Streamer evolution arrest governed amplified AC breakdown strength of graphene and CNT colloids

The present article experimentally explores the concept of large improving the AC dielectric breakdown strength of insulating mineral oils by the addition of trace amounts of graphene or CNTs to form stable dispersions. The nano-oils infused with these nanostructures of high electronic conductance indicate superior AC dielectric behaviour in terms of augmented breakdown strength compared to the base oils. Experimental observations of two grades of synthesized graphene and CNT nano-oils show that the nanomaterials not only improve the average breakdown voltage but also significantly improve the reliability and survival probabilities of the oils under AC high voltage stressing. Improvement of the tune of ~ 70-80 % in the AC breakdown voltage of the oils has been obtained via the present concept. The present study examines the reliability of such nano-colloids with the help of two parameter Weibull distribution and the oils show greatly augmented electric field bearing capacity at both standard survival probability values of 5 % and 63.3 %. The fundamental mechanism responsible for such observed outcomes is reasoned to be delayed streamer development and reduced streamer growth rates due to effective electron scavenging by the nanostructures from the ionized liquid insulator. A mathematical model based on the principles of electron scavenging is proposed to quantify the amount of electrons scavenged by the nanostructures. The same is then employed to predict the enhanced AC breakdown voltage and the experimental values are found to match well with the model predictions. The present study can have strong implications in efficient, reliable and safer operation of real life AC power systems

Evaluation of Methods for Estimating Time to Steady State with Examples from Phase 1 Studies

An overview is provided of the methodologies used in determining the time to steady state for Phase 1 multiple dose studies. These methods include NOSTASOT (no-statistical-significance-of-trend), Helmert contrasts, spline (quadratic) regression, effective half life for accumulation, nonlinear mixed effects modeling, and Bayesian approach using Markov Chain Monte Carlo (MCMC) methods. For each methodology we describe its advantages and disadvantages. The first two methods do not require any distributional assumptions for the pharmacokinetic (PK) parameters and are limited to average assessment of steady state. Also spline regression which provides both average and individual assessment of time to steady state does not require any distributional assumptions for the PK parameters. On the other hand, nonlinear mixed effects modeling and Bayesian hierarchical modeling which allow for the estimation of both population and subject-specific estimates of time to steady state do require distributional assumptions on PK parameters. The current investigation presents eight case studies for which the time to steady state was assessed using the above mentioned methodologies. The time to steady state estimates obtained from nonlinear mixed effects modeling, Bayesian hierarchal approach, effective half life, and spline regression were generally similar

Inflammatory arthritis in HIV positive patients: A practical guide

Background: Musculoskeletal manifestations of the human immunodeficiency virus (HIV) have been described since the outset of the global HIV epidemic. Articular syndromes that have been described in association with HIV include HIV-associated arthropathy, seronegative spondyloarthropathies (SPA) (reactive arthritis, psoriatic arthritis (PsA) and undifferentiated SPA), rheumatoid arthritis (RA) and painful articular syndrome. Methods: We carried out a computer-assisted search of PubMed for the medical literature from January 1981 to January 2015 using the keywords HIV, acquired immune-deficiency syndrome, rheumatic manifestations, arthritis, spondyloarthropathy, anti-TNF and disease modifying antirheumatic drugs. Only English language literature was included and only studies involving adult human subjects were assessed. Results: There are challenges in the management of inflammatory arthritis in patients who are HIV-positive, including difficulties in the assessment of disease activity and limited information on the safety of immunosuppressive drugs in these individuals. Conclusions: This review focuses on the clinical characteristics of the inflammatory articular syndromes that have been described in association with HIV infection and discusses the therapeutic options for these patients

Preclinical electrogastrography in experimental pigs

Surface electrogastrography (EGG) is a non-invasive means of recording gastric myoelectric activity or slow waves from cutaneous leads placed over the stomach. This paper provides a comprehensive review of preclinical EGG. Our group recently set up and worked out the methods for EGG in experimental pigs. We gained our initial experience in the use of EGG in assessment of porcine gastric myoelectric activity after volume challenge and after intragastric administration of itopride and erythromycin. The mean dominant frequency in pigs is comparable with that found in humans. EGG in experimental pigs is feasible. Experimental EGG is an important basis for further preclinical projects in pharmacology and toxicology

Cardiac disease in patients with mucopolysaccharidosis: presentation, diagnosis and management

The mucopolysaccharidoses (MPSs) are inherited lysosomal storage disorders caused by the absence of functional enzymes that contribute to the degradation of glycosaminoglycans (GAGs). The progressive systemic deposition of GAGs results in multi-organ system dysfunction that varies with the particular GAG deposited and the specific enzyme mutation(s) present. Cardiac involvement has been reported in all MPS syndromes and is a common and early feature, particularly for those with MPS I, II, and VI. Cardiac valve thickening, dysfunction (more severe for left-sided than for right-sided valves), and hypertrophy are commonly present; conduction abnormalities, coronary artery and other vascular involvement may also occur. Cardiac disease emerges silently and contributes significantly to early mortality

BRD4-mediated repression of p53 is a target for combination therapy in AML

Acute myeloid leukemia (AML) is a typically lethal molecularly heterogeneous disease, with few broad-spectrum therapeutic targets. Unusually, most AML retain wild-type TP53, encoding the pro-apoptotic tumor suppressor p53. MDM2 inhibitors (MDM2i), which activate wild-type p53, and BET inhibitors (BETi), targeting the BET-family co-activator BRD4, both show encouraging pre-clinical activity, but limited clinical activity as single agents. Here, we report enhanced toxicity of combined MDM2i and BETi towards AML cell lines, primary human blasts and mouse models, resulting from BETi’s ability to evict an unexpected repressive form of BRD4 from p53 target genes, and hence potentiate MDM2i-induced p53 activation. These results indicate that wild-type TP53 and a transcriptional repressor function of BRD4 together represent a potential broad-spectrum synthetic therapeutic vulnerability for AML

iTRAQ proteomic analysis of extracellular matrix remodeling in aortic valve disease

Degenerative aortic stenosis (AS) is the most common worldwide cause of valve replacement. The aortic valve is a thin, complex, layered connective tissue with compartmentalized extracellular matrix (ECM) produced by specialized cell types, which directs blood flow in one direction through the heart. There is evidence suggesting remodeling of such ECM during aortic stenosis development. Thus, a better characterization of the role of ECM proteins in this disease would increase our understanding of the underlying molecular mechanisms. Aortic valve samples were collected from 18 patients which underwent aortic valve replacement (50% males, mean age of 74 years) and 18 normal control valves were obtained from necropsies (40% males, mean age of 69 years). The proteome of the samples was analyzed by 2D-LC MS/MS iTRAQ methodology. The results showed an altered expression of 13 ECM proteins of which 3 (biglycan, periostin, prolargin) were validated by Western blotting and/or SRM analyses. These findings are substantiated by our previous results demonstrating differential ECM protein expression. The present study has demonstrated a differential ECM protein pattern in individuals with AS, therefore supporting previous evidence of a dynamic ECM remodeling in human aortic valves during AS development

A traditional way to combat against Streptococcus mutans

Purpose: This study was conducted to evaluate and compare the antimicrobial activity of conventional Glass ionomer cement, Glass ionomer cement (GIC) with 0.1% (w/w) epigallocatechin-3-gallate (EGCG) and Glass ionomer cement with 1% (w/w) Curcuma longa against streptococcus mutans.Methods: Children of age group 5-9 years, irrespective of sex, race and socioeconomic status with at least 3 cavitated dentinal lesions in primary molars clinically involving occlusal surface suitable for ART were selected.The dentinal samples were collected three times from each carious tooth, viz. baseline (before excavation of caries), after hand excavation of caries and after 7 days of restoration. The dentinal samples were subjected to microbiological evaluation for Streptococcus mutans count.Results: Experimental groups (Group II and group III) showed statistically significant reduction in Streptococcus mutans counts compared to control group (Conventional Glass ionomer cement). Group II i.e. (Glass ionomer cement with 0.1% (w/w) EGCG) showed significant reduction than Group III i.e. (Glass ionomer cement with 1% (w/w) Curcuma longa).Conclusion: ART technique was successful in reducing the streptococcus mutans load in a carious cavity but significant numbers of residual microbes were still found to be present even after the carious tissue was removed. Restoration of the cavity using EGCG and turmeric modified GIC was able to markedly reduce the S.mutans counts compared to conventional GIC.Â