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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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At least 19 records
All sourcesNASA NTRSDOE OSTI
DOE OSTI2018

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↗
DOE OSTI2017

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↗
DOE OSTI2026

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↗
DOE OSTI2025

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↗
DOE OSTI2021

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↗
DOE OSTI2017

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↗
DOE OSTI2017

How can we eradicate chlamydia?

Chlamydia is the most commonly contracted STI and affects millions of people worldwide, but it's not just hurting humans--it's also decimating koala populations! Find out how researches at the Lab are working toward developing the first vaccine against chlamydia--good news for humans and koalas.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2017

The Arabidopsis endoplasmic reticulum associated degradation pathways are involved in the regulation of heat stress response

Abstracts: The Cytosolic Protein Response (CPR) in the cytosol and the Unfolded Protein Response (UPR) and ER-associated degradation (ERAD) in the endoplasmic reticulum are major pathways of the cellular proteostasis network. However, despite years of effort, how these protein quality control systems coordinated in vivo remains largely unknown, particularly in plants. In this study, the roles of two evolutionarily conserved ERAD pathways (DOA10 and HRD1) in heat stress response were investigated through reverse genetic approaches in Arabidopsis. Phenotypic analysis of the mutants showed that the two ERAD pathways additively play negative roles in heat tolerance, which was demonstrated by higher survival rate and lower electrolyte leakage in the loss of function mutants compared to the wild type plants. Importantly, gene expression analysis revealed that the mutant plants showed elevated transcriptional regulation of several downstream genes, including those encoding CPR and UPR marker genes, under both basal and heat stress conditions. Finally, multiple components of ERAD genes exhibited rapid response to increasing temperature. Taken together, our data not only unravels key insights into the crosstalk between different protein quality control processes, but also provides candidate genes to genetically improve plant heat tolerance in the future. - Highlights: • ERAD pathways cooperatively regulate plant thermotolerance. • ERAD pathways cooperatively regulate UPR and CPR. • ERAD components gene expression are upregulated by heat stress.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2019

What Constitutes Optimal Management of T1N0 Esophageal Adenocarcinoma?

Purpose and Design: Esophageal adenocarcinoma (EAC) develops as a consequence of gastroesophageal reflux disease and Barrett’s esophagus (BE). While combination therapy with chemotherapy or concurrent chemoradiotherapy followed by esophagectomy improves survival in more advanced tumors, the optimal treatment strategy for early-stage EAC is undefined. Endoscopic eradication therapy, consisting of endoscopic resection and mucosal ablation, has revolutionized therapy for superficial (T1a) EAC in BE and allows for esophageal preservation in appropriate patients at low risk for lymph node metastasis (LNM). This review critically examines the literature regarding evaluation, treatment, and outcomes in patients with T1 EAC. Methods: The literature was queried via the PubMed database to include articles published between 1990 and 2017. Search terms were generated from the key statements “Endoscopic eradication therapy results in equivalent overall survival when compared to esophagectomy for clinical T1aN0 EAC” and “Esophagectomy provides better overall survival than endoscopic eradication therapy for cT1b EAC”. Abstracts were reviewed and included according to predefined selection and exclusion criteria, and were then assessed according to the GRADE system. Results and Conclusions: In patients with T1aN0 EAC, overall survival with endoscopic eradication therapy is equal to esophagectomy. Given the substantial risk of LNM in patients with submucosal (T1b) EAC, esophagectomy remains the standard of care for surgical candidates. In the case of inoperability or low-risk lesions, endoscopic resection may be considered adequate therapy. Chemotherapy and radiation can be offered as primary therapy for non-surgical candidates with lesions not amenable to endoscopic therapy, but does not have a clear role in the adjuvant setting after either endoscopic or surgical resection.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2016

Autocrine Semaphorin3A signaling is essential for the maintenance of stem-like cells in lung cancer

Cancer stem-like cells (CSCs) exist in tumor tissues composed of heterogeneous cell population and are characterized by their self-renewal capacity and tumorigenicity. Many studies demonstrate that eradication of CSCs prevents development and recurrences of tumor; yet, molecules critical for the maintenance of CSCs have not been completely understood. We previously reported that Semaphorin3A (Sema3a) knockdown suppressed the tumorigenicity and proliferative capacity of Lewis lung carcinoma (LLC) cells. Therefore, we identified Sema3a as an essential factor for the establishment or maintenance of CSCs derived from LLC (LLC-stem cell). shRNA against Sema3a was introduced into LLC cells to establish a LLC-stem cell line and its effects on tumorigenesis, sphere formation, and mTORC1 activity were tested. Sema3a knockdown completely abolished tumorigenicity and the sphere-formation and self-renewal ability of LLC-stem cells. The Sema3a knockdown was also associated with decreased expression of mRNA for stem cell markers. The self-renewal ability abolished by Sema3a knockdown could not be recovered by exogenous addition of recombinant SEMA3A. In addition, the activity of mammalian target of rapamycin complex 1 (mTORC1) and the expression of its substrate p70S6K1 were also decreased. These results demonstrate that Sema3a is a potential therapeutic target in eradication of CSCs. - Highlights: • Sema3a enhances tumorigenic capacity of cancer stem-like cells. • Sema3a is essential for the maintenance of cancer stem-like cells. • Sema3a can be a therapeutic target to eradicate cancer stem-like cells.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2017

Balloon-Occluded Retrograde Transvenous Obliteration of a Gastric Vascular Malformation: An Innovative Approach to Treatment of a Rare Condition

Arteriovenous malformations (AVMs) are a high-flow form of a vascular malformation, which can be found anywhere in the body. While historically treated surgically, a multidisciplinary approach utilizing multiple specialties and treatment modalities is now commonly employed. In order to effectively treat an AVM, the nidus must be targeted and eradicated, which can be done via multiple approaches. We present the case of a 43-year-old male with a gastric wall AVM, which was initially incompletely treated using a percutaneous transarterial approach. The gastric AVM was noted to have dominant drainage through a gastrorenal shunt; therefore, Balloon-occluded Retrograde Transvenous Obliteration (BRTO) was utilized to eradicate the AVM nidus. This case illustrates the utility of Interventional Radiology, specifically BRTO, as another treatment option for challenging AVMs.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2016

Brown tree snake ( Boiga irregularis ) population density and carcass locations following exposure to acetaminophen

Mass aerial delivery of dead mouse baits treated with acetaminophen has been evaluated as a means to reduce brown treesnake (Boiga irregularis) populations over large areas, increasing the likelihood of wide-scale eradication on Guam. Given the high density of snakes in some areas of their invasive range, eradication efforts could result in a resource pulse that may influence food web dynamics and the indirect transport of acetaminophen among trophic levels. In this study, we evaluated abundance, habitat type, and snake size (i.e., age) within two study sites on Guam, a secondary limestone forest (upland) and an abandoned coconut plantation (coastal), to determine how experimentally dosing snakes with acetaminophen is likely to influence carrion availability. We found snakes trapped in 3.24 ha plots occurred in greater abundance (population size = 72.5 snakes; SE = 8.8) and were significantly larger (978.6 mm, SE = 14.9) in the coastal than in the upland site (population size = 26.9, SE = 21.5; length = 903.0 mm, SE = 15.9). Despite these differences, carcasses of snakes that died after consuming acetaminophen-laced mice (80 mg) were recovered in consistent locations between sites, with 92% located on the ground, 4% in trees, and 4% found in rock cavities at both sites. Given that most snakes died on the ground rather than in the tree canopy, our results suggest that many poisoned snake carcasses will be accessible to a wide range of potential scavengers, possibly influencing food web dynamics and potentially contributing to indirect toxicant transfer within affected ecosystems.

59 BASIC BIOLOGICAL SCIENCES↗