Stem cell mechanobiology

Stem cells are undifferentiated cells that are capable of proliferation, self-maintenance and differentiation towards specific cell phenotypes. These processes are controlled by a variety of cues including physicochemical factors associated with the specific mechanical environment in which the cells reside. The control of stem cell biology through mechanical factors remains poorly understood and is the focus of the developing field of mechanobiology. This review provides an insight into the current knowledge of the role of mechanical forces in the induction of differentiation of stem cells. While the details associated with individual studies are complex and typically associated with the stem cell type studied and model system adopted, certain key themes emerge. First, the differentiation process affects the mechanical properties of the cells and of specific subcellular components. Secondly, that stem cells are able to detect and respond to alterations in the stiffness of their surrounding microenvironment via induction of lineage-specific differentiation. Finally, the application of external mechanical forces to stem cells, transduced through a variety of mechanisms, can initiate and drive differentiation processes. The coalescence of these three key concepts permit the introduction of a new theory for the maintenance of stem cells and alternatively their differentiation via the concept of a stem cell 'mechano-niche', defined as a specific combination of cell mechanical properties, extracellular matrix stiffness and external mechanical cues conducive to the maintenance of the stem cell population.<br/

The use of trade secrets to protect data shared between firms in agricultural and food sectors

Both public policy and business management are increasingly interested in how to manage trade secrets. One of the driving forces is the growing significance of data as an asset, as ‘oil of the 21st century'. Trade secrets are often seen as the major Intellectual Property (IP) tool for protecting data. There is also the understanding that the need to share data is increasing to allow for new types of innovation. This paper seeks to understand how data sharing practices and the use of trade secrets are evolving in the agricultural industries. Using explorative empirical data from four in-depth case studies, the paper develops a framework for data sharing practices, value sharing, and trade secrets use. We find that current data sharing practices pool around two scenarios, where data is not shared or shared only with limited partners (hence closed) and there are differences whether value created from the data is shared. We conclude that a nuanced view on the use of trade secrets in data sharing is mandated for both IP/data managers and scholars analysing the topic

Connected component identification and cluster update on GPU

Cluster identification tasks occur in a multitude of contexts in physics and engineering such as, for instance, cluster algorithms for simulating spin models, percolation simulations, segmentation problems in image processing, or network analysis. While it has been shown that graphics processing units (GPUs) can result in speedups of two to three orders of magnitude as compared to serial codes on CPUs for the case of local and thus naturally parallelized problems such as single-spin flip update simulations of spin models, the situation is considerably more complicated for the non-local problem of cluster or connected component identification. I discuss the suitability of different approaches of parallelization of cluster labeling and cluster update algorithms for calculations on GPU and compare to the performance of serial implementations.Comment: 15 pages, 14 figures, one table, submitted to PR

A fast algorithm for the multiple genome rearrangement problem with weighted reversals and transpositions

<p>Abstract</p> <p>Background</p> <p>Due to recent progress in genome sequencing, more and more data for phylogenetic reconstruction based on rearrangement distances between genomes become available. However, this phylogenetic reconstruction is a very challenging task. For the most simple distance measures (the breakpoint distance and the reversal distance), the problem is NP-hard even if one considers only three genomes.</p> <p>Results</p> <p>In this paper, we present a new heuristic algorithm that directly constructs a phylogenetic tree w.r.t. the weighted reversal and transposition distance. Experimental results on previously published datasets show that constructing phylogenetic trees in this way results in better trees than constructing the trees w.r.t. the reversal distance, and recalculating the weight of the trees with the weighted reversal and transposition distance. An implementation of the algorithm can be obtained from the authors.</p> <p>Conclusion</p> <p>The possibility of creating phylogenetic trees directly w.r.t. the weighted reversal and transposition distance results in biologically more realistic scenarios. Our algorithm can solve today's most challenging biological datasets in a reasonable amount of time.</p

Feasibility of a prehabilitation program before major abdominal surgery: a pilot prospective study.

To assess the feasibility of a prehabilitation program and its effects on physical performance and outcomes after major abdominal surgery. In this prospective pilot study, patients underwent prehabilitation involving three training sessions per week for 3 weeks preoperatively. The feasibility of delivering the intervention was assessed based on recruitment and adherence to the program. Its impacts on fitness (oxygen uptake (VO &lt;sub&gt;2&lt;/sub&gt; )) and physical performance (Timed Up and Go Test, 6-Minute Walk Test) were evaluated. From May 2017 to January 2020, 980 patients were identified and 44 (4.5%) were invited to participate. The main obstacles to patient recruitment were insufficient time (&lt;3 weeks) prior to scheduled surgery (n = 276, 28%) and screening failure (n = 312, 32%). Of the 44 patients, 24 (55%) declined to participate, and 20 (23%) were included. Of these, six (30%) were not adherent to the program. Among the remaining 14 patients, VO &lt;sub&gt;2&lt;/sub&gt; at ventilatory threshold significantly increased from 9.7 to 10.9 mL/min/kg. No significant difference in physical performance was observed before and after prehabilitation. Although prehabilitation seemed to have positive effects on exercise capacity, logistic and patient-related difficulties were encountered. The program is not feasible in its current form for all-comers

Isometric group actions on Banach spaces and representations vanishing at infinity

Our main result is that the simple Lie group $G=Sp(n,1)$ acts properly isometrically on $L^p(G)$ if $p>4n+2$. To prove this, we introduce property ({\BP}_0^V), for $V$ be a Banach space: a locally compact group $G$ has property ({\BP}_0^V) if every affine isometric action of $G$ on $V$, such that the linear part is a $C_0$-representation of $G$, either has a fixed point or is metrically proper. We prove that solvable groups, connected Lie groups, and linear algebraic groups over a local field of characteristic zero, have property ({\BP}_0^V). As a consequence for unitary representations, we characterize those groups in the latter classes for which the first cohomology with respect to the left regular representation on $L^2(G)$ is non-zero; and we characterize uniform lattices in those groups for which the first $L^2$-Betti number is non-zero.Comment: 28 page

Oxidative protein folding in bacteria

Ten years ago it was thought that disulphide bond formation in prokaryotes occurred spontaneously. Now two pathways involved in disulphide bond formation have been well characterized, the oxidative pathway, which is responsible for the formation of disulphides, and the isomerization pathway, which shuffles incorrectly formed disulphides. Disulphide bonds are donated directly to unfolded polypeptides by the DsbA protein; DsbA is reoxidized by DsbB. DsbB generates disulphides de novo from oxidized quinones. These quinones are reoxidized by the electron transport chain, showing that disulphide bond formation is actually driven by electron transport. Disulphide isomerization requires that incorrect disulphides be attacked using a reduced catalyst, followed by the redonation of the disulphide, allowing alternative disulphide pairing. Two isomerases exist in Escherichia coli , DsbC and DsbG. The membrane protein DsbD maintains these disulphide isomerases in their reduced and thereby active form. DsbD is kept reduced by cytosolic thioredoxin in an NADPH-dependent reaction.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75150/1/j.1365-2958.2002.02851.x.pd

The 1.2 A resolution crystal structure of TcpG, the Vibrio cholerae DsbA disulfide-forming protein required for pilus and cholera-toxin production

The enzyme TcpG is a periplasmic protein produced by the Gram-negative pathogen Vibrio cholerae. TcpG is essential for the production of ToxR-regulated proteins, including virulence-factor pilus proteins and cholera toxin, and is therefore a target for the development of a new class of anti-virulence drugs. Here, the 1.2 Å resolution crystal structure of TcpG is reported using a cryocooled crystal. This structure is compared with a previous crystal structure determined at 2.1 Å resolution from data measured at room temperature. The new crystal structure is the first DsbA crystal structure to be solved at a sufficiently high resolution to allow the inclusion of refined H atoms in the model. The redox properties of TcpG are also reported, allowing comparison of its oxidoreductase activity with those of other DSB proteins. One of the defining features of the Escherichia coli DsbA enzyme is its destabilizing disulfide, and this is also present in TcpG. The data presented here provide new insights into the structure and redox properties of this enzyme, showing that the binding mode identified between E. coli DsbB and DsbA is likely to be conserved in TcpG and that the [beta]5-[alpha]7 loop near the proposed DsbB binding site is flexible, and suggesting that the tense oxidized conformation of TcpG may be the consequence of a short contact at the active site that is induced by disulfide formation and is relieved by reduction

Multi-component Transparent Conducting Oxides: Progress in Materials Modelling

Transparent conducting oxides (TCOs) play an essential role in modern optoelectronic devices through their combination of electrical conductivity and optical transparency. We review recent progress in our understanding of multi-component TCOs formed from solid-solutions of ZnO, In2O3, Ga2O3 and Al2O3, with a particular emphasis on the contributions of materials modelling, primarily based on Density Functional Theory. In particular, we highlight three major results from our work: (i) the fundamental principles governing the crystal structures of multi-component oxide structures including (In2O3)(ZnO)n, named IZO, and (In2O3)m(Ga2O3)l(ZnO)n, named IGZO; (ii) the relationship between elemental composition and optical and electrical behaviour, including valence band alignments; (iii) the high-performance of amorphous oxide semiconductors. From these advances, the challenge of the rational design of novel electroceramic materials is discussed.Comment: Part of a themed issue of Journal of Physics: Condensed Matter on "Semiconducting Oxides". In Press (2011

Structural and Electronic Properties of Small Neutral (MgO)n Clusters

Ab initio Perturbed Ion (PI) calculations are reported for neutral stoichiometric (MgO)n clusters (n<14). An extensive number of isomer structures was identified and studied. For the isomers of (MgO)n (n<8) clusters, a full geometrical relaxation was considered. Correlation corrections were included for all cluster sizes using the Coulomb-Hartree-Fock (CHF) model proposed by Clementi. The results obtained compare favorably to the experimental data and other previous theoretical studies. Inclusion of correlaiotn is crucial in order to achieve a good description of these systems. We find an important number of new isomers which allows us to interpret the experimental magic numbers without the assumption of structures based on (MgO)3 subunits. Finally, as an electronic property, the variations in the cluster ionization potential with the cluster size were studied and related to the structural isomer properties.Comment: 24 pages, LaTeX, 7 figures in GIF format. Accepted for publication in Phys. Rev.