bluuebunny/crossref_metadata_2025 huggingface dataset:
The role of quenched‐in vacancies for the decomposition of aluminium alloys
Authors: Klobes B. , Staab T. E. M. , Haaks M. , Maier K. , Wieler I.
Published: July 2008

The very early stages of decomposition during room temperature storage, i.e. just a few minutes after quenching, are investigated by positron annihilation lifetime spectroscopy for both an AlMgSi alloy and an AlCuMg alloy. It turns out that by freezing the decomposition kinetics during measurements we can detect vacancy–solute atom pairs. The formation of larger solute clusters with structural vacancies is seen by an increase of the mean positron lifetime in the course of storage at room temperature (RT). Earlier findings concerning aging at RT were unable to discover this effect. The detected changes are interpreted in terms of cluster formation. Thus we show that positron annihilation spectroscopy (PAS) is one of the very few methods to access early stages of decomposition in metallic alloys. Moreover, the lower limit of the concentration of quenched‐in vacancy‐like defects is calculated to be at least 2 × 10–5 per atom. (© 2008 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Mapping the electrical properties of semiconductor junctions—the electron holographic approach
Authors: Twitchett‐Harrison Alison C. , Dunin‐Borkowski Rafal E. , Midgley Paul A.
Published: July 2008

The need to determine the electrical properties of semiconductor junctions with high spatial resolution is as pressing now as ever. One technique that offers the possibility of quantitative high‐resolution mapping of two‐ and three‐dimensional electrostatic potential distributions is off‐axis electron holography. In this study, we review some of the issues associated with interpreting phase shifts measured using off‐axis electron holography, and we describe how a quantitative determination of the dopant‐related electrostatic potential can be achieved for device structures. Issues that include the presence of surface “dead” layers, external electrostatic fringing fields, variations in specimen thickness and dynamical diffraction are discussed, and their impact on the quantification of results obtained using off‐axis electron holography is examined. SCANNING 30: 299–309, 2008. © 2008 Wiley Periodicals, Inc.
Chimpanzee (Pan troglodytes) responses to caregiver use of chimpanzee behaviors
Authors: Jensvold Mary Lee Abshire
Published: July 2008

The relationships between captive primates and their caregivers are critical ones and can affect animal welfare. Friendly relationships can improve quality of life; adversely, agonistic relationships can decrease quality of life. Caregivers in and of themselves should not be stressful to their charges, instead the caregivers' behaviors and the nature of their interactions with captive primates is likely the basis for the stress. One method to promote positive relationships in the captive environment is for caregivers to employ species‐specific behaviors in their interactions with their charges. This study tested the effect of caregivers' use of these behaviors with chimpanzees at The Zoo Northwest Florida in Gulf Breeze. The chimpanzee participants were three males. Data collection occurred during typical interactions between the human participants and the chimpanzees. Some days the caregiver presented chimpanzee behaviors and vocalizations (CB—Chimpanzee Behavior Condition) in the data collection interactions with the chimpanzees. On other days the caregiver presented human behaviors and used speech (HB—Human Behavior Condition) in the interactions with the chimpanzees. The interactions were videotaped. Data coders recorded the behavioral contexts for each chimpanzee as they occurred on the videotape and the time that each context began. Overall they engaged in significantly more friendly behaviors such as play in CB than in HB. They were significantly less interactive in HB than CB. Caregivers should understand and employ species‐specific interactions with chimpanzees to promote friendly interactions and animal welfare. Zoo Biol 27:345–359, 2008. © 2008 Wiley‐Liss, Inc.
Differential Effects of Strategic Planning on Community Change in Two Urban Neighborhood Coalitions
Authors: Watson-Thompson Jomella , Fawcett Stephen B. , Schultz Jerry A.
Published: July 2008

Community coalitions represent a promising approach for addressing the interrelated and multiply‐ determined issues affecting urban neighborhoods of concentrated poverty. The literature suggests a number of community processes that may affect coalition efforts to change and improve communities. This study uses an interrupted time‐series design to examine the effects of a strategic planning intervention on community change in two urban neighborhoods in the Kansas City metropolitan area. Results showed that strategic planning was associated with increased rates of community change in the two urban neighborhood coalitions. Under appropriate conditions, such as the presence of consistent leadership, strategic planning may be a particularly effective mechanism for stimulating community change and addressing locally‐determined goals in urban neighborhoods.
Characteristics of Oil from Seeds of 4 Mungbean [Vigna radiata (L.) Wilczek] Cultivars Grown in Pakistan
Authors: Zia‐Ul‐Haq Muhammad , Ahmad Mansoor , Iqbal Shahid
Published: July 2008

Mungbean is a widely consumed legume globally. This study was carried out for detailed characterization of oils from mungbean seeds from four indigenously cultivated varieties, as very little information is available on the oil composition of mungbean seeds and inter‐varietal variation in oil composition. The oil content was relatively low (2.1–2.7%). The investigated physiochemical parameters included refractive indices (RI) at 40 °C (1.4673–1.4698), relative density (0.9580–0.9618), iodine value (IV) (111.4 –117.1), saponification value (SV) (173.1–181.7 mg KOH/g) and unsaponifiable matter (UM) (13.8–15.01%). Phospholipids and triglycerides were the dominant lipid fractions followed by monoglycerides. Linoleic acid and oleic acid were the dominant fatty acids (FA). Characterization was also made by TLC. Tocopherol analysis demonstrated highest content of γ‐tocopherol among its isomers, while α‐tocotrienol was present in highest amount in all studied cultivars, among its isomers. Results from most of the parameters revealed significant (P ≤ 0.05) differences among the cultivars. The findings of the study reveal mungbean [Vigna radiata (L.) wilczek], to be a potentially valuable legume crop with comparable nutritional quality oil among all the cultivars.
Fatigue and Charting Errors: The Benefit of a Reduced Call Schedule
Authors: Warren Anna , Tart Rebecca Creech
Published: July 2008

THE EFFECTS OF FATIGUE caused by long work hours, working on call, and insufficient rest periods are often overlooked during reviews of perioperative documentation errors.

THE RELATIONSHIP BETWEEN fatigue and nurse charting errors prior to and after implementation of a reduced call schedule was examined at a not‐for‐profit, Magnet community hospital.

A SIGNIFICANT REDUCTION in nursing documentation errors was observed after the reduced call schedule was implemented, with the greatest reduction in errors seen among nurses working 12‐hour or call shifts. AORN J 88 (July 2008) 88–95. © AORN, Inc, 2008.
Effects of threatening information on interpersonal responses to pain
Authors: Jackson Todd , Huang Xiting , Chen Hong , Phillips Heath
Published: July 2008

Emerging evidence indicates that meanings attributed to pain contribute to tolerance and coping among affected individuals. However, links between pain appraisals and coping responses have received little attention within a broader interpersonal context. In this experiment, effects of appraisal on pain tolerance and coping were examined in adult dyads. Eighty‐six acquaintance/friend pairs were randomly assigned to the role of Participant in a cold pressor test (CPT) or observer–helper who assisted in coping. Before the task, pairs in the threat condition read about frostbite symptoms and consequences, while those in the reassurance condition read about the safety of the task. In a mixed condition, Participants and Observers read the reassurance and threat passage, respectively. Between‐groups analyses revealed threat group participants had lower pain tolerance and reported less cognitive coping than did participants in other appraisal conditions. Threat group observers reported less attention diversion, coping self‐statements and ignoring in helping their partner than did reassured observers. Pain language was also most prominent in transactions of threatened dyads. Finally, use of attention diversion by observers contributed to pain tolerance, independent of participant factors (reported pain, appraisal condition, reported coping) and pain language in conversations during immersions. The study highlights how appraisal contributes not only to pain tolerance and coping in the affected individual but also to care‐giving efforts of others in their social environment.
Diffusion tensor imaging in the developing human cerebellum with histologic correlation
Authors: Saksena Sona , Husain Nuzhat , Das Vinita , Pradhan Mandakani , Trivedi Richa , Srivastava Savita , Malik Gyanendra K. , Rathore Ram K.S. , Sarma Manoj , Pandey Chandra M. , Gupta Rakesh K.
Published: July 2008

Diffusion tensor imaging was performed on 24 freshly aborted human fetuses with gestational age ranging from 20 to 37 weeks to observe age‐related fractional anisotropy changes in cerebellar cortex and cerebellar white matter. Quantitative immunohistochemical analysis was performed for glial fibrillary acidic protein in each fetus molecular layer of cerebellar cortex and myelin basic protein expression was quantified in myelinated areas of the middle cerebellar peduncles. The cerebellar cortical fractional anisotropy reached its peak value at 28 weeks, and then decreased gradually until 37 weeks. The time course of glial fibrillary acidic protein expression paralleled that of fractional anisotropy in the cerebellar cortex from 20 weeks of gestation upto the gestational age at which the fractional anisotropy reached its peak value (28 weeks). In the middle cerebellar peduncles, the fractional anisotropy increased continuously upto 37 weeks of gestational age and showed a significant positive correlation with myelin basic protein immunostained fibers. The fractional anisotropy quantification can be used to assess the migrational and maturation changes during the development of the human fetal cerebellum supported by the immunohistochemical analysis.
Recurrent syncope associated with paroxysmal supraventricular tachycardia in a Devon Rex cat diagnosed by implantable loop recorder
Authors: Ferasin Luca
Published: July 2008

A 9-year-old male neutered Devon Rex cat was presented for continued investigations following a 7-year history of recurrent syncope. Previous diagnostic tests, including 24 h (Holter) electrocardiographic monitoring, had failed to identify the aetiology of such episodes, and former empirical treatment with atenolol had not provided satisfactory control of the clinical signs. A conclusive diagnosis was eventually achieved using an implantable loop recorder (Reveal), which identified paroxysmal supraventricular tachycardia (SVT) associated with a syncopal episode. Treatment with oral sotalol was instituted and, 18 months after initiation of anti-arrhythmic therapy, no further syncopal episodes have been observed by the cat's owners.
Evolution of a high-density electron beam in the field of a super-intense laser pulse
Authors: Kulagin V.V. , Cherepenin V.A. , Hur M.S. , Lee J. , Suk H.
Published: July 2008

The evolution of a high-density electron beam in the field of a super-intense laser pulse is considered. The one-dimensional (1D) theory for the description of interaction, taking into account the space-charge forces of the beam, is developed, and exact solutions for the equations of motion of the electrons are found. It was shown that the length of the high-density electron beam increases slowly in time after initial compression of the beam by the laser pulse as opposed to the low-density electron beam case, where the length is constant on average. Also, for the high-density electron beam, the sharp peak frozen into the density distribution can appear in addition to a microbunching, which is characteristic for a low-density electron beam in a super-intense laser field. Characteristic parameters for the evolution of the electron beam are calculated by an example of a step-like envelope of the laser pulse. Comparison with 1D particle-in-cell simulations shows adequacy of the derived theory. The considered issue is very important for a special two-pulse realization of a Thomson scattering scheme, where one high-intensity laser pulse is used for acceleration, compression and microbunching of the electron beam, and the other probe counter-streaming laser pulse is used for scattering with frequency up-shifting and amplitude enhancement.
Hantavirus disease (nephropathia epidemica) in Belgium: effects of tree seed production and climate
Authors: TERSAGO K. , VERHAGEN R. , SERVAIS A. , HEYMAN P. , DUCOFFRE G. , LEIRS H.
Published: July 2008

Recently, human cases of nephropathia epidemica (NE) due to Puumala virus infection in Europe have increased. Following the hypothesis that high reservoir host abundance induces higher transmission rates to humans, explanations for this altered epidemiology must be sought in factors that cause bank vole (Myodes glareolus) abundance peaks. In Western Europe, these abundance peaks are often related to high tree seed production, which is supposedly triggered by specific weather conditions. We evaluated the relationship between tree seed production, climate and NE incidence in Belgium and show that NE epidemics are indeed preceded by abundant tree seed production. Moreover, a direct link between climate and NE incidence is found. High summer and autumn temperatures, 2 years and 1 year respectively before NE occurrence, relate to high NE incidence. This enables early forecasting of NE outbreaks. Since future climate change scenarios predict higher temperatures in Europe, we should regard Puumala virus as an increasing health threat.
Outbreak of waterborne hepatitis E in Hyderabad, India, 2005
Authors: SAILAJA B. , MURHEKAR M. V. , HUTIN Y. J. , KURUVA S. , MURTHY S. P. , REDDY K. S. JOWAHER , RAO G. MASTAN , GUPTE M. D.
Published: July 2008

A large outbreak of hepatitis E occurred in 2005 in Hyderabad, Andhra Pradesh, India. A total of 1611 cases were reported between 1 March and 31 December 2005 (attack rate 40/100 000). The epidemic curve suggested a continuing common source outbreak. Cases were centred around open sewage drains that crossed the old city. The attack rate was significantly higher in neighbourhood blocks supplied by water supply lines that crossed open drains (203/100 000) than in blocks supplied by non-crossing water pipes with a linear trend (38/100 000, P<0·00001). Crossing water pipelines were repaired and the attack rates declined.
The transmission and control of XDR TB in South Africa: an operations research and mathematical modelling approach
Authors: BASU S. , GALVANI A. P.
Published: July 2008

Extensively drug-resistant tuberculosis (XDR TB) has emerged as a threat to TB control efforts in several high-burden areas, generating international concern. XDR TB is now found in every region of the world, but appears most worrisome in the context of HIV and in resource-limited settings with congregate hospital wards. Here, we examine the emergence and transmission dynamics of the disease, incorporating the mathematical modelling literature related to airborne infection and epidemiological studies related to the operations of TB control programmes in resource-limited settings. We find that while XDR TB may present many challenges in the setting of resource constraints, the central problems highlighted by the emergence of XDR TB are those that have plagued TB programmes for years. These include a slow rate of case detection that permits prolonged infectiousness, the threat of airborne infection in enclosed spaces, the problem of inadequate treatment delivery and treatment completion, and the need to develop health systems that can address the combination of TB and poverty. Mathematical models of TB transmission shed light on the idea that community-based therapy and rapid detection systems may be beneficial in resource-limited settings, while congregate hospital wards are sites for major structural reform.
Ten good reasons to consider biological processes in prevention and intervention research
Authors: Beauchaine Theodore P. , Neuhaus Emily , Brenner Sharon L. , Gatzke-Kopp Lisa
Published: July 2008

Most contemporary accounts of psychopathology acknowledge the importance of both biological and environmental influences on behavior. In developmental psychopathology, multiple etiological mechanisms for psychiatric disturbance are well recognized, including those operating at genetic, neurobiological, and environmental levels of analysis. However, neuroscientific principles are rarely considered in current approaches to prevention or intervention. In this article, we explain why a deeper understanding of the genetic and neural substrates of behavior is essential for the next generation of preventive interventions, and we outline 10 specific reasons why considering biological processes can improve treatment efficacy. Among these, we discuss (a) the role of biomarkers and endophenotypes in identifying those most in need of prevention; (b) implications for treatment of genetic and neural mechanisms of homotypic comorbidity, heterotypic comorbidity, and heterotypic continuity; (c) ways in which biological vulnerabilities moderate the effects of environmental experience; (d) situations in which Biology × Environment interactions account for more variance in key outcomes than main effects; and (e) sensitivity of neural systems, via epigenesis, programming, and neural plasticity, to environmental moderation across the life span. For each of the 10 reasons outlined we present an example from current literature and discuss critical implications for prevention.
Early behavioral intervention, brain plasticity, and the prevention of autism spectrum disorder
Authors: Dawson Geraldine
Published: July 2008

Advances in the fields of cognitive and affective developmental neuroscience, developmental psychopathology, neurobiology, genetics, and applied behavior analysis have contributed to a more optimistic outcome for individuals with autism spectrum disorder (ASD). These advances have led to new methods for early detection and more effective treatments. For the first time, prevention of ASD is plausible. Prevention will entail detecting infants at risk before the full syndrome is present and implementing treatments designed to alter the course of early behavioral and brain development. This article describes a developmental model of risk, risk processes, symptom emergence, and adaptation in ASD that offers a framework for understanding early brain plasticity in ASD and its role in prevention of the disorder.
Executive functions and school readiness intervention: Impact, moderation, and mediation in the Head Start REDI program
Authors: Bierman Karen L. , Nix Robert L. , Greenberg Mark T. , Blair Clancy , Domitrovich Celene E.
Published: July 2008

Despite their potentially central role in fostering school readiness, executive function (EF) skills have received little explicit attention in the design and evaluation of school readiness interventions for socioeconomically disadvantaged children. The present study examined a set of five EF measures in the context of a randomized-controlled trial of a research-based intervention integrated into Head Start programs (Head Start REDI). Three hundred fifty-six 4-year-old children (17% Hispanic, 25% African American; 54% girls) were followed over the course of the prekindergarten year. Initial EF predicted gains in cognitive and social–emotional skills and moderated the impact of the Head Start REDI intervention on some outcomes. The REDI intervention promoted gains on two EF measures, which partially mediated intervention effects on school readiness. We discuss the importance of further study of the neurobiological bases of school readiness, the implications for intervention design, and the value of incorporating markers of neurobiological processes into school readiness interventions.
Effects of early intervention on EEG power and coherence in previously institutionalized children in Romania
Authors: Marshall Peter J. , Reeb Bethany C. , Fox Nathan A. , Nelson Charles A. , Zeanah Charles H.
Published: July 2008

Two groups of Romanian children were compared on spectral power and coherence in the electroencephalogram (EEG) in early childhood. One group consisted of previously institutionalized children who had been randomly assigned to a foster care intervention at a mean age of 23 months. The second group had been randomized to remain in institutional care. Because of a policy of noninterference, a number of these children also experienced placement into alternative family care environments. There were minimal group differences between the foster care and institutionalized groups in EEG power and coherence across all measured frequency bands at 42 months of age. However, age at foster care placement within the foster care group was correlated with certain measures of EEG power and coherence. Earlier age at foster care placement was associated with increased alpha power and decreased short-distance EEG coherence. Further analyses separating age at placement from duration of intervention suggest that this effect may be more robust for EEG coherence than EEG band power. Supplementary analyses examined whether the EEG measures mediated changes in intellectual abilities within the foster care children, but no clear evidence of mediation was observed.
Biological processes in prevention and intervention: The promotion of self-regulation as a means of preventing school failure
Authors: Blair Clancy , Diamond Adele
Published: July 2008

This paper examines interrelations between biological and social influences on the development of self-regulation in young children and considers implications of these interrelations for the promotion of self-regulation and positive adaptation to school. Emotional development and processes of emotion regulation are seen as influencing and being influenced by the development of executive cognitive functions, including working memory, inhibitory control, and mental flexibility important for the effortful regulation of attention and behavior. Developing self-regulation is further understood to reflect an emerging balance between processes of emotional arousal and cognitive regulation. Early childhood educational programs that effectively link emotional and motivational arousal with activities designed to exercise and promote executive functions can be effective in enhancing self-regulation, school readiness, and school success.
Changes in the neural bases of emotion regulation associated with clinical improvement in children with behavior problems
Authors: Lewis Marc D. , Granic Isabela , Lamm Connie , Zelazo Philip David , Stieben Jim , Todd Rebecca M. , Moadab Ida , Pepler Debra
Published: July 2008

Children's behavior problems may stem from ineffective cortical mechanisms for regulating negative emotions, and the success of interventions may depend on their impact on such mechanisms. We examined neurophysiological markers associated with emotion regulation in children comorbid for externalizing and internalizing problems before and after treatment. We hypothesized that treatment success would correspond with reduced ventral prefrontal activation, and increased dorsomedial prefrontal activation, at the time point of an event-related potential (ERP) associated with inhibitory control. Twenty-seven 8- to 12-year-old children (with usable data) were tested before and after a 14-week community-based treatment program and assessed as to improvement status. Fifteen 8- to 12-year-olds from the normal population (with usable data) were tested over the same interval. All children completed an emotion-induction go/no-go task while fitted with a 128-channel electrode net at each test session. ERP amplitudes, and estimates of cortical activation in prefrontal regions of interest, were measured at the peak of the “inhibitory” N2 and compared between improvers, nonimprovers, and nonclinical children. ERP amplitudes showed no group differences. However, improvers showed an overall reduction in ventral prefrontal activation from pretreatment to posttreatment, bringing them in line with nonclinical children, whereas ventral activation remained high for nonimprovers. Both improvers and nonimprovers showed high dorsal activation relative to nonclinical children. Supplementary analyses indicated that only ventral prefrontal regions, and only within the N2 time window, showed decreased activity from pre- to posttreatment, suggesting changes in regulatory processes rather than in overall emotional arousal. These cortically mediated changes may permit a reduction in the overengaged, rigid style of emotion regulation characteristic of children with behavior problems.
Intervention effects on foster parent stress: Associations with child cortisol levels
Authors: Fisher Philip A. , Stoolmiller Mike
Published: July 2008

Foster children exhibit high rates of atypical neuroendocrine functioning compared to children in the general population. In particular, alterations in the daytime diurnal activity of the hypothalamic–pituitary–adrenal (HPA) axis have been observed in foster children, often characterized by blunted salivary cortisol levels (i.e., low morning levels that remain low throughout the day). There is emerging evidence that therapeutic interventions for foster children can affect this pattern of HPA axis activity, but the specific intervention components responsible for change have not been fully explicated. Within a randomized trial to evaluate a therapeutic intervention for foster preschoolers (n= 57 intervention condition;n= 60 comparison condition;n= 60 community comparison condition), the present study examined whether diurnal cortisol activity was associated with caregiver self-reported stress in response to child problem behavior. Results showed immediate reductions in caregiver stress that were sustained through 12 months postbaseline in the intervention condition. In contrast, caregivers in the regular foster care condition showed higher rates of stress across time and increased stress sensitivity to child problem behaviors. In addition, among caregivers in regular foster care, higher self-reported stress was associated with lower morning cortisol levels and more blunted diurnal cortisol activity. These results provide evidence that interventions can simultaneously impact caregiver stress and buffer children from the negative impacts of caregiver stress on HPA axis regulation.
Adhesion molecules in the regulation of CNS myelination
Authors: Laursen Lisbeth S. , Ffrench-Constant Charles
Published: July 2008

Myelination is necessary both for rapid salutatory conduction and the long-term survival of the axon. In the CNS the myelin sheath is formed by the oligodendrocytes. Each oligodendrocyte myelinates several axons and, as the number of wraps around each axon is determined precisely by the axon diameter, this requires a close, highly regulated interaction between the axons and each of the oligodendrocyte processes. Adhesion molecules are likely to play an important role in the bi-directional signalling between axon and oligodendrocyte that underlies this interaction. Here we review the current knowledge of the function of adhesion molecules in the different phases of oligodendrocyte differentiation and myelination, and discuss how the properties of these proteins defined by other cell biological systems indicates potential roles in oligodendrocytes. We show how the function of a number of different adhesion and cell–cell interaction molecules such as polysialic acid neural cell adhesion molecule, Lingo-1, Notch, neuregulin, integrins and extracellullar matrix proteins provide negative and positive signals that coordinate the formation of the myelin membrane. Compiling this information from a number of different cell biological and genetic experiments helps us to understand the pathology of multiple sclerosis and direct new areas of research that might eventually lead to potential drug targets to increase remyelination.
MHD simulations of the global solar corona around the Halloween event in 2003 using the synchronic frame format of the solar photospheric magnetic field
Authors: Hayashi Keiji , Zhao Xue Pu , Liu Yang
Published: July 2008

We performed two time‐relaxation magnetohydrodynamics (MHD) simulations of the solar corona: one uses the boundary map representing the solar surface magnetic field distribution before the Halloween event in 2003, and the other uses map representing the postevent distribution. The aims of this study are to test a new concept of a solar surface magnetic field map capable of representing a particular time of interest and to examine the coronal responses to the solar photospheric magnetic field changes occurring over a few days. We used a new mapping scheme named “synchronic frame” that can include the longitudinal shift caused by the solar differential rotation and the solar surface variations occurring at the time of interest. These two time‐relaxation MHD simulations using the two maps are separately performed to numerically obtain the quasi steady states of the solar corona before and after the Halloween event. Comparisons of the simulated coronal magnetic field structures to the SOHO/EIT measurements show that the combinations of our mapping method and simulation model reproduce the changes of the coronal structures well. We also find that the consequences of solar surface variations can be seen in the plasma quantities in the solar corona. These results show the capability and importance of the solar surface magnetic field mapping scheme for better reconstruction of global coronal structures, parts of which are sensitive to the solar surface magnetic field variations.
Decreases in atomic hydrogen over the summer pole: Evidence for dehydration from polar mesospheric clouds?
Authors: Siskind David E. , Marsh Daniel R. , Mlynczak Martin G. , Martin‐Torres F. Javier , Russell James M.
Published: July 2008

Observations from the Sounding of the Atmosphere with Broadband Emission Radiometry (SABER) instrument on the NASA/Thermospheric Ionosphere Mesosphere Energetics and Dynamics satellite show a surprising decrease in the inferred atomic hydrogen (H) over the polar regions in the lowermost thermosphere during the summer. This contrasts with predictions by global models that H should peak in this region at this time. We suggest the decrease is a consequence of the sequestering of the water vapor by the formation of polar mesospheric clouds (PMCs) that redistributes the H2O thus reducing the chemical source of H. This decrease is more pronounced in the Northern rather than the Southern summer which is roughly consistent with the known morphology of PMCs. A model calculation which includes a PMC parameterization gives good qualitative agreement with the data suggesting that this process should be considered in global models of the coupling between the middle and upper atmosphere.
Estimating the efficiency of benzodiazepines on GABAAreceptors comprising γ1 or γ2 subunits
Authors: Baburin I , Khom S , Timin E , Hohaus A , Sieghart W , Hering S
Published: July 2008

Background and purpose:

Heterologous expression of α1, β2 and γ2S(γ1) subunits produces a mixed population of GABAAreceptors containing α1β2 or α1β2γ2S(γ1) subunits. GABA sensitivity (lower in receptors containing γ1 or γ2S subunits) and the potentiation of GABA‐activated chloride currents (IGABA) by benzodiazepines (BZDs) are dependent on γ2S(γ1) incorporation. A variable γ subunit incorporation may affect the estimation ofIGABApotentiation by BZDs. We propose an approach for estimation of BZD efficiency that accounts for mixed population of α1β2 and α1β2γ2S(γ1) receptors.

Experimental approach:

We investigated the relation between GABA sensitivity (EC50) and BZD modulation by analysing triazolam‐, clotiazepam‐ and midazolam‐induced potentiation ofIGABAinXenopusoocytes under two‐microelectrode voltage clamp.

Key results:

PlottingEC50versus BZD‐induced shifts of GABA concentration‐response curves (ΔEC50(BZD)) of oocytes injected with different amounts of α1, β2 and γ2S(γ1) cRNA (1:1:1–1:1:10) revealed a linear regression between γ2S(γ1)‐mediated reduction of GABA sensitivity (EC50) and ΔEC50(BZD). The slope factors of the regression were always higher for oocytes expressing α1β2γ1 subunit receptors (1.8±0.1 (triazolam), 1.6±0.1 (clotiazepam), 2.3±0.2 (midazolam)) than for oocytes expressing α1β2γ2S receptors (1.4±0.1 (triazolam), 1.4±0.1 (clotiazepam), 1.3±0.1 (midazolam)). Mutant GABAAreceptors (α1β2‐R207Cγ2S) with lower GABA sensitivity showed higher drug efficiencies (slope factors=1.1±0.1 (triazolam), 1.1±0.1 (clotiazepam), 1.2±0.1 (midazolam)).

Conclusions and implications:

Regression analysis enabled the estimation of BZD efficiency when variable mixtures of α1β2 and α1β2γ2S(γ1) receptors are expressed and provided new insights into the γ2S(γ1) dependency of BZD action.

British Journal of Pharmacology(2008)155, 424–433; doi:10.1038/bjp.2008.271; published online 7 July 2008
Investigation of the role of 5‐HT2receptor subtypes in the control of the bladder and the urethra in the anaesthetized female rat
Authors: Mbaki Y , Ramage A G
Published: July 2008

Background and purpose:

Micturition is controlled by central 5‐HT‐containing pathways. 5‐HT2receptors have been implicated in this system especially in control of the urethra, which is a drug target for treating urinary incontinence. This study investigates the role of each of the three subtypes of this receptor with emphasis on sphincter regulation.

Experimental approach:

Recordings of urethral and bladder pressure, external urethral sphincter (EUS) EMG, as well as the micturition reflex induced by bladder distension along with blood pressure and heart rate were made in anaesthetized rats. The effects of agonists and antagonists for 5‐HT2receptor subtypes were studied on these variables.

Key results:

The 5‐HT2Cagonists Ro 60‐0175, WAY 161503 and mCPP, i.v., activated the EUS, increased urethral pressure and inhibited the micturition reflex. The effects of Ro 60‐0175 on the EUS were blocked by the 5‐HT2Cantagonist SB 242084 and the 5‐HT2Aantagonists, ketanserin and MDL 100907. SB 242084 also blocked the inhibitory action on the reflex, while the 5‐HT2Bantagonist RS 127445 only blocked the increase in urethral pressure. The 5‐HT2Areceptor agonist DOI given i.v. or i.t. but not i.c.v. activated the EUS.

Conclusions and implications:

5‐HT2A/2Creceptors located in the sacral spinal cord activate the EUS, while central 5‐HT2Creceptors inhibit the micturition reflex and 5‐HT2Breceptors, probably at the level of the urethra, increase urethral smooth muscle tone. Furthermore, 5‐HT2Band 5‐HT2Creceptors do not seem to play an important role in the physiological regulation of micturition.

British Journal of Pharmacology(2008)155, 343–356; doi:10.1038/bjp.2008.273; published online 7 July 2008
Literature‐based evaluation of four ‘hard endpoint’ models for assessing drug‐induced torsades de pointes liability
Authors: Vos M A
Published: July 2008

In safety pharmacology, a number of preclinical models for detecting drug‐induced proarrhythmia liability have been recently introduced that utilize hard endpoints: early after depolarziations (EADs), torsades de pointes (TdP) or both as the principal biomarker. To explore the validity of four of the most common of these models, (the isolated canine/rabbit left ventricular wedge preparation, the isolated rabbit heart, the methoxamine‐pretreated anaesthetized rabbit and the complete, chronic AV‐blocked (CAVB) dog (conscious and anaesthetized), the present article reviews published data sets for three drugs with recognized and different human TdP liabilities (cisparide, terfenadine and moxifloxacinin). Finally, this review considers the value of inclusion of analysis of beat‐to‐beat variability of repolarization (BVR) in TdP liability testing to improve sensitivity and specificity.

British Journal of Pharmacology(2008)154, 1523–1527; doi:fn1; published online 7 July 2008
α2‐Adrenoceptor action on cell proliferation and mammary tumour growth in mice
Authors: Bruzzone A , Piñero C Pérez , Castillo L F , Sarappa M G , Rojas P , Lanari C , Lüthy I A
Published: July 2008

Background and purpose:

Breast cancer, the most common cancer in women in most countries, is a highly stressful disease. Catecholamines released during stress bind to adrenoceptors and we have recently described α2‐adrenoceptors in human breast cell lines, linked to enhanced cell proliferation. The purpose was to assess thein vivoeffects of compounds acting on α2‐adrenoceptors in a reliable model of breast cancer.

Experimental approach:

The expression of α2‐adrenoceptors was confirmed by immunocytochemistry, immunofluorescence and reverse transcription‐PCR in the mouse mammary tumour cell line MC4‐L5. Proliferation was assessed by [3H]thymidine incorporation and tumours were measured daily. Apoptosis was assessed by terminal deoxynucleotidyl transferase‐mediated dUTP digoxigenin nick‐end labelling.

Key results:

Incubation for 2 days with α2‐adrenoceptor agonists (clonidine and dexmedetomidine) significantly enhanced proliferation of the mouse mammary tumour cell line MC4‐L5. These agonists also significantly stimulated tumour growth of the progestin‐dependent tumour C4‐HD even in the presence of medroxyprogesterone acetate (MPA). In every tumour tested (C4‐HD, CC4‐2‐HD and CC4‐3‐HI), regardless of MPA sensitivity, clonidine significantly enhanced tumour growth in the absence of MPA. The α2‐adrenoceptor antagonists, yohimbine and rauwolscine, completely reversed the effects of clonidine. However, the group receiving yohimbine alone showed a nonsignificant but constant increase in tumour growth, whereas rauwolscine alone diminished tumour growth significantly, behaving as a reverse agonist. In CC4‐3‐HI tumours, rauwolscine treatment enhanced apoptosis and diminished the mitotic index, whereas clonidine had the inverse effect.

Conclusions and implications:

α2‐Adrenoceptor agonists enhanced tumour growth and rauwolscine behavedin vivoas a reverse agonist, suggesting that it may be tested for adjuvant treatment.

British Journal of Pharmacology(2008)155, 494–504; doi:10.1038/bjp.2008.278; published online 7 July 2008
Novel long‐acting bronchodilators for COPD and asthma
Authors: Cazzola M , Matera M G
Published: July 2008

An important step in simplifying asthma and chronic obstructive pulmonary disease (COPD) management and improving adherence with prescribed therapy is to reduce the dose frequency to the minimum necessary to maintain disease control. Therefore, the incorporation of once‐daily dose administration is an important strategy to improve adherence and is a regimen preferred by most patients, which may also lead to enhancement of compliance, and may have advantages leading to improved overall clinical outcomes. Once‐daily β2‐agonists or ultra long‐acting β2‐agonists (LABAs) such as carmoterol, indacaterol, GSK‐159797, GSK‐597901, GSK‐159802, GSK‐642444 and GSK‐678007 are under development for the treatment of asthma and COPD. Also some new long‐acting antimuscarinic agents (LAMAs) such as aclidinium, LAS‐35201, GSK656398, GSK233705, NVA‐237 (glycopyrrolate) and OrM3 are under development. In any case, the current opinion is that it will be advantageous to develop inhalers containing combination of several classes of long‐acting bronchodilator drugs in an attempt to simplify treatment regimens as much as possible. Consequently, several options for once‐daily dual‐action ultra LABA+LAMA combination products are currently being evaluated. A different approach is to have a dimer molecule in which both pharmacologies are present (these molecules are known as M3 antagonist‐β2 agonist (MABA) bronchodilators). The advent of a successful MABA product will revolutionize the field and open the door for a new range of combination products.

British Journal of Pharmacology (2008) 155, 291–299; doi:10.1038/bjp.2008.284; published online 7 July 2008
Bradykinin regulates human colonic ion transport in vitro
Authors: Baird A W , Skelly M M , O'Donoghue D P , Barrett K E , Keely S J
Published: July 2008

Background and purpose:

Kinins are acknowledged as important regulators of intestinal function during inflammation; however, their effects on human intestinal ion transport have not been reported. Here, we used muscle‐stripped human colonic tissue and cultured T84‐cell monolayers to study bradykinin (BK) actions on human intestinal ion transport.

Experimental approach:

Ion transport was measured as changes in short‐circuit current (Isc) across colonic epithelia mounted in Ussing chambers.

Key results:

In intact tissue, there was a distinct polarity to BK‐elicited Isc responses. Whereas basolateral BK stimulated sustained responses (EC50=0.5±0.1 μM), those to apical BK were more rapid and transient (EC50=4.1±1.2 nM). In T84 cells, responses to both apical and basolateral BK were similar to those seen upon apical addition to intact tissues. Cross‐desensitization between apical and basolateral domains was not observed. BK‐induced responses were largely due to Cl− secretion as shown by their sensitivity to bumetanide and removal of Cl− from the bathing solution. Studies using selective agonists and antagonists indicate responses to BK are mediated by B2 receptors. Finally, responses to basolateral BK in intact tissues were inhibited by tetrodotoxin (1 μM), atropine (1 μM), capsaicin (100 μM) and piroxicam (10 μM). BK‐stimulated prostaglandin (PG)E2 release from colonic tissue.

Conclusions:

BK stimulates human colonic Cl− secretion by activation of apical and basolateral B2 receptors. Responses to apical BK reflect a direct action on epithelial cells, whereas those to basolateral BK are amplified by stimulation of enteric nerves and PG synthesis.

British Journal of Pharmacology (2008) 155, 558–566; doi:10.1038/bjp.2008.288; published online 7 July 2008
Ypp1/YGR198w plays an essential role in phosphoinositide signalling at the plasma membrane
Authors: Zhai Chao , Li Kuoyu , Markaki Valentini , Phelan John P. , Bowers Katherine , Cooke Frank T. , Panaretou Barry
Published: July 2008

Phosphoinositide signalling through the eukaryotic plasma membrane makes essential contributions to many processes, including remodelling of the actin cytoskeleton, vesicle trafficking and signalling from the cell surface. A proteome-wide screen performed in Saccharomyces cerevisiae revealed that Ypp1 interacts physically with the plasma-membrane-associated phosphoinositide 4-kinase, Stt4. In the present study, we demonstrate that phenotypes of ypp1 and stt4 conditional mutants are identical, namely osmoremedial temperature sensitivity, hypersensitivity to cell wall destabilizers and defective organization of actin. We go on to show that overexpression of STT4 suppresses the temperature-sensitive growth defect of ypp1 mutants. In contrast, overexpression of genes encoding the other two phosphoinositide 4-kinases in yeast, Pik1 and Lsb6, do not suppress this phenotype. This implies a role for Ypp1 in Stt4-dependent events at the plasma membrane, as opposed to a general role in overall metabolism of phosphatidylinositol 4-phosphate. Use of a pleckstrin homology domain sensor reveals that there are substantially fewer plasma-membrane-associated 4-phosphorylated phosphoinositides in ypp1 mutants in comparison with wild-type cells. Furthermore, in vivo labelling with [3H]inositol indicates a dramatic reduction in the level of phosphatidylinositol 4-phosphate in ypp1 mutants. This is the principal cause of lethality under non-permissive conditions in ypp1 mutants, as limiting the activity of the Sac1 phosphoinositide 4-phosphate phosphatase leads to restoration of viability. Additionally, the endocytic defect associated with elevated levels of PtdIns4P in sac1Δ cells is restored in combination with a ypp1 mutant, consistent with the opposing effects that these two mutations have on levels of this phosphoinositide.
An exceptional salt-tolerant antimicrobial peptide derived from a novel gene family of haemocytes of the marine invertebrate Ciona intestinalis
Authors: Fedders Henning , Michalek Matthias , Grötzinger Joachim , Leippe Matthias
Published: July 2008

A novel gene family coding for putative antimicrobial peptides was identified in the EST (expressed sequence tag) database of the sea squirt Ciona intestinalis, and one of these genes was molecularly cloned from the Northern European Ciona subspecies. In situ hybridization and immunocytochemical analysis revealed that the natural peptide is synthesized and stored in a distinct haemocyte type, the univacuolar non-refractile granulocytes. By semiquantitative RT–PCR (reverse transcription–PCR) analysis, it was shown that the expression of the gene is markedly up-regulated in haemocytes after immune challenge. To evaluate the antimicrobial potency of the putative defence protein, we synthesized a peptide corresponding to its cationic core region. The peptide was highly effective against Gram-negative and Gram-positive bacteria including several human and marine pathogens as well as the yeast Candida albicans. Notably, the antibacterial activity of the peptide was retained at salt concentrations of up to 450 mM NaCl. Using two different methods we demonstrated that the peptide kills Gram-negative and Gram-positive bacteria by permeabilizing their cytoplasmic membranes. CD spectroscopy revealed that, in the presence of liposomes composed of negatively charged phospholipids, the peptide undergoes a conformational change and adopts an α-helical structure. Moreover, the peptide was virtually non-cytolytic for mammalian erythrocytes. Hence, the designed salt-tolerant antimicrobial peptide may represent a valuable template for the development of novel antibiotics.
The finite harmonic oscillator and its associated sequences
Authors: Gurevich Shamgar , Hadani Ronny , Sochen Nir
Published: July 2008

A system of functions (signals) on the finite line, called the oscillator system, is described and studied. Applications of this system for discrete radar and digital communication theory are explained.
The neurobiology of pathological gambling and drug addiction: an overview and new findings
Authors: Potenza Marc N
Published: July 2008

Gambling is a prevalent recreational behaviour. Approximately 5% of adults have been estimated to experience problems with gambling. The most severe form of gambling, pathological gambling (PG), is recognized as a mental health condition. Two alternate non-mutually exclusive conceptualizations of PG have considered it as an obsessive-compulsive spectrum disorder and a ‘behavioural’ addiction. The most appropriate conceptualization of PG has important theoretical and practical implications. Data suggest a closer relationship between PG and substance use disorders than exists between PG and obsessive-compulsive disorder. This paper will review data on the neurobiology of PG, consider its conceptualization as a behavioural addiction, discuss impulsivity as an underlying construct, and present new brain imaging findings investigating the neural correlates of craving states in PG as compared to those in cocaine dependence. Implications for prevention and treatment strategies will be discussed.