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Palo Alto, California
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Palo Alto is a charter city located in the northwest corner of Santa Clara County, California, in the San Francisco Bay Area of the United States. The city shares its borders with East Palo Alto, Mountain View, Los Altos, Los Altos Hills, Stanford, Portola Valley and it is named after a coast redwood tree called El Palo Alto. Palo Alto was established by Leland Stanford Sr. when he founded Stanford University, following the death of his son and it has also served as an incubator to several other high-technology companies such as Google, Facebook, Logitech, Intuit, Pinterest, and PayPal. As of the 2010 census, the total resident population is 64,403. Palo Alto is one of the most expensive cities in the United States, the recorded history of Palo Alto dates back to 1769, when Gaspar de Portolá noted an Ohlone settlement. This remains an area of known Indian mounds, a plaque at Middlefield Road and Embarcadero Road commemorates the area. The city got its name from a tall coast redwood tree, named El Palo Alto, a plaque there recounts the story of the Portolà expedition, a 63-man, 200-horse expedition from San Diego to Monterey from November 7–11,1769. The group overshot Monterey in the fog and when they reached modern-day Pacifica, they ascended Sweeney Ridge, thinking the bay was too wide to cross, the group retraced their journey to Monterey, never becoming aware of the Golden Gate entrance to the Bay. Located south of the San Francisquito Creek, west of todays I-280, in 1835, Rafael Soto and family settled near the San Francisquito Creek near Newell and Middlefield, selling goods to travelers. Rafael Soto died in 1839, but his wife, Maria Antonia Mesa, was granted Rancho Rinconada del Arroyo de San Francisquito in 1841, in 1839, their daughter María Luisa Soto married John Coppinger, who was the grantee of Rancho Cañada de Raymundo. Rancho Cañada de Raymundo was West of San Francisquito Creek, and began at Alambique Creek, the border of Rancho Corte de Madera. Bear Gulch Creek flowed on his land in Portola Valley, the rancho also abutted Buelnas grant near Skyline Boulevard and Matadero Creek. Upon Coppingers death, Maria inherited it and later married a visiting boat captain, Greer owned a home on the site that is now Town & Country Village on Embarcadero and El Camino Real. Greer Avenue and Court are named for him, to the west of Rafael Soto, near El Camino and following the Creek, was Rancho San Francisquito granted in 1839 to Antonio Buelna and wife Maria Concepcion. To the south of the Sotos, the brothers Secundino and Teodoro Robles in 1849 bought Rancho Rincon de San Francisquito from José Peña, where the Joness house was, then east down Arastradero Rd. to the north property line of Alta Mesa Memorial Park and Terman Park. The property then went along the bay to the Embarcadero, a boundary in the day, then up to the Stanford University gates, up Galvez. The grant was bounded on the south by Mariano Castros Rancho Pastoria de las Borregas grant across San Antonio Road, thats the Robles Rancho, about 80% of Palo Alto and Stanford University. It was whittled down by 1863 through courts to 6,981 acres, stories say their grand hacienda was built on the former meager adobe of José Peña near Ferne off San Antonio Road, midway between Middlefield and Alma Street
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Food and Drug Administration
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The Food and Drug Administration is a federal agency of the United States Department of Health and Human Services, one of the United States federal executive departments. As of 2017, 3/4th of the FDA budget is funded by the pharmaceutical companies due to the Prescription drug user fee act and these include regulating lasers, cellular phones, condoms and control of disease on products ranging from certain household pets to sperm donation for assisted reproduction. The FDA is led by the Commissioner of Food and Drugs, appointed by the President with the advice, the Commissioner reports to the Secretary of Health and Human Services. Dr. Robert M. Califf, MD is the current commissioner, who took over in February 2016 for Dr. Stephen Ostroff, the FDA has its headquarters in unincorporated White Oak, Maryland. The agency also has 223 field offices and 13 laboratories located throughout the 50 states, the United States Virgin Islands, in 2008, the FDA began to post employees to foreign countries, including China, India, Costa Rica, Chile, Belgium, and the United Kingdom. The site was renamed from the White Oak Naval Surface Warfare Center to the Federal Research Center at White Oak, the first building, the Life Sciences Laboratory, was dedicated and opened with 104 employees on the campus in December 2003. Only one original building from the facility was kept. All other buildings are new construction, the project is slated to be completed by 2017, assuming future Congressional funding While most of the Centers are located in the Washington, D. C. The Office of Regulatory Affairs is considered the eyes and ears of the agency, the Office of Regulatory Affairs is divided into five regions, which are further divided into 20 districts. Districts are based roughly on the divisions of the federal court system. Each district comprises a main office and a number of Resident Posts. ORA also includes the Agencys network of laboratories, which analyze any physical samples taken. Though samples are usually food-related, some laboratories are equipped to analyze drugs, cosmetics, the Office of Criminal Investigations was established in 1991 to investigate criminal cases. Unlike ORA Investigators, OCI Special Agents are armed, and dont focus on aspects of the regulated industries. In many cases, OCI pursues cases involving Title 18 violations, OCI Special Agents often come from other criminal investigations backgrounds, and work closely with the Federal Bureau of Investigation, Assistant Attorney General, and even Interpol. OCI receives cases from a variety of sources—including ORA, local agencies, OCI is a smaller branch, comprising about 200 agents nationwide. The FDA frequently works with federal agencies, including the Department of Agriculture, Drug Enforcement Administration, Customs and Border Protection. Often local and state government agencies also work with the FDA to provide regulatory inspections, the FDA regulates more than US$1 trillion worth of consumer goods, about 25% of consumer expenditures in the United States
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Clinical trial
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Clinical trials are experiments or observations done in clinical research. Clinical trials generate data on safety and efficacy and they are conducted only after they have received health authority/ethics committee approval in the country where approval of the therapy is sought. These authorities are responsible for vetting the risk/benefit ratio of the trial – their approval does not mean that the therapy is safe or effective, only that the trial may be conducted. Clinical trials can vary in size and cost, and they can involve a research center or multiple centers. Clinical study design aims to ensure the validity and reproducibility of the results. Trials can be costly, depending on a number of factors. The sponsor may be an organization or a pharmaceutical, biotechnology or medical device company. Certain functions necessary to the trial, such as monitoring and lab work, may be managed by an outsourced partner, only 10 percent of all drugs started in human clinical trials become an approved drug. Some clinical trials involve healthy subjects with no pre-existing medical conditions, other clinical trials pertain to patients with specific health conditions who are willing to try an experimental treatment. When participants are healthy volunteers who receive financial incentives, the goals are different than when the participants are sick, during dosing periods, study subjects typically remain under supervision for one to 40 nights. Usually pilot experiments are conducted to gain insights for design of the trial to follow. There are two goals to testing medical treatments, to whether they work well enough, called efficacy or effectiveness. The benefits must outweigh the risks, in the US, the elderly constitute only 14 percent of the population, while they consume over one-third of drugs. Women, children and people with unrelated medical conditions are frequently excluded. For women, a reason for exclusion is the possibility of pregnancy. If the sponsor cannot obtain enough test subjects at one location investigators at other locations are recruited to join the study, during the trial, investigators recruit subjects with the predetermined characteristics, administer the treatment and collect data on the subjects health for a defined time period. The researchers send the data to the sponsor, who then analyzes the pooled data using statistical tests. Except for small, single-location trials, the design and objectives are specified in a document called a clinical trial protocol
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National Institutes of Health
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The National Institutes of Health is a biomedical research facility primarily located in Bethesda, Maryland. An agency of the United States Department of Health and Human Services, it is the agency of the United States government responsible for biomedical. The NIH comprises 27 separate institutes and centers that conduct research in different disciplines of biomedical science, NIHs roots extend back to a Marine Hospital Service in the late 1790s that provided medical relief to sick and disabled men in the U. S. Navy. By 1870, a network of hospitals had developed and was placed under the charge of a medical officer within the Bureau of the Treasury Department. In 1887 a laboratory for the study of bacteria, the Hygienic Laboratory, was established at the Marine Hospital in New York, in the early 1900s, Congress began appropriating funds for the Marine Hospital Service. By 1922, this changed its name to Public Health Services. This marked the beginning of a partnership with universities, in 1930, the Hygienic Laboratory was re-designated as the National Institute of Health by the Ransdell Act and was given $750,000 to construct two NIH buildings. Over the next few decades, Congress would increase its funding tremendously to the NIH, in 1944, the Public Health Service Act was approved, and National Cancer Institute became a division of NIH. In 1948, the changed from National Institute of Health to National Institutes of Health. In the 1960s prominent virologist and cancer researcher Chester M. Southam injected HeLa cancer cells into patients at the Jewish Chronic Disease Hospital, when three doctors resigned after refusing to inject patients without their consent, this experiment gained considerable media attention. The NIH was a source of funding for Southam’s research and had required all research involving human subjects to obtain their consent prior to any experimentation. }Upon investigating all of their grantee institutions. From then on, the NIH has required all grantee institutions to approve any research involving human experimentation with review boards. In 1967 the Division of Regional Medical Programs was created to administer grants for research for heart disease, cancer, and strokes. That same year, the NIH director lobbied the White House for increased funding in order to increase research. An advisory committee was formed to further development of the NIH. The funding of NIH has often been a source of contention in Congress and this contention was seen most dramatically during the 1980s, when President Reagan repeatedly tried to cut funding for research, only to see Congress partly restore funding. But it was not until July 1987, as NIH celebrated its 100th anniversary, by the 1990s, the focus of the NIH committee had shifted to DNA research, and the Human Genome Project was launched. In 2009, President Obama reinstated federally funded research, revoking the ban imposed by President Bush in 2001
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University of Washington
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The University of Washington, commonly referred to as simply Washington, UW, or informally U-Dub, is a public flagship research university in Seattle, Washington, United States. Founded in 1861, Washington is one of the oldest universities on the West Coast, the university has three campuses, the oldest and largest in the University District of Seattle and two others in Tacoma and Bothell. Washington is a member of the Association of American Universities and is ranked among the top 15 universities in the world by a variety of international publications. In athletics, the university competes in the NCAA Division I Pac-12 Conference and its athletic teams are called the Huskies. Seattle was one of several settlements in the mid to late 19th century vying for primacy in the new Washington Territory, in 1854, territorial governor Isaac Stevens recommended the establishment of a university in Washington. Several prominent Seattle-area residents, chief among them Methodist preacher Daniel Bagley and they convinced early founder of Seattle and member of the territorial legislature Arthur A. Denny of the importance of Seattle winning the school. When no site emerged, the legislature, encouraged by Denny, in 1861, scouting began for an appropriate 10 acres site in Seattle to serve as the campus for a new university. Arthur and Mary Denny donated eight acres, and fellow pioneers Edward Lander and Charlie and this tract was bounded by 4th and 6th Avenues on the west and east and Union and Seneca Streets on the north and south. UW opened on November 4,1861, as the Territorial University of Washington, the following year, the legislature passed articles incorporating the University and establishing a Board of Regents. The school struggled initially, closing three times, in 1863 for lack of students, and again in 1867 and 1876 due to shortage of funds. However, Clara Antoinette McCarty Wilt became the first graduate of UW in 1876 when she graduated from UW with a degree in science. By the time Washington entered the Union in 1889, both Seattle and the University had grown substantially, enrollment increased from 30 students to nearly 300, and the relative isolation of the campus had given way to encroaching development. A special legislative committee headed by UW graduate Edmond Meany was created to find a new campus able to serve the growing student population. The committee selected a site on Union Bay northeast of downtown, the university relocated from downtown to the new campus in 1895, moving into the newly built Denny Hall. The regents tried and failed to sell the old campus, the University still owns what is now called the Metropolitan Tract. In the heart of the city, it is among the most valuable pieces of estate in Seattle. The original Territorial University building was torn down in 1908 and its former site houses the Fairmont Olympic Hotel. The sole surviving remnants of UWs first building are four 24-foot, white, hand-fluted cedar and they were salvaged by Edmond S. Meany—one of the Universitys first graduates and the former head of the history department
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Protein
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Proteins are large biomolecules, or macromolecules, consisting of one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, responding to stimuli, a linear chain of amino acid residues is called a polypeptide. A protein contains at least one long polypeptide, short polypeptides, containing less than 20–30 residues, are rarely considered to be proteins and are commonly called peptides, or sometimes oligopeptides. The individual amino acid residues are bonded together by peptide bonds, the sequence of amino acid residues in a protein is defined by the sequence of a gene, which is encoded in the genetic code. In general, the code specifies 20 standard amino acids, however. Sometimes proteins have non-peptide groups attached, which can be called prosthetic groups or cofactors, proteins can also work together to achieve a particular function, and they often associate to form stable protein complexes. Once formed, proteins only exist for a period of time and are then degraded and recycled by the cells machinery through the process of protein turnover. A proteins lifespan is measured in terms of its half-life and covers a wide range and they can exist for minutes or years with an average lifespan of 1–2 days in mammalian cells. Abnormal and or misfolded proteins are degraded more rapidly due to being targeted for destruction or due to being unstable. Like other biological macromolecules such as polysaccharides and nucleic acids, proteins are essential parts of organisms, many proteins are enzymes that catalyse biochemical reactions and are vital to metabolism. Proteins also have structural or mechanical functions, such as actin and myosin in muscle and the proteins in the cytoskeleton, other proteins are important in cell signaling, immune responses, cell adhesion, and the cell cycle. In animals, proteins are needed in the diet to provide the essential amino acids that cannot be synthesized, digestion breaks the proteins down for use in the metabolism. Methods commonly used to study structure and function include immunohistochemistry, site-directed mutagenesis, X-ray crystallography, nuclear magnetic resonance. Most proteins consist of linear polymers built from series of up to 20 different L-α-amino acids, all proteinogenic amino acids possess common structural features, including an α-carbon to which an amino group, a carboxyl group, and a variable side chain are bonded. Only proline differs from this structure as it contains an unusual ring to the N-end amine group. The amino acids in a chain are linked by peptide bonds. Once linked in the chain, an individual amino acid is called a residue, and the linked series of carbon, nitrogen. The peptide bond has two forms that contribute some double-bond character and inhibit rotation around its axis, so that the alpha carbons are roughly coplanar
7.
Dominance (genetics)
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Dominance in genetics is a relationship between alleles of one gene, in which the effect on phenotype of one allele masks the contribution of a second allele at the same locus. The first allele is dominant and the allele is recessive. For genes on an autosome, the alleles and their traits are autosomal dominant or autosomal recessive. Dominance is a key concept in Mendelian inheritance and classical genetics, often the dominant allele codes for a functional protein whereas the recessive allele does not. A classic example of dominance is the inheritance of seed shape in peas, peas may be round, associated with allele R or wrinkled, associated with allele r. In this case, three combinations of alleles are possible, RR, Rr, and rr, the RR individuals have round peas and the rr individuals have wrinkled peas. In Rr individuals the R allele masks the presence of the r allele, thus, allele R is dominant to allele r, and allele r is recessive to allele R. This use of upper case letters for dominant alleles and lower case ones for recessive alleles is a widely followed convention, more generally, where a gene exists in two allelic versions, three combinations of alleles are possible, AA, Aa, and aa. Dominance is not inherent to either an allele or its phenotype and it is a relationship between two alleles of a gene and their associated phenotypes, one allele can be dominant over a second allele, recessive to a third allele, and codominant to a fourth. Also, an allele may be dominant for an aspect of phenotype. Dominance differs from epistasis, a relationship in which an allele of one gene affects the expression of another allele at a different gene, the concept of dominance was introduced by Gregor Johann Mendel. Though Mendel, The Father of Genetics, first used the term in the 1860s, when bred separately, the plants always produced the same phenotypes, generation after generation. However, when lines with different phenotypes were crossed, one, Mendel did not use the terms gene, allele, phenotype, genotype, homozygote, and heterozygote, all of which were introduced later. He did introduce the notation of capital and lowercase letters for dominant and recessive alleles, respectively, most animals and some plants have paired chromosomes, and are described as diploid. They have two versions of each chromosome, one contributed by the mothers ovum, and the other by the sperm, known as gametes, described as haploid. Each chromosome of a pair is structurally similar to the other. The DNA in each chromosome functions as a series of genes that influence various traits. Thus, each also has a corresponding homologue, which may exist in different versions called alleles
8.
Axon
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An axon, is a long, slender projection of a nerve cell, or neuron, that typically conducts electrical impulses away from the neurons cell body. Axons are also known as nerve fibers, the function of the axon is to transmit information to different neurons, muscles and glands. Axon dysfunction has caused many inherited and acquired neurological disorders which can affect both the peripheral and central neurons, nerve fibers are classed into three types – A delta fibers, B fibers, and C fibres. A and B are myelinated and C are unmyelinated, an axon is one of two types of protoplasmic protrusions that extrude from the cell body of a neuron, the other type being dendrites. Axons are distinguished from dendrites by several features, including shape, length, all of these rules have exceptions, however. Axons are covered by a known as axolemma, the cytoplasm of axon is called axoplasm. Some types of neurons have no axon and transmit signals from their dendrites, no neuron ever has more than one axon, however in invertebrates such as insects or leeches the axon sometimes consists of several regions that function more or less independently of each other. Most axons branch, in cases very profusely. Axons make contact with other cells—usually other neurons but sometimes muscle or gland cells—at junctions called synapses, at a synapse, the membrane of the axon closely adjoins the membrane of the target cell, and special molecular structures serve to transmit electrical or electrochemical signals across the gap. Some synaptic junctions appear partway along an axon as it extends—these are called en passant synapses, other synapses appear as terminals at the ends of axonal branches. A single axon, with all its branches together, can innervate multiple parts of the brain. Axons are the transmission lines of the nervous system. Some axons can extend up to one meter or more while others extend as little as one millimeter, the longest axons in the human body are those of the sciatic nerve, which run from the base of the spinal cord to the big toe of each foot. The diameter of axons is also variable, most individual axons are microscopic in diameter. The largest mammalian axons can reach a diameter of up to 20 µm, the squid giant axon, which is specialized to conduct signals very rapidly, is close to 1 millimetre in diameter, the size of a small pencil lead. Axonal arborization also differs from one nerve fiber to the next, axons in the central nervous system typically show complex trees with many branch points. In comparison, the granule cell axon is characterized by a single T-shaped branch node from which two parallel fibers extend. Elaborate arborization allows for the transmission of messages to a large number of target neurons within a single region of the brain
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Gene
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A gene is a locus of DNA which is made up of nucleotides and is the molecular unit of heredity. The transmission of genes to an offspring is the basis of the inheritance of phenotypic traits. These genes make up different DNA sequences called genotypes, genotypes along with environmental and developmental factors determine what the phenotypes will be. Most biological traits are under the influence of polygenes as well as gene–environment interactions, genes can acquire mutations in their sequence, leading to different variants, known as alleles, in the population. These alleles encode slightly different versions of a protein, which cause different phenotypical traits, usage of the term having a gene typically refers to containing a different allele of the same, shared gene. Genes evolve due to natural selection or survival of the fittest of the alleles, the concept of a gene continues to be refined as new phenomena are discovered. For example, regulatory regions of a gene can be far removed from its coding regions, some viruses store their genome in RNA instead of DNA and some gene products are functional non-coding RNAs. The existence of discrete inheritable units was first suggested by Gregor Mendel, from 1857 to 1864, in Brno, he studied inheritance patterns in 8000 common edible pea plants, tracking distinct traits from parent to offspring. He described these mathematically as 2n combinations where n is the number of differing characteristics in the original peas, although he did not use the term gene, he explained his results in terms of discrete inherited units that give rise to observable physical characteristics. This description prefigured the distinction between genotype and phenotype, charles Darwin developed a theory of inheritance he termed pangenesis, from Greek pan and genesis / genos. Darwin used the term gemmule to describe hypothetical particles that would mix during reproduction, de Vries called these units pangenes, after Darwins 1868 pangenesis theory. In 1909 the Danish botanist Wilhelm Johannsen shortened the name to gene, advances in understanding genes and inheritance continued throughout the 20th century. Deoxyribonucleic acid was shown to be the repository of genetic information by experiments in the 1940s to 1950s. In the early 1950s the prevailing view was that the genes in a chromosome acted like discrete entities, indivisible by recombination, collectively, this body of research established the central dogma of molecular biology, which states that proteins are translated from RNA, which is transcribed from DNA. This dogma has since shown to have exceptions, such as reverse transcription in retroviruses. The modern study of genetics at the level of DNA is known as molecular genetics, in 1972, Walter Fiers and his team at the University of Ghent were the first to determine the sequence of a gene, the gene for Bacteriophage MS2 coat protein. The subsequent development of chain-termination DNA sequencing in 1977 by Frederick Sanger improved the efficiency of sequencing, an automated version of the Sanger method was used in early phases of the Human Genome Project. The theories developed in the 1930s and 1940s to integrate molecular genetics with Darwinian evolution are called the evolutionary synthesis
. PMID 14661163.
