ARTEMIS INTERACTS WITH THE CUL4A UBIQUITIN E3 LIGASE COMPLEX AND REGULATES THE CELL CYCLE PROGRESSION

Artemis, a member of the SNM1 gene family, is one of the six known components of the non-homologous end joining pathway. It is a multifunctional phospho-protein that has been shown to be modified by the phosphatidylinositol 3-kinases (PIKs) DNA-PKcs, ATM and ATR in response to a variety of cellular stresses. Artemis has important roles in V(D)J recombination, DNA double strand breaks repair and damage-induced cell-cycle checkpoint regulation. The detailed mechanism by which Artemis mediates its functions in these cellular pathways needs to be further elucidated. My work presented here demonstrates a new function for Artemis in cell cycle regulation as a component of Cullin-based E3 ligase complex. I show that Artemis interacts with Cul4A-DDB1 ligase complex via a direct interaction with the substrate-specific receptor DDB2, and deletion mapping analysis shows that part of the Snm1 domain of Artemis is responsible for this interaction. Additionally, Artemis also interacts with p27, a substrate of Cul4A-DDB1 complex, and both DDB2 and Artemis are required for the degradation of p27 mediated by this complex. Furthermore, I show that the regulation of p27 by Artemis and DDB2 is critical for cell cycle progression in normally proliferating cells and in response to serum withdrawal. Finally, I provide evidence showing that Artemis may be also a part of other Cullin-based E3 ligase complexes, and it has a role in controlling p27 levels in response to different cellular stress, such as UV irradiation. These findings suggest a novel pathway to regulate p27 protein level and define a new function for Artemis as an effector of Cullin-based E3-ligase mediated ubiquitylation, and thus, a cell cycle regulator in proliferating cells

Thermal Analyses of Power Electronics Integrated with Vapour Chamber Cooling

Insulated gate bipolar transistor (IGBT) power module is used for power switching transistor devices in the power supply and motor control circuits in both hybrid electric vehicles and electric vehicles. The target of heat flux of IGBT is continuously increasing due to the demand for power rating improvements and miniaturisation. Without suitable efficient cooling technologies, excessively high temperature and uneven temperature distribution can cause high thermal stress, eventually leading to severe module failures. Therefore, highly efficient cooling solutions are highly required. Vapour chamber with phase change can provide quick heat transfer and low temperature gradient. This study proposes a new IGBT structure integrated with vapour chamber. The tests and simulation results indicate that the thermal and thermo-mechanical performances of IGBT integrated with vapour chamber are better than those of the IGBT with copper baseplate module. The thermal resistance between the junction and heat sink is reduced from 0.25 to 0.14 °C/W, and the temperature uniformity is greatly improved due to the phase change in the vapour chamber. The simulation also investigates the thermal stress distribution, deformation and thermal fatigue lifespan of IGBT power electronics module. A reduction of 21.8% in thermal stress and an increase of 9% in lifespan of Sn–3.5Ag solder are achieved

Cross-view Semantic Alignment for Livestreaming Product Recognition

Live commerce is the act of selling products online through live streaming. The customer's diverse demands for online products introduce more challenges to Livestreaming Product Recognition. Previous works have primarily focused on fashion clothing data or utilize single-modal input, which does not reflect the real-world scenario where multimodal data from various categories are present. In this paper, we present LPR4M, a large-scale multimodal dataset that covers 34 categories, comprises 3 modalities (image, video, and text), and is 50x larger than the largest publicly available dataset. LPR4M contains diverse videos and noise modality pairs while exhibiting a long-tailed distribution, resembling real-world problems. Moreover, a cRoss-vIew semantiC alignmEnt (RICE) model is proposed to learn discriminative instance features from the image and video views of the products. This is achieved through instance-level contrastive learning and cross-view patch-level feature propagation. A novel Patch Feature Reconstruction loss is proposed to penalize the semantic misalignment between cross-view patches. Extensive experiments demonstrate the effectiveness of RICE and provide insights into the importance of dataset diversity and expressivity. The dataset and code are available at https://github.com/adxcreative/RICEComment: Accepted to ICCV202

Emergence of a STAT3 mutated NK clone in LGL leukemia

AbstractLarge granular lymphocyte (LGL) leukemia is a chronic clonal lymphoproliferative disorder. Here, a T-LGL leukemia patient developed NK-LGL leukemia with residual leukemic T-LGL. TCRVβ usage and CDR3 sequence drifts were observed with disease progression. A STAT3 S614R mutation was identified in NK but not T-cells in the mixed leukemic stage. Multiple, non-dominant T-cell clones with distinct STAT3 mutations were present throughout. Our results suggest that T and NK-LGL leukemia may share common pathogenesis mechanisms and that STAT3 mutation alone is insufficient to bring about clonal expansion. Mutational and immunological monitoring may provide diagnostic and therapeutic significance in LGL leukemia

Strain driven onset of non-trivial topological insulating states in Zintl Sr2X_2X compounds (XX=Pb, Sn)

We explore the topological behavior of the binary Zintl phase of the alkaline earth metals based compounds Sr$_2$Pb and Sr$_2$Sn using both standard and hybrid density functional theory. It is found that Sr$_2$Pb lies on the verge of a topological instability which can be suitably tuned through the application of a small uniaxial expansion strain ($>$ 3%). The resulting non-trivial topologically insulating state display well-defined metallic states in the Sr$_{2}$Pb(010) surface, whose evolution is studied as a function of the film thickness.Comment: 5 pages, 4 figure

The Correlation Between SPP1 and Immune Escape of EGFR Mutant Lung Adenocarcinoma Was Explored by Bioinformatics Analysis

BackgroundImmune checkpoint inhibitors have achieved breakthrough efficacy in treating lung adenocarcinoma (LUAD) with wild-type epidermal growth factor receptor (EGFR), leading to the revision of the treatment guidelines. However, most patients with EGFR mutation are resistant to immunotherapy. It is particularly important to study the differences in tumor microenvironment (TME) between patients with and without EGFR mutation. However, relevant research has not been reported. Our previous study showed that secreted phosphoprotein 1 (SPP1) promotes macrophage M2 polarization and PD-L1 expression in LUAD, which may influence response to immunotherapy. Here, we assessed the role of SPP1 in different populations and its effects on the TME.MethodsWe compared the expression of SPP1 in LUAD tumor and normal tissues, and in samples with wild-type and mutant EGFR. We also evaluated the influence of SPP1 on survival. The LUAD data sets were downloaded from TCGA and CPTAC databases. Clinicopathologic characteristics associated with overall survival in TCGA were assessed using Cox regression analysis. GSEA revealed that several fundamental signaling pathways were enriched in the high SPP1 expression group. We applied CIBERSORT and xCell to calculate the proportion and abundance of tumor-infiltrating immune cells (TICs) in LUAD, and compared the differences in patients with high or low SPP1 expression and wild-type or mutant EGFR. In addition, we explored the correlation between SPP1 and CD276 for different groups.ResultsSPP1 expression was higher in LUAD tumor tissues and in people with EGFR mutation. High SPP1 expression was associated with poor prognosis. Univariate and multivariate cox analysis revealed that up-regulated SPP1 expression was independent indicator of poor prognosis. GSEA showed that the SPP1 high expression group was mainly enriched in immunosuppressed pathways. In the SPP1 high expression group, the infiltration of CD8+ T cells was lower and M2-type macrophages was higher. These results were also observed in patients with EGFR mutation. Furthermore, we found that the SPP1 expression was positively correlated with CD276, especially in patients with EGFR mutation.ConclusionSPP1 levels might be a useful marker of immunosuppression in patients with EGFR mutation, and could offer insight for therapeutics