bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of the β3 adrenoceptor agonist CL 316243 on hypothalamic 5-HT synthesis and suppression of REM sleep in the rat
Authors: Conley R.K. , Li J. , Ivarsson M. , Hutson P.H.
Published: November 2006

β3 adrenoceptor agonists show an antidepressant-like profile in preclinical rodent assays and improve mood in clinically-obese patients. These observations suggest a possible antidepressant utility for β3 adrenoceptor agonists. The present study examined the effects of acute and chronic administration of the β3 adrenoceptor agonist CL 316243 on two physiological indicators of antidepressant activity in the rat: hypothalamic 5-HT synthesis and suppression of REM sleep. 5-HT synthesis was estimated by the accumulation of 5-hydroxytryptophan (5-HTP) after treatment with the L-aromatic acid decarboxylase inhibitor NSD 1015. Sleep-wake patterns were monitored using electroencephalogram and electromyogram signals collected by radiotelemetry. Rats were administered CL 316243 acutely or once daily for 11 days. Acute administration of CL 316243 significantly increased hypothalamic 5-HT synthesis, as indicated by increased levels of 5-HTP, and reduced the amount of REM sleep. However, chronic administration produced no changes in 5-HTP or REM compared with vehicle treatment. The present observations suggest that acute administration of CL 316243 causes antidepressant-like effects on REM sleep, possibly mediated by increased central 5-HT synthesis. However, these effects are not maintained with repeated dosing.
The smoking Stroop and delay discounting in smokers: effects of environmental smoking cues
Authors: Field Matt , Rush Michelle , Cole Jon , Goudie Andrew
Published: November 2006

We investigated the effects of exposure to environmental smoking-related cues (holding a lit cigarette in an environment previously associated with smoking) on cigarette craving, colour naming of smoking-related words in a modified Stroop task, and on the delay discounting of hypothetical rewards, in daily cigarette smokers (N = 30). Compared to exposure to neutral cues, exposure to smoking-related cues was associated with increased cigarette craving and slower colour naming of smoking-related compared to matched control words. However, smoking cues had no effect on delay discounting. These results suggest that smoking cues increase craving and the ability of smoking-related words to grab the attention, but do not influence impulsive decision-making. Theoretical and clinical implications are discussed.
Comparison of diphenhydramine and modafinil on arousal and autonomic functions in healthy volunteers
Authors: Hou R.H. , Langley R.W. , Szabadi E. , Bradshaw C.M.
Published: November 2006

Arousal is regulated by the interplay between wakefulness- and sleep-promoting nuclei. Major wakefulness-promoting nuclei are the histaminergic tuberomamillary nucleus (TMN) of the hypothalamus and the noradrenergic locus coeruleus (LC) of the pons, which also play a role in autonomic regulation. First generation antihistamines, such as diphenhydramine, are likely to cause sedation by blocking excitatory H1 histamine receptors in the cerebral cortex, and the anti-narcolepsy drug modafinil may promote wakefulness by activating the locus coeruleus. We compared the effects of single doses of diphenhydramine (75 mg) and modafinil (200 mg) on arousal and autonomic functions in 16 healthy male volunteers, using a placebo-controlled, balanced, double-blind design. Arousal was assessed by critical flicker fusion frequency (CFFF), visual analogue scales (VAS) and pupillary fatigue waves (Pupillographic Sleepiness Test (PST)). Autonomic functions measured included resting pupil diameter, light and darkness reflex responses, blood pressure, heart rate and salivation. Data were analysed with ANOVA, with multiple comparisons. Diphenhydramine had sedative effects as shown by reductions in CFFF, VAS alertness ratings and increases of the indices of pupillary fatigue. Modafinil had alerting effects as indicated by reductions in the measures of pupillary fatigue. Comparison of pre-post medication changes in pupil diameter showed a decrease after diphenhydramine and an increase after modafinil. Diphenhydramine reduced salivation, and modafinil increased systolic blood pressure. In conclusion, diphenhydramine and modafinil evoked opposite effects on arousal and sympathetic functions, which are likely to reflect their interaction with the central histaminergic and noradrenergic systems. Hyposalivation by diphenhydramine is likely to be due to its additional anticholinergic property.
Effectiveness of olanzapine in neurosyphilis related organic psychosis: a case report
Authors: Turan Senol , Emul Murat , Duran Alaattin , Mert Ali , Uğur Mufit
Published: November 2006

The clinicians usually do not consider syphilis in the differential diagnosis for patients with acute and chronic psychiatric symptoms. To familiarize clinicians particularly with neurosyphilis (NS) and to discuss the atypical antipsychotic alternatives, we wish to present a case with agitated, resistant psychotic symptoms related to neurosyphilis. The case was a 55-year-old male who has had anxiety, irritability, auditory hallucinations, ataxia, dysarthric speech, paranoid and persecutory delusions and agitated behaviour. Parenteral ziprasidone 20 mg/bid was initialized at the first day of admission to reduce agitation. Then it was switched to olanzapine velotab 10 mg/bid because of inefficacy. Parenteral cephtriaxon 1 g/daily was administered because of seropositive VDRl and TPHA and positive cerebrospinal fluid VDRl. Olanzapine velotab may be a good alternative antipsychotic and should be considered in reducing agitation and psychotic symptoms in NS.
Review: Combination therapy with non-clozapine atypical antipsychotic medication: a review of current evidence
Authors: Chan Jenifer , Sweeting Melinda
Published: November 2006

Use of combined antipsychotics for patients with treatmentresistant/refractory schizophrenia is common practice in psychiatry. The objective of this paper is to review the current literature on combining non-clozapine atypical antipsychotics as well as discussing the theoretical benefits and risks, and summarizing the implications for clinical practice.

We found in cases of treatment-resistant schizophrenia, where clozapine is deemed inappropriate, combination therapy with non-clozapine atypical antipsychotics is a strategy worthy of consideration. Combinations using olanzapine with either amisulpride or risperidone — or quetiapine with risperidone — in theory act on different receptor profiles and in the limited data available have shown improvement in symptoms, been used most frequently, and on balance have more data on safety. Initial case reports suggest that aripiprazole combined with non-clozapine atypicals may worsen psychosis.

The current literature, however, has significant limitations. For this reason, due to the lack of data on safety, caution is recommended. There needs to be further well-designed studies with the aim to specifically investigate the effects of combination therapy to allow the clinician to better balance the risks and benefits (both clinical and economical) of treatment.
In vitro functional characteristics of dopamine D2 receptor partial agonists in second and third messenger-based assays of cloned human dopamine D2Long receptor signalling
Authors: Jordan Shaun , Regardie Karen , Johnson Janelle L. , Ruoyan Chen  , Kambayashi Junichi , McQuade Robert , Kitagawa Hisashi , Tadori Yoshihiro , Kikuchi Tetsuro
Published: November 2006

Aripiprazole, (+)terguride, OPC-4392 and (—)3-PPP have been classified as dopamine D2 receptor partial agonists based largely on their activity in second messenger-based assays of dopamine D2 receptor signalling. Nevertheless, signal transduction amplification might result in these compounds behaving as dopamine D2 receptor full agonists at a more downstream level of signalling. We compared the intrinsic activity (Emax, expressed as a percentage of the maximal effect of dopamine) of aripiprazole, (+)terguride, OPC-4392 and (—)3-PPP using second (calcium (Ca2+) mobilization) and third (extracellular signal-regulated kinase 2 (ERK2) phosphoprotein expression) messenger readouts of cloned human dopamine D2long (hD2L) receptor signalling in CHO cells. These compounds were all less potent and displayed lower intrinsic activity in the Ca2+ assay (aripiprazole = 24.3%, (+)terguride = 56.9%, OPC-4392 = 58.6% and (—)3-PPP = 75.1%), and aripiprazole (Emax = 54.5%) displayed a substantially lower intrinsic activity than (+)terguride (Emax = 92.3%), OPC-4392 (Emax = 93.1%) and (—)3-PPP (Emax = 101.1%) in the more downstream-based ERK2 phosphoprotein expression assay. These drug effects on Ca2+ mobilization and ERK2 phosphoprotein expression were mediated through dopamine hD2L receptors, as they all were blocked by (—)raclopride, whereas (—)raclopride and other dopamine D2 receptor antagonists (haloperidol, risperidone, ziprasidone, olanzapine, clozapine and quetiapine) were inactive on their own in both assays. These data are consistent with clinical evidence that only dopamine D2 receptor partial agonists with a sufficiently low enough intrinsic activity will prove effective against the positive symptoms of schizophrenia, and also highlight the importance of using downstream-based assays in the discovery of novel D2 receptor partial agonist therapeutics.
The G196A polymorphism of the brain-derived neurotrophic factor gene and the antidepressant effect of milnacipran and fluvoxamine
Authors: Yoshida Keizo , Higuchi Hisashi , Kamata Mitsuhiro , Takahashi Hitoshi , Inoue Kazuyuki , Suzuki Toshio , Itoh Kunihiko , Ozaki Norio
Published: November 2006

Prediction of the response to different classes of antidepressants has been an important matter of concern in the field of psychopharmacology. The purpose of the present study was to investigate whether the G196A polymorphism of the brain-derived neurotrophic factor (BDNF) gene is associated with the antidepressant effect of milnacipran, a serotonin norepinephrine reuptake inhibitor, and fluvoxamine, a selective serotonin reuptake inhibitor. The subjects of our previous study of milnacipran ( n = 80) and fluvoxamine ( n = 54) were included in the present study. Severity of depression was assessed with the Montgomery Åsberg depression rating scale (MADRS). Assessments were carried out at baseline and at 1, 2, 4 and 6 weeks of treatment. Polymerase chain reaction was used to determine allelic variants. In all subjects receiving milnacipran or fluvoxamine, the G/A genotype of the BDNF G196A polymorphism was associated with a significantly better therapeutic effect in the MADRS scores during this study. When milnacipran and fluvoxamine-treated subjects were analysed independently, the G/A genotype group showed greater reduction of MADRS scores than other genotype groups, irrespective of which antidepressant was administered. These results suggest that the BDNF G196A polymorphism in part determines the antidepressant effect of both milnacipran and fluvoxamine.
Association study of four dopamine D1 receptor gene polymorphisms and clozapine treatment response
Authors: Hwang Rudi , Shinkai Takahiro , De Luca Vincenzo , Xingqun Ni  , Potkin Steven G. , Lieberman Jeffrey A. , MeLtzer Herbert Y. , Kennedy James L.
Published: November 2006

Dopamine D1 receptors (D1) in the prefrontal cortex have been implicated in the modulation of cognitive processes as well as both positive and negative symptoms of schizophrenia. Therefore pharmacologic agents with potent D1 effects such as clozapine may influence the symptoms of schizophrenia (SCZ). Genetic variation in the D1 receptor gene ( DRD1) may help to explain some of the variability in patient response to antipsychotics (APs). This study investigates the effect of four single nucleotide polymorphisms (SNPs) in DRD1 on clozapine response in two distinct SCZ populations (Caucasian and African American) refractory or intolerant to conventional APs. This study included 183 Caucasian and 49 African American schizophrenics diagnosed using the Diagnostic and Statistical Manual of Mental Disorders (revised third or fourth edition). Genotyping was determined by 5'-exonuclease fluorescence assays. Within each population genotype, allele, allele +/— and haplotype frequencies were compared against dichotomous and quantitative measures of treatment response. Linkage disequilibrium analysis was also performed. In the Caucasian sample, no associations were observed for individual SNP tests. However, a rare three-marker haplotype predicted poor response. In the African American sample, the rs265976 variant and another three-marker haplotype were associated with cLozapine response. Although we did not find an association between the rs4532 SNP (—48 A/G, recognized by a DdeI restriction cut site) and cLozapine response as reported by Potkin et al. (2003), a trend in the same direction was observed as well. Our findings suggest that the rs4532 SNP may have a small effect if any. Further studies in larger, independent samples are required to validate these findings.
Selective verbal and spatial memory impairment after 5-HT1A and 5-HT2A receptor blockade in healthy volunteers pre-treated with an SSRI
Authors: Wingen M. , Kuypers K.P.C. , Ramaekers J.G.
Published: November 2006

Serotonergic neurotransmission has been implicated in memory impairment. It is uncLear however if memory performance is mediated through general 5-HT availability, through specific 5-HT receptors or both. The aim of the present study was to assess the contribution of 5-HT reuptake inhibition and specific blockade of 5-HT1A and 5-HT2A receptors to memory impairment.

The study was conducted according to a randomized, double-blind, placebo-controlled, four-way cross-over design including 16 healthy volunteers. The treatment consisted of oral administration of escitalopram 20 mg + placebo, escitalopram 20 mg + ketanserin 50 mg, escitalopram 20 mg + pindolol 10 mg and placebo on 4 separate days with a washout period of minimum 7 days. Different memory tasks were performed including verbal memory, spatial working memory and reversal learning.

Escitalopram showed an impairing effect on immediate verbal recall which nearly reached statistical significance. No effects of escitalopram were found on other types of memory. In combination with pindolol, immediate verbal recall was significantly impaired. Escitalopram in combination with ketanserin impaired spatial working memory significantly. No effects were found on reversal learning.

Selective impairment of immediate verbal recall after a 5-HT1A partial agonist and selective impairment of spatial working memory performance after 5-HT2A receptor antagonist, both in combination with a selective serotonergic reuptake inhibitor (escitalopram), suggests that 5-HT1A and 5-HT2A receptors are distinctly involved in verbal and spatial memory.
Association study of olanzapine-induced weight gain and therapeutic response with SERT gene polymorphisms in female schizophrenic patients
Authors: Bozina Nada , Medved Vesna , Kuzman Martina Rojnic , Sain Ivica , Sertic Jadranka
Published: November 2006

We investigated the relationships between L/S promoter (SERTPR) and l/s intron2 (SERTin2) genetic variants of serotonin transporter (SERT) polymorphisms with olanzapine-induced weight gain and treatment response in 94 female schizophrenic patients treated with olanzapine for up to 3 months. Body mass index (BMI) was calculated for each patient prior to olanzapine administration and 3 months afterwards. To assess and evaluate improvement of clinical psychotic symptoms and therapeutic response to the antipsychotic, all patients were rated using the Positive and Negative Syndrome ScaLe (PANSS). Overall, the presence of S SERTPR allelic variant and SS genotype was associated with significantly higher weight gain in subjects who were non-obese at the time of admission. The presence of L SERTPR variant was associated with significantly better treatment response measured with total PANSS and general PANSS subscale, while the presence of l SERTin2 variant determined better treatment response only in several items. No evidence of linkage disequilibrium between the two loci was found in the sample. These findings identify genetic factors associated with oLanzapine-induced weight gain and treatment response in femaLe schizophrenic patients.
Evidence-based guidelines for management of attention-deficit/hyperactivity disorder in adolescents in transition to adult services and in adults: recommendations from the British Association for Psychopharmacology
Authors: Nutt D. J. , Fone K. , Asherson P. , Bramble D. , Hill P. , Matthews K. , Morris K. A. , Santosh P. , Sonuga-Barke E. , Taylor E. , Weiss M. , Young S.
Published: November 2006

Attention-deficit/hyperactivity disorder (ADHD) is an established diagnosis in children, associated with a large body of evidence on the benefits of treatment. Adolescents with ADHD are now leaving children’s services often with no readily identifiable adult service to support them, which presents problems as local pharmacy regulations often preclude the prescription of stimulant drugs by general practitioners (GPs). In addition, adults with ADHD symptoms are now starting to present to primary care and psychiatry services requesting assessment and treatment. For these reasons, the British Association for Psychopharmacology (BAP) thought it timely to hold a consensus conference to review the body of evidence on childhood ADHD and the growing literature on ADHD in older age groups. Much of this initial guidance on managing ADHD in adolescents in transition and in adults is based on expert opinion derived from childhood evidence. We hope that, by the time these guidelines are updated, much evidence will be available to address the many directions for future research that are detailed here.
Citalopram-induced SIADH in a hypertensive patient on salt restricted diet
Authors: Bez Yasin , Aktolga Serdal , Balci Merih , Nurmedov Serdar , Topçuoglu Volkan
Published: November 2006

Hyponatraemia is a very rare but potentially fatal complication of SSRIs and citalopram therapy, especially during the first weeks of treatment and for those who concomitantly use medications known to cause hyponatraemia. We present a 54-year-old hypertensive female patient who was admitted to the hospital with drowsiness, paresthesia, fatigue, nausea, vomiting and visual hallucinations and who was diagnosed to have syndrome of inappropriate secretion of antidiuretic hormone (SIADH) due to citalopram. All her presenting symptoms disappeared after discontinuation of citalopram therapy, fluid restriction and a careful hypertonic saline infusion. This case suggests that SIADH may develop among hypertensive patients, especially when they use diuretics or follow a salt restricted diet.
Considering the Role of the University in Conducting Research on Agri-biotechnologies
Authors: Welsh Rick , Glenna Leland
Published: November 2006

Private sector firms have dominated the research, development, and commercialization processes for transgenic crops. This has led to a narrow focus on a few commercially important crops and engineered traits, while minor crops and traits remain largely ignored. Analysts have decried this situation and called for more public-centered research regimes, such as research on minor crops and traits. Universities are often identified as places where research on the more minor crops and traits should occur. The burgeoning literature on the changing structure of the university toward an institution more aligned with private for-profit sector interests and orientations calls these arguments into question. Using time series data from 1993-2002 obtained from the US Department of Agriculture’s Animal and Plant Health Inspection Service, we find that over time, university research on transgenic crops has increasingly mirrored the research profile of for-profit firms.
Classifying Microorganisms:
Authors: Sommerlund Julie
Published: November 2006

This paper describes the coexistence of two systems for classifying organisms and species: a dominant genetic system and an older naturalist system. The former classifies species and traces their evolution on the basis of genetic characteristics, while the latter employs physiological characteristics. The coexistence of the classification systems does not lead to a conflict between them. Rather, the systems seem to co-exist in different configurations, through which they are complementary, contradictory and inclusive in different situations-sometimes simultaneously. The systems come into conflict only through the researchers’ verbal articulations; in their application conflict is hardly present at all. This paper treats their relationship as the ’central tension of science’ in reverse. Rather than comprising heterogeneous communities that need boundary objects to make cooperation and integration possible, the field of molecular biology seems to be overwhelmingly homogeneous, and in need of heterogeneity and conflict to add drive and momentum to the work being carried out. The paper is based on observations of daily life in a molecular microbiology laboratory at the Technical University of Denmark. It is thus a ’real time’ and material study of scientific paradigms and discourses.
Effects of Local Administration of Vascular Endothelial Growth Factor on Mechanical Characteristics of the Semitendinosus Tendon Graft after Anterior Cruciate Ligament Reconstruction in Sheep
Authors: Yoshikawa Toshikazu , Tohyama Harukazu , Katsura Taro , Kondo Eiji , Kotani Yoshihisa , Matsumoto Hideo , Toyama Yoshiaki , Yasuda Kazunori
Published: November 2006

Background

Vascular endothelial growth factor (VEGF) is a potent mediator of angiogenesis.

Hypothesis

An application of VEGF may enhance angiogenesis in the grafted tendon in anterior cruciate ligament (ACL) reconstruction, and the application may affect mechanical characteristics of the ACL graft.

Study Design

Controlled laboratory study.

Methods

Eighteen sheep were divided into groups I and II. In group I, the harvested semitendinosus tendon was soaked in VEGF solution, and the right knee then underwent ACL reconstruction using this tendon. In group II, the right knee underwent identical procedures to those of group I except that the harvested tendon was soaked in phosphate-buffered saline. All animals were sacrificed 12 weeks after ACL reconstruction.

Results

Histologic findings showed that newly formed vessels and infiltrative fibroblasts were more abundant in group I than in group II. The anterior-posterior translation of the knee during an anterior-posterior force of ±100 N was significantly larger in group I than in group II by 2.58 mm (95% confidence interval, -1.76 mm to 1.76 mm) (P =. 002). The linear stiffness of the femur-graft-tibia complex in group I was significantly lower than that in group II by 41.5 N/mm (95% confidence interval, -32.2 N/mm to 32.2 N/mm) (P=. 017).

Conclusion

This study has revealed that VEGF as administered in this study promotes angiogenesis in the ACL graft and significantly reduces the stiffness of the ACL graft with increased knee laxity at 12 weeks after ACL reconstruction.

Clinical Relevance

Exogenous VEGF application for ACL reconstruction can induce an increase in knee laxity and a decrease in the stiffness of the grafted tendon at least temporarily after ACL reconstruction. These potentially negative mechanical effects need to be taken into account when considering clinical use of VEGF.
Unraveling Equity in HOT Lane Planning
Authors: Weinstein Asha , Sciara Gian-Claudia
Published: November 2006

This article investigates how concern about equity has arisen in the planning and implementation of high-occupancy/toll lane projects, or so-called “HOT lanes.” Specifically, the research assesses (1) where and how equity issues have surfaced in the debate over HOT lanes and (2) how practicing planners have responded to these equity concerns. By looking explicitly at the planning process through a series of case studies and a review of newspaper coverage, the research suggests strategies for how practitioners can craft a comprehensive and meaningful framework for assessing and addressing equity issues.
Bottom-Up Planning and the Future of Planning Education in India
Authors: Chettiparamb Angelique
Published: November 2006

The article discusses normative guidelines for reorienting planning education in India within the context of the immensely influential Constitutional Amendment Act of 1993. First, it briefly sketches the status of planning education at present in India, in relation to the role of planners in planning practice. It then descibes the changes that have taken place in general, following the Constitutional Amendment Act, dwelling more on the specific changes within the State of Kerala. The implications of these for planning education in general are then discussed normatively, highlighting three areas that need immediate attention from the planning academic community.
Sustainability
Authors: Gunder Michael
Published: November 2006

This article explores the concept—sustainability—as a transcendental ideal of planning purpose and value. The article critically argues that sustainability largely has been captured and deployed under a narrative of sustainable development in a manner that stifles the potential for substantive social and environmental change, all of which constitutes new purpose, legitimacy, and authority for the discipline of planning and its practitioners while potentially sustaining or creating adverse social and environmental injustices. These are injustices that planning traditionally attempted to address but now often obscures under the primacy of the economic imperative within dominant institutional interpretations of the sustainable development narrative.
Terror, Barriers, and the Changing Topography of Jerusalem
Authors: Savitch H. V. , Garb Yaakov
Published: November 2006

This article deals with the impact of urban terror and the construction of a peripheral barrier around Jerusalem. We are interested in an atypical set of conditions, or what might be called punctuated change, characterized by (1) an extremely shortened or telescoped time span; (2) the presence of an abrupt crisis that threatens to seriously harm, negatively transform, or even destroy a social order; (3) a volatile environment in which response is unpredictable; and (4) a set of presumed solutions whose efficacy or effects are unknown. On the Israeli side, we find that terrorism has contributed to an existing momentum of decentralization and accelerated a declining city center. On the Palestinian side, the construction of the Jerusalem barrier has changed the shape of the metropolitan area, separating neighborhoods from one another and some from the rest of the city. Together, terror and barriers are changing the topography of metropolitan Jerusalem.
A Survey of Undergraduate Course Syllabi and a Hybrid Course on Global Urban Topics
Authors: Ali Amal K. , Doan Petra L.
Published: November 2006

In recent years, many planning departments at American universities have begun to teach introductory world-cities courses at the undergraduate level. This trend is explained by the growing recognition of the role and importance of undergraduate planning education, increasing interests in effects of globalization on cities, and pressures from university administrators for planning faculty to increase enrollment. This article reviews strategies adopted to teach world cities to undergraduate students. It presents insights from several sources: a content analysis of forty-three world-cities syllabi, a survey of instructors whose syllabi were analyzed, and the experience of one of the authors in teaching a hybrid course in world cities in which part of the course was taught online and another in class. The study findings provide useful suggestions for instructors, departments, and universities interested in innovative approaches to teach undergraduate courses in global urban topics.
Student Experiences of Work-Based Learning in Planning Education
Authors: Freestone Robert , Thompson Susan , Williams Peter
Published: November 2006

Of various approaches to teaching planning in practice, work-based or integrated learning retains vital relevance in many planning programs. There are strong rationales in pedagogic, professional development, employment, and personal terms. But what of student experiences of work experience? How do student planners approach, experience, and reflect on workplace engagements? This article explores these experiential dimensions through a survey of a cohort of Australian students involved in a yearlong paid placement as part of an accredited undergraduate planning degree. It discusses the changing expectations of students and whether these were realized, their major learning experiences, and an overall evaluation of off-campus learning. The findings have wider relevance for evaluating student assessments of work-based learning in planning education.
Haptics in computer-mediated simulation: Training in vertebroplasty surgery
Authors: Chui Chee-Kong , Ong Jackson S. K. , Lian Zheng-Yi , Wang Zhenlan , Teo Jeremy , Zhang Jing , Yan Chye-Hwang , Ong Sim-Heng , Wang Shih-Chang , Wong Hee-Kit , Teo Chee-Leong , Teoh Swee-Hin
Published: November 2006

Surgical simulators and computer games share the enabling technologies in the human-machine interface. With appropriate design and development, the computer-game-like medical training simulator could be used in surgical training. The authors describe a PC-based system for the simulation of the vertebroplasty procedure. In vertebroplasty, the surgeon or radiologist relies on sight and feel to properly insert the bone needle through various tissue types and densities and monitor the injection and reflux of the polymethylmethacrylate (PMMA), or cement, into the vertebra. This article focuses on the provision of a near-realistic haptic feel in bone needle insertion and manual PMMA injection. This involves an efficient biomechanical modeling of bone needle insertion and PMMA flow in bone for haptic rendering, as well as reliable delivery of forces via haptic devices. The authors show that with virtual reality gaming technologies, the surgical simulator can become a virtual trainer for a potentially risky spinal interventional procedure.
Adapting COTS games for military experimentation
Authors: Fong Gwenda
Published: November 2006

The ease of modifying computer games renders them effective as low-cost virtual worlds that have found relevance in military experimentation. This article presents the Singapore Armed Forces’ (SAF) and the Defence Science & Technology Agency’s (DSTA) initiatives to leverage games for concept exploration. The SAF Centre for Military Experimentation conducted a gaming workshop in October 2004 to explore how soldiers could make use of information to alleviate the challenges in an urban warfare scenario. The workshop generated many insights into the issues surrounding information requirement and usage, sense making, and command and control. As the SAF’s technology partner, the DSTA is also seeking to illustrate the concept and value of integrated knowledge-centric systems through games. These initiatives represent the first steps in our commitment to explore and harness computer games in engaging our next generation of soldiers in the development of war-fighting concepts of the future.
Simulation-based problem-solving environments for conflict studies
Authors: Yilmaz Levent , Ören Tuncer I. , Ghasem-Aghaee Nasser
Published: November 2006

At the dawn of the 21st century, uncertainty, change, and conflicts are inescapable facts of life. The challenge is to explore how the advances in simulation gaming as reflected in its state-of-the-art as well as in its potential can be helpful for conflict and peace studies. This article presents the issues, challenges, and foundations underlying multimodels and the multisimulation gaming strategy. Taxonomy of multimodels and plausible multisimulation realization strategies are presented to contribute to the development of advanced simulation-based problem-solving environments for social and political scientists to improve their ability to conceive, perceive, and foresee conflicting situations to ideally prevent them and—if they are inevitable—to resolve them.
Immersive protein gaming for bio edutainment
Authors: Cai Yiyu , Lu Baifang , Zheng Jianmin , Li Lin
Published: November 2006

Games have long been used as a tool for teaching important subject matter, from concept building to problem solving. Through fun learning, students may further develop their curiosities and interest in their study. This article addresses the issue of learning biomolecular structures by virtual reality gaming. A bio edutainment solution featuring stereographic visualization, 3D modeling, and game interaction is developed for students to learn amino acids, α -helices, β -sheets, and other protein structure information. A pilot study is performed in this work with Singapore Chinese High School; initial results of this study are presented.
Real-time 3D video avatar in mixed reality: An implementation for immersive telecommunication
Authors: Lee Sang-Yup , Ahn Sang C. , Kim Hyoung-Gon , Lim MyoTaeg
Published: November 2006

This article presents an implementation of a real-time dynamic 3D avatar from multiview cameras for immersive telecommunication. Immersive telecommunication is a new challenging field that enables a user to share a virtual space with remote participants, providing users with a sense of telepresence and interaction. The main objective is to offer rich communication modalities, as similar as those used in face-to-face meetings, like gestures, gaze awareness, realistic images, and correct sound direction. As a result, the user can be immersed and has natural interaction with remote participants. This would overcome the limitations of conventional video-based telecommunication as well as the VR-based collaborative virtual environment approaches.
Simulating pattern design and layout for group calisthenics and eurhythmics
Authors: Pan Zhigeng , Ji Qingge , Zhang Mingmin , Li Yanfeng , Mei Lin
Published: November 2006

Virtual reality has been applied to many areas such as education, art, entertainment, engineering, and sports simulation. Two case studies for sports simulation are presented here: the simulation of pattern design for group calisthenics and the simulation of the layout for group eurhythmics (art gymnastics). Virtual human technique is employed in both simulation systems. In case study 1, the authors studied group calisthenics training simulation to reduce rehearsal time. Several path-planning methods and a collision avoidance algorithm are presented. The new algorithm is simpler and more efficient than former methods. The system can help group calisthenics arrangement personnel improve designing quality and efficiency of transforming of alignment and pattern. In case study 2, the authors design and implement a simulation system for the group eurhythmics layout. It provides a direct and convenient method to train athletes for the eurhythmics team coaches. Experimental results illustrate the efficiency of the prototype systems.
Participation and Political Competition in Committee Report Allocation
Authors: Hausemer Pierre
Published: November 2006

The paper models the consequences of committee report allocation for political representation in the European Parliament (EP). The range of legislators involved in each policy area affects the values, interests and constituencies that the Parliament represents. Thus, representation is defined as an MEP’s participation in salient policy areas. The allocation of salient reports follows inter-and intra-party group dynamics. First, party groups compete for salient reports in a context of open voting rules in committee and plenum. Second, group coordinators distribute these reports among their MEPs in an attempt to maximize the cohesion of the group. The model is tested on data from the fifth European Parliament (1999-2002). The results confirm the impact of selective participation on political representation. The EP has evolved into a ‘normal’ Parliament featuring coalitions and competition along a left-right cleavage across party groups and a hierarchical allocation of legislative spoils within parties.
Circulating proteasome levels are an independent prognostic factor for survival in multiple myeloma
Authors: Jakob Christian , Egerer Karl , Liebisch Peter , Türkmen Seval , Zavrski Ivana , Kuckelkorn Ulrike , Heider Ulrike , Kaiser Martin , Fleissner Claudia , Sterz Jan , Kleeberg Lorenz , Feist Eugen , Burmester Gerd-R. , Kloetzel Peter-M. , Sezer Orhan
Published: November 2006

The proteasome is a proteolytic complex for intracellular degradation of ubiquitinated proteins which are involved in cell-cycle regulation and apoptosis. A constitutively increased proteasome activity has been found in myeloma cells. We studied circulating proteasome levels and their prognostic significance in sera of 50 control subjects, 20 persons with monoclonal gammopathies of undetermined significance (MGUS), and 141 previously untreated patients with multiple myeloma (MM) by an anti-20S proteasome enzyme-linked immunoabsorbent assay (ELISA). Serum proteasome concentrations were significantly elevated in MM compared with controls (P < .001), in MM versus MGUS (P = .03), and in active (n = 101) versus smoldering (n = 40) MM (P < .001). In patients with active MM, there was a significant (P < .001) decrease from pretreatment to post-treatment proteasome concentrations in responders to chemotherapy, but not in nonresponders. Circulating proteasome levels were identified as a prognostic factor for overall survival in the univariate (P < .001 log-rank test) and in the multivariate (hazard ratio, 4.38) survival analysis in patients with active MM. We demonstrate for the first time that increased serum proteasome concentrations correlate with advanced disease and are an independent prognostic factor in MM.
Prognosis of children with acute lymphoblastic leukemia (ALL) and intrachromosomal amplification of chromosome 21 (iAMP21)
Authors: Moorman Anthony V. , Richards Susan M. , Robinson Hazel M. , Strefford Jon C. , Gibson Brenda E. S. , Kinsey Sally E. , Eden Tim O. B. , Vora Ajay J. , Mitchell Christopher D. , Harrison Christine J. ,   on behalf of the UK Medical Research Council (MRC)/National Cancer Research Institute (NCRI) Childhood Leukaemia Working Party (CLWP)
Published: November 2006

Patients with acute lymphoblastic leukemia (ALL) and an intrachromosomal amplification of chromosome 21 (iAMP21) comprise a novel and distinct biological subgroup. We prospectively screened 1630 (84%) patients treated on the UK MRC ALL97 protocol for iAMP21 and herein present demographic, clinical, and survival data on the 28 (2%) children found to harbor this abnormality. They had a common or pre-B ALL immunophenotype, were significantly older (median 9 years vs 5 years), and had a lower white cell count (median 3.9 vs 12.4) compared with children without this abnormality. Notably, patients with iAMP21 had a significantly inferior event-free and overall survival at 5 years compared with other patients: 29% (95% confidence interval [CI], 13%-48%) versus 78% (95% CI, 76%-80%) and 71% (95% CI, 51%-84%) versus 87% (95% CI, 85%-88%), respectively. As a result of this 3-fold increase in relapse risk, newly diagnosed patients with iAMP21 recruited to the current UK MRC ALL2003 trial are being treated on the high-risk arm and are considered for bone marrow transplantation in first remission.
DWARF – a data warehouse system for analyzing protein families
Authors: Fischer Markus , Thai Quan K , Grieb Melanie , Pleiss Jürgen
Published: November 2006

Background

The emerging field of integrative bioinformatics provides the tools to organize and systematically analyze vast amounts of highly diverse biological data and thus allows to gain a novel understanding of complex biological systems. The data warehouse DWARF applies integrative bioinformatics approaches to the analysis of large protein families.

Description

The data warehouse system DWARF integrates data on sequence, structure, and functional annotation for protein fold families. The underlying relational data model consists of three major sections representing entities related to the protein (biochemical function, source organism, classification to homologous families and superfamilies), the protein sequence (position-specific annotation, mutant information), and the protein structure (secondary structure information, superimposed tertiary structure). Tools for extracting, transforming and loading data from public available resources (ExPDB, GenBank, DSSP) are provided to populate the database. The data can be accessed by an interface for searching and browsing, and by analysis tools that operate on annotation, sequence, or structure. We applied DWARF to the family of α/β-hydrolases to host the Lipase Engineering database. Release 2.3 contains 6138 sequences and 167 experimentally determined protein structures, which are assigned to 37 superfamilies 103 homologous families.

Conclusion

DWARF has been designed for constructing databases of large structurally related protein families and for evaluating their sequence-structure-function relationships by a systematic analysis of sequence, structure and functional annotation. It has been applied to predict biochemical properties from sequence, and serves as a valuable tool for protein engineering.
methBLAST and methPrimerDB: web-tools for PCR based methylation analysis
Authors: Pattyn Filip , Hoebeeck Jasmien , Robbrecht Piet , Michels Evi , De Paepe Anne , Bottu Guy , Coornaert David , Herzog Robert , Speleman Frank , Vandesompele Jo
Published: November 2006

Background

DNA methylation plays an important role in development and tumorigenesis by epigenetic modification and silencing of critical genes. The development of PCR-based methylation assays on bisulphite modified DNA heralded a breakthrough in speed and sensitivity for gene methylation analysis. Despite this technological advancement, these approaches require a cumbersome gene by gene primer design and experimental validation. Bisulphite DNA modification results in sequence alterations (all unmethylated cytosines are converted into uracils) and a general sequence complexity reduction as cytosines become underrepresented. Consequently, standard BLAST sequence homology searches cannot be applied to search for specific methylation primers.

Results

To address this problem we developed methBLAST, a sequence similarity search program, based on the original BLAST algorithm but querying in silico bisulphite modified genome sequences to evaluate oligonucleotide sequence similarities. Apart from the primer specificity analysis tool, we have also developed a public database termed methPrimerDB for the storage and retrieval of validated PCR based methylation assays. The web interface allows free public access to perform methBLAST searches or database queries and to submit user based information. Database records can be searched by gene symbol, nucleotide sequence, analytical method used, Entrez Gene or methPrimerDB identifier, and submitter's name. Each record contains a link to Entrez Gene and PubMed to retrieve additional information on the gene, its genomic context and the article in which the methylation assay was described. To assure and maintain data integrity and accuracy, the database is linked to other reference databases. Currently, the database contains primer records for the most popular PCR-based methylation analysis methods to study human, mouse and rat epigenetic modifications. methPrimerDB and methBLAST are available at http://medgen.ugent.be/methprimerdb and http://medgen.ugent.be/methblast.

Conclusion

We have developed two integrated and freely available web-tools for PCR based methylation analysis. methBLAST allows in silico assessment of primer specificity in PCR based methylation assays that can be stored in the methPrimerDB database, which provides a search portal for validated methylation assays.
Rtt107/Esc4 binds silent chromatin and DNA repair proteins using different BRCT motifs
Authors: Zappulla David C , Maharaj Arindel SR , Connelly Jessica J , Jockusch Rebecca A , Sternglanz Rolf
Published: November 2006

Background

By screening a plasmid library for proteins that could cause silencing when targeted to the HMR locus in Saccharomyces cerevisiae, we previously reported the identification of Rtt107/Esc4 based on its ability to e stablish s ilent c hromatin. In this study we aimed to determine the mechanism of Rtt107/Esc4 targeted silencing and also learn more about its biological functions.

Results

Targeted silencing by Rtt107/Esc4 was dependent on the SIR genes, which encode obligatory structural and enzymatic components of yeast silent chromatin. Based on its sequence, Rtt107/Esc4 was predicted to contain six BRCT motifs. This motif, originally identified in the human breast tumor suppressor gene BRCA1, is a protein interaction domain. The targeted silencing activity of Rtt107/Esc4 resided within the C-terminal two BRCT motifs, and this region of the protein bound to Sir3 in two-hybrid tests. Deletion of RTT107/ESC4 caused sensitivity to the DNA damaging agent MMS as well as to hydroxyurea. A two-hybrid screen showed that the N-terminal BRCT motifs of Rtt107/Esc4 bound to Slx4, a protein previously shown to be involved in DNA repair and required for viability in a strain lacking the DNA helicase Sgs1. Like SLX genes, RTT107ESC4 interacted genetically with SGS1; esc4 Δ sgs1 Δ mutants were viable, but exhibited a slow-growth phenotype and also a synergistic DNA repair defect.

Conclusion

Rtt107/Esc4 binds to the silencing protein Sir3 and the DNA repair protein Slx4 via different BRCT motifs, thus providing a bridge linking silent chromatin to DNA repair enzymes.
Socio-economic status and types of childhood injury in Alberta: a population based study
Authors: Gilbride Susan J , Wild Cameron , Wilson Douglas R , Svenson Lawrence W , Spady Donald W
Published: November 2006

Background

Childhood injury is the leading cause of mortality, morbidity and permanent disability in children in the developed world. This research examines relationships between socio-economic status (SES), demographics, and types of childhood injury in the province of Alberta, Canada.

Methods

Secondary analysis was performed using administrative health care data provided by Alberta Health and Wellness on all children, aged 0 to 17 years, who had injuries treated by a physician, either in a physician's office, outpatient department, emergency room and/or as a hospital inpatient, between April 1st. 1995 to March 31st. 1996. Thirteen types of childhood injury were assessed with respect to age, gender and urban/rural location using ICD9 codes, and were related to SES as determined by an individual level SES indicator, the payment status of the Alberta provincial health insurance plan. The relationships between gender, SES, rural/urban status and injury type were determined using logistic regression.

Results

Twenty-four percent of Alberta children had an injury treated by physician during the one year period. Peak injury rates occurred about ages 2 and 13–17 years. All injury types except poisoning were more common in males. Injuries were more frequent in urban Alberta and in urban children with lower SES (receiving health care premium assistance). Among the four most common types of injury (78.6% of the total), superficial wounds and open wounds were more common among children with lower SES, while fractures and dislocations/sprains/strains were more common among children receiving no premium assistance.

Conclusion

These results show that childhood injury in Alberta is a major health concern especially among males, children living in urban centres, and those living on welfare or have Treaty status. Most types of injury were more frequent in children of lower SES. Analysis of the three types of the healthcare premium subsidy allowed a more comprehensive picture of childhood injury with children whose families are on welfare and those of Treaty status presenting more frequently for an injury-related physician's consultation than other children. This report also demonstrates that administrative health care data can be usefully employed to describe injury patterns in children.