Spitzer Limits On Dust Emission and Optical Gas Absorption Variability Around Nearby Stars with Edge-On Circumstellar Disk Signatures

We present Spitzer observations and McDonald Observatory Smith Telescope and Anglo-Australian Telescope high spectral resolution optical observations of 4 nearby stars with variable or anomalous optical absorption, likely caused by circumstellar material. The optical observations of CaII and NaI cover a 2.8 year baseline, and extend the long term monitoring of these systems by previous researchers. In addition, mini-surveys of the local interstellar medium (LISM) around our primary targets provide a reconstruction of the intervening LISM along the line of sight. We confirm that the anomalous absorption detected toward alpha Oph is not due to circumstellar material, but to a small filamentary cloud <14.3 pc from the Sun. The three other primary targets, beta Car, HD85905, and HR10 show both short and long term variability, and little of the observed absorption can be attributed to the LISM along the line of sight. The Spitzer observations did not detect infrared excesses. We are able to place upper limits on any possible fractional infrared luminosity, which range from L_IR/L_star < 2-5 10^-6, for our three disk stars. No stable gas absorption component centered at the radial velocity of the star is detected for any of our targets. Based on simple assumptions of the variable gas absorption component, we estimate limits on the circumstellar gas mass causing the variable absorption, which range from 0.4-20 10^-8 M_Earth. These multiwavelength observations place strong limits on any possible circumstellar dust, while confirming variable circumstellar gas absorption, and therefore are interesting targets to explore the origins and evolution of variable circumstellar gas. (abridged)Comment: 65 pages, 16 figures; Accepted for publication in Ap

Imaging an Adapted Dentoalveolar Complex

Adaptation of a rat dentoalveolar complex was illustrated using various imaging modalities. Micro-X-ray computed tomography for 3D modeling, combined with complementary techniques, including image processing, scanning electron microscopy, fluorochrome labeling, conventional histology (H&E, TRAP), and immunohistochemistry (RANKL, OPN) elucidated the dynamic nature of bone, the periodontal ligament-space, and cementum in the rat periodontium. Tomography and electron microscopy illustrated structural adaptation of calcified tissues at a higher resolution. Ongoing biomineralization was analyzed using fluorochrome labeling, and by evaluating attenuation profiles using virtual sections from 3D tomographies. Osteoclastic distribution as a function of anatomical location was illustrated by combining histology, immunohistochemistry, and tomography. While tomography and SEM provided past resorption-related events, future adaptive changes were deduced by identifying matrix biomolecules using immunohistochemistry. Thus, a dynamic picture of the dentoalveolar complex in rats was illustrated

Effects of increasing the affinity of CarD for RNA polymerase on Mycobacterium tuberculosis growth, rRNA transcription, and virulence

CarD is an essential RNA polymerase (RNAP) interacting protein in Mycobacterium tuberculosis that stimulates formation of RNAP-promoter open complexes. CarD plays a complex role in M. tuberculosis growth and virulence that is not fully understood. Therefore, to gain further insight into the role of CarD in M. tuberculosis growth and virulence, we determined the effect of increasing the affinity of CarD for RNAP. Using site-directed mutagenesis guided by crystal structures of CarD bound to RNAP, we identified amino acid substitutions that increase the affinity of CarD for RNAP. Using these substitutions, we show that increasing the affinity of CarD for RNAP increases the stability of the CarD protein in M. tuberculosis. In addition, we show that increasing the affinity of CarD for RNAP increases the growth rate in M. tuberculosis without affecting 16S rRNA levels. We further show that increasing the affinity of CarD for RNAP reduces M. tuberculosis virulence in a mouse model of infection despite the improved growth rate in vitro. Our findings suggest that the CarD-RNAP interaction protects CarD from proteolytic degradation in M. tuberculosis, establish that growth rate and rRNA levels can be uncoupled in M. tuberculosis and demonstrate that the strength of the CarD-RNAP interaction has been finely tuned to optimize virulence. IMPORTANCE Mycobacterium tuberculosis, the causative agent of tuberculosis, remains a major global health problem. In order to develop new strategies to battle this pathogen, we must gain a better understanding of the molecular processes involved in its survival and pathogenesis. We have previously identified CarD as an essential transcriptional regulator in mycobacteria. In this study, we detail the effects of increasing the affinity of CarD for RNAP on transcriptional regulation, CarD protein stability, and virulence. These studies expand our understanding of the global transcription regulator CarD, provide insight into how CarD activity is regulated, and broaden our understanding of prokaryotic transcription

Searching for Intragroup Light in Deep U-band Imaging of the COSMOS Field

We present the results of deep, ground based U-band imaging with the Large Binocular Telescope of the Cosmic Evolution Survey (COSMOS) field as part of the near-UV imaging program, UVCANDELS. We utilize a seeing sorted stacking method along with night-to-night relative transparency corrections to create optimal depth and optimal resolution mosaics in the U-band, which are capable of reaching point source magnitudes of AB 26.5 mag at 3 sigma. These ground based mosaics bridge the wavelength gap between the HST WFC3 F27W and ACS F435W images and are necessary to understand galaxy assembly in the last 9-10 Gyr. We use the depth of these mosaics to search for the presence of U-band intragroup light (IGrL) beyond the local Universe. Regardless of how groups are scaled and stacked, we do not detect any U-band IGrL to unprecedented U-band depths of 29.1-29.6 mag/arcsec2, which corresponds to an IGrL fraction of less than 1% of the total group light. This stringent upper limit suggests that IGrL does not contribute significantly to the Extragalactic Background Light at short wavelengths. Furthermore, the lack of UV IGrL observed in these stacks suggests that the atomic gas observed in the intragroup medium (IGrM) is likely not dense enough to trigger star formation on large scales. Future studies may detect IGrL by creating similar stacks at longer wavelengths or by pre-selecting groups which are older and/or more dynamically evolved similar to past IGrL observations of compact groups and loose groups with signs of gravitational interactions.Comment: Accepted to PAS

JWST NIRCam Photometry: A Study of Globular Clusters Surrounding Bright Elliptical Galaxy VV 191a at z=0.0513

James Webb Space Telescope NIRCam images have revealed 443 globular cluster (GC) candidates around the $z=0.0513$ elliptical galaxy VV 191a. NIRCam broadband observations are made at 0.9-4.5 $\mu$m using filters F090W, F150W, F356W, and F444W. Using photometry, the data is analyzed to present color-magnitude diagrams (CMDs) that suggest a fairly uniform population of GCs. Color histograms show a unimodal color distribution that is well fit by a single Gaussian, using color to primarily trace the metallicity. The findings show the sample's globular cluster luminosity function (GCLF) does not reach the turnover value and is, therefore, more luminous than what is typically expected, with an absolute AB magnitude, $M_{F090W} = -8.70$ mag, reaching within nearly one magnitude of the classical turnover value. We attribute this to the completeness in the sample. Models show that the mass estimate of the GCs detected tends to be more massive, reaching upward of $\simeq 10^7 M_{\odot}$. However, the results show that current GC models do not quite align with the data. We find that the models appear to be bluer than the JWST data in the reddest (F356W-F444W) filters and redder than the data in the bluest (F090W-F150W) filters and may need to be revised to improve the modeling of near-IR colors of old, metal-poor stellar populations.Comment: 11 pages, 7 figure

Prostration and the prognosis of death in African children with severe malaria

Objectives: Malaria is still one of the main reasons for hospitalization in children living in sub-Saharan Africa. Rapid risk stratification at admission is essential for optimal medical care and improved prognosis. Whereas coma, deep breathing, and, to a lesser degree, severe anemia are established predictors of malaria-related death, the value of assessing prostration for risk stratification is less certain. Methods: Here we used a retrospective multi-center analysis comprising over 33,000 hospitalized children from four large studies, including two observational studies from the Severe Malaria in African Children network, a randomized controlled treatment study, and the phase-3-clinical RTS,S-malaria vaccine trial, to evaluate known risk factors of mortality and with a specific emphasis on the role of prostration. Results: Despite comparable age profiles of the participants, we found significant inter- and intra-study variation in the incidence of fatal malaria as well as in the derived risk ratios associated with the four risk factors: coma, deep breathing, anemia, and prostration. Despite pronounced variations, prostration was significantly associated with an increased risk of mortality (P <0.001) and its consideration resulted in improved predictive performance, both in a multivariate model and a univariate model based on the Lambaréné Organ Dysfunction Score. Conclusion: Prostration is an important clinical criterion to determine severe pediatric malaria with possible fatal outcomes

A population of gamma-ray emitting globular clusters seen with the Fermi Large Area Telescope

Globular clusters with their large populations of millisecond pulsars (MSPs) are believed to be potential emitters of high-energy gamma-ray emission. Our goal is to constrain the millisecond pulsar populations in globular clusters from analysis of gamma-ray observations. We use 546 days of continuous sky-survey observations obtained with the Large Area Telescope aboard the Fermi Gamma-ray Space Telescope to study the gamma-ray emission towards 13 globular clusters. Steady point-like high-energy gamma-ray emission has been significantly detected towards 8 globular clusters. Five of them (47 Tucanae, Omega Cen, NGC 6388, Terzan 5, and M 28) show hard spectral power indices $(0.7 < \Gamma <1.4)$ and clear evidence for an exponential cut-off in the range 1.0-2.6 GeV, which is the characteristic signature of magnetospheric emission from MSPs. Three of them (M 62, NGC 6440 and NGC 6652) also show hard spectral indices $(1.0 < \Gamma < 1.7)$, however the presence of an exponential cut-off can not be unambiguously established. Three of them (Omega Cen, NGC 6388, NGC 6652) have no known radio or X-ray MSPs yet still exhibit MSP spectral properties. From the observed gamma-ray luminosities, we estimate the total number of MSPs that is expected to be present in these globular clusters. We show that our estimates of the MSP population correlate with the stellar encounter rate and we estimate 2600-4700 MSPs in Galactic globular clusters, commensurate with previous estimates. The observation of high-energy gamma-ray emission from a globular cluster thus provides a reliable independent method to assess their millisecond pulsar populations that can be used to make constraints on the original neutron star X-ray binary population, essential for understanding the importance of binary systems in slowing the inevitable core collapse of globular clusters.Comment: Accepted for publication in A&A. Corresponding authors: J. Kn\"odlseder, N. Webb, B. Pancraz

Tracking Virus-Specific CD4+ T Cells during and after Acute Hepatitis C Virus Infection

CD4+ T cell help is critical in maintaining antiviral immune responses and such help has been shown to be sustained in acute resolving hepatitis C. In contrast, in evolving chronic hepatitis C CD4+ T cell helper responses appear to be absent or short-lived, using functional assays. Here we used a novel HLA-DR1 tetramer containing a highly targeted CD4+ T cell epitope from the hepatitis C virus non-structural protein 4 to track number and phenotype of hepatitis C virus specific CD4+ T cells in a cohort of seven HLA-DR1 positive patients with acute hepatitis C in comparison to patients with chronic or resolved hepatitis C. We observed peptide-specific T cells in all seven patients with acute hepatitis C regardless of outcome at frequencies up to 0.65% of CD4+ T cells. Among patients who transiently controlled virus replication we observed loss of function, and/or physical deletion of tetramer+ CD4+ T cells before viral recrudescence. In some patients with chronic hepatitis C very low numbers of tetramer+ cells were detectable in peripheral blood, compared to robust responses detected in spontaneous resolvers. Importantly we did not observe escape mutations in this key CD4+ T cell epitope in patients with evolving chronic hepatitis C. During acute hepatitis C a CD4+ T cell response against this epitope is readily induced in most, if not all, HLA-DR1+ patients. This antiviral T cell population becomes functionally impaired or is deleted early in the course of disease in those where viremia persists

Clinical impact of pretreatment human immunodeficiency virus drug resistance in people initiating nonnucleoside reverse transcriptase inhibitor-containing antiretroviral therapy: A systematic review and meta-analysis

Background: Increased access to antiretroviral therapy (ART) has resulted in rising levels of pretreatment human immunodeficiency virus drug resistance (PDR). This is the first systematic review and meta-analysis to assess the impact of PDR on treatment outcomes among people initiating nonnucleoside reverse transcriptase inhibitor (NNRTI)-based ART, including the combination of efavirenz (EFV), tenofovir (TDF), and lamivudine or emtricitabine (XTC). Methods: We systematically reviewed studies and conference proceedings comparing treatment outcomes in populations initiating NNRTI-based ART with and without PDR. We conducted subgroup analyses by regimen: (1) NNRTIs + 2 nucleoside reverse transcriptase inhibitors (NRTIs), (2) EFV + 2 NRTIs, or (3) EFV/TDF/XTC; by population (children vs adults); and by definition of resistance (PDR vs NNRTI PDR). Results: Among 6197 studies screened, 32 were analyzed (31 441 patients). We found that individuals with PDR initiating NNRTIs across all the subgroups had increased risk of virological failure compared to those without PDR. Risk of acquisition of new resistance mutations and ART switch was also higher in people with PDR. Conclusions: This review shows poorer treatment outcomes in the presence of PDR, supporting the World Health Organization's recommendation to avoid using NNRTIs in countries where levels of PDR are high

Clinical impact of pretreatment human immunodeficiency virus drug resistance in people initiating nonnucleoside reverse transcriptase inhibitor-containing antiretroviral therapy: a systematic review and meta-analysis

Background: Increased access to antiretroviral therapy (ART) has resulted in rising levels of pretreatment human immunodeficiency virus drug resistance (PDR). This is the first systematic review and meta-analysis to assess the impact of PDR on treatment outcomes among people initiating nonnucleoside reverse transcriptase inhibitor (NNRTI)-based ART, including the combination of efavirenz (EFV), tenofovir (TDF), and lamivudine or emtricitabine (XTC). Methods: We systematically reviewed studies and conference proceedings comparing treatment outcomes in populations initiating NNRTI-based ART with and without PDR. We conducted subgroup analyses by regimen: (1) NNRTIs + 2 nucleoside reverse transcriptase inhibitors (NRTIs), (2) EFV + 2 NRTIs, or (3) EFV/TDF/XTC; by population (children vs adults); and by definition of resistance (PDR vs NNRTI PDR). Results: Among 6197 studies screened, 32 were analyzed (31 441 patients). We found that individuals with PDR initiating NNRTIs across all the subgroups had increased risk of virological failure compared to those without PDR. Risk of acquisition of new resistance mutations and ART switch was also higher in people with PDR. Conclusions: This review shows poorer treatment outcomes in the presence of PDR, supporting the World Health Organization's recommendation to avoid using NNRTIs in countries where levels of PDR are high