The Jmol applet, among other abilities, offers an alternative to the Chime plug-in, no longer under active development. While Jmol has many features that Chime lacks, it does not claim to reproduce all Chime functions, most notably, the Sculpt mode. Chime requires plug-in installation and Internet Explorer 6.0 or Firefox 2.0 on Microsoft Windows, or Netscape Communicator 4.8 on Mac OS 9. Jmol operates on a wide variety of platforms. For example, Jmol is functional in Mozilla Firefox, Internet Explorer, Google Chrome, Safari. Chemistry Development Kit Comparison of software for molecular mechanics modeling Jmol extension for MediaWiki List of molecular graphics systems Molecular graphics Molecule editor Proteopedia PyMOL SAMSON Official website Wiki with listings of websites and moodles Willighagen, Egon. "Fast and Scriptable Molecular Graphics in Web Browsers without Java3D". Doi:10.1038/npre.2007.50.1
European Chemicals Agency
The European Chemicals Agency is an agency of the European Union which manages the technical and administrative aspects of the implementation of the European Union regulation called Registration, Evaluation and Restriction of Chemicals. ECHA is the driving force among regulatory authorities in implementing the EU's chemicals legislation. ECHA helps companies to comply with the legislation, advances the safe use of chemicals, provides information on chemicals and addresses chemicals of concern, it is located in Finland. The agency headed by Executive Director Bjorn Hansen, started working on 1 June 2007; the REACH Regulation requires companies to provide information on the hazards and safe use of chemical substances that they manufacture or import. Companies register this information with ECHA and it is freely available on their website. So far, thousands of the most hazardous and the most used substances have been registered; the information is technical but gives detail on the impact of each chemical on people and the environment.
This gives European consumers the right to ask retailers whether the goods they buy contain dangerous substances. The Classification and Packaging Regulation introduces a globally harmonised system for classifying and labelling chemicals into the EU; this worldwide system makes it easier for workers and consumers to know the effects of chemicals and how to use products safely because the labels on products are now the same throughout the world. Companies need to notify ECHA of the labelling of their chemicals. So far, ECHA has received over 5 million notifications for more than 100 000 substances; the information is available on their website. Consumers can check chemicals in the products. Biocidal products include, for example, insect disinfectants used in hospitals; the Biocidal Products Regulation ensures that there is enough information about these products so that consumers can use them safely. ECHA is responsible for implementing the regulation; the law on Prior Informed Consent sets guidelines for the import of hazardous chemicals.
Through this mechanism, countries due to receive hazardous chemicals are informed in advance and have the possibility of rejecting their import. Substances that may have serious effects on human health and the environment are identified as Substances of Very High Concern 1; these are substances which cause cancer, mutation or are toxic to reproduction as well as substances which persist in the body or the environment and do not break down. Other substances considered. Companies manufacturing or importing articles containing these substances in a concentration above 0,1% weight of the article, have legal obligations, they are required to inform users about the presence of the substance and therefore how to use it safely. Consumers have the right to ask the retailer whether these substances are present in the products they buy. Once a substance has been identified in the EU as being of high concern, it will be added to a list; this list is available on ECHA's website and shows consumers and industry which chemicals are identified as SVHCs.
Substances placed on the Candidate List can move to another list. This means that, after a given date, companies will not be allowed to place the substance on the market or to use it, unless they have been given prior authorisation to do so by ECHA. One of the main aims of this listing process is to phase out SVHCs where possible. In its 2018 substance evaluation progress report, ECHA said chemical companies failed to provide “important safety information” in nearly three quarters of cases checked that year. "The numbers show a similar picture to previous years" the report said. The agency noted that member states need to develop risk management measures to control unsafe commercial use of chemicals in 71% of the substances checked. Executive Director Bjorn Hansen called non-compliance with REACH a "worry". Industry group CEFIC acknowledged the problem; the European Environmental Bureau called for faster enforcement to minimise chemical exposure. European Chemicals Bureau Official website
Simplified molecular-input line-entry system
The simplified molecular-input line-entry system is a specification in the form of a line notation for describing the structure of chemical species using short ASCII strings. SMILES strings can be imported by most molecule editors for conversion back into two-dimensional drawings or three-dimensional models of the molecules; the original SMILES specification was initiated in the 1980s. It has since been extended. In 2007, an open standard called. Other linear notations include the Wiswesser line notation, ROSDAL, SYBYL Line Notation; the original SMILES specification was initiated by David Weininger at the USEPA Mid-Continent Ecology Division Laboratory in Duluth in the 1980s. Acknowledged for their parts in the early development were "Gilman Veith and Rose Russo and Albert Leo and Corwin Hansch for supporting the work, Arthur Weininger and Jeremy Scofield for assistance in programming the system." The Environmental Protection Agency funded the initial project to develop SMILES. It has since been modified and extended by others, most notably by Daylight Chemical Information Systems.
In 2007, an open standard called "OpenSMILES" was developed by the Blue Obelisk open-source chemistry community. Other'linear' notations include the Wiswesser Line Notation, ROSDAL and SLN. In July 2006, the IUPAC introduced the InChI as a standard for formula representation. SMILES is considered to have the advantage of being more human-readable than InChI; the term SMILES refers to a line notation for encoding molecular structures and specific instances should be called SMILES strings. However, the term SMILES is commonly used to refer to both a single SMILES string and a number of SMILES strings; the terms "canonical" and "isomeric" can lead to some confusion when applied to SMILES. The terms are not mutually exclusive. A number of valid SMILES strings can be written for a molecule. For example, CCO, OCC and CC all specify the structure of ethanol. Algorithms have been developed to generate the same SMILES string for a given molecule; this SMILES is unique for each structure, although dependent on the canonicalization algorithm used to generate it, is termed the canonical SMILES.
These algorithms first convert the SMILES to an internal representation of the molecular structure. Various algorithms for generating canonical SMILES have been developed and include those by Daylight Chemical Information Systems, OpenEye Scientific Software, MEDIT, Chemical Computing Group, MolSoft LLC, the Chemistry Development Kit. A common application of canonical SMILES is indexing and ensuring uniqueness of molecules in a database; the original paper that described the CANGEN algorithm claimed to generate unique SMILES strings for graphs representing molecules, but the algorithm fails for a number of simple cases and cannot be considered a correct method for representing a graph canonically. There is no systematic comparison across commercial software to test if such flaws exist in those packages. SMILES notation allows the specification of configuration at tetrahedral centers, double bond geometry; these are structural features that cannot be specified by connectivity alone and SMILES which encode this information are termed isomeric SMILES.
A notable feature of these rules is. The term isomeric SMILES is applied to SMILES in which isotopes are specified. In terms of a graph-based computational procedure, SMILES is a string obtained by printing the symbol nodes encountered in a depth-first tree traversal of a chemical graph; the chemical graph is first trimmed to remove hydrogen atoms and cycles are broken to turn it into a spanning tree. Where cycles have been broken, numeric suffix labels are included to indicate the connected nodes. Parentheses are used to indicate points of branching on the tree; the resultant SMILES form depends on the choices: of the bonds chosen to break cycles, of the starting atom used for the depth-first traversal, of the order in which branches are listed when encountered. Atoms are represented by the standard abbreviation of the chemical elements, in square brackets, such as for gold. Brackets may be omitted in the common case of atoms which: are in the "organic subset" of B, C, N, O, P, S, F, Cl, Br, or I, have no formal charge, have the number of hydrogens attached implied by the SMILES valence model, are the normal isotopes, are not chiral centers.
All other elements must be enclosed in brackets, have charges and hydrogens shown explicitly. For instance, the SMILES for water may be written as either O or. Hydrogen may be written as a separate atom; when brackets are used, the symbol H is added if the atom in brackets is bonded to one or more hydrogen, followed by the number of hydrogen atoms if greater than 1 by the sign + for a positive charge or by - for a negative charge. For example, for ammonium. If there is more than one charge, it is written as digit.
Estrogen receptors are a group of proteins found inside cells. They are receptors. Two classes of ER exist: nuclear estrogen receptors, which are members of the nuclear receptor family of intracellular receptors, membrane estrogen receptors, which are G protein-coupled receptors; this article refers to the former. Once activated by estrogen, the ER is able to translocate into the nucleus and bind to DNA to regulate the activity of different genes. However, it has additional functions independent of DNA binding; as hormone receptors for sex steroids, ERs, androgen receptors, progesterone receptors are important in sexual maturation and gestation. There are two different forms of the estrogen receptor referred to as α and β, each encoded by a separate gene. Hormone-activated estrogen receptors form dimers, since the two forms are coexpressed in many cell types, the receptors may form ERα or ERβ homodimers or ERαβ heterodimers. Estrogen receptor alpha and beta show significant overall sequence homology, both are composed of five domains designated A/B through F.
The N-terminal A/B domain is able to transactivate gene transcription in the absence of bound ligand. While this region is able to activate gene transcription without ligand, this activation is weak and more selective compared to the activation provided by the E domain; the C domain known as the DNA-binding domain, binds to estrogen response elements in DNA. The D domain is a hinge region that connects the E domains; the E domain contains the ligand binding cavity as well as binding sites for coactivator and corepressor proteins. The E-domain in the presence of bound ligand is able to activate gene transcription; the C-terminal F domain function is not clear and is variable in length. Due to alternative RNA splicing, several ER isoforms are known to exist. At least three ERα and five ERβ isoforms have been identified; the ERβ isoforms receptor subtypes can transactivate transcription only when a heterodimer with the functional ERß1 receptor of 59 kDa is formed. The ERß3 receptor was detected at high levels in the testis.
The two other ERα isoforms are 46kDa. Only in fish, but not in humans, an ERγ receptor has been described. In humans, the two forms of the estrogen receptor are encoded by different genes, ESR1 and ESR2 on the sixth and fourteenth chromosome, respectively. Both ERs are expressed in different tissue types, however there are some notable differences in their expression patterns: The ERα is found in endometrium, breast cancer cells, ovarian stromal cells, the hypothalamus. In males, ERα protein is found in the epithelium of the efferent ducts; the expression of the ERβ protein has been documented in ovarian granulosa cells, brain, heart, intestinal mucosa and endothelial cells. The ERs are regarded to be cytoplasmic receptors in their unliganded state, but visualization research has shown that only a small fraction of the ERs reside in the cytoplasm, with most ER constitutively in the nucleus; the "ERα" primary transcript gives rise to several alternatively spliced variants of unknown function. Endogenous estrogens Natural estrogens Synthetic estrogens Phytoestrogens Selective estrogen receptor modulators Antiestrogens The ER's helix 12 domain plays a crucial role in determining interactions with coactivators and corepressors and, the respective agonist or antagonist effect of the ligand.
Different ligands may differ in their affinity for alpha and beta isoforms of the estrogen receptor: estradiol binds well to both receptors estrone, raloxifene bind preferentially to the alpha receptor estriol, genistein to the beta receptorSubtype selective estrogen receptor modulators preferentially bind to either the α- or the β-subtype of the receptor. In addition, the different estrogen receptor combinations may respond differently to various ligands, which may translate into tissue selective agonistic and antagonistic effects; the ratio of α- to β- subtype concentration has been proposed to play a role in certain diseases. The concept of selective estrogen receptor modulators is based on the ability to promote ER interactions with different proteins such as transcriptional coactivator or corepressors. Furthermore, the ratio of coactivator to corepressor protein varies in different tissues; as a consequence, the same ligand may be an agonist in some tissue while antagonistic in other tissues.
Tamoxifen, for example, is an antagonist in breast and is, used as a breast cancer treatment but an ER agonist in bone and a partial agonist in the endometrium. Since estrogen is a steroidal hormone, it can pass through the phospholipid membranes of the cell, receptors therefore do not need to be membrane-bound in order to bind with estrogen. In the absence of hormone, estrogen receptors are located in the cytosol. Hormone binding to the receptor triggers a number of events starting with migration of the receptor from the cytosol into the nucleus, dimerization of the receptor, subsequent binding of the recepto
Pleasure is a broad class of mental states that humans and other animals experience as positive, enjoyable, or worth seeking. It includes more specific mental states such as happiness, enjoyment and euphoria; the early psychological concept of pleasure, the pleasure principle, describes it as a positive feedback mechanism that motivates the organism to recreate the situation it has just found pleasurable, to avoid past situations that caused pain. The experience of pleasure is subjective and different individuals experience different kinds and amounts of pleasure in the same situation. Many pleasurable experiences are associated with satisfying basic biological drives, such as eating, hygiene and sex; the appreciation of cultural artifacts and activities such as art, music and literature is pleasurable. Based upon the incentive salience model of reward – the attractive and motivational property of a stimulus that induces approach behavior and consummatory behavior – an intrinsic reward has two components: a "wanting" or desire component, reflected in approach behavior, a "liking" or pleasure component, reflected in consummatory behavior.
While all pleasurable stimuli are rewards, some rewards do not evoke pleasure. Pleasure is a component of reward. Stimuli that are pleasurable, therefore attractive, are known as intrinsic rewards, whereas stimuli that are attractive and motivate approach behavior, but are not inherently pleasurable, are termed extrinsic rewards. Extrinsic rewards are rewarding as a result of a learned association with an intrinsic reward. In other words, extrinsic rewards function as motivational magnets that elicit "wanting", but not "liking" reactions once they have been acquired; the reward system contains pleasure centers or hedonic hotspots – i.e. brain structures that mediate pleasure or "liking" reactions from intrinsic rewards. As of October 2017, hedonic hotspots have been identified in subcompartments within the nucleus accumbens shell, ventral pallidum, parabrachial nucleus, orbitofrontal cortex, insular cortex; the hotspot within the nucleus accumbens shell is located in the rostrodorsal quadrant of the medial shell, while the hedonic coldspot is located in a more posterior region.
The posterior ventral pallidum contains a hedonic hotspot, while the anterior ventral pallidum contains a hedonic coldspot. Microinjections of opioids and orexin are capable of enhancing liking in these hotspots; the hedonic hotspots located in the anterior OFC and posterior insula have been demonstrated to respond to orexin and opioids, as has the overlapping hedonic coldspot in the anterior insula and posterior OFC. On the other hand, the parabrachial nucleus hotspot has only been demonstrated to respond to benzodiazepine receptor agonists. Hedonic hotspots are functionally linked, in that activation of one hotspot results in the recruitment of the others, as indexed by the induced expression of c-Fos, an immediate early gene. Furthermore, inhibition of one hotspot results in the blunting of the effects of activating another hotspot. Therefore, the simultaneous activation of every hedonic hotspot within the reward system is believed to be necessary for generating the sensation of an intense euphoria.
Pleasure is considered one of the core dimensions of emotion. It can be described as the positive evaluation that forms the basis for several more elaborate evaluations such as "agreeable" or "nice"; as such, pleasure is an affect and not an emotion, as it forms one component of several different emotions. Pleasure is sometimes subdivided into fundamental pleasures that are related to survival and higher-order pleasures; the clinical condition of being unable to experience pleasure from enjoyable activities is called anhedonia. An active aversion to obtaining pleasure is called hedonophobia. Pleasure is regarded as a bipolar construct, meaning that the two ends of the spectrum from pleasant to unpleasant are mutually exclusive; this view is e.g. inherent in the circumplex model of affect. Yet, some lines of research suggest that people do experience pleasant and unpleasant feelings at the same time, giving rise to so-called mixed feelings; the degree to which something or someone is experienced as pleasurable not only depends on its objective attributes, but on beliefs about its history, about the circumstances of its creation, about its rarity, fame, or price, on other non-intrinsic attributes, such as the social status or identity it conveys.
For example, a sweater, worn by a celebrity is more desired than an otherwise identical sweater that has not, though less so if it has been washed. Another example was when Grammy-winning, internationally acclaimed violinist Joshua Bell played in the Washington D. C. subway for 43 minutes, attracting little attention from the 1,097 people who passed by, earning about $59 in tips. Paul Bloom describes these phenomena as arising from a form of essentialism. Epicurus and his followers defined the highest pleasure as the absence of suffering and pleasure itself as "freedom from pain in the body and freedom from turmoil in the soul". According to Cicero Epicurus believed that pleasure was the chief good and pain the chief evil. In the 12th century Razi's "Treatise of the Self and the Spirit" analyzed different types of pleasure and intellectual, explained their relations with one another, he concludes that human needs and desires are endless, "their
Testosterone is the primary male sex hormone and an anabolic steroid. In male humans, testosterone plays a key role in the development of male reproductive tissues such as testes and prostate, as well as promoting secondary sexual characteristics such as increased muscle and bone mass, the growth of body hair. In addition, testosterone is involved in health and well-being, the prevention of osteoporosis. Insufficient levels of testosterone in men may lead to abnormalities including frailty and bone loss. Testosterone is a steroid from the androstane class containing a keto and hydroxyl groups at the three and seventeen positions respectively, it is biosynthesized in several steps from cholesterol and is converted in the liver to inactive metabolites. It exerts its action through binding to and activation of the androgen receptor. In humans and most other vertebrates, testosterone is secreted by the testicles of males and, to a lesser extent, the ovaries of females. On average, in adult males, levels of testosterone are about 7 to 8 times as great as in adult females.
As the metabolism of testosterone in males is more pronounced, the daily production is about 20 times greater in men. Females are more sensitive to the hormone. In addition to its role as a natural hormone, testosterone is used as a medication, for instance in the treatment of low testosterone levels in men and breast cancer in women. Since testosterone levels decrease as men age, testosterone is sometimes used in older men to counteract this deficiency, it is used illicitly to enhance physique and performance, for instance in athletes. In general, androgens such as testosterone promote protein synthesis and thus growth of tissues with androgen receptors. Testosterone can be described as having anabolic effects. Anabolic effects include growth of muscle mass and strength, increased bone density and strength, stimulation of linear growth and bone maturation. Androgenic effects include maturation of the sex organs the penis and the formation of the scrotum in the fetus, after birth a deepening of the voice, growth of facial hair and axillary hair.
Many of these fall into the category of male secondary sex characteristics. Testosterone effects can be classified by the age of usual occurrence. For postnatal effects in both males and females, these are dependent on the levels and duration of circulating free testosterone. Effects before birth are divided into two categories, classified in relation to the stages of development; the first period occurs between 6 weeks of the gestation. Examples include genital virilisation such as midline fusion, phallic urethra, scrotal thinning and rugation, phallic enlargement. There is development of the prostate gland and seminal vesicles. During the second trimester, androgen level is associated with sex formation; this period affects the femininization or masculinization of the fetus and can be a better predictor of feminine or masculine behaviours such as sex typed behaviour than an adult's own levels. A mother's testosterone level during pregnancy is correlated with her daughter's sex-typical behavior as an adult, the correlation is stronger than with the daughter's own adult testosterone level.
Early infancy androgen effects are the least understood. In the first weeks of life for male infants, testosterone levels rise; the levels remain in a pubertal range for a few months, but reach the detectable levels of childhood by 4–7 months of age. The function of this rise in humans is unknown, it has been theorized that brain masculinization is occurring since no significant changes have been identified in other parts of the body. The male brain is masculinized by the aromatization of testosterone into estrogen, which crosses the blood–brain barrier and enters the male brain, whereas female fetuses have α-fetoprotein, which binds the estrogen so that female brains are not affected. Before puberty effects of rising androgen levels occur in both girls; these include adult-type body odor, increased oiliness of skin and hair, pubarche, axillary hair, growth spurt, accelerated bone maturation, facial hair. Pubertal effects begin to occur when androgen has been higher than normal adult female levels for months or years.
In males, these are usual late pubertal effects, occur in women after prolonged periods of heightened levels of free testosterone in the blood. The effects include:Growth of spermatogenic tissue in testicles, male fertility, penis or clitoris enlargement, increased libido and frequency of erection or clitoral engorgement occurs. Growth of jaw, brow and nose and remodeling of facial bone contours, in conjunction with human growth hormone occurs. Completion of bone maturation and termination of growth; this occurs indirectly via estradiol metabolites and hence more in men than women. Increased muscle strength and mass, shoulders become broader and rib cage expands, deepening of voice, growth of the Adam's apple. Enlargement of sebaceous glands; this might cause subcutaneous fat in face decreases. Pubic hair extends to thighs and up toward umbilicus, development of facial hair, loss of scalp hair, increase in chest hair, periareolar hair, perianal hair, leg hair, armpit hair. Testosterone is necessary for normal sperm development.
It activates genes in Sertoli cells. It regulates acute HPA response