686 research outputs found
Frequency-dependent (ac) Conduction in Disordered Composites: a Percolative Study
In a recent paper [Phys. Rev. B{\bf57}, 3375 (1998)], we examined in detail
the nonlinear (electrical) dc response of a random resistor cum tunneling bond
network (, introduced by us elsewhere to explain nonlinear response of
metal-insulator type mixtures). In this work which is a sequel to that paper,
we consider the ac response of the -based correlated () model.
Numerical solutions of the Kirchoff's laws for the model give a power-law
exponent (= 0.7 near ) of the modulus of the complex ac conductance at
moderately low frequencies, in conformity with experiments on various types of
disordered systems. But, at very low frequencies, it gives a simple quadratic
or linear dependence on the frequency depending upon whether the system is
percolating or not. We do also discuss the effective medium approximation
() of our and the traditional random network model, and discuss
their comparative successes and shortcomings.Comment: Revised and reduced version with 17 LaTeX pages plus 8 JPEG figure
Percolation Systems away from the Critical Point
This article reviews some effects of disorder in percolation systems even
away from the critical density p_c. For densities below p_c, the statistics of
large clusters defines the animals problem. Its relation to the directed
animals problem and the Lee-Yang edge singularity problem is described. Rare
compact clusters give rise to Griffiths singuraties in the free energy of
diluted ferromagnets, and lead to a very slow relaxation of magnetization. In
biassed diffusion on percolation clusters, trapping in dead-end branches leads
to asymptotic drift velocity becoming zero for strong bias, and very slow
relaxation of velocity near the critical bias field.Comment: Minor typos fixed. Submitted to Praman
Systematic review of allelic exchange experiments aimed at identifying mutations that confer drug resistance in Mycobacterium tuberculosis
First published online: September 20, 2013BACKGROUND:
Improving our understanding of the relationship between the genotype and the drug resistance phenotype of Mycobacterium tuberculosis will aid the development of more accurate molecular diagnostics for drug-resistant tuberculosis. Studies that use direct genetic manipulation to identify the mutations that cause M. tuberculosis drug resistance are superior to associational studies in elucidating an individual mutation's contribution to the drug resistance phenotype.
METHODS:
We systematically reviewed the literature for publications reporting allelic exchange experiments in any of the resistance-associated M. tuberculosis genes. We included studies that introduced single point mutations using specialized linkage transduction or site-directed/in vitro mutagenesis and documented a change in the resistance phenotype.
RESULTS:
We summarize evidence supporting the causal relationship of 54 different mutations in eight genes (katG, inhA, kasA, embB, embC, rpoB, gyrA and gyrB) and one intergenic region (furA-katG) with resistance to isoniazid, the rifamycins, ethambutol and fluoroquinolones. We observed a significant role for the strain genomic background in modulating the resistance phenotype of 21 of these mutations and found examples of where the same drug resistance mutations caused varying levels of resistance to different members of the same drug class.
CONCLUSIONS:
This systematic review highlights those mutations that have been shown to causally change phenotypic resistance in M. tuberculosis and brings attention to a notable lack of allelic exchange data for several of the genes known to be associated with drug resistance.This work was supported by the Portuguese Foundation for Science and Technology (FCT) (SFRH/BD/33902/2009 to H. N.-G.), the National Institutes of Health/Fogarty International Center (1K01 TW009213 to K.R.J.), departmental funds of the pulmonary division of Massachusetts General Hospital to M. R. F. and the National Institutes of Health/NIAID (U19 A1076217 to M.B.M.)
Identification of protein biomarkers for prediction of response to platinum-based treatment regimens in patients with non-small cell lung cancer
The majority of patients with resected stage II-IIIA non-small cell lung cancer (NSCLC) are treated with platinum-based adjuvant chemotherapy (ACT) in a one-size-fits-all approach. However, a significant number of patients do not derive clinical benefit, and no predictive patient selection biomarker is currently available. Using mass spectrometry-based proteomics, we have profiled tumour resection material of 2 independent, multi-centre cohorts of in total 67 patients with NSCLC who underwent ACT. Unsupervised cluster analysis of both cohorts revealed a poor response/survival sub-cluster composed of ~ 25% of the patients, that displayed a strong epithelial-mesenchymal transition signature and stromal phenotype. Beyond this stromal sub-population, we identified and validated platinum response prediction biomarker candidates involved in pathways relevant to the mechanism of action of platinum drugs, such as DNA damage repair, as well as less anticipated processes such as those related to the regulation of actin cytoskeleton. Integration with pre-clinical proteomics data supported a role for several of these candidate proteins in platinum response prediction. Validation of one of the candidates (HMGB1) in a third independent patient cohort using immunohistochemistry highlights the potential of translating these proteomics results to clinical practice.</p
mRNA Display Selection of an Optimized MDM2-Binding Peptide That Potently Inhibits MDM2-p53 Interaction
p53 is a tumor suppressor protein that prevents tumorigenesis through cell cycle arrest or apoptosis of cells in response to cellular stress such as DNA damage. Because the oncoprotein MDM2 interacts with p53 and inhibits its activity, MDM2-p53 interaction has been a major target for the development of anticancer drugs. While previous studies have used phage display to identify peptides (such as DI) that inhibit the MDM2-p53 interaction, these peptides were not sufficiently optimized because the size of the phage-displayed random peptide libraries did not cover all of the possible sequences. In this study, we performed selection of MDM2-binding peptides from large random peptide libraries in two stages using mRNA display. We identified an optimal peptide named MIP that inhibited the MDM2-p53 and MDMX-p53 interactions 29- and 13-fold more effectively than DI, respectively. Expression of MIP fused to the thioredoxin scaffold protein in living cells by adenovirus caused stabilization of p53 through its interaction with MDM2, resulting in activation of the p53 pathway. Furthermore, expression of MIP also inhibited tumor cell proliferation in a p53-dependent manner more potently than DI. These results show that two-stage, mRNA-displayed peptide selection is useful for the rapid identification of potent peptides that target oncoproteins
Rapid intraoperative insulin assay: a novel method to differentiate insulinoma from nesidioblastosis in the pediatric patient
Introduction: Hyperinsulinism is the most common cause of recurrent and persistent hypoglycemia in infancy and childhood. Causes can include nesidioblastosis, pancreatic islet cell tumors such as insulinoma, and associations with multiple endocrine neoplasia syndromes. Although new, improved imaging techniques have allowed for more precise preoperative localization of insulinomas, the differentiation of nesidioblastosis and insulinoma, particularly in children, can be challenging. To improve intraoperative localization and confirmation of successful resection of insulinoma, a novel hormonal assay, the rapid intraoperative insulin assay, is reported for the first time in a pediatric patient. This intraoperative radioimmunoassay for insulin yields results within several minutes and confirms complete resection of insulinoma. Case description: We present a case of pancreatic insulinoma in a child with symptoms of severe hypoglycemia, causing seizures. The insulinoma was enucleated laparoscopically, and rapid intra-operative insulin assay used to determine the success of the procedure. Discussion and evaluation: This rapid intra-operative test provides a valuable adjunct for determining complete excision in complicated cases of recurrent or questionable insulinoma. Although not a common problem, for pediatric patients in whom the diagnosis is not clear, this test may provide a novel approach to confirming disease. Conclusion: We propose the use of this assay in facilitating intra-operative resection and confirmation of complete excision in pediatric patients. This population may especially benefit from this novel assay to confirm complete resection and to differentiate multiple etiologies of hyperinsulinism
Effective Rheology of Bubbles Moving in a Capillary Tube
We calculate the average volumetric flux versus pressure drop of bubbles
moving in a single capillary tube with varying diameter, finding a square-root
relation from mapping the flow equations onto that of a driven overdamped
pendulum. The calculation is based on a derivation of the equation of motion of
a bubble train from considering the capillary forces and the entropy production
associated with the viscous flow. We also calculate the configurational
probability of the positions of the bubbles.Comment: 4 pages, 1 figur
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