bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Tomato Transcription Factor Pti4 Regulates Defense-Related Gene Expression via GCC Box and Non-GCC BoxcisElements[W]
Authors: Chakravarthy Suma , Tuori Robert P. , D'Ascenzo Mark D. , Fobert Pierre R. , Després Charles , Martin Gregory B. 
Published: November 2003

AbstractThe tomato transcription factor Pti4, an ethylene-responsive factor (ERF), interacts physically with the disease resistance protein Pto and binds the GCC box cis element that is present in the promoters of many pathogenesis-related (PR) genes. We reported previously that Arabidopsis plants expressing Pti4 constitutively express several GCC box–containing PR genes and show reduced disease symptoms compared with wild-type plants after inoculation with Pseudomonas syringae pv tomato or Erysiphe orontii. To gain insight into how genome-wide gene expression is affected by Pti4, we used serial analysis of gene expression (SAGE) to compare transcripts in wild-type and Pti4-expressing Arabidopsis plants. SAGE provided quantitative measurements of &gt;20,000 transcripts and identified the 50 most highly expressed genes in Arabidopsis vegetative tissues. Comparison of the profiles from wild-type and Pti4-expressing Arabidopsis plants revealed 78 differentially abundant transcripts encoding defense-related proteins, protein kinases, ribosomal proteins, transporters, and two transcription factors (TFs). Many of the genes identified were expressed differentially in wild-type Arabidopsis during infection by Pseudomonas syringae pv tomato, supporting a role for them in defense-related processes. Unexpectedly, the promoters of most Pti4-regulated genes did not have a GCC box. Chromatin immunoprecipitation experiments confirmed that Pti4 binds in vivo to promoters lacking this cis element. Potential binding sites for ERF, MYB, and GBF TFs were present in statistically significantly increased numbers in promoters regulated by Pti4. Thus, Pti4 appears to regulate gene expression directly by binding the GCC box and possibly a non-GCC box element and indirectly by either activating the expression of TF genes or interacting physically with other TFs.
Opening up Public Services to Competition by Putting Them Out to Tender: An Evaluation
Authors: Bance P. 
Published: November 2003

This article examines the effects of systematizing tendering procedures when awarding public service concessions. The opening up of the water supply industry to competition is used by way of illustration. Results show that arguments in favour of systematization are not robust when focusing solely on the expected benefits of the liberalization process. The peculiarities of the contract relationship in the delegation of public services, the mobilization of specific assets, and the long duration and incompleteness of the contracts invalidate this type of argument and expose public authorities to the opportunism of operators.The efficiency of awarding public services concessions relies on cost–benefit analysis, taking into account sectoral aspects as well as specificities of the contracting organizations and structures.The public service culture of these organizations is in this respect a key factor in the choice of efficient organizations since it conditions their ability to internalize the mission of fulfilling the public interest.
Dose‐dependent Induction of Cytochrome P450 (CYP) 3A4 and Activation of Pregnane X Receptor by Topiramate
Authors: Nallani Srikanth C. , Glauser Tracy A. , Hariparsad Niresh , Setchell Kenneth , Buckley Donna J. , Buckley Arthur R. , Desai Pankaj B. 
Published: November 2003

Summary:  Purpose: In clinical studies, topiramate (TPM) was shown to cause a dose‐dependent increase in the clearance of ethinyl estradiol. We hypothesized that this interaction results from induction of hepatic cytochrome P450 (CYP) 3A4 by TPM. Accordingly, we investigated whether TPM induces CYP3A4 in primary human hepatocytes and activates the human pregnane X receptor (hPXR), a nuclear receptor that serves as a regulator of CYP3A4 transcription. Methods: Human hepatocytes were treated for 72 h with TPM (10, 25, 50, 100, 250, and 500 μM) and known inducers, phenobarbital (PB; 2 mM), and rifampicin (10 μM). The rate of testosterone 6β‐hydroxylation by hepatocytes served as a marker for CYP3A4 activity. The CYP3A4‐specific protein and mRNA levels were determined by using Western and Northern blot analyses, respectively. The hPXR activation was assessed with cell‐based reporter gene assay. Results: Compared with controls, TPM (50–500 μM)–treated hepatocytes exhibited a considerable increase in the CYP3A4 activity (1. 6‐ to 8.2‐fold), protein levels (4.6‐ to 17.3‐fold), and mRNA levels (1.9‐ to 13.3‐fold). Comparatively, rifampicin (10 μM) effected 14.5‐, 25.3‐, and a 20.3‐fold increase in CYP3A4 activity, immunoreactive protein levels, and mRNA levels, respectively. TPM (50–500 μM) caused 1.3‐ to 3‐fold activation of the hPXR, whereas rifampicin (10 μM) caused a 6‐fold activation. Conclusions: The observed induction of CYP3A4 by TPM, especially at the higher concentrations, provides a potential mechanistic explanation of the reported increase in the ethinyl estradiol clearance by TPM. It also is suggestive of other potential interactions when high‐dose TPM therapy is used.
Gender‐specific Differences of Hypometabolism in mTLE: Implication for Cognitive Impairments
Authors: Nickel Janpeter , Jokeit Hennric , Wunderlich Gilbert , Ebner Alois , Witte Otto W. , Seitz Rüdiger J. 
Published: November 2003

Summary:  Purpose: To determine gender differences of hypometabolism and their implications for cognitive impairment in patients with medically refractory mesial temporal lobe epilepsy (mTLE). Methods: Regional cerebral glucose metabolism (rCMRGlu) was studied in 42 patients (21 male, 21 female) with either left‐ or right‐sided mTLE (22 left, 20 right) and in 12 gender‐ and age‐matched healthy controls during resting wakefulness and in 12 sex‐ and age‐matched healthy controls. Clinical characteristics were balanced across the patient subgroups. All patients were subjected to neuropsychological assessment: 41 patients had histologic changes of definite or probable hippocampal sclerosis. Results: Data analysis based on pixel‐by‐pixel comparisons and on a laterality index of regions of interest (ROIs) showed significant depressions of the mean rCMRGlu extending beyond the mesiotemporal region and temporolateral cortex to extratemporal regions including the frontoorbital and insular cortex in mTLE patients. Extramesiotemporal hypometabolism prevailed in the male patients. Metabolic asymmetry in temporal and frontal regions was related to performance in the Trail‐Making Test and WAIS‐R subitems. Conclusions: Our data showed a gender‐specific predominance of extramesiotemporal hypometabolism in male patients with mTLE related to abnormalities of temporal and frontal lobe functions.
Brain Access and Anticonvulsant Efficacy of Carbamazepine, Lamotrigine, and Felbamate in ABCC2/MRP2‐Deficient TR− Rats
Authors: Potschka Heidrun , Fedrowitz Maren , Löscher Wolfgang 
Published: November 2003

Summary:  Purpose: Different adenosine triphosphate (ATP)‐driven multidrug transporters have been described to be expressed in the luminal membrane of blood–brain barrier (BBB) endothelial cells. At this site, multidrug transporters have been suggested to restrict penetration of drugs into the brain. Increasing evidence suggests that overexpression of different multidrug transporters occurs in the region of the epileptic focus of pharmacoresistant epilepsy patients. Based on the assumption that antiepileptic drugs (AEDs) are substrates of these transporters, this overexpression may limit access of AEDs to epileptic neurons and may contribute to drug‐refractoriness. In a recent study, overexpression of multidrug resistance protein 2 (ABCC2; MRP2) was reported in BBB endothelial cells of epileptic focal tissue from pharmacoresistant patients. With brain microdialysis, we recently demonstrated that the AED phenytoin is subject to transport by ABCC2 at the BBB, whereas phenobarbital does not seem to be a substrate of ABCC2. Methods: We investigated whether ABCC2 is functionally involved in transport of the AEDs carbamazepine (CBZ), lamotrigine (LTG), and felbamate (FBM) across the BBB. The distribution of these AEDs into the brain of ABCC2‐deficient TR− rats was determined. Results: AED concentrations in plasma and brain extracellular space of these mutant rats did not differ significantly from those of rats of the corresponding background strain. In the amygdala‐kindling model of epilepsy, the anticonvulsant efficacy of LTG and FBM was comparable in both groups of rats. In contrast, CBZ exhibited a higher anticonvulsant activity in kindled ABCC2‐deficient rats as compared with nonmutant rats. Conclusions: In this present study, the microdialysis results gave no evidence that ABCC2 function modulates entry of CBZ, LTG, and FBM into the CNS of naïve rats. However, ABCC2 deficiency was associated with an increased anticonvulsant response of CBZ in the kindling model. Future investigations are planned to identify the underlying mechanism for this difference, clarifying whether a pharmacokinetic difference is detectable only when brain access of CBZ is compared in kindled ABCC2‐deficient rats and kindled nonmutant rats, which may have an increased expression of ABCC2 in response to seizures. The data substantiate that ABCC2‐deficient TR− rats are a useful tool for defining the role of ABCC2 for transport of AEDs, and give evidence that the use of kindled TR− rats may provide important supplementary information.
Involvement of Gap Junctions in the Manifestation and Control of the Duration of Seizures in Rats In Vivo
Authors: Gajda Zita , Gyengési Erika , Hermesz Edit , Ali K. Said , Szente Magdolna 
Published: November 2003

Summary:  Purpose: The possible role of gap junctions in the manifestation and control of the duration of seizures was tested on the 4‐aminopyridine–induced epilepsy model in rats in vivo, by using electrophysiologic, pharmacologic, and molecular biologic techniques. Methods: In electrophysiologic experiments, the functional states of the gap junctions were manipulated with a specific blocker (carbenoxolone) or opener (trimethylamine) at the already active focus of adult, anesthetized rats, 60 min after the induction of the first seizure, which was repeated spontaneously thereafter. Semiquantitative reverse transcriptase–polymerase chain reaction (RT‐PCR) amplification was used to measure the levels of connexin (Cx) 32, 43, and 36 messenger RNAs (mRNAs) prepared from the areas of the already active primary and mirror foci. Results: After repeated seizures, the expression levels of Cx32, Cx43, and Cx36 mRNAs at the epileptic foci were increased significantly. Blockade of the gap junctions with carbenoxolone shortened the duration of seizures and decreased the amplitude of the seizure discharges, whereas their opening with trimethylamine lengthened the duration and increased the amplitude. Secondary epileptogenesis was facilitated when the gap junctions were opened. Conclusions: Our findings support the idea that, in epileptic foci, the gap junctions are involved in the expression of rhythmic ictal discharges and in the control of the duration and propagation of the individual seizures in vivo.
Infantile Spasms in Remission May Reemerge as Intractable Epileptic Spasms
Authors: Camfield Peter , Camfield Carol , Lortie Anne , Darwish Husam 
Published: November 2003

Summary: Background:West syndrome consists of infantile spasms with hypsarrhythmia and is perceived as a disorder of infants.Methods:We describe 10 patients with West syndrome with spasms that remitted, started again, and persisted (followed up for 8–25 years).Results:In all, West syndrome developed at younger than 17 months (five cryptogenic, six symptomatic). With initial treatment, spasms completely stopped for 4.5 months to 6 years, when epileptic spasms returned. Recurrent spasms were typical with brief arm extension, eye elevation, and head drop without falling. Spasms lasted 2–6 s in rhythmic strings over 20‐ to 60‐min periods and occurred daily throughout follow‐up. Persistent spasms were particularly troublesome, because of incontinence in one and postictal confusion in several. During the string of spasms, most refused to interact, and several would wander off. Up to 15 antiepileptic drugs did not render any patient spasm free. Only two had persistent spasms as the only seizure type; six also had intractable complex partial seizures, and three had occasional grand mal convulsions. Interictal EEGs showed multifocal spikes. Ictal recordings in six showed electrodecremental events.Conclusions:Recurrent spasms after remission of West syndrome represent an extremely resistant, distressing form of epilepsy. The onset of West syndrome is age related, but it does not reliably vanish.
Diffusion Tensor MRI and Fiber Tractography of Cerebellar Atrophy in Phenytoin Users
Authors: Lee Seung‐Koo , Mori Susumu , Kim Dong Joon , Kim Sei Young , Kim Si Yeon , Chu Minkyung , Heo Kyoung , Lee Byung In , Kim Dong Ik 
Published: November 2003

Summary:  Purpose: The usefulness of diffusion tensor magnetic resonance imaging (DT‐MRI) is still in debate, and the development of clinically feasible scan protocol is encouraged. The purpose of this study was to investigate the afferent fiber system to the cerebellum in patients with phenytoin (PHT)‐induced cerebellar atrophy in comparison with cerebellar atrophy of other etiologies by using DT‐MRI. Methods: Thirteen patients (M/F ratio, 7:6; mean age, 42.5 years) and age‐matched normal controls (n = 8) participated in this study. The patient group consisted of epilepsy patients who had received PHT therapy (n = 9) and clinically diagnosed as having olivopontocerebellar atrophy (OPCA; n = 4). DT‐MRI was performed by using diffusion weighting of b = 600 s/mm2, and fractional anisotropy (FA) and color‐coded vector maps were generated. FA of the middle cerebellar peduncle (MCP), the cerebellum, and transverse pontine fibers (TPF) was measured and compared between PHT and OPCA patients. Results: Normal subjects showed FA values of 0.81 ± 0.07 in MCP, 0.69 ± 0.04 in TPF, and PHT users showed FA values of 0.84 ± 0.09 in MCP, 0.72 ± 0.08 in TPF, and 0.21 ± 0.04 in cerebellum. OPCA patients showed FA values of 0.39 ± 0.11 in MCP, 0.46 ± 0.12 in TPF, and 0.22 ± 0.07 in cerebellum. PHT users showed a statistically significant reduction of FA only in cerebellum, whereas OPCA demonstrated significant decrease of FA in MCP, TPF, and cerebellum (one‐way analysis of variance, p < 0.01). Three‐dimensional reconstruction of fiber tracts demonstrated decreased volume and altered fiber integrity within the peduncles and transverse pontine fibers in the OPCA group, whereas fiber course patterns in PHT users were similar to those in controls. Conclusions: PHT users showed normal orientation and anisotropy of MCP and TPF, whereas OPCA demonstrated impaired values, suggesting that PHT directly affects the cerebellum. DT‐MRI can demonstrate detailed fiber configurations in degenerative diseases of brainstem and cerebellum and provides insight into the pathomechanisms of cerebellar atrophy.
An Xp; Yq Translocation Causing a Novel Contiguous Gene Syndrome in Brothers with Generalized Epilepsy, Ichthyosis, and Attention Deficits
Authors: Doherty Michael J. , Glass Ian A. , Bennett Craig L. , Cotter Phil D. , Watson Nate F. , Mitchell Anna L. , Bird Tom D. , Farrell Don F. 
Published: November 2003

Summary:  Purpose: We describe two brothers with generalized epilepsy, attention deficits, congenital ichthyosis, and Leri–Weill dyschondrosteosis who harbor an unusual Xp; Yq translocation chromosome, resulting in a novel contiguous gene syndrome because of deletion of genes from the distal short arm of the X chromosome. Methods: Physical examination, neuropsychologic testing, EEG, and neuroimaging studies were performed. Because of their unusual phenotype, karyotyping, fluorescence in situ hybridization, and further molecular analyses were carried out to refine the break points of the underlying unbalanced sex chromosome rearrangement. Results: The subjects had generalized epilepsy, X‐linked ichthyosis, Madelung deformities, mesomelia, normal intelligence, and attention deficits. The brothers' karyotype was unbalanced; they inherited a maternal derivative X chromosome. Deleted distal Xp genes included short‐stature homeobox on the X chromosome (SHOX), aryl sulfatase E (ARSE), variably charged X‐chromosome mRNA gene A (VCX‐A), and steroid sulfatase (STS). The final karyotype was 46,Y,der(X)t(X; Y)(p22.3; q11.2).ish der(X) (DXZ1+, KAL+, STS‐, SHOX‐) mat. Conclusions: Loss of distal contiguous Xp genes resulted in a syndrome comprising bony deformities, ichthyosis, attention problems, and generalized epilepsy. Candidate epilepsy genes within the deleted segment, such as ASMT, a gene involved in the final synthesis of melatonin, are discussed. Cytogenetic analyses should be included in the clinical evaluation of patients with generalized epilepsy and complex phenotypes.
The Civil Servant as Legislator: Law Making in British Administration
Authors: Page Edward C. 
Published: November 2003

How are government policy commitments converted into legislation and what happens in the conversion? The role of civil servants in preparing legislation is far more important than is generally assumed. By looking at the work of four recent bill teams in Britain – teams of civil servants given the task of developing Acts of Parliament – their crucial roles in initiating policies, placing them on the political agenda (even helping secure their place in a party manifesto), developing them, making sure they pass through parliament and enacting them once they have reached the statute books are assessed. The article explores the composition and working methods of bill teams. These teams work with considerable autonomy in developing legislation, but it cannot be assumed that they operate outside ministerial control. Teams see themselves as reflecting the priorities of the government in general and their ministers in particular. Yet ministers typically know relatively little about the law they are bringing in until they receive the submissions and briefings from their officials. Perhaps the biggest danger for democracy is not a civil service putting forward proposals which a minister feels forced to accept, but rather that ministers do not notice or fully appreciate what is being proposed in their name despite having the political authority to change it and a civil service which bends over backwards to consult and accommodate them.
An Inquiry into Balanced Scorecards within Best Value Implementation in UK Local Government
Authors: Mcadam Rodney , Walker Timothy 
Published: November 2003

The aim is of this paper is to conduct an exploratory study into the use of Balanced Scorecards as an approach to implementing Best Value in UK local government. Furthermore, a participant‐observation method is used to study the development into a Balanced Scorecard within local government.There is a need to critically evaluate approaches to implementing Best Value so that local government can determine how to achieve the service performance levels laid down in the framework. There is a paucity of systematic studies exploring and critiquing the effectiveness of using the Balanced Scorecard in Best Value implementation. The paper describes an exploratory multiple case research study followed by longitudinal participant‐observer research on Balanced Scorecard development in a Best Value context. The findings show that the Balanced Scorecard can play a key role in Best Value implementation. Moreover it is also useful in linking other improvement initiatives. However, the Balanced Scorecard process must be informed by organizational and environmental information that is both accurate and adequate. The audit functions of the Business Excellence Model go some way to providing this information.
Friedman's Money Supply Rule vs. Optimal Interest Rate Policy
Authors: Evans George W. , Honkapohja Seppo 
Published: November 2003

AbstractUsing New Keynesian models, we compare Friedman's k‐percent money supply rule to optimal interest rate setting, with respect to determinacy, stability under learning and optimality. First we review the recent literature: open‐loop interest rate rules are subject to indeterminacy and instability problems, but a properly chosen expectations‐based rule yields determinacy and stability under learning, and implements optimal policy. We show that Friedman's rule also can generate equilibria that are determinate and stable under learning. However, computing the mean quadratic welfare loss, we find for calibrated models that Friedman's rule performs poorly when compared to the optimal interest rate rule.
Optimal monetary policy: is price‐level targeting the next step?
Authors: Minford Patrick , Peel David 
Published: November 2003

AbstractWe examine whether inflation targeting should be regarded as optimal. Targeting inflation implies (undesirably) that price level variance tends to infinity: we produce some evidence from both a representative agent model and a long‐used forecasting model that, once an endogenous indexation response is allowed for, price level targeting imposes no extra costs of macro variability, indeed gives significant gains.
Climbing the Staircase: science education for the knowledge economy
Authors: Geddes Roy , Stonyer Heather 
Published: November 2003

AbstractScience and technology are widely regarded as the dominant drivers of transformation to a ‘knowledge’ economy and society — a transition in which higher education has a critical role. This paper reviews the influence of successive NZ governments intention to ‘proactively steer’ the tertiary education system towards the achievement of this critical role, and describes an initiative at the Auckland University of Technology (AUT) specifically designed to meet New Zealand's needs for a well trained, articulate and flexible workforce of scientists, engineers, technicians and support staff. The ‘staircasing’ model is the culmination of an effort to adapt, modify and extend traditional models of professional science and technology education to provide a mechanism for ‘life‐long learning’ through a flexible and responsive network of purpose‐built courses.
Reading Literacy Performance in Norway: current practice and critical factors
Authors: Rasmussen Jay Beck 
Published: November 2003

AbstractThis qualitative study explored reading literacy performance of Norwegian students (Grades 1–10). Semistandardised interviews were conducted with 36 academics, school administrators, and teachers to investigate reading literacy development, factors associated with literacy performance, and recommendations for improvement. Reading literacy lessons were also observed in 10 classrooms to determine how reading literacy is developed. Data from the International Association for the Evaluation of Educational Achievement study (Elley, 1994) and the Programme for International Student Achievement study (OECD, 2001) were analysed to enrich understanding of the Norwegian literacy situation. Recommendations include greater reading education for teachers, communication and collaboration between stakeholders, engagement and interest in reading, balanced reading instruction, development of linguistic awareness, use of early intervention programmes, explicit strategy instruction, and use of bilingual education.