Dark Matter Constraints from a Joint Analysis of Dwarf Spheroidal Galaxy Observations with VERITAS

We present constraints on the annihilation cross section of WIMP dark matter based on the joint statistical analysis of four dwarf galaxies with VERITAS. These results are derived from an optimized photon weighting statistical technique that improves on standard imaging atmospheric Cherenkov telescope (IACT) analyses by utilizing the spectral and spatial properties of individual photon events. We report on the results of $\sim$230 hours of observations of five dwarf galaxies and the joint statistical analysis of four of the dwarf galaxies. We find no evidence of gamma-ray emission from any individual dwarf nor in the joint analysis. The derived upper limit on the dark matter annihilation cross section from the joint analysis is $1.35\times 10^{-23} {\mathrm{ cm^3s^{-1}}}$ at 1 TeV for the bottom quark ($b\bar{b}$) final state, $2.85\times 10^{-24}{\mathrm{ cm^3s^{-1}}}$ at 1 TeV for the tau lepton ($\tau^{+}\tau^{-}$) final state and $1.32\times 10^{-25}{\mathrm{ cm^3s^{-1}}}$ at 1 TeV for the gauge boson ($\gamma\gamma$) final state.Comment: 14 pages, 9 figures, published in PRD, Ascii tables containing annihilation cross sections limits are available for download as ancillary files with readme.txt file description of limit

Very-High-Energy γ\gamma-Ray Observations of the Blazar 1ES 2344+514 with VERITAS

We present very-high-energy $\gamma$-ray observations of the BL Lac object 1ES 2344+514 taken by the Very Energetic Radiation Imaging Telescope Array System (VERITAS) between 2007 and 2015. 1ES 2344+514 is detected with a statistical significance above background of $20.8\sigma$ in $47.2$ hours (livetime) of observations, making this the most comprehensive very-high-energy study of 1ES 2344+514 to date. Using these observations the temporal properties of 1ES 2344+514 are studied on short and long times scales. We fit a constant flux model to nightly- and seasonally-binned light curves and apply a fractional variability test, to determine the stability of the source on different timescales. We reject the constant-flux model for the 2007-2008 and 2014-2015 nightly-binned light curves and for the long-term seasonally-binned light curve at the $> 3\sigma$ level. The spectra of the time-averaged emission before and after correction for attenuation by the extragalactic background light are obtained. The observed time-averaged spectrum above 200 GeV is satisfactorily fitted (${\chi^2/NDF = 7.89/6}$) by a power-law function with index $\Gamma = 2.46 \pm 0.06_{stat} \pm 0.20_{sys}$ and extends to at least 8 TeV. The extragalactic-background-light-deabsorbed spectrum is adequately fit (${\chi^2/NDF = 6.73/6}$) by a power-law function with index $\Gamma = 2.15 \pm 0.06_{stat} \pm 0.20_{sys}$ while an F-test indicates that the power-law with exponential cutoff function provides a marginally-better fit ($\chi^2/NDF$ = $2.56 / 5$) at the 2.1$\sigma$ level. The source location is found to be consistent with the published radio location and its spatial extent is consistent with a point source.Comment: 7 pages, 2 figures. Published in Monthly Notices of the Royal Astronomical Societ

A search for spectral hysteresis and energy-dependent time lags from X-ray and TeV gamma-ray observations of Mrk 421

Blazars are variable emitters across all wavelengths over a wide range of timescales, from months down to minutes. It is therefore essential to observe blazars simultaneously at different wavelengths, especially in the X-ray and gamma-ray bands, where the broadband spectral energy distributions usually peak. In this work, we report on three "target-of-opportunity" (ToO) observations of Mrk 421, one of the brightest TeV blazars, triggered by a strong flaring event at TeV energies in 2014. These observations feature long, continuous, and simultaneous exposures with XMM-Newton (covering X-ray and optical/ultraviolet bands) and VERITAS (covering TeV gamma-ray band), along with contemporaneous observations from other gamma-ray facilities (MAGIC and Fermi-LAT) and a number of radio and optical facilities. Although neither rapid flares nor significant X-ray/TeV correlation are detected, these observations reveal subtle changes in the X-ray spectrum of the source over the course of a few days. We search the simultaneous X-ray and TeV data for spectral hysteresis patterns and time delays, which could provide insight into the emission mechanisms and the source properties (e.g. the radius of the emitting region, the strength of the magnetic field, and related timescales). The observed broadband spectra are consistent with a one-zone synchrotron self-Compton model. We find that the power spectral density distribution at $\gtrsim 4\times 10^{-4}$ Hz from the X-ray data can be described by a power-law model with an index value between 1.2 and 1.8, and do not find evidence for a steepening of the power spectral index (often associated with a characteristic length scale) compared to the previously reported values at lower frequencies.Comment: 45 pages, 15 figure

Calmodulin-like proteins localized to the conoid regulate motility and cell invasion by Toxoplasma gondii

Toxoplasma gondii contains an expanded number of calmodulin (CaM)-like proteins whose functions are poorly understood. Using a combination of CRISPR/Cas9-mediated gene editing and a plant-like auxin-induced degron (AID) system, we examined the roles of three apically localized CaMs. CaM1 and CaM2 were individually dispensable, but loss of both resulted in a synthetic lethal phenotype. CaM3 was refractory to deletion, suggesting it is essential. Consistent with this prediction auxin-induced degradation of CaM3 blocked growth. Phenotypic analysis revealed that all three CaMs contribute to parasite motility, invasion, and egress from host cells, and that they act downstream of microneme and rhoptry secretion. Super-resolution microscopy localized all three CaMs to the conoid where they overlap with myosin H (MyoH), a motor protein that is required for invasion. Biotinylation using BirA fusions with the CaMs labeled a number of apical proteins including MyoH and its light chain MLC7, suggesting they may interact. Consistent with this hypothesis, disruption of MyoH led to degradation of CaM3, or redistribution of CaM1 and CaM2. Collectively, our findings suggest these CaMs may interact with MyoH to control motility and cell invasion

A network analysis to identify mediators of germline-driven differences in breast cancer prognosis.

Identifying the underlying genetic drivers of the heritability of breast cancer prognosis remains elusive. We adapt a network-based approach to handle underpowered complex datasets to provide new insights into the potential function of germline variants in breast cancer prognosis. This network-based analysis studies ~7.3 million variants in 84,457 breast cancer patients in relation to breast cancer survival and confirms the results on 12,381 independent patients. Aggregating the prognostic effects of genetic variants across multiple genes, we identify four gene modules associated with survival in estrogen receptor (ER)-negative and one in ER-positive disease. The modules show biological enrichment for cancer-related processes such as G-alpha signaling, circadian clock, angiogenesis, and Rho-GTPases in apoptosis

Centric diatoms of large rivers and tributaries in Hungary: morphology and biogeographic distribution

Centric diatoms of 107 different Hungarian running waters were investigated. Among them the largest was the River Danube, from which more than one hundred plankton samples were analysed by scanning electron microscopy (SEM). Only one sample was analysed from creeks, which were the smallest running waters analysed in this study. There were also channels with slow currents flowing out of rivers or connecting different rivers.In total, 41 centric taxa belonging to 11 genera were found during this study. The average number of taxa found in a single watercourse was 7, the maximum 40 and the minimum 1. Cyclotella meneghiniana was the most frequently encountered species (present in 60% ofsites). Twelve taxa were found in more than 20% of sites, 7 taxa between 5–10% and 6 taxa only in one site

Applications of Site-Specific Labeling to Study HAMLET, a Tumoricidal Complex of α-Lactalbumin and Oleic Acid

umor cells), and its tumoricidal activity has been well established.-acetylgalactosaminyltransferase II (ppGalNAc-T2) and further conjugated with aminooxy-derivatives of fluoroprobe or biotin molecules.We found that the molten globule form of hLA and αD-hLA proteins, with or without C-terminal extension, and with and without the conjugated fluoroprobe or biotin molecule, readily form a complex with OA and exhibits tumoricidal activity similar to HAMLET made with full-length hLA protein. The confocal microscopy studies with fluoroprobe-labeled samples show that these proteins are internalized into the cells and found even in the nucleus only when they are complexed with OA. The HAMLET conjugated with a single biotin molecule will be a useful tool to identify the cellular components that are involved with it in the tumoricidal activity