A semi-implicit finite-difference time-domain thin-wire (TW) scheme with a relaxed stability condition is proposed for modelling effective surface plasmons in waveguide metamaterials. Its formulation ...is based on introducing the Newmark-Beta method into the TW formulation based on the contour-path integral of Maxwell's equations around a wire. The resultant scheme is magnetically implicit. Its stability, accuracy and efficiency are assessed in the application to a wire-added parallel-plate waveguide perturbed with a small gap.
Drug resistance commonly occurs when treating immunocompromised patients who have fungal infections. Curcumin, is a compound isolated from Curcuma longa, has been reported to inhibit drug efflux in ...several human cell lines and nonpathogenic budding yeast Saccharomyces cerevisiae cells that overexpresses the ATP‐binding cassette (ABC) transporters S. cerevisiae Pdr5p and pathogenic Candida albicans Cdr1p and Cdr2p. The aim of this study was to examine the effects of curcumin on multidrug resistance in a wild‐type strain of the budding yeast with an intrinsic expression system of multidrug efflux‐related genes. The antifungal activity of dodecanol alone was temporary against S. cerevisiae; however, restoration of cell viability was completely inhibited when the cells were co‐treated with dodecanol and curcumin. Furthermore, restriction of rhodamine 6G (R6G) efflux from the cells and intracellular accumulation of R6G were observed with curcumin treatment. Reverse transcription‐polymerase chain reaction analysis revealed that curcumin reduced the dodecanol‐induced overexpression of the ABC transporter‐related genes PDR1, PDR3 and PDR5 to their control levels in untreated cells. Curcumin can directly restrict the glucose‐induced drug efflux and inhibits the expression of the ABC transporter gene PDR5, and can thereby inhibit the efflux of dodecanol from S. cerevisiae cells. Curcumin is effective in potentiating the efficacy of antifungal drugs via its effects on ABC transporters.
Significance and Impact of the Study
Drug resistance is common in immunocompromised patients with fungal infections. Curcumin, isolated from Curcuma longa, inhibits drug efflux in nonpathogenic budding yeast Saccharomyces cerevisiae cells overexpressing ABC transporters S. cerevisiae Pdr5p and pathogenic Candida albicans Cdr1p and Cdr2p. We examined the effects of curcumin on multidrug resistance in a wild‐type strain of the budding yeast with an intrinsic expression system of multidrug efflux‐related genes. Curcumin directly inhibited drug efflux and also suppressed the PDR5 expression, thereby enhancing the antifungal effects. Thus, curcumin potentially promotes the efficacy of antifungals via its effects on ABC transporters in wild‐type fungal strains.
Significance and Impact of the Study: Drug resistance is common in immunocompromised patients with fungal infections. Curcumin, isolated from Curcuma longa, inhibits drug efflux in nonpathogenic budding yeast Saccharomyces cerevisiae cells overexpressing ABC transporters S. cerevisiae Pdr5p and pathogenic Candida albicans Cdr1p and Cdr2p. We examined the effects of curcumin on multidrug resistance in a wild‐type strain of the budding yeast with an intrinsic expression system of multidrug efflux‐related genes. Curcumin directly inhibited drug efflux and also suppressed the PDR5 expression, thereby enhancing the antifungal effects. Thus, curcumin potentially promotes the efficacy of antifungals via its effects on ABC transporters in wild‐type fungal strains.
The existence of electronic symmetry breaking in the underdoped cuprates and its disappearance with increased hole density p are now widely reported. However, the relation between this transition and ...the momentum-space ($\overrightarrow{\mathrm{k}}$-space) electronic structure underpinning the superconductivity has not yet been established. Here, we visualize the $\overrightarrow{\mathrm{Q}}=0$ = 0 (intra–unit-cell) and $\overrightarrow{\mathrm{Q}}\ne 0$ (density-wave) broken-symmetry states, simultaneously with the coherent $\overrightarrow{\mathrm{k}}$-space topology, for Bi2Sr2CaCu2O8+δ samples spanning the phase diagram 0.06 ≤ p ≤ 0.23. We show that the electronic symmetry-breaking tendencies weaken with increasing p and disappear close to a critical doping pc = 0.19. Concomitantly, the coherent $\overrightarrow{\mathrm{k}}$-space topology undergoes an abrupt transition, from arcs to closed contours, at the same pc. These data reveal that the $\overrightarrow{\mathrm{k}}$-space topology transformation in cuprates is linked intimately with the disappearance of the electronic symmetry breaking at a concealed critical point.
Neuromyelitis optica spectrum disorder (NMOSD) is a relapsing, autoimmune, inflammatory disorder that typically affects the optic nerves and spinal cord. At least two thirds of cases are associated ...with aquaporin-4 antibodies (AQP4-IgG) and complement-mediated damage to the central nervous system. In a previous small, open-label study involving patients with AQP4-IgG-positive disease, eculizumab, a terminal complement inhibitor, was shown to reduce the frequency of relapse.
In this randomized, double-blind, time-to-event trial, 143 adults were randomly assigned in a 2:1 ratio to receive either intravenous eculizumab (at a dose of 900 mg weekly for the first four doses starting on day 1, followed by 1200 mg every 2 weeks starting at week 4) or matched placebo. The continued use of stable-dose immunosuppressive therapy was permitted. The primary end point was the first adjudicated relapse. Secondary outcomes included the adjudicated annualized relapse rate, quality-of-life measures, and the score on the Expanded Disability Status Scale (EDSS), which ranges from 0 (no disability) to 10 (death).
The trial was stopped after 23 of the 24 prespecified adjudicated relapses, given the uncertainty in estimating when the final event would occur. The mean (±SD) annualized relapse rate in the 24 months before enrollment was 1.99±0.94; 76% of the patients continued to receive their previous immunosuppressive therapy during the trial. Adjudicated relapses occurred in 3 of 96 patients (3%) in the eculizumab group and 20 of 47 (43%) in the placebo group (hazard ratio, 0.06; 95% confidence interval CI, 0.02 to 0.20; P<0.001). The adjudicated annualized relapse rate was 0.02 in the eculizumab group and 0.35 in the placebo group (rate ratio, 0.04; 95% CI, 0.01 to 0.15; P<0.001). The mean change in the EDSS score was -0.18 in the eculizumab group and 0.12 in the placebo group (least-squares mean difference, -0.29; 95% CI, -0.59 to 0.01). Upper respiratory tract infections and headaches were more common in the eculizumab group. There was one death from pulmonary empyema in the eculizumab group.
Among patients with AQP4-IgG-positive NMOSD, those who received eculizumab had a significantly lower risk of relapse than those who received placebo. There was no significant between-group difference in measures of disability progression. (Funded by Alexion Pharmaceuticals; PREVENT ClinicalTrials.gov number, NCT01892345; EudraCT number, 2013-001150-10.).
Genealogical data are an important source of evidence for delimiting species, yet few statistical methods are available for calculating the probabilities associated with different species ...delimitations. Bayesian species delimitation uses reversible-jump Markov chain Monte Carlo (rjMCMC) in conjunction with a user-specified guide tree to estimate the posterior distribution for species delimitation models containing different numbers of species. We apply Bayesian species delimitation to investigate the speciation history of forest geckos (Hemidactylus fasciatus) from tropical West Africa using five nuclear loci (and mtDNA) for 51 specimens representing 10 populations. We find that species diversity in H. fasciatus is currently underestimated, and describe three new species to reflect the most conservative estimate for the number of species in this complex. We examine the impact of the guide tree, and the prior distributions on ancestral population sizes (θ) and root age (τ0), on the posterior probabilities for species delimitation. Mis-specification of the guide tree or the prior distribution for θ can result in strong support for models containing more species. We describe a new statistic for summarizing the posterior distribution of species delimitation models, called speciation probabilities, which summarize the posterior support for each speciation event on the starting guide tree.
The State and Fate of Himalayan Glaciers Bolch, T.; Kulkarni, A.; Kääb, A. ...
Science (American Association for the Advancement of Science),
04/2012, Volume:
336, Issue:
6079
Journal Article
Peer reviewed
Open access
Himalayan gladers are a focus of public and scientific debate. Prevailing uncertainties are of major concern because some projections of their future have serious implications for water resources. ...Most Himalayan glaciers are losing mass at rates similar to glaciers elsewhere, except for emerging indications of stability or mass gain in the Karakoram. A poor understanding of the processes affecting them, combined with the diversity of climatic conditions and the extremes of topographical relief within the region, makes projections speculative. Nevertheless, it is unlikely that dramatic changes in total runoff will occur soon, although continuing shrinkage outside the Karakoram will increase the seasonally of runoff, affect irrigation and hydropower, and alter hazards.
Parabens have been widely used as antimicrobial preservatives in cosmetics, pharmaceuticals, foods and beverages. Commonly, methyl‐, ethyl‐, propyl‐ and butylparaben are used independently or in ...combination to maintain the quality of industrial products, and they are considered to have low toxicity. However, recent evidence has suggested that parabens are toxic in mammalian cells, and parabens have been associated with allergic‐contact dermatitis, breast cancer and changes in testosterone levels. Sulforaphane, a cruciferous vegetable‐derived isothiocyanate, was effective in decreasing the growth inhibitory concentrations of ethyl‐, propyl‐, butyl‐ and methylparaben in the yeast Saccharomyces cerevisiae. The sulforaphane‐enhanced fungicidal effects of methylparaben were deemed to be caused by drastic cell membrane damage and the leakage of internal substances, such as nucleotides, from S. cerevisiae cells. Moreover sulforaphane markedly decreased the minimum concentration of methyl‐ and ethylparaben required to inhibit the growth of various microbes, such as the pathogenic yeast that causes severe mycosis, Candida albicans; the filamentous fungi Aspergillus niger; and the Gram‐negative bacterium Escherichia coli. Enhanced antimicrobial activity from the beneficial components of edible plants may increase paraben efficacy at low concentrations and minimize preservative‐induced side effects in consumers.
Significance and Impact of the Study
Sulforaphane, a natural and beneficial cruciferous vegetable‐derived isothiocyanate, increased the ability of parabens to disrupt fungal cell membranes. Paraben‐containing products have been reported to cause allergic contact dermatitis and drug hypersensitivity; therefore, methods to preserve organic products that may reduce the concentrations of parabens are both timely and necessary. In this study, we found that the combined antimicrobial effects of sulforaphane and parabens had the potential to reduce the paraben concentration needed to preserve organic products, thereby indicating that paraben toxicity may be reduced without affecting its activity as a preservative.
Significance and Impact of the Study: Sulforaphane, a natural and beneficial cruciferous vegetable‐derived isothiocyanate, increased the ability of parabens to disrupt fungal cell membranes. Paraben‐containing products have been reported to cause allergic contact dermatitis and drug hypersensitivity; therefore, methods to preserve organic products that may reduce the concentrations of parabens are both timely and necessary. In this study, we found that the combined antimicrobial effects of sulforaphane and parabens had the potential to reduce the paraben concentration needed to preserve organic products, thereby indicating that paraben toxicity may be reduced without affecting its activity as a preservative.
Abstract
In cuprate superconductors, the doping of carriers into the parent Mott insulator induces superconductivity and various other phases whose characteristic temperatures are typically plotted ...versus the doping level
p
. In most materials,
p
cannot be determined from the chemical composition, but it is derived from the superconducting transition temperature,
T
c
, using the assumption that the
T
c
dependence on doping is universal. Here, we present angle-resolved photoemission studies of Bi
2
Sr
2
CaCu
2
O
8+
δ
, cleaved and annealed in vacuum or in ozone to reduce or increase the doping from the initial value corresponding to
T
c
= 91 K. We show that
p
can be determined from the underlying Fermi surfaces and that in-situ annealing allows mapping of a wide doping regime, covering the superconducting dome and the non-superconducting phase on the overdoped side. Our results show a surprisingly smooth dependence of the inferred Fermi surface with doping. In the highly overdoped regime, the superconducting gap approaches the value of 2Δ
0
= (4 ± 1)
k
B
T
c
PDF
