The homeostatic ensemble for cells

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Free-energy-based framework for early forecasting of stem cell differentiation.

Commitment of stem cells to different lineages is inherently stochastic but regulated by a range of environmental bio/chemo/mechanical cues. Here, we develop an integrated stochastic modelling framework for predicting the differentiation of hMSCs in response to a range of environmental cues, including sizes of adhesive islands, stiffness of substrates and treatment with ROCK inhibitors in both growth and mixed media. The statistical framework analyses the fluctuations of cell morphologies over approximately a 24 h period after seeding the cells in the specific environment and uses the cytoskeletal free-energy distribution to forecast the lineage the hMSCs will commit to. The cytoskeletal free energy which succinctly parametrizes the biochemical state of the cell is shown to capture hMSC commitment over a range of environments while simple morphological factors such as cell shape, tractions on their own are unable to correlate with lineages hMSCs adopt

Interfacial diffusion in high-temperature deformation of composites: A discrete dislocation plasticity investigation

© 2016 Elsevier Ltd We present a discrete dislocation plasticity (DDP) framework to analyse the high temperature deformation of multi-phase materials (composites) comprising a matrix and inclusions. Deformation of the phases is by climb-assisted glide of the dislocations while the particles can also deform due to stress-driven interfacial diffusion. The general framework is used to analyse the uniaxial tensile deformation of a composite comprising elastic particles with dislocation plasticity only present in the matrix phase. When dislocation motion is restricted to only glide within the matrix a strong size effect of the composite strength is predicted with the strength increasing with decreasing unit cell size due to dislocations forming pile-ups against the matrix/particle interface. Interfacial diffusion decreases the composite strength as it enhances the elongation of the elastic particles along the loading direction. When dislocation motion occurs by climb-assisted glide within the matrix the size effect of the strength is reduced as dislocations no longer arrange high energy pile-up structures but rather form lower energy dislocation cell networks. While interfacial diffusion again reduces the composite strength, in contrast to continuum plasticity predictions, the elongation of the particles is almost independent of the interfacial diffusion constant. Rather, in DDP the reduction in composite strength due to interfacial diffusion is a result of changes in the dislocation structures within the matrix and the associated enhanced dislocation climb rates in the matrix.Support from ONR under grant number N62909-14-1N242 on Multi-scale methods for creep resistant alloys (program manager Dr. David Shifler) is gratefully acknowledged

MicroMotility: State of the art, recent accomplishments and perspectives on the mathematical modeling of bio-motility at microscopic scales

Mathematical modeling and quantitative study of biological motility (in particular, of motility at microscopic scales) is producing new biophysical insight and is offering opportunities for new discoveries at the level of both fundamental science and technology. These range from the explanation of how complex behavior at the level of a single organism emerges from body architecture, to the understanding of collective phenomena in groups of organisms and tissues, and of how these forms of swarm intelligence can be controlled and harnessed in engineering applications, to the elucidation of processes of fundamental biological relevance at the cellular and sub-cellular level. In this paper, some of the most exciting new developments in the fields of locomotion of unicellular organisms, of soft adhesive locomotion across scales, of the study of pore translocation properties of knotted DNA, of the development of synthetic active solid sheets, of the mechanics of the unjamming transition in dense cell collectives, of the mechanics of cell sheet folding in volvocalean algae, and of the self-propulsion of topological defects in active matter are discussed. For each of these topics, we provide a brief state of the art, an example of recent achievements, and some directions for future research

Research trends in combinatorial optimization

Acknowledgments This work has been partially funded by the Spanish Ministry of Science, Innovation, and Universities through the project COGDRIVE (DPI2017-86915-C3-3-R). In this context, we would also like to thank the Karlsruhe Institute of Technology. Open access funding enabled and organized by Projekt DEAL.Peer reviewedPublisher PD

Free-energy-based framework for early forecasting of stem cell differentiation.

Commitment of stem cells to different lineages is inherently stochastic but regulated by a range of environmental bio/chemo/mechanical cues. Here, we develop an integrated stochastic modelling framework for predicting the differentiation of hMSCs in response to a range of environmental cues, including sizes of adhesive islands, stiffness of substrates and treatment with ROCK inhibitors in both growth and mixed media. The statistical framework analyses the fluctuations of cell morphologies over approximately a 24 h period after seeding the cells in the specific environment and uses the cytoskeletal free-energy distribution to forecast the lineage the hMSCs will commit to. The cytoskeletal free energy which succinctly parametrizes the biochemical state of the cell is shown to capture hMSC commitment over a range of environments while simple morphological factors such as cell shape, tractions on their own are unable to correlate with lineages hMSCs adopt

Zapotrzebowanie na nowe urządzenie testowe do peletyzacji biomasy

As the bulk density of biomass material is low, some problems are encountered during storage, transport and usage of biomass. In order to overcome these problems, densification process is necessary to increase the bulk density of the biomass. Biomass characteristics are improved, the volumetric heating value of biomass is increased, transportation and storage costs of biomass are reduced and the combustion characteristics of biomass are improved by a biomass densification process. Nowadays, pelletizing machines are widely used in the course of biomass densification. During the pelletizing machine's operation, obtaining the high quality compressed biomass with high capacity and less energy consumption is closely related to the pelletizing machine’s design criteria. Therefore, it is necessary to investigate all parameters that affect the pelletizing machine performance. In a laboratory scale, biomass pelletizing and densification tests are carried out by means of simplified pelletizing apparatus. Unfortunately, the tests that are executed by means of these apparatus, because of their operation principle, can not completely illustrate the pelletizing process and the forces which occur during this process. As the current systems which are used to simulate the pelletizing process are not sufficient, in order to clarify, model and optimize the pelletizing process much more effectively and to obtain necessary reliable data for pelletizing machine design, development of a new apparatus is necessary. The requirement of developing a new biomass pelletizing test device and its design principles are explained in this study.Ponieważ gęstość nasypowa biomasy jest niska, pojawiają się problemy podczas przechowywania, transportu i użytkowania biomasy. W celu pokonania tych problemów należy zastosować proces zagęszczenia by zwiększyć gęstość nasypową biomasy. Charakterystyka biomasy ulega poprawie, zwiększa się objętościowa wartość opałowa biomasy, koszty jej przechowania zostają zmniejszone a charakterystyka spalania biomasy poprawia się dzięki procesowi zagęszczenia. Obecnie, peleciarki mają szerokie zastosowanie w zagęszczaniu biomasy. Podczas pracy maszyny peletującej, osiągnięcie wysokiej jakości sprasowanej biomasy przy wysokiej wydajności i niskim zużyciu energii jest ściśle związane z kryteriami projektowania maszyny peletującej. Zatem, konieczne jest zbadanie parametrów, które wpływają na działanie maszyny peletującej. Na skale laboratoryjną, badania związane z peletyzacją i zagęszczaniem biomasy są prowadzone za pomocą uproszczonego aparatu peletyzującego. Niestety, badania, które prowadzone są za pomocą tej aparatury z powodu zasad jej działania nie mogą całkowicie zilustrować procesu peletyzacji i sił występujących podczas tego procesu. Ponieważ obecne systemy wykorzystywane w procesie peletyzcaji są niewystarczające, by wyjaśnić, wymodelować i zoptymizować proces peletyzacji w sposób bardziej skuteczny oraz by osiągnąć wiarygodne dane dla projektu maszyny peletującej, konieczne jest stworzenie nowej aparatury. Niniejsza praca wyjaśnia potrzebę stworzenia nowego urządzenia testowego do peletowania biomasy

Modelowanie zmiennego kąta nachylenia stoku w projektowaniu kopalni odkrywkowych za pomocą interpolacji funkcjami sklejającymi (metodą spline’ów)

In this paper a new method of modeling variable slope angles has been presented based on the spline interpolation method. Slope angle modeling and defining precedency of the blocks are the vital parts of almost any open pit optimization algorithm. Traditionally heuristic patterns such as 1:5 or 1:9 have been used to generate slope angles. Cone template based models were later employed in developing variable slope angles. They normally use a linear interpolation process for determination of slope angles between the given directions which leads to sharp and non-realistic pits. The other elliptical alternatives suffer from having limitations in defining slope angles in non-geographical directions. The method is capable to consider any number of slope angles in any desired direction as well as creating quite accurate and realistic pit shapes. Three major types of the spline interpolation including cubic, quadratic and cardinal are tested, however, the cubic form is preferred due to more realistic outcomes. Main steps of the method are described through a numerical case study.W pracy zaprezentowano nową metodę modelowania zmiennego kąta nachylenia gruntu w oparciu o metodę interpolacji funkcjami sklejającymi (metoda spline’ów). Modelowanie kąta nachylenia stoku i prognozowanie kolejności wybierania to kluczowe elementy algorytmu optymalizacyjnego. Tradycyjne modele heurystyczne oparte o wzorce 1:5 lub 1:9 wykorzystane zostały do wygenerowania kątów nachylenia stoku. Do wygenerowania zmiennych kątów nachylenia wykorzystano modele stożkowe. Procedura taka zasadniczo zakłada wykorzystanie interpolacji liniowej dla określenia kąta nachylenia pomiędzy dwoma kierunkami, co prowadzić może do zaprojektowania bardzo stromych i nierealistycznych kształtów odkrywek. Alternatywne rozwiązania, wykorzystujące modele eliptyczne, mają inne ograniczenia - mianowicie określają one kąty nachylenia w kierunkach innych niż geograficzne. Za pomocą tej metody uwzględnić można dowolną liczbę kątów nachylenia w dowolnym kierunku a także wygenerować dokładne i realistyczne kształty odkrywek. Przetestowano trzy procedury interpolacyjne: z zastosowaniem funkcji sześciennych, kwadratowych i kardynalnych. Zdecydowanie najkorzystniejsze i najbardziej realistyczne wyniki uzyskuje się przy zastosowaniu funkcji sześciennych. Główne etapy stosowanej metody wyjaśnione zostały przy pomocy przykładu numerycznego

Response of cells on a dense array of micro-posts

Abstract: We have analysed the response of cells on a bed of micro-posts idealized as a Winkler foundation using a homeostatic mechanics framework. The framework enables quantitative estimates of the stochastic response of cells along with the coupled analysis of cell spreading, contractility and mechano-sensitivity. In particular the model is shown to accurately predict that: (i) the extent of cell spreading, actin polymerisation as well as the traction forces that cells exert increase with increasing stiffness of the foundation; (ii) the traction forces that cells exert are primarily concentrated along the cell periphery; and (iii) while the total tractions increase with increasing cell area the average tractions are reasonably independent of cell area, i.e. for a given substrate stiffness, the average tractions that are normalized by cell area do not vary strongly with cell size. These results thus suggest that the increased foundation stiffness causes both the cell area and the average tractions that the cells exert to increase through higher levels of stress-fibre polymerization rather than the enhanced total tractions being directly linked through causation to the larger cell areas. A defining feature of the model is that its predictions are statistical in the form of probability distributions of observables such as the traction forces and cell area. In contrast, most existing models present solutions to specific boundary value problems where the cell morphology is imposed a priori. In particular, in line with observations we predict that the diversity of cell shapes, sizes and measured traction forces increase with increasing foundation stiffness. The homeostatic mechanics framework thus suggests that the diversity of observations in in vitro experiments is inherent to the homeostatic equilibrium of cells rather than being a result of experimental errors

A mechanism-based gradient damage model for metallic fracture

A new gradient-based formulation for predicting fracture in elastic-plastic solids is presented. Damage is captured by means of a phase field model that considers both the elastic and plastic works as driving forces for fracture. Material deformation is characterised by a mechanism-based strain gradient constitutive model. This non-local plastic-damage formulation is numerically implemented and used to simulate fracture in several paradigmatic boundary value problems. The case studies aim at shedding light into the role of the plastic and fracture length scales. It is found that the role of plastic strain gradients is two-fold. When dealing with sharp defects like cracks, plastic strain gradients elevate local stresses and facilitate fracture. However, in the presence of non-sharp defects failure is driven by the localisation of plastic flow, which is delayed due to the additional work hardening introduced by plastic strain gradients