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C (programming language) - Wikipedia, the free encyclopedia. CParadigm. Imperative (procedural), structured. Designed by. Dennis Ritchie. Developer. Dennis Ritchie & Bell Labs (creators); ANSI X3. J1. 1 (ANSI C); ISO/IEC JTC1/SC2. WG1. 4 (ISO C)First appeared. By design, C provides constructs that map efficiently to typical machine instructions, and therefore it has found lasting use in applications that had formerly been coded in assembly language, including operating systems, as well as various application software for computers ranging from supercomputers to embedded systems. C was originally developed by Dennis Ritchie between 1. Bell Labs. C has been standardized by the American National Standards Institute (ANSI) since 1. ANSI C) and subsequently by the International Organization for Standardization (ISO). C is an imperativeprocedural language. It was designed to be compiled using a relatively straightforward compiler, to provide low- level access to memory, to provide language constructs that map efficiently to machine instructions, and to require minimal run- time support. Therefore, C was useful for many applications that had formerly been coded in assembly language, for example in system programming. Despite its low- level capabilities, the language was designed to encourage cross- platform programming. A standards- compliant and portably written C program can be compiled for a very wide variety of computer platforms and operating systems with few changes to its source code. The language has become available on a very wide range of platforms, from embedded microcontrollers to supercomputers. Overview. In C, all executable code is contained within subroutines, which are called . The Texas Instruments TMX 1795: the (almost) first, forgotten microprocessor. FanDuel stats prove this Chelsea man is in the form of his life. Fichiers au format PDF. Easily Install/Try/UNINSTALL software in ZIPs PKZIP is not needed for basic ZIP operations. Is a free URL forwarding service (URL redirection) allowing anyone to take any existing URL and shorten it. Just type/paste a URL in the box below to shorten it and the short URL will forward to the long one. Help and Tutorials Customize Firefox Get Involved About Us. Bookmarks Bookmarks Toolbar Add bookmarks to this folder to see them displayed on the Bookmarks Toolbar Google Search the world's information.
Function parameters are always passed by value. Pass- by- reference is simulated in C by explicitly passing pointer values. C program source text is free- format, using the semicolon as a statement terminator and curly braces for grouping blocks of statements. The C language also exhibits the following characteristics: There is a small, fixed number of keywords, including a full set of flow of control primitives: for, if/else, while, switch, and do/while. There is one namespace, and user- defined names are not distinguished from keywords by any kind of sigil. There are a large number of arithmetical and logical operators, such as +, +=, ++, & , ~, etc. More than one assignment may be performed in a single statement. Function return values can be ignored when not needed. Typing is static, but weakly enforced: all data has a type, but implicit conversions can be performed; for instance, characters can be used as integers. Declarationsyntax mimics usage context. Unlike structs, arrays are not first- class objects; they cannot be assigned or compared using single built- in operators. They are not tagged, and are freely interconvertible with integers. Strings are not a separate data type, but are conventionally implemented as null- terminated arrays of characters. Low- level access to computer memory is possible by converting machine addresses to typed pointers. Procedures (subroutines not returning values) are a special case of function, with an untyped return type void. Functions may not be defined within the lexical scope of other functions. Function and data pointers permit ad hocrun- time polymorphism. A preprocessor performs macro definition, source code file inclusion, and conditional compilation. There is a basic form of modularity: files can be compiled separately and linked together, with control over which functions and data objects are visible to other files via static and extern attributes. Complex functionality such as I/O, string manipulation, and mathematical functions are consistently delegated to library routines. While C does not include some features found in some other languages, such as object orientation or garbage collection, such features can be implemented or emulated in C, often by way of external libraries (e. Boehm garbage collector or the GLib Object System). Relations to other languages. These languages have drawn many of their control structures and other basic features from C. Most of them (with Python being the most dramatic exception) are also very syntactically similar to C in general, and they tend to combine the recognizable expression and statement syntax of C with underlying type systems, data models, and semantics that can be radically different. History. Eventually, they decided to port the operating system to a PDP- 1. The original PDP- 1. Unix was developed in assembly language. The developers were considering rewriting the system using the B language, Thompson's simplified version of BCPL. Earlier instances include the Multics system which was written in PL/I), and Master Control Program (MCP) for the Burroughs B5. ALGOL in 1. 96. 1. In around 1. 97. 7, Ritchie and Stephen C. Johnson made further changes to the language to facilitate portability of the Unix operating system. Johnson's Portable C Compiler served as the basis for several implementations of C on new platforms. The version of C that it describes is commonly referred to as K& R C. The second edition of the book. Separate tools such as Unix's lint utility were developed that (among other things) could check for consistency of function use across multiple source files. In the years following the publication of K& R C, several features were added to the language, supported by compilers from AT& T (in particular PCC. These included: The large number of extensions and lack of agreement on a standard library, together with the language popularity and the fact that not even the Unix compilers precisely implemented the K& R specification, led to the necessity of standardization. ANSI C and ISO C. X3. J1. 1 based the C standard on the Unix implementation; however, the non- portable portion of the Unix C library was handed off to the IEEEworking group 1. POSIX standard. In 1. C standard was ratified as ANSI X3. This version of the language is often referred to as ANSI C, Standard C, or sometimes C8. In 1. 99. 0, the ANSI C standard (with formatting changes) was adopted by the International Organization for Standardization (ISO) as ISO/IEC 9. C9. 0. Therefore, the terms . National adoption of an update to the international standard typically occurs within a year of ISO publication. One of the aims of the C standardization process was to produce a superset of K& R C, incorporating many of the subsequently introduced unofficial features. The standards committee also included several additional features such as function prototypes (borrowed from C++), void pointers, support for international character sets and locales, and preprocessor enhancements. Although the syntax for parameter declarations was augmented to include the style used in C++, the K& R interface continued to be permitted, for compatibility with existing source code. C8. 9 is supported by current C compilers, and most C code being written today is based on it. Any program written only in Standard C and without any hardware- dependent assumptions will run correctly on any platform with a conforming C implementation, within its resource limits. Without such precautions, programs may compile only on a certain platform or with a particular compiler, due, for example, to the use of non- standard libraries, such as GUI libraries, or to a reliance on compiler- or platform- specific attributes such as the exact size of data types and byte endianness. In cases where code must be compilable by either standard- conforming or K& R C- based compilers, the . In 1. 99. 5, Normative Amendment 1 to the 1. C standard (ISO/IEC 9. AMD1: 1. 99. 5, known informally as C9. It has since been amended three times by Technical Corrigenda. Many of these had already been implemented as extensions in several C compilers. C9. 9 is for the most part backward compatible with C9. GCC, Solaris Studio, and other C compilers now support many or all of the new features of C9. The C compiler in Microsoft Visual C++, however, implements the C8. C9. 9 that are required for compatibility with C++1. The C standards committee adopted guidelines to limit the adoption of new features that had not been tested by existing implementations. The C1. 1 standard adds numerous new features to C and the library, including type generic macros, anonymous structures, improved Unicode support, atomic operations, multi- threading, and bounds- checked functions. It also makes some portions of the existing C9. C++. It includes a number of features not available in normal C, such as fixed- point arithmetic, named address spaces, and basic I/O hardware addressing. C has a formal grammar specified by the C standard. Comments may appear either between the delimiters /* and */, or (since C9. Comments delimited by /* and */ do not nest, and these sequences of characters are not interpreted as comment delimiters if they appear inside string or character literals. Function definitions, in turn, contain declarations and statements. Declarations either define new types using keywords such as struct, union, and enum, or assign types to and perhaps reserve storage for new variables, usually by writing the type followed by the variable name. Keywords such as char and int specify built- in types. Sections of code are enclosed in braces (. The most common statement is an expression statement, consisting of an expression to be evaluated, followed by a semicolon; as a side effect of the evaluation, functions may be called and variables may be assigned new values. To modify the normal sequential execution of statements, C provides several control- flow statements identified by reserved keywords. Structured programming is supported by if(- else) conditional execution and by do- while, while, and for iterative execution (looping). The for statement has separate initialization, testing, and reinitialization expressions, any or all of which can be omitted. Joint Implementation Team. 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While every effort has been made to ensure information provided on this website is accurate, no responsibility is accepted for any errors which may be present. Yeast metacaspase (Yca1p) is required for the execution of apoptosis upon a wide range of stimuli. However, the specific degradome of this yeast protease has not been unraveled so far. By combining different. Type or paste a DOI name into the text box. Your browser will take you to a Web page (URL) associated with that DOI name. Send questions or comments to [email protected]. Further documentation is available here. Q: What are the functions of each ingredient? Tribulus terrestris is used to enhance. Activation of the mitochondrial caspase pathway and subsequent calpain activation in monkey RPE cells cultured under zinc depletion. Eye (2. 01. 4) 2. November 2. 01. 3Top of page. Introduction. The retinal pigment epithelium (RPE) is an outer, single layer of cells overlaying the neural retina. RPE functions include formation of the outer blood–retinal barrier, transport of nutrients to photoreceptors, stabilization of the ion composition in the sub- retinal space, transport and storage of retinoids, phagocytosis and degradation of spent outer segments, protection against light and free radicals, and production of growth factors. Apoptosis (programmed cell death) is the genetically controlled ablation of cells during normal development. Inappropriately regulated apoptosis is implicated in disease states such as Alzheimer disease, stroke and cancer. Nearly 5 million Americans have heart failure today, with an incidence approaching population among persons older than 65 years of age. Heart failure is the reason for at least 20 percent of all hospital admissions. These complex RPE functions are essential for visual function. Abnormalities of RPE and Bruch’s membrane lead to macular degeneration characterized by a progressive loss of the central vision. Age- related macular degeneration (AMD) is the principle cause of incurable blindness throughout the world. The two types of AMD are the dry and wet forms, a classification based on the absence or presence of choroidal neovascularization (CNV). CNV is comprised of newly formed, immature blood vessels growing from the choroid to the outer retina. Patients typically first develop dry AMD, which is considered a risk factor or a precursor state for wet AMD. In the early stage of AMD, insoluble extracellular aggregates (drusen) accumulate in the retina. Later stage dry AMD is characterized by geographic atrophy, which is scattered or confluent areas of degenerated RPE cells. These degenerated RPE cells overlay the photoreceptors that rely on the RPE for trophic support. In later stage wet AMD, the CNV vessels leak fluid below or into the retina. SiRNAs targeting caspase-3 and/or caspase-7 prevent LPS-induced increase of iNOS expression (a, b) in cultured BV2 cells. In addition, caspase-3 or caspase-7 silencing prevents LPS-induced activation of NF- Microglia home page at microglia.net; The Role of Microglia in the Central Nervous System — Clinical Microbiology Reviews October 2004, p. 4; Creeping into your Head - A Brief Introduction to Microglia. Roitt’s Essential Immunology. Roitt's essential immunology 12th ed. Roitt’s Essential Immunology. The major risk factors for the early stage of AMD include: smoking, low dietary intake of anti- oxidants, and possibly low levels of zinc. These risk factors might cause loss of phagocytosis by the RPE and accumulation of toxic retinal debris which lead to dry AMD. RPE stress leads to CNV in wet AMD. Knowledge of the molecular mechanisms underlying wet AMD has led to several robust FDA- approved therapies. However, treatment of wet AMD does not typically ameliorate RPE damage,4 and inhibition of the initial stage of the RPE cell damage would be of major benefit in the treatment of AMD. A detailed molecular mechanism for RPE cell death is lacking. It is known that Oral zinc supplementation ameliorates some symptoms in human AMD. The membrane- permeable zinc chelator N,N,N',N. Experimental animals were handled in accordance with the ARVO statement for the Use of Animals in Ophthalmic and Vision Research and with the Guiding Principles in the Care and Use of Animals (DHEW Publication, NIH 8. Monkey eyes were utilized because they are similar to human but can be obtained more quickly after death, thus minimizing post- mortem metabolic changes. The average time between death and dissection was less than 1 h. Primary culture of RPE cells. Monkey RPE cells were cultured using Tamada’s method for human RPE cells. Briefly, fresh eyecups were quartered, the retinas were removed, and the remaining RPE/choroid samples were incubated in 2. Roche Applied Science, Indianapolis, IN, USA). The RPE cells were collected by pipetting, washed in a solution containing 2. U penicillin and 2. The cells were trypsinized before passage. The cells from passage 3 were plated at 1. RPE cells reached 1. Figure 1). Zinc depletion, ER stress, and activation of death receptor pathways. Chelation of zinc ion was performed by adding 3 . The time dependent experiment was performed and reported in the Supplementary Information. When used, 1. 0 or 1. Images were captured with an Axiovert 2. Axio. Cam MRm camera (Carl Zeiss Vision Gmbh, Hallbergmoos, Germany). The images were processed with Image. J 1. 4. 2 (National Institutes of Health, Bethesda, MD, USA) and Photoshop (Adobe Systems Inc., San Jose, CA, USA). Fas ligand (EMD Chemicals, Billerica, MA, USA) at 1. TNF. Ten micrometer thapsigargin (Santa Cruz Biotechnology, Inc., Santa Cruz, CA, USA) was used as a positive control for caspase- 1. ER stress. A caspase- 1. ATAD (R& D systems, Inc.) was used at 1. Protein concentrations were measured by the BCA assay (Thermo Fisher Scientific Inc., Rockford, IL, USA) with bovine serum albumin standards. For immunoblotting, equal amounts of the proteins were loaded and run on 4–1. Nu. PAGE gels with MES or MOPs buffers (Life Technologies). The proteins were electrotransferred to PVDF membrane at 1. V for 1 h. The membranes were probed with primary antibodies to calpain- 1 (Thermo Fisher Scientific), calpain- 2, . Secondary antibodies, conjugated to alkaline phosphatase or to horseradish peroxidase were visualized with BCIP/NBT (Bio- Rad Laboratories, Hercules, CA, USA) or by chemiluminescence (Amersham ECL Plus, GE Healthcare Biosciences, Piscataway, NJ, USA). Band intensities were measured with Image. J 1. 4. 0 (NIH, Bethesda, MD, USA). To compensate for staining variability between the membranes, densities of the bands were normalized to the density of . Statistical analyses were performed by Dunnett’s t- test (JMP 8. Statistical Software, SAS Institute Inc., Cary, NC, USA). Three independent experiments from different cultures were conducted for all the studies. We certify that all applicable institutional and governmental regulations concerning the ethical use of animals were followed during this research. Top of page. Results. Caspase and calpain activation in zinc depletion. In the TPEN- treated cells, endogenous pro- caspase 3 at 3. Da was proteolyzed to an active 1. Da fragment. 1. 2 A smaller active caspase- 3 fragment at 1. Da, which is known to form the active caspase- 3 hetero- dimer with an 1. Da fragment,1. 2 was not detected. Known inactive caspase- 3 fragments at 2. Da caused by calpain. Figure 2a, lanes 1 and 2). Immunoblots of caspases, calpains, and their substrates: (lane 1) normal, (lane 2) 2- day 3 . The 8. 0- k. Da catalytic subunit of high calcium- requiring calpain- 2 did not appear to change with TPEN treatment (Figure 2e, lanes 1 and 2). However, because the active, N- terminal truncated form of calpain- 2 migrates to nearly the same position as the intact 8. Da calpain- 2 on SDS- PAGE,1. Da band in lane 2 probably contained both intact and autolyzed calpain- 2. In support of this, autolyzed calpain- 2 at 4. Da increased. The zinc depletion also caused a loss of the intact 2. Da . This leads to a significant accumulation of a calpain- specific 1. Da fragment (P=0. Da fragment (P=0. These results showed that 3 . Adding SNJ- 1. 94. VAD together did not further protect the cells (Figure 3e), suggesting that either calpain or caspase- 3 is up- stream of the other. We found that the z- VAD partially inhibited the calpain- 1 and - 2 activation as well as the caspase activation (Figures 2a–g), although the z- VAD did not inhibit accumulation of the calpain- specific 1. Da . Calpain inhibitor SNJ- 1. Figures 2a–g) and only weakly inhibited the calpain- 1 activation. Phase- contrast micrographs of monkey RPE cells: (a) 2- day normal, (b) 3 . This lead to accumulation of a caspase- 3- specific breakdown product at 8. Da (a marker of apoptosis,1. The calpain- specific 7. Da breakdown product of PARP was not observed even when calpain was activated. Since the calpain and caspase inhibitors were both able to partially inhibit the TPEN- induced morphologic damage at a similar rate (Figures 3c and d), cell death by the TPEN may be due to apoptosis and necrosis by action of calpain and caspase. Densitometric analysis showed: significant inhibition of the accumulation of the calpain- specific 1. Da SBDP by the calpain inhibitor (SNJ 1. Vimentin is expressed in primate RPE cells in vivo only under pathologic conditions but is expressed in culture. The loss of the cytokeratin- 1. P=0. 0. 01, n=3). One hundred micrometer SNJ- 1. VAD promoted full recovery of the intact bands for both vimentin and cytokeratin- 1. The accumulation of caspase- 3- specific cytokeratin- 1. Da was fully inhibited by the z- VAD (lanes 5 and 6). SNJ- 1. 94. 5 did not inhibit production of the 2. Da band (lanes 3 and 4). Caspase- 8 death receptor and caspase- 1. ER stress pathways. Caspases (including caspase- 8) or calpains were not activated by up to 5. Fas ligand or TNF. As a positive control, stress inducer 1. An ER membrane marker, calnexin, decreased after the thapsigargin treatment (Figure 4e). CHOP and Bi. P levels in our experiments increased with the thapsigargin treatment (Figures 4f and g). The caspase- 1. 2 inhibitor ATAD inhibited the caspase- 1. ER stress (lane 3). Using our monkey model of RPE cell death, the present studies showed that: (1) cytosolic calpains are activated (confirming previous studies in human cells. ER stress and death receptor pathways are not involved in TPEN- induced damage. We speculate that a major mechanism for the TPEN damage in the current study was zinc deficiency. However, note that in addition to zinc, TPEN chelates other heavy metal ions (eg copper and iron). Manganese is a key component of mitochondrial superoxide dismutase 2, and manganese deficiency causes cell damage in the RPE. The AREDS (Age- Related Eye Disease Study) 6 shows that reduced zinc and copper are risk factors for AMD. Thus, deficiency of other metal ions might also contribute to the observed RPE cell damage. Caspase activation generally indicates apoptotic cell death. The fact that initiator caspase- 9, and effecter caspases- 3 and - 7 were activated by our TPEN treatments also suggests that the RPE cell damage is caused by damage to mitochondria. As indicated in the summary of pathways involved in TPEN- induced cell death (Figure 5), initial zinc deficiency may have caused early mitochondrial damage by oxidative stress. This was supported by the fact that zinc is a co- factor for Cu–Zn superoxide dismutase. Adequate zinc also induces the synthesis of cysteine- rich metallothionein, a hydroxyl radical scavenger. |
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