2,125 research outputs found
Optical carrier wave shocking: detection and dispersion
Carrier wave shocking is studied using the Pseudo-Spectral Spatial Domain
(PSSD) technique. We describe the shock detection diagnostics necessary for
this numerical study, and verify them against theoretical shocking predictions
for the dispersionless case. These predictions show Carrier Envelope Phase
(CEP) and pulse bandwidth sensitivity in the single-cycle regime. The flexible
dispersion management offered by PSSD enables us to independently control the
linear and nonlinear dispersion. Customized dispersion profiles allow us to
analyze the development of both carrier self-steepening and shocks. The results
exhibit a marked asymmetry between normal and anomalous dispersion, both in the
limits of the shocking regime and in the (near) shocked pulse waveforms.
Combining these insights, we offer some suggestions on how carrier shocking (or
at least extreme self-steepening) might be realised experimentally.Comment: 9 page
Associations between socioeconomic status and environmental toxicant concentrations in adults in the USA: NHANES 2001-2010
This is the final version, also available from Elsevier via the DOI in this record.Low level chronic exposure to toxicants is associated with a range of adverse health effects. Understanding the various factors that influence the chemical burden of an individual is of critical importance to public health strategies. We investigated the relationships between socioeconomic status (SES) and bio-monitored chemical concentration in five cross-sectional waves of the U.S. National Health and Nutrition Examination Survey (NHANES).We utilised adjusted linear regression models to investigate the association between 179 toxicants and the poverty income ratio (PIR) for five NHANES waves. We then selected a subset of chemicals associated with PIR in 3 or more NHANES waves and investigated potential mediating factors using structural equation modelling.PIR was associated with 18 chemicals in 3 or more NHANES waves. Higher SES individuals had higher burdens of serum and urinary mercury, arsenic, caesium, thallium, perfluorooctanoic acid, perfluorononanoic acid, mono(carboxyoctyl) phthalate and benzophenone-3. Inverse associations were noted between PIR and serum and urinary lead and cadmium, antimony, bisphenol A and three phthalates (mono-benzyl, mono-isobutyl, mono-n-butyl). Key mediators included fish and shellfish consumption for the PIR, mercury, arsenic, thallium and perfluorononanoic acid associations. Sunscreen use was an important mediator in the benzophenone-3/PIR relationship. The association between PIR and cadmium or lead was partially mediated by smoking, occupation and diet.These results provide a comprehensive analysis of exposure patterns as a function of socioeconomic status in US adults, providing important information to guide future public health remediation measures to decrease toxicant and disease burdens within society. © 2013 Elsevier Ltd.University of ExeterEuropean Social Fund Convergence Programme for Cornwall and the Isles of ScillyEuropean Regional Development Fund Programme 2007 to 201
New Forces Influencing Savanna Conservation: Increasing Land Prices Driven by Gentrification and Speculation at the Landscape Scale
Land transformation reduces biodiversity and regional sustainability, with land price being an indicator of the opportunity cost to a landowner of resisting land conversion. However, reliable spatially explicit databases of current land prices are generally lacking in developing countries. We used tools from data science to scrape 1,487 georeferenced land prices in southern Kenya from the internet. Prices were higher for land near cities and in areas of high agricultural productivity, but also around the Maasai Mara National Reserve. Predicted land prices ranged from US4,618,805 per acre. Land speculation associated with expanding urbanization increases the opportunity and acquisition costs of maintaining conservation buffer zones, corridors, and dispersal areas. However, high land values are also found adjacent to a world-famous tourist destination. Profit-driven turnover of ownership, subdivision, and transformation of land is occurring at a rapid pace in southern Kenya, to the detriment of savanna biodiversity and the sustainability of the pastoral social–ecological system
Genes of the GadX-GadW Regulon in Escherichia coli
Acid in the stomach is thought to be a barrier to bacterial colonization of the intestine. Escherichia coli, however, has three systems for acid resistance, which overcome this barrier. The most effective of these systems is dependent on transport and decarboxylation of glutamate. GadX regulates two genes that encode isoforms of glutamate decarboxylase critical to this system, but additional genes associated with the glutamate-dependent acid resistance system remained to be identified. The gadX gene and a second downstream araC-like transcription factor gene, gadW, were mutated separately and in combination, and the gene expression profiles of the mutants were compared to those of the wild-type strain grown in neutral and acidified media under conditions favoring induction of glutamate-dependent acid resistance. Cluster and principal-component analyses identified 15 GadX-regulated, acid-inducible genes. Reverse transcriptase mapping demonstrated that these genes are organized in 10 operons. Analysis of the strain lacking GadX but possessing GadW confirmed that GadX is a transcriptional activator under acidic growth conditions. Analysis of the strain lacking GadW but possessing GadX indicated that GadW exerts negative control over three GadX target genes. The strain lacking both GadX and GadW was defective in acid induction of most but not all GadX target genes, consistent with the roles of GadW as an inhibitor of GadX-dependent activation of some genes and an activator of other genes. Resistance to acid was decreased under certain conditions in a gadX mutant and even more so by combined mutation of gadX and gadW. However, there was no defect in colonization of the streptomycin-treated mouse model by the gadX mutant in competition with the wild type, and the gadX gadW mutant was a better colonizer than the wild type. Thus, E. coli colonization of the mouse does not appear to require glutamate-dependent acid resistance
Biogeochemistry: Early phosphorus redigested
Atmospheric oxygen was maintained at low levels throughout huge swathes of Earth's early history. Estimates of phosphorus availability through time suggest that scavenging from anoxic, iron-rich oceans stabilized this low-oxygen world
Paroxysmal extreme pain disorder M1627K mutation in human Nav1.7 renders DRG neurons hyperexcitable
Background:
Paroxysmal extreme pain disorder (PEPD) is an autosomal dominant painful neuropathy with many, but not all, cases linked to gain-of-function mutations in SCN9A which encodes voltage-gated sodium channel Nav1.7. Severe pain episodes and skin flushing start in infancy and are induced by perianal probing or bowl movement, and pain progresses to ocular and mandibular areas with age. Carbamazepine has been effective in relieving symptoms, while other drugs including other anti-epileptics are less effective.
Results:
Sequencing of SCN9A coding exons from an English patient, diagnosed with PEPD, has identified a methionine 1627 to lysine (M1627K) substitution in the linker joining segments S4 and S5 in domain IV. We confirm that M1627K depolarizes the voltage-dependence of fast-inactivation without substantially altering activation or slow-inactivation, and inactivates from the open state with slower kinetics. We show here that M1627K does not alter development of closed-state inactivation, and that M1627K channels recover from fast-inactivation faster than wild type channels, and produce larger currents in response to a slow ramp stimulus. Using current-clamp recordings, we also show that the M1627K mutant channel reduces the threshold for single action potentials in DRG neurons and increases the number of action potentials in response to graded stimuli.
Conclusion:
M1627K mutation was previously identified in a sporadic case of PEPD from France, and we now report it in an English family. We confirm the initial characterization of mutant M1627K effect on fast-inactivation of Nav1.7 and extend the analysis to other gating properties of the channel. We also show that M1627K mutant channels render DRG neurons hyperexcitable. Our new data provide a link between altered channel biophysics and pain in PEPD patients
Application of functional genomics to the chimeric mouse model of HCV infection: optimization of microarray protocols and genomics analysis
BACKGROUND: Many model systems of human viral disease involve human-mouse chimeric tissue. One such system is the recently developed SCID-beige/Alb-uPA mouse model of hepatitis C virus (HCV) infection which involves a human-mouse chimeric liver. The use of functional genomics to study HCV infection in these chimeric tissues is complicated by the potential cross-hybridization of mouse mRNA on human oligonucleotide microarrays. To identify genes affected by mouse liver mRNA hybridization, mRNA from identical human liver samples labeled with either Cy3 or Cy5 was compared in the presence and absence of known amounts of mouse liver mRNA labeled in only one dye. RESULTS: The results indicate that hybridization of mouse mRNA to the corresponding human gene probe on Agilent Human 22 K oligonucleotide microarray does occur. The number of genes affected by such cross-hybridization was subsequently reduced to approximately 300 genes both by increasing the hybridization temperature and using liver samples which contain at least 80% human tissue. In addition, Real Time quantitative RT-PCR using human specific probes was shown to be a valid method to verify the expression level in human cells of known cross-hybridizing genes. CONCLUSION: The identification of genes affected by cross-hybridization of mouse liver RNA on human oligonucleotide microarrays makes it feasible to use functional genomics approaches to study the chimeric SCID-beige/Alb-uPA mouse model of HCV infection. This approach used to study cross-species hybridization on oligonucleotide microarrays can be adapted to other chimeric systems of viral disease to facilitate selective analysis of human gene expression
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