Constraints on cross-section and lifetime of dark matter with HAWC Observations of dwarf Irregular galaxies

It has been shown that the dynamics of dwarf Irregular (dIrr) galaxies are dominated by dark matter. It is also observed that these galaxies have low star formation rates and metallicities, and no gamma-ray emission at ultra very high energies is expected. Because of their distance, dark matter content and vast number, dIrr galaxies are good targets to perform indirect dark matter searches by ground-based and wide field of view gamma-ray experiments, like HAWC. We analyzed data at the position of 31 dIrr galaxies within the HAWC field-of-view and no significant excess was found. Here, we present the individual and combined limits on the annihilation cross-section and decay lifetime of weakly interacting massive particles with mass between 1 and 100 TeV

Searching for TeV DM evidence from Dwarf Irregular Galaxies with the HAWC Observatory

The dynamics of dwarf irregular (dIrr) galaxies are observed to be dominated by dark matter (DM). Recently, the DM density distribution has been studied for 31 dIrrs. Their extended DM halo (Burket type profile) makes these objects good candidates for DM searches. Located in Puebla (Mexico), the High Altitude Water Cherenkov (HAWC) Observatory is an optimal instrument to perform such DM searches, because of its large sky coverage (8.4 sr per day). We analyzed a set of two years of HAWC data and we found no significant DM signal from dIrr galaxies. We present the upper limits for DM annihilation cross-section with dIrr galaxies

Decreased Expression of Negative Immune Checkpoint VISTA by CD4+T Cells Facilitates T Helper 1, T Helper 17, and T Follicular Helper Lineage Differentiation in GCA

Loss of immune checkpoint (IC) Programmed Death-1 (PD-1) and PD-Ligand1 (PD-L1) expression has been implicated in the immunopathology of Giant Cell Arteritis (GCA). The contribution of the negative immune checkpoint V-domain Immunoglobulin-containing suppressor of T cell activation (VISTA) to GCA pathology has not yet been studied. The aim of our study was to investigate if expression of VISTA and other IC molecules by peripheral blood (PB) immune cells is modulated in GCA and at the site of vascular inflammation. In addition, we assessed the effect of VISTA-Ig engagement on in vitro CD4+ T helper (Th) lineage differentiation. To this end, frequencies of monocytes expressing CD80/86, PD-L1, PD-L2, and VISTA were determined in blood samples from 30 GCA patients and 18 matched healthy controls by flow cytometry. In parallel, frequencies of CD4+ cells expressing CD28, Cytotoxic T-Lymphocyte-associated antigen-4 (CTLA-4), PD-1, and VISTA were determined. Immunohistochemistry was employed to detect VISTA, PD-1, and PD-L1-expressing cells in temporal artery biopsies (TABs) diagnostic of GCA. Furthermore, the effect of VISTA-Ig on in vitro CD4+ Th lineage differentiation in patients and controls was determined. Our study shows that frequencies of CD80/CD86+ and VISTA+ monocytes were decreased in treated GCA patients only. Moreover, proportions of PD-1+ and VISTA+ Th cells were significantly decreased in GCA patients. Clear infiltration of VISTA+, PD1+, and PD-L1+ cells was seen in GCA TABs. Finally, VISTA-Ig engagement failed to suppress Th1, Th17, and Tfh lineage development in GCA. Our results indicate that decreased expression of VISTA may facilitate development of pathogenic Th1 and Th17 cells in GCA

VPR-Bench: An Open-Source Visual Place Recognition Evaluation Framework with Quantifiable Viewpoint and Appearance Change

Visual place recognition (VPR) is the process of recognising a previously visited place using visual information, often under varying appearance conditions and viewpoint changes and with computational constraints. VPR is related to the concepts of localisation, loop closure, image retrieval and is a critical component of many autonomous navigation systems ranging from autonomous vehicles to drones and computer vision systems. While the concept of place recognition has been around for many years, VPR research has grown rapidly as a field over the past decade due to improving camera hardware and its potential for deep learning-based techniques, and has become a widely studied topic in both the computer vision and robotics communities. This growth however has led to fragmentation and a lack of standardisation in the field, especially concerning performance evaluation. Moreover, the notion of viewpoint and illumination invariance of VPR techniques has largely been assessed qualitatively and hence ambiguously in the past. In this paper, we address these gaps through a new comprehensive open-source framework for assessing the performance of VPR techniques, dubbed “VPR-Bench”. VPR-Bench (Open-sourced at: https://github.com/MubarizZaffar/VPR-Bench) introduces two much-needed capabilities for VPR researchers: firstly, it contains a benchmark of 12 fully-integrated datasets and 10 VPR techniques, and secondly, it integrates a comprehensive variation-quantified dataset for quantifying viewpoint and illumination invariance. We apply and analyse popular evaluation metrics for VPR from both the computer vision and robotics communities, and discuss how these different metrics complement and/or replace each other, depending upon the underlying applications and system requirements. Our analysis reveals that no universal SOTA VPR technique exists, since: (a) state-of-the-art (SOTA) performance is achieved by 8 out of the 10 techniques on at least one dataset, (b) SOTA technique in one community does not necessarily yield SOTA performance in the other given the differences in datasets and metrics. Furthermore, we identify key open challenges since: (c) all 10 techniques suffer greatly in perceptually-aliased and less-structured environments, (d) all techniques suffer from viewpoint variance where lateral change has less effect than 3D change, and (e) directional illumination change has more adverse effects on matching confidence than uniform illumination change. We also present detailed meta-analyses regarding the roles of varying ground-truths, platforms, application requirements and technique parameters. Finally, VPR-Bench provides a unified implementation to deploy these VPR techniques, metrics and datasets, and is extensible through templates

The Clinical Promise of Biomarkers of Synapse Damage or Loss in Alzheimer’s Disease

BACKGROUND: Synapse damage and loss are fundamental to the pathophysiology of Alzheimer's disease (AD) and lead to reduced cognitive function. The goal of this review is to address the challenges of forging new clinical development approaches for AD therapeutics that can demonstrate reduction of synapse damage or loss. The key points of this review include the following: Synapse loss is a downstream effect of amyloidosis, tauopathy, inflammation, and other mechanisms occurring in AD.Synapse loss correlates most strongly with cognitive decline in AD because synaptic function underlies cognitive performance.Compounds that halt or reduce synapse damage or loss have a strong rationale as treatments of AD.Biomarkers that measure synapse degeneration or loss in patients will facilitate clinical development of such drugs.The ability of methods to sensitively measure synapse density in the brain of a living patient through synaptic vesicle glycoprotein 2A (SV2A) positron emission tomography (PET) imaging, concentrations of synaptic proteins (e.g., neurogranin or synaptotagmin) in the cerebrospinal fluid (CSF), or functional imaging techniques such as quantitative electroencephalography (qEEG) provides a compelling case to use these types of measurements as biomarkers that quantify synapse damage or loss in clinical trials in AD. CONCLUSION: A number of emerging biomarkers are able to measure synapse injury and loss in the brain and may correlate with cognitive function in AD. These biomarkers hold promise both for use in diagnostics and in the measurement of therapeutic successes

The effect of HIV-1 Vif polymorphisms on A3G anti-viral activity in an in vivo mouse model

Abstract Humans encode seven APOBEC3 proteins (A–H), with A3G, 3F and 3H as the major factors restricting HIV-1 replication. HIV-1, however, encodes Vif, which counteracts A3 proteins by chaperoning them to the proteasome where they are degraded. Vif polymorphisms found in HIV-1s isolated from infected patients have varying anti-A3G potency when assayed in vitro, but there are few studies demonstrating this in in vivo models. Here, we created Friend murine leukemia viruses encoding vif alleles that were previously shown to differentially neutralize A3G in cell culture or that were originally found in primary HIV-1 isolates. Infection of transgenic mice expressing different levels of human A3G showed that these naturally occurring Vif variants differed in their ability to counteract A3G during in vivo infection, although the effects on viral replication were not identical to those seen in cultured cells. We also found that the polymorphic Vifs that attenuated viral replication reverted to wild type only in A3G transgenic mice. Finally, we found that the level of A3G-mediated deamination was inversely correlated with the level of viral replication. This animal model should be useful for studying the functional significance of naturally occurring vif polymorphisms, as well as viral evolution in the presence of A3G