bluuebunny/crossref_metadata_2025 huggingface dataset:
Phytochemicals and cancer
Authors: Johnson Ian T.
Published: April 2007

Epidemiological studies showing a protective effect of diets rich in fruits and vegetables against cancer have focused attention on the possibility that biologically-active plant secondary metabolites exert anti-carcinogenic activity. This huge group of compounds, now collectively termed ‘phytochemicals’, provides much of the flavour and colour of edible plants and the beverages derived from them. Many of these compounds also exert anti-carcinogenic effects in animal models of cancer, and much progress has been made in defining their many biological activities at the molecular level. Such mechanisms include the detoxification and enhanced excretion of carcinogens, the suppression of inflammatory processes such as cyclooxygenase-2 expression, inhibition of mitosis and the induction of apoptosis at various stages in the progression and promotion of cancer. However, much of the research on phytochemicals has been conductedin vitro, with little regard to the bioavailability and metabolism of the compounds studied. Many phytochemicals present in plant foods are poorly absorbed by human subjects, and this fraction usually undergoes metabolism and rapid excretion. Some compounds that do exert anti-carcinogenic effects at realistic doses may contribute to the putative benefits of plant foods such as berries, brassica vegetables and tea, but further research with human subjects is required to fully confirm and quantify such benefits. Chemoprevention using pharmacological doses of isolated compounds, or the development of ‘customised’ vegetables, may prove valuable but such strategies require a full risk–benefit analysis based on a thorough understanding of the long-term biological effects of what are often surprisingly active compounds.
Life-course approaches to inequalities in adult chronic disease risk
Authors: Smith George Davey
Published: April 2007

A life-course approach to chronic-disease epidemiology uses a multidisciplinary framework to understand the importance of time and timing in associations between exposures and outcomes at the individual and population levels. Such an approach to chronic diseases is enriched by specification of the particular manner in which timing in relation to physical growth, reproduction, infection, social mobility, behavioural transitions etc. can influence various adult chronic diseases in different ways, and more ambitiously by how these temporal processes are interconnected and manifested in health inequalities within a population and in population-level disease trends. The paper will discuss some historical background to life-course epidemiology and theoretical models of life-course processes, and will review some of the empirical evidence linking life-course processes to CHD, haemorrhagic stroke, stomach cancer and other chronic diseases in adulthood. It will also underscore that a life-course approach offers a way to conceptualize how underlying socio-environmental determinants of health, experienced at different life-course stages, can differentially influence the development of chronic diseases, as mediated through proximal specific biological processes.
The psychology of food craving
Authors: Hill Andrew J.
Published: April 2007

Cravings are hedonic responses to food, characterised by their intensity and their specificity. Food cravings are extremely common, reported by the majority of young adults. They are closely associated with liking but not synonymous with increased intake. Structured interviews and prospective incident accounts of food cravings have succeeded in revealing a richness of information about their character, their antecedents and their consequences. In addition, laboratory investigations are adding to what is being learned from field and clinical studies. Taking dieting as an example of an assumed influence on food craving, the outcomes of cross-sectional studies are mixed and unconvincing. Prospective and experimental research shows a clearer relationship. Dieting or restrained eating generally increase the likelihood of food craving while fasting makes craving, like hunger, diminish. Attempted restriction or deprivation of a particular food is associated with an increase in craving for the unavailable food. This relationship suggests a variety of underlying cognitive, conditioning and emotional processes, of which ironic cognitive processes, conditioned cue reactivity and dysphoric mood are prominent. Food cravings may also be self-attributions, accounting for why a highly-palatable but self-restricted food is (over-)consumed. Overall, the popularised account of cravings as elicited by specific nutritional need is having to give way to a more subtle and complex appreciation of human eating behaviour.
CVD risk in South Asians: the importance of defining adiposity and influence of dietary polyunsaturated fat
Authors: Lovegrove Julie A.
Published: April 2007

The prevalence of the metabolic syndrome (MetS), CVD and type 2 diabetes (T2D) is known to be higher in populations from the Indian subcontinent compared with the general UK population. While identification of this increased risk is crucial to allow for effective treatment, there is controversy over the applicability of diagnostic criteria, and particularly measures of adiposity in ethnic minorities. Diagnostic cut-offs for BMI and waist circumference have been largely derived from predominantly white Caucasian populations and, therefore, have been inappropriate and not transferable to Asian groups. Many Asian populations, particularly South Asians, have a higher total and central adiposity for a similar body weight compared with matched Caucasians and greater CVD risk associated with a lower BMI. Although the causes of CVD and T2D are multi-factorial, diet is thought to make a substantial contribution to the development of these diseases. Low dietary intakes and tissue levels of long-chain (LC)n-3 PUFA in South Asian populations have been linked to high-risk abnormalities in the MetS. Conversely, increasing the dietary intake of LCn-3 PUFA in South Asians has proved an effective strategy for correcting such abnormalities as dyslipidaemia in the MetS. Appropriate diagnostic criteria that include a modified definition of adiposity must be in place to facilitate the early detection and thus targeted treatment of increased risk in ethnic minorities.
THE IMPORTANCE OF DEFINING THE FEASIBLE SET
Authors: COWEN TYLER
Published: April 2007

How should we define the feasible set? Even when individuals agree on facts and values, as traditionally construed, different views on feasibility may suffice to produce very different policy conclusions. Focusing on the difficulties in the feasibility concept may help us resolve some policy disagreements, or at least identify the sources of those disagreements. Feasibility is most plausibly a matter of degree rather than of kind. Normative economic reasoning therefore faces a fuzzy social budget constraint. Iterative reasoning about feasibility and desirability may help us overcome these problems.
NEUTRALITY AND PLEASURE
Authors: CRISP ROGER
Published: April 2007

John Broome's ground-breaking Weighing Lives makes precise, and supplies arguments previously lacking for, several views which for centuries have been central to the utilitarian tradition. In gratitude for his enlightening arguments, I shall repay him in this paper by showing how he could make things easier for himself by denying neutrality and accepting hedonism.
REPLIES
Authors: BROOME JOHN
Published: April 2007

I am extremely grateful to the five commentators for readingmy book and offering such interesting thoughts in reaction. Shortage of space may make my responses seem brusque. But of course they are not meant to be.
Intracranial hemorrhage during GliaSite RTS manipulation in an anticoagulated patient
Authors: Gerber David E. , Grossman Stuart A. , Chan Timothy A. , Kleinberg Lawrence
Published: April 2007

The GliaSite radiation therapy system (RTS) is an implantable balloon brachytherapy applicator used to deliver iodine-125 in the treatment of recurrent high-grade gliomas. Patients generally tolerate the procedure well, with only rare reports of adverse events such as wound infection, meningitis, and symptomatic radiation necrosis. Hemorrhagic complications have not been reported. We present a case report describing intracranial hemorrhage during GliaSite manipulation in a patient receiving long-term anticoagulation for a previously diagnosed pulmonary embolism. The GliaSite RTS and the management of venous thromboembolism in patients with brain tumors are reviewed. These events suggest that normalizing coagulation status during GliaSite balloon inflation and deflation should be considered.
Retaining therapy radiographers: What’s so special about us?
Authors: Probst Heidi , Griffiths Sue
Published: April 2007

High therapist vacancy rates and an unsatisfied workforce reduce the opportunity to meet waiting time targets or maintain high standards of care. Current vacancy rates may conceal true staff shortages because of financial pressures. Levels of job satisfaction among the therapy radiographer workforce are presently unknown. A multi-phase study to investigate job satisfaction of therapy radiographers in the United Kingdom is under way. Phase I was an interpretive grounded theory study and, as interviews progressed, a review of the literature on job satisfaction was warranted (in line with the principles of grounded theory). The purpose of this article is to evaluate the literature on job satisfaction as a way to inform the development of retention strategies within the radiotherapy profession. The discussion is focused under the following three themes identified from our phase I study: job design, leadership and organisational governance, stress and burnout. A number of models within the wider literature can inform retention strategies for radiotherapy managers. In particular, the job characteristics model and the model for job-specific well-being adequately identify factors that are relevant to the work of a therapy radiographer. Ensuring mental challenge through job design and continuing professional development opportunities is vital to retaining staff. Support from immediate managers is also a crucial aspect of workers development of intentions to leave. Manager support can moderate experiences of job stress, limiting job dissatisfaction and reducing leaving intentions. Stress and burnout have been cited as significant in reducing job satisfaction in health workers. In the United States, high levels of emotional exhaustion among radiation therapists highlight the potential for the development of burnout within the UK therapy workforce. The discussion looks at the importance of these characteristics within a general retention strategy and recommends future areas of study.
Congenital adrenal hyperplasia: focus on the molecular basis of 21-hydroxylase deficiency
Authors: Gonçalves João , Friães Ana , Moura Luís
Published: April 2007

Congenital adrenal hyperplasia (CAH) is an autosomal recessive disorder caused by defects in one of several steroidogenic enzymes involved in the synthesis of cortisol from cholesterol in the adrenal glands. More than 90% of cases are caused by 21-hydroxylase deficiency, and the severity of the resulting clinical symptoms varies according to the level of 21-hydroxylase activity. 21-Hydroxylase deficiency is usually caused by mutations in theCYP21A2gene, which is located on the RCCX module, a chromosomal region highly prone to genetic recombination events that can result in a wide variety of complex rearrangements, such as gene duplications, gross deletions and gene conversions of variable extensions. Molecular genotyping ofCYP21A2and the RCCX module has proved useful for a more accurate diagnosis of the disease, and prenatal diagnosis. This article summarises the clinical features of 21-hydroxylase deficiency, explains current understanding of the disease at the molecular level, and highlights recent developments, particularly in diagnosis.
Referenzgruppeneffekte im Sportunterricht
Authors: Gerlach Erin , Trautwein Ulrich , Lüdtke Oliver
Published: April 2007

Zusammenfassung: Der big-fish-little-pond effect beschreibt das Phänomen, dass vergleichbar leistungsstarke Schülerinnen und Schüler in leistungsstärkeren Lerngruppen infolge sozialer Vergleiche niedrigere Fähigkeitsselbstkonzepte ausbilden als in Gruppen mit einem niedrigeren mittleren Leistungsniveau. In der vorliegenden Studie wird geprüft, ob dieser Effekt auch im Hinblick auf das sportbezogene Selbstkonzept zu finden ist. In einer längsschnittlich angelegten Studie wurde eine repräsentative Stichprobe von 1185 Schülerinnen und Schülern in der Grundschule (3. Klasse) und der Sekundarstufe I (6. Klasse) mit einem motorischen Test und per Fragebögen untersucht. In Mehrebenenanalysen konnte ein negativer Effekt der durchschnittlichen Sportleistung einer Klasse auf das sportbezogene Selbstkonzept der Schüler nachgewiesen werden, der auch noch nach dem Übergang in die Sekundarstufe I andauerte. Die Konfrontation mit sportlichen Mitschülern hat demnach persistente negative Effekte auf das sportbezogene Selbstkonzept.
Demographische “Diversity” in Sportteams
Authors: Kearney Eric
Published: April 2007

Zusammenfassung: Im Kontext von Fußballteams im Amateurbereich untersucht die vorliegende Arbeit den Einfluss von “Diversity” bezüglich Nationalität auf das Ausmaß an sozialer Integration und emotionalen Konflikten. Eine querschnittliche Studie an 42 Teams zeigt, dass die Teamzusammengehörigkeitsdauer den Zusammenhang zwischen “Diversity” bezüglich Nationalität und sozialer Integration moderiert: Bei geringer Teamzugehörigkeitsdauer war dieser Zusammenhang negativ, bei langer Teamzugehörigkeitsdauer dagegen nicht mehr signifikant. Eine analoge Hypothese hinsichtlich des Ausmaßes an emotionalen Konflikten bestätigte sich nicht. Die Ergebnisse werden dahingehend interpretiert, dass der negative Einfluss von demographischer Team-“Diversity” auf die soziale Integration unter bestimmten Voraussetzungen im Laufe der Zeit abnimmt.
Die Validität von Auswahlgesprächen im Rahmen der Hochschulzulassung - eine Metaanalyse
Authors: Hell Benedikt , Trapmann Sabrina , Weigand Sonja , Schuler Heinz
Published: April 2007

Zusammenfassung. Das Interesse an Kriterien und eignungsdiagnostischen Verfahren zur Auswahl von Studierenden im Rahmen der Hochschulzulassung hat in den vergangenen Jahren im deutschsprachigen Raum stark zugenommen. Während die Deutsche Gesellschaft für Psychologie (1997) Auswahlgesprächen kritisch gegenübersteht, wird der Einsatz dieser Verfahrensklasse von verschiedenen Hochschulvertretern und Bildungspolitikern befürwortet. Zur Bestimmung der prognostischen Validität von Interviews im Rahmen der Hochschulzulassung wird eine Metaanalyse von k = 44 Einzelstudien durchgeführt, die Auswahlgespräche als Prädiktor und Studiennoten als Erfolgskriterium berücksichtigen. Die mittlere korrigierte Validität von Interviews beträgt ρ = .16. Von insgesamt 11 geprüften Moderatoren der Validität erweist sich der Strukturiertheitsgrad der Interviews als bedeutsam. Unstrukturierte Interviews erreichen eine korrigierte Validität von ρ = .11 gegenüber einer korrigierten Validität von ρ = .21 für strukturierte Varianten dieser Verfahrensklasse. Die für strukturierte und unstrukturierte Auswahlgespräche berechneten Validitätskoeffizienten sind generalisierbar. Die inkrementelle Validität von Auswahlgesprächen gegenüber Schulnoten und Studierfähigkeitstests ist gering.
Dynamic and regression modeling of ocean variability in the tide‐gauge record at seasonal and longer periods
Authors: Hill Emma M. , Ponte Rui M. , Davis James L.
Published: April 2007

Comparison of monthly mean tide‐gauge time series to corresponding model time series based on a static inverted barometer (IB) for pressure‐driven fluctuations and a ocean general circulation model (OM) reveals that the combined model successfully reproduces seasonal and interannual changes in relative sea level at many stations. Removal of the OM and IB from the tide‐gauge record produces residual time series with a mean global variance reduction of 53%. The OM is mis‐scaled for certain regions, and 68% of the residual time series contain a significant seasonal variability after removal of the OM and IB from the tide‐gauge data. Including OM admittance parameters and seasonal coefficients in a regression model for each station, with IB also removed, produces residual time series with mean global variance reduction of 71%. Examination of the regional improvement in variance caused by scaling the OM, including seasonal terms, or both, indicates weakness in the model at predicting sea‐level variation for constricted ocean regions. The model is particularly effective at reproducing sea‐level variation for stations in North America, Europe, and Japan. The RMS residual for many stations in these areas is 25–35 mm. The production of “cleaner” tide‐gauge time series, with oceanographic variability removed, is important for future analysis of nonsecular and regionally differing sea‐level variations. Understanding the ocean model's strengths and weaknesses will allow for future improvements of the model.
Summer formation of a high‐nutrient low‐oxygen pool in Cape Cod Bay, USA
Authors: Jiang Mingshun , Wallace Gordon T. , Zhou Meng , Libby Scott , Hunt Carlton D.
Published: April 2007

The Boston Harbor, Massachusetts Bay (MB), and Cape Cod Bay (CCB) system (MBS) is a semienclosed coastal embayment located in the Gulf of Maine. As the southern portion of the MBS, CCB is connected to MB by the coastal transport that varies seasonally. Observations have revealed that during every summer, nutrients accumulate below the thermocline in central CCB associated with relatively low dissolved oxygen (DO) concentrations. To understand the remote and local causes in the formation of this pool of high‐nutrient and low‐oxygen (HNLO) bottom water, a modeling study was conducted using a coupled physical‐biogeochemical model. A 4‐year simulation (1998–2001) indicated the persistent presence of this HNLO feature. A detailed analysis of modeled and observed results for 2000 suggested that three factors controlled the formation of the HNLO pool in the summer: (1) southward coastal transport of organic matter from MB into CCB in winter and spring, (2) a relatively long residence time in CCB favoring sedimentation of organic matter throughout the year, and (3) high temperature and strong stratification resulting in intensive regeneration (sediment and water column) and accumulation of nutrients below the thermocline in summer and fall. The magnitude and spatiotemporal scales of this HNLO pool were determined by the available amount of organic matter, stability of stratification, isolation of CCB, and wind‐induced lateral transport and mixing. This HNLO pool may significantly impact the biogeochemical processes and ecosystem dynamics in CCB.
Radiocarbon age offsets of foraminifera resulting from differential dissolution and fragmentation within the sedimentary bioturbated zone
Authors: Barker Stephen , Broecker Wallace , Clark Elizabeth , Hajdas Irka
Published: April 2007

Shells of coexisting species of planktonic foraminifera from the Ontong Java Plateau reveal radiocarbon age offsets of up to 2200 years. Similar offsets are found between fragments and whole shells of single species. Steady state modelling of dissolution and bioturbation within the sedimentary mixed layer predicts age differences of up to several kiloyears due to the interplay between differential dissolution and fragmentation of foraminifer shells and bioturbation. The observation that fragile foraminiferal shells are systematically older than those of more robust species is more difficult to explain. Mechanisms of chemical erosion, interface dissolution, and sediment redistribution are all apparently unable to explain this phenomenon. A possible solution is presented in which a particular species may be represented by two distinct classes of shells which are more or less robust. In this case, differential dissolution and fragmentation causes an increase in the mean age as the fragile class contributes less to the remaining intact shells. This study highlights the vulnerability of low sedimentation rate cores to the effects of dissolution and bioturbation.
Tectonic denudation and topographic development in the Spanish Sierra Nevada
Authors: Reinhardt L. J. , Dempster T. J. , Shroder J. F. , Persano C.
Published: April 2007

The denudation history of the rapidly uplifting western part of the Spanish Sierra Nevada was assessed using apatite fission track (AFT) ages and 10Be analyses of bedrock and fluvial sediments. Major contrasts in the denudation history are recorded within the 27 km2 Río Torrente catchment. Upland areas are characterized by low‐relief, low slope angles, and locally the preservation of shallow marine sediments, which have experienced <200 m of erosion in the last 9 Myr. However, AFT age determinations from samples collected close to the marine sediments imply >2 km of denudation since circa 4 Ma. The minimum denudation rates of 0.4 mm yr−1 derived from AFT also contrast with the slow medium‐term (104 years) erosion rates (0.044 ± 0.015 mm yr−1) estimated from 10Be measurements at high elevations. The local medium‐long‐term contrasts in denudation rates within the high Sierra Nevada indicate that much of the unroofing occurs by tectonic denudation on flat‐lying detachments. In lower elevation parts of the catchment, rapid river incision coupled to rock uplift has produced ∼1.6 km of relief, implying that the rivers and adjacent hillslopes close to the edge of the orogen are sensitive to normal‐fault‐driven changes in base level. However, these changes are not transmitted into the low‐relief slowly eroding upland areas. Thus the core of the mountain range continues to increase in elevation until the limits of crustal strength are reached and denudation is initiated along planes of structural weakness. We propose that this form of tectonic denudation provides an effective limit to relief in young orogens.
Arctic sea ice decline: Faster than forecast
Authors: Stroeve Julienne , Holland Marika M. , Meier Walt , Scambos Ted , Serreze Mark
Published: April 2007

From 1953 to 2006, Arctic sea ice extent at the end of the melt season in September has declined sharply. All models participating in the Intergovernmental Panel on Climate Change Fourth Assessment Report (IPCC AR4) show declining Arctic ice cover over this period. However, depending on the time window for analysis, none or very few individual model simulations show trends comparable to observations. If the multi‐model ensemble mean time series provides a true representation of forced change by greenhouse gas (GHG) loading, 33–38% of the observed September trend from 1953–2006 is externally forced, growing to 47–57% from 1979–2006. Given evidence that as a group, the models underestimate the GHG response, the externally forced component may be larger. While both observed and modeled Antarctic winter trends are small, comparisons for summer are confounded by generally poor model performance.
The Ecological Paradigm of Mind and Its Implications for Psychotherapy
Authors: Oliver Luis Enrique , Ostrofsky Richard
Published: April 2007

As the result of a tremendous cross-disciplinary effort, the past 20 years have witnessed huge advances in our understanding of the brain and of the brain's relationship to the mind. A new paradigm of the mind—an ecological paradigm, as Gregory Bateson called it in 1973—has fallen into place. The authors have begun to have a scientific, biologically grounded explanation of how the human brain–mind system works. Despite the likely relevance of this paradigm for psychotherapy, its uptake in the clinical literature has been uneven to date. Accordingly, this article aims to pique the interest of the psychotherapeutic community in the ecological paradigm as a whole, in hopes of stimulating wider discussion and research into its clinical aspects and consequences.
Self, Identity, and Globalization in Times of Uncertainty: A Dialogical Analysis
Authors: Hermans Hubert J. M. , Dimaggio Giancarlo
Published: April 2007

Our era is witnessing an increasing impact of globalization on self and identity and at the same time a growing uncertainty. The experience of uncertainty motivates individuals and groups to find local niches for identity construction. This article's central tenet is that the processes of globalization and localization, as globalization's counterforce, require a dialogical conceptualization of self and identity in which global and local voices are involved in continuous interchanges and negotiations. This tenet is elaborated along 2 lines of argument. First, 3 factors are described as crucial to understanding the processes of globalization and localization on the individual level: the increasing number of voices and countervoices, the role of social power, and the role of emotions. Second, the authors argue that the apparent tension between the widening horizons of globalization and the need for local niches requires acknowledgment of the pervasive influence of biologically based needs for stability, safety, and security. Finally, the authors propose studying self and identity on 3 levels—individual, local, and global—and some lines of research at the interface of these levels.
Measuring Spirituality and Spiritual Emptiness: Toward Ecumenicity and Transcultural Applicability
Authors: Ho David Y. F. , Ho Rainbow T. H.
Published: April 2007

The authors review Eastern and Western conceptions of spirituality, explicate the spirituality construct and differentiate it from religiosity, propose strategies for achieving ecumenicity and transcultural applicability, and suggest innovative techniques for measuring spirituality and spiritual emptiness. The essential attributes of ecumenical spirituality are that it (a) is concerned with existential or transcendent questions; (b) belongs to the domain of cardinal values underlying all aspects of life; and (c) is self-reflective, and hence metacognitive, in nature. The paths to spirituality are many and are grounded in different values and beliefs across philosophical-religious traditions. However, commonalities may be extracted at a high level of abstraction and with maximal inclusiveness. Thus, the goal of ecumenicity, and hence transcultural applicability, is attainable.
Physiological and pathological changes in the redox state of human serum albumin critically influence its binding properties
Authors: Oettl K , Stauber R E
Published: April 2007

Binding and transport of a number of endogenous and exogenous compounds is an important function of the main plasma protein, albumin. In vivo and in vitro, albumin may be oxidatively modified in different ways with different agents at different sites. These modifications have various consequences on the physiological functions of albumin. Diabetes mellitus, liver diseases and nephropathy are just a few examples of disorders in which oxidative stress is involved and altered albumin functions have been described. This review is focussed on the consequences of oxidative modification on the binding properties of albumin. These range from no effect to decreased or increased binding affinities depending on the ligand under investigation and the type of modification. Indicators for modification include glycosylation, disulphide formation or the content of carbonyl groups. The redox state of albumin can affect the binding properties in several ways, including altered conformation and consequently altered affinities at binding sites and altered binding when the binding reaction itself is redox sensitive. The physiological or pathophysiological concentrations of different oxidatively modified albumin molecules vary over a wide range and are crucial in assessing the clinical relevance of altered ligand binding properties of a particularly modified albumin species in various disease conditions.

British Journal of Pharmacology (2007) 151, 580–590; doi:10.1038/sj.bjp.0707251
Discovery of P2X7 receptor‐selective antagonists offers new insights into P2X7 receptor function and indicates a role in chronic pain states
Authors: Donnelly‐Roberts D L , Jarvis M F
Published: April 2007

ATP‐sensitive P2X7 receptors are localized on cells of immunological origin including peripheral macrophages and glial cells in the CNS. Activation of P2X7 receptors leads to rapid changes in intracellular calcium concentrations, release of the proinflammatory cytokine interleukin‐1β and following prolonged agonist exposure, the formation of cytolytic pores in plasma membranes. Both the localization and functional consequences of P2X7 receptor activation indicate a role in inflammatory processes. The phenotype of P2X7 receptor gene‐disrupted mice also indicates that P2X7 receptor activation contributes to ongoing inflammation. More recently, P2X7 receptor knockout data has also suggested a specific role in inflammatory and neuropathic pain states. The recent discovery of potent and highly selective antagonists for P2X7 receptors has helped to further clarify P2X receptor pharmacology, expanded understanding of P2X7 receptor signaling, and offers new evidence that P2X7 receptors play a specific role in nociceptive signaling in chronic pain states. In this review, we incorporate the recent discoveries of novel P2X7 receptor‐selective antagonists with a brief update on P2X7 receptor pharmacology and its therapeutic potential.

British Journal of Pharmacology (2007) 151, 571–579; doi:10.1038/sj.bjp.0707265
Role of neutrophil elastase in LTB4‐induced neutrophil transmigration in vivo assessed with a specific inhibitor and neutrophil elastase deficient mice
Authors: Young R E , Voisin M‐B , Wang S , Dangerfield J , Nourshargh S
Published: April 2007

Background and purpose:

The serine protease neutrophil elastase (NE) appears to regulate inflammatory responses at multiple levels but its role in leukocyte transmigration in vivo remains unclear. The present study aimed to address this issue by using both an NE inhibitor (ONO‐5046) and NE deficient (NE−/−) mice.

Experimental approach:

A number of inflammatory mediators (LTB4, KC and PAF) were investigated in vitro for their ability to stimulate the release and the surface expression of NE by neutrophils. In addition, the role of NE in leukocyte migration elicited by topical LTB4 was investigated in vivo in mouse cremasteric venules as observed by intravital microscopy.

Key results:

Amongst the mediators tested in vitro, LTB4 was found to be a highly potent and efficacious inducer of NE cell surface expression on murine neutrophils. Furthermore, in wild‐type mice (WT), LTB4‐induced leukocyte transmigration was reduced by intravenous ONO‐5046 (66% inhibition), an effect that appeared to occur at the level of the perivascular basement membrane. Interestingly, LTB4‐induced responses were normal in NE−/− mice and, while ONO‐5046 had no inhibitory effect in these animals, the broad‐spectrum serine protease inhibitor aprotinin suppressed leukocyte transmigration in both WT and NE−/− mice.

Conclusions and implications:

The findings demonstrate the potent ability of LTB4 to induce cell‐surface expression of NE and provide evidence for the involvement of NE in LTB4‐induced neutrophil transmigration in vivo. The results also suggest the existence of compensatory mechanisms in NE−/− mice, highlighting the added value of investigating pharmacological blockers in parallel with genetic deletion.

British Journal of Pharmacology (2007) 151, 628–637; doi:10.1038/sj.bjp.0707267
Crocetin attenuates palmitate‐induced insulin insensitivity and disordered tumor necrosis factor‐α and adiponectin expression in rat adipocytes
Authors: Xi L , Qian Z , Xu G , Zhou C , Sun S
Published: April 2007

Background and purpose:

A number of studies have implicated adipocyte‐derived factors in the development of insulin resistance. Intracellular redox status has been reported to play a significant role in the modulation of insulin action. This study was designed to investigate the potential of crocetin, a potent antioxidant, to protect adipocytes against the induction of insulin insensitivity and disordered expression of tumor necrosis factor (TNF)‐α and adiponectin in vitro.

Experimental approach:

We used palmitate to induce insulin resistance in freshly isolated rat adipocytes, and observed the effect of crocetin, N‐acetylcysteine, diphenyleneiodonium, rotenone and oxypurinol. Insulin sensitivity was measured using 2‐deoxy‐D‐[1‐3H]‐glucose uptake assay. Levels of glucose transporter 4, TNF‐α and adiponectin were evaluated by immunoblot analysis, and levels of mRNA for TNF‐α and adiponectin by reverse transcription‐polymerase chain reaction analysis. Intracellular production of reactive oxygen species (ROS) was determined spectrofluorometrically using 2′,7′‐dichlorofluorescin diacetate.

Key results:

Palmitate induced a 45% decrease in insulin‐stimulated glucose uptake in adipocytes. The mRNA and protein expression of TNF‐α were enhanced by 64% and 59% respectively whereas the mRNA and protein expression of adiponectin were reduced by 43% and 36% respectively by palmitate treatment. These changes were accompanied by a 54% increase in intracellular ROS levels. Crocetin, N‐acetylcysteine and diphenyleneiodonium were found to attenuate these abnormalities.

Conclusions and Implications:

Crocetin blocked the impaired insulin‐stimulated glucose uptake and disordered TNF‐α and adiponectin expression induced by palmitate in rat adipocytes. Inactivation of NADPH oxidase may account for these observations.

British Journal of Pharmacology (2007) 151, 610–617; doi:10.1038/sj.bjp.0707276
Geometric gyrokinetic theory for edge plasmas
Authors: Qin H. , Cohen R. H. , Nevins W. M. , Xu X. Q.
Published: April 2007

It turns out that gyrokinetic theory can be geometrically formulated as a special case of a geometrically generalized Vlasov-Maxwell system. It is proposed that the phase space of the space-time is a seven-dimensional fiber bundle P over the four-dimensional space-time M, and that a Poincaré-Cartan-Einstein 1-form γ on the seven-dimensional phase space determines a particle's worldline in the phase space. Through Liouville 6-form Ω and fiber integral, the 1-form γ also uniquely defines a geometrically generalized Vlasov-Maxwell system as a field theory for the collective electromagnetic field. The geometric gyrokinetic theory is then developed as a special case of the geometrically generalized Vlasov-Maxwell system. In its most general form, gyrokinetic theory is about a symmetry, called gyrosymmetry, for magnetized plasmas, and the 1-form γ again uniquely defines the gyrosymmetry. The objective is to decouple the gyrophase dynamics from the rest of the particle dynamics by finding the gyrosymmetry in γ. Compared to other methods of deriving the gyrokinetic equations, the advantage of the geometric approach is that it allows any approximation based on mathematical simplification or physical intuition to be made at the 1-form level, and yet the field theories still have the desirable exact conservation properties, such as phase space volume conservation and energy-momentum conservation if the 1-form does not depend on the space-time coordinate explicitly. A set of generalized gyrokinetic equations valid for the edge plasmas is then derived using this geometric method. This formalism allows large-amplitude, time-dependent background electromagnetic fields to be developed fully nonlinearly in addition to small-amplitude, short-wavelength electromagnetic perturbations. The fact that we adopted the geometric method in the present study does not necessarily imply that the major results reported here cannot be achieved using classical methods. What the geometric method offers is a systematic treatment and simplified calculations.
Characterization of Mn-doped 3C-SiC prepared by ion implantation
Authors: Takano Fumiyoshi , Wang Wenhong , Akinaga Hiro , Ofuchi Hironori , Hishiki Shigeomi , Ohshima Takeshi
Published: April 2007

The characterization of Mn-doped 3C-SiC prepared by ion implantation is reported. Implantation of Mn ions at a dose of 1×1016cm−2 into a 3C-SiC homoepitaxial wafer was carried out. High temperature annealing following the implantation process was found to enhance the ferromagnetic ordering. Transmission magnetic circular dichroism and magnetization investigations demonstrated a ferromagnetic behavior below 245K. The lattice relaxation induced by the postannealing is considered a possible mechanism of this outcome.
Surface properties of Zr50Cu40Al10 bulk metallic glass
Authors: Nakayama Koji S. , Yokoyama Y. , Sakurai T. , Inoue A.
Published: April 2007

Atomic force microscope (AFM) makes it possible to image the surface morphological evolutions of the Zr50Cu40Al10 bulk metallic glass (BMG). The heating in vacuum leads to the creation of nanoclusters and the significant structural changes driven by viscous flow. Auger electron spectroscopy confirms that the nanoclusters correspond to zirconium oxide. Furthermore, the nanoclusters do not influence the crystallization process of the BMG but the viscous flow is crucial to surface modification. The temperature dependent AFM observation combined with chemical analysis is a new protocol to study fundamental properties of BMG surfaces.
Quasi–in situ neutron tomography on polymer electrolyte membrane fuel cell stacks
Authors: Manke I. , Hartnig Ch. , Grünerbel M. , Kaczerowski J. , Lehnert W. , Kardjilov N. , Hilger A. , Banhart J. , Treimer W. , Strobl M.
Published: April 2007

Quasi–in situ neutron tomography is applied to polymer electrolyte membrane fuel cell stacks for a cell-by-cell detection of liquid water agglomerates. Water distributions in the corresponding anodic and cathodic flow fields are analyzed separately. The influence of the membrane thickness as well as effects of the electro-osmotic drag and of back-diffusion from the cathode to the anode on the water distribution are investigated. Furthermore, the well-known engineering problem of the anomalous behavior of the outermost cells in long multistacks is addressed. The suitability of neutron tomography to support the development of fuel cells is shown.
Hydration effect on the structure of dioleoylphosphatidylcholine bilayers
Authors: Caracciolo Giulio , Pozzi Daniela , Caminiti Ruggero
Published: April 2007

In situ enersgy dispersive x-ray diffraction was used to study the effect of hydration on the structure of dioleoylphosphatidylcholine (DOPC) bilayers in the biologically relevant liquid-crystalline phase. A broad range of relative humidity (RH) was investigated (0.45<RH<1) and two hydration regimes were found. From RH=0.45 up to RH∼0.94, the structure of DOPC bilayers was found to change slightly. At RH∼0.94, a distinctive structural change was observed. From RH∼0.94 up to full hydration, a strong increase in the head group size, coupled with a marked decrease in the hydrophobic core thickness, was observed. Possible molecular mechanisms underlying experimental observations are discussed.
Upconversion with ultrabroad excitation band: Simultaneous use of two sensitizers
Authors: Baluschev S. , Yakutkin V. , Wegner G. , Miteva T. , Nelles G. , Yasuda A. , Chernov S. , Aleshchenkov S. , Cheprakov A.
Published: April 2007

The authors demonstrate the ability to combine sensitizers effectively working with single emitter in order to increase the excitation window for noncoherent upconversion. They show effective upconversion of the red part of the sun spectrum realized by ultralow excitation intensity (as low as 1Wcm−2) and ultrabroad excitation spectrum (Δλ∼80nm).
Size-dependent radiative lifetime in vertically stacked (In,Ga)As quantum dot structures
Authors: Zhang Y. C. , Pancholi A. , Stoleru V. G.
Published: April 2007

The radiative lifetime dependence on the dot size in multilayer (In,Ga)As quantum dot structures with different thickness GaAs barriers was studied via photoluminescence. In the structure with thick barriers and isolated dots, the radiative lifetime increased monotonically with the dot size, which was attributed to the enhanced exciton oscillator strength in smaller dots. By contrast, in the structure with thin barriers and electronically coupled vertically adjacent dots, the radiative lifetime increased and later decreased with increasing dot size. This can be explained by the enhancement of the exciton oscillator strength in larger dots, which are coherently coupled through vertical tunneling.
Shear strain in a shear band of a bulk-metallic glass in compression
Authors: Jiang W. H. , Liu F. X. , Liaw P. K. , Choo H.
Published: April 2007

Using an infrared camera, the authors observe in situ the dynamic shear-banding operations in the geometrically constrained specimens of a bulk-metallic glass during compression at various strain rates. Based on the observed number of shear bands in a collection of simultaneous shear-banding operations that cause a serration, the authors calculate the shear strains in individual shear bands. The results demonstrate that the shear strain in a shear band is up to 103%–104% and dependent on strain rates. The higher the strain rates, the larger the strain in a shear band.
Solid solution alloys of AlCoCrFeNiTix with excellent room-temperature mechanical properties
Authors: Zhou Y. J. , Zhang Y. , Wang Y. L. , Chen G. L.
Published: April 2007

Alloys with composition of AlCoCrFeNiTix (x: molar ratio; x=0,0.5,1,1.5) were designed by using the strategy of equiatomic ratio and high entropy of mixing. The alloy system is composed mainly of body centered cubic solid solution and possesses excellent room-temperature compressive mechanical properties. Particularly for AlCoCrFeNiTi0.5 alloy, the yield stress, fracture strength, and plastic strain are as high as 2.26GPa, 3.14GPa, and 23.3%, respectively, which are superior to most of the high-strength alloys such as bulk metallic glasses.
Age Decline in the Activity of the Ca2+-sensitive K+ Channel of Human Red Blood Cells
Authors: Tiffert Teresa , Daw Nuala , Etzion Zipora , Bookchin Robert M. , Lew Virgilio L.
Published: April 2007

The Ca2+-sensitive K+ channel of human red blood cells (RBCs) (Gardos channel, hIK1, hSK4) was implicated in the progressive densification of RBCs during normal senescence and in the mechanism of sickle cell dehydration. Saturating RBC Ca2+ loads were shown before to induce rapid and homogeneous dehydration, suggesting that Gardos channel capacity was uniform among the RBCs, regardless of age. Using glycated hemoglobin as a reliable RBC age marker, we investigated the age–activity relation of Gardos channels by measuring the mean age of RBC subpopulations exceeding a set high density boundary during dehydration. When K+ permeabilization was induced with valinomycin, the oldest and densest cells, which started nearest to the set density boundary, crossed it first, reflecting conservation of the normal age–density distribution pattern during dehydration. However, when Ca2+ loads were used to induce maximal K+ fluxes via Gardos channels in all RBCs (Fmax), the youngest RBCs passed the boundary first, ahead of the older RBCs, indicating that Gardos channel Fmax was highest in those young RBCs, and that the previously observed appearance of uniform dehydration concealed a substantial degree of age scrambling during the dehydration process. Further analysis of the Gardos channel age–activity relation revealed a monotonic decline in Fmax with cell age, with a broad quasi-Gaussian Fmax distribution among the RBCs.
SPACER: identification ofcis-regulatory elements with non-contiguous critical residues
Authors: Chakravarty Arijit , Carlson Jonathan M. , Khetani Radhika S. , DeZiel Charles E. , Gross Robert H.
Published: April 2007

Motivation: Many transcription factors bind to sites that are long and loosely related to each other. De novo identification of such motifs is computationally challenging. In this article, we propose a novel semi-greedy algorithm over the space of all IUPAC degenerate strings to identify the most over-represented highly degenerate motifs.

Results: We present an implementation of this algorithm, named SPACER (Separated Pattern-based Algorithm for cis-Element Recognition) and demonstrate its effectiveness in identifying ‘gapped’ and highly degenerate motifs. We compare SPACER's performance against ten motif finders on 42 experimentally defined regulons from Bacillus subtilis, Escherichia coli and Saccharomyces cerevisiae. These motif finders cover a wide range of both enumerative and statistical approaches, including programs specifically designed for prokaryotic and ‘gapped’ motifs.

Availability: A Java 1.4 implementation is freely available on the Web at http://genie.Dartmouth.edu/SPACER/

Contact:  robert.h.gross@dartmouth.edu

Supplementary information: Supplementary data are available at Bioinformatics online.
Temporal and epigenetic regulation of neurodevelopmental plasticity
Authors: Allen Nicholas D
Published: April 2007

The anticipated therapeutic uses of neural stem cells depend on their ability to retain a certain level of developmental plasticity. In particular, cells must respond to developmental manipulations designed to specify precise neural fates. Studiesin vivoandin vitrohave shown that the developmental potential of neural progenitor cells changes and becomes progressively restricted with time. Forin vitrocultured neural progenitors, it is those derived from embryonic stem cells that exhibit the greatest developmental potential. It is clear that both extrinsic and intrinsic mechanisms determine the developmental potential of neural progenitors and that epigenetic, or chromatin structural, changes regulate and coordinate hierarchical changes in fate-determining gene expression. Here, we review the temporal changes in developmental plasticity of neural progenitor cells and discuss the epigenetic mechanisms that underpin these changes. We propose that understanding the processes of epigenetic programming within the neural lineage is likely to lead to the development of more rationale strategies for cell reprogramming that may be used to expand the developmental potential of otherwise restricted progenitor populations.
Genomic analysis of genetic markers associated with inherited cardiomyopathy (round heart disease) in the turkey (Meleagris gallopavo)
Authors: Reed K. M. , Mendoza K. M. , Hu G. R. , Sullivan L. R. , Grace M. W. , Chaves L. D. , Kooyman D. L.
Published: April 2007

In turkeys, spontaneous cardiomyopathy or round heart (RH) disease is characterised by dilated ventricles and cardiac muscle hypertrophy. Although the aetiology of RH is still unknown, the disease can have a significant economic impact on turkey producers. In an initial attempt to identify genomic regions associated with RH, we utilised the chicken genome sequence to target short DNA sequences (sequence‐characterised amplified regions, SCARs) identified in previous studies that had significant differences in frequency distribution between RH+ and RH− turkeys. SCARs were comparatively aligned with the chicken whole‐genome sequence to identify flanking regions for primer design. Primers from 32 alignments were tested and target sequences were successfully amplified for 30 loci (94%). Comparative re‐sequencing identified putative SNPs in 20 of the 30 loci (67%). Genetically informative SNPs at 16 loci were genotyped in the UMN/NTBF turkey mapping population. As a result of this study, 34 markers were placed on the turkey/chicken comparative map and 15 markers were added to the turkey genetic linkage map. The position of these markers relative to cardiac‐related genes is presented. In addition, analysis of genotypes at 109 microsatellite loci presumed to flank the SCAR sequences in the turkey genome identified four significant associations with RH.