title: Cardiopulmonary bypass

text: The components of the CPB circuit are interconnected by a series of tubes made of silicone rubber or PVC.


title: Cardiopulmonary bypass

text: Many CPB circuits now employ a centrifugal pump for the maintenance and control of blood flow during CPB. By altering the speed of revolution (RPM) of the pump head, blood flow is produced by centrifugal force. This type of pumping action is considered to be superior to the action of the roller pump by many because it is thought to prevent overpressurization, clamping or kinking of lines, and produce less damage to blood products (hemolysis, etc.).


title: Cardiopulmonary bypass

text: The pump console usually comprises several rotating motor-driven pumps that peristaltically "massage" tubing. This action gently propels the blood through the tubing. This is commonly referred to as a roller pump, or peristaltic pump. The pumps are more affordable than their centrifugal counterparts, but are susceptible to overpressurization if the lines become clamped or kinked. They are also more likely to cause a massive air embolism and require constant, close supervision by the perfusionist.


title: Cardiopulmonary bypass

text: The oxygenator is designed to add oxygen to infused blood and remove some of the carbon dioxide from the venous blood. Cardiac surgery was made possible by CPB using bubble oxygenators, but membrane oxygenators have supplanted bubble oxygenators since the 1980s. The main reasons for this are that membrane oxygenators tend to generate many fewer micro-bubbles, referred to as gaseous microemboli, which is generally considered harmful to the patient and reduce damage to blood cells, compared to bubble oxygenators. More recently, the use of hollow-fiber oxygenators has become more widespread. These derivatives of membrane oxygenators further reduce the occurrence of microemboli by reducing the direct air-blood interface while simultaneously providing adequate gas exchange.


title: Cardiopulmonary bypass

text: Another type of oxygenator gaining favour recently is the heparin-coated blood oxygenator which is believed to produce less systemic inflammation and decrease the propensity for blood to clot in the CPB circuit.


title: Cardiopulmonary bypass

text: Because hypothermia is frequently used in CPB to reduce metabolic demands (including that of the heart), heat exchangers are implemented to warm and cool blood within the circuit. The heating and cooling is accomplished by passing the line through a warm or ice water bath. A separate heat exchanger is required for the cardiopledgia line.


title: Cardiopulmonary bypass

text: Multiple cannulae are sewn into the patient's body in a variety of locations, depending on the type of surgery. A venous cannula removes oxygen depleted venous blood from a patient's body. An arterial cannula infuses oxygen-rich blood into the arterial system. The main determinants of cannula size selection is determined by the patient's size and weight, anticipated flow rate, and the size of the vessel being cannulated. A cardioplegia cannula delivers a cardioplegia solution to cause the heart to stop beating.


title: Cardiopulmonary bypass

text: Cardiopledgia is a fluid solution used to protect the heart during CPB. It is delivered via a cannula to the opening of the coronary arteries (usually by way of the aortic root) and/or to the cardiac veins (by way of the coronary sinus). These delivery methods are referred to antegrade and retrograde, respectively. Cardiopledgia solution protects the heart by arresting (i.e. stopping) the heart, thereby decreasing its metabolic demand. There are multiple types of cardiopledgia solutions, but most work by inhibiting fast sodium currents in the heart, thereby preventing conduction of the action potential. Other types of solutions act by inhibiting calcium's actions on myocytes.


title: Cardiopulmonary bypass

text: CPB requires significant forethought before surgery. In particular, the cannulation, cooling, and cardio-protective strategies must be coordinated between the surgeon, anesthesiologist, perfusionist, and nursing staff.


title: Cardiopulmonary bypass

text: The cannulation strategy varies on several operation-specific and patient-specific details. The typical arterial cannulation involves the placement of a single cannulation within distal ascending aorta. The most simple form on involves placement of a single cannula (known as a dual-stage cannula) passed through the right atrium and into the inferior vena cava. In some operations, such as those involving the tricuspid or mitral valve, two cannula are used—one is passed through the inferior vena cava and one through the superior vena cava. This is known as bi-caval cannulation.


title: Cardiopulmonary bypass

text: A CPB circuit must be primed with fluid and all air expunged from the arterial line/cannula before connection to the patient. The circuit is primed with a crystalloid solution and sometimes blood products are also added. Prior to cannulation (typically after opening the pericardium when using central cannulation), heparin or another anticoagulant is administered until the activated clotting time is above 480 seconds.


title: Cardiopulmonary bypass

text: The arterial cannulation site is inspected for calcification or other disease. Preoperative imaging or an ultrasound probe may be used to help identify aortic calcifications that could potentially become dislodged and cause an occlusion or stroke. Once the cannulation site has been deemed safe, two concentric, diamond-shaped pursestring sutures are placed in the distal ascending aorta. A stab incision with a scalpel is made within the pursestrings and the arterial cannula is passed through the incision. It is important the cannula is passed perpendicular to the aorta to avoid creating an aortic dissection. The pursestrings sutures are cinched around the cannula using a tourniquet and secured to the cannula. At this point, the perfusionist advances the arterial line of the CPB circuit and the surgeon connects the arterial line coming from the patient to the arterial line coming from the CPB machine. Care must be taken to ensure no air is in the circuit when the two are connected, or else the patient could develop an air embolism. Other sites for arterial cannulation include the axillary artery, brachiocephalic artery, or femoral artery.


title: Cardiopulmonary bypass

text: Aside from the differences in location, venous cannulation is performed similarly to arterial cannulation. Since calcification of the venous system is less common, the inspection or use of an ultrasound for calcification at the cannulation sites is unnecessary. Also, because the venous system is under much less pressure than the arterial system, only a single suture is required to hold the cannula in place. If only a single cannula is to be used (dual-stage cannulation), it is passed through the right atrial appendage, through the tricuspid valve, and into the inferior vena cava. If two cannula are required (single-stage cannulation), the first one is typically passed through the superior vena cava and the second through the inferior vena cava. The femoral vein may also be cannulated in select patients.


title: Cardiopulmonary bypass

text: If the heart must be stopped for the operation, cardioplegia cannulas are also required. Antegrade cardiopledgia (forward flowing, through the heart's arteries), retrograde cardiopledgia (backwards flowing, through the heart's veins), or both types may be used depending on the operation and surgeon preference. For antegrade cardiopledgia, a small incision is made in the aorta proximal to the arterial cannulation site (between the heart and arterial cannulation site) and the cannula is placed through this to deliver cardiopledgia to the coronary arteries. For retrograde cardiopledgia, an incision is made on the posterior (back) surface of the heart through the right ventricle. The cannula is placed in this incision, passed through the tricuspid valve, and into the coronary sinus. The cardiopledgia lines are connected to the CPB machine.


title: Cardiopulmonary bypass

text: At this point, the patient is ready to go on bypass. Blood from the venous cannula(s) enters the CPB machine by gravity where it is oxygenated and cooled (if necessary) before returning to the body through the arterial cannula. Cardiopledgia can now be administered to stop the heart, and a cross-clamp is placed across the aorta between the arterial cannula and cardiopledgia cannula to prevent the arterial blood from flowing backwards into the heart.


title: Cardiopulmonary bypass

text: Once the patient is ready to come off of bypass support, the cross-clamp and cannulas are removed and protamine sulfate is administered to reverse the anticoagulative effects of heparin.


title: Cardiopulmonary bypass

text: The Austrian-German physiologist Maximilian von Frey constructed an early prototype of a heart-lung machine in 1885 at Carl Ludwig's Physiological Institute of the University of Leipzig.


title: Cardiopulmonary bypass

text: However, such machines were not feasible before the discovery of heparin in 1916, which prevents blood coagulation. The Soviet scientist Sergei Brukhonenko developed a heart-lung machine for total body perfusion in 1926 named the "Autojektor", which was used in experiments with canines. A team of scientists at the University of Birmingham (including Eric Charles, a chemical engineer) were among the pioneers of this technology.


title: Cardiopulmonary bypass

text: Dr. Clarence Dennis led the team at the University of Minnesota Medical Center that on April 5, 1951, conducted the first human operation involving open cardiotomy with temporary mechanical takeover of both heart and lung functions. The patient did not survive due to an unexpected complex congenital heart defect. One member of the team was Dr. Russell M. Nelson, who later became president of the Church of Jesus Christ of Latter-day Saints and who performed the first open heart surgery in Utah.


title: Cardiopulmonary bypass

text: The first successful mechanical support of left ventricular function was performed on July 3, 1952, by Forest Dewey Dodrill using a machine co-developed with General Motors, the Dodrill-GMR. The machine was later used to support right ventricular function.


title: Cardiopulmonary bypass

text: The first successful open heart procedure on a human utilizing the heart lung machine was performed by John Gibbon and Frank F. Allbritten, Jr. on May 6, 1953, at Thomas Jefferson University Hospital in Philadelphia. They repaired an atrial septal defect in an 18-year-old woman. Gibbon's machine was further developed into a reliable instrument by a surgical team led by John W. Kirklin at the Mayo Clinic in Rochester, Minnesota in the mid-1950s.


title: Cardiopulmonary bypass

text: The oxygenator was first conceptualized in the 17th century by Robert Hooke and developed into practical extracorporeal oxygenators by French and German experimental physiologists in the 19th century. Bubble oxygenators have no intervening barrier between blood and oxygen, these are called 'direct contact' oxygenators. Membrane oxygenators introduce a gas-permeable membrane between blood and oxygen that decreases the blood trauma of direct-contact oxygenators. Much work since the 1960s focused on overcoming the gas exchange handicap of the membrane barrier, leading to the development of high-performance microporous hollow-fibre oxygenators that eventually replaced direct-contact oxygenators in cardiac theatres.


title: Cardiopulmonary bypass

text: In 1983, Ken Litzie patented a closed emergency heart bypass system which reduced circuit and component complexity. This device improved patient survival after cardiac arrest because it could be rapidly deployed in non-surgical settings.


title: Chest hair

text: Chest hair is hair that grows on the chest in the region between the neck and the abdomen. Chest hair develops during and after puberty along with other types of androgenic hair.


title: Chest hair

text: Although vellus hair is already present in the area in childhood, chest hair is the terminal hair that develops as an effect of rising levels of androgens (primarily testosterone and its derivatives) due to puberty. Different from the head hair, it is therefore a secondary sexual characteristic. Men tend to be covered with far more terminal hair, particularly on the chest, the abdomen, and the face.


title: Chest hair

text: The development of chest hair begins normally during late puberty, usually between the ages of 12 and 18. It can also start later, between the age of 20 and 30, so that many men in their twenties have not yet reached their full chest hair development. The growth continues subsequently.


title: Chest hair

text: The individual occurrence and characteristics of chest hair depend on the genetic disposition, the hormonal status and the age of the person. The genes primarily determine the amount, patterns and thickness of chest hair. Some men are very hairy, while others have no chest hair at all. All ranges and patterns of hair growth are normal. The areas where terminal hair may grow are the periareolar areas (nipples), the centre and sides of the chest and the clavicle collarbone.


title: Chest hair

text: The direction of growth of hair can make for interesting patterns, akin to depictions of mathematical vector fields. Typical males will exhibit a node on the upper sternum, the hair above which points up and the hair below which points down. Some individuals have spirals on their upper pectoral regions (several inches from the nipple towards the neck) which run clockwise on the left breast and counter-clockwise on the right.


title: Chest hair

text: Considering an individual occurrence of chest hair as abnormal is usually not due to medical indications but primarily to cultural and social attitudes. An excessive growth of terminal hair on the body of men and women is called hypertrichosis. This medical term has to be distinguished from hirsutism that just affects women. These women can develop terminal hair on the chest following the male pattern as a symptom of an endocrine disease.


title: Chest hair

text: There have been occasional studies documenting patterns of chest hair in men and occurrence of these patterns. A study of 1,400 white men aged 17 to 71 conducted by L.R. Setty in the 1960s defines 15 patterns of chest hair. In this study, four parts of the chest in which terminal hair occurs were identified:


title: Chest hair

text: Chest hair may occur on each of these areas independent from the others, making for a total of 15 combinations in addition to the "apilose" (bare) pattern. Hair is said to occur on both the pectoral and circumareolar areas when there is hair around the nipples and on the breast, but these areas are not connected.


title: Chest hair

text: The "pecto-sterno-infraclavicular" pattern, in which the breast, sternum and medial end of the clavicle is covered with terminal hair, is most common (57%).


title: Yumi

text: The was an important weapon of the samurai warrior during the feudal period of Japan. It is typically shot with Japanese arrows known as .


title: Yumi

text: The most famous style of is an asymmetrically shaped long bow with a length of more than , characterized by the archer holding the part of the bow below the center to shoot the arrow.


title: Yumi

text: Most of the excavated Jōmon period () bows are in length, while most of the Yayoi period () bows are in length. The bows in these periods were made from a single processed wood, and the bows with this structure were called and were used until the Nara period (710–794 CE). It is unknown when the asymmetrical came into use, but the first written record is found in the "Book of Wei", a Chinese historical manuscript dating to the 3rd century CE, which describes the people of the Japanese islands using "spears, shields, and wooden bows for arms; the wooden bows are made with the lower limbs short and the upper limbs long; and bamboo arrows with points of either iron or bone." The oldest asymmetrical found to date was discovered in Nara Prefecture, and is estimated to be from the 5th century.


title: Yumi

text: Some of the bows found as burial goods in (ancient tombs) during the Kofun period (300–538 CE) were decorated with gold or silver, and it is believed that they were also used in ceremonies. The length of most bows in this period ranged from , and it is thought that they were powerful enough to shoot enemies and animals at close range.


title: Yumi

text: In the Nara period, lacquered bows with more weather resistance and decorative features appeared. "Euonymus hamiltonianus", "Zelkova serrata", and "Toxicodendron succedaneum", which are highly elastic wood, came to be used for making , and many became as long as roughly 7 3 (), increasing their power and range. Since then, the structure of the bow has gradually evolved, but its length of roughly 7 3 has been passed down to the present day.


title: Yumi

text: From the mid to late Heian period (794–1185), the Japanese developed the style of , the first in Japan with a laminated structure. This style of was made by attaching bamboo to a wooden with a flat front side using glue made from a fish float, and the elasticity of the bamboo improved the bow's range, power and durability. Nasu no Yoichi was famous as a master of archery in the late Heian period; his fame was depicted in "The Tale of the Heike" and , and he was the subject of various Japanese traditional performing arts and fine arts such as Noh, , , kabuki, and ukiyo-e of later generations.


title: Yumi

text: From the end of the Heian period to the beginning of the Kamakura period (1185–1333), the was developed, and bamboo was glued not only on the front side but also on the reverse side of the . In the late Kamakura period, the shape of the bow became more asymmetrical, with the upper part bent from the lower part, so that it resembled a modern bow, further increasing the range and power of the .


title: Yumi

text: From the middle of the Heian period, the style of , in which wisteria was wrapped around a laminated-structure to improve its elasticity and sturdiness, became popular. The style in particular was the strongest weapon of the Kamakura period, with a maximum range of and an effective range of that could inflict fatal wounds on targets. There are more than 20 varieties of , depending on how and where on the bow the wisteria is wound. In the Muromachi period (1336–1573), the went from its luxurious exterior to a piece of equipment that symbolized the rank of commander.


title: Yumi

text: During the Kamakura period, when the samurai class came to power, (archery) became more and more popular, especially the three types of mounted archery: , , and .


title: Yumi

text: The was developed during the Muromachi period, and bamboo was used on the side of the bow to increase its range and power.


title: Yumi

text: During the Sengoku period (1467–1615), the used in modern was developed, completing the original form of the Japanese bow now known around the world. The characteristic of the bow is that it has a greatly changed laminated structure from the conventional bow. The core of the structure is about four pieces of bonded bamboo, with bamboo glued to the front side and the other side and wood glued to the sides. This improved the range and power of the bow and enabled it to shoot through targets away in the Sanjusangen-do archery contest, , a famous event still held today. Research on (arrowheads) was actively conducted to enhance their killing ability, and of various shapes were developed. During this period, the was mass-produced by Japanese swordsmiths, and mobilized (foot soldiers) used them to exert tremendous power on the battlefield. However, because took a long time to load, were inconvenient in rainy weather when damp gunpowder would not fire, and were not exactly subtle in terms of noise, the did not go out of fashion and continued to be used as an important military force on the battlefield.


title: Yumi

text: When Japanese society became more peaceful in the Edo period (1603–1867), the spirituality and decorativeness of the became important, and developed as a samurai's way of doing things.


title: Yumi

text: Even today, the is used in and ceremonies, and in Grand sumo tournaments, a ceremony called the , which is dedicated to Shinto , is held.


title: Yumi

text: The is exceptionally tall, standing over in height, and typically surpasses the height of the . They are traditionally made by laminating bamboo, wood and leather, using techniques which have not changed for centuries, although some archers (particularly beginners) may use a synthetic .


title: Yumi

text: The is asymmetrical; according to the All Nippon Kyudo Federation, the grip () has to be positioned at about two thirds of the distance from the upper tip.


title: Yumi

text: The upper and lower curves also differ. Several hypotheses have been offered for this asymmetric shape. Some believe it was designed for use on a horse, where the could be moved from one side of the horse to the other with ease; however, there is evidence that the asymmetrical shape predates its use on horseback.


title: Yumi

text: Others claim that asymmetry was needed to enable shooting from a kneeling position. Yet another explanation is the characteristics of the wood from a time before laminating techniques. In case the bow is made from a single piece of wood, its modulus of elasticity is different between the part taken from the treetop side and the other side. A lower grip balances it.


title: Yumi

text: The hand holding the may also experience less vibration due to the grip being on a vibration node of the bow. A perfectly uniform pole has nodes at 1/4 and 3/4 of the way from the ends, or 1/2 if held taut at the ends – these positions will change significantly with shape and consistency of the bow material.


title: Yumi

text: The string of a , a , is traditionally made of hemp, although most modern archers will use strings made of synthetic materials such as Kevlar, which will last longer.


title: Yumi

text: Strings are usually not replaced until they break; this results in the flexing in the direction opposite to the way it is drawn, and is considered beneficial to the health of the .


title: Yumi

text: The nocking-point on the string is built up through the application of hemp and glue to protect the string and to provide a thickness which helps hold the nock ( of the arrow, a , in place while drawing the . However, it can also be made of strands of waxed bamboo.


title: Yumi

text: A bamboo requires careful attention. Left unattended, the can warp out of shape and may eventually become unusable. The shape of a will change through normal use and can be re-formed when needed through manual application of pressure, through shaping blocks, or by leaving it strung or unstrung when not in use.


title: Yumi

text: The shape of the curves of a is greatly affected by whether it is left strung or unstrung when not in use. The decision to leave a strung or unstrung depends upon the current shape of the . A that is relatively flat when unstrung will usually be left unstrung when not in use (a in this state is sometimes referred to as being 'tired'). A that has excessive curvature when unstrung is typically left strung for a period of time to 'tame' the .


title: Serket

text: Serket () is the goddess of healing venomous stings and bites in Egyptian mythology, originally the deification of the scorpion. Her family life is unknown, but she is sometimes credited as the daughter of Neith and Khnum, making her a sister to Sobek and Apep.


title: Serket

text: Scorpion stings lead to paralysis and Serket's name describes this, as it means "(she who) tightens the throat"; however, Serket's name also can be read as meaning "(she who) causes the throat to breathe" and so, as well as being seen as stinging the unrighteous, Serket was seen as one who could cure scorpion stings and the effects of other venoms such as snakebites.


title: Serket

text: In the art of ancient Egypt, Serket was depicted as a scorpion (a symbol found on the earliest artifacts of the culture, such as from Naqada III) or to have the body of a scorpion but the head of a woman or as a woman with a scorpion on her head. Although Serket does not appear to have had any temples, she had a sizable number of priests in many communities.


title: Serket

text: One of the most dangerous species of scorpion, the deathstalker ("Leiurus quinquestriatus") resides in North Africa and its sting may kill, so Serket was considered a highly important goddess and sometimes she was considered by pharaohs to be their patron. Her close association with the early rulers implies that she was their protector, notably Scorpion I and Scorpion II.


title: Serket

text: As the protector against venom and snakebite, Serket often was said to protect the deities from Apep, the great snake-demon of evil, sometimes being depicted as the guard when Apep was captured.


title: Serket

text: As many of the venomous creatures of Egypt could prove fatal, Serket also was considered a protector of the dead, particularly being associated with venoms and fluids causing stiffening. She was thus said to be the protector of the tents of embalmers and of the canopic jar associated with venom—the jar of the intestine—which was deified later as Qebehsenuef, one of the four sons of Horus.


title: Serket

text: As the guard of one of the canopic jars and a protector, Serket gained a strong association with Neith, Isis, and Nephthys, who also performed similar functions. Eventually, Serket began to be identified with Isis, sharing imagery and parentage, until finally, Serket was said to be merely an aspect of Isis, whose cult had become dominant.


title: Serket

text: It has been suggested that Serket's identification with a scorpion may be a misinterpretation of the determinative of her name and animal associated with her and that could refer not to a scorpion, but rather to a water scorpion (Nepidae). According to this hypothesis, Serket is referred to as "she who gives breath" because of the way water scorpions seem to breathe underwater. The appearance of a waterscorpion must have made it be associated with the scorpion, therefore the use of the goddess for curing scorpion stings and other venomous creatures or maybe exactly because she "causes to breathe", not for the physical similarities of the creatures.


title: KitchenAid

text: KitchenAid is an American home appliance brand owned by Whirlpool Corporation. The company was started in 1919 by The Hobart Manufacturing Company to produce stand mixers; the "H-5" was the first model introduced. The company faced competition as rivals moved into this emerging market, and introduced its trademarked silhouette in the 1930s with the model "K", the work of designer Egmont Arens. The brand's stand mixers have changed little in design since, and attachments from the model "K" onwards are compatible with the modern machines.


title: KitchenAid

text: Dishwashers were the second product line to be introduced, in 1949. A late 1980s promotional campaign on the back of an expansion by retailer Williams Sonoma saw brand awareness double in three years.


title: KitchenAid

text: The idea of a stand mixer was formulated by Herbert Johnston, an engineer working at the Hobart Corporation. He had been inspired after seeing a baker mix dough, and thought that there must be a better way of doing the task. In 1914, development began, and soon the model "H" mixer was launched for industrial work. The U.S. Navy ordered mixers for two new , and , as well as the U.S. Navy's first dreadnought battleship, . In 1917, Hobart stand mixers became standard equipment on all U.S. Navy ships, prompting development to begin on the first home models.


title: KitchenAid

text: The first machine to carry the KitchenAid name was the ten-quart C-10 model, introduced in 1918 and built at Hobart's "Troy Metal Products" subsidiary in Springfield, Ohio. Prototype models were given to the wives of factory executives, and the product was named when one stated "I don't care what you call it, but I know it's the best kitchen aid I've ever had!" They were initially marketed to the farmhouse kitchen and were available in hardware stores. But owing to


title: KitchenAid

text: the difficulty in convincing retailers to take up the product, the company recruited a mostly female sales force, which sold the mixers door-to-door. The C-10 machine was also marketed heavily toward soda fountains and small commercial kitchens, and was also sold under the "FountainAid" and "BakersAid" model names.


title: KitchenAid

text: In 1922, KitchenAid introduced the H-5 mixer as its new home-use offering. The H-5 mixer was smaller and lighter than the C-10, and had a more manageable five-quart bowl. The model "G" mixer, about half the weight of the "H-5" was released in August 1928. In the 1920s, several other companies introduced similar mixers, and the Sunbeam Mixmaster became the most popular among consumers until the 1950s.


title: KitchenAid

text: KitchenAid mixers remained popular, and in the late 1930s, the factory would completely sell out its products each Christmas. The factory was closed for the duration of World War II. After the war, production started up again in 1946 when the factory moved to Greenville, Ohio, to expand capacity. The product range expanded beyond stand mixers for the first time in 1949, when dishwashers were introduced.


title: KitchenAid

text: In 1985, the company purchased the Chambers Company to incorporate its range of cookers into the KitchenAid brand. After being cleared by a Federal appeals court in January 1986, Whirlpool Corporation was cleared to purchase KitchenAid for $150 million, after initial complaints regarding competition from dishwasher manufacturers White Consolidated Industries and Magic Chef were dismissed. Refrigerators were added to the product line later in 1986. The company used the popularity of celebrity chefs during the late 1980s to seize the chance to expand its customer range. In 1988, retailer Williams Sonoma was opening new stores across the United States and released a cobalt blue stand mixer for the company. Although the retailer had been carrying KitchenAid products since 1959, the new stores introduced the mixers to a wider range of home cooks. This combined with a change in marketing strategy for KitchenAid, which resulted in a doubling of brand awareness over the course of the following three years.


title: KitchenAid

text: KitchenAid began manufacturing blenders and other small appliances in the mid-1990s. The brand was further promoted by sponsoring the PBS show "Home Cooking", and by introducing the mixers to television chefs such as Julia Child and Martha Stewart. Following the success with Williams Sonoma, specific points of purchase were set up in department stores such as Kohl's and Macy's. Specific color mixers were released for specific retailers or to benefit charities, such as a pink mixer released to raise funds for breast cancer research or mixers sold at Target stores being available in that company's signature shade of red. The ProLine range of appliances was launched in 2003 with an initial six-month exclusivity agreement with Williams Sonoma.


title: KitchenAid

text: Egmont Arens was hired in the 1930s to design a low-cost series of mixers. This resulted in the production of the KitchenAid Model "K" which featured a streamlined profile for the first time, and the KitchenAid standard design has remained relatively unchanged since then. The silhouette has since been made a registered trademark with the U.S. Patent and Trademark Office. In 1997 the San Francisco Museum of Modern Art selected the KitchenAid stand mixer as an icon of American design. There is an attachment hub on the front of each mixer. Every KitchenAid mixer since the introduction of the Model "K" has allowed for cross-generational attachment compatibility, meaning that attachments from the 1930s can be used on modern mixers, and vice versa. This cross-generational compatibility extends only to attachments powered through the hub. Other accessories (beaters, bowls, etc.) are not necessarily compatible even across similar models in production at the same time (for example, not all current production six-quart bowl-lift mixers use the same accessories). Initially the mixers were only available in white; a range of four colors was introduced in 1955.


title: KitchenAid

text: Today, some KitchenAid products are manufactured in Ohio, South Carolina, Iowa, Mississippi, Indiana, Arkansas, Ontario, and Quebec while others are manufactured in China, and its appliances are distributed throughout North America. All KitchenAid stand mixers are assembled in its factory in Greenville, Ohio. The die-cast parts of the machines come from various manufacturing plants around the world. A factory tour, known as the "KitchenAid Experience" is conducted by the assembly line workers.


title: KitchenAid

text: In March 2016, KitchenAid announced that it would offer a line of food mixes with a Michigan food company, Franzese USA, Inc. In their press release, KitchenAid states, “Considering that tens of millions of American kitchens are outfitted with our stand mixers, we’re confident that these mixers will become a staple in many pantries.”


title: Suzuki Celerio

text: The Suzuki Celerio is a hatchback city car produced by the Japanese manufacturer Suzuki since 2008. Originally a rebadged Alto/A-Star city car for some markets, the Celerio was made as a global nameplate and a standalone model replacing the A-Star in 2014. Suzuki unveiled the second-generation Celerio at the Auto Expo 2014 in India, after being previewed as the A:Wind concept model at the Thailand International Motor Expo in November 2013. The third-generation model was unveiled in November 2021.


title: Suzuki Celerio

text: Prior to being developed as a standalone model from the second generation onwards, the "Celerio" nameplate was first used for the rebadged Alto/A-Star in some markets between 2008 and 2013.


title: Suzuki Celerio

text: The second-generation Celerio was launched in India as a standalone model with six variants. The diesel version of Celerio was introduced in the second quarter of 2015. The hatchback is currently available in petrol and CNG fuel options. The Celerio X is a premium variant of Celerio with a sportier look, equipped with AGS technology, Striking X graphic and grille design.


title: Suzuki Celerio

text: The petrol engine is a Suzuki K-series K10B latest revision called K-Next (not same as Wagon R K10B, because Wagon R has compression ratio of 10:1 while Celerio/Cultus has 11:1). The gearbox is basically a manual transmission with a transmission control unit (TCU) that actuates the hydraulics to shift the gears.


title: Suzuki Celerio

text: It was launched on the European market in the second half of 2014, having its European premiere at the Geneva Motor Show in March 2014. However, the British, Irish, Australian and New Zealand market (ceased being built for UK/IE market in 2019, 2021 for Australasia) were produced in the Suzuki's Rayong manufacturing plant in Thailand. The Australasian market model lacked a fifth seatbelt.


title: Suzuki Celerio

text: The Pakistani version of the Celerio (Cultus in Pakistan) was launched approximately a year after Previous Generation of Cultus was discontinued due to low sales. Pak Suzuki launched Cultus in three variants: VXR, VXL and VXL AGS. VXR and VXL had major differences, VXR did not come installed with Airbags, Fog lights, Alloy wheels, Immobilizer, Chrome grille, Body Colored door handles and Wing mirrors, while VXL was offered with these features. later in 2020, Sat-Nav was also available on VXL models. VXL AGS was basically the Automatic version of the VXL variant. 1.0 litre engine was the only option offered.


title: Suzuki Celerio

text: Pakistani version of Celerio was launched under Cultus nameplate. It was offered under Celerio name by Maruti Suzuki in India and Suzuki Motor Thailand in Rayong Province Thailand. It replaces the A-Star and Zen Estilo. The Celerio was Pakistan's first car with AutoGear Shift technology.


title: Suzuki Celerio

text: The India version of the Celerio was awarded zero stars by the Global NCAP after a test conducted in May 2016 (similar to Latin NCAP 2013). The basic version of the Celerio in India and Pakistan does not include airbags nor ABS and the body shell of the vehicle was rated by the Global NCAP as "unstable".


title: Suzuki Celerio

text: The European Suzuki Celerio scored 3 of 5 stars when tested by Euro NCAP in 2014 (similar to Latin NCAP 2020) and 4 of 5 by ANCAP in 2015. ANCAP and Euro NCAP received criticism claiming they underscored the Celerio relative to other cars that had fewer airbags or performed worse in crash tests.


title: Suzuki Celerio

text: Maruti Suzuki introduced its all new 793 cc diesel engine in the Celerio on 3 June 2015, at a price of INR 4.65 lacs. The Celerio DDiS125 is powered by Suzuki’s first indigenously developed two-cylinder motor which delivers of max power and 125 Nm of peak torque. It also promises to deliver a segment best mileage of .


title: Suzuki Celerio

text: Externally, the Celerio diesel is identical to its petrol version. The Celerio diesel variant was discontinued in February 2017.


title: Suzuki Celerio

text: The third-generation Celerio was unveiled in India on 10 November 2021. The car is built on lightweight HEARTECT platform that also underpins Wagon R and Ignis. It is powered with a 1.0-liter "K10C Dualjet" engine which is a reworked "K10B" engine with dual fuel injectors per cylinder, VVT and several other modifications.


title: The Widow (TV series)

text: The Widow is a British television drama series created and written by Harry and Jack Williams, airing on both British ITV and American streaming service Amazon Prime Video, with Prime also carrying the series internationally. It stars Kate Beckinsale as a woman who believes that her husband was killed in a plane crash three years earlier, but then discovers that he is still alive in the Congo. The show was released on Amazon Prime Video on 1 March 2019 before being broadcast on ITV from 8 April 2019.


title: The Widow (TV series)

text: The series follows Georgia Wells (Kate Beckinsale) whose husband Will died in a plane crash on a trip to the Congo in Africa. Three years later, she sees a man resembling him on a news story reporting civil unrest in the Democratic Republic of the Congo, and she travels to Kinshasa to uncover the truth. She starts to look for answers, particularly why her husband evidently faked his own death. The eight-episode series features multiple story lines and explores themes such as violence and corruption.


title: The Widow (TV series)

text: "The Widow" is a co-production of British ITV and Amazon Video. It was filmed in South Africa, Wales, and Rotterdam. The heat in some of the locations became difficult for Beckinsale, who was hospitalised after passing out while shooting a scene.


title: The Widow (TV series)

text: On Rotten Tomatoes season 1 has an approval rating of 56% based on reviews from 27 critics. The site's consensus states: Ferociously ambitious, "The Widow" boasts Kate Beckinsale's killer action chops but goes astray in a jungle of problematic tropes and unsatisfying twists.


title: Steamboy

text: In 1863, where an alternate nineteenth century Europe has made tremendous strides in steam-powered technologies, scientist Lloyd Steam and his son, Edward “Eddy” Steam, have succeeded in discovering a pure mineral water in Iceland which they believe can be harnessed as a nearly unlimited power source for steam engines. An experiment in Russian Alaska goes terribly wrong, with Eddy being engulfed in freezing gases, but results in the creation of a spherical device.


title: Steamboy

text: Three years later, Lloyd sends the device, along with its schematics, to his grandson (and Eddy’s son), James Ray Steam, who works as a maintenance boy in Manchester, England, along with instructions to guard it. Members of "The O'Hara Foundation" arrive and attempt to steal the sphere, but Lloyd appears, stating that the device killed Eddy and bids James to flee and deliver the device to Robert Stephenson. After fleeing the O'Hara agents on his personal steam-powered monowheel, James briefly meets Stephenson on a train headed into Manchester, but James, along with the device, are captured by O'Hara agents in a dirigible.


title: Steamboy

text: James is taken to London, where preparations are being made for the 1866 Great Exhibition, and meets Scarlett O'Hara St Jones, the spoiled granddaughter of the Foundation's head chairman, Archibald Simon O’Hara. He also discovers Eddy, alive but severely scarred and mechanized from his injuries in Alaska, working with O'Hara on the "Steam Castle"; an elaborate facility entirely powered by three devices called "Steam Balls," one of which was the device sent to James. James is enamored both by the castle, and his father's vision of using it to enlighten mankind, and volunteers to help complete the project. He also begins developing a love/hate friendship with Scarlett, who is attracted to him.


title: Steamboy

text: James encounters Lloyd again, who was captured by O'Hara, but has escaped from his cell and is attempting to sabotage the castle, revealing that the Foundation's true intentions for the exhibition is to sell weapons of war. Lloyd shows James a hidden armory filled with massive steam-powered war machines built by Eddy, and James struggles with the moral dichotomy of being a scientist - of how to contribute to the world without giving into vanity, leaving him conflicted as to whether to side with Lloyd or Edward, who themselves have become estranged.


title: Steamboy

text: Lloyd and James reach the core of the castle and remove one of the Steam Balls, but Lloyd is shot and recaptured by O'Hara, as James escapes with the device. The next morning, the exhibition is underway, and James brings the ball to Stephenson, giving him the ball and the knowledge he acquired in captivity. The British military attempts to arrest Eddy, but Eddy unleashes his steam powered weapons on the soldiers, turning the exhibition into a battlefield. When Stephenson uses the Steam Ball to enhance his own company's tanks, James realizes that he had no better intentions than the Foundation.


title: Steamboy

text: Eager to show the world the castle's true power, Eddy orders it to be prematurely activated, causing the structure to rise and shed its decorative outer shell, revealing it to be a monstrous floating fortress. As the Royal Navy and Stephenson attempt to defend London from the floating fortress, James steals the Steam Ball back and uses it to create a makeshift aircraft to re-board the fortress. James meets Eddy, Scarlett, and Lloyd in the castle's control room, where Lloyd confronts Eddy about his actions, before shooting him in a fit of rage, but Eddy falls into a cloud of steam and disappears.


title: Steamboy

text: With the castle steered off course, the structure has become unstable and threatens to explode over the city. As Lloyd and James rush to redirect the castle over the Thames, Eddy, whose metal body repelled the gunshot, re-emerges from the steam and assists them, having realized his folly. James re-installs the stolen steam ball, and makes his way to the control room to make a final escape with Scarlett on an emergency jetpack, while Eddy and Lloyd reconcile and halt the machine over the river and escape as well. The castle detonates in a spectacular explosion, sparing the city from destruction.


title: Steamboy

text: The ending montage reveals James returning home, and later becoming a global superhero using the jetpack gear from the castle; Lloyd introducing James to electricity and finally passing away; Eddy founding a corporate conglomerate; Scarlett maturing and becoming a famous pilot, and the Great War being fought with paratroopers and zeppelins.


title: Steamboy

text: Katsuhiro Otomo first completed a proposal of "Steamboy" as an original video animation of three 40-minute episodes on June 30, 1994. The pilot storyboard was completed in July of the following year.


title: Steamboy

text: The film was in production for ten years and utilized more than 180,000 drawings and 440 CG cuts. It had a production budget of , then equivalent to . This made it the most expensive Japanese anime film up until then, surpassing Otomo's "Metropolis" (2001).


title: Steamboy

text: The Japanese release of "Steamboy" featured the voices of Anne Suzuki, Manami Konishi and Masane Tsukayama. The United States release, held in a limited number of U.S. theaters on March 18, 2005, and expanded to additional theaters on March 25, was released in two formats: a subtitled release featured in fewer cinemas, and an English dubbed version cut down by 15 minutes that featured the voices of Anna Paquin, Alfred Molina, and Patrick Stewart.


title: Steamboy

text: "Steamboy" was distributed across Japan by Toho and English regions by Sony's Triumph Films subsidiary. The VHS and DVD was released in Japan on April 15, 2005, in Australia on June 22, 2005, the USA on July 26, 2005, and the UK on March 27, 2006. Both the edited English version and the original Japanese version were made available on DVD, with the longer version being sold as the "Director's Cut".


title: Steamboy

text: The UK Blu-Ray/DVD combo version of the film is the original, full length version. However, it has been misprinted as the cut down version of the film.


title: Steamboy

text: "Steamboy" was later adapted into a video game for the PlayStation 2 in Japan by Bandai. (Development by Cavia and SIMS)


title: Steamboy

text: "Steamboy" was released in Japan on July 17, 2004 alongside "" where it was distributed by Toho. The film was released in the United States by Triumph Films with an English-language dub on March 18, 2005, prior to this, TriStar Pictures was going to release the movie. The film was released to home video with the original Japanese version with English subtitles.


title: Steamboy

text: In Japan, the film grossed , making it the 18th highest-grossing domestic film of 2004. The film was not a box office success in the United States, where it grossed $468,867 in 2005.


title: Steamboy

text: According to the reviewer KJB at IGN.com, this could be due to the marketing methods used in the United States. "Steamboy" could have had a larger Western audience, but due to the limited release, that was not able to happen. ""Steamboy" is one of those few anime films that would be able to play to a wide audience in the United States. Instead, the film is getting a limited release through Sony's smaller label, skipping some cities entirely and only playing in smaller art houses in many of the cities that are getting the film."


title: Steamboy

text: "Steamboy" was the 2004 recipient of Best Animated Feature Film at the Sitges - Catalan International Film Festival. The film received overall positive reviews from critics.


title: Steamboy

text: Stephen Hunter of "The Washington Post" states, "The movie never transcended its elaborate production work to achieve an independent reality. It's simply pictures of what could have happened."


title: Steamboy

text: Review aggregation website Rotten Tomatoes gave "Steamboy" a rating of 59% based on 91 reviews, with the site's consensus "The story isn't the greatest, but there's an abundance of sci-fi eye candy to compensate."


title: Chicken curry

text: Chicken curry is a dish originating from the Indian subcontinent. It is common in the Indian subcontinent, Southeast Asia, Great Britain, Caribbean, and Japan. A typical curry from the Indian subcontinent consists of chicken stewed in an onion- and tomato-based sauce, flavoured with ginger, garlic, tomato puree, chilli peppers and a variety of spices, often including turmeric, cumin, coriander, cinnamon, and cardamom. Outside of South Asia, chicken curry is often made with a pre-made spice mixture known as curry powder.


title: Chicken curry

text: Indian cuisine has a large amount of regional variation, with many variations on the basic chicken curry recipe. Indian chicken curry typically starts with whole spices, heated in oil. A sauce is then made with onions, ginger, garlic, and tomatoes, and powdered spices. Bone-in pieces of chicken are then added to the sauce, and simmered until cooked through. In south India, coconut and curry leaves are also common ingredients. Chicken curry is usually garnished with coriander leaves, and served with rice or roti.


title: Chicken curry

text: This dish was introduced to the Caribbean by indentured Indian girmitya workers. At that time, the dish was very similar to the chicken curry dish of India, consisting mostly of sauce with few chicken pieces. However, poultry in Trinidad and Tobago was so readily available, the dish began consisting of mainly chicken, flavored with curry spices. Typical preparation include washing and then seasoning and marinating the chicken meat in a green seasoning consisting of bandhania, dhania, pudina, thyme, scallion, onion, garlic, and peppers. Then the curry is prepared by first adding oil to the pot and then adding the phoran, which in the Caribbean consist of caripoulé, cut-up onions, peppers, and tomatoes, and garlic paste (some add ginger too). Some may also add saunf, jeera and meethi seeds along with the phoran. Then Madras curry powder (some also additionally add garam masala or any other masala they wish), mixed with water and green seasoning is added to the pot and fried up with the phoran in the oil, in a process known as "bunjay" or "bujna". Then the marinated chicken is added to the pot and salt, black pepper, and sometimes roasted jeera powder is added. At this point aloo, pigeon peas, channa, or baigan is sometimes added. Then it is left to cook for 15–20 minutes on medium heat. Afterwards, water (some additionally add coconut milk) is added to make the "soorwah" or sauce/gravy and it is brought to a boil on lower to medium heat for 5–10 minutes. It is usually served with paratha or dalpuri roti or with dal bhat (dal and rice). Curry chicken and its derivatives are also popular in Suriname, Guyana, Jamaica, and other Caribbean territories with Indian and South Asian influence.


title: Chicken curry

text: In Southeast Asia, where coconuts, and different spices originated, various native dishes made with coconut milk or curry pastes and eaten with rice are often collectively referred to as "curries" in English. Examples of these include Cambodian "kari sach moan", Thai "gaeng gai" and Filipino "ginataang manok". Chicken curries feature prominently in the repertoire of Burmese curries and in Burmese "ohn no khao swè", a noodle soup of coconut milk and curried chicken.


title: Chicken curry

text: However, derivatives of Indian chicken curry may be distinguished because they are relatively modern and are made with curry powder, curry tree leaves, or other Indian spices, like the Filipino chicken curry and the Malaysian chicken curry, although they still use ingredients native to Southeast Asia.


title: Chicken curry

text: Country captain chicken is a stewed chicken dish flavored with curry powder, popular in parts of the Southern United States. The "Hobson-Jobson Dictionary" states the following:


title: Chicken curry

text: This dish dates back to the early 1800s. A British sea captain stationed in Bengal, India, shared the recipe for this dish with some friends at the major shipping port in Savannah, Georgia.


title: Chicken curry

text: In 1940, Mrs. W.L. Bullard from Warm Springs, Georgia served this dish under the name "Country Captain" to Franklin D. Roosevelt (the 32nd president of the United States of America) and to General George S. Patton (a distinguished U.S. Army General). Their warm praise and keen liking and love of this dish were factors in reforging the Southern United States classic status. Roosevelt was so fond of Warm Springs, Georgia, that he built his only self-owned home in Warm Springs. It was a medium-sized, six room cottage, that he liked to call "The Little White House".


title: Valentina (drag queen)

text: James Andrew Leyva (born May 14, 1991), better known by the stage name Valentina, is an American drag performer, actor, television personality and singer who came to international attention as a contestant on the ninth season of "RuPaul's Drag Race" and the fourth season of "RuPaul's Drag Race All Stars".


title: Valentina (drag queen)

text: Valentina was born in Bell, California to Mexican parents, and began working as a professional drag queen around ten months before filming "RuPaul's" "Drag Race," although they already had a background in fashion and the performing arts. Leyva chose to go by "Valentina" in drag after the hot sauce of the same name. Valentina is known for using her drag as a way to represent Latin American culture on stage and make drag more accepted in Latin American culture.


title: Valentina (drag queen)

text: In 2015, Valentina won an early club version of the Boulet Brothers' "Dragula" contest", a precursor of the television show.


title: Valentina (drag queen)

text: On February 2, 2017, Valentina was announced as one of fourteen contestants competing for the ninth season of "RuPaul's Drag Race". She was eliminated in episode nine to Nina Bo'Nina Brown after infamously losing a lipsync battle to "Greedy" by Ariana Grande; she was reluctant to take off a mask covering her mouth as she did not know the lyrics to the song, a moment which went viral across social media. She placed seventh overall, and their elimination sparked some controversy online as she was popular with fans. She was later voted as "Miss Congeniality" by the viewers of the show, but was mockingly dubbed "Fan Favorite" by her castmates, due to their view that she was unsuitable for a congenial title. During the season 10 finale, Valentina appeared via a pre-recorded video message to crown her successor for the Miss Congeniality title, Monét X Change.


title: Valentina (drag queen)

text: Outside of "Drag Race", Valentina appeared in the sixth episode of the twenty-fourth season of "America's Next Top Model", in a photo shoot challenge with fellow "Drag Race" alumni Manila Luzon and Katya. She played Judy Reyes's character Quiet Ann in a season-one recap of "Claws". In 2017, she was the host of her own WoWPresents internet show, "La Vida De Valentina" which ran for seven episodes.


title: Valentina (drag queen)

text: Valentina was in the October 2017 issue of "Vogue Mexico", and filmed a makeup tutorial for "Vogue"'s YouTube channel. She was in the July 2017 issue of "Elle Mexico" modeling designs by Benito Santos for his Red Carpet 2018 campaign. She appeared in the January 2018 issue of Filipino magazine "Preview". In April 2019, Valentina appeared in "Vogue Mexico" for a second time.


title: Valentina (drag queen)

text: On November 9, 2018, Valentina was announced as a contestant on the upcoming fourth season of "RuPaul's Drag Race: All Stars," a spin-off of the regular "Drag Race" series which features returning contestants from past seasons"." After being in the bottom three times and only scoring one win, Valentina was eliminated in the seventh episode by Latrice Royale, when she failed to impress the judges in a design challenge, causing her and Naomi Smalls to be up for elimination.


title: Valentina (drag queen)

text: In January 2019, Valentina portrayed Angel Dumott Schunard in Fox's televised production of the musical "Rent", "". In June 2019, a panel of judges from "New York" magazine placed Valentina 20th on their list of "the most powerful drag queens in America", a ranking of 100 former "Drag Race" contestants. In 2021, she made a cameo appearance in "In the Heights", during "No Me Diga".


title: Valentina (drag queen)

text: "" winner Alaska Thunderfuck did a parody song of "Despacito" called "Valentina" in October 2017, with lyrics about Valentina and her infamous elimination from the show. The cosmetics company Lush also referenced Valentina’s elimination for advertising on one of their face masks.


title: Valentina (drag queen)

text: In 2019, Valentina came out as non-binary, stating that she will continue to use "she/her" pronouns. Valentina is now one of several Drag Race alumni who identify as either nonbinary or gender-nonconforming.


title: Valentina (drag queen)

text: She is one of the most followed queens from "Drag Race", and has accumulated over 1.5 million Instagram followers as of October, 2021.


title: Proteomics

text: Proteomics is the large-scale study of proteins. Proteins are vital parts of living organisms, with many functions such as the formation of structural fibers of muscle tissue, enzymatic digestion of food, or synthesis and replication of DNA. In addition, other kinds of proteins include antibodies that protect an organism from infection, and hormones that send important signals throughout the body.


title: Proteomics

text: The proteome is the entire set of proteins produced or modified by an organism or system. Proteomics enables the identification of ever-increasing numbers of proteins. This varies with time and distinct requirements, or stresses, that a cell or organism undergoes.


title: Proteomics

text: Proteomics is an interdisciplinary domain that has benefited greatly from the genetic information of various genome projects, including the Human Genome Project. It covers the exploration of proteomes from the overall level of protein composition, structure, and activity, and is an important component of functional genomics.


title: Proteomics

text: "Proteomics" generally denotes the large-scale experimental analysis of proteins and proteomes, but often refers specifically to protein purification and mass spectrometry.


title: Proteomics

text: The first studies of proteins that could be regarded as proteomics began in 1975, after the introduction of the two-dimensional gel and mapping of the proteins from the bacterium "Escherichia coli".


title: Proteomics

text: "Proteome" is blend of the words "protein" and "genome". It was coined in 1994 by then-Ph.D student Marc Wilkins at Macquarie University, which founded the first dedicated proteomics laboratory in 1995.


title: Proteomics

text: After genomics and transcriptomics, proteomics is the next step in the study of biological systems. It is more complicated than genomics because an organism's genome is more or less constant, whereas proteomes differ from cell to cell and from time to time. Distinct genes are expressed in different cell types, which means that even the basic set of proteins produced in a cell must be identified.


title: Proteomics

text: In the past this phenomenon was assessed by RNA analysis, which was found to lack correlation with protein content. It is now known that mRNA is not always translated into protein, and the amount of protein produced for a given amount of mRNA depends on the gene it is transcribed from and on the cell's physiological state. Proteomics confirms the presence of the protein and provides a direct measure of its quantity.


title: Proteomics

text: Not only does the translation from mRNA cause differences, but many proteins also are subjected to a wide variety of chemical modifications after translation. The most common and widely studied post-translational modifications include phosphorylation and glycosylation. Many of these post-translational modifications are critical to the protein's function.


title: Proteomics

text: One such modification is phosphorylation, which happens to many enzymes and structural proteins in the process of cell signaling. The addition of a phosphate to particular amino acids—most commonly serine and threonine mediated by serine-threonine kinases, or more rarely tyrosine mediated by tyrosine kinases—causes a protein to become a target for binding or interacting with a distinct set of other proteins that recognize the phosphorylated domain.


title: Proteomics

text: Because protein phosphorylation is one of the most studied protein modifications, many "proteomic" efforts are geared to determining the set of phosphorylated proteins in a particular cell or tissue-type under particular circumstances. This alerts the scientist to the signaling pathways that may be active in that instance.


title: Proteomics

text: Ubiquitin is a small protein that may be affixed to certain protein substrates by enzymes called E3 ubiquitin ligases. Determining which proteins are poly-ubiquitinated helps understand how protein pathways are regulated. This is, therefore, an additional legitimate "proteomic" study. Similarly, once a researcher determines which substrates are ubiquitinated by each ligase, determining the set of ligases expressed in a particular cell type is helpful.


title: Proteomics

text: In addition to phosphorylation and ubiquitination, proteins may be subjected to (among others) methylation, acetylation, glycosylation, oxidation, and nitrosylation. Some proteins undergo all these modifications, often in time-dependent combinations. This illustrates the potential complexity of studying protein structure and function.


title: Proteomics

text: A cell may make different sets of proteins at different times or under different conditions, for example during development, cellular differentiation, cell cycle, or carcinogenesis. Further increasing proteome complexity, as mentioned, most proteins are able to undergo a wide range of post-translational modifications.


title: Proteomics

text: Therefore, a "proteomics" study may become complex very quickly, even if the topic of study is restricted. In more ambitious settings, such as when a biomarker for a specific cancer subtype is sought, the proteomics scientist might elect to study multiple blood serum samples from multiple cancer patients to minimise confounding factors and account for experimental noise. Thus, complicated experimental designs are sometimes necessary to account for the dynamic complexity of the proteome.


title: Proteomics

text: "Reproducibility". One major factor affecting reproducibility in proteomics experiments is the simultaneous elution of many more peptides than mass spectrometers can measure. This causes stochastic differences between experiments due to data-dependent acquisition of tryptic peptides. Although early large-scale shotgun proteomics analyses showed considerable variability between laboratories, presumably due in part to technical and experimental differences between laboratories, reproducibility has been improved in more recent mass spectrometry analysis, particularly on the protein level. Notably, targeted proteomics shows increased reproducibility and repeatability compared with shotgun methods, although at the expense of data density and effectiveness.


title: Proteomics

text: "Data quality". Proteomic analysis is highly amenable to automation and large data sets are created, which are processed by software algorithms. Filter parameters are used to reduce the number of false hits, but they cannot be completely eliminated. Scientists have expressed the need for awareness that proteomics experiments should adhere to the criteria of analytical chemistry (sufficient data quality, sanity check, validation).


title: Proteomics

text: In proteomics, there are multiple methods to study proteins. Generally, proteins may be detected by using either antibodies (immunoassays), electrophoretic separation or mass spectrometry. If a complex biological sample is analyzed, either a very specific antibody needs to be used in quantitative dot blot analysis (QDB), or biochemical separation then needs to be used before the detection step, as there are too many analytes in the sample to perform accurate detection and quantification.


title: Proteomics

text: Antibodies to particular proteins, or to their modified forms, have been used in biochemistry and cell biology studies. These are among the most common tools used by molecular biologists today. There are several specific techniques and protocols that use antibodies for protein detection. The enzyme-linked immunosorbent assay (ELISA) has been used for decades to detect and quantitatively measure proteins in samples. The western blot may be used for detection and quantification of individual proteins, where in an initial step, a complex protein mixture is separated using SDS-PAGE and then the protein of interest is identified using an antibody.


title: Proteomics

text: Modified proteins may be studied by developing an antibody specific to that modification. For example, there are antibodies that only recognize certain proteins when they are tyrosine-phosphorylated, they are known as phospho-specific antibodies. Also, there are antibodies specific to other modifications. These may be used to determine the set of proteins that have undergone the modification of interest.


title: Proteomics

text: Immunoassays can also be carried out using recombinantly generated immunoglobulin derivatives or synthetically designed protein scaffolds that are selected for high antigen specificity. Such binders include single domain antibody fragments (Nanobodies), designed ankyrin repeat proteins (DARPins) and aptamers.


title: Proteomics

text: Disease detection at the molecular level is driving the emerging revolution of early diagnosis and treatment. A challenge facing the field is that protein biomarkers for early diagnosis may be present in very low abundance. The lower limit of detection with conventional immunoassay technology is the upper femtomolar range (10 M). Digital immunoassay technology has improved detection sensitivity three logs, to the attomolar range (10 M). This capability has the potential to open new advances in diagnostics and therapeutics, but such technologies have been relegated to manual procedures that are not well suited for efficient routine use.


title: Proteomics

text: While protein detection with antibodies is still very common in molecular biology, other methods have been developed as well, that do not rely on an antibody. These methods offer various advantages, for instance they often are able to determine the sequence of a protein or peptide, they may have higher throughput than antibody-based, and they sometimes can identify and quantify proteins for which no antibody exists.


title: Proteomics

text: One of the earliest methods for protein analysis has been Edman degradation (introduced in 1967) where a single peptide is subjected to multiple steps of chemical degradation to resolve its sequence. These early methods have mostly been supplanted by technologies that offer higher throughput.


title: Proteomics

text: More recently implemented methods use mass spectrometry-based techniques, a development that was made possible by the discovery of "soft ionization" methods developed in the 1980s, such as matrix-assisted laser desorption/ionization (MALDI) and electrospray ionization (ESI). These methods gave rise to the top-down and the bottom-up proteomics workflows where often additional separation is performed before analysis (see below).


title: Proteomics

text: For the analysis of complex biological samples, a reduction of sample complexity is required. This may be performed off-line by one-dimensional or two-dimensional separation. More recently, on-line methods have been developed where individual peptides (in bottom-up proteomics approaches) are separated using reversed-phase chromatography and then, directly ionized using ESI; the direct coupling of separation and analysis explains the term "on-line" analysis.


title: Proteomics

text: There are several hybrid technologies that use antibody-based purification of individual analytes and then perform mass spectrometric analysis for identification and quantification. Examples of these methods are the


title: Proteomics

text: MSIA (mass spectrometric immunoassay), developed by Randall Nelson in 1995, and the SISCAPA (Stable Isotope Standard Capture with Anti-Peptide Antibodies) method, introduced by Leigh Anderson in 2004.


title: Proteomics

text: Fluorescence two-dimensional differential gel electrophoresis (2-D DIGE) may be used to quantify variation in the 2-D DIGE process and establish statistically valid thresholds for assigning quantitative changes between samples.


title: Proteomics

text: Comparative proteomic analysis may reveal the role of proteins in complex biological systems, including reproduction. For example, treatment with the insecticide triazophos causes an increase in the content of brown planthopper ("Nilaparvata lugens" (Stål)) male accessory gland proteins (Acps) that may be transferred to females via mating, causing an increase in fecundity (i.e. birth rate) of females. To identify changes in the types of accessory gland proteins (Acps) and reproductive proteins that mated female planthoppers received from male planthoppers, researchers conducted a comparative proteomic analysis of mated "N. lugens" females. The results indicated that these proteins participate in the reproductive process of "N. lugens" adult females and males.


title: Proteomics

text: Proteome analysis of "Arabidopsis peroxisomes" has been established as the major unbiased approach for identifying new peroxisomal proteins on a large scale.


title: Proteomics

text: There are many approaches to characterizing the human proteome, which is estimated to contain between 20,000 and 25,000 non-redundant proteins. The number of unique protein species likely will increase by between 50,000 and 500,000 due to RNA splicing and proteolysis events, and when post-translational modification also are considered, the total number of unique human proteins is estimated to range in the low millions.


title: Proteomics

text: In addition, the first promising attempts to decipher the proteome of animal tumors have recently been reported.


title: Proteomics

text: Proteomics has steadily gained momentum over the past decade with the evolution of several approaches. Few of these are new, and others build on traditional methods. Mass spectrometry-based methods, affinity proteomics, and micro arrays are the most common technologies for large-scale study of proteins.


title: Proteomics

text: There are two mass spectrometry-based methods currently used for protein profiling. The more established and widespread method uses high resolution, two-dimensional electrophoresis to separate proteins from different samples in parallel, followed by selection and staining of differentially expressed proteins to be identified by mass spectrometry. Despite the advances in 2-DE and its maturity, it has its limits as well.


title: Proteomics

text: The central concern is the inability to resolve all the proteins within a sample, given their dramatic range in expression level and differing properties. The combination of pore size, and protein charge, size and shape can greatly determine migration rate which leads to other complications.


title: Proteomics

text: The second quantitative approach uses stable isotope tags to differentially label proteins from two different complex mixtures. Here, the proteins within a complex mixture are labeled isotopically first, and then digested to yield labeled peptides. The labeled mixtures are then combined, the peptides separated by multidimensional liquid chromatography and analyzed by tandem mass spectrometry. Isotope coded affinity tag (ICAT) reagents are the widely used isotope tags. In this method, the cysteine residues of proteins get covalently attached to the ICAT reagent, thereby reducing the complexity of the mixtures omitting the non-cysteine residues.


title: Proteomics

text: Quantitative proteomics using stable isotopic tagging is an increasingly useful tool in modern development. Firstly, chemical reactions have been used to introduce tags into specific sites or proteins for the purpose of probing specific protein functionalities. The isolation of phosphorylated peptides has been achieved using isotopic labeling and selective chemistries to capture the fraction of protein among the complex mixture. Secondly, the ICAT technology was used to differentiate between partially purified or purified macromolecular complexes such as large RNA polymerase II pre-initiation complex and the proteins complexed with yeast transcription factor. Thirdly, ICAT labeling was recently combined with chromatin isolation to identify and quantify chromatin-associated proteins. Finally ICAT reagents are useful for proteomic profiling of cellular organelles and specific cellular fractions.


title: Proteomics

text: Another quantitative approach is the accurate mass and time (AMT) tag approach developed by Richard D. Smith and coworkers at Pacific Northwest National Laboratory. In this approach, increased throughput and sensitivity is achieved by avoiding the need for tandem mass spectrometry, and making use of precisely determined separation time information and highly accurate mass determinations for peptide and protein identifications.


title: Proteomics

text: Affinity proteomics uses antibodies or other affinity reagents (such as oligonucleotide-based aptamers) as protein-specific detection probes. Currently this method can interrogate several thousand proteins, typically from biofluids such as plasma, serum or cerebrospinal fluid (CSF). A key differentiator for this technology is the ability to analyze hundreds or thousands of samples in a reasonable timeframe (a matter of days or weeks); mass spectrometry-based methods are not scalable to this level of sample throughput for proteomics analyses.


title: Proteomics

text: Balancing the use of mass spectrometers in proteomics and in medicine is the use of protein micro arrays. The aim behind protein micro arrays is to print thousands of protein detecting features for the interrogation of biological samples. Antibody arrays are an example in which a host of different antibodies are arrayed to detect their respective antigens from a sample of human blood. Another approach is the arraying of multiple protein types for the study of properties like protein-DNA, protein-protein and protein-ligand interactions. Ideally, the functional proteomic arrays would contain the entire complement of the proteins of a given organism. The first version of such arrays consisted of 5000 purified proteins from yeast deposited onto glass microscopic slides. Despite the success of first chip, it was a greater challenge for protein arrays to be implemented. Proteins are inherently much more difficult to work with than DNA. They have a broad dynamic range, are less stable than DNA and their structure is difficult to preserve on glass slides, though they are essential for most assays. The global ICAT technology has striking advantages over protein chip technologies.


title: Proteomics

text: This is a promising and newer microarray application for the diagnosis, study and treatment of complex diseases such as cancer. The technology merges laser capture microdissection (LCM) with micro array technology, to produce reverse-phase protein microarrays. In this type of microarrays, the whole collection of protein themselves are immobilized with the intent of capturing various stages of disease within an individual patient. When used with LCM, reverse phase arrays can monitor the fluctuating state of proteome among different cell population within a small area of human tissue. This is useful for profiling the status of cellular signaling molecules, among a cross-section of tissue that includes both normal and cancerous cells. This approach is useful in monitoring the status of key factors in normal prostate epithelium and invasive prostate cancer tissues. LCM then dissects these tissue and protein lysates were arrayed onto nitrocellulose slides, which were probed with specific antibodies. This method can track all kinds of molecular events and can compare diseased and healthy tissues within the same patient enabling the development of treatment strategies and diagnosis. The ability to acquire proteomics snapshots of neighboring cell populations, using reverse-phase microarrays in conjunction with LCM has a number of applications beyond the study of tumors. The approach can provide insights into normal physiology and pathology of all the tissues and is invaluable for characterizing developmental processes and anomalies.


title: Proteomics

text: Recent advancements in bioorthogonal chemistry have revealed applications in protein analysis. The extension of using organic molecules to observe their reaction with proteins reveals extensive methods to tag them. Unnatural amino acids and various functional groups represent new growing technologies in proteomics.


title: Proteomics

text: Specific biomolecules that are capable of being metabolized in cells or tissues are inserted into proteins or glycans. The molecule will have an affinity tag, modifying the protein allowing it to be detected. Azidohomoalanine (AHA) utilizes this affinity tag via incorporation with Met-t-RNA synthetase to incorporate into proteins. This has allowed AHA to assist in determine the identity of newly synthesized proteins created in response to perturbations and to identify proteins secreted by cells.


title: Proteomics

text: Recent studies using ketones and aldehydes condensations show that they are best suited for in vitro or cell surface labeling. However, using ketones and aldehydes as bioorthogonal reporters revealed slow kinetics indicating that while effective for labeling, the concentration must be high.


title: Proteomics

text: Certain proteins can be detected via their reactivity to azide groups. Non-proteinogenic amino acids can bear azide groups which react with phosphines in Staudinger ligations. This reaction has already been used to label other biomolecules in living cells and animals.


title: Proteomics

text: The bioorthoganal field is expanding and is driving further applications within proteomics. It is worthwhile noting the limitations and benefits. Rapid reactions can create bioconjuctions and create high concentrations with low amounts of reactants. Contrarily slow kinetic reactions like aldehyde and ketone condensation while effective require a high concentration making it cost inefficient.


title: Proteomics

text: One major development to come from the study of human genes and proteins has been the identification of potential new drugs for the treatment of disease. This relies on genome and proteome information to identify proteins associated with a disease, which computer software can then use as targets for new drugs. For example, if a certain protein is implicated in a disease, its 3D structure provides the information to design drugs to interfere with the action of the protein. A molecule that fits the active site of an enzyme, but cannot be released by the enzyme, inactivates the enzyme. This is the basis of new drug-discovery tools, which aim to find new drugs to inactivate proteins involved in disease. As genetic differences among individuals are found, researchers expect to use these techniques to develop personalized drugs that are more effective for the individual.


title: Proteomics

text: Proteomics is also used to reveal complex plant-insect interactions that help identify candidate genes involved in the defensive response of plants to herbivory.


title: Proteomics

text: A branch of proteomics called chemoproteomics provides numerous tools and techniques to detect protein targets of drugs.


title: Proteomics

text: Interaction proteomics is the analysis of protein interactions from scales of binary interactions to proteome- or network-wide. Most proteins function via protein–protein interactions, and one goal of interaction proteomics is to identify binary protein interactions, protein complexes, and interactomes.


title: Proteomics

text: Several methods are available to probe protein–protein interactions. While the most traditional method is yeast two-hybrid analysis, a powerful emerging method is affinity purification followed by protein mass spectrometry using tagged protein baits. Other methods include surface plasmon resonance (SPR), protein microarrays, dual polarisation interferometry, microscale thermophoresis, kinetic exclusion assay, and experimental methods such as phage display and "in silico" computational methods.


title: Proteomics

text: Knowledge of protein-protein interactions is especially useful in regard to biological networks and systems biology, for example in cell signaling cascades and gene regulatory networks (GRNs, where knowledge of protein-DNA interactions is also informative). Proteome-wide analysis of protein interactions, and integration of these interaction patterns into larger biological networks, is crucial towards understanding systems-level biology.


title: Proteomics

text: Expression proteomics includes the analysis of protein expression at a larger scale. It helps identify main proteins in a particular sample, and those proteins differentially expressed in related samples—such as diseased vs. healthy tissue. If a protein is found only in a diseased sample then it can be a useful drug target or diagnostic marker. Proteins with the same or similar expression profiles may also be functionally related. There are technologies such as 2D-PAGE and mass spectrometry that are used in expression proteomics.


title: Proteomics

text: The National Institutes of Health has defined a biomarker as "a characteristic that is objectively measured and evaluated as an indicator of normal biological processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention."


title: Proteomics

text: Understanding the proteome, the structure and function of each protein and the complexities of protein–protein interactions are critical for developing the most effective diagnostic techniques and disease treatments in the future. For example, proteomics is highly useful in the identification of candidate biomarkers (proteins in body fluids that are of value for diagnosis), identification of the bacterial antigens that are targeted by the immune response, and identification of possible immunohistochemistry markers of infectious or neoplastic diseases.


title: Proteomics

text: An interesting use of proteomics is using specific protein biomarkers to diagnose disease. A number of techniques allow to test for proteins produced during a particular disease, which helps to diagnose the disease quickly. Techniques include western blot, immunohistochemical staining, enzyme linked immunosorbent assay (ELISA) or mass spectrometry. Secretomics, a subfield of proteomics that studies secreted proteins and secretion pathways using proteomic approaches, has recently emerged as an important tool for the discovery of biomarkers of disease.


title: Proteomics

text: In proteogenomics, proteomic technologies such as mass spectrometry are used for improving gene annotations. Parallel analysis of the genome and the proteome facilitates discovery of post-translational modifications and proteolytic events, especially when comparing multiple species (comparative proteogenomics).


title: Proteomics

text: Structural proteomics includes the analysis of protein structures at large-scale. It compares protein structures and helps identify functions of newly discovered genes. The structural analysis also helps to understand that where drugs bind to proteins and also shows where proteins interact with each other. This understanding is achieved using different technologies such as X-ray crystallography and NMR spectroscopy.


title: Proteomics

text: Much proteomics data is collected with the help of high throughput technologies such as mass spectrometry and microarray. It would often take weeks or months to analyze the data and perform comparisons by hand. For this reason, biologists and chemists are collaborating with computer scientists and mathematicians to create programs and pipeline to computationally analyze the protein data. Using bioinformatics techniques, researchers are capable of faster analysis and data storage. A good place to find lists of current programs and databases is on the ExPASy bioinformatics resource portal. The applications of bioinformatics-based proteomics include medicine, disease diagnosis, biomarker identification, and many more.


title: Proteomics

text: Mass spectrometry and microarray produce peptide fragmentation information but do not give identification of specific proteins present in the original sample. Due to the lack of specific protein identification, past researchers were forced to decipher the peptide fragments themselves. However, there are currently programs available for protein identification. These programs take the peptide sequences output from mass spectrometry and microarray and return information about matching or similar proteins. This is done through algorithms implemented by the program which perform alignments with proteins from known databases such as UniProt and PROSITE to predict what proteins are in the sample with a degree of certainty.


title: Proteomics

text: The biomolecular structure forms the 3D configuration of the protein. Understanding the protein's structure aids in the identification of the protein's interactions and function. It used to be that the 3D structure of proteins could only be determined using X-ray crystallography and NMR spectroscopy. As of 2017, Cryo-electron microscopy is a leading technique, solving difficulties with crystallization (in X-ray crystallography) and conformational ambiguity (in NMR); resolution was 2.2Å as of 2015. Now, through bioinformatics, there are computer programs that can in some cases predict and model the structure of proteins. These programs use the chemical properties of amino acids and structural properties of known proteins to predict the 3D model of sample proteins. This also allows scientists to model protein interactions on a larger scale. In addition, biomedical engineers are developing methods to factor in the flexibility of protein structures to make comparisons and predictions.


title: Proteomics

text: Most programs available for protein analysis are not written for proteins that have undergone post-translational modifications. Some programs will accept post-translational modifications to aid in protein identification but then ignore the modification during further protein analysis. It is important to account for these modifications since they can affect the protein's structure. In turn, computational analysis of post-translational modifications has gained the attention of the scientific community. The current post-translational modification programs are only predictive. Chemists, biologists and computer scientists are working together to create and introduce new pipelines that allow for analysis of post-translational modifications that have been experimentally identified for their effect on the protein's structure and function.


title: Proteomics

text: One example of the use of bioinformatics and the use of computational methods is the study of protein biomarkers. Computational predictive models have shown that extensive and diverse feto-maternal protein trafficking occurs during pregnancy and can be readily detected non-invasively in maternal whole blood. This computational approach circumvented a major limitation, the abundance of maternal proteins interfering with the detection of fetal proteins, to fetal proteomic analysis of maternal blood. Computational models can use fetal gene transcripts previously identified in maternal whole blood to create a comprehensive proteomic network of the term neonate. Such work shows that the fetal proteins detected in pregnant woman's blood originate from a diverse group of tissues and organs from the developing fetus. The proteomic networks contain many biomarkers that are proxies for development and illustrate the potential clinical application of this technology as a way to monitor normal and abnormal fetal development.


title: Proteomics

text: An information-theoretic framework has also been introduced for biomarker discovery, integrating biofluid and tissue information. This new approach takes advantage of functional synergy between certain biofluids and tissues with the potential for clinically significant findings not possible if tissues and biofluids were considered individually. By conceptualizing tissue-biofluid as information channels, significant biofluid proxies can be identified and then used for the guided development of clinical diagnostics. Candidate biomarkers are then predicted based on information transfer criteria across the tissue-biofluid channels. Significant biofluid-tissue relationships can be used to prioritize clinical validation of biomarkers.


title: Proteomics

text: A number of emerging concepts have the potential to improve the current features of proteomics. Obtaining absolute quantification of proteins and monitoring post-translational modifications are the two tasks that impact the understanding of protein function in healthy and diseased cells. For many cellular events, the protein concentrations do not change; rather, their function is modulated by post-translational modifications (PTM). Methods of monitoring PTM are an underdeveloped area in proteomics. Selecting a particular subset of protein for analysis substantially reduces protein complexity, making it advantageous for diagnostic purposes where blood is the starting material. Another important aspect of proteomics, yet not addressed, is that proteomics methods should focus on studying proteins in the context of the environment. The increasing use of chemical cross-linkers, introduced into living cells to fix protein-protein, protein-DNA and other interactions, may ameliorate this problem partially. The challenge is to identify suitable methods of preserving relevant interactions. Another goal for studying protein is to develop more sophisticated methods to image proteins and other molecules in living cells and real-time.


title: Proteomics

text: Advances in quantitative proteomics would clearly enable more in-depth analysis of cellular systems. Another research frontier is the analysis of single cells, and protein covariation across single cells which reflects biological processes such as protein complex formation, immune functions, as well as cell cycle and priming of cancer cells for drug resistance Biological systems are subject to a variety of perturbations (cell cycle, cellular differentiation, carcinogenesis, environment (biophysical), etc.). Transcriptional and translational responses to these perturbations results in functional changes to the proteome implicated in response to the stimulus. Therefore, describing and quantifying proteome-wide changes in protein abundance is crucial towards understanding biological phenomenon more holistically, on the level of the entire system. In this way, proteomics can be seen as complementary to genomics, transcriptomics, epigenomics, metabolomics, and other -omics approaches in integrative analyses attempting to define biological phenotypes more comprehensively. As an example, "The Cancer Proteome Atlas" provides quantitative protein expression data for ~200 proteins in over 4,000 tumor samples with matched transcriptomic and genomic data from The Cancer Genome Atlas. Similar datasets in other cell types, tissue types, and species, particularly using deep shotgun mass spectrometry, will be an immensely important resource for research in fields like cancer biology, developmental and stem cell biology, medicine, and evolutionary biology.


title: Proteomics

text: Characterizing the human plasma proteome has become a major goal in the proteomics arena, but it is also the most challenging proteomes of all human tissues. It contains immunoglobulin, cytokines, protein hormones, and secreted proteins indicative of infection on top of resident, hemostatic proteins. It also contains tissue leakage proteins due to the blood circulation through different tissues in the body. The blood thus contains information on the physiological state of all tissues and, combined with its accessibility, makes the blood proteome invaluable for medical purposes. It is thought that characterizing the proteome of blood plasma is a daunting challenge.


title: Proteomics

text: The depth of the plasma proteome encompasses a dynamic range of more than 10 between the highest abundant protein (albumin) and the lowest (some cytokines) and is thought to be one of the main challenges for proteomics. Temporal and spatial dynamics further complicate the study of human plasma proteome. The turnover of some proteins is quite faster than others and the protein content of an artery may substantially vary from that of a vein. All these differences make even the simplest proteomic task of cataloging the proteome seem out of reach. To tackle this problem, priorities need to be established. Capturing the most meaningful subset of proteins among the entire proteome to generate a diagnostic tool is one such priority. Secondly, since cancer is associated with enhanced glycosylation of proteins, methods that focus on this part of proteins will also be useful. Again: multiparameter analysis best reveals a pathological state. As these technologies improve, the disease profiles should be continually related to respective gene expression changes. Due to the above-mentioned problems plasma proteomics remained challenging. However, technological advancements and continuous developments seem to result in a revival of plasma proteomics as it was shown recently by a technology called plasma proteome profiling. Due to such technologies researchers were able to investigate inflammation processes in mice, the heritability of plasma proteomes as well as to show the effect of such a common life style change like weight loss on the plasma proteome.


title: Proteomics

text: Numerous journals are dedicated to the field of proteomics and related areas. Note that journals dealing with "proteins" are usually more focused on structure and function while "proteomics" journals are more focused on the large-scale analysis of whole proteomes or at least large sets of proteins. Some of the more important ones are listed below (with their publishers).


title: Aberdeen Proving Ground

text: Aberdeen Proving Ground (APG) (sometimes erroneously called Aberdeen Proving "Grounds") is a U.S. Army facility located adjacent to Aberdeen, Harford County, Maryland, United States. More than 7,500 civilians and 5,000 military personnel work at APG.There are 11 major commands among the tenant units, including:


title: Aberdeen Proving Ground

text: APG is the U.S. Army's oldest active proving ground, established on 20 October 1917, six months after the U.S. entered World War I. The planning and construction were overseen by Brigadier General Colden Ruggles, who later served as the Army's Chief of Ordnance. Its location allowed design and testing of ordnance materiel to take place near contemporary industrial and shipping centers. The proving ground was created as a successor to the Sandy Hook Proving Ground, which was too small for some of the larger weapons being tested. At the peak of World War II, APG had billeting space for 2,348 officers and 24,189 enlisted personnel.


title: Aberdeen Proving Ground

text: Aberdeen was home to the Army Pulse Radiation Facility Reactor, in 1968. On 6 September 1968, this reactor was the site of a prompt critical excursion during commissioning tests. This accident harmed no personnel but did release enough heat to reach the melting point of the fuel in the core, 1150°C. This caused damage to the fuel components of the reactor, fusing the four central rings together. This is one of thirty-three prompt critical accidents worldwide, between 1949 and 2000.


title: Aberdeen Proving Ground

text: Under the Base Realignment and Closure (BRAC) program, as announced in 2005, the APG is projected to lose the Ordnance School and associated R&D facilities with 3862 military and 290 civilian jobs moving to Fort Lee, Virginia. APG will gain 451 military and 5,661 civilian jobs from Fort Monmouth, New Jersey. There is a net loss of 3,411 military jobs under BRAC and a net gain of 5,371 civilian jobs.


title: Aberdeen Proving Ground

text: Although civilian contractors produced the major portion of conventional munitions for World War I, the United States government built federally owned plants on Aberdeen Proving Ground for the manufacture of toxic gas. These poison gas manufacturing facilities came to be known as Edgewood Arsenal. Edgewood Arsenal included plants to manufacture mustard gas, chloropicrin and phosgene, and separate facilities to fill artillery shells with these chemicals. Production began in 1918, reached per month, and totaled of toxic gas manufactured at Edgewood Arsenal before the November 1918 armistice. Some of this gas was shipped overseas for use in French and British artillery shells.


title: Aberdeen Proving Ground

text: The Edgewood area of Aberdeen Proving Ground is approximately or . The Edgewood area was used for the development and testing of chemical agent munitions. From 1917 to the present, the Edgewood area conducted chemical research programs, manufactured chemical agents, and tested, stored, and disposed of toxic materials.


title: Aberdeen Proving Ground

text: From 1955 to 1975, the U.S. Army Chemical Corps conducted classified medical studies at Edgewood Arsenal, Maryland. The purpose was to evaluate the impact of low-dose chemical warfare agents on military personnel and to test protective clothing and pharmaceuticals. About 7,000 soldiers took part in these experiments that involved exposures to more than 250 different chemicals, according to the Department of Defense (DoD). Some of the volunteers exhibited symptoms at the time of exposure to these agents but long-term follow-up was not planned as part of the DoD studies.


title: Aberdeen Proving Ground

text: During the week of July 14, 1969, personnel from Naval Applied Science Laboratory in conjunction with personnel from Limited War Laboratory conducted a defoliation test along the shoreline of Poole's Island, Aberdeen Proving Ground using Agent Orange and Agent Orange Plus foam.


title: Aberdeen Proving Ground

text: The Gunpowder Meetinghouse and Presbury Meetinghouse located within the grounds of Edgewood Arsenal are listed on the National Register of Historic Places.