2,601 research outputs found

    Effect of van-Hove singularities in single-walled carbon nanotube leads on transport through double quantum dot system

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    The double quantum dot system with single-walled metallic armchair carbon nanotube leads has been studied using Non-equilibrium Green function in the Keldysh formalism. The effect of relative spacing between the energy levels of the dots, interdot tunneling matrix-element, interdot Coulomb interaction and van-Hove singularities in density of states characteristics of quasi-one-dimensional carbon nanotube leads on the conductance of the double quantum dot system has been studied. The conductance and dot occupancies are calculated at finite temperature. It is observed that the density of states of the carbon nanotube leads play a significant role in determining the conductance profile. In particular, whenever the chemical potential of the isolated double quantum dot system is aligned with the position of a van-Hove singularity in the density of states of armchair carbon nanotube leads, the height of the corresponding conductance peak falls considerably. It is further observed that the suppression in the heights of the alternate peaks depends on the relative positions of the energy levels of the dots and their magnitude of separation.Comment: 16 pages and 16 figure

    Unexpected cell type-dependent effects of autophagy on polyglutamine aggregation revealed by natural genetic variation in C. elegans.

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    BACKGROUND: Monogenic protein aggregation diseases, in addition to cell selectivity, exhibit clinical variation in the age of onset and progression, driven in part by inter-individual genetic variation. While natural genetic variants may pinpoint plastic networks amenable to intervention, the mechanisms by which they impact individual susceptibility to proteotoxicity are still largely unknown. RESULTS: We have previously shown that natural variation modifies polyglutamine (polyQ) aggregation phenotypes in C. elegans muscle cells. Here, we find that a genomic locus from C. elegans wild isolate DR1350 causes two genetically separable aggregation phenotypes, without changing the basal activity of muscle proteostasis pathways known to affect polyQ aggregation. We find that the increased aggregation phenotype was due to regulatory variants in the gene encoding a conserved autophagy protein ATG-5. The atg-5 gene itself conferred dosage-dependent enhancement of aggregation, with the DR1350-derived allele behaving as hypermorph. Surprisingly, increased aggregation in animals carrying the modifier locus was accompanied by enhanced autophagy activation in response to activating treatment. Because autophagy is expected to clear, not increase, protein aggregates, we activated autophagy in three different polyQ models and found a striking tissue-dependent effect: activation of autophagy decreased polyQ aggregation in neurons and intestine, but increased it in the muscle cells. CONCLUSIONS: Our data show that cryptic natural variants in genes encoding proteostasis components, although not causing detectable phenotypes in wild-type individuals, can have profound effects on aggregation-prone proteins. Clinical applications of autophagy activators for aggregation diseases may need to consider the unexpected divergent effects of autophagy in different cell types

    Excitation of surface plasmons in thin noble metallic film of copper, silver and gold paper

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    The formation of surface plasmons in a different type of noble metallic film was successfully simulated using MATLAB program software. The thicknesses of copper, silver and gold metal films were varied between 20 nm to 80 nm. The narrowness and depth of surface plasmon resonance (SPR) curves were observed to determine the excitation of surface plasmons. The simulation results indicate that the maximum excitation of surface plasmons can be achieved by using silver thin film with thicknesses of 50 nm at the minimum reflectivity of 0.0038 a.u and full width at half maximum value of 0.2592°. The silver film that produces a deeper and sharper SPR curve has potential in the development of a low cost and high sensitivity of SPR sensing device

    Spectrum of neurological disorders presenting at a neurology clinic in tertiary care hospital in peshawar, pakistan

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    To ascertain the spectrum of different neurological disorders presenting at a tertiary care neurology clinic in Peshawar, Pakistan. Method: A prospective observational study was conducted of all presentations to the neurology clinic in Northwest General Hospital and Research Center, over a period of one year extending from 1st February, 2013 to 31st January, 2014. Study population included 9386 patients from the neurology clinic over the period of one year. The age distribution of all patients was variable; the youngest patient seen was 1 year old while the oldest was 92 years of age. Appropriate history and neurological examination was conducted by consultant neurologist and classified patients into neurological diseases according to the International Classification of Disease (ICD-10) codes for neurology. Statistical analyses were carried out using the software SPSS version 11 and qualitative variables were presented as percentages. Results: A total of 9386 patients were examined and classified into different neurological disorders according to the International Classification of Disease (ICD-10) codes for neurology. Headache was the most common presentation (24%), followed by Cerebrovascular diseases (22%) and Epilepsies (17%). Conclusion: Headache was the most commonclinical presentation for neurology consultation followed by Cerebrovascular accidents (CVA) and epilepsy respectively. Almost all the categories of neurological disorders i.e. Inflammatory, Infective, Neoplastic and Degenerative Diseases were seen in the outpatient neurology clinic

    A rare case of myasthenia gravis with coexisting muscular dystrophy

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    Myasthenia gravis (MG) is an autoimmune disease in which antibodies are directed against postsynaptic membrane of neuromuscular junction, resulting in muscle weakness and fatigability. We report a rare case of an 11 years old boy who was a known case of myasthenia gravis presented with progressive weakness and wasting of facial and limb musculature and was found to have coexisting muscular dystrophy most like facioscapulohumeral muscular dystrophy (FSHD)

    Association of FCGR3A and FCGR3B haplotypes with rheumatoid arthritis and primary Sjögren's syndrome [POSTER PRESENTATION]

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    Background Rheumatoid arthritis (RA) is an autoimmune disease that is thought to arise from a complex interaction between multiple genetic factors and environmental triggers. We have previously demonstrated an association between a Fc gamma receptor (FcγR) haplotype and RA in a cross-sectional cohort of RA patients. We have sought to confirm this association in an inception cohort of RA patients and matched controls. We also extended our study to investigate a second autoanti-body associated rheumatic disease, primary Sjögren's syndrome (PSS). Methods The FCGR3A-158F/V and FCGR3B-NA1/NA2 functional polymorphisms were examined for association in an inception cohort of RA patients (n = 448), and a well-characterised PSS cohort (n = 83) from the United Kingdom. Pairwise disequilibrium coefficients (D') were calculated in 267 Blood Service healthy controls. The EHPlus program was used to estimate haplotype frequencies for patients and controls and to determine whether significant linkage disequilibrium was present. A likelihood ratio test is performed to test for differences between the haplotype frequencies in cases and controls. A permutation procedure implemented in this program enabled 1000 permutations to be performed on all haplotype associations to assess significance. Results There was significant linkage disequilibrium between FCGR3A and FCGR3B (D' = -0.445, P = 0.001). There was no significant difference in the FCGR3A or FCGR3B allele or genotype frequencies in the RA or PSS patients compared with controls. However, there was a significant difference in the FCGR3A-FCGR3B haplotype distributions with increased homozygosity for the FCGR3A-FCGR3B 158V-NA2 haplotype in both our inception RA cohort (odds ratio = 2.15, 95% confidence interval = 1.1–4.2 P = 0.027) and PSS (odds ratio = 2.83, 95% confidence interval = 1.0–8.2, P = 0.047) compared with controls. The reference group for these analyses comprised individuals who did not possess a copy of the FCGR3A-FCGR3B 158V-NA2 haplotype. Conclusions We have confirmed our original findings of association between the FCGR3A-FCGR3B 158V-NA2 haplotype and RA in a new inception cohort of RA patients. This suggests that there may be an RA-susceptibility gene at this locus. The significant increased frequency of an identical haplotype in PSS suggests the FcγR genetic locus may contribute to the pathogenesis of diverse autoantibody-mediated rheumatic diseases

    Macroalgae Decrease Growth and Alter Microbial Community Structure of the Reef-Building Coral, Porites astreoides

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    This is the publisher’s final pdf. The published article is copyrighted by the Public Library of Science and can be found at: http://www.plosone.org/home.action.With the continued and unprecedented decline of coral reefs worldwide, evaluating the factors that contribute to coral demise is of critical importance. As coral cover declines, macroalgae are becoming more common on tropical reefs. Interactions between these macroalgae and corals may alter the coral microbiome, which is thought to play an important role in colony health and survival. Together, such changes in benthic macroalgae and in the coral microbiome may result in a feedback mechanism that contributes to additional coral cover loss. To determine if macroalgae alter the coral microbiome, we conducted a field-based experiment in which the coral Porites astreoides was placed in competition with five species of macroalgae. Macroalgal contact increased variance in the coral-associated microbial community, and two algal species significantly altered microbial community composition. All macroalgae caused the disappearance of a γ-proteobacterium previously hypothesized to be an important mutualist of P. astreoides. Macroalgal contact also triggered: 1) increases or 2) decreases in microbial taxa already present in corals, 3) establishment of new taxa to the coral microbiome, and 4) vectoring and growth of microbial taxa from the macroalgae to the coral. Furthermore, macroalgal competition decreased coral growth rates by an average of 36.8%. Overall, this study found that competition between corals and certain species of macroalgae leads to an altered coral microbiome, providing a potential mechanism by which macroalgae-coral interactions reduce coral health and lead to coral loss on impacted reefs

    Comparison of nuisance parameters in pediatric versus adult randomized trials: a meta-epidemiologic empirical evaluation

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    BACKGROUND We wished to compare the nuisance parameters of pediatric vs. adult randomized-trials (RCTs) and determine if the latter can be used in sample size computations of the former. METHODS In this meta-epidemiologic empirical evaluation we examined meta-analyses from the Cochrane Database of Systematic-Reviews, with at least one pediatric-RCT and at least one adult-RCT. Within each meta-analysis of binary efficacy-outcomes, we calculated the pooled-control-group event-rate (CER) across separately all pediatric and adult-trials, using random-effect models and subsequently calculated the control-group event-rate risk-ratio (CER-RR) of the pooled-pediatric-CERs vs. adult-CERs. Within each meta-analysis with continuous outcomes we calculated the pooled-control-group effect standard deviation (CE-SD) across separately all pediatric and adult-trials and subsequently calculated the CE-SD-ratio of the pooled-pediatric-CE-SDs vs. adult-CE-SDs. We then calculated across all meta-analyses the pooled-CER-RRs and pooled-CE-SD-ratios (primary endpoints) and the pooled-magnitude of effect-sizes of CER-RRs and CE-SD-ratios using REMs. A ratio < 1 indicates that pediatric trials have smaller nuisance parameters than adult trials. RESULTS We analyzed 208 meta-analyses (135 for binary-outcomes, 73 for continuous-outcomes). For binary outcomes, pediatric-RCTs had on average 10% smaller CERs than adult-RCTs (summary-CE-RR: 0.90; 95% CI: 0.83, 0.98). For mortality outcomes the summary-CE-RR was 0.48 (95% CIs: 0.31, 0.74). For continuous outcomes, pediatric-RCTs had on average 26% smaller CE-SDs than adult-RCTs (summary-CE-SD-ratio: 0.74). CONCLUSIONS Clinically relevant differences in nuisance parameters between pediatric and adult trials were detected. These differences have implications for design of future studies. Extrapolation of nuisance parameters for sample-sizes calculations from adult-trials to pediatric-trials should be cautiously done
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