New Zealand is a sovereign island country in the southwestern Pacific Ocean. The country geographically comprises two main landmasses—the North Island, the South Island —and around 600 smaller islands. New Zealand is situated some 2,000 kilometres east of Australia across the Tasman Sea and 1,000 kilometres south of the Pacific island areas of New Caledonia and Tonga; because of its remoteness, it was one of the last lands to be settled by humans. During its long period of isolation, New Zealand developed a distinct biodiversity of animal and plant life; the country's varied topography and its sharp mountain peaks, such as the Southern Alps, owe much to the tectonic uplift of land and volcanic eruptions. New Zealand's capital city is Wellington. Sometime between 1250 and 1300, Polynesians settled in the islands that were named New Zealand and developed a distinctive Māori culture. In 1642, Dutch explorer Abel Tasman became the first European to sight New Zealand. In 1840, representatives of the United Kingdom and Māori chiefs signed the Treaty of Waitangi, which declared British sovereignty over the islands.
In 1841, New Zealand became a colony within the British Empire and in 1907 it became a dominion. Today, the majority of New Zealand's population of 4.9 million is of European descent. Reflecting this, New Zealand's culture is derived from Māori and early British settlers, with recent broadening arising from increased immigration; the official languages are English, Māori, NZ Sign Language, with English being dominant. A developed country, New Zealand ranks in international comparisons of national performance, such as quality of life, education, protection of civil liberties, economic freedom. New Zealand underwent major economic changes during the 1980s, which transformed it from a protectionist to a liberalised free-trade economy; the service sector dominates the national economy, followed by the industrial sector, agriculture. Nationally, legislative authority is vested in an elected, unicameral Parliament, while executive political power is exercised by the Cabinet, led by the prime minister Jacinda Ardern.
Queen Elizabeth II is the country's monarch and is represented by a governor-general Dame Patsy Reddy. In addition, New Zealand is organised into 11 regional councils and 67 territorial authorities for local government purposes; the Realm of New Zealand includes Tokelau. New Zealand is a member of the United Nations, Commonwealth of Nations, ANZUS, Organisation for Economic Co-operation and Development, ASEAN Plus Six, Asia-Pacific Economic Cooperation, the Pacific Community and the Pacific Islands Forum. Dutch explorer Abel Tasman sighted New Zealand in 1642 and named it Staten Land "in honour of the States General", he wrote, "it is possible that this land joins to the Staten Land but it is uncertain", referring to a landmass of the same name at the southern tip of South America, discovered by Jacob Le Maire in 1616. In 1645, Dutch cartographers renamed the land Nova Zeelandia after the Dutch province of Zeeland. British explorer James Cook subsequently anglicised the name to New Zealand. Aotearoa is the current Māori name for New Zealand.
It is unknown whether Māori had a name for the whole country before the arrival of Europeans, with Aotearoa referring to just the North Island. Māori had several traditional names for the two main islands, including Te Ika-a-Māui for the North Island and Te Waipounamu or Te Waka o Aoraki for the South Island. Early European maps labelled the islands North and South. In 1830, maps began to use North and South to distinguish the two largest islands and by 1907 this was the accepted norm; the New Zealand Geographic Board discovered in 2009 that the names of the North Island and South Island had never been formalised, names and alternative names were formalised in 2013. This set the names as North Island or Te Ika-a-Māui, South Island or Te Waipounamu. For each island, either its English or Māori name can be used. New Zealand was one of the last major landmasses settled by humans. Radiocarbon dating, evidence of deforestation and mitochondrial DNA variability within Māori populations suggest New Zealand was first settled by Eastern Polynesians between 1250 and 1300, concluding a long series of voyages through the southern Pacific islands.
Over the centuries that followed, these settlers developed a distinct culture now known as Māori. The population was divided into iwi and hapū who would sometimes cooperate, sometimes compete and sometimes fight against each other. At some point a group of Māori migrated to Rēkohu, now known as the Chatham Islands, where they developed their distinct Moriori culture; the Moriori population was all but wiped out between 1835 and 1862 because of Taranaki Māori invasion and enslavement in the 1830s, although European diseases contributed. In 1862 only 101 survived, the last known full-blooded Moriori died in 1933; the first Europeans known to have reached New Zeala
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.
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
Sympathomimetic drugs are stimulant compounds which mimic the effects of endogenous agonists of the sympathetic nervous system. The primary endogenous agonists of the sympathetic nervous system are the catecholamines, which function as both neurotransmitters and hormones. Sympathomimetic drugs are used to treat cardiac arrest and low blood pressure, or delay premature labor, among other things; these drugs can act through several mechanisms, such as directly activating postsynaptic receptors, blocking breakdown and reuptake of certain neurotransmitters, or stimulating production and release of catecholamines. The mechanisms of sympathomimetic drugs can be direct-acting, such as α-adrenergic agonists, β-adrenergic agonists, dopaminergic agonists. For maximum sympathomimetic activity, a drug must have: Amine group two carbons away from an aromatic group A hydroxyl group at the chiral beta position in the R-configuration Hydroxyl groups in the meta and para position of the aromatic ring to form a catechol, essential for receptor bindingThe structure can be modified to alter binding.
If the amine is primary or secondary, it will have direct action, but if the amine is tertiary, it will have poor direct action. If the amine has bulky substituents it will have greater beta adrenergic receptor activity, but if the substituent is not bulky it will favor the alpha adrenergic receptors. Direct stimulation of the α- and β-adrenergic receptors can produce sympathomimetic effects. Salbutamol is a used direct-acting β2-agonist. Other examples include phenylephrine and dobutamine. Stimulation of the D1 receptor by dopaminergic agonists such as fenoldopam is used intravenously to treat hypertensive crisis. Dopaminergic stimulants such as amphetamine and propylhexedrine work by causing the release of dopamine and norepinephrine, along with blocking the reuptake of these neurotransmitters. A primary or secondary aliphatic amine separated by 2 carbons from a substituted benzene ring is minimally required for high agonist activity; the pKa of the amine is 8.5-10. The presence of hydroxy group in the benzene ring at 3rd and 4th position shows maximum alpha- and beta-adrenergic activity.
Substances such as cocaine affect dopamine, some substances such as MDMA affect serotonin. Norepinephrine is synthesized by the body from the amino acid tyrosine, is used in the synthesis of epinephrine, a stimulating neurotransmitter of the central nervous system. Thus, all sympathomimetic amines fall into the larger group of stimulants. In addition to intended therapeutic use, many of these stimulants have abuse potential, can induce tolerance, physical dependence, although not by the same mechanism as opioids or sedatives; the symptoms of physical withdrawal from stimulants can include fatigue, dysphoric mood, increased appetite, vivid or lucid dreams, hypersomnia or insomnia, increased movement or decreased movement and drug craving, as is apparent in the rebound withdrawal from certain substituted amphetamines. Physical withdrawal from some sedatives can be lethal, for instance benzodiazepine withdrawal syndrome. Opioid withdrawal is uncomfortable described as a bad case of the flu, with severe abdominal cramps and diarrhoea as central symptoms, but it is lethal unless the user has a comorbid condition.
"Parasympatholytic" and "sympathomimetic" have similar effects, but through different pathways. For example, both cause mydriasis, but parasympatholytics reduce accommodation while sympathomimetics do not. Amphetamine benzylpiperazine cathine cathinone cocaine ephedrine lisdexamfetamine maprotiline MDMA methamphetamine methcathinone methylenedioxypyrovalerone methylphenidate 4-methylaminorex oxymetazoline pemoline phenmetrazine propylhexedrine pseudoephedrine Sympathetic nervous system Sympatholytic Amines,+Sympathomimetic at the US National Library of Medicine Medical Subject Headings
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
A metered-dose inhaler is a device that delivers a specific amount of medication to the lungs, in the form of a short burst of aerosolized medicine, self-administered by the patient via inhalation. It is the most used delivery system for treating asthma, chronic obstructive pulmonary disease and other respiratory diseases; the medication in a metered dose inhaler is most a bronchodilator, corticosteroid or a combination of both for the treatment of asthma and COPD. Other medications less used but administered by MDI are mast cell stabilizers, such as cromoglicate or nedocromil. A metered-dose inhaler consists of three major components; the formulation itself is made up of the drug, a liquefied gas propellant and, in many cases, stabilising excipients. The actuator contains the mating discharge nozzle and includes a dust cap to prevent contamination. To use the inhaler the patient presses down on the top of the canister, with their thumb supporting the lower portion of the actuator. Actuation of the device releases a single metered dose of the formulation which contains the medication either dissolved or suspended in the propellant.
Breakup of the volatile propellant into droplets, followed by rapid evaporation of these droplets, results in the generation of an aerosol consisting of micrometer-sized medication particles that are inhaled. Metered-dose inhalers are only one type of inhaler, but they are the most used type; the replacement of chlorofluorocarbons propellants with hydrofluoroalkanes resulted in the redesign of metered-dose inhalers in the 1990s. For one variety of beclomethasone inhaler, this redesign resulted in smaller aerosol particles being produced, led to an increase of potency by a factor of 2.6. Asthma inhalers contain a medication. Nicotine inhalers allows cigarette smokers to get nicotine without using tobacco, much like nicotine gum or a nicotine patch; the US Food and Drug Administration has approved some nicotine inhaler product for smoking cessation. Nicotine inhalers that are marketed as nicotine replacement therapy should not be confused with electronic cigarettes, which produce an aerosol from a tobacco extract, using a heating coil, while nicotine inhalers produce a noncombusted nicotine aerosol.
A study found that "levels of carcinogens and toxins in e-cigarettes exceeded those measured in an FDA-approved nicotine inhaler". Nicotine inhalers are known by their nickname of “the puffer”; these devices are made of thin plastic, sometimes resembling a cylinder shape. They contain a porous nicotine-filled plug, located in the base of the product; when you puff on the inhaler, nicotine aerosol is absorbed in the mouth's lining. Every inhaler delivers four hundred puffs of this nicotine vapor; the nicotine inhaler is temperature sensitive. In cooler weather, less nicotine is delivered; the Nicotine Inhaler is considered easier to use than the electronic cigarette as it is disposable, contains fewer parts than the electronic cigarette. Dry powder inhalers involve micronised powder packaged in single dose quantities in blisters or gel capsules containing the powdered medication to be drawn into the lungs by the user's own breath; these systems tend to be more expensive than the MDI, patients with compromised lung function, such as occurs during an asthma attack, may find it difficult to generate enough airflow to get good function from them.
Metered-dose inhalers can be used to treat COPD, both during lung attacks. Before the invention of the MDI, asthma medication was delivered using a squeeze bulb nebulizer, fragile and unreliable; the crude nature of these devices meant that the particles that they generated were large, too large for effective drug delivery to the lungs. Nonetheless these nebulizers paved the way for inhalation drug delivery providing the inspiration for the MDI. MDIs were first developed in 1955 by Riker Laboratories, now a subsidiary of 3M Healthcare. At that time MDIs represented a convergence of two new technologies, the CFC propellant and the Meshburg metering valve, designed for dispensing perfume; the initial design by Riker used a glass canister coated with a vinyl plastic to improve its resilience. By 1956 Riker had developed two MDI based products, the Medihaler-Ept containing epinephrine and the Medihaler-Iso containing Isoprenaline. Both products are agonists which provide short term relief from asthma symptoms and have now been replaced in asthma treatment by salbutamol, more selective.
Metered-dose inhalers are sometimes used with add-on devices referred to as holding chambers or spacers, which are tubes attached to the inhaler that act as a reservoir or holding chamber and reduce the speed at which the aerosol enters the mouth. They serve to hold the medication, sprayed by the inhaler; this makes it easier to use the inhaler and helps ensure that more of the medication gets into the lungs instead of just into the mouth or the air. With proper use, a spacer can make an inhaler somewhat more effective in delivering medicine. Spacers can be helpful to adults and children who find a regular metered dose inhaler hard to use. People who use corticosteroid inhalers should use a spacer to prevent getting the medicine in th