Effects of TLCD with maneuverable flaps on vibration control of a SDOF structure

Tuned liquid column damper (TLCD) is a class of auxiliary damping device which is used to dissipate vibrational energy of structures when excited by dynamic loading. Damping control of TLCDs is an important parameter to achieve the maximum benefit of TLCDs when attached to the structure. Herein, a new method of controlling damping is proposed by installing maneuverable flaps into TLCD (TLCD + MF). The damping value of the TLCD is controlled by the closing angle of the flaps. This method is simple in concept, more applicable in construction, and it is an effort to make the TLCD more controllable, (i.e. semi-active). Dynamic characteristics of such TLCD + MF system are investigated in this study. It is observed that by increasing the closing angle, the damping ratio of the TLCD + MF system increases. In addition, it is found that the mistuning of frequency becomes ignorable below the closing angle of 50°. The efficiency of the TLCD + MF in reducing response of structures under harmonic excitation is also studied. It is shown that existence of the flaps improves the performance of combined structure and the TLCD + MF system in terms of damping ratio and structural responses. The TLCD + MF system with the closing angle of 50° reduces the acceleration and displacement responses about 20 % more than conventional TLCDs

The pseudokinase SgK223 promotes invasion of pancreatic ductal epithelial cells through JAK1/Stat3 signaling

Background: Characterization of molecular mechanisms underpinning development of pancreatic ductal adenocarcinoma (PDAC) may lead to the identification of novel therapeutic targets and biomarkers. SgK223, also known as Pragmin, is a pseudokinase and scaffolding protein closely related to SgK269/PEAK1. Both proteins are implicated in oncogenic tyrosine kinase signaling, but their mechanisms and function remain poorly characterized. Methods: Expression of SgK223 in PDAC and PDAC cell lines was characterized using gene expression microarrays, mass spectrometry (MS)-based phosphoproteomics and Western blotting. SgK223 was overexpressed in human pancreatic ductal epithelial (HPDE) cells via retroviral transduction, and knocked down in PDAC cells using siRNA. Cell proliferation was determined using a colorimetric cell viability assay, and cell migration and invasion using transwells. Expression of markers of epithelial-mesenchyme transition (EMT) was assayed by quantitative PCR. SgK223 and Stat3 signaling was interrogated by immunoprecipitation, Western blot and gene reporter assays. The functional role of specific kinases and Stat3 was determined using selective small molecule inhibitors. Results: Elevated site-selective tyrosine phosphorylation of SgK223 was identified in subsets of PDAC cell lines, and increased expression of SgK223 detected in several PDAC cell lines compared to human pancreatic ductal epithelial (HPDE) cells and in PDACs compared to normal pancreas. Expression of SgK223 in HPDE cells at levels comparable to those in PDAC did not alter cell proliferation but led to a more elongated morphology, enhanced migration and invasion and induced gene expression changes characteristic of a partial EMT. While SgK223 overexpression did not affect activation of Erk or Akt, it led to increased Stat3 Tyr705 phosphorylation and Stat3 transcriptional activity, and SgK223 and Stat3 associated in vivo. SgK223-overexpressing cells exhibited increased JAK1 activation, and use of selective inhibitors determined that the increased Stat3 signaling driven by SgK223 was JAK-dependent. Pharmacological inhibition of Stat3 revealed that Stat3 activation was required for the enhanced motility and invasion of SgK223-overexpressing cells. Conclusions: Increased expression of SgK223 occurs in PDAC, and overexpression of SgK223 in pancreatic ductal epithelial cells promotes acquisition of a migratory and invasive phenotype through enhanced JAK1/Stat3 signaling. This represents the first association of SgK223 with a particular human cancer, and links SgK223 with a major signaling pathway strongly implicated in PDAC progression

Serum Zinc Concentration and C-Reactive Protein in Individuals with Human Immunodeficiency Virus Infection: the Positive Living with HIV (POLH) Study

Low zinc levels and chronic inflammation are common in individuals infected with human immunodeficiency virus (HIV). Zinc deficiency may promote systemic inflammation, but research on the role of zinc in inflammation among HIV-positive individuals taking account of antiretroviral therapy is lacking. We assessed the association between serum zinc and C-reactive protein (CRP) concentration in a cohort of HIV-positive individuals. A cross-sectional survey was conducted among 311 HIV-positive individuals (177 men and 134 women) aged 18–60 years residing in Kathmandu, Nepal. High-sensitive or regular serum CRP concentrations were measured by the latex agglutination nephelometry or turbidimetric method, and zinc concentrations were measured by the atomic absorption method. Relationships were assessed using multiple linear regression analysis. The geometric means of zinc in men and women were 73.83 and 71.93 ug/dL, respectively, and of CRP were 1.64 and 0.96 mg/L, respectively. Mean serum CRP concentration was significantly decreased with increasing serum zinc concentration across zinc tertiles (P for trend=0.010), with mean serum CRP concentration in the highest tertile of serum zinc concentration was 44.2 % lower than that in the lowest tertile. The mean serum CRP concentrations in men and women in the highest tertile of serum zinc concentrations were 30 and 35.9% lower, respectively, than that in the lowest tertile (P for trend=0.263 and 0.162, respectively). We found a significant inverse relation between log zinc and log CRP concentrations (beta for 1 unit change in log zinc; β=−1.79, p=0.0003). Serum zinc concentration may be inversely associated with serum CRP concentration in HIV-positive individuals