A simulation study on the measurement of D0-D0bar mixing parameter y at BES-III

We established a method on measuring the \dzdzb mixing parameter $y$ for BESIII experiment at the BEPCII $e^+e^-$ collider. In this method, the doubly tagged $\psi(3770) \to D^0 \overline{D^0}$ events, with one $D$ decays to CP-eigenstates and the other $D$ decays semileptonically, are used to reconstruct the signals. Since this analysis requires good $e/\pi$ separation, a likelihood approach, which combines the $dE/dx$, time of flight and the electromagnetic shower detectors information, is used for particle identification. We estimate the sensitivity of the measurement of $y$ to be 0.007 based on a $20fb^{-1}$ fully simulated MC sample.Comment: 6 pages, 7 figure

Angiotensin-Converting Enzyme-2 Overexpression Improves Left Ventricular Remodeling and Function in a Rat Model of Diabetic Cardiomyopathy

ObjectivesThe aim of this study was to test the hypothesis that angiotensin (Ang)-converting enzyme-2 (ACE2) overexpression may inhibit myocardial collagen accumulation and improve left ventricular (LV) remodeling and function in diabetic cardiomyopathy.BackgroundHyperglycemia activates the renin-Ang system, which promotes the accumulation of extracellular matrix and progression of cardiac remodeling and dysfunction.MethodsNinety male Wistar rats were divided randomly into treatment (n = 80) and control (n = 10) groups. Diabetes was induced in the treatment group by a single intraperitoneal injection of streptozotocin. Twelve weeks after streptozotocin injection, rats in the treatment group were further divided into adenovirus-ACE2, adenovirus–enhanced green fluorescent protein, losartan, and mock groups (n = 20 each). LV volume; LV systolic and diastolic function; extent of myocardial fibrosis; protein expression levels of ACE2, Ang-converting enzyme, and Ang-(1-7); and matrix metalloproteinase–2 activity were evaluated. Cardiac myocyte and fibroblast culture was performed to assess Ang-II and collagen protein expression before and after ACE2 gene transfection.ResultsFour weeks after ACE2 gene transfer, the adenovirus-ACE2 group showed increased ACE2 expression, matrix metalloproteinase–2 activity, and LV ejection fractions and decreased LV volumes, myocardial fibrosis, and ACE, Ang-II, and collagen expression in comparison with the adenovirus–enhanced green fluorescent protein and control groups. ACE2 was superior to losartan in improving LV remodeling and function and reducing collagen expression. The putative mechanisms may involve a shift in balance toward an inhibited fibroblast-myocyte cross-talk for collagen and transforming growth factor–beta production and enhanced collagen degradation by matrix metalloproteinase–2.ConclusionsACE2 inhibits myocardial collagen accumulation and improves LV remodeling and function in a rat model of diabetic cardiomyopathy. Thus, ACE2 provides a promising approach to the treatment of patients with diabetic cardiomyopathy

Angiotensin-Converting Enzyme (ACE) Gene Insertion/Deletion Polymorphism and ACE Inhibitor-Related Cough: A Meta-Analysis

Objective: An insertion/deletion (I/D) variant in the angiotensin-converting enzyme (ACE) gene was associated with ACE inhibitor (ACEI)-related cough in previous studies. However, the results were inconsistent. Our objective was to assess the relationship between the ACE I/D polymorphism and ACEI-related cough by meta-analysis and to summarize all studies that are related to ACE I/D polymorphism and ACEI-cough and make a summary conclusion to provide reference for the researchers who attempt to conduct such a study. Methods: Databases including PubMed, EMbase, Cochrane Library, and China National Knowledge Infrastructure, were searched for genetic association studies. Data were extracted by two independent authors and pooled odds ratio (OR) with 95% confidence interval (CI) was calculated. Metaregression and subgroup analyses were performed to identify the source of heterogeneity. Results: Eleven trials, including 906 cases (ACEI-related cough) and 1,175 controls, were reviewed in the present meta-analysis. The random effects pooled OR was 1.16 (95% CI: 0.78-1.74, p = 0.46) in the dominant model and 1.61 (95% CI: 1.18-2.20, p = 0.003) in the recessive model. Heterogeneity was found among and within studies. Metaregression indicated that the effect size was positively associated with age and negatively associated with follow-up duration of ACEI treatment. Subgroup analysis revealed a significant association between ACE I/D polymorphism and ACEI-related cough in studies with mean age >60 y, but not in studies with mean age 2 mo or in studies in Caucasians. No heterogeneity was detected in these two subgroups. Conclusions: Synthesis of the available evidence supports ACE I/D polymorphism as an age-dependent predictor for risk of ACEI-related cough

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Intermedin attenuates high-glucose exacerbated simulated hypoxia/reoxygenation injury in H9c2 cardiomyocytes via ERK1/2 signaling

Objective: This study investigated whether and how intermedin (IMD) exerted a protective effect against simulated hypoxia/reoxygenation (H/R) injury in high-glucose-treated H9c2 cells. Methods: Cellular viability was assessed via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. Oxidative stress was determined by malondialdehyde and superoxide dismutase content in the culture medium supernatant. Flow cytometry with Annexin V/propidium iodide staining was used to detect the cardiomyocyte apoptosis rate. The protein expression of Bax, Bcl-2, caspase-3, and ERK1/2 was determined by western blot. Results: IMD administration to H9c2 cells during H/R injury decreased oxidative stress product generation and inhibited apoptosis ( P < 0.05 or P < 0.01) while these effects were blocked by the ERK1/2 inhibitor ( P < 0.05 or P < 0.01). Through the application of a specific ERK1/2 inhibitor, it was demonstrated that IMD mitigates high-glucose-induced oxidative stress and apoptosis via ERK1/2 signaling. Conclusion: Intermedin may be a novel therapeutic agent for mitigating diabetic cardiovascular injury in the clinical setting

Research progress in preparation and application of hemicellulose-based hydrogels

Hemicellulose-based hydrogels are three-dimensional networks formed by crosslinking hydrophilic polymers with tunable swelling behavior,acceptable biocompatibility and mechanical properties,and have received much attention in the field of soft materials especially in hemicellulose-based materials.Herein,recent advances and developments in hemicellulose-based hydrogels were reviewed.The preparation methods,mechanism of their gelation process,and the performance of the hemicellulose-based hydrogels were presented from both chemical and physical cross-linking approaches,while the differences in various initiation systems such as light,enzyme,microwave irradiation and glow discharge electrolysis plasma in chemical cross-linking were compared.The latest applications of hemicellulose-based hydrogels in drug-controlled release,wound dressing,water purification,3D printing dispersions, etc,were introduced, respectively.Finally,the challenges in the development of hemicellulose-based hydrogels were summarized briefly and future prospect was also given,which provides a reference for the synthesis of new hemicellulose-based hydrogels

Correlation between the High Density Lipoprotein and its Subtypes in Coronary Heart Disease

Background/Aims: To detect the changes of high density lipoprotein (HDL) and its subtypes in serum of patients with coronary heart disease (CHD). Methods: 337 hospitalized patients were selected from our hospital during August, 2014 - January, 2015, and divided into CHD group (n = 190) and control group (n = 127). Lipoprint lipoprotein analyzer was used to classify low density lipoprotein (LDL) particle size and its sub-components, as well as HDL particle size and its sub-components. The changes of the subtypes in patients with CHD were statistically analyzed. The possible mechanism was explored. Results: (1) Compared with the control group, the concentration of HDL in CHD patients reduced, HDLL significantly decreased (P S increased (P L had the most significant decreased; (3) HDL and all HDL subtypes were positively correlated with apolipoprotein A-I (apoA-I), of which, HDLL had the biggest correlation with apoA-I (P M had a maximum correlation with HDL (P Conclusion: HDL maturation disorders existed in the serum of CHD patients, HDLL may be protected factor for CHD, whose decrease was closely related wit the risk increase of CHD. The cardiovascular protection function of HDLL may be related with apoA-I content