1,918 research outputs found

    Cyclic testing of reinforced concrete columns with double or one-side headed shear reinforcement

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    The effectiveness of single-leg crossties that were anchored by heads in reinforced concrete columns was assessed. Seven reinforced concrete columns were tested under reversed cyclic loading with a 10Ā % axial load of the nominal axial capacity of the columns. Four columns were designed to fail in a flexural mode, and three columns were designed to fail in a shear mode. The main variable was the anchorage type of crossties: conventional crossties that were anchored with 135Ā° and 90Ā° hooks, crossties that were anchored with one-side head and one-side 180Ā° hook, and crossties that were anchored with double heads. The test results indicate that the hysteretic behavior of the columns with crossties that were anchored by double heads or one-side head was similar or superior to the columns with conventional crossties anchored by hooks in terms of ductility and energy dissipation. After the cover concrete spalled, the 90Ā° hooks inevitably opened and the column longitudinal bars buckled. However, the heads could delay the buckling of the column bars and the columns could maintain their capacities until 8Ā % drift ratio for the columns that were designed to fail in a flexural mode. For the columns that were designed to fail in a shear mode, all columns showed similar behaviors and had identical strengths. The columns with the headed crossties had smaller crack widths than the columns with conventional crossties because the headed crossties well confined the core concrete under severe shear deformation. The test results show that headed crossties can effectively confine the column bars and core concrete of the columns: therefore, the ductility and energy dissipation capacity of the columns were improved

    Characterization of DNA-binding activity of ZĪ± domains from poxviruses and the importance of the Ī²-wing regions in converting B-DNA to Z-DNA

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    The E3L gene is essential for pathogenesis in vaccinia virus. The E3L gene product consists of an N-terminal ZĪ± domain and a C-terminal double-stranded RNA (dsRNA) binding domain; the left-handed Z-DNA-binding activity of the ZĪ± domain of E3L is required for viral pathogenicity in mice. E3L is highly conserved among poxviruses, including the smallpox virus, and it is likely that the orthologous ZĪ± domains play similar roles. To better understand the biological function of E3L proteins, we have investigated the Z-DNA-binding behavior of five representative ZĪ± domains from poxviruses. Using surface plasmon resonance (SPR), we have demonstrated that these viral ZĪ± domains bind Z-DNA tightly. Ability of ZĪ±[subscript E3L] converting B-DNA to Z-DNA was measured by circular dichroism (CD). The extents to which these ZĪ±s can stabilize Z-DNA vary considerably. Mutational studies demonstrate that residues in the loop of the Ī²-wing play an important role in this stabilization. Notably the ZĪ± domain of vaccinia E3L acquires ability to convert B-DNA to Z-DNA by mutating amino acid residues in this region. Differences in the host cells of the various poxviruses may require different abilities to stabilize Z-DNA; this may be reflected in the observed differences in behavior in these ZĪ± proteins.Korean Science and Engineering Foundation (National Research Laboratory Program (NRL-2006-02287))Korean Science and Engineering Foundation (Ubiquitome Research Program (M10533010002-06N3301-00210))Korean Science and Engineering Foundation (21C Frontier Functional Proteomics Program (FPR06B2-120))National Institutes of Health (U.S.)Ellison Medical FoundationKorea (South). Ministry of Science and Technology (National Laboratory program (NRL-2006-02287)

    Hepatitis C Virus Core Protein Inhibits Interleukin 12 and Nitric Oxide Production from Activated Macrophages

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    AbstractA characteristic feature of hepatitis C virus (HCV) infection is a high frequency of persistence and the progression to chronic liver diseases. Recent data suggest that prevalent T helper (Th) 2 immunity as well as weak HCV-specific T-cell response is associated with viral persistence. Here, we showed that the production of interleukin 12 (IL-12) and nitric oxide (NO) that is critical for the induction of Th1 and innate immunity, but not that of tumor necrosis factor Ī± (TNF-Ī±), was significantly suppressed in both HCV core-expressing macrophage cell lines and mouse peritoneal macrophages treated with recombinant core protein. In addition, IL-12 p40 promoter activity was repressed by the presence of HCV core in macrophages stimulated with lipopolysaccharride (LPS) following IFN-Ī³ treatment, indicating that IL-12 production may be downregulated at the transcriptional level. We also found that proliferation of T cells and IFN-Ī³ production in mixed lymphocyte reactions (MLR) with core-expressing cells were inhibited. Taken together, our results suggest that HCV core protein could play roles in suppressing the induction of Th1 immunity through inhibition of IL-12 and NO production

    Primary Diffuse Leptomeningeal Gliomatosis: Report of a Case Presenting with Chronic Meningitis

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    Neoplastic meningitis occurs in approximately 5% of patients with cancer. Primary diffuse leptomeningeal gliomatosis is a rare condition whereby a glioma arises from heterotopic cell nests in the leptomeninges. We report here a case presenting with clinical features similar to those of chronic infectious meningitis without positive cerebrospinal fluid cytology. Neurological signs in our patient deteriorated progressively without responding to antitubercular, antiviral, or antibiotic therapy. Leptomeningeal biopsy sampling revealed the condition to be primary diffuse leptomeningeal gliomatosis

    Analysis of different tumor volume thresholds of insignificant prostate cancer and their implications for active surveillance patient selection and monitoring

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    PurposeWe compared oncological outcomes according to tumor volume (TV) thresholds defining both classical and updated insignificant prostate cancer (IPC), since the TV threshold can be used as clinical parameter for active surveillance.MethodsBetween 2001 and 2012, we retrospectively analyzed 331 organ-confined prostate cancer patients who had preoperative Gleason score 6, preoperative PSA under 10 ng/mL and pathologic TV less than 1.3 mL. Among them, 81 of 331 (24.5%) had Gleason grade 4/5 disease postoperatively. Patients were stratified into two groups: (1) TV less than 0.5 mL, using the classical definition; and (2) TV between 0.5 mL and 1.3 mL, using the range of updated definition. We compared biochemical recurrence (BCR)-free survival and identified independent predictors of BCR in each group.ResultsGroup 2 had more Gleason grade 4/5 disease than group 1 (P<0.001). On multivariate analysis, Gleason grade 4/5 disease was not associated with BCR in group 1 (P=0.132). However, it was an independent predictor for BCR in group 2 (P=0.042). BCR-free survival were not significantly different according to the presence of Gleason grade 4/5 disease in group 1 (P=0.115). However, in group 2, it was significantly different according to the presence of Gleason grade 4/5 disease (P=0.041).ConclusionsAlthough the TV thresholds of the two definitions of IPC vary only slightly, this difference was enough to result in different clinical course if Gleason grade 4/5 disease was present. Therefore, the updated IPC TV threshold should be carefully applied as clinical parameter for active surveillance

    Crystallization and preliminary X-ray analysis of neoagarobiose hydrolase from Saccharophagus degradans 2-40

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    Many agarolytic bacteria degrade agar polysaccharide into the disaccharide unit neoagarobiose [O-3,6-anhydro-Ī±-L-galactopyranosyl-(1ā†’3)-D-galactose] using various Ī²-agarases. Neoagarobiose hydrolase is an enzyme that acts on the Ī±-1,3 linkage in neoagarobiose to yield D-galactose and 3,6-anhydro-L-galactose. This activity is essential in both the metabolism of agar by agarolytic bacteria and the production of fermentable sugars from agar biomass for bioenergy production. Neoagarobiose hydrolase from the marine bacterium Saccharophagus degradans 2-40 was overexpressed in Escherichia coli and crystallized in the monoclinic space group C2, with unit-cell parameters a = 129.83, b = 76.81, c = 90.11 ƅ, Ī² = 101.86Ā°. The crystals diffracted to 1.98 ƅ resolution and possibly contains two molecules in the asymmetric unit

    Proximity-Directed Labeling Reveals a New Rapamycin-Induced Heterodimer of FKBP25 and FRB in Live Cells

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    Mammalian target of rapamycin (mTOR) signaling is a core pathway in cellular metabolism, and control of the mTOR pathway by rapamycin shows potential for the treatment of metabolic diseases. In this study, we employed a new proximity biotin-labeling method using promiscuous biotin ligase (pBirA) to identify unknown elements in the rapamycin-induced interactome on the FK506-rapamycin binding (FRB) domain in living cells. FKBP25 showed the strongest biotin labeling by FRB-pBirA in the presence of rapamycin. Immunoprecipitation and immunofluorescence experiments confirmed that endogenous FKBP25 has a rapamycin-induced physical interaction with the FRB domain. Furthermore, the crystal structure of the ternary complex of FRB-rapamycin-FKBP25 was determined at 1.67-angstrom resolution. In this crystal structure we found that the conformational changes of FRB generate a hole where there is a methionine-rich space, and covalent metalloid coordination was observed at C2085 of FRB located at the bottom of the hole. Our results imply that FKBP25 might have a unique physiological role related to metallomics in mTOR signaling.ope
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