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Systematic Analysis (systematic + analysis)
Selected AbstractsThe significance of a small, level-3 ,semi evacuation' hospital in a terrorist attack in a nearby townDISASTERS, Issue 3 2007Moshe Pinkert Terrorist attacks can occur in remote areas causing mass-casualty incidents MCIs far away from level-1 trauma centres. This study draws lessons from an MCI pertaining to the management of primary and secondary evacuation and the operational mode practiced. Data was collected from formal debriefings during and after the event, and the medical response, interactions and main outcomes analysed using Disastrous Incidents Systematic Analysis through Components, Interactions and Results (DISAST-CIR) methodology. A total of 112 people were evacuated from the scene,66 to the nearby level 3 Laniado hospital, including the eight critically and severely injured patients. Laniado hospital was instructed to act as an evacuation hospital but the flow of patients ended rapidly and it was decided to admit moderately injured victims. We introduce a novel concept of a ,semi-evacuation hospital'. This mode of operation should be selected for small-scale events in which the evacuation hospital has hospitalization capacity and is not geographically isolated. We suggest that level-3 hospitals in remote areas should be prepared and drilled to work in semi-evacuation mode during MCIs. [source] Academic Writing and Genre: A Systematic Analysis,by BRUCE, IANMODERN LANGUAGE JOURNAL, Issue 3 2009HOSSEIN NASSAJI No abstract is available for this article. [source] A Systematic Analysis of Coal Accumulation ProcessACTA GEOLOGICA SINICA (ENGLISH EDITION), Issue 3 2008CHENG Aiguo Abstract: Formation of coal seam and coal-rich zone is an integrated result of a series of factors in coal accumulation process. The coal accumulation system is an architectural aggregation of coal accumulation factors. It can be classified into 4 levels: the global coal accumulation super-system, the coal accumulation domain mega-system, the coal accumulation basin system, and the coal seam or coal seam set sub-system. The coal accumulation process is an open, dynamic, and grey system, and is meanwhile a system with such natures as aggregation, relevance, entirety, purpose-orientated, hierarchy, and environment adaptability. In this paper, we take coal accumulation process as a system to study origin of coal seam and coal-rich zone; and we will discuss a methodology of the systematic analysis of coal accumulation process. As an example, the Ordos coal basin was investigated to elucidate the application of the method of the coal accumulation system analysis. [source] Management Behaviour as Social Capital: A Systematic Analysis of Organizational EthnographiesBRITISH JOURNAL OF INDUSTRIAL RELATIONS, Issue 1 2005Randy Hodson This article explores managerial behaviour as a potential source of social capital in the workplace. Using content-coded data from the full population of organizational ethnographies (N = 204), we explore facets of workplace behaviours and relations that have been difficult to evaluate using survey-based techniques. Analysing ethnographic-based data with multivariate techniques, we find that competent management leadership, in particular, has widespread and significant effects on important workplace outcomes such as job satisfaction, organizational citizenship behaviour, and co-worker infighting. The findings highlight the value of cross-methods techniques for evaluating and extending existing workplace theories. [source] Transcriptional activities of mutant p53: When mutations are more than a lossJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 5 2004Ella Kim Abstract The dominant oncogenic properties of mutant p53 have been recognized as a phenomenon associated with tumor progression a long time ago, even before it was realized that the major function of wild type p53 is that of a tumor suppressor. Recent advances in this fascinating area in tumor cell biology reveal that the community of mutant p53 proteins is comprised of proteins that are extremely diverse both structurally and functionally, and elicit a multitude of cellular responses that not only are entirely distinct from those mediated by wild type p53, but also vary among different mutant p53 proteins. Aberrant regulation of transcription is one of the mechanisms underlying the ability of some mutant p53 proteins to act as oncogenic factors. Systematic analyses of the transcriptional activities of mutant p53 suggest that not the loss of transcriptional activity as such, but alterations of target DNA selectivity may be the driving force of mutant p53 specific transcription underlying the growth-promoting effects of mutant p53. This article focuses on mechanistic aspects of mutp53 "gain-of-function" with the emphasis on possible mechanisms underlying transcriptional activation by mutp53. © 2004 Wiley-Liss, Inc. [source] Defective calcium homeostasis in the cerebellum in a mouse model of Niemann,Pick A diseaseJOURNAL OF NEUROCHEMISTRY, Issue 6 2005Luba Ginzburg Abstract We recently demonstrated that calcium homeostasis is altered in mouse models of two sphingolipid storage diseases, Gaucher and Sandhoff diseases, owing to modulation of the activities of a calcium-release channel (the ryanodine receptor) and of the sarco/endoplasmic reticulum Ca2+ -ATPase (SERCA) respectively, by the accumulating sphingolipids. We now demonstrate that calcium homeostasis is also altered in a mouse model of Niemann,Pick A disease, the acid sphingomyelinase (A-SMase)-deficient mouse (ASM,/,), with reduced rates of calcium uptake via SERCA in the cerebellum of 6,7-month-old mice. However, the mechanism responsible for defective calcium homeostasis is completely different from that observed in the other two disease models. Thus, levels of SERCA expression are significantly reduced in the ASM,/, cerebellum by 6,7 months of age, immediately before death of the mice, as are levels of the inositol 1,4,5-triphosphate receptor (IP3R), the major calcium-release channel in the cerebellum. Systematic analyses of the time course of loss of SERCA and IP3R expression revealed that loss of the IP3R preceeded that of SERCA, with essentially no IP3R remaining by 4 months of age, whereas SERCA was still present even after 6 months. Expression of zebrin II (aldolase C), a protein found in about half of the Purkinje cells in the adult mouse cerebellum, was essentially unchanged during development. We discuss possible pathological mechanisms related to calcium dysfunction that may cause Purkinje cell degeneration, and as a result, the onset of neuropathology in Niemann,Pick A disease. [source] Thermochemical Sulfate Reduction in the Tazhong District, Tarim Basin, Northeast China: Evidence from Formation Water and Natural Gas GeochemistryACTA GEOLOGICA SINICA (ENGLISH EDITION), Issue 2 2010Caifu XIANG Abstract: Systematic analyses of the formation water and natural gas geochemistry in the Central Uplift of the Tarim Basin (CUTB) show that gas invasion at the late stage is accompanied by an increase of the contents of H2S and CO2 in natural gas, by the forming of the high total dissolved solids formation water, by an increase of the content of HCO,3, relative to Cl,, by an increase of the 2nd family ions (Ca2+, Mg2+, Sr2+ and Ba2+) and by a decrease of the content of SO2,4, relative to Cl,. The above phenomena can be explained only by way of thermochemical sulfate reduction (TSR). TSR often occurs in the transition zone of oil and water and is often described in the following reaction formula: ,CH+CaSO4+H- 2O,H2S+CO2+CaCO3. (1) Dissolved SO2,4 in the formation water is consumed in the above reaction, when H2S and CO2 are generated, resulting in a decrease of SO2,4 in the formation water and an increase of both H2S and CO2 in the natural gas. If formation water exists, the generated CO2 will go on reacting with the carbonate to form bicarbonate, which can be dissolved in the formation water, thus resulting in the enrichment of Ca2+ and HCO,3. The above reaction can be described by the following equation: CO2+H2O+CaCO3,Ca2++2HCO,3. The stratigraphic temperatures of the Cambrian and lower Ordovician in CUTB exceeded 120°C, which is the minimum for TSR to occur. At the same time, dolomitization, which might be a direct result of TSR, has been found in both the Cambrian and the lower Ordovician. The above evidence indicates that TSR is in an active reaction, providing a novel way to reevaluate the exploration potentials of natural gas in this district. [source] Strain localization in sand: an overview of the experimental results obtained in Grenoble using stereophotogrammetryINTERNATIONAL JOURNAL FOR NUMERICAL AND ANALYTICAL METHODS IN GEOMECHANICS, Issue 4 2004Jacques Desrues Abstract Experimental results are presented from the extensive program of drained plane strain compression tests on sand carried out in Grenoble over the last two decades. Systematic analysis of photographs of the deforming specimen allowed for measuring deformations and determining strain fields throughout the test, that is: prior to, at, and after the onset of strain localization. The principles, details and accuracy of the procedure are described, as well as its suitability to properly depict the patterns of deformation. Findings concerning the occurrence and progression of strain localization are discussed. The issues of shear band orientation and thickness are addressed, as well as temporary and persistent complex localization patterns, and the volumetric behaviour inside a band after its formation. The influence of such variables as initial state of the sand (effective stress and relative density), specimen size and slenderness, as well as grain size, is discussed. Copyright © 2004 John Wiley & Sons, Ltd [source] Fully relativistic analysis of the absorption spectra of Ca3Sc2Ge3O12:Ni2+PHYSICA STATUS SOLIDI (B) BASIC SOLID STATE PHYSICS, Issue 12 2006M. G. Brik Abstract Systematic analysis of the energy level schemes, ground state absorption (GSA) and covalency effects for the Ni2+ ion in Ca3Sc2Ge3O12 was performed. The recently developed first-principles approach to the analysis of the absorption spectra of impurity ions in crystals based on the discrete variational multi-electron method (DV-ME) [K. Ogasawara et al., Phys. Rev. B 64, 115413 (2001)] was used in the calculations. As a result, complete energy level schemes of Ni2+ and its absorption spectra at both possible crystallographic positions (distorted octahedral Sc3+ and tetrahedral Ge4+ positions) were calculated, assigned and compared with experimental data. Energies of the charge transfer (CT) transitions for both positions are estimated. Numerical contributions of all possible electron configurations into the calculated energy states were determined. By performing analysis of the molecular orbitals (MO) population, it was shown that the covalency of the chemical bonds between the Ni2+ and O2, ions increases in passing from the hexa- to the tetra-coordinated complex. (© 2006 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim) [source] Structure and hydration of the amylopectin trisaccharide building blocks,Synthesis, NMR, and molecular dynamicsBIOPOLYMERS, Issue 12 2008Peter I. Hansen Abstract To gain insight into the molecular details and hydration of amylopectin, the five constituting trisaccharides have been chemically synthesized as their methyl ,-glycosides. All five trisaccharides were subjected to 950 MHz NMR spectroscopy for complete assignment and nanosecond molecular dynamics trajectories were calculated to study the structure and dynamics of the trisaccharides in aqueous solution. Systematic analysis of the simulation data revealed several examples of bridging water molecules playing an important role in the stabilization of specific amylopectin conformations, which was also supported by the experimental NMR data such as interresidue NOE's and heteronuclear scalar couplings between nuclei from neighboring residues. Although ,-maltotriose, ,-iso-maltotriose, ,-panose and ,-isopanose are relatively well characterized structures, the study also includes one less characterized trisaccharide with the structure ,Glcp(1,4),Glcp(1,6),Glcp. This trisaccharide, tentatively labelled ,-forkose, is located at the branch point of amylopectin, forking the amylopectin into two strands that align into double-helical segments. The results show that the conformation of ,-forkose takes a natural bend form which fits well into the structure of the double-helical segment of amylopectin. As the only trisaccharide in this study the structure of ,-forkose is not significantly influenced by the hydration. In contrast, ,-isopanose takes a restricted, but rather extended form due to an exceptionally strong localized water density. The two homo-linkage oligomers, ,-maltotriose and ,-iso-maltotriose, showed to be the most extended and the most flexible trimers, respectively, providing regular structure for crystalline domains and maximum linker flexibility for amorphous domains. © 2008 Wiley Periodicals, Inc. Biopolymers 89: 1179,1193, 2008. This article was originally published online as an accepted preprint. The "Published Online" date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com [source] Single amino acid repeats in signal peptidesFEBS JOURNAL, Issue 15 2010abaj There has been an increasing interest in single amino acid repeats ever since it was shown that these are the cause of a variety of diseases. Although a systematic study of single amino acid repeats is challenging, they have subsequently been implicated in a number of functional roles. In general surveys, leucine runs were among the most frequent. In the present study, we present a detailed investigation of repeats in signal peptides of secreted and type I membrane proteins in comparison with their mature parts. We focus on eukaryotic species because single amino acid repeats are generally rather rare in archaea and bacteria. Our analysis of over 100 species shows that repeats of leucine (but not of other hydrophobic amino acids) are over-represented in signal peptides. This trend is most pronounced in higher eukaryotes, particularly in mammals. In the human proteome, although less than one-fifth of all proteins have a signal peptide, approximately two-thirds of all leucine repeats are located in these transient regions. Signal peptides are cleaved early from the growing polypeptide chain and then degraded rapidly. This may explain why leucine repeats, which can be toxic, are tolerated at such high frequencies. The substantial fraction of proteins affected by the strong enrichment of repeats in these transient segments highlights the bias that they can introduce for systematic analyses of protein sequences. In contrast to a general lack of conservation of single amino acid repeats, leucine repeats were found to be more conserved than the remaining signal peptide regions, indicating that they may have an as yet unknown functional role. [source] Risk factors for adverse events in children with colds emerging from anesthesia: a logistic regressionPEDIATRIC ANESTHESIA, Issue 2 2007J. RACHEL HOMER BM BCh Summary Background:, Recent upper respiratory infection (URI) in children increases respiratory adverse events following anesthesia for elective surgery. The increased risk continues weeks after resolution of acute URI symptoms. Few systematic analyses have explored specific risk factors. This logistic regression explores the relationship between preoperative URI symptoms and adverse events during emergence from anesthesia. Methods:, Data were combined from control groups of several prospective observational and interventional studies in elective pediatric anesthesia in a tertiary care pediatric hospital. In each study, a blinded observer, distinct from the anesthesia care team, prospectively recorded the presence of stridor, oxygen desaturations (and their duration), coughing and laryngospasm. Parents were subsequently asked about the presence of 10 cold symptoms during the 6 weeks prior to operation. Results:, Our model, based on a dataset of 335 patients, did not demonstrate an association between any particular symptoms and the rate of respiratory adverse events during emergence from anesthesia, with the exception of low-grade fever which appeared to be mildly protective. Respiratory adverse events were affected by the airway management technique (device used and timing of extubation), and adverse events were increased if peak URI symptoms had occurred within the preceding 4 weeks. Conclusions:, Specific preoperative symptoms were not useful in predicting respiratory adverse events during emergence from anesthesia. [source] The Source Provenance of Bronze Age and Roman pottery from CyprusARCHAEOMETRY, Issue 1 2002B. Gomez Archaeological interpretations of ancient economies have been strengthened by chemical analyses of ceramics, which provide the clearest evidence for economic activity, and comprise both the objects of exchange and its means. Pottery is often manufactured from local materials, but its compositional diversity typically prevents significant patterns of resource utilization from being identified. Centrally located and positioned on traditional shipping routes, Cyprus maintained ties with and supplied a variety of distinctive ceramic products to the major commercial centres in the eastern Mediterranean throughout Antiquity. We analysed two Cypriot .ne wares and a variety of utilitarian pottery, as well as samples of extant Cypriot clays to determine source provenance. These chemical analyses provide an objective indication of the origins of ancient (Bronze Age and Roman) ceramics manufactured on Cyprus. The distribution of the probable clay sources and the links between pottery style and the material environment also afford a perspective on the spatial organization of large-scale pottery production on the island. Compositional analysis provides the means to assemble geographies of pottery production and to unravel the interregional system of exchange that operated in Antiquity, but the ability to accomplish these tasks is predicated on systematic analyses of ceramic products and raw materials that are found far beyond the bounds of individual archaeological sites. [source] Calibrating conservation: new tools for measuring successCONSERVATION LETTERS, Issue 4 2008Valerie Kapos Abstract Conservation practitioners, policy makers, and donors agree that there is an urgent need to identify which conservation approaches are most likely to succeed in order to use more effectively the limited resources available for conservation. While recently developed standards of good practice in conservation are helpful, a framework for evaluation is needed that supports systematic analysis of conservation effectiveness. A conceptual framework and scorecard developed by the Cambridge Conservation Forum help to address common constraints to evaluating conservation success: unclear objectives, ineffective information management, the long time frames of conservation outcomes, scarcity of resources for evaluation, and lack of incentives for such evaluation. For seven major categories of conservation activity, the CCF tools help clarify conservation objectives and provide a standardized framework that is a useful basis for managing information about project outcomes and existing conservation experience. By identifying key outcomes that can predict conservation success and can be assessed in relatively short time frames, they help to make more efficient use of scarce monitoring and evaluation resources. With wide application, the CCF framework and evaluation tool can provide a powerful platform for drawing on the experience of past and ongoing conservation projects to identify quantitatively factors that contribute to conservation success. [source] Alignment and Alliances for Research Institutes Engaged in Product Innovation.CREATIVITY AND INNOVATION MANAGEMENT, Issue 2 2003Two Case Studies Research institutes mainly engage in product innovation for the purpose of applying, testing and usually also transferring knowledge or technology. Managing product innovation processes in this type of environment leads to various problems with the establishment and managent of alliances and alignment. In this paper a systematic analysis of product innovation at two energy research institutes is presented, paying explicit attention to the strategic alliances in terms of alignment mechanisms. The cases illustrate clearly how the research institutes manage their external networks for product innovation, allowing comparison of the strengths and weaknesses of the two research institutes, and an indication of lessons to be learned from each other. The systematic analysis contributes to the identifying of the appropriate product innovaiton objectives to be pursued through strategic alliances, as well as the determination of suitable alignment mechanisms for product innovation. Lessons learned are presented in the area of context and contingency influences, crossing organizational barriers, differences in culture and the balancing of operational effectiveness and strategic flexibility. [source] Multiple Conceptualizations of Small Business Web Use and Benefit*DECISION SCIENCES, Issue 3 2003Kurt A. Pflughoeft ABSTRACT Small businesses play an important role in the U.S. economy and there is anecdotal evidence that use of the Web is beneficial to such businesses. There is, however, little systematic analysis of the conditions that lead to successful use of and thereby benefits from the Web for small businesses. Based on the innovation adoption, organizations, and information systems (IS) implementation literature, we identify a set of variables that are related to adoption, use, and benefits of information technology (IT), with particular emphasis on small businesses. These variables are reflective of an organization's contextual characteristics, its IT infrastructure, Web use, and Web benefits. Since the extant research does not suggest a single theoretical model for Web use and benefits in the context of small businesses, we adopt a modeling approach and explore the relationships between "context-IT-use-benefit" (CIUB) through three models,partial-mediator, reduced partial-mediator, and mediator. These models posit that the extent of Web use by small businesses and the associated benefits are driven by organizations' contextual characteristics and their IT infrastructure. They differ in the endogeneity/exogeneity of the extent of IT sophistication, and in the direct/mediated effects of organizational context. We examine whether the relationships between variables identified in the literature hold within the context of these models using two samples of small businesses with national coverage, including various sizes, and representing several industry sectors. The results show that the evidence for patterns of relationships is similar across the two independent samples for two of these models. We highlight the relationships within the reduced partial-mediator and mediator models for which conclusive evidence are given by both samples. Implications for small business managers and providers of Web-based technologies are discussed. [source] Tactile responses of hindpaw, forepaw and whisker neurons in the thalamic ventrobasal complex of anesthetized ratsEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 2 2008J. Aguilar Abstract The majority of studies investigating responses of thalamocortical neurons to tactile stimuli have focused on the whisker representation of the rat thalamus: the ventral,posterior,medial nucleus (VPM). To test whether the basic properties of thalamocortical responses to tactile stimuli could be extended to the entire ventrobasal complex, we recorded single neurons from the whisker, forepaw and hindpaw thalamic representations. We performed a systematic analysis of responses to stereotyped tactile stimuli , 500 ms pulses (i.e. ON,OFF stimuli) or 1 ms pulses (i.e. impulsive stimuli) , under two different anesthetics (pentobarbital or urethane). We obtained the following main results: (i) the tuning of cells to ON vs. OFF stimuli displayed a gradient across neurons, so that two-thirds of cells responded more to ON stimuli and one-third responded more to OFF stimuli; (ii) on average, response magnitudes did not differ between ON and OFF stimuli, whereas latencies of response to OFF stimuli were a few milliseconds longer; (iii) latencies of response to ON and OFF stimuli were highly correlated; (iv) responses to impulsive stimuli and ON stimuli showed a strong correlation, whereas the relationship between the responses to impulsive stimuli and OFF stimuli was subtler; (v) unlike ON responses, OFF responses did not decrease when stimuli were moved from the receptive field center to a close location in the excitatory surround. We obtained the same results for hindpaw, forepaw and whisker neurons. Our results support the view of a neurophysiologically homogeneous ventrobasal complex, in which OFF responses participate in the structure of the spatiotemporal receptive field of thalamocortical neurons for tactile stimuli. [source] Auxiliary subunit regulation of high-voltage activated calcium channels expressed in mammalian cellsEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 1 2004Takahiro Yasuda Abstract The effects of auxiliary calcium channel subunits on the expression and functional properties of high-voltage activated (HVA) calcium channels have been studied extensively in the Xenopus oocyte expression system, but are less completely characterized in a mammalian cellular environment. Here, we provide the first systematic analysis of the effects of calcium channel , and ,2,, subunits on expression levels and biophysical properties of three different types (Cav1.2, Cav2.1 and Cav2.3) of HVA calcium channels expressed in tsA-201 cells. Our data show that Cav1.2 and Cav2.3 channels yield significant barium current in the absence of any auxiliary subunits. Although calcium channel , subunits were in principle capable of increasing whole cell conductance, this effect was dependent on the type of calcium channel ,1 subunit, and ,3 subunits altogether failed to enhance current amplitude irrespective of channel subtype. Moreover, the ,2,, subunit alone is capable of increasing current amplitude of each channel type examined, and at least for members of the Cav2 channel family, appears to act synergistically with , subunits. In general agreement with previous studies, channel activation and inactivation gating was regulated both by , and by ,2,, subunits. However, whereas pronounced regulation of inactivation characteristics was seen with the majority of the auxiliary subunits, effects on voltage dependence of activation were only small (< 5 mV). Overall, through a systematic approach, we have elucidated a previously underestimated role of the ,2,,1 subunit with regard to current enhancement and kinetics. Moreover, the effects of each auxiliary subunit on whole cell conductance and channel gating appear to be specifically tailored to subsets of calcium channel subtypes. [source] Synthesis and Mass Spectrometric Analysis of CyclostellettaminesH, I, K and LEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 5 2006Achim Grube Abstract Very recently the new cyclostellettamines H, I, K and L were identified from a Brazilian sponge of the genus Pachychalina. They were isolated together with the known cyclostellettamines A,G in a mixture of only 1.5 mg. To obtain further material for biological investigations, the synthesis of the four new cyclostellettamines has been carried out. Since mass spectrometry plays an essential role in identifying these compounds a systematic analysis of the cyclostellettamines is discussed. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006) [source] Correlation of psoriasis activity with abundance of CD25+CD8+ T cells: conditions for cloning T cells from psoriatic plaquesEXPERIMENTAL DERMATOLOGY, Issue 10 2004Wayan M. Kohlmann Abstract:, The role of T cells in the pathogenesis of psoriasis is widely acknowledged. However, key aspects of their precise function in the disease as well as the relative pathogenic contribution of T-cell subsets are still unknown. T-cell clones have been isolated from psoriatic plaques but a study of conditions affecting the isolation and expansion of T-cell clones from psoriatic skin has not been reported to date. Here, we observe a correlation of disease activity with the frequency of the CD3+CD8+CD25+ subset. We show that prolonged in vitro culture changes the phenotypic subset distribution of T-cell lines derived from psoriatic skin and that T-cell clones can be isolated by sorting of CD25+ cells emigrated from skin fragments after 7 days. We evaluate various conditions affecting expansion of psoriatic T-cell clones in vitro and show that blocking apoptosis can facilitate proliferation of activated T-cell clones in vitro. Our results indicate a prominent role of the CD8+CD25+ T-cell subset in disease pathogenesis and should be useful in the design of experiments aiming at a systematic analysis of the specificity of clones present in psoriatic plaques. [source] Numerical investigation on J -integral testing of heterogeneous fracture toughness testing specimens: Part I , weld metal cracksFATIGUE & FRACTURE OF ENGINEERING MATERIALS AND STRUCTURES, Issue 8 2003Y.-J. KIM ABSTRACT Based on extensive two-dimensional (2D) finite element (FE) analyses, the present work provides the plastic , factor solutions for fracture toughness J -integral testing of heterogeneous specimens with weldments. Solutions cover practically interesting ranges of strength mismatch and relative weld width, and are given for three typical geometries for toughness testing: a middle cracked tension (M(T)) specimen, single edge cracked bend (SE(B)) specimen and (C(T)) specimen. For mismatched M(T) specimens, both plane strain and plane stress conditions are considered, whereas for SE(B) and C(T) specimens, only the plane strain condition is considered. For all cases, only deep cracks are considered, and an idealized butt weld configuration is considered, where the weld metal strip has a rectangular cross section. Based on the present solutions for the strength mismatch effect on plastic , factors, a window is provided, within which the homogeneous J estimation procedure can be used for weldment toughness testing. The effect of the weld groove configuration on the plastic , factor is briefly discussed, concluding the need for further systematic analysis to provide guidance to practical toughness testing. [source] Analysis of DNA-binding sites on Mhr1, a yeast mitochondrial ATP-independent homologous pairing proteinFEBS JOURNAL, Issue 6 2010Tokiha Masuda The Mhr1 protein is necessary for mtDNA homologous recombination in Saccharomyces cerevisiae. Homologous pairing (HP) is an essential reaction during homologous recombination, and is generally catalyzed by the RecA/Rad51 family of proteins in an ATP-dependent manner. Mhr1 catalyzes HP through a mechanism similar, at the DNA level, to that of the RecA/Rad51 proteins, but without utilizing ATP. However, it has no sequence homology with the RecA/Rad51 family proteins or with other ATP-independent HP proteins, and exhibits different requirements for DNA topology. We are interested in the structural features of the functional domains of Mhr1. In this study, we employed the native fluorescence of Mhr1's Trp residues to examine the energy transfer from the Trp residues to etheno-modified ssDNA bound to Mhr1. Our results showed that two of the seven Trp residues (Trp71 and Trp165) are spatially close to the bound DNA. A systematic analysis of mutant Mhr1 proteins revealed that Asp69 is involved in Mg2+ -dependent DNA binding, and that multiple Lys and Arg residues located around Trp71 and Trp165 are involved in the DNA-binding activity of Mhr1. In addition, in vivo complementation analyses showed that a region around Trp165 is important for the maintenance of mtDNA. On the basis of these results, we discuss the function of the region surrounding Trp165. [source] Prediction of protein structural class by amino acid and polypeptide compositionFEBS JOURNAL, Issue 17 2002Rui-yan Luo A new approach of predicting structural classes of protein domain sequences is presented in this paper. Besides the amino acid composition, the composition of several dipeptides, tripeptides, tetrapeptides, pentapeptides and hexapeptides are taken into account based on the stepwise discriminant analysis. The result of jackknife test shows that this new approach can lead to higher predictive sensitivity and specificity for reduced sequence similarity datasets. Considering the dataset PDB40-B constructed by Brenner and colleagues, 75.2% protein domain sequences are correctly assigned in the jackknife test for the four structural classes: all-,, all-,, ,/, and , + ,, which is improved by 19.4% in jackknife test and 25.5% in resubstitution test, in contrast with the component-coupled algorithm using amino acid composition alone (AAC approach) for the same dataset. In the cross-validation test with dataset PDB40-J constructed by Park and colleagues, more than 80% predictive accuracy is obtained. Furthermore, for the dataset constructed by Chou and Maggiona, the accuracy of 100% and 99.7% can be easily achieved, respectively, in the resubstitution test and in the jackknife test merely taking the composition of dipeptides into account. Therefore, this new method provides an effective tool to extract valuable information from protein sequences, which can be used for the systematic analysis of small or medium size protein sequences. The computer programs used in this paper are available on request. [source] Molecular interactions of fission yeast Skp1 and its role in the DNA damage checkpointGENES TO CELLS, Issue 5 2004Anna Lehmann Skp1 is a central component of the E3 ubiquitin ligase SCF (Skp1-Cullin-1- F -box). It forms an adapter bridge between Cullin-1 and the substrate-determining component, the F-box protein. In order to establish the role of Skp1, a temperature sensitive (ts) screen was carried out using mutagenic PCR (polymerase chain reaction) and 9 independent ts mutants were isolated. Mapping the mutated residues on the 3-D structure of human Skp1 suggested that the mutants would be compromised in binding to F-box proteins but not Cullin-1 (Pcu1). In order to assess the binding properties of ts Skp1, 12 F-box proteins and Pcu1 were epitope-tagged, and co-immunoprecipitation performed. This systematic analysis showed that ts Skp1 retains binding to Pcu1. However, binding to three specific F-box proteins, essential Pof1, Pof3 involved in maintaining genome integrity, and nonessential Pof10, was reduced. skp1ts cells exhibit a G2 cell cycle delay, which is attributable to activation of the DNA damage checkpoint. Intriguingly, contrary to pof3 mutants, in which this checkpoint is required for survival, checkpoint abrogation in skp1ts suppresses a G2 delay and furthermore almost rescues the ts phenotype. The activation mechanism of the DNA damage checkpoint therefore differs between pof3, and skp1ts, implicating a novel role for Skp1 in the checkpoint-signalling cascade. [source] Expression and mutational analysis of MET in human solid cancersGENES, CHROMOSOMES AND CANCER, Issue 12 2008Patrick C. Ma MET receptor tyrosine kinase and its ligand hepatocyte growth factor (HGF) regulate a variety of cellular functions, many of which can be dysregulated in human cancers. Activated MET signaling can lead to cell motility and scattering, angiogenesis, proliferation, branching morphogenesis, invasion, and eventual metastasis. We performed systematic analysis of the expression of the MET receptor and its ligand HGF in tumor tissue microarrays (TMA) from human solid cancers. Standard immunohistochemistry (IHC) and a computerized automated scoring system were used. DNA sequencing for MET mutations in both nonkinase and kinase domains was also performed. MET was differentially overexpressed in human solid cancers. The ligand HGF was widely expressed in both tumors, primarily intratumoral, and nonmalignant tissues. The MET/HGF likely is functional and may be activated in autocrine fashion in vivo. MET and stem cell factor (SCF) were found to be positively stained in the bronchioalevolar junctions of lung tumors. A number of novel mutations of MET were identified, particularly in the extracellular semaphorin domain and the juxtamembrane domain. MET-HGF pathway can be assayed in TMAs and is often overexpressed in a wide variety of human solid cancers. MET can be activated through overexpression, mutation, or autocrine signaling in malignant cells. Mutations in the nonkinase regions of MET might play an important role in tumorigenesis and tumor progression. MET would be an important therapeutic antitumor target to be inhibited, and in lung cancer, MET may represent a cancer early progenitor cell marker. © 2008 Wiley-Liss, Inc. [source] Lafora disease in the Indian population: EPM2A and NHLRC1 gene mutations and their impact on subcellular localization of laforin and malin,HUMAN MUTATION, Issue 6 2008Shweta Singh Abstract Lafora disease (LD) is a fatal form of teenage-onset autosomal recessive progressive myoclonus epilepsy. LD is more common among geographic isolates and in populations with a higher rate of consanguinity. Mutations in two genes, EPM2A encoding laforin phosphatase, and NHLRC1 encoding malin ubiquitin ligase, have been shown to cause the LD. We describe here a systematic analysis of the EPM2A and the NHLRC1 gene sequences in 20,LD families from the Indian population. We identified 12 distinct mutations in 15,LD families. The identified novel mutations include 4 missense mutations (K140N, L310W, N148Y, and E210,K) and a deletion of exon 3 for EPM2A, and 4 missense mutations (S22R, L279P, L279P, and L126P) and a single base-pair insertional mutation (612insT) for NHLRC1. The EPM2A gene is known to encode two laforin isoforms having distinct carboxyl termini; a major isoform localized in the cytoplasm, and a minor isoform that targeted the nucleus. We show here that the effect of the EPM2A gene mutation L310W was limited to the cytoplasmic isoform of laforin, and altered its subcellular localization. We have also analyzed the impact of NHLRC1 mutations on the subcellular localization of malin. Of the 6 distinct mutants tested, three targeted the nucleus, one formed perinuclear aggregates, and two did not show any significant difference in the subcellular localization as compared to the wild-type malin. Our results suggest that the altered subcellular localization of mutant proteins of the EPM2A and NHLRC1 genes could be one of the molecular bases of the LD phenotype. © 2008 Wiley-Liss, Inc. [source] Impact of mutant p53 functional properties on TP53 mutation patterns and tumor phenotype: lessons from recent developments in the IARC TP53 database,,HUMAN MUTATION, Issue 6 2007Audrey Petitjean Abstract The tumor suppressor gene TP53 is frequently mutated in human cancers. More than 75% of all mutations are missense substitutions that have been extensively analyzed in various yeast and human cell assays. The International Agency for Research on Cancer (IARC) TP53 database (www-p53.iarc.fr) compiles all genetic variations that have been reported in TP53. Here, we present recent database developments that include new annotations on the functional properties of mutant proteins, and we perform a systematic analysis of the database to determine the functional properties that contribute to the occurrence of mutational "hotspots" in different cancer types and to the phenotype of tumors. This analysis showed that loss of transactivation capacity is a key factor for the selection of missense mutations, and that difference in mutation frequencies is closely related to nucleotide substitution rates along TP53 coding sequence. An interesting new finding is that in patients with an inherited missense mutation, the age at onset of tumors was related to the functional severity of the mutation, mutations with total loss of transactivation activity being associated with earlier cancer onset compared to mutations that retain partial transactivation capacity. Furthermore, 80% of the most common mutants show a capacity to exert dominant-negative effect (DNE) over wild-type p53, compared to only 45% of the less frequent mutants studied, suggesting that DNE may play a role in shaping mutation patterns. These results provide new insights into the factors that shape mutation patterns and influence mutation phenotype, which may have clinical interest. Hum Mutat 28(6), 622,629, 2007. Published 2007 Wiley-Liss, Inc. [source] Negotiating European Works Councils: contours of constrained choiceINDUSTRIAL RELATIONS JOURNAL, Issue 1 2002Mark Gilman This paper presents a systematic analysis of the factors influencing the nature of the ,constrained choices' being made by management and employee representatives in concluding agreements establishing EWCs. Four influences,a ,statutory model effect'; a ,learning effect'; a ,country effect'; and a ,sector effect',are found to be at work. [source] An innovative approach to the theory and practice of organizational analysis: my journey with Elliott JaquesINTERNATIONAL JOURNAL OF APPLIED PSYCHOANALYTIC STUDIES, Issue 4 2005Aldo Schlemenson Abstract This article highlights the author's experience working with Elliott Jaques and his theory for over 35 years in Argentina. It examines the development of Jaques' theoretical approach to organizational theory over two decades, transforming from a psychological to a social theoretical framework. Emphasis is put in the notions of the organizational structure, the hierarchical managerial system, stratification, and the managerial accountability in a manner that allows for a systematic analysis. The "time-span of discretion" instrument is the means for evaluating jobs and for having access to extant organization. This approach allows a process of change combining effectiveness with a humanistic democratization of the workplace and ethics. This article provides examples of projects implemented in the public administration area, verifying the consistency of the theory and its practical applications, in particular concerning individual capabilities, the talent pool, and their evaluation. It contains a Foreword by Dr Carlos Silvani, International Monetary Fund, Washington, D.C. Copyright © 2005 John Wiley & Sons, Ltd. [source] The North Atlantic Oscillation and European vegetation dynamicsINTERNATIONAL JOURNAL OF CLIMATOLOGY, Issue 14 2008Célia Gouveia Abstract The relationship between vegetation greenness and the North Atlantic Oscillation (NAO) is assessed over Europe. The study covers the 21-year period from 1982 to 2002 and is based on monthly composites of the Normalised Difference Vegetation Index (NDVI) and Brightness Temperature from the Global Inventory Monitoring and Modelling System (GIMMS) as well as on monthly precipitation from the Global Precipitation Climatology Centre (GPCC). A systematic analysis is first performed of point correlation fields over the 21-year period between the winter NAO index and spring and summer NDVI, followed by an assessment of the vegetation response to precipitation and temperature conditions in winter, over two contrasting regions, namely the Iberian Peninsula and Northeastern Europe. Finally, the impact of NAO on vegetation dynamics over the two regions is evaluated by studying the corresponding annual cycles of NDVI and comparing their behaviour for years associated with opposite NAO phases. Over the Iberian Peninsula there is strong evidence that positive (negative) values of winter NAO induce low (high) vegetation activity in the following spring and summer seasons. This feature is mainly associated with the impact of NAO on winter precipitation, together with the strong dependence of spring and summer NDVI on water availability during the previous winter. Northeastern Europe shows a different behaviour, with positive (negative) values of winter NAO inducing high (low) values of NDVI in spring, but low (high) values of NDVI in summer. This behaviour mainly results from the strong impact of NAO on winter temperature, associated with the critical dependence of vegetation growth on the combined effect of warm conditions and water availability during the winter season. Copyright © 2008 Royal Meteorological Society [source] | |||||||||||||||||||||||||||||||||||||||||||||||||