Well-known

Distribution by Scientific Domains

Terms modified by Well-known

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  • well-known cause
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  • well-known effects
  • well-known example
  • well-known fact
  • well-known feature
  • well-known inducer
  • well-known inhibitor
  • well-known limitation
  • well-known mechanism
  • well-known methods
  • well-known phenomenon
  • well-known problem
  • well-known procedure
  • well-known result
  • well-known risk factor

  • Selected Abstracts


    Study of a highly accurate and fast protein,ligand docking method based on molecular dynamics

    CONCURRENCY AND COMPUTATION: PRACTICE & EXPERIENCE, Issue 14 2005
    M. Taufer
    Abstract Few methods use molecular dynamics simulations in concert with atomically detailed force fields to perform protein,ligand docking calculations because they are considered too time demanding, despite their accuracy. In this paper we present a docking algorithm based on molecular dynamics which has a highly flexible computational granularity. We compare the accuracy and the time required with well-known, commonly used docking methods such as AutoDock, DOCK, FlexX, ICM, and GOLD. We show that our algorithm is accurate, fast and, because of its flexibility, applicable even to loosely coupled distributed systems such as desktop Grids for docking. Copyright © 2005 John Wiley & Sons, Ltd. [source]


    Influence of dentin on pH of 2% chlorhexidine gel and calcium hydroxide alone or in combination

    DENTAL TRAUMATOLOGY, Issue 3 2010
    Laila Gonzales Freire
    Most of the times, these objectives are not achieved solely by chemomechanical preparation, and intracanal dressing may be necessary. In these cases, calcium hydroxide is used as a root canal dressing due to its well-known and recognized antimicrobial activity. Chlorhexidine has a wide spectrum of antimicrobial activity and its association with calcium hydroxide has been recommended in an attempt to amplify antimicrobial effects of calcium hydroxide. It is also known that dentin exerts a buffering effect under wide pH variations, and may be responsible for decreasing the antimicrobial activity of drugs inside the root canal. The objectives of this study were to assess the pH of 2% chlorhexidine gel and calcium hydroxide alone or in combination, as well as the influence of dentin on the pH of these compounds. Dentin powder was obtained from bovine teeth and added as 1.8% to the volume of the medications. All substances were individually stored in plastic flasks, in triplicate. A pH meter was used at five different moments to assess pH in viscous medium: immediately after preparation and after 24 h, and 7, 14, and 21 days. Results were analyzed by paired Student's t -test. Statistically significant differences were observed in the 2% chlorhexidine gel group alone or associated with calcium hydroxide and added of dentin powder (P < 0.05). Mean pH values indicated the influence of dentin powder because of a significant increase in pH. Calcium hydroxide with propylene glycol as the vehicle always showed high pH, demonstrating that this compound was not affected by the presence of dentin. [source]


    Integration of diverse inputs in the regulation of Caenorhabditis elegans DAF-16/FOXO

    DEVELOPMENTAL DYNAMICS, Issue 5 2010
    Jessica N. Landis
    Abstract In a remarkably conserved insulin signaling pathway that is well-known for its regulation of longevity in worms, flies, and mammals, the major C. elegans effector of this pathway, DAF-16/FOXO, also modulates many other physiological processes. This raises the question of how DAF-16/FOXO chooses the correct targets to achieve the appropriate response in a particular context. Here, we review current knowledge of tissue-specificity and interacting partners that modulate DAF-16/FOXO functional output. Developmental Dynamics 239:1405,1412, 2010. © 2010 Wiley-Liss, Inc. [source]


    Comparative evaluation of human embryonic stem cell lines derived from zygotes with normal and abnormal pronuclei

    DEVELOPMENTAL DYNAMICS, Issue 2 2010
    Qing Huan
    Abstract Human embryonic stem (hES) cell lines have been derived from normally or abnormally fertilized zygotes. However, the similar and different properties of these two types of hES cell lines are not well-known. To address this question, we generated nine hES cell lines from zygotes containing normal (2PN) and abnormal (0PN, 1PN, 3PN) pronuclei. A side-by-side comparison showed that all cell lines exhibited distinct identity and karyotypical stability. They expressed similar "stemness" markers and alkaline phosphatase activity and differentiated into three embryonic germ lineages in embryoid bodies and teratomas. Under neural differentiation-promoting conditions, they were directed into neural progenitors and neurons. However, a variation in cell cycle and the relative abundance of gene expression of undifferentiated and differentiated markers were observed. These variations were also seen among individually derived normal hES cell lines. Thus, normal hES cell lines can be developed from fertilized zygotes with abnormal pronuclei usually excluded from clinical use. Developmental Dynamics 239:425,438, 2010. © 2009 Wiley-Liss, Inc. [source]


    Organizational effects of maternal testosterone on reproductive behavior of adult house sparrows

    DEVELOPMENTAL NEUROBIOLOGY, Issue 14 2008
    Jesko Partecke
    Abstract Despite the well-known, long-term, organizational actions of sex steroids on phenotypic differences between the sexes, studies of maternal steroids in the vertebrate egg have mainly focused on effects seen in early life. Long-term organizational effects of yolk hormones on adult behavior and the underlying mechanisms that generate them have been largely ignored. Using an experiment in which hand-reared house sparrows (Passer domesticus) from testosterone- or control-treated eggs were kept under identical conditions, we show that testosterone treatment in the egg increased the frequency of aggressive, dominance, and sexual behavior of 1-year-old, reproductively competent house sparrows. We also show that circulating plasma levels of progesterone, testosterone, 5,-dihydrotestosterone, and 17,-estradiol did not differ between treatment groups. Thus, a simple change in adult gonadal hormone secretion is not the primary physiological cause of long-term effects of maternal steroids on adult behavior. Rather, differences in adult behavior caused by exposure to yolk testosterone during embryonic development are likely generated by organizational modifications of brain function. Furthermore, our data provide evidence that hormone-mediated maternal effects are an epigenetic mechanism causing intra-sexual variation in adult behavioral phenotype. © 2008 Wiley Periodicals, Inc. Develop Neurobiol 2008 [source]


    Consistent dynamics suggests tight regulation of biophysical parameters in a small network of bursting neurons

    DEVELOPMENTAL NEUROBIOLOGY, Issue 14 2006
    Attila Szücs
    Abstract The neuronal firing patterns in the pyloric network of crustaceans are remarkably consistent among animals. Although this characteristic of the pyloric network is well-known, the biophysical mechanisms underlying the regulation of the systems output are receiving renewed attention. Computer simulations of the pyloric network recently demonstrated that consistent motor output can be achieved from neurons with disparate biophysical parameters among animals. Here we address this hypothesis by pharmacologically manipulating the pyloric network and analyzing the emerging voltage oscillations and firing patterns. Our results show that the pyloric network of the lobster stomatogastric ganglion maintains consistent and regular firing patterns even when entire populations of specific voltage-gated channels and synaptic receptors are blocked. The variations of temporal parameters used to characterize the burst patterns of the neurons as well as their intraburst spike dynamics do not display statistically significant increase after blocking the transient K-currents (with 4-aminopyridine), the glutamatergic inhibitory synapses (with picrotoxin), or the cholinergic synapses (with atropine) in pyloric networks from different animals. These data suggest that in this very compact circuit, the biophysical parameters are cell-specific and tightly regulated. © 2006 Wiley Periodicals, Inc. J Neurobiol, 2006 [source]


    Ethnic differences in plantar pressures in diabetic patients with peripheral neuropathy

    DIABETIC MEDICINE, Issue 4 2008
    M. P. Solano
    Abstract Aims To compare plantar foot pressures between Caucasian and Hispanic diabetic patients with peripheral neuropathy (PN) without a history of foot ulceration and between Caucasian and Hispanic non-diabetic individuals. Methods Forty-four Hispanic diabetic patients with PN (HDPN), 35 Caucasian diabetic patients with PN (CDPN), 41 non-diabetic Hispanic subjects and 33 non-diabetic Caucasian subjects participated. Total and regional peak plantar pressures (PPs) and pressure time integrals (PTIs) were assessed using the EMED-SF-4 plantar pressure system. Results Hispanic diabetic patients with PN had significantly lower peak PP than Caucasian diabetic patients with PN in the entire foot (552.4 ± 227.9 vs. 810.1 ± 274.6 kPa; P < 0.001), forefoot (464.1 ± 222.6 vs. 699.6 ± 323.1 kPa; P < 0.001), hindfoot (296.3.4 + 101.8 vs. 398.1 + 178.3 kPa; P < 0.01) and at the fifth metatarsal head (MTH5; 204.3 ± 143.2 vs. 388.2 ± 273.9 kPa; P < 0.001). The PTI in the entire foot, forefoot and MTH5 were also lower in HDPN than in CDPN. The ethnic differences between the diabetic groups with PN for the entire foot, forefoot and MTH5 remained significant after adjusting for the effect of age, gender, weight and duration of diabetes. There were no significant differences in peak PP and PTI among non-diabetic individuals, except for a lower peak PP at the MTH5 in Hispanic compared with Caucasian subjects. Conclusions Despite a well-known higher incidence of foot complications in diabetic Hispanic subjects, dynamic plantar pressures are lower in Hispanic diabetic patients with PN when compared with their Caucasian counterparts, suggesting that differences in other risk factors exist between these two ethnic groups. [source]


    Morphologic predictors of papillary carcinoma on fine-needle aspiration of thyroid with ThinPrep® preparations

    DIAGNOSTIC CYTOPATHOLOGY, Issue 6 2001
    Yilin Zhang M.D.
    Abstract Although the cytologic features of papillary carcinoma of the thyroid are well-known, none is entirely specific. We conducted this study to determine the minimal criteria necessary to achieve 100% specificity for the diagnosis of papillary carcinoma on fine-needle aspiration (FNA). Forty patients with histologically confirmed papillary carcinoma and 17 patients with other thyroid lesions who underwent preoperative FNA at Beth Israel Deaconess Medical Center during a 4-yr period were included in the study. All cytology slides were prepared with the ThinPrep® processing technique. Various architectural and nuclear features were evaluated, with a score assigned to each feature, and correlated with the histologic diagnosis of papillary carcinoma. Intranuclear inclusions, papillary and/or sheet arrangements, nuclear grooves, powdery chromatin, nuclear molding, high cellularity, and small nucleoli were significantly associated with papillary carcinoma (P < 0.05). The requirement of any intranuclear inclusions and many nuclear grooves, or a minimum of sum of scores (of the above eight features) of 10, yields 100% specificity and approximately 70% sensitivity. Cases with fewer features can be reported as suspicious or indeterminate for papillary carcinoma. A quantitative/probabilistic approach in the reporting of thyroid FNA provides a practical guide for management of patients with thyroid nodules. Diagn. Cytopathol. 24:378,383, 2001. © 2001 Wiley-Liss, Inc. [source]


    Conceptual Equivocation and Epistemic Relevance

    DIALECTICA, Issue 2 2009
    Mikkel Gerken
    Much debate has surrounded "switching" scenarios in which a subject's reasoning is said to exhibit the fallacy of equivocation (Burge 1988; Boghossian 1992, 1994). Peter Ludlow has argued that such scenarios are "epistemically prevalent" and, therefore, epistemically relevant alternatives (Ludlow 1995a). Since a distinctive feature of the cases in question is that the subject blamelessly engages in conceptual equivocation, we may label them ,equivocational switching cases'. Ludlow's influential argument occurs in a discussion about compatibilism with regards to anti-individualism (or content externalism) and self-knowledge. However, the issue has wide-reaching consequences for many areas of epistemology. Arguably, the claim that equivocational switching cases are epistemically relevant may bear on the epistemology of inference, testimony, memory, group rationality and belief revision. Ludlow's argument proceeds from a now well-known "down to Earth" switching-case of a subject, Biff, who travels between the US and the UK. I argue that Ludlow's case-based argument fails to support the general claim that conceptual equivocational switching cases are prevalent and epistemically relevant. Thus, the discussion addresses the basis of some poorly understood issues regarding the epistemological consequences of anti-individualism. Simultaneously, the discussion is broadened from the narrow focus on self-knowledge. Finally, the critical discussion serves as the basis for some general reflections on epistemic relevance and the epistemic risks associated with conceptual equivocation. Specifically, I suggest that philosophy is an area where the risk of conceptual equivocation is extraordinarily high. [source]


    Why are ferns regularly over-represented on state and provincial rare plant lists?

    DIVERSITY AND DISTRIBUTIONS, Issue 6 2006
    Matthew Wild
    ABSTRACT Several recent studies have suggested that rare species are not randomly distributed throughout plant taxa. This would appear to apply to North American ferns, which are frequently over-represented on local lists of rare plant species. However, such lists often paint a skewed portrait of the true situation because of our tendency to recognize the rarity of well-known and charismatic species while ignoring that of lesser-known or less-appreciated species. In order to verify if this over-representation of ferns is a real and consistent trend throughout local floras in North America, we used data from what we consider to be the most complete and objective available database: NatureServe Explorer (http://www.natureserve.org/explorer/). We compiled data on total vascular plant species, total fern species, as well as rare vascular plant species and rare fern species for each North American subnational (Canadian province or US state) flora. Rare species were defined as those belonging to one of NatureServe's ,at risk' categories. The null hypothesis that the contribution of rare ferns to total rare species did not differ from their contribution to the total vascular flora was assessed using ,2. Out of 64 subnational floras, we obtained significantly higher values than expected in 28 cases, and significantly lower in only one case. Similar trends hold true for individual fern families. These tendencies could be related to several factors of anthropogenic, biological, climatological, evolutionary, and geographical origin. However, we believe that the main reason is related to scale, namely the geopolitical units at which rarity is often studied. Our results illustrate one of the problems of a parochial approach to conservation, where the perceived rarity of an entire taxon is exaggerated because of the scale at which rarity is addressed. [source]


    Association between tobacco control policies and smoking behaviour among adolescents in 29 European countries

    ADDICTION, Issue 11 2009
    Anne Hublet
    ABSTRACT Aims To investigate the associations between well-known, cost-effective tobacco control policies at country level and smoking prevalence among 15-year-old adolescents. Design Multi-level modelling based on the 2005,06 Health Behaviour in School-aged Children Study, a cross-national study at individual level, and with country-level variables from the Tobacco Control Scale and published country-level databases. Setting Twenty-nine European countries. Participants A total of 25 599 boys and 26 509 girls. Main outcome measures Self-reported regular smoking defined as at least weekly smoking, including daily smoking (dichotomous). Findings Interaction effects between gender and smoking policies were identified, therefore boys and girls were analysed separately. Large cross-national differences in smoking prevalence were documented. Intraclass correlations (ICC) of 0.038 (boys) and 0.035 (girls) were found. In the final multi-level model for boys, besides the significance of the individual variables such as family affluence, country-level affluence and the legality of vending machines were related significantly to regular smoking [b(country affluence) = ,0.010; b(partial restriction vending machines) = ,0.366, P < 0.05]. Price policy was of borderline significance [b(price policy) = ,0.026, P = 0.050]. All relationships were in the expected direction. The model fit is not as good for girls; only the legality of vending machines had a borderline significance in the final model [b(total ban vending machines) = ,0.372, P = 0.06]. Conclusions For boys, some of the currently recommended tobacco control policies may help to reduce smoking prevalence. However, the model is less suitable for girls, indicating gender differences in the potential efficacy of smoking policies. Future research should address this issue. [source]


    Frameshift mutations induced by four isomeric nitroacridines and their des-nitro counterpart in the lacZ reversion assay in Escherichia coli

    ENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Issue 2 2006
    George R. Hoffmann
    Abstract Acridines are well-known as compounds that intercalate noncovalently between DNA base pairs and induce ±1 frameshift mutations at sites of monotonous repeats of a single base. Reactive derivatives of acridines, including acridine mustards and nitroacridines, form covalent adducts in DNA and exhibit mutagenic properties different from the simple intercalators. We compared the frameshift mutagenicity of the cancer chemotherapy drug nitracrine (1-nitro-9-(3,-dimethylaminopropylamino)-acridine), its des-nitro counterpart 9-(3,-dimethylaminopropylamino)-acridine (DAPA), and its 2-, 3-, and 4-nitro isomers (2-, 3-, and 4-nitro-DAPA) in the lacZ reversion assay in Escherichia coli. DAPA is a simple intercalator, much like the widely studied 9-aminoacridine. It most strongly induced ±1 frameshift mutations in runs of guanine residues and more weakly induced ,1 frameshifts in a run of adenine residues. A nitro group in the 1, 3, or 4 position of DAPA reduced the yield of ±1 frameshift mutations. DAPA weakly induced ,2 frameshifts in an alternating CG sequence. In contrast, nitracrine and its 3-nitro isomer resembled the 3-nitroacridine Entozon in effectively inducing ,2 frameshift mutations. The 2- and 4-nitro isomers were less effective than the 1- and 3-nitro compounds in ,2 frameshift mutagenesis. The results are interpreted with respect to intercalation, steric interactions, effects of base strength on DNA binding, enzymatic processing, and a slipped mispairing model of frameshift mutagenesis. Environ. Mol. Mutagen., 2006. © 2005 Wiley-Liss, Inc. [source]


    Minerals as Model Compounds for Cu/ZnO Catalyst Precursors: Structural and Thermal Properties and IR Spectra of Mineral and Synthetic (Zincian) Malachite, Rosasite and Aurichalcite and a Catalyst Precursor Mixture

    EUROPEAN JOURNAL OF INORGANIC CHEMISTRY, Issue 10 2009
    Malte Behrens
    Abstract The Cu/ZnO system is a model for Cu/ZnO/Al2O3 catalysts, which are employed industrially for the synthesis of methanol. These catalysts are usually prepared from mixed basic carbonate precursors. A complex phase mixture, with constituents structurally related to the minerals rosasite andaurichalcite, is present at the industrially applied composition (Cu/Zn , 70:30). Using minerals and phase-pure synthetic samples as references, a comprehensive characterisation of such a phase mixture, including the determination of the individual compositions of the different phases, has been attempted by complementary analytical laboratory techniques (XRD, TGA, IR). The results are critically discussed in light of the complexity of the system. A thermally very stable carbonate species , well-known for mixed synthetic systems , is also detected for the mineral reference samples. Significant amounts of amorphous phases are found to be present in the synthetic zincian malachite sample but not in synthetic aurichalcite or the catalyst precursor. A simplified explanation for the shift of the characteristic 20 reflection of the malachite structure as a function of Zn incorporation based on the varying average Jahn,Teller distortion of the MO6 octahedra is proposed. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009) [source]


    Rapid functional plasticity in the primary somatomotor cortex and perceptual changes after nerve block

    EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 12 2004
    Thomas Weiss
    Abstract The mature human primary somatosensory cortex displays a striking plastic capacity to reorganize itself in response to changes in sensory input. Following the elimination of afferent return, produced by either amputation, deafferentation by dorsal rhizotomy, or nerve block, there is a well-known but little-understood ,invasion' of the deafferented region of the brain by the cortical representation zones of still-intact portions of the brain adjacent to it. We report here that within an hour of abolishing sensation from the radial and medial three-quarters of the hand by pharmacological blockade of the radial and median nerves, magnetic source imaging showed that the cortical representation of the little finger and the skin beneath the lower lip, whose intact cortical representation zones are adjacent to the deafferented region, had moved closer together, presumably because of their expansion across the deafferented area. A paired-pulse transcranial magnetic stimulation procedure revealed a motor cortex disinhibition for two muscles supplied by the unaffected ulnar nerve. In addition, two notable perceptual changes were observed: increased two-point discrimination ability near the lip and mislocalization of touch of the intact ulnar portion of the fourth finger to the neighbouring third finger whose nerve supply was blocked. We suggest that disinhibition within the somatosensory system as a functional correlate for the known enlargement of cortical representation zones might account for not only the ,invasion' phenomenon, but also for the observed behavioural correlates of the nerve block. [source]


    EVOLUTION OF POECILOGONY AND THE BIOGEOGRAPHY OF NORTH AMERICAN POPULATIONS OF THE POLYCHAETE STREBLOSPIO

    EVOLUTION, Issue 4 2000
    Stefan R. Schulze
    Abstract. Invertebrate interspecific developmental patterns can be highly variable and, taxonomically, are considered only weakly constrained. Intraspecifically, some invertebrate species possess multiple developmental modes,a condition known as poecilogony. Closer examination of most putative poecilogenous species, however, has not supported poecilogony, but rather has uncovered hidden or cryptic species. The polychaete Streblospio benedicti is a well-known, poecilogenous species found along the coast of North America. We collected mitochondrial cytochrome subunit I DNA sequence data from 88 individuals taken from 11 locations along the Atlantic, Gulf, and Pacific Coasts of the United States to provide a phylogenetic framework from which to interpret intraspecific variation in larval life history and brooding structure morphology in this species. Our results are consistent with a recent revision of the species into two separate species: S. benedicti, a pouched brooding form distributed along the Atlantic and Pacific Coasts, and S. gynobranchiata, a branchiate brooding form in the Gulf of Mexico. Contrary to the redescription, S. benedicti is paraphyletic because the pouched brooding population in Vero Beach, Florida shows strong genetic affinity with Gulf of Mexico populations (S. gynobranchiata). However, S. benedicti is a true poecilogenous species, with both lecithotrophic and planktotrophic individuals possessing identical mitochondrial DNA haplotypes. Crossbreeding experiments further support the molecular phylogeny with reproductive isolation demonstrated between, but not within, the major phylogenetic clades consistent with the previously described species. The genetic break near Vero Beach, Florida, corresponds to a well-known phylogeographic boundary, but the estimated time of separation for the Streblospio spp., approximately 10 million years before present, predates all other known phylogeographic subdivisions in this area. This suggests that biogeographic sundering in this region is a recurrent event. Divergence times within the major Streblospio spp. clades are recent and indicate that changes in larval life history as well as brooding structure morphology are highly plastic and can evolve rapidly. [source]


    Breath-holding and its breakpoint

    EXPERIMENTAL PHYSIOLOGY, Issue 1 2006
    M. J. Parkes
    This article reviews the basic properties of breath-holding in humans and the possible causes of the breath at breakpoint. The simplest objective measure of breath-holding is its duration, but even this is highly variable. Breath-holding is a voluntary act, but normal subjects appear unable to breath-hold to unconsciousness. A powerful involuntary mechanism normally overrides voluntary breath-holding and causes the breath that defines the breakpoint. The occurrence of the breakpoint breath does not appear to be caused solely by a mechanism involving lung or chest shrinkage, partial pressures of blood gases or the carotid arterial chemoreceptors. This is despite the well-known properties of breath-hold duration being prolonged by large lung inflations, hyperoxia and hypocapnia and being shortened by the converse manoeuvres and by increased metabolic rate. Breath-holding has, however, two much less well-known but important properties. First, the central respiratory rhythm appears to continue throughout breath-holding. Humans cannot therefore stop their central respiratory rhythm voluntarily. Instead, they merely suppress expression of their central respiratory rhythm and voluntarily ,hold' the chest at a chosen volume, possibly assisted by some tonic diaphragm activity. Second, breath-hold duration is prolonged by bilateral paralysis of the phrenic or vagus nerves. Possibly the contribution to the breakpoint from stimulation of diaphragm muscle chemoreceptors is greater than has previously been considered. At present there is no simple explanation for the breakpoint that encompasses all these properties. [source]


    Kinetic mechanism for p38 MAP kinase ,

    FEBS JOURNAL, Issue 18 2005
    A partial rapid-equilibrium random-order ternary-complex mechanism for the phosphorylation of a protein substrate
    p38 Mitogen-activated protein kinase alpha (p38 MAPK,) is a member of the MAPK family. It is activated by cellular stresses and has a number of cellular substrates whose coordinated regulation mediates inflammatory responses. In addition, it is a useful anti-inflammatory drug target that has a high specificity for Ser-Pro or Thr-Pro motifs in proteins and contains a number of transcription factors as well as protein kinases in its catalog of known substrates. Fundamental to signal transduction research is the understanding of the kinetic mechanisms of protein kinases and other protein modifying enzymes. To achieve this end, because peptides often make only a subset of the full range of interactions made by proteins, protein substrates must be utilized to fully elucidate kinetic mechanisms. We show using an untagged highly active form of p38 MAPK,, expressed and purified from Escherichia coli[Szafranska AE, Luo X & Dalby KN (2005) Anal Biochem336, 1,10) that at pH 7.5, 10 mm Mg2+ and 27 °C p38 MAPK, phosphorylates ATF2,115 through a partial rapid-equilibrium random-order ternary-complex mechanism. This mechanism is supported by a combination of steady-state substrate and inhibition kinetics, as well as microcalorimetry and published structural studies. The steady-state kinetic experiments suggest that magnesium adenosine triphosphate (MgATP), adenylyl (,,,-methylene) diphosphonic acid (MgAMP-PCP) and magnesium adenosine diphosphate (MgADP) bind p38 MAPK, with dissociation constants of KA = 360 µm, KI = 240 µm, and KI > 2000 µm, respectively. Calorimetry experiments suggest that MgAMP-PCP and MgADP bind the p38 MAPK,,ATF2,115 binary complex slightly more tightly than they do the free enzyme, with a dissociation constant of Kd , 70 µm. Interestingly, MgAMP-PCP exhibits a mixed inhibition pattern with respect to ATF2,115, whereas MgADP exhibits an uncompetitive-like pattern. This discrepancy occurs because MgADP, unlike MgAMP-PCP, binds the free enzyme weakly. Intriguingly, no inhibition by 2 mm adenine or 2 mm MgAMP was detected, suggesting that the presence of a ,-phosphate is essential for significant binding of an ATP analog to the enzyme. Surprisingly, we found that inhibition by the well-known p38 MAPK, inhibitor SB 203580 does not follow classical linear inhibition kinetics at concentrations >,100 nm, as previously suggested, demonstrating that caution must be used when interpreting kinetic experiments using this inhibitor. [source]


    Dangers relating to fires in carbon-fibre based composite material

    FIRE AND MATERIALS, Issue 4 2005
    Tommy Hertzberg
    Abstract Inhalable carbon fibres have been suspected to pose similar threats to human health as asbestos fibres. It is well-known that fibres having a diameter of less than 3 µm might be inhaled and transported deep into the human respiratory system. Some composite materials use carbon fibres as structural reinforcement. These fibres do not pose any risks as such as they are firmly connected to the laminate and surrounded by a polymer matrix. Also, these fibres typically have diameters >6 µm and thus, are not inhalable. However, if the material is exposed to a fire, the carbon material might be oxidized and fractionated and thereby, inhalable fibres might be generated into the fire smoke. The capability of carbon fibre-based composite material to produce dangerous inhalable fibres from different combustion scenarios has been investigated. It was found that the risk of fires generating inhalable carbon fibres is related to the surface temperature, the oxygen level and the airflow field close to the material surface. The temperatures necessary for oxidation of the carbon fibre is so high that it is possible that only a flashover situation will pose any real danger. Other possible danger scenarios are highly intense fires (e.g. a liquid fuel fire), or situations where structural damage is part of the fire scenario. Copyright © 2005 John Wiley & Sons, Ltd. [source]


    Larval lobster (Homarus americanus) distribution and drift in the vicinity of the Gulf of Maine offshore banks and their probable origins

    FISHERIES OCEANOGRAPHY, Issue 2 2005
    G. C. HARDING
    Abstract Surveys for lobster larvae in offshore waters of the north-eastern Gulf of Maine in 1983, 1987 and 1989 confirm that local hatching occurs mainly at depths <100 m over the banks, including Georges and Browns Banks. Detailed studies in the vicinity of Georges Bank in late July of both 1987 and 1989 indicate that the first and second moult stages were located primarily over the bank whereas stages III and IV lobster were collected both over and off the bank. At times stage IV lobster were more abundant off the bank than over it. The condition of stage III and IV lobster, as measured by a lipid index, was better off than over Georges Bank in 1988 and 1989 indicating a possible physiological advantage to being off the bank. In addition, the higher surface temperatures off Georges Bank would shorten larval development time to settlement. To determine the probable hatch sites of stage IV lobster collected off of Browns Bank in 1983 and off of Georges in 1987 and 1989, a 3-D circulation model of the Gulf of Maine was used to simulate larval lobster drift backwards in time. In all cases, areas off Cape Cod, MA, and off Penobscot Bay, ME were suggested as the source of the larvae, although most of the larval trajectories never reached these near-shore waters that are well-known, larval hatching areas. The model-projected larval release times match most closely the observed inshore hatch off Massachusetts but model uncertainties mean that coastal Maine cannot be ruled out as a source. Georges Bank is also a potential source because the present model does not take into account short-term wind events, off-bank eddy transport or the possibility of directed off-bank larval swimming. Examination of weather records prior to and during our 1988 and 1989 sampling periods indicates that winds were not of sufficient intensity and duration to induce larval transport off Georges Bank. The shedding of eddies from the northern flank of Georges Bank into the Gulf of Maine are a relatively common phenomenon during summer but not enough is known about them to evaluate their contribution to possible cross-bank transport of lobster larvae. Directed larval swimming is another possible source for the stage IV lobster found near Georges Bank. Plankton distributions across the northern frontal zone of Georges Bank in 1988 were used as proxies for the scarce larval lobsters. The more surface distribution of the microplankton, in particular, supports the possibility that wind and eddy events may be important in the transport of stage III and IV lobsters off of Georges Bank. Further studies are needed to evaluate these possible additional sources of advanced stage lobster larvae found off of the offshore banks. [source]


    Estimating unobservable valuation parameters for illiquid assets

    ACCOUNTING & FINANCE, Issue 3 2009
    Glenn Boyle
    G12; R33 Abstract A problem that often arises in applied finance is one where decision-makers need to choose a value for some parameter that will affect the cash flows between two parties involved in the operation of an illiquid asset. Because the values of the cash flows also depend on various unobservable parameters, identifying the value of the policy parameter that achieves the desired allocation between the parties is no simple task, often resulting in disputes and the invocation of ad hoc approaches. We show how this problem can be solved using an extension of the well-known ,implied volatility' technique from option pricing, and apply it to the determination of equilibrium rental rates on ground leases of commercial land. [source]


    Partially Irreversible Investment Decisions and Taxation under Uncertainty: A Real Option Approach

    GERMAN ECONOMIC REVIEW, Issue 2 2002
    Caren Sureth
    The paper applies contingent claims analysis in a real option investment model in order to investigate taxation's influence on investor's decisions under uncertainty. The results show the distortion from realistic-type tax systems, allow to identify a tax-induced paradox in option valuation for specific settings and acknowledge the property of investment neutrality of well-known ,ideal' tax systems in the context of different degrees of irreversibility. Furthermore, it is clarified that the idea of risk-neutral valuation cannot be adopted by the real option approach in general. [source]


    Mandeville's Journey into the Big, Wide World

    GERMAN RESEARCH, Issue 1 2006
    Susanne Röhl Dr.
    Jean de Mandeville and his report of a fantastic journey around the world were once as well-known as Marco Polo. The distribution of the French manuscript versions of this medieval "bestseller" can now be reconstructed [source]


    Coordination as a Political Problem in Coordinated Market Economies

    GOVERNANCE, Issue 1 2006
    KATHLEEN THELEN
    The purpose of this article is to explore the political dynamics of employer coordination in three well-known "coordinated market economies." We examine differences in how employer coordination has been organized in Sweden, Germany, and Japan in the area of industrial relations, and we examine the extent to which such coordination represents a self-sustaining equilibrium, as some of the most influential treatments suggest. To preview the findings, we argue that precisely the intensification of cooperation between labor and management in some firms and industries (that the "varieties of capitalism" literature correctly emphasizes) has paradoxically had deeply destabilizing collateral effects that have undermined or are undermining these systems as they were traditionally constituted. All three cases are characterized not so much by a full-blown breakdown of coordination so much as a very significant reconfiguration of the terms and scope of such coordination. Specifically, all three countries feature the emergence of new or intensified forms of dualism,different in each case based on different starting points,in which continued coordination within a smaller core has in some ways been underwritten through the breaking off of other, more peripheral, firms and workers. [source]


    Semi-presidentialism, Cohabitation and the Collapse of Electoral Democracies, 1990,2008

    GOVERNMENT AND OPPOSITION, Issue 1 2010
    Robert Elgie
    Semi-presidentialism is the situation where a constitution makes provision for both a directly elected fixed-term president and a prime minister and cabinet who are responsible to the legislature. A common argument against the adoption of a semi-presidential constitution by a new democracy is the problem of cohabitation , where a president from one party holds power at the same time as a prime minister from an opposing party and where the president's party is not represented in the cabinet. The concern is that cohabitation creates competing power centres within the executive that are dangerous for young democracies. This article shows that cohabitation has been directly associated with the collapse of a young democracy in only one case. Moreover, by specifying the conditions under which cohabitation can occur, we also show that the threat of cohabitation has been associated with collapse in only one further case. We suggest that this is so because cohabitation refers to a very specific situation that can only occur under a certain combination of circumstances that can often be avoided. Overall, we show that there is little evidence to support one of the most well-known and long-standing arguments against semi-presidentialism. Thus, while semi-presidentialism may indeed be perilous for new democracies, we conclude that it is perilous for reasons other than the problem of cohabitation. [source]


    The Tris(trimethylsilyl)silane/Thiol Reducing System: A Tool for Measuring Rate Constants for Reactions of Carbon-Centered Radicals with Thiols

    HELVETICA CHIMICA ACTA, Issue 10 2006
    Chryssostomos Chatgilialoglu
    Abstract An extension of the well-known ,free-radical-clock' methodology is described that allows one to determine the rate constants of carbon-centered radicals with a variety of thiols by using the tris(trimethylsilyl)silane/thiol couple as a reducing system. A total of 20 rate constants for the hydrogen abstraction from a variety of alkyl-, silyl-, and aryl-substituted thiols by the primary-alkyl radical 2 in toluene at 80° were determined with the aid of the 5- exo-trig cyclization as a timing device. Further, seven rate constants for the hydrogen abstraction from a variety of alkyl- and silyl-substituted thiols by the acyl radical 9 in benzene at 80° were measured using the decarbonylation process as a timing device. The rate constants varied over two orders of magnitude from 106 to 108,M,1 s,1. Substituent effects were rationalized. The radical-trapping abilities of these reducing systems and those of other common hydrogen donors were compared. [source]


    Ab initio Emulsion Polymerization by RAFT (Reversible Addition,Fragmentation Chain Transfer) through the Addition of Cyclodextrins

    HELVETICA CHIMICA ACTA, Issue 8 2006
    Bojana Apostolovic
    Abstract A novel process to produce homo- and copolymers by RAFT polymerization in emulsion is presented. It is known that RAFT-controlled radical polymerization can be conducted in emulsion polymerization without disturbing the radical segregation characteristic of this process, thus leading to polymerization rates identical to those encountered in the corresponding nonliving systems. However, RAFT agents are often characterized by very low water solubility and, therefore, they diffuse very slowly from the monomer droplets, where they are initially solubilized, to the reaction loci, i.e., the polymer particles. Accordingly, when used in emulsion polymerization, they are practically excluded from the reaction. In this work, we show that cyclodextrins, well-known for their ability to form water-soluble complexes with hydrophobic molecules, facilitate the transport across the H2O phase of the RAFT agent to the polymer particles. Accordingly, chains grow through the entire process in a controlled way. This leads to the production of low-polydispersity polymers with well-defined structure and end functionalities as well as to the possibility of synthesizing block copolymers by a radical mechanism. [source]


    Intramitochondrial crystalline inclusions in nonalcoholic steatohepatitis,

    HEPATOLOGY, Issue 6 2009
    Stephen H. Caldwell
    Mitochondrial dysfunction is an important element in the pathogenesis of nonalcoholic steatohepatitis (NASH). Intramitochondrial crystals (IMCs) are a well-documented morphological abnormality seen on transmission electron microscopy in this disease. It has been suggested that IMCs consist of phospholipids, but their exact composition remain uncertain many years after their discovery. Micellar phase transitions of phospholipid bilayers is a well-known but little-studied phenomenon in living systems. Its presence in the mitochondria of NASH would offer significant insight into the disease with possible therapeutic implications. We postulated that intramitochondrial disturbances in NASH are sufficient to produce such transitions and that their detection in fresh biopsies would therefore be a dynamic process. To test this, we performed a blinded, prospective analysis of fresh liver biopsy samples immediately fixed under different conditions. Quantitative transmission electron microscopy morphometry, performed by systematically counting total mitochondria and IMCs within areas of uniform dimension, showed a stepwise decline in IMCs with cooler fixation temperature in each subject studied. Randomization testing (Monte Carlo resampling) confirmed that the detection of IMCs was strongly dependent on fixation temperature (P < 0.0001). Conclusion: These results indicate that the intramitochondrial crystals characteristic of NASH are highly dynamic and unstable structures. The findings offer the strongest support yet for their origin in micellar phase transitions. We speculate that such transitions result from microenvironmental changes within the mitochondria and carry therapeutic implications, especially in regard to dietary manipulations of mitochondrial lipid composition. (HEPATOLOGY 2009.) [source]


    KOSELLECK, ARENDT, AND THE ANTHROPOLOGY OF HISTORICAL EXPERIENCE

    HISTORY AND THEORY, Issue 2 2010
    STEFAN-LUDWIG HOFFMANN
    ABSTRACT This essay is the first attempt to compare Reinhart Koselleck's Historik with Hannah Arendt's political anthropology and her critique of the modern concept of history. Koselleck is well-known for his work on conceptual history as well as for his theory of historical time(s). It is my contention that these different projects are bound together by Koselleck's Historik, that is, his theory of possible histories. This can be shown through an examination of his writings from Critique and Crisis to his final essays on historical anthropology, most of which have not yet been translated into English. Conversely, Arendt's political theory has in recent years been the subject of numerous interpretations that do not take into account her views about history. By comparing the anthropological categories found in Koselleck's Historik with Arendt's political anthropology, I identify similar intellectual lineages in them (Heidegger, Löwith, Schmitt) as well as shared political sentiments, in particular the anti-totalitarian impulse of the postwar era. More importantly, Koselleck's theory of the preconditions of possible histories and Arendt's theory of the preconditions of the political, I argue, transcend these lineages and sentiments by providing essential categories for the analysis of historical experience. [source]


    Supporting long-term workforce planning with a dynamic aging chain model: A case study from the service industry

    HUMAN RESOURCE MANAGEMENT, Issue 5 2010
    Andreas Größler
    Abstract This study demonstrates how a dynamic, aging chain model can support strategic decisions in workforce planning. More specifically, we used a system dynamics model (a modeling and simulation technique originating from supply chain management) to improve the recruiting and training process in a large German service provider in the wider field of logistics. The key findings are that the aging chain of service operators within the company is affected by a variety of delays in, for example, recruiting, training, and promoting employees, and that the structure of the planning process generates cyclic phases of workforce surplus and shortage. The discussion is based on an in-depth case study conducted in the service industry in 2008. Implications are that planning processes must be fine-tuned to account for delays in the aging chain. The dynamic model provides a tool to gain insight into the problem and to improve the actual human resource planning process. The value of the paper lies in the idea of applying a well-known and quantitative method from supply chain management to a human resource management issue. © 2010 Wiley Periodicals, Inc. [source]


    Association of early annual peak influenza activity with El Niño southern oscillation in Japan

    INFLUENZA AND OTHER RESPIRATORY VIRUSES, Issue 4 2008
    Hassan Zaraket
    Background, Seasonality characterizing influenza epidemics suggests susceptibility to climate variation. El Niño southern oscillation (ENSO), which involves two extreme events, El Niño and La Niña, is well-known for its large effects on inter-annual climate variability. The influence of ENSO on several diseases has been described. Objectives, In this study, we attempt to analyze the possible influence of ENSO on the timing of the annual influenza activity peak using influenza-like illness report data in Japan during 1983,2007. Materials, Influenza surveillance data for 25 influenza epidemics, available under the National Epidemiological Surveillance of the Infectious Diseases, was used in this study. ENSO data were obtained from the Japan Meteorological Agency. Results, Influenza-like illness peak week varied largely during the study period, ranging between 4th and 11th weeks (middle of winter to early spring). The average of peak week during ENSO cycles (n = 11, average = 4·5 ± 0·9) was significantly earlier than in non-ENSO years (n = 14, average = 7·6 ± 2·9; P = 0·01), but there was no significant difference in the peak timing between hot (El Niño) and cold (La Niña) phases. Earlier peaks of influenza activity were observed in 16, out of 25, epidemics. These coincided with 10 (90·9%) out of 11 ENSO and 6 (85·7%) out of seven large-scale epidemics. Conclusion, Influenza activity peak occurred earlier in years associated with ENSO and/or large scale epidemics. [source]