scholarly journals Modelling modal gating of ion channels with hierarchical Markov models

2016 ◽  
Vol 472 (2192) ◽  
pp. 20160122 ◽  
Author(s):  
Ivo Siekmann ◽  
Mark Fackrell ◽  
Edmund J. Crampin ◽  
Peter Taylor
Keyword(s):  
Ion Channels ◽  
Markov Model ◽  
Time Course ◽  
Markov Models ◽  
Mode Switching ◽  
New Approach ◽  
Modelling Framework ◽  
Long Time ◽  
Modal Gating ◽  
Opening And Closing

Many ion channels spontaneously switch between different levels of activity. Although this behaviour known as modal gating has been observed for a long time it is currently not well understood. Despite the fact that appropriately representing activity changes is essential for accurately capturing time course data from ion channels, systematic approaches for modelling modal gating are currently not available. In this paper, we develop a modular approach for building such a model in an iterative process. First, stochastic switching between modes and stochastic opening and closing within modes are represented in separate aggregated Markov models. Second, the continuous-time hierarchical Markov model, a new modelling framework proposed here, then enables us to combine these components so that in the integrated model both mode switching as well as the kinetics within modes are appropriately represented. A mathematical analysis reveals that the behaviour of the hierarchical Markov model naturally depends on the properties of its components. We also demonstrate how a hierarchical Markov model can be parametrized using experimental data and show that it provides a better representation than a previous model of the same dataset. Because evidence is increasing that modal gating reflects underlying molecular properties of the channel protein, it is likely that biophysical processes are better captured by our new approach than in earlier models.

scholarly journals A copula-based multivariate hidden Markov model for modelling momentum in football

2021 ◽  
Author(s):  
Marius Ötting ◽  
Roland Langrock ◽  
Antonello Maruotti
Keyword(s):  
Markov Model ◽  
Hidden Markov Models ◽  
Markov Models ◽  
Hidden Markov ◽  
State Dependence ◽  
Change Points ◽  
Sports Fans ◽  
Modelling Framework ◽  
State Dependent ◽  
Different Levels

AbstractWe investigate the potential occurrence of change points—commonly referred to as “momentum shifts”—in the dynamics of football matches. For that purpose, we model minute-by-minute in-game statistics of Bundesliga matches using hidden Markov models (HMMs). To allow for within-state dependence of the variables, we formulate multivariate state-dependent distributions using copulas. For the Bundesliga data considered, we find that the fitted HMMs comprise states which can be interpreted as a team showing different levels of control over a match. Our modelling framework enables inference related to causes of momentum shifts and team tactics, which is of much interest to managers, bookmakers, and sports fans.

scholarly journals IMPLEMENTASI CONTEXT AWARE PADA SISTEM TRAVEL PLANNER BERBASIS MOBILE

2021 ◽  
Vol 5 (1) ◽  
pp. 23-27
Author(s):  
Viery Darmawan ◽  
◽  
Rengga Asmara ◽  
Ira Prasetyaningrum
Keyword(s):  
Contextual Information ◽  
The Internet ◽  
Context Aware ◽  
New Approach ◽  
Tourist Attractions ◽  
Technological Advances ◽  
Long Time ◽  
Travel Efficiency ◽  
Opening And Closing

In the era of technological advances, tourists will first seek information about the tourist object to be addressed, even tourists often don't have a destination, so they have to search one by one via the internet. In determining travel plans, it is often to see one by one the review of tourist attractions and conclude the results will take a long time, while tourists need actual and fast information to determine the travel plans. In this study, the authors take a new approach, namely by creating a mobile-based travel planner system that compiles travel plans automatically by considering contextual information related to tourist location points, whether of tourist locations during travel days, travel opening and closing hours, so that it will increase travel efficiency without having to do the research manually which takes a long time. The system can also provide travel recommendations based on visitor comments sentiment on Google Places and is equipped with a trip route that will be generated automatically. This research is useful for helping tourists plan their trip actually because of the consideration of contextual information so that it will make it easier and save tourists time.

scholarly journals Mode Switching Is the Major Mechanism of Ligand Regulation of InsP3 Receptor Calcium Release Channels

2007 ◽  
Vol 130 (6) ◽  
pp. 631-645 ◽  
Author(s):  
Lucian Ionescu ◽  
Carl White ◽  
King-Ho Cheung ◽  
Jianwei Shuai ◽  
Ian Parker ◽  
...  
Keyword(s):  
Calcium Release ◽  
Critical Role ◽  
Cell Types ◽  
Mode Switching ◽  
Channel Activity ◽  
Open Probability ◽  
Major Mechanism ◽  
Modal Gating ◽  
Opening And Closing ◽  
Insp3 Receptor

The inositol 1,4,5-trisphosphate (InsP3) receptor (InsP3R) plays a critical role in generation of complex Ca2+ signals in many cell types. In patch clamp recordings of isolated nuclei from insect Sf9 cells, InsP3R channels were consistently detected with regulation by cytoplasmic InsP3 and free Ca2+ concentrations ([Ca2+]i) very similar to that observed for vertebrate InsP3R. Long channel activity durations of the Sf9-InsP3R have now enabled identification of a novel aspect of InsP3R gating: modal gating. Using a novel algorithm to analyze channel modal gating kinetics, InsP3R gating can be separated into three distinct modes: a low activity mode, a fast kinetic mode, and a burst mode with channel open probability (Po) within each mode of 0.007 ± 0.002, 0.24 ± 0.03, and 0.85 ± 0.02, respectively. Channels reside in each mode for long periods (tens of opening and closing events), and transitions between modes can be discerned with high resolution (within two channel opening and closing events). Remarkably, regulation of channel gating by [Ca2+]i and [InsP3] does not substantially alter channel Po within a mode. Instead, [Ca2+]i and [InsP3] affect overall channel Po primarily by changing the relative probability of the channel being in each mode, especially the high and low Po modes. This novel observation therefore reveals modal switching as the major mechanism of physiological regulation of InsP3R channel activity, with implications for the kinetics of Ca2+ release events in cells.

scholarly journals Statistical analysis of modal gating in ion channels

2014 ◽  
Vol 470 (2166) ◽  
pp. 20140030 ◽  
Author(s):  
Ivo Siekmann ◽  
James Sneyd ◽  
Edmund J. Crampin
Keyword(s):  
Ion Channels ◽  
Single Channel ◽  
Channel Activity ◽  
Experimental Conditions ◽  
Inositol Trisphosphate Receptor ◽  
Statistical Framework ◽  
Modal Gating ◽  
Opening And Closing ◽  
Trisphosphate Receptor ◽  
Different Levels

Ion channels regulate the concentrations of ions within cells. By stochastically opening and closing its pore, they enable or prevent ions from crossing the cell membrane. However, rather than opening with a constant probability, many ion channels switch between several different levels of activity even if the experimental conditions are unchanged. This phenomenon is known as modal gating: instead of directly adapting its activity, the channel seems to mix sojourns in active and inactive modes in order to exhibit intermediate open probabilities. Evidence is accumulating that modal gating rather than modulation of opening and closing at a faster time scale is the primary regulatory mechanism of ion channels. However, currently, no method is available for reliably calculating sojourns in different modes. In order to address this challenge, we develop a statistical framework for segmenting single-channel datasets into segments that are characteristic for particular modes. The algorithm finds the number of mode changes, detects their locations and infers the open probabilities of the modes. We apply our approach to data from the inositol-trisphosphate receptor. Based upon these results, we propose that mode changes originate from alternative conformational states of the channel protein that determine a certain level of channel activity.

Inter-country inequality as a dynamic process and the problem of post-industrial development

2018 ◽  
pp. 5-29 ◽  
Author(s):  
L. M. Grigoryev ◽  
V. A. Pavlyushina
Keyword(s):  
Economic Growth ◽  
Political Institutions ◽  
Industrial Development ◽  
Modern World ◽  
New Approach ◽  
Development Level ◽  
The World ◽  
Long Time ◽  
The Difference ◽  
Post Industrial

The phenomenon of economic growth is studied by economists and statisticians in various aspects for a long time. Economic theory is devoted to assessing factors of growth in the tradition of R. Solow, R. Barrow, W. Easterly and others. During the last quarter of the century, however, the institutionalists, namely D. North, D. Wallis, B. Weingast as well as D. Acemoglu and J. Robinson, have shown the complexity of the problem of development on the part of socioeconomic and political institutions. As a result, solving the problem of how economic growth affects inequality between countries has proved extremely difficult. The modern world is very diverse in terms of development level, and the article offers a new approach to the formation of the idea of stylized facts using cluster analysis. The existing statistics allows to estimate on a unified basis the level of GDP production by 174 countries of the world for 1992—2016. The article presents a structured picture of the world: the distribution of countries in seven clusters, different in levels of development. During the period under review, there was a strong per capita GDP growth in PPP in the middle of the distribution, poverty in various countries declined markedly. At the same time, in 1992—2016, the difference increased not only between rich and poor groups of countries, but also between clusters.

Improved Contrast in Ultra-Low-Field MRI with Time-Dependent Bipolar Prepolarizing Fields: Theory and NMR Demonstrations

2013 ◽  
Vol 20 (3) ◽  
pp. 327-336 ◽  
Author(s):  
Jaakko O. Nieminen ◽  
Jens Voigt ◽  
Stefan Hartwig ◽  
Hans Jürgen Scheer ◽  
Martin Burghoff ◽  
...  
Keyword(s):  
Field Strength ◽  
Time Course ◽  
Signal Strength ◽  
Relaxation Rates ◽  
Resonance Imaging ◽  
New Approach ◽  
Spin Lattice ◽  
Low Field ◽  
Low Field Mri ◽  
Magnetic Resonance Imaging Mri

Abstract The spin-lattice (T1) relaxation rates of materials depend on the strength of the external magnetic field in which the relaxation occurs. This T1 dispersion has been suggested to offer a means to discriminate between healthy and cancerous tissue by performing magnetic resonance imaging (MRI) at low magnetic fields. In prepolarized ultra-low-field (ULF) MRI, spin precession is detected in fields of the order of 10-100 μT. To increase the signal strength, the sample is first magnetized with a relatively strong polarizing field. Typically, the polarizing field is kept constant during the polarization period. However, in ULF MRI, the polarizing-field strength can be easily varied to produce a desired time course. This paper describes how a novel variation of the polarizing-field strength and duration can optimize the contrast between two types of tissue having different T1 relaxation dispersions. In addition, NMR experiments showing that the principle works in practice are presented. The described procedure may become a key component for a promising new approach of MRI at ultra-low fields

Acid-Sensing Ion Channels

2020 ◽  
Author(s):  
Stefan Gründer
Keyword(s):  
Nervous System ◽  
Ion Channels ◽  
Excitatory Synapses ◽  
Detailed Characterization ◽  
High Affinity ◽  
Acid Sensing Ion Channels ◽  
Long Time ◽  
Pathological Pain

Acid-sensing ion channels (ASICs) are proton-gated Na+ channels. Being almost ubiquitously present in neurons of the vertebrate nervous system, their precise function remained obscure for a long time. Various animal toxins that bind to ASICs with high affinity and specificity have been tremendously helpful in uncovering the role of ASICs. We now know that they contribute to synaptic transmission at excitatory synapses as well as to sensing metabolic acidosis and nociception. Moreover, detailed characterization of mouse models uncovered an unanticipated role of ASICs in disorders of the nervous system like stroke, multiple sclerosis, and pathological pain. This review provides an overview on the expression, structure, and pharmacology of ASICs plus a summary of what is known and what is still unknown about their physiological functions and their roles in diseases.

scholarly journals The long-term course of fatigue following breast cancer diagnosis

2020 ◽  
Vol 4 (1) ◽  
Author(s):  
Karin Biering ◽  
Morten Frydenberg ◽  
Helle Pappot ◽  
Niels Henrik Hjollund
Keyword(s):  
Breast Cancer ◽  
Time Course ◽  
Breast Cancer Diagnosis ◽  
Patient Characteristics ◽  
Repeated Measurements ◽  
Diagnosis And Treatment ◽  
Persistent Problem ◽  
Treatment Regimens ◽  
Long Time

Abstract Purpose Fatigue following breast cancer is a well-known problem, with both high and persistent prevalence. Previous studies suffer from lack of repeated measurements, late recruitment and short periods of follow-up. The course of fatigue from diagnosis and treatment to the long-time outcome status is unknown as well as differences in the level of fatigue between treatment regimens. The purpose of this study was to describe the long-time course of fatigue from the time of clinical suspicion of breast cancer, its dependence of patient characteristics and treatment regimens and the comparison with the course of fatigue among women with the same suspicion, but not diagnosed with breast cancer. Methods Three hundred thirty-two women referred to acute or subacute mammography was followed with questionnaires from before the mammography and up to 1500 days. Fatigue was measured by the Multidimensional Fatigue Inventory (MFI-20). The women reported their initial level of fatigue before the mammography and thus without knowledge of whether they had cancer or not. Both women with and without cancer were followed. Women with cancer were identified in the clinical database established by Danish Breast Cancer Cooperative Group (DBCG) to collect information on treatment regimen. Results Compared to fatigue scores before diagnosis, women with breast cancer reported a large increase of fatigue, especially in the first 6 months, followed by a slow decrease over time. Despite the long follow-up period, the women with breast cancer did not return to their level of fatigue at time of the mammography. Women without breast cancer, experienced a rapid decrease of fatigue after disproval of diagnosis followed by a steadier period. Conclusions Fatigue is a persistent problem in women diagnosed with breast cancer, even several years following diagnosis and treatment. The women with breast cancer were most affected by fatigue in the first 6 months after diagnosis.

Projecting demands for renal replacement therapy in the Northern Territory: a stochastic Markov model

2018 ◽  
Vol 42 (4) ◽  
pp. 380 ◽  
Author(s):  
Jiqiong You ◽  
Yuejen Zhao ◽  
Paul Lawton ◽  
Steven Guthridge ◽  
Stephen P. McDonald ◽  
...  
Keyword(s):  
Renal Replacement Therapy ◽  
Markov Model ◽  
Replacement Therapy ◽  
Management Practices ◽  
Markov Models ◽  
Self Care ◽  
Potential Effect ◽  
Northern Territory ◽  
Baseline Scenario ◽  
On Demand

Objective The aim of the present study was to evaluate the potential effects of different health intervention strategies on demand for renal replacement therapy (RRT) services in the Northern Territory (NT). Methods A Markov chain simulation model was developed to estimate demand for haemodialysis (HD) and kidney transplantation (Tx) over the next 10 years, based on RRT registry data between 2002 and 2013. Four policy-relevant scenarios were evaluated: (1) increased Tx; (2) increased self-care dialysis; (3) reduced incidence of end-stage kidney disease (ESKD); and (4) reduced mortality. Results There were 957 new cases of ESKD during the study period, with most patients being Indigenous people (85%). The median age was 50 years at onset and 57 years at death, 12 and 13 years younger respectively than Australian medians. The prevalence of RRT increased 5.6% annually, 20% higher than the national rate (4.7%). If current trends continue (baseline scenario), the demand for facility-based HD (FHD) would approach 100 000 treatments (95% confidence interval 75 000–121 000) in 2023, a 5% annual increase. Increasing Tx (0.3%), increasing self-care (5%) and reducing incidence (5%) each attenuate demand for FHD to ~70 000 annually by 2023. Conclusions The present study demonstrates the effects of changing service patterns to increase Tx, self-care and prevention, all of which will substantially attenuate the growth in FHD requirements in the NT. What is known about the topic? The burden of ESKD is projected to increase in the NT, with demand for FHD doubling every 15 years. Little is known about the potential effect of changes in health policy and clinical practice on demand. What does this paper add? This study assessed the usefulness of a stochastic Markov model to evaluate the effects of potential policy changes on FHD demand. What are the implications for practitioners? The scenarios simulated by the stochastic Markov models suggest that changes in current ESKD management practices would have a large effect on future demand for FHD.

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