Dynamic responses of cyclindrical lattice shell roofs under horizontal earthquake motions with arbitrary direction by shaking table test

p. 409-419This paper is intended as an investigation of the seismic response behavior of cylindrical lattice shell structures by shaking table tests. The seismic vibration tests are carried out using small scale models with shell span of 60 cm of cylindrical lattice shell roofs with substructure under horizontal motions in arbitrary direction. From the experimental results, the effects of difference of earthquake input direction and relationship between mechanical properties of roofs and substructures on response behavior of shell roofs are made clear. In addition, it is confirmed that the seismic response evaluation methods proposed in previous papers (Takeuchi et al. [1] ~ Takeuchi et al. [3]) apply to the responses subjected to earthquake motions with arbitrary direction.Kumagai, T.; Takeuchi, T.; Susuki, I.; Ogawa, T. (2009). Dynamic responses of cyclindrical lattice shell roofs under horizontal earthquake motions with arbitrary direction by shaking table test. Editorial Universitat Politècnica de València. http://hdl.handle.net/10251/653

A mid term comparison of open wedge high tibial osteotomy vs unicompartmental knee arthroplasty for medial compartment osteoarthritis of the knee

<p>Abstract</p> <p>Background</p> <p>The choice of surgical treatments for unicompartmental osteoarthritis (OA) of the knee is still somewhat controversial. Midterm results from cases treated using unicompartmental knee arthroplasty (UKA) or open wedge high tibial osteotomy (OWHTO) were evaluated retrospectively.</p> <p>Methods</p> <p>Twenty-seven knees of 24 patients with varus deformities underwent OWHTO and 30 knees of 18 patients underwent UKA surgeries for the treatment of medial compartmental osteoarthritis (OA). The KSS score, FTA, range of motion and complications were evaluated before and after surgery.</p> <p>Results</p> <p>The preoperative mean KSS scores were 49 points in the OWHTO group and 62 in the UKA group which improved postoperatively to 89 (excellent; 19 knees, good; 8 knees), and 88 (excellent; 25, good; 4, fair; 1), respectively. There was no significant difference between the OWHTO and UKA scores. Seventeen patients in the OWHTO group could sit comfortably in the formal Japanese style after surgery. The preoperative mean FTA values for the OWHTO and UKA groups were 182 degrees and 184, and at follow-up measured 169 and 170, respectively. In the UKA group, the femoral component and the polyethylene insertion in one patient was exchanged at 5 years post-surgery and revision TKAs were performed in 2 cases. In the OWHTO group, one tibial plateau fracture and one subcutaneous tissue infection were noted.</p> <p>Conclusions</p> <p>Treatment options should be carefully considered for each OA patient in accordance with their activity levels, grade of advanced OA, age, and range of motion of the knee. OWHTO shows an improved indication for active patients with a good range of motion of the knee.</p

Comparative proteomic analysis of Salmonella enterica serovar Typhimurium ppGpp-deficient mutant to identify a novel virulence protein required for intracellular survival in macrophages

<p>Abstract</p> <p>Background</p> <p>The global ppGpp-mediated stringent response in pathogenic bacteria plays an important role in the pathogenesis of bacterial infections. In <it>Salmonella enterica </it>serovar Typhimurium (<it>S</it>. Typhimurium), several genes, including virulence genes, are regulated by ppGpp when bacteria are under the stringent response. To understand the control of virulence genes by ppGpp in <it>S</it>. Typhimurium, agarose 2-dimensional electrophoresis (2-DE) combined with mass spectrometry was used and a comprehensive 2-DE reference map of amino acid-starved <it>S</it>. Typhimurium strain SH100, a derivative of ATCC 14028, was established.</p> <p>Results</p> <p>Of the 366 examined spots, 269 proteins were successfully identified. The comparative analysis of the wild-type and ppGpp⁰mutant strains revealed 55 proteins, the expression patterns of which were affected by ppGpp. Using a mouse infection model, we further identified a novel virulence-associated factor, STM3169, from the ppGpp-regulated and <it>Salmonella</it>-specific proteins. In addition, <it>Salmonella </it>strains carrying mutations in the gene encoding STM3169 showed growth defects and impaired growth within macrophage-like RAW264.7 cells. Furthermore, we found that expression of <it>stm3169 </it>was controlled by ppGpp and SsrB, a response regulator of the two-component system located on <it>Salmonella </it>pathogenicity island 2.</p> <p>Conclusions</p> <p>A proteomic approach using a 2-DE reference map can prove a powerful tool for analyzing virulence factors and the regulatory network involved in <it>Salmonella </it>pathogenesis. Our results also provide evidence of a global response mediated by ppGpp in <it>S. enterica</it>.</p

Functional Fv fragment of an antibody specific for CD28: Fv-mediated co-stimulation of T cells

AbstractThe most predominant co-stimulation pathway, which is critical for T cell activation and proliferation, is the CD28-B7 pathway. The anti-CD28 monoclonal antibody (mAb) also provides a co-stimulatory signal to T cells. In order to construct a functional Fv fragment (complex of VH and VL domains) of anti-CD28 antibody using a bacterial expression system, cDNA encoding the variable regions of immunoglobulin from 15E8 hybridoma cells was cloned and expressed in Escherichia coli. The Fv fragment was obtained as a soluble protein from the periplasmic fraction and showed a binding pattern similar to parental IgG. The Fv fragment induced proliferation of peripheral blood mononuclear cells in the presence of anti-CD3 or anti-CD2 mAb and enhanced anti-tumor activity of anti-MUC1×anti-CD3 bispecific antibody when tested with lymphokine-activated killer cells with T cell phenotype. Thus, the anti-CD28 Fv fragment will be promising not only for the study of co-stimulation, but also for cancer immunotherapy

Build-up functionalization of anti-EGFR × anti-CD3 bispecific diabodies by integrating high-affinity mutants and functional molecular formats

Designing non-natural antibody formats is a practical method for developing highly functional next-generation antibody drugs, particularly for improving the therapeutic efficacy of cancer treatments. One approach is constructing bispecific antibodies (bsAbs). We previously reported a functional humanized bispecific diabody (bsDb) that targeted epidermal growth factor receptor and CD3 (hEx3-Db). We enhanced its cytotoxicity by constructing an Fc fusion protein and rearranging order of the V domain. In this study, we created an additional functional bsAb, by integrating the molecular formats of bsAb and high-affinity mutants previously isolated by phage display in the form of Fv. Introducing the high-affinity mutations into bsDbs successfully increased their affinities and enhanced their cytotoxicity in vitro and in vivo. However, there were some limitations to affinity maturation of bsDb by integrating high-affinity Fv mutants, particularly in Fc-fused bsDb with intrinsic high affinity, because of their bivalency. The tetramers fractionated from the bsDb mutant exhibited the highest in vitro growth inhibition among the small bsAbs and was comparable to the in vivo anti-tumor effects of Fc-fused bsDbs. This molecule shows cost-efficient bacterial production and high therapeutic potential

ランダム化比較試験によるエドキサバン投与下におけるTKA後DVT発生に対するフットポンプの有効性

長崎大学学位論文 [学位記番号]博（医歯薬）甲第986号 [学位授与年月日]平成29年9月20

A Bacterial Biosensor for Oxidative Stress Using the Constitutively Expressed Redox-Sensitive Protein roGFP2

A highly specific, high throughput-amenable bacterial biosensor for chemically induced cellular oxidation was developed using constitutively expressed redox-sensitive green fluorescent protein roGFP2 in E. coli (E. coli-roGFP2). Disulfide formation between two key cysteine residues of roGFP2 was assessed using a double-wavelength ratiometric approach. This study demonstrates that only a few minutes were required to detect oxidation using E. coli-roGFP2, in contrast to conventional bacterial oxidative stress sensors. Cellular oxidation induced by hydrogen peroxide, menadione, sodium selenite, zinc pyrithione, triphenyltin and naphthalene became detectable after 10 seconds and reached the maxima between 80 to 210 seconds, contrary to Cd2+, Cu2+, Pb2+, Zn2+ and sodium arsenite, which induced the oxidation maximum immediately. The lowest observable effect concentrations (in ppm) were determined as 1.0 × 10−7 (arsenite), 1.0 × 10−4 (naphthalene), 1.0 × 10−4 (Cu2+), 3.8 × 10−4 (H2O2), 1.0 × 10−3 (Cd2+), 1.0 × 10−3 (Zn2+), 1.0 × 10−2 (menadione), 1.0 (triphenyltin), 1.56 (zinc pyrithione), 3.1 (selenite) and 6.3 (Pb2+), respectively. Heavy metal-induced oxidation showed unclear response patterns, whereas concentration-dependent sigmoid curves were observed for other compounds. In vivo GSH content and in vitro roGFP2 oxidation assays together with E. coli-roGFP2 results suggest that roGFP2 is sensitive to redox potential change and thiol modification induced by environmental stressors. Based on redox-sensitive technology, E. coli-roGFP2 provides a fast comprehensive detection system for toxicants that induce cellular oxidation