bluuebunny/crossref_metadata_2025 huggingface dataset:
Glucocorticoids Activate Cardiac Mineralocorticoid Receptors During Experimental Myocardial Infarction
Authors: Mihailidou Anastasia S. , Loan Le Thi Yen , Mardini Mahidi , Funder John W.
Published: October 2009

Myocardial ischemia-reperfusion leads to significant changes in redox state, decreased postischemic functional recovery, and cardiomyocyte apoptosis, with development and progression of heart failure. Ischemia-reperfusion in the isolated perfused rat heart has been used as a model of heart failure. Clinically, mineralocorticoid receptor blockade in heart failure decreases morbidity and mortality versus standard care alone. The effects of corticosteroids on infarct area and apoptosis were determined in rat hearts subjected to 30 minutes of ischemia and 2.5 hours of reperfusion. Both aldosterone and cortisol increased infarct area and apoptotic index, an effect half-maximal between 1 and 10 nM and reversed by spironolactone. Dexamethasone and mifepristone aggravated infarct area and apoptotic index, similarly reversed by spironolactone. Spironolactone alone reduced infarct area and apoptotic index below ischemia-reperfusion alone, in hearts from both intact and adrenalectomized rats. The present study shows that cardiac damage is aggravated by activation of mineralocorticoid receptors by aldosterone or cortisol or of glucocorticoid receptors by dexamethasone. Mifepristone unexpectedly acted as a glucocorticoid receptor agonist, for which there are several precedents. Spironolactone protected cardiomyocytes via inverse agonist activity at mineralocorticoid receptors, an effect near maximal at a relatively low dose (10 nM). Spironolactone acts not merely by excluding corticosteroids from mineralocorticoid receptors but as a protective inverse agonist at low concentration. Mineralocorticoid receptor antagonists may, thus, provide an additional therapeutic advantage in unstable angina and acute myocardial infarction.
How to Modify a Neural Network Gradually Without Changing Its Input-Output Functionality
Authors: DiMattina Christopher , Zhang Kechen
Published: October 2009

It is generally unknown when distinct neural networks having different synaptic weights and thresholds implement identical input-output transformations. Determining the exact conditions for structurally distinct yet functionally equivalent networks may shed light on the theoretical constraints on how diverse neural circuits might develop and be maintained to serve identical functions. Such consideration also imposes practical limits on our ability to uniquely infer the structure of underlying neural circuits from stimulus-response measurements. We introduce a biologically inspired mathematical method for determining when the structure of a neural network can be perturbed gradually while preserving functionality. We show that for common three-layer networks with convergent and nondegenerate connection weights, this is possible only when the hidden unit gains are power functions, exponentials, or logarithmic functions, which are known to approximate the gains seen in some biological neurons. For practical applications, our numerical simulations with finite and noisy data show that continuous confounding of parameters due to network functional equivalence tends to occur approximately even when the gain function is not one of the aforementioned three types, suggesting that our analytical results are applicable to more general situations and may help identify a common source of parameter variability in neural network modeling.
Spiking Neuron Model for Temporal Sequence Recognition
Authors: Byrnes Sean , Burkitt Anthony N. , Grayden David B. , Meffin Hamish
Published: October 2009

A biologically inspired neuronal network that stores and recognizes temporal sequences of symbols is described. Each symbol is represented by excitatory input to distinct groups of neurons (symbol pools). Unambiguous storage of multiple sequences with common subsequences is ensured by partitioning each symbol pool into subpools that respond only when the current symbol has been preceded by a particular sequence of symbols. We describe synaptic structure and neural dynamics that permit the selective activation of subpools by the correct sequence. Symbols may have varying durations of the order of hundreds of milliseconds. Physiologically plausible plasticity mechanisms operate on a time scale of tens of milliseconds; an interaction of the excitatory input with periodic global inhibition bridges this gap so that neural events representing successive symbols occur on this much faster timescale. The network is shown to store multiple overlapping sequences of events. It is robust to variation in symbol duration, it is scalable, and its performance degrades gracefully with perturbation of its parameters.
Aspects of the Iranian Code of Islamic Punishment: The Principle of Legality and the Temporal, Spatial and Personal Applicability of the Law
Authors: Tellenbach Silvia
Published: October 2009

Iran declares itself an Islamic Republic in which all laws and regulations must be based on Islamic criteria as interpreted by the Shi'ite dja-farī School. As a consequence, Islamic law has to be applied to all the everyday legal problems of a modern state of about 73 million inhabitants and, in addition, the position of Iran in the international community must be in accordance with Islamic law. This contribution deals with selected topics of criminal law looking at the solutions that exist in Iranian criminal law. Furthermore, it examines to what extent Islamic law as understood in Iran accepts regulations which are internationally generally applied and what are the points on which Islamic law and Western law do not reach a common understanding.
An Objective Method of Evaluating and Devising Storm-Tracking Algorithms
Authors: Lakshmanan Valliappa , Smith Travis
Published: October 2009

Although storm-tracking algorithms are a key ingredient of nowcasting systems, evaluation of storm-tracking algorithms has been indirect, labor intensive, or nonspecific. A set of easily computable bulk statistics that can be used to directly evaluate the performance of tracking algorithms on specific characteristics is introduced. These statistics are used to evaluate five widely used storm-tracking algorithms on a diverse set of radar reflectivity data cases. Based on this objective evaluation, a storm-tracking algorithm is devised that performs consistently and better than any of the previously suggested techniques.
Confidence and Leading Indicators: Introduction
Authors: Mitchell James
Published: October 2009

We are all impatient to know what is going on in the economy ‘right now’. But given the delays in the publication of official data, effectively economists are driving looking through the rear-view mirror as they do not know where the economy is until they have driven well past it. The statistical office in the UK (the ONS), for example, publishes quarterly GDP estimates about 27 days after the end of the quarter, and this is relatively quick by international standards.
A System of Rapid Estimates to Improve Real-Time Monitoring of the Economic Situation: The Case of the Euro Area
Authors: Mazzi Gian Luigi , Montana Gaetana
Published: October 2009

Timely availability of relevant economic information is from the users' point of view a crucial pre-requirement for effective economic and monetary policy and for accurate analysis and reliable forecasting. Unfortunately, official statistics are not always able to meet such needs. For this reason, particularly over the recent past, advanced statistical and econometric techniques have been used to complement the classical production process in order to increase the timeliness of the relevant economic information. Furthermore, official statistics do not necessarily show explicitly relevant phenomena such as the cyclical situation and the location of turning points. In order to fill this gap, indicators have to be built up to extract such relevant signals and to make them available in an easily readable and comprehensible way to all users. This paper gives a general overview of ongoing Eurostat projects, aiming to supply timely information to all users based on transparent and statistically sound methodologies. In particular this paper presents results related to the construction of flash estimates in order to increase the timeliness of official statistics as well as the construction of a timely statistical system for business cycle analysis based on a set of turning points indicators and cyclical estimates. The results obtained so far are very encouraging, especially in terms of the overall quality of the estimates and the statistical robustness of the proposed methods. Nevertheless, some improvements, particularly related to the precision of flash estimates, are needed, especially under an uncertain economic situation and regime changes.
Effect of Age, Weight, and CYP2C19 Genotype on Escitalopram Exposure
Authors: Jin Yuyan , Pollock Bruce G. , Frank Ellen , Cassano Giovanni B. , Rucci Paola , Müller Daniel J. , Kennedy James L. , Forgione Rocco Nicola , Kirshner Margaret , Kepple Gail , Fagiolini Andrea , Kupfer David J. , Bies Robert R.
Published: October 2009

The purpose of this study was to characterize escitalopram population pharmacokinetics (PK) in patients treated for major depression in a cross‐national, US‐Italian clinical trial. Data from the 2 sites participating in this trial, conducted at Pittsburgh (United States) and Pisa (Italy), were used. Patients received 5, 10, 15, or 20 mg of escitalopram daily for a minimum of 32 weeks. Nonlinear mixed effects modeling was used to model the PK characteristics of escitalopram. One‐ and 2‐compartment models with various random effect implementations were evaluated during model development. Objective function values and goodness‐of‐fit plots were used as model selection criteria. CYP2C19 genotype, age, weight, body mass index, sex, race, and clinical site were evaluated as possible covariates. In total, 320 plasma concentrations from 105 Pittsburgh patients and 153 plasma concentrations from 67 Pisa patients were available for the PK model development. A 1‐compartmental model with linear elimination and proportional error best described the data. Apparent clearance (CL/F) and volume of distribution (V/F) for escitalopram without including any covariates in the patient population were 23.5 L/h and 884 L, respectively. CYP2C19 genotype, weight, and age had a significant effect on CL/F, and patient body mass index affected estimated V/F. Patients from Pisa, Italy, had significantly lower clearances than patients from Pittsburgh that disappeared after controlling for patient CYP2C19 genotype, age, and weight. Postprocessed individual empirical Bayes estimates on clearance for the 172 patients show that patients without allele CYP2C19*2 or *3 (n = 82) cleared escitalopram 33.7% faster than patients with heterogeneous or homogeneous *2 or *3 (*17/*2, *17/*3, *1/*2, *1/*3, *2/*2, *2/*3, and *3/*3, n = 46). CL/F significantly decreased with increasing patient age. Patients younger than 30 years (n = 45) cleared escitalopram 20.7% and 42.7% faster than patients aged 30 to 50 years (n = 84) and older than 50 years of age (n = 43), respectively. CYP2C19 genotype, age, and weight strongly influenced the CL/F of escitalopram. These variables may affect patient tolerance of this antidepressant and may provide important information in the effort to tailor treatments to patients' individual needs.
Itraconazole and Rifampin Alter Significantly the Disposition and Antihistamine Effect of Ebastine and Its Metabolites in Healthy Participants
Authors: Shon Ji‐Hong , Yeo Chang‐Woo , Liu Kwang‐Hyeon , Lee Sang‐Seop , Cha In‐Jun , Shin Jae‐Gook
Published: October 2009

The present study was performed to elucidate the effects of itraconazole and rifampin on the pharmacokinetics and pharmacodynamics of ebastine, a nonsedative H1 receptor antagonist. In a 3‐way crossover sequential design with 2‐week washouts, 10 healthy participants were pretreated with itraconazole for 6 days, rifampin for 10 days, or neither. After oral administration of 20 mg ebastine, blood and urine samples were collected for 72 and 24 hours, respectively, and histamine‐induced wheal and flare reactions were measured to assess the antihistamine response for 12 hours. Itraconazole pretreatment decreased the oral clearance of ebastine to 10% (P < .001) and increased the AUC∞of the active metabolite, carebastine, by 3‐fold (P < .001). On the other hand, rifampin pretreatment decreased the AUC∞of carebastine to 15% (P < .001), with an enormous reduction in the oral bioavailability of ebastine and significantly reduced histamine‐induced skin reactions. From these results, the disposition of ebastine and carebastine seems to be significantly altered by coadministration of itraconazole or rifampin. The antihistamine response after ebastine dosing would be decreased following rifampin pretreatments.
All in the Family
Authors: DeLisi Matt , Beaver Kevin M. , Vaughn Michael G. , Wright John Paul
Published: October 2009

A range of Gene × Environment interactions is associated with antisocial phenotypes, and the evidence is clear that the etiology of antisocial behavior is strongly heritable and that environmental liabilities are important. However, the precise ways that genetic and environmental pathogens interact to predict antisocial behavior are underspecified. The present study shows that the interaction between a polymorphism in a dopamine receptor gene (DRD2) and a criminal father predicts five antisocial phenotypes among African American females ( n = 232) in the National Longitudinal Study of Adolescent Health. Genetic risk (as measured by the A1 allele) and a criminal father interacted to predict serious and violent delinquency at Wave 1, serious and violent delinquency at Wave 2, and number of police contacts. The current investigation represents the first study to show Gene × Environment interactions in the prediction of antisocial phenotypes using criminal justice system status as an environmental pathogen.
The Concept of “Opportunity” in Entrepreneurship Research: Past Accomplishments and Future Challenges
Authors: Short Jeremy C. , Ketchen David J. , Shook Christopher L. , Ireland R. Duane
Published: October 2009

Opportunity is a central concept within the entrepreneurship field, and there is now a critical mass of literature centered on the concept. The authors seek to make two main contributions to this literature. First, we provide a detailed review of research on the opportunity concept and the processes surrounding it, highlighting extant insights and future needs. Second, we describe ways that the entrepreneurship literature’s insights about the opportunity concept could be enhanced by research in other fields, both inside and outside business-related domains.
Relationships at Work: Toward a Multidimensional Conceptualization of Dyadic Work Relationships
Authors: Ferris Gerald R. , Liden Robert C. , Munyon Timothy P. , Summers James K. , Basik Kevin J. , Buckley M. Ronald
Published: October 2009

Work relationships have come to form the very foundation of organizations and the contemporary embodiment of how most work gets accomplished, and there has been increased scholarly interest in this area. Although research has investigated the nature of high-quality and low-quality work relationships, few attempts have taken that next important step in more precisely articulating the actual dimensions that underlie work relationships, how they relate to one another, and how, as contextual background, they frame and influence organizational phenomena. In an effort to help address this gap in our understanding of relationships at work, this study briefly reviews the relevant literature on work relationships, extracting what is currently known about the specific aspects or underlying dimensions of such relationships. Then, the authors introduce an integrative multidimensional conceptualization of dyadic work relationships, which specifies the critical foundational dimensions and processes, and discusses the implications for future theory and research.
Immigrant Entrepreneurs, the Ethnic Enclave Strategy, and Venture Performance
Authors: Achidi Ndofor Hermann , Priem Richard L.
Published: October 2009

This study argues that first- and second-generation immigrant entrepreneurs’ endowments of economic, human, and social capital, together with their degrees of social identification with their ethnic community, affect their elemental strategic choice to pursue a venture strategy focused either on their ethnic enclave or the dominant market. The authors then propose that this choice affects venture performance indirectly, depending on how well the entrepreneur’s capital endowment allows the chosen strategy to be executed. The authors test these ideas via a field study of 103 first- and second-generation immigrant-owned ventures in a U.S. Midwest state. The findings indicate that immigrant entrepreneurs’ capital endowments and social identities influence their choice of an enclave versus dominant market venture strategy. Moreover, it is the particular alignment of entrepreneurial capital and strategy that ultimately shapes venture performance.
IPO Research in Management and Entrepreneurship: Moving the Agenda Forward
Authors: Certo S. Trevis , Holcomb Tim R. , Holmes R. Michael
Published: October 2009

Building on research from multiple fields, management and entrepreneurship scholars have shown increasing interest in the causes and consequences of initial public offerings (IPOs). The authors summarize this emerging literature and categorize research on IPOs into four broad themes: corporate governance, upper echelons, social influence, and innovation. They also review the various measures used by scholars to assess IPO performance. Based on this review, the authors develop an agenda for future research. This agenda provides both topics and research questions for future research and recommendations regarding IPO performance measurement.
Reason as danger and remedy for the modern subject in Hobbes’ Leviathan
Authors: Sadler Gregory B.
Published: October 2009

The article argues that Hobbes articulates a modern problematic of reason, where the shared rationality of human beings is an integral part of the danger they present to each other, and where reason suggests a solution, the social contract and the laws of nature, enforced and interpreted by absolute sovereign authority. This solution reflects a tension in modern reason itself, since it requires the alienation of self-determination of the rational human subject precisely to preserve the condition for the possibility of the rationality of the rational human subject, i.e. one’s life, which is threatened by the very rationality of other human subjects. I discuss interpretations of Hobbes which stress the other motives of conflict, i.e. competition and vanity, and acknowledge that they play a role in the threat subjects present to each other, but argue that the danger presented precisely by shared rationality, which I discuss with some reference to the Hegelian dialectic of consciousness and mutual recognition, has been underplayed by Hobbes’ interpretation.
Ethics versus morality
Authors: Harper Sarah J.
Published: October 2009

I explicate the distinction between ethics and morality in terms of four central contrasts, and argue (1) that moral theories that embrace the implicit divide are both theoretically and practically problematic in their failure to meet certain widely accepted standards of theoretical coherence and in their resulting propensity to generate indeterminable conflicts among norms, and (2) that social roles represent one aspect of the moral life that cannot be understood in terms of this distinction. My suggestion will be that we ought to explore an interpretation of the moral realm according to which all moral attributes are relative to social roles, since a role-centered morality promises a way of overcoming this problematic divide.
Prosecutorial Decision Making in Taiwan: A Partial Test of Black’s Behavior of Law
Authors: Kuo Shih-Ya , Longmire Dennis , Cuvelier Steven J. , Chang Kuang-Ming
Published: October 2009

Most prior studies have examined prosecutorial decision making from cognitive, organizational, and legal perspectives, with few studies applying a broad sociological model. This study attempts to address the gap by using Black’s Behavior of Law as a theoretical framework to explicate prosecutorial behavior. With analysis of aggregate-level data from Taiwan for the period 1973 to 2005, the results partially support Black’s propositions. Organization (martial law) and culture (educational attainment) are significantly associated with the levels of change in prosecutors’ behavior in the directions hypothesized using Black’s model. The remaining aspects of social life, however, do not have an effect on the prosecutors’ decisions during the time frame. The findings suggest that mediating variables, such as the extent of governmental autocracy and control over legislative policy, need to be considered in explaining the behavior of law.
The Efficacy of Vagus Nerve Stimulation in Intractable Epilepsy Associated With Nonketotic Hyperglycinemia in Two Children
Authors: Tsao Chang-Yong
Published: October 2009

Nonketotic hyperglycinemia is an inborn error of glycine metabolism and these patients frequently suffer from intractable epilepsy despite treatment with sodium benzoate, dextromethophan, and multiple anticonvulsants. We encountered 2 infants with nonketotic hyperglycinemia whose intractable generalized convulsive seizures were difficult to control with sodium benzoate, dextromethophan, and multiple anticonvulsants. However, after the addition of vagus nerve stimulation, their intractable generalized seizures were >75% reduced in frequency, the numbers of multiple anticonvulsants were reduced, and the quality of life significantly improved. The efficacy in seizure reduction persists for at least 3 years in both children.
Radiation Therapy for Pediatric Central Nervous System Tumors
Authors: Hoffman Karen E. , Yock Torunn I.
Published: October 2009

Radiation therapy is an important component of treatment of many pediatric central nervous system tumors. The radiation treatment target is determined by tumor histology, extent of disease, anticipated pattern of spread, and expected pattern of failure. Children cured of their tumors live to experience the long-term sequelae of radiation treatment, including developmental, neurocognitive, neuroendocrine, and hearing late effects. The development of more conformal radiation techniques has decreased inadvertent radiation dose to normal tissues and should decrease long-term treatment sequelae that are the result of normal tissue radiation. Intensity-modulated radiation therapy improves treatment conformity and decreases high dose to nearby normal tissues; however, it delivers a larger volume of low- and intermediate-dose radiation. Proton radiation eliminates exit dose to normal tissues, thereby eliminating approximately 50% of unnecessary radiation to normal tissues. The long-term clinical benefits of proton radiation in the pediatric population are just beginning to be reported in the literature.
Tour Guide Performance and Tourist Satisfaction: a Study of the Package Tours in Shanghai
Authors: Songshan Huang  , Hsu Cathy H. C. , Chan Andrew
Published: October 2009

This study examines tour guide performance and its relationship with tourist satisfaction in the context of package tours in Shanghai. A multilayer framework of tourist satisfaction in the package tour context is proposed. Tourist satisfaction was conceptualized to include three aspects/layers: satisfaction with guiding service, satisfaction with tour services, and satisfaction with the overall tour experience. Tour guide performance was found to have a significant direct effect on tourist satisfaction with guiding service and an indirect effect on satisfaction with tour services and with tour experience. Satisfaction with guiding service positively affected satisfaction with tour services but showed no direct effect on satisfaction with the overall tour experience. However, indirect effect of satisfaction with guiding service on satisfaction with tour experience mediated by satisfaction with tour services was significant. Implications for tour operators and government agencies are discussed.
Financial Impacts of Socially Responsible Activities on Airline Companies
Authors: Lee Seoki , Park Sun-Young
Published: October 2009

Although the concept of corporate social responsibility (CSR) has been recognized as an important ingredient for business success, the relationship between CSR and companies’ financial performance has been inconclusive and rarely examined in the airline industry. This study examines the impacts of CSR on airline companies’ financial performance in terms of accounting and value performance. In addition, the study investigates linear, quadratic, and cubic relationships between CSR and firm performance. Results show support for a positive and linear impact of CSR on value performance but not on accounting performance for airline companies. The findings can provide airline corporate executives with practical knowledge with which to strategically develop better business plans that incorporate CSR activities.
Consumer Goals and the Service Encounter: Evaluating Goal Importance and the Moderating Effect of Goal Progress on Satisfaction Formation
Authors: Noone Breffni M. , Mattila Anna S.
Published: October 2009

This study examines the stability of consumer goal importance across consumption episodes within the service encounter and the role of goal progress in the attribute— consumer satisfaction relationship in the context of restaurant experiences. Results indicate that consumers pursue multiple goals within the consumption experience, and the importance of those goals differs across consumption episodes within the experience. Using pace as a service attribute, it was found that goal progress moderates the impact of service attributes on consumer satisfaction. Satisfaction was high regardless of pace when goal progress was high. At low levels of goal progress, a moderate pace resulted in higher satisfaction than a slow or a fast pace. Implications for hospitality managers are discussed.
The efficacy and safety of enhanced external counterpulsation in patients with peripheral arterial disease
Authors: Thakkar Bhavik V , Hirsch Alan T , Satran Daniel , Bart Bradley A , Barsness Gregory , McCullough Peter A , Kennard Elizabeth D , Kelsey Sheryl F , Henry Timothy D
Published: October 2009

Peripheral arterial disease (PAD) is common in patients with severe coronary artery disease (CAD) and is considered a relative contraindication to external enhanced counterpulsation (EECP), but there are no data that define the efficacy and safety of EECP in patients with PAD. The International EECP Patient Registry (IEPR) was used to compare initial post-therapy and 2-year follow-up clinical outcomes and adverse event rates in patients with and without PAD. From January 2002 to October 2004, 2126 patients were enrolled in the IEPR, of whom 493 (23%) had a history of PAD. Immediately following EECP, the reduction in angina (≥ 1 Canadian Cardiovascular Society class) was similar in patients with and without PAD (76.6% vs 79.0%, p = 0.27) as was improvement in the Duke Activity Score Index (DASI) score (+4.7% vs +6.1%, p < 0.001). Both angina reduction and DASI score improvement were sustained at 2 years. PAD patients discontinued EECP more frequently (12.0% vs 8.5%, p < 0.05), but lower extremity ulceration did not occur more frequently in patients with PAD (3.7% vs 2.7%, p = 0.26). Rates of death (17.1% vs 8.6%, p < 0.001) and myocardial infarction (9.5% vs 5.0%, p < 0.001) were, as expected, higher in patients with PAD compared to patients without PAD at 2 years. In conclusion, while PAD patients constitute a high-risk cohort with known higher adverse event rates, EECP led to similar short- and long-term improvements in angina and quality of life for individuals with PAD compared to those without PAD.
Identities under construction: Women hailed as addicts
Authors: Aston Shaughney
Published: October 2009

Despite continuing investigations of the efficacy of Canadian addiction treatment services and supports across a range of health care settings and socio-cultural groups, many systemic, geographic and ideological barriers to service provision for women still exist. Determining how current services and supports can become more congruent with women’s gender-specific needs is a current research focus. Drawing on Butler’s reformulation of Althusser’s interpellation, this article explores the power of hailing, where hailing power lies, and how hailing operates in discourses about addiction that appear in women’s talk of their encounters with addiction services and supports. The article briefly outlines Butler’s understanding of interpellation and examines ways by which gender operates as both condition and effect in women becoming addicts. I argue that women’s narratives reveal patterns of interaction that intersect and generate complex social meanings and identities, and serve to get women’s attention in terms of seeing themselves as addicts. Further, I argue that powerful competing discourses concerning gender and the medicalization of addiction, hailed through these interactions, are taken up as lived realities by some women and resisted by others. Knowing how women are hailed to take up as their own, or resist, aspects of traditional and gendered discourses within addiction treatment and recovery communities can inform gender-compassionate service provision.
Pop goes the canon
Authors: Grixti Joe
Published: October 2009

This essay considers how contemporary perceptions of literary classics as exponents of cultural value have been modified by the commercial demands of contemporary popular media. Rather than eliminating traditional distinctions between high and low culture, the now habitual interactions and mutual borrowings between 'high' and 'pop' have given rise to significant changes in the discourse surrounding artistic value. Even as they appear to be evaporating or merging into each other, the old distinctions between 'low' and 'high' continue to pop up in dramatically different guises, repetitively reinscribing themselves in new forms of popular as well as educated artworks, but to new ends. The main focus of analysis are film and television adaptations of canonical literary texts, with particular emphasis on the types of choices made by screenwriters and producers when they adapt canonical works of literature with the aim of making them widely appealing to contemporary audiences.
Dermatomal Somatosensory Evoked Potentials and Electrical Perception Thresholds During Recovery From Cervical Spinal Cord Injury
Authors: Kramer John K. , Taylor Philippa , Steeves John D. , Curt Armin
Published: October 2009

Background. Dermatomal somatosensory evoked potentials (dSSEPs) not only provide a neurophysiological readout comparable with conventional SSEPs but also provide an opportunity to track changes in sensory function corresponding to individual dermatomes (ie, a single spinal segment) above, at, and below the level of spinal cord injury (SCI). Objectives. This study aimed to determine the reliability and responsiveness of dSSEPs and electrical perception thresholds (EPTs) to monitor changes in sensory function after cervical SCI. Methods. Initial and follow-up dSSEPs and EPTs were recorded from cervical dermatomes (C4-C8) of patients with traumatic tetraplegia (C3-C8; ASIA Impairment Scale A-D) during recovery after SCI (n = 18). Results. Follow-up examination of 74 initial dSSEPs unaffected by SCI (n = 18) revealed no significant change in latency (Δ = 0.0 ± 1.4 ms; P = .9) or EPT sensitivity (Δ = 0.1 ± 0.8 mA; P = .3). In 41 dSSEPs initially delayed after SCI (n = 14), latencies significantly decreased on follow-up examination (Δ = -3.1 ± 2.9 ms; P < .01) without a corresponding increase in sensitivity of the EPT (Δ = 0.2 ± 3.4 mA; P = .7). dSSEPs that were not measurable initially were subsequently recorded in 11 dermatomes (n = 5) on follow-up examination. This conversion of abolished-to-recordable dSSEPs was often preceded by the perception of an initial EPT and associated with a concomitant recovery of EPT at follow-up. Conclusion. dSSEPs and EPT can be reliably recorded to monitor changes in sensory function for each individual spinal segment after cervical SCI. dSSEPs may be potentially useful to monitor the safety of a therapeutic drug or cell transplant in early-phase (I/II) clinical trials as well as document the potential efficacy of interventions where the standard neurological assessment might not detect subtle therapeutic effects.
Repertoires of distinction
Authors: Measham Fiona , Moore Karenza
Published: October 2009

Presented here are the first findings of self report surveys of prevalence of illicit drug use by customers in the night time economy of a large English city. Five random sample surveys conducted with dance club customers and three similar surveys with bar customers identified an association between illicit drug use, entertainment type and venue type. First, club customers were significantly more likely to report lifetime, past month and fieldwork night drug use than bar customers. Second, distinct and prolific polydrug repertoires were associated with the genres of electronic dance music favoured within different clubs, along with evidence of the growing popularity of emergent drugs such as MDMA powder. Such polydrug repertoires support the notion of culturally, spatially and pharmacologically distinct local leisure scenes operating within the contemporary night time economy; rather than the same broad mass of customers choosing different leisure experiences on different occasions, or the more fluid, ‘neo-tribal’ cultural groupings suggested by some. The article concludes by suggesting that prolific and enduring weekend polydrug repertoires within local leisure scenes increasingly polarize such scenes from drug use in the general population, with implications for policing and governance, alongside the need for a more nuanced understanding of the night time economy as an analytical concept in social research.
Ball milling criteria for producing nano intermetallic compounds
Authors: Mirzadeh H. , Zomorodian A.
Published: October 2009

The effect of milling time and melting point of the powder materials on the evolution of grain size to the nanometre regime in intermetallic compounds was modelled and analysed by means of artificial neural network. The critical parameters of the milling process, namely, time to reach the 100 nm crystallite size, effective milling time, and crystallite size at this stage, were determined from this model. These criteria are important from the practical standpoint. Moreover, a relation between the effective crystallite size and the melting temperature of the compounds was established. The developed model is useful for design of experiments and process control for producing nanostructured intermetallics through ball milling and mechanical attrition processes.
Active screening at entry for tuberculosis among new immigrants: a systematic review and meta-analysis
Authors: Arshad S. , Bavan L. , Gajari K. , Paget S. N. J. , Baussano I.
Published: October 2009

Although there is no evidence that imported tuberculosis increases the incidence of the disease in host countries, the rise in migration worldwide raises concerns regarding the adequacy of surveillance and control of immigrant-associated tuberculosis in low incidence countries. Assessing the performance of screening of immigrants for tuberculosis is key to rationalising control policies for the detection and management of immigrant-associated tuberculosis.

We performed a systematic review and meta-analysis to determine the yield of active screening for tuberculosis among new immigrants at the point of entry.

The yield for pulmonary tuberculosis was 3.5 cases per 1,000 screened (95% CI 2.9–4.1; I2 = 94%); for refugees, asylum seekers and regular immigrants the estimates were 11.9 (95% CI 6.7–17.2; I2 = 92%), 2.8 (95% CI 2.0–3.7; I2 = 96%) and 2.7 (95% CI 2.0–3.4; I2 = 81%), respectively. The yield estimates for immigrants from Europe, Africa and Asia were 2.4 (95% CI 1.3–3.4; I2 = 51.5%), 6.5 (95% CI 3.2–10.0; I2 = 62%) and 11.2 (95% CI 6.2–16.1; I2 = 95%), respectively.

These results provide useful data to inform the development of coherent policies and rational screening services for the detection of immigrant-associated tuberculosis.
Dairy food, calcium and vitamin D intake in pregnancy, and wheeze and eczema in infants
Authors: Miyake Y. , Sasaki S. , Tanaka K. , Hirota Y.
Published: October 2009

The present prospective study examined the association between maternal consumption of dairy products, calcium, and vitamin D during pregnancy and the risk of wheeze and eczema in the infants aged 16–24 months.

Subjects were 763 Japanese mother–child pairs. Data on maternal intake during pregnancy were assessed with a diet history questionnaire. Symptoms of wheeze and eczema were based on criteria of the International Study of Asthma and Allergies in Childhood.

Higher maternal intake of total dairy products, milk, cheese and calcium during pregnancy was significantly related to a decreased risk of infantile wheeze, but not eczema (adjusted ORs (95% CI) between extreme quartiles were 0.45 (0.25−0.79), 0.50 (0.28−0.87), 0.51 (0.31−0.85), and 0.57 (0.32−0.99), respectively). When maternal vitamin D consumption during pregnancy was categorised into two groups using a cut-off point at the 25th percentile, children whose mothers had consumed ≥4.309 μg·day−1had a significantly reduced risk of wheeze and eczema (adjusted ORs (95% CI) were 0.64 (0.43−0.97) and 0.63 (0.41−0.98), respectively).

Higher consumption of calcium and dairy foods other than yoghurt during pregnancy may reduce the risk of infantile wheeze. Higher vitamin D intake during pregnancy may be protective against childhood wheeze and eczema.
Cigarette smoke modulates rhinovirus-induced airway epithelial cell chemokine production
Authors: Hudy M. H. , Traves S. L. , Wiehler S. , Proud D.
Published: October 2009

Human rhinovirus (HRV) infections induce epithelial cell production of chemokines that may contribute to the pathogenesis of exacerbations of chronic obstructive pulmonary disease (COPD) and asthma. Cigarette smoking is the predominant risk factor for the development of COPD and also aggravates asthma symptoms. We examined whether cigarette smoke extract (CSE) modulates viral inflammation by altering the profile of HRV-induced epithelial chemokine production.

Purified HRV-16, and CSE were used to examine the effects on CXC chemokine ligand (CXCL)8 and CXCL10 production from both primary human bronchial epithelial cells and the BEAS-2B epithelial cell line.

Both CSE and HRV-16 induced CXCL8 production and, when used in combination, induced at least an additive production of CXCL8 compared with either stimulus alone. In contrast, CSE did not induce CXCL10 and markedly inhibited HRV-16-induced CXCL10 production. Inhibition of HRV-16-induced CXCL10 by CSE was mediated, at least in part,viatranscriptional regulation. The increased CXCL8 production seen with the combination of CSE and HRV-16 was not due to transcriptional regulation but was associated with CXCL8 mRNA stabilisation.

Thus, CSE differentially modulates HRV-16-induced chemokine production from human airway epithelial cells in a manner that might be expected to alter inflammatory cell profiles.
TIde: a software for the systematic scanning of drug targets in kinetic network models
Authors: Schulz Marvin , Bakker Barbara M , Klipp Edda
Published: October 2009

Background

During the stages of the development of a potent drug candidate compounds can fail for several reasons. One of them, the efficacy of a candidate, can be estimated in silico if an appropriate ordinary differential equation model of the affected pathway is available. With such a model at hand it is also possible to detect reactions having a large effect on a certain variable such as a substance concentration.

Results

We show an algorithm that systematically tests the influence of activators and inhibitors of different type and strength acting at different positions in the network. The effect on a quantity to be selected (e.g. a steady state flux or concentration) is calculated. Moreover, combinations of two inhibitors or one inhibitor and one activator targeting different network positions are analysed. Furthermore, we present TIde (Target Identification), an open source, platform independent tool to investigate ordinary differential equation models in the common systems biology markup language format. It automatically assigns the respectively altered kinetics to the inhibited or activated reactions, performs the necessary calculations, and provides a graphical output of the analysis results. For illustration, TIde is used to detect optimal inhibitor positions in simple branched networks, a signalling pathway, and a well studied model of glycolysis in Trypanosoma brucei.

Conclusion

Using TIde, we show in the branched models under which conditions inhibitions in a certain pathway can affect a molecule concentrations in a different. In the signalling pathway we illuminate which inhibitions have an effect on the signalling characteristics of the last active kinase. Finally, we compare our set of best targets in the glycolysis model with a similar analysis showing the applicability of our tool.
Ras promotes cell survival by antagonizing both JNK and Hid signals in the Drosophilaeye
Authors: Wu Yue , Zhuang Yuan , Han Min , Xu Tian , Deng Kejing
Published: October 2009

Background

Programmed cell death, or apoptosis, is a fundamental physiological process during normal development or in pathological conditions. The activation of apoptosis can be elicited by numerous signalling pathways. Ras is known to mediate anti-apoptotic signals by inhibiting Hid activity in the Drosophila eye. Here we report the isolation of a new loss-of-function ras allele, ras

KP
, which causes excessive apoptosis in the Drosophila eye.

Results

This new function is likely to be mediated through the JNK pathway since the inhibition of JNK signalling can significantly suppress ras

KP
-induced apoptosis, whereas the removal of hid only weakly suppresses the phenotype. Furthermore, the reduction of JNK signalling together with the expression of the baculovirus caspase inhibitor p35, which blocks Hid activity, strongly suppresses the ras

KP
cell death. In addition, we find a strong correlation between ras

KP
-induced apoptosis in the eye disc and the activation of JNK signalling.

Conclusion

In the Drosophila eye, Ras may protect cells from apoptosis by inhibiting both JNK and Hid activities. Surprisingly, reducing Ras activity in the wing, however, does not cause apoptosis but rather affects cell and organ size. Thus, in addition to its requirement for cell viability, Ras appears to mediate different biological roles depending on the developmental context and on the level of its expression.
Widespread variation in transcript abundance within and across developmental stages of Trypanosoma brucei
Authors: Jensen Bryan C , Sivam Dhileep , Kifer Charles T , Myler Peter J , Parsons Marilyn
Published: October 2009

Background

Trypanosoma brucei, the causative agent of African sleeping sickness, undergoes a complex developmental cycle that takes place in mammalian and insect hosts and is accompanied by changes in metabolism and cellular morphology. While differences in mRNA expression have been described for many genes, genome-wide expression analyses have been largely lacking. Trypanosomatids represent a unique case in eukaryotes in that they transcribe protein-coding genes as large polycistronic units, and rarely regulate gene expression at the level of transcription initiation.

Results

Here we present a comprehensive analysis of mRNA expression in several stages of parasite development. Utilizing microarrays that have multiple copies of multiple probes for each gene, we were able to demonstrate with a high degree of statistical confidence that approximately one-fourth of genes show differences in mRNA expression levels in the stages examined. These include complex patterns of gene expression within gene families, including the large family of variant surface glycoproteins (VSGs) and their relatives, where we have identified a number of constitutively expressed family members. Furthermore, we were able to assess the relative abundance of all transcripts in each stage, identifying the genes that are either weakly or highly expressed. Very few genes show no evidence of expression.

Conclusion

Despite the lack of gene regulation at the level of transcription initiation, our results reveal extensive regulation of mRNA abundance associated with different life cycle and growth stages. In addition, analysis of variant surface glycoprotein gene expression reveals a more complex picture than previously thought. These data provide a valuable resource to the community of researchers studying this lethal agent.
Regulation of phenylacetic acid degradation genes of Burkholderia cenocepacia K56-2
Authors: Hamlin Jason NR , Bloodworth Ruhi AM , Cardona Silvia T
Published: October 2009

Background

Metabolically versatile soil bacteria Burkholderia cepacia complex (Bcc) have emerged as opportunistic pathogens, especially of cystic fibrosis (CF). Previously, we initiated the characterization of the phenylacetic acid (PA) degradation pathway in B. cenocepacia, a member of the Bcc, and demonstrated the necessity of a functional PA catabolic pathway for full virulence in Caenorhabditis elegans. In this study, we aimed to characterize regulatory elements and nutritional requirements that control the PA catabolic genes in B. cenocepacia K56-2.

Results

Translational fusions of the PA degradation gene promoters with eGFP were constructed and introduced in B. cenocepacia K56-2. eGFP expression was observed when the reporter strains were grown in minimal media containing glycerol and PA or other compounds expected to proceed through the PA pathway, and in synthetic CF medium (SCFM). Addition of succinate or glucose to the PA containing medium repressed eGFP expression. To show that BCAL0210, a putative TetR-type regulator gene encodes a regulator for the PA genes in B. cenocepacia, we developed a BCAL0210 insertional mutant reporter strain. Results show that these strains exhibit fluorescence regardless of the presence of PA in the culture.

Conclusion

The PA catabolic genes of B. cenocepacia K56-2 are induced by PA and other related compounds, are negatively regulated by PaaR (named herein), a TetR-type regulator, and are subjected to catabolic repression by glucose and succinate. As the PA catabolic pathway of B. cenocepacia appears to be induced during growth in synthetic cystic fibrosis medium (SCFM), further research is necessary to determine the relevance of this pathway in CF-like conditions and in other host-pathogen interactions.