Tomographic Magnification of Lyman Break Galaxies in The Deep Lens Survey

Using about 450,000 galaxies in the Deep Lens Survey, we present a detection of the gravitational magnification of z > 4 Lyman Break Galaxies by massive foreground galaxies with 0.4 < z < 1.0, grouped by redshift. The magnification signal is detected at S/N greater than 20, and rigorous checks confirm that it is not contaminated by any galaxy sample overlap in redshift. The inferred galaxy mass profiles are consistent with earlier lensing analyses at lower redshift. We then explore the tomographic lens magnification signal by splitting our foreground galaxy sample into 7 redshift bins. Combining galaxy-magnification cross-correlations and galaxy angular auto-correlations, we develop a bias-independent estimator of the tomographic signal. As a diagnostic of magnification tomography, the measurement of this estimator rejects a flat dark matter dominated Universe at > 7.5{\sigma} with a fixed \sigma_8 and is found to be consistent with the expected redshift-dependence of the WMAP7 {\Lambda}CDM cosmology.Comment: 12 pages, 9 figures, Accepted to MNRA

Expansion of Myeloid-Derived Suppressor Cells Promotes Differentiation of Regulatory T Cells in HIV-1+ Individuals

Objective: Regulatory T cells (Tregs) contribute to HIV-1 disease progression by impairing antiviral immunity; however, the precise mechanisms responsible for the development of Tregs in the setting of HIV-1 infection are incompletely understood. Design: In this study, we provide evidence that HIV-induced expansion of monocytic myeloid-derived suppressor cells (M-MDSCs) promote the differentiation of Foxp3+ Tregs. Methods: We measured MDSC induction and cytokine expression by flow cytometry and analyzed their functions by coculturing experiments. Results: We observed a dramatic increase in M-MDSC frequencies in the peripheral blood of HIV-1 seropositive (HIV-1+) individuals, even in those on antiretroviral therapy with undetectable viremia, when compared with healthy participants. We also observed increases in M-MDSCs after incubating healthy peripheral mononuclear cells (PBMCs) with HIV-1 proteins (gp120 or Tat) or Toll-like receptor 4 ligand lipopolysaccharides in vitro, an effect that could be abrogated in the presence of the phosphorylated signal transducer and activator of transcription 3 inhibitor, STA-21. Functional analyses indicated that M-MDSCs from HIV-1+ individuals express higher levels of IL-10, tumor growth factor-β, IL-4 receptor α, p47phex, programmed death-ligand 1, and phosphorylated signal transducer and activator of transcription 3 – all of which are known mediators of myelopoiesis and immunosuppression. Importantly, incubation of healthy CD4+ T cells with MDSCs derived from HIV-1+ individuals significantly increased differentiation of Foxp3+ Tregs. In addition, depletion of MDSCs from PBMCs of HIV-1+ individuals led to a significant reduction of Foxp3+ Tregs and increase of IFNγ production by CD4+ T effector cells. Conclusions: These results suggest that HIV-induced MDSCs promote Treg cell development and inhibit T cell function – a hallmark of many chronic infectious diseases

Detection of a Thick Disk in the edge-on Low Surface Brightness Galaxy ESO 342-G017: I. VLT Photometry in V and R Bands

We report the detection of a thick disk in the edge-on, low surface brightness (LSB), late-type spiral ESO 342-G017, based on ultra-deep images in the V and R bands obtained with the VLT Test Camera during Science Verification on UT1. All steps in the reduction procedure are fully described, which, together with an extensive analysis of systematic and statistic uncertainties, has resulted in surface brightness photometry that is reliable for the detection of faint extended structure to a level of V = 27.5 and R = 28.5 mag/square arcsec. The faint light apparent in these deep images is well-modeled by a thick exponential disk with an intrinsic scale height about 2.5 times that of the thin disk, and a comparable or somewhat larger scale length. Deprojection including the effects of inclination and convolution with the PSF allow us to estimate that the thick disk contributes 20-40% of the total (old) stellar disk luminosity of ESO 342-G017. To our knowledge, this is the first detection of a thick disk in an LSB galaxy, which are generally thought to be rather unevolved compared to higher surface brightness galaxies.Comment: Accepted for publication in Astronomy & Astrophysics; 18 pages, 12 figure

Observational constraints on the physics behind the evolution of AGN since z ~ 1

We explore the evolution with redshift of the rest-frame colours and space densities of AGN hosts (relative to normal galaxies) to shed light on the dominant mechanism that triggers accretion onto supermassive black holes as a function of cosmic time. Data from serendipitous wide-area XMM surveys of the SDSS footprint (XMM/SDSS, Needles in the Haystack survey) are combined with Chandra deep observations in the AEGIS, GOODS-North and GOODS-South to compile uniformly selected samples of moderate luminosity X-ray AGN [L_X(2-10keV) = 1e41-1e44erg/s] at redshifts 0.1, 0.3 and 0.8. It is found that the fraction of AGN hosted by red versus blue galaxies does not change with redshift. Also, the X-ray luminosity density associated with either red or blue AGN hosts remains nearly constant since z=0.8. X-ray AGN represent a roughly fixed fraction of the space density of galaxies of given optical luminosity at all redshifts probed by our samples. In contrast the fraction of X-ray AGN among galaxies of a given stellar mass decreases with decreasing redshift. These findings suggest that the same process or combination of processes for fueling supermassive black holes are in operation in the last 5 Gyrs of cosmic time. The data are consistent with a picture in which the drop of the accretion power during that period (1dex since z=0.8) is related to the decline of the space density of available AGN hosts, as a result of the evolution of the specific star-formation rate of the overall galaxy population. Scenarios which attribute the evolution of moderate luminosity AGN since z \approx 1 to changes in the suppermassive black hole accretion mode are not favored by our results.Comment: MNRAS accepted, 15 pages, 10 figure

Topological DNA Damage, Telomere Attrition and T Cell Senescence During Chronic Viral Infections

Background: T cells play a key role in controlling viral infections; however, the underlying mechanisms regulating their functions during human viral infections remain incompletely understood. Here, we used CD4 T cells derived from individuals with chronic viral infections or healthy T cells treated with camptothecin (CPT) - a topoisomerase I (Top 1) inhibitor - as a model to investigate the role of DNA topology in reprogramming telomeric DNA damage responses (DDR) and remodeling T cell functions. Results: We demonstrated that Top 1 protein expression and enzyme activity were significantly inhibited, while the Top 1 cleavage complex (TOP1cc) was trapped in genomic DNA, in T cells derived from individuals with chronic viral (HCV, HBV, or HIV) infections. Top 1 inhibition by CPT treatment of healthy CD4 T cells caused topological DNA damage, telomere attrition, and T cell apoptosis or dysfunction via inducing Top1cc accumulation, PARP1 cleavage, and failure in DNA repair, thus recapitulating T cell dysregulation in the setting of chronic viral infections. Moreover, T cells from virally infected subjects with inhibited Top 1 activity were more vulnerable to CPT-induced topological DNA damage and cell apoptosis, indicating an important role for Top 1 in securing DNA integrity and cell survival. Conclusion: These findings provide novel insights into the molecular mechanisms for immunomodulation by chronic viral infections via disrupting DNA topology to induce telomeric DNA damage, T cell senescence, apoptosis and dysfunction. As such, restoring the impaired DNA topologic machinery may offer a new strategy for maintaining T cell function against human viral diseases

Mitochondrial Functions Are Compromised in CD4 T Cells From ART-Controlled PLHIV

The hallmark of HIV/AIDS is a gradual depletion of CD4 T cells. Despite effective control by antiretroviral therapy (ART), a significant subgroup of people living with HIV (PLHIV) fails to achieve complete immune reconstitution, deemed as immune non-responders (INRs). The mechanisms underlying incomplete CD4 T cell recovery in PLHIV remain unclear. In this study, CD4 T cells from PLHIV were phenotyped and functionally characterized, focusing on their mitochondrial functions. The results show that while total CD4 T cells are diminished, cycling cells are expanded in PLHIV, especially in INRs. HIV-INR CD4 T cells are more activated, displaying exhausted and senescent phenotypes with compromised mitochondrial functions. Transcriptional profiling and flow cytometry analysis showed remarkable repression of mitochondrial transcription factor A (mtTFA) in CD4 T cells from PLHIV, leading to abnormal mitochondrial and T cell homeostasis. These results demonstrate a sequential cellular paradigm of T cell over-activation, proliferation, exhaustion, senescence, apoptosis, and depletion, which correlates with compromised mitochondrial functions. Therefore, reconstituting the mtTFA pathway may provide an adjunctive immunological approach to revitalizing CD4 T cells in ART-treated PLHIV, especially in INRs

Disruption of Telomere Integrity and DNA Repair Machineries by KML001 Induces T Cell Senescence, Apoptosis, and Cellular Dysfunctions

T cells in chronic viral infections are featured by premature aging with accelerated telomere erosion, but the mechanisms underlying telomere attrition remain unclear. Here, we employed human CD4 T cells treated with KML001 (a telomere-targeting drug) as a model to investigate the role of telomere integrity in remodeling T cell senescence. We demonstrated that KML001 could inhibit cell proliferation, cytokine production, and promote apoptosis via disrupting telomere integrity and DNA repair machineries. Specifically, KML001-treated T cells increased dysfunctional telomere-induced foci (TIF), DNA damage marker γH2AX, and topoisomerase cleavage complex (TOPcc) accumulation, leading to telomere attrition. Mechanistically, KML001 compromised telomere integrity by inhibiting telomeric repeat binding factor 2 (TRF2), telomerase, topoisomerase I and II alpha (Top1/2a), and ataxia telangiectasia mutated (ATM) kinase activities. Importantly, these KML001-induced telomeric DNA damage and T cell senescent phenotype and machineries recapitulated our findings in patients with clinical HCV or HIV infection in that their T cells were also senescent with short telomeres and thus more vulnerable to KML001-induced apoptosis. These results shed new insights on the T cell aging network that is critical and essential in protecting chromosomal telomeres from unwanted DNA damage and securing T cell survival during cell crisis upon genomic insult

Search for the Decay τ−→4pi−3π+(π0)ντ\tau^{-}\to 4pi^{-}3\pi^{+}(\pi^{0})\nu_{\tau}

We have searched for the decay of the tau lepton into seven charged particles and zero or one pi0. The data used in the search were collected with the CLEO II detector at the Cornell Electron Storage Ring (CESR) and correspond to an integrated luminosity of 4.61 fb^(-1). No evidence for a signal is found. Assuming all the charged particles are pions, we set an upper limit on the branching fraction, B(tau- -> 4pi- 3pi+ (pi0) nu_tau) < 2.4 x 10^(-6) at the 90% confidence level. This limit represents a significant improvement over the previous limit.Comment: 9 page postscript file, postscript file also available through http://w4.lns.cornell.edu/public/CLN

Flavor-Specific Inclusive B Decays to Charm

We have measured the branching fractions for B -> D_bar X, B -> D X, and B -> D_bar X \ell^+ \nu, where ``B'' is an average over B^0 and B^+, ``D'' is a sum over D^0 and D^+, and``D_bar'' is a sum over D^0_bar and D^-. From these results and some previously measured branching fractions, we obtain Br(b -> c c_bar s) = (21.9 $\pm$ 3.7)%, Br(b -> s g) K^- \pi^+) = (3.69 $\pm$ 0.20)%. Implications for the ``B semileptonic decay problem'' (measured branching fraction being below theoretical expectations) are discussed. The increase in the value of Br(b -> c c_bar s) due to $B -> D X$ eliminates 40% of the discrepancy.Comment: 12 page postscript file, postscript file also available through http://w4.lns.cornell.edu/public/CLN