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#### Annotation 5731096071436

 #biology #neurology #sleep There are true hardcore DSPS cases with some psychiatric overtones or other health issues that might be particularly intractable, however, those should form a rare minority in the ever-increasing mass of people struggling with DSPS. That mass now includes a countless population of insomniacs who have never heard of DSPS and never even arrived to the problem of phase shift due to the employment of the alarm clock. Weitzman hypothesized that a significant number of patients with sleep onset insomnia might be suffering from undiagnosed DSPS (Weitzman et al. 1981[35]). Now we know that hypothesis certainly holds true, which can be demonstrated by letting insomniacs free run their sleep. A significant phase delay may be observed within the first few days of such a release from the restrictions on the timing of sleep. At the same time, there is an accompanying and nearly instant disappearance of sleep-onset insomnia. ... rare minority of people have pathological DSPS. much of insomnia might be DSPS in disguise: Phase shift simply doesn't occur due to alarm clocks. When these "insomniacs" free run sleep, insomnia disappears, but phase shifts occur.

Good sleep, good learning, good life
w, which is a derivative of free running sleep with some limitations targetted at preventing a phase delay. The presented algorithm fails primarily because of one issue: violation of the rules! <span>There are true hardcore DSPS cases with some psychiatric overtones or other health issues that might be particularly intractable, however, those should form a rare minority in the ever-increasing mass of people struggling with DSPS. That mass now includes a countless population of insomniacs who have never heard of DSPS and never even arrived to the problem of phase shift due to the employment of the alarm clock. Weitzman hypothesized that a significant number of patients with sleep onset insomnia might be suffering from undiagnosed DSPS (Weitzman et al. 1981[35]). Now we know that hypothesis certainly holds true, which can be demonstrated by letting insomniacs free run their sleep. A significant phase delay may be observed within the first few days of such a release from the restrictions on the timing of sleep. At the same time, there is an accompanying and nearly instant disappearance of sleep-onset insomnia. Implausible solutions People who suffer from DSPS often resort to their own implausible solutions that include: (poorly managed) free running sleep with an inevitable phase delays that

#### Annotation 5731303689484

 in real analysis, a branch of mathematics, a slowly varying function is a function of a real variable whose behaviour at infinity is in some sense similar to the behaviour of a function converging at infinity. Similarly, a regularly varying function is a function of a real variable whose behaviour at infinity is similar to the behaviour of a power law function (like a polynomial) near infinity. ... this makes sense now: ln(x) "converges" at infinity, i.e. if x = infinity, the function doesn't grow anymore! This is bc to increase value of ln(x) by constant, you'd e.g. need to double x - in this sense it has converged. regularly varying functions behave like power law functions because if you scale input argument, the function grows by a function of the scale (as opposed to e.g. exponentials, where scaling input scales output by the output - hence exponential: growth depends on itself)

Slowly varying function - Wikipedia

#### Annotation 5731759820044

 This concept is often contrasted with uniform convergence. To say that $$\lim_{n\rightarrow\infty}f_n=f\ \mbox{uniformly}$$ means that $${\displaystyle \lim _{n\rightarrow \infty }\,\sup\{\,\left|f_{n}(x)-f(x)\right|:x\in A\,\}=0,}$$ where $$A$$ is the common domain of $$f$$ and $$f_{n}$$. That is a stronger statement than the assertion of pointwise convergence: every uniformly convergent sequence is pointwise convergent, to the same limiting function, but some pointwise convergent sequences are not uniformly convergent. For example, if $${\displaystyle f_{n}:[0,1)\rightarrow [0,1)}$$ is a sequence of functions defined by $$f_{n}(x)=x^{n}$$, then $${\displaystyle \lim _{n\rightarrow \infty }f_{n}(x)=0}$$ pointwise on the interval [0,1), but not uniformly. ... i've missed some intuition first time around: in closed domain, pointwise = uniform convergence (because sup = max, and this max x needs to converge by pointwise criteria as well). For pointwise, every "point" x, the function family f_n approaches f. Can imagine this as one function slowly creeping towards the other one. The speed of convergence doesn't matter. For uniform it's somewhat different: For open intervals, there might be a supremum that doesn't converge, while all xs converge (i.e. we have pointwise, but not uniform convergence). This means for some given n, the functions have nearly approached each other, but towards boundary of domain, we can always find an x that still hasn't approached f. It refuses to approach, so to speak. It's probably called "uniform convergence" because if it holds, then all x's (even the ones at boundary) converge uniformly - as opposed to example before, where we could find f_n(x)'s at domain boundary that stayed far away from f.

Pointwise convergence - Wikipedia
\lim _{n\rightarrow \infty }f_{n}(x)=f(x)} for every x in the domain. The function f {\displaystyle f} is said to be the pointwise limit function of f n {\displaystyle f_{n}} . Properties <span>This concept is often contrasted with uniform convergence. To say that lim n → ∞ f n = f uniformly {\displaystyle \lim _{n\rightarrow \infty }f_{n}=f\ {\mbox{uniformly}}} means that lim n → ∞ sup { | f n ( x ) − f ( x ) | : x ∈ A } = 0 , {\displaystyle \lim _{n\rightarrow \infty }\,\sup\{\,\left|f_{n}(x)-f(x)\right|:x\in A\,\}=0,} where A {\displaystyle A} is the common domain of f {\displaystyle f} and f n {\displaystyle f_{n}} . That is a stronger statement than the assertion of pointwise convergence: every uniformly convergent sequence is pointwise convergent, to the same limiting function, but some pointwise convergent sequences are not uniformly convergent. For example, if f n : [ 0 , 1 ) → [ 0 , 1 ) {\displaystyle f_{n}:[0,1)\rightarrow [0,1)} is a sequence of functions defined by f n ( x ) = x n {\displaystyle f_{n}(x)=x^{n}} , then lim n → ∞ f n ( x ) = 0 {\displaystyle \lim _{n\rightarrow \infty }f_{n}(x)=0} pointwise on the interval [0,1), but not uniformly. The pointwise limit of a sequence of continuous functions may be a discontinuous function, but only if the convergence is not uniform. For example, f ( x ) = lim n → ∞ cos ⁡ ( π x ) 2 n

#### Flashcard 5731800714508

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#biology #neurology #sleep
Question
theory: old people sleep less due to learning less. Supporting fact?
sleep drops less for active elderly

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for sleep be associated with the amount of learning on the preceding days. This link may also explain a decreased demand for sleep in retirement due to a decrease in intellectual activity. This <span>age-related drop in the demand for sleep is less likely to be observed in highly active individuals. For similar reasons, the entrainment failure can often be found among students during exams. It is not clear how much of this failure can be attributed to stress, or to the desire to d

#### Original toplevel document

Good sleep, good learning, good life
ivity to light zeitgeber) increased demand for sleep (e.g. as a result of intense learning, highly creative job position, exercise, etc.) stress endocrine disorders sleep disorders adolescence <span>A great deal of sleep disorders can be explained by entrainment failure (i.e. the failure to reset the 25-hour circadian rhythm to the 24-hour daylight cycle). In other words, in the interdependence between sleep disorders and entrainment failure, the cause-effect relationship will often be reversed! Due to the physiological function of sleep, which is the rewiring of the neural networks of the brain, we can naturally expect that the demand for sleep be associated with the amount of learning on the preceding days. This link may also explain a decreased demand for sleep in retirement due to a decrease in intellectual activity. This age-related drop in the demand for sleep is less likely to be observed in highly active individuals. For similar reasons, the entrainment failure can often be found among students during exams. It is not clear how much of this failure can be attributed to stress, or to the desire to do more on a given day, or to the actual increase in the demand for sleep. Formula for good sleep There is a little-publicized formula that acts as a perfect cure for people who experience continual or seasonal problems with sleep entrainment. This formula is

#### Flashcard 5731804908812

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#biology #neurology #sleep
Question
USA: % of truck accidents due to drowsiness?
40%

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ductivity at work. For this, the National Commission on Sleep Disorders estimates that sleep deprivation costs $150 billion a year in higher stress and reduced workplace productivity[1]. 40% of <span>truck accidents are attributable to fatigue and drowsiness, and there is an 800% increase in single vehicle commercial truck accidents between midnight and 8 am. Major industrial disasters have been attributed to sleep deprivation (Mitler et al #### Original toplevel document Good sleep, good learning, good life ift after over a year of campaigning for president, he answered without hesitation: 8 hours of sleep. The bad example of disrespect for sleep comes from the most important people in the nation! <span>Yet some dramatic facts related to sleep deprivation have slowly come into light. Each year sleep disorders add$16 billion to national health-care costs (e.g. by contributing to high blood pressure and heart disease). That does not include accidents and lost productivity at work. For this, the National Commission on Sleep Disorders estimates that sleep deprivation costs $150 billion a year in higher stress and reduced workplace productivity[1]. 40% of truck accidents are attributable to fatigue and drowsiness, and there is an 800% increase in single vehicle commercial truck accidents between midnight and 8 am. Major industrial disasters have been attributed to sleep deprivation (Mitler et al. 1988[2])(incl. Three Mile Island, Chernobyl, the gas leak at Bhopal, Zeebrugge disaster, and the Exxon Valdez oil spill). It has been known since the 1920s that sleep improves recall in learning. However, only at the turn of the millennium, research by Dr Robert Stickgold, Associate Professor of Psychiatry #### Annotation 5731810938124  In macroeconomics, the money supply (or money stock) is the total value of money available in an economy at a point of time. There are several ways to define "money", but standard measures usually include currency in circulation and demand deposits (depositors' easily accessed assets on the books of financial institutions).[1][2] The central bank of each country may use a definition of what constitutes money for its purposes status not read Money supply - Wikipedia Fund governance Economic history[show] Private equity and venture capital Recession Stock market bubble Stock market crash Accounting scandals v t e China M2 money supply vs USA M2 money supply <span>In macroeconomics, the money supply (or money stock) is the total value of money available in an economy at a point of time. There are several ways to define "money", but standard measures usually include currency in circulation and demand deposits (depositors' easily accessed assets on the books of financial institutions).[1][2] The central bank of each country may use a definition of what constitutes money for its purposes. Money supply data is recorded and published, usually by the government or the central bank of the country. Public and private sector analysts monitor changes in the money supply becaus #### Annotation 5731813821708  A transaction account, also called a checking account, chequing account, current account, demand deposit account, or share draft account at credit unions, is a deposit account held at a bank or other financial institution. It is available to the account owner "on demand" and is available for frequent and immediate access by the account owner or to others as the account owner may direct. Access may be in a variety of ways, such as cash withdrawals, use of debit cards, cheques (checks) and electronic transfer. In economic terms, the funds held in a transaction account are regarded as liquid funds. In accounting terms they are considered as cash. status not read Transaction account - Wikipedia ate banking Related topics[show] Financial market (participants) Corporate finance Personal finance Public finance Financial law Financial regulation List of banks Category Commons Portal v t e <span>A transaction account, also called a checking account, chequing account, current account, demand deposit account, or share draft account at credit unions, is a deposit account held at a bank or other financial institution. It is available to the account owner "on demand" and is available for frequent and immediate access by the account owner or to others as the account owner may direct. Access may be in a variety of ways, such as cash withdrawals, use of debit cards, cheques (checks) and electronic transfer. In economic terms, the funds held in a transaction account are regarded as liquid funds. In accounting terms they are considered as cash. Transaction accounts are known by a variety of descriptions, including a current account (British English), chequing account or checking account when held by a bank, share draft account #### Annotation 5731817229580  Demand deposits, or non confidential money are funds held in demand accounts in commercial banks.[1] These account balances are usually considered money and form the greater part of the narrowly defined money supply of a country status not read Demand deposit - Wikipedia ate banking Related topics[show] Financial market (participants) Corporate finance Personal finance Public finance Financial law Financial regulation List of banks Category Commons Portal v t e <span>Demand deposits, or non confidential money are funds held in demand accounts in commercial banks.[1] These account balances are usually considered money and form the greater part of the narrowly defined money supply of a country.[2] Simply put, these would be funds like those held in a checking account. Contents 1 History 2 Money supply 3 See also 4 References History U.S. demand deposits at commercial ba #### Flashcard 5731819326732 Question money supply Answer all money available in an economy status measured difficulty not learned 37% [default] 0 Money supply - Wikipedia nture capital Recession Stock market bubble Stock market crash Accounting scandals v t e China M2 money supply vs USA M2 money supply In macroeconomics, the money supply (or money stock) is the <span>total value of money available in an economy at a point of time. There are several ways to define "money", but standard measures usually include currency in circulation and demand deposits (depositors' easily accessed assets on the books of financia #### Flashcard 5731821686028 Question money supply consists of which parts? Answer money in circulation and in demand accounts status measured difficulty not learned 37% [default] 0 #### Flashcard 5731823521036 Question demand account Answer "normal" bank account where money is available on demand status measured difficulty not learned 37% [default] 0 #### Flashcard 5731825356044 Question demand deposit Answer the funds on a demand account status measured difficulty not learned 37% [default] 0 #### Flashcard 5731827191052 Question what type of account is my bank account Answer demand account (also called transaction account) status measured difficulty not learned 37% [default] 0 #### Annotation 5731829026060  This new money makes up the non-M0 components in the M1-M3 statistics. In short, there are two types of money in a fractional-reserve banking system:[7][8][9] central bank money — obligations of a central bank, including currency and central bank depository accountscommercial bank money — obligations of commercial banks, including checking accounts and savings accounts. In the money supply statistics, central bank money is MB while the commercial bank money is divided up into the M1-M3 components. Generally, the types of commercial bank money that tend to be valued at lower amounts are classified in the narrow category of M1 while the types of commercial bank money that tend to exist in larger amounts are categorized in M2 and M3, with M3 having the largest status not read Money supply - Wikipedia rt of these deposits as mandated bank reserves, the balance is available for the making of further loans by the bank. This process continues multiple times, and is called the multiplier effect. <span>This new money makes up the non-M0 components in the M1-M3 statistics. In short, there are two types of money in a fractional-reserve banking system:[7][8][9] central bank money — obligations of a central bank, including currency and central bank depository accounts commercial bank money — obligations of commercial banks, including checking accounts and savings accounts. In the money supply statistics, central bank money is MB while the commercial bank money is divided up into the M1-M3 components. Generally, the types of commercial bank money that tend to be valued at lower amounts are classified in the narrow category of M1 while the types of commercial bank money that tend to exist in larger amounts are categorized in M2 and M3, with M3 having the largest. In the United States, a bank's reserves consist of U.S. currency held by the bank (also known as "vault cash"[10]) plus the bank's balances in Federal Reserve accounts.[11][12] For thi #### Annotation 5731830598924  Commercial banks play a role in the process of money creation, especially under the fractional-reserve banking system used throughout the world. In this system, money is created whenever a bank gives out a new loan. This is because the loan, when drawn on and spent, mostly finishes up as a deposit in the banking system, which is counted as part of money supply. After putting aside a part of these deposits as mandated bank reserves, the balance is available for the making of further loans by the bank. This process continues multiple times, and is called the multiplier effect. status not read Money supply - Wikipedia cies and possible transition to a cashless society 8 See also 9 References 10 Further reading 11 External links Money creation by commercial banks Main article: Fractional-reserve banking <span>Commercial banks play a role in the process of money creation, especially under the fractional-reserve banking system used throughout the world. In this system, money is created whenever a bank gives out a new loan. This is because the loan, when drawn on and spent, mostly finishes up as a deposit in the banking system, which is counted as part of money supply. After putting aside a part of these deposits as mandated bank reserves, the balance is available for the making of further loans by the bank. This process continues multiple times, and is called the multiplier effect. This new money makes up the non-M0 components in the M1-M3 statistics. In short, there are two types of money in a fractional-reserve banking system:[7][8][9] central bank money — oblig #### Annotation 5731833482508  Fractional-reserve banking, the most common form of banking practised by commercial banks worldwide,[1][2] involves banks accepting deposits from customers and making loans to borrowers while holding in reserve an amount equal to only a fraction of the bank's deposit liabilities.[3] Bank reserves are held as cash in the bank or as balances in the bank's account at a central bank. The country's central bank determines the minimum amount that banks must hold in liquid assets, called the "reserve requirement" or "reserve ratio". Banks usually hold more than this minimum amount, keeping excess reserves. status not read Fractional-reserve banking - Wikipedia andards ISO 31000 Professional certification Fund governance Economic history[show] Private equity and venture capital Recession Stock market bubble Stock market crash Accounting scandals v t e <span>Fractional-reserve banking, the most common form of banking practised by commercial banks worldwide,[1][2] involves banks accepting deposits from customers and making loans to borrowers while holding in reserve an amount equal to only a fraction of the bank's deposit liabilities.[3] Bank reserves are held as cash in the bank or as balances in the bank's account at a central bank. The country's central bank determines the minimum amount that banks must hold in liquid assets, called the "reserve requirement" or "reserve ratio". Banks usually hold more than this minimum amount, keeping excess reserves. Bank deposits are usually of a relatively short-term duration while loans made by banks tend to be longer-term[4] – this requires banks to hold reserves to provide liquidity when deposi #### Annotation 5731836890380  A userscript (or user script) is a program, usually written in JavaScript, for modifying web pages[1] to augment browsing. On desktop browsers such as Firefox, they are enabled by use of a userscript manager browser extension such as Greasemonkey status not read Userscript - Wikipedia Userscript - Wikipedia Userscript From Wikipedia, the free encyclopedia Jump to navigation Jump to search For use of userscripts on Wikipedia, see Wikipedia:User scripts. A userscript (or user script) is a program, usually written in JavaScript, for modifying web pages[1] to augment browsing. On desktop browsers such as Firefox, they are enabled by use of a userscript manager browser extension such as Greasemonkey. The Presto-based Opera-browser-supported userscripts (referred to as User JavaScript[2]) are placed in a designated directory. Userscripts are often referred to as Greasemonkey scripts #### Annotation 5731840298252  When a company deposits cash with a bank, the bank records a liability on its balance sheet, representing the obligation to repay the depositor, usually on demand. ... of course also holds for people depositing cash. status not read Liability (financial accounting) - Wikipedia de issued long-term bonds, notes payables, long-term leases, pension obligations, and long-term product warranties. Liabilities of uncertain value or timing are called provisions. Example <span>When a company deposits cash with a bank, the bank records a liability on its balance sheet, representing the obligation to repay the depositor, usually on demand. Simultaneously, in accordance with the double-entry principle, the bank records the cash, itself, as an asset. The company, on the other hand, upon depositing the cash with the bank, re #### Annotation 5731842395404  In financial accounting, a liability is defined as the future sacrifices of economic benefits that the entity is obliged to make to other entities as a result of past transactions or other past events status not read Liability (financial accounting) - Wikipedia Financial Internal Firms Report People and organizations[show] Accountants Accounting organizations Luca Pacioli Development[show] History Research Positive accounting Sarbanes–Oxley Act v t e <span>In financial accounting, a liability is defined as the future sacrifices of economic benefits that the entity is obliged to make to other entities as a result of past transactions or other past events,[1] the settlement of which may result in the transfer or use of assets, provision of services or other yielding of economic benefits in the future. A liability is defined by the follow #### Flashcard 5731843968268 Question how do commercial banks create money? Answer banks give out loans, they get paid back. This continues multiple times. status measured difficulty not learned 37% [default] 0 Money supply - Wikipedia s Main article: Fractional-reserve banking Commercial banks play a role in the process of money creation, especially under the fractional-reserve banking system used throughout the world. <span>In this system, money is created whenever a bank gives out a new loan. This is because the loan, when drawn on and spent, mostly finishes up as a deposit in the banking system, which is counted as part of money supply. After putting aside a part of these #### Annotation 5731846327564  In finance, equity is ownership of assets that may have debts or other liabilities attached to them. Equity is measured for accounting purposes by subtracting liabilities from the value of an asset. For example, if someone owns a car worth$9,000 and owes $3,000 on the loan used to buy the car, then the difference of$6,000 is equity. Equity can apply to a single asset, such as a car or house, or to an entire business

Equity (finance) - Wikipedia

#### Flashcard 5731863891212

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#biology #neurology #sleep
Question
compare with terrorism: how many lives does sleep deprivation cost
six WTC collapses in a decade, i.e. ~1/2 as much

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. 1550 annual fatalities in the US can be attributed to drowsy driving. That's nearly an equivalent of six WTC collapse tragedies in a decade! Amazingly, as the pain and suffering is diluted in the population, drowsy driving does not nearly make as many headlines as a terrorist attack. At least a third of Americans have falle

#### Original toplevel document

Good sleep, good learning, good life
St. Louis from a dive caused by microsleep. Sleep deprivation has changed the future of nuclear fission and the future of oil exploration. Poor sleep kills as many people on the roads as alcohol<span>. 1550 annual fatalities in the US can be attributed to drowsy driving. That's nearly an equivalent of six WTC collapse tragedies in a decade! Amazingly, as the pain and suffering is diluted in the population, drowsy driving does not nearly make as many headlines as a terrorist attack. At least a third of Americans have fallen asleep behind the wheel at least once! During the shift to DST in spring, car accidents increase by 9%. Sleep deprivation carries an astronomical cost to industrialized societies. There are zillions of hours wasted on unprod

#### Flashcard 5731867036940

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#has-images
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exponentials in log-log-plot

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#### Flashcard 5731871493388

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#biology #neurology #sleep
Question
cyclic component of sleep, about 1 day long

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There are two components of sleepiness that drive you to bed: circadian component - sleepiness comes back to us in cycles which are usually about one day long homeostatic component - sleepiness increases with the length of time we stay awake Only a combination of these two components determines the optimum time for sleep. Most importantly, yo

#### Original toplevel document

Good sleep, good learning, good life
rrational shift-work patterns, sleeping pills, alcohol, caffeine, etc. For a chance to break out from unhealthy sleep habits, you need to understand the two-component model of sleep regulation. <span>There are two components of sleepiness that drive you to bed: circadian component - sleepiness comes back to us in cycles which are usually about one day long homeostatic component - sleepiness increases with the length of time we stay awake Only a combination of these two components determines the optimum time for sleep. Most importantly, you should remember that even strong sleepiness resulting from the homeostatic component may not be sufficient to get good sleep if the timing goes against the greatest sleep propensity determined by the circadian component. Circadian component There are around hundred known body functions that oscillate between maximum and minimum values in a day-long cycle. Because these functions take about a day's time

#### Flashcard 5731873852684

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#biology #neurology #sleep
Question
homeostatic component of sleep
longer awake -> more sleepy

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pan> There are two components of sleepiness that drive you to bed: circadian component - sleepiness comes back to us in cycles which are usually about one day long homeostatic component - sleepiness increases with the length of time we stay awake Only a combination of these two components determines the optimum time for sleep. Most importantly, you should remember that even strong sleepiness resulting from the homeostatic compon

#### Original toplevel document

Good sleep, good learning, good life
rrational shift-work patterns, sleeping pills, alcohol, caffeine, etc. For a chance to break out from unhealthy sleep habits, you need to understand the two-component model of sleep regulation. <span>There are two components of sleepiness that drive you to bed: circadian component - sleepiness comes back to us in cycles which are usually about one day long homeostatic component - sleepiness increases with the length of time we stay awake Only a combination of these two components determines the optimum time for sleep. Most importantly, you should remember that even strong sleepiness resulting from the homeostatic component may not be sufficient to get good sleep if the timing goes against the greatest sleep propensity determined by the circadian component. Circadian component There are around hundred known body functions that oscillate between maximum and minimum values in a day-long cycle. Because these functions take about a day's time

#### Flashcard 5731876211980

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#biology #neurology #sleep
Question
two components of sleep?
• homeostatic

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onent - sleepiness comes back to us in cycles which are usually about one day long homeostatic component - sleepiness increases with the length of time we stay awake Only a combination of these <span>two components determines the optimum time for sleep. Most importantly, you should remember that even strong sleepiness resulting from the homeostatic component may not be sufficient to get good sleep

#### Original toplevel document

Good sleep, good learning, good life
rrational shift-work patterns, sleeping pills, alcohol, caffeine, etc. For a chance to break out from unhealthy sleep habits, you need to understand the two-component model of sleep regulation. <span>There are two components of sleepiness that drive you to bed: circadian component - sleepiness comes back to us in cycles which are usually about one day long homeostatic component - sleepiness increases with the length of time we stay awake Only a combination of these two components determines the optimum time for sleep. Most importantly, you should remember that even strong sleepiness resulting from the homeostatic component may not be sufficient to get good sleep if the timing goes against the greatest sleep propensity determined by the circadian component. Circadian component There are around hundred known body functions that oscillate between maximum and minimum values in a day-long cycle. Because these functions take about a day's time

#### Flashcard 5731883552012

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#biology #neurology #sleep
Question
Evolutionarily, why would "oversleeping" not be as useful as overeating?
we believe sleep is for optimizing neural networks. Therefore, required sleep should be proportional to learning on previous days. No point to overdo it.

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developed a tendency to overeat. This is a protection against periods when food is scarce. Adipose tissue works as a survival kit for bad times. However, considering the function of sleep, the <span>demand for sleep should be somewhat proportional to the amount of new learning received on preceding days <span>

#### Original toplevel document

Good sleep, good learning, good life
of the cycle is possible with self-discipline in adhering to cycle-reset rules such as morning exercise, bright light, sleep protective zone in the evening, etc. Argument 2: Excessive sleeping <span>It is true that people who try to free run their sleep may find themselves sleeping outrageously long in the very beginning. This, however, will not last in a healthy individual as long sleep is a body's counter-reaction to various sleep deficits resulting from sleep deprivation. Unlike it is the case with foods, there does not seem to be any evolutionary advantage to getting extra sleep on days when we can afford to sleep longer. In the course of evolution, we have developed a tendency to overeat. This is a protection against periods when food is scarce. Adipose tissue works as a survival kit for bad times. However, considering the function of sleep, the demand for sleep should be somewhat proportional to the amount of new learning received on preceding days. In ancient times, we did not have exam days as opposed to lazy days. Consequently, the link between learning and demand for sleep is quite weak. The body clock will still make us sleep

#### Annotation 5731887746316

 Histamine increases the permeability of the capillaries to white blood cells and some proteins, to allow them to engage pathogens in the infected tissues

Histamine - Wikipedia
and has a central role as a mediator of itching.[5] As part of an immune response to foreign pathogens, histamine is produced by basophils and by mast cells found in nearby connective tissues. <span>Histamine increases the permeability of the capillaries to white blood cells and some proteins, to allow them to engage pathogens in the infected tissues.[6] It consists of an imidazole ring attached to an ethylamine chain; under physiological conditions, the amino group of the side-chain is protonated. Contents 1 Properties 2 Synthesis

#### Annotation 5731889843468

 Histamine is an organic nitrogenous compound involved in local immune responses, as well as regulating physiological function in the gut and acting as a neurotransmitter for the brain, spinal cord, and uterus.[3][4] Histamine is involved in the inflammatory response and has a central role as a mediator of itching

Histamine - Wikipedia
03AX14 (WHO) V04CG03 (WHO) (phosphate) Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). Y verify (what is YN ?) Infobox references <span>Histamine is an organic nitrogenous compound involved in local immune responses, as well as regulating physiological function in the gut and acting as a neurotransmitter for the brain, spinal cord, and uterus.[3][4] Histamine is involved in the inflammatory response and has a central role as a mediator of itching.[5] As part of an immune response to foreign pathogens, histamine is produced by basophils and by mast cells found in nearby connective tissues. Histamine increases the permeability of

#### Annotation 5731892727052

 A conjugate acid, within the Brønsted–Lowry acid–base theory, is a chemical compound formed by the reception of a proton (H+) by a base—in other words, it is a base with a hydrogen ion added to it, as in the reverse reaction it loses a hydrogen ion. On the other hand, a conjugate base is what is left over after an acid has donated a proton during a chemical reaction. Hence, a conjugate base is a species formed by the removal of a proton from an acid, as in the reverse reaction it is able to gain a hydrogen ion.[1] Because some acids are capable of releasing multiple protons, the conjugate base of an acid may itself be acidic. In summary, this can be represented as the following chemical reaction: Acid + Base ⇌ Conjugate Base + Conjugate Acid

Conjugate acid - Wikipedia
cid Acid types Brønsted–Lowry Lewis Acceptor Mineral Organic Oxide Strong Superacids Weak Solid Base types Brønsted–Lowry Lewis Donor Organic Oxide Strong Superbases Non-nucleophilic Weak v t e <span>A conjugate acid, within the Brønsted–Lowry acid–base theory, is a chemical compound formed by the reception of a proton (H+) by a base—in other words, it is a base with a hydrogen ion added to it, as in the reverse reaction it loses a hydrogen ion. On the other hand, a conjugate base is what is left over after an acid has donated a proton during a chemical reaction. Hence, a conjugate base is a species formed by the removal of a proton from an acid, as in the reverse reaction it is able to gain a hydrogen ion.[1] Because some acids are capable of releasing multiple protons, the conjugate base of an acid may itself be acidic. In summary, this can be represented as the following chemical reaction: Acid + Base ⇌ Conjugate Base + Conjugate Acid Johannes Nicolaus Brønsted (left) and Martin Lowry (right). Johannes Nicolaus Brønsted and Martin Lowry introduced the Brønsted–Lowry theory, which proposed that any compound that can t

#### Annotation 5731896134924

 In chemistry, protonation (or hydronation) is the addition of a proton (or hydron, or hydrogen cation), (H+) to an atom, molecule, or ion, forming the conjugate acid.[1] Some examples include the protonation of water by sulfuric acid: H2SO4 + H2O ⇌ H3O+ + HSO −4

Protonation - Wikipedia

#### Annotation 5731898232076

 Although histamine is small compared to other biological molecules (containing only 17 atoms), it plays an important role in the body. It is known to be involved in 23 different physiological functions. Histamine is known to be involved in many physiological functions because of its chemical properties that allow it to be versatile in binding.

Histamine - Wikipedia
and intestinal epithelium Brain: Produces fast inhibitory postsynaptic potentials Intestinal epithelium: chloride secretion (associated with secretory diarrhea) [12][13] Roles in the body <span>Although histamine is small compared to other biological molecules (containing only 17 atoms), it plays an important role in the body. It is known to be involved in 23 different physiological functions. Histamine is known to be involved in many physiological functions because of its chemical properties that allow it to be versatile in binding. It is Coulombic (able to carry a charge), conformational, and flexible. This allows it to interact and bind more easily.[17] Vasodilation and fall in blood pressure It has been kn

#### Annotation 5731900329228

 It has been known for more than one hundred years that an intravenous injection of histamine causes a fall in the blood pressure

Histamine - Wikipedia
versatile in binding. It is Coulombic (able to carry a charge), conformational, and flexible. This allows it to interact and bind more easily.[17] Vasodilation and fall in blood pressure <span>It has been known for more than one hundred years that an intravenous injection of histamine causes a fall in the blood pressure.[18] The underlying mechanism concerns both vascular hyperpermeability and vasodilation. Histamine binding to endothelial cells causes them to contract, thus increasing vascular leak. I

#### Annotation 5731902426380

 Increased vascular permeability causes fluid to escape from capillaries into the tissues, which leads to the classic symptoms of an allergic reaction: a runny nose and watery eyes

Histamine - Wikipedia
larizing factors and other compounds, resulting in blood vessel dilation.[19] These two mechanisms play a key role in the pathophysiology of anaphylaxis. Effects on nasal mucous membrane  <span>Increased vascular permeability causes fluid to escape from capillaries into the tissues, which leads to the classic symptoms of an allergic reaction: a runny nose and watery eyes. Allergens can bind to IgE-loaded mast cells in the nasal cavity's mucous membranes. This can lead to three clinical responses:[20] sneezing due to histamine-associated sensory neural s

#### Annotation 5731905834252

 It supports a variety of functions including emotion, behavior, motivation, long-term memory, and olfaction.[2] Emotional life is largely housed in the limbic system, and it critically aids the formation of memories

Limbic system - Wikipedia
own as the paleomammalian cortex, is a set of brain structures located on both sides of the thalamus, immediately beneath the medial temporal lobe of the cerebrum primarily in the forebrain.[1] <span>It supports a variety of functions including emotion, behavior, motivation, long-term memory, and olfaction.[2] Emotional life is largely housed in the limbic system, and it critically aids the formation of memories. With a primordial structure, the limbic system is involved in lower order emotional processing of input from sensory systems and consists of the amygdaloid nuclear complex (amygdala),

#### Annotation 5731909242124

 Histaminergic means "working on the histamine system", and histaminic means "related to histamine". A histaminergic agent (or drug) is a chemical which functions to directly modulate the histamine system in the body or brain

Histaminergic - Wikipedia

#### Annotation 5731912649996

 The tuberomammillary nucleus is a histaminergic nucleus located within the posterior third of the hypothalamus.[1] It consists of, largely, histaminergic neurons (i.e., histamine-releasing neurons) and is involved with the control of arousal, learning, memory, sleep and energy balance.[1]

Tuberomammillary nucleus - Wikipedia
t of Hypothalamus Identifiers Latin Nucleus tuberomamillaris Acronym(s) TMN NeuroNames 427 NeuroLex ID birnlex_1271 TA A14.1.08.932 FMA 62335 Anatomical terms of neuroanatomy [edit on Wikidata] <span>The tuberomammillary nucleus is a histaminergic nucleus located within the posterior third of the hypothalamus.[1] It consists of, largely, histaminergic neurons (i.e., histamine-releasing neurons) and is involved with the control of arousal, learning, memory, sleep and energy balance.[1] Histaminergic outputs See also: Neurotransmitter system The tuberomammillary nucleus is the sole source of histamine pathways in the human brain. The densest axonal projections fr

#### Annotation 5731916057868

 The expression of NF-κB, the transcription factor that regulates inflammatory processes, is promoted by the constitutive activity of the H1 receptor as well as by agonists that bind at the receptor.[7] H1-antihistamines have been shown to attenuate NF-κB expression and mitigate certain inflammatory processes in associated cells

Histamine H1 receptor - Wikipedia
ligands in structure-based virtual screening studies.[6] Contents 1 Role in inflammation 2 Neurophysiology 3 See also 4 References 5 Further reading 6 External links Role in inflammation <span>The expression of NF-κB, the transcription factor that regulates inflammatory processes, is promoted by the constitutive activity of the H1 receptor as well as by agonists that bind at the receptor.[7] H1-antihistamines have been shown to attenuate NF-κB expression and mitigate certain inflammatory processes in associated cells.[7] Neurophysiology Histamine H1 receptors are activated by endogenous histamine, which is released by neurons that have their cell bodies in the tuberomammillary nucleus of the h

#### Annotation 5731918155020

 The H1 receptor is a histamine receptor belonging to the family of rhodopsin-like G-protein-coupled receptors. This receptor is activated by the biogenic amine histamine. It is expressed in smooth muscles, on vascular endothelial cells, in the heart, and in the central nervous system.

Histamine H1 receptor - Wikipedia
571 NP_001239572 NP_001304053 NP_001304054 NP_001304055 NP_032311 Location (UCSC) Chr 3: 11.14 – 11.26 Mb Chr 6: 114.4 – 114.48 Mb PubMed search [3] [4] Wikidata View/Edit Human View/Edit Mouse <span>The H1 receptor is a histamine receptor belonging to the family of rhodopsin-like G-protein-coupled receptors. This receptor is activated by the biogenic amine histamine. It is expressed in smooth muscles, on vascular endothelial cells, in the heart, and in the central nervous system. The H1 receptor is linked to an intracellular G-protein (Gq) that activates phospholipase C and the inositol triphosphate (IP3) signalling pathway. Antihistamines, which act on this rec

#### Annotation 5731921038604

 Endothelium is a single layer of squamous endothelial cells that line the interior surface of blood vessels, and lymphatic vessels.[1] The endothelium forms an interface between circulating blood or lymph in the lumen and the rest of the vessel wall. Endothelial cells form the barrier between vessels and tissue and control the flow of substances and fluid into and out of a tissue. Endothelial cells in direct contact with blood are called vascular endothelial cells whereas those in direct contact with lymph are known as lymphatic endothelial cells. Vascular endothelial cells line the entire circulatory system, from the heart to the smallest capillaries. These cells have unique functions that include fluid filtration, such as in the glomerulus of the kidney, blood vessel tone, hemostasis, neutrophil recruitment, and hormone trafficking. Endothelium of the interior surfaces of the heart chambers is called endocardium. An impaired function can lead to serious health issues throughout the body.

Endothelium - Wikipedia
ory system Location Lining of the inner surface of blood vessels and lymphatic vessels Identifiers MeSH D004727 TH H2.00.02.0.02003 FMA 63916 Anatomical terms of microanatomy [edit on Wikidata] <span>Endothelium is a single layer of squamous endothelial cells that line the interior surface of blood vessels, and lymphatic vessels.[1] The endothelium forms an interface between circulating blood or lymph in the lumen and the rest of the vessel wall. Endothelial cells form the barrier between vessels and tissue and control the flow of substances and fluid into and out of a tissue. Endothelial cells in direct contact with blood are called vascular endothelial cells whereas those in direct contact with lymph are known as lymphatic endothelial cells. Vascular endothelial cells line the entire circulatory system, from the heart to the smallest capillaries. These cells have unique functions that include fluid filtration, such as in the glomerulus of the kidney, blood vessel tone, hemostasis, neutrophil recruitment, and hormone trafficking. Endothelium of the interior surfaces of the heart chambers is called endocardium. An impaired function can lead to serious health issues throughout the body. Contents 1 Structure 1.1 Terminology 2 Function 2.1 Blood vessel formation 3 Clinical significance 3.1 Research 4 History 5 See also 6 References 7 External links Structure The en

#### Annotation 5731924446476

 Squamous cells have the appearance of thin, flat plates that can look polygonal when viewed from above.[12] Their name comes from squāma, Latin for "scale" – as on fish or snake skin. The cells fit closely together in tissues, providing a smooth, low-friction surface over which fluids can move easily. The shape of the nucleus usually corresponds to the cell form and helps to identify the type of epithelium. Squamous cells tend to have horizontally flattened, nearly oval-shaped nuclei because of the thin, flattened form of the cell. Squamous epithelium is found lining surfaces such as skin or alveoli in the lung, enabling simple passive diffusion as also found in the alveolar epithelium in the lungs

Epithelium - Wikipedia
s almost exclusively found in the bladder, ureters and urethra.[10] Cell types The basic cell types are squamous, cuboidal, and columnar, classed by their shape. Type Description Squamous <span>Squamous cells have the appearance of thin, flat plates that can look polygonal when viewed from above.[12] Their name comes from squāma, Latin for "scale" – as on fish or snake skin. The cells fit closely together in tissues, providing a smooth, low-friction surface over which fluids can move easily. The shape of the nucleus usually corresponds to the cell form and helps to identify the type of epithelium. Squamous cells tend to have horizontally flattened, nearly oval-shaped nuclei because of the thin, flattened form of the cell. Squamous epithelium is found lining surfaces such as skin or alveoli in the lung, enabling simple passive diffusion as also found in the alveolar epithelium in the lungs. Specialized squamous epithelium also forms the lining of cavities such as in blood vessels (as endothelium), in the pericardium (as mesothelium), and in other body cavities. Cuboidal C

#### Annotation 5731926543628

 The endothelium is a thin layer of single flat (squamous) cells that line the interior surface of blood vessels and lymphatic vessels.[2]

Endothelium - Wikipedia
hout the body. Contents 1 Structure 1.1 Terminology 2 Function 2.1 Blood vessel formation 3 Clinical significance 3.1 Research 4 History 5 See also 6 References 7 External links Structure <span>The endothelium is a thin layer of single flat (squamous) cells that line the interior surface of blood vessels and lymphatic vessels.[2] Endothelium is of mesodermal origin. Both blood and lymphatic capillaries are composed of a single layer of endothelial cells called a monolayer. In straight sections of a blood vessel,

#### Annotation 5731928116492

 The endothelium forms an interface between circulating blood or lymph in the lumen and the rest of the vessel wall. This forms a barrier between vessels and tissues and control the flow of substances and fluid into and out of a tissue. This controls the passage of materials and the transit of white blood cells into and out of the bloodstream. Excessive or prolonged increases in permeability of the endothelium, as in cases of chronic inflammation, may lead to tissue swelling (edema).

Endothelium - Wikipedia
dered the endothelium a specialized epithelial tissue.[6] Function Endothelium lines the inner wall of vessels, shown here. Microscopic view showing endothelium (at top) inside the heart. <span>The endothelium forms an interface between circulating blood or lymph in the lumen and the rest of the vessel wall. This forms a barrier between vessels and tissues and control the flow of substances and fluid into and out of a tissue. This controls the passage of materials and the transit of white blood cells into and out of the bloodstream. Excessive or prolonged increases in permeability of the endothelium, as in cases of chronic inflammation, may lead to tissue swelling (edema). Altered barrier function is also implicated in cancer extravasation.[7] Endothelial cells are involved in many other aspects of vessel function, including: Blood clotting (thrombosis &a

#### Annotation 5731929689356

 Antihistamines, which act on this receptor, are used as anti-allergy drugs

Histamine H1 receptor - Wikipedia
the heart, and in the central nervous system. The H1 receptor is linked to an intracellular G-protein (Gq) that activates phospholipase C and the inositol triphosphate (IP3) signalling pathway. <span>Antihistamines, which act on this receptor, are used as anti-allergy drugs. The crystal structure of the receptor has been determined (shown on the right)[5] and used to discover new histamine H1 receptor ligands in structure-based virtual screening studies.[6

#### Annotation 5731932572940

 In biochemistry and pharmacology, a ligand is a substance that forms a complex with a biomolecule to serve a biological purpose. In protein-ligand binding, the ligand is usually a molecule which produces a signal by binding to a site on a target protein.

Ligand (biochemistry) - Wikipedia
t ligands in biochemistry. For ligands in inorganic chemistry, see Ligand. For other uses, see Ligand (disambiguation). Myoglobin (blue) with its ligand heme (orange) bound. Based on PDB: 1MBO​ <span>In biochemistry and pharmacology, a ligand is a substance that forms a complex with a biomolecule to serve a biological purpose. In protein-ligand binding, the ligand is usually a molecule which produces a signal by binding to a site on a target protein. The binding typically results in a change of conformational isomerism (conformation) of the target protein. In DNA-ligand binding studies, the ligand can be a small molecule, ion,[1] or

#### Annotation 5731935980812

 High concentrations of myoglobin in muscle cells allow organisms to hold their breath for a longer period of time. Diving mammals such as whales and seals have muscles with particularly high abundance of myoglobin

Myoglobin - Wikipedia
][7][8][9] Myoglobin is distantly related to hemoglobin,[8][10] oxygen-binding protein in red blood cells. In humans, myoglobin is only found in the bloodstream after muscle injury.[11][12][13] <span>High concentrations of myoglobin in muscle cells allow organisms to hold their breath for a longer period of time. Diving mammals such as whales and seals have muscles with particularly high abundance of myoglobin.[13] Myoglobin is found in Type I muscle, Type II A, and Type II B, but most texts consider myoglobin not to be found in smooth muscle.[citation needed] Myoglobin was the first protein

#### Annotation 5731938077964

 Myoglobin is distantly related to hemoglobin,[8][10] oxygen-binding protein in red blood cells. In humans, myoglobin is only found in the bloodstream after muscle injury

Myoglobin - Wikipedia
Human View/Edit Mouse Myoglobin (symbol Mb or MB) is an iron- and oxygen-binding protein found in the skeletal muscle tissue of vertebrates in general and in almost all mammals.[5][6][7][8][9] <span>Myoglobin is distantly related to hemoglobin,[8][10] oxygen-binding protein in red blood cells. In humans, myoglobin is only found in the bloodstream after muscle injury.[11][12][13] High concentrations of myoglobin in muscle cells allow organisms to hold their breath for a longer period of time. Diving mammals such as whales and seals have muscles with

#### Annotation 5731939650828

 Myoglobin (symbol Mb or MB) is an iron- and oxygen-binding protein found in the skeletal muscle tissue of vertebrates in general and in almost all mammals

Myoglobin - Wikipedia
40 NP_001369741 NP_001369742 NP_001157519 NP_001157520 NP_038621 Location (UCSC) Chr 22: 35.61 – 35.64 Mb Chr 15: 77.02 – 77.05 Mb PubMed search [3] [4] Wikidata View/Edit Human View/Edit Mouse <span>Myoglobin (symbol Mb or MB) is an iron- and oxygen-binding protein found in the skeletal muscle tissue of vertebrates in general and in almost all mammals.[5][6][7][8][9] Myoglobin is distantly related to hemoglobin,[8][10] oxygen-binding protein in red blood cells. In humans, myoglobin is only found in the bloodstream after muscle injury

#### Annotation 5731941223692

 Myoglobin was the first protein to have its three-dimensional structure revealed by X-ray crystallography.[14] This achievement was reported in 1958 by John Kendrew and associates

Myoglobin - Wikipedia
particularly high abundance of myoglobin.[13] Myoglobin is found in Type I muscle, Type II A, and Type II B, but most texts consider myoglobin not to be found in smooth muscle.[citation needed] <span>Myoglobin was the first protein to have its three-dimensional structure revealed by X-ray crystallography.[14] This achievement was reported in 1958 by John Kendrew and associates.[15] For this discovery, Kendrew shared the 1962 Nobel Prize in chemistry with Max Perutz.[16] Despite being one of the most studied proteins in biology, its physiological function is n

#### Annotation 5731942796556

 Myoglobin contains hemes, pigments responsible for the colour of red meat. The colour that meat takes is partly determined by the degree of oxidation of the myoglobin. In fresh meat the iron atom is in the ferrous (+2) oxidation state bound to an oxygen molecule (O2). Meat cooked well done is brown because the iron atom is now in the ferric (+3) oxidation state, having lost an electron. If meat has been exposed to nitrites, it will remain pink because the iron atom is bound to NO, nitric oxide (true of, e.g., corned beef or cured hams). Grilled meats can also take on a pink "smoke ring" that comes from the iron binding to a molecule of carbon monoxide.[20] Raw meat packed in a carbon monoxide atmosphere also shows this same pink "smoke ring" due to the same principles

Myoglobin - Wikipedia
igher affinity for oxygen than does hemoglobin. This difference is related to its different role: whereas hemoglobin transports oxygen, myoglobin's function is to store oxygen. Meat color <span>Myoglobin contains hemes, pigments responsible for the colour of red meat. The colour that meat takes is partly determined by the degree of oxidation of the myoglobin. In fresh meat the iron atom is in the ferrous (+2) oxidation state bound to an oxygen molecule (O2). Meat cooked well done is brown because the iron atom is now in the ferric (+3) oxidation state, having lost an electron. If meat has been exposed to nitrites, it will remain pink because the iron atom is bound to NO, nitric oxide (true of, e.g., corned beef or cured hams). Grilled meats can also take on a pink "smoke ring" that comes from the iron binding to a molecule of carbon monoxide.[20] Raw meat packed in a carbon monoxide atmosphere also shows this same pink "smoke ring" due to the same principles. Notably, the surface of this raw meat also displays the pink color, which is usually associated in consumers' minds with fresh meat. This artificially induced pink color can persist, r

#### Annotation 5731944369420

 Binding occurs by intermolecular forces, such as ionic bonds, hydrogen bonds and Van der Waals forces. The association or docking is actually reversible through dissociation. Measurably irreversible covalent bonding between a ligand and target molecule is atypical in biological systems. In contrast to the definition of ligand in metalorganic and inorganic chemistry, in biochemistry it is ambiguous whether the ligand generally binds at a metal site, as is the case in hemoglobin. In general, the interpretation of ligand is contextual with regards to what sort of binding has been observed. The etymology stems from ligare, which means 'to bind'.

Ligand (biochemistry) - Wikipedia
a function of charge, hydrophobicity, and molecular structure. The instance of binding occurs over an infinitesimal range of time and space, so the rate constant is usually a very small number. <span>Binding occurs by intermolecular forces, such as ionic bonds, hydrogen bonds and Van der Waals forces. The association or docking is actually reversible through dissociation. Measurably irreversible covalent bonding between a ligand and target molecule is atypical in biological systems. In contrast to the definition of ligand in metalorganic and inorganic chemistry, in biochemistry it is ambiguous whether the ligand generally binds at a metal site, as is the case in hemoglobin. In general, the interpretation of ligand is contextual with regards to what sort of binding has been observed. The etymology stems from ligare, which means 'to bind'. Ligand binding to a receptor protein alters the conformation by affecting the three-dimensional shape orientation. The conformation of a receptor protein composes the functional state.

#### Annotation 5731947253004

 A biogenic substance is a product made by or of life forms. The term encompasses constituents, secretions, and metabolites of plants or animals

Biogenic substance - Wikipedia
ced material may be challenged and removed. Find sources: "Biogenic substance" – news · newspapers · books · scholar · JSTOR (December 2009) (Learn how and when to remove this template message) <span>A biogenic substance is a product made by or of life forms. The term encompasses constituents, secretions, and metabolites of plants or animals.[1] In context of molecular biology, biogenic substances are referred to as biomolecules. Contents 1 Examples 2 Abiogenic (opposite) 3 See also 4 References Examples Coal and oil

#### Annotation 5731950660876

 A connection table is in essence a graph containing the complete and explicit description of molecular topology and forms an easily analyzable repository of 2D chemical data for VS. Graph theory forms the mathematical model at the core of topology description, 12–15 and many of the key concepts of molecular graph theory are highlighted in Figure 1 .

Unknown title
xandyatom coordinates based on bond lengths (zcoordinates can be added when three-dimensional (3D) datais to be stored) together with associated atom type, chirality, and bond connection data.11<span>A connection table is inessence a graph containing the complete and explicit description of molecular topology and forms an easily analyzablerepository of 2D chemical data for VS. Graph theory forms the mathematical model at the core of topologydescription,12–15and many of the key concepts of molecular graph theory are highlighted inFigure 1. SD files andother extended connection table formats (e.g., mol2 files16) provide a perfectly usable means of structure datatransport. Their inflexible format requirements and somewhat i

#### Annotation 5731954068748

 Virtual screening techniques have become an increasingly important tool for lead discovery. Whether used in conjunction with HTS or stand alone, VS techniques provide a quick and economical method for the discovery of novel actives

Virtual Screening - an overview | ScienceDirect Topics

#### Annotation 5731956165900

 VS is a computational technique which uses computer programs to search potential hits from virtual fragment libraries. 47 , 48 There are two widely used approaches for VS: Structure-based methods (docking) and ligand-based methods. 49 In contrast to experimental methods, VS, on the one hand, is fast and cost-effective, but on the other hand, has relatively low accuracy of predictions and rapid accumulation of errors.

Virtual Screening - an overview | ScienceDirect Topics
: https://www.sciencedirect.com/science/article/pii/B008045044X002625 Drug Discovery Technologies H. Chen, ... J. Zhou, in Comprehensive Medicinal Chemistry III, 2017 2.08.2.8 Virtual Screening <span>VS is a computational technique which uses computer programs to search potential hits from virtual fragment libraries.47,48 There are two widely used approaches for VS: Structure-based methods (docking) and ligand-based methods.49 In contrast to experimental methods, VS, on the one hand, is fast and cost-effective, but on the other hand, has relatively low accuracy of predictions and rapid accumulation of errors.50,51 Notably, ZINC as one of the big free databases offers various fragment-like libraries including target-orientated libraries for VS. Read full chapterView PDF Read full chapter URL:

#### Annotation 5731957738764

 The crystal structure of the receptor has been determined and used to discover new histamine H1 receptor ligands in structure-based virtual screening studies [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3228891/] ... virtual screen studies are drug tests (screening), except virtual. Finding new H1 receptor ligands (i.e. things that bind to H1 receptor) is useful because it allows to invent drugs that can dock and thus block H1 receptor (I'm supposing)

Histamine H1 receptor - Wikipedia
n intracellular G-protein (Gq) that activates phospholipase C and the inositol triphosphate (IP3) signalling pathway. Antihistamines, which act on this receptor, are used as anti-allergy drugs. <span>The crystal structure of the receptor has been determined (shown on the right)[5] and used to discover new histamine H1 receptor ligands in structure-based virtual screening studies.[6] Contents 1 Role in inflammation 2 Neurophysiology 3 See also 4 References 5 Further reading 6 External links Role in inflammation The expression of NF-κB, the transcription fa

#### Annotation 5731960622348

 The optimized in silico screening approach was successfully applied to identify a chemically diverse set of novel fragment-like (≤ 22 heavy atoms) H1R ligands with an exceptionally high hit rate of 73%.

Crystal structure-based virtual screening for novel fragment-like ligands of the human histamine H1 receptor
he recently determined human histamine H1 receptor (H1R) crystal structure. The method combines molecular docking simulations with a protein-ligand interaction fingerprint (IFP) scoring method. <span>The optimized in silico screening approach was successfully applied to identify a chemically diverse set of novel fragment-like (≤ 22 heavy atoms) H1R ligands with an exceptionally high hit rate of 73%. Of the 26 tested fragments, 19 compounds had affinities ranging from 10 μM to 6 nM. The current study shows the potential of in silico screening against GPCR crystal structures to explo

#### Annotation 5731964816652

 Histamine receptors exhibit constitutive activity, so antihistamines can function as either a neutral receptor antagonist or an inverse agonist at histamine receptors

Antihistamine - Wikipedia
the upper gastrointestinal tract, primarily in the stomach. Antihistamines that target the histamine H2-receptor are used to treat gastric acid conditions (e.g., peptic ulcers and acid reflux). <span>Histamine receptors exhibit constitutive activity, so antihistamines can function as either a neutral receptor antagonist or an inverse agonist at histamine receptors.[2][3][4][5] Only a few currently marketed H1-antihistamines are known to function as inverse agonists.[2][5] Contents 1 Medical uses 2 Types 2.1 H1-antihistamines 2.1.1 H1 antagonists/

#### Annotation 5731968224524

 A receptor which is capable of producing a biological response in the absence of a bound ligand is said to display "constitutive activity".

Receptor (biochemistry) - Wikipedia
ogenous GABA. Note that the idea of receptor agonism and antagonism only refers to the interaction between receptors and ligands and not to their biological effects. Constitutive activity <span>A receptor which is capable of producing a biological response in the absence of a bound ligand is said to display "constitutive activity".[9] The constitutive activity of a receptor may be blocked by an inverse agonist. The anti-obesity drugs rimonabant and taranabant are inverse agonists at the cannabinoid CB1 receptor an

#### Annotation 5731971632396

 A receptor antagonist is a type of receptor ligand or drug that blocks or dampens a biological response by binding to and blocking a receptor rather than activating it like an agonist. Antagonist drugs interfere in natural works of receptor protein.[1] They are sometimes called blockers; examples include alpha blockers, beta blockers, and calcium channel blockers. In pharmacology, antagonists have affinity but no efficacy for their cognate receptors, and binding will disrupt the interaction and inhibit the function of an agonist or inverse agonist at receptors.

Receptor antagonist - Wikipedia

#### Annotation 5731975040268

 #has-images Dose response curves of a full agonist, partial agonist, neutral antagonist, and inverse agonist

Inverse agonist - Wikipedia

#### Annotation 5731978710284

 A prerequisite for an inverse agonist response is that the receptor must have a constitutive (also known as intrinsic or basal) level of activity in the absence of any ligand.[3] An agonist increases the activity of a receptor above its basal level, whereas an inverse agonist decreases the activity below the basal level.

Inverse agonist - Wikipedia
gonist or inverse agonist but can block the activity of either.[1] Inverse agonists have opposite actions to those of agonists but the effects of both of these can be blocked by antagonists.[2] <span>A prerequisite for an inverse agonist response is that the receptor must have a constitutive (also known as intrinsic or basal) level of activity in the absence of any ligand.[3] An agonist increases the activity of a receptor above its basal level, whereas an inverse agonist decreases the activity below the basal level. The efficacy of a full agonist is by definition 100%, a neutral antagonist has 0% efficacy, and an inverse agonist has < 0% (i.e., negative) efficacy. Contents 1 Examples 1.1 Ligand

#### Annotation 5731980283148

 A neutral antagonist has no activity in the absence of an agonist or inverse agonist but can block the activity of either

Inverse agonist - Wikipedia
tagonist, and inverse agonist In pharmacology, an inverse agonist is a drug that binds to the same receptor as an agonist but induces a pharmacological response opposite to that of the agonist. <span>A neutral antagonist has no activity in the absence of an agonist or inverse agonist but can block the activity of either.[1] Inverse agonists have opposite actions to those of agonists but the effects of both of these can be blocked by antagonists.[2] A prerequisite for an inverse agonist response is that

#### Annotation 5731983166732

 An agonist is a chemical that binds to a receptor and activates the receptor to produce a biological response. In contrast, an antagonist blocks the action of the agonist, while an inverse agonist causes an action opposite to that of the agonist

Agonist - Wikipedia
For other uses of "Agonist" or "Agonism", see Agonist (disambiguation). For a primary fictional character in a work, see Protagonist and Antagonist. Agonists activating hypothetical receptors. <span>An agonist is a chemical that binds to a receptor and activates the receptor to produce a biological response. In contrast, an antagonist blocks the action of the agonist, while an inverse agonist causes an action opposite to that of the agonist. Contents 1 Etymology 2 Types of agonists 3 Activity 3.1 Potency 3.2 Therapeutic index 4 See also 5 References Etymology From the Greek αγωνιστής (agōnistēs), contestant; champion

#### Annotation 5731985263884

 Typically people take antihistamines as an inexpensive, generic, over-the-counter drug that can provide relief from nasal congestion, sneezing, or hives caused by pollen, dust mites, or animal allergy with few side effects

Antihistamine - Wikipedia
agonist Biological target Histamine receptors • HRH1 • HRH2 • HRH3 • HRH4 External links MeSH D006633 In Wikidata Antihistamines are drugs which treat allergic rhinitis and other allergies.[1] <span>Typically people take antihistamines as an inexpensive, generic, over-the-counter drug that can provide relief from nasal congestion, sneezing, or hives caused by pollen, dust mites, or animal allergy with few side effects.[1] Antihistamines are usually for short-term treatment.[1] Chronic allergies increase the risk of health problems which antihistamines might not treat, including asthma, sinusitis, and

#### Annotation 5731988147468

 #has-images Mechanism of NF-κB action. In this figure, the NF-κB heterodimer consisting of Rel and p50 proteins is used as an example. While in an inactivated state, NF-κB is located in the cytosol complexed with the inhibitory protein IκBα. Through the intermediacy of integral membrane receptors, a variety of extracellular signals can activate the enzyme IκB kinase (IKK). IKK, in turn, phosphorylates the IκBα protein, which results in ubiquitination, dissociation of IκBα from NF-κB, and eventual degradation of IκBα by the proteasome. The activated NF-κB is then translocated into the nucleus where it binds to specific sequences of DNA called response elements (RE). The DNA/NF-κB complex then recruits other proteins such as coactivators and RNA polymerase, which transcribe downstream DNA into mRNA. In turn, mRNA is translated into protein, resulting in a change of cell function

NF-κB - Wikipedia
arch Nuclear transcriptional activator that binds to enhancer elements in many different cell types "NFKB" redirects here. For the airport in Fiji, see List of airports by ICAO code: N § Fiji. <span>Mechanism of NF-κB action. In this figure, the NF-κB heterodimer consisting of Rel and p50 proteins is used as an example. While in an inactivated state, NF-κB is located in the cytosol complexed with the inhibitory protein IκBα. Through the intermediacy of integral membrane receptors, a variety of extracellular signals can activate the enzyme IκB kinase (IKK). IKK, in turn, phosphorylates the IκBα protein, which results in ubiquitination, dissociation of IκBα from NF-κB, and eventual degradation of IκBα by the proteasome. The activated NF-κB is then translocated into the nucleus where it binds to specific sequences of DNA called response elements (RE). The DNA/NF-κB complex then recruits other proteins such as coactivators and RNA polymerase, which transcribe downstream DNA into mRNA. In turn, mRNA is translated into protein, resulting in a change of cell function.[1][2][3][4] Schematic diagram of NF-κB protein structure. There are two structural classes of NF-κB proteins: class I (top) and class II (bottom). Both classes of proteins contain a N-

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 NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) is a protein complex that controls transcription of DNA, cytokine production and cell survival. NF-κB is found in almost all animal cell types and is involved in cellular responses to stimuli such as stress, cytokines, free radicals, heavy metals, ultraviolet irradiation, oxidized LDL, and bacterial or viral antigens.[1][2][3][5][6] NF-κB plays a key role in regulating the immune response to infection. Incorrect regulation of NF-κB has been linked to cancer, inflammatory and autoimmune diseases, septic shock, viral infection, and improper immune development