romikgosai/squad_modified_2 huggingface dataset:
The simplest known circadian clock is that of the prokaryotic cyanobacteria. Recent research has demonstrated that the circadian clock of Synechococcus elongatus can be reconstituted in vitro with just the three proteins (KaiA, KaiB, KaiC) of their central oscillator. This clock has been shown to sustain a 22-hour rhythm over several days upon the addition of ATP. Previous explanations of the prokaryotic circadian timekeeper were dependent upon a DNA transcription/translation feedback mechanism.[citation needed]

Q1: What has the simplest known circadian clock?
A1: prokaryotic cyanobacteria
Q2: With how many proteins can the circadian clock of Synechococcus elongatus are needed to reproduce its effect?
A2: three proteins
Q3: What type of feedback mechanism was previously thought to be needed to sustain the clock?
A3: DNA
Q4: How long a rhythm were researchers able to sustain in the in vitro experiment?
A4: 22-hour
Q5: What were the only proteins necessary to the circadian timekeeper experiment?
A5: KaiA, KaiB, KaiC
The rhythm is linked to the light–dark cycle. Animals, including humans, kept in total darkness for extended periods eventually function with a free-running rhythm. Their sleep cycle is pushed back or forward each "day", depending on whether their "day", their endogenous period, is shorter or longer than 24 hours. The environmental cues that reset the rhythms each day are called zeitgebers (from the German, "time-givers"). Totally blind subterranean mammals (e.g., blind mole rat Spalax sp.) are able to maintain their endogenous clocks in the apparent absence of external stimuli. Although they lack image-forming eyes, their photoreceptors (which detect light) are still functional; they do surface periodically as well.[page needed]

Q1: To what is the circadian rhythm tied?
A1: light–dark cycle
Q2: What conditions will produce a free-running rhythm in humans?
A2: total darkness
Q3: What are the environmental factors that can change the rhythm?
A3: zeitgebers
Q4: What do blind mole rats have in place of vision?
A4: photoreceptors
Melatonin is absent from the system or undetectably low during daytime. Its onset in dim light, dim-light melatonin onset (DLMO), at roughly 21:00 (9 p.m.) can be measured in the blood or the saliva. Its major metabolite can also be measured in morning urine. Both DLMO and the midpoint (in time) of the presence of the hormone in the blood or saliva have been used as circadian markers. However, newer research indicates that the melatonin offset may be the more reliable marker. Benloucif et al. found that melatonin phase markers were more stable and more highly correlated with the timing of sleep than the core temperature minimum. They found that both sleep offset and melatonin offset are more strongly correlated with phase markers than the onset of sleep. In addition, the declining phase of the melatonin levels is more reliable and stable than the termination of melatonin synthesis.

Q1: What chemical is absent or low during daylight?
A1: Melatonin
Q2: When is the melatonin onset?
A2: 9 p.m
Q3: At its onset, what can be measured in blood or saliva?
A3: Melatonin
Q4: The presence of what is a circadian marker?
A4: hormone
Q5: What are the more reliable markers in determining sleep timing?
A5: melatonin phase
For temperature studies, subjects must remain awake but calm and semi-reclined in near darkness while their rectal temperatures are taken continuously. Though variation is great among normal chronotypes, the average human adult's temperature reaches its minimum at about 05:00 (5 a.m.), about two hours before habitual wake time. Baehr et al. found that, in young adults, the daily body temperature minimum occurred at about 04:00 (4 a.m.) for morning types but at about 06:00 (6 a.m.) for evening types. This minimum occurred at approximately the middle of the eight hour sleep period for morning types, but closer to waking in evening types.

Q1: What physical factor must be continuously monitored during temperature studies>
A1: temperatures
Q2: At what time does the average adult human reach his lowest temperature?
A2: 05:00
Q3: How long before wake time is the lowest temperature reached?
A3: two hours
Q4: When does the temperature of morning type young adults reach its lowest?
A4: 04:00
Q5: What is the time of lowest temperature for evening type young adults?
A5: 06:00
In 1896, Patrick and Gilbert observed that during a prolonged period of sleep deprivation, sleepiness increases and decreases with a period of approximately 24 hours. In 1918, J.S. Szymanski showed that animals are capable of maintaining 24-hour activity patterns in the absence of external cues such as light and changes in temperature. In the early 20th century, circadian rhythms were noticed in the rhythmic feeding times of bees. Extensive experiments were done by Auguste Forel, Ingeborg Beling, and Oskar Wahl to see whether this rhythm was due to an endogenous clock.[citation needed] Ron Konopka and Seymour Benzer isolated the first clock mutant in Drosophila in the early 1970s and mapped the "period" gene, the first discovered genetic determinant of behavioral rhythmicity. Joseph Takahashi discovered the first mammalian circadian clock mutation (clockΔ19) using mice in 1994. However, recent studies show that deletion of clock does not lead to a behavioral phenotype (the animals still have normal circadian rhythms), which questions its importance in rhythm generation.

Q1: Who noticed that sleepiness increases and decreases in a 24 hour period?
A1: Patrick and Gilbert
Q2: Who showed the animals could maintain activity in the absence of light and temperature changes?
A2: J.S. Szymanski
Q3: What animals rhythmic feeding times were studied in the early 20th century ?
A3: bees
Q4: What gene did Konopka and Benzer map in the early 1970 s?
A4: "period"
Q5: What mutation did Takahashi discover in 1994?
A5: circadian clock
It is now known that the molecular circadian clock can function within a single cell; i.e., it is cell-autonomous. This was shown by Gene Block in isolated mollusk BRNs.[clarification needed] At the same time, different cells may communicate with each other resulting in a synchronised output of electrical signaling. These may interface with endocrine glands of the brain to result in periodic release of hormones. The receptors for these hormones may be located far across the body and synchronise the peripheral clocks of various organs. Thus, the information of the time of the day as relayed by the eyes travels to the clock in the brain, and, through that, clocks in the rest of the body may be synchronised. This is how the timing of, for example, sleep/wake, body temperature, thirst, and appetite are coordinately controlled by the biological clock.[citation needed]

Q1: Inside of what can the molecular circadian clock operate?
A1: single cell
Q2: By functioning within a single, what is the system?
A2: cell-autonomous
Q3: What section of the brain periodically releases hormones?
A3: endocrine glands
Q4: How are sleep and wake cycles as well as body functions coordinated?
A4: biological clock
Q5: What do body hormone receptors do with the body's organs?
A5: synchronise
Light is the signal by which plants synchronize their internal clocks to their environment and is sensed by a wide variety of photoreceptors. Red and blue light are absorbed through several phytochromes and cryptochromes. One phytochrome, phyA, is the main phytochrome in seedlings grown in the dark but rapidly degrades in light to produce Cry1. Phytochromes B–E are more stable with phyB, the main phytochrome in seedlings grown in the light. The cryptochrome (cry) gene is also a light-sensitive component of the circadian clock and is thought to be involved both as a photoreceptor and as part of the clock's endogenous pacemaker mechanism. Cryptochromes 1–2 (involved in blue–UVA) help to maintain the period length in the clock through a whole range of light conditions.

Q1: What signals plants to synchronize their internal clocks?
A1: Light
Q2: What do plants use to sense light?
A2: photoreceptors
Q3: What receptors absorb red and blue light in plants?
A3: phytochromes and cryptochromes
Q4: Which phytochrome found in seedlings deteriorates with light and growth?
A4: phyA
Q5: What is the main phytochrome found in seedling grown in light?
A5: phyB
Studies by Nathaniel Kleitman in 1938 and by Derk-Jan Dijk and Charles Czeisler in the 1990s put human subjects on enforced 28-hour sleep–wake cycles, in constant dim light and with other time cues suppressed, for over a month. Because normal people cannot entrain to a 28-hour day in dim light if at all,[citation needed] this is referred to as a forced desynchrony protocol. Sleep and wake episodes are uncoupled from the endogenous circadian period of about 24.18 hours and researchers are allowed to assess the effects of circadian phase on aspects of sleep and wakefulness including sleep latency and other functions.[page needed]

Q1: What time cycle did studies in 1938 and 1990s use on humans?
A1: 28-hour
Q2: What conditions were suppressed in the 28 hour wake-sleep cycle studies ?
A2: time cues
Q3: How long did the suppression of time clues study last?
A3: month
Q4: What is this forced type of study called?
A4: forced desynchrony
Q5: When in the cycle do wake-sleep cycles break off from the circadian period?
A5: 24.18 hours
Shift-work or chronic jet-lag have profound consequences on circadian and metabolic events in the body. Animals that are forced to eat during their resting period show increased body mass and altered expression of clock and metabolic genes.[medical citation needed] In humans, shift-work that favors irregular eating times is associated with altered insulin sensitivity and higher body mass. Shift-work also leads to increased metabolic risks for cardio-metabolic syndrome, hypertension, inflammation.

Q1: What effect does jet-lag and shift-work have on the human body?
A1: profound consequences
Q2: Animals that eat during resting periods show what body increase?
A2: body mass
Q3: How does irregular eating during shift-work effect insulin?
A3: insulin sensitivity
Q4: Besides insulin sensitivity, what other effect does shift-work have on the body?
A4: higher body mass
Q5: What type of work can lead to heart, hypertension and inflammation?
A5: Shift-work
Studies conducted on both animals and humans show major bidirectional relationships between the circadian system and abusive drugs. It is indicated that these abusive drugs affect the central circadian pacemaker. Individuals suffering from substance abuse display disrupted rhythms. These disrupted rhythms can increase the risk for substance abuse and relapse. It is possible that genetic and/or environmental disturbances to the normal sleep and wake cycle can increase the susceptibility to addiction.

Q1: What do studies show has a bidirectional relationship with the circadian system?
A1: abusive drugs
Q2: What do abusive drugs effect in the circadian system?
A2: circadian pacemaker
Q3: What do drug abusers show in their circadian processes?
A3: disrupted rhythms
Q4: What can the disrupted circadian system cause?
A4: abuse and relapse
Q5: What can disruption to genetics and environment in the sleep cycle cause?
A5: susceptibility to addiction
What drove circadian rhythms to evolve has been an enigmatic question. Previous hypotheses emphasized that photosensitive proteins and circadian rhythms may have originated together in the earliest cells, with the purpose of protecting replicating DNA from high levels of damaging ultraviolet radiation during the daytime. As a result, replication was relegated to the dark. However, evidence for this is lacking, since the simplest organisms with a circadian rhythm, the cyanobacteria, do the opposite of this - they divide more in the daytime. Recent studies instead highlight the importance of co-evolution of redox proteins with circadian oscillators in all three kingdoms of life following the Great Oxidation Event approximately 2.3 billion years ago. The current view is that circadian changes in environmental oxygen levels and the production of reactive oxygen species (ROS) in the presence of daylight are likely to have driven a need to evolve circadian rhythms to preempt, and therefore counteract, damaging redox reactions on a daily basis.

Q1: What is theorized to have evolved with circadian rhythms?
A1: photosensitive proteins
Q2: What is thought that circadian rhythm evolved to protect?
A2: replicating DNA
Q3: From what did  DNA need to be protected in the earliest cells?
A3: ultraviolet radiation
Q4: One possible reason for the development of the circadian system is the need to counteract what ?
A4: redox reactions
Q5: What environmental event occurred 2.3 million years ago?
A5: Great Oxidation Event
Mutations or deletions of clock gene in mice have demonstrated the importance of body clocks to ensure the proper timing of cellular/metabolic events; clock-mutant mice are hyperphagic and obese, and have altered glucose metabolism. In mice, deletion of the Rev-ErbA alpha clock gene facilitates diet-induced obesity and changes the balance between glucose and lipid utilization predisposing to diabetes. However, it is not clear whether there is a strong association between clock gene polymorphisms in humans and the susceptibility to develop the metabolic syndrome.

Q1: What is the body clock gene in animals necessary to ensure?
A1: cellular/metabolic events
Q2: What do mice without the clock gene become?
A2: hyperphagic and obese
Q3: Beside obesity, how else does the lack of a circadian clock effect   the mice?
A3: glucose metabolism
Q4: How certain is it that these circadian clock  effects are the same in humans?
A4: not clear
Q5: What gene needs to be deleted to cause obesity in mice?
A5: Rev-ErbA alpha clock
The primary circadian "clock" in mammals is located in the suprachiasmatic nucleus (or nuclei) (SCN), a pair of distinct groups of cells located in the hypothalamus. Destruction of the SCN results in the complete absence of a regular sleep–wake rhythm. The SCN receives information about illumination through the eyes. The retina of the eye contains "classical" photoreceptors ("rods" and "cones"), which are used for conventional vision. But the retina also contains specialized ganglion cells that are directly photosensitive, and project directly to the SCN, where they help in the entrainment (synchronization) of this master circadian clock.

Q1: Where is the primary circadian gene located in humans?
A1: suprachiasmatic nucleus
Q2: Where are these cell groups found in humans?
A2: hypothalamus
Q3: What would the loss of the SCN cells cause in the sleep-wake rhythm?
A3: complete absence
Q4: What provides information to the SCN?
A4: eyes
Q5: What special cells in the eyes communicate directly to the SCN cells?
A5: ganglion
Early research into circadian rhythms suggested that most people preferred a day closer to 25 hours when isolated from external stimuli like daylight and timekeeping. However, this research was faulty because it failed to shield the participants from artificial light. Although subjects were shielded from time cues (like clocks) and daylight, the researchers were not aware of the phase-delaying effects of indoor electric lights.[dubious – discuss] The subjects were allowed to turn on light when they were awake and to turn it off when they wanted to sleep. Electric light in the evening delayed their circadian phase.[citation needed] A more stringent study conducted in 1999 by Harvard University estimated the natural human rhythm to be closer to 24 hours, 11 minutes: much closer to the solar day but still not perfectly in sync.

Q1: What did early research show people preferred as a day length?
A1: 25 hours
Q2: What was the fault not considered in the early theories of day length?
A2: artificial light
Q3: What did electric lighting in the evening do to the test subjects circadian phase?
A3: delayed
Q4: To what is the 24 hours, 11 minutes day outcome of research closest ?
A4: solar day
Q5: When did more stringent testing determine that humans preferred a 24 hour day?
A5: 1999
More-or-less independent circadian rhythms are found in many organs and cells in the body outside the suprachiasmatic nuclei (SCN), the "master clock". These clocks, called peripheral oscillators, are found in the adrenal gland,[citation needed] oesophagus, lungs, liver, pancreas, spleen, thymus, and skin.[citation needed] Though oscillators in the skin respond to light, a systemic influence has not been proven. There is also some evidence that the olfactory bulb and prostate may experience oscillations when cultured, suggesting that these structures may also be weak oscillators.[citation needed]

Q1: Where else beside the SCN cells are independent circadian rhythms also found?
A1: organs and cells
Q2: What is the term for the independent clocks?
A2: peripheral oscillators
Q3: What is the SCN considered to be in comparison to the peripheral oscillators?
A3: master clock
Q4: In what body gland are the peripheral oscillators located?
A4: adrenal gland
Q5: To what do oscillators in the skin respond?
A5: light
Elizabeth's many historic visits and meetings include a state visit to the Republic of Ireland and reciprocal visits to and from the Pope. She has seen major constitutional changes, such as devolution in the United Kingdom, Canadian patriation, and the decolonisation of Africa. She has also reigned through various wars and conflicts involving many of her realms. She is the world's oldest reigning monarch as well as Britain's longest-lived. In 2015, she surpassed the reign of her great-great-grandmother, Queen Victoria, to become the longest-reigning British head of state and the longest-reigning queen regnant in world history.

Q1: Who is the world's oldest reigning monarch?
A1: Elizabeth
Q2: Than which queen has Elizabeth ruled longer?
A2: Queen Victoria
Q3: How is Victoria related to Elizabeth?
A3: great-great-grandmother
Q4: In what year did Elizabeth pass Victoria's length of rule?
A4: 2015
Q5: In the history of what is Elizabeth the longest reigning queen?
A5: world history
During the war, plans were drawn up to quell Welsh nationalism by affiliating Elizabeth more closely with Wales. Proposals, such as appointing her Constable of Caernarfon Castle or a patron of Urdd Gobaith Cymru (the Welsh League of Youth), were abandoned for various reasons, which included a fear of associating Elizabeth with conscientious objectors in the Urdd, at a time when Britain was at war. Welsh politicians suggested that she be made Princess of Wales on her 18th birthday. Home Secretary, Herbert Morrison supported the idea, but the King rejected it because he felt such a title belonged solely to the wife of a Prince of Wales and the Prince of Wales had always been the heir apparent. In 1946, she was inducted into the Welsh Gorsedd of Bards at the National Eisteddfod of Wales.

Q1: Who did England propose to affiliate with Wales to quell Welsh nationalism?
A1: Elizabeth
Q2: Why did Britain not want Elizabeth to associate with conscientious objectors?
A2: Britain was at war
Q3: What did Elizabeth join in 1946?
A3: Welsh Gorsedd of Bards
Q4: Who was the always the Prince of Wales?
A4: heir apparent
Q5: Who wanted to name Elizabeth Princess of Wales?
A5: Herbert Morrison
Elizabeth and Philip were married on 20 November 1947 at Westminster Abbey. They received 2500 wedding gifts from around the world. Because Britain had not yet completely recovered from the devastation of the war, Elizabeth required ration coupons to buy the material for her gown, which was designed by Norman Hartnell. In post-war Britain, it was not acceptable for the Duke of Edinburgh's German relations, including his three surviving sisters, to be invited to the wedding. The Duke of Windsor, formerly King Edward VIII, was not invited either.

Q1: When were Elizabeth and Philip married?
A1: 20 November 1947
Q2: At what famous cathedral was Elizabeth married?
A2: Westminster Abbey
Q3: How many wedding gifts did Elizabeth and Philip receive?
A3: 2500
Q4: Who designed Elizabeth's wedding gown?
A4: Norman Hartnell
Q5: What former King was not invited to the wedding?
A5: Duke of Windsor
Amid preparations for the coronation, Princess Margaret informed her sister that she wished to marry Peter Townsend, a divorcé‚ 16 years Margaret's senior, with two sons from his previous marriage. The Queen asked them to wait for a year; in the words of Martin Charteris, "the Queen was naturally sympathetic towards the Princess, but I think she thought—she hoped—given time, the affair would peter out." Senior politicians were against the match and the Church of England did not permit remarriage after divorce. If Margaret had contracted a civil marriage, she would have been expected to renounce her right of succession. Eventually, she decided to abandon her plans with Townsend. In 1960, she married Antony Armstrong-Jones, who was created Earl of Snowdon the following year. They divorced in 1978; she did not remarry.

Q1: Who did Princess Margaret want to marry?
A1: Peter Townsend
Q2: What did Queen Elizabeth ask Margaret to do instead of marring Townsend?
A2: wait for a year
Q3: What act would the Church of England not permit?
A3: remarriage after divorce
Q4: Who did Princess Margaret marry in 1960?
A4: Antony Armstrong-Jones
Q5: What title was Armstrong-Jones given?
A5: Earl of Snowdon
The Suez crisis and the choice of Eden's successor led in 1957 to the first major personal criticism of the Queen. In a magazine, which he owned and edited, Lord Altrincham accused her of being "out of touch". Altrincham was denounced by public figures and slapped by a member of the public appalled by his comments. Six years later, in 1963, Macmillan resigned and advised the Queen to appoint the Earl of Home as prime minister, advice that she followed. The Queen again came under criticism for appointing the prime minister on the advice of a small number of ministers or a single minister. In 1965, the Conservatives adopted a formal mechanism for electing a leader, thus relieving her of involvement.

Q1: Aside from her choice of Eden's successor, what crisis caused Elizabeth to be criticized?
A1: Suez crisis
Q2: What did Lord Altrincham accuse Elizabeth of being?
A2: out of touch
Q3: When did Macmillan resign?
A3: 1963
Q4: Who did Elizabeth appoint as Prime Minister after the resignation of Macmillan?
A4: Earl of Home
Q5: When was a formal mechanism for electing the Minister adopted?
A5: 1965
A year later, at the height of the 1975 Australian constitutional crisis, the Australian Prime Minister, Gough Whitlam, was dismissed from his post by Governor-General Sir John Kerr, after the Opposition-controlled Senate rejected Whitlam's budget proposals. As Whitlam had a majority in the House of Representatives, Speaker Gordon Scholes appealed to the Queen to reverse Kerr's decision. She declined, stating that she would not interfere in decisions reserved by the Constitution of Australia for the governor-general. The crisis fuelled Australian republicanism.

Q1: During the Australian constitutional crisis, what Prime Minister was dismissed?
A1: Gough Whitlam
Q2: Who dismissed Whilam from the post of Australian Prime Minister?
A2: Governor-General Sir John Kerr
Q3: Who appealed to Elizabeth to reverse the dismissal of Whitlam?
A3: Speaker Gordon Scholes
Q4: What did Whitlam have in the House of Representatives?
A4: a majority
Q5: What did Elizabeth decline to do in response to the appeal by Scholes?
A5: interfere