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

Genomic analysis of the function of the transcription factor gata3 during development of the Mammalian inner ear

We have studied the function of the zinc finger transcription factor gata3 in auditory system development by analysing temporal profiles of gene expression during differentiation of conditionally immortal cell lines derived to model specific auditory cell types and developmental stages. We tested and applied a novel probabilistic method called the gamma Model for Oligonucleotide Signals to analyse hybridization signals from Affymetrix oligonucleotide arrays. Expression levels estimated by this method correlated closely (p<0.0001) across a 10-fold range with those measured by quantitative RT-PCR for a sample of 61 different genes. In an unbiased list of 26 genes whose temporal profiles clustered most closely with that of gata3 in all cell lines, 10 were linked to Insulin-like Growth Factor signalling, including the serine/threonine kinase Akt/PKB. Knock-down of gata3 in vitro was associated with a decrease in expression of genes linked to IGF-signalling, including IGF1, IGF2 and several IGF-binding proteins. It also led to a small decrease in protein levels of the serine-threonine kinase Akt2/PKB beta, a dramatic increase in Akt1/PKB alpha protein and relocation of Akt1/PKB alpha from the nucleus to the cytoplasm. The cyclin-dependent kinase inhibitor p27(kip1), a known target of PKB/Akt, simultaneously decreased. In heterozygous gata3 null mice the expression of gata3 correlated with high levels of activated Akt/PKB. This functional relationship could explain the diverse function of gata3 during development, the hearing loss associated with gata3 heterozygous null mice and the broader symptoms of human patients with Hearing-Deafness-Renal anomaly syndrome

Therapeutic Effects of Liposome-Enveloped Ligusticum chuanxiong Essential Oil on Hypertrophic Scars in the Rabbit Ear Model

Hypertrophic scarring, a common proliferative disorder of dermal fibroblasts, results from an overproduction of fibroblasts and excessive deposition of collagen. Although treatment with surgical excision or steroid hormones can modify the symptoms, numerous treatment-related complications have been described. In view of this, we investigated the therapeutic effects of essential oil (EO) from rhizomes of Ligusticum chuanxiong Hort. (Umbelliferae) on formed hypertrophic scars in a rabbit ear model. EO was prepared as a liposomal formulation (liposome-enveloped essential oil, LEO) and a rabbit ear model with hypertrophic scars was established. LEO (2.5, 5, and 10%) was applied once daily to the scars for 28 days. On postoperative day 56, the scar tissue was excised for masson's trichrome staining, detection of fibroblast apoptosis, assays of the levels of collagens I and III, and analysis of the mRNA expression of matrix metalloproteinase-1 (MMP-1), caspase-3 and -9, and transforming growth factor beta 1 (TGF-β1). In addition, the scar elevation index (SEI) was also determined. As a result, LEO treatment significantly alleviated formed hypertrophic scars on rabbit ears. The levels of TGF-β1, MMP-1, collagen I, and collagen III were evidently decreased, and caspase -3 and -9 levels and apoptosis cells were markedly increased in the scar tissue. SEI was also significantly reduced. Histological findings exhibited significant amelioration of the collagen tissue. These results suggest that LEO possesses the favorable therapeutic effects on formed hypertrophic scars in the rabbit ear model and may be an effective cure for human hypertrophic scars

MiR-133a in Human Circulating Monocytes: A Potential Biomarker Associated with Postmenopausal Osteoporosis

Background: Osteoporosis mainly occurs in postmenopausal women, which is characterized by low bone mineral density (BMD) due to unbalanced bone resorption by osteoclasts and formation by osteoblasts. Circulating monocytes play important roles in osteoclastogenesis by acting as osteoclast precursors and secreting osteoclastogenic factors, such as IL-1, IL-6 and TNF-a. MicroRNAs (miRNAs) have been implicated as important biomarkers in various diseases. The present study aimed to find significant miRNA biomarkers in human circulating monocytes underlying postmenopausal osteoporosis. Methodology/Principal Findings: We used ABI TaqManH miRNA array followed by qRT-PCR validation in circulating monocytes to identify miRNA biomarkers in 10 high and 10 low BMD postmenopausal Caucasian women. MiR-133a was upregulated (P = 0.007) in the low compared with the high BMD groups in the array analyses, which was also validated by qRT-PCR (P = 0.044). We performed bioinformatic target gene analysis and found three potential osteoclast-related target genes, CXCL11, CXCR3 and SLC39A1. In addition, we performed Pearson correlation analyses between the expression levels of miR-133a and the three potential target genes in the 20 postmenopausal women. We did find negative correlations between miR-133a and all the three genes though not significant. Conclusions/Significance: This is the first in vivo miRNA expression analysis in human circulating monocytes to identif

Low Temperature Growth of In2O3and InN Nanocrystals on Si(111) via Chemical Vapour Deposition Based on the Sublimation of NH4Cl in In

Indium oxide (In2O3) nanocrystals (NCs) have been obtained via atmospheric pressure, chemical vapour deposition (APCVD) on Si(111) via the direct oxidation of In with Ar:10% O2at 1000 °C but also at temperatures as low as 500 °C by the sublimation of ammonium chloride (NH4Cl) which is incorporated into the In under a gas flow of nitrogen (N2). Similarly InN NCs have also been obtained using sublimation of NH4Cl in a gas flow of NH3. During oxidation of In under a flow of O2the transfer of In into the gas stream is inhibited by the formation of In2O3around the In powder which breaks up only at high temperatures, i.e.T > 900 °C, thereby releasing In into the gas stream which can then react with O2leading to a high yield formation of isolated 500 nm In2O3octahedrons but also chains of these nanostructures. No such NCs were obtained by direct oxidation forTG < 900 °C. The incorporation of NH4Cl in the In leads to the sublimation of NH4Cl into NH3and HCl at around 338 °C which in turn produces an efficient dispersion and transfer of the whole In into the gas stream of N2where it reacts with HCl forming primarily InCl. The latter adsorbs onto the Si(111) where it reacts with H2O and O2leading to the formation of In2O3nanopyramids on Si(111). The rest of the InCl is carried downstream, where it solidifies at lower temperatures, and rapidly breaks down into metallic In upon exposure to H2O in the air. Upon carrying out the reaction of In with NH4Cl at 600 °C under NH3as opposed to N2, we obtain InN nanoparticles on Si(111) with an average diameter of 300 nm

Anti-EGFR Antibody Efficiently and Specifically Inhibits Human TSC2−/− Smooth Muscle Cell Proliferation. Possible Treatment Options for TSC and LAM

BACKGROUND: Tuberous sclerosis complex (TSC), a tumor syndrome caused by mutations in TSC1 or TSC2 genes, is characterized by the development of hamartomas. We previously isolated, from an angiomyolipoma of a TSC2 patient, a homogenous population of smooth muscle-like cells (TSC2(-/-) ASM cells) that have a mutation in the TSC2 gene as well as TSC2 loss of heterozygosity (LOH) and consequently, do not produce the TSC2 gene product, tuberin. TSC2(-/-) ASM cell proliferation is EGF-dependent. METHODS AND FINDINGS: Effects of EGF on proliferation of TSC2(-/-) ASM cells and TSC2(-/-) ASM cells transfected with TSC2 gene were determined. In contrast to TSC2(-/-) ASM cells, growth of TSC2-transfected cells was not dependent on EGF. Moreover, phosphorylation of Akt, PTEN, Erk and S6 was significantly decreased. EGF is a proliferative factor of TSC2(-/-) ASM cells. Exposure of TSC2(-/-) ASM cells to anti-EGFR antibodies significantly inhibited their proliferation, reverted reactivity to HMB45 antibody, a marker of TSC2(-/-) cell phenotype, and inhibited constitutive phosphorylation of S6 and ERK. Exposure of TSC2(-/-) ASM cells to rapamycin reduced the proliferation rate, but only when added at plating time. Although rapamycin efficiently inhibited S6 phosphorylation, it was less efficient than anti-EGFR antibody in reverting HMB45 reactivity and blocking ERK phosphorylation. In TSC2(-/-) ASM cells specific PI3K inhibitors (e.g. LY294002, wortmannin) and Akt1 siRNA had little effect on S6 and ERK phosphorylation. Following TSC2-gene transfection, Akt inhibitor sensitivity was observed. CONCLUSION: Our results show that an EGF independent pathway is more important than that involving IGF-I for growth and survival of TSC(-/-) ASM cells, and such EGF-dependency is the result of the lack of tuberin

Modulation of microglia by Wolfberry on the survival of retinal ganglion cells in a rat ocular hypertension model

The active component of Wolfberry (Lycium barbarum), lycium barbarum polysaccharides (LBP), has been shown to be neuroprotective to retinal ganglion cells (RGCs) against ocular hypertension (OH). Aiming to study whether this neuroprotection is mediated via modulating immune cells in the retina, we used multiphoton confocal microscopy to investigate morphological changes of microglia in whole-mounted retinas. Retinas under OH displayed slightly activated microglia. One to 100 mg/kg LBP exerted the best neuroprotection and elicited moderately activated microglia in the inner retina with ramified appearance but thicker and focally enlarged processes. Intravitreous injection of lipopolysaccharide decreased the survival of RGCs at 4 weeks, and the activated microglia exhibited amoeboid appearance as fully activated phenotype. When activation of microglia was attenuated by intravitreous injection of macrophage/microglia inhibitory factor, protective effect of 10 mg/kg LBP was attenuated. The results implicated that neuroprotective effects of LBP were partly due to modulating the activation of microglia

Baculovirus Infection Triggers a Shift from Amino Acid Starvation-Induced Autophagy to Apoptosis

Autophagy plays a central role in regulating important cellular functions such as cell survival during starvation and control of infectious pathogens. On the other hand, many pathogens have evolved mechanisms of inhibition of autophagy such as blockage of the formation of autophagosomes or the fusion of autophagosomes with lysosomes. Baculoviruses are important insect pathogens for pest control, and autophagy activity increases significantly during insect metamorphosis. However, it is not clear whether baculovirus infection has effects on the increased autophagy. In the present study, we investigated the effects of the Autographa californica nucleopolyhedrovirus (AcMNPV) infection on autophagy in SL-HP cell line from Spodoptera litura induced under amino acid deprivation. The results revealed that AcMNPV infection did not inhibit autophagy but triggered apoptosis under starvation pressure. In the early stage of infection under starvation, mitochondrial dysfunction was detected, suggesting the organelles might be involved in cell apoptosis. The semi-quantitative PCR assay revealed that the expression of both p35 and ie-1 genes of AcMNPV had no significant difference between the starved and unstarved SL-HP cells. The western blot analysis showed that no cleavage of endogenous Atg6 occurred during the process of apoptosis in SL-HP cells. These data demonstrated that some permissive insect cells may defend baculovirus infection via apoptosis under starvation and apoptosis is independent of the cleavage of Atg6 in SL-HP cells

Hyperadiponectinemia enhances bone formation in mice

<p>Abstract</p> <p>Background</p> <p>There is growing evidence that adiponectin, a physiologically active polypeptide secreted by adipocytes, controls not only adipose tissue but also bone metabolism. However, a role for adiponectin in bone development remains controversial.</p> <p>Methods</p> <p>We therefore investigated the endocrine effects of adiponectin on bone metabolism using 12-week-old male transgenic (Ad-Tg) mice with significant hyperadiponectinemia overexpressing human full-length adiponectin in the liver.</p> <p>Results</p> <p>In Ad-Tg mice, the serum level of osteocalcin was significantly increased, but the levels of RANKL, osteoprotegerin, and TRAP5b were not. Bone mass was significantly greater in Ad-Tg mice with increased bone formation. In contrast, bone resorption parameters including the number of osteoclasts and eroded surface area did not differ between Ad-Tg and their littermates.</p> <p>Conclusions</p> <p>These findings demonstrate that hyperadiponectinemia enhances bone formation in mice.</p

Effects of Common Polymorphisms rs11614913 in miR-196a2 and rs2910164 in miR-146a on Cancer Susceptibility: A Meta-Analysis

BACKGROUND: MicroRNAs regulate gene expression at the post-transcriptional level and involved in diverse biological and pathological processes, including tumorigenesis. Rs11614913 in miR-196a2 and rs2910164 in miR-146a are shown to associate with increased/decreased cancer risk. We performed a meta-analysis to systematically summarize the possible association. METHODOLOGY/PRINCIPAL FINDINGS: We assessed published studies of the association between these microRNA polymorphisms and cancer risk from eleven studies with 16,771 subjects for miR-196a2 and from ten studies with 15,126 subjects for miR-146a. As for rs11614913, the contrast of homozygote (TT vs CC: OR = 0.92, 95% CI = 0.85-0.99, P(heterogeneity) = 0.45), allele (T vs C: OR = 0.96, 95% CI = 0.92-0.99, P(heterogeneity) = 0.61) and recessive model (OR = 0.90, 95% CI = 0.84-0.97, P(heterogeneity) = 0.50) produced statistically association. Subgroup analysis by ethnicity, statistically significantly decreased cancer risks were found among Asians for allele contrast (OR = 0.95, 95% CI = 0.90-0.99, P(heterogeneity) = 0.74) and the recessive genetic model (OR = 0.90, 95% CI = 0.82-0.98, P(heterogeneity) = 0.85). According to subgroup analysis by tumor types, the protective effect of C/T polymorphism was only found in breast cancer under allele contrast (T vs C: OR = 0.94, 95% CI = 0.88-0.99, P(heterogeneity) = 0.26). For rs2910164, no significant associations were found among overall analysis model with relatively large heterogeneity. Through the stratified analysis, heterogeneity decreased significantly. In the subgroup analyses by cancer types, the C allele of rs2910164 was associated with protection from digestive cancer in allele contrast (C vs G: OR = 0.86, 95% CI = 0.77-0.96, P(heterogeneity) = 0.51). CONCLUSIONS/SIGNIFICANCE: Our meta-analysis suggests that the rs11614913 most likely contributes to decreased susceptibility to cancer, especially in Asians and breast cancer. Besides, the C allele of the rs2910164 might be associated with a protection from digestive cancer