia A and B, there is spontaneous bleeding but a normal bleeding time, normal prothrombin time, normal thrombin time, but prolonged partial thromboplastin time. Internal bleeding is common in people with severe haemophilia and some individuals with moderate haemophilia; the most characteristic type of internal bleed is a joint bleed where blood enters into the joint spaces. This can occur spontaneously. If not treated promptly, joint bleeds can lead to disfigurement.
Bleeding into soft tissues such as muscles and subcutaneous tissues is less severe but can lead to damage and requires treatment. Children with mild to moderate haemophilia may not have any signs or symptoms at birth if they do not undergo circumcision, their first symptoms are frequent and large bruises and haematomas from frequent bumps and falls as they learn to walk. Swelling and bruising from bleeding in the joints, soft tissue, muscles may occur. Children with mild haemophilia may not have noticeable symptoms for many years; the first sign in mild haemophiliacs is heavy bleeding from a dental procedure, an accident, or surgery. Females who are carriers have enough clotting factors from their one normal gene to prevent serious bleeding problems, though some may present as mild haemophiliacs. Severe complications are much more common in cases of moderate haemophilia. Complications may arise from the disease itself or from its treatment: Deep internal bleeding, e.g. deep-muscle bleeding, leading to swelling, numbness or pain of a limb.
Joint damage from haemarthrosis with severe pain and destruction of the joint and development of debilitating arthritis. Transfusion transmitted infection from blood transfusions. Adverse reactions to clotting factor treatment, including the development of an immune inhibitor which renders factor replacement less effective. Intracranial haemorrhage is a serious medical emergency caused by the buildup of pressure inside the skull, it can cause disorientation, loss of consciousness, brain damage, death. Haemophilic arthropathy is characterized by chronic proliferative synovitis and cartilage destruction. If an intra-articular bleed is not drained early, it may cause apoptosis of chondrocytes and affect the synthesis of proteoglycans; the hypertrophied and fragile synovial lining while attempting to eliminate excessive blood may be more to rebleed, leading to a vicious cycle of hemarthrosis-synovitis-hemarthrosis. In addition, iron deposition in the synovium may induce an inflammatory response activating the immune system and stimulating angiogenesis, resulting in cartilage and bone destruction.
Females possess two X-chromosomes, males have one X and one Y-chromosome. Since the mutations caus
The pibgorn is a Welsh species of idioglot reed aerophone. The name translates as "pipe-horn", it is historically known as cornicyll and pib-corn. It utilises a single reed, cut from elder or reed, like that found in the drone of a bagpipe, an early form of the modern clarinet reed; the single chambered body of the elder pipe has a occurring parallel bore, into which are drilled six small finger-holes and a thumb-hole giving a diatonic compass of an octave. The body of the instrument is traditionally carved from a single piece of bone. Playable, extant historical examples in the Museum of Welsh Life have bodies cut and shaped of elder. Another, unplayable instrument at the Museum of a date, is made from the leg bone of an unspecified ungulate. Contemporary instruments are bored from a variety of fruitwoods, or exotic hardwoods; the reed is protected by a stock of cow-horn. The bell is shaped from a section of cow-horn; the pibgorn may be attached to a bag, with the additional possibility of a drone, called pibau cwd.
A double-pipe of unknown provenance, dated 1701 held by the Museum of Welsh Life has caused some controversy as to its possible Welsh or Mediterranean origin. The pipes in Wales, of which the pibgorn is a class, are mentioned in the laws of Hywel Dda; the earliest transcription of these dates from 1250 and specify that "the King should recognise the status of a Pencerdd in his service by giving him an appropriate instrument - either Harp, Crwth or Pipes." In modern Welsh orthography these three instruments are called telyn and pibau. Peniarth 20 c 1330, states that there are three types of wind instrument: "Organ, a Phibeu a Cherd y got", "organ, pipes and bag music". However, the instrument itself is older than these references, is part of a pattern of distribution of similar idioglot reedpipes and bag-hornpipes throughout Asia and North Africa that includes the "Old British pibcorn or hornpipe" alboka, arghul and others. William Morris writes in a letter to his brother the folklorist Richard Morris in 1759: " How pleasing it was to see the young farmworkers with their pibau cyrn under their arms....gathering the cows and piping'Mwynen Mai' and'Meillionnen’."According to Daines Barrington, who presented the pibgorn specimen shown at the Museum of Welsh life to Fellows of the Society of Antiquaries of London, an Anglesey landowner called Mr Wynn of Penhesgedd, offered an annual prize for pibgorn playing towards the end of the eighteenth century.
One such competition at Castellior Farm attracted 200 players. There is a further description by Siôn Wiliam Prichard of Christmas celebrations on the Castellior farm where the pibgorn and other instruments were played. Barrington described the tone of the instrument as played to him: "by one of the lads... considering the materials of which the pibgorn is composed is very tolerable"David Griffith recalls his father telling him that "playing the Pibgorn was a common thing in those days in the South and that farmers' servant men were in the habit of carrying them with them when driving cattle to the fairs." The Reverend Meredith Morris of The Gwaun Valley in Pembrokeshire writes in his autobiography in 1910: "Mabsantau, gwylnosau, &c, were their red-letter days, the rude merrimaking of the village green the pivot of all, worth living for in a mundane existence. I do not remember much about the Gwylmabsant and the Gwylnos - I came a quarter of a century too late for those wonderful orgies - but I remember the neithior with its all-day and all-night rollicking fun.
We did not have the crwth, but we had the fiddle, the harp, or a home-made degenerate sort of pibgorn. I myself am a tolerable player on the simplified bibgorn." After a hiatus of fifty years, the pibgorn, alongside instruments such as the crwth and the triple harp, has witnessed a resurgence in popularity as part of a general revival of interest in Welsh folk music. Some modern instruments play a tempered scale to accommodate fixed pitch instruments such as guitar or keyboard, are pitched in D. Historical instruments play in a variety of pitch. Jonathan Shorland, after measuring and playing the instruments in co-operation with the then-keeper of instruments, D. Roy Saer, at the Museum of Folk Life in Wales, concluded that the instrument made of bone was no longer playable due to splitting. Of the two elder pipes, The shorter instrument gave a six-finger key note near to F and played a scale close to the Locrian mode; the longer instrument gave a six-finger key note near to an unnamed mode. Shorland noted that the finger hole for the sixth note was shaped differently and was smaller than the rest, that the flat note was intentional.
Contemporary pibgorn makers in Wales include Jonathan Shorland, John Tose, John Glennydd, Keith Lewis, Gafin Morgan, Gerard KilBride. In Scotland, Julian Goodacre. In the United States. Contemporary repertoire makes use of folksong and Hymn tunes adapted to the instrument and printed collections of dance music that may be adapted to fit the instrument's
"... In Translation" is the 17th episode of the first season of the American drama television series Lost; the episode was directed by Tucker Gates and written by Javier Grillo-Marxuach and producer Leonard Dick. It first aired on ABC in the United States on February 23, 2005; the character of Jin-Soo Kwon is featured in the episode's flashbacks, revealing his disturbing job experience under Mr. Paik, the father of his wife Sun-Hwa Kwon. In the present, Michael's unfinished raft catches fire overnight, leading him and Sawyer to blame Jin for the incident; the episode title is a reference to the phrase "lost in translation", where a phrase or idiom loses its meaning when translated between languages. "... In Translation" was seen by an estimated 19.49 million American household viewers. It received mixed-to-positive reviews from critics, with praise given to the episode developing the characters of Jin and Sun, while the lack of progress in the series' narrative was criticized. Jin-Soo Kwon visits Mr. Paik, to ask for his daughter's hand in marriage.
Mr. Paik asks Jin about his family. Jin states that he would like to own his own restaurant and hotel, that his father is deceased, as well as telling Mr. Paik that he would do anything for Sun. Mr. Paik is unspecific about its requirements. Jin tells Sun that they will be able to go on their honeymoon after he does some management training. Jin gets promoted and Mr. Paik assigns him to go to the house of the Secretary for Environmental Safety, Byung Han, to "deliver a message" regarding Mr. Paik's disappointment with Han's decision to close the factory. There, he tells Mr. Han; as a way to make Mr. Paik happy, Mr. Han gives Jin a puppy, the same dog seen earlier in Sun's flashbacks. Sun prepares a candlelit dinner for her husband, but they are interrupted by Mr. Paik, upset that his factory has been closed. Mr. Paik blames Jin for not delivering the message properly - Jin didn't understand that he was being asked to threaten the secretary. Mr. Paik sends Jin, along with a mercenary companion wielding a silenced pistol, back to Mr. Han's house.
To save the man's life, Jin brutally beats up Mr. Han right in front of young daughter, he tells him that the factory must open tomorrow, tells the mercenary Mr. Han got the message, he returns home and washes blood from his hands, but this scene is now followed with Jin crying for what he has been forced to do. Jin visits his father in a fishing village, revealing that Jin lied about his father being dead to Mr. Paik, begs for forgiveness for being ashamed of him, his father embraces him. They talk about the marital difficulties, Jin expresses his wish to "start over". After commenting that Mr. Paik's next job for Jin is to go sell watches to his associates in Sydney and Los Angeles, Jin is told by his father to go to America with Sun to start a new life. On Day 32, October 23, 2004, Sun is wearing a bikini. Jin shoves her into the sand. Michael Dawson threatens Jin. Sun slaps Michael in the face, he stands there shocked as Sun walk away. As Sun dresses, Jin asks if she is involved with Michael and she says no.
Sun apologizes to Michael for slapping him. She said that she did it to protect Michael, because he doesn't know what Jin can do, implying her slapping him saved him from a far worse beating. Shannon Rutherford and Sayid Jarrah flirt. Jack Shephard comes over and Michael tells him the raft can only fit four people. Jack asks about the available spots on the raft and Sawyer says that he bought one in exchange for some building materials. At night the raft catches fire and all the islanders, namely Michael and Sawyer, angrily blame Jin. Sun finds Jin covered with burns and he does not speak to her. Sayid informs Shannon's stepbrother, Boone Carlyle, that he may be dating Shannon, Boone warns him that she is using him; the next day, Sayid tells Shannon. Shannon runs into Locke instead, he advises her to start a new life rather than confront Boone. Sawyer knocks him out with a kick to the head, he escorts him to the beach. Back at the beach, Michael beats Jin up; as the beating intensifies, Sun surprises everyone, including Jin, by revealing for the first time publicly that she can speak English.
Locke quells the growing argument by stating that it would be unlikely that one of the survivors burned the raft, suggesting that "the Others" are responsible and that they aren't alone on the island. Michael decides to make a new raft. Sun goes to see Jin and says that she was going to leave him and that he changed her mind about leaving. Speaking Korean, she asks him if they can "start all over". However, Jin tells her. At night, Shannon decides to stay with Sayid though Boone does not like Sayid around her. Locke reveals that he knows Walt burnt the raft when he asks him why he did it, though he promises not to tell anyone. Walt replies by stating that he doesn’t want to move anymore, that he likes it on th
Dimitrios Chasiotis is a Greek former swimmer, who specialized in backstroke events. He represented his nation Greece at the 2008 Summer Olympics, swam for Olympiacos in Athens. Chasiotis competed as part of the Greek swimming squad in the men's 200 m backstroke at the 2008 Summer Olympics in Beijing. Three months before the Games, he smashed both a national record on a bodysuit and a FINA B-cut of 1:59.95 at the Akropolis Grand Prix in Athens, clipping off a previous standard from former Olympian Antonios Gkioulmpas by a few seconds. Chasiotis rounded out the field to last place and thirty-sixth overall in heat three of the evening prelims with 2:02.30, just two seconds slower than his entry time. NBC Olympics Profile
Yves Jeuland is a French author and director of more than thirty documentary films made for television and cinema, alternating archival and direct cinema films. Many of his films are about political engagement or the practice of power. In particular, he traces the history of the French communists in Camarades in 2004, or of the French socialists in Le siècle des Socialistes in 2005. Before that, he followed, between 1999 and 2001, Bertrand Delanoë, for the Parisian municipal election in Paris à tout prix In 2010, for cinema, he directed Le Président where he filmed Georges Frêche during his last political campaign. In 2014, he has directed Un temps de président, a documentary on the daily of the French president François Hollande, his work based on archival images has been rewarded several times: in 2007 his film Comme un Juif en France a three-hour documentary on the history of Jews and anti-Semitism in France from the 19th century to the present day won the Lia Award of Jerusalem Film Festival.
In 2013 and in 2017, he won the prize for the best television documentary by the French Syndicate of Cinéma Critics. Once for Il est minuit, Paris s'éveille - on post-war Parisian nights with the testimonies of Jean Rochefort, Juliette Greco or Charles Aznavour, etc; the second time for Un Français nommé Gabin, a long portrait composed of archives and extracts of films, on the career and the life of Jean Gabin. This film was selected for the French Film Festival, he has directed Bleu, rose on the history of the French gay movement. His movie Les gens du Monde, about the work of the journalists of the daily newspaper Le Monde was part of the Official Selection of the 2014 Cannes Film Festival. 1998: Ombres de cristal 2001: Paris à tout prix, about the Paris municipal election in 2001. Best documentary by 7 d'Or 2002: Bleu, rose 2004: La Paix nom de Dieu! Shot in Israel and Palestine in 2003 2004: Camarades, il était une fois les communistes français 2004: Maris à tout prix 2005: Le Siècle des socialistes 2007: Comme un juif en France, dans la joie ou la douleur - Lia Award of Jerusalem Film Festival 2007: Parts de Marchais, Georges le cathodique 2008: Un village en campagne 2010: Les Compagnons de l'aube about the Free France 2010: Le Président about the last campaign of Georges Frêche 2012: Il est minuit, Paris s'éveille about the Parisian night life of cabarets after the WW2.
Price 2013 of the best documentary by the French Syndicate of Cinéma Critics. 2013: Delanoë libéré' 2014: Les Gens du Monde 2015: Un temps de président, about the French President François Hollande 2017: L'extravagant Monsieur Piccoli 2017: Un Français nommé Gabin. Price 2017 of the best documentary by the French Syndicate of Cinéma Critics; the film was selected for the French Film Festival. 2018: La Vie balagan de Marceline Loridan-Ivens Yves Jeuland on IMDb
Glutaredoxin 2 is an enzyme that in humans encoded by the GLRX2 gene. GLRX2 known as GRX2, is a glutaredoxin family protein and a thiol-disulfide oxidoreductase that maintains cellular thiol homeostasis; this gene consists of four exons and three introns, spanned 10 kilobase pairs, localized to chromosome 1q31.2–31.3. Alternative splicing of GLRX2 leads to three isoforms of Grx2. One isoform, Grx2a, localizes to the mitochondria, is ubiquitously expressed in tissues, regulates mitochondrial redox homeostasis, protects cells against oxidative stress. Isoforms Grx2b and Grx2c, both localized to the nucleus and cytosol, are expressed only in testes and cancer cell lines and facilitate cellular differentiation and transformation inducing tumor progression; the transcripts of mitochondrial and nuclear Grx2 isoforms, Grx2a and Grx2b differ in the first exon, with the exon 1 in Grx2b located upstream of that in Grx2a. Grx2c is derived from alternative splicing of the Grx2b transcript with a shorter exon 1 than that of Grx2b.
As a GRX family protein, Grx2 has an N-terminal thioredoxin domain, possessing a 37CSYC40 active site motif with a serine residue replacing the conserved proline residue. This amino acid substitution allows the main chain of Grx2 to be more flexible, promoting coordination of the iron-sulfur cluster and facilitating deglutathionylation by enhanced glutathione-binding; the cysteine pair falls outside of the active site, it is conserved in Grx2 proteins but not found in some other GRX family proteins. A disulfide bond between this cysteine pair increases structural stability and provides resistance to over-oxidation induced enzymatic inactivation. Grx2 functions as a part of the cellular redox signaling pathway and antioxidant defense mechanism; as a GRX family protein, Grx2 acts. It has been shown to reduce both thioredoxin 2 and thioredoxin 1 and protects cells from apoptosis induced by auranofin and 4-hydroxynonenal. Grx2 is an electron acceptor, it can catalyze the reversible oxidation and glutathionylation of mitochondrial membrane thiol proteins.
Additionally, NADPH and thioredoxin reductase efficiently reduce both the active site disulfide of Grx2 and the GSH-Grx2 intermediate formed in the reduction of glutathionylated substrates. Enzymatic activity of Grx2 leads to its role in regulating redox-induced apoptosis. Grx2 over-expression protects cells against H2O2-induced damage while Grx2 knockdown showed the opposite effect; the protection role of Grx2 against H2O2-induced apoptosis is associated with its ability to preserve the electron transport chain complex I. In addition to H2O2, Grx2a overexpression is resistant to apoptosis induced by other oxidative stress reagents, due to reduced cardiolipin oxidation and subsequent cytochrome c release. Interesting, Grx2 has been found to prevent aggregation of mutant SOD1 in mitochondria and abolish its toxicity. Being a redox sensor, Grx2 activity is regulated by the oxidative state of the environment via iron-sulfur cluster. In steady state, Grx2 forms dimers to coordinate iron-sulfur clusters, which in turn inactivate Grx2’s activity by sequestering the active-site cysteines.
During oxidative stress, the dimers separate into iron-free active monomers, which restore Grx2’s activity. From 42 cases of non-small cell lung cancer patients, the expression level of Grx2 showed a significant correlation with the degree of differentiation in adenocarcinoma and a clear inverse correlation with proliferation. In tumor cells, cells with decreased Grx2 are sensitized to cell death induced by the anti-cancer drug, DOX. In cardiovascular disease, Grx2a overexpression protects mouse heart from Dox and ischemia-induced cardiac injury via increasing mitochondrial protein glutathionylation. Conversely, Grx2 knockout hearts developed left ventricular hypertrophy and fibrosis, leading to hypertension; the mechanistic study shows that Grx2 knockout decreased mitochondrial ATP production via increased glutathionylation and thereby inhibition of complex I. Grx2 has been shown to physically interact with MDH2, PITPNB, GPX4, CYCS, BAG3, TXNRD1 in one independent high-throughput proteomic analysis