Plexin-A4 is a protein that in humans is encoded by the PLXNA4 gene.

Function

Plexin A4 binds to neuropilin 1 (Nrp1) and neuropilin 2 (Nrp2) and transduces signals from Sema3A, Sema6A, and Sema6B. These Nrp-plexin and semaphorin complexes initiate cascades that regulate diverse processes such as axon pruning and repulsion, dendritic attraction and branching, regulation of cell migration, vascular remodeling, and growth cone collapse. Both upregulation and downregulation of Plexin A4 has been observed following neural injury suggesting a dynamic role for Sema3A and Plexin A4 in neural maintenance and regeneration. Additionally, Sema3A and therefore its receptor, Plexin A4, have been implicated as possible components of fast-fatigable muscle fiber denervation in ALS.

Structure

Plexin A4 has ~1890 amino acids that include a likely signal sequence, transmembrane domain, and 12 extracellular N-linked glycosylation sites. It also contains domains consistent with other class A plexins including a Sema domain, three "Met-related sequences"/cysteine clusters, three extracellular glycine-proline repeats, intracellular SP domains, and a putative intracellular tyrosine kinase phosphorylation site.

Tissue distribution

In the adult rat central nervous system (CNS), plexin A4 was present in neurons and fibers throughout the brain and spinal cord, including neocortex, hippocampus, lateral hypothalamus, red nucleus, facial nucleus, and the mesencephalic trigeminal nucleus. Fibers expressed Plexin A4 in the lateral septum, nucleus accumbens, several thalamic nuclei, substantia nigra pars reticulata, zona incerta, pontine reticular formation, as well as in several cranial nerve nuclei. Plexin A4 has been found in dorsal and, to a greater extent, ventral horns of the spinal cord. Both motor neurons and interneurons in the ventral horn express Plexin A4. Motor axons exiting via the ventral roots and the ascending and descending white matter tracts express Plexin A4. In dorsal root ganglia, Plexin A4 is expressed in the neuronal cell bodies as well as the central and peripheral processes of those cells.

References


Carboxy-terminal domain RNA polymerase II polypeptide A small phosphatase 1 is an enzyme that in humans is encoded by the CTDSP1 gene.

Interactions

CTDSP1 has been shown to interact with SNAI1.

References

Further reading

External links


The Milei (also: Milea or Pârâul Milei) is a left tributary of the river Bâsca in Romania. Its length is  and its basin size is .

References

Rivers of Romania
Rivers of Buzău County


Membrane-spanning 4-domains subfamily A member 7 is a protein that in humans is encoded by the MS4A7 gene.

This gene encodes a member of the membrane-spanning 4A gene family, members of which are characterized by common structural features and similar intron/exon splice boundaries and display unique expression patterns in hematopoietic cells and nonlymphoid tissues. This family member is associated with mature cellular function in the monocytic lineage, and it may be a component of a receptor complex involved in signal transduction. This gene is localized to 11q12, in a cluster of other family members. At least four alternatively spliced transcript variants encoding two distinct isoforms have been observed.

References

Further reading


Pedro Rubén Décima (born March 10, 1964) is an Argentine former professional boxer.

Amateur career
As an amateur Decima represented Argentina as a bantamweight at the 1984 Olympic Games. His results were:
1st round bye
Defeated Tshoza Mukuta (Zaire) 5-0
Defeated Çemal Öner (Turkey) 4-1
Lost to Dale Walters (Canada) 0-5

Professional career
Decima turned pro in 1984 and captured the WBC super bantamweight title with an upset TKO win over Paul Banke in 1990, a fight in which Banke was knocked down three times in the 4th round.  He lost the belt in his first defense to Kiyoshi Hatanaka in 1991 and retired in 1993.

At his age, he works as a public boxer trainer in Buenos Aires, Argentina.

Professional boxing record

See also
List of super-bantamweight boxing champions

External links

sports-reference

1964 births
Living people
Super-bantamweight boxers
World super-bantamweight boxing champions
World Boxing Council champions
Argentine male boxers
Olympic boxers for Argentina
Boxers at the 1984 Summer Olympics
Sportspeople from Tucumán Province


Transcription factor HIVEP3 is a protein that in humans is encoded by the HIVEP3 gene.

Function

Members of the ZAS family, such as ZAS3 (HIVEP3), are large proteins that contain a ZAS domain, a modular protein structure consisting of a pair of C2H2 zinc fingers with an acidic-rich region and a serine/threonine -rich sequence. These proteins bind specific DNA sequences, including the kappa-B motif (GGGACTTTCC), in the promoters and enhancer regions of several genes and viruses, including human immunodeficiency virus (HIV). ZAS genes span more than 150 kb and contain at least 10 exons, one of which is longer than 5.5 kb (Allen and Wu, 2004).[supplied by OMIM]

It regulates osteoblasts.

Interactions

HIVEP3 has been shown to interact with TRAF1 and TRAF2.

References

Further reading

External links

Transcription factors


Ubiquitin-like protein 5 is a protein that in humans is encoded by the UBL5 gene.

It has been shown that in C. elegans mitochondria treated to lower expression of certain electron transport chain proteins during the L3/L4 stage, its expression levels is higher leading to increased lifespans.

Ubiquitin-like proteins (UBLs) are thought to be reversible modulators of protein function rather than protein degraders like ubiquitin (MIM 191339).[supplied by OMIM]

References

Further reading

External links


Ouvrage Michelsberg, one of the Maginot Line fortifications, formed part of the Fortified Sector of Boulay as well as the fortified region of Metz. The ouvrage is located in Moselle (département) between the towns of Dalstein and d'Ebersviller, about 23 km from Thionville. It is located between gros ouvrage Mont des Welches and petit ouvrage Hobling, facing Germany. Michelsberg did not see significant action in the Battle of France until June 1940, when it was attacked from the rear by German forces that had bypassed the Maginot Line. It successfully resisted these attacks, but was compelled to surrender in accordance with the 25 June 1940 armistice. After the Second World War it was renovated as a Cold War fortification against a potential Soviet invasion, then abandoned.  It is now operated as a museum, and may be visited.

Design and construction
Michelsberg was approved for construction by the Commission d'Organisation des Régions Fortifiées (CORF), the Maginot Line's design and construction agency, in April 1930 and became operational by 1935, at a cost of 56 million francs. The contractor was Gianotti of Nice. Unlike virtually all other Maginot positions, the ouvrage does not have a drinking water well inside the position: the intended well was dry, forcing the ouvrage to rely on a well outside.

Description
Michelsberg is a gros ouvrage, arranged in a linear fashion along a central underground gallery connecting the single combined personnel/ammunition entry block to the rear with the combat blocks about  to the east. It lacks a central "M1" ammunition magazine. It does possess an electrified 60 cm internal rail network, used to move supplies and munitions within the ouvrage. The galleries are excavated at an average depth of up to .

Mixed entry: inclined plan, one automatic rifle cloche (GFM), three automatic rifle embrasures and one machine gun/47mm anti-tank gun embrasure (JM/AC47).
Block 1: Infantry block with one retractable machine gun turret, one GFM cloche and one machine gun cloche (JM).
Block 2: Infantry block with one machine gun/anti-tank gun embrasure (JM/AC47), machine gun embrasure (JM) and two GFM cloches.
Block 3: Artillery block with one retractable 81mm mortar turret and two GFM cloches.
Block 4 (unbuilt): Planned artillery block with an 81mm mortar turret.
Block 5: Artillery block with one 75mm gun turret and one GFM cloche.
Block 6: Artillery block with one 135mm gun turret, one GFM cloche, one grenade launcher cloche (LG), oneJM cloche  and one emergency exit cloche (unique in the Line).

Apart from the emergency egress cloche, Michelsberg also features a false turret.

Casemates and shelters
In addition to the connected combat blocks, a series of detached casemates and infantry shelters surround Michelsberg, including

 Abri de Bilmette: Surface infantry shelter (abri)  with two GFM cloches.
 Casemate de Huberbusch Nord: SIngle block with one JM/AC37 embrasure, one JM embrasure and one GFM cloche.
 Casemate de Huberbusch Sud: SIngle block with one JM/AC37 embrasure, one JM embrasure and two GFM cloches.

Manning
The manning of the ouvrage in June 1940 comprised 472 men and 19 officers of the 164th Fortress Infantry Regiment and the 153rd Position Artillery Regiment, commanded by Commandant Pelletier. The units were under the umbrella of the 42nd Fortress Corps of the 3rd Army, Army Group 2.

The Casernement de Férange provided peacetime above-ground barracks and support services to Michelsberg and other positions in the area.

History

See Fortified Sector of Boulay for a broader discussion of the Boulay sector of the Maginot Line.

1940
On 15 June the German 1st Army broke through the Line at the Saar and pushed west and east along the Line, enveloping the French armies, meeting forces of the German 16th Army that had gone around the Line in the west in May. On 15 June Michelsberg fired 753 75mm rounds against the Germans. Troops of the German 95th Infantry Division moved behind Michelsberg on 21 June, taking fire from blocks 3 and 6. The ouvrage repulsed a full German attack on 22 June 1940, with help from Mont des Welches and Hackenberg. German artillery hit Block 3's cloches and the façade of Block 2. Block 6 destroyed a German battery with artillery fire. Following the Second Armistice at Compiègne on 25 June, the Boulay sector's garrisons surrendered on 4 July 1940. In the following years under German occupation, Michelsberg was used as a bombproof factory.

1944
During the Lorraine Campaign only Hackenberg was occupied by the Germans; Michelsberg played no role in that campaign. German forces did attempt to blow up the position when they evacuated, detonating explosives in the main gallery.

Cold War
Following World War II, interest revived in the use of the Maginot Line to defend against a possible Soviet advance through southern Germany.  Funds were allocated for restoration of the gros ouvrages  Work was limited to restoration of systems and improvements to existing armament.  The renovations did not include the command post or the barracks.  By 1956, Michelsberg had been designated part of the Mòle de Boulay, a strongpoint in the northeastern defenses against Soviet attack. By the late 1950s interest in fixed fortifications was waning after  France developed a nuclear deterrent.  The money needed to maintain and upgrade the fortifications was diverted for the nuclear programs. Michelsberg was maintained for use by the Army until 1971 when it was placed in second-class reserve.

After being abandoned, the ouvrage was used between 1978 and 1988 for the cultivation of mushrooms. The ouvrage was damaged and vandalized during this time.  Renovations and repairs started in 1992 and are ongoing. Since 1993 it has been protected by a charitable organization that allows visits on Sundays between April and September, inclusive. The volunteers are also restoring the nearby Abri de Bilmette.

See also

 List of all works on Maginot Line
 Siegfried Line
 Atlantic Wall
 Czechoslovak border fortifications

Notes

References

Bibliography
Allcorn, William. The Maginot Line 1928-45. Oxford: Osprey Publishing, 2003.
Degon, André; Zylberyng, Didier, La Ligne Maginot: Guide des Forts à Visiter, Editions Ouest-France, 2014.
Kaufmann, J.E. and Kaufmann, H.W. Fortress France: The Maginot Line and French Defenses in World War II, Stackpole Books, 2006.
Kaufmann, J.E., Kaufmann, H.W., Jancovič-Potočnik, A. and Lang, P. The Maginot Line: History and Guide, Pen and Sword, 2011.
Mary, Jean-Yves; Hohnadel, Alain; Sicard, Jacques. Hommes et Ouvrages de la Ligne Maginot, Tome 1. Paris, Histoire & Collections, 2001.
Mary, Jean-Yves; Hohnadel, Alain; Sicard, Jacques. Hommes et Ouvrages de la Ligne Maginot, Tome 2. Paris, Histoire & Collections, 2003.
Mary, Jean-Yves; Hohnadel, Alain; Sicard, Jacques. Hommes et Ouvrages de la Ligne Maginot, Tome 3. Paris, Histoire & Collections, 2003.
Mary, Jean-Yves; Hohnadel, Alain; Sicard, Jacques. Hommes et Ouvrages de la Ligne Maginot, Tome 5. Paris, Histoire & Collections, 2009.

External links
 Association «AOM 22juin 1940»
 Fort du Michelsberg, at Chemins de mémoire
 Historical, Technical Details specially from the Ouvrage Michelsberg
  A22 - GO du Michelsberg
 Ouvrage du Michelsberg at wikimaginot.eu
 L'ouvrage du Michelsberg at alsacemaginot.com
 Ouvrage du Michelsberg at lignemaginot.com
 Michelsberg (gros ouvrage A22 du) at fortiff.be

MICH
Môle de Boulay
Maginot Line
World War II museums in France


Fred Simmons Keller (January 2, 1899February 2, 1996) was an American psychologist and a pioneer in experimental psychology.  He taught at Columbia University for 26 years and gave his name to the Keller Plan, also known as Personalized System of Instruction, an individually paced, mastery-oriented teaching method that has had a significant impact on college-level science education system.  He died at home, age 97, on February 2, 1996, in Chapel Hill, North Carolina.

Life
Keller was born on January 2, 1899, on a farm near Rural Grove, New York, in Montgomery County. He was the only child to Vrooming Barney Keller and Minnie Vanderveer Simmons. Due to instability in his childhood, he left school at an early age to pursue employment as a Western Union telegrapher in Saranac Lake, New York. He enlisted in the U.S. Army in 1918 during World War I and served in Camp Jackson, South Carolina, in addition to active duty overseas in France and Germany. While in France, he served in battle five times, and in Germany he participated in the Army of Occupation. Keller exited the military ranking as a sergeant in August 1919.

Keller attended Goddard Seminary, in which he received athletic scholarship in 1919. However, he was accepted to Tufts College in 1920 through a scholarship and decided to attend there. Keller was majoring in English literature. Originally Keller had left school due to discrepancies with his attendance. During his time off of at school, he read John Watson's Psychology from the Standpoint of a Behaviorist, in which he returned to Tufts with a focus in psychology a few years later. He earned a B.S. from Tufts College in 1926 and was awarded an academic position in which he was employed for, for two years. Keller attended Harvard University for graduate school following his bachelor's degree in addition to teaching at Tufts.

Additionally, he took part in a position at Harvard College as a laboratory assistant and a tutor. Keller received his master's degree in 1928 and left Harvard College in 1931. During his time in Harvard, Keller took classes under E.G. Boring, who was the peak of Keller's career. Also, Keller met fellow graduate and famous psychologist, B.F. Skinner, in which they roomed together and became long-life friends. He found a job at Colgate University during the Great Depression and remained there for seven years until 1938. Following Colgate University he was offered a position at Columbia University; he was named assistant professor in 1942, associate professor in 1946, and professor of psychology in 1950. He also served as chairman of the department from 1959 to 1962 and became professor emeritus of psychology in 1964, the same year he retired from the university. In 1963 Keller was invited to Brazil to São Paulo to incorporate his new psychology into their existing academics. Keller returned to the U.S. and was invited back to Brazil, this time to the University of Brazila, where he was instructed to continue the development of his new findings. Upon returning for good, Keller found employment at the Institute for Behavioral Research, as well as Western Michigan University, Texas Christian University, and Georgetown University. Keller spent his time as a visiting professor, adjunct professor, as well as the chair at the listed universities. He retired in May 1976 from Georgetown University.

Keller's students appreciated him as their instructor, as well as appreciated his frequent reinforcers of their behavior. His "theoretical commitment to the power of positive reinforcement… he delivered were never routine" but "mechanical repetitions of 'uhhunh' or 'good. It was seen as a possible plan to increase academic performance and often singled out his students to denote praise. He was recognized throughout his life and was liked by many. After his death, a memorial was held in San Francisco by the Association for Behavior Analysis, in which over two hundred people took part in. Keller was also recognized for his "effects of his lectures on one student's behavior ... efficacy of his teaching" and "graceful flow of sentence into paragraph".

Contributions to psychology
Inspired by B. F. Skinner, Keller proposed a reinforcement theory that applies to his teaching in addition to research. He and William N. Schoenfeld produced a textbook as well as an introductory laboratory course in psychology that related animal psychology with white rats as their subjects. The textbook was called "Principles of Psychology," published in 1950. The book emphasized scientific methods in the study of psychology such as escape, avoidance, conflict, cooperation, imitation, verbal behavior, thinking, and concept formation. In addition to providing a course that initiated the first use of experimental analysis of behavior during his time at Columbia University, Keller and Schoenfeld provided a more concise understanding for concepts that Skinner proposed in his The Behavior of Organisms. Concepts were written in a clearer way for students to understand and was more appropriate for an undergraduate beginners course. In the lab, students were able to test the methods they were learning of in their lecture classes for the first time. Among their experiments, the students observed the responses of white rats to stimuli and rewards and measured human learning by testing people's ability to remember the pathways of mazes and other sensory processes.

Keller and Skinner interacted frequently, and even collectively held the 1947 conference on the Experimental Analysis of Behavior. The audience consisted of students from both colleges of Skinner and Keller and the precursors to their new movement. With the aid of students, Skinner and Keller were able to formulate, at the conferences held up until 1950, the Journal of the Experimental Analysis of Behavior, the Journal of Applied Behavior Analysis, Division 25 of the APA, the Association for Behavior Analysis, The Behavior Analyst, Analysis of Verbal Behavior, the Cambridge Center for Behavioral Studies, Behavior and Social Issues, and Behavior and Philosophy.

Keller subsequently studied learning in addition to behavior. He was the first to administer Skinner's previous findings into real-world applications by the process of transcribing auditory signals of Morse code into English. The method he used was called code-voice, which resembled Skinner's programmed instruction, which was fancied by the US Army. Code-voice was used mostly in the Signal Corps, although it was also used in other divisions, and became one of the most used methods in radio-operator training. The new method "represented an early application of the laws of learning to practical human affairs and served as a model for the study of several other skills" and was awarded by President Truman a certificate of Merit in 1948.

He was a fellow of the American Psychological Association and a past president of the Eastern Psychological Association. He received the Distinguished Teaching Award from the American Psychological Foundation in 1970.

Brazil
Concluding his years at Columbia University, he was invited to the University of São Paulo by Fulbright–Hays, in which he attended as a visiting professor. He spent one year in Brazil during 1961, establishing his reinforcement theory into the psychological presence. Keller constructed multiple experimental instruments used to test reinforcement, such as living cages that were constructed from ordinary resources. He used hard-wire cloths, wooden frames, bent wire that acted as levers, pencils, watches, and cocktail stirrers. Keller initiated a new psychology in the city of Brazil and was recognized heavily for it. His influence at the university initiated multiple students to travel to the US to continue the work of Keller.

Several years after returning from Brazil he got an invitation to come back in 1963. He was asked to create a novel department, designed completely by him (carta branca), called "personalized system of instruction". He spent his time at the University of Brasilia developing his new psychological program, in which he was forced to depart from in 1964. He continued his work in the US on the PSI, also known as the Keller Plan, with several other theorists, and his work continued in Brazil by his students. His work was also translated into Portuguese.

Personalized System of Instruction (PSI)
Keller's  paper "Good-bye, teacher..." issued in Journal of Applied Behavior Analysis in 1968 introduced the concept of Personalized System of Instruction (PSI). This lead later to "Mastery learning"  plan.

When Keller returned to the US, he continued the work he had started in Brazil dealing with the personalized system of instruction. His work was developed in collaboration with J. G. Sherman at Arizona State University, where he remained for three years. During his time, J. G. Sherman and Keller advanced principles associated with the PSI. These included
"(1) The semester's work was divided into, let's say, twenty units, in a logical progression such as the necessary background for each unit, was contained in the units that went before. (2) Repeated tests were given, administered by student "proctors" selected from those who had been most successful during the previous semester, and each student would continue testing on a given unit of the material until he had demonstrated satisfactory proficiency. Erroneous answers could be discussed, or even debated with the student proctor until a clear understanding was achieved. (3) The criterion for moving on to the next unit was not a particular understanding, but 'mastery' of a given unit of material. Eventually, all students, if they persisted, were expected to turn in a performance. (4) Each student worked at his own pace".

Students were encouraged to master each concept before moving on to a subsequent concept. This allowed each student to work at their own pace without fear of falling behind.

Following Arizona State, Keller attended in 1967 the Institute for Behavioral Research located in Silver Spring, Maryland. During his attendance, he developed several additional concepts in regards to the PSI and published a well-known paper called "Good-bye Teacher…." where the concept of PSI was first presented. In 1970 he had received the Distinguished Teacher Award given to him by the APA, as well as the honorary Doctor of Science degree from Long Island University in addition to Colgate University in 1976. Additionally, he was given the Behavioral Scientist medal in 1973 from the Institute for Behavioral Research and the Doctor of Humane Letters degree in 1976.

References

See also
 Behavioral activation

1899 births
1996 deaths
20th-century American psychologists
Colgate University faculty
Columbia University faculty
Harvard Graduate School of Arts and Sciences alumni
Tufts University alumni
People from Chapel Hill, North Carolina
Fellows of the American Psychological Association
Behaviourist psychologists


Laotian Australians, also known as Lao Australians (), refers to Australians who have either migrated from Laos and/or have Lao ancestry. The first Lao people that came to live in Australia arrived through the Colombo Plan in the 1960s, which gave a number of Laotians the opportunity to live and study in Australia. The migration of the Lao commenced with the Indochinese refugee crisis in 1975 following communist regime takeovers. According to the 2016 Census, there are 10,402 Laos-born Australians with the majority residing in New South Wales.

Demographic
The Laos-born community in Australia comprises several ethnic groups including the native Lao, Chinese, Hmong and Vietnamese groups. According to the 2016 Australian Census, most Laotian-Australians are ethnically Lao (64.3%), followed by Chinese (15.1%), Hmong (7.6%), Vietnamese (5.4%) and 7.5% identified as Other Ancestry. Most Lao stated they spoke Lao at home, followed by English, Hmong and Mandarin. The history of Lao people in Australia is more recent compared to other migrant populations, with over 80 percent of Laos-born people arriving in Australia pre-2007 compared to 60 percent for the overall overseas-born population.

Geographically, most Laotian-Australians are concentrated in New South Wales (50.2%) and Victoria (21.4%), which can be attributed to historical establishment of migrant hostels in these areas that housed recently arrived migrants.

Historical population statistics

History in Australia

Pre-migration and White Australia policy
Following the establishment of the Commonwealth of Australia on 1 January 1901, one of the first pieces of legislation passed was the Immigration Restriction Act of 1901, infamously known as the ‘White Australia policy’. The law placed restrictions on non-European immigration and made it difficult for Asians in particular to migrate to Australia. The act required that all migrants pass a European language dictation test in order to stay in the country. Subsequently, most Asian migrants were unable to pass the test, as it was administered at the discretion of immigration officials. The intention of keeping Australia white was bolstered by Edmund Barton, the nation’s first prime minister, who said of the ‘Chinaman’:“I do not think either that the doctrine of the equality of man was really ever intended to include racial equality. There is no racial equality. There is basic inequality. These races are, in comparison with white races—I think no one wants convincing of this fact—unequal and inferior.”             At the time, the overwhelming majority (98%) of Australians were white. In 1958, the requirement to pass the dictation test was removed and in 1975, the Whitlam government effectively ended the White Australia policy by passing the Racial Discrimination act, thus creating a path for Asian migration to commence in the years following.

The Colombo Plan
The first instance of Lao people staying in Australia consisted primarily of students who arrived through the Colombo Plan. Approximately 150 people of Laos-descent resided in Australia pre-1975, and by the beginning of 1975 there were over 600 Indochinese students in the nation in total.

Mass migration of Indochinese refugees, 1970–80s
In 1975, the abolition of the Kingdom of Laos and subsequent establishment of a communist state led to a tenth of the Lao population fleeing the country. The Australian Government established the Humanitarian Program in 1977, as a response to the influx of Indochinese migrants seeking asylum in the country which allowed Lao refugees to settle in Australia

In mid-1976, there were over 400 Laos-born people in Australia, and by 1986 this figure expanded to over 7000. The Lao constituted a small portion of Indochinese refugees, compared to over 80,000 Vietnamese and 13,000 Cambodians who resettled in 1986. During this migration period, Lao people crossed the Lao-Thai border by boat or by swimming and settled in Thai refugee camps. Most Lao people who migrated by boat were accompanied by their spouses, relatives and/or friends, in contrast to the experiences of other Indochinese refugees who were often separated from their family and friends during their journey to the Thai refugee camps.

Experience in migrant centers, 1970–80s
Following mass migration in the mid-to-late 1970s, Lao people amongst other Indochinese refugees were initially housed in migrant hostels. Commonwealth Hostels Limited, a government-sponsored organisation, operated 25 hostels which, in addition to accommodation, provided English-language courses, healthcare, catering and welfare services to new migrants. Several hostels in New South Wales were located in Cabramatta, Westbridge and East Hills, which has influenced the establishment of Indochinese enclaves near these areas and the broader Fairfield Local Government Area (LGA) in the present 2010s. In Victoria, there were migrant centers in Broadmeadows, Nunawading and Preston, and in South Australia, there was a hostel in Glenelg and Smithfield.

Initial stays in these migrant centers were short-lived with many Lao people leaving due to dissatisfaction with the food (22.6%) and a desire to move in with relatives and close friends in the community (54.8%). A quarter of Lao migrants left the centers in less than a month, and a further 39 percent left within 1–3 months. However, Lao people still perceived some benefits from their stay in the centers, including the ability to have paperwork processed which would allow them to integrate into Australian society (33.9%) and access to English-language classes (9.7%).

Lao people and other Indochinese ethnic groups chose to form enclaves in the Fairfield LGA nearby the migrant centers to be close to their relatives and friends. This allowed Lao people with low English proficiency levels to comfortably go about daily life without the obstacle of a language barrier impeding them. Other factors influencing the Lao people’s decisions to settle in Fairfield LGA included the affordability of housing and proximity to their children’s schools. For Lao people who chose to live in the Western suburbs outside of the Fairfeld Municipality, the dominant factor influencing this decision was a desire to be closer to their job.

Settlement of Lao people in Australia, 1990s
In the 1990s, the process of becoming an Australian citizen was less stringent compared to other countries which motivated Lao people to take up citizenship. In the US, the naturalization process required at least five years of permanent residence in the country, whereas the Citizenship Act in Australia allowed immigrants to become citizens with only two years of residence in the country provided they had basic English proficiency skills. In 1984, the act was amended to provide exemption to individuals over 50 applying for citizenship, recognizing the difficulty for older individuals in learning English. The majority of Lao people who settled in Australia attained citizenship within their first three years in the country. More than three quarters of Lao refugees became Australian citizens from 1975 to the 1990s, compared to 65 percent of Cambodians and 63 percent of Vietnamese refugees.

Impact of settlement on Lao family structure
Relations between Lao women and their spouses were markedly impacted upon migration to Australia, with 95 percent of Lao refugees stating their relationship with their husband or wife had changed since coming to Australia. Many women who were designated housewives in Laos had to join the Australian workforce as relying on a single source of income from the husband was insufficient for the cost of living in Australia. Gender dynamics shifted to more evenly distribute household labour amongst men and women - Lao women stated that their husbands had taken up more household duties in comparison to back home in Lao where typically the patriarch of the household would finish work and spend the rest of their leisurely time drinking with friends. However, a challenge faced by some Lao women was the threat of domestic violence, which made recently arrived migrants particularly vulnerable due to their lack of support system. Back in Lao, violence in the home was typically prevented or minimised through intervention by family and friends, however in Australia, this was not an option for some Lao women. Factors contributing to the propensity for Lao men to become violent upon migration to Australia included stress and trauma from the migration experience and financial-related pressures.

Employment in Australia
In the 1970s, a third of Lao people secured employment through connections with friends and relatives, with many jobs concentrating in the manufacturing industry. A smaller proportion (28.2%) of Lao-Australians stated they utilized resources provided by migrant centers to secure jobs including the assistance of Employment Officers. For unemployed Lao people looking for work, low levels of English proficiency (85.7%) were the dominant obstacle that preventing them from finding employment followed by a lack of job vacancies (42.9%). During the 1990s, Lao women typically worked in factories along with Lao men, although some men worked as janitors, gardeners or in construction.

Educational experiences
Many Lao children faced language barriers in educational settings and reportedly took twice as long to complete homework compared to Australian children. Despite these challenges, Lao children rapidly integrated into Australian society and began to adopt Western values over Lao traditions. Lao children became less likely to wholly obey their parent's wishes as was tradition in Laos. The assimilation of Lao youth into Australian culture was named a source of conflict with their parents, who expressed concern with their children dating and attending school functions and parties as was commonplace in Australia.

Cultural differences
In Australia, birthdays are often celebrated by Lao people as is commonplace in Western tradition, however this practice is less frequent in Lao. Traditionally, Lao culture is not as patriarchal as other Asian cultures, although women are still expected to be subservient and docile.  Many Lao women are afforded some independence and even more so for Lao-Australian women. For example, most women in Lao would take on their spouse’s last name however in Australia many women do not follow this tradition and instead choose to keep their own family name. Another tradition followed by women in Lao that is seldom practiced in Australia includes going to sleep after her spouse. However, other practices indicating the subservience of Lao women to men include washing her husband’s laundry separately to her own, which was still followed by some women in a 1990 study.

In Lao culture, respect for one's elders is a dominant value as influenced by Confucianism, and deems that younger people or individuals deemed of lower status, show deference to their elder/superior. Lao men and women use formal speech to address their elders in a manner which if translated to English would come off artificial. Conversely, Lao people in Australia may not be used to including polite phrases like 'Please' and 'Thank you' when speaking English as such terms are not commonly used in the Lao language.

Organisations
Organisations established by Laotians in Australia include the Lao Studies Society, the Council of Overseas Lao, the Lao Patthin Association, LaoAus Care Inc. and the Lao Women's Association. The leadership of these organisations is largely drawn from among the civil servants of the pre-communist government of Laos, as well as the international students who were sponsored to come to Australia under the Colombo Plan during that government.

Other organisations include the Lao-Australian Welfare Association based in Forest Hill, VIC and the Lao Australian Society which advocates for the development of Lao culture in the country. Additionally, the Laotian Language Program operated by SBS Radio caters to the Lao community and is run on Mondays from 4-5pm and Saturdays at 9-10pm.

Religion

Most Laotians (over 70%) in Australia are Theravada Buddhists, with a minority of Catholics. There are several main temples frequented by the Lao in Australia, including Wat Phrayortkeo Dhammayanaram located in Edensor Park, NSW and Wat Buddhalavarn in Wedderburn, NSW. In Victoria, major Lao temples include the Lao Buddhist Temple of Victoria, also known as Wat Dhammanivesaya.

Buddhist temples serve not only as a religious structure but also a community meeting place for Lao-Australians. Major festivals in Lao culture are held at major Buddhist temples including the Lao New Year (also known as Pi Mai or  Songkran) celebrations which takes place in mid-April. Water-throwing is a dominant activity during the festivities and is a means of wishing good fortune on others.

See also

 Asian Australians

Notes

References

Further reading

External links
  [CC-By-SA] (Lao in Sydney)


Single Ig IL-1-related receptor (SIGIRR), also called Toll/Interleukin-1 receptor 8 (TIR8) or Interleukin-1 receptor 8 (IL-1R8), is transmembrane protein encoded by gene SIGIRR, which modulate inflammation, immune response, and tumorigenesis of colonic epithelial cells.

Gene
Human gene SIGIRR is localized on chromosome 11. It is composed of 10 exons spanning about 11 700 base pairs. In mouse, this gene is on chromosome 7, where it is composed of 9 exons spanning about 9 400 base pairs.

Structure
SIGIRR is 410 amino acids long protein. In contrast with other members of IL-1 receptor family it has got only 1 immunoglobulin (Ig) domain in its N terminal extracellular part instead of 3 Ig domains. After this domain, there is a transmembrane domain, which is anchored to the plasmatic membrane. It has got TIR domain and 95 amino acids long C terminal tail in the intracellular part, which is not present in other  IL-1 receptor family members. Structure of the TIR domain is different in the case of SIGIRR. In its tertiary structure SIGIRR lacks amino acids Ser447 and Tyr536, which are important for IL-1R1 signalization. Instead of these amino acids SIGIRR contains Cys222 and Leu305. The functional importance of these differences is not known so far. Human and mouse SIGIRR protein sequences are 82%, identical and they are overall 23% identical with IL-1R1. SIGIRR is extensively glycosylated on its extracellular domain, and loss of this modification impairs its function.

Expression
SIGIRR is expressed in several epithelial tissues, particularly in epithelial cells of kidneys, digestive tract, liver, lungs, and in lymphoid organs. It is also expressed in monocytes, B lymphocytes, T lymphocytes, dendritic cells, and NK cells. In general, its expression is downregulated during inflammation or infection. Its reduced expression was also found in patients with chronic lymphoid leukemia, or in cells from colonic cancer. In human cells from colonic cancer, there was observed an increased expression of one variant of SIGIRR. This variant lacks its exon 8, is not glycosylated and its function is impaired. It also inhibits glycosylation of Wild type variant a its transport to plasmatic membrane.

One of the discovered transcription factor, which regulates the expression of SIGIRR, is SP1. It binds to the proximal part of the promoter of the SIGIRR gene and induce its transcription. Binding of SP1 on SIGIRR promoter is inhibited by the activation of p38 MAP kinase, which is activated through the TLR4 signalization. Treatment of mice with a small amount of lipopolysaccharide, which is a ligand of TLR4, causes reduction in SIGIRR expression.

Function
SIGIRR negatively regulates the activation of the IL-1R1, IL18R1, IL-1R5/ST2, TLR4, TLR7, TLR3, TLR9, and TLR1/2 and inhibits activation of transcription factor NF-κB and JNK MAP kinase.

SIGIRR interacts with IL-1R1 when it binds IL-1. N terminal extracellular immunoglobulin domain associates with IL-1R1 and blocks its heterodimerization with IL-1RAP. In addition, C terminal TIR domain of SIGIRR binds downstream elements of IL-1R1 signalization and prevents the constitution of the functional signalling complex. Deletion of these domains disrupts the regulation activity of SIGIRR. SIGIRR uses a slightly different mechanism to regulate the activity of TLR4. It also binds to receptor complex around TLR4. TIR domain of SIGIRR is crucial for interaction with TLR4, and it also interacts with downstream elements of the TLR4 pathway. In contrast, the extracellular immunoglobulin domain of SIGIRR is dispensable for the inhibition of TLR4 signalling. There are 2 mechanisms, which are proposed for explanation of this inhibition of the TLR4 pathway. First is that SIGIRR blocks the formation of signalling complex at activated TLR4 and the second is that SIGIRR prevents translocation of this signalization complex into a cytosol. SIGIRR inhibits signal transduction by its interaction with TLRs, IL-1R1 and downstream signalling proteins, and in this manner, it participates in negative regulation of inflammation. SIGIRR also prevents homodimerization of MYD88, and it also prevents signalization through adaptor protein TRIF, which is used, for example, by TLR3.

Negative regulation of IL-1R pathway by SIGIRR has its effect on the differentiation of Th17 lymphocytes. IL-1 supports differentiation for Th17 lymphocytes and expression of transcription factors RORγt and IRF4. Treatment by this cytokine also activates mTOR kinase and promotes the proliferation of Th17 lymphocytes. SIGIRR-deficient T lymphocytes lack this negative regulation, and it favours mTOR-dependent differentiation and proliferation of Th17 lymphocytes. SIGIRR also negatively regulates TLRs, IL-1R pathway, and following mTOR activation in intestinal epithelial cells. Ligands for TLRs in the intestine are mainly components of intestinal microflora. Its deficiency or expression of mutated form in these cells leads to the signalization, which promotes inflammation, proliferation and increases incidence of tumors and its size.

SIGIRR as a coreceptor of IL-1R5 for IL-37 binding
SIGIRR takes part in mediating the anti-inflammatory IL-37 signalization. It interacts with IL-37, IL-18R1 and forms tripartite signaling complex. Activity of this complex transduce anti-inflammatory signal and is essential for manifestation of IL-37 activity. Upon this signalization it causes inhibition of components of NF-κB pathway, kinases mTOR, TAK1, FYN, p38, JNK, ERK and it also causes activation of phosphatase PTEN, kinase MER, transcription factor STAT3 and adaptor protein p62 (DOK1). Pre-treatment of mice by IL-37 before injection of lipopolysaccharide reduced examined levels of pro-inflammatory cytokines and, also reduced their weight loss and hypothermia. This protective effect of IL-37 was abolished by deletion of SIGIRR, reduction of its expression or neutralization of IL-37 by antibodies.

In addition to the regulation of inflammation, IL-37 also affects metabolism. Stimulation of skeletal muscle cells by IL-37 increases level of AMP-dependent kinase, increases its activation and induces metabolic reprogramming. It causes increase of oxidative phosphorylation, Krebs cycle, nucleotide and amino acids metabolism, and decrease of inflammatory mediators levels. This response does not occur in case of SIGIRR deficiency

References

Further reading


Arginine vasopressin-induced protein 1 is a protein that in humans is encoded by the AVPI1 gene.

References

External links

Further reading


FK506-binding protein 10 is a protein that in humans is encoded by the FKBP10 gene.

The protein encoded by this gene belongs to the FKBP-type peptidyl-prolyl cis/trans isomerase family. It is located in endoplasmic reticulum and acts as molecular chaperones. Two alternatively spliced variants, which encode different isoform, are reported.

References

Further reading

EC 5.2.1
EF-hand-containing proteins


Jeff Lenosky (Born April 19, 1971) is an American world class professional Freeride and Trials Mountain Bicycle Rider.

Career
Among his many athletic high points is the world record for the Bunny hop, a high jump event using a full size mountain bicycle. Lenosky competes in events world wide and performs demonstrations of his athletic riding skills along with products manufactured by his many sponsors. He has a signature frame and pedals developed with his design input. Mountain bike events world wide have been designed and constructed with his planning, design, and organizational skills. A review of mountain biking periodicals will reveal regular featured columns written by Lenosky featuring, how to, adventures, motivational and news to the novice and experienced enthusiast. Many DVD and VHS films are on the market from locations worldwide along with his many friends included in the screenplays. Lenosky rides for Shimano (Saint), REEB, and Pearl Izumi. He also rides for Vittoria, Oskar Blues and Orange Seal.

Personal information
He lives in Sparta Township, New Jersey with his wife Amy and their children, Jack, Katie and Max. He is a graduate of East Stroudsburg University of Pennsylvania.

References

1971 births
Living people
American male cyclists
East Stroudsburg University of Pennsylvania alumni
Mountain bike trials riders
Freeride mountain bikers
People from Sparta, New Jersey
Sportspeople from Sussex County, New Jersey
American mountain bikers


The Taxation of Colonies Act 1778 was an Act of the Parliament of Great Britain that declared Parliament would not impose any duty, tax, or assessment for the raising of revenue in any of the colonies of British America or the British West Indies. The Act, passed during the American Revolutionary War, was an attempt by Parliament to end the war by conceding one of the early points of dispute.

Parliament's effort to tax the colonies without the consent of the colonists, especially as enacted in the Townshend Acts of 1767 and the Tea Act of 1773, had been a major cause of the American Revolution. This act noted that those taxes had "been found by experience to occasion great uneasiness and disorders" and that his Majesty desired "to restore the peace and welfare of all his Majesty's Dominions".

The Act declared that Parliament would not impose any duty, tax, or assessment for the raising of revenue in any of the colonies. Parliament would only impose such duties as expedient to regulate commerce and the net income from these duties would be given to the colonies. In making this concession, Parliament was taking the position that American colonists had advocated a decade earlier, most notably John Dickinson in his 1767 and 1768 "Letters from a Farmer in Pennsylvania".

By the time the statute was enacted, it was too late to have any effect on the war: the dispute was no longer specifically about taxation, and the colonies had already declared independence. Additionally, according to legal historian John Phillip Reid, "As a matter of constitutional law the statute was meaningless", because future parliaments would not be bound by the current parliament's pledge not to impose taxes.

The Act was eventually repealed by the Statute Law (Repeals) Act 1973 as obsolete.

References

Great Britain Acts of Parliament 1778
British laws relating to the American Revolution
Tax legislation in the United Kingdom
Repealed Great Britain Acts of Parliament


Javier Cambre -born Xavier Cambre in San Juan, Puerto Rico,  is a contemporary artist with dual citizenships from Spain and the US,  working in diverse media such as drawing, photography, collage, painting, text and sculpture. His maternal grandfather was the poet Evaristo Ribera Chevremont.

After earning with High Honors an Associate Degree in Engineering, Cambre studied architecture at Universidad de Puerto Rico (B. Arch. Design, Magna Cum Laude), Columbia University and at Universidad Pontificia Bolivariana (Dipl. Arquitecto) in Colombia. In 1998 Cambre graduated from the School of the Art Institute of Chicago with a Master of Fine Arts and was awarded a fellowship at the Whitney Independent Study Program, which he decided not to pursue after moving to NYC and spending two weeks in the program. Nevertheless, 4 years later he was selected to exhibit his work in the 2002 Whitney Biennial. Cambre is  a tenured professor in the Art and Design department at Queensborough Community College, City University of New York, where he has taught since the year 2000.

Cambre has exhibited his work at the 2002 Whitney Biennial, MoMA-P.S. 1 Contemporary Art Center, the Brooklyn Museum, the Sculpture Center, the Center for Curatorial Studies at Bard College, El Museo del Barrio and the Moore Space in Miami. He has also exhibited his work in museums in Spain, Puerto Rico, Russia and Argentina. Cambre has been awarded residencies at the Headlands Center for the Arts in Sausalito, CA, and at the National Studio Program in P.S. 1/MoMA, as well as artist grants from the New York Foundation for the Arts, the National Association of Latino Arts and Culture, the New Jersey Council on the Arts  and the Research Foundation of the City University of New York. His work is in the collections of the Whitney Museum and the Museo de Arte de Puerto Rico. Cambre's oeuvre has been discussed in publications such as the New York Times, Washington Post, New York Magazine, Tema Celeste, Sculpture Magazine, Arts Monthly, and Art Nexus
among others.

Publications
Black Box (2016; ) is Cambre's first published photo book.
Vacuus Bacchus (2016; ) is a series of color-tinted black & white photographs which explores the relation between Eros and Nothingness.
Soundtrack (2018; ) Cambre's Soundtrack interplays with the structural systems of communication (spatial, graphic, musical and linguistic) and the unfolding points where they deconstruct and open up to new visual and poetic possibilities.
Chamber Music (2020; ) is Cambre's fourth publication, taking to a new level the explorations of his previous book, Soundtrack. Chamber Music presents works raging from photography, painting and text to architectural drawings and indeterminate music notation.

References

External links
Official site

Spanish artists
American experimental filmmakers
Artists from San Juan, Puerto Rico
School of the Art Institute of Chicago alumni
University of Puerto Rico alumni
Living people
American video artists
Puerto Rican sculptors
Year of birth missing (living people)


B-cell CLL/lymphoma 9 protein is a protein that in humans is encoded by the BCL9 gene.

Function

BCL9, together with its paralogue gene BCL9L (BCL9 like or BCL9.2), have been extensively studied for their role as transcriptional beta-catenin cofactors, fundamental for the transcription of Wnt target genes.

Recent work, using the mouse (Mus musculus) and Zebrafish (Danio rerio) as model organisms, identified an ancient role of BCL9 and BCL9L as key factors required for cardiac development. This work emphasises the tissue-specific nature of the Wnt/β-catenin mechanism of action, and implicates alterations in BCL9 and BCL9L in human congenital heart defects.

BCL9 and BCL9L have been shown to take part in other tissue-specific molecular mechanisms, showing that their role in the Wnt signaling cascade is only one aspect of their mode of action.

The conserved homology domain HD1 of BCL9 (and BCL9L) has recently been shown to be interacting with TBX3 in the context of intestinal carcinogenesis; this interaction mediates some tissue-specific signalling functions of the protein.

Clinical significance

BCL9 is associated with B-cell acute lymphoblastic leukemia. It may be a target of translocation in B-cell malignancies with abnormalities of 1q21. The overexpression of BCL9 may be of pathogenic significance in B-cell malignancies.

BCL9 and BCL9L are potential clinical targets for human cancers; for instance, the gene expression changes that they promote is associated with a poor outcome in colorectal cancer.

Like BCL2, BCL3, BCL5, BCL6, BCL7A, and BCL10, it has clinical significance in lymphoma.

Common variations in the BCL9 gene, which is in the distal area, confer risk of schizophrenia and may also be associated with bipolar disorder and major depressive disorder.

BCL9, together with the paralogue protein BCL9l and PYGO2 also have cytoplasmic functions during tooth development and is particularly important for the formation of enamel. Mice lacking both Pygo1 and Pygo2 or both Bcl9 and Bcl9l develop teeth, a process that requires Wnt/β-catenin transcriptional regulation, but the enamel is structurally disorganized and contains less iron than teeth from control mice. Bcl9, Bcl9l, and Pygo2 are present in the cytoplasm of ameloblasts, the cells that secrete enamel proteins, and colocalize in these cells with amelogenin, the main component of enamel, encoded by the AMELX gene, which has been already implicated as a causative factor of Amelogenesis Imperfecta in humans. Bcl9 interacts with amelogenin and proteins involved in exocytosis and vesicular trafficking, suggesting that these proteins function in the trafficking or secretion of enamel proteins. Therefore, Bcl9, Bcl9l, and Pygo2 have cytoplasmic functions distinct from their roles as transcriptional cofactors downstream of Wnt signaling. This new discovery might improve our understanding for the treatment of human caries.

Related gene problems
1q21.1 deletion syndrome
1q21.1 duplication syndrome

References

Further reading

External links


60S ribosomal protein L26 is a protein that in humans is encoded by the RPL26 gene.

Function

Ribosomes, the organelles that catalyze protein synthesis, consist of a small 40S subunit and a large 60S subunit. Together these subunits are composed of 4 RNA species and approximately 80 structurally distinct proteins. This gene encodes a ribosomal protein that is a component of the 60S subunit. The protein belongs to the L24P family of ribosomal proteins. It is located in the cytoplasm. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome and the human paralog RPL26L1.

Interactions

RPL26 has been shown to interact with Mdm2.

See also
Eukaryotic translation
60S ribosomal subunit

References

Further reading

External links
 PDBe-KB provides an overview of all the structure information available in the PDB for Human 60S ribosomal protein L26

Ribosomal proteins


60S ribosomal protein L37 is a protein that in humans is encoded by the RPL37 gene.

Ribosomes, the organelles that catalyze protein synthesis, consist of a small 40S subunit and a large 60S subunit. Together these subunits are composed of 4 RNA species and approximately 80 structurally distinct proteins. This gene encodes a ribosomal protein that is a component of the 60S subunit. The protein belongs to the L37E family of ribosomal proteins. It is located in the cytoplasm. The protein contains a C2C2-type zinc finger-like motif. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome.

References

Further reading

External links

Ribosomal proteins


O Homem do Sputnik is a Brazilian comedy film from 1959 about a man (played by Oscarito) who tries to sell a UFO that lands on his house. Spies tail him, as they suspect it is a Russian Sputnik satellite. Norma Bengell also stars, performing a parody of Brigitte Bardot.

Plot
A couple of redneck egg traders, Anastácio and Cleci, are surprised by a bang in their chicken coop. Anastácio finds a metallic globe among his chickens. The next day, Cleci reads in the newspaper about the accident with the Russian satellite Sputnik and recognizes in the photograph an object similar to the one that fell in her backyard. Anastácio takes the globe to the pawnshop and shows it to the employee Dorinha. She calls the newspaper where her boyfriend Nelson works and tells him the fact.

Alberto, an unscrupulous journalist, overhears the conversation between the couple and tells the news to the head of the newspaper. Nelson goes to find Anastácio and asks him to hide the object. Anastácio places him inside the well. The news that Sputnik crashed in Brazil makes the front page of the newspapers. Anastácio and Clecy become celebrities. They stay at the Copacabana Palace, where they receive proposals from groups of Russians, Americans and French who try to seduce Anastácio, introducing him to the French singer Bebe.

The excessive interests of foreigners in the satellite drive the two crazy. Anastácio is kidnapped by the French and Nelson by the Americans. They run away and return to Anastácio's house. Russians, Americans and French follow them, fighting for the valuable trophy, which nobody knows where it is. Anastácio reveals the location where Sputnik is and everyone gets excited. They find nothing in the well. As he passed by, the sexton says he took the Sputnik and turned it into a lightning rod for the church. The foreign agents leave disappointed and Anastácio Cleci returns home, but they come across the real Sputnik that had just fallen into the chicken coop.

References

"O Homem do Sputnik", at Brazilian Cinemateca

1959 comedy films
Brazilian comedy films
1959 films


George John Rehring (June 10, 1890 – February 29, 1976) was an American prelate of the Roman Catholic Church. He served as bishop of the Diocese of Toledo in Ohio from 1950 to 1967.  He previously served as an auxiliary bishop of the Archdiocese of Cincinnati in Ohio from 1937 to 1950.

Biography

Early life and education
Rehring was born on June 10, 1890, in Cincinnati, Ohio, to Bernard L. and Mary A. (née Sander) Rehring. He attended St. Gregory's Preparatory Seminary and Mount St. Mary's Seminary, both in Cincinnati.

Priesthood
Rehring was ordained to the priesthood by Archbishop Henry Moeller for the Archdiocese of Cincinnati on March 28, 1914. He served as a curate at St. Mary's Parish in Hillsboro, Ohio, before being assigned to SS. Peter and Paul Parish in Reading, Ohio. In 1921, he received his first pastorate at Guardian Angels Parish in Cincinnati.

Rehring became professor of theology at Mount St. Mary's Seminary in 1923. From 1926 to 1928, he continued his studies at the Pontifical University of St. Thomas Aquinas, Angelicum in Rome, where he earned a Doctor of Sacred Theology degree. He served as rector of Mount St. Mary's Seminary from 1931 to 1940. He was named a domestic prelate in 1932.

Auxiliary Bishop of Cincinnati
On August 6, 1937, Rehring was appointed auxiliary bishop of the Archdiocese of Cincinnati and titular bishop of Lunda by Pope Pius XI. He received his episcopal consecration on October 7, 1937, from Archbishop John T. McNicholas, with Bishops Joseph H. Albers and Urban John Vehr serving as co-consecrators. As an auxiliary bishop, he served as pastor of St. Mary's Parish in the Hyde Park section of Cincinnati from 1940 to 1950.

Bishop of Toledo
Rehring was named the fourth bishop of the Diocese of Toledo by Pope Pius XII on July 16, 1950. Rehring attended all four sessions of the Second Vatican Council in Rome between 1962 and 1965. On February 25, 1967, Pope Paul VI accepted Rehring's resignation as bishop of Toledo and appointed him titular bishop of Tunnuna, a post he resigned on December 31, 1970.

George Rehring died on February 29, 1976, at age 85.

References

1890 births
1976 deaths
The Athenaeum of Ohio alumni
Roman Catholic Archdiocese of Cincinnati
Roman Catholic bishops of Toledo
20th-century Roman Catholic bishops in the United States
Participants in the Second Vatican Council
Religious leaders from Cincinnati
Roman Catholic Diocese of Toledo
Roman Catholic titular bishops of Tunnuna


60S ribosomal protein L37a is a protein that in humans is encoded by the RPL37A gene.

Ribosomes, the organelles that catalyze protein synthesis, consist of a small 40S subunit and a large 60S subunit. Together these subunits are composed of 4 RNA species and approximately 80 structurally distinct proteins. This gene encodes a ribosomal protein that is a component of the 60S subunit. The protein belongs to the L37AE family of ribosomal proteins. It is located in the cytoplasm. The protein contains a C4-type zinc finger-like domain. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome.

References

Further reading

External links

Ribosomal proteins


Dombås Station () is a railway station located at Dombås in Dovre, Norway. The station is located on the Dovre Line as well as serving as the terminal station for the Rauma Line. The station is served by express trains on the Dovre Line and regional trains on the Rauma Line. The station was built in 1913 when the Dovre Line was extended to Dombås.

The restaurant was taken over by Norsk Spisevognselskap on 15 November 1924. The building burned down on 23 April 1940 during the German occupation of Norway. A kiosk was immediately opened, and remained in use until the new station building and restaurant opened on 1 July 1941.

The first American killed in World War II, Captain Robert M. Losey, lost his life here on April 21, 1940, when a German aircraft bombed the station.

References

Railway stations in Oppland
Railway stations on the Dovre Line
Railway stations on the Rauma Line
Railway stations opened in 1913
1913 establishments in Norway
Dovre
Railway stations in Norway opened in the 1910s


Superabundance is the second full-length album by Young Knives, released in the United Kingdom on 10 March 2008. The album reached number twenty-eight in the UK Albums Chart.

The tracks "Terra Firma" and "Up All Night" were released as singles prior to the album launch. "Turn Tail" was the next single released on 19 May 2008.

The closing track "Current of the River" is a re-recorded version of the B-side to "She's Attracted To".

The cover of the album was made in London. 17-year-old Brant Dryver, a stunt rider from the Moto-Stunts International team, did the burn out stunt on the bike. The photographer wanted smoke and fire from the tyre so the bike's rear wheel needed to be placed on wood so it could burn.

Track listing
 "Fit 4 U" – 3:16
 "Terra Firma" – 2:48
 "Up All Night" – 2:58
 "Counters" – 4:11
 "Light Switch" – 3:47
 "Turn Tail" – 4:44
 "I Can Hardly See Them" – 3:07
 "Dyed in the Wool" – 3:10
 "Rue the Days" – 3:46
 "Flies" – 1:39
 "Mummy Light the Fire" – 4:04
 "Current of the River" – 5:24
 "Long Cool Drinks by the Pool" - 3:10 (following 2 minutes of silence after "Current of the River")
The US edition of the album also contains the b-sides of the "Terra Firma" and "Up All Night" singles.

Charts

Album

Singles

Special editions

Bonus DVD
A CD and DVD version is available featuring videos made by the band for each track of the album.

Special 7" single
A special acoustic version of "Turn Tail" was released on vinyl on 19 May 2008. The version was recorded directly onto vinyl in one take, at Westbourne Studios in London. This process is not believed to have been undertaken commercially since the 1970s by Warsaw Pakt.

References

2008 albums
Young Knives albums
Transgressive Records albums
Albums produced by Tony Doogan


Vacuolar protein sorting-associated protein 52 homolog is a protein that in humans is encoded by the VPS52 gene.

This gene encodes a protein that is similar to the yeast suppressor of actin mutations 2 gene. The yeast protein forms a subunit of the tetrameric Golgi-associated retrograde protein complex that is involved in vesicle trafficking from both early and late endosomes, back to the trans-Golgi network. This gene is located on chromosome 6 in a head-to-head orientation with the gene encoding ribosomal protein S18.

References

Further reading


SEC14-like protein 1 is a protein that in humans is encoded by the SEC14L1 gene.

The protein encoded by this gene belongs to the SEC14 cytosolic factor family. It has similarity to yeast SEC14 and to Japanese flying squid RALBP which suggests a possible role of the gene product in an intracellular transport system.

References

Further reading


Harald Deilmann (30 August 1920 – 1 January 2008) was a German architect.

Born in Gladbeck, Westphalia, Deilmann was best known for his work on public spaces, such as opera houses and museums, throughout Germany and worldwide. He was a member of the Akademie der Künste (Academy of the Arts) in Berlin, as well as the Deutsche Akademie für Städtebau und Landesplanung (German Academy for Urban and Regional Planning) in Hanover, Germany.

He was an associate of Heinrich Bartmann (1951–1953) and joined the Architektenteam Münster (Harald Deilmann, Max von Hausen, ,  in the competition for the theater Münster in 1953. He left the team before the opening of the theater Münster to start his own office in 1956. He took part in the development of his home town Münster in the time of the German Wirtschaftswunder 1950–1975. As a protagonist of postwar modernism he taught architecture at the Technical University Stuttgart and Dortmund.

Deilmann officially retired in 1985 but continued to do freelance work until his death in Münster.

Selected awards
1962 grand prize for North Westphalia architecture
1998 Cross of the White Rose, Helsinki, Finland.

Selected projects
 Theater:
 1952–1955: Stadttheater Münster
 1959–1988: Aalto Theatre, Essen (nach Alvar Aalto)
 Theater in Tokyo
 City Halls:
 1957: Rathaus Nordwalde
 1971–1974: Rathaus Rheda-Wiedenbrück
 Rathaus Gronau, North Rhine-Westphalia
 Schools and Universities
 Schülerinternat Münster
 Bielefeld University (competition)
 Martin-Luther-Schule Bielefeld
 Realschule Lemgo
 Metallberufsschule
 John F. Kennedy School, Berlin
 Museums
 Clemens-Sels-Museum Neuss
 Banks:
 WestLB Dortmund
 Town or urban planning:
 Stadtkern Werne
 Allwetterzoo Münster
 Office Buildings:
 Kreishaus Münster
 Verwaltung Nordwest Lotto Münster
 Hauptverwaltung LVA Rheinprovinz Düsseldorf
 Hauptverwaltung WestLB Münster, Düsseldorf und Dortmund
 Verwaltungsgebäude Wohnbauförderungsanstalt Düsseldorf
 Verwaltung Volkswohl-Bund in Dortmund
 Hospitals:
 Aggertalklinik Engelskirchen
 Städt. Krankenhaus Siegburg
 Fachklinikum Bad Salzuflen, Ahlbeck Reingau
 St.-Barbara-Krankenhaus Gladbeck
 Miscellaneous:
 1979–1981: Rheinturm Düsseldorf

External links

Architekt Deilmann obituary

1920 births
2008 deaths
People from Gladbeck
20th-century German architects
People from the Province of Westphalia
University of Stuttgart alumni
Academic staff of the University of Stuttgart
Academic staff of the Technical University of Dortmund
Academic staff of the University of Hanover
Commanders Crosses of the Order of Merit of the Federal Republic of Germany


John Cottam (born 5 June 1950, Warsop) was an English professional footballer who played as a defender. He played in The Football League for five clubs and later became a manager in non–league football.

Playing career
Cottam began his career with Nottingham Forest, whom he signed professional forms with in April 1968. He made his debut in the 1970–71 season when the club were in The First Division. Apart from loan spells with Mansfield Town and Lincoln City, Cottam remained at Forest until August 1976, making nearly 100 league appearances in the process.

Cottam then moved on to Chesterfield, where he played regularly for three years in Division Three. In July 1979 he moved to divisional rivals Chester for £12,500, making his debut in a Football League Cup tie against Walsall the following month. In his first season, he missed just one of Chester's 58 first-team games and helped the Blues reach the FA Cup fifth round. He remained a regular for the next two years with Trevor Storton his regular defensive partner.

Ahead of the 1982–83 season, Cottam moved to Alliance Premier League side Scarborough as player–manager, taking Chester players David Burns and Brynley Jones with him. His first season saw the club finish as runners–up in the Bob Lord Trophy, with the Seadogs going on to win the competition the following season. However, Cottam was sacked in November 1984, shortly after an FA Cup defeat to Tow Law Town.

After Playing career
After a spell playing for Burton Albion, Cottam joined the Metropolitan Police force in July 1985, becoming a police sergeant. He began playing for the Metropolitan Police in the Isthmian League. He played for three years and then became coach at the start of the 1992–93 season. Cottam became club manager in 1995 for two years.

John now works for Chelsea Football Club in Security as their Compliance Officer.

Honours

Scarborough

Bob Lord Trophy: Winners 1983–84; runners-up 1982–83.

External links
Nottingham Forest 'Where are they now' feature
Scarborough FC managers list

Bibliography

References

1950 births
Living people
English Football League players
National League (English football) players
Men's association football defenders
Nottingham Forest F.C. players
Mansfield Town F.C. players
Lincoln City F.C. players
Chesterfield F.C. players
Chester City F.C. players
Scarborough F.C. players
Burton Albion F.C. players
Metropolitan Police F.C. players
English football managers
Scarborough F.C. managers
Metropolitan Police F.C. managers
Metropolitan Police officers
People from Warsop
Footballers from Nottinghamshire
English men's footballers


Western Cove may refer to

Western Cove, Newfoundland and Labrador, a community in Canada
Western Cove, a body of water in Nepean Bay, South Australia


Ubiquitin-conjugating enzyme E2 O is a protein that in humans is encoded by the UBE2O gene.

UBE2O functions during terminal erythroid differentiation to eliminate generic cellular components in parallel with abundant synthesis of hemoglobin.

References

Further reading


The Sa Huynh Culture Museum () is located in Hội An, in the Quảng Nam Province of central Vietnam. It is a museum showcasing the pre-historic Sa Huỳnh culture, showcasing terracotta work that has been found in the area.

The museum was established in 1994, and displays a unique collection of artefacts from Sa Huynh culture, considered to be the first settlers of the port town, who cooperated and traded with countries in Southeast Asia, South India and China. This collection provides visitors with useful information about the ancient Sa Huynh culture's inhabitants and is mostly related to burial customs, conceptions of life and death, the developmental history of the region, and relationships with other cultures. Of particular significance is a collection from Bai Ong - a site on Cham Island - which traces Sa Huynh culture back by 3000 years. These collections are considered the largest and most unusual collection of Sa Huynh artefacts in Vietnam.

References

Literature

External links
 Frommer's | Sa Huynh Culture Museum
 Sa Huynh Museum (Vietnamese) - Centre for Cultural Heritage Management and Preservation

Museums in Hoi An


Spermatogenesis-defective protein 39 homolog is a protein that in humans is encoded by the VIPAS39 gene. This protein is involved in the sorting of lysosomal proteins. Mutations in this gene are associated with ARCS2 (arthrogryposis, renal dysfunction, and cholestasis-2). Alternative splicing results in multiple transcript variants.

References

External links

Further reading


Protein Muted homolog is a protein that in humans is encoded by the MUTED gene.

Function

This gene encodes a component of BLOC-1 (biogenesis of lysosome-related organelles complex 1). Components of this complex are involved in the biogenesis of organelles such as melanosomes and platelet-dense granules. A mouse model for Hermansky–Pudlak syndrome is mutated in the murine version of this gene. Some transcripts of the downstream gene TXNDC5 overlap this gene, but they do not contain an open reading frame for this gene.

Interactions

MUTED has been shown to interact with BLOC1S2, Dysbindin and PLDN.

References

Further reading


Polypeptide N-acetylgalactosaminyltransferase 11 is an enzyme that in humans is encoded by the GALNT11 gene.

The GALNT11 gene contains 10 exons. An important paralog of this gene is GALNTL5.

References

Further reading


Cytokine receptor-like factor 2 (also known as TSLP receptor, TSLP-R) is a protein that in humans is encoded by the CRLF2 gene. It forms a ternary signaling complex with TSLP and interleukin-7 receptor-α, capable of stimulating cell proliferation through activation of STAT3, STAT5 and JAK2 pathways and is implicated in the development of the hematopoietic system. Rearrangement of this gene with immunoglobulin heavy chain gene (IGH) (chromosome 14), or with P2Y purinoceptor 8 gene (P2RY8) (chromosome X or Y) is associated with B-progenitor- and Down syndrome- acute lymphoblastic leukemia (ALL).

Cytokine signals are mediated through specific receptor complexes, the components of which are mostly members of the type I cytokine receptor family. Type I cytokine receptors share conserved structural features in their extracellular domain. Receptor complexes are typically heterodimeric, consisting of alpha chains, which provide ligand specificity, and beta (or gamma) chains, which are required for the formation of high-affinity binding sites and signal transduction.[supplied by OMIM]

References

Further reading

External links


Transmembrane BAX inhibitor motif-containing protein 1 is a protein that in humans is encoded by the TMBIM1 gene.

References

Further reading


The 1936 football (soccer) season was the 35th season of competitive football in Brazil.

Campeonato Paulista

In 1936, there were two different editions of the Campeonato Paulista. One was organized by the Associação Paulista de Esportes Atléticos (APEA) while the other one was organized by the Liga Paulista de Foot-Ball (LPF).

APEA's Campeonato Paulista

Final Standings

Portuguesa declared as the APEA's Campeonato Paulista champions.

LPF's Campeonato Paulista

The LPF's Campeonato Paulista final was played between Palestra Itália-SP and Corinthians.

Palestra Itália-SP declared as the LPF's Campeonato Paulista champions by aggregate score of 3-1.

Campeonato Carioca

In 1936, there were two different editions of the Campeonato Carioca. One was organized by the Federação Metropolitana de Desportos (FMD) while the other one was organized by the Liga Carioca de Foot-Ball (LCF).

FMD's Campeonato Carioca

The FMD's Campeonato Carioca final was played between Vasco da Gama and Madureira.

Vasco da Gama declared as the FMD's Campeonato Carioca champions by the aggregate score of 4-3.

LCF's Campeonato Carioca

The LCF's Campeonato Carioca final was played between Fluminense and Flamengo.

Fluminense declared as the LCF's Campeonato Carioca champions by the aggregate score of 7-4.

State championship champions

Other competition champions

Brazil national team
The following table lists all the games played by the Brazil national football team in official competitions and friendly matches during 1936.

References

 Brazilian competitions at RSSSF
 1936 Brazil national team matches at RSSSF

Seasons in Brazilian football
Brazil


Minimal residual disease (MRD) is the name given to small numbers of leukaemic cells (cancer cells from the bone marrow) that remain in the person during treatment, or after treatment when the patient is in remission (no symptoms or signs of disease). It is the major cause of relapse in cancer and leukemia. Up until a decade ago, none of the tests used to assess or detect cancer were sensitive enough to detect MRD. Now, however, very sensitive molecular biology tests are available, based on DNA, RNA or proteins. These can measure minute levels of cancer cells in tissue samples, sometimes as low as one cancer cell in a million normal cells.

In cancer treatment, particularly leukaemia, MRD testing has several important roles: determining whether treatment has eradicated the cancer or whether traces remain, comparing the efficacy of different treatments, monitoring patient remission status as well as detecting recurrence of the leukaemia or cancer, and choosing the treatment that will best meet those needs.

The tests are not simple, are often part of research or trials, and some have been accepted for routine clinical use.

Background: the problem of minimal residual disease (MRD)

Most research on MRD has been done on leukaemia, particularly two types: adult chronic myeloid leukemia, and childhood acute lymphoblastic leukemia (the most common childhood cancer).

Leukemia is a cancer of cells in the blood, and primarily affects the bone marrow where they are made. For most human leukemias, the cause is not known. Risk factors can include chemicals and X-rays.

Leukemia involves a genetic abnormality that can begin in a single cell and then multiply rapidly, leading to a disruption in the proportion of cell types in the blood. When a bone marrow sample is drawn, leukemic cells can be viewed under a microscope.  Leukemic cells look like normal immature blood cells, and healthy marrow is often 1–2% immature (blasts) cells. However, in leukaemia, there are abnormally high numbers of immature cells, making up 40–90% of marrow. Additional examination of the bone marrow by tests including flow cytometry and FISH are necessary to diagnose the specific malignancy.

Symptoms do not occur until the disease is advanced, and there are 1 kg  or 1,000,000,000,000 leukemic cells in the body.

The initial five weeks of treatment kill most leukaemic cells, and the marrow begins to recover. Immature white blood cells may be present in the patient, although they are not necessarily malignant cells. In most cases, a few leukemic cells (approximately 0.001%) survive this treatment, and persist in the marrow for months or years. Cancerous cells can be identified by DNA-based or immunological tests, but they can not be identified as cancerous when viewed under a microscope.

About 30 years ago, leukemia was universally fatal. Patients were treated for a few weeks (rather than months or years as at present), producing remission, but nearly all patients relapsed after a few weeks or months. It is now known that minimal residual disease can regrow once treatment was stopped.  Genetic  tests can confirm the leukemic cells at relapse are descendants of those present when the disease first appeared.

Doctors aim to prevent relapse from occurring. Currently, most children do not relapse – the disease is "cured" at first attempt. If the disease relapses, it is usually more resistant to treatment than when first diagnosed. Patients who have relapsed once are at high risk of relapse in the future, and they may not respond as well to drugs they received in the past.

Tests which uncover minimal residual disease (one cancerous cell in a population of one million normal cells) are helpful for directing treatment and preventing relapse. A single remaining leukemic cell can be fatal, as malignant cells divide without control.  Conditioning regimens can continue as long as the patient is healthy enough to sustain damage by cytotoxic treatments.

Most research on MRD was done on leukemia and lymphomas. Researchers hope that the discoveries made can be applied to understand and treat other cancers.

Techniques for measuring minimal residual disease in leukaemia

DNA-based tests

These are based on detecting a leukaemic specific DNA sequence.  Generally this is achieved through the use of the polymerase chain reaction, a highly sensitive technique that underpins much of molecular biology. The DNA sequence chosen may contribute to the genesis of the leukaemia, or may simply be linked to it.

The markers used for DNA-based testing are often chromosomal translocations such as t(14;18) involving BCL2 and t(11;14) involving BCL1 (CCND1).  Other genes utilized for MRD detection include microsatellites, immunoglobulin and T cell receptor.

Some new techniques use Next-Generation Sequencing to detect MRD.

RNA-based tests

These are based on detecting a leukemic specific RNA sequence.  Generally this is achieved through the use of reverse transcription of the RNA followed by polymerase chain reaction.  RNA-based tests are normally utilized when a DNA test is impractical.  For example, the t(9;22) BCR-ABL translocation may occur over a large length of the chromosome which makes DNA-based testing difficult and inefficient.  However, RNA is a much less stable target for diagnostics than DNA and requires careful handling and processing.

The markers used for RNA-based testing are almost exclusively chromosomal translocations such as t(9;22) BCR-ABL, t(15;17) PML-RARA and t(12;21) ETV6-RUNX1 (TEL-AML1).

Patient-specific testing

Patient-specific MRD detection using immunoglobulin (IG) or T-cell receptors (TCR) is gaining popularity as a way of measuring MRD in leukemias that do not contain a chromosomal translocation or other leukemic specific marker.  In this case, the leukemic specific IG or TCR clone is amplified using PCR and the variable region of the IG or TCR is sequenced.  From this sequence, PCR primers are designed that will only amplify the specific leukemic clone from the patient.

Both the DNA and RNA based tests require that a pathologist examine the bone marrow to determine which leukaemic specific sequence to target.  Once the target is determined, a sample of blood or bone marrow is obtained, nucleic acid is extracted, and the sample analyzed for the leukaemic sequence. These tests are very specific, and detect leukaemic cells at levels down to one cell in a million, though the limit typically achieved is 1 in 10,000 to 1 in 100,000 cells. For comparison, the limit of what one can detect using traditional morphologic examinations using a microscope is about 1 cell in 100.

Immunological tests

Immunological-based testing of leukaemias utilizes proteins on the surface of the cells. White blood cells (WBC) can show a variety of proteins on the surface depending upon the type of WBC.  Leukaemic cells often show quite unusual and unique combinations (leukemic phenotype) of these cell surface proteins. These proteins can be stained with fluorescent dye labeled antibodies and detected using flow cytometry.  The limit of detection of immunological tests is generally about 1 in 10,000 cells and cannot be used on leukaemias that don't have an identifiable and stable leukaemic phenotype.

Use of and common targets in detection in different leukaemias, lymphomas and solid tumors

Acute lymphoblastic leukaemia (ALL)

Targets:
t(9;22) BCR-ABL, t(12;21) ETV6-RUNX1 (TEL-AML1), Patient specific assays for immunoglobulin and T cell receptor genes

Uses: Chromosomal translocation MRD detection is widely used as a standard clinical practice.  Patient specific assays are gaining acceptance but are still generally only used in research protocols.

Acute myeloid leukaemia (AML)

Targets:
t(15;17) PML-RARA, t(8;21) AML1-RUNX1T1 (AML-ETO), inv(16)

Uses: Chromosomal translocation MRD detection widely used as a standard clinical practice.

Chronic lymphocytic leukaemia

Targets:
Cell surface proteins, patient-specific assays for immunoglobulin and T cell receptor genes

Uses: Immunological methods are gaining wider use as more advanced flow cytometers are utilized for clinical testing.  Patient specific assays are still generally only used in research protocols.

Chronic myelogenous leukemia

Target:
t(9;22) BCR-ABL

Uses: MRD detection of the t(9;22) is considered standard of care for all patients with CML and is extremely valuable for patients being treated with imatinib mesylate (Gleevec/Glivec).

Follicular lymphoma

Targets:
t(14;18) IgH/BCL2, Patient specific assays for immunoglobulin and T cell receptor genes.

Uses: The t(14;18) is regularly used for MRD detection.  Patient specific assays are still generally only used in research protocols.

Mantle cell lymphoma

Targets:
t(11;14) IgH/CCND1 (IgH/BCL1), patient-specific assays for immunoglobulin and T cell receptor genes

Uses: The t(11;14) is regularly used for MRD detection, but the assay can only reliably detect 40–60%  of the t(11;14) translocations.  Patient-specific assays are still generally only used in research protocols.

Multiple myeloma

Targets:
M-protein levels in blood, patient-specific assays for immunoglobulin and T cell receptor genes (high levels of somatic hypermutation often prevent this assay from reliably working).

Uses: M-protein level in the blood is standard of care and is used for almost all patients with multiple myeloma.
Patient-specific assays are still generally only used in research protocols.

Solid tumors

Research into MRD detection of several solid tumors such as breast cancer and neuroblastoma has been performed.  These assays have been used to sample lymph nodes and blood for residual or metastatic tumor cells.  Applicable targets for MRD detection have been more difficult to determine in solid tumors and the use of MRD in solid tumors is much less advanced than the use in leukemia and lymphoma.

New research uses Whole genome sequencing and Artificial Intelligence to find MRD across multiple solid tumors.

Animal species other than humans

Leukaemias and lymphomas could potentially be monitored similarly in non-human animals, however, no known evidence of such veterinary applications exists to date.

Significance

Level of MRD is a guide to prognosis or relapse risk

In some cases, the level of MRD at a certain time in treatment is a useful guide to the patient's prognosis. For instance, in childhood leukaemia, doctors traditionally take a bone marrow sample after five weeks, and assess the level of leukaemia in that. Even with a microscope, they were able to identify a few patients whose disease had not cleared, and those patients received different treatment. MRD tests also make use of this time, but the tests are much more sensitive.

When past patients were studied, patients with high levels at this stage - here "high" means often leukaemia more than 1 cell in 1000 – were at risk of relapse. Patients with levels below 1 in 100,000 were very unlikely to relapse. For those in between, some relapsed. This led to the idea that MRD testing could predict outcome, and this has now been shown. The next step is whether, having identified a patient whom standard treatment leaves at high risk, there are different treatments they could be offered, to lower that risk. Several clinical trials are investigating this.

Other research groups have looked at other times in treatment - e.g. 3 months, 6 months, one year, or end of current treatment (two years) and these can predict outcome also.

There are also a few scientific studies, showing that level of MRD after bone marrow transplant, shows the risk of relapsing.

Monitoring people for early signs of recurring leukaemia

Another possible use is to identify if or when someone starts to relapse, early, before symptoms come back. This would mean regular blood or marrow samples. This is being explored mainly in chronic myeloid leukaemia (CML), where one can study the leukaemia in blood, which is easier to sample regularly than bone marrow. The molecular tests can show tumour levels starting to rise, very early, possibly months before symptoms recur.  Starting treatment early might be useful: the patient will be healthier; fewer leukaemic cells to deal with; the cells may be  amenable to treatment, since at clinical relapse they have often become more resistant to drugs used.

Individualization of treatment

This whole area comes under individualization of treatment, or if one prefers, identification of risk factors. Currently, most patient receive the same treatment, but leukaemia is a very variable disease, and  different patients probably have widely different treatment needs, to eradicate the disease.

For instance, the initial five-week induction treatment might rapidly clear disease for some patients. For others, the same treatment might leave significant amounts of disease. Measuring MRD level helps doctors decide which patients need what. In other words, it identifies patients' individual risks of relapse, and can theoretically allow them to receive just enough treatment to prevent it.

Without MRD information, doctors can do nothing but give the same treatment to all patients. They know that this will be inadequate for some and excessive for others, but there is little else they can do, as it is not possible to tell who needs what.  Identification of risk factors, to help individualise treatment, is a big field in medicine.

Treatment
Generally the approach is to bring a cancer into remission first (absence of symptoms) and then try to eradicate the remaining cells (MRD). Often the treatments needed to eradicate MRD differ from those used initially. This is an area of much research.

It seems a sensible idea to aim to reduce or eradicate MRD. What is needed is evidence on which is the best method, and how well it works. This is emerging. Treatments which specifically target MRD can include:

 intensive conventional treatment with more drugs, or a different combination of drugs
 stem cell transplant, e.g.  marrow transplant. This allows more intensive chemotherapy to be given, and in addition the transplanted bone marrow may help eradicate the minimal residual disease
 immunotherapy
 monitoring the patient carefully for early signs of relapse. This is an area of active research in several countries.
 treatment with monoclonal antibodies which target cancer cells
 cancer vaccines

Areas of current research and controversies

Clinical usefulness of MRD tests

It is important that doctors interpreting tests, base what they say on scientific evidence.  If one visits hospital and gets tested for something - e.g. a blood count - most of the tests are used often, and have been done thousands or millions of times before, on many different people. The doctors reading the test results have a large body of evidence to interpret what the results mean. By contrast, MRD tests are new, and the diseases are uncommon. The tests have been done on relatively few people. Consequently, there is less evidence available to guide doctors in interpreting the tests, or basing treatment decisions on them. In plain English, this means the doctors are likely to be very cautious, and rely more on other tests which they know and trust, than these, at least at present, while evidence is accumulating.

Method for testing, and when to test

There are controversies about the best times to test, and the best test method to use. There are national and international approaches to standardize these. In childhood leukaemia and chronic myeloid leukaemia, there appears to be consensus emerging.

Is there such a thing as a safe level of MRD

There is also controversy about whether MRD is always bad, inevitably causing relapse, or whether sometimes low levels are 'safe' and do not regrow. It is usually assumed that cancer cells inevitably  grow and that if they are present disease usually develops. But there is some evidence from animal studies, that leukaemic cells can lie dormant for years in the body and do not regrow. For this reason, it may be that the goal of treating MRD may be to reduce it to a "safe" level - not to eradicate it completely.

Is MRD testing useful for all patients?

Some types of leukaemia are difficult to treat. In these, it is not clear how MRD testing would help. The patients may not do well on current treatment, but sometimes it is not clear what other treatment, if anything, might be better. There is thus an argument that as the test is not necessary: it might involve an additional procedure for the patient; it will contribute no useful information on treatment, it is not necessary.

Testing by hospitals and other labs

Where done

MRD testing is not yet a routine test, nor is it carried out in all places.

Currently most MRD testing - in Leukemia Research - is done during clinical trials, and would be funded as part of that trial, for patients enrolled on the trial.  The tests are specialised, so samples are usually sent to a central reference laboratory in each region or country. The tests are not done in most routine diagnostic labs, as they tend to be complex, and also would be used relatively infrequently.

Cost

MRD testing is technically demanding and time-consuming; the tests are expensive, so are usually available only through specialist centres, as part of clinical trials.

Availability of testing

At the time of writing (Jan 2017), MRD testing is available in some clinical trials in the UK, Europe, Australia, China and the US.

Interpretation of test results

Most clinical tests used to guide treatment - e.g. even a simple blood count - have been done millions of times, and doctors can interpret the results confidently, based on this extensive previous knowledge.  By contrast, MRD tests are new and have been carried out on relatively few people (a few thousand at most). Researchers and doctors are still building the extensive database of knowledge needed to show what MRD tests mean.

The consequence: unless a patient is enrolled on a trial which requires the test, clinicians tend to be somewhat cautious about requesting it, and cautious about interpreting the results. This is likely to change in future, as tests become more routine.

Resources

General
Minimal Residual Disease. Website. Modern MRD Detection Technologies. July 2013.
 Leukaemia Research Fund (United Kingdom)
Children with Leukaemia (United Kingdom)

Textbooks

Research papers

References

Leukemia


"In the Blood" is a song by American alternative rock group Better Than Ezra. It was released in June 1995 as the second single from the band's major-label debut album Deluxe. The song peaked at number four on the Billboard Modern Rock Tracks chart and number six on the Mainstream Rock Tracks chart. The song was not eligible to chart on the Hot 100 because no commercial single was made available for purchase. However, the song received enough radio airplay to peak at number 48 on the Hot 100 Airplay chart.

Music video
The music video for the song was directed by Frank W. Ockenfels III. As with "Good", the band's previous single, "In the Blood" saw radio success before the video aired on MTV.

Track listing
 "In the Blood" (Edit Remix)
 "In the Blood" (LP Version Remix)

Note: Promotional CD.

Chart performance

References

Better Than Ezra songs
1995 singles
Black-and-white music videos
Songs written by Kevin Griffin
1993 songs


Werner Kurt Rey (born October 6, 1943) is a UK-based Swiss businessman, financier and convicted fraudster. In 1976, Rey acquired the fashion house Bally, and subsequently sold it to the Oerlikon Bührle concern, which laid the foundation of his Omni Holding AG, which would at its peak have assets under management exceeding $4 billion.

Subsequently, his investor and venture capitalist career took off from that of an initiator of hostile take-overs to that of a USD billionaire white knight in various international M&A deals ranging from real estate to engineering works, electronics, media and financial services, in which he himself served occasionally as guarantor to institutional lenders.

Early life and education
Rey was born October 6, 1943, in Zurich, Switzerland. He was the son of a physician (MD) and initially wanted to enter medical studies at the University of Zurich, but failed the admissions exam. Instead he completed a commercial apprenticeship at the private bank Rüd, Blass & Cie. AG in Zurich, which was later merged with the wealth management of Deutsche Bank. Rey graduated best of his class.

Career
Rey launched his career while working for a London-based company from 1961 to 1963, which was followed by several non-executive and executive positions in Geneva, namely at the controversial investment firm Investors Overseas Service (IOS) founded by American financier Bernard Cornfeld in 1955, where he became deputy director. In 1969, he began to work as an independent consultant and corporate advisor, until 1975.  He also held a management role at an international bank.

In 1976, Rey, acquired share majority of the fashion house Bally and subsequently sold it to Oerlikon-Bührle, an industrial concern, with a profit of $60 million (which would be equivalent to $312 million in 2023). This laid the foundation for his Omni Holding AG which would soon turn into an industrial conglomerate with several thousand employees. Rey held controlling interest in Metallwerke Selve AG (Selve Metal Works) in Thun, media and publishing giant Jean Frey AG in Zurich, temporary employment agency Adia Interim (today a part of Adecco), commodity inspection comapany Inspectorate International as well as 30% of controlling interest in Sulzer.

Until 1990, Rey was a well respected Swiss financier, and had about $4 billion in assets under management.

Case against Werner K. Rey
During the recession of 1990/91 Omni Holding AG began having substantial financial issues. In 1991, the company became insolvent, and had to file bankruptcy. After Swiss authorities filed a case against Werner K. Rey on several allegations of fraud, falsification of documents, and fraudulent bankruptcy, he fled to The Bahamas, where he was arrested in 1996. This was among the most spectacular white collar crimes of Switzerland and one of the largest corporate bankruptcies similar to Swissair. He was subsequently extradited to Switzerland to face criminal justice.

In 1998, he was put on trial for an attempt to defraud the Cantonal Bank of Bern when Inspectorate went public and for fraudulent bankruptcy because he had reduced his private assets at the expense of the creditors - whether for appearances or with good intentions could not be clarified. Accordingly, the sentence of four years in prison was well below the ten years demanded by the prosecutor. Further proceedings for commercial fraud, forgery of documents and fraudulent bankruptcy expired in 2007. The pending proceedings were therefore dismissed. Rey kept the judiciary in suspense for years and owes the Canton of Bern around CHF 4.3 million in court costs alone.

Post-imprisonment release
Rey was released from prison on June 14, 2000.

Since his fraud trial and prison sentence, he has apparently returned to London (where his wife is from) and is again active in the field of participations and finance.

Private
Rey is married and resides in London.

References

Living people
1943 births


ATP-binding cassette sub-family G member 4 is a protein that in humans is encoded by the ABCG4 gene.

The protein encoded by this gene is included in the ATP-binding cassette transporter (ABC protein) superfamily. ABC proteins transport various molecules across extra- and intra-cellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). This protein is a member of the White subfamily and is expressed predominantly in liver tissue. The function has not yet been determined but may involve cholesterol transport. Alternate splice variants have been described but their full length sequences have not been determined.

ABCG4 has demonstrated, in vitro, to participate in the efflux of desmosterol and amyloid-β peptide (Aβ).  It is highly expressed in the brain, but its localization and function at the blood-brain barrier (BBB) level remain unknown.

See also
 ATP-binding cassette transporter

References

Further reading

External links

Solute carrier family