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Progesterone is an endogenous steroid and progestogen sex hormone involved in the menstrual cycle and embryogenesis of humans and other species. It belongs to a group of steroid hormones called the progestogens, is the major progestogen in the body. Progesterone has a variety of important functions in the body, it is a crucial metabolic intermediate in the production of other endogenous steroids, including the sex hormones and the corticosteroids, plays an important role in brain function as a neurosteroid. In addition to its role as a natural hormone, progesterone is used as a medication, for instance in menopausal hormone therapy, it was first prescribed in 1934. Progesterone is the most important progestogen in the body; as a potent agonist of the nuclear progesterone receptor the resulting effects on ribosomal transcription plays a major role in regulation of female reproduction. In addition, progesterone is an agonist of the more discovered membrane progesterone receptors, of which the expression has regulation effects in reproduction function and cancer although additional research is required to further define the roles.

It functions as a ligand of the PGRMC1 which impacts tumor progression, metabolic regulation, viability control of nerve cells. Moreover, progesterone is known to be an antagonist of the sigma σ1 receptor, a negative allosteric modulator of nicotinic acetylcholine receptors, a potent antagonist of the mineralocorticoid receptor. Progesterone prevents MR activation by binding to this receptor with an affinity exceeding those of aldosterone and glucocorticoids such as cortisol and corticosterone, produces antimineralocorticoid effects, such as natriuresis, at physiological concentrations. In addition, progesterone binds to and behaves as a partial agonist of the glucocorticoid receptor, albeit with low potency. Progesterone, through its neurosteroid active metabolites such as 5α-dihydroprogesterone and allopregnanolone, acts indirectly as a positive allosteric modulator of the GABAA receptor. Progesterone and some of its metabolites, such as 5β-dihydroprogesterone, are agonists of the pregnane X receptor, albeit weakly so.

In accordance, progesterone induces several hepatic cytochrome P450 enzymes, such as CYP3A4 during pregnancy when concentrations are much higher than usual. Perimenopausal women have been found to have greater CYP3A4 activity relative to men and postmenopausal women, it has been inferred that this may be due to the higher progesterone levels present in perimenopausal women. Progesterone modulates the activity of CatSper voltage-gated Ca2+ channels. Since eggs release progesterone, sperm may use progesterone as a homing signal to swim toward eggs; as a result, it has been suggested that substances that block the progesterone binding site on CatSper channels could be used in male contraception. Progesterone has a number of physiological effects. Estrogens through estrogen receptors induce or upregulate the expression of the PR. One example of this is in breast tissue, where estrogens allow progesterone to mediate lobuloalveolar development. Elevated levels of progesterone potently reduce the sodium-retaining activity of aldosterone, resulting in natriuresis and a reduction in extracellular fluid volume.

Progesterone withdrawal, on the other hand, is associated with a temporary increase in sodium retention due to the compensatory increase in aldosterone production, which combats the blockade of the mineralocorticoid receptor by the elevated level of progesterone. Progesterone has key effects via non-genomic signalling on human sperm as they migrate through the female tract before fertilization occurs, though the receptor as yet remain unidentified. Detailed characterisation of the events occurring in sperm in response to progesterone has elucidated certain events including intracellular calcium transients and maintained changes, slow calcium oscillations, now thought to regulate motility, it is produced by the ovaries. Progesterone has been shown to demonstrate effects on octopus spermatozoa. Progesterone is sometimes called the "hormone of pregnancy", it has many roles relating to the development of the fetus: Progesterone converts the endometrium to its secretory stage to prepare the uterus for implantation.

At the same time progesterone affects the vaginal epithelium and cervical mucus, making it thick and impenetrable to sperm. Progesterone is anti-mitogenic in endometrial epithelial cells, as such, mitigates the tropic effects of estrogen. If pregnancy does not occur, progesterone levels will decrease, leading, in the human, to menstruation. Normal menstrual bleeding is progesterone-withdrawal bleeding. If ovulation does not occur and the corpus luteum does not develop, levels of progesterone may be low, leading to anovulatory dysfunctional uterine bleeding. During implantation and gestation, progesterone appears to decrease the maternal immune response to allow for the acceptance of the pregnancy. Progesterone decreases contractility of the uterine smooth muscle; this effect contributes to prevention of preterm labor. A drop in progesterone levels is one step that facilitates the onset of labor. In addition progesterone inhibits lactation during pregnancy; the fall in progesterone levels following delivery is one of the triggers for milk production.


1958 BOAC Bristol Britannia crash

G-AOVD was a Bristol Britannia 312 operated by BOAC which crashed near Christchurch, Dorset in the south of England on Christmas Eve 1958, killing two of the five crew and all seven passengers. On 24 December 1958 much of the south of England was covered in thick fog making travel by any means hazardous. Many aircraft had to be diverted as visibility was below the minimum permissible distance at most of the airports on the south coast. To a pilot, less than aware of the conditions on the ground and the altitude at which they were flying, this fog would have an appearance similar to normal cloud cover. For the pilots of G-AOVD this may have added to the illusion that they were at a much higher altitude and that they were reading the instruments correctly; the aircraft departed from London Heathrow Airport at 10:10 am on a test flight to renew its certificate of airworthiness with 12 persons aboard including five crew. After completing the test, at 11:55 am, the crew requested clearance to descend from 12,000 feet to 3,000 feet for approach to Hurn Airport as an alternate destination due to poor weather at Heathrow.

3 minutes at 11:58 am, Hurn Airport lost contact with the aircraft as it struck the ground, crossing a road into a ploughed field, bringing down telephone lines and trees and alerting residents in the nearby villages. Upon realising they had lost contact with the aircraft, the controller at Hurn contacted the emergency services giving the last known position before contact was lost; the residents of Winkton and people living near Bransgore contacted emergency services saying they believed that they had heard the sound of a low flying aircraft and the sound of a crash. Around midday, the members of the volunteer fire service in Burley and Christchurch were alerted by an air raid siren calling them to the station to respond to the report of the crash; the initial report from Hurn Airport stated that they were unaware of the type of aircraft involved or how many passengers were being carried, that they believed the aircraft was to the north of the airport when it crashed. However, on receiving updated information on the reports from Winkton and Sopley the fire crews decided to start the search for the aircraft in that area.

The fire service searching in Winkton discovered the location of the wreckage after travelling a short distance along the Burley Road and finding telephone poles and cables, broken and dragged into a field off the road. A foot search was mounted and the crew spotted some broken trees along with aircraft debris and a fire; the crew chief sent a message to fire control to confirm the location of the crash and set up a rendezvous at a local public house to give emergency services a positive location. Another appliance, sent to Sopley to search there could not be contacted as it was not fitted with a radio. Another hindrance to the emergency effort was the lack of a four-wheel drive appliance which meant that the firemen had to attempt to drive an eight-ton vehicle over a ploughed field, which delayed the rescue. While this was going on, the crew chief and some of the crew from the first appliance on the scene continued to search on foot and found the remains of the cockpit with the injured co-pilot trapped inside.

They began to cut him free and as further emergency services arrived on the scene, a coordinated search and rescue effort was mounted over the site, fanning out and finding a further two survivors. The fire station was able to confirm what aircraft had been involved and the number of people on board at the time. Having received this information the emergency services were able to account for all the people involved and to continue putting out the fires; the crash was attributed to a failure on the part of the captain and first officer to establish the altitude of the aircraft before and during the descent. The Britannia aircraft was fitted with a three-handed altimeter which required a higher degree of concentration to read than was desirable; the crew misread the instrument believing that they were at 11,500 feet when they began descending, when in fact they were at only 1,500 feet. As a result, they flew the aircraft into the ground, obscured by fog at the time; the type of flight in which the aircraft was engaged was thought to be a contributing factor.

It was concluded that this crash was a controlled flight into terrain and that there were no defects with the aircraft or its systems which contributed to the crash. For this the failure to read the instruments rests with the captain; this was not the first crash involving a crew misreading this type of altimeter in this long distance, high altitude aircraft. As a direct result of this and other similar incidents, altimeters would now be required to display a cross-hatch or chequered flag when indicating an altitude below 1500 feet. Furthermore, all fire appliances in Christchurch would now be fitted with radios for improved communication, when four-wheel drive appliances became available, Christchurch was one of the first rural stations to be allocated one; as a result of the accident the Ministry of Transport issued a directive to replace all three-pointer altimeters in British registered aircraft which operated at over 20,000 feet before September 1959. This followed an investigation of the problems of interpretation of the display.

An interim flight safety warning was issued pending altimeter replacement which described the risk of misreading these altimeters as "most when the routine monitoring of the instrument panel has been interrupted. If this happened during cli

Max Colpet

Max Colpet was an American writer and lyricist of Russian-German descent. He was born to a Russian Jewish family in Königsberg in East Prussia. Due to the political situation at the time, he was stateless. In 1914 at the start of the war his family fled to the West. In 1928, with Erik Ode, he founded the cabaret Anti in Berlin. In the 1930s he fled again, his parents died during World War II in concentration camps. On 14 August 1953 he became an American citizen, but in 1958 he moved to Munich where he lived for the rest of his life. Among other writings, he wrote for the Münchner Lach- und Schießgesellschaft, a cabaret theatre founded by Sammy Drechsel and Dieter Hildebrandt, he had a lifelong friendship with Billy Wilder for. In Los Angeles, Colpet lived in the guest house behind Wilder's Beverly Hills house, 704 North Beverly Drive, until Wilder sold the house to Dr. Harry Lehrer and fashion designer Anne T. Hill in 1957 and moved to Century City. "Allein in einer großen Stadt" "Bitte geh nicht fort" – "Ne me quitte pas", "Der Boss ist nicht hier" "Hoppla, jetzt komm ich" "Kleine treue Nachtigall" – "Message to Martha/Michael" "Sag mir, wo die Blumen sind" – "Where Have All the Flowers Gone" "Der ewige Soldat" – Donovan: "Universal Soldier".

Joe Cassidy (footballer, born 1872)

Joseph Cassidy was a Scottish footballer who played as a forward. Born in Dalziel, Cassidy started his career with Motherwell Athletic before joining Blythe in 1890. In 1893, he was transferred to Newton Heath, where he played in the last four league games of the season, as well as a test match against Small Heath, in which he scored to keep Newton Heath in the First Division. After two months with the Heathens, he moved to Celtic. In 1895, he returned to Newton Heath. In seven seasons back with the club, Cassidy scored 99 goals, he went on to play for Manchester Middlesbrough. At the latter club, he would be captain for their first game at Ayresome Park scoring the first competitive goal at the new ground, he moved to Workington in 1906. GeneralDykes, Garth; the United Alphabet: A Complete Who's Who of Manchester United F. C. Leicester: ACL & Polar Publishing. ISBN 0-9514862-6-8. Specific

Hridayeshwar Singh Bhati

Hridayeshwar Singh Bhati is an Indian student who invented a six-player variant of chess at the age of 9 with assistance from his father. He earned a patent for his invention in 2012, making him the youngest patent-holder in India at that time. For his invention Bhati received the CavinKare Ability Special Recognition Award and the Sri Balaji Society's Child Innovator Award, he has since designed and received patents for twelve- and sixty-player versions of his game, with his boards capable of 100 distinct variations altogether. Besides circular chess, Bhati has developed a ramp system enabling easy access to vehicles for the disabled. In 2014 he was presented a Dr. Batra's Positive Health Award by Mahendra Singh Dhoni. Bhati uses a wheelchair, he credits his passion for invention to his admiration of British physicist Stephen Hawking: "I want to be like Hawking who became a famous scientist despite suffering from motor neuron disease." Bhati's version of multiplayer chess is played on a circular board with 228 white cells.

The 12 red spaces are not used. Up to six players in teams of two or three can play. Bhati's design employs all their moves. Individual armies are distinguished by colour; each player starts types of pieces as in standard chess. Non-pawn pieces start in their normal positions on the back ranks, with queens always placed to the left of kings. Pawns are placed on the rank in front of the pieces as in standard chess. Red spaces can not be passed through when moving or capturing; the multicoloured central area can be passed through but not occupied. It is considered a single "null" space, so a cell bordering it is considered adjacent to the cell on the direct opposite side of the null area; the king and pawn have their standard chess moves, unaffected when crossing the central null space, where a cell directly across is considered adjacent. A pawn promotes as normal. A rook moves horizontally along concentric rings of cells, vertically along files, including crossing the central null space and continuing along the same file in a straight line.

When moving horizontally, a rook cannot end its move on the same cell it started from. The queen vertically the same as a rook; when a queen or bishop moves diagonally and crosses the central null space to the opposite side, it must continue from a cell of the same colour it started from: it is moved one cell clockwise or anticlockwise after passing the null space, consistent with whether it began its diagonal movement in a clockwise or anticlockwise direction. When a player is checkmated or resigns, all their remaining pieces are removed from play. In games where teams compete, the last team standing is the winner. Circular chess

Endo contractualization

Endo refers to a short-term employment practice in the Philippines. It is a form of contractualization which involves companies giving workers temporary employment that last them less than six months and terminating their employment just short of being regularized in order to skirt on the fees which come with regularization; some examples of such benefits contractual workers don't get as compared to regularized workers are the benefits of having an employer and employee SSS, the Pag-ibig housing fund contribution, unpaid leaves, the 13th Month Pay, among others. Since the initial drafts of the Philippine Labor Code up until today, there has been no drastic action on contractualization; this topic on Endo has been the subject of many debates ranging through various presidencies each promising to end this exploitative labor practice with each presidents contribution being a minute change to the Philippine Labor Code. Stances on this issue are divided, there are some who point out how the practice is exploitative and illegal, others who say it's Contractualization is essential to economic growth, while there are others talking about how it affects the workers who are subject to it.

Despite its history having made the practice legal revisions to Philippine Labor Laws have deemed the practice illegal. However, despite the controversy it is still employed by major companies in the Philippines to cheapen labor fees; the word Endo is derived from an abridged version of the phrase "end of contract". Endo is sometimes referred to "5-5-5", referring to the number of months until a non-regular employee's termination or end of contract. Under the Labor Code of the Philippines, employers may employ people under a probationary status of not exceeding six months. Under this system, the worker's employment contract ends before the six month by their employer. After the six-month period, employees become regular workers, entitled to several health and insurance benefits prescribed by law. Contractualization is one of the most controversial labor practices in the Philippines. Since its adoption in 1974, the Labor Code has been amended and attached with several implementing texts; as of June 2016, there are an estimated 356,000 probationary workers in the Philippines.

A regular employee is defined by the 1974 Labor Code as one, “engaged to perform activities which are necessary or desirable in the usual business or trade of the employer,”There are two types of regular employees as per the Labor Code of the Philippines: those who are engaged to perform activities which are necessary or desirable in the usual business or trade of the employer. A regular employee is entitled to the following benefits: Social Security System Private companies are required to register all regular employees in the system; the SSS provides health insurances. Philippine Health Insurance Corporation Both private and public sector workers ought to be contributors to this service; the corporation sets aside contributions for medical insurance. Home Development Mutual Fund This agency allows provides housing loans with low interest, payable up to 30 years. Private and public firms are mandated to contribute to the fund on behalf of all its regular employees. 13th month pay, service leaves and maternity benefits, etc. union dues The above-mentioned pecuniary benefits are deducted by the employer from the gross monthly salary of the employee.

In addition to regular employment, probationary employment is possible through the Code. Under Article 2B1, probationary employment shall not exceed six months “unless it is covered by an apprenticeship agreement stipulating a longer period.” This would mean that any employee working over the stated or agreed period shall be considered as a regular employee. However, both regular and non-regular employees still enjoy security of tenure, pertaining to the Constitutional guaranty found in Sec. 3, Art. XIII of the 1987 Constitution that no employee, whether regular or non-regular shall be terminated without just causes authorized by the law under Art. 2B2 and Art. 2B3 of the Labor Code. Probationary employees in this case are not entitled to grants enumerated in preceding paragraphs. Department Order No. 3 explicitly prohibits labor-only contracting, defined to be a type of employment wherein: “the contractor or subcontractor recruits, supplies or places workers to perform a job, work or service for a principal, the following elements are present: The contractor or subcontractor does not have substantial capital or investment to perform the job, work or service under its own account and responsibility.

Contractualization has its roots tracing back to 1974 under the rule of Ferdinand Marcos when Ernesto “Boy” Herrera helped draft Presidential Decree 442. This decree which Marcos passed, would give the provisions and grounds for the contractualization of workers in the Philippines; the Labor Code of 1974 introduced the concept of probationary employment to the Philippines and Under Article 281 it states that "employers are allowed to hire people under a probationary status for up to six months. These 6 months are used as a trial period for the emplo