bluuebunny/crossref_metadata_2025 huggingface dataset:
Association of intronic polymorphism rs3773364 A>G in synapsin‐2 gene with idiopathic epilepsy
Authors: Lakhan Ram , Kalita J. , Misra U.K. , Kumari Ritu , Mittal Balraj
Published: December 2009

In epilepsy, there is a tendency towards recurrent unprovoked seizures. Seizures result due to the excessive electrical misfiring in the brain between neurons and disturbance in neurotransmitter release. Several gene products affect the behavior of these neurons by regulating neurotransmission via several mechanisms. One such gene, Synapsin‐2 (SYN2), involved in synaptogenesis is also reported to regulate the neurotransmitter release. We hypothesized that SYN2 gene and its polymorphisms could affect the process of epileptogenesis and therapeutic response in humans. In this hospital‐based study, we enrolled 372 patients with epilepsy and 199 control subjects. We selected rs3773364 A>G polymorphism in SYN2 gene and analyzed its distribution in north Indian patients with epilepsy and control subjects. Genotyping was carried out by polymerase chain reaction‐restriction fragment length polymorphism (PCR‐RFLP) method. According to the results obtained, SYN2 “AG” genotype frequency was significantly higher in patients with epilepsy versus control subjects in north Indian population (P = 0.02, OR = 1.55, 95% CI = 1.06–2.26). After subclassification, we observed higher frequency of AG genotype in idiopathic patients as compared to control subjects (P = 0.01, OR = 1.67, 95% CI = 1.08–2.56). There were no significant differences in genotypic (AG: OR = 0.80, P = 0.377; GG: P = 0.628, OR = 1.17) or allelic (P = 0.86, OR = 1.03) frequency distributions in patients with multiple drug resistance versus patients with drug‐responsive epilepsy. Results from our study indicate the involvement of SYN2 gene polymorphism in conferring risk to epilepsy; however, the genetic variant does not seem to modulate drug‐response in epilepsy pharmacotherapy. Synapse 64:403–408, 2010. © 2009 Wiley‐Liss, Inc.
Cesarean section scar defects: agreement between transvaginal sonographic findings with and without saline contrast enhancement
Authors: Vikhareva Osser O. , Jokubkiene L. , Valentin L.
Published: December 2009

Objectives

To determine the agreement between transvaginal ultrasound examinations performed before and at saline contrast sonohysterography (SCSH) with regard to number, size and shape of Cesarean section (CS) scar defects.

Methods

In all, 108 women underwent transvaginal ultrasound examination with SCSH at least 6 months after CS: 68 had undergone one CS, 32 two CSs and eight women had undergone at least three CSs. The ultrasound examiner was blinded to the number of CSs and to the obstetric history. The number and shape of CS scar defects were determined subjectively, and any scar defect was estimated subjectively to be large or not large. Measurements of the scar defects were also taken. Results obtained before and at SCSH were compared.

Results

Most scar defects were triangular in shape. The shape did not change at SCSH, but the ultrasound examiner found it easier to delineate the borders of the scar defects at SCSH than at unenhanced ultrasound examination. More scar defects were seen and more scar defects were classified as large at SCSH than before: among the 100 women who had undergone one or two CSs, 16 additional women had large defects at SCSH, whereas no woman with a large defect before SCSH had no defect or only a small defect at SCSH. The length and height of the defects were larger at SCSH than before: mean difference 2 mm and 1 mm in women who had undergone one CS, and mean difference 4 mm and 2 mm in the lowest‐positioned scar in women who had undergone two CSs.

Conclusions

In non‐pregnant women CS scars were better evaluated at SCSH than at unenhanced ultrasound examination, because the demarcations of scar defects were more clearly delineated at SCSH than before. More defects were detected and more defects were classified as large at SCSH. Copyright © 2009 ISUOG. Published by John Wiley & Sons, Ltd.
Prevalence and perinatal outcome of dichorionic and monochorionic twins with nuchal translucency above the 99th percentile and normal karyotype
Authors: Goncé A. , Borrell A. , Meler E. , Arigita M. , Martínez J. M. , Botet F. , Sánchez A. , Gratacós E.
Published: December 2009

Objective

To evaluate the prevalence of and perinatal outcome associated with increased nuchal translucency thickness (NT) > 99th percentile in dichorionic and monochorionic twins with normal karyotype.

Methods

Two hundred and six consecutive twin pregnancies (166 dichorionic and 40 monochorionic) underwent an NT scan during a 4‐year period. In those with NT > 99th percentile and normal karyotype, we performed first‐ and second‐trimester anomaly scans, fetal echocardiography at 14–16 and 20–22 weeks, maternal serology and, in monochorionic pregnancies, serial ultrasound examinations every other week. Perinatal outcome was recorded.

Results

There were 10 (4.95%) pregnancies in which one of the fetuses had NT > 99th percentile and normal karyotype, including five fetuses (1.5%) in dichorionic and five (6.25%) in monochorionic pregnancies. During the same period the prevalence of NT > 99th percentile and normal karyotype in singleton pregnancies studied in our center was 2.6%. Among the 10 twins affected, six (60%) were diagnosed with structural abnormalities (three dichorionic and three monochorionic), and two intrauterine fetal demises occurred (one dichorionic and one monochorionic). Thus, the perinatal outcome was normal in only two of the pregnancies, one dichorionic and one monochorionic.

Conclusions

The prevalence of NT > 99th percentile in dichorionic twins with a normal karyotype is similar to that in singletons. In monochorionic twins we confirmed previous studies reporting an increased prevalence compared with singletons. NT > 99th percentile with a normal karyotype in twins was associated with a high rate of fetal abnormalities and/or fetal demise (overall 80%) irrespective of chorionicity. Copyright © 2009 ISUOG. Published by John Wiley & Sons, Ltd.
Episodic memory versus episodic foresight: Similarities and differences
Authors: Suddendorf Thomas
Published: December 2009

There are logical and empirical grounds that link episodic memory and the ability to imagine future events. In some sense, both episodic memory and episodic foresight may be regarded as two sides of the same capacity to travel mentally in time. After reviewing some of the recent evidence for commonalities, I discuss limits of these parallels. There are fundamental differences between thinking about past and future events that need to be kept in clear view if we are to make progress in understanding the nature of mental time travel. The reviewed evidence suggests that mental time travel is based on a complex system selected not for accuracy about past and future per se, but for fitness benefits. Functional analyses promise to lead to fruitful avenues for future research. Copyright © 2009 John Wiley & Sons, Ltd.

This article is categorized under:

Psychology > Memory

Neuroscience > Cognition
Positive selection on apoptosis related genes
Authors: da Fonseca Rute R. , Kosiol Carolin , Vinař Tomáš , Siepel Adam , Nielsen Rasmus
Published: December 2009

Apoptosis is a form of programmed cell death crucial for development, homeostasis, immunity, spermatogenesis, and prevention of cancer. Positive selection acting on mammalian apoptosis related genes targets protein interfaces that interact with pathogens and also elements of signaling complexes. Selection appears primarily to be driven by the immune/defense related function of these genes. Moreover, competitive interactions could be driving positive selection among sperm cells, as well as the need for protection against female anti‐sperm immune responses. Trade‐offs in fitness are expected out of these selective pressures, which could explain the involvement of these genes in various diseases, including cancer.
The yeast aquaglyceroporin Fps1p is a bidirectional arsenite channel
Authors: Maciaszczyk-Dziubinska Ewa , Migdal Iwona , Migocka Magdalena , Bocer Tomasz , Wysocki Robert
Published: December 2009

The stress‐activated kinase Hog1p mediates arsenic tolerance by decreasing arsenite influx through the aquaglyceroporin Fps1p in Saccharomyces cerevisiae. Unexpectedly, we found that overexpression of FPS1 increased arsenite tolerance suggesting a physiological role of Fps1p in arsenic detoxification. Consistently, during arsenite treatment transcription of FPS1 gene was strongly upregulated, while Fps1p was not degraded and remained localized to the plasma membrane. Moreover, deletion of FPS1 gene resulted in arsenate sensitivity. Finally, transport experiments revealed that Fps1p in concert with the arsenite transporter Acr3p mediates arsenite efflux.
Mechanical stimulation suppresses phosphorylation of eIF2α and PERK‐mediated responses to stress to the endoplasmic reticulum
Authors: Hirasawa Hideyuki , Jiang Chang , Zhang Ping , Yang Feng-Chun , Yokota Hiroki
Published: December 2009

Cellular perturbations such as stress to the endoplasmic reticulum induce an integrated stress response, which activates phosphorylation of eIF2α and leads to alleviation of cellular injury or apoptosis. This study investigated the role of mechanical stimulation in the regulation of eIF2α and cell death. Mechanical stimulation was applied to mouse ulnae, MC3T3 cells, and mesenchymal stem cells. The results demonstrate that mechanical stimulation reduces phosphorylation of eIF2α through inactivation of Perk. Furthermore, flow pre‐treatment reduces thapsigargin‐induced cell mortality through suppression of phosphorylation of Perk. However, H2O2‐driven cell mortality, which is not mediated by Perk, is not suppressed by mechanical stimulation. Taken together, our observations suggest a pro‐survival role of mechanical stimulation in Perk‐mediated stress responses.
Panky, a novel photoreceptor‐specific ankyrin repeat protein, is a transcriptional cofactor that suppresses CRX‐regulated photoreceptor genes
Authors: Sanuki Rikako , Omori Yoshihiro , Koike Chieko , Sato Shigeru , Furukawa Takahisa
Published: December 2009

Neuronal gene transcription is regulated by both transcriptional activators and repressors. While the roles of transactivators in retinal photoreceptor development have been well characterized, the roles of repressors have been poorly understood. We isolated Panky/Ankrd33, a gene encoding an ankyrin repeat‐containing protein. Panky‐A was specifically expressed in retinal photoreceptors and the pineal gland, and its expression was directly up‐regulated by the CRX transcription factor. Subcellular localization of PANKY‐A was observed in the nucleus and cytoplasm. Additionally, transactivation analysis suggested that PANKY‐A is a transcriptional cofactor that suppresses CRX‐activated photoreceptor genes. Furthermore, we found by an electrophoretic mobility shift assay that PANKY inhibited the DNA‐binding activity of CRX.
Democratization, media and elections: Electoral reform in Mexico
Authors: Arechavaleta Carlos Manuel Rodríguez
Published: December 2009

The two last elections in Mexico – one for president, the other legislative – have taken place in an atmosphere of growing competitiveness and high political uncertainty, which has strained relations among the players involved. The electoral governance of increasingly inclusive regulations which facilitated the development of a moderate multiparty democracy seems not to guarantee the legitimacy and quality of the electoral process. The article analyzes the electoral reforms of 2008 with an emphasis on the media and the effect of reforms on the behavior of the different players involved: the parties, the dual structure of the media, the arbiter, and the audiences–voters.
The Acquisition of Aspect and Modality
Authors: Aksu-Koç Ayhan
Published: December 2009

Ayhan Aksu-Koç's empirical research on Turkish children's acquisition of the past tense forms the basis for this original and important contribution to the current debate among psycholinguistics on the interrelationship between language and cognitive development. Turkish, in its grammar, makes a clear distinction between direct and indirect experiencing, separating personal observation of processes from both inference and narrative. This distinction thus provides an ideal means by which linguistic and nonlinguistic conceptual development can be observed. Dr Aksu-Koç has exploited this to full advantage in her broadly based longitudinal and cross-sectional study, conducted across a wide age range. The data are meticulously analyzed, and the theoretical implications for a neo-Piagetian paradigm are carefully considered.
The Abandoned Narcotic
Authors: Brunton Ron
Published: December 2009

Ron Brunton revives a problem posed by the great anthropologist W. H. R. Rivers in History of Melanesian Society (1914): how to explain the strange geographical distribution of kava, a narcotic drink once widely consumed by south-west Pacific islanders. Rivers believed that it was abandoned by many people even before European contact in favour of another drug, betel, drawing his speculations from the ideas of the diffusionist school of anthropology. However, Dr Brunton disagrees. Taking the varying fortunes of kava on the island of Tanna, Vanauta, as his starting point, he suggests that kava's abandonment can best be explained in terms of its association with unstable religious cults, and not because of the adoption of betel. The problem of kava is therefore part of a broader problem of why many traditional Melanesian societies were characteristically highly unstable, and Dr Brunton sees this instability as both an outcome and a cause of weak institutions of authority and social coordination.
Wages and Unemployment
Authors: Picard Pierre
Published: December 2009

This book is concerned with the problem of wage rigidities in macroeconomic theory, and their implications for public policy. It offers an analysis of the microeconomic foundations of rigid wages, considering their implications for normative economics, and their role in explaining involuntary unemployment. The initial chapters examine short-run macroeconomic equilibrium with nominal rigidities within the framework of fixed-price temporary equilibria. This is followed by an overview and assessment of the main microeconomic mechanisms likely to account for real wage rigidity. In this context new findings concerning microeconomic mechanisms likely to account for real wage rigidity, including implicit contract theory, union behaviour and efficiency wage models are reported. The effect of efficiency wages on macroeconomic fluctuations is also considered. Finally an analysis of the important public policy issues raised in the book is provided.
Abortion in Judaism
Authors: Schiff Daniel
Published: December 2009

Abortion in Judaism presents a complete Jewish legal history of abortion from the earliest relevant biblical references through the end of the twentieth century. For the first time, almost every Jewish text relevant to the abortion issue is explored in detail. These texts are investigated in historical sequence, thereby elucidating the development inherent within the Jewish approach to abortion. Following the examination of the foundational sources, a range of contemporary responses from across the Jewish spectrum is also introduced in order to probe their place in this history, as well as to discern the directions in which they would have the law proceed. The impact of Jewish abortion law upon Israeli legislative enactments is evaluated, along with the social outcomes of such legislation. Finally, the work considers the insights that this thematic history provides into Jewish ethical principles, as well as into the role of halakhah within Judaism.
Trends in food and nutritional intakes of French adults from 1999 to 2007: results from the INCA surveys
Authors: Dubuisson Carine , Lioret Sandrine , Touvier Mathilde , Dufour Ariane , Calamassi-Tran Gloria , Volatier Jean-Luc , Lafay Lionel
Published: December 2009

Two independent cross-sectional dietary surveys (the Individual and National Food Consumption Surveys, INCA), performed in 1998–99 (INCA1) and in 2006–07 (INCA2) on nationally representative samples of French people, were used to analyse trends in the dietary habits and nutritional intake of French adults. Food consumption was recorded through 7-d dietary records, and nutritional intakes were assessed using the French food composition database. After exclusion of under-reporters, analyses were performed on 3267 adults, aged 18–79 years: 1345 from INCA1 and 1922 from INCA2. The trends highlighted over the 8-year period showed a decrease in consumption of dairy products, meat, bread, potatoes, pastries/croissant-like pastries/cakes/biscuits and sugar/confectionery. In contrast, the consumption of fruits and vegetables, rice, ice cream and chocolate increased. Other food groups, like fish and snacking foods, remained stable. Food choices were mostly age specific. These age differences remained consistent over the years and underlined two opposite dietary trends: a ‘traditional’ one mainly followed by the elderly, and a ‘snacking and convenience’ one mainly adopted by young adults. The overall trends in food consumption did not influence the mean energy intake, but did slightly modify the contribution of each macronutrient to energy intake. These repeated surveys highlighted the fact that trends in French food habits have moved towards an average European diet at the crossroads between Mediterranean and Northern diets, and that food consumption changes impacted, to a lesser extent, nutritional intake.
Native and microwaved bean and pea starch preparations: physiological effects on the intestinal ecosystem, caecal tissue and serum lipids in rats
Authors: Krupa-Kozak Urszula , Juśkiewicz Jerzy , Wronkowska Małgorzata , Soral-Śmietana Maria , Zduńczyk Zenon
Published: December 2009

Dietary beans and peas provide fibre, resistant starch and other nutrients that are often lacking in the human diet. The influence of native starches of beans and peas (and microwaved preparations) on N utilisation, biochemical indices in blood serum and caecal ecosystem state (SCFA, bacterial enzymes, micro-organisms) was studiedin vivo. The native pea starch contained more resistant starch compared with its bean counterpart (31v.17 %); however, processing decreased these amounts to 25v.10 %. N digestibility was found to decrease considerably in all experimental groups. A considerable reduction was observed in glucose and total cholesterol concentration in rat blood serum as a result of feeding both dietary legume starch preparations under microwave treatment. This indicates that starch of bean origin activated glycolytic bacterial enzymes; however, all the analysed starches were found to reduce the activity of β-glucuronidase. In addition, both dietary bean starches significantly induced the formation of SCFA in the caecal digesta. As compared with the control group, a significant decrease in the pH of caecal and colonic digesta was demonstrated for both bean starch preparations. In comparison with the diet with native pea starch, its microwaved preparation reduced the concentrations of acetic, butyric and propionic acids among caecal SCFA and increased the pH of caecal and colonic digesta. The atherogenic index was significantly lower in rats fed microwaved pea starch. All investigated starch preparations increased the population ofBifidobacteriumspp. in caecal digesta, but were also good substrates for opportunisticEnterococcusorEscherichia coli.
Mechanisms of non-modal energy amplification in channel flow between compliant walls
Authors: HŒPFFNER JÉRÔME , BOTTARO ALESSANDRO , FAVIER JULIEN
Published: December 2009

The mechanisms leading to large transient growth of disturbances for the flow in a channel with compliant walls are investigated. The walls are modelled as thin spring-backed plates, and the flow dynamics is modelled using the Navier–Stokes equations linearized round the Poiseuille profile. Analysis for streamwise invariant perturbations show that this fluid-structure system can sustain oscillatory energy evolution of large amplitude, in the form of spanwise standing waves. Such waves are related to the travelling waves which a free wall can support, modified to account for an ‘added mass’ effect. Simple scaling arguments are found to provide results in excellent agreement with computations of optimal disturbances, for low-to-moderate values of the stiffness parameter characterizing the compliant surface.
Solving the nonlinear shallow-water equations in physical space
Authors: ANTUONO M. , BROCCHINI M.
Published: December 2009

The boundary value problem for the nonlinear shallow-water equations with a beach source term is solved by direct use of physical variables, so that solutions are more easily inspected than those obtained by means of hodograph transformations. Beyond an overall description of the near-shoreline flows in terms of the nonlinear shallow-water equations, significant results are provided by means of a perturbation approach which enables much of the information on the flow to be retained. For sample waves of interest (periodic and solitary), first-order solutions of the shoreline motion and of the near-shoreline flows are computed, illustrated and successfully compared with the equivalent ones obtained through a hodograph transformation method previously developed by the authors. Wave–wave interaction, both at the seaward boundary and within the domain, is also accurately described. Analytical conditions for wave breaking within the domain are provided. These, compared with the authors' hodograph model, show that the first-order condition of the present model is comparable to the second-order condition of that model.
Algebraically decaying modes and wave packet pseudo-modes in swept Hiemenz flow
Authors: OBRIST DOMINIK , SCHMID PETER J.
Published: December 2009

The modal structure of the swept Hiemenz flow, a model for the flow near the attachment line of a swept wing, consists of eigenfunctions which exhibit (super-)exponential or algebraic decay as the wall-normal coordinate tends to infinity. The subset of algebraically decaying modes corresponds to parts of the spectrum which are characterized by a significant sensitivity to numerical discretization. Numerical evidence further suggests that a continuous spectrum covering a two-dimensional range of the complex plane exists. We investigate the family of uniform swept Hiemenz modes using eigenvalue computations, numerical simulations and the concept of wave packet pseudo-modes. Three distinct branches of the family of algebraically decaying eigenmodes are identified. They can be superimposed to produce wavefronts propagating towards or away from the boundary layer and standing or travelling wave packets in the free stream. Their role in the exchange of information between the free stream and the attachment-line boundary layer for the swept Hiemenz flow is discussed. The concept of wave packet pseudo-modes has been critical in the analysis of this problem and is expected to lead to further insights into other shear flows in semi- or bi-infinite domains.
Acetate and succinate production in amoebae, helminths, diplomonads, trichomonads and trypanosomatids: common and diverse metabolic strategies used by parasitic lower eukaryotes
Authors: BRINGAUD F. , EBIKEME C. , BOSHART M.
Published: December 2009

Parasites that often grow anaerobically in their hosts have adopted a fermentative strategy relying on the production of partially oxidized end products, including lactate, glycerol, ethanol, succinate and acetate. This review focuses on recent progress in understanding acetate production in protist parasites, such as amoebae, diplomonads, trichomonads, trypanosomatids and in the metazoan parasites helminths, as well as the succinate production pathway(s) present in some of them. We also describe the unconventional organisation of the tricarboxylic acid cycle associated with the fermentative strategy adopted by the procyclic trypanosomes, which may resemble the probable structure of the primordial TCA cycle in prokaryotes.
Collective stopping power in laser driven fusion plasmas for block ignition
Authors: Malekynia B. , Hora H. , Azizi N. , Kouhi M. , Ghoranneviss M. , Miley G.H. , He X.T.
Published: December 2009

In contrast to the usual laser fusion scheme with spherical irradiation and very high compression and ignition of fuel, the alternative scheme with side-on ignition of uncompressed solid density of fuel (Chu) may lead to a solution by using the now available picosecond laser pulses with higher than petawatt power. A necessary condition is to use clean laser pulses with better than 108contrast ratio for suppression of relativistic self-focusing. When updating the analysis of Chu for fusion of deuterium-tritium and proton-11B, one problem is that the correct use of the stopping power of the alpha particles had to be solved. Discrepancies are evaluated in view of the stopping power at the low temperature range of the plasmas where the change of the emitted bremsstrahlung is involved.
Propagation of laser generated plasmas through inert gases
Authors: Neri F. , Ossi P.M. , Trusso S.
Published: December 2009

A fast photo imaging technique has been used to characterize the expansion dynamics of a laser generated silver plasma propagating through background inert gases (He and Ar) at different pressures. The time evolution of the expanding plasma was investigated in the framework of currently available phenomenological models. Mixed-propagation model gives an accurate description of the initial and late plasma expansion stages in Ar when proper input parameters are taken into account. In He, only the initial quasi-linear expansion and shock wave formation were observed along the space available to plasma motion.
Practical tools and methods for health technology assessment in Europe: Structures, methodologies, and tools developed by the European network for Health Technology Assessment, EUnetHTA
Authors: Kristensen Finn Børlum , Lampe Kristian , Chase Deborah L. , Lee-Robin Sun Hae , Wild Claudia , Moharra Montse , Garrido Marcial Velasco , Nielsen Camilla Palmhøj , Røttingen John-Arne , Neikter Susanna Allgurin , Bistrup Marie Louise
Published: December 2009

Objectives: This article presents an overview of the practical methods and tools to support transnational Health Technology Assessment (HTA) that were developed and pilot tested by the European network for HTA (EUnetHTA), which involved a total of sixty-four Partner organizations.

Methods: The methods differ according to scope and purpose of each of the tools developed. They included, for example, literature reviews, surveys, Delphi and consensus methods, workshops, pilot tests, and internal/public consultation.

Results: Practical results include an HTA Core Model and a Handbook on the use of the model, two pilot examples of HTA core information, an HTA Adaptation Toolkit for taking existing reports into new settings, a book about HTA and health policy making in Europe, a newsletter providing structured information about emerging/new technologies, an interactive Web-based tool to share information about monitoring activities for emerging/new technologies, and a Handbook on HTA capacity building for Member States with limited institutionalization of HTA.

Conclusions: The tools provide high-quality information and methodological frameworks for HTA that facilitate preparation of HTA documentation, and sharing of information in and across national or regional systems. The tools will be used and further tested by partners in the EUnetHTA Collaboration aiming to (i) help reduce unnecessary duplication of HTA activities, (ii) develop and promote good practice in HTA methods and processes, (iii) share what can be shared, (iv) facilitate local adaptation of HTA information, (v) improve the links between health policy and HTA.
The HTA Core Model: A novel method for producing and reporting health technology assessments
Authors: Lampe Kristian , Mäkelä Marjukka , Garrido Marcial Velasco , Anttila Heidi , Autti-Rämö Ilona , Hicks Nicholas J. , Hofmann Björn , Koivisto Juha , Kunz Regina , Kärki Pia , Malmivaara Antti , Meiesaar Kersti , Reiman-Möttönen Päivi , Norderhaug Inger , Pasternack Iris , Ruano-Ravina Alberto , Räsänen Pirjo , Saalasti-Koskinen Ulla , Saarni Samuli I. , Walin Laura , Kristensen Finn Børlum
Published: December 2009

Objectives:The aim of this study was to develop and test a generic framework to enable international collaboration for producing and sharing results of health technology assessments (HTAs).

Methods:Ten international teams constructed theHTA Core Model, dividing information contained in a comprehensive HTA into standardized pieces, theassessment elements. Each element contains a generic issue that is translated into practical research questions while performing an assessment. Elements were described in detail inelement cards. Two pilot assessments, designated asCore HTAswere also produced. The Model and Core HTAs were both validated. Guidance on the use of the HTA Core Model was compiled into aHandbook.

Results: The HTA Core Model considers health technologies through nine domains. Two applications of the Model were developed, one for medical and surgical interventions and another for diagnostic technologies. Two Core HTAs were produced in parallel with developing the model, providing the first real-life testing of the Model and input for further development. The results of formal validation and public feedback were primarily positive. Development needs were also identified and considered. An online Handbook is available.

Conclusions:The HTA Core Model is a novel approach to HTA. It enables effective international production and sharing of HTA results in a structured format. The face validity of the Model was confirmed during the project, but further testing and refining are needed to ensure optimal usefulness and user-friendliness. Core HTAs are intended to serve as a basis for local HTA reports. Core HTAs do not contain recommendations on technology use.
The Cultural Heritage Law Committee of the International Law Association: Special Session, June 8, 2009, Geneva, Switzerland
Authors: Paterson Robert K. , Nafziger James A. R.
Published: December 2009

In August 2008 the Seventy-third Conference of the International Law Association (ILA) in Rio de Janeiro adopted the Cultural Heritage Law Committee's “Guidelines for the Establishment and Conduct of Safe Havens for Cultural Material,” the text of which appears in this issue. The Committee, after discussing its on-going project concerning the relationship between international trade law and the protection of cultural heritage, decided to focus on national export controls.
Salzburg Global Seminar: Achieving the Freer Circulation of Cultural Artifacts (Session 453, May 9–14, 2008)
Authors: Seidl-Fox Susanna
Published: December 2009

From May 9–14, 2008, the Salzburg Global Seminar convened its 453rd session—and its annual arts and culture session—on “Achieving the Freer Circulation of Cultural Artifacts” at Schloss Leopoldskron in Salzburg. Sixty two participants from twenty-nine countries gathered for the five-day session, aimed at building consensus among cultural authorities and museum representatives from around the world on ways to overcome legal, political, and practical obstacles to the circulation of cultural objects. Participants worked together to identify and assess new and better ways to promote the sharing of art and artifacts—from virtual access to practical strategies for significantly expanding loan programs worldwide. Whereas there are many museum conferences worldwide, few strive to bring together a multi-disciplinary and truly global group of participants for an open, informal exchange of thoughts and ideas in a neutral setting. The gathering in Salzburg, generously supported by The Edward T. Cone Foundation, succeeded in providing an evaluative international forum of this type, which brought diverse experts from a range of national and professional contexts into dialogue and gave them the opportunity to reflect deeply and openly on ways to increase the international exchange of cultural artifacts.
A mathematical model of the indirect effects of rotavirus vaccination
Authors: VAN EFFELTERRE T. , SORIANO-GABARRÓ M. , DEBRUS S. , CLAIRE NEWBERN E. , GRAY J.
Published: December 2009

Rotavirus (RV) infections progressively confer natural immunity against subsequent infection. Similarly to natural infection, vaccination with a live attenuated vaccine potentially reduces RV transmission and induces herd protection. A mathematical transmission model was developed to project the impact of a vaccination programme on the incidence of RV infection and disease for five countries in the European Union. With vaccination coverage rates of 70%, 90% and 95% the model predicted that, in addition to the direct effect of vaccination, herd protection induced a reduction in RV-related gastroenteritis (GE) incidence of 25%, 22% and 20%, respectively, for RV-GE of any severity, and of 19%, 15%, and 13%, respectively, for moderate-to-severe RV-GE, 5 years after implementation of a vaccination programme.
Health Equity and Development: the Commission on Social Determinants of Health
Authors: Marmot Michael , Bell Ruth
Published: December 2009

From the start, the WHO Commission on Social Determinants of Health built its case for taking action on the social determinants of health, unashamedly, on principles of social justice. Quite simply, the Commission stated that health inequities in the sense of avoidable and preventable differences in health between countries, and between groups within countries according to income, occupation, education, ethnicity or between men and women, are unjust. Taking this position has brought praise and blame: praise for the Commission’s boldness in putting fairness on the global health agenda1 in the face of the dominant global model of economic growth as an end in itself, and blame for the Commission’s unworldliness in apparently not recognising that economic arguments push the political agenda.
How does Alcohol Kill Cells?
Authors: Criddle David N.
Published: December 2009

Excessive alcohol consumption is linked to a variety of major health problems, including the severe inflammation of the pancreas, which may lead to premature death of the individual.1Hospital admissions in the United Kingdom due to acute pancreatitis were recently shown to have doubled over a 30 year period,2in parallel with an estimated doubling of alcohol consumption in this country, and the incidence of the disease is dramatically increasing. Within the European Union, acute pancreatitis may attain an incidence of up to 1 per 1000 individuals per year. In accord with trends in drinking lifestyle in the UK, admissions of younger people and women have correspondingly escalated over the last few decades, and alcohol-related problems have placed a heavy financial burden on the healthcare system. So-called ‘binge drinking’, a prevalent feature of the current ‘drinking culture’, is commonly linked to patients presenting at clinic with episodes of acute pancreatitis, often manifested initially as excruciating abdominal pain and vomiting. Of these individuals, approximately 20% will develop a more extensive form of the disease with significant pancreatic necrosis triggering a systemic inflammatory response syndrome (SIRS) that may cause multiple organ failure; up to a third of these patients will die. The extent of necrotic cell death in these patients is a major determinant of the severity of acute pancreatitis and disease outcome.3However, the precise way in which alcohol triggers the cellular damage that forms the basis of this severe and debilitating disease has remained elusive.
Norway’s European ‘Gag Rules’
Authors: Fossum John Erik
Published: December 2009

As part of their conflict handling repertoire, political systems possess a range of mechanisms to suppress or avoid conflicts. A closer look across Europe would yield a broad tapestry of mechanisms for handling the thorny issue of European integration, with most governments and political systems relying on some version of conflict avoidance. In this picture, one should expect that a country such as Norway, which has rejected EU membership twice, has an active and vocal anti-membership organization, and where polls consistently show a ‘no’ majority, would stand out as the exception, in the sense that there would be no need for the Norwegian political system to take any measures to suppress the issue. But reality is more complex. Since the early 1990s, when Norway entered into the EEA agreement with the EU, Norway’s relationship to the EU has changed dramatically. Norway’s current arrangement with the EU is perhaps best labelled as ‘tight incorporation without formal membership’. This situation is managed through arrangements not to raise the EU membership issue. In this article, I rely on Stephen Holmes’s notion of ‘gag rules’, as a particular means of issue avoidance. This mechanism speaks of how actors seek to remove debate on a controversial issue that does not go away: it is a matter of stymieing debate on the issue but not stopping to deal with it. If anything, the lid on debate on EU membership helps the political system to keep alive an active process of Norwegian adaptation to the EU, with serious implications for Norwegian democracy.
Assessing contributions to panevaporation trends in Haihe River Basin, China
Authors: Zheng Hongxing , Liu Xiaomang , Liu Changming , Dai Xiangqian , Zhu Ruirui
Published: December 2009

In many places around the world, panevaporation has been detected to decrease with the increase in temperature, which is known as the “panevaporation paradox.” An example of the paradox was found in the Haihe River Basin from 1957 to 2001. To explain the mechanism of the paradox, an approach to quantify the contributions of climate factors to the panevaporation trend has been proposed, in which the individual contribution was defined as the product of the partial derivative and slope of the trend for the concerned variables. Four variables, including temperature, wind speed, solar radiation, and vapor pressure, were selected based on the Penman‐Monteith method to assess their individual contribution to the panevaporation trend. The results showed that an increase in temperature resulted in the increase of panevaporation, but this effect had been offset by an increase in vapor pressure and decrease in wind speed and solar radiation. Wind speed was the dominant factor contributing to panevaporation decreases in the Haihe River Basin.
Discovery of functional motifs in h-regions of trypanosome signal sequences
Authors: Duffy Josh , Patham Bhargavi , Mensa-Wilmot Kojo
Published: December 2009

N-terminal signal peptides direct secretory proteins into the ER (endoplasmic reticulum) of eukaryotes or the periplasmic space of prokaryotes. A hydrophobic core (h-region) is important for signal sequence function; however, the mechanism of h-region action is not resolved. To gain new insight into signal sequences, bioinformatic analysis of h-regions from humans, Saccharomyces cerevisiae, Trypanosoma brucei and Escherichia coli was performed. Each species contains a unique set of peptide motifs (h-motifs) characterized by identity components (i.e. sequence of conserved amino acids) joined by spacers. Human h-motifs have four identity components, whereas those from the other species utilize three identity components. Example of h-motifs are human Hs3 {L-x(2)-[AGILPV]-L-x(0,2)-L}, S. cerevisiae Sc1 [L-x(0,2)-S-x(0,3)-A], T. brucei Tb2 {L-x(1,2)-L-[AILV]} and E. coli Ec1 [A-x(0,2)-L-x(0,3)-A]. The physiological relevance of h-motifs was tested with a T. brucei microsomal system for translocation of a VSG (variant surface glycoprotein)-117 signal peptide. Disruption of h-motifs by scrambling of sequences in h-regions produced defective signal peptides, although the hydrophobicity of the peptide was not altered. We conclude that: (i) h-regions harbour h-motifs, and are not random hydrophobic amino acids; (ii) h-regions from different species contain unique sets of h-motifs; and (iii) h-motifs contribute to the biological activity of ER signal peptides. h-Regions are ‘scaffolds’ in which functional h-motifs are embedded. A hypothetical model for h-motif interactions with a Sec61p protein translocon is presented.
Molecular mechanism of elongation factor 1A inhibition by a Legionella pneumophila glycosyltransferase
Authors: Hurtado-Guerrero Ramon , Zusman Tal , Pathak Shalini , Ibrahim Adel F. M. , Shepherd Sharon , Prescott Alan , Segal Gil , van Aalten Daan M. F.
Published: December 2009

Legionnaires' disease is caused by a lethal colonization of alveolar macrophages with the Gram-negative bacterium Legionella pneumophila. LpGT (L. pneumophila glucosyltransferase; also known as Lgt1) has recently been identified as a virulence factor, shutting down protein synthesis in the human cell by specific glucosylation of EF1A (elongation factor 1A), using an unknown mode of substrate recognition and a retaining mechanism for glycosyl transfer. We have determined the crystal structure of LpGT in complex with substrates, revealing a GT-A fold with two unusual protruding domains. Through structure-guided mutagenesis of LpGT, several residues essential for binding of the UDP-glucose-donor and EF1A-acceptor substrates were identified, which also affected L. pneumophila virulence as demonstrated by microinjection studies. Together, these results suggested that a positively charged EF1A loop binds to a negatively charged conserved groove on the LpGT structure, and that two asparagine residues are essential for catalysis. Furthermore, we showed that two further L. pneumophila glycosyltransferases possessed the conserved UDP-glucose-binding sites and EF1A-binding grooves, and are, like LpGT, translocated into the macrophage through the Icm/Dot (intracellular multiplication/defect in organelle trafficking) system.
N-terminal chimaeras with signal sequences enhance the functional expression and alter the subcellular localization of heterologous membrane-bound inorganic pyrophosphatases in yeast
Authors: Drake Rocío , Serrano Aurelio , Pérez-Castiñeira José R.
Published: December 2009

Expression of heterologous multispanning membrane proteins in Saccharomyces cerevisiae is a difficult task. Quite often, the use of multicopy plasmids where the foreign gene is under the control of a strong promoter does not guarantee efficient production of the corresponding protein. In the present study, we show that the expression level and/or subcellular localization in S. cerevisiae of a heterologous type of multispanning membrane protein, the proton-translocating inorganic pyrophosphatase (H+-PPase), can be changed by fusing it with various suitable N-terminal signal sequences. Chimaeric proteins were constructed by adding the putative N-terminal extra domain of Trypanosoma cruzi H+-PPase or the bona fide signal sequence of S. cerevisiae invertase Suc2p to H+-PPase polypeptides of different organisms (from bacteria to plants) and expressed in a yeast conditional mutant deficient in its cytosolic PPi hydrolysis activity when grown on glucose. Chimaeric constructs not only substantially enhanced H+-PPase expression levels in transformed mutant cells, but also allowed functional complementation in those cases in which native H+-PPase failed to accomplish it. Activity assays and Western blot analyses demonstrated further the occurrence of most H+-PPase in internal membrane fractions of these cells. The addition of N-terminal signal sequences to the vacuolar H+-PPase AVP1 from the plant Arabidopsis thaliana, a protein efficiently expressed in yeast in its natural form, alters the subcellular distribution of the chimaeras, suggesting further progression along the secretory sorting pathways, as shown by density gradient ultracentrifugation and in vivo fluorescence microscopy of the corresponding GFP (green fluorescent protein)–H+-PPase fusion proteins.
Selective inhibition of β-F1-ATPase mRNA translation in human tumours
Authors: Willers Imke M. , Isidoro Antonio , Ortega Álvaro D. , Fernández Pedro L. , Cuezva José M.
Published: December 2009

Down-regulation of β-F1-ATPase (the catalytic subunit of the mitochondrial H+-ATP synthase) is a hallmark of many human tumours. The expression level of β-F1-ATPase provides a marker of the prognosis of cancer patients, as well as of the tumour response to chemotherapy. However, the mechanisms that participate in down-regulating its expression in human tumours remain unknown. In the present study, we have investigated the expression of β-F1-ATPase mRNA (termed β-mRNA) in breast, colon and lung adenocarcinomas and squamous carcinomas of the lung. Despite the down-regulation of the protein, tumour β-mRNA levels remained either unchanged (breast and lung adenocarcinomas) or significantly increased (colon and squamous lung carcinomas) when compared with paired normal tissues, suggesting a specific translation-masking event for β-mRNA in human cancer. Consistently, we show using cell-free translation assays that a large fraction (~70%) of protein extracts derived from breast and lung adenocarcinomas specifically repress the translation of β-mRNA. We show that the 3′UTR (3′ untranslated region) of human β-mRNA is a relevant cis-acting element required for efficient translation of the transcript. However, an RNA chimaera bearing the 3′UTR of human β-mRNA does not recapitulate the inhibitory effect of tumour extracts on β-mRNA translation. Overall, the findings of the present study support the hypothesis that down-regulation of the bioenergetic activity of mitochondria in human tumours is exerted by translation silencing of β-mRNA.
Bivariate Genetic Analyses of Stuttering and Nonfluency in a Large Sample of 5-Year-Old Twins
Authors: van Beijsterveldt Catharina Eugenie Maria , Felsenfeld Susan , Boomsma Dorret Irene
Published: December 2009

Purpose

Behavioral genetic studies of speech fluency have focused on participants who present with clinical stuttering. Knowledge about genetic influences on the development and regulation of normal speech fluency is limited. The primary aims of this study were to identify the heritability of stuttering and high nonfluency and to assess the relative contribution of genetic and environmental factors to the correlation between these 2 fluency phenotypes.

Method

Information on 6 specific speech fluency behaviors was obtained by maternal report for over 10,500 5-year-old Dutch twin pairs.

Results

Genetic analyses revealed that both fluency phenotypes were moderately heritable, with heritability estimates of 42% and 45% for probable stuttering and high nonfluency, respectively. Shared environmental factors were also significant, explaining 44% of the individual differences in probable stuttering and 32% in nonfluency. For both phenotypes, the magnitude of the genetic and environmental influences did not differ between boys and girls. The overlap between the 2 traits was substantial (tetrachoric correlation was .72). A bivariate genetic analysis showed that this overlap was due to both overlapping genetic and environmental influences.

Conclusions

These findings provide a foundation to justify further studies in normal fluency control, a scientific area that has received little cross-disciplinary attention.
Lineshape theory of photoluminescence from semiconductor alloys
Authors: Grundmann Marius , Dietrich Christof P.
Published: December 2009

The photoluminescence from semiconductor alloys is inhomogeneously broadened due to alloy disorder. We present a model to explain the so-called “S-shape” temperature dependence of peak position, taking into account recombination of free excitons and excitons bound to impurities. We find the following effects to contribute with increasing temperature: exciton localization on impurities at low temperatures, exciton transfer between impurities, exciton ionization from impurities, transfer of excitons between potential minima in the disorder potential, and shrinkage of band gap. We extend the common theory of ionization of excitons from impurities to take into account impurity ionization. We find this effect essential for our lineshape theory. The lineshape theory describes quantitatively the temperature dependent peak position in MgxZn1−xO alloys.