bluuebunny/crossref_metadata_2025 huggingface dataset:
Rate of Head Circumference Growth as a Function of Autism Diagnosis and History of Autistic Regression
Authors: Webb Sara Jane , Nalty Theresa , Munson Jeff , Brock Catherine , Abbott Robert , Dawson Geraldine
Published: October 2007

Several reports indicate that autism spectrum disorder is associated with increased rate of head growth in early childhood. Increased rate of growth may index aberrant processes during early development, may precede the onset of symptoms, and may predict severity of the disease course. We examined rate of change in occipitofrontal circumference measurements (abstracted from medical records) in 28 boys with autism spectrum disorder and in 8 boys with developmental delay without autism from birth to age 36 months. Only children who had more than 3 occipitofrontal circumference measurements available during this age period were included. All data were converted to z scores based on the Centers for Disease Control and Prevention norms. Rate of growth from birth to age 36 months was statistically significantly higher for the autism spectrum disorder group than the developmental delay group, with children with autism spectrum disorder showing a statistically significant increase in occipitofrontal circumference relative to norms between 7 and 10 months; this group difference in rate of growth was more robust when height was used as a covariate. Rate of growth was not found to be different for children with autism spectrum disorder whose parents reported a history of loss of skills (regression) vs those whose parents reported early onset of autism symptoms. Findings from this study suggest that the aberrant growth is present in the first year of life and precedes the onset and diagnosis in children with autism spectrum disorder with and without a history of autistic regression.
Clinical and Genetic Study of Spinal Muscular Atrophies in Oman
Authors: Koul Roshan , Al Futaisi Amna , Chacko Alexander , Rao Vasudev , Simsek Mehmet , Muralitharan Shanmugakonar , Ganguly Shyam S. , Bayoumi Riad
Published: October 2007

This article presents a retrospective study and a prospective study on spinal muscular atrophy in Oman. For the retrospective study, data were collected from neurophysiology records, from both inpatient and outpatient files. The prospective study was conducted on children as they presented to the hospital and was funded by Sultan Qaboos University. The patients of spinal muscular atrophy were classified into types I, II, and III based on their clinical features as per the International Spinal Muscular Atrophy Consortium classification. The incidence of spinal muscular atrophy was about 1 per 6000 live births. Spinal muscular atrophy type I formed 65% of the cases. Survival motor neuron deletion was seen in 70% of cases of all types of spinal muscular atrophy. The deletion was 83% in spinal muscular atrophy type I. A further study to look into the nondeletional cases is in progress.
Iatrogenic Botulism in a Child With Spastic Quadriparesis
Authors: Partikian Arthur , Mitchell Wendy G.
Published: October 2007

Botulinum toxins are potent neurotoxins used in a variety of neurological disorders. Few pediatric reports have been published to date regarding the potential hazards of therapeutic use of botulinum toxins. We describe the case of a 10-year-old boy who developed systemic weakness following treatment of spasticity with botulinum toxin type B. The patient developed iatrogenic botulism with ptosis, facial diplegia, neck flexor and extensor weakness, and profound hypopharyngeal laxity with respiratory compromise from which he eventually recovered. Clinicians should be mindful of the risk for systemic botulism when using local injections of the neurotoxin.
Arterial Ischemic Stroke in Childhood: Risk Factors and Outcome in Old Versus New Era
Authors: Gökben Sarenur , Tosun Ayse , Bayram Nuri , Serdaroglu Gul , Polat Muzaffer , Kavakli Kaan , Tekgul Hasan
Published: October 2007

Risk factors of children with arterial ischemic stroke were retrospectively evaluated. The children were grouped according to values on developing diagnostic tools: 13 in the old era (1987-1994) and 18 in the new era (1995-2004). The old era battery included 5 tests: protein C, protein S, antithrombin, lupus anticoagulants, and anticardiolipin antibodies. The new era battery added 5 more tests: homocystine level, factor VIII level, mutations for factor V Leiden and prothrombin G20210A, and lipoprotein (a) level. At least 1 risk factor was found in 5 of 13 children (38.5%) in the old era and in 8 of 18 (44.4%) in the new era. The extended battery for prothrombotic disorders revealed 7 risk factors in 4 children (22.2%) in the new era, whereas the limited battery identified a single risk factor in 1 child (7.7%) in the old era. For the correct etiologic identification, prothrombotic risk factors should be extensively evaluated in patients with arterial ischemic stroke.
Identity Politics: The Struggle for Recognition or Hegemony?
Authors: Kaya Ibrahim
Published: October 2007

This article aims to answer the question whether identity-based movements are free from economic interests. By analyzing the actions and orientations of the Islamists in Turkey, I show that new social movements based on cultural identities are far from representing the demands of groups for recognition. Rather, these movements aim at establishing hegemony by controlling the intellectual life of society by cultural means. It is insisted that we need a Gramscian view of culture in order to understand the so-called identity politics. Identity-based movements do not refer to the end of social classes, but to the emergence of a new middle class. And against the advocating perspectives on identity politics, I argue that the possible solution to the question of fragmentation could be found in the idea of republic that does not prioritize any culture but seeks a central element that makes it meaningful to talk about such a collective arrangement as society.
The Albanian Renaissance in Political Thought: Between the Enlightenment and Romanticism
Authors: Ypi Lea L.
Published: October 2007

The conceptual genealogy of the Albanian so-called Renaissance is often linked to the influence of Western Romantic ideas on the nationalist movements of the Balkans. This paper analyzes the specificities of the Albanian cultural and political context and suggests, by contrast, that Enlightenment categories provide a better means of comprehension of this stage in Albanian intellectual history. It focuses on the ideological function played by the critique of religion as well as by a cultural project addressed to political struggle and emphasizes its roots in the Enlightenment tradition. It finally argues that Enlightenment concepts such as self-criticism and rational teleology might help to grasp some unique features of the Renaissance movement and to construct a more sophisticated account of the emergence of the Albanian modern state.
Mihai Şora: A Philosopher of Dialogue
Authors: Craiutu Aurelian
Published: October 2007

This article examines the political philosophy of Mihai Şora, one of the most important contemporary Romanian philosophers and the former minister of education in Romania's first post-communist government. After presenting Şora's unique intellectual trajectory that spans over six decades, the article explores in detail his theory of authenticity and alienation as well as his philosophy of dialogue and civil society. Şora's writings shed light on the tension between politics and philosophy and challenge us to rethink the relationship between freedom, authenticity, and liberal principles and values. The final section revisits the role of philosophers in the context of the fledgling Eastern European democratic regimes.
Discourses of Violence and the Ideological Strategies of the Romanian Communist Party, 1944-1953
Authors: Adamson Kevin
Published: October 2007

Empirical research linking violence and ideology—and using discourse theory and analysis—could provide more nuanced insights into political strategies and social contexts associated with the violent imposition of new political orders. This study addresses one such case, that of the communist takeover in Romania between 1944 and 1953, engaging in an analysis of Romanian Communist Party (PCR) discourse. Using concepts from discourse theory as a tool to critically re-examine some of the most influential comparative and Romania-specific scholarship on communist regimes, the article suggests that the PCR's rise to power was underpinned by a coherent ideological strategy. This involved the articulation of violence within a new discursive formation that sought to produce consent for the regime. In Romania's case, these findings call into question the coercion/consent dichotomy that has framed many previous analyses.
Populist Construction of the Past and Future: Emotional Campaigning in Hungary between 2002 and 2006
Authors: Rajacic Agnes
Published: October 2007

This article was finalized in April 2006, just after the last general elections in Hungary, and it explains the political developments until that date. It is well known that on 17 September an unprecedented revolt broke out in the country, with a direct confrontation of civilians and the police forces including the siege of the National television and the detention of hundreds of protestors. The explanation given for the revolt was the prime minister's leaked speech on the political lies of his own socialist party and the unrevealed economic situation of the country. Yet this article—written before the revolts—shows that confrontation was not solely the consequence of the leaked speech of the prime minister but of an already existing climate of political confrontation, here called “new populism.”
Teamwork Involving Qualitative Data Analysis Software
Authors: Sin Chih Hoong
Published: October 2007

Increasing sophistication of qualitative data analysis software facilitates its use on larger and more complex projects. Yet the way in which its use is operationalized in a team context is underexamined. This article explores the use of NUD*ist Version 6 (N6) in a large-scale evaluation. The way N6 was used in this evaluation was not merely determined by the functions it contains but by a series of pragmatic decisions resulting from the need to manage the complex logistics of a large, multisite team. Such dynamics affect the way in which data are understood and interrogated, thus inevitably influencing the nature of evidence created.
Television quiz show simulation
Authors: Hill Jonnie Lynn
Published: October 2007

This article explores the simulation of four television quiz shows for students in China studying English as a foreign language (EFL). It discusses the adaptation and implementation of television quiz shows and how the students reacted to them.
Coase and Van Zandt on Lighthouses
Authors: Barnett William , Block Walter
Published: October 2007

Mainstream economics maintains that ``public'' goods will not be provided (adequately) by free markets. Rather, if society is to have (efficient amounts of) public goods, government intervention is required. Traditionally, lighthouses, along with national defense, were held up as the quintessential examples of such public goods that require governmental intervention if they are to be provided (in optimal amounts). This changed, however, with Coase, who maintained and is widely credited with proving that, historically, the market (i.e., free enterprise) provided lighthouse services. Our thesis is that although Van Zandt showed Coase's claim to be mistaken on the basis of this valid criticism of Coase, Van Zandt erroneously concludes that private lighthouses were not historically operational. The truth of the matter, we aver, is that private lighthouses were indeed historically operational, and that although Van Zandt himself provides evidence for this claim, he fails to recognize it as such.
Do Tobacco-Control Programs Lower Tobacco Consumption?
Authors: Marlow Michael L.
Published: October 2007

California is often considered the model for tobacco-control programs due to its early adoption of comprehensive programs aimed at lowering tobacco consumption. Tobacco control began when voters approved the California Tobacco Tax and Health Promotion Act of 1988. More than $2 billion has been spent on tobacco-control in California since 1988. The findings of this article indicate that tobacco-control spending is a significant factor for the widening gap between consumption in the United States and in California only in equations that exclude cigarette prices and smoking bans as control variables. When significant, however, estimates suggest that, for every $1 increase in tobacco-control spending per capita, the sales gap widens by only 0.11 to 0.18 cigarette packs per capita, or roughly 2 to 4 cigarettes per capita. This study suggests that future research should address the complexity of interactions among tobacco-control programs, cigarette prices, and smoking bans.
Social Networks and the Creation of the Pitt Rivers Museum
Authors: Larson Frances , Petch Alison , Zeitlyn David
Published: October 2007

We consider how far different `networks of connection' have structured the relationships between curators, collectors and objects at the Pitt Rivers Museum at Oxford University. Museum collections are generated through complicated, fluctuating circulations of people and things that are literally endless and, when there is a high standard of computerized documentation, network analysis can be a stimulating and revealing methodological tool. Network analysis can reveal patterns in sets of social relationships that are too large to process or analyse mentally, and it can be a spur to more in-depth, nuanced research. An introduction to network theory and a consideration of `network' as a metaphor for social and material interactions more broadly is followed by a discussion of our research into the history of the Pitt Rivers Museum and an assessment of the strengths and weaknesses of network analysis as a research tool in the museum context.
Avtomat Kalashnikova
Authors: Graves-Brown Paul
Published: October 2007

This article examines the history of the ubiquitous Russian Avtomat Kalashnikova assault rifle (AK). Does it possess systemic characteristics that predispose its subversion from its intended purpose? The invention lineage of automatic weapons is considered in parallel with developments in the social organization of warfare. The AK is then evaluated in this context. In both technical and social terms, the use of the weapon by insurgents or in developing countries is not as remote from its intended function as would initially appear to be the case. Moreover, it is argued, the success of the AK is largely a result of the fact that it is a counter example to the prevailing episteme of technological progress.
Relational quality and media use in interpersonal relationships
Authors: Baym Nancy K. , Zhang Yan Bing , Kunkel Adrianne , Ledbetter Andrew , Lin Mei-Chen
Published: October 2007

This study examines the relationship between relational quality and media use in relationships. In addition, the impacts of other potentially important variables such as the sex and relationship type of the participants and their partners are explored. College student participants focused on interaction experiences with an acquaintance, friend, romantic partner or family member. The results indicated that participant sex and partner sex did not affect reported media use, whereas relationship type had significant effects on the extent to which face-to-face and telephone communication were used. Relationships with acquaintances had the lowest relational quality and romantic relationships, while closer, were less satisfying than either family or friendship relationships. Same-sex relationships were perceived as more satisfying than cross-sex relationships. Finally, media use did not predict relational closeness or satisfaction.
`Extending Society': the role of personal networks and gratification-utilities in the use of interactive communication media
Authors: Dimmick John , Ramirez Artemio , Wang Tao , Lin Shu-Fang
Published: October 2007

This study examined the relationship among personal network characteristics, gratification-utilities and the frequency of use of three interactive communication technologies (landline telephone, email and instant messaging). A conceptual framework is presented, providing a rationale for three hypotheses predicting positive relationships between personal network characteristics (size, intimacy and physical proximity), gratification-utilities and frequency of use.The participants were 286 college students, whom research shows are primary users of interactive media. Hypotheses 1 and 2, proposing a link between network characteristics and gratification-utilities with frequency of use, were supported, while Hypothesis 3, predicting a link between the prior two variables, was only partially supported. Frequency of use was associated more strongly with network characteristics than with gratification-utilities across the three technologies. Of the network characteristics, network size was significantly associated with gratification-utilities. Directions for future research are discussed.
The half-life of internet references cited in communication journals
Authors: Dimitrova Daniela V. , Bugeja Michael
Published: October 2007

This exploratory study examines the use of online citations, focusing on five leading journals in journalism and communication. It analyzes 1126 URL reference addresses in citations of articles published between 2000 and 2003. The results show that only 61 percent of the online citations remain accessible in 2004 and 39 percent do not. The content analysis also shows that .org and .gov are the most stable domains. Error messages for `dead' URL addresses are explored. The instability of online citations raises concerns for researchers, editors and associations.
Rethinking the fragmentation of the cyberpublic: from consensus to contestation
Authors: Dahlberg Lincoln
Published: October 2007

Recently there has been some debate between deliberative democrats about whether the internet is leading to the fragmentation of communication into `like-minded' groups.This article is concerned with what is held in common by both sides of the debate: a public sphere model that aims for all-inclusive, consensus seeking rational deliberation that eliminates inter-group `polarizing' politics. It argues that this understanding of deliberative democracy fails to adequately consider the asymmetries of power through which deliberation and consensus are achieved, the inter-subjective basis of meaning, the centrality of respect for difference in democracy, and the democratic role of `like-minded' deliberative groups.The deliberative public sphere must be rethought to account more fully for these four aspects. The article draws on post-Marxist discourse theory and reconceptualizes the public sphere as a space constituted through discursive contestation.Taking this radicalized norm, it considers what research is needed to understand the democratic implications of the formation of `like-minded' groups online.
Biological contaminants identified from laryngeal mask airways
Authors: Lu J.R.
Published: October 2007

Ten laryngeal mask airways (LMA), reused between 10 and 40 times, were collected from two UK NHS hospitals. All had been cleaned, autoclaved, inspected and repackaged using routine procedures recommended by the manufacturer, and were ready for reuse. These devices were collected, unpacked and subject to the biochemical analysis of erythrosine B staining on the outer surface areas of samples cut from the middle of the tube, the front middle and tip of the cuff. Parallel physical analysis using infrared (IR) spectroscopy was performed on sample cuts from the same areas as for the staining. Both surface infrared spectroscopy and biochemical assay revealed strong deposition of protein-related biological debris on almost all LMAs, with cuffs being contaminated more intensively than tubes. The results reveal that routine hospital LMA cleaning and sterilisation, coupled with visual inspection, are inadequate for identifying and removing protein related biological debris on reused LMAs. In light of the concern of possible cross-contamination, single-use LMAs should be encouraged.
Bugs down under: the Aussie experience! ICNA annual travel award 2002 to 2003
Authors: Hughes J.
Published: October 2007

The nurse consultant (NC) is still a relatively new role in the UK, and has yet to be evaluated. However, they are well established in countries such as Australia, particularly nurse consultants in infection control (NCIC). Core competencies have also helped define their roles (Macbeth, 1999; Winchcombe, 2000). So in 2003, following a successful application for the ICNA travel award, I was able to visit Australia to see how the role has developed so far.
ICNA regional workshops — using national evidence-based guidelines to reduce the risk of catheter-related urinary tract infections: report of post-workshop activities and outcomes
Authors: Pellowe C.M. , Pratt R.J.
Published: October 2007

ollowing the publication in 2001 of national evidence-based guidelines for preventing healthcare-associated infections, a series of one-day workshops were conducted throughout ICNA regions. These aimed to support key healthcare professionals to use the guidelines as a catalyst to develop local strategies to promote clinical effectiveness and reduce the incidence of catheter-associated urinary tract infections in acute care settings. Almost 600 practitioners attended these highly interactive workshops and positively evaluated this opportunity to have a structured day out to reflect on current infection prevention practice and to develop quality improvement plans.

A follow-up questionnaire to participants demonstrated that respondents engaged in a wide range of post-workshop activities, including policy review and development, audit, in-service education, and establishing various working groups to identify and plan for changes in local guidelines and in clinical practice. Most respondents reported achievements in the objectives of their quality improvement plan. The format of these workshops, set within the context of clinical governance, can be adapted to other key areas of infection prevention and control practice, and is recommended.
The architecture of infection control
Authors: Noble A.
Published: October 2007

This article presents issues raised by a recent study which looked at how design can reduce healthcare-associated infections. It discusses aspects of briefing and design and identifies the need for important changes in current practice.
Critical role for Rsk2 in T-lymphocyte activation
Authors: Lin Jian-Xin , Spolski Rosanne , Leonard Warren J.
Published: October 2007

During T-cell activation, a number of cytokine-activated signaling cascades, including the Jak-STAT, phosphoinositol 3-kinase (PI 3-kinase), and mitogen-activated protein kinase (MAPK) pathways, play important roles in modulating the expression of target genes and mediating a cellular response. We now report that interleukin 2 (IL-2) and IL-15, but not IL-7, rapidly activate the p90 ribosomal S6 kinases, Rsk1 and Rsk2, in human T lymphocytes. Surprisingly, mouse spleen T cells transduced with either the wild-type or a dominant-negative (DN) Rsk2-expressing retrovirus could not be recovered, in contrast to the normal survival of T cells transduced with retroviruses expressing wild-type or DN mutants of Rsk1 or Rsk3. Examination of Rsk2 knockout (KO) mice revealed normal T-cell development, but these T cells had delayed cell-cycle progression and lower production of IL-2 in response to anti-CD3 and anti-CD28 stimulation in vitro. Moreover, Rsk2 KO mice had defective homeostatic T-cell expansion following sublethal irradiation in vivo, which is known to involve T-cell receptor (TCR), IL-2, and/or IL-15 signals, each of which we demonstrate can rapidly and potently activate Rsk2 in mouse T cells. These results indicate an essential nonredundant role of Rsk2 in T-cell activation.
The opposite effects of IL-15 and IL-21 on CLL B cells correlate with differential activation of the JAK/STAT and ERK1/2 pathways
Authors: de Totero Daniela , Meazza Raffaella , Capaia Matteo , Fabbi Marina , Azzarone Bruno , Balleari Enrico , Gobbi Marco , Cutrona Giovanna , Ferrarini Manlio , Ferrini Silvano
Published: October 2007

The clonal expansion of chronic lymphocytic leukemia (CLL) cells requires the interaction with the microenvironment and is under the control of several cytokines. Here, we investigated the effect of IL-15 and IL-21, which are closely related to IL-2 and share the usage of the common γ chain and of its JAK3-associated pathway. We found remarkable differences in the signal transduction pathways activated by these cytokines, which determined different responses in CLL cells. IL-15 caused cell proliferation and prevented apoptosis induced by surface IgM cross-linking. These effects were more evident in cells stimulated via surface CD40, which exhibited increased cell expression of IL-15Rα chain and, in some of the cases, also of IL-2Rβ. IL-21 failed to induce CLL cell proliferation and instead promoted apoptosis. Following cell exposure to IL-15, phosphorylation of STAT5 was predominantly observed, whereas, following stimulation with IL-21, there was predominant STAT1 and STAT3 activation. Moreover, IL-15 but not IL-21 caused an increased phosphorylation of Shc and ERK1/2. Pharmacological inhibition of JAK3 or of MEK, which phosphorylates ERK1/2, efficiently blocked IL-15–induced CLL cell proliferation and the antiapoptotic effect of this cytokine. The knowledge of the signaling pathways regulating CLL cell survival and proliferation may provide new molecular targets for therapeutic intervention.
Effective erythropoiesis and HbF reactivation induced by kit ligand in β-thalassemia
Authors: Gabbianelli Marco , Morsilli Ornella , Massa Adriana , Pasquini Luca , Cianciulli Paolo , Testa Ugo , Peschle Cesare
Published: October 2007

In human β-thalassemia, the imbalance between α- and non–α-globin chains causes ineffective erythropoiesis, hemolysis, and anemia: this condition is effectively treated by an enhanced level of fetal hemoglobin (HbF). In spite of extensive studies on pharmacologic induction of HbF synthesis, clinical trials based on HbF reactivation in β-thalassemia produced inconsistent results. Here, we investigated the in vitro response of β-thalassemic erythroid progenitors to kit ligand (KL) in terms of HbF reactivation, stimulation of effective erythropoiesis, and inhibition of apoptosis. In unilineage erythroid cultures of 20 patients with intermedia or major β-thalassemia, addition of KL, alone or combined with dexamethasone (Dex), remarkably stimulated cell proliferation (3-4 logs more than control cultures), while decreasing the percentage of apoptotic and dyserythropoietic cells (<5%). More important, in both thalassemic groups, addition of KL or KL plus Dex induced a marked increase of γ-globin synthesis, thus reaching HbF levels 3-fold higher than in con-trol cultures (eg, from 27% to 75% or 81%, respectively, in β-thalassemia major). These studies indicate that in β-thalassemia, KL, alone or combined with Dex, induces an expansion of effective erythropoiesis and the reactivation of γ-globin genes up to fetal levels and may hence be considered as a potential therapeutic agent for this disease.
Granulocytes do not express but acquire monocyte-derived tissue factor in whole blood: evidence for a direct transfer
Authors: Egorina Elena M. , Sovershaev Mikhail A. , Olsen Jan O. , Østerud Bjarne
Published: October 2007

Unlike unanimous opinion on tissue factor (TF) expression in monocytes, the quest for TF presence in granulocytes has been going on for decades. To study the cell origin and track the blood-borne TF, we assessed TF activity and protein levels, knocked-down endogenous TF expression with small interfering RNA (siRNA), and overexpressed TF–yellow fluorescent protein (TF-YFP) fusion in immunologically isolated human monocytes and granulocytes. Monocytes and, to a much lesser extent, granulocytes isolated from lipopolysaccharide (LPS)/phorbol 12-myristate-13-acetate (PMA)–stimulated whole blood contained active TF antigen. However, only monocytes possessed significant TF activity and protein levels when stimulated with LPS/PMA in suspension. Reintroduction of TF-silenced monocytes to whole blood led to a profound reduction of LPS/PMA-stimulated TF activity in both mononuclear cell (MNC) and granulocyte fractions. No reduction in TF activity in MNC and granulocyte fractions was observed when TF-silenced granulocytes were reintroduced to whole blood. As shown by immunoblotting, flow cytometry, and confocal microscopy, granulocytes became positive for TF-YFP when isolated from whole blood reconstituted with TF-YFP–expressing monocytes. Together, we pinpoint monocytes as a major source of TF and provide solid experimental evidence for a direct transfer of TF protein from the monocytes to granulocytes in the blood.
Effect of transfusional iron intake on response to chelation therapy in β-thalassemia major
Authors: Cohen Alan R. , Glimm Ekkehard , Porter John B.
Published: October 2007

The success of chelation therapy in controlling iron overload in patients with thalassemia major is highly variable and may partly depend on the rate of transfusional iron loading. Using data from the 1-year phase III study of deferasirox, including volumes of transfused red blood cells and changes in liver iron concentration (LIC) in 541 patients, the effect of iron loading on achieving neutral or negative iron balance was assessed in patients receiving different doses of deferasirox and the comparator deferoxamine. After dose adjustment, reductions in LIC after 1 year of deferasirox or deferoxamine therapy correlated with transfusional iron intake. At a deferasirox dose of 20 mg/kg per day, neutral or negative iron balance was achieved in 46% and 75% of patients with the highest and lowest transfusional iron intake, respectively; 30 mg/kg per day produced successful control of iron stores in 96% of patients with a low rate of transfusional iron intake. Splenectomized patients had lower transfusional iron intake and greater reductions in iron stores than patients with intact spleens. Transfusional iron intake should be monitored on an ongoing basis in thalassemia major patients, and the rate of transfusional iron loading should be considered when choosing the appropriate dose of an iron-chelating agent. This study is registered at http://clinicaltrials.gov as NCT00061750.
Topology independent protein structural alignment
Authors: Dundas Joe , Binkowski TA , DasGupta Bhaskar , Liang Jie
Published: October 2007

Background

Identifying structurally similar proteins with different chain topologies can aid studies in homology modeling, protein folding, protein design, and protein evolution. These include circular permuted protein structures, and the more general cases of non-cyclic permutations between similar structures, which are related by non-topological rearrangement beyond circular permutation. We present a method based on an approximation algorithm that finds sequence-order independent structural alignments that are close to optimal. We formulate the structural alignment problem as a special case of the maximum-weight independent set problem, and solve this computationally intensive problem approximately by iteratively solving relaxations of a corresponding integer programming problem. The resulting structural alignment is sequence order independent. Our method is also insensitive to insertions, deletions, and gaps.

Results

Using a novel similarity score and a statistical model for significance p-value, we are able to discover previously unknown circular permuted proteins between nucleoplasmin-core protein and auxin binding protein, between aspartate rasemase and 3-dehydrogenate dehydralase, as well as between migration inhibition factor and arginine repressor which involves an additional strand-swapping. We also report the finding of non-cyclic permuted protein structures existing in nature between AML1/core binding factor and ribofalvin synthase. Our method can be used for large scale alignment of protein structures regardless of the topology.

Conclusion

The approximation algorithm introduced in this work can find good solutions for the problem of protein structure alignment. Furthermore, this algorithm can detect topological differences between two spatially similar protein structures. The alignment between MIF and the arginine repressor demonstrates our algorithm's ability to detect structural similarities even when spatial rearrangement of structural units has occurred. The effectiveness of our method is also demonstrated by the discovery of previously unknown circular permutations. In addition, we report in this study the finding of a naturally occurring non-cyclic permuted protein between AML1/Core Binding Factor chain F and riboflavin synthase chain A.
MindSeer: a portable and extensible tool for visualization of structural and functional neuroimaging data
Authors: Moore Eider B , Poliakov Andrew V , Lincoln Peter , Brinkley James F
Published: October 2007

Background

Three-dimensional (3-D) visualization of multimodality neuroimaging data provides a powerful technique for viewing the relationship between structure and function. A number of applications are available that include some aspect of 3-D visualization, including both free and commercial products. These applications range from highly specific programs for a single modality, to general purpose toolkits that include many image processing functions in addition to visualization. However, few if any of these combine both stand-alone and remote multi-modality visualization in an open source, portable and extensible tool that is easy to install and use, yet can be included as a component of a larger information system.

Results

We have developed a new open source multimodality 3-D visualization application, called MindSeer, that has these features: integrated and interactive 3-D volume and surface visualization, Java and Java3D for true cross-platform portability, one-click installation and startup, integrated data management to help organize large studies, extensibility through plugins, transparent remote visualization, and the ability to be integrated into larger information management systems. We describe the design and implementation of the system, as well as several case studies that demonstrate its utility. These case studies are available as tutorials or demos on the associated website: http://sig.biostr.washington.edu/projects/MindSeer.

Conclusion

MindSeer provides a powerful visualization tool for multimodality neuroimaging data. Its architecture and unique features also allow it to be extended into other visualization domains within biomedicine.
Analysis on multi-domain cooperation for predicting protein-protein interactions
Authors: Wang Rui-Sheng , Wang Yong , Wu Ling-Yun , Zhang Xiang-Sun , Chen Luonan
Published: October 2007

Background

Domains are the basic functional units of proteins. It is believed that protein-protein interactions are realized through domain interactions. Revealing multi-domain cooperation can provide deep insights into the essential mechanism of protein-protein interactions at the domain level and be further exploited to improve the accuracy of protein interaction prediction.

Results

In this paper, we aim to identify cooperative domains for protein interactions by extending two-domain interactions to multi-domain interactions. Based on the high-throughput experimental data from multiple organisms with different reliabilities, the interactions of domains were inferred by a Linear Programming algorithm with Multi-domain pairs (LPM) and an Association Probabilistic Method with Multi-domain pairs (APMM). Experimental results demonstrate that our approach not only can find cooperative domains effectively but also has a higher accuracy for predicting protein interaction than the existing methods. Cooperative domains, including strongly cooperative domains and superdomains, were detected from major interaction databases MIPS and DIP, and many of them were verified by physical interactions from the crystal structures of protein complexes in PDB which provide intuitive evidences for such cooperation. Comparison experiments in terms of protein/domain interaction prediction justified the benefit of considering multi-domain cooperation.

Conclusion

From the computational viewpoint, this paper gives a general framework to predict protein interactions in a more accurate manner by considering the information of both multi-domains and multiple organisms, which can also be applied to identify cooperative domains, to reconstruct large complexes and further to annotate functions of domains. Supplementary information and software are provided in http://intelligent.eic.osaka-sandai.ac.jp/chenen/MDCinfer.htm and http://zhangroup.aporc.org/bioinfo/MDCinfer.
Improved human disease candidate gene prioritization using mouse phenotype
Authors: Chen Jing , Xu Huan , Aronow Bruce J , Jegga Anil G
Published: October 2007

Background

The majority of common diseases are multi-factorial and modified by genetically and mechanistically complex polygenic interactions and environmental factors. High-throughput genome-wide studies like linkage analysis and gene expression profiling, tend to be most useful for classification and characterization but do not provide sufficient information to identify or prioritize specific disease causal genes.

Results

Extending on an earlier hypothesis that the majority of genes that impact or cause disease share membership in any of several functional relationships we, for the first time, show the utility of mouse phenotype data in human disease gene prioritization. We study the effect of different data integration methods, and based on the validation studies, we show that our approach, ToppGene http://toppgene.cchmc.org, outperforms two of the existing candidate gene prioritization methods, SUSPECTS and ENDEAVOUR.

Conclusion

The incorporation of phenotype information for mouse orthologs of human genes greatly improves the human disease candidate gene analysis and prioritization.
Sequences conserved by selection across mouse and human malaria species
Authors: Imamura Hideo , Persampieri Jason H , Chuang Jeffrey H
Published: October 2007

Background

Little is known, either experimentally or computationally, about the genomic sequence features that regulate malaria genes. A sequence conservation analysis of the malaria species P. falciparum, P. berghei, P. yoelii, and P. chabaudi could significantly advance knowledge of malaria gene regulation.

Results

We computationally identify intergenic sequences conserved beyond neutral expectations, using a conservation algorithm that accounts for the strong compositional biases in malaria genomes. We first quantify the composition-specific divergence at silent positions in coding sequence. Using this as a background, we examine gene 5' regions, identifying 610 blocks conserved far beyond neutral expectations across the three mouse malariae, and 81 blocks conserved as strongly across all four species (p < 10-6). Detailed analysis of these blocks indicates that only a minor fraction are likely to be previously unknown coding sequences. Analogous noncoding conserved blocks have been shown to regulate adjacent genes in other phylogenies, making the predicted blocks excellent candidates for novel regulatory functions. We also find three potential transcription factor binding motifs which exhibit strong conservation and overrepresentation among the rodent malariae.

Conclusion

A broader finding of our analysis is that less malaria intergenic sequence has been conserved by selection than in yeast or vertebrate genomes. This supports the hypothesis that transcriptional regulation is simpler in malaria than other eukaryotic species. We have built a public database containing all sequence alignments and functional predictions, and we expect this to be a valuable resource to the malaria research community.
Experimental optimization of probe length to increase the sequence specificity of high-density oligonucleotide microarrays
Authors: Suzuki Shingo , Ono Naoaki , Furusawa Chikara , Kashiwagi Akiko , Yomo Tetsuya
Published: October 2007

Background

High-density oligonucleotide arrays are widely used for analysis of genome-wide expression and genetic variation. Affymetrix GeneChips – common high-density oligonucleotide arrays – contain perfect match (PM) and mismatch (MM) probes generated by changing a single nucleotide of the PMs, to estimate cross-hybridization. However, a fraction of MM probes exhibit larger signal intensities than PMs, when the difference in the amount of target specific hybridization between PM and MM probes is smaller than the variance in the amount of cross-hybridization. Thus, pairs of PM and MM probes with greater specificity for single nucleotide mismatches are desirable for accurate analysis.

Results

To investigate the specificity for single nucleotide mismatches, we designed a custom array with probes of different length (14- to 25-mer) tethered to the surface of the array and all possible single nucleotide mismatches, and hybridized artificially synthesized 25-mer oligodeoxyribonucleotides as targets in bulk solution to avoid the effects of cross-hybridization. The results indicated the finite availability of target molecules as the probe length increases. Due to this effect, the sequence specificity of the longer probes decreases, and this was also confirmed even under the usual background conditions for transcriptome analysis.

Conclusion

Our study suggests that the optimal probe length for specificity is 19–21-mer. This conclusion will assist in improvement of microarray design for both transcriptome analysis and mutation screening.
ADAM15 gene structure and differential alternative exon use in human tissues
Authors: Kleino Iivari , Ortiz Rebekka M , Huovila Ari-Pekka J
Published: October 2007

Background

ADAM15 is a metalloprotease-disintegrin implicated in ectodomain shedding and cell adhesion. Aberrant ADAM15 expression has been associated with human cancer and other disorders. We have previously shown that the alternative splicing of ADAM15 transcripts is mis-regulated in cancer cells. To gain a better understanding of ADAM15 regulation, its genomic organization and regulatory elements as well as the alternative exon use in human tissues were characterized.

Results

Human ADAM15, flanked by the FLJ32785/DCST1 and ephrin-A4 genes, spans 11.4 kb from the translation initiation codon to the polyadenylation signal, being the shortest multiple-exon ADAM gene. The gene contains 23 exons varying from 63 to 316 bp and 22 introns from 79 to 1283 bp. The gene appeared to have several transcription start sites and their location suggested the promoter location within a CpG island proximal to the translation start. Reporter expression experiments confirmed the location of functional GC-rich, TATAless and CAATless promoter, with the most critical transcription-supporting elements located -266 to -23 bp relative to the translation start. Normal human tissues showed different complex patterns of at least 13 different ADAM15 splice variants arising from the alternative use of the cytosolic-encoding exons 19, 20a/b, and 21a/b. The deduced ADAM15 protein isoforms have different combinations of cytosolic regulatory protein interaction motifs.

Conclusion

Characterization of human ADAM15 gene and identification of elements involved in the regulation of transcription and alternative splicing provide important clues for elucidation of physiological and pathological roles of ADAM15. The present results also show that the alternative exon use is a physiological post-transcriptional mechanism regulating ADAM15 expression in human tissues.
Prehospital score for acute disease: a community-based observational study in Japan
Authors: Toyoda Yasuhiro , Matsuo Yoshio , Tanaka Hiroyuki , Fujiwara Hidekazu , Takatorige Toshio , Iso Hiroyasu
Published: October 2007

Background

Ambulance usage in Japan has increased consistently because it is free under the national health insurance system. The introduction of refusal for ambulance transfer is being debated nationally. The purpose of the present study was to investigate the relationship between prehospital data and hospitalization outcome for acute disease patients, and to develop a simple prehospital evaluation tool using prehospital data for Japan's emergency medical service system.

Methods

The subjects were 9,160 consecutive acute disease patients aged ≥ 15 years who were transferred to hospital by Kishiwada City Fire Department ambulance between July 2004 and March 2006. The relationship between prehospital data (age, systolic blood pressure, pulse rate, respiration rate, level of consciousness, SpO2 level and ability to walk) and outcome (hospitalization or non-hospitalization) was analyzed using logistic regression models. The prehospital score component of each item of prehospital data was determined by beta coefficients. Eligible patients were scored retrospectively and the distribution of outcome was examined. For patients transported to the two main hospitals, outcome after hospitalization was also confirmed.

Results

A total of 8,330 (91%) patients were retrospectively evaluated using a prehospital score with a maximum value of 14. The percentage of patients requiring hospitalization rose from 9% with score = 0 to 100% with score = 14. With a cut-off point score ≥ 2, the sensitivity, specificity, positive predictive value and negative predictive value were 97%, 16%, 39% and 89%, respectively. Among the 6,498 patients transported to the two main hospitals, there were no deaths at scores ≤ 1 and the proportion of non-hospitalization was over 90%. The proportion of deaths increased rapidly at scores ≥ 11.

Conclusion

The prehospital score could be a useful tool for deciding the refusal of ambulance transfer in Japan's emergency medical service system.