Engineering Papers⌕ Search

SEARCH · Engineering Papers

Results for “130 BASIC BIOLOGICAL SCIENCES”

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.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

23 records · Page 2
All sourcesNASA NTRSDOE OSTI
DOE OSTI2020

Hormonal contraception alters vaginal microbiota and cytokines in South African adolescents in a randomized trial

Young women in sub-Saharan Africa are disproportionally affected by HIV infection and unintended pregnancies. However, hormonal contraceptive (HC) use may influence HIV risk through changes in genital tract microbiota and inflammatory cytokines. To investigate this, 130 HIV negative adolescent females aged 15–19 years were enrolled into a substudy of UChoose, an open-label randomized crossover study (NCT02404038), comparing acceptability and contraceptive product preference as a proxy for HIV prevention delivery methods. Participants were randomized to injectable norethisterone enanthate (Net-En), combined oral contraceptives (COC) or etonorgesterol/ethinyl estradiol combined contraceptive vaginal ring (CCVR) for 16 weeks, then crossed over to another HC for 16 weeks. Cervicovaginal samples were collected at baseline, crossover and exit for characterization of the microbiota and measurement of cytokine levels; primary endpoints were cervical T cell activation, vaginal microbial diversity and cytokine concentrations. Adolescents randomized to COCs had lower vaginal microbial diversity and relative abundance of HIV risk-associated taxa compared to Net-En or CCVR. Cervicovaginal inflammatory cytokine concentrations were significantly higher in adolescents randomized to CCVR compared to COC and Net-En. This suggests that COC use may induce an optimal vaginal ecosystem by decreasing bacterial diversity and inflammatory taxa, while CCVR use is associated with genital inflammation.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2023

3-O-Methyltolcapone and Its Lipophilic Analogues Are Potent Inhibitors of Transthyretin Amyloidogenesis with High Permeability and Low Toxicity

Transthyretin (TTR) is an amyloidogenic homotetramer involved in the transport of thyroxine in blood and cerebrospinal fluid. To date, more than 130 TTR point mutations are known to destabilise the TTR tetramer, leading to its extracellular pathological aggregation accumulating in several organs, such as heart, peripheral and autonomic nerves, and leptomeninges. Tolcapone is an FDA-approved drug for Parkinson’s disease that has been repurposed as a TTR stabiliser. We characterised 3-O-methyltolcapone and two newly synthesized lipophilic analogues, which are expected to be protected from the metabolic glucuronidation that is responsible for the lability of tolcapone in the organism. Immunoblotting assays indicated the high degree of TTR stabilisation, coupled with binding selectivity towards TTR in diluted plasma of 3-O-methyltolcapone and its lipophilic analogues. Furthermore, in vitro toxicity data showed their several-fold improved neuronal and hepatic safety compared to tolcapone. Calorimetric and structural data showed that both T4 binding sites of TTR are occupied by 3-O-methyltolcapone and its lipophilic analogs, consistent with an effective TTR tetramer stabilisation. Moreover, in vitro permeability studies showed that the three compounds can effectively cross the blood-brain barrier, which is a prerequisite for the inhibition of TTR amyloidogenesis in the cerebrospinal fluid. Our data demonstrate the relevance of 3-O-methyltolcapone and its lipophilic analogs as potent inhibitors of TTR amyloidogenesis.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2022

Effect of vaccination on the case fatality rate for COVID-19 infections 2020–2021: multivariate modelling of data from the US Department of Veterans Affairs

Objectives: To evaluate the benefits of vaccination on the case fatality rate (CFR) for COVID-19 infections. Design, setting and participants: The US Department of Veterans Affairs has 130 medical centres. We created multivariate models from these data—339 772 patients with COVID-19—as of 30 September 2021. Outcome measures: The primary outcome for all models was death within 60 days of the diagnosis. Logistic regression was used to derive adjusted ORs for vaccination and infection with Delta versus earlier variants. Models were adjusted for confounding factors, including demographics, comorbidity indices and novel parameters representing prior diagnoses, vital signs/baseline laboratory tests and outpatient treatments. Patients with a Delta infection were divided into eight cohorts based on the time from vaccination to diagnosis. A common model was used to estimate the odds of death associated with vaccination for each cohort relative to that of unvaccinated patients. Results: 9.1% of subjects were vaccinated. 21.5% had the Delta variant. 18 120 patients (5.33%) died within 60 days of their diagnoses. The adjusted OR for a Delta infection was 1.87±0.05, which corresponds to a relative risk (RR) of 1.78. The overall adjusted OR for prior vaccination was 0.280±0.011 corresponding to an RR of 0.291. Raw CFR rose steadily after 10–14 weeks. The OR for vaccination remained stable for 10–34 weeks. Conclusions: Our CFR model controls for the severity of confounding factors and priority of vaccination, rather than solely using the presence of comorbidities. Our results confirm that Delta was more lethal than earlier variants and that vaccination is an effective means of preventing death. After adjusting for major selection biases, we found no evidence that the benefits of vaccination on CFR declined over 34 weeks. We suggest that this model can be used to evaluate vaccines designed for emerging variants.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2020

GapMind: Automated Annotation of Amino Acid Biosynthesis

ABSTRACT GapMind is a Web-based tool for annotating amino acid biosynthesis in bacteria and archaea ( http://papers.genomics.lbl.gov/gaps ). GapMind incorporates many variant pathways and 130 different reactions, and it analyzes a genome in just 15 s. To avoid error-prone transitive annotations, GapMind relies primarily on a database of experimentally characterized proteins. GapMind correctly handles fusion proteins and split proteins, which often cause errors for best-hit approaches. To improve GapMind’s coverage, we examined genetic data from 35 bacteria that grow in defined media without amino acids, and we filled many gaps in amino acid biosynthesis pathways. For example, we identified additional genes for arginine synthesis with succinylated intermediates in Bacteroides thetaiotaomicron , and we propose that Dyella japonica synthesizes tyrosine from phenylalanine. Nevertheless, for many bacteria and archaea that grow in minimal media, genes for some steps still cannot be identified. To help interpret potential gaps, GapMind checks if they match known gaps in related microbes that can grow in minimal media. GapMind should aid the identification of microbial growth requirements. IMPORTANCE Many microbes can make all of the amino acids (the building blocks of proteins). In principle, we should be able to predict which amino acids a microbe can make, and which it requires as nutrients, by checking its genome sequence for all of the necessary genes. However, in practice, it is difficult to check for all of the alternative pathways. Furthermore, new pathways and enzymes are still being discovered. We built an automated tool, GapMind, to annotate amino acid biosynthesis in bacterial and archaeal genomes. We used GapMind to list gaps: cases where a microbe makes an amino acid but a complete pathway cannot be identified in its genome. We used these gaps, together with data from mutants, to identify new pathways and enzymes. However, for most bacteria and archaea, we still do not know how they can make all of the amino acids.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2021

Design Study for Bio-Oil Production from Biomass Using a Dual Fluidized-Bed Reactor

To evaluate the re-design and reconfiguration of a dual-fluidized bed (DFB) gasification system into a recirculating pyrolysis reactor, Computation Fluid Dynamic (CFD) simulations of the system were conducted. The Barracuda Virtual Reactor® computational particle fluid dynamic code was used to perform simulations of the pyrolysis process. Modeling of the chemical reaction kinetics for both gas phase and solid particle phase were included. The recirculating pyrolysis reactor shown in Fig. 1a is based on a bubbling-bed biomass pyrolyzer and a riser combustor to convert the remaining char. The operational differences in the re-configuration of the DFB gasification system into a recirculating pyrolysis system for the production of bio-oil are (1) replacement of a low-surface area inert bed material with a high-surface-area bed material that has acidic properties to provide catalytic activity for the production of bio-oil with reduced oxygen content, (2) lower temperature and residence time for bio-oil production from pyrolysis, (3) replacement of the fluidization gas in the bubbling bed pyrolyzer from steam to nitrogen, and (4) the reduction of pyrolyzer freeboard volume. The bed material used for catalytic pyrolysis is Sasol 300 (300-micron dia., bulk density 0.94 kg/l, and surface area 130 m2/g) and is a theta-alumina with mild acidity. This is in comparison with previous standard bed material Carbo HSP (430-micron dia., bulk density 2.01 kg/l, and surface area 0.03 m2/g) used for gasification. For bio-oil production, pyrolysis in the bubbling bed requires temperatures in the range of 550 C in comparison with gasification temperatures near 850 C. To attain this lower temperature requires management of the energy mass balances, with control of the bed material recirculation rate between bubbling bed pyrolyzer and riser combustor, the introduction of a nitrogen purge in the pyrolyzer, and adjusting the pressure balance between the two vessels. To extract bio-oil from the pyrolysis reactor with a snorkel, two different freeboard configurations were evaluated. In Fig. 1 b the existing high freeboard configuration is shown and in Fig. 1 c the reduced freeboard design is presented. The introduction of a nitrogen purge for the high free board configuration provided the highest bio-oil production from the CFD simulations. To decrease the bed-material circulation rate, primary and secondary air on the combustor side were reduced, and the pressure on the combustor was slightly increased. A portion of the biomass and bio-oil was observed to be transported to the combustor, leading to a smaller pyrolysis yield. The control of the pyrolyzer temperature is performed by controlling the circulation rate. Good fluidization of the bubbling bed and cascade PID control are required to keep the temperature from oscillating due to large time delay experienced when changing primary and secondary air. (a) (b) (c) Figure 1. (a) Dual Fluidized Bed pyrolysis system configuration, (b) mole fraction of nonpolar biooil in high freeboard configuration, and (c) mole fraction of nonpolar bio-oil in low freeboard configuration with nitrogen purge introduced in both configurations.

BASIC BIOLOGICAL SCIENCES,BIOMASS FUELS↗