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Essential Step (essential + step)
Selected AbstractsClustering: An Essential Step from Diverging to ConvergingCREATIVITY AND INNOVATION MANAGEMENT, Issue 1 2007Marc Tassoul Within the context of new product development processes and the Creative Problem Solving (CPS) process, the authors have come to the view that clustering is to be seen as a separate step in the process of diverging and converging. Clustering is generally presented as part of the converging stages, and as such categorized as a selection technique, which in the authors' view does not do justice to this activity. It is about expanding knowledge, about connecting ideas, and connecting ideas to problem statements, functionalities, and values and consequences. It is about building a shared understanding, in other words about ,making sense', an essential creative activity in the development of concepts and, although different from a more freewheeling divergent phase, can be as creative and maybe even more so. Four kinds of clusterings are distinguished: object clustering, morphological clustering, functional clustering and gestalt clustering. Object clustering is mainly aimed at categorizing ideas into an overviewable set of groups of ideas. No special connections are being made, other then looking for similarities. Morphological clustering is used to split up a problem into subproblems after which the ideas generated are considered as subsolutions which can then be combined into concepts. Functional clustering is interesting when different approaches can be chosen to answer some question. It permits a more strategic choice to be made. Gestalt clustering is a more synthesis like approach, often with a more metaphoric and artistic stance. Collage is a good example of such clustering. General guidelines for clustering are: use a bottom-up process of emergence; postpone early rationalisations and verbalisations; start grouping ideas on the basis of feeling and intuition; and use metaphoric names to identify clusters. [source] An optimized whole blood method for flow cytometric measurement of ZAP-70 protein expression in chronic lymphocytic leukemiaCYTOMETRY, Issue 4 2006T. Vincent Shankey Abstract Background: ZAP-70 protein expression has been proposed as a marker for immunoglobulin heavy chain mutational status, which some studies have correlated with disease course in B-cell chronic lymphocytic leukemia (CLL). Studies published to date measuring levels of expression of ZAP-70 intracellular protein using flow cytometry have demonstrated poor performance, as defined by the difference in signal in known positive and negative lymphocyte populations. Methods: A recently published method (Chow S, Hedley DW, Grom P, Magari R, Jacobberger JW, Shankey TV, Cytometry A 2005;67:4,17) to measure intracellular phospho-epitopes was optimized using a design of experiments (DOE) approach to provide the best separation of ZAP-70 expression in positive T- or NK-cells as compared to negative B-cells in peripheral blood samples. A number of commercially available anti-ZAP-70 antibody-conjugates were screened using this methodology, and the antibody-conjugate showing the best performance was chosen to develop a four-color, five antibody assays to measure ZAP-70 levels in whole blood specimens. Results: Using the optimized fixation and permeabilization method, improvement in assay performance (signal-to-noise, S/N) was seen in most of the antibodies tested. The custom SBZAP conjugate gave the best S/N when used in conjunction with this optimized fixation /permeabilization method. In conjunction with carefully standardized instrument set-up protocols, we obtained both intra- and interlaboratory reproducibility in the analysis of ZAP-70 expression in whole blood samples from normal and CLL patients. Conclusions: The development of a sensitive, specific and highly reproducible ZAP-70 assay represents only the first essential step for any clinical assay. The universal implementation of a validated data analysis method and the establishment of methodology-based cutoff points for clinical outcomes must next be established before ZAP-70 protein analysis can be routinely implemented in the clinical laboratory. © 2006 International Society for Analytical Cytology [source] Proteome analysis of the culture environment supporting undifferentiated mouse embryonic stem and germ cell growthELECTROPHORESIS, Issue 10 2007Nicolas Buhr Abstract The therapeutical interest of pluripotent cells and ethical issues related to the establishment of human embryonic stem cell (ESC) or embryonic germ cell (EGC) lines raise the understanding of the mechanism underlying pluripotency to a fundamental issue. Establishing a protein pluripotency signature for these cells can be complicated by the presence of unrelated proteins produced by the culture environment. Here, we have analyzed the environment supporting ESC and EGC growth, and established 2-D reference maps for each constituent present in this culture environment: mouse embryonic fibroblast feeder cells, culture medium (CM) and gelatin. The establishment of these reference maps is essential prior to the study of ESC and EGC specific proteomes. Indeed, these maps can be subtracted from ESC or EGC maps to allow focusing on spots specific for ESCs or EGCs. Our study led to the identification of 110 unique proteins from fibroblast feeder cells and 23 unique proteins from the CM, which represent major contaminants of ESC and EGC proteomes. For gelatin, no collagen-specific proteins were identified, most likely due to difficulties in resolution and low quantities. Furthermore, no differences were observed between naive and conditioned CM. Finally, we compared these reference maps to ESC 2-D gels and isolated 17 ESC specific spots. Among these spots, proteins that had already been identified in previous human and mouse ESC proteomes were identified but no apparent ESC-specific pluripotency marker could be identified. This work represents an essential step in furthering the knowledge of environmental factors supporting ESC and EGC growth. [source] Paralog of the formylglycine-generating enzyme , retention in the endoplasmic reticulum by canonical and noncanonical signalsFEBS JOURNAL, Issue 6 2008Santosh Lakshmi Gande Formylglycine-generating enzyme (FGE) catalyzes in newly synthesized sulfatases the oxidation of a specific cysteine residue to formylglycine, which is the catalytic residue required for sulfate ester hydrolysis. This post-translational modification occurs in the endoplasmic reticulum (ER), and is an essential step in the biogenesis of this enzyme family. A paralog of FGE (pFGE) also localizes to the ER. It shares many properties with FGE, but lacks formylglycine-generating activity. There is evidence that FGE and pFGE act in concert, possibly by forming complexes with sulfatases and one another. Here we show that human pFGE, but not FGE, is retained in the ER through its C - terminal tetrapeptide PGEL, a noncanonical variant of the classic KDEL ER-retention signal. Surprisingly, PGEL, although having two nonconsensus residues (PG), confers efficient ER retention when fused to a secretory protein. Inducible coexpression of pFGE at different levels in FGE-expressing cells did not significantly influence the kinetics of FGE secretion, suggesting that pFGE is not a retention factor for FGE in vivo. PGEL is accessible at the surface of the pFGE structure. It is found in 21 mammalian species with available pFGE sequences. Other species carry either canonical signals (eight mammals and 26 nonmammals) or different noncanonical variants (six mammals and six nonmammals). Among the latter, SGEL was tested and found to also confer ER retention. Although evolutionarily conserved for mammalian pFGE, the PGEL signal is found only in one further human protein entering the ER. Its consequences for KDEL receptor-mediated ER retrieval and benefit for pFGE functionality remain to be fully resolved. [source] The metabolic role and evolution of l -arabinitol 4-dehydrogenase of Hypocrea jecorinaFEBS JOURNAL, Issue 10 2004Manuela Pail l -Arabinitol 4-dehydrogenase (Lad1) of the cellulolytic and hemicellulolytic fungus Hypocrea jecorina (anamorph: Trichoderma reesei) has been implicated in the catabolism of l -arabinose, and genetic evidence also shows that it is involved in the catabolism of d -xylose in xylitol dehydrogenase (xdh1) mutants and of d -galactose in galactokinase (gal1) mutants of H. jecorina. In order to identify the substrate specificity of Lad1, we have recombinantly produced the enzyme in Escherichia coli and purified it to physical homogeneity. The resulting enzyme preparation catalyzed the oxidation of pentitols (l -arabinitol) and hexitols (d -allitol, d -sorbitol, l -iditol, l -mannitol) to the same corresponding ketoses as mammalian sorbitol dehydrogenase (SDH), albeit with different catalytic efficacies, showing highest kcat/Km for l -arabinitol. However, it oxidized galactitol and d -talitol at C4 exclusively, yielding l -xylo-3-hexulose and d -arabino-3-hexulose, respectively. Phylogenetic analysis of Lad1 showed that it is a member of a terminal clade of putative fungal arabinitol dehydrogenase orthologues which separated during evolution of SDHs. Juxtapositioning of the Lad1 3D structure over that of SDH revealed major amino acid exchanges at topologies flanking the binding pocket for d -sorbitol. A lad1 gene disruptant was almost unable to grow on l -arabinose, grew extremely weakly on l -arabinitol, d -talitol and galactitol, showed reduced growth on d -sorbitol and d -galactose and a slightly reduced growth on d -glucose. The weak growth on l -arabinitol was completely eliminated in a mutant in which the xdh1 gene had also been disrupted. These data show not only that Lad1 is indeed essential for the catabolism of l -arabinose, but also that it constitutes an essential step in the catabolism of several hexoses; this emphasizes the importance of such reductive pathways of catabolism in fungi. [source] Why does Candida albicans switch?FEMS YEAST RESEARCH, Issue 7 2009David R. Soll Abstract White,opaque switching in Candida albicans was first discovered in 1987. Fifteen years later, and three years after the discovery of the mating system, it was demonstrated that the switch from white to opaque was an essential step in the mating process. But this latter discovery did not reveal why C. albicans had this requirement, when Saccharomyces cerevisiae and other hemiascomycetes did not. The discovery that mating-competent opaque cells signaled mating-incompetent white cells, through the release of pheromones, to become adhesive and form biofilms provided a clue to this fundamental question. Opaque cells appeared to signal white cells to form biofilms that facilitated mating by protecting the fragile gradients of the pheromone that directed chemotropism, a process necessary for fusion. Here, we explore the discoveries and observations that have led to this hypothesis, and the ancillary questions that have risen that are related to the regulation of the unique pheromone response, the evolution of this response and the relationship between pheromone-enhanced white cell biofilms and ,asexual' biofilms formed by a/, cells. This discussion, therefore, focuses on a unique and complex component of the basic biology of C. albicans that relates switching, mating and pathogenesis. [source] Blockage of voltage-gated calcium signaling impairs migration of glial cells in vivoGLIA, Issue 3 2005Christian Lohr Abstract Migration of glial cells is an essential step in the development of the antennal lobe, the primary olfactory center of insects, to establish well-defined borders between olfactory glomeruli required for odor discrimination. In the present study, we used two-photon microscopy to visualize calcium signaling in developing antennal lobe glial cells of the sphinx moth Manduca sexta. We found a correlation between the upregulation of functional voltage-gated calcium channels and the onset of glial cell migration. In addition, glial cells migrating into the center of the antennal lobe express larger voltage-gated calcium transients than glial cells that remain at the periphery. Migration behavior and calcium signaling of glial cells in vivo were manipulated either by deafferentation, by injection of the calcium channel blockers diltiazem, verapamil, and flunarizine, or by injection of the calcium chelators BAPTA-AM and Fluo-4-AM. In deafferented antennal lobes, glial cells failed to express functional voltage-gated calcium channels and did not migrate. Calcium channel blockage or reducing glial calcium signals by calcium chelators prevented glial cell migration and resulted in antennal lobes lacking glial borders around glomeruli, indicating that voltage-gated calcium signaling is required for the migration of antennal lobe glial cells and the development of mature olfactory glomeruli. © 2005 Wiley-Liss, Inc. [source] Role of the Charge Transfer State in Organic Donor,Acceptor Solar CellsADVANCED MATERIALS, Issue 37 2010Carsten Deibel Charge transfer complexes are interfacial charge pairs residing at the donor,acceptor heterointerface in organic solar cell. Experimental evidence shows that it is crucial for the photovoltaic performance, as both photocurrent and open circuit voltage directly depend on it. For charge photogeneration, charge transfer complexes represent the intermediate but essential step between exciton dissotiation and charge extraction. Recombination of free charges to the ground state is via the bound charge transfer state before being lost to the ground state. In terms of the open circuit voltage, its maximum achievable value is determined by the energy of the charge transfer state. An important question is whether or not maximum photocurrent and maximum open circuit voltage can be achieved simultaneously. The impact of increasing the CT energy,in order to raise the open circuit voltage, but lowering the kinetic excess energy of the CT complexes at the same time,on the charge photogeneration will accordingly be discussed. Clearly, the fundamental understanding of the processes involving the charge transfer state is essential for an optimisation of the performance of organic solar cells. [source] Step-by-Step Build-Up of Biologically Active Cell-Containing Stratified Films Aimed at Tissue EngineeringADVANCED MATERIALS, Issue 6 2009Laurent Grossin Alginate gel layers containing viable cells with adjacent bioactive polyelectrolyte multilayers are fabricated, and their bioactivity is shown to originate mainly from the degradation of the cells. Alternate biofunctionalized multilayers and cell-containing layers are shown to be an essential step toward fabrication of stratified architectures, and tuning the cellular activity is possible by controlling the position of active molecules. [source] Infiltration and Inversion of Holographically Defined Polymer Photonic Crystal Templates by Atomic Layer Deposition,ADVANCED MATERIALS, Issue 12 2006S. King Practical methods of microfabrication are vital for the development of photonic-crystal-based signal processing. However, extension of the optical methods that dominate integrated circuit fabrication to three dimensions is challenging. This communication reports an essential step for creation of devices operating within a full photonic band gap: atomic layer deposition is used to create the high-index TiO2 replicas of holographically defined photonic crystals shown in the figure. [source] An approach for the calculation of magnetic field within square spiral inductors at low frequencyINTERNATIONAL JOURNAL OF NUMERICAL MODELLING: ELECTRONIC NETWORKS, DEVICES AND FIELDS, Issue 4 2002Noureddin M. Ibrahim Abstract The magnetic field distribution within a square spiral inductor is investigated in this paper by summing closed-form expressions for the fields from each segment. Plots illustrating the variation of the normally directed B -field penetrating the surface of the spiral traces are then developed for a variety of perspectives. The expressions and insight gained represent an essential step in developing a detailed model of effects such as current crowding, which significantly limit the spiral's performance in practical circuits. Copyright © 2002 John Wiley & Sons, Ltd. [source] Strategies for identifying genes that play a role in spinal cord regenerationJOURNAL OF ANATOMY, Issue 1 2004M. Wintzer Abstract A search for genes that promote or block CNS regeneration requires numerous approaches; for example, tests can be made on individual candidate molecules. Here, however, we describe methods for comprehensive identification of genes up- and down-regulated in neurons that can and cannot regenerate after injury. One problem concerns identification of low-abundance genes out of the 30 000 or so genes expressed by neurons. Another difficulty is knowing whether a single gene or multiple genes are necessary. When microchips and subtractive differential display are used to identify genes turned on or off, the numbers are still too great to test which molecules are actually important for regeneration. Candidates are genes coding for trophic, inhibitory, receptor and extracellular matrix molecules, as well as unknown genes. A preparation useful for narrowing the search is the neonatal opossum. The spinal cord and optic nerve can regenerate after injury at 9 days but cannot at 12 days after birth. This narrow window allows genes responsible for the turning off of regeneration to be identified. As a next step, sites at which they are expressed (forebrain, midbrain, spinal cord, neurons or glia, intracellular or extracellular) must be determined. An essential step is to characterize proteins, their levels of expression, and their importance for regeneration. Comprehensive searches for molecular mechanisms represent a lengthy series of experiments that could help in devising strategies for repairing injured spinal cord. [source] A model of bovine tuberculosis in the badger Melesmeles: an evaluation of control strategiesJOURNAL OF APPLIED ECOLOGY, Issue 3 2001G.C. Smith Summary 1,An individual-based stochastic simulation model was used to investigate the control of bovine tuberculosis (TB) in the European badger Meles meles. Nearly all population and epidemiological parameters were derived from one study site, and the transmission of TB from badgers to cattle was included. The latter is an essential step if reactive badger control strategies are to be modelled. 2,The model appeared to underestimate slightly the rate of population recovery following widespread culling. This may have been due to simulating an isolated population with no immigration and no compensatory increase in fecundity. This should not affect the relative efficacy of each control strategy, but does require further investigation. 3,Of the historical methods of badger control, gassing and the ,clean ring' strategies were the most effective at reducing disease prevalence in the badger and cattle herd breakdown rates. These results agree with those of earlier models. 4,The proactive badger removal operation as part of the current field trial should cause a dramatic decrease in the number of cattle herd breakdowns, but also has the greatest effect on the badger population size. 5,The proactive use of a live test to detect TB, followed by vaccination, appears to reduce substantially cattle herd breakdowns and disease prevalence in the badger. 6,Three combined control strategies gave the best initial reduction in cattle herd breakdown rate and disease prevalence in the badger: (i) a proactive cull followed by reactive test and cull; (ii) a continued vaccination and proactive test and cull; and (iii) a continuous proactive test and cull. 7,The results of simulation models suggest that badger vaccination is a very good method of TB control. This is at odds with simple models and requires further investigation. [source] Microscopic observation of aerobic granulation in sequential aerobic sludge blanket reactorJOURNAL OF APPLIED MICROBIOLOGY, Issue 1 2001J.-H. Tay Aims: This paper attempts to provide visual evidence of how aerobic granulation evolves in sequential aerobic sludge blanket reactors. Methods and Results: A series of experiments were conducted in two column-type sequential aerobic sludge reactors fed with glucose and acetate as sole carbon source, respectively. The evolution of aerobic granulation was monitored using image analysis and optical and scanning electron microscopy. The results indicated that the formation of aerobic granules was a gradual process from seed sludge to compact aggregates, further to granular sludge and finally to mature granules with the sequential operation proceeding. Glucose- and acetate-fed granules have comparable characteristics in terms of settling velocity, size, shape, biomass density and microbial activity. However, the microbial diversity of the granules was associated with the carbon source supplied. In this work, an important aerobic starvation phase was identified during sequential operation cycles. It was found that periodical aerobic starvation was an effective trigger for microbial aggregation in the reactor and further strengthened cell,cell interaction to form dense aggregates, which was an essential step of granulation. The periodical starvation-induced aggregates would finally be shaped to granules by hydrodynamic shear and flow. Conclusions: Aerobic granules can be formed within 3 weeks in the systems. The periodical starvation and hydrodynamic conditions would play a crucial role in the granulation process. Significance and Impact of the Study: Aerobic granules have excellent physical characteristics as compared with conventional activated sludge flocs. This research could be helpful for the development of an aerobic granule-based novel type of reactor for handling high strength organic wastewater. [source] Pollen,plant,climate relationships in sub-Saharan AfricaJOURNAL OF BIOGEOGRAPHY, Issue 3 2007Julie Watrin Abstract Aim, To demonstrate that incorporating the bioclimatic range of possible contributor plants leads to improved accuracy in interpreting the palaeoclimatic record of taxonomically complex pollen types. Location, North Tropical Africa. Methods, The geographical ranges of selected African plants were extracted from the literature and geo-referenced. These plant ranges were compared with the pollen percentages obtained from a network of surface sediments. Climate-response surfaces were graphed for each pollen taxon and each corresponding plant species. Results, Several patterns can be identified, including taxa for which the pollen and plant distributions coincide, and others where the range limits diverge. Some pollen types display a reduced climate range compared with that of the corresponding plant species, due to low pollen production and/or dispersal. For other taxa, corresponding to high pollen producers such as pioneer taxa, pollen types display a larger climatic envelope than that of the corresponding plants. The number of species contained in a pollen taxon is an important factor, as the botanical species included in a taxon may have different geographical and climate distributions. Main conclusions, The comparison between pollen and plant distributions is an essential step towards more precise vegetation and climate reconstructions in Africa, as it identifies taxa that have a high correspondence between pollen and plant distribution patterns. Our method is a useful tool to reassess biome reconstructions in Africa and to characterize accurately the vegetation and climate conditions at a regional scale, from pollen data. [source] Alterations in the temporal expression and function of cadherin-7 inhibit cell migration and condensation during chondrogenesis of chick limb mesenchymal cells in vitroJOURNAL OF CELLULAR PHYSIOLOGY, Issue 1 2009Dongkyun Kim Endochondral bone formation requires a complex interplay among immature mesenchymal progenitor cells to form the cartilaginous anlagen, which involves migration, aggregation and condensation. Even though condensation of chondrogenic progenitors is an essential step in this process, its mechanism(s) has not been well studied. Here, we show that cadherin-7 plays a central role in cellular condensation by modulating cell motility and migration. In this study, many mesenchymal cells failed to migrate, and precartilage condensation was inhibited, after knockdown of endogenous cadherin-7 levels. Exposure of mesenchymal cells to SB203580 (a specific inhibitor of p38MAPK), LiCl (an inhibitor of GSK-3,) or overexpression of ,-catenin resulted in inhibition of cadherin-7 levels and, subsequently, suppression of cell migration. Collectively, our results suggest that cadherin-7 controls cell migration in chick limb bud mesenchymal cells, and that p38MAPK and GSK signals are responsible for regulating cadherin-7-mediated cell migration. J. Cell. Physiol. 221: 161,170, 2009. © 2009 Wiley-Liss, Inc [source] Production of polyhydroxyalkanoates: the future green materials of choiceJOURNAL OF CHEMICAL TECHNOLOGY & BIOTECHNOLOGY, Issue 6 2010Everest Akaraonye Abstract Polyhydroxyalkanoates (PHAs) have recently been the focus of attention as a biodegradable and biocompatible substitute for conventional non degradable plastics. The cost of large-scale production of these polymers has inhibited its widespread use. Thus, economical, large-scale production of PHAs is currently being studied intensively. Various bacterial strains, either wild-type or recombinant have been utilized with a wide spectrum of utilizable carbon sources. New fermentation strategies have been developed for the efficient production of PHAs at high concentration and productivity. With the current advances, PHAs can now be produced to a concentration of 80 g L,1 with productivities greater than 4 g PHA L,1 h,1. These advances will further lower the production cost of PHAs and allow this family of polymers to become a leading biodegradable polymer in the near future. This review describes the properties of PHAs, their uses, the various attempts towards the production of PHAs, focusing on the utilization of cheap substrates and the development of different fermentation strategies for the production of these polymers, an essential step forward towards their widespread use. Copyright © 2010 Society of Chemical Industry [source] Discrimination of dynamical system models for biological and chemical processesJOURNAL OF COMPUTATIONAL CHEMISTRY, Issue 8 2007Sönke Lorenz Abstract In technical chemistry, systems biology and biotechnology, the construction of predictive models has become an essential step in process design and product optimization. Accurate modelling of the reactions requires detailed knowledge about the processes involved. However, when concerned with the development of new products and production techniques for example, this knowledge often is not available due to the lack of experimental data. Thus, when one has to work with a selection of proposed models, the main tasks of early development is to discriminate these models. In this article, a new statistical approach to model discrimination is described that ranks models wrt. the probability with which they reproduce the given data. The article introduces the new approach, discusses its statistical background, presents numerical techniques for its implementation and illustrates the application to examples from biokinetics. © 2007 Wiley Periodicals, Inc. J Comput Chem, 2007 [source] The influence of temporal cake moisture content on a discontinuous washing process in the centrifugal fieldAICHE JOURNAL, Issue 3 2009Franky Ruslim Abstract In solid/liquid separation processes, filter cake washing is an essential step in improving the quality of particulate products by elimination of impurities. During cake washing and dewatering, the cake saturation changes depending on the flow conditions and it cannot always be measured and controlled accurately. This article deals with investigations on the influence of the initial and temporal cake saturation on washing PVC and silica sand particles in the centrifugal field. It was found, that high initial saturation levels and high maximum saturations during the washing process had a positive impact in inducing a high hydrostatic pressure for advective flow and enabling a homogeneous distribution of the wash water inside the cake. This was achieved by increasing the wash water flux and/or decreasing the g-factor. A good method to obtain low final impurity quantity is the combination of washing at a low g-factor and dewatering at a high one. © 2009 American Institute of Chemical Engineers AIChE J, 2009 [source] Clonal nature of odontogenic tumoursJOURNAL OF ORAL PATHOLOGY & MEDICINE, Issue 4 2009Carolina Cavaliéri Gomes Background:, Although clonal origin is an essential step in the comprehension of neoplasias, there have been no studies to examine whether odontogenic tumours are derived from a single somatic progenitor cell. The purpose of this study was to investigate the clonal origin of odontogenic tumours. Methods:, Fresh samples of seven ameloblastomas, two odontogenic mixomas, two adenomatoid odontogenic tumour, one calcifying odontogenic cyst, one calcifying epithelial odontogenic tumour (CEOT) and six odontogenic keratocyst (OKC) of female patients were included in this study. After DNA extraction, the HUMARA gene polymorphism assay was performed. Results:, Most of the informative odontogenic lesions studied (12 out of 16) showed a monoclonal pattern. Among the polyclonal cases, two were OKC, one CEOT and one odontogenic mixoma. Conclusions:, Our results suggest that most odontogenic tumours are monoclonal. [source] IMPACT OF MAGMATISM ON PETROLEUM SYSTEMS IN THE SVERDRUP BASIN, CANADIAN ARCTIC ISLANDS, NUNAVUT: A NUMERICAL MODELLING STUDYJOURNAL OF PETROLEUM GEOLOGY, Issue 3 2007S.F. Jones Numerical modelling is used to investigate for the first time the interactions between a petroleum system and sill intrusion in the NE Sverdrup Basin, Canadian Arctic Archipelago. Although hydrocarbonexploration has been successful in the western Sverdrup Basin, the results in the NE part of thebasin have been disappointing, despite the presence of suitable Mesozoic source rocks, migrationpaths and structural/stratigraphic traps, many involving evaporites. This was explained by (i) theformation of structural traps during basin inversion in the Eocene, after the main phase ofhydrocarbon generation, and/or (ii) the presence of evaporite diapirs locally modifying the geothermalgradient, leading to thermal overmaturity of hydrocarbons. This study is the first attempt at modellingthe intrusion of Cretaceous sills in the east-central Sverdrup Basin, and to investigate how theymay have affected the petroleum system. A one-dimensional numerical model, constructed using PetroMod9.0®, investigates the effectsof rifting and magmatic events on the thermal history and on petroleum generation at the DepotPoint L-24 well, eastern Axel Heiberg Island (79°23,40,N, 85°44,22,W). The thermal history isconstrained by vitrinite reflectance and fission-track data, and by the tectonic history. The simulationidentifies the time intervals during which hydrocarbons were generated, and illustrates the interplaybetween hydrocarbon production and igneous activity at the time of sill intrusion during the EarlyCretaceous. The comparison of the petroleum and magmatic systems in the context of previouslyproposed models of basin evolution and renewed tectonism was an essential step in the interpretationof the results from the Depot Point L-24 well. The model results show that an episode of minor renewed rifting and widespread sill intrusionin the Early Cretaceous occurred after hydrocarbon generation ceased at about 220 Ma in theHare Fiord and Van Hauen Formations. We conclude that the generation potential of these deeperformations in the eastern Sverdrup Basin was not likely to have been affected by the intrusion ofmafic sills during the Early Cretaceous. However, the model suggests that in shallower sourcerocks such as the Blaa Mountain Formation, rapid generation of natural gas occurred at 125 Ma, contemporaneous with tectonic rejuvenation and sill intrusion in the east-central Sverdrup Basin. A sensitivity study shows that the emplacement of sills increased the hydrocarbon generation ratesin the Blaa Mountain Formation, and facilitated the production of gas rather than oil. [source] Rarity and decline in palaeoendemic Martino's vole Dinaromys bogdanoviMAMMAL REVIEW, Issue 4 2008BORIS KRY, TUFEK ABSTRACT 1Martino's vole Dinaromys bogdanovi is the only living member of the Tertiary genus Dinaromys, and probably also the only surviving member of the Pliomys lineage. The range of the genus Dinaromys has historically been small and its rate of evolution has been low. 2Martino's vole shows all three attributes of rarity in accordance with Rabinowitz's ,seven forms of rarity' model: (i) its range is estimated at 43 545 km2 but the area of occupancy is <5200 km2; (ii) its habitat requirements are narrow and the species is strictly tied to exposed, karstified bedrock; and (iii) current populations are invariably small and frequently isolated. 3The Pleistocene range of Martino's vole exceeded the recent one, at least in the north-western part of the Balkans, and its shrinkage continued into the Holocene. 4Martino's vole may be in competition with the European snow vole Chionomys nivalis, which has a very similar morphology and presumably identical habitat requirements, but is shifted towards an r-selected life-history strategy. Long-term sympatry of these voles has probably resulted in competitive exclusion of the relatively K-selected Martino's vole by the relatively r-selected European snow vole. 5Martino's vole consists of two deeply divergent (about one million years ago) phylogeographical lineages, which may represent distinct cryptic species. Rarity is particularly pronounced in the north-western lineage to the west of the Neretva River, where rocky habitats are largely occupied by the European snow vole. 6In the IUCN Red List of Threatened Animals, Martino's vole is classified as ,near threatened'. However, the north-western lineage, which is phylogeographically most divergent and has the greatest genetic diversity, is classed as a ,vulnerable' evolutionary significant unit on the basis of its small area of occupancy (<2000 km2). Long-term population monitoring is an essential step in evaluating the conservation needs of Martino's vole. [source] Defining characteristics of educational competenciesMEDICAL EDUCATION, Issue 3 2008Mark A Albanese Context, Doctor competencies have become an increasing focus of medical education at all levels. However, confusion exists regarding what constitutes a competency versus a goal, objective or outcome. Objectives, This article attempts to identify the characteristics that define a competency and proposes criteria that can be applied to distinguish between competencies, goals, objectives and outcomes. Methods, We provide a brief overview of the history of competencies and compare competencies identified by international medical education organisations (CanMEDS 2005, Institute for International Medical Education, Dundee Outcome Model, Accreditation Council for Graduate Medical Education/American Board of Medical Specialties). Based upon this review and comparisons, as well as on definitions of competencies from the literature and theoretical and conceptual analyses of the underpinnings of competencies, the authors develop criteria that can serve to distinguish competencies from goals, objectives and outcomes. Results, We propose 5 criteria which can be used to define a competency: it focuses on the performance of the end-product or goal-state of instruction; it reflects expectations that are external to the immediate instructional programme; it is expressible in terms of measurable behaviour; it uses a standard for judging competence that is not dependent upon the performance of other learners, and it informs learners, as well as other stakeholders, about what is expected of them. Conclusions, Competency-based medical education is likely to be here for the foreseeable future. Whether or not these 5 criteria, or some variation of them, become the ultimate defining criteria for what constitutes a competency, they represent an essential step towards clearing the confusion that reigns. [source] HIV-1 integrase inhibitors: 2005,2006 updateMEDICINAL RESEARCH REVIEWS, Issue 1 2008Raveendra Dayam Abstract HIV-1 integrase (IN) catalyzes the integration of proviral DNA into the host genome, an essential step for viral replication. Inhibition of IN catalytic activity provides an attractive strategy for antiretroviral drug design. Currently two IN inhibitors, MK-0518 and GS-9137, are in advanced stages of human clinical trials. The IN inhibitors in clinical evaluation demonstrate excellent antiretroviral efficacy alone or in combination regimens as compared to previously used clinical antiretroviral agents in naive and treatment-experienced HIV-1 infected patients. However, the emergence of viral strains resistant to clinically studied IN inhibitors and the dynamic nature of the HIV-1 genome demand a continued effort toward the discovery of novel inhibitors to keep a therapeutic advantage over the virus. Continued efforts in the field have resulted in the discovery of compounds from diverse chemical classes. In this review, we provide a comprehensive report of all IN inhibitors discovered in the years 2005 and 2006. © 2007 Wiley Periodicals, Inc. Med Res Rev, 28, No. 1, 118,154, 2008 [source] Standardized Stimulation Protocol to Predict the Long-Term Success of Radiofrequency Ablation of Postinfarction Ventricular TachycardiaPACING AND CLINICAL ELECTROPHYSIOLOGY, Issue 1p2 2003DAVID O'DONNELL O'DONNELL, D., et al.: Standardized Stimulation Protocol to Predict the Long-Term Success of Radiofrequency Ablation of Postinfarction Ventricular Tachycardia.Background: The ability to predict the success of radiofrequency ablation (RFA) is an essential step in the management of ventricular tachycardia (VT) in patients with ischemic heart disease. Methods: This study tested a standardized programmed stimulation protocol and pre-specified definitions of procedural outcome. Consecutive patients referred for RFA of delayed post infarction VT were enrolled. Programmed stimulation was performed at the beginning and the end of an RFA procedure, and consisted of an 8 beat drive followed by up to 5 extrastimuli. Immediate success was defined as no inducible monomorphic VT, and a modified result was defined as the inducibility of VT with >2 extrastimuli beyond those required at baseline. Procedural failure was defined when these criteria were not met. Recurrences of sustained VT and arrhythmic deaths were monitored during long-term follow-up. Results: The study enrolled 112 patients. Immediate procedural success was achieved in 38%, a modified result in 34%, and procedural failure in 28% of patients. During a mean follow-up of 78 ± 16 months, recurrent sustained VT was observed in 25 patients. VT recurrence was 3% (3/79) in patients with a successful or modified result, compared with 67% (22/33) in those who had undergone unsuccessful procedures (P < 0.001). Conclusions: This standardized stimulation protocol and definitions of procedural success, enabled us to predict with high accuracy a VT recurrence-free long-term follow-up. This may have implications in recommending devices or other treatments after RFA for postinfarction VT. (PACE 2003; 26[Pt. II]:348,351) [source] Structural Effects on the Electronic Absorption Properties of 5,6-Dihydroxyindole Oligomers: The Potential of an Integrated Experimental and DFT Approach to Model Eumelanin Optical Properties,PHOTOCHEMISTRY & PHOTOBIOLOGY, Issue 3 2008Marco D'Ischia Elucidation of the relationships between structural features and UV,visible absorption properties of 5,6-dihydroxyindole oligomers is an essential step towards an understanding of the unique optical properties of eumelanins. Herein, we report the first combined experimental and density functional theory (DFT) investigation of the 5,6-dihydroxyindole oligomers so far isolated. 2,2,-Biindolyl 2 and the 2,4,-biindolyl 3 absorb at longer wavelengths relative to 2,7,-biindolyl 4 and their spectra were well predicted by DFT analysis. The absorption bands of 2,4,:2,,4,,- and 2,4,:2,,7,,-triindolyls 5 and 6 also fall at different wavelengths and can be interpreted by DFT simulations as being due to a combination of two main separate transitions. Tetramer 7, in which two 2,4,-biindolyl units are linked through a 2,3,-connection, exhibits a broad chromophore extending over the entire UV range without well defined absorption maxima. Within the dimer,tetramer range examined, three key points emerge: (1) an increase in oligomer chain length does not result in any regular and predictable bathochromic shift; (2) a marked broadening of the absorption bands occurs when going from the monomer to the tetramer structure; and (3) the mode of coupling of the indole units is a crucial, hitherto unrecognized, structural parameter affecting the electronic absorption properties of 5,6-dihydroxyindole oligomers. It is concluded that use of experimentally characterized oligomeric scaffolds as a basis for DFT calculations is a most promising approach to building reliable structural models for studies of eumelanins optical properties. [source] Side chain substitution benchmark for peptide/MHC interactionPROTEIN SCIENCE, Issue 6 2008Bernhard Knapp Abstract The prediction of T-cell epitopes is an essential part in virtual immunology. Apart from sequence-based techniques, which achieve good results but fail to give insight into the binding behavior of a certain peptide binding to a major histocompatibility complex, structure-based approaches are another important technique. An essential step is the correct placement of the side chains for a given peptide in cases where no experimental data for the structure are available. To our knowledge, no benchmark for side chain substitution in the area of HLA has been reported in the literature. Here, we present a comparison of five different tools (SCWRL, SCATD, SPDBV, SCit, IRECS) applicable for side chain substitution. Each tool is tested on 29 different HLA-A2 structures with experimentally known side chain positions. Parts of the benchmark are correctness, reliability, runtime, and usability. For validation, the root mean square deviations between X-ray structures and predicted structures are used. All tools show different strengths and weaknesses. [source] The role of inflammatory and parenchymal cells in acute pancreatitis,THE JOURNAL OF PATHOLOGY, Issue 3 2007A Vonlaufen Abstract The infiltration of inflammatory cells into the pancreas is an early and central event in acute pancreatitis that promotes local injury and systemic complications of the disease. Recent research has yielded the important finding that resident cells of the pancreas (particularly acinar and pancreatic stellate cells) play a dynamic role in leukocyte attraction via secretion of chemokines and cytokines and expression of adhesion molecules. Significant progress has been made in recent years in our understanding of the role of leukocyte movement (adhesion to the blood vessel wall, transmigration through the blood vessel wall and infiltration into the parenchyma) in the pathophysiology of acute pancreatitis. This review discusses recent studies and describes the current state of knowledge in the field. It is clear that detailed elucidation of the numerous processes in the inflammatory cascade is an essential step towards the development of improved therapeutic strategies in acute pancreatitis. Studies to date suggest that combination therapy targeting different steps of the inflammatory cascade may be the treatment of choice for this disease. Copyright © 2007 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [source] Plant-insect interactions: what can we learn from plant lectins?ARCHIVES OF INSECT BIOCHEMISTRY AND PHYSIOLOGY (ELECTRONIC), Issue 4 2010Katrien Michiels Abstract Many plant lectins have high anti-insect potential. Although the effects of most lectins are only moderately influencing development or population growth of the insect, some lectins have strong insecticidal properties. In addition, some studies report a deterrent activity towards feeding and oviposition behavior. Transmission of plant lectins to the next trophic level has been investigated for several tritrophic interactions. Effects of lectins with different sugar specificities can vary substantially with the insect species under investigation and with the experimental setup. Lectin binding in the insect is an essential step in exerting a toxic effect. Attempts have been made to study the interactions of lectins in several insect tissues and to identify lectin-binding receptors. Ingested lectins generally bind to parts of the insect gut. Furthermore, some lectins such as the Galanthus nivalus agglutinin (GNA) cross the gut epithelium into the hemolymph and other tissues. Recently, several candidate lectin-binding receptors have been isolated from midgut extracts. To date little is known about the exact mechanism for insecticidal activity of plant lectins. However, insect glycobiology is an emerging research field and the recent technological advances in the analysis of lectin carbohydrate specificities and insect glycobiology will certainly lead to new insights in the interactions between plant lectins and insects, and to a better understanding of the molecular mechanisms involved. © 2010 Wiley Periodicals, Inc. [source] Structure-assisted discovery of an aminothiazole derivative as a lead molecule for inhibition of bacterial fatty-acid synthesisACTA CRYSTALLOGRAPHICA SECTION D, Issue 12 2007Günter Pappenberger Fatty-acid synthesis in bacteria is of great interest as a target for the discovery of antibacterial compounds. The addition of a new acetyl moiety to the growing fatty-acid chain, an essential step in this process, is catalyzed by ,-ketoacyl-ACP synthase (KAS). It is inhibited by natural antibiotics such as cerulenin and thiolactomycin; however, these lack the requirements for optimal drug development. Structure-based biophysical screening revealed a novel synthetic small molecule, 2-phenylamino-4-methyl-5-acetylthiazole, that binds to Escherichia coli KAS I with a binding constant of 25,µM as determined by fluorescence titration. A 1.35,Å crystal structure of its complex with its target reveals noncovalent interactions with the active-site Cys163 and hydrophobic residues of the fatty-acid binding pocket. The active site is accessible through an open conformation of the Phe392 side chain and no conformational changes are induced at the active site upon ligand binding. This represents a novel binding mode that differs from thiolactomycin or cerulenin interaction. The structural information on the protein,ligand interaction offers strategies for further optimization of this low-molecular-weight compound. [source] | |||||||||||||||||||||||||||||||