This catalog summarizes 117 high-confidence 0.1 GeV gamma-ray pulsar detections using three years of data acquired by the Large Area Telescope (LAT) on the Fermi satellite. Half are neutron stars discovered using LAT data through periodicity searches in gamma-ray and radio data around LAT unassociated source positions. The 117 pulsars are evenly divided into three groups: millisecond pulsars, young radio-loud pulsars, and young radio-quiet pulsars. We characterize the pulse profiles and energy spectra and derive luminosities when distance information exists. Spectral analysis of the off-peak phase intervals indicates probable pulsar wind nebula emission for four pulsars, and off-peak magnetospheric emission for several young and millisecond pulsars. We compare the gammaray properties with those in the radio, optical, and X-ray bands. We provide flux limits for pulsars with no observed gamma-ray emission, highlighting a small number of gamma-faint, radio-loud pulsars. The large, varied gamma-ray pulsar sample constrains emission models. Fermi's selection biases complement those of radio surveys, enhancing comparisons with predicted population distributions.

The third catalog of high-energy gamma-ray sources detected by the EGRET telescope on the Compton Gamma Ray Observatory includes data from 1991 April 22 to 1995 October 3 (cycles 1, 2, 3, and 4 of the mission). In addition to including more data than the second EGRET catalog and its supplement, this catalog uses completely reprocessed data (to correct a number of mostly minimal errors and problems). The 271 sources (E [ 100 MeV) in the catalog include the single 1991 solar Ñare bright enough to be detected as a source, the Large Magellanic Cloud, Ðve pulsars, one probable radio galaxy detection (Cen A), and 66 high-conÐdence identiÐcations of blazars (BL Lac objects, Ñat-spectrum radio quasars, or unidentiÐed Ñat-spectrum radio sources). In addition, 27 lower conÐdence potential blazar identiÐcations are noted. Finally, the catalog contains 170 sources not yet identiÐed Ðrmly with known objects, although potential identiÐcations have been suggested for a number of those. A Ðgure is presented that gives approximate upper limits for gamma-ray sources at any point in the sky, as well as information about sources listed in the second catalog and its supplement, that do not appear in this catalog.

We present the first catalog of active galactic nuclei (AGN) detected by the LAT, corresponding to 11 months of data collected in scientific operation mode. The First LAT AGN Catalog (1LAC) includes 671 γ-ray sources located at high Galactic latitudes (|b| > 10 •) that are detected with a test statistic (T S) greater than 25 and associated statistically with AGNs. Some LAT sources are associated with multiple AGNs, and consequently, the catalog includes 709 AGNs, comprising 300 BL Lacertae objects (BL Lacs), 296 flat-spectrum radio quasars (FSRQs), 41 AGNs of other types, and 72 AGNs of unknown type. We also classify the blazars based on their spectral energy distributions (SEDs) as archival radio, optical, and X-ray data permit. In addition to the formal 1LAC sample, we provide AGN associations for 51 low-latitude LAT sources and AGN "affiliations" (unquantified counterpart candidates) for 104 highlatitude LAT sources without AGN associations. The overlap of the 1LAC with existing γ-ray AGN catalogs (LBAS, EGRET, AGILE, Swift, INTEGRAL, TeVCat) is briefly discussed. Various properties-such as γ-ray fluxes and photon power law spectral indices, redshifts, γ-ray luminosities, variability, and archival radio luminosities-and their correlations are presented and discussed for the different blazar classes. We compare the 1LAC results with predictions regarding the γ-ray AGN populations, and we comment on the power of the sample to address the question of the blazar sequence.

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T cell immunoglobulin and mucin domain-containing-3 (Tim-3) is an inhibitory receptor expressed on exhausted T cells during HIV-1 and HCV infection. By contrast, Tim-3 expression and function are defective in multiple human autoimmune diseases. However, the molecular mechanisms governing Tim-3 function remain poorly understood. Here we show that HLA-B-associated transcript 3 (Bat3) binds to, and represses the function of Tim-3. Bat3-deficient T cells display elevated expression of exhaustion markers, and knocking down Bat3 in myelin antigen-specific CD4+ T cells dramatically inhibits the development of experimental autoimmune encephalomyelitis while promoting the expansion of a dysfunctional Tim-3hiIFNγlo CD4+ cell population. Furthermore, exhausted Tim-3+ T cells from murine tumors and HIV-1-infected individuals display substantially reduced Bat3 expression and targeted deletion of Bat3 induces an exhausted phenotype in T cells. These data indicate that Bat3 acts as a molecular safety catch that inhibits Tim-3-dependent cell death/exhaustion, suggesting that Bat3 may represent a viable therapeutic target in autoimmune disorders, chronic infections and cancers.

PcG proteins mediate heritable transcriptional silencing by generating and recognizing covalent histone modifications. One conserved PcG complex, PRC2, is composed of several proteins including the histone methyltransferase (HMTase) Ezh2, the WD-repeat protein Eed, and the Zn-finger protein Suz12. Ezh2 methylates histone H3 on lysine 27 (H3K27), which serves as an epigenetic mark mediating silencing. H3K27 can be mono-, di-, or trimethylated (1mH3K27, 2mH3K27, and 3mH3K27, respectively). Hence, either PRC2 must be regulated so as to add one methyl group to certain nucleosomes but two or three to others, or distinct complexes must be responsible for 1m-, 2m-, and 3mH3K27. Consistent with the latter possibility, 2mH3K27 and 3mH3K27, but not 1mH3K27, are absent in Suz12-/- embryos, which lack both Suz12 and Ezh2 protein. Mammalian proteins required for 1mH3K27 have not been identified. Here, we demonstrate that unlike Suz12 and Ezh2, Eed is required not only for 2m- and 3mH3K27 but also global 1mH3K27. These results provide a functionally important distinction between PRC2 complex components and implicate Eed in PRC2-independent histone methylation.

The well-known Crab Nebula is at the center of the SN1054 supernova remnant. It consists of a rotationally powered pulsar interacting with a surrounding nebula through a relativistic particle wind. The emissions originating from the pulsar and nebula have been considered to be essentially stable. Here, we report the detection of strong gamma-ray (100 mega-electron volts to 10 giga-electron volts) flares observed by the AGILE satellite in September 2010 and October 2007. In both cases, the total gamma-ray flux increased by a factor of three compared with the non-flaring flux. The flare luminosity and short time scale favor an origin near the pulsar, and we discuss Chandra Observatory x-ray and Hubble Space Telescope optical follow-up observations of the nebula. Our observations challenge standard models of nebular emission and require power-law acceleration by shock-driven plasma wave turbulence within an approximately 1-day time scale.

Genitourinary syndrome of menopause, a new term for a condition more renowned as atrophic vaginitis, is a hypoestrogenic condition with external genital, urological, and sexual implications that affects >50% of postmenopausal women. Due to sexual embarrassment and the sensitive nature of discussing symptoms, genitourinary syndrome of menopause is greatly underdiagnosed. The most up-to-date literature pertaining to clinical manifestations, pathophysiology, etiology, evaluation, and management of genitourinary syndrome of menopause is comprehensively reviewed. Early detection and individually tailored pharmacologic (eg, estrogen therapy, selective estrogen receptor modulator, synthetic steroid, oxytocin, and dehydroepiandrosterone) and/or nonpharmacologic (eg, laser therapies, moisturizers and lubricants, homeopathic remedies, and lifestyle modifications) treatment is paramount for not only improving quality of life but also for preventing exacerbation of symptoms in women with this condition.