Los Alamos Research Articles

Variability of non-structural proteins of HIV-1 sub-subtype A6 (Retroviridae: Orthoretrovirinae: Lentivirus: Human immunodeficiency virus-1, sub-subtype A6) variants circulating in different regions of the Russian Federation.

HIV-1 non-structural proteins are promising targets for vaccine development and for creating approaches to personalized medicine. HIV-1 sub-subtype A6 has become the dominating strain in Russia. However, the geographic, economic and demographic characteristics of the country can contribute to the formation of differences between A6 variants circulating in different regions. The aim of the study is a comparative analysis of the consensus sequences of non-structural proteins in A6 variants circulating in the Amur Region, in Arkhangelsk, Irkutsk and Murmansk. 48 whole blood samples obtained from HIV-infected patients without experience of therapy observed at the AIDS Centers in Arkhangelsk, Irkutsk, Murmansk and Amur Region were analyzed. HIV-1 whole-genome nucleotide sequences were obtained and were subtyped. Consensus sequences of sub-subtype A6 variants non-structural proteins for each analyzed region were formed. Furthermore, reference sequences of sub-subtype A6 non-structural proteins were formed based on whole-genome sequences retrieved from the international Los Alamos database. Comparison of consensus sequences and references was performed using the MEGA v.10.2.2 and the PSIPRED programs. Vif, Vpr and Nef reference sequences have been obtained for HIV-1 sub-subtype A6. There was not difference in consensus sequences of Vpr in different regions. Characteristic features were found for consensus sequences of Tat, Rev, Vpu, Vif and Nef proteins in different regions. A limitation of the study is a small sample size. Overall, the results demonstrate the existing diversity of non-structural proteins in sub-subtype A6 variants in different regions and indicate the relevance of studying the polymorphism of non-structural proteins of virus variants in different regions.

Prediction and observation of regional infrasound from the OSIRIS REx re-entry capsule

Infrasonic signals produced by bolides and space debris passing through atmosphere are frequently observed at notable stand-off distances. The acoustic energy radiated from such objects is dominated by the aero-acoustic Mach cone which exhibits a highly directional radiation pattern dependent on the velocity of the object relative to the surrounding atmosphere. Recently, a mapping of the Mach cone geometry into acoustic ray tracing methods has enabled efficient regional simulation of infrasonic ensonification from such sources. In September 2023, the OSIRIS REx sample capsule returned to Earth as part of a NASA supported asteroid study and a number of institutions deployed sensors to measure geophysical signatures of the event. The anticipated capsule trajectory was combined with historical atmospheric data for September in the western United States to predict likely regional ensonification during re-entry. Los Alamos National Laboratory infrasound experts deployed microbarometer arrays in locations predicted to be ensonified and were able to identify signals with arrival times and direction-of-arrival consistent with the capsule re-entry. An overview of the predictions, field deployments, and identified signals will be presented.

ExaFEL: extreme-scale real-time data processing for X-ray free electron laser science

ExaFEL is an HPC-capable X-ray Free Electron Laser (XFEL) data analysis software suite for both Serial Femtosecond Crystallography (SFX) and Single Particle Imaging (SPI) developed in collaboration with the Linac Coherent Lightsource (LCLS), Lawrence Berkeley National Laboratory (LBNL) and Los Alamos National Laboratory. ExaFEL supports real-time data analysis via a cross-facility workflow spanning LCLS and HPC centers such as NERSC and OLCF. Our work therefore constitutes initial path-finding for the US Department of Energy's (DOE) Integrated Research Infrastructure (IRI) program. We present the ExaFEL team's 7 years of experience in developing real-time XFEL data analysis software for the DOE's exascale supercomputers. We present our experiences and lessons learned with the Perlmutter and Frontier supercomputers. Furthermore we outline essential data center services (and the implications for institutional policy) required for real-time data analysis. Finally we summarize our software and performance engineering approaches and our experiences with NERSC's Perlmutter and OLCF's Frontier systems. This work is intended to be a practical blueprint for similar efforts in integrating exascale compute resources into other cross-facility workflows.

Low Energy Neutron-induced Charged-particle (Z) (LENZ) instrument development with a focus on pulse shape discrimination for low-energy charged particles

To study neutron-induced charged-particle reactions with high precision, the Low Energy Neutron-induced Charged-particle (Z) instrument (LENZ) was developed at the Los Alamos Neutron Science Center. For the interest of measuring (n,p) and (n, α) reactions simultaneously, Pulse Shape Discrimination methods were investigated to identify different charged particles in the energy range of 3 - 20 MeV and improve signal-to-background ratios using Double-sided Silicon Strip Detectors and waveform digitizers. The risetime and pulse shape properties of detected charged particles were characterized for various silicon detector’s thickness with different orientations. During the post-processing of waveforms, we implemented different digital filters for effective particle identifications and improved energy- and timing- resolutions. We validated the optimized digital filters and pulse shape analyses, via measurements with 228Th and 229Th calibration sources, proton-induced reactions on a 7LiF target, and neutron-induced reactions on CH2, Ta2O5, 58Ni, and 6LiF/59Ni targets at the time-of-flight facility, LANSCE. The summary of effective thresholds and Figure of Merits on separating different charged particles is reported.

Heisenberg's 1939 reactor theory, Serber's 1943 Los Alamos Primer, and Heisenberg's 1945 Farm Hall critical mass calculation

Heisenberg's 1939 reactor theory, Serber's 1943 Los Alamos Primer, and Heisenberg's 1945 Farm Hall critical mass calculation

Cerium doped yttrium aluminum perovskite scintillator as an absolute ultracold neutron detector.

The upcoming UCNProBe experiment at Los Alamos National Laboratory will measure the beta decay rate of free neutrons with different systematic uncertainties than previous beam-based neutron lifetime experiments. We have tested a new 10B-coated Yttrium Aluminum Perovskite (YAP:Ce) scintillator and present its properties. The advantages of the YAP:Ce scintillator include its high Fermi potential, which reduces the probability for upscattering of ultracold neutrons (UCN), and its short decay time, which increases sensitivity at high counting rates. Birks' coefficient of YAP:Ce was measured to be (5.56-0.30+0.05)×10-4 cm/MeV. The loss of light due to the 120nm 10B-coating was measured to be about 60%, and the loss of light from YAP:Ce due to transmission through a deuterated polystyrene scintillator was about 50%. The efficiency for neutron capture on the 10B coating was (86.8 ± 2.6)%, and a measurement using UCN showed that the YAP:Ce crystal counted 8%-28% more UCN compared to a ZnS:Ag screen. The difference may be due to the uneven coating of 10B on the rough surface of ZnS:Ag.

PreMevE‐MEO: Predicting Ultra‐Relativistic Electrons Using Observations From GPS Satellites

AbstractUltra‐relativistic electrons with energies greater than or equal to two megaelectron‐volt (MeV) pose a major radiation threat to spaceborne electronics, and thus specifying those highly energetic electrons has a significant meaning to space weather communities. Here we report the latest progress in developing our predictive model for MeV electrons in the outer radiation belt. The new version, primarily driven by electron measurements made along medium‐Earth‐orbits (MEO), is called PREdictive MEV Electron (PreMevE)‐MEO model that nowcasts ultra‐relativistic electron flux distributions across the whole outer belt. Model inputs include >2 MeV electron fluxes observed in MEOs by a fleet of GPS satellites as well as electrons measured by one Los Alamos satellite in the geosynchronous orbit. We developed an innovative Sparse Multi‐Inputs Latent Ensemble NETwork (SmileNet) which combines convolutional neural networks with transformers, and we used long‐term in situ electron data from NASA's Van Allen Probes mission to train, validate, optimize, and test the model. It is shown that PreMevE‐MEO can provide hourly nowcasts with high model performance efficiency and high correlation with observations. This prototype PreMevE‐MEO model demonstrates the feasibility of making high‐fidelity predictions driven by observations from longstanding space infrastructure in MEO, thus has great potential of growing into an invaluable space weather operational warning tool.

Speciation and formation constants of aqueous lanthanum (III) chloride complexes from 5 to 80 °C by Raman spectroscopy

Lanthanum chloride solutions were studied both computationally and by polarized Raman spectroscopy to determine the aqueous species present and their equilibrium constants. Four species were predicted from Gaussian 16 computations using density functional theory: La(H2O)9 3+, LaCl(H2O)8 2+, LaCl2(H2O)6 2+, and LaCl3(H2O)4 0. Both LaCl(H2O)8 2+ and LaCl2(H2O)6 + were identified in the reduced isotropic solvent-subtracted Raman spectra from their La–Cl vibrational bands at 234 and 221 cm−1, respectively. The spectra did not change significantly with temperature from 5 to 80 °C, and the Raman bands for each species could not be fitted with sufficient accuracy to determine the scattering coefficients directly from the experimental data. Instead, the computed scattering coefficients from Gaussian 16 (B3LYP with the Los Alamos National Laboratory 2-double-zeta effective core potential and 6-311+G(d,p) basis set) were to be used to obtain the equilibrium concentrations of LaCl(H2O)8 2+ and LaCl2(H2O)6 +, from which the concentration of La(H2O)9 3+ was determined. The concentration dependent formation quotients were fitted with the specific ion interaction (SIT) activity coefficient model to determine the stepwise formation constants K0, 1 and K1, 2, from 5 to 80 °C. Both K0, 1 and K1, 2 showed minor increases with temperature.

Development of a total variation diminishing (TVD) sea ice transport scheme and its application in an ocean (SCHISM v5.11) and sea ice (Icepack v1.3.4) coupled model on unstructured grids

Abstract. As the demand for increased resolution and complexity in unstructured sea ice models is growing, higher demands are also placed on the sea ice transport scheme. In this study, we couple the Semi-implicit Cross-scale Hydro-science Integrated System Model (SCHISM, v5.11) with Icepack (v1.3.4), the column physics package of the Los Alamos sea ice model (CICE); a key step is to implement a total variation diminishing (TVD) transport scheme for the multi-class sea ice module in the coupled model. Compared with the second-order upwind scheme and the finite-element flux-corrected transport (FEM-FCT) scheme, the TVD transport scheme is overall superior when evaluated based on conservation, accuracy, efficiency (even with very high resolution), and strict monotonicity. Although it is slightly weaker than FEM-FCT in terms of accuracy alone, the TVD scheme still outperforms the other two schemes in comprehensive performance. The new coupled model outperforms the existing single-class ice model of SCHISM in the case of Lake Superior. For the Arctic Ocean case, it successfully reproduces the long-term changes in the sea ice extent, sea ice boundary, concentration observations from satellites, and thickness from in situ measurement.

Multiphysics analysis of mechanical responses in micro-reactors under varied operating conditions

Micro-reactors are a promising alternative for power production applications where traditional methods may not be feasible (e.g., space missions). Their design requires critical selection of materials, especially for moderator and fuel, to ensure long-term operation and optimal performance. This research focuses on developing computational analysis models for micro-reactors, aiming to explore their structural behavior under thermal and mechanical loadings. The micro-reactor model is based on the Zero Energy Breeder Reactor Assembly (Zebra) Kilowatt (kW) reactor design conceptualized at Los Alamos National Laboratory. This study investigates the thermal and mechanical responses of three distinct reactor models considering factors, such as boundary conditions, material properties, and thermal-mechanical loading. In this study, Beryllium Oxide (BeO), Beryllium (Be), Aluminum Oxide (Al2O3), and Magnesium Oxide (MgO) are chosen as materials for the reflector. Yttrium Hydride (YH) and Zirconium Hydride (ZH) are chosen as moderators. Uranium Nitride (UN) and Uranium Molybdenum (UMo) are chosen as reactor fuel materials. The thermal analysis predicts the deformation due to the thermal expansion within the reactor under steady operating conditions at 25 kWth, mimicking the maximum rated power of the Zebra kW design. The mechanical study simulates the system's response to forced vibration loads applied along the cooling channels, matching the natural frequency of the system. The results from both analyses show that Beryllium Oxide, Yttrium Hydride, and Uranium Nitride demonstrate the most optimal stress distribution in the system compared to other configurations investigated here. The results of this study can be developed into datasets to facilitate future machine learning studies, enabling the prediction of mechanical and thermal responses for micro-reactors.

Severe Electron Environment for Surface Charging at Geostationary and Medium Earth Orbits

Electron radiation environment with keV energies on medium earth orbit (MEO) is investigated around the times when worst-case severe environments for surface charging were detected at Los Alamos National Laboratory (LANL) satellites on geostationary earth orbit (GEO). The Inner Magnetosphere Particle Transport and Acceleration Model (IMPTAM) is employed to model 1–100 keV electron fluxes in the inner Earth’s magnetosphere (inside 10RE) during four representative events selected out of 400 LANL worst-case severe environment events. Modeled fluxes are compared to the observed ones on GEO, and the peak electron fluxes are then extracted at L=4.6 which is considered as approximate MEO environment following the LANL events. IMPTAM generally reproduces the 10–50 keV electron fluxes on GEO but underestimates (of factor of 2 to 5) at energies above. It is found that the maximum electron flux on MEO is reached in about 1.5–2 h after the worst-case environment for surface charging was detected at GEO. Whereas the magnetic local time (MLT) location of the worst-case severe environments on GEO varies from 23 to 05, the maximum electron flux on MEO is located on 6–7.8 MLT. The maximum electron flux values on MEO can be 2 to 10 times higher than those observed on GEO and those estimated using European Cooperation for Space Standardization and National Aeronautics and Space Administration guidelines, which can be a significant increase of the risks in terms of surface charging.

Key Factors for Electrochemical Carbon Dioxide Reduction at Ni-N-C Catalysts

Electrochemical carbon dioxide reduction reaction (CO2RR) has the potential to adequately contribute to addressing the energy and environmental challenges faced by the humanity today. The surplus of CO2 produced by burning fossil fuels can be transformed into valuable products by CO2RR. An effective use of this approach on a large scale requires active, selective, and stable CO2 reduction electrocatalysts. Additionally, insightful understanding of interfacial behavior such as water wetting and carbonate formation at the electrode is required to enhance the performance and durability of CO2RR electrocatalysts.1 Atomically dispersed Ni-N-C materials have attracted attention due to their superior selectivity for CO generation.2 Their activity and selectivity of CO2RR are influenced by the metal center and local atomic defects in M-N-C catalysts.3 In addition to catalyst structures, electrode composition and structure have also substantial impact on the activity and selectivity of CO2RR. Particularly, ionomer compositions and the electrode fabrication process can alter the hydrophobicity of the electrode and the local pH on the catalyst, resulting in considerable changes in CO2RR activity and selectivity.In this presentation, we will report on the performance of various electrodes fabricated with the Ni-N-C catalyst, using different types of ionomers and measured in a flow cell and zero-gap electrolyzer at > 100 mA/cm2 current densities for CO2RR. We will also introduce an approach that aims at reducing carbonate formation at the CO2RR electrolyzer cathode by the modifications to the electrolyte composition, the CO2 inlet humidity, and the electrochemical cell temperature. Acknowledgement Research presented in this work was supported by the Laboratory Directed Research and Development program of Los Alamos National Laboratory under project number 20230065DR. References (1) Sa, Y. J.; Lee, C. W.; Lee, S. Y.; Na, J.; Lee, U.; Hwang, Y. J. Catalyst–electrolyte interface chemistry for electrochemical CO2 reduction. Chemical Society Reviews 2020, 49 (18), 6632-6665.(2) Wu, J.; Sharifi, T.; Gao, Y.; Zhang, T.; Ajayan, P. M. Emerging Carbon-Based Heterogeneous Catalysts for Electrochemical Reduction of Carbon Dioxide into Value-Added Chemicals. Advanced Materials 2019, 31 (13), 1804257.(3) Liang, S.; Huang, L.; Gao, Y.; Wang, Q.; Liu, B. Electrochemical Reduction of CO2 to CO over Transition Metal/N-Doped Carbon Catalysts: The Active Sites and Reaction Mechanism. Advanced Science 2021, 8 (24), 2102886.

Mixed Potential Sensors for the Detection of Hydrogen Leaks from Geologic Reservoirs

Large-scale hydrogen (H2) geologic storage presents a viable alternative to surface storage that is both safer and more economical. One option being considered by DOE is H2 storage in salt formations. These formations have been successfully used for gas storage for decades due to their extremely low permeability and may see significant investment as the US ramps up its R&D efforts in this field. New Mexico has a unique advantage in that bedded salt formations are located strategically in areas where excess energy production can be harnessed for hydrogen production. However, bedded salt is more permeable than domal salt, necessitating sensor deployment to monitor H2 containment. Robust sensors that can provide early leakage detection will be an essential component of the safety of H2 operating facilities. In a LANL-funded Mission Foundations Research (MFR) project, we prepared several zirconia-based mixed potential hydrogen sensors utilizing a tin-doped indium oxide electrode for H2 leak detection to test its stability in subsurface environments. Previous electrochemical sensor work has shown this type of sensor in a hydrogen safety sensor role represents a significant improvement over currently available sensors as it has an extremely stable baseline and limited cross sensitivity to other gaseous compounds.1 The feasibility of this technology will be demonstrated through a hydrogen permeation experiment to measure rates of underground hydrogen permeation between boreholes drilled underground at the DOE Waste Isolation Pilot Plant (WIPP) site. This experiment will (1) establish the use of this novel sensor in geologic H2 storage applications and (2) investigate the feasibility of H2 storage in bedded rock salt. Acknowledgement This research is supported by the Los Alamos National Laboratory, Laboratory Directed Research and Development (LDRD) Office, Missions Foundation Research Charter (Debora Wagner Program Manager). References E. L. Brosha, C. J. Romero, D. Poppe, T. L. Williamson, C. R. Kreller, R. Mukundan, R. S. Glass, and A. S. Wu, “Field Trials Testing of Mixed Potential Electrochemical Hydrogen Safety Sensors at Commercial California Hydrogen Filling Stations,” Journal of the Electrochemical Society 164 (13) B681-B689 (2017).

An Increase in the Prevalence of Clinically Relevant Resistance-Associated Substitutions in Four Direct-Acting Antiviral Regimens: A Study Using GenBank HCV Sequences.

Direct-acting antivirals (DAAs) revolutionized the therapeutics of chronic hepatitis C. The emergence and transmission of HCV variants with resistance-associated substitutions (RASs) can undermine HCV treatment. This study aimed to assess the prevalence and temporal trends of RASs in HCV, with a particular focus on clinically relevant RASs (cr-RASs). Near-complete HCV GenBank sequences archived in the Los Alamos HCV Database were analyzed. The study period was divided into two phases: before 2011 and from 2011 onward. Identification of RASs across three DAA classes (NS3, NS5A, and NS5B inhibitors) was based on the 2020 EASL guidelines. The AASLD-IDSA recommendations were used to identify cr-RASs for three HCV genotypes/subtypes (1a, 1b, and 3) and four DAA regimens: ledipasvir/sofosbuvir; elbasvir/grazoprevir; sofosbuvir/velpatasvir; and glecaprevir/pibrentasvir. The final HCV dataset comprised 3443 sequences, and the prevalence of RASs was 50.4%, 60.2%, and 25.3% in NS3, NS5A, and NS5B, respectively. In subtype 1a, resistance to ledipasvir/sofosbuvir was 32.8%, while resistance to elbasvir/grazoprevir was 33.0%. For genotype 3, resistance to sofosbuvir/velpatasvir and glecaprevir/pibrentasvir was 4.2% and 24.9%, respectively. A significant increase in cr-RASs was observed across the two study phases as follows: for ledipasvir/sofosbuvir in subtype 1a, cr-RASs increased from 30.2% to 35.8% (p = 0.019); for elbasvir/grazoprevir in subtype 1a, cr-RASs increased from 30.4% to 36.1% (p = 0.018); In subtype 1b, neither ledipasvir/sofosbuvir nor elbasvir/grazoprevir showed any cr-RASs in the first phase, but both were present at a prevalence of 6.5% in the second phase (p < 0.001); for sofosbuvir/velpatasvir in genotype 3, cr-RASs increased from 0.9% to 5.2% (p = 0.006); and for glecaprevir/pibrentasvir, cr-RASs increased from 12.0% to 29.1% (p < 0.001). The rising prevalence of HCV RASs and cr-RASs was discernible. This highlights the necessity for ongoing surveillance and adaptation of novel therapeutics to manage HCV resistance effectively. Updating the clinical guidelines and treatment regimens is recommended to counteract the evolving HCV resistance to DAAs.

(Invited) Unlocking Long-Duration Energy Storage with Unitized Reversible Fuel Cells

As the proportion of energy supplied by renewable sources continually rises, the intermittent nature of these sources necessitates efficient energy storage to meet the demand of the grid. Hydrogen is a promising energy carrier for grid-scale storage due to its capacity for months-long storage without energy loss or self-discharge.(1) Reversible fuel cells generate power for the grid in fuel cell (FC) mode during periods when renewable power production is lower than demand, utilizing stored H2 generated by water electrolysis (WE) during periods when renewable power production exceeds demand from the grid. Unitized reversible fuel cells (URFCs) efficiently integrate WE and FC operation in a single electrochemical device, potentially reducing costs and providing higher energy density. In constant gas URFC operational configuration, both the oxygen evolution reaction (OER) for WE and the oxygen reduction reaction (ORR) for FC occur within the same electrode.(2) The contrasting electrode requirements for FC and WE have constrained the round-trip efficiency (RTE) of URFCs, highlighting the crucial need to improve RTE for greater competitiveness and widespread commercial adoption. This presentation will discuss the results from development of novel bifunctional catalysts, electrode architectures, and porous transport layers (PTLs) aimed at enhancing efficiency and durability of URFCs. This talk will present the development of bifunctional catalysts and their supports to boost OER and ORR performance. Additionally, we will present insights into innovative electrode architecture designed for optimal utilization of the catalysts, thereby maximizing efficiency. The development of specialized PTLs featuring amphiphilic wettability and intricately engineered microporous layers will be presented emphasizing their role in increasing the performance and durability of URFCs. Acknowledgement This research is supported by the Laboratory Directed Research and Development (LDRD) program at Los Alamos National Laboratory (LANL) under project 20240061DR, and by the U.S. Department of Energy Hydrogen and Fuel Cell Technologies Office (DOE-HFTO) with support from technology manager Donna Ho. References Hydrogen Council, Hydrogen scaling up: a sustainable pathway for the global energy transition, in (2017).S. Komini Babu et al., Advanced Energy Materials, 13, 2203952 (2023).

Characterization of SimulCam, a standoff Raman system for scientific support of SuperCam operations on Mars

During the development activities of SuperCam Calibration Target, target intended for one of the two first Raman instruments to be deployed on another planetary body, our group developed a laboratory instrument that could simulate to some extent the Raman capabilities of one of such instruments and could provide data with similar quality. The use of this kind of laboratory instruments has demonstrated its utility in the evaluation of potential calibration targets or anticipating the science outcome that an instrument could provide. The present work describes our laboratory setup to support SuperCam, evaluating similarities between both instruments, despite of differences in the hardware. Evaluation of data gathered by SuperCam on Mars and the availability of one replica of SuperCam’s Calibration Target allowed the comparison on the same set of targets, demonstrating how similar Signal-to-Noise Ratio (SNR) could be achieved from both instruments. The higher energy per pulse on SimulCam is compensated by a greater analytical footprint and the use of smaller collection optics. The results show how spectra obtained at representative distances of SuperCam are comparable. Operational principles are also comparable in terms of time resolution, and close in terms of spectral resolution.This similarity has allowed different science support works using SimulCam data, as well as the support to Mars detections using our setup. We provide examples of this support that will be shared with the community in different papers, as well as examples of possible operations activities that could benefit from experiments performed with SimulCam. We show how this setup can complement the two laboratory replicas in Los Alamos and Toulouse in providing support data to different experiments.

Gallium oxide (Ga2O3) energy dependent scintillation response to fast neutrons and flash gamma-rays.

Gallium oxide is a newly emerged ultrawide bandgap (4.9eV) semiconductor that is suitable as a combined electronics and radiation detection platform. We have experimentally demonstrated fast neutron and gamma-ray scintillation from Czochralski-grown β-Ga2O3 in a recent series (October 2023) of experiments at the unmoderated pulsed neutron spallation source located at the Los Alamos Neutron Science Center. Using the neutron time-of-flight (TOF) technique and a fast-gated intensified CCD camera, we observed energy-dependent neutron scintillation for neutron energies ranging from 1 to 400MeV, including the 14.1MeV neutron energy relevant to D-T fusion. Neutron flux is quantified and calibrated by cascading the scintillator after the fission chamber, enabling a detailed analysis of temporal and energy-dependent characteristics of the scintillation events. A pronounced scintillation signal from the spallation gamma flash with a temporal full width of half maximum of ∼4ns is indicative of the material's rapid response. Neutron energy dependent scintillation is observed using the TOF method at a 22.6-m distance from the neutron source. These results highlight the possibility of developing a Ga2O3 based fusion neutron diagnostic platform integrated with both scintillation and electronics functions on the integrated chip scale.

Large-grain scintillator screens for proton radiography.

Protons from the Los Alamos Neutron Science Center have been used for pulsed radiography in dynamic experiments for the past 25 years. Pulses of protons are imaged on a scintillator, and the light from these images is captured by fast gated cameras. The need for fast, bright scintillators has led to some compromises in image quality due to tiling the scintillators and backgrounds with totally internally reflected light. We show how large-grain scintillator screens, made using a thin plastic binder, solve these problems.

Exploring disparities in HIV-1 pretreatment and acquired drug resistance in China from 2003 to 2022.

To investigate the epidemic patterns of pretreatment drug resistance (PDR) and acquired drug resistance (ADR) in HIV-1 sequences from China. HIV-1 pol sequences and associated epidemiological data were collected from the Los Alamos HIV Sequence Database, NCBI, HIV Gene Sequence Database and PubMed. Genotypic resistance and subtypes were identified using the Stanford HIV Drug Resistance Database. A total of 36 263 sequences from ART-naïve individuals and 1548 sequences from ART-experienced individuals with virological failure were evaluated. PDR prevalence was 6.64%, initially decreasing and then increasing to 7.84% (2018-22) due to NNRTI. Pooled ADR prevalence (44.96%) increased, with NNRTI and NRTI aligning with the overall trend. The percentage of multidrug resistance was more than that of single-drug resistance in PDR and especially ADR annually. PDR was most prevalent in Central China followed by Southwest and North. ADR prevalence was highest in North China followed by Northwest and Southwest. In ADR sequences, high-level resistance was more common, especially in NRTI. PDR sequences exhibited low-level or intermediate resistance, especially PI. Drug resistance mutations revealed distinct patterns in PDR and ADR. CRF01_AE, the predominant subtype in China, exhibited the highest proportions among most ART drugs and drug resistance mutations, with a few exceptions where CRF07_BC (prominent in the Northwest), CRF55_01B and CRF08_BC (prominent in the Southwest) showed the highest proportions. HIV-1 PDR and ADR prevalence in China exhibited diverse epidemiological characteristics, underscoring the importance of ongoing national monitoring of PDR, ADR and subtype; patient education on adherence; and personalized regimens.

Development and Optimization of Oligonucleotide Ligation Assay (OLA) Probes for Detection of HIV-1 Resistance to Dolutegravir.

The WHO currently recommends dolutegravir (DTG)-based ART for persons living with HIV infection in resource-limited-settings (RLS). To expand access to testing for HIV drug resistance (DR) to DTG in RLS, we developed probes for use in the oligonucleotide ligation assay (OLA)-Simple, a near-point of care HIV DR kit. Genotypic data from clinical trials and case reports were used to determine the mutations in HIV-1 integrase critical to identifying individuals with DTG-resistance at virologic failure of DTG-based ART. Probes to detect G118R, Q148H/K/R, N155H and R263K in HIV-1 subtypes A, B, C, D and CRF01_AE were designed using sequence alignments from the Los Alamos database and validated using 61 clinical samples of HIV-1 subtypes A, B, C, D, CRF01_AE genotyped by PacBio (n = 15) or Sanger (n = 46). Initial OLA probes failed to ligate for 16/244 (6.5%) codons (9 at G118R and 7 at Q148H/K/R). Probes revised to accommodate polymorphisms interfering with ligation at codons G118R and Q148R reduced indeterminates to 3.7% (5 at G118R and 4 at Q148H/K/R) and detected DTG-mutations with a sensitivity of 96.5% and 100% specificity. These OLA DTG resistance probes appear highly sensitive and specific across HIV-1 subtypes common in RLS with high burden of HIV infection.