Effects of 3D Geometries on Cellular Gradient Sensing and Polarization

During cell migration, cells become polarized, change their shape, and move in response to various internal and external cues. Cell polarization is defined through the spatio-temporal organization of molecules such as PI3K or small GTPases, and is determined by intracellular signaling networks. It results in directional forces through actin polymerization and myosin contractions. Many existing mathematical models of cell polarization are formulated in terms of reaction-diffusion systems of interacting molecules, and are often defined in one or two spatial dimensions. In this paper, we introduce a 3D reaction-diffusion model of interacting molecules in a single cell, and find that cell geometry has an important role affecting the capability of a cell to polarize, or change polarization when an external signal changes direction. Our results suggest a geometrical argument why more roundish cells can repolarize more effectively than cells which are elongated along the direction of the original stimulus, and thus enable roundish cells to turn faster, as has been observed in experiments. On the other hand, elongated cells preferentially polarize along their main axis even when a gradient stimulus appears from another direction. Furthermore, our 3D model can accurately capture the effect of binding and unbinding of important regulators of cell polarization to and from the cell membrane. This spatial separation of membrane and cytosol, not possible to capture in 1D or 2D models, leads to marked differences of our model from comparable lower-dimensional models.Comment: 31 pages, 7 figure

Models of education in medicine, public health, and engineering

Discussion on global health in both the academic and the public domain has focused largely on research, capacity building, and service delivery. Although these efforts along with financial commitments from public and private partners have contributed to a broader appreciation and understanding of global health challenges, the reflection of global health in academic training has largely been lacking. However, integrative models are beginning to appear

Solitary Wave-Series Solutions to Non-Linear Schrodinger Equations

ABSTRACT: In this paper, higher-order dispersive non-linear Schrodinger equations are studied. Their solitary wave-series solutions with continuity of the derivatives and specific discontinuity of the derivatives at the crest are presented. Furthermore, convergence of the series’ solutions is also validated and discussed with the help of graphs.  ABSTRAK: Kertas ini mengkaji persamaan Schrodinger serakan taklinear turutan tinggi. Penyelesaian siri-gelombang tunggalnya dengan kamiran berterusan dan kamiran tak berterusan pada maksimum telah dibentangkan. Penumpuan penyelesaian siri juga telah diperiksa dan dibincangkan dengan bantuan graf-graf. KEYWORDS: Schrodinger equation; solitary wave-series solution; continuity and discontinuity of derivatives at cres

Multiscale mechanobiology: computational models for integrating molecules to multicellular systems

Mechanical signals exist throughout the biological landscape. Across all scales, these signals, in the form of force, stiffness, and deformations, are generated and processed, resulting in an active mechanobiological circuit that controls many fundamental aspects of life, from protein unfolding and cytoskeletal remodeling to collective cell motions. The multiple scales and complex feedback involved present a challenge for fully understanding the nature of this circuit, particularly in development and disease in which it has been implicated. Computational models that accurately predict and are based on experimental data enable a means to integrate basic principles and explore fine details of mechanosensing and mechanotransduction in and across all levels of biological systems. Here we review recent advances in these models along with supporting and emerging experimental findings.National Cancer Institute (U.S.) (U01-CA177799

Biomedical Engineering Education and Practice Challenges and opportunities in improving health in developing countries

Abstract-While developed countries constantly pioneer new medical technologies, developing countries have been plighted with a lack of medical devices, resulting in poor health, poverty, and social inequality. Much of the medical equipment that these countries do have is broken, unusable due to a lack of electricity and infrastructure, or inappropriate for local needs. In 2000, the Global Forum for Health Research coined the term "10/90 Gap" to describe the fact that only 10% of health research funds are spent on the problems of 90% of the world's population. If the developing world is to acquire useful medical technologies, it must come from within, as the developed world has shown minimal interest in pursuing technologies for markets where the financial return is only nominal. If engineers in developed countries put their energy and resources into building the capacity of their counterparts in developing countries, they will be able to maximize their impact on the most relevant issues in global health. In order to succeed in their work abroad, biomedical engineers from developed countries must transition from being providers of solutions, to enablers of local innovation, thus contributing directly to both education and implementation. This paper addresses current challenges and appropriate solutions to tackle the lack of biomedical engineering education and innovation in developing countries

Controlling uncertainty in aptamer selection

The search for high-affinity aptamers for targets such as proteins, small molecules, or cancer cells remains a formidable endeavor. Systematic Evolution of Ligands by EXponential Enrichment (SELEX) offers an iterative process to discover these aptamers through evolutionary selection of high-affinity candidates from a highly diverse random pool. This randomness dictates an unknown population distribution of fitness parameters, encoded by the binding affinities, toward SELEX targets. Adding to this uncertainty, repeating SELEX under identical conditions may lead to variable outcomes. These uncertainties pose a challenge when tuning selection pressures to isolate high-affinity ligands. Here, we present a stochastic hybrid model that describes the evolutionary selection of aptamers to explore the impact of these unknowns. To our surprise, we find that even single copies of high-affinity ligands in a pool of billions can strongly influence population dynamics, yet their survival is highly dependent on chance. We perform Monte Carlo simulations to explore the impact of environmental parameters, such as the target concentration, on selection efficiency in SELEX and identify strategies to control these uncertainties to ultimately improve the outcome and speed of this time- and resource-intensive process.National Cancer Institute (U.S.) (5U01CA177799

Solid dissolution in a fluid solvent is characterized by the interplay of surface area-dependent diffusion and physical fragmentation

AbstractThe processes of dissolution and fragmentation have high relevance in pharmaceutical research, medicine, digestive physiology, and engineering design. Experimentally, dissolution and fragmentation are observed to occur simultaneously, yet little is known about the relative importance of each of these processes and their impact on the dissolution process as a whole. Thus, in order to better explain these phenomena and the manner in which they interact, we have developed a novel mathematical model of dissolution, based on partial differential equations, taking into consideration the two constituent processes of surface area-dependent diffusive mass removal and physical fragmentation of the solid particles, and the basic physical laws governing these processes. With this model, we have been able to quantify the effects of the interplay between these two processes and determine the optimal conditions for rapid solid dissolution in liquid solvents. We were able to reproduce experimentally observed phenomena and simulate dissolution under a wide range of experimentally occurring conditions to give new perspectives into the kinetics of this common, yet complex process. Finally, we demonstrated the utility of this model to aid in experiment and device design as an optimisation tool.</jats:p

Fluorescence dynamics of graphene quantum dots for detecting lard substance

Graphene Quantum Dots (GQD) is used for detecting lard substance. It is discovered that the fluorescence for a GQD with a size approximately 5nm in size will have a peak at 675nm. Introducing lard substance to the GQD will induce a broad fluorescence spectrum at the range of 415 till 715nm. Higher fluorescence is observed from 760nm till 860nm showing the dynamics fluorescence changes when lard is applied. These fluorescence dynamics when lard is introduced is due to the functional groups of Carbon-Carbon interaction between GQD and lard