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Results for “Efficacy”
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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Efficacy of the Method of Four Coefficients to Determine Charge-Carrier Scattering
The investigation of the electronic properties of semiconductors from transport measurements (i.e., resistivity, Hall, and Seebeck coefficient measurements) is challenging due to the averaging of charge-carrier dynamics inherent in such measurements. Here, we investigate the incorporation of a fourth measurement of electronic transport, the Nernst coefficient, into the analysis, termed the method of four coefficients. This approach yields the Fermi level, effective mass, scattering exponent, and relaxation time prefactor. We begin with a review of the underlying mathematics and investigate the mapping between the four-dimensional material property and transport coefficient spaces. We then investigate how the traditional single-parabolic band method yields a single, potentially incorrect point on the solution subspace. This uncertainty can be resolved through Nernst coefficient measurements and we map the span of the ensuing subspace. We conclude with an investigation of how sensitive the analysis of transport coefficients is to experimental error for different sample types.
Efficacy of information transmission in cellular communication
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On The Role of Prompt Construction In Enhancing Efficacy and Efficiency of LLM-Based Tabular Data Generation
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Experiments to Quantify the Shielding Efficacy of Materials to be Implemented for Portable Shielding Enclosures that Adequately Mitigate EMI from Lighting Attachment Events
Mitigating electric and magnetic fields induced by lightning strike events is critical for the security and longevity of electrical components. Electromagnetic interference originating from a lightning strike is categorized into the low to medium frequency ranges, commonly referred to as the “magnetic coupling” regime. This low-frequency characteristic brings about the problem of shielding magnetic flux lines. Such shielding can be accomplished with highly conductive materials via the generation of eddy currents or by diverting the flux lines using materials with a large relative permeability. The shielding effectiveness of materials with varying thicknesses and geometry are tested using a pulse forming network having comparable characteristics to a scaled lighting strike. A four-stage Marx generator with a peak current of ~33 kA and a risetime of 1.4 μs is used as the pulse forming network to emulate the scaled electric and magnetic fields. The data collected from these experiments provide information and techniques that can be implemented into the design of a portable, deployable shielding enclosure.
Efficacy of Spatial and Temporal RHBD Techniques at Advanced Bulk FinFET Technology Nodes
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Rutin is a potent senomorphic agent to target senescent cells and can improve chemotherapeutic efficacy
Aging is a major risk factor for most chronic disorders, for which cellular senescence is one of the central hallmarks. Senescent cells develop the pro-inflammatory senescence-associated secretory phenotype (SASP), which significantly contributes to organismal aging and age-related disorders. Development of senotherapeutics, an emerging class of therapeutic agents to target senescent cells, allows to effectively delay aging and alleviate chronic pathologies. Here we report preliminary outputs from screening of a natural medicinal agent (NMA) library for senotherapeutic candidates and validated several agents with prominent potential as senomorphics. Rutin, a phytochemical constituent found in a number of plants, showed remarkable capacity in targeting senescent cells by dampening expression of the full spectrum SASP. Further analysis indicated that rutin restrains the acute stress-associated phenotype (ASAP) by specifically interfering with the interactions of ATM with HIF1α, a master regulator of cellular and systemic homeostasis activated during senescence, and of ATM with TRAF6, part of a key signaling axis supporting the ASAP development toward the SASP. Conditioned media produced by senescent stromal cells enhanced the malignant phenotypes of prostate cancer cells, including in vitro proliferation, migration, invasion, and more importantly, chemoresistance, while rutin remarkably downregulated these gain-of-functions. Although classic chemotherapy reduced tumor progression, the treatment outcome was substantially improved upon combination of a chemotherapeutic agent with rutin. Our study provides a proof of concept for rutin as an emerging natural senomorphic agent, and presents an effective therapeutic avenue for alleviating age-related pathologies including cancer.
High efficacy of layered controls for reducing exposure to airborne pathogens
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Plant‐produced SARS ‐ CoV ‐2 antibody engineered towards enhanced potency and in vivo efficacy
Summary Prevention of severe COVID‐19 disease by SARS‐CoV‐2 in high‐risk patients, such as immuno‐compromised individuals, can be achieved by administration of antibody prophylaxis, but producing antibodies can be costly. Plant expression platforms allow substantial lower production costs compared to traditional bio‐manufacturing platforms depending on mammalian cells in bioreactors. In this study, we describe the expression, production and purification of the originally human COVA2‐15 antibody in plants. Our plant‐produced mAbs demonstrated comparable neutralizing activity with COVA2‐15 produced in mammalian cells. Furthermore, they exhibited similar capacity to prevent SARS‐CoV‐2 infection in a hamster model. To further enhance these biosimilars, we performed three glyco‐ and protein engineering techniques. First, to increase antibody half‐life, we introduced YTE‐mutation in the Fc tail; second, optimization ofN‐linked glycosylation by the addition of a C‐terminal ER‐retention motif (HDEL), and finally; production of mAb in plant production lines lacking β‐1,2‐xylosyltransferase and α‐1,3‐fucosyltransferase activities (FX‐KO). These engineered biosimilars exhibited optimized glycosylation, enhanced phagocytosis and NK cell activation capacity compared to conventional plant‐produced S15 and M15 biosimilars, in some cases outperforming mammalian cell produced COVA2‐15. These engineered antibodies hold great potential for enhancingin vivoefficacy of mAb treatment against COVID‐19 and provide a platform for the development of antibodies against other emerging viruses in a cost‐effective manner.
Efficacy of Lacosamide and Rufinamide as Adjuncts to Midazolam-Ketamine Treatment Against Cholinergic-Induced Status Epilepticus in Rats
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Soil organic matter attenuates the efficacy of flavonoid-based plant-microbe communication
Plant-microbe interactions are mediated by signaling compounds that control vital plant functions, such as nodulation, defense, and allelopathy. While interruption of signaling is typically attributed to biological processes, potential abiotic controls remain less studied. Here, we show that higher organic carbon (OC) contents in soils repress flavonoid signals by up to 70%. Furthermore, the magnitude of repression is differentially dependent on the chemical structure of the signaling molecule, the availability of metal ions, and the source of the plant-derived OC. Up to 63% of the signaling repression occurs between dissolved OC and flavonoids rather than through flavonoid sorption to particulate OC. In plant experiments, OC interrupts the signaling between a legume and a nitrogen-fixing microbial symbiont, resulting in a 75% decrease in nodule formation. Our results suggest that soil OC decreases the lifetime of flavonoids underlying plant-microbe interactions.
A yeast-expressed RBD-based SARS-CoV-2 vaccine formulated with 3M-052-alum adjuvant promotes protective efficacy in non-human primates
An adjuvanted monomeric RBD immunogen induces immunogenicity and protective immunity against SARS-CoV-2 in rhesus macaques.
A novel Shiga toxin 2a neutralizing antibody therapeutic with low immunogenicity and high efficacy
ABSTRACT Shiga toxin-producingEscherichia coliinfections are difficult to treat due to the risk of antibiotic-induced stress upregulating the production of toxins, medical treatment is consequently limited to supportive care to prevent the development of hemolytic uremic syndrome (HUS). Here, we introduce a potentially therapeutic humanized mouse monoclonal antibody (Hu-mAb 2-5) targeting Stx2a, the most common Shiga toxin subtype identified from outbreaks. We demonstrate that Hu-mAb 2-5 has low immunogenicity in healthy adultsex vivoand high neutralizing efficacyin vivo, protecting mice from mortality and HUS-related tissue damage.
Discovery of GuaB inhibitors with efficacy against Acinetobacter baumannii infection
ABSTRACT Guanine nucleotides are required for growth and viability of cells due to their structural role in DNA and RNA, and their regulatory roles in translation, signal transduction, and cell division. The natural antibiotic mycophenolic acid (MPA) targets the rate-limiting step inde novoguanine nucleotide biosynthesis executed by inosine-5´-monophosphate dehydrogenase (IMPDH). MPA is used clinically as an immunosuppressant, but whetherin vivoinhibition of bacterial IMPDH (GuaB) is a valid antibacterial strategy is controversial. Here, we describe the discovery of extremely potent small molecule GuaB inhibitors (GuaBi) specific to pathogenic bacteria with a low frequency of on-target spontaneous resistance and bactericidal efficacyin vivoagainstAcinetobacter baumanniimouse models of infection. The spectrum of GuaBi activity includes multidrug-resistant pathogens that are a critical priority of new antibiotic development. Co-crystal structures ofA. baumannii, Staphylococcus aureus, andEscherichia coliGuaB proteins bound to inhibitors show comparable binding modes of GuaBi across species and identifies key binding site residues that are predictive of whole-cell activity across both Gram-positive and Gram-negative clades of Bacteria. The clearin vivoefficacy of these small molecule GuaB inhibitors in a model ofA. baumanniiinfection validates GuaB as an essential antibiotic target. IMPORTANCE The emergence of multidrug-resistant bacteria worldwide has renewed interest in discovering antibiotics with novel mechanism of action. For the first time ever, we demonstrate that pharmacological inhibition ofde novoguanine biosynthesis is bactericidal in a mouse model ofAcinetobacter baumanniiinfection. Structural analyses of novel inhibitors explain differences in biochemical and whole-cell activity across bacterial clades and underscore why this discovery may have broad translational impact on treatment of the most recalcitrant bacterial infections.
Efficacy of using a dynamic length representation vs. a fixed-length for neuroarchitecture search
Deep learning neuroarchitecture and hyperparameter search are important in finding the best configuration that maximizes learned model accuracy. However, the number of types of layers, their associated hyperparameters, and the myriad of ways to connect layers poses a significant computational challenge in discovering ideal model configurations. Here, we assess two different approaches for neuroarchitecture search for a LeNet style neural network, one that uses a fixed-length approach where there is a preset number of possible layers that can be toggled on or off via mutation, and a variable-length approach where layers can be freely added or removed via special mutation operators. We found that the variable-length implementation trained better models while discovering unusual layer configurations worth further exploration.
Exploring the efficacy of ether-based ignition enhancers for implementation of (M) ethanol mixing-controlled compression ignition combustion
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Efficacy of epetraborole against Mycobacterium abscessus is increased with norvaline
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Efficacy of commercial recombinant HVT vaccines against a North American clade 2.3.4.4b H5N1 highly pathogenic avian influenza virus in chickens
The outbreak of clade 2.3.4.4b H5 highly pathogenic avian influenza (HPAI) in North America that started in 2021 has increased interest in applying vaccination as a strategy to help control and prevent the disease in poultry. Two commercially available vaccines based on the recombinant herpes virus of turkeys (rHVT) vector were tested against a recent North American clade 2.3.4.4b H5 HPAI virus isolate: A/turkey/Indiana/22-003707-003/2022 H5N1 in specific pathogen free white leghorn (WL) chickens and commercial broiler chickens. One rHVT-H5 vaccine encodes a hemagglutinin (HA) gene designed by the computationally optimized broadly reactive antigen method (COBRA-HVT vaccine). The other encodes an HA gene of a clade 2.2 virus (2.2-HVT vaccine). There was 100% survival of both chicken types COBRA-HVT vaccinated groups and in the 2.2-HVT vaccinated groups there was 94.8% and 90% survival of the WL and broilers respectively. Compared to the 2.2-HVT vaccinated groups, WL in the COBRA-HVT vaccinated group shed significantly lower mean viral titers by the cloacal route and broilers shed significantly lower titers by the oropharyngeal route than broilers. Virus titers detected in oral and cloacal swabs were otherwise similar among both vaccine groups and chicken types. To assess antibody-based tests to identify birds that have been infected after vaccination (DIVA-VI), sera collected after the challenge were tested with enzyme-linked lectin assay-neuraminidase inhibition (ELLA-NI) for N1 neuraminidase antibody detection and by commercial ELISA for detection of antibodies to the NP protein. As early as 7 days post challenge (DPC) 100% of the chickens were positive by ELLA-NI. ELISA was less sensitive with a maximum of 75% positive at 10DPC in broilers vaccinated with 2.2-HVT. Both vaccines provided protection from challenge to both types of chickens and ELLA-NI was sensitive at identifying antibodies to the challenge virus therefore should be evaluated further for DIVA-VI.