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Mathematical modelling

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https://www.readbyqxmd.com/read/28641400/cytosolic-delivery-of-sirna-by-ultra-high-affinity-dsrna-binding-proteins
#1
Nicole J Yang, Monique J Kauke, Fangdi Sun, Lucy F Yang, Katie F Maass, Michael W Traxlmayr, Yao Yu, Yingda Xu, Robert S Langer, Daniel G Anderson, K Dane Wittrup
Protein-based methods of siRNA delivery are capable of uniquely specific targeting, but are limited by technical challenges such as low potency or poor biophysical properties. Here, we engineered a series of ultra-high affinity siRNA binders based on the viral protein p19 and developed them into siRNA carriers targeted to the epidermal growth factor receptor (EGFR). Combined in trans with a previously described endosome-disrupting agent composed of the pore-forming protein Perfringolysin O (PFO), potent silencing was achieved in vitro with no detectable cytotoxicity...
June 21, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28641269/a-model-based-tool-for-the-analysis-and-design-of-gene-regulatory-network
#2
Liliana Ironi, Ettore Lanzarone
Computational and mathematical models have significantly contributed to the rapid progress in the study of gene regulatory networks (GRN), but researchers still lack a reliable model-based framework for computer-aided analysis and design. Such tool should both reveal the relation between network structure and dynamics and find parameter values and/or constraints that enable the simulated dynamics to reproduce specific behaviors. This paper addresses these issues and proposes a computational framework that facilitates network analysis or design...
June 19, 2017: IEEE/ACM Transactions on Computational Biology and Bioinformatics
https://www.readbyqxmd.com/read/28641265/a-new-method-for-neural-spike-alignment-the-centroid-filter
#3
Benjamin Metcalfe, Chris Clarke, Nick Donaldson, John Taylor
Recordings made directly from the nervous system are a key tool in experimental electrophysiology and the development of bioelectronic medicines. Analysis of these recordings involves the identification of signals from individual neurons, a process known as spike sorting. A critical and limiting feature of spike sorting is the need to align individual spikes in time. However, electrophysiological recordings are made in extremely noisy environments that seriously limit the performance of the spike-alignment process...
June 16, 2017: IEEE Transactions on Neural Systems and Rehabilitation Engineering
https://www.readbyqxmd.com/read/28641256/a-novel-fast-tensor-based-preconditioner-for-image-restoration
#4
Mansoor Rezghi
Image restoration is one of the main parts of image processing. Mathematically, this problem can be modeled as a large scale structured ill-posed linear system. Ill-posedness of this problem results in low convergence rate of iterative solvers. For speeding up the convergence, preconditioning usually is used. Despite the existing preconditioners for image restoration which are constructed based on approximations of the blurring matrix, in this paper, we propose a novel preconditioner with a different viewpoint...
June 16, 2017: IEEE Transactions on Image Processing: a Publication of the IEEE Signal Processing Society
https://www.readbyqxmd.com/read/28640810/lassim-a-network-inference-toolbox-for-genome-wide-mechanistic-modeling
#5
Rasmus Magnusson, Guido Pio Mariotti, Mattias Köpsén, William Lövfors, Danuta R Gawel, Rebecka Jörnsten, Jörg Linde, Torbjörn Nordling, Elin Nyman, Sylvie Schulze, Colm E Nestor, Huan Zhang, Gunnar Cedersund, Mikael Benson, Andreas Tjärnberg, Mika Gustafsson
Recent technological advancements have made time-resolved, quantitative, multi-omics data available for many model systems, which could be integrated for systems pharmacokinetic use. Here, we present large-scale simulation modeling (LASSIM), which is a novel mathematical tool for performing large-scale inference using mechanistically defined ordinary differential equations (ODE) for gene regulatory networks (GRNs). LASSIM integrates structural knowledge about regulatory interactions and non-linear equations with multiple steady state and dynamic response expression datasets...
June 22, 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28636920/nanog-fluctuations-in-embryonic-stem-cells-highlight-the-problem-of-measurement-in-cell-biology
#6
Rosanna C G Smith, Patrick S Stumpf, Sonya J Ridden, Aaron Sim, Sarah Filippi, Heather A Harrington, Ben D MacArthur
A number of important pluripotency regulators, including the transcription factor Nanog, are observed to fluctuate stochastically in individual embryonic stem cells. By transiently priming cells for commitment to different lineages, these fluctuations are thought to be important to the maintenance of, and exit from, pluripotency. However, because temporal changes in intracellular protein abundances cannot be measured directly in live cells, fluctuations are typically assessed using genetically engineered reporter cell lines that produce a fluorescent signal as a proxy for protein expression...
June 20, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28636811/performance-evaluation-of-gpu-parallelization-space-time-adaptive-algorithms-and-their-combination-for-simulating-cardiac-electrophysiology
#7
Rafael S Oliveira, Bernardo M Rocha, Denise Burgarelli, Wagner Meira, Christakis Constantinides, Rodrigo Weber Dos Santos
The use of computer models as a tool for the study and understanding of the complex phenomena of cardiac electrophysiology has attained increased importance nowadays. At the same time, the increased complexity of the biophysical processes translates into complex computational and mathematical models. In order to speed up cardiac simulations and to allow more precise and realistic uses, two different techniques have been traditionally exploited: parallel computing and sophisticated numerical methods. In this work, we combine a modern parallel computing technique based on multicore and graphics processing units (GPUs), and a sophisticated numerical method based on a new space-time adaptive algorithm...
June 21, 2017: International Journal for Numerical Methods in Biomedical Engineering
https://www.readbyqxmd.com/read/28636047/decoding-the-regulatory-mechanism-of-glucose-and-insulin-induced-phosphatidylinositol-3-4-5-trisphosphate-dynamics-in-%C3%AE-cells
#8
Tagari Samanta, Peeyush Sharma, Dwijendra Kukri, Sandip Kar
In MIN6 pancreatic β-cells, glucose and insulin act in a synergistic manner to regulate the dynamics of Phosphatidylinositol (3,4,5)-trisphosphate (PIP3). However, the precise regulatory mechanism behind such an experimentally observed synergy is poorly understood. In this article, we propose a phenomenological mathematical model for studying the glucose and insulin driven PIP3 activation dynamics under various stimulatory conditions to unfold the mechanism responsible for the observed synergy. The modeling study reveals that the experimentally observed oscillation in PIP3 dynamics with disparate time scales for different external glucose doses is mainly orchestrated by the complex dynamic regulation of cytosolic Ca(2+) in β-cells...
June 21, 2017: Molecular BioSystems
https://www.readbyqxmd.com/read/28635569/stratification-model-based-on-early-postprostatectomy-prostate-specific-antigen-kinetics-may-help-to-reduce-the-risk-of-overtreatment-in-candidates-for-adjuvant-radiotherapy
#9
Stepan Vesely, Ladislav Jarolim, Marek Schmidt, Joana Do Carmo Silva, Katerina Duskova, Marko Babjuk
OBJECTIVE: The aim of this study was to construct a stratification model based on early postoperative kinetics of prostate-specific antigen (PSA) to select the most suitable high-risk patients for early intervention after radical prostatectomy (RP). MATERIALS AND METHODS: The study evaluated 205 men who had undergone RP without any adjuvant treatment. All of the patients had positive surgical margins, extracapsular extension and/or seminal vesicle invasion. The patients underwent multiple ultrasensitive PSA measurements on days 14, 30, 60 and 90 after RP, and subsequently at 3 month intervals...
February 24, 2017: Scandinavian Journal of Urology
https://www.readbyqxmd.com/read/28634857/computational-modelling-of-cancer-development-and-growth-modelling-at-multiple-scales-and-multiscale-modelling
#10
Zuzanna Szymańska, Maciej Cytowski, Elaine Mitchell, Cicely K Macnamara, Mark A J Chaplain
In this paper, we present two mathematical models related to different aspects and scales of cancer growth. The first model is a stochastic spatiotemporal model of both a synthetic gene regulatory network (the example of a three-gene repressilator is given) and an actual gene regulatory network, the NF-[Formula: see text]B pathway. The second model is a force-based individual-based model of the development of a solid avascular tumour with specific application to tumour cords, i.e. a mass of cancer cells growing around a central blood vessel...
June 20, 2017: Bulletin of Mathematical Biology
https://www.readbyqxmd.com/read/28634784/attentional-weights-in-vision-as-products-of-spatial-and-nonspatial-components
#11
Maria Nordfang, Camilla Staugaard, Claus Bundesen
The relationship between visual attentional selection of items in particular spatial locations and selection by nonspatial criteria was investigated in a partial report experiment with report of letters (as many as possible) from brief postmasked exposures of circular arrays of letters and digits. The data were fitted by mathematical models based on Bundesen's (Psychological Review, 97, 523-547, 1990) theory of visual attention (TVA). Both attentional weights of targets (letters) and attentional weights of distractors (digits) showed strong variations across the eight possible target locations, but for each of the ten participants, the ratio of the weight of a distractor at a given location to the weight of a target at the same location was approximately constant...
June 20, 2017: Psychonomic Bulletin & Review
https://www.readbyqxmd.com/read/28634351/a-dynamical-model-for-activating-and-silencing-the-mitotic-checkpoint
#12
Richard Henze, Peter Dittrich, Bashar Ibrahim
The spindle assembly checkpoint (SAC) is an evolutionarily conserved mechanism, exclusively sensitive to the states of kinetochores attached to microtubules. During metaphase, the anaphase-promoting complex/cyclosome (APC/C) is inhibited by the SAC but it rapidly switches to its active form following proper attachment of the final spindle. It had been thought that APC/C activity is an all-or-nothing response, but recent findings have demonstrated that it switches steadily. In this study, we develop a detailed mathematical model that considers all 92 human kinetochores and all major proteins involved in SAC activation and silencing...
June 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28634131/cost-effectiveness-of-pre-versus-post-liver-transplant-hepatitis-c-treatment-with-direct-acting-antivirals
#13
Sumeyye Samur, Brian Kues, Turgay Ayer, Mark S Roberts, Fasiha Kanwal, Chin Hur, Drew Michael S Donnell, Raymond T Chung, Jagpreet Chhatwal
BACKGROUND & AIMS: Oral direct-acting antivirals (DAAs) for hepatitis C virus (HCV) treatment offer new hope to both pre- and post-liver transplant (LT) patients. However, whether to treat HCV patients pre- versus post-LT is not clear, as treatment can improve liver function but could reduce the chance of receiving a LT while on the waiting list. Our objective was to evaluate the cost-effectiveness of pre-LT versus post-LT HCV treatment with oral DAAs in decompensated cirrhotic patients on the LT waiting list...
June 17, 2017: Clinical Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/28633990/cellular-gauge-symmetry-and-the-li-organization-principle-a-mathematical-addendum-quantifying-energetic-dynamics-in-physical-and-biological-systems-through-a-simple-geometric-tool-and-geodetic-curves
#14
REVIEW
Alexander Yurkin, Arturo Tozzi, James F Peters, Pedro C Marijuán
The present Addendum complements the accompanying paper "Cellular Gauge Symmetry and the Li Organization Principle"; it illustrates a recently-developed geometrical physical model able to assess electronic movements and energetic paths in atomic shells. The model describes a multi-level system of circular, wavy and zigzag paths which can be projected onto a horizontal tape. This model ushers in a visual interpretation of the distribution of atomic electrons' energy levels and the corresponding quantum numbers through rather simple tools, such as compasses, rulers and straightforward calculations...
June 17, 2017: Progress in Biophysics and Molecular Biology
https://www.readbyqxmd.com/read/28633306/multivariate-phylogenetic-comparative-methods-evaluations-comparisons-and-recommendations
#15
Dean C Adams, Michael L Collyer
Recent years have seen increased interest in phylogenetic comparative analyses of multivariate datasets, but to date the varied proposed approaches have not been extensively examined. Here we review the mathematical properties required of any multivariate method, and specifically evaluate existing multivariate phylogenetic comparative methods in this context. Phylogenetic comparative methods based on the full multivariate likelihood are robust to levels of covariation among trait dimensions and are insensitive to the orientation of the dataset, but display increasing model misspecification as the number of trait dimensions increases...
June 13, 2017: Systematic Biology
https://www.readbyqxmd.com/read/28632743/in-silico-assessment-of-the-effects-of-quinidine-disopyramide-and-e-4031-on-short-qt-syndrome-variant-1-in-the-human-ventricles
#16
Cunjin Luo, Kuanquan Wang, Henggui Zhang
AIMS: Short QT syndrome (SQTS) is an inherited disorder associated with abnormally abbreviated QT intervals and an increased incidence of atrial and ventricular arrhythmias. SQT1 variant (linked to the rapid delayed rectifier potassium channel current, IKr) of SQTS, results from an inactivation-attenuated, gain-of-function mutation (N588K) in the KCNH2-encoded potassium channels. Pro-arrhythmogenic effects of SQT1 have been well characterized, but less is known about the possible pharmacological antiarrhythmic treatment of SQT1...
2017: PloS One
https://www.readbyqxmd.com/read/28631947/predominant-contribution-of-l-type-cav1-2-channel-stimulation-to-impaired-intracellular-calcium-and-cerebral-artery-vasoconstriction-in-diabetic-hyperglycemia
#17
Stefano Morotti, Madeline Nieves-Cintrón, Matthew A Nystoriak, Manuel F Navedo, Eleonora Grandi
Enhanced L-type Ca(2+) channel (LTCC) activity in arterial myocytes contributes to vascular dysfunction during diabetes. Modulation of LTCC activity under hyperglycemic conditions could result from membrane potential-dependent and independent mechanisms. We have demonstrated that elevations in extracellular glucose (HG), similar to hyperglycemic conditions during diabetes, stimulate LTCC activity through phosphorylation of CaV1.2 at serine 1928. Prior studies have also shown that HG can suppress the activity of K(+) channels in arterial myocytes, which may contribute to vasoconstriction via membrane depolarization...
February 10, 2017: Channels
https://www.readbyqxmd.com/read/28631803/a-gompertz-model-approach-to-microbial-inactivation-kinetics-by-high-pressure-processing-hpp-model-selection-and-experimental-validation
#18
Vinicio Serment-Moreno, Claudio Fuentes, José Antonio Torres, Jorge Welti-Chanes
A recently proposed Gompertz model (GMPZ) approach describing microbial inactivation kinetics by high-pressure processing (HPP) incorporated the initial microbial load (N0 ) and lower microbial quantification limit (Nlim ), and simplified the dynamic effects of come-up time (CUT). The inactivation of Listeria innocua in milk by HPP treatments at 300, 400, 500, and 600 MPa and pressure holding times (thold ) ≤10 min was determined experimentally to validate this model approach. Models based on exponential, logistic-exponential, and inverse functions were evaluated to describe the effect of pressure on the lag time (λ) and maximum inactivation rate (μmax ), whereas the asymptote difference (A) was fixed as A = log10 (N0 /Nlim )...
June 20, 2017: Journal of Food Science
https://www.readbyqxmd.com/read/28630885/bayesian-framework-inspired-no-reference-region-of-interest-quality-measure-for-brain-mri-images
#19
Michael Osadebey, Marius Pedersen, Douglas Arnold, Katrina Wendel-Mitoraj
We describe a postacquisition, attribute-based quality assessment method for brain magnetic resonance imaging (MRI) images. It is based on the application of Bayes theory to the relationship between entropy and image quality attributes. The entropy feature image of a slice is segmented into low- and high-entropy regions. For each entropy region, there are three separate observations of contrast, standard deviation, and sharpness quality attributes. A quality index for a quality attribute is the posterior probability of an entropy region given any corresponding region in a feature image where quality attribute is observed...
April 2017: Journal of Medical Imaging
https://www.readbyqxmd.com/read/28630826/predicting-the-effects-of-interventions-a-tutorial-on-the-disequilibrium-model
#20
Kenneth W Jacobs, Zachary H Morford, James E King, Linda J Hayes
The disequilibrium approach to reinforcement and punishment, derived from the probability-differential hypothesis and response deprivation hypothesis, provides a number of potentially useful mathematical models for practitioners. The disequilibrium approach and its accompanying models have proven effective in the prediction and control of behavior, yet they have not been fully espoused and integrated into clinical practice. The purpose of this tutorial is to detail the disequilibrium approach and adapt its mathematical models for use as a tool in applied settings...
June 2017: Behavior Analysis in Practice
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