Search Results (649)

The negative strand of the human immunodeficiency virus-1 (HIV-1) proviral genome contains an antisense open reading frame encoding a protein (ASP) with no known homologs. The presence of immune responses to ASP in people living with HIV-1 (PLWH) demonstrates its expression in vivo. Further, the predicted hydrophobicity of ASP is consistent with its association with the plasma membrane and viral envelope. Despite this body of evidence, the role of ASP in HIV-1 replication remains unknown. In this report, we investigated the hypothesis that the presence of ASP on the viral surface enhances HIV-1 entry into target cells. We generated an ASP-knockout replication-competent HIV-1 molecular clone in the NL4-3 background, which we used to perform cell–cell fusion, viral entry, and viral replication assays. Our results suggest that the presence of ASP on the plasma membrane of infected cells and the envelope of HIV-1 virions enhances viral transmission. Overall, our studies provide first evidence that ASP plays a role in the HIV-1 replication cycle. Further investigation into these observations may lead to the identification of new HIV-1 vulnerabilities that may be the target of novel interventions. Full article

In tokamak-based nuclear fusion systems, powering the coils to control the plasma is a challenge that involves design choices that are a mix between advanced and traditional approaches. Each tokamak coil requires peculiar driving conditions and needs specific design activities. This paper deals with power supply design assessment for the Divertor (DIV) Coils in the Divertor Tokamak Test (DTT) facility. The design constraints of high-current (5500 A) and relatively low-voltages lead to the comparison of an SCR-based AC–AC converter (cycloconverter) with an IGBT-based DC–AC inverter with devices in a parallel solution and with interleaved modulation. The design assessment of two converter solutions to drive the DIV coils with the control issues were explored and described. Several simulation results were carried out to define the DIV coils operative conditions. Furthermore, an electro-thermal analysis on the used IGBT or thyristor devices was carried out considering the losses and the highest temperatures obtained in the conditions of maximum stress for the components. Full article

The pursuit of compact and efficient fusion energy systems necessitates innovative structural concepts capable of withstanding extreme operational conditions. This study presents a preliminary structural evaluation and stress assessment of a bucked-and-wedged configuration for the EU DEMO tokamak, targeting a peak magnetic field of 16.5 T. The proposed concept leverages mutual wedging of the Toroidal Field (TF) coils and their interaction with the Central Solenoid (CS) to optimize stress distribution in the inner legs, a critical region in high-field fusion reactors. To address the significant tangential forces arising during plasma operation, the design integrates outer inter-coil structures and shear pins to enhance mechanical stability. A hybrid simulation approach—coupling 3D electromagnetic and structural finite element analyses—is employed to assess stress behavior and structural integrity under both in-plane and out-of-plane loading conditions. The results contribute to the optimization study of high-field fusion reactor components and offer insights into viable mechanical design strategies for next-generation nuclear energy systems. Full article

Background: Blood-based comprehensive genomic profiling (CGP), a form of liquid biopsy, is often used for biliary tract cancer (BTC) when tissue-based CGP (tissue CGP) is unavailable, despite lower detection rates. This study explored factors linked to detecting actionable genomic alterations to optimize its use. Methods: We retrospectively analyzed BTC cases in Japan’s C-CAT (June 2019–January 2025), restricting panel comparisons to FoundationOne^® CDx (F1; n = 5019) and FoundationOne^® Liquid CDx (F1L; n = 1550). Missing covariates were handled by multiple imputations (m = 20). Between-panel balance used 1:1 propensity-score matching (caliper 0.2). Outcomes were modeled with logistic regression. Targets included MSI-H, TMB-H, FGFR2/RET/NTRK fusions, BRAF V600E, KRAS G12C, IDH1 mutations, and ERBB2 amplification. An exploratory analysis stratified results by the number of prespecified enrichment factors (0–4). Liquid biopsy was performed using plasma-based comprehensive genomic profiling assays (FoundationOne^® Liquid). Results: Missingness was low; after matching (n = 1549 per group) covariates were well balanced (all|SMD|≤0.05). Detection of any actionable alteration was lower with F1L than F1 (16.8% vs. 24.8%; OR 0.61, 95% CI 0.49–0.75; p < 0.001). F1L also had lower TMB-H (OR 0.62, 0.43–0.90; p = 0.01) and ERBB2 amplification (OR 0.42, 0.31–0.57; p < 0.001), with no significant differences for MSI-H, IDH1, KRAS G12C, or BRAF V600E. Within F1L, non-perihilar location (OR 2.05), liver (1.90), lymph-node (1.41), and lung metastases (1.52) predicted detection of actionable genomic alterations. F1L detection increased from 5.8% (zero factors) to 32.8% (four factors), approximating tissue at three factors. Conclusions: The utility of liquid biopsy can be maximized by carefully selecting samples on the basis of conditions that increase the detection rate. Full article

This study evaluates the application of metal additive manufacturing—specifically the laser powder bed fusion (LPBF) process—for producing aluminium die-casting mould components, comparing 300-grade maraging steel inserts with conventional H13 tool steel. Efficient thermal management and mould durability are critical in aluminium injection moulding. Still, traditional machining limits the design of cooling channels, resulting in hot spots, accelerated wear, and a reduced service life. LPBF allows the fabrication of complex geometries, enabling conformal cooling channels to enhance thermal control. Component samples were manufactured using maraging steel via LPBF, machined to final dimensions, and subjected to duplex surface treatment (plasma nitriding + CrAlN PVD coating). Thermal performance, dimensional stability, mechanical properties, and wear resistance were experimentally assessed under conditions simulating industrial production. The results demonstrate that LPBF components with optimised cooling channels and surface engineering achieve higher thermal efficiency, an extended service life (up to 2.6×), improved hardness profiles (545 HV0.05 core, 1230 HV0.05 on nitrided surface and 2850 HV0.05 after PVD film deposition), and reduced maintenance frequencies compared to H13 inserts. The study confirms that additive manufacturing, combined with tailored surface treatments and optimised cooling design, overcomes the geometric and thermal limitations of conventional manufacturing, offering a reliable and productive solution for aluminium die-casting moulds. Full article

Background: Polybasic peptides are being developed as components of reagents for diagnosing and treating patients with systemic amyloidosis. In addition to fibrils, amyloid deposits ubiquitously contain heparan sulfate proteoglycans. We have hypothesized that pan amyloid-targeting peptides can specifically engage, in addition to fibrils, a subset of glycosaminoglycans (GAGs) with high negative charge density. In this study, we characterized the binding of peptides p5+14 (a PET imaging agent for amyloid [¹²⁴I-evuzamitide]) and p5R (a fusion protein used in the therapeutic AT-02) to GAGs. Methods: The peptide structure was evaluated in the presence of low molecular weight heparin using circular dichroism, and their interaction with synthetic GAGs of varying length and charge was interrogated. The binding patterns of p5+14 and p5R were compared using correlation analyses. Results: The peptides exist as mixed structural-fractions in solution but adopt an α-helical structure in the presence of heparin. Both peptides preferentially recognize heparin and heparan sulfate GAGs with a linear positive correlation between binding and the total charge and charge density. Conclusions: These peptides have previously been shown to specifically target amyloid deposits in vivo. A component of this specificity is their preferential interaction with a subset of heparan sulfate GAGs that have high charge density, potentially related to the degree of 6-O-sulfation. These data support the hypotheses that amyloid-associated GAGs have unique sulfation patterns, thereby explaining why these peptides do not bind GAGs found on the plasma membrane and extracellular matrix of healthy tissues. Full article

A data set on Stark broadening parameters defining the Lorentzian line profile (spectral line widths and shifts) for 31 multiplets of four-times-charged nitrogen ion (N V), with lines broadened by impacts with electrons (e), protons (p), He II ions, $\alpha$ particles (He III), and B III, B IV, B V, and B VI ions, is given. The above-mentioned data have been calculated within the frame of the semiclassical perturbation theory, for temperatures from 50,000 K to 1,000,000 K, and densities of perturbers from 10¹⁵ cm⁻³ up to 10²¹ cm⁻³. These data are, first of all, of interest for diagnostics and modeling of laser-driven plasma in experiments and investigations of proton–boron fusion, especially when the target is boron nitride (BN). Data on Stark broadening by collisions with e, p, He II ions, and $\alpha$ particles are useful for the investigation of stellar plasma, in particular for white dwarf atmospheres and subphotospheric layer modeling. Full article

Electromagnetic implosions of hollow lithium cylinders can be utilized to compress magnetized plasma targets in the context of Magnetized Target Fusion (MTF). Two small-scale experiments were conducted at General Fusion as a stepping stone toward compressing magnetized plasmas on a larger scale. The first experiment is an electromagnetic implosion of a lithium ring, and the second is a compression of toroidal magnetic flux by imploding a hollow lithium cylinder onto an hourglass-shaped central structure. Here we present the methodology and results of modelling these experiments with OpenFOAM. Our in-house axisymmetric compressible MHD multi-phase solver was further extended to incorporate: (i) external RLC circuit model for electromagnetic compression coils and (ii) diffusion of the magnetic field into multiple solid materials. The implementation of the external RLC circuit model for electromagnetic coils was verified by comparison with results obtained with FEMM software and with the analytical solution. The solver was then applied to model both experiments and the main conclusions are as follows: (i) modelling solid lithium as a high-viscosity liquid is an adequate approach for the problems considered; (ii) the magnetic diffusivity of lithium is an important parameter for the accurate prediction of implosion trajectories (for the implosion of the lithium ring, higher values of magnetic diffusivity in the range $0.2 \le {\eta }_{\mathrm{ring}}[{\mathrm{m}}^2/\mathrm{s}] \le 0.5$ resulted in a better fit to the experimental data with a relative deviation in the trajectory of $\lesssim 20\%$); (iii) simulation results agree well with experimental data, and in particular, the toroidal field amplification of 2.25 observed in the experiment is reproduced in simulations within a relative error margin of 20%. The solver is proven to be robust and has the potential to be employed in a variety of applications. Full article

Tokamak technology, as the cornerstone of nuclear fusion energy, holds immense potential in achieving efficient plasma confinement and high energy densities. To comprehensively map the rapidly evolving landscape of this field, this study employs bibliometric analysis to systematically examine the research and development trends of tokamak technology from 2014 to 2024. The data are drawn from 7702 academic publications in the Scopus database, representing a global research effort. Additionally, the study incorporates 2299 tokamak-related patents from Google Patents over the same period, analyzing their technological trends to highlight the growing significance of tokamak devices. Using the R language and the Bibliometric package, the analysis explores research hotspots, institutional influences, and keyword evolution. The results reveal a multifaceted global landscape: China leads in publication output, and the United States maintains a leading role in citation impacts and technological innovation, with other notable contributions from Germany, Japan, South Korea, and various European countries. Patent trend analysis further reveals the rapid expansion of tokamak applications, particularly with significant innovations in high-temperature superconducting magnets and plasma control technologies. Nevertheless, the study identifies major challenges in the commercialization process, including plasma stability control, material durability, and the sustainability of long-term operations. To address these, the study proposes concrete future directions, emphasizing international collaboration and interdisciplinary integration. These efforts are crucial in accelerating tokamak commercialization, thereby providing a strategic roadmap for researchers, policymakers, and industry stakeholders to advance the global deployment of clean energy solutions. Full article

Volvariella volvacea, a fungal species of Volvariella within the Pluteaceae family, is predominantly cultivated in southern China. Polysaccharides, the primary bioactive constituents of V. volvacea, exhibit diverse pharmacological activities. However, current cultivation practices face challenges due to the genetic heterogeneity of strains, leading to inconsistent content and compositional variability of polysaccharides and other functional components. ARTP, denoting atmospheric and room-temperature plasma, is a technology capable of generating plasma jets at ambient pressure with temperatures ranging from 25 to 40 °C. These jets feature high concentrations of highly reactive species, including but not limited to excited-state helium atoms, oxygen atoms, nitrogen atoms, and OH radicals. This study aims to develop high-yielding exopolysaccharide (EPS) strains through integrated ARTP mutagenesis and genome shuffling, thereby overcoming current cultivation bottlenecks. ARTP mutagenesis and genome shuffling significantly boosted EPS production in V. volvacea. ARTP generated nine stable mutants with >20% higher EPS yields. Subsequent genome shuffling (three rounds of protoplast fusion) produced the hybrid strain SL212, which achieved 46.85 g/L of EPS, an 111.67% increase over that of the parent strain under identical conditions. Metabolomics and transcriptomics analyses revealed that differential metabolites and genes were mainly enriched in galactose metabolism, ABC transporter pathways, and the tricarboxylic acid cycle. These pathways enhance monosaccharide biosynthesis and generate ATP, providing both precursors and energy for polysaccharide polymerization, thereby driving EPS overproduction. Preliminary mechanistic analysis identified the key contributing factors driving the elevated polysaccharide biosynthesis. Full article

This study assesses how different anode materials influence neutron production rates (NPRs) in multi-state fusion (MSF) reactors, with a particular focus on the effects of deuterium (D) pre-loading on the anode surface. Three types of mesh anodes were assessed: stainless steel (SS), zirconium (Zr), and D pre-loaded zirconium (ZrD). MSF operates using two electrodes to confine ions to various fusion reactions, including D-D and D-T. The reactor features a negatively biased central cathode and a grounded anode within a vacuum vessel. Neutrons and protons are produced through the application of high voltage (tens of kV) and current (tens of mA) on the system to spark the plasma and start the fusion. Assessments at voltages up to 50 kV and currents up to 30 mA showed that Zr mesh anodes produced higher NPRs than SS ones, reaching 1.912 at 30 kV. This increased performance is attributed to surface fusion processes occurring in the anode. These processes were further modified by the deuterium pre-loading in the ZrD anode, as compared to SS and Zr with 1.832 at 30 kV. The findings suggest that material properties and deuterium pre-loading play significant roles in optimizing the efficiency of MSF reactors and the NPR. Future research may explore the long-term stability and durability of these anode materials under continuous operation conditions to fully harness their potential in fusion energy applications. Full article

Insulin-regulated glucose uptake is a central mechanism in maintaining systemic glucose homeostasis, primarily occurring in skeletal muscle and adipose tissue. This process relies on the insulin-stimulated translocation of the glucose transporter, GLUT4, from specialized intracellular compartments, known as GLUT4 storage vesicles (GSVs), to the plasma membrane. Disruption of this pathway is a hallmark of insulin resistance and a key contributor to the pathogenesis of type 2 diabetes. Recent advances have provided critical insights into both the insulin signalling cascades and the complex biogenesis, as well as the trafficking and fusion dynamics of GSVs. This review synthesizes the current understanding of the molecular mechanisms governing GSV mobilization and membrane fusion, highlighting key regulatory nodes that may become dysfunctional in metabolic disease. By elucidating these pathways, we propose new therapeutic avenues targeting GSV trafficking to improve insulin sensitivity and combat type 2 diabetes. Full article

Negative Ion Source Neutral beam Injection (NNBI), as a critical auxiliary heating system for magnetic confinement fusion devices, directly affects the plasma heating efficiency of tokamak devices through the reliability of its beam source system. The single-shot experiment constitutes a significant experimental program for NNBI. This study addresses the frequent equipment failures encountered by the NNBI beam source system during a cycle of experiments, employing fault tree analysis (FTA) to conduct a systematic reliability assessment. Utilizing the AutoFTA 3.9 software platform, a fault tree model of the beam source system was established. Minimal cut set analysis was performed to identify the system’s weak points. The research employed AutoFTA 3.9 for both qualitative analysis and quantitative calculations, obtaining the failure probabilities of critical components. Furthermore, the F-V importance measure and mean time between failures (MTBF) were applied to analyze the system. This provides a theoretical basis and practical engineering guidance for enhancing the operational reliability of the NNBI system. The evaluation methodology developed in this study can be extended and applied to the reliability analysis of other high-power particle acceleration systems. Full article

The Golgi of goblet cells represents a specialized machine for mucin glycosylation. This process occurs in a specialized form of the secretory pathway, which remains poorly examined. Here, using high-resolution three-dimensional electron microscopy (EM), EM tomography, serial block face scanning EM (SBF-SEM) and immune EM we analyzed the secretory pathway in goblet cells and revealed that COPII-coated buds on the endoplasmic reticulum (ER) are extremely rare. The ERES vesicles with dimensions typical for the COPII-dependent vesicles were not found. The Golgi is formed by a single cisterna organized in a spiral with characteristics of the cycloid surface. This ribbon has a shape of a cup with irregular perforations. The Golgi cup is filled with secretory granules (SGs) containing glycosylated mucins. Their diameter is close to 1 µm. The cup is connected with ER exit sites (ERESs) with temporal bead-like connections, which are observed mostly near the craters observed at the externally located cis surface of the cup. The craters represent conus-like cavities formed by aligned holes of gradually decreasing diameters through the first three Golgi cisternae. These craters are localized directly opposite the ERES. Clusters of the 52 nm vesicles are visible between Golgi cisternae and between SGs. The accumulation of mucin, started in the fourth cisternal layer, induces distensions of the cisternal lumen. The thickness of these distensions gradually increases in size through the next cisternal layers. The spherical distensions are observed at the edges of the Golgi cup, where they fuse with SGs and detach from the cisternae. After the fusion of SGs located just below the apical plasma membrane (APM) with APM, mucus is secreted. The content of this SG becomes less osmiophilic and the excessive surface area of the APM is formed. This membrane is eliminated through the detachment of bubbles filled with another SG and surrounded with a double membrane or by collapse of the empty SG and transformation of the double membrane lacking a visible lumen into multilayered organelles, which move to the cell basis and are secreted into the intercellular space where the processes of dendritic cells are localized. These data are evaluated from the point of view of existing models of intracellular transport. Full article

Helium (He) accumulation in tungsten—widely used as a plasma-facing material in fusion reactors—can lead to clustering, trap mutation, and eventual formation of helium bubbles, critically impacting material performance. To clarify the atomic-scale mechanisms governing this process, we conducted systematic molecular statics and molecular dynamics simulations across a wide range of vacancy cluster sizes (n = 1–27) and temperatures (500–2000 K). We identified the onset of trap mutation through abrupt increases in tungsten atomic displacement. At 0 K, the critical helium-to-vacancy (He/V) ratio required to trigger mutation was found to scale inversely with cluster size, converging to ~5.6 for large clusters. At elevated temperatures, thermal activation lowered the mutation threshold and introduced a distinct He/V stability window. Below this window, clusters tend to dissociate; above it, trap mutation occurs with near certainty. This critical He/V ratio exhibits a linear dependence on temperature and can be described by a size- and temperature-dependent empirical relation. Our results provide a quantitative framework for predicting trap mutation behavior in tungsten, offering key input for multiscale models and informing the design of radiation-resistant materials for fusion applications. Full article