bluuebunny/crossref_metadata_2025 huggingface dataset:
The use of Web sites for SME innovation and technology support services in Wales
Authors: Thomas Brychan , Packham Gary , Miller Christopher , Brooksbank David
Published: September 2004

To stay at the forefront of new technology, small and medium‐sized enterprises (SMEs) can be assisted through Internet and Web sites providing innovation and technology support services. The cost of the latest technology, including hardware, training and personnel, however, can be insurmountable for SMEs with limited financial and technological resources. The business support community in Wales is continually evolving its own Internet and Web site offerings to make sure that businesses, especially SMEs, are kept abreast of the latest innovations, most productive methods and provision of support services. Considers the provision of Web‐based innovation and technology support in Wales and examines its coverage in relation to Welsh SMEs. Utilises a range of data collection techniques including interviews with policy makers and the analysis of reports and Internet sites.
Corporate taxonomies: report on a survey of current practice
Authors: Gilchrist Alan
Published: September 2004

Presents a report of a survey, based on case studies, of current practice in the building and use of taxonomies, with particular emphasis on corporate taxonomies to support enterprise information portals. Of the 22 case studies, six were designated as “core” and four are discussed in this paper: British Broadcasting Corporation, Glaxo Wellcome, Microsoft, and Unilever. Discusses key factors leading enterprises to consider the building of corporate taxonomies and describes the uses of taxonomies, principally as, inter alia, a source of authority for tagging, to aid navigation, to support search engines, as knowledge maps, and as a depository of enterprise retrieval languages. Key findings are presented.
Renardus: fostering collaboration between academic subject gateways in Europe
Authors: Huxley Lesly
Published: September 2004

Renardus is a collaborative project of the EU’s User‐friendly Information Society programme with partners from national libraries, university research and technology centres and subject gateways Europe‐wide. Its aim is to build a single service allowing users to search and browse existing Internet‐accessible scientific and cultural resource collections distributed across Europe. Renardus builds on the successes of subject gateway initiatives in Europe and elsewhere, and is evolving a collaborative model for addressing the increasingly difficult issues of sustainability and scalability facing individual gateway services. Describes the project’s context, progress to date and outstanding issues. Also outlines the opportunities and benefits for future collaboration with other organisations in developing the fully operational service.
Simplification strategies for simulation models of semiconductor facilities
Authors: Piplani Rajesh , Puah Sen Ann
Published: September 2004

Production planning using simulation has been gaining popularity as manufacturing routings become more complicated. However, a detailed simulation model that contains hundreds of machines and thousands of operations is far too large and complex to work with. The thesis in this research is that production planners at plant level do not need to see all the details of the shop floor to develop an effective production plan. Simulation model used for production planning can be simplified to ensure maintainability and manageability of the model. Model simplification is done in two stages, namely aggregation and condensation. Model aggregation reduces the number of routings in the model by using representative flows, whereas model condensation reduces the number of elements in a model by eliminating high throughput rate workstations. Both strategies reduce the complexity of a simulation model without sacrificing its accuracy. Experimental results using real‐life data indicate that the simplified model is a valid representation of the detailed model, and can be used for high level production planning.t‐Tests are used to compare the results of the detailed and simplified simulation model. Finally, rules of thumb are developed to standardize the simplification strategy.
Online point‐of‐click Web usability mining with PopEval (C‐Assure Co‐design methodology)
Authors: Badii Atta
Published: September 2004

Earlier research has shown that human judgements, particularly retrospective as distinct from real‐time evaluations of painful experiences, are fundamentally flawed when superseded by other experiences. Describes a methodology for the evaluation of user experiences, assisted by a user‐centered co‐design tool for planning, creating and conducting wide‐ranging usability data acquisition throughout the system life cycle from inception to replacement. The results from the tests in this study were found to support the findings from recent cognitive psychology research on J/DM‐PPR theoretic biasing effects. The importance of the findings for software systems, and for interactive Web site development, is that if the interactive features which tax the user's patience and cognitive capability are not severely restraining, then users will be left with a better impression of the usability of the system than would be the case otherwise.
Information technology evaluation: classifying indirect costs using the structured case method
Authors: Love Peter E.D. , Ghoneim Ahmad , Irani Zahir
Published: September 2004

Many companies are increasing their expenditure on information technology and information systems (IT/IS) to obtain or even sustain a competitive advantage in their respective marketplaces. Many managers, however, are often left with the quandary of how to evaluate their investments in technologies. Reasons of this difficulty have been suggested in the normative literature as centring on the socio‐technical (human, organisational and technical) dimensions associated with the adoption of IT/IS. The inability of managers to determine the true costs of deploying IT/IS is considered attributable to a lack of knowledge and understanding of IT/IS related costs. In developing a broader picture of such cost dimensions and their respective taxonomies, the research presented in this paper uses a structured case method to gain an understanding of how a construction firm embraced the IT evaluation process. A review of the IT cost literature is presented and a conceptual IT evaluation framework that focuses on indirect costs is proposed.
Quality Turnaround at IBM UK’s Information Network
Authors: Hobson Charles , Birchall Roger
Published: September 2004

States that for the first time a marketing unit has won the Market
Driven Quality (MDQ) Bronze Award from within IBM’s 50 business units.
The MDQ which is based on the Baldrige Award has been won by IBM UK’s
Information Network (IN), which is also the smallest unit in the
corporation to have achieved this award. States that IN provides a
variety of services for its customers on a worldwide basis. Explains
that its strong performance in increasing customer satisfaction is
mirrored in its business results. Shows how quality is implemented and
concludes that it is confident of maintaining these standards.
Fuzzy in control
Authors: Raber Rudi
Published: September 2004

Examines the problems of applying fuzzy logic to control applications
where each application is different from the previous one and looks at the
development of a unique system of fuzzy logic based on an existing software
package. The system comes in two alternative forms; the first is a fully
configurable fuzzy set for the OEM designer which, for example, could be used
to control the temperature of a large oven and the second reduces the fuzzy
function down to the most basic level where no process knowledge is required.
Describes the tests carried out in order to determine the linguistic
variables which apply to general control applications. Concludes that fuzzy
logic begins to take effect in those situation to which normal control
algorithms PD, PID functions have difficulty adjusting.
Advanced sensors seminar looks at multiplexing and NDT
Authors: Hollingum Jack
Published: September 2004

A report from a seminar on advanced sensing held on 9th November 1993 as
part of the DTI Advanced Sensors Technology Programme [ASTTP]. The first
subject covered was multiplexing for control systems and looked at the
present diversity of bus systems supporting field devices from the viewpoint
of sensor manufacturers, users and researchers. Another presentation relating
to multiplexing of sensors, looked at a project for water quality
measurement. The second topic was sensing in relation to
non‐destructive testing, dealing mainly with new market opportunities
in the food industry, the aircraft industry and civil engineering.
Probes for high precision dimensional measurement
Authors: Butler C
Published: September 2004

Looks at work carried out by The Centre for Manufacturing Metrology at
Brunel University into developing new probes for high precision dimensional
measurement. Describes the conventional “touch‐trigger” probe and the
errors in its performance. Also describes three prototype probes all based on
fibre optic principles: a two dimensional Triggering Probe; a three
dimensional Analogue Probe and a non‐contact probe. Concludes that the
2‐D triggering probe is a simple construction but limited to
2‐D operation; the analogue 3‐D is smaller in comparison with
existing types, comparable in accuracy and cheaper to manufacture, and the
non‐contact probe has potential for future development with some form
of “intelligent” data processing.
Scada uses radio to bridge the gap
Authors: Greeves Bill
Published: September 2004

Describes how radio telemetry can interface with process control systems
such as supervisory control and data acquisition [SCADA] and distributed
control systems [DCS] greatly increasing their power and efficiency. Outlines
the basis of radio telemetry, the behaviour of electromagnetic waves,
frequency and wavelengths. Uses the water industry as an example of the use
of a large scale and sophisticated SCADA system to provide date collection
and control links over a large area. Concludes that the versatility of radio
telemetry coupled with its cost‐effectiveness means that this
technology can help to expand and improve communications in an increasing
number of industries.
A new age gas meter
Authors: Grewal Simmy
Published: September 2004

Looks at the development of a new ultrasonic meter for the gas supply
industry and explaining the transit time measurement principle on which it
works and the performance characteristics of the new meter. Concludes that
the ultrasound gas meter could also have medical applications including
anaesthetics and hospital ward monitoring. There have been limited production
runs of the new gas meter and extensive trials are taking place in several
countries.
The impact of new technology in machine vision
Authors: Mackrory John , Daniels Mark
Published: September 2004

Outlines some of the areas in machine vision system solution which have
seen the most significant advances as a result of technology enhancement and
particularly the rapid development in semiconductor technology. Looks at the
background of machine vision development and improvements brought about by
modern technology, covering advances in vision algorithms, “warp engines”
used in combination with an application specific integrated circuit [ASIC],
improvements in human interface; and optical character recognition. Concludes
that the trend now is for general purpose vision processing systems to
provide greater capability, at greater throughput speed, without
significantly increasing the cost of the system which means that they are now
part of the original process design to inspect critical stages of
manufacture.
Surface finish scatters the light
Authors: Griffiths Brian J , Wilkie Bruce A , Middleton Russell H
Published: September 2004

Outlines research work into the assessment of light‐scattering
techniques for manufactured surfaces inspection. Describes the three type of
commercial sensors that have been available so far: glossometers, peak
intensity meters and light distribution measuring instruments and how they
work. Describes the laboratory rig supporting equipment and analysis
methodologies employed in order that numerous surfaces could be examined and
classified. The outcome was an atlas of typical manufactured surfaces and a
small ruggedized test bed sensor. Concludes that by using this rig and the
atlas the whole 3‐dimensional light scatter image can be examined to
select the appropriate sensor.
A syllabus for a World Wide Web writing workshop
Authors: Kayser Jack R.
Published: September 2004

Focusses on the successful format for Web writing used at Lafayette College. Presents an outline of the syllabus and provides advice on the knowledge, hardware and software necessary for running a Web‐writing workshop.
Worsening of Seizures by Oxcarbazepine in Juvenile Idiopathic Generalized Epilepsies
Authors: Gelisse Philippe , Genton Pierre , Kuate Callixte , Pesenti Aurélie , Baldy‐Moulinier Michel , Crespel Arielle
Published: September 2004

Summary:  Purpose: Several studies have shown that carbamazepine (CBZ) may aggravate idiopathic generalized epilepsy (IGE). Oxcarbazepine (OXC) is a new drug chemically related to CBZ. We report six cases of juvenile IGE with a clear aggravation by OXC.

Methods: We retrospectively studied all patients with IGE first referred to our epilepsy department between January 2001 and June 2003 and treated with OXC.

Results: During this period, six patients were identified. All had an aggravation of their epilepsy in both clinical and EEG activities. OXC had been used because of an incorrect diagnosis of focal epilepsy or generalized tonic–clonic seizures (GTCSs) of undetermined origin (no syndromic classification of the epilepsy). Before OXC, only one patient had experienced a worsening of seizures with an inadequate drug (CBZ). Four had juvenile myoclonic epilepsy, one had juvenile absence epilepsy, and one had IGE that could not be classified into a precise syndrome. OXC (dosage range, 300–1,200 mg/day) was used in monotherapy in all of them except for one patient. Aggravation consisted of a clear aggravation of myoclonic jerks (five cases) or de novo myoclonic jerks (one case). Three patients had exacerbation of absence seizures. One patient had worsened dramatically and had absence status, and one had de novo absences after OXC treatment. The effects of OXC on GTCSs were less dramatic, with no worsening in frequency in three and a slight increase in three.

Conclusions: OXC can be added to the list of antiepileptic drugs that can exacerbate myoclonic and absence seizures in IGE.
fMRI of Generalized Absence Status Epilepticus in Conscious Marmoset Monkeys Reveals Corticothalamic Activation
Authors: Tenney Jeffrey R. , Marshall Paul C. , King Jean A. , Ferris Craig F.
Published: September 2004

Summary:  Purpose: A nonhuman primate model of generalized absence status epilepticus was developed for use in functional magnetic resonance imaging (fMRI) experiments to elucidate the brain mechanisms underlying this disorder.

Methods: Adult male marmoset monkeys (Callithrix jacchus) were treated with γ‐butyrolactone (GBL) to induce prolonged absence seizures, and the resulting spike–wave discharges (SWDs) were analyzed to determine the similarity to the 3‐Hz SWDs that characterize the disorder. In addition, blood‐oxygenation‐level–dependent (BOLD) fMRI was measured at 4.7 Tesla after absence seizure induction with GBL.

Results: Electroencephalographic recordings during imaging showed 3‐Hz SWDs typical of human absence seizures. This synchronized EEG pattern started within 15 to 20 min of drug administration and persisted for >60 min. In addition, pretreatment with the antiepileptic drug, ethosuximide (ESM), blocked the behavioral and EEG changes caused by GBL. Changes in BOLD signal intensity in the thalamus and sensorimotor cortex correlated with the onset of 3‐Hz SWDs. The change in BOLD signal intensity was bilateral but heterogeneous, affecting some brain areas more than others. No significant negative BOLD changes were seen.

Conclusions: The BOLD fMRI data obtained in this marmoset monkey model of absence status epilepticus shows activation within the thalamus and cortex.
Dynamic Cortical Activity during Spasms in Three Patients with West Syndrome: A Multichannel Near‐infrared Spectroscopic Topography Study
Authors: Munakata Mitsutoshi , Haginoya Kazuhiro , Ishitobi Mamiko , Sakamoto Osamu , Sato Ikuko , Kitamura Taro , Hirose Mieko , Yokoyama Hiroyuki , Iinuma Kazuie
Published: September 2004

Summary:  Purpose: To investigate spatial and temporal cortical activity during clusters of naturally occurring epileptic spasms in patients with West syndrome (WS) by using multichannel near‐infrared spectroscopy (mNIRS).

Methods: Conventional magnetic resonance imaging (MRI) and interictal and ictal single‐photon emission computed tomography (SPECT) were carried out in three patients with WS. Thereafter, cortical hemodynamics during naturally occurring epileptic spasms were measured by mNIRS with simultaneous video/electroencephalographic (EEG) monitoring.

Results: Ictal SPECT revealed multiple hyperperfused areas within the cortex. With the use of mNIRS, an increase in regional cerebral blood volume (CBV) was observed in these areas, which is representative of cortical activation. The increase in CBV was accompanied by an increase in the concentrations of both oxy‐ and deoxyhemoglobin. The following heterogeneous regional changes in CBV during ictus were observed: (a) transient increases that were synchronized with spasms; (b) a gradual increase during an ictal event that fluctuated in synchrony with spasms; and (c) a combination of transient and gradual increases. An increase in regional CBV occurred in multiple areas that were activated either simultaneously or sequentially during an ictal event. Topographic changes in CBV were closely correlated with the phenotype of the spasm.

Conclusions: During ictal events, multiple cortical areas were activated simultaneously or sequentially. The pattern of cortical activation closely affected the phenotype of the spasm, which suggested that the cortex was involved in the generation of spasms.
Four hundred giant cities atop the world
Authors: Dogan Mattei
Published: September 2004

One of the most important social changes during the last decades has been the accelerated multiplication of giant cities and their growth in all continents, and mostly in the developing countries. The territorial nations are progressively becoming metropolitan states, in which mega‐cities and metropolises dominate the economic, social, cmfultural, and political life in many international spheres. The globalisation of the world mainly develops in and through the major cities, among which an intensive network of communication of goods, people, and ideas is developing. Social change is visible in many domains but the metropolitisation of the world is probably one of the most significant and well‐documented changes in the last decades.
Immigration and ethnic economies in giant cities
Authors: Light Ivan
Published: September 2004

Globalisation studies claimed that Third World immigrants flock to world cities because of changed income distributions. On this argument, the increasingly hourglass‐shaped income structure of world cities, a product of global restructuring, creates self‐renewing demand for skilled and unskilled workers in those very world cities. Critics have already shown that this argument neglects the intermediary role of migration networks, and that, when account is taken of these networks, a basis exists for explaining why migrations to world cities continue and even accelerate despite deteriorating economic conditions in the destinations. This paper addresses the role of ethnic economies in this perplexing process, arguing that ethnic economies buffer migrations from deteriorating economic conditions in the reception cities. This buffer expands effective demand for immigrant workers while guaranteeing pre‐migrants still at home employment and housing in the destinations prior to their actual departure. Assuming continuing immigration, a given of globalisation, the buffer itself is finally saturated after a lag. When combined with loss of local political toleration, which accompanies increasing poverty among migrants, the buffer's economic saturation finally diverts the migration network to lesser cities of the urban hierarchy where the process of mainstream saturation – buffer expansion – buffer saturation – dispersal repeats. The durability of buffer economies in localities does not depend only on economic conditions. Local political toleration of buffer economies importantly affects the durability of the immigration buffer in any city. To this extent, immigration policy is in the hands of cities, not of states.
Global cities in East Asia: empirical and conceptual analysis*
Authors: Smith David A.
Published: September 2004

East Asia is now the scene of very rapid and dynamic urban growth. Its great cities range from Tokyo (unquestionably a key “global city”) to Hong Kong, Seoul, and Taipei (ascending through the “world city” ranks) to Jakarta or Ho Chi Minh City (usually regarded as developing world “megacities”). How are social scientists to understand this dynamic of urbanisation and (under‐) development? This paper argues that we must begin with a framework that locates cities in global urban networks and in relation to world‐systemic changes. It sketches how the East Asian regional patterns “fit” with global ones. Finally, the essay suggests renewed focus on the “dependent / peripheral” cities at the “bottom” of the world urban hierarchy.
Two cultures of science: the limits of positivism*
Authors: Horowitz Irving Louis
Published: September 2004

In the nineteenth century, science was inseparably identified with progress. This optimism has given way to a pandemic mistrust of science by all sorts of elites. Yet this by no means reproduces the traditional opposition between science and the humanities. On the contrary, it reflects a clash within the culture of science itself. From a positivist perspective, knowledge goes with certainty. The destructive power of modern science, even in democratic societies, along with epistemological shifts within scientific practice itself, have favoured the emergence of a different and valuable conception of the relation between science and society, one that entails a certain tentativeness with respect to recommending policy and evaluating the need for new areas of investigation. In a democracy, the view of scientific knowledge as ethically indeterminate is both philosophically shaky and pragmatically indispensable.
On the status of logic in Piaget
Authors: Reginensi Luc
Published: September 2004

This article analyses the way in which Piaget links the analogy between the child and the primitive with a theory of the history of the sciences, that is, it analyses Piaget's version of Haeckel's principle in which ontogenesis recapitulates phylogenesis. From this analysis, we reconstitute the operations through which Piaget forms and expresses his conception of logic. In other words, we attempt to reconstruct the characteristic space of Piaget's non‐objectivated choices and positions that determines the conception of logic operative in his scientific and epistemological work.
Shortness of Breath and Abdominal Pain Within Minutes of Starting Hemodialysis
Authors: Rodby Roger A. , Bellucci Allessandro
Published: September 2004

A 45‐year‐old woman on hemodialysis without significant problems for 6 years developed acute onset of anxiety, shortness of breath, and abdominal pain within minutes of initiating her hemodialysis treatment. Her blood pressure was stable throughout the episode. The treatment was discontinued and she was admitted to the hospital. Routine blood chemistries were unremarkable except for mild eosinophilia (5%). An ethylene oxide reaction was suspected. She was dialyzed the following day after rinsing the dialyzer with 2 L of saline. A similar reaction occurred. The following day she was dialyzed on an ethylene oxide‐free dialyzer and the hemodialysis treatment was uneventful.
Hemodialysis‐Induced Hypotension: Impact of Technologic Advances
Authors: Donauer Johannes
Published: September 2004

Hemodialysis‐induced hypotension is one of the most serious complications in renal replacement therapy. The main cause of intradialytic hypotension is hypovolemia due to an imbalance between the amount of fluid removed and the refilling capacity of the intravascular compartment. Hypotension occurs when compensatory mechanisms for hypovolemia are overwhelmed by excessive fluid removal. As long as renal replacement therapy is limited to only a few hours per week, intradialytic hypotension will continue to be a relevant problem. Research has mainly focused on enlarging the compensatory capacity for ultrafiltration‐induced hypovolemia. This article critically discusses the technical approaches that have been introduced into therapy in recent years with the promise of reducing dialysis‐induced hypotensive episodes.
Inadequate Treatment of Cardiovascular Disease and Cardiovascular Disease Risk Factors in Dialysis Patients: A Commentary
Authors: Culleton Bruce F. , Hemmelgarn Brenda
Published: September 2004

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in patients with end‐stage renal disease (ESRD). Despite its significant impact on health outcomes, which would imply a need for aggressive intervention, both CVD and CVD risk factors are inadequately treated in this patient population. The reasons for this inadequate treatment are unclear. This article reviews the contribution of traditional risk factors to the burden of CVD in ESRD patients, outlines the evidence regarding undertreatment of CVD and traditional CVD risk factors, and identifies potential factors that may be responsible for inadequate cardiovascular care in ESRD patients.
Phylogeny ofMaculineablues (Lepidoptera: Lycaenidae) based on morphological and ecological characters: evolution of parasitic myrmecophily
Authors: Pech Pavel , Fric Zdeněk , Konvička Martin , Zrzavý Jan
Published: September 2004

A phylogeny of blue butterflies of the genusMaculineaand related genera (Lycaenidae) is proposed, based on 91 morphological and ecological characters. The resulting tree shows that: (1)Phengarisis a derived group nested withinMaculinea; (2) theMaculinea‐Phengarisclade is probably nested withinGlaucopsyche; (3) there are three well supported groups within theMaculinea‐Phengarisclade: (alcongroup ((teleiusgroup) (arion‐Phengarisgroup))). Some species (M. alcon,M. arionides) appear to be non‐monophyletic and require reclassification. The two alternative strategies of parasitic myrmecophily in theMaculinea‐Phengarisclade, viz., “predatory” and “cuckoo”, seem to be derived characters of thealcongroup, and of theteleiusandarion‐Phengarisgroups, respectively. The common ancestor ofMaculineaused dorsal nectary organ secretions for ant attraction, while this trait was reduced in the ancestor of thealcongroup and inM. nausithous(of theteleiusgroup). The three recentMaculinealineages utilize taxonomically diverse host plants, the asterid families Gentianaceae (alconandarion‐Phengarisgroups), Lamiaceae (arion‐Phengarisgroup), Campanulaceae (arion‐Phengarisgroup), and the rosid family Rosaceae (teleiusgroup).
Participation of Na/Ca‐exchanger and sarcoplasmic reticulum in the high [K]o‐protection against ischaemia‐reperfusion dysfunction in rat hearts
Authors: Consolini A. E. , Quiroga P. , Yuln G. , Volonté M. G.
Published: September 2004

Aim:  Na/Ca‐exchanger (NCX) and sarcoplasmic reticulum (SR) roles during the protection by a cardioplegic solution (25 mm K and 0.5 mm Ca, CPG) against ischaemia‐reperfusion was studied.

Methods:  Contractile performance (CP) and high energy phosphates contents (HEP) were evaluated in isolated ventricles from rats. They were pre‐treated with Krebs (C) or CPG and submitted to no‐flow ischaemia and reperfusion (I–R). KB‐R7943 5 μm (inhibitor of NCX in reverse mode), 8 mm caffeine and ionic changes were used pre‐ischaemically to evaluate each pathway role.

Results:  During R, CP recovered to 77 ± 8% of basal in CPG‐hearts vs. 55 ± 8% (P < 0.05) in C‐ones. CPG avoided the increases in end diastolic pressure (LVEDP) and in PCr/ATP ratio during I–R. Low [Na]o (78 mm) under both, CPG‐2 mm Ca and C, increased further the LVEDP during I–R. LVEDP was also transiently increased by caffeine‐CPG, but not modified by KB‐R7943. The recovery of CP during reperfusion of CPG‐hearts was decreased either, by caffeine (to ∼75%), low [Na]o‐2 mm Ca‐CPG (to ∼40%) and KB‐R7943 (to ∼16%).

Conclusions:  CPG protected hearts from ischaemic contracture by attenuating the fall in ATP and removing diastolic Ca by means of NCX in forward mode. Moreover, CPG induces higher CP recovery during reperfusion by participation of SR and NCX in reverse mode. This work remarks the use of CPG based on the functional role of these Ca handling‐mechanisms in a pathophysiological condition as ischaemia‐reperfusion.
Review article: oesophago‐gastric adenocarcinoma — an epidemiological perspective
Authors: Forman D.
Published: September 2004

This article reviews the epidemiology of cancers arising in the distal oesophagus and proximal stomach, sometimes collectively termed oesophago‐gastric junctional adenocarcinomas. The several complexities involved in defining this group of cancers are considered and the reported increasing trends in incidence are reviewed, together with the descriptive epidemiology. The rates of these cancers are increasing, but not as dramatically as sometimes reported. They are also more common in white males than in other ethnic groups or in females. Although several aetiological risk factors have been reported, the two most consistent are an elevated body mass index (obesity) and a history of gastro‐oesophageal reflux disease. Reflux is also associated with Barrett's oesophagus, an important and increasingly diagnosed premalignant lesion. The rate of progression from Barrett's oesophagus to cancer is controversial, as is the cost–benefit balance of routine endoscopic surveillance of such patients. The development of molecular biomarkers to identify Barrett's oesophagus patients with high rates of malignant transformation would represent a significant advance.
Review article: gastro‐oesophageal reflux disease — how wide is its span?
Authors: Talley N. J.
Published: September 2004

Symptoms of gastro‐oesophageal reflux disease are highly prevalent in Western countries; however, it is less certain how many individuals with heartburn have clinically relevant disease. Although the prevalence of gastro‐oesophageal reflux disease in Asia is substantially lower, the incidence may be increasing. How much of this increase is explained by the increasing recognition of heartburn in clinical practice, dietary changes and increasing obesity, or the eradication of Helicobacter pylori, remains unclear.

There has been speculation that endoscopy‐negative reflux disease represents a separate entity from reflux oesophagitis (as defined by the Los Angeles classification), but the evidence that might support this proposal is unconvincing.

Patients with chronic reflux symptoms have a higher risk of Barrett's oesophagus, and the increased risk of developing oesophageal adenocarcinoma in individuals with a long history of heartburn is also well documented, but whether this always occurs via Barrett's oesophagus is debatable. Moreover, treatment with standard‐dose antisecretory therapies and anti‐reflux surgery seems unlikely, based on current evidence, to reduce the cancer risk in patients with Barrett's oesophagus. Gastro‐oesophageal reflux disease has also been implicated in an increasing array of other conditions, but arguably in these settings it is often over‐diagnosed.
Review article: is stringent control of gastric pH useful and practical in GERD?
Authors: Kahrilas P. J.
Published: September 2004

As the relative efficacy of therapeutic agents in the treatment of gastro‐oesophageal reflux disease is related to how consistently and completely gastric acid secretion is suppressed, intragastric pH monitoring is a useful tool in stratifying therapies. If there is no acid in the stomach, there can be none to reflux into the oesophagus. Comparative crossover studies have shown consistently that once‐daily esomeprazole (40 mg) provides more effective and longer lasting intragastric acid control than any other proton pump inhibitor currently available in healthy subjects and patients with gastro‐oesophageal reflux disease. However, esomeprazole maintained intragastric pH > 4 for ≥ 16 h in only about 55% of individuals tested. Thus, if more complete acid suppression is desirable, twice‐daily proton pump inhibitor therapy may be advantageous.

One such scenario is in patients with Barrett's metaplasia. Data from the ProGERD study suggest that, for each Los Angeles grade of oesophagitis, the healing rate for patients with Barrett's metaplasia is 10–30% less than that for non‐Barrett's patients, being as low as 53% in patients with Los Angeles grade D oesophagitis. Also relevant to the Barrett's metaplasia population are studies on the oesophageal mucosa, which show that effective acid suppression favours differentiation and decreases epithelial cell proliferation. Both considerations argue for more intensive gastric acid inhibition than can be achieved with once‐daily therapy, leading to experimentation with twice‐daily proton pump inhibitor regimens.

A randomized, double‐blind, three‐way crossover study compared esomeprazole 40 mg once daily with esomeprazole 20 mg and 40 mg twice daily and found that both twice‐daily regimens were superior, maintaining intragastric pH > 4 for 73%[95% confidence interval (CI), 67–79%] and 80% (95% CI, 75–86%) of the day, respectively, compared with 59% (95% CI, 54–65%) of the day with esomeprazole 40 mg once daily, arguing that a twice‐daily regimen may be the preferred strategy for patients with Barrett's metaplasia.
Clinical strategies — interactive case discussions
Authors: Dent J. , Talley N. J.
Published: September 2004

Interactive case discussions held during the symposium illustrate the practical challenges and dilemmas faced in the management of Barrett's oesophagus. Opinions of the faculty and audience varied widely on how proton pump inhibitor therapy should be used, especially in patients with short‐segment Barrett's oesophagus. The therapeutic goal that received most support was to achieve sufficient acid control to keep the patient symptom free and heal any oesophagitis. At the same time, the patient should be reassured of the low risk associated with the endoscopic findings.

When long‐segment Barrett's oesophagus is detected, it should be assessed in detail, with targeted biopsy of any irregular‐surfaced metaplastic mucosa and four quadrant biopsies every 2 cm, to diagnose intestinal metaplasia and to screen for dysplasia or cancer. Repeat endoscopy and biopsy may be appropriate to achieve a sensitive initial assessment because of potential sampling error. Proton pump inhibitor therapy, often twice daily, was considered a requirement for most cases of long‐segment Barrett's oesophagus. There was disagreement over the role of surveillance, although proponents viewed it as worthwhile even in patients at low risk for the development of adenocarcinoma, mainly for medico‐legal reasons. Endoscopic mucosal resection was seen to be appropriate in carefully selected patients with high‐grade dysplasia, depending on factors such as age and comorbidity, the extent of high‐grade dysplasia, findings on endoscopic ultrasound and the length of Barrett's oesophagus.
Review article: management of oesophageal adenocarcinoma — control of acid, bile and inflammation in intervention strategies for Barrett's oesophagus
Authors: Jankowski J. A. , Anderson M.
Published: September 2004

Oesophagitis is associated with Barrett's metaplasia in about 10% of individuals. The UK has one of the highest world‐wide prevalences of Barrett's metaplasia, with 1% of adults having the condition, resulting in an incidence of oesophageal adenocarcinoma two to three times that seen in either Europe or North America. In addition, the conversion rate to cancer in individuals with Barrett's metaplasia in UK surveillance programmes is twice that observed in the USA (0.96% per year vs. 0.4% per year), lending further support to the notion that the UK is a high‐risk region. The evidence base on what can be achieved with medical therapy to reduce the risk of dysplasia or the development of adenocarcinoma needs to be strengthened with data from randomized controlled trials, as existing data have many limitations. Patients with Barrett's metaplasia respond variably to proton pump inhibitor therapy (even high‐dose therapy ‘normalizes’ acid reflux in only 85% of cases), and symptom control is a poor determinant of the adequacy of suppression of acid reflux. Gastro‐oesophageal reflux is implicated in the pathogenesis of Barrett's metaplasia, and ex vivo and in vitro evidence suggests that its attenuation reverses proliferation and biological variables over days, and perhaps the metaplastic histology to a degree over years. The effect of proton pump inhibitor therapy on cancer risk in the long term is essentially unknown. Acid suppressant therapy or anti‐reflux surgery on its own does not result in the complete regression of the metaplastic epithelium. Bile acids, present especially frequently in the refluxate of Barrett's oesophagus patients, are also likely to influence the development and persistence of metaplasia. Barrett's metaplasia is replaced by a squamous epithelium when acid reflux is well controlled and the epithelium is physically destroyed by ablation with argon plasma coagulation or photodynamic therapy. These modalities are invasive and are not likely to be useful in the routine management of patients with Barrett's oesophagus without dysplasia or cancer. Why metaplasia does not fully regress once external initiating stimuli are removed is a mystery. There is some evidence to implicate a variety of molecules, including cyclo‐oxygenase‐2, tumour necrosis factor‐α, β‐catenin nuclear translocation and mitogen‐activated protein kinase signalling, because they are expressed preferentially in metaplastic rather than normal or inflamed squamous oesophageal mucosa. The use of non‐steroidal anti‐inflammatory drugs, including aspirin, is associated with a decreased incidence of oesophageal adenocarcinoma. There is therefore a great need for randomized controlled trials to assess the outcomes of such chemopreventive therapy in patients with Barrett's metaplasia.
Regulation of GlnK activity: modification, membrane sequestration and proteolysis as regulatory principles in the network of nitrogen control in Corynebacterium glutamicum
Authors: Strösser Julia , Lüdke Alja , Schaffer Steffen , Krämer Reinhard , Burkovski Andreas
Published: September 2004

PII‐type signal transduction proteins play a central role in nitrogen regulation in many bacteria. In response to the intracellular nitrogen status, these proteins are rendered in their function and interaction with other proteins by modification/demodification events, e.g. by phosphorylation or uridylylation. In this study, we show that GlnK, the only PII‐type protein in Corynebacterium glutamicum, is adenylylated in response to nitrogen starvation and deadenylylated when the nitrogen supply improves again. Both processes depend on the GlnD protein. As shown by mutant analyses, the modifying activity of this enzyme is located in the N‐terminal part of the enzyme, while demodification depends on its C‐terminal domain. Besides its modification status, the GlnK protein changes its intracellular localization in response to changes of the cellular nitrogen supply. While it is present in the cytoplasm during nitrogen starvation, the GlnK protein is sequestered to the cytoplasmic membrane in response to an ammonium pulse following a nitrogen starvation period. About 2–5% of the GlnK pool is located at the cytoplasmic membrane after ammonium addition. GlnK binding to the cytoplasmic membrane depends on the ammonium transporter AmtB, which is encoded in the same transcriptional unit as GlnK and GlnD, the amtB‐glnK‐glnD operon. In contrast, the structurally related methylammonium/ammonium permease AmtA does not bind GlnK. The membrane‐bound GlnK protein is stable, most likely to inactivate AmtB‐dependent ammonium transport in order to prevent a detrimental futile cycle under post‐starvation ammonium‐rich conditions, while the majority of GlnK is degraded within 2–4 min. Proteolysis in the transition period from nitrogen starvation to nitrogen‐rich growth seems to be specific for GlnK; other proteins of the nitrogen metabolism, such as glutamine synthetase, or proteins unrelated to ammonium assimilation, such as enolase and ATP synthase subunit F1β, are stable under these conditions. Our analyses of different mutant strains have shown that at least three different proteases influence the degradation of GlnK, namely FtsH, the ClpCP and the ClpXP protease complex.
Identification of SpyA, a novel ADP‐ribosyltransferase of Streptococcus pyogenes
Authors: Coye Lisette H. , Collins Carleen M.
Published: September 2004

Streptococcus pyogenes, the aetiological agent of both respiratory and skin infections, produces numerous exotoxins to establish infection. This report identifies a new exotoxin produced by this organism, termed SpyA, for S. pyogenesADP‐ribosylating toxin. SpyA, MW 24.9, has amino acid identity with the ADP‐riboslytransferases (ADPRTs) Staphylococcus aureus EDIN and Clostridium botulinum C3. Recombinant SpyA was able to hydrolyse β‐NAD+, and this activity was dependent on a glutamate at position 187. SpyA has a putative biglutamate active site, and similar to most biglutamate ADPRTs, was able to ADP‐ribosylate poly‐l‐arginine. SpyA modified numerous proteins in both CHO and HeLa cell lysates. Two‐dimesional gel analysis and MALDI‐TOF MS analysis of modified proteins indicated that vimentin, tropomyosin and actin, all cytoskeletal proteins, are targets. Expression of spyA in HeLa cells resulted in loss of actin microfilaments. We hypothesize that SpyA is produced by S. pyogenes to disrupt cytoskeletal structures and promote colonization of the host.
YdgT, the Hha paralogue in Escherichia coli, forms heteromeric complexes with H‐NS and StpA
Authors: Paytubi Sònia , Madrid Cristina , Forns Núria , Nieto José María , Balsalobre Carlos , Uhlin Bernt Eric , Juárez Antonio
Published: September 2004

In enteric bacteria, proteins of the Hha/YmoA family play a role in the regulation of gene expression in response to environmental factors. Interaction of both Hha and YmoA with H‐NS has been reported, and an Hha/H‐NS complex has been shown to modulate expression in Escherichia coli of the haemolysin operon of plasmid pHly152. In addition to the hns gene, the chromosome of E. coli and other enteric bacteria also includes the stpA gene that encodes the StpA protein, an H‐NS paralogue. We report here the identification of the Hha paralogue in E. coli, the YdgT protein. As Hha paralogue, YdgT appears to fulfil some of the functions reported for StpA as H‐NS paralogue: YdgT is overexpressed in hha mutants and can compensate, at least partially, some of the hha‐induced phenotypes. We also demonstrate that YdgT interacts both with H‐NS and with StpA. Protein cross‐linking studies showed that YdgT/H‐NS heteromeric complexes are generated within the bacterial cell. The StpA protein, which is subjected to Lon‐mediated turnover, was less stable in the absence of Hha or YdgT. Our findings suggest that Hha, YdgT and StpA may form complexes in vivo.
PprA: a novel protein from Deinococcus radiodurans that stimulates DNA ligation
Authors: Narumi Issay , Satoh Katsuya , Cui Suzhen , Funayama Tomoo , Kitayama Shigeru , Watanabe Hiroshi
Published: September 2004

The extraordinary radiation resistance of Deinococcus radiodurans results from the efficient capacity of the bacterium to repair DNA double‐strand breaks. By analysing the DNA damage repair‐deficient mutant, KH311, a unique radiation‐inducible gene (designated pprA) responsible for loss of radiation resistance was identified. Investigations in vitro showed that the gene product of pprA (PprA) preferentially bound to double‐stranded DNA carrying strand breaks, inhibited Escherichia coli exonuclease III activity, and stimulated the DNA end‐joining reaction catalysed by ATP‐dependent and NAD‐dependent DNA ligases. These results suggest that D. radiodurans has a radiation‐induced non‐homologous end‐joining repair mechanism in which PprA plays a critical role.
Immunogenicity of Murein‐associated Proteins from Temperature‐stressed Streptococcus suis Cultures
Authors: Benga L. , Goethe R. , Große Beilage E. , Valentin‐Weigand P.
Published: September 2004

We compared immunogenicity in pigs of whole cell lysate proteins (WCP) with murein‐associated proteins (MAP) obtained from a virulent serotype 2 strain of Streptococcus (S.) suis grown at 32 or 42°C. Protein fractions were tested for their ability to induce antibodies in 3‐week‐old piglets by enzyme‐linked immunosorbent assay and Western blot analysis. We found a significant increase in the antibody levels in all sera irrespective of the preparation used for immunization. However, α‐WCP sera showed higher reactivities than α‐MAP sera, and piglets immunized with 32°C preparations (α‐32 sera) showed higher responses than those immunized with 42°C preparations (α‐42 sera). Western blot analysis revealed that α‐WCP sera in part reacted with different proteins when compared with α‐MAP sera. Furthermore, some proteins were only detected by α‐32 but not by α‐42 sera. In conclusion, the results demonstrate the immunogenicity of cell wall MAP of S. suis, and highlight the importance of considering growth conditions in the preparation of subunit vaccines.
Late Paleocene–middle Miocene pelagic sequences in the Boso Peninsula, Japan: New light on northwest Pacific tectonics
Authors: MOHIUDDIN MIA MOHAMMAD , OGAWA YUJIRO
Published: September 2004

Late Paleocene–middle Miocene pelagic limestone/chert sequences from the Mineoka Tectonic Belt, Boso Peninsula, central Japan, were biostratigraphically studied for planktic foraminifer fossils for the first time. The rock units are included as several isolated blocks tectonically within the ophiolitic mélange together with the Mio‐Pliocene Honshu arc‐derived terrigenous and Izu Arc‐derived volcaniclastic materials. The pelagic sequences are grouped into the newly proposed Kamogawa Group which is subdivided into the Paleocene Nishi Formation, Eocene–Oligocene Heguri‐Naka Limestone and early–middle Miocene Shirataki and Heguri Formations. This study of Kamogawa Group pelagic sequences throws new light on tectonic modeling of plate accretion to the unique trench–trench–trench (TTT)‐type triple junction area off the Boso Peninsula. Different formations of the Kamogawa Group have different tectonic and paleogeographic significances for the oceanic plate with a seamount that was approaching the Izu and Honshu arcs during Pacific plate subduction, and that was accreted to the Honshu Arc during the middle Miocene.