A Menin-MLL Inhibitor Induces Specific Chromatin Changes and Eradicates Disease in Models of MLL-Rea
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Krivtsov, Andrei V.↗
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Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.
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X-ray computed tomography of extraterrestrial rocks eradicates their natural radiation record and the information it contains
Abstract not provided
Sears, Derek W. G.↗
The reductase TMX1 contributes to ERAD by preferentially acting on membrane-associated folding-defective polypeptides
The Endoplasmic Reticulum (ER) is site of production of secretory and membrane proteins in eukaryotic cells. The ER does not contain catabolic devices and misfolded proteins generated in its lumen must be dislocated across the ER membrane before clearance by cytosolic proteasomes (ER-Associated Degradation, ERAD). How misfolded proteins are dislocated across the ER membrane is a matter of controversy. For example, it remains to be established if polypeptide unfolding is always required. If unfolding is a pre-requisite for dislocation as emerging evidences seem to indicate, it is likely that the incorrect set of disulfide bonds established during unsuccessful folding-attempts that precede selection for ERAD must be reduced to eliminate tertiary and quaternary structures that could hamper dislocation. The lumen of the mammalian ER contains more than 20 members of the PDI family, a handful of which plays a role in ERAD. Here we add the atypical, membrane-bound reductase TMX1 to this list and we show that TMX1 preferentially acts on membrane-tethered folding-defective polypeptides essentially ignoring the same misfolded ectodomains, when not associated to the ER membrane. As such, TMX1 is the first example of a topology-specific client protein redox catalyst acting both in the folding and in the degradative pathways.
60 APPLIED LIFE SCIENCES↗
A clue to unprecedented strategy to HIV eradication: “Lock-in and apoptosis”
Despite the development of antiretroviral therapy against HIV, eradication of the virus from the body, as a means to a cure, remains in progress. A “kick and kill” strategy proposes “kick” of the latent HIV to an active HIV to eventually be “killed”. Latency-reverting agents that can perform the “kick” function are under development and have shown promise. Management of the infected cells not to produce virions after the “kick” step is important to this strategy. Here we show that a newly synthesized compound, L-HIPPO, captures the HIV-1 protein Pr55Gag and intercepts its function to translocate the virus from the cytoplasm to the plasma membrane leading to virion budding. The infecting virus thus “locked-in” subsequently induces apoptosis of the host cells. This “lock-in and apoptosis” approach performed by our novel compound in HIV-infected cells provides a means to bridge the gap between the “kick” and “kill” steps of this eradication strategy. By building upon previous progress in latency reverting agents, our compound appears to provide a promising step toward the goal of HIV eradication from the body
60 APPLIED LIFE SCIENCES↗
Powered By ERAD [Slides]
Energy Resilience Analysis for Distribution Power System (ERAD) is a free, open-source Python toolkit for estimating the energy and service impacts of hazards like earthquakes and flooding. It uses a graph-based approach to capture high resolution connectivity among the grid, critical services, and customers and rapidly compute household level metrics and aggregated statistics across large distribution systems. It uses asset fragility curves that relate hazard severity to survival probability for power system equipment including cables, transformers, substations, etc. The tool is designed to be modular and extensible, allowing it to interface with third-party hazard simulators and integrate into broader resilience analysis workflows. ERAD enables researchers, students, communities, distribution utilities, and other stakeholders to understand hazard impacts and evaluate the effectiveness of different programs to improve energy resilience. The webinar was hosted by NLR researcher Aadil Latif.
24 POWER TRANSMISSION AND DISTRIBUTION↗
An overview of the development of remote sensing techniques for the screwworm eradication program
The current status of remote sensing techniques developed for the screwworm eradication program of the Mexican-American Screwworm Eradication Commission was reported. A review of the type of data and equipment used in the program is presented. Future applications of remote sensing techniques are considered.
Barnes, C. M.↗
System development of the Screwworm Eradication Data System (SEDS) algorithm
The use of remotely sensed data is reported in the eradication of the screwworm and in the study of the role of the weather in the activity and development of the screwworm fly. As a result, the Screwworm Eradication Data System (SEDS) algorithm was developed.
Arp, G.↗
ERAD (Energy Resilience Analysis for Electric Distribution Systems) [SWR-22-75]
ERAD is a software product for computing resiliency metrics in power distribution systems. It uses graph database technology to store, query and compute metrics making it highly scalable and available. Metrics can be computed for various resiliency scenarios such as fire, flooding, earthquake.
Palmintier, Bryan↗
ERAD: A Graph-Based Tool for Energy Resilience Analysis of Electric Distribution Systems
Understanding the impact of extreme events on people's ability to access energy is crucial for designing resilient energy systems. In the event of a disaster, damage to the electric system and related infrastructure (e.g., downed power lines, flooded equipment, hacked communication systems, damaged roads, etc.) can impact people's access to critical services, including not just electricity but also shelter, food, healthcare, and more. There is a key need to understand such impacts better and evaluate options to improve energy resilience. The Energy Resilience Analysis for Electric Distribution Systems (ERAD) tool is a free and open-source software package designed to help researchers and decision-makers analyze and improve energy system resilience.
24 POWER TRANSMISSION AND DISTRIBUTION↗
Screwworm Eradication Data System (SEDS) preprocessor program documentation, part 1
To achieve the capability required by the Screwworm Eradication Data System (SEDS) and to process the 14-track analog tapes supplied by the National Oceanic and Atmospheric Administration, the existing Earth Resources Preprocessor Software Subsystem (ERPSS) was enhanced. A brief overview of the ERPSS is given along with descriptions of only those computer program components that were modified to meet the SEDS requirements.
Source record↗
The screwworm eradication data system archives
The archives accumulated during 1 year of operation of the Satellite Temperature-Monitoring System during development of the Screwworm Eradication Data System are reported. Brief descriptions of all the kinds of tapes, as well as their potential uses, are presented. Reference is made to other documents that explain the generation of these data.
Barnes, C. M.↗
A Structurally Unique E2-Binding Domain Activates Ubiquitination by the ERAD E2, Ubc7p, through Multiple Mechanisms
Abstract not provided
Metzger, Meredith B.↗
Monte Carlo modeling and simulation of electron beam irradiation optimization for screwworm fly eradication through sterile insect technique
Not Available
Mulyana, Dany (ORCID:0000000307143306)↗
Alternating magnetic fields and antibiotics eradicate biofilm on metal in a synergistic fashion
Abstract Hundreds of thousands of human implant procedures require surgical revision each year due to infection. Infections are difficult to treat with conventional antibiotics due to the formation of biofilm on the implant surface. We have developed a noninvasive method to eliminate biofilm on metal implants using heat generated by intermittent alternating magnetic fields (iAMF). Here, we demonstrate that heat and antibiotics are synergistic in biofilm elimination. For Pseudomonas aeruginosa biofilm, bacterial burden was reduced >3 log with iAMF and ciprofloxacin after 24 h compared with either treatment alone ( p < 0.0001). This effect was not limited by pathogen or antibiotic as similar biofilm reductions were seen with iAMF and either linezolid or ceftriaxone in Staphylococcus aureus . iAMF and antibiotic efficacy was seen across various iAMF settings, including different iAMF target temperatures, dose durations, and dosing intervals. Initial mechanistic studies revealed membrane disruption as one factor important for AMF enhanced antibacterial activity in the biofilm setting. This study demonstrates the potential of utilizing a noninvasive approach to reduce biofilm off of metallic implants.
59 BASIC BIOLOGICAL SCIENCES↗
Covalent inhibitors for eradication of drug-resistant HIV-1 reverse transcriptase: From design to protein crystallography
Development of resistance remains a major challenge for drugs to treat HIV-1 infections, including those targeting the essential viral polymerase, HIV-1 reverse transcriptase (RT). Resistance associated with the Tyr181Cys mutation in HIV-1 RT has been a key roadblock in the discovery of nonnucleoside RT inhibitors (NNRTIs). It is the principal point mutation that arises from treatment of HIV-infected patients with nevirapine, the first-in-class drug still widely used, especially in developing countries. We report covalent inhibitors of Tyr181Cys RT (CRTIs) that can completely knock out activity of the resistant mutant and of the particularly challenging Lys103Asn/Tyr181Cys variant. Conclusive evidence for the covalent modification of Cys181 is provided from enzyme inhibition kinetics, mass spectrometry, protein crystallography, and antiviral activity in infected human T-cell assays. As a result, the CRTIs are also shown to be selective for Cys181 and have lower cytotoxicity than the approved NNRTI drugs efavirenz and rilpivirine.
59 BASIC BIOLOGICAL SCIENCES↗
The Screwworm Eradication Data System (SEDS)
One of the objectives of the SEDS was to build a versatile, yet economical, interactive system on the existing digital PDP 11/45 computers used in the Skylab production processing system. Previous experience on various interactive systems gave some background in the best methods of handling image data, registering and correcting the data, and extracting useful information from the images. The screwworm was eliminated in many parts of the United States by air-dropping sterile screwworms in areas where screwworms breed. The reproduction of the screwworm can be more or less predicted based on weather conditions -- cold weather slows the breeding, warm weather fosters it, and some moisture appears to enhance breeding conditions which, in turn, improves the chances of screwworm population growth. To obtain temperature and moisture conditions from remote areas, the NOAA improved TIROS operational satellite was selected to give data from the very high resolution radiometer (VHRR). The VHRR is a two-channel scanning instrument sensitive to energy in the visible spectrum from 0.6 to 0.7 micrometers and the infrared spectrum from 10.5 to 12.5 micrometers.
Quinn, M. J.↗
Screwworm Eradication Data System (SEDS) applications program documentation, part 2
National Oceanic and Atmospheric Administration (NOAA) satellite data, which is in analog tape form, is converted into output data products. These products are used by investigators in determining optimum areas for airdrops of steril screwworm flies over Mexico. The output product of SEDS takes the form of imagery data film slides showing Mexico and the lower southwest portion of the United States. The area analog preprocessing phase of the SEDS task is covered.
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