bluuebunny/crossref_metadata_2025 huggingface dataset:
Synthesis and Dispersion Characteristics of Multi‐Walled Carbon Nanotube Composites with Poly(methyl methacrylate) Prepared by In‐Situ Bulk Polymerization
Authors: Park Seung June , Cho Min Seong , Lim Sung Taek , Choi Hyoung Jin , Jhon Myung S.
Published: February 2004

Multi‐walled carbon nanotubes (MWNT) purified by acidic solution were processed with PMMA via an in‐situ polymerization. Experimental evidences indicate the role of radical initiator (AIBN) and MWNT, showing increases of polymerization rate and MWNT diameter. Induced radicals on the MWNT by AIBN were found to trigger the grafting of PMMA. Moreover, the solvent cast film showed a better nanoscopic dispersion of MWNT and possibilities of CNT composites in engineering applications.

Fractured surface of multi‐walled carbon nanotube composite with PMMA prepared by in‐situ bulk polymerization.

magnified image

Fractured surface of multi‐walled carbon nanotube composite with PMMA prepared by in‐situ bulk polymerization.
Focal dystonia as a presenting sign of spinocerebellar ataxia 17
Authors: Hagenah Johann M. , Zühlke Christine , Hellenbroich Yorck , Heide Wolfgang , Klein Christine
Published: February 2004

We report on the clinical manifestation of spinocerebellar ataxia 17 (SCA17) in 3 members of a German family, in whom the pathological repeat expansion in the TATA‐binding protein gene ranged from 53 to 55 repeats (normal: 29–42). The main clinical features were focal dystonia as presenting sign, followed by cerebellar ataxia, and, in the later course of one case, dementia and marked spasticity with signs of cerebellar and cerebral atrophy on brain computed tomography (CT) scan. In conclusion, SCA17 mutations should be considered in the differential diagnosis of focal dystonia. © 2003 Movement Disorder Society
Hyperhomocysteinaemia in treated patients with Huntington's disease homocysteine in HD
Authors: Andrich Jürgen , Saft Carsten , Arz Anneliese , Schneider Birgit , Agelink Markus W. , Kraus Peter H. , Kuhn Wilfried , Müller Thomas
Published: February 2004

Significantly increased plasma total homocysteine levels (t‐Hcys) appeared in treated Huntington disease (HD) patients compared to controls and untreated HD subjects. Because the protein Huntingtin interacts with the homocysteine metabolism modulating enzyme cystathionine β‐synthase, we hypothesize that homocysteine promotes neurodegeneration in HD. © 2003 Movement Disorder Society
Reply: Cerebrospinal fluid Aβ42 levels in multiple system atrophy
Authors: Holmberg Bjorn
Published: February 2004

The letter to which this article refers can be found online: Mov Disord 2004;19(2):238–240.
Differential expression of cell cycle regulatory molecules and evidence for a “cyclin switch” during progression of prostate cancer
Authors: Maddison Lisette A. , Huss Wendy J. , Barrios Roberto M. , Greenberg Norman M.
Published: February 2004

BACKGROUND

Deregulation of the cell cycle can be viewed as both cause and consequence of cancer. Cyclin expression regulates progression through the cell cycle and although some cyclins have been examined in prostate cancer, the spatial and temporal changes in expression of these molecules during progression of autochthonous disease has not been fully explored.

METHODS

Expression patterns of cyclins and cyclin dependent kinases during the different stages of progression in the spontaneous autochthonous TRAMP model were examined by RNAse protection assay, Western blot analysis, and immunohistochemistry.

RESULTS

Differential expression of cell cycle regulatory molecules was observed during prostate cancer progression. Levels of the D‐type cyclins decreased during progression while expression of cyclin E increased both at the mRNA and protein levels. The level of cyclin A and cyclin B expression increased beginning in early stage tumors and continued to increase throughout progression. The levels of cyclin dependent kinases did not change substantially during progression of the TRAMP model.

CONCLUSIONS

The spatial and temporal pattern of mitotic cyclin expression during prostate cancer progression suggests that these molecules represent potential therapeutic targets. The differential expression of D‐type cyclins may have implications with respect to androgen receptor mediated gene expression. © 2003 Wiley‐Liss, Inc.
A Prospective longitudinal study comparing the impact of external radiation therapy with radical prostatectomy on health related quality of life (HRQOL) in prostate cancer patients
Authors: van Andel G. , Visser A.P. , Zwinderman A.H. , Hulshof M.C.C.M. , Horenblas S. , Kurth K.H.
Published: February 2004

BACKGROUND

The objective of the present study is to compare the impact on the general and disease‐specific health related quality of life (HRQOL) of external radiation therapy (ERT) with radical prostatectomy (RP) in patients with localized prostate cancer, and to explore which factors, and to what extent, contribute to the assessed changes in HRQOL.

METHODS

One hundred and thirty eight patients participated in this prospective longitudinal study. They completed before treatment (T0) and after 12 months (T1) a questionnaire constructed of validated instruments, measuring HRQOL and several psychosocial factors (PF). Among other things, multiple regression analyses including all baseline characteristics, HRQOL and PF were executed in order to meet the objectives.

RESULTS

RP patients showed significantly more improvement in their emotional function, while they reported more incontinence and a worse sexual function. There was significantly more improvement in the overall HRQOL of ERT patients, while the changes in the gastrointestinal function of these patients were significantly worse. Only the differences with respect to incontinence can be attributed to the treatment itself. Almost all HRQOL change scores are primarily influenced by their own baseline score. The influence of other factors, like age, socioeconomic status, and several PF, is limited.

CONCLUSIONS

The impact on HRQOL of ERT is similar to that of RP, except for incontinence. RP patients suffer more from incontinence than ERT patients. Changes in the assessed HRQOL are mainly influenced by the pre‐treatment HRQOL scores. © 2003 Wiley‐Liss, Inc.
Differential expression of hZnT‐4 in Human prostate tissues
Authors: Beck Frances W.J. , Prasad Ananda S. , Butler Charles E. , Sakr Wael A. , Kucuk Omer , Sarkar Fazlul H.
Published: February 2004

BACKGROUND

Altered zinc levels in prostate benign prostatic hyperplasia (BPH) and carcinoma is well documented. It is not known whether loss of zinc, necessary to restrain aggressive growth, results from loss of a single specific or multiple zinc transporters.

METHODS

Human prostate tissues from patients who underwent radical prostatectomy were screened by RT‐PCR analysis for five zinc transporters. Relative cDNA expression was determined in normal, BPH, and tumor specimens and four prostate epithelial cell lines.

RESULTS

Surgical specimens were obtained from patients with assigned Gleason scores ranging from 5 to 9. Relative expression of hZIP‐1 and hZnT‐1 were prominent in most samples with relatively lesser degree of expression of hZIP‐2 and no detectable expression of hZnT‐3. Expression of hZnT‐4 was decreased in BPH and tumor samples compared to normal tissue.

CONCLUSIONS

These data suggest that zinc homeostasis in normal prostate tissues results from an interplay of multiple transporters and decreased hZnT‐4 expression is associated with prostate tissue abnormalities independent of total cellular zinc content. © 2003 Wiley‐Liss, Inc.
Metabolic susceptibility genes and prostate cancer risk in a southern European population: The role of glutathione S‐transferases GSTM1, GSTM3, and GSTT1 genetic polymorphisms
Authors: Medeiros Rui , Vasconcelos André , Costa Sandra , Pinto Daniela , Ferreira Paula , Lobo Francisco , Morais António , Oliveira Jorge , Lopes Carlos
Published: February 2004

BACKGROUND

Glutathione S‐transferase (GST) metabolic enzymes may be involved in the development of human cancer. Genetic polymorphisms have been reported in GSTM1, GSTM3, and GSTT1 with functional alterations and influencing cancer risk.

METHODS

We analyzed DNA samples from 335 (670 alleles) unrelated individuals, 185 community control subjects, and 150 prostate cancer (PC) patients, for GSTM1, GSTM3, and GSTT1 genotypes using polymerase chain reaction (PCR).

RESULTS

The analysis of the frequencies from the 670 alleles indicates that men carrying two B‐alleles (GSTM3) have increased risk for PC (OR = 5.50, 95% confidence interval (CI) 1.2–25.8; P = 0.016). Multivariate logistic regression analysis confirmed this association (OR = 5.2, 95% CI 1.1–25.0; P = 0.036). No increased PC risk was observed for men carrying any of the GSTM1 or GSTT1 genotypes (OR = 1.20, 95% CI 0.75–1.90; P = 0.420 for GSTM1 null and OR = 0.87, 95% CI 0.50–1.51; P = 0.550 for GSTM1 null). However, GSTT1 null was overrepresented in men with advanced PC disease (P = 0.038).

CONCLUSIONS

Our results indicate that polymorphism in the GSTM3 may be an important biomarker for PC risk, especially in the definition of the genetic risk profile of populations of southern Europe. © 2003 Wiley‐Liss, Inc.
Intraosseous growth of human prostate cancer in implanted adult human bone: Relationship of prostate cancer cells to osteoclasts in osteoblastic metastatic lesions
Authors: Yonou Hiroyuki , Ochiai Atsushi , Goya Masato , Kanomata Naoki , Hokama Sanehiro , Morozumi Makoto , Sugaya Kimio , Hatano Tadashi , Ogawa Yoshihide
Published: February 2004

BACKGROUND

More than 80% of patients with advanced prostate cancer have skeletal involvement, but the biology of bone metastasis is poorly understood. This study investigated the in vivo formation and progression of bone metastases under conditions that resembled the human bone environment as closely as possible.

METHODS

Adult human bone fragments were implanted subcutaneously into 120 male NOD/SCID mice. Four weeks later, 1 × 107 LNCaP prostate cancer cells or phosphate‐buffered saline were injected intravenously into 80 or 40 mice, respectively. The implanted bone fragments were removed from 20 to 10 mice in each group at 2, 4, 6, and 8 weeks after injection.

RESULTS

LNCaP colonized the bone marrow blood vessels within 2 weeks, and then gradually expanded into the entire medullary cavity. An osteoblastic response often occurred at the edges of metastatic foci (intertrabecular bone metaplasia). In addition, new bone formation was observed adjacent to mature lamellar bone (appositional bone formation). These two processes appeared to occur through different mechanisms, but might similarly cause osteosclerosis. Osteoclasts showed a marked increase in numbers at sites of early tumor invasion, whereas few osteoclasts were observed at sites where tumor invasion was complete.

CONCLUSIONS

The predominance of osteoblastic change with resorption may lead to bone remodeling in metastatic lesions, and osteoclasts may play an important role in bone metastasis from prostate cancer. © 2003 Wiley‐Liss, Inc.
The ceramide analog, B13, induces apoptosis in prostate cancer cell lines and inhibits tumor growth in prostate cancer xenografts
Authors: Samsel Leigh , Zaidel Grazyna , Drumgoole Honesty M. , Jelovac Danijela , Drachenberg Cinthia , Rhee Juong G. , Brodie Angela M.H. , Bielawska Alicja , Smyth Miriam J.
Published: February 2004

BACKGROUND

Apoptosis is a therapeutic target for the elimination of cancer cells. As elevations in ceramide levels induce apoptosis, there is much excitement about the use of agents that elevate ceramide levels as novel chemotherapeutic agents. Ceramidases are enzymes involved in degradation of ceramide and inhibition of ceramidase has been proposed as a mechanism to increase ceramide levels. This study provides the first insight into the effect of B13, an inhibitor of acid ceramidase, on human prostate cancer cell lines and xenografts.

METHODS

Cell death was evaluated by the trypan blue assay; apoptosis by the Apo2.7 apoptosis assay; and glutathione levels by HPLC. Tumors were irradiated with a dose of 5 Gy of X‐rays (250 kVp, 15 mA, 2 Gy/min) and tumor volume was measured during the course of the experiment. At the conclusion of the experiment, tumor weight was determined and the tumors were evaluated histologically.

RESULTS

B13 is an inducer of cell death, by apoptosis, in cultured prostate cancer cells. LNCaP and PC3 cells have different responsiveness to the enantiomers of B13. In LNCaP cells, the R enantiomer of B13 (10 μM) was significantly more effective than the S enantiomer at inducing cell death as determined by the trypan blue assay, culminating in approximately 90% cell death at 48 hr. In contrast, the same concentration of B13S induced <20% cell death at 48 hr. In PC3 cells, the S enantiomer was a more effective inducer of cell death, culminating in ∼30% cell death, relative to 14% for B13R in this model. Evaluation of induction of apoptosis by the Apo2.7 mitochondrial assay confirmed that this induction of cell death was by apoptosis. Concurrent with induction of apoptosis, glutathione levels drop in response to B13. Specifically, B13R caused a significant drop in glutathione levels in LNCaP cells, culminating in a reduction to 40% control values at 48 hr. In PC3 cells, in contrast, the drop in glutathione levels was more dramatic, culminating in a drop to 12% control values in response to B13S at 48 hr. The effects of B13R, however, were not significantly different from control values. In in vivo studies using a model of xenografted androgen‐insensitive prostate cancer, B13 sensitized the tumors to the effects of radiation, resulting in a significant reduction in tumor volume and weight after treatment with the combination of B13 and radiation. Microscopic evaluation of the tumors indicated that apoptosis was the primary mechanism of this effect.

CONCLUSIONS

Targeting ceramide pathways may be a novel treatment strategy for hormone refractory prostate cancer. © 2004 Wiley‐Liss, Inc.
Standard operating procedures for clinical research personnel – Part 19
Authors: Bohaychuk Wendy , C.D. Graham Ball
Published: February 2004

This is the nineteenth in a series of articles containing proposals for wording and content of standard operating procedures (SOPs) for clinical research activities conducted by sponsors and Contract Research Organisations (CROs). The procedures include those required by the International Conference on Harmonisation (ICH), the Food and Drug Administration (FDA), many other guidelines and regulations, and ‘best practice’ observed by the authors. The model forms require modification for actual use. In this article, SOPs are presented for management of study medications/devices and randomisation procedures: final disposition of study medications/devices (SOP 508); recall of investigational products (SOP 509); reallocation of investigational products between study sites (SOP 510); requesting and preparing randomisation schedules (SOP 511); revealing randomisation code assignments during studies (SOP 512) and revealing randomisation code assignments after study completion (SOP 513). (The full text of all 101 SOPs is available from the authors.) Copyright © 2004 John Wiley & Sons, Ltd.
Start up: CQA
Authors: Winchell Terry
Published: February 2004

The current article is focused on the start up, design, and operation of a new clinical quality assurance unit or the restructuring of an existing one, and is intended to provide a management overview. General information is provided on appropriate company structure, leadership, staffing & evaluations, operations, standard operating procedures, useful information technology tools, as well as a general approach to compliance. References serve to provide additional details on many of these topics. Copyright © 2004 John Wiley & Sons, Ltd.
Why clinical trials fail before they get even started: the ‘frontloading’ process
Authors: Beck Jürgen , Esser Peter J. , Herschel Michael B.
Published: February 2004

Whether a clinical trial will meet its timelines is often determined during its recruitment phase. How clinical trials should be run only becomes an issue once they are initiated. But it is during the preparatory phase, between the point when a Go‐decision is made to when the first site is initiated, when it is often decided whether a trial will meet the timelines required. Failure can be expected if ‘frontloading’, the process required to meet the objective, is not carried out properly.

Successful frontloading depends on a detailed communication plan with appropriate team‐building, training, standardized communication and behaviour concepts; an action plan with precise details of what needs to be done during specific scenarios; and electronic trial‐specific action and communication tools that ensure swift action when needed. Team building and training on standardized communication procedures are especially important. Detailed reporting (beyond the purely technical pre‐study visit reports); efficient use of early alert tools that identify risks; and prevention tools that avoid deviations from the plan before they actually occur, all play an important role as well. The components of the preparatory phase as well as its most common shortcomings as experienced from trouble‐shooting actions taken to save endangered clinical trails will be outlined. The frontloading process will be reviewed both from the perspectives of the industry and the trouble‐shooting crisis manager. Special emphasis will be put on legal aspects. Copyright © 2004 John Wiley & Sons, Ltd.
What's new?
Authors: Hattemer‐Apostel Rita , Broughton Steve
Published: February 2004

The What's New? section in the Quality Assurance Journal aims to draw attention to items of importance to QA professionals. There is usually a three‐month interval between final submission of manuscripts and distribution of the journal. For this issue, the entries in the What's New? section arise from the period of 01 September 2003 to 30 November 2003. If you feel that there is any other new information that should be brought to the attention of readers, please let us know by e‐mailing: rha@verdandi.ch. Copyright © 2004 John Wiley & Sons, Ltd.
Reverse engineering Web applications: the WARE approach
Authors: Di Lucca Giuseppe Antonio , Fasolino Anna Rita , Tramontana Porfirio
Published: February 2004

The rapid, progressive diffusion of Web applications in several productive contexts of our modern society is laying the foundations of a renewed scenario of software development, where one of the emerging problems is that of defining and validating cost‐effective approaches for maintaining and evolving these software systems.

Due to several factors, the solution to this problem is not straightforward. The heterogeneous and dynamic nature of components making up a Web application, the lack of effective programming mechanisms for implementing basic software engineering principles in it, and undisciplined development processes induced by the high pressure of a very short time‐to‐market, make Web application maintenance a challenging problem. A relevant issue consists of reusing the methodological and technological experience in the sector of traditional software maintenance, and exploring the opportunity of using reverse engineering to support effective Web application maintenance.

This paper presents an approach for defining reverse engineering processes involving Web applications. The approach has been used to implement a process, including reverse engineering methods and a supporting software tool, that helps to understand existing undocumented Web applications to be maintained or evolved, through the reconstruction of UML diagrams. The proposed reverse engineering process has been submitted to a validation experiment, the results of which showed the usability of the process for reverse engineering Web applications with different characteristics, and highlighted possible areas for improvement of its effectiveness. The experiment and the lessons learned from it are presented in the paper. Copyright © 2004 John Wiley & Sons, Ltd.
Modelling the evolution of legacy systems to Web‐based systems
Authors: Lavery Janet , Boldyreff Cornelia , Ling Bin , Allison Colin
Published: February 2004

To advance operational legacy systems, with their out‐of‐date software, distributed data and entrenched business processes, to systems that can take advantage of current Web technologies to give consistent, customized and secure access to existing information bases and legacy systems is a complex and daunting task. The Institutionally Secure Integrated Data Environment (INSIDE) is a collaborative project between the Universities of St Andrews and Durham that is addressing the issues surrounding the development and delivery of integrated systems for large institutions, constrained by the requirement of working with the existing information bases and legacy systems. The work has included an exploration of the incremental evolution of existing systems by building Web‐based value‐added services upon foundations derived from analysing and modelling the existing legacy systems. Progressing from initial informal models to more formal domain and requirements models in a systematic way, following a meta‐process incorporating good practice from domain analysis and requirements engineering has allowed the project to lay the foundation for its development of Web‐based services. Copyright © 2004 John Wiley & Sons, Ltd.
Statistical testing of Web applications
Authors: Tonella Paolo , Ricca Filippo
Published: February 2004

The World Wide Web, initially intended as a way to publish static hypertexts on the Internet, is moving toward complex applications. Static Web sites are being gradually replaced by dynamic sites, where information is stored in databases and non‐trivial computation is performed.

In such a scenario, ensuring the quality of a Web application from the user's perspective is crucial. Techniques are being investigated for the analysis and testing of Web applications for such a purpose. However, a static analysis of the source code may be extremely difficult (and, in general, infeasible) because of the presence of dynamic generation of the HTML code that is part of the application under analysis.

In this paper, a dynamic analysis technique is proposed for the extraction of a Web application model through its execution. Availability of statistical data about the accesses to the pages generated by the Web application is exploited for statistical testing, based on the recovered model. Test cases can be prioritized, so as to exercise the most frequently followed paths first. Moreover, statistical reproduction of the user's navigation paths allows for an estimation of the reliability of the application. Copyright © 2004 John Wiley & Sons, Ltd.
Migrating to Web services: a performance engineering approach
Authors: Litoiu Marin
Published: February 2004

In this paper we look at several performance pitfalls that Web services are facing today and at the performance penalties that have to be paid when exposing a legacy application as a Web service. We investigate two performance metrics of Web services, latency and scalability, and compare them with those of legacy middleware. The goal of the paper is to show how the performance penalties can be mitigated by following the principles and methods of performance engineering. Performance models can help the migration decisions, especially when new architectures or new deployment topologies are sought. The paper shows the mechanisms of building and solving a performance model involving Web services. An example is presented throughout the paper. Copyright © 2004 John Wiley & Sons, Ltd.
Analysis of Web‐usage behavior for focused Web sites: a case study
Authors: El‐Ramly Mohammad , Stroulia Eleni
Published: February 2004

The number of Web users and the diversity of their interests increase continuously; Web‐content providers seek to infer these interests and to adapt their Web sites to improve accessibility of the offered content. Usage‐pattern mining is a promising approach in support of this goal. Assuming that past navigation behavior is an indicator of the users' interests, then, Web‐server logs can be mined to infer what the users are interested in. On that basis, the Web site may be reorganized to make the interesting content more easily accessible or recommendations can be dynamically generated to help new visitors find information of interest faster. In this paper, we discuss a case study examining the effectiveness of sequential‐pattern mining for understanding the users' navigation behavior in focused Web sites. This study examines the Web site of an undergraduate course, as an example of a focused Web site that offers information intrinsically related to a process and closely reflects the workflow of this underlying process. We found that in such focused sites, indeed, visitor behavior reflects the process supported by the Web site and that sequential‐pattern mining can effectively predict Web‐usage behavior in these sites. Copyright © 2004 John Wiley & Sons, Ltd.
Four permeases import proline and the toxic proline analogue azetidine‐2‐carboxylate into yeast
Authors: Andréasson Claes , Neve Etienne P. A. , Ljungdahl Per O.
Published: February 2004

We have found that proline and the toxic proline analogue azetidine‐2‐carboxylate (AzC) are efficiently imported into Saccharomyces cerevisiae cells by four amino acid permeases, including two nitrogen‐regulated permeases (PUT4 and GAP1) and two permeases that are regulated by the SPS sensor of extracellular amino acids (AGP1 and GNP1). In contrast to Agp1p, Gnp1p is not functionally expressed when cells are grown on media containing proline as sole nitrogen source. These findings have implications for the interpretation of studies using AzC to characterize nitrogen source‐dependent regulation of amino acid uptake and of post‐Golgi targeting and localization of amino acid permeases in yeast. Copyright © 2004 John Wiley & Sons, Ltd.
Cloning and expression analysis of the ornithine decarboxylase gene (PbrODC) of the pathogenic fungus Paracoccidioides brasiliensis
Authors: Niño‐Vega Gustavo A. , Sorais Françoise , Calcagno Ana‐María , Ruiz‐Herrera José , Martínez‐Espinoza Alfredo D. , San‐Blas Gioconda
Published: February 2004

We describe the isolation and sequencing of PbrODC, the gene encoding ornithine decarboxylase (ODC) in Paracoccidioides brasiliensis. The gene contains a single open reading frame made of 1413 bp with a single intron (72 bp), and encodes a 447 amino acid polypeptide with a predicted molecular weight of 50.0 kDa, an isoelectric point of 4.9 and a high similarity to other fungal ornithine decarboxylases. Functionality of the gene was demonstrated by transformation into a Saccharomyces cerevisiae odc null mutant. A phylogenetic tree generated with several fungal ODCs provided additional evidence to favour a taxonomic position for P. brasiliensis as an ascomycetous fungus, belonging to the order Onygenales. Expression of the PbrODC gene was determined by Northern analyses during growth of the mycelial and yeast forms, and through the temperature‐regulated dimorphic transition between these two extreme phases. Expression of PbrODC remained constant at all stages of the fungal growth, and did not correlate with a previously observed increase in the activity of ornithine decarboxylase at the onset of the budding process in both yeast growth and mycelium‐to‐yeast transition. Accordingly, post‐transcriptional regulation for the product of PbrODC is suggested. The PbrODC gene sequence is available at the GenBank database under Accession No. AF212867. Copyright © 2004 John Wiley & Sons, Ltd.
SRE1 and SRE2 are two specific steroid‐responsive modules of Candida drug resistance gene 1 (CDR1) promoter
Authors: Karnani Neerja , Gaur Naseem Akhtar , Jha Sudhakar , Puri Neeti , Krishnamurthy Shankarling , Goswami Shyamal K. , Mukhopadhyay Gauranga , Prasad Rajendra
Published: February 2004

CDR1 gene encoding an ATP‐driven drug extrusion pump has been implicated in the development of azole‐resistance in Candida albicans. Although the upregulation of CDR1 expression by various environmental factors has been documented, the molecular mechanism underlying such process is poorly understood. We have demonstrated earlier that the CDR1 promoter encompasses a large number of cis‐regulatory elements, presumably mediating its response to various drugs. In this study we have identified a novel steroid responsive region (SRR) conferring β‐oestradiol and progesterone inducibility on the CDR1 promoter. The SRR is located −696 to −521 bp upstream of the transcription start site; it is modular in nature and can confer steroid responsiveness to a heterologous promoter (ADH1) linked to a GFP reporter gene. In vitro DNase I protection analyses of SRR revealed two progesterone responsive sequences (−628 to −594 and −683 to −648) and one β‐oestradiol responsive sequence (−628 to −577), which was further corroborated by the gel mobility shift assay. Deletion analyses within the SRR further delimited these steroid responsive sequences into two distinct elements, viz. SRE1 and SRE2. While SRE1 (−677 to −648) responds only to progesterone, SRE2 (−628 to −598) responded to both progesterone and β‐oestradiol. Both SRE1 and SRE2 were specific for steroids, as they did not respond to other drugs, such as cycloheximide, miconazole and terbinafine. In silico comparison of the SRE1/2 with the promoter sequences of other MDR (CDR2 and PDR5) and non‐MDR (HSP90) steroid‐responsive genes revealed a similarity with respect to conservation of three 5 bp stretches (AAGAA, CCGAA and ATTGG). Taken together, we have identified a novel steroid responsive cis‐regulatory sequence in the CDR1 promoter, which presumably can be instrumental in understanding the steroid response cascade in Candida albicans. Copyright © 2004 John Wiley & Sons, Ltd.
Experiments on the discrimination of fish and seabed echoes
Authors: MacLennan D.N. , Copland P.J. , Armstrong E. , Simmonds E.J.
Published: February 2004

During acoustic surveys for biomass estimation, fish aggregations near the seabed may not be correctly measured due to false detection of the bottom echo. The extent of this problem depends on the spatial and density features of the near-seabed aggregations. We conducted experiments using a tower structure deployed close to the bottom of a sea loch. The tower is 10 m high with a split-beam transducer at the top and a fish cage at the bottom. The effect of a bottom slope is simulated by tilting the transducer. In experiments with various densities and sizes of gadoids in the cage, echoes from the vicinity of the seabed were studied over hard and soft ground. In addition to the range, the split-beam echosounder gives two angular coordinates of the target direction. These may be combined into one measure of angular displacement, namely, the angle between the apparent target direction and the transducer axis. We call this the split-beam angle (SBA). We found that the SBA is not necessarily an accurate indication of the target direction. Echoes from fish aggregations and the seabed have different characteristics in this respect. When the seabed echo is detected with few interfering targets above, the SBA is an accurate indication of the seabed slope, and assuming the slope does not change over a short series of pings, the SBA is highly correlated. On the other hand, the SBA from multiple fish echoes is highly variable, as expected, and the ping-to-ping variation is essentially random. Furthermore, when the seabed echo is transmitted through a substantial density of fish, the interference can change the SBA, although the ping-to-ping correlation of the seabed SBA remains superior to that of fish aggregations. We also studied records from acoustic surveys on various research vessels to provide comparable results at full scale. When there is a low density of near-seabed fish, the correlation between the fore-aft SBA and the seabed gradient is optimal at the start of the first seabed echo; it declines at sub-bottom ranges. When there are dense aggregations of fish near the seabed, the automatic bottom-detection algorithm may be located on top of the aggregation, so that the echo integration misses a substantial quantity of fish. Examples from acoustic surveys in the North Sea are presented to illustrate this problem.
A Randomized Controlled Trial of Knifelight and Open Carpal Tunnel Release
Authors: BHATTACHARYA R. , BIRDSALL P.D. , FINN P. , STOTHARD J.
Published: February 2004

A randomized controlled trial was done to compare the results of carpal tunnel decompression using the standard open approach and the Knifelight® technique. Twenty-six patients with bilateral carpal tunnel syndrome requiring operation were selected for the study and the operative technique was randomized for the first hand. Six weeks later, the second hand was operated upon using the alternate technique. There was little difference between the two techniques with regard to time taken to return to work, return of grip strength, symptom relief, complications, incidence of pillar pain and patient preference. However, the incidence of scar tenderness was significantly lower with the Knifelight® technique.
MEK inhibition impairs influenza B virus propagation without emergence of resistant variants
Authors: Ludwig Stephan , Wolff Thorsten , Ehrhardt Christina , Wurzer Walter Jürgen , Reinhardt Jens , Planz Oliver , Pleschka Stephan
Published: February 2004

Influenza A and B viruses are still a major worldwide threat. We demonstrate that influenza B virus infection induces signaling via the Raf/MEK/ERK cascade, a process required for efficient virus production. Expression of dominant‐negative Raf and ERK mutants or treatment with a MEK inhibitor (U0126) strongly impaired viral propagation, while selective activation of the pathway resulted in increased virus titers. MEK inhibition appears to interfere with a distinct viral nuclear export process. Most importantly, no resistant virus variants emerged in the presence of U0126 demonstrating that influenza viruses cannot easily adapt to the missing cellular function.
The interplay between classical and alternative isoprenoid biosynthesis controls γδ T cell bioactivity of Listeria monocytogenes
Authors: Begley Máire , Gahan Cormac G.M. , Kollas Ann-Kristin , Hintz Martin , Hill Colin , Jomaa Hassan , Eberl Matthias
Published: February 2004

Isoprenoids are synthesised either through the classical, mevalonate pathway, or the alternative, non‐mevalonate, 2‐C‐methyl‐D‐erythritol 4‐phosphate (MEP) pathway. The latter is found in many microbial pathogens and proceeds via (E)‐4‐hydroxy‐3‐methyl‐but‐2‐enyl pyrophosphate (HMB‐PP), a potent activator of human Vγ9/Vδ2 T cells. Listeria monocytogenes is the only pathogenic bacterium known to contain both pathways concurrently. Strategic gene knockouts demonstrate that either pathway is functional but dispensable for viability. Yet, disrupting the mevalonate pathway results in a complementary upregulation of the MEP pathway. Vγ9/Vδ2 T cell bioactivity is increased in ΔlytB mutants where HMB‐PP accumulation is expected, and lost in ΔgcpE mutants which fail to produce HMB‐PP.
Sepoys, Convicts and the ‘Bazaar’ Contingent: The Emergence and Exclusion of ‘Hindustani’ Pioneers at the Singapore Frontier
Authors: Rai Rajesh
Published: February 2004

The article studies migrants from Uttar Pradesh in Singapore who have historically identified themselves as ‘Hindustani’ – a group that has largely been ignored in historical literature of the Indian diaspora in Singapore. Through an examination of British expansion in India in the early nineteenth century, parallel developments in Southeast Asia, community publications and oral testimonies, the article attempts to ‘(re)discover’ the history of Hindustani migration in Singapore.
Kept in Position: The Labour Front–Alliance Government of Chief Minister David Marshall in Singapore, April 1955 – June 1956
Authors: Low James
Published: February 2004

Using declassified British documents and Chinese-language newspapers, this paper seeks to supplement existing understanding of Chief Minister David Marshall's Labour Front-Alliance Government in Singapore from April 1955 to June 1956. From the outset, the government's reforms were hampered by its own weaknesses. It was viable only because British policy was to keep it ‘in position’.
History and the Imaginaries of ‘Big Singapore’: Positioning the Sun Yat Sen Nanyang Memorial Hall
Authors: Jianli Huang , Lysa Hong
Published: February 2004

The establishment of the Sun Yat Sen Nanyang Memorial Hall marks the PAP government's charting of a revolutionary, modernising genealogy of seismic proportions for the fashioning of a ‘Big Singapore’ as the political, economic and cultural focus of the Chinese diaspora. Such effort in reorienting history is problematic and the ethnicisation of national identity is contested, not least by Singapore's Chinese-language intellectuals.
Men, Masculinities and Symbolic Violence in Recent Indonesian Cinema
Authors: Clark Marshall
Published: February 2004

This article investigates images of men and masculinities in post-New Order Indonesian popular culture, focusing on a recent and path-breaking Indonesian film, Kuldesak. The theoretical sociology of Pierre Bourdieu is utilised to suggest that if Indonesian women are to be assisted in their efforts to resist the gender inequality of Indonesia's patriarchal gender regime, then the social gendering of men and masculinity must also be understood.
The Sulu Zone Revisited
Authors: Sutherland Heather
Published: February 2004

Iranun and Balangingi. Globalization, maritime raiding and the birth of ethnicity
By JAMES FRANCIS WARREN
Singapore: Singapore University Press, 2002. Pp. xxii, 585. Maps, Figures, Tables,
Notes, Bibliography, Index.

James Warren's rewarding Iranun and Balangingi (2002) expands on his classic The Sulu Zone (1981) but retains the explanatory model: Southern Philippine slave-raiding (1768–1898) was caused by the capitalist world economy's demand for commodities. This essay suggests that Warren's depiction of servility is too undifferentiated, that he may have overestimated labour needs and elite control while underestimating free trade.
On the Parallel Between Mathematics and Morals
Authors: Franklin James
Published: February 2004

The imperviousness of mathematical truth to anti-objectivist attacks has always heartened those who defend objectivism in other areas, such as ethics. It is argued that the parallel between mathematics and ethics is close and does support objectivist theories of ethics. The parallel depends on the foundational role of equality in both disciplines. Despite obvious differences in their subject matter, mathematics and ethics share a status as pure forms of knowledge, distinct from empirical sciences. A pure understanding of principles is possible because of the simplicity of the notion of equality, despite the different origins of our understanding of equality of objects in general and of the equality of the ethical worth of persons.
The possibility of a free-will defence for the problem of natural evil
Authors: MAWSON T. J.
Published: February 2004

In this paper, I consider various arguments to the effect that natural evils are necessary for there to be created agents with free will of the sort that the traditional free-will defence for the problem of moral evil suggests we enjoy – arguments based on the idea that evil-doing requires the doer to use natural means in their agency. I conclude that, despite prima facie plausibility, these arguments do not, in fact, work. I provide my own argument for there being no possible world in which creatures enjoying this sort of freedom exist yet suffer no natural evil, and conclude that the way is thus open for extending the free-will defence to the problem of natural evil.
Pantheism and current ontology
Authors: STEINHART ERIC
Published: February 2004

Pantheism claims: (1) there exists an all-inclusive unity; and (2) that unity is divine. I review three current and scientifically viable ontologies to see how pantheism can be developed in each. They are: (1) materialism; (2) Platonism; and (3) class-theoretic Pythagoreanism. I show how each ontology has an all-inclusive unity. I check the degree to which that unity is: eternal, infinite, complex, necessary, plentiful, self-representative, holy. I show how each ontology solves the problem of evil (its theodicy) and provides for salvation (its soteriology). I conclude that Platonism and Pythagoreanism have the most divine all-inclusive unities. They support sophisticated contemporary pantheisms.
The very idea of design: what God couldn't do
Authors: KORTUM RICHARD D.
Published: February 2004

This paper argues for the proposition that there is fundamental incoherence in the idea of a divine designer. Such a being would have to have intentions and thoughts prior to designing and making a world. But it is a necessary truth that thought – of the complex and articulated kind necessary for the design of a cosmos – presupposes possession of language. It is further necessarily true that language is impossible, save for beings who inhabit a public world containing other linguistic subjects. The divine designer would be the impossible exemplar of the private language, whose incoherence was demonstrated by Wittgenstein. Objections to this line of argument are noted and rebutted.

Even God can't whisper in His own ear.Isaak Babel
Ideal worlds and the transworld untrustworthy
Authors: ALMEIDA MICHAEL J.
Published: February 2004

The celebrated free-will defence was designed to show that the ideal-world thesis presents no challenge to theism. The ideal-world thesis states that, in any world in which God exists, He can actualize a world containing moral good and no moral evil. I consider an intriguing two-stage argument that Michael Bergmann advances for the free-will defence, and show that the argument provides atheologians with no reason to abandon the ideal-world thesis. I show next that the existence of worlds in which every essence is transworld untrustworthy provides atheologians with no better reason to abandon the ideal-world thesis. I conclude that neither the free-will defence nor Bergmann's revised free-will defence is a convincing response to the atheological challenge.
‘Dishonourable’ youth, guilds, and the changed world view of sex, illegitimacy, and women in late-sixteenth-century Germany
Authors: BOES MARIA R.
Published: February 2004

This study focuses on two closely related exclusionary guild policies implemented in Germany towards the latter part of the sixteenth century: the barring of illegitimates and women. The article addresses the reasons for and, more importantly, the repercussions of these exclusions, which affected many cultural and mentality patterns and led to the social and psychological scarring of illegitimates and their unwed mothers for centuries to come.
Networks among Bretons? The evidence for Paris, 1875–1925
Authors: MOCH LESLIE PAGE
Published: February 2004

This article questions the notion that migrant networks provided an incentive to travel by furnishing both contacts upon arrival and continued assistance for those who remained. It focuses on newcomers to Paris from Brittany from 1875 to 1925. Sources include (a) memoirs and interview data from large-scale studies, (b) information on marriage patterns in the XIVe arrondissement and the industrial suburb of Saint-Denis, and (c) information on the witnesses to these marriages. Although each source reveals a different configuration of contacts, together they suggest the importance of ongoing family ties and significant contacts formed from ‘weak ties’ after arrival.
Counting death and disease: classification of death and disease in the interwar years, 1919–1939
Authors: BOROWY IRIS
Published: February 2004

The International Lists of Causes of Death and Diseases underwent their Fourth and Fifth Revisions during the years before the First and Second World Wars, the only time that two institutions of different disciplines, the International Statistical Institute and the League of Nations Health Organization, participated in the revision process. This resulted in a mixture of institutional rivalry and cooperation, involving national, ideological and professional interests.

The revisions entailed extensive international discussions. The studies on which they were based revealed a lack of international uniformity in disease classification and thus basic problems regarding the reliability and comparability of vital statistical data.
Killing and the king: Numa's murder law and the nature of monarchic authority
Authors: GAUGHAN JUDY E.
Published: February 2004

The author makes the argument that the presence of a murder law during the Roman monarchy and the absence of such a law during the republic reflects the difference in the nature of authority in these two political institutions. The centralized authority of the monarchy demanded a control over the right to kill. An act of homicide practised by another infringed upon the king's authority and so a murder law was promulgated. When the Romans expelled their kings, authority devolved onto individual patres and this decentralized leadership under the republic meant that the act of homicide was no longer a matter of concern for the state.
Rights and wrongs in the confinement of the mentally incapable in eighteenth-century Scotland
Authors: HOUSTON R. A.
Published: February 2004

Improper confinement of those alleged to be mentally troubled was a prominent issue for the literate and propertied classes of eighteenth-century England and one which has fascinated historians too. In contrast, Scots did not perceive wrongful incarceration of the mentally disabled to be a serious social or legal issue. This article seeks to explain the differences between Scotland and England by focusing on a case where the care of a mentally troubled person was fought over. The article explores the familial settings and relationships involved in the care of the mad and idiotic and it shows medical and lay understandings of mental incapacity. Finally, it gives insights into the eclectic medical regime used to treat the mentally troubled and into the relationship between law, medicine and society. The argument is that different legal and medical structures meant that Scots were much less exercised about wrongful confinement. The article concludes that respect for the transparency of Scottish courts, for their cheapness and for their relative speed helped prevent the development of any extensive critique of improper confinement in eighteenth-century Scotland. Coupled with this was the relative power of the family compared with that of medical practitioners in Scotland.
Vessel Traffic Control Problems
Authors: Filipowicz Wlodzimierz
Published: February 2004

Separation schemes together with Vessel Traffic Services improve existing standards. Since their role has proved to be rather passive it is assumed that the introduction of active measures could be beneficial and improvement in terms of collision or accident risk reduction is expected. The concept raises a wide variety of problems that are to be discussed, defined and solved.
Consequences for Non-consequentialists
Authors: O'NEILL ONORA
Published: February 2004

Both consequentialist and non-consequentialist ethical reasoning have difficulties in accounting for the value of consequences. Taken neat, consequentialism is too fierce in its emphasis on success and disregard of luck, while non-consequentialism seemingly over-values inner states and undervalues actual results. In Uneasy Virtue Julia Driver proposes a form of objective consequentialism which claims that characters are good if they typically (but not invariably) produce good results. This position addresses the problems moral luck raises for consequentialism, but requires some form of realism about traits of character. However, if our knowledge of mental states is ascriptive, this form of objective consequentialism may make excessive demands. Non-consequentialists may gain in so far as the theories of action to which they are typically committed are less demanding, and are built to take account of the typical or systematic connections between states of character and results of action.