Effects of seismic devices on transverse responses of piers in the Sutong Bridge

The Sutong Bridge in China opened to traffic in 2008, and is an arterial connection between the cities of Nantong and Suzhou. It is a cable-stayed bridge with a main span of 1,088 m. Due to a tight construction schedule and lack of suitable seismic devices at the time, fixed supports were installed between the piers and the girder in the transverse direction. As a result, significant transverse seismic forces could occur in the piers and foundations, especially during a return period of a 2500-year earthquake. Therefore, the piers, foundations and fixed bearings had to be designed extraordinarily strong. However, when larger earthquakes occur, the bearings, piers and foundations are still vulnerable. The recent rapid developments in seismic technology and the performance-based design approach offer a better opportunity to optimize the transverse seismic design for the Sutong Bridge piers. The optimized design can be applied to the Sutong Bridge (as a retrofit), as well as other bridges. Seismic design alternatives utilizing viscous fluid dampers (VFD), or friction pendulum sliding bearings (FPSB), or transverse yielding metallic dampers (TYMD) are thoroughly studied in this work, and the results are compared with those from the current condition with fixed transverse supports and a hypothetical condition in which only sliding bearings are provided on top of the piers (the girder can move “freely” in the transverse direction during the earthquake, except for frictional forces of the sliding bearings). Parametric analyses were performed to optimize the design of these proposed seismic devices. From the comparison of the peak bridge responses in these configurations, it was found that both VFD and TYMD are very effective in the reduction of transverse seismic forces in piers, while at the same time keeping the relative transverse displacements between piers and the box girder within acceptable limits. However, compared to VFD, TYMD do not interact with the longitudinal displacements of the girder, and have simpler details and lower initial and maintenance costs. Although the use of FPSB can also reduce seismic forces, it generally causes the transverse relative displacements to be higher than acceptable limits

Adaptation of Saccharomyces cerevisiae Cells to High Ethanol Concentration and Changes in Fatty Acid Composition of Membrane and Cell Size

BACKGROUND: Microorganisms can adapt to perturbations of the surrounding environment to grow. To analyze the adaptation process of the yeast Saccharomyces cerevisiae to a high ethanol concentration, repetitive cultivation was performed with a stepwise increase in the ethanol concentration in the culture medium. METHODOLOGY/PRINCIPAL FINDINGS: First, a laboratory strain of S. cerevisiae was cultivated in medium containing a low ethanol concentration, followed by repetitive cultivations. Then, the strain repeatedly cultivated in the low ethanol concentration was transferred to medium containing a high ethanol concentration and cultivated repeatedly in the same high-ethanol-concentration medium. When subjected to a stepwise increase in ethanol concentration with the repetitive cultivations, the yeast cells adapted to the high ethanol concentration; the specific growth rate of the adapted yeast strain did not decrease during repetitive cultivation in the medium containing the same ethanol concentration, while that of the non-adapted strain decreased during repetitive cultivation. A comparison of the fatty acid composition of the cell membrane showed that the contents in oleic acid (C(18:1)) in ethanol-adapted and non-adapted strains were similar, but the content of palmitic acid (C(16:0)) in the ethanol-adapted strains was lower than that in the non-adapted strain in media containing ethanol. Moreover, microscopic observation showed that the mother cells of the adapted yeast were significantly larger than those of the non-adapted strain. CONCLUSIONS: Our results suggest that activity of cell growth defined by specific growth rate of the yeast cells adapted to stepwise increase in ethanol concentration did not decrease during repetitive cultivation in high-ethanol-concentration medium. Moreover, fatty acid content of cell membrane and the size of ethanol-adapted yeast cells were changed during adaptation process. Those might be the typical phenotypes of yeast cells adapted to high ethanol concentration. In addition, the difference in sizes of the mother cell between the non-adapted and ethanol strains suggests that the cell size, cell cycle and adaptation to ethanol are thought to be closely correlated

Three-dimension structure of ventricular myocardial fibers after myocardial infarction

<p>Abstract</p> <p>Background</p> <p>To explore the pathological changes of three-dimension structure of ventricular myocardial fibers after anterior myocardial infarction in dog heart.</p> <p>Methods</p> <p>Fourteen acute anterior myocardial infarction models were made from healthy dogs (mean weight 17.6 ± 2.5 kg). Six out of 14 dogs with old myocardial infarction were sacrificed, and their hearts were harvested after they survived the acute anterior myocardial infarction for 3 months. Each heart was dissected into ventricular myocardial band (VMB), morphological characters in infarction region were observed, and infarct size percents in descending segment and ascending segment were calculated.</p> <p>Results</p> <p>Six dog hearts were successfully dissected into VMB. Uncorresponding damages in myocardial fibers of descending segment and ascending segment were found in apical circle in anterior wall infarction. Infarct size percent in the ascending segment was significantly larger than that in the descending segment (23.36 ± 3.15 (SD) vs 30.69 ± 2.40%, P = 0.0033); the long axis of infarction area was perpendicular to the orientation of myocardial fibers in ascending segment; however, the long axis of the infarction area was parallel with the orientation of myocardial fibers in descending segment.</p> <p>Conclusions</p> <p>We found that damages were different in both morphology and size in ascending segment and descending segment in heart with myocardial infarction. This may provide an important insight for us to understand the mechanism of heart failure following coronary artery diseases.</p

Dengue Dynamics in Binh Thuan Province, Southern Vietnam: Periodicity, Synchronicity and Climate Variability

Dengue has become a major international public health problem due to increasing geographic distribution and a transition from epidemic transmission with long inter-epidemic intervals to endemic transmission with seasonal fluctuation. Seasonal and multi-annual cycles in dengue incidence vary over time and space. We performed wavelet analyses on time series of monthly notified dengue cases in Binh Thuan province, southern Vietnam, from January 1994 to June 2009. We observed a continuous annual mode of oscillation with a non-stationary 2–3-year multi-annual cycle. We used phase differences to describe the spatio-temporal patterns which suggest that the seasonal wave of infection was either synchronous with all districts or moving away from Phan Thiet district, while the multi-annual wave of infection was moving towards Phan Thiet district. We also found a strong non-stationary association between ENSO indices and climate variables with dengue incidence. We provided insight in dengue population transmission dynamics over the past 14.5 years. Further studies on an extensive time series dataset are needed to test the hypothesis that epidemics emanate from larger cities in southern Vietnam

Treatment-Induced Tumor Dormancy through YAP-Mediated Transcriptional Reprogramming of the Apoptotic Pathway

Eradicating tumor dormancy that develops following epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) treatment of EGFR-mutant non-small cell lung cancer, is an attractive therapeutic strategy but the mechanisms governing this process are poorly understood. Blockade of ERK1/2 reactivation following EGFR TKI treatment by combined EGFR/MEK inhibition uncovers cells that survive by entering a senescence-like dormant state characterized by high YAP/TEAD activity. YAP/TEAD engage the epithelial-to-mesenchymal transition transcription factor SLUG to directly repress pro-apoptotic BMF, limiting drug-induced apoptosis. Pharmacological co-inhibition of YAP and TEAD, or genetic deletion of YAP1, all deplete dormant cells by enhancing EGFR/MEK inhibition-induced apoptosis. Enhancing the initial efficacy of targeted therapies could ultimately lead to prolonged treatment responses in cancer patients

Plasmid-based transient human stromal cell-derived factor-1 gene transfer improves cardiac function in chronic heart failure

We previously demonstrated that transient stromal cell-derived factor-1 alpha (SDF-1) improved cardiac function when delivered via cell therapy in ischemic cardiomyopathy at a time remote from acute myocardial infarction (MI) rats. We hypothesized that non-viral gene transfer of naked plasmid DNA-expressing hSDF-1 could similarly improve cardiac function. To optimize plasmid delivery, we tested SDF-1 and luciferase plasmids driven by the cytomegalovirus (CMV) promoter with (pCMVe) or without (pCMV) translational enhancers or α myosin heavy chain (pMHC) promoter in a rodent model of heart failure. In vivo expression of pCMVe was 10-fold greater than pCMV and pMHC expression and continued over 30 days. We directly injected rat hearts with SDF-1 plasmid 1 month after MI and assessed heart function. At 4 weeks after plasmid injection, we observed a 35.97 and 32.65% decline in fractional shortening (FS) in control (saline) animals and pMHC-hSDF1 animals, respectively, which was sustained to 8 weeks. In contrast, we observed a significant 24.97% increase in animals injected with the pCMVe-hSDF1 vector. Immunohistochemistry of cardiac tissue revealed a significant increase in vessel density in the hSDF-1-treated animals compared with control animals. Increasing SDF-1 expression promoted angiogenesis and improved cardiac function in rats with ischemic heart failure along with evidence of scar remodeling with a trend toward decreased myocardial fibrosis. These data demonstrate that stand-alone non-viral hSDF-1 gene transfer is a strategy for improving cardiac function in ischemic cardiomyopathy

A high-order FEM formulation for free and forced vibration analysis of a nonlocal nonlinear graded Timoshenko nanobeam based on the weak form quadrature element method

The purpose of this paper is to provide a high-order finite element method (FEM) formulation of nonlocal nonlinear nonlocal graded Timoshenko based on the weak form quadrature element method (WQEM). This formulation offers the advantages and flexibility of the FEM without its limiting low-order accuracy. The nanobeam theory accounts for the von Kármán geometric nonlinearity in addition to Eringen’s nonlocal constitutive models. For the sake of generality, a nonlinear foundation is included in the formulation. The proposed formulation generates high-order derivative terms that cannot be accounted for using regular first- or second-order interpolation functions. Hamilton’s principle is used to derive the variational statement which is discretized using WQEM. The results of a WQEM free vibration study are assessed using data obtained from a similar problem solved by the differential quadrature method (DQM). The study shows that WQEM can offer the same accuracy as DQM with a reduced computational cost. Currently the literature describes a small number of high-order numerical forced vibration problems, the majority of which are limited to DQM. To obtain forced vibration solutions using WQEM, the authors propose two different methods to obtain frequency response curves. The obtained results indicate that the frequency response curves generated by either method closely match their DQM counterparts obtained from the literature, and this is despite the low mesh density used for the WQEM systems

Aberrations of TACC1 and TACC3 are associated with ovarian cancer

BACKGROUND: Dysregulation of the human Transforming Acidic Coiled Coil (TACC) genes is thought to be important in the development and progression of multiple myeloma, breast and gastric cancer. Recent, large-scale genomic analysis and Serial Analysis of Gene Expression data suggest that TACC1 and TACC3 may also be involved in the etiology of ovarian tumors from both familial and sporadic cases. Therefore, the aim of this study was to determine the occurrence of alterations of these TACCs in ovarian cancer. METHODS: Detection and scoring of TACC1 and TACC3 expression was performed by immunohistochemical analysis of the T-BO-1 tissue/tumor microarray slide from the Cooperative Human Tissue Network, Tissue Array Research Program (TARP) of the National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. Tumors were categorized as either positive (greater than 10% of cells staining) or negative. Statistical analysis was performed using Fisher's exact test and p < 0.05 (single comparisons), and p < 0.02 (multiple comparisons) were considered to be significant. Transgenomics WAVE high performance liquid chromatography (dHPLC) was used to pre-screen the TACC3 gene in constitutional DNA from ovarian cancer patients and their unaffected relatives from 76 families from the Gilda Radner Familial Ovarian Cancer Registry. All variant patterns were then sequenced. RESULTS: This study demonstrated absence of at least one or both TACC proteins in 78.5% (51/65) of ovarian tumors tested, with TACC3 loss observed in 67.7% of tumors. The distribution pattern of expression of the two TACC proteins was different, with TACC3 loss being more common in serous papillary carcinoma compared with clear cell carcinomas, while TACC1 staining was less frequent in endometroid than in serous papillary tumor cores. In addition, we identified two constitutional mutations in the TACC3 gene in patients with ovarian cancer from the Gilda Radner Familial Ovarian Cancer Registry. These patients had previously tested negative for mutations in known ovarian cancer predisposing genes. CONCLUSION: When combined, our data suggest that aberrations of TACC genes, and TACC3 in particular, underlie a significant proportion of ovarian cancers. Thus, TACC3 could be a hitherto unknown endogenous factor that contributes to ovarian tumorigenesis

Investigating rare pathogenic/likely pathogenic exonic variation in bipolar disorder

Bipolar disorder (BD) is a serious mental illness with substantial common variant heritability. However, the role of rare coding variation in BD is not well established. We examined the protein-coding (exonic) sequences of 3,987 unrelated individuals with BD and 5,322 controls of predominantly European ancestry across four cohorts from the Bipolar Sequencing Consortium (BSC). We assessed the burden of rare, protein-altering, single nucleotide variants classified as pathogenic or likely pathogenic (P-LP) both exome-wide and within several groups of genes with phenotypic or biologic plausibility in BD. While we observed an increased burden of rare coding P-LP variants within 165 genes identified as BD GWAS regions in 3,987 BD cases (meta-analysis OR = 1.9, 95% CI = 1.3-2.8, one-sided p = 6.0 × 10-4), this enrichment did not replicate in an additional 9,929 BD cases and 14,018 controls (OR = 0.9, one-side p = 0.70). Although BD shares common variant heritability with schizophrenia, in the BSC sample we did not observe a significant enrichment of P-LP variants in SCZ GWAS genes, in two classes of neuronal synaptic genes (RBFOX2 and FMRP) associated with SCZ or in loss-of-function intolerant genes. In this study, the largest analysis of exonic variation in BD, individuals with BD do not carry a replicable enrichment of rare P-LP variants across the exome or in any of several groups of genes with biologic plausibility. Moreover, despite a strong shared susceptibility between BD and SCZ through common genetic variation, we do not observe an association between BD risk and rare P-LP coding variants in genes known to modulate risk for SCZ