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At least 523 records · Page 29

HIV drug resistance during antiretroviral therapy scale-up in Uganda, 2012–19: a population-based, longitudinal study

Background With scale-up of antiretroviral therapy (ART) in sub-Saharan Africa, increasing pretreatment HIV drug resistance has been reported; however, the broader effect of ART expansion on population-level resistance patterns remains insufficiently quantified. We aimed to estimate the longitudinal prevalence of drug resistance and resistance-conferring mutations. Methods This study used data collected as part of the Rakai Community Cohort Study (RCCS), an open population-based census and cohort study conducted in southern Uganda. At each survey round, residents aged 15–49 years are invited to participate and receive a structured questionnaire that obtains sociodemographic, behavioural, and health information, including self-reported past and current ART use. Voluntary HIV testing is conducted using a rapid test algorithm and a venous blood sample. People with HIV provide samples for viral load quantification and deep sequencing. We analysed RCCS survey, HIV viral load, and deep sequencing (which was used to predict resistance) data from five survey rounds. The key outcomes were the population prevalence of viraemic people with HIV with non-nucleoside reverse transcriptase inhibitor (NNRTI), nucleoside reverse transcriptase inhibitor (NRTI), protease inhibitor, or multiclass resistance among all participants (regardless of HIV serostatus) in the 2015 and 2017 surveys. Prevalence of class-specific resistance and resistance-conferring substitutions were estimated using robust log-Poisson regression. Findings Between Aug 10, 2011, and Nov 4, 2020, there were 43 361 participants in the RCCS and 7923 (18·27%) people with HIV. Over five survey rounds, 93 622 participant visits occurred, among which 17 460 (18·65%) were from people with HIV. Over the analysis period, the median age of study participants remained similar (28 years [22–35] in 2012 and 29 years [21–38] in 2019). Sufficient data were available to reliably genotype 4072 (90·03%) of 4523 participant visits from 3407 people with HIV for at least one drug. Overall population prevalence of resistance contributed by viraemic pretreatment people with HIV decreased between 2012 and 2017 from 0·56% (95% CI 0·42–0·75) to 0·25% (0·18–0·33) for NNRTI and from 0·24% (0·15–0·37) to 0·05% (0·02–0·10) for NRTI (prevalence ratio 0·44 [0·29–0·68] for NNRTI and 0·21 [0·09–0·47] for NRTI). Between 2012 and 2017, NNRTI resistance among viraemic pretreatment people with HIV increased from 4·86% (3·69–6·42) to 9·61% (7·27–12·7; prevalence ratio 1·98 [1·34–2·91]). The prevalence of NNRTI and NRTI resistance was substantially higher among viraemic treatment-experienced people with HIV (51·49% [46·24–57·34] for NNRTI and 36·46% [30·06–44·22] for NRTI in 2017) than among pretreatment people with HIV. NNRTI and NRTI resistance was predominantly attributable to rtK103N and rtM184V. inT97A was observed at a similar prevalence among viraemic treatment-experienced (9·96% [6·41–15·48]) and viraemic pretreatment (10·56% [8·01–13·93]) people with HIV; no major dolutegravir resistance mutations were observed. Interpretation Despite rising NNRTI resistance among pretreatment people with HIV, overall population prevalence of pretreatment HIV drug-resistant viraemia decreased due to increasing ART uptake and viral suppression. This finding underscores the crucial role of achieving and maintaining high ART coverage in reducing transmission of drug-resistant HIV. The high prevalence of mutations conferring resistance to components of first-line ART regimens among viraemic people with HIV is potentially concerning. Funding National Institutes of Health, Johns Hopkins University Center for AIDS Research, Bill & Melinda Gates Foundation, and the US Centers for Disease Control and Prevention.

59 BASIC BIOLOGICAL SCIENCES↗

Using Ada: The deeper challenges

The Ada programming language and the associated Ada Programming Support Environment (APSE) and Ada Run Time Environment (ARTE) provide the potential for significant life-cycle cost reductions in computer software development and maintenance activities. The Ada programming language itself is standardized, trademarked, and controlled via formal validation procedures. Though compilers are not yet production-ready as most would desire, the technology for constructing them is sufficiently well known and understood that time and money should suffice to correct current deficiencies. The APSE and ARTE are, on the other hand, significantly newer issues within most software development and maintenance efforts. Currently, APSE and ARTE are highly dependent on differing implementer concepts, strategies, and market objectives. Complex and sophisticated mission-critical computing systems require the use of a complete Ada-based capability, not just the programming language itself; yet the range of APSE and ARTE features which must actually be utilized can vary significantly from one system to another. As a consequence, the need to understand, objectively evaluate, and select differing APSE and ARTE capabilities and features is critical to the effective use of Ada and the life-cycle efficiencies it is intended to promote. It is the selection, collection, and understanding of APSE and ARTE which provide the deeper challenges of using Ada for real-life mission-critical computing systems. Some of the current issues which must be clarified, often on a case-by-case basis, in order to successfully realize the full capabilities of Ada are discussed.

Feinberg, David A.↗

Techniques and implementation of the embedded rule-based expert system using Ada

Ada is becoming an increasingly popular programming language for large Government-funded software projects. Ada with its portability, transportability, and maintainability lends itself well to today's complex programming environment. In addition, expert systems have also assured a growing role in providing human-like reasoning capability and expertise for computer systems. The integration of expert system technology with Ada programming language, specifically a rule-based expert system using an ART-Ada (Automated Reasoning Tool for Ada) system shell is discussed. The NASA Lewis Research Center was chosen as a beta test site for ART-Ada. The test was conducted by implementing the existing Autonomous Power EXpert System (APEX), a Lisp-base power expert system, in ART-Ada. Three components, the rule-based expert system, a graphics user interface, and communications software make up SMART-Ada (Systems fault Management with ART-Ada). The main objective, to conduct a beta test on the ART-Ada rule-based expert system shell, was achieved. The system is operational. New Ada tools will assist in future successful projects. ART-Ada is one such tool and is a viable alternative to the straight Ada code when an application requires a rule-based or knowledge-based approach.

Liberman, Eugene M.↗

Capability 9.4 Servicing

This paper presents viewgraphs on capability structure 9.4 servicing. The topics include: 1) Servicing Description; 2) Benefits of Servicing; 3) Drivers & Assumptions for Servicing; 4) Capability Breakdown Structure 9.4 Servicing; 5) Roadmap for Servicing; 6) 9.4 Servicing Critical Gaps; 7) Capability 9.4 Servicing; 8) Capability 9.4.1 Inspection; 9) State-of-the-Art /Maturity Level /Capabilities for 9.4.1 Inspection; 10) Capability 9.4.2 Diagnostics; 11) State-of-the-Art/Maturity Level /Capabilities for 9.4.2 Diagnostics; 12) Capability 9.4.3 Perform Planned Maintenance; 13) State-of-the-Art /Maturity Level /Capabilities for 9.4.3 Perform Planned Maintenance; 14) Capability 9.4.4 Perform Unplanned Repair; 15) State-of-the-Art /Maturity Level /Capabilities for 9.4.4 Perform Unplanned Repair; 16) Capability 9.4.5 Install Upgrade; 17) Capability 9.4.5 Install Upgrade; 18) State-of-the-Art /Maturity Level /Capabilities for 9.4.5 Install Upgrade; 19) Capability 9.4.6 Planning, Logistics, Training; and 20) State-of-the-Art /Maturity Level /Capabilities for 9.4.6 Planning, Logistics, & Training;

Moe, Rud↗

System Engineering Paper

The Iowa State University team, Team LunaCY, is composed of the following sub-teams: the main student organization, the Lunabotics Club; a senior mechanical engineering design course, ME 415; a senior multidisciplinary design course, ENGR 466; and a senior design course from Wartburg College in Waverly, Iowa. Team LunaCY designed and fabricated ART-E III, Astra Robotic Tractor- Excavator the Third, for the team's third appearance in the NASA Lunabotic Mining competition. While designing ART-E III, the team had four main goals for this year's competition:to reduce the total weight of the robot, to increase the amount of regolith simulant mined, to reduce dust, and to make ART-E III autonomous. After many designs and research, a final robot design was chosen that obtained all four goals of Team LunaCY. A few changes Team LunaCY made this year was to go to the electrical, computer, and software engineering club fest at Iowa State University to recruit engineering students to accomplish the task of making ART-E III autonomous. Team LunaCY chose to use LabView to program the robot and various sensors were installed to measure the distance between the robot and the surroundings to allow ART-E III to maneuver autonomously. Team LunaCY also built a testing arena to test prototypes and ART-E III in. To best replicate the competition arena at the Kennedy Space Center, a regolith simulant was made from sand, QuickCrete, and fly ash to cover the floor of the arena. Team LunaCY also installed fans to allow ventilation in the arena and used proper safety attire when working in the arena . With the additional practice in the testing arena and innovative robot design, Team LunaCY expects to make a strong appearance at the 2012 NASA Lunabotic Mining Competition. .

Heise, James↗

Lightweight nickel electrodes for nickel/hydrogen cells

Thick nickel electrodes with lightweight substrate material have been prepared and tested in Ni/H2 boilerplate cells containing 26 percent KOH electrolyte. Lightweight substrates used were either 85 or 90 percent in porosity and either 0.8 or 2 mm in thickness, respectively, compared with 80 to 82 percent porosity and 0.75 to 0.8 mm thickness of the state-of-the-art sintered plaque substrate. All of these thick electrodes had substantially improved theoretical (or chemical) capacity over that of state-of-the-art sintered nickel plaque electrodes. However, utilization of the active material was low (65 to 80 percent) compared with that of the state-of-the-art electrodes (approximately 90 percent) in 26 percent KOH. Due to this low utilization, the electrodes using 85 percent porous substrates did not show any advantage over the state-of-the-art ones. The electrodes using a 90 percent porous substrate, however, showed 17 percent higher usable specific capacity (about 0.13 Ah/g in 26 percent KOH) than that of the state-of-the-art nickel electrodes despite the low utilization. These electrodes achieved up to 4860 cycles at 40 percent depth-of-discharge with neither capacity loss nor any significant changes of rate capability and charging efficiency with cycling.

Lim, Hong S.↗

ART/Ada and CLIPS/Ada

Although they have reached a point of commercial viability, expert systems were originally developed in artificial intelligence (AI) research environments. Many of the available tools still work best in such environments. These environments typically utilize special hardware such as LISP machines and relatively unfamiliar languages such as LISP or Prolog. Space Station applications will require deep integration of expert system technology with applications developed in conventional languages, specifically Ada. The ability to apply automation to Space Station functions could be greatly enhanced by widespread availability of state-of-the-art expert system tools based on Ada. Although there have been some efforts to examine the use of Ada for AI applications, there are few, if any, existing products which provide state-of-the-art AI capabilities in an Ada tool. The goal of the ART/Ada Design Project is to conduct research into the implementation in Ada of state-of-the-art hybrid expert systems building tools (ESBT's). This project takes the following approach: using the existing design of the ART-IM ESBT as a starting point, analyze the impact of the Ada language and Ada development methodologies on that design; redesign the system in Ada; and analyze its performance. The research project will attempt to achieve a comprehensive understanding of the potential for embedding expert systems in Ada systems for eventual application in future Space Station Freedom projects. During Phase 1 of the project, initial requirements analysis, design, and implementation of the kernel subset of ART-IM functionality was completed. During Phase 2, the effort has been focused on the implementation and performance analysis of several versions with increasing functionality. Since production quality ART/Ada tools will not be available for a considerable time, and additional subtask of this project will be the completion of an Ada version of the CLIPS expert system shell developed by NASA. This tool will provide full syntactic compatibility with any eventual products of the ART/Ada design while allowing SSFP developers early access to this technology.

Culbert, Chris↗

Software for Simulating Remote Sensing Systems

The Application Research Toolbox (ART) is a collection of computer programs that implement algorithms and mathematical models for simulating remote sensing systems. The ART is intended to be especially useful for performing design-tradeoff studies and statistical analyses to support the rational development of design requirements for multispectral imaging systems. Among other things, the ART affords a capability to synthesize coarser-spatial-resolution image-data sets from finer-spatial-resolution data sets and multispectral-image-data products from hyperspectral-image-data products. The ART also provides for synthesis of image-degradation effects, including point-spread functions, misregistration of spectral images, and noise. The ART can utilize real or synthetic data sets, along with sensor specifications, to create simulated data sets. In one example of a typical application, simulated data pertaining to an existing multispectral sensor system are used to verify the data collected by the system in operation. In the case of a proposed sensor system, the simulated data can be used to conduct trade studies and statistical analyses to ensure that the sensor system will satisfy the requirements of potential scientific, academic, and commercial user communities.

Zanoni, Vicki↗

Software for Simulating Remote Sensing Systems

The Application Research Toolbox (ART) is a collection of computer programs that implement algorithms and mathematical models for simulating remote sensing systems. The ART is intended to be especially useful for performing design-tradeoff studies and statistical analyses to support the rational development of design requirements for multispectral imaging systems. Among other things, the ART affords a capability to synthesize coarser-spatial-resolution image-data sets from finer-spatial-resolution data sets and multispectral-image-data products from hyperspectral-image-data products. The ART also provides for synthesis of image-degradation effects, including point-spread functions, misregistration of spectral images, and noise. The ART can utilize real or synthetic data sets, along with sensor specifications, to create simulated data sets. In one example of a typical application, simulated data pertaining to an existing multispectral sensor system are used to verify the data collected by the system in operation. In the case of a proposed sensor system, the simulated data can be used to conduct trade studies and statistical analyses to ensure that the sensor system will satisfy the requirements of potential scientific, academic, and commercial user communities.

Vicki Zanoni↗

Carbon-Nanotube Schottky Diodes

Schottky diodes based on semiconducting single-walled carbon nanotubes are being developed as essential components of the next generation of submillimeter-wave sensors and sources. Initial performance predictions have shown that the performance characteristics of these devices can exceed those of the state-of-the-art solid-state Schottky diodes that have been the components of choice for room-temperature submillimeter-wave sensors for more than 50 years. For state-of-the-art Schottky diodes used as detectors at frequencies above a few hundred gigahertz, the inherent parasitic capacitances associated with their semiconductor junction areas and the resistances associated with low electron mobilities limit achievable sensitivity. The performance of such a detector falls off approximately exponentially with frequency above 500 GHz. Moreover, when used as frequency multipliers for generating signals, state-of-the-art solid-state Schottky diodes exhibit extremely low efficiencies, generally putting out only micro-watts of power at frequencies up to 1.5 THz. The shortcomings of the state-of-the-art solid-state Schottky diodes can be overcome by exploiting the unique electronic properties of semiconducting carbon nanotubes. A single-walled carbon nanotube can be metallic or semiconducting, depending on its chirality, and exhibits high electron mobility (recently reported to be approx.= 2x10(exp 5)sq cm/V-s) and low parasitic capacitance. Because of the narrowness of nanotubes, Schottky diodes based on carbon nanotubes have ultra-small junction areas (of the order of a few square nanometers) and consequent junction capacitances of the order of 10(exp -18) F, which translates to cutoff frequency >5 THz. Because the turn-on power levels of these devices are very low (of the order of nano-watts), the input power levels needed for pumping local oscillators containing these devices should be lower than those needed for local oscillators containing state-of-the-art solid-state Schottky diodes.

Manohara, Harish↗

Simulating Remote Sensing Systems

The Application Research Toolbox (ART) is a collection of computer programs that implement algorithms and mathematical models for simulating remote sensing systems. The ART is intended to be especially useful for performing design-tradeoff studies and statistical analyses to support the rational development of design requirements for multispectral imaging systems. Among other things, the ART affords a capability to synthesize coarser-spatial-resolution image-data products. The ART also provides for simulations of image-degradation effects, including point-spread functions, misregistration of spectral images, and noise. The ART can utilize real or synthetic data sets, along with sensor specifications, to create simulated data sets. In one example of a particular application, simulated imagery of a coarse resolution system was created using high-resolution imagery from another system in order to perform a radiometric cross-comparison. In the case of a proposed sensor system, the simulated data can be used to conduct trade studies and statistical analyses to ensure that the sensor system will satisfy the requirements of potential scientific, academic, and commercial user communities.

Zanoni, Vicki↗

An Astro-Animation Class: Optimizing Artistic, Educational and Outreach Outcomes

The authors investigate how teaching art and astronomy together has the potential to inspire new art forms, enhance scientific public outreach, and promote art and science education. The authors teach an astro-animation class at the Maryland Institute College of Art in partnership with NASA scientists. The animations explore science in creative ways. Astrophysicists, educators, students, and the general public were surveyed to evaluate the experiences, and benefits from this project. The responses were very positive -the program is an effective way to stimulate art students to learn science, share an artist’s viewpoint beyond the classroom, and engage with the public.

Animation↗

Overview of NASA's Solar Electric Propulsion Project

NASA is continuing to develop and qualify a state of the art 13 kW-class Advanced Electric Propulsion System (AEPS) for NASA exploration missions through a contract with Aerojet Rocketdyne. An objective of the AEPS project is to empower the US space industry to accelerate the adoption of high power electric propulsion technologies by reducing the risk and uncertainty of integrating Solar Electric Propulsion (SEP) technologies into space flight systems. NASA and AEPS contract has recently initiated engineering hardware testing of the Hall Current Thruster (HCT), Power Processing Unit (PPU), and Xenon Flow Controller (XFC) at both the component and system levels. The successful completion of these tests will provide the required information to advance the AEPS system towards Critical Design Review. In support of the AEPS contract, NASA and JPL have been performing risk reduction activities to address specific concerns of the state of the art higher power Hall thruster propulsion system. These risk reduction activities have included long duration wear testing of the Technology Demonstration Unit (TDU) Hall thruster and cathode hardware, thermal cycling testing of TDU cathode heaters and coils, plasma plume measurements, and investigating PPU design. In addition to NASA propulsion development, the SEP project is developing the Plasma Diagnostic Package (PDP) and the SEP Testbed. The PDP is designed for use in conjunction with a high powered EP system to characterize in-space operation. The SEP Testbed system is developed for demonstration of Abstract: NASA is continuing to develop and qualify a state of the art 13 kW-class Advanced Electric Propulsion System (AEPS) for NASA exploration missions through a contract with Aerojet Rocketdyne. An objective of the AEPS project is to empower the US space industry to accelerate the adoption of high power electric propulsion technologies by reducing the risk and uncertainty of integrating Solar Electric Propulsion (SEP) technologies into space flight systems. NASA and AEPS contract has recently initiated engineering hardware testing of the Hall Current Thruster (HCT), Power Processing Unit (PPU), and Xenon Flow Controller (XFC) at both the component and system levels. The successful completion of these tests will provide the required information to advance the AEPS system towards Critical Design Review. In support of the AEPS contract, NASA and JPL have been performing risk reduction activities to address specific concerns of the state of the art higher power Hall thruster propulsion system. These risk reduction activities have included long duration wear testing of the Technology Demonstration Unit (TDU) Hall thruster and cathode hardware, thermal cycling testing of TDU cathode heaters and coils, plasma plume measurements, and investigating PPU design. In addition to NASA propulsion development, the SEP project is developing the Plasma Diagnostic Package (PDP) and the SEP Testbed. The PDP is designed for use in conjunction with a high powered EP system to characterize in-space operation. The SEP Testbed system is developed for demonstration of an integrated SEP end-to-end system performance. The paper will present an overview of the NASA and the AEPS contract activities and a summary of the associated NASA in-house activities.

Plasma Diagnostics Package↗

Provable Repair of Vision Transformers

Vision Transformers have emerged as state-of-the-art image recognition tools, but may still exhibit incorrect behavior. Incorrect image recognition can have disastrous consequences in safety-critical real-world applications such as self-driving automobiles. In this paper, we present Provable Repair of Vision Transformers (PRoViT), a provable repair approach that guarantees the correct classification of images in a repair set for a given Vision Transformer without modifying its architecture. PRoViT avoids negatively affecting correctly classified images (drawdown) by minimizing the changes made to the Vision Transformer’s parameters and original output. Here, we observe that for Vision Transformers, unlike for other architectures such as ResNet or VGG, editing just the parameters in the last layer achieves correctness guarantees and very low drawdown. We introduce a novel method for editing these last-layer parameters that enables PRoViT to efficiently repair state-of-the-art Vision Transformers for thousands of images, far exceeding the capabilities of prior provable repair approaches.

97 MATHEMATICS AND COMPUTING↗

Dual blockade of IL-10 and PD-1 leads to control of SIV viral rebound following analytical treatment interruption

Human immunodeficiency virus (HIV) persistence during antiretroviral therapy (ART) is associated with heightened plasma interleukin-10 (IL-10) levels and PD-1 expression. We hypothesized that IL-10 and PD-1 blockade would lead to control of viral rebound following analytical treatment interruption (ATI). Twenty-eight ART-treated, simian immunodeficiency virus (SIV)mac 239 -infected rhesus macaques (RMs) were treated with anti-IL-10, anti-IL-10 plus anti-PD-1 (combo) or vehicle. ART was interrupted 12 weeks after introduction of immunotherapy. Durable control of viral rebound was observed in nine out of ten combo-treated RMs for >24 weeks post-ATI. Induction of inflammatory cytokines, proliferation of effector CD8 + T cells in lymph nodes and reduced expression of BCL-2 in CD4 + T cells pre-ATI predicted control of viral rebound. Twenty-four weeks post-ATI, lower viral load was associated with higher frequencies of memory T cells expressing TCF-1 and of SIV-specific CD4 + and CD8 + T cells in blood and lymph nodes of combo-treated RMs. These results map a path to achieve long-lasting control of HIV and/or SIV following discontinuation of ART.

60 APPLIED LIFE SCIENCES↗

Identifying a next-generation antimalarial trioxolane in a landscape of artemisinin partial resistance

For over two decades, artemisinin-based combination therapy (ACT) has been the standard of care for the treatment of uncomplicated falciparum malaria. However, artemisinin partial resistance (ART-R) is now prevalent in Southeast Asia and has emerged in eastern Africa, threatening ACT efficacy. Artefenomel, a synthetic 1,2,4-trioxolane, exhibits an extended pharmacokinetic exposure profile that predicts for efficacy against ART-R parasites. Unfortunately, the development of artefenomel was halted recently after almost a decade in the clinic. Here, we describe studies of an artefenomel-adjacent chemotype that combines potent in vitro activity against clinical ART-R parasites, an extended pharmacokinetic profile with single-exposure efficacy in a murine malaria model, and enhanced stability in human microsomes and hepatocytes. Overall, our studies reveal a heretofore underexplored trioxolane chemotype with the potential to address ART-R in a next-generation trioxolane development candidate.

Science & Technology - Other Topics↗

Effect of in utero and lactational exposure to antiretroviral therapy on the gut microbial composition and metabolic function in aged rat offspring

Despite the highly effective impact of antiretroviral therapy (ART) in reducing mother-to-child transmission of human immunodeficiency virus (HIV), there are concerns of long-term impacts of ART on the health of the offspring. The implications of perinatal exposure to antiviral drugs on the gut bacterial population and metabolic function in the offspring is unclear but may influence health outcomes given the various reported effects of the microbiome in human health. This study aims to gain insight into the potential effect ofin uteroand lactational exposure to ART on gut microbiota populations and short‐chain fatty acids (SCFAs) production in aged rat offspring. Pregnant rats were administered a combination of antiretroviral drugs (abacavir/dolutegravir/lamivudine) at two different dose levels during gestation and throughout lactation, and the fecal bacterial abundance and SCFA levels of the offspring were analyzed when they reached 12 months of age. Our results showed dose-dependent and sex-based differences in fecal microbial abundance at various taxonomic levels. Specifically, we found a decline inFirmicutesin males, and an increase inActinobacteriaamong males and females. Furthermore, a sex-specific distribution reorganization ofLactobacillus,Bifidobacterium, andAkkermansiawas identified. No significant difference in the concentration of prominent SCFAs and IgA levels were identified. These findings provide preliminary information indicating the need to evaluate perinatal effects of ART more comprehensively on the gut bacterial and metabolic function in future studies, and their potential role in offspring health outcomes.

Research & Experimental Medicine↗

Thermostructural analysis of three structural concepts for reusable space vehicles

Three structural concepts are studied: (1) a state-of-the-art insulated aluminum skin-stringer structure; (2) a near-art insulated evacuated aluminum-alloy honeycomb structure; and (3) an advanced evacuated Rene 41 honeycomb hot structure. Each is evaluated for its thermostructural performance for each of the flight profiles (ascent, entry, and a recall or abort). Results indicate that (1) the state-of-the-art structure encounters negligible thermal stress; (2) the near-art structure has acceptable thermal stresses; and (3) the advanced structure will have thermal stress levels above the material allowables.

Taylor, A. H.↗