Engineering Papers⌕ Search

SEARCH · Engineering Papers

Results for “pharmaceuticals”

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.

At least 73 records · Page 4
All sourcesNASA NTRSDOE OSTI
DOE OSTI2026

Heterogeneous estimations of non-pharmaceutical mitigation behavior during the COVID-19 pandemic

The COVID-19 pandemic highlighted the importance of human behavior in mitigating the spread of disease. Nonetheless, human behavior is often overlooked in models of disease spread, particularly by underutilizing real-world data. We address this by estimating probabilities that individuals engage in behaviors that influence SARS-CoV-2 transmission risk during the COVID-19 pandemic, between September 2020 and June 2022. These behaviors include wearing a mask, using public transportation, spending time with others, avoiding contact with others, and going to work. Our estimates account for the age and sex of individuals and are generated for every county in the United States. We utilized multiple open-source datasets and United States Census data to produce these estimates. Multiple datasets were used for validation, showing our estimates demonstrated comparable accuracy and robustness. Our estimates aid in understanding human behavior dynamics during the COVID-19 pandemic and could be used to inform monthly or longer-term behavior in simulations of COVID-19. Moreover, the methods presented can be applied to other behaviors and features for future simulations of infectious disease.

97 MATHEMATICS AND COMPUTING↗
DOE OSTI2023

Controlling the toxicity of biomass-derived difunctional molecules as potential pharmaceutical ingredients for specific activity toward microorganisms and mammalian cells

A biomass-derived difuran compound, denoted as HAH (HMF–acetone–HMF), synthesized by aldol-condensation of 5-hydroxyfurfural (HMF) and acetone, can be partially hydrogenated to provide an electron-rich difuran compound (PHAH) for Diels–Alder reactions with maleimide derivatives. The nitrogen (N) site in the maleimide can be substituted by imidation with amine-containing compounds to control the hydrophobicity of the maleimide moiety in adducts of furans and maleimide by Diels–Alder reaction, denoted as norcantharimides (Diels–Alder adducts). The structural effects on the toxicity of various biomass-derived small molecules synthesized in this manner to regulate biological processes, defined as low molecular weight (≤1000 g mol -1 ) organic compounds, were investigated against diverse microbial and mammalian cell types. The biological toxicity increased when hydrophobic N-substitutions and C[double bond, length as m-dash]C bonds were introduced into the molecular structure. Among the synthesized norcantharamide derivatives, some compounds demonstrated pH-dependent toxicities against specific cell types. Reaction kinetics analyses of the norcantharimides in biological conditions suggest that this pH-dependent toxicity of norcantharimides could arise from retro Diels–Alder reactions in the presence of a Brønsted acid that catalyzes the release of an N-substituted maleimide, which has higher toxicity against fungal cells than the toxicity of the Diels–Alder adduct. These synthetic approaches can be used to design biologically-active small molecules that exhibit selective toxicity against various cell types (e.g., fungal, cancer cells) and provide a sustainable platform for production of prodrugs that could actively or passively affect the viability of infectious cells.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2024

Dinickel enzyme evolved to metabolize the pharmaceutical metformin and its implications for wastewater and human microbiomes

Metformin is the first-line treatment for type II diabetes patients and a pervasive pollutant with more than 180 million kg ingested globally and entering wastewater. The drug’s direct mode of action is currently unknown but is linked to effects on gut microbiomes and may involve specific gut microbial reactions to the drug. In wastewater treatment plants, metformin is known to be transformed by microbes to guanylurea, although genes encoding this metabolism had not been elucidated. In the present study, we revealed the function of two genes responsible for metformin decomposition (mfmA and mfmB) found in isolated bacteria from activated sludge. MfmA and MfmB form an active heterocomplex (MfmAB) and are members of the ureohydrolase protein superfamily with binuclear metal-dependent activity. MfmAB is nickel-dependent and catalyzes the hydrolysis of metformin to dimethylamine and guanylurea with a catalytic efficiency (k cat /K M ) of 9.6 × 10 3 M -1 s -1 and KM for metformin of 0.82 mM. MfmAB shows preferential activity for metformin, being able to discriminate other close substrates by several orders of magnitude. Crystal structures of MfmAB show coordination of binuclear nickel bound in the active site of the MfmA subunit but not MfmB subunits, indicating that MfmA is the active site for the MfmAB complex. Mutagenesis of residues conserved in the MfmA active site revealed those critical to metformin hydrolase activity and its small substrate binding pocket allowed for modeling of bound metformin. In conclusion, this study characterizes the products of the mfmAB genes identified in wastewater treatment plants on three continents, suggesting that metformin hydrolase is widespread globally in wastewater.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2022

High-Throughput Microbial Community Analyses to Establish a Natural Fungal and Bacterial Consortium from Sewage Sludge Enriched with Three Pharmaceutical Compounds

Emerging and unregulated contaminants end up in soils via stabilized/composted sewage sludges, paired with possible risks associated with the development of microbial resistance to antimicrobial agents or an imbalance in the microbial communities. An enrichment experiment was performed, fortifying the sewage sludge with carbamazepine, ketoprofen and diclofenac as model compounds, with the aim to obtain strains with the capability to transform these pollutants. Culturable microorganisms were obtained at the end of the experiment. Among fungi, Cladosporium cladosporioides, Alternaria alternata and Penicillium raistrickii showed remarkable degradation rates. Population shifts in bacterial and fungal communities were also studied during the selective pressure using Illumina MiSeq. These analyses showed a predominance of Ascomycota (Dothideomycetes and Aspergillaceae) and Actinobacteria and Proteobacteria, suggesting the possibility of selecting native microorganisms to carry out bioremediation processes using tailored techniques.

59 BASIC BIOLOGICAL SCIENCES↗
NASA NTRS1979

Study of pharmaceutical industrial problems

The growth of a human colon carcinoma cell line (SK-CO-1) and its production of carcinoembryonic antigen (CEA) in monolayer culture and on single layers of glass beads in unit gravity were evaluated. The limitations of using a microsphere-cell growth system in unit gravity were identified and how these may be overcome in space was considered. The project had the following tasks: (1) growth of cultured human colon carcinoma cells on a monolayer and CEA production; (2) evaluation of CEA production and release by SK-CO-1 cells grown on glass beads; (3) evaluation of other microcarriers for growing SK-CO-1 cells and determination of the minimum amount of culture medium needed for cell growth; and (4) growth of SK-CO-1 cells on collagen monolayers and CEA production.

Pincus, J. H.↗
NASA NTRS2012

Pharmaceutical Product Development: Intranasal Scopolamine (INSCOP) Metered Dose Spray

Motion sickness (MS) has been a problem associated with space flight, the modern military and commercial air and water transportation for many years. Clinical studies have shown that scopolamine is the most effective medication for the prevention of motion sickness (Dornhoffer et al, 2004); however, the two most common methods of administration (transdermal and oral) have performance limitations that compromise its utility. Intranasal administration offers a noninvasive treatment modality, and has been shown to counter many of the problems associated with oral and transdermal administration. With the elimination of the first pass effect by the liver, intranasal delivery achieves higher and more reliable bioavailability than an equivalent oral dose. This allows for the potential of enhanced efficacy at a reduced dose, thus minimizing the occurrence of untoward side effects. An Intranasal scopolamine (INSCOP) gel formulation was prepared and tested in four ground-based clinical trials under an active Investigational New Drug (IND) application with the Food and Drug Administration (FDA). Although there were early indicators that the intranasal gel formulation was effective, there were aspects of formulation viscosity and the delivery system that were less desirable. The INSCOP gel formulation has since been reformulated into an aqueous spray dosage form packaged in a precise, metered dose delivery system; thereby enhancing dose uniformity, increased user satisfaction and palatability, and a potentially more rapid onset of action. Recent reports of new therapeutic indications for scopolamine has prompted a wide spread interest in new scopolamine dosage forms. The novel dosage form and delivery system of INSCOP spray shows promise as an effective treatment for motion sickness targeted at the armed forces, spaceflight, and commercial sea, air, and space travel markets, as well as prospective psychotherapy for mental and emotional disorders.

Putcha, Lakshmi↗
NASA NTRS2019

ExMC Approach to Pharmaceutical Stability Research: An Overview

Goals of Stability Studies: Identify medications that are stable under real and simulated space conditions, especially deep space radiation; Identify medications that are potent and safe after their expiration dates; Ultimately provide a safe and effective formulary for exploratory spaceflight missions. ExMC: Exploration Medical Capabilities.

Cory, Wendy↗
NASA NTRSDate not supplied

Evaluating Sensory Augmentation as A Non-Pharmaceutical Tool to Mitigate Motion Sickness and Enhance Sensorimotor Task Performance: A Pilot Study Using Simulated Capsule Wave Motion

Wave motion during capsule recovery operations can result in motion sickness and performance decrements exacerbating reentry sickness following long duration spaceflight. The purpose of this pilot study was (1) to validate a capsule wave motion simulation as a platform to evaluate motion sickness countermeasures and (2) to evaluate a sensory augmentation belt providing vibrotactile feedback of gravitational upright. Ten healthy subjects ages 38.0 ± 10.1 (6M|4F) were exposed to complex wave motions on a six degree-of-freedom platform that included pitch, roll, and heave at provocative stimulus frequencies (0.1-0.25 Hz) while seated in an illuminated cabin deprived of external visual cues. Subjects reported acute symptoms for up to three consecutive 15 min trials or until they reached a motion sickness endpoint of 8 pts on the Pensacola Diagnostic Index (PDI). Five subjects were randomly assigned to the Sensory Augmentation (SA) group while the other five served as controls (CN group). Based on a Motion Sickness Susceptibility Questionnaire, the two groups had similar motion sickness histories (susceptibility percentile ranking of CN group = 27.5 ± 63.6 in the CN group versus 27.5 ± 37.0 in the SA group, median ± IQR). The vibrotactile feedback consisted of a single array of 8 electromechanical tactors positioned around the torso on an adjustable belt (Engineering Acoustics, Inc) that utilized an integrated inertial measurement unit (IMU) to indicate the direction of upright (e.g., subject’s back tactor on during forward tilt). During each wave motion trial subjects performed a battery of four different tasks: tracking Earth vertical using a joystick with and without a secondary task (Paced Auditory Serial Addition Test), an eye-hand target acquisition task on a cabin-fixed tablet, and the psychomotor vigilance test (PVT). All ten subjects reported varying levels of motion sickness with 6 of 10 reaching a symptom endpoint. Interestingly, subjects anecdotally reported that engagement in the joystick tracking task was less provocative than tasks involving the cabin-fixed tablet or periods of no activity. Sensory augmentation appeared to delay symptom onset, with 2 of 5 subjects reaching an endpoint within the first 15 min trial in the CN group versus none in the SA group (PDI after 15 min = 6.0 ± 2.5 in the CN group versus 3.4 ± 2.5 in the SA group, mean ±std). Sensory augmentation also improved performance on the joystick tracking task at lower stimulus frequencies (0.1 Hz in roll and 0.2 Hz in pitch). Both CN and SA groups maintained a consistent level of performance on the eye-hand target acquisition and PVT throughout the baseline (no motion) and wave motion periods. Our results validated that the simulated capsule wave motion paradigm provides an effective motion sickness stressor. This paradigm is currently being used to investigate the efficacy of intranasal scopolamine to mitigate motion sickness. Sensory augmentation using vibrotactile feedback appears to improve spatial awareness and delay symptom onset during complex passive motion. One advantage of this portable belt design is that it incorporates all tactor drive and IMU circuitry and therefore could continue to be worn by crewmembers and serve as a balance aid during egress and ambulation with recovery operations.

A M Bollinger↗