Key Role (key + role)

Distribution by Scientific Domains
Distribution within Medical Sciences

Kinds of Key Role

  • play key role

  • Selected Abstracts

    Mitochondrial Oxidative Stress Plays a Key Role in Aging and Apoptosis

    IUBMB LIFE, Issue 5 2000
    Juan Sastre
    Abstract Harman first suggested in 1972 that mitochondria might be the biological clock in aging, noting that the rate of oxygen consumption should determine the rate of accumulation of mitochondrial damage produced by free radical reactions. Later in 1980 Miquel and coworkers proposed the mitochondrial theory of cell aging. Mitochondria from postmitotic cells use O2 at a high rate, hence releasing oxygen radicals that exceed the cellular antioxidant defences. The key role of mitochondria in cell aging has been outlined by the degeneration induced in cells microinjected with mitochondria isolated from fibroblasts of old rats, especially by the inverse relationship reported between the rate of mitochondrial production of hydroperoxide and the maximum life span of species. An important change in mitochondrial lipid composition is the age-related decrease found in cardiolipin content. The concurrent enhancement of lipid peroxidation and oxidative modification of proteins in mitochondria further increases mutations and oxidative damage to mitochondrial DNA (mtDNA) in the aging process. The respiratory enzymes containing the defective mtDNA-encoded protein subunits may increase the production of reactive oxygen species, which in turn would aggravate the oxidative damage to mitochondria. Moreover, superoxide radicals produced during mitochondrial respiration react with nitric oxide inside mitochondria to yield damaging peroxynitrite. Treatment with certain antioxidants, such as sulphur-containing antioxidants, vitamins C and E, or the Ginkgo biloba extract EGb 761, protects against the ageassociated oxidative damage to mtDNA and the oxidation of mitochondrial glutathione. Moreover, the EGb 761 extract also prevents changes in mitochondrial morphology and function associated with aging of the brain and liver. [source]

    Induction of Innate Immune Gene Expression Cascades in Brain Slice Cultures by Ethanol: Key Role of NF-,B and Proinflammatory Cytokines

    ALCOHOLISM, Issue 5 2010
    Jian Zou
    Background:, Postmortem human alcoholic brain has increased expression of proinflammatory cytokines (He and Crews, 2007). Nuclear factor ,B (NF-,B) is a transcription factor known to induce proinflammatory cytokine expression. Ethanol exposure increases NF-,B,DNA binding in rat brain (Crews et al., 2006) and in brain slice cultures in vitro (Zou and Crews, 2006). Using hippocampal-entorhinal cortex (HEC) brain slice cultures, we explored the effect of ethanol on NF-,B,DNA binding, proinflammatory gene expression, and sensitivity to glutamate neurotoxicity. Methods:, The HEC brain slice cultures are prepared from rats on P7 and used after 2 weeks in culture. NF-,B,DNA binding is determined by EMSA, NF-,B subunit,DNA binding by ELISA and mRNA by RT-PCR. Multiple antibody immunohistochemistry and confocal microscopy are used to characterize cell types expressing ethanol-induced genes. Results:, Ethanol treatment results in a progressive increase in NF-,B,DNA binding that includes large increases in NF-,B subunit p50 protein,DNA binding. The expression of NF-,B proinflammatory target genes progressively increased with time of ethanol treatment. Ethanol induces proinflammatory cytokines TNF,, MCP-1, and IL-1,, proinflammatory proteases TACE, and tissue plasminogen activator (tPA) as well as inducible nitric oxide synthase. Blockade of NF-,B by using NF-,B p65 siRNA and BHT reduces ethanol induction of proinflammatory genes. Neutralizing antibody to proinflammatory cytokine TNF, reduces ethanol induction of proinflammatory genes, suggesting cytokine propagation of proinflammatory gene induction. Furthermore, neutralizing antibodies to proinflammatory cytokines and protease tPA inhibitors blunt ethanol sensitization to glutamate neurotoxicity. Conclusions:, These findings indicate that ethanol treatment increases NF-,B,DNA binding and proinflammatory gene expression in brain slices. Ethanol-induced innate immune proinflammatory gene induction alters neurotransmission and likely contributes to alcoholic neurodegeneration. [source]

    Key Role of Ethanol-Derived Acetaldehyde in the Motivational Properties Induced by Intragastric Ethanol: A Conditioned Place Preference Study in the Rat

    ALCOHOLISM, Issue 2 2008
    Alessandra T. Peana
    Background:, Acetaldehyde (ACD), the first metabolite of ethanol (EtOH), is produced peripherally by gastric and hepatic alcohol dehydrogenase (ADH) and centrally by brain catalase. In spite of the aversive properties classically ascribed to ACD, it has recently been suggested that ACD might mediate some of the motivational effects of EtOH. Accordingly, the relative role of ACD in the positive motivational properties of EtOH ingested is increasingly becoming the matter of debate. Thus, we studied the ability of intragastrically administered EtOH, ACD and EtOH-derived ACD to induce conditioned place preference (cpp) in rats. Methods:, Wistar rats were pretreated intraperitoneally with saline, the peripheral competitive inhibitor of ADH, 4-methylpyrazole (4-MP, 22.5, 45 or 67.5 mg/kg) or with the selective ACD-sequestrating agent, d -penicillamine (DP, 25 or 50 mg/kg), before the intragastric administration of saline, EtOH (0.5, 1 or 2 g/kg) or ACD (10, 20, or 40 mg/kg). The specificity of 4-MP and DP effects was addressed using morphine-induced cpp (2.5 mg/kg). Results:, Both, EtOH and ACD dose-dependently induced cpp; further, while EtOH-induced cpp was prevented by the administration of 4-MP and by DP, ACD-induced cpp was unaltered by 4-MP administration and prevented by DP. Both pretreatments did not interfere with morphine-induced cpp indicating that 4-MP and DP specifically modulate the motivational properties of EtOH and ACD. Conclusion:, The ability of 4-MP and DP to decrease EtOH-induced cpp suggests that a reduction of ACD levels is crucial in depriving EtOH from its motivational properties as indexed by the cpp procedure. In addition, this conclusion is supported by the inefficacy of 4-MP in preventing ACD-induced cpp, and by its blockade observed after administration of the selective ACD sequestrating agent DP. The present results underscore the role of EtOH-derived ACD in EtOH-induced motivational properties as well as its abuse liability. [source]

    Pulse EPR Spectroscopy Reveals the Coordination Sphere of Copper(II) Ions in the 1,16 Amyloid-, Peptide: A Key Role of the First Two N-Terminus Residues,

    ANGEWANDTE CHEMIE, Issue 49 2009
    Pierre Dorlet Dr.
    Ligandensphäre aufgedeckt: Cu-Ionen sollen an der Aggregation des Amyloid-,-Peptids bei Alzheimer beteiligt sein, die eindeutige Identifizierung der Cu-Liganden ist jedoch schwierig. Mit EPR- und Isotopenmarkierungstechniken wurden nun die CuII -Liganden der beiden Komplexe, die bei physiologischen pH-Werten vorliegen, ermittelt (siehe Diagramme und Strukturen). Die ersten beiden Aminosäuren des Peptids sind für die Koordination und wahrscheinlich die Aggregation wichtig. [source]

    Nanotechnology Plays a Key Role in the Development of New Energy Systems

    Ulrich Buller Prof.
    No abstract is available for this article. [source]

    Vitamin D Receptor: Key Roles in Bone Mineral Pathophysiology, Molecular Mechanism of Action, and Novel Nutritional Ligands,

    Peter W Jurutka
    Abstract The vitamin D hormone, 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], binds with high affinity to the nuclear vitamin D receptor (VDR), which recruits its retinoid X receptor (RXR) heterodimeric partner to recognize vitamin D responsive elements (VDREs) in target genes. 1,25(OH)2D3 is known primarily as a regulator of calcium, but it also controls phosphate (re)absorption at the intestine and kidney. Fibroblast growth factor 23 (FGF23) is a phosphaturic hormone produced in osteoblasts that, like PTH, lowers serum phosphate by inhibiting renal reabsorption through Npt2a/Npt2c. Real-time PCR and reporter gene transfection assays were used to probe VDR-mediated transcriptional control by 1,25(OH)2D3. Reporter gene and mammalian two-hybrid transfections, plus competitive receptor binding assays, were used to discover novel VDR ligands. 1,25(OH)2D3 induces FGF23 78-fold in osteoblasts, and because FGF23 in turn represses 1,25(OH)2D3 synthesis, a reciprocal relationship is established, with FGF23 indirectly curtailing 1,25(OH)2D3 -mediated intestinal absorption and counterbalancing renal reabsorption of phosphate, thereby reversing hyperphosphatemia and preventing ectopic calcification. Therefore, a 1,25(OH)2D3,FGF23 axis regulating phosphate is comparable in importance to the 1,25(OH)2D3,PTH axis that regulates calcium. 1,25(OH)2D3 also elicits regulation of LRP5, Runx2, PHEX, TRPV6, and Npt2c, all anabolic toward bone, and RANKL, which is catabolic. Regulation of mouse RANKL by 1,25(OH)2D3 supports a cloverleaf model, whereby VDR-RXR heterodimers bound to multiple VDREs are juxtapositioned through chromatin looping to form a supercomplex, potentially allowing simultaneous interactions with multiple co-modulators and chromatin remodeling enzymes. VDR also selectively binds certain ,3/,6 polyunsaturated fatty acids (PUFAs) with low affinity, leading to transcriptionally active VDR-RXR complexes. Moreover, the turmeric-derived polyphenol, curcumin, activates transcription of a VDRE reporter construct in human colon cancer cells. Activation of VDR by PUFAs and curcumin may elicit unique, 1,25(OH)2D3 -independent signaling pathways to orchestrate the bioeffects of these lipids in intestine, bone, skin/hair follicle, and other VDR-containing tissues. [source]

    Key role of selective viral-induced mortality in determining marine bacterial community composition

    T. Bouvier
    Summary Viral infection is thought to play an important role in shaping bacterial community composition and diversity in aquatic ecosystems, but the strength of this interaction and the mechanisms underlying this regulation are still not well understood. The consensus is that viruses may impact the dominant bacterial strains, but there is little information as to how viruses may affect the less abundant taxa, which often comprise the bulk of the total bacterial diversity. The potential effect of viruses on the phylogenetic composition of marine bacterioplankton was assessed by incubating marine bacteria collected along a North Pacific coastal-open ocean transect in seawater that was greatly depleted of ambient viruses. The ambient communities were dominated by typical marine groups, including alphaproteobacteria and the Bacteroidetes. Incubation of these communities in virus-depleted ambient water yielded an unexpected and dramatic increase in the relative abundance of bacterial groups that are generally undetectable in the in situ assemblages, such as betaproteobacteria and Actinobacteria. Our results suggest that host susceptibility is not necessarily only proportional to its density but to other characteristics of the host, that rare marine bacterial groups may be more susceptible to viral-induced mortality, and that these rare groups may actually be the winners of competition for resources. These observations are not inconsistent with the ,phage kills the winner' hypothesis but represent an extreme and yet undocumented case of this paradigm, where the potential winners apparently never actually develop beyond a very low abundance threshold in situ. We further suggest that this mode of regulation may influence not just the distribution of single strains but of entire phylogenetic groups. [source]

    Key role for enkephalinergic tone in cortico,striatal,thalamic function

    Marylou V. Solbrig
    Whereas the role of dopaminergic tone in the cortico-striatal-thalamic system is well-established, the role of endogenous opioids in the function of this system is less understood. We show that Borna disease virus infection of adult rats results in an increase in preproenkephalin transcripts in the striatum of Borna-infected rats, a region important for forming coordinated sequential motor actions and in developing programmes of thought and motivation. Stereotypic behaviours and dyskinesias, the clinical hallmarks of infection in adult Lewis rats (BD rats), are accompanied by a disrupted pattern of immediate early gene c-fos activation in the motor thalamus, with significance for the breakdown in coordinated sequential motor actions. We also find increased preproenkephalin in infected cultured neuroblastoma and rat foetal glial cells. The expression pattern of enkephalin mRNA in vivo and in vitro suggest that increased enkephalin function is one of the neuropharmacological means by which Borna disease virus causes motor disease of animals and possibly cognitive and affective disease in man, and further suggest that enkephalins play a critical role in the maintenance of a balanced tone of activity in the cortico-basal ganglia-thalamo-cortical loops. [source]

    Key role of proline-rich tyrosine kinase 2 in interleukin-8 (CXCL8/IL-8)-mediated human neutrophil chemotaxis

    IMMUNOLOGY, Issue 4 2004
    Vito Di Cioccio
    Summary The signalling pathways leading to CXCL8/IL-8-induced human neutrophil migration have not been fully characterized. The present study demonstrates that CXCL8 induces tyrosine phosphorylation as well as enzymatic activity of proline-rich tyrosine kinase 2 (Pyk2), a non-receptor protein tyrosine kinase (PTK), in human neutrophils. Induction of Pyk2 tyrosine phosphorylation by CXCL8 is regulated by Src PTK activation, whereas it is unaffected by phosphatidylinositol 3-kinase activation. Inhibition of Pyk2 activation by PP1, a Src PTK inhibitor, is paralleled by the inhibition of CXCL8-mediated neutrophil chemotaxis. Among CXCL8 receptors, Src protein tyrosine kinase activation selectively regulates CXCR1-mediated polymorphonuclear neutrophil (PMN) chemotaxis. Overexpression of PykM, the kinase-dead mutant of Pyk2, blocks CXCL8-induced chemotaxis of HL-60-derived PMN-like cells, thus pinpointing the key role of Pyk2 in CXCL8-induced chemotaxis. [source]

    From bacterial avirulence genes to effector functions via the hrp delivery system: an overview of 25 years of progress in our understanding of plant innate immunity

    SUMMARY Cloning the first avirulence (avr) gene has led not only to a deeper understanding of gene-for-gene interactions in plant disease, but also to fundamental insights into the suppression of basal defences against microbial attack. This article (focusing on Pseudomonas syringae) charts the development of ideas and research progress over the 25 years following the breakthrough achieved by Staskawicz and coworkers. Advances in gene cloning technology underpinned the identification of both avr and hrp genes, the latter being required for the activation of the defensive hypersensitive reaction (HR) and pathogenicity. The delivery of Avr proteins through the type III secretion machinery encoded by hrp gene clusters was demonstrated, and the activity of the proteins inside plant cells as elicitors of the HR was confirmed. Key roles for avr genes in pathogenic fitness have now been established. The rebranding of Avr proteins as effectors, proteins that suppress the HR and cell wall-based defences, has led to the ongoing search for their targets, and is generating new insights into the co-ordination of plant resistance against diverse microbes. Bioinformatics-led analysis of effector gene distribution in genomes has provided a remarkable view of the interchange of effectors and also their functional domains, as the arms race of attack and defence drives the evolution of microbial pathogenicity. The application of our accrued knowledge for the development of disease control strategies is considered. [source]

    Key safety roles in organizational changes

    Paul A. Davidson
    Abstract As, business moves to lean manufacture to minimize costs, it inherently leads to reduced staff and a flatter management structure. During these organizational changes, it is important that safety is not compromised by the removal of key people. A number of layers of controls and defenses are put in place, to both prevent an event and to mitigate the consequences if an event occurs. There are many competing techniques for assessing the impact of organizational change, each of which has its pros and cons. This article discusses a technique based on the use of the Bow Tie methodology to analyze major accident scenarios for a high-hazard site, and presents an example from a real life case study. Controls identified in the analysis have a responsible person assigned to them and a summary of these roles is used to define the impact of removing a role. Key roles for safety controls are maintained and any eliminated roles have their responsibilities reassigned. After the change, final role descriptions would specifically include descriptions of key safety control responsibilities. Within this article, we have discussed the application of the Bow Tie technique to Organizational Change on a site during a 15% staff reduction. This application and technique is easily followed, leading to identification and correction of gaps in the management systems. © 2009 American Institute of Chemical Engineers Process Saf Prog, 2010 [source]

    Geometric algebra and transition-selective implementations of the controlled-NOT gate

    Timothy F. Havel
    Geometric algebra provides a complete set of simple rules for the manipulation of product operator expressions at a symbolic level, without any explicit use of matrices. This approach can be used not only to describe the state and evolution of a spin system, but also to derive the effective Hamiltonian and associated propagator in full generality. In this article, we illustrate the use of geometric algebra via a detailed analysis of transition-selective implementations of the controlled-NOT gate, which plays a key role in NMR-based quantum information processing. In the appendices, we show how one can also use geometric algebra to derive tight bounds on the magnitudes of the errors associated with these implementations of the controlled-NOT. © 2004 Wiley Periodicals, Inc. Concepts Magn Reson Part A 23A: 49,62, 2004 [source]

    Babylon: middleware for distributed, parallel, and mobile Java applications

    Willem van Heiningen
    Abstract Babylon is a collection of tools and services that provide a 100% Java-compatible environment for developing, running and managing parallel, distributed and mobile Java applications. It incorporates features such as object migration, asynchronous method invocation, and remote class loading, while providing an easy-to-use interface. Additionally, Babylon enables Java applications to seamlessly create and interact with remote objects, while protecting those objects from other applications by implementing access restrictions and separate namespaces. The implementation of Babylon centers around dynamic proxies, a feature first available in Java 1.3, that allow proxy objects to be created at runtime. Dynamic proxies play a key role in achieving the goals of Babylon. The potential cluster computing benefits of the system are demonstrated with experimental results, which show that sequential Java applications can achieve significant performance benefits from using Babylon to parallelize their work across a cluster of workstations. Copyright © 2008 John Wiley & Sons, Ltd. [source]

    Experimental analysis of a mass storage system

    Shahid Bokhari
    Abstract Mass storage systems (MSSs) play a key role in data-intensive parallel computing. Most contemporary MSSs are implemented as redundant arrays of independent/inexpensive disks (RAID) in which commodity disks are tied together with proprietary controller hardware. The performance of such systems can be difficult to predict because most internal details of the controller behavior are not public. We present a systematic method for empirically evaluating MSS performance by obtaining measurements on a series of RAID configurations of increasing size and complexity. We apply this methodology to a large MSS at Ohio Supercomputer Center that has 16 input/output processors, each connected to four 8 + 1 RAID5 units and provides 128 TB of storage (of which 116.8 TB are usable when formatted). Our methodology permits storage-system designers to evaluate empirically the performance of their systems with considerable confidence. Although we have carried out our experiments in the context of a specific system, our methodology is applicable to all large MSSs. The measurements obtained using our methods permit application programmers to be aware of the limits to the performance of their codes. Copyright © 2006 John Wiley & Sons, Ltd. [source]

    Nitric oxide bioavailability modulates the dynamics of microvascular oxygen exchange during recovery from contractions

    ACTA PHYSIOLOGICA, Issue 2 2010
    D. M. Hirai
    Abstract Aim:, Lowered microvascular PO2 (PO2mv) during the exercise off-transient likely impairs muscle metabolic recovery and limits the capacity to perform repetitive tasks. The current investigation explored the impact of altered nitric oxide (NO) bioavailability on PO2mv during recovery from contractions in healthy skeletal muscle. We hypothesized that increased NO bioavailability (sodium nitroprusside: SNP) would enhance PO2mv and speed its recovery kinetics while decreased NO bioavailability (l -nitro arginine methyl ester: l -NAME) would reduce PO2mv and slow its recovery kinetics. Methods:,PO2mv was measured by phosphorescence quenching during transitions (rest,1 Hz twitch-contractions for 3 min,recovery) in the spinotrapezius muscle of Sprague,Dawley rats under SNP (300 ,m), Krebs-Henseleit (Control) and l -NAME (1.5 mm) superfusion conditions. Results:, Relative to recovery in Control, SNP resulted in greater overall microvascular oxygenation as assessed by the area under the PO2mv curve (PO2 AREA; Control: 3471 ± 292 mmHg s; SNP: 4307 ± 282 mmHg s; P < 0.05) and faster off-kinetics as evidenced by the mean response time (MRToff; Control: 60.2 ± 6.9 s; SNP: 34.8 ± 5.7 s; P < 0.05), whereas l -NAME produced lower PO2 AREA (2339 ± 444 mmHg s; P < 0.05) and slower MRToff (86.6 ± 14.5 s; P < 0.05). Conclusion:, NO bioavailability plays a key role in determining the matching of O2 delivery-to-O2 uptake and thus the upstream O2 pressure driving capillary-myocyte O2 flux (i.e. PO2mv) following cessation of contractions in healthy skeletal muscle. Additionally, these data support a mechanistic link between reduced NO bioavailability and prolonged muscle metabolic recovery commonly observed in ageing and diseased populations. [source]

    Priority Wetland Invertebrates as Conservation Surrogates

    agua dulce; caracoles; conservación; especies paraguas; especies sustitutas; gasterópodos Abstract:,Invertebrates are important functionally in most ecosystems, but seldom appraised as surrogate indicators of biological diversity. Priority species might be good candidates; thus, here we evaluated whether three freshwater invertebrates listed in the U.K. Biodiversity Action Plan indicated the richness, composition, and conservation importance of associated wetland organisms as defined respectively by their alpha diversity, beta diversity, and threat status. Sites occupied by each of the gastropods Segmentina nitida, Anisus vorticulus, and Valvata macrostoma had greater species richness of gastropods and greater conservation importance than other sites. Each also characterized species assemblages associated with significant variations between locations in alpha or beta diversity among other mollusks and aquatic macrophytes. Because of their distinct resource requirements, conserving the three priority species extended the range of wetland types under management for nature conservation by 18% and the associated gastropod niche-space by around 33%. Although nonpriority species indicated variations in richness, composition, and conservation importance among other organisms as effectively as priority species, none characterized such a wide range of high-quality wetland types. We conclude that priority invertebrates are no more effective than nonpriority species as indicators of alpha and beta diversity or conservation importance among associated organisms. Nevertheless, conserving priority species can extend the array of distinct environments that are protected for their specialized biodiversity and environmental quality. We suggest that this is a key role for priority species and conservation surrogates more generally, and, on our evidence, can best be delivered through multiple species with contrasting habitat requirements. Resumen:,Los invertebrados son funcionalmente importantes en la mayoría de los ecosistemas, pero raramente son valorados como indicadores sustitutos de la diversidad biológica. Las especies prioritarias pueden ser buenos candidatos; por lo tanto, aquí evaluamos sí tres especies de invertebrados enlistados en el Plan de Acción para la Biodiversidad del Reino Unido eran indicadores de la riqueza, la composición e importancia para la conservación de organismos de humedal asociados definida por su diversidad alfa, diversidad beta y estatus de amenaza respectivamente. Los sitios ocupados por cada uno de los gasterópodos Segmentina nitida, Anisus vorticulus and Valvata macrostoma tuvieron una mucho mayor riqueza de gasterópodos y mayor importancia para la conservación que otros sitios. Cada uno también caracterizó a los ensambles asociados con variaciones significativas entre localidades en la diversidad alfa o entre otros moluscos y macrofitas acuáticas en la diversidad beta. Debido a sus diferentes requerimientos de recursos, la conservación de las tres especies prioritarias se amplió la extensión de todos los tipos de humedal bajo manejo para la conservación de la naturaleza en 18% y el nicho-espacio de los gasterópodos asociados se amplió alrededor de 33%. Aunque las especies no prioritarias indicaron variaciones en riqueza, composición e importancia de conservación entre otros organismos tan efectivamente como las especies prioritarias, ninguna caracterizó un rango tan amplio de humedales de alta calidad. Concluimos que los invertebrados prioritarios no son más efectivos que las especies no prioritarias como indicadores de la diversidad alfa y beta ni de la importancia para la conservación entre organismos asociados. Sin embargo, la conservación de especies prioritarias puede ampliar el conjunto de ambientes diferentes que son protegidos por su biodiversidad especializada y calidad ambiental. Sugerimos que este es un papel clave para las especies prioritarias y, más generalmente, para los sustitutos de conservación, y, con base en nuestra evidencia, puede ser desarrollado mediante múltiples especies con requerimientos de hábitat contrastantes. [source]

    A decade of hypocretins: past, present and future of the neurobiology of arousal

    ACTA PHYSIOLOGICA, Issue 3 2010
    L. De Lecea
    Abstract In 1998, two groups independently identified the hypocretins, also known as orexins, as two hypothalamic peptides derived from the same precursor expressed in a few thousand neurones restricted to the perifornical area. A decade later, an amazing set of discoveries has demonstrated a key role for this neurotransmitter system in arousal and beyond. Here I review some of the experiments that led to these discoveries and the implications in the neurobiology of the hypothalamus and our understanding of brain arousal. [source]

    Independence Threats, Litigation Risk, and the Auditor's Decision Process,

    Allen D. Blay
    Abstract This study examines the effect of independence threats and litigation risk on auditors' evaluation of information and subsequent reporting choices. Using a Web-based experiment, I tracked auditors' information gathering and evaluation leading to a going-concern reporting decision. Specifically, 48 audit managers assessed client survival likelihood, gathered additional information, and suggested audit report choices. I found that auditors facing high independence threats (fear of losing the client) evaluated information as more indicative of a surviving client and were more likely to suggest an unmodified audit report, consistent with client preferences. In contrast, auditors facing high litigation risk evaluated information as more indicative of a failing client and were more likely to suggest a modified audit report. In addition, the association between risk and report choice was fully mediated by final information evaluation. This suggests that it is unlikely that different reporting choices resulted from a conscious choice bias, but rather that motivated reasoning during evidence evaluation plays a key role in the effect of risk in auditor decision making. [source]

    Development and validation of a smoothing-splines-based correction method for improving the analysis of CEST-MR images

    J. Stancanello
    Abstract Chemical exchange saturation transfer (CEST) imaging is an emerging MRI technique relying on the use of endogenous or exogenous molecules containing exchangeable proton pools. The heterogeneity of the water resonance frequency offset plays a key role in the occurrence of artifacts in CEST-MR images. To limit this drawback, a new smoothing-splines-based method for fitting and correcting Z -spectra in order to compensate for low signal-to-noise ratio (SNR) without any a priori model was developed. Global and local voxel-by-voxel Z -spectra were interpolated by smoothing splines with smoothing terms aimed at suppressing noise. Thus, a map of the water frequency offset (,zero' map) was used to correctly calculate the saturation transfer (ST) for each voxel. Simulations were performed to compare the method to polynomials and zero-only-corrected splines on the basis of SNR improvement. In vitro acquisitions of capillaries containing solutions of LIPOCEST agents at different concentrations were performed to experimentally validate the results from simulations. Additionally, ex vivo investigations of bovine muscle mass injected with LIPOCEST agents were performed as a function of increasing pulse power. The results from simulations and experiments highlighted the importance of a proper ,zero' correction (15% decrease of fictitious CEST signal in phantoms and ex vivo preparations) and proved the method to be more accurate compared with the previously published ones, often providing a SNR higher than 5 in different simulated and experimentally noisy conditions. In conclusion, the proposed method offers an accurate tool in CEST investigation. Copyright © 2008 John Wiley & Sons, Ltd. [source]

    An innovative model to promote CSR among SMEs operating in industrial clusters: evidence from an EU project

    Massimo Battaglia
    Abstract This paper presents the findings of our EU co-funded project, an idea developed to better understand the opportunities to formalize corporate social responsibility (CSR) practices for small and medium enterprises (SMEs) in a clustered system. Small companies often have to compete in a global market; for this reason, cooperation among SMEs, and with local stakeholders and intermediary institutions, might be facilitated by a collective answer to new market requests. Cooperation and social capital are key elements to facilitate trust amongst involved local actors. Moreover, they can also play a key role in the formalization of CSR policies and practices for small companies. In our project, we aimed at identifying and understanding the role of the ,intermediary institutions' (such as trade unions, local authorities, business consortia) in the cluster. Throughout the paper, we focus on the analysis of three industrial clusters in Tuscany (Italy). Copyright © 2010 John Wiley & Sons, Ltd and ERP Environment. [source]

    Trust and Innovation: from Spin-Off Idea to Stock Exchange

    Marko Kohtamäki
    Trust among entrepreneurs, their co-workers and between the entrepreneurs and their business partners plays a key role in the early stages of formation of a new company. In this piece of research, trust is defined as a belief consisting of eight trusting beliefs, emphasising the rational consideration between these beliefs and other situational factors. The concept of trust is developed through objects, mechanisms and antecedents. The present paper is an empirical exploration of these phenomena in the context of innovativeness in a high-tech company. The goal is to describe the role, content and impact of trust at the different stages of a business evolution process. [source]


    CRIMINOLOGY, Issue 1 2006
    Much of the research focusing on conventional occupations concludes that mentored individuals are more successful in their careers than those who are not mentored. Early research in criminology made a similar claim. Yet contemporary criminology has all but ignored mentors. We investigate this oversight, drawing on Sutherland's insights on tutelage and criminal maturation and incorporating ideas on human and social capital. We argue that mentors play a key role in their protégés' criminal achievements and examine this hypothesis with data from a recent survey of incarcerated adult male offenders in the Canadian province of Quebec. In this sample, a substantial proportion of respondents reported the presence of an influential individual in their lives who introduced them to a criminal milieu and whom they explicitly regarded as a mentor. After studying the attributes of offenders and their mentors, we develop a causal framework that positions criminal mentor presence within a pathway that leads to greater benefits and lower costs from crime. [source]


    Research Summary: "Right-to-Carry" (RTC) concealed-handgun laws mandate that authorities issue concealed handgun permits to qualified applicants. The supposition by those supporting the laws is that allowing private citizens to carry concealed handguns in public can reduce violent crime by deterring prospective criminals afraid of encountering armed civilians. Critics of the laws argue that violent altercations are more likely to turn deadly when more people carry guns. Whether the laws cause violent crime to increase or to decrease has become an important public policy question, as most states have now adopted such legislation. The present study evaluates Florida's 1987 RTC law, which prior research suggests plays a key role in the RTC debate. Specifically, we use panel data for 58 Florida counties from 1980 to 2000 to examine the effects on violent crime from increases in the number of people with concealed-carry permits, rather than before-after dummy and time-trend variables used in prior research. We also address many of the methodological problems encountered in earlier RTC studies. We present numerous model specifications, and we find little evidence that increases in the number of citizens with concealed-handgun permits reduce or increase rates of violent crime. Policy Implications: The main policy implication of this research is that there appears to be little gained in the way of crime prevention by converting restrictive gun carrying laws to "shall-issue" laws, although the laws might still prove beneficial by (1) eliminating arbitrary decisions on gun permit applications, (2) encouraging gun safety, (3) making permit holders feel safer when out in public, (4) providing permit holders with a more effective means of self-defense, and (5) reducing the costs to police departments of enforcing laws prohibiting unlicensed gun carrying. [source]

    Crystal structure of a ternary mononuclear copper (II) complex: 4-chloro-3-methyl-6[(N-2-picolyl)-1,-iminomethyl]phenolato copper(II)perchlorate

    S. M. Malathy Sony
    Abstract The complex crystallizes in monoclinic space group P21/n with unit cell parameters a = 7.295(4), b = 19.627(5), c = 12.770(4) Å, , = 101.25(4)º, V = 1793.2(12) Å3, Z = 4, , = 1.684 Mg/m3 at T = 293(2)K. The structure was solved by Patterson method and refined by full-matrix least-squares procedures to final R = 0.0387 using 2906 observed reflections. The asymmetric unit of the complex contains a mononuclear tridentate ligand, a perchlorate group and a methanol molecule. The compound crystallizes as parallel layers of polymeric complex bridged through perchloarate groups. The molecular CuN2OO,O,,2 chromophore involves an elongated rhombic octahedral structure and the Cu-ligand bond shows greater disparity. The five-membered chelate ring and the pyridine ring lie in the same plane while the six membered chelate ring assumes sofa conformation. A strong O-H,O inter molecular interaction plays a key role in the formation of dimer along b-axis. (© 2006 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim) [source]

    Rho plays a central role in regulating local cell-matrix mechanical interactions in 3D culture

    CYTOSKELETON, Issue 6 2007
    N. Lakshman
    Abstract The purpose of this study was to assess quantitatively the role of the small GTPase Rho on cell morphology, f-actin organization, and cell-induced matrix remodeling in 3D culture. Human corneal fibroblasts (HTK) were infected with adenoviruses that express green fluorescent protein (GFP) or GFP-N19Rho (dominant negative Rho). One day later cells were plated inside collagen matrices and allowed to spread for 24 h. Cells were fixed and stained for f-actin. Fluorescent (for f-actin) and reflected light (for collagen fibrils) images were acquired using confocal microscopy. Fourier transform analysis was used to assess local collagen fibril alignment, and changes in cell morphology and collagen density were measured using MetaMorph. The decrease in matrix height was used as an indicator of global matrix contraction. HTK and HTK-GFP cells induced significant global matrix contraction; this was inhibited by N19Rho. HTK and HTK-GFP fibroblasts generally had a bipolar morphology and occasional intracellular stress fibers. Collagen fibrils were compacted and aligned parallel to stress fibers and pseudopodia. In contrast, HTK-GFPN19 cells were elongated, and had a more cortical f-actin distribution. Numerous small extensions were also observed along the cell body. In addition, both local collagen fibril density and alignment were significantly reduced. Rho plays a key role in regulating both the morphology and mechanical behavior of corneal fibroblasts in 3D culture. Overall, the data suggest that Rho-kinase dependent cell contractility contributes to global and local matrix remodeling, whereas Rho dependent activation of mDia and/or other downstream effectors regulates the structure and number of cell processes. Cell Motil. Cytoskeleton 2007. © 2007 Wiley-Liss, Inc. [source]

    Second- and third-generation antihistamines in the treatment of urticaria

    Anne K. Ellis
    ABSTRACT: Chronic urticaria is mainly idiopathic in nature and can be difficult to treat. While less responsive to antihistamine therapy than acute urticaria, antihistamines still play a key role in the management of symptomatology. While many of the antihistamines still commonly used to treat urticaria are first generation H1 antagonists (e.g., diphenhydramine, hydroxyzine), the more recently developed second-generation agents (e.g., loratadine, cetirizine) and their metabolites,the third-generation antihistamines (e.g., fexofenadine, norastemizole, descarboxyloratadine),possess many of the desirable clinical effects of the first-generation agents with a more tolerable side effect profile. This review discusses the advantages and disadvantages of each of the various second- and third-generation agents available, and presents some of the data showing the differences among these agents in the treatment of chronic urticaria. [source]

    Globalization from Below: Free Software and Alternatives to Neoliberalism

    Sara Schoonmaker
    ABSTRACT This article explores one of the central struggles over the politics of globalization: forging alternatives to neoliberalism by developing new forms of globalization from below. It focuses on a unique facet of this struggle, rooted in the centrality of information technologies for global trade and production, as well as new forms of media and digital culture. The analysis has four main parts: examining the key role of software as a technological infrastructure for diverse forms of globalization; conceptualizing the contradictory implications of three software business models for realizing the utopian potential of digital technology to develop forms of globalization from below; exploring how three free and open source software business models were put into practice by Red Hat, IBM and the Free Software Foundation; and analysing Brazilian software policy as a form of globalization from below that challenges the historical dominance of the global North and seeks to develop new forms of digital inclusion and digital culture. [source]

    Differentiation inducing factors in Dictyostelium discoideum: A novel low molecular factor functions at an early stage(s) of differentiation

    Akiko A. Oohata
    There are reports that secreted factor(s) are involved in prespore cell differentiation in Dictyostelium discoideum, but the structures and functions of the various factors have not been elucidated. Previously, we described two prespore cell-inducing factors in conditioned medium; one was a glycoprotein named prespore cell-inducing factor (, factor, or PSI-1), and the other, a heat stable dialyzable factor(s). In the present paper, we purified and characterized the most potent prespore cell-inducing activity in dialysates. The factor began to be secreted after the onset of starvation and stopped being secreted once the cells had aggregated, which was earlier than the onset of the , factor gene expression. In addition, unlike , factor, its secretion did not appear to depend on activation of protein kinase A. Interestingly, the purified factor not only induced prespore cell specific genes such as pspA and cotC but also a prestalk-cell specific gene, ecmB in vitro. The purified factor is tentatively designated polyketide-like factor (PLF), because it seems to be a novel polyketide with 208 Da. Half maximal induction of prespore cell was obtained with 26 nmol/L of PLF. We propose that PLF plays a key role in the acquisition of differentiation commitment, before the , factor induces specifically prespore cell differentiation. [source]

    Brachyury -downstream notochord genes and convergent extension in Ciona intestinalis embryos

    Kohji Hotta
    Formation of the chordate body is accomplished by a complex set of morphogenetic movements including convergent extension of notochord cells. In the ascidian Ciona intestinalis, Brachyury plays a key role in the formation of the notochord, and more than 30 Bra-downstream notochord genes have been identified. In the present study, we examined the effects of functional suppression of nine Bra -downstream notochord genes, which include Ci-PTP, Ci-ACL, Ci-prickle, Ci-netrin, Ci-trop, Ci-Noto3, Ci-ASAK, Ci-ERM and Ci-pellino. When the function of the first two genes (Ci-PTP and Ci-ACL) was suppressed with specific morpholinos, the notochord cells failed to converge, while functional suppression of Ci-prickle resulted in a failure of intercalation, and therefore the cells in these three types of embryo remained in the mid-dorsal region of the embryo. Functional suppression of the next four genes (Ci-netrin, Ci-trop, Ci-Noto3 and Ci-ASAK) resulted in the partial defect of intercalation, and the notochord did not consist of a single row. In addition, when the function of the last two genes (Ci-ERM and Ci-pellino) was suppressed, notochord cells failed to elongate in the embryo, even though convergence/extension took place normally. These results indicate that many Bra -downstream notochord genes are involved in convergence/extension of the embryo. [source]

    General measures of cognition for the preschool child

    Elizabeth O. LichtenbergerArticle first published online: 13 SEP 200
    Abstract Preschool-age children who are experiencing delays in physical, cognitive, communication, social, emotional, or adaptive development are often referred for a comprehensive assessment to make diagnostic determinations and to help develop appropriate interventions. Typically cognitive assessment has a key role in a comprehensive evaluation of a young child. In this article, five individually administered tests of cognitive ability, normed for the preschool-age child, are reviewed. These specific tests include the Bayley Scales of Infant Development, 2nd edition, the Kaufman Assessment Battery for Children, 2nd edition, the Wechsler Preschool and Primary Scale of Intelligence, 3rd edition, the Stanford-Binet Intelligence Scale, 5th edition, and the Differential Abilities Scales. The following is provided for these cognitive instruments: a description of the test procedures, information on scoring systems, highlights of the technical qualities, and a summary of the general meaning of test results. The article concludes with strengths and limitations of the instruments. © 2005 Wiley-Liss, Inc. MRDD Research Reviews 2005;11:197,208. [source]