1,092 research outputs found
Development of basic theories and techniques for determining stresses in rotating turbine or compressor blades
A method for measuring in-plane displacement of a rotating structure by using two laser speckle photographs is described. From the displacement measurements one can calculate strains and stresses due to a centrifugal load. This technique involves making separate speckle photographs of a test model. One photograph is made with the model loaded (model is rotating); the second photograph is made with no load on the model (model is stationary). A sandwich is constructed from the two speckle photographs and data are recovered in a manner similar to that used with conventional speckle photography. The basic theory, experimental procedures of this method, and data analysis of a simple rotating specimen are described. In addition the measurement of in-plane surface displacement components of a deformed solid, and the application of the coupled laser speckle interferometry and boundary-integral solution technique to two dimensional elasticity problems are addressed
Differential transcription profiles inAedes aegyptidetoxification genes after temephos selection
The mosquito Aedes aegypti is the main vector of Dengue and Yellow Fever flaviviruses. The organophosphate insecticide temephos is a larvicide that is used globally to control Ae. aegypti populations; many of which have in turn evolved resistance. Target site alteration in the acetylcholine esterase of this species has not being identified. Instead, we tracked changes in transcription of metabolic detoxification genes using the Ae. aegypti ‘Detox Chip’ microarray during five generations of temephos selection. We selected for temephos resistance in three replicates in each of six collections, five from Mexico, and one from Peru. The response to selection was tracked in terms of lethal concentrations. Uniform upregulation was seen in the epsilon class glutathione-S-transferase (eGST) genes in strains from Mexico prior to laboratory selection, while eGSTs in the Iquitos Peru strain became upregulated after five generations of temephos selection. While expression of many carboxyl/cholinesterase esterase (CCE) genes increased with selection, no single esterase was consistently upregulated and this same pattern was noted in the cytochrome P450 monooxygenase (CYP) genes and in other genes involved in reduction or oxidation of xenobiotics. Bioassays using glutathione-S-transferase (GST), CCE and CYP inhibitors suggest that various CCEs instead of GSTs are the main metabolic mechanism conferring resistance to temephos. We show that temephos-selected strains show no cross resistance to permethrin and that genes associated with temephos selection are largely independent of those selected with permethrin in a previous study
Importance of Tree-and Species-Level Interactions with Wildfire, Climate, and Soils in Interior Alaska: Implications for Forest Change Under a Warming Climate
The boreal zone of Alaska is dominated by interactions between disturbances, vegetation, and soils. These interactions are likely to change in the future through increasing permafrost thaw, more frequent and intense wildfires, and vegetation change from drought and competition. We utilize an individual tree-based vegetation model, the University of Virginia Forest Model Enhanced (UVAFME), to estimate current and future forest conditions across sites within interior Alaska. We updated UVAFME for application within interior Alaska, including improved simulation of permafrost dynamics, litter decay, nutrient dynamics, fire mortality, and postfire regrowth. Following these updates, UVAFME output on species-specific biomass and stem density was comparable to inventory measurements at various forest types within interior Alaska. We then simulated forest response to climate change at specific inventory locations and across the Tanana Valley River Basin on a 2 × 2 km2 grid. We derived projected temperature and precipitation from a five-model average taken from the CMIP5 archive under the RCP 4.5 and 8.5 scenarios. Results suggest that climate change and the concomitant impacts on wildfire and permafrost dynamics will result in overall decreases in biomass (particularly for spruce (Picea spp.)) within the interior Tanana Valley, despite increases in quaking aspen (Populus tremuloides) biomass, and a resulting shift towards higher deciduous fraction. Simulation results also predict increases in biomass at cold, wet locations and at high elevations, and decreases in biomass in dry locations, under both moderate (RCP 4.5) and extreme (RCP 8.5) climate change scenarios. These simulations demonstrate that a highly detailed, species interactive model can be used across a large region within Alaska to investigate interactions between vegetation, climate, wildfire, and permafrost. The vegetation changes predicted here have the capacity to feed back to broader scale climate-forest interactions in the North American boreal forest, a region which contributes significantly to the global carbon and energy budgets
Schools and civil society : corporate or community governance
School improvement depends upon mediating the cultural conditions of learning as young people journey between their parochial worlds and the public world of cosmopolitan society. Governing bodies have a crucial role in including or diminishing the representation of different cultural traditions and in enabling or frustrating the expression of voice and deliberation of differences whose resolution is central to the mediation of and responsiveness to learning needs. A recent study of governing bodies in England and Wales argues that the trend to corporatising school governance will diminish the capacity of schools to learn how they can understand cultural traditions and accommodate them in their curricula and teaching strategies. A democratic, stakeholder model remains crucial to the effective practice of governing schools. By deliberating and reconciling social and cultural differences, governance constitutes the practices for mediating particular and cosmopolitan worlds and thus the conditions for engaging young people in their learning, as well as in the preparation for citizenship in civil society
Dynamics of insecticide resistance in malaria vectors in Benin: first evidence of the presence of L1014S kdr mutation in Anopheles gambiae from West Africa
<p>Abstract</p> <p>Background</p> <p>Insecticide resistance monitoring is essential to help national programmers to implement more effective and sustainable malaria control strategies in endemic countries. This study reported the spatial and seasonal variations of insecticide resistance in malaria vectors in Benin, West Africa.</p> <p>Methods</p> <p><it>Anopheles gambiae s.l </it>populations were collected from October 2008 to June 2010 in four sites selected on the basis of different use of insecticides and environment. WHO susceptibility tests were carried out to detect resistance to DDT, fenitrothion, bendiocarb, permethrin and deltamethrin. The synergist piperonyl butoxide was used to assess the role of non-target site mechanisms in pyrethroid resistance. <it>Anopheles gambiae </it>mosquitoes were identified to species and to molecular M and S forms using PCR techniques. Molecular and biochemical assays were carried out to determine <it>kdr </it>and <it>Ace.1<sup>R </sup></it>allelic frequencies and activity of the detoxification enzymes.</p> <p>Results</p> <p>Throughout the surveys very high levels of mortality to bendiocarb and fenitrothion were observed in <it>An. gambiae s.l</it>. populations. However, high frequencies of resistance to DDT and pyrethroids were seen in both M and S form of <it>An. gambiae s.s</it>. and <it>Anopheles arabiensis</it>. PBO increased the toxicity of permethrin and restored almost full susceptibility to deltamethrin. <it>Anopheles gambiae s.l</it>. mosquitoes from Cotonou and Malanville showed higher oxidase activity compared to the Kisumu susceptible strain in 2009, whereas the esterase activity was higher in the mosquitoes from Bohicon in both 2008 and 2009. A high frequency of <it>1014F kdr </it>allele was initially showed in <it>An. gambiae </it>from Cotonou and Tori-Bossito whereas it increased in mosquitoes from Bohicon and Malanville during the second year. For the first time the <it>L1014S kdr </it>mutation was found in <it>An. arabiensis </it>in Benin. The <it>ace.1<sup>R </sup></it>mutation was almost absent <it>in An. gambiae s.l</it>.</p> <p>Conclusion</p> <p>Pyrethroid and DDT resistance is widespread in malaria vector in Benin and both metabolic and target site resistance are implicated. Resistance was not correlated with a change of malaria species and/or molecular forms. The <it>1014S kdr </it>allele was first identified in wild population of <it>An. arabiensis </it>hence confirming the expansion of pyrethroid resistance alleles in Africa.</p
Revealing the density of encoded functions in a viral RNA
Nikesh Patel, et al, ‘Revealing the density of encoded functions in a viral RNA’, Proceedings of the National Academy of Sciences of the United States of America (PNAS), Vol. 112 (7): 2227-2232, February 2015, doi: http:dx.doi.org/10. 1073/pnas.1420812112. This article is freely available online through the PNAS open access option.We present direct experimental evidence that assembly of a single-stranded RNA virus occurs via a packaging signal-mediated mechanism. We show that the sequences of coat protein recognition motifs within multiple, dispersed, putative RNA packaging signals, as well as their relative spacing within a genomic fragment, act collectively to influence the fidelity and yield of capsid self-assembly in vitro. These experiments confirm that the selective advantages for viral yield and encapsidation specificity, predicted from previous modeling of packaging signal-mediated assembly, are found in Nature. Regions of the genome that act as packaging signals also function in translational and transcriptional enhancement, as well as directly coding for the coat protein, highlighting the density of encoded functions within the viral RNA. Assembly and gene expression are therefore direct molecular competitors for different functional folds of the same RNA sequence. The strongest packaging signal in the test fragment, encodes a region of the coat protein that undergoes a conformational change upon contact with packaging signals. A similar phenomenon occurs in other RNA viruses for which packaging signals are known. These contacts hint at an even deeper density of encoded functions in viral RNA, which if confirmed, would have profound consequences for the evolution of this class of pathogensPeer reviewedFinal Published versio
Field-Caught Permethrin-Resistant Anopheles gambiae Overexpress CYP6P3, a P450 That Metabolises Pyrethroids
Insects exposed to pesticides undergo strong natural selection and have developed various adaptive mechanisms to survive. Resistance to pyrethroid insecticides in the malaria vector Anopheles gambiae is receiving increasing attention because it threatens the sustainability of malaria vector control programs in sub-Saharan Africa. An understanding of the molecular mechanisms conferring pyrethroid resistance gives insight into the processes of evolution of adaptive traits and facilitates the development of simple monitoring tools and novel strategies to restore the efficacy of insecticides. For this purpose, it is essential to understand which mechanisms are important in wild mosquitoes. Here, our aim was to identify enzymes that may be important in metabolic resistance to pyrethroids by measuring gene expression for over 250 genes potentially involved in metabolic resistance in phenotyped individuals from a highly resistant, wild A. gambiae population from Ghana. A cytochrome P450, CYP6P3, was significantly overexpressed in the survivors, and we show that the translated enzyme metabolises both alpha-cyano and non–alpha-cyano pyrethroids. This is the first study to demonstrate the capacity of a P450 identified in wild A. gambiae to metabolise insecticides. The findings add to the understanding of the genetic basis of insecticide resistance in wild mosquito populations
Anopheles gambiae distribution and insecticide resistance in the cities of Douala and Yaoundé (Cameroon): influence of urban agriculture and pollution
Background: Urban malaria is becoming a major health priority across Africa. A study was undertaken to assess
the importance of urban pollution and agriculture practice on the distribution and susceptibility to insecticide of
malaria vectors in the two main cities in Cameroon.
Methods: Anopheline larval breeding sites were surveyed and water samples analysed monthly from October 2009 to December 2010. Parameters analysed included turbidity, pH, temperature, conductivity, sulfates, phosphates,nitrates, nitrites, ammonia, aluminium, alkalinity, iron, potassium, manganese, magnesium, magnesium hardness and total hardness. Characteristics of water bodies in urban areas were compared to rural areas and between urban sites. The level of susceptibility of Anopheles gambiae to 4% DDT, 0.75% permethrin, 0.05% deltamethrin, 0.1% bendiocarb and 5% malathion were compared between mosquitoes collected from polluted, non polluted and cultivated areas.
Results: A total of 1,546 breeding sites, 690 in Yaoundé and 856 in Douala, were sampled in the course of the study. Almost all measured parameters had a concentration of 2- to 100-fold higher in urban compare to rural breeding sites. No resistance to malathion was detected, but bendiocarb resistance was present in Yaounde. Very low mortality rates were observed following DDT or permethrin exposure, associated with high kdr frequencies. Mosquitoes collected in cultivated areas, exhibited the highest resistant levels. There was little difference in insecticide resistance or kdr allele frequency in mosquitoes collected from polluted versus non-polluted sites.
Conclusion: The data confirm high selection pressure on mosquitoes originating from urban areas and suggest urban agriculture rather than pollution as the major factor driving resistance to insecticide
Phase II study of SPI-77 (sterically stabilised liposomal cisplatin) in advanced non-small-cell lung cancer
To determine the efficacy and tolerability of SPI-77 (sterically stabilised liposomal cisplatin) at three dose levels in patients with advanced non-small-cell lung cancer (NSCLC). Patients had Stage IIIB or IV NSCLC and were chemo-naïve, and Eastern Oncology Cooperative Group 0–2. The first cohort received SPI-77 at 100 mg m−2, the second 200 mg m−2 and the final cohort 260 mg m−2. Patients had also pharmacokinetics and analysis of leucocyte platinum (Pt)-DNA adducts performed. Twenty-six patients were treated, with 22 patients being evaluable for response. Only one response occurred at the 200 mg m−2 dose level for an overall response rate of 4.5% (7.1% at ⩾200 mg m−2). No significant toxicity was noted including nephrotoxicity or ototoxicity aside from two patients with Grade 3 nausea. No routine antiemetics or hydration was used. The pharmacokinetic profile of SPI-77 was typical for a liposomally formulated drug, and the AUC appeared to be proportional to the dose of SPI-77. Plasma Pt levels and leucocyte DNA adduct levels did not appear to rise with successive doses. SPI-77 demonstrates only modest activity in patients with NSCLC
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