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Perivascular macrophages (PVMs) and, to a lesser degree, microglia are targets and reservoirs of HIV and simian immunodeficiency virus (SIV) in the brain. Previously, we demonstrated that colony-stimulating factor 1 receptor (CSF1R) in PVMs was upregulated and activated in chronically SIV-infected rhesus macaques with encephalitis, correlating with SIV infection of PVMs. Herein, we investigated the role of CSF1R in the brain during acute SIV infection using BLZ945, a brain-penetrant CSF1R kinase inhibitor. Apart from three uninfected historic controls, nine Indian rhesus macaques were infected acutely with SIVmac251 and divided into three groups (n = 3 each): an untreated control and two groups treated for 20-30 days with low- (10 mg/kg/day) or high- (30 mg/kg/day) dose BLZ945. With the high-dose BLZ945 treatment, there was a significant reduction in cells expressing CD163 and CD206 across all four brain areas examined, compared with the low-dose treatment and control groups. In 9 of 11 tested regions, tissue viral DNA (vDNA) loads were reduced by 95%-99% following at least one of the two doses, and even to undetectable levels in some instances. Decreased numbers of CD163+ and CD206+ cells correlated significantly with lower levels of vDNA in all four corresponding brain areas. In contrast, BLZ945 treatment did not significantly affect the number of microglia. Our results indicate that doses as low as 10 mg/kg/day of BLZ945 are sufficient to reduce the tissue vDNA loads in the brain with no apparent adverse effect. This study provides evidence that infected PVMs are highly sensitive to CSF1R inhibition, opening new possibilities to achieve viral clearance.

To reduce the losses caused by major power outages in power systems, a two-stage optimization method for black start of power systems is proposed using a multi-energy microgrid (MEMG) as a black-start source. First, the load-side integrated demand response and the operation characteristics of the electric, thermal, and gas physical energy storage devices in the MEMG are modeled as generalized energy storage. Next, a two-stage optimization model for black start of power systems using the multi-energy microgrid as a black-start source is proposed, with the first stage being the optimization sub-model for non-black-start source restoration path and the second stage being the black-start strategy optimization sub-model considering the power system and the MEMG. Then, a Dijkstra’s algorithm-based solution method for the first stage sub-model and a mixed integer quadratic programming-based solution method for the second stage sub-model are respectively proposed. Finally, a case study of a real regional power system in China is conducted to verify the effectiveness and advantages of the proposed black start optimization method.

HIV reservoirs are extremely stable and pose a tremendous challenge to clear HIV infection. Here, we demonstrate that activation of ISR/ATF4 signaling reverses HIV latency, which also selectively eliminates HIV+ cells in primary CD4+T cell model of latency without effect on HIV-negative CD4+T cells. The reduction of HIV+ cells is associated with apoptosis enhancement, but surprisingly is largely seen in HIV-infected cells in which gag-pol RNA transcripts are detected in HIV RNA-induced ATF4/IFIT signaling. In resting CD4+ (rCD4+) T cells isolated from people living with HIV on antiretroviral therapy, induction of ISR/ATF4 signaling reduced HIV reservoirs by depletion of replication-competent HIV without global reduction in the rCD4+ T cell population. These findings suggest that compromised ISR/ATF4 signaling maintains stable and quiescent HIV reservoirs whereas activation of ISR/ATF4 signaling results in the disruption of latent HIV and clearance of persistently infected CD4+T cells.

Abstract The integration of renewable energy into power grid planning poses significant challenges. In this investigation, planning strategies across eight key indicators encompassing economic, reliability, environmental, and adaptability are assessed. Leveraging the analytical hierarchy process alongside the entropy weight method, subjective and objective weights are ascertained and comprehensive weights with parsimonious discriminative data are synthesized. Scores for planning strategies are then derived utilizing these weights. To illustrate and validate the efficacy of the proposed methodology, it was applied to four schemes within the IEEE‐6 node system, incorporating wind and photovoltaic power plants.

In extreme scenarios， load aggregators may control the market to rake in excess profits. To address this， this paper proposes a market power assessment method for load aggregators considering multiple uncertainties under ice disasters. Firstly， the universal generating function （UGF） is used to describe uncertainties of faults on overhead lines and wind turbines under ice disasters. Secondly， by aggregating standard probabilistic functions of various uncertainties， the paper proposes a market power assessment operator to construct a market power assessment model for load aggregator nodes. Finally， based on the results of the clearance model， a spatiotemporal market power index system is constructed to identify key load aggregators with high market power levels and the corresponding critical periods. Case study results demonstrate that this method effectively quantifies the market power levels of load aggregators under ice disasters， and that load aggregators in regions with higher loads are more likely to exercise market power during severe icing periods.

Therapeutic strategies are being clinically tested either to eradicate latent HIV reservoirs or to achieve virologic control in the absence of antiretroviral therapy. Attaining this goal will require a consensus on how best to measure the numbers of persistently infected cells with the potential to cause viral rebound after antiretroviral-therapy cessation in assessing the results of cure-directed strategies in vivo. Current measurements assess various aspects of the HIV provirus and its functionality and produce divergent results. Here, we provide recommendations from the BEAT-HIV Martin Delaney Collaboratory on which viral measurements should be prioritized in HIV-cure-directed clinical trials.

The persistence of HIV reservoirs, including latently infected, resting CD4+ T cells, is the major obstacle to cure HIV infection. CD32a expression was recently reported to mark CD4+ T cells harboring a replication-competent HIV reservoir during antiretroviral therapy (ART) suppression. We aimed to determine whether CD32 expression marks HIV latently or transcriptionally active infected CD4+ T cells. Using peripheral blood and lymphoid tissue of ART-treated HIV+ or SIV+ subjects, we found that most of the circulating memory CD32+ CD4+ T cells expressed markers of activation, including CD69, HLA-DR, CD25, CD38, and Ki67, and bore a TH2 phenotype as defined by CXCR3, CCR4, and CCR6. CD32 expression did not selectively enrich for HIV- or SIV-infected CD4+ T cells in peripheral blood or lymphoid tissue; isolated CD32+ resting CD4+ T cells accounted for less than 3% of the total HIV DNA in CD4+ T cells. Cell-associated HIV DNA and RNA loads in CD4+ T cells positively correlated with the frequency of CD32+ CD69+ CD4+ T cells but not with CD32 expression on resting CD4+ T cells. Using RNA fluorescence in situ hybridization, CD32 coexpression with HIV RNA or p24 was detected after in vitro HIV infection (peripheral blood mononuclear cell and tissue) and in vivo within lymph node tissue from HIV-infected individuals. Together, these results indicate that CD32 is not a marker of resting CD4+ T cells or of enriched HIV DNA-positive cells after ART; rather, CD32 is predominately expressed on a subset of activated CD4+ T cells enriched for transcriptionally active HIV after long-term ART.

IntroductionOrgan-specific autoimmune diseases are believed to result from immune responses generated against self-antigens specific to each organ. However, when such responses target antigens expressed promiscuously in multiple tissues, then the immune-mediated damage may be wide spread.MethodsIn this report, we describe a mitochondrial protein, branched chain α-ketoacid dehydrogenase kinase (BCKDk ) that can act as a target autoantigen in the development of autoimmune inflammatory reactions in both heart and liver.ResultsWe demonstrate that BCKDk protein contains at least nine immunodominant epitopes, three of which, BCKDk 71-90, BCKDk 111-130 and BCKDk 141-160, were found to induce varying degrees of myocarditis in immunized mice. One of these, BCKDk 111-130, could also induce hepatitis without affecting lungs, kidneys, skeletal muscles, and brain. In immunogenicity testing, all three peptides induced antigen-specific T cell responses, as verified by proliferation assay and/or major histocompatibility complex class II/IAk dextramer staining. Finally, the disease-inducing abilities of BCKDk peptides were correlated with the production of interferon-γ, and the activated T cells could transfer disease to naive recipients.ConclusionsThe disease induced by BCKDk peptides could serve as a useful model to study the autoimmune events of inflammatory heart and liver diseases.

Gas-wave refrigerators are widely used devices that utilize gas pressure to produce wave motion inside an oscillating tube for high-power refrigeration. This paper manufactures the core component of gas-wave refrigerators—the oscillating tubes—using hub and blade brazing. The tensile strength and fatigue life of the brazed joints were obtained through experiments. A finite element simulation based on the cohesive zone model determined that the critical damage stress of the brazed-joint brazing seam was 525 MPa. Under cyclic displacements of U = [0.4 mm, 0.5 mm, 0.6 mm], the errors between the simulated and experimental values of fatigue life are 9.09%, 4.38%, and 4.44%, respectively, which verifies the accuracy of the VUMAT subroutine of the cyclic CZM. The fatigue life relationship formula for the butt-brazed joints was fitted as y = 5458.97 x − 3.545 . Through the simulation analysis of the impact of the butt-joint angles on the fatigue life of brazed joints, it was found that as the butt-joint angle increased, the fatigue damage decreased, and the fatigue life increased. A finite element model of an oscillating tube with a DN (Nominal Diameter) of 285 × 450 mm was established to analyze the fatigue life of the butt-brazed structure of the rotor blade. The fatigue life of the brazed structure with a butt-joint angle of α = 45° increased by over 102.92% than that of α = 0°. [ABSTRACT FROM AUTHOR]