614 research outputs found

    Convolution of chemoattractant secretion rate, source density, and receptor desensitization direct diverse migration patterns in leukocytes

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    Chemoattractants regulate diverse immunological, developmental, and pathological processes, but how cell migration patterns are shaped by attractant production in tissues remains incompletely understood. Using computational modeling and chemokine-releasing microspheres (CRMs), cell-sized attractant-releasing beads, we analyzed leukocyte migration in physiologic gradients of CCL21or CCL19 produced by beads embedded in 3D collagen gels. Individual T-cells that migrated into contact with CRMs exhibited characteristic highly directional migration to attractant sources independent of their starting position in the gradient (and thus independent of initial gradient strength experienced) but the fraction of responding cells was highly sensitive to position in the gradient. These responses were consistent with modeling calculations assuming a threshold absolute difference in receptor occupancy across individual cells of [similar]10 receptors required to stimulate chemotaxis. In sustained gradients eliciting low receptor desensitization, attracted T-cells or dendritic cells swarmed around isolated CRMs for hours. With increasing CRM density, overlapping gradients and high attractant concentrations caused a transition from local swarming to transient “hopping” of cells bead to bead. Thus, diverse migration responses observed in vivo may be determined by chemoattractant source density and secretion rate, which govern receptor occupancy patterns in nearby cells.National Institutes of Health (U.S.) (NIH EB007280)Howard Hughes Medical Institute (Investigator

    Technical Introduction of Wireless Mesh Network

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    Grounded Image Text Matching with Mismatched Relation Reasoning

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    This paper introduces Grounded Image Text Matching with Mismatched Relation (GITM-MR), a novel visual-linguistic joint task that evaluates the relation understanding capabilities of transformer-based pre-trained models. GITM-MR requires a model to first determine if an expression describes an image, then localize referred objects or ground the mismatched parts of the text. We provide a benchmark for evaluating pre-trained models on this task, with a focus on the challenging settings of limited data and out-of-distribution sentence lengths. Our evaluation demonstrates that pre-trained models lack data efficiency and length generalization ability. To address this, we propose the Relation-sensitive Correspondence Reasoning Network (RCRN), which incorporates relation-aware reasoning via bi-directional message propagation guided by language structure. RCRN can be interpreted as a modular program and delivers strong performance in both length generalization and data efficiency

    Dependence of quantum correlations of twin beams on pump finesse of optical parametric oscillator

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    The dependence of quantum correlation of twin beams on the pump finesse of an optical parametric oscillator is studied with a semi-classical analysis. It is found that the phase-sum correlation of the output signal and idler beams from an optical parametric oscillator operating above threshold depends on the finesse of the pump field when the spurious pump phase noise generated inside the optical cavity and the excess noise of the input pump field are involved in the Langevin equations. The theoretical calculations can explain the previously experimental results, quantitatively.Comment: 27 pages, 8 figure

    BMI, reproductive factors, and breast cancer molecular subtypes: A case-control study and meta-analysis

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    BACKGROUND: The effects of body mass index (BMI) and reproductive factors may vary among breast cancer molecular subtypes, evidence of which is lacking in East Asia. METHODS: From 2002 to 2010, 1256 breast cancer patients and 1416 healthy women were recruited. Anthropometric and reproductive factors were collected from medical charts. Breast cancer subtype was defined by ER, PR, and HER2 status. Polytomous logistic regression was used to evaluate associations between risk factors and breast cancer subtypes, with subgroup analysis by menopausal status. A meta-analysis of relevant published studies in East Asia was also performed. RESULTS: In our case-control study, late menarche was negatively associated with luminal tumor risk (Ptrend = 0.03). Higher BMI was associated with risk of both luminal and triple-negative tumors (Ptrend<0.001). Late age at first live birth was associated with a 1.41- to 2.08-fold increased risk of all subtypes, while late menopause increased risk by 2.62-5.56 times. Heterogeneity of these associations was not detected for different menopausal statuses. The meta-analysis revealed a positive dose-response relationship between BMI and risk of both luminal and ER-PR- subtypes (Ptrend<0.05). Early menarche and nulliparity increased luminal tumor risk by 1.39 and 1.26 times, respectively. Non-breastfeeding also increased the risk of all subtypes. CONCLUSIONS: For East Asian women, overweight, late menopause, and lack of breastfeeding appear to increase risk of both luminal and ER-PR- tumors. Early menarche and nulliparity mainly impacted luminal tumor risk. These associations were not impacted by menopausal status

    HSP27 Alleviates Cardiac Aging in Mice via a Mechanism Involving Antioxidation and Mitophagy Activation

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    Aging-induced cardiac dysfunction is a prominent feature of cardiac aging. Heat shock protein 27 (HSP27) protects cardiac function against ischemia or chemical challenge. We hypothesized that HSP27 attenuates cardiac aging. Transgenic (Tg) mice with cardiac-specific expression of the HSP27 gene and wild-type (WT) littermates were employed in the experiments. Echocardiography revealed a significant decline in the cardiac function of old WT mice compared with young WT mice. In striking contrast, the aging-induced impairment of cardiac function was attenuated in old Tg mice compared with old WT mice. Levels of cardiac aging markers were lower in old Tg mouse hearts than in old WT mouse hearts. Less interstitial fibrosis and lower contents of reactive oxygen species and ubiquitin-conjugated proteins were detected in old Tg hearts than in old WT hearts. Furthermore, old Tg hearts demonstrated lower accumulation of LC3-II and p62 than old WT hearts. Levels of Atg13, Vps34, and Rab7 were also higher in old Tg hearts than in old WT hearts. Additionally, old Tg hearts had higher levels of PINK1 and Parkin than old WT hearts, suggesting that mitophagy was activated in old Tg hearts. Taken together, HSP27 alleviated cardiac aging and this action involved antioxidation and mitophagy activation
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