Intein-mediated backbone cyclization of entolimod confers enhanced radioprotective activity in mouse models

Background Entolimod is a Salmonella enterica flagellin derivate. Previous work has demonstrated that entolimod effectively protects mice and non-human primates from ionizing radiation. However, it caused a “flu-like” syndrome after radioprotective and anticancer clinical application, indicating some type of immunogenicity and toxicity. Cyclization is commonly used to improve the in vivo stability and activity of peptides and proteins. Methods We designed and constructed cyclic entolimod using split Nostoc punctiforme DnaE intein with almost 100% cyclization efficiency. We adopted different strategies to purify the linear and circular entolimod due to their different topologies. Both of linear and circular entolimod were first purified by Ni-chelating affinity chromatography, and then the linear and circular entolimod were purified by size-exclusion and ion-exchange chromatography, respectively. Results The circular entolimod showed significantly increased both the in vitro NF-κB signaling and in vivo radioprotective activity in mice. Conclusion Our data indicates that circular entolimod might be a good candidate for further clinical investigation

A Review of Fibre Reinforced Polymer (FRP) Reinforced Concrete Composite Column Members Modelling and Analysis Techniques

The use of fibre-reinforced polymer (FRP) to confine concrete columns improves the strength and ductility of the columns by reducing passive lateral confinement pressure. Many numerical and analytical formulations have been proposed in the literature to describe the compressive behaviour of FRP confined concrete under both monotonic and cyclic loads. However, the effect of a stress/strain level in the columns has not been well defined because of the lack of well-defined strategies of modelling and oversimplification of the model. This paper reviews the existing FRP combinations and the available numerical and analytical methods to determine the effectiveness of the adopted method. An effort has been made to examine the usage of FRP materials in column applications in existing building regimes and highlights the possible future scopes to improve the use of FRP confined concrete in civil applications

Tubeimoside-1 up-regulates p21 expression and induces apoptosis and G2/M phase cell cycle arrest in human bladder cancer T24 cells

Tubeimoside-1 (TBMS1) is a triterpenoid saponin with potent anticancer properties. In this study, for the first, we examined the anti-proliferative effects of TBMS1 in human bladder cancer T24 cells and its ability to induce apoptosis and cell cycle arrest. Our results demonstrated that TBMS1 decreased the cell viability of bladder cancer T24 cells in a dose-dependent manner. Flow cytometric analysis showed that TBMS1 significantly triggered apoptosis in T24 cells and arrested cell cycle at G2/M phase in a dose-dependent manner. Further characterization demonstrated that TBMS1-induced apoptosis is associated with dissipation in mitochondrial membrane potential (??m), down-regulation of Bcl-2, and up-regulation of Bax and p21 in TBMS1-treated T24 cells. These in vitro results suggested that TBMS1 is an effective anti-bladder cancer natural compound that worth further mechanistic and therapeutic studies in human bladder cancer

Unveiling the Stable Nature of the Solid Electrolyte Interphase between Lithium Metal and LiPON via Cryogenic Electron Microscopy

The solid electrolyte interphase (SEI) is regarded as the most complex but the least understood constituent in secondary batteries using liquid and solid electrolytes. The nanostructures of SEIs were recently reported to be equally important to the chemistry of SEIs for stabilizing Li metal in liquid electrolyte. However, the dearth of such knowledge in all-solid-state battery (ASSB) has hindered a complete understanding of how certain solid-state electrolytes, such as LiPON, manifest exemplary stability against Li metal. Characterizing such solid-solid interfaces is difficult due to the buried, highly reactive, and beam-sensitive nature of the constituents within. By employing cryogenic electron microscopy (cryo-EM), the interphase between Li metal and LiPON is successfully preserved and probed, revealing a multilayer mosaic SEI structure with concentration gradients of nitrogen and phosphorous, materializing as crystallites within an amorphous matrix. This unique SEI nanostructure is less than 80 nm and is shown stable and free of any organic lithium containing species or lithium fluoride components, in contrast to SEIs often found in state-of-the-art organic liquid electrolytes. Our findings reveal insights on the nanostructures and chemistry of such SEIs as a key component in lithium metal batteries to stabilize Li metal anode

Hyperoxemia and excess oxygen use in early acute respiratory distress syndrome : Insights from the LUNG SAFE study

Publisher Copyright: © 2020 The Author(s). Copyright: Copyright 2020 Elsevier B.V., All rights reserved.Background: Concerns exist regarding the prevalence and impact of unnecessary oxygen use in patients with acute respiratory distress syndrome (ARDS). We examined this issue in patients with ARDS enrolled in the Large observational study to UNderstand the Global impact of Severe Acute respiratory FailurE (LUNG SAFE) study. Methods: In this secondary analysis of the LUNG SAFE study, we wished to determine the prevalence and the outcomes associated with hyperoxemia on day 1, sustained hyperoxemia, and excessive oxygen use in patients with early ARDS. Patients who fulfilled criteria of ARDS on day 1 and day 2 of acute hypoxemic respiratory failure were categorized based on the presence of hyperoxemia (PaO2 > 100 mmHg) on day 1, sustained (i.e., present on day 1 and day 2) hyperoxemia, or excessive oxygen use (FIO2 ≥ 0.60 during hyperoxemia). Results: Of 2005 patients that met the inclusion criteria, 131 (6.5%) were hypoxemic (PaO2 < 55 mmHg), 607 (30%) had hyperoxemia on day 1, and 250 (12%) had sustained hyperoxemia. Excess FIO2 use occurred in 400 (66%) out of 607 patients with hyperoxemia. Excess FIO2 use decreased from day 1 to day 2 of ARDS, with most hyperoxemic patients on day 2 receiving relatively low FIO2. Multivariate analyses found no independent relationship between day 1 hyperoxemia, sustained hyperoxemia, or excess FIO2 use and adverse clinical outcomes. Mortality was 42% in patients with excess FIO2 use, compared to 39% in a propensity-matched sample of normoxemic (PaO2 55-100 mmHg) patients (P = 0.47). Conclusions: Hyperoxemia and excess oxygen use are both prevalent in early ARDS but are most often non-sustained. No relationship was found between hyperoxemia or excessive oxygen use and patient outcome in this cohort. Trial registration: LUNG-SAFE is registered with ClinicalTrials.gov, NCT02010073publishersversionPeer reviewe

Automatic Methods to Enhance Server Systems in Access Control Diagnosis

Access control configurations are gatekeepers to block unwelcome access to sensitive data. Unfortunately, system administrators (sysadmins) sometimes over-grant permissions when they resolve unintended access-deny issues reported by legitimate users. The mistakes in the access control configurations can result in severe consequences, such as data breaches and system compromises. To make things worse, the access control misconfigurations may stay silent until the security incident happens. This dissertation explores two approaches to help sysadmins diagnose the access-deny issues and reduce the permission over-granting mistakes. The first approach takes the problem of insufficient access-control logging in server applications. We designed an automated tool, SecLog, to automatically add missing access-deny log messages, and also enhance existing ones with relevant information to guide sysadmins to diagnose the access-deny issues. The second approach tackles the problem of blind spots in knowledge and system settings for sysadmins in solving access-deny issues. We propose a system, Multiview, to automatically mutate the system configurations to explore possible directions and let each direction grant as few permissions as possible. Multiview provides a detailed diagnosis report, including access-control configurations that are related to the denial, possible directions to allow the request, as well as the impact of each direction on the access-control state of the entire system to assist sysadmins during diagnosis

Fractional boundary layer flow and radiation heat transfer of MHD viscoelastic fluid over an unsteady stretching surface

This paper presents an investigation for magnetohydrodynamic (MHD) viscoelastic fluid boundary layer flow and radiation heat transfer over an unsteady stretching sheet in presence of heat source. Time dependent fractional derivative is first introduced in formulating the boundary layer equations. Numerical solutions are obtained by using the finite difference scheme and L1-algorithm approximation. Results indicate that the proposed model describes a basic delaying times framework for viscoelastic flow and radiation heat transfer. The effects of involved parameters on velocity and temperature fields are shown graphically and analyzed in detail

Bioconvection heat transfer of a nanofluid over a stretching sheet with velocity slip and temperature jump

This paper presents an investigation for bioconvection heat transfer of a nanofluid containing gyrotactic microorganisms over a stretching sheet, in which the effects of radiation, velocity slip, and temperature jump are taken into account. The non-linear governing equations are reduced into four ordinary differential equations by similarity transformations and solved by homotopy analysis method, which is verified with numerical results in good agree. Results indicate that the density of motile microorganisms and gyrotactic microorganisms increase with bioconvection Rayleigh number, while decrease with increasing in bioconvection Peclet number and bioconvection Lewis number. It is also found that the Nusselt number, Sherwood number, and gyrotactic microorganisms density depend strongly on the buoyancy, nanofluids, and bioconvection parameters