Protein O-Mannosylation in the Murine Brain: Occurrence of Mono-O-Mannosyl Glycans and Identification of New Substrates

Protein O-mannosylation is a post-translational modification essential for correct development of mammals. In humans, deficient O-mannosylation results in severe congenital muscular dystrophies often associated with impaired brain and eye development. Although various O-mannosylated proteins have been identified in the recent years, the distribution of O-mannosyl glycans in the mammalian brain and target proteins are still not well defined. In the present study, rabbit monoclonal antibodies directed against the O-mannosylated peptide YAT(α1-Man)AV were generated. Detailed characterization of clone RKU-1-3-5 revealed that this monoclonal antibody recognizes O-linked mannose also in different peptide and protein contexts. Using this tool, we observed that mono-O-mannosyl glycans occur ubiquitously throughout the murine brain but are especially enriched at inhibitory GABAergic neurons and at the perineural nets. Using a mass spectrometry-based approach, we further identified glycoproteins from the murine brain that bear single O-mannose residues. Among the candidates identified are members of the cadherin and plexin superfamilies and the perineural net protein neurocan. In addition, we identified neurexin 3, a cell adhesion protein involved in synaptic plasticity, and inter-alpha-trypsin inhibitor 5, a protease inhibitor important in stabilizing the extracellular matrix, as new O-mannosylated glycoproteins

Locating bugs without looking back

Bug localisation is a core program comprehension task in software maintenance: given the observation of a bug, e.g. via a bug report, where is it located in the source code? Information retrieval (IR) approaches see the bug report as the query, and the source code files as the documents to be retrieved, ranked by relevance. Such approaches have the advantage of not requiring expensive static or dynamic analysis of the code. However, current state-of-the-art IR approaches rely on project history, in particular previously fixed bugs or previous versions of the source code. We present a novel approach that directly scores each current file against the given report, thus not requiring past code and reports. The scoring method is based on heuristics identified through manual inspection of a small sample of bug reports. We compare our approach to eight others, using their own five metrics on their own six open source projects. Out of 30 performance indicators, we improve 27 and equal 2. Over the projects analysed, on average we find one or more affected files in the top 10 ranked files for 76% of the bug reports. These results show the applicability of our approach to software projects without history

Geometry-controlled kinetics

It has long been appreciated that transport properties can control reaction kinetics. This effect can be characterized by the time it takes a diffusing molecule to reach a target -- the first-passage time (FPT). Although essential to quantify the kinetics of reactions on all time scales, determining the FPT distribution was deemed so far intractable. Here, we calculate analytically this FPT distribution and show that transport processes as various as regular diffusion, anomalous diffusion, diffusion in disordered media and in fractals fall into the same universality classes. Beyond this theoretical aspect, this result changes the views on standard reaction kinetics. More precisely, we argue that geometry can become a key parameter so far ignored in this context, and introduce the concept of "geometry-controlled kinetics". These findings could help understand the crucial role of spatial organization of genes in transcription kinetics, and more generally the impact of geometry on diffusion-limited reactions.Comment: Submitted versio

On the Impact of Link Layer Retransmissions on TCP for Aeronautical Communications

In this article, we evaluate the impact of link layer retransmissions on the performance of TCP in the context of aeronautical communications.We present the architecture of aeronautical networks, which is manly driven by an important channel access delay, and the various retransmission strategies that can be implemented at both link and transport layers. We consider a worst case scenario to illustrate the benefits provided by the ARQ scheme at the link layer in terms of transmission delay.We evaluate the trade-off between allowing a fast data transmission and a low usage of satellite capacity by adjusting link layer parameters

Neuroimaging in Leber Hereditary Optic Neuropathy: State-of-the-art and future prospects

Leber Hereditary Optic Neuropathy (LHON) is an inherited mitochondrial retinal disease that causes the degeneration of retinal ganglion cells and leads to drastic loss of visual function. In the last decades, there has been a growing interest in using Magnetic Resonance Imaging (MRI) to better understand mechanisms of LHON beyond the retina. This is partially due to the emergence of gene-therapies for retinal diseases, and the accompanying expanded need for reliably quantifying and monitoring visual processing and treatment efficiency in patient populations. This paper aims to draw a current picture of key findings in this field so far, the challenges of using neuroimaging methods in patients with LHON, and important open questions that MRI can help address about LHON disease mechanisms and prognoses, including how downstream visual brain regions are affected by the disease and treatment and why, and how scope for neural plasticity in these pathways may limit or facilitate recovery

Poincare isomorphism in K-theory on manifolds with edges

The aim of this paper is to construct the Poincare isomorphism in K-theory on manifolds with edges. We show that the Poincare isomorphism can naturally be constructed in the framework of noncommutative geometry. More precisely, to a manifold with edges we assign a noncommutative algebra and construct an isomorphism between the K-group of this algebra and the K-homology group of the manifold with edges viewed as a compact topological space.Comment: 15 pages, no figure

Development and validation study of a non-alcoholic fatty liver disease risk scoring model among adults in China

Background: Non-alcoholic fatty liver disease (NAFLD) is one of the most common liver diseases in China. It is usually asymptomatic and transabdominal ultrasound (USS) is the usual means for diagnosis, but it may not be feasible to have USS screening of the whole population. Objective: To develop a risk scoring model for predicting the presence of NAFLD using parameters that can be easily obtain in clinical settings. Methods: A retrospective study on the data of 672 adults who had general health check including a transabdominal ultrasound. Fractional polynomial and multivariable logistic regressions of sociodemographic and biochemical variables on NAFLD were used to identify the predictors. A risk score was assigned to each predictor using the scaled standardized β-coefficient to create a risk prediction algorithm. The accuracy for NAFLD detection by each cut-off score in the risk algorithm was evaluated. Results: The prevalence of NAFLD in our study population was 33.0% (222/672). Six significant factors were selected in the final prediction model. The areas under the curve (AUC) was 0.82 (95% CI: 0.78–0.85). The optimal cut-off score, based on the ROC was 35, with a sensitivity of 76.58% (95% CI: 70.44–81.98%) and specificity of 74.89% (95% CI: 70.62–78.83%). Conclusion: A NAFLD risk scoring model can be used to identify asymptomatic Chinese people who are at risk of NAFLD for further USS investigation.published_or_final_versio

A Factorization Law for Entanglement Decay

We present a simple and general factorization law for quantum systems shared by two parties, which describes the time evolution of entanglement upon passage of either component through an arbitrary noisy channel. The robustness of entanglement-based quantum information processing protocols is thus easily and fully characterized by a single quantity.Comment: 4 pages, 5 figure

Prenatal Vitamin D Supplementation and Child Respiratory Health: A Randomised Controlled Trial

PMCID: PMC3691177This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Wall Crossing and Instantons in Compactified Gauge Theory

We calculate the leading weak-coupling instanton contribution to the moduli-space metric of N=2 supersymmetric Yang-Mills theory with gauge group SU(2) compactified on R^3 x S^1. The results are in precise agreement with the semiclassical expansion of the exact metric recently conjectured by Gaiotto, Moore and Neitzke based on considerations related to wall-crossing in the corresponding four-dimensional theory.Comment: 24 pages, no figure