Phylogenetic evidence of HIV-1 sequence evolution in subjects with persistent low-level viremia

Persistent low-level viremia (LLV) during the treatment of antiretroviral therapy (ART) is associated with emergent drug resistance mutation (DRM); however insight into its driver is limited. The objectives were to study HIV-1 pol sequence evolution in subjects with persistent LLV and evaluate factors associated with sequence changes

Ground-Based Measurement Experiment and First Results with Geosynchronous-Imaging Fourier Transform Spectrometer Engineering Demonstration Unit

The geosynchronous-imaging Fourier transform spectrometer (GIFTS) engineering demonstration unit (EDU) is an imaging infrared spectrometer designed for atmospheric soundings. It measures the infrared spectrum in two spectral bands (14.6 to 8.8 microns, 6.0 to 4.4 microns) using two 128 x 128 detector arrays with a spectral resolution of 0.57 cm(exp -1) with a scan duration of approximately 11 seconds. From a geosynchronous orbit, the instrument will have the capability of taking successive measurements of such data to scan desired regions of the globe, from which atmospheric status, cloud parameters, wind field profiles, and other derived products can be retrieved. The GIFTS EDU provides a flexible and accurate testbed for the new challenges of the emerging hyperspectral era. The EDU ground-based measurement experiment, held in Logan, Utah during September 2006, demonstrated its extensive capabilities and potential for geosynchronous and other applications (e.g., Earth observing environmental measurements). This paper addresses the experiment objectives and overall performance of the sensor system with a focus on the GIFTS EDU imaging capability and proof of the GIFTS measurement concept

Antiretroviral Intensification and Valproic Acid Lack Sustained Effect on Residual HIV-1 Viremia or Resting CD4+ Cell Infection

Background: Human immunodeficiency virus (HIV) infection that persists despite antiretroviral therapy (ART) is a daunting problem. Given the limited evidence that resting CD4+ T cell infection (RCI) is affected by the histone deacetylase (HDAC) inhibitor valproic acid (VPA), we measured the stability of RCI and residual viremia in patients who added VPA with or without raltegravir (RAL), or enfuvirtide (ENF) with or without VPA, to standard ART. Methods: Patients with plasma HIV RNA,50 c/mL added sustained-release VPA (Depakote ERH) twice daily, RAL 400 mg twice daily, or ENF 90 mcg twice daily. Change in RCI was measured by outgrowth assays. Low-level viremia was quantitated by single-copy plasma HIV RNA assay (SCA). Results: In three patients on standard ART a depletion of RCI was observed after 16 weeks of VPA, but this effect waned over up to 96 weeks of further VPA. In two patients ENF added to stable ART had no effect on RCI. Simultaneous intensification with ENF and addition of VPA had no effect on RCI frequency in one patient, and resulted in a 46% decline in a second. No significant depletion of RCI (.50%) was seen in six volunteers after the addition of RAL and VPA. In 4 of the 6 patients this lack of effect might be attributed to intermittent viremia, low VPA levels, or intermittent study therapy adherence. Overall, there was no effect of the addition of RAL or ENF on low-level viremia measured by SCA. Conclusions: The prospective addition of VPA and RAL, VPA and ENF, or ENF failed to progressively reduce the frequency of RCI, or ablate intermittent and low-level viremia. New approaches such as more potent HDAC inhibition, alone or in combination with intensified ART or other agents that may disrupt proviral latency must be pursued

A Self-Supervised Feature Map Augmentation (FMA) Loss and Combined Augmentations Finetuning to Efficiently Improve the Robustness of CNNs

Deep neural networks are often not robust to semantically-irrelevant changes in the input. In this work we address the issue of robustness of state-of-the-art deep convolutional neural networks (CNNs) against commonly occurring distortions in the input such as photometric changes, or the addition of blur and noise. These changes in the input are often accounted for during training in the form of data augmentation. We have two major contributions: First, we propose a new regularization loss called feature-map augmentation (FMA) loss which can be used during finetuning to make a model robust to several distortions in the input. Second, we propose a new combined augmentations (CA) finetuning strategy, that results in a single model that is robust to several augmentation types at the same time in a data-efficient manner. We use the CA strategy to improve an existing state-of-the-art method called stability training (ST). Using CA, on an image classification task with distorted images, we achieve an accuracy improvement of on average 8.94% with FMA and 8.86% with ST absolute on CIFAR-10 and 8.04% with FMA and 8.27% with ST absolute on ImageNet, compared to 1.98% and 2.12%, respectively, with the well known data augmentation method, while keeping the clean baseline performance.Comment: Accepted at ACM CSCS 2020 (8 pages, 4 figures

L-Edge Spectroscopy of Dilute, Radiation-Sensitive Systems Using a Transition-Edge-Sensor Array

We present X-ray absorption spectroscopy and resonant inelastic X-ray scattering (RIXS) measurements on the iron L-edge of 0.5 mM aqueous ferricyanide. These measurements demonstrate the ability of high-throughput transition-edge-sensor (TES) spectrometers to access the rich soft X-ray (100-2000eV) spectroscopy regime for dilute and radiation-sensitive samples. Our low-concentration data are in agreement with high-concentration measurements recorded by conventional grating-based spectrometers. These results show that soft X-ray RIXS spectroscopy acquired by high-throughput TES spectrometers can be used to study the local electronic structure of dilute metal-centered complexes relevant to biology, chemistry and catalysis. In particular, TES spectrometers have a unique ability to characterize frozen solutions of radiation- and temperature-sensitive samples.Comment: 19 pages, 4 figure

Discovery and Validation of Kepler-452b: A 1.6-Re Super Earth Exoplanet in the Habitable Zone of a G2 Star

We report on the discovery and validation of Kepler-452b, a transiting planet identified by a search through the 4 years of data collected by NASA's Kepler Mission. This possibly rocky 1.63$^{+0.23}_{-0.20}$ R$_\oplus$ planet orbits its G2 host star every 384.843$^{+0.007}_{0.012}$ days, the longest orbital period for a small (R$_p$ < 2 R$_\oplus$) transiting exoplanet to date. The likelihood that this planet has a rocky composition lies between 49% and 62%. The star has an effective temperature of 5757$\pm$85 K and a log g of 4.32$\pm$0.09. At a mean orbital separation of 1.046$^{+0.019}_{-0.015}$ AU, this small planet is well within the optimistic habitable zone of its star (recent Venus/early Mars), experiencing only 10% more flux than Earth receives from the Sun today, and slightly outside the conservative habitable zone (runaway greenhouse/maximum greenhouse). The star is slightly larger and older than the Sun, with a present radius of 1.11$^{+0.15}_{-0.09}$ R$_\odot$ and an estimated age of 6 Gyr. Thus, Kepler-452b has likely always been in the habitable zone and should remain there for another 3 Gyr.Comment: 19 pages, 16 figure

Performance characteristics of the Cavidi ExaVir viral load assay and the ultra-sensitive P24 assay relative to the Roche Monitor HIV-1 RNA assay

The Cavidi viral load assay and the ultra-sensitive p24 antigen assay (Up24 Ag) have been suggested as more feasible alternatives to PCR-based HIV viral load assays for use in monitoring patients infected with HIV-1 in resource-limited settings

Planetary Candidates Observed by Kepler V: Planet Sample from Q1-Q12 (36 Months)

The Kepler mission discovered 2842 exoplanet candidates with 2 years of data. We provide updates to the Kepler planet candidate sample based upon 3 years (Q1-Q12) of data. Through a series of tests to exclude false-positives, primarily caused by eclipsing binary stars and instrumental systematics, 855 additional planetary candidates have been discovered, bringing the total number known to 3697. We provide revised transit parameters and accompanying posterior distributions based on a Markov Chain Monte Carlo algorithm for the cumulative catalogue of Kepler Objects of Interest. There are now 130 candidates in the cumulative catalogue that receive less than twice the flux the Earth receives and more than 1100 have a radius less than 1.5 Rearth. There are now a dozen candidates meeting both criteria, roughly doubling the number of candidate Earth analogs. A majority of planetary candidates have a high probability of being bonafide planets, however, there are populations of likely false-positives. We discuss and suggest additional cuts that can be easily applied to the catalogue to produce a set of planetary candidates with good fidelity. The full catalogue is publicly available at the NASA Exoplanet Archive.Comment: Accepted for publication, ApJ