Cell mechanics in flow: algorithms and applications

The computer simulations are pervasively used to improve the knowledge about biophysical phenomena and to quantify effects which are difficult to study experimentally. Generally, the numerical methods and models are desired to be as accurate as possible on the chosen length and time scales, but, at the same time, affordable in terms of computations. Until recently, the cell mechanics and blood flow phenomena on the sub-micron resolution could not be rigorously studied using computer simulations. However, within the last decade, advances in methods and hardware catalyzed the development of models for cells mechanics and blood flow modeling which, previously, were considered to be not feasible. In this context, a model should accurately describe a phenomenon, be computationally affordable, and be flexible to be applied to study different biophysical changes. This thesis focuses on the development of the new methods, models, and high-performance software implementation that expand the class of problems which can be studied numerically using particle-based methods. Microvascular networks have complex geometry, often without any symmetry, and to study them we need to tackle computational domains with several inlets and outlets. However, an absence of appropriate boundary conditions for particle- based methods hampers study of the blood flow in these domains. Another obstacle to model complex blood flow problems is the absence the highperformance software. This problem restricts the applicability of the of particlebased cell flow models to relatively small systems. Although there are several validated red blood cell models, to date, there are no models for suspended eukaryotic cells. The present thesis addresses these issues. We introduce new open boundary conditions for particle-based systems and apply them to study blood flow in a part of a microvascular network. We develop a software demonstrating outstanding performance on the largest supercomputers and used it to study blood flow in microfluidic devices. Finally, we present a new eukaryotic cell model which helps in quantifying the effect of sub-cellular components on the cell mechanics during deformations in microfluidic devices

Forecast of key indicators of retail network in time

The purpose of the study is to forecast the commodity demand, within which key indicators related to the operation of the retail network are applied. The relevance of the study is determined by the need to forecast the indicators significant for retail trade development to increase the planning efficiency of trade organization activity. The importance to forecast the future values of the indicators under consideration – the temperature regime and the number of checks – has been indicated. These indicators are significant for adequate forecasting of demand and for solving other management tasks as well. The range of the analysis methods of time series has been determined. These series have been used to solve the tasks of forecasting demand for the retail network. The approach of the state-space model is considered in almost every method. The theoretical basis of each method has been described to illuminate a sufficient variety of the applied mathematical tools. The fact that conventional (ARIMA, exponential smoothing) and modern methods used by large IT companies (Facebook and Google) are among the applied methods of forecasting has been emphasized. The choice of the prediction quality metric for the problem has been justified. The metrics are a square root of the root-mean-square error and the absolute error in percentage. A set of daily data about the amount of checks in the retail network of Izhevsk, as well as the average daily temperature conditions in the geographical area of the city have been used as the input data to make the forecast. To make short-term forecasts, the initial sample is suggested to be divided into a training sample and a test one in the proportion 9 to 1, due to the short-term of the forecast. The importance of the temperature series indicator for the activity of a retail store and for the dynamics of consumer demand has been characterized. The issue to forecast temperature accurately only on the basis of temperature time series has been discussed in the study. The models for temperature series have been calculated and the quality indicators for each model have been estimated. The value of the indicator of the number of checks to demonstrate the activity of retail trade has been described. A number of external factors affecting the dynamics of the number of checks have been listed in the present research. Among them are days of the week, whether it is a pre-holiday or a holiday. We have made conclusions about the high efficiency of the composite forecast with several methods on the basis of the predictive modeling of the check amount. Even with the help of the arithmetic mean of the forecasts for several methods, it is possible to create a more accurate prediction than for each method separately. Our further research will concern the improvement of the tool and the development of a computer-based system to forecast commodity demand

A microfabricated deformability-based flow cytometer with application to malaria

Malaria resulting from Plasmodium falciparum infection is a major cause of human suffering and mortality. Red blood cell (RBC) deformability plays a major role in the pathogenesis of malaria. Here we introduce an automated microfabricated “deformability cytometer” that measures dynamic mechanical responses of 10[superscript 3] to 10[superscript 4] individual RBCs in a cell population. Fluorescence measurements of each RBC are simultaneously acquired, resulting in a population-based correlation between biochemical properties, such as cell surface markers, and dynamic mechanical deformability. This device is especially applicable to heterogeneous cell populations. We demonstrate its ability to mechanically characterize a small number of P. falciparum-infected (ring stage) RBCs in a large population of uninfected RBCs. Furthermore, we are able to infer quantitative mechanical properties of individual RBCs from the observed dynamic behavior through a dissipative particle dynamics (DPD) model. These methods collectively provide a systematic approach to characterize the biomechanical properties of cells in a high-throughput manner.National Institutes of Health (U.S.) (Grant R01 HL094270-01A1)National Institutes of Health (U.S.) (Grant 1-R01-GM076689-01)Singapore-MIT Alliance for Research and Technology Cente

Coupled coarse graining and Markov Chain Monte Carlo for lattice systems

We propose an efficient Markov Chain Monte Carlo method for sampling equilibrium distributions for stochastic lattice models, capable of handling correctly long and short-range particle interactions. The proposed method is a Metropolis-type algorithm with the proposal probability transition matrix based on the coarse-grained approximating measures introduced in a series of works of M. Katsoulakis, A. Majda, D. Vlachos and P. Plechac, L. Rey-Bellet and D.Tsagkarogiannis,. We prove that the proposed algorithm reduces the computational cost due to energy differences and has comparable mixing properties with the classical microscopic Metropolis algorithm, controlled by the level of coarsening and reconstruction procedure. The properties and effectiveness of the algorithm are demonstrated with an exactly solvable example of a one dimensional Ising-type model, comparing efficiency of the single spin-flip Metropolis dynamics and the proposed coupled Metropolis algorithm.Comment: 20 pages, 4 figure

Precision of surfaces machined on a lathe with geometric errors

© 2017, Allerton Press, Inc.The precision attained in the shape and mutual position of cylindrical surfaces after machining may be assessed by means of a mathematical model. The effectiveness of the model is confirmed in practice

Trochoidal slot milling

© 2017, Allerton Press, Inc. Parameter specification in the trochoidal machining of a slot of constant width is considered. A formula is proposed for the displacement increment of the shaping circle as a function of the cutting depth

Errors in shaping by a planetary mechanism

© 2017, Allerton Press, Inc. The proposed planetary reaming method permits discontinuous turning in which the cutting edge moves relative to the cutting surfaces. As a result, individual sections of the cutting zone move successfully in and out of the machining zone. Discontinuous turning is free of the deficiencies of continuous turning

Derivation of flow related risk indices for stenosed left anterior descending coronary arteries with the use of computer simulations

The geometry of the coronary vessel network is believed to play a decisive role in the initiation, progression and outcome of coronary artery disease (CAD) and the occurrence of acute coronary syndromes (ACS). It also determines the flow field in the coronary artery which can be linked to CAD evolution. In this work geometric 3D models of left anterior descending (LAD) coronary arteries associated with either myocardial infarction (MI) or stable (STA) CAD were constructed. Transient numerical simulations of the flow for each model showed that specific flow patterns develop in different extent in the different groups examined. Recirculation zones, present distal the stenosis in all models, had larger extent and duration in MI cases. For mild stenosis (up to 50%) areas with low time averaged wall shear stress TAWSS (3 Pa) appeared only in MI models; in moderate and severe stenosis (>50%) these areas were present in all models but were significantly larger for MI than STA models. These differentiations were expressed via numerical indices based on TAWSS, oscillating shear index (OSI) and relative residence time (RRT). Additionally we introduced the coagulation activation index (CAI), based on the threshold behaviour of coagulation initiation, which exceeded the suggested threshold only for MI models with intermediate stenosis (up to 50%). These results show that numerical simulations of flow can produce arithmetic indices linked with the risk of CAD complications

Combined Simulation and Experimental Study of Large Deformation of Red Blood Cells in Microfluidic Systems

Author manuscript; available in PMC 2012 March 1.We investigate the biophysical characteristics of healthy human red blood cells (RBCs) traversing microfluidic channels with cross-sectional areas as small as 2.7 × 3 μm. We combine single RBC optical tweezers and flow experiments with corresponding simulations based on dissipative particle dynamics (DPD), and upon validation of the DPD model, predictive simulations and companion experiments are performed in order to quantify cell deformation and pressure–velocity relationships for different channel sizes and physiologically relevant temperatures. We discuss conditions associated with the shape transitions of RBCs along with the relative effects of membrane and cytosol viscosity, plasma environments, and geometry on flow through microfluidic systems at physiological temperatures. In particular, we identify a cross-sectional area threshold below which the RBC membrane properties begin to dominate its flow behavior at room temperature; at physiological temperatures this effect is less profound.Singapore-MIT Alliance for Research and TechnologyUnited States. National Institutes of Health (National Heart, Lung, and Blood Institute Award R01HL094270

Multi-omics reveal the lifestyle of the acidophilic, mineral-oxidizing model species Leptospirillum ferriphilum(T).

Leptospirillum ferriphilum plays a major role in acidic, metal rich environments where it represents one of the most prevalent iron oxidizers. These milieus include acid rock and mine drainage as well as biomining operations. Despite its perceived importance, no complete genome sequence of this model species' type strain is available, limiting the possibilities to investigate the strategies and adaptations Leptospirillum ferriphilum(T) applies to survive and compete in its niche. This study presents a complete, circular genome of Leptospirillum ferriphilum(T) DSM 14647 obtained by PacBio SMRT long read sequencing for use as a high quality reference. Analysis of the functionally annotated genome, mRNA transcripts, and protein concentrations revealed a previously undiscovered nitrogenase cluster for atmospheric nitrogen fixation and elucidated metabolic systems taking part in energy conservation, carbon fixation, pH homeostasis, heavy metal tolerance, oxidative stress response, chemotaxis and motility, quorum sensing, and biofilm formation. Additionally, mRNA transcript counts and protein concentrations were compared between cells grown in continuous culture using ferrous iron as substrate and bioleaching cultures containing chalcopyrite (CuFeS2). Leptospirillum ferriphilum(T) adaptations to growth on chalcopyrite included a possibly enhanced production of reducing power, reduced carbon dioxide fixation, as well as elevated RNA transcripts and proteins involved in heavy metal resistance, with special emphasis on copper efflux systems. Finally, expression and translation of genes responsible for chemotaxis and motility were enhanced.IMPORTANCELeptospirillum ferriphilum is one of the most important iron-oxidizers in the context of acidic and metal rich environments during moderately thermophilic biomining. A high-quality circular genome of Leptospirillum ferriphilum(T) coupled with functional omics data provides new insights into its metabolic properties, such as the novel identification of genes for atmospheric nitrogen fixation, and represents an essential step for further accurate proteomic and transcriptomic investigation of this acidophile model species in the future. Additionally, light is shed on Leptospirillum ferriphilum(T) adaptation strategies to growth on the copper mineral chalcopyrite. This data can be applied to deepen our understanding and optimization of bioleaching and biooxidation, techniques that present sustainable and environmentally friendly alternatives to many traditional methods for metal extraction