Hill equation (biochemistry)
In biochemistry and pharmacology, the Hill equation refers to two related equations that reflect ligands binding to macromolecule. The distinction between the two equations is whether they measure response. Both equations are a function of the ligand concentration; as the Hill equation is formally equivalent to the Langmuir isotherm, it is sometimes referred to as the Hill-Langmuir equation. The International Union of Basic and Clinical Pharmacology has proposed to cement this subtle distinction and define separately the Hill-Langmuir equation, which reflects occupancy of receptors by ligands, the Hill equation, which reflects response to the ligand; this article will use the IUPHAR convention. A slight, yet subtle, distinction is made between the Hill-Langmuir equation, which reflects occupancy of receptors by ligands, the Hill equation, which reflects response to the ligand; the Hill-Langmuir equation was formulated by Archibald Hill in 1910 to describe the sigmoidal O2 binding curve of haemoglobin.
The binding of a ligand to a macromolecule is enhanced if there are other ligands present on the same macromolecule. The Hill-Langmuir equation is useful for determining the degree of cooperativity of the ligand binding to the enzyme or receptor; the Hill coefficient provides a way to quantify the degree of interaction between ligand binding sites. The Hill equation is important in the construction of dose-response curves; the Hill-Langmuir equation is a special case of a Rectangular hyperbola and is expressed in the following ways: θ = n K d + n = n n + n = 1 1 + n,where: θ is the fraction of the receptor protein concentration, bound by the ligand, is the free, unbound ligand concentration, K d is the apparent dissociation constant derived from the law of mass action, K A is the ligand concentration producing half occupation, n is the Hill coefficient. In pharmacology, θ is written as p A R, where A is the ligand, equivalent to L, R is the receptor. Θ can be expressed in terms of the total amount of receptor and ligand-bound receptor concentrations: θ =.
K d is equal to the ratio of the dissociation rate of the ligand-receptor complex to its association rate. Kd is the equilibrium constant for dissociation. K A is defined so that n = K d = k d k a, this is known as the microscopic dissociation constant and is the ligand concentration occupying half of the binding sites. In recent literature, this constant is sometimes referred to as K D; the Gaddum equation is a further generalisation of the Hill-equation, incorporating the presence of a reversible competitive antagonist. The Gaddum equation is derived to the Hill-equation but with 2 equilibria: both the ligand with the receptor and the antagonist with the receptor. Hence, the Gaddum equation has 2 constants: the equilibrium constants of the ligand and that of the antagonist The Hill plot is the rearrangement of the Hill-Langmuir Equation into a straight line. Taking the reciprocal of both sides of the Hill-Langmuir equation and inverting again yields
C0t analysis, a technique based on the principles of DNA reassociation kinetics, is a biochemical technique that measures how much repetitive DNA is in a DNA sample such as a genome. It is used to study genome structure and organization and has been used to simplify the sequencing of genomes that contain large amounts of repetitive sequence; the procedure involves heating a sample of genomic DNA until it denatures into the single stranded-form, slowly cooling it, so the strands can pair back together. While the sample is cooling, measurements are taken of how much of the DNA is base paired at each temperature; the amount of single and double-stranded DNA is measured by diluting the sample, which slows reassociation, binding the DNA to a hydroxylapatite column. The column is first washed with a low concentration of sodium phosphate buffer, which elutes the single-stranded DNA, with high concentrations of phosphate, which elutes the double stranded DNA; the amount of DNA in these two solutions is measured using a spectrophotometer.
Since a sequence of single-stranded DNA needs to find its complementary strand to reform a double helix, common sequences renature more than rare sequences. Indeed, the rate at which a sequence will reassociate is proportional to the number of copies of that sequence in the DNA sample. A sample with a highly-repetitive sequence will renature while complex sequences will renature slowly. However, instead of measuring the percentage of double-stranded DNA versus time, the amount of renaturation is measured relative to a C0t value; the C0t value is the product of C0, t, a constant that depends on the concentration of cations in the buffer. Repetitive DNA will renature at low C0t values, while complex and unique DNA sequences will renature at high C0t values; the fast renaturation of the repetitive DNA is because of the availability of numerous complementary sequences. C0t filtration is a technique that uses the principles of DNA renaturation kinetics to separate the repetitive DNA sequences that dominate many eukaryotic genomes from "gene-rich" single/low-copy sequences.
This allows DNA sequencing to concentrate on the parts of the genome that are most informative and interesting, which will speed up the discovery of new genes and make the process more efficient. It was first developed and utilized by Roy Britten and his colleagues at the Carnegie Institution of Washington in the 1960s. Of particular note, it was through C0t analysis that the redundant nature of eukaryotic genomes was first discovered. However, it wasn't until the breakthrough DNA reassociation kinetics experiments of Britten and his colleagues that it was shown that not all DNA coded for genes. In fact, their experiments demonstrated that the majority of eukaryotic genomic DNA is composed of repetitive, non-coding elements. Cot Analysis: An Overview Mississippi Genome Exploration Laboratory
Kinematics is a branch of classical mechanics that describes the motion of points and systems of bodies without considering the forces that caused the motion. Kinematics, as a field of study, is referred to as the "geometry of motion" and is seen as a branch of mathematics. A kinematics problem begins by describing the geometry of the system and declaring the initial conditions of any known values of position, velocity and/or acceleration of points within the system. Using arguments from geometry, the position and acceleration of any unknown parts of the system can be determined; the study of how forces act on bodies falls within kinetics, not kinematics. For further details, see analytical dynamics. Kinematics is used in astrophysics to describe the motion of celestial bodies and collections of such bodies. In mechanical engineering and biomechanics kinematics is used to describe the motion of systems composed of joined parts such as an engine, a robotic arm or the human skeleton. Geometric transformations called rigid transformations, are used to describe the movement of components in a mechanical system, simplifying the derivation of the equations of motion.
They are central to dynamic analysis. Kinematic analysis is the process of measuring the kinematic quantities used to describe motion. In engineering, for instance, kinematic analysis may be used to find the range of movement for a given mechanism and working in reverse, using kinematic synthesis to design a mechanism for a desired range of motion. In addition, kinematics applies algebraic geometry to the study of the mechanical advantage of a mechanical system or mechanism; the term kinematic is the English version of A. M. Ampère's cinématique, which he constructed from the Greek κίνημα kinema, itself derived from κινεῖν kinein. Kinematic and cinématique are related to the French word cinéma, but neither are directly derived from it. However, they do share a root word in common, as cinéma came from the shortened form of cinématographe, "motion picture projector and camera," once again from the Greek word for movement but the Greek word for writing. Particle kinematics is the study of the trajectory of a particle.
The position of a particle is defined as the coordinate vector from the origin of a coordinate frame to the particle. For example, consider a tower 50 m south from your home, where the coordinate frame is located at your home, such that East is the x-direction and North is the y-direction the coordinate vector to the base of the tower is r =. If the tower is 50 m high the coordinate vector to the top of the tower is r =. In the most general case, a three-dimensional coordinate system is used to define the position of a particle. However, if the particle is constrained to move in a surface, a two-dimensional coordinate system is sufficient. All observations in physics are incomplete without those observations being described with respect to a reference frame; the position vector of a particle is a vector drawn from the origin of the reference frame to the particle. It expresses both the distance of the point from its direction from the origin. In three dimensions, the position of point P can be expressed as P = = x P ı ^ + y P ȷ ^ + z P k ^, where x P, y P, z P are the Cartesian coordinates and ı ^, ȷ ^ and k ^ are the unit vectors along the x, y, z coordinate axes, respectively.
The magnitude of the position vector | P | gives the distance between the origin. | P | = x P 2 + y P 2 + z P 2. The direction cosines of the position vector provide a quantitative measure of direction, it is important to note. The position vector of a given particle is different relative to different frames of reference; the trajectory of a particle is a vector function of time, P, which defines the curve traced by the moving particle, given by P = x P ı ^ + y P ȷ ^ + z P k ^, where
Rigid body dynamics
Rigid-body dynamics studies the movement of systems of interconnected bodies under the action of external forces. The assumption that the bodies are rigid, which means that they do not deform under the action of applied forces, simplifies the analysis by reducing the parameters that describe the configuration of the system to the translation and rotation of reference frames attached to each body; this excludes bodies that display fluid elastic, plastic behavior. The dynamics of a rigid body system is described by the laws of kinematics and by the application of Newton's second law or their derivative form Lagrangian mechanics; the solution of these equations of motion provides a description of the position, the motion and the acceleration of the individual components of the system and overall the system itself, as a function of time. The formulation and solution of rigid body dynamics is an important tool in the computer simulation of mechanical systems. If a system of particles moves parallel to a fixed plane, the system is said to be constrained to planar movement.
In this case, Newton's laws for a rigid system of N particles, Pi, i=1... N, simplify. Determine the resultant force and torque at a reference point R, to obtain F = ∑ i = 1 N m i A i, T = ∑ i = 1 N ×, where ri denotes the planar trajectory of each particle; the kinematics of a rigid body yields the formula for the acceleration of the particle Pi in terms of the position R and acceleration A of the reference particle as well as the angular velocity vector ω and angular acceleration vector α of the rigid system of particles as, A i = α × + ω × + A. For systems that are constrained to planar movement, the angular velocity and angular acceleration vectors are directed along k perpendicular to the plane of movement, which simplifies this acceleration equation. In this case, the acceleration vectors can be simplified by introducing the unit vectors ei from the reference point R to a point ri and the unit vectors t i = k × e i, so A i = α − ω 2 + A; this yields the resultant force on the system as F = α ∑ i = 1 N m i − ω 2 ∑ i = 1 N m i + A, torque as T = ∑ i = 1 N × = α k → + × A, where e i × e i = 0 and e i × t i = k is the unit
Singapore Technologies Kinetics Ltd, in Singapore, is a strategic business area of ST Engineering and handles land systems and specialty vehicles. In 2000, ST Engineering acquired the Chartered Industries of Singapore through ST Automotive, a subsidiary of ST Engineering, the new company was named ST Kinetics. Given the initial charter of CIS to support the local defence requirements, the main defence customer of ST Kinetics remains as the Singapore Armed Forces. Besides manufacturing small arms and munitions, some of ST Kinetics' key military products include the SAR 21 assault rifle, the Bionix AFV, the Bronco All Terrain Tracked Carrier and the Terrex APC; these weapons and ammunition are made to U. S. or NATO specifications for export. The company holds a number of subsidiaries overseas in the U. S. Canada and India. Recent acquisitions between 2004 and 2009 have seen new construction equipment, specialised bodies and trailers for urban services being brought into ST Kinetics' stable of products, dominated by military weapons and platforms.
Together with the other ST Engineering companies, ST Kinetics is part of the Singapore Defence Ecosystem of users and producers in support of the Third Generation SAF. CIS was incorporated on 27 January 1967, when it started out by producing ordnance for the SAF. CIS' first product was the 5.56×45mm NATO round. Several other companies were formed under CIS over the span of the next 2 decades, with the expansion of the defence business, such as Unicorn International in 1971, Ordnance & Development Engineering in 1973, Singapore Test Services in 1980 and Chartered Chemicals in 1982. Shortly after the formation of CIS, the Defence Minister, Dr Goh Keng Swee, went on to set up several other government-linked defence industries to provide indigenous support for the SAF. One of them was Singapore Automotive Engineering. SAE was to support automotive-related services for the SAF, its first immediate task was to service and maintain a fleet of V200 armored vehicles. By 1982, amidst a young, thriving Singapore economy and having built up its capability in automotive servicing and standards, SAE saw the potential in the commercial sector and decided to incorporate SAE Inspection Centre for vehicle inspection and servicing.
The following year, Singapore Commuters, a taxi service, was formed. On 20 August 1991, SAE was publicly listed on the Singapore Stock Exchange. In the same year, SAE was renamed Singapore Technologies Automotive. STA Detroit Diesel-Allison was formed to take on the maintenance of the Detroit diesel engines and Allison transmission used in the Bionix as well as to distribute the Detroit Diesel parts in the Asian region. Singapore Commuters was merged with Singapore Airport Services Ltd and Singapore Bus Service Taxi Pte Ltd to form CitiCab in April 1995. By 1996, CIS through its various subsidiaries were producing various ordnance for the SAF and for export overseas. Chartered Ammunition Industries was producing small and large caliber ammunition, explosives and anti-tank weapons. ODE was producing medium to large caliber weapon systems. Chartered Firearms Industries was producing infantry and crew-served weapons, including the SR88A assault rifle, Ultimax 100, 7.62 mm GPMG, the 40 mm grenade launchers, the 40/50 Cupola Weapon system.
Allied Ordnance of Singapore was offering a range of advanced low-level air defence equipment, including the 40 mm L70 air defense gun system, missile and Optronic fire control systems. For the automotive business, ST Auto took on the AMX-13 Light Tank upgrading project, refurbished the M113 APC, Commando V100 and V200 armored vehicles, LARC V amphibious. ST Auto signed a contract with the SAF to overhaul and repair its military ground equipment. Singapore Test Services by was offering specialized tests and inspection services to both military and civilian customers. In 1997, ST Auto, together with Singapore Technologies Aerospace Ltd, Singapore Technologies Electronics Ltd, Singapore Technologies Marine Ltd, were merged to form the present ST Engineering. In October 1999, ST Engineering acquired CIS at S$78 M. ST Auto and CIS were merged in Feb 2000 to form ST Kinetics; the following year, ST Kinetics reorganised itself into 3 divisions, namely Automotive. A series of flagship products were developed by the early 21st century, including the SAR21 assault rifle, the Primus 155mm self-propelled artillery gun, the Pegasus 155 mm lightweight howitzer, the Bronco All-Terrain Tracked Carrier and the Terrex 8×8 Armoured Personnel Carrier.
ST Kinetics went on to invest in several companies overseas to enhance its engineering capabilities. An example was the acquisition of Silvatech Industries Inc in July 2006, a Canadian company specialising in forestry equipment, renaming it as Kinetics Drive Solutions in August 2006 to focus on the Infinitely Variable Transmissions that Silvatech had developed for its forestry equipment. 2003 was the year ST Kinetics decided to venture into the new commercial vehicles business to leverage on the engineering and fabrication capabilities it has acquired through the military vehicle projects. That year, ST Kinetics went into an equal-share joint venture with Beijing Heavy Duty Truck Plant to form the Beijing Zhonghuan Kinetics Heavy Vehicles Co. Ltd. In 2005, ST Kinetics acquired Special
Pharmacokinetics, sometimes abbreviated as PK, is a branch of pharmacology dedicated to determine the fate of substances administered to a living organism. The substances of interest include any chemical xenobiotic such as: pharmaceutical drugs, food additives, etc, it attempts to analyze chemical metabolism and to discover the fate of a chemical from the moment that it is administered up to the point at which it is eliminated from the body. Pharmacokinetics is the study of how an organism affects a drug, whereas pharmacodynamics is the study of how the drug affects the organism. Both together influence dosing and adverse effects, as seen in PK/PD models. Pharmacokinetics describes how the body affects a specific xenobiotic/chemical after administration through the mechanisms of absorption and distribution, as well as the metabolic changes of the substance in the body, the effects and routes of excretion of the metabolites of the drug. Pharmacokinetic properties of chemicals are affected by the route of administration and the dose of administered drug.
These may affect the absorption rate. Models have been developed to simplify conceptualization of the many processes that take place in the interaction between an organism and a chemical substance. One of these, the multi-compartmental model, is the most used approximations to reality; the various compartments that the model is divided into are referred to as the ADME scheme: Liberation – the process of release of a drug from the pharmaceutical formulation. See IVIVC. Absorption – the process of a substance entering the blood circulation. Distribution – the dispersion or dissemination of substances throughout the fluids and tissues of the body. Metabolism – the recognition by the organism that a foreign substance is present and the irreversible transformation of parent compounds into daughter metabolites. Excretion – the removal of the substances from the body. In rare cases, some drugs irreversibly accumulate in body tissue; the two phases of metabolism and excretion can be grouped together under the title elimination.
The study of these distinct phases involves the use and manipulation of basic concepts in order to understand the process dynamics. For this reason in order to comprehend the kinetics of a drug it is necessary to have detailed knowledge of a number of factors such as: the properties of the substances that act as excipients, the characteristics of the appropriate biological membranes and the way that substances can cross them, or the characteristics of the enzyme reactions that inactivate the drug. All these concepts can be represented through mathematical formulas that have a corresponding graphical representation; the use of these models allows an understanding of the characteristics of a molecule, as well as how a particular drug will behave given information regarding some of its basic characteristics such as its acid dissociation constant and solubility, absorption capacity and distribution in the organism. The model outputs for a drug can be used in industry or in the clinical application of pharmacokinetic concepts.
Clinical pharmacokinetics provides many performance guidelines for effective and efficient use of drugs for human-health professionals and in veterinary medicine. The following are the most measured pharmacokinetic metrics: In pharmacokinetics, steady state refers to the situation where the overall intake of a drug is in dynamic equilibrium with its elimination. In practice, it is considered that steady state is reached when a time of 4 to 5 times the half-life for a drug after regular dosing is started; the following graph depicts a typical time course of drug plasma concentration and illustrates main pharmacokinetic metrics: Pharmacokinetic modelling is performed by noncompartmental or compartmental methods. Noncompartmental methods estimate the exposure to a drug by estimating the area under the curve of a concentration-time graph. Compartmental methods estimate the concentration-time graph using kinetic models. Noncompartmental methods are more versatile in that they do not assume any specific compartmental model and produce accurate results acceptable for bioequivalence studies.
The final outcome of the transformations that a drug undergoes in an organism and the rules that determine this fate depend on a number of interrelated factors. A number of functional models have been developed in order to simplify the study of pharmacokinetics; these models are based on a consideration of an organism as a number of related compartments. The simplest idea is to think of an organism as only one homogenous compartment; this monocompartmental model presupposes that blood plasma concentrations of the drug are a true reflection of the drug's concentration in other fluids or tissues and that the elimination of the drug is directly proportional to the drug's concentration in the organism. However, these models do not always reflect the real situation within an organism. For example, not all body tissues have the same blood supply, so the distribution of the drug will be slower in these tissues than in others with a better blood supply. In addition, there are some tissues (s
Kinesiology is the scientific study of human or non-human body movement. Kinesiology addresses physiological and psychological dynamic principles and mechanisms of movement. Applications of kinesiology to human health include orthopedics. Studies of human and animal motion include measures from motion tracking systems, electrophysiology of muscle and brain activity, various methods for monitoring physiological function, other behavioral and cognitive research techniques; the word comes from the Greek κίνησις kínēsis, "movement", -λογία -logia, "study". Kinesiology is the study of human and nonhuman animal-body movements and function by applying the sciences of biomechanics, physiology and neuroscience. Applications of kinesiology in human-health include physical education teacher, rehabilitation and safety, health promotion, workplaces and exercise industries. A bachelor's degree in kinesiology can provide strong preparation for graduate study in biomedical research, as well as in professional programs, such as medicine.
Whereas the term "kinesiologist" is neither a licensed nor professional designation in the United States nor most countries, individuals with training in this area can teach physical education, provide consulting services, conduct research and develop policies related to rehabilitation, human motor performance and occupational health and safety. In North America, kinesiologists may study to earn a Bachelor of Science, Master of Science, or Doctorate of Philosophy degree in Kinesiology or a Bachelor of Kinesiology degree, while in Australia or New Zealand, they are conferred an Applied Science degree. Many doctoral level faculty in North American kinesiology programs received their doctoral training in related disciplines, such as neuroscience, mechanical engineering and physiology; the world's first kinesiology department was launched in 1967 at the University of Canada. Adaptation through exercise is a key principle of kinesiology that relates to improved fitness in athletes as well as health and wellness in clinical populations.
Exercise is a simple and established intervention for many movement disorders and musculoskeletal conditions due to the neuroplasticity of the brain and the adaptability of the musculoskeletal system. Therapeutic exercise has been shown to improve neuromotor control and motor capabilities in both normal and pathological populations. There are many different types of exercise interventions that can be applied in kinesiology to athletic and clinical populations. Aerobic exercise interventions help to improve cardiovascular endurance. Anaerobic strength training programs can increase muscular strength and lean body mass. Decreased risk of falls and increased neuromuscular control can be attributed to balance intervention programs. Flexibility programs can reduce the risk of injury; as a whole, exercise programs can reduce symptoms of depression and risk of cardiovascular and metabolic diseases. Additionally, they can help to improve quality of life, sleeping habits, immune system function, body composition.
The study of the physiological responses to physical exercise and their therapeutic applications is known as exercise physiology, an important area of research within kinesiology. Neuroplasticity is a key scientific principle used in kinesiology to describe how movement and changes in the brain are related; the human brain adapts and acquires new motor skills based on this principle, which includes both adaptive and maladaptive brain changes. Adaptive plasticity Recent empirical evidence indicates the significant impact of physical activity on brain function; the effects of physical activity can be distributed throughout the whole brain, such as higher gray matter density and white matter integrity after exercise training, and/or on specific brain areas, such as greater activation in prefrontal cortex and hippocampus. Neuroplasticity is the underlying mechanism of skill acquisition. For example, after long-term training, pianists showed greater gray matter density in sensorimotor cortex and white matter integrity in the internal capsule compared to non-musicians.
Maladaptive plasticity Maladaptive plasticity is defined as neuroplasticity with negative effects or detrimental consequences in behavior. Movement abnormalities may occur among individuals with and without brain injuries due to abnormal remodeling in central nervous system. Learned non-use is an example seen among patients with brain damage, such as stroke. Patients with stroke learned to suppress paretic limb movement after unsuccessful experience in paretic hand use. There are many types of therapies that are designed to overcome maladaptive plasticity in clinic and research, such as constraint-induced movement therapy, body weight support treadmill training and virtual reality therapy; these interventions are shown to enhance motor function in paretic limbs and stimulate cortical reorganization in patients with brain damage. Motor redundancy is a used concept in kinesiology and motor control which states that, for any task the human body can perform, there are an unlimited number of ways the nervous system could achieve that task.
This redundancy appears at multiple leve