119 research outputs found
Enhanced force-field calibration via machine learning
The influence of microscopic force fields on the motion of Brownian particles plays a fundamental role in a broad range of fields, including soft matter, biophysics, and active matter. Often, the experimental calibration of these force fields relies on the analysis of the trajectories of the Brownian particles. However, such an analysis is not always straightforward, especially if the underlying force fields are non-conservative or time-varying, driving the system out of thermodynamic equilibrium. Here, we introduce a toolbox to calibrate microscopic force fields by analyzing the trajectories of a Brownian particle using machine learning, namely, recurrent neural networks. We demonstrate that this machine-learning approach outperforms standard methods when characterizing the force fields generated by harmonic potentials if the available data are limited. More importantly, it provides a tool to calibrate force fields in situations for which there are no standard methods, such as non-conservative and time-varying force fields. In order to make this method readily available for other users, we provide a Python software package named DeepCalib, which can be easily personalized and optimized for specific force fields and applications. This package is ideal to calibrate complex and non-standard force fields from short trajectories, for which advanced specific methods would need to be developed on a case-by-case basis
Relationships and events: towards a general theory of reification and truthmaking.
We propose a novel ontological analysis of relations and relationships based on a re-visitation of a classic problem in the practice of knowledge repre- sentation and conceptual modeling, namely relationship reification. Our idea is that a relation holds in virtue of a relationship's existence. Relationships are therefore truthmakers of relations. In this paper we present a general theory or reification and truthmaking, and discuss the interplay between events and rela- tionships, suggesting that relationships are the focus of events, which emerge from the context (the scene) they occur in
Brain health: time matters in multiple sclerosis
publisher: Elsevier articletitle: Brain health: time matters in multiple sclerosis journaltitle: Multiple Sclerosis and Related Disorders articlelink: http://dx.doi.org/10.1016/j.msard.2016.07.003 content_type: article copyright: © 2016 Oxford PharmaGenesis Ltd. Published by Elsevier B.V
Lipidation of Pneumococcal Antigens Leads to Improved Immunogenicity and Protection
Streptococcus pneumoniaeinfections lead to high morbidity and mortality rates worldwide.Pneumococcal polysaccharide conjugate vaccines significantly reduce the burden of disease but havea limited range of protection, which encourages the development of a broadly protective protein-basedalternative. We and others have shown that immunization with pneumococcal lipoproteins that lackthe lipid anchor protects against colonization. Since immunity againstS. pneumoniaeis mediatedthrough Toll-like receptor 2 signaling induced by lipidated proteins, we investigated the effects ofa lipid modification on the induced immune responses in either intranasally or subcutaneouslyvaccinated mice. Here, we demonstrate that lipidation of recombinant lipoproteins DacB and PnrAstrongly improves their immunogenicity. Mice immunized with lipidated proteins showed enhancedantibody concentrations and different induction kinetics. The induced humoral immune responsewas modulated by lipidation, indicated by increased IgG2/IgG1 subclass ratios related to Th1-typeimmunity. In a mouse model of colonization, immunization with lipidated antigens led to a moderatebut consistent reduction of pneumococcal colonization as compared to the non-lipidated proteins,indicating that protein lipidation can improve the protective capacity of the coupled antigen. Thus,protein lipidation represents a promising approach for the development of a serotype-independentpneumococcal vaccine
Testing the differential adhesion hypothesis across the epithelial− mesenchymal transition
Weanalyze the mechanical properties of three epithelial/mesenchymal cell lines (MCF-10A, MDAMB-
231, MDA-MB-436) that exhibit a shift in E-, N- and P-cadherin levels characteristic of an
epithelial−mesenchymal transition associated with processes such as metastasis, to quantify the role of
cell cohesion in cell sorting and compartmentalization. Wedevelop a unique set of methods to
measure cell–cell adhesiveness, cell stiffness and cell shapes, and compare the results to predictions
from cell sorting in mixtures of cell populations.Wefind that the final sorted state is extremely robust
among all three cell lines independent of epithelial or mesenchymal state, suggesting that cell sorting
may play an important role in organization and boundary formation in tumours.Wefind that surface
densities of adhesive molecules do not correlate with measured cell–cell adhesion, but do correlate
with cell shapes, cell stiffness and the rate at which cells sort, in accordance with an extended version of
the differential adhesion hypothesis (DAH). Surprisingly, theDAHdoes not correctly predict the final
sorted state. This suggests that these tissues are not behaving as immiscible fluids, and that dynamical
effects such as directional motility, friction and jamming may play an important role in tissue
compartmentalization across the epithelial−mesenchymal transition
FMNL formins boost lamellipodial force generation
Migration frequently involves Rac-mediated protrusion of lamellipodia, formed by Arp2/3 complex-dependent branching thought to be crucial for force generation and stability of these networks. The formins FMNL2 and FMNL3 are Cdc42 effectors targeting to the lamellipodium tip and shown here to nucleate and elongate actin filaments with complementary activities in vitro. In migrating B16-F1 melanoma cells, both formins contribute to the velocity of lamellipodium protrusion. Loss of FMNL2/3 function in melanoma cells and fibroblasts reduces lamellipodial width, actin filament density and -bundling, without changing patterns of Arp2/3 complex incorporation. Strikingly, in melanoma cells, FMNL2/3 gene inactivation almost completely abolishes protrusion forces exerted by lamellipodia and modifies their ultrastructural organization. Consistently, CRISPR/Cas-mediated depletion of FMNL2/3 in fibroblasts reduces both migration and capability of cells to move against viscous media. Together, we conclude that force generation in lamellipodia strongly depends on FMNL formin activity, operating in addition to Arp2/3 complex-dependent filament branching
Theories in Business and Information Systems Engineering
Even though the idea of science enjoys an impressive reputation, there seems to be no precise conception of science. On the one hand, there is no unified definition of the extension of activities subsumed under the notion of science. According to the narrow conception that is common in Anglo-Saxon countries, science is restricted to those disciplines that investigate nature and aim at explanation and prediction of natural phenomena. A wider conception that can be found in various European countries includes social sciences, the humanities and engineering. On the other hand and related to the first aspect, there is still no general consensus on the specific characteristics of scientific discoveries and scientific knowledge
Meta Modeling for Business Process Improvement
Conducting business process improvement (BPI) initiatives is a topic of high priority for today’s companies. However, performing BPI projects has become challenging. This is due to rapidly changing customer requirements and an increase of inter-organizational business processes, which need to be considered from an end-to-end perspective. In addition, traditional BPI approaches are more and more perceived as overly complex and too resource-consuming in practice. Against this background, the paper proposes a BPI roadmap, which is an approach for systematically performing BPI projects and serves practitioners’ needs for manageable BPI methods. Based on this BPI roadmap, a domain-specific conceptual modeling method (DSMM) has been developed. The DSMM supports the efficient documentation and communication of the results that emerge during the application of the roadmap. Thus, conceptual modeling acts as a means for purposefully codifying the outcomes of a BPI project. Furthermore, a corresponding software prototype has been implemented using a meta modeling platform to assess the technical feasibility of the approach. Finally, the usability of the prototype has been empirically evaluated
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