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Kinds of Insights Terms modified by Insights Selected AbstractsNEW INSIGHT INTO THE SIGNALLING PATHWAYS OF HEAT STRESS-INDUCED MYOCARDIAL PRECONDITIONING: PROTEIN KINASE C, TRANSLOCATION AND HEAT SHOCK PROTEIN 27 PHOSPHORYLATIONCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 3 2004Claire Arnaud SUMMARY 1.,Heat stress (HS) is known to induce delayed preconditioning against myocardial infarction 24 h later, but the exact signalling pathway of this response remains to be elucidated. In previous studies, we have shown evidence for the implication of protein kinase C (PKC) and p38 mitogen-activated protein kinase (MAPK) in the HS-induced reduction in infarct size. Furthermore, in their phosphorylated state, small heat shock proteins (Hsp27) seem to confer cytoskeletal protection. In the present study, we sought to determine the effect of HS on the subcellular distribution of PKC isoforms and on Hsp27 phosphorylation. 2.,Rats were subjected to either HS (42°C for 15 min; HS group) or sham anaesthesia (sham group) before their hearts were excised. Myocardial tissue extracts obtained 20 min or 24 h after HS were processed for western blot analysis. 3.,In the HS group, PKC, translocated from the cytosolic to the particulate fraction (4426 ± 128 vs 6258 ± 316 arbitrary units; P = 0.002). Chelerythrine (5 mg/kg, i.p.), a PKC inhibitor, abolished this translocation. Western blot analysis of Hsp27 24 h after HS showed a marked increase in protein expression and phosphorylation in the particulate fraction. 4.,In the present study, we have shown that HS induces the translocation of PKC, from the cytosolic to the particulate fraction. Along with our previous observation that PKC is a trigger of HS-induced myocardial preconditioning, the results of the present study suggest an important role of the , isoform of PKC in this cardioprotective mechanism. Furthermore, we have also demonstrated that the cytoprotective protein Hsp27 is phosphorylated following HS. Therefore, we can conclude that PKC and MAPK/Hsp27 are involved in the signalling pathway of HS-induced cardioprotection. [source] ETHICS AND THE MARKET ECONOMY: INSIGHTS FROM CATHOLIC MORAL THEOLOGYECONOMIC AFFAIRS, Issue 2 2004Samuel Gregg The ethical dimension of market solutions to problems is often neglected by their proponents. This article examines the market from the standpoint of orthodox Roman Catholic moral theology. It illustrates how Catholic theologians have contributed to thinking about the market, draws attention to Catholicism's positive assessment of entrepreneurship, and outlines paths for future Catholic reflection on the market. [source] ASYMMETRY IN STRUCTURAL DEFENSES: INSIGHTS INTO SELECTIVE PREDATION IN THE WILDEVOLUTION, Issue 9 2003C. A. Bergstrom Abstract Assessment of geographical patterns in fluctuating asymmetry (small, random differences between sides of bilateral characters) among populations shows promise as a tool to resolve the relative biomechanical importance of traits, in addition to being a possible indicator of habitat quality. We used 115 endemic freshwater populations of threespine stickleback (Gasterosteus aculeatus) from Haida Gwaii (Queen Charlotte Islands), British Columbia, Canada, to explore the degree of concordance between geographical variation of asymmetry in a predator defense structure (bony lateral plates) and geographical variation in several indirect measures of predation regime as well as several abiotic habitat variables. We found a geographical cline in the population frequency of lateral plate asymmetries, with reduced asymmetry in the southern clear-water regions of the archipelago characterized by long reaction distances and greater chance of capture by predators, and elevated asymmetry in the northern stained-water regions with poor visibility and low chances of capture. Lateral plate asymmetry was strongly correlated with expression of several defensive armor traits, including total plate numbers among populations, mean cross-sectional diameter of stickleback with the dorsal and pelvic spines erect, and mean degree of overlap between the plates and spine supports. There were no significant correlations between frequency of asymmetric fish and any of our abiotic habitat variables. Stickleback with structural plate asymmetries had fewer trout-induced scars than symmetric fish in the significant majority of populations, and there was a decrease in structural plate asymmetry with age in stained-water habitats, suggesting that trout predators may be selectively removing asymmetric fish in some lakes. This study provides evidence that geographical variation in developmental stability of threespine stickleback, as seen in the frequencies of asymmetry, reflects differences among populations in the importance of structural defenses to fitness rather than differences in habitat quality, and that asymmetry may be a target of selection by predators in wild populations. [source] TIME TO THE MOST RECENT COMMON ANCESTOR AND DIVERGENCE TIMES OF POPULATIONS OF COMMON CHAFFINCHES (FRINGILLA COELEBS) IN EUROPE AND NORTH AFRICA: INSIGHTS INTO PLEISTOCENE REFUGIA AND CURRENT LEVELS OF MIGRATIONEVOLUTION, Issue 1 2002Cortland K. Griswold Abstract We analyzed sequences from a 275-bp hypervariable region in the 5, end of the mitochondrial DNA control region in 190 common chaffinches (Fringilla coelebs) from 19 populations in Europe and North Africa, including new samples from Greece and Morocco. Coalescent techniques were applied to estimate the time to the most recent common ancestor (TMRCA) and divergence times of these populations. The first objective of this study was to infer the locations of refugia where chaffinches survived the last glacial episode, and this was achieved by estimating the TMRCA of populations in regions surrounding the Mediterranean that were unglaciated in the late Pleistocene. Although extant populations in Iberia, Corsica, Greece, and North Africa harbor haplotypes that are basal in a phylogenetic tree, this information alone cannot be used to infer that these localities served as refugia, because it is impossible to infer the ages of populations and their divergence times without also considering the population genetic processes of mutation, migration, and drift. Provided we assume the TMRCAs of populations are a reasonable estimate of a population's age, coalescent-based methods place resident populations in Iberia, Corsica, Greece, and North Africa during the time of the last glacial maximum, suggesting these regions served as refugia for the common chaffinch. The second objective was to determine when populations began diverging from each other and to use this as a baseline to estimate current levels of gene flow. Divergence time estimates suggest that European populations began diverging about 60,000 years before present. The relatively recent divergence of populations in North Africa, Italy, and Iberia may explain why classic migration estimates based on equilibrium assumptions are high for these populations. We compare these estimates with nonequilibrium-based estimates and show that the nonequilibrium estimates are consistently lower than the equilibrium estimates. [source] METHODOLOGICAL INSIGHTS: Using seismic sensors to detect elephants and other large mammals: a potential census techniqueJOURNAL OF APPLIED ECOLOGY, Issue 3 2005JASON D. WOOD Summary 1Large mammal populations are difficult to census and monitor in remote areas. In particular, elephant populations in Central Africa are difficult to census due to dense forest, making aerial surveys impractical. Conservation management would be improved by a census technique that was accurate and precise, did not require large efforts in the field, and could record numbers of animals over a period of time. 2We report a new detection technique that relies on sensing the footfalls of large mammals. A single geophone was used to record the footfalls of elephants and other large mammal species at a waterhole in Etosha National Park, Namibia. 3Temporal patterning of footfalls is evident for some species, but this pattern is lost when there is more than one individual present. 4We were able to discriminate between species using the spectral content of their footfalls with an 82% accuracy rate. 5An estimate of the energy created by passing elephants (the area under the amplitude envelope) can be used to estimate the number of elephants passing the geophone. Our best regression line explained 55% of the variance in the data. This could be improved upon by using an array of geophones. 6Synthesis and applications. This technique, when calibrated to specific sites, could be used to census elephants and other large terrestrial species that are difficult to count. It could also be used to monitor the temporal use of restricted resources, such as remote waterholes, by large terrestrial species. [source] ELUCIDATION OF IMAGES IN THE BOOK OF CHANGES: ANCIENT INSIGHTS INTO MODERN LANGUAGE PHILOSOPHY AND HERMENEUTICSJOURNAL OF CHINESE PHILOSOPHY, Issue 4 2004MING DONG GUArticle first published online: 15 NOV 200 [source] THE HYDROCARBON POTENTIAL OF LEBANON: NEW INSIGHTS FROM REGIONAL CORRELATIONS AND STUDIES OF JURASSIC DOLOMITIZATIONJOURNAL OF PETROLEUM GEOLOGY, Issue 3 2004F. H. Nader This paper presents an updated review of the petroleum prospects of Lebanon. We briefly describe the known hydrocarbon shows in Lebanon and compare them with adjacent countries, leading to the construction of a model for hydrocarbon migration which takes into account regional facies and reservoir correlations. The oldest exposed rocks in Lebanon are the Jurassic carbonates of the Kesrouane Formation (over 1,000m thick). This formation can be divided into a basal unit dominated by seepage-reflux stratabound dolostones (the Chouane Member,) and an overlying limestone-prone unit (the Nahr Ibrahim Member). A two-stage dolomitisation model for the Jurassic carbonates in Lebanon has recently been proposed by the authors. According to this model, second-stage Late Jurassic hydrothermal dolomitisation is believed to have occurred as a result of the circulation of mixed dolomitising fluids along faults. Hence, the resulting dolostones are fault-controlled and strata-discordant, and may occur at any level within the Kesrouane Formation, locally redolomitising the Chouane Member dolostones and replacing the Nahr Ibrahim Member limestones. In this paper, we discuss the implications of diagenesis (especially dolomitisation) on the petroleum prospects of the Kesrouane Formation in Lebanon. The hydrothermal fault-related dolostones possess porosities of up to 20%, which result from intercrystalline and mouldic porosity enhancement. Porosities in the stratabound reflux dolostones (Early Jurassic) and limestones are much lower. The fact that most of the Jurassic system in onshore Lebanon was affected by meteoric diagenesis during the Late Jurassic - Early Cretaceous and the Cenozoic may downgrade hydrocarbon prospectivity. However, offshore areas far from the meteoric realm may have been less (or not at all) affected by meteoric invasion. If effective seals are present there, these areas may host promising Jurassic reservoir units. We also review the prospectivity of unexposed Triassic potential reservoir units in onshore Lebanon (e. g. the "Qartaba" structure). By analogy with the Syrian portion of the Palmyride Basin, Triassic strata here may include both reservoir units and evaporite seals. [source] EMILIANIA HUXLEYI (HAPTOPHYTA) HOLDS PROMISING INSIGHTS FOR PHOTOSYNTHESISJOURNAL OF PHYCOLOGY, Issue 3 2000S. W. Jeffrey First page of article [source] ON THE ROAD TO PARADIS: NEW INSIGHTS FROM AMS DATES AND STABLE ISOTOPES AT LE DÉHUS, GUERNSEY, AND THE CHANNEL ISLANDS MIDDLE NEOLITHICOXFORD JOURNAL OF ARCHAEOLOGY, Issue 2 2010RICK J. SCHULTING Summary We here report the results of a programme of AMS dating and stable isotope analysis on human remains from the chambered tomb of Le Déhus, Guernsey. An early use-phase in the range 4100,3900 BC is indicated, confirming the monument's attribution to the Middle Neolithic II as defined in western France. Late Neolithic burial activity is also identified. Stable carbon isotope measurements provide little or no evidence for the consumption of marine foods, although stable nitrogen isotope values are unusually high. These results are situated in the wider context of Neolithic mortuary monuments of the Channel Islands and Normandy. [source] THE DOUET ALIGNMENT ON THE ISLAND OF HOEDIC (MORBIHAN, FRANCE): NEW INSIGHTS INTO STANDING STONE ALIGNMENTS IN BRITTANYOXFORD JOURNAL OF ARCHAEOLOGY, Issue 3 2009JEAN-MARC LARGE Summary The island of Hoedic in southern Brittany has numerous archaeological remains of later prehistoric date. It became famous through the discovery in the 1930s of a Mesolithic cemetery, but the island also has abundant archaeological evidence from the earliest Neolithic period onwards. These include several megalithic monuments, the most significant being alignments of standing stones. One of these alignments has recently been excavated, and investigation of another is in progress. The discoveries resulting from this work provide new insights into the origin of the phenomenon, its chronological and cultural context and the techniques that were used to create these structures. Above all, it offers a new approach to considering the meaning of these alignments. [source] SHA,AR HAGOLAN AND NEW INSIGHTS ON NEAR EASTERN PROTO-HISTORIC URBAN CONCEPTSOXFORD JOURNAL OF ARCHAEOLOGY, Issue 2 2009DAVID BEN-SHLOMO Summary. The new results from the Pottery Neolithic site of Sha,ar Hagolan in Israel, dated to 6400,6000 BC (calibrated), reveal advanced notions of settlement planning, including the introduction of courtyard houses, a street system and infrastructure such as the construction of a water well. It is suggested, on the basis of the Near Eastern archaeological evidence from the eighth to sixth millennia BC, that early signs of urban concepts may be found at this stage. These signs show the development of ,functionally hierarchical' concepts reflected in domestic architecture and settlement planning. At least from the cognitive point of view, these concepts may be on the direct trajectory towards the full-blown urban centres of the fourth and third millennia BC in the Near East. [source] BILLENGSELLIDE AND ORTHIDE BRACHIOPODS: NEW INSIGHTS INTO EARLIEST ORDOVICIAN EVOLUTION AND BIOGEOGRAPHY FROM NORTHERN IRANPALAEONTOLOGY, Issue 1 2009LEONID E. POPOV Abstract:, The eastern Alborz Mountains of Iran comprise a significant peri-Gondwanan terrane relevant to the early evolution of late Cambrian , early Ordovician brachiopods incorporated into the emerging benthic biota of the Paleozoic Evolutionary Fauna. A low diversity brachiopod assemblage from the late Tremadocian unit of the Lashkarak Formation contains six new species including the polytoechioideans Polytoechia and Protambonites and the orthoideans Paralenorthis, Ranorthis, Tarfaya and Xianorthis. The fauna preserves the earliest records of Polytoechia, unknown previously outside Laurentia and the Uralian margin of Baltica, and of Paralenorthis and Ranorthis, which were widespread along Gondwanan margins and in Baltica from the Floian (Arenig), plus Xianorthis, known hitherto only from the Floian of South China. The enigmatic Tarfaya has an impunctate shell fabric and setigerous perforations along the posterior margin, indicating placement within the Orthoidea in a new Family Tarfayidae. New species of Polytoechia, Protambonites, Paralenorthis, Ranorthis, Tarfaya, Xianorthis are described. [source] INSIGHTS INTO SERVICE OPERATIONS MANAGEMENT: A RESEARCH AGENDAPRODUCTION AND OPERATIONS MANAGEMENT, Issue 2 2003ALEDA V. ROTH This paper offers insights regarding an agenda for service operations management (SOM) research. First, we motivate the need for an SOM research agenda. Second, we offer a research framework that paints a broad-based picture of key architectural elements in the SOM research landscape. The framework builds upon prior and emerging research for designing, delivering and evaluating services. Third, in order to stimulate future research in SOM, we use this framework to hone in on five understudied and emerging research themes that underpin our proposed SOM research agenda. [source] INSIGHTS INTO NORTH MESOPOTAMIAN ,METALLIC WARE'*ARCHAEOMETRY, Issue 2 2006T. BROEKMANS With the aim of shedding new light on the still poorly understood North Mesopotamian metallic ware, ceramic and soil samples from Tell Beydar (northeastern Syria, third millennium bc) were investigated using a range of analytical techniques, including optical microscopy, SR,XRD and SEM,EDX. The objective of this work was to differentiate calcareous metallic ware from non-calcareous ware without the aid of chemical analyses and to find further validation of the existing hypothesis that the former group is an imitation of the latter. A third group of metallic wares from Tell Beydar is believed to be of non-local, still regional origin. [source] ANOMALIES, PROBINGS, INSIGHTS: KEN FOREMAN'S ROLE IN THE SAMPLING INFERENCE CONTROVERSY OF THE LATE 20TH CENTURYAUSTRALIAN & NEW ZEALAND JOURNAL OF STATISTICS, Issue 4 2005Ken Brewer Summary This paper is based on the author's recollections of work done for and with E.K. Foreman, and later developments of that work. It describes most particularly the author's early intimations of the potential for using prediction models in survey sampling, the reasons why the use of such models, especially for inferential purposes, was so strongly resisted in the second half of the 20th century, the manner in which randomization and prediction inferences can be combined, and some advantages flowing from that combination. [source] SBIRT Outcomes in Houston: Final Report on InSight, a Hospital District-Based Program for Patients at Risk for Alcohol or Drug Use ProblemsALCOHOLISM, Issue 8 2009The InSight Project Research Group Background:, Screening, Brief Intervention, and Referral to Treatment (SBIRT) services have been implemented as the standard of care for patients in the Harris County Hospital District (HCHD). The present analysis addresses alcohol and drug use for patients admitted over a 39-month period from July 1, 2005 through September 30, 2008. Methods:, Patients were screened for alcohol and drug use at medical admission. Those who were positive received further assessment and were transitioned to receive services as appropriate. A sample of consenting patients who were positive and received services was contacted at 6 months for a follow-up interview. Using an intent-to-treat (ITT) protocol, the analysis included all patients who were assigned for follow-up, including those with completed follow-ups as well as those who could not be contacted at follow-up. Patients not contacted at follow-up were assumed to have maintained their baseline drug and alcohol consumption levels. Results:, Of 59,760 patients who were screened by generalists (primarily nurses, physicians, and medical care technicians), 15,241 (26%) were positive and received further assessment and services. The 6-month follow-up interview completion rate was 66%. The ITT sample consisted of all 1,937 patients who were assigned for follow-up. There was an overall reduction in the number of patients reporting any days of heavy drinking from 70% at intake to 37% at 6-month follow-up and a reduction in the mean number of days of heavy drinking from 7.8 days at intake to 4.1 days at follow-up. The number of patients reporting any days of drug use was 82% at intake versus 33% at follow-up, and the mean number of days of drug use declined from 8.3 days at intake to 4.2 days at follow-up. Conclusions:, The results were consistent with but of greater magnitude than most other studies reporting positive outcomes for SBIRT patients. Drug use and heavy alcohol use were found to decrease substantially from admission to follow-up. This finding holds good for all levels of drug or alcohol misuse severity, with the highest severity patients showing the largest decreases. Future studies are needed to control for potential regression to the mean effects and to develop improved understanding of differences in outcomes by race/ethnicity. [source] Significance of Modeling Error in Structural Parameter EstimationCOMPUTER-AIDED CIVIL AND INFRASTRUCTURE ENGINEERING, Issue 1 2001Masoud Sanayei Structural health monitoring systems rely on algorithms to detect potential changes in structural parameters that may be indicative of damage. Parameter-estimation algorithms seek to identify changes in structural parameters by adjusting parameters of an a priori finite-element model of a structure to reconcile its response with a set of measured test data. Modeling error, represented as uncertainty in the parameters of a finite-element model of the structure, curtail capability of parameter estimation to capture the physical behavior of the structure. The performance of four error functions, two stiffness-based and two flexibility-based, is compared in the presence of modeling error in terms of the propagation rate of the modeling error and the quality of the final parameter estimates. Three different types of parameters are used in the parameter estimation procedure: (1) unknown parameters that are to be estimated, (2) known parameters assumed to be accurate, and (3) uncertain parameters that manifest the modeling error and are assumed known and not to be estimated. The significance of modeling error is investigated with respect to excitation and measurement type and locations, the type of error function, location of the uncertain parameter, and the selection of unknown parameters to be estimated. It is illustrated in two examples that the stiffness-based error functions perform significantly better than the corresponding flexibility-based error functions in the presence of modeling error. Additionally, the topology of the structure, excitation and measurement type and locations, and location of the uncertain parameters with respect to the unknown parameters can have a significant impact on the quality of the parameter estimates. Insight into the significance of modeling error and its potential impact on the resulting parameter estimates is presented through analytical and numerical examples using static and modal data. [source] Mathematical skills in Williams syndrome: Insight into the importance of underlying representationsDEVELOPMENTAL DISABILITIES RESEARCH REVIEW, Issue 1 2009Kirsten O'Hearn Abstract Williams syndrome (WS) is a developmental disorder characterized by relatively spared verbal skills and severe visuospatial deficits. Serious impairments in mathematics have also been reported. This article reviews the evidence on mathematical ability in WS, focusing on the integrity and developmental path of two fundamental representations, namely those that support judgments of "how much" (i.e., magnitude) and "how many" (i.e., number of objects). Studies on magnitude or "number line" representation in WS suggest that this core aspect of mathematical ability, is atypical in WS throughout development, causing differences on some but not all aspects of math. Studies on the representation of small numbers of objects in WS are also reviewed, given the proposed links between this type of representation and early number skills such as counting. In WS, representation appears to be relatively typical in infancy but limitations become evident by maturity, suggesting a truncated developmental trajectory. The math deficits in WS are consistent with neurological data indicating decreased gray matter and hypoactivation in parietal areas in WS, as these areas are implicated in mathematical processing as well as visuospatial abilities and visual attention. In spite of their deficits in core mathematical representations, people with WS can learn many mathematical skills and show some strengths, such as reading numbers. Thus individuals with WS may be able to take advantage of their relatively strong verbal skills when learning some mathematical tasks. The uneven mathematical abilities found in persons with WS provide insight into not only appropriate remediation for this developmental disorder but also into the precursors of mathematical ability, their neural substrates, and their developmental importance. © 2009 Wiley-Liss, Inc. Dev Disabil Res Rev 2009;15:11,20. [source] Insight in early psychosis: a 1 year follow-upACTA PSYCHIATRICA SCANDINAVICA, Issue 2002A. Mintz Insight is an important prognostic indicator in early psychosis, as its presence can enhance treatment compliance, thus reducing the risk of clinical deterioration. The Calgary Early Psychosis Programme (EPP) is a comprehensive treatment programme for individuals experiencing their first episode of psychosis. Purpose, (i) to examine insight on admission and determine if change occurred in the first year of treatment and (ii) to determine if insight was associated with other symptoms. Methods, Participants were 180 consecutive admissions to EPP who completed a 1-year follow-up. Insight, positive and negative symptoms were measured with the PANSS. Depression was measured with the Calgary Depression Scale. Results, There was a significant improvement in insight from initial to 1-year follow-up (P < 0.001). Insight was positively correlated with positive and negative symptoms (P < 0.001) over time. Insight was negatively correlated with depression (P < 0.001) at the initial assessment. Conclusions, In these first episode patients, there is a significant improvement in insight over time. Insight is significantly related to positive and negative symptoms and to depression in the initial stages of the illness when the presence of depression is notable. [source] Bench,shelf system dynamic characteristics and their effects on equipment and contentsEARTHQUAKE ENGINEERING AND STRUCTURAL DYNAMICS, Issue 13 2006Tara C. Hutchinson Abstract Economic losses during past earthquakes are strongly associated with damage and failure to nonstructural equipment and contents. Among the vast types of nonstructural elements, one important category, is scientific equipment in biological or chemical laboratories. These equipment are often mounted on heavy ceramic bench-tops of bench,shelf systems, which in turn may amplify the dynamic motions imposed. To investigate the seismic response of these types of systems, a series of shake table and field experiments were conducted considering different representative bench and shelf-mounted equipment and contents. Results from shake table experiments indicate that these equipment are generally sliding-dominated. In addition, the bench,shelf system is observed to be very stiff and when lightly loaded, has a fundamental frequency between 10 and 16 Hz. An approximate 50% reduction in the first and second fundamental frequencies is observed considering practical loading conditions. Insight into a broader range of system response is provided by conducting eigenvalue and time history analyses. Non-linear regression through the numerical data indicate acceleration amplification ratios , range from 2.6 to 1.4 and from 4.3 to 1.6, for fixed,fixed and pinned,pinned conditions, respectively. Both the experimental and numerical results support the importance of determining the potential dynamic amplification of motion in the context of accurately determining the maximum sliding displacement of support equipment and contents. Copyright © 2006 John Wiley & Sons, Ltd. [source] Horizontal canal benign paroxysmal positioning vertigo with ipsilateral hearing lossEUROPEAN JOURNAL OF NEUROLOGY, Issue 1 2004H. Rambold The etiology of benign paroxysmal positioning vertigo (h-BPPV) of the horizontal semicircular is unknown. Insight was obtained from two patients with h-BPPV and associated hearing impairment. Based on the different inner ear lesion patterns in neurolabyrinthitis contrary to ischemic labyrinthine infarction we assessed multiple vestibulo-cochlear functions for the first time in two patients who suffered from h-BPPV with sudden unilateral hearing loss. While in patient no. 1 the lesion pattern (posterior canal paresis in addition to the sudden hearing loss) could possibly be caused by ischemia of the common cochlear artery, the lesion pattern of patient no. 2 (hearing loss and ipsilateral paresis of the posterior and horizontal semicircular canal) exceeds the typical vascular labyrinthine territories and may indicate viral neurolabyrinthitis. [source] An Efficient Synthesis of Substituted meta -Halophenols and Their Methyl Ethers: Insight into the Reaction MechanismEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 15 2010Faiz Ahmed Khan Abstract An expeditious synthetic methodology leading to substituted meta -halophenols and their corresponding methyl ether derivatives through acid-mediated fragmentation of suitably substituted dihalonorbornyl ketones has been devised. The reaction sequence consists of TBTH-mediated (TBTH is tri- n -butyltin hydride) selective bridgehead halogen reduction of easily accessible Diels,Alder adducts derived from 1,2,3,4-tetrahalo-5,5-dimethoxycyclopentadiene and ,-substituted vinyl acetates, with subsequent conversion into the requisite bicyclic ketones by a two-step hydrolysis/oxidation approach. An extensive mechanistic investigation based on isotope labeling and cross experiments has been carried out and plausible mechanistic pathways based on these results have been proposed. The absence of halogen atoms at the bridgehead positions steers the reaction through a novel pathway involving the incorporation of proton (or deuterium) followed by elimination of HX (or DX), so the described methodology also provides a reliable route to ortho-para dideuteratedphenolic derivatives. [source] A Theoretical Insight into the Mechanism of the Silver-Catalysed Transsiliranation ReactionEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 7 2010José Antonio Mayoral Abstract DFT calculations on a silver-catalysed transsiliranation reaction (silylene transfer from a silirane to an alkene) have shown the key role of a silylenesilver ion in the catalyticcycle. Although the corresponding triflate-bound species has previously been detected by NMR and IR spectroscopy, no significant silylene-transfer activity is predicted for such a nonionised structure. Several experimental results can be explained by this new reaction mechanism. [source] Enantioselective Michael Addition of Aromatic Ketones to Nitroolefins Catalyzed by Bifunctional Thioureas and Mechanistic InsightEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 4 2010Bai-Lin Li Abstract A highly enantioselective Michael reaction of aromatic ketones with nitroolefins was accomplished in the presence of a chiral bifunctional primary amine,thiourea catalyst and 4-nitrobenzoic acid as the co-catalyst; the corresponding adducts were obtained in excellent enantioselectivities (up to 99,%,ee) and yields (up to 98,%). The catalytic mechanism of the Michael reaction was confirmed through the ESI-MS detection of proposed reaction intermediates and the 1H NMR detection of hydrogen bonding between thiourea and the nitroolefins. DFT calculations showed that chiral moieties of the thiourea impacted the yields and enantioselectivities of the adducts remarkably, which corresponds to the observed experimental results. [source] Insight into the molecular mechanisms of glucocorticoid receptor action promotes identification of novel ligands with an improved therapeutic indexEXPERIMENTAL DERMATOLOGY, Issue 8 2006Heike Schäcke Abstract:, Glucocorticoids are highly effective in the therapy of inflammatory and autoimmune disorders. Their beneficial action is restricted because of their adverse effects upon prolonged usage. Topical glucocorticoids that act locally have been developed to significantly reduce systemic side effects. Nonetheless, undesirable cutaneous effects such as skin atrophy persist from the use of topical glucocorticoids. There is therefore a high medical need for drugs as effective as glucocorticoids but with a reduced side-effect profile. Glucocorticoids function by binding to and activating the glucocorticoid receptor that positively or negatively regulates the expression of specific genes. Several experiments suggest that the negative regulation of gene expression by the glucocorticoid receptor accounts for its anti-inflammatory action. This occurs through direct or indirect binding of the receptor to transcription factors such as activator protein-1, nuclear factor- ,B or interferon regulatory factor-3 that are already bound to their regulatory sites. The positive action of the receptor occurs through homodimer binding of the receptor to discrete nucleotide sequences and this possibly contributes to some of the adverse effects of the hormone. Glucocorticoid receptor ligands that promote the negative regulatory action of the receptor with reduced positive regulatory function should therefore show improved therapeutic potential. A complete separation of the positive from the negative regulatory activities of the receptor has so far not been possible because of the interdependent nature of the two regulatory processes. Nevertheless, considerable improvement in the therapeutic action of glucocorticoid receptor ligands is being achieved through the use of key molecular targets for screening novel glucocorticoid receptor ligands. [source] Insight into Proton Conduction of Immobilised Imidazole Systems Via Simulations and Impedance Spectroscopy,FUEL CELLS, Issue 3-4 2008W. L. Cavalcanti Abstract The proton conduction in immobilised imidazole systems has been investigated in order to support the design of new membrane materials for polymer electrolyte membrane fuel cells (PEMFC). In the experimental part of this work, proton conductivities are measured via impedance spectroscopy. The simulation and modelling are performed combining molecular dynamics simulations and energy barrier calculations; the analysis is done via the proton jump energy barrier, collision ratio and radial distribution function. The dependence of the proton mobility on the temperature, spacer length and the density of conducting groups per area is presented. Donors and acceptors groups approach to each other within a distance from 2.8 to 3,Å where the energy barrier for a proton transfer is very low, which favours the proton jump under the studied conditions. The proton conductivity increases with increase in the spacer length. The simulation results are in good agreement with the proton conductivities presented. [source] The evolution of gnathostome development: Insight from chondrichthyan embryologyGENESIS: THE JOURNAL OF GENETICS AND DEVELOPMENT, Issue 12 2009J. Andrew Gillis Alcian blue skeletal preparations of wild-type (front) and retinoic acid-treated (back) embryos of the little skate, Leucoraja erinacea. As in paired fins, the cartilaginous gill rays of L. erinacea are patterned by a retinoic acid-regulated Sonic hedghog (Shh)-Fibroblast growth factor 8 (Fgf8) feedback loop, and exposure to exogenous retinoic acid induces ectopic Shh expression and mirror-image gill ray duplications. (Cover design by Kalliopi Monoyios and Randy Dahn). See the review by Gillis and Shubin in this issue. [source] The Energy of Charge-Transfer States in Electron Donor,Acceptor Blends: Insight into the Energy Losses in Organic Solar CellsADVANCED FUNCTIONAL MATERIALS, Issue 12 2009Dirk Veldman Abstract Here, a general experimental method to determine the energy ECT of intermolecular charge-transfer (CT) states in electron donor,acceptor (D,A) blends from ground state absorption and electrochemical measurements is proposed. This CT energy is calibrated against the photon energy of maximum CT luminescence from selected D,A blends to correct for a constant Coulombic term. It is shown that ECT correlates linearly with the open-circuit voltage (Voc) of photovoltaic devices in D,A blends via eVoc,=,ECT,,,0.5,eV. Using the CT energy, it is found that photoinduced electron transfer (PET) from the lowest singlet excited state (S1 with energy Eg) in the blend to the CT state (S1,,,CT) occurs when Eg,,,ECT,>,0.1,eV. Additionally, it is shown that subsequent charge recombination from the CT state to the lowest triplet excited state (ET) of D or A (CT,,,T1) can occur when ECT,,,ET,>,0.1,eV. From these relations, it is concluded that in D,A blends optimized for photovoltaic action: i) the maximum attainable Voc is ultimately set by the optical band gap (eVoc,=,Eg,,,0.6,eV) and ii) the singlet,triplet energy gap should be ,EST,<,0.2,eV to prevent recombination to the triplet state. These favorable conditions have not yet been met in conjugated materials and set the stage for further developments in this area. [source] Autoantibodies to coagulation factorsHAEMOPHILIA, Issue 102 2010J.-M. R. SAINT-REMY Summary., Tolerance to autoantigens such as coagulation factors is the result of censoring mechanisms occurring at the level of the thymus and bone marrow for autoreactive T and B cells, respectively. In addition, peripheral mechanisms, both intrinsic and extrinsic further control activation of autoreactive cells that have escaped central deletion. Emergence of autoimmunity can occur from disturbances of these control mechanisms by a number of events, many of which are incompletely understood. Insight into this clinically important field is expected from exploitation of recent animal models. [source] Insight into molecular changes of the FIX protein in a series of Italian patients with haemophilia BHAEMOPHILIA, Issue 3 2006M. P. BICOCCHI Summary., Deficiency or dysfunction of factor IX FIX leads to haemophilia B (HB), an X-linked, recessive, bleeding disorder. On a molecular basis, HB is due to a heterogeneous spectrum of mutations spread throughout the F9 gene. In several instances, a cause-effect relation has been elucidated, in others predicted possibilities have been offered by crystallography inspection and by software-constructed models of the protein. The aim of this study was to contribute to the understanding of HB molecular pathology. The F9 missense mutations we identified in 21 unrelated Italian HB patients by direct sequencing of the whole F9 coding regions were inspected for the causative effect they provoked on the ensuing transcript, and on the protein structure. Each alteration was studied in order to: (i) characterize the defect on the basis of the nature of the mutation; (ii) identify the predicted defect that is induced in the gene and (iii) speculate about the potential, detrimental effects which upset the protein functionality through an idealized FIX model. The resulting data may further contribute to the comprehension of the mechanisms underlying the disease. [source] | |||||||||||||||||||||||||||||||||||||