Minimum information and guidelines for reporting a Multiplexed Assay of Variant Effect

Multiplexed Assays of Variant Effect (MAVEs) have emerged as a powerful approach for interrogating thousands of genetic variants in a single experiment. The flexibility and widespread adoption of these techniques across diverse disciplines has led to a heterogeneous mix of data formats and descriptions, which complicates the downstream use of the resulting datasets. To address these issues and promote reproducibility and reuse of MAVE data, we define a set of minimum information standards for MAVE data and metadata and outline a controlled vocabulary aligned with established biomedical ontologies for describing these experimental designs

Quantitative Modeling of Escherichia coli Chemotactic Motion in Environments Varying in Space and Time

Escherichia coli chemotactic motion in spatiotemporally varying environments is studied by using a computational model based on a coarse-grained description of the intracellular signaling pathway dynamics. We find that the cell's chemotaxis drift velocity vd is a constant in an exponential attractant concentration gradient [L]∝exp(Gx). vd depends linearly on the exponential gradient G before it saturates when G is larger than a critical value GC. We find that GC is determined by the intracellular adaptation rate kR with a simple scaling law: . The linear dependence of vd on G = d(ln[L])/dx directly demonstrates E. coli's ability in sensing the derivative of the logarithmic attractant concentration. The existence of the limiting gradient GC and its scaling with kR are explained by the underlying intracellular adaptation dynamics and the flagellar motor response characteristics. For individual cells, we find that the overall average run length in an exponential gradient is longer than that in a homogeneous environment, which is caused by the constant kinase activity shift (decrease). The forward runs (up the gradient) are longer than the backward runs, as expected; and depending on the exact gradient, the (shorter) backward runs can be comparable to runs in a spatially homogeneous environment, consistent with previous experiments. In (spatial) ligand gradients that also vary in time, the chemotaxis motion is damped as the frequency ω of the time-varying spatial gradient becomes faster than a critical value ωc, which is controlled by the cell's chemotaxis adaptation rate kR. Finally, our model, with no adjustable parameters, agrees quantitatively with the classical capillary assay experiments where the attractant concentration changes both in space and time. Our model can thus be used to study E. coli chemotaxis behavior in arbitrary spatiotemporally varying environments. Further experiments are suggested to test some of the model predictions

How do MNC R&D laboratory roles affect employee international assignments?

Research and development (R&D) employees are important human resources for multinational corporations (MNCs) as they are the driving force behind the advancement of innovative ideas and products. International assignments of these employees can be a unique way to upgrade their expertise; allowing them to effectively recombine their unique human resources to progress existing knowledge and advance new ones. This study aims to investigate the effect of the roles of R&D laboratories in which these employees work on the international assignments they undertake. We categorise R&D laboratory roles into those of the support laboratory, the locally integrated laboratory and the internationally interdependent laboratory. Based on the theory of resource recombinations, we hypothesise that R&D employees in support laboratories are not likely to assume international assignments, whereas those in locally integrated and internationally interdependent laboratories are likely to assume international assignments. The empirical evidence, which draws from research conducted on 559 professionals in 66 MNC subsidiaries based in Greece, provides support to our hypotheses. The resource recombinations theory that extends the resource based view can effectively illuminate the international assignment field. Also, research may provide more emphasis on the close work context of R&D scientists rather than analyse their demographic characteristics, the latter being the focus of scholarly practice hitherto

Dependence of Bacterial Chemotaxis on Gradient Shape and Adaptation Rate

Simulation of cellular behavior on multiple scales requires models that are sufficiently detailed to capture central intracellular processes but at the same time enable the simulation of entire cell populations in a computationally cheap way. In this paper we present RapidCell, a hybrid model of chemotactic Escherichia coli that combines the Monod-Wyman-Changeux signal processing by mixed chemoreceptor clusters, the adaptation dynamics described by ordinary differential equations, and a detailed model of cell tumbling. Our model dramatically reduces computational costs and allows the highly efficient simulation of E. coli chemotaxis. We use the model to investigate chemotaxis in different gradients, and suggest a new, constant-activity type of gradient to systematically study chemotactic behavior of virtual bacteria. Using the unique properties of this gradient, we show that optimal chemotaxis is observed in a narrow range of CheA kinase activity, where concentration of the response regulator CheY-P falls into the operating range of flagellar motors. Our simulations also confirm that the CheB phosphorylation feedback improves chemotactic efficiency by shifting the average CheY-P concentration to fit the motor operating range. Our results suggest that in liquid media the variability in adaptation times among cells may be evolutionary favorable to ensure coexistence of subpopulations that will be optimally tactic in different gradients. However, in a porous medium (agar) such variability appears to be less important, because agar structure poses mainly negative selection against subpopulations with low levels of adaptation enzymes. RapidCell is available from the authors upon request

Vector cavity solitons in broad area Vertical-Cavity Surface-Emitting lasers

We report the experimental observation of two-dimensional vector cavity solitons in a Vertical-Cavity Surface-Emitting Laser (VCSEL) under linearly polarized optical injection when varying optical injection linear polarization direction. The polarization of the cavity soliton is not the one of the optical injection as it acquires a distinct ellipticity. These experimental results are qualitatively reproduced by the spin-flip VCSEL model. Our findings open the road to polarization multiplexing when using cavity solitons in broad-area lasers as pixels in information technology

A generic travelling wave solution in dissipative laser cavity

A large family of cosh-Gaussian travelling wave solution of a complex Ginzburg–Landau equation (CGLE), that describes dissipative semiconductor laser cavity is derived. Using perturbation method, the stability region is identified. Bifurcation analysis is done by smoothly varying the cavity loss coefficient to provide insight of the system dynamics. He’s variational method is adopted to obtain the standard sech-type and the notso-explored but promising cosh-Gaussian type, travelling wave solutions. For a given set of system parameters, only one sech solution is obtained, whereas several distinct solution points are derived for cosh-Gaussian case. These solutions yield a wide variety of travelling wave profiles, namely Gaussian, near-sech, flat-top and a cosh-Gaussianwith variable central dip. A split-step Fourier method and pseudospectral method have been used for direct numerical solution of the CGLE and travelling wave profiles identical to the analytical profiles have been obtained. We also identified the parametric zone that promises an extremely large family of cosh-Gaussian travelling wave solutions with tunable shape. This suggests that the cosh-Gaussian profile is quite generic and would be helpful for further theoretical as well as experimental investigation on pattern formation, pulse dynamics andlocalization in semiconductor laser cavity

Ultra-porous titanium oxide scaffold with high compressive strength

Highly porous and well interconnected titanium dioxide (TiO2) scaffolds with compressive strength above 2.5 MPa were fabricated without compromising the desired pore architectural characteristics, such as high porosity, appropriate pore size, surface-to-volume ratio, and interconnectivity. Processing parameters and pore architectural characteristics were investigated in order to identify the key processing steps and morphological properties that contributed to the enhanced strength of the scaffolds. Cleaning of the TiO2 raw powder removed phosphates but introduced sodium into the powder, which was suggested to decrease the slurry stability. Strong correlation was found between compressive strength and both replication times and solid content in the ceramic slurry. Increase in the solid content resulted in more favourable sponge loading, which was achieved due to the more suitable rheological properties of the ceramic slurry. Repeated replication process induced only negligible changes in the pore architectural parameters indicating a reduced flaw size in the scaffold struts. The fabricated TiO2 scaffolds show great promise as load-bearing bone scaffolds for applications where moderate mechanical support is required

The Relationship Between Therapist Effects and Therapy Delivery Factors: Therapy Modality, Dosage, and Non-completion.

To consider the relationships between, therapist variability, therapy modality, therapeutic dose and therapy ending type and assess their effects on the variability of patient outcomes. Multilevel modeling was used to analyse a large sample of routinely collected data. Model residuals identified more and less effective therapists, controlling for case-mix. After controlling for case mix, 5.8 % of the variance in outcome was due to therapists. More sessions generally improved outcomes, by about half a point on the PHQ-9 for each additional session, while non-completion of therapy reduced the amount of pre-post change by six points. Therapy modality had little effect on outcome. Patient and service outcomes may be improved by greater focus on the variability between therapists and in keeping patients in therapy to completion

arrayMap: A Reference Resource for Genomic Copy Number Imbalances in Human Malignancies

Background: The delineation of genomic copy number abnormalities (CNAs) from cancer samples has been instrumental for identification of tumor suppressor genes and oncogenes and proven useful for clinical marker detection. An increasing number of projects have mapped CNAs using high-resolution microarray based techniques. So far, no single resource does provide a global collection of readily accessible oncoge- nomic array data. Methodology/Principal Findings: We here present arrayMap, a curated reference database and bioinformatics resource targeting copy number profiling data in human cancer. The arrayMap database provides a platform for meta-analysis and systems level data integration of high-resolution oncogenomic CNA data. To date, the resource incorporates more than 40,000 arrays in 224 cancer types extracted from several resources, including the NCBI's Gene Expression Omnibus (GEO), EBIs ArrayExpress (AE), The Cancer Genome Atlas (TCGA), publication supplements and direct submissions. For the majority of the included datasets, probe level and integrated visualization facilitate gene level and genome wide data re- view. Results from multi-case selections can be connected to downstream data analysis and visualization tools. Conclusions/Significance: To our knowledge, currently no data source provides an extensive collection of high resolution oncogenomic CNA data which readily could be used for genomic feature mining, across a representative range of cancer entities. arrayMap represents our effort for providing a long term platform for oncogenomic CNA data independent of specific platform considerations or specific project dependence. The online database can be accessed at http://www.arraymap.org.Comment: 17 pages, 5 inline figures, 3 tables, supplementary figures/tables split into 4 PDF files; manuscript submitted to PLoS ON