War, peace and Parliament: experts respond to the government’s defeat on Syrian intervention

The government’s defeat in the House of Commons on the issue of military intervention represents a constitutional landmark. Although Parliament still lacks any formal war powers, the Prime Minister has pledged to abide by MPs’ decision. In this post, Democratic Audit asks leading parliamentary and constitutional experts for their views on the implications of the vote

Detection of divergent genes in microbial aCGH experiments

BACKGROUND: Array-based comparative genome hybridization (aCGH) is a tool for rapid comparison of genomes from different bacterial strains. The purpose of such analysis is to detect highly divergent or absent genes in a sample strain compared to an index strain. Development of methods for analyzing aCGH data has primarily focused on copy number abberations in cancer research. In microbial aCGH analyses, genes are typically ranked by log-ratios, and classification into divergent or present is done by choosing a cutoff log-ratio, either manually or by statistics calculated from the log-ratio distribution. As experimental settings vary considerably, it is not possible to develop a classical discriminant or statistical learning approach. METHODS: We introduce a more efficient method for analyzing microbial aCGH data using a finite mixture model and a data rotation scheme. Using the average posterior probabilities from the model fitted to log-ratios before and after rotation, we get a score for each gene, and demonstrate its advantages for ranking and detecting divergent genes with enlarged specificity and sensitivity. RESULTS: The procedure is tested and compared to other approaches on simulated data sets, as well as on four experimental validation data sets for aCGH analysis on fully sequenced strains of Staphylococcus aureus and Streptococcus pneumoniae. CONCLUSION: When tested on simulated data as well as on four different experimental validation data sets from experiments with only fully sequenced strains, our procedure out-competes the standard procedures of using a simple log-ratio cutoff for classification into present and divergent genes

Improved Arithmetic Performance by Combining Stateful and Non‐Stateful Logic in Resistive Random Access Memory 1T–1R Crossbars

Computing-in-memory (CIM) is a promising approach for overcoming the memory-wall problem in conventional von-Neumann architectures. This is done by performing certain computation tasks directly in the storage subsystem without transferring data between storage and processing units. Stateful and non-stateful CIM concepts are recently attracting lots of interest, which are demonstrated as logical complete, energy efficient, and compatible with dense crossbar structures. However, sneak-path currents in passive resistive random access memory (RRAM) crossbars degrade the operation reliability and require the usage of active 1 Transistor–1 Resistance (1T-1R) bitcell designs. In this article, the arithmetic performance and reliability are investigated based on experimental measurements and variability-aware circuit simulations. Herein, it is aimed for the evaluation of logic operations specifically with fully integrated 1T–1R crossbar devices. Based on these operations, an N-bit full adder with optimized energy consumption and latency is demonstrated by combining stateful and non-stateful CIM logic styles with regard to the specific conditions in active 1T–1R RRAM crossbars

Activated fibronectin-secretory phenotype of mesenchymal stromal cells in pre-fibrotic myeloproliferative neoplasms

We characterized bone marrow stromal cells (BMSC) from patients with pre-fibrotic myeloproliferative neoplasms (MPN). MPN-BMSC showed decreased capacity to stimulate the proliferation of colony-forming units of normal hematopoietic stem and progenitor cells and displayed increased matrix remodelling (in particular fibronectin deposition) compared to control BMSC. This finding was confirmed in pre-fibrotic MPN bone marrow biopsies in a tissue microarray (n = 34), which stained positive for fibronectin in the absence of reticulin as a standard myelofibrosis marker. Fibronectin expression correlated significantly with reduced haemoglobin levels in MPN-patients (p = 0.007; R2 = 0.42). Our data show significant cell-intrinsic alterations in MPN-MSC and suggest that Fibronectin expression might be applicable as a biomarker for the identification of early myelofibrotic transformation in reticulin-negative MPN

Mandipropamid as a chemical inducer of proximity for in vivo applications

Direct control of protein interactions by chemically induced protein proximity holds great potential for both cell and synthetic biology as well as therapeutic applications. Low toxicity, orthogonality and excellent cell permeability are important criteria for chemical inducers of proximity (CIPs), in particular for in vivo applications. Here, we present the use of the agrochemical mandipropamid (Mandi) as a highly efficient CIP in cell culture systems and living organisms. Mandi specifically induces complex formation between a sixfold mutant of the plant hormone receptor pyrabactin resistance 1 (PYR1) and abscisic acid insensitive (ABI). It is orthogonal to other plant hormone-based CIPs and rapamycin-based CIP systems. We demonstrate the applicability of the Mandi system for rapid and efficient protein translocation in mammalian cells and zebrafish embryos, protein network shuttling and manipulation of endogenous proteins