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Discovery
Kinds of Discovery Terms modified by Discovery Selected AbstractsCASTING THE RIACE BRONZES (2): A SCULPTOR's DISCOVERYOXFORD JOURNAL OF ARCHAEOLOGY, Issue 4 2004NIGEL KONSTAM Summary. The discovery presented in this paper may reshape the stylistic history of Greek art. It is that the torso and limbs of the Riace Bronzes were cast from life, rather than having been previously modelled in clay. [source] THE DISCOVERY OF AN ANGLO-SAXON GRUBENHAUS AT NEW BEWICK, NORTHERN UK USING ELECTRICAL SURVEYING AND PREDICTIVE DECONVOLUTIONARCHAEOMETRY, Issue 2 2010P. W. J. GLOVER Twin-probe and 33-fold multiplexed Wenner electrical resistivity surveys were carried out at New Bewick, northern UK to examine the extent of crop marks and potential Grubenhäuser (sunken-featured buildings, sunken-floored buildings or SFBs). The twin-probe method was faster, but provided data with a lower spatial resolution. However, the Wenner array data was affected by characteristic ,M'- or ,W'-shaped responses over filled excavations such as those expected to represent a Grubenhaus. The raw Wenner array data have been analysed using one-dimensional and two-dimensional predictive deconvolution in order to remove these artefacts. The deconvolution was carried out using an inverse matrix element method. The filtered results indicate the presence of anomalies consistent with the presence of at least six Grubenhäuser and other anomalies concurrent with the linear crop-marks. One particular anomaly measured about 5 m by 4 m and with a pit depth of 0.6 m below 0.3 m of topsoil. This anomaly was subsequently excavated and a Grubenhaus was discovered at the site. The excavated Grubenhaus measured 4.7 m by 3.9 m with a pit depth of 0.5 m below the base of the topsoil, confirming the electrical survey results. [source] DARK AND SHINY: THE DISCOVERY OF CHROMITE IN BRONZE AGE FAIENCE*ARCHAEOMETRY, Issue 2 2006N. C. F. GROOT The Late Bronze Age (1550,1200 bc) in the Near East was a period of cultural development, international trade and technological innovation, notably in metallurgy and silicate technology. As a spin-off of the new glass technology, new colorants were also applied to faience glazes presumably to increase their aesthetic value. Here, we report on the presence of chromite minerals in the glaze of a faience vessel from Deir ,Alla, Jordan, 1200 years earlier than reported so far. Importantly, chromite was not only used as a greyish pigment, but also as a nucleating agent for spherulitic crystallization of augite in the amorphous glaze. These synthetic augite formations give a unique, sparkly appearance to the faience vessel, apparently imitating a metallic look. The making of such an intricate glaze and its contemporary significance reflect not only the high level but also the appreciation of innovation in that region at that time. [source] THERAPY AS MEMORY-WORK: DILEMMAS OF DISCOVERY, RECOVERY AND CONSTRUCTIONBRITISH JOURNAL OF PSYCHOTHERAPY, Issue 4 2002Erica Burman ABSTRACT In this paper I have sought to shift the focus on the construction of memory within psychotherapeutic practice in a number of different directions to draw some more general lessons for the process and status of therapeutic accounts. The precipitating context for the current scrutiny of memory-making within therapy may have limited its scope and fruitfulness. The fact that this issue was largely prompted by debates about the status of (usually) adult women's recovery of memories of early abuse within therapy is a relevant factor that has been compounded by issues of professional credibility and hierarchy. Clearly, at a cultural level, women's memories of childhood abuse function politically as well as personally, as reflected by the social and legal responses to this challenge. However, guidelines for professional practice cannot legislate for the indeterminacies surrounding the subjectivity of memory, while assumptions underlying the empirical psychological resources drawn upon to inform debates in psychotherapy require critical scrutiny. Clinical and interpretive dilemmas extend beyond the status accorded client memorial reports to therapists' memory-making practices as textualized via both supervision and clinical notetaking. Drawing on more recent (including feminist) discussions of memory that identify different political possibilities within third and first person accounts it was suggested that, rather than eschewing the subjectivity of memory, therapists can instead analyse this as a key interpretive and reflexive resource to inform their own practice. [source] EFFICIENT MARKOV NETWORK DISCOVERY USING PARTICLE FILTERSCOMPUTATIONAL INTELLIGENCE, Issue 4 2009Dimitris Margaritis In this paper, we introduce an efficient independence-based algorithm for the induction of the Markov network (MN) structure of a domain from the outcomes of independence test conducted on data. Our algorithm utilizes a particle filter (sequential Monte Carlo) method to maintain a population of MN structures that represent the posterior probability distribution over structures, given the outcomes of the tests performed. This enables us to select, at each step, the maximally informative test to conduct next from a pool of candidates according to information gain, which minimizes the cost of the statistical tests conducted on data. This makes our approach useful in domains where independence tests are expensive, such as cases of very large data sets and/or distributed data. In addition, our method maintains multiple candidate structures weighed by posterior probability, which allows flexibility in the presence of potential errors in the test outcomes. [source] From HLA-B27 to spondyloarthritis: a journey through the ERIMMUNOLOGICAL REVIEWS, Issue 1 2010Robert A. Colbert Summary:, Almost four decades of research into the role of human leukocyte antigen-B27 (HLA-B27) in susceptibility to spondyloarthritis has yet to yield a convincing answer. New results from an HLA-B27 transgenic rat model now demonstrate quite convincingly that CD8+ T cells are not required for the inflammatory phenotype. Discoveries that the HLA-B27 heavy chain has a tendency to misfold during the assembly of class I complexes in the endoplasmic reticulum (ER) and to form aberrant disulfide-linked dimers after transport to the cell surface have forced the generation of new ideas about its role in disease pathogenesis. In transgenic rats, HLA-B27 misfolding generates ER stress and leads to activation of the unfolded protein response, which dramatically enhances the production of interleukin-23 (IL-23) in response to pattern recognition receptor agonists. These findings have led to the discovery of striking T-helper 17 cell activation and expansion in this animal model, consistent with results emerging from humans with spondyloarthritis and the discovery of IL23R as an additional susceptibility gene for ankylosing spondylitis. Together, these results suggest a novel link between HLA-B27 and the T-helper 17 axis through the consequences of protein misfolding and open new avenues of investigation as well as identifying new targets for therapeutic intervention in this group of diseases. [source] The 2005 Remote-Sensing Survey of the South-Eastern Bozburun Peninsula, Turkey: Shipwreck Discoveries and their AnalysesINTERNATIONAL JOURNAL OF NAUTICAL ARCHAEOLOGY, Issue 2 2006Jeffrey G. Royal During a month-long survey of the coastline along the south-eastern Bozburun peninsula, Turkey, nine shipwreck sites were discovered. Of these, five have historical significance and represent a chronological range from the Roman Imperial to Renaissance periods. This article provides a description of the sites and associated artefacts, and attempts a provisional analysis for each wreck's operational date as well as the nature of the finds in their historical context. © 2006 The Author [source] Minds Behind the Brain: A History of the Pioneers and their Discoveries.JOURNAL OF ANATOMY, Issue 3 2000By STANLEY FINGER. (Pp. xii, illustrated; $35 hardback; ISBN 0 19 508571 X.) New York: Oxford University Press. First page of article [source] Recent Discoveries on the Control of Gonadotrophin-Releasing Hormone Neurones in Nonhuman PrimatesJOURNAL OF NEUROENDOCRINOLOGY, Issue 7 2010E. Terasawa Since Ernst Knobil proposed the concept of the gonadotrophin-releasing hormone (GnRH) pulse-generator in the monkey hypothalamus three decades ago, we have made significant progress in this research area with cellular and molecular approaches. First, an increase in pulsatile GnRH release triggers the onset of puberty. However, the question of what triggers the pubertal increase in GnRH is still unclear. GnRH neurones are already mature before puberty but GnRH release is suppressed by a tonic GABA inhibition. Our recent work indicates that blocking endogenous GABA inhibition with the GABAA receptor blocker, bicuculline, dramatically increases kisspeptin release, which plays an important role in the pubertal increase in GnRH release. Thus, an interplay between the GABA, kisspeptin, and GnRH neuronal systems appears to trigger puberty. Second, cultured GnRH neurones derived from the olfactory placode of monkey embryos exhibit synchronised intracellular calcium, [Ca2+]i, oscillations and release GnRH in pulses at approximately 60-min intervals after 14 days in vitro (div). During the first 14 div, GnRH neurones undergo maturational changes from no [Ca2+]i oscillations and little GnRH release to the fully functional state. Recent work also shows GnRH mRNA expression increases during in vitro maturation. This mRNA increase coincides with significant demethylation of a CpG island in the GnRH 5,-promoter region. This suggests that epigenetic differentiation occurs during GnRH neuronal maturation. Third, oestradiol causes rapid, direct, excitatory action in GnRH neurones and this action of oestradiol appears to be mediated through a membrane receptor, such as G-protein coupled receptor 30. [source] New Discoveries of Poll Books,PARLIAMENTARY HISTORY, Issue 3 2005EDMUND M. GREEN First page of article [source] Discoveries of Neolithic prehistoric sites at Pleistocene carbonate rock shelters on the east coast of the UAEARABIAN ARCHAEOLOGY AND EPIGRAPHY, Issue 2 2006Cajus G. Diedrich Dr.Article first published online: 8 DEC 200 Three newly discovered prehistoric sites on the east coast of the United Emirates (UAE) are described. All are located on surfaces of Pleistocene carbonates or rock shelters that are generally rare along the eastern coast of the Gulf of Oman. Aqqah 1 (Le Meridien al Aqqah Beach Resort), the most important and best preserved of these sites, is a partially collapsed rock shelter with an exposed section, lithic finds and marine molluscs. Deriving an exact date from the material present is difficult because of a lack of comparanda. A bifacial fletched arrowhead made of yellow jasper and the lithic debris of five different raw materials as well as an undecorated ceramic fragment might suggest a date in the Late Neolithic or Early Bronze Age. The presence of many marine bivalves and snails with operculae, which differ from recent coastal species, indicates the collection and consumption of living molluscs by the prehistoric population of Aqqah. Nearby burials may be related to the rock shelters. [source] Controlling False Discoveries in Multidimensional Directional Decisions, with Applications to Gene Expression Data on Ordered CategoriesBIOMETRICS, Issue 2 2010Wenge Guo Summary Microarray gene expression studies over ordered categories are routinely conducted to gain insights into biological functions of genes and the underlying biological processes. Some common experiments are time-course/dose-response experiments where a tissue or cell line is exposed to different doses and/or durations of time to a chemical. A goal of such studies is to identify gene expression patterns/profiles over the ordered categories. This problem can be formulated as a multiple testing problem where for each gene the null hypothesis of no difference between the successive mean gene expressions is tested and further directional decisions are made if it is rejected. Much of the existing multiple testing procedures are devised for controlling the usual false discovery rate (FDR) rather than the mixed directional FDR (mdFDR), the expected proportion of Type I and directional errors among all rejections. Benjamini and Yekutieli (2005,,Journal of the American Statistical Association,100, 71,93) proved that an augmentation of the usual Benjamini,Hochberg (BH) procedure can control the mdFDR while testing simple null hypotheses against two-sided alternatives in terms of one-dimensional parameters. In this article, we consider the problem of controlling the mdFDR involving multidimensional parameters. To deal with this problem, we develop a procedure extending that of Benjamini and Yekutieli based on the Bonferroni test for each gene. A proof is given for its mdFDR control when the underlying test statistics are independent across the genes. The results of a simulation study evaluating its performance under independence as well as under dependence of the underlying test statistics across the genes relative to other relevant procedures are reported. Finally, the proposed methodology is applied to a time-course microarray data obtained by Lobenhofer et al. (2002,,Molecular Endocrinology,16, 1215,1229). We identified several important cell-cycle genes, such as DNA replication/repair gene MCM4 and replication factor subunit C2, which were not identified by the previous analyses of the same data by Lobenhofer et al. (2002) and Peddada et al. (2003,,Bioinformatics,19, 834,841). Although some of our findings overlap with previous findings, we identify several other genes that complement the results of Lobenhofer et al. (2002). [source] Discoveries in Charcot,Marie,Tooth disease, Crohn's disease and Bardet,Biedl syndrome 4CLINICAL GENETICS, Issue 3 2001Simon Warby No abstract is available for this article. [source] Web Discovery and Filtering Based on Textual Relevance Feedback LearningCOMPUTATIONAL INTELLIGENCE, Issue 2 2003Wai Lam We develop a new approach for Web information discovery and filtering. Our system, called WID, allows the user to specify long-term information needs by means of various topic profile specifications. An entire example page or an index page can be accepted as input for the discovery. It makes use of a simulated annealing algorithm to automatically explore new Web pages. Simulated annealing algorithms possess some favorable properties to fulfill the discovery objectives. Information retrieval techniques are adopted to evaluate the content-based relevance of each page being explored. The hyperlink information, in addition to the textual context, is considered in the relevance score evaluation of a Web page. WID allows users to provide three forms of the relevance feedback model, namely, the positive page feedback, the negative page feedback, and the positive keyword feedback. The system is domain independent and does not rely on any prior knowledge or information about the Web content. Extensive experiments have been conducted to demonstrate the effectiveness of the discovery performance achieved by WID. [source] KDDML-G: a grid-enabled knowledge discovery systemCONCURRENCY AND COMPUTATION: PRACTICE & EXPERIENCE, Issue 13 2007Andrea Romei Abstract KDDML-G is a middleware language and system for knowledge discovery on the grid. The challenge that motivated the development of a grid-enabled version of the ,standalone' KDDML (Knowledge Discovery in Databases Markup Language) environment was on one side to exploit the parallelism offered by the grid environment, and on the other side to overcome the problem of data immovability, a quite frequent restriction on real-world data collections that has principally a privacy-preserving purpose. The last question is addressed by moving the code and ,mining' the data ,on the place', that is by adapting the computation to the availability and localization of the data. Copyright © 2007 John Wiley & Sons, Ltd. [source] Plug-and-play remote portlet publishingCONCURRENCY AND COMPUTATION: PRACTICE & EXPERIENCE, Issue 12 2007X. D. Wang Abstract Web Services for Remote Portlets (WSRP) is gaining attention among portal developers and vendors to enable easy development, increased richness in functionality, pluggability, and flexibility of deployment. Whilst currently not supporting all WSRP functionalities, open-source portal frameworks could in future use WSRP Consumers to access remote portlets found from a WSRP Producer registry service. This implies that we need a central registry for the remote portlets and a more expressive WSRP Consumer interface to implement the remote portlet functions. This paper reports on an investigation into a new system architecture, which includes a Web Services repository, registry, and client interface. The Web Services repository holds portlets as remote resource producers. A new data structure for expressing remote portlets is found and published by populating a Universal Description, Discovery and Integration (UDDI) registry. A remote portlet publish and search engine for UDDI has also been developed. Finally, a remote portlet client interface was developed as a Web application. The client interface supports remote portlet features, as well as window status and mode functions. Copyright © 2007 John Wiley & Sons, Ltd. [source] The LEAD Portal: a TeraGrid gateway and application service architectureCONCURRENCY AND COMPUTATION: PRACTICE & EXPERIENCE, Issue 6 2007Marcus Christie Abstract The Linked Environments for Atmospheric Discovery (LEAD) Portal is a science application portal designed to enable effective use of Grid resources in exploring mesoscale meteorological phenomena. The aim of the LEAD Portal is to provide a more productive interface for doing experimental work by the meteorological research community, as well as bringing weather research to a wider class of users, meaning pre-college students in grades 6,12 and undergraduate college students. In this paper, we give an overview of the LEAD project and the role that LEAD portal is playing in reaching its goals. We then describe the various technologies we are using to bring powerful and complex scientific tools to educational and research users. These technologies,a fine-grained capability based authorization framework, an application service factory toolkit, and a Web services-based workflow execution engine and supporting tools,enable our team to deploy these once inaccessible, stovepipe scientific codes onto a Grid where they can be collectively utilized. Copyright © 2006 John Wiley & Sons, Ltd. [source] Species Discovery versus Species Identification in DNA Barcoding Efforts: Response to RubinoffCONSERVATION BIOLOGY, Issue 5 2006ROB DeSALLE No abstract is available for this article. [source] The Late Prehistoric,Early Historic Game Sink in the Northwestern United StatesCONSERVATION BIOLOGY, Issue 1 2002R. Lee Lyman The number of big game killed by the Corps of Discovery in 1805,1806 and recorded by Lewis and Clark suggests that ungulates were abundant in central and eastern Montana and rare in western Montana, central Idaho, and southeastern Washington during the early nineteenth century. Paleoecologists Paul Martin and Chris Szuter conclude that this difference was a function of human predation. They support their conclusion that ungulates would have been abundant in southeastern Washington had humans not hunted them by arguing that the nineteenth-century livestock industry was successful without supplemental feeding. The livestock industry was, however, not consistently successful until artificial feeding was initiated. Archaeological data from eastern Washington indicate that ungulates have been taken by human hunters more frequently than small-mammal prey throughout the last 10,000 years and that ungulates decreased relative to small mammals coincident with changes in climate. Bison ( Bison bison) and elk (Cervus canadensis) were present in eastern Washington throughout the Holocene, but bison were abundant there only during a cooler and moister period; elk have been abundant only in the twentieth century, subsequent to transplants and the extermination of predators. Geographic variation in the abundance of bison across Montana, Idaho, and eastern Washington has been influenced by human predation but has also been influenced by biogeographic history, habitat differences, and climatic change. Resumen: Los datos históricos proveen información valiosa sobre las estructuras de los ecosistemas, sus funciones y procesos. El número de animales de caza grandes que fueron sacrificados por las tropas de descubrimiento en 1805-1806 y registradas por Lewis y Clark sugieren que los ungulados eran abundantes en Montana central y oriental y raros en Montana occidental, Idaho central y el sudeste de Washington durante los inicios del siglo diecinueve. Los paleontólogos Paul Martin y Chris Szuter concluyen que esta diferencia fue causada por la depredación humana. Ellos apoyan su conclusión de que los ungulados podrían haber sido abundantes en el sudeste de Washington si los humanos no los hubieran cazado argumentando que la industria de la ganadería del siglo diecinueve exitosa sin alimento suplementario. Sin embargo, la industria de la ganadería no fue consistentemente exitosa hasta que se inició la alimentación artificial. Los datos arqueológicos de Washington oriental indican que los ungulados fueron eliminados por los cazadores humanos mas frecuentemente que las presas pequeñas de mamíferos a lo largo de los últimos 10,000 años y que la disminución de ungulados, relativa a la de mamíferos pequeños coincidió con cambios en el clima. El bisonte (Bison bison) y el alce (Cervus canadiensis) estuvieron presentes en Washington oriental a lo largo del Holoceno, pero los bisontes fueron abundantes solo durante un periodo mas frío y húmedo; los alces habían sido abundantes solo en el siglo veinte subsecuente a los transplantes y a la exterminación de los depredadores. La variación en la abundancia de alces a lo largo de Montana, Idaho y el oriente de Washington estuvo influenciada por la depredación humana, pero también por la historia biogeográfica, las diferencias en hábitat y el cambio climático. [source] Towards a New Logic for Front End Management: From Drug Discovery to Drug Design in Pharmaceutical R&DCREATIVITY AND INNOVATION MANAGEMENT, Issue 2 2007Maria Elmquist Under pressure to innovate and be cost-effective at the same time, R&D departments are being challenged to develop new organizations and processes for Front End activities. This is especially true in the pharmaceutical industry. As drug development becomes more risky and costly, the discovery departments of pharmaceutical companies are increasingly being compelled to provide strong drug candidates for efficient development processes and quick market launches. It is argued that the Fuzzy Front End consists less of the discovery or recognition of opportunities than of the building of expanded concepts: the notion of concept generation is revisited, suggesting the need for a new logic for organizing Front End activities in order to support sustainable innovative product development. Based on an in-depth empirical study at a European pharmaceutical company, this paper contributes to improved understanding of the actual management practices used in the Front End. Using a design reasoning model (the C-K model), it also adds to the growing body of literature on the management of Front End activities in new product development processes. [source] Discovery and recognition of purine receptor subtypes on plateletsDRUG DEVELOPMENT RESEARCH, Issue 1-2 2001Susanna M.O. HouraniArticle first published online: 9 MAY 200 Abstract The effects of purines on platelets have been known since the 1960s, when Born demonstrated aggregation induced by ADP and its inhibition by adenosine and by ATP. The inhibition by adenosine is not specific for ADP, and adenosine acts at a separate receptor to stimulate adenylate cyclase, which has an inhibitory effect on platelet function. Studies using selective agonists and antagonists have shown that the platelet receptor is of the A2A subtype and this has been confirmed using A2A knockout mice. The situation with ADP is more complex, and there has been controversy about the number of ADP receptors on platelets. ADP causes shape change, aggregation, mobilisation of calcium from intracellular stores, rapid calcium influx, and inhibition of adenylate cyclase, and the relationship between these is becoming clearer. Two cloned P2 receptors have been detected on platelets, P2X1 and P2Y1, and a third P2Y receptor is thought to exist. The P2X1 receptor is responsible for the rapid calcium influx and can be activated by ATP as well as by ADP, but is likely to be desensitised under normal experimental conditions and its pathophysiological role is uncertain. The P2Y1 receptor is responsible for calcium mobilisation, shape change, and the initiation of aggregation, and these responses are abolished in P2Y1 knockout mice, while the other P2Y receptor is responsible for inhibition of adenylate cyclase and is required for full aggregation. ATP is a competitive antagonist at both these P2Y receptors, while some nucleotide analogues can discriminate between them. Drug Dev. Res. 52:140,149, 2001. © 2001 Wiley-Liss, Inc. [source] Monoclonal antibody proteomics: Discovery and prevalidation of chronic obstructive pulmonary disease biomarkers in a single stepELECTROPHORESIS, Issue 23 2007Eszter Csanky Abstract We define mAb proteomics as the global generation of disease specific antibodies that permit mass screening of biomarkers. An integrated, high-throughput, disease-specific mAb-based biomarker discovery platform has been developed. The approach readily provided new biomarker leads with the focus on large-scale discovery and production of mAb-based, disease-specific clinical assay candidates. The outcome of the biomarker discovery process was a highly specific and sensitive assay, applicable for testing of clinical validation paradigms, like response to treatment or correlation with other clinical parameters. In contrast to MS-based or systems biology-based strategies, our process produced prevalidated clinical assays as the outcome of the discovery process. By re-engineering the biomarker discovery paradigm, the encouraging results presented in this paper clearly demonstrate the efficiency of the mAb proteomics approach, and set the grounds for the next steps of studies, namely, the hunt for candidate biomarkers that respond to drug treatment. [source] Discovery of the genus Skidmorella Johnson (Coleoptera: Ptiliidae) in Japan, with descriptions of two new speciesENTOMOLOGICAL SCIENCE, Issue 4 2003Yoshihiro SAWADA Abstract The genus Skidmorella Johnson, previously known only from the South Pacific islands, is discovered in Japan. The type species, Skidmorella magnifica Johnson, is confirmed from Japan as the first record of the species other than the type locality. In addition, two new species, Skidmorella amamiana sp. nov. and Skidmorella quadrisulucia sp. nov., are described from the Ryukyus, Japan. Phylogenetic relationships of the genus Skidmorella and its allies are discussed on the basis of their morphological characters. [source] The Impact of Environment and Entrepreneurial Perceptions on Venture-Creation Efforts: Bridging the Discovery and Creation Views of EntrepreneurshipENTREPRENEURSHIP THEORY AND PRACTICE, Issue 5 2010Linda Edelman Recent literature has highlighted two conflicting theories of entrepreneurship. In the "discovery" perspective, objective environmental conditions are considered to be the source of entrepreneurial opportunities and thus drivers of subsequent entrepreneurial action. The "creation" view, in contrast, is based on entrepreneurial perceptions and socio-cognitive enactment processes. While empirical studies have separately utilized each of these perspectives, few attempts have been made to integrate insights from both theories to empirically examine the interrelationships among environmental conditions, entrepreneurial perceptions, entrepreneurial action, and outcomes. In this article, we explicate the roles that both objective environmental conditions and entrepreneurial perceptions of opportunity and resource availability play in the process of firm creation. Utilizing longitudinal data on nascent entrepreneurs, we find that as hypothesized, entrepreneurs' opportunity perceptions mediate between objective characteristics of the environment and the entrepreneurs' efforts to start a new venture. Contrary to our expectations, we do not find a similar mediating effect for perceived resource availability. These findings have important implications for further theory development in entrepreneurship as well as for practice and education in the field. [source] Use of Chronic Epilepsy Models in Antiepileptic Drug Discovery: The Effect of Topiramate on Spontaneous Motor Seizures in Rats with Kainate-induced EpilepsyEPILEPSIA, Issue 1 2005Heidi L. Grabenstatter Summary:,Purpose: Potential antiepileptic drugs (AEDs) are typically screened on acute seizures in normal animals, such as those induced in the maximal electroshock and pentylenetet-razole models. As a proof-of-principle test, the present experiments used spontaneous epileptic seizures in kainate-treated rats to examine the efficacy of topiramate (TPM) with a repeated-measures, crossover protocol. Methods: Kainic acid was administered in repeated low doses (5 mg/kg) every hour until each Sprague,Dawley rat experienced convulsive status epilepticus for >3 h. Six 1-month trials (n = 6,10 rats) assessed the effects of 0.3,100 mg/kg TPM on spontaneous seizures. Each trial involved six pairs of TPM and saline-control treatments administered as intraperitoneal injections on alternate days with a recovery day between each treatment day. Data analysis included a log transformation to compensate for the asymmetric distribution of values and the heterogeneous variances, which appeared to arise from clustering of seizures. Results: A significant effect of TPM was observed for 12 h (i.e., two 6-h periods) after a 30-mg/kg injection, and full recovery from the drug effect was complete within 43 h. TPM exerted a significant effect at doses of 10, 30, and 100 mg/kg, and the effects of TPM (0.3,100 mg/kg) were dose dependent. Conclusions: These data suggest that animal models with spontaneous seizures, such as kainate- and pilocarpine-treated rats, can be used efficiently for rapid testing of AEDs with a repeated-measures, crossover protocol. Furthermore, the results indicate that this design allows both dose,effect and time-course-of-recovery studies. [source] Therapy Discovery for Pharmacoresistant Epilepsy and for Disease-modifying Therapeutics: Summary of the NIH/NINDS/AES Models II WorkshopEPILEPSIA, Issue 12 2003James P. Stables First page of article [source] Macrocyclization of Di-Boc-guanidino-alkylamines Related to Guazatine Components: Discovery and Synthesis of Innovative Macrocyclic AmidinoureasEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 3 2009Daniele Castagnolo Abstract The synthesis of new and innovative macrocyclic amidinoureas from linear di-Boc-guanidino-alkylamines related to guazatine was accomplished. The macrocyclization reaction proceeds under mild conditions affording 11- to 16-membered rings with a new and previously undescribed structure in good yields. Enantiomerically pure macrocyclic amidinoureas were also synthesised. The strict correlation between macrocyclic amidinoureas and the natural productguazatine makes them very actractive also from a biological point of view. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009) [source] Escherichia coli mediated urinary tract infections: Are there distinct uropathogenic E. coli (UPEC) pathotypes?FEMS MICROBIOLOGY LETTERS, Issue 2 2005Carl F. Marrs Abstract A variety of virulence genes are associated with Escherichia coli mediated urinary tract infections. Particular sets of virulence factors shared by bacterial strains directing them through a particular pathogenesis process are called a "pathotype." Comparison of co-occurrence of potential urinary tract infection (UTI) virulence genes among different E. coli isolates from fecal and UTI collections provides evidence for multiple pathotypes of uropathogenic E. coli, but current understanding of critical genetic differences defining the pathotypes is limited. Discovery of additional E. coli genes involved in uropathogenesis and determination of their distribution and co-occurrences will further define UPEC pathotypes and allow for a more detailed analysis of how these pathotypes might differ in how they cause disease. [source] Discovery of New Green Phosphors and Minimization of Experimental Inconsistency Using a Multi-Objective Genetic Algorithm-Assisted Combinatorial MethodADVANCED FUNCTIONAL MATERIALS, Issue 11 2009Asish Kumar Sharma Abstract A multi-objective genetic algorithm-assisted combinatorial materials search (MOGACMS) strategy was employed to develop a new green phosphor for use in a cold cathode fluorescent lamp (CCFL) for a back light unit (BLU) in liquid crystal display (LCD) applications. MOGACMS is a method for the systematic control of experimental inconsistency, which is one of the most troublesome and difficult problems in high-throughput combinatorial experiments. Experimental inconsistency is a very serious problem faced by all scientists in the field of combinatorial materials science. For this study, experimental inconsistency and material property were selected as dual objective functions that were simultaneously optimized. Specifically, in an attempt to search for promising phosphors with high reproducibility, luminance was maximized and experimental inconsistency was minimized using the MOGACMS strategy. A divalent manganese-doped alkali alkaline germanium oxide system was screened using MOGACMS. As a result of MOGA reiteration, we identified a phosphor, Na2MgGeO4:Mn2+, with improved luminance and reliable reproducibility. [source] Discovery of the causeway and the mortuary temple of the Pyramid of Amenemhat II using near-surface magnetic investigation, Dahshour, Giza, EgyptGEOPHYSICAL PROSPECTING, Issue 2 2010T. Abdallatif ABSTRACT The main outbuildings of the Amenemhat II pyramid complex in Dahsour were yet to be discovered due to a very long subjection of the area to the military authorities and also the demolition of the pyramid itself. We describe the discovery of some of these outbuildings using near-surface magnetic investigations. A gradiometer survey was conducted in the area east of the pyramid to measure the vertical magnetic gradient with a high resolution instrument at 0.5 m sampling interval. The data showed some undesirable field effects such as grid discontinuities, grid slope, traverse stripe effects, spikes and high frequencies originating from recent ferrous contamination. These undesirable effects were addressed to produce an enhanced display. We have successfully detected four main structures in the area east of the pyramid; the causeway that connected the mortuary temple with the valley temple during the Middle Kingdom of the 12th Dynasty, the mortuary temple and its associated rooms, ruins of an ancient working area and an Egyptian-style tomb structure called a Mastaba. An improved recognition for these structures was accomplished by using the analytic signal and Euler deconvolution techniques. Excavation of a small part within the study area has proven the reliability of magnetic discoveries and the shallowness and composition of the detected features. [source] | |||||||||||||||||||||||||||||||||||||