Cooperative contractility: the role of stress fibres in the regulation of cell-cell junctions.

We present simulations of cell-cell adhesion as reported in a recent study [Liu et al., 2010, PNAS, 107(22), 9944-9] for two cells seeded on an array of micro-posts. The micro-post array allows for the measurement of forces exerted by the cell and these show that the cell-cell tugging stress is a constant and independent of the cell-cell junction area. In the current study, we demonstrate that a material model which includes the underlying cellular processes of stress fibre contractility and adhesion formation can capture these results. The simulations explain the experimentally observed phenomena whereby the cell-cell junction forces increase with junction size but the tractions exerted by the cell on the micro-post array are independent of the junction size. Further simulations on different types of micro-post arrays and cell phenotypes are presented as a guide to future experiments.WR and PMcG acknowledge Science Foundation Ireland grant 10/RFP/ENM2960 and Short Term Travel Fellowship (STTF 11).This is the accepted manuscript. The final version is available from Elsevier at http://www.sciencedirect.com/science/article/pii/S0021929014006137

pZMO7-Derived shuttle vectors for heterologous protein expression and proteomic applications in the ethanol-producing bacterium Zymomonas mobilis

Background The ethanol-producing bacterium Zymomonas mobilis has attracted considerable scientific and commercial interest due to its exceptional physiological properties. Shuttle vectors derived from native plasmids have previously been successfully used for heterologous gene expression in this bacterium for a variety of purposes, most notably for metabolic engineering applications. Results A quantitative PCR (qPCR) approach was used to determine the copy numbers of two endogenous double stranded DNA plasmids: pZMO1A (1,647 bp) and pZMO7 (pZA1003; 4,551 bp) within the NCIMB 11163 strain of Z. mobilis. Data indicated pZMO1A and pZMO7 were present at ca. 3-5 and ca. 1-2 copies per cell, respectively. A ca. 1,900 bp fragment from plasmid pZMO7 was used to construct two Escherichia coli - Z. mobilis shuttle vectors (pZ7C and pZ7-184). The intracellular stabilities and copy numbers of pZ7C and pZ7-184 were characterized within the NCIMB 11163, ATCC 29191 and (ATCC 10988-derived) CU1 Rif2 strains of Z. mobilis. Both shuttle vectors could be stably maintained within the ATCC 29191 strain (ca. 20-40 copies per cell), and the CU1 Rif2 strain (ca. 2-3 copies per cell), for more than 50 generations in the absence of an antibiotic selectable marker. A selectable marker was required for shuttle vector maintenance in the parental NCIMB 11163 strain; most probably due to competition for replication with the endogenous pZMO7 plasmid molecules. N-terminal glutathione S-transferase (GST)-fusions of four endogenous proteins, namely the acyl-carrier protein (AcpP); 2-dehydro-3-deoxyphosphooctonate aldolase (KdsA); DNA polymerase III chi subunit (HolC); and the RNA chaperone protein Hfq; were successfully expressed from pZ7C-derived shuttle vectors, and their protein-protein binding interactions were analyzed in Z. mobilis ATCC 29191. Using this approach, proteins that co-purified with AcpP and KdsA were identified. Conclusions We show that a shuttle vector-based protein affinity 'pull-down' approach can be used to probe protein interaction networks in Z. mobilis cells. Our results demonstrate that protein expression plasmids derived from pZMO7 have significant potential for use in future biological or biotechnological applications within Z. mobilis.published_or_final_versio

Prevention of poxvirus infection by tetrapyrroles

BACKGROUND: Prevention of poxvirus infection is a topic of great current interest. We report inhibition of vaccinia virus in cell culture by porphyrins and phthalocyanines. Most previous work on the inhibition of viruses with tetrapyrroles has involved photodynamic mechanisms. The current study, however, investigates light-independent inhibition activity. METHODS: The Western Reserve (WR) and International Health Department-J (IHD-J) strains of vaccinia virus were used. Virucidal and antiviral activities as well as the cytotoxicity of test compounds were determined. RESULTS: Examples of active compounds include zinc protoporphyrin, copper hematoporphyrin, meso(2,6-dihydroxyphenyl)porphyrin, the sulfonated tetra-1-naphthyl and tetra-1-anthracenylporphyrins, selected sulfonated derivatives of halogenated tetraphenyl porphyrins and the copper chelate of tetrasulfonated phthalocyanine. EC(50 )values for the most active compounds are as low as 0.05 µg/mL (40 nM). One of the most active compounds was the neutral meso(2,6-dihydroxyphenyl)porphyrin, indicating that the compounds do not have to be negatively charged to be active. CONCLUSIONS: Porphyrins and phthalocyanines have been found to be potent inhibitors of infection by vaccinia virus in cell culture. These tetrapyrroles were found to be active against two different virus strains, and against both enveloped and non-enveloped forms of the virus, indicating that these compounds may be broadly effective in their ability to inhibit poxvirus infection

Timed Implementation Relations for the Distributed Test Architecture

In order to test systems that have physically distributed interfaces, called ports, we might use a distributed approach in which there is a separate tester at each port. If the testers do not synchronise during testing then we cannot always determine the relative order of events observed at different ports and this leads to new notions of correctness that have been described using corresponding implementation relations. We study the situation in which each tester has a local clock and timestamps its observations. If we know nothing about how the local clocks relate then this does not affect the implementation relation while if the local clocks agree exactly then we can reconstruct the sequence of observations made. In practice, however, we are likely to be between these extremes: the local clocks will not agree exactly but we have some information regarding how they can differ. We start by assuming that a local tester interacts synchronously with the corresponding port of the system under test and then extend this to the case where communications can be asynchronous, considering both the first-in-first-out (FIFO) case and the non-FIFO case. The new implementation relations are stronger than implementation relations for distributed testing that do not use timestamps but still reflect the distributed nature of observations. This paper explores these alternatives and derives corresponding implementation relations

Investigating Students' Experiences with Collaboration Analytics for Remote Group Meetings.

Remote meetings have become the norm for most students learning synchronously at a distance during the ongoing coronavirus pandemic. This has motivated the use of artificial intelligence in education (AIED) solutions to support the teaching and learning practice in these settings. However, the use of such solutions requires new research particularly with regards to the human factors that ultimately shape the future design and implementations. In this paper, we build on the emerging literature on human-centred AIED and explore students’ experiences after interacting with a tool that monitors their collaboration in remote meetings (i.e., using Zoom) during 10 weeks. Using the social translucence framework, we probed into the feedback provided by twenty students regarding the design and implementation requirements of the system after their exposure to the tool in their course. The results revealed valuable insights in terms of visibility (what should be made visible to students via the system), awareness (how can this information increase students’ understanding of collaboration performance), and accountability (to what extent students take responsibility of changing their behaviours based on the system’s feedback); as well as the ethical and privacy aspects related to the use of collaboration analytics tools in remote meetings. This study provides key suggestions for the future design and implementations of AIED systems for remote meetings in educational settings

Balanced electric-magnetic dihole in Kaluza-Klein theory

We present a four-dimensional double-black-hole (or dihole) solution in Kaluza-Klein theory, describing a superposition of an electrically charged and a magnetically charged black hole. This system can be balanced for appropriately chosen parameters, and the resulting space-time is completely regular on and outside the event horizons. This solution was constructed using the inverse-scattering method in five-dimensional vacuum gravity, in which it describes a rotating black ring surrounding a static black hole on a Taub-NUT background space. Various properties of this solution are studied, from both a four- and five-dimensional perspective.Comment: 33 pages, 6 figures; v2: expanded discussion of phase space, published versio

Sign-reversal of the in-plane resistivity anisotropy in hole-doped iron pnictides

The in-plane anisotropy of the electrical resistivity across the coupled orthorhombic and magnetic transitions of the iron pnictides has been extensively studied in the parent and electron-doped compounds. All these studies universally show that the resistivity $\rho_{a}$ across the long orthorhombic axis $a_{O}$ - along which the spins couple antiferromagnetically below the magnetic transition temperature - is smaller than the resistivity $\rho_{b}$ of the short orthorhombic axis $b_{O}$, i. e. $\rho_{a}<\rho_{b}$. Here we report that in the hole-doped compounds Ba$_{1-x}$K$_{x}$Fe$_{2}$As$_{2}$, as the doping level increases, the resistivity anisotropy initially becomes vanishingly small, and eventually changes sign for sufficiently large doping, i. e. $\rho_{b}<\rho_{a}$. This observation is in agreement with a recent theoretical prediction that considers the anisotropic scattering of electrons by spin-fluctuations in the orthorhombic/nematic state.Comment: This paper has been replaced by the new version offering new explanation of the experimental results first reported her

Integrated multiple mediation analysis: A robustness–specificity trade-off in causal structure

Recent methodological developments in causal mediation analysis have addressed several issues regarding multiple mediators. However, these developed methods differ in their definitions of causal parameters, assumptions for identification, and interpretations of causal effects, making it unclear which method ought to be selected when investigating a given causal effect. Thus, in this study, we construct an integrated framework, which unifies all existing methodologies, as a standard for mediation analysis with multiple mediators. To clarify the relationship between existing methods, we propose four strategies for effect decomposition: two-way, partially forward, partially backward, and complete decompositions. This study reveals how the direct and indirect effects of each strategy are explicitly and correctly interpreted as path-specific effects under different causal mediation structures. In the integrated framework, we further verify the utility of the interventional analogues of direct and indirect effects, especially when natural direct and indirect effects cannot be identified or when cross-world exchangeability is invalid. Consequently, this study yields a robustness–specificity trade-off in the choice of strategies. Inverse probability weighting is considered for estimation. The four strategies are further applied to a simulation study for performance evaluation and for analyzing the Risk Evaluation of Viral Load Elevation and Associated Liver Disease/Cancer data set from Taiwan to investigate the causal effect of hepatitis C virus infection on mortality

Blow-up solutions for linear perturbations of the Yamabe equation

For a smooth, compact Riemannian manifold (M,g) of dimension N \geg 3, we are interested in the critical equation $$\Delta_g u+(N-2/4(N-1) S_g+\epsilon h)u=u^{N+2/N-2} in M, u>0 in M,$$ where \Delta_g is the Laplace--Beltrami operator, S_g is the Scalar curvature of (M,g), $h\in C^{0,\alpha}(M)$, and $\epsilon$ is a small parameter