document_title: Optical microscope

question_text: what are two different types of light microscopes

question_tokens: what are two different types of light microscopes

text: Optical microscope

text: Types[edit]

text: There are two basic types of optical microscopes: simple microscopes and compound microscopes. A simple microscope is one which uses a single lens for magnification, such as a magnifying glass. A compound microscope uses several lenses to enhance the magnification of an object. The vast majority of modern research microscopes are compound microscopes while some cheaper commercial digital microscopes are simple single lens microscopes. Compound microscopes can be further divided into a variety of other types of microscopes which differ in their optical configurations, cost, and intended purposes.

text: Simple microscope[edit]

text: A simple microscope uses a lens or set of lenses to enlarge an object through angular magnification alone, giving the viewer an erect enlarged virtual image.[3][4] The use of a single convex lens or groups of lenses are still found in simple magnification devices such as the magnifying glass, loupes, and eyepieces for telescopes and microscopes.

text: Compound microscope[edit]

text: A compound microscope uses a lens close to the object being viewed to collect light (called the objective lens) which focuses a real image of the object inside the microscope (image 1). That image is then magnified by a second lens or group of lenses (called the eyepiece) that gives the viewer an enlarged inverted virtual image of the object (image 2).[5] The use of a compound objective/eyepiece combination allows for much higher magnification. Common compound microscopes often feature exchangeable objective lenses, allowing the user to quickly adjust the magnification.[5] A compound microscope also enables more advanced illumination setups, such as phase contrast.

text: Other microscope variants[edit]

text: There are many variants of the compound optical microscope design for specialized purposes. Some of these are physical design differences allowing specialization for certain purposes:

text:
Stereo microscope, a low-powered microscope which provides a stereoscopic view of the sample, commonly used for dissection.
Comparison microscope, which has two separate light paths allowing direct comparison of two samples via one image in each eye.
Inverted microscope, for studying samples from below; useful for cell cultures in liquid, or for metallography.
Fiber optic connector inspection microscope, designed for connector end-face inspection

text: Other microscope variants are designed for different illumination techniques:

text:
Petrographic microscope, whose design usually includes a polarizing filter, rotating stage and gypsum plate to facilitate the study of minerals or other crystalline materials whose optical properties can vary with orientation.
Polarizing microscope, similar to the petrographic microscope.
Phase contrast microscope, which applies the phase contrast illumination method.
Epifluorescence microscope, designed for analysis of samples which include fluorophores.
Confocal microscope, a widely used variant of epifluorescent illumination which uses a scanning laser to illuminate a sample for fluorescence.
Student microscope – an often low-power microscope with simplified controls and sometimes low quality optics designed for school use or as a starter instrument for children.[6]
Ultramicroscope, an adapted light microscope that uses light scattering to allow viewing of tiny particles whose diameter is below or near the wavelength of visible light (around 500 nanometers); mostly obsolete since the advent of electron microscopes

text: Digital microscope[edit]

text: A digital microscope is a microscope equipped with a digital camera allowing observation of a sample via a computer. Microscopes can also be partly or wholly computer-controlled with various levels of automation. Digital microscopy allows greater analysis of a microscope image, for example measurements of distances and areas and quantitaton of a fluorescent or histological stain.

text: Low-powered digital microscopes, USB microscopes, are also commercially available. These are essentially webcams with a high-powered macro lens and generally do not use transillumination. The camera attached directly to the USB port of a computer, so that the images are shown directly on the monitor. They offer modest magnifications (up to about 200×) without the need to use eyepieces, and at very low cost. High power illumination is usually provided by an LED source or sources adjacent to the camera lens.

text: Digital microscopy with very low light levels to avoid damage to vulnerable biological samples is available using sensitive photon-counting digital cameras. It has been demonstrated that a light source providing pairs of entangled photons may minimize the risk of damage to the most light-sensitive samples. In this application of ghost imaging to photon-sparse microscopy, the sample is illuminated with infrared photons, each of which is spatially correlated with an entangled partner in the visible band for efficient imaging by a photon-counting camera.[7]

text: History[edit]

text: Invention[edit]

text: The earliest microscopes were single lens magnifying glasses with limited magnification which date at least as far back as the wide spread use of lenses in eyeglasses in the 13th century.[8]

text: Compound microscopes first appeared in Europe around 1620[9][10] including one demonstrated by Cornelis Drebbel in London (around 1621) and one exhibited in Rome in 1624.[11][12][13]

text: The actual inventor of the compound microscope is unknown although many claims have been made over the years. These include a claim 35[14] years after they appeared by Dutch spectacle-maker Johannes Zachariassen that his father, Zacharias Janssen, invented the compound microscope and/or the telescope as early as 1590. Johannes' (some claim dubious)[15][16][17] testimony pushes the invention date so far back that Zacharias would have been a child at the time, leading to speculation that, for Johannes' claim to be true, the compound microscope would have to have been invented by Johannes' grandfather, Hans Martens.[18] Another claim is that Janssen's competitor, Hans Lippershey (who applied for the first telescope patent in 1608) also invented the compound microscope.[19] Other historians point to the Dutch innovator Cornelis Drebbel with his 1621 compound microscope.[11][12][13]

text: Galileo Galilei is also sometimes cited as a compound microscope inventor. After 1610 he found that he could close focus his telescope to view small objects, such as flies, close up[20] and/or could look through the wrong end in reverse to magnify small objects.[21] The only drawback was that his 2 foot long telescope had to be extended out to 6 feet to view objects that close.[22] After seeing the compound microscope built by Drebbel exhibited in Rome in 1624, Galileo built his own improved version.[11][12][13] In 1625 Giovanni Faber coined the name microscope for the compound microscope Galileo submitted to the Accademia dei Lincei in 1624 [23] (Galileo had called it the "occhiolino" or "little eye"). Faber coined the name from the Greek words μικρόν (micron) meaning "small", and σκοπεῖν (skopein) meaning "to look at", a name meant to be analogous with "telescope", another word coined by the Linceans.[24]

text: Christiaan Huygens, another Dutchman, developed a simple 2-lens ocular system in the late 17th century that was achromatically corrected, and therefore a huge step forward in microscope development. The Huygens ocular is still being produced to this day, but suffers from a small field size, and other minor disadvantages.

text: Popularization[edit]

text: Antonie van Leeuwenhoek (1632–1724) is credited with bringing the microscope to the attention of biologists, even though simple magnifying lenses were already being produced in the 16th century. Van Leeuwenhoek's home-made microscopes were simple microscopes, with a single very small, yet strong lens. They were awkward in use, but enabled van Leeuwenhoek to see detailed images. It took about 150 years of optical development before the compound microscope was able to provide the same quality image as van Leeuwenhoek's simple microscopes, due to difficulties in configuring multiple lenses. In the 1850s John Leonard Riddell, Professor of Chemistry at Tulane University, invented the first practical binocular microscope while carrying out one of the earliest and most extensive American microscopic investigations of cholera.[26][27]

text: Lighting techniques[edit]

text: While basic microscope technology and optics have been available for over 400 years it is much more recently that techniques in sample illumination were developed to generate the high quality images seen today.

text: In August 1893 August Köhler developed Köhler illumination. This method of sample illumination gives rise to extremely even lighting and overcomes many limitations of older techniques of sample illumination. Before development of Köhler illumination the image of the light source, for example a lightbulb filament, was always visible in the image of the sample.

text: The Nobel Prize in physics was awarded to Dutch physicist Frits Zernike in 1953 for his development of phase contrast illumination which allows imaging of transparent samples. By using interference rather than absorption of light, extremely transparent samples, such as live mammalian cells, can be imaged without having to use staining techniques. Just two years later, in 1955, Georges Nomarski published the theory for differential interference contrast microscopy, another interference-based imaging technique.

text: Fluorescence microscopy[edit]

text: Modern biological microscopy depends heavily on the development of fluorescent probes for specific structures within a cell. In contrast to normal transilluminated light microscopy, in fluorescence microscopy the sample is illuminated through the objective lens with a narrow set of wavelengths of light. This light interacts with fluorophores in the sample which then emit light of a longer wavelength. It is this emitted light which makes up the image.

text: Since the mid 20th century chemical fluorescent stains, such as DAPI which binds to DNA, have been used to label specific structures within the cell. More recent developments include immunofluorescence, which uses fluorescently labelled antibodies to recognise specific proteins within a sample, and fluorescent proteins like GFP which a live cell can express making it fluorescent.

text: Components[edit]

text: All modern optical microscopes designed for viewing samples by transmitted light share the same basic components of the light path. In addition, the vast majority of microscopes have the same 'structural' components[28] (numbered below according to the image on the right):

text:
Eyepiece (ocular lens) (1)
Objective turret, revolver, or revolving nose piece (to hold multiple objective lenses) (2)
Objective lenses (3)
Focus knobs (to move the stage)

Coarse adjustment (4)
Fine adjustment (5)

Stage (to hold the specimen) (6)
Light source (a light or a mirror) (7)
Diaphragm and condenser (8)
Mechanical stage (9)

text: Eyepiece (ocular lens)[edit]

text: The eyepiece, or ocular lens, is a cylinder containing two or more lenses; its function is to bring the image into focus for the eye. The eyepiece is inserted into the top end of the body tube. Eyepieces are interchangeable and many different eyepieces can be inserted with different degrees of magnification. Typical magnification values for eyepieces include 5×, 10× (the most common), 15X and 20×. In some high performance microscopes, the optical configuration of the objective lens and eyepiece are matched to give the best possible optical performance. This occurs most commonly with apochromatic objectives.

text: Objective turret (revolver or revolving nose piece)[edit]

text: Objective turret, revolver, or revolving nose piece is the part that holds the set of objective lenses. It allows the user to switch between objective lenses.

text: Objective[edit]

text: At the lower end of a typical compound optical microscope, there are one or more objective lenses that collect light from the sample. The objective is usually in a cylinder housing containing a glass single or multi-element compound lens. Typically there will be around three objective lenses screwed into a circular nose piece which may be rotated to select the required objective lens. These arrangements are designed to be parfocal, which means that when one changes from one lens to another on a microscope, the sample stays in focus. Microscope objectives are characterized by two parameters, namely, magnification and numerical aperture. The former typically ranges from 5× to 100× while the latter ranges from 0.14 to 0.7, corresponding to focal lengths of about 40 to 2 mm, respectively. Objective lenses with higher magnifications normally have a higher numerical aperture and a shorter depth of field in the resulting image. Some high performance objective lenses may require matched eyepieces to deliver the best optical performance.

text: Oil immersion objective[edit]

text: Some microscopes make use of oil-immersion objectives or water-immersion objectives for greater resolution at high magnification. These are used with index-matching material such as immersion oil or water and a matched cover slip between the objective lens and the sample. The refractive index of the index-matching material is higher than air allowing the objective lens to have a larger numerical aperture (greater than 1) so that the light is transmitted from the specimen to the outer face of the objective lens with minimal refraction. Numerical apertures as high as 1.6 can be achieved.[29] The larger numerical aperture allows collection of more light making detailed observation of smaller details possible. An oil immersion lens usually has a magnification of 40 to 100×.

text: Focus knobs[edit]

text: Adjustment knobs move the stage up and down with separate adjustment for coarse and fine focusing. The same controls enable the microscope to adjust to specimens of different thickness. In older designs of microscopes, the focus adjustment wheels move the microscope tube up or down relative to the stand and had a fixed stage.

text: Frame[edit]

text: The whole of the optical assembly is traditionally attached to a rigid arm, which in turn is attached to a robust U-shaped foot to provide the necessary rigidity. The arm angle may be adjustable to allow the viewing angle to be adjusted.

text: The frame provides a mounting point for various microscope controls. Normally this will include controls for focusing, typically a large knurled wheel to adjust coarse focus, together with a smaller knurled wheel to control fine focus. Other features may be lamp controls and/or controls for adjusting the condenser.

text: Stage[edit]

text: The stage is a platform below the objective which supports the specimen being viewed. In the center of the stage is a hole through which light passes to illuminate the specimen. The stage usually has arms to hold slides (rectangular glass plates with typical dimensions of 25×75 mm, on which the specimen is mounted).

text: At magnifications higher than 100× moving a slide by hand is not practical. A mechanical stage, typical of medium and higher priced microscopes, allows tiny movements of the slide via control knobs that reposition the sample/slide as desired. If a microscope did not originally have a mechanical stage it may be possible to add one.

text: All stages move up and down for focus. With a mechanical stage slides move on two horizontal axes for positioning the specimen to examine specimen details.

text: Focusing starts at lower magnification in order to center the specimen by the user on the stage. Moving to a higher magnification requires the stage to be moved higher vertically for re-focus at the higher magnification and may also require slight horizontal specimen position adjustment. Horizontal specimen position adjustments are the reason for having a mechanical stage.

text: Due to the difficulty in preparing specimens and mounting them on slides, for children it's best to begin with prepared slides that are centered and focus easily regardless of the focus level used.

text: Light source[edit]

text: Many sources of light can be used. At its simplest, daylight is directed via a mirror. Most microscopes, however, have their own adjustable and controllable light source – often a halogen lamp, although illumination using LEDs and lasers are becoming a more common provision.

text: Condenser[edit]

text: The condenser is a lens designed to focus light from the illumination source onto the sample. The condenser may also include other features, such as a diaphragm and/or filters, to manage the quality and intensity of the illumination. For illumination techniques like dark field, phase contrast and differential interference contrast microscopy additional optical components must be precisely aligned in the light path.

text: Magnification[edit]

text: The actual power or magnification of a compound optical microscope is the product of the powers of the ocular (eyepiece) and the objective lens. The maximum normal magnifications of the ocular and objective are 10× and 100× respectively, giving a final magnification of 1,000×.

text: Magnification and micrographs[edit]

text: When using a camera to capture a micrograph the effective magnification of the image must take into account the size of the image. This is independent of whether it is on a print from a film negative or displayed digitally on a computer screen.

text: In the case of photographic film cameras the calculation is simple; the final magnification is the product of: the objective lens magnification, the camera optics magnification and the enlargement factor of the film print relative to the negative. A typical value of the enlargement factor is around 5× (for the case of 35mm film and a 15x10 cm (6×4 inch) print).

text: In the case of digital cameras the size of the pixels in the CMOS or CCD detector and the size of the pixels on the screen have to be known. The enlargement factor from the detector to the pixels on screen can then be calculated. As with a film camera the final magnification is the product of: the objective lens magnification, the camera optics magnification and the enlargement factor.

text: Operation[edit]

text: The optical components of a modern microscope are very complex and for a microscope to work well, the whole optical path has to be very accurately set up and controlled. Despite this, the basic operating principles of a microscope are quite simple.

text: The objective lens is, at its simplest, a very high-powered magnifying glass, i.e. a lens with a very short focal length. This is brought very close to the specimen being examined so that the light from the specimen comes to a focus about 160 mm inside the microscope tube. This creates an enlarged image of the subject. This image is inverted and can be seen by removing the eyepiece and placing a piece of tracing paper over the end of the tube. By carefully focusing a brightly lit specimen, a highly enlarged image can be seen. It is this real image that is viewed by the eyepiece lens that provides further enlargement.

text: In most microscopes, the eyepiece is a compound lens, with one component lens near the front and one near the back of the eyepiece tube. This forms an air-separated couplet. In many designs, the virtual image comes to a focus between the two lenses of the eyepiece, the first lens bringing the real image to a focus and the second lens enabling the eye to focus on the virtual image.[30]

text: In all microscopes the image is intended to be viewed with the eyes focused at infinity (mind that the position of the eye in the above figure is determined by the eye's focus). Headaches and tired eyes after using a microscope are usually signs that the eye is being forced to focus at a close distance rather than at infinity.

text: Illumination techniques[edit]

text: Many techniques are available which modify the light path to generate an improved contrast image from a sample. Major techniques for generating increased contrast from the sample include cross-polarized light, dark field, phase contrast and differential interference contrast illumination. A recent technique (Sarfus) combines cross-polarized light and specific contrast-enhanced slides for the visualization of nanometric samples.

text:
Four examples of transilumination techniques used to generate contrast in a sample of tissue paper. 1.559 μm/pixel.

Bright field illumination, sample contrast comes from absorbance of light in the sample.

Cross-polarized light illumination, sample contrast comes from rotation of polarized light through the sample.

Dark field illumination, sample contrast comes from light scattered by the sample.

Phase contrast illumination, sample contrast comes from interference of different path lengths of light through the sample.

text: Other techniques[edit]

text: Modern microscopes allow more than just observation of transmitted light image of a sample; there are many techniques which can be used to extract other kinds of data. Most of these require additional equipment in addition to a basic compound microscope.

text:
Reflected light, or incident, illumination (for analysis of surface structures)
Fluorescence microscopy, both:

text:
Epifluorescence microscopy
Confocal microscopy

text:
Microspectroscopy (where a UV-visible spectrophotometer is integrated with an optical microscope)
Ultraviolet microscopy
Near-Infrared microscopy
Multiple transmission microscopy[31] for contrast enhancement and aberration reduction.
Automation (for automatic scanning of a large sample or image capture)

text: Applications[edit]

text: Optical microscopy is used extensively in microelectronics, nanophysics, biotechnology, pharmaceutic research, mineralogy and microbiology.[32]

text: Optical microscopy is used for medical diagnosis, the field being termed histopathology when dealing with tissues, or in smear tests on free cells or tissue fragments.

text: In industrial use, binocular microscopes are common. Aside from applications needing true depth perception, the use of dual eyepieces reduces eye strain associated with long workdays at a microscopy station. In certain applications, long-working-distance or long-focus microscopes[33] are beneficial. An item may need to be examined behind a window, or industrial subjects may be a hazard to the objective. Such optics resemble telescopes with close-focus capabilities.[34][35]

text: Measuring microscopes are used for precision measurement. There are two basic types. One has a reticle graduated to allow measuring distances in the focal plane.[36] The other (and older) type has simple crosshairs and a micrometer mechanism for moving the subject relative to the microscope.[37]

text: Limitations[edit]

text: At very high magnifications with transmitted light, point objects are seen as fuzzy discs surrounded by diffraction rings. These are called Airy disks. The resolving power of a microscope is taken as the ability to distinguish between two closely spaced Airy disks (or, in other words the ability of the microscope to reveal adjacent structural detail as distinct and separate). It is these impacts of diffraction that limit the ability to resolve fine details. The extent and magnitude of the diffraction patterns are affected by both the wavelength of light (λ), the refractive materials used to manufacture the objective lens and the numerical aperture (NA) of the objective lens. There is therefore a finite limit beyond which it is impossible to resolve separate points in the objective field, known as the diffraction limit. Assuming that optical aberrations in the whole optical set-up are negligible, the resolution d, can be stated as:

text: Usually a wavelength of 550 nm is assumed, which corresponds to green light. With air as the external medium, the highest practical NA is 0.95, and with oil, up to 1.5. In practice the lowest value of d obtainable with conventional lenses is about 200 nm. A new type of lens using multiple scattering of light allowed to improve the resolution to below 100 nm.[38]

text: Surpassing the resolution limit[edit]

text: Multiple techniques are available for reaching resolutions higher than the transmitted light limit described above. Holographic techniques, as described by Courjon and Bulabois in 1979, are also capable of breaking this resolution limit, although resolution was restricted in their experimental analysis.[39]

text: Using fluorescent samples more techniques are available. Examples include Vertico SMI, near field scanning optical microscopy which uses evanescent waves, and stimulated emission depletion. In 2005, a microscope capable of detecting a single molecule was described as a teaching tool.[40]

text: Despite significant progress in the last decade, techniques for surpassing the diffraction limit remain limited and specialized.

text: While most techniques focus on increases in lateral resolution there are also some techniques which aim to allow analysis of extremely thin samples. For example, sarfus methods place the thin sample on a contrast-enhancing surface and thereby allows to directly visualize films as thin as 0.3 nanometers.

text: Structured illumination SMI[edit]

text: SMI (spatially modulated illumination microscopy) is a light optical process of the so-called point spread function (PSF) engineering. These are processes which modify the PSF of a microscope in a suitable manner to either increase the optical resolution, to maximize the precision of distance measurements of fluorescent objects that are small relative to the wavelength of the illuminating light, or to extract other structural parameters in the nanometer range.[41][42]

text: Localization microscopy SPDMphymod[edit]

text: SPDM (spectral precision distance microscopy), the basic localization microscopy technology is a light optical process of fluorescence microscopy which allows position, distance and angle measurements on "optically isolated" particles (e.g. molecules) well below the theoretical limit of resolution for light microscopy. "Optically isolated" means that at a given point in time, only a single particle/molecule within a region of a size determined by conventional optical resolution (typically approx. 200–250 nm diameter) is being registered. This is possible when molecules within such a region all carry different spectral markers (e.g. different colors or other usable differences in the light emission of different particles).[43][44][45][46]

text: Many standard fluorescent dyes like GFP, Alexa dyes, Atto dyes, Cy2/Cy3 and fluorescein molecules can be used for localization microscopy, provided certain photo-physical conditions are present. Using this so-called SPDMphymod (physically modifiable fluorophores) technology a single laser wavelength of suitable intensity is sufficient for nanoimaging.[47]

text: 3D super resolution microscopy[edit]

text: 3D super resolution microscopy with standard fluorescent dyes can be achieved by combination of localization microscopy for standard fluorescent dyes SPDMphymod and structured illumination SMI.[48]

text: STED[edit]

text: Stimulated emission depletion is a simple example of how higher resolution surpassing the diffraction limit is possible, but it has major limitations. STED is a fluorescence microscopy technique which uses a combination of light pulses to induce fluorescence in a small sub-population of fluorescent molecules in a sample. Each molecule produces a diffraction-limited spot of light in the image, and the centre of each of these spots corresponds to the location of the molecule. As the number of fluorescing molecules is low the spots of light are unlikely to overlap and therefore can be placed accurately. This process is then repeated many times to generate the image. Stefan Hell of the Max Planck Institute for Biophysical Chemistry was awarded the 10th German Future Prize in 2006 and Nobel Prize for Chemistry in 2014 for his development of the STED microscope and associated methodologies.[49]

text: Alternatives[edit]

text: In order to overcome the limitations set by the diffraction limit of visible light other microscopes have been designed which use other waves.

text:
Atomic force microscope (AFM)
Scanning electron microscope (SEM)
Scanning ion-conductance microscopy (SICM)
Scanning tunneling microscope (STM)
Transmission electron microscopy (TEM)
Ultraviolet microscope
X-ray microscope

text: It is important to note that higher frequency waves have limited interaction with matter, for example soft tissues are relatively transparent to X-rays resulting in distinct sources of contrast and different target applications.

text: The use of electrons and X-rays in place of light allows much higher resolution – the wavelength of the radiation is shorter so the diffraction limit is lower. To make the short-wavelength probe non-destructive, the atomic beam imaging system (atomic nanoscope) has been proposed and widely discussed in the literature, but it is not yet competitive with conventional imaging systems.

text: STM and AFM are scanning probe techniques using a small probe which is scanned over the sample surface. Resolution in these cases is limited by the size of the probe; micromachining techniques can produce probes with tip radii of 5–10 nm.

text: Additionally, methods such as electron or X-ray microscopy use a vacuum or partial vacuum, which limits their use for live and biological samples (with the exception of an environmental scanning electron microscope). The specimen chambers needed for all such instruments also limits sample size, and sample manipulation is more difficult. Color cannot be seen in images made by these methods, so some information is lost. They are however, essential when investigating molecular or atomic effects, such as age hardening in aluminium alloys, or the microstructure of polymers.


document_title: UFC 182

question_text: who won the first fight between jones vs cormier

root

text: UFC 182

text: Background[edit]

text: The event was headlined by a Light Heavyweight Championship bout between the champion at that time, Jon Jones, and top contender Daniel Cormier.[4]

tag: p

text: Jones was initially scheduled to face Alexander Gustafsson in a rematch on September 27, 2014 at UFC 178.[5] However, Gustafsson pulled out of the bout due to a knee injury and was replaced by Daniel Cormier.[6] Subsequently on August 12, Jones pulled out of the bout against Cormier citing a leg injury, which in turn led to the rescheduling of the pairing to this event.[4]

text: A matchup for the Women's Bantamweight Championship between the champion at the time Ronda Rousey and top contender Cat Zingano was briefly attached to this event. However, it was announced in late October that the pairing was delayed and would take place eight weeks later at UFC 184.[7]

text: Danny Castillo was expected to face Rustam Khabilov, but visa issues forced Khabilov out of the fight.[8] He was replaced by Paul Felder, who was originally scheduled to fight at UFC Fight Night: McGregor vs. Siver.[9]

text: Alexis Dufresne missed weight on her first attempt at the weigh ins, weighing in at 138 pounds. She was given additional time to make the bantamweight limit, but made no attempt to cut further. Instead, she was fined 20 percent of her purse, which went to Marion Reneau.[10]

text: UFC 182 became the second longest UFC event behind UFC 136 with a total in-cage fight time of 154 minutes and 56 seconds.[11]

text: On January 6, it was announced that Jones failed a drug test prior to the event. He tested positive for benzoylecgonine, the primary metabolite of cocaine.[12] As benzoylecgonine is not banned out of competition by the World Anti-Doping Agency, the NSAC could not halt Jones from fighting at UFC 182. He was randomly tested on December 4 and the results came back on December 23, the NSAC Executive Director Bob Bennett said. Jones immediately entered rehab,[12] though it was later revealed by his mother that he only spent one night in rehab.[13]

text: On February 10, it was announced that Hector Lombard failed a fight night drug test, testing positive for the anabolic steroid desoxymethyltestosterone. The failed drug test was responsible for the cancellation of his bout against Rory MacDonald at UFC 186.[14] On March 23, Lombard was suspended for one year, fined and had his win over Josh Burkman overturned to a no contest by the NSAC. He was fined his original $53,000 win bonus, plus one-third of the rest of his purse, which included $53,000 in show money. In addition, Lombard also must pass a drug test prior to getting relicensed by the NSAC.[15]

text: Results[edit]

text:
Main Card

Weight class

Method
Round
Time
Notes

Light Heavyweight
Jon Jones (c)
def.
Daniel Cormier
Decision (unanimous) (49–46, 49–46, 49–46)
5
5:00
[a]

Lightweight
Donald Cerrone
def.
Myles Jury
Decision (unanimous) (30–27, 30–27, 30–27)
3
5:00

Middleweight
Brad Tavares
def.
Nate Marquardt
Decision (unanimous) (30–27, 30–27, 30–27)
3
5:00

Flyweight
Kyoji Horiguchi
def.
Louis Gaudinot
Decision (unanimous) (29–28, 30–27, 30–27)
3
5:00

Welterweight
Hector Lombard
vs.
Josh Burkman
No Contest (overturned)
3
5:00
[b]

Preliminary Card (Fox Sports 1)

Lightweight
Paul Felder
def.
Danny Castillo
KO (spinning back fist)
2
2:09

Bantamweight
Cody Garbrandt
def.
Marcus Brimage
TKO (punches)
3
4:50

Heavyweight
Shawn Jordan
def.
Jared Cannonier
KO (punches)
1
2:57

Lightweight
Evan Dunham
def.
Rodrigo Damm
Decision (unanimous) (30–27, 30–27, 30–27)
3
5:00

Preliminary Card (UFC Fight Pass)

Welterweight
Omari Akhmedov
def.
Mats Nilsson
Decision (unanimous) (29–28, 29–28, 29–28)
3
5:00

Catchweight (138 lbs)
Marion Reneau
def.
Alexis Dufresne
Decision (unanimous) (30–26, 30–26, 30–25)
3
5:00

tag: table

text:
Jump up ^ For the UFC Light Heavyweight Championship.
Jump up ^ Originally a unanimous decision (30–27, 30–27, 29–28) victory for Lombard, the result was changed to "No Contest" after Lombard tested positive for desoxymethyltestosterone during a post-fight screening.[15]

tag: ol

text: Bonus awards[edit]

text: The following fighters were awarded $50,000 bonuses:[17]

text:
Fight of the Night: Jon Jones vs. Daniel Cormier
Performance of the Night: Paul Felder and Shawn Jordan

tag: ul

text: Reported payout[edit]

text: The following is the reported payout to the fighters as reported to the Nevada State Athletic Commission. It does not include sponsor money and also does not include the UFC's traditional "fight night" bonuses.[18]

text:
Jon Jones: $500,000 (no win bonus) def. Daniel Cormier: $90,000
Donald Cerrone: $140,000 (includes $70,000 win bonus) def. Myles Jury: $16,000
Brad Tavares: $50,000 (includes $25,000 win bonus) def. Nate Marquardt: $49,000
Kyoji Horiguchi: $40,000 (includes $20,000 win bonus) def. Louis Gaudinot: $10,000
Hector Lombard: $106,000 (includes $53,000 win bonus) def. Josh Burkman: $45,000
Paul Felder: $20,000 (includes $10,000 win bonus) def. Danny Castillo: $36,000
Cody Garbrandt: $16,000 (includes $8,000 win bonus) def. Marcus Brimage: $12,000
Shawn Jordan: $44,000 (includes $22,000 win bonus) def. Jared Cannonier: $8,000
Evan Dunham: $54,000 (includes $27,000 win bonus) def. Rodrigo Damm: $12,000
Omari Akhmedov: $20,000 (includes $10,000 win bonus) def. Mats Nilsson: $8,000
Marion Reneau: $17,600 (includes $8,000 win bonus) def. Alexis Dufresne: $6,400 ^

text: ^ Alexis Dufresne was fined 20 percent of her purse for failing to make the required weight for her fight with Marion Reneau. That money was issued to Reneau, an NSAC official confirmed.[18]


document_title: U.S. history of alcohol minimum purchase age by state

question_text: when did the drinking age raise to 21

question_tokens: when did the drinking age raise to 21

text: The alcohol laws of the United States regarding minimum age for purchase have changed over time.  This history is given in the table below.  Unless otherwise noted, if different alcohol categories have different minimum purchase ages, the age listed below is set at the lowest age given (e.g. if the purchase age is 18 for beer and 21 for wine or spirits, as was the case in several states, the age in the table will read as "18", not "21").  In addition, the purchase age is not necessarily the same as the minimum age for consumption of alcoholic beverages, although they have often been the same.

text:
As one can see in the table below, there has been much volatility in the states' drinking ages since the
repeal of Prohibition in 1933.  Shortly after the ratification of the 21st amendment in December, most states set their purchase ages at 21 since that was the Voting age at the time. Most of these limits remained constant until the early 1970s.  From 1969 to 1976, some 30 states lowered their purchase ages, generally to 18. This was primarily because the voting age was lowered from 21 to 18 in 1971 with the 26th amendment. Many states started to lower their minimum drinking age in response, most of this occurring in 1972 or 1973.[1][2][3] Twelve states kept their purchase ages at 21 since repeal of Prohibition and never changed them.

text: From 1976 to 1983, several states voluntarily raised their purchase ages to 19 (or, less commonly, 20 or 21), in part to combat drunk driving fatalities.[citation needed] In 1984, Congress passed the National Minimum Drinking Age Act, which required states to raise their ages for purchase and public possession to 21 by October 1986 or lose 10% of their federal highway funds. By mid-1988, all 50 states and the District of Columbia had raised their purchase ages to 21 (but not Puerto Rico, Guam, or the Virgin Islands, see Additional Notes below). South Dakota and Wyoming were the final two states to comply with the age 21 mandate. The current drinking age of 21 remains a point of contention among many Americans, because of it being higher than the age of majority (18 in most states) and higher than the drinking ages of most other countries. The National Minimum Drinking Age Act is also seen as a congressional sidestep of the tenth amendment. Although debates have not been highly publicized, a few states have proposed legislation to lower their drinking age,[4] while Guam has raised its drinking age to 21 in July 2010.[5]

text:
State
Pre-Prohibition(prior to 1919)
Post-Prohibition(after 1933)
1970s / 26th Amendment(adopted in 1971)
1980s / Drinking Age Act of 1984
21st century

Alabama

Pre 1881:None1881:21 (none with consent of parent)[6]
21
1975:Lowered to 19[7]
1986:Raised to 21[8]
21  (no one underage is allowed consumption Section 28-1)

Alaska

?
21[7]
1970:Lowered to 19[9]
1984:Raised to 21 with grandfather clause (if born before January 1, 1965)[10][11]
21

Arizona

?
21[11]
1972:Lowered to 19[12][13]
1985:Raised to 21[8]
21

Arkansas

Pre 1925:None[7]1925:21[7]
21
21[14]
21[8]
21

California

Pre 1891:Regulated by municipality/county (common age was 16)[15][16][17]1891:18 (statewide)[18]
1933:21[7]
21
21[8]
21 (except small amounts for religious ceremonies)

Colorado

None[11]
1945:18: for beer21: for wine and liquor[7]
18[19]
Raised to 21 in 1987[8]
21

Connecticut

?
21[11]
1972:Lowered to 18[20]
1982:Raised to 191983:Raised to 201985:Raised to 21[21]
21 (exemptions: (1) a person over age eighteen who is an employee or permit holder under section 30-90a and who possesses alcoholic liquor in the course of such person's employment or business, (2) a minor who possesses alcoholic liquor on the order of a practicing physician, or (3) a minor who possesses alcoholic liquor while accompanied by a parent, guardian or spouse of the minor, who has attained the age of twenty-one. Nothing in this subsection shall be construed to burden a person's exercise of religion under section 3 of article first of the Constitution of the state in violation of subsection (a) of section 52-571b.[22]

Delaware

?
21[11]
1972:Lowered to 20[13]
1984:Raised to 21[8]
21

District of Columbia

?
18: for beer and wine[11]21: for liquor[23][24]
18: for beer and wine[13][24]21: for liquor
1986:Raised to 21 with grandfather clause.[25][26]
21

Florida

?
18[7]
1980:19[27]
1985:Raised to 21 with grandfather clause[27]
21[28]

Georgia

?
21[11]
1972: Lowered to 18[12]
1984:Raised to 19[14]1985:Raised to 20[14]1986:Raised to 21[14]
21

Hawaii

?
21[7]
1972:Lowered to 18[13]
1986:Raised to 21[8]
21

Idaho

?
20: for beer[29][30]21: for wine and liquor[11][31]
1972:Lowered to 19 (all)[13][32]
1987:Raised to 21 in 1987 (Apr 11) with grandfather clause[8][33]
21

Illinois

1872:Age of majority (none with written consent of parent)[34]
pre 1961: Age of majority      1961:  Raised to 21[35]
1973:Lowered to 19: for beer and wine21: for liquor[36]
1980:Raised to 21[37]
21

Indiana

?
Post-1934:21[7]
21[14]
21[8]
21

Iowa

?
21[7]
1972:Lowered to 19 in 1972 (Jul 1)1973:Lowered to 18 in 1973 (Jul 1)1978:Raised to 19 in 1978 (Jul 1)[38]
1986:Raised to 21 in 1986 (Jul 1) with grandfather clause.[14][38]
21

Kansas

?
1949:18: for beer and wine with less than 4% ABV21: for liquor[7]
18: for beer and wine with less than 4% ABV[14]21: for beer and wine with 4% ABV or more[14]21: for liquor[14][19]
1985:Raised to 21[8]
21 (However, anyone under 21 may consume cereal malt beverages with parental supervision on their own property)

Kentucky

?
1938:21[7]
21[14]
21[8]
21

Louisiana

?
As of 1948:18[13]
18[19]
1987:Raised to 21 de jure in 1987,[8]but de facto age was still 18 until 1995 due to a sale loophole.1995:De facto age raised to 21 in 1995 when loophole was closed.[39]1996:In 1996, briefly lowered by Louisiana Supreme Court to 18 until it reversed its decision, raising to 21 three months later.[40]Other exceptions still remain.[41]
21 (Exceptions to state law include:[42]
For an established religious purpose;When a person under twenty-one years of age is accompanied by a parent, spouse, or legal guardian twenty-one years of age or older;For medical purposes when purchased as an over the counter medication, or when prescribed or administered by a licensed physician, pharmacist, dentist, nurse, hospital, or medical institution;In a private residence, which shall include a residential dwelling and up to twenty contiguous acres, on which the dwelling is located, owned by the same person who owns the dwelling;The sale, handling, transport, or service in dispensing of any alcoholic beverage pursuant to lawful ownership of an establishment or to lawful employment of a person under twenty-one years of age by a duly licensed manufacturer, wholesaler, or retailer of beverage alcohol.)

Maine

?
21[7]1969:Lowered to 20
1972:Lowered to 18[12]1977:Raised to 20[8][43]
1985:Raised to 21[8]
21

Maryland

?
21[7]
1974:Lowered to 18: for beer and wine21: for liquor[44][45]
1982:Raised to 21 with grandfather clause[8][46]
21 (however anyone can drink when parents, spouses, teachers are present)

Massachusetts

?
21[11]
1973:Lowered to 181979:Raised to 20 in 1979 (Apr 16)[47][48][49]
Raised to 21 in 1985[8]
21

Michigan

?
21[7]
1972:Lowered to 18 in 1972 (Jan 1)[50]
1978:Raised to 19 in 1978 (Dec 3)[51][52]1978:Raised to 21 in 1978 (Dec 21), 18 days later.[8]First state to raise age to 21 since it was lowered
21

Minnesota

?
21[11]
1973:Lowered to 18 (June 1)1976:Raised to 19 (Sept 1)[53]First state to raise age after lowering.

1986:Raised to 21[54]
21

Mississippi

?
1966:18: for beer and wine21: for liquor[7](alcohol not legalized until 1966)
18[19]
Raised to 21 in 1986[8]
21

Missouri

?
1945:21[7]
21
21[8]
21

Montana

?
21[11]
1971:Lowered to 19[55]1973:Lowered to 18[56][57]1979:Raised to 19
1987:Raised to 21[8][58]
21

Nebraska

?
21[59]1969:Lowered to 20
1972:Lowered to 19[59]
1980:Raised to 20[14]1985:Raised to 21[14]
21

Nevada

?
1933:21[7]
21
21[8]
21

New Hampshire

?
21[11]
1973:Lowered to 18[60]1979:Raised to 20
1985:Raised to 21[8][21]
21

New Jersey

Before 1880:NonePost-1880:18 (penalties only against businesses)[61][62][63]
21[citation needed]
1973:Lowered to 18[12]
1980:Raised to 191983:Raised to 21[8][64]
21

New Mexico

?
1934:21[7]
21[14]
21[8]
21

New York

21
18[65]
18
1982:Raised to 19 in 1982 (Dec)1985:Raised to 21 in 1985 (Dec)[21][66][67]
21

North Carolina

?
18[11]
18: for beer and wine[19] 21: for liquor
1983:19: for beer and wine 21: for liquor1986:Raised to 21 in 1986 (Sep 1)[8][26]
21

North Dakota

?
1936:21[7]
21[14]
21[68]
21

Ohio

?
1935:18: for 3.2% ABW beer21: for beer stronger than 3.2% ABW, wine and liquor[69]
18: for 3.2% ABW beer21: for beer stronger than 3.2% ABW, wine and liquor
1982 (Aug. 19 to Oct. 1):19: for 3.2% ABW beer[14]21: for beer stronger than 3.2% ABW, wine and liquor[14]1982 (From Oct. 1):19: beer21: wine and liquor[70]1988:21[14]
21 (However, anyone can drink with parents or legal-age spouse)

Oklahoma

?
Men:21Women:18: 3.2% ABW beer21: for beer stronger than 3.2% ABW, wine and liquor[71]
1976:Lowered to 18 (for 3.2% ABW beer) for both sexes in 1976 (Dec)[72]Last state to lower the drinking age.
1983:Raised to 21[11][73]
21

Oregon

?
1933:21[7]
21
21[8]
21

Pennsylvania

?
1935:21[7]
21
21[8][52]
21

Rhode Island

?
21[11]
1970:Lowered to 18[12][74]
1980:Raised to 191981:Raised to 201984:Raised to 21[21]
21

South Carolina

21[75]
1935:18: for beer and wine21: for liquor[7]
18: for beer and wine[19]21: for liquor
1984:19: for beer and wine[7]21: for liquor1986:Raised to 21[8]
21

South Dakota

?
1934:21 (all)1939:Lowered to 18: for 3.2% beerRaised to 19: for 3.2% beer[76]
1972:18: for beer and wine21: for liquor[13]
1984:19: for beer and wine21: for liquor[8]1988:Raised to 21[58]
21

Tennessee

Pre 1881:None1881:21[77]
21[7]1964:Lowered to 18[7]
1979:Raised to 19
1984:Raised to 21[8]
21

Texas

Pre 1909:21None (with written permission of parent or guardian)Post 1909:21[78][79]
21[7]
1973:Lowered to 18[80]
1981:Raised to 19[81]1986:Raised to 21 in 1986 (Sep 1)[8][26]
21

Utah

?
1935:21[7]
21[14]
21[8]
21

Vermont

?
21[7]
1971:Lowered to 18[82][83]
1986:Raised to 21[21][83]
21

Virginia

?
21[84]
1974:Lowered to 18: for beer and wine(21: for liquor remained)[84]
1981:Raised to 19 for off-premises consumption1983:Raised to 19 (all beer)1985:Raised to 21[84]
21

Washington

"Age of majority"since 1877[85]
21[citation needed]
21
21[8]
21

West Virginia

?
18: for beer and wine 21: for liquor[11]
1972:Lowered to 18 (all)[86]
1983:Raised to 19(& 21 for non-residents)[8][43]1986:Raised to 21[8]
21

Wisconsin

1839–1866:18: for wine and liquorNone: for beerPost-1866:21 (all)[87]
18: for beer21: for wine and spirits1957:21: for residents of bordering states with age limit 21.[88]1963:Raised to 21 (off-premises beer sales, remained 18 for on-premises).[88]
1972:Lowered to 18 (all) in 1972 (Mar)[88]1977:Border state restriction lifted.[88]
1984:Raised to 191986:Raised to 21 (September 1, 1986)[88]
21 (however anyone can drink when parents, spouses, teachers are present)[citation needed]

Wyoming

?
21[7]
1973:Lowered to 19[13]
1988:Raised to 21 in 1988 (Jul 1)[89][90]Last state to raise de jure drinking age to 21
21

American Samoa

?
?
?
21?
21[91]

Northern Mariana Islands

–
–
?
21?
21[92]

Puerto Rico

?
18
18
Kept at 18despite 10% highway fundingpenalty under Drinking Age Act.
18[93]

Virgin Islands

?
?
?
18
18[94]

Guam

?
21?
18
18
Raised to 21 in 2010[5]

text: Additional notes[edit]

text:
Contrary to popular belief, since the National Minimum Drinking Age Act of 1984, not all states specifically prohibit minors' and young adults' consumption of alcohol in private settings.  That is because the federal law is concerned only with purchase and public possession, not private consumption, and contains several exceptions. As of January 1, 2007, 14 states and the District of Columbia ban underage consumption outright, 19 states do not specifically ban underage consumption outright, and 17 states have family member or location exceptions to their underage consumption laws. Federal law explicitly provides for religious, medical, employment and private club possession exceptions; as of 2005, 31 states have family member or location exceptions to their underage possession laws.[41]
In the 1960s the age for buying or drinking beer and wine in the District of Columbia (Washington, D.C.) was 18; the age for hard liquor was 21.[23][24] Residents from Virginia and Maryland would often drive to D.C. to obtain alcohol. In Louisiana, the 1987 law raising the age from 18 to 21 was deliberately written solely to comply with the National Minimum Drinking Age Act of 1984 to avoid losing highway funding, while still allowing 18- to 20-year-olds to drink as before.  Not only did it still allow 18- to 20-year-olds to consume in private, it contained a major loophole allowing bars and stores to sell alcohol to 18- to 20-year-olds without penalty (despite purchase being technically illegal) which meant that the de facto age was still 18.[39] In other words, the drinking age was 21 only on paper. This loophole was closed in 1995, but in 1996 the Louisiana Supreme Court declared a drinking age of 21 unconstitutional.[39]  That briefly lowered the de jure purchase age to 18, causing an uproar which prompted the Louisiana Supreme Court to reverse its decision, raising the age to 21 three months later.[40] Other exceptions still remain to this day, including drinking in a private residence,[41] and Louisiana still has some of the most liberal general alcohol laws of any state.
Some states were "dry" well before national Prohibition was enacted in 1919, in some cases since achieving statehood.  Also, some states did not become fully "wet" until several years after the repeal of Prohibition in 1933 (e.g. Mississippi in 1966).  Since 1966, all states and territories of the USA have been "wet", but dry counties and towns still exist in some states.


document_title: ATP synthase

question_text: where can you find atp synthase in a plant cell

text: ATP synthase

text: Nomenclature[edit]

text: The F1 fraction derives its name from the term "Fraction 1" and FO (written as a subscript letter "o", not "zero") derives its name from being the binding fraction for oligomycin, a type of naturally-derived antibiotic that is able to inhibit the FO unit of ATP synthase.[3][4] These functional regions consist of different protein subunits — refer to tables.

text: Structure and function[edit]

text:
Located within the thylakoid membrane and the inner mitochondrial membrane, ATP synthase consists of two regions FO and F1. FO causes rotation of F1 and is made of c-ring and subunits a, b, d, F6. F1 is made of

α
,
β
,
γ
,
δ

{\displaystyle \alpha ,\beta ,\gamma ,\delta }

 subunits. F1 has a water-soluble par that can hydrolyze ATP. FO on the other hand has mainly hydrophobic regions. FO F1 creates a pathway for protons movement across the membrane.[7]

text: F1 region[edit]

text:
The F1 portion of ATP synthase is hydrophilic and responsible for hydrolyzing ATP. Subunits

α

{\displaystyle \alpha }

 and

β

{\displaystyle \beta }

 make a hexamer with 6 binding sites. Three of them are catalytically inactive and they bind ADP.

text:
Other three subunits catalyze the ATP synthesis. The other F1 subunits

γ
,
δ
,
ϵ

{\displaystyle \gamma ,\delta ,\epsilon }

 are a part of a rotational motor mechanism.

γ

{\displaystyle \gamma }

 subunit allows

β

{\displaystyle \beta }

 to go though conformational changes, i.e. closed, half open and open states allows for ATP to be bound and released once synthesized. The F1 particle is large and can be seen in the transmission electron microscope by negative staining.[8] These are particles of 9 nm diameter that pepper the inner mitochondrial membrane.

text:
F1 - Subunits

Subunit
Human Gene

alpha
ATP5A1, ATPAF2

beta
ATP5B, ATPAF1, C16orf7

gamma
ATP5C1

delta
ATP5D

epsilon
ATP5E

text: FO region[edit]

text: Fo is a water insoluble protein with eight subunits and a transmembrane ring. The ring has a tetramer shape with a helix loop helix protein that goes though conformational changes when protonated and deprotonated, pushing neighboring subunits to rotate, causing the spinning of FO which then also affects conformation of F1, resulting in switching of states of alpha and beta subunits. The FO region of ATP synthase is a proton pore that is embedded in the mitochondrial membrane. It consists of three main subunits a, b, and c, and (in humans) six additional subunits, d, e, f, g, F6, and 8 (or A6L). An atomic model for the dimeric yeast FO region was determined by cryo-EM at an overall resolution of 3.6 Å [10]

text:
FO-Main subunits

Subunit
Human Gene

a
ATP6

b
ATP5F1

c
ATP5G1, ATP5G2, ATP5G3

text: Binding model[edit]

text: In the 1960s through the 1970s, Paul Boyer, a UCLA Professor, developed the binding change, or flip-flop, mechanism theory, which postulated that ATP synthesis is dependent on a conformational change in ATP synthase generated by rotation of the gamma subunit. The research group of John E. Walker, then at the MRC Laboratory of Molecular Biology in Cambridge, crystallized the F1 catalytic-domain of ATP synthase. The structure, at the time the largest asymmetric protein structure known, indicated that Boyer's rotary-catalysis model was, in essence, correct. For elucidating this, Boyer and Walker shared half of the 1997 Nobel Prize in Chemistry.

text: The crystal structure of the F1 showed alternating alpha and beta subunits (3 of each), arranged like segments of an orange around a rotating asymmetrical gamma subunit. According to the current model of ATP synthesis (known as the alternating catalytic model), the transmembrane potential created by (H+) proton cations supplied by the electron transport chain, drives the (H+) proton cations from the intermembrane space through the membrane via the FO region of ATP synthase. A portion of the FO (the ring of c-subunits) rotates as the protons pass through the membrane. The c-ring is tightly attached to the asymmetric central stalk (consisting primarily of the gamma subunit), causing it to rotate within the alpha3beta3 of F1 causing the 3 catalytic nucleotide binding sites to go through a series of conformational changes that lead to ATP synthesis. The major F1 subunits are prevented from rotating in sympathy with the central stalk rotor by a peripheral stalk that joins the alpha3beta3 to the non-rotating portion of FO. The structure of the intact ATP synthase is currently known at low-resolution from electron cryo-microscopy (cryo-EM) studies of the complex. The cryo-EM model of ATP synthase suggests that the peripheral stalk is a flexible structure that wraps around the complex as it joins F1 to FO. Under the right conditions, the enzyme reaction can also be carried out in reverse, with ATP hydrolysis driving proton pumping across the membrane.

text: The binding change mechanism involves the active site of a β subunit's cycling between three states.[11] In the "loose" state, ADP and phosphate enter the active site; in the adjacent diagram, this is shown in pink. The enzyme then undergoes a change in shape and forces these molecules together, with the active site in the resulting "tight" state (shown in red) binding the newly produced ATP molecule with very high affinity. Finally, the active site cycles back to the open state (orange), releasing ATP and binding more ADP and phosphate, ready for the next cycle of ATP production.[12]

text: Physiological role[edit]

text: Like other enzymes, the activity of F1FO ATP synthase is reversible. Large-enough quantities of ATP cause it to create a transmembrane proton gradient, this is used by fermenting bacteria that do not have an electron transport chain, but rather hydrolyze ATP to make a proton gradient, which they use to drive flagella and the transport of nutrients into the cell.

text: In respiring bacteria under physiological conditions, ATP synthase, in general, runs in the opposite direction, creating ATP while using the proton motive force created by the electron transport chain as a source of energy. The overall process of creating energy in this fashion is termed oxidative phosphorylation. The same process takes place in the mitochondria, where ATP synthase is located in the inner mitochondrial membrane and the F1-part projects into mitochondrial matrix. The consumption of ATP by ATP-synthase pumps proton cations into the matrix.

text: Evolution[edit]

text: The evolution of ATP synthase is thought to have been modular whereby two functionally independent subunits became associated and gained new functionality.[13][14] This association appears to have occurred early in evolutionary history, because essentially the same structure and activity of ATP synthase enzymes are present in all kingdoms of life.[13] The F-ATP synthase displays high functional and mechanistic similarity to the V-ATPase.[15] However, whereas the F-ATP synthase generates ATP by utilising a proton gradient, the V-ATPase generates a proton gradient at the expense of ATP, generating pH values of as low as 1.[16]

text: The F1 region also shows significant similarity to hexameric DNA helicases, and the FO region shows some similarity to H+-powered flagellar motor complexes.[15] The α3β3 hexamer of the F1 region shows significant structural similarity to hexameric DNA helicases; both form a ring with 3-fold rotational symmetry with a central pore. Both have roles dependent on the relative rotation of a macromolecule within the pore; the DNA helicases use the helical shape of DNA to drive their motion along the DNA molecule and to detect supercoiling, whereas the α3β3 hexamer uses the conformational changes through the rotation of the γ subunit to drive an enzymatic reaction.[17]

text: The H+ motor of the FO particle shows great functional similarity to the H+ motors that drive flagella.[15] Both feature a ring of many small alpha-helical proteins that rotate relative to nearby stationary proteins, using a H+ potential gradient as an energy source. This link is tenuous, however, as the overall structure of flagellar motors is far more complex than that of the FO particle and the ring with about 30 rotating proteins is far larger than the 10, 11, or 14 helical proteins in the FO complex.

text: The modular evolution theory for the origin of ATP synthase suggests that two subunits with independent function, a DNA helicase with ATPase activity and a H+ motor, were able to bind, and the rotation of the motor drove the ATPase activity of the helicase in reverse.[13][17] This complex then evolved greater efficiency and eventually developed into today's intricate ATP synthases. Alternatively, the DNA helicase/H+ motor complex may have had H+ pump activity with the ATPase activity of the helicase driving the H+ motor in reverse.[13] This may have evolved to carry out the reverse reaction and act as an ATP synthase.[14][18][19]

text: In different species[edit]

text: E. coli[edit]

text: E. coli ATP synthase is the simplest known form of ATP synthase, with 8 different subunit types.[20]

text: Yeast[edit]

text: Yeast ATP synthase is one of the best-studied eukaryotic ATP synthases; and five F1, eight FO subunits, and seven associated proteins have been identified.[7] Most of these proteins have homologues in other eukaryotes.[21][22][23]

text: Plant[edit]

text: In plants, ATP synthase is also present in chloroplasts (CF1FO-ATP synthase). The enzyme is integrated into thylakoid membrane; the CF1-part sticks into stroma, where dark reactions of photosynthesis (also called the light-independent reactions or the Calvin cycle) and ATP synthesis take place. The overall structure and the catalytic mechanism of the chloroplast ATP synthase are almost the same as those of the mitochondrial enzyme. However, in chloroplasts, the proton motive force is generated not by respiratory electron transport chain but by primary photosynthetic proteins.

text: Bovine[edit]

text: The ATP synthase isolated from bovine heart mitochondria (Bos taurus) is, in terms of biochemistry and structure, the best-characterized ATP synthase. Beef heart is used as a source for the enzyme because of the high concentration of mitochondria in cardiac muscle.[24][25][26]

text: Human[edit]

text: The following is a list of humans genes that encode components of ATP synthases:

text:
ATP5A1, ATP5AL1
ATP5B, ATP5BL1
ATP5C2, ATP5D, ATP5E, ATP5F1, ATP5G1, ATP5G2, ATP5G3, ATP5H, ATP5HP1, ATP5I, ATP5J, ATP5J2, ATP5L, ATP5L2, ATP5O, ATP5S
ATP6, ATP6AP1, ATP6AP2
ATPSBL1, ATPSBL2
MT-ATP6, MT-ATP8


document_title: Midnight

question_text: when does the time change from am to pm

question_tokens: when does the time change from am to pm

text: Midnight

text: Start and end of day[edit]

text: Midnight marks the beginning and ending of each day in civil time throughout the world. It is the dividing point between one day and another. With 12-hour time notation, authorities recommend avoiding confusion between noon and midnight by using "midnight" and to use the notation "11.59 PM" instead of "midnight" in combination with a date, so that it is a clear which day is being referred to.[1]

text: In the United States and Canada, digital clocks and computers commonly display 12 a.m. right at midnight. While that phrase may be used practically, it helps to understand that any particular time is actually an instant. The "a.m." shown on clock displays refers to the 12-hour period following the instant of midnight, not to the instant itself, so that, when a clock displays "12:00 a.m.", (the instant of) midnight has already passed and the period before noon of a new day has begun. In other words, 11:59 p.m. shows until midnight; at the instant of midnight, it changes to 12:00. Simultaneously, the p.m. changes to a.m., though, strictly speaking, a.m. does not apply to the instant of midnight which separates p.m. and a.m. In 24-hour time notation, "0:00" and "0:00:00" refer to midnight at the start of a given date. Some styles, such as ISO 8601, allow 24:00 to refer to the end of a day. Noon is 12:00:00.

text: While computers and digital clocks display "12:00 a.m." and "12:00 p.m.", those notations provide no clear and unambiguous way to distinguish between midnight and noon. Strictly speaking, it is actually incorrect to use "a.m." and "p.m." when referring to noon or midnight (12:00). The abbreviation a.m. stands for ante meridiem or before noon and p.m. stands for post meridiem or after noon. Since noon is neither after noon nor before noon, and midnight can equally be twelve hours before and after noon, neither abbreviation is correct (although the length of the error is determined by the smallest unit of time — 12:00:01 p.m. would be the correct notation for "1 second after noon").

text: The most common ways to represent these times are to:

text:
a) use a 24-hour clock (00:00 and 12:00, 24:00)
b) use "noon" or "midnight", although unless the person is referring to a general time and not a specific day, "midnight" is still ambiguous
c) specify the time between two successive days or dates (Midnight Saturday/Sunday or Midnight December 14/15)
d) use "12:01 a.m." or "11:59 p.m.", as is used where the ambiguity can have serious consequences, such as in contracts and insurance policies[1]

text: The thirtieth edition of the U.S. Government Style Manual (2008) sections 9.54 and 12.9b recommends the use of "12 a.m." for midnight and "12 p.m." for noon.[2][3][nb 1] Some religious calendars continue to begin the day at another time — for example, at sunset in the Hebrew calendar and the Islamic calendar.


document_title: List of Philadelphia Flyers seasons

question_text: when was the last time the flyers were in the playoffs

text: List of Philadelphia Flyers seasons

text: Table key[edit]

text:
Key of colors and symbols

Color/symbol
Explanation

Stanley Cup champions

Conference champions

Division champions

Led league in points

text:
Key of terms and abbreviations

Term or abbreviation
Definition

Finish
Final position in division standings

GA
Goals against (goals scored by the Flyers' opponents)

GF
Goals for (goals scored by the Flyers)

GP
Number of games played

L
Number of losses

OT
Number of losses in overtime (since the 1999–2000 season)

Pts
Number of points

ROW
Regulation + OT Wins (since the 2010–11 season)

T
Number of ties

W
Number of wins

—
Does not apply

text: Year by year[edit]

text:
Year by year listing of all seasons played by the Philadelphia Flyers

Season
Conference
Division
Regular season
Postseason

Finish
GP
W
L
T
OT
Pts
ROW
GF
GA
GP
W
L
GF
GA
Result

1967–68
—
West
1st
74
31
32
11
—
73
—
173
179
7
3
4
17
17
Lost Quarterfinals to St. Louis Blues, 3–4[3]

1968–69
—
West
3rd
76
20
35
21
—
61
—
174
225
4
0
4
3
17
Lost Quarterfinals to St. Louis Blues, 0–4[4]

1969–70
—
West
5th
76
17
35
24
—
58
—
197
225
—
—
—
—
—
Did not qualify

1970–71
—
West
3rd
78
28
33
17
—
73
—
207
225
4
0
4
8
20
Lost Quarterfinals to Chicago Black Hawks, 0–4[5]

1971–72
—
West
5th
78
26
38
14
—
66
—
200
236
—
—
—
—
—
Did not qualify

1972–73
—
West
2nd
78
37
30
11
—
85
—
296
256
11
5
6
27
31
Won Quarterfinals vs. Minnesota North Stars, 4–2
Lost Semifinals to Montreal Canadiens, 1–4[6]

1973–74
—
West
1st
78
50
16
12
—
112
—
273
164
17
12
5
54
36
Won Quarterfinals vs. Atlanta Flames, 4–0
Won Semifinals vs. New York Rangers, 4–3
Won Stanley Cup Finals vs. Boston Bruins, 4–2[7]

1974–75
Campbell[a]
Patrick
1st
80
51
18
11
—
113
—
293
181
17
12
5
53
34
Won Quarterfinals vs. Toronto Maple Leafs, 4–0
Won Semifinals vs. New York Islanders, 4–3
Won Stanley Cup Finals vs. Buffalo Sabres, 4–2[9]

1975–76
Campbell
Patrick
1st
80
51
13
16
—
118
—
348
209
16
8
8
56
52
Won Quarterfinals vs. Toronto Maple Leafs, 4–3
Won Semifinals vs. Boston Bruins, 4–1
Lost Stanley Cup Finals to Montreal Canadiens, 0–4[10]

1976–77
Campbell
Patrick
1st
80
48
16
16
—
112
—
323
213
10
4
6
27
32
Won Quarterfinals vs. Toronto Maple Leafs, 4–2
Lost Semifinals to Boston Bruins, 0–4[11]

1977–78
Campbell
Patrick
2nd
80
45
20
15
—
105
—
296
200
12
7
5
37
35
Won Preliminary Round vs. Colorado Rockies, 2–0
Won Quarterfinals vs. Buffalo Sabres, 4–1
Lost Semifinals to Boston Bruins, 1–4[12]

1978–79
Campbell
Patrick
2nd
80
40
25
15
—
95
—
281
248
8
3
5
23
37
Won Preliminary Round vs. Vancouver Canucks, 2–1
Lost Quarterfinals to New York Rangers, 1–4[13]

1979–80
Campbell
Patrick
1st
80
48
12
20
—
116
—
327
254
19
13
6
78
53
Won Preliminary Round vs. Edmonton Oilers, 3–0
Won Quarterfinals vs. New York Rangers, 4–1
Won Semifinals vs. Minnesota North Stars, 4–1
Lost Stanley Cup Finals to New York Islanders, 2–4[14]

1980–81
Campbell
Patrick
2nd
80
41
24
15
—
97
—
313
249
12
6
6
48
39
Won Preliminary Round vs. Quebec Nordiques, 3–2
Lost Quarterfinals to Calgary Flames, 3–4[15]

1981–82
Wales[b]
Patrick
3rd
80
38
31
11
—
87
—
325
313
4
1
3
15
19
Lost Division Semifinals to New York Rangers, 1–3[17]

1982–83
Wales
Patrick
1st
80
49
23
8
—
106
—
326
240
3
0
3
9
18
Lost Division Semifinals to New York Rangers, 0–3[18]

1983–84
Wales
Patrick
3rd
80
44
26
10
—
98
—
350
290
3
0
3
5
15
Lost Division Semifinals to Washington Capitals, 0–3[19]

1984–85
Wales
Patrick
1st
80
53
20
7
—
113
—
348
241
19
12
7
60
54
Won Division Semifinals vs. New York Rangers, 3–0
Won Division Finals vs. New York Islanders, 4–1
Won Conference Finals vs. Quebec Nordiques, 4–2
Lost Stanley Cup Finals to Edmonton Oilers, 1–4[20]

1985–86
Wales
Patrick
1st
80
53
23
4
—
110
—
335
241
5
2
3
15
18
Lost Division Semifinals to New York Rangers, 2–3[21]

1986–87
Wales
Patrick
1st
80
46
26
8
—
100
—
310
245
26
15
11
85
73
Won Division Semifinals vs. New York Rangers, 4–2
Won Division Finals vs. New York Islanders, 4–3
Won Conference Finals vs. Montreal Canadiens, 4–2
Lost Stanley Cup Finals to Edmonton Oilers, 3–4[22]

1987–88
Wales
Patrick
3rd
80
38
33
9
—
85
—
292
292
7
3
4
25
31
Lost Division Semifinals to Washington Capitals, 3–4[23]

1988–89
Wales
Patrick
4th
80
36
36
8
—
80
—
307
285
19
10
9
64
60
Won Division Semifinals vs. Washington Capitals, 4–2
Won Division Finals vs. Pittsburgh Penguins, 4–3
Lost Conference Finals to Montreal Canadiens, 2–4[24]

1989–90
Wales
Patrick
6th
80
30
39
11
—
71
—
290
297
—
—
—
—
—
Did not qualify

1990–91
Wales
Patrick
5th
80
33
37
10
—
76
—
252
267
—
—
—
—
—
Did not qualify

1991–92
Wales
Patrick
6th
80
32
37
11
—
75
—
252
273
—
—
—
—
—
Did not qualify

1992–93
Wales
Patrick
5th
84
36
37
11
—
83
—
319
319
—
—
—
—
—
Did not qualify

1993–94
Eastern[c]
Atlantic
6th
84
35
39
10
—
80
—
294
314
—
—
—
—
—
Did not qualify

1994–95
Eastern
Atlantic
1st
48[d]
28
16
4
—
60
—
150
132
15
10
5
50
43
Won Conference Quarterfinals vs. Buffalo Sabres, 4–1
Won Conference Semifinals vs. New York Rangers, 4–0
Lost Conference Finals to New Jersey Devils, 2–4[27]

1995–96
Eastern
Atlantic
1st
82
45
24
13
—
103
—
282
208
12
6
6
37
28
Won Conference Quarterfinals vs. Tampa Bay Lightning, 4–2
Lost Conference Semifinals to Florida Panthers, 2–4[28]

1996–97
Eastern
Atlantic
2nd
82
45
24
13
—
103
—
274
217
19
12
7
67
49
Won Conference Quarterfinals vs. Pittsburgh Penguins, 4–1
Won Conference Semifinals vs. Buffalo Sabres, 4–1
Won Conference Finals vs. New York Rangers, 4–1
Lost Stanley Cup Finals to Detroit Red Wings, 0–4[29]

1997–98
Eastern
Atlantic
2nd
82
42
29
11
—
95
—
242
193
5
1
4
9
18
Lost Conference Quarterfinals to Buffalo Sabres, 1–4[30]

1998–99
Eastern
Atlantic
2nd
82
37
26
19
—
93
—
231
196
6
2
4
11
9
Lost Conference Quarterfinals to Toronto Maple Leafs, 2–4[31]

1999–2000
Eastern
Atlantic
1st
82
45
22
12
3[e]
105
—
237
179
18
11
7
44
40
Won Conference Quarterfinals vs. Buffalo Sabres, 4–1
Won Conference Semifinals vs. Pittsburgh Penguins, 4–2
Lost Conference Finals to New Jersey Devils, 3–4[33]

2000–01
Eastern
Atlantic
2nd
82
43
25
11
3
100
—
240
207
6
2
4
13
21
Lost Conference Quarterfinals to Buffalo Sabres, 2–4[34]

2001–02
Eastern
Atlantic
1st
82
42
27
10
3
97
—
234
192
5
1
4
2
11
Lost Conference Quarterfinals to Ottawa Senators, 1–4[35]

2002–03
Eastern
Atlantic
2nd
82
45
20
13
4
107
—
211
166
13
6
7
34
33
Won Conference Quarterfinals vs. Toronto Maple Leafs, 4–3
Lost Conference Semifinals to Ottawa Senators, 2–4[36]

2003–04
Eastern
Atlantic
1st
82
40
21
15
6
101
—
229
186
18
11
7
50
43
Won Conference Quarterfinals vs. New Jersey Devils, 4–1
Won Conference Semifinals vs. Toronto Maple Leafs, 4–2
Lost Conference Finals to Tampa Bay Lightning, 3–4[37]

2004–05[f]
Eastern
Atlantic
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
No playoffs due to lockout

2005–06
Eastern
Atlantic
2nd
82
45
26
—[g]
11
101
—
267
259
6
2
4
14
27
Lost Conference Quarterfinals to Buffalo Sabres, 2–4[40]

2006–07
Eastern
Atlantic
5th
82
22
48
—
12
56
—
214
303
—
—
—
—
—
Did not qualify

2007–08
Eastern
Atlantic
4th
82
42
29
—
11
95
—
248
233
17
9
8
52
52
Won Conference Quarterfinals vs. Washington Capitals, 4–3
Won Conference Semifinals vs. Montreal Canadiens, 4–1
Lost Conference Finals to Pittsburgh Penguins, 1–4[41]

2008–09
Eastern
Atlantic
3rd
82
44
27
—
11
99
—
264
238
6
2
4
16
16
Lost Conference Quarterfinals to Pittsburgh Penguins, 2–4[42]

2009–10
Eastern
Atlantic
3rd
82
41
35
—
6
88
—
235
225
23
14
9
76
61
Won Conference Quarterfinals vs. New Jersey Devils, 4–1
Won Conference Semifinals vs. Boston Bruins, 4–3
Won Conference Finals vs. Montreal Canadiens, 4–1
Lost Stanley Cup Finals to Chicago Blackhawks, 2–4[43]

2010–11
Eastern
Atlantic
1st
82
47
23
—
12
106
44
259
223
11
4
7
29
38
Won Conference Quarterfinals vs. Buffalo Sabres, 4–3
Lost Conference Semifinals to Boston Bruins, 0–4[44]

2011–12
Eastern
Atlantic
3rd
82
47
26
—
9
103
43
264
232
11
5
6
41
44
Won Conference Quarterfinals vs. Pittsburgh Penguins, 4–2
Lost Conference Semifinals to New Jersey Devils, 1–4[45]

2012–13
Eastern
Atlantic
4th
48[h]
23
22
—
3
49
22
133
141
—
—
—
—
—
Did not qualify

2013–14
Eastern
Metropolitan[i]
3rd
82
42
30
—
10
94
39
236
235
7
3
4
16
19
Lost First Round to New York Rangers, 3–4[48]

2014–15
Eastern
Metropolitan
6th
82
33
31
—
18
84
30
215
234
—
—
—
—
—
Did not qualify

2015–16
Eastern
Metropolitan
5th
82
41
27
—
14
96
38
214
218
6
2
4
6
14
Lost First Round to Washington Capitals, 2–4[49]

2016–17
Eastern
Metropolitan
6th
82
39
33
—
10
88
32
219
236
—
—
—
—
—
Did not qualify

Season
Conference
Division
Regular season
Postseason

Finish
GP
W
L
T
OT
Pts
ROW
GF
GA
GP
W
L
GF
GA
Result

Totals
3,882
1,934
1,345
457
146
4,471
248
12,794
11,331
427
219
208
1,276
1,257
43–36 series record


document_title: Tongue map

question_text: where do we taste things on your tongue

question_tokens: where do we taste things on your tongue

text: Tongue map

text: The tongue map or taste map is a common misconception that different sections of the tongue are exclusively responsible for different basic tastes. It is illustrated with a schematic map of the tongue, with certain parts of the tongue labeled for each taste. Although widely taught in schools, this was scientifically disproven by later research; all taste sensations come from all regions of the tongue, although different parts are more sensitive to certain tastes.[1][2]

text: History[edit]

text: The theory behind this map originated from a paper written by Harvard psychologist D.P Hanig, which was a translation of a German paper, Zur Psychophysik des Geschmackssinnes, which was written in 1901.[3] The unclear representation of data in the former paper suggested that each part of the tongue tastes exactly one basic taste.[4][5]

text: The paper showed minute differences in threshold detection levels across the tongue,[6] but these differences were later taken out of context and the minute difference in threshold sensitivity was misconstrued in textbooks as a difference in sensation.[7]

text: While some parts of the tongue may be able to detect a taste before the others do, all parts are equally capable of conveying the qualia of all tastes. Threshold sensitivity may differ across the tongue, but intensity of sensation doesn't.[7]

text: The same paper included a taste bud distribution diagram that showed a "taste belt".[8]

text: In 1974, Virginia Collings investigated the topic again, and confirmed that all the tastes exist on all parts of the tongue.[9]

text: Taste belt[edit]

text: The misinterpreted 1901 diagram in the article that sparked this myth shows human taste buds distributed in a "taste belt" along the outside of the tongue.

text: Prior to this, A. Hoffmann had concluded, in 1875, that the dorsal center of the human tongue has practically no fungiform papillae and taste buds,[10] and it was this finding that the diagram describes.