Mantle Flow Underneath the South China Sea Revealed by Seismic Anisotropy

It Has Long Been Established that Plastic Flow in the Asthenosphere Interacts Constantly with the overlying Lithosphere and Plays a Pivotal Role in Controlling the Occurrence of Geohazards Such as Earthquakes and Volcanic Eruptions. Unfortunately, Accurately Characterizing the Direction and Lateral Extents of the Mantle Flow Field is Notoriously Difficult, Especially in Oceanic Areas Where Deployment of Ocean Bottom Seismometers (OBSs) is Expensive and Thus Rare. in This Study, by Applying Shear Wave Splitting Analyses to a Dataset Recorded by an OBS Array that We Deployed between Mid-2019 and Mid-2020 in the South China Sea (SCS), We Show that the Dominant Mantle Flow Field Has a NNW-SSE Orientation, Which Can Be Attributed to Mantle Flow Extruded from the Tibetan Plateau by the Ongoing Indian-Eurasian Collision. in Addition, the Results Suggest that E-W Oriented Flow Fields Observed in South China and the Indochina Peninsula Do Not Extend to the Central SCS

Sox2 Cooperates with Inflammation-Mediated Stat3 Activation in the Malignant Transformation of Foregut Basal Progenitor Cells

SummarySox2 regulates the self-renewal of multiple types of stem cells. Recent studies suggest it also plays oncogenic roles in the formation of squamous carcinoma in several organs, including the esophagus where Sox2 is predominantly expressed in the basal progenitor cells of the stratified epithelium. Here, we use mouse genetic models to reveal a mechanism by which Sox2 cooperates with microenvironmental signals to malignantly transform epithelial progenitor cells. Conditional overexpression of Sox2 in basal cells expands the progenitor population in both the esophagus and forestomach. Significantly, carcinoma only develops in the forestomach, where pathological progression correlates with inflammation and nuclear localization of Stat3 in progenitor cells. Importantly, co-overexpression of Sox2 and activated Stat3 (Stat3C) also transforms esophageal basal cells but not the differentiated suprabasal cells. These findings indicate that basal stem/progenitor cells are the cells of origin of squamous carcinoma and that cooperation between Sox2 and microenvironment-activated Stat3 is required for Sox2-driven tumorigenesis

Diabetic cardiomyopathy is associated with defective myocellular copper regulation and both defects are rectified by divalent copper chelation

BACKGROUND: Heart disease is the leading cause of death in diabetic patients, and defective copper metabolism may play important roles in the pathogenesis of diabetic cardiomyopathy (DCM). The present study sought to determine how myocardial copper status and key copper-proteins might become impaired by diabetes, and how they respond to treatment with the Cu (II)-selective chelator triethylenetetramine (TETA) in DCM. METHODS: Experiments were performed in Wistar rats with streptozotocin (STZ)-induced diabetes with or without TETA treatment. Cardiac function was analyzed in isolated-perfused working hearts, and myocardial total copper content measured by particle-induced x-ray emission spectroscopy (PIXE) coupled with Rutherford backscattering spectrometry (RBS). Quantitative expression (mRNA and protein) and/or activity of key proteins that mediate LV-tissue-copper binding and transport, were analyzed by combined RT-qPCR, western blotting, immunofluorescence microscopy, and enzyme activity assays. Statistical analysis was performed using Student’s t-tests or ANOVA and p-values of < 0.05 have been considered significant. RESULTS: Left-ventricular (LV) copper levels and function were severely depressed in rats following 16-weeks’ diabetes, but both were unexpectedly normalized 8-weeks after treatment with TETA was instituted. Localized myocardial copper deficiency was accompanied by decreased expression and increased polymerization of the copper-responsive transition-metal-binding metallothionein proteins (MT1/MT2), consistent with impaired anti-oxidant defences and elevated susceptibility to pro-oxidant stress. Levels of the high-affinity copper transporter-1 (CTR1) were depressed in diabetes, consistent with impaired membrane copper uptake, and were not modified by TETA which, contrastingly, renormalized myocardial copper and increased levels and cell-membrane localization of the low-affinity copper transporter-2 (CTR2). Diabetes also lowered indexes of intracellular (IC) copper delivery via the copper chaperone for superoxide dismutase (CCS) to its target cuproenzyme, superoxide dismutase-1 (SOD1): this pathway was rectified by TETA treatment, which normalized SOD1 activity with consequent bolstering of anti-oxidant defenses. Furthermore, diabetes depressed levels of additional intracellular copper-transporting proteins, including antioxidant-protein-1 (ATOX1) and copper-transporting-ATPase-2 (ATP7B), whereas TETA elevated copper-transporting-ATPase-1 (ATP7A). CONCLUSIONS: Myocardial copper deficiency and defective cellular copper transport/trafficking are revealed as key molecular defects underlying LV impairment in diabetes, and TETA-mediated restoration of copper regulation provides a potential new class of therapeutic molecules for DCM

A Novel Clinically Relevant Strategy to Abrogate Autoimmunity and Regulate Alloimmunity in NOD Mice

OBJECTIVE - To investigate a new clinically relevant immunoregulatory strategy based on treatment with murine Thymoglobulin mATG Genzyme and CTLA4-Ig in NOD mice to prevent alloand autoimmune activation using a stringent model of islet transplantation and diabetes reversal. RESEARCH DESIGN AND METHODS - Using allogeneic islet transplantation models as well as NOD mice with recent onset type 1 diabetes, we addressed the therapeutic efficacy and immunomodulatory mechanisms associated with a new immunoregulatory protocol based on prolonged low-dose mATG plus CTLA4-Ig. RESULTS - BALB/c islets transplanted into hyperglycemic NOD mice under prolonged mATG+CTLA4-Ig treatment showed a pronounced delay in allograft rejection compared with untreated mice (mean survival time: 54 vs. 8 days, P < 0.0001). Immunologic analysis of mice receiving transplants revealed a complete abrogation of autoimmune responses and severe downregulation of alloimmunity in response to treatment. The striking effect on autoimmunity was confirmed by 100% diabetes reversal in newly hyperglycemic NOD mice and 100% indefinite survival of syngeneic islet transplantation (NOD.SCID into NOD mice). CONCLUSIONS - The capacity to regulate alloimmunity and to abrogate the autoimmune response in NOD mice in different settings confirmed that prolonged mATG+CTLA4-Ig treatment is a clinically relevant strategy to translate to humans with type 1 diabetes

Anomalous stopping of laser-accelerated intense proton beam in dense ionized matter

Ultrahigh-intensity lasers (10$^{18}$-10$^{22}$W/cm$^{2}$) have opened up new perspectives in many fields of research and application [1-5]. By irradiating a thin foil, an ultrahigh accelerating field (10$^{12}$ V/m) can be formed and multi-MeV ions with unprecedentedly high intensity (10$^{10}$A/cm$^2$) in short time scale ($\sim$ps) are produced [6-14]. Such beams provide new options in radiography [15], high-yield neutron sources [16], high-energy-density-matter generation [17], and ion fast ignition [18,19]. An accurate understanding of the nonlinear behavior of beam transport in matter is crucial for all these applications. We report here the first experimental evidence of anomalous stopping of a laser-generated high-current proton beam in well-characterized dense ionized matter. The observed stopping power is one order of magnitude higher than single-particle slowing-down theory predictions. We attribute this phenomenon to collective effects where the intense beam drives an decelerating electric field approaching 1GV/m in the dense ionized matter. This finding will have considerable impact on the future path to inertial fusion energy.Comment: 8 pages, 4 figure

Energy loss enhancement of very intense proton beams in dense matter due to the beam-density effect

Thoroughly understanding the transport and energy loss of intense ion beams in dense matter is essential for high-energy-density physics and inertial confinement fusion. Here, we report a stopping power experiment with a high-intensity laser-driven proton beam in cold, dense matter. The measured energy loss is one order of magnitude higher than the expectation of individual particle stopping models. We attribute this finding to the proximity of beam ions to each other, which is usually insignificant for relatively-low-current beams from classical accelerators. The ionization of the cold target by the intense ion beam is important for the stopping power calculation and has been considered using proper ionization cross section data. Final theoretical values agree well with the experimental results. Additionally, we extend the stopping power calculation for intense ion beams to plasma scenario based on Ohm's law. Both the proximity- and the Ohmic effect can enhance the energy loss of intense beams in dense matter, which are also summarized as the beam-density effect. This finding is useful for the stopping power estimation of intense beams and significant to fast ignition fusion driven by intense ion beams

Target density effects on charge tansfer of laser-accelerated carbon ions in dense plasma

We report on charge state measurements of laser-accelerated carbon ions in the energy range of several MeV penetrating a dense partially ionized plasma. The plasma was generated by irradiation of a foam target with laser-induced hohlraum radiation in the soft X-ray regime. We used the tri-cellulose acetate (C$_{9}$H$_{16}$O$_{8}$) foam of 2 mg/cm$^{-3}$ density, and $1$-mm interaction length as target material. This kind of plasma is advantageous for high-precision measurements, due to good uniformity and long lifetime compared to the ion pulse length and the interaction duration. The plasma parameters were diagnosed to be T$_{e}$=17 eV and n$_{e}$=4 $\times$ 10$^{20}$ cm$^{-3}$. The average charge states passing through the plasma were observed to be higher than those predicted by the commonly-used semiempirical formula. Through solving the rate equations, we attribute the enhancement to the target density effects which will increase the ionization rates on one hand and reduce the electron capture rates on the other hand. In previsous measurement with partially ionized plasma from gas discharge and z-pinch to laser direct irradiation, no target density effects were ever demonstrated. For the first time, we were able to experimentally prove that target density effects start to play a significant role in plasma near the critical density of Nd-Glass laser radiation. The finding is important for heavy ion beam driven high energy density physics and fast ignitions.Comment: 7 pages, 4 figures, 35 conference

Association of Genetic Variants of Melatonin Receptor 1B with Gestational Plasma Glucose Level and Risk of Glucose Intolerance in Pregnant Chinese Women

BACKGROUND: This study aimed to explore the association of MTNR1B genetic variants with gestational plasma glucose homeostasis in pregnant Chinese women. METHODS: A total of 1,985 pregnant Han Chinese women were recruited and evaluated for gestational glucose tolerance status with a two-step approach. The four MTNR1B variants rs10830963, rs1387153, rs1447352, and rs2166706 which had been reported to associate with glucose levels in general non-pregnant populations, were genotyped in these women. Using an additive model adjusted for age and body mass index (BMI), association of these variants with gestational fasting and postprandial plasma glucose (FPG and PPG) levels were analyzed by multiple linear regression; relative risk of developing gestational glucose intolerance was calculated by logistic regression. Hardy-Weinberg Equilibrium was tested by Chi-square and linkage disequilibrium (LD) between these variants was estimated by measures of D' and r(2). RESULTS: In the pregnant Chinese women, the MTNR1B variant rs10830963, rs1387153, rs2166706 and rs1447352 were shown to be associated with the increased 1 hour PPG level (p=8.04 × 10(-10), 5.49 × 10(-6), 1.89 × 10(-5) and 0.02, respectively). The alleles were also shown to be associated with gestational glucose intolerance with odds ratios (OR) of 1.64 (p=8.03 × 10(-11)), 1.43 (p=1.94 × 10(-6)), 1.38 (p=1.63 × 10(-5)) and 1.24 (p=0.007), respectively. MTNR1B rs1387153, rs2166706 were shown to be associated with gestational FPG levels (p=0.04). Our data also suggested that, the LD pattern of these variants in the studied women conformed to that in the general populations: rs1387153 and rs2166706 were in high LD, they linked moderately with rs10830963, but might not linked with rs1447352;rs10830963 might not link with rs1447352, either. In addition, the MTNR1B variants were not found to be associated with any other traits tested. CONCLUSIONS: The MTNR1B is likely to be involved in the regulation of glucose homeostasis during pregnancy