JPSS-1/NOAA-20 VIIRS Early On-Orbit Geometric Performance

The first NOAA/NASA Join Polar Satellite System (JPSS-1) satellite was successfully launched on November 18, 2017,becoming NOAA-20. Instruments on-board the NOAA-20 satellite include the Visible Infrared Imaging RadiometerSuite (VIIRS). This instrument is the second build of VIIRS, with the first flight instrument on-board NASA/NOAASuomi National Polar-orbiting Partnership (SNPP) satellite operating since October 2011. The purpose of these VIIRSinstruments is to continue the long-term measurements of biogeophysical variables for multiple applications includingweather forecasting, rapid response and climate research. The geometric performance of VIIRS is essential to retrievingaccurate biogeophysical variables. This paper describes the early on-orbit geometric performance of the JPSS-1/NOAA-20 VIIRS. It first discusses the on-orbit orbit and attitude performance, a key input needed for accurate geolocation. Itthen discusses the on-orbit geometric characterization and calibration of VIIRS and an initial assessment of thegeometric accuracy. It follows with a discussion of an improvement in the instrument geometric model that correctssmall geometrical artifacts that appear in the along-scan direction. Finally, this paper discusses on-orbit measurements ofthe focal length and the impact of this on the scan-to-scan underlap/overlap

Overview of JPSS VIIRS Geometric Calibration and Validation

The presentation stressed the importance of a pre-launch test plan and a post-launch CalVal plan in the geometric aspects of instrument focal length, spatial responses, band-to-band registration, pointing, geolocation and long-term monitoring

Engineering HIV-Resistant Human CD4+ T Cells with CXCR4-Specific Zinc-Finger Nucleases

HIV-1 entry requires the cell surface expression of CD4 and either the CCR5 or CXCR4 coreceptors on host cells. Individuals homozygous for the ccr5Δ32 polymorphism do not express CCR5 and are protected from infection by CCR5-tropic (R5) virus strains. As an approach to inactivating CCR5, we introduced CCR5-specific zinc-finger nucleases into human CD4+ T cells prior to adoptive transfer, but the need to protect cells from virus strains that use CXCR4 (X4) in place of or in addition to CCR5 (R5X4) remains. Here we describe engineering a pair of zinc finger nucleases that, when introduced into human T cells, efficiently disrupt cxcr4 by cleavage and error-prone non-homologous DNA end-joining. The resulting cells proliferated normally and were resistant to infection by X4-tropic HIV-1 strains. CXCR4 could also be inactivated in ccr5Δ32 CD4+ T cells, and we show that such cells were resistant to all strains of HIV-1 tested. Loss of CXCR4 also provided protection from X4 HIV-1 in a humanized mouse model, though this protection was lost over time due to the emergence of R5-tropic viral mutants. These data suggest that CXCR4-specific ZFNs may prove useful in establishing resistance to CXCR4-tropic HIV for autologous transplant in HIV-infected individuals

Transmitted/Founder and Chronic Subtype C HIV-1 Use CD4 and CCR5 Receptors with Equal Efficiency and Are Not Inhibited by Blocking the Integrin α4β7

Sexual transmission of human immunodeficiency virus type 1 (HIV-1) most often results from productive infection by a single transmitted/founder (T/F) virus, indicating a stringent mucosal bottleneck. Understanding the viral traits that overcome this bottleneck could have important implications for HIV-1 vaccine design and other prevention strategies. Most T/F viruses use CCR5 to infect target cells and some encode envelope glycoproteins (Envs) that contain fewer potential N-linked glycosylation sites and shorter V1/V2 variable loops than Envs from chronic viruses. Moreover, it has been reported that the gp120 subunits of certain transmitted Envs bind to the gut-homing integrin α4β7, possibly enhancing virus entry and cell-to-cell spread. Here we sought to determine whether subtype C T/F viruses, which are responsible for the majority of new HIV-1 infections worldwide, share biological properties that increase their transmission fitness, including preferential α4β7 engagement. Using single genome amplification, we generated panels of both T/F (n = 20) and chronic (n = 20) Env constructs as well as full-length T/F (n = 6) and chronic (n = 4) infectious molecular clones (IMCs). We found that T/F and chronic control Envs were indistinguishable in the efficiency with which they used CD4 and CCR5. Both groups of Envs also exhibited the same CD4+ T cell subset tropism and showed similar sensitivity to neutralization by CD4 binding site (CD4bs) antibodies. Finally, saturating concentrations of anti-α4β7 antibodies failed to inhibit infection and replication of T/F as well as chronic control viruses, although the growth of the tissue culture-adapted strain SF162 was modestly impaired. These results indicate that the population bottleneck associated with mucosal HIV-1 acquisition is not due to the selection of T/F viruses that use α4β7, CD4 or CCR5 more efficiently

An HST/COS Survey of the Low-Redshift IGM. I. Survey, Methodology, & Overall Results

We use high-quality, medium-resolution {\it Hubble Space Telescope}/Cosmic Origins Spectrograph (\HST/COS) observations of 82 UV-bright AGN at redshifts $z_{AGN}<0.85$ to construct the largest survey of the low-redshift intergalactic medium (IGM) to date: 5343 individual extragalactic absorption lines in HI and 25 different metal-ion species grouped into 2610 distinct redshift systems at $z_{abs}<0.75$ covering total redshift pathlengths $\Delta z_{HI}=21.7$ and $\Delta z_{OVI}=14.5$. Our semi-automated line-finding and measurement technique renders the catalog as objectively-defined as possible. The cumulative column-density distribution of HI systems can be parametrized $dN(>N)/dz=C_{14}(N/10^{14} cm^{-2})^{-(\beta-1)}$, with $C_{14}=25\pm1$ and $\beta=1.65\pm0.02$. This distribution is seen to evolve both in amplitude, $C_{14}\sim(1+z)^{2.0\pm0.1}$, and slope $\beta(z)=1.73-0.26 z$ for $z<0.47$. We observe metal lines in 427 systems, and find that the fraction of IGM absorbers detected in metals is strongly dependent on N_{HI}. The distribution of OVI absorbers appear to evolve in the same sense as the Lya forest. We calculate contributions to $\Omega_b$ from different components of the low-$z$ IGM and determine the Lya decrement as a function of redshift. IGM absorbers are analyzed via a two-point correlation function (TPCF) in velocity space. We find substantial clustering of \HI\ absorbers on scales of $\Delta v=50-300$ km/s with no significant clustering at $\Delta v>1000$ km/s. Splitting the sample into strong and weak absorbers, we see that most of the clustering occurs in strong, $N_{HI}>10^{13.5} cm^{-2}$, metal-bearing IGM systems. The full catalog of absorption lines and fully-reduced spectra is available via MAST as a high-level science product at http://archive.stsci.edu/prepds/igm/.Comment: This is the accepted version (v3) of the paper. Previous versions (July 2015 and Feb. 2014) should be replaced by this one. In particular, please note that the associated MAST high-level-science product has been updated to reflect the of the final state of the paper. It is available at: http://archive.stsci.edu/prepds/igm

Early and Prolonged Antiretroviral Therapy Is Associated with an HIV-1-Specific T-Cell Profile Comparable to That of Long-Term Non-Progressors

Background: Intervention with antiretroviral treatment (ART) and control of viral replication at the time of HIV-1 seroconversion may curtail cumulative immunological damage. We have therefore hypothesized that ART maintenance over a very prolonged period in HIV-1 seroconverters could induce an immuno-virological status similar to that of HIV-1 long-term non-progressors (LTNPs).Methodology/Principal Findings: We have investigated a cohort of 20 HIV-1 seroconverters on long-term ART (LTTS) and compared it to one of 15 LTNPs. Residual viral replication and reservoirs in peripheral blood, as measured by cell-associated HIV-1 RNA and DNA, respectively, were demonstrated to be similarly low in both cohorts. These two virologically matched cohorts were then comprehensively analysed by polychromatic flow cytometry for HIV-1-specific CD4(+) and CD8(+) T-cell functional profile in terms of cytokine production and cytotoxic capacity using IFN-gamma, IL-2, TNF-alpha production and perforin expression, respectively. Comparable levels of highly polyfunctional HIV-1-specific CD4(+) and CD8(+) T-cells were found in LTTS and LTNPs, with low perforin expression on HIV-1-specific CD8+ T-cells, consistent with a polyfunctional/non-cytotoxic profile in a context of low viral burden.Conclusions: Our results indicate that prolonged ART initiated at the time of HIV-1 seroconversion is associated with immuno-virological features which resemble those of LTNPs, strengthening the recent emphasis on the positive impact of early treatment initiation and paving the way for further interventions to promote virological control after treatment interruption

HIV interactions with monocytes and dendritic cells: viral latency and reservoirs

HIV is a devastating human pathogen that causes serious immunological diseases in humans around the world. The virus is able to remain latent in an infected host for many years, allowing for the long-term survival of the virus and inevitably prolonging the infection process. The location and mechanisms of HIV latency are under investigation and remain important topics in the study of viral pathogenesis. Given that HIV is a blood-borne pathogen, a number of cell types have been proposed to be the sites of latency, including resting memory CD4+ T cells, peripheral blood monocytes, dendritic cells and macrophages in the lymph nodes, and haematopoietic stem cells in the bone marrow. This review updates the latest advances in the study of HIV interactions with monocytes and dendritic cells, and highlights the potential role of these cells as viral reservoirs and the effects of the HIV-host-cell interactions on viral pathogenesis