bluuebunny/crossref_metadata_2025 huggingface dataset:
BCL-2 Family Proteins: Critical Checkpoints of Apoptotic Cell Death
Authors: Danial Nika N.
Published: December 2007

Apoptosis is a morphologically distinct form of programmed cell death essential for normal development and tissue homeostasis. Aberrant regulation of this pathway is linked to multiple human diseases, including cancer, autoimmunity, neurodegenerative disorders, and diabetes. The BCL-2 family of proteins constitutes a critical control point in apoptosis residing immediately upstream of irreversible cellular damage, where family members control the release of apoptogenic factors from mitochondria. The cardinal member of this family, BCL-2, was originally discovered as the defining oncogene in follicular lymphomas, located at one reciprocal breakpoint of the t(14;18) (q32;q21) chromosomal translocation. Since this original discovery, remarkable efforts marshaled by many investigators around the world have advanced our knowledge of the basic biology, molecular mechanisms, and therapeutic targets in the apoptotic pathway. This review highlights findings from many laboratories that have helped uncover some of the critical control points in apoptosis. The emerging picture is that of an intricate cellular machinery orchestrated by tightly regulated molecular interactions and conformational changes within BCL-2 family proteins that ultimately govern the cellular commitment to apoptotic death.
EWSR1-CREB1 and EWSR1-ATF1 Fusion Genes in Angiomatoid Fibrous Histiocytoma
Authors: Rossi Sabrina , Szuhai Kàroly , Ijszenga Marije , Tanke Hans J. , Zanatta Lucia , Sciot Raf , Fletcher Christopher D.M. , Dei Tos Angelo P. , Hogendoorn Pancras C.W.
Published: December 2007

Purpose: Angiomatoid fibrous histiocytoma (AFH) is a low-grade mesenchymal neoplasm which usually occurs in children and adolescents. Either FUS-ATF1 or EWSR1-ATF1 have been detected in the few cases published, pointing to the interchangeable role of FUS and EWSR1 in this entity. EWSR1-ATF1 also represents the most frequent genetic alteration in clear cell sarcoma, suggesting the existence of a molecular homology between these two histotypes. We investigated the presence of EWSR1-CREB1, recently found in gastrointestinal clear cell sarcoma, and FUS-CREB1, as well as the already reported FUS-ATF1 and EWSR1-ATF1 in a series of AFH.

Experimental Design: Fourteen cases were analyzed by fluorescence in situ hybridization (FISH) on paraffin-embedded tissue sections, using a commercial EWSR1 probe and custom-designed probes for FUS, ATF1, and CREB1. In two cases, four-color FISH was also done. Reverse transcription-PCR for the four hypothetical fusion genes was done in one case, for which frozen material was available.

Results: Thirteen cases showed rearrangements of both EWSR1 and CREB1, whereas one case showed the rearrangement of both EWSR1 and ATF1. Four-color FISH confirmed the results in two selected cases. Reverse transcription-PCR showed EWSR1-CREB1 transcript in the case analyzed.

Conclusion: We identified the presence of either EWSR1-CREB1 or EWSR1-ATF1 in all the cases, strengthening the concept of chromosomal promiscuity between AFH and clear cell sarcoma. Either the occurrence of a second unknown tumor-specific molecular event or, perhaps more likely, divergent differentiation programs of the putatively distinct precursor cells of AFH and clear cell sarcoma might be invoked in order to explain the two different phenotypes.
From the Field: A Proposal for Educating Leaders for Social Justice
Authors: McKenzie Kathryn Bell , Christman Dana E. , Hernandez Frank , Fierro Elsy , Capper Colleen A. , Dantley Michael , González María Luisa , Cambron-McCabe Nelda , Scheurich James Joseph
Published: December 2007

Purpose: The purpose of this article is to suggest the structure and content of an educational leadership program whose aim is to prepare principals for social justice work. Research Design: The authors have conceptualized foundational components for a comprehensive principalship program focused on social justice. They assert that educational leaders for social justice must have three goals at the forefront of their efforts: (a) They must raise the academic achievement of all the students in their school, that is, high test scores do matter; (b) they must prepare their students to live as critical citizens in society; and (c) both of these goals can only be achieved when leaders assign students to inclusive, heterogeneous classrooms that provide all students access to a rich and engaging curriculum. The components addressed for this social justice—oriented principalship preparation program include (a) how students should be selected for such a program and (b) an outline of the knowledge and content for educating social justice leaders. The importance of induction/praxis after students graduate from these programs is discussed.

Conclusions: The aim of this article is to provoke a discussion in the field and spark faculty to engage in ongoing conversations and thinking about their own programs and to imagine new avenues for future research in this area. Faculty also can use these suggestions as a guide to assess their efforts and to bolster program quality, sensitive to the unique needs and schooling contexts of their particular students.
Europeanization, Uploading and Downloading
Authors: Connolly John
Published: December 2007

Avian influenza (AI) has called for transnational policy making by member state governments and the EU as outbreaks of the disease have spread across state boundaries. The focus of this article is on the relationship between the UK and EU surrounding the AI case study from 2005 to early 2007. The analysis is informed by interviews conducted with officials based in the Department for the Environment, Food and Rural Affairs (Defra) who have been involved in projecting or `uploading' national policy preferences to the European Commission and, at the same time, accommodating or `downloading' the rules and regulations that have emanated mainly from the Standing Committee for Food Chain and Animal Health (SCFCAH) of the Commission. The article, therefore, adopts a dynamic view of Europeanization processes in order to analyse transnational policy making for AI outbreaks. The article shows that dynamic Europeanization processes are effective in conceptualizing and explaining transnational policy making for AI across the UK and EU levels.
Changing UK Governance under Devolution
Authors: Parry Richard
Published: December 2007

The 2007 elections in Northern Ireland, Scotland and Wales resulted in nationalist ministers entering the devolved governments and holding out the prospect of new patterns of governance. The article examines some early initiatives, including moves towards a separate Scottish Civil Service, greater integration of the Scottish Executive, a pro-welfare state coalition in Wales, a Northern Ireland Executive reappraising moves to public sector reform under direct rule, and pressure for more formalized mechanisms of intergovernmental relations within the UK. As nationalist parties lack the political majority to take forward their constitutional aspirations, their main contribution to governance may come through developing an alternative centre-left perspective on traditional UK patterns.
Using Anonymized Reflection To Teach Ethics: a Pilot Study
Authors: Kyle Gaye
Published: December 2007

Anonymized reflection was employed as an innovative way of teaching ethics in order to enhance students' ability in ethical decision making during a `Care of the Dying Patient and Family' module. Both qualitative and quantitative data were collected from the first two student cohorts who experienced anonymized reflection ( n = 24). The themes identified were the richness and relevance of scenarios, small-group work and a team approach to teaching. Students indicated that they preferred this style of teaching. This finding was verified by a postal questionnaire conducted four months later. The conclusions drawn from this study suggest that using anonymized reflection is an effective method for teaching ethics to nurses and indicates that learning about ethical issues in this way reduces uncertainties.
Three Nursing Home Residents Speak About Meaning At the End of Life
Authors: Dwyer Lise-Lotte , Nordenfelt Lennart , Ternestedt Britt-Marie
Published: December 2007

This article provides a deeper understanding of how meaning can be created in everyday life at a nursing home. It is based on a primary study concerning dignity involving 12 older people living in two nursing homes in Sweden. A secondary analysis was carried out on data obtained from three of the primary participants interviewed over a period of time (18—24 months), with a total of 12 interviews carried out using an inductive hermeneutic approach. The study reveals that sources of meaning were created by having a sense of: physical capability, cognitive capability, being needed, and belonging. Meaning was created through inner dialogue, communication and relationships with others. A second finding is that the experience of meaning can sometimes be hard to realize.
Peer Sexual Harassment
Authors: Martin Jennifer L.
Published: December 2007

This exploratory intervention study examines the effectiveness of a single-sex women's studies course in reducing sexual harassment in an at-risk high school. It was hypothesized that the young women's loci of control would become more internal as a result of the course and participants would feel they had more control over their lives. Findings indicate that participants' knowledge of sexual harassment gained from the intervention had been retained and reports of sexual harassment increased. Administrative referrals for sexual harassment within the school were reduced by one third during the semester following the intervention. Participants' perceptions of their levels of internality increased over time.
Pathways to Building Leadership Capacity
Authors: Slater Lorraine
Published: December 2007

Within the complex working of today's schools, as principals share the lead and the load, the success of their performance will be determined by their ability to inspire a culture of empowerment by acting as `hero-makers' rather than heroes. Drawing on the resources of others is essential for the site-based breakthroughs or change in complex school systems and in turn builds human capacity and self-knowledge. In order to develop human potential, the leader needs to know people well, look for strengths in individuals, and build upon them. Effective communication is instrumental in establishing collaborative relationships and is a key aspect of building leadership capacity in a school. These relationships provide the framework within which we come to understand and value each other's experiences, interests, and dreams. In this article, I will discuss the findings of a study that describe how principals used communication strategies and skills to foster the empowerment of other stakeholders within the context of collaborative initiatives. The findings from this qualitative focus group study involving principals, parents and teachers demonstrate that leaders can use several communication techniques to encourage shared leadership and thereby to build human and organizational capacity.
Secondary School Leadership Practice in Botswana
Authors: Pheko Bolelang
Published: December 2007

This article analyses the views of selected headteachers on the impact of the 10-year basic education policy on the leadership skills of secondary school headteachers in Botswana. Research literature on school leadership and management in Botswana is sparse. Despite this, demands for effective leadership in schools have continued as the education system changes. In 1996, the Botswana Government started to implement a 10-year basic education programme, which rapidly increased student numbers at both community junior and senior secondary schools and building projects for school expansion became the order of the day. Secondary school headteachers have to manage these changes. A central focus of this article is their perceptions of the practice used to appoint them, leadership skills required for the post, their leadership training, and how training for leadership can be improved to meet the educational changes. Using results of the interview data collected from eight selected secondary school headteachers, this article exposes the limitations of the practice and procedures that are used in appointing headteachers to school leadership position and the established procedures intended to develop a skilled leadership force in secondary education to ensure quality education. The article highlights the need for Botswana to establish a leadership training policy to guide the training of headteachers and ensure that schools become effective.
Sox18 and Sox7 play redundant roles in vascular development
Authors: Cermenati Solei , Moleri Silvia , Cimbro Simona , Corti Paola , Del Giacco Luca , Amodeo Roberta , Dejana Elisabetta , Koopman Peter , Cotelli Franco , Beltrame Monica
Published: December 2007

Mutations in SOX18 cause the human hypotrichosis-lymphedema-telangiectasia (HLT) syndrome. Their murine counterparts are the spontaneous ragged mutants, showing combined defects in hair follicle, blood vessel, and lymphatic vessel development. Mice null for Sox18 display only mild coat defects, suggesting a dominant-negative effect of Sox18/ragged mutations and functional redundancy between Sox18 and other Sox-F proteins. We addressed this point in zebrafish. The zebrafish homologs of Sox18 and of Sox7 are expressed in angioblasts and in the endothelial component of nascent blood vessels in embryos. Knockdown of either gene, using moderate doses of specific morpholinos, had minimal effects on vessels. In contrast, simultaneous knockdown of both genes resulted in multiple fusions between the major axial vessels. With combined use of transgenic lines and molecular markers, we could show that endothelial cells are specified, but fail to acquire a correct arteriovenous identity. Venous endothelial cell differentiation was more severely affected than arterial. Thus, sox7 and sox18 play redundant but collectively essential roles in the establishment of proper arteriovenous identity in zebrafish. Our data suggest that a defect in arteriovenous identity could be responsible for the formation of telangiectases in patients with HLT.
SWAP-70 deficiency causes high-affinity plasma cell generation despite impaired germinal center formation
Authors: Quemeneur Laurence , Angeli Veronique , Chopin Michael , Jessberger Rolf
Published: December 2007

Germinal centers (GCs) are lymphoid tissue structures central to the generation of long-lived, high-affinity, antibody-forming B cells. However, induction, maintenance, and regulation of GCs are not sufficiently understood. The F-actin–binding, Rac-interacting protein SWAP-70 is strongly expressed in activated B cells like those in B follicles. Recent work suggests that SWAP-70 is involved in B-cell activation, migration, and homing. Therefore, we investigated the role of SWAP-70 in the T-dependent immune response, in GC formation, and in differentiation into plasma and memory B cells. Compared with wt, sheep red blood cell (SRBC)–, or NP-KLH–immunized SWAP-70−/− mice have strongly reduced numbers of GCs and GC-specific B cells. However, SWAP-70−/− NP-specific B cells accumulate outside of the B follicles, and SWAP-70−/− mice show more plasma cells in the red pulp and in the bone marrow, and increased NP-specific Ig and antibody-forming B cells. Yet the memory response is impaired. Thus, SWAP-70 deficiency uncouples GC formation from T-dependent antibody and long-lived plasma cell production and causes extrafollicular generation of high-affinity plasma cells, but does not adequately support the memory response.
The specificity of JAK3 kinase inhibitors
Authors: Changelian Paul S. , Moshinsky Deborah , Kuhn Cyrille F. , Flanagan Mark E. , Munchhof Michael J. , Harris Thomas M. , Whipple David A. , Doty Jonathan L. , Sun Jianmin , Kent Craig R. , Magnuson Kelly S. , Perregaux David G. , Sawyer Perry S. , Kudlacz Elizabeth M.
Published: December 2007

PF-956980 is a selective inhibitor of JAK3, related in structure to CP-690550, a compound being evaluated in clinical trials for rheumatoid arthritis and prevention of allograft rejection. PF-956980 has been evaluated against a panel of 30 kinases, and found to have nanomolar potency against only JAK3. Cellular and whole blood activity of this compound parallels its potency and selectivity in enzyme assays. It was effective in vivo at inhibiting the delayed type hypersensivity reaction in mice. We compared 2 commercially available JAK3 inhibitors (WHI-P131 and WHI-P154) in the same panel of biochemical and cellular assays and found them to be neither potent nor selective for JAK3. Both were found to be nanomolar inhibitors of the EGF receptor family of kinases. As these compounds have been used in numerous publications in the transplant and autoimmune disease literature, their specificity should be considered when interpreting these results.
Lung carcinomas with a basaloid pattern: a study of 90 cases focusing on their poor prognosis
Authors: Moro-Sibilot D. , Lantuejoul S. , Diab S. , Moulai N. , Aubert A. , Timsit J. F. , Brambilla C. , Brichon P. Y. , Brambilla E.
Published: December 2007

Lung carcinoma with a basaloid pattern (BC) is classified as either a basaloid variant of squamous cell carcinoma (SCC) or as variant of large cell carcinoma (LCC) depending on the presence of a squamous component. In a previous study of 37 cases, the present authors showed that BC presented with a shorter median and overall survival.

In order to confirm its clinical significance in a larger series, 90 BC, including 46 basaloid variants of LCC and 44 basaloid variants of SCC, were compared with 1,328 other nonsmall cell lung carcinoma (NSCLC) with regard to clinical features and survival.

The survival of basaloid variants of LCC and SCC was comparable. Median and overall survival were significantly lower for BC than for NSCLC in stage I–II patients, with a median survival of 29 and 49 months, respectively, and 5-yr survival rates of 27 and 44% for BC and NSCLC. When disease-specific survival was considered, BC had a shorter survival than both NSCLC and SCC.

Basaloid pattern confers a poor prognosis in nonsmall cell lung carcinoma, especially in stage I–II patients, suggesting that lung carcinoma with a basaloid pattern is not only a variant of squamous cell carcinoma or large cell carcinoma, but is a unique entity with a significantly poor prognosis.
Effect of growth hormone therapy on nitric oxide formation in cystic fibrosis patients
Authors: Grasemann C. , Ratjen F. , Schnabel D. , Reutershahn E. , Vester U. , Grasemann H.
Published: December 2007

Airway nitric oxide production is decreased in cystic fibrosis. As growth hormone therapy has been shown to increase nitric oxide production in growth hormone-deficient patients, it may also affect nitric oxide production in patients with cystic fibrosis. The objective of the present study was to investigate the effect of growth hormone therapy on systemic and airway nitric oxide formation in patients with cystic fibrosis.

Nitric oxide metabolites in serum and urine, amino acid concentrations in serum and sputum, as well as exhaled nitric oxide, were measured in children with cystic fibrosis before, during and after 1 yr of treatment with human growth hormone.

Nitric oxide metabolite concentrations increased significantly in serum and urine during the treatment period. Serum amino acid concentrations (includingl-arginine, the substrate for nitric oxide synthases) also increased during treatment. The systemic bioavailability ofl-arginine for nitric oxide synthases, expressed as ratio ofl-arginine/l-ornithine+lysine, remained unchanged. In contrast,l-arginine concentrations in sputum decreased significantly during growth hormone treatment, as did exhaled nitric oxide levels.

Treatment with growth hormone in children with cystic fibrosis decreases exhaled nitric oxide by reducing the concentration ofl-arginine in the airways.
A small-molecule compound targeting CCR5 and CXCR3 prevents airway hyperresponsiveness and inflammation
Authors: Suzaki Y. , Hamada K. , Nomi T. , Ito T. , Sho M. , Kai Y. , Nakajima Y. , Kimura H.
Published: December 2007

Asthma is associated with increased numbers of T-cells in the lung. CC chemokine receptor (CCR)5 and CXC chemokine receptor (CXCR)3 have been reported to play important roles in the lung T-cell homing pathway, and may be potential targets for asthma therapy. The aim of the present study was to investigate the role of CCR5 and CXCR3 in allergen-induced acute asthma and to determine whether a novel small-molecule compound, TAK-779, targeting CCR5 and CXCR3 can attenuate allergic airway responses.

Mice were sensitised with ovalbumin (OVA). mRNA expression of chemokine receptors in the lung were measured after the challenge with either aerosolised phosphate-buffered saline or OVA. OVA-sensitised mice were also treated with TAK-779. Respiratory function was measured, bronchoalveolar lavage was performed, and blood and lung samples were obtained.

OVA challenge increased CCR3, CCR5 and CXCR3 expression in the lung. Treatment with TAK-779 significantly attenuated altered respiratory function and pulmonary allergic inflammation. The beneficial effect was associated with reduced expression of CCR5 and CXCR3 in the lung.

These data demonstrate that blockade of CC chemokine receptor 5 and CXC chemokine receptor 3 using TAK-779, a synthetic nonpeptide compound, can prevent the development of asthma features in a mouse model. Thus, CC chemokine receptor 5 and CXC chemokine receptor 3 may be potential targets for asthma therapy.
Troponin I and risk stratification of patients with acute nonmassive pulmonary embolism
Authors: Jiménez D. , Díaz G. , Molina J. , Martí D. , Del Rey J. , García-Rull S. , Escobar C. , Vidal R. , Sueiro A. , Yusen R. D.
Published: December 2007

The assessment of risk and appropriate treatment of patients with acute pulmonary embolism (PE) remains a challenge.

The prognostic performance of cardiac troponin I (cTnI) in predicting 30-day all-cause mortality was prospectively assessed in consecutive haemodynamically stable patients with PE.

The present study included 318 haemodynamically stable patients with PE. During the 30-day study period, 23 (7%) patients died. cTnI was elevated (≥0.1 ng·mL−1) in 102 (32%) patients. An age >65 yrs, systolic blood pressure <120 mmHg and severity of illness assessed using the PE severity index (PESI) were significantly associated with an increased risk for mortality, but no significant association was found between elevation of cTnI and 30-day mortality in a logistic regression analysis. When only fatal PE was considered, multivariate analysis showed that severity of illness using the PESI and an elevated cTnI (odds ratio 3.7, 95% confidence interval (CI) 1.1–12.8) were associated with a significant increase in the risk for death. The negative predictive value (95% CI) of a negative cTnI for mortality was 93 (90–97)%.

In conclusion, in haemodynamically stable patients with acute pulmonary embolism, cardiac troponin I was not an independent predictor of 30-day all-cause mortality, although it did predict fatal pulmonary embolism.
Spontaneous immune responses against glioma-associated antigens in a long term survivor with malignant glioma
Authors: Ueda Ryo , Low Keri L , Zhu Xinmei , Fujita Mitsugu , Sasaki Kotaro , Whiteside Theresa L , Butterfield Lisa H , Okada Hideho
Published: December 2007

Background

In patients with high grade glioma, little is known regarding existence of naturally occurring adaptive T cell reactivity against glioma-associated antigens (GAAs). In this report, we characterized GAA-specific CD8+ T cells and innate immune cells in a patient who has survived with anaplastic astrocytoma (AA) for over 12 years without recurrence.

Methods

Peripheral blood mononuclear cells (PBMCs) derived from the long term survivor with AA were evaluated for the frequency, cytotoxic T lymphocyte (CTL) activity and differentiation status of CD8+ cells recognizing GAA-derived epitopes as well as relative numbers of other immune cell subsets. This patient's AA tissue was evaluated for expression of two GAAs EphA2 and interleukin-13 receptor α2 subunit (IL-13Rα2) by immunohistochemistry.

Results

The patient's tumor expressed both EphA2 and IL-13Rα2, and in vitro stimulated PBMC demonstrated superior EphA2883–891 and IL-13Rα2345–353-specific CTL reactivity compared to PBMC samples from two other patients with progressing malignant glioma. Unstimulated EphA2883–891-reactive CD8+ T cells contained high numbers of CD45RA-/CCR7- late effector and CD45RA-/CCR7+ central memory cells. Among other leukocyte subsets, elevated numbers of NK-T cells were found.

Conclusion

To our knowledge, the current study is one of the first demonstrating the presence of antigen-experienced, GAA-reactive CD8+ T cells in a patient who has survived with AA for over 12 years without recurrence. Further studies are warranted to determine whether the status of GAA-reactive CD8+ T cells dictates survival of patients and/or response to therapeutic vaccines.
Insm1 (IA-1) is a crucial component of the transcriptional network that controls differentiation of the sympatho-adrenal lineage
Authors: Wildner Hendrik , Gierl Mathias S. , Strehle Michael , Pla Patrick , Birchmeier Carmen
Published: December 2007

Insm1 (IA-1) encodes a Zn-finger factor that is expressed in the developing nervous system. We demonstrate here that the development of the sympatho-adrenal lineage is severely impaired in Insm1 mutant mice. Differentiation of sympatho-adrenal precursors, as assessed by the expression of neuronal subtype-specific genes such as Th and Dbh, is delayed in a pronounced manner, which is accompanied by a reduced proliferation. Sympathetic neurons eventually overcome the differentiation blockade and mature correctly, but sympathetic ganglia remain small. By contrast, terminal differentiation of adrenal chromaffin cells does not occur. The transcription factors Mash1 (Ascl1), Phox2a, Gata3 and Hand2(previously dHand) control the differentiation of sympatho-adrenal precursor cells, and their deregulated expression in Insm1 mutant mice demonstrates that Insm1 acts in the transcriptional network that controls differentiation of this lineage. Pronounced similarities between Mash1 and Insm1 phenotypes are apparent, which suggests that Insm1 might mediate aspects of Mash1 function in the subtype-specific differentiation of sympatho-adrenal precursors. Noradrenaline is the major catecholamine produced by developing sympatho-adrenal cells and is required for fetal survival. We demonstrate that the fetal lethality of Insm1 mutant mice is caused by catecholamine deficiency, which highlights the importance of Insm1 in the development of the sympatho-adrenal lineage.
Lgl and its phosphorylation by aPKC regulate oocyte polarity formation inDrosophila
Authors: Tian Ai-Guo , Deng Wu-Min
Published: December 2007

Specification of the anteroposterior (AP) axis in Drosophilaoocytes requires proper organization of the microtubule and actin cytoskeleton. The establishment and regulation of cytoskeletal polarity remain poorly understood, however. Here, we show important roles for the tumor suppressor Lethal (2) giant larvae (Lgl) and atypical protein kinase C (aPKC)in regulating microtubule polarity and setting up the AP axis of the oocyte. Lgl in the germline cells regulates the localization of axis-specifying morphogens. aPKC phosphorylation of Lgl restricts Lgl activity to the oocyte posterior, thereby dividing the cortex into different domains along the AP axis. Active Lgl promotes the formation of actin-rich projections at the oocyte cortex and the posterior enrichment of the serine/threonine kinase Par-1, a key step for oocyte polarization. Our studies suggest that Lgl and its phosphorylation by aPKC may form a conserved regulatory circuitry in polarization of various cell types.
Research Note—A Theoretical Investigation of the Effects of Similarity on Brand Choice Using the Elimination-by-Tree Model
Authors: Won Eugene J. S.
Published: December 2007

IIA (independence of irrelevant alternatives) axiom states that the ratio of choice probabilities of any two brands will depend only on the utilities of the brands. However, even if the utilities of brands are assumed to be fixed, their choice probabilities will be affected by the similarity between them. This study and several other previous studies show that a more preferred (higher utility) brand benefits more in a high similarity situation than a less preferred (lower utility) brand, which is called the asymmetric similarity effect or simply the asymmetric effect in this study. This study expands on the asymmetric effect that has been reported by many previous empirical studies and implied in choice modeling literature, by giving it an explicit mathematical formulation based on the analysis of the elimination-by-tree (EBT) model (Tversky and Sattath 1979). This study also provides an integrative theoretical summary showing how the asymmetric effect is related to the similarity effect, dominance effect, and IIA condition.
The Value of Quality
Authors: Tellis Gerard J. , Johnson Joseph
Published: December 2007

Product quality is probably undervalued by firms because there is little consensus about appropriate measures and methods to research quality. We suggest that published ratings of a product's quality are a valid source of quality information with important strategic and financial impact. We test this thesis by an event analysis of abnormal returns to stock prices of firms whose new products are evaluated in The Wall Street Journal. Quality has a strong immediate effect on abnormal returns, which is substantially higher than that for other marketing events assessed in prior studies. Moreover, there are some important asymmetries in the effect. We discuss the research, managerial, investing, and policy implications.
‘Social Balance’ and New Town Organisations
Authors: Wirz Hans
Published: December 2007

The legislative foundation for the building of new towns in Britain was laid in October 1945, when the New Towns Committee was appointed under the chairmanship of Lord Reith. Its terms of reference were:

‘To consider the general questions of the establishment, development, organisation and administration that will arise in the promotion of New Towns … and to suggest guiding principles on which such towns should be established and developed as self-contained and balanced communities for work and living.’

Some of the most important intentions in the creation of the new towns are expressed in the goal that they should be self-contained and balanced communities for work and living. The idea of self-containment was seen as being fairly straightforward. The new towns would not simply contain residential areas, but were to be designed to encompass, as Thomas put it, within their boundaries, ‘all of the requirements for day-to-day living.’ As part of those requirements, the Reith committee counted social organisations through which it would be possible for a newcomer to ‘put down roots in his community’.
Information Needs and Planning in Social Services Department
Authors: Leigh Andrew , White Michael
Published: December 2007

In late 1972 Social Service Departments were formally requested by the Department of Health and Social Security to prepare development plans covering the next ten years. Ten years earlier local health and welfare authorities had been asked to do the same exercise and the results appeared in April, 1963, and were subsequently revised twice. After 1965 demands for ten year planning ceased although shorter-term three-year capital programme forecasting did continue. With the amalgamations of welfare, mental health and children’s departments under the Seebohm re-organisations in 1971, ten-year planning has come back into fashion, this time in a rather more detailed form, especially in respect of manpower forecasting. Criteria, admittedly very unsophisticated, were provided by the DHSS and suggestions on the organisation of the planning task were issued by the Social Services Research Group. Though some authorities, notably those well advanced with corporate planning models seem to have found the creation of ten year plans relatively painless, others found it much more difficult and this was doubtless reflected in the fact that around half of the plans missed the DHSS delivery deadline set for 28 February, 1973.
The British Urban Programme
Authors: Holman Robert , Hamilton Lynda
Published: December 2007

Although it is now over four years since the British urban programme was initiated, available information on its origins, the details of its implementation and the extent to which it has been successful continues to be severely limited. The literature on this topic is restricted to a few critical articles which, in the main, have focussed on details of the implementation of the programme, while systematic research in this area is conspicuous for its absence. This paper provides an analysis of the information that is currently available drawing upon such sources as relevant government circulars and statements, interviews with civil servants, a number of written contributions from voluntary bodies involved in the programme and a few but valuable contacts with local government councillors and officials. Considerable insight has also been gained from the practical experience of one of the writers who participated in the process of making application for urban programme grants for two projects. On this basis, it has been possible to present an outline of the programme’s origins, the organisation and proedures established to administer it and some of the changes which have apparently taken place since its initiation.
The Comparative Study of Local Government Organisation: 1972–6
Authors: Greenwood Royston , Hinings C. R.
Published: December 2007

Unless the intentions of the Conservative government are thwarted, existing local authorities in England and Wales, other than those in London, will be replaced in April 1974. The election of local councils will have taken place twelve months earlier. One would expect such a major change to lead to changes in organisational practices and the development of new organisational forms. For example, the transfer of functions from existing urban authorities to the proposed shire authorities will require the latter authorities to adapt their inherited organisational arrangements. Similarly, the loss of functions will require the reconciliation of existing arrangements with future requirements. In many instances the proposed authorities will be faced with new populations incorporating larger and different clienteles. In some cases there will be no existing arrangements upon which to base the necessary organisation. In all cases there will be the opportunity for—and, more important, an expectation of—organisational change. Within authorities, new central coordination machinery may be created, and changes may take place in, for instance, the numbers and functions of committees and departments. Changes may also take place at the level of the department.
Quality of Anticoagulation Monitoring in Nonvalvular Atrial Fibrillation Patients: Comparison of Anticoagulation Clinic versus Usual Care
Authors: Nichol Michael B , Knight Tara K , Dow Tom , Wygant Gail , Borok Gerald , Hauch Ole , O'Connor Richard
Published: December 2007

Background:

Prior research suggests that receiving specialized anticoagulation services enables patients to achieve better clinical outcomes.

Objective:

To assess the quality of anticoagulation therapy in patents with atrial fibrillation who were enrolled in an anticoagulation clinic (ACC) versus usual care (UC).

Methods:

Using Sharp Rees-Stealy physician group claims data, we estimated time spent in therapeutic range and time to first major bleeding episode or stroke for ACC and UC patients. t-Tests were used to compare time h therapeutic range proportions, and Kaplan-Meier survival analysis was performed to compare rates of bleeding and stroke between groups.

Results:

We identified 1107 patients (351 ACC, 756 UC) treated with anticoagulation therapy for atrial fibrillation with more than one international normalized ratio (INR) reported between March 2001 and March 2004. ACC patients spent a greater proportion (68.14%) of time in therapeutic range compared with UC patients (42.07%; p < 0.001). There was a significant difference between groups in average time between INR tests (ACC = 14.31 days, UC = 18.39 days; p < 0.001). ACC patients were 59% less likely to experience a bleed following the index date than were UC patients (HR = 0.41; 95% CI 0.2444 to 0.6999; p = 0.001), but type of care was not a significant predictor for stroke (HR = 0.95; 95% CI 0.5125 to 1.7777; p value NS).

Conclusions:

Results from this observational study reinforce the positive impact that anticoagulation services have on anticoagulation therapy outcomes, emphasizing the importance of providing such services for patients undergoing treatment with warfarin.
Phosphodiesterase-5 Inhibitors for Lower Urinary Tract Symptoms in Men
Authors: Gales Barry J , Gales Mark A
Published: December 2007

Objective:

To review the efficacy of phosphodiesterase-5 (PDE-5) inhibitors for the treatment of lower urinary tract symptoms in men.

Data Sources:

MEDLINE and International Pharmaceutical Abstracts were searched (1970–August 2007) using the terms phosphodiesterase inhibitor, sildenafil, vardenafil, tadalafil, tower urinary tract symptoms, and benign prostatic hypertrophy.

Study Selection and Data Extraction:

English-language clinical trials, case reports, and background material were evaluated for safety and efficacy data. References of reviewed articles were examined and used to identify additional sources.

Data Synthesis:

Erectile dysfunction (ED) and lower urinary tract symptoms have numerous shared risk factors and are common in aging men. PDE-5 inhibitors may relax urinary tract smooth muscle tissue, which has led to interest in their utility for lower urinary tract symptoms. Six 12 week clinical trials were identified. Three uncontrolled trials (N = 158) examined the effects of on-demand sildenafil ED dosing on lower urinary tract symptoms. The 2 largest trials found that, the greater the ED response, the larger the reduction in lower urinary tract symptoms. A single prospective placebo-controlled trial (N = 369) studied sildenafil 100 mg daily in men with ED and lower urinary tract symptoms. Lower urinary tract symptoms improved significantly in the sildenafil group; patents with the worst lower urinary tract symptoms experienced the greatest benefits. An open-label trial (N = 62) compared daily sildenafil 25 mg, alfuzosin 10 mg, or sildenafil 25 mg plus alfuzosin 10 mg on ED and tower urinary tract symptoms. Combination therapy resulted in greater improvements in ED and lower urinary tract symptoms and urinary flow than did either drug alone. The effects of daily tadalafil 20 mg were studied in 281 men with lower urinary tract symptoms independent of ED. Tadalafil produced statistically significant but clinically modest improvements in tower urinary tract symptoms when compared with placebo.

Conclusions:

PDE-5 inhibitors consistently produced modest reductions in lower urinary tract symptoms. Further studies are needed to fully elucidate the efficacy, cost effectiveness, safety, and appropriate place in therapy of PDE-5 inhibitors. At this time, data are insufficient to routinely recommend chronic use of PDE-5 Inhibitors for tower urinary tract symptoms in men.
Characteristics and Reasons Associated with Nonacceptance of Selective Serotonin-Reuptake Inhibitor Treatment
Authors: Geffen Erica CG van , Hulten Rolf van , Bouvy Marcel L , Egberts Antoine CG , Heerdink Eibert R
Published: December 2007

Background:

Studies have shown that up to 38% of patients who start treatment with antidepressants fill only a single prescription at the pharmacy, apparently not accepting treatment.

Objective:

To determine characteristics and reasons associated with nonacceptance of selective serotonin-reuptake inhibitor (SSRf) treatment,

Methods:

A retrospective study was conducted in 37 community pharmacies in the Netherlands; patients who presented a prescription from a general practitioner (GP) for a newly started SSRI treatment were selected, Nonaccepters were defined as patients who filled only one SSRI prescription; patients who received at least 3 fills of an SSRI prescription were defined as accepters. Patient characteristics were obtained from automated dispensing records and from questionnaires. Areas of evaluation included sociodemographics, disease, and treatment. Nonaccepters were asked their reasons for not filling second prescriptions.

Results:

Of the patients who started SSRI treatment, 22.0% were nonaccepters, filling only a single prescription. Fifty-seven nonaccepters and 128 accepters were included in our analysis. Nonacceptance was more common among patients with a low level of education (OR 2.6; 95% CI 1.1 to 5.9) and in patients who reported nonspecific symptoms like fatigue, stress, and restlessness as the reason for SSRI use (OR 2.7; 95% CI 1.4 to 5.5). Of the nonaccepters, 29.8% (n = 17) did not start SSRI use, and 70.2% (n = 40) discontinued SSRI use within 2 weeks. Fear of adverse effects and the actual occurrence of adverse effects were main reasons for not accepting SSRI treatment. Of the nonaccepters, 55.0% discontinued treatment without informing their GPs.

Conclusions:

Acceptance of SSRI treatment is a decisive moment in a patient's adherence to treatment initiated by his or her GP and deserves more attention; GPs and pharmacists should address treatment issues, especially in groups at risk for nonacceptance.
Cloning, functional analysis, and mitochondrial localization of Trypanosoma brucei monothiol glutaredoxin-1
Authors: Filser Michael , Comini Marcelo A. , Molina-Navarro Maria M. , Dirdjaja Natalie , Herrero Enrique , Krauth-Siegel R. Luise
Published: December 2007

African trypanosomes encode three monothiol glutaredoxins (1-C-Grx1 to 3). 1-C-Grx1 has a putative CAYS active site and Cys181 as single additional cysteine. The recombinant protein forms non-covalent homodimers. As observed for other monothiol glutaredoxins, Trypanosoma brucei 1-C-Grx1 was not active in the glutaredoxin assay with hydroxyethyl disulfide and glutathione nor catalyzed the reduction of insulin disulfide. In addition, it lacked peroxidase activity and did not catalyze protein (de)glutathionylation. Upon oxidation, 1-C-Grx1 forms an intramolecular disulfide bridge and, to a minor degree, covalent dimers. Both disulfide forms are reduced by the parasite trypanothione/tryparedoxin system. 1-C-Grx1 shows mitochondrial localization. The total cellular concentration is at least 5 μm. Thus, 1-C-Grx1 is an abundant protein especially in the rudimentary organelle of the mammalian form of the parasite. Expression of 1-C-Grx1 in Grx5-deficient yeast cells with its authentic presequence targeted the protein to the mitochondria and partially restored the growth phenotype and aconitase activity of the mutant, and conferred resistance against hydroperoxides and diamide. The parasite Grx2 and 3 failed to substitute for Grx5. This is surprising because even bacterial and plant 1-Cys-glutaredoxins efficiently revert the defects, and may be due to the lack of two basic residues conserved in all but the trypanosomatid proteins.
Reassessing the role of a 3′-UTR-binding translational inhibitor in regulation of circadian bioluminescence rhythm in the dinoflagellate Gonyaulax
Authors: Lapointe Mathieu , Morse David
Published: December 2007

The nightly bioluminescence of the dinoflagellate Gonyaulax is a circadian rhythm caused by the presence in cells of specialized bioluminescent organelles, termed scintillons, containing the reaction catalyst luciferase, the substrate luciferin and a luciferin-binding protein (LBP). LBP levels increase at the start of the night phase because of increased protein synthesis rates in vivo, and this regulation has been ascribed to circadian binding of an inhibitory protein factor binding to the 3′ untranslated region (UTR) of lbp mRNA at times when LBP is not normally synthesized. To purify and characterize the binding factor, the electrophoretic mobility shift assays and UV crosslinking experiments used to first characterize the factor were repeated. However, neither these protocols nor binding to biotinylated RNA probes confirmed the presence of a specific circadian RNA-binding protein. Furthermore, neither RNA probe screening of a cDNA library expressed in bacteria nor three-hybrid assays in yeast were successful in isolating a cDNA encoding a protein able to bind specifically to the lbp 3′UTR. Taken together, these results suggest that alternative mechanisms for regulating lbp translation should now be examined.
Cloning, expression and characterization of insulin-degrading enzyme from tomato (Solanum lycopersicum)
Authors: Huet Yoann , Strassner Jochen , Schaller Andreas
Published: December 2007

A cDNA encoding insulin-degrading enzyme (IDE) was cloned from tomato (Solanum lycopersicum) and expressed in Escherichia coli in N-terminal fusion with glutathione S-transferase. GST-SlIDE was characterized as a neutral thiol-dependent metallopeptidase with insulinase activity: the recombinant enzyme cleaved the oxidized insulin B chain at eight peptide bonds, six of which are also targets of human IDE. Despite a certain preference for proline in the vicinity of the cleavage site, synthetic peptides were cleaved at apparently stochastic positions indicating that SlIDE, similar to IDEs from other organisms, does not recognize any particular amino acid motif in the primary structure of its substrates. Under steady-state conditions, an apparent K
m of 62±7 μm and a catalytic efficiency (k
cat/K
m) of 62±15 mm
-1 s-1 were determined for Abz-SKRDPPKMQTDLY(NO3)-NH2 as the substrate. GST-SlIDE was effectively inhibited by ATP at physiological concentrations, suggesting regulation of its activity in response to the energy status of the cell. While mammalian and plant IDEs share many of their biochemical properties, this similarity does not extend to their function in vivo, because insulin and the β-amyloid peptide, well-established substrates of mammalian IDEs, as well as insulin-related signaling appear to be absent from plant systems.
Collagen IV regulates Caco-2 cell spreading and p130Cas phosphorylation by FAK-dependent and FAK-independent pathways
Authors: Sanders Matthew A. , Basson Marc D.
Published: December 2007

We previously observed that collagen IV regulates Caco-2 intestinal epithelial cell spreading and migration via Src-dependent p130Cas phosphorylation and stimulates focal adhesion kinase (FAK). However, the role of FAK and the related kinase, Pyk2, in Caco-2 spreading and migration is unclear. FAK- or Pyk2-specific siRNAs reduced protein levels by 90%. However, when detached cells were replated on collagen IV neither individual nor combined FAK and Pyk2 siRNAs affected the cell spreading rate. As combined FAK and Pyk2 siRNAs increased p130Cas protein levels, we cotransfected cells with 1 nm p130Cas siRNA to partially reduce p130Cas protein to control levels. Although p130Cas Tyr(P)249 phosphorylation was reduced by 60%, cell spreading was unaffected. Combined siRNA reduction of FAK, Pyk2 and p130Cas increased cell spreading by 20% compared to p130Cas siRNA alone, suggesting that FAK and Pyk2 negatively regulate spreading in addition to stimulating spreading via p130Cas. FAK-binding mutant SH3 domain-deleted rat p130Cas was not phosphorylated after adhesion and, unlike full-length p130Cas, did not restore spreading after human-specific p130Cas siRNA knockdown of endogenous p130Cas. Together, these data suggest that FAK positively regulates Caco-2 spreading on collagen IV via p130Cas phosphorylation, but also suggests that FAK may negatively regulate spreading through other mechanisms and the presence of additional FAK-independent pathways regulating p130Cas.