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At least 1,765 records · Page 98
All sourcesNASA NTRSDOE OSTI
DOE OSTI2016

SU-G-201-13: Investigation of Dose Variation Induced by HDR Ir-192 Source Global Shift Within the Varian Ring Applicator Using Monte Carlo Methods

Purpose: The Varian tandem and ring applicators are used to deliver HDR Ir-192 brachytherapy for cervical cancer. The source path within the ring is hard to predict due to the larger interior ring lumen. Some studies showed the source could be several millimeters different from planned positions, while other studies demonstrated minimal dosimetric impact. A global shift can be applied to limit the effect of positioning offsets. The purpose of this study was to assess the necessities of implementing a global source shift using Monte Carlo (MC) simulations. Methods: The MCNP5 radiation transport code was used for all MC simulations. To accommodate TG-186 guidelines and eliminate inter-source attenuation, a BrachyVision plan with 10 dwell positions (0.5cm step sizes) was simulated as the summation of 10 individual sources with equal dwell times for simplification. To simplify the study, the tandem was also excluded from the MC model. Global shifts of ±0.1, ±0.3, ±0.5 cm were then simulated as distal and proximal from the reference positions. Dose was scored in water for all MC simulations and was normalized to 100% at the normalization point 0.5 cm from the cap in the ring plane. For dose comparison, Point A was 2 cm caudal from the buildup cap and 2 cm lateral on either side of the ring axis. With seventy simulations, 108 photon histories gave a statistical uncertainties (k=1) <2% for (0.1 cm)3 voxels. Results: Compared to no global shift, average Point A doses were 0.0%, 0.4%, and 2.2% higher for distal global shifts, and 0.4%, 2.8%, and 5.1% higher for proximal global shifts, respectively. The MC Point A doses differed by < 1% when compared to BrachyVision. Conclusion: Dose variations were not substantial for ±0.3 cm global shifts, which is common in clinical practice.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2014

A Viral RNA Structural Element Alters Host Recognition of Nonself RNA

Although interferon (IFN) signaling induces genes that limit viral infection, many pathogenic viruses overcome this host response. As an example, 2'-O methylation of the 5' cap of viral RNA subverts mammalian antiviral responses by evading restriction of Ifit1, an IFN-stimulated gene that regulates protein synthesis. However, alphaviruses replicate efficiently in cells expressing Ifit1 even though their genomic RNA has a 5' cap lacking 2'-O methylation. We show that pathogenic alphaviruses use secondary structural motifs within the 5' untranslated region (UTR) of their RNA to alter Ifit1 binding and function. Mutations within the 5'-UTR affecting RNA structural elements enabled restriction by or antagonism of Ifit1 in vitro and in vivo. These results identify an evasion mechanism by which viruses use RNA structural motifs to avoid immune restriction.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2016

Structural and molecular basis for Ebola virus neutralization by protective human antibodies

Ebola virus causes hemorrhagic fever with a high case fatality rate for which there is no approved therapy. Two human monoclonal antibodies, mAb100 and mAb114, in combination, protect nonhuman primates against all signs of Ebola virus disease, including viremia. Here, we demonstrate that mAb100 recognizes the base of the Ebola virus glycoprotein (GP) trimer, occludes access to the cathepsin-cleavage loop, and prevents the proteolytic cleavage of GP that is required for virus entry. We show that mAb114 interacts with the glycan cap and inner chalice of GP, remains associated after proteolytic removal of the glycan cap, and inhibits binding of cleaved GP to its receptor. These results define the basis of neutralization for two protective antibodies and may facilitate development of therapies and vaccines.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2022

Accelerated aging of all-inorganic, interface-stabilized perovskite solar cells

To understand degradation routes and improve the stability of perovskite solar cells (PSCs), accelerated aging tests are needed. Here, we use elevated temperatures (up to 110°C) to quantify the accelerated degradation of encapsulated CsPbI 3 PSCs under constant illumination. Incorporating a two-dimensional (2D) Cs 2 PbI 2 Cl 2 capping layer between the perovskite active layer and hole-transport layer stabilizes the interface while increasing power conversion efficiency of the all-inorganic PSCs from 14.9 to 17.4%. Devices with this 2D capping layer did not degrade at 35°C and required >2100 hours at 110°C under constant illumination to degrade by 20% of their initial efficiency. Degradation acceleration factors based on the observed Arrhenius temperature dependence predict intrinsic lifetimes of 51,000 ± 7000 hours (>5 years) operating continuously at 35°C.

Science & Technology - Other Topics↗
DOE OSTI2017

Glutathionylation of Yersinia pestis LcrV and Its Effects on Plague Pathogenesis

Glutathionylation, the formation of reversible mixed disulfides between glutathione and protein cysteine residues, is a posttranslational modification previously observed for intracellular proteins of bacteria. Here we show that Yersinia pestis LcrV, a secreted protein capping the type III secretion machine, is glutathionylated at Cys 273 and that this modification promotes association with host ribosomal protein S3 (RPS3), moderates Y. pestis type III effector transport and killing of macrophages, and enhances bubonic plague pathogenesis in mice and rats. Secreted LcrV was purified and analyzed by mass spectrometry to reveal glutathionylation, a modification that is abolished by the codon substitution Cys 273 Ala in lcrV . Moreover, the lcrV C273A mutation enhanced the survival of animals in models of bubonic plague. Investigating the molecular mechanism responsible for these virulence attributes, we identified macrophage RPS3 as a ligand of LcrV, an association that is perturbed by the Cys 273 Ala substitution. Furthermore, macrophages infected by the lcrV C273A variant displayed accelerated apoptotic death and diminished proinflammatory cytokine release. Deletion of gshB , which encodes glutathione synthetase of Y. pestis , resulted in undetectable levels of intracellular glutathione, and we used a Y. pestis Δ gshB mutant to characterize the biochemical pathway of LcrV glutathionylation, establishing that LcrV is modified after its transport to the type III needle via disulfide bond formation with extracellular oxidized glutathione. IMPORTANCE Yersinia pestis , the causative agent of plague, has killed large segments of the human population; however, the molecular bases for the extraordinary virulence attributes of this pathogen are not well understood. We show here that LcrV, the cap protein of bacterial type III secretion needles, is modified by host glutathione and that this modification contributes to the high virulence of Y. pestis in mouse and rat models for bubonic plague. These data suggest that Y. pestis exploits glutathione in host tissues to activate a virulence strategy, thereby accelerating plague pathogenesis.

Microbiology↗
DOE OSTI2025

Microbial vitamin biosynthesis links gut microbiota dynamics to chemotherapy toxicity

ABSTRACT Dose-limiting toxicities pose a major barrier to cancer treatment. While preclinical studies show that the gut microbiota influences and is influenced by anticancer drugs, data from patients paired with careful side effect monitoring remains limited. Here, we investigate capecitabine (CAP)-microbiome interactions through longitudinal metagenomic sequencing of stool from 56 advanced colorectal cancer patients. CAP significantly altered the gut microbiome, enriching for menaquinol (vitamin K2) biosynthesis genes. Transposon library screens, targeted gene deletions, and media supplementation revealed that menaquinol biosynthesis protectsEscherichia colifrom drug toxicity. Stool menaquinol gene and metabolite levels were associated with decreased peripheral sensory neuropathy. Machine learning models trained in this cohort predicted toxicities in an independent cohort. Taken together, these results suggest treatment-associated increases in microbial vitamin biosynthesis serve a chemoprotective role for bacterial and host cells. Further, our findings provide a foundation for in-depth mechanistic dissection, human intervention studies, and extension to other cancer treatments. IMPORTANCE Side effects are common during the treatment of cancer. The trillions of microbes found within the human gut are sensitive to anticancer drugs, but the effects of treatment-induced shifts in gut microbes for side effects remain poorly understood. We profiled gut microbes in colorectal cancer patients treated with capecitabine and carefully monitored side effects. We observed a marked expansion in genes for producing vitamin K2 (menaquinone). Vitamin K2 rescued gut bacterial growth and was associated with decreased side effects in patients. We then used information about gut microbes to develop a predictive model of drug toxicity that was validated in an independent cohort. These results suggest that treatment-associated increases in bacterial vitamin production protect both bacteria and host cells from drug toxicity, providing new opportunities for intervention and motivating the need to better understand how dietary intake and bacterial production of micronutrients like vitamin K2 influence cancer treatment outcomes.

Microbiology↗
DOE OSTI2016

Improved Bacterial 16S rRNA Gene (V4 and V4-5) and Fungal Internal Transcribed Spacer Marker Gene Primers for Microbial Community Surveys

We continue to uncover a wealth of information connecting microbes in important ways to human and environmental ecology. As our scientific knowledge and technical abilities improve, the tools used for microbiome surveys can be modified to improve the accuracy of our techniques, ensuring that we can continue to identify groundbreaking connections between microbes and the ecosystems they populate, from ice caps to the human body. It is important to confirm that modifications to these tools do not cause new, detrimental biases that would inhibit the field rather than continue to move it forward. We therefore demonstrated that two recently modified primer pairs that target taxonomically discriminatory regions of bacterial and fungal genomic DNA do not introduce new biases when used on a variety of sample types, from soil to human skin. This confirms the utility of these primers for maintaining currently recommended microbiome research techniques as the state of the art.

Walters, William↗
DOE OSTI2015

Raman spectroscopy of InGaAs/GaAs nanoheterostructures δ-doped with Mn

The results of complex studies of InGaAs/GaAs nanoheterostructures δ-doped with Mn are reported. The structures are grown by metal-organic vapor-phase epitaxy in combination with laser deposition. By confocal Raman spectroscopy, it is shown that the low-temperature δ-doped GaAs cap layers are of higher crystal quality compared to uniformly doped layers. Scattering of light in the coupled phonon-plasmon mode is observed. The appearance of this mode is conditioned by the diffusion of manganese from the δ-layer. The thickness of the cap layer is found to be d{sub c} ≈ 9–20 nm, optimal for attainment of the highest photoluminescence intensity of the quantum well and the highest layer concentration of holes by doping with manganese.

36 MATERIALS SCIENCE↗
DOE OSTI2017

InAs QDs in a metamorphic In{sub 0.25}Ga{sub 0.75}As matrix, grown by MOCVD

InAs quantum dots (QDs) in a metamorphic InGaAs matrix are grown by MOVPE (metal-organic vapor-phase epitaxy) on GaAs substrates. The QDs emit light in the range 1380–1400 nm at room temperature. A multilayer metamorphic buffer (MB) consisting of nine sublayers, each having a thickness of ~200 nm, is used to grow the structures. In each of the first seven sublayers, the indium content x successively increases by ~3.5% to reach a final value of 24.5%. Then a compensating sublayer with x = 28% and a final dislocation-free sublayer with x = 24.5% are grown. It is shown that the elastic strain relaxes with dislocation bending at both interfaces in the third, from the surface, sublayer, with the top layer being free of dislocations at both interfaces. The QDs are formed in the metamorphic matrix by the deposition of 2–2.5 InAs single layers at 520°C, with the subsequent overgrowth of a thin InGaAs layer (cap layer) at the same temperature. It is found that, to improve the optical and structural quality of the samples, it is necessary to raise the growth rate and reduce the concentration of indium in the cap layer with respect to the corresponding growth parameters of the last layer of the metamorphic buffer.

36 MATERIALS SCIENCE↗
DOE OSTI2017

Luminescence of a near-surface GaAs/AlAs heterojunction in AlAs-based heterostructures

It is necessary to protect the surface of AlAs-based heterostructures from oxidation using a GaAs cap layer because of the high reactivity of aluminum. Thus, the surface region of these heterostructures always contains a GaAs/AlAs heterojunction. Here, it is demonstrated that, under nonresonant photoexcitation, the photoluminescence spectrum of AlAs-based heterostructures features a band associated with this heterojunction. The intensity of this band is determined by the thickness and doping type of the GaAs cap layer.

36 MATERIALS SCIENCE↗
DOE OSTI2020

Models For Automated Screening Of Condition Report

As part of the corrective action program (CAP) at nuclear power plants, employees are given the opportunity and responsibility to identify issues and conditions present at the plant that may have an effect on the function of plant systems. When an employee identifies a potential issue, they create a condition report which is submitted to the CAP system. This condition report then goes through a screening process to determine the importance of the condition and thus the priority that must be placed on correcting it and/or preventing future issues. The purpose of this software is to assist with the screening process in an automated way using machine learning models. This software covers both the training of a machine learning model as well as applying the model to records.

Krome, Cameron↗
DOE OSTI2019

Cloud, Aerosol and Boundary Layer Structure across the Northeast Pacific Stratocumulus-Cumulus Transition as observed during CSET

During the Cloud System Evolution in the Trades (CSET) field study, 14 research flights of the National Science Foundation G-V sampled the stratocumulus-cumulus transition between Northern California and Hawaii and its synoptic variability. The G-V made vertically resolved measurements of turbulence, cloud microphysics, aerosol characteristics, and trace gases. It also carried dropsondes and a vertically pointing W-band radar and lidar. This paper summarizes these observations with the goals of fostering novel comparisons with theory, models and reanalyses, and satellite-derived products. A longitude-height binning and compositing strategy mitigates limitations of sparse sampling and spatiotemporal variability. Typically, a 1-km-deep decoupled stratocumulus-capped boundary layer near California evolved into 2-km-deep precipitating cumulus clusters surrounded by patches of thin stratus that dissipated toward Hawaii. Low cloud cover was correlated with estimated inversion strength more than with cloud droplet number, even though the thickest clouds were generally precipitating and ultraclean layers indicative of aerosol-cloud-precipitation interaction were common west of 140 degrees W. Accumulation-mode aerosol concentration correlated well with collocated cloud droplet number concentration and was typically largest near the surface. Aitken mode aerosol concentration was typically larger in the free troposphere. Wildfire smoke produced spikes of aerosol and trace gases on some flights. CSET data are compared with space-time collocated output from MERRA-2 reanalysis and from the CAM6 climate model run with winds and temperature nudged toward this reanalysis. The reanalysis compares better with the observed relative humidity than does nudged CAM6. Both vertically diffuse the stratocumulus cloud layer versus observations. MERRA-2 slightly underestimates in situ carbon monoxide measurements and underestimates ozone depletion within the boundary layer.

Bretherton, Christopher S.↗
DOE OSTI2021

Improved Prediction of Cold-Air Pools in the Weather Research and Forecasting Model Using a Truly Horizontal Diffusion Scheme for Potential Temperature

The terrain-following vertical coordinate system used by many atmospheric models, including the Weather Research and Forecasting (WRF) Model, is prone to errors in regions of complex terrain. These errors stem, in part, from the calculation of horizontal gradients within the diffusion term of the momentum or scalar evolution equations. In WRF, such gradients can be calculated along coordinate surfaces, or using metric terms that help account for grid skewness. However, neither of these options ensures a truly horizontal gradient calculation, especially if a grid cell is skewed enough that the heights of the neighboring grid points used in the calculation fall outside the vertical range of the cell. In this work, an improved scheme that uses Taylor series approximations to vertically interpolate variables to the level necessary for a truly horizontal gradient calculation is implemented in WRF for the diffusion of potential temperature. The scheme is validated using an atmosphere-at-rest configuration, in which spurious flows develop only as a result of numerical errors and can thus be used as a proxy for model performance. Following validation, the method is applied to the simulation of cold-air pools (CAPs), which occur in regions of complex terrain and are characterized by strong near-surface temperature gradients. Using the truly horizontal scheme, idealized simulations demonstrate reduced numerical mixing in a quiescent CAP, and a realistic case study in the Columbia River basin shows a reduction in positive wind speed bias by up to roughly 20% compared to observations from the Second Wind Forecast Improvement Project.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2015

Analytical platform evaluation for quantification of ERG in prostate cancer using protein and mRNA detection methods

Background: The established methods for detecting prostate cancer (CaP) are based on tests using PSA (blood), PCA3 (urine), and AMACR (tissue) as biomarkers in patient samples. The demonstration of ERG oncoprotein overexpression due to gene fusion in CaP has thus provided ERG as an additional biomarker. Based on this, we hypothesized that ERG protein quantification methods can be of use in the diagnosis of prostate cancer. Methods: Therefore, an antibody-free assay for ERG3 protein detection was developed based on PRISM (high-pressure high-resolution separations with intelligent selection and multiplexing)-SRM (selected reaction monitoring) mass spectrometry. We utilized TMPRSS2-ERG positive VCaP and TMPRSS2-ERG negative LNCaP cells to simulate three different sample types (cells, tissue, and post-DRE urine sediment). Results: Recombinant ERG3 protein spiked into LNCaP cell lysates could be detected at levels as low as 20 pg by PRISM-SRM analysis. The sensitivity of the PRISM-SRM assay was around approximately 10,000 VCaP cells in a mixed cell population model of VCaP and LNCaP cells. Interestingly, ERG protein could be detected in as few as 600 VCaP cells spiked into female urine. The sensitivity of the in-house enzyme-linked immunosorbent assay (ELISA) was similar to the PRISM-SRM assay, with detection of 30 pg of purified recombinant ERG3 protein and 10,000 VCaP cells. On the other hand, qRT-PCR exhibited a higher sensitivity, as TMPRSS2-ERG transcripts were detected in as few as 100 VCaP cells, in comparison to NanoString methodologies which detected ERG from 10,000 cells. Conclusions: Based on this data, we propose that the detection of both ERG transcriptional products with RNA-based assays, as well as protein products of ERG using PRISM-SRM assays, may be of clinical value in developing diagnostics and prognostics assays for prostate cancer given their sensitivity, specificity, and reproducibility.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2024

In-vivo Raman microspectroscopy reveals differential nitrate concentration in different developmental zones in Arabidopsis roots

Abstract Background Nitrate (NO 3 − ) is one of the two major forms of inorganic nitrogen absorbed by plant roots, and the tissue nitrate concentration in roots is considered important for optimizing developmental programs. Technologies to quantify the expression levels of nitrate transporters and assimilating enzymes at the cellular level have improved drastically in the past decade. However, a technological gap remains for detecting nitrate at a high spatial resolution. Using extraction-based methods, it is challenging to reliably estimate nitrate concentration from a small volume of cells (i.e., with high spatial resolution), since targeting a small or specific group of cells is physically difficult. Alternatively, nitrate detection with microelectrodes offers subcellular resolution with high cell specificity, but this method has some limitations on cell accessibility and detection speed. Finally, optical nitrate biosensors have very good ( in-vivo ) sensitivity (below 1 mM) and cellular-level spatial resolution, but require plant transformation, limiting their applicability. In this work, we apply Raman microspectroscopy for high-dynamic range in-vivo mapping of nitrate in different developmental zones of Arabidopsis thaliana roots in-situ . Results As a proof of concept, we have used Raman microspectroscopy for in-vivo mapping of nitrate content in roots of Arabidopsis seedlings grown on agar media with different nitrate concentrations. Our results revealed that the root nitrate concentration increases gradually from the meristematic zone (~ 250 µm from the root cap) to the maturation zone (~ 3 mm from the root cap) in roots grown under typical growth conditions used for Arabidopsis, a trend that has not been previously reported. This trend was observed for plants grown in agar media with different nitrate concentrations (0.5–10 mM). These results were validated through destructive measurement of nitrate concentration. Conclusions We present a methodology based on Raman microspectroscopy for in-vivo label-free mapping of nitrate within small root tissue volumes in Arabidopsis. Measurements are done in-situ without additional sample preparation. Our measurements revealed nitrate concentration changes from lower to higher concentration from tip to mature root tissue. Accumulation of nitrate in the maturation zone tissue shows a saturation behavior. The presented Raman-based approach allows for in-situ non-destructive measurements of Raman-active compounds.

Fernández González, Alma↗
DOE OSTI2015

Cellobionic acid utilization: from Neurospora crassa to Saccharomyces cerevisiae

Background: Economical production of fuels and chemicals from plant biomass requires the efficient use of sugars derived from the plant cell wall. Neurospora crassa, a model lignocellulosic degrading fungus, is capable of breaking down the complex structure of the plant cell wall. In addition to cellulases and hemicellulases, N. crassa secretes lytic polysaccharide monooxygenases (LPMOs), which cleave cellulose by generating oxidized sugars—particularly aldonic acids. However, the strategies N. crassa employs to utilize these sugars are unknown. Results: We identified an aldonic acid utilization pathway in N. crassa, comprised of an extracellular hydrolase (NCU08755), cellobionic acid transporter (CBT-1, NCU05853) and cellobionic acid phosphorylase (CAP, NCU09425). Extracellular cellobionic acid could be imported directly by CBT-1 or cleaved to gluconic acid and glucose by a β-glucosidase (NCU08755) outside the cells. Intracellular cellobionic acid was further cleaved to glucose 1-phosphate and gluconic acid by CAP. However, it remains unclear how N. crassa utilizes extracellular gluconic acid. The aldonic acid pathway was successfully implemented in Saccharomyces cerevisiae when N. crassa gluconokinase was coexpressed, resulting in cellobionic acid consumption in both aerobic and anaerobic conditions. Conclusions: We successfully identified a branched aldonic acid utilization pathway in N. crassa and transferred its essential components into S. cerevisiae, a robust industrial microorganism.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2016

CisSERS: Customizable In Silico Sequence Evaluation for Restriction Sites

High-throughput sequencing continues to produce an immense volume of information that is processed and assembled into mature sequence data. Here, data analysis tools are urgently needed that leverage the embedded DNA sequence polymorphisms and consequent changes to restriction sites or sequence motifs in a high-throughput manner to enable biological experimentation. Cis SERS was developed as a standalone open source tool to analyze sequence datasets and provide biologists with individual or comparative genome organization information in terms of presence and frequency of patterns or motifs such as restriction enzymes. Predicted agarose gel visualization of the custom analyses results was also integrated to enhance the usefulness of the software. Cis SERS offers several novel functionalities, such as handling of large and multiple datasets in parallel, multiple restriction enzyme site detection and custom motif detection features, which are seamlessly integrated with real time agarose gel visualization. Using a simple fasta-formatted file as input, Cis SERS utilizes the REBASE enzyme database. Results from Cis SERSenable the user to make decisions for designing genotyping by sequencing experiments, reduced representation sequencing, 3’UTR sequencing, and cleaved amplified polymorphic sequence (CAPS) molecular markers for large sample sets. Cis SERS is a java based graphical user interface built around a perl backbone. Several of the applications of Cis SERS including CAPS molecular marker development were successfully validated using wet-lab experimentation. Here, we present the tool Cis SERSand results from in-silico and corresponding wet-lab analyses demonstrating that Cis SERS is a technology platform solution that facilitates efficient data utilization in genomics and genetics studies.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2017

Variations of five eIF4E genes across cassava accessions exhibiting tolerant and susceptible responses to cassava brown streak disease

Cassava (Manihot esculenta) is an important tropical subsistence crop that is severely affected by cassava brown streak disease (CBSD) in East Africa. The disease is caused by Cassava brown streak virus (CBSV) and Ugandan cassava brown streak virus (UCBSV). Both have a (+)-sense single-stranded RNA genome with a 5’ covalently-linked viral protein, which functionally resembles the cap structure of mRNA, binds to eukaryotic translation initiation factor 4E (eIF4E) or its analogues, and then enable the translation of viral genomic RNA in host cells. To characterize cassava eIF4Es and their potential role in CBSD tolerance and susceptibility, we cloned five eIF4E transcripts from cassava (accession TMS60444). Sequence analysis indicated that the cassava eIF4E family of proteins consisted of one eIF4E, two eIF(iso)4E, and two divergent copies of novel cap-binding proteins (nCBPs). Our data demonstrated experimentally the coding of these five genes as annotated in the published cassava genome and provided additional evidence for refined annotations. Illumina resequencing data of the five eIF4E genes were analyzed from 14 cassava lines tolerant or susceptible to CBSD. Abundant single nucleotide polymorphisms (SNP) and biallelic variations were observed in the eIF4E genes; however, most of the SNPs were located in the introns and non-coding regions of the exons. Association studies of non-synonymous SNPs revealed no significant association between any SNP of the five eIF4E genes and the tolerance or susceptibility to CBSD. However, two SNPs in two genes were weakly associated with the CBSD responses but had no direct causal-effect relationship. SNPs in an intergenic region upstream of eIF4E_me showed a surprising strong association with CBSD responses. Digital expression profile analysis showed differential expression of different eIF4E genes but no significant difference in gene expression was found between susceptible and tolerant cassava accessions despite the association of the intergenic SNPs with CBSD responses.

59 BASIC BIOLOGICAL SCIENCES↗