scholarly journals Computer Simulations Predict High Structural Heterogeneity of Functional State of NMDA Receptors

2017 ◽  
Author(s):  
Anton V. Sinitskiy ◽  
Vijay S. Pande
Keyword(s):  
Nmda Receptors ◽  
Computer Simulations ◽  
Functional State ◽  
Structural Heterogeneity ◽  
Atomic Structures ◽  
The Past ◽  
Electrophysiological Recordings ◽  
Functional States

AbstractIt is unclear how the known atomic structures of neuronal NMDA receptors (NMDARs) relate to the functional states of NMDARs inferred from electrophysiological recordings. We address this problem by all-atom computer simulations, a method successfully applied in the past to much smaller biomolecules. Our simulations predict that four ‘non-active’ cryoEM structures of NMDARs rapidly interconvert on submicrosecond timescales, and therefore, correspond to the same functional state of the receptor.

Bioinformational significance of the past–present–future for integral assessment of the functional state of the human organism

2020 ◽  
Vol 15 (16) ◽  
pp. 99-107
Author(s):  
V. V. Kalnish ◽  
Keyword(s):  
Heart Rate ◽  
Functional State ◽  
Environmental Conditions ◽  
The Body ◽  
Human Organism ◽  
Probability Of Occurrence ◽  
Functional Relationships ◽  
The Past ◽  
Retrospective Assessment ◽  
Functional States

Introduction. Temporary processes take place not only in the consciousness of a person - the entire organism and its components at the unconscious level are also somehow oriented in time. In the process of evolution in living systems, a certain way of responding to the prevailing external and internal situations has been formed, in the process of implementation of which a fundamental restruc-turing of the functional relationships of its subsystems is carried out. Therefore, the characteristics of the behavior of an organism in time are fundamental and integral for assessing its state and the form of orientation in time. The objective of the undertaken research is to develop an approach to retrospective assessment of the functional state of a person, taking into account the processes that occur before and after the period of time designated as «present». Methods and scope of research. The rhythmogram data and the calculation of its indicators were obtained as a result of an annual daily study (333 measurements of 5-minute heart rate segments) using the gythmograph apparatus. For further analysis, a well-known set of heart rate indicators was used, as well as a number of its new «temporal» characteristics: a function of the probabilities of two events in the «past» relative to the «present» and a function of the probabilities of two events in the «future» relative to the «present». Results and Conclusions. The studies carried out have shown the novelty and expediency of a retrospective analysis of heart rate variability from the standpoint of isolating the body’s reactions to «past» and «future» functional states that change depending on the transformations of environmental conditions during the year. The attractiveness of such an analysis lies in the fact that the obtained functions of the probability of occurrence of events in the «past» and «future» reflect the fundamental processes of integra-tion of various physiological processes in the body. The specifics of providing rigid and plastic processes occurring in the human body, accompanying their synchronization in the event of changes in environmental conditions, have been established. The possibility of classifying functional states according to the characteristics of the functions of probability of occurrence of events in the «past» and «future» has been revealed. Key words: Functional state; Rhythmogram; Past; Present; Future.

Microscopic Identification of Surface Steps on SiC by Density-Functional Calculations

2020 ◽  
Vol 1004 ◽  
pp. 145-152
Author(s):  
Kaori Seino ◽  
Atsushi Oshiyama
Keyword(s):  
Experimental Observation ◽  
Density Functional Calculations ◽  
Density Functional ◽  
Atomic Steps ◽  
Atomic Structures ◽  
The Past ◽  
Microscopic Identification ◽  
Surface Steps ◽  
Inclined Surfaces ◽  
Lower Terrace

We have performed density-functional calculations in order to clarify atomic structures and energetics of surface steps on SiC. The obtained energetics of distinct step types on vicinal 3C-SiC(111) surfaces which correspond to 4H- and 6H-SiC(0001) surfaces reveals the atom-scale reason for the experimental observation in the past that the step morphology is straight for the SiC(0001) surfaces inclined toward the 〈1-100〉 direction while it is meandering for the 〈11-20〉 inclined surfaces. The calculations clarify the rebonding between upper- and lower-terrace edge atoms, which is decisive for the energetics of the atomic steps.

scholarly journals Structure Determination of Microtubules and Pili: Past, Present, and Future Directions

2022 ◽  
Vol 8 ◽  
Author(s):  
James A. Garnett ◽  
Joseph Atherton
Keyword(s):  
Ex Vivo ◽  
Structural Heterogeneity ◽  
Resonance Spectroscopy ◽  
Future Directions ◽  
Computational Approaches ◽  
The Past ◽  
Major Shift ◽  
Technical Innovations

Historically proteins that form highly polymeric and filamentous assemblies have been notoriously difficult to study using high resolution structural techniques. This has been due to several factors that include structural heterogeneity, their large molecular mass, and available yields. However, over the past decade we are now seeing a major shift towards atomic resolution insight and the study of more complex heterogenous samples and in situ/ex vivo examination of multi-subunit complexes. Although supported by developments in solid state nuclear magnetic resonance spectroscopy (ssNMR) and computational approaches, this has primarily been due to advances in cryogenic electron microscopy (cryo-EM). The study of eukaryotic microtubules and bacterial pili are good examples, and in this review, we will give an overview of the technical innovations that have enabled this transition and highlight the advancements that have been made for these two systems. Looking to the future we will also describe systems that remain difficult to study and where further technical breakthroughs are required.

Design and Analysis of Computer Experiments

2017 ◽  
pp. 264-279
Author(s):  
Xinwei Deng ◽  
Ying Hung ◽  
C. Devon Lin
Keyword(s):  
Complex Systems ◽  
Mathematical Models ◽  
Gaussian Process ◽  
Computer Simulations ◽  
Process Modeling ◽  
Computer Experiments ◽  
Space Filling ◽  
Science And Engineering ◽  
The Past ◽  
Statistical Approaches

Computer experiments refer to the study of complex systems using mathematical models and computer simulations. The use of computer experiments becomes popular for studying complex systems in science and engineering. The design and analysis of computer experiments have received broad attention in the past decades. In this chapter, we present several widely used statistical approaches for design and analysis of computer experiments, including space-filling designs and Gaussian process modeling. A special emphasis is given to recently developed design and modeling techniques for computer experiments with quantitative and qualitative factors.

scholarly journals From Blowing Wind to Running Water: Unifying Sediment Transport

Eos ◽  
2020 ◽  
Vol 101 ◽  
Author(s):  
Thomas P�htz ◽  
Abram Clark ◽  
Manousos Valyrakis ◽  
Orencio Dur�n
Keyword(s):  
Sediment Transport ◽  
Computer Simulations ◽  
Laboratory Experiments ◽  
Running Water ◽  
The Past ◽  
Oil Water

Laboratory experiments and grain-scale computer simulations during the past decade have led to a more universal understanding of flow-driven sediment transport across flows in oil, water, and air.

scholarly journals Review: NMDA Receptor Hypofunction and Its Involvement in Excitotoxicity in Schizophrenia

2017 ◽  
Vol 4 (1) ◽  
Author(s):  
Trevor M. Krysak
Keyword(s):  
Nmda Receptors ◽  
Glutamate Release ◽  
Psychiatric Condition ◽  
Dopaminergic Transmission ◽  
Glutamate Signaling ◽  
The Past ◽  
Dopamine Hypothesis ◽  
Subcortical Regions ◽  
The Brain ◽  
Underlying Pathogenesis

Schizophrenia is a severely debilitating psychiatric condition that has long been associated with altered neurotransmission in the brain, especially in dopaminergic transmission. The dopamine hypothesis of schizophrenia, while it has been the main focus of research in the past decades, fails to explain the underlying pathogenesis. A more recent hypothesis dealing with altered central glutamate signaling in schizophrenia may help to ameliorate the deficit in understanding. Blockade of the glutamatergic NMDA receptors produces schizophrenic behaviours and phenotypes almost indistinguishable from the disease itself in animal and human models. It has been elucidated that hypofunction of NMDA receptors on the parvalbumin-­‐containing interneurons in the cortex and subcortical regions leads to a downstream increase in cortical glutamate release, which may be causing functional connectivity issues through mechanisms of excitotoxicity. A number of studies have pointed to the hypofunction of these NMDA receptors leading to excitotoxicity and cellular degeneration, which may be implicated in the disease pathology. This review will evaluate and highlight this forthcoming evidence.

scholarly journals Increasing Discovery in Research, Design, and Other Processes with Artificial General Intelligence and General Collective Intelligence

2020 ◽  
Author(s):  
Andy E Williams
Keyword(s):  
State Space ◽  
Research Design ◽  
Functional State ◽  
Collective Intelligence ◽  
Human Cognition ◽  
General Intelligence ◽  
Problem Domain ◽  
Minimal Set ◽  
Business Operations ◽  
Functional States

Any system with repeatable behavior can potentially be defined with the minimal set of functions that might be composed to represent the entirety of that behavior. The states accessible through these functions then forms a “functional state space” through which the system moves. Since functional states spaces can be used to represent every problem domain from physics, to communications, to business operations, to the human cognition itself, a general approach to not only research but design and all other processes of discovery that is applicable to all domains can potentially be defined to radically increase capacity for discovery in each domain.

scholarly journals Analysis of current research in the field of detecting driver fatigue in the vehicle cab

2021 ◽  
pp. 19-36
Author(s):  
Alexandr O. Bulygin ◽  
◽  
Alexey M. Kashevnik ◽  
Keyword(s):  
Functional State ◽  
Continuous Monitoring ◽  
Dynamic Assessment ◽  
Driver Behavior ◽  
Neurophysiological Monitoring ◽  
Time Interval ◽  
Driver Fatigue ◽  
Work Training ◽  
Functional States ◽  
Impaired Attention

The article analyzes the methods of detecting driver fatigue which are described in modern literature. There are a great variety of methods for assessing the functional state of a person. A functional state is an integral set of characteristics of those functions and qualities of a person that directly or indirectly determine the performance of any activity. The physical and mental state of a person, the success of his work, training, creativity depends on the functional state of the organism. The assessment of dynamic driver behavior has become an increasingly popular area of research in recent years. Dynamic assessment of driver behavior includes continuous monitoring that allows you to determine functional states, in contrast to modern driver monitoring systems, which assess conditions such as drowsiness and impaired attention for a short (1-10 s) time interval. Such systems allow us to talk about physiological, but not neurophysiological monitoring, which allows monitoring the functional state of fatigue. Therefore, it makes sense to monitor the driver’s state of fatigue of, as well as to warn them in a timely manner to avoid collisions with other vehicles. In the article, a study was carried out and an analysis of the ways to obtain the appropriate characteristics from a person, with the help of which it is possible to determine his functional state of fatigue. As a result of the analysis of the sources, the most common methods for determining the functional state of the driver were selected. Further, the sources found were classified according to the most common methods for obtaining significant characteristics of the functional state of the driver. As a result, a comparative analysis was made, demonstrating the capabilities of modern systems of this class.

NMDA-receptor hypofunction versus excessive synaptic elimination as models of schizophrenia

2003 ◽  
Vol 26 (1) ◽  
pp. 92-92
Author(s):  
Ralph E. Hoffman ◽  
Thomas H. McGlashan
Keyword(s):  
Nmda Receptor ◽  
Nmda Receptors ◽  
Computer Simulations ◽  
Regulatory Role ◽  
Local Connectivity ◽  
Genetic Studies ◽  
Pathophysiological Role ◽  
Cortical Synapses ◽  
Synaptic Pruning

AbstractWe propose that the primary cause of schizophrenia is a pathological extension of synaptic pruning involving local connectivity that unfolds ordinarily during adolescence. Computer simulations suggest that this pathology provides reasonable accounts of a range of symptoms in schizophrenia, and is consistent with recent postmortem and genetic studies. NMDA-receptors play a regulatory role in maintaining and/or eliminating cortical synapses, and therefore may play a pathophysiological role.

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