The analysis of large-scale turbulence characteristics in the Indonesian seas derived from a regional model based on the Princeton Ocean Model

Turbulence characteristics in the Indonesian seas on the horizontal scale of order of 100 km were calculated with a regional model of the Indonesian seas circulation in the area based on the Princeton Ocean Model (POM). As is well known, the POM incorporates the Mellor–Yamada turbulence closure scheme. The calculated characteristics are: twice the turbulence kinetic energy per unit mass, <i>q</i>²; the turbulence master scale, &ell;; mixing coefficients of momentum, <i>K</i>_M; and temperature and salinity, <i>K</i>_H; etc. The analyzed turbulence has been generated essentially by the shear of large-scale ocean currents and by the large-scale wind turbulence. We focused on the analysis of turbulence around important topographic features, such as the Lifamatola Sill, the North Sangihe Ridge, the Dewakang Sill, and the North and South Halmahera Sea Sills. In general, the structure of turbulence characteristics in these regions turned out to be similar. For this reason, we have carried out a detailed analysis of the Lifamatola Sill region because dynamically this region is very important and some estimates of mixing coefficients in this area are available. <br><br> Briefly, the main results are as follows. The distribution of <i>q</i>² is quite adequately reproduced by the model. To the north of the Lifamatola Sill (in the Maluku Sea) and to the south of the Sill (in the Seram Sea), large values of <i>q</i>² occur in the deep layer extending several hundred meters above the bottom. The observed increase of <i>q</i>² near the very bottom is probably due to the increase of velocity shear and the corresponding shear production of <i>q</i>² very close to the bottom. The turbulence master scale, &ell;, was found to be constant in the main depth of the ocean, while &ell; rapidly decreases close to the bottom, as one would expect. However, in deep profiles away from the sill, the effect of topography results in the &ell; structure being unreasonably complicated as one moves towards the bottom. Values of 15 to 20 × 10^&minus;4 m² s^-1 were obtained for <i>K</i>_M and <i>K</i>_H in deep water in the vicinity of the Lifamatola Sill. These estimates agree well with basin-scale averaged values of 13.3 × 10^&minus;4 m² s^-1 found diagnostically for <i>K</i>_H in the deep Banda and Seram Seas (Gordon et al., 2003) and a value of 9.0 × 10^&minus;4 m² s^-1 found diagnostically for <i>K</i>_H for the deep Banda Sea system (van Aken et al., 1988). The somewhat higher simulated values can be explained by the presence of steep topography around the sill.

Vitamin D binding protein isoforms as candidate predictors of disease extension in childhood arthritis

Introduction: Juvenile idiopathic arthritis (JIA) comprises a poorly understood group of chronic autoimmune diseases with variable clinical outcomes. We investigated whether the synovial fluid (SF) proteome could distinguish a subset of patients in whom disease extends to affect a large number of joints.

Methods: SF samples from 57 patients were obtained around time of initial diagnosis of JIA, labeled with Cy dyes and separated by two-dimensional electrophoresis. Multivariate analyses were used to isolate a panel of proteins which distinguish patient subgroups. Proteins were identified using MALDI-TOF mass spectrometry with expression verified by immunochemical methods. Protein glycosylation status was confirmed by hydrophilic interaction liquid chromatography.

Results: A truncated isoform of vitamin D binding protein (VDBP) is present at significantly reduced levels in the SF of oligoarticular patients at risk of disease extension, relative to other subgroups (p < 0.05). Furthermore, sialylated forms of immunopurified synovial VDBP were significantly reduced in extended oligoarticular patients (p < 0.005).

Conclusion: Reduced conversion of VDBP to a macrophage activation factor may be used to stratify patients to determine risk of disease extension in JIA patients.

V3 versican isoform alters the behavior of human melanoma cells by interfering with CD44/ErbB-dependent signaling

Versican is a hyaluronan-binding, extracellular chondroitin sulfate proteoglycan produced by several tumor types, including malignant melanoma, which exists as four different splice variants. The short V3 isoform contains the G1 and G3 terminal domains of versican that may potentially interact directly or indirectly with the hyaluronan receptor CD44 and the EGFR, respectively. We have previously described that overexpression of V3 in MeWo human melanoma cells markedly reduces tumor cell growth in vitro and in vivo. In this study we have investigated the signaling mechanism of V3 by silencing the expression of CD44 in control and V3-expressing melanoma cells. Suppression of CD44 had the same effects on cell proliferation and cell migration than those provoked by V3 expression, suggesting that V3 acts through a CD44-mediated mechanism. Furthermore, CD44-dependent hyaluronan internalization was blocked by V3 expression and CD44 silencing, leading to an accumulation of this glycosaminoglycan in the pericellular matrix and to changes in cell migration on hyaluronan. Furthermore, ERK1/2 and p38 activation after EGF treatment were decreased in V3-expressing cells suggesting that V3 may also interact with the EGFR through its G3 domain. The existence of a EGFR/ErbB2 receptor complex able to interact with CD44 was identified in MeWo melanoma cells. V3 overexpression resulted in a reduced interaction between EGFR/ErbB2 and CD44 in response to EGF treatment. Our results indicate that the V3 isoform of versican interferes with CD44 and the CD44-EGFR/ErbB2 interaction, altering the signaling pathways, such as ERK1/2 and p38 MAPK, that regulate cell proliferation and migration.

Characterisation of the frequent exacerbator phenotype in COPD patients in a large UK primary care population

BACKGROUND: The 'frequent exacerbator' is recognised as an important phenotype in COPD. Current understanding about this phenotype comes from prospective longitudinal clinical trials in secondary/tertiary care with little information reported in primary care populations.

AIMS: To characterize the frequent-exacerbator phenotype and identify associated risk factors in a large UK primary care COPD population.

METHODS: Using a large database of primary care patients from 80 UK general practices, patients were categorised using GOLD 2014 criteria into high and low risk groups based on exacerbation history. A multivariate logistic regression model was used to investigate covariates associated with the frequent-exacerbator phenotype and risk of experiencing a severe exacerbation (leading to hospitalisation).

RESULTS: Of the total study population (n = 9219), 2612 (28%) fulfilled the criteria for high risk frequent-exacerbators. Independent risk factors (adjusted odds ratio [95% CI]) for ≥2 exacerbations were: most severely impaired modified Medical Research Council (mMRC) dyspnoea score (mMRC grade 4: 4.37 [2.64-7.23]), lower FEV1 percent predicted (FEV1 <30%: 2.42 [1.61-3.65]), co-morbid cardiovascular disease (1.42 [1.19-1.68]), depression (1.56 [1.22-1.99]) or osteoporosis (1.54 [1.19-2.01]), and female gender (1.20 [1.01-1.43]). Older patients (≥75 years), those with most severe lung impairment (FEV1 <30%), those with highest mMRC score and those with co-morbid osteoporosis were identified as most at risk of experiencing exacerbations requiring hospitalisation.

CONCLUSIONS: Although COPD exacerbations occur across all grades of disease severity, female patients with high dyspnoea scores, more severely impaired lung function and co-morbidities are at greatest risk. Elderly patients, with severely impaired lung function, high mMRC scores and osteoporosis are associated with experience of severe exacerbations requiring hospitalisation.

Glycosylation of Vitamin D Binding Protein Reduced in Juvenile Idiopathic Arthritis Patients At Risk of Disease Extension.

Background/Purpose:Juvenile idiopathic arthritis (JIA) comprises a poorly understood group of chronic, childhood onset, autoimmune diseases with variable clinical outcomes. We investigated whether profiling of the synovial fluid (SF) proteome by a fluorescent dye based, two-dimensional gel (DIGE) approach could distinguish the subset of patients in whom inflammation extends to affect a large number of joints, early in the disease process. The post-translational modifications to candidate protein markers were verified by a novel deglycosylation strategy.Methods:SF samples from 57 patients were obtained around time of initial diagnosis of JIA. At 1 year from inclusion patients were categorized according to ILAR criteria as oligoarticular arthritis (n=26), extended oligoarticular (n=8) and polyarticular disease (n=18). SF samples were labeled with Cy dyes and separated by two-dimensional electrophoresis. Multivariate analyses were used to isolate a panel of proteins which distinguish patient subgroups. Proteins were identified using MALDI-TOF mass spectrometry with vitamin D binding protein (VDBP) expression and siaylation further verified by immunohistochemistry, ELISA test and immunoprecipitation. Candidate biomarkers were compared to conventional inflammation measure C-reactive protein (CRP). Sialic acid residues were enzymatically cleaved from immunopurified SF VDBP, enriched by hydrophilic interaction liquid chromatography (HILIC) and analysed by mass spectrometry.Results:Hierarchical clustering based on the expression levels of a set of 23 proteins segregated the extended-to-be oligoarticular from the oligoarticular patients. A cleaved isoform of VDBP, spot 873, is present at significantly reduced levels in the SF of oligoarticular patients at risk of disease extension, relative to other subgroups (p<0.05). Conversely total levels of vitamin D binding protein are elevated in plasma and ROC curves indicate an improved diagnostic sensitivity to detect patients at risk of disease extension, over both spot 873 and CRP levels. Sialysed forms of intact immunopurified VDBP were more prevalent in persistent oligoarticular patient synovial fluids.Conclusion:The data indicate that a subset of the synovial fluid proteome may be used to stratify patients to determine risk of disease extension. Reduced conversion of VDBP to a macrophage activation factor may represent a novel pathway contributing to increased risk of disease extension in JIA patients.

Infrared and Raman screening of seized novel psychoactive substances: A large scale study of >200 samples

The potential of IR absorption and Raman spectroscopy for rapid identification of novel psychoactive substances (NPS) has been tested using a set of 221 unsorted seized samples suspected of containing NPS. Both IR and Raman spectra showed large variation between the different sub-classifications of NPS and smaller, but still distinguishable, differences between closely related compounds within the same class. In initial tests, screening the samples using spectral searching against a limited reference library allowed only 41% of the samples to be fully identified. The limiting factor in the identification was the large number of active compounds in the seized samples for which no reference vibrational data were available in the libraries rather than poor spectral quality. Therefore, when 33 of these compounds were independently identified by NMR and mass spectrometry and their spectra used to extend the libraries, the percentage of samples identified by IR and Raman screening alone increased to 76%, with only 7% of samples having no identifiable constituents. This study, which is the largest of its type ever carried out, therefore demonstrates that this approach of detecting non-matching samples and then identifying them using standard analytical methods has considerable potential in NPS screening since it allows rapid identification of the constituents of the majority of street quality samples. Only one complete feedback cycle was carried out in this study but there is clearly the potential to carry out continuous identification/updating when this system is used in operational settings.

PP1 interactomes as a means of characterizing protein functions

A maioria das funções celulares, incluindo expressão de genes, crescimento e proliferação celulares, metabolismo, morfologia, motilidade, comunicação intercelular e apoptose, é regulada por interações proteína-proteína (IPP). A célula responde a uma variedade de estímulos, como tal a expressão de proteínas é um processo dinâmico e os complexos formados são constituídos transitoriamente mudando de acordo com o seu ciclo funcional, adicionalmente, muitas proteínas são expressas de uma forma dependente do tipo de célula. Em qualquer instante a célula pode conter cerca de centenas de milhares de IPPs binárias, e encontrar os companheiros de interação de uma proteína é um meio de inferir a sua função. Alterações em redes de IPP podem também fornecer informações acerca de mecanismos de doença. O método de identificação binário mais frequentemente usado é o sistema Dois Hibrido de Levedura, adaptado para rastreio em larga escala. Esta metodologia foi aqui usada para identificar os interactomas específicos de isoforma da Proteína Fosfatase 1 (PP1), em cérebro humano. A PP1 é uma proteína fosfatase de Ser/Thr envolvida numa grande variedade de vias e eventos celulares. É uma proteína conservada codificada por três genes, que originam as isoformas α, β, e γ, com a última a originar γ1 e γ2 por splicing alternativo. As diferentes isoformas da PP1 são reguladas pelos companheiros de interação – proteínas que interagem com a PP1 (PIPs). A natureza modular dos complexos da PP1, bem como a sua associação combinacional, gera um largo reportório de complexos reguladores e papéis em circuitos de sinalização celular. Os interactomas da PP1 específicos de isofoma, em cérebro, foram aqui descritos, com um total de 263 interações identificadas e integradas com os dados recolhidos de várias bases de dados de IPPs. Adicionalmente, duas PIPs foram selecionadas para uma caracterização mais aprofundada da interação: Taperina e Sinfilina-1A. A Taperina é uma proteína ainda pouco descrita, descoberta recentemente como sendo uma PIP. A sua interação com as diferentes isoformas da PP1 e localização celulares foram analisadas. Foi descoberto que a Taperina é clivada e que está presente no citoplasma, membrana e núcleo e que aumenta os níveis de PP1, em células HeLa. Na membrana ela co-localiza com a PP1 e a actina e uma forma mutada da Taperina, no motivo de ligação à PP1, está enriquecida no núcleo, juntamente com a actina. Mais, foi descoberto que a Taperina é expressa em testículo e localiza-se na região acrossómica da cabeça do espermatozoide, uma estrutura onde a PP1 e a actina estão também presentes. A Sinfilina-1A, uma isoforma da Sinfilina-1, é uma proteína com tendência para agregar e tóxica, envolvida na doença de Parkinson. Foi mostrado que a Sinfilina-1A liga às isoformas da PP1, por co-transformação em levedura, e que mutação do seu motivo de ligação à PP1 diminuiu significativamente a interação, num ensaio de overlay. Quando sobre-expressa em células Cos-7, a Sinfilina-1A formou corpos de inclusão onde a PP1 estava presente, no entanto a forma mutada da Sinfilina-1A também foi capaz de agregar, indicando que a formação de inclusões não foi dependente de ligação à PP1. Este trabalho dá uma nova perspetiva dos interactomas da PP1, incluindo a identificação de dezenas de companheiros de ligação específicos de isoforma, e enfatiza a importância das PIPs, não apenas na compreensão das funções celulares da PP1 mas também, como alvos de intervenção terapêutica.

Dynamical behaviour of multi-particle large-scale systems

Collective behaviours can be observed in both natural and man-made systems composed of a large number of elemental subsystems. Typically, each elemental subsystem has its own dynamics but, whenever interaction between individuals occurs, the individual behaviours tend to be relaxed, and collective behaviours emerge. In this paper, the collective behaviour of a large-scale system composed of several coupled elemental particles is analysed. The dynamics of the particles are governed by the same type of equations but having different parameter values and initial conditions. Coupling between particles is based on statistical feedback, which means that each particle is affected by the average behaviour of its neighbours. It is shown that the global system may unveil several types of collective behaviours, corresponding to partial synchronisation, characterised by the existence of several clusters of synchronised subsystems, and global synchronisation between particles, where all the elemental particles synchronise completely.

Optimization in the Technological Steps for the Fabrication of Large Area Micromirror Arrays

Micromirror arrays are a very strong candidate for future energy saving applications. Within this work, the fabrication process for these micromirror arrays has been optimized and some steps for the large area fabrication of micromirror modules were performed. At first the surface roughness of the insulation layer of silicon dioxide (SiO2) was investigated. This SiO2 thin layer was deposited on three different type of substrates i.e. silicon, glass and Polyethylene Naphthalate (PEN) substrates. The deposition techniques which has been used are Plasma Enhanced Chemical Vapor Deposition (PECVD), Physical Vapor Deposition (PVD) and Ion Beam Sputter Deposition (IBSD). The thickness of the SiO2 thin layer was kept constant at 150nm for each deposition process. The surface roughness was measured by Stylus Profilometry and Atomic Force Microscopy (AFM). It was found that the layer which was deposited by IBSD has got the minimum surface roughness value and the layer which was deposited by PECVD process has the highest surface roughness value. During the same investigation, the substrate temperature of PECVD was varied from 80° C to 300° C with the step size of 40° C and it was found that the surface roughness keeps on increasing as the substrate holder temperature increases in the PECVD process. A new insulation layer system was proposed to minimize the dielectric breakdown effect in insulation layer for micromirror arrays. The conventional bilayer system was replaced by five layer system but the total thickness of insulation layer remains the same. It was found that during the actuation of micromirror arrays structure, the dielectric breakdown effect was reduced considerably as compared to the bilayer system. In the second step the fabrication process of the micromirror arrays was successfully adapted and transferred from glass substrates to the flexible PEN substrates by optimizing the conventional process recipe. In the last section, a large module of micromirror arrays was fabricated by electrically interconnecting four 10cm×10cm micromirror modules on a glass pane having dimensions of 21cm×21cm.

Use of Large Clear-Cuts by Wilson’s Warbler in an Eastern Canadian Boreal Forest

Wilson’s Warbler (Cardellina pusilla; WIWA) has been declining for several decades, possibly because of habitat loss. We compared occupancy of territorial males in two habitat types of Québec’s boreal forest, alder (Alnus spp.) scrubland and recent clear-cuts. Singing males occurred in clusters, their occupancy was similar in both habitats, but increased with the amount of alder or clear-cut within 400 m of point-count stations. A despotic distribution of males between habitats appeared unlikely, because there were no differences in morphology between males captured in clear-cuts vs. alder. Those results contrast with the prevailing view, mostly based on western populations, that WIWA are wetland or riparian specialists, and provide the first evidence for a preference for large tracts of habitat in this species. Clear-cuts in the boreal forest may benefit WIWA by supplying alternative nesting habitat. However, the role of clear-cuts as source or sink habitats needs to be addressed with data on reproduction.

The effect of a large freshwater perturbation on the glacial north Atlantic Ocean using a coupled general circulation model

The commonly held view of the conditions in the North Atlantic at the last glacial maximum, based on the interpretation of proxy records, is of large-scale cooling compared to today, limited deep convection, and extensive sea ice, all associated with a southward displaced and weakened overturning thermohaline circulation (THC) in the North Atlantic. Not all studies support that view; in particular, the "strength of the overturning circulation" is contentious and is a quantity that is difficult to determine even for the present day. Quasi-equilibrium simulations with coupled climate models forced by glacial boundary conditions have produced differing results, as have inferences made from proxy records. Most studies suggest the weaker circulation, some suggest little or no change, and a few suggest a stronger circulation. Here results are presented from a three-dimensional climate model, the Hadley Centre Coupled Model version 3 (HadCM3), of the coupled atmosphere - ocean - sea ice system suggesting, in a qualitative sense, that these diverging views could all have occurred at different times during the last glacial period, with different modes existing at different times. One mode might have been characterized by an active THC associated with moderate temperatures in the North Atlantic and a modest expanse of sea ice. The other mode, perhaps forced by large inputs of meltwater from the continental ice sheets into the northern North Atlantic, might have been characterized by a sluggish THC associated with very cold conditions around the North Atlantic and a large areal cover of sea ice. The authors' model simulation of such a mode, forced by a large input of freshwater, bears several of the characteristics of the Climate: Long-range Investigation, Mapping, and Prediction (CLIMAP) Project's reconstruction of glacial sea surface temperature and sea ice extent.

The climatic effects of the direct injection of water vapour into the stratosphere by large volcanic eruptions

We describe a novel mechanism that can significantly lower the amplitude of the climatic response to certain large volcanic eruptions and examine its impact with a coupled ocean-atmosphere climate model. If sufficiently large amounts of water vapour enter the stratosphere, a climatically significant amount of water vapour can be left over in the lower stratosphere after the eruption, even after sulphate aerosol formation. This excess stratospheric humidity warms the tropospheric climate, and acts to balance the climatic cooling induced by the volcanic aerosol, especially because the humidity anomaly lasts for a period that is longer than the residence time of aerosol in the stratosphere. In particular, northern hemisphere high latitude cooling is reduced in magnitude. We discuss this mechanism in the context of the discrepancy between the observed and modelled cooling following the Krakatau eruption in 1883. We hypothesize that moist coignimbrite plumes caused by pyroclastic flows travelling over ocean rather than land, resulting from an eruption close enough to the ocean, might provide the additional source of stratospheric water vapour.

Phylogenomics of eukaryotes: Impact of missing data on large alignments

Resolving the relationships between Metazoa and other eukaryotic groups as well as between metazoan phyla is central to the understanding of the origin and evolution of animals. The current view is based on limited data sets, either a single gene with many species (e.g., ribosomal RNA) or many genes but with only a few species. Because a reliable phylogenetic inference simultaneously requires numerous genes and numerous species, we assembled a very large data set containing 129 orthologous proteins (similar to30,000 aligned amino acid positions) for 36 eukaryotic species. Included in the alignments are data from the choanoflagellate Monosiga ovata, obtained through the sequencing of about 1,000 cDNAs. We provide conclusive support for choanoflagellates as the closest relative of animals and for fungi as the second closest. The monophyly of Plantae and chromalveolates was recovered but without strong statistical support. Within animals, in contrast to the monophyly of Coelomata observed in several recent large-scale analyses, we recovered a paraphyletic Coelamata, with nematodes and platyhelminths nested within. To include a diverse sample of organisms, data from EST projects were used for several species, resulting in a large amount of missing data in our alignment (about 25%). By using different approaches, we verify that the inferred phylogeny is not sensitive to these missing data. Therefore, this large data set provides a reliable phylogenetic framework for studying eukaryotic and animal evolution and will be easily extendable when large amounts of sequence information become available from a broader taxonomic range.

Comparison of predictions of baking volume using large deformation rheological properties

Three large deformation rheological tests, the Kieffer dough extensibility system, the D/R dough inflation system and the 2 g mixograph test, were carried out on doughs made from a large number of winter wheat lines and cultivars grown in Poland. These lines and cultivars represented a broad spread in baking performance in order to assess their suitability as predictors of baking volume. The parameters most closely associated with baking volume were strain hardening index, bubble failure strain, and mixograph bandwidth at 10min. Simple correlations with baking volume indicate that bubble failure strain and strain hardening index give the highest correlations, whilst the use of best subsets regression, which selects the best combination of parameters, gave increased correlations with R-2 = 0.865 for dough inflation parameters, R-2 = 0. 842 for Kieffer parameters and R-2 = 0.760 for mixograph parameters. (c) 2007 Elsevier Ltd. All rights reserved.

The impact of price promotions on producer strategies in markets with large product heterogeneity

Although current research indicates that increasing the number of options has negative effects on the cognitive ability of consumers, little understanding has been given to the consequences on producers and their strategic behavior. This article tests whether a large portfolio of products is beneficial to producers by observing UK consumer response to price promotions. The article shows that discounts induce mainly segment switching (74% of the total impact), with a limited effect on stockpiling (26%) and no impact on purchase incidence. Consequently, consumers prefer to “follow the discount” rather than purchase multiple units of the same wine. This result seems to explain the current structure of the market, and suggests that discounts may conflict with segment loyalty, a situation that disfavors producers, particularly in very populated segments. Results also casts doubts on the economic sustainability of competition based on an intense product differentiation in the wine sector.