Ye Chen-Izu, Bence Hegyi, Zhong Jian, Balazs Horvath, John A Shaw, Tamas Banyasz, Leighton T Izu
Cardiac arrhythmias are associated with various forms of heart diseases. Ventricular arrhythmias present a significant risk for sudden cardiac death. Atrial fibrillations predispose to blood clots leading to stroke and heart attack. Scientists have been developing patch-clamp technology to study ion channels and action potentials (APs) underlying cardiac excitation and arrhythmias. Beyond the traditional patch-clamp techniques, innovative new techniques were developed for studying complex arrhythmia mechanisms. Here we review the recent development of methods including AP-Clamp, Dynamic Clamp, AP-Clamp Sequential Dissection, and Patch-Clamp-in-Gel. These methods provide powerful tools for researchers to decipher how the dynamic systems in excitation-Ca2+ signaling-contraction feedforward and feedback to control cardiac function and how their dysregulations lead to heart diseases.
{"title":"INNOVATIVE TECHNIQUES AND NEW INSIGHTS: Studying cardiac ionic currents and action potentials in physiologically relevant conditions.","authors":"Ye Chen-Izu, Bence Hegyi, Zhong Jian, Balazs Horvath, John A Shaw, Tamas Banyasz, Leighton T Izu","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Cardiac arrhythmias are associated with various forms of heart diseases. Ventricular arrhythmias present a significant risk for sudden cardiac death. Atrial fibrillations predispose to blood clots leading to stroke and heart attack. Scientists have been developing patch-clamp technology to study ion channels and action potentials (APs) underlying cardiac excitation and arrhythmias. Beyond the traditional patch-clamp techniques, innovative new techniques were developed for studying complex arrhythmia mechanisms. Here we review the recent development of methods including AP-Clamp, Dynamic Clamp, AP-Clamp Sequential Dissection, and Patch-Clamp-in-Gel. These methods provide powerful tools for researchers to decipher how the dynamic systems in excitation-Ca<sup>2+</sup> signaling-contraction feedforward and feedback to control cardiac function and how their dysregulations lead to heart diseases.</p>","PeriodicalId":74449,"journal":{"name":"Physiological mini-reviews","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10722976/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138814041","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Advanced age and amyotrophic lateral sclerosis (ALS) are both associated with a loss of motor neurons resulting in muscle fiber atrophy and muscle weakness. Aging associated muscle fiber atrophy and weakening is termed sarcopenia, but the association with motor neuron loss is not as clearly established as in ALS, probably related to the prolonged time course of aging-related changes. Although aging and ALS effects on limb muscle strength and neuromotor performance are serious, such effects on the diaphragm muscle can be life threatening. Converging evidence indicates that larger phrenic motor neurons, innervating more fatigable type IIx and/or IIb diaphragm muscle fibers (fast fatigue intermediate, FInt and fast fatigable, FF motor units) are more susceptible to degeneration with both aging and ALS compared to smaller phrenic motor neurons innervating type I and IIa diaphragm muscle fibers (slow and fast fatigue resistant motor units, respectively). The etiology of ALS and age-related loss of motor neurons appears to involve mitochondrial function and neuroinflammation, both chronic and acute exacerbation. How mitochondrial dysfunction, neuroinflammation and motor neuron size intersect is the focus of continuing investigation.
{"title":"MOTOR NEURON LOSS IN AGING AND AMYOTROPHIC LATERAL SCLEROSIS: DIFFERENT FUSE LENGTHS, SAME EXPLOSION.","authors":"Matthew J Fogarty, Alyssa D Brown, Gary C Sieck","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Advanced age and amyotrophic lateral sclerosis (ALS) are both associated with a loss of motor neurons resulting in muscle fiber atrophy and muscle weakness. Aging associated muscle fiber atrophy and weakening is termed sarcopenia, but the association with motor neuron loss is not as clearly established as in ALS, probably related to the prolonged time course of aging-related changes. Although aging and ALS effects on limb muscle strength and neuromotor performance are serious, such effects on the diaphragm muscle can be life threatening. Converging evidence indicates that larger phrenic motor neurons, innervating more fatigable type IIx and/or IIb diaphragm muscle fibers (fast fatigue intermediate, FInt and fast fatigable, FF motor units) are more susceptible to degeneration with both aging and ALS compared to smaller phrenic motor neurons innervating type I and IIa diaphragm muscle fibers (slow and fast fatigue resistant motor units, respectively). The etiology of ALS and age-related loss of motor neurons appears to involve mitochondrial function and neuroinflammation, both chronic and acute exacerbation. How mitochondrial dysfunction, neuroinflammation and motor neuron size intersect is the focus of continuing investigation.</p>","PeriodicalId":74449,"journal":{"name":"Physiological mini-reviews","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10416778/pdf/nihms-1921849.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10003026","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sophisticated design aids are available to help automate microprogram development both for large, complex computers and for micro-processor-based systems. These aids include procedures for source code verification, object code generation, microprogram simulation, and interactive debugging. For various reasons, such aids are generally not well-developed for microprogrammable minicomputers. This paper describes a microprogramming laboratory developed for the Interdata 85 minicomputer which uses both the minicomputer itself as well as the time-sharing and batch facilities of a large computer center. Experience with the laboratory has shown that the facility for interacting with a microprogram is as important as the availability of complete diagnostic information. The argument is made that design automation aids for microprogramming minicomputers could be produced efficiently from standardized assembly and simulation programs.
{"title":"A microprogramming design laboratory","authors":"C. Vickery","doi":"10.1145/1164881.1164897","DOIUrl":"https://doi.org/10.1145/1164881.1164897","url":null,"abstract":"Sophisticated design aids are available to help automate microprogram development both for large, complex computers and for micro-processor-based systems. These aids include procedures for source code verification, object code generation, microprogram simulation, and interactive debugging. For various reasons, such aids are generally not well-developed for microprogrammable minicomputers. This paper describes a microprogramming laboratory developed for the Interdata 85 minicomputer which uses both the minicomputer itself as well as the time-sharing and batch facilities of a large computer center. Experience with the laboratory has shown that the facility for interacting with a microprogram is as important as the availability of complete diagnostic information. The argument is made that design automation aids for microprogramming minicomputers could be produced efficiently from standardized assembly and simulation programs.","PeriodicalId":74449,"journal":{"name":"Physiological mini-reviews","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1976-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73949721","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
A FORTRAN compiler is being developed to aid in writing systems and application programs for minicomputers. The compiler is machine-independent in the sense that it can be made to generate code for a new machine with relatively little effort. The FORTRAN language accepted by the compiler is extended to facilitate the writing of "systems" programs. Particular emphasis is placed on optimization of the generated code for efficiency of storage utilization.
{"title":"Optimized machine-independent extended FORTRAN for minicomputer programming","authors":"Gordon Bennett-Novak","doi":"10.1145/1164881.1164886","DOIUrl":"https://doi.org/10.1145/1164881.1164886","url":null,"abstract":"A FORTRAN compiler is being developed to aid in writing systems and application programs for minicomputers. The compiler is machine-independent in the sense that it can be made to generate code for a new machine with relatively little effort. The FORTRAN language accepted by the compiler is extended to facilitate the writing of \"systems\" programs. Particular emphasis is placed on optimization of the generated code for efficiency of storage utilization.","PeriodicalId":74449,"journal":{"name":"Physiological mini-reviews","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1976-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86327151","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Personal experiences are reported of the difficulties and the successes associated with attempts to develop mathematical software for small computers. Examples are used to illustrate the process of algorithm selection and program "squeezing." Some unforeseen advantages of the resulting programs are mentioned.
{"title":"Experiences in the development of mathematical software for small computers","authors":"J. Nash","doi":"10.1145/1164881.1164894","DOIUrl":"https://doi.org/10.1145/1164881.1164894","url":null,"abstract":"Personal experiences are reported of the difficulties and the successes associated with attempts to develop mathematical software for small computers. Examples are used to illustrate the process of algorithm selection and program \"squeezing.\" Some unforeseen advantages of the resulting programs are mentioned.","PeriodicalId":74449,"journal":{"name":"Physiological mini-reviews","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1976-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88119600","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Reduced hardware costs have made high level languages for minicomputers a necessity. A survey of some of the languages available. (FORTRAN, BASIC, FOCAL, PL-11, C, SPL, MPL, PLM, and BCPL) demonstrates the current need for a simple, portable, and readable minicomputer language.
{"title":"Minicomputer programming languages","authors":"W. Gorman, Michael Broussard","doi":"10.1145/1164881.1164882","DOIUrl":"https://doi.org/10.1145/1164881.1164882","url":null,"abstract":"Reduced hardware costs have made high level languages for minicomputers a necessity. A survey of some of the languages available. (FORTRAN, BASIC, FOCAL, PL-11, C, SPL, MPL, PLM, and BCPL) demonstrates the current need for a simple, portable, and readable minicomputer language.","PeriodicalId":74449,"journal":{"name":"Physiological mini-reviews","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1976-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80365312","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
In a small computer system, it is not unusual to write a BASIC program which is too large to fit into main memory. Such a program must be replaced by a collection of overlay modules together with inter-module sequencing logic. A sophisticated BASIC interpreter allows this sequencing to be done under program control. Unless carefully managed, a decomposition can produce an environment where programs exhibit undesirable characteristics. A structuring and design strategy is presented, discussed, and illustrated by a typical business application. Attention is given to program production, efficiency, reliability, maintainability, and modifiability using this strategy.
{"title":"Structuring basic programs for managing overlays in a small computer system","authors":"Ted Cary","doi":"10.1145/1164881.1164892","DOIUrl":"https://doi.org/10.1145/1164881.1164892","url":null,"abstract":"In a small computer system, it is not unusual to write a BASIC program which is too large to fit into main memory. Such a program must be replaced by a collection of overlay modules together with inter-module sequencing logic. A sophisticated BASIC interpreter allows this sequencing to be done under program control. Unless carefully managed, a decomposition can produce an environment where programs exhibit undesirable characteristics. A structuring and design strategy is presented, discussed, and illustrated by a typical business application. Attention is given to program production, efficiency, reliability, maintainability, and modifiability using this strategy.","PeriodicalId":74449,"journal":{"name":"Physiological mini-reviews","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1976-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87715505","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
EDUCOMP's Time-shared Operating System (ETOS) is an integrated package of hardware and software designed for maximum utility of a PDP8 computer. ETOS supports up to 16 users, with each user able to use the system as if he were operating on a stand-alone PDP8 with 64K bytes of memory.This paper will contrast the various modes of computer operation and illustrate how the combination of batch, real-time, and interactive usage results in the optimum fulfillment of the all-important criterion of price/performance.Emphasis is placed on the maintenance of continuous system performance. This is especially important to the educational user. In many situations, if the machine must be shut down for one type of user, the educational user is the first one to be sacrificed. Computer assisted instruction, drills, simulations, and general student motivation are somehow viewed as less important than the use of the computer to collect taxes. ETOS is EDUCOMP's solution to this misguided allocation of resources.ETOS requires a 16K omnibus PDP8, clock, an RK8e controller with an RK05 drive, a backup peripheral for the RK05 drive, and a Time Share Control Module.
{"title":"ETOS: multi-lingual time sharing system for the PDP8","authors":"Thomas Schreier","doi":"10.1145/1164881.1164898","DOIUrl":"https://doi.org/10.1145/1164881.1164898","url":null,"abstract":"EDUCOMP's Time-shared Operating System (ETOS) is an integrated package of hardware and software designed for maximum utility of a PDP8 computer. ETOS supports up to 16 users, with each user able to use the system as if he were operating on a stand-alone PDP8 with 64K bytes of memory.This paper will contrast the various modes of computer operation and illustrate how the combination of batch, real-time, and interactive usage results in the optimum fulfillment of the all-important criterion of price/performance.Emphasis is placed on the maintenance of continuous system performance. This is especially important to the educational user. In many situations, if the machine must be shut down for one type of user, the educational user is the first one to be sacrificed. Computer assisted instruction, drills, simulations, and general student motivation are somehow viewed as less important than the use of the computer to collect taxes. ETOS is EDUCOMP's solution to this misguided allocation of resources.ETOS requires a 16K omnibus PDP8, clock, an RK8e controller with an RK05 drive, a backup peripheral for the RK05 drive, and a Time Share Control Module.","PeriodicalId":74449,"journal":{"name":"Physiological mini-reviews","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1976-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84079810","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ASM/GEN and SIM/GEN are a software system comprised of a set of independent FORTRAN program writer modules designed to generate micro computer and small minicomputer assemblers and simulators. It is simple enough to be used by those with limited architecture and programming backgrounds, but flexible and powerful enough to generate efficient and well-structured assemblers and simulators for small micro/mini computers with sophisticated architectures and instruction sets. This paper presents a brief description of the generating system, the generated assemblers and simulators and the advantages they offer in both programming and pedagogical applications.
{"title":"The automated generation of cross-system software for supporting micro/mini computer systems","authors":"G. Johnson, R. A. Mueller","doi":"10.1145/1164881.1164887","DOIUrl":"https://doi.org/10.1145/1164881.1164887","url":null,"abstract":"ASM/GEN and SIM/GEN are a software system comprised of a set of independent FORTRAN program writer modules designed to generate micro computer and small minicomputer assemblers and simulators. It is simple enough to be used by those with limited architecture and programming backgrounds, but flexible and powerful enough to generate efficient and well-structured assemblers and simulators for small micro/mini computers with sophisticated architectures and instruction sets. This paper presents a brief description of the generating system, the generated assemblers and simulators and the advantages they offer in both programming and pedagogical applications.","PeriodicalId":74449,"journal":{"name":"Physiological mini-reviews","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1976-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90297008","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
PL-11 is a programming language for the PDP-11 family of computers designed and implemented as part of the OMEGA Project at CERN (the European Organization for Nuclear Research). Its purpose is to provide an effective tool for both physicists and systems programmers to use in building real-time data acquisition systems that are online to high-energy physics experiments. It is a fairly typical member of the PL-class of programming languages (44) which are based on the initial design of PL360 (41) (See Table 1). Each of these languages represents a linguistic model of its specific machine architecture, thereby providing a Systems Implementation Language (SIL) that is extremely efficient on its target machine, yet is also highly effective for human programmers to use. The need for such a tool is obvious on all computer systems, but especially on minicomputers, where most applications are in fact "systems programs". For example, in any data acquisition environment the distinction between "user" and "operating system" largely disappears---the user's prime concern is to handle time-dependent sequences of events involving the manipulation of special I/O devices through direct status checking and data streaming---all functions which are usually buried in the operating system of conventional computing systems.
{"title":"Experience in the design, implementation and use of PL-11, a programming language for the PDP-11","authors":"R. Russell","doi":"10.1145/1164881.1164884","DOIUrl":"https://doi.org/10.1145/1164881.1164884","url":null,"abstract":"PL-11 is a programming language for the PDP-11 family of computers designed and implemented as part of the OMEGA Project at CERN (the European Organization for Nuclear Research). Its purpose is to provide an effective tool for both physicists and systems programmers to use in building real-time data acquisition systems that are online to high-energy physics experiments. It is a fairly typical member of the PL-class of programming languages (44) which are based on the initial design of PL360 (41) (See Table 1). Each of these languages represents a linguistic model of its specific machine architecture, thereby providing a Systems Implementation Language (SIL) that is extremely efficient on its target machine, yet is also highly effective for human programmers to use. The need for such a tool is obvious on all computer systems, but especially on minicomputers, where most applications are in fact \"systems programs\". For example, in any data acquisition environment the distinction between \"user\" and \"operating system\" largely disappears---the user's prime concern is to handle time-dependent sequences of events involving the manipulation of special I/O devices through direct status checking and data streaming---all functions which are usually buried in the operating system of conventional computing systems.","PeriodicalId":74449,"journal":{"name":"Physiological mini-reviews","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1976-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73109607","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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