An Elasto-plastic Model for Liquefiable Sands Subjected to Torsional Shear Loadings

This paper presents a modeling procedure for simulating the monotonic undrained torsional shear behavior of sands, including stress-strain relationship, and excess pore water pressure generation, while considering the void ratio and stress level dependence of stress-strain-dilatancy behavior of sand. A unique set of soil parameters is required by the model to satisfactorily predict the undrained behavior of loose and dense Toyoura sand over a wide range of initial void ratios and confining pressures, as proven by simulating experimental data produced by the authors and found in the literature

Anti-inflammatory and anti-oxidant properties of Ipomoea nil (Linn.) Roth significantly alleviates cigarette smoke (CS)-induced acute lung injury via possibly inhibiting the NF-κB pathway

Acute respiratory distress syndrome (ARDS), a serious manifestation of acute lung injury (ALI), is a debilitating inflammatory lung disease that is caused by multiple risk factors. One of the primary causes that can lead to ALI/ARDS is cigarette smoke (CS) and its primary mode of action is via oxidative stress. Despite extensive research, no appropriate therapy is currently available to treat ALI/ARDS, which means there is a dire need for new potential approaches. In our study we explored the protective effects of 70 % methanolic-aqueous extract of Ipomoea nil (Linn.) Roth, named as In.Mcx against CS-induced ALI mice models and RAW 264.7 macrophages because Ipomoea nil has traditionally been used to treat breathing irregularities. Male Swiss albino mice (20–25 ± 2 g) were subjected to CS for 10 uninterrupted days in order to establish CS-induced ALI murine models. Dexamethasone (1 mg/kg), In.Mcx (100 200, and 300 mg/kg) and normal saline (10 mL/kg) were given to respective animal groups, 1 h before CS-exposure. 24 h after the last CS exposure, the lungs and bronchoalveolar lavage fluid (BALF) of all euthanized mice were harvested. Altered alveolar integrity and elevated lung weight-coefficient, total inflammatory cells, oxidative stress, expression of pro-inflammatory cytokines (IL-1β and IL-6) and chemokines (KC) were significantly decreased by In.Mcx in CS-exposed mice. In.Mcx also revealed significant lowering IL-1β, IL-6 and KC expression in CSE (4 %)-activated RAW 264.7 macrophage. Additionally, In.Mcx showed marked enzyme inhibition activity against Acetylcholinesterase, Butyrylcholinesterase and Lipoxygenase. Importantly, In.Mcx dose-dependently and remarkably suppressed the CS-induced oxidative stress via not only reducing the MPO, TOS and MDA content but also improving TAC production in the lungs. Accordingly, HPLC analysis revealed the presence of many important antioxidant components. Finally, In.Mcx showed a marked decrease in the NF-κB expression both in in vivo and in vitro models. Our findings suggest that In.Mcx has positive therapeutic effects against CS-induced ALI via suppressing uncontrolled inflammatory response, oxidative stress, lipoxygenase and NF-κB p65 pathway

Assessment and improvement of the Plasmodium yoelii yoelii genome annotation through comparative analysis

Motivation: The sequencing of the Plasmodium yoelii genome, a model rodent malaria parasite, has greatly facilitated research for the development of new drug and vaccine candidates against malaria. Unfortunately, only preliminary gene models were annotated on the partially sequenced genome, mostly by in silico gene prediction, and there has been no major improvement of the annotation since 2002

Identification of β-Lactams Active against Mycobacterium tuberculosis by a Consortium of Pharmaceutical Companies and Academic Institutions

Rising antimicrobial resistance challenges our ability to combat bacterial infections. The problem is acute for tuberculosis (TB), the leading cause of death from infection before COVID-19. Here, we developed a framework for multiple pharmaceutical companies to share proprietary information and compounds with multiple laboratories in the academic and government sectors for a broad examination of the ability of β-lactams to kill Mycobacterium tuberculosis (Mtb). In the TB Drug Accelerator (TBDA), a consortium organized by the Bill & Melinda Gates Foundation, individual pharmaceutical companies collaborate with academic screening laboratories. We developed a higher order consortium within the TBDA in which four pharmaceutical companies (GlaxoSmithKline, Sanofi, MSD, and Lilly) collectively collaborated with screeners at Weill Cornell Medicine, the Infectious Disease Research Institute (IDRI), and the National Institute of Allergy and Infectious Diseases (NIAID), pharmacologists at Rutgers University, and medicinal chemists at the University of North Carolina to screen ∼8900 β-lactams, predominantly cephalosporins, and characterize active compounds. In a striking contrast to historical expectation, 18% of β-lactams screened were active against Mtb, many without a β-lactamase inhibitor. One potent cephaloporin was active in Mtb-infected mice. The steps outlined here can serve as a blueprint for multiparty, intra- and intersector collaboration in the development of anti-infective agents

Centrifuge modeling of earth-reinforced retaining walls

This paper is on the centrifuge modeling of reinforced soil retaining walls with modular blocks facing. The influence of design parameters, such as length and vertical spacing of reinforcement, on the behaviour of the structure was investigated. A total of 11 models were tested, each one with different length of reinforcement or spacing. Each model was constructed and then placed in the centrifuge in order to increase gravitational acceleration up to 35 g, reproducing the soil behaviour of a 5-m high wall. Vertical and horizontal displacements were recorded by means of a laser profiler which enabled tracking of deformations in the structure along its longitudinal cross section, essentially drawing its deformed shape. As expected, the results confirmed reinforcement parameters to be the governing factor in the behaviour of reinforced soil structures since increasing length and reducing spacing improved structural stability. However, the influence of the length was found to be the leading factor that reduced facial deformations up to five times, and the spacing playing an important role especially in unstable configurations. The failure surface was characterised by the same shape (circular) and depth, regardless of the reinforcement configuration. Furthermore, the results confirmed the over- conservatism of design codes, since models with reinforcement layers 0.3H long showed almost negligible deformations. The test results may be used to set up further numerical modeling in order to investigate on other issues, such as the influence of the reinforcement stiffness and varying backfill