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In engineering , a mechanism is a device that transforms input forces and movement into a desired set of output forces and movement. Mechanisms generally consist of moving components which may include Gears and gear trains ; Belts and chain drives ; cams and followers ; Linkages ; Friction devices, such as brakes or clutches ; Structural components such as a frame, fasteners, bearings, springs, or lubricants; Various machine elements , such as splines, pins, or keys.
German scientist Franz Reuleaux defines machine as "a combination of resistant bodies so arranged that by their means the mechanical forces of nature can be compelled to do work accompanied by certain determinate motion". In this context, his use of machine is generally interpreted to mean mechanism .
The combination of force and movement defines power , and a mechanism manages power to achieve a desired set of forces and movement.
A mechanism is usually a piece of a larger process, known as a mechanical system or machine . Sometimes an entire machine may be referred to as a mechanism; examples are the steering mechanism in a car , or the winding mechanism of a wristwatch .
However, typically, a set of multiple mechanisms is called a machine.
From the time of Archimedes to the Renaissance , mechanisms were viewed as constructed from simple machines , such as the lever , pulley , screw , wheel and axle , wedge , and inclined plane . Reuleaux focused on bodies, called links , and the connections between these bodies, called kinematic pairs , or joints.
To use geometry to study the movement of a mechanism, its links are modelled as rigid bodies . This means that distances between points in a link are assumed to not change as the mechanism moves—that is, the link does not flex. Thus, the relative movement between points in two connected links is considered to result from the kinematic pair that joins them.
Kinematic pairs, or joints, are considered to provide ideal constraints between two links, such as the constraint of a single point for pure rotation, or the constraint of a line for pure sliding, as well as pure rolling without slipping and point contact with slipping. A mechanism is modelled as an assembly of rigid links and kinematic pairs.
Reuleaux called the ideal connections between links kinematic pairs . He distinguished between higher pairs , with line contact between the two links, and lower pairs , with area contact between the links. J. Phillips [ clarification needed ] shows that there are many ways to construct pairs that do not fit this simple model.
Lower pair: A lower pair is an ideal joint that has surface contact between the pair of elements, as in the following cases:
Higher pairs: Generally, a higher pair is a constraint that requires a line or point contact between the elemental surfaces. For example, the contact between a cam and its follower is a higher pair called a cam joint . Similarly, the contact between the involute curves that form the meshing teeth of two gears are cam joints.
A kinematic diagram reduces machine components to a skeleton diagram that emphasises the joints and reduces the links to simple geometric elements. This diagram can also be formulated as a graph by representing the links of the mechanism as edges and the joints as vertices of the graph. This version of the kinematic diagram has proven effective in enumerating kinematic structures in the process of machine design. [ 1 ]
An important consideration in this design process is the degree of freedom of the system of links and joints, which is determined using the Chebychev–Grübler–Kutzbach criterion .
While all mechanisms in a mechanical system are three-dimensional, they can be analysed using plane geometry if the movement of the individual components is constrained so that all point trajectories are parallel or in a series connection to a plane. In this case the system is called a planar mechanism . The kinematic analysis of planar mechanisms uses the subset of Special Euclidean group SE , consisting of planar rotations and translations, denoted by SE.
The group SE is three-dimensional, which means that every position of a body in the plane is defined by three parameters. The parameters are often the x and y coordinates of the origin of a coordinate frame in M , [ clarification needed ] measured from the origin of a coordinate frame in F , and the angle measured from the x -axis in F to the x -axis in M . [ clarification needed ] This is often described saying a body in the plane has three degrees of freedom .
The pure rotation of a hinge and the linear translation of a slider can be identified with subgroups of SE, and define the two joints as one degree-of-freedom joints of planar mechanisms. [ incomprehensible ] The cam joint formed by two surfaces in sliding and rotating contact is a two degree-of-freedom joint.
It is possible to construct a mechanism such that the point trajectories in all components lie in concentric spherical shells around a fixed point. An example is the gimbaled gyroscope . These devices are called spherical mechanisms. [ 2 ] Spherical mechanisms are constructed by connecting links with hinged joints such that the axes of each hinge pass through the same point. This point becomes centre of the concentric spherical shells. The movement of these mechanisms is characterised by the group SO(3) [ clarification needed ] of rotations in three-dimensional space. Other examples of spherical mechanisms are the automotive differential and the robotic wrist.
The rotation group SO(3) is three-dimensional. An example of the three parameters that specify a spatial rotation are the roll, pitch and yaw angles used to define the orientation of an aircraft.
A mechanism in which a body moves through a general spatial movement is called a spatial mechanism . An example is the RSSR linkage, which can be viewed as a four-bar linkage in which the hinged joints of the coupler link are replaced by rod ends , also called spherical joints or ball joints . The rod ends let the input and output cranks of the RSSR linkage be misaligned to the point that they lie in different planes, which causes the coupler link to move in a general spatial movement. Robot arms , Stewart platforms , and humanoid robotic systems are also examples of spatial mechanisms.
Bennett's linkage is an example of a spatial overconstrained mechanism , which is constructed from four hinged joints.
The group SE(3) [ clarification needed ] is six-dimensional, which means the position of a body in space is defined by six parameters. Three of the parameters define the origin of the moving reference frame relative to the fixed frame. Three other parameters define the orientation of the moving frame relative to the fixed frame.
A linkage is a collection of links connected by joints. Generally, the links are the structural elements and the joints allow movement. Perhaps the single most useful example is the planar four-bar linkage . There are, however, many more special linkages:
A compliant mechanism is a series of rigid bodies connected by compliant elements. These mechanisms have many advantages, including reduced part-count, reduced "slop" between joints (no parasitic motion because of gaps between parts [ 3 ] ), energy storage, low maintenance (they don't require lubrication and there is low mechanical wear), and ease of manufacture. [ 4 ]
Flexure bearings (also known as flexure joints ) are a subset of compliant mechanisms that produce a geometrically well-defined motion (rotation) on application of a force.
A cam and follower mechanism is formed by the direct contact of two specially shaped links. The driving link is called the cam and the link that is driven through the direct contact of their surfaces is called the follower. The shape of the contacting surfaces of the cam and follower determines the movement of the mechanism. In general a cam and follower mechanism's energy is transferred from cam to follower. The camshaft is rotated and, according to the cam profile, the follower moves up and down. Nowadays, slightly different types of eccentric cam followers are also available, in which energy is transferred from the follower to the cam. The main benefit of this type of cam and follower mechanism is that the follower moves slightly and helps to rotate the cam six times more circumference length with 70% of the force.
The transmission of rotation between contacting toothed wheels can be traced back to the Antikythera mechanism of Greece and the south-pointing chariot of China. Illustrations by the Renaissance scientist Georgius Agricola show gear trains with cylindrical teeth. The implementation of the involute tooth yielded a standard gear design that provides a constant speed ratio. Some important features of gears and gear trains are:
The design of mechanisms to achieve a particular movement and force transmission is known as the kinematic synthesis of mechanisms . [ 5 ] This is a set of geometric techniques which yield the dimensions of linkages, cam and follower mechanisms, and gears and gear trains to perform a required mechanical movement and power transmission. [ 6 ] | https://en.wikipedia.org/wiki/Mechanism_(engineering) |
In pharmacology , the term mechanism of action ( MOA ) refers to the specific biochemical interaction through which a drug substance produces its pharmacological effect . [ 2 ] A mechanism of action usually includes mention of the specific molecular targets to which the drug binds, such as an enzyme or receptor . [ 3 ] Receptor sites have specific affinities for drugs based on the chemical structure of the drug, as well as the specific action that occurs there.
Drugs that do not bind to receptors produce their corresponding therapeutic effect by simply interacting with chemical or physical properties in the body. Common examples of drugs that work in this way are antacids and laxatives . [ 2 ]
In contrast, a mode of action (MoA) describes functional or anatomical changes, at the cellular level, resulting from the exposure of a living organism to a substance.
Elucidating the mechanism of action of novel drugs and medications is important for several reasons:
Bioactive compounds induce phenotypic changes in target cells, changes that are observable by microscopy and that can give insight into the mechanism of action of the compound. [ 13 ]
With antibacterial agents , the conversion of target cells to spheroplasts can be an indication that peptidoglycan synthesis is being inhibited, and filamentation of target cells can be an indication that PBP 3, FtsZ , or DNA synthesis is being inhibited. Other antibacterial agent-induced changes include ovoid cell formation, pseudomulticellular forms, localized swelling, bulge formation, blebbing, and peptidoglycan thickening. [ 4 ] In the case of anticancer agents , bleb formation can be an indication that the compound is disrupting the plasma membrane . [ 14 ]
A current limitation of this approach is the time required to manually generate and interpret data, but advances in automated microscopy and image analysis software may help resolve this. [ 4 ] [ 13 ]
Direct biochemical methods include methods in which a protein or a small molecule, such as a drug candidate, is labeled and is traced throughout the body. [ 15 ] This proves to be the most direct approach to find target protein that will bind to small targets of interest, such as a basic representation of a drug outline, in order to identify the pharmacophore of the drug. Due to the physical interactions between the labeled molecule and a protein, biochemical methods can be used to determine the toxicity, efficacy, and mechanism of action of the drug. [ citation needed ]
Typically, computation inference methods are primarily used to predict protein targets for small molecule drugs based on computer based pattern recognition. [ 15 ] However, this method could also be used for finding new targets for existing or newly developed drugs. By identifying the pharmacophore of the drug molecule, the profiling method of pattern recognition can be carried out where a new target is identified. [ 15 ] This provides an insight at a possible mechanism of action since it is known what certain functional components of the drug are responsible for when interacting with a certain area on a protein, thus leading to a therapeutic effect. [ citation needed ]
Omics based methods use omics technologies, such as chemoproteomics , reverse genetics and genomics , transcriptomics , and proteomics , to identify the potential targets of the compound of interest. [ 16 ] Reverse genetics and genomics approaches, for instance, uses genetic perturbation (e.g. CRISPR - Cas9 or siRNA ) in combination with the compound to identify genes whose knockdown or knockout abolishes the pharmacological effect of the compound. On the other hand, transcriptomics and proteomics profiles of the compound can be used to compare with profiles of compounds with known targets. Thanks to computation inference, it is then possible to make hypotheses about the mechanism of action of the compound, which can subsequently be tested. [ 16 ]
There are many drugs in which the mechanism of action is known. One example is aspirin. [ citation needed ]
The mechanism of action of aspirin involves irreversible inhibition of the enzyme cyclooxygenase ; [ 17 ] therefore suppressing the production of prostaglandins and thromboxanes , thus reducing pain and inflammation. This mechanism of action is specific to aspirin and is not constant for all nonsteroidal anti-inflammatory drugs (NSAIDs). Rather, aspirin is the only NSAID that irreversibly inhibits COX-1. [ 18 ]
Some drug mechanisms of action are still unknown. However, even though the mechanism of action of a certain drug is unknown, the drug still functions; it is just unknown or unclear how the drug interacts with receptors and produces its therapeutic effect.
In some literature articles, the terms "mechanism of action" and " mode of action " are used interchangeably, typically referring to the way in which the drug interacts and produces a medical effect. However, in actuality, a mode of action describes functional or anatomical changes, at the cellular level, resulting from the exposure of a living organism to a substance. [ 19 ] This differs from a mechanism of action since it is a more specific term that focuses on the interaction between the drug itself and an enzyme or receptor and its particular form of interaction, whether through inhibition , activation , agonism , or antagonism . Furthermore, the term "mechanism of action" is the main term that is primarily used in pharmacology, whereas "mode of action" will more often appear in the field of microbiology or certain aspects of biology. [ citation needed ] | https://en.wikipedia.org/wiki/Mechanism_of_action |
Sonoluminescence is a phenomenon that occurs when a small gas bubble is acoustically suspended and periodically driven in a liquid solution at ultrasonic frequencies, resulting in bubble collapse, cavitation , and light emission. The thermal energy that is released from the bubble collapse is so great that it can cause weak light emission. [ 1 ] The mechanism of the light emission remains uncertain, but some of the current theories, which are categorized under either thermal or electrical processes, are Bremsstrahlung radiation, argon rectification hypothesis, [ 2 ] and hot spot. Some researchers are beginning to favor thermal process explanations as temperature differences have consistently been observed with different methods of spectral analysis. [ 3 ] In order to understand the light emission mechanism, it is important to know what is happening in the bubble's interior and at the bubble's surface.
Prior to the early 1990s, the studies on different chemical and physical variables of sonoluminescence were all conducted using multi-bubble sonoluminescence (MBSL). [ 4 ] This was a problem since all of the theories and bubble dynamics were based on single bubble sonoluminescence (SBSL) and researchers believed that the bubble oscillations of neighboring bubbles could affect each other. [ 4 ] Single bubble sonoluminescence wasn't achieved until the early 1990s and allowed the study of the effects of various parameters on a single cavitating bubble. [ 4 ] After many of the early theories were disproved, the remaining plausible theories can be classified into two different processes: electrical and thermal. [ 1 ] [ 4 ]
SBSL emits more light than MBSL due to fewer interactions between neighboring bubbles. [ 4 ] Another advantage for SBSL is that a single bubble collapses without being affected by other surrounding bubbles, allowing more accurate studies on acoustic cavitation and sonoluminescence theories. [ 4 ] Some exotic theories have been made, for example from Schwinger in 1992 who hinted the dynamical Casimir effect as a potential photon-emission process. Several theories say that the location of light emission is in the liquid instead of inside the bubble. Other SBSL theories explain that the emission of photons due to the high temperatures in the bubble are analogical to the hot spot theories of MBSL. Regarding the thermal emission a large variety of different processes are prevalent. Because temperatures are increasing from several hundred to many thousand kelvin during collapse, the processes can be molecular recombination, collision-induced emission, molecular emission, excimers, atomic recombination, radiative attachments of ions, neutral and ion Bremsstrahlung , or emission from confined electrons in voids. Which of these theories applies depends on accurate measurements and calculations of the temperature inside the bubble. [ 1 ]
Unlike single-bubble sonoluminescence, multi-bubble sonoluminescence is the creation of many oscillating and collapsing bubbles. Typically in MBSL, the light emission from each individual bubble is weaker than in SBSL because the neighboring bubbles can interact and affect each other. [ 4 ] Because each neighboring bubble can interact with each other, it can make it more difficult to produce accurate studies and to characterize the properties of the collapsing bubble.
One of the greatest obstacles in sonoluminescence research has been trying to obtain measurements of the interior of the bubble. Most measurements, like temperature and pressure, are indirectly measured using models and bubble dynamics. [ 1 ]
Some of the developed theories about the mechanism of SBSL result in prognoses for the peak temperature from 6000 K to 20,000 K. What they all have in common is, a) the interior of the bubble heats up and becomes at least as hot as that measured for MBSL, b) water vapor is the main temperature-limiting factor and c) the averaged temperature over the bubble does not rise higher than 10,000 K. [ 1 ]
These equations were made using five major assumptions, [ 5 ] with four of them being common to all the equations:
The fifth assumption, which changes between each formulation, pertains to the thermodynamic behavior of the liquid surrounding the bubble. These assumptions severely limit the models when the pulsations are large and the wall velocities reach the speed of sound .
The Keller–Miksis formulation is an equation derived for the large, radial oscillations of a bubble trapped in a sound field. When the frequency of the sound field approaches the natural frequency of the bubble, it will result in large amplitude oscillations. The Keller–Miksis equation takes into account the viscosity, surface tension, incident sound wave, and acoustic radiation coming from the bubble, which was previously unaccounted for in Lauterborn's calculations. Lauterborn solved the equation that Plesset, et al. modified from Rayleigh's original analysis of large oscillating bubbles. [ 6 ] Keller and Miksis obtained the following formula: [ 5 ]
where R {\displaystyle R} is the radius of the bubble, the dots indicate first and second time derivatives, ρ l {\displaystyle \rho _{l}} is the density of the liquid, c {\displaystyle c} is the speed of sound through the liquid, p B ( R , t ) {\displaystyle p_{B}(R,t)} is the pressure on the liquid side of the bubble's interface, t {\displaystyle t} is time, and p A ( t + R / c ) {\displaystyle p_{A}(t+R/c)} is the time-delayed driving pressure.
Prosperetti found a way to accurately determine the internal pressure of the bubble using the following equation. [ 7 ]
where T {\displaystyle T} is the temperature, K {\displaystyle K} is the thermal conductivity of the gas, and r {\displaystyle r} is the radial distance.
This formulation allows the study of the motions and the effects of heat conduction, shear viscosity, compressibility, and surface tension on small cavitation bubbles in liquids that are set into motion by an acoustic pressure field. The effect of vapor pressure on the cavitation bubble can also be determined using the interfacial temperature. The formulation is specifically designed to describe the motion of a bubble that expands to a maximum radius and then violently collapses or contracts. [ 8 ] This set of equations was solved using an improved Euler method .
where R {\displaystyle R} is the radius of the bubble, the dots indicate first and second time derivatives, ρ l {\displaystyle \rho _{l}} is the density of the liquid, c {\displaystyle c} is the speed of sound through the liquid, d p B ( R , t ) {\displaystyle dp_{B}(R,t)} is the pressure on the liquid side of the bubble's interface, t {\displaystyle t} is time, and p A ( t ) {\displaystyle p_{A}(t)} is the driving pressure.
The theory of bubble dynamics was started in 1917 by Lord Rayleigh during his work with the Royal Navy to investigate cavitation damage on ship propellers. Over several decades his work was refined and developed by Milton Plesset , Andrea Prosperetti , and others. [ 1 ] The Rayleigh–Plesset equation [ 1 ] is:
where R {\displaystyle R} is the bubble radius, R ¨ {\displaystyle {\ddot {R}}} is the second order derivative of the bubble radius with respect to time, R ˙ {\displaystyle {\dot {R}}} is the first order derivative of the bubble radius with respect to time, ρ l {\displaystyle \rho _{l}} is the density of the liquid, p g {\displaystyle p_{g}} is the pressure in the gas (which is assumed to be uniform), P 0 {\displaystyle P_{0}} is the background static pressure, P ( t ) {\displaystyle P(t)} is the sinusoidal driving pressure, μ {\displaystyle \mu } is the viscosity of the liquid, and γ {\displaystyle \gamma } is the surface tension of the gas-liquid interface.
The surface of a collapsing bubble like those seen in both SBSL and MBSL serves as a boundary layer between the liquid and vapor phases of the solution.
MBSL has been observed in many different solutions under a variety of conditions. Unfortunately it is more difficult to study as the bubble cloud is uneven and can contain a wide range of pressures and temperatures. SBSL is easier to study due to the predictable nature of the bubble. This bubble is sustained in a standing acoustic wave of moderate pressure, approximately 1.5 atm. [ 9 ] Since cavitation does not normally occur at these pressures the bubble may be seeded through several techniques:
The standing acoustic wave, which contains pressure antinodes at the center of the containment vessel, causes the bubbles to quickly coalesce into a single radially oscillating bubble.
Once a single bubble is stabilized in the pressure antinode of the standing wave, it can be made to emit pulses of light by driving the bubble into highly nonlinear oscillations. This is done by the increasing pressure of the acoustic wave to disrupt the steady, linear growth of the bubble which cause the bubble to collapse in a runaway reaction that only reverts due to the high pressures inside the bubble at its minimum radius.
The collapsed bubble expands due to high internal pressure and experiences a diminishing effect until the high pressure antinode returns to the center of the vessel. The bubble continues to occupy more or less the same space due to the acoustic radiation force, the Bjerknes force , and the buoyancy force of the bubble.
The effect that different chemicals present in solution have to the velocity of the collapsing bubble has recently been studied. Nonvolatile liquids such as sulfuric and phosphoric acid have been shown to produce flashes of light several nanoseconds in duration with a much slower bubble wall velocity, [ 10 ] and producing several thousand-fold greater light emission. This effect is probably masked in SBSL in aqueous solutions by the absorption of light by water molecules and contaminants.
It can be inferred from these results that the difference in surface tension between these different compounds is the source of different spectra emitted and the time scales in which emission occur.
The inertia of a collapsing bubble generates high pressures and temperatures capable of ionizing a small fraction of the noble gas within the volume of the bubble. This small fraction of ionized gas is transparent and allows for volume emission to be detected. Free electrons from the ionized noble gas begin to interact with other neutral atoms causing thermal bremsstrahlung radiation. Surface emission emits a more intense flash of light with a longer duration and is dependent on wavelength. Experimental data suggest that only volume emission occurs in the case of sonoluminescence. [ 1 ] As the sound wave reaches a low energy trough, the bubble expands and electrons are able to recombine with free ions and halt light emission. Light pulse time is dependent on the ionization energy of the noble gas with argon having a light pulse of 160 picoseconds.
In 1937, the explanations for the light emission have favored electrical discharges. The first ideas have been about the charge separation in cavitation bubbles, which have been seen as spherical capacitors with charges at the center and the wall.
At the collapse, the capacitance decreases and voltage increases until electric breakdown occurs. A further suggestion was a charge separation by enhancing charge fluctuations on the bubble wall, however, a breakdown should take place during the expansion phase of the bubble dynamics.
These discharge theories have to assume that the emitting bubble undergoes an asymmetric collapse, because a symmetric charge distribution cannot radiate light. [ 1 ]
Because the bubble collapse occurs within microseconds, [ 5 ] the hot spot theory states that the thermal energy results from an adiabatic bubble collapse. In 1950 it was assumed that the bubble internal temperatures were as high as 10,000 K at the collapse of a spherical symmetric bubble. [ 1 ] In the 1990s, sonoluminescence spectra were used by Suslick to measure effective emission temperatures in bubble clouds (multibubble sonoluminescence) of 5000 K, [ 12 ] [ 13 ] and more recently temperatures as high as 20,000 K in single bubble cavitation. [ 10 ] [ 14 ] [ 15 ]
The limit for the ambient size of the bubble is set by the appearance of instabilities in the shape of the oscillating bubble.
The shape stability thresholds depend on changes in the radial dynamics, caused by different liquid viscosities or driving frequencies. If the frequency is decreased, the parametric instability is suppressed as the stabilizing influence of viscosity can appear longer to suppress perturbations. However, the collapses of low-frequency-driven bubbles favor an earlier onset of the Rayleigh-Taylor instability. Larger bubbles can be stabilized to show sonoluminescence when not too high forcing pressures are applied. At low-frequency the water vapor becomes more important. The bubbles can be stabilized by cooling the fluid, whereas more light is emitted. [ 1 ] | https://en.wikipedia.org/wiki/Mechanism_of_sonoluminescence |
Mindfulness has been defined in modern psychological terms as "paying attention to relevant aspects of experience in a nonjudgmental manner", [ 1 ] and maintaining attention on present moment experience with an attitude of openness and acceptance. [ 2 ] Meditation is a platform used to achieve mindfulness. Both practices, mindfulness and meditation, have been "directly inspired from the Buddhist tradition" [ 3 ] and have been widely promoted by Jon Kabat-Zinn . Mindfulness meditation has been shown to have a positive impact on several psychiatric problems such as depression and therefore has formed the basis of mindfulness programs [ 4 ] such as mindfulness-based cognitive therapy , mindfulness-based stress reduction and mindfulness-based pain management . The applications of mindfulness meditation are well established, however the mechanisms that underlie this practice are yet to be fully understood. Many tests and studies on soldiers with PTSD have shown tremendous positive results in decreasing stress levels and being able to cope with problems of the past, paving the way for more tests and studies to normalize and accept mindful based meditation and research, not only for soldiers with PTSD, but numerous mental inabilities or disabilities. [ 5 ]
Four components of mindfulness meditation have been proposed to describe much of the mechanism of action by which mindfulness meditation may work: attention regulation, body awareness, emotion regulation, and change in perspective on the self. [ 4 ] All of the components described above are connected to each other. For example, when a person is triggered by an external stimulus, the executive attention system attempts to maintain a mindful state . There is also a heightened body awareness such as a rapid heartbeat which triggers an emotional response. The response is then regulated so that it does not become habitual, but constantly changes from moment to moment experience. This eventually leads to a change in the perspective of the self.
Attention regulation is the task of focusing attention on an object, acknowledging any distractions, and then returning your focus back to the object. Some evidence for mechanisms responsible for attention regulation during mindfulness meditation are shown below.
The ACC detects conflicting information coming from distractions. When a person is presented with a conflicting stimulus, the brain initially processes the stimulus incorrectly. This is known as error-related negativity (ERN). Before the ERN reaches a threshold , the correct conflict is detected by the frontocentral N2 . After the correction, the rostral ACC is activated and allows for executive attention to the correct stimulus. [ 11 ] Therefore, mindfulness meditation could potentially be a method for treating attention related disorders such as ADHD and bipolar disorder .
Body awareness refers to focusing on an object/task within the body such as breathing. From a qualitative interview with ten mindfulness meditators, some of the following responses were observed: "When I'm walking, I deliberately notice the sensations of my body moving" and "I notice how foods and drinks affect my thoughts, bodily sensations, and emotions”. [ 12 ] The two possible mechanisms by which a mindfulness meditator can experience body awareness are discussed below.
The insula is responsible for awareness to stimuli and the thickness of its gray matter correlates to the accuracy and detection of the stimuli by the nervous system. [ 16 ] [ 17 ] Qualitative evidence suggests that mindfulness meditation impacts body awareness, however this component is not well characterized. [ 4 ]
Emotions can be regulated cognitively or behaviorally. Cognitive regulation (in terms of mindfulness meditation) means having control over giving attention to a particular stimuli or by changing the response to that stimuli. The cognitive change is achieved through reappraisal (interpreting the stimulus in a more positive manner) and extinction (reversing the response to the stimulus). Behavioral regulation refers to inhibiting the expression of certain behaviors in response to a stimulus. Research suggests two main mechanisms for how mindfulness meditation influences the emotional response to a stimulus.
Lateral prefrontal cortex (lPFC) is important for selective attention while ventral prefrontal cortex (vPFC) is involved in inhibiting a response. As noted before, the anterior cingulate cortex (ACC) has been noted for maintaining attention to a stimulus. The amygdala is responsible for generating emotions. Mindfulness meditation is believed to be able to regulate negative thoughts and decrease emotional reactivity through these regions of the brain. Emotion regulation deficits have been noted in disorders such as borderline personality disorder [ 22 ] and depression . [ 23 ] These deficits have been associated with reduced prefrontal activation and increased amygdala activity, which mindfulness meditation might be able to attenuate.
Pain is known to activate the following regions of the brain: the anterior cingulate cortex , anterior/posterior insula , primary/secondary somatosensory cortices, and the thalamus . [ 24 ] Mindfulness meditation may provide several methods by which a person can consciously regulate pain. [ 24 ]
Brown and Jones found that meditators showed no difference in pain sensitivity but rather the anticipation in pain. However, Grant's research showed that meditators experienced lower sensitivity to pain. These conflicting studies illustrate that the exact mechanism may vary with the expertise level or meditation technique. [ 24 ] | https://en.wikipedia.org/wiki/Mechanisms_of_mindfulness_meditation |
Mechanobiology is an emerging field of science at the interface of biology, engineering, chemistry and physics. It focuses on how physical forces and changes in the mechanical properties of cells and tissues contribute to development, cell differentiation, physiology , and disease. Mechanical forces are experienced and may be interpreted to give biological responses in cells. The movement of joints, compressive loads on the cartilage and bone during exercise, and shear pressure on the blood vessel during blood circulation are all examples of mechanical forces in human tissues. [ 1 ] A major challenge in the field is understanding mechanotransduction —the molecular mechanisms by which cells sense and respond to mechanical signals. While medicine has typically looked for the genetic and biochemical basis of disease, advances in mechanobiology suggest that changes in cell mechanics, extracellular matrix structure, or mechanotransduction may contribute to the development of many diseases, including atherosclerosis , fibrosis , asthma , osteoporosis , heart failure , and cancer . There is also a strong mechanical basis for many generalized medical disabilities, such as lower back pain, foot and postural injury, deformity, and irritable bowel syndrome . [ 2 ]
Skin fibroblasts are vital in development and wound repair and they are affected by mechanical cues like tension, compression and shear pressure. Fibroblasts synthesize structural proteins, some of which are mechanosensitive and form integral part of the extracellular Matrix (ECM) e.g. collagen types I, III, IV, V VI, elastin , lamin etc. In addition to the structural proteins, fibroblasts make Tumor-Necrosis-Factor - alpha (TNF-α), Transforming-Growth-Factor-beta (TGF-β) and matrix metalloproteases that plays in tissue in tissue maintenance and remodeling. [ 3 ]
Articular cartilage is the connective tissue that protects bones of load-bearing joints like knee, shoulder by providing a lubricated surface. It deforms in response to compressive load, thereby reducing stress on bones. [ 4 ] This mechanical responsiveness of articular cartilage is due to its biphasic nature; it contains both the solid and fluid phases. The fluid phase is made up of water -which contributes 80% of the wet weight – and inorganic ions e.g. Sodium ion, Calcium ion and Potassium ion. The solid phase is made up of porous ECM. The proteoglycans and interstitial fluids interact to give compressive force to the cartilage through negative electrostatic repulsive forces. The ion concentration difference between the extracellular and intracellular ions composition of chondrocytes result in hydrostatic pressure. [ 5 ] During development, mechanical environment of joint determines surface and topology of the joint. [ 6 ] In adult, moderate mechanical loading is required to maintain cartilage; immobilization of joint leads to loss of proteoglycans and cartilage atrophy while excess mechanical loading results in degeneration of joint. [ 7 ]
The nucleus is also responsive to mechanical signals which are relayed from the extracellular matrix through the cytoskeleton by the help of Linker of Nucleoskeleton and Cytoskeleton LINC-associated proteins like KASH and SUN. [ 8 ] Examples of effect of mechanical responses in the nucleus involve:
The embryo is formed by self-assembly through which cells differentiate into tissues performing specialized functions. It was previously believed that only chemical signals give cues that control spatially oriented changes in cell growth, differentiation and fate switching that mediate morphogenetic controls. This is based on the ability of chemical signals to induce biochemical responses like tissue patterning in distant cells. However, it is now known that mechanical forces generated within cells and tissues provide regulatory signals. [ 10 ]
During the division of the fertilized oocyte , cells aggregate and the compactness between cells increases with the help of actomyosin-dependent cytoskeletal traction forces and their application to adhesive receptors in neighboring cells, thereby leading to formation of solid balls called Morula . [ 11 ] The spindle positioning within symmetrically and asymmetrically dividing cells in the early embryo is controlled by mechanical forces mediated by microtubules and actin microfilament system. [ 12 ] Local variation in physical forces and mechanical cues such as stiffness of the ECM also control the expression of genes that give rise to the embryonic developmental process of blastulation . The loss of stiffness-controlled transcription factor Cdx leads to the ectopic expression of inner cell mass markers in the trophectoderm, and the pluripotent transcription factor, Oct-4 may be negatively expressed, thereby inducing lineage switching. This cell fate switching is regulated by the mechanosensitive hippo pathway [ 13 ]
The effectiveness of many of the mechanical therapies already in clinical use shows how important physical forces can be in physiological control. Several examples illustrate this point. Pulmonary surfactant promotes lung development in premature infants; modifying the tidal volumes of mechanical ventilators reduces morbidity and death in patients with acute lung injury. Expandable stents physically prevent coronary artery constriction. Tissue expanders increase the skin area available for reconstructive surgery. [ 14 ] Surgical tension application devices are used for bone fracture healing, orthodontics, cosmetic breast expansion and closure of non-healing wounds. [ citation needed ]
Insights into the mechanical basis of tissue regulation may also lead to development of improved medical devices, biomaterials , and engineered tissues for tissue repair and reconstruction. [ 15 ]
Known contributors to cellular mechanotransduction are a growing list and include stretch-activated ion channels , caveolae , integrins , cadherins , growth factor receptors, myosin motors, cytoskeletal filaments, nuclei , extracellular matrix, and numerous other signaling molecules. Endogenous cell-generated traction forces also contribute significantly to these responses by modulating tensional prestress within cells, tissues, and organs that govern their mechanical stability, as well as mechanical signal transmission from the macroscale to the nanoscale. [ 16 ] [ 17 ] | https://en.wikipedia.org/wiki/Mechanobiology |
Mechanochromic luminescence (ML) references to intensity and/or color changes of (solid-state) luminescent materials induced by mechanical forces, such as rubbing, crushing, pressing, shearing, or smearing. Unlike " triboluminescence " which does not require additional excitation source other than force itself, ML is often manifested by external photoexcitation such as a UV lamp. [ 1 ] The most common cause of ML is related to changes of intermolecular interactions of dyes and pigments , which gives rise to various strong ( exciton splitting) and/or weak ( Forster ) excited state interactions. For example, a certain boron complex of sunscreen compound avobenzone exhibits reversible ML. A recent detailed study [ 2 ] suggests that ML from the boron complex consists of two critical coupled steps: 1) generation of low energy exciton trap via mechanical perturbation; and 2) exciton migration from regions where photoexcitation results in a higher excited state . Since solid-state energy transfer can be very efficient, only a small fraction of the low-energy exciton traps is required when mechanical force is applied. As a result, for crystalline ML materials, XRD measurement may not able to detect changes before and after mechanical stimuli while its photoluminescence can be quite different. | https://en.wikipedia.org/wiki/Mechanochromic_luminescence |
The change of colour which occurs when chemicals are put under stress in the solid state by mechanical grinding, crushing and milling; by friction and rubbing; or in the solid or solution state by high pressure or sonication is covered by the generic term mechanochromism . Specifically colour change under pressure is known as piezochromism and under grinding or attrition tribochromism .
1. Bamfield, Peter and Hutchings, Michael G, Chromic Phenomena: the technological applications of colour chemistry, Royal Society of Chemistry, Cambridge UK, pages 104–5, 2010. ISBN 978-1-84755-868-8 .
This article about materials science is a stub . You can help Wikipedia by expanding it .
This spectroscopy -related article is a stub . You can help Wikipedia by expanding it . | https://en.wikipedia.org/wiki/Mechanochromism |
Mechanoluminescence is light emission resulting from any mechanical action on a solid. It can be produced through ultrasound, or through other means. | https://en.wikipedia.org/wiki/Mechanoluminescence |
Mechanophilia (or mechaphilia [ 1 ] ) is a paraphilia involving a sexual attraction to machines such as bicycles, motorcycles, [ 2 ] cars, [ 3 ] [ 4 ] helicopters, [ 5 ] and airplanes. [ 6 ]
Mechanophilia is treated as a crime in some nations with perpetrators being placed on a sex-offenders' register after prosecution. [ 7 ] Motorcycles are often portrayed as sexualized fetish objects to those who desire them. [ 8 ]
In 2015 a man in Thailand was caught on CCTV masturbating himself on the front end of a Porsche . [ 9 ]
In 2008, an American named Edward Smith admitted to 'having sex' with 1000 cars, and the helicopter used in the television show Airwolf . [ 10 ]
Mechanophilia has been used to describe important works of the early modernists , including in the Eccentric Manifesto (1922), [ 11 ] written by Leonid Trauberg , Sergei Yutkevich , Grigori Kozintsev and others [ 12 ] [ 13 ] – members of the Factory of the Eccentric Actor , a modernist avant-garde movement that spanned Russian futurism and constructivism .
The term has entered into the realms of science fiction and popular fiction. [ 14 ]
Scientifically, in Biophilia – The Human Bond with Other Species by Edward O. Wilson , Wilson is quoted describing mechanophilia, the love of machines, as "a special case of biophilia ", [ 15 ] whereas psychologists such as Erich Fromm would see it as a form of necrophilia . [ 16 ]
Designers such as Francis Picabia and Filippo Tommaso Marinetti have been said to have exploited the sexual attraction of automobiles. [ 17 ]
Culturally, critics have described it as "all-pervading" within contemporary Western society and that it seems to overwhelm our society and all too often our better judgment. [ 18 ] Although not all such uses are sexual in intent, the terms are also used for specifically erotogenic fixation on machinery [ 19 ] and taken to its extreme in hardcore pornography as Fucking Machines . [ 20 ] This mainly involves women being sexually penetrated by machines for male consumption, [ 21 ] which are seen as being the limits of current sexual biopolitics. [ 22 ]
Arse Elektronika , an annual conference organized by the Austrian arts-and-philosophy collective monochrom , has propagated a DIY/feminist approach to sex machines. [ 23 ]
Authors have drawn a connection between mechanophilia and masculine militarisation, citing the works of animator Yasuo Ōtsuka and Studio Ghibli . [ 24 ]
The 1973 French film La Grande Bouffe includes a scene of a man and a car copulating, to fatal effect.
David Cronenberg's 1996 film Crash concerns a cult of people fascinated by car crashes.
The 2021 French film and Palme d'Or winner Titane depicts scenes of a mechanophilic woman having sex with cars. | https://en.wikipedia.org/wiki/Mechanophilia |
The Mechanostat is a term describing the way in which mechanical loading influences bone structure by changing the mass (amount of bone) and architecture (its arrangement) to provide a structure that resists habitual loads with an economical amount of material. As changes in the skeleton are accomplished by the processes of formation ( bone growth ) and resorption (bone loss), the mechanostat models the effect of influences on the skeleton by those processes, through their effector cells, osteocytes, osteoblasts, and osteoclasts. The term was invented by Harold Frost : an orthopaedic surgeon and researcher described extensively in articles referring to Frost and Webster Jee's Utah Paradigm of Skeletal Physiology [ 1 ] [ 2 ] [ 3 ] [ 4 ] [ 5 ] in the 1960s. The Mechanostat is often defined as a practical description of Wolff's law described by Julius Wolff (1836–1902), but this is not completely accurate. Wolff wrote his treatises on bone after images of bone sections were described by Culmann and von Meyer, who suggested that the arrangement of the struts (trabeculae) at the ends of the bones were aligned with the stresses experienced by the bone. It has since been established that the static methods used for those calculations of lines of stress were inappropriate for work on what were, in effect, curved beams, a finding described by Lance Lanyon, a leading researcher in the area as "a triumph of a good idea over mathematics." While Wolff pulled together the work of Culmann and von Meyer, it was the French scientist Roux, who first used the term "functional adaptation" to describe the way that the skeleton optimized itself for its function, though Wolff is credited by many for that.
According to the Mechanostat, bone growth and bone loss is stimulated by the local, mechanical, elastic deformation of bone. The reason for the elastic deformation of bone is the peak forces caused by muscles (e.g. measurable using mechanography ). The adaptation (feed-back control loop ) of bone according to the maximum forces is considered to be a lifelong process. Hence, bone adapts its mechanical properties according to the needed mechanical function: bone mass, bone geometry, and bone strength (see also Stress-strain index , SSI) adapt to everyday usage/needs. "Maximal force" in this context is a simplification of the real input to bone that initiates adaptive changes. While the magnitude of a force (the weight of a load for example) is an important determinant of its effect on the skeleton, it is not the only one. The rate of application of force is also critical. Slow application of force over several seconds is not experienced by bone cells as a stimulus, but they are sensitive to very rapid application of forces (such as impacts) even of lower magnitude. High frequency vibration of bone at very low magnitudes is thought to stimulate changes, but the research in the area is not completely unequivocal. It is clear that bones respond better to loading/exercise with gaps between individual events, so that two loads separated by ten seconds of rest are more potent stimuli than ten loads within the same ten seconds.
Due to this control loop, there is a linear relationship in the healthy body between muscle cross sectional area (as a surrogate for typical maximum forces the muscle is able to produce under physiological conditions) and the bone cross sectional area (as a surrogate for bone strength). [ 6 ] [ 7 ]
These relations are of immense importance, especially for conditions of bone loss like osteoporosis , since an adapted training utilizing the needed maximum forces on the bone can be used to stimulate bone growth and thereby prevent or help to minimize bone loss. An example for such an efficient training is vibration training or whole body vibration .
Frost defined four regions of elastic bone deformation which result in different consequences on the control loop:
According to this, a typical bone (e.g., the tibia ) has a security margin of about 5 to 7 between typical load (2000 to 3000 μStrain) and fracture load (about 15000μStrain).
The comments above are all one part of how the skeleton responds to loading, because the different bones of the skeleton have a range of habitual strain environments (encompassing magnitude, rate, frequency, rest periods, etc.), and they are not uniform. The numbers in the table are only theoretical and may reflect the response of the center of a long bone under specific circumstances. Other parts of the same bone and other bones in the same individual experience different loading and adapt to them despite different thresholds between disuse, maintenance and adaptive formation. Furthermore, bone structure is controlled by a complex series of different influences, such as calcium status, the effects of hormones, age, diet, sex, disease, and pharmaceuticals. A bone experiencing what would in some circumstances be seen as a stimulus to form more material could either be maintained at a constant level where circulating calcium was low, or the same loading could merely temper the amount of resorption experienced in an old person with a bone-wasting disease.
The elastic deformation of bone is measured in μStrain . [ 2 ] [ 3 ] 1000μStrain = 0.1% change of length of the bone.
It has to be considered that bone strength is highly dependent on geometry and direction of the acting forces in relation to this geometry. The fracture load for axial forces of the tibia for example is about 50 to 60 times the body weight. The fracture load for forces perpendicular to the axial direction is about 10 times lower.
Different types of bones can have different modeling and remodeling thresholds. The modeling threshold of the tibia is about 1500 μStrain (0.15% change of length), while the modeling threshold for parts of the bones of the skull is quite different. Some parts of the skull such as the lower jaw (mandible) experience significant forces and strains during chewing, but the dome of the cranium must remain strong to protect the brain, even if it does not experience what would be seen as stimulating strains. In one study where the strains were measured in the skull of a live human, it was shown that strains in the skull never exceeded 1/10 of the peak strain in the tibia of the same individual, with similar differences in strain rates. [ 8 ] This suggests that either bones of the skull are very sensitive to extremely low strains, or that the "genetic baseline" amount of bone in the skull in what is effectively disuse is not modified by the effects of loading. Whether the skulls of boxers are thicker than normal individuals is an intriguing question that has not been answered.
Since the physical, material properties of bone are not altered in the different bone types of the body, this difference in modeling threshold results in an increased bone mass and bone strength, thus in an increased safety factor (relation between fracture load and typical loads) for the skull compared to the tibia. A lower modeling threshold means that the same typical daily forces result in a ‘thicker’ and hence stronger bone at the skull.
Typical examples of the influence of maximum forces and the resulting elastic deformations on bone growth or bone loss are extended flights of astronauts and cosmonauts , as well as patients with paraplegia due to an accident. Extended periods in free fall do not lead to loss of bone from the skull, providing support to the idea that its bone is maintained by a genetic not a mechanical influence (skull bone often increases in long term space flights, something thought to be related to fluid shifts within the body).
A paraplegic patient in a wheelchair who is using his arms but not his legs will suffer massive muscle and bone loss in only his legs, due to the lack of usage of the legs. However, the muscles and bones of the arms which are used every day will stay the same, or might even increase, depending on the usage. [ 9 ]
The same effect can be observed for long flight astronauts or cosmonauts. [ 10 ] While they still use their arms in an almost normal manner, due to the lack of gravity in space there are no maximum forces induced on the bones of the legs. On earth, long term players of racquet sports experience similar effects, where the dominant arm can have 30% more bone than the other due to the asymmetric applications of force.
Harold Frost applied the Mechanostat model not only to skeletal tissues, but also to fibrous, collagenous connective tissues, such as ligaments, tendons, and fascia. [ 11 ] [ 12 ] He described their adaptational responsiveness to strain in his "stretch-hypertrophy rule":
Similar to the responsiveness of bony tissues, this adaptational response occurs only if the mechanical strain exceeds a certain threshold value. Harold Frost proposed that for dense, collagenous connective tissues, the related threshold value is around 4% strain elongation. [ 14 ] | https://en.wikipedia.org/wiki/Mechanostat |
Mechanosynthesis is a term for hypothetical chemical syntheses in which reaction outcomes are determined by the use of mechanical constraints to direct reactive molecules to specific molecular sites. There are presently no non-biological chemical syntheses which achieve this aim. Some atomic placement has been achieved with scanning tunnelling microscopes .
In conventional chemical synthesis or chemosynthesis , reactive molecules encounter one another through random thermal motion in a liquid or vapor. In a hypothesized process of mechanosynthesis, reactive molecules would be attached to molecular mechanical systems, and their encounters would result from mechanical motions bringing them together in planned sequences, positions, and orientations. It is envisioned that mechanosynthesis would avoid unwanted reactions by keeping potential reactants apart, and would strongly favor desired reactions by holding reactants together in optimal orientations for many molecular vibration cycles. In biology, the ribosome provides an example of a programmable mechanosynthetic device.
A non-biological form of mechanochemistry has been performed at cryogenic temperatures using scanning tunneling microscopes . [ 1 ] So far, such devices provide the closest approach to fabrication tools for molecular engineering . Broader exploitation of mechanosynthesis awaits more advanced technology for constructing molecular machine systems, with ribosome-like systems as an attractive early objective.
Much of the excitement regarding advanced mechanosynthesis regards its potential use in assembly of molecular-scale devices . Such techniques appear to have many applications in medicine, aviation, resource extraction, manufacturing and warfare.
Most theoretical explorations of advanced machines of this kind have focused on using carbon , because of the many strong bonds it can form, the many types of chemistry these bonds permit, and utility of these bonds in medical and mechanical applications. Carbon forms diamond, for example, which if cheaply available, would be an excellent material for many machines.
It has been suggested, notably by K. Eric Drexler , that mechanosynthesis will be fundamental to molecular manufacturing based on nanofactories capable of building macroscopic objects with atomic precision. The potential for these has been disputed, notably by Nobel Laureate Richard Smalley (who proposed and then critiqued an unworkable approach based on " Smalley fingers "). [ 2 ]
The Nanofactory Collaboration, [ 3 ] founded by Robert Freitas and Ralph Merkle in 2000, is a focused ongoing effort involving 23 researchers from 10 organizations and 4 countries that is developing a practical research agenda [ 4 ] specifically aimed at positionally controlled diamond mechanosynthesis and diamondoid nanofactory development.
In practice, getting exactly one molecule to a known place on the microscope's tip is possible, but has proven difficult to automate. Since practical products require at least several hundred million atoms, this technique has not yet proven practical in forming a real product.
The goal of one line of mechanoassembly research focuses on overcoming these problems by calibration, and selection of appropriate synthesis reactions. Some suggest attempting to develop a specialized, very small (roughly 1,000 nanometers on a side) machine tool that can build copies of itself using mechanochemical means, under the control of an external computer. In the literature, such a tool is called an assembler or molecular assembler. Once assemblers exist, geometric growth (directing copies to make copies) could reduce the cost of assemblers rapidly. Control by an external computer should then permit large groups of assemblers to construct large, useful projects to atomic precision. One such project would combine molecular-level conveyor belts with permanently mounted assemblers to produce a factory.
In part to resolve this and related questions about the dangers of industrial accidents and popular fears of runaway events equivalent to Chernobyl and Bhopal disasters, and the more remote issue of ecophagy , grey goo and green goo (various potential disasters arising from runaway replicators, which could be built using mechanosynthesis) the UK Royal Society and UK Royal Academy of Engineering in 2003 commissioned a study to deal with these issues and larger social and ecological implications, led by mechanical engineering professor Ann Dowling. This was anticipated by some to take a strong position on these problems and potentials —– and suggest any development path to a general theory of so-called mechanosynthesis. However, the Royal Society's nanotech report did not address molecular manufacturing at all, except to dismiss it along with grey goo.
Current technical proposals for nanofactories do not include self-replicating nanorobots, and recent ethical guidelines would prohibit development of unconstrained self-replication capabilities in nanomachines. [ 5 ] [ 6 ]
There is a growing body of peer-reviewed theoretical work on synthesizing diamond by mechanically removing/adding hydrogen atoms [ 7 ] and depositing carbon atoms [ 8 ] [ 9 ] [ 10 ] [ 11 ] [ 12 ] [ 13 ] (a process known as diamond mechanosynthesis or DMS [ 14 ] ).
For example, the 2006 paper in this continuing research effort by Freitas, Merkle and their collaborators reports that the most-studied mechanosynthesis tooltip motif (DCB6Ge) successfully places a C 2 carbon dimer on a C(110) diamond surface at both 300 K (room temperature) and 80 K ( liquid nitrogen temperature), and that the silicon variant (DCB6Si) also works at 80 K but not at 300 K. These tooltips are intended to be used only in carefully controlled environments (e.g., vacuum). Maximum acceptable limits for tooltip translational and rotational misplacement errors are reported in paper III—tooltips must be positioned with great accuracy to avoid bonding the dimer incorrectly. Over 100,000 CPU hours were invested in this study.
The DCB6Ge tooltip motif, initially described at a Foresight Conference in 2002, was the first complete tooltip ever proposed for diamond mechanosynthesis and remains the only tooltip motif that has been successfully simulated for its intended function on a full 200-atom diamond surface. Although an early paper gives a predicted placement speed of 1 dimer per second for this tooltip, this limit was imposed by the slow speed of recharging the tool using an inefficient recharging method [ 10 ] and is not based on any inherent limitation in the speed of use of a charged tooltip. Additionally, no sensing means was proposed for discriminating among the three possible outcomes of an attempted dimer placement—deposition at the correct location, deposition at the wrong location, and failure to place the dimer at all—because the initial proposal was to position the tooltip by dead reckoning, with the proper reaction assured by designing appropriate chemical energetics and relative bond strengths for the tooltip-surface interaction.
More recent theoretical work [ 15 ] analyzes a complete set of nine molecular tools made from hydrogen, carbon and germanium able to (a) synthesize all tools in the set (b) recharge all tools in the set from appropriate feedstock molecules and (c) synthesize a wide range of stiff hydrocarbons (diamond, graphite, fullerenes, and the like). All required reactions are analyzed using standard ab initio quantum chemistry methods.
Further research [ 16 ] to consider alternate tips will require time-consuming computational chemistry and difficult laboratory work.
In the early 2000s, a typical experimental arrangement was to attach a molecule to the tip of an atomic force microscope , and then use the microscope's precise positioning abilities to push the molecule on the tip into another on a substrate. Since the angles and distances can be precisely controlled, and the reaction occurs in a vacuum, novel chemical compounds and arrangements are possible.
The technique of moving single atoms mechanically was proposed by Eric Drexler in his 1986 book The Engines of Creation .
In 1989, researchers at IBM 's Zürich Research Institute successfully spelled the letters "IBM" in xenon atoms on a cryogenic copper surface, grossly validating the approach. [ 1 ] [ 17 ] Since then, a number of research projects have undertaken to use similar techniques to store computer data in a compact fashion. More recently the technique has been used to explore novel physical chemistries, sometimes using lasers to excite the tips to particular energy states, or examine the quantum chemistry of particular chemical bonds.
In 1999, an experimentally proved methodology called feature-oriented scanning [ 18 ] [ 19 ] (FOS) was suggested. The feature-oriented scanning methodology allows precisely controlling the position of the probe of a scanning probe microscope (SPM) on an atomic surface at room temperature. The suggested methodology supports fully automatic control of single- and multiprobe instruments in solving tasks of mechanosynthesis and bottom-up nanofabrication .
In 2003, Oyabu et al. [ 20 ] reported the first instance of purely mechanical-based covalent bond-making and bond-breaking, i.e., the first experimental demonstration of true mechanosynthesis—albeit with silicon rather than carbon atoms.
In 2005, the first patent application on diamond mechanosynthesis [ 21 ] was filed.
In 2008, a $3.1 million grant was proposed [ 22 ] to fund the development of a proof-of-principle mechanosynthesis system.
In 2013, IBM made A Boy and His Atom , a short animated film using atoms. [ 23 ]
See also molecular nanotechnology , a more general explanation of the possible products, and discussion of other assembly techniques. | https://en.wikipedia.org/wiki/Mechanosynthesis |
In cellular biology , mechanotransduction ( mechano + transduction ) is any of various mechanisms by which cells convert mechanical stimulus into electrochemical activity. [ 1 ] [ 2 ] [ 3 ] [ 4 ] This form of sensory transduction is responsible for a number of senses and physiological processes in the body, including proprioception , touch , [ 5 ] balance , and hearing . [ 6 ] [ 7 ] [ 8 ] The basic mechanism of mechanotransduction involves converting mechanical signals into electrical or chemical signals .
In this process, a mechanically gated ion channel makes it possible for sound, pressure, or movement to cause a change in the excitability of specialized sensory cells and sensory neurons . [ 9 ] The stimulation of a mechanoreceptor causes mechanically sensitive ion channels to open and produce a transduction current that changes the membrane potential of the cell. [ 10 ] Typically the mechanical stimulus gets filtered in the conveying medium before reaching the site of mechanotransduction. [ 11 ] Cellular responses to mechanotransduction are variable and give rise to a variety of changes and sensations. Broader issues involved include molecular biomechanics .
Single-molecule biomechanics studies of proteins and DNA, and mechanochemical coupling in molecular motors have demonstrated the critical importance of molecular mechanics as a new frontier in bioengineering and life sciences. Protein domains, connected by intrinsically disordered flexible linker domains, induce long-range allostery via protein domain dynamics .
The resultant dynamic modes cannot be generally predicted from static structures of either the entire protein or individual domains. They can however be inferred by comparing different structures of a protein (as in Database of Molecular Motions ). They can also be suggested by sampling in extensive molecular dynamics trajectories [ 12 ] and principal component analysis, [ 13 ] or they can be directly observed using spectra [ 14 ] [ 15 ] measured by neutron spin echo spectroscopy. Current findings indicate that the mechanotransduction channel in hair cells is a complex biological machine . Mechanotransduction also includes the use of chemical energy to do mechanical work. [ 16 ]
Air pressure changes in the ear canal cause the vibrations of the tympanic membrane and middle ear ossicles . At the end of the ossicular chain, movement of the stapes footplate within the oval window of the cochlea generates a pressure field within the cochlear fluids, imparting a pressure differential across the basilar membrane . A sinusoidal pressure wave results in localized vibrations of the organ of Corti : near the base for high frequencies, near the apex for low frequencies. [ 17 ] Hair cells in the cochlea are stimulated when the basilar membrane is driven up and down by differences in the fluid pressure between the scala vestibuli and scala tympani . This motion is accompanied by a shearing motion between the tectorial membrane and the reticular lamina of the organ of Corti, causing the hair bundles that link the two to be deflected, initiating mechano-electrical transduction. When the basilar membrane is driven upward, shear between the hair cells and the tectorial membrane deflects hair bundles in the excitatory direction, toward their tall edge. At the midpoint of an oscillation the hair bundles resume their resting position. When the basilar membrane moves downward, the hair bundles are driven in the inhibitory direction. [ 18 ]
When a deformation is imposed on a muscle, changes in cellular and molecular conformations link the mechanical forces with biochemical signals, and the close integration of mechanical signals with electrical, metabolic, and hormonal signaling may disguise the aspect of the response that is specific to the mechanical forces. [ 19 ]
One of the main mechanical functions of articular cartilage is to act as a low-friction, load-bearing surface. Due to its unique location at joint surfaces, articular cartilage experiences a range of static and dynamic forces that include shear, compression and tension. These mechanical loads are absorbed by the cartilage extracellular matrix (ECM), where they are subsequently dissipated and transmitted to chondrocytes (cartilage cells).
Chondrocytes sense and convert the mechanical signals they receive into biochemical signals, which subsequently direct and mediate both anabolic (matrix building) and catabolic (matrix degrading) processes. These processes include the synthesis of matrix proteins ( type II collagen and proteoglycans ), proteases , protease inhibitors, transcription factors , cytokines and growth factors . [ 20 ] [ 21 ]
The balance that is struck between anabolic and catabolic processes is strongly influenced by the type of loading that cartilage experiences. High strain rates (such as which occurs during impact loading) cause tissue damage, degradation, decreased matrix production and apoptosis . [ 22 ] [ 23 ] Decreased mechanical loading over long periods, such as during extended bed-rest, causes a loss of matrix production. [ 24 ] Static loads have been shown to be detrimental to biosynthesis [ 25 ] while oscillatory loads at low frequencies (similar that of a normal walking gait) have been shown to be beneficial in maintaining health and increasing matrix synthesis. [ 26 ] Due to the complexity of in-vivo loading conditions and the interplay of other mechanical and biochemical factors, the question of what an optimal loading regimen may be or whether one exists remain unanswered.
Although studies have shown that, like most biological tissues, cartilage is capable of mechanotransduction, the precise mechanisms by which this is done remain unknown. However, there exist a few hypotheses which begin with the identification of mechanoreceptors . [ citation needed ]
In order for mechanical signals to be sensed, there need to be mechanoreceptors on the surface of chondrocytes. Candidates for chondrocyte mechanoreceptors include stretch-activated ion channels (SAC), [ 27 ] the hyaluronan receptor CD44 , annexin V (a collagen type II receptor), [ 28 ] and integrin receptors (of which there exist several types on chondrocytes).
Using the integrin-linked mechanotransduction pathway as an example (being one of the better studied pathways), it has been shown to mediate chondrocyte adhesion to cartilage surfaces, [ 29 ] mediate survival signaling [ 30 ] and regulate matrix production and degradation. [ 31 ]
Integrin receptors have an extracellular domain that binds to the ECM proteins (collagen, fibronectin , laminin , vitronectin and osteopontin ), and a cytoplasmic domain that interacts with intracellular signaling molecules. When an integrin receptor binds to its ECM ligand and is activated, additional integrins cluster around the activated site. In addition, kinases (e.g., focal adhesion kinase , FAK) and adapter proteins (e.g., paxillin , aka Pax, talin , aka Tal, and Shc ) are recruited to this cluster, which is called the focal adhesion complex (FAC). The activation of these FAC molecules in turn, triggers downstream events that up-regulate and /or down-regulate intracellular processes such as transcription factor activation and gene regulation resulting in apoptosis or differentiation. [ citation needed ]
In addition to binding to ECM ligands, integrins are also receptive to autocrine and paracrine signals such as growth factors in the TGF-beta family. Chondrocytes have been shown to secrete TGF-b, and upregulate TGF-b receptors in response to mechanical stimulation; this secretion may be a mechanism for autocrine signal amplification within the tissue. [ 32 ]
Integrin signaling is just one example of multiple pathways that are activated when cartilage is loaded. Some intracellular processes that have been observed to occur within these pathways include phosphorylation of ERK1/2, p38 MAPK, and SAPK/ERK kinase-1 (SEK-1) of the JNK pathway [ 33 ] as well as changes in cAMP levels, actin re-organization and changes in the expression of genes which regulate cartilage ECM content. [ 34 ]
More recent studies have hypothesized that chondrocyte primary cilium act as a mechanoreceptor for the cell, transducing forces from the extracellular matrix into the cell. Each chondrocyte has one cilium and it is hypothesized to transmit mechanical signals by way of bending in response to ECM loading. Integrins have been identified on the upper shaft of the cilium, acting as anchors to the collagen matrix around it. [ 35 ] Recent studies published by Wann et al. in FASEB Journal have demonstrated for the first time that primary cilia are required for chondrocyte mechanotransduction. Chondrocytes derived from IFT88 mutant mice did not express primary cilia and did not show the characteristic mechanosensitive up regulation of proteoglycan synthesis seen in wild type cells [ 36 ]
It is important to examine the mechanotransduction pathways in chondrocytes since mechanical loading conditions which represent an excessive or injurious response upregulates synthetic activity and increases catabolic signalling cascades involving mediators such as NO and MMPs. In addition, studies by Chowdhury TT and Agarwal S have shown that mechanical loading which represents physiological loading conditions will block the production of catabolic mediators (iNOS, COX-2, NO, PGE2) induced by inflammatory cytokines (IL-1) and restore anabolic activities. Thus an improved understanding of the interplay of biomechanics and cell signalling will help to develop therapeutic methods for blocking catabolic components of the mechanotransduction pathway. A better understanding of the optimal levels of in vivo mechanical forces are therefore necessary for maintaining the health and viability of cartilage, preventative techniques may be devised for the prevention of cartilage degradation and disease. [ citation needed ] | https://en.wikipedia.org/wiki/Mechanotransduction |
Mecillinam ( INN ) or amdinocillin ( USAN ) is an extended-spectrum penicillin antibiotic of the amidinopenicillin class that binds specifically to penicillin binding protein 2 (PBP2), [ 2 ] and is only considered to be active against Gram-negative bacteria . It is used primarily in the treatment of urinary tract infections , and has also been used to treat typhoid and paratyphoid fever . [ 3 ] [ 4 ] Because mecillinam has very low oral bioavailability , an orally active prodrug was developed: pivmecillinam .
Mecillinam is used in the treatment of infections due to susceptible gram-negative bacteria, especially urinary tract infections which are most commonly caused by Escherichia coli . [ 5 ] Mecillinam is active against most pathogenic Gram-negative bacteria, except Pseudomonas aeruginosa and some species of Proteus . [ 6 ] Several studies have also found it to be as effective as other antibiotics for treating Staphylococcus saprophyticus infection, though it is Gram-positive, possibly because mecillinam reaches very high concentrations in urine. [ 1 ]
Worldwide resistance to mecillinam in bacteria causing urinary tract infection has remained very low since its introduction; a 2003 study conducted in 16 European countries and Canada found resistance to range from 1.2% ( Escherichia coli ) to 5.2% ( Proteus mirabilis ). [ 7 ] Another large study conducted in Europe and Brazil obtained similar results — 95.9% of E. coli strains, for instance, were sensitive to mecillinam. [ 8 ]
The adverse effect profile of mecillinam is similar to that of other penicillins. [ 2 ] Its most common side effects are rash and gastrointestinal upset, including nausea and vomiting . [ 1 ]
With the codename FL 1060, mecillinam was developed by the Danish pharmaceutical company Leo Pharmaceutical Products (now LEO Pharma ). It was first described in the scientific literature in a 1972 paper. [ 9 ] [ 10 ] | https://en.wikipedia.org/wiki/Mecillinam |
The Mecke reagent is used as a simple spot-test to presumptively identify alkaloids as well as other compounds. It is composed of a mixture of selenous acid and concentrated sulfuric acid , [ 1 ] which is dripped onto the substance being tested.
The United States Department of Justice method for producing the reagent is the addition of 100 mL of concentrated (95–98%) sulfuric acid to 1 g of selenous acid. While sale to the general public is legal, it is not recommended as strong corrosives can cause permanent skin and eye damage and require extensive safety ratings. [ 2 ]
This article about analytical chemistry is a stub . You can help Wikipedia by expanding it . | https://en.wikipedia.org/wiki/Mecke_reagent |
The Meco-Moore cutter loader was an early twentieth-century British mining machine. It was invented by Mr M. Moore, and developed by the Mining Engineering Company (MECO) of Worcester . It was a heavy machine (120 hp / 89.5 kW) and was first used in a coal mine in Lancashire, England 1934. [ 1 ] The design was such that it worked along the coal seam (along a "longwall panel") The machine's cutter bars, the "jibs" as they were called, (two in the original model and three in a later versions) were designed to both shear and undercut the coal seam. The cut coal was cut onto the connected conveyor belt system which took it towards the mine's entrance. It was, or was among, the first such machines to do both cutting and loading at the same time. The machine increased both productivity and safety. [ 2 ] | https://en.wikipedia.org/wiki/Meco-Moore_Cutter_Loader |
MedChemComm (in full: Medicinal Chemistry Communications ) is a peer-reviewed scientific journal publishing original (primary) research and review articles on all aspects of medicinal chemistry , including drug discovery , pharmacology and pharmaceutical chemistry . Until December 2019, it was published monthly by the Royal Society of Chemistry in partnership with the European Federation for Medicinal Chemistry , of which it was the official journal. Authors can elect to have accepted articles published as open access . [ 1 ] According to the Journal Citation Reports , the journal has a 2014 impact factor of 2.495, ranking it 27th out of 59 journals in the category "Chemistry, Medicinal" [ 2 ] and 163 out of 289 journals in the category "Biochemistry & Molecular Biology". [ 3 ]
The editor-in-chief is Mike Waring ( Newcastle University ). [ 4 ]
As of January 1, 2020 - the journal is now called RSC Medicinal Chemistry and continues to be published monthly under this new name. [ 5 ]
MedChemComm publishes Research Articles (original scientific work, usually between 4-10 pages in length) and Reviews (critical analyses of specialist areas). | https://en.wikipedia.org/wiki/MedChemComm |
The Medal "For the Tapping of the Subsoil and Expansion of the Petrochemical Complex of Western Siberia" ( Russian : Медаль «За освоение недр и развитие нефтегазового комплекса Западной Сибири» ) was a civilian award of the Soviet Union established on July 28, 1978 by Decree of the Presidium of the Supreme Soviet of the USSR [ 1 ] to recognise three years of dedicated work in developing the Petrochemical Complex of Western Siberia .
The Medal "For the Tapping of the Subsoil and Expansion of the Petrochemical Complex of Western Siberia" was awarded to active members in the underground exploration and development of the oil and gas complex of Western Siberia for selfless labour in the identification, exploration and development of the mining and industrial processing of oil and gas, for work in construction, in manufacturing, in housing and other civilian facilities, in building highways, in electricity, transport or other services to the oil and gas industries, as well as to employees of scientific, research or design organizations, of institutions and organizations, of the service sector, Party, Soviet, trade union or Komsomol organs of the oil and gas industry, who produced conscientious work and contributed to the development of the petrochemical complex of Western Siberia over a period of at least three years. [ 1 ]
Recommendations for award of the Medal "For the Tapping of the Subsoil and Expansion of the Petrochemical Complex of Western Siberia" were made by the administrative heads of enterprises, institutions, organizations, party, trade union or Komsomol organizations or labour collectives and the executive committees of the District or City Council of People's Deputies. The names of the potential recipients were then forwarded to the various ministries and agencies overseeing the different companies and organisations which were working in the development of the petrochemical complex of Western Siberia for approval. The names of the recipients was then forwarded to the executive committees of the Tyumen or Tomsk oblasts Soviets of People's Deputies for award on behalf of the Presidium of the Supreme Soviet of the USSR and of the Presidium of the Supreme Soviet of the RSFSR . [ 1 ]
The Medal "For the Tapping of the Subsoil and Expansion of the Petrochemical Complex of Western Siberia" was worn on the left side of the chest and in the presence of other medals of the USSR, immediately after the Medal "For Transforming the Non-Black Earth of the RSFSR" . If worn in the presence of awards of the Russian Federation, the latter have precedence. [ 2 ]
Each medal came with an attestation of award, this attestation came in the form of a small 8 cm by 11 cm cardboard booklet bearing the award's name, the recipient's particulars and an official stamp and signature on the inside. [ 1 ]
The Medal "For the Tapping of the Subsoil and Expansion of the Petrochemical Complex of Western Siberia" was a 32 mm in diameter circular brass medal. On its obverse , in the right half, the relief image of a sickle over a vertical hammer, in the background, the relief images of two oil rigs at center, two gas tanks at left, a tractor and piping at lower center, at the bottom a small relief five pointed star, along the medal circumference, the relief inscription "For the tapping of the subsoil and expansion of the petrochemical complex of Western Siberia" ( Russian : «За освоение недр и развитие нефтегазового комплекса Западной Сибири» ). On the reverse, in the central upper half, a relief five pointed star emitting rays from between its arms forming an inversed pentagon, superimposed over the star, the relief inscription "USSR" ( Russian : «СССР» ), at the bottom, crossed laurel and oak branches. [ 1 ]
The Medal "For the Tapping of the Subsoil and Expansion of the Petrochemical Complex of Western Siberia" was secured to a standard Soviet pentagonal mount by a ring through the medal suspension loop. The mount was covered by a 24 mm wide overlapping green silk moiré ribbon with a 6 mm wide central blue stripe bordered on both sides by 2 mm black stripes themselves bordered on the outside by 1 mm wide white stripes. [ 1 ]
The individuals below were recipients of the Medal "For the Tapping of the Subsoil and Expansion of the Petrochemical Complex of Western Siberia". | https://en.wikipedia.org/wiki/Medal_"For_the_Tapping_of_the_Subsoil_and_Expansion_of_the_Petrochemical_Complex_of_Western_Siberia" |
The Medea hypothesis is a term coined by paleontologist Peter Ward [ 1 ] for a hypothesis that contests the Gaian hypothesis and proposes that multicellular life , understood as a superorganism , may be self-destructive or suicidal.
The metaphor refers to the mythological Medea (representing the Earth), who kills her own children (multicellular life).
In this view, microbial-triggered mass extinctions result in returns to the microbial-dominated state Earth has been in for most of its history. [ 2 ] [ 3 ] [ 4 ]
Possible examples of extinction events induced entirely or partially by biotic activities include:
The list excludes the Cretaceous–Paleogene extinction event , since this was, at least partially, externally induced by a meteor impact .
Peter Ward proposes that the current man-made climate change and mass extinction event may be considered to be the most recent Medean event. As these events are anthropogenic, he postulates that Medean events are not necessarily caused by microbes, but by intelligent life as well and that the final mass extinction of complex life, roughly about 500–900 million years in the future, can also be considered a Medean event: "Plant life that still exists then will be forced to adapt to a warming and expanding Sun, causing them to remove even more carbon dioxide from the atmosphere (which in turn will have already been lowered due to the increasing heat from the Sun gradually speeding up the weathering process that removes these molecules from the atmosphere), and ultimately accelerating the complete extinction of complex life by making carbon dioxide levels drop down to just 10 ppm , below which plants can no longer survive." However, Ward simultaneously argues that intelligent life such as humans may not necessarily just trigger future Medean events, but may eventually prevent them from occurring. [ citation needed ] | https://en.wikipedia.org/wiki/Medea_hypothesis |
Media Independent Handover ( MIH ) is a standard being developed by IEEE 802.21 to enable the handover of IP sessions from one layer 2 access technology to another, to achieve mobility of end user devices (MIH).
The importance of MIH derives from the fact that a diverse range of broadband wireless access technologies is available and in course of development, including GSM , UMTS , CDMA2000 , WiMAX , Mobile-Fi and WPANs. Multimode wireless devices that incorporate more than one of these wireless interfaces require the ability to switch among them during the course of an IP session, and devices such as laptops with Ethernet and wireless interfaces need to switch similarly between wired and wireless access.
Handover may be required, e.g. because a mobile device experiences a degradation in the radio signal, or because an access point experiences a heavy traffic load.
The key functionality provided by MIH is communication among the various wireless layers and between them and the IP layer. The required messages are relayed by the Media Independent Handover Function, MIHF, that is located in the protocol stack between the layer 2 wireless technologies and IP at layer 3. MIH may communicate with various IP protocols including Session Initiation Protocol (SIP) for signaling, Mobile IP for mobility management, and DiffServ and IntServ for quality of service (QoS).
When a session is handed off from one access point to another access point using the same technology, the handover can usually be performed within that wireless technology itself without involving MIHF or IP. For instance a VoIP call from a Wi-Fi handset to a Wi-Fi access point can be handed over to another Wi-Fi access point within the same network, e.g. a corporate network, using Wi-Fi standards such as 802.11f and 802.11r . However, if the handover is from a Wi-Fi access point in a corporate network to a public Wi-Fi hotspot, then MIH is required, since the two access points cannot communicate with each other at the link layer, and are, in general, on different IP subnets.
When a session is handed off from one wireless technology to another, MIH may assist the handover process by exchanging messages among the Internet access technologies and IP. Message are of three types:
• Event notifications are passed from a lower layer in the protocol stack to a higher layer or between the MIHF of one device to the MIHF of another device. For instance “wireless link quality is degrading” is an event notification that is passed from the wireless layer to the MIHF layer.
• Commands are passed down the protocol stack or between the MIHF of one device to the MIHF of another device. For instance “Initiate Handover” is a command in which the access point MIHF provides the mobile device MIHF with a list of alternative access points that it could use.
• Information Service is of three types. A higher layer may request information from a lower layer, e.g. the MIHF may request performance information, such as delay from the wireless layer. A lower layer may request information from a higher layer, e.g. the MIHF may request to know the ISP Name from the IP layer. One MIHF may request information from another MIHF, e.g. the availability of location-based services.
The MIH function, MIHF, is implemented:
• in mobile devices that have more than one wireless/wired interface;
• in access points that have at least one wireless interface;
• in core network equipment that may have no wireless interface.
Mobile devices and access points clearly need to implement MIHF in order to communicate in a standard way between each other and between the wireless and IP layers. This allows them to make their own local decisions as to whether and how to handover a session. The reason for MIHF in core network equipment with no wireless interface is to enable the design of “handover servers” which can make centralized decisions about the handover of sessions among multiple access points and multiple access technologies. Such servers allow a wireless network operator to balance the traffic load so as to alleviate congestion on specific access points, and deliver sufficient QoS to all users.
Short-lived sessions such as accessing a single web page typically do not require handover or QoS. Longer duration sessions, which may well require handover, such as VoIP, audio/video streaming (including live TV and VoD), and VPNs , typically have QoS requirements including delay, delay variation and packet loss.
It is important that QoS is maintained, not just before and after a handover, but also during the handover, and this can be achieved by using MIH to plan ahead. Before a handover is required, the MIHFs communicate to identify which access points using which wireless technologies are within range and what QoS is available from them. MIH can also be used to pre-authenticate the mobile device with alternative potential access points and to reserve capacity prior to handover. For instance WiMAX allows resources to be reserved for a session before they are actually allocated to that session. When a handover becomes necessary, much of the ground-work is therefore already in place and the session can be handed over with minimal delay and packet loss. Incoming packets to the mobile device that are delivered to the old access point after the handover can be forwarded via the new access point, thus further reducing packet loss.
QoS is handled differently by each technology, including both the wireless access technologies and also IP, which has two QoS approaches, DiffServ and IntServ . Some technologies divide traffic into “Service Classes”, e.g. streaming, while others allow users to specify quantitative “QoS Parameters”, e.g. transfer delay. WiFi , Mobile-Fi and DiffServ use the service class approach and although they do not have exactly the same service classes, it is possible to make a correspondence among them. WiMAX and IntServ use the QoS parameter approach, and UMTS uses both approaches. Again correspondences among parameters can be made, [1].
MIH can be used to exchange information about service class and QoS parameter availability from one wireless technology to another and to the IP layer. One source of such information is performance measurements made by the wireless layer, e.g. 802.11k for WiFi and 802.16f for WiMAX .
To illustrate the operation of MIH, let us take an example of a real-time gaming application, using DiffServ at the IP layer, being handed over from Mobile-Fi to WiMAX . The application is currently using the Assured Forwarding Class 1, AF1, DiffServ service, and the Class 2 Real-Time Interactive Mobile-Fi service.
Since the MIH standard is not yet finalized, this example is illustrative of the type of functionality that may be provided, as opposed to a firm guarantee of what will become available. Also the standard specifies the MIH messages. The use of those messages in any particular application is implementation dependent. The example below is for illustrative purposes only.
1. The mobile device notices a degradation in the Mobile-Fi wireless signal strength and uses the MIH Event Notification Service to inform the MIHF layer in the mobile device. This information is passed to the MIHF in the access point.
2. The access point uses the MIH Command Service to tell the mobile device to initiate handover and includes a list of potential access points.
3. The mobile device MIHF passes this list to its various wireless layers and, using the MIH Information Service, requests them to determine the signal strength of each access point and report back to the MIHF.
4. The MIHF in the mobile device determines that the best signal strength comes from a WiMAX access point, and passes that information to its IP layer, using the Event Notification Service.
5. DiffServ at the IP layer in the mobile device uses the Information Service to request performance information from the WiMAX access point. This request is passed through the mobile device MIHF, via the WiMAX access point MIHF, to the WiMAX access point wireless layer.
6. The WiMAX layer in the access point uses IEEE 802.16f to obtain the performance information and reports back that it can schedule the session using its Unsolicited Grant Service, UGS, with a link delay of 5 ms, or on its Real-Time Polling Service with a link delay of 18 ms.
7. DiffServ selects the WiMAX UGS, and uses the MIH Command Service to tell the mobile device to commit to handover. It may also use Mobile IP if a change in the mobile device IP address is required.
Another standard that can be used for handover from one wireless technology to another is UMA, Unlicensed Mobile Access , which provides handover between WiFi and GSM/GPRS/ UMTS . It was originally developed by an independent industry consortium and was incorporated into the 3GPP standards in 2005 under the name GAN (Generic Access Network).
Another standard of interest is 802.11u which provides roaming between 802.11 networks and other networks, so that services from one network can be accessed when the user is subscribed to services from another network. However it does not provide handover of IP sessions in progress.
David J Wright; Maintaining QoS During Handover Among Multiple Wireless Access Technologies, International Conference on Mobile Commerce, Toronto, July 2007.
Ok Sik Yang; Seong Gon Choi; Jun Kyun Choi; Jung Soo Park; Hyoung Jun Kim;
A handover framework for seamless service support between wired and wireless networks, Advanced Communication Technology, 2006. ICACT 2006. The 8th International Conference, Volume 3, 20-22 Feb. 2006 Page(s):6 pp.
Al Mosawi, T.; Wisely, D.; Aghvami, H.; A Novel Micro Mobility Solution Based on Media Independent Handover and SIP, Vehicular Technology Conference, 2006. VTC-2006 Fall.2006 IEEE 64th, Sept. 2006 Page(s):1 - 5
Yoon Young An; Byung Ho Yae; Kang Won Lee; You Ze Cho; Woo Young Jung; Reduction of Handover Latency Using MIH Services in MIPv6, Advanced Information Networking and Applications, 2006. AINA 2006. 20th International Conference on, Volume 2, 18-20 April 2006 Page(s):229 - 234 | https://en.wikipedia.org/wiki/Media-independent_handover |
Media on demand (MOD) is a new generation of video on demand which not only allows users to watch and listen to audio and video content such as movies and TV shows, but also provides facilities including real-time information, interactive games, attractions guidance, route information, advertising systems, and services for shopping and ordering. Users can select content whenever they want, rather than having to watch it at a specific broadcast time.
In the transportation industry, media-on-demand technology was first applied by FUNTORO , which offer media on demand as in-vehicle infotainment to bus and railway passengers through high-definition interactive monitors embedded in seatback or armrest. [ 1 ] [ 2 ] [ 3 ]
Some telecommunication companies offer media-on-demand service by transmitting a digital signal to a set-top box that is connected to a television screen or other display devices. Clients are typically required to pay a monthly fee to get access to a bundle of multimedia content. [ 4 ]
This article related to telecommunications is a stub . You can help Wikipedia by expanding it . | https://en.wikipedia.org/wiki/Media-on-demand |
MediaFLO was a technology developed by Qualcomm for transmitting audio, video and data to portable devices such as mobile phones and personal televisions, used for mobile television . Qualcomm operated a mobile pay television service, FLO TV , from 2007 to 2011 using this technology.
Broadcast data transmitted via MediaFLO includes live, real time audio and video streams, as well as scheduled video and audio clips and shows. The technology could also carry Internet Protocol datacast application data, such as stock market quotes, sports scores, and weather reports . [ 1 ]
In October 2010, Qualcomm announced it was suspending new sales of the service to consumers. [ 2 ] [ 3 ] In December 2010, AT&T announced that it will purchase Qualcomm's FCC licenses in the 700 MHz band. [ 4 ] FLO TV discontinued service on March 27, 2011.
Devices featuring MediaFLO were introduced by LG and Samsung at the 2006 Consumer Electronics Show . On December 1, 2005, Verizon Wireless and Qualcomm announced a partnership for the launch of the MediaFLO network. [ citation needed ]
MediaFLO-based pay TV services were first commercially offered on mobile phones . The service debuted on Verizon Wireless as V CAST Mobile TV in select cities on March 1, 2007, [ 5 ] [ 6 ] and rolled out nationwide throughout 2007 and 2008. [ 7 ] AT&T announced a similar service in February 2007, intended to launch later that year; following delays, AT&T's MediaFLO TV service launched on May 4, 2008. [ 8 ] [ 9 ] [ 10 ]
Qualcomm began selling FLO TV directly to consumers in November 2009 with the launch of the FLO TV Personal Television. [ 11 ] [ 12 ] [ 13 ] The Personal Television was manufactured by HTC , [ 14 ] and featured a 3.5" touchscreen. It retailed for US$249 at launch, and included a six-month FLO TV subscription; after the trial, a US$15 monthly subscription fee was required to use the service. [ 15 ] Later, in August 2010, Audiovox introduced a FLO TV-equipped portable DVD player , which retailed for US$199. [ 16 ] [ 17 ]
From 2009 to 2010, Audiovox produced FLO TV systems for automobiles. [ 18 ] [ 19 ] The automotive FLO TV system was introduced by Chrysler in December 2009, as a Mopar dealer-installed accessory on 2010-model vehicles equipped with the Video Entertainment System. [ 20 ] Chrysler also offered the FLO TV tuner as an aftermarket upgrade for 2008 and 2009-model vehicles sold with the system. [ 21 ] Chrysler offered FLO TV in addition to the competing Sirius Backseat TV service operated by Sirius Satellite Radio . [ 22 ] Audiovox, under its Advent brand, began selling third-party automotive FLO TV systems through aftermarket equipment dealers in February 2010. [ 18 ] [ 19 ]
In July 2010, Qualcomm CEO Paul Jacobs stated that the company was suffering financial losses operating FLO TV, [ 23 ] and planned to either sell MediaFLO or find a partner to continue its operation. [ 24 ] The company reportedly discussed possible collaboration with software developers on other uses of the MediaFLO spectrum, which they stated could include distribution of electronic magazines or newspapers. [ citation needed ] The company had predicted the total cost to launch the service would be $800 million, [ citation needed ] including the $683 million that Qualcomm reportedly paid for the spectrum. [ 25 ]
Qualcomm suspended sales of FLO TV to new customers on October 5, 2010, but stated that the service would remain available to existing customers through the spring of 2011. [ 26 ] On October 12, Qualcomm stated that FLO TV would shut down on March 27, 2011. [ 27 ] Qualcomm offered rebates to customers who purchased a FLO TV-equipped DVD player or Personal Television, which could be claimed until April 30, 2011. [ 27 ] Chrysler also announced plans to reimburse customers who purchased a FLO TV system, though the system was reportedly only purchased by 851 Chrysler customers. [ 22 ]
On December 20, 2010, AT&T announced that it would purchase Qualcomm's FCC licenses in the 700 MHz band for $1.93 billion. [ 25 ] [ 28 ] Despite spending $132 million in the previous quarter on bolstering FLO TV, Qualcomm still made a profit on the sale, as it had originally paid $38 million for the former channel 55 and $558 million for the former channel 56. [ 28 ]
Some trials were underway in Japan, Hong Kong and Taiwan, with no commitment for a commercial release. [ citation needed ] In France, Qualcomm tried unsuccessfully to convince TDF to adopt MediaFLO technology. [ citation needed ] In the UK, British Sky Broadcasting conducted trials of MediaFLO in 2006. [ citation needed ]
All U.S. MediaFLO providers offered a set of 14 basic channels:
Adult Swim time-shared with 2.FLO, as it does on cable TV with Cartoon Network . [ citation needed ] Additionally, the "FLO Preview Channel" was a free-to-view barker channel , available without subscription. [ 30 ]
Verizon offered those 14 channels, plus MTV Tres and TLC . [ 31 ] AT&T, Personal Television, and Automotive systems offered the base 14, plus CNN Live Mobile and Crackle. [ citation needed ]
The "FLO" in MediaFLO stood for Forward Link Only , [ 32 ] meaning that the data transmission path is one way, from the tower to the device. The MediaFLO system transmitted data on a frequency separate from the frequencies used by current mobile telephone networks. In the United States , the MediaFLO system used frequency spectrum 716-722 MHz, which had previously been allocated to UHF TV channel 55 .01Nov2004 Qualcomm press release regarding 700 MHz spectrum usage for MediaFLO [ 33 ]
FLO was standardized within ETSI as TS 102 589, [ 34 ] and has components standardized within the Telecommunications Industry Association (TIA 1099, 1102, 1103, 1104, 1120, 1130, 1132, 1146 and 1178.)
MediaFLO was a competitor to the Korean T-DMB , the Japanese 1seg and the European DVB-H standards.
Qualcomm conducted MediaFLO technical trials internationally, with the intention of forming partnerships with existing multi-channel content providers and service operators, but has since discontinued development.
The protocol was developed because of the inherent spectral inefficiency of unicasting high-rate full-motion video to multiple subscribers. Additionally, traditional analog television and over-the-air terrestrial digital television signals ( DVB-T ) were difficult to implement on mobile devices, due mostly to issues of power consumption . ATSC , used only by the United States and its neighbors, also has difficulty even with fixed reception due to multipath , and mobile ATSC-M/H (which is free-to-air from individual TV stations ) was not finalized until 2008.
In addition, the transmission need not convey as high a resolution as would be needed for a larger display. MediaFLO streams are only 200-250 kbit/s, which would be insufficient for a larger screen size. [ 35 ]
In the now defunct United States implementation, FLO was transmitted by a network of high-power broadcast transmitters operating at effective radiated powers as high as 50 kilowatts. This allowed for a coverage area of a transmitter to be as large as 30 to 40 kilometres (19 to 25 mi). [ 36 ] The activation of many of these transmitters were delayed due to the official end of analog TV broadcasting on channel 55 being delayed . [ 37 ] Immediately following the transition, the FLO network was expanded to several new markets, and coverage was enhanced in some existing ones. [ 38 ]
The transmission was an encrypted OFDM set of QAM signals sent on a 5.55 MHz channel from 716-722 MHz (former UHF TV channel 55 ). The band was auctioned -off by the Federal Communications Commission (FCC) and known as the "Lower 700 MHz Block D". [ 39 ] Qualcomm also bought, in a later auction, the use of former analog UHF TV channel 56 (722-728 MHz) in Boston, Los Angeles, New York, Philadelphia and San Francisco for additional services. However, this is owned by Manifest Wireless (a subsidiary of Dish Network 's Frontier Wireless) in most other media markets , where ATSC-M/H signals were on air . All of the transmitters sent the same signal and used the same frequency, forming a single-frequency network . This allowed the mobile to decode the signal from more than one transmitter in the same way that it might if it was a multipath -delayed version from the same transmitter. [ 36 ] All stations used callsign WPZA237 , but each has an identifier indicating its group and number. For example, one station in the metro Atlanta media market was ATL-006, while another was ATL-014.
Some other operational parameters of MediaFLO are as follows:
[ 36 ]
All of the bearer (data) traffic occurred within an MLC using the 3500 non-overhead subcarriers. The protocol also contemplates a certain amount of inter-symbol time spacing, to allow for the effects of multi-path transmission and reception.
[ 36 ]
There is a window time T WGI included both before and after each OFDM symbol. However, since this window is shared between each two consecutive symbols, T S = T U + T WGI + T FGI .
For conditional access , Verizon Wireless utilized its EVDO network to authenticate mobile handsets and provide the decryption keys necessary to decode the programming. Because of this, users who block data use to prevent unauthorized charge were also blocked from viewing any channels, including the preview channel. [ citation needed ] | https://en.wikipedia.org/wiki/MediaFLO |
The Media Object Server ( MOS ) protocol allows newsroom computer systems (NRCS) to communicate using a standard protocol with video servers , audio servers , still stores , and character generators for broadcast production. [ 1 ] [ 2 ]
The MOS protocol is based on XML . [ 3 ] It enables the exchange of the following types of messages: [ 4 ]
MOS was developed to reduce the need for the development of device specific drivers . By allowing developers to embed functionality and handle events, vendors were relieved of the burden of developing device drivers. It was left to the manufacturers to interface newsroom computer systems. This approach affords broadcasters flexibility to purchase equipment from multiple vendors. [ 5 ] It also limits the need to have operators in multiple locations throughout the studio as, for example, multiple character generators (CG) can be fired from a single control workstation , without needing an operator at each CG console. [ 6 ]
MOS enables journalists to see, use, and control media devices inside Associated Press 's ENPS system so that individual pieces of newsroom production technology speak a common XML -based language. [ 7 ]
The first meeting of the MOS protocol development group occurred at the Associated Press ENPS developer's conference in Orlando, Florida in 1998. The fundamental concepts of MOS were released to the public domain at that conference. [ 8 ]
As an open protocol , the MOS Development Group encourages the participation of broadcast equipment vendors and their customers. [ 9 ] More than 100 companies are said to work with AP on MOS-related projects. Compatible hardware and software includes video editing , storage and management ; automation ; machine control; prompters ; character generators; audio editing , store and management; web publishing , interactive TV , field transmission and graphics . [ 7 ]
Current development is happening on two tracks: a socket-based version, and a web service version. The current official versions of the MOS protocol, as of January 2011, are 2.8.4 (sockets) and 3.8.4 (web service). [ 10 ]
In 2016 proposals began to introduce IP Video support in the MOS protocol. This proposal allows representations of live IP Video sources such as NDI ( Network Device Interface ) to be included as MOS objects alongside MOS objects representing files to be played off disk [ 11 ]
There is also a Java based implementation called jmos that is currently compatible with MOS specification 2.8.2. [ 12 ]
An open source TypeScript (dialect of JavaScript ) MOS connector [ 13 ] and MOS Gateway [ 14 ] is being actively developed by the Norwegian state broadcaster NRK , as part of their open-source Sofie [ 15 ] broadcast automation software initiative.
An open source Python library and command line tool called mosromgr was developed by the BBC . [ 16 ] The mosromgr library provides functionality for classifying MOS file types, processing and inspecting MOS message files, as well as merging a batch of MOS files into a complete running order. [ 17 ]
In 2017 the National Academy of Television Arts and Sciences awarded an Emmy to the MOS Group for "Development and Standardization of Media Object Server (MOS) Protocol." [ 18 ] | https://en.wikipedia.org/wiki/Media_Object_Server |
Media Redundancy Protocol ( MRP ) is a data network protocol standardized by the International Electrotechnical Commission as IEC 62439-2. It allows rings of Ethernet switches to overcome any single failure with recovery time much faster than achievable with Spanning Tree Protocol . [ 1 ] It is suitable to most industrial Ethernet applications.
MRP operates at the data link layer (OSI Layer 2) of Ethernet switches and is a direct evolution of the HiPER-Ring protocol developed by Hirschmann in 1998. [ 2 ] [ 3 ] Hirschmann is now owned by Belden . [ 4 ] MRP is supported by several commercial industrial Ethernet switches. [ 5 ] [ 6 ]
In an MRP ring, the ring manager is named Media Redundancy Manager (MRM), while ring clients are named Media Redundancy Clients (MRCs).
MRM and MRC ring ports support three statuses: disabled, blocked, and forwarding:
During normal operation, the network works in the Ring-Closed status (Figure 1). In this status, one of the MRM ring ports is blocked, while the other is forwarding. Conversely, both ring ports of all MRCs are forwarding. Loops are avoided because the physical ring topology is reduced to a logical line topology.
In case of failure, the network works in the Ring-Open status (Figure 2). For instance, in case of failure of a link connecting two MRCs, the MRM sets both of its ring ports to the forwarding state; the MRCs adjacent to the failure each have a disabled port (because of the link loss) and a forwarding ring port; the other MRCs have both ring ports forwarding. Also, in the Ring-Open status, the network logical topology is a line.
MRP information is sent in the form of an Ethernet frame , with the EtherType field set to 0x88E3. The frames are built by Type–length–value (TLV) structures, allowing organizationally specific information.
The International Electrotechnical Commission standard for MRP was published in 2010 as IEC 62439-2 [ 7 ] and amended in 2012. [ citation needed ]
The standard IEC 62439 published in 2012 also defined the following protocols:
With the settings specified in IEC 62439-2, MRP guarantees a worst-case recovery time of 500 ms, 200 ms, or 30 ms in rings composed of up to 50 switches, and a worst-case recovery time of 10 ms in rings composed of up to 14 switches. | https://en.wikipedia.org/wiki/Media_Redundancy_Protocol |
In digital electronics , analogue electronics and entertainment , the user interface may include media controls , transport controls or player controls , to enact and change or adjust the process of video playback, audio playback, and alike. These controls are commonly depicted as widely known symbols found in a multitude of products, exemplifying what is known as dominant design .
Media control symbols are commonly found on both software and physical media players, remote controls , and multimedia keyboards . Their application is described in ISO/IEC 18035. [ 1 ]
The main symbols date back to the 1960s, with the Pause symbol having reportedly been invented at Ampex during that decade for use on reel-to-reel audio recorder controls, due to the difficulty of translating the word "pause" into some languages used in foreign markets. The Pause symbol was designed as a combination of the existing square Stop symbol and the caesura , and was intended to evoke the concept of an interruption or "stutter stop". [ 2 ] [ 3 ] The right-pointing triangle was adopted to indicate the direction of tape movement during playback. This design choice was straightforward: the arrow pointed in the direction the tape advanced. Over time, this symbol became standardized across various media devices, from cassette players to CD players, and eventually digital interfaces. [ 4 ]
To identify a feature or a selector control that reverses automatically the tape running direction every time the tape comes to either of its limits.
The Play symbol is arguably the most widely used of the media control symbols. In many ways, this symbol has become synonymous with music culture and more broadly the digital download era. As such, there are now a multitude of items such as T-shirts, posters, and tattoos that feature this symbol. [ citation needed ] Similar cultural references can be observed with the Power symbol which is especially popular among video gamers and technology enthusiasts.
Media symbols can be found on an array of advertisements: from live music venues to streaming services.
In 2012, Google rebranded its digital download store to Google Play , [ 8 ] using the Play symbol in its logo. The Play symbol also serves as a logo for YouTube since 2017. [ 9 ] Television station owners Morgan Murphy Media and TEGNA have begun to institute the Play symbol into the logos of their stations to further connect their websites to their over-the-air television presences.
In recent years, [ when? ] there has been a proliferation of electronics that use media control symbols in order to represent the Run, Stop, and Pause functions. Likewise, user interface programing pertaining to these functions has also been influenced by that of media players. [ citation needed ]
For example, some washers and dryers with an illuminated Play/pause button are programmed such that it stays lit when the appliance is running. A line of Philips pasta makers has the Play/pause button for controlling the pasta-making process. [ 10 ] | https://en.wikipedia.org/wiki/Media_control_symbols |
A media filter is a type of filter that uses a bed of sand , peat , shredded tires, foam, crushed glass, geo-textile fabric, anthracite , crushed granite or other material to filter water for drinking, swimming pools , aquaculture , irrigation , stormwater management, oil and gas operations, and other applications.
Each layer of media is designed to filter out specific types and sizes of particles, allowing for more efficient and effective removal of contaminants.
One design brings the water in the top of a container through a "header" which distributes the water evenly. The filter "media" start with fine sand on the top and then becomes gradually coarser sand in a number of layers followed by gravel on the bottom, in gradually larger sizes. The top sand physically removes particles from the water. The job of the subsequent layers is to support the finer layer above and provide efficient drainage.
As particles become trapped in the media, the differential pressure across the bed increases. Periodically, a backwash may be initiated to remove the solids trapped in the bed. During backwash, flow is directed in the opposite direction from normal flow. In multi-media filters, the layers in the media re-stratify due to density differences prior to resuming normal filtration. Multimedia filter can remove particles down to 10-25 microns.
Media filters are used in drinking water treatment, where multimedia filters are used as a primary or secondary filtration step to remove a wider range of particle sizes and types than sand filters, including organic matter and smaller particles.
Municipal drinking water systems often use a rapid sand filter and/or a slow sand filter for purification . Silica sand is the most widely used medium in such filters. [ 1 ] Anthracite coal, garnet sand, ilmenite, granular activated carbon, manganese green sand and crushed recycled glass are among the alternative filter media used. [ 2 ]
Media filters are used to protect water quality in streams , rivers , and lakes . They can be effective at removing pollutants in stormwater such as suspended solids and phosphorus . Sand is the most common filter material. [ 3 ] [ 4 ] In other filters, sometimes called "organic filters," wood chips or leaf mold may be used. [ 5 ]
Media filters are also used for cleaning the effluent from septic tanks and primary settlement tanks. The materials commonly used are sand, peat and natural stone fibre.
The oil and gas industry uses media filters for various purposes in both upstream and downstream operations. Nut shell filters are commonly used as a tertiary oil removal step for treatment of produced water . Sand filters are often used to remove fine solids following biological treatment and clarification of oil refinery wastewater. Multi-media filters are used for removing suspended solids from both produced water and refinery wastewater. The materials commonly used in multi-media filters are gravel, sand, garnet, and anthracite. [ citation needed ]
References
Nalco Water, an Ecolab Company. Nalco Water Handbook, Fourth Edition (McGraw-Hill Education: New York, Chicago, San Francisco, Athens, London, Madrid, Mexico City, Milan, New Delhi, Singapore, Sydney, Toronto, 2018). https://www.accessengineeringlibrary.com/content/book/9781259860973 | https://en.wikipedia.org/wiki/Media_filter |
Media player software is a type of application software for playing multimedia computer files like audio and video files. Media players commonly display standard media control icons known from physical devices such as tape recorders and CD players , such as play ( ), pause ( ), fastforward (⏩️), rewind (⏪), and stop ( ) buttons. In addition, they generally have progress bars (or "playback bars"), which are sliders to locate the current position in the duration of the media file.
Mainstream operating systems have at least one default media player. For example, Windows comes with Windows Media Player , Microsoft Movies & TV and Groove Music , while macOS comes with QuickTime Player and Music . Linux distributions come with different media players, such as SMPlayer , Amarok , Audacious , Banshee , MPlayer , mpv , Rhythmbox , Totem , VLC media player , and xine . Android comes with YouTube Music for audio and Google Photos for video, and smartphone vendors such as Samsung may bundle custom software.
The basic feature set of media players are a seek bar, a timer with the current and total playback time, playback controls (play, pause, previous, next, stop), playlists, a "repeat" mode, and a "shuffle" (or "random") mode for curiosity and to facilitate searching long timelines of files.
Different media players have different goals and feature sets. Video players are a group of media players that have their features geared more towards playing digital video . For example, Windows DVD Player exclusively plays DVD-Video discs and nothing else. Media Player Classic can play individual audio and video files but many of its features such as color correction, picture sharpening, zooming, set of hotkeys , DVB support and subtitle support are only useful for video material such as films and cartoons. Audio players , on the other hand, specialize in digital audio . For example, AIMP exclusively plays audio formats. MediaMonkey can play both audio and video formats, but many of its features including media library, lyric discovery, music visualization , online radio, audiobook indexing, and tag editing are geared toward consumption of audio material; watching video files on it can be a trying feat. General-purpose media players also do exist. For example, Windows Media Player has exclusive features for both audio and video material, although it cannot match the feature set of Media Player Classic and MediaMonkey combined.
By default, videos are played with fully visible field of view while filling at least either width or height of the viewport to appear as large as possible. Options to change the video's scaling and aspect ratio may include filling the viewport through either stretching or cropping, and "100% view" where each pixel of the video covers exactly one pixel on the screen. [ 1 ]
Zooming into the field of view during playback may be implemented through a slider on any screen or with pinch zoom on touch screens, and moving the field of view may be implemented through scrolling by dragging inside the view port or by moving a rectangle inside a miniature view of the entire field of view that denotes the magnified area. [ 2 ] [ 3 ]
Media player software may have the ability to adjust appearance and acoustics during playback using effects such as mirroring, rotating, cropping, cloning, adjusting colours, deinterlacing , and equalizing and visualizing audio . Easter eggs may be featured, such as a puzzle game on VLC Media Player . [ 4 ] [ 5 ]
Still snapshots may be extracted directly from a video frame or captured through a screenshot, the former of which is preferred since it preserves videos' original dimensions (height and width). [ 6 ] Video players may show a tooltip bubble previewing footage at the position hovered over with the mouse cursor. [ 7 ]
A preview tooltip for the seek bar has been implemented on few smartphones through a stylus or a self-capacitive touch screen able to detect a floating finger. Such include the Samsung Galaxy S4, S5 (finger), Note 2, Note 4 (stylus), and Note 3 (both).
Streaming media players may indicate buffered segments of the media in the seek bar. [ 8 ]
3D video players are used to play 2D video in 3D format. A high-quality three-dimensional video presentation requires that each frame of a motion picture be embedded with information on the depth of objects present in the scene. This process involves shooting the video with special equipment from two distinct perspectives or modeling and rendering each frame as a collection of objects composed of 3D vertices and textures, much like in any modern video game, to achieve special effects. Tedious and costly, this method is only used in a small fraction of movies produced worldwide, while most movies remain in the form of traditional 2D images. It is, however, possible to give an otherwise two-dimensional picture the appearance of depth. Using a technique known as anaglyph processing a "flat" picture can be transformed so as to give an illusion of depth when viewed through anaglyph glasses (usually red-cyan). An image viewed through anaglyph glasses appears to have both protruding and deeply embedded objects in it, at the expense of somewhat distorted colors. The method itself is old enough , dating back to the mid-19th century, but it is only with recent advances in computer technology that it has become possible to apply this kind of transformation to a series of frames in a motion picture reasonably fast or even in real-time, i.e. as the video is being played back. Several implementations exist in the form of 3D video players that render conventional 2D video in anaglyph 3D, as well as in the form of 3D video converters that transform video into stereoscopic anaglyph and transcode it for playback with regular software or hardware video players. [ citation needed ]
Well known examples of media player software include Windows Media Player , VLC media player , iTunes , Winamp , Media Player Classic , MediaMonkey , foobar2000 , AIMP , MusicBee and JRiver Media Center . Most of these also include music library managers.
Although media players are often multi-media, they can be primarily designed for a specific media. For example, Media Player Classic and VLC media player are video-focused while Winamp and iTunes are music-focused, despite all of them supporting both types of media.
A home theater PC or media center computer is a convergence device that combines some or all the capabilities of a personal computer with a software application that supports video, photo, audio playback, and sometimes video recording functionality. Although computers with some of these capabilities were available from the late 1980s, the "Home Theater PC" term first appeared in mainstream press in 1996. Since 2007, other types of consumer electronics, including gaming systems and dedicated media devices have crossed over to manage video and music content. The term "media center" also refers to specialized computer programs designed to run on standard personal computers . [ 9 ] | https://en.wikipedia.org/wiki/Media_player_software |
A media server is a computer appliance or an application software that stores digital media (video, audio or images) and makes it available over a network.
Media servers range from servers that provide video on demand to smaller personal computers or NAS (Network Attached Storage) for the home.
By definition, a media server is a device that simply stores and shares media. This definition is vague, and can allow several different devices to be called media servers. It may be a NAS drive, a home theater PC running Windows XP Media Center Edition , MediaPortal or MythTV , or a commercial web server that hosts media for a large web site. In a home setting, a media server acts as an aggregator of information: video , audio , photos, books, etc. These different types of media (whether they originated on DVD , CD , digital camera , or in physical form) are stored on the media server's hard drive . Access to these is then available from a central location. It may also be used to run special applications that allow the user(s) to access the media from a remote location via the internet.
The only requirement for a media server is a method of storing media and a network connection with enough bandwidth to allow access to that media. Depending on the uses and applications that it runs, a media server may require large amounts of RAM , or a powerful multicore CPU . A RAID array may be used to create a large amount of storage, though it is generally not necessary in a home media server to use a RAID array that gives a performance increase because current home network transfer speeds are slower than that of most current hard drives . However, a RAID configuration may be used to prevent loss of the media files due to disk failure as well.
Many media servers also have the ability to capture media. This is done with specialized hardware such as TV tuner cards. Analog TV tuner cards can capture video from analog broadcast TV and output from cable/satellite set top boxes. This analog video then needs to be encoded in digital format to be stored on the media server. This encoding can be done with software running on the Media server computer or by hardware on the TV tuner card. Digital TV tuner cards take input from broadcast digital TV. In North America and in South Korea, the ATSC standard is used. In most of the rest of the world, DVB-T is the accepted standard. Since these transmissions are already digital, they do not need to be encoded.
A variety of packages are available to run a home theater or media center.
The growing use of motion graphics in environments such as theatre , dance , corporate events and concerts has led to the development of media servers designed specifically for live events. These machines are often high-spec PC computers with high-speed hard drive technologies such as RAID arrays or solid-state drives , multiple GPUs and optionally a video capture board to allow mixing live video with recorded content and real-time effects. The supplied software is usually a suite of tools starting with the main VJ environment where the user defines a number of set layers, each switchable between live, stored media or real-time generated, and layering modes between them. All of these introduce parameters of which manipulation of values in these parameters over time become the performance. High-end media server systems include support for DMX512-A , MIDI , Art-Net or similar control protocols to allow multiple remote sources like sliders, buttons and knobs on a control console to drive these parameters, as well as sending commands from the media server to for instance control RGB or moving lighting and other stage effects.
A major feature of high-end media servers is projection mapping, where multiple video projectors can project images onto irregularly shaped and positioned set pieces and even track their motion. This is usually done beforehand by the designer mapping their full set out in 3D in a pre-visualization tool.
In the world of telephony, a media server is the computing component that processes the audio or video streams associated with telephone calls or connections. Conference services are a particular example of how media servers can be used, as a special 'engine' is needed to mix audio streams together so that conference participants can hear all of the other participants. Conferencing servers may also need other specialized functions like "loudest talker" detection, or transcoding of audio streams, and also interpreting DTMF tones used to navigate menus. For video processing, it may be needed to change video streams, for example transcode from one video codec to another or rescale a picture from one size to another. These media processing functions are the core responsibility of a media server.
With telephony networks moving towards VoIP technology, and using Session Initiation Protocol (SIP), the idea of media servers has started to gain some traction. Typically, an application (the 'application server') has the controlling logic, and controls a remote media server (or multiple servers) over an IP connection, possibly using SIP. Protocols such as Netann, MSCML and MSML have been created for this way of working, and a new protocol, MediaCTRL, is under development at the IETF .
The IP Multimedia Subsystem (IMS), the blueprint for next generation networks, defines a component called the MRF (Media Resource Function), which is a kind of media server. In the case of IMS, the 'controlling logic' is provided by the MRFC (MRF controller), which, along with layers above, constitutes an 'application server'. Although the MRF has been associated largely with the legacy telecom H.248 protocol (see Gateway Control Protocol ), it is claimed that SIP-based protocols like MediaCTRL will ultimately prevail.
Media servers in cinema allow users to download and watch high quality content by utilizing a movie player and plugging into a display or AV system. Kaleidescape offers a movie server to store and cache content that enhances player performance. [ 1 ] [ 2 ] | https://en.wikipedia.org/wiki/Media_server |
In geometry , a median of a triangle is a line segment joining a vertex to the midpoint of the opposite side, thus bisecting that side. Every triangle has exactly three medians, one from each vertex, and they all intersect at the triangle's centroid . In the case of isosceles and equilateral triangles, a median bisects any angle at a vertex whose two adjacent sides are equal in length.
The concept of a median extends to tetrahedra .
Each median of a triangle passes through the triangle's centroid , which is the center of mass of an infinitely thin object of uniform density coinciding with the triangle. [ 1 ] Thus, the object would balance at the intersection point of the medians. The centroid is twice as close along any median to the side that the median intersects as it is to the vertex it emanates from.
Each median divides the area of the triangle in half, hence the name, and hence a triangular object of uniform density would balance on any median. (Any other lines that divide triangle's area into two equal parts do not pass through the centroid.) [ 2 ] [ 3 ] The three medians divide the triangle into six smaller triangles of equal area .
Consider a triangle ABC . Let D be the midpoint of A B ¯ {\displaystyle {\overline {AB}}} , E be the midpoint of B C ¯ {\displaystyle {\overline {BC}}} , F be the midpoint of A C ¯ {\displaystyle {\overline {AC}}} , and O be the centroid (most commonly denoted G ).
By definition, A D = D B , A F = F C , B E = E C {\displaystyle AD=DB,AF=FC,BE=EC} . Thus [ A D O ] = [ B D O ] , [ A F O ] = [ C F O ] , [ B E O ] = [ C E O ] , {\displaystyle [ADO]=[BDO],[AFO]=[CFO],[BEO]=[CEO],} and [ A B E ] = [ A C E ] {\displaystyle [ABE]=[ACE]} , where [ A B C ] {\displaystyle [ABC]} represents the area of triangle △ A B C {\displaystyle \triangle ABC} ; these hold because in each case the two triangles have bases of equal length and share a common altitude from the (extended) base, and a triangle's area equals one-half its base times its height.
We have:
Thus, [ A B O ] = [ A C O ] {\displaystyle [ABO]=[ACO]} and [ A D O ] = [ D B O ] , [ A D O ] = 1 2 [ A B O ] {\displaystyle [ADO]=[DBO],[ADO]={\frac {1}{2}}[ABO]}
Since [ A F O ] = [ F C O ] , [ A F O ] = 1 2 [ A C O ] = 1 2 [ A B O ] = [ A D O ] {\displaystyle [AFO]=[FCO],[AFO]={\frac {1}{2}}[ACO]={\frac {1}{2}}[ABO]=[ADO]} , therefore, [ A F O ] = [ F C O ] = [ D B O ] = [ A D O ] {\displaystyle [AFO]=[FCO]=[DBO]=[ADO]} .
Using the same method, one can show that [ A F O ] = [ F C O ] = [ D B O ] = [ A D O ] = [ B E O ] = [ C E O ] {\displaystyle [AFO]=[FCO]=[DBO]=[ADO]=[BEO]=[CEO]} .
In 2014 Lee Sallows discovered the following theorem: [ 4 ]
The lengths of the medians can be obtained from Apollonius' theorem as: m a = 1 2 2 b 2 + 2 c 2 − a 2 {\displaystyle m_{a}={\frac {1}{2}}{\sqrt {2b^{2}+2c^{2}-a^{2}}}} m b = 1 2 2 a 2 + 2 c 2 − b 2 {\displaystyle m_{b}={\frac {1}{2}}{\sqrt {2a^{2}+2c^{2}-b^{2}}}} m c = 1 2 2 a 2 + 2 b 2 − c 2 {\displaystyle m_{c}={\frac {1}{2}}{\sqrt {2a^{2}+2b^{2}-c^{2}}}} where a , b , {\displaystyle a,b,} and c {\displaystyle c} are the sides of the triangle with respective medians m a , m b , {\displaystyle m_{a},m_{b},} and m c {\displaystyle m_{c}} from their midpoints.
These formulas imply the relationships: [ 5 ] a = 2 3 − m a 2 + 2 m b 2 + 2 m c 2 = 2 ( b 2 + c 2 ) − 4 m a 2 = b 2 2 − c 2 + 2 m b 2 = c 2 2 − b 2 + 2 m c 2 {\displaystyle a={\frac {2}{3}}{\sqrt {-m_{a}^{2}+2m_{b}^{2}+2m_{c}^{2}}}={\sqrt {2(b^{2}+c^{2})-4m_{a}^{2}}}={\sqrt {{\frac {b^{2}}{2}}-c^{2}+2m_{b}^{2}}}={\sqrt {{\frac {c^{2}}{2}}-b^{2}+2m_{c}^{2}}}} b = 2 3 − m b 2 + 2 m a 2 + 2 m c 2 = 2 ( a 2 + c 2 ) − 4 m b 2 = a 2 2 − c 2 + 2 m a 2 = c 2 2 − a 2 + 2 m c 2 {\displaystyle b={\frac {2}{3}}{\sqrt {-m_{b}^{2}+2m_{a}^{2}+2m_{c}^{2}}}={\sqrt {2(a^{2}+c^{2})-4m_{b}^{2}}}={\sqrt {{\frac {a^{2}}{2}}-c^{2}+2m_{a}^{2}}}={\sqrt {{\frac {c^{2}}{2}}-a^{2}+2m_{c}^{2}}}} c = 2 3 − m c 2 + 2 m b 2 + 2 m a 2 = 2 ( b 2 + a 2 ) − 4 m c 2 = b 2 2 − a 2 + 2 m b 2 = a 2 2 − b 2 + 2 m a 2 . {\displaystyle c={\frac {2}{3}}{\sqrt {-m_{c}^{2}+2m_{b}^{2}+2m_{a}^{2}}}={\sqrt {2(b^{2}+a^{2})-4m_{c}^{2}}}={\sqrt {{\frac {b^{2}}{2}}-a^{2}+2m_{b}^{2}}}={\sqrt {{\frac {a^{2}}{2}}-b^{2}+2m_{a}^{2}}}.}
Let ABC be a triangle, let G be its centroid, and let D , E , and F be the midpoints of BC , CA , and AB , respectively. For any point P in the plane of ABC then [ 6 ] P A + P B + P C ≤ 2 ( P D + P E + P F ) + 3 P G . {\displaystyle PA+PB+PC\leq 2(PD+PE+PF)+3PG.}
The centroid divides each median into parts in the ratio 2:1, with the centroid being twice as close to the midpoint of a side as it is to the opposite vertex.
For any triangle with sides a , b , c {\displaystyle a,b,c} and medians m a , m b , m c , {\displaystyle m_{a},m_{b},m_{c},} [ 7 ] 3 4 ( a + b + c ) < m a + m b + m c < a + b + c and 3 4 ( a 2 + b 2 + c 2 ) = m a 2 + m b 2 + m c 2 . {\displaystyle {\tfrac {3}{4}}(a+b+c)<m_{a}+m_{b}+m_{c}<a+b+c\quad {\text{ and }}\quad {\tfrac {3}{4}}\left(a^{2}+b^{2}+c^{2}\right)=m_{a}^{2}+m_{b}^{2}+m_{c}^{2}.}
The medians from sides of lengths a {\displaystyle a} and b {\displaystyle b} are perpendicular if and only if a 2 + b 2 = 5 c 2 . {\displaystyle a^{2}+b^{2}=5c^{2}.} [ 8 ]
The medians of a right triangle with hypotenuse c {\displaystyle c} satisfy m a 2 + m b 2 = 5 m c 2 . {\displaystyle m_{a}^{2}+m_{b}^{2}=5m_{c}^{2}.}
Any triangle's area T can be expressed in terms of its medians m a , m b {\displaystyle m_{a},m_{b}} , and m c {\displaystyle m_{c}} as follows. If their semi-sum ( m a + m b + m c ) / 2 {\displaystyle \left(m_{a}+m_{b}+m_{c}\right)/2} is denoted by σ {\displaystyle \sigma } then [ 9 ] T = 4 3 σ ( σ − m a ) ( σ − m b ) ( σ − m c ) . {\displaystyle T={\frac {4}{3}}{\sqrt {\sigma \left(\sigma -m_{a}\right)\left(\sigma -m_{b}\right)\left(\sigma -m_{c}\right)}}.}
A tetrahedron is a three-dimensional object having four triangular faces . A line segment joining a vertex of a tetrahedron with the centroid of the opposite face is called a median of the tetrahedron. There are four medians, and they are all concurrent at the centroid of the tetrahedron. [ 10 ] As in the two-dimensional case, the centroid of the tetrahedron is the center of mass . However contrary to the two-dimensional case the centroid divides the medians not in a 2:1 ratio but in a 3:1 ratio ( Commandino's theorem ). | https://en.wikipedia.org/wiki/Median_(geometry) |
The Median Wall was a wall built to the north of the ancient city of Babylon at a point where the distance between the rivers Tigris and Euphrates decreases considerably. It was believed to have been constructed during the latter part of the reign of Nebuchadrezzar II and to have consisted of baked brick and bitumen , [ 1 ] with centre of the wall being packed with earth. The wall was built to prevent any potential invasion by the Medes from the north — hence the name 'Median' Wall.
The ancient Greek writer Xenophon states that the wall was in existence in 401 BC in his book the Anabasis (or 'The Persian Expedition'), and described it as being 20 feet (6.1 m) wide and 100 feet (30 m) in height, and 20 parasangs in length (approximately 70 miles or 110 kilometres). [ 1 ]
This Iraq geographical location article is a stub . You can help Wikipedia by expanding it . | https://en.wikipedia.org/wiki/Median_Wall |
Median aerodynamic diameter ( MAD ) is one of two parameters influencing the deposition of inhaled particles, the other being the geometric standard deviation of the particle size distribution. The MAD is the value of aerodynamic diameter for which 50% of some quantity in a given aerosol is associated with particles smaller than the MAD, and 50% of the quantity is associated with particles larger than the MAD. It simplifies the true distribution of aerodynamic diameters of a given aerosol as a single value. It is also used to describe those particle sizes for which deposition depends chiefly on inertial impaction and sedimentation. [ 1 ]
In the context of radiation protection , activity median aerodynamic diameter ( AMAD ) is the MAD for the airborne activity in a given aerosol . Internal dosimetry uses it as a means of simplifying the true distribution of aerodynamic diameters of a given aerosol. [ 1 ]
Count median aerodynamic diameter ( CMAD ) [ 2 ] is only used rarely. Half of the particles (by count) of a given aerosol have the aerodynamic diameter smaller than the CMAD, and the other half larger. A similar quantity, count median (geometric) diameter (CMD) is more common.
Mass median aerodynamic diameter ( MMAD ) is the MAD for mass.
This nuclear technology article is a stub . You can help Wikipedia by expanding it .
This radioactivity –related article is a stub . You can help Wikipedia by expanding it . | https://en.wikipedia.org/wiki/Median_aerodynamic_diameter |
In toxicology , the median lethal dose , LD 50 (abbreviation for " lethal dose , 50%"), LC 50 (lethal concentration, 50%) or LCt 50 is a toxic unit that measures the lethal dose of a given substance . [ 1 ] The value of LD 50 for a substance is the dose required to kill half the members of a tested population after a specified test duration. LD 50 figures are frequently used as a general indicator of a substance's acute toxicity . A lower LD 50 is indicative of higher toxicity.
The term LD 50 is generally attributed to John William Trevan. [ 2 ] The test was created by J. W. Trevan in 1927. [ 3 ] The term semilethal dose is occasionally used in the same sense, in particular with translations of foreign language text, but can also refer to a sublethal dose. LD 50 is usually determined by tests on animals such as laboratory mice . In 2011, the U.S. Food and Drug Administration approved alternative methods to LD 50 for testing the cosmetic drug botox without animal tests. [ 4 ] [ 5 ]
The LD 50 is usually expressed as the mass of substance administered per unit mass of test subject, typically as milligrams of substance per kilogram of body mass, sometimes also stated as nanograms (suitable for botulinum toxin ), micrograms , or grams (suitable for paracetamol ) per kilogram. Stating it this way allows the relative toxicity of different substances to be compared and normalizes for the variation in the size of the animals exposed (although toxicity does not always scale simply with body mass). For substances in the environment, such as poisonous vapors or substances in water that are toxic to fish, the concentration in the environment (per cubic metre or per litre) is used, giving a value of LC 50 . But in this case, the exposure time is important (see below).
The choice of 50% lethality as a benchmark avoids the potential for ambiguity of making measurements in the extremes and reduces the amount of testing required. However, this also means that LD 50 is not the lethal dose for all subjects; some may be killed by much less, while others survive doses far higher than the LD 50 . Measures such as "LD 1 " and "LD 99 " (dosage required to kill 1% or 99%, respectively, of the test population) are occasionally used for specific purposes. [ 6 ]
Lethal dosage often varies depending on the method of administration ; for instance, many substances are less toxic when administered orally than when intravenously administered. For this reason, LD 50 figures are often qualified with the mode of administration, e.g., "LD 50 i.v."
The related quantities LD 50 /30 or LD 50 /60 are used to refer to a dose that without treatment will be lethal to 50% of the population within (respectively) 30 or 60 days. These measures are used more commonly within radiation health physics , for ionizing radiation , as survival beyond 60 days usually results in recovery.
A comparable measurement is LCt 50 , which relates to lethal dosage from exposure, where C is concentration and t is time. It is often expressed in terms of mg-min/m 3 . ICt 50 is the dose that will cause incapacitation rather than death. These measures are commonly used to indicate the comparative efficacy of chemical warfare agents, and dosages are typically qualified by rates of breathing (e.g., resting = 10 L/min) for inhalation, or degree of clothing for skin penetration. The concept of Ct was first proposed by Fritz Haber and is sometimes referred to as Haber's law , which assumes that exposure to 1 minute of 100 mg/m 3 is equivalent to 10 minutes of 10 mg/m 3 (1 × 100 = 100, as does 10 × 10 = 100).
Some chemicals, such as hydrogen cyanide , are rapidly detoxified by the human body, and do not follow Haber's law. In these cases, the lethal concentration may be given simply as LC 50 and qualified by a duration of exposure (e.g., 10 minutes). The material safety data sheets for toxic substances frequently use this form of the term even if the substance does follow Haber's law.
For disease-causing organisms, there is also a measure known as the median infective dose and dosage. The median infective dose (ID 50 ) is the number of organisms received by a person or test animal qualified by the route of administration (e.g., 1,200 org/man per oral). Because of the difficulties in counting actual organisms in a dose, infective doses may be expressed in terms of biological assay, such as the number of LD 50 s to some test animal. In biological warfare infective dosage is the number of infective doses per cubic metre of air times the number of minutes of exposure (e.g., ICt 50 is 100 medium doses - min/m 3 ).
As a measure of toxicity, LD 50 is somewhat unreliable and results may vary greatly between testing facilities due to factors such as the genetic characteristics of the sample population, animal species tested, environmental factors and mode of administration. [ 7 ]
There can be wide variability between species as well; what is relatively safe for rats may very well be extremely toxic for humans ( cf. paracetamol toxicity ), and vice versa. For example, chocolate, comparatively harmless to humans, is known to be toxic to many animals . When used to test venom from venomous creatures, such as snakes , LD 50 results may be misleading due to the physiological differences between mice, rats, and humans. Many venomous snakes are specialized predators on mice, and their venom may be adapted specifically to incapacitate mice; and mongooses may be exceptionally resistant. While most mammals have a very similar physiology, LD 50 results may or may not have equal bearing upon every mammal species, such as humans, etc.
Note: Comparing substances (especially drugs) to each other by LD 50 can be misleading in many cases due (in part) to differences in effective dose (ED 50 ). Therefore, it is more useful to compare such substances by therapeutic index , which is simply the ratio of LD 50 to ED 50 . [ 8 ]
The following examples are listed in reference to LD 50 values, in descending order, and accompanied by LC 50 values, {bracketed}, when appropriate.
human, smoking
The LD 50 values have a very wide range. The botulinum toxin as the most toxic substance known has an LD 50 value of 1 ng/kg, while the most non-toxic substance water has an LD 50 value of more than 90 g/kg; a difference of about 1 in 100 billion, or 11 orders of magnitude. As with all measured values that differ by many orders of magnitude, a logarithmic view is advisable. Well-known examples are the indication of the earthquake strength using the Richter scale , the pH value , as a measure for the acidic or basic character of an aqueous solution or of loudness in decibels .
In this case, the negative decimal logarithm of the LD 50 values, which is standardized in kg per kg body weight, is considered −log 10 (LD 50 ) .
The dimensionless value found can be entered in a toxin scale. Water as the baseline substance is nearly 1 in the negative logarithmic toxin scale.
A number of procedures have been defined to derive the LD 50 . The earliest was the 1927 "conventional" procedure by Trevan, which requires 40 or more animals. The fixed-dose procedure , proposed in 1984, estimates a level of toxicity by feeding at defined doses and looking for signs of toxicity (without requiring death). [ 108 ] The up-and-down procedure , proposed in 1985, yields an LD 50 value while dosing only one animal at a time. [ 109 ] [ 110 ] | https://en.wikipedia.org/wiki/Median_lethal_dose |
In toxicology , the median toxic dose ( TD 50 ) of a drug or toxin is the dose at which toxicity occurs in 50% of cases. [ 1 ] : 73 The type of toxicity should be specified for this value to have meaning for practical purposes. The median toxic dose encompasses the category of toxicity that is greater than half maximum effective concentration ( ED 50 ) but less than the median lethal dose (LD 50 ). However, for some highly potent toxins (ex. lofentanil , botulinum toxin ) the difference between the ED 50 and TD 50 is so minute that the values assigned to them may be approximated to equal doses. Since toxicity need not be lethal, the TD 50 is generally lower than the median lethal dose (LD 50 ), and the latter can be considered an upper bound for the former. However, since the toxicity is above the effective limit, the TD 50 is generally greater than the ED 50 . If the result of a study is a toxic effect that does not result in death, it is classified as this form of toxicity. [ 2 ] Toxic effects can be defined differently, sometimes considering the therapeutic effect of a substance to be toxic (such as with chemotherapeutics ) which can lead to confusion and contention regarding a substance's TD 50 . Examples of these toxic endpoints include cancer, blindness, anemia, and birth defects. [ 2 ]
This pharmacology -related article is a stub . You can help Wikipedia by expanding it .
This toxicology -related article is a stub . You can help Wikipedia by expanding it . | https://en.wikipedia.org/wiki/Median_toxic_dose |
Condorcet methods
Positional voting
Cardinal voting
Quota-remainder methods
Approval-based committees
Fractional social choice
Semi-proportional representation
By ballot type
Pathological response
Strategic voting
Paradoxes of majority rule
Positive results
In political science and social choice , the median voter theorem states that if voters and candidates are distributed along a one-dimensional spectrum and voters have single-peaked preferences , any voting method that is compatible with majority-rule will elect the candidate preferred by the median voter.
The theorem was first set out by Duncan Black in 1948. [ 1 ] He wrote that he saw a large gap in economic theory concerning how voting determines the outcome of decisions, including political decisions. Black's paper triggered research on how economics can explain voting systems.
A different argument due to Anthony Downs and Harold Hotelling is only loosely-related to Black's median voter theorem, but is often confused with it. This model argues that politicians in a representative democracy will converge to the viewpoint of the median voter, [ 2 ] because the median voter theorem implies that a candidate who wishes to win will adopt the positions of the median voter. [ 2 ] [ 3 ] [ 4 ] However, this argument only applies to systems satisfying the median voter property, and cannot be applied to systems like ranked choice voting (RCV) or plurality voting outside of limited conditions (see § Hotelling–Downs model ). [ 5 ] [ 6 ] [ 7 ]
Say there is an election where candidates and voters have opinions distributed along a one-dimensional political spectrum . Voters rank candidates by proximity, i.e. the closest candidate is their first preference, the second-closest is their second preference, and so on. Then, the median voter theorem says that the candidate closest to the median voter is a majority-preferred (or Condorcet ) candidate . In other words, this candidate preferred to any one of their opponents by a majority of voters. When there are only two candidates, a simple majority vote satisfies this condition, while for multi-candidate votes any majority-rule (Condorcet) method will satisfy it.
Proof sketch: Let the median voter be Marlene. The candidate who is closest to her will receive her first preference vote. Suppose that this candidate is Charles and that he lies to her left. Marlene and all voters to her left (by definition a majority of the electorate) will prefer Charles to all candidates to his right, and Marlene and all voters to her right (also a majority) will prefer Charles to all candidates to his left. ∎
We will say that a voting method has the "median voter property in one dimension" if it always elects the candidate closest to the median voter under a one-dimensional spatial model. We may summarize the median voter theorem as saying that all Condorcet methods possess the median voter property in one dimension.
It turns out that Condorcet methods are not unique in this: Coombs' method is not Condorcet-consistent but nonetheless satisfies the median voter property in one dimension. [ 10 ] Approval voting satisfies the same property under several models of strategic voting.
It is impossible to fully generalize the median voter theorem to spatial models in more than one dimension, as there is no longer a single unique "median" for all possible distributions of voters. However, it is still possible to demonstrate similar theorems under some limited conditions.
The table shows an example of an election given by the Marquis de Condorcet , who concluded it showed a problem with the Borda count . [ 11 ] : 90 The Condorcet winner on the left is A, who is preferred to B by 41:40 and to C by 60:21. The Borda winner is instead B. However, Donald Saari constructs an example in two dimensions where the Borda count (but not the Condorcet winner) correctly identifies the candidate closest to the center (as determined by the geometric median ). [ 12 ]
The diagram shows a possible configuration of the voters and candidates consistent with the ballots, with the voters positioned on the circumference of a unit circle. In this case, A's mean absolute deviation is 1.15, whereas B's is 1.09 (and C's is 1.70), making B the spatial winner.
Thus the election is ambiguous in that two different spatial representations imply two different optimal winners. This is the ambiguity we sought to avoid earlier by adopting a median metric for spatial models; but although the median metric achieves its aim in a single dimension, the property does not fully generalize to higher dimensions.
Despite this result, the median voter theorem can be applied to distributions that are rotationally symmetric, e.g. Gaussians , which have a single median that is the same in all directions. Whenever the distribution of voters has a unique median in all directions, and voters rank candidates in order of proximity, the median voter theorem applies: the candidate closest to the median will have a majority preference over all his or her rivals, and will be elected by any voting method satisfying the median voter property in one dimension. [ 13 ]
It follows that all median voter methods satisfy the same property in spaces of any dimension, for voter distributions with omnidirectional medians.
It is easy to construct voter distributions which do not have a median in all directions. The simplest example consists of a distribution limited to 3 points not lying in a straight line, such as 1, 2 and 3 in the second diagram. Each voter location coincides with the median under a certain set of one-dimensional projections. If A, B and C are the candidates, then '1' will vote A-B-C, '2' will vote B-C-A, and '3' will vote C-A-B, giving a Condorcet cycle. This is the subject of the McKelvey–Schofield theorem .
Proof . See the diagram, in which the grey disc represents the voter distribution as uniform over a circle and M is the median in all directions. Let A and B be two candidates, of whom A is the closer to the median. Then the voters who rank A above B are precisely the ones to the left (i.e. the 'A' side) of the solid red line; and since A is closer than B to M, the median is also to the left of this line.
Now, since M is a median in all directions, it coincides with the one-dimensional median in the particular case of the direction shown by the blue arrow, which is perpendicular to the solid red line. Thus if we draw a broken red line through M, perpendicular to the blue arrow, then we can say that half the voters lie to the left of this line. But since this line is itself to the left of the solid red line, it follows that more than half of the voters will rank A above B.
Whenever a unique omnidirectional median exists, it determines the result of Condorcet voting methods. At the same time the geometric median can arguably be identified as the ideal winner of a ranked preference election. It is therefore important to know the relationship between the two. In fact whenever a median in all directions exists (at least for the case of discrete distributions), it coincides with the geometric median.
Lemma . Whenever a discrete distribution has a median M in all directions, the data points not located at M must come in balanced pairs ( A , A ' ) on either side of M with the property that A – M – A ' is a straight line (ie. not like A 0 – M – A 2 in the diagram).
Proof . This result was proved algebraically by Charles Plott in 1967. [ 14 ] Here we give a simple geometric proof by contradiction in two dimensions.
Suppose, on the contrary, that there is a set of points A i which have M as median in all directions, but for which the points not coincident with M do not come in balanced pairs. Then we may remove from this set any points at M , and any balanced pairs about M , without M ceasing to be a median in any direction; so M remains an omnidirectional median.
If the number of remaining points is odd, then we can easily draw a line through M such that the majority of points lie on one side of it, contradicting the median property of M .
If the number is even, say 2 n , then we can label the points A 0 , A 1 ,... in clockwise order about M starting at any point (see the diagram). Let θ be the angle subtended by the arc from M – A 0 to M – A n . Then if θ < 180° as shown, we can draw a line similar to the broken red line through M which has the majority of data points on one side of it, again contradicting the median property of M ; whereas if θ > 180° the same applies with the majority of points on the other side. And if θ = 180°, then A 0 and A n form a balanced pair, contradicting another assumption.
Theorem . Whenever a discrete distribution has a median M in all directions, it coincides with its geometric median.
Proof . The sum of distances from any point P to a set of data points in balanced pairs ( A , A ' ) is the sum of the lengths A – P – A '. Each individual length of this form is minimized over P when the line is straight, as happens when P coincides with M . The sum of distances from P to any data points located at M is likewise minimized when P and M coincide. Thus the sum of distances from the data points to P is minimized when P coincides with M .
A related observation was discussed by Harold Hotelling as his 'principle of minimum differentiation', also known as ' Hotelling's law '. It states that if:
Then all politicians will converge to the median voter. As a special case, this law applies to the situation where there are exactly two candidates in the race, if it is impossible or implausible that any more candidates will join the race, because a simple majority vote between two alternatives satisfies the Condorcet criterion .
This theorem was first described by Hotelling in 1929. [ 3 ] In practice, none of these conditions hold for modern American elections, though they may have held in Hotelling's time (when nominees were often previously-unknown and chosen by closed party caucuses in ideologically diverse parties). Most importantly, politicians must win primary elections , which often include challengers or competitors, to be chosen as major-party nominees. As a result, politicians must compromise between appealing to the median voter in the primary and general electorates. Similar effects imply candidates do not converge to the median voter under electoral systems that do not satisfy the median voter theorem, including plurality voting , plurality-with-primaries , plurality-with-runoff , or ranked-choice runoff (RCV) . [ 6 ] [ 15 ]
The theorem is valuable for the light it sheds on the optimality (and the limits to the optimality) of certain voting systems.
Valerio Dotti points out broader areas of application:
The Median Voter Theorem proved extremely popular in the Political Economy literature. The main reason is that it can be adopted to derive testable implications about the relationship between some characteristics of the voting population and the policy outcome, abstracting from other features of the political process. [ 13 ]
He adds that...
The median voter result has been applied to an incredible variety of questions. Examples are the analysis of the relationship between income inequality and size of governmental intervention in redistributive policies (Meltzer and Richard, 1981), [ 16 ] the study of the determinants of immigration policies (Razin and Sadka, 1999), [ 17 ] of the extent of taxation on different types of income (Bassetto and Benhabib, 2006), [ 18 ] and many more.
In the United States Senate , each state is allocated two seats. Levitt (1996) examined the voting patterns of pairs of senators from the same state when one belonged to the Democratic Party and the other to the Republican Party. According to the Median Voter Theorem , the voting patterns of two senators representing the same state should be identical, regardless of party affiliation. However, reality differs. Moreover, Levitt found that the similarity in their voting patterns was only slightly higher than that of randomly paired senators. This finding suggests that senators' ideological leanings have a stronger influence on their decisions than voters' preferences, contradicting the prediction of the Median Voter Theorem. [ 19 ]
Pande (2003) studied political changes in India between 1960 and 1992 that increased political representation for marginalized groups. The data she collected showed that as a result of these changes, transfer payments to these populations increased even though the overall electorate (which had already included these groups) remained unchanged. This finding contradicts the Median Voter Theorem, as the model predicts that such a political shift should not alter the political equilibrium. [ 20 ]
Chattopadhyay and Duflo (2004) examined another political change in India, which mandated that women lead one-third of village councils. These councils are responsible for providing various public goods to rural communities. According to the Median Voter Theorem , this policy should not have affected the composition of public goods supplied by local governments, as a female candidate still needs to be elected by a majority vote. As long as the median voter's preferences remain unchanged, the allocation of public goods should remain stable. However, empirical data showed that in villages where a woman was elected, the distribution of public goods shifted toward those preferred by women. Furthermore, in districts where women were elected for a second term, the allocation of public goods continued to reflect women's preferences. It is important to note, however, that while the composition of public goods changed when a woman led the village council, this does not necessarily imply an improvement or decline in overall social welfare. [ 21 ]
Similar findings were reported by Miller (2008), who analyzed the impact of granting women the right to vote across the United States in 1920. Miller built on previous research indicating that women prioritize child welfare more than men and demonstrated that extending voting rights to women led to an immediate shift in federal policy. This change resulted in a significant increase in healthcare spending and a consequent reduction in child mortality rates by 8%–15%. However, unlike previous cases, Miller's findings actually support the Median Voter Theorem. This is because granting women suffrage altered the composition of the electorate, shifting the median voter’s position toward the preferences of the new female voters. [ 22 ]
Lee, Moretti, and Butler (2004) investigated whether voters influence politicians' positions or merely choose from existing policy stances. They found that an exogenous shift in the voter base does not alter candidates' positions. For instance, an increase in Democratic voters in a given area does not push a Republican candidate’s stance further to the left, and vice versa. This finding suggests that the electorate selects from the positions that politicians already hold, rather than shaping those positions, contradicting the prediction of the Median Voter Theorem, which assumes candidates are ideologically neutral. [ 23 ]
Gerber and Lewis (2015) analyzed voting data from a series of referendums in California to estimate the preferences of the median voter. They found that elected officials are constrained by the preferences of the median voter in homogeneous regions but less so in heterogeneous ones. [ 24 ]
In contrast, Brunner and Ross (2010), who also studied voter data from two referendums in California, found that the decisive voter in votes concerning public expenditure was not the median voter, but rather a voter from the fourth income decile . This finding aligns with other studies suggesting that low-income voters often form coalitions with high-income voters to oppose increases in public spending. [ 25 ]
Referendum data from Switzerland was used by Stadelmann, Portmann, and Eichenberger (2012) to examine the degree to which legislators' votes align with the preferences of the median voter in their districts. Their research showed that the Median Voter Model explains legislative voting behavior better than an alternative random voting hypothesis, but only by a modest margin of 17.6%. Additionally, they found that support from the median voter in a senator’s district increases the likelihood of the senator supporting a given proposal by 8.4% in parliament. [ 26 ]
Milanovic (2000), using data from 79 countries, concluded that the greater the inequality in a country's pre-tax income distribution, the more aggressive the redistributive policies of the winning government. This finding supports the Median Voter Theorem . [ 27 ] | https://en.wikipedia.org/wiki/Median_voter_theorem |
In mathematics , the mediant of two fractions , generally made up of four positive integers
That is to say, the numerator and denominator of the mediant are the sums of the numerators and denominators of the given fractions, respectively. It is sometimes called the freshman sum , as it is a common mistake in the early stages of learning about addition of fractions .
Technically, this is a binary operation on valid fractions (nonzero denominator), considered as ordered pairs of appropriate integers, a priori disregarding the perspective on rational numbers as equivalence classes of fractions. For example, the mediant of the fractions 1/1 and 1/2 is 2/3. However, if the fraction 1/1 is replaced by the fraction 2/2, which is an equivalent fraction denoting the same rational number 1, the mediant of the fractions 2/2 and 1/2 is 3/4. For a stronger connection to rational numbers the fractions may be required to be reduced to lowest terms , thereby selecting unique representatives from the respective equivalence classes.
In fact, mediants commonly occur in the study of continued fractions and in particular, Farey fractions . The n th Farey sequence F n is defined as the (ordered with respect to magnitude) sequence of reduced fractions a / b (with coprime a , b ) such that b ≤ n . If two fractions a / c < b / d are adjacent (neighbouring) fractions in a segment of F n then the determinant relation b c − a d = 1 {\displaystyle bc-ad=1} mentioned above is generally valid and therefore the mediant is the simplest fraction in the interval ( a / c , b / d ), in the sense of being the fraction with the smallest denominator. Thus the mediant will then (first) appear in the ( c + d )th Farey sequence and is the "next" fraction which is inserted in any Farey sequence between a / c and b / d . This gives the rule how the Farey sequences F n are successively built up with increasing n .
The Stern–Brocot tree provides an enumeration of all positive rational numbers via mediants in lowest terms, obtained purely by iterative computation of the mediant according to a simple algorithm.
A positive rational number is one in the form a / b {\displaystyle a/b} where a , b {\displaystyle a,b} are positive natural numbers ; i.e. a , b ∈ N + {\displaystyle a,b\in \mathbb {N} ^{+}} . The set of positive rational numbers Q + {\displaystyle \mathbb {Q} ^{+}} is, therefore, the Cartesian product of N + {\displaystyle \mathbb {N} ^{+}} by itself; i.e. Q + = ( N + ) 2 {\displaystyle \mathbb {Q} ^{+}=(\mathbb {N} ^{+})^{2}} . A point with coordinates ( b , a ) {\displaystyle (b,a)} represents the rational number a / b {\displaystyle a/b} , and the slope of a segment connecting the origin of coordinates to this point is a / b {\displaystyle a/b} . Since a , b {\displaystyle a,b} are not required to be coprime , point ( b , a ) {\displaystyle (b,a)} represents one and only one rational number, but a rational number is represented by more than one point; e.g. ( 4 , 2 ) , ( 60 , 30 ) , ( 48 , 24 ) {\displaystyle (4,2),(60,30),(48,24)} are all representations of the rational number 1 / 2 {\displaystyle 1/2} . This is a slight modification of the formal definition of rational numbers, restricting them to positive values, and flipping the order of the terms in the ordered pair ( b , a ) {\displaystyle (b,a)} so that the slope of the segment becomes equal to the rational number.
Two points ( b , a ) ≠ ( d , c ) {\displaystyle (b,a)\neq (d,c)} where a , b , c , d ∈ N + {\displaystyle a,b,c,d\in \mathbb {N} ^{+}} are two representations of (possibly equivalent) rational numbers a / b {\displaystyle a/b} and c / d {\displaystyle c/d} . The line segments connecting the origin of coordinates to ( b , a ) {\displaystyle (b,a)} and ( d , c ) {\displaystyle (d,c)} form two adjacent sides in a parallelogram. The vertex of the parallelogram opposite to the origin of coordinates is the point ( b + d , a + c ) {\displaystyle (b+d,a+c)} , which is the mediant of a / b {\displaystyle a/b} and c / d {\displaystyle c/d} .
The area of the parallelogram is b c − a d {\displaystyle bc-ad} , which is also the magnitude of the cross product of vectors ⟨ b , a ⟩ {\displaystyle \langle b,a\rangle } and ⟨ d , c ⟩ {\displaystyle \langle d,c\rangle } . It follows from the formal definition of rational number equivalence that the area is zero if a / b {\displaystyle a/b} and c / d {\displaystyle c/d} are equivalent. In this case, one segment coincides with the other, since their slopes are equal. The area of the parallelogram formed by two consecutive rational numbers in the Stern–Brocot tree is always 1. [ 2 ]
The notion of mediant can be generalized to n fractions, and a generalized mediant inequality holds, [ 3 ] a fact that seems to have been first noticed by Cauchy. More precisely, the weighted mediant m w {\displaystyle m_{w}} of n fractions a 1 / b 1 , … , a n / b n {\displaystyle a_{1}/b_{1},\ldots ,a_{n}/b_{n}} is defined by ∑ i w i a i ∑ i w i b i {\displaystyle {\frac {\sum _{i}w_{i}a_{i}}{\sum _{i}w_{i}b_{i}}}} (with w i > 0 {\displaystyle w_{i}>0} ). It can be shown that m w {\displaystyle m_{w}} lies somewhere between the smallest and the largest fraction among the a i / b i {\displaystyle a_{i}/b_{i}} .
[1] | https://en.wikipedia.org/wiki/Mediant_(mathematics) |
Mediated transport refers to cellular transport mediated at the lipid bilayer through phospholipid interactions, or more frequently membrane transport proteins . Substances in the human body may be hydrophobic , electrophilic , contain a positively or negatively charge, or have another property. As such there are times when those substances may not be able to pass over the cell membrane using protein-independent movement. [ 1 ] The cell membrane is imbedded with many membrane transport proteins that allow such molecules to travel in and out of the cell. [ 2 ] There are three types of mediated transporters: uniport , symport , and antiport . Things that can be transported are nutrients, ions, glucose, etc, all depending on the needs of the cell. One example of a uniport mediated transport protein is GLUT1. GLUT1 is a transmembrane protein, which means it spans the entire width of the cell membrane, connecting the extracellular and intracellular region. It is a uniport system because it specifically transports glucose in only one direction, down its concentration gradient across the cell membrane.
Another example of a uniporter mediated transport protein is microsomal triglyceride transfer protein (MTTP) who is responsible for catalyzing the assembly of the triglyceride rich lipoproteins as well mediating their release from the lumen of the endoplasmic reticulum . What is distinguishable about this specific transfer protein is that it requires the protein PRAP1 to bind to the lipoprotein to facilitate the transport of said lipoprotein. MTTP only recognizes the PRAP1-lipoprotein complex and only then will it catalyze the transport reaction. [ 3 ] In a way, the PRAP1 protein acts as a signal for MTTP. The importance of such interactions implies that mediated transport is not only dependent on transmembrane proteins but can also require the presence of additional non-transmembrane proteins. For instance, studies show that in the absence of a fully functional PRAP1 protein, MTTP fails to transport specific lipoproteins across the endoplasmic reticulum membrane.
An example of a symporter mediated transport protein is SGLT1, a sodium/glucose co-transporter protein that is mainly found in the intestinal tract. The SGLT1 protein is a symporter system because it passes both glucose and sodium in the same direction, from the lumen of the intestine to inside the intestinal cells. [ 4 ]
An example of an antiporter mediated transport protein is the sodium-calcium antiporter, a transport protein involved in keeping the cytoplasmic concentration of calcium ions in the cells, low. This transport protein is an antiporter system because it transports three sodium ions across the plasma membrane in exchange for a calcium ion, which is transported in the opposite direction. [ 5 ]
Mechanism of transport . A molecule will bind to a transporter protein, altering its shape. The change of shape or other added substances such as ATP will, in turn, cause the transport protein to alter its shape and release the molecule onto the other side of the cell membrane. [ 7 ]
Source: [ 8 ]
The importance of mediated transport proteins is visualized with the presence of mutations that render the transport proteins nonfunctional. A prime example of this are mutations found within the Archain 1 gene which codes for the transport proteins COPI and COPII . The main function of these transport proteins is to facilitate the passage of molecules from the endoplasmic reticulum to the golgi apparatus , and vice versa. The mutated ARCN1 gene gives rise to abnormal COPI who fails to transport type I collagen and leads to the secretion of collagen. [ 10 ] Due to the fact that type I collagen is the main ingredient of connective tissue , such mutations are the cause of numerous severe skeletal disorders such as osteogenesis imperfecta and cranio-lenticulo-sutural dysplasia . Various variations of these disorders are characterized by visible physical dysplasia. This example highlights the importance of transport proteins, not only as a means for the passage of specific molecules across a membrane, but for proper bodily development. | https://en.wikipedia.org/wiki/Mediated_transport |
In the scale-free network theory ( mathematical theory of networks or graph theory ), a mediation-driven attachment (MDA) model appears to embody a preferential attachment rule tacitly rather than explicitly. According to MDA rule, a new node first picks a node from the existing network at random and connect itself not with that but with one of the neighbors also picked at random.
Barabasi and Albert in 1999 noted through their seminal paper [ 1 ] noted that (i) most natural and man-made networks are not static, rather they grow with time and (ii) new nodes do not connect with an already connected one randomly rather preferentially with respect to their degrees. The later mechanism is called preferential attachment (PA) rule which embodies the rich get richer phenomena in economics. In their first model, known as the Barabási–Albert model , Barabási and Albert (BA model) choose
where, Π ( i ) {\displaystyle \Pi (i)} is the probability that the new node picks a node i {\displaystyle i} from the labelled nodes of the existing network. It directly embodies the rich get richer mechanism.
Recently, Hassan et al. proposed a mediation-driven attachment model which appears to embody the PA rule but not directly rather in disguise. [ 2 ] In the MDA model, an incoming node choose an existing node to connect by first picking one of the existing nodes at random which is regarded as mediator. The new node then connect with one of the neighbors of the mediator which is also picked at random. Now the question is: What is the probability Π ( i ) {\displaystyle \Pi (i)} that an already existing node i {\displaystyle i} is finally picked to connect it with the new node? Say, the node i {\displaystyle i} has degree k i {\displaystyle k_{i}} and hence it has k i {\displaystyle k_{i}} neighbors. Consider that the neighbors of i {\displaystyle i} are labeled 1 , 2 , … , k i {\displaystyle 1,2,\ldots ,k_{i}} which have degrees k 1 , k 2 , … , k k i {\displaystyle k_{1},k_{2},\ldots ,k_{k_{i}}} respectively. One can reach the node i {\displaystyle i} from each of these k i {\displaystyle k_{i}} nodes with probabilities inverse of their respective degrees, and each of the k i {\displaystyle k_{i}} nodes are likely to be picked at random with probability 1 / N {\displaystyle 1/N} . Thus the probability Π ( i ) {\displaystyle \Pi (i)} of the MDA model is:
It can be re-written as
where the factor ∑ j = 1 k i 1 k j k i {\displaystyle {\frac {\sum _{j=1}^{k_{i}}{\frac {1}{k_{j}}}}{k_{i}}}} is the inverse of the harmonic mean (IHM) of degrees of the k i {\displaystyle k_{i}} neighbors of the node i {\displaystyle i} . Extensive numerical simulation suggest that for small m {\displaystyle m} the IHM value of each node fluctuate so wildly that the mean of the IHM values over the entire network bears no meaning. However, for large m {\displaystyle m} (specially m {\displaystyle m} approximately greater than 14) the distribution of IHM value of the entire network become left skewed Gaussian type and mean starts to have a meaning which becomes a constant value in the large m {\displaystyle m} limit. In this limit one finds that Π ( i ) ∝ k i {\displaystyle \Pi (i)\propto k_{i}} which is exactly the PA rule. It implies that the higher the links (degree) a node has, the higher its chance of gaining more links since they can be reached in a larger number of ways through mediators which essentially embodies the intuitive idea of rich get richer mechanism. Therefore, the MDA network can be seen to follow the PA rule but in disguise. Moreover, for small m {\displaystyle m} the MFA is no longer valid rather the attachment probability Π ( i ) {\displaystyle \Pi (i)} becomes super-preferential in character.
The idea of MDA rule can be found in the growth process of the weighted planar stochastic lattice (WPSL) . An existing node (the center of each block of the WPSL is regarded as nodes and the common border between blocks as the links between the corresponding nodes) during the process gain links only if one of its neighbor is picked not itself. It implies that the higher the links (or degree) a node has, the higher its chance of gaining more links since they can be reached in a larger number of ways. It essentially embodies the intuitive idea of PA rule. Therefore, the dual of the WPSL is a network which can be seen to follow preferential attachment rule but in disguise. Indeed, its degree distribution is found to exhibit power-law as underlined by Barabasi and Albert as one of the essential ingredients. [ 3 ] [ 4 ]
Degree distribution: The two factors that the mean of the IHM is meaningful and it is independent of N {\displaystyle N} implies that one can apply the mean-field approximation (MFA). That is, within this approximation one can replace the true IHM value β / m {\displaystyle \beta /m} of each node by their mean, where the factor m {\displaystyle m} that the number of edges the new nodes come with is introduced for latter convenience. The rate equation to solve then becomes exactly like that of the BA model and hence the network that emerges following MDA rule is also scale-free in nature. The only difference is that the exponent γ = 1 β ( m ) + 1 {\displaystyle \gamma ={{1} \over {\beta (m)}}+1} depends on m {\displaystyle m} where as in the BA model γ = 3 {\displaystyle \gamma =3} independent of m {\displaystyle m} .
In the growing network not all nodes are equally important. The extent of their importance is measured by the value of their degree k {\displaystyle k} . Nodes which are linked to an unusually large number of other nodes, i.e. nodes with exceptionally high k {\displaystyle k} value, are known as hubs. They are special because their existence make the mean distance, measured in units of the number of links, between nodes incredibly small thereby playing the key role in spreading rumors, opinions, diseases, computer viruses etc. [ 5 ] It is, therefore, important to know the properties of the largest hub, which we regard as the leader. Like in society, the leadership in a growing network is not permanent. That is, once a node becomes the leader, it does not mean that it remains the leader ad infinitum . An interesting question is: how long does the leader retain this leadership property as the network evolves? To find an answer to this question, we define the leadership persistence probability F ( τ ) {\displaystyle F(\tau )} that aleader retains its leadership for at least up to time τ {\displaystyle \tau } . Persistence probability has been of interest in many different systems ranging from coarsening dynamics to fluctuating interfaces or polymer chains.
The basic idea of the MDA rule is, however not completely new as either this or models similar to this can be found in a few earlier works, albeit their approach, ensuing analysis and their results are different from ours. For instance, Saramaki and Kaski presented a random-walk based model. [ 6 ] Another model proposed by Boccaletti et al. may appear similar to ours, but it markedly differs on closer look. [ 7 ] Recently, Yang {\it et al.} too gave a form for Π ( i ) {\displaystyle \Pi (i)} and resorted to mean-field approximation. [ 8 ] However, the nature of their expressions are significantly different from the one studied by Hassan et al. . Yet another closely related model is the Growing Network with Redirection (GNR) model presented by Gabel, Krapivsky and Redner where at each time step a new node either attaches to a randomly chosen target node with probability 1 − r {\displaystyle 1-r} , or to the parent of the target with probability r = 1 {\displaystyle r=1} . [ 9 ] The GNR model with r = 1 {\displaystyle r=1} may appear similar to the MDA model. However, unlike the GNR model, the MDA model is for undirected networks, and that the new link can connect with any neighbor of the mediator-parent or not. One more difference is that, in the MDA model new node may join the existing network with m {\displaystyle m} edges and in the GNR model it is considered m = 1 {\displaystyle m=1} case only. | https://en.wikipedia.org/wiki/Mediation-driven_attachment_model |
Mediator is a multiprotein complex that functions as a transcriptional coactivator in all eukaryotes . It was discovered in 1990 in the lab of Roger D. Kornberg , recipient of the 2006 Nobel Prize in Chemistry . [ 1 ] [ 2 ] Mediator [ a ] complexes interact with transcription factors and RNA polymerase II . The main function of mediator complexes is to transmit signals from the transcription factors to the polymerase. [ 3 ]
Mediator complexes are variable at the evolutionary, compositional and conformational levels. [ 3 ] The first image shows only one "snapshot" of what a particular mediator complex might be composed of, [ b ] but it certainly does not accurately depict the conformation of the complex in vivo . During evolution, mediator has become more complex. The yeast Saccharomyces cerevisiae (a simple eukaryote ) is thought to have up to 21 subunits in the core mediator (exclusive of the CDK module), while mammals have up to 26.
Individual subunits can be absent or replaced by other subunits under different conditions. Also, there are many intrinsically disordered regions in mediator proteins, which may contribute to the conformational flexibility seen both with and without other bound proteins or protein complexes. A more realistic model of a mediator complex without the CDK module is shown in the second figure. [ 4 ]
The mediator complex is required for the successful transcription by RNA polymerase II. Mediator has been shown to make contacts with the polymerase in the transcription preinitiation complex . [ 3 ] A recent model showing the association of the polymerase with mediator in the absence of DNA is shown in the figure to the left. [ 4 ] In addition to RNA polymerase II, mediator must also associate with transcription factors and DNA. A model of such interactions is shown in the figure to the right. [ 5 ] Note that the different morphologies of mediator do not necessarily mean that one of the models is correct; rather those differences may reflect the flexibility of mediator as it interacts with other molecules. [ c ] For example, after binding the enhancer and core promoter, the mediator complex undergoes a compositional change in which the kinase module dissociates from the complex to allow association with RNA polymerase II and transcriptional activation. [ 6 ]
The Mediator complex is located within the cell nucleus . It is required for the successful transcription of nearly all class II gene promoters in yeast. [ 7 ] It works in the same manner in mammals. The mediator functions as a coactivator and binds to the C-terminal domain of RNA polymerase II holoenzyme , acting as a bridge between this enzyme and transcription factors . [ 8 ]
The yeast mediator complex is approximately as massive as a small subunit of a eukaryotic ribosome . The yeast mediator is composed of 25 subunits, while the mammalian mediator complexes are slightly larger. [ 3 ] Mediator can be divided into 4 main parts: The head, middle, tail, and the transiently associated CDK8 kinase module. [ 10 ]
Mediator subunits have many intrinsically disordered regions called "splines", which may be important to allow the structural changes of the mediator that change the function of the complex. [ 3 ] [ d ] The figure shows how the splines of the Med 14 subunit connect a large portion of the complex together while still allowing flexibility. [ 4 ] [ e ]
Mediator complexes that lack a subunit have been found or produced. These smaller mediators can still function normally in some activity, but lack other capabilities. [ 3 ] This indicates a somewhat independent function of some of the subunits while being part of the larger complex.
Another example of structural variability is seen in vertebrates, in which 3 paralogues of subunits of the cyclin -dependent kinase module have evolved by 3 independent gene duplication events followed by sequence divergence. [ 3 ]
There is a report that mediator forms stable associations with a particular type of non-coding RNA , ncRNA-a. [ 11 ] [ f ] These stable associations have also been shown to regulate gene expression in vivo , and are prevented by mutations in MED12 that produce the human disease FG syndrome . [ 11 ] Thus, the structure of a mediator complex can be augmented by RNA as well as proteinaceous transcription factors. [ 3 ]
Mediator was originally discovered because it was important for RNA polymerase II function, but it has many more functions than just interactions at the transcription start site. [ 3 ]
Mediator is a crucial component for transcription initiation. Mediator interacts with the pre-initiation complex, composed of RNA Polymerase II and general transcription factors TFIIB, TFIID, TFIIE, TFIIF, and TFIIH to stabilize and initiate transcription. [ 12 ] Studies of Mediator-RNA Pol II contacts in budding yeast have emphasized the importance of TFIIB-Mediator contacts in the formation of the complex. Interactions of Mediator with TFIID in the initiation complex has been shown. [ 10 ]
The Structure of a core Mediator (cMed) that's associated with a core pre-initiation complex was elucidated. [ 12 ]
The preinitiation complex, which contains a mediator, transcription factors, a nucleosome [ 13 ] [ 14 ] [ g ] and RNA polymerase II, is important to position the polymerase for the start of transcription. Before RNA synthesis can occur, the polymerase must dissociate from mediator. This appears to be accomplished by phosphorylation of part of the polymerase by a kinase. Importantly, mediator and transcription factors do not dissociate from the DNA at the time polymerase begins transcription. Rather, the complex remains at the promoter to recruit another RNA polymerase to begin another round of transcription. [ 3 ] [ h ]
There is some evidence to suggest that mediator in a yeast is involved in regulating RNA polymerase III (Pol III) transcripts of tRNAs [ 15 ] In support of that evidence, an independent report showed specific association of mediator with Pol III in Saccharomyces cerevisiae . [ 16 ] Those authors also reported specific associations with RNA polymerase I and proteins involved in transcription elongation and RNA processing, supporting other evidence of mediator's involvement in elongation and processing. [ 16 ]
Mediator is involved in "looping" of chromatin , which brings distant regions of a chromosome into closer physical proximity. [ 3 ] The ncRNA-a mentioned above [ 11 ] is involved in such looping. [ i ] Enhancer RNAs (eRNAs) can function similarly. [ 3 ]
In addition to the looping of euchromatin , mediator appears to be involved in formation or maintenance of heterochromatin at centromeres and telomeres . [ 3 ]
TGFβ signaling at the cell membrane results in 2 different intracellular pathways . One of them depends on MED15, [ j ] while the other is independent of MED15. [ 17 ] In both human cells and Caenorhabditis elegans MED15 is involved in lipid homeostasis through the pathway involving SREBPs [ 18 ] In the model plant Arabidopsis thaliana the ortholog of MED15 is required for signaling by the plant hormone Salicylic acid, [ 19 ] while MED25 is required for the transcriptional activation of Hypoxia (environmental) , jasmonate and shade signalling responses. [ 20 ] [ 21 ] [ 22 ] [ 23 ] Two components of the CDK module (MED12 and MED13) are involved in the Wnt signaling pathway [ 3 ] MED23 is involved in RAS / MAPK/ERK pathway [ 3 ] This abbreviated review shows the versatility of individual mediator subunits, and leads to the idea that mediator is an end-point of signaling pathways. [ 3 ]
Involvement of mediator in various human diseases has been reviewed. [ 24 ] [ 25 ] [ 26 ] [ 27 ] [ 28 ] [ 29 ] [ 30 ] [ 31 ] [ 32 ] [ 33 ] [ 34 ] Since inhibiting one interaction of a disease-causing signaling pathway with a subunit of mediator may not inhibit general transcription needed for normal function, mediator subunits are attractive candidates for therapeutic drugs. [ 3 ]
A method employing very gentle cell lysis in yeast followed by co- immunoprecipitation with an antibody to a mediator subunit (Med 17) has confirmed almost all previously reported or predicted interactions and revealed many previously unsuspected specific interactions of various proteins with mediator. [ 16 ]
A discussion of all mediator subunits is beyond the scope of this article, but details of one of the subunits are illustrative of the types of information that may be gathered for other subunits.
Micro RNAs are involved in regulating the expression of many proteins. Med1 is targeted by miR-1, which is important in gene regulation in cancers. [ 35 ] The tumor suppressor miR-137 also regulates MED1. [ 36 ]
Null mutants die at an early gestational age (embryonic day 11.5). [ 37 ] [ 38 ] By investigating hypomorphic mutants (which can survive 2 days longer), it was found that placental defects were primarily lethal and that there were also defects in cardiac and hepatic development, but many other organs were normal [ 38 ]
Conditional mutations can be produced in mice which affect only specific cells or tissues at specific times, so that the mouse can develop to adulthood and the adult phenotype can be studied. In one case, MED1 was found to participate in controlling the timing of events of meiosis in male mice. [ 39 ] Conditional mutants in keratinocytes show differences in skin wound healing. [ 40 ] A conditional mutant in mice was found to change dental epithelium into epidermal epithelium, which caused hair to grow associated with the incisors. [ 41 ]
The Mediator complex is composed at least 31 subunits in all eukaryotes studied: MED1 , MED4 , MED6 , MED7 , MED8 , MED9 , MED10 , MED11 , MED12 , MED13 , MED13L, MED14 , MED15 , MED16 , MED17 , MED18 , MED19 , MED20 , MED21 , MED22 , MED23 , MED24 , MED25 , MED26 , MED27 , MED28 , MED29 , MED30 , MED31 , CCNC , and CDK8 . There are three fungal-specific components, referred to as Med2 , Med3 and Med5 . [ 42 ]
The subunits form at least three structurally distinct submodules. The head and the middle modules interact directly with RNA polymerase II, whereas the elongated tail module interacts with gene-specific regulatory proteins . Mediator containing the CDK8 module is less active than Mediator lacking this module in supporting transcriptional activation .
Below is a cross-species comparison of mediator complex subunits. [ 42 ] [ 43 ] | https://en.wikipedia.org/wiki/Mediator_(coactivator) |
Medicago Inc. was a Canadian biotechnology company focused on the discovery, development, and commercialization of virus-like particles using plants as bioreactors to produce proteins, candidate vaccines , and medications . By using live plant leaves as hosts in the discovery and manufacturing process, the Medicago " Proficia " technology intended to create a rapid, high-yield system for its product candidates. Privately owned by a subsidiary of Mitsubishi Tanabe Pharma , Medicago and its product development programs were terminated by Mitsubishi in February 2023. [ 1 ]
The main clinical targets for Medicago product candidates were antiviral vaccines and antibody therapeutics. [ 2 ] The company's name was derived from the Latin word for alfalfa , which was the first plant the company used to develop its technologies. [ 3 ] Medicago technologies evolved from research at the Laval University and Agriculture and Agri-Food Canada in the 1990s.
A research partnership was formed between Laval University and Agriculture Canada in 1997. This would go on to be incorporated in 1999 as Medicago, licensing that technology researched in the partnership, from Agriculture Canada and Université Laval. [ 4 ]
In September 2013, Philip Morris International acquired a 40% stake in Medicago, the remaining 60% being acquired by Mitsubishi Tanabe Pharma Corporation and other Mitsubishi Group companies, in a joint purchase. [ 5 ] [ 6 ]
The company had a Phase III clinical trial underway in 2020 for its candidate to prevent seasonal influenza . [ 2 ]
For its COVID-19 vaccine, Medicago grew its virus-like particles in the Australian weed, Nicotiana benthamiana . [ 7 ] In July 2020, the company began a Phase I clinical trial on its candidate vaccine for COVID-19 disease , coVLP , [ 8 ] [ 9 ] which advanced to a Phase II-III trial in Canada and the United States during November 2020. [ 10 ] [ 11 ] The Canadian government invested $173 million into Medicago to support development of the Covifenz vaccine and help expand its production facility. [ 12 ] In December 2021, the company announced that its CoVLP vaccine candidate exhibited 71% efficacy and no adverse effects in a multinational, Phase III clinical trial . [ 13 ] In February 2022, Health Canada authorized use of CoVLP (brand name Covifenz ) for preventing COVID-19 infection in adults 18 to 64 years old. [ 14 ]
In July 2022, the Canadian federal government determined it would not consider buying the shares owned by Medicago's parent company, tobacco company Philip Morris International , to overcome the problem of the World Health Organization accepting any products from tobacco concerns. [ 15 ]
In December 2022, Philip Morris was bought out by Mitsubishi, acquiring a 100% stake in the company. [ 16 ]
In February 2023, Mitsubishi Chemical Corporation decided to shut down the company due to the changing landscape of COVID-19 vaccines and the marketplace, and the low commercial prospects of the company. [ 1 ] [ 17 ]
The Medicago technology used plants as bioreactors to produce proteins for vaccine and protein-based therapeutic candidates. [ 18 ] The plant-based production platform was intended to be accurate and rapid to shorten product development time and prevent the risk of mutation . [ 18 ]
Medicago used its proprietary Proficia technology, which is a possible alternative to traditional egg-based methods for producing virus-like particles (VLPs) used to manufacture vaccine candidates. [ 19 ] [ 18 ] Typically, licensed influenza vaccines are manufactured using embryonated chicken eggs . [ 20 ] With living plants as hosts, Proficia technology used VLP production as antigens in plant leaves, providing a flexible, high-yield system with potential to produce test material within the growth period of plants (one month). [ 18 ]
The steps of the technology are:
VLPs serve as potential vaccines by mimicking the natural structure and function of viruses, enabling recognition by the immune system . [ 18 ] However, by absence of the main virus genetic material, VLPs are non-infectious and unable to replicate like a virus does in vivo , thereby evoking an immune response similar to a natural infection, but without the associated illnesses. [ 18 ]
The lead COVID-19 vaccine candidate, CoVLP , by Medicago, was a coronavirus VLP grown in the Australian weed, Nicotiana benthamiana . [ 7 ] [ 8 ] [ 11 ]
Medicago was developing the COVID-19 vaccine candidate in collaboration with the governments of Canada and Quebec , [ 3 ] and by using an adjuvant manufactured by GlaxoSmithKline . [ 21 ]
As of August 2020, the Medicago vaccine candidate was being evaluated for safety, toxicity, and immune response in a Phase I clinical trial at two locations in Quebec. [ 9 ] In October 2020, the Government of Canada awarded Medicago a contract of up to $173 million to advance the company's COVID-19 vaccine candidate. [ 22 ]
In November 2020, Medicago-GSK started Phase II-III clinical trials for their COVID-19 vaccine candidate. [ 11 ] [ 23 ]
As of January 2021, the Phase III trial was enrolling participants toward the total goal of 30,612, with each volunteer receiving two injections 21 days apart in an amount of 3.75 micrograms of CoVLP each time. [ 24 ] The Phase III study is scheduled to conclude in April 2022. [ 24 ] In December 2021, the CoVLP candidate showed 71% efficacy and safety in preliminary results from the Phase III trial. [ 13 ]
In February 2022, Medicago and GlaxoSmithKline received authorization for CoVLP from Health Canada as an approved vaccine for preventing COVID-19 infection in adults 18 to 64 years old. [ 14 ] The brand name for CoVLP is Covifenz . [ 25 ]
In March 2022, the first Canadian-made COVID-19 vaccine produced by Medicago was rejected by the World Health Organization due to the tobacco company Philip Morris International owning a stake in the company. [ 26 ] The UN agency has a strict policy about engagement with the tobacco industry. [ 15 ]
Due to substantial competition in the global vaccine market and low demand for Covifenz , Mitsubishi announced in February 2023 that Covifenz and Medicago, Inc. would be terminated. [ 1 ]
Aramis Biotechnologies [ 27 ] was set up as a successor company to Medicago during 2023, acquiring intellectual property and equipment, in agreement with Mitsubishi Chemical Group. [ 28 ] [ 29 ] | https://en.wikipedia.org/wiki/Medicago_Inc. |
Medical Devices Park, Hyderabad is a medical devices industrial estate located in Hyderabad , Telangana , India . [ 1 ] The largest such Park in India spread over 250 acres. [ 2 ] [ 3 ] The dedicated park's ecosystem supports medical technology innovation and manufacturing.
The Park was inaugurated on 17 June 2017 near Hyderabad at Sultanpur in Patancheru of Sangareddy district by the Minister for Industries, K. T. Rama Rao . [ 4 ] | https://en.wikipedia.org/wiki/Medical_Devices_Park,_Hyderabad |
The Medical Waste Tracking Act of 1988 was a United States federal law concerning the illegal dumping of body tissues, blood wastes and other contaminated biological materials. It established heavy penalties for knowingly endangering life through noncompliance. The law expired in 1991.
The law created a two-year program that went into effect in New York , New Jersey , Connecticut , Rhode Island and Puerto Rico on June 24, 1989, and expired on June 21, 1991. [ 1 ] [ 2 ]
The H.R. 3515 legislation was passed by the 100th Congressional session and signed into law by the 40th President of the United States Ronald Reagan on November 2, 1988. [ 3 ]
Beginning on August 13, 1987, a "30-mile garbage slick" composed primarily of medical and household wastes prompted extensive closures of numerous New Jersey and New York beaches . [ 4 ] Investigations ongoing throughout the year indicated that the waste likely originated from " New York City 's marine transfer stations … and the Southwest Brooklyn Incinerator and Transfer Station in particular…" [ 2 ] The then-assistant commissioner of the New Jersey Department of Environmental Protection stated his belief that the cause of pollution was intentional rather than accidental; "sealed plastic garbage bags , he said, were cut at the top, so their contents could disperse through the ocean." [ 4 ] Such a deliberate action may have arisen given the high cost (~$1500/ton) associated with the legal disposal of the waste, thus incentivizing private waste contractors to dump illegally to avoid high fees.
Ultimately the Medical Waste Tracking Act of 1988 (MWTA) arose from the aftermath of this situation. It was designed primarily to monitor the treatment of medical wastes through their creation, transportation and destruction, i.e. from "cradle-to-grave." Congress approved the bill "to amend the Solid Waste Disposal Act to require the Administrator of the Environmental Protection Agency (EPA) to promulgate regulations on the management of infections waste." [ 5 ] In short, Congress enacted the MWTA as a pilot study to better determine how the life cycle of medical wastes played out under federal regulations .
Section 11002 of the MWTA, "Listing of Medical Wastes," provides a listing of definitions on what materials will be classified as "medical wastes" under the act. [ 5 ] The list includes within its definitions: "cultures and stocks of infectious agents ," "pathological wastes" such as body tissues , blood wastes and blood byproducts, sharps , contaminated carcasses and beddings of animals, surgery or autopsy wastes that were once in contact with infectious agents, "laboratory wastes," "dialysis wastes that were in contact with the blood of patients undergoing hemodialysis ," medical equipment having come in contact with infectious agents, and further contaminated biological materials. [ 2 ] Defining what objects were to be classified as medical wastes was crucial to ensure that all municipalities under the MWTA would be monitoring similar materials.
Section 11003, "Tracking of Medical Waste," outlined how the program should manage the transportation of waste materials . [ 2 ] Four requirements were primarily identified; first, to provide a means of monitoring "the transportation of waste from the generator to the disposal facility" unless said waste had previously been incinerated . Secondly, to be able to ensure the "generator of the waste" that the waste had been "received by the disposal facility." Next to develop a uniform form for the tracking of materials across states and finally to develop a means to label and contain the wastes for the safety of the handlers.
Following this, Section 11004 on "Inspections" provides provisions allowing for agents of the EPA to "enter… any establishment… where medical wastes are or have been generated" so as to conduct "monitoring", "testing", or to "obtain samples from any person.". [ 5 ] This process would allow for the Agency to legally enter generating facilities for the purpose of determining if infectious agents and materials were being handled as prescribed by the EPA Administrator.
A major point of importance within the MWTA involves its inclusion of enforcement laws within the legislation . This becomes notable as it allows for one of the first instances in which an agency of the federal government may prosecute those charged with violation of regulations dealing with medical wastes. Following enactment of the MWTA the EPA Administrator may be allowed to "commence civil action in the United States district court in the district in which the violation occurred" against those being charged with the violation.
Penalties ranged based on the level of violation, whether it was done with intention, and if such acts endangered the lives of other individuals. Minor violations of compliance orders would have resulted in a fine of $25,000 per day of "continued noncompliance." Criminal penalties against those knowingly and intentionally violating the regulations of the MWTA may face two years of imprisonment or a $50,000 fine while those guilty of knowingly endangering the life of another through noncompliance may face upwards of fifteen years imprisonment and a $1,000,000 fine.
Through the information gathered during the promulgation of regulations for the MWTA, over a period of ten years the EPA eventually "concluded that the disease -causing potential of medical waste is greatest at the point of generation and naturally tapers off after that point... Thus, risk to the general public of disease caused by exposure to medical waste is likely to be much lower than risk for the occupationally exposed individual." [ 2 ]
After expiration of the MWTA, state environmental and health agencies have continued to regulate medical waste, rather than EPA. Other federal agencies have issued safety regulations governing the handling of medical waste, including the Centers for Disease Control and Prevention , Occupational Safety and Health Administration , and the Food and Drug Administration . [ 2 ] | https://en.wikipedia.org/wiki/Medical_Waste_Tracking_Act |
Medical biology is a field of biology that has practical applications in medicine , health care , and laboratory diagnostics . It includes many biomedical disciplines and areas of specialty that typically contains the "bio-" prefix such as:
Medical biology is the cornerstone of modern health care and laboratory diagnostics . It concerned a wide range of scientific and technological approaches: from in vitro diagnostics [ 1 ] [ 2 ] to in vitro fertilisation , [ 3 ] from the molecular mechanisms of cystic fibrosis to the population dynamics of HIV , from understanding molecular interactions to the study of carcinogenesis , [ 4 ] from a single-nucleotide polymorphism (SNP) to gene therapy .
Medical biology based on molecular biology, combines all issues of developing molecular medicine [ 5 ] into large-scale structural and functional relationships of the human genome , transcriptome , proteome and metabolome, with a particular focus on devising new technologies for prediction, diagnosis, and therapy. [ 6 ] | https://en.wikipedia.org/wiki/Medical_biology |
The medical examiner is an appointed official in some American jurisdictions [ 1 ] who is trained in pathology and investigates deaths that occur under unusual or suspicious circumstances, to perform post-mortem examinations , and in some jurisdictions to initiate inquests . [ 2 ] [ 3 ]
In the US, there are two death investigation systems: first, the coroner system based on English law ; and second, the medical examiner system, which evolved from the coroner system during the latter half of the 19th century. The type of system varies across jurisdictions, with over 2,000 separate jurisdictions for investigating unnatural deaths . In 2002, 22 states had a medical examiner system, 11 states had a coroner system, and 18 states had a mixed system. Since the 1940s, the medical examiner system has gradually replaced the coroner system and serves about 48% of the US population. [ 4 ] [ 5 ] The largest medical examiner's office in the United States is located in Baltimore , Maryland . [ 6 ]
The coroner is not necessarily a medical doctor . They may be a lawyer or a layperson. In the 19th century, the public became dissatisfied with lay coroners and demanded that the coroner be replaced by a physician. In 1918, New York City introduced the office of the Chief Medical Examiner and appointed physicians experienced in the field of pathology. In 1959, the medical subspecialty of forensic pathology was formally certified. [ 7 ]
The types of death reportable to the system are determined by federal, state, or local laws. Commonly, these include violent, suspicious, sudden, and unexpected deaths, death when no physician or practitioner was present or treating the decedent, inmates in public institutions, those in custody of law enforcement , deaths during or immediately following therapeutic or diagnostic procedures or deaths due to neglect .
A medical examiner's duties vary by location, but typically include:
In some jurisdictions , a coroner performs these and other duties. It is common for a medical examiner to visit crime scenes or to testify in court . [ 8 ] Medical examiners specialize in forensic knowledge and rely on this during their work. [ 3 ] In addition to studying cadavers , they are also trained in toxicology , DNA technology and forensic serology (blood analysis). [ 8 ] Pulling from each area of knowledge, a medical examiner is an expert in determining a cause of death. [ 3 ] This information can help law enforcement solve cases and is crucial to their ability to track criminals in the event of a homicide or other related events. [ 3 ]
Within the United States, there is a mixture of coroner and medical examiner systems, and in some states, dual systems. The requirements to hold office vary widely between jurisdictions.
In England and Wales , a new statutory Medical Examiner system based in NHS Acute Trusts commenced in 2019 and is expected to be fully operational several years later. A medical examiner is always a medical doctor , whereas a coroner is a judicial officer . [ 9 ]
Pilot studies in Sheffield and seven other areas, which involved medical examiners looking at more than 27,000 deaths since 2008, found 25% of hospital death certificates were inaccurate and 20% of causes of death were wrong. Suzy Lishman , president of the Royal College of Pathologists , said it was crucial there was "independent scrutiny of causes of death". [ 10 ]
Qualifications for medical examiners in the US vary from jurisdiction to jurisdiction. In Wisconsin , for example, some counties do not require individuals to have any special educational or medical training to hold this office. [ 11 ] In most jurisdictions, a medical examiner is required to have a medical degree , although in many there is no requirement for specialized training in pathology. Other jurisdictions have stricter requirements, including additional education in pathology , law, and forensic pathology . Medical examiners are typically appointed officers. [ 1 ]
In the United States, medical examiners require extensive training in order to become experts in their field. [ 8 ] After high school, the additional schooling may take 11–18 years. [ 8 ] They must attend a college or university to earn a bachelor's degree sufficient for admission to medical school. [ 3 ] Biology is usually the most common. [ 12 ] A medical degree (MD or DO) is often required to become a medical examiner. [ 13 ] [ 12 ] To enter medical school, the MCAT (Medical College Admissions Test) is usually required [ 3 ] after which medical school is another four years with the first two dedicated to academics and the rest of the two used to gain clinical experience. [ 12 ]
To become experts in pathology, specifically, additional training is required after medical school. The first step is to complete pathological forensic training. [ 13 ] This usually consists of anatomic and clinical pathology training which takes anywhere from four to five years to complete. [ 3 ] After this, the physician may complete an anatomic pathology residency or a fellowship . [ 12 ] Before practicing as a medical examiner, the physician must also become board certified through the American Board of Pathology . [ 13 ] [ 14 ]
The general job outlook for medical examiners in the United States is considered to be excellent. [ 8 ] Remuneration varies by location, but it is estimated to average between $105,000 and $500,000. [ 8 ]
In the United States, there are fewer than 500 board-certified forensic pathologists, but the National Commission on Forensic Science estimates the country needs 1,100–1,200 to perform the needed number of autopsies. The shortage is attributed to the nature of the work and the higher pay in other medical specialties. It has caused long delays in some states and resulted in fewer investigations and less thorough investigations in some cases. [ 15 ] | https://en.wikipedia.org/wiki/Medical_examiner |
Medical gas supply systems in hospitals and other healthcare facilities are utilized to supply specialized gases and gas mixtures to various parts of the facility. Products handled by such systems typically include:
Source equipment systems are generally required to be monitored by alarm systems at the point of supply for abnormal (high or low) gas pressure in areas such as general ward, operating theatres, intensive care units, recovery rooms, or major treatment rooms. Equipment is connected to the medical gas pipeline system via station outlets (US) or terminal units (ISO) .
Medical gas systems are commonly color coded to identify their contents, but as coding systems and requirements (such as those for bottled gas ) vary by jurisdiction, the text or labeling is the most reliable guide to the contents. Emergency shut-off valves, or zone valves, are often installed in order to stop gas flowing to an area in the event of fire or substantial leak, as well as for service. Valves may be positioned at the entrance to departments, with access provided via emergency pull-out windows.
Oxygen may be used for patients requiring supplemental oxygen via mask. Usually accomplished by a large storage system of liquid oxygen at the hospital which is evaporated into a concentrated oxygen supply, pressures are usually around 345–380 kPa (50.0–55.1 psi), [ 1 ] [ 2 ] or in the UK and Europe, 4–5 bar (400–500 kPa; 58–73 psi). [ 3 ] This arrangement is described as a vacuum insulated evaporator or bulk tank. [ 4 ] In small medical centers with a low patient capacity, oxygen is usually supplied by a manifold of multiple high-pressure cylinders. In areas where a bulk system or high-pressure cylinder manifold is not suitable, oxygen may be supplied by an oxygen concentrator . However, on site production of oxygen is still a relatively new technology.
Medical air is compressed air supplied by a special air compressor , through a dryer (in order to maintain correct dew point levels), and distributed to patient care areas by half hard BS:EN 13348 copper pipe and also use isolation ball valve for operating the services of compressed air 4 bar. It is also called medical air 4 bar. In smaller facilities, medical air may also be supplied via high-pressure cylinders. Pressures are maintained around 345–380 kPa (50.0–55.1 psi). If not used correctly it can be harmful to humans. [ 5 ]
Nitrous oxide is supplied to various surgical suites for its anaesthetic functions during preoperative procedures. It is delivered to the hospital in high-pressure cylinders and supplied through the Medical Gas system. Some bulk systems exist, but are no longer installed due to environmental concerns and overall reduced consumption of nitrous oxide. System pressures are around 345 kPa (50.0 psi), 4 bar (400 kPa; 58 psi) UK.
Nitrogen is typically used to power pneumatic surgical equipment during various procedures, and is supplied by high-pressure cylinders. Pressures range around 1.2 MPa (170 psi) to various locations.
Like nitrogen, instrument air is used to power surgical equipment. However, it is generated on site by an air compressor (similar to a medical air compressor) rather than high-pressure cylinders. Early air compressors could not offer the purity required to drive surgical equipment. However, this has changed and instrument air is becoming a popular alternative to nitrogen. As with nitrogen, pressures range around 1.2 MPa (170 psi). UK systems are supplied at 11 bar (1.1 MPa; 160 psi) to the local area and regulated down to 7–8 bar (700–800 kPa; 100–120 psi) at point of use.
This gas is typically used pure for insufflation during surgery, but can also be used in its liquid form for cryotherapy or local analgesia . Mixed with other gases, it can be used for sterilisation of equipment, anaesthesia , and stimulation of the respiratory system. [ 6 ]
A mixture of 5% carbon dioxide in oxygen is called carbogen and is used in the investigation and treatment of various respiratory conditions, such as to stimulate breathing after a period of apnoea, and managing chronic respiratory obstruction. [ 6 ]
Medical vacuum in a hospital supports suction equipment and evacuation procedures, supplied by vacuum pump systems exhausting to the atmosphere. Vacuum will fluctuate across the pipeline, but is generally maintained around −75 kPa (−560 mmHg; −22 inHg), −450 mmHg (−60 kPa; −18 inHg) UK.
Waste anaesthetic gas disposal, or anaesthetic gas scavenging system, is used in hospital anaesthesia evacuation procedures . Although it is similar to a medical vacuum system, some building codes require anaesthetic gases to be scavenged separately. Scavenging systems do not need to be as powerful as medical vacuum systems, and can be maintained around −50 to −65 kPa (−380 to −490 mmHg; −15 to −19 inHg).
There are many gas mixtures used for clinical and medical applications. They are often used for patient diagnostics such as lung function testing or blood gas analysis. Test gases are also used to calibrate and maintain medical devices used for the delivery of anaesthetic gases. In laboratories, culture growth applications include controlled aerobic or anaerobic incubator atmospheres for biological cell culture or tissue growth. Controlled aerobic conditions are created using mixtures rich in oxygen and anaerobic conditions are created using mixtures rich in hydrogen or carbon dioxide. Supply pressure is 4 bar (400 kPa; 58 psi).
Two common medical gas mixtures are entonox and heliox . | https://en.wikipedia.org/wiki/Medical_gas_supply |
Medical gas therapy is a treatment involving the administration of various gases. It has been used in medicine since the use of oxygen therapy . [ 1 ] Most of these gases are drugs, including oxygen. [ 2 ] Many other gases, collectively known as factitious airs , were explored for medicinal value in the late eighteenth century. In addition to oxygen, medical gases include nitric oxide (NO), and helium-O2 mixtures (Heliox). Careful considerations and close monitoring needed when medical gases are in use. For the purpose of this article only gas mixtures are described.
Nitric oxide is a substance that our body produces in its every cell and in its every organ. It has a number of functions. It take part in vasodilation, platelet inhibition, immune regulation, enzyme regulation, and neurotransmission.
Inhaled nitric oxide is a gas that is inhaled. [ 1 ] It was initially described in 1987 as an "endothelial-derived relaxing factor" and has since been used to treat pulmonary disorders. [ 3 ] It works by relaxing smooth muscle to widen (dilate) blood vessels , especially in the lungs. [ 1 ] Inhaled nitric oxide selects only pulmonary smooth muscles. There will be no effect or minimal effect of inhaled nitric oxide on atelectatic or fluid-filled lung. [ 3 ] It improves oxygenation and decreases pulmonary hypertension . [ 4 ] Nitric oxide is used together with a mechanical ventilator to treat respiratory failure in premature infants . [ 1 ] In adults nitric oxide can be used in treating pulmonary hypertension with acute respiratory distress syndrome . Thanks to the possible clinical successful outcomes of nitric oxide treatment patients can avoid need for extracorporeal membrane oxygenation treatment. The U.S. Food and Drug Administration has been approved the use of nitric oxide in term and near-term (greater than 34 weeks' gestation age) neonates with hypoxic respiratory failure with clinical or echocardiographic evidence of pulmonary hypertension. [ 5 ]
Nitric oxide must not be used in neonates who depend on right-to-left shunting of blood.
Dose needed to achieve desired effect but avoid toxicity and adverse effects in neonates and adults is relatively low. Usually it is 5-20 ppm (parts per million). [ 6 ] Regular arterial blood gas tests needed to assess the response to the therapy and signs of toxicity. Improvement in partial pressure of oxygen (PO2) and oxygen saturation would be indication of positive response to the nitric oxide therapy. If there is an evidence that nitric oxide works the same dose would be used till the hypoxemia and pulmonary hypertension resolved. When the hypoxemia and pulmonary hypertension resolved titration or slowly weaning of the nitric oxide initiates. Abrupt discontinuation of nitric oxide may lead to compromised oxygenation and pulmonary hypertension may rebound. [ 7 ]
Methemoglobins level in the blood increases with the use of nitric oxide. Methemoglobin is abnormal form of molecule which can not carry oxygen. Methemoglobin turns blood brown. Other medications can produce methemoglobin too. Monitoring of methemoglobin needed when nitric oxide is in use.
Nitric oxide with oxygen ( O 2 ) in combination produces another by-product chemical compound nitrogen dioxide ( NO 2 ). The higher the oxygen concentration and nitric oxide therapy duration and lower ventilator flow rate the higher amount of NO 2 will be produced. NO 2 is toxic and its level should always be monitored in nitric oxide therapies. High level of NO 2 can lead to cell damage, hemorrhage, pulmonary edema .
Use of nitric oxide in patients with left heart failure or congestive heart failure may lead to pulmonary edema or worsen pulmonary edema.
Three US scientist - Robert F. Furchgott, PhD, Louis J. Ignarro, PhD, and Ferid Murad, MD, PhD won Nobel Prize in Physiology and Medicine for their discovery of nitric oxide role in cardiovascular and nervous systems in 1998. [ 8 ] Even though the nitric oxide effects on the body known for more than 25 years the clinical use is still in a development.
In medicine, Heliox generally refers to a mixture of 21% O 2 (the same as air ) and 79% He, although other combinations are available.
Heliox generates less airway resistance than air and thereby requires less mechanical energy to ventilate the lungs. [ 9 ] "Work of Breathing" is reduced. It does this by two mechanisms:
The dry air on the Earth we inhale consists of 78.8% nitrogen, 20.95% oxygen and 0.93% argon. Heliox therapy is substitution of nitrogen with helium. Helium itself has no pharmacological value, it does not react in the body. Its only purpose is to make the flow less turbulent and help oxygen to get into the lungs. Less turbulent flow requires less work to breathe.
Helium (He) is colorless, odorless, tasteless, and inert noble gas. Helium is second lightest gas after hydrogen. [ 10 ]
Heliox has a similar viscosity to air but a significantly lower density (0.5 g/L versus 1.2 5g/L at STP ). Flow of gas through the airways comprises laminar flow , transitional flow and turbulent flow . The tendency for each type of flow is described by the Reynolds number . Heliox 's low density produces a lower Reynolds number and hence higher probability of laminar flow for any given airway. Laminar flow tends to generate less resistance than turbulent flow.
In the small airways where flow is laminar, resistance is proportional to gas viscosity and is not related to density and so heliox has little effect. The Hagen–Poiseuille equation describes laminar resistance. In the large airways where flow is turbulent, resistance is proportional to density, so Heliox has a significant effect.
Heliox has been used medically since the early 1930s. It was the mainstay of treatment in acute asthma before the advent of bronchodilators . Currently, heliox is mainly used in conditions of large airway narrowing (upper airway obstruction from tumors or foreign bodies and vocal cord dysfunction ). There is also some use of heliox in conditions of the medium airways ( croup , asthma and chronic obstructive pulmonary disease ).
Patients with these conditions may develop a range of symptoms including dyspnea (breathlessness), hypoxemia (below-normal oxygen content in the arterial blood) and eventually a weakening of the respiratory muscles due to exhaustion , which can lead to respiratory failure and require intubation and mechanical ventilation . Heliox may reduce all these effects, making it easier for the patient to breathe. [ 11 ] Heliox has also found utility in the weaning of patients off mechanical ventilation, and in the nebulization of inhalable drugs, particularly for the elderly. [ 12 ] Research has also indicated advantages in using helium–oxygen mixtures in delivery of anaesthesia . [ 13 ]
Heliox side effect is that inhaled helium change voice. Speech will sound high pitched. This effect is caused by low density gas passing through the vocal cords. The effect is reversible. | https://en.wikipedia.org/wiki/Medical_gas_therapy |
Medical geology is an interdisciplinary scientific field studying the relationship between natural geological factors and their effects on human and animal health . [ 1 ] The Commission on Geological Sciences for Environmental Planning defines medical geology as "the science dealing with the influence of ordinary environmental factors on the geographical distribution of health problems in man and animals." [ 2 ]
Many have deemed medical geology as a new field, when in actuality it is re-emerging. Hippocrates and Aristotle first recognized the relationship between human diseases and the earth's elements. [ 4 ] This field ultimately depends on a number of different fields coming and working together to solve some of the earth's mysteries. The scientific term for this field is hydrobiogeochemoepidemiopathoecology ; [ 5 ] however, it is more commonly known as medical geology. [ 4 ] It was established in 1990 by the International Union of Geological Sciences. [ 2 ] Paracelsus , the "father of pharmacology " (1493–1541), stated that "all substances are poisons, there is none which is not a poison. The right dosage differentiates a poison and a remedy." [ 2 ] This passage sums up the idea of medical geology. The goal of this field is to find the right balance and intake of elements/minerals in order to improve and maintain health. [ 2 ]
Examples of research in medical geology include: [ citation needed ]
Recently, a new concept of "geomedical engineering" has been introduced in medical geology through a paper titled "Geomedical Engineering: A new and captivating prospect". [ 6 ] It provides the fundamentals of engineering applications to the medical geology issues. [ 7 ]
It is widely known that the state of our environment affects us in many ways. Minerals and rocks have an impact on human and animal populations because that is what the earth is composed of. [ 2 ] Medical geology brings professionals from both the medicine field and the geology field to help us understand this relationship. [ 8 ] There are two priorities that have been established within the medical geology field, "(1) the study of trace elements , especially their bioavailability and (2) a need to establish baseline, or background levels of contaminants / xenobiotics /potentially harmful but naturally occurring materials in water , soil , air , food , and animal tissue." [ 4 ] The elements and minerals in the land affect people and animals immensely, especially when there is a close relationship between the two. Those who depend heavily on the land are faced with one of two problems. First, those who live in places such as Maputaland , South Africa are exposed to heavily impoverished soils which result in a number of diseases caused by mineral imbalances. [ 2 ] Secondly, those in areas such as India and Bangladesh are often exposed to an excess of elements in the land, resulting in mineral toxicity . [ 2 ]
All living organisms need some naturally occurring elements ; however, excessive amounts can be detrimental to health . [ 9 ] There is a direct link between health and the earth because all humans ingest and breath in these chemicals and for the most part it is done unknowingly. [ 9 ]
There are many ways in which humans come into contact with the earth's elements and below are only a few ways in which we become exposed to them.
One of the biggest geochemical diseases is iodine deficiency . Thirty percent of the world is at risk for it and insufficient intake is the most common cause of intellectual disability and brain damage . [ 2 ] The sea is a major source of iodine and those who are further from it are at a disadvantage. [ 2 ] Another source of it is in soil ; however, goitrogens such as humus and clay trap the iodine , making it hard for people to access it. [ 2 ] Some cultures actually consume the earth's minerals by eating soil and clay ; this is known as geophagy. [ 2 ] It is most common in the tropics, especially among pregnant women. [ 2 ] The Ottomac people of South America engage in this practice and none have suffered from any health problems related with mineral/ Iodine deficiency. [ 2 ]
Cardiovascular disease has often been linked to water hardness as the main cause. [ 2 ] Water hardness means that there is magnesium in the water with calcium playing a role. [ 2 ] Some research has completely discredited this evidence, and has found that the more magnesium in the water the less chance of death cardiovascular disease. [ 2 ]
Natural radiation is found everywhere; it is in the air , water , soil , rocks, minerals and food . [ 2 ] The largest amount of radiation comes from radon . [ 2 ] Certain places are called 'high background radiation areas' (HBRAs), such as Guarapari , Southwest of France , Ramsar , parts of China , and Kerala Coast. [ 2 ] People living in these areas however have not shown any health deficiencies and in some cases are even healthier and live longer than those not in HBRAs. [ 2 ]
Among the problems presented there are also issues with fluoride in Africa and India , arsenic in Argentina , Chile , and Taiwan , selenium in areas of the United States , Venezuela , China and nitrate in agricultural areas. [ 10 ] As medical geology grows it may become more important to the medical field in relation to the issue of diseases .
In addition to deficiencies of particular minerals, dietary excesses of certain elements occurring in specific geographic regions can also be harmful to human health, as per the examples listed below:
"The International Medical Geology Association (IMGA) aims to provide a network and a forum to bring together the combined expertise of geologists and earth scientists, environmental scientists, toxicologists , epidemiologists , and medical specialists, in order to characterize the properties of geological processes and agents, the dispersal of geological material and their effects on human population." [ 8 ] IMGA was founded in 2006 and manages affairs and funds, plans conferences, elections and publications, and they are also a way of encouraging growth and recognition in the field. [ 8 ] Although it was founded in 2006, it was a work in progress for ten years when a working group of medical geology was established by the International Union of Geological Sciences (IUGS) in 1996. [ 9 ] The goal of the working group was to advertise and make people aware of the harmful effects the environment has on our health. [ 9 ] | https://en.wikipedia.org/wiki/Medical_geology |
Medical gowns are hospital gowns worn by medical professionals as personal protective equipment (PPE) in order to provide a barrier between patient and professional. Whereas patient gowns are flimsy often with exposed backs and arms, PPE gowns, as seen below in the cardiac surgeon photograph, cover most of the exposed skin surfaces of the professional medics.
In several countries, PPE gowns for use in the COVID-19 pandemic became in appearance more like cleanroom suits as knowledge of the best practices filtered up through the national bureaucracies. For example, the European norm-setting bodies CEN and CENELEC on 30 March 2020 in collaboration with the European Commissioner for the Internal Market made freely-available the relevant standards documents in order "to tackle the severe shortage of protective masks, gloves and other products currently faced by many European countries. Providing free access to the standards will facilitate the work of the many companies wishing to reconvert their production lines in order to manufacture the equipment that is so urgently needed." [ 2 ]
The concept of PPE in regards to medical professionals was seen as early as the 17th century Plague doctor's outfit .
During the Ebola crisis of 2014, the WHO published a rapid advice guideline on PPE coveralls. [ 3 ]
The different levels of various gown types are categorized as follows: [ 4 ]
In the United States, medical gowns are medical devices regulated by the Food and Drug Administration . FDA divides medical gowns into three categories. A surgical gown is intended to be worn by health care personnel during surgical procedures. Surgical isolation gowns are used when there is a medium to high risk of contamination and a need for larger critical zones of protection. Non-surgical gowns are worn in low or minimal risk situations. [ 5 ]
Surgical and surgical isolation gowns are regulated by the FDA as a Class II medical device that require a 510(k) premarket notification , but non-surgical gowns are Class I devices exempt from premarket review. Surgical gowns only require protection of the front of the body due to the controlled nature of surgical procedures, while surgical isolation gowns and non-surgical gowns require protection over nearly the entire gown. [ 5 ]
In 2004, the FDA recognized ANSI / AAMI PB70:2003 standard on protective apparel and drapes for use in health care facilities. Surgical gowns must also conform to the ASTM F2407 standard for tear resistance, seam strength, lint generation, evaporative resistance, and water vapor transmission. Because surgical gowns are considered to be a surface-contacting device with intact skin, FDA recommends that cytotoxicity, sensitization, and irritation or intracutaneous reactivity is evaluated. [ 5 ]
The First Affiliated Hospital of the Zhejiang University School of Medicine in Hangzhou , Zhejiang Province , People's Republic of China developed their own protocol and equipment during the early months of the COVID-19 pandemic . A screenshot of the cover of the Handbook of COVID-19 Prevention and Treatment shows a picture of two rows of medical personnel, each wearing PPE gowns and PPE masks and PPE hoods and PPE goggles.
During the COVID-19 pandemic in Wuhan , doctors were provided with full PPE gown suits as early as January 2020.
During the COVID-19 pandemic , the European Commissioner for the Internal Market on 30 March 2020 listed the applicable norms for to help manufacturers re-convert their production lines: [ 2 ]
As seen in the accompanying gallery figure, at least one Israeli hospital had access to full Tyvek PPE gowns as early as 17 March 2020 during the COVID-19 pandemic .
In an early April article, 20 doctors from the whole of Italy describe their experience with coronavirus patient care. Their conclusion reads: [ 6 ]
Instituting precise well-established plans to perform undeferrable surgical procedures and emergencies on COVID-19-positive patient is mandatory. Hospitals must prepare specific internal protocols and arrange adequate training of the involved personnel.
Their findings are set out in a table entitled "Necessary personal protection equipment":
In a May 2017 research article, several French scientists complained that there was little harmonization across Europe for the names of pathogens , and went on to describe the PPE norms and regulations in France for infectious diseases under BSL-3 . [ 7 ] | https://en.wikipedia.org/wiki/Medical_gown |
The Medical Intelligence and Language Engineering Laboratory , also known as the MILE lab , is a research laboratory at the Indian Institute of Science , Bangalore under the Department of Electrical Engineering. The lab is known for its work on Image processing , online handwriting recognition , Text-To-Speech and Optical character recognition [ 1 ] systems, all of which are focused mainly on documents and speech in Indian languages . [ 2 ] The lab is headed by A. G. Ramakrishnan . [ 3 ]
One of the commitments of the MILE lab is the development of technology for people with visual impairment to harness knowledge from any available printed material in Indian languages. [ 4 ] The lab is working towards reaching this goal. Its work so far has included: document mosaicing of coloured, camera captured images ; text extraction from complex colour images, including camera captured images; document layout analysis ; detection of broken and merged characters; OCR technology for Tamil and Kannada; [ 5 ] text to speech conversion in Tamil and Kannada ; [ 6 ] pitch modification using discrete cosine transform in the source domain; [ 7 ] automated part of speech tagging; phrase prediction and prosody modeling.
Mozhi Vallan, the Tamil OCR [ 8 ] product developed by MILE Lab, is being used by Worth Trust and Karna Vidya Technology Centre, Chennai [ 9 ] for the conversion of printed school and college books to Braille format. Sri Ramakrishna Math, Chennai [ 10 ] is using it to convert their printed philosophical books in Tamil to computer readable text. Lipi Gnani, the Kannada OCR developed by MILE Lab is being used by Braille Transcription Centers of Mitrajyothi [ 11 ] and Canara Bank Relief & Welfare Society, [ 12 ] Bangalore for similar purposes. Also, Thirukkural, [ 13 ] the Tamil TTS system [ 14 ] developed by MILE Lab is being used by some school teachers in Singapore for assignments. Madhura, the Kannada TTS [ 15 ] developed by the lab, is being used by two blind students, integrated with a screen reader , to read aloud text OCR'ed with Lipi Gnani from Kannada books. Currently, the lab is researching on machine listening [ 16 ] and a novel temporal feature named as plosion index has been proposed, which has been shown to be extremely effective in detecting closure-burst transitions of stop consonants and affricates from continuous speech, even in noise . [ 17 ] Another feature proposed is DCTILPR, [ 18 ] which is a voice source based feature vector that improves the recognition performance of a speaker identification system.
In the early days, significant work was carried out in medical signal and image processing. A unique algorithm was proposed for ECG compression by treating each cardiac cycle as a vector, and applying linear prediction on the discrete wavelet transform of this vector, after normalizing its period using multirate processing based interpolation . [ 19 ] The maturity of the fetal lung was predicted using image texture features obtained from the liver and lung regions of the ultrasound images obtained from pregnant women [ 20 ] An effective technique was proposed for lossless compression of 3D magnetic resonance images of the brain . Each MRI slice was represented by uniform or adaptive mesh; affine transformation was applied between the corresponding mesh elements of adjacent slices and context-based entropy coding , on the residues. [ 21 ] | https://en.wikipedia.org/wiki/Medical_intelligence_and_language_engineering_lab |
A medical laboratory or clinical laboratory is a laboratory where tests are conducted out on clinical specimens to obtain information about the health of a patient to aid in diagnosis, treatment, and prevention of disease. [ 1 ] Clinical medical laboratories are an example of applied science , as opposed to research laboratories that focus on basic science , such as found in some academic institutions.
Medical laboratories vary in size and complexity and so offer a variety of testing services. More comprehensive services can be found in acute-care hospitals and medical centers, where 70% of clinical decisions are based on laboratory testing. [ 2 ] Doctors offices and clinics, as well as skilled nursing and long-term care facilities , may have laboratories that provide more basic testing services. Commercial medical laboratories operate as independent businesses and provide testing that is otherwise not provided in other settings due to low test volume or complexity. [ 3 ]
In hospitals and other patient-care settings, laboratory medicine is provided by the Department of Pathology and Medical Laboratory, and generally divided into two sections, each of which will be subdivided into multiple specialty areas. [ 4 ] The two sections are:
Layouts of clinical laboratories in health institutions vary greatly from one facility to another. For instance, some health facilities have a single laboratory for the microbiology section, while others have a separate lab for each specialty area.
The following is an example of a typical breakdown of the responsibilities of each area:
The staff of clinical laboratories may include:
The United States has a documented shortage of working laboratory professionals. For example, as of 2016 [update] vacancy rates for Medical Laboratory Scientists ranged from 5% to 9% for various departments. The decline is primarily due to retirements, and to at-capacity educational programs that cannot expand which limits the number of new graduates. Professional organizations and some state educational systems are responding by developing ways to promote the lab professions in an effort to combat this shortage. In addition, the vacancy rates for the MLS were tested again in 2018. The percentage range for the various departments has developed a broader range of 4% to as high as 13%. [ 13 ] The higher numbers were seen in the Phlebotomy and Immunology . [ 13 ] Microbiology was another department that has had a struggle with vacancies. [ 13 ] Their average in the 2018 survey was around 10-11% vacancy rate across the United States. [ 13 ] Recruitment campaigns, funding for college programs, and better salaries for the laboratory workers are a few ways they are focusing to decrease the vacancy rate. [ 14 ] The National Center For Workforce Analysis has estimated that by 2025 there will be a 24% increase in demand for lab professionals. [ 15 ] [ 16 ] Highlighted by the COVID-19 pandemic , work is being done to address this shortage including bringing pathology and laboratory medicine into the conversation surrounding access to healthcare. [ 17 ] COVID-19 brought the laboratory to the attention of the government and the media, thus giving opportunity for the staffing shortages as well as the resource challenges to be heard and dealt with. [ 18 ]
In most developed countries, there are two main types of lab processing the majority of medical specimens. Hospital laboratories are attached to a hospital , and perform tests on their patients. Private (or community ) laboratories receive samples from general practitioners , insurance companies, clinical research sites and other health clinics for analysis. For extremely specialised tests, samples may go to a research laboratory. Some tests involve specimens sent between different labs for uncommon tests. For example, in some cases it may be more cost effective if a particular laboratory specializes in a less common tests, receiving specimens (and payment) from other labs, while sending other specimens to other labs for those tests they do not perform.
In many countries there are specialized types of medical laboratories according to the types of investigations carried out. Organisations that provide blood products for transfusion to hospitals, such as the Red Cross, will provide access to their reference laboratory for their customers. Some laboratories specialize in Molecular diagnostic and cytogenetic testing, in order to provide information regarding diagnosis and treatment of genetic or cancer-related disorders.
In a hospital setting, sample processing will usually start with a set of samples arriving with a test request, either on a form or electronically via the laboratory information system ( LIS ). Inpatient specimens will already be labeled with patient and testing information provided by the LIS. Entry of test requests onto the LIS system involves typing (or scanning where barcodes are used) in the laboratory number, and entering the patient identification, as well as any tests requested. This allows laboratory analyzers, computers and staff to recognize what tests are pending, and also gives a location (such as a hospital department, doctor or other customer) for results reporting.
Once the specimens are assigned a laboratory number by the LIS, a sticker is typically printed that can be placed on the tubes or specimen containers. This label has a barcode that can be scanned by automated analyzers and test requests uploaded to the analyzer from the LIS.
Specimens are prepared for analysis in various ways. For example, chemistry samples are usually centrifuged and the serum or plasma is separated and tested. If the specimen needs to go on more than one analyzer, it can be divided into separate tubes.
Many specimens end up in one or more sophisticated automated analysers , that process a fraction of the sample to return one or more test results. Some laboratories use robotic sample handlers ( Laboratory automation ) to optimize the workflow and reduce the risk of contamination from sample handling by the staff.
The work flow in a hospital laboratory is usually heaviest from 2:00 am to 10:00 am. Nurses and doctors generally have their patients tested at least once a day with common tests such as complete blood counts and chemistry profiles. These orders are typically drawn during a morning run by phlebotomists for results to be available in the patient's charts for the attending physicians to consult during their morning rounds. Another busy time for the lab is after 3:00 pm when private practice physician offices are closing. Couriers will pick up specimens that have been drawn throughout the day and deliver them to the lab. Also, couriers will stop at outpatient drawing centers and pick up specimens. These specimens will be processed in the evening and overnight to ensure results will be available the following day.
The large amount of information processed in laboratories is managed by a system of software programs, computers, and terminology standards that exchange data about patients, test requests, and test results known as a Laboratory information system or LIS. The LIS is often interfaced with the hospital information system , EHR and/or laboratory instruments. Formats for terminologies for test processing and reporting are being standardized with systems such as Logical Observation Identifiers Names and Codes (LOINC) and Nomenclature for Properties and Units terminology (NPU terminology).
These systems enable hospitals and labs to order the correct test requests for each patient, keep track of individual patient and specimen histories, and help guarantee a better quality of results. Results are made available to care providers electronically or by printed hard copies for patient charts.
According to various regulations, such as the international ISO 15189 norm, all pathological laboratory results must be verified by a competent professional. In some countries, staffs composed of clinical scientists do the majority of this work inside the laboratory with certain abnormal results referred to the relevant pathologist . Doctor Clinical Laboratory scientists have the responsibility for limited interpretation of testing results in their discipline in many countries. Interpretation of results can be assisted by some software in order to validate normal or non-modified results.
In other testing areas, only professional medical staff ( pathologist or clinical Laboratory ) is involved with interpretation and consulting. Medical staff are sometimes also required in order to explain pathology results to physicians . For a simple result given by phone or to explain a technical problem, often a medical technologist or medical lab scientist can provide additional information.
Medical laboratory departments in some countries are exclusively directed by a specialized Doctor laboratory Science. In others, a consultant, medical or non-medical, may be the head the department. In Europe and some other countries, Clinical Scientists with a Masters level education may be qualified to head the department. Others may have a PhD and can have an exit qualification equivalent to medical staff (e.g., FRCPath in the UK).
In France, only medical staff ( Pharm.D. and M.D. specialized in anatomical pathology or clinical Laboratory Science ) are authorized to discuss laboratory results.
Credibility of medical laboratories is paramount to the health and safety of the patients relying on the testing services provided by these labs. Credentialing agencies vary by country. The international standard in use today for the accreditation of medical laboratories is ISO 15189 - Medical laboratories - Requirements for quality and competence.
In the United States, billions of dollars is spent on unaccredited lab tests, such as Laboratory developed tests which do not require accreditation or FDA approval; about a billion USD a year is spent on US autoimmune LDTs alone. [ 19 ] Accreditation is performed by the Joint Commission , College of American Pathologists , AAB (American Association of Bioanalysts), and other state and federal agencies. Legislative guidelines are provided under CLIA 88 ( Clinical Laboratory Improvement Amendments ) which regulates Medical Laboratory testing and personnel.
The accrediting body in Australia is NATA, where all laboratories must be NATA accredited to receive payment from Medicare.
In France the accrediting body is the Comité français d'accréditation (COFRAC). In 2010, modification of legislation established ISO 15189 accreditation as an obligation for all clinical laboratories. [ 20 ]
In the United Arab Emirates, the Dubai Accreditation Department ( DAC ) is the accreditation body that is internationally recognised [ 21 ] by the International Laboratory Accreditation Cooperation (ILAC) for many facilities and groups, including Medical Laboratories, Testing and Calibration Laboratories, and Inspection Bodies.
In Hong Kong, the accrediting body is Hong Kong Accreditation Service ( HKAS ). On 16 February 2004, HKAS launched its medical testing accreditation programme.
In Canada, laboratory accreditation is not mandatory, but is becoming more and more popular. Accreditation Canada ( AC ) is the national reference. Different provincial oversight bodies mandate laboratories in EQA participations like LSPQ (Quebec), IQMH (Ontario) for example.
The laboratory industry is a part of the broader healthcare and health technology industry. Companies exist at various levels, including clinical laboratory services , suppliers of instrumentation equipment and consumable materials, and suppliers and developers of diagnostic tests themselves (often by biotechnology companies). [ 22 ]
Clinical laboratory services includes large multinational corporations such LabCorp , Quest Diagnostics , and Sonic Healthcare [ 23 ] but a significant portion of revenue, estimated at 60% in the United States, is generated by hospital labs. [ 24 ] In 2018, the total global revenue for these companies was estimated to reach $146 billion by 2024. [ 25 ] Another estimate places the market size at $205 billion, reaching $333 billion by 2023. [ 26 ] The American Association for Clinical Chemistry (AACC) represents professionals in the field.
Clinical laboratories are supplied by other multinational companies which focus on materials and equipment, which can be used for both scientific research and medical testing. The largest of these is Thermo Fisher Scientific . [ 27 ] In 2016, global life sciences instrumentation sales were around $47 billion, not including consumables, software, and services. [ 27 ] In general, laboratory equipment includes lab centrifuges, transfection solutions, water purification systems, extraction techniques, gas generators, concentrators and evaporators, fume hoods, incubators, biological safety cabinets, bioreactors and fermenters, microwave-assisted chemistry, lab washers, and shakers and stirrers. [ 28 ]
In the United States, estimated total revenue as of 2016 was $75 billion, about 2% of total healthcare spending . [ 23 ] In 2016, an estimated 60% of revenue was done by hospital labs, with 25% done by two independent companies (LabCorp and Quest). [ 24 ] Hospital labs may also outsource their lab, known as outreach, to run tests; however, health insurers may pay the hospitals more than they would pay a laboratory company for the same test, but as of 2016, the markups were questioned by insurers. [ 29 ] Rural hospitals, in particular, can bill for lab outreach under the Medicare's 70/30 shell rule. [ 30 ]
Laboratory developed tests are designed and developed inside a specific laboratory and do not require FDA approval; due to technological innovations, they have become more common [ 31 ] and are estimated at a total value of $11 billion in 2016. [ 32 ]
Due to the rise of high-deductible health plans , laboratories have sometimes struggled to collect when billing patients; consequently, some laboratories have shifted to become more "consumer-focused". [ 33 ] | https://en.wikipedia.org/wiki/Medical_laboratory |
A medical oddity is an unusual predicament or event which takes place in a medical context. Some examples of medical oddities might include: "lost and found" surgical instruments (in the body), grotesquely oversized tumors , (human) male pregnancy , rare or " orphan " illnesses, rare allergies (such as to water ), strange births (extra or missing organs), and bizarre syndromes (such as Capgras delusion ).
Medical oddities can also include unusual discoveries in purchased food , such as finding a severed finger or thumb in a hamburger.
Medical oddities are also known as medical curiosities . While not strictly paranormal , they are classically Fortean .
This medical article is a stub . You can help Wikipedia by expanding it . | https://en.wikipedia.org/wiki/Medical_oddity |
Medical physics [ 1 ] deals with the application of the concepts and methods of physics to the prevention, diagnosis and treatment of human diseases with a specific goal of improving human health and well-being. [ 2 ] Since 2008, medical physics has been included as a health profession according to International Standard Classification of Occupation of the International Labour Organization . [ 3 ]
Although medical physics may sometimes also be referred to as biomedical physics , medical biophysics , applied physics in medicine , physics applications in medical science , radiological physics or hospital radio-physics , a " medical physicist " is specifically a health professional [ 4 ] with specialist education and training in the concepts and techniques of applying physics in medicine and competent to practice independently in one or more of the subfields of medical physics. [ 5 ] Traditionally, medical physicists are found in the following healthcare specialties: radiation oncology (also known as radiotherapy or radiation therapy), diagnostic and interventional radiology (also known as medical imaging), nuclear medicine , and radiation protection . Medical physics of radiation therapy can involve work such as dosimetry , linac quality assurance, and brachytherapy . Medical physics of diagnostic and interventional radiology involves medical imaging techniques such as magnetic resonance imaging , ultrasound , computed tomography and x-ray . Nuclear medicine will include positron emission tomography and radionuclide therapy. However one can find Medical Physicists in many other areas such as physiological monitoring, audiology, neurology, neurophysiology, cardiology and others.
Medical physics departments may be found in institutions such as universities, hospitals, and laboratories. University departments are of two types. The first type are mainly concerned with preparing students for a career as a hospital Medical Physicist and research focuses on improving the practice of the profession. A second type (increasingly called 'biomedical physics') has a much wider scope and may include research in any applications of physics to medicine from the study of biomolecular structure to microscopy and nanomedicine.
In hospital medical physics departments, the mission statement for medical physicists as adopted by the European Federation of Organisations for Medical Physics (EFOMP) is the following: [ 6 ] [ 7 ]
Medical Physicists will contribute to maintaining and improving the quality, safety and cost-effectiveness of healthcare services through patient-oriented activities requiring expert action, involvement or advice regarding the specification, selection, acceptance testing, commissioning, quality assurance/control and optimised clinical use of medical devices and regarding patient risks and protection from associated physical agents (e.g., x-rays, electromagnetic fields, laser light, radionuclides) including the prevention of unintended or accidental exposures; all activities will be based on current best evidence or own scientific research when the available evidence is not sufficient. The scope includes risks to volunteers in biomedical research, carers and comforters. The scope often includes risks to workers and public particularly when these impact patient risk
The term "physical agents" refers to ionising and non-ionising electromagnetic radiations , static electric and magnetic fields , ultrasound , laser light and any other Physical Agent associated with medical e.g., x-rays in computerised tomography (CT), gamma rays /radionuclides in nuclear medicine, magnetic fields and radio-frequencies in magnetic resonance imaging (MRI), ultrasound in ultrasound imaging and Doppler measurements.
This mission includes the following 11 key activities:
Some education institutions house departments or programs bearing the title "medical biophysics" or "biomedical physics" or "applied physics in medicine". Generally, these fall into one of two categories: interdisciplinary departments that house biophysics , radiobiology , and medical physics under a single umbrella; [ 8 ] [ 9 ] [ 10 ] and undergraduate programs that prepare students for further study in medical physics, biophysics, or medicine. [ 11 ] [ 12 ] Most of the scientific concepts in bionanotechnology are derived from other fields. Biochemical principles that are used to understand the material properties of biological systems are central in bionanotechnology because those same principles are to be used to create new technologies. [ citation needed ] Material properties and applications studied in bionanoscience include mechanical properties (e.g. deformation, adhesion, failure), electrical/electronic (e.g. electromechanical stimulation, capacitors , energy storage/batteries), optical (e.g. absorption, luminescence , photochemistry ), thermal (e.g. thermomutability, thermal management), biological (e.g. how cells interact with nanomaterials, molecular flaws/defects, biosensing, biological mechanisms such as mechanosensation ), nanoscience of disease (e.g. genetic disease, cancer, organ/tissue failure), as well as computing (e.g. DNA computing ) and agriculture (target delivery of pesticides, hormones and fertilizers. [ 13 ] [ 14 ] [ 15 ] [ 16 ]
The International Organization for Medical Physics (IOMP) recognizes main areas of medical physics employment and focus. [ 17 ] [ 18 ]
Medical imaging physics is also known as diagnostic and interventional radiology physics.
Clinical (both "in-house" and "consulting") physicists [ 19 ] typically deal with areas of testing, optimization, and quality assurance of diagnostic radiology physics areas such as radiographic X-rays , fluoroscopy , mammography , angiography , and computed tomography , as well as non-ionizing radiation modalities such as ultrasound , and MRI . They may also be engaged with radiation protection issues such as dosimetry (for staff and patients). In addition, many imaging physicists are often also involved with nuclear medicine systems, including single photon emission computed tomography (SPECT) and positron emission tomography (PET).
Sometimes, imaging physicists may be engaged in clinical areas, but for research and teaching purposes, [ 20 ] such as quantifying intravascular ultrasound as a possible method of imaging a particular vascular object.
Radiation therapeutic physics is also known as radiotherapy physics or radiation oncologist physics.
The majority of medical physicists currently working in the US, Canada, and some western countries are of this group. A radiation therapy physicist typically deals with linear accelerator (Linac) systems and kilovoltage x-ray treatment units on a daily basis, as well as other modalities such as TomoTherapy , gamma knife , Cyberknife , proton therapy , and brachytherapy . [ 21 ] [ 22 ] [ 23 ] The academic and research side of therapeutic physics may encompass fields such as boron neutron capture therapy , sealed source radiotherapy , terahertz radiation , high-intensity focused ultrasound (including lithotripsy ), optical radiation lasers , ultraviolet etc. including photodynamic therapy , as well as nuclear medicine including unsealed source radiotherapy , and photomedicine , which is the use of light to treat and diagnose disease.
Nuclear medicine is a branch of medicine that uses radiation to provide information about the functioning of a person's specific organs or to treat disease. The thyroid , bones , heart , liver and many other organs can be easily imaged, and disorders in their function revealed. In some cases radiation sources can be used to treat diseased organs, or tumours. Five Nobel laureates have been intimately involved with the use of radioactive tracers in medicine.
Over 10,000 hospitals worldwide use radioisotopes in medicine, and about 90% of the procedures are for diagnosis. The most common radioisotope used in diagnosis is technetium-99m , with some 30 million procedures per year, accounting for 80% of all nuclear medicine procedures worldwide. [ 24 ]
Health physics is also known as radiation safety or radiation protection . Health physics is the applied physics of radiation protection for health and health care purposes. It is the science concerned with the recognition, evaluation, and control of health hazards to permit the safe use and application of ionizing radiation. Health physics professionals promote excellence in the science and practice of radiation protection and safety.
Some aspects of non-ionizing radiation physics may be considered under radiation protection or diagnostic imaging physics. Imaging modalities include MRI , optical imaging and ultrasound . Safety considerations include these areas and lasers
Physiological measurements have also been used to monitor and measure various physiological parameters. Many physiological measurement techniques are non-invasive and can be used in conjunction with, or as an alternative to, other invasive methods. Measurement methods include electrocardiography Many of these areas may be covered by other specialities, for example medical engineering or vascular science. [ 25 ]
Other closely related fields to medical physics include fields which deal with medical data, information technology and computer science for medicine.
Non-clinical physicists may or may not focus on the above areas from an academic and research point of view, but their scope of specialization may also encompass lasers and ultraviolet systems (such as photodynamic therapy ), fMRI and other methods for functional imaging as well as molecular imaging , electrical impedance tomography , diffuse optical imaging , optical coherence tomography , and dual energy X-ray absorptiometry . | https://en.wikipedia.org/wiki/Medical_physics |
A prescription , often abbreviated ℞ or Rx , is a formal communication from physicians or other registered healthcare professionals to a pharmacist , authorizing them to dispense a specific prescription drug for a specific patient. Historically, it was a physician's instruction to an apothecary listing the materials to be compounded into a treatment—the symbol ℞ (a capital letter R, crossed to indicate abbreviation) comes from the first word of a medieval prescription, Latin recipe ( lit. ' take thou ' ), that gave the list of the materials to be compounded.
The symbol "℞", sometimes transliterated as "R x " or "Rx", is recorded in 16th century manuscripts as an abbreviation of the late Latin instruction recipe , meaning 'receive'. [ 1 ] [ a ] Originally abbreviated Rc , the later convention of using a slash to indicate abbreviation resulted in an R with a straight stroke through its right "leg". [ 1 ] [ b ] [ c ] Medieval prescriptions invariably began with the instruction from the physician to the apothecary to "take" certain materials and compound them in specified ways. [ 6 ]
For a communication to be accepted as a legal medical prescription, it needs to be filed by a qualified dentist, advanced practice nurse, physician, or veterinarian, for whom the medication prescribed is within their scope of practice to prescribe. [ citation needed ] This is regardless of whether the prescription includes prescription drugs , controlled substances , or over-the-counter treatments. [ citation needed ]
Prescriptions may be entered into an electronic medical record system and transmitted electronically to a pharmacy. Alternatively, a prescription may be handwritten on preprinted prescription forms that have been assembled into pads, or printed onto similar forms using a computer printer or even on plain paper, according to the circumstances. In some cases, a prescription may be transmitted orally by telephone from the physician to the pharmacist. The content of a prescription includes the name and address of the prescribing provider and any other legal requirements, such as a registration number (e.g., a DEA number in the United States). Unique to each prescription is the name of the patient. In the United Kingdom and Ireland, the patient's name and address must also be recorded. Each prescription is dated, and some jurisdictions may place a time limit on the prescription. [ 7 ] In the past, prescriptions contained instructions for the pharmacist to use for compounding the pharmaceutical product, but most prescriptions now specify pharmaceutical products that were manufactured and require little or no preparation by the pharmacist. [ citation needed ] Prescriptions also contain directions for the patient to follow when taking the drug. These directions are printed on the label of the pharmaceutical product.
The word prescription , from pre- ('before') and script ('writing, written'), refers to the fact that the prescription is an order that must be written down before a drug can be dispensed. Those within the industry will often call prescriptions simply "scripts".
Every prescription contains who prescribed the prescription , who the prescription is valid for , and what is prescribed . Some jurisdictions, drug types or patient groups require additional information as explained below.
Many brand name drugs have cheaper generic drug substitutes that are therapeutically and biochemically equivalent. Prescriptions will also contain instructions on whether the prescriber will allow the pharmacist to substitute a generic version of the drug . This instruction is communicated in a number of ways. In some jurisdictions, the preprinted prescription contains two signature lines: one line has "dispense as written" printed underneath; the other line has "substitution permitted" underneath. Some have a preprinted box "dispense as written" for the prescriber to check off (but this is easily checked off by anyone with access to the prescription). In other jurisdictions, the protocol is for the prescriber to handwrite one of the following phrases: "dispense as written", "DAW", "brand necessary", "do not substitute", "no substitution", "medically necessary", "do not interchange". [ 8 ] In Britain's National Health Service , doctors are reminded that money spent on branded rather than generic drugs is consequently not available for more deserving cases . [ 9 ]
In some jurisdictions, it may be a legal requirement to include the age of child on the prescription. [ 10 ] For pediatric prescriptions some [ who? ] advise the inclusion of the age of the child if the patient is less than twelve and the age and months if less than five. (In general, including the age on the prescription is helpful.) Adding the weight of the child is also helpful.
Prescriptions in the US often have a "label" box. [ 11 ] When checked, the pharmacist is instructed to label the medication and provide information about the prescription itself is given in addition to instructions on taking the medication. Otherwise, the patient is simply given the instructions. Some prescribers further inform the patient and pharmacist by providing the indication for the medication; i.e. what is being treated. This assists the pharmacist in checking for errors as many common medications can be used for multiple medical conditions. Some prescriptions will specify whether and how many "repeats" or "refills" are allowed; that is whether the patient may obtain more of the same medication without getting a new prescription from the medical practitioner. Regulations may restrict some types of drugs from being refilled.
National or local (e.g. US state or Canadian provincial) legislation governs who can write a prescription. In the United States, physicians (either M.D. , D.O. or D.P.M. [ 12 ] ) have the broadest prescriptive authority. All 50 US states and the District of Columbia allow licensed certified Physician Assistants (PAs) prescription authority (with some states, limitations exist to controlled substances). All 50 US states and the District of Columbia, Puerto Rico and Guam allow registered certified nurse practitioners and other advanced practice registered nurses (such as certified nurse-midwives ) prescription power (with some states including limitations to controlled substances). [ 13 ] [ 14 ] Many other healthcare professions also have prescriptive authority related to their area of practice. Veterinarians and dentists have prescribing power in all 50 US states and the District of Columbia. Clinical pharmacists are allowed to prescribe in some US states through the use of a drug formulary or collaboration agreements. Florida pharmacists can write prescriptions for a limited set of drugs. [ 15 ] In all US states, optometrists prescribe medications to treat certain eye diseases, and also issue spectacle and contact lens prescriptions for corrective eyewear. [ 16 ] Several US states have passed RxP legislation, allowing clinical psychologists who are registered as medical psychologists and have also undergone specialized training in script-writing, to prescribe drugs to treat emotional and mental disorders.
In August 2013, legislative changes in the UK allowed physiotherapists and podiatrists to have independent prescribing rights for licensed medicines that are used to treat conditions within their own area of expertise and competence. In 2018 this was extended to paramedics . [ 17 ] [ 18 ]
Some jurisdictions [ 19 ] [ 20 ] allow certain physicians (sometimes a government official like the state Secretary of Health, [ 21 ] sometimes physicians in local clinics or pharmacies [ 22 ] ) to write "standing orders" that act like a prescription for everyone in the general public. These orders also provide a standard procedure for determining if administration is necessary and details of how it is to be performed safely. These are typically used to authorize certain people to perform preventive, low-risk, or emergency care that would be otherwise logistically cumbersome to authorize for individual patients, including vaccinations, [ 23 ] prevention of cavities , birth control, treatment of infectious diseases, [ 24 ] and reversal of drug overdoses. [ 21 ]
Doctors' handwriting is a reference to the stereotypically illegible handwriting of some medical practitioners , which sometimes causes errors in dispensing. In the US, illegible handwriting has been indirectly responsible for at least 7,000 deaths annually. [ 25 ] [ 26 ] [ 27 ] [ 28 ]
Some jurisdictions have legislatively required prescriptions to be legible— Florida specifies "legibly printed or typed" [ 29 ] —and the Institute for Safe Medication Practices advocated the elimination of handwritten prescriptions altogether. [ 30 ] There have been numerous devices designed to electronically read the handwriting of doctors, including electronic character recognition , [ 31 ] keyword spotters , [ 32 ] and " postprocessing approaches", [ 33 ] though the gradual shift to electronic health records and electronic prescriptions may alleviate the need for handwritten prescriptions altogether. [ 34 ] In Britain's NHS, remaining paper prescriptions are almost invariably computer printed, and electronic (rather than paper) communication between surgery and pharmacy is increasingly the norm. [ 35 ]
Over the years, prescribers have developed many conventions for prescription-writing, with the goal of avoiding ambiguities or misinterpretation. [ 36 ] [ 37 ] [ 38 ] These include:
Many abbreviations are derived from Latin phrases. Hospital pharmacies have more abbreviations, some specific to the hospital. Different jurisdictions follow different conventions on what is abbreviated or not. Prescriptions that do not follow area conventions may be flagged as possible forgeries.
Some abbreviations that are ambiguous, or that in their written form might be confused with something else, are not recommended and should be avoided. These are flagged in the table in the main article . However, all abbreviations carry an increased risk for confusion and misinterpretation and should be used cautiously.
Over-the-counter medications and non-controlled medical supplies such as dressings , which do not require a prescription, may also be prescribed. Depending upon a jurisdiction 's medical system, non-prescription drugs may be prescribed because drug benefit plans may reimburse the patient only if the over-the-counter medication is taken at the direction of a qualified medical practitioner . In the countries of the UK, National Health Service (NHS) prescriptions are either free or have a fixed price per item; [ 39 ] a prescription may be issued so the patient does not have to purchase the item at commercial price.
Some medical software requires a prescription. [ 40 ]
Legislation may define certain equipment as "prescription devices". [ 41 ] Such prescription devices can only be used under the supervision of authorized personnel and such authorization is typically documented using a prescription. Examples of prescription devices include dental cement (for affixing braces to tooth surfaces), various prostheses, gut sutures, sickle cell tests, cervical cap and ultrasound monitor. [ citation needed ]
In some jurisdictions, hypodermic syringes are in a special class of their own, regulated as illicit drug use accessories [ 42 ] separate from regular medical legislation. Such legislation often allows syringes to be dispensed only with a prescription. [ citation needed ]
The idea of prescriptions dates back to the beginning of history. So long as there were medications and a writing system to capture directions for preparation and usage, there were prescriptions. The oldest known medical prescription text was found at Ebla , in modern Syria , and dates back to around 2500 BCE. [ 43 ] [ 44 ] [ 45 ]
Modern prescriptions are actually extemporaneous prescriptions (from the Latin ex tempore , 'at/from the time'), [ 46 ] meaning that the prescription is written on the spot for a specific patient with a specific ailment. This is distinguished from a non-extemporaneous prescription that is a generic recipe for a general ailment. Modern prescriptions evolved with the separation of the role of the pharmacists from that of the physician. [ 47 ] Today the term extemporaneous prescriptions is reserved for compound prescriptions that requires the pharmacist to mix or compound the medication in the pharmacy for the specific needs of the patient. [ citation needed ]
Predating modern legal definitions of a prescription, a prescription traditionally is composed of four parts: a superscription , inscription , subscription , and signature . [ 48 ]
The superscription section contains the date of the prescription and patient information (name, address, age, etc.). The symbol "℞" separates the superscription from the inscriptions sections. In this arrangement of the prescription, the "℞" is a symbol for recipe or literally the imperative "take!" This is an exhortation to the pharmacist by the medical practitioner, "I want the patient to have the following medication" [ 49 ] – in other words, "take the following components and compound this medication for the patient".
The inscription section defines what is the medication. The inscription section is further composed of one or more of: [ 50 ]
The subscription section contains dispensing directions to the pharmacist. This may be compounding instructions or quantities.
The signature section contains directions to the patient [ 51 ] and is often abbreviated "Sig." [ 52 ] or "Signa." [ 53 ] It also obviously contains the signature of the prescribing medical practitioner though the word signature has two distinct meanings here and the abbreviations are sometimes used to avoid confusion.
Thus sample prescriptions in modern textbooks are often presented as:
As a prescription is nothing more than information among a prescriber, pharmacist and patient , information technology can be applied to it. Existing information technology is adequate to print out prescriptions. Hospital information systems in some hospitals do away with prescriptions within the hospital. There are proposals to securely transmit the prescription from the prescriber to the pharmacist using smartcard or the internet. [ 54 ] In the UK a project called the Electronic Transfer of Prescriptions (ETP) within the National Programme for IT (NPfIT) is currently [ when? ] piloting such a scheme between prescribers and pharmacies.
Within computerized pharmacies, the information on paper prescriptions is recorded into a database. Afterwards, the paper prescription is archived for storage and legal reasons.
A pharmacy chain is often linked together through corporate headquarters with computer networking . A person who has a prescription filled at one branch can get a refill of that prescription at any other store in the chain, as well as have their information available for new prescriptions at any branch.
Some online pharmacies also offer services to customers over the internet, allowing users to specify the store that they will pick up the medicine from.
Many pharmacies now offer services to ship prescription refills right to the patient's home. They also offer mail service where you can mail in a new, original prescription and a signed document, and they will ship the filled prescription back to you.
Pharmacy information systems are a potential source of valuable information for pharmaceutical companies as it contains information about the prescriber's prescribing habits. Prescription data mining of such data is a developing, specialized field. [ 55 ]
Many prescribers lack the digitized information systems that reduce prescribing errors. [ 56 ] To reduce these errors, some investigators have developed modified prescription forms that prompt the prescriber to provide all the desired elements of a good prescription. The modified forms also contain predefined choices such as common quantities, units and frequencies that the prescriber may circle rather than write out. Such forms are thought to reduce errors, especially omission and handwriting errors and are actively under evaluation. [ 57 ] | https://en.wikipedia.org/wiki/Medical_prescription |
Medical technology assessment (MTA) is the objective evaluation of a medical technology regarding its safety and performance, its (future) impact on clinical and non-clinical patient outcomes as well as its interactive effects on economical, organizational, social, juridical and ethical aspects of healthcare. Medical technologies are assessed both in absolute terms and in comparison to other (combinations of) medical technologies, procedures, treatments or ‘doing-nothing’.
The aim of MTA is to provide objective, high-quality information that relevant stakeholders use for decision-making about for example development, pricing, market access and reimbursement of new medical technologies. As such, MTA is similar to health technology assessment (HTA), except that HTA has a wider scope and may include assessments of for example organizational or financial interventions.
The classical approach of MTA is to evaluate technologies after they enter the marketplace. Yet, a growing number of researchers and policy-makers argue that new technologies should be evaluated before they diffuse into routine clinical practice. [ 1 ] MTA of biomedical innovations in a very early stage of development could improve health outcomes, minimise wrong investment and prevent social and ethical conflicts. [ 2 ]
One particular method within the area of early MTA is constructive technology assessment (CTA). CTA is particularly appropriate for the early assessment of dynamic technologies that are implemented under uncertain circumstances. CTA is based on the idea that during the course of technology development, choices are constantly being made about the form, the function, and the use of that technology. Especially in early stages, technologies are not always stable, nor are its specifications and neither is its use, as both technology and environment will mutually influence each other. In recent years, CTA has developed from assessing the (clinical) impact of a new technology to a much broader approach, including the analysis of design, development, and implementation of that new technology. [ 3 ]
In the Netherlands, the department Health Technology and Services Research (HTSR) of the University of Twente and the institute for Medical Technology Assessment (iMTA) of the Erasmus University Rotterdam perform early MTA and CTA in collaboration with technology users (patients, healthcare professionals), technology developers (academic and industrial), technology investors (venture capitalists, government, etc.) technology procurers (hospitals, patients, etc.) and decision-makers in healthcare (patients, policy-makers etc.) By performing excellent scientific research, that is valuable and relevant for society, HTSR and iMTA aim to support decisions about early development and implementation of health care technology in order to achieve high quality healthcare for individual patients. Examples of the research of HTSR include the early economic evaluation of neuromuscular electrical stimulation in the treatment of shoulder pain and early phase technology assessment of nanotechnology in oncology. [ 4 ] [ 5 ] Examples of the work if iMTA include the development of the widely used cost-effectiveness acceptability curves (CEACs), [ 6 ] the introduction of the friction cost method, [ 7 ] the valuation if informal care with the CarerQoL instrument [ permanent dead link ] and the estimation of indirect medical costs . | https://en.wikipedia.org/wiki/Medical_technology_assessment |
A medical test is a medical procedure performed to detect , diagnose , or monitor diseases, disease processes, susceptibility, or to determine a course of treatment. Medical tests such as, physical and visual exams, diagnostic imaging , genetic testing, chemical and cellular analysis, relating to clinical chemistry and molecular diagnostics , are typically performed in a medical setting .
Medical tests can be classified by their purposes, including diagnosis, screening or monitoring.
A diagnostic test is a procedure performed to confirm or determine the presence of disease in an individual suspected of having a disease, usually following the report of symptoms, or based on other medical test results. [ 1 ] [ 2 ] This includes posthumous diagnosis . Examples of such tests are:
Screening refers to a medical test or series of tests used to detect or predict the presence of disease in at-risk individuals within a defined group such as a population, family, or workforce. [ 4 ] [ 5 ] Screenings may be performed to monitor disease prevalence, manage epidemiology, aid in prevention, or strictly for statistical purposes. [ 6 ]
Examples of screenings include measuring the level of TSH in the blood of a newborn infant as part of newborn screening for congenital hypothyroidism , [ 7 ] checking for Lung cancer in non-smoking individuals who are exposed to second-hand smoke in an unregulated working environment, and Pap smear screening for prevention or early detection of cervical cancer . [ citation needed ]
Some medical tests are used to monitor the progress of, or response to medical treatment .
Most test methods can be classified into one of the following broad groups:
In vitro tests can be classified according to the location of the sample being tested, including:
Tests performed in a physical examination are usually aimed at detecting a symptom or sign , and in these cases, a test that detects a symptom or sign is designated a positive test , and a test that indicated absence of a symptom or sign is designated a negative test, as further detailed in a separate section below.A quantification of a target substance, a cell type or another specific entity is a common output of, for example, most blood tests . This is not only answering if a target entity is present or absent, but also how much is present. In blood tests, the quantification is relatively well specified, such as given in mass concentration , while most other tests may be quantifications as well although less specified, such as a sign of being "very pale " rather than "slightly pale". Similarly, radiologic images are technically quantifications of radiologic opacity of tissues. [ citation needed ]
Especially in the taking of a medical history , there is no clear limit between a detecting or quantifying test versus rather descriptive information of an individual. For example, questions regarding the occupation or social life of an individual may be regarded as tests that can be regarded as positive or negative for the presence of various risk factors, or they may be regarded as "merely" descriptive, although the latter may be at least as clinically important. [ citation needed ]
The result of a test aimed at detection of an entity may be positive or negative : this has nothing to do with a bad prognosis , but rather means that the test worked or not, and a certain parameter that was evaluated was present or not. For example, a negative screening test for breast cancer means that no sign of breast cancer could be found (which is in fact very positive for the patient). [ citation needed ]
The classification of tests into either positive or negative results in a binary classification , allowing for the application of bayesian probability and the calculation of diagnostic test accuracy measures, such as sensitivity, specificity , likelihood ratios , and the diagnostic odds ratio . [ 14 ] [ 15 ] These metrics are commonly used in systematic review of diagnostic test accuracy and meta-analyses of diagnostic accuracy studies. [ 16 ]
Tests whose results are of continuous values, such as most blood values , can be interpreted as they are, or they can be converted to a binary ones by defining a cutoff value , with test results being designated as positive or negative depending on whether the resultant value is higher or lower than the cutoff.
In the finding of a pathognomonic sign or symptom it is almost certain that the target condition is present, and in the absence of finding a sine qua non sign or symptom it is almost certain that the target condition is absent. In reality, however, the subjective probability of the presence of a condition is never exactly 100% or 0%, so tests are rather aimed at estimating a post-test probability of a condition or other entity.
Most diagnostic tests basically use a reference group to establish performance data such as predictive values , likelihood ratios and relative risks , which are then used to interpret the post-test probability for an individual.
In monitoring tests of an individual, the test results from previous tests on that individual may be used as a reference to interpret subsequent tests.
Some medical testing procedures have associated health risks, and even require general anesthesia , such as the mediastinoscopy . [ 17 ] Other tests, such as the blood test or pap smear have little to no direct risks. [ 18 ] Medical tests may also have indirect risks , such as the stress of testing, and riskier tests may be required as follow-up for a (potentially) false positive test result. Consult the health care provider (including physicians , physician assistants , and nurse practitioners ) prescribing any test for further information.
Each test has its own indications and contraindications. An indication is a valid medical reason to perform the test. A contraindication is a valid medical reason not to perform the test. For example, a basic cholesterol test may be indicated (medically appropriate) for a middle-aged person. However, if the same test was performed on that person very recently, then the existence of the previous test is a contraindication for the test (a medically valid reason to not perform it).
Information bias is the cognitive bias that causes healthcare providers to order tests that produce information that they do not realistically expect or intend to use for the purpose of making a medical decision. Medical tests are indicated when the information they produce will be used. For example, a screening mammogram is not indicated (not medically appropriate) for a woman who is dying, because even if breast cancer is found, she will die before any cancer treatment could begin.
In a simplified fashion, how much a test is indicated for an individual depends largely on its net benefit for that individual. Tests are chosen when the expected benefit is greater than the expected harm. The net benefit may roughly be estimated by: [ 19 ]
b n = Δ p × r i × ( b i − h i ) − h t {\displaystyle b_{n}=\Delta p\times r_{i}\times (b_{i}-h_{i})-h_{t}}
, where:
Some additional factors that influence a decision whether a medical test should be performed or not included: cost of the test, availability of additional tests, potential interference with subsequent test (such as an abdominal palpation potentially inducing intestinal activity whose sounds interfere with a subsequent abdominal auscultation ), time taken for the test or other practical or administrative aspects. The possible benefits of a diagnostic test may also be weighed against the costs of unnecessary tests and resulting unnecessary follow-up and possibly even unnecessary treatment of incidental findings. [ 20 ]
In some cases, tests being performed are expected to have no benefit for the individual being tested. Instead, the results may be useful for the establishment of statistics in order to improve health care for other individuals. Patients may give informed consent to undergo medical tests that will benefit other people.
In addition to considerations of the nature of medical testing noted above, other realities can lead to misconceptions and unjustified expectations among patients. These include: Different labs have different normal reference ranges; slightly different values will result from repeating a test; "normal" is defined by a spectrum along a bell curve resulting from the testing of a population, not by "rational, science-based, physiological principles"; sometimes tests are used in the hope of turning something up to give the doctor a clue as to the nature of a given condition; and imaging tests are subject to fallible human interpretation and can show "incidentalomas" , most of which "are benign, will never cause symptoms, and do not require further evaluation," although clinicians are developing guidelines for deciding when to pursue diagnoses of incidentalomas. [ 21 ]
The QUADAS-2 revision is available. [ 22 ] | https://en.wikipedia.org/wiki/Medical_test |
Medical toxicology is a subspecialty of medicine focusing on toxicology and providing the diagnosis , management , and prevention of poisoning and other adverse effects due to medications , occupational and environmental toxicants, and biological agents. [ 1 ] Medical toxicologists are involved in the assessment and treatment of a wide variety of problems, including acute or chronic poisoning , adverse drug reactions (ADRs), drug overdoses , envenomations , substance abuse , industrial accidents , and other chemical exposures.
Medical toxicology is officially recognized as a medical subspecialty by the American Board of Medical Specialties . [ 1 ] Its practitioners are physicians , whose primary specialization is generally in emergency medicine , occupational medicine , or pediatrics .
Medical toxicology is closely related to clinical toxicology , with the latter discipline encompassing non-physicians as well (generally pharmacists or scientists ). | https://en.wikipedia.org/wiki/Medical_toxicology |
Medication (also called medicament , medicine , pharmaceutical drug , medicinal product , medicinal drug or simply drug ) is a drug used to diagnose , cure , treat, or prevent disease. [ 1 ] [ 2 ] Drug therapy ( pharmacotherapy ) is an important part of the medical field and relies on the science of pharmacology for continual advancement and on pharmacy for appropriate management.
Drugs are classified in many ways. One of the key divisions is by level of control , which distinguishes prescription drugs (those that a pharmacist dispenses only on the medical prescription ) from over-the-counter drugs (those that consumers can order for themselves). Medicines may be classified by mode of action, route of administration , biological system affected, or therapeutic effects . The World Health Organization keeps a list of essential medicines .
Drug discovery and drug development are complex and expensive endeavors undertaken by pharmaceutical companies , academic scientists, and governments. As a result of this complex path from discovery to commercialization, partnering has become a standard practice for advancing drug candidates through development pipelines. Governments generally regulate what drugs can be marketed, how drugs are marketed , and in some jurisdictions, drug pricing . Controversies have arisen over drug pricing and disposal of used medications.
Medication is a medicine or a chemical compound used to treat or cure illness. According to Encyclopædia Britannica , medication is "a substance used in treating a disease or relieving pain ". [ 3 ]
As defined by the National Cancer Institute , dosage forms of medication can include tablets , capsules , liquids, creams , and patches. Medications can be administered in different ways, such as by mouth , by infusion into a vein , or by drops put into the ear or eye . A medication that does not contain an active ingredient and is used in research studies is called a placebo . [ 4 ]
In Europe, the term is "medicinal product", and it is defined by EU law as:
In the US, a "drug" is:
Drug use among elderly Americans has been studied; in a group of 2,377 people with an average age of 71 surveyed between 2005 and 2006, 84% took at least one prescription drug, 44% took at least one over-the-counter (OTC) drug, and 52% took at least one dietary supplement ; in a group of 2245 elderly Americans (average age of 71) surveyed over the period 2010 – 2011, those percentages were 88%, 38%, and 64%. [ 7 ]
One of the key classifications is between traditional small molecule drugs; usually derived from chemical synthesis and biological medical products ; which include recombinant proteins , vaccines , blood products used therapeutically (such as IVIG ), gene therapy , and cell therapy (for instance, stem cell therapies). [ citation needed ]
Pharmaceuticals or drugs or medicines are classified into various other groups besides their origin on the basis of pharmacological properties like mode of action and their pharmacological action or activity, [ 8 ] such as by chemical properties , mode or route of administration , biological system affected, or therapeutic effects . An elaborate and widely used classification system is the Anatomical Therapeutic Chemical Classification System (ATC system). The World Health Organization keeps a list of essential medicines .
A sampling of classes of medicine includes:
Pharmaceuticals may also be described as "specialty", independent of other classifications, which is an ill-defined class of drugs that might be difficult to administer, require special handling during administration, require patient monitoring during and immediately after administration, have particular regulatory requirements restricting their use, and are generally expensive relative to other drugs. [ 9 ]
Drugs affecting the central nervous system include psychedelics , hypnotics , anaesthetics , antipsychotics , eugeroics , antidepressants (including tricyclic antidepressants , monoamine oxidase inhibitors , lithium salts , and selective serotonin reuptake inhibitors (SSRIs)), antiemetics , anticonvulsants /antiepileptics, anxiolytics , barbiturates , movement disorder (e.g., Parkinson's disease ) drugs, nootropics , stimulants (including amphetamines ), benzodiazepines , cyclopyrrolones , dopamine antagonists , antihistamines , cholinergics , anticholinergics , emetics , cannabinoids , and 5-HT (serotonin) antagonists .
The main classes of painkillers are NSAIDs , opioids , and local anesthetics .
For consciousness (anesthetic drugs)
Some anesthetics include benzodiazepines and barbiturates .
The main categories of drugs for musculoskeletal disorders are: NSAIDs (including COX-2 selective inhibitors ), muscle relaxants , neuromuscular drugs , and anticholinesterases .
Antibiotics , sympathomimetics , antihistamines , anticholinergics , NSAIDs , corticosteroids , antiseptics , local anesthetics , antifungals , and cerumenolytics.
Bronchodilators , antitussives , mucolytics , decongestants , inhaled and systemic corticosteroids , beta2-adrenergic agonists , anticholinergics , mast cell stabilizers , leukotriene antagonists .
Androgens , antiandrogens , estrogens , gonadotropin , corticosteroids , human growth hormone , insulin , antidiabetics ( sulfonylureas , biguanides / metformin , thiazolidinediones , insulin ), thyroid hormones , antithyroid drugs, calcitonin , diphosphonate , vasopressin analogues .
Antifungal , alkalinizing agents , quinolones , antibiotics , cholinergics , anticholinergics , antispasmodics , 5-alpha reductase inhibitor , selective alpha-1 blockers , sildenafils , fertility medications .
NSAIDs , anticholinergics , haemostatic drugs , antifibrinolytics , Hormone Replacement Therapy (HRT), bone regulators, beta-receptor agonists , follicle stimulating hormone , luteinising hormone , LHRH , gamolenic acid , gonadotropin release inhibitor , progestogen , dopamine agonists , oestrogen , prostaglandins , gonadorelin , clomiphene , tamoxifen , diethylstilbestrol .
Emollients , anti-pruritics , antifungals , antiseptics , scabicides , pediculicides , tar products, vitamin A derivatives , vitamin D analogues , keratolytics , abrasives , systemic antibiotics , topical antibiotics , hormones , desloughing agents, exudate absorbents, fibrinolytics , proteolytics , sunscreens , antiperspirants , corticosteroids , immune modulators.
Antibiotics , antifungals , antileprotics , antituberculous drugs , antimalarials , anthelmintics , amoebicides , antivirals , antiprotozoals , probiotics, prebiotics, antitoxins , and antivenoms.
Vaccines , immunoglobulins , immunosuppressants , interferons , and monoclonal antibodies .
Anti-allergics , antihistamines , NSAIDs , [ medical citation needed ] corticosteroids .
Tonics, electrolytes and mineral preparations (including iron preparations and magnesium preparations ), parenteral nutrition , vitamins , anti-obesity drugs , anabolic drugs , haematopoietic drugs, food product drugs.
Cytotoxic drugs , therapeutic antibodies , sex hormones , aromatase inhibitors , somatostatin inhibitors, recombinant interleukins , G-CSF , erythropoietin .
Contrast media .
A euthanaticum is used for euthanasia and physician-assisted suicide . Euthanasia is not permitted by law in many countries, and consequently, medicines will not be licensed for this use in those countries.
A single drug may contain single or multiple active ingredients .
The administration is the process by which a patient takes medicine. There are three major categories of drug administration: enteral (via the human gastrointestinal tract ), injection into the body, and by other routes ( dermal , nasal , ophthalmic , otologic , and urogenital ). [ 10 ]
Oral administration , the most common form of enteral administration, can be performed using various dosage forms including tablets or capsules and liquid such as syrup or suspension. Other ways to take the medication include buccally (placed inside the cheek), sublingually (placed underneath the tongue), eye and ear drops (dropped into the eye or ear), and transdermally (applied to the skin). [ 11 ]
They can be administered in one dose, as a bolus . Administration frequencies [ 12 ] are often abbreviated from Latin, such as every 8 hours reading Q8H from Quaque VIII Hora . The drug frequencies are often expressed as the number of times a drug is used per day (e.g., four times a day). It [ specify ] may include event-related information (e.g., 1 hour before meals, in the morning, at bedtime), or complimentary to an interval, although equivalent expressions may have different implications (e.g., every 8 hours versus 3 times a day). [ citation needed ]
In the fields of medicine, biotechnology , and pharmacology , drug discovery is the process by which new drugs are discovered. [ citation needed ]
Historically, drugs were discovered by identifying the active ingredient from traditional remedies or by serendipitous discovery. Later chemical libraries of synthetic small molecules , natural products , or extracts were screened in intact cells or whole organisms to identify substances that have a desirable therapeutic effect in a process known as classical pharmacology . Since sequencing of the human genome which allowed rapid cloning and synthesis of large quantities of purified proteins, it has become common practice to use high throughput screening of large compound libraries against isolated biological targets which are hypothesized to be disease-modifying in a process known as reverse pharmacology . Hits from these screens are then tested in cells and then in animals for efficacy . Even more recently, scientists have been able to understand the shape of biological molecules at the atomic level and to use that knowledge to design (see drug design ) drug candidates. [ citation needed ]
Modern drug discovery involves the identification of screening hits, medicinal chemistry , and optimization of those hits to increase the affinity , selectivity (to reduce the potential of side effects), efficacy/ potency , metabolic stability (to increase the half-life ), and oral bioavailability . Once a compound that fulfills all of these requirements has been identified, it will begin the process of drug development prior to clinical trials . One or more of these steps may, but not necessarily, involve computer-aided drug design .
Despite advances in technology and understanding of biological systems, drug discovery is still a lengthy, "expensive, difficult, and inefficient process" with a low rate of new therapeutic discovery. [ 13 ] In 2010, the research and development cost of each new molecular entity (NME) was approximately US$1.8 billion. [ 14 ] Drug discovery is done by pharmaceutical companies, sometimes with research assistance from universities. The "final product" of drug discovery is a patent on the potential drug. The drug requires very expensive Phase I, II, and III clinical trials, and most of them fail. Small companies have a critical role, often then selling the rights to larger companies that have the resources to run the clinical trials.
Drug discovery is different from Drug Development. Drug Discovery is often considered the process of identifying new medicine. At the same time, Drug development is delivering a new drug molecule into clinical practice. In its broad definition, this encompasses all steps from the basic research process of finding a suitable molecular target to supporting the drug's commercial launch.
Drug development is the process of bringing a new drug to the market once a lead compound has been identified through the process of drug discovery . It includes pre-clinical research (microorganisms/animals) and clinical trials (on humans) and may include the step of obtaining regulatory approval to market the drug. [ 15 ] [ 16 ]
Drug Development Process
Discovery: The Drug Development process starts with Discovery, a process of identifying a new medicine.
Development: Chemicals extracted from natural products are used to make pills, capsules, or syrups for oral use. Injections for direct infusion into the blood drops for eyes or ears.
Preclinical research : Drugs go under laboratory or animal testing, to ensure that they can be used on Humans.
Clinical testing: The drug is used on people to confirm that it is safe to use.
FDA Review: drug is sent to FDA before launching the drug into the market.
FDA post-Market Review: The drug is reviewed and monitored by FDA for the safety once it is available to the public.
The regulation of drugs varies by jurisdiction. In some countries, such as the United States, they are regulated at the national level by a single agency. In other jurisdictions, they are regulated at the state level, or at both state and national levels by various bodies, as is the case in Australia. The role of therapeutic goods regulation is designed mainly to protect the health and safety of the population. Regulation is aimed at ensuring the safety, quality, and efficacy of the therapeutic goods which are covered under the scope of the regulation. In most jurisdictions, therapeutic goods must be registered before they are allowed to be marketed. There is usually some degree of restriction on the availability of certain therapeutic goods depending on their risk to consumers. [ citation needed ]
Depending upon the jurisdiction , drugs may be divided into over-the-counter drugs (OTC) which may be available without special restrictions, and prescription drugs , which must be prescribed by a licensed medical practitioner in accordance with medical guidelines due to the risk of adverse effects and contraindications . The precise distinction between OTC and prescription depends on the legal jurisdiction. A third category, "behind-the-counter" drugs, is implemented in some jurisdictions. These do not require a prescription, but must be kept in the dispensary , not visible to the public, and be sold only by a pharmacist or pharmacy technician . Doctors may also prescribe prescription drugs for off-label use – purposes which the drugs were not originally approved for by the regulatory agency. The Classification of Pharmaco-Therapeutic Referrals helps guide the referral process between pharmacists and doctors.
The International Narcotics Control Board of the United Nations imposes a world law of prohibition of certain drugs. They publish a lengthy list of chemicals and plants whose trade and consumption (where applicable) are forbidden. OTC drugs are sold without restriction as they are considered safe enough that most people will not hurt themselves accidentally by taking it as instructed. [ 17 ] Many countries, such as the United Kingdom have a third category of "pharmacy medicines", which can be sold only in registered pharmacies by or under the supervision of a pharmacist.
Medical errors include over-prescription and polypharmacy , mis-prescription, contraindication and lack of detail in dosage and administration instructions. In 2000 the definition of a prescription error was studied using a Delphi method conference; the conference was motivated by ambiguity in what a prescription error is and a need to use a uniform definition in studies. [ 18 ]
In many jurisdictions, drug prices are regulated.
In the UK, the Pharmaceutical Price Regulation Scheme is intended to ensure that the National Health Service is able to purchase drugs at reasonable prices. The prices are negotiated between the Department of Health, acting with the authority of Northern Ireland and the UK Government, and the representatives of the Pharmaceutical industry brands, the Association of the British Pharmaceutical Industry (ABPI). For 2017 this payment percentage set by the PPRS will be 4,75%. [ 19 ]
In Canada, the Patented Medicine Prices Review Board examines drug pricing and determines if a price is excessive or not. In these circumstances, drug manufacturers must submit a proposed price to the appropriate regulatory agency. Furthermore, "the International Therapeutic Class Comparison Test is responsible for comparing the National Average Transaction Price of the patented drug product under review" [ 20 ] different countries that the prices are being compared to are the following: France, Germany, Italy, Sweden, Switzerland, the United Kingdom, and the United States [ 20 ]
In Brazil, the prices are regulated through legislation under the name of Medicamento Genérico ( generic drugs ) since 1999. [ 21 ]
In India, drug prices are regulated by the National Pharmaceutical Pricing Authority .
In the United States, drug costs are partially unregulated, but instead are the result of negotiations between drug companies and insurance companies. [ 22 ]
High prices have been attributed to monopolies given to manufacturers by the government. [ 23 ] New drug development costs continue to rise as well. Despite the enormous advances in science and technology, the number of new blockbuster drugs approved by the government per billion dollars spent has halved every 9 years since 1950. [ 24 ]
A blockbuster drug is a drug that generates more than $1 billion in revenue for a pharmaceutical company in a single year. [ 25 ] Cimetidine was the first drug ever to reach more than $1 billion a year in sales, thus making it the first blockbuster drug. [ 26 ]
In the pharmaceutical industry, a blockbuster drug is one that achieves acceptance by prescribing physicians as a therapeutic standard for, most commonly, a highly prevalent chronic (rather than acute) condition. Patients often take the medicines for long periods. [ 27 ]
Antibiotics first arrived on the medical scene in 1932 thanks to Gerhard Domagk ; [ 28 ] and were coined the "wonder drugs". The introduction of the sulfa drugs led to the mortality rate from pneumonia in the U.S. to drop from 0.2% each year to 0.05% ( i.e. , 1 ⁄ 4 as much) by 1939. [ 29 ] Antibiotics inhibit the growth or the metabolic activities of bacteria and other microorganisms by a chemical substance of microbial origin. Penicillin , introduced a few years later, provided a broader spectrum of activity compared to sulfa drugs and reduced side effects. Streptomycin , found in 1942, proved to be the first drug effective against the cause of tuberculosis and also came to be the best known of a long series of important antibiotics. A second generation of antibiotics was introduced in the 1940s: aureomycin and chloramphenicol . Aureomycin was the best known of the second generation. [ citation needed ]
Lithium was discovered in the 19th century for nervous disorders and its possible mood-stabilizing or prophylactic effect; it was cheap and easily produced. As lithium fell out of favor in France, valpromide came into play. This antibiotic was the origin of the drug that eventually created the mood stabilizer category. Valpromide had distinct psychotrophic effects that were of benefit in both the treatment of acute manic states and in the maintenance treatment of manic depression illness. Psychotropics can either be sedative or stimulant ; sedatives aim at damping down the extremes of behavior. Stimulants aim at restoring normality by increasing tone. Soon arose the notion of a tranquilizer which was quite different from any sedative or stimulant. The term tranquilizer took over the notions of sedatives and became the dominant term in the West through the 1980s. In Japan, during this time, the term tranquilizer produced the notion of a psyche-stabilizer and the term mood stabilizer vanished. [ 30 ]
Premarin (conjugated estrogens, introduced in 1942) and Prempro (a combination estrogen-progestin pill, introduced in 1995) dominated the hormone replacement therapy (HRT) during the 1990s. HRT is not a life-saving drug, nor does it cure any disease. HRT has been prescribed to improve one's quality of life. Doctors prescribe estrogen for their older female patients both to treat short-term menopausal symptoms and to prevent long-term diseases. In the 1960s and early 1970s, more and more physicians began to prescribe estrogen for their female patients. Between 1991 and 1999, Premarin was listed as the most popular prescription and best-selling drug in America. [ 30 ]
The first oral contraceptive, Enovid , was approved by FDA in 1960. Oral contraceptives inhibit ovulation and so prevent conception. Enovid was known to be much more effective than alternatives including the condom and the diaphragm. As early as 1960, oral contraceptives were available in several different strengths by every manufacturer. In the 1980s and 1990s, an increasing number of options arose including, most recently, a new delivery system for the oral contraceptive via a transdermal patch . In 1982, a new version of "the pill" was introduced, known as the biphasic pill . By 1985, a new triphasic pill was approved. Physicians began to think of "the pill" as an excellent means of birth control for young women. [ 30 ]
Stimulants such as Ritalin (methylphenidate) came to be pervasive tools for behavior management and modification in young children. Ritalin was first marketed in 1955 for narcolepsy ; its potential users were middle-aged and the elderly. It was not until some time in the 1980s along with hyperactivity in children that Ritalin came onto the market. Medical use of methylphenidate is predominantly for symptoms of attention deficit hyperactivity disorder (ADHD). Consumption of methylphenidate in the U.S. out-paced all other countries between 1991 and 1999. Significant growth in consumption was also evident in Canada, New Zealand, Australia, and Norway. Currently, 85% of the world's methylphenidate is consumed in America. [ 30 ]
The first minor tranquilizer was meprobamate . Only fourteen months after it was made available, meprobamate had become the country's largest-selling prescription drug. By 1957, meprobamate had become the fastest-growing drug in history. The popularity of meprobamate paved the way for Librium and Valium , two minor tranquilizers that belonged to a new chemical class of drugs called the benzodiazepines . These were drugs that worked chiefly as anti-anxiety agents and muscle relaxants . The first benzodiazepine was Librium. Three months after it was approved, Librium had become the most prescribed tranquilizer in the nation. Three years later, Valium hit the shelves and was ten times more effective as a muscle relaxant and anti-convulsant. Valium was the most versatile of the minor tranquilizers. Later came the widespread adoption of major tranquilizers such as chlorpromazine and the drug reserpine . In 1970, sales began to decline for Valium and Librium, but sales of new and improved tranquilizers, such as Xanax , introduced in 1981 for the newly created diagnosis of panic disorder, soared. [ 30 ]
Mevacor (lovastatin) is the first and most influential statin in the American market. The 1991 launch of Pravachol (pravastatin), the second available in the United States, and the release of Zocor (simvastatin) made Mevacor no longer the only statin on the market.
In 1998, Viagra was released as a treatment for erectile dysfunction. [ 30 ]
Using plants and plant substances to treat all kinds of diseases and medical conditions is believed to date back to prehistoric medicine . [ citation needed ]
The Kahun Gynaecological Papyrus , the oldest known medical text of any kind, dates to about 1800 BC and represents the first documented use of any kind of drug. [ 31 ] [ 32 ] It and other medical papyri describe Ancient Egyptian medical practices , such as using honey to treat infections and the legs of bee-eaters to treat neck pains.
Ancient Babylonian medicine demonstrated the use of medication in the first half of the 2nd millennium BC . Medicinal creams and pills were employed as treatments. [ 33 ]
On the Indian subcontinent, the Atharvaveda , a sacred text of Hinduism whose core dates from the second millennium BC, although the hymns recorded in it are believed to be older, is the first Indic text dealing with medicine. It describes plant-based drugs to counter diseases. [ 34 ] The earliest foundations of ayurveda were built on a synthesis of selected ancient herbal practices, together with a massive addition of theoretical conceptualizations, new nosologies and new therapies dating from about 400 BC onwards. [ 35 ] The student of Āyurveda was expected to know ten arts that were indispensable in the preparation and application of his medicines: distillation, operative skills, cooking, horticulture, metallurgy, sugar manufacture, pharmacy, analysis and separation of minerals, compounding of metals, and preparation of alkalis .
The Hippocratic Oath for physicians, attributed to fifth century BC Greece, refers to the existence of "deadly drugs", and ancient Greek physicians imported drugs from Egypt and elsewhere. [ 36 ] The pharmacopoeia De materia medica , written between 50 and 70 CE by the Greek physician Pedanius Dioscorides , was widely read for more than 1,500 years. [ 37 ]
Al-Kindi 's ninth century AD book, De Gradibus and Ibn Sina (Avicenna)'s The Canon of Medicine , covers a range of drugs known to the practice of medicine in the medieval Islamic world .
Medieval medicine of Western Europe saw advances in surgery compared to previously, but few truly effective drugs existed, beyond opium (found in such extremely popular drugs as the "Great Rest" of the Antidotarium Nicolai at the time) [ 38 ] and quinine . Folklore cures and potentially poisonous metal-based compounds were popular treatments. Theodoric Borgognoni , (1205–1296), one of the most significant surgeons of the medieval period, responsible for introducing and promoting important surgical advances including basic antiseptic practice and the use of anaesthetics . Garcia de Orta described some herbal treatments that were used. [ vague ]
For most of the 19th century, drugs were not highly effective, leading Oliver Wendell Holmes Sr. to famously comment in 1842 that "if all medicines in the world were thrown into the sea, it would be all the better for mankind and all the worse for the fishes". [ 27 ] : 21
During the First World War , Alexis Carrel and Henry Dakin developed the Carrel-Dakin method of treating wounds with an irrigation, Dakin's solution, a germicide which helped prevent gangrene .
In the inter-war period, the first anti-bacterial agents such as the sulpha antibiotics were developed. The Second World War saw the introduction of widespread and effective antimicrobial therapy with the development and mass production of penicillin antibiotics, made possible by the pressures of the war and the collaboration of British scientists with the American pharmaceutical industry .
Medicines commonly used by the late 1920s included aspirin , codeine , and morphine for pain; digitalis , nitroglycerin , and quinine for heart disorders, and insulin for diabetes. Other drugs included antitoxins , a few biological vaccines, and a few synthetic drugs. In the 1930s, antibiotics emerged: first sulfa drugs , then penicillin and other antibiotics. Drugs increasingly became "the center of medical practice". [ 27 ] : 22 In the 1950s, other drugs emerged including corticosteroids for inflammation , rauvolfia alkaloids as tranquilizers and antihypertensives, antihistamines for nasal allergies, xanthines for asthma, and typical antipsychotics for psychosis. [ 27 ] : 23–24 As of 2007, thousands of approved drugs have been developed . Increasingly, biotechnology is used to discover biopharmaceuticals . [ 27 ] Recently, multi-disciplinary approaches have yielded a wealth of new data on the development of novel antibiotics and antibacterials and on the use of biological agents for antibacterial therapy. [ 39 ]
In the 1950s, new psychiatric drugs, notably the antipsychotic chlorpromazine , were designed in laboratories and slowly came into preferred use. Although often accepted as an advance in some ways, there was some opposition, due to serious adverse effects such as tardive dyskinesia . Patients often opposed psychiatry and refused or stopped taking the drugs when not subject to psychiatric control.
Governments have been heavily involved in the regulation of drug development and drug sales. In the U.S., the Elixir Sulfanilamide disaster led to the establishment of the Food and Drug Administration , and the 1938 Federal Food, Drug, and Cosmetic Act required manufacturers to file new drugs with the FDA. The 1951 Humphrey-Durham Amendment required certain drugs to be sold by prescription. In 1962, a subsequent amendment required new drugs to be tested for efficacy and safety in clinical trials . [ 27 ] : 24–26
Until the 1970s, drug prices were not a major concern for doctors and patients. As more drugs became prescribed for chronic illnesses, however, costs became burdensome, and by the 1970s nearly every U.S. state required or encouraged the substitution of generic drugs for higher-priced brand names. This also led to the 2006 U.S. law, Medicare Part D , which offers Medicare coverage for drugs. [ 27 ] : 28–29
As of 2008, the United States is the leader in medical research , including pharmaceutical development. U.S. drug prices are among the highest in the world, and drug innovation is correspondingly high. In 2000, U.S.-based firms developed 29 of the 75 top-selling drugs; firms from the second-largest market, Japan, developed eight, and the United Kingdom contributed 10. France, which imposes price controls, developed three. Throughout the 1990s, outcomes were similar. [ 27 ] : 30–31
Controversies concerning pharmaceutical drugs include patient access to drugs under development and not yet approved, pricing, and environmental issues.
Governments worldwide have created provisions for granting access to drugs prior to approval for patients who have exhausted all alternative treatment options and do not match clinical trial entry criteria. Often grouped under the labels of compassionate use, expanded access , or named patient supply, these programs are governed by rules which vary by country defining access criteria, data collection, promotion, and control of drug distribution. [ 40 ]
Within the United States, pre-approval demand is generally met through treatment IND (investigational new drug) applications (INDs), or single-patient INDs. These mechanisms, which fall under the label of expanded access programs, provide access to drugs for groups of patients or individuals residing in the US. Outside the US, Named Patient Programs provide controlled, pre-approval access to drugs in response to requests by physicians on behalf of specific, or "named", patients before those medicines are licensed in the patient's home country. Through these programs, patients are able to access drugs in late-stage clinical trials or approved in other countries for a genuine, unmet medical need, before those drugs have been licensed in the patient's home country. [ citation needed ]
Patients who have not been able to get access to drugs in development have organized and advocated for greater access. In the United States, ACT UP formed in the 1980s, and eventually formed its Treatment Action Group in part to pressure the US government to put more resources into discovering treatments for AIDS and then to speed release of drugs that were under development. [ 41 ]
The Abigail Alliance was established in November 2001 by Frank Burroughs in memory of his daughter, Abigail. [ 42 ] The Alliance seeks broader availability of investigational drugs on behalf of terminally ill patients.
In 2013, BioMarin Pharmaceutical was at the center of a high-profile debate regarding expanded access of cancer patients to experimental drugs. [ 43 ] [ 44 ]
Essential medicines, as defined by the World Health Organization (WHO), are "those drugs that satisfy the health care needs of the majority of the population; they should therefore be available at all times in adequate amounts and in appropriate dosage forms, at a price the community can afford." [ 45 ] Recent studies have found that most of the medicines on the WHO essential medicines list, outside of the field of HIV drugs, are not patented in the developing world, and that lack of widespread access to these medicines arise from issues fundamental to economic development – lack of infrastructure and poverty. [ 46 ] Médecins Sans Frontières also runs a Campaign for Access to Essential Medicines campaign, which includes advocacy for greater resources to be devoted to currently untreatable diseases that primarily occur in the developing world. The Access to Medicine Index tracks how well pharmaceutical companies make their products available in the developing world. [ citation needed ]
World Trade Organization negotiations in the 1990s, including the TRIPS Agreement and the Doha Declaration , have centered on issues at the intersection of international trade in pharmaceuticals and intellectual property rights , with developed world nations seeking strong intellectual property rights to protect investments made to develop new drugs, and developing world nations seeking to promote their generic pharmaceuticals industries and their ability to make medicine available to their people via compulsory licenses .
Some have raised ethical objections specifically with respect to pharmaceutical patents and the high prices for drugs that they enable their proprietors to charge, which poor people around the world, cannot afford. [ 47 ] [ 48 ] Critics also question the rationale that exclusive patent rights and the resulting high prices are required for pharmaceutical companies to recoup the large investments needed for research and development. [ 47 ] One study concluded that marketing expenditures for new drugs often doubled the amount that was allocated for research and development. [ 49 ] Other critics claim that patent settlements would be costly for consumers, the health care system, and state and federal governments because it would result in delaying access to lower cost generic medicines. [ 50 ]
Novartis fought a protracted battle with the government of India over the patenting of its drug, Gleevec , in India, which ended up in a Supreme Court in a case known as Novartis v. Union of India & Others . The Supreme Court ruled narrowly against Novartis, but opponents of patenting drugs claimed it as a major victory. [ 51 ]
Pharmaceutical medications are commonly described as "ubiquitous" in nearly every type of environmental medium (i.e. lakes , rivers , streams , estuaries , seawater , and soil ) worldwide. [ 52 ] [ 53 ] [ 54 ] [ 55 ] Their chemical components are typically present at relatively low concentrations in the ng/L to μg/L ranges. [ 56 ] [ 54 ] The primary avenue for medications reaching the environment are through the effluent of wastewater treatment plants , both from industrial plants during production, and from municipal plants after consumption. [ 57 ] Agricultural pollution is another significant source derived from the prevalence of antibiotic use in livestock . [ 56 ]
Scientists generally divide environmental impacts of a chemical into three primary categories: persistence, bioaccumulation , and toxicity . [ 53 ] Since medications are inherently bio-active, most are naturally degradable in the environment, however they are classified as "pseudopersistent" because they are constantly being replenished from their sources. [ 52 ] These Environmentally Persistent Pharmaceutical Pollutants (EPPPs) rarely reach toxic concentrations in the environment, however they have been known to bioaccumulate in some species. [ 58 ] Their effects have been observed to compound gradually across food webs , rather than becoming acute, leading to their classification by the US Geological Survey as "Ecological Disrupting Compounds." [ 52 ] | https://en.wikipedia.org/wiki/Medication |
Medication therapy management , generally called medicine use review in the United Kingdom, is a service provided typically by pharmacists , medical affairs , and RWE scientists that aims to improve outcomes by helping people to better understand their health conditions and the medications used to manage them. [ 1 ] This includes providing education on the disease state and medications used to treat the disease state, ensuring that medicines are taken correctly, reducing waste due to unused medicines, looking for any side effects, and providing education on how to manage any side effects. [ 2 ] [ 3 ] The process that can be broken down into five steps: medication therapy review, personal medication record, medication-related action plan, intervention and or referral, and documentation and follow-up. [ 4 ] [ 5 ]
The medication therapy review has the pharmacist review all of the prescribed medications, any over the counter medications, and all dietary supplements an individual is taking. This allows the pharmacist to look for any duplications or dangerous drug interactions . [ 6 ] [ 7 ] This service can be especially valuable for people who are older, have several chronic conditions , take multiple medications, or are seen by multiple doctors. [ 8 ] [ 4 ] [ 5 ]
The goal of medication review is to improve health and reduce morbidity and mortality in patients by optimizing the use of their current medications. [ 3 ] Different hospital institutions and countries have different policies or approaches to medication review for their inpatients. [ 3 ] The effectiveness of a formal medication review program in people who are hospitalized has not been well studied. [ 3 ] There is some evidence that a medication review program reduces the number of people re-admitted to hospital and also may decrease the number of times they return to the emergency department. [ 3 ] The effects on morbidity and any improvements on the quality of a person's life are not clear. [ 3 ]
In 2014, the US Centers for Medicare and Medicaid Services required Part D plans to include an MTM program, [ 9 ] which led to an expansion of services offered. [ 10 ] MTM services are provided free to eligible patients enrolled in a plan. As of 2019, to be eligible a patient must have at least two (or three, for some plans) chronic conditions, take multiple drugs covered by Part D, and are predicted to exceed a preset amount in annual out of pocket costs for their covered Part D drugs (set at $3,967 in 2018 and $4,044 in 2019). [ 11 ] [ 12 ] Plans are permitted to expand MTM eligibility to patients not meeting the minimum required criteria if they so choose. [ 11 ]
As part of the minimum required services, plans must provide for a comprehensive medication review (CMR) once per year, usually conducted by a pharmacist. Per CMS guidance, the goal of the CMR is to "improve patients’ knowledge
of their prescriptions, over-the-counter (OTC) medications, herbal therapies and dietary supplements, identify and address problems or concerns that patients may have, and empower patients to self manage their medications and their health conditions." [ 11 ] The CMR is conducted in an interactive manner either in person or through telehealth . A pharmacist or other provider conducting a CMR will use information from various sources, such as the pharmacy fill records, the patient's pill bottles, a patient interview, and/or discussion with caregivers to identify potential improvements that can be made in the patient's therapy. [ 13 ] The pharmacist will then make any appropriate recommendations to the patient's doctor, as well as document their findings in a format similar to a SOAP note . [ 13 ] The patient must be provided a medication action plan with a list of their medications, directions, and any steps they need to take to improve their therapy (such as using reminders, organizing, stopping old medications, etc). [ 13 ] Most comprehensive medication reviews result in pharmacist intervention to recommend changes to therapy to a doctor, and/or recommendations to the patient to improve adherence/efficacy of their medications. [ 14 ] [ 15 ]
A targeted medication review (TMR, also called targeted intervention program or TIP) is a required service for eligible patients that focuses on a specific medication or disease state and is conducted once every three months. [ 11 ] The goal of a TMR program is to improve adherence to medication and identify and fix drug therapy problems common in chronic diseases such as nonadherence, duplicate therapy, or sub-optimal therapy. [ 13 ] The pharmacist or provider will contact the patient to ensure adherence, identify potential problems with the therapy, and make any appropriate recommendations to the prescriber. The provision of TMR services to patients with chronic diseases has been shown to decrease the number of inpatient admissions per 1000 patients by about 50 admissions per 1000 patients. [ 13 ]
A medicine use review (MUR) is an advanced service offered by pharmacies in the United Kingdom . It is part of the current contract pharmacies hold with the National Health Service (NHS). An MUR is an opportunity for patients to discuss their medicines with a qualified pharmacist. An MUR is a free NHS service that is held in a private consultation room at a local pharmacy. It is not meant to replace the role of the general practitioner but rather provide:
Pharmacies in the United kingdom are paid £28 for each Medicines Use Review undertaken, up to a maximum of 400 per pharmacy, per year. At least 70% of patients must be in one of the four target groups:
The introduction of pharmacists into GP surgeries means that the practice pharmacists can do more to ensure that reviews are carried out where necessary. [ 17 ]
There have been concerns over abuse of the system, whereby multiple pharmacies are using the system to charge the £28 fee for each 10- to 15-minute MUR, and pressuring pharmacists to meet targets for the number carried out, with the review more of a tick-box exercise than a benefit for the patient. There have also been cases of falsification of figures. [ 18 ]
The effectiveness of a medication review program for elderly people who require multiple medications (polypharmacy) is not clear and more research is needed to understand how to optimize medications in elderly inpatients. [ 19 ] | https://en.wikipedia.org/wiki/Medication_therapy_management |
Medicinal Chemistry Research is a peer-reviewed scientific journal of medicinal chemistry emphasizing the structure-activity relationships of biologically active compounds. [ 1 ] It was founded in 1991 by Alfred Burger ( University of Virginia ), who also founded the Journal of Medicinal Chemistry . [ 2 ] The journal is currently edited by Longqin Hu.
Alfred Burger served as its first editor-in-chief before passing on the mantle to Richard Glennon ( Virginia Commonwealth University ). [ 3 ] Stephen J. Cutler ( University of South Carolina ) then took over and served between 2002 and 2019. Longqin Hu ( Rutgers University–New Brunswick ) became editor in 2020. [ 4 ]
The journal is abstracted and indexed in the following bibliographic databases : [ 5 ]
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Medicinal Research Reviews is a bimonthly peer-reviewed scientific journal that publishes reviews on topics related to medicinal research. It is published by Wiley and was established in 1980. [ 1 ] The editor-in-chief is Amanda E. Hargrove ( Duke University ). [ 2 ]
The journal publishes critical reviews of topics include pathophysiology , genomics and proteomics , and clinical characteristics of important drugs.
The journal is abstracted and indexed in:
According to the Journal Citation Reports , the journal has a 2021 impact factor of 12.388. [ 6 ]
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Medicinal or pharmaceutical chemistry is a scientific discipline at the intersection of chemistry and pharmacy involved with designing and developing pharmaceutical drugs . Medicinal chemistry involves the identification, synthesis and development of new chemical entities suitable for therapeutic use. It also includes the study of existing drugs, their biological properties, and their quantitative structure-activity relationships (QSAR). [ 1 ] [ 2 ]
Medicinal chemistry is a highly interdisciplinary science combining organic chemistry with biochemistry , computational chemistry , pharmacology , molecular biology , statistics , and physical chemistry .
Compounds used as medicines are most often organic compounds , which are often divided into the broad classes of small organic molecules (e.g., atorvastatin , fluticasone , clopidogrel ) and " biologics " ( infliximab , erythropoietin , insulin glargine ), the latter of which are most often medicinal preparations of proteins (natural and recombinant antibodies , hormones etc.). Medicines can also be inorganic and organometallic compounds, commonly referred to as metallodrugs (e.g., platinum , lithium and gallium -based agents such as cisplatin , lithium carbonate and gallium nitrate , respectively). The discipline of Medicinal Inorganic Chemistry investigates the role of metals in medicine metallotherapeutics, which involves the study and treatment of diseases and health conditions associated with inorganic metals in biological systems. There are several metallotherapeutics approved for the treatment of cancer (e.g., contain Pt, Ru, Gd, Ti, Ge, V, and Ga), antimicrobials (e.g., Ag, Cu, and Ru), diabetes (e.g., V and Cr), broad-spectrum antibiotic (e.g., Bi), bipolar disorder (e.g., Li). [ 3 ] [ 4 ] Other areas of study include: metallomics , genomics , proteomics , diagnostic agents (e.g., MRI: Gd, Mn; X-ray: Ba, I) and radiopharmaceuticals (e.g., 99m Tc for diagnostics, 186 Re for therapeutics).
In particular, medicinal chemistry in its most common practice—focusing on small organic molecules—encompasses synthetic organic chemistry and aspects of natural products and computational chemistry in close combination with chemical biology , enzymology and structural biology , together aiming at the discovery and development of new therapeutic agents. Practically speaking, it involves chemical aspects of identification, and then systematic, thorough synthetic alteration of new chemical entities to make them suitable for therapeutic use. It includes synthetic and computational aspects of the study of existing drugs and agents in development in relation to their bioactivities (biological activities and properties), i.e., understanding their structure–activity relationships (SAR). Pharmaceutical chemistry is focused on quality aspects of medicines and aims to assure fitness for purpose of medicinal products. [ 5 ]
At the biological interface, medicinal chemistry combines to form a set of highly interdisciplinary sciences, setting its organic, physical , and computational emphases alongside biological areas such as biochemistry , molecular biology , pharmacognosy and pharmacology , toxicology and veterinary and human medicine ; these, with project management , statistics , and pharmaceutical business practices, systematically oversee altering identified chemical agents such that after pharmaceutical formulation , they are safe and efficacious , and therefore suitable for use in treatment of disease.
Discovery is the identification of novel active chemical compounds, often called "hits", which are typically found by assay of compounds for a desired biological activity . [ 6 ] Initial hits can come from repurposing existing agents toward a new pathologic processes, [ 7 ] and from observations of biologic effects of new or existing natural products from bacteria, fungi, [ 8 ] plants, [ 9 ] etc. In addition, hits also routinely originate from structural observations of small molecule "fragments" bound to therapeutic targets (enzymes , receptors, etc.), where the fragments serve as starting points to develop more chemically complex forms by synthesis. Finally, hits also regularly originate from en-masse testing of chemical compounds against biological targets using biochemical or chemoproteomics assays, where the compounds may be from novel synthetic chemical libraries known to have particular properties (kinase inhibitory activity, diversity or drug-likeness, etc.), or from historic chemical compound collections or libraries created through combinatorial chemistry . While a number of approaches toward the identification and development of hits exist, the most successful techniques are based on chemical and biological intuition developed in team environments through years of rigorous practice aimed solely at discovering new therapeutic agents.
Further chemistry and analysis is necessary, first to identify the "triage" compounds that do not provide series displaying suitable SAR and chemical characteristics associated with long-term potential for development, then to improve the remaining hit series concerning the desired primary activity, as well as secondary activities and physiochemical properties such that the agent will be useful when administered in real patients. In this regard, chemical modifications can improve the recognition and binding geometries ( pharmacophores ) of the candidate compounds, and so their affinities for their targets, as well as improving the physicochemical properties of the molecule that underlie necessary pharmacokinetic / pharmacodynamic (PK/PD), and toxicologic profiles (stability toward metabolic degradation, lack of geno-, hepatic, and cardiac toxicities, etc.) such that the chemical compound or biologic is suitable for introduction into animal and human studies. [ citation needed ]
The final synthetic chemistry stages involve the production of a lead compound in suitable quantity and quality to allow large scale animal testing, and then human clinical trials . This involves the optimization of the synthetic route for bulk industrial production, and discovery of the most suitable drug formulation . The former of these is still the bailiwick of medicinal chemistry, the latter brings in the specialization of formulation science (with its components of physical and polymer chemistry and materials science). The synthetic chemistry specialization in medicinal chemistry aimed at adaptation and optimization of the synthetic route for industrial scale syntheses of hundreds of kilograms or more is termed process synthesis , and involves thorough knowledge of acceptable synthetic practice in the context of large scale reactions (reaction thermodynamics, economics, safety, etc.). Critical at this stage is the transition to more stringent GMP requirements for material sourcing, handling, and chemistry. [ citation needed ]
The synthetic methodology employed in medicinal chemistry is subject to constraints that do not apply to traditional organic synthesis . Owing to the prospect of scaling the preparation, safety is of paramount importance. The potential toxicity of reagents affects methodology. [ 5 ] [ 10 ]
The structures of pharmaceuticals are assessed in many ways, in part as a means to predict efficacy, stability, and accessibility. Lipinski's rule of five focus on the number of hydrogen bond donors and acceptors, number of rotatable bonds, surface area, and lipophilicity. Other parameters by which medicinal chemists assess or classify their compounds are: synthetic complexity, chirality, flatness, and aromatic ring count.
Structural analysis of lead compounds is often performed through computational methods prior to actual synthesis of the ligand(s). This is done for a number of reasons, including but not limited to: time and financial considerations (expenditure, etc.). Once the ligand of interest has been synthesized in the laboratory, analysis is then performed by traditional methods (TLC, NMR, GC/MS, and others). [ 5 ]
Medicinal chemistry is by nature an interdisciplinary science, and practitioners have a strong background in organic chemistry, which must eventually be coupled with a broad understanding of biological concepts related to cellular drug targets. [ 11 ] Scientists in medicinal chemistry work are principally industrial scientists (but see following), working as part of an interdisciplinary team that uses their chemistry abilities, especially, their synthetic abilities, to use chemical principles to design effective therapeutic agents. The length of training is intense, with practitioners often required to attain a 4-year bachelor's degree followed by a 4–6 year Ph.D. in organic chemistry. Most training regimens also include a postdoctoral fellowship period of 2 or more years after receiving a Ph.D. in chemistry, making the total length of training range from 10 to 12 years of college education. [ 12 ] However, employment opportunities at the Master's level also exist in the pharmaceutical industry, and at that and the Ph.D. level there are further opportunities for employment in academia and government.
Graduate level programs in medicinal chemistry can be found in traditional medicinal chemistry or pharmaceutical sciences departments, both of which are traditionally associated with schools of pharmacy, and in some chemistry departments. However, the majority of working medicinal chemists have graduate degrees (MS, but especially Ph.D.) in organic chemistry, rather than medicinal chemistry, [ 13 ] and the preponderance of positions are in research, where the net is necessarily cast widest, and most broad synthetic activity occurs.
In research of small molecule therapeutics, an emphasis on training that provides for breadth of synthetic experience and "pace" of bench operations is clearly present (e.g., for individuals with pure synthetic organic and natural products synthesis in Ph.D. and post-doctoral positions, ibid.). In the medicinal chemistry specialty areas associated with the design and synthesis of chemical libraries or the execution of process chemistry aimed at viable commercial syntheses (areas generally with fewer opportunities), training paths are often much more varied (e.g., including focused training in physical organic chemistry, library-related syntheses, etc.).
As such, most entry-level workers in medicinal chemistry, especially in the U.S., do not have formal training in medicinal chemistry but receive the necessary medicinal chemistry and pharmacologic background after employment—at entry into their work in a pharmaceutical company, where the company provides its particular understanding or model of "medichem" training through active involvement in practical synthesis on therapeutic projects. (The same is somewhat true of computational medicinal chemistry specialties, but not to the same degree as in synthetic areas.) | https://en.wikipedia.org/wiki/Medicinal_chemistry |
The modern Medicine Wheel symbol was invented as a teaching tool in about 1972 by Charles Storm, aka Arthur C. Storm, writing under the name Hyemeyohsts Storm , in his book Seven Arrows and further expanded upon in his book Lightningbolt . [ 1 ] [ 2 ] : 5,168 It has since been used by various people to symbolize a variety of concepts, some based on Native American religions , others newly invented and of more New Age orientation. [ 2 ] : 5,7,181–183,187–189,193,218–219 [ 3 ] : 200 It is also a common symbol in some pan-Indian and twelve-step recovery groups. [ 4 ]
Charles Storm, pen name Hyemeyohsts Storm , was the son of a German immigrant who claimed to be Cheyenne ; he misappropriated and misrepresented Native American teachings and symbols from a variety of different cultures, claiming that they were Cheyenne, such as some symbolism connected to the Plains Sun dance , to create the modern Medicine Wheel symbol around 1972. [ 1 ] [ 5 ] [ 6 ] [ 7 ] [ 4 ] Anthropologist Alice Kehoe suspects that Storm took the idea of the medicine wheel from ahkoiyu , which are little model wheels used in games, and for decoration during rites by the Cheyenne, which were talked about in George Bird Grinnell 's 19th century ethnography titled The Cheyenne Indians: Their History and Lifeways . [ 3 ] : 200 [ 8 ] : 296,302,314 [ 9 ] : 455
Subsequently Vincent LaDuke (a New Age spiritual leader going by the name Sun Bear), who was of Ojibwe descent, started also using the Medicine Wheel symbol, combining the basic concept with pieces of disparate spiritual practices from various Indigenous cultures, and adding elements of new age and occult spiritualism. LaDuke self-published a newsletter and several books, and formed a group of followers that he named the Bear Tribe, of which he appointed himself the medicine chief. For a fee, his mostly wealthy and white followers attended his workshops and retreats, joined his "tribe", and could buy titles and honours that are traditionally reserved for respected elders and knowledge keepers. [ 1 ] [ 5 ] [ 7 ] [ 4 ] [ 10 ] [ 11 ] For these activities LaDuke was denounced and picketed by the American Indian Movement . [ 10 ]
Storm and LaDuke have been described as " plastic medicine men ". [ 10 ] They and others who have used the medicine wheel symbol to introduce their own ideas and concepts from other cultures into what they claim are Native American and First Nations teachings have been accused by traditional Natives and activists of harming and displacing traditional teachings for financial motives. [ 10 ] [ 12 ] [ 1 ] [ 13 ] [ 14 ] [ 15 ]
While some Indigenous groups that now use a version of the modern Medicine Wheel as a symbol have syncretized it with traditional teachings from their specific Native American or First Nations culture, and these particular teachings may go back hundreds, if not thousands of years, critics assert that the pan-Indian context it is usually placed in can too easily displace the unique, traditional teachings of sovereign tribes, bands and Nations, and in some cases even replace traditional ways with new age , fraudulent ones. [ 4 ]
New Age writers tend to centre the idea of the medicine wheel as an individualistic tool of personal development, and use a stylized version with the circle divided into coloured quadrants, with various personal qualities assigned to the colours and quadrants. This redefinition is in stark contrast to the Indigenous view of ceremony and sacred sites being rooted in the community rather than the individual. [ 16 ]
Many of the concepts introduced into the symbolism of the medicine wheel are arguably not pan-Indigenous and many are not grounded in traditional Indigenous worldviews, though many have to come to view them as such since the advent of the medicine wheel symbol. The typical medicine wheel symbol is divided into four quadrants, each with an associated set of qualities, characteristics, and concepts, with many of these coming from non-Indigenous sources and blended with New Age ideas. [ 2 ]
The four elements is a concept adopted from the Ancient Hindu beliefs of Pancha Bhuta and Ancient Greek philosophy of Empedocles . [ 17 ] [ 18 ]
The concepts of the four directions is not in accordance with many Indigenous worldviews that have six directions. [ 19 ] [ 20 ] Moreover, Cheyenne Elders and religious leaders do not typically teach cosmology by referring to the cardinal directions, as Storm did in his book. Rather, they explain cosmology by starting with the vertical, going through the divisions starting with Otatavoom (the Blue Sky-Space) and going to Nasthoaman (the Deep Earth). [ 21 ] [ 22 ] Moreover, the sacred cardinal directions in Cheyenne culture are closer to Northeast, Northwest, Southeast, and Southwest, not the North, South, East, and West as described by Storm. [ 13 ]
Though some Indigenous North American cultures, such as the Arapaho , view life as having four stages, [ 23 ] the Anishinaabe view life as having seven stages (according to the Miikaans Teaching) [ 24 ] [ 25 ] and the Eastern Cree have five stages. [ 26 ]
Though some Indigenous nations have traditional beliefs about people with a different skin colour in their sacred stories, the division of humans into four races is not traditional or universal, but is instead founded in scientific racism and the racist views of early anthropology and biology, notably Carl Linnaeus' classifications as Americanus (red), Europeanus (white), Asiaticus (yellow), and Africanus (black). [ 27 ]
The concept of the divisions of the mind, heart/spirit, body, and soul derive from the Ancient Greeks and Christian Neoplatonists . [ 28 ]
Some Indigenous nations divide the year into four seasons , but the Cheyenne, which Storm based his book on, have six to eight seasons. [ 21 ] Furthermore, the Gwich'in , the Ojibwe , the Cherokee , as well as nations in Virginia and most of the Southeastern US view the year as having five seasons. [ 29 ] [ 30 ] [ 31 ] Some nations of the Pacific Northwest Coast, such as the Haida , divide the year into two seasons, [ 31 ] while the Lakota and Kiowa have four seasons of unequal length, [ 31 ] [ 32 ] and the Woodland Cree have six seasons. [ 33 ]
The concept of the year as a wheel can be found in the Wicca and Modern paganism calendar known as the Wheel of the Year , which was published prior to Storm's publishing of the modern Medicine Wheel symbol and concept. [ 34 ]
Words for things like " Mother Earth " in Cree ( okâwîmâwaskiy ) are believed to be a contemporary concept from pan-Indigenous or new age influences because the word does not follow proper Cree grammar, and the classifications of mineral , plant , animal , and human does not fit into many Indigenous language structures. [ 35 ] [ 36 ]
Not all Indigenous nations use the same sacred medicines, as yucca , mescal , and peyote are also considered core sacred medicines by some nations, kinnikinnick was used ceremonially by some cultures, in addition to the more typically cited sage , cedar , sweet grass , and tobacco . [ 37 ] Furthermore, not all Indigenous nations use the four medicines, such as the Coast Salish who traditionally did not use tobacco [ 38 ] : 27 , and some Métis Elders who prefer tea and jam, and sometimes a blanket, to being offered tobacco. [ 39 ]
Storm has the colours out of order for Cheyenne teachings: East should be red instead of yellow, South should be green not red, and the four colours are white, red, green, and black. [ 22 ] [ 40 ] Furthermore, the Cheyenne colours are not the vivid colours used by Storm, but rather earth tones. [ 13 ] [ 41 ] [ 40 ]
The association of animals, commonly listed as bison , bear , wolf , and deer , (listed as buffalo , eagle , mouse , and bear in Storm's original description [ 41 ] ) with the quadrants is an example of diluted totemism . [ 2 ] In Cheyenne culture, which Storm claimed to base the teachings on, the animal associated with the North is the albino bison, and the dragonfly, vovetass , is associated with both the North and the South because it changes colour during the summer, from green to white. [ 22 ]
Though some of the concepts are founded in traditional Indigenous teachings, many are not and have resulted in confusion due to misinformation . [ 4 ] [ 11 ] : 141
Wolastoqew academic Andrea Bear Nicholas argues that the broad adoption of the medicine wheel with little critical assessment and historical understanding of its fraudulent origins has effectively and almost totally displaced the unique oral traditions of many Indigenous nations. She views the medicine wheel as another example of ongoing colonial assault against Indigenous cultures, and has criticized academia for not doing more to protect traditional Indigenous cultures. [ 4 ]
Co-founder and former president of the American Indian Historical Society, Rupert Costo , heavily criticized Storm's book Seven Arrows in which he introduced his medicine wheel concept, stating that Storm was "vulgarizing one of the most beautiful but least known religions of Man." [ 15 ]
"This book, Seven Arrows , will bring disgrace to Harper and Row.... Its content falsifies and desecrates the traditions and religion of the Northern Cheyenne, which it purports to describe. ... If he is indeed Indian (and the tribal chairman states, 'I don't know how he ever got on the rolls,') then shame on him for making a blasphemous travesty of the Cheyenne Way in Seven Arrows . The color plates are a solid disaster, in extremely poor taste, and in fact the end result desecrates the Cheyenne religion. ... The designs are actually blasphemous to Cheyenne religion, portraying Christian religious motifs in the worst possible manner, making a mockery of the religious beliefs and the theological systems of the people. ... There are so many irreligious and irreverent inaccuracies in this book.... to many Cheyenne people ... the reaction to Seven Arrows was disbelief and anger. It was ... based upon a falsification and desecration of Cheyenne beliefs and religion. ... The book is a White Man's interpretation of the Cheyenne. A reader searching for an understanding of the true beauty and profoundly moving religion of the Cheyenne people will not find it in this book. ...this author ... has no religious or secular status in the tribe."
The Northern Cheyenne Tribal Council officially condemned Storm's book Seven Arrows , citing numerous inaccuracies, as did Cheyenne Elders such as Joe Little Coyote. The book's publisher, Harper and Row , paid US$ 7,500 in reparations (intended to be "all profits presently accrued to Seven Arrows as well as all future profits earned by it.") each to the Northern and Southern Cheyenne, and reclassified the book as fiction. [ 15 ] [ 42 ] [ 22 ]
"Perhaps the most disturbing aspect of Mr. Chuck Storm's book Seven Arrows is the fact that some of the beliefs which he presents in his book as having been derived from our spiritual ways are completely unfounded and extremely repugnant to the sensitivities of our people who are knowledgeable and qualified to speak about such things, not merely as the product of imagination, but as the result of actual lived experience."
In reviewing Storm's book Seven Arrows , anthropologist John H. Moore criticized the book and how Storm inaccurately portrayed Cheyenne culture, skipping over important cultural details practised by Cheyenne cultural teachers, elevating minor elements of Cheyenne religion to undeserved major significance, dismissing cultural values, getting details mixed up, and adding things.
"Several books would be required to correct the compounded inaccuracies of Storm's version of Cheyenne tradition. The frustration of even attempting to do this has prompted a widespread outrage among religious Cheyennes. The Northern Cheyenne Tribal Council has condemned the book and asked that its use be discouraged. The calmest comment that I have received from a Cheyenne is from a member of the Tribal Council who described the book as 'complete B.S. from cover to cover. ' "
Both Storm and LaDuke have been criticized for commercializing and distorting Indigenous spirituality, including the medicine wheel. [ 2 ] : 239 [ 11 ] : 13,15 [ 10 ] : 324 [ 3 ] : 200
Indigenous activists protested and distributed flyers at a lecture given by Storm in San Francisco in February 1995, with the bold title "STOP EXPLOITING THE SACRED TRADITIONS OF AMERICAN INDIAN PEOPLE!!!", which began by saying:
We are members of the Bay Area American Indian community, and we are outraged by non-Indian wannabes and would-be gurus of 'the New Age' shamelessly exploiting and mocking our sacred religious traditions.... These sacred ways have enabled our people to survive five centuries of genocide. We will not allow these most sacred gifts to be desecrated and abused.... OUR SACRED SPIRITUAL PRACTICES ARE NOT FOR SALE, AND IF YOU TRY TO STEAL THEM FROM US, YOU ARE GUILTY OF SPIRITUAL GENOCIDE." [ 1 ]
The flyer distributed at Storm's San Francisco lecture was accompanied by a document titled "American Indian International Tribunal Elder’s Statement" that concluded with "Our young people are getting restless. They have said they will take care of those who are abusing our ceremonies and sacred objects in their own way." [ 1 ]
The Colorado chapter of the American Indian Movement confronted Sun Bear during one of his $500/head weekend-long "spiritual retreat". [ 16 ]
Lakota leader Rick Williams has criticized Sun Bear 's eclectic use of combined elements from different tribes, saying it creates a dangerous spiritual imbalance. He argues that every part of different Indigenous cultures' traditions serves a specific purpose, and that mixing elements between cultures will not only lead to the purposes being distorted and lost, but can potentially endanger the practitioner. [ 10 ]
Anthropologist Alice Keheo writes that Native medicine wheel rites, along with other Indigenous observance of the cyclical patterns in nature and life , are one of the reasons Natives are stereotyped as more spiritual than non-Natives. [ 3 ] : 195–196
Distortions of Indigenous culture, and thus identity, using things like Storm and LaDuke's medicine wheel, is criticized as 'killing off' real Indigenous cultures and displacing them by fictional Indigenous identities and cultures. The denial of agency in dismissing the concerns, wishes, and traditional cultures of Indigenous people through popularizing such works as Seven Arrows is criticized as continuing the indignity of desecrating, mocking and abusing Indigenous traditional ceremonies and spiritual practices. [ 12 ]
Ironically, as Bear Nicholas notes, objections and criticism about the medicine wheel symbol as a dangerous and false invented tradition are now condemned by many as disrespectful to tradition. [ 4 ]
Among users of the medicine wheel symbol, variations exist. The axes of the medicine wheel might also be rotated to be vertical. The quadrants can be rotated into a different arrangement and the order of the colours can be different, depending on the community. Meanings and associations with the colours also vary between nations. [ 43 ] Some Anishinaabe communities add a circle in the centre, often coloured green, to represent balance. [ 44 ] [ 45 ] [ 46 ] The black quadrant is often replaced with a blue quadrant in some Cree and Ojibwe communities. [ 47 ] [ 48 ] Métis occasionally add a circle with the Métis flag or a green circle in the centre or use the symbol of a Red River cart wheel overlaid on the medicine wheel. [ 49 ] [ 50 ] [ 51 ] Some versions of the medicine wheel consist of a hoop with two perpendicular axes connected to the hoop, and half of each axes and a connected quadrant of the hoop are coloured with the centre often left uncoloured. [ 52 ] [ 53 ] [ 54 ] Some Christian groups have incorporated the Christian cross into the medicine wheel in a manner similar to the Celtic cross . [ 55 ] In addition to the variations between Indigenous nations, there are also variations used within Indigenous nations, and not all Indigenous nations have adopted the medicine wheel, so care must be taken to not generalize. [ 56 ]
These examples are not a definitive list of medicine wheel designs and this is not an exhaustive list of the variations that exist. Variations exist between and within Indigenous nations, and no one design represents all Indigenous nations. These are provided as examples only. | https://en.wikipedia.org/wiki/Medicine_wheel_(symbol) |
The Medicines Discovery Catapult ( MDC ) is the United Kingdom's catapult centre for medicine research and innovation, headquartered at Alderley Park in Cheshire .
The intention to form the company was announced by the Chancellor on 13 July 2015 with funding of £5m, on a visit to Cheshire. It would be part of the Northern Powerhouse initiative. [ 1 ]
The Medicines Technologies Catapult was established in December 2015, [ 2 ] funded by a £10m grant from Innovate UK and based at the Alderley Park science park in Cheshire. [ 3 ] On 1 March 2016 its name changed to the Medicines Discovery Catapult. [ 2 ] Further funding of approximately £10m per year was secured from Innovate UK for the years 2018 to 2023. [ 3 ]
The PMC was based in Cambridge and had regional centres of excellence at Belfast, Glasgow, Cardiff, Oxford, Leeds and Manchester. It worked with precision medicine . It started from April 2015, and worked with regional parts of the Diagnostic Evidence Cooperative and Academic Health Science Networks (AHSN). [ citation needed ]
On 26 June 2017 it was announced that the PMC would close, with most of its functions transferred to the MDC. [ 4 ] The Leeds site is now the Leeds Centre for Personalised Medicine and Health.
A not-for-profit company, the MDC works with a range of UK innovators to advance projects and products towards clinical impact. In 2019, the company stated that it worked in four sectors: [ 3 ]
In the same year, the number of staff increased from 40 to 75, and the company reported that its income comprised £8.5m from Innovate UK and £152,000 from collaborative research and development. After charging £7.1m to administrative expenses, the company reported a loss for the year of £16,000. [ 3 ]
In 2020, the company was given the task of setting up one of the first PCR analysis centres for COVID-19 tests – known as Lighthouse labs – elsewhere at the Alderley Park site. [ 5 ] [ 6 ] By 2021, this centre employed over 700 staff and had a stated capacity of 80,000 test samples per day. [ citation needed ]
Dr Robin Brown has been the company's chairman since July 2018; [ 3 ] he has a PhD in molecular biology and has worked in venture capital at Advent Healthcare . [ 7 ] The company has no shareholders. [ 3 ]
Previously, Professor Graham Boulnois was chairman from January 2016; he was head of research from 1992 to 2000 at Zeneca Pharmaceuticals in Cheshire, and Professor of Microbiology from 1984 to 1992 at the University of Leicester . [ 8 ]
This article about an organisation in the United Kingdom is a stub . You can help Wikipedia by expanding it .
This article about medicinal chemistry is a stub . You can help Wikipedia by expanding it . | https://en.wikipedia.org/wiki/Medicines_Discovery_Catapult |
Medicon Valley is a leading international life-sciences cluster in Europe , spanning the Øresund Region of eastern Denmark and southern Sweden . It is one of Europe's strongest life science clusters, with many life science companies and research institutions located within a relatively small geographical area. The name has officially been in use since 1997.
Major life science sectors of the Medicon Valley cluster includes pharmacology , biotechnology , health tech and medical technology. It is specifically known for its research strengths in the areas of neurological disorders , inflammatory diseases , cancer and diabetes .
The population of Medicon Valley reaches close to 4 million inhabitants. In 2008, 60% of Scandinavian pharmaceutical companies were located in the region. The area includes 17 universities, 32 hospitals, and more than 400 [ 1 ] life science companies. 20 are large pharmaceutical or medical technology firms and 170 are dedicated biotechnology firms. Between 1998 and 2008, 100 new biotechnology and medical technology companies were created here. The biotechnology industry alone employs around 41,000 people in the region, 7,000 of whom are academic researchers. [ 2 ]
International companies with major research centres in the region include Novo Nordisk , Novozymes-Novonesis , Baxter , Lundbeck , Leo Pharma , Genmab , Bavarian Nordic , Zealand Pharma , HemoCue and Ferring Pharmaceuticals . There are more than 7 science parks in the region, all with a significant focus on life science, including the Medicon Village in Lund, established in 2010. Companies within Medicon Valley account for more than 20% of the total GDP of Denmark and Sweden combined. [ 3 ] [ 4 ]
Medicon Valley is promoted by Invest in Skåne and Copenhagen Capacity . [ 5 ]
Many of the region's universities have a strong heritage in biological and medical research and have produced several Nobel Prize winners. [ 6 ] The almost century-long presence of a number of research-intensive and fully integrated pharmaceutical companies, such as Novo Nordisk, H. Lundbeck and LEO Pharma, has also contributed significantly to the medical research and business development of the region by strengthening abilities within applied research, attracting suppliers and producing spin-offs. [ 7 ]
In 2011, the organisations of MVA and Invest in Skåne , launched the concept of Beacons. Beacons are projects for creating world-leading cross-disciplinary research environments with a focus on areas where there are considerable potential for synergies in Medicon Valley specifically. After a long thorough selection process, the four Beacons of systems biology , structural biology , immune regulation and drug delivery were approved. [ 8 ]
The Medicon Valley issues the quaternal life science magazine "Medicon Valley". [ 9 ]
Science parks in Medicon Valley includes: | https://en.wikipedia.org/wiki/Medicon_Valley |
Medicon Valley Alliance (or MVA for short) is the Danish - Swedish cluster organisation representing human life sciences in the cross-border region of Medicon Valley . As a non-profit member organisation, Medicon Valley Alliance (MVA) carries out initiatives on behalf of the local life science community in order to create new research and business opportunities – initiatives which members would not be able to implement individually, and with the aim of strengthening the development of Medicon Valley.
MVA's member base comprises biotech , medtech and pharma companies of all sizes, CRO's and CMO's, as well as public organizations, universities, science parks , investors , and various business service providers .
MVA is committed to facilitate economic growth , increased competitiveness and employment in Medicon Valley, and is furthermore committed to raise the international recognition of Medicon Valley with the aim of attracting labour, investments, and partners. MVA accomplish this by enhancing local networks, improving local framework conditions, increasing the visibility of Medicon Valley and facilitating international relations to companies and research institutions around the world.
There are currently +300 MVA-members including numerous big and small private biotech companies and public sector research institutions. Among the most prominent members are Novo Nordisk , Technical University of Denmark , University of Lund and University of Copenhagen
The current CEO of Medicon Valley Alliance is Anette Stenberg, following Petter Hartman and Stig Jørgensen.
Chairman of the board is CEO of Alligator Bioscience , Søren Bregenholt. Deputy chairman is Ulf G. Andersson, CEO of MEDEON .
MVA participants comprise academic departments, regions (hospital managers), states, research, pharmaceutical and medical firms, CROs, CMOs, technology parks, developers, market service providers and other Medicon Valley organizations. [ 1 ] | https://en.wikipedia.org/wiki/Medicon_Valley_Alliance |
Medio is a business-to-business mobile web analytics provider based in Seattle , Washington. The company processes pre-existing data [ 2 ] to provide historic and predictive analytics . Medio is built on a cloud-based [ 3 ] Hadoop platform and is designed to interpret big data for mobile enterprise. Medio has had partners including: IBM , Rovio , [ 4 ] Verizon , T-Mobile , [ 5 ] ABC , and Disney . [ 6 ]
Medio was founded in 2004 by Brian Lent, Bill Bryant, David Bluhm, and Michael Libes and employed 40 people. [ 7 ] Founded to be the ' Google ' of mobile search engines, [ 8 ] Medio was backed by $30 million in initial venture funding from companies including: Accel Partners , Mohr Davidow Ventures , and Frazier Technology Ventures .
Medio received $11 million more in 2006 [ 9 ] to create a mobile analytics search engine capable of searching for ringtones, graphics, and internet-delivered information. [ 8 ] This sparked employment to over 100 employees for some time, but in 2009 Google released their new mobile search engine. Rob Lilleness, who joined the company as President and COO in 2007 and was subsequently named CEO in 2009, took that as an opportunity to refocus as a predictive analytics and data science provider, using their recommendations engine as a key component of their newly focused company. [ 10 ] The shift resulted in lay-offs of much of the staff, scaling back to nearly 60 employees. [ 11 ]
By the end of 2010, the company became profitable, nearly tripling its sales from previous years. [ 12 ] Medio grew to 70 employees with a total of $44 million in venture funding. [ 6 ]
On July 1, 2014, Medio was acquired by Nokia. [ 13 ] [ 14 ] | https://en.wikipedia.org/wiki/Medio_(company) |
Medipix is a family of photon counting and particle tracking pixel detectors developed by an international collaboration, hosted by CERN . [ 1 ]
These are hybrid detectors as a semiconductor sensor layer is bonded to a processing electronics layer.
The sensor layer is a semiconductor, such as silicon , GaAs , or CdTe in which the incident radiation makes an electron hole/cloud. The charge is then collected to pixel electrodes and, via bump bonds, conducted to the CMOS electronics layer.
The pixel electronics first amplifies the signal and then compares the signal amplitude with a pre-set discrimination level (an energy threshold). The subsequent signal processing depends on the type of device. A standard Medipix detector increases the counter in the appropriate pixel if the signal is above the discrimination level. The Medipix device also contains an upper discrimination level and hence only signals within a range of amplitude could be accepted (within an energy window).
Timepix devices offer two more modes of operation in addition to the counting. The first one is so called “Time-over-Threshold” mode ( Wilkinson type analog-to-digital converter ). It is a mode where the counter in each pixel records the number of clocks for which the pulse remains above the discrimination level. This number is proportional to the energy of detected radiation. This mode is useful for particle tracking applications or for direct spectral imaging.
The second mode of the Timepix chip is “Time-of-arrival”, in which pixel counters record time between a trigger and detection of radiation quanta with energy above the discrimination level. This mode of operation finds use in time of flight (ToF) applications, for instance in neutron imaging.
Every individual hit of radiation is processed by the electronics integrated in each pixel this way, therefore the device could be considered as 65 536 individual counting detectors or even spectrometers. The energy discriminators are adjustable. Therefore, scanning with their level it is possible to measure over frequency-bands of the incoming radiation; thus enabling spectroscopic x-ray imaging.
Medipix-2, Timepix, and Medipix-3 are all 256×256 pixels, each 0.055 mm (55 μm) square, forming a total area 14.08 mm × 14.08 mm. Larger area detectors can be created by bump-bonding many chips to larger monolithic sensors. Detectors of sizes from 2x2 to 2x4 chips are commonly used. Even larger, gapless areas could be created using the edgeless sensor technology. Medipix/Timepix chips each have its own sensor. These assemblies are tiled next to each other to create nearly arbitrarily sized detector arrays (the largest build using this technology has 10x10 chips, hence 14x14 cm and 2560x2560 pixels [ 2 ] ).
Photon counting pixel detectors represent the next generation of radiation imaging detectors. The photon counting technology overcomes limitations of current imaging devices. Comparison of photon counting with existing technologies is in the following table:
Medipix-1 was the first device of the Medipix family. It had 64x64 pixels of 170 μm pitch. Pixels contained one comparator (threshold) with 3-bit per-pixel offset adjustment. The minimum threshold was ~5.5 keV. The counter depth was 15-bit. The maximum count rate per pixel was 2 MHz per pixel.
Medipix-2 is the successor of Medipix-1. The pixel pitch was reduced to 55 μm and the pixel array is of 256x256 pixels. Each pixel has two discrimination levels (upper and lower threshold) each adjustable individually in pixels using a 3-bit offset. The maximum count rate is about 100 kHz per pixel (however in pixels with 9x smaller area compared to Medipix-1).
Medipix-2 MXR is an improved version of Medipix-2 device with better temperature stability, pixel counter overflow protection, increased radiation hardness and many other improvements.
Timepix is device conceptually originating from Medipix-2. It adds two more modes to the pixels, in addition to counting of detected signals: Time-over-Threshold (TOT) and Time-of-Arrival (TOA). The detected pulse height is recorded in the pixel counter in the TOT mode. The TOA mode measures time between trigger and arrival of the radiation into each pixel.
Medipix-3 is the latest generation of photon counting devices for X-ray imaging. The pixel pitch remains the same (55 μm) as well as the pixel array size (256x256). It has better energy resolution through real time correction of charge sharing. It also has multiple counters per pixel that can be used in several different modes. This allows for continuous readout and up to eight energy thresholds.
Timepix-3 is a successor of the Timepix chip. One of the biggest distinguishing changes is the approach to the data readout. All previous chips used the frame-based readout, i.e. the whole pixel matrix was read out at once. Timepix-3 has event-based readout where values recorded in pixels are read out immediately after the hit together with coordinates of the hit pixel. The chip therefore generates a continuous stream of data rather than a sequence of frames. The next major difference compared to the previous Timepix chip is the ability to measure the hit amplitude simultaneously with the time of arrival. Other parameters such as energy and timing resolution were also improved compared to the original Timepix chip.
Timepix-4 is the successor of the Timepix-3 chip. It has general stronger specifications for instance its time-of-arrival resolution is 195 ps, 8 times faster than Timepix-3, it also has a larger pixelmatrix of 512x448 pixels and can handle 8 times higher data rates. [ 3 ]
The digital data recorded by Medipix/Timepix devices are transferred to a computer via readout electronics. The readout electronics is also responsible for setup and control of the detector parameters. Several readout systems were developed within the Medipix collaboration
Muros was one of the first readout systems of Medipix detectors. Muros was developed at Nikhef , Amsterdam , The Netherlands . It was relatively compact readout enabling access to all features of the detector. It allowed maximum frame rate of cca 30 frames/s with a single chip.
This electronics was developed at IEAP - CTU , Czech Republic . It provides a lower frame rate compared to Muros, but the electronics was integrated into a box not larger than a pack of cigarettes. Moreover, no special PC hardware card was needed as it was in case of Muros. Therefore, the USB interface become quickly the most used readout within the Medipix collaboration and its partners.
Relaxd is a readout electronics developed at Nikhef . The data is transferred to PC via 1 Gbit/s Ethernet connection. The maximum frame rate is at level of 100 frame/s.
Fitpix is the next generation of the USB interface developed by the group in Prague. The electronics implements the parallel Medipix/Timepix readout and therefore the maximum frame rate reaches 850 frame/s. It supports also the serial readout with frame rate of 100 frames/s.
Minipix is a miniaturized integrated chip+readout electronics device developed by ADVACAM s.r.o. in Prague . The whole system has size of a USB flash drive . Several of these devices were used on the International Space Station as radiation monitoring systems. [ 4 ]
Spidr3 is powerful readout electronics for the TimePix3 and MediPix3 chip. The readout rate for the MediPix3 is about 12500 frames per second and for the TimePix3 of 120 Million Hits per second. The data are transferred by a powerful 10 GB optical fiber connection. The chip and readout system is developed together with Nikhef and Amsterdam Scientific Instruments.
Both systems are developed at Diamond Light Source , UK, for Medipix3 readout and applications at synchrotrons. Merlin is available with CdTe sensors from Quantum Detectors who are collaborating on further development with Diamond Light Source.
Lambda is a high-speed (2,000 fps) big area (12 chips) readout systems developed at DESY . Lambda is available with high-Z sensor options, such as GaAs (Gallium-Arsenide) and CdTe (Cadmium-Telluride).
MARS is a gigabit Ethernet readout accommodating up to 6 Medipix 2 or Medipix 3 detectors. The electronics was developed at University of Otago , Christchurch , New Zealand .
X-ray imaging is the primary application field of Medipix detectors. Medipix offers to the X-ray imaging field in particular an advantage in higher dynamic range and energy sensitivity. [ 5 ] Examples of X-ray images from selected X-ray imaging application fields are:
Timepix-based detectors from the Medipix2 Collaboration have been flown on the International Space Station since 2013, and on the first flight test (EFT-1) of NASA's new Orion Multi-Purpose Crew Vehicle in December 2014. Current plans call for similar devices to be flown as the primary radiation area monitors on the future initial crewed Orion missions.
The detectors may also find applications in astronomy , high energy physics , medical imaging , and X-ray spectroscopy . | https://en.wikipedia.org/wiki/Medipix |
The Mediterranean Biogeographic Region is the biogeographic region around and including the Mediterranean Sea .
The term is defined by the European Environment Agency as applying to the land areas of Europe that border on the Mediterranean Sea, and the corresponding territorial waters.
The region is rich in biodiversity and has many endemic species.
The term may also be used in the broader sense of all the lands of the Mediterranean Basin , or in the narrow sense of just the Mediterranean Sea.
The European Commission defines the Mediterranean Biogeographic Region as consisting of the Mediterranean Sea, Greece, Malta, Cyprus, large parts of Portugal, Spain and Italy, and a smaller part of France. [ 1 ] The region includes 20.6% of European Union territory. [ 2 ]
The region has cool humid winters and hot dry summers. [ 3 ] Wladimir Köppen divided his "Cs" mediterranean climate classification into "Csa" with a highest mean monthly temperature over 22 °C (72 °F) and "Csb" where the mean monthly temperature was always lower than 22 °C (72 °F). [ 4 ] The region may also be subdivided into dry zones such as Alicante in Spain, and humid zones such as Cinque Terre in Italy. [ 5 ]
The region has generally hilly terrain and includes islands, high mountains, semi-arid steppes and thick Mediterranean forests, woodlands, and scrub with many aromatic plants .
There are rocky shorelines and sandy beaches.
The region has been greatly affected by human activity such as livestock grazing, cultivation, forest clearance and forest fires.
In recent years tourism has put greater pressure on the shoreline environment. [ 3 ]
The Mediterranean Biogeographic Region is rich in biodiversity and has many endemic species.
The region has more plants species than all the other biogeographical regions of Europe combined. [ 6 ] The wildlife and vegetation are adapted to the unpredictable weather, with sudden downpours or strong winds.
Coastal wetlands are home to endemic species of insects, amphibians and fish, which provide food for large flocks of waders and dabbling ducks .
The sea is also rich in marine life, including many endemic species.
The shallow coastal waters hold huge Posidonia beds, underwater meadows that harbor rare crustaceans , sponges and Ascidiacea (sea squirts). [ 3 ] As of 2009 the region was not sufficiently covered in the EuMon database.
Recruiting volunteers to monitor species may help address the issue. [ 7 ]
The Iberian Peninsula is particularly rich in species, including rare and endemic species, due to its complex climate and terrain, and because it provided refugia during the glacial period of the Pleistocene . [ 8 ] A 2011 study of spiders in the coastal dunes of Portugal showed that the primary factor in beta diversity was a broad-scale gradient of mediterraneity. [ 9 ] Diversity was lower in the northern dunes, which are in the Eurosiberian biogeographic region, and higher in the center and south in the Mediterranean biogeographic region [ 10 ] [ a ]
Arco Aguilar and Rodríguez Delgado state that three large floristic regions originated in the Mesogean region after the Pleistocene glaciation, the Mediterranean, Saharo-North-Arabian and Iranian-Turanian. [ 12 ] [ b ] Academics such as Ana Isabel Queiroz and Simon Pooley consider that the Mediterranean biogeographic region includes all of the Mediterranean Sea and all the lands surrounding it that have a Mediterranean-type climate (MTC). [ 14 ]
The Mediterranean Basin is about 3,800 kilometres (2,400 mi) long, from Lebanon in the east to Portugal in the west, and about 1,000 kilometres (620 mi) wide, from Morocco and Libya in the south to Italy in the north. [ 1 ] The region contains about 1.6% of the world's dry land but has about 10% of the known vascular plant species, with over 25,000 identified to date.
More than half of them are endemic. [ 15 ]
The biogeographic origins of the non-indigenous plants of the region include northern and central Eurasia, southwest and central Asia, North Africa, Arabia and the tropics of Africa.
For example, the Mediterranean species of the Androcymbium genus migrated northward from tropical Africa via the Eastern African mountain ranges to reach the Mediterranean in the Middle Miocene , at a time when the climate was quite different from today. [ 16 ] Molecular phylogeography is starting to give new insights into the origins and evolution of Mediterranean species. [ 17 ]
An analysis of literature has found about 17,000 marine species recorded as occurring in the Mediterranean Sea.
This estimate is probably low, with microbes significantly under-reported, and with large gaps in knowledge of the deep sea areas and the southern and eastern part of the sea.
Biodiversity is generally greater in the coastal and shallow regions, lower in deeper areas.
The ecology is threatened by habitat loss or degradation from fishing, pollution, climate change, eutrophication and alien species. [ 18 ] | https://en.wikipedia.org/wiki/Mediterranean_Biogeographic_Region |
Medivir is a Swedish biotech company. [ 1 ] Medivir focuses its research focus on oncology and particularly on innovative pharmaceuticals that meet substantial unmet medical needs. The pharmaceutical development work is conducted both in-house and through partnerships, usually with global pharmaceutical companies.
Medivir has a leading expertise in the design of protease inhibitors and in the science of nucleotides and nucleosides . [ 2 ] Medivir is listed on the Nasdaq Stockholm Mid Cap List.
In February 2020, Medivir announced that the company has signed a licensing agreement for Xerclear with Chinese company Shijiazhuang Yuanmai Biotechnology Co Ltd (SYB). The agreement gives SYB the right to register, manufacture and market the product in China. [ 3 ]
In 2016 Medivir announced that it would focus its research on cancers of high unmet medical need , where existing therapies are not very successful and there is a great opportunity to provide real benefit to patients who have few treatment options. Some cancer types of particular interest to Medivir include hepatocellular carcinoma (HCC), glioblastoma multiforme (GBM) and pancreatic cancer , which are all highly aggressive diseases with poor treatment options and very low overall survival rates on the best current treatments today. HCC is a liver cancer derived from hepatocyte cells. HCC is one of the most common cancers worldwide and late stage HCC has a mean overall survival of only 9–11 months on the best available treatment today. Medivir motivated the transition from its origin in retroviral drugs to oncology by it being a logical extension of their expertise in liver disease from earlier work on hepatitis C to this area.
This Swedish corporation or company article is a stub . You can help Wikipedia by expanding it . | https://en.wikipedia.org/wiki/Medivir |
Medlar bodies , also known as sclerotic or muriform cells , are thick-walled cells (5–12 microns) with multiple internal transverse septa or chambers that resemble copper pennies . When present in skin or subcutaneous tissue , the cells are indicative of chromoblastomycosis . [ 1 ] [ 2 ] [ 3 ]
This article related to pathology is a stub . You can help Wikipedia by expanding it . | https://en.wikipedia.org/wiki/Medlar_bodies |
The Medog Hydropower Station ( Chinese : 墨脱水电站 ) [ 1 ] or Motuo Hydropower Station [ 2 ] is a planned 60,000 megawatt (MW) hydroelectric dam project under development on the Yarlung Tsangpo river in Tibet Autonomous Region , China . Upon completion, it will become the world's largest hydropower facility , with an anticipated annual power generation capacity of 300 billion kilowatt-hours —triple that of the Three Gorges Dam . The Chinese government authorized the dam's construction in December 2024, with an estimated investment exceeding 1 trillion yuan (approximately US$ 137 billion). [ 3 ] The project is intended to be developed as a single-phase installation, with commercial operations planned for 2033. [ 4 ]
The facility is planned to be constructed in Medog County within the Nyingtri Prefecture , situated near the Indian border state of Arunachal Pradesh . The dam site is intended to be located along the lower sections of the Yarlung Tsangpo, which originates in western Tibet 's glacial regions. This watercourse continues into India as the Brahmaputra River and into Bangladesh as the Jamuna River , serving as a crucial water source for these regions. [ 3 ]
The Medog Hydropower Station represents part of China's broader hydroelectric development strategy in Tibet . Since 2000, China has initiated or proposed 193 hydropower projects in the region, with approximately 60% still in planning or preparatory phases. As of late 2024, while construction approval has been granted, specific details regarding the project's commencement and completion timeline remain unpublished. The Chinese government has not yet released comprehensive environmental impact assessments or detailed implementation plans for the project. [ 3 ]
The project is wholly owned and developed by Power Construction Corporation of China (PowerChina), a state-owned construction enterprise. Commercial operations were planned to begin in 2033. With a projected investment more than quadruple that of the Three Gorges Dam (which cost 250 billion yuan), the Medog Hydropower Station represents one of China's most ambitious infrastructure projects and one of the most expensive infrastructure projects in history. The facility's planned annual power output of 300 billion kilowatt-hours would establish it as the world's most productive hydroelectric installation, significantly surpassing current records. [ 3 ] [ 4 ]
The project intends to harness a 2,000 meter river elevation drop within a 50-kilometer stretch, granting it the ability to generate significant amounts of hydroelectric power. This section flows through the Yarlung Tsangpo Grand Canyon , recognized as Earth's deepest canyon system. The intended construction plan necessitates the excavation of four 20-kilometer tunnels through Namcha Barwa mountain to divert the Yarlung Tsangpo River. [ 5 ]
The project has faced resistance from various parties, which include environmental organizations , downstream nations, and Tibetan rights groups. Similar hydroelectric developments in Tibet have previously sparked protests, including recent demonstrations against the Kamtok Dam project on the Drichu/Yangtze River that led to over 1,000 arrests. India and Bangladesh have also voiced apprehension about the project's potential effects on their water resources. [ 3 ]
Tibetan rights organizations characterized the project as an example of resource exploitation at the expense of Buddhist cultural heritage and local communities. [ 5 ]
While specific displacement figures remain undisclosed, the project will necessitate population relocation in the affected area. For comparison, the Three Gorges Dam project resulted in approximately 1.4 million relocations, although the Medog region's lower population density suggests fewer displacements may be required. The development threatens to impact culturally significant sites in what Tibetans consider one of their most sacred regions. According to the International Campaign for Tibet , the 193 combined projects in the region could potentially displace over 1.2 million people and affect numerous religious sites if completed. [ 3 ]
Environmental organizations have identified several potential ecological consequences of the project. Many expressed concern about project's impact on the Tibetan Plateau's biodiversity. The region that will be impacted by the dam is recognized as one of Tibet's most ecologically diverse areas, leading to fears about ecosystem disruption. [ 5 ]
The dam's construction is expected to significantly alter downstream water flow patterns and impact local biodiversity . The project site's location in a seismically active zone prone to landslides has raised additional safety concerns, as the reservoir's water mass could potentially influence geological stability. [ 3 ] The steep, narrow topography of the gorge caused geological experts to warn about increased landslide risks. In 2022, engineers from the Sichuan provincial geological bureau specifically highlighted the dangers of "earthquake-induced landslides and mud-rock flows" as significant threats to the project's stability. [ 5 ]
Chinese state media has characterized the project as environmentally conscious , emphasizing its role in advancing Beijing's climate neutrality objectives while promoting regional economic development. Chinese officials maintained that the project will have minimal environmental impact, though specific impact assessments remain unpublished. [ 5 ]
The project has generated apprehension among downstream nations regarding water security. Hydrological experts have drawn parallels with China's previous dam projects on the Mekong River , where upstream water control has been associated with increased drought frequency and severity in downstream regions over the past twenty years. Critics noted that India and Bangladesh could face compromised water access, biodiversity disruption, and riverbank erosion akin to those faced by Thailand , Vietnam , and Cambodia from earlier Chinese hydroelectric projects. [ 3 ]
A 2020 analysis by the Lowy Institute indicated that China's control over Tibetan Plateau rivers could potentially provide significant geopolitical leverage over India's economy . [ 6 ] Indian authorities responded to the project by exploring countermeasures, including the potential development of their own large-scale hydroelectrical dam and reservoir system to mitigate the dam's impacts. The Chinese Ministry of Foreign Affairs asserted in 2020 that China maintains a "legitimate right" to dam the river, stating they have considered downstream effects in their planning. [ 5 ] | https://en.wikipedia.org/wiki/Medog_Hydropower_Station |
Medsafe , the New Zealand Medicines and Medical Devices Safety Authority , is the medical regulatory body run by the New Zealand Ministry of Health , administering the Medicines Act 1981 and Medicines Regulations 1984. [ 1 ]
Medsafe employs approximately 60 staff members in two offices. The head office, based in Wellington, New Zealand , handles "centralised administrative functions, product approval, and standard settings." The Investigation and Border Control operates out of the Auckland office. [ 1 ]
This article about an organisation in New Zealand is a stub . You can help Wikipedia by expanding it . | https://en.wikipedia.org/wiki/Medsafe |
The medulla is a horizontal layer within a lichen thallus . It is a loosely arranged layer of interlaced hyphae below the upper cortex and photobiont zone, but above the lower cortex. [ 1 ] The medulla generally has a cottony appearance. It is the widest layer of a heteromerous lichen thallus.
This article about lichens or lichenology is a stub . You can help Wikipedia by expanding it . | https://en.wikipedia.org/wiki/Medulla_(lichenology) |
Medullary thymic epithelial cells ( mTECs ) represent a unique stromal cell population of the thymus which plays an essential role in the establishment of central tolerance . Therefore, mTECs rank among cells relevant for the development of functional mammal immune system .
T cell precursors rise in bone marrow and migrate through the bloodstream to the thymus for further development. During their maturation in the thymus, they undergo a process called V(D)J recombination which conducts the development of T cell receptors (TCRs). The mechanism of this stochastic process enables on one hand the generation of vast repertoire of TCRs, however, on the other hand causes also origin of so called "autoreactive T cells" which recognize self antigens via their TCRs. Autoreactive T cells must be eliminated from the body or skewed into the T Regulatory cells (TRegs) lineage to prevent manifestations of autoimmunity . mTECs possess the ability to deal with these autoreactive clones via mediation of the processes of central tolerance, namely clonal deletion or T regulatory cells selection , respectively.
N.B.: All the below cited references utilized mouse as a model organism .
In 1989, two scientific groups came up with the hypothesis that the thymus expresses genes which are in the periphery, strictly expressed by specific tissues ( e.g.: Insulin produced by β cells of the pancreas ) to subsequently present these so-called " tissue-restricted antigens " (TRAs) from almost all parts of the body to developing T cells in order to test which TCRs recognize self-tissues and can be therefore harmful to the body. [ 1 ] It was found, after more than a decade, that this phenomenon is managed specifically by mTECs in the thymus and was named Promiscuous gene expression (PGE). [ 2 ]
Aire is a protein called autoimmune regulator (Aire) which is also specifically expressed by mTECs. [ 3 ] and its expression is completely dependent on NF- kappa B signaling pathway . [ 4 ] Aire recognizes target genes of TRAs via specific methylation marks [ 5 ] [ 6 ] and requires about 50 partner molecules for activation of their expression. [ 7 ] Moreover, Aire-dependent activation of TRA genes expression is accompanied by formation of DNA double-strand breaks. [ 8 ] which probably results in very short lifespan of mTECs between 2–3 days [ 9 ]
Mutations of Aire gene in human cause a rare autoimmune disorder called Autoimmune Polyendocrinopathy Candidiasis Ectodermal Distrophy (APECED)., [ 10 ] [ 11 ] which usually manifests in combination with other autoimmune diseases e.g.: diabetes mellitus type 1 . Dysfunction of murine Aire gene results in comparable scenario and therefore mouse is used as the model organism for investigation of APECED.
mTECs as a population are capable to express more than 19000 genes (about 80% of mouse genome) among which approximately 4000 belong to Aire-dependent TRAs. It is important to emphasize that single mTEC expresses about 150 Aire-dependent TRAs and approximately 600 Aire-independent TRAs, [ 12 ] indicating that other still unknown PGE regulators exist. Indeed, another protein called Fezf2 was suggested to be the second regulator of PGE. [ 13 ]
It was shown that each mTEC expresses stochastically 1-3% of TRA pool. [ 14 ] However, more recent studies discovered stable co-expression patterns between TRA genes which are localized in close proximity, suggesting "order in this stochastic process". [ 15 ] [ 16 ]
T cell precursors extravasate from the bloodstream in cortico-medullary junction and they first migrate to the thymic cortex, where they undergo construction of TCRs and subsequently a process called T cell positive selection which is mediated by mTEC-related cells: cortical thymic epithelial cells (cTECs). This process verifies, whether newly generated TCRs are functional. [ 17 ] About 90% of T cells displays badly rearranged TCRs, they cannot reach the positive selection and they die by neglect in the cortex. [ 18 ] The rest starts to express CCR7, which is a receptor for mTEC-generated chemokine CCL21, and migrate after concentration gradient to the thymic medulla to encounter mTECs. [ 19 ]
mTECs are not only mediators of PGE and "factories of TRAs". They also express high levels of MHC II and costimulatory molecules CD80/CD86 and rank among efficient antigen-presenting cells (APCs). [ 2 ] Moreover, they utilize macroautophagy to load self antigens on MHCII molecules. [ 20 ] Thus, mTECs are capable to present self-generated TRAs on their MHC molecules to select potential autoreactive T cells. It was published that mTECs mediate clonal deletion ( recessive tolerance ), via presentation of TRAs, which leads to the apoptosis of autoreactive T cells, [ 21 ] [ 22 ] [ 23 ] as well as they are competent to skew autoreactive T cells into TRegs, also through the presentation of TRAs, which then migrate to the periphery to protect tissues against autoreactive T cells that occasionally avoid selection processes in the thymus ( dominant tolerance ). [ 24 ] [ 25 ]
How mTECs discriminate between these two modes of tolerance? It was shown that prospective TRegs interact with presented TRAs with lower affinity than those which are clonally deleted. [ 17 ] Furthermore, it was also revealed that specific TRAs skew autoreactive T cells into TRegs with much higher efficiency than they do in the case of clonal deletion. [ 26 ]
mTECs form rare population which is composed of approximately 100000 cells per thymus of 2-week-old mice. [ 27 ] Thus, there is low probability of encounter between autoreactive T cell and mTEC. Unidirectional antigen transfer from mTECs to thymic dendritic cells (DCs), which itself can't express TRAs, extends the network of TRA presentation, enables TRA processing by different microenvironments and increases the probability of encounter between autoreactive T cell and its appropriate self-antigen. [ 28 ] [ 29 ] [ 30 ] Moreover, DCs competently induce both recessive and dominant tolerance as well as mTECs. [ 29 ]
In contrast, another seminal study reveals that mTECs itself suffice to establish both recessive and dominant tolerance without help of additional APCs. [ 31 ]
mTEC population is not homogenous and basically could be subdivided into more numerous population of mTECs which express low number of MHCII and CD80/CD86, namely mTECs Lo and smaller population of mTECs Hi which express higher amounts of these molecules. [ 32 ] PGE regulator Aire is expressed only by part of mTECs Hi . [ 9 ] However, this claim does not mean that mTECs Lo don't contribute to PGE, mTECs Hi , especially that expressing Aire, are just much more efficient in this process. [ 32 ]
There is evidence that mTECs Lo serve as precursors of mTECs Hi in the embryonic thymus [ 33 ] [ 34 ] Nevertheless, situation changes after birth, where only part of mTECs Lo pool represents immature mTECs Hi reservoir [ 33 ] and another part is constituted by mature mTECs which are specialized for expression of chemokine CCL21, [ 35 ] discussed above. Further subset of mTECs Lo pool is formed by terminally differentiated cells called Post- Aire mTECs which already downregulated the expression of Aire, MHCII and CD80/CD86. [ 36 ]
mTECs can develop into Thymic mimetic cells , which combine the mTEC identity with lineage specific transcription factors. These cells exhibit the phenotype of differentiated peripheral cells and produce their corresponding TRAs. The most famous example is Hassall's corpuscles . [ 37 ]
TECs (mTECs and cTECs) originate from the third pharyngeal pouch which is a product of endoderm . [ 38 ] Their common origin points to the fact that both mTECs and cTECs rise from one bipotent progenitor . This notion was confirmed by several studies of embryonic thymus. [ 39 ] [ 40 ] and was further developed by finding that these bipotent progenitors express cTEC markers. [ 41 ] [ 42 ] Nevertheless, another sources document existence of mTEC unipotent progenitors that express claudin 3 and 4 (Cld3/4). [ 43 ] [ 44 ] These two opposite findings were interfaced by observation of unipotent mTEC progenitors in the postnatal thymus that previously expressed cTEC markers and concurrently express Cld3/4. [ 45 ] On the other hand, several other studies describe appearance of bipotent progenitors in postnatal thymus. [ 46 ] [ 47 ] [ 48 ] [ 49 ] Thus, embryonic as well as postnatal thymus might shelter both bipotent TEC or unipotent mTEC progenitors.
Similarly to Aire expression, mTECs development is highly dependent on NF- kappa B signaling pathway. [ 50 ] | https://en.wikipedia.org/wiki/Medullary_thymic_epithelial_cells |
Meera Nanda (born 1954) is an Indian writer and historian of science , [ 1 ] who has authored several works critiquing the influence of Hindutva , postcolonialism and postmodernism on science, and the flourishing of pseudoscience and vedic science . Meera Nanda taught History of Science at the Indian Institute of Science Education and Research (IISER) Mohali from 2009 to 2017, [ 2 ] and later - from 2019 to 2020 - she was a Guest Faculty in Humanities and Social Sciences at IISER Pune . [ 3 ] [ 4 ] In 2023 she became a fellow with the Committee for Skeptical Inquiry . [ 5 ]
Nanda was educated in science and philosophy with a PhD in biotechnology from the Indian Institute of Technology, Delhi , and a PhD in science studies from Rensselaer Polytechnic Institute . [ 6 ] [ 7 ]
She was a John Templeton Foundation Fellow in Religion and Science (2005–2007). [ 1 ] [ 8 ] In January 2009, she was a Fellow at the Jawaharlal Nehru Institute for Advanced Study, in the Jawaharlal Nehru University for research in Science, Post-Modernism and Culture. [ 9 ] She was also a visiting faculty of history and philosophy of science at Indian Institute of Science Education and Research, Mohali from 2009 to 15 May 2017. She was a visiting faculty member of the department of Humanities and Social Sciences, IISER Pune [ 10 ] in 2019 and 2020.
Nanda has authored several works on religion, most notably Prophets Facing Backward: Postmodern Critiques of Science and Hindu Nationalism in India (2004), [ 11 ] and her 2009 book The God Market which examined how India is experiencing a rising tide of popular Hinduism, including government financing of Hinduism despite the nation's secular characteristic. The book was reviewed by William Dalrymple in Outlook Magazine . [ 12 ] [ 13 ] | https://en.wikipedia.org/wiki/Meera_Nanda |
The Meerwein arylation is an organic reaction involving the addition of an aryl diazonium salt (ArN 2 X) to an electron-poor alkene usually supported by a metal salt. [ 1 ] The reaction product is an alkylated arene compound. The reaction is named after Hans Meerwein , one of its inventors who first published it in 1939.
An electron-withdrawing group (EWG) on the alkene makes it electron deficient and although the reaction mechanism is unclear, [ 2 ] involvement of an aryl radical is presumed after loss of nitrogen in the diazonium salt followed by a free radical addition . In the primary reaction product the intermediate alkyl radical is then captured by the diazonium counterion X which is usually a halogen or a tetrafluoroborate . In a subsequent step an elimination reaction liberates HX (for instance hydrochloric acid ) and an aryl vinyl compound is formed. The reaction mechanism from the arene's view ranks as a radical-nucleophilic aromatic substitution .
In a general scope a Meerwein arylation is any reaction between an aryl radical and an alkene. [ 3 ] The initial intermediate is an aryl enthenyl radical which can react with many trapping reagents such as hydrogen or halogens or with those based on nitrogen or sulfur .
A reported reaction of alkene acrylic acid with an aryl diazonium salt and copper(I) bromide and hydrobromic acid yields the α-bromocarboxylic acid. [ 4 ] When the alkene is butadiene the initial reaction product with catalyst copper(II) chloride is a 4-chloro-2-butene and after an elimination the aryl substituted butadiene. [ 5 ] In a so-called reductive arylation with 3-buten-2-one, titanium trichloride reduces the newly formed double bond. [ 6 ]
In a novel kilogram-scale metal-free Meerwein arylation the diazonium salt is formed from 2-nitroaniline, the alkene isopropenyl acetate is an adduct of propyne and acetic acid and the reaction product 2-nitrophenylacetone: [ 7 ] | https://en.wikipedia.org/wiki/Meerwein_arylation |
The Meerwein–Ponndorf–Verley (MPV) reduction in organic chemistry is the reduction of ketones and aldehydes to their corresponding alcohols utilizing aluminium alkoxide catalysis in the presence of a sacrificial alcohol. [ 1 ] The advantages of the MPV reduction lie in its high chemoselectivity and its use of a cheap environmentally friendly metal catalyst. MPV reductions have been described as "obsolete" owing to the development of sodium borohydride and related reagents. [ 2 ]
The MPV reduction was independently discovered by Albert Verley and the team of Hans Meerwein and Rudolf Schmidt in 1925. They found that a mixture of aluminium ethoxide and ethanol could reduce aldehydes to their alcohols. [ 3 ] [ 4 ] Ponndorf applied the reaction to ketones and upgraded the catalyst to aluminium isopropoxide in isopropanol . [ 5 ]
The MPV reduction is believed to go through a catalytic cycle involving a six-member ring transition state as shown in Figure 2. Starting with the aluminium alkoxide 1 , a carbonyl oxygen is coordinated to achieve the tetra coordinated aluminium intermediate 2 . Between intermediates 2 and 3 the hydride is transferred to the carbonyl from the alkoxy ligand via a pericyclic mechanism . At this point the new carbonyl dissociates and gives the tricoordinated aluminium species 4 . Finally, an alcohol from solution displaces the newly reduced carbonyl to regenerate the catalyst 1 .
Each step in the cycle is reversible. The reaction is driven by the thermodynamic properties of the intermediates and the products. Several other mechanisms have been proposed for this reaction, including a radical mechanism as well as a mechanism involving an aluminium hydride species. The commonly accepted direct hydride transfer is supported by experimental and theoretical data. [ 6 ]
One of the great draws of the Meerwein–Ponndorf–Verley reduction is its chemoselectivity . Aldehydes are reduced before ketones allowing for a measure of control over the reaction. If it is necessary to reduce one carbonyl in the presence of another, the common carbonyl protecting groups may be employed. Groups, such as alkenes and alkynes, that normally pose a problem for reduction by other means have no reactivity under these conditions. [ 7 ]
The aluminium based Meerwein–Ponndorf–Verley reduction can be performed on prochiral ketones leading to chiral alcohols. The three main ways to achieve the asymmetric reduction is by use of a chiral alcohol hydride source, use of an intramolecular MPV reduction, or use of a chiral ligand on the aluminium alkoxide.
One method of achieving the asymmetric MPV reduction is with the use of chiral hydride donating alcohols. The use of chiral alcohol (R)-(+)- sec - o -bromophen-ethyl alcohol gave 82%ee (percent enantiomeric excess ) in the reduction of 2-chloroacetophenone. [ 8 ] This enantioselection is due to the sterics of the two phenol groups in the six membered transition state as shown in Figure 3. In Figure 3, 1 is favored over 2 due to the large steric effect in 2 from the two phenyl groups.
The use of an intramolecular MPV reduction can give good enantiopurity. [ 9 ] By tethering the ketone to the hydride source only one transition state is possible (Figure 4) leading to the asymmetric reduction. This method, however, has the ability to undergo the reverse Oppenauer oxidation due to the proximity of the two reagents. Thus the reaction runs under thermodynamic equilibrium with the ratio of the products related to their relative stabilities. After the reaction is run the hydride-source portion of the molecule can be removed.
Chiral ligands on the aluminium alkoxide can affect the stereochemical outcome of the MPV reduction. This method lead to the reduction of substituted acetophenones in up to 83%ee [ 10 ] (Figure 5). The appeal of this method is that it uses a chiral ligand as opposed to a stoichiometric source of chirality. The low selectivity of this method is attributed to the shape of the transition state. It has been shown that the transition state is a planar six member transition state. This is different than the believed Zimmerman-Traxler model like transition state. [ 6 ]
Several problems restrict the use of the Meerwein–Ponndorf–Verley reduction compared to the use of other reducing agents. The stereochemical control is seriously limited. Often a large amount of aluminium alkoxide is needed when using commercial reagent, and there are several known side reactions.
While commercial aluminium isopropoxide is available, the use of it often requires catalyst loadings of up to 100-200 mol%. This hinders the use of the MPV reduction on scale. Aluminium alkoxides made in situ from trimethyl aluminium reagents have far better activity requiring as little as 10% loading. The activity difference is believed to be due to the large aggregation state of the commercially available product. [ 11 ]
Several side reactions are known to occur. In the case of ketones and especially aldehydes aldol condensations have been observed. Aldehydes with no α-hydrogens can undergo the Tishchenko reaction . [ 7 ] Finally, in some cases the alcohol generated by the reduction can be dehydrated giving an alkyl carbon.
The Meerwein–Ponndorf–Verley reduction has been used in the synthesis of chiral amines from ketimines using a chiral alkoxide. The addition of a phosphinoyl group to the nitrogen of the ketimine allowed for high enantioselectivity up to 98%ee. [ 12 ]
Work has been done in the use of lanthanides and transition metals for the Meerwein–Ponndorf–Verley reduction. Both ruthenium and samarium have shown high yields and high stereoselectivity in the reduction of carbonyls to alcohols. [ 13 ] [ 14 ] The ruthenium catalyst has been shown, however, to go through a ruthenium hydride intermediate. The Meerwein–Ponndorf–Verley reduction has also been effected with synthetically useful yield by plutonium (III) isopropoxide. [ 15 ]
The standard MPV reduction is a homogeneous reaction several heterogeneous reactions have been developed. [ 16 ] | https://en.wikipedia.org/wiki/Meerwein–Ponndorf–Verley_reduction |
Mefloquine , sold under the brand name Lariam among others, is a medication used to prevent or treat malaria . [ 4 ] When used for prevention it is typically started before potential exposure and continued for several weeks after potential exposure. [ 4 ] It can be used to treat mild or moderate malaria but is not recommended for severe malaria. [ 4 ] It is taken by mouth . [ 4 ]
Common side effects include vomiting, diarrhea, headaches, sleep disorders, and a rash. [ 4 ] Serious side effects include potentially long-term mental health problems such as depression , hallucinations , and anxiety and neurological side effects such as poor balance , seizures , and ringing in the ears . [ 4 ] It is therefore not recommended in people with a history of mental health problems or epilepsy . [ 4 ] It appears to be safe during pregnancy and breastfeeding . [ 1 ]
Mefloquine was developed by the United States Army in the 1970s and came into use in the mid-1980s. [ 5 ] [ 6 ] [ 7 ] It is on the World Health Organization's List of Essential Medicines . [ 8 ] [ 9 ] It is available as a generic medication . [ 4 ]
Mefloquine is used to both prevent and treat certain forms of malaria. [ 10 ]
Mefloquine is useful for the prevention of malaria in all areas except for those where parasites may have resistance to multiple medications, [ 11 ] and is one of several anti-malarial medications recommended by the United States Centers for Disease Control and Prevention for this purpose. It is also recommended by the Infectious Disease Society of America for malaria prophylaxis as a first or second-line agent, depending on resistance patterns in the malaria found in the geographic region visited. [ 12 ] [ 13 ] It is typically taken for one to two weeks before entering an area with malaria. [ 10 ] Doxycycline and atovaquone/proguanil provide protection within one to two days and may be better tolerated. [ 14 ] [ 15 ] If a person becomes ill with malaria despite prophylaxis with mefloquine, the use of halofantrine and quinine for treatment may be ineffective. [ 16 ] : 4
Mefloquine is used as a treatment for chloroquine -sensitive or resistant Plasmodium falciparum malaria, and is deemed a reasonable alternative for uncomplicated chloroquine-resistant Plasmodium vivax malaria. [ 10 ] [ 16 ] It is one of several drugs recommended by the United States' Centers for Disease Control and Prevention. [ 17 ] It is not recommended for severe malaria infections, particularly infections from P. falciparum , which should be treated with intravenous antimalarials . [ 10 ] [ 16 ] Mefloquine does not eliminate parasites in the liver phase of the disease, and people with P. vivax malaria should be treated with a second drug that is effective for the liver phase, such as primaquine . [ 16 ] : 4
Resistance to mefloquine is common around the west border in Cambodia and other parts of Southeast Asia. [ 18 ] The mechanism of resistance is by increase in Pfmdr1 copy number. [ 19 ]
Mefloquine is contraindicated in those with a previous history of seizures or a recent history of psychiatric disorders. [ 10 ]
Available data suggests that mefloquine is safe and effective for use by pregnant women during all trimesters of pregnancy, [ 20 ] and it is widely used for this indication. [ 21 ] In pregnant women, mefloquine appears to pose minimal risk to the fetus, [ 21 ] [ 22 ] and is not associated with increased risk of birth defects or miscarriages. [ 23 ] Compared to other malaria chemoprophylaxis regimens, however, mefloqinone may produce more side effects in non-pregnant travelers.
Mefloquine is also safe and effective for use during breastfeeding, [ 20 ] though it appears in breast milk in low concentrations. [ 11 ] [ 16 ] : 9 The World Health Organization (WHO) gives approval for the use of mefloquine in the second and third trimesters of pregnancy and use in the first trimester does not mandate termination of pregnancy. [ 11 ]
Common side effects include vomiting, diarrhea, headaches, and a rash. [ 4 ] Severe side effects requiring hospitalization are rare, [ 11 ] but include mental health problems such as depression , hallucinations , anxiety and neurological side effects such as poor balance , seizures , and ringing in the ears . [ 4 ] Mefloquine is therefore not recommended in people with a history of psychiatric disorders or epilepsy . [ 4 ]
Liver function tests should be performed during long-term administration of mefloquine. [ 24 ] Alcohol use should be avoided during treatment with mefloquine. [ 25 ]
In 2013, the U.S. Food and Drug Administration (FDA) added a boxed warning to the prescription label of mefloquine regarding the potential for neuropsychiatric side effects that may persist even after discontinuing administration of the medication. [ 26 ] [ 27 ] In 2013 the FDA stated "Neurologic side effects can occur at any time during drug use, and can last for months to years after the drug is stopped or can be permanent." [ 28 ] Neurologic effects include dizziness , loss of balance, seizures , and tinnitus . Psychiatric effects include nightmares , visual hallucinations , auditory hallucinations , anxiety , depression , unusual behavior, and suicidal ideations .
Central nervous system events requiring hospitalization occur in about one in 10,000 people taking mefloquine for malaria prevention, with milder events (e.g., dizziness, headache, insomnia , and vivid dreams) in up to 25%. [ 29 ] When some measure of subjective severity is applied to the rating of adverse events, about 11–17% of travelers are incapacitated to some degree. [ 14 ]
Mefloquine may cause abnormalities with heart rhythms that are visible on electrocardiograms . Combining mefloquine with other drugs that cause similar effects, such as quinine or quinidine , can increase these effects. Combining mefloquine with halofantrine can cause significant increases in QTc intervals . [ 16 ] : 10
The mechanism of action of mefloquine is unclear and several competing hypotheses exist. [ 30 ]
Mefloquine has known off-target activities . [ 31 ] [ 32 ] This includes affinity for the serotonin 5-HT 2A receptor and to a lesser extent for the serotonin 5-HT 2C receptor , but not for the serotonin 5-HT 1A receptor . [ 31 ] [ 32 ] Mefloquine acts as a partial agonist of both the serotonin 5-HT 2A and 5-HT 2C receptors, similarly to serotonergic psychedelics like LSD , DOM , and DMT . [ 31 ] [ 32 ] It also binds to the serotonin transporter and acts as a serotonin reuptake inhibitor , acts as a serotonin 5-HT 3 receptor antagonist , and shows affinity for the dopamine D 3 receptor , among other actions. [ 31 ] [ 32 ] [ 33 ] [ 34 ] These properties of mefloquine, especially serotonin 5-HT 2A receptor agonism, may be involved in the neurological and psychiatric adverse effects such as visual hallucinations that have been reported with its use particularly at high doses. [ 31 ] [ 32 ] Mefloquine is a drug that is thought to have potential antiepilectic effects due to its ability to non-specifically block connexin hemi-channels and pannexons. [ 35 ] [ 36 ]
Mefloquine is metabolized primarily through the liver . Its elimination in persons with impaired liver function may be prolonged, resulting in higher plasma levels and an increased risk of adverse reactions . The mean plasma elimination half-life of mefloquine is between 2 and 4 weeks. Total clearance is through the liver, and the primary means of excretion is through the bile and feces , as opposed to only 4% to 9% excreted through the urine . During long-term use, the plasma half-life remains unchanged. [ 37 ] [ 38 ]
Mefloquine is a chiral molecule with two asymmetric carbon centres, which means it has four different stereoisomers . The drug is currently manufactured and sold as a racemate of the ( R , S )- and ( S , R )-enantiomers by Hoffmann-La Roche , a Swiss pharmaceutical company. Essentially, it is two drugs in one. Plasma concentrations of the (–)-enantiomer are significantly higher than those for the (+)-enantiomer, and the pharmacokinetics between the two enantiomers are significantly different. The (+)-enantiomer has a shorter half-life than the (–)-enantiomer. [ 14 ] Specifically it is used as mefloquine hydrochloride.
The chemical structure of mefloquine is similar to that of tryptamine and its derivatives . [ 39 ] However, whereas tryptamine is an indolylethylamine, mefloquine is a quinolinylethylamine. [ 39 ] Mefloquine's structure is also particularly similar to that of 10,11-secoergoline (α, N -tetramethylenetryptamine). [ 39 ]
Mefloquine was formulated at Walter Reed Army Institute of Research (WRAIR) in the 1970s shortly after the end of the Vietnam war. Mefloquine was number 142,490 of a total of 250,000 antimalarial compounds screened during the study. [ 5 ]
Mefloquine was the first Public-Private Venture (PPV) between the US Department of Defense and a pharmaceutical company. WRAIR transferred all its phase I and phase II clinical trial data to Hoffman-LaRoche and Smith Kline . FDA approval as a treatment for malaria was swift. Most notably, phase III safety and tolerability trials were skipped. [ 5 ]
The drug was first approved in Switzerland in 1984 by Hoffmann-LaRoche, [ 40 ] who brought it to market with the name Lariam . [ 41 ]
However, mefloquine was not approved by the FDA for prophylactic use until 1989. This approval was based primarily on compliance, while safety and tolerability were overlooked. [ 5 ] Because of the drug's very long half-life, the Centers for Disease Control originally recommended a mefloquine dosage of 250 mg every two weeks; however, this caused an unacceptably high malaria rate in the Peace Corps volunteers who participated in the approval study, so the drug regimen was switched to once a week. [ 14 ]
By 1991, Hoffman was marketing the drug on a worldwide basis. [ 41 ]
By the 1992 UNITAF , Canadian soldiers were being prescribed the drug en masse . [ 42 ]
By 1994, medical professionals were noting "severe psychiatric side effects observed during prophylaxis and treatment with mefloquine", and recommending that "the absence of contraindications and minor side effects during an initial course of mefloquine should be confirmed before another course is prescribed." [ 43 ] Other doctors at the University Hospital of Zurich noted in a case of "a 47-year-old, previously healthy Japanese tourist" who had severe neuropsychiatric side-effects from the drug that [ 44 ]
The neuropsychiatric side effects of the antimalarial drug mefloquine are well documented. They include anxiety, depression, hallucinations, acute psychosis, and seizures. The incidence of these side effects is 1 in 13,000 with prophylactic use and 1 in 250 with therapeutic use.
The first randomized, controlled trial on a mixed population was performed in 2001. Prophylaxis with mefloquine was compared to prophylaxis with atovaquone-proguanil . Roughly 67% of participants in the mefloquine arm reported greater than or equal to one adverse event, versus 71% in the atovaquone-proguanil arm. In the mefloquine arm, 5% of the users reported severe events requiring medical attention, versus 1.2% in the atovaquone-proguanil arm. [ 5 ] [ 45 ]
In August 2009, Roche stopped marketing Lariam in the United States. [ 46 ]
Retired soldier Johnny Mercer , who was later appointed Minister for Veterans Affairs by Boris Johnson , told in 2015 that he had received "a letter about once or twice a week" about ill-effects from the drug. [ 47 ] In July 2016, Roche took this brand off the market in Ireland. [ 46 ]
In 2006, the Australian military deemed mefloquine "a third-line drug" alternative, and over the five years from 2011 only 25 soldiers had been prescribed the drug, and only in cases of their intolerance for other alternatives. [ 46 ] Between 2001 and 2012, 16,000 Canadian soldiers sent to Afghanistan were given the drug as a preventative measure. [ 46 ] In 2013, the US Army banned mefloquine from use by its special forces such as the Green Berets . [ 46 ] In autumn 2016, the UK military followed suit with their Australian peers after a parliamentary inquiry into the matter revealed that it can cause permanent side effects and brain damage. [ 46 ]
In early December 2016, the German defence ministry removed mefloquine from the list of medications it would provide to its soldiers. [ 46 ]
In autumn 2016, Canadian Surgeon General Brigadier General Hugh Colin MacKay told a parliamentary committee that faulty science supported the assertion that the drug has indelible noxious side effects. An expert from Health Canada named Barbara Raymond told the same committee that the evidence she had read failed to support the conclusion of indelible side effects. [ 46 ] Canadian soldiers who took mefloquine when deployed overseas have claimed they have been left with ongoing mental health problems. [ 48 ]
In 2020 the UK Ministry of Defence (MoD) admitted to a breach of duty regarding the use of Mefloquine. [ 49 ] by acknowledging numerous instances of failure to assess the risks and warn of potential side effects of the drug.
In June 2010, the first case report appeared of a progressive multifocal leukoencephalopathy being successfully treated with mefloquine. Mefloquine can also act against the JC virus . Administration of mefloquine seemed to eliminate the virus from the patient's body and prevented further neurological deterioration. [ 50 ]
Mefloquine alters cholinergic synaptic transmission through both postsynaptic [ 51 ] and presynaptic actions. [ 52 ] The postsynaptic action to inhibit acetylcholinesterase changes transmission across synapses in the brain. [ 53 ] | https://en.wikipedia.org/wiki/Mefloquine |
MegaTransect was the name for a project conducted in Africa in 1999 by J. Michael Fay to spend 465 days on the expedition hike of 2,000 miles (3,219 kilometers) across the Congo Basin of Africa to survey the ecological and environmental status of the region.
A transect is a term in ecology that denotes a survey of the natural vegetation through a particular area. The concept of a megatransect was conceived as a vegetation transect on a large scale that could be used to take an ecological census of the natural vegetation and ecosystems.
Shortly after the hike, Fay successfully lobbied alongside the President of Gabon to create 13 new national parks . In 2002, US Secretary of State Colin Powell and other Bush administration members gave 53 million dollars to help preserve the Congo Basin. [ citation needed ]
Mike Fay later went on to carry out the MegaFlyover in 2004.
Also in 2004, an international team conducted a "Megatransect" of the island of Madagascar . Dubbed "Hike Madagascar", the journey covered the entire island. Members met with rural farmers to help them improve their agricultural techniques and discuss their impact on the environment.
One of the first megatransects in the United States was conducted by Dr. Robert R. Humphrey when he rephotographed 535 miles of the natural vegetation along with the United States and Mexico border at the 1890s permanent border monument locations, each spaced about five miles apart, and published this work in 90 Years and 535 Miles: Vegetation Changes Along the Mexican Border (1987, pub. Univ. of NM Press, 448 pages).
In 1997 Craig C. Dremann conducted a megatransect surveying over 3,000 miles and at each mile-marker, noting the roadside vegetation, the perennial native grass , and exotic grass status throughout the Great Basin ecosystem. The route was from Reno, Nevada eastward to Hot Springs, South Dakota , and from South Dakota through Wyoming, Idaho, Nevada, and California, returning westward to Bishop, California , and then north back to Reno. [ citation needed ]
In 2005, Dremann conducted another vegetation megatransect, this time of the California portion of the Mojave desert , mapping over 1,000 miles on a mile-by-mile basis, for a fast-spreading exotic mustard species, Brassica tournefortii , noting the locations and density of the Mojave desert Mustard infestation in California . [ citation needed ]
Dremann suggests that a method of remotely conducting a large-scale vegetation megatransect is with photographs. Photographs that have been taken at ground-level at intervals from known locations can be stitched together to create large-scale to Continent-scale megatransect pictures of ecosystems.
In 2006, Dr. Michael C. McGrann and his wife Amy M. McGrann hiked the length of the California section of Pacific Crest National Scenic Trail (PCT) in the western United States from Mexico to the Oregon border (2,736 km) while systematically collecting avian-habitat data on 3,578 survey plots separated by 10-minute hiking intervals. This work was completed in a single field season from 2 April to 8 September. From this data, Dr. McGrann and his collaborators described the elevation and latitudinal distributions of birds along the PCT [ 1 ] and statistically modeled avian species richness relationships with elevation, climate, and environmental factors including temperature, precipitation, and primary productivity. [ 2 ] The results from this work showed that birds can exhibit heterogeneous relationships to temperature, precipitation, and productivity depending on the distinct environmental and climate conditions of each of the ecological regions traversed by the PCT. [ 3 ] The PCT megatransect is an ongoing research project for Dr. McGrann in collaboration with several other researchers. He has continued his biodiversity surveys along sections of the PCT in 2007, 2010, and 2015, and he is working both to expand taxa surveyed along the PCT and to involve his undergraduate students at William Jessup University in the PCT Mega-Transect .
In 2007–2008 J. Michael Fay and Lindsey Holm completed a 1300-mile Redwood Transect of 333 days. This was a megatransect that spanned from the southernmost to the northernmost redwood trees in California and Oregon. They walked extensively on private timberland and public land recording data on historical exploitation, current forest stand characteristics, silviculture, and many other aspects of the redwood ecosystem. The results will be published in National Geographic in 2009. [ citation needed ]
The Appalachian Trail Conservancy and the National Park Service are adopting the idea of a megatransect for the Appalachian Trail (A.T.) Like other megatransects, the A.T. MEGA-Transect aims to monitor the natural resources along the trail, understand the status and trends of these resources, and inform and engage the public and stakeholders. The 2,178-mile-long trail crosses 14 states, from Georgia to Maine, and is visited by one to two million people and completed by about 400 people each year. Volunteer citizen scientists are beginning to implement monitoring protocols to track natural resources such as wildlife presence, water quality, forest health, invasive plants, endangered species, mountain birds, phenology, and air quality. Professional scientists are also using the transect for independent research. The A.T. is oriented along the predicted migratory direction of species responding to climate change, making it a particularly important megatransect to establish and maintain.
For a rapidly changing planet, megatransects establish baseline data from which to draw future trends, and they can focus attention on particular ecosystems which are disappearing faster than others.
Establishing standard megatransects on specific regions or through various ecosystems of each continent, and periodic re–measurement of the ecological conditions along routes, every five to ten years, would provide very valuable measured data on environmental trends. | https://en.wikipedia.org/wiki/MegaTransect |
The Mega Borg oil spill occurred in the Gulf of Mexico on June 8, 1990, roughly 50 miles off the coast of Texas , when the oil tanker Mega Borg caught on fire and exploded. The cleanup was one of the first practical uses of bioremediation .
At 11:30 PM on the evening of Friday June 8, 1990, [ 1 ] an explosion in the cargo room of the Norwegian oil tanker the Mega Borg “ruptured the bulkhead between the pump room and the engine room”, [ 1 ] causing the ship to catch fire and begin to leak oil. [ 2 ] The 853-foot-long, 15-year-old vessel was about 50 miles off the coast of Galveston, Texas when the explosion occurred. [ 3 ] The weather at the time was calm and the tanker had easily passed Coast Guard safety inspections in April earlier that year. [ 3 ] While the direct cause of the engine room explosion remains unknown, the initial blast occurred during a lightering process in which the Mega Borg was transferring oil onto a smaller Italian tanker, the Fraqmura , in order to then transport the oil to Houston . [ 2 ] This transfer was necessary, as the Mega Borg was too large to dock at the Texas port. Three million gallons of the total 38 million gallons of light Angolan Palanca crude oil on board the tanker were able to be transferred to the Fraqmura before the blast. [ 4 ] Two days after the initial blast, there were five successive explosions in a ten-minute window. These explosions greatly increased the rate of the spill from the tanker into the water. By the end of that day (June 11) the tanker stern had dropped 58 feet and had stabilized five feet above the water line. [ 3 ] This was either due to shifting cargo or the tanker taking on water, which would be an indication of the vessel’s imminent sinking.
The light crude oil spilled in the Mega Borg incident was brown and evaporated much quicker than the heavy crude oil in spills such as the Exxon Valdez . This means that the oil is less likely to heavily coat nearby beaches, flora and fauna, however the tanker was carrying more oil than the Exxon Valdez incident spilled in total, so there was a lot of concern about the oil not being able to evaporate if the slick became too thick. [ 3 ]
The fire caused by the initial explosion took eight days to burn out, making it hard for firefighters to board the tanker and stop the leakage of oil. [ 3 ] However, the fire was helpful in the fact that it functioned as a natural in situ burning – out of the over 4.6 million spilled gallons, only 12,000 to 40,000 were left after the fire had burned out both on the water and on the tanker. [ 4 ]
Two days after the spill, on Monday June 11, eight ships with skimmers , booms, and fire equipment encircled the Mega Borg , with 12 more ships on the way. The Elf Acquitane Petroleum Company of Houston (owners of part of the Mega Borg ’s cargo) used planes to spread dispersants within five miles of the site of the tanker’s explosion. [ 3 ] By June 13, the previously 30 mile by 10 mile oil sheen [ 5 ] had diminished to 13 miles long by 5 miles wide. [ 2 ]
After an eight-day-long fire, from June 8 to June 16, the Coast Guard was able to contain and put out the flames. This then allowed for workers to stabilize the engine room and begin pumping out and unloading any remaining oil. [ 4 ] Once the fire was stopped, “high seas barrier booms were brought in to contain the rest of the leaked oil [ 6 ] During the eight days the fire lasted, firefighters were continuously cooling the ship with both water and, once the fire had sufficiently died down, with foam cannons. [ 7 ] One, however experimental, part of the cleanup process was the release of about 100 pounds of bacteria over an acre of the slick. Known as bioremediation , this process has been used in labs, but never before on the open ocean. The microbes work by breaking down oil by “eating” it and turning the “hydrocarbons into more benign byproducts .” The only drawback to this method was that, at the time, scientists were unsure about whether or not the bacteria cause more toxins to be released into the water. [ 8 ] A “slick-sucking vessel” was sent by the Coast Guard and was waiting on standby in case the Mega Borg sank and released its entire load of oil into the ocean. [ 9 ]
The nearest fire control equipment of the type necessary for a fire of this size and type was in Louisiana , so it had to be shipped in and was not available as quickly as some people believe it should have been. Additional equipment was shipped in from the Netherlands , adding to the belief that it could have been found closer to the spill site and thus the oil could have been contained earlier. [ 3 ] Local officials in Galveston argued that the decision to use foreign equipment delayed cleanup by two days, but Tony Redding, a spokesman for the Dutch company that lead the salvage (Smit Tak B.V.), said that all of the necessary materials were assembled “less than a day after the initial explosion” and that "Absolutely no delay was encountered as a result of the airlifting of equipment from Europe.” [ 4 ]
Some local officials also asked why foam was not used until five days after the explosion. Redding answered this by explaining that “A foam attack without extensive cooling has no chance of killing a fire of this type.” [ 4 ]
The explosion’s initial damage was inflicted on the 41 crew members aboard – two of them died, two disappeared and are presumed dead, and 17 were injured. [ 3 ]
The Gulf of Mexico is one of the United States’ richest fishing grounds, [ 10 ] and the Mega Borg spill added to an abundance of oil spills that have happened in the area. This affects not only marine microorganisms in deep waters, but larger deep-water fish and thus both recreational and commercial fishermen. Additionally, the National Wildlife Refuges near Galveston’s shores, nearby salt marches, and oyster reefs were all in potential danger depending on the extent of the slick’s spread. [ 3 ]
On June 29, 1990, it was reported that tar balls from the Mega Borg spill were appearing as far away as Louisiana beaches. [ 11 ]
The Mega Borg spill brought attention to the 984 protocols of legislation that have been held up in Senate since 1985. The Protocols passed the House, but have not been ratified due to arguments over international liabilities and whether or not the US should join international funding groups for oil spills. If ratified, the protocols would do a number of things including create multiple new federal response teams and a new fleet of special containment booms and skimmers. [ 12 ] | https://en.wikipedia.org/wiki/Mega_Borg_oil_spill |
Mega Builders is a documentary television series appearing on the Discovery Channel and Science Channel . Each episode takes a look into the people and the machines involved into the construction of many huge engineering projects.
Discovery Channel Taiwan broadcast a version of the series in 2022 that covered how the residential high-rise building Tao Zhu Yin Yuan was built over 11 years. [ 1 ]
Noting that the show covers the Bhumibol Bridge , Gotthard Base Tunnel , and North American and Madrid initiatives to reduce traffic congestion , The Daily Telegraph ' s Kirsty Heysen said, "This great series some of these hugely ambitious undertakings." [ 4 ] Brad Newsome of The Age praised the show, writing, "It's not your average construction-telly yawn tonight as we follow the annual building of Sweden's famed ice hotel." [ 5 ] The Sunday Mail stated, "Colourful characters and bigger-than Ben Hur projects fill this latest series about the world's largest and most mind-boggling engineering challenges." [ 6 ] The Brazilian newspaper Correio 24 Horas [ pt ] wrote that Mega Builders "is quite enlightening about the reasons why Rio de Janeiro , the Olympic city, is currently left without any good-quality stadium in working order". [ 7 ] | https://en.wikipedia.org/wiki/Mega_Builders |
A megabias , or a taphonomic megabias , is a large-scale pattern in the quality of the fossil record that affects paleobiologic analysis at provincial to global levels and at timescales usually exceeding ten million years. [ 1 ] It can result from major shifts in intrinsic and extrinsic properties of organisms, including morphology and behaviour in relation to other organisms, or shifts in the global environment, which can cause secular or long-term cyclic changes in preservation. [ 1 ]
The fossil record exhibits bias at many different levels. At the most basic level, there is a global bias towards biomineralizing organisms [ Note 1 ] , because biomineralized body parts are more resistant to decay and degradation. Due to the principle of uniformitarianism , [ 3 ] there is a basic assumption in geology that the formation of rocks has occurred by the same naturalistic processes throughout history, and thus that the reach of such biases remains stable over time. A megabias is a direct contradiction of this, whereby changes occur in large scale paleobiologic patterns. This includes:
It is generally assumed that the quality of the fossil record decreases globally and across all taxa with increasing age, because more time is available for the diagenesis and destruction of both fossils and enclosing rocks, [ 4 ] and thus the term "megabias" is usually used to refer to global trends in preservation. However, it has been noted that the fossil record of some taxa actually improves with greater age. [ 4 ] Examples such as this, and other related paleobiological trends, clearly indicate the action of a megabias, but only within one particular taxon. Hence, it is necessary to define four classes of megabias related to the reach of the bias, first defined by Kowalewski and Flessa.
A change in the quality of a single taxon's record. It may happen whenever evolutionary, environmental, or geologic trends affect the taxon's fossilization potential. [ 4 ]
This occurs when the fossilization potential varies from group to group. Among-taxon megabiases include both static and dynamic distortions. A static megabias is constant through time. For example, flatworms have always had a poor record relative to mollusks because mollusks as a taxon are almost always biomineralizing, whereas flatworms are almost never biomineralizing.
A dynamic megabias occurs when the fossilization potential of one group relative to that of another group changes through time. For example, lingulide brachiopods had a lower fossilization potential than articulate brachiopods, but only in the early Paleozoic. [ 5 ] This has changed through time, governed by changes in bathymetry and lateral shifts in lithofacies associated with basin evolution. By the Middle Ordovician, articulates had diversified to become important components of all marine environments except the deep basin; inarticulates were most important in offshore and basinal settings. By moving away from the main taphonomic window [ clarification needed ] , the inarticulates sacrificed their fossilization potential whilst not necessarily decreasing their biological diversity.
A global megabias is one that occurs over the whole world, though not necessarily in all depositional environments. There are numerous documented examples of this, many of which concern the Cambrian explosion and the Ediacaran fauna, both divisive subjects within the paleobiological community.
Many fossils, such as the Cambrian Small Shelly Fauna (SSF), are preserved through secondary phosphatization. Such preservation can boost the diversity estimates in three ways: [ 6 ]
The number of phosphatic facies deposits decreases significantly from the early- to mid-Cambrian. Most probably, this is the cause for the pattern of SSF diversity decline after the Botomian extinction . Whilst there may well have been a significant extinction worldwide of small shelly fossils, a significant decrease in the abundance of phosphatized facies may have caused the decline in SF diversity to appear much more severe than it really was.
It has been noted after the last 20 years that Exceptional Faunas, a particular class of Konservat- Lagerstätten exemplified by Burgess shale deposits, are statistically overabundant [ 7 ] considering their age and style of preservation. This problem is also known as the "Post-Cambrian closure of the deep-water slope-basin taphonomic window". It seems that the cause of this may have been ecological, at least in the root cause; a post-Cambrian changes in the amount of bioturbation in deeper-water low oxygen environments increased sedimentary porosity and thus enhanced microbial activity and accelerated rates of decay. [ 7 ] These higher rates of decay after the Cambrian meant that many soft bodied organisms were destroyed before the opportunity for preservation arose. | https://en.wikipedia.org/wiki/Megabias |
A megadiverse country is one of a group of nations that house the majority of Earth's species and high numbers of endemic species . Conservation International identified 17 megadiverse countries in 1998, [ 1 ] [ 2 ] all of which are located at least partially in tropical or subtropical regions.
Megadiversity means to exhibit great biodiversity . The main criterion for megadiverse countries is endemism at the level of species, genera and families. A megadiverse country must have at least 5,000 species of endemic plants and must border marine ecosystems.
In alphabetical order, the 17 megadiverse countries are: [ 1 ] | https://en.wikipedia.org/wiki/Megadiverse_countries |
Megaevolution describes the most dramatic events in evolution . It is no longer suggested that the evolutionary processes involved are necessarily special, although in some cases they might be. Whereas macroevolution can apply to relatively modest changes that produced diversification of species and genera and are readily compared to microevolution , "megaevolution" is used for great changes. Megaevolution has been extensively debated because it has been seen as a possible objection to Charles Darwin 's theory of gradual evolution by natural selection . [ 1 ]
A list was prepared by John Maynard Smith and Eörs Szathmáry which they called The Major Transitions in Evolution . [ 2 ] [ 3 ] On the 1999 edition of the list they included:
Some of these topics had been discussed before. [ 4 ] [ 5 ] [ 6 ] [ 7 ] [ 8 ] [ 9 ] [ 10 ] [ 11 ]
Numbers one to six on the list are events which are of huge importance, but about which we know relatively little. All occurred before (and mostly very much before) the fossil record started, or at least before the Phanerozoic eon .
Numbers seven and eight on the list are of a different kind from the first six, and have generally not been considered by the other authors. Number four is of a type which is not covered by traditional evolutionary theory, The origin of eukaryotic cells is probably due to symbiosis between prokaryotes. This is a kind of evolution which must be a rare event. [ 12 ] [ 13 ] [ 14 ]
The Cambrian explosion or Cambrian radiation was the relatively rapid appearance of most major animal phyla around 530 million years ago (mya) in the fossil record, some of which are now extinct. [ 15 ] [ 16 ] [ 17 ] It is the classic example of megaevolution. "The fossil record documents two mutually exclusive macroevolutionary modes separated by the transitional Ediacaran period". [ 18 ]
Before about 580 mya it seems that most organisms were simple. They were made of individual cells occasionally organized into colonies . Over the following 70 or 80 million years the rate of evolution accelerated by an order of magnitude . [ 18 ] Normally rates of evolution are measured by the extinction and origination rate of species, but here we can say that by the end of the Cambrian every phylum, or almost every phylum, existed.
The diversity of life began to resemble that of today. [ 19 ]
The Cambrian explosion has caused much scientific debate. The seemingly rapid appearance of fossils in the 'primordial strata ' was noted as early as the mid 19th century, [ 20 ] and Charles Darwin saw it as one of the main objections that could be made against his theory of evolution by natural selection. [ 1 ] | https://en.wikipedia.org/wiki/Megaevolution |
Megaflora (from Greek μέγας megas "large" and Neo-Latin flora "plant life") refers to an exceptionally large plant species; Jared Farmer defined the term as "the largest vascular plants of a particular region, habitat, or epoch". [ 1 ] Examples of megaflora include the Sequoioideae of California, Pando (a large clonal organism of quaking aspen located in Utah), and a number of extinct plant species from the Mesozoic . [ 2 ] [ 3 ] [ 4 ]
Megaflora (along with megafauna ) are often seen as charismatic and have wide public appeal, making them particularly useful as the symbol or flagship species of conservation efforts. [ 5 ]
Most Proto-Indo-European mythologies feature Megaflora in the form of a World Tree , a Tree-of-Life, axis mundi , or Sacred Tree. Some examples are the Ashvattha in Hindu mythology, Yggdrasil in Norse mythology, and égig érő fa in Hungarian mythology. Notable texts like the Epic of Gilgamesh and the Book of Genesis contain similar motifs, drawing inspiration from ancient iconography. [ 6 ]
Often symbolizing rootedness, spirituality and fruitfulness, these plants have become central to the high fantasy and science fiction genres. The Two Trees of Valinor from The Lord of The Rings and the Hometrees of Avatar are two mainstream examples.
This botany article is a stub . You can help Wikipedia by expanding it . | https://en.wikipedia.org/wiki/Megaflora |
Megagametogenesis is the process of maturation of the female gametophyte, or megagametophyte, in plants. [ 1 ] During the process of megagametogenesis, the megaspore, which arises from megasporogenesis, develops into the embryonic sac, in which the female gamete is housed. [ 2 ] These megaspores then develop into the haploid female gametophytes. [ 2 ] This occurs within the ovule, which is housed inside the ovary. [ 3 ]
Prior to megagametogenesis, a developing embryo undergoes meiosis during a process called megasporogenesis. Next, three out of four megaspores disintegrate, leaving only the megaspore that will undergo the megagametogenesis. [ 3 ] The following steps are shown in Figure 1, and detailed below.
Plants exhibit three main types of megagametogenesis. The number of haploid nuclei in the functional megaspore that is involved in megagametogenesis is the main difference between these three types. [ 7 ]
The most common type of megagametogenesis, monosporic megagametogenesis, is outlined above. This type of megagemetogenesis only allows one megaspore to undergo megagametogenesis, while the other three undergo programmed cell death. [ 8 ]
As the name implies, bisporic megagametogenesis involves two genetically different haploid nuclei. [ 9 ]
In eudicot plants, the entire process happens inside the ovule of a plant. The details of the process vary by species, but the process described here is common. This process starts with a single diploid megasporocyte in the nucleus. This megasporocyte undergoes meiotic cell division to form four cells that are haploid . Three cells die and one that is most distant from the micropyle develops into the megaspore. This megaspore becomes larger and the nucleus of it undergoes mitosis three times until there are eight nuclei. These eight nuclei are then arranged into two groups of four. These groups both send a nucleus to the center of the cell which then becomes the polar nuclei. The three cells left at the end of the cell near the micropylar become the egg apparatus with an egg cell in the center and two synergids. A cell wall forms around the other set of nuclei and forms the antipodals. The cells in the center develop into the central cell. This entire structure with its eight nuclei is called the embryonic sac.
Megagametogenesis creates the female gametophyte, which is an integral part of pollination, a very prominent process in plants. The male counterpart to megagametogenesis is called microgametogenesis. Microgametogenesis is the process of the formation of the male gametophyte. During pollination, the female gametophyte communicates with the pollen tube to ensure that it comes in contact with the ovule. [ 6 ] When contact is made, the pollen tube grows through the micropyle opening into a synergid cell, that dies when this occurs. The death of the synergid cell signals to the pollen tube to release the sperm. [ 6 ] This process creates the embryo, seed coat, and endosperm which, after pollination, will become crucial parts of the seed. [ 6 ]
Pollination is an essential process of global crop production. [ 10 ] Its success is economically crucial for farmers. [ 10 ] Additionally, pollination success is required for global food security. Cereals, or the seeds of grain crops, are most important staple food to humans around the world. They make up 48% of the calories consumed by humans. [ 11 ] | https://en.wikipedia.org/wiki/Megagametogenesis |
The megahertz myth , or in more recent cases the gigahertz myth , refers to the misconception of only using clock rate (for example measured in megahertz or gigahertz) to compare the performance of different microprocessors . While clock rates are a valid way of comparing the performance of different speeds of the same model and type of processor, other factors such as an amount of execution units , pipeline depth , cache hierarchy , branch prediction , and instruction sets can greatly affect the performance when considering different processors. For example, one processor may take two clock cycles to add two numbers and another clock cycle to multiply by a third number, whereas another processor may do the same calculation in two clock cycles. Comparisons between different types of processors are difficult because performance varies depending on the type of task. A benchmark is a more thorough way of measuring and comparing computer performance .
The myth started around 1984 when comparing the Apple II with the IBM PC . [ citation needed ] The argument was that the IBM computer was five times faster than the Apple II, as its Intel 8088 processor had a clock speed roughly 4.7 times the clock speed of the MOS Technology 6502 used in the latter. However, what really matters is not how finely divided a machine's instructions are, but how long it takes to complete a given task. Consider the LDA # (Load Accumulator Immediate) instruction. On a 6502 that instruction requires two clock cycles, or 2 μs at 1 MHz. Although the 4.77 MHz 8088's clock cycles are shorter, the LDA # needs at least [ 1 ] 4 of them, so it takes 4 / 4.77 MHz = 0.84 μs at least. So, at best, that instruction runs only a little more than 2 times as fast on the original IBM PC than on the Apple II.
The x86 CISC based CPU architecture which Intel introduced in 1978 was used as the standard for the DOS based IBM PC , and developments of it still continue to dominate the Microsoft Windows market. An IBM RISC based architecture was used for the PowerPC CPU which was released in 1992. In 1994, Apple Computer introduced Macintosh computers using these PowerPC CPUs. Initially, this architecture met hopes for performance, and different ranges of PowerPC CPUs were developed, often delivering different performances at the same clock rate. Similarly, at this time the Intel 80486 was selling alongside the Pentium which delivered almost twice the performance of the 80486 at the same clock rate. [ 2 ]
The myth arose because the clock rate was commonly taken as a simple measure of processor performance, and was promoted in advertising and by enthusiasts without taking into account other factors. The term came into use in the context of comparing PowerPC-based Apple Macintosh computers with Intel-based PCs. Marketing based on the myth led to the clock rate being given higher priority than actual performance and led to AMD introducing model numbers giving a notional clock rate based on comparative performance to overcome a perceived deficiency in their actual clock rate. [ 3 ]
Comparisons between PowerPC and Pentium had become a staple of Apple presentations. At the New York City Macworld Expo on July 18, 2001, Steve Jobs in his " Stevenote " described an 867 MHz PowerPC G4 as completing a task in 45 seconds while a 1.7 GHz Pentium 4 took 82 seconds for the same task, saying that "the name that we've given it is the megahertz myth". [ 4 ] He then introduced senior hardware VP Jon Rubinstein who gave a tutorial describing how shorter pipelines gave better performance at half the clock rate. The online cartoon The Joy of Tech subsequently presented a series of cartoons inspired by Rubinstein's tutorial. [ 5 ]
From approximately 1995 to 2005, Intel advertised its Pentium mainstream processors primarily on the basis of clock speed alone, in comparison to competitor products from AMD. Press articles had predicted that computer processors may eventually run as fast as 10 to 20 gigahertz in the next several decades.
This continued up until about 2005, when the Pentium Extreme Edition was reaching thermal dissipation limits running at speeds of nearly 4 gigahertz. The processor could not go faster without requiring complex changes to the cooling design, such as microfluidic cooling channels embedded within the chip itself to remove heat rapidly.
This was followed by the introduction of the Core 2 desktop processor in 2006, which was a major change from previous Intel desktop processors, allowing nearly a 50% decrease in processor clock while retaining the same performance.
Core 2 had its beginnings in the Pentium M mobile processor, where energy efficiency was more important than raw power, and initially offered power-saving options not available in the Pentium 4 and Pentium D .
In the succeeding years after the demise of the NetBurst microarchitecture and its 3+ GHz CPUs, microprocessor clock speeds kept slowly increasing after initially dropping by about 1 GHz. Several years' advances in manufacturing processes and power management (specifically, the ability to set clock speeds on a per-core basis) allowed for clock speeds as high or higher than the old NetBurst Pentium 4s and Pentium Ds but with much higher efficiency and performance. As of 2018, many Intel microprocessors are able to exceed a base clock speed of 4 GHz (Intel Core i7-7700K and i3-7350K have a base clock speed of 4.20 GHz, for example).
In 2011, AMD was first able to break the 4 GHz barrier for x86 microprocessors with the debut of the initial Bulldozer based AMD FX CPUs. In June 2013, AMD released the FX-9590 which can reach speeds of up to 5.0 GHz, but similar issues with power usage and heat output returned.
Neither Intel nor AMD produced the first microprocessor across the industry to break the 4 GHz and 5 GHz barriers. The IBM z10 achieved 4.4 GHz in 2008, and the IBM z196 achieved 5.2 GHz in 2010, followed by the z12 achieving 5.5 GHz in Autumn 2012. | https://en.wikipedia.org/wiki/Megahertz_myth |
Megakaryocyte–erythroid progenitor cells ( MEPs ), among other blood cells , are generated as a result of hematopoiesis , which occurs in the bone marrow . Hematopoietic stem cells (HSC) can differentiate into one of two progenitor cells: the common lymphoid progenitor and the common myeloid progenitor. MEPs derive from the common myeloid progenitor lineage. [ 1 ] Megakaryocyte–erythroid progenitor cells must commit to becoming either platelet-producing megakaryocytes via megakaryopoiesis or erythrocyte-producing erythroblasts via erythropoiesis . [ 2 ] [ 3 ] Most of the blood cells produced in the bone marrow during hematopoiesis come from megakaryocyte–erythroid progenitor cells. [ 4 ]
This cell biology article is a stub . You can help Wikipedia by expanding it . | https://en.wikipedia.org/wiki/Megakaryocyte–erythroid_progenitor_cell |
Megamitochondria is extremely large and abnormal shapes of mitochondria seen in hepatocytes in alcoholic liver disease and in nutritional deficiencies . It can be seen in conditions of hypertrophy in cell death .
This article related to pathology is a stub . You can help Wikipedia by expanding it . | https://en.wikipedia.org/wiki/Megamitochondria |
Megan and Morag , two domestic sheep , were the first mammals to have been successfully cloned from differentiated cells. [ 1 ] They are not to be confused with Dolly the sheep which was the first animal to be successfully cloned from an adult somatic cell [ 2 ] or Polly the sheep which was the first cloned and transgenic animal. [ 3 ] Megan and Morag, like Dolly and Polly, were cloned at the Roslin Institute in Edinburgh , Scotland in 1995.
The team at the Roslin Institute were seeking a way to modify the genetic constitution of sheep and cattle more effectively than the hit and miss method that was the only method and had sort of aids available at the time – microinjection . In microinjection, DNA is injected into the pronuclei of fertilized oocytes. However, only a small proportion of the animals will integrate the injected DNA into their genome and in the rare cases that they do integrate this new genetic information, the pattern of expression of the injected piece of DNA's gene, due to the random integration, is very variable.
The team choose to combine two approaches – microinjection and embryonic stem cells . In order to achieve this they decided to try to transfer the nucleus from one cell to another and stimulate this new cell to grow and become an animal, a process known as nuclear transfer . The team at the Roslin Institute tried to make immortalized and undifferentiated embryonic stem cell lines in sheep, but failed. As a result, they decided to work with cultured blastocyst cells. The nuclear material of these blastocyst cells would be transferred into an unfertilized sheep egg cell, an oocyte where the nucleus had been removed. To optimize the chances of successful nuclear transfer, they put the cultured cells into a state of quiescence, which was a similar state to that of the unfertilized egg cell.
Nuclear transfer was done, using electrical stimuli both to fuse the cultured cell with the enucleated egg and to kick start embryonic development. From 244 nuclear transfers, 34 developed to a stage where they could be placed in the uteri of surrogate mothers. In the summer of 1995, five lambs were born, of which two – Megan and Morag – survived to become healthy fertile adults. These were the first mammals cloned from differentiated cells. They were born with the names 5LL2 and 5LL5 in June 1995.
The production of Megan and Morag demonstrated that viable sheep can be produced by nuclear transfer from cells which have been cultured in vitro. They signified the technical breakthrough that made Dolly the sheep possible. The birth of Megan and Morag, a year before Dolly, with their huge beneficial potential, made relatively few headlines. [ 4 ] As of 2005 [update] , Megan was still alive and was the oldest cloned animal at the time. [ 5 ] | https://en.wikipedia.org/wiki/Megan_and_Morag |
Meganucleases are endodeoxyribonucleases characterized by a large recognition site (double-stranded DNA sequences of 12 to 40 base pairs); as a result this site generally occurs only once in any given genome . For example, the 18-base pair sequence recognized by the I-SceI meganuclease would on average require a genome twenty times the size of the human genome to be found once by chance (although sequences with a single mismatch occur about three times per human-sized genome). Meganucleases are therefore considered to be the most specific naturally occurring restriction enzymes .
Among meganucleases, the LAGLIDADG family of homing endonucleases has become a valuable tool for the study of genomes and genome engineering over the past fifteen years.
Meganucleases are "molecular DNA scissors" that can be used to replace, eliminate or modify sequences in a highly targeted way. By modifying their recognition sequence through protein engineering, the targeted sequence can be changed. Meganucleases are used to modify all genome types, whether bacterial, plant or animal. They open up wide avenues for innovation, particularly in the field of human health, for example the elimination of viral genetic material or the "repair" of damaged genes using gene therapy.
Meganucleases are found in a large number of organisms – Archaea or archaebacteria, bacteria, phages , fungi, yeast , algae and some plants. They can be expressed in different compartments of the cell – the nucleus , mitochondria or chloroplasts . Several hundred of these enzymes have been identified.
Meganucleases are mainly represented by two main enzyme families collectively known as homing endonucleases: intron endonucleases and intein endonucleases.
In nature, these proteins are encoded by mobile genetic elements, introns or inteins . Introns propagate by intervening at a precise location in the DNA, where the expression of the meganuclease produces a break in the complementary intron- or intein-free allele . For inteins and group I introns, this break leads to the duplication of the intron or intein at the cutting site by means of the homologous recombination repair for double-stranded DNA breaks.
We know relatively little about the actual purpose of meganucleases. It is widely thought that the genetic material that encodes meganucleases functions as a parasitic element that uses the double-stranded DNA cell repair mechanisms to its own advantage as a means of multiplying and spreading, without damaging the genetic material of its host.
There are five families, or classes, of homing endonucleases. [ 1 ] The most widespread and best known is the LAGLIDADG family . LAGLIDADG family endonucleases are mostly found in the mitochondria and chloroplasts of eukaryotic unicellular organisms.
The name of this family corresponds to an amino acid sequence (or motif) that is found, more or less conserved, in all the proteins of this family. These small proteins are also known for their compact and closely packed three-dimensional structures.
The best characterized endonucleases which are most widely used in research and genome engineering include I-SceI (discovered in the mitochondria of baker's yeast Saccharomyces cerevisiae ), I-CreI (from the chloroplasts of the green algae Chlamydomonas reinhardtii ) and I-DmoI (from the archaebacterium Desulfurococcus mobilis ).
The best known LAGLIDADG endonucleases are homodimers (for example I-CreI, composed of two copies of the same protein domain) or internally symmetrical monomers (I-SceI). The DNA binding site, which contains the catalytic domain , is composed of two parts on either side of the cutting point. The half-binding sites can be extremely similar and bind to a palindromic or semi-palindromic DNA sequence (I-CreI), or they can be non-palindromic (I-SceI).
The high specificity of meganucleases gives them a high degree of precision and much lower cell toxicity than other naturally occurring restriction enzymes. Meganucleases were identified in the 1990s, and subsequent work has shown that they are particularly promising tools for genome engineering and gene editing , as they are able to efficiently induce homologous recombination, [ 2 ] generate mutations, [ 3 ] and alter reading frames. [ 4 ]
However, the meganuclease-induced genetic recombinations that could be performed were limited by the repertoire of meganucleases available. Despite the existence of hundreds of meganucleases in nature, and the fact that each one is able to tolerate minor variations in its recognition site, the probability of finding a meganuclease able to cut a given gene at the desired location is extremely slim. Several groups turned their attention to engineering new meganucleases that would target the desired recognition sites.
The most advanced research and applications concern homing endonucleases from the LAGLIDADG family.
To create tailor-made meganucleases, two main approaches have been adopted:
These two approaches can be combined to increase the possibility of creating new enzymes, while maintaining a high degree of efficacy and specificity. The scientists from Cellectis have been working on gene editing since 1999 and have developed a collection of over 20,000 protein domains from the homodimeric meganuclease I-CreI as well as from other meganucleases scaffolds. [ 11 ] They can be combined to form functional chimeric tailor-made heterodimers for research laboratories and for industrial purposes.
Precision Biosciences, another biotechnology company, has developed a fully rational design process called Directed Nuclease Editor (DNE) which is capable of creating engineered meganucleases that target and modify a user-defined location in a genome. [ 12 ] In 2012 researchers at Bayer CropScience used DNE to incorporate a gene sequence into the DNA of cotton plants, targeting it precisely to a predetermined site. [ 13 ]
One recent advance in the use of meganucleases for genome engineering is the incorporation of the DNA binding domain from transcription activator-like (TAL) effectors into hybrid nucleases. These "megaTALs" combine the ease of engineering and high DNA binding specificity of a TAL effector with the high cleavage efficiency of meganucleases. [ 14 ] In addition, meganucleases have been fused to DNA end-processing enzymes in order to promote error-prone non-homologous end joining [ 15 ] and to increase the frequency of mutagenic events at a given locus. [ 16 ]
As stated in the opening paragraph, a meganuclease with an 18-base pair sequence would on average require a genome twenty times the size of the human genome to be found once by chance; the calculation is 4 18 /3x10 9 = 22.9. However, very similar sequences are much more common, with frequency increasing quickly the more mismatches are permitted.
For example, a sequence that is identical in all but one base pair would occur by chance once every 4 17 /18x3x10 9 = 0.32 human genome equivalents on average, or three times per human genome. A sequence that is identical in all but two base pairs would on average occur by chance once every 4 16 /(18C2)x3x10 9 = 0.0094 human genome equivalents, or 107 times per human genome.
This is important because enzymes do not have perfect discrimination; a nuclease will still have some likelihood of acting even if the sequence does not match perfectly. So the activity of the nuclease on a sequence with one mismatch is less than the no-mismatch case, and activity is even less for two mismatches, but still not zero. Exclusion of these sequences, which are very similar but not identical, is still an important problem to be overcome in genome engineering.
DNA methylation and chromatin structure affect the efficacy of meganuclease digestion. [ 17 ] [ 18 ] A thorough consideration of the genetic and epigenetic context of a target sequence is therefore necessary for the practical application of these enzymes.
In December 2014, the USPTO issued patent 8,921,332 covering meganuclease-based genome editing in vitro. [ 19 ] This patent was licensed exclusively to Cellectis. [ 20 ] | https://en.wikipedia.org/wiki/Meganuclease |
Megaphone is a cytotoxic neolignan obtained from Aniba megaphylla , a flowering plant in the laurel family which gave the compound its name. Megaphone has also been prepared synthetically. [ 1 ] [ 2 ] [ 3 ]
Studies carried out in the 1960s demonstrated that an alcoholic extract of the ground root of Aniba megaphylla inhibited, in vitro , growth of cells derived from human carcinoma of the nasopharynx . In 1978, the active components of the extract were isolated using silica gel chromatography , characterized and named as megaphone (C 22 H 30 O 6 , solid), megaphone acetate (C 24 H 32 O 7 , oily liquid) and megaphyllone acetate (C 23 H 28 O 7 , oily liquid). For comparison, megaphone acetate was also produced synthetically by reacting megaphone with acetic anhydride at 50 °C for 6 hours. Stirring an alcoholic solution of megaphone (megaphone acetate), with added palladium catalyst, in hydrogen atmosphere, followed by evaporation of the solvent yields tetrahydromegaphone (tetrahydromegaphone acetate) as an oil. Millimeter-sized crystals of megaphone can be grown from an ether - chloroform solution. [ 4 ] They have monoclinic symmetry with space group P 2 1 , lattice constants a = 0.8757 nm, b = 1.1942 nm and c = 1.0177 nm and two formula units per unit cell . Megaphone and megaphone acetate molecules are chiral and the reported extraction and synthesis procedures yielded their racemic mixtures . [ 4 ] Megaphone acetate was also isolated from the root of Endlicheria dysodantha , another plant of Laurel family , using chromatography of ethanolic solution. It showed inhibitory activity against cells of crown gall tumor and human lung, breast and colon carcinomas. [ 5 ] | https://en.wikipedia.org/wiki/Megaphone_(molecule) |
Megaphorbs are areas with a community of tall, exuberant, perennial herbs. [ 1 ] The plant communities provide ground cover and often exist on the margins of wooded areas, terrain that has recently been cleared, [ 2 ] or in disturbed areas adjacent to creeks or rivers. These plant communities are often found in mountainous areas.
Areas that a megaphorb layer frequents are margins of wooded areas or forests that have recently been deforested or where logging has occurred. Given the now newly open area it provides ample conditions for a megaphorb layer to produce. Other areas in which megaphorbs may appear are along the banks of streams and rivers where there is a lack of plant life and nothing obstructing the upwards growth of the plants. The root systems provide structure to riverbanks, reducing erosion in seasons of heavy rainfall. Once peak growing conditions are over, the megaphorb layer begins to die off, which provides decaying plant material to the surrounding area. This feeds detritivore species, and eventually boosts the nutrient ratio within the soil.
This ecology -related article is a stub . You can help Wikipedia by expanding it . | https://en.wikipedia.org/wiki/Megaphorb |
A megaproject is an extremely large-scale construction and investment project . [ 1 ] A more general definition is "Megaprojects are temporary endeavours (i.e. projects) characterised by: large investment commitment, vast complexity (especially in organisational terms), and long-lasting impact on the economy, the environment, and society". [ 2 ]
Megaprojects refer not only to construction projects but also decommissioning projects, which are projects that can reach multi-billion budgets, and have a high level of innovation and complexity, and are affected by a number of techno-socio-economic and organizational challenges. [ 3 ] [ 4 ]
The OFCCP Mega Construction Project (Megaproject) Program involves projects valued at over $35 million. [ 5 ]
Megaprojects are often affected by corruption, leading to higher cost and lower benefit. [ 6 ]
According to the European Cooperation in Science and Technology (COST), megaprojects are characterized both by "extreme complexity (both in technical and human terms) and by a long record of poor delivery". [ 1 ] Megaprojects attract significant public attention because of substantial impacts on communities , environment , and budgets , and the high costs involved. [ 7 ] Megaprojects can also be defined as "initiatives that are physical, very expensive, and public". [ 8 ]
Megaprojects include special economic zones , public buildings , power plants , dams , airports , hospitals , seaports , bridges , highways , tunnels , railways , wastewater projects, oil and natural gas extraction projects, aerospace projects, weapons systems , information technology systems, large-scale sporting events and, more recently, mixed use waterfront redevelopments; however, the most common megaprojects are in the categories of hydroelectric facilities, nuclear power plants, and large public transportation projects. Megaprojects can also include large-scale high-cost initiatives in scientific research and infrastructure, such as the sequencing of the human genome , a significant global advance in genetics and biotechnology .
The logic [ by whom? ] on which many of the typical megaprojects are built is collective benefits; for example electricity for everybody (who can pay), road access (for those that have cars), etc. They may also serve as a means to open frontiers. [ 9 ] Megaprojects have been criticised for their top-down planning processes and their ill effects on certain communities. Large scale projects often advantage one group of people while disadvantaging another, for instance, the Three Gorges Dam in China, the largest hydroelectric project in the world, [ 10 ] required the displacement of 1.2 million farmers. [ 11 ] [ 12 ] In the 1970s, the highway revolts in some Western nations saw urban activists opposing government plans to demolish buildings for freeway route construction, on the basis that such demolitions would unfairly disadvantage the urban working class and benefit commuters. [ 13 ] Anti-nuclear protests against proposed nuclear power plants in the United States and Germany prevented developments due to environmental and social concerns. [ citation needed ]
More recently, [ when? ] new types of megaprojects have been identified that no longer follow the old models of being singular and monolithic in their purposes, but have become quite flexible and diverse, such as waterfront redevelopment schemes that seem to offer something to everybody. [ clarification needed ] [ citation needed ] However, just like the old megaprojects, the new ones also foreclose "upon a wide variety of social practices, reproducing rather than resolving urban inequality and disenfranchisement". [ 14 ] Because of their plethora of land uses "these mega-projects inhibit the growth of oppositional and contestational practices". [ 14 ] The collective benefits that are often the underlying logic of a mega-project, are here reduced to an individualized form of public benefit.
Proponents of infrastructure-based development advocate for funding large-scale projects to create long-term economic benefits. Investing in megaprojects in order to stimulate the general economy has been a popular policy measure since the economic crisis of the 1930s. Recent examples are the 2008–2009 Chinese economic stimulus program , the 2008 European Union stimulus plan , and the American Recovery and Reinvestment Act of 2009 .
Megaprojects often raise capital based on expected returns—though projects often go overbudget and over time, and market conditions like commodity prices can change. [ 15 ] Concern at cost overruns is often expressed by critics of megaprojects during the planning phase. If the megaproject is delivered in a country with relevant corruption the likelihood and magnitude of having overbudgets increases. [ 16 ]
One of the most challenging aspects of megaprojects is obtaining sufficient funding. Alan Altshuler and David Luberoff have found that creative and politically adept political leadership is required to secure resources as well as generate public support, mollify critics, and manage conflict through many years of planning, authorization and implementation. [ 17 ] Other challenges faced by those planning megaprojects include laws and regulations that empower community groups, contested information and methodologies, high levels of uncertainty, avoiding impacts on neighborhoods and the environment, and attempting to solve a wicked problem . [ 18 ] | https://en.wikipedia.org/wiki/Megaproject |
Megascale engineering (or macro-engineering ) [ 1 ] is a form of exploratory engineering concerned with the construction of structures on an enormous scale. [ 2 ] Typically these structures are at least 1,000 km (620 mi) in length—in other words, at least one megameter , hence the name. Such large-scale structures are termed megastructures .
In addition to large-scale structures, megascale engineering is also defined as including the transformation of entire planets into a human -habitable environment, a process known as terraforming or planetary engineering . This might also include transformation of the surface conditions, changes in the planetary orbit, and structures in orbit intended to modify the energy balance.
Astroengineering is the extension of megascale engineering to megastructures on a stellar scale or larger, [ 3 ] such as Dyson spheres , [ 4 ] Ringworlds , and Alderson disks .
Several megascale structure concepts such as Dyson spheres , Dyson swarms , and Matrioshka brains would likely be built upon space-based solar power satellites . Other planetary engineering or interstellar transportation concepts would likely require space-based solar power satellites and the accompanying space logistics infrastructure for their power or construction.
Megascale engineering often plays a major part in the plot of science fiction movies and books. The micro-gravity environment of outer space provides several potential benefits for the engineering of these structures. These include minimizing the loads on the structure, the availability of large quantities of raw materials in the form of asteroids , and an ample supply of energy from the Sun . The capabilities to employ these advantages are not yet available, however, so they provide material for science fiction themes .
Quite a few megastructures have been designed on paper as exploratory engineering. However, the list of existing and planned megastructures is complicated by the ambiguity in classifying what exactly constitutes a megastructure. By strict definition, no megastructures currently exist (with the space elevator being the only such project under serious consideration). By more lenient definitions, the Great Wall of China (6.7 Mm or 4,200 mi) counts as a megastructure.
A more complete list of conceptual and existing megastructures, along with a discussion of megastructure criteria, is found under megastructure .
Of all the proposed megastructures, only the orbital elevator , [ 5 ] the Lofstrom launch loop , and Martian or lunar space elevator concepts could be built using conventional engineering techniques, and are within the grasp of current material science . Carbon nanotubes may have the requisite tensile strength for the more technologically challenging Earth-based space elevator , but creation of nanotubes of the required length is a laboratory exercise, and adequate cable-scale technology has not yet been shown at all.
The assembly of structures more massive than a space elevator would likely involve a combination of new engineering techniques, new materials, and new technologies . Such massive construction projects might require the use of self-replicating machines to provide a suitably large "construction crew". The use of nanotechnology might provide both the self-replicating assemblers, and the specialized materials needed for such a project. Nanotechnology is, however, another area of speculative exploratory engineering at this time. | https://en.wikipedia.org/wiki/Megascale_engineering |
Megaspores , also called macrospores , are a type of spore that is present in heterosporous plants . These plants have two spore types, megaspores and microspores . Generally speaking, the megaspore, or large spore, germinates into a female gametophyte , which produces egg cells . These are fertilized by sperm produced by the male gametophyte developing from the microspore. Heterosporous plants include seed plants ( gymnosperms and flowering plants ), water ferns ( Salviniales ), spikemosses ( Selaginellaceae ) and quillworts ( Isoetaceae ).
In gymnosperms and flowering plants, the megaspore is produced inside the nucellus of the ovule . During megasporogenesis, a diploid precursor cell, the megasporocyte or megaspore mother cell, undergoes meiosis to produce initially four haploid cells ( the megaspores ). [ 1 ] Angiosperms exhibit three patterns of megasporogenesis: monosporic, bisporic, and tetrasporic , also known as the Polygonum type, the Alisma type, and the Drusa type, respectively. The monosporic pattern occurs most frequently (>70% of angiosperms) and is found in many economically and biologically important groups such as Brassicaceae (e.g., Arabidopsis , Capsella , Brassica ), Gramineae (e.g., maize, rice, wheat), Malvaceae (e.g., cotton), Leguminoseae (e.g., beans, soybean), and Solanaceae (e.g., pepper, tobacco, tomato, potato, petunia). [ 2 ]
This pattern is characterized by cell plate formation after meiosis 1 & 2, which results in four one-nucleate megaspores, of which three degenerate. The bisporic pattern is characterized by cell plate formation only after meiosis 1, and results in two two-nucleate megaspores, of which one degenerates. The tetrasporic pattern is characterized by cell plates failing to form after either meiosis 1 or 2, and results in one four-nucleate megaspore. Therefore, each pattern gives rise to a single functional megaspore which contains one, two, or four meiotic nuclei, respectively. [ 2 ] The megaspore then undergoes megagametogenesis to give rise to the female gametophyte.
After megasporogenesis, the megaspore develops into the female gametophyte (the embryo sac) in a process called megagametogenesis. The process of megagametogenesis varies depending on which pattern of megasporogenesis occurred. Some species, such as Tridax trilobata , Ehretia laevis , and Alectra thomsoni , can undergo different patterns of megasporogenesis and therefore different patterns of megagametogenesis.
If the monosporic pattern occurred, the single nucleus undergoes mitosis three times, producing an eight-nucleate cell. These eight nuclei are arranged into two groups of four. These groups both send a nucleus to the center of the cell; these become the polar nuclei. Depending on the species, these nuclei fuse before or upon fertilization of the central cell. The three nuclei at the end of the cell near the micropylar become the egg apparatus, with an egg cell in the center and two synergids. At the other end of the cell, a cell wall forms around the nuclei and forms the antipodals. Therefore, the resulting embryo sac is a seven-celled structure consisting of one central cell, one egg cell, two synergid cells, and three antipodal cells. [ 2 ] [ 3 ]
The bisporic and tetrasporic patterns undergo varying processes and result in varying embryo sacs as well. In Lilium which has a tetrasporic pattern, the central cell of the embryo sac is 4n. Therefore, upon fertilization the endosperm will be 5n rather than the typical 3n. [ 4 ] | https://en.wikipedia.org/wiki/Megaspore |
A megastructure (or macrostructure [ 1 ] ) is a very large artificial object, although the limits of precisely how large vary considerably. Some apply the term to any especially large or tall building. [ 2 ] [ 3 ] Some sources define a megastructure as an enormous self-supporting artificial construct. The products of megascale engineering or astroengineering are megastructures.
Most megastructure designs could not be constructed with today's level of industrial technology. This makes their design examples of speculative (or exploratory) engineering . Those that could be constructed tend to qualify as megaprojects . Examples of megaprojects are the Zuiderzee Works in the Netherlands and Burj Khalifa in Dubai , the UAE .
Megastructures are also an architectural concept popularized in the 1960s where a city could be encased in a single building, or a relatively small number of buildings interconnected. Such arcology concepts are popular in science fiction . Megastructures often play a part in the plot or setting of science fiction movies and books, such as Rendezvous with Rama by Arthur C. Clarke .
In 1968, Ralph Wilcoxen defined a megastructure as any structural framework into which rooms, houses, or other small buildings can later be installed, uninstalled, and replaced; and which is capable of "unlimited" extension. This type of framework allows the structure to adapt to the individual wishes of its residents, even as those wishes change with time. [ 4 ]
Other sources define a megastructure as "any development in which residential densities are able to support services and facilities essential for the development to become a self-contained community". [ 5 ]
Many architects have designed such megastructures. Some of the more notable such architects and architectural groups include the Metabolist Movement , Archigram , Cedric Price , Frei Otto , Constant Nieuwenhuys , Yona Friedman , and Buckminster Fuller . [ 6 ]
A number of theoretical structures have been proposed which may be considered megastructures.
Most stellar scale megastructure proposals are designs to make use of the energy from a sun-like star while possibly still providing gravity or other attributes that would make it attractive for an advanced civilization.
Related structures which might not be classified as individual stellar megastructures, but occur on a similar scale:
A number of structures have appeared in fiction which may be considered megastructures. | https://en.wikipedia.org/wiki/Megastructure |
Megastructures is a documentary television series appearing on the National Geographic Channel in the United States and the United Kingdom, Channel 5 in the United Kingdom, France 5 in France, and 7mate in Australia.
Each episode is an educational look of varying depth into the construction, operation , and staffing of various structures or construction projects, but not ordinary construction products.
Generally containing interviews with designers and project managers , it presents the problems of construction and the methodology or techniques used to overcome obstacles. In some cases (such as the Akashi-Kaikyo Bridge and Petronas Towers ) this involved the development of new materials or products that are now in general use within the construction industry.
Megastructures focuses on constructions that are extreme; in the sense that they are the biggest, tallest, longest, or deepest in the world. Alternatively, a project may appear if it had an element of novelty or are a world first (such as Dubai 's Palm Islands ). This type of project is known as a megaproject .
The series follows similar subjects as the History Channel 's Modern Marvels and Discovery Channel 's Extreme Engineering , covering areas of architecture, transport, construction and manufacturing.
In January 2020, Indonesian TV channel, NET interested to broadcasting Megastructures in Indonesia in July 2020. [ citation needed ] | https://en.wikipedia.org/wiki/Megastructures_(TV_series) |
In evolutionary biology , megatrajectories are the major evolutionary milestones and directions in the evolution of life .
Posited by A. H. Knoll and Richard K. Bambach in their 2000 collaboration, "Directionality in the History of Life," Knoll and Bamback argue that, in consideration of the problem of progress in evolutionary history, a middle road that encompasses both contingent and convergent features of biological evolution may be attainable through the idea of the megatrajectory:
We believe that six broad megatrajectories capture the essence of vectoral change in the history of life. The megatrajectories for a logical sequence dictated by the necessity for complexity level N to exist before N+1 can evolve...In the view offered here, each megatrajectory adds new and qualitatively distinct dimensions to the way life utilizes ecospace. [ 1 ]
According to Knoll and Bambach, the six megatrajectories outlined by biological evolution thus far are:
Milan M. Ćirković and Robert Bradbury, [ 2 ] [ 3 ] have taken the megatrajectory concept one step further by theorizing that a seventh megatrajectory exists: postbiological evolution triggered by the emergence of artificial intelligence at least equivalent to the biologically-evolved one, as well as the invention of several key technologies of the similar level of complexity and environmental impact, such as molecular nanoassembling or stellar uplifting . | https://en.wikipedia.org/wiki/Megatrajectory |
A Megohmmeter or insulation resistance tester, is a special type of ohmmeter used to measure the electrical resistance of insulators . [ 1 ] Insulating components, for example cable jackets, must be tested for their insulation strength at the time of commissioning and as part of maintenance of high voltage electrical equipment and installations.
For this purpose, megohmmeters, which can provide high DC voltages (typically in ranges from 500 V to 5 kV, some are up to 15 kV) at specified current capacity, are used. Acceptable insulator resistance values are typically 1 to 10 megohms , depending on the standards referenced.
Resistance to be measured is connected across the terminals i.e. connected in series with the deflecting coil and across the generator . When the current is supplied to the coils then they have torque in opposite directions.
If resistance to be measured is high, no current will flow through the deflecting coil, the controlling coil, will, therefore, set itself perpendicular to the magnetic axis and hence set the pointer to the infinity .
If the resistance to be measured is small, high current flow through the deflecting coil and the resulting torque sets the pointer to zero.
For the intermediate value of resistance , depending upon the torque production, the pointer is set at a point between zero and infinity.
The hand-driven generator is of the permanent magnet type and it is designed to generate from 500 to 2500 volts . Testing voltage is produced by the rotation of the crank in a hand-operated megger, or by the battery in the case of an electronic-type megger. For testing a range up to 440V, equipment requires 550V DC is sufficient. The current coil or deflecting coil is series-connected and allows the electric current to flow through the circuit being tested.
Control and deflecting coil has a current limiting resistor connected in series so as to protect the external circuit in case of damages caused due to very low resistance. Testing voltage is produced by electromagnetic induction in case of hand-operated megger and by a battery in case of electronic type megger. The deflection of pointer increases with the increases in voltage in the external circuit and also decreases with the increase in current. That is, resultant torque is inversely related to current and directly related to voltage. While the electrical circuit that is being tested is open, the resultant torque caused due to voltage coil is maximum and the deflection pointer shows the value of ‘infinity’ which means the circuit does not have any shorting present and resistance is the maximum within the circuit being tested. In the case of a short circuit , the deflection pointer shows ‘zero’ which indicates ‘no’ resistance in the circuit being tested.
A Megger consists of an EMF source and voltmeter . The scale of the voltmeter is calibrated in ohms (kilo-ohms or megohms, as the case may be). In measurements, the EMF of the self-contained source must be equal to that of the source used in calibration. | https://en.wikipedia.org/wiki/Megohmmeter |
Mehdi Mollapour (born 1973) is a British-American biochemist and cancer biologist. He is a professor, vice chair for translational research and director of Renal Cancer Biology Program for the Department of Urology, and adjunct professor at the Department of Biochemistry and Molecular Biology at SUNY Upstate Medical University . [ 1 ] [ 2 ]
Mollapour holds a BSc (Hons) in microbiology and biochemistry from the University of East London , MSc in applied molecular biology of infectious diseases and diploma in tropical medicine and infectious diseases from the London School of Hygiene & Tropical Medicine . In 2001 he received his PhD in Biochemistry from the University College London . [ 1 ]
Mollapour completed his postdoctoral research at the University of Sheffield and in 2006 he received the Federation of European Societies (FEBS) fellowship. [ 1 ]
He joined the laboratory of Dr Len Neckers in Urological Oncology Branch, (Chief Dr. W. Marston Linehan), at the National Cancer Institute as a research fellow in 2007. [ 2 ]
In 2013 he joined the Department of Urology at the Upstate Medical University as an assistant professor. He became the Director of the Kidney Cancer Program within the same department in 2015. [ 1 ]
In 2018 he became the Professor of Urology and Adjunct Professor of Biochemistry and Molecular Biology at SUNY Upstate Medical University. He was also named the Vice Chair for Translational Research for the Department of Urology in the same year. [ 2 ] Mollapour was elected president of the Cell Stress Society International in 2023 and began his term in 2025. [ 3 ] Mollapour’s h-index is 49, based on almost 10,000 citations. [ 4 ]
Mollapour is widely recognized for his research on post-translation regulation of the molecular chaperone Heat shock protein-90 ( Hsp90 ) [ 5 ] [ 6 ] and co-chaperones in cancer. His work demonstrated how reversible biochemical reactions can become directional and ordered, and in general, how a house-keeping machine (Hsp90) can be modulated through signaling inputs and consequently regulating many cellular pathways such cell cycle, steroid hormone receptor and autophagy. [ 7 ] [ 8 ] [ 9 ]
Mollapour’s finding on canonical and non-canonical post-translational modifications of the Hsp90 chaperone machinery has also explained the reasons for tumors sensitivity and selectivity towards the Hsp90 inhibitors. [ 10 ] [ 6 ] [ 11 ]
Mollapour’s laboratory has discovered the tumor suppressor TSC1 and FNIPs function as the new co-chaperones of Hsp90. [ 12 ] [ 13 ] [ 14 ] [ 15 ] These two proteins are involved in Tuberous Sclerosis Complex and Birt–Hogg–Dubé syndrome (BHD) syndromes respectively. His research has identified a cross-talk between these two co-chaperones and demonstrated interconnectivity and compensatory mechanisms between the BHD and TSC pathways. [ 6 ]
Mutations and loss of function of the Von Hippel-Lindau (VHL) tumor suppressor gene play a causal role in the pathogenesis of clear cell renal carcinomas (ccRCC), a pathological subtype that accounts for the majority kidney cancer each year. Mollapour work has shown that VHL ubiquitinates protein phosphatase-5 (PP5) for proteasomal degradation in a hypoxia- and prolyl-hydroxylation-independent manner. VHL-deficient ccRCC cell lines and patient tumors exhibit elevated PP5 levels. Downregulation of PP5 causes activation of the extrinsic apoptotic pathway in ccRCC cells, suggesting a prosurvival role for PP5 in kidney cancer cancer cells, regulated by phosphorylation and ubiquitination. [ 16 ] [ 17 ] [ 18 ] Building on this foundation, Mollapour's team developed a selective PP5 inhibitor, demonstrating its ability to activate the extrinsic apoptotic pathway in kidney cancer cells by disrupting complex II. These findings not only elucidate the molecular mechanisms underlying kidney cancer progression but also present potential new therapeutic strategies for treatment. [ 19 ]
Mollapour’s research group has been supported by grants from the National Institutes for General Medical Science and the National Cancer Institute and US Department of Veterans Affairs to design and examine novel therapeutic strategies for patients with kidney , bladder and breast cancer .
Aerobic glycolysis in cancer cells, also known as the “Warburg effect”, is driven by hyperactivity of lactate dehydrogenase-A (LDHA). Mollapour’s team has identified the human tumor suppressor folliculin (FLCN) as a binding partner and uncompetitive inhibitor of LDHA. Their work has provided a new paradigm for the regulation of glycolysis. Cancer cells that experience the Warburg effect show FLCN dissociation from LDHA. Mollapour’s lab has shown that treatment of these cancer cells with a decapeptide derived from the FLCN loop region caused cell death, therefore providing a new avenue for targeted therapy in these cancers. [ 20 ] [ 21 ]
Mollapour is actively involved in kidney cancer patient advocacy. He serves on the scientific advisory panel for KidneyCAN, a patient-created and patient-driven movement dedicated to accelerating cures for kidney cancer. [ 22 ] Mollapour's commitment to rare kidney cancer research is further exemplified by his membership on the Birt-Hogg-Dubé (BHD) Science Advisory Board. This board is part of the Myrovlytis Trust, a UK charity founded in 2007 to promote research into rare conditions and advance public education in medical and molecular genetics. [1]
Sager RA, Woodford MR, Backe SJ, Makedon AM, Baker-Williams AJ, DiGregorio BT, Loiselle DR, Haystead TA, Zachara NE, Prodromou C, Bourboulia D, Schmidt LS, Linehan WM, Bratslavsky G, Mollapour M . Post-translational Regulation of FNIP1 Creates a Rheostat for the Molecular Chaperone Hsp90 . Cell reports. 2019;26(5):1344-56 e5. Epub 2019/01/31. doi: 10.1016/j.celrep.2019.01.018. PubMed PMID 30699359 ; PubMed Central PMCID: PMCPMC6370319.
Woodford MR, Hughes M, Sager RA, Backe SJ, Baker-Williams AJ, Bratslavsky MS, Jacob JM, Shapiro O, Wong M, Bratslavsky G, Bourboulia D, Mollapour M . Mutation of the co-chaperone Tsc1 in bladder cancer diminishes Hsp90 acetylation and reduces drug sensitivity and selectivity . Oncotarget. 2019;10(56):5824-34. doi: 10.18632/oncotarget.27217. PubMed PMID 31645902 ; PubMed Central PMCID: PMCPMC6791385.
Sager RA, Woodford MR, Mollapour M . The mTOR Independent Function of Tsc1 and FNIPs . Trends Biochem Sci. 2018;43(12):935-7. Epub 2018/10/27. doi: 10.1016/j.tibs.2018.09.018. PubMed PMID 30361061 .
Sager RA, Woodford MR, Neckers L, Mollapour M . Detecting Posttranslational Modifications of Hsp90 . Methods Mol Biol. 2018;1709:209-19. doi: 10.1007/978-1-4939-7477-1_16. PubMed PMID 29177662 .
Sager RA, Woodford MR, Shapiro O, Mollapour M , Bratslavsky G. Sporadic renal angiomyolipoma in a patient with Birt-Hogg-Dube: chaperones in pathogenesis . Oncotarget. 2018;9(31):22220-9. doi: 10.18632/oncotarget.25164. PubMed PMID 29774133 ; PubMed Central PMCID: PMCPMC5955167.
Woodford MR, Sager RA, Marris E, Dunn DM, Blanden AR, Murphy RL, Rensing N, Shapiro O, Panaretou B, Prodromou C, Loh SN, Gutmann DH, Bourboulia D, Bratslavsky G, Wong M, Mollapour M . Tumor suppressor Tsc1 is a new Hsp90 co-chaperone that facilitates folding of kinase and non-kinase clients . EMBO J. 2017. doi: 10.15252/embj.201796700. PubMed PMID 29127155 .
Dushukyan N, Dunn DM, Sager RA, Woodford MR, Loiselle DR, Daneshvar M, Baker-Williams AJ, Chisholm JD, Truman AW, Vaughan CK, Haystead TA, Bratslavsky G, Bourboulia D, Mollapour M . P hosphorylation and Ubiquitination Regulate Protein Phosphatase 5 Activity and Its Prosurvival Role in Kidney Cancer . Cell reports. 2017;21(7):1883-95. doi: 10.1016/j.celrep.2017.10.074. PubMed PMID 29141220 .
Bratslavsky G, Woodford MR, Daneshvar M, Mollapour M . Sixth BHD symposium and first international upstate kidney cancer symposium: latest scientific and clinical discoveries . Oncotarget. 2016. doi: 10.18632/oncotarget.7733. PubMed PMID 26933819 .
Woodford MR, Dunn D, Miller JB, Jamal S, Neckers L, Mollapour M . Impact of Posttranslational Modifications on the Anticancer Activity of Hsp90 Inhibitors . Adv Cancer Res. 2016;129:31-50. doi: 10.1016/bs.acr.2015.09.002. PubMed PMID 26916000 .
Woodford MR, Dunn DM, Blanden AR, Capriotti D, Loiselle D, Prodromou C, Panaretou B, Hughes PF, Smith A, Ackerman W, Haystead TA, Loh SN, Bourboulia D, Schmidt LS, Marston Linehan W, Bratslavsky G, Mollapour M . The FNIP co-chaperones decelerate the Hsp90 chaperone cycle and enhance drug binding . Nature communications. 2016;7:12037. doi: 10.1038/ncomms12037. PubMed PMID 27353360 ; PubMed Central PMCID: PMCPMC4931344.
Woodford MR, Dunn DM, Ciciarelli JG, Beebe K, Neckers L, Mollapour M . Targeting Hsp90 in Non-Cancerous Maladies . Curr Top Med Chem. 2016. PubMed PMID 27072697 .
Woodford MR, Truman AW, Dunn DM, Jensen SM, Cotran R, Bullard R, Abouelleil M, Beebe K, Wolfgeher D, Wierzbicki S, Post DE, Caza T, Tsutsumi S, Panaretou B, Kron SJ, Trepel JB, Landas S, Prodromou C, Shapiro O, Stetler-Stevenson WG, Bourboulia D, Neckers L, Bratslavsky G, Mollapour M . Mps1 Mediated Phosphorylation of Hsp90 Confers Renal Cell Carcinoma Sensitivity and Selectivity to Hsp90 Inhibitors . Cell reports. 2016d;14(4):872-84. doi: 10.1016/j.celrep.2015.12.084. PubMed PMID 26804907 .
Dunn DM, Woodford MR, Truman AW, Jensen SM, Schulman J, Caza T, Remillard TC, Loiselle D, Wolfgeher D, Blagg BS, Franco L, Haystead TA, Daturpalli S, Mayer MP, Trepel JB, Morgan RM, Prodromou C, Kron SJ, Panaretou B, Stetler-Stevenson WG, Landas SK, Neckers L, Bratslavsky G, Bourboulia D, Mollapour M . c-Abl Mediated Tyrosine Phosphorylation of Aha1 Activates Its Co-chaperone Function in Cancer Cells . Cell reports. 2015;12(6):1006-18. doi: 10.1016/j.celrep.2015.07.004. PubMed PMID 26235616 .
Mollapour M , Bourboulia D, Beebe K, Woodford MR, Polier S, Hoang A, Chelluri R, Li Y, Guo A, Lee MJ, Fotooh-Abadi E, Khan S, Prince T, Miyajima N, Yoshida S, Tsutsumi S, Xu W, Panaretou B, Stetler-Stevenson WG, Bratslavsky G, Trepel JB, Prodromou C, Neckers L. Asymmetric Hsp90 N Domain SUMOylation Recruits Aha1 and ATP-Competitive Inhibitors . Mol Cell. 2014;53(2):317-29. doi: 10.1016/j.molcel.2013.12.007. PubMed PMID 24462205 .
Mollapour is married to Dimitra Bourboulia, PhD, associate professor, Assistant Dean for Undergraduate and Graduate Medical Education Research, and Director for the Office of Research for Medical Students, at SUNY Upstate Medical University. [ 30 ] [ 31 ] | https://en.wikipedia.org/wiki/Mehdi_Mollapour |
The Mehler reaction is named after Alan H. Mehler, who, in 1951, presented data to the effect that isolated chloroplasts reduce oxygen to form hydrogen peroxide ( H 2 O 2 ). [ 1 ] Mehler observed that the H 2 O 2 formed in this way does not present an active intermediate in photosynthesis; rather, as a reactive oxygen species, it can be toxic to surrounding biological processes as an oxidizing agent . In scientific literature, the Mehler reaction often is used interchangeably with the Water-Water Cycle [ 2 ] to refer to the formation of H 2 O 2 by photosynthesis. Sensu stricto , the Water Water Cycle encompasses the Hill reaction , in which water is split to form oxygen, as well as the Mehler Reaction, in which oxygen is reduced to form H 2 O 2 and, finally, the scavenging of this H 2 O 2 by antioxidants to form water.
Beginning in the 1970s, Professor Kozi Asada elucidated that oxygen can be reduced by electrons emerging from ferredoxin of photosystem I , to form superoxide , which is then reduced by superoxide dismutase to form H 2 O 2 . This photochemical H 2 O 2 is then reduced by the action of ascorbate peroxidase to form water and oxidized ascorbate . Asada argued that oxygen presents an important sink for excess excitation energy acquired during plant exposure to bright light. He would often begin seminars by asking: 'Why aren't plants sunburnt despite being exposed to light?'. [ 3 ]
How much of a photoprotective role the Water Water Cycle plays has been occasion for some debate. In terrestrial plants, transfer of electrons to oxygen from ferredoxin at PSI accounts for easily less than 10% of total photosynthetic electron transport. [ 4 ] [ 5 ] [ 6 ] In algae and other uni-cellular photosynthetic organisms, however, this amount can account for 20 to 30% of total electron transport. It is possible that the reduction of oxygen by free electrons emerging from PSI prevents components of the electron transport chain from becoming over-reduced. [ 7 ]
The Water Water Cycle is not related to photorespiration , as it comprises different reactions and results in no net oxygen consumption. | https://en.wikipedia.org/wiki/Mehler_reaction |
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