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At least 451 records · Page 25

A newly characterized malaria antigen on erythrocyte and merozoite surfaces induces parasite inhibitory antibodies

We previously identified a Plasmodium falciparum (Pf) protein of unknown function encoded by a single-copy gene, PF3D7_1134300, as a target of antibodies in plasma of Tanzanian children in a whole-proteome differential screen. Here we characterize this protein as a blood-stage antigen that localizes to the surface membranes of both parasitized erythrocytes and merozoites, hence its designation as Pf erythrocyte membrane and merozoite antigen 1 (PfEMMA1). Mouse anti-PfEMMA1 antisera and affinity-purified human anti-PfEMMA1 antibodies inhibited growth of P. falciparum strains by up to 68% in growth inhibition assays. Following challenge with uniformly fatal Plasmodium berghei (Pb) ANKA, up to 40% of mice immunized with recombinant PbEMMA1 self-cured, and median survival of lethally infected mice was up to 2.6-fold longer than controls (21 vs. 8 d, P = 0.005). Furthermore, high levels of naturally acquired human anti-PfEMMA1 antibodies were associated with a 46% decrease in parasitemia over 2.5 yr of follow-up of Tanzanian children. Together, these findings suggest that antibodies to PfEMMA1 mediate protection against malaria.

60 APPLIED LIFE SCIENCES↗

Non-solvents as physical blowing agents in printable silicone foams

Silicone foams were produced by dispersing an incompatible liquid phase (i.e. a non-solvent) into an uncured, liquid silicone. The formulation and processing parameters were varied to see the effect on porosity and pore morphology. Specifically, two fluorosilanes were added to stabilize the inclusion of fluorinated solvents as blowing agents. As the floruosilane content increased, the void content increased up to about 44 vol. % when the fluorosilane comprised 18 wt. % of the initial formulation. Fumed silica that was treated with a fluorinated silane was also used to try to stabilize the dispersed liquid. While the fumed silica content did not have a strong effect on the total void content, the morphology changed when silica content changed. Various fluorinated solvents with distinct chemical structures were used as the non-solvent and then removed after curing of the silicone. The interaction of the internal non-solvent phase and the silicone phase was expected to influence the porosity. These insights highlight how the manipulation of formulation and processing parameters, focusing on the inclusion of fluorosilanes and fluorinated solvents, contributes to the understanding of how incompatible liquid phases interact with silicone matrices to control porosity and pore morphology. Additionally, these interactions also influenced processability, leading to formulations that could be printed. Higher content of non-solvent inclusions could increase the yield stress and storage modulus of an uncured formulation, leading to the ability to tune intrastrand porosity while a 3D printed architecture could be modified to introduce porosity between the strands. Furthermore, in addition to fluorinated solvents, we also considered non-fluorinated solvents since these may be more industrially relevant in the future. Overall, this approach provides an alternative route to producing porous foams that can be 3D printed, which could be useful for applications like cushioning and protective gear.

physical blowing agent↗

Renormalized site density functional theory

Site density functional theory (SDFT) provides a rigorous framework for statistical mechanics analysis of inhomogeneous molecular liquids. The key defining feature of these systems is the presence of two very distinct interactions scales (intra- and inter-molecular), and as such proper description of both effects is critical to the accuracy of the calculations. Current SDFT applications utilize the same approximation scheme for both interaction motifs, which negatively impacts the results. Dual space methodology, used in this work, alleviates this issue by providing the flexibility of evaluating part of the interactions in traditional field representation. For molecular liquid this translates into retaining density representation for inter-molecular interactions but describing stiff intra-molecular remainder by more appropriate conventional field based methods. This opens the way to decouple analysis of the two interactions scales - the idea which is developed further in this work for the case of homogeneous reference approximation of inter-molecular interactions. We demonstrate that by defining new collective variables, the behavior of the original molecular liquid system at the inter-molecular level can be transformed to resemble that of an effective simple fluid mixture. The latter is linked to intra-molecular scale through renormalized interaction parameters. We illustrate this renormalization procedure for several types of diatomic liquids, showing that this approach cures many of the shortcomings of existing SDFT methods.

Chuev, Gennady N.↗

Metabolic Response in Patients With Post-treatment Lyme Disease Symptoms/Syndrome

Abstract Background Post-treatment Lyme disease symptoms/syndrome (PTLDS) occurs in approximately 10% of patients with Lyme disease following antibiotic treatment. Biomarkers or specific clinical symptoms to identify patients with PTLDS do not currently exist and the PTLDS classification is based on the report of persistent, subjective symptoms for ≥6 months following antibiotic treatment for Lyme disease. Methods Untargeted liquid chromatography–mass spectrometry metabolomics was used to determine longitudinal metabolic responses and biosignatures in PTLDS and clinically cured non-PTLDS Lyme patients. Evaluation of biosignatures included (1) defining altered classes of metabolites, (2) elastic net regularization to define metabolites that most strongly defined PTLDS and non-PTLDS patients at different time points, (3) changes in the longitudinal abundance of metabolites, and (4) linear discriminant analysis to evaluate robustness in a second patient cohort. Results This study determined that observable metabolic differences exist between PTLDS and non-PTLDS patients at multiple time points. The metabolites with differential abundance included those from glycerophospholipid, bile acid, and acylcarnitine metabolism. Distinct longitudinal patterns of metabolite abundance indicated a greater metabolic variability in PTLDS versus non-PTLDS patients. Small numbers of metabolites (6 to 40) could be used to define PTLDS versus non-PTLDS patients at defined time points, and the findings were validated in a second cohort of PTLDS and non-PTLDS patients. Conclusions These data provide evidence that an objective metabolite-based measurement can distinguish patients with PTLDS and help understand the underlying biochemistry of PTLDS.

Immunology↗

Immunological Correlates of the HIV-1 Replication-Competent Reservoir Size

Understanding what shapes the latent human immunodeficiency virus type 1 (HIV-1) reservoir is critical for developing strategies for cure. Here, we measured frequency of persistent HIV-1 infection after 5 years of suppressive antiretroviral therapy initiated during chronic infection. Pretreatment CD8 + T-cell activation, nadir CD4 count, and CD4:CD8 ratio predicted reservoir size.

60 APPLIED LIFE SCIENCES↗

Identification of 2 Novel Subtypes of Hepatitis C Virus Genotype 8 and a Potential New Genotype Successfully Treated With Direct Acting Antivirals

Abstract Background Hepatitis C virus (HCV) has high genetic diversity and is classified into 8 genotypes and >90 subtypes, with some endemic to specific world regions. This could compromise direct-acting antiviral efficacy and global HCV elimination. Methods We characterized HCV subtypes “rare” in the United Kingdom (non-1a/1b/2b/3a/4d) by means of whole-genome sequencing via a national surveillance program. Genetic analyses to determine the genotype of samples with unresolved genotypes were undertaken by comparison with International Committee on Taxonomy of Viruses HCV reference sequences. Results Two HCV variants were characterized as being closely related to the recently identified genotype (GT) 8, with >85% pairwise genetic distance similarity to GT8 sequences and within the typical intersubtype genetic distance range. The individuals infected by the variants were UK residents originally from Pakistan and India. In contrast, a third variant was only confidently identified to be more similar to GT6 compared with other genotypes across 6% of the genome and was isolated from a UK resident originally from Guyana. All 3 were cured with pangenotypic direct-acting antivirals (sofosbuvir-velpatasvir or glecaprevir-pibrentasvir) despite the presence of resistance polymorphisms in NS3 (80K/168E), NS5A (28V/30S/62L/92S/93S) and NS5B (159F). Conclusions This study expands our knowledge of HCV diversity by identifying 2 new GT8 subtypes and potentially a new genotype.

59 BASIC BIOLOGICAL SCIENCES↗

A Novel Signaling Pathway Connects Thiamine Biosynthesis, Bacterial Respiration, and Production of the Exopolysaccharide Amylovoran in Erwinia amylovora

Erwinia amylovora is a plant pathogen causing necrotrophic fire blight disease of apple, pear, and other rosaceous plants. This bacterium colonizes host vascular tissues via the production of exopolysaccharides (EPSs) including amylovoran. It is well-established that the nearly ubiquitous plasmid pEA29 of E. amylovora is an essential virulence factor, but the underlying mechanism remains uncharacterized. Here, we demonstrated that pEA29 was required for E. amylovora to produce amylovoran and to form a biofilm, and this regulation was dependent on the thiamine biosynthesis operon thiOSGF. We then conducted carbohydrate and genetic analyses demonstrating that the thiamine-mediated effect on amylovoran production was indirect, as cells lacking thiOSGF produced an EPS that did not contain glucuronic acid, one of the key components of amylovoran, whereas the transcriptional activity and RNA levels of the amylovoran biosynthesis genes were not altered. Alternatively, addition of exogenous thiamine restored amylovoran production in the pEA29-cured strain of E. amylovora and positively impacted amylovoran production in a dose-dependent manner. Individual deletion of several chromosomal thiamine biosynthesis genes also affected amylovoran production, implying that a complete thiamine biosynthesis pathway is required for the thiamine-mediated effect on amylovoran production in E. amylovora. Finally, we determined that an imbalanced tricarboxylic acid cycle negatively affected amylovoran production, which was restored by addition of exogenous thiamine or overexpression of the thiOSGF operon. In summary, our report revealed a novel signaling pathway that impacts E. amylovora virulence in which thiamine biosynthesis enhances bacterial respiration that provides energetic requirements for the biosynthesis of EPS amylovoran.

59 BASIC BIOLOGICAL SCIENCES↗

Forward sensitivity approach for estimating eddy viscosity closures in nonlinear model reduction

In this paper, we propose a variational approach to estimate eddy viscosity using forward sensitivity method (FSM) for closure modeling in nonlinear reduced order models. FSM is a data assimilation technique that blends model's predictions with noisy observations to correct initial state and/or model parameters. We apply this approach on a projection based reduced order model (ROM) of the one-dimensional viscous Burgers equation with a square wave defining a moving shock, and the two-dimensional vorticity transport equation formulating a decay of Kraichnan turbulence. We investigate the capability of the approach to approximate an optimal value for eddy viscosity with different measurement configurations. Specifically, we show that our approach can sufficiently assimilate information either through full field or sparse noisy measurements to estimate eddy viscosity closure to cure standard Galerkin reduced order model (GROM) predictions. Therefore, our approach provides a modular framework to correct forecasting error from a sparse observational network on a latent space. We highlight that the proposed GROM-FSM framework is promising for emerging digital twin applications, where real-time sensor measurements can be used to update and optimize surrogate model's parameters.

42 ENGINEERING↗

Shifting Left for Machine Learning: An Empirical Study of Security Weaknesses in Supervised Learning-based Projects

Context: Supervised learning-based projects (SLPs), i.e., software projects that use supervised learning algorithms, such as decision trees are useful for performing classification-related tasks. Yet, security weaknesses, such as the use of hard-coded passwords in SLPs, can make SLPs susceptible to security attacks. A characterization of security weaknesses in SLPs can help practitioners understand the security weaknesses that are frequent in SLPs and adopt adequate mitigation strategies. Objective: The goal of this paper is to help practitioners se-curely develop supervised learning-based projects by conducting an empirical study of security weaknesses in supervised learning-based projects. Methodology: We conduct an empirical study by quantifying the frequency of security weaknesses in 278 open source SLPs. Results: We identify 22 types of security weaknesses that occur in SLPs. We observe ‘use of potentially dangerous function’ to be the most frequently occurring security weakness in SLPs. Of the identified 3,964 security weaknesses, 23.79 % and 40.49 % respectively, appear for source code files used to train and test models. We also observe evidence of co-location, e.g., instances of command injection co-locates with instances of potentially dangerous function. Conclusion: Based on our findings, we advocate for a shift left approach for SLP development with security-focused code reviews, and application of security static analysis.

Bhuiyan, Farzana Ahamed↗

Encapsulation Residual Stress and Ferrite Loss in Inductive Coil Assemblies

As inductive wireless charging reaches higher power levels, thermal management and mechanical durability become more critical. To address these concerns, past works have demonstrated the benefit of encapsulating coil assemblies in thermally conductive materials. However, due to the sensitivity of the MnZn ferrites commonly used in coil assemblies to mechanical stress, care must be taken to avoid creating large stresses in the ferrite that cause higher hysteresis loss. The stress formation in the encapsulant curing process is overviewed and modeled and an experiment is performed to demonstrate the effect in a small-scale coil assembly. Finally, the effect is shown in the reduced coil-coil efficiency of a first generation high power inductive power transfer prototype using a stiff epoxy compared to better performance in a second prototype using a softer thermally-conductive silicone encapsulant.

Foote, Andrew↗

Investigating the Crosslinking, Degradation, and Adhesion Behavior of Photovoltaic Encapsulants Under Thermal Accelerated Aging

Degradation of photovoltaic (PV) module encapsulant characteristics that lead to mechanical embrittlement and delamination remains a cause of failure in solar installations. A multiscale reliability model connecting the encapsulant mechanical and fracture properties to the degraded molecular structure and interfacial bonding to adjacent solar cell and glass substrates was previously published. The model, developed primarily for poly(ethylene-co-vinyl acetate) acetate (EVA) encapsulants, remains to be experimentally validated. Determining the degradation and crosslinking kinetics of alternative encapsulants, such as polyolefin elastomer (POE) and EVA/POE/EVA composites (EPE), can generalize the model. In this work, we subject fully cured EVA, POE, and EPE encapsulants to accelerated thermal aging to determine how high temperatures impact reaction kinetics. An increase in gel content (crosslinking) and decrease in crystallinity of the encapsulants under hot-aerobic (90 degrees C, 22% RH) and hot-anaerobic (90 degrees C, sealed in N 2 air) aging were observed, even in the absence of UV and crosslinking initiators. Fourier transform infrared spectroscopy (FTIR)-attenuated total reflectance analysis showed insignificant encapsulant degradation, demonstrating the critical role of UV and moisture in accelerating degradation. Adhesion testing performed on coupon-level specimens (cell/encapsulant/glass laminates) showed decreases in adhesion energy, Gc , from 5000 h of hot-dry (90 degrees C, ~1% RH) and hot-humid (90 degrees C, 60% RH) aging. POE coupons demonstrated the best stability, followed by EPE then EVA. For EVA and POE, hot-humid aged coupons experienced a larger decrease in Gc due to enhanced hydrolytic degradation. Hot-dry aging condition demonstrated that thermal degradation of the interface could be significant even if the encapsulant experiences negligible degradation in the absence of UV and elevated humidity.

accelerated aging↗

Design of a High Toughness Epoxy for Superconducting Magnets and Its Key Properties

Nb 3 Sn accelerator magnets are poised to enable the luminosity upgrade of the Large Hadron Collider (LHC) at CERN, improving its potential for exploring physics beyond the standard model of particle physics. The prototype Nb 3 Sn magnets consistently need 10–25 quenches to achieve their best performance. A hypothesis is that the long training of these magnets may at least be partially induced by epoxy cracking and bonding failures. In 2018, we showed that several existing epoxies have a higher toughness and less tendency to crack at low temperatures than CTD-101K, the epoxy resin with which almost all Nb 3 Sn accelerator magnets have been impregnated. Here we explore a new high toughness formulation for reducing quench training of Nb 3 Sn accelerator magnets, through combining two amine curing agents to achieve a good glass transition temperature (T g ), adding a viscosity reducer to achieve low viscosity, and experimenting a coupling agent for improved bonding strengths. In this work, we report results of comprehensive materials tests, including thermal shock, tensile, compressive, shear tests, viscosity and T g tests.

75 CONDENSED MATTER PHYSICS, SUPERCONDUCTIVITY AND↗

Mechanical Design of the Interaction Region Dipole B1pF for Electron Ion Collider

Here, the Electron-Ion Collider (EIC), planned for construction at Brookhaven National Laboratory, will consist of two intersecting beams of intense electrons and high-energy protons or heavier atomic nuclei. The collider will need many demanding components, including high field superconducting magnets for the Interaction Region (IR). It has been decided that a prototype of one such magnet, the B1pF dipole, shall be built, to validate design choices common to all Rutherford cable dipole and quadrupole IR magnets. B1pF is one of several high field magnets in the interaction region whose design is based on the 15.1 mm wide NbTi cable, a cable like the one used in the main dipole coil of the Large Hadron Collider (LHC) at CERN. The current design is based on a single layer coil with an inner diameter of 300 mm and magnetic length of ~3 m which generates a magnetic field at the center of the magnet of about 3.7 T at a current of ~11 kA at design. This paper presents the mechanical design of the B1pF dipole magnet, and the R&D effort associated with the development of the prototype, including tests for successfully winding and curing coils of the needed configuration into proper structural and magnetic elements, and including a multilayer magnetic return yoke which meets field requirements while providing an initial reduced structure suitable for operational testing in an existing test facility.

75 CONDENSED MATTER PHYSICS, SUPERCONDUCTIVITY AND↗

Design and Construction of a Prototype B1pF Large Aperture Rutherford Cable Superconducting Magnet for the EIC Interaction Region

Brookhaven National Laboratory (BNL) was chosen to host the international Electron-Ion Collider (EIC), which will collide high energy and highly polarized hadron and electron beams with a center of mass energy up to 140 GeV. The Interaction Region (IR) requires several large aperture, relatively high field superconducting dipole and quadrupole magnets, some of which are very closely spaced. B1pF is a large aperture (300 mm coil ID), medium field (4.2 T), 3 meter long superconducting dipole magnet. Its size is larger than the largest superconducting magnet in the RHIC accelerator (180 mm DX dipole, 4.2 T, 3.7 m long). As such, B1pF was chosen as the representative magnet to be prototyped to demonstrate the technological choice, design and construction details. Here, this paper describes the analyses and considerations which informed both the magnet and magnet tooling designs. This paper will summarize the construction results so far, in particular the plan for novel coil winding tooling and the test coil winding & curing program that was carried out prior to coil and magnet construction.

75 CONDENSED MATTER PHYSICS, SUPERCONDUCTIVITY AND↗

Niacin for Parkinson's disease

Abstract Parkinson's disease (PD) is a neurodegenerative disease associated with progressive loss of motor function and cognitive decline occurring in 1% of the USA population. There is no cure for PD, and current treatment regimens are directed towards treating symptoms and not treating the underlying cause of the disease. Chronic neuroinflammation is associated with loss of neuronal cells, leading to motor and cognitive decline. Current clinical trials on drugs and nutraceuticals, such as coenzyme Q10 and niacin, are being carried out to delay progression and reduce damage by inflammatory molecules, such as reactive oxygen species and cytokines, in PD patients. In this review, we present available clinical trials and the role of niacin in reducing neuroinflammation in PD.

Seamon, Marissa↗

Economic evaluation of the Hepatitis C virus elimination program in the country of Georgia, 2015 to 2017

Abstract Background and Aims In 2015, the country of Georgia launched an elimination program aiming to reduce the prevalence of Hepatitis C virus (HCV) infection by 90% from 5.4% prevalence (~150 000 people). During the first 2.5 years of the program, 770 832 people were screened, 48 575 were diagnosed with active HCV infection, and 41 483 patients were treated with direct‐acting antiviral (DAA)‐based regimens, with a >95% cure rate. Methods We modelled the incremental cost‐effectiveness ratio (ICER) of HCV screening, diagnosis and treatment between April 2015 and November 2017 compared to no treatment, in terms of cost per quality‐adjusted life year (QALY) gained in 2017 US dollars, with a 3% discount rate over 25 years. We compared the ICER to willingness‐to‐pay (WTP) thresholds of US$4357 (GDP) and US$871 (opportunity cost) per QALY gained. Results The average cost of screening, HCV viremia testing, and treatment per patient treated was $386 to the provider, $225 to the patient and $1042 for generic DAAs. At 3% discount, 0.57 QALYs were gained per patient treated. The ICER from the perspective of the provider including generic DAAs was $2285 per QALY gained, which is cost‐effective at the $4357 WTP threshold, while if patient costs are included, it is just above the threshold at $4398/QALY. All other scenarios examined in sensitivity analyses remain cost‐effective except for assuming a shorter time horizon to the end of 2025 or including the list price DAA cost. Reducing or excluding DAA costs reduced the ICER below the opportunity‐cost WTP threshold. Conclusions The Georgian HCV elimination program provides valuable evidence that national programs for scaling up HCV screening and treatment for achieving HCV elimination can be cost‐effective.

Tskhomelidze, Irina↗

Thermal Analysis of Large Area Additive Manufacturing Resistance Heating Composites for Out of Oven/Autoclave Applications

Additive Manufacturing (AM) of carbon fiber (CF) reinforced composite has received growing attention because of the design flexibility, superior mechanical properties, improved thermal properties, and weight reduction. Autoclave tooling was proven to be a successful application for large scale AM technology. The capital cost, and cost associated with heating, and cycle time in a conventional autoclave process is relatively high. Thus, an innovative design of AM mold with an efficient heating scheme is essential. This study represents an innovative method of the resistive heating of composite molds which does not require a room size oven for heating during the curing processing. Therefore, it has the potential to reduce the operating cost drastically. For the design validation and feasibility study, we performed a numerical analysis of the wire embedded and AM mold parts. The goal of this study is to determine and optimize the thermal behavior of the printed mold with embedded wire technology. It is anticipated that the larger distance between the embedded wires along the printing direction (z-direction) increase the cold spot, on the other hand, a close distance of the wire can create the unwanted localize heating, thus melting. Constant thermal properties of the 20 wt.% short CF reinforced acrylonitrile butadiene styrene (ABS) was used for the simulation purpose. Thermal characterization was set to 100°C to avoid the thermal deformation or bulging on the part surface.

billah, Kazi↗

Infrared thermography NDT for in-situ defect detection in sandwich composite panel manufacturing

Composite manufacturing presents numerous challenges, as defects can arise from various sources throughout the process. In sandwich composite structures, the integration of a foam core introduces additional complexity and increases the likelihood of defect formation like delamination. To mitigate these issues and reduce the risk of future structural failures, in-situ monitoring during manufacturing is essential. This study investigates infrared (IR) thermography as a non-destructive technique for detecting manufacturing defects in foam-core sandwich composite panels under thermally excited conditions representative of in-situ processing. A stationary FLIR A8590 IR camera (640 × 512 pixels, 30Hz, 17mm lens, 9 ft stand-off distance) was used to monitor prefabricated panels subjected to controlled external heating simulating compression molding and resin cure exotherm. Interlaminar delamination defects with characteristic sizes ranging from 0.25 × 0.25in² to 5 × 5in² produced measurable surface temperature depressions of approximately 4–10°C during transient cooling, exceeding the effective noise floor of the camera by more than two standard deviations. Thicker laminates exhibited prolonged defect detectability windows due to increased thermal diffusion time. In contrast, embedded Teflon inclusions generated weak thermal contrasts of ≤ 3°C, approaching the measurement noise floor, due to limited thermal property contrast with the surrounding glass fiber composite. These results establish quantitative detectability limits for stationary thermographic inspection of sandwich composite panels under manufacturing-representative thermal cycles.

Barakat, Abdallah [ORNL] (ORCID:0000000296141398)↗