Design and Analyses of a MEMS Based Resonant Magnetometer

A novel design of a MEMS torsional resonant magnetometer based on Lorentz force is presented and fabricated. The magnetometer consists of a silicon resonator, torsional beam, excitation coil, capacitance plates and glass substrate. Working in a resonant condition, the sensor’s vibration amplitude is converted into the sensing capacitance change, which reflects the outside magnetic flux-density. Based on the simulation, the key structure parameters are optimized and the air damping effect is estimated. The test results of the prototype are in accordance with the simulation results of the designed model. The resolution of the magnetometer can reach 30 nT. The test results indicate its sensitivity of more than 400 mV/μT when operating in a 10 Pa vacuum environment

Dissecting the γ\gamma-ray emissions of the nearby galaxies NGC 1068 and NGC 253

Intrigued by recent high-energy study results for nearby galaxies with gamma-ray emission and in particular NGC~1068 that has been detected as a neutrino-emitting source by the IceCube Neutrino Observatory, we conduct detailed analysis of the $\gamma$-ray data for the galaxies NGC~1068 and NGC~253, obtained with the Large Area Telescope onboard {\it the Fermi Gamma-ray Space Telescope}. By checking for their possible spectral features and then constructing light curves in corresponding energy ranges, we identify flare-like activity from NGC ~1068 in $\geq$2\,GeV energy range and significant long-term variations of NGC~253 in $\geq$5\,GeV energy range. In the former, the emission appears harder in the two half-year flare-like events than that in the otherwise `quiescent' state. In the latter, there is a 2-times decrease in the flux before and after MJD~57023, which is clearly revealed by the test-statistic maps we obtain. Considering studies carried out and models proposed for the $\gamma$-ray emissions of the two sources, we discuss the implications of our findings. The jet in NGC~1068 may contribute to the \gr\ emission. The nature of the long-term variations in NGC~253 is not clear, but the variation part of the emission may be connected to the very-high-energy (VHE) emission of the galaxy and could be verified by VHE observations.Comment: 9 pages, 6 figures, 2 tables, submitted to Ap

Systematic identification of genes involved in divergent skeletal muscle growth rates of broiler and layer chickens

<p>Abstract</p> <p>Background</p> <p>The genetic closeness and divergent muscle growth rates of broilers and layers make them great models for myogenesis study. In order to discover the molecular mechanisms determining the divergent muscle growth rates and muscle mass control in different chicken lines, we systematically identified differentially expressed genes between broiler and layer skeletal muscle cells during different developmental stages by microarray hybridization experiment.</p> <p>Results</p> <p>Taken together, 543 differentially expressed genes were identified between broilers and layers across different developmental stages. We found that differential regulation of slow-type muscle gene expression, satellite cell proliferation and differentiation, protein degradation rate and genes in some metabolic pathways could give great contributions to the divergent muscle growth rates of the two chicken lines. Interestingly, the expression profiles of a few differentially expressed genes were positively or negatively correlated with the growth rates of broilers and layers, indicating that those genes may function in regulating muscle growth during development.</p> <p>Conclusion</p> <p>The multiple muscle cell growth regulatory processes identified by our study implied that complicated molecular networks involved in the regulation of chicken muscle growth. These findings will not only offer genetic information for identifying candidate genes for chicken breeding, but also provide new clues for deciphering mechanisms underlining muscle development in vertebrates.</p

Dialysate glucose response phenotypes during peritoneal equilibration test and their association with cardiovascular death : a cohort study

Different measures of rates of transfer of glucose during the peritoneal equilibrium test (PET), undertaken during peritoneal dialysis (PD) might provide additional information regarding a patient's risk of future cardiovascular mortality. This study aimed to characterize the heterogeneity of dialysate glucose (DG) response phenotypes during the PET and compare the cardiovascular mortality rates associated with the different phenotypes. Our cohort was derived from Henan peritoneal dialysis registry. A total of 3477 patients initiating PD in 2007 to 2014 had the DG measured at 0, 2-hour and 4-hour (D0, D2, and D4 respectively) during the PET for estimation of D2/D0 and D4/D0. Deaths mainly due to CVD within 2 years since the initiation of PD were defined as the outcome. Latent class mixed-effect models were fitted to identify distinct phenotypes of the DG response during the PET. Multivariable unconditional Logistic regression models with adjustment for cardiometabolic risk factors were used to compare the 2-year risk of cardiovascular mortality among patients in the different latent classes. Three distinct DG response phenotypes during the PET were identified. Those with consistently high D2/D0 and D4/D0 ratios had a 1.22 [95% confidence interval: 1.02, 1.35] excess risk of a cardiovascular death within 2 years of commencing PD compared with patients with the lowest D2/D0 ratio and decreased D4/D0 ratio after adjustment for cardiometabolic risk factors. Consistently elevated D2/D0 and D4/D0 ratios during the PET are associated with an increased risk of 2-year cardiovascular mortality independent of other cardiometabolic risk factors. In view of the potential bias due to unmeasured confounders (eg, Family history of cardiovascular diseases, and dietary patterns), this association should be further validated in other external cohorts

Regeneration of Alveolar Type I and II Cells from Scgb1a1-Expressing Cells following Severe Pulmonary Damage Induced by Bleomycin and Influenza

The lung comprises an extensive surface of epithelia constantly exposed to environmental insults. Maintaining the integrity of the alveolar epithelia is critical for lung function and gaseous exchange. However, following severe pulmonary damage, what progenitor cells give rise to alveolar type I and II cells during the regeneration of alveolar epithelia has not been fully determined. In this study, we have investigated this issue by using transgenic mice in which Scgb1a1-expressing cells and their progeny can be genetically labeled with EGFP. We show that following severe alveolar damage induced either by bleomycin or by infection with influenza virus, the majority of the newly generated alveolar type II cells in the damaged parenchyma were labeled with EGFP. A large proportion of EGFP-expressing type I cells were also observed among the type II cells. These findings strongly suggest that Scgb1a1-expressing cells, most likely Clara cells, are a major cell type that gives rise to alveolar type I and II cells during the regeneration of alveolar epithelia in response to severe pulmonary damage in mice..Singapore. National Research FoundationSingapore–MIT Alliance for Research and Technology (Infectious Disease-IRG research programme

Metabolomics Investigation Reveals Metabolite Mediators Associated with Acute Lung Injury and Repair in a Murine Model of Influenza Pneumonia

Influenza virus infection (IVI) can cause primary viral pneumonia, which may progress to acute lung injury (ALI) and respiratory failure with a potentially fatal outcome. At present, the interactions between host and influenza virus at molecular levels and the underlying mechanisms that give rise to IVI-induced ALI are poorly understood. We conducted a comprehensive mass spectrometry-based metabolic profiling of serum, lung tissue and bronchoalveolar lavage fluid (BALF) from a non-lethal mouse model with influenza A virus at 0, 6, 10, 14, 21 and 28 days post infection (dpi), representing the major stages of IVI. Distinct metabolite signatures were observed in mice sera, lung tissues and BALF, indicating the molecular differences between systematic and localized host responses to IVI. More than 100 differential metabolites were captured in mice sera, lung tissues and BALF, including purines, pyrimidines, acylcarnitines, fatty acids, amino acids, glucocorticoids, sphingolipids, phospholipids, etc. Many of these metabolites belonged to pulmonary surfactants, indicating IVI-induced aberrations of the pulmonary surfactant system might play an important role in the etiology of respiratory failure and repair. Our findings revealed dynamic host responses to IVI and various metabolic pathways linked to disease progression, and provided mechanistic insights into IVI-induced ALI and repair process.National Science Foundation (U.S.)Singapore-MIT Alliance for Research and Technology (SMART

High-resolution HDX-MS reveals distinct mechanisms of RNA recognition and activation by RIG-I and MDA5

ABSTRACT RIG-I and MDA5 are the major intracellular immune receptors that recognize viral RNA species and undergo a series of conformational transitions leading to the activation of the interferon-mediated antiviral response. However, to date, full-length RLRs have resisted crystallographic efforts and a molecular description of their activation pathways remains hypothetical. Here we employ hydrogen/deuterium exchange coupled with mass spectrometry (HDX-MS) to probe the apo states of RIG-I and MDA5 and to dissect the molecular details with respect to distinct RNA species recognition, ATP binding and hydrolysis and CARDs activation. We show that human RIG-I maintains an auto-inhibited resting state owing to the intra-molecular HEL2i-CARD2 interactions while apo MDA5 lacks the analogous intra-molecular interactions and therefore adopts an extended conformation. Our work demonstrates that RIG-I binds and responds differently to short triphosphorylated RNA and long duplex RNA and that sequential addition of RNA and ATP triggers specific allosteric effects leading to RIG-I CARDs activation. We also present a high-resolution protein surface mapping technique that refines the cooperative oligomerization model of neighboring MDA5 molecules on long duplex RNA. Taken together, our data provide a high-resolution view of RLR activation in solution and offer new evidence for the molecular mechanism of RLR activation

Therapeutic Effects of Coccomyxagloeobotrydiformis on the Metabolic Syndrome in Rats

Background/Aims: The metabolic syndrome (MS) is a cluster of metabolic changes that carry a high risk of cardiovascular disease (CVD). A newly discovered microalga, coccomyxagloeobotrydiformis (CGD), has been reported to improve ischemic stroke and metabolism-related indicators. We observed the therapeutic effects of CGD on MS and postulated the underlying mechanism. Methods: A diet-induced MS model in rats was used to observe the therapeutic effects of CGD on MS. Blood-glucose and lipid indices were measured using enzymatic colorimetric kits. A biologic data acquisition and analysis system (BL-420F) was used to evaluate cardiac function. Expression of mitochondrial respiratory chain (MRC) enzymes was measured by immunofluorescence staining. The proteins associated with oxidative stress, apoptosis and inflammation were detected by western blotting. Results: Body weight, abdominal circumference, fasting blood glucose , blood pressure as well as serum levels of total cholesterol, triglycerides and low-density lipoprotein-cholesterol were decreased whereas serum levels of high-density lipoprotein-cholesterol was increased in CGD-treated MS rats. CGD increased left-ventricular systolic pressure, left-ventricular end-diastolic pressure, left-ventricular systolic pressure maximum rate of increase and left-ventricular diastolic pressure maximum rate of decrease in MS rats with cardiovascular complications. CGD up-regulated expression of adenosine monophosphate-activated protein kinase and peroxisome proliferator activated receptor gamma coactivator 1-alpha in the heart, adipose tissue and skeletal muscle. Expression of the MRC subunits of ATPase 6, cytochrome b and succinate dehydrogenase complex, subunit-A was increased whereas that of uncoupling protein-2 decreased in different tissues. CGD showed anti-oxidation effects by increasing expression of superoxide dismutase and decreasing that of malondialdehyde. High expression of Bcl-2 and low expression of Bax and caspase-3 supported the anti-apoptotic effect of CGD on the cardiovascular complications of MS. Conclusion: CGD has a therapeutic effect on MS and associated cardiovascular complications by eliciting mitochondrial protection and having anti-oxidation and anti-apoptosis effects. CGD could be used for MS treatment

Derivation and external validation of a risk prediction algorithm to estimate future risk of cardiovascular death among patients with type 2 diabetes and incident diabetic nephropathy: prospective cohort study

Objective To derive, and externally validate, a risk score for cardiovascular death among patients with type 2 diabetes and newly diagnosed diabetic nephropathy (DN). Research design and methods Two independent prospective cohorts with type 2 diabetes were used to develop and externally validate the risk score. The derivation cohort comprised 2282 patients with an incident, clinical diagnosis of DN. The validation cohort includes 950 patients with incident, biopsy-proven diagnosis of DN. The outcome was cardiovascular death within 2 years of the diagnosis of DN. Logistic regression was applied to derive the risk score for cardiovascular death from the derivation cohort, which was externally validated in the validation cohort. The score was also estimated by applying the United Kingdom Prospective Diabetes Study (UKPDS) risk score in the external validation cohort. Results The 2-year cardiovascular mortality was 12.05% and 11.79% in the derivation cohort and validation cohort, respectively. Traditional predictors including age, gender, body mass index, blood pressures, glucose, lipid profiles alongside novel laboratory test items covering five test panels (liver function, serum electrolytes, thyroid function, blood coagulation and blood count) were included in the final model. C-statistics was 0.736 (95% CI 0.731 to 0.740) and 0.747 (95% CI 0.737 to 0.756) in the derivation cohort and validation cohort, respectively. The calibration slope was 0.993 (95% CI 0.974 to 1.013) and 1.000 (95% CI 0.981 to 1.020) in the derivation cohort and validation cohort, respectively. The UKPDS risk score substantially underestimated cardiovascular mortality. Conclusions A new risk score based on routine clinical measurements that quantified individual risk of cardiovascular death was developed and externally validated. Compared with the UKPDS risk score, which underestimated the cardiovascular disease risk, the new score is a more specific tool for patients with type 2 diabetes and DN. The score could work as a tool to identify individuals at the highest risk of cardiovascular death among those with DN

Notch1 Pathway Protects against Burn-Induced Myocardial Injury by Repressing Reactive Oxygen Species Production through JAK2/STAT3 Signaling

Oxidative stress plays an important role in burn-induced myocardial injury, but the cellular mechanisms that control reactive oxygen species (ROS) production and scavenging are not fully understood. This study demonstrated that blockade of Notch signaling via knockout of the transcription factor RBP-J or a pharmacological inhibitor aggravated postburn myocardial injury, which manifested as deteriorated serum CK, CK-MB, and LDH levels and increased apoptosis in vitro and in vivo. Interruption of Notch signaling increased intracellular ROS production, and a ROS scavenger reversed the exacerbated myocardial injury after Notch signaling blockade. These results suggest that Notch signaling deficiency aggravated postburn myocardial injury through increased ROS levels. Notch signaling blockade also decreased MnSOD expression in vitro and in vivo. Notably, Notch signaling blockade downregulated p-JAK2 and p-STAT3 expression. Inhibition of JAK2/STAT3 signaling with AG490 markedly decreased MnSOD expression, increased ROS production, and aggravated myocardial injury. AG490 plus GSI exerted no additional effects. These results demonstrate that Notch signaling protects against burn-induced myocardial injury through JAK2/STAT3 signaling, which activates the expression of MnSOD and leads to decreased ROS levels