198 research outputs found

    Use Of Laboratory Geophysical And Geotechnical Investigation Methods To Characterize Gypsum Rich Soils

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    Gypsum rich soils are found in many parts of the world, particularly in arid and semi-arid regions. Most gypsum occurs in the form of evaporites, which are minerals that precipitate out of water due to a high rate of evaporation and a high mineral concentration. Gypsum rich soils make good foundation material under dry conditions but pose major engineering hazards when exposed to water. Gypsum acts as a weak cementing material and has a moderate solubility of about 2.5 g/liter. The dissolution of gypsum causes the soils to undergo unpredictable collapse settlement leading to severe structural damages. The damages incur heavy financial losses every year. The objective of this research was to use geophysical methods such as free-free resonant column testing and electrical resistivity testing to characterize gypsum rich soils based on the shear wave velocity and electrical resistivity values. The geophysical testing methods could provide quick, non-intrusive and cost-effective methodologies to screen sites known to contain gypsum deposits. Reconstituted specimens of ground gypsum and quartz sand were prepared in the laboratory with varying amounts of gypsum and tested. Additionally geotechnical tests such as direct shear strength tests and consolidation tests were conducted to estimate the shear strength parameters (drained friction angle and cohesion) and the collapse potential of the soils. The effect of gypsum content on the geophysical and geotechnical parameters of soil was of particular interest. It was found that gypsum content had an influence on the shear wave velocity but had minimal effect on electrical resistivity. The collapsibility and friction angle of the soil increased with increase in gypsum. The information derived from the geophysical and geotechnical tests was used to develop statistical design equations and correlations to estimate gypsum content and soil collapse potential

    Impact of dialysis modality on survival of new ESRD patients with congestive heart failure in the United States

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    Impact of dialysis modality on survival of new ESRD patients with congestive heart failure in the United States.BackgroundIt is hypothesized, but not proven, that peritoneal dialysis might be the optimal treatment for end-stage renal disease (ESRD) patients with established congestive heart failure (CHF) through better volume regulation compared with hemodialysis.MethodsNational incidence data on 107,922 new ESRD patients from the Center for Medicare and Medicaid Services (CMS) Medical Evidence Form were used to test the hypothesis that peritoneal dialysis was superior to hemodialysis in prolonging survival of patients with CHF. Nonproportional Cox regression models evaluated the relative hazard of death for patients with and without CHF by dialysis modality using primarily the intent-to-treat but also the as-treated approach. Diabetics and nondiabetics were analyzed separately.ResultsThe overall prevalence of CHF was 33% at ESRD initiation. There were 27,149 deaths (25.2%), 5423 transplants (5%), and 3753 (3.5%) patients lost to follow-up over 2years. Adjusted mortality risks were significantly higher for patients with CHF treated with peritoneal dialysis than hemodialysis [diabetics, relative risk (RR) = 1.30, 95% confidence interval (CI) 1.20 to 1.41; nondiabetics, RR = 1.24, 95% CI 1.14 to 1.35]. Among patients without CHF, adjusted mortality risk were higher only for diabetic patients treated with peritoneal dialysis compared with hemodialysis (RR = 1.11, 95% CI 1.02 to 1.21) while nondiabetics had similar survival on peritoneal dialysis or hemodialysis (RR = 0.97, 95% CI 0.91 to 1.04).ConclusionNew ESRD patients with a clinical history of CHF experienced poorer survival when treated with peritoneal dialysis compared with hemodialysis. These data suggest that peritoneal dialysis may not be the optimal choice for new ESRD patients with CHF perhaps through impaired volume regulation and worsening cardiomyopathy

    Non-Supersymmetric Attractors in R2R^2 Gravities

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    We investigate the attractor mechanism for spherically symmetric extremal black holes in a theory of general R2R^2 gravity in 4-dimensions, coupled to gauge fields and moduli fields. For the general R2R^2 theory, we look for solutions which are analytic near the horizon, show that they exist and enjoy the attractor behavior. The attractor point is determined by extremization of an effective potential at the horizon. This analysis includes the backreaction and supports the validity of non-supersymmetric attractors in the presence of higher derivative interactions. To include a wider class of solutions, we continue our analysis for the specific case of a Gauss-Bonnet theory which is non-topological, due to the coupling of Gauss-Bonnet terms to the moduli fields. We find that the regularity of moduli fields at the horizon is sufficient for attractor behavior. For the non-analytic sector, this regularity condition in turns implies the minimality of the effective potential at the attractor point.Comment: 19 pages, 2 figure

    Preclinical assessment of ulixertinib, a novel ERK1/2 inhibitor

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    Ulixertinib (BVD-523) is a novel and selective reversible inhibitor of ERK1/ERK2. In xenograft studies it inhibited tumor growth in BRAF-mutant melanoma and colorectal xenografts as well as KRAS-mutant colorectal and pancreatic models. Ulixertinib is currently in Phase I clinical development for the treatment of advance solid tumors. The objective of the study is to assess the metabolic stability (in various pre-clinical and human liver microsomes/hepatocytes), permeability, protein binding, CYP inhibition, CYP induction and CYP phenotyping of ulixertinib. We have also studied the oral and intravenous pharmacokinetics of ulixertinib in mice, rats and dogs. Ulixertinib was found to be moderately to highly stable in various liver microsomes/hepatocytes tested. It is a medium permeable (2.67 x 10-6 cm /sec) drug and a substrate for efflux (efflux ratio: 3.02) in Caco-2 model. Ulixertinib was highly bound to plasma proteins. CYPs involved in its limited metabolism and it is CYP inhibition IC50 ranged between 10-20 μM. Post oral administration ulixertinib exhibited early Tmax (0.50-0.75 h) in mice and rats indicating absorption was rapid, however in dogs Tmax attained at 2 h. The half-life (t½) of ulixertinib by intravenous and oral routes ranged between 1.0-2.5 h across the species. Clearance and volume of distribution by intravenous route for ulixertinib were found to be 6.24 mL/min/kg and 0.56 L/kg; 1.67 mL/min/kg and 0.36 L/kg and 15.5 mL/min/kg and 1.61 L/kg in mice, rats and dogs, respectively. Absolute oral bioavailability in mice and rats was > 92 %, however in dogs it was 34 %

    D-branes in PP-wave light cone string field theory

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    The cubic interaction vertex and the dynamical supercharges are constructed for open strings ending on D7-branes, in light-cone superstring field theory in PP-wave background. In this context, we write down the symmetry generators in terms of the relevant group structure: SU(2) x SU(2) x SO(2) x SO(2), originating from the eight transverse directions in the PP-wave background and use the expressions to explicitly construct the vertex at the level of stringy zero modes. The results are further generalized to include all the stringy excitations as well.Comment: 30 pages, correction in eqn. (4.28), few equations (appendix), Comments (p.17-18) and a reference (no. 58) added, typo is corrected in eqn. (4.5

    Fully Resolved assembly of Cryptosporidium Parvum

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    BACKGROUND: Cryptosporidium parvum is an apicomplexan parasite commonly found across many host species with a global infection prevalence in human populations of 7.6%. Understanding its diversity and genomic makeup can help in fighting established infections and prohibiting further transmission. The basis of every genomic study is a high-quality reference genome that has continuity and completeness, thus enabling comprehensive comparative studies. FINDINGS: Here, we provide a highly accurate and complete reference genome of Cryptosporidium parvum. The assembly is based on Oxford Nanopore reads and was improved using Illumina reads for error correction. We also outline how to evaluate and choose from different assembly methods based on 2 main approaches that can be applied to other Cryptosporidium species. The assembly encompasses 8 chromosomes and includes 13 telomeres that were resolved. Overall, the assembly shows a high completion rate with 98.4% single-copy BUSCO genes. CONCLUSIONS: This high-quality reference genome of a zoonotic IIaA17G2R1 C. parvum subtype isolate provides the basis for subsequent comparative genomic studies across the Cryptosporidium clade. This will enable improved understanding of diversity, functional, and association studies

    The ventilation of buildings and other mitigating measures for COVID-19: a focus on wintertime.

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    The year 2020 has seen the emergence of a global pandemic as a result of the disease COVID-19. This report reviews knowledge of the transmission of COVID-19 indoors, examines the evidence for mitigating measures, and considers the implications for wintertime with a focus on ventilation.This work was undertaken as a contribution to the Rapid Assistance in Modelling the Pandemic (RAMP) initiative, coordinated by the Royal Society

    ADP Ribosylation Factor Like 2 (Arl2) Regulates Breast Tumor Aggressivity in Immunodeficient Mice

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    We have previously reported that ADP ribosylation factor like 2 (Arl2), a small GTPase, content influences microtubule dynamics and cell cycle distribution in breast tumor cells, as well as the degree and distribution of phosphorylated P53. Here we show, in two different human breast adenocarcinoma models, that Arl2 content has a major impact on breast tumor cell aggressivity both in vitro and in vivo. Cells with reduced content of Arl2 displayed reduced contact inhibition, increased clonogenic or cluster formation as well as a proliferative advantage over control cells in an in vitro competition assay. These cells also caused larger tumors in SCID mice, a phenotype which was mimicked by the in vivo administration of siRNA directed against Arl2. Cells with increased Arl2 content displayed reduced aggressivity, both in vitro and in vivo, with enhanced necrosis and were also found to contain increased PP2A phosphatase activity. A rt-PCR analysis of fresh human tumor breast samples suggested that low Arl2 expression was associated with larger tumor size and greater risk of lymph node involvement at diagnosis. These data underline the role of Arl2, a small GTPase, as an important regulator of breast tumor cell aggressivity, both in vitro and in vivo

    Autoinhibition of TBCB regulates EB1-mediated microtubule dynamics

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    Tubulin cofactors (TBCs) participate in the folding, dimerization, and dissociation pathways of the tubulin dimer. Among them, TBCB and TBCE are two CAP-Gly domain-containing proteins that interact and dissociate the tubulin dimer. Here we show how TBCB localizes at spindle and midzone microtubules during mitosis. Furthermore, the motif DEI/M-COO– present in TBCB, which is similar to the EEY/F-COO– element characteristic of EB proteins, CLIP-170, and α-tubulin, is required for TBCE–TBCB heterodimer formation and thus for tubulin dimer dissociation. This motif is responsible for TBCB autoinhibition, and our analysis suggests that TBCB is a monomer in solution. Mutants of TBCB lacking this motif are derepressed and induce microtubule depolymerization through an interaction with EB1 associated to microtubule tips. TBCB is also able to bind to the chaperonin complex CCT containing α-tubulin, suggesting that it could escort tubulin to facilitate its folding and dimerization, recycling or degradation
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