bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of soluble surfactants on dynamic wetting of flexible substrates: A finite element study
Authors: Madasu Srinath
Published: December 2009

Dynamic wetting plays an important role in coating processes. This paper presents a finite element study of the effect of surfactants under the sorption-controlled regime on the location of the dynamic contact line for flexible solids at steady state. The bulk concentration of the surfactant is assumed to be in excess such that the bulk phase diffusion is neglected and the surface equation of state based on the Frumkin adsorption framework is used to predict the distribution of surface tension as a function of surface surfactant concentration. The finite element model solves for the fluid-structural interactions between an elastic solid and a viscous liquid along with the surfactant distribution at the liquid/vapor free surface. To predict the shape of the free surface, the model uses arbitrary Lagrangian Eulerian mesh motion in both fluid and solid phases. The variation in dynamic contact line position with respect to various parameters such as downstream pressure, Peclet number, surfactant elasticity number, Biot number, interaction parameter, and initial surface coverage are presented for the finite element model. It can be concluded that the presence of surfactant has a significant effect on the location of the dynamic contact line for flexible solids at steady state and the stability of the liquid-vapor free surface.
Nonlinear current-voltage behavior and giant positive magnetoresistance in nonmagnetic Au/Yttria-stabilized zirconia/Si heterostructures
Authors: Qu T. L. , Li J. , Zhao Y. G. , Mei J. W. , Liu X. , Tian H. F. , Shi J. P. , Guo S. M. , Li J. , Zheng D. N. , Li J. Q.
Published: December 2009

We report on the nonlinear current-voltage (I-V) behavior and giant positive magnetoresistance (GPMR) in the Au/Yttria-stabilized zirconia/Si heterostructures. The I-V curves of the heterostructures show a rectifying property and follow the Fowler–Nordheim tunneling behavior for the larger forward bias voltages. The GPMR of the samples increases with decreasing temperature and exceeds 100 000% in a magnetic field of 7 T at 20 K with a voltage of +4 V. It also shows anisotropy with magnetoresistance for the magnetic field perpendicular to the current larger than that of the parallel case. A possible mechanism was proposed to account for the results.
An electrohydrodynamic flow in ac electrowetting
Authors: Lee Horim , Yun Sungchan , Ko Sung Hee , Kang Kwan Hyoung
Published: December 2009

In ac electrowetting, hydrodynamic flows occur within a droplet. Two distinct flow patterns were observed, depending on the frequency of the applied electrical signal. The flow at low-frequency range was explained in terms of shape oscillation and a steady streaming process in conjunction with contact line oscillation. The origin of the flow at high-frequency range has not yet been explained. We suggest that the high-frequency flow originated mainly from the electrothermal effect, in which electrical charge is generated due to the gradient of electrical conductivity and permittivity, which is induced by the Joule heating of fluid medium. To support our argument, we analyzed the flow field numerically while considering the electrical body force generated by the electrothermal effect. We visualized the flow pattern and measured the flow velocity inside the droplet. The numerical results show qualitative agreement with experimental results with respect to electric field and frequency dependence of flow velocity. The effects of induced-charge electro-osmosis, natural convection, and the Marangoni flow are discussed.
Mapping the Dirac point in gated bilayer graphene
Authors: Deshpande A. , Bao W. , Zhao Z. , Lau C. N. , LeRoy B. J.
Published: December 2009

We have performed low temperature scanning tunneling spectroscopy measurements on exfoliated bilayer graphene on SiO2. By varying the back gate voltage we observed a linear shift of the Dirac point and an opening of a bandgap due to the perpendicular electric field. In addition to observing a shift in the Dirac point, we also measured its spatial dependence using spatially resolved scanning tunneling spectroscopy. The spatial variation of the Dirac point was not correlated with topographic features and therefore we attribute its shift to random charged impurities.
Modelling the possible effects of climate change on an Australian multi-fleet prawn fishery
Authors: Ives M. C. , Scandol J. P. , Montgomery S. S. , Suthers I. M.
Published: December 2009

The relationship between fisheries and climate has been given renewed emphasis owing to increasing concern regarding anthropogenically induced climate change. This relationship is particularly important for estuarine fisheries, where there are documented correlations between river discharge and productivity. The commercial catch of school prawns (Metapenaeus macleayi) has been shown to be positively correlated with the rates of river discharge in northern New South Wales, Australia. In the present study, a simulation model was developed to analyse the dynamics of the stock for 10 years under alternative river discharge scenarios, and the effectiveness of a series of management strategies under these scenarios was examined. A size-based metapopulation model was developed that incorporated the dynamics of school prawn populations in three habitats being harvested by three different fishing methods. The model indicated that both the growth and movement of prawns were affected by the rates of river discharge, and that higher rates of river discharge usually generated increased commercial catches, but this outcome was not certain. It was concluded that the population does not appear to be overexploited and that none of the three alternative management strategies performed better within the model than the current spatio-temporal closures, even under a wide range of river discharge scenarios.
Partitioning of underwater direct and diffuse ultraviolet irradiance in a shallow water coral reef
Authors: Veal Cameron J. , Michael Kelvin J. , Nunez Manuel
Published: December 2009

In optically shallow waters of coral reefs, the contribution of both direct and diffuse ultraviolet irradiance is poorly documented yet its involvement in biological processes is highly significant. Here we present a new approach of partitioning the ultraviolet attenuation coefficient into direct and diffuse components in the top 5 m of waters surrounding Heron Reef, Queensland, Australia (23°27′S, 151°55′E), during the austral summer solstice from 11 to 21 December 2005. A commercial ultraviolet radiometer, which operated in selected spectral bands centred at 305, 313, 320, 340, 380 and 395 nm, was fitted with an aquatic shadow-band that allowed the measurement of both global and diffuse irradiances. Direct irradiance was estimated by subtracting diffuse irradiance from global irradiance. Results revealed that direct irradiance was attenuated more quickly than diffuse irradiance, with stronger attenuation in the shorter wavelengths. Attenuation coefficients for the global, diffuse and direct components of irradiance were significantly different, justifying their separate treatment through partitioning. A significant dependence on turbidity explained more than 70% of the variation in attenuation of ultraviolet irradiance at the shorter wavelengths. The direct ultraviolet irradiance can exceed 50% of the global ultraviolet irradiance in shallow waters (0–5 m), a significant result that is generally overlooked in optical and biological studies.
Impacts of spatial scales of fisheries and environmental data on catch per unit effort standardisation
Authors: Tian Siquan , Chen Yong , Chen Xinjun , Xu Liuxiong , Dai Xiaojie
Published: December 2009

Spatial scale is an important factor that needs to be considered in data collection and analysis in ecological studies. Studies focusing on the quantitative evaluation of impacts of spatial scales are, however, limited in fisheries. Using the Chinese squid-jigging fishery in the north-western Pacific Ocean as an example, we evaluated impacts of spatial scale used in grouping fisheries and environmental data on the standardisation of fisheries catch per unit effort (CPUE). We developed 18 scenarios of different spatial scales with a combination of three latitudinal levels (0.5°, 1° and 2°) and six longitudinal levels (0.5°, 1°, 2°, 3°, 4° and 5°) to aggregate the data. We then applied generalised additive models to analyse the 18 scenarios of data for the CPUE standardisation, and quantified differences among the scenarios. This study shows that longitudinal and latitudinal spatial scale and size of the spatial area for data aggregation can greatly influence the standardisation of CPUE. We recommend that similar studies be undertaken whenever possible to evaluate the roles of spatial scales and to identify the optimal spatial scale for data aggregations in the standardisation of CPUE and fisheries stock assessment.
Ecology of the rare microbial biosphere of the Arctic Ocean
Authors: Galand Pierre E. , Casamayor Emilio O. , Kirchman David L. , Lovejoy Connie
Published: December 2009

Understanding the role of microbes in the oceans has focused on taxa that occur in high abundance; yet most of the marine microbial diversity is largely determined by a long tail of low-abundance taxa. This rare biosphere may have a cosmopolitan distribution because of high dispersal and low loss rates, and possibly represents a source of phylotypes that become abundant when environmental conditions change. However, the true ecological role of rare marine microorganisms is still not known. Here, we use pyrosequencing to describe the structure and composition of the rare biosphere and to test whether it represents cosmopolitan taxa or whether, similar to abundant phylotypes, the rare community has a biogeography. Our examination of 740,353 16S rRNA gene sequences from 32 bacterial and archaeal communities from various locations of the Arctic Ocean showed that rare phylotypes did not have a cosmopolitan distribution but, rather, followed patterns similar to those of the most abundant members of the community and of the entire community. The abundance distributions of rare and abundant phylotypes were different, following a log-series and log-normal model, respectively, and the taxonomic composition of the rare biosphere was similar to the composition of the abundant phylotypes. We conclude that the rare biosphere has a biogeography and that its tremendous diversity is most likely subjected to ecological processes such as selection, speciation, and extinction.
Spontaneous formation of the unlocked state of the ribosome is a multistep process
Authors: Munro James B. , Altman Roger B. , Tung Chang-Shung , Cate Jamie H. D. , Sanbonmatsu Kevin Y. , Blanchard Scott C.
Published: December 2009

The mechanism of substrate translocation through the ribosome is central to the rapid and faithful translation of mRNA into proteins. The rate-limiting step in translocation is an unlocking process that includes the formation of an “unlocked” intermediate state, which requires the convergence of large-scale conformational events within the ribosome including tRNA hybrid states formation, closure of the ribosomal L1 stalk domain, and subunit ratcheting. Here, by imaging of the pretranslocation ribosome complex from multiple structural perspectives using two- and three-color single-molecule fluorescence resonance energy transfer, we observe that tRNA hybrid states formation and L1 stalk closure, events central to the unlocking mechanism, are not tightly coupled. These findings reveal that the unlocked state is achieved through a stochastic-multistep process, where the extent of conformational coupling depends on the nature of tRNA substrates. These data suggest that cellular mechanisms affecting the coupling of conformational processes on the ribosome may regulate the process of translation elongation.
High-resolution protein complexes from integrating genomic information with molecular simulation
Authors: Schug Alexander , Weigt Martin , Onuchic José N. , Hwa Terence , Szurmant Hendrik
Published: December 2009

Bacteria use two-component signal transduction systems (TCS) extensively to sense and react to external stimuli. In these, a membrane-bound sensor histidine kinase (SK) autophosphorylates in response to an environmental stimulus and transfers the phosphoryl group to a transcription factor/response regulator (RR) that mediates the cellular response. The complex between these two proteins is ruled by transient interactions, which provides a challenge to experimental structure determination techniques. The functional and structural homolog of an SK/RR pair Spo0B/Spo0F, however, has been structurally resolved. Here, we describe a method capable of generating structural models of such transient protein complexes. By using existing structures of the individual proteins, our method combines bioinformatically derived contact residue information with molecular dynamics simulations. We find crystal resolution accuracy with existing crystallographic data when reconstituting the known system Spo0B/Spo0F. Using this approach, we introduce a complex structure of TM0853/TM0468 as an exemplary SK/RR TCS, consistent with all experimentally available data.
Ancient DNA reveals late survival of mammoth and horse in interior Alaska
Authors: Haile James , Froese Duane G. , MacPhee Ross D. E. , Roberts Richard G. , Arnold Lee J. , Reyes Alberto V. , Rasmussen Morten , Nielsen Rasmus , Brook Barry W. , Robinson Simon , Demuro Martina , Gilbert M. Thomas P. , Munch Kasper , Austin Jeremy J. , Cooper Alan , Barnes Ian , Möller Per , Willerslev Eske
Published: December 2009

Causes of late Quaternary extinctions of large mammals (“megafauna”) continue to be debated, especially for continental losses, because spatial and temporal patterns of extinction are poorly known. Accurate latest appearance dates (LADs) for such taxa are critical for interpreting the process of extinction. The extinction of woolly mammoth and horse in northwestern North America is currently placed at 15,000–13,000 calendar years before present (yr BP), based on LADs from dating surveys of macrofossils (bones and teeth). Advantages of using macrofossils to estimate when a species became extinct are offset, however, by the improbability of finding and dating the remains of the last-surviving members of populations that were restricted in numbers or confined to refugia. Here we report an alternative approach to detect ‘ghost ranges’ of dwindling populations, based on recovery of ancient DNA from perennially frozen and securely dated sediments (
sed
aDNA). In such contexts,
sed
aDNA can reveal the molecular presence of species that appear absent in the macrofossil record. We show that woolly mammoth and horse persisted in interior Alaska until at least 10,500 yr BP, several thousands of years later than indicated from macrofossil surveys. These results contradict claims that Holocene survival of mammoths in Beringia was restricted to ecologically isolated high-latitude islands. More importantly, our finding that mammoth and horse overlapped with humans for several millennia in the region where people initially entered the Americas challenges theories that megafaunal extinction occurred within centuries of human arrival or were due to an extraterrestrial impact in the late Pleistocene.
Autocatalysis and organocatalysis with synthetic structures
Authors: Kamioka Seiji , Ajami Dariush , Rebek Julius
Published: December 2009

The discovery of ribozymes led to the proposal of an RNA world, where a single type of molecule was supposedly capable of self-replication and chemical catalysis. We show here that both autocatalysis and organocatalysis can be engineered into a synthetic structure. The compound is shown to selectively accelerate its own formation and catalyze either hydrogenation or nucleophilic addition to α,β-unsaturated aldehydes. The observed reactivity indicates that the components of a purported pre-RNA world conceivably include smaller organic molecules.
Sloshed and sentenced: A prevalence study of alcohol use disorders among offenders in the North East of England
Authors: Newbury‐Birch Dorothy , Harrison Barbara , Brown Nicola , Kaner Eileen
Published: December 2009

The annual cost of alcohol‐related harm in the UK is estimated to be between £17.7 and £25.1 billion with healthcare costs alone reaching £2.7 billion and the costs of alcohol‐fuelled crime and disorder accounting for £7.3 billion each year. The aim of the study was to examine the prevalence of alcohol use disorders (AUD) in prison and probation settings in the North East of England, and to compare the ability of the Alcohol Use Disorders Identification Test (AUDIT) and Offender Assessment System (OASys) at identifying alcohol‐related need in probation clients. A quantitative prevalence study was carried out using anonymous questionnaires with participants from four prisons and three probation offices in the North East who voluntarily completed the AUDIT questionnaire during a 1‐month period in 2006. Response outcomes on AUDIT were compared with OASys scores which identify alcohol‐related need in probation. At the time of the study OASys scores were not available for
offenders in prison. Seven hundred and fifteen questionnaires were completed. Sixty‐three per cent of men and 57% of women were identified as having an AUD with over a third of all individuals scoring within the possibly dependant range (20+ on AUDIT). Around 40% of probation cases who were classified as either hazardous, harmful or possibly dependant drinkers on AUDIT were not identified by OASys. The results indicate that the prevalence of AUD in offenders is much higher than in the general population. In addition, current methods of identifying offenders with alcohol‐related need in probation are flawed and as many such people go undetected. Alcohol assessment procedures need to be improved in criminal justice setting order to correctly identify people with AUD.
The state of health care provision and extent of mental health in the prisons of the Arab world: A literature review and commentary
Authors: Gharaibeh Numan , El‐Khoury Joseph
Published: December 2009

Relevant literature was searched using MEDLINE, PsycINFO and Google in addition to Arabic search engines for information. Due to the shortage of scholarly articles on the subject, we broadened our search to publications from human rights organisation and articles in the mainstream press. We estimated the total carceral population in the member countries of the Arab league at 338,500 prisoners, over 46,000 of whom could be suffering from severe mental illness. We relied on indirect indicators of mental health services such as the quality of medical care in general, accounts of prison conditions by prisoners and their families, and the abundant literature on human rights abuses. Despite a grim overall picture, we highlight signs of improvement in recent years. Psychiatrists working in Arabic prisons face a number of challenges.We comment on directions for the future in the field of correctional psychiatry in the Arab countries including from the perspective of research.
Myrica rubra Extracts Protect the Liver from CCl4‐Induced Damage
Authors: Xu Lizhi , Gao Jing , Wang Yucai , Yu Wen , Zhao Xiaoning , Yang Xiaohe , Zhong Zengtao , Qian Zhong-Ming
Published: December 2009

The relationship between the expression of mitochondrial voltage‐dependent anion channels (VDACs) and the protective effects of Myrica rubra Sieb. Et Zucc fruit extract (MCE) against carbon tetrachloride (CCl4)‐induced liver damage was investigated. Pretreatment with 50 mg kg−1, 150 mg kg−1 or 450 mg kg−1 MCE significantly blocked the CCl4‐induced increase in both serum aspartate aminotransferase (sAST) and serum alanine aminotransferase (sALT) levels in mice (P < .05 or .01 versus CCl4 group). Ultrastructural observations of decreased nuclear condensation, ameliorated mitochondrial fragmentation of the cristae and less lipid deposition by an electron microscope confirmed the hepatoprotection. The mitochondrial membrane potential dropped from −191.94 ± 8.84 mV to −132.06 ± 12.26 mV (P < .01) after the mice had been treated with CCl4. MCE attenuated CCl4‐induced mitochondrial membrane potential dissipation in a dose‐dependent manner. At a dose of 150 or 450 mg kg−1 of MCE, the mitochondrial membrane potentials were restored (P < .05). Pretreatment with MCE also prevented the elevation of intra‐mitochondrial free calcium as observed in the liver of the CCl4‐insulted mice (P < .01 versus CCl4 group). In addition, MCE treatment (50–450 mg kg−1) significantly increased both transcription and translation of VDAC inhibited by CCl4. The above data suggest that MCE mitigates the damage to liver mitochondria induced by CCl4, possibly through the regulation of mitochondrial VDAC, one of the most important proteins in the mitochondrial outer membrane.
MEF2 transcriptional activity maintains mitochondrial adaptation in cardiac pressure overload
Authors: el Azzouzi Hamid , van Oort Ralph J. , van der Nagel Roel , Sluiter Wim , Bergmann Martin W. , De Windt Leon J.
Published: December 2009

Aims

The transcription factor MEF2 is a downstream target for several hypertrophic signalling pathways in the heart, suggesting that MEF2 may act as a valuable therapeutic target in the treatment of heart failure.

Methods and results

In this study, we investigated the potential benefits of overall MEF2 inhibition in a mouse model of chronic pressure overloading, by subjecting transgenic mice expressing a dominant negative form of MEF2 (DN‐MEF2 Tg) in the heart, to transverse aortic constriction (TAC). Histological analysis revealed no major differences in cardiac remodelling between DN‐MEF2 Tg and control mice after TAC. Surprisingly, echocardiographic analysis revealed that DN‐MEF2 Tg mice had a decrease in cardiac function compared with control animals. Analysis of the mitochondrial respiratory chain showed that DN‐MEF2 Tg mice displayed lower expression of NADH dehydrogenase subunit 6 (ND6), part of mitochondrial Complex I. The reduced expression of ND6 in DN‐MEF2 Tg mice after pressure overload correlated with an increase in cell death secondary to overproduction of reactive oxygen species (ROS).

Conclusion

Our data suggest that MEF2 transcriptional activity is required for mitochondrial function and its inhibition predisposes the heart to impaired mitochondrial function, overproduction of ROS, enhanced cell death, and cardiac dysfunction, following pressure overload.
Caveat medicus! Pulmonary hypertension in the elderly: a word of caution
Authors: Boilson Barry A. , Schirger John A. , Borlaug Barry A.
Published: December 2009

Heart failure with preserved ejection fraction (HFpEF) is a common but under‐recognized cause of pulmonary hypertension (PH), particularly among the elderly. While elevated pulmonary artery pressures are clearly associated with increased mortality in HFpEF, it remains unknown whether or how pulmonary vascular disease in HFpEF should be treated. This case emphasizes the importance of maintaining a high index of suspicion for HFpEF in elderly patients presenting with PH and illustrates potential hazards associated with selective pulmonary vasodilation in this growing population.
Estimating gear efficiency in a combined acoustic and trawl survey, with reference to the spatial distribution of demersal fish
Authors: Doray Mathieu , Mahévas Stéphanie , Trenkel Verena M.
Published: December 2009

Doray, M., Mahévas, S., and Trenkel, V. M. 2010. Estimating gear efficiency in a combined acoustic and trawl survey, with reference to the spatial distribution of demersal fish. – ICES Journal of Marine Science, 67: 668–676. Few analyses have been performed to estimate the efficiency of trawls targeting demersal fish using the ratio of catches and acoustic densities. In summer 2006, acoustic and fishing data were collected simultaneously over 3 d by three fishing vessels equipped with identical pelagic trawls in the Bay of Biscay. Variography identified moderate spatial autocorrelation in the acoustic backscatter at a mean scale of 3 km, a scale slightly smaller than the mean haul length (3.5 km), indicating that fish horizontal availability did not influence trawl efficiency. Acoustic backscattering densities expressed as nautical area scattering coefficients (NASCs) recorded in the trawled layer were compared with equivalent NASC (ENASC) values calculated from the species composition in the trawl, fish-length structure, and available relationships between target strength and fish length. Estimates of trawl efficiency for hake-dominated trawls were computed as the slopes of the relationships ENASC = 0.008 NASC and ENASC = 0.18 NASC0.31 for trawls made by day and night, respectively. For the whole demersal community, the relationships were ENASC = 0.022 NASC and ENASC = 0.17 NASC0.33 for trawls made by day and night, respectively.
Fluctuations in phenotypes and genotypes within populations of Pseudomonasaeruginosa in the cystic fibrosis lung during pulmonary exacerbations
Authors: Fothergill Joanne L. , Mowat Eilidh , Ledson Martin J. , Walshaw Martin J. , Winstanley Craig
Published: December 2009

Chronic respiratory infection by Pseudomonas aeruginosa contributessignificantly to the morbidity and mortality associated with cystic fibrosis (CF).Using a series of phenotypic and genotypic tests on collections of 40 isolatesper sputum sample, we analysed fluctuations within sputum populations of the P. aeruginosa Liverpool epidemic strain (LES) during pulmonaryexacerbations. For each of three patients, three sequential sputum sampleswere analysed: (1) on presentation with exacerbation at the RegionalAdult Cystic Fibrosis Unit, Liverpool; (2) a few days into intravenousantibiotic treatment; (3) when the patient had recovered. Fluctuationswere observed in morphotype distribution, the production of virulence-associatedquorum-sensing-dependent exoproducts (the phenazine compound pyocyaninand the elastase LasA), antibiotic susceptibility profiles and levelsof auxotrophy. PCR assays were used to screen isolates for the presence ofnovel regions of the LES genome (islands and prophages) and to detectfree phages. In one patient there was an increase in the prevalence of theLESGI-5 genomic island during the sampling period from 10 to 97.5 %carriage. LES phages 2–4 were detected in either the majority or allsputum samples tested, indicating widespread phage activity during the samplingperiod. The results of this study are indicative that significant fluctuationsoccur within P. aeruginosa populations during short periods of pulmonaryexacerbation and intravenous antibiotic therapy.
Genetic adaptation of Pseudomonas aeruginosa during chronic lung infection of patients with cystic fibrosis: strong and weak mutators with heterogeneous genetic backgrounds emerge in mucA and/or lasR mutants
Authors: Ciofu Oana , Mandsberg Lotte F. , Bjarnsholt Thomas , Wassermann Tina , Høiby Niels
Published: December 2009

During the chronic lung infection of patients with cystic fibrosis (CF),Pseudomonas aeruginosacan survive for long periods due to adaptive evolution mediated by genetic variation. Hypermutability is considered to play an important role in this adaptive evolution and it has been demonstrated that mutator populations are amplified in the CF lung by hitchhiking with adaptive mutations. Two of the genes that are frequently mutated in isolates from chronic infection aremucAandlasR. Loss-of-function mutations in these genes determine the phenotypic switch to mucoidy and loss of quorum sensing, which are considered hallmarks of chronic virulence. The aims of our study were to investigate (1) the genetic background of theP. aeruginosasubpopulations with non-mutator, weak or strong mutator phenotype and their dynamics during the chronic lung infection, and (2) the time sequence in which the hypermutable, mucoid and quorum-sensing-negative phenotypes emerge during chronic lung infection. For these purposes the sequences ofmutS,mutL,uvrD,mutT,mutYandmutManti-mutator genes as well as ofmucAandlasRwere analysed in 70 sequentialP. aeruginosaisolates obtained from the respiratory secretions of 10 CF patients (one to three isolates per time point). Analysis of the genetic background of the mutator phenotype showed thatmutSwas the most commonly affected gene followed bymutLin isolates with strong mutator phenotype. ThemutT,mutY,mutMgenes were affected in isolates with low fold-changes in the mutation frequencies compared to the reference strain PAO1. Isolates with non-mutator, weak or strong mutator phenotype were represented at all time points showing co-existence of these subpopulations, which suggests parallel evolution of the various mutators in the different focal niches of infection in the CF lung. Mutations inmucAandlasRoccurred earlier than mutations in the anti-mutator genes, showing that hypermutability is not a prerequisite for the acquisition of mucoidy and loss of quorum sensing, considered hallmarks of chronic virulence. Significantly higher mutation rates and MICs of ceftazidime, meropenem and ciprofloxacin were found for isolates collected late (more than 10 years) during the chronic lung infection compared to isolates collected earlier, which suggests an amplification of the mutator subpopulation by hitchhiking with development of antibiotic resistance. Similar evolutionary pathways concordant with adaptive radiation were observed in different clonal lineages ofP. aeruginosafrom CF patients.
De novo assembly of human genomes with massively parallel short read sequencing
Authors: Li Ruiqiang , Zhu Hongmei , Ruan Jue , Qian Wubin , Fang Xiaodong , Shi Zhongbin , Li Yingrui , Li Shengting , Shan Gao , Kristiansen Karsten , Li Songgang , Yang Huanming , Wang Jian , Wang Jun
Published: December 2009

Next-generation massively parallel DNA sequencing technologies provide ultrahigh throughput at a substantially lower unit data cost; however, the data are very short read length sequences, making de novo assembly extremely challenging. Here, we describe a novel method for de novo assembly of large genomes from short read sequences. We successfully assembled both the Asian and African human genome sequences, achieving an N50 contig size of 7.4 and 5.9 kilobases (kb) and scaffold of 446.3 and 61.9 kb, respectively. The development of this de novo short read assembly method creates new opportunities for building reference sequences and carrying out accurate analyses of unexplored genomes in a cost-effective way.
Anaesthesia for proximal femoral fracture in the UK: first report from the NHS Hip Fracture Anaesthesia Network*
Authors: White S. M. , Griffiths R. , Holloway J. , Shannon A.
Published: December 2009

The aim of this audit was to investigate process, personnel and anaesthetic factors in relation to mortality among patients with proximal femoral fractures. A questionnaire was used to record standardised data about 1195 patients with proximal femoral fracture admitted to 22 hospitals contributing to the Hip Fracture Anaesthesia Network over a 2‐month winter period. Patients were demographically similar between hospitals (mean age 81 years, 73% female, median ASA grade 3). However, there was wide variation in time from admission to operation (24–108 h) and 30‐day postoperative mortality (2–25%). Fifty percent of hospitals had a mean admission to operation time < 48 h. Forty‐two percent of operations were delayed: 51% for organisational; 44% for medical; and 4% for ‘anaesthetic’ reasons. Regional anaesthesia was administered to 49% of patients (by hospital, range = 0–82%), 51% received general anaesthesia and 19% of patients received peripheral nerve blockade. Consultants administered 61% of anaesthetics (17–100%). Wide national variations in current management of patients sustaining proximal femoral fracture reflect a lack of research evidence on which to base best practice guidance. Collaborative audits such as this provide a robust method of collecting such evidence.
The cardiac calsequestrin gene (CASQ2) is up‐regulated in the thyroid in patients with Graves’ ophthalmopathy – support for a role of autoimmunity against calsequestrin as the triggering event
Authors: Wescombe Leon , Lahooti Hooshang , Gopinath Bamini , Wall Jack R.
Published: December 2009

Background  Graves’ Ophthalmopathy (GO) is a complex eye and orbital disorder that is uniquely linked to Graves’ Hyperthyroidism (GH) and has traditionally been considered a cross‐reactive immune response against the thyroid stimulating hormone receptor (TSHR) in orbital tissue. However, because there is no direct evidence, such as specific TSHR antibodies or T lymphocytes targeting the orbital tissues in patients with GO compared to those without eye disease, it is important to consider alternative hypotheses for the pathogenesis of GO. The aim of this study was to identify differentially expressed genes within the thyroid of patients with GO and GH as a possible explanation for a thyroid initiated orbital autoimmunity.

Methods  RNA was extracted from thyroid glands of patients with GO (n = 10) and GH (n = 8) post‐total thyroidectomy. RNA samples were arrayed on Illumina® Human Ref‐8 Expression BeadChips™ representing 20 589 genes. Microarray results of selected genes were validated by quantitative PCR (qPCR) and levels of protein translation measured by Western blot analysis.

Findings  Two hundred and nighty‐five genes were differentially expressed between patients with GO and GH. Of these, the cardiac calsequestrin gene (CASQ2) was the most highly expressed gene in GO (2·2‐fold increase, P < 0·05). The succinate dehydrogenase flavoprotein subunit gene (SDHA) was also significantly up‐regulated in GO (P < 0·05), 1·4‐fold, while genes encoding the thyroid antigens thyroglobulin, thyroid peroxidase and TSHR were not differentially expressed. qPCR verified up‐regulation of CASQ2 and down‐regulation BMP7, CD80, IGFBP5, and MYD88 genes in GO. Western blot analysis showed that the average CASQ/GAPDH protein expression ratios for GH and GO were 1·04 and 1·03, respectively. t‐Test analysis of data generated a P‐value of 0·26, therefore no significant difference was found for CASQ protein expression in thyroid tissue between GH and GO.

Interpretation  The skeletal and cardiac calsequestrin proteins share 68·4% amino acid homology. Previous work has shown that RNA levels of skeletal muscle calsequestrin are 4·7 times higher in extraocular muscle (EOM) than in masticatory skeletal muscle (jaw), and cardiac calsequestrin is expressed 2·7 times more in EOM. We postulate that up‐regulation of casq2 gene in the thyroid of patients with GH may lead to the production of autoantibodies and sensitized T‐lymphocytes, which cross‐react with calsequestrin in the EOM of patients who develop ophthalmopathy.
The 4‐mg intravenous dexamethasone suppression test in the diagnosis of Cushing’s syndrome
Authors: Jung Caroline , Alford Frank P. , Topliss Duncan J. , Burgess John R. , Long Fiona , Gome James J. , Stockigt Jim R. , Inder Warrick J.
Published: December 2009

Objective  Optimal diagnostic criteria for the 4‐mg intravenous dexamethasone suppression test (IVDST) in patients with Cushing’s syndrome (CS), compared with normal subjects, have not been established. We evaluated the performance of the 4‐mg IVDST for differentiating CS from normal subjects and to define the responses in CS of various aetiologies.

Design, subjects, measurements  Thirty‐two control subjects [normal and overweight/obese participants with or without type 2 diabetes) were prospectively studied, and data from 66 patients with Cushing’s disease (CD), three with ectopic ACTH syndrome (EAS), 14 with adrenal Cushing’s (AC)] and 15 with low probability of CS (LPC) from three tertiary hospitals were retrospectively evaluated. Dexamethasone was infused at 1 mg/h for 4 h. Plasma cortisol and ACTH were measured at −60 min (baseline), −5 min, +3 h, +4 h, +5 h and at +23 and +23·5 h on Day 2.

Results  Control subjects (including those with type 2 diabetes) exhibited a marked suppression of cortisol which was maintained until Day 2. Two of 15 patients with LPC had Day 2 cortisol results that overlapped with CS. Patients with CD demonstrated partial suppression, with rebound hypercortisolism on Day 2. Patients with AC and EAS did not suppress cortisol levels. Day 2 cortisol level of >130 nmol/l (or >20% of the baseline) diagnosed CS with 100% sensitivity and 96% specificity.

Conclusion  While the IVDST allowed complete discrimination between control subjects and CS, 13% of LPC overlapped with CS. Given the small number of EAS, no conclusion can be drawn regarding the utility of this test in the differential diagnosis of CS.
Predictive value of pentagastrin test for preoperative differential diagnosis between C‐cell hyperplasia and medullary thyroid carcinoma in patients with moderately elevated basal calcitonin levels
Authors: Milone F. , Ramundo V. , Chiofalo M. G. , Severino R. , Paciolla I. , Pezzullo L. , Lombardi G. , Colao A. , Faggiano A.
Published: December 2009

Background and Objectives  Medullary thyroid carcinoma (MTC) is a calcitonin (CT)‐secreting neuroendocrine tumour originating from thyroid C cells. Serum CT concentrations are helpful in the early detection of MTC, while it is still unclear whether they can be used also for the differential diagnosis between MTC and C‐cell hyperplasia (CCH), a precancerous condition in familial MTCs but with unclear clinical significance in sporadic MTCs. Nowadays, surgery is recommended in all patients with basal or pentagastrin (PG)‐stimulated CT value of 100 pg/ml or more, without discriminating if they are affected with MTC or CCH only. The objective of this study was to investigate the utility of the PG test for CT in distinguishing CCH from MTC before surgery.

Patients and Methods  Sixteen of 20 patients with thyroid nodules and basal CT levels between 15 and 100 ng/l had a positive PG test (>100 ng/l PG CT peak) and form the basis of the data analysis. A diagnosis of MTC was histologically proved on surgical samples in seven patients and of CCH in nine other patients. Four patients with neither FNAB nor PG test consistent with a diagnosis of MTC did not undergo thyroidectomy.

Results  A peak of CT of 275 ng/l after PG was able to significantly distinguish patients with MTC from patients with CCH, with 100% sensitivity and 89% specificity (P = 0·002). PG‐stimulated calcitonin levels >275 ng/l had a positive predictive value (PPV) value for diagnosis of MTC of 100%, and PG‐stimulated calcitonin levels <275 had a PPV for the diagnosis of CCH of 89%.

Conclusions  A CT cut‐off after PG of 275 ng/l is suggested to be highly predictive in distinguishing CCH from MTC before surgery, and this may be helpful in selecting patients for thyroid surgery.
A catalogue of reporting guidelines for health research
Authors: Simera I. , Moher D. , Hoey J. , Schulz K. F. , Altman D. G.
Published: December 2009

Eur J Clin Invest 2010; 40 (1): 35–53

Growing evidence demonstrates widespread deficiencies in the reporting of health research studies. The EQUATOR Network is an international initiative that aims to enhance the reliability and value of the published health research literature. EQUATOR provides resources, education and training to facilitate good research reporting and assists in the development, dissemination and implementation of robust reporting guidelines. This paper presents a collection of tools and guidelines available on the EQUATOR website (http://www.equator‐network.org) that have been developed to increase the accuracy and transparency of health research reporting.
Surface morphology of unalloyed steels remelted with intense plasma pulses
Authors: SARTOWSKA B. , PIEKOSZEWSKI J. , WALIŚ L. , BARLAK M.
Published: December 2009

The set of unalloyed steels with various carbon concentrations were irradiated with intense plasma pulses with following process parameters: energy density 5 J cm−2, pulse duration 2 μs, argon or nitrogen atmosphere. The energy density of each pulse was high enough to melt the surface layer of material. The cooling rate was estimated for 108 K s−1 using the modelling method which takes into account heat evolution in the iron sample. Samples were characterized using the scanning electron microscopy technique for remelted surface morphology investigations. The tests with profilometer allowed us to investigate the changes of roughness of the surface layers.
Microstructure and mechanical properties of AA7039+20%SiCw composite
Authors: BLAZ L. , KULA A. , KANEKO J. , SUGAMATA M. , WLOCH G. , SOBOTA K.
Published: December 2009

Hot deformation tests were performed on an AA7039‐matrix composite reinforced with a 20% addition of SiC whiskers. The flow stress maximum was reduced with deformation temperature from 640 MPa to ∼8 MPa at 293 K and 823 K, respectively. TEM observations, performed on as deformed samples, revealed a highly recovered substructure of the matrix and a striated structure of the whiskers. The fringes, which are perpendicular to the whiskers’ longitudinal axis, were ascribed to nano‐sized twins and stacking faults formed during the crystal growth rather than to some effects of the deformation process.
Tyrosinase gene (TYR) mutations in Chinese patients with oculocutaneous albinism type 1
Authors: Liu Jing , Choy Kwong‐Wai , Chan Leo WL , Leung Tak‐Yeung , Tam Pancy OS , Chiang Sylvia WY , Lam Dennis SC , Pang Chi‐Pui , Lai Timothy YY
Published: December 2009

Abstract

Background:  To identify the sequence variants of the tyrosinase (TYR) gene in Chinese families with oculocutaneous albinism.

Methods:  Three families with oculocutaneous albinism type 1 and 95 unrelated healthy Chinese individuals with normal pigmentation were screened for mutations in the TYR gene by direct sequencing. Computational algorithms were used to characterize the biological significance of the mutants.

Results:  Four previously reported mutations (R299C, R299H, W400L and frame‐shift c.930insC) and one novel mutation (F214del) were identified, and probands had homozygous or compound heterozygous TYR mutant alleles. None of the mutants were identified among the 95 normal control subjects. Computational analysis predicted that the R299C mutant inactivates the tyrosinase enzyme by misfolding of protein tertiary structure and/or retention of the misfolded tyrosinase within the endoplasmic reticulum, and F214del causes dysfunction of tyrosine enzyme by affecting the copper binding sites and altering substrate orientation and electronic transfers during catalytic reactions for melanosynthesis.

Conclusion:  We have identified five different TYR mutations, including one novel mutation, which caused oculocutaneous albinism type 1 in Chinese. Further analysis of the patients will be useful to determine the effects of these mutations on the tyrosinase activities.
From ‘cryptic species’ to integrative taxonomy: an iterative process involving DNA sequences, morphology, and behaviour leads to the resurrection of Sepsis pyrrhosoma (Sepsidae: Diptera)
Authors: Tan Denise S. H. , Ang Yuchen , Lim Gwynne S. , Ismail Mirza Rifqi Bin , Meier Rudolf
Published: December 2009

Tan, D. S. H., Ang, Y., Lim, G. S., Ismail, M. R. B. & Meier, R. (2010). From ‘cryptic species’ to integrative taxonomy: an iterative process involving DNA sequences, morphology, and behaviour leads to the resurrection of Sepsis pyrrhosoma (Sepsidae: Diptera). —Zoologica Scripta, 39, 51–61.

The increased availability of DNA sequences has led to a surge of ‘cryptic species’ in the literature. These units are usually proposed based on finding genetically distinct lineages within species that were initially defined based on morphological characters. However, few authors attempt to confirm whether these ‘cryptic’ units are species and even fewer authors are explicit about which species concept is applied. Here, we use an example from Sepsidae (Diptera) to demonstrate how cryptic species can be validated by an iterative process involving several data sources and an evaluation of the data under different species concepts. A phylogeographic analysis based on 50 specimens for five species of the flavimana group revealed deep mitochondrial splits within Sepsis flavimana which was suggestive of a cryptic species. We resolve the initial conflict between DNA sequences and morphology by adding new morphological data as well as behavioural evidence and tests for reproductive isolation. One cryptic species is confirmed and Sepsis pyrrhosoma, a former synonym of S. flavimana, is here shown to be a valid species under most species concepts. We can thus document that the same data can lead to similar conclusions under conflicting concepts once different kinds of data are integrated.
Interactions between inducible nitric oxide synthase and cyclooxygenase‐2 in response to ischaemia‐reperfusion of rabbit bladder
Authors: Masuda Hitoshi , Kawano Keizo , Matsuoka Yoh , Yokoyama Minato , Koga Fumitaka , Saito Kazutaka , Kihara Kazunori , Azuma Hiroshi
Published: December 2009

OBJECTIVE

To investigate the interactions between inducible nitric oxide synthase (iNOS) and cyclooxygenase‐2 (COX‐2) in response to ischaemia‐reperfusion (I/R) of rabbit bladder.

MATERIALS AND METHODS

Rabbit bladders were exposed to 2 h of ischaemia by bilaterally clamping the major arteries entering the bladder and then a subsequent 36 h of reperfusion (I/R) with or without intraperitoneal administration of a selective iNOS inhibitor n‐(3‐(amynomethyl)benzyl)acetamidine (1400W) or a selective COX‐2 inhibitor NS‐398 given 1 h before killing. The bladder tissues were processed for isometric tension experiments, enzymatic NOS activitiy, tissue contents of nitrite/nitrate (NOX), cyclic guanosine monophosphate (cGMP) and COX activity determined by prostaglandin E2 (PGE2) production.

RESULTS

iNOS and constitutive NOS (cNOS) activities, NOX and PGE2 contents in the bladder tissues at 36 h after reperfusion were significantly higher than those in the sham group with no significant increase in cGMP. Treatment with 1400W abrogated the increases in iNOS activity and NOX as well as PGE2 without changing cNOS activity. In the tension experiments, a NOS substrate, l‐arginine, induced detrusor contraction only in the I/R group, which was inhibited by 1400W or NS‐398 but not by a selective soluble guanylate cyclase inhibitor 1H‐[1,2,4] oxadiazole[4,3‐a]quinoxalin‐1‐one (ODQ). 8‐Br‐cGMP induced detrusor relaxation in the sham and I/R groups. Also, l‐arginine increased NOX and PGE2 in the bladder tissues only in the I/R group, which were inhibited by pretreatment with 1400W. While, l‐arginine increased cGMP contents in the I/R group and this increase was suppressed by ODQ but not by 1400W.

CONCLUSION

These results show that NO derived from an up‐regulation of iNOS after I/R increases COX‐2‐derived PG via a cGMP‐independent mechanism. NO‐mediated activation of COX‐2 may be an important mechanism for the modulation of bladder function after I/R injury.
Glucose‐regulated protein 78 expression in urothelial carcinoma of the upper urinary tract
Authors: Uematsu Kenji , Ogata Sho , Nakanishi Kuniaki , Hiroi Sadayuki , Tominaga Susumu , Aida Shinsuke , Kawai Toshiaki
Published: December 2009

OBJECTIVE

To examine glucose‐regulated protein 78 (GRP78; a major molecular chaperone at the endoplasmic reticulum, strongly expressed in several tumours) expression in urothelial carcinoma (UC) of the upper urinary tract (UUT) and to evaluate the diagnostic and progressive importance of GRP78 expression in UC‐UUT.

PATIENTS AND METHODS

We investigated GRP78 expression (using immunohistochemistry) in 126 UC‐UUTs to assess its relevance to progression. GRP78 overexpression was recognised in 23 (18.3%) of tumour samples.

RESULTS

There was no association between GRP78 overexpression and clinicopathological findings, except for an association with low grade in invasive tumours. GRP78 overexpression significantly improved the disease‐free survival rate in all patients (according to univariate and multivariate analyses), but did not alter the overall survival rate.

CONCLUSION

The detection of GRP78 overexpression would appear to provide valuable information for the prognosis of UC‐UUT.