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At least 559 records · Page 31
All sourcesNASA NTRSDOE OSTI
DOE OSTI2022

Lactiplantibacillus plantarum 0111 Protects Against Influenza Virus by Modulating Intestinal Microbial-Mediated Immune Responses

There are some limitations of traditional influenza vaccines concerning novel mutant strains. Therefore, it is particularly important to develop preventive means for antigen-unrelated types of influenza viruses. Recent studies have shown that probiotics can modulate the immune system and reduce the severity of viral infections. In this study, we investigated the potential of Lactiplantibacillus plantarum 0111 against influenza virus H9N2. Challenge experiments showed that L. plantarum 0111 pretreatments could effectively improve mice’s survival rate and weight loss and reduce the inflammatory cytokines IL-6 and TNF-α in the lungs and bronchoalveolar lavage fluid (BALF) along with the degree of lung and intestinal injury. FMT experiment demonstrates that the protective effect produced by L. plantarum 0111 is associated with gut microorganisms. In addition, 16S high-throughput sequencing of the mouse intestinal microbiota showed that L. plantarum 0111 remodeled the intestinal microbiota after H9N2 infection and maintained the gut microbiota balance. In a mouse model, the oral administration of L. plantarum 0111 increased IFN-β expression in the serum and BALF. At the same time, the transcript levels of IFN-β and related ISGs in the intestine and lungs of mice were also increased. In addition, the activation and polarization of T cells in mesenteric lymph nodes (MLNs) and the spleen were detected by flow cytometry, and the results showed that L. plantarum 0111 modulated cytokines in T cells and increased IgA expression in B cells in the MLNs and spleen. Thus, L. plantarum 0111 may improve gut microbiota-mediated immune responses and thus, resist infection by the influenza virus, and it could be used as an effective preventive measure against the influenza virus.

Xing, Jun-Hong↗
DOE OSTI2023

Differential transcriptomic alterations in nasal versus lung tissue of acrolein-exposed rats

Introduction: Acrolein is a significant component of anthropogenic and wildfire emissions, as well as cigarette smoke. Although acrolein primarily deposits in the upper respiratory tract upon inhalation, patterns of site-specific injury in nasal versus pulmonary tissues are not well characterized. This assessment is critical in the design of in vitro and in vivo studies performed for assessing health risk of irritant air pollutants. Methods: In this study, male and female Wistar-Kyoto rats were exposed nose-only to air or acrolein. Rats in the acrolein exposure group were exposed to incremental concentrations of acrolein (0, 0.1, 0.316, 1 ppm) for the first 30 min, followed by a 3.5 h exposure at 3.16 ppm. In the first cohort of male and female rats, nasal and bronchoalveolar lavage fluids were analyzed for markers of inflammation, and in a second cohort of males, nasal airway and left lung tissues were used for mRNA sequencing. Results: Protein leakage in nasal airways of acrolein-exposed rats was similar in both sexes; however, inflammatory cells and cytokine increases were more pronounced in males when compared to females. No consistent changes were noted in bronchoalveolar lavage fluid of males or females except for increases in total cells and IL-6. Acrolein-exposed male rats had 452 differentially expressed genes (DEGs) in nasal tissue versus only 95 in the lung. Pathway analysis of DEGs in the nose indicated acute phase response signaling, Nrf2-mediated oxidative stress, unfolded protein response, and other inflammatory pathways, whereas in the lung, xenobiotic metabolism pathways were changed. Genes associated with glucocorticoid and GPCR signaling were also changed in the nose but not in the lung. Discussion: These data provide insights into inhaled acrolein-mediated sex-specific injury/inflammation in the nasal and pulmonary airways. The transcriptional response in the nose reflects acrolein-induced acute oxidative and cytokine signaling changes, which might have implications for upper airway inflammatory disease susceptibility.

Alewel, Devin I.↗
DOE OSTI2021

Electrodeposition of Aluminum in the 1-Ethyl-3-Methylimidazolium Tetrachloroaluminate Ionic Liquid

The electrodeposition of Al was investigated in an ionic liquid (IL), with 1-ethyl-3-methylimidazolium tetrachloroaluminate ([EMIm]AlCl4) as the electrolyte with AlCl3 precursor. The [EMIm]AlCl4 electrolyte exhibited a wide and stable electrochemical window from 3.2 to 2.3 V on a glassy carbon electrode when temperature was increased from 30 °C to 110 °C. The addition of AlCl3 into [EMIm]AlCl4 generated significant well-developed nucleation growth loops, and new coupled reduction and oxidation peaks in cyclic voltammograms corresponding to the Al deposition and dissolution, respectively. A calculation model was proposed predicting compositions of anions in AlCl3/[EMIm]AlCl4 system, and [Al2Cl7]− was found to be the active species for Al deposition. In AlCl3/[EMIm]AlCl4 (1:5), the reduction rate constants were 1.18 × 10−5 cm s−1 and 3.37 × 10−4 cm s−1 at 30 °C and 110 °C, respectively. Scanning electron microscope (SEM), energy dispersive spectroscope (EDS), and X-ray diffraction (XRD) microscope results showed that the metallic Al film had been successfully deposited on glassy carbon electrodes through constant-potential cathodic reductions. The [EMIm]AlCl4 was a promising electrolyte directly used for Al deposition.

Shi, Meng↗
DOE OSTI2022

Early Immune Modulation in European Seabass (Dicentrarchus labrax) Juveniles in Response to Betanodavirus Infection

The early host–pathogen interaction between European seabass (Dicentrarchus labrax) and Betanodavirus was examined by using juvenile fish infected intramuscularly with RGNNV (red-spotted grouper nervous necrosis virus). The time course selected for sampling (0–144 h post-infection (hpi)) covered the early stages of infection, with hematological, antioxidant and immunological responses examined. Early activation of the host’s immune system was seen in the first few hours post-infection (6 to 9 hpi), as evidenced by an increase in tnfα, cd28 and c3 expression in the head kidney of infected fish. Most hematological parameters that were examined showed significant differences between sampling times, including differences in the number of thrombocytes and various leukocyte populations. The plasma lysozyme concentration decreased significantly over the course of the trial, and most antioxidant parameters examined in the liver showed significant differences over the infection period. At 144 hpi, peak expression of tnfα and il-1β coincided with the appearance of disease symptoms, peak levels of virus in the brain and high levels of fish mortality. The results of the study show the importance of analyzing the early interactions between European seabass and Betanodavirus to establish early indicators of infection to prevent more severe outcomes of the infection from occurring.

Vaz, Mariana↗
DOE OSTI2021

Sclerostin Depletion Induces Inflammation in the Bone Marrow of Mice

Romosozumab, a humanized monoclonal antibody specific for sclerostin (SOST), has been approved for treatment of postmenopausal women with osteoporosis at a high risk for fracture. Previous work in sclerostin global knockout (Sost-/- ) mice indicated alterations in immune cell development in the bone marrow (BM), which could be a possible side effect in romosozumab-treated patients. Here, we examined the effects of short-term sclerostin depletion in the BM on hematopoiesis in young mice receiving sclerostin antibody (Scl-Ab) treatment for 6 weeks, and the effects of long-term Sost deficiency on wild-type (WT) long-term hematopoietic stem cells transplanted into older cohorts of Sost-/- mice. Our analyses revealed an increased frequency of granulocytes in the BM of Scl-Ab-treated mice and WT→Sost -/- chimeras, indicating myeloid-biased differentiation in Sost-deficient BM microenvironments. This myeloid bias extended to extramedullary hematopoiesis in the spleen and was correlated with an increase in inflammatory cytokines TNFα, IL-1α, and MCP-1 in Sost-/- BM serum. Additionally, we observed alterations in erythrocyte differentiation in the BM and spleen of Sost-/- mice. Taken together, our current study indicates novel roles for Sost in the regulation of myelopoiesis and control of inflammation in the BM.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2020

Synthesis and Performance of Aromatic Polyamide Ionenes as Gas Separation Membranes

Here, we report the synthesis and thermophysical properties of seven primarily aromatic, imidazolium-based polyamide ionenes. The effects of varied para-, meta-, and ortho-connectivity, and spacing of ionic and amide functional groups, on structural and thermophysical properties were analyzed. Suitable, robust derivatives were cast into thin films, neat, or with stoichiometric equivalents of the ionic liquid (IL) 1-benzy-3-methylimidazolium bistriflimide ([Bnmim][Tf 2 N]), and the gas transport properties of these membranes were measured. Pure gas permeabilities and permselectivities for N 2 , CH 4 , and CO 2 are reported. Consistent para-connectivity in the backbone was shown to yield the highest CO 2 permeability and suitability for casting as a very thin, flexible film. Derivatives containing terephthalamide segments exhibited the highest CO 2 /CH 4 and CO 2 /N 2 selectivities, yet CO 2 permeability decreased with further deviation from consistent para-linkages.

36 MATERIALS SCIENCE↗
DOE OSTI2023

Dissecting Phenotype from Genotype with Clinical Isolates of SARS-CoV-2 First Wave Variants

The emergence and availability of closely related clinical isolates of SARS-CoV-2 offers a unique opportunity to identify novel nonsynonymous mutations that may impact phenotype. Global sequencing efforts show that SARS-CoV-2 variants have emerged and then been replaced since the beginning of the pandemic, yet we have limited information regarding the breadth of variant-specific host responses. Using primary cell cultures and the K18-hACE2 mouse, we investigated the replication, innate immune response, and pathology of closely related, clinical variants circulating during the first wave of the pandemic. Mathematical modeling of the lung viral replication of four clinical isolates showed a dichotomy between two B.1. isolates with significantly faster and slower infected cell clearance rates, respectively. While isolates induced several common immune host responses to infection, one B.1 isolate was unique in the promotion of eosinophil-associated proteins IL-5 and CCL11. Moreover, its mortality rate was significantly slower. Lung microscopic histopathology suggested further phenotypic divergence among the five isolates showing three distinct sets of phenotypes: (i) consolidation, alveolar hemorrhage, and inflammation, (ii) interstitial inflammation/septal thickening and peribronchiolar/perivascular lymphoid cells, and (iii) consolidation, alveolar involvement, and endothelial hypertrophy/margination. Together these findings show divergence in the phenotypic outcomes of these clinical isolates and reveal the potential importance of nonsynonymous mutations in nsp2 and ORF8.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2024

Pathogenic and Apathogenic Strains of Lymphocytic Choriomeningitis Virus Have Distinct Entry and Innate Immune Activation Pathways

Lymphocytic choriomeningitis virus (LCMV) and Lassa virus (LASV) share many genetic and biological features including subtle differences between pathogenic and apathogenic strains. Despite remarkable genetic similarity, the viscerotropic WE strain of LCMV causes a fatal LASV fever-like hepatitis in non-human primates (NHPs) while the mouse-adapted Armstrong (ARM) strain of LCMV is deeply attenuated in NHPs and can vaccinate against LCMV-WE challenge. Here, we demonstrate that internalization of WE is more sensitive to the depletion of membrane cholesterol than ARM infection while ARM infection is more reliant on endosomal acidification. LCMV-ARM induces robust NF-κB and interferon response factor (IRF) activation while LCMV-WE seems to avoid early innate sensing and failed to induce strong NF-κB and IRF responses in dual-reporter monocyte and epithelial cells. Toll-like receptor 2 (TLR-2) signaling appears to play a critical role in NF-κB activation and the silencing of TLR-2 shuts down IL-6 production in ARM but not in WE-infected cells. Pathogenic LCMV-WE infection is poorly recognized in early endosomes and failed to induce TLR-2/Mal-dependent pro-inflammatory cytokines. Following infection, Interleukin-1 receptor-associated kinase 1 (IRAK-1) expression is diminished in LCMV-ARM- but not LCMV-WE-infected cells, which indicates it is likely involved in the LCMV-ARM NF-κB activation. By confocal microscopy, ARM and WE strains have similar intracellular trafficking although LCMV-ARM infection appears to coincide with greater co-localization of early endosome marker EEA1 with TLR-2. Both strains co-localize with Rab-7, a late endosome marker, but the interaction with LCMV-WE seems to be more prolonged. These findings suggest that LCMV-ARM’s intracellular trafficking pathway may facilitate interaction with innate immune sensors, which promotes the induction of effective innate and adaptive immune responses.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2026

Impact of Selenium and Vitamin E Deficiency on Zika Virus Pathogenesis and Immune Response in Mice

Micronutrient status is recognized to influence host susceptibility to viral infections, yet its impact on Zika virus (ZIKV) pathogenesis remains incompletely understood. We investigated the effects of dietary selenium and combined selenium plus vitamin E deficiency on ZIKV infection outcomes in a type I interferon α/β receptor knockout (Ifnar1 −/− ) murine model. Mice maintained on deficient diets exhibited significantly lower neutralizing antibody titers and reduced levels of key antiviral cytokines (IFN-γ, TNF-α, IFN-α, IFN-β, IL-12p70, CCL5) compared to controls. Correspondingly, higher viral RNA loads were detected in the brains of double-deficient mice, which also experienced greater weight loss and increased mortality. Deep sequencing revealed no major differences in overall viral genome diversity across diet groups; however, specific mutations, including V330L and D67E in the E gene, and V360I in the NS3 gene, were enriched or detected in nutritionally deficient animals. These findings suggest that antioxidant micronutrient deficiency impairs both humoral and cellular immune responses to ZIKV, potentially facilitating enhanced neuroinvasion. While the functional consequences of the identified mutations warrant further investigation, our results underscore the importance of adequate micronutrient intake for optimal antiviral defense. Further studies are needed to clarify the epidemiological significance of these observations.

Biological and medical sciences↗
DOE OSTI2021

First Muon Neutrino on Argon Cross Section Measurements With an Off-Axis Beam

While over ninety years have passed since neutrinos were first predicted in 1930 by Wolfgang Pauli, much about them is still unknown [20]. How many types of neutrinos there are, how precisely neutrinos change flavor, and how neutrinos interact with various types of matter are largely unanswered questions that have implications for fields beyond particle physics, such as cosmology and astrophysics. The final question can be answered partially by differential cross section measurements, two of which constitute the primary result of this thesis. The NeUtrinos at the Main Injector (NuMI) Beam at Fermilab in Batavia, IL provides a source of muon neutrinos and muon antineutrinos to the MicroBooNE experiment, an 85 ton liquid argon time projection chamber (LArTPC). The technology allows for high precision particle tracking and energy reconstruction that can be used to make cross section measurements. Necessary work for making these measurements for which the author of this thesis made an essential contribution is presented in detail in References [21] [22] [11] [23]. The measurement presented in this thesis is made with 2.187e20 Protons on Target (POT), the standard metric for an amount of beam exposure, of data when the beam was in forward horn current mode. Single-differential cross section measurements in terms of muon candidate kinetic energy and direction are made, and their statistical fits with simulation are 5.8 (12 d.o.f.) and 11.4 (10 d.o.f.), respectively. This indicates that the muon kinematics for muon neutrino and muon antineutrino charged-current (CC) events primarily in the energy range [0-3] GeV can be trusted for oscillation experiments, including DUNE, because of the agreement to within the associated systematic and statistical uncertainties between the measurement and the model in every bin of both single-differential cross sections. This result adds to the corresponding result for the Booster Neutrino Beam (BNB) because it covers a completely different energy region than that measurement, a double-differential cross section in terms of muon momentum and direction [14]. This result contributes to reducing the uncertainty in near-far event rate comparisons in long baseline neutrino experiments and also adds to existing knowledge of the neutrino-nucleus interaction by describing the outgoing muon kinematics in interactions of muon neutrinos and muon antineutrinos. This result is the first-ever measurement of differential cross sections of muon neutrinos and muon antineutrinos in liquid argon made with an off-axis beam.

72 PHYSICS OF ELEMENTARY PARTICLES AND FIELDS↗
DOE OSTI2021

Quantile-dependent expressivity of serum C-reactive protein concentrations in family sets

“Quantile-dependent expressivity” occurs when the effect size of a genetic variant depends upon whether the phenotype (e.g., C-reactive protein, CRP) is high or low relative to its distribution. We have previously shown that the heritabilities ( h 2 ) of coffee and alcohol consumption, postprandial lipemia, lipoproteins, leptin, adiponectin, adiposity, and pulmonary function are quantile-specific. Whether CRP heritability is quantile-specific is currently unknown. Methods Serum CRP concentrations from 2,036 sibships and 6,144 offspring-parent pairs were analyzed from the Framingham Heart Study. Quantile-specific heritability from full-sib (β FS , h 2 ={(1 + 8r spouse β FS ) 0.5 - 1}/(2r spouse )) and offspring-parent regression slopes (β OP , h 2 = 2β OP /(1 + r spouse )) were estimated robustly by quantile regression with nonparametric significance determined from 1,000 bootstrap samples. Results Quantile-specific h 2 (±SE) increased with increasing percentiles of the offspring’s age- and sex-adjusted CRP distribution when estimated from β OP ( P trend = 0.0004): 0.02 ± 0.01 at the 10th, 0.04 ± 0.01 at the 25th, 0.10 ± 0.02 at the 50th, 0.20 ± 0.05 at the 75th, and 0.33 ± 0.10 at the 90th percentile, and when estimated from β FS ( P trend = 0.0008): 0.03±0.01 at the 10th, 0.06 ± 0.02 at the 25th, 0.14 ± 0.03 at the 50th, 0.24 ± 0.05 at the 75th, and 0.53 ± 0.21 at the 90th percentile. Conclusion Heritability of serum CRP concentration is quantile-specific, which may explain or contribute to the inflated CRP differences between CRP (rs1130864, rs1205, rs1800947, rs2794521, rs3091244), FGB (rs1800787), IL-6 (rs1800795, rs1800796), IL6R (rs8192284), TNF- α (rs1800629) and APOE genotypes following CABG surgery, stroke, TIA, curative esophagectomy, intensive periodontal therapy, or acute exercise; during acute coronary syndrome or Staphylococcus aureus bacteremia; or in patients with chronic rheumatoid arthritis, diabetes, peripheral arterial disease, ankylosing spondylitis, obesity or inflammatory bowel disease or who smoke.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2020

An advanced membrane-based HMX model and its application in utilizing sensible and latent heat removed in space cooling

This paper presents a comprehensive simulation model for advanced membrane-based heat and mass exchanger (HMX) components which account for three separate fluid streams with complex flow patterns. The model was implemented with various liquid desiccants and their properties (including LiCl, CaCl and ionic liquid (IL)). Preliminary model validation is presented using data from a laboratory prototype absorber. The paper also presents implementation of the model into a sorption system modeling platform and analyzes potential benefit analysis of the HMX component in utilizing the sensible and latent heat removed in space cooling to heat water. The developed model and codes are expected to enable detailed optimization studies and identify novel configurations for the three-fluid HMX maximum performance and cost effectiveness.

Gao, Zhiming↗
DOE OSTI2020

Hadronic contributions to (g - 2) µ

The Muon g-2 Experiment at Fermilab, which recently started running, plans to reduce the uncertain- ties on the already very precisely measured anomalous magnetic moment of the muon by a factor of four. The goal of this effort is to probe the observed difference of more than three standard deviations between Standard-Model theory and experiment, one of the few persistent hints for physics beyond the Standard Model. The Fermilab experiment collected data from their first run last year with statistics comparable to BNL E821. They expect to release the measurement result in 2019. On the theoretical side, because the muon g - 2 arises from quantum- mechanical loop contributions in the Standard Model, it is sensitive to virtual effects of new particles, and places important constraints on Standard-Model extensions. To leverage the anticipated reduction in experimental errors, and determine unambiguously whether or not new-physics effects contribute to this quantity, the theoretical errors must be made more reliable and reduced to a commensurate precision. The Muon g-2 Theory Initiative was created to facilitate this development. The dominant sources of uncertainty in the Standard-Model prediction of the muon g -2 are from the hadronic contributions. The hadronic vacuum polarization (HVP) provides the leading correction followed by hadronic light-by-light (HLbL) scattering. There are a number of complementary theoretical efforts underway to better understand and quantify these contributions, including dispersive and data driven methods, lattice QCD, and effective field theories. Given the precision goals and the phenomenological importance, it is important to have more than one independent method for each of the two hadronic corrections, each with fully quantified uncertainties. Fostering the development of such methods is a prime goal of the initiative, as this will enable critical cross checks, and, upon combination, may yield gains in precision, to maximize the impact of E989. An important aspect of the Muon g-2 Theory Initiative’s activities are providing platforms that facilitate interactions between the different groups, as well as between the theoretical and experimental g - 2 communities. To this end, several workshops were organized in 2017 and 2018. The first meeting, held at Fermilab (June 3–6, 2017, St. Charles, IL, USA), served to kick-off the Initiative’s activities. Two meetings in early 2018 were focused respectively on the HVP and HLbL corrections. The HVP meeting was held at KEK (February 12–14, 2018, Tsukuba, Japan) and the HLbL meeting at the University of Connecticut (March 12–14, 2018, Storrs, CT, USA). The most recent workshop, which served as the second plenary meeting of the Initiative, was held at the University of Mainz (June 18–22, 2018, Mainz, Germany). An important outcome of these meetings are concrete plans for a first white paper, which is currently being written. We aim to post the white paper just prior to the release of the first E989 measurement, to present a clean theoretical prediction. The first white paper is focused on assessing and improving the reliability of the SM prediction. The purpose of the INT workshop in September 2019 is to start the next stage of the Initiative, focusing on the development of strategies to improve the theory uncertainties beyond the current level towards the E989 precision goal. We aim to accelerate theoretical developments on the hadronic contributions to the muon g - 2 so that the Standard-Model theory error can be brought to the needed precision, again in advance of the next release from E989. Hence the workshop will provide crucial theory support for a US experiment with broad impact. The Muon g-2 Theory Initiative relies on input from representatives of all the different communities that are engaged in this effort. It is therefore important that all these areas are properly represented. The funds from this grant will be used to enable more people, especially early-career scientists, to participate and make essential contributions to the workshop discussions. Since the workshop’s main goal is to kick-off the next stage of the theory initiative’s activities, support for this workshop from the DOE will help the theory community provide crucial theoretical support to the Fermilab Muon g-2 Experiment.

72 PHYSICS OF ELEMENTARY PARTICLES AND FIELDS↗
DOE OSTI2020

Characterization of Mechanical Ventilation Systems in New US Homes: What types of systems are out there and are they functioning as intended?

As the airtightness of homes improves to meet energy efficiency goals, it becomes more important for mechanical ventilation systems to help maintain a comfortable and healthy indoor air environment. ASHRAE Standard 62.2 provides national guidance for mechanical ventilation system design and installation, however adoption of those guidelines into local building codes has occurred at different rates. Once provisions for mechanical ventilation are adopted in a local code, are mechanical ventilation systems properly designed, installed, commissioned and operated according to code or above code program requirements? Is there a need for further industry and homeowner education to ensure systems function as intended? This paper presents results from field studies that include characterization of mechanical ventilation systems in over 150 new homes in CA, CO, FL, GA, IL, OR, and SC built between 2011 and 2018. In each of the study homes, airflow of local (kitchen, bathrooms) and whole-house ventilation were measured. Occupant usage of the mechanical ventilation systems were monitored for one week in each home. Installed performance is compared to inferred design intent. The paper also includes homeowner perceptions about, and interactions with, the installed mechanical ventilation systems.

Martin, Eric↗
DOE OSTI2021

A-scaling of CCQE-like cross sections at MINERvA

MINERvA is a precision cross section experiment for neutrino scattering processes located at Fermilab in Batavia, IL. MINERvA has carbon, water, iron and lead nuclear targets to measure the A-scaling of cross sections. Using those targets, this analysis measures the CCQE-like cross sections on the different targets. The CCQE-like cross section is a measure of the probability that a neutrino interactionproduces an event with a muon, any number of nucleons and no mesons (such as pions). The cross sections are measured in 2-dimensional muon momentum space as well as using the so-called Transverse Kinematic Variables (TKI) which combine muon and proton variables. These variables are sensitive to various nuclear effects. Presented in this thesis are MINERvA’s first 2-dimensional results in the nuclear targets, MINERvA’s first TKI results in the nuclear targets and MINERvA’s first result using its water target.

Kleykamp, Jeffrey↗
DOE OSTI2022

A New Search for Low-mass Dark Matter and an Examination and Reduction of the Uncertainty due to the Photoelectric Absorption Cross Section using a Cryogenic Silicon Detector with Single-charge Sensitivity

Many astrophysical observations point to the abundant existence of dark matter (DM) in the universe composed of particles beyond the Standard Model. However despite numerous experiments using different techniques, DM particles have yet to be directly observed. The Super Cryogenic Dark Matter Search (SuperCDMS) SNOLAB experiment will employ silicon and germanium crystal detectors operated at temperatures as low as 15~mK to probe DM interactions using phonon and ionization signals. Recently, R\&D; facilities have developed gram-sized high-voltage eV-scale (HVeV) silicon detectors that achieve single-electron-hole-pair resolution. By probing effective DM-electron interactions, these devices can be used for searches of low-mass DM candidates.This dissertation presents a DM search experiment known as HVeV Run~2 that employs a second-generation HVeV detector operated in an above-ground laboratory at Northwestern University (IL, USA). Energy spectra are obtained from a blind analysis with 0.39 and 1.2\,g-days of exposure with the detector biased at 60 and 100\,V, respectively. The 0.93~gram detector achieves a 3\,eV phonon energy resolution, corresponding to a world-leading charge resolution of 3\,\% of a single electron-hole pair for a detector bias of 100\,V. With charge carrier trapping and impact ionization effects incorporated into the DM signal models, the resulting exclusion limits are reported for inelastic DM-electron scattering for DM masses from 0.5--$10^{4}$\,MeV$/c^{2}$; in the mass range from 1.2--50\,eV$/c^{2}$ the limits for dark photon and axion-like particle absorption are reported.Several DM search experiments, including HVeV Run~2, are sensitive to low-mass DM candidates that rely on the temperature-dependent photoelectric absorption cross section of silicon. However discrepancies in the underlying literature data result in dominating systematic uncertainties on the DM exclusion limits. In order to reduce these systematic uncertainties, this dissertation presents a novel method of making a direct, low-temperature measurement of the photoelectric absorption cross section of silicon at energies near the band gap (1.2--2.8\,eV).

Wilson, Matthew James↗