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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 109 records · Page 6
All sourcesNASA NTRSDOE OSTI
DOE OSTI2021

High-throughput screening of the ReFRAME, Pandemic Box, and COVID Box drug repurposing libraries against SARS-CoV-2 nsp15 endoribonuclease to identify small-molecule inhibitors of viral activity

SARS-CoV-2 has caused a global pandemic, and has taken over 1.7 million lives as of mid-December, 2020. Although great progress has been made in the development of effective countermeasures, with several pharmaceutical companies approved or poised to deliver vaccines to market, there is still an unmet need of essential antiviral drugs with therapeutic impact for the treatment of moderate-to-severe COVID-19. Towards this goal, a high-throughput assay was used to screen SARS-CoV-2 nsp15 uracil-dependent endonuclease (endoU) function against 13 thousand compounds from drug and lead repurposing compound libraries. While over 80% of initial hit compounds were pan-assay inhibitory compounds, three hits were confirmed as nsp15 endoU inhibitors in the 1–20 μM range in vitro. Furthermore, Exebryl-1, a ß-amyloid anti-aggregation molecule for Alzheimer’s therapy, was shown to have antiviral activity between 10 to 66 μM, in Vero 76, Caco-2, and Calu-3 cells. Although the inhibitory concentrations determined for Exebryl-1 exceed those recommended for therapeutic intervention, our findings show great promise for further optimization of Exebryl-1 as an nsp15 endoU inhibitor and as a SARS-CoV-2 antiviral.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2024

Correlating transcription and protein expression profiles of immune biomarkers following lipopolysaccharide exposure in lung epithelial cells

Universal and early recognition of pathogens occurs through recognition of evolutionarily conserved pathogen associated molecular patterns (PAMPs) by innate immune receptors and the consequent secretion of cytokines and chemokines. The intrinsic complexity of innate immune signaling and associated signal transduction challenges our ability to obtain physiologically relevant, reproducible and accurate data from experimental systems. One of the reasons for the discrepancy in observed data is the choice of measurement strategy. Immune signaling is regulated by the interplay between pathogen-derived molecules with host cells resulting in cellular expression changes. However, these cellular processes are often studied by the independent assessment of either the transcriptome or the proteome. Correlation between transcription and protein analysis is lacking in a variety of studies. In order to methodically evaluate the correlation between transcription and protein expression profiles associated with innate immune signaling, we measured cytokine and chemokine levels following exposure of human cells to the PAMP lipopolysaccharide (LPS) from the Gram-negative pathogen Pseudomonas aeruginosa . Expression of 84 messenger RNA (mRNA) transcripts and 69 proteins, including 35 overlapping targets, were measured in human lung epithelial cells. We evaluated 50 biological replicates to determine reproducibility of outcomes. Following pairwise normalization, 16 mRNA transcripts and 6 proteins were significantly upregulated following LPS exposure, while only five (CCL2, CSF3, CXCL5, CXCL8/IL8, and IL6) were upregulated in both transcriptomic and proteomic analysis. This lack of correlation between transcription and protein expression data may contribute to the discrepancy in the immune profiles reported in various studies. The use of multiomic assessments to achieve a systems-level understanding of immune signaling processes can result in the identification of host biomarker profiles for a variety of infectious diseases and facilitate countermeasure design and development.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2026

Directed evolution of a stem-helix–targeting antibody enables MERS-CoV cross-neutralization through enhanced binding affinity

Broadly neutralizing antibodies (bnAbs) targeting conserved regions of the betacoronavirus spike are important for pan-betacoronavirus protection and pandemic preparedness. Here, we report the isolation of a human monoclonal antibody, CC65.1, from a SARS-CoV-2 convalescent donor that targets the conserved S2 stem helix region. CC65.1 neutralizes various sarbecoviruses, including SARS-CoV-2, and binds to the MERS-CoV spike but lacks MERS-CoV-neutralizing activity due to insufficient binding affinity. We utilized directed evolution to enhance the binding affinity of CC65.1 for the MERS-CoV S2 stem helix, yielding engineered antibody variants with newly acquired MERS-CoV-neutralizing activity. High-resolution structural analysis reveals key paratope mutations that enhance binding and stabilize epitope engagement. Our findings demonstrate the potential of in vitro affinity maturation to expand the neutralization breadth of stem-helix-targeting antibodies across divergent betacoronaviruses. This work supports the development of engineered bnAbs for broadly protective betacoronavirus countermeasures and provides a strategy for achieving cross-lineage neutralization.

Zhou, Panpan↗
DOE OSTI2020

Simulation of emergent compaction banding fronts caused by frictional boundaries

This study examines the role of boundary friction in promoting heterogeneous compaction in soft rock specimens loaded at high confining pressure outside the domain of compaction localisation. An elastoplastic constitutive model characterised by tunable hardening/softening behaviour is used to conduct the analyses. Finite-element simulations suggest that material instability is a non-necessary condition for the emergence of compaction fronts. Such fronts propagated as a result of a severe deviation in the local responses induced by frictional constraints. Overall, these findings suggest that boundary effects can bias the assessment of the extent of the compaction localisation domain. Experimental countermeasures and informed model calibration procedures are therefore necessary to minimise such bias and enable more accurate predictions of soft rock compaction.

42 ENGINEERING↗
DOE OSTI2020

Protein Factory on a Chip for Rapid Therapeutics

The potential for new, re-emerging, or engineered pandemic threats could challenge our nation's biosecurity, requiring rapid and flexible countermeasure development platforms. In healthcare, one of the main hindrances to the timely development of protein-based therapeutics for cancer, infectious disease, and other diseases has been a slow and expensive quality-controlled production stage. We present a protein-based technology that has the potential to address these crucial problems in biosecurity and healthcare by maximizing protein production and system portability, while minimizing production latency and cost. Specifically, we have developed a reusable, portable first-generation platform that leverages the advantages of cell-free protein synthesis (CFPS) and flow cells to create practical amounts of clinically relevant therapeutics. We have demonstrated that this technology is reusable and programmable, enabling a single platform that can synthesize multiple dosages of various therapeutics and vaccine in the field. Implementing this technology could mitigate pandemic threats by providing a rapidly-deployable (just-in-time), versatile (precision medicine) production of biologic therapeutics to the infected patient’s locale (point-of-care). In drug development, once promising drug variations are identified, the platform can be scaled to quickly produce practical amounts of protein for patient testing in the matter of days (vs. months) at a fraction of the cost of existing technology.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2020

332TFAD04 Tank Closure Plan

Enclosed is the 332TFAD04 Aboveground Tank Closure/Removal Plan for a tank regulated under Spill Prevention, Controls, and Countermeasures (SPCC) and Aboveground Petroleum Storage Act (APSA) regulations. This tank held diesel fuel for an emergency generator at Building 332. The generator is being replaced with a new unit that contains a belly tank, therefore this aboveground tank will no longer be in use and is being removed. The tank will be SPCC permanently closed on June 2, 2020.

12 MANAGEMENT OF RADIOACTIVE AND NON-RADIOACTIVE W↗
DOE OSTI2020

Cyber Security Analysis for Nuclear Reactor Control Systems (Final Technical Report)

This project investigated the cyber-security impacts of moving from an all analog, point-to-point, instrumentation and control (I&C) system to a digital I&C system based on Modbus and a shared communication medium. A formalism called a hybrid attack graph was expanded to support the nuclear research reactor system. The hybrid attack graph allows one to check a system for vulnerabilities, in this case cyber-security vulnerabilities, and to document the attack vectors (scenarios) causing those vulnerabilities. In parallel, a simulation of the system was developed to model both the physical reactor parameters and operations, as well as the network interconnects and communications. This simulation platform was modeled on the nuclear research reactor located at Washington State University. The simulation platform provided a sandbox to evaluate and quantify the impact of identified and proposed vulnerabilities in the system and to determine the effectiveness of countermeasures at stopping these attacks. The simulation and hybrid attack graph tools were integrated to provide a streamlined process of generating attack scenarios, playing those scenarios out in the simulation, and then analyzing the results to correlate system state to states in the hybrid attack graph. This process was used to (1) quantify the impact of attack scenarios and (2) to determine if the system moved through the hybrid attack graph as anticipated. The hybrid attack graph tool was extended and customized to produce a tool to automatically identify critical assets (CAs) and critical digital assets (CDAs) as defined by NRC Regulatory Guide 5.71. This tool was verified using the nuclear research reactor at Washington State University. Finally, a series of educational modules covering the findings of the different aspects of this research have been created.

97 MATHEMATICS AND COMPUTING↗
DOE OSTI2020

Bioscience COVID Rapid Response Report

The COVID-19 disease outbreak and its impact on global health and economies have highlighted the national security threat posed by pathogens with pandemic potential and the need for rapid development of effective diagnostics and medical countermeasures. The Bioscience IA selected for funding rapid COVID LDRD project proposals that addressed critical R&D gaps in pandemic response that could be accomplished in 1-3 months with the requested funding. In total, the Bioscience IA funded nine rapid projects that addressed 1) rapid and accurate methods for SARS-CoV-2 RNA detection, 2) modeling tools to help prioritize populations for diagnostic testing, 3) bioinformatic tools to track SARS-CoV-2 genomic sequence changes over time, 4) molecular inhibitors of SARS-CoV-2 cellular infection, and 5) method for rapid staging of COVID19 disease to enable administration of more effective treatments. In addition, LDRD funded one larger project to be completed in FY21 that leverages Sandia capabilities to address the need for platform diagnostics and therapeutics that can be rapidly tailored against emerging pathogen targets.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2020

Securing Vehicle Charging Infrastructure

As the US electrifies the transportation sector, cyber attacks targeting vehicle charging could bring consequences to electrical system infrastructure. This is a growing area of concern as charging stations increase power delivery and must communicate to a range of entities to authorize charging, sequence the charging process, and manage load (grid operators, vehicles, OEM vendors, charging network operators, etc.). The research challenges are numerous and are complicated because there are many end users, stakeholders, and software and equipment vendors interests involved. Poorly implemented electric vehicle supply equipment (EVSE), electric vehicle (EV), or grid communication system cybersecurity could be a significant risk to EV adoption because the political, social, and financial impact of cyberattacks - or public perception of such - ripples across the industry and has lasting and devastating effects. Unfortunately, there is no comprehensive EVSE cybersecurity approach and limited best practices have been adopted by the EV/EVSE industry. There is an incomplete industry understanding of the attack surface, interconnected assets, and unsecured interfaces. Thus, comprehensive cybersecurity recommendations founded on sound research are necessary to secure EV charging infrastructure. This project is providing the power, security, and automotive industry with a strong technical basis for securing this infrastructure by developing threat models, determining technology gaps, and identifying or developing effective countermeasures. Specifically, the team is creating a cybersecurity threat model and performing a technical risk assessment of EVSE assets, so that automotive, charging, and utility stakeholders can better protect customers, vehicles, and power systems in the face of new cyber threats.

33 ADVANCED PROPULSION SYSTEMS↗
DOE OSTI2020

Fossil Power Plant Cyber Security Life-Cycle Risk Reduction, A Practical Framework for Implementation

Market conditions are forcing fossil electricity generation facility owners and operators to implement advanced digital technologies. These technologies enable efficiencies, operational flexibility, operations and maintenance efficiencies, and adapting to a transitioning workforce. These digital technologies, however, can increase the cybersecurity attack surface. The purpose of this research was to develop a holistic cybersecurity risk reduction framework for fossil generation facilities. The framework begins with assessing how cyber risk changes across facility life cycles, including plant, system, vendor, and business life cycles. The next phase performs consequence analysis to prioritize high consequence events. Focusing on high consequence events allows owners to use a graded, risk-informed approach to prioritize cybersecurity efforts. The final phase identifies the digital asset attack surface in sensors and instrumentation and control equipment. After the vulnerabilities are identified, the owner selects mitigating cybersecurity control measures (or countermeasures) based on the risk analysis from the previous phases. This report describes the current industry cybersecurity best practices in fossil generation that are based on the first principles for cybersecurity engineering. The report is divided into five sections that describe the implementation of the risk reduction framework and present identified research, methodological, and technology gaps that were identified through this course of research and development.

01 COAL, LIGNITE, AND PEAT↗
DOE OSTI2021

Critical steps in preventing future pandemics. Early lessons from the Covid-19 crisis for addressing natural and deliberate biological threats.

This report summarizes a virtual workshop on early lessons from the COVID-19 pandemic as they pertain to proactively addressing future biological threats. Co-hosted by Sandia National Laboratory (Sandia) and the Council on Strategic Risks (CSR) in August 2020, the discussion involved experts who at that time were leading innovative efforts in various U.S. government agencies, industry, and academia sharing observations from their ongoing pandemic response efforts. Based on the input by these expert participants, it is clear that even though the pandemic response is ongoing, the following recommendations will be important to consider for more successfully addressing biological threats in the future: Continue building on the cross-sector collaboration and agility shown in the COVID-19 response; Expand capabilities for detecting biological threats early; Prioritize ways to create and disseminate medical countermeasures even faster; Create the U.S. bio industrial base needed for rapid response to biological threats, and keep it healthy; and, Major government reorganization may not be needed if there is effective work to form coalitions, improve coordination, and expand steady-state and surge capacities.

29 ENERGY PLANNING, POLICY, AND ECONOMY↗
DOE OSTI2021

Science and Technology Review June 2021

When the COVID-19 pandemic hit, Lawrence Livermore National Laboratory scientists came together, leveraging many different disciplines and technologies to address this global challenge. Livermore focused on three areas of research: creating alternatives for medical equipment in short supply, such as ventilators and nasal swabs; developing methods to help detect the SARS-CoV-2 virus responsible for COVID-19; and designing medical countermeasures such as antibodies and antivirals to combat the disease.

36 MATERIALS SCIENCE↗
DOE OSTI2022

Protection and Restoration Solutions to Reliable and Resilient Integration of Grid-connected PV Installations and Distributed Energy Resources: Design, Testbed, Proof of Work and Impact Studies (Final Report)

To gain a better understanding of the complex transients in a utility grid with a large number of solar PV installations coupled by PWM inverters during the protection and restoration period of the power grid, in this project a kW-level experimental system with dominating inverter-based resources and a hardware-in-loop simulation system with transmission and distribution models, as well as several SEL protective relays have been built and used. The major research findings of the project are summarized below in two perspectives: Experimental research: A self-organized ultra-high frequency solitary waveform is discovered and demonstrated in the hardware experimental system. Despite the familiarities, such a solitary waveform is distinct from any harmonics, transient, or resonance waves in that, it is 1) non-dispersive over time and space, 2) not associated with any active source or the linear superposition of sources, 3) half-cycle asymmetric, 4) not responding to filters or change of system characteristic resonance frequency, 5) ubiquitous as it occurs simultaneously everywhere in the system from DC supply, power lines, and the utility grid, and 6) explosive through tripping the protection or damaging susceptible devices or circuits. Analytical study: The nature of such a new waveform and an analytical explanation of its formation are studied based on related physics and non-linear science principles, with the following highlights: 1) such a new waveform follows the solutions to the Non-linear Schrödinger equation, so the classic linear perturbation theory is unable to explain or predict such a unique waveform as confirmed with the research team of RTDS; 2) the critical condition of occurrence of such a waveform is derived, which indicates that the breakings of solitary wave is a system synchronous issue between the utility grid in the 60Hz phasor domain and duty-ratio modulation of DC sources in the inverter switching frequency domain; 3) such a waveform carries energy mass so it could be detrimental; 4) such a waveform is deceiving as it is not readily detectable in the energy propagation direction by the primary protection equipment, while it is detrimental in the perpendicular direction of energy propagation, i.e. voltage direction. Thus, it has more likely challenges to the second primary equipment and devices, particularly at the weakest link and point such as aging insulation and inappropriate setting of susceptible devices. Therefore, such a waveform can be easily ignored in the aftermath investigation. The intellectual merits: The experimental discovery reveals certain unfamiliar transient phenomena that could challenge the integration of large-scale grid-connected solar PV installation during the group ride-through period of solar PV installations, commissioning of large-solar farms, or dramatic change of solar radiation conditions. Particularly, the research findings suggest that the occurrence of the unfamiliar transient phenomena is uniquely associated with the inverter-based solar PV installation, which is less likely to happen for rotary energy systems. The physics and non-linear science-based research work laid down an analytical path to the challenging transient stability problems including those that have been observed currently and future calls. Both experimental and analytical research results explain the limitation of many current research effects including some DoE research undertakings as well as possible solutions. The broader impacts: The research outcome of the project advances the understanding of the possible transient problems for the integration of inverter-based solar PV installation. It also highlights the theoretical and technical barriers for applying the conventional theory and technology to design and implement countermeasures against their adverse impacts of the large-scale solar PV installation and operation on grid reliability and security. More broadly, the research outcomes have shed some light on the open, fundamental challenges in the integration of large-scale solar photovoltaic energy into current and next-generation power grids across the country, and worldwide. The advanced physics and non-linear science-based analysis open up a path to harmonization of the renewables for societal energy needs via building a resilient and sustainable electric power infrastructure.

14 SOLAR ENERGY↗
DOE OSTI2022

BayoTech Risk and Modeling Support of NM Gas Site

The BayoTech hydrogen generation system has been evaluated in terms of safety considerations at the NM Gas site. The consequence of a leak in different components in the system was evaluated in terms of plume dispersion and overpressure. Additionally, the likelihood of a leak scenario for different hydrogen components was identified. The worst-case plume dispersion cases, full-bore leaks, resulted in relatively large plumes. However, these cases were noted to be far less likely than the partial break cases that were evaluated. The partial break cases resulted in nearly negligible plume lengths. Similarly, the overpressure analysis of the full-bore break scenarios resulted in much larger overpressures than the partial break cases (which resulted in negligible overpressure at the lot line). There were several cases evaluated in the analysis that represented leak scenarios from both hydrogen and natural gas sources. Generally, the natural gas leak scenarios resulted in a smaller horizontal impact than that of hydrogen leaks. The worst-case consequence from a hydrogen leak resulted from the compressors, storage pods, or dispensing system. To consider the safety features that may isolate the leak, the consequence was evaluated at different times after the leak event to show the reduction of pressure. After 2 seconds, the plume dispersion from this event is contained within the perimeter of the site. The worst-case consequences show that the plume may disperse to adjacent facilities and to the street. When considering both likelihood and consequence, the risk may be considered low because the maximum frequency of a full-bore leak from any component within the hydrogen compound is 8.2 E-5/yr. This means that a full-bore leak is expected to occur less than once every 10,000 years. The risk can be further reduced by implementing mitigative countermeasures, such as CMU walls along the sides of the equipment compound. This would reduce the overall consequence of the worst-case dispersion scenarios (horizontal impact of plume). In terms of siting and safety analysis, the NFPA 2 code was used to provide a high-level evaluation of the current site plan. The most limiting equipment in terms of set-back distance are the compressors/storage units because of the high-pressure hydrogen. The site layout was evaluated for an acceptable location for the compression/storage unit based on NFPA 2 set-back distances. It is important to note that the NFPA 2 set-back distances consider both likelihood and consequence. This is important because the worst-case results evaluated herein also represent the least likely leak scenario. Other site-specific considerations were evaluated, including the parking shade structure with photovoltaic cells and refueling vehicles. These issues were dispositioned and determined to not present a safety risk.

08 HYDROGEN↗
DOE OSTI2022

Cybersecurity for Electric Vehicle Charging Infrastructure

As the U.S. electrifies the transportation sector, cyberattacks targeting vehicle charging could impact several critical infrastructure sectors including power systems, manufacturing, medical services, and agriculture. This is a growing area of concern as charging stations increase power delivery capabilities and must communicate to authorize charging, sequence the charging process, and manage load (grid operators, vehicles, OEM vendors, charging network operators, etc.). The research challenges are numerous and complicated because there are many end users, stakeholders, and software and equipment vendors interests involved. Poorly implemented electric vehicle supply equipment (EVSE), electric vehicle (EV), or grid operator communication systems could be a significant risk to EV adoption because the political, social, and financial impact of cyberattacks — or public perception of such — would ripple across the industry and produce lasting effects. Unfortunately, there is currently no comprehensive EVSE cybersecurity approach and limited best practices have been adopted by the EV/EVSE industry. There is an incomplete industry understanding of the attack surface, interconnected assets, and unsecured inter faces. Comprehensive cybersecurity recommendations founded on sound research are necessary to secure EV charging infrastructure. This project provided the power, security, and automotive industry with a strong technical basis for securing this infrastructure by developing threat models, determining technology gaps, and identifying or developing effective countermeasures. Specifically, the team created a cybersecurity threat model and performed a technical risk assessment of EVSE assets across multiple manufacturers and vendors, so that automotive, charging, and utility stakeholders could better protect customers, vehicles, and power systems in the face of new cyber threats.

24 POWER TRANSMISSION AND DISTRIBUTION↗
DOE OSTI2022

Combined Imaging and RNA-Seq on a Microfluidic Platform for Viral Infection Studies

The goal of this work was to pioneer a novel, low-overhead protocol for simultaneously assaying cell-surface markers and intracellular gene expression in a single mammalian cell. The purpose of developing such a method is to be able to understand the mechanisms by which pathogens engage with individual mammalian cells, depending on their cell surface proteins, and how both host and pathogen gene expression changes are reflective of these mechanisms. The knowledge gained from such analyses of single cells will ultimately lead to more robust pathogen detection and countermeasures. Our method was aimed at streamlining both the upstream cell sample preparation using microfluidic methods, as well as the actual library making protocol. Specifically, we wanted to implement a random hexamer-based reverse transcription of all RNA within a single cell (as opposed to oligo dT-based which would only capture polyadenylated transcripts), and then use a CRISPR-based method called scDash to deplete ribosomal DNAs (since ribosomal RNAs make up the majority of the RNA in a mammalian cell). After significant troubleshooting, we demonstrate that we are able to prepare cDNA from RNA using the random hexamer primer, and perform the rDNA depletion. We also show that we can visualize individually stained cells, setting up the pipeline for connecting surface markers to RNA-sequencing profiles. Finally, we test a number of devices for various parts of the pipeline, including bead generation, optical barcoding and cell dispensing, and demonstrate that while some of these have potential, more work is needed to optimize this part of the pipeline.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2021

Nanoparticle Mediated Delivery of Therapeutic mRNA for Protection Against Lung Damage

Medical countermeasures (MCMs) based on messenger ribonucleic acid (mRNA) are promising due to their programmability, targeting precision and specificity, predictable physicochemical properties, and amenability to scalable manufacture. However, safe and effective delivery vehicles are needed, especially for targeting the lung. We developed a generalized approach to nanoparticle-mediated mRNA delivery to lung, and used it to evaluate candidate therapies. In initial studies, reporter mRNA was delivered using lipid-coated mesoporous silica nanoparticles (LC-MSNs) and lipid nanoparticles (LNPs), the latter with greater consistency. Then, mRNA encoding known protein therapies were delivered using LNPs. These formulations showed some toxicity in mice with lung damage, but those with IL-1RA, sACE2-Ig, and ANGPT1 mRNA were modestly therapeutic on balance. Our work advances the state of the art for mRNA delivery to lung, and provides a foundation for evaluating and characterizing mRNA-based lung therapies, including three that appear to be exceptionally promising.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2022

Reconfiguration of the Respiratory Tract Microbiome to Prevent and Treat Burkholderia Infection

New approaches to preventing and treating infections, particularly of the respiratory tract, are needed. One promising strategy is to reconfigure microbial communities (microbiomes) within the host to improve defense against pathogens. Probiotics and prebiotics for gastrointestinal (GI) infections offer a template for success. We sought to develop comparable countermeasures for respiratory infections. First, we characterized interactions between the airway microbiome and a biodefense-related respiratory pathogen ( Burkholderia thailandensis ; Bt), using a mouse model of infection. Then, we recovered microbiome constituents from the airway and assessed their ability to re-colonize the airway and protect against respiratory Bt infection. We found that microbiome constituents belonging to Bacillus and related genuses frequently displayed colonization and anti-Bt activity. Comparative growth requirement profiling of these Bacillus strains vs Bt enabled identification of candidate prebiotics. This work serves as proof of concept for airway probiotics, as well as a strong foundation for development of airway prebiotics.

59 BASIC BIOLOGICAL SCIENCES↗