bluuebunny/crossref_metadata_2025 huggingface dataset:
Prediction uncertainties and inaccuracies resulting from common assumptions in modelling vibration from underground railways
Authors: Jones Simon , Kuo Kirsty , Hussein Mohammed , Hunt Hugh
Published: March 2012

Underground railways produce significant ground-borne vibration that is reported to disturb people living or working near subways. Designers and engineers use numerical models to predict vibration levels so as to meet the increasingly strict vibration standards. These models commonly include simplifying assumptions to reduce the complexity and cost of the simulation. This paper reviews six commonly disregarded aspects of the underground railway environment and their respective effects on vibration prediction values: a second (twin) tunnel, piled foundations, track with discontinuous slabs, soil inhomogeneity, inclined soil layers, and irregular contact at the tunnel–soil interface. Results suggest that accounting for each of these simplifying assumptions can result in predictions that vary from the simplified cases by at least 5 dB and potentially up to 20 dB. This is a significant level of uncertainty and should be considered when estimating the predictive accuracy of numerical models using simplifying assumptions.
Railway axle failures and durability validation
Authors: Grubisic Vatroslav , Fischer Gerhard
Published: March 2012

In this paper the influence of the approach taken to the design of train axles is considered and the shortcomings of the currently used procedures for fatigue strength validation are discussed. The procedure proposed in existing standards assumes a fatigue endurance limit, that is not realistically applicable to actual service conditions, and they do not take into account the real stresses encountered in actual service. The problems generated by such an approach are discussed using examples of actual failures of passenger train axles in Germany. A practice-related procedure for the service strength validation is proposed. This procedure includes service-related stress spectra and the fatigue strength of axles. To validate an axle design the time-varying stresses in individual critical areas of the axle, represented by their stress spectra, must be taken into account. The allowable stress levels in individual axle areas depend both on the fatigue strength and on the spectrum of operational stresses.
Overcoming Past Wrongs Committed by States
Authors: Suzuki Shogo
Published: March 2012

This article investigates whether or not reconciliation for historical wrongs can be realized in the absence of a state apology. States have traditionally been notoriously reluctant to apologize for their past crimes, and this has often meant that victims are unable to attain closure while they are still alive. What, then, are the alternatives? This article examines the case of the Women’s International War Crimes Tribunal on Japan’s Military Sexual Slavery, which was held in 2000. The Tribunal was organized primarily by non-governmental organizations: its judgements were neither legally binding, nor was the Tribunal capable of issuing a ‘sincere’ apology that was the equivalent of a state apology. Nevertheless, this article makes the case that faced with the fact that the Japanese state has not always been forthcoming in acknowledging and taking legal responsibility for its past wrongs, such private, non-state attempts may constitute the best chance for us to accord some victims of war crimes some sense of closure for their past suffering.
Pattern-based formulation: a methodology for psychiatric case formulation
Authors: Fernando Irosh , Cohen Martin , Henskens Frans
Published: March 2012

Objective: Psychiatric formulation is often considered a challenging task, particularly for trainees and students in psychiatry. The process of arriving at a good psychiatric formulation involves identifying major issues of the patient, and developing an explanatory system, which can be derived using known theoretical models in psychiatry. A good explanatory system should provide a high degree of coherence by linking the most relevant data, justification for the proposed management plan, and its feasibility. Unfortunately, the literature on ‘how’ to develop psychiatric formulation is limited, and for the trainees, psychiatric formulation remains a challenging task.

Method: Based on the clinical reasoning strategy known as pattern recognition, a methodology for psychiatric case formulation has been proposed. The methodology uses a repository of templates, which are derived from major theoretical models in psychiatry. Developing a formulation involves a process of selecting, prioritising and combining templates according to the elicited set of main issues or psychopathology. The pattern resulting from the combination of different templates provides a degree of uniqueness to the explanatory system.

Conclusion: It is expected that this methodology will help trainees and students to develop a broader understanding and skills in psychiatric formulation.
The myth of Jocasta and maternal narcissism
Authors: Butterfield Ingrid
Published: March 2012

Objective: This paper utilises the ancient Greek myth of Oedipus, and in particular the character’s frequently overlooked mother Jocasta, to highlight some of the issues associated with maternal narcissism.

Conclusions: A discussion of Jocasta forms the background to case studies where a mother’s narcissism, along with an absent father, was pivotal to coping difficulties, which ultimately compelled the patient to seek therapy. Consideration of the Oedipus–Jocasta interpersonal dynamic can contribute to a greater understanding of these patients.
Multilocular Cystic Renal Cell Carcinoma in Lower Pole Moiety of a Duplex Kidney
Authors: Liu Guang-Ming , Ma Hong-Shun , Li Yan-Min
Published: March 2012

Multilocular cystic renal cell carcinoma (MCRCC) is an uncommon low-grade renal cell carcinoma with unique morphologic features. The 2004 World Health Organization classification of kidney tumors categorized MCRCC as a separate entity. The authors report the case of a 48-year-old man whose MCRCC originated from the lower portion of the duplex kidney (DK). Because the oncological outcome of MCRCC is favorable, regardless of tumor size and stage, patients with MCRCC might benefit from nephron-sparing surgery. It is important to distinguish larger MCRCCs from other renal cell carcinomas, especially when comorbid with DK, because the characteristic anatomy of DK warrants the nephron-sparing surgery. To the authors’ knowledge, MCRCC in DK has not been reported previously in the English literature.
Do Adventitial Mast Cells Contribute to the Pathogenesis of Ascending Thoracic Aorta Aneurysm?
Authors: Anvari Maryam Sotoudeh , Boroumand Mohammad Ali , Mojarad Elham Ameli , Karimi Abbasali , Abbasi Kyomars , Shirzad Mahmood , Omran Abbas Salehi , Movahedi Namvar , Shirani Shapour , Goodarzynejad Hamidreza
Published: March 2012

The precise pathogenesis of the ascending aortic aneurysm (AscAA) remains to be determined. Mast cells in the adventitia of human AscAA lesions may play a role in this pathogenesis. Adventitial mast cell density per 10 high-power fields (0.25 mm2) was assessed in multiple biopsy samples, from aneurysmal aortic sections (n = 41) and control (nondilated) aortic specimens (n = 50), stained by orcein-Giemsa method, an inexpensive (<$1) method. In a multivariable adjusted logistic regression model, using AscAA as the dependent variable, mast cell density was found to be an independent predictor of AscAA occurrence (odds ratio = 2.21; 95% confidence interval = 1.58-3.08; P < .001). Receiver operating characteristic curve analysis showed that the proposed cutoff value of ≥3 mast cells per 10 high-power fields was very sensitive to detect AscAA occurrence, yielding a sensitivity of 90% with a specificity of 80%. In conclusion, a significant increase in the number of mast cells in the adventitia of human ascending aortic lesions proposes a role for these cells in the pathogenesis of AscAA.
Behavioral Counseling for Cardiovascular Disease Prevention in Primary Care Settings
Authors: Bock Christina , Diehl Katharina , Schneider Sven , Diehm Curt , Litaker David
Published: March 2012

Cardiovascular disease carries a substantial public health burden. Physician advice on modifying behavioral risk factors is effective, yet the practice of and factors associated with behavioral counseling in primary care have not been systematically investigated. The authors conducted a systematic review that identified 18 studies providing data on 6,338 physicians. The provision of preventive services differed by patients’ individual risk. Physicians’ counseling on smoking cessation was most commonly reported. The proportions of physicians counseling about nutrition and physical activity were notably lower and few physicians took further action by using more intensive counseling approaches. As studies were mainly based on self-reports, current delivery of preventive services may be overestimated. There is a need to increase the frequency of behavioral counseling in primary care settings, particularly for nutrition and physical activity, and to emphasize that counseling may also benefit individuals without cardiovascular disease risk factors.
Crossing the sea from They to We? The unfolding of knowing and practising in collaborative research
Authors: Marcos Javier , Denyer David
Published: March 2012

This article addresses how knowing and practising unfolds in collaborative research amongst practitioners from a large consulting and business services group and academics from a UK School of Management. Dialogue enabled actors to cross between theory and practice by providing a ‘space’ for support, challenge, exchange and experimentation. However, this ‘space’ was fragile and the insensitive actions of one individual, driven by institutional pressure to exploit the project for competitive advantage, resulted in withdrawal and the re-establishment of traditional divisions. Our view is that collaborative research is not necessarily an exercise in producing, transferring and implementing research findings but is better thought of as knowledge integration through a dialogue of theory and practice. The article contributes to the ongoing debate about the relevance of management research and the theoretical development of knowledge co-production.
A genome-wide association study in progressive multiple sclerosis
Authors: Martinelli-Boneschi Filippo , Esposito Federica , Brambilla Paola , Lindström Eva , Lavorgna Giovanni , Stankovich Jim , Rodegher Mariaemma , Capra Ruggero , Ghezzi Angelo , Coniglio Gabriella , Colombo Bruno , Sorosina Melissa , Martinelli Vittorio , Booth David , Oturai Annette Bang , Stewart Graeme , Harbo Hanne F. , Kilpatrick Trevor John , Hillert Jan , Rubio Justin P , Abderrahim Hadi , Wojcik Jerome , Comi Giancarlo
Published: March 2012

Background: The role played by genetic factors in influencing the clinical course of multiple sclerosis (MS) is not yet well established.

Objective: We aimed to identify genetic variants associated with progressive MS (PrMS).

Methods: We conducted a genome-wide association study (GWAS) in 197 patients with PrMS and 234 controls of Italian origin. We tested the top 20 single nucleotide polymorphisms (SNPs) with suggestive evidence of association ( p-value<10−4) in two independent sets of primary progressive MS cases and controls.

Results: We identified a risk-associated SNP in the HLA region in linkage disequilibrium (LD) with DRB1*1501 and DQB*0602 loci, with genome-wide significance (rs3129934T, pcombined=6.7×10-16, OR=2.34, 95% CI=1.90–2.87), and a novel locus on chromosome 7q35 with suggestive evidence of association (rs996343G, pcombined=2.4×10-5, OR=0.70, 95% CI=0.59–0.83) which maps within a human endogenous retroviral (HERV) element. The new locus did not have a ‘ cis’ effect on RNA expression in lymphoblastic cell lines, but pathway analyses of ‘ trans’ effects point to an expression regulation of genes involved in neurodegeneration, including glutamate metabolism ( p<0.01) and axonal guidance signalling ( p<0.02).

Conclusions: We have confirmed the established association with the HLA region and, despite the low statistical power of the study, we found suggestive evidence for association with a novel locus on chromosome 7, with a putative regulatory role.
A pilot study of the immunological effects of high-dose vitamin D in healthy volunteers
Authors: Allen Aideen C , Kelly Siobhan , Basdeo Sharee A , Kinsella Katie , Mulready Keith J , Mills Kingston HG , Tubridy Niall , Walsh Cathal , Brady Jennifer J , Hutchinson Michael , Fletcher Jean M
Published: March 2012

Although vitamin D deficiency is considered an environmental factor in multiple sclerosis (MS), the immunological and clinical effects of vitamin D supplementation remain unclear. We performed a pilot study of the immunomodulatory effects of vitamin D in healthy individuals ( n=4), who took 5000–10,000 IU/day of vitamin D over 15 weeks. After 15 weeks of vitamin D supplementation, serum 25(OH) vitamin D levels rose significantly from baseline, with a corresponding increase in IL-10 production by peripheral blood mononuclear cells and a reduced frequency of Th17 cells. These data provide a strong rationale for randomised trials to assess the clinical effects of vitamin D supplementation in MS.
Language shift and host society attitudes: Dutch migrants who arrived in New Zealand between 1950 and 1965
Authors: Crezee Ineke
Published: March 2012

A study published in 2010 reported on past and current language use of a group of older Dutch migrants in New Zealand. Dutch migrants were chosen because the researcher was herself a bilingual Dutch–English-speaking migrant and hence in a good position to understand respondents’ background and assess their language use in both English and Dutch. Respondents interviewed for the study consisted of 30 retired Dutch migrants, all of whom had arrived in New Zealand between 1950 and 1965 when they were aged between 18 and 35 years. All respondents were living in the Greater Auckland area and were aged between 65 and 92 years at the time of the interview. All respondents were asked questions based on a sociolinguistic life questionnaire and asked about their language use and experiences since migration. Interviews were recorded, and information from interviews and questionnaires was supplemented by data collected from participants’ adult children. This article will focus on respondents’ comments in relation to their motivation to either maintain their first language (L1) Dutch or shift to their second language (L2) English in the home environment. It appears that external societal attitudes affected respondents’ language use in a number of domains.
White ghettos: The ‘crisis of multiculturalism’ in post-unification Germany
Authors: Stehle Maria
Published: March 2012

This article traces the shifts in German discourses about multiculturalism and the failed experiment of multiculturalism from the early 1990s into the 21st century by analyzing anxieties about emerging ‘ethnic ghettos’ and ‘parallel societies’ in Europe. In these discourses, ‘Europe’ functions simultaneously as an example for the failures of multiculturalism and as a bastion of western values in need of protection. The second part of this article shifts to a discussion on creative political interventions that expose these tensions and contradictions and emphasize the historic dimension of racialized exclusion in Germany and the European context. They describe the effects of social exclusion and propose (often syncretic) translocal forms of solidarity and activism. In their irreverent, playful and performative interventions, activists and artists develop strategies to counter the essentialist culturalisms that underpin the debates about European integration, multiculturalism and the crisis of multiculturalism in the German context.
Who fears to speak in the new Europe? Plurilingualism and alterity
Authors: Cronin Michael
Published: March 2012

Language difference has become a public focus of debates around the alleged failure of European policies on multiculturalism. Integration into the dominant host language of the community is seen as the only desirable outcome for national language policies. This article argues for a wholly different approach to language alterity, drawing on understandings provided by translation, the relationship between time and place and a social ontology of conflict where language features as an important actor. Underlining the necessity of the ontological dimension of conflict for the emergence of identity in the case of language, plurality involves accepting that there is no final, definitive reconciliation of opposites but that any arrangement is a provisional, unstable equilibrium which does not rule out further conflict in the future. This understanding of language conflict provides a way of thinking about contemporary multilingual and multicultural societies in a manner that moves beyond revealed universalism and schismatic relativism.
Turbans, hijabs and other differences: ‘Integration from below’ and Irish interculturalism
Authors: Lentin Ronit
Published: March 2012

This article outlines the ease with which the Republic of Ireland had moved from publicly articulating Irish racism during the 1997 European Year Against Racism, to employing euphemisms such as interculturalism, transculturalism, integration and cultural diversity. In the rush to diversity, these euphemisms, employed unproblematically during the Irish economic boom, erase political terms such as ‘race’ and racism that state actors do not want to hear mentioned. Using examples of the racialization of specific populations, this article argues that the economic downturn led to the disappearance of integrationist discourses, as ‘race’, racism and immigration become but vague memories. Against the background of shadowy figures of turbaned and veiled migrants as the racialized trope of Irish ‘racism without racism’, the article argues that through the strategy of convening migrant-led associations and networks, migrants, though forced to appropriate state parlance, enact their own ‘integration from below’, making integration work in new exciting ways.
New hierarchies of belonging
Authors: Back Les , Sinha Shamser , Bryan with Charlynne
Published: March 2012

The article discusses the effects that the debate about the ‘crisis of multiculturalism’ is having on the regulation, scrutiny and the surveillance of migrant communities. Through the story of a young migrant it explores the ways that old hierarchies of belonging are taking new forms within the social landscape of contemporary London. This biographical case study is drawn from a larger qualitative study of 30 young adult migrants. Although the article focuses on a single case, its arguments are informed by the larger sample. The article argues that the debate about population mobility needs to transcend the ‘migrancy problematic’ and identify how the ordering of humanity works in a globalized and neo-liberal context. Combining insights from Stuart Hall’s recent writings and Franz Fanon’s lesser-known essays, the article argues that new hierarchies of belonging are established that replay aspects of colonial racism but in a form suited to London’s postcolonial situation.
Research, Practice, and the Space Between
Authors: Rogers Dallas
Published: March 2012

This article challenges the neoliberal discourse of “instrumental rationality” that is encroaching on theories of qualitative research, critical reflection, and subjectivity. I return to Foucault’s historical ontology of the self and the ancient Athenian precept care of the self to show that critical reflection and rationality have never been mutually exclusive. I put the care of the self metaphor to empirical use by examining the practical and ethical issues that emerged when I transitioned from a state-sponsored frontline employee working with public housing tenants, to a university researcher investigating public housing tenant participation in a state-sponsored urban redevelopment project. The focus is on my experiences as a practitioner-researcher working within two neoliberalized institutions, while also constructing a performative research ethic to mount a challenge against the politics of neoliberal “evidence” in the space between.
Amount of Exercise in the First Week After Stroke Predicts Walking Speed and Unassisted Walking
Authors: Scrivener Katharine , Sherrington Catherine , Schurr Karl
Published: March 2012

Background. Predicting walking outcomes poststroke is a challenge for clinicians. Objective. To identify the extent to which exercise dose (repetitions of leg movements) in the first week of a comprehensive stroke unit stay predicts discharge mobility. Methods. A cohort study was conducted on 200 consecutive people admitted to a comprehensive stroke unit who required physical therapy. Results. Discharge and predictor data were available for 191 survivors (99%). On admission, 86 participants were able to walk, and the average walking velocity was 0.42 m/s. On discharge, the average walking velocity was 0.77 m/s, and 152 participants were able to walk. A discharge walking velocity of greater than 0.8 m/s was predicted by the exercise dose achieved in the first week after admission. Adding other predictors did not significantly increase the predictive ability of the model. Completion of more than the median number of exercise repetitions (703) in the first week of admission was associated with a quicker recovery of unassisted walking. This effect persisted after adjustment for walking velocity on admission, cognition, and comorbidity. Conclusion. Exercise dose in the first week after admission for stroke is an important indicator of walking speed at discharge and the time to achieve unassisted walking.
Referral to Rehabilitation After Severe Traumatic Brain Injury
Authors: Jourdan Claire , Bayen Eleonore , Bosserelle Vanessa , Azerad Sylvie , Genet François , Fermanian Christophe , Aegerter Philippe , Pradat-Diehl Pascale , Weiss Jean-Jacques , Azouvi Philippe ,   the Members of the Steering Committee of the PariS-TBI Study
Published: March 2012

Background. After a severe traumatic brain injury (TBI), some patients are discharged home without rehabilitation, although rehabilitation is assumed to improve outcome. Objective. To assess factors that predict referral to rehabilitation following acute care. This study is part of a larger inception cohort study assessing the care network in the Parisian area (France). Methods. Between July 2005 and April 2007, 504 adults with severe TBI (Glasgow Coma Scale score ≤8) were prospectively recruited by mobile emergency services. This study included 254 acute care survivors (80% male, median age 32 years). Data regarding demographics, injury severity, and acute care pathway were collected. The first analysis compared patients referred to a rehabilitation facility with patients discharged to a living place. The second analysis compared patients referred to a specialized neurorehabilitation (NR) facility with patients referred to nonspecialized rehabilitation. Univariate and multivariate statistics were computed. Results. In all, 162 patients (64%) were referred to rehabilitation, 115 (45%) of which were referred to NR and 47 (19%) to nonspecialized rehabilitation. The following factors were significantly predictive of nonreferral to rehabilitation: living alone, a lower income professional category, pretraumatic alcohol abuse, lower TBI severity, and transfer through a nonspecialized medical ward before discharge. Patients referred to specialized NR were significantly younger and from a higher income professional category. Conclusions. These results raise concern regarding care pathways because many patients were discharged to living places, probably without adequate assessment and management of rehabilitation needs. Injury severity and social characteristics influenced discharge destination.
Metaphoric language and the articulation of emotions by people affected by motor neurone disease
Authors: Locock Louise , Mazanderani Fadhila , Powell John
Published: March 2012

Objective: To explore the use of metaphoric language to convey emotion in interviews with people affected by motor neurone disease, a progressive neurological condition that sits between chronic and terminal illness.

Methods: Secondary analysis of 46 interviews with people affected by motor neurone disease in the United Kingdom (35 individuals with the condition, 11 carers).

Results: Metaphor and figurative language was used to communicate the intensely emotional experiences of being diagnosed with and living with motor neurone disease. We focus on three pervasive themes that were threaded throughout the interviews: battling and fighting; the self under attack and journeying through a physical and emotional landscape.

Discussion: This secondary analysis of qualitative research interviews enriches our understanding of the articulation of emotion in motor neurone disease and adds to the literature on metaphor in chronic illness. Of particular interest is how the metaphors used contrasted with other conditions in the relative absence of metaphors of ‘fighting’ the disease. Furthermore, we analyse the ways in which participants used metaphors to give voice to emotions that are extremely difficult to articulate in ‘literal’ language, and how, in doing so, they blurred the distinction between ‘physical’ symptoms and ‘emotional’ states. Sensitivity to metaphors may help professionals communicate with people affected by motor neurone disease.
Globalization and people’s interest in foreign affairs
Authors: Lee Francis LF , He Zhou , Lee Chin-chuan , Lin Wanying , Yao Mike Z
Published: March 2012

Globalization signifies the increasing interconnectedness among different parts of the world. But few studies have examined whether and how the processes of globalization relate to people’s interests in foreign affairs. This study tackles the question at the individual level. It identifies transnational social connections, willingness to move abroad, foreign language abilities, and perceived impact of globalization as four factors representing people’s connections with and orientations toward the processes of globalization. These four factors are hypothesized as correlates of people’s interest in foreign affairs. Analysis of a comparative survey ( N = 1117) conducted in Hong Kong and Taipei generally supports the hypotheses, but the results also show that social contexts may shape the strengths of the relationships among different factors. The analysis also explores the problematic of causality. The results suggest that some, but not all, aspects of individuals’ connections with globalization can influence interest in foreign affairs.
Long-term follow-up of periarterial sympathectomy for chronic digital ischaemia
Authors: Murata K. , Omokawa S. , Kobata Y. , Tanaka Y. , Yajima H. , Tamai S.
Published: March 2012

This study investigates long-term clinical results (> 10 years) of periarterial sympathectomy in chronic ischaemic digits compared with intermediate-term results (3 years). Periarterial sympathectomy via the palm and volar wrist was carried out on 11 hands of seven patients with digital ischaemia but no gangrene or severe ulceration. The aetiology of ischaemia was Buerger’s disease in four hands, collagen disease in three hands, and repetitive digital trauma in four hands. Subjective symptoms were evaluated at a mean follow-up period of 12 years. The efficacy of surgery was assessed objectively using thermography and plethysmography. Although five of seven patients continued on oral vasodilators and antiplatelet agents until the final follow-up, improvement of symptoms was maintained in all patients between intermediate- and long-term evaluations. Our results suggest that periarterial sympathectomy via the palm and wrist could prevent long-term aggravation of symptoms of chronic digital ischaemia when combined with adequate postoperative drug therapy.
Load transfer through the radiocarpal joint and the effects of partial wrist arthrodesis on carpal bone behaviour: a finite element study
Authors: Gíslason M. K. , Stansfield B. , Bransby-Zachary M. , Hems T. , Nash D. H.
Published: March 2012

A finite element model of the wrist was developed to simulate mechanical changes that occur after surgery of the wrist. After partial arthrodesis, the wrist will experience altered force transmission during loading. Three different types of partial arthrodesis were investigated — radiolunate, radioscaphoid, and radioscapholunate — and compared with the healthy untreated wrist. The results showed that the compressive forces on the radiocarpal joint decreased compared with the untreated wrist with both radiolunate and radioscaphoid fusions. The load transmission through the midcarpal joints varied depending on arthrodesis type. The forces in the extrinsic ligaments decreased with the fusion, most noticeably in the dorsal radiotriquetral ligament, but increased in the dorsal scaphotriquetral ligament. From the results of the study it can be concluded that the radioscapholunate fusion shows the most biomechanically similar behaviour out of the three fusion types compared with the healthy wrist. The modelling described in this paper may be a useful approach to pre-operative planning in wrist surgery.
Evolution of inflammasome functions in vertebrates: Inflammasome and caspase-1 trigger fish macrophage cell death but are dispensable for the processing of IL-1β
Authors: Angosto Diego , López-Castejón Gloria , López-Muñoz Azucena , Sepulcre María P , Arizcun Marta , Meseguer José , Mulero Victoriano
Published: March 2012

Members of the nucleotide binding and oligomerization domain-like receptors (NLRs) and the PYD and CARD domain containing adaptor protein (PYCARD) assemble into multi-protein platforms, termed inflammasomes, to mediate in the activation of caspase-1 and the subsequent secretion of IL-1β and IL-18, and the induction of pyroptotic cell death. While the recognition site for caspase-1 is well conserved in mammals, most of the non-mammalian IL-1β genes cloned so far lack this conserved site. We report here that stimulation or infection of seabream macrophages (MØ) led to the caspase-1-independent processing and release of IL-1β. In addition, several classical activators of the NLRP3 inflammasome failed to activate caspase-1 and to induce the processing and release of IL-1β. Furthermore, the processing of IL-1β in seabream MØ is not prevented by caspase-1 or pan-caspase inhibitors, and recombinant seabream caspase-1 failed to process IL-1β. However, the pharmacological inhibition of caspase-1 impaired Salmonella enterica sv. Typhimurium-induced cell death. These results suggest a role for the inflammasome and caspase-1 in the regulation of pyroptotic cell death in fish and support the idea that its use as a molecular platform for the processing of pro-inflammatory cytokines arose after the divergence of fish and tetrapods.
The Impact of Ignoring a Level of Nesting Structure in Multilevel Mixture Model
Authors: Chen Qi
Published: March 2012

Mixture modeling has gained more attention among practitioners and statisticians in recent years. However, when researchers analyze their data using finite mixture model (FMM), some may assume that the units are independent of each other even though it may not always be the case. This article used simulation studies to examine the impact of ignoring a higher nesting structure in multilevel mixture models. Results indicate that the misspecification results in lower classification accuracy of individuals, less accurate fixed effect estimates, inflation of lower level variance estimates, and less accurate standard error estimates in each subpopulation, the latter result of which in turn affects the accuracy of tests of significance for the fixed effects. The magnitude of the intraclass correlation (ICC) coefficient has a substantial impact. The implication for applied researchers is that it is important to model the multilevel data structure in mixture modeling.
When democracies kill: Reflections from the US, India, and Northern Ireland
Authors: Davenport Christian
Published: March 2012

Existing research, social movements, nongovernmental organizations, and many national governments herald democracy as a, or perhaps the, resolution to state repression. Interestingly, very little attention has been given to the topic of when democracies kill their citizens for political reasons. Drawing upon insights derived from research in three countries (the United States, India, and Northern Ireland), I focus on three strategies that democratic governments use to facilitate their use of violent repressive behavior. These highlight not only areas for subsequent investigation as the world turns to political democracy as the dominant form of regime type but also have implications for those calling for democratic governments as well. Indeed, it may be useful to develop a new phrase as everyone’s political dreams/aspirations come true: ‘Caveat Civis’ – citizens beware.
Active citation through hyperlinks: The retarded replication revolution
Authors: Tønnesson Stein
Published: March 2012

The hyperlink revolution in academic referencing is long overdue. Why is the potential offered by the internet for providing hyperlinks to sources so little utilized by scholars? The article discusses the most likely reasons and suggests that the revolution will happen only when it is promoted from above through mandatory hyperlinks in term papers, dissertations, journal articles and scholarly monographs. This will make it possible for readers to replicate, test and evaluate not just statistical analyses of quantifiable data, but any argument based on qualitative or quantitative analysis of any kind of source, be it an object, text, speech act, image, or film.
Multiple myeloma exhibits novel dependence on GLUT4, GLUT8, and GLUT11: implications for glucose transporter-directed therapy
Authors: McBrayer Samuel K. , Cheng Javelin C. , Singhal Seema , Krett Nancy L. , Rosen Steven T. , Shanmugam Mala
Published: March 2012

Multiple myeloma is one of numerous malignancies characterized by increased glucose consumption, a phenomenon with significant prognostic implications in this disease. Few studies have focused on elucidating the molecular underpinnings of glucose transporter (GLUT) activation in cancer, knowledge that could facilitate identification of promising therapeutic targets. To address this issue, we performed gene expression profiling studies involving myeloma cell lines and primary cells as well as normal lymphocytes to uncover deregulated GLUT family members in myeloma. Our data demonstrate that myeloma cells exhibit reliance on constitutively cell surface-localized GLUT4 for basal glucose consumption, maintenance of Mcl-1 expression, growth, and survival. We also establish that the activities of the enigmatic transporters GLUT8 and GLUT11 are required for proliferation and viability in myeloma, albeit because of functionalities probably distinct from whole-cell glucose supply. As proof of principle regarding the therapeutic potential of GLUT-targeted compounds, we include evidence of the antimyeloma effects elicited against both cell lines and primary cells by the FDA-approved HIV protease inhibitor ritonavir, which exerts a selective off-target inhibitory effect on GLUT4. Our work reveals critical roles for novel GLUT family members and highlights a therapeutic strategy entailing selective GLUT inhibition to specifically target aberrant glucose metabolism in cancer.
Rational design and characterization of platelet factor 4 antagonists for the study of heparin-induced thrombocytopenia
Authors: Sachais Bruce S. , Rux Ann H. , Cines Douglas B. , Yarovoi Serge V. , Garner Lee I. , Watson Stephen P. , Hinds Jillian L. , Rux John J.
Published: March 2012

Patients with heparin-induced thrombocytopenia (HIT) remain at risk for recurrent thromboembolic complications despite improvements in management. HIT is caused by antibodies that preferentially recognize ultralarge complexes (ULCs) of heparin and platelet factor 4 (PF4) tetramers. We demonstrated previously that a variant PF4K50E forms dimers but does not tetramerize or form ULCs. Here, we identified small molecules predicted to bind PF4 near the dimer-dimer interface and that interfere with PF4 tetramerization. Screening a library of small molecules in silico for binding at this site, we identified 4 compounds that inhibited tetramerization at micromolar concentrations, designated PF4 antagonists (PF4As). PF4As also inhibited formation of pathogenic ULCs, and 3 of these PF4As promoted the breakdown of preformed ULCs. To characterize the ability of PF4As to inhibit cellular activation, we developed a robust and reproducible assay that measures cellular activation by HIT antibodies via FcγRIIA using DT40 cells. PF4As inhibit FcγRIIA-dependent activation of DT40 cells by HIT antibodies as well as platelet activation, as measured by serotonin release. PF4As provide new tools to probe the pathophysiology of HIT. They also may provide insight into the development of novel, disease-specific therapeutics for the treatment of thromboembolic complications in HIT.
Strong convergence theorems by Halpern-Mann iterations for multi-valued relatively nonexpansive mappings in Banach spaces with applications
Authors: Zhu Jin-hua , Chang Shih-sen , Liu Min
Published: March 2012

In this article, an iterative sequence for relatively nonexpansive multi-valued mapping by modifying Halpern and Mann's iterations is introduced, and then some strong convergence theorems are proved. At the end of the article some applications are given also.

AMS Subject Classification: 47H09; 47H10; 49J25.
Identification of microRNAs from Amur grape (vitis amurensis Rupr.) by deep sequencing and analysis of microRNA variations with bioinformatics
Authors: Wang Chen , Han Jian , Liu Chonghuai , Kibet Korir Nicholas , Kayesh Emrul , Shangguan Lingfei , Li Xiaoying , Fang Jinggui
Published: March 2012

Background

MicroRNA (miRNA) is a class of functional non-coding small RNA with 19-25 nucleotides in length while Amur grape (Vitis amurensis Rupr.) is an important wild fruit crop with the strongest cold resistance among the Vitis species, is used as an excellent breeding parent for grapevine, and has elicited growing interest in wine production. To date, there is a relatively large number of grapevine miRNAs (vv-miRNAs) from cultivated grapevine varieties such as Vitis vinifera L. and hybrids of V. vinifera and V. labrusca, but there is no report on miRNAs from Vitis amurensis Rupr, a wild grapevine species.

Results

A small RNA library from Amur grape was constructed and Solexa technology used to perform deep sequencing of the library followed by subsequent bioinformatics analysis to identify new miRNAs. In total, 126 conserved miRNAs belonging to 27 miRNA families were identified, and 34 known but non-conserved miRNAs were also found. Significantly, 72 new potential Amur grape-specific miRNAs were discovered. The sequences of these new potential va-miRNAs were further validated through miR-RACE, and accumulation of 18 new va-miRNAs in seven tissues of grapevines confirmed by real time RT-PCR (qRT-PCR) analysis. The expression levels of va-miRNAs in flowers and berries were found to be basically consistent in identity to those from deep sequenced sRNAs libraries of combined corresponding tissues. We also describe the conservation and variation of va-miRNAs using miR-SNPs and miR-LDs during plant evolution based on comparison of orthologous sequences, and further reveal that the number and sites of miR-SNP in diverse miRNA families exhibit distinct divergence. Finally, 346 target genes for the new miRNAs were predicted and they include a number of Amur grape stress tolerance genes and many genes regulating anthocyanin synthesis and sugar metabolism.

Conclusions

Deep sequencing of short RNAs from Amur grape flowers and berries identified 72 new potential miRNAs and 34 known but non-conserved miRNAs, indicating that specific miRNAs exist in Amur grape. These results show that a number of regulatory miRNAs exist in Amur grape and play an important role in Amur grape growth, development, and response to abiotic or biotic stress.
Epigenetic features are significantly associated with alternative splicing
Authors: Zhou Yuanpeng , Lu Yulan , Tian Weidong
Published: March 2012

Background

While alternative splicing (AS) contributes greatly to protein diversities, the relationship between various types of AS and epigenetic factors remains largely unknown.

Results

In this study, we discover that a number of epigenetic features, including DNA methylation, nucleosome occupancy, specific histone modifications and protein features, are strongly associated with AS. To further enhance our understanding of the association between these features and AS, we cluster our investigated features based on their association patterns with each AS type into four groups, with H3K36me3, EGR1, GABP, SRF, SIN3A and RNA Pol II grouped together and showing strongest association with AS. In addition, we find that the AS types can be classified into two general classes, namely the exon skipping related process (ESRP), and the alternative splice site selection process (ASSP), based on their association levels with the epigenetic features.

Conclusion

Our analysis thus suggests that epigenetic features are likely to play important roles in regulating AS.
Characterization and gene expression analysis of the cir multi-gene family of plasmodium chabaudi chabaudi (AS)
Authors: Lawton Jennifer , Brugat Thibaut , Yan Yam Xue , Reid Adam James , Böhme Ulrike , Otto Thomas Dan , Pain Arnab , Jackson Andrew , Berriman Matthew , Cunningham Deirdre , Preiser Peter , Langhorne Jean
Published: March 2012

Background

Thepirgenes comprise the largest multi-gene family inPlasmodium, with members found inP. vivax, P. knowlesiand the rodent malaria species. Despite comprising up to 5% of the genome, little is known about the functions of the proteins encoded bypirgenes.P. chabaudicauses chronic infection in mice, which may be due to antigenic variation. In this model,pirgenes are calledcirs and may be involved in this mechanism, allowing evasion of host immune responses. In order to fully understand the role(s) of CIR proteins duringP. chabaudiinfection, a detailed characterization of thecirgene family was required.

Results

Thecirrepertoire was annotated and a detailed bioinformatic characterization of the encoded CIR proteins was performed. Two major sub-families were identified, which have been named A and B. Members of each sub-family displayed different amino acid motifs, and were thus predicted to have undergone functional divergence. In addition, the expression of the entirecirrepertoire was analyzed via RNA sequencing and microarray. Up to 40% of thecirgene repertoire was expressed in the parasite population during infection, and dominantcirtranscripts could be identified. In addition, some differences were observed in the pattern of expression between thecirsubgroups at the peak ofP. chabaudiinfection. Finally, specificcirgenes were expressed at different time points during asexual blood stages.

Conclusions

In conclusion, the large number ofcirgenes and their expression throughout the intraerythrocytic cycle of development indicates that CIR proteins are likely to be important for parasite survival. In particular, the detection of dominantcirtranscripts at the peak ofP. chabaudiinfection supports the idea that CIR proteins are expressed, and could perform important functions in the biology of this parasite. Further application of the methodologies described here may allow the elucidation of CIR sub-family A and B protein functions, including their contribution to antigenic variation and immune evasion.
Breast cancer stage at diagnosis and area-based socioeconomic status: a multicenter 10-year retrospective clinical epidemiological study in China
Authors: Wang Qiong , Li Jing , Zheng Shan , Li Jia-Yuan , Pang Yi , Huang Rong , Zhang Bao-Ning , Zhang Bin , Yang Hong-Jian , Xie Xiao-Ming , Tang Zhong-Hua , Li Hui , He Jian-Jun , Fan Jin-Hu , Qiao You-Lin
Published: March 2012

Background

Although socioeconomic status (SES) has been focused on as a key determinant of cancer stage at diagosis in western countries, there has been no systemic study on the relationship of SES and breast cancer stage at diagnosis in China.

Methods

The medical charts of 4,211 eligible breast cancer patients from 7 areas across China who were diagnosed between 1999 and 2008 were reviewed. Four area-based socioeconomic indicators were used to calculate area-based SES by cluster analysis. The associations between area-based SES and stage at diagnosis were analyzed by trend chi-square tests. Binary logistic regression was performed to estimate odds ratios for individual demographic characteristics' effects on cancer stages, stratified by area-based SES.

Results

The individual demographic and pathologic characteristics of breast cancer cases were significantly different among the seven areas studied. More breast cancer cases in low SES areas (25.5%) were diagnosed later (stages III & IV) than those in high (20.4%) or highest (14.8%) SES areas (χ
2 for trend = 80.79, P < 0.001). When area-based SES is controlled for, in high SES areas, cases with less education were more likely to be diagnosed at later stages compared with more educated cases. In low SES areas, working women appeared to be diagnosed at earlier breast cancer stages than were homemakers (OR: 0.18-0.26).

Conclusions

In China, women in low SES areas are more likely to be diagnosed at later breast cancer stages than those in high SES areas.
Methylation profiling of Epstein-Barr virus immediate-early gene promoters, BZLF1 and BRLF1in tumors of epithelial, NK- and B-cell origins
Authors: Li Lili , Su Xianwei , Choi Gigi Ching Gee , Cao Ya , Ambinder Richard F , Tao Qian
Published: March 2012

Background

Epstein-Barr virus (EBV) establishes its latency in EBV-associated malignancies, accompanied by occasionally reactivated lytic cycle. Promoter CpG methylation of EBV genome plays an essential role in maintaining viral latency. Two immediate-early (IE) genes, BZLF1 and BRLF1, induce the switch from latent to lytic infection. Studies of methylation-dependent binding of BZLF1 and BRLF1 to EBV promoters have been well reported, but little is known about the methylation status of BZLF1 and BRLF1 promoters (Zp and Rp) in tumor samples.

Methods

We evaluated the methylation profiles of Zp and Rp by methylation-specific PCR (MSP) and bisulfite genomic sequencing (BGS), as well as BZLF1 and BRLF1 expression by semiquantitative reverse transcription (RT)-PCR in tumors of epithelial, NK- and B-cell origins.

Results

We found that both Zp and Rp were hypermethylated in all studied EBV-positive cell lines and tumors of lymphoid (B- or NK cell) or epithelial origin, while unmethylated Zp and Rp alleles were detected in cell lines expressing BZLF1 and BRLF1. Following azacytidine treatment or combined with trichostatin A (TSA), the expression of BZLF1 and BRLF1 was restored along with concomitant promoter demethylation, which subsequently induced the reactivation of early lytic gene BHRF1 and late lytic gene BLLF1.

Conclusions

Hypermethylation of Zp and Rp mediates the frequent silencing of BZLF1 and BRLF1 in EBV-associated tumors, which could be reactivated by demethylation agent and ultimately initiated the EBV lytic cascade.