bluuebunny/crossref_metadata_2025 huggingface dataset:
Canonicial Transformations and the Hamilton‐Jacobi Theorem in the Optimum Control Theory
Authors: Djukić Djordje S. , Vujanović Bozidar D.
Published: June 2007

This paper deals with the problem to establish a profound relationship between Pontryagin's maximum principle and Bellman's dynamic programming method via the canonical transformations of the variables, as it is a case in classical mechanics. A rigorous form of the Hamilton‐Jacobi theorem is proved for optimal control systems. Further it is shown that the controlled systems may be treated by a partial differential equation of the Hamilton‐Jacobi type, which, however, is fundamentally different of the Bellman functional equation. The solution of this equation is a function of the generalized momenta, which appear in Pontryagin's theory, and the time. In some cases this equation can be advantageously used in comparison with the Bellman equation. An example is solved to illustrate the presented theory.
Streamlining progress-based derivations of concurrent programs
Authors: Dongol Brijesh , Mooij Arjan J.
Published: June 2007

The logic of Owicki and Gries is a well-known logic for verifying safety properties of concurrent programs. Using this logic, Feijen and van Gasteren describe a method for deriving concurrent programs based on safety. In this work, we explore derivation techniques of concurrent programs using progress-based reasoning. We use a framework that combines the safety logic of Owicki and Gries, and the progress logic of UNITY. Our contributions improve the applicability of our earlier techniques by reducing the calculational overhead in the formal proofs and derivations. To demonstrate the effectiveness of our techniques, a derivation of Dekker’s mutual exclusion algorithm is presented. This derivation leads to the discovery of some new and simpler variants of this famous algorithm.
Mitochondrial Neurogastrointestinal Encephalomyopathy (MNGIE): Biochemical Features and Therapeutic Approaches
Authors: Lara M. C. , Valentino M. L. , Torres-Torronteras J. , Hirano M. , Martí R.
Published: June 2007

Over the last 15 years, important research has expanded our knowledge of the clinical, molecular genetic, and biochemical features of mitochondrial neurogastrointestinal encephalomyopathy (MNGIE). The characterization of mitochondrial involvement in this disorder and the seminal determination of its genetic cause, have opened new possibilities for more detailed and deeper studies on the pathomechanisms in this progressive and fatal disease. It has been established that MNGIE is caused by mutations in the gene encoding thymidine phosphorylase (TP), which lead to absolute or nearly complete loss of its catalytic activity, producing systemic accumulations of its substrates, thymidine (dThd) and deoxyuridine (dUrd). Findings obtained from in vitro and in vivo studies indicate that the biochemical imbalances specifically impair mitochondrial DNA (mtDNA) replication, repair, or both leading to mitochondrial dysfunction. We have proposed that therapy for MNGIE should be aimed at reducing the concentrations of these toxic nucleosides to normal or nearly normal levels. The first treatment, allogeneic stem-cell transplantation (alloSCT) reported in 2006, produced a nearly full biochemical correction of the dThd and dUrd imbalances in blood. Clinical follow-up of this and other patients receiving alloSCT is necessary to determine whether this and other therapies based on a permanent restoration of TP will be effective treatment for MNGIE.
Ontogeny of cocaine‐ and amphetamine‐regulated transcript (CART) peptide and calbindin immunoreactivity in granule cells of the dentate gyrus in the rat
Authors: Ábrahám Hajnalka , Orsi Gergely , Seress László
Published: June 2007

Cocaine‐ and amphetamine‐regulated transcript (CART) peptide was first discovered in the rat striatum following cocaine and amphetamine administration. However, even without psychostimulant treatment, many neuronal groups of the central nervous system, including granule cells of the dentate gyrus, express CART peptide. Earlier studies, based on the prenatal expression of CART peptide in the mesencephalon, suggest that it exerts neurotrophic effects. In the present study, ontogenetic expression of CART peptide in dentate gyrus granule cells was studied using immunohistochemistry in rats from 5 days to 3 months old. Expression was correlated with the expression of another neurochemical marker of granule cells, the calcium binding protein, calbindin.

Calbindin was already present in granule cells at postnatal day 5 (P5), whereas CART peptide was first observed at P12. The first CART peptide‐ and calbindin‐immunoreactive cells were localized to the lateral end of the dorsal blade, to the outer part of granule cell layer adjacent to the molecular layer, which agrees with the localization of the first‐generated granule cells in the dentate gyrus. The first calbindin‐immnunoreactive mossy fibers were seen at P9 in the stratum lucidum of CA3, and the entire projection path of mossy fibers expressed calbindin at P18. Mossy fibers were CART peptide‐immunopositive at P12, and they were visible in the most distal part of CA3, in CA3a next to CA2. This localization fits with the known spatial organization of mossy fiber axon terminals. An adult‐like expression of CART peptide and calbindin in the hippocampal formation was detectable at P30.

The late postnatal appearance of CART peptide in dentate granule cells, and their axonal terminals, indicates that CART peptide may play a neurotrophic role in late developmental events, such as synaptogenesis. However, this does not exclude the possibility of a neuromodulatory role for this peptide.
Job demands and dementia risk among male twin pairs
Authors: Potter Guy G. , Helms Michael J. , Burke James R. , Steffens David C. , Plassman Brenda L.
Published: June 2007

Background

Job characteristics may influence risk of dementia, but some types of job complexity remain to be examined. Twin studies provide a useful methodology for examining job differences between pairs who share many environmental and genetic influences.

Methods

Members of the National Academy of Sciences‐National Research Council's Twins Registry of World War II Veterans received a clinical evaluation for dementia and job ratings from the Dictionary of Occupational Titles.

Results

Co‐twin control models (n = 220 pairs) indicated lower risk of dementia with greater job demands of reasoning, mathematics, language, and vocational training, with comparable results in case‐control models (n = 425 cases). These effects were significant among twin pairs discordant for ≥6 years, but not among those discordant between 3–5 years. Results were similar for Alzheimer's disease, and the main effects were not further explained by zygosity or apolipoprotein E genotype.

Conclusions

Jobs that utilize data, academic skills, and extensive vocational training may protect against dementia. However, in twin pairs, these effects only emerged among individuals who remained free of dementia several years after onset in their sibling.
A chapter in the development of Alzheimer's disease research: A case study of public policies on the development and funding of research programs
Authors: Khachaturian Zaven S.
Published: June 2007

Although Alzheimer's disease, as a clinical‐neuropathologic entity, was described 100 years ago by Alois Alzheimer, the preponderance of knowledge about the disease has accumulated since the 1970s. The dramatic advances in research during the last three decades propelled the disease from near obscurity to the forefront of modern biomedical science. The remarkable transformation of this field of study is reflected by the exponential increase in the number of investigators, publications, and funded projects. The current preeminence of dementia research is largely due to the increasing numbers and quality of significant breakthroughs in understanding the molecular neurobiology of the disease. Multiple promising leads have created an atmosphere of optimism about the prospects of discovering effective interventions to delay the progression of the disease. Some of the key factors that influenced the pace of progress and helped to change the “status” of dementia research were: a) increases in research funding, b) recruitment of new scientific talent, with a convergence of know‐how and technologies, c) several crucial discoveries in molecular neurobiology, and d) National Institute on Aging initiatives to promote interdisciplinary research programs by creating a nationwide network of collaborating investigators and a research infrastructure/resource. This is an account of how the evolution of research into Alzheimer's disease occurred: a story about the critical findings, people, and public policies that influenced the amazing progress in understanding the underlying molecular mechanisms of the disease and in setting the stage for the discovery of a cure.
Commentary on “Health economics and the value of therapy in Alzheimer's disease.” Value therapy for Alzheimer's disease—A European perspective
Authors: Vellas Bruno , Froelich Lutz , Sampaio C.
Published: June 2007

The overall goal of value therapy is to provide the most efficient use of resources, taking into account both the cost and the value derived from a given technology or drug, and to assist in healthcare decision‐making, because both cost and effectiveness are considered. After a short review of European Medicines Agency (EMEA) Committee for Medicinal Products for Human Use (CHMP) recommendations for the development of medications for Alzheimer's disease, we focus on the evidence with respect to cost and benefits obtained so far with acetylcholinesterase inhibitor (AChEI) and Memantine in the treatment of Alzheimer's disease. We then analyze the recommendations developed by professionals for the treatment of Alzheimer's disease at the national level in European countries, and finally we discuss how to utilize this process more homogenously in the future to assess value therapeutic values in Alzheimer's disease.
In‐home monitoring of persons with dementia: Ethical guidelines for technology research and development
Authors: Mahoney Diane F. , Purtilo Ruth B. , Webbe Frank M. , Alwan Majd , Bharucha Ashok J. , Adlam Tim D. , Jimison Holly B. , Turner Beverly , Becker S. Ann ,   Working Group on Technology of the Alzheimer's Association
Published: June 2007

Innovative technologies are rapidly emerging that offer caregivers the support and means to assist older adults with cognitive impairment to continue living “at home.” Technology research and development efforts applied to older adults with dementia invoke special grant review and institutional review board concerns, to ensure not only safe but also ethically appropriate interventions. Evidence is emerging, however, that tensions are growing between innovators and reviewers. Reviewers with antitechnology biases are in a position to stifle needed innovation. Technology developers who fail to understand the clinical and caregiving aspects of dementia may design applications that are not in alignment with users' capabilities. To bridge this divide, we offer an analysis of the ethical issues surrounding home monitoring, a model framework, and ethical guidelines for technology research and development for persons with Alzheimer's disease and their caregivers.
Peripheral Primitive Neuroectodermal Tumour of the Hand in an Adult
Authors: JAYAKUMAR S. , JATAVALABULLA S. , MILLER I. M.
Published: June 2007

We present a case of a 28 year-old woman who presented with a peripheral primitive neuroectodermal tumour of the right hand involving the fifth metacarpal and little finger. She underwent excision biopsy, then ray amputation of her right little finger. Initial radiological staging did not reveal metastasis but, after recurrence locally at two years and in spite of adjuvant chemotherapy and radiotherapy, the patient died of progressive metastatic disease 4 years later. The current concepts and difficulties in diagnosing these tumours are discussed.
Is Complete Release of all Volar Carpal Canal Structures Necessary for Complete Decompression in Endoscopic Carpal Tunnel Release?
Authors: YOSHIDA A. , OKUTSU I. , HAMANAKA I.
Published: June 2007

This study investigated the need to completely divide the flexor retinaculum to achieve full decompression of the median nerve in the carpal canal, using carpal canal pressure measurements at the mid-point and/or the proximal one-third of the flexor retinaculum to analyse the degree of decompression after release of successive lengths of the flexor retinaculum from the distal holdfast fibres to its proximal margin. Pressure measurements were taken at each operative step in the resting hand position and during active power gripping. The pressure measurements indicated that decompression of the carpal canal was achieved both at rest and on active gripping after complete division of the flexor retinaculum. However, pressure measurements indicated that complete decompression had not been achieved during active power gripping with the proximal one-third of the flexor retinaculum intact. These results demonstrate the need for complete release of the full length of the flexor retinaculum, including the distal holdfast fibres.
Supply chain integration and shareholder value: Evidence from consortium based industry exchanges
Authors: Mitra Sabyasachi , Singhal Vinod
Published: June 2007

Recent trade and academic literature point to the importance of supply chain integration among partners as a key determinant of value creation. This paper analyzes the shareholder value effects of setting up industry exchanges, a prominent mechanism used to achieve supply chain integration. Shareholder value effects are estimated by measuring the stock market reaction (abnormal returns) associated with announcements to form or join industry exchanges. We find that abnormal returns from participation in industry exchanges are positive but only marginally significant in the whole sample of 144 firms in 18 exchanges formed during 2000–2001. In the sub‐sample of 88 exchange founders who were part of the original announcements to form the exchange, the abnormal market reaction is about 1% and significant. We also find that firms with greater bargaining power and higher process efficiency benefit more from participation in industry exchanges.
Talking about composing in secondary school music lessons
Authors: Major Angela E.
Published: June 2007

This paper reports an action research study of teacher and pupil talk about composing. Data were collected through video and audio recordings of composition lessons in a secondary school. Qualitative analysis of the data led to the development of a ‘typology of pupil talk about composing’ which distinguishes between six main types: exploration, description, opinion, affective response, evaluation and problem solving. The results of the study suggest that as children engage and empathise affectively and acquire ownership of their work, they appear to be able to talk more confidently about it. As children make sense of their work, they may well be able to understand more than their talk reveals. The role of teachers in nurturing talk about composing work in the classroom is considered in relation to the findings. By designing appropriate composing tasks, they may be able to promote the development of more mature forms of evaluative talk in younger children, and of their critical listening and appraising skills. The development of more mature, ‘higher’ forms of evaluative talk in younger children might be promoted by teachers in designing composing tasks.
Cultural Heritage Legislation and Management in Nigeria
Authors: Shyllon Folarin
Published: June 2007

Cultural heritage legislation and management commenced in Nigeria seventy years ago. Nonetheless, the Nigerian commission for museums and monuments remains a marginal institution without adequate resources to manage and protect the country's cultural heritage. The consolidating legislation of 1979 was hurriedly enacted and has many defects. The sanctions and protective measures enshrined in the Act are now hopelessly inadequate. In short, the legislation is in need of urgent revision and re-enactment. The cultural heritage managers need to evince a greater commitment and a higher sense of probity than hitherto in order to have a comprehensive cultural heritage management programme for the country. Cultural heritage management in Nigeria today is neither well organized nor co-ordinated. The authorities must appreciate that cultural heritage management has an ideological basis, which is sustaining the cultural identity of a people.
An empirical study of climatic controls on riverine C export from three major U.S. watersheds
Authors: Raymond Peter A. , Oh Neung‐Hwan
Published: June 2007

The correlations between annual precipitation, evaporation, temperature, and annual carbon export (bicarbonate, dissolved organic carbon, and particulate organic carbon) are established for the Ohio, upper Mississippi, and Missouri watersheds and coefficients that predict C export on the basis of precipitation, evapotranspiration, and seasonal temperature are provided. Interannual variation in carbon export is controlled by the level of precipitation and evapotranspiration, the discharge to precipitation ratio (D:P), the concentration of the major carbon pool, the rating curve (discharge versus carbon concentration plots), and seasonal temperature. Within a watershed, precipitation has the strongest correlation with annual carbon export for all carbon pools. In the upper Mississippi and Ohio, levels of evapotranspiration can predict the majority of the residuals of precipitation versus carbon export. Bicarbonate demonstrates the largest response in yield to annual precipitation variation for each watershed. Rating curves, however, indicate that dissolved organic carbon and particulate organic carbon generally increase with increasing discharge, while bicarbonate decreases, causing a larger percentage response to precipitation for the organic carbon pools. Across watersheds the discharge to precipitation (D:P) ratio is the dominant determinant of how carbon yields respond to changes in precipitation, and watersheds with a high D:P ratio should demonstrate large changes in carbon yields with forecasted changes to precipitation.
Reconciling the electron counterstreaming and dropout occurrence rates with the heliospheric flux budget
Authors: Owens M. J. , Crooker N. U.
Published: June 2007

Counterstreaming electrons (CSEs) are treated as signatures of closed magnetic flux, i.e., loops connected to the Sun at both ends. However, CSEs at 1 AU likely fade as the apex of a closed loop passes beyond some distance R, owing to scattering of the sunward beam along its continually increasing path length. The remaining antisunward beam at 1 AU would then give a false signature of open flux. Subsequent opening of a loop at the Sun by interchange reconnection with an open field line would produce an electron dropout (ED) at 1 AU, as if two open field lines were reconnecting to completely disconnect from the Sun. Thus EDs can be signatures of interchange reconnection as well as the commonly attributed disconnection. We incorporate CSE fadeout into a model that matches time‐varying closed flux from interplanetary coronal mass ejections (ICMEs) to the solar cycle variation in heliospheric flux. Using the observed occurrence rate of CSEs at solar maximum, the model estimates R ∼ 8–10 AU. Hence we demonstrate that EDs should be much rarer than CSEs at 1 AU, as EDs can only be detected when the juncture points of reconnected field lines lie sunward of the detector, whereas CSEs continue to be detected in the legs of all loops that have expanded beyond the detector, out to R. We also demonstrate that if closed flux added to the heliosphere by ICMEs is instead balanced by disconnection elsewhere, then ED occurrence at 1 AU would still be rare, contrary to earlier expectations.
Anomalous resistivity by fluctuation in the lower‐hybrid frequency range
Authors: Yoon Peter H. , Lui Anthony T. Y.
Published: June 2007

The present paper discusses anomalous resistivity that arises from electrostatic fluctuation in the lower‐hybrid frequency range. The implicit physical situation is the vicinity of the reconnection onset region. By employing locally uniform approximation, the unmagnetized ion response and fully magnetized electron linear response are computed analytically. On the basis of the response functions, anomalous transport coefficients including the anomalous resistivity are constructed. An order‐of‐magnitude analysis reveals that the anomalous resistivity is much higher in magnitude than the classical resistivity. Dependence of the anomalous resistivity on plasma beta and the cross‐field drift speed is also discussed.
Present‐day climate forcing and response from black carbon in snow
Authors: Flanner Mark G. , Zender Charles S. , Randerson James T. , Rasch Philip J.
Published: June 2007

We apply our Snow, Ice, and Aerosol Radiative (SNICAR) model, coupled to a general circulation model with prognostic carbon aerosol transport, to improve understanding of climate forcing and response from black carbon (BC) in snow. Building on two previous studies, we account for interannually varying biomass burning BC emissions, snow aging, and aerosol scavenging by snow meltwater. We assess uncertainty in forcing estimates from these factors, as well as BC optical properties and snow cover fraction. BC emissions are the largest source of uncertainty, followed by snow aging. The rate of snow aging determines snowpack effective radius (re), which directly controls snow reflectance and the magnitude of albedo change caused by BC. For a reasonable re range, reflectance reduction from BC varies threefold. Inefficient meltwater scavenging keeps hydrophobic impurities near the surface during melt and enhances forcing. Applying biomass burning BC emission inventories for a strong (1998) and weak (2001) boreal fire year, we estimate global annual mean BC/snow surface radiative forcing from all sources (fossil fuel, biofuel, and biomass burning) of +0.054 (0.007–0.13) and +0.049 (0.007–0.12) W m−2, respectively. Snow forcing from only fossil fuel + biofuel sources is +0.043 W m−2 (forcing from only fossil fuels is +0.033 W m−2), suggesting that the anthropogenic contribution to total forcing is at least 80%. The 1998 global land and sea‐ice snowpack absorbed 0.60 and 0.23 W m−2, respectively, because of direct BC/snow forcing. The forcing is maximum coincidentally with snowmelt onset, triggering strong snow‐albedo feedback in local springtime. Consequently, the “efficacy” of BC/snow forcing is more than three times greater than forcing by CO2. The 1998 and 2001 land snowmelt rates north of 50°N are 28% and 19% greater in the month preceding maximum melt of control simulations without BC in snow. With climate feedbacks, global annual mean 2‐meter air temperature warms 0.15 and 0.10°C, when BC is included in snow, whereas annual arctic warming is 1.61 and 0.50°C. Stronger high‐latitude climate response in 1998 than 2001 is at least partially caused by boreal fires, which account for nearly all of the 35% biomass burning contribution to 1998 arctic forcing. Efficacy was anomalously large in this experiment, however, and more research is required to elucidate the role of boreal fires, which we suggest have maximum arctic BC/snow forcing potential during April–June. Model BC concentrations in snow agree reasonably well (r = 0.78) with a set of 23 observations from various locations, spanning nearly 4 orders of magnitude. We predict concentrations in excess of 1000 ng g−1 for snow in northeast China, enough to lower snow albedo by more than 0.13. The greatest instantaneous forcing is over the Tibetan Plateau, exceeding 20 W m−2 in some places during spring. These results indicate that snow darkening is an important component of carbon aerosol climate forcing.
Injection height of biomass burning aerosols as seen from a spaceborne lidar
Authors: Labonne Mathieu , Bréon François‐Marie , Chevallier Frédéric
Published: June 2007

This paper analyzes new lidar measurements from space over regions of biomass burning activity. The height of the aerosol layers deduced from the lidar observations is compared to the mixing layer top diagnosed from numerical weather forecasts, to identify whether or not the aerosols are directly injected in the free troposphere. During July and August 2006, the best cases (limited cloudiness, high density of fires) are found over South Africa and Northern Australia. Over these regions, the top of the aerosol layer is close to the mixing layer height, which is a strong indication that the aerosols are injected within the mixing layer. Other tropical areas with biomass burning activity are more difficult to interpret but the valid data support the same conclusion. For higher latitudes regions with biomass burning activity, although several aerosol plumes are identified above the mixing layer, most of the load is within the mixing layer. These observations made over a limited period and set of regions indicate that cases with pyro‐convection and/or direct injection to the free troposphere are not frequent.
Activation of the ERK signalling pathway contributes to the adaptive changes in rat hearts during naloxone‐induced morphine withdrawal
Authors: Almela P , Milanés M V , Laorden M L
Published: June 2007

Background and purpose:

We have previously demonstrated that morphine withdrawal induced hyperactivity of the heart by activation of noradrenergic pathways innervating the left and right ventricle, as evaluated by noradrenaline turnover and c‐Fos expression. The extracellular signal‐regulated kinase (ERK) has been implicated in drug addiction, but its role in activation of the heart during morphine dependence remains poorly understood. Here, we have looked for activation of ERK during morphine withdrawal and if this activation induced gene expression.

Experimental approach:

Dependence on morphine was induced by s.c. implantation of morphine pellets for 7 days. Morphine withdrawal was precipitated on day 8 by injection of naloxone (2 mg kg‐1, s.c.). ERK1/2, their phosphorylated forms and c‐Fos were measured by western blotting and immunohistochemistry of cardiac tissue.

Key results:

Naloxone‐induced morphine withdrawal activated ERK1/2 and increased c‐Fos expression in cardiac tissues. c‐Fos expression was blocked by SL327, a drug that prevents ERK activation.

Conclusions and implications:

These results indicate that signalling through the ERKs is necessary for morphine withdrawal‐induced hyperactivity of the heart and suggest that this pathway may also be involved in activation of immediate‐early genes in both cytosolic and nuclear effector mechanisms that have the potential to bring about long‐term changes in the heart.

British Journal of Pharmacology(2007)151, 787–797; doi:10.1038/sj.bjp.0707301
In silico pharmacology for drug discovery: methods for virtual ligand screening and profiling
Authors: Ekins S , Mestres J , Testa B
Published: June 2007

Pharmacology over the past 100 years has had a rich tradition of scientists with the ability to form qualitative or semi‐quantitative relations between molecular structure and activity in cerebro. To test these hypotheses they have consistently used traditional pharmacology tools such as in vivo and in vitro models. Increasingly over the last decade however we have seen that computational (in silico) methods have been developed and applied to pharmacology hypothesis development and testing. These in silico methods include databases, quantitative structure‐activity relationships, pharmacophores, homology models and other molecular modeling approaches, machine learning, data mining, network analysis tools and data analysis tools that use a computer. In silico methods are primarily used alongside the generation of in vitro data both to create the model and to test it. Such models have seen frequent use in the discovery and optimization of novel molecules with affinity to a target, the clarification of absorption, distribution, metabolism, excretion and toxicity properties as well as physicochemical characterization. The aim of this review is to illustrate some of the in silico methods for pharmacology that are used in drug discovery. Further applications of these methods to specific targets and their limitations will be discussed in the second accompanying part of this review.

British Journal of Pharmacology (2007) 152, 9–20; doi:10.1038/sj.bjp.0707305
Pharmacological enhancement of the endocannabinoid system in the nucleus accumbens shell stimulates food intake and increases c‐Fos expression in the hypothalamus
Authors: Soria‐Gómez E , Matias I , Rueda‐Orozco P E , Cisneros M , Petrosino S , Navarro L , Di Marzo V , Prospéro‐García O
Published: June 2007

Background and purpose:

Evidence indicates that the endocannabinoid, 2‐arachidonoylglycerol (2‐AG), increases food intake when injected into the nucleus accumbens shell (NAcS), thereby potentially activating hypothalamic nuclei involved in food intake regulation. We aimed to evaluate potential orexigenic effects of the endocannabinoid anandamide and of AA5HT, a fatty acid amide hydrolase (FAAH) inhibitor, and OMDM‐1, an inhibitor of anandamide uptake, injected in the NAcS, as well as the effect of these treatments on activation of hypothalamic nuclei.

Experimental approach:

Drugs were given into the NAcS of rats and food intake quantified during the next 4 h. In other groups, after the same treatments the brains were processed for c‐Fos immunohistochemistry with focus on hypothalamic nuclei. Additional groups were used to quantify endocannabinoid levels in the nucleus accumbens and the hypothalamus after AA5HT and OMDM‐1 intra‐NAcS injections.

Key results

Our results indicate that the above treatments stimulate food intake during 4 h post‐injection. They also increase c‐Fos immunoreactivity in hypothalamic nuclei. The CB1 antagonist, AM251, blocked these effects. Finally, we found elevated levels of 2‐AG, but not anandamide, after intra‐NAcS injections of AA5HT.

Conclusions and implications:

These data support the involvement of the endocannabinoid system in feeding behavior at the level of the NAcS and hypothalamus. In addition, this is the first experimental demonstration that the pharmacological inhibition of endocannabinoid inactivation in the NAcS stimulates food intake, suggesting that the endocannabinoid degrading proteins can be a target for treating eating disorders.

British Journal of Pharmacology (2007) 151, 1109–1116; doi:10.1038/sj.bjp.0707313
Estimates for the two-dimensional Navier–Stokes equations in terms of the Reynolds number
Authors: Gibbon J. D. , Pavliotis G. A.
Published: June 2007

The tradition in Navier–Stokes analysis of finding estimates in terms of the Grashof number Gr, whose character depends on the ratio of the forcing to the viscosity ν, means that it is difficult to make comparisons with other results expressed in terms of Reynolds number Re, whose character depends on the fluid response to the forcing. The first task of this paper is to apply the approach of Doering and Foias [C. R. Doering and C. Foias, J. Fluid Mech. 467, 289 (2002)] to the two-dimensional Navier–Stokes equations on a periodic domain [0,L]2 by estimating quantities of physical relevance, particularly long-time averages ⟨∙⟩, in terms of the Reynolds number Re=Uℓ∕ν, where U2=L−2⟨∥u∥22⟩ and ℓ is the forcing scale. In particular, the Constantin–Foias–Temam upper bound [P. Constantin, C. Foias, and R. Temam, Physica D 30, 284 (1988)] on the attractor dimension converts to aℓ2Re(1+lnRe)1∕3, while the estimate for the inverse Kraichnan length is (aℓ2Re)1∕2, where aℓ is the aspect ratio of the forcing. Other inverse length scales, based on time averages, and associated with higher derivatives, are estimated in a similar manner. The second task is to address the issue of intermittency: it is shown how the time axis is broken up into very short intervals on which various quantities have lower bounds, larger than long time averages, which are themselves interspersed by longer, more quiescent, intervals of time.
Electrical and optical simulation of organic light-emitting devices with fluorescent dopant in the emitting layer
Authors: Lee Chih-Chien , Chang Mei-Ying , Huang Ping-Tsung , Chen Yen Chun , Chang Yih , Liu Shun-Wei
Published: June 2007

A complete model for the quantitative simulation of electrical and optical characteristics for organic light-emitting devices with fluorescent dopant in the host is presented. This simulation model consists of three parts: charged carrier transport model, exciton model, and emission and optical model. In the first part, we include not only charge carrier trapping but also direct carrier recombination phenomena on the fluorescent dopant. In the second part, Förster [Discuss. Faraday Soc. 27, 7 (1959)] energy transfer from the host molecule to the dopant molecule is included in exciton model. In addition, the quenching phenomena related to dopant concentration and electrode are also considered in this study. In the optical model, the thin-film optics is applied to calculate the interference effect of the device. Results for several multilayer devices with different fluorescent dopant concentrations are presented. On the basis of the experimental data of a typical doped device, we have found good agreement between the simulation results and the experimental data.
Correlation between thermal diffusion and solvent self-diffusion in semidilute and concentrated polymer solutions
Authors: Rauch J. , Hartung M. , Privalov A. F. , Köhler W.
Published: June 2007

We have performed measurements of thermal diffusion coefficients DT and solvent self-diffusion coefficients Dss in semidilute to concentrated polymer solutions. Solutes of different glass transition temperatures and solvents of different solvent qualities have been used. The investigated systems are in detail: poly(dimethyl-siloxane) in toluene, tristyrene in toluene, polystyrene in toluene, polystyrene in tetrahydrofuran, polystyrene in benzene, and polystyrene in cyclohexane. The thermal diffusion data are compared to our data and literature data for solvent self-diffusion coefficients. In all systems the concentration dependence of DT closely parallels the one of Dss which may be viewed as a local probe for friction on a length scale of the size of one polymer segment. This identifies local friction as the dominating parameter determining the concentration dependence of DT. Solvent quality, in contrast, has no influence on DT.
Design and construction of uniform glow discharge plasma system operating under atmospheric condition
Authors: Koçum C. , Ayhan H.
Published: June 2007

The design of a uniform glow discharge plasma system operating without vacuum is presented. A full-bridge switching circuit was used to switch the transformers. The primary windings of transformers were connected in parallel, but in opposite phase to double the output voltage. Theoretically, 20000Vpp was obtained. Rectangle copper electrodes were used, and placed parallel to each other. To prevent the spark production that is, to obtain uniformity, two 2mm Teflon sheets were glued to the electrodes. However, it was observed that the operating frequency also affected the uniformity. For the system presented here, the frequency at which more uniformity was obtained was found to be 14kHz.
Light-emission properties of quantum dots embedded in a photonic double-heterostructure nanocavity
Authors: Stumpf Wolfgang C. , Fujita Masayuki , Yamaguchi Makoto , Asano Takashi , Noda Susumu
Published: June 2007

The authors report on the investigation of the light-emission properties of quantum dots in a photonic double-heterostructure nanocavity. The emission spectrum clearly allows the identification of the cavity and waveguide band edge modes. The frequency and polarization characteristics are in good agreement with three-dimensional finite-difference time-domain calculations. Resonant waveguide band edge mode excitation is demonstrated to reduce the background intensity that does not originate from the cavity and consequently cavity mode properties become evident. Finally, the Q value is estimated and discussed.
Space charge induced gating by a leaky gate
Authors: Spanheimer D. , Worschech L. , Müller C. R. , Forchel A.
Published: June 2007

The authors studied the role of gate leakage on the drain current in a monolithic, unipolar GaAs∕AlGaAs heterostructure based on three contacts leaky coupled to each other. Two in-plane barriers, each defined by a row of etched holes in a two-dimensional electron gas, separate the leaky gate from the central drain and the drain from the source. A pronounced decrease of the drain current sets in when the gate starts to leak associated with the space charge injected from the leaky gate.
Electron channeling contrast imaging of atomic steps and threading dislocations in 4H-SiC
Authors: Picard Y. N. , Twigg M. E. , Caldwell J. D. , Eddy C. R. , Neudeck P. G. , Trunek A. J. , Powell J. A.
Published: June 2007

Direct imaging of atomic step morphologies and individual threading dislocations in on-axis epitaxial 4H-SiC surfaces is presented. Topographically sensitive electron images of the crystalline surfaces were obtained through forescattered electron detection inside a conventional scanning electron microscope. This technique, termed electron channeling contrast imaging (ECCI), has been utilized to reveal the configuration of highly stepped, homoepitaxial 4H-SiC films grown on 4H-SiC mesa structures. Individual threading dislocations have been consistently imaged at the core of spiral atomic step morphologies located on the 4H-SiC surfaces. The ability of ECCI to image atomic steps was verified by atomic force microscopy.
Computer calculation of the Lorentz microscopy image and magnetic domain structure of weakly ordered FePt:C thin film
Authors: Kim M. C. , Oh S. J. , Park J. K. , Yang J. M.
Published: June 2007

A computer calculation technique of Lorentz microscopy image was developed and was applied to the analysis of the Lorentz microscopy image and magnetic domain structure of a weakly ordered FePt:C thin film for recording media. The magnetic domain structure was, at the as-deposited (random) state, a vortex network structure and evolved into the islandlike elongated reverse domain structure at the dc-demagnetization state, via a featherlike ripple structure at the remanent state. The magnetization reversal occurred not by the domain wall motion but by the local magnetization rotation to form a series of local vortices leading to the formation of reverse domains.
Microfiber knot dye laser based on the evanescent-wave-coupled gain
Authors: Jiang Xiaoshun , Song Qinghai , Xu Lei , Fu Jian , Tong Limin
Published: June 2007

The authors demonstrate a composite microring laser formed by immersing a silica microfiber knot in a rhodamine 6G dye solution. When the dye molecules are evanescently pumped by 532nm wavelength laser pulses guided along a 350μm diameter knot, lasing oscillation occurs inside the evanescently coupled closed-ring microcavity with a linewidth of about 0.06nm. Laser emission around 570 and 580nm wavelengths, which is evanescently coupled back into the microfiber, is observed with a threshold of about 9.2μJ∕pulse. The use of the microfiber knot cavity suggests a convenient and efficient approach to both pumping and collection of the evanescent-wave-coupled dye laser.
Scott Fraser: live action embryology
Authors: Williams Ruth
Published: June 2007

Using cutting-edge approaches to live imaging, Scott Fraser captures the dynamics of development.
Syndecan-2 induces filopodia and dendritic spine formation via the neurofibromin–PKA–Ena/VASP pathway
Authors: Lin Yi-Ling , Lei Ya-Ting , Hong Chen-Jei , Hsueh Yi-Ping
Published: June 2007

Syndecan-2 induced filopodia before spinogenesis; therefore, filopodia formation was used here as a model to study the early downstream signaling of syndecan-2 that leads to spinogenesis. Screening using kinase inhibitors indicated that protein kinase A (PKA) is required for syndecan-2–induced filopodia formation in both human embryonic kidney cells and hippocampal neurons. Because neurofibromin, a syndecan-2–binding partner, activates the cyclic adenosine monophosphate pathway, the role of neurofibromin in syndecan-2–induced filopodia formation was investigated by deletion mutant analysis, RNA interference, and dominant-negative mutant. The results showed that neurofibromin mediates the syndecan-2 signal to PKA. Among actin-associated proteins, Enabled (Ena)/vasodilator-stimulated phosphoprotein (VASP) were predicted as PKA effectors downstream of syndecan-2, as Ena/VASP, which is activated by PKA, induces actin polymerization. Indeed, when the activities of Ena/VASP were blocked, syndecan-2 no longer induced filopodia formation. Finally, in addition to filopodia formation, neurofibromin and Ena/VASP contributed to spinogenesis. This study reveals a novel signaling pathway in which syndecan-2 activates PKA via neurofibromin and PKA consequently phosphorylates Ena/VASP, promoting filopodia and spine formation.
A novel cell response triggered by interphase centromere structural instability
Authors: Morency Eric , Sabra Mirna , Catez Frédéric , Texier Pascale , Lomonte Patrick
Published: June 2007

Interphase centromeres are crucial domains for the proper assembly of kinetochores at the onset of mitosis. However, it is not known whether the centromere structure is under tight control during interphase. This study uses the peculiar property of the infected cell protein 0 of herpes simplex virus type 1 to induce centromeric structural damage, revealing a novel cell response triggered by centromere destabilization. It involves centromeric accumulation of the Cajal body–associated coilin and fibrillarin as well as the survival motor neuron proteins. The response, which we have termed interphase centromere damage response (iCDR), was observed in all tested human and mouse cells, indicative of a conserved mechanism. Knockdown cells for several constitutive centromere proteins have shown that the loss of centromeric protein B provokes the centromeric accumulation of coilin. We propose that the iCDR is part of a novel safeguard mechanism that is dedicated to maintaining interphase centromeres compatible with the correct assembly of kinetochores, microtubule binding, and completion of mitosis.
Two compound heterozygous mutations (c.215delA/c.2422T→C and c.387delC/c.1159G→A) in the thyroid peroxidase gene responsible for congenital goitre and iodide organification defect
Authors: Rivolta Carina M. , Louis‐Tisserand Mariana , Varela Viviana , Gruñeiro‐Papendieck Laura , Chiesa Ana , González‐Sarmiento Rogelio , Targovnik Héctor M.
Published: June 2007

Background  Iodide organification defects are frequently but not always associated with mutations in the thyroid peroxidase (TPO) gene and characterized by a positive perchlorate discharge test. These mutations phenotypically produce a congenital goitrous hypothyroidism, with an autosomal recessive mode of inheritance.

Objectives  In the present study we extended our initial molecular studies in six unrelated patients heterozygous for the TPO mutations, in order to identify the second mutation in this autosomal recessive disease.

Methods  The promoter and the complete coding regions of the human TPO and DUOXA2 genes, along with the flanking regions of each intron were analysed by direct DNA sequencing.

Results  Four different inactivating TPO mutations were identified in two patients: two novel mutations (c.215delA [p.Q72fsX86] and c.1159G→A [p.G387R]) and two previously reported (c.387delC [p.N129fsX208] and c.2422T→C [p.C808R]), confirming the inheritance of two different compound heterozygous mutations, c.215delA/c.2422T→C and c.387delC/c.1159G→A. The remaining four patients did not show additional inactivating mutations in the TPO gene and all had only the wild type sequencing in the DUOXA2 gene.

Conclusions  We have reported two patients with iodide organification defect caused by two compound heterozygous mutations, c.215delA/c.2422T→C [p.Q72fsX86/p.C808R] and c.387delC/c.1159G→A [p.N129fsX208/p.G387R], in the TPO gene and four patients with monoallelic TPO defect. Identification of the molecular basis of this disorder might be helpful for understanding the pathophysiology of congenital hypothyroidism.
Impact of the high‐molecular‐weight form of adiponectin on endothelial function in healthy young men
Authors: Torigoe Masayuki , Matsui Hideo , Ogawa Yasuhiro , Murakami Hisashi , Murakami Ryuichiro , Cheng Xian Wu , Numaguchi Yasushi , Murohara Toyoaki , Okumura Kenji
Published: June 2007

Objective  Adiponectin is an adipocyte‐derived, antiatherogenic protein that is present in plasma as a large multimeric structure of high molecular weight (HMW) and in a trimer or hexamer form (non‐HMW). The biological activities of these isoforms have not yet been elucidated. We therefore examined the effect of these isoforms on endothelial function in healthy young men.

Design  One hundred apparently healthy young men without overt cardiovascular disease (mean age 30 years) were recruited in this cross‐sectional study based on voluntary enrolment.

Measurements  We evaluated endothelial function estimated by flow‐mediated dilatation (FMD) of the brachial artery during reactive hyperaemia, and measured total and HMW adiponectin levels.

Results  Both HMW and non‐HMW adiponectin levels showed a significant, inverse correlation with body mass index (BMI). FMD was significantly correlated with fasting insulin, homeostasis model assessment of insulin resistance (HOMA‐IR), malondialdehyde‐modified low density lipoprotein (MDA‐LDL), LDL particle size, and HMW adiponectin (r = 0·320, P = 0·001), but not non‐HMW adiponectin (r = 0·125, P = 0·22). In multivariate analysis, HMW adiponectin and MDA‐LDL were selected as independent factors capable of influencing FMD. No variables determined nitroglycerin‐induced dilatation.

Conclusions  These results suggest that even in young men, plasma adiponectin levels can predict endothelial dysfunction before any overt vascular disease has occurred. HMW adiponectin may be more useful as a marker of endothelial dysfunction than total adiponectin.
Corticosteroid‐binding globulin gene polymorphisms: clinical implications and links to idiopathic chronic fatigue disorders
Authors: Torpy D. J. , Ho J. T.
Published: June 2007

Corticosteroid‐binding globulin (CBG) binds cortisol with high affinity, facilitating transport of cortisol in blood, although tissue‐specific CBG–cortisol interactions have long been postulated. There are three heritable, human CBG gene mutations that can reduce CBG–cortisol binding affinity and/or reduce circulating CBG levels. In some families, fatigue and low blood pressure have been associated with affinity altering or CBG level reducing mutations. The limited numbers of reports raise the possibility of ascertainment bias as many cases presented with features suggesting cortisol deficiency. The recent description of a genetically CBG‐deficient mouse listed fatigue, manifest as reduced activity levels, as part of the phenotype, which also included immune aberrations. Severe CBG mutations may produce fatigue, but one study suggests that these are a rare cause of idiopathic fatigue. A mechanism for the effect of CBG mutations on fatigue is not readily apparent because free cortisol levels are normal, although we speculate that CBG may have an effect on cortisol–brain transport.
The membrane protein universe: what's out there and why bother?
Authors: Von Heijne G.
Published: June 2007

Chances are that you have come across membrane proteins many times in your professional life: ion channels, aquaporins, G‐protein‐coupled receptors, drug resistance proteins. But it is also quite likely that you have never bothered to think about what the implications are of being a membrane protein, as opposed to a soluble protein. What is special about membrane proteins in terms of structure and function, how many membrane proteins are out there, how are they made in the cell? Welcome to the membrane protein universe!