bluuebunny/crossref_metadata_2025 huggingface dataset:
State-dependent constitutive model and numerical solution of self-weight consolidation
Authors: Hawlader B. C. , Muhunthan B. , Imai G.
Published: June 2008

A new constitutive model is developed for the compressibility behaviour of soft clay sediments at low effective stress level. Central to this model is the realisation that at low effective stress levels the void ratio–effective stress paths of soil elements are non-unique, and dependent very much on their state. Beyond a threshold stress level, these relationships become unique. These observations have been used to develop a state-dependent constitutive model for the compressibility behaviour of soft sediments. Methods to obtain the input parameters of the model are discussed. The proposed model is used to solve finite-strain one-dimensional consolidation with pertinent initial and boundary conditions. The analyses performed using a finite difference computer code predict better the observed phenomena associated with self-weight consolidation, especially during its early stages. The comparison of the predictions shows that the present model can capture the decrease in void ratio patterns, as observed in experiments at low effective stresses, and which cannot be modelled using existing constitutive relationships.
Mechanics of tunnelling machine screw conveyors: a theoretical model
Authors: Merritt A. S. , Mair R. J.
Published: June 2008

A new theoretical model describing the total pressure gradient and torque in a tunnelling machine screw conveyor is proposed. The theory develops new equations relating the pressure gradient and torque to the screw geometry, the shear stresses acting in the screw conveyor, and the material flow. The equations are expressed in dimensionless form, allowing application to screw conveyors of different scales. The theory is validated against measurements from laboratory model screw conveyor tests with clay soils with varying properties and operating conditions. The theory successfully describes key features of the observed mechanics of the model conveyor operation, and accurately predicts the test measurements. The proposed theory provides insight into the fundamental mechanics of screw conveyor operations, and can be used in the design of tunnelling machine screw conveyors. The theory can also be applied to other forms of screw conveyors and extruders operating with plastic materials.
Insight into seismic earth and water pressures against caisson quay walls
Authors: Dakoulas P. , Gazetas G.
Published: June 2008

Motivated by the need to explain the large displacement and rotation that numerous caisson-type quay walls suffered in the port of Kobe during the devastating 1995 earthquake, a detailed numerical analysis is presented for the response of such a wall from Rokko Island. Utilising the Pastor–Zienkiewicz elastoplastic constitutive model, an effective stress dynamic analysis is performed using as input the accelerogram recorded 32 m below the ground surface in the nearby Port Island. The evolution during shaking of lateral displacements, plastic strains and pore water pressures sheds some light on the complex interplay of several simultaneously occurring phenomena: the development of oscillatory inertia forces on the wall, in phase or out of phase with the backfill soil and water pressures; the simple-shear seismic deformation of the soil and the ensuing initial development of positive excess pore water pressures in the backfill and the foundation soil; the extensional deformation developing in the ‘active wedge’ behind the wall, with the ensuing generation of negative excess pore water pressures; and the continuous dissipation and redistribution of water pressures. The conventional generalised Mononobe–Okabe theory is also reviewed, and extensive comparisons are made with the numerically computed effective and water pressures against the wall. Finally, a surprising role of the relative density of rubble behind the wall is highlighted.
Immunomodulation by Mesenchymal Stem Cells
Authors: Abdi Reza , Fiorina Paolo , Adra Chaker N. , Atkinson Mark , Sayegh Mohamed H.
Published: June 2008

Mesenchymal stem cells (MSCs) are pluripotent stromal cells that have the potential to give rise to cells of diverse lineages. Interestingly, MSCs can be found in virtually all postnatal tissues. The main criteria currently used to characterize and identify these cells are the capacity for self-renewal and differentiation into tissues of mesodermal origin, combined with a lack in expression of certain hematopoietic molecules. Because of their developmental plasticity, the notion of MSC-based therapeutic intervention has become an emerging strategy for the replacement of injured tissues. MSCs have also been noted to possess the ability to impart profound immunomodulatory effects in vivo. Indeed, some of the initial observations regarding MSC protection from tissue injury once thought mediated by tissue regeneration may, in reality, result from immunomodulation. Whereas the exact mechanisms underlying the immunomodulatory functions of MSC remain largely unknown, these cells have been exploited in a variety of clinical trials aimed at reducing the burden of immune-mediated disease. This article focuses on recent advances that have broadened our understanding of the immunomodulatory properties of MSC and provides insight as to their potential for clinical use as a cell-based therapy for immune-mediated disorders and, in particular, type 1 diabetes.
Review: Angiotensin-converting enzyme in skeletal muscle: sentinel of blood pressure control and glucose homeostasis
Authors: Dietze Guenther J , Henriksen Erik J
Published: June 2008

Recent evidence suggests a coordinated regulation by the local renin-angiotensin system (RAS) and tissue kallikrein-kinin system (TKKS) of blood flow and substrate supply in oxidative red myofibres of skeletal muscle tissue during endurance exercise.The performance of these myofibres is dependent on the increased oxidation of substrates facilitated by augmenting nutritive blood flow and glucose uptake. Humoral factors released by the contracting fibres, such as adenosine and kinins, are suggested to be responsible for this metabolic adjustment.The considerable drain of blood volume and the enormous consumption of glucose during endurance exercise require a control mechanism for the maintenance of blood pressure (BP) and glucose homeostasis. This is achieved by the sympathetic nervous system and its subordinate RAS, which is located in the nutritive vessels and parenchyma of the red myofibres. The angiotensin-converting enzyme (ACE) is the primary enzyme responsible for kinin degradation during exercise, underscoring the important interrelationship between the RAS and the TKKS in the critical role of kinins in the multifactorial regulation of muscle bioenergetics and glucose and BP homeostasis. Importantly, overactivity of the ACE, as occurs inindividuals displaying risk factors such as overweight, causes exaggerated BP response and reduced glucose disposal. If they persist over years, compensatory responses to this ACE overactivity, such as hypersecretion of insulin and compliance of the vessel walls, will inevitably be exhausted, leading ultimately to the manifestation of type 2 diabetes and hypertension. This concept also provides a unifying explanation for the beneficial effects of ACE-inhibitors and Angiotensin II receptor antagonists in the treatment of hypertension and insulin resistance.
Intracellular and extracellular renin have opposite effects on the regulation of heart cell volume. Implications for myocardial ischaemia
Authors: De Mello Walmor C
Published: June 2008

The influence of intracellular renin plus angiotensinogen (Ao) as well as angiotensin (Ang) II on cell volume was investigated in myocytes isolated from the heart of four-month-old cardiomyopathic hamsters (TO-2) and normal hamsters (F1B). Measurements of cell width and cell length were performed on quiescent cells using a Px-it imaging and computer system.The cell volume was calculated assuming the cells as elliptical cylinders and taking the cell depth equal to one third of cell width. For measurements of sodium pump current, the cells were voltage clamped (holding potential -40 mV) using the whole cell configuration. Cells were exposed to K-free solution to inhibit the pump and then to normal Krebs solution to reactivate the pump. In other experiments the cells were voltage clamped (holding potential -40 mV)and changes in the background current elicited by renin plus Ao or by Ang II were monitored. The results indicated that: a) intracellular dialysis of renin (128 pmol Ang I/ml) plus Ao (110 pmol Ang I generated by renin by exhaustion) decreased the cell volume concurrently with the activation of the sodium pump; b) intracellular losartan (10-8 M) or extracellular ouabain (10-8 M) abolished the effect of renin plus Ao on cell volume; c) intracellular Ang II (10-8 M), by itself, reduced cell volume and increased the pump current density; d) extracellular administration of renin plus Ao, at the same concentration used intracellularly, increased cell volume and inhibited the sodium pump. This increase of cell volume elicited by extracellular renin plus Ao was related to the activation of the Na-K-2Cl cotransporter; e) intracellular Ang II (10-8 M) reversed cell swelling induced by hypotonic solutions. Conclusions. Intracellular and extracellular renin plus Ao have opposite effects on sodium pump and cell volume regulation in the failing heart. Both effects of renin plus Ao are dependent upon the formation of Ang II. Since intracellular Ang II counteracted the cell swelling induced by hypotonic solution, it is reasonable to think that the activation of the intracrine renin-angiotensin system might play a protective role during myocardial ischaemia by reducing cell volume.
Review: Cardioprotective effects of telmisartan in uncomplicated and complicated hypertension
Authors: Grassi Guido , Quarti-Trevano Fosca , Mancia Giuseppe
Published: June 2008

The development of angiotensin II receptor blockers (ARB) as a new class of drugs for the management of hypertension has elicited the attention of many clinicians worldwide with the aim of improving blood pressure (BP) control as well as cardiovascular protection.AmongARB telmisartan has been shown to be characterised by an antihypertensive efficacy fully covering the 24-hour period, thereby allowing to antagonise the adverse effects of early morning BP rise on cardiovascular risk. Other specific effects of the drug are represented by its favourable metabolic profile (particularly on insulin sensitivity) and neutral effects on sympathetic cardiovascular function.These properties are coupled with cardioprotective effects, documented by the evidence that the drug: 1) is effective in favouring the regression of cardiac and vascular organ damage, 2) reduces arterial stiffness and improves vascular distensibility and 3) reverses the endothelial dysfunction typical of the hypertensive state particularly when complicated by renal failure, diabetes, obesity or metabolic syndrome. Several of these properties can account for the results of the ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial (ONTARGET), documenting the beneficial effects on the drug on cardiovascular morbidity and mortality.
Effect of Temperature, Wettability and Relative Permeability on Oil Recovery from Oil-wet Chalk
Authors: Hamouda Aly A. , Karoussi Omid
Published: June 2008

It is customary, for convenience, to use relative permeability data produced at room temperature. This paper shows that this practice underestimates oil recovery rates and ultimate recovery from chalk rocks for high temperature reservoirs. Above a certain temperature (80°C in this work) a reduction of oil recovery was observed. The reduction in oil recovery is reflected by the shift of relative permeability data towards more oil-wet at high temperature (tested here 130°C). However, both IFT and contact angle measurements indicate an increase in water wetness as temperature increases, which contradict the results obtained by relative permeability experiments. This phenomenon may be explained based on the total interaction potential, which basically consists of van der Waals attractive and short-range Born repulsive and double layer electrostatic forces. The fluid/rock interactions is shown to be dominated by the repulsive forces above 80°C, hence increase fine detachment enhancing oil trapping. In other words the indicated oil wetness by relative permeability is misleading.
Energies and Policies
Authors: Kessler Edwin
Published: June 2008

The International Energy Agency, headquartered in Paris, was founded in the early 1970s and is an energy policy advisor to 27 countries.[...]
Betulinic Acid for Cancer Treatment and Prevention
Authors: Fulda Simone
Published: June 2008

Betulinic acid is a natural product with a range of biological effects, for example potent antitumor activity. This anticancer property is linked to its ability to induce apoptotic cell death in cancer cells by triggering the mitochondrial pathway of apoptosis. In contrast to the cytotoxicity of betulinic acid against a variety of cancer types, normal cells and tissue are relatively resistant to betulinic acid, pointing to a therapeutic window. Compounds that exert a direct action on mitochondria present promising experimental cancer therapeutics, since they may trigger cell death under circumstances in which standard chemotherapeutics fail. Thus, mitochondrion-targeted agents such as betulinic acid hold great promise as a novel therapeutic strategy in the treatment of human cancers.
Modeling and Forecasting the Volatility of Long-stay Tourist Arrivals
Authors: Lorde Troy , Moore Winston
Published: June 2008

Volatility is an important characteristic of most tourist economies. Fluctuations in tourist arrivals can occur due to unanticipated events, such as natural disasters, crime, the threat of terrorism, and business cycles in key source markets. This study exploits recent time series modeling techniques to model and forecast the volatility in monthly international tourist arrivals to Barbados. The results show models that allow mean volatility to change over time tend to have the best forecasting performance. However, relatively simple models, such as the RiskMetrics approach, can also produce predictions that are statistically at least as good as more complex models.
The Life Cycle of a Terrorism Crisis: Impact on Tourist Travel
Authors: Moss Steven E. , Ryan Chuck , Moss Janet
Published: June 2008

The impact of terrorist events on various business sectors has been widely publicized, and the tourism travel industry has been one of the most impacted industries. Prior work has shown that air travel is affected by a terrorist incident within the region in which it occurred. This
research is the first to model the magnitude of the episode, the duration of the effect, and the shape of life the cycle. Two terrorism events that affected tourist air travel are analyzed: 9/11 and the Madrid train bombings. Our findings suggest that the impact on tourist air travel from
these catastrophes follow scalable and fad life cycles, respectively. These results have significant implications for the tourism travel industry, which are identified and discussed.
The Influence of Nationality on the Generation of Tourist Satisfaction with a Destination
Authors: Campo Sara , Garau Joan B.
Published: June 2008

Academic literature and empirical studies have demonstrated that consumer satisfaction is a good indicator of the financial results of businesses and tourist destinations. An analysis of tourist satisfaction and how to improve satisfaction levels is therefore crucial, not just for business
profits but also for a destination's economic development, especially in the case of resorts that have reached a mature stage of development where visitors must be conserved in order to remain competitive. The aims of this article are to analyze and measure tourist satisfaction with one of
the most popular, mature resorts in the Mediterranean, the Balearic Islands, and, from these results, to detect differences in tourist satisfaction depending on their nationality. The results show that by measuring satisfaction as a multidimensional construct, it is possible to identify the
key variables in generating overall satisfaction. At the same time, the results also help decision makers at destinations to improve satisfaction levels by prioritizing how they invest, concentrating on aspects that play a key role in generating satisfaction. The results also reveal differences
in the generation of satisfaction depending on the tourists' nationalities. This finding is crucial in understand tourists' buying behavior and it may become a basic tool in helping destinations to adapt and improve their commercial facilities and infrastructure to meet the specific expectations
of each nationality.
Tourism Satellite Accounts and Impact Assessments: Some Considerations
Authors: Jones Calvin , Munday Max
Published: June 2008

The agreement between international agencies that Tourism Satellite Accounts (TSA) are the most appropriate way to measure the economic contribution of tourism has led to an explosion in the number of countries (and regions) developing such accounts. In reliably reconciling visitor
supply and demand, TSAs offer improved information for tourism policy development and economic impact assessments, both of which are important in guiding resources and support for new tourism infrastructure and individual events. There are, however, a number of conceptual and structural issues
that limit the usefulness of the TSA for economic modeling purposes. This article suggests that while the collection and manipulation of information that supports the TSA will aid impact and policy assessment, a further reengineering of the TSA framework is necessary to lever the full benefits
for such studies. The TSA is found to be ideally used as a basis for complementary modeling techniques, including that of Computable General Equilibrium and Social Accounting Matrices.
Symptoms of Complexity in a Tourism System
Authors: Baggio Rodolfo
Published: June 2008

Tourism destinations behave as dynamic evolving complex systems, encompassing numerous factors and activities that are interdependent and whose relationships might be highly nonlinear. Traditional research in this field has looked after alinearapproach: variables and relationships are monitored in order to forecast future outcomes with simplified models and to derive implications for management organizations. The limitations of this approach have become apparent in many cases, and several authors claim for a new and different attitude. While complex systems ideas are among the most promising interdisciplinary research themes emerged in the last few decades, very little has been done so far in the field of tourism. This article presents a brief overview of the complexity framework as a means to understand structures, characteristics, and relationships, and explores the implications and contributions of the complexity literature on tourism systems. The objective is to allow the reader to gain a deeper appreciation of this point of view.
Computer-based System of Tourism and Recreational Systems Study and Optimization
Authors: Shcherbina Oleg , Shembeleva Elena
Published: June 2008

This article discusses a methodology for development and validation of a comprehensive computer-based system of tourism and recreational systems study and optimization (CBSTRS) that is based on mathematical modeling of the recreational system and its processes, to assist planners in
evaluating alternative scenarios and planning options. This allows empowering the organizational front-line by giving people systems with which they can solve their own problems, as distinct from the traditional approach of having specialists solve problems and then deliver solutions to the
problem owners. The CBSTRS is a model-based decision support system (DSS) designed to work with data describing tourism and recreational systems, or, in other words, the CBSTRS is a database system with data describing recreational systems as well as a set of operations and mathematical models
for working with the data. Proposed technology integrates common database operations such as query and statistical analysis with the unique possibility for mathematical modeling and analysis benefits offered by the system. These abilities distinguish the CBSTRS from usual information systems
and make it valuable to a wide range of public and private enterprises for modeling and analyzing planning strategies for recreational systems.
Japanese Backpacking: The Emergence of a New Market Sector—A Queensland Case Study
Authors: Prideaux Bruce , Shiga Hideki
Published: June 2008

This article reports on a study of Japanese backpackers conducted in Queensland, arguing that this backpacker sector has a range of characteristics that differ from Western backpackers who, to date, have constituted the main representatives of this segment visiting Australia. The research
identified a number of areas where the characteristics of Japanese backpackers varied from those of the overall backpacker population in Australia. One major point of difference was the emphasis placed by this market segment on learning English and a preference for activities that focused
on the environment rather than other activities such as soft adventure.
The Dialectics of Japanese Overseas Tourists: Transformation in Holiday Making
Authors: Takai-Tokunaga Noriko
Published: June 2008

This research examines transformational process of tourist experience in the context of fast changing Japanese outbound tourism. The Western perspective of this market is predominantly that of organized mass tourists. However, as the market matures, a diverse style of overseas holiday
making among the Japanese becomes increasingly evident: more independent and versatile tourists have recently emerged. A qualitative approach based on the constructivist perspective was chosen because a standardized survey research was recognized as being neither able to reveal the complex
and interwoven processes and mechanisms of such transformation nor an evolutionary scenario of the Japanese outbound market. Semistructured interviews were conducted with 17 Japanese citizens who had holidayed to Britain. Thematic coding and narrative analysis were applied to the interview
data to identify essential thematic domains for understanding critical factors that have affected their transformation of holiday making. It was recognized that the Japanese tourist lives through a dialectical-optimizing transformational process of holiday making in order to seek an optimal
holiday experience. Collective changes and recent trends in Japanese outbound tourism may reflect an aggregation of such an individual's transformational process.
Japanese Inns (Ryokan) in Atami (Japan) and the Shaping of Coming "Traditions"
Authors: Guichard-Anguis Sylvie
Published: June 2008

This article stems from the assumption that researching Japanese inns (ryokan) located in Atami (45,000 inhabitants, Shizuoka Prefecture) would allow the reader to understand what happens elsewhere among other ryokan in Japanese spas (onsen). After briefly introducing
the history of spas in Japan, three different approaches constitute an attempt to explore the development of ryokan in Atami. From its historical origin to its most prosperous economic period between the mid-1960s and the mid-1970s, Atami has taken advantage of its location close to
the capital to develop mainly as a recreational place, based on the spas' (onsen) function. Historically, lodging associated with this function came to take the form of Japanese inns (ryokan), characterized today by a great variety of scales and shapes. The several international
hotels that have also been developed still represent a minority, as is the case in most of the recreational cities of Japan. The main historical periods of development are emphasized in order to understand the different layers of history to which the present inns belong. From the approximately
68 ryokan still in business compared to the 361 in 1972, three case studies are introduced to describe their diversity. The economic difficulties encountered nowadays by this kind of lodging in Atami and the different solutions sought show a tendency to create new patterns of lodging.
In the new economic environment, they may offer opportunities to keep a balance between preserving some historical aspects of ryokan and creating new models for the future.
Preparation and catalysis of chloromethylated polystyrene‐supported macrocyclic Schiff base metal complexes for the oxidation of cumene
Authors: Chang Yue , Shi Xiulong , Zhu Dongmei , Liu Yan
Published: June 2008

Chloromethylated polystyrene‐supported macrocyclic Schiff base metal complexes (PS‐L‐M, M = Cu2+, Co2+, Ni2+, and Mn2+) were synthesized and characterized by the methods of IR, ICP, and small area X‐ray photoelectron spectroscopy (XPS). The oxidation of cumene by molecular oxygen in the absence of solvent with the synthesized complexes employed as catalyst was carried out. In comparison with their catalytic activities, PS‐L‐Cu is a more effective catalyst for the oxidation of cumene. The main products are 2‐phenyl‐2‐propanol (PP) and cumene hydroperoxide, which were measured by GC/MS. The influences of reaction temperature, the amount of catalyst, as well as the reaction time on the oxidation of cumene were investigated. Copyright © 2008 John Wiley & Sons, Ltd.
Evaluation of a Peer‐Led Mutual Support Group for Chinese Families of People with Schizophrenia
Authors: Chien Wai-Tong , Thompson David R. , Norman Ian
Published: June 2008

Family interventions in schizophrenia have shown positive effects on patients but little attention has been paid to their effects on family members, particularly those in non‐Western countries. This randomized controlled trial evaluated the effectiveness of a bi‐weekly, 12‐session, family‐led mutual support group for Chinese caregivers of schizophrenia sufferers over 6 months compared with standard psychiatric care. It was conducted with 76 families of outpatients with schizophrenia in Hong Kong of whom 38 were assigned randomly to either a mutual support group or standard care. Families' psychosocial health status and patients' symptom severity and length of re‐hospitalizations at recruitment, one‐week and 12‐month post‐intervention were compared between groups. Results of repeated‐measures mixed model indicated that the mutual support group experienced significantly greater improvements in families' burden, functioning and number of support persons and length of patients' re‐hospitalizations at two post‐tests. The findings provide evidence that mutual support groups can be an effective family‐initiated, community‐based intervention for Chinese schizophrenia sufferers.
How the Powerful Decide: Access to Research Participation by those at the Margins
Authors: McDonald Katherine E. , Keys Christopher B.
Published: June 2008

How do those in power decide to include and exclude those at the margins from community life? We used simulated review of research vignettes to examine how researchers and members of Institutional Review Boards make decisions concerning the research participation of adults with and without intellectual disabilities. Results indicate that decision‐makers are influenced by the disability status of the sample, characteristics of the research in which they are engaged, and their attitudes toward the research participation of adults with intellectual disabilities as well as their own relationship to the research process. For example, decision‐makers may create situations that limit the self‐determination of adults with intellectual disabilities and adults without disabilities within the research context, particularly when the research poses some risk of harm to participants. Implications for theory, action and research are explored.
Chemical Composition and Oxidative Stability of Kernel Oils from Two Current Subspecies of Pistacia atlantica in Iran
Authors: Farhoosh Reza , Tavakoli Javad , Khodaparast Mohammad Hossein Haddad
Published: June 2008

Pistacia atlantica subsp. mutica (PAM) and kurdica (PAK) kernel oils showed significantly lower unsaturated to saturated fatty acid ratios (6.39, 6.33, respectively) and calculated oxidizability (Cox) values (3.99, 4.13, respectively) than those of the P. vera L. cv. Ohadi (PVO) kernel oil (8.91, 4.41) samples. The highest peroxide value was observed for the PAK oil (4.07 mequiv kg−1) (PAM, 1.94; PVO, 0.37) samples. Iodine values for the PAM, PAK, and PVO oils were 104.26, 104.77, and 110.66, respectively. The saponification number of the PVO oil was significantly greater than the PAM and PAK oils, which were statistically not different. The unsaponifiable contents, which were composed mainly of sterols, ranged from 5.63 to 6.14%. Statistically the total tocopherols contents of the PAM (818.58 mg α‐tocopherol kg−1) and PVO (815.90 mg α‐tocopherol kg−1) oils were significantly higher than that of the PAK oil (499.91 mg α‐tocopherol kg−1). Total phenolics contents differed significantly, the greatest concentration was for the PAM oil (81.12 mg gallic acid kg−1), followed by the PVO (62.84 mg gallic acid kg−1) and PAK (56.51 mg gallic acid kg−1) oil samples. The wax contents of the oil samples were statistically in the same range, namely 5.67–6.48%. Oxidative stability data indicated that the PAM oil is the most resistant to the formation of lipid oxidation products, followed by the PAK and PVO oil samples.
Genetik und Klinik der Hämophilie A und B
Authors: Schwaab R. , Rost S. , Schröder J. , Müller-Reible C.R. , Oldenburg J.
Published: June 2008

Die Hämophilie A und B werden durch unterschiedliche Mutationen im Faktor VIII (FVIII)- bzw. Faktor IX (FIX)-Gen verursacht. Entsprechend der Schwere des molekularen Defekts gibt es klinisch unterschiedlich schwere Verlaufsformen der Erkrankung. Hämophiliepatienten können heutzutage ausgezeichnet mit aus Plasma oder rekombinant hergestellten Gerinnungspräparaten behandelt werden. Hierdurch können Blutungen und deren Folgen weitgehend verhindert werden, mit einer inzwischen fast normalisierten Lebensqualität und Lebenserwartung. Eine schwere Komplikation ist die Antikörper (Hemmkörper)-Bildung gegen den zugeführten Gerinnungsfaktor. Das Risiko einer solchen Hemmkörperbildung ist bei Vorliegen von Mutationen ohne endogene Faktor-VIII-Protein-Bildung besonders hoch und liegt bei 25–50%. Die Information über den zu erwartenden klinischen Verlauf ist heute die wichtigste Indikation für die FVIII-/FIX-Genanalyse und wird regelhaft bei den schwer betroffenen Hämophiliepatienten durchgeführt. Die Kenntnis des FVIII-/FIX-Gendefekts ermöglicht des Weiteren eine sichere und schnelle Überträgerinnendiagnose bei weiblichen Familienangehörigen von Hämophilen.
A proteomic study of the effects of ramipril on post‐infarction left ventricular remodelling in the rabbit
Authors: Chen Ching‐Yi , Lee Bai‐Chin , Hsu Hsiu‐Ching , Lin Hung‐Ju , Chao Chia‐Lun , Lin Yen‐Hung , Ho Yi‐Lwun , Chen Ming‐Fong
Published: June 2008

Objectives:

In this study, we used a proteomic approach to investigate the potential proteins regulated by ramipril in post‐infarction left ventricular remodelling in the rabbit.

Methods and results:

Myocardial infarction (MI) was induced in male New Zealand White rabbits (2.5–3 kg) by ligation of the left anterior descending coronary artery. Two months later, the rabbits were either left untreated (MI group) or were treated daily for one month with 0.1 mg/kg wt of ramipril (ramipril group), then sacrificed. One month of ramipril treatment resulted in a significant improvement in the LV ejection fraction (LVEF) and a decrease in hydroxyproline content. The protein profiles of LV tissue showed that ramipril caused upregulation of glutathione peroxidase, superoxide dismutase (SOD), and heart‐type fatty acid binding‐protein (h‐FABP) and downregulation of HSP27 and cyclophilin A. Ramipril treatment caused an increase in catalase, glutathione peroxidase, and SOD activity in the LV tissue. Oxidized glutathione levels and the GSSG/GSH ratio in the heart tissue were lower in the ramipril group than in the MI group.

Conclusions:

Ramipril increased antioxidative protein expression and enzyme activity, which could partly explain the role of ramipril in attenuating LV remodelling. In addition, the present study identifies several potential protein targets which may help to explain the mechanism by which ramipril exerts its effect in post‐infarction LV remodelling in the rabbit.
A roadmap to disentangle the molecular etiology of schizophrenia
Authors: Falkai Peter , Mike Owen , Inez Myin-Germeys , Paul Harrison , Andras Bilkei-Gorzo , Sophia Frangou ,   MEOS Consortium
Published: June 2008

Schizophrenia is a severe mental disorder striking mainly young adults and leading to life-long disability in a substantial portion of the sufferers. On the other hand, substantial knowledge about its etiology and pathogenesis is still lacking. Therefore the European Science Foundation (ESF) sponsored a meeting of a panel of European experts on schizophrenia research to discuss the state of art and future perspectives of key topics in this area. The fields covered genetics, epidemiology, animal models, molecular neuropathology and imaging. This was a first step to establish a network of European groups dedicated to Schizophrenia research. The coming calls of the frame work program will be used to strengthen this network in order to achieve substantial progress in understanding and treating this devastating illness.
Impact of the WHO depression guideline on patient care by psychiatrists: A randomized controlled trial
Authors: Linden Michel , Westram Anja , Schmidt Lutz G. , Haag Clemenz
Published: June 2008

Background

Scientific literature reviews aim to summarize the state of knowledge and published empirical evidence. In contrast, medical guidelines are intervention tools that aim to improve physician behaviour and patient outcome. They can have positive effects, but they can also have negative effects. Their effects must be tested by research.

Methods

In a randomized controlled trial, 103 psychiatrists in private practice were either provided with the WHO depression guideline only (information group), or provided with the WHO depression guideline and trained for one day in this guideline (intervention group), or left uninformed (control group). They then treated a total of 497 patients according to individual clinical considerations and the needs of the patients. Observation of routine treatment lasted 12 weeks. Physicians and patients documented the course of illness and treatment, including the patient–physician interaction.

Results

Psychiatrists in the intervention group saw more psychosocial stressors in their patients, prescribed higher dosages of medication, had fewer drop-outs, and rated treatment outcome as better. The ratings of patient–physician interactions indicated more strain in their relationships.

Conclusions

The results show both positive and negative effects of guideline exposure, but only in the training group and not in the information group. Guidelines should be empirically tested before being called “evidence based”. Every guideline should also explain how it can or must be implemented in order to become effective.
TAAR6variation effect on clinic presentation and outcome in a sample of schizophrenic in-patients: An open label study
Authors: Pae Chi-Un , Drago Antonio , Kim Jung-Jin , Patkar Ashwin A. , Jun Tae-Youn , Lee Chul , Mandelli Laura , De Ronchi Diana , Paik In-Ho , Serretti Alessandro
Published: June 2008

We recently reported an association betweenTAAR6(trace amine associated receptor 6 gene) variations and schizophrenia (SZ). We now report an association of a set ofTAAR6variations and clinical presentation and outcome in a sample of 240 SZ Korean patients. Patients were selected by a Structured Clinical Interview, DSM-IV Axis I disorders – Clinical Version (SCID-CV). Other psychiatric or neurologic disorders, as well as medical diseases, were exclusion criteria. To assess symptom severity, patients were administered the CGI scale and the PANSS at baseline and at the moment of discharge, 1 month later on average.TAAR6variations rs6903874, rs7452939, rs8192625 and rs4305745 were investigated; rs6903874, rs7452939 and rs8192625 entered the statistical investigation after LD analysis. Rs8192625 G/G homozygosis was found to be significantly associated both with a worse clinical presentation at PANSS total and positive scores and with a shorter period of illness before hospitalization. No haplotype significant findings were found. The present study stands for a role of theTAAR6in the clinical presentation of SZ. Moreover, our results show that this genetic effect may be counteracted by a correct treatment. Haplotype analysis was not informative in our sample, probably also because of the incomplete SNPs' coverage of the gene we performed. Further studies in this direction are warranted.
Specificity of Arl2/Arl3 signaling is mediated by a ternary Arl3‐effector‐GAP complex
Authors: Veltel Stefan , Kravchenko Aleksandra , Ismail Shehab , Wittinghofer Alfred
Published: June 2008

MINT‐6602303:

ARL2 (uniprotkb:P36404) binds (MI:0407) to HRG4 (uniprotkb:Q13432) by pull down (MI:0096)

MINT‐6602333:

ARL3 (uniprotkb:P36405) binds (MI:0407) to CoD (uniprotkb:Q9BTW9) by pull down (MI:0096)

MINT‐6602347, MINT‐6602369:

RP2 (uniprotkb:O75695), ARL3 (uniprotkb:P36405) and HRG4 (uniprotkb:Q13432) physically interact (MI:0218) by fluorescence polarization spectroscopy (MI:0053)

MINT‐6602195:

PDE delta (uniprotkb:O43924) and ARL2 (uniprotkb:P36404) bind (MI:0407) by fluorescence polarization spectroscopy (MI:0053)

MINT‐6602213:

BART (uniprotkb:Q8WZ55) and ARL2 (uniprotkb:P36404) bind (MI:0407) by fluorescence polarization spectroscopy (MI:0053)

MINT‐6602239:

ARL3 (uniprotkb:P36405) and BART (uniprotkb:Q8WZ55) bind (MI:0407) by fluorescence polarization spectroscopy (MI:0053)

MINT‐6602322:

ARL2 (uniprotkb:P36404) binds (MI:0407) to CoD (uniprotkb:Q9BTW9) by pull down (MI:0096)

MINT‐6602258:

RP2 (uniprotkb:Q8IWN7) and ARL3 (uniprotkb:P36405) bind (MI:0407) by fluorescence polarization spectroscopy (MI:0053)

MINT‐6602233:

ARL3 (uniprotkb:P36405) and HRG4 (uniprotkb:Q13432) bind (MI:0407) by fluorescence polarization spectroscopy (MI:0053)

MINT‐6602360:

HRG4 (uniprotkb:Q13432), ARL3 (uniprotkb:P36405) and RP2 (uniprotkb:O75695) physically interact (MI:0218) by molecular sieving (MI:0071)

MINT‐6602297:

ARL2 (uniprotkb:P36404) binds (MI:0407) to PDE delta (uniprotkb:O43924) by pull down (MI:0096)

MINT‐6602227:

ARL3 (uniprotkb:P36405) and PDE delta (uniprotkb:O43924) bind (MI:0407) by fluorescence polarization spectroscopy (MI:0053)

MINT‐6602204:

HRG4 (uniprotkb:Q13432) and ARL2 (uniprotkb:P36404) bind (MI:0407) by fluorescence polarization spectroscopy (MI:0053)
Multi‐site substrate binding and interplay in barley α‐amylase 1
Authors: Nielsen Morten Munch , Seo Eun-Seong , Bozonnet Sophie , Aghajari Nushin , Robert Xavier , Haser Richard , Svensson Birte
Published: June 2008

Certain starch hydrolases possess secondary carbohydrate binding sites outside of the active site, suggesting that multi‐site substrate interactions are functionally significant. In barley α‐amylase both Tyr380, situated on a remote non‐catalytic domain, and Tyr105 in subsite −6 of the active site cleft are principal carbohydrate binding residues. The dual active site/secondary site mutants Y105A/Y380A and Y105A/Y380M show that each of Tyr380 and Tyr105 is important, albeit not essential for binding, degradation, and multiple attack on polysaccharides, while Tyr105 predominates in oligosaccharide hydrolysis. Additional delicate structure/function relationships of the secondary site are uncovered using Y380A/H395A, Y380A, and H395A AMY1 mutants.
N‐Glycosylation of the Drosophila neural protein Chaoptin is essential for its stability, cell surface transport and adhesive activity
Authors: Hirai-Fujita Yu , Yamamoto-Hino Miki , Kanie Osamu , Goto Satoshi
Published: June 2008

Glycosylation of proteins can modulate their function in a striking variety of systems, including immune responses, neuronal activities and development. The Drosophila protein, Chaoptin (Chp), is essential for the development and maintenance of photoreceptor cells. This protein is heavily glycosylated, but the possible role of this glycosylation is not well‐understood. Here we show that mutations introduced into about 1/3 of 16 potential N‐linked glycosylation sites within Chp impaired its cell adhesive activities when expressed in Drosophila S2 cells. Mutation of 2/3 of the glycosylation sites resulted in a marked decrease in Chp protein abundance. These results suggest that N‐linked glycosylation of Chp is essential for its stability and activity.
Stria vascularis and vestibular dark cells: characterisation of main structures responsible for inner-ear homeostasis, and their pathophysiological relations
Authors: Ciuman R R
Published: June 2008

The regulation of inner-ear fluid homeostasis, with its parameters volume, concentration, osmolarity and pressure, is the basis for adequate response to stimulation. Many structures are involved in the complex process of inner-ear homeostasis. The stria vascularis and vestibular dark cells are the two main structures responsible for endolymph secretion, and possess many similarities. The characteristics of these structures are the basis for regulation of inner-ear homeostasis, while impaired function is related to various diseases. Their distinct morphology and function are described, and related to current knowledge of associated inner-ear diseases. Further research on the distinct function and regulation of these structures is necessary in order to develop future clinical interventions.
Giant petrous carotid aneurysm: persistent epistaxis despite internal carotid artery ligation
Authors: Singh H , Thomas J , Hoe W L E , Sethi D S
Published: June 2008

Objectives:

We report a rare case of giant petrous carotid aneurysm.

Method:

Case report and a review of the literature regarding treatment options for such aneurysms.

Results:

A 30-year-old man presented with epistaxis, headaches and visual disturbance. Definitive diagnosis was achieved by non-invasive imaging techniques, including magnetic resonance angiography and carotid angiography. Carotid angiography demonstrated a giant petrous carotid aneurysm effacing the petrous apex. The aneurysm was obliterated by internal carotid artery ligation, following successful tolerance of the balloon occlusion test. However, despite internal carotid artery ligation, this patient continued to have minor episodes of epistaxis.

Conclusion:

Some aneurysms are too large to be treated with endovascular occlusion techniques; in such cases, ligation of the parent vessel is indicated. However, our patient continued to experience persistent, mild epistaxis despite internal carotid artery ligation, as a result of the reperfusion phenomenon.
High frequency of heterozygosity in GJB2 mutations among patients with non-syndromic hearing loss
Authors: Khandelwal G , Bhalla S , Khullar M , Panda N K
Published: June 2008

Objective:

To determine the prevalence of GJB2 mutations among subjects with congenital, non-syndromic, sensorineural hearing loss, within a north Indian population.

Materials and methods:

This was a case–control study in which the frequencies of the three most prevalent GJB2 mutations (35delG, W24X and 167delT) were studied. Polymerase chain reaction restriction fragment length polymorphism assays were performed to detect these mutations. The entire coding region of the GJB2 gene was sequenced in all patients, and also in any of their family members who showed GJB2 mutations.

Results:

The 35delG mutation was found to be the most prevalent mutation (21 per cent), followed by the W24X mutation (7 per cent). This is the first report of the 35delG mutation in an Indian population. One patient was a compound heterozygote for 35delG/W24X. The 167delT mutation was not observed in any patient.

Conclusions:

These findings challenge the classical view that the W24X variant of the GJB2 gene represents a single ‘founder’ mutation.
Prevention of aspiration following recurrent dislodgement of voice prosthesis: a patient's innovation
Authors: Masaany M , Marina M B , Asma A , Sani A
Published: June 2008

Objective:

To demonstrate a simple, practical, cheap method of preventing potentially fatal aspiration of a dislodged voice prosthesis; this method was developed by a laryngectomised patient.

Case report:

A patient diagnosed with squamous cell carcinoma of the larynx underwent total laryngectomy. Upon completion of radiotherapy, a tracheoesophageal fistula was created and a voice prosthesis inserted to enable voice restoration. Unfortunately, the patient presented subsequently with repeated episodes of dislodgement and an episode of potentially fatal aspiration of the voice prosthesis, despite various measures taken by the surgeons to overcome the problem. The patient subsequently developed a method enabling him to retrieve the voice prosthesis himself should it become dislodged. He attached a ring to the prosthesis, which was larger in diameter than the tracheal stoma, thus preventing ingestion or recurrence of aspiration.

Conclusion:

To our knowledge, this is the first report in the world literature of this form of innovation, created by a laryngectomised patient, to overcome the problem of aspiration or ingestion of a dislodged voice prosthesis.
Rehabilitation after acute vestibular disorders
Authors: Teggi R , Caldirola D , Fabiano B , Recanati P , Bussi M
Published: June 2008

Objectives:

To assess the efficacy of rehabilitation for dizzy patients after recent acute vestibular disturbance.

Methods:

Forty patients recently hospitalised for an acute episode of rotational vertigo which lasted days were randomly divided into two groups. The first group (20 patients; group R) underwent active rehabilitation, while the second group (20 patients; group C) were told only to ‘perform their daily activities’. Group R subjects underwent a total of 10 sessions of rehabilitation, including exercises on a stabilometric platform, point de mire and a series of five exercises repeated five times daily. All patients performed static stabilometry (posturography), undertook the dynamic gait index test, and completed a dizziness handicap questionnaire and a visual analogue scale for anxiety, at baseline and on completion.

Results:

At 25 days, the rehabilitated patients obtained better results for all recorded outcomes, compared with the control group. The greatest difference in the rehabilitated subjects, compared with the control group, was for the dynamic gait index test; however, this difference was not statistically significant. The visual analogue scale anxiety score was statistically significantly more reduced in rehabilitated patients compared with control patients. Control patients maintained a higher visual dependence for postural control.

Conclusions:

These results would appear to support the effectiveness of a supervised exercise programme for patients following acute onset of vestibular disturbance. A correlation was found in both groups between dynamic gait index results and anxiety. In our experience, a rehabilitation programme seems to reduce dependence on visual cues for postural control.