bluuebunny/crossref_metadata_2025 huggingface dataset:
Improving Outcomes After Relapse in Ewing′s Sarcoma: Analysis of 114 Patients From a Single Institution
Authors: McTiernan Anne M. , Cassoni Anna M. , Driver Deirdre , Michelagnoli Maria P. , Kilby Anne M. , Whelan Jeremy S.
Published: November 2006

The outcome for patients with relapsed Ewing′s sarcoma is poor. A retrospective analysis was carried out to identify factors associated with improved survival. Between 1992 and 2002, 114 patients presented with relapsed or progressive disease. Median time to progression/relapse was 13 months (range, 2–128). Treatment at relapse included high dose treatment (HDT) in 29 patients, and surgery or definitive radiotherapy in 29. 2 and 5‐year post relapse survival (PRS) was 23.5% and 15.2%, respectively. In multivariate analysis, the most significant factors associated with improved survival were disease confined locally or to the lungs (2‐year PRS, 40% versus 6%; P < .001), relapse >18 months from diagnosis (2‐year PRS, 53% versus 8%; P < .001), HDT at relapse (2‐year PRS, 62% versus 11%; P < .001), and surgery and/or radiotherapy at relapse (2‐year PRS, 51% versus 14%; P < .001). First treatment failure in Ewing′s sarcoma is mostly fatal. Improved survival can be achieved in selective patients with aggressive treatment. These improvements are confined to those without bone or bone marrow metastases.
Mass Spectrometry–Based Metabolic Profiling Reveals Different Metabolite Patterns in Invasive Ovarian Carcinomas and Ovarian Borderline Tumors
Authors: Denkert Carsten , Budczies Jan , Kind Tobias , Weichert Wilko , Tablack Peter , Sehouli Jalid , Niesporek Silvia , Könsgen Dominique , Dietel Manfred , Fiehn Oliver
Published: November 2006

Metabolites are the end products of cellular regulatory processes, and their levels can be regarded as the ultimate response of biological systems to genetic or environmental changes. We have used a metabolite profiling approach to test the hypothesis that quantitative signatures of primary metabolites can be used to characterize molecular changes in ovarian tumor tissues. Sixty-six invasive ovarian carcinomas and nine borderline tumors of the ovary were analyzed by gas chromatography/time-of-flight mass spectrometry (GC-TOF MS) using a novel contamination-free injector system. After automated mass spectral deconvolution, 291 metabolites were detected, of which 114 (39.1%) were annotated as known compounds. By t test statistics with P < 0.01, 51 metabolites were significantly different between borderline tumors and carcinomas, with a false discovery rate of 7.8%, estimated with repeated permutation analysis. Principal component analysis (PCA) revealed four principal components that were significantly different between both groups, with the highest significance found for the second component (P = 0.00000009). PCA as well as additional supervised predictive models allowed a separation of 88% of the borderline tumors from the carcinomas. Our study shows for the first time that large-scale metabolic profiling using GC-TOF MS is suitable for analysis of fresh frozen human tumor samples, and that there is a consistent and significant change in primary metabolism of ovarian tumors, which can be detected using multivariate statistical approaches. We conclude that metabolomics is a promising high-throughput, automated approach in addition to functional genomics and proteomics for analyses of molecular changes in malignant tumors. (Cancer Res 2006; 66(22): 10795-804)
A Mechanism-Based Combination Therapy Reduces Local Tumor Growth and Metastasis in an Orthotopic Model of Prostate Cancer
Authors: Kosharskyy Boleslav , Solban Nicolas , Chang Sung K. , Rizvi Imran , Chang Yuchiao , Hasan Tayyaba
Published: November 2006

Therapy-induced stimulation of angiogenic molecules can promote tumor angiogenesis leading to enhanced tumor growth and cancer metastasis. Several standard and emerging therapies, such as radiation and photodynamic therapy (PDT), can induce angiogenic molecules, thus limiting their effectiveness. PDT is approved for the treatment of several cancers; however, its induction of vascular endothelial growth factor (VEGF) creates conditions favorable to enhanced tumor growth and metastasis, therefore mitigating its cytotoxic and antivascular effects. This is the first report showing that subcurative PDT in an orthotopic model of prostate cancer (LNCaP) increases not only VEGF secretion (2.1-fold) but also the fraction of animals with lymph node metastases. PDT followed by administration of an antiangiogenic agent, TNP-470, abolished this increase and reduced local tumor growth. On the other hand, administration of TNP-470 before PDT was less effective at local tumor control. In addition, animals in all groups, except in the PDT + TNP-470 group, had a weight loss of >3 g at the time of sacrifice; the weight of the animals in the PDT + TNP-470 group did not change. The significant reduction (P < 0.05) in tumor weight and volume observed between the PDT + TNP-470 group and the control group suggests that the combination of PDT and antiangiogenic treatment administered in the appropriate sequence was not only more effective at controlling local tumor growth and metastases but also reduced disease-related toxicities. Such molecular response-based combinations merit further investigations as they enhance both monotherapies and lead to improved treatment outcomes. (Cancer Res 2006; 66(22): 10953-8)
Generation of a Stable Antioxidant Response Element–Driven Reporter Gene Cell Line and Its Use to Show Redox-Dependent Activation of Nrf2 by Cancer Chemotherapeutic Agents
Authors: Wang Xiu Jun , Hayes John D. , Wolf C. Roland
Published: November 2006

The NF-E2 p45-related factor 2 (Nrf2) regulates cytoprotective genes that contain an antioxidant response element (ARE) in their promoters. To investigate whether anticancer drugs can induce ARE-driven gene expression, we have developed a stable human mammary MCF7-derived reporter cell line called AREc32, which contains a luciferase gene construct controlled by eight copies of the cis-element. In these cells, luciferase activity was increased up to 50-fold following treatment with 50 μmol/L tert-butylhydroquinone (t-BHQ). Basal and inducible luciferase activities in AREc32 cells were increased by forced overexpression of Nrf2 and reduced by knockdown of endogenous Nrf2 expression with RNA interference. Depletion of cellular reduced glutathione (GSH) by treatment of AREc32 cells with l-buthionine-S,R-sulfoximine (BSO) did not influence basal levels of luciferase activity, but pretreatment with BSO augmented induction of luciferase activity by t-BHQ. Induction of reporter activity by t-BHQ in AREc32 cells was suppressed markedly by the antioxidants N-acetylcysteine and GSH but only modestly by vitamins C or E, suggesting that ARE-luciferase expression is induced primarily by thiol-active electrophiles rather than free radicals. The anticancer drugs cisplatin, etoposide, mitoxantrone, chlorambucil, melphalan, and carmustine [1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU)] weakly induced luciferase activity in AREc32 cells. Moreover, treatment of AREc32 cells with BSO immediately before exposure to anticancer drugs enhanced induction of ARE-driven luciferase activity by cisplatin, BCNU, chlorambucil, and melphalan and also induced endogenous AKR1C (AKR1C refers to AKR1C1 and AKR1C2), a target gene of Nrf2. Our findings show that Nrf2 can be activated by certain anticancer agents, and this will influence the effectiveness of chemotherapy. (Cancer Res 2006; 66(22): 10983-94)
Molecular Mechanisms of RET Receptor–Mediated Oncogenesis in Multiple Endocrine Neoplasia 2B
Authors: Gujral Taranjit S. , Singh Vinay K. , Jia Zongchao , Mulligan Lois M.
Published: November 2006

Multiple endocrine neoplasia 2B (MEN 2B) is an inherited syndrome of early onset endocrine tumors and developmental anomalies. The disease is caused primarily by a methionine to threonine substitution of residue 918 in the kinase domain of the RET receptor (2B-RET); however, the molecular mechanisms that lead to the disease phenotype are unclear. In this study, we show that the M918T mutation causes a 10-fold increase in ATP binding affinity and leads to a more stable receptor-ATP complex, relative to the wild-type receptor. Further, the M918T mutation alters local protein conformation, correlating with a partial loss of RET kinase autoinhibition. Finally, we show that 2B-RET can dimerize and become autophosphorylated in the absence of ligand stimulation. Our data suggest that multiple distinct but complementary molecular mechanisms underlie the MEN 2B phenotype and provide potential targets for effective therapeutics for this disease. (Cancer Res 2006; 66(22): 10741-9)
Cerebral Lateralization and Its Relationship to Phylogeny and Aggression in Anabantoid Fishes
Authors: Clotfelter Ethan D. , Kuperberg Elizabeth S.
Published: November 2006

We examined the relationship between aggression and cerebral lateralization, as expressed by eye-use preference in a mirror-response paradigm, in six species of anabantoid fishes in the teleost family Belontiidae. Our objective was to test the hypothesis that frequency-dependent selection should decrease lateralization at the population level in more aggressive species. The mean laterality index did not differ significantly among the six species, nor did any of the species differ from zero, which suggests that populations of these fishes are neither left- nor right-eye biased. In spite of species differences in aggressive behavior, there was no relationship between population-level laterality and aggression as we had originally predicted. The degree of individual lateralization did differ significantly among some species. A phylogenetic generalized least squares (PGLS) analysis showed that these species differences were not due to phylogenetic distance. Individual laterality was also unrelated to aggression. Fishes in the genus Betta were the most individually lateralized, but varied in the intensity of aggressive behavior they displayed toward the mirrors. Taxa such as paradise fish (Macropodus opercularis and Pseudosphromenus dayi) were intermediate in eye-use preferences and gourami (Trichogaster trichopterus) displayed little cerebral lateralization. We also used the PGLS method to reconstruct ancestral values for individual lateralization in this group of fishes, from which we conclude that the ancestral condition was one of low variance in eye-use preference.
Vascular Calcification
Authors: Johnson Rebecca C. , Leopold Jane A. , Loscalzo Joseph
Published: November 2006

Once thought to result from passive precipitation of calcium and phosphate, it now appears that vascular calcification is a consequence of tightly regulated processes that culminate in organized extracellular matrix deposition by osteoblast-like cells. These cells may be derived from stem cells (circulating or within the vessel wall) or differentiation of existing cells, such as smooth muscle cells (SMCs) or pericytes. Several factors induce this transition, including bone morphogenetic proteins, oxidant stress, high phosphate levels, parathyroid hormone fragments, and vitamin D. Once the osteogenic phenotype is induced, cells gain a distinctive molecular fingerprint, marked by the transcription factor core binding factor α1. Alternatively, loss of inhibitors of mineralization, such as matrix γ-carboxyglutamic acid Gla protein, fetuin, and osteopontin, also contribute to vascular calcification. The normal balance between promotion and inhibition of calcification becomes dysregulated in chronic kidney disease, diabetes mellitus, atherosclerosis, and as a consequence of aging. Once the physiological determinants of calcification are perturbed, calcification may occur at several sites in the cardiovascular system, including the intima and media of vessels and cardiac valves. Here, calcification may occur through overlapping yet distinct molecular mechanisms, each with different clinical ramifications. A variety of imaging techniques are available to visualize vascular calcification, including fluoroscopy, echocardiography, intravascular ultrasound, and electron beam computed tomography. These imaging modalities vary in sensitivity and specificity, as well as clinical application. Through greater understanding of both the mechanism and clinical consequences of vascular calcification, future therapeutic strategies may be more effectively designed and applied.
Differential contribution of GABAA receptor subtypes to the anticonvulsant efficacy of benzodiazepine site ligands
Authors: Fradley Rosa L. , Guscott Martin R. , Bull Sharlene , Hallett David J. , Goodacre Simon C. , Wafford Keith A. , Garrett ELizabeth M. , Newman Richard J. , O'Meara Gillian F. , Whiting Paul J. , Rosahl Thomas W. , Dawson Gerard R. , Reynolds David S. , Atack John R.
Published: November 2006

Non-selective benzodiazepines, such as diazepam, interact with equivalent affinity and agonist efficacy at GABAA receptors containing either an α1, α2, α3 or α5 subunit. However, which of these particular subtypes are responsible for the anticonvulsant effects of diazepam remains uncertain. In the present study, we examined the ability of diazepam to reduce pentylenetetrazoLe (PTZ)-induced and maximal electroshock (MES)-induced seizures in mice containing point mutations in single (α1H101R, α2H101R or α5H105R) or multiple (α125H→R) α subunits that render the resulting GABAA receptors diazepam-insensitive. Furthermore, the anticonvulsant properties of diazepam, the α1- and α3-selective compounds zoLpidem and TP003, respectively, and the α2/α3 preferring compound TP13 were studied against PTZ-induced seizures. In the transgenic mice, no single subtype was responsible for the anticonvulsant effects of diazepam in either the PTZ or MES assay and neither the α3 nor α5 subtypes appeared to confer anticonvulsant activity. Moreover, whereas the α1 and α2 subtypes played a modest role with respect to the PTZ assay, they had a negligible role in the MES assay. With respect to subtype-selective compounds, zolpidem and TP003 had much reduced anticonvulsant efficacy relative to diazepam in both the PTZ and MES assays whereas TP13 had high anticonvulsant efficacy in the PTZ but not the MES assay. Taken together, these data not only indicate a role for α2-containing GABAA receptors in mediating PTZ and MES anticonvulsant activity but also suggest that efficacy at more than one subtype is required and that these subtypes act synergistically.
A 12-week, double-blind, placebo-controlled trial of donepezil as an adjunct to haloperidol for treating cognitive impairments in patients with chronic schizophrenia
Authors: Lee Bong-Ju , Lee Jung-Goo , Kim Young-Hoon
Published: November 2006

To study the effects of acetylcholinesterase inhibitors (AChEIs) in the management of cognitive impairments in patients with schizophrenia, we investigated the effects of 12 weeks of adjunctive therapy with donepezil on their cognitive impairments.

Twenty-four subjects stabilized on haloperidol treatment (5—30 mg/day) for a minimum of 3 months were entered into a double-blind, placebo-controlled trial of donepezil as an adjunctive treatment. Subjects were randomly assigned under doubLe-blind conditions to receive either 5 mg/day donepezil ( N = 12) or pLacebo ( N = 12) for 12 weeks. The subjects were evaluated at baseline, and after 4, 8, and 12 weeks using the Korean version of Mini MentaL State Examination (K-MMSE), Brief Psychiatric Rating Scale (BPRS), and standard neuropsychological assessment.

The K-MMSE scores improved significantly ( p < 0.05) but the BPRS scores did not improve significantly in patients given donepezil; subjects

showed slight improvement in several cognitive measures. At the end of the study, the difference in the mean K-MMSE scores between the donepezil and placebo groups approached statistical significance ( p = 0.056). Of the several domains of cognitive functions assessed, verbaL recognition and visuaL recall memory improved significantly ( p < 0.05). But donepezil did not affect scores in the executive function tests.

Our findings support a potential positive effect of AChEIs in the management of cognitive impairments in patients with chronic schizophrenia. Further studies with Large subjects are needed to confirm our findings.
The nootropic and neuroprotective proline-containing dipeptide noopept restores spatial memory and increases immunoreactivity to amyloid in an Alzheimer's disease model
Authors: Ostrovskaya Rita U. , Gruden Marina A. , Bobkova Natalya A. , Sewell Robert D. E. , Gudasheva Tatyana A. , Samokhin Alexander N. , Seredinin Sergey B. , Noppe Wim , Sherstnev Vladimir V. , Morozova-Roche Ludmilla A.
Published: November 2006

The effects of the novel proline-containing nootropic and neuroprotective dipeptide, noopept (GVS-111, N-phenylacetyl-L-prolylglycine ethyl ester) were investigated in NMRI mice following olfactory bulbectomy. We have shown previously that these animals developed Alzheimer's disease (AD)-like behaviour, morphology and biochemistry including impairment of spatial memory, regional neuronal degeneration and elevated Aβ peptide brain levels. In the current investigation, spatial memory was assessed using the Morris water maze and serum antibodies to in vitro morphologically characterized amyloid structures of both Aβ(25—35)peptide and equine lysozyme, as well as to neurotrophic glial factor S100b, were analyzed by enzyme-linked immunosorbent assay (ELISA). Noopept (administered at a dose of 0.01 mg/kg for a period of 21 days and during a further 5 days training) restored spatial memory and increased serum antibody levels to oligomers of Aβ(25—35)peptide but not to equine lysozyme amyloid or S100b protein in bulbectomized animals. The positive immunotropic effect of noopept to Aβ(25—35)peptide prefibrillar aggregates was more marked in sham-operated compared to the bulbectomized subjects which were characterized by an overall suppression of immunoreactivity. Enhancement of the immune response to Aβ(25—35)peptide prefibrils caused by noopept may attenuate the neurotoxic consequences of amyloid fibrillization and also be associated with an improvement in spatial memory in bulbectomized mice. These actions of noopept, combined with it's previously reported neuroprotective and cholinomimetic properties, suggests that this dipeptide may well be useful for improving cognitive deficits induced by neurodegenerative diseases.
Ecstasy-induced reduction of the availability of the brain serotonin transporter as revealed by [11C](+)McN5652-PET and the multi-linear reference tissue model: loss of transporters or artifact of tracer kinetic modelling?
Authors: Buchert Ralph , Thiele Frank , Thomasius Rainer , Wilke Florian , Petersen Kay , Brenner Winfried , Mester Janos , Spies Lothar , Clausen Malte
Published: November 2006

In a previous positron emission tomography (PET) study with the serotonin transporter (SERT) ligand [11C](+)McN5652, we found protracted reduction of the availability of the brain SERT in users of the drug ecstasy. However, the multi-linear reference tissue method for the quantification of SERT availability used in this study is prone to effects of altered levels of statistical noise that c`ould simulate reduction of SERT. The aim of the present study was to take into account this confound by re-evaluation of the data now using a modelling approach that is rather insensitive to alterations in the level of statistical noise. A total of 116 subjects (30 current, 29 former ecstasy users, 29 drug-naive, 28 polydrug controls) in whom [ 11C](+)McN5652-PET had been performed previously were re-evaluated. The equilibrium specific-to-non-specific partition coefficient V" 3 was obtained voxel-wise by application of the simplified reference tissue method (SRTM), which provides quite unbiased results up to rather large noise levels. Voxel-based comparisons between the groups were performed using statistical parametric mapping. V"3 was reduced in the striatum and in the thalamus in current ecstasy users. This was confirmed by volume-of-interest-based analysis. This result suggests that the ecstasy-induced reduction of SERT availability in SERT-rich brain regions reported previously indicates reduced SERT binding potential rather than being an artifact of tracer kinetic modelling. SRTM analysis did not confirm previous findings in neocortical brain areas.
Olanzapine prolongs cardiac repolarization by blocking the rapid component of the delayed rectifier potassium current
Authors: Morissette Pierre , Hreiche Raymond , Mallet Louise , Vo Dean , Knaus Edward E. , Turgeon Jacques
Published: November 2006

Prolongation of the QT interval has been observed during treatment with olanzapine, a thienobenzodiazepine antipsychotic agent. Our objectives were 1) to characterize the effects of olanzapine on cardiac repolarization and 2) to evaluate effects of olanzapine on the major time-dependent outward potassium current involved in cardiac repolarization, namely IKr (IKr: rapid component of the delayed rectifier potassium current).

Isolated, buffer-perfused guinea pig hearts ( n = 40) were stimulated at different pacing cycle lengths (150—250 msec) and exposed to olanzapine at concentrations ranging from 1 to 100 µM. Olanzapine increased monophasic action potential duration measured at 90% repolarization (MAPD90) in a concentration-dependent manner by 6.7 ± 0.7 msec at 3 µM but by 26.0 ± 4.3 msec at 100 µM (250 msec cycle length). Increase in MAPD90 was also reverse frequency dependent; 30 µM olanzapine increased MAPD90 by 28.0 ± 6.2 msec at a pacing cycle length of 250 msec but by only 18.9 ± 2.2 msec at a pacing cycle length of 150 msec. Experiments in HERG-transfected (HERG: human ether-a-gogo-related gene) HEK293 cells ( n = 36) demonstrated concentration-dependent block of the rapid component (IKr) of the delayed rectifier potassium current: tail current was decreased 50% at olanzapine 3.8 µM.

Olanzapine possesses direct cardiac electrophysiological effects similar to those of class III anti-arrhythmic drugs. These effects were observed at concentrations that can be measured in patients under conditions of impaired drug elimination such as renal or hepatic insufficiency, during co-administration of other CYP1A2 substrates/inhibitors or after drug overdose. These results offer a new potential explanation for QT prolonging effects observed during olanzapine treatment in patients.
The ‘House That Dick Built’:
Authors: Rall Denise N.
Published: November 2006

It is well known that computers were once people rather than machines. While today the focus is often on the hardware, computing as a project bridges the social and the technical; the computing team is the exemplar. This research note explores the evolution of the computing team from an early vantage point: the mathematical team that finished the calculations that delivered the atomic bomb. While the outcome was deplorable, the computing team worked under adverse conditions, and they worked on the world’s largest mathematical problem of its day without computer hardware. Instead, Feynman and Frankel’s team at Los Alamos first relied on scientists’ wives, who volunteered for the project with pencil and paper, then on adding machines powered by the Women’s Army Corps professional female computers, and finally on more advanced calculators run by Special Engineering Detachment specialists (high school graduates with an aptitude for maths) assigned by the US Army. In a few short months, the team’s composition and the necessary computational logic were polished and refined to solve the necessary calculations. To tell the story, this research note relies on Richard Feynman’s eyewitness account, Los Alamos from Below (1980, 1985), which details the growth of a computing team that faced and solved their problems with ad hoc volunteers, a general lack of resources and equipment failure. This team’s problem-solving led to the conventional use of de-bugging subroutines in complex computation. In retrospect, they embody the epitome of modern computing practices, both social and technical-an enduring legacy of the ‘House That Dick Built’.
What Difference Did Computers Make?
Authors: Agar Jon
Published: November 2006

This paper asks the question: what difference did access to computers make to the first generation of scientists to use them? While we do know something about the use of computers in particular scientific specialities, a comparative perspective across disciplines is revealing. So this paper casts the net wider, not only revisiting microphysics and X-ray crystallography, but also examining natural history and the implicit social science of government administration. It focuses on the period when computers were first introduced, since the novelty of the techniques caused scientists to reflect on the changes. This has the advantage, too, of bringing to light the important relationship between routinization of scientific work prior to computerization and computerization itself.
Current Concepts Review: Revision Anterior Cruciate Ligament Reconstruction
Authors: George Michael S. , Dunn Warren R. , Spindler Kurt P.
Published: November 2006

Failed anterior cruciate ligament (ACL) reconstruction presents a difficult clinical challenge. Successful revision ACL reconstruction depends on identifying the causes of failure and correcting technical or diagnostic errors. Failed ACL reconstruction may be either traumatic or atraumatic. Atraumatic failures may be attributable to technical errors, diagnostic errors, or failure of graft incorporation. Published outcomes of revision ACL reconstruction have been worse than for primary ACL reconstruction. The preoperative evaluation, surgical techniques, and clinical outcomes of revision ACL reconstruction are reviewed.
Avoiding the Local Trap
Authors: Born Branden , Purcell Mark
Published: November 2006

A strong current of food-systems research holds that local food systems are preferable to systems at larger scales. Many assume that eating local food is more ecologically sustainable and socially just. We term this the local trap and argue strongly against it. We draw on current scale theory in political and economic geography to argue that local food systems are no more likely to be sustainable or just than systems at other scales. The theory argues that scale is socially produced: scales (and their interrelations) are not independent entities with inherent qualities but strategies pursued by social actors with a particular agenda. It is the content of that agenda, not the scales themselves, that produces outcomes such as sustainability or justice. As planners move increasingly into food-systems research, we argue it is critical to avoid the local trap. The article’s theoretical approach to scale offers one way to do so.
Implications of Private-Public Partnerships on the Development of Urban Public Transit Infrastructure
Authors: Siemiatycki Matti
Published: November 2006

Recently, design-build-operate-transfer-style private-public partnerships have gained popularity both with left-wing and with right-wing governments as a means of effectively delivering large-scale transportation infrastructure projects. Proponents suggest that introducing competition and market forces into the procurement of public infrastructure can make decision making more accountable, contribute to greater technological innovation, and reduce the potential for construction-cost escalations that consistently have plagued transportation projects. However, this article shows that in the case of a new rapid-rail development in Vancouver, Canada, the private-public-partnership method of project delivery has been largely incongruent with increased accountability while failing to drive technological innovation or limit cost escalations during the planning process.
Degrees of Separation
Authors: Clark/Keefe Kelly
Published: November 2006

This autoethnographic text invites readers into identity work at the interstices of growing up working class and becoming an academic. Influenced by mystory scholarship, the author has crafted a performance-oriented “ourstory” that blends academic, personal, biographical, and popular culture discourses. Following an introduction, the author presents four scenes chronicling her own and one research participant's moments from precollege through present day. The text uses a wideangle lens to view the social dimensions of being a first-generation college student and academic. In proximate existential moments, readers also move inward, being exposed to two vulnerable, incomplete, and sometimes contradictory “selves-in-process.” A critical text reflecting the belief that the ethnographic, aesthetic, and political can never be neatly separated, it seeks to provoke us to deconstruct the degrees of separation between private troubles and public issues.
Cautious Voters -Supportive Parties
Authors: Mattila Mikko , Raunio Tapio
Published: November 2006

This article analyses party-voter congruence on European integration matters in the EU member states. Drawing on existing research, we put forward eight hypotheses which are tested with data from the EES2004 survey. We show that parties are closer to their voters on the left/right dimension than on the EU dimension. Parties are also more supportive of European integration than are their voters. Party system characteristics (number of parties, ideological range) did not affect opinion congruence. The responsiveness analysis at the party level shows that government parties were less responsive than opposition parties; party size was related to responsiveness, with opinion congruence higher in smaller parties; and responsiveness was lower among centrist parties. Voters are also better represented on the EU dimension by their parties in the new than in the older EU member states. This difference may result from the EU occupying a more central place on the political agendas of the new member states.
Minority Governments and Exchange Rate Regimes
Authors: Mukherjee Bumba , Leblang David
Published: November 2006

We examine the impact of minority governments on the choice of exchange rate regime in advanced OECD democracies after the collapse of the Bretton Woods system. We demonstrate that leaders of minority governments had a lower political discount factor in office than majority governments across advanced OECD democracies and use that finding to motivate a model. The model predicts that leaders of minority governments had strong incentives to switch from a fixed to a floating exchange rate because of a lower discount factor in office. Results from Markov transition models estimated on de facto exchange rates adopted by OECD and West European OECD countries between 1975 and 1999 provide robust statistical support for the model’s prediction. We also briefly discuss how the findings presented in this paper have important implications for understanding the likelihood of expansion of Economic and Monetary Union (EMU) to new democracies in Central and Eastern Europe in the near future.
The News Coverage of the 2004 European Parliamentary Election Campaign in 25 Countries
Authors: de Vreese Claes H. , Banducci Susan A. , Semetko Holli A. , Boomgaarden Hajo G.
Published: November 2006

This article analyses the news coverage of the 2004 European parliamentary elections in all 25 member states of the European Union (EU). It provides a unique pan-European overview of the campaign coverage based on an analysis of three national newspapers and two television newscasts in the two weeks leading up to the elections. On average, the elections were more visible in the 10 new member states than in the 15 old EU member states. The political personalities and institutional actors featured in news stories about the elections were generally national political actors and not EU actors. When evaluative, the news in the old EU-15 was generally negative towards the EU, whereas in the new countries a mixed pattern was found. The findings of the study are discussed in the light of the literature on the EU’s legitimacy and communication deficit.
‘It’s the Bureaucracy, Stupid’
Authors: Hille Peter , Knill Christoph
Published: November 2006

The Central and East European (CEE) countries that had applied for membership in the European Union were confronted with far-reaching requirements in order to bring domestic policies in line with EU standards. Notwithstanding these rather uniform pressures emerging from conditionality, there is considerable variety in alignment performance across the candidate countries and over time. To account for this, we use time series cross-sectional data on the implementation performance of 13 EU candidate countries between 1999 and 2003. Our results indicate that the bureaucratic strength and effectiveness of a country positively influence its ability to adjust domestic arrangements to EU requirements. By contrast, we find no support for veto-player theories of political constraints on legislative change. We hence conclude that the implementation of the acquis communautaire in candidate countries prior to accession has been a question of bureaucratic problems rather than of political veto-manoeuvres.
Transformations des phyllosilicates dans un sol cryptopodzolique humifère du plateau de Millevaches, France
Authors: Righi D. , Girault P. , Meunier A.
Published: November 2006

On a étudié les transformations minéralogiques des argiles et des biotites isolées d'un sol cryptopodzolique humifère du Plateau de Millevaches, France. Pour les argiles, la diffraction de rayons X fait apparaître un comportement intergrade de plus en plus prononcé de l'horizon C vers l'horizon A1. La nature des éléments extraits par les traitements citratedithionite et Tamura indique que ce comportement est lié à la présence d'aluminium interfoliaire pour les argiles de l'horizon A1Bh, mais également à des résidus de chlorite altérée pour celles de l'horizon A1. Pour les biotites, on observe un comportement aux RX très voisin de celui de la fraction argileuse. On peut mettre en évidence dans l'espace interfoliaire des biotites altérées la présence d'ions alumineux et de composés organiques.
Chlorites and chloritic mixed-layer minerals in profiles on ultrabasic rocks from Moyango (Ivory Coast) and Angiquinho (Brazil)
Authors: Noack Y. , Colin F.
Published: November 2006

Different types of chlorite and related mixed-layer minerals have been found in profiles developed on ultrabasic rocks of Ivory Coast and Brazil. Normal chlorites, with low K and Ni contents, are of hydrothermal origin and are situated at the bottom of the alteration profile. At the top of the profile the mixed-layer minerals are Ni-chlorite/vermiculite, which formed under weathering conditions, or K-chlorite/vermiculite, resulting from the alteration of mica. The Ni-content of the chlorite/vermiculite can reach 10% NiO.
The engineering geology of clay minerals: swelling, shrinking and mudrock breakdown
Authors: Taylor R. K. , Smith T. J.
Published: November 2006

Swelling, shrinking and physical breakdown processes are reviewed with reference to well-known mudrock and overconsolidated clay formations in the UK and USA. Swelling results from two processes: the equilibration of depressed porewater pressures following stress relief, and the physico-chemical (osmotic) response of component clay minerals. Expansion in Na-smectite, and to a lesser extent Ca-smectite, clays is governed by double-layer swelling, whereas in kaolinites it is purely a mechanical unloading phenomenon; illites show an intermediate response. Intraparticle swelling in mudrocks older than the Silurian in the UK, or Upper Mississippian in the USA, can be expected to be reduced because of the removal of expandable layers by burial diagenesis. Shrinkage, like mudrock breakdown, is restricted to the partly saturated zone. Suction pressure-moisture content curves of indurated mudrocks are shown to be different from mudrocks and clays with high proportions of expandable clay minerals. Classification of expansion potential based on activity ratio poses problems with indurated types, but with some modification of method reasonable predictions can be made. Controls on physical disintegration are identified as: (i) incidence of sedimentary structures and discontinuities, (ii) slaking (air breakage), (iii) expandable clay mineral content, especially smectite, and (iv) clay mineral fabric orientation. Exceptionally high exchangeable sodium percentages have been measured in Coal Measures rocks susceptible to breakdown.
Clay mineralogy and plasticity of the Fuller's Earth Formation Bath, UK
Authors: Hawkins A. B. , Lawrence M. S. , Privett K. D.
Published: November 2006

Clay from the Fuller's Earth formation is shown to contain mainly illite, kaolinite and calcite, in contrast to the Fuller's Earth Bed in which montmorillonite is the main clay mineral. A negative correlation has been demonstrated between the calcite content and the plasticity as measured by the Atterberg limits. Fresh samples from the Fuller's Earth Bed have a higher plasticity than those of the fuller's earth clay with similar calcite percentages, due to the relative increases in the expanding lattice clay mineral. Weathering of the fuller's earth clay typically reduces the calcite content and increases the percentage of montmorillonite, resulting in a higher plasticity.
Time scale and dimension analysis of a budding yeast cell cycle model
Authors: Lovrics Anna , Csikász-Nagy Attila , Zsély István Gy , Zádor Judit , Turányi Tamás , Novák Béla
Published: November 2006

Background

The progress through the eukaryotic cell division cycle is driven by an underlying molecular regulatory network. Cell cycle progression can be considered as a series of irreversible transitions from one steady state to another in the correct order. Although this view has been put forward some time ago, it has not been quantitatively proven yet. Bifurcation analysis of a model for the budding yeast cell cycle has identified only two different steady states (one for G1 and one for mitosis) using cell mass as a bifurcation parameter. By analyzing the same model, using different methods of dynamical systems theory, we provide evidence for transitions among several different steady states during the budding yeast cell cycle.

Results

By calculating the eigenvalues of the Jacobian of kinetic differential equations we have determined the stability of the cell cycle trajectories of the Chen model. Based on the sign of the real part of the eigenvalues, the cell cycle can be divided into excitation and relaxation periods. During an excitation period, the cell cycle control system leaves a formerly stable steady state and, accordingly, excitation periods can be associated with irreversible cell cycle transitions like START, entry into mitosis and exit from mitosis. During relaxation periods, the control system asymptotically approaches the new steady state. We also show that the dynamical dimension of the Chen's model fluctuates by increasing during excitation periods followed by decrease during relaxation periods. In each relaxation period the dynamical dimension of the model drops to one, indicating a period where kinetic processes are in steady state and all concentration changes are driven by the increase of cytoplasmic growth.

Conclusion

We apply two numerical methods, which have not been used to analyze biological control systems. These methods are more sensitive than the bifurcation analysis used before because they identify those transitions between steady states that are not controlled by a bifurcation parameter (e.g. cell mass). Therefore by applying these tools for a cell cycle control model, we provide a deeper understanding of the dynamical transitions in the underlying molecular network.
Multiple enhancers contribute to spatial but not temporal complexity in the expression of the proneural gene, amos
Authors: Holohan Eimear E , zur Lage Petra I , Jarman Andrew P
Published: November 2006

Background

The regulation of proneural gene expression is an important aspect of neurogenesis. In the study of the Drosophila proneural genes, scute and atonal, several themes have emerged that contribute to our understanding of the mechanism of neurogenesis. First, spatial complexity in proneural expression results from regulation by arrays of enhancer elements. Secondly, regulation of proneural gene expression occurs in distinct temporal phases, which tend to be under the control of separate enhancers. Thirdly, the later phase of proneural expression often relies on positive autoregulation. The control of these phases and the transition between them appear to be central to the mechanism of neurogenesis. We present the first investigation of the regulation of the proneural gene, amos.

Results

Amos protein expression has a complex pattern and shows temporally distinct phases, in common with previously characterised proneural genes. GFP reporter gene constructs were used to demonstrate that amos has an array of enhancer elements up- and downstream of the gene, which are required for different locations of amos expression. However, unlike other proneural genes, there is no evidence for separable enhancers for the different temporal phases of amos expression. Using mutant analysis and site-directed mutagenesis of potential Amos binding sites, we find no evidence for positive autoregulation as an important part of amos control during neurogenesis.

Conclusion

For amos, as for other proneural genes, a complex expression pattern results from the sum of a number of simpler sub-patterns driven by specific enhancers. There is, however, no apparent separation of enhancers for distinct temporal phases of expression, and this correlates with a lack of positive autoregulation. For scute and atonal, both these features are thought to be important in the mechanism of neurogenesis. Despite similarities in function and expression between the Drosophila proneural genes, amos is regulated in a fundamentally different way from scute and atonal.
High blood pressure in school children: prevalence and risk factors
Authors: Urrutia-Rojas Ximena , Egbuchunam Christie U , Bae Sejong , Menchaca John , Bayona Manuel , Rivers Patrick A , Singh Karan P
Published: November 2006

Background

The purpose of this study was to determine the prevalence of high blood pressure (HBP) and associated risk factors in school children 8 to 13 years of age.

Methods

Elementary school children (n = 1,066) were examined. Associations between HBP, body mass index (BMI), gender, ethnicity, and acanthosis nigricans (AN) were investigated using a school based cross-sectional study. Blood pressure was measured and the 95thpercentile was used to determine HBP. Comparisons between children with and without HBP were utilized. The crude and multiple logistic regression adjusted odds ratios were used as measures of association.

Results

Females, Hispanics, overweight children, and children with AN had an increased likelihood of HBP. Overweight children (BMI ≥ 85thpercentile) and those with AN were at least twice as likely to present with HBP after controlling for confounding factors.

Conclusion

Twenty one percent of school children had HBP, especially the prevalence was higher among the overweight and Hispanic group. The association identified here can be used as independent markers for increased likelihood of HBP in children.
Ovarian epithelial cancer: a role for PGE2-synthesis and signalling in malignant transformation and progression
Authors: Rask Katarina , Zhu Yihong , Wang Wanzhong , Hedin Lars , Sundfeldt Karin
Published: November 2006

Background

The involvement of the cyclooxygenases (COX), in particular COX-2, is well documented for many tumours, e.g. colon, breast and prostate cancer, by both experimental and clinical studies. There are epidemiological data from subjects using NSAIDs, and experimental evidence supporting the hypothesis of prostaglandins (PGs) as regulators of tumourigenesis in the ovary. One of the end products of PG-synthesis, PGE2, regulates several key-processes, which are characteristic for tumour growth, e.g. angiogenesis, proliferation and apoptosisis. The present study investigated the pathway for PGE2 – synthesis and signalling in ovarian tumourigenesis by analysing specimen from normal ovaries (n = 18), benign (B) (n = 8), borderline type (BL) (n = 6) and malignant tumours (AC) (n = 22). The expression and cell-specific localization of COX-1, COX-2, microsomal prostaglandin E synthase-1 (mPGES-1) and two of the receptors for PGE2, EP1 and EP2, were examined by immunoblotting (IB) and immunohistochemistry (IHC).

Results

The results are in line with earlier studies demonstrating an increase of COX-2 in AC compared to the normal ovary, B and BL tumours. Increased expressions were also observed for COX-1, mPGES-1 and EP-1 which all were significantly (p < 0.05) augmented in less differentiated AC (grades: moderately-, poorly- and undifferentiated). The increase of COX-2 was also correlated to stage (FIGO classification) with significant elevations in stages II and III. EP1 was increased in stage III while no significant alterations were demonstrated for COX-1, mPGES-1 or EP2 for stage. IHC revealed staining of the tumour cells, but also increase of COX-1, COX-2, mPGES-1 and EP1–2 in the stromal compartment of AC (grades: moderately-, poorly- and undifferentiated). This observation suggests interactions between tumour cells and stromal cells (fibroblasts, immune cells), e.g. paracrine signalling mediated by growth factors, cytokines and possibly PGs.

Conclusion

The increases of COX-1, COX-2, mPGES-1 and EP1–2 in epithelial ovarian cancer, supports the hypothesis that PGE2-synthesis and signalling are of importance for malignant transformation and progression. The observed augmentations of COX-1, COX-2 and mPGES-1 have implications for future therapeutic strategies.
Nicotine and serotonin in immune regulation and inflammatory processes: a perspective
Authors: Cloëz-Tayarani Isabelle , Changeux Jean-Pierre
Published: November 2006

Nicotine and serotonin modulate the innate and adaptive immune responses and the inflammatory states. Several nicotinic cholinergic and serotonergic receptor subtypes have been characterized in B and T lymphocytes, monocytes, macrophages, and dendritic cells. The use of knockout mice has allowed a better characterization of nicotinic receptors and their role in anti-inflammatory processes in these cells. Cytokines play a crucial role in controlling inflammatory reactions. Nicotine and serotonin have been reported to regulate cytokine release. Cholinergic mechanisms also play an important role in inflammation through endogenous acetylcholine. Nicotine mimics this effect by activating the cholinergic anti-inflammatory pathways. New concepts of reciprocal interactions between nicotine and serotonin are emerging. The role of nicotine as an anti-inflammatory agent has been established, whereas that of serotonin remains more controversial.
Use of standardised outcome measures in adult mental health services
Authors: Slade Mike , McCrone Paul , Kuipers Elizabeth , Leese Morven , Cahill Sharon , Parabiaghi Alberto , Priebe Stefan , Thornicroft Graham
Published: November 2006

Background

Routine use of standardised outcome measures is not universal.

Aims

To evaluate the effectiveness of standardised outcome assessment.

Method

A randomised controlled trial, involving 160 representative adult mental health patients and paired staff (ISRCTN16971059). The intervention group (n=101) (a) completed monthly postal questionnaires assessing needs, quality of life, mental health problem severity and therapeutic alliance, and (b) received 3-monthly feedback. The control group (n=59) received treatment as usual.

Results

The intervention did not improve primary outcomes of patient-rated unmet need and of quality of life. Other subjective secondary outcome measures were also not improved. The intervention reduced psychiatric inpatient days (3.5 v. 16.4 mean days, bootstrapped 95% CI 1.6-25.7), and hence service use costs were £2586 (95% CI 102-5391) less for intervention-group patients. Net benefit analysis indicated that the intervention was cost-effective.

Conclusions

Routine use of outcome measures as implemented in this study did not improve subjective outcomes, but was associated with reduced psychiatric inpatient admissions.