Three dimensional elasticity solutions of sandwich panels using the extended Kantorovich method

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Fatigue due to vortex induced cross-flow oscillations in free spanning pipelines supported on elastic soil bed

An analytical solution is presented for fatigue response due to crossflow vibration of free spanning submarine pipelines supported on semi-infinite elastic soil bed at the ends. The formulation includes the second order bending effect of axial force present in the pipeline. Free vibration response parameters are obtained by solving the governing differential equations and satisfying the appropriate boundary conditions for both symmetric and anti-symmetric modes.These parameters are used for assessing the fatigue damage due to crossflow vortex induced vibration under wave and current action as per new draft guidelines of DNV. Results are presented illustrating the effect of axial force and soil stiffness on the fatigue life of a free span under a combined wave and current loading scenario. The maximum permissible spans obtained from the full fatigue analysis are compared with those obtained from onset of cross-flow vibration criteria

In-service buckling of submarine pipelines with an arbitrary initial out-of-straightness

An analytical solution has been presented for the vertical buckling of submarine pipelines laid on seabed with initial stress-free geometric out-of-straightness of arbitrary shape. The arbitrary imperfectionshape as well as the deflection in the buckled portion is expressed in terms of Fourier series. The coefficients of the Fourier terms for the deflection under the action of axial force and submerged weight are obtained through energy principles. The relation between the compressive forces in the buckled portion and far away from it are obtained using both constant and deformation dependent friction models for axial friction at the pipeline-seabed interface. The obtained series solution is found to yield the same results as the classical exact solution of governing differential equations for a perfect (zero imperfection) pipeline. Numerical results are presented to illustrate the effects of the magnitude and the shape of initial imperfections on the instability temperature and the post buckling equilibrium path of imperfect pipelines. The maximum deflections and the stresses associated with the post-buckling states are also determined. The effects of the nature and the magnitude of axial friction on the buckling characteristics are investigated

Unified Geometrically Nonlinear Formulation of All Higher-order Shear Deformation Theories for Cross-ply Plates

Several higher-order shear deformation theories have been proposed for laminated plates, based on the expansions of displacements across the thickness, which are the same for all layers. In this study, a unified formulation of all higher-order theories is presented for cross-ply laminated plates based on polynomial expansions of displacements in the thickness coordinate z. It includes all the models available in literature. The governing equations for linear static and free vibfation response, and for buckling under inplane load are derived. The expressions for the stiffness matrix, inertia matrix, geometric stiffness matrix, and the load vector are developed for a simply supported rectangular plate using Navier's solution. A general purpose, single programme has been developed for all higher-order laminated plate theories

Proteolysis of HCF-1 by Ser/Thr glycosylation-incompetent O-GlcNAc transferase:UDP-GlcNAc complexes

In complex with the cosubstrate UDP-N-acetylglucosamine (UDP-GlcNAc),O-linked-GlcNAc transferase (OGT) catalyzes Ser/ThrO-GlcNAcylation of many cellular proteins and proteolysis of the transcriptional coregulator HCF-1. Such a dual glycosyltransferase-protease activity, which occurs in the same active site, is unprecedented and integrates both reversible and irreversible forms of protein post-translational modification within one enzyme. Although occurring within the same active site, we show here that glycosylation and proteolysis occur through separable mechanisms. OGT consists of tetratricopeptide repeat (TPR) and catalytic domains, which, together with UDP-GlcNAc, are required for both glycosylation and proteolysis. Nevertheless, a specific TPR domain contact with the HCF-1 substrate is critical for proteolysis but not Ser/Thr glycosylation. In contrast, key catalytic domain residues and even a UDP-GlcNAc oxygen important for Ser/Thr glycosylation are irrelevant for proteolysis. Thus, from a dual glycosyltransferase-protease, essentially single-activity enzymes can be engineered both in vitro and in vivo. Curiously, whereas OGT-mediated HCF-1 proteolysis is limited to vertebrate species, invertebrate OGTs can cleave human HCF-1. We present a model for the evolution of HCF-1 proteolysis by OGT

The conserved threonine-rich region of the HCF-1PRO repeat activates promiscuous OGT:UDP-GlcNAc glycosylation and proteolysis activities

O-Linked GlcNAc transferase (OGT) possesses dual glycosyltransferase-protease activities. OGT thereby stably glycosylates serines and threonines of numerous proteins and, via a transient glutamate glycosylation, cleaves a single known substrate-the so-called HCF-1 <sub>PRO</sub> repeat of the transcriptional co-regulator host-cell factor 1 (HCF-1). Here, we probed the relationship between these distinct glycosylation and proteolytic activities. For proteolysis, the HCF-1 <sub>PRO</sub> repeat possesses an important extended threonine-rich region that is tightly bound by the OGT tetratricopeptide-repeat (TPR) region. We report that linkage of this HCF-1 <sub>PRO</sub> -repeat, threonine-rich region to heterologous substrate sequences also potentiates robust serine glycosylation with the otherwise poor R <sub>p</sub> -αS-UDP-GlcNAc diastereomer phosphorothioate and UDP-5S-GlcNAc OGT co-substrates. Furthermore, it potentiated proteolysis of a non-HCF-1 <sub>PRO</sub> -repeat cleavage sequence, provided it contained an appropriately positioned glutamate residue. Using serine- or glutamate-containing HCF-1 <sub>PRO</sub> -repeat sequences, we show that proposed OGT-based or UDP-GlcNAc-based serine-acceptor residue activation mechanisms can be circumvented independently, but not when disrupted together. In contrast, disruption of both proposed activation mechanisms even in combination did not inhibit OGT-mediated proteolysis. These results reveal a multiplicity of OGT glycosylation strategies, some leading to proteolysis, which could be targets of alternative molecular regulatory strategies

COVID-19 alcoholic cirrhosis and non-alcoholic steatohepatitis cirrhosis outcomes among hospitalized patients in the United States: Insight from National Inpatient Sample database

Patients with co-morbidities like cirrhosis are at risk of worse outcome from COVID-19 infection. Given limited prior studies, we evaluated outcomes associated with COVID-19 infection in alcoholic and non-alcoholic steatohepatitis cirrhotic (CC+) versus cirrhotic without COVID-19 (CC-). We performed retrospective analysis of 822,604 patients including 28,610 COVID-19 patients from the National Inpatient Sample database with alcoholic and NASH cirrhosis enrolled between 1 January 2020 to 31 December 2020, with univariate and multivariate regression analyses. Primary outcome was mortality and secondary outcomes was mechanical ventilation, vasopressor use, length of stay, hospitalization expense and predictors of mortality. In-hospital mortality was three time higher in the CC+ group compared to those in the CC- group(18.6% vs. 5.96%

Static and vibration analysis of functionally graded beams using refined shear deformation theory

Static and vibration analysis of functionally graded beams using refined shear deformation theory is presented. The developed theory, which does not require shear correction factor, accounts for shear deformation effect and coupling coming from the material anisotropy. Governing equations of motion are derived from the Hamilton's principle. The resulting coupling is referred to as triply coupled axial-flexural response. A two-noded Hermite-cubic element with five degree-of-freedom per node is developed to solve the problem. Numerical results are obtained for functionally graded beams with simply-supported, cantilever-free and clamped-clamped boundary conditions to investigate effects of the power-law exponent and modulus ratio on the displacements, natural frequencies and corresponding mode shapes