bluuebunny/crossref_metadata_2025 huggingface dataset:
Expanded CD23+/CD21hi B Cells in Inflamed Lymph Nodes Are Associated with the Onset of Inflammatory-Erosive Arthritis in TNF-Transgenic Mice and Are Targets of Anti-CD20 Therapy
Authors: Li Jie , Kuzin Igor , Moshkani Safiehkhatoon , Proulx Steven T. , Xing Lianping , Skrombolas Denise , Dunn Robert , Sanz Iñaki , Schwarz Edward M. , Bottaro Andrea
Published: May 2010

Anti-CD20 B cell depletion therapy (BCDT) is very effective for some patients with rheumatoid arthritis (RA); however the pathogenic role of B lymphocytes in RA and the primary targets of BCDT are unknown. The human TNF transgenic (hTNF-Tg) mouse model of RA displays a chronic, progressive disease that spreads from distal to proximal joints and is generally considered to be adaptive immune system independent. We have previously reported that knee arthritis in hTNF-Tg mice is accompanied by structural and functional changes of the adjoining popliteal lymph node (PLN), detectable by contrast-enhanced magnetic resonance imaging. To better understand these changes, in this paper we show that onset of knee synovitis and focal erosions are paralleled by PLN contraction and accumulation of large numbers of B cells in the lymphatic sinus spaces within the node. Flow cytometry from TNF-Tg mice 2, 4–5, and 8–12 mo old demonstrated that B cell accumulation in the PLN follows ankle arthritis, but commences before knee disease, and involves early expansion of CD21hi, CD23+, IgMhi, CD1d+, activation marker-negative, polyclonal B cells that are found to be specifically restricted to lymph nodes draining inflamed, arthritic joints. The same B cell population also accumulates in PLNs of K/BxN mice with autoantigen-dependent arthritis. Strikingly, we show that BCDT ameliorates hTNF-Tg disease and clears follicular and CD21hi, CD23+ B cells from the PLNs. On the basis of these findings, we propose a model whereby B cells contribute to arthritis in mice, and possibly RA, by directly affecting the structure, composition, and function of joint-draining lymph nodes.
Polyfunctional CD4+ and CD8+ T Cell Responses to Tuberculosis Antigens in HIV-1–Infected Patients before and after Anti-Retroviral Treatment
Authors: Sutherland Jayne S. , Young James M. , Peterson Kevin L. , Sanneh Bakary , Whittle Hilton C. , Rowland-Jones Sarah L. , Adegbola Richard A. , Jaye Assan , Ota Martin O. C.
Published: May 2010

Tuberculosis (TB) kills 2 million people per year and infection with HIV is the most potent known risk factor for progression to active TB. An understanding of the immune response to TB Ags in HIV-infected patients is required to develop optimal TB vaccines and diagnostics. We assessed polyfunctional (IFN-γ+IL-2+TNF-α+) T cell responses to TB Ags in three groups of HIV-1–infected patients dependent on their TB status, CD4 counts, and anti-retroviral exposure. We found that although the proportion of IFN-γ cells in response to TB Ags was higher in patients with low CD4 counts, the responding cells changed from a polyfunctional CD4+ to a monofunctional CD8+ response. The overall polyfunctionality of the cells was restored by 12 mo of anti-retroviral therapy and primarily involved CD4+ T cells with an effector memory phenotype. These findings have major implications for diagnosis of TB and in vaccine development strategies for TB in HIV-1–infected patients.
Cutting Edge: Rag Deletion in Peripheral T Cells Blocks TCR Revision
Authors: Hale J. Scott , Ames Kristina T. , Boursalian Tamar E. , Fink Pamela J.
Published: May 2010

Mature CD4+Vβ5+ T cells that recognize a peripherally expressed endogenous superantigen are tolerized either by deletion or TCR revision. In Vβ5 transgenic mice, this latter tolerance pathway results in the appearance of CD4+Vβ5−TCRβ+ T cells, coinciding with Rag1, Rag2, and TdT expression and the accumulation of Vβ-DJβ recombination intermediates in peripheral CD4+ T cells. Because postthymic RAG-dependent TCR rearrangement has remained controversial, we sought to definitively determine whether TCR revision is an extrathymic process that occurs in mature peripheral T cells. We show in this study that Rag deletion in postpositive selection T cells in Vβ5 transgenic mice blocks TCR revision in vivo and that mature peripheral T cells sorted to remove cells bearing endogenous TCRβ-chains can express newly generated TCRβ molecules in adoptive hosts. These findings unambiguously demonstrate postthymic, RAG-dependent TCR rearrangement and define TCR revision as a tolerance pathway that targets mature peripheral CD4+ T cells.
Maximizing the Benefits of ERP Systems
Authors: Menezes Paulo André Da Conceiçao , Ladrón de Guevara Fernando González
Published: May 2010

The ERP (Enterprise Resource Planning) systems have been consolidated in companies with different sizes and sectors, allowing their real benefits to be definitively evaluated. In this study, several interactions have been studied in different phases, such as the strategic priorities and strategic planning defined as ERP Strategy; business processes review and the ERP selection in the pre-implementation phase, the project management and ERP adaptation in the implementation phase, as well as the ERP revision and integration efforts in the post-implementation phase. Through rigorous use of case study methodology, this research led to developing and to testing a framework for maximizing the benefits of the ERP systems, and seeks to contribute for the generation of ERP initiatives to optimize their performance.
Knowledge Appropriation Between Private Education Institutions: Cupi2 Project Transfer from Uniandes to Uniminuto
Authors: Herrera Cubides Jhon Francined , Giraldo Velez Olga Lucia
Published: May 2010

Strategic alliances are critical to generate competitive advantage in organizations. One type of such alliances is knowledge transfer. Knowledge transfer goes beyond transfer between enterprises, involves appropriating and adapting to organizational environment and characteristics, using resources of its own resources and form strategic allied. Beyond a simple organizational benchmarking, knowledge transfer will strengthen existing knowledge and generate new knowledge within organization partnerships, complementing learning in organizations. This paper presents a guide to transfer knowledge between private education institutions and its application to transfer a teaching programming methodology, the CUPI2 project, between Universidad de los Andes –UNIANDES and Corporación Universitaria Minuto de Dios –UNIMINUTO, both located in Bogota, Colombia. To achieve our objective we present, as foundation, knowledge management applied to education environments and participants in the CUPI2 transfer process. We present the guide, its current state of application, how we plan to continue it, and the main conclusions we have attained.
Adoption of Technological Innovations in the Field of Health: a Study on Information Systems in the Perspective of the Theory of Diffusion
Authors: Perez Gilberto , Zwicker Ronaldo , Zilber Moisés Ari , Júnior Alberto de Medeiros
Published: May 2010

This paper identifies some factors which contribute for the adoption of a Technological Innovation (Systems of Information) in the health area and also identifies the way some internal groups are acting towards the adoption (and use) or rejection of a technological innovation. It has researched into an Electronic Patient Record system in an Emergency Ward and a Teaching Support System by Web in a Medicine College. Two pieces of field qualitative research have been carried out through adopting the technique of exploratory nature, conducted by interviews-in-depth with the main managers and key-users which influence the adoption of the innovation. The research outcome indicates (among other aspects), that the channels used for spreading innovation, for spreading the performance of change providers agents and the preparation for change are aspects that definitely determine the adoption of information systems in the health area.
Monitoring Environmental Liabilities with Support of the Technology and Information System
Authors: Tachizawa Takeshy
Published: May 2010

It presents an architecture of data for diagnosis of social costs of organizations in terms of economic sustainability. It proposed a model of the database of indicators of social differentiation of costs, based on empirical research, developed the method grounded theory. The emphasis of grounded theory is that learning from the data (interactive and inductive), and not from a theoretical vision existing (deductive). Such indicators, and reflect the stage of sustainability where the company tested, sinalyzing the mapping of different socio economic segments of the Brazilian business universe. The architecture, structured with the support of information technology resources would allow the planning decisions inherent in the management of social costs of their production chain.
R&D Entities and Strategic Tracking Systems: an Analysis of the Methodologies Used
Authors: Cardoso Ricardo Lopes , Neto Octavio Ribeiro de Mendonça
Published: May 2010

This paper’s main purposes are to analyze the research centers strategic performance measurement system; to study what methodologies are more commonly used and to find out how measurement system and strategic goals are integrated. The sample consists of six research centers in Campinas – São Paulo and the theoretical backgrounds used are the strategic performance measurement systems like the Tableau de Bord, the Sink and Tuttle model and the Kaplan and Norton’s Balanced Scorecard. The research results were subject to qualitative analysis leading to the following considerations: research centers measure, assess and monitor their results with strategic drivers systems mainly through qualitative dimensions such as research, development and innovation, customer satisfaction – users and services and processes quality. Among the systems used, the specific ones prevail and half of them are conceptually linked with the Balanced Scorecard content. The final research results demonstrate great lack of integration between the strategic plans and the performance indicators as well as lack of integration between the performance indicators and the organization as a whole.
Fuzzy Logic Application for Economical-Financial Performance Evaluation of Production Cooperatives.
Authors: Khatchatourian Oleg , Treter Jaciara
Published: May 2010

In this work a methodology based on Fuzzy Logic was developed for classification and evaluation of Economical-financial Performance of production cooperatives. Continuous scales were introduced and Fuzzy Logic based sub-models, were created to evaluate Own Capital Return, Payment Capacity and Capital Structure of a production cooperative. By applying the developed model, the Performance dynamics of two production cooperatives (Coopermil and Cotricampo) was analyzed in a 5 year’s period.. Evaluations carried out through numeric simulation in order to analyse the influence of several indicators on a production cooperative performance and expert evaluations showed good correlation.
Neural Networks, Fuzzy Logic and Genetic Algorithms: Applications and Possibilities in Finance and Accounting
Authors: Wuerges Artur Filipe Ewald , Borba José Alonso
Published: May 2010

There are problems in Finance and Accounting that can not be easily solved by means of traditional techniques (e.g. bankruptcy prediction and strategies for investing in common stock). In these situations, it is possible to use methods of Artificial Intelligence. This paper analyzes empirical works published in international journals between 2000 and 2007 that present studies about the application of Neural Networks, Fuzzy Logic and Genetic Algorithms to problems in Finance and Accounting. The objective is to identify and quantify the relationships established between the available techniques and the problems studied by the researchers. Analyzing 258 papers, it was noticed that the most used technique is the Artificial Neural Network. The most researched applications are from the field of Finance, especially those related to stock exchanges (forecasting of common stock and indices prices).
Knowledge Sharing Contribution to Project Risk Management: a Study in the Software Industry
Authors: Souza Yóris Linhares , Vasconcelos Maria Celeste Reis Lobo , Judice Valéria Maria Martins , Jamil George Leal
Published: May 2010

A study was conducted in the aim to identify whether and how knowledge sharing contributes, through instruments and behavioral aspects, to risk management. Initially, as the literature review was carried out, it was identified, on one hand, the main instruments and behavioral aspects that facilitate knowledge sharing and, on the other hand, the different approaches to risk management in software projects. Following that, the relationship between these two themes was established. Then, based on a case study in the software industry, an analysis was carried out and applied to the development teams, aiming at understanding and perceiving what risk management activities are practiced in software projects, the behavioral factors that may favorably influence knowledge sharing on software projects risks and what instruments of knowledge sharing may contribute, at a certain degree, to risk management in projects.
Tacit, Explicit, and Cultural Knowledge in Demand Planning
Authors: POPADIUK SILVIO , SANTOS ANDRÉ EDUARDO  MIRANDA DOS
Published: May 2010

Demand planning consists in a set of steps which evolves two main types of knowledge: tacit and explicit. It is under these types of knowledge that the present article was developed. It aimed at relating the concept of demand planning with knowledge management, but delimited to its tacit, explicit, and cultural knowledge components. An exploratory research was done with five companies. Therefore, the study was characterized as multicases and evolded enterviews, observations, and documents analysis. The analysis was made by content analysis. The results evidenced the presence of a set of components related to the three types of knowledge in demand planning like: information technology tools, professional experience, collective interation, social relations, and a corporative view, which leads the company´ business.
Efficient modelling of IC conducted emission for power integrity analysis
Authors: Kazemzadeh R. , Ludwig S. , Radić-Weissenfeld Lj. , Mathis W.
Published: April 2010

Abstract. In this paper two methodologies to reduce the complexity of IC conducted emission models for Power Integrity analysis in ICs are presented. The methodologies differ concerning the applicability in simulation tools, complexity and accuracy of the generated models. The first methodology uses a complex model and reduces its order to generate a model with a fewer number of elements. This methodology therefore involves a model order reduction approach. A second minimum complexity, module based modelling approach is introduced for rough estimations, as the order reduced model is still too complex for some applications. The two methodologies are applied to an IC conducted emission model of two digital modules of a 32 Bit microcontroller. The results of the three models are compared and discussed. Fields of application for the introduced modelling approaches are the estimation of the magnitude and time behaviour of the supply current as well as the determination of the number and position of the IC's supply pins.
Importance of immobilization after intraarticular glucocorticoid treatment for elbow synovitis: A randomized controlled study
Authors: Weitoft Tomas , Forsberg Catarina
Published: April 2010

Objective

To investigate whether better treatment results might be achieved with postinjection rest following intraarticular glucocorticoid treatment for elbow synovitis.

Methods

Ninety patients with rheumatoid arthritis and elbow synovitis were treated with 20 mg of intraarticular triamcinolone hexacetonide and randomized to either a 48‐hour immobilization in a triangular sling (n = 46) or to normal activity without restrictions (n = 44). The primary end point was relapse of synovitis. In addition, pain, function according to a self‐assessment questionnaire (the Patient Rated Elbow Evaluation), and range of movement were followed for 6 months.

Results

Thirteen relapses occurred in the rest group and 8 in the active group (results not significant). The secondary measures showed no statistically significant differences between the groups.

Conclusion

Immobilization procedures do not improve the outcome of intraarticular glucocorticoid therapy for elbow synovitis. In future guidelines for such treatment of the upper extremity, normal activity after the injection should be recommended.
Benefit of early treatment in inflammatory polyarthritis patients with anti–cyclic citrullinated peptide antibodies versus those without antibodies
Authors: Farragher Tracey M. , Lunt Mark , Plant Darren , Bunn Diane K. , Barton Anne , Symmons Deborah P. M.
Published: April 2010

Objective

To compare the clinical utility of anti–cyclic citrullinated peptide (anti‐CCP) antibodies and rheumatoid factor (RF) testing in predicting both functional outcome and response to treatment in early inflammatory polyarthritis (IP) patients.

Methods

A total of 916 IP subjects from a primary care incidence registry (1990–1994) had anti‐CCP antibody and RF status determined at baseline. Mean change in Health Assessment Questionnaire (HAQ) score between baseline and 5 years was compared by antibody status. The effect of treatment with disease‐modifying antirheumatic drugs and/or steroids over 5 years, early (<6 months of symptom onset) versus late initiation, and duration of treatment were also compared by anti‐CCP antibody status. The analysis was adjusted for treatment decisions and censoring over the followup, using marginal structural models.

Results

Anti‐CCP antibody–positive patients (n = 268) had more severe disease both at presentation and 5 years of followup, and this was independent of RF. On adjustment, anti‐CCP antibody–negative patients treated early experienced a significant improvement in functional disability compared with anti‐CCP antibody–negative patients who were never treated (−0.31; 95% confidence interval [95% CI] −0.53, −0.08), and experienced additional benefit for each additional month of early treatment. Anti‐CCP antibody–positive patients treated early did not have a significant improvement in HAQ score compared with those not treated (−0.14; 95% CI −0.52, 0.24).

Conclusion

In this first observational study to examine the influence of anti‐CCP antibody status on treatment response, anti‐CCP antibody–positive IP patients showed less benefit from treatment, particularly early treatment, than anti‐CCP antibody–negative patients. This provides support for the inclusion of anti‐CCP antibodies as well as RF in the classification criteria for rheumatoid arthritis and for stratification by anti‐CCP antibody status in clinical trials.
Chemically Derived Graphene Oxide: Towards Large‐Area Thin‐Film Electronics and Optoelectronics
Authors: Eda Goki , Chhowalla Manish
Published: April 2010

Chemically derived graphene oxide (GO) possesses a unique set of properties arising from oxygen functional groups that are introduced during chemical exfoliation of graphite. Large‐area thin‐film deposition of GO, enabled by its solubility in a variety of solvents, offers a route towards GO‐based thin‐film electronics and optoelectronics. The electrical and optical properties of GO are strongly dependent on its chemical and atomic structure and are tunable over a wide range via chemical engineering. In this Review, the fundamental structure and properties of GO‐based thin films are discussed in relation to their potential applications in electronics and optoelectronics.
Are immigrants, ethnic and linguistic minorities over‐represented in jobs with a high level of compensated risk? Results from a montréal, Canada study using census and workers' compensation data
Authors: Premji Stéphanie , Duguay Patrice , Messing Karen , Lippel Katherine
Published: April 2010

Objectives

Few Canadian data sources allow the examination of disparities by ethnicity, language, or immigrant status in occupational exposures or health outcomes. However, it is possible to document the mechanisms that can create disparities, such as the over‐representation of population groups in high‐risk jobs. We evaluated, in the Montréal context, the relationship between the social composition of jobs and their associated risk level.

Methods

We used data from the 2001 Statistics Canada census and from Québec's workers' compensation board for 2000–2002 to characterize job categories defined as major industrial groups crossed with three professional categories (manual, mixed, non‐manual). Immigrant, visible, and linguistic minority status variables were used to describe job composition. The frequency rate of compensated health problems and the average duration of compensation determined job risk level. The relationship between the social composition and risk level of jobs was evaluated with Kendall correlations.

Results

The proportion of immigrants and minorities was positively and significantly linked to the risk level across job categories. Many relationships were significant for women only. In analyses done within manual jobs, relationships with the frequency rate reversed and were significant, except for the relationship with the proportion of individuals with knowledge of French only, which remained positive.

Conclusions

Immigrants, visible, and linguistic minorities in Montréal are more likely to work where there is an increased level of compensated risk. Reversed relationships within manual jobs may be explained by under‐reporting and under‐compensation in vulnerable populations compared to those with knowledge of the province's majority language. Am. J. Ind. Med. 53:875–885, 2010. © 2010 Wiley‐Liss, Inc.
Racial and ethnic disparities in work‐related injuries and socio‐economic resources among nursing assistants employed in US nursing homes
Authors: Tak SangWoo , Alterman Toni , Baron Sherry , Calvert Geoffrey M.
Published: April 2010

Background

We aimed to estimate the proportion of nursing assistants (NAs) in the US with work‐related injuries and insufficient socio‐economic resources by race/ethnicity.

Methods

Data from the 2004 National Nursing Assistant Survey (NNAS), a nationally representative sample survey of NAs employed in United States nursing homes, were analyzed accounting for the complex survey design.

Results

Among 2,880 participants, 44% reported “scratch, open wounds, or cuts” followed by “back injuries” (17%), “black eyes or other types of bruising” (16%), and “human bites” (12%). When compared to non‐Hispanic white NAs, the adjusted rate ratio (RR) for wound/cut was 0.74 for non‐Hispanic black NAs (95% confidence interval [CI]: 0.65–0.85). RRs for black eyes/bruises were 0.18 for non‐Hispanic black NAs (95% CI: 0.12–0.26), and 0.55 for Hispanic NAs (95% CI: 0.37–0.82).

Conclusions

Minority racial and ethnic groups were less likely to report having experienced injuries compared with non‐Hispanic white NAs. Future research should focus on identifying preventable risk factors, such as differences by race and ethnicity in the nature of NA jobs and the extent of their engagement in assisting patients with activities of daily living. Am. J. Ind. Med. 53:951–959, 2010. © 2010 Wiley‐Liss, Inc.
Further investigation of the association between rs7341475 and rs17746501 and schizophrenia
Authors: Ben‐David Eyal ,   The International Schizophrenia Consortium, Shifman Sagiv
Published: April 2010

Genome‐wide association studies (GWAS) with small sample size have had limited statistical power in identifying schizophrenia susceptibility genes. This is exemplified by the fact that one of the most convincing associations was detected only after meta‐analyses of three different GWAS. Here we used meta‐analysis to study the association of two single‐nucleotide polymorphisms (SNPs) (rs7341475 and rs17746501) previously indicated to be associated with schizophrenia by a GWAS of Ashkenazi Jews (AJ). In the initial report, rs7341475 was associated only in women, while rs17746501 was associated in both men and women. We collected genotyping results of samples published in four GWAS for the two SNPs, additional to results from AJ. We used the Mantel–Haenszel method to combine the data of the different samples. For both SNPs, the results of the meta‐analysis of all samples, including the initial report, did not reach a genome‐wide significance level. However, the association between rs7341475 and schizophrenia in women, after excluding the data from AJ, was significant (P = 9.0 × 10−3), with a calculated odds ratio (OR) of 1.11, much smaller than the original result. Association between rs17746501 and schizophrenia was significant in four of the new samples, showing evidence for heterogeneity and very small effect when tested across all samples (P = 0.016, OR = 1.06). These findings suggest that the two SNPs might have a small effect on schizophrenia risk and suggest that meta‐analyses of very large samples are needed to adequately study the contribution of common variants to schizophrenia susceptibility. © 2010 Wiley‐Liss, Inc.
Field primatology of today: current ethical issues
Authors: MacKinnon K.C. , Riley E.P.
Published: April 2010

As members of professional organizations such as American Society of Primatologists (ASP) and the International Primatological Society (IPS), primatologists must adhere to a set of nonhuman primate‐focused principles outlined in resolutions and policy statements on, for example, the ethical treatment of nonhuman primates. Those of us that work in the field must also address issues such as the protection of primate health in the wild and the conservation of wild primate populations. Moreover, we increasingly find ourselves in complex situations where we must balance human and nonhuman primate needs and interests. The selection of commentary pieces in this edition of the American Journal of Primatology originated from presentations given in the symposium, Field Primatology of Today: Navigating the Ethical Landscape, held at the 32nd Annual Meeting of the American Society of Primatologists (ASP) in September 2009. The goals of that symposium and these resulting commentary pieces are threefold: (1) to revive a discussion of key contemporary ethical issues faced by field primatologists, (2) to highlight the need for centrally placed ethical considerations in various facets of our professional lives, particularly research and teaching, and (3) to consider what a comprehensive ethical code that addresses all of these issues might look like. Am. J. Primatol. 72:749–753, 2010. © 2010 Wiley‐Liss, Inc.
Putting the community back in community ecology and education: the role of field schools and private reserves in the ethical training of primatologists
Authors: Garber P.A. , Molina A. , Molina R.L.
Published: April 2010

In 1993 and 1999, with the assistance of a Nicaraguan family, we founded La Suerte Biological Research Station in northeastern Costa Rica and Ometepe Biological Research Station in southern Nicaragua as a privately owned conservation‐oriented business. Our goal was to develop a program of sustainable community ecology focused on education, research, and the conservation of primates and tropical forests. In order to accomplish this we developed field courses in which undergraduate and graduate students conduct scientific research, experience local cultures, and learn about conservation. Over 120 of these students have received doctoral degrees or are currently in graduate programs. Four doctoral dissertations, several MA theses, and some 20 scientific articles have been published based on research conducted at our field stations. In order to achieve our long‐term goals of preserving the environment, we also needed to engage directly with local communities to address their needs and concerns. To this end, we developed a series of community‐based initiatives related to health care, bilingual education, and conservation education using traditional and on‐line teaching tools. In this article, we describe our efforts in Costa Rica and Nicaragua teaching conservation‐oriented field courses and working with the local human communities. Building upon these experiences, we outline a set of ethical considerations and responsibilities for private reserves, conservation‐oriented businesses, NGOs, and conservancies that help integrate members of the local community as stakeholders in conservation. Am. J. Primatol. 72:785–793, 2010. © 2010 Wiley‐Liss, Inc.
Thalamic sensitization transforms localized pain into widespread allodynia
Authors: Burstein Rami , Jakubowski Moshe , Garcia‐Nicas Esther , Kainz Vanessa , Bajwa Zahid , Hargreaves Richard , Becerra Lino , Borsook David
Published: April 2010

Objective

Focal somatic pain can evolve into widespread hypersensitivity to nonpainful and painful skin stimuli (allodynia and hyperalgesia, respectively). We hypothesized that transformation of headache into whole‐body allodynia/hyperalgesia during a migraine attack is mediated by sensitization of thalamic neurons that process converging sensory impulses from the cranial meninges and extracephalic skin.

Methods

Extracephalic allodynia was assessed using single unit recording of thalamic trigeminovascular neurons in rats and contrast analysis of blood oxygenation level‐dependent (BOLD) signals registered in functional magnetic resonance imaging (fMRI) scans of patients exhibiting extracephalic allodynia.

Results

Sensory neurons in the rat posterior thalamus that were activated and sensitized by chemical stimulation of the cranial dura exhibited long‐lasting hyperexcitability to innocuous (brush, pressure) and noxious (pinch, heat) stimulation of the paws. Innocuous, extracephalic skin stimuli that did not produce neuronal firing at baseline (eg, brush) became as effective as noxious stimuli (eg, pinch) in eliciting large bouts of neuronal firing after sensitization was established. In migraine patients, fMRI assessment of BOLD signals showed that brush and heat stimulation at the skin of the dorsum of the hand produced larger BOLD responses in the posterior thalamus of subjects undergoing a migraine attack with extracephalic allodynia than the corresponding responses registered when the same patients were free of migraine and allodynia.

Interpretation

We propose that the spreading of multimodal allodynia and hyperalgesia beyond the locus of migraine headache is mediated by sensitized thalamic neurons that process nociceptive information from the cranial meninges together with sensory information from the skin of the scalp, face, body, and limbs. ANN NEUROL 2010
The Hubbard model extended by nearest‐neighbor Coulomb and exchange interaction on a cubic cluster – rigorous and exact results
Authors: Schumann R. , Zwicker D.
Published: April 2010

The Hubbard model on a cube was revisited and extended by both nearest‐neighbor Coulomb correlation W and nearest‐neighbor Heisenberg exchange J. The complete eigensystem was computed exactly for all electron occupancies and all model parameters ranging from minus infinity to plus infinity. For two electrons on the cluster the eigensystem is given in analytical form. For six electrons and infinite on‐site correlation U we determinded the groundstate and the groundstate energy of the pure Hubbard model analytically. For fixed electron numbers we found a multitude of ground state level crossings depending on the various model parameters. Furthermore the groundstates of the pure Hubbard model in dependence on a magnetic field h coupled to the spins are shown for the complete U‐h plane. The critical magnetic field, where the zero spin groundstate breaks down is given for four and six electrons. Suprisingly we found parameter regions, where the ground state spin does not depend monotonously on J in the extended model. For the cubic cluster gas, i.e. an ensemble of clusters coupled to an electron bath, we calculated the density n (μ, T, h) and the thermodynamical density of states from the grand potential. The ground states and the various spin‐spin correlation functions are studied for both attractive and repulsive values of the three interaction constants. We determined the various anomalous degeneration lines, where n (μ, T = 0, h = 0) shows steps higher than one, since in this parameter regions exotic phenomena as phase separation are to expect in extended models. For the cases where these lines end in triple points, i.e. groundstates of three different occupation numbers are degenerated, we give the related parameter values. Regarding the influence of the nn‐exchange and the nn‐Coulomb correlation onto the anomalous degeneration we find both lifting and inducing of degeneracies depending on the parameter values.
Different response to rituximab in tumor necrosis factor blocker–naive patients with active ankylosing spondylitis and in patients in whom tumor necrosis factor blockers have failed: A twenty‐four–week clinical trial
Authors: Song I.‐H. , Heldmann F. , Rudwaleit M. , Listing J. , Appel H. , Braun J. , Sieper J.
Published: April 2010

Objective

Histologic studies have shown B cell clusters in the subchondral bone marrow of the spine of patients with ankylosing spondylitis (AS). An immunotherapy targeting B cells in AS is therefore of interest. We undertook this study to examine the efficacy and safety of rituximab in patients with AS refractory to nonsteroidal antiinflammatory drugs in whom previous treatment with tumor necrosis factor α (TNFα) blockers either had not been tried or had failed.

Methods

In this phase II clinical trial, 1,000 mg rituximab was administered intravenously at baseline and at week 2 in 20 patients with active AS. Ten of these patients had never received TNF blockers, and treatment with TNF blockers had failed in the other 10 patients. The primary end point was a 20% improvement in disease activity at week 24 according to the criteria of the Assessment of SpondyloArthritis international Society (an ASAS20 response).

Results

Seventy‐five percent of the patients were male, 90% were HLA–B27 positive, their mean age was 39.7 years, and their mean disease duration was 16.8 years. Patients had active disease, defined as a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score ≥4. While there was no clear response at week 24 in the group in whom TNF blockers had failed (30% had achieved an ASAS20 response, 10% had achieved an ASAS40 response, none had achieved partial remission according to the ASAS criteria, and none had achieved 50% improvement on the BASDAI [a BASDAI50 response] beyond an expected placebo response), we observed a good improvement in the TNF blocker–naive group at week 24 (50% had achieved an ASAS20 response, 40% had achieved an ASAS40 response, 30% had achieved partial remission according to the ASAS criteria, and 50% had achieved a BASDAI50 response).

Conclusion

Although rituximab does not seem to be effective in patients with AS that does not respond to TNF blockers, it had significant efficacy in TNF blocker–naive patients. Therefore, further controlled trials with B cell–directed therapies should be performed in TNF blocker–naive AS patients in the future.
Targeted tumor necrosis factor receptor I preligand assembly domain improves skin lesions in MRL/lpr mice
Authors: Deng Guo‐Min , Liu Lena , Tsokos George C.
Published: April 2010

Objective

Skin disease is the second most common manifestation in patients with systemic lupus erythematosus (SLE). Tumor necrosis factor receptor (TNFR) preligand assembly domain (PLAD) has been found to block the effect of TNFα, and TNFRI PLAD (p60 PLAD) inhibits inflammatory arthritis. This study was undertaken to investigate whether TNFR PLAD limits inflammatory skin injury in a mouse model of SLE.

Methods

Female MRL/lpr mice received p60 PLAD (100 μg/mouse intraperitoneally), p80 PLAD (100 μg/mouse intraperitoneally), or phosphate buffered saline (100 μl/mouse intraperitoneally) 3 times a week for 26 weeks, starting at age 6 weeks.

Results

Immunohistochemistry studies demonstrated that TNFRI but not TNFRII was dominantly expressed in skin lesions in MRL/lpr mice. We found that TNFRI PLAD (p60 PLAD) but not TNFRII PLAD (p80 PLAD) protein significantly inhibited skin injury in the MRL/lpr mouse model of lupus. NF‐κB, monocyte chemotactic protein 1, and inducible nitric oxide synthase expression in skin lesions were significantly inhibited by p60 PLAD. Lupus serum–induced monocyte differentiation into dendritic cells was reduced by p60 PLAD, but p60 PLAD did not reduce IgG deposition in the skin or improve the progression of kidney damage in MRL/lpr mice.

Conclusion

Our results indicate that TNFRI is involved in the expression of skin injury in MRL/lpr mice with lupus and that p60 PLAD or similar biologics may be of clinical value if applied locally.
Selective functional inhibition of JAK‐3 is sufficient for efficacy in collagen‐induced arthritis in mice
Authors: Lin Tsung H. , Hegen Martin , Quadros Elizabeth , Nickerson‐Nutter Cheryl L. , Appell Kenneth C. , Cole Andrew G. , Shao Yuefei , Tam Steve , Ohlmeyer Michael , Wang Bojing , Goodwin Debra G. , Kimble Earl F. , Quintero Jorge , Gao Min , Symanowicz Peter , Wrocklage Christopher , Lussier Jennifer , Schelling Scott H. , Hewet Amha G. , Xuan Dejun , Krykbaev Rustem , Togias Jenny , Xu Xin , Harrison Richard , Mansour Tarek , Collins Mary , Clark James D. , Webb Maria L. , Seidl Katherine J.
Published: April 2010

Objective

All γ‐chain cytokines signal through JAK‐3 and JAK‐1 acting in tandem. We undertook this study to determine whether the JAK‐3 selective inhibitor WYE‐151650 would be sufficient to disrupt cytokine signaling and to ameliorate autoimmune disease pathology without inhibiting other pathways mediated by JAK‐1, JAK‐2, and Tyk‐2.

Methods

JAK‐3 kinase selective compounds were characterized by kinase assay and JAK‐3–dependent (interleukin‐2 [IL‐2]) and –independent (IL‐6, granulocyte–macrophage colony‐stimulating factor [GM‐CSF]) cell‐based assays measuring proliferation or STAT phosphorylation. In vivo, off‐target signaling was measured by IL‐22– and erythropoietin (EPO)–mediated models, while on‐target signaling was measured by IL‐2–mediated signaling. Efficacy of JAK‐3 inhibitors was determined using delayed‐type hypersensitivity (DTH) and collagen‐induced arthritis (CIA) models in mice.

Results

In vitro, WYE‐151650 potently suppressed IL‐2–induced STAT‐5 phosphorylation and cell proliferation, while exhibiting 10–29‐fold less activity against JAK‐3–independent IL‐6– or GM‐CSF–induced STAT phosphorylation. Ex vivo, WYE‐151650 suppressed IL‐2–induced STAT phosphorylation, but not IL‐6–induced STAT phosphorylation, as measured in whole blood. In vivo, WYE‐151650 inhibited JAK‐3–mediated IL‐2–induced interferon‐γ production and decreased the natural killer cell population in mice, while not affecting IL‐22–induced serum amyloid A production or EPO‐induced reticulocytosis. WYE‐151650 was efficacious in mouse DTH and CIA models.

Conclusion

In vitro, ex vivo, and in vivo assays demonstrate that WYE‐151650 is efficacious in mouse CIA despite JAK‐3 selectivity. These data question the need to broadly inhibit JAK‐1–, JAK‐2–, or Tyk‐2–dependent cytokine pathways for efficacy.
Microwave‐Hydrothermal Preparation and Visible‐Light Photoactivity of Plasmonic Photocatalyst Ag‐TiO2 Nanocomposite Hollow Spheres
Authors: Xiang Quanjun , Yu Jiaguo , Cheng Bei , Ong H. C.
Published: April 2010

Visible‐light‐driven plasmonic photocatalyst Ag‐TiO2 nanocomposite hollow spheres are prepared by a template‐free chemically‐induced self‐transformation strategy under microwave‐hydrothermal conditions, followed by a photochemical reduction process under xenon lamp irradiation. The prepared samples are characterized by using scanning electron microscopy, transmission electron microscopy, X‐ray diffraction, N2 adsorption‐desorption isotherms, X‐ray photoelectron spectroscopy, UV/Vis and Raman spectroscopy. Production of ⋅OH radicals on the surface of visible‐light illuminated TiO2 was detected by using a photoluminescence method with terephthalic acid as the probe molecule. The photocatalytic activity of as‐prepared samples was evaluated by photocatalytic decolorization of Rhodamine B (RhB) aqueous solution at ambient temperature under visible‐light irradiation. The results show that the surface plasmon absorption band of the silver nanoparticles supported on the TiO2 hollow spheres was red shifted, and a strong surface enhanced Raman scattering effect for the Ag‐TiO2 nanocomposite sample was observed. The prepared nanocomposite hollow spheres exhibits a highly visible‐light photocatalytic activity for photocatalytic degradation of RhB in water, and their photocatalytic activity is higher than that of pure TiO2 and commercial Degussa P25 (P25) powders. Especially, the as‐prepared Ag‐TiO2 nanocomposite hollow spheres at the nominal atomic ratio of silver to titanium (R) of 2 showed the highest photocatalytic activity, which exceeds that of P25 by a factor of more than 2.
Transition‐Metal‐Catalyzed Cycloadditions for the Synthesis of Eight‐Membered Carbocycles
Authors: Yu Zhi‐Xiang , Wang Yi , Wang Yuanyuan
Published: April 2010

Eight‐membered carbocycles are found in a wide variety of natural products that exhibit a broad range of biological and medicinal activities (cf. the most potent anticancer drug, taxol). However, the synthesis of eight‐membered carbocycles is quite challenging as traditional approaches are met with entropic and enthalpic penalties in the ring‐forming transition states. These negative effects can be totally or partially avoided with the implementation of transition‐metal‐catalyzed/mediated cycloadditions. In this Focus Review, examples of elegant and efficient metal‐catalyzed and some metal‐mediated cycloadditions (including Ni‐ catalyzed [4+4] and Rh‐catalyzed [4+2+2] and [5+2+1] reactions) are presented to illustrate this. Application of these cycloaddition reactions in total synthesis is also presented to show the significance of these reactions in addressing challenges in natural product synthesis.
Quadruplexes of human telomere DNA analogs designed to contain G:A:G:A, G:G:A:A, and A:A:A:A tetrads
Authors: Sagi Janos , Renčiuk Daniel , Tomaško Martin , Vorlíčková Michaela
Published: April 2010

Replacement of two to four guanines by adenines in the human telomere DNA repeat dG3(TTAG3)3 did not hinder the formation of quadruplexes if the substitutions took place in the terminal tetrad bridged by the diagonal loop of the intramolecular antiparallel three‐tetrad scaffold, as proved by CD and PAGE in both Na+ and K+ solutions. Thermodynamic data showed that, in Na+ solution, the dG3(TTAG3)3 quadruplex was destabilized, the least by the two G:A:G:A tetrads, the most by the G:G:A:A tetrad in which the adenosines replaced syn‐guanosines. In physiological K+ solution, the highest destabilization was caused by the 4A tetrad. In K+, only the unmodified dG3(TTAG3)3 quadruplex rearranged into a K+‐dependent quadruplex form, none of the multiple adenine‐modified structures did so. This may imply biological consequences for nonrepaired A‐for‐G mutations. © 2010 Wiley Periodicals, Inc. Biopolymers 93: 880–886, 2010.
Stressful life events and suicidal behaviour in countries with different development levels: Nicaragua, El Salvador, Chile and Spain
Authors: Vázquez José Juan , Panadero Sonia , Rincón Paulina Paz
Published: April 2010

This paper presents a study conducted on 709 Latin American undergraduates from four countries with different development levels (Nicaragua, El Salvador, Chile and Spain). The intention of this paper is to value the differences in the number and characteristics of stressful life events (SLE) suffered by the participants. Another purpose is to confirm the relation between SLE and suicidal conduct in Spanish cultural contexts, through the study of a multicultural sample of Spanish‐speaking university students, and finally, to isolate the SLE that allow predicting a later suicidal conduct to a greatest extent. The information was collected by means of a self‐applied questionnaire. The results indicate a greater presence of SLE among those who live in countries with lower development levels and among those who have attempted committing suicide. It is observed that the fact of having suffered certain SLE—physical or sexual mistreatment, excessive alcohol or drug consumption and having left home during childhood or adolescence—aid in the prediction of later suicidal conducts in the studied samples. Copyright © 2010 John Wiley & Sons, Ltd.
Domestic violence and mental health in a Dutch community sample: The adverse role of loneliness
Authors: Kunst Maarten , Bogaerts Stefan , Winkel Frans Willem
Published: April 2010

The present study explored whether the adverse mental health consequences of domestic violence victimization vary by type of loneliness (i.e., emotional and social loneliness). Participants were drawn from the Dutch city of Rotterdam (N = 7072). Domestic violence victimization, emotional loneliness and social loneliness were associated with self‐reported mental health. In addition, interaction effects were observed between domestic violence victimization and each type of loneliness. Implications for policy practice as well as strengths and limitations of the study were discussed. Copyright © 2010 John Wiley & Sons, Ltd.
An Unusual Thioesterase Promotes Isochromanone Ring Formation in Ajudazol Biosynthesis
Authors: Buntin Kathrin , Weissman Kira J. , Müller Rolf
Published: April 2010

The ajudazols are antifungal secondary metabolites produced by a hybrid polyketide synthase (PKS)‐nonribosomal peptide synthetase (NRPS) multienzyme “assembly line” in the myxobacterium Chondromyces crocatus Cm c5. The most striking structural feature of these compounds is an isochromanone ring system; such an aromatic moiety is only known from two other complex polyketides, the electron transport inhibitor stigmatellin and the polyether lasalocid. The cyclization and aromatization reactions in the stigmatellin pathway are presumed to be catalyzed by a cyclase domain located at the end of the PKS, while the origin of the lasalocid benzenoid ring remains obscure. Notably, the ajudazol biosynthetic machinery does not incorporate a terminal cyclase, but instead a variant thioesterase (TE) domain. Here we present detailed phylogenetic and sequence analysis, coupled with experiments both in vitro and in vivo, that suggest that this TE promotes formation of the isochromanone ring, a novel reaction for this type of domain. As the ajudazol TE has homologues in several other secondary‐metabolite pathways, these results are likely to be generalizable.
Transcatheter occlusion of an azygous vein aneurysm
Authors: Weber Howard S.
Published: April 2010

We describe the use of multiple Amplatzer vascular plugs which were intentionally placed so as to isolate a large azygous vein aneurysm with intraluminal thrombosis, which had resulted in a previous pulmonary embolus. This technique avoided the need for an invasive thoracotomy and aneurysm resection or attempting to directly fill the large aneurysm with numerous and various embolization devices. © 2010 Wiley‐Liss, Inc.
The index of microcirculatory resistance (IMR) in takotsubo cardiomyopathy
Authors: Daniels David V. , Fearon William F.
Published: April 2010

We report a patient who presents with acute chest pain and positive cardiac enzymes clinically consistent with an acute coronary syndrome (ACS). Coronary angiography revealed normal epicardial arteries and the left ventriculogram was notable for apical ballooning. This was strongly suggestive of takotsubo cardiomyopathy. Pressure wire measurements of Fractional flow reserve (FFR) and IMR demonstrated a normal FFR, but significant microcirculatory dysfunction. This is the first such case that documents this abnormality invasively using the IMR, which unlike CFR is specific for the microcirculation and reproducible through a range of hemodynamic states. © 2010 Wiley‐Liss, Inc.