bluuebunny/crossref_metadata_2025 huggingface dataset:
Counterproductive Work Behavior and Organisational Citizenship Behavior: Are They Opposite Forms of Active Behavior?
Authors: Spector Paul E. , Fox Suzy
Published: December 2009

We question the common supposition that active acts of counterproductive work behavior (CWB) and organisational citizenship behavior (OCB) are negatively related in that people who perform one tend not to perform the other, and that they tend to relate oppositely to potential antecedents. We argue that under some circumstances these active behaviors may occur together or sequentially. Using an emotion focused framework, we discuss five situations that lead from one form of behavior to the other: Understimulation at work, co‐worker lack of performance, organisational constraints, lack of expected rewards for OCB, and unjustified (to the actor) acts of CWB. Finally, we provide suggestions for studying these behaviors episodically as opposed to aggregating frequencies of behavior over extended periods of time.

Nous mettons en doute l'idée commune selon laquelle les actions relevant d'un comportement professionnel contre‐productif (CWB) et les conduites citoyennes dans l'organisation (OCB) sont négativement corrélées en ce sens que les individus qui adopteraient les unes auraient tendance à se détourner des autres et qu'elles seraient liées en sens contraire aux antécédents potentiels. Nous pensons que dans certains cas ces comportements actifs peuvent émerger conjointement ou à la suite les uns des autres. A partir d'un schéma centré sur l'émotion, nous analysons cinq situations qui orientent d'une forme de comportement vers l'autre: le manque de stimulants au travail, les médiocres performances d'un collègue, les contraintes organisationnelles, l'absence des gratifications attendues pour l'OCB et des actions de CWB injustifiées (contre l'acteur). Nous proposons enfin d'étudier ces conduites sur des laps de temps définis plutôt que d'additionner des occurrences de comportement sur de longues périodes.
The Role of Resource Flexibility in Leveraging Strategic Resources
Authors: Combs James G. , Ketchen, Jr David J. , Ireland R. Duane , Webb Justin W.
Published: December 2009

abstract

Recent advances in resource‐based theory suggest that the ways managers use strategic actions to leverage resources has important influences on firms' resulting competitive advantages. However, theory dealing with the nature of leveraging remains underdeveloped. We develop the notion that strategic actions that successfully leverage one resource might not leverage another resource. In particular, our theorizing distinguishes between flexible resources that can be leveraged in new markets and rigid resources that must be leveraged in their current market. Using data from the restaurant industry, we find evidence that top management team experience (a flexible resource) can be profitably leveraged by franchising, but that attempting to leverage specific knowledge (a rigid resource) through either franchising or multi‐chaining weakens performance. Our theory and results help explain how different types of resources can be leveraged using different strategic actions.
Path Dependence or Path Creation?
Authors: Garud Raghu , Kumaraswamy Arun , Karnøe Peter
Published: December 2009

abstract

We discuss the assumptions that underlie path dependence, as defined by Vergne and Durand, and then provide the outlines of an alternative perspective which we label as path creation. Path creation entertains a notion of agency that is distributed and emergent through relational processes that constitute phenomena. Viewed from this perspective, ‘initial conditions’ are not given, ‘contingencies’ are emergent contexts for action, ‘self‐reinforcing mechanisms’ are strategically manipulated, and ‘lock‐in’ is but a temporary stabilization of paths in‐the‐making. We develop these points using a narrative approach and highlight the theoretical and methodological implications of our perspective.
The Australian Citizenship Test: Process and Rhetoric
Authors: Fozdar Farida , Spittles Brian
Published: December 2009

In late 2007, Australia's relatively liberal citizenship eligibility requirements were modified, ostensibly to improve the value of citizenship by restricting access to it. A key change involved the introduction of a citizenship test. This article tracks its development and implementation. We challenge claims of overwhelming support for the test, explore the discourses around the “Australian values” being tested, and outline the process by which the legislation was enacted (during which a number of principles of parliamentary democracy were compromised). Using evidence from politicians' speeches, we argue the citizenship test served to re‐direct the Australian imagination away from a nascent “multicultural” identity, back to one redolent of the times of the “White Australia Policy”, confidently celebrating connections with an Anglo‐Saxon heritage, the European Enlightenment, and Judeo‐Christian roots. As such it was a key aspect of the 1996–2007 Howard Government's retreat from multiculturalism.
From the Gallery to the Parliament: Journalists in the House of Representatives and Senate, 1901–2007
Authors: Errington Wayne , Miragliotta Narelle
Published: December 2009

In this article we examine the extent of career cross‐over from journalism to politics in Australia using biographical data on the pre‐parliamentary careers of federal politicians since 1901. We find that while journalists continue to be over‐represented in Australia's national Parliament, there is evidence of a decline in the number making the career switch to politics. We argue that one explanation for this is the growing professionalisation of both vocations, and of journalism especially. Journalism education inculcates in graduates a strong sense of the media's Fourth Estate role, contributing to a professional identity that militates against taking up a political career. We also find that in recent decades, in spite of a small number of celebrated cases of journalists joining the ranks of the ALP, prior careers in journalism have been more prevalent among Coalition MPs. We argue that this reflects an ALP pre‐selection system that has become less accommodating of all pre‐parliamentary occupations other than trade union official and political staffer.
Regulating Rule‐Making via Impact Assessment
Authors: RADAELLI CLAUDIO M.
Published: December 2009

In their attempt to promote “better regulation,” governments have ended up with increasing regulation of rule‐making. Regulatory impact assessment (RIA) is a manifestation of this trend. This article draws on the positive political economy hypothesis that RIA is an administrative control device. Rational politicians—positive political economy argues—design administrative requirements to solve problems of political uncertainty. This is a rather abstract hypothesis but with clearly observable implications. Empirical analysis on Canada, Denmark, the Netherlands, Sweden, the United Kingdom, the United States, and the EU shows that the modes and level of control vary, with almost no evidence supporting the positive political economy hypothesis in Denmark and Sweden and more robust evidence in the other cases, especially the United States and the United Kingdom. The EU scores high, but control has both a political component and an infra‐organizational dimension. In between the extremes I find modest levels of political control in Canada and the Netherlands.
Contemporary Discourses and Contestations around Pro‐Poor Land Policies and Land Governance
Authors: BORRAS JR SATURNINO M. , FRANCO JENNIFER C.
Published: December 2009

The meaning of land and land policies is diverse and contested across and within local and (inter)national settings. The phrase ‘land policy’, used to refer to all policies that have anything to do with land, may be convenient, but it masks the actual complexity of issues. Meanwhile, concern for ‘pro‐poor’ land policy has coincided with the mainstream promotion of efficient administration of land policies, leading to the concept of ‘land governance’. Such concepts have enriched discussion on land issues, but they also complicate further an already complex terrain. In response, this paper offers possible analytical signposts, rather than an actual in‐depth and elaborated analytical exploration of this terrain. It hopes to be a modest step forward and towards a better understanding of contemporary policy discourses and political contestations around land and land governance.
Co‐operativity in agonist binding at the D2dopamine receptor: evidence from agonist dissociation kinetics
Authors: Kara Elodie , Lin Hong , Strange Philip G.
Published: December 2009

J. Neurochem.(2010)112, 1442–1453.

There is much evidence to suggest that G protein coupled receptors exist as oligomers but the relevance to their function is unclear. We have, therefore, examined the binding of the radiolabelled agonist [3H]NPA to membranes of CHO cells expressing the D2dopamine receptor in dissociation rate experiments. When [3H]NPA dissociation was started by dilution, the dissociation rate in the absence of sodium ions was unaffected by addition of the antagonist/inverse agonist (+)‐butaclamol, but was accelerated by addition of agonists e.g. dopamine, suggesting that the receptor was not behaving as a monomer with a single binding site. The very low efficacy partial agonist, aripiprazole provided an intermediate level of acceleration of dissociation. [3H]NPA dissociation experiments started by addition of ligands without dilution gave a similar pattern. [3H]NPA dissociation could also be accelerated by GTP. Dissociation of [3H]NPA in the presence of GTP and dopamine provided a greater acceleration than for either modulator alone, suggesting synergistic effects related to receptor/G protein interaction. When [3H]NPA dissociation experiments were performed in the presence of sodium ions, dissociation was faster than in their absence but the rate still depended on the ligand present in the assay. Overall the data cannot be explained by a ternary complex model and are consistent with an oligomeric receptor in which binding of [3H]NPA, as an example of an agonist ligand, can be modulated co‐operatively by ligands binding elsewhere in the oligomer. Interactions with G proteins also occurs providing further modulation of [3H]NPA binding. Both agonists and G proteins are proposed to modulate the oligomer by switching high affinity agonist binding sites to low affinity sites.
Evaluating the Distributional Implications of Price Movements: Methodology, Application and Australian Evidence*
Authors: NICHOLAS AARON , RAY RANJAN , VALENZUELA MA. REBECCA
Published: December 2009

This article investigates the distributional implication of relative price movements in Australia. It proposes and applies a method of evaluating the nature and size of the inequality bias of price movements. In the process, the study introduces a new demographic demand model that yields sensible and statistically significant estimates of the general equivalence scale and the size economies of scale. The study finds that relative price movements in Australia during the 1990s had an inequality increasing bias and that this bias increased in the late 1990s and the first part of the new millennium. The disaggregated analysis of the inequality movements shows that the regressive nature of relative price changes affected the renters much more than non‐renters. The study also provides evidence on the decomposition of overall inequality between demographic groups and compares the decomposition between the nominal and real expenditure inequalities.
Quercetin and its major metabolites selectively modulate cyclic GMP‐dependent relaxations and associated tolerance in pig isolated coronary artery
Authors: Suri S , Liu XH , Rayment S , Hughes DA , Kroon PA , Needs PW , Taylor MA , Tribolo S , Wilson VG
Published: December 2009

Background and purpose: Quercetin is a major flavonoid that contributes to the reduced risk of cardiovascular disease associated with dietary ingestion of fruits and vegetables. We have pharmacologically characterized the effect of quercetin, and its sulphate and glucuronide metabolites, on vasoconstrictor and vasodilator responses in the porcine isolated coronary artery.

Experimental approach: Segments of the porcine coronary artery were prepared for either isometric tension recording or determination of cyclic GMP content. The effect of quercetin and metabolites on submaximal responses to U46619 was examined in the presence and absence of substance P, bradykinin, forskolin, sodium nitroprusside (SNP) and glyceryl trinitrate (GTN).

Key results: Quercetin and quercetin 3′‐sulphate inhibited endothelin and U46619‐induced contractions with greater potency (three‐ to fivefold) against the former, while quercetin 3‐glucoronide was inactive. Quercetin enhanced both the cyclic GMP content of the artery (threefold) and cyclic GMP‐dependent relaxations to GTN and SNP (two to threefold), but forskolin‐induced relaxations were unaffected. Although the effect of quercetin was qualitatively similar to that noted for UK‐114,542, a selective inhibitor of phosphodiesterase 5, it was still evident against SNP‐induced relaxations in the presence of 10 nM UK‐114,542. Quercetin and quercetin 3′‐sulphate significantly reduced the development of GTN‐associated ‘tolerance’.

Conclusions and implications: Quercetin and quercetin 3′‐sulphate inhibited receptor‐mediated contractions of the porcine isolated coronary artery by an endothelium‐independent action. Quercetin selectively enhanced cyclic‐GMP‐dependent relaxations by a mechanism not involving phosphodiesterase 5 inhibition. In addition, quercetin and quercetin 3′‐sulphate opposed GTN‐induced tolerancein vitro, which may be beneficial for patients treated for angina pectoris.
Stimulation of adenosine A2Breceptors induces interleukin‐6 secretion in cardiac fibroblasts via the PKC‐δ–P38 signalling pathway
Authors: Feng Wei , Song Yao , Chen Chao , Lu Zhi Zhen , Zhang Youyi
Published: December 2009

Background and purpose: Inflammatory response and cytokine activation are markedly stimulated after myocardial infarction, and contribute to cardiac remodelling. Interleukin‐6 (IL‐6), a pro‐inflammatory cytokine, has pleiotropic effects on cardiac remodelling. Adenosine, released by all cell types, binds to a class of G protein‐coupled receptors to induce various cardiovascular effects. The aim of this work was to investigate whether activation of adenosine receptors, particularly A2Badenosine receptors, could stimulate IL‐6 secretion in cardiac fibroblasts (CFs).

Experimental approach: elisawas used to assess IL‐6 concentration in supernatant, and immunostaining was used to analyse IL‐6 protein level in CFs. The levels of phosphorylated and total p38, extracellular signal‐regulated kinase, c‐Jun N‐terminal kinase and protein kinase C‐δ (PKC‐δ) were determined by Western blot analysis.

Key results: Adenosine‐5′‐N‐ethyluronamide (NECA), a stable adenosine analogue, dose‐ and time‐dependently stimulated IL‐6 secretion in CFs. The effect of NECA was dose‐dependently inhibited by an A2Bantagonist, and silencing of the A2Breceptor also inhibited IL‐6 secretion. By using PKC isoform‐selective inhibitors and translocation peptide inhibitors, the PKC‐δ isoform was found to be involved in the up‐regulation of IL‐6 production. Inhibition of p38 by SB203580, and adenoviral transfer of dominant‐negative p38 inhibited NECA‐induced IL‐6 production. Furthermore, PKC‐δ functioned as an upstream regulator of p38 MAPK in this process.

Conclusions and implications: We demonstrated a novel relationship between adenosine and IL‐6 secretion, in that IL‐6 secretion induced by NECA was mediated by adenosine A2Breceptor activation in CFs and was dependent on a PKCδ–P38 pathway.

This article is commented on by Cohenet al., pp. 1595–1597 of this issue. To view this commentary visithttp://dx.doi.org/10.1111/j.1476‐5381.2010.00668.x
Strategic Human Resource Practices: Introducing Alternatives for Organizational Performance Improvement in the Public Sector
Authors: Kim Jungin
Published: December 2009

Can public sector organizations increase productivity through competition in spite of inherent limitations, such as budget constraints? This study addresses that question by examining the impact of four factors that contribute to employees’ expectations regarding competitive work environments on organizational performance in terms of overall quality of work and client satisfaction. The four factors measured include rewards for merit such as salary and benefits, opportunities, organizational rules, and the capacity to deal with risks as perceived by employees. Using data on public and nonprofit sector employees, expectations for merit rewards were positively related to employees’ perception of organizational performance when the conditions of performance‐based organizational rules and risk‐taking behaviors were also satisfied. Moreover, employees’ perceptions of organizational performance tended to increase when they felt that organizational rules were oriented toward performance plus organizational members and top leaders exhibited greater risk‐taking behaviors. However, no correlation was evident between employees’ expectations of opportunities and perceived organizational performance.
Using Protistan Examples to Dispel the Myths of Intelligent Design
Authors: FARMER MARK A. , HABURA ANDREA
Published: December 2009

ABSTRACT. In recent years the teaching of the religiously based philosophy of intelligent design (ID) has been proposed as an alternative to modern evolutionary theory. Advocates of ID are largely motivated by their opposition to naturalistic explanations of biological diversity, in accordance with their goal of challenging the philosophy of scientific materialism. Intelligent design has been embraced by a wide variety of creationists who promote highly questionable claims that purport to show the inadequacy of evolutionary theory, which they consider to be a threat to a theistic worldview. We find that examples from protistan biology are well suited for providing evidence of many key evolutionary concepts, and have often been misrepresented or roundly ignored by ID advocates. These include examples of adaptations and radiations that are said to be statistically impossible, as well as examples of speciation both in the laboratory and as documented in the fossil record. Because many biologists may not be familiar with the richness of the protist evolution dataset or with ID‐based criticisms of evolution, we provide examples of current ID arguments and specific protistan counter‐examples.
An Examination of the Effects of Teacher Intervention During Sensory Play on the Emotional Development of Preschoolers
Authors: Maynard Christine N. , Adams Rebecca A. , Lazo‐Flores Thelma , Warnock Kresha
Published: December 2009

Implementing specific interventions during sensory play time to stimulate the emotional development of preschoolers’ at a Midwestern university Child Study Center was investigated. The constructs studied were (i) children’s ability to label the emotions expressed by other children, (ii) their ability to self‐regulate or control their impulses, and (iii) the frequency of their aggressive acts. A new instrument, the Expressed Emotion Identification Tool, which measures children’s ability to label the emotions of others and uses only pictorial stimuli is described. Measurement of changes in preschoolers’ self‐controlling behaviors, aggressiveness, and nonaggressive problem solving showed no statistically significant differences between experimental and control groups. Anecdotal data, however, show positive outcomes and indicate a need for further study to determine the benefits of using interventions during sensory play to aid in preschoolers’ emotional development.
How Leadership Opportunities in Family and Consumer Sciences Shaped the Accomplishments of Ann Collins Chadwick
Authors: Vincenti Virginia B. , Bardon Carol A.
Published: December 2009

The research in this article reflects upon the legacy of a Family and Consumer Sciences leader, Ann Collins Chadwick. It is also intended to fill in a gap in the history of the profession through the experiences of a professional in the field. Research for this article was accomplished through a recorded interview, e‐mail correspondence, her personal papers, and Internet research. Ann’s early years were spent living a simple life on a small dairy farm in Mississippi. In her thirties, when she was attending college, she began a dramatic transformation. She demonstrated her professional competence in her nutritional and consumer affairs work in the food industry and in the U.S. Department of Agriculture. Her administrative ability and commitment to the profession further developed during her tenure as Executive Director of the American Association of Family and Consumer Sciences. She has served as a board member of Friends of the World Food Programme, and has been professionally active into her retirement years. Ann has been a leader, administrator, mentor, colleague, and friend to many.
Issue Streams and Open Solutions: A New Approach to Family‐Home Decisions
Authors: Kleppe Ingeborg Astrid , Grønhaug Kjell
Published: December 2009

This article takes a new perspective on family‐home decisions as an issue evolving over time and in the context of other family decisions. An intriguing discovery is that the first family home is important as a negotiation site for the development of preferences for future homes. Due to loss of buyer power in the decision preceding first high‐commitment family home financial overcommitment and extensive renovation projects are common. Moreover, family home is a constantly recurring consumption issue. When faced with multiple concurrent decision issues, a family may choose temporary open solutions with substantial trade‐offs when ideal solutions are not feasible.
An Ecological Approach to Examining Body Satisfaction in Caucasian and African American Female College Students
Authors: Sira Natalia , Ballard Sharon M.
Published: December 2009

Body satisfaction is a multifaceted concept that depends upon inner biological, psychological, social, and cultural components. Although research has demonstrated the influence of culture and family on the etiology of eating disorders, few studies have examined how these variables are associated with body satisfaction in a nonclinical, racially diverse college population. This study explores the mediating role of race in the assessment of family environment, associated with body satisfaction in college females. More specifically, body mass index (BMI), self‐worth, eating behavior, parental attachment, parental control, and media influence are examined in relation to perceived body satisfaction. Females in a southeastern university (231 Caucasians, 80 African Americans) aged 18–24, completed two subscales of Harter’s Self‐Perception Scale for College Students assessing self‐worth and body satisfaction. Participants reported height and weight to calculate BMI and completed an eating behavior (EAT‐26) scale. Attachment to both parents was measured by the Inventory of Parent and Peer Attachment. Perception of media was assessed by the Media Influence Scale, developed specifically for this study. For both groups, BMI was a predictor of body satisfaction. Self‐worth, parental attitudes, media influence, and eating behaviors demonstrated unique interplay with regard to perceived body satisfaction for each race. Findings indicate that body satisfaction, an essential part of self‐worth, is constructed differently by each race, and associated with familial variables in distinctive ways.
Effects of combined endurance and strength training on muscle strength, power and hypertrophy in 40–67‐year‐old men
Authors: Karavirta L. , Häkkinen A. , Sillanpää E. , García‐López D. , Kauhanen A. , Haapasaari A. , Alen M. , Pakarinen A. , Kraemer W. J. , Izquierdo M. , Gorostiaga E. , Häkkinen K.
Published: December 2009

Both strength and endurance training have several positive effects on aging muscle and physical performance of middle‐aged and older adults, but their combination may compromise optimal adaptation. This study examined the possible interference of combined strength and endurance training on neuromuscular performance and skeletal muscle hypertrophy in previously untrained 40–67‐year‐old men. Maximal strength and muscle activation in the upper and lower extremities, maximal concentric power, aerobic capacity and muscle fiber size and distribution in the vastus lateralis muscle were measured before and after a 21‐week training period. Ninety‐six men [mean age 56 (SD 7) years] completed high‐intensity strength training (S) twice a week, endurance training (E) twice a week, combined training (SE) four times per week or served as controls (C). SE and S led to similar gains in one repetition maximum strength of the lower extremities [22 (9)% and 21 (8)%, P<0.001], whereas E and C showed minor changes. Cross‐sectional area of type II muscle fibers only increased in S [26 (22)%, P=0.002], while SE showed an inconsistent, non‐significant change [8 (35)%, P=0.73]. Combined training may interfere with muscle hypertrophy in aging men, despite similar gains in maximal strength between the strength and the combined training groups.
A clinical investigation into the microbiological status of ‘locally infected’ leg ulcers
Authors: Cooper Rose A , Ameen Hanar , Price Patricia , McCulloch Dorothy A , Harding Keith G
Published: December 2009

Cooper RA, Ameen H, Price P, McCulloch DA, Harding KG. A clinical investigation into the microbiological status of ‘locally infected’ leg ulcers

The complex interactions between patients and the microbial species that reside in their wounds are not yet fully characterised. Investigations to date have dealt with either those organisms that cause infections or those that establish long‐term colonisations. The objective of this open, prospective pilot study was to quantitatively and qualitatively assess the microbiological status of ‘locally infected’ venous leg ulcers. Three different sampling techniques were used to recover organisms from 20 venous leg ulcers that had failed to progress towards healing and comparisons made to explore the distribution of colonised flora within the wound. In total, 116 isolates were recovered (mean of 5·8 per ulcer) with highest recovery rates seen with swabs. Greatest agreement of colonisation and counts was found between swabs and absorbent polyvinyl acetate (PVA) foam disc, and also between PVA discs and biopsies. Lowest agreement was between the distribution of anaerobes and coryneforms in swabs and biopsies, suggesting uneven vertical distribution within ulcers. No justification for using routine biopsies in locally infected venous leg ulcers was found.
What to do about banks
Authors: Lapavitsas Costas
Published: December 2009

Costas Lapavitsas considers the political economy of bloated finance and makes a case for establishing democratically‐run public banks, which, he asserts, could strengthen the social and the collective in modern economies
From the Olympics to the grassroots: What will London 2012 mean for sport funding and participation in Britain?
Authors: Kavetsos Georgios , Szymanski Stefan
Published: December 2009

Georgios Kavetsos and Stefan Szymanski show that while sports facilities managers are mainly optimistic about the benefits of the Olympics for encouraging sports participation generally, there are some concerns about the impacts locally
Peritonitis Associated With Pasteurella multocida: Molecular Evidence of Zoonotic Etiology
Authors: Satomura Atsushi , Yanai Mitsuru , Fujita Takayuki , Arashima Yasutomo , Kumasaka Kazunari , Nakane Chie , Ito Ken , Fuke Yoshinobu , Maruyama Takashi , Maruyama Noriaki , Okada Kazuyoshi , Nakayama Tomohiro , Matsumoto Koichi
Published: December 2009

A patient on continuous cyclic peritoneal dialysis for chronic kidney disease due to type 2 diabetes mellitus developed peritoneal dialysis‐associated peritonitis induced by Pasteurella multocida that was isolated from a sample of dialysis effluent. The route of infection was unknown for this case; however, P. multocida was also isolated from a culture of a pharyngeal swab obtained from the patient's cat. There was no evidence that the cat had bitten and ruptured the peritoneal dialysis tubing or bags. Pulsed‐field gel electrophoresis (PFGE) showed that the P. multocida isolated from the patient was completely identical to the strain isolated from the domestic cat. As there is a rise in the pet‐keeping population, an increase in zoonoses is to be expected. It is necessary to be carefully informed of hygiene rules in keeping pets because a pet may transmit zoonoses, even on casual contact.
Diffractive microlensing – I. Flickering planetesimals at the edge of the Solar system
Authors: Heyl Jeremy
Published: December 2009

Microlensing and occultation are generally studied in the geometric optics limit. However, diffraction may be important when recently discovered Kuiper Belt objects (KBOs) occult distant stars. In particular, the effects of diffraction become more important as the wavelength of the observation and the distance to the KBO increase. For sufficiently distant and massive KBOs or Oort cloud objects not only is diffraction important but so is gravitational lensing. For an object similar to Eris but located in the Oort cloud, the signature of gravitational lensing would be detected easily during an occultation and would give constraints on the mass and radius of the object.
N‐Methylated Cyclic Enkephalin Analogues Retain High Opioid Receptor Binding Affinity
Authors: Weltrowska Grazyna , Berezowska Irena , Lemieux Carole , Chung Nga N. , Wilkes Brian C. , Schiller Peter W.
Published: December 2009

In an effort to improve the bioavailability of the non‐selective, cyclic enkephalin analogues H‐Dmt‐c[d‐Cys‐Gly‐Phe‐d(or L)‐Cys]NH2 (Dmt = 2′,6′‐dimethyltyrosine), analogues N‐methylated at the Phe4 and/or Cys5 residue were synthesized. In comparison with the non‐methylated parent peptides, all mono‐ and N‐di‐methylated analogues in general retained high binding affinities at all three opioid receptors and high opioid agonist potencies in functional opioid activity assays. The results indicate that the progressive conformational restriction in these compounds upon mono‐ and di‐N‐methylation did not significantly affect the in vitro opioid activity profile. A low‐energy conformer identified for the conformationally most restricted analogue of the series, H‐Dmt‐c[D‐Cys‐Gly‐Phe(NMe)‐L‐Cys(NMe)]NH2 (6), showed good spatial overlap of the essential pharmacophoric moieties with those in the proposed μ receptor‐bound conformation of the μ‐selective opioid peptide JOM‐6 [H‐Tyr‐c(S‐Et‐S)[D‐Cys‐Phe‐D‐Pen]NH2] (Pen = penicillamine) [Mosberg M.I. and Fowler C.B. (2002) J Peptide Res; 60:329–335], in agreement with the moderate μ selectivity determined for this compound. An analogue of 6 containing (2S)‐2‐methyl‐3‐(2,6‐dimethyl‐4‐hydroxyphenyl)propanoic acid [(2S)‐Mdp] in place of Dmt1 was an opioid antagonist with quite high opioid receptor binding affinities and can be expected to show improved bioavailability because of its further increased lipophilicity and reduced hydrogen‐bonding capacity.
Evaluating Oversight of Human Drugs and Medical Devices: A Case Study of the FDA and Implications for Nanobiotechnology
Authors: Paradise Jordan , Tisdale Alison W. , Hall Ralph F. , Kokkoli Efrosini
Published: December 2009

This article evaluates the oversight of drugs and medical devices by the U.S. Food and Drug Administration (FDA) using an integration of public policy, law, and bioethics approaches and employing multiple assessment criteria, including economic, social, safety, and technological. Throughout, assessments employing both the multiple criteria and a method of expert elicitation are combined with the existing literature, case law, and regulations providing an integrative historical case study approach. The goal is to provide useful information from multiple disciplines and perspectives to guide discussions regarding appropriate oversight frameworks for nanobiotechnology applications under the FDA’s purview.
Governance of Nanotechnology and Nanomaterials: Principles, Regulation, and Renegotiating the Social Contract
Authors: Kimbrell George A.
Published: December 2009

How should we oversee new and emerging technologies and their products? What lessons can we discern from existing regulatory examples and from past mistakes? How do these lessons learned translate into informed recommendations for adequate oversight for nanotechnology to avoid repeating the mistakes of the past? The investigators of this interdisciplinary project undertook this endeavor intending to answer these questions among others.

In parallel with the project team putting together this symposium, another, very different process on the oversight of nanotechnology took place. An international coalition of non-governmental organizations (NGOs) formed to address the nanotech policy dialogue. The first goal of this NGO group was to agree upon and draft fundamental principles of oversight, which it completed in 2007-08. These principles close with a call for their adoption and/or internalization by all relevant actors and bodies. In effect, they serve a function in the policy dialogue similar to that of this project’s forthcoming recommendations.
Problem Formulation and Option Assessment (PFOA) Linking Governance and Environmental Risk Assessment for Technologies: A Methodology for Problem Analysis of Nanotechnologies and Genetically Engineered Organisms
Authors: Nelson Kristen C. , Andow David A. , Banker Michael J.
Published: December 2009

Societal evaluation of new technologies, specifically nanotechnology and genetically engineered organisms (GEOs), challenges current practices of governance and science. When a governing body is confronted by a technology whose use has potential environmental risks, some form of risk analysis is typically conducted to help decision makers consider the range of possible benefits and harms posed by the technology. Environmental risk assessment (ERA) is a critical component in the governance of nanotechnology and genetically engineered organisms because the uncertainties and complexities surrounding these technologies pose such risk potential. However, GEOs are unique technologies, and there is widespread, international recognition (e.g., the Cartagena Protocol on Biosafety of Living Modified Organisms) that many traditional forms of ERA are not well-suited for evaluating them. Nanotechnology products are also likely to need different models of risk assessment, as there is very little information on their fate, transport, and impacts in the environment.
Science, Ethics, and the “Problems” of Governing Nanotechnologies
Authors: Hogle Linda F.
Published: December 2009

That cacophony you hear is coming from the growing number of commentators addressing ethical, social, and policy issues raised by nanotechnology. Like many novel technologies that disturb the status quo, nanotechnologies raise questions about the adequacy of oversight systems; the extent to which the technologies push legal, moral, and political boundaries; and ultimately, the implications for human health and well-being. Because nanoscale techniques and products challenge our ways of thinking about biology, physics, and chemistry, nanotechnology forces us to reconsider accepted wisdom on toxicity, mutagenicity, contamination, biocompatibility, and other interactions among humans, the environment, and technologies. The sheer scale and reach of nanotechnologies demands institutions, collaborations, and conventions that can cross-link knowledge across organizations, disciplines, and locales. If ever there was an occasion to rethink the limits of disciplinary-specific knowledge, norms about regulatory processes, and societal implications of new technologies, nanotechnologies provide the opportunity.
Risk Communication for Nanobiotechnology: To Whom, About What, and Why?
Authors: Priest Susanna Hornig
Published: December 2009

Regulatory oversight and public communication are intimately intertwined. Oversight failures, both actual and perceived, quickly galvanize attention from both the media and the public, as has occasionally happened in all of the historical cases with which this symposium is concerned — gene therapy, workplace chemicals, drugs and devices, and genetically modified organisms (GMOs), especially those used as (or in) foods. Some developments, such as GMOs, seem to have more cultural significance or “cultural resonance” than others and are especially likely to garner public attention. Developments in nanotechnology, on the other hand, do not seem to have captured as much popular attention. However, the accelerating convergence between nanotechnology as material science and biotechnology, health, and medicine could easily change this situation.
Opioid Contracts and Random Drug Testing for People with Chronic Pain — Think Twice
Authors: Collen Mark
Published: December 2009

It is common for physicians who prescribe opioids for chronic pain to have their patients sign an opioid contract (OC) in order to receive opioid therapy. A vast majority of these contracts contain a stipulation requiring patients to submit to random drug testing (RDT) which screens for both licit and illicit drugs. Physicians who prescribe opioids may be concerned about prosecution and disciplinary actions; medication abuse and misuse; and addiction. Steven Passik et al. write, “…physicians still fear the risk of abuse or addiction as well as the potential legal consequences of their prescribing.”

Issues surrounding OC/RDT need a closer look with a focus on enforceability and efficacy of the opioid contract; accuracy and complications of drug screens and their interpretation; and the importance of trust between patient and physician. In addition, it is vital to dispel fears with facts regarding prosecutions, nonmedical use of prescription opioids, and addiction.
What determines interbank competition? And why should we care?
Authors: Colvin Christopher Louis
Published: December 2009

Traditional measures of competition are inappropriate for banking markets and there exists no consensus alternative measure. As a direct consequence, the empirical relationship between interbank competition and financial stability remains unclear. This paper adopts ideas from the new industrial organisation literature to measure interbank competition in the early twentieth‐century Dutch rural market for small‐scale deposits using newly collected data. It finds that transaction and information switching costs are both important sources of banks' market power.
Family Networks of Obesity and Type 2 Diabetes in Rural Appalachia
Authors: Pancoska Petr , Buch Shama , Cecchetti Alfred , Parmanto Bambang , Vecchio Marcella , Groark Stephen , Paulsen Stephanie , Bardwell Genevieve , Morton Cathy , Chester Ann , Branch Robert
Published: December 2009

The prevalence of obesity and diabetes has been studied in adolescent and adult populations in poor, medically underserved rural Appalachia of West Virginia. A web‐based questionnaire about obesity and diabetes was obtained in 989 family members of 210 Community Based Clinical Research (CBPR) trained adolescent members of a network of 18 science clubs, incorporating 142 families. After age‐correction in < 20 years old, 50% of both adolescents and adults were obese. The frequency distribution of obesity was trimodal. In the overall population 10.4% had type 2 diabetes, while 24% of adult, obese subjects had type 2 diabetes. A new metric, the family diabetes risk potential, identified a trimodal distribution of risk potential. In the lowest most common distribution 43% of families had a diabetic family member. In the intermediate distribution, 69% had a diabetic family member, and in the distribution with highest scores all the families had a diabetic member. In conclusion, the poorest counties of rural Appalachia are at crisis level with the prevalence of obesity and diabetes. The distribution of age‐corrected obesity and family diabetes risk potential are not normally distributed. We suggest that targeting individual family units at greatest risk offers the most efficient strategy for ameliorating this epidemic.
Willem Dicke. Brilliant Clinical Observer and Translational Investigator. Discoverer of the Toxic Cause of Celiac Disease
Authors: Yan David , Holt Peter R.
Published: December 2009

We can admire and learn from physicians with acute clinical acumen and superb approaches to translational research. The observations and studies of Dr. Willem Dicke, a Dutch pediatrician, on the toxic effects of a protein component of wheat and rye demonstrate the highest quality of such investigations. From a clinical observation of one child with celiac disease, through years of historical questioning and empirical dietary suggestions of patient families, he concluded that such foods were toxic. When research became possible after the second world war and fecal fat measures as a hard end point became available he studied 5 children in detail to establish the validity of his clinical clues.
Molecular Characterization of Extended-Spectrum Cephalosporinase-ProducingSalmonella entericaSerovar Choleraesuis Isolates from Patients in Thailand and Denmark
Authors: Sirichote Pantip , Hasman Henrik , Pulsrikarn Chaiwat , Schønheyder Henrik Carl , Samulioniené Jurgita , Pornruangmong Srirat , Bangtrakulnonth Aroon , Aarestrup Frank M. , Hendriksen Rene S.
Published: December 2009

The objective of this study was to characterize extended-spectrum cephalosporinase (ESC)-producing isolates ofSalmonella entericaserovar Choleraesuis recovered from patients in Thailand and Denmark. Twenty-four blood culture isolates from 22 patients were included in the study, of which 23 isolates were recovered from 21 Thai patients during 2003, 2007, or 2008 and one isolate was recovered from a Danish traveler to Thailand. ESC production was confirmed in 13 out of the 24 isolates by MIC testing. Microarray and plasmid profiling (replicon typing and restriction fragment length polymorphism [RFLP]) were used to characterize the genetic mechanisms of antimicrobial resistance in the 13 ESC-producing isolates. Pulsed-field gel electrophoresis (PFGE) and MIC testing were used to compare the clonality between the 13 ESC-producing isolates and the 11 non-ESC-producing isolates. Based on susceptibility patterns, the ESC-producing isolates were more closely related than non-ESC-producing isolates. Microarray, PCR, plasmid profiling, and replicon typing revealed that the 13 ESC-producing isolates harbored eitherblaCMY-2containingincA/CorblaCTX-M-14containingincFIIA,incFrepB, and an unknown replicon located on plasmids ranging in size from 75 to 200 kb. The RFLP and replicon typing clustered the isolates into four distinct groups. PFGE revealed 16 unique patterns and five clusters; each cluster contained two or three of the 24 isolates. The isolate from the Danish patient was indistinguishable from two Thai clinical isolates by PFGE. This study revealed the emergence of theblaCTX-M-14gene among several clones ofSalmonellaserovar Choleraesuis. Numerous plasmids were identified containing up to two different ESC genes and four distinct replicons. A “travel-associated” spread was confirmed. Overall, a high degree of clonal diversity between isolates resistant and susceptible to cephalosporins was observed. The findings represent a serious threat to public health for the Thai people and tourists.
The Latency-Associated Nuclear Antigen Interacts with MeCP2 and Nucleosomes through Separate Domains
Authors: Matsumura Satoko , Persson Linda M. , Wong LaiYee , Wilson Angus C.
Published: December 2009

Kaposi's sarcoma-associated herpesvirus (KSHV)-infected cells express the latency-associated nuclear antigen (LANA) involved in the regulation of host and viral gene expression and maintenance of the KSHV latent episome. Performance of these diverse functions involves a 7-amino-acid chromatin-binding motif (CBM) situated at the amino terminus of LANA that is capable of binding directly to nucleosomes. LANA interacts with additional chromatin components, including methyl-CpG-binding protein 2 (MeCP2). Here, we show that the carboxy-terminal DNA-binding/dimerization domain of LANA provides the principal interaction with MeCP2 but that this association is modulated by the CBM. Both domains are required for LANA to colocalize with MeCP2 at chromocenters, regions of extensive pericentric heterochromatin that can be imaged by fluorescence microscopy. Within MeCP2, the methyl-CpG-binding domain (MBD) is the primary determinant for chromatin localization and acts together with the adjacent repression domains (the transcription repression domain [TRD] and the corepressor-interacting domain [CRID]) to redirect LANA to chromocenters. MeCP2 facilitates repression by LANA bound to the KSHV terminal repeats, a function that requires the MeCP2 C terminus in addition to the MBD and CRID/TRD. LANA and MeCP2 can also cooperate to stimulate transcription of the human E2F1 promoter, which lacks a LANA DNA-binding sequence, but this function requires both the N and C termini of LANA. The ability of LANA to establish multivalent interactions with histones and chromatin-binding proteins such as MeCP2 would enable LANA to direct regulatory complexes to specific chromosomal sites and thereby achieve stable reprogramming of cellular gene expression in latently infected cells.
Temporal patterns of target catch and sea turtle bycatch in the US Atlantic pelagic longline fishing fleet
Authors: Kot Connie Y. , Boustany Andre M. , Halpin Patrick N.
Published: December 2009

Sea turtle bycatch in pelagic longline fishing gear is an ongoing threat to the conservation of sea turtle populations. However, these bycatch events do not occur uniformly in space or time. Leatherback ( Dermochelys coriacea ) and loggerhead ( Caretta caretta ) bycatch rates reported in large fishing regions exhibited different degrees of interannual variability. Target catch and sea turtle bycatch in most regions displayed strong periodicity that corresponded to seasons (~365 days) and/or moon phase (~29 days). When trends in catch and bycatch rates were examined by month and moon phase, the significant periods of higher and lower catch and bycatch related to swordfish ( Xiphias gladius ), yellowfin tuna ( Thunnus albacares ), and sea turtle temporal distributions in foraging and spawning/nesting, oceanographic and prey conditions, and foraging behavior. Catch and bycatch rates tended to depend more on a seasonal rather than a lunar time scale, although there is likely an interaction between the two. These findings provide insights to the susceptibility of target catch and bycatch, regional and temporal patterns of fishing effort, and potential guidance for resource management and conservation.