Damage localization of closing cracks using a signal decomposition technique

Fatigue cracks are a common occurrence in engineering structures subjected to dynamic loading and need to identify at its earliest stage before it leads to catastrophic failure. The presence of fatigue-breathing crack or closing cracks is usually characterised by the presence of sub, super-harmonics, and inter-modulation in the response of the structure subjected to harmonic excitation. It should be mentioned here that the amplitude of nonlinear harmonics are of very less order in magnitude when compared to linear or excitation component. Further, these nonlinear components often get buried in noise as both are having matched (low) energy levels. The present work attempts to decompose the acceleration time history response using singular spectrum analysis and propose a strategy to extract the nonlinear components from the residual noisy time history component. A new damage index based on these extracted nonlinear features is also proposed for closing crack localization. The effectiveness of the proposed closing crack localization approach is illustrated using detailed numerical studies and validated with lab level experimentation on the simple beam-like structure. It can be concluded from the investigations that the proposed signal decomposition based damage localization technique can detect and locate more than one crack present in the structure

SAFER geodatabase for the Kathmandu Valley: Geotechnical and geological variability

The Kathmandu Valley is within a seismically active region with only few recorded strong-motion data. Geophysical information in the Valley is also sparse. In addition, the absence of an open database which compiles in situ geophysical tests, borehole records, and geotechnical laboratory data is affecting the advancement of knowledge in the region. This article presents SAFER/GEO-591 database, named after the Engineering and Physical Science Research Council (EPSRC)-funded project Seismic Safety and Resilience of Schools in Nepal (SAFER). SAFER/GEO-591 contains data from groundwater wells and boreholes originally commissioned for research and commercial purposes. This work describes (1) the quality assessment and harmonization process conducted on the dataset, (2) the variation of shear-wave velocity (V_S) measurements and geotechnical parameters with depth and elevation in the Valley, (3) the current understanding of the Valley sediment/bedrock topography, and finally (4) new geological cross sections. A companion article presents an updated V_(S30) map across the Valley based on the contributions of this article. The database can be downloaded from the University of Bristol repository via DOI: https://doi.org/10.5523/bris.3gjcvx51lnpuv269xsa1yrb0rw

The SAFER Geodatabase for the Kathmandu Valley:geotechnical and geological variability

The Kathmandu Valley is within a seismically active region with only few recorded strong-motion data. Geophysical information in the Valley is also sparse. In addition, the absence of an open database which compiles in situ geophysical tests, borehole records, and geotechnical laboratory data is affecting the advancement of knowledge in the region. This article presents SAFER/GEO-591 database, named after the Engineering and Physical Science Research Council (EPSRC)-funded project Seismic Safety and Resilience of Schools in Nepal (SAFER). SAFER/GEO-591 contains data from groundwater wells and boreholes originally commissioned for research and commercial purposes. This work describes (1) the quality assessment and harmonization process conducted on the dataset, (2) the variation of shear-wave velocity (V_S) measurements and geotechnical parameters with depth and elevation in the Valley, (3) the current understanding of the Valley sediment/bedrock topography, and finally (4) new geological cross sections. A companion article presents an updated V_(S30) map across the Valley based on the contributions of this article. The database can be downloaded from the University of Bristol repository via DOI: https://doi.org/10.5523/bris.3gjcvx51lnpuv269xsa1yrb0rw

Co-Depletion of Cathepsin B and uPAR Induces G0/G1 Arrest in Glioma via FOXO3a Mediated p27Kip1 Upregulation

Cathepsin B and urokinase plasminogen activator receptor (uPAR) are both known to be overexpressed in gliomas. Our previous work and that of others strongly suggest a relationship between the infiltrative phenotype of glioma and the expression of cathepsin B and uPAR. Though their role in migration and adhesion are well studied the effect of these molecules on cell cycle progression has not been thoroughly examined.Cathepsin B and uPAR single and bicistronic siRNA plasmids were used to downregulate these molecules in SNB19 and U251 glioma cells. FACS analysis and BrdU incorporation assay demonstrated G0/G1 arrest and decreased proliferation with the treatments, respectively. Immunoblot and immunocyto analysis demonstrated increased expression of p27(Kip1) and its nuclear localization with the knockdown of cathepsin B and uPAR. These effects could be mediated by alphaVbeta3/PI3K/AKT/FOXO pathway as observed by the decreased alphaVbeta3 expression, PI3K and AKT phosphorylation accompanied by elevated FOXO3a levels. These results were further confirmed with the increased expression of p27(Kip1) and FOXO3a when treated with Ly294002 (10 microM) and increased luciferase expression with the siRNA and Ly294002 treatments when the FOXO binding promoter region of p27(Kip1) was used. Our treatment also reduced the expression of cyclin D1, cyclin D2, p-Rb and cyclin E while the expression of Cdk2 was unaffected. Of note, the Cdk2-cyclin E complex formation was reduced significantly.Our study indicates that cathepsin B and uPAR knockdown induces G0/G1 arrest by modulating the PI3K/AKT signaling pathway and further increases expression of p27(Kip1) accompanied by the binding of FOXO3a to its promoter. Taken together, our findings provide molecular mechanism for the G0/G1 arrest induced by the downregulation of cathepsin B and uPAR in SNB19 and U251 glioma cells

Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.

Studies of η\eta and η′\eta' production in pppp and ppPb collisions

The production of $\eta$ and $\eta'$ mesons is studied in proton-proton and proton-lead collisions collected with the LHCb detector. Proton-proton collisions are studied at center-of-mass energies of $5.02$ and $13~{\rm TeV}$, and proton-lead collisions are studied at a center-of-mass energy per nucleon of $8.16~{\rm TeV}$. The studies are performed in center-of-mass rapidity regions $2.5<y_{\rm c.m.}<3.5$ (forward rapidity) and $-4.0<y_{\rm c.m.}<-3.0$ (backward rapidity) defined relative to the proton beam direction. The $\eta$ and $\eta'$ production cross sections are measured differentially as a function of transverse momentum for $1.5<p_{\rm T}<10~{\rm GeV}$ and $3<p_{\rm T}<10~{\rm GeV}$, respectively. The differential cross sections are used to calculate nuclear modification factors. The nuclear modification factors for $\eta$ and $\eta'$ mesons agree at both forward and backward rapidity, showing no significant evidence of mass dependence. The differential cross sections of $\eta$ mesons are also used to calculate $\eta/\pi^0$ cross section ratios, which show evidence of a deviation from the world average. These studies offer new constraints on mass-dependent nuclear effects in heavy-ion collisions, as well as $\eta$ and $\eta'$ meson fragmentation.Comment: All figures and tables, along with machine-readable versions and any supplementary material and additional information, are available at https://lhcbproject.web.cern.ch/Publications/p/LHCb-PAPER-2023-030.html (LHCb public pages

Observation of Cabibbo-suppressed two-body hadronic decays and precision mass measurement of the Ωc0\Omega_{c}^{0} baryon

The first observation of the singly Cabibbo-suppressed $\Omega_{c}^{0}\to\Omega^{-}K^{+}$ and $\Omega_{c}^{0}\to\Xi^{-}\pi^{+}$ decays is reported, using proton-proton collision data at a centre-of-mass energy of $13\,{\rm TeV}$, corresponding to an integrated luminosity of $5.4\,{\rm fb}^{-1}$, collected with the LHCb detector between 2016 and 2018. The branching fraction ratios are measured to be $\frac{\mathcal{B}(\Omega_{c}^{0}\to\Omega^{-}K^{+})}{\mathcal{B}(\Omega_{c}^{0}\to\Omega^{-}\pi^{+})}=0.0608\pm0.0051({\rm stat})\pm 0.0040({\rm syst})$, $\frac{\mathcal{B}(\Omega_{c}^{0}\to\Xi^{-}\pi^{+})}{\mathcal{B}(\Omega_{c}^{0}\to\Omega^{-}\pi^{+})}=0.1581\pm0.0087({\rm stat})\pm0.0043({\rm syst})\pm0.0016({\rm ext})$. In addition, using the $\Omega_{c}^{0}\to\Omega^{-}\pi^{+}$ decay channel, the $\Omega_{c}^{0}$ baryon mass is measured to be $M(\Omega_{c}^{0})=2695.28\pm0.07({\rm stat})\pm0.27({\rm syst})\pm0.30({\rm ext})\,{\rm MeV}/c^{2}$, improving the precision of the previous world average by a factor of four.Comment: All figures and tables, along with any supplementary material and additional information, are available at https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2023-011.html (LHCb public pages