The pharmaceutical industry discovers, develops and markets drugs or pharmaceutical drugs for use as medications to be administered to patients to cure them, vaccinate them, or alleviate a symptom. Pharmaceutical companies may deal in medical devices, they are subject to a variety of laws and regulations that govern the patenting, safety and marketing of drugs. The modern pharmaceutical industry traces its roots to two sources; the first of these were local apothecaries that expanded from their traditional role distributing botanical drugs such as morphine and quinine to wholesale manufacture in the mid 1800s. Rational drug discovery from plants started with the isolation of morphine and sleep-inducing agent from opium, by the German apothecary assistant Friedrich Sertürner who named the compound after the Greek god of dreams, Morpheus. By the late 1880s, German dye manufacturers had perfected the purification of individual organic compounds from tar and other mineral sources and had established rudimentary methods in organic chemical synthesis.
The development of synthetic chemical methods allowed scientists to systematically vary the structure of chemical substances, growth in the emerging science of pharmacology expanded their ability to evaluate the biological effects of these structural changes. By the 1890s, the profound effect of adrenal extracts on many different tissue types had been discovered, setting off a search both for the mechanism of chemical signalling and efforts to exploit these observations for the development of new drugs; the blood pressure raising and vasoconstrictive effects of adrenal extracts were of particular interest to surgeons as hemostatic agents and as treatment for shock, a number of companies developed products based on adrenal extracts containing varying purities of the active substance. In 1897, John Abel of Johns Hopkins University identified the active principle as epinephrine, which he isolated in an impure state as the sulfate salt. Industrial chemist Jokichi Takamine developed a method for obtaining epinephrine in a pure state, licensed the technology to Parke-Davis.
Parke-Davis marketed epinephrine under the trade name Adrenalin. Injected epinephrine proved to be efficacious for the acute treatment of asthma attacks, an inhaled version was sold in the United States until 2011. By 1929 epinephrine had been formulated into an inhaler for use in the treatment of nasal congestion. While effective, the requirement for injection limited the use of epinephrine and orally active derivatives were sought. A structurally similar compound, was identified by Japanese chemists in the Ma Huang plant and marketed by Eli Lilly as an oral treatment for asthma. Following the work of Henry Dale and George Barger at Burroughs-Wellcome, academic chemist Gordon Alles synthesized amphetamine and tested it in asthma patients in 1929; the drug proved to have only modest anti-asthma effects, but produced sensations of exhilaration and palpitations. Amphetamine was developed by Smith and French as a nasal decongestant under the trade name Benzedrine Inhaler. Amphetamine was developed for the treatment of narcolepsy, post-encephalitic parkinsonism, mood elevation in depression and other psychiatric indications.
It received approval as a New and Nonofficial Remedy from the American Medical Association for these uses in 1937 and remained in common use for depression until the development of tricyclic antidepressants in the 1960s. In 1903, Hermann Emil Fischer and Joseph von Mering disclosed their discovery that diethylbarbituric acid, formed from the reaction of diethylmalonic acid, phosphorus oxychloride and urea, induces sleep in dogs; the discovery was patented and licensed to Bayer pharmaceuticals, which marketed the compound under the trade name Veronal as a sleep aid beginning in 1904. Systematic investigations of the effect of structural changes on potency and duration of action led to the discovery of phenobarbital at Bayer in 1911 and the discovery of its potent anti-epileptic activity in 1912. Phenobarbital was among the most used drugs for the treatment of epilepsy through the 1970s, as of 2014, remains on the World Health Organizations list of essential medications; the 1950s and 1960s saw increased awareness of the addictive properties and abuse potential of barbiturates and amphetamines and led to increasing restrictions on their use and growing government oversight of prescribers.
Today, amphetamine is restricted to use in the treatment of attention deficit disorder and phenobarbital in the treatment of epilepsy. A series of experiments performed from the late 1800s to the early 1900s revealed that diabetes is caused by the absence of a substance produced by the pancreas. In 1869, Oskar Minkowski and Joseph von Mering found that diabetes could be induced in dogs by surgical removal of the pancreas. In 1921, Canadian professor Frederick Banting and his student Charles Best repeated this study, found that injections of pancreatic extract reversed the symptoms produced by pancreas removal. Soon, the extract was demonstrated to work in people, but development of insulin therapy as a routine medical procedure was delayed by difficulties in producing the material in sufficient quantity and with reproducible purity; the researchers sought assistance from industrial collaborators at Eli Lilly and Co. based on the company's experience with large scale purification of biological materials.
Chemist George B. Walden of Eli Lilly and Company found that careful adjustment of the pH of the extract allowed a pure grade of insulin to be produced. Under pressure from Toronto Un
International Standard Serial Number
An International Standard Serial Number is an eight-digit serial number used to uniquely identify a serial publication, such as a magazine. The ISSN is helpful in distinguishing between serials with the same title. ISSN are used in ordering, interlibrary loans, other practices in connection with serial literature; the ISSN system was first drafted as an International Organization for Standardization international standard in 1971 and published as ISO 3297 in 1975. ISO subcommittee TC 46/SC 9 is responsible for maintaining the standard; when a serial with the same content is published in more than one media type, a different ISSN is assigned to each media type. For example, many serials are published both in electronic media; the ISSN system refers to these types as electronic ISSN, respectively. Conversely, as defined in ISO 3297:2007, every serial in the ISSN system is assigned a linking ISSN the same as the ISSN assigned to the serial in its first published medium, which links together all ISSNs assigned to the serial in every medium.
The format of the ISSN is an eight digit code, divided by a hyphen into two four-digit numbers. As an integer number, it can be represented by the first seven digits; the last code digit, which may be 0-9 or an X, is a check digit. Formally, the general form of the ISSN code can be expressed as follows: NNNN-NNNC where N is in the set, a digit character, C is in; the ISSN of the journal Hearing Research, for example, is 0378-5955, where the final 5 is the check digit, C=5. To calculate the check digit, the following algorithm may be used: Calculate the sum of the first seven digits of the ISSN multiplied by its position in the number, counting from the right—that is, 8, 7, 6, 5, 4, 3, 2, respectively: 0 ⋅ 8 + 3 ⋅ 7 + 7 ⋅ 6 + 8 ⋅ 5 + 5 ⋅ 4 + 9 ⋅ 3 + 5 ⋅ 2 = 0 + 21 + 42 + 40 + 20 + 27 + 10 = 160 The modulus 11 of this sum is calculated. For calculations, an upper case X in the check digit position indicates a check digit of 10. To confirm the check digit, calculate the sum of all eight digits of the ISSN multiplied by its position in the number, counting from the right.
The modulus 11 of the sum must be 0. There is an online ISSN checker. ISSN codes are assigned by a network of ISSN National Centres located at national libraries and coordinated by the ISSN International Centre based in Paris; the International Centre is an intergovernmental organization created in 1974 through an agreement between UNESCO and the French government. The International Centre maintains a database of all ISSNs assigned worldwide, the ISDS Register otherwise known as the ISSN Register. At the end of 2016, the ISSN Register contained records for 1,943,572 items. ISSN and ISBN codes are similar in concept. An ISBN might be assigned for particular issues of a serial, in addition to the ISSN code for the serial as a whole. An ISSN, unlike the ISBN code, is an anonymous identifier associated with a serial title, containing no information as to the publisher or its location. For this reason a new ISSN is assigned to a serial each time it undergoes a major title change. Since the ISSN applies to an entire serial a new identifier, the Serial Item and Contribution Identifier, was built on top of it to allow references to specific volumes, articles, or other identifiable components.
Separate ISSNs are needed for serials in different media. Thus, the print and electronic media versions of a serial need separate ISSNs. A CD-ROM version and a web version of a serial require different ISSNs since two different media are involved. However, the same ISSN can be used for different file formats of the same online serial; this "media-oriented identification" of serials made sense in the 1970s. In the 1990s and onward, with personal computers, better screens, the Web, it makes sense to consider only content, independent of media; this "content-oriented identification" of serials was a repressed demand during a decade, but no ISSN update or initiative occurred. A natural extension for ISSN, the unique-identification of the articles in the serials, was the main demand application. An alternative serials' contents model arrived with the indecs Content Model and its application, the digital object identifier, as ISSN-independent initiative, consolidated in the 2000s. Only in 2007, ISSN-L was defined in the
Laboratory Virtual Instrument Engineering Workbench is a system-design platform and development environment for a visual programming language from National Instruments. The graphical language is named "G". Released for the Apple Macintosh in 1986, LabVIEW is used for data acquisition, instrument control, industrial automation on a variety of operating systems, including Microsoft Windows, various versions of Unix and macOS; the latest versions of LabVIEW are LabVIEW 2018 and LabVIEW NXG 3.0, released in November 2018. The programming paradigm used in LabVIEW, sometimes called G, is based on data availability. If there is enough data available to a subVI or function, that subVI or function will execute. Execution flow is determined by the structure of a graphical block diagram on which the programmer connects different function-nodes by drawing wires; these wires propagate variables and any node can execute as soon as all its input data become available. Since this might be the case for multiple nodes LabVIEW can execute inherently in parallel.
Multi-processing and multi-threading hardware is exploited automatically by the built-in scheduler, which multiplexes multiple OS threads over the nodes ready for execution. LabVIEW integrates the creation of user interfaces into the development cycle. LabVIEW programs-subroutines are termed virtual instruments; each VI has three components: a block diagram, a front panel, a connector pane. The last is used to represent the VI in the block diagrams of other; the front panel is built using indicators. Controls are inputs: they allow a user to supply information to the VI. Indicators are outputs: they indicate, or display, the results based on the inputs given to the VI; the back panel, a block diagram, contains the graphical source code. All of the objects placed on the front panel will appear on the back panel as terminals; the back panel contains structures and functions which perform operations on controls and supply data to indicators. The structures and functions can be placed on the back panel.
Collectively controls, indicators and functions are referred to as nodes. Nodes are connected to one another using wires, e.g. two controls and an indicator can be wired to the addition function so that the indicator displays the sum of the two controls. Thus a virtual instrument can be run as either a program, with the front panel serving as a user interface, or, when dropped as a node onto the block diagram, the front panel defines the inputs and outputs for the node through the connector pane; this implies each VI can be tested before being embedded as a subroutine into a larger program. The graphical approach allows nonprogrammers to build programs by dragging and dropping virtual representations of lab equipment with which they are familiar; the LabVIEW programming environment, with the included examples and documentation, makes it simple to create small applications. This is a benefit on one side, but there is a certain danger of underestimating the expertise needed for high-quality G programming.
For complex algorithms or large-scale code, it is important that a programmer possess an extensive knowledge of the special LabVIEW syntax and the topology of its memory management. The most advanced LabVIEW development systems offer the ability to build stand-alone applications. Furthermore, it is possible to create distributed applications, which communicate by a client–server model, are thus easier to implement due to the inherently parallel nature of G. Applications in LabVIEW are designed using well-known architectures, known as design patterns; the most common design patterns for graphical LabVIEW applications are listed in the table below. LabVIEW includes extensive support for interfacing to devices, instruments and other devices. Users interface to hardware by either writing direct bus commands or using high-level, device-specific, drivers that provide native LabVIEW function nodes for controlling the device. LabVIEW includes built-in support for NI hardware platforms such as CompactDAQ and CompactRIO, with a large number of device-specific blocks for such hardware, the Measurement and Automation eXplorer and Virtual Instrument Software Architecture toolsets.
National Instruments makes thousands of device drivers available for download on the NI Instrument Driver Network. LabVIEW includes a compiler; this aids performance. The graphical code is translated into executable machine code by a compiler; the LabVIEW syntax is enforced during the editing process and compiled into the executable machine code when requested to run or upon saving. In the latter case, the executable and the source code are merged into a single file; the executable runs with the help of the LabVIEW run-time engine, which contains some pre-compiled code to perform common tasks that are defined by the G language. The run-time engine reduces compiling time and provides a consistent interface to various operating systems, graphic systems, hardware components, etc; the run-time environment makes the code portable across platforms. LabVIEW code can be slower than equivalent compiled C code, although the differences lie more with program optimization than inherent execution speed. Many libraries with a large number of functions for data acquisition, signal generation, statistics, signal conditioning, etc. along with numerous for functions such as integration and other specialized abilities associated with data capture from hardware sensor
A software house is a company whose primary products are various forms of software, software technology and software product development. Software houses are companies in the software industry. There are a number of different types of software houses: Large and well-known companies producing Commercial off-the-shelf, such as Microsoft, SAP AG, Oracle Corporation, HP, Adobe Systems and Red Hat Smaller companies that produce custom software for other companies and entrepreneurs, such as RIKSOF Companies producing specialized Commercial off-the-shelf software, such as Panorama, Siebel Systems, GazitIT, Enigma Technologies Companies producing Software as a Service SaaS, such as Google, LinkedIn Companies producing software components, such as Developer Express, ComponentOne and Sohn Software Application Service Provider such as Salesforce Companies producing bespoke software for vertical industries or particular geographical regionsAll of these may be categorized in one or many of the following: contractual - when the software house is contracted to deliver some particular software from outside product development - when it produces ready to use, packaged software.
For example, having sub-teams spread in different time zones may allow a 24-hour company working day, if the teams and procedures are well established. A good example is the test team in time zone 8 hours ahead or behind the development team, who fix software bugs found by the testers. A professional software house consists of at least three dedicated sub-teams: Business analysts who define the business needs of the market Software developers who create the technical specification and write the software Software testers who are responsible for the whole process of quality managementIn bigger software houses, greater specialization is employed, quite there are also: Technical writers who write all the documentation such as user guides Release specialists who are responsible for building the whole product and software versioning User experience designers, who are creating the design architecture based on business requirements, user research and expertise in usability Graphic designers who are responsible for the design of the graphical user interface.
Maintenance engineers who are behind two, three or more lines of support Consultants responsible for making the solution operational if some specialist knowledge is necessary. Examples of this include: building multidimensional cubes in business intelligence software, integrating with existing solutions, implementing business scenarios in Business Process Management software. In September 2017, Allegion collaborated with Software House to extend electronic access control options; the manager of a software house is called the Head Of Development, reports to the stakeholders. He or she leads the sub-teams directly or via the managers/leaders depending on the size of the organization. Teams of up to 10 person are the most operational. In bigger organizations, there are in general two models of the hierarchy: All the teams are independent and they work separately on the different projects; the structure is quite simple and all the employees reports to one person, what make the situation quite clear however it is not a good solution in terms of knowledge exchange and optimal usage of human resources.
In this model there are dedicated managers/leaders for each main specialization, "renting" their people for particular projects led by product/project managers, who formally or informally buy the people and pay for their time. This leads to each private employee having two bosses – the product/project manager and the specialized "resource" manager. On one hand it optimizes the usage of human resources, on the other hand it may give rise to conflicts about which one manager has priority in the structure. There are a number of variants of these structures, a number of organizations have this structure spread and split within various departments and units. Software house may use a number of various methodologies to produce the code; these can include: the waterfall model, including project management methodologies like PRINCE2 or PMBoK agile software development, such as Extreme Programming and SCRUMThere are some methodologies which combine both, such as the spiral model, Rational Unified Process or MSF.
Regardless of the methodology used, the product life cycle always consists of at least three stages: Design – including both the business and technical specification Coding – the development itself Testing – the quality managementEach stage ideally takes 30% of the total time, with the remaining 10% in reserve. The UML sequence diagram of interaction between these groups may look like: At each stage a different group plays a key role, however each type of role must be involved throughout the whole development process: Analysts, after completing the business specification, manage the changing business situation to minimize the possibility of change over time, they support both programmers and testers during the whole development process to ensure that the final product fulfills the business needs specified at the start. The process ideally puts business analysts as the key players during final delivery of the solution to the customer, as they are best placed to provide the best business layer.
Programmers do the technical specification during the design phase, why they are called programmers/designers, during testing time they fix bugs. Testers complete the test scenarios during the design phase, evaluate them d
San Diego is a city in the U. S. state of California. It is in San Diego County, on the coast of the Pacific Ocean in Southern California 120 miles south of Los Angeles and adjacent to the border with Mexico. With an estimated population of 1,419,516 as of July 1, 2017, San Diego is the eighth-largest city in the United States and second-largest in California, it is part of the San Diego–Tijuana conurbation, the second-largest transborder agglomeration between the U. S. and a bordering country after Detroit–Windsor, with a population of 4,922,723 people. The city is known for its mild year-round climate, natural deep-water harbor, extensive beaches, long association with the United States Navy, recent emergence as a healthcare and biotechnology development center. San Diego has been called "the birthplace of California". Home to the Kumeyaay people, it was the first site visited by Europeans on what is now the West Coast of the United States. Upon landing in San Diego Bay in 1542, Juan Rodríguez Cabrillo claimed the area for Spain, forming the basis for the settlement of Alta California 200 years later.
The Presidio and Mission San Diego de Alcalá, founded in 1769, formed the first European settlement in what is now California. In 1821, San Diego became part of the newly independent Mexico, which reformed as the First Mexican Republic two years later. California became part of the United States in 1848 following the Mexican–American War and was admitted to the union as a state in 1850; the city is the seat of San Diego County and is the economic center of the region as well as the San Diego–Tijuana metropolitan area. San Diego's main economic engines are military and defense-related activities, international trade, manufacturing; the presence of the University of California, San Diego, with the affiliated UCSD Medical Center, has helped make the area a center of research in biotechnology. The original inhabitants of the region are now known as the San La Jolla people; the area of San Diego has been inhabited by the Kumeyaay people. The first European to visit the region was explorer Juan Rodríguez Cabrillo, sailing under the flag of Castile but born in Portugal.
Sailing his flagship San Salvador from Navidad, New Spain, Cabrillo claimed the bay for the Spanish Empire in 1542, named the site "San Miguel". In November 1602, Sebastián Vizcaíno was sent to map the California coast. Arriving on his flagship San Diego, Vizcaíno surveyed the harbor and what are now Mission Bay and Point Loma and named the area for the Catholic Saint Didacus, a Spaniard more known as San Diego de Alcalá. On November 12, 1602, the first Christian religious service of record in Alta California was conducted by Friar Antonio de la Ascensión, a member of Vizcaíno's expedition, to celebrate the feast day of San Diego. Permanent colonization of California and of San Diego began in 1769 with the arrival of four contingents of Spaniards from New Spain and the Baja California peninsula. Two seaborne parties reached San Diego Bay: the San Carlos, under Vicente Vila and including as notable members the engineer and cartographer Miguel Costansó and the soldier and future governor Pedro Fages, the San Antonio, under Juan Pérez.
An initial overland expedition to San Diego from the south was led by the soldier Fernando Rivera and included the Franciscan missionary and chronicler Juan Crespí, followed by a second party led by the designated governor Gaspar de Portolà and including the mission president Junípero Serra. In May 1769, Portolà established the Fort Presidio of San Diego on a hill near the San Diego River, it was the first settlement by Europeans in. In July of the same year, Mission San Diego de Alcalá was founded by Franciscan friars under Serra. By 1797, the mission boasted the largest native population in Alta California, with over 1,400 neophytes living in and around the mission proper. Mission San Diego was the southern anchor in Alta California of the historic mission trail El Camino Real. Both the Presidio and the Mission are National Historic Landmarks. In 1821, Mexico won its independence from Spain, San Diego became part of the Mexican territory of Alta California. In 1822, Mexico began its attempt to extend its authority over the coastal territory of Alta California.
The fort on Presidio Hill was abandoned, while the town of San Diego grew up on the level land below Presidio Hill. The Mission was secularized by the Mexican government in 1834, most of the Mission lands were granted to former soldiers; the 432 residents of the town petitioned the governor to form a pueblo, Juan María Osuna was elected the first alcalde, defeating Pío Pico in the vote. However, San Diego had been losing population throughout the 1830s and in 1838 the town lost its pueblo status because its size dropped to an estimated 100 to 150 residents. Beyond town Mexican land grants expanded the number of California ranchos that modestly added to the local economy. Americans gained increased awareness of California, its commercial possibilities, from the writings of two countrymen involved in the officially forbidden, to foreigners, but economically significant hide and tallow trade, where San Diego was a major port and the only one with an adequate harbor: William Shaler's "Journal of a Voyage Between China and the North-Western Coast of America, Made in 1804" and Richard Henry Dana's more substantial and convincing account, of his 1834–36 voyage, the classic Two Years Before the Mast.
In 1846, the United States went to war against Mexico and sent a naval and land expedition to conquer Alta California. At firs