Hillel Yaffe

Hillel Yaffe (1864–1936) () was a Russian Jewish physician and Zionist leader who immigrated to Palestine during the First Aliyah. He was instrumental in curing malaria among the Jewish population of Palestine in the early 20th century, and helped improve the medical infrastructure of the Yishuv during the same period. The Hillel Yaffe Medical Center in Hadera is named after him.
Biography.
Hillel Yaffe was born in 1864 in a small village in the Ukraine. His father was a merchant and a man of means, who provided his son with a traditional Jewish education. When he grew up, Yaffe was sent to learn in a secondary school in order to expand his horizons. These studies encouraged him to study medicine and brought him close to the Zionist movement. When he finished secondary school, he traveled to Geneva, where he began to study medicine. Afterward he specialized in eye care in Paris. He began to publish laboratory work in his field of expertise, and his research was respected in the scientific community. Yaffe's decision to specialize in medicine, especially in eye care, derived from his dream to become a doctor in the Land of Israel. In 1891, he traveled to Turkey, the seat of the Ottoman Empire, where he received a license to practice medicine. From there, he sailed to Jaffa.
Yaffe married Rivka Glickstein in 1898. She was the sister of Esther Glickstein, who would later marry . Before they met, Rivka had studied with Yaffe's sister in France. The couple had three children: Yirmeyahu, Sarah and Ya'akov. Yirmeyahu served as a captain in the Jewish Brigade, and after World War I he earned a doctorate in chemistry. Sarah studied agriculture in England and married Joseph Bentwich, who earned the Israel Prize for education in 1962. Ya'akov, who learned medicine and specialized in tropical diseases, lived in Jerusalem as of 2007. His nephew, Yigael Gluckstein who wrote under the name Tony Cliff, was a Palestinian Jewish Trotskyist and the founder of the British Socialist Workers Party.
Medical career.
After traveling around the country, Yaffe settled in Tiberias. He worked as a doctor there for two years (1891–1893) and then moved to Zikhron Ya'akov. He was noted especially for his dedicated work for the people of Hadera, who were suffering from malaria. He visited the moshava of Hadera at least twice a week and succeeded to heal some of the men, but the mortality rate remained high. Slowly it became apparent that a fundamental, broad program would be necessary to remove the scourge of malaria from the Jewish settlement, since individual treatment was insufficient. In 1895, two years after he became the doctor of Zikhron Ya'akov, Yaffe received a nomination to become the representative of Hovevei Zion in Israel. This nomination opened a new chapter in Yaffe's life.
Zionist leadership.
Yaffe's decision to combine medicine with political activism derived from his realization that in order to fulfill his mission for the Jewish settlement in Israel, it was necessary to form new institutions. Yaffe understood that in order to succeed in eradicating malaria, he needed to combine practical treatment of patients with research, community activism, and politics. When Yaffe accepted this job, he moved to Jaffa, which was a central city, and managed to raise money to drain the infested swamp near Hadera. He traveled to Europe to raise money for various purposes such as saving the first Hebrew school, which was on the verge of financial collapse.
Yaffe became a noted authority on malaria, its prevention and its cure. He published many articles and even lectured in Paris in an international conference on malaria in 1900. He worked to improve public health and studied other illnesses which had spread throughout the region, with an emphasis on prevention and minimizing contagious spreading of diseases. In 1902, an epidemic of cholera spread through Israel. Yaffe was appointed by the Turkish government to combat the epidemic. He decided that people were forbidden to leave their communities, and that it was forbidden to enter or leave the house of a sick person, in order to stop the illness from spreading. The epidemic was stopped.
In 1903 Yaffe participated in a delegation of the Zionist movement to investigate the El-Arish region, a prospective location for a Jewish state suggested by Theodor Herzl at the Zionist Congress. In the same year, representatives of Zikhron Ya'akov gathered and established the General Union and Teachers' Union of the Yishuv. Yaffe stood as their head and worked to establish the resources of the communities so that they would not need to rely on external financial support. He also worked to convince the groups who worked in education to use the Hebrew language.
In 1905, Yaffe abandoned Hovevei Zion and began to work in the Jaffa hospital. During his work he became sick with pneumonia and traveled to Europe to heal. In 1907 he returned to Israel and began to run the hospital in Zikhron Ya'akov. Yaffe's extensive knowledge of the importance of public health and the practical realities of Israel led him to build a widespread system of prevention. He trained crews of medics who could help settlers, and these crews spread throughout the land and improved the level of prevention and treatment in the population.
In 1919, he moved from Zikhron Ya'akov to Haifa, where he worked as a doctor and published articles on medicine. His articles were published in newspapers outside the country, and he was invited to international medical conferences. Yaffe continued to work until his death in 1936. He was buried, according to his wishes, in Zikhron Ya'akov.
Fight against malaria.
Yaffe's first efforts to eradicate malaria focused on drying the swamps. He used many methods, including wide use of eucalyptus trees, on the principle that the large tree would draw a lot of water from the ground. Also, manual efforts were undertaken to dry the swamps. The residents of Hadera and foreign workers from Africa (who arrived after Yaffe requested help from Baron Rothschild) began the physically demanding labor of drying the swamps using a wide network of canals, connecting the swamps to the Hadera Stream. Another approach taken by Yaffe was research. Yaffe left for Europe and learned novel theories about malaria. Among these studies was one that suggested that mosquitoes from the genus Anopheles, which were prevalent in swamps, were carriers of the disease. He began to plead with farmers to hang canopies around the beds, nets around the windows, and to clean every pool of standing water. Likewise, Yaffe convinced Baron Rothschild to send men to kill the mosquitoes. Afterward the incidence of malaria decreased, and efforts to dry the swamps continued with greater force. Forestation of large areas near Hadera with eucalyptus trees was part of Yaffe's effort to change the environment in order to respond comprehensively to the disease.


Edward Sayers (parasitologist)

Sir Edward George Sayers (10 September 190212 May 1985) was a New Zealand doctor, parasitologist, Methodist missionary, military medical administrator, consultant physician and, from 1958 to 1968, Dean of the University of Otago, School of Medicine. Having trained as a doctor, from 1927 to 1934 he worked at the Methodist mission in the Solomon Islands where he carried out fieldwork in the treatment of malaria. The significance of this work became apparent when Sayers used his knowledge to reduce deaths of American, Australia and New Zealand military forces during the invasion of Pacific Islands during World War II. He served as a doctor with the 2nd Division 2 NZEF during 1941–42 in Greece and North Africa. In 1942 he was transferred to the Pacific to serve with the 3rd Division, 2 NZEF IP.
His 1943 handbook on malaria control, "Malaria in the South Pacific", became a standard text. As a specialist in tropical diseases (malaria, dengue fever, sand-fly fever and dysentery) his work contributed to minimising deaths in the New Zealand army. The pre-war experience and malaria records of Sayers was also helpful to the United States forces in reducing malaria rates during the Solomon Islands campaign. His contribution was acknowledged by the award of the Legion of Merit by the United States.
Early life.
Sayers was born in New Brighton, Christchurch, on 10 September 1902. His mother was Amelia Ruth Blandford; his father was Henry Hind Sayers, a cabinet maker from Sussex, England, who suffered from T.B. spine and became paraplegic after an accident. Sayers' brothers were Stanley, Harry and Charles.
He won a scholarship to Christ's College, Christchurch where he remained until he was 15, when family circumstances caused him to leave. He worked for two years as a clerk.
Medical training.
With the assistance of his church Sayers was able to attend university. He studied at the University of Otago Dunedin School of Medicine and graduated MB ChB in 1924. He spent a year as a house physician at Wellington Hospital, and then gained further training at the London School of Hygiene & Tropical Medicine, where he received a diploma in tropical medicine in 1926.
Methodist missionary in the Solomon Islands.
From 1927 to 1934 he worked at the Methodist mission in the Solomon Islands. On 3 March 1928, at Roviana in New Georgia, Solomon Islands, Sayers married Jane Lumsden Grove; they had six children: two sons, John and Edward; and four daughters, Kathleen, Margaret, Nancy and Pamela. Sayers set up hospitals at Gizo, Munda and Vella Lavella in the Western Province of the Solomon Islands.
The Methodist Mission in the Western Province in the New Georgia Islands around the Roviana lagoon had been established by Rev. John Francis Goldie in 1902. He dominated the mission and gained the loyalty of Solomon Islander members of his church, although he had an autocratic approach to the management of his subordinates. The relationship with the colonial administrators of the British Solomon Island Protectorate were also fraught with difficulty due to Goldie's effective control over the Western Solomon Islands. Navigating these complicated relationships give Sayers valuable management skills, which he would later apply as a military medical administrator and university dean. However it was the knowledge as to the treatment of malaria and other tropical diseases that Sayers gained from setting up hospitals in the Solomons that he later applied during his service as a physician with the New Zealand General Hospital that was part of the New Zealand Expeditionary Force during World War II. Sayers also identified that an effective treatment of tropical ulcers was the application of non-adherent dressings; he used the recently developed sticking plaster tape. On reporting his findings Beiersdorf, the manufacturer of "Elastoplast", sent him a year's supply.
In 1934 Sayers went to London with his family. In 1935 Sayers gained membership of the Royal College of Physicians of London (MRCP). He and his family returned to New Zealand, where he established himself as a medical consultant in Auckland and he was appointed to the visiting staff of the Auckland Hospital. In 1938 he was a foundation fellow of the Royal Australasian College of Physicians (RACP).
Service as military medical administrator.
Following the outbreak of war, Sayers enlisted with the rank of captain and on 1 May 1940 he was sent to the Middle East with No. 1 New Zealand General Hospital, as a physician and adviser on tropical medicine. In 1941 the 2nd Division 2 NZEF, was engaged in the retreat from Greece to Crete to North Africa.
In early April 1941 No. 1 General Hospital was located at Pharsala (Pharsalos or Pharsalus) now known as Farsala. In the chaotic withdrawal of troops from Greece the sisters, staff, and patients of No. 1 General Hospital were to be evacuated from the port of Piraeus. The officers and men embarked on "MV Rawnsley" on 19 April, but the ship missed its convoy and was machine-gunned and bombed by German aircraft. Captains Sayers and King accompanied the nurses, although they actually took much longer to leave Greece than the officers and men; the nurses expect to join the hospital ship "Aba", but it left Piraeus before the designated time to avoid air attacks. The "MV Rawnsley" and the hospital ship "Aba" arrived in Alexandria on 23 April 1941. The nursing sisters, with Captains Sayers and King, arrived in Cairo on 1 May 1941, having travelled via Crete.
As a consequence of the loss of medical personnel in 2 NZEF during the Greece campaign, No. 1 General Hospital was not reformed as an active hospital until new personnel arrived. On 10 August 1941 Sayers, promoted to major, was placed in charge of the medical division of No. 1 General Hospital, which was located in the Cairo zone at Helwan, with the hospital acting as a base hospital during the North African campaigns of 1941–42.
Sayers was promoted to lieutenant-colonel and in November 1942 he was transferred from the Middle East to the Pacific to take charge of the medical division of No. 4 New Zealand General Hospital which was deployed to New Caledonia. As the consultant in tropical diseases, Sayers identified that providing a solution to the malaria problem was an important element in the conduct of the Pacific war. The anti-malarial precautions and training given to the New Zealand soldiers in the Solomon Islands campaign resulted in a low sickness rate from malaria of 3.19 per cent of the troops that entered zones in which malaria was prevalent. Sayers' contribution to the minimisation of deaths from malaria is acknowledged in the Official Histories of World War 2 of the New Zealand Forces and of the United States. His contribution to the American forces was acknowledged by the award of the Legion of Merit (U.S).
Career in medical education.
At the end of the Pacific war, Sayers returned to Auckland where he was a physician in private practice and consultant to the Auckland Hospital. He carried out research into pollen-based allergies and produced serums to counteract the effect of these pollens; he had an extensive patient list of asthmatics in Auckland.
In the 1950s he became the sub-dean of the Auckland Branch Faculty at which final-year students of University of Otago, School of Medicine, completed their training. In 1958, on the retirement of Sir Charles Hercus, Sayers was appointed as dean of the University of Otago, School of Medicine, together with a chair in therapeutics. His inaugural lecture was on malaria, which was also the subject of his MD thesis that he completed in 1959.
As dean of the medical school he was involved in the revision of the clinical content of fourth- and fifth-year teaching and new chairs in psychological medicine and paediatrics were established during his tenure. He was involved in persuading the Wellcome Trust to establish a research chair in medicine and the funding of a building for medical research.
Sayers served on committees of the Royal Australasian College of Physicians (RACP), and was the first New Zealander to serve as president of the RACP from 1956 to 1958. He chaired the New Zealand Medical Council (1956–64) and he also served as president of the New Zealand branch of the British Medical Association (1963–64). He was appointed the colonel commandant of the Royal New Zealand Army Medical Corps (1964–67).
His services were recognised by the award of various honours. In the 1956 Queen's Birthday Honours, he was appointed a Companion of the Order of St Michael and St George, for public services as a prominent physician. He was elected a Fellow of the Royal Society of New Zealand in 1961, and he was made a Knight Bachelor in the 1965 New Year Honours. Later that same year he was appointed a Knight of the Order of St John. In 1975 he was awarded an honorary DSc by the University of Otago. He was also an Honorary Fellow of the Royal College of Physicians of Edinburgh and an Honorary Fellow of the American College of Physicians.
He retired from the University of Otago in 1968, although he continued with a consulting practice and was the chairman of the medical research distribution committee lottery fund and of the scientific committee of the National Heart Foundation. He died on 12 May 1985 in Dunedin.


Pale cell acanthoma


Clinical Therapeutics

Clinical Therapeutics is a monthly peer-reviewed medical journal that was established in 1977 and is published by Elsevier. It is an official journal of the European Association for Clinical Pharmacology and Therapeutics. The journal covers all aspects of clinical pharmacology and therapeutics.
Abstracting and indexing.
The journal is abstracted and indexed in:
According to the "Journal Citation Reports", the journal has a 2016 impact factor of 2.947.


Mabel Hokin

Mabel Ruth Hokin was a biochemist who spent most of her professional career conducting fundamental research in the University of Wisconsin Medical School. She is most well known for the work she did early in her career, along with then-husband Lowell Hokin, in the study of stimulated phosphoinositide turnover in secretory tissues, a key component of transmembrane signaling and many other cell regulatory processes which became known as the 'PI Effect'.
Early life.
Mabel Ruth Neaverson was born to working-class parents in the Heeley district of Sheffield, England in early 1924. She had two younger sisters, Mary and Dorothy. Mabel took to academic pursuits at an early age, excelling in elementary and grammar school as well as at bible scholarship. She spent 1942 to 1943 working in the Women's Land Army, where, among other things, she helped administer a refugee camp for Czech Jews. (Mabel converted to Judaism ten years later.)
She also became interested in costume design and theater, where she met her first husband, actor and playwright Dennis Davison.
Mabel worked as a technician in the Medical Research Council Unit for Research in Cell Metabolism under Hans Krebs at the University of Sheffield from 1943 to 1946, and enrolled as a student in 1946, continuing to work for Krebs. Krebs recognized Mabel's scientific mind and talent in the laboratory, and urged her to pursue doctoral work, which she began in 1949 after receiving her Bachelor of Science Honors degree in Physiology. She did her graduate research under Quentin Gibson in the Physiology department. In a short time, Mabel met Krebs' graduate student Lowell Hokin, and the two began a romantic as well as professional relationship. Mabel received her Ph.D. in 1952.
Scientific career.
Mabel and Lowell Hokin conducted research in fundamental biochemistry together from their doctoral research days in Sheffield, to their work at McGill University in the 1950s, up to the mid-1960s at the University of Wisconsin. From the mid-1960s, Mabel worked in her own areas of research with a particular focus on neurochemistry after she received a primary appointment in the Department of Psychiatry along with a joint appointment in the Department of Physiological Chemistry in the University of Wisconsin Medical School.
Mabel and Lowell's most significant
work came very early in their careers, and was first published in their seminal 1953 paper
in the Journal of Biological Chemistry. In it, Mabel and Lowell described experiments in which they stimulated enzyme secretion in slices of pigeon pancreas in the presence of media containing the radioisotope P32. They found that the phospholipid fraction from the stimulated slices, formerly thought to contain fairly inert structural components of cell membranes, contained up to 9 times as much P32 as it did in the non-stimulated control samples. In a 1955 paper
Lowell and Mabel showed that the bulk of the P32 went into phosphatidate and 'a phosphoinositide' that was later identified as phosphatidylinositol (PtdIns). They then showed that this metabolic response, which became known as the 'PI effect', occurred in a variety of stimulated tissues, such as pigeon pancreas (1958),
suggesting that it plays a widespread role in cell regulation. Mabel and Lowell summarized their cell membrane biochemistry research in a 1965 article
in Scientific American. In 1974, Mabel provided some of the first experimental evidence that launched the modern phase of work in this area
(she published as M. Hokin-Neaverson after her 1971 divorce from Lowell).
In the 1970s, Mabel became interested in the biochemistry of the brain, or neurochemistry, and, as a full professor, led the Laboratory for Neurochemistry Research in the Department of Psychiatry in the University of Wisconsin Medical School, which was conveniently located in the same building as the physiological chemistry, pharmacology, and anatomy departments, where her colleagues worked and from which she drew graduate students. She delved into undergraduate teaching at one point, teaching a course on drugs and the mind in the early 1970s, but her primary teaching activity was guiding graduate students and teaching graduate biochemistry courses. Unlike her earlier research, which exclusively employed animal tissues, Mabel also studied blood samples from humans, including mentally ill patients, and contributed to the understanding of the biochemical basis of mental illness, showing the first biochemical marker for one of the major psychoses. Mabel's assistant, Ken Sadeghian, worked with her from the 1960s until her retirement.
Interest in the PI effect waned in the 1960s and 1970s, but experienced a resurgence in the 1980s due to advances in technology and understanding of cell membrane biochemistry. Mabel and Lowell became regarded as founders of an important and still growing field of biochemistry and cell biology — the many roles of inositol phospholipids in cell function — for which they were honored at a 1996 symposium at the University of Wisconsin that gathered their colleagues from around the world. Their early work was highlighted in a 20th anniversary review of the discovery of inositol-1,4,5-trisphosphate as a second messenger,
and their 1953 and 1958
JBC articles were celebrated as "JBC Classics" in 2005.
Personal life.
Most of Mabel's life was spent under a shadow cast by autoimmune illness. At the age of 16 she was diagnosed with lupus and given a dire prognosis for longevity. It turned out, however, to be a nonfatal autoimmune connective tissue disease with which Mabel struggled for the rest of her life. In the mid-1960s, treatment with steroids became established, and Mabel's steroid treatment led to degradation of her hip joints. She was an early recipient of artificial hips at Mayo Clinic in 1972.
Mabel and Lowell had hoped to move to the United States after finishing their doctoral work in Sheffield, but Mabel's earlier activities as chair of the Sheffield University Socialist Society and member, along with then-husband Dennis Davison, of the Communist Party of Great Britain, led to her being blacklisted from entry into the United States during the McCarthy Era. Instead, Mabel and Lowell obtained positions at the Montreal General Hospital Research Institute at McGill University in 1953. While conducting research at McGill they petitioned the United States government to allow Mabel entry into the U.S., but it was not until 1957 that they were able to move to their new jobs in Wisconsin. From their arrival in Montreal in 1953 to their departure in 1957, Mabel was unable to attend any research conferences in the United States.
Wisconsin was chosen for several reasons: Lowell received a junior faculty appointment in the Department of Physiological Chemistry, Mabel obtained a position in the department that allowed her to continue her research with Lowell, and Lowell's parents lived close by in Peoria, Illinois.
Mabel had three children. In 1966 the family moved to a home on Lake Mendota, where Mabel lived for the rest of her life.
Mabel and Lowell were divorced in 1971.
In 1986, Mabel and Bernard Biales, who had worked in her lab at one time, began a relationship that lasted until her death. They married in hospice on July 22, 2003.
Mabel Hokin died in Madison on August 17, 2003.


Melanie Melanson

Melanie Jo Melanson (born November 1, 1974) is a missing teenager from Woburn, Middlesex County, Massachusetts. She vanished while at a party on October 27, 1989; at first, investigators believed she fled to Florida. However, subsequent investigations by both authorities and a private investigator have turned up no leads.
Disappearance.
Melanson was a freshman in high school, and looking forward to a change of schools. At the time of her disappearance, she was living with her grandmother yet maintained contact with her parents. She was asked to attend a party on the evening of October 27, 1989.
On the day of her disappearance, Melanson and a friend left school early and decided to go home. That night, she told her grandmother she was going to have a sleepover at a friend's house (the friend was also her next-door neighbor). Melanson used the story to cover her attendance at the party. The party was held in a patch of woods near an industrial park; Melanson was the youngest guest there. She went with a group of five male friends. The party did not end until early the next morning; no one who knew Melanson saw or heard her returning from the party.
During the afternoon of October 28, after Melanie's family discovered she had been at the party, they frantically called almost every attendee they could reach. They learned nothing of Melanson's whereabouts. Finally, they reported her missing.
The police determined that she was last seen with two boys she had known. They gave conflicting stories of what might have happened to her. Police said each boy claimed the other was the last one who had been with Melanson. One of the boys also said he had seen her at the very head of a trail in the early morning hours of October 28.
Investigation.
The Woburn Police Department originally thought that Melanson had run off to Florida, as she had run away before. They organized a massive search to find the teenager, using everything from cadaver dogs to helicopters, and there were substantial digs as well. None of the searches were successful, and no clues to Melanson's disappearance were found. There have been no arrests in the case. In August 1992, an anonymous caller suggested police should search a pond near the party site; although police followed up, nothing was found.
Aftermath.
In the spring of 2009, authorities announced a renewed push on the case and offered a $5,000 reward for information to solve it. In 2012, a doctor hired in the case has used a new science method called Decomposition Odor Analysis (DOA) to help find Melanie.
Police now believe Melanson was a victim of foul play. Her grandmother and parents are now deceased.


Azygos

Azygos (impar), from the Greek άζυξ, refers to an anatomical structure that is unpaired. This is relatively unusual, as most elements of anatomy reflect bilateral symmetry. Azygos may refer to:


200 Cigarettes

200 Cigarettes is a 1999 American comedy film directed by Risa Bramon Garcia and written by Shana Larsen. The film follows multiple characters in New York City on New Year's Eve 1981. The film stars an ensemble cast consisting of Ben Affleck, Casey Affleck, Dave Chappelle, Guillermo Díaz, Angela Featherstone, Janeane Garofalo, Gaby Hoffmann, Kate Hudson, Courtney Love, Jay Mohr, Martha Plimpton, Christina Ricci and Paul Rudd. The film also features a cameo by Elvis Costello, as well as paintings by Sally Davies.
Plot.
The film follows various plot arcs all occurring on New Year's Eve of 1981. Monica (Martha Plimpton) is throwing a big New Year's bash and is desperately afraid no one will attend. Early on the only person to have arrived is her friend Hillary (Catherine Kellner). As she tries to convince Hillary to stay, various other groupings of individuals are shown making their way to the celebration.
The film follows several characters as they spend New Year's Eve in New York City before eventually showing up at Monica's party. The party guests are: Val (Christina Ricci) and Stephie (Gaby Hoffmann), teens from Ronkonkoma who get lost in the seedy Alphabet City section of the borough and wander into a punk club where they meet Dave (Guillermo Díaz) and Tom (Casey Affleck), who have a "package" they need to deliver; ditsy and awkward Cindy (Kate Hudson), who is on a dinner date with the paranoid Jack (Jay Mohr); Lucy (Courtney Love) and her best friend Kevin (Paul Rudd), who are struggling with the sexual tension between them; Kevin's feminist ex-girlfriend Ellie (Janeane Garofalo), who walks in on Kevin and Lucy making out in a restroom stall; a dim-witted and flirtatious bartender (Ben Affleck); competitive friends Bridget (Nicole Ari Parker) and Caitlyn (Angela Featherstone) who attempt to ditch Bridget's boyfriend Eric (Brian McCardie), (who is also Monica's ex-boyfriend); and the eccentric cab driver (Dave Chappelle) who takes them all around town throughout the evening in his disco-themed taxi.
Eventually, all the characters find their way to the party, although in the meantime Monica has passed out after drowning her sorrows in alcohol. She wakes up the next morning to find many unrecognizable people on her floor, including Stephie who tells her what a big hit her party was. Monica is thrilled, even though she missed it all, especially when she finds out that Elvis Costello showed up. The final montage shows Polaroids of the party, narrated by the disco cabbie, mostly featuring the unlikely romances from the party and the unconscious Monica being propped up by her party guests.
Release.
The film received generally negative reviews and grossed $6.8 million in the United States before video release.
On Rotten Tomatoes the film has an approval rating of 30% based on 63 reviews. On Metacritic the film has a score of 33% based on reviews from 26 critics, indicating "Generally unfavorable reviews",
Todd McCarthy of "Variety magazine" called the film "dismally unfunny" and questions "if any director could have surmounted the script’s limitations" and of the acting performances he says "only Garofalo and Ben Affleck manage to project any wit that cracks through the prevailing humorlessness."
Mick LaSalle of the "San Francisco Chronicle" gave it a positive review, saying "200 Cigarettes doesn't have a bad scene or a false note. The picture is a succession of pointed little moments, nicely written by Shana Larsen and acted with comic assurance and sensitivity."


Hidradenoma papilliferum


Death of Merit

The Death of Merit is a four-part documentary series, first three-parts are made by the Insight Foundation, a Dalit-Adivasi student group. It documents caste-based discrimination prevalent in the Indian higher education system that had resulted in a large number of suicides of Dalit students in Indian campuses.
These documentaries are based on the testimonies of parents and family members of students who committed suicide. They basically expose the kind of caste-based hostility and harassment Dalit and Adivasi students have had to suffer from the faculties, fellow students, and administration in some of the country’s premier educational institutions.
The first part in the series is titled The Death of Merit: A Documentary part 1, part 2. It was originally published on 24 April 2011 on the group's blog, at thedeathofmeritinindia.wordpress.com. This part documents testimonies of parents and family members of Dr. Balmukund Bharti, a final year MBBS student from All India Institute of Medical Sciences, New Delhi, who committed suicide on 3 March 2010.
The second part in the series titled Dr. Jaspreet Singh: The Death of Merit – Another Documentary documents the testimonies of parents and family members of Dr. Jaspreet Singh, a final year MBBS student from Government Medical College and Hospital, Chandigarh, who committed suicide on 27 January 2008.
The third in the series is titled The Death of Merit: Manish Kumar (IIT Roorkee) part 1, part 2 documents testimonies of parents and family members of Manish Kumar Guddolian, a second year student who was graduating from the Department of Computer Science & Information Technology, at Indian Institute of Technology (IIT) Roorkee, who committed suicide by jumping from the fifth floor of his hostel on 6 February 2011.
The fourth in the series is titled The Death of Merit: Dr. V. Ajay Sree Chandra [A Documentary Film] This documentary film is on Dr. Ajay Sree Chandra, an exceptionally studious scholar with an outstanding performance record. Born on 01 September 1985, Ajay took this extreme decision of taking his life as a last act of protest. On 27th August 2007, V. Ajay Sree Chandra hanged himself in one of the hostel rooms of the famed IISc, hostel room number F002 to be precise, leaving his father and two younger brothers behind. Yet another prey to the brahmanical devil which lurks around to kill anyone it finds. on 27 August 2007.
References


Basal cell papilloma


Dendrimer-encapsulated nanoparticles

Dendrimer-encapsulated nanoparticles (DENs) are nanoparticles ranging from 1.5 to 10 nm that are synthesized by a template approach using dendrimers. Monometallic, bimetallic and semiconductor nanoparticles have been synthesized using this method. The primary use for DEN's is as a catalyst due to their extremely high surface area to volume ratio. Advantages that DENs have over other nanoparticles is that they are monodisperse and easy to make.
Synthesis.
The first component in DEN synthesis is the dendrimer itself. By using different sizes, or generations, of dendrimers it is possible to control the size of the nanoparticle to be synthesized. Although there are many types of dendrimers, the most common is the poly(amidoamine) (PAMAM) dendrimer. These types of dendrimers are predominantly terminated with either amine or hydroxyl groups. The notation for these dendrimers are in the form of Gx-R, where x is generation of the dendrimer and R is the terminal group of the dendrimer (in most cases R= -OH or -NH2) When metal ions are introduced to a dendrimer in aqueous solution they form a complex with the tertiary amines of the dendrimer notated as Gx-R(Mp+)n, where Mp+ refers to the metal ions used and n refers to the average number of metal ions complexed within each dendrimer. After a complex has formed, a reducing agent such as sodium borohydride is introduced in a high molar excess and the metal ions are reduced to their zerovalent form and come together within the dendrimer to form the DEN notated as Gx-R(Mn) where M is the zerovalent metal used and n is the number of metal atoms.
Characterization.
DENs can be characterized mainly by ultraviolet–visible spectroscopy. The charge-transfer complex that forms between the metal ions and the dendrimer exhibits a ligand-to-metal charge transfer, or LMCT, band in the UV-Vis spectrum, indicating that a complex has formed. The specific wavelength of occurrence for these LMCT peaks are different for each metal.


List of neurochemists

This is a list of neurochemists.


Journal of Epidemiology

The Journal of Epidemiology is a Japanese peer-reviewed open access journal for epidemiological studies. It is the official journal published by the Japan Epidemiological Association. The editor-in-chief is Keitaro Matsuo (Aichi Cancer Center Research Institute). According to the "Journal Citation Reports", the journal has a 2019 impact factor of 3.691.


Pitch keratosis


Marcela Maus

Marcela V. Maus is an Associate Professor of Medicine at Harvard Medical School and Director of the Cellular Immunotherapy Program at Massachusetts General Hospital. She works on immunotherapy for the treatment of cancer, using genetically engineered T cells to target malignancies (cancer).
Early life and education.
Maus attended Stuyvesant High School in New York City. She was an undergraduate at Massachusetts Institute of Technology, where she majored in biology and literature. She earned her MD–PhD at the University of Pennsylvania, where she trained in the laboratory of Carl H. June, developing methods to expand T-cell populations, for medical therapies. She completed residency in Internal Medicine at the Hospital of the University of Pennsylvania from 2006 to 2008. She completed fellowship in Hematology and Oncology at the Memorial Sloan Kettering Cancer Center from 2008 to 2012.
Research and career.
In 2012 Maus returned to the University of Pennsylvania, where she became an assistant professor and director of translational medicine. Since 2015 Maus has worked in the Massachusetts General Hospital and Dana–Farber Cancer Institute. Here she leads the Cellular Immunotherapy Program which translates her research into clinical trials for patients with malignancies.
Maus develops chimeric antigen receptor (CAR)-T cells for cancer patients. She demonstrated that it is possible to use engineered CAR-T cells to identify and kill tumour cells that express a specific protein, EGFRvllI (variant III). She believes that using CAR-T cells in combination with checkpoint inhibitors used to treat other cancers. The cells can breakthrough the blood–brain barrier, infiltrate a tumour and illicit an immune response. Maus has used CRISPR-Cas9 to develop the CAR-T cells that incorporate a molecule called Bi-specific T-cell engager (BiTE). Bi-specific T cell engager continues to produce short-lived molecules that attack the tumour until it is destroyed. BiTEs contains two molecular arms, one which catches an antigen EGFR target on the tumour cells and the other locates a CD3 receptor of a nearby T cell. Once the target and T cell receptor are close to one another it can destroy the cancer cell. The BiTEs force the tumor and T cells together. Usually BiTE is too large to cross the blood-brain barrier, but as CAR-T cells can pass through, they can produce the BiTE inside the brain.
Maus is on the leadership team of "MicroMedicine", a start-up which creates automated microfluidics for targeted cell isolation from biological fluids"." Maus was awarded a Damon Runyon Cancer Research Foundation Stage 2 fellowship to develop CAR-T cells that can target abnormal antigens made from oncogenes. She has turned CAR-T cells into "armoured vehicles" which can target glioblastoma brain tumours.


Richard Ramchurn

Richard Ramchurn is a Scottish artist and film director. He directed, wrote and produced a pair of films with relatively new technology that allows audiences to portray films by control from the brain. This is done under his production and research company "AlbinoMosquito" that uses neuroscience through a NeuroSky headset to allow brain control over the movie. His films include "The Disadvantages of Time Travel" (2015) and "The Moment" (2018), along with credit from "The Sentinel".
He graduated in Illustration and Animation from Manchester Metropolitan University in 2000, and from 2002 began to work on art, eventually leading to visual skills in theatre and film that have been broadcast on BBC News along with being shown worldwide.


Deathloop

Deathloop is an upcoming action-adventure game developed by Arkane Studios and published by Bethesda Softworks. The game is to be released on September 14, 2021 for PlayStation 5 (under a one-year console exclusivity deal) and Windows.
Gameplay.
"Deathloop" has the player in the role of Colt, an assassin that is stuck in a time loop, waking up on a beach at the island of Blackreef. The other residents of Blackreef, a former army base where strange experiments had once been held, have invested in the island and have gathered for this night to hold a party that seemingly lasts forever, as at the end of each night, the island resets to the start of the party in that time loop. Because of this reset, the partygoers pay no heed to their actions or deeds since they wake up at the start of the loop with no memories or effects of the previous loop. While Colt is part of this loop, he retains memories from each loop, learning the behaviors and patterns of the partygoers with each loop.
Colt has been tasked to take out eight targets across the island before midnight, as leaving even one alive will cause the time loop to reset and undo his work. Further, should Colt die before taking out the eight targets, he will wake back up at the start of the loop. Unlike "", another game with a time loop that runs in real time and known to cause anxiety in players, the time loop in "Deathloop" is not strictly timed and is aimed to give players more time and freedom to take out these eight targets in one loop. The player uses a combination of stealth, parkour, and attack skills as in Arkane's previous "Dishonored" and "Prey" games to move about the game world, avoid or take out guards, and learn the patterns of Colt's targets to figure out the right order to eliminate these using guns, melee attacks, or other environmental means.
The game features a multiplayer aspect in which the player can alternatively take the role of Julianna, an agent tasked to protect the time loop and take out Colt. When the player takes this role, they will enter a random player's game and may interfere with their play. The multiplayer portion is optional and players can prevent others from taking on the role of Julianna in their game, instead leaving this to a computer-controlled opponent to try to stop Colt.
Development and release.
"Deathloop" is being developed primarily by Arkane Studios at their Lyon, France locations. Game director Dinga Bakaba described the game as an "inverted "Cluedo"", a murder puzzle that the player needs to figure out how to solve in one perfect run after failing through many previous runs. The game is designed around aiding the player in learning the necessary pieces to this puzzle with each run, but they needed an element of unpredictability to make it a challenge. While current artificial intelligence (AI) in video games can lead to believable behavior, AI tends to lack surprising actions. This led to bringing in second online player to control Julianne as to randomly affect the player's game, itself something Arkane had explored in their unreleased title "The Crossing".
"Deathloop" combines elements of both the "Dishonored" series as well as "Prey". They wanted to be able to give the player a wide range of abilities that they could select to try to complete the "perfect loop", many which mirror powers from both "Dishonored" and "Prey". While the game does allow the player to use stealth and related abilities as in "Dishonored" to move quietly, "Deathloop" does not allow for non-lethal takedowns of non-player characters, as Arkane recognized the choice of killing or subduing enemies had weighed down players in "Dishonored". These stealth abilities can still be chained together with other abilities to make Colt fight like John Wick, according to Bakaba. The Julianne character has a similar range of abilities, many of these closer to the "Prey" abilities such as being able to mimic any character in the game, including Colt, and thus interfere through activities such as drawing the player away from the real target with her mimicry or by posing as a duplicate Colt in front of one of the targets to cause confusion that way.
The game's setting of Blackreef is based on the Faroe Islands, and inspired by the styles of the Swinging Sixties.
"Deathloop" was revealed at E3 2019. It was further showcased during Sony's PlayStation 5 event in June 2020, confirming that the game will see release as a timed console exclusive on the PlayStation 5 in late 2020 alongside a Windows release. In August 2020, it was announced the game was delayed until Q2 2021 as development was impacted by the governmental response to the ongoing COVID-19 pandemic. The company later announced it planned to release "Deathloop" on May 21, 2021. About a month prior to the planned May release, Arkane delayed the release until September 14, 2021, stating that they will be "using this extra time to accomplish our goal: create a fun, stylish, and mind-bending player experience."
On September 21, 2020, Bethesda Softworks' parent company, ZeniMax Media and Microsoft announced Microsoft's intent to buy ZeniMax and its studios, including Arkane, for , incorporating the studios as part of Xbox Game Studios, with the sale finalized on March 9, 2021. Xbox Game Studios head Phil Spencer said that this deal will not affect "Deathloop"s current planned platform-exclusive released on the PlayStation 5, and will remain exclusive there for a year before arriving on other consoles.


William Frederick Steuart

William Frederick Steuart (1816–1889) was a Maryland-born medical doctor who served in the Confederate States Army during the American Civil War. He was a surgeon in the 3rd North Carolina Infantry Regiment, a unit that formed part of the brigade commanded by his cousin, General George H. Steuart. After the war he returned to Maryland and served as resident physician at the Maryland Hospital for the Insane, an institution founded largely thanks to the efforts of another cousin, Richard Sprigg Steuart.
Early life.
Steuart was born on January 1, 1816 in West River, Anne Arundel County, the son of Maryland physician Charles Calvert Steuart and his wife Anne Fitzhugh Biscoe. His grandfather was the Maryland physician Charles Mark Steuart (1750-1798) and his great-grandfather was the planter and politician George Hume Steuart (c1700-1784). On 27 February 1840 William Steuart married Anne Hall, the daughter of Henry Hall and Mary Stevenson, with whom he had a large family.
Civil War.
Like other members of the Steuart family, Steuart was sympathetic to the Southern cause. On the outbreak of war, he found himself obliged to flee his home state of Maryland, which remained in the Union, to join the rebellion. As a Confederate sympathiser he had been closely watched by the authorities in Maryland. One of his sons was arrested and imprisoned, and shot dead while attempting to escape, hardening Steuart's own views against the Union.
Steuart and his wife fled their home state and joined the Confederate cause with around $20,000 in paper and precious metal which they smuggled out of Maryland, rolling up bills of exchange and hiding them in their belongings. They promptly invested their small fortune in Confederate bonds, so certain were they of Southern success in the war.
Steuart served as a surgeon in the 3rd North Carolina Infantry Regiment, a unit that mustered at Garysburg, North Carolina, in May, 1861 and formed part of the brigade commanded by his cousin, General George Hume Steuart. His assistant surgeon was Thomas Fanning Wood, whose detailed account of the regiment's wartime experience would be published in 2000 by the University of Tennessee Press.
In 1862 his eldest son Captain Henry "Harry" August Steuart (1840-11 May 1862) was captured while running medical supplies to the Confederacy, and killed.
Despite being "esteemed by officers and men" in the regiment, it appears that army life was too much for him, as the "rigors of march" and the "hardships of camp" eventually obliged him to apply to be posted away from front line duty. This may have been due to his age; Steuart was around 50 years of age when he joined the Southern armies.
He was replaced by Dr B M Cromwell, formerly of the 1st North Carolina Infantry Regiment, whose first service was at the Battle of Payne's Farm.
After the War.
After the war, Steuart returned to Maryland and private practice, where he became resident physician at the Maryland Hospital for the Insane, a pioneering institution dedicated to the care of mental illness which had been founded largely thanks to the efforts of his cousin, Richard Sprigg Steuart.
William Steuart died on December 10, 1889 and was buried in Christ Church, Owensville, Anne Arundel County, Maryland.
Family.
Steuart and his wife Ann had eleven children:


Amar Prasad Ray

Amar Prasad Ray was an Indian physician and malariologist. Born in 1913, he specialized in community health and the management of Malaria epidemic in India. He was an elected fellow (1962) of the Indian National Science Academy and a recipient of the 1974 World Health Organization Governance Award. He was honoured by the Government of India in 1967, with the award of Padma Shri, the fourth highest Indian civilian award for his contributions to the society. He was married to Mrs Kalyani Ray and had three children namely Mr. Rabindranath Ray , Mrs Ella Sen and Mrs Usha Mehta.


Topterone

Topterone (, ) (developmental code name WIN-17665), also known as 17α-propyltestosterone (or simply propyltestosterone) or as 17α-propylandrost-4-en-17β-ol-3-one, is a steroidal antiandrogen that was first reported in 1978 and was developed for topical administration but, due to poor effectiveness, was never marketed.


Lercanidipine

Lercanidipine (trade name Zanidip, among others) is an antihypertensive (blood pressure lowering) drug. It belongs to the dihydropyridine class of calcium channel blockers, which work by relaxing and opening the blood vessels allowing the blood to circulate more freely around the body. This lowers the blood pressure and allows the heart to work more efficiently.
The drug acts more slowly than older dihydropyridines. It probably has fewer adverse effects, but a comparatively high potential for drug interactions.
It was patented in 1984 and approved for medical use in 1997.
Medical uses.
Lercanidipine is used for the treatment of essential hypertension (high blood pressure).
Contraindications.
Like other dihydropyridines, lercanidipine is contraindicated in unstable angina pectoris, uncontrolled cardiac failure, shortly after a myocardial infarction, and in patients with left ventricular outflow tract obstruction. It is also contraindicated during pregnancy and in women who may become pregnant, because data regarding safety for the unborn are lacking, as well as in patients with severe liver and renal impairment.
The drug must not be combined with strong inhibitors of the liver enzyme CYP3A4 or with the immunosuppressant drug ciclosporin.
Adverse effects.
Lercanidipine is generally well tolerated; no single adverse effect has been observed in more than 1% of patients treated with this drug. Typical side effects are similar to those of other drugs of this class and include headache, dizziness, tachycardia (fast heartbeat), palpitations, flush, and oedema. Hypersensitivity reactions occur in less than one patient in 10,000.
Oedemas are significantly less common under lercanidipine when compared to first-generation dihydropyridines such as nifedipine. For other side effects, data are inconclusive: A study comparing lercanidipine to first-generation drugs found no difference in the frequency of headache and flush, but switching from amlodipine, felodipine or nitrendipine (all at least second generation) to lercanidipine significantly decreased side effects in another study.
Overdose.
Overdosing of up to 80 times the usual therapeutic dose has been described. Expected symptoms include severe hypotension (low blood pressure) and reflex tachycardia. Bradycardia (slow heartbeat) can also occur due to blockage of calcium channels in the atrioventricular node of the heart. There is no treatment besides monitoring blood pressure and heart function. Dialysis is likely ineffective because most of the lercanidipine is bound to blood plasma proteins and lipid membranes of cells.
Interactions.
The substance is metabolised by the liver enzyme CYP3A4. In a study, the strong CYP3A4 inhibitor ketoconazole increased the maximal blood plasma concentrations of lercanidipine by a factor of eight, and the area under the curve by a factor of 15. In another study, ciclosporin increased lercanidipine plasma levels threefold when given at the same time. Other inhibitors of this enzyme, such as itraconazole, erythromycin, and grapefruit juice, are also expected to increase plasma concentrations and thus amplify the antihypertensive effect. Conversely, CYP3A4 inductors such as carbamazepine, rifampicin, and St John's wort probably lower plasma levels and effectiveness of lercanidipine. By comparison, amlodipine has a lower potential for CYP3A4 mediated interactions.
Lercanidipine increases plasma levels of ciclosporin and digoxin.
Pharmacology.
Mechanism of action.
Like other dihydropyridine class calcium channel blockers, lercanidipine blocks L-type calcium channels in the smooth muscle cells of blood vessels, relaxing them and thus lowering blood pressure. In contrast to the non-dihydropyridine calcium channel blockers verapamil and diltiazem, it does not significantly act on calcium channels in the atrioventricular node, and therefore does not decrease heart rate, in usual therapeutic doses.
Pharmacokinetics.
Lercanidipine is slowly but completely absorbed from the gut. It has a total bioavailability of 10% due to an extensive first-pass effect, or up to 40% if taken after a fatty meal. Highest blood plasma levels are reached after 1.5 to 3 hours. The substance is quickly distributed into the tissues and bound to lipid membranes, where it forms a depot. The circulating fraction is almost completely (>98%) bound to plasma proteins.
It is completely metabolized in the liver, mainly via CYP3A4. Elimination half-life is 8 to 10 hours, and the drug does not accumulate. Because of the depot effect, the antihypertensive action lasts for at least 24 hours. 50% are excreted via the urine.
Chemistry.
Lercanidipine is used in form of the hydrochloride, which is a slightly yellow crystalline powder and melts at in crystal form I or in crystal form II. It is readily soluble in chloroform and methanol, but practically insoluble in water. This high lipophilicity (compared to older dihydropyridines) is intentional because it causes the substance to bind to lipid membranes, allowing for a longer duration of action.
The lercanidipine molecule has one asymmetric carbon atom. While the "S"-enantiomer is more effective than the "R"-enantiomer, marketed formulations contain a 1:1 mixture of both (i.e., the racemate).
Detection in body fluids.
Blood plasma concentrations of lercanidipine can be detected by liquid chromatography–mass spectrometry methods.


Lenticular book

A Lenticular book is created with the help of lenticular printing technology. This special type of printing gives rise to books, the text is accompanied by pictures with 3D graphics. Pictures of lenticular book arouse the illusion of depth or transition depending on your perspective. Lenticular book is also called stereoscopy or 3D book. The first worldwide 3D lenticular printed book with the story is Lentibook Pirate Girl.
Lenticular printing technology.
Lenticular printing technology and stereoscopy is a complicated method of producing imagery that allows spatial visual perception. There are different types of lenticular printing, the technology has evolved from simpler to more complex methods. Initially, it was a combination of two alternating images. With this basic application lenticular printing can be found, for example, child rulers with varying images depending on the inclination of rulers and angle of view. Gradually the technology has been better and better and allows the creation of images with stereoscopic 3D effects that are used such as posters, billboards or postcards. This advanced technological process stereoscopic 3D effect is used in the production of lenticular book.
The current trend lenticular book.
Currently lenticular book develops as a modern version of the classic children's book, which offers a varied, entertaining and inspiring imagery that develops a child's imagination. With emerging technology is evolving quality lenticular images in the book, which are still better and more varied. This makes it possible to use 3D book seizure of the child, but also as a teaching tool that motivates and leads to reading and concentration.
Production of images with 3D effect.
Production of images with the 3D effect is very demanding in terms of complexity of technological processes and in terms of time and money. Print of image size 5.9 × 8.7 cm takes about three and a half minutes and the price varies between 119 and 298 CZK for one frame of this size. The whole production process involves a complex preparation of documents, which leads to animation files in special 3D programs, intensive preparation for printing and using powerful and expensive printers. Lenticular technology has considerable manufacturing tradition in the Czech Republic. The aforementioned lenticular book Lentibook Pirate Girl or if Pirátka Kačenka is also Czech product.


Dennis G. Peters

Dennis Gail Peters (April 17, 1937 – April 13, 2020) was an analytical chemist who specialized in electrochemistry and was named the Herman T. Briscoe Professor at Indiana University in 1975. Peters led his own research group at Indiana University in Bloomington, Indiana until his death in 2020. Peters' research focused on the electrochemical behavior of halogenated organic compounds, more recently moving to focus on transition metal catalysts in regards to the oxidation and reduction of organic species. He authored or co-authored over 210 publications and 5 analytical chemistry textbooks.
Early life and education.
Dennis Peters was born on April 17, 1937, in Los Angeles, California. He completed his Bachelor of Science in chemistry from the California Institute of Technology in 1958 and graduated cum laude before completing his PhD in analytical chemistry at Harvard University under James J. Lingane. After completing his PhD in 1962, Peters went to Indiana University in Bloomington, Indiana.
Career.
Peters served as the chemistry department's graduate student advisor from 1969 to 1971 where he recruited the department's largest incoming class. His research has focused on the mechanistic and synthetic properties of the oxidation and reduction of halogenated organic compounds and electrocatalysis in organic synthesis. Peters was still actively teaching up to the time he suffered a fall during spring break 2020 and was taken to a hospital.
Death.
Peters died of hospital-acquired coronavirus disease 2019 on 13 April 2020, four days before his 83rd birthday. He contracted the virus while in a Bloomington hospital recovering from a fall. Peters' name was included in the May 2020 "New York Times" tribute "U.S. Deaths Near 100,000, An Incalculable Loss" to the 100,000 Americans who lost their lives as a direct result of the pandemic. A reporter for the "Indiana Daily Student" wrote that "Peters had a roaring voice that filled lecture halls".


Software pipelining

In computer science, software pipelining is a technique used to optimize loops, in a manner that parallels hardware pipelining. Software pipelining is a type of out-of-order execution, except that the reordering is done by a compiler (or in the case of hand written assembly code, by the programmer) instead of the processor. Some computer architectures have explicit support for software pipelining, notably Intel's IA-64 architecture.
It is important to distinguish "software pipelining", which is a target code technique for overlapping loop iterations, from "modulo scheduling", the currently most effective known compiler technique for generating software pipelined loops.
Software pipelining has been known to assembly language programmers of machines with instruction-level parallelism since such architectures existed. Effective compiler generation of such code dates to the invention of modulo scheduling by Rau and Glaeser.
Lam showed that special hardware is unnecessary for effective modulo scheduling. Her technique, "modulo variable expansion" is widely used in practice.
Gao et al. formulated optimal software pipelining in integer linear programming, culminating in validation of advanced heuristics in an evaluation paper. This paper has a
good set of references on the topic.
Example.
Consider the following loop:
 for i = 1 to bignumber
 A(i)
 B(i)
 C(i)
 end
In this example, let codice_1, codice_2, codice_3 be instructions, each operating on data codice_4, that are dependent on each other. In other words, codice_1 must complete before codice_2 can start. For example, codice_7 could load data from memory into a register, codice_8 could perform some arithmetic operation on the data, and codice_9 could store the data back into memory. However, let there be no dependence between operations for different values of codice_4. In other words, codice_11 can begin before codice_12 finishes.
Without software pipelining, the operations execute in the following sequence:
 A(1) B(1) C(1) A(2) B(2) C(2) A(3) B(3) C(3) ...
Assume that each instruction takes 3 clock cycles to complete (ignore for the moment the cost of the looping control flow). Also assume (as is the case on most modern systems) that an instruction can be dispatched every cycle, as long as it has no dependencies on an instruction that is already executing. In the "unpipelined" case, each iteration thus takes 9 cycles to complete: 3 clock cycles for codice_12, 3 clock cycles for codice_14, and 3 clock cycles for codice_15.
Now consider the following sequence of instructions "with software pipelining":
 A(1) A(2) A(3) B(1) B(2) B(3) C(1) C(2) C(3) ...
It can be easily verified that an instruction can be dispatched "each" cycle, which means that the same 3 iterations can be executed in a total of 9 cycles, giving an average of 3 cycles per iteration.
Implementation.
Software pipelining is often used in combination with loop unrolling, and this combination of techniques is often a far better optimization than loop unrolling alone. In the example above, we could write the code as follows (assume for the moment that codice_16 is divisible by 3):
 for i = 1 to (bignumber - 2) step 3
 A(i)
 A(i+1)
 A(i+2)
 B(i)
 B(i+1)
 B(i+2)
 C(i)
 C(i+1)
 C(i+2)
 end
Of course, matters are complicated if (as is usually the case) we can't guarantee that the total number of iterations will be divisible by the number of iterations we unroll. See the article on loop unrolling for more on solutions to this problem, but note that software pipelining prevents the use of Duff's device.
In the general case, loop unrolling may not be the best way to implement software pipelining. Consider a loop containing instructions with a high latency. For example, the following code:
 for i = 1 to bignumber
 A(i) ; 3 cycle latency
 B(i) ; 3
 C(i) ; 12(perhaps a floating point operation)
 D(i) ; 3
 E(i) ; 3
 F(i) ; 3
 end
would require 12 iterations of the loop to be unrolled to avoid the bottleneck of instruction codice_9. This means that the code of the loop would increase by a factor of 12 (which not only affects memory usage, but can also affect cache performance, "see code bloat"). Even worse, the prologue (code before the loop for handling the case of codice_16 not divisible by 12) will likely be even larger than the code for the loop, and very probably inefficient because software pipelining cannot be used in this code (at least not without a significant amount of further code bloat). Furthermore, if codice_16 is expected to be moderate in size compared to the number of iterations unrolled (say 10-20), then the execution will spend most of its time in this inefficient prologue code, rendering the software pipelining optimization ineffectual.
By contrast, here is the software pipelining for our example (the "prologue" and "epilogue" will be explained later):
 prologue
 for i = 1 to (bignumber - 6)
 A(i+6)
 B(i+5)
 C(i+4)
 D(i+2) ; note that we skip i+3
 E(i+1)
 F(i)
 end
 epilogue
Before getting to the prologue and epilogue, which handle iterations at the beginning and end of the loop, let's verify that this code does the same thing as the original for iterations in the middle of the loop. Specifically, consider iteration 7 in the original loop. The first iteration of the pipelined loop will be the first iteration that includes an instruction from iteration 7 of the original loop. The sequence of instructions is:
However, unlike the original loop, the pipelined version avoids the bottleneck at instruction codice_9. Note that there are 12 instructions between codice_28 and the dependent instruction codice_29, which means that the latency cycles of instruction codice_28 are used for other instructions instead of being wasted.
The prologue and epilogue handle iterations at the beginning and end of the loop. Here is a possible prologue for our example above:
 ; loop prologue (arranged on lines for clarity)
 A(1)
 A(2), B(1)
 A(3), B(2), C(1)
 A(4), B(3), C(2) ; cannot start D(1) yet
 A(5), B(4), C(3), D(1)
 A(6), B(5), C(4), D(2), E(1)
Each line above corresponds to an iteration of the main pipelined loop, but without the instructions for iterations that have not yet begun. Similarly, the epilogue progressively removes instructions for iterations that have completed:
 ; loop epilogue (arranged on lines for clarity)
 B(bignumber), C(bignumber-1), D(bignumber-3), E(bignumber-4), F(bignumber-5)
 C(bignumber), D(bignumber-2), E(bignumber-3), F(bignumber-4)
 D(bignumber-1), E(bignumber-2), F(bignumber-3)
 D(bignumber), E(bignumber-1), F(bignumber-2)
 E(bignumber), F(bignumber-1)
 F(bignumber)
Difficulties of implementation.
The requirement of a prologue and epilogue is one of the major difficulties of implementing software pipelining. Note that the prologue in this example is 18 instructions, 3 times as large as the loop itself. The epilogue would also be 18 instructions. In other words, the prologue and epilogue together are "6 times as large as the loop itself". While still better than attempting loop unrolling for this example, software pipelining requires a trade-off between speed and memory usage. Keep in mind, also, that if the code bloat is too large, it will affect speed anyway via a decrease in cache performance.
A further difficulty is that on many architectures, most instructions use a register as an argument, and that the specific register to use must be hard-coded into the instruction. In other words, on many architectures, it is impossible to code such an instruction as "multiply the contents of register codice_31 and register codice_32 and put the result in register codice_33", where codice_31, codice_32, and codice_33 are numbers taken from other registers or memory. This has often been cited as a reason that software pipelining cannot be effectively implemented on conventional architectures.
In fact, Monica Lam presents an elegant solution to this problem in her thesis, "A Systolic Array Optimizing Compiler" (1989) (). She calls it "modulo variable expansion". The trick is to replicate the body of the loop after it has been scheduled, allowing different registers to be used for different values of the same variable when they have to be live at the same time. For the simplest possible example, let's suppose that codice_1 and codice_2 can be issued in parallel and that the latency of the former is 2 cycles. The pipelined body could then be:
 A(i+2); B(i)
Register allocation of this loop body runs into the problem that the result of codice_39 must stay live for two iterations. Using the same register for the result of codice_39 and the input of codice_2 will result in incorrect results.
However, if we replicate the scheduled loop body, the problem is solved:
 A(i+2); B(i)
 A(i+3); B(i+1)
Now a separate register can be allocated to the results of codice_39 and codice_43. To be more concrete:
 r1 = A(i+2); B(i) = r1
 r2 = A(i+3); B(i+1) = r2
 i = i + 2 // Just to be clear
On the assumption that each instruction bundle reads its input registers before writing its output registers, this code is correct. At the start of the replicated loop body, codice_44 holds the value of codice_39 from the previous replicated loop iteration. Since codice_4 has been incremented by 2 in the meantime, this is actually the value of codice_1 in this replicated loop iteration.
Of course, code replication increases code size and cache pressure just as the prologue and epilogue do. Nevertheless, for loops with large trip counts on architectures with enough instruction level parallelism, the technique easily performs well enough to be worth any increase in code size.
IA-64 implementation.
Intel's IA-64 architecture provides an example of an architecture designed with the difficulties of software pipelining in mind. Some of the architectural support for software pipelining includes:


Mexiletine

Mexiletine (INN) (sold under the brand names Mexitil and NaMuscla) is a medication used to treat abnormal heart rhythms, chronic pain, and some causes of muscle stiffness. Common side effects include abdominal pain, chest discomfort, drowsiness, headache, and nausea. It works as a non-selective voltage-gated sodium channel blocker and belongs to the Class IB group of anti-arrhythmic medications.
Medical uses.
Mexiletine has several uses including the treatment of abnormal heart rhythms or arrhythmias, chronic pain, and myotonia.
In general when treating arrhythmias, mexiletine is reserved for use in dangerous heart rhythm disturbances such as ventricular tachycardia. It is of particular use when treating arrhythmias caused by long QT syndrome. The LQT3 form of long QT syndrome is amenable to treatment with mexiletine as this form is caused by defective sodium channels that continue to release a sustained current rather than fully inactivating, however other forms of long QT syndrome can also be treated with this medication.
Mexiletine has been used to treat chronic pain and may also be used to treat muscle stiffness resulting from myotonic dystrophy (Steinert's disease) or nondystrophic myotonias such as myotonia congenita (Thomsen syndrome or Becker syndrome).
Adverse effects.
Common side effects of mexiletine include abdominal pain, chest discomfort, drowsiness, headache, nausea and skin reactions. Uncommon or rare side effects include seizures and liver dysfunction.
Pharmacology.
Mexiletine is an oral analogue of lidocaine. It is a class IB antiarrhythmic which prolongs the refractory period by delaying the recovery from inactivation of sodium channels responsible for phase 0 of the cardiac action potential. The drug has a bioavailability of 90%, and peak plasma concentrations are seen after 2–4 hours. The mean drug half-life is approximately 11 hours. Mexiletine is predominantly metabolised by the liver. The pharmacokinetics of mexiletine are preserved with even moderate to severe renal impairment, but dose adjustment may be required when creatinine clearance falls below 10 mL/minute.
Society and culture.
Mexiletine is available for human use in the US, and has been reintroduced in the UK as a licensed product, having previously only been available as a 'named patient' import. The drug is sold under the trade name Mexitil for use in arrhythmias and NaMuscla for use in myotonia.
Veterinary uses.
Mexiletine is available to veterinarians in the US for the treatment of heart disease in dogs and cats. It is commonly used for the treatment of arrhythmogenic right ventricular cardiomyopathy (ARVC) in Boxer dogs in combination with sotalol.


List of RAL colors

Below is a list of RAL Classic colours from the RAL colour standard. The visual samples are approximate and informative only.
RAL Classic.
Overview.
Below is a list of RAL Classic colours from the RAL colour standard. Alongside every colour, the corresponding values are given for:
The visual samples displayed on the screen are not binding because brightness and contrast may vary from screen to screen – and neither are the colours on a printout from a printer. For binding colour samples, always obtain an official RAL Colour fan deck.
RAL Design System+.
In the RAL Design System Plus, there are groups of colours every 10° of hue and additionally at 75°, 85° and 95°. Possible lightness values are 15% through 90% in steps of 5% for monochromatic shades of gray (i.e. C = 0%) and 20% through 90% in steps of 10% and additionally 85% and 93%. Chroma values are also mostly confined to steps of 10% or 5%, but with some exceptions, and the maximum value varies.


Dendritic filopodia

Dendritic filopodia are small, membranous protrusions found primarily on dendritic stretches of developing neurons. These structures may receive synaptic input, and can develop into dendritic spines. Dendritic filopodia are generally less-well studied than dendritic spines because their transient nature makes them difficult to detect with traditional microscopy techniques. Sample preparation can also destroy dendritic filopodia. However, it has been determined that filopodia on dendritic shafts are distinct from other types of filopodia (even those found in dendritic growth cones) and may react to stimuli in different ways.
Structure.
Dendritic filopodia are thin and hairlike. They are defined as having a length that is at least twice the width, and they do not display the bulbous head found on dendritic spines. Filopodia are devoid of most cellular organelles, and are composed primarily of actin cytoskeletal elements. Synaptic contacts may occur along the length of the filopodia, not only at the end.
Role in Synaptic Transmission.
Dendritic filopodia may be the site of synapses in certain regions of the nervous system. In some neuronal cell types, such as in rat retinal ganglion cells, dendritic spines are not present, suggesting that in these cases, synaptogenesis occurs primarily on dendritic shafts or on filopodia themselves. Filopodia may synapse with neighboring axons both along the length of the filopodium and at the tip. Synaptic activity on dendritic filopodia may alter their morphology, or induce their transformation into dendritic spines (see transformation into spines.)
Role in Development.
In the early stages of neural development, dendritic shafts are overwhelmingly populated by dendritic filopodia. Gradually, the number of filopodia begin to decline concordant with a rise in spine number. Eventually, spines become the dominant structure on dendritic shafts with only a few filopodia present. Filopodia seem to grow in response to localized pulses of glutamate, suggesting that they may play a role in directing dendritic branching.
Transformation into Spines.
Dendritic filopodia can be readily observed transforming into dendritic spines. It has been proposed that filopodia may represent the precursors to dendritic spines and that their transience and motility may allow for selection of synaptic partners. Selection of synaptic partners may be dependent on detected synaptic activity in the vicinity of the filopodium. Localized glutamate signaling in the area of dendritic filopodia causes an increase in filopodial length, whereas blocking glutamate receptors reduces numbers of dendritic filopodia. Therefore, dendritic filopodia may be used by post-synaptic cells to detect passing axons. After contact between dendritic filopodium and a neighboring axon has been established, the filopodium retracts and the head begins to swell, taking on a more spine-like morphology. At this stage, the synapse is considered to be matured, and is perceived as more stable.
Although dendritic filopodia have been observed becoming dendritic spines, the process through which this occurs is unknown. Studies have reported that filopodia may undergo more than one stage of development before becoming spines, and that clustering of certain proteins such as Drebrin may be used to identify the maturity of filopodia. Mature spines contain enrichments of PSD95 protein at their spine heads, and PSD95 is often used as an indicator of spine maturity. However, dendritic filopodia can take on spine-like morphologies even without post-synaptic density proteins, pointing to actin remodeling as the primary process responsible for the development of spines from filopodia. Cytoskeletal analyses of spines versus filopodia have found that a spine-like morphology is associated with higher numbers of branched actin filaments. Therefore, proteins that interact with the arp2/3 complex as well as F-actin are under investigation for involvement in this process. Because filopodia are also sensitive to local concentrations of glutamate, proteins that interact with NMDA receptors in dendritic filopodia are also candidates for regulation of this process.
Role in Synaptic Plasticity.
Studies have shown that on mature dendritic stretches, NMDAR-mediated synaptic activity can spur the outgrowth of new filopodia, which can later develop into mature spine synapses. This finding represents a possible role for dendritic filopodia in synaptic plasticity because filopodia may serve as precursors to mature synapses even in mature neurons.
Role in Disease.
Although dendritic filopodia do not play a clear role in any particular disease, abnormally high numbers of filopodia have been found in the brains of patients with Autism spectrum disorders. This high-filopodia, low-spine phenotype may be due to failure of the filopodia to mature properly into spines. Mutations in the gene "SHANK3" have been shown to elicit similar phenotypes to those seen in the brains of patients with these disorders.


3-APPA

3-Aminopropylphosphinic acid, also known in the literature as 3-APPA or CGP 27492, is a compound used in scientific research which acts as an agonist at the GABAB receptor. It is part of a class of phosphinic acid GABAB agonists, which also includes SKF-97,541. It has a binding affinity to the GABAB receptor of 8.30 pKi.


Cortical minicolumn

A cortical minicolumn is a vertical column through the cortical layers of the brain. Neurons within the microcolumn "receive common inputs, have common outputs, are interconnected, and may well constitute a fundamental computational unit of the cerebral cortex". Minicolumns comprise perhaps 80–120 neurons, except in the primate primary visual cortex (V1), where there are typically more than twice the number. There are about 2×108 minicolumns in humans. From calculations, the diameter of a minicolumn is about 28–40 μm. Minicolumns grow from progenitor cells within the embryo and contain neurons within multiple layers (2–6) of the cortex.
Many sources support the existence of minicolumns, especially Mountcastle, with strong evidence reviewed by Buxhoeveden and Casanova who conclude "... the minicolumn must be considered a strong model for cortical organization" and "[the minicolumn is] the most basic and consistent template by which the neocortex organizes its neurones, pathways, and intrinsic circuits".
Cortical minicolumns can also be called cortical microcolumns. Cells in 50 μm minicolumn all have the same receptive field; adjacent minicolumns may have different fields.
Although many studies have observed Neurons structured into cortical columns, it is still widely disputed as to whether they serve a purpose or are even the smallest functional unit of the cortex, or whether Neurons are simply packed in such a way purely for efficient space usage and that the columns otherwise have no other role in Brain function.
Number of neurons.
Estimates of number of neurons in a minicolumn range from 80–100 neurons.
Jones describes a variety of observations that may be interpreted as mini- or micro-columns and gives example numbers from 11 to 142 neurons per minicolumn.
Number of minicolumns.
Estimates of the number of neurons in cortex or in neocortex are on the order of 2×1010. Most (perhaps 90%) of cortical neurons are neocortical neurons.
Johansson and Lansner use an estimate of 2×1010 neurons in the neocortex and an estimate of 100 neurons per minicolumn, yielding an estimate of 2×108 minicolumns.
Sporns et al. give an estimate of 2×107 – 2×108 minicolumns with no derivation.
Size.
The minicolumn measures of the order of 40–50 μm in transverse diameter; 35–60 μm; 50 μm with 80 μm spacing, or 30 μm with 50 μm. Larger sizes may not be of human minicolumns, for example macaque monkey V1 minicolumns are 31 μm diameter, with 142 pyramidal cells — 1270 columns per mm2. Similarly, the cat V1 has much bigger minicolumns, ~56 μm.
The size can also be calculated from area considerations. If cortex (both hemispheres) is 1.27×1011 μm2 then if there are 2×108 minicolumns in the neocortex then each is 635 μm2, giving a diameter of 28 μm (if the cortex area were doubled to the commonly quoted value, this would rise to 40 μm). Johansson and Lansner do a similar calculation and arrive at 36 μm (p51, last para).
Downwards projecting axons in minicolumns are ≈10 μm in diameter, periodicity and density similar to those within the cortex, but not necessarily coincident.


Adaptive optimization

Adaptive optimization is a technique in computer science that performs dynamic recompilation of portions of a program based on the current execution profile. With a simple implementation, an adaptive optimizer may simply make a trade-off between just-in-time compilation and interpreting instructions. At another level, adaptive optimization may take advantage of local data conditions to optimize away branches and to use inline expansion to decrease the cost of procedure calls.
Consider a hypothetical banking application that handles transactions one after another. These transactions may be checks, deposits, and a large number of more obscure transactions. When the program executes, the actual data may consist of clearing tens of thousands of checks without processing a single deposit and without processing a single check with a fraudulent account number. An adaptive optimizer would compile assembly code to optimize for this common case. If the system then started processing tens of thousands of deposits instead, the adaptive optimizer would recompile the assembly code to optimize the new common case. This optimization may include inlining code.
Examples of adaptive optimization include HotSpot and HP's Dynamo system.
In some systems, notably the Java Virtual Machine, execution over a range of bytecode instructions can be provably reversed. This allows an adaptive optimizer to make risky assumptions about the code. In the above example, the optimizer may assume all transactions are checks and all account numbers are valid. When these assumptions prove incorrect, the adaptive optimizer can 'unwind' to a valid state and then interpret the byte code instructions correctly.


Termination analysis

In computer science, termination analysis is program analysis which attempts to determine whether the evaluation of a given program halts for "each" input. This means to determine whether the input program computes a "total" function.
It is closely related to the Halting problem, which is to determine whether a given program halts for a "given" input and which is undecidable. The termination analysis is even more difficult than the Halting problem: the termination analysis in the model of Turing machines as the model of programs implementing computable functions would have the goal of deciding whether a given Turing machine is a total Turing machine, and this problem is at level formula_1 of the arithmetical hierarchy and thus is strictly more difficult than the Halting problem.
Now as the question whether a computable function is total is not semi-decidable, each "sound" termination analyzer (i.e. an affirmative answer is never given for a non-terminating program) is "incomplete", i.e. must fail in determining termination for infinitely many terminating programs, either by running forever or halting with an indefinite answer.
Termination proof.
A "termination proof" is a type of mathematical proof that plays a critical role in formal verification because total correctness of an algorithm depends on termination.
A simple, general method for constructing termination proofs involves associating a measure with each step of an algorithm. The measure is taken from the domain of a well-founded relation, such as from the ordinal numbers. If the measure "decreases" according to the relation along every possible step of the algorithm, it must terminate, because there are no infinite descending chains with respect to a well-founded relation.
Some types of termination analysis can automatically generate or imply the existence of a termination proof.
Example.
An example of a programming language construct which may or may not terminate is a loop, as they can be run repeatedly. Loops implemented using a counter variable as typically found in data processing algorithms will usually terminate, demonstrated by the pseudocode example below:
 i := 0
 loop until i = SIZE_OF_DATA
 process_data(data[i])) // process the data chunk at position i
 i := i + 1 // move to the next chunk of data to be processed
If the value of "SIZE_OF_DATA" is non-negative, fixed and finite, the loop will eventually terminate, assuming "process_data" terminates too.
Some loops can be shown to always terminate or never terminate through human inspection. For example, the following loop will, in theory, never stop. However, it may halt when executed on a physical machine due to arithmetic overflow: either leading to an exception or causing the counter to wrap to a negative value and enabling the loop condition to be fulfilled.
 i := 1
 loop until i = 0
 i := i + 1
In termination analysis one may also try to determine the termination behaviour of some program depending on some unknown input. The following example illustrates this problem.
 i := 1
 loop until i = UNKNOWN
 i := i + 1
Here the loop condition is defined using some value UNKNOWN, where the value of UNKNOWN is not known (e.g. defined by the user's input when the program is executed). Here the termination analysis must take into account all possible values of UNKNOWN and find out that in the possible case of UNKNOWN = 0 (as in the original example) the termination cannot be shown.
There is, however, no general procedure for determining whether an expression involving looping instructions will halt, even when humans are tasked with the inspection. The theoretical reason for this is the undecidability of the Halting Problem: there cannot exist some algorithm which determines whether any given program stops after finitely many computation steps.
In practice one fails to show termination (or non-termination) because every algorithm works with a finite set of methods being able to extract relevant information out of a given program. A method might look at how variables change with respect to some loop condition (possibly showing termination for that loop), other methods might try to transform the program's calculation to some mathematical construct and work on that, possibly getting information about the termination behaviour out of some properties of this mathematical model. But because each method is only able to "see" some specific reasons for (non)termination, even through combination of such methods one cannot cover all possible reasons for (non)termination.
Recursive functions and loops are equivalent in expression; any expression involving loops can be written using recursion, and vice versa. Thus the termination of recursive expressions is also undecidable in general. Most recursive expressions found in common usage (i.e. not pathological) can be shown to terminate through various means, usually depending on the definition of the expression itself. As an example, the function argument in the recursive expression for the factorial function below will always decrease by 1; by the well-ordering property of natural numbers, the argument will eventually reach 1 and the recursion will terminate.
 function factorial (argument as natural number)
 if argument = 0 or argument = 1
 return 1
 otherwise
 return argument * factorial(argument - 1)
Dependent types.
Termination check is very important in dependently typed programming language and theorem proving systems like Coq and Agda. These systems use Curry-Howard isomorphism between programs and proofs. Proofs over inductively defined data types were traditionally described using induction principles. However, it was found later that describing a program via a recursively defined function with pattern matching is a more natural way of proving than using induction principles directly. Unfortunately, allowing non-terminating definitions leads to logical inconsistency in type theories. That's why Agda and Coq have termination checkers built-in.
Sized types.
One of the approaches to termination checking in dependently typed programming languages are sized types. The main idea is to annotate the types over which we can recurse with size annotations and allow recursive calls only on smaller arguments. Sized types are implemented in Agda as a syntactic extension.
Current research.
There are several research teams that work on new methods that can show (non)termination. Many researchers include these methods into programs that try to analyze the termination behavior automatically (so without human interaction). An ongoing aspect of research is to allow the existing methods to be used to analyze termination behavior of programs written in "real world" programming languages. For declarative languages like Haskell, Mercury and Prolog, many results exist (mainly because of the strong mathematical background of these languages). The research community also works on new methods to analyze termination behavior of programs written in imperative languages like C and Java.
Because of the undecidability of the Halting Problem research in this field cannot reach completeness. One can always think of new methods that find new (complicated) reasons for termination.
References.
Research papers on automated program termination analysis include:
System descriptions of automated termination analysis tools include:


GJB6

Gap junction beta-6 protein (GJB6), also known as connexin 30 (Cx30) — is a protein that in humans is encoded by the "GJB6" gene. Connexin 30 (Cx30) is one of several gap junction proteins expressed in the inner ear. Mutations in gap junction genes have been found to lead to both syndromic and nonsyndromic deafness. Mutations in this gene are associated with Clouston syndrome (i.e., hydrotic ectodermal dysplasia).
Function.
The connexin gene family codes for the protein subunits of gap junction channels that mediate direct diffusion of ions and metabolites between the cytoplasm of adjacent cells. Connexins span the plasma membrane 4 times, with amino- and carboxy-terminal regions facing the cytoplasm. Connexin genes are expressed in a cell type-specific manner with overlapping specificity. The gap junction channels have unique properties depending on the type of connexins constituting the channel.[supplied by OMIM]
Connexin 30 is prevalent in the two distinct gap junction systems found in the cochlea: the epithelial cell gap junction network, which couple non-sensory epithelial cells, and the connective tissue gap junction network, which couple connective tissue cells. Gap junctions serve the important purpose of recycling potassium ions that pass through hair cells during mechanotransduction back to the endolymph.
Connexin 30 has been found to be co-localized with connexin 26. Cx30 and Cx26 have also been found to form heteromeric and heterotypic channels. The biochemical properties and channel permeabilities of these more complex channels differ from homotypic Cx30 or Cx26 channels. Overexpression of Cx30 in Cx30 null mice restored Cx26 expression and normal gap junction channel functioning and calcium signaling, but it is described that Cx26 expression is altered in Cx30 null mice. The researchers hypothesized that co-regulation of Cx26 and Cx30 is dependent on phospholipase C signaling and the NF-κB pathway.
The cochlea contains two cell types, auditory hair cells for mechanotransduction and supporting cells. Gap junction channels are only found between cochlear supporting cells. While gap junctions in the inner ear are critically involved in potassium recycling to the endolymph, connexin expression in the supporting cells surrounding the organ of Corti have been found to support epithelial tissue lesion repair following loss of sensory hair cells. An experiment with Cx30 null mice found deficits in lesion closure and repair of the organ of Corti following hair cell loss, suggesting that Cx30 has a role in regulating lesion repair response.
Clinical significance.
Auditory.
Connexin 26 and connexin 30 are commonly accepted to be the predominant gap junction proteins in the cochlea. Genetic knockout experiments in mice has shown that knockout of either Cx26 or Cx30 produces deafness. However, recent research suggests that Cx30 knockout produces deafness due to subsequent downregulation of Cx26, and one mouse study found that a Cx30 mutation that preserves half of Cx26 expression found in normal Cx30 mice resulted in unimpaired hearing. The lessened severity of Cx30 knockout in comparison to Cx26 knockout is supported by a study examining the time course and patterns of hair cell degeneration in the cochlea. Cx26 null mice displayed more rapid and widespread cell death than Cx30 null mice. The percent hair cell loss was less widespread and frequent in the cochleas of Cx30 null mice.


Ray Deakin

Raymond John Deakin (19 June 1959 – 24 December 2008) was an English footballer, whose playing position was left-back. He had a 14-year career in the Football League with Everton, Port Vale, Bolton Wanderers, and Burnley. He captained Burnley at Wembley in the 1988 Football League Trophy Final.
Playing career.
Born in Liverpool, Deakin began his career at Everton, where he signed his first professional contract under Gordon Lee in 1977. However, he never made any appearances for the "Toffees" first team, and was released from Goodison Park in 1981. He then joined John McGrath's Port Vale, where he spent one season. He was initially a regular in the "Valiants" team, but lost his place in October 1981 and struggled to break back into first-team contention thereafter. He claimed seven goals (including five penalties) in 27 Fourth Division and FA Cup appearances, having scored his first goal in the Football League on 5 September 1981, in a 1–1 draw with Darlington at Feethams.
Deakin left Vale Park and joined Bolton Wanderers on a free transfer in May 1982. John McGovern's "Trotters" were relegated out of the Second Division in last place in 1982–83, though only three more points would have seen Bolton escape the drop at the expense of Grimsby Town. Wanderers finished tenth in the Third Division in 1983–84, before dropping to 17th place in 1984–85. He scored two goals in 105 league games during his three-season stay at Burnden Park.
Deakin signed for Martin Buchan's Burnley in 1985. He scored three goals in 52 games in 1985–86 and again played all 52 games in the 1986–87 campaign, as he remained in the starting eleven as the "Clarets" switched manager from Buchan to Tommy Cavanagh and then to Brian Miller. An ever-present during his first two seasons at the club, he was eventually given the captain's armband. In May 1987, he captained Burnley at the lowest point of their history, when the club almost dropped out of the Football League, and only survived on the last day of the season with a 2–1 victory over Orient at Turf Moor. He played 48 games in the 1987–88 season, and captained the club at Wembley in the 2–0 defeat to Wolverhampton Wanderers in the final of the Football League Trophy. However he featured just 16 times in the 1988–89 season, as he began to become afflicted by injury; during his downtime he began training to be a coach driver. He forced his way back into new manager Frank Casper's first team with 35 appearances in the 1989–90 campaign. He played 50 games as Burnley reached the play-offs in the 1990–91 season, where they were beaten by Torquay United at the semi-final stage. He then announced his retirement from professional football.
Death.
In 2008, Deakin was diagnosed with terminal brain cancer and died on Christmas Eve that year, at the age of 49.
Statistics.
Source: