bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical islet transplant: current and future directions towards tolerance
Authors: Shapiro A. M. James , Nanji Sulaiman A. , Lakey Jonathan R. T.
Published: November 2003

Summary: The ultimate goal of islet transplantation is to completely correct the diabetic state from an unlimited donor source, without the need for chronic immunosuppressive drug therapy. Although islet transplantation provides an opportunity to develop innovative strategies for tolerance in the clinic, both alloimmune and autoimmune barriers must be controlled, if stable graft function is to be maintained long‐term. After islet extraction from the pancreas, the cellular graft may be stored in tissue culture or cryopreserved for banking, providing an opportunity not only to optimally condition the recipient but also to allowin vitroimmunologic manipulation of the graft before transplantation, unlike solid organ grafts. As such, islets may be considered a ‘special case.’ Remarkable progress has occurred in the last three years, with dramatic improvements in outcomes after clinical islet transplantation. The introduction of a steroid‐free, sirolimus‐based, anti‐rejection protocol and islets prepared from two (or rarely three) donors led to high rates of insulin independence. The ‘Edmonton Protocol’ has been successfully replicated by other centers in an international multicenter trial. A number of key refinements in pancreas transportation, processing, purification on non‐ficoll‐based media, storage of islets in culture for two days and newer immunological conditioning and induction therapies have led to continued advancement through extensive collaboration between key centers. This review outlines the historical development of islet transplantation over the past 30 years, provides an update on current clinical outcomes, and summarizes a series of unique opportunities for development and early testing of tolerance protocols in patients.
Effector mechanisms in transplant rejection
Authors: Rocha Paulo N. , Plumb Troy J. , Crowley Steven D. , Coffman Thomas M.
Published: November 2003

Summary:  Antigens, provided by the allograft, trigger the activation and proliferation of allospecific T cells. As a consequence of this response, effector elements are generated that mediate graft injury and are responsible for the clinical manifestations of allograft rejection. Donor‐specific CD8+ cytotoxic T lymphocytes play a major role in this process. Likewise, CD4+ T cells mediate delayed‐type hypersensitivity responses via the production of soluble mediators that function to further activate and guide immune cells to the site of injury. In addition, these mediators may directly alter graft function by modulating vascular tone and permeability or by promoting platelet aggregation. Allospecific CD4+ T cells also promote B‐cell maturation and differentiation into antibody‐secreting plasma cells via CD40–CD40 ligand interactions. Alloantibodies that are produced by these B cells exert most of their detrimental effects on the graft by activating the complement cascade. Alternatively, antibodies can bind Fc receptors on natural killer cells or macrophages and cause target cell lysis via antibody‐dependent cell‐mediated cytotoxicity. In this review, we discuss these major effector pathways, focusing on their role in the pathogenesis of allograft rejection.
Immunologic monitoring
Authors: Hernandez‐Fuentes Maria P. , Warrens Anthony N. , Lechler Robert I.
Published: November 2003

Summary:  The development of reliable in vitro assays that could allow the quantitation and characterization of anti‐donor alloimmune responses has always been a goal in clinical transplantation, both to predict presensitization to the transplanted tissue and to be able to identify rejection without resorting to more invasive tests. With recent development in our understanding of transplantation biology and therapeutics, there is a real expectation that these tests may be used to identify tolerance as much as to predict rejection. The traditional limiting dilution assays still have a contribution to make and are being complemented by an array of tools, such as ELISpot, flow cytometry‐based techniques, and microarray analysis. The assays that have been informative, to date, are discussed in this review. This information will lead, at least, to a better understanding of how and when the rejection process occurs. More interestingly, the objective is to apply this information to evaluate tolerance‐inducing strategies or to identify patients that have become tolerant to their graft and can be weaned of immunosuppression. Of course sensitive, accurate and specific immunologic monitoring has applications well beyond the field of transplantation.
Sun protection factor determination in vivo using a single exposure on sunscreen‐protected skin
Authors: Diffey Brian L.
Published: November 2003

Background: Determining sunscreen sun protection factors (SPFs) in a cohort of volunteers, particularly on products designed to provide high levels of protection, can be time‐consuming. The conventional approach is to administer to each subject a series of exposures (normally between five and seven) on their sunscreen‐protected skin.

Method: A method, based on Gaussian statistics, is proposed that requires just a single exposure on the sunscreen‐protected skin in volunteers to arrive at a reliable estimate of the mean SPF of a test product.

Results/Conclusion: The method is shown to yield an estimate of a product's mean SPF that is comparable, or better, in accuracy to estimates obtained by conventional multi‐exposure testing.
Artificial drainage of floodwaters from sulfidic backswamps: effects on deoxygenation in an Australian estuary
Authors: Johnston S. G. , Slavich P. G. , Sullivan L. A. , Hirst P.
Published: November 2003

The Clarence River estuary experienced extensive oxygen depletion and fish kills following overbank flooding in 2001. This paper examines the chemical composition and volume of surface water draining from two floodplain sulfidic backswamps into the Clarence River estuary after the flooding. Water draining from the backswamps was severely deoxygenated (<5 μmol L–1 O2), developed high chemical oxygen demand (~5000 μmol L–1) and became enriched in iron (~350 μmol L–1) during the weeks following the flood. The chemistry of this anoxic drainage water was influenced by anaerobic decomposition of backswamp vegetation, iron and sulfur biogeochemistry in backswamp surface sediments and shallow ground water input from acid sulfate soils. This study shows that artificial drainage of sulfidic backswamps increased the volume of anoxic surface water with high deoxygenation potential exported to the estuary, increasing the severity and duration of estuarine oxygen depletion in the latter stages (>6 days post-peak) of flood recession. In the absence of artificial drainage, most of the floodwaters with high deoxygenation potential would have been retained in the landscape and not exported to the estuary as observed during this flood.
Development and evaluation of a PCR-based test for detection of Asterias (Echinodermata : Asteroidea) larvae in Australian plankton samples from ballast water
Authors: Deagle B. E. , Bax N. , Hewitt C. L. , Patil J. G.
Published: November 2003

The northern Pacific seastar, Asterias amurensis, spread to Tasmania in the 1980s from its native range in the North Pacific. The seastar has subsequently established in Port Phillip Bay on mainland Australia. Transportation of larvae in ballast water is one vector for these introductions and is likely to contribute to additional range expansion of this species. Larval identification methods are critical to assess risks of further transport to uninvaded ecosystems; however, morphological identification of larval asteroids is impractical and unreliable. Therefore, we have developed a sensitive PCR-based method that specifically detects Asterias DNA. The method works on isolated seastar larva, mixed plankton and ballast water samples. Trials using uninfected ballast water samples spiked with known numbers of A. amurensis larvae indicate that the technique can detect single larva in 200 mg of plankton. The test also detects other Asterias species; therefore, discrimination between seastars within the genus Asterias was accomplished using denaturing gradient gel electrophoresis (DGGE). Currently, this method is being used to facilitate research on ballast water transport, distribution and the ecology of A. amurensis larvae. The general approach can be expanded to provide a rapid and cost-effective approach for detecting a suite of marine species in ballast water and environmental samples.
Grazing effects of the sea urchin Centrostephanus rodgersii in two contrasting rocky reef habitats: effects of urchin density and its implications for the fishery
Authors: Hill Nicole A. , Blount Craig , Poore Alistair G. B. , Worthington Duncan , Steinberg Peter D.
Published: November 2003

The sea urchin Centrostephanus rodgersii plays an important role in determining the abundance and composition of benthic macroalgae in New South Wales. Centrostephanus rodgersii is commonly found in areas devoid of foliose algae (termed 'barrens habitat'), which abruptly change into areas rich in foliose algae (termed 'fringe habitat'). Complementary experiments were used to investigate the impact of C. rodgersii grazing on algal assemblages at a range of densities in the barrens and fringe habitats. Although 33% of the natural density of C.�rodgersii maintained barrens areas relatively free of foliose algae, only densities exceeding natural densities within barrens habitat cleared areas dominated by macroalgae. The impact of grazing was not linearly related to density in either habitat, which suggests that both the barrens and fringe habitats are stable and will persist unless there is a dramatic decrease in urchin densities in barrens areas or a large influx into fringe areas. These findings have significant implications for the commercial harvesting of C. rodgersii. They imply that reducing urchin densities in barrens habitats, or translocating urchins from barrens to fringe habitats in order to improve roe quality, will not significantly alter the algal assemblage of either habitat in the short term (less than 3 months).
II. Veterans Affairs Cooperative Study of Polyenylphosphatidylcholine in Alcoholic Liver Disease
Authors: Lieber Charles S. , Weiss David G. , Groszmann Roberto , Paronetto Fiorenzo , Schenker Steven ,   for the Veterans Affairs Cooperative Study 391 Group
Published: November 2003

Background: Polyenylphosphatidylcholine (PPC) has been shown to prevent alcoholic cirrhosis in animals. Our aims were to determine the effectiveness of PPC in preventing or reversing liver fibrosis in heavy drinkers and to assess the extent of liver injury associated with the reduced drinking achieved in these patients.

Methods: This randomized, prospective, double‐blind, placebo‐controlled clinical trial was conducted in 20 Veterans Affairs Medical Centers with 789 patients (97% male; mean age, 48.8 years) averaging 16 drinks per day (1 drink = 14 g of alcohol) for 19 years. A baseline liver biopsy confirmed the presence of perivenular or septal fibrosis or incomplete cirrhosis. They were randomly assigned either PPC or placebo. Liver biopsy was repeated at 24 months, and the main outcome measure was the stage of fibrosis compared with baseline. Progression was defined as advancing to a more severe stage.

Results: The 2‐year biopsy was completed in 412 patients. PPC did not differ significantly from placebo in its effect on the main outcome. Alcohol intake was unexpectedly reduced in both groups to approximately 2.5 drinks per day. With this intake, 21.4% advanced at least one stage (22.8% of PPC patients and 20.0% of placebo patients). The hepatitis C virus–positive subgroup exhibited accelerated progression. Improvement in transaminases and bilirubin favoring PPC was seen at some time points in other subgroups (hepatitis C virus–positive drinkers or heavy drinkers).

Conclusions: PPC treatment for 2 years did not affect progression of liver fibrosis. A trend in favor of PPC was seen for transaminases and bilirubin (in subgroups). One of five patients progressed even at moderate levels of drinking, and thus health benefits commonly associated with moderate drinking do not necessarily extend to individuals in the early stages of alcoholic liver disease.
Consumer acceptance of functional foods: issues for the future
Authors: Frewer Lynn , Scholderer Joachim , Lambert Nigel
Published: November 2003

In the past, it has been assumed that consumers would accept novel foods if there is a concrete and tangible consumer benefit associated with them, which implies that functional foods would quickly be accepted. However, there is evidence that individuals are likely to differ in the extent to which they are likely to buy products with particular functional properties. Various cross‐cultural and demographic differences in acceptance found in the literature are reviewed, as well as barriers to dietary change. In conclusion, it is argued that understanding consumers’ risk perceptions and concerns associated with processing technologies, emerging scientific innovations and their own health status may enable the development of information strategies that are relevant to wider groups of individuals in the population, and deliver real health benefits to people at risk of, or suffering from, major degenerative illnesses.
Self‐efficacy: a concept closely linked to information literacy and lifelong learning
Authors: Serap Kurbanoglu S.
Published: November 2003

This paper is primarily concerned with self‐efficacy in the context of information literacy. The focus is first on the concept of self‐efficacy, followed by attainment of self‐efficacy beliefs. Finally, findings of the research, the aim of which was to explore students’ (who enrolled in the Department of Information Management, Hacettepe University, Ankara, Turkey) perceived self‐efficacy for information and computer literacy, are scrutinized. Results of the research indicate no significant year‐to‐year changes, although the students have a positive perceived self‐efficacy for information literacy. Students’ self‐efficacy beliefs regarding information literacy and computers are correlated.
A study of operations management constructs and their relationships
Authors: Choon Tan Keah , Wisner Joel D.
Published: November 2003

This paper describes an exploratory research effort to analyze and classify emerging operations management practices in US manufacturing. Using a survey of senior materials and operations management professionals in the United States, this study investigates manufacturers' supplier assessment practices, new product design and development practices, just‐in‐time practices, and quality practices. This study also identifies practices that share common variance‐covariance characteristics and to what extent the observed practices are linked to their underlying factors by means of exploratory factor analysis. Finally, bivariate correlation analysis is used to examine the relationships of the factors.
Lean manufacturing in temperature dependent processes with interruptions
Authors: Lee W.L. , Allwood J.M.
Published: November 2003

A particular difficulty arises when lean manufacturing principles are applied to temperature dependent processes. Specifically, when an interruption occurs, lean manufacturing advocates stopping the production line to find the “root cause” of the problem. However, interruptions in temperature dependent processes will cause work‐in‐progress and process equipment to cool down and quality problems are likely when production restarts. This difficulty could be countered through a detailed process model, but apart from the difficulty of creating perfect process models with accurate inputs, the use of such a system would separate shop floor operators from the problem‐solving process. Instead, a response to interruptions is sought in the form of a “script” of actions which can be used to train operators. In order to develop an appropriate script, a generic model of a set of temperature dependent processes is defined in which the states of processes and products are time dependent. A hypothetical profit function is defined for the processes and it is shown how this could be optimized by dynamic programming. The dynamic programming process is then translated into a script to guide operators in decision‐making during interruptions. The script is demonstrated with a simulation model of an extrusion process, and the results suggest that the new script will result in improved throughput and reduced scrap in the presence of interruptions.
Service operations strategy, flexibility and performance in engineering consulting firms
Authors: Arias Aranda Daniel
Published: November 2003

In this paper, the relationship between operations strategy and performance through flexibility as a moderating variable is analysed within the service setting of engineering consulting firms in Spain. A framework for service strategy dimensions is suggested while manufacturing flexibility dimensions are applied to service operations considering necessary adaptations. A path analysis model is applied in order to enhance the understanding of interactions. This research proves that service operations strategy has a significant positive and direct effect on service delivery performance. The fact that is especially relevant is that flexibility plays a more intense moderating role for efficiency performance measures than for customer satisfaction performance measures.
Dependency and its predictions for systems and its components
Authors: Vaidya Omkarprasad S. , Kumar Sushil
Published: November 2003

This study builds up the case for dependency considerations in system analyses by explaining “dependency” as a concept, and proposes a methodology to predict the dependency for the components and the systems. Many a times, dependency concept is neglected in system studies in order to simplify the analysis that leads to the “satisficing” results. For systems where such negligence may cause significant deviations, the dependency has to be accounted for. The proposed methodology applies the concepts of analytic hierarchy process (AHP), directed graph, and matrices at different stages of analyses and results into an intra‐dependency index for the system. This index could help the analyst select the less dependent system from amongst the choices available without compromising on the minimum expectations of the system. The index would also help understand the level of the dependencies in the system. In this paper, the methodology is developed and described using examples, to explain the application of functional dependency and design dependency. This suggests the wide coverage and application of the proposed methodology.
Hypermarket retail store efficiency in Portugal
Authors: Pestana Barros Carlos , Alves Carlos Alberto
Published: November 2003

This paper analyses the efficiency of individual retail stores belonging to a Portuguese multi‐market hypermarket retailing chain, employing data envelopment analysis (DEA). The use of DEA for the analysis of intra‐chain comparative store efficiency can be of value in examining the competitiveness of the chain as a whole. Competitiveness should be based on benchmarking the retail outlets which compose the chain. We conclude from our research that some outlets are at the frontier of best practice, while others are inefficient. Managerial implications arising from the study are considered.
Internet anonymity practices in computer crime
Authors: Armstrong H.L. , Forde P.J.
Published: November 2003

Money laundering, drug dealing, terrorism, hacking, fraud, child pornography and the distribution of objectionable material are crimes that are perpetrated using the Internet. Criminals utilise software tools and valuable knowledge from the Internet as well as embracing the Internet’s global communications system to participate in virtual communities of disguised people. The Internet provides the facilities for people with criminal intent to associate and exchange intelligence with reduced risk to their personal identification. Using the example of paedophile and hacker Internet practice, this paper proposes an association between criminal Internet activity and Internet anonymity. It discusses the propensity to use anonymity techniques when perpetrating cyber crime. Consequently, a new balance between privacy, freedom of speech and law enforcement must be determined.
Intrusion detection: methods and systems. Part II
Authors: Sherif Joseph S. , Ayers Rod
Published: November 2003

This paper is part II of a previous article of the same title: Intrusion detection. Part II is concerned with intrusion threats, attacks, defense, models, methods and systems.
A security risk management approach for e‐commerce
Authors: Warren M. , Hutchinson W.
Published: November 2003

E‐commerce security is a complex issue; it is concerned with a number of security risks that can appear at either a technical level or organisational level. This paper uses a systemic framework, the viable system model (VSM) to determine the high level security risks and then uses baseline security methods to determine the lower level security risks.
Informing IT system Web site design through normalisation
Authors: Taylor M.J. , Wade S. , England D.
Published: November 2003

Designing a truly customer focused Web site can be difficult. This paper examines the approach of adapting the existing database design technique of normalisation for achieving customer focused Web site design. A Web site can be thought of as a multimedia database, in fact under European law a Web site is legally classified as being a database. In traditional database design, normalisation is used to structure data and provide efficient keys for data retrieval. In Web site normalisation “data” is now the text, images, and functions (for example, e‐mail and ordering goods) that are required on the Web site. Keys for “data” are now Web site headings, sub‐groupings, and topics. Web site normalisation allows the Web site designer to structure Web site material and identify the optimal Web site navigational structure from a customer perspective, and thus, produce a truly customer focused Web site. A case study in a UK marketing organisation is provided in order to demonstrate and evaluate Web site normalisation in action.
Web advertising: gender differences in beliefs, attitudes and behavior
Authors: Wolin Lori D. , Korgaonkar Pradeep
Published: November 2003

Previous research suggests males and females exhibit different beliefs about and attitudes toward traditional media advertising along with different advertising stimulated consumer behaviors. However, little is known about gender differences in consumer beliefs about Web advertising versus other media, attitude toward Web advertising, or Web advertising associated consumer behavior. Survey results indicate males and females differ significantly on several dimensions with males exhibiting more positive beliefs about Web advertising and more positive attitudes toward Web advertising than females. Additionally, males are more likely than females to purchase from the Web and surf the Web for functional and entertainment reasons, whereas females are more likely to surf the Web for shopping reasons.
Conflicts among Net news participants and cultural background
Authors: Yano Masaharu , Seo Yuzo
Published: November 2003

Participants in Internet net news bulletin board discussions can argue with others whom they do not know. The nature of each message in a discussion can be characterized by the frequency with which keywords appear in the message. This incidence or frequency can be summarized as a principal component score. By deriving two characteristic indexes – auto‐correlation coefficients and power spectra – from the principal component scores, we have come up with a novel method. Applying this method to analyze three large net news threads, the index plots revealed two‐generation cyclic fluctuations. Comparing these plots with actual points of conflict obtained by reading the message contents, a fairly good correlation was obtained between the two and it was found that most of the conflicts were among participants with different cultural backgrounds.
Blending “we/me” in performance management
Authors: Brumback Gary B.
Published: November 2003

In a team‐based organization, the performance not only of the teams as a whole but also of their individual members needs to be managed and managed very well if tall performance (consistently competent, ethical, and motivated behavior that always produces the best results) is to be reached and sustained. In this article, four principles are first overviewed that underlie a new model of performance management designed by the author. The principles are those of tall performance, accountability, responsible empowerment, and performance management. An overview of the new model is then given. Among the model’s salient features are the way it preserves the “we” without sacrificing the “me”, a non‐traditional way to do performance appraisals, and accountability not only for results but also for behaviors, including ethical conduct.
Competition in the local loop: unbundling or unbungling?
Authors: Ure John
Published: November 2003

Unbundling has been the widely adopted regulatory solution to introducing competition in the local loop. But what is the aim of unbundling? Is it an end in itself, or a means to an end? Experience from around the world suggests there is as yet no clear cut evidence one way or the other that unbundling encourages facilities competition, or that it encourages investment in broadband networks in particular. This article considers the case for unbundling the local loop in Hong Kong and examines the experience in countries such as the EU, the UK, USA, Canada, South Korea and Japan.
The Role of Free Radicals in the Muscle Vasodilatation of Systemic Hypoxia in the Rat
Authors: Pyner Susan , Coney Andrew , Marshall Janice M.
Published: November 2003

Muscle vasodilatation evoked by systemic hypoxia is adenosine mediated and nitric oxide (NO) dependent: recent evidence suggests the increased binding of NO at complex IV of endothelial mitochondria when O2 level falls leads to adenosine release. In this study on anaesthetised rats, the increase in femoral vascular conductance (FVC) evoked by systemic hypoxia (breathing 8% O2 for 5 min) was reduced by oxypurinol which inhibits xanthine oxidase (XO): XO generates O2− from hypoxanthine, a metabolite of adenosine. By contrast, infusion of superoxide dismutase (SOD), which dismutes O2− to hydrogen peroxide (H2O2), potentiated the hypoxia‐evoked increase in FVC. However, NO synthesis inhibition reduced the hypoxia‐evoked increase in FVC and it was not further altered by SOD. In other studies, the spinotrapezius muscle was pre‐loaded with hydroethidine (HE), or dihydrorhodamine (DHR) which fluoresce in the presence of O2− and H2O2, respectively. In muscle loaded with HE, systemic hypoxia increased fluorescence in endothelial cells of arterioles, whereas in muscle loaded with DHR, fluorescence was diffusely located in and around arteriolar endothelium. We propose that in systemic hypoxia, O2− generated by the XO degradation pathway from adenosine released by endothelial cells, and released by endothelial mitochondria by increased binding of NO to complex IV, is dismuted to H2O2, which facilitates hypoxia‐induced dilatation.
Characterization of Zebrafish Cx43.4 Connexin and its Channels
Authors: Desplantez T. , Marics I. , Jarry‐Guichard T. , Veteikis R. , Briand J.‐P. , Weingart R. , Gros D.
Published: November 2003

Connexins (Cx) form intercellular junctional channels which are responsible for metabolic and electrical coupling. We report here on the biochemical and immunohistochemical characterization of zebrafish connexin zfCx43.4, an orthologue of mammalian and avian Cx45, and the electrophysiological properties of junctional channels formed by this protein. The investigations were performed on transfected COS‐7 cells or HeLa cells. Using site‐directed antibodies, zfCx43.4 cDNA (GenBank accession no. X96712) was demonstrated to code for a protein with a Mr of 45 000. In transfected cells, zfCx43.4 was localized in cell‐cell contact areas as expected for a gap junction protein. zfCx43.4 channels were shown to transfer Lucifer Yellow. The multichannel currents were sensitive to the transjunctional voltage (Vj). Their properties were consistent with a two‐state model and yielded the following Boltzmann parameters for negative/positive Vj: Vj,0= ‐38.4/41.9 mV; gj,min= 0.19/0.18; z = 2.6/2.3. These parameters deviate somewhat from those of zfCx43.4 channels expressed in Xenopus oocytes and from those of Cx45, an orthologue of zfCx43.4, expressed in mammalian cells or Xenopus oocytes. Conceivably, the subtle differences may reflect differences in experimental methods and/or in the expression system. The single channel currents yielded two prominent levels attributable to a main conductance state (γj,main= 33.2 ± 1.5 pS) and a residual conductance state (γj,residual= 11.9 ± 0.6 pS).
Discharge Patterns of Preganglionic Neurones with Axons in a Cardiac Vagal Branch in the Rat
Authors: O'Leary Deirdre M. , Jones James F. X.
Published: November 2003

The fibre types that run in a vagal branch projecting to the rat heart are described in this study. In order to obtain spontaneous discharge in this vagal branch and optimal recording conditions, we compared the decerebrate state to urethane, urethane‐chloralose and pentobarbital‐chloralose anaesthesia with regard to level of chronotropic cardiac vagal tone. Administration of atropine (2 mg kg−1, I.V.) significantly decreased baseline cardiac interval only in the decerebrate and urethane‐anaesthetised rat (by 0.018 ± 0.001 s and 0.019 ± 0.002 s, respectively). As a result of these experiments, urethane was chosen as the anaesthetic for all subsequent studies. Using a heart rate signal‐averaging method we demonstrated that rat cardiac vagal preganglionic neurones innervating the sinoatrial node should have an expiratory discharge pattern, as reported in other species. However, only 5% of chronotropic vagal tone was found to be subject to respiratory sinus arrhythmia. A suction microelectrode method, combined with spike‐triggered averaging, was employed to record activity from a total of 58 vagal afferents that had axons in this branch. Approximately 75% of these latter sensory fibres displayed cardiac rhythm. In a separate study we also recorded 318 preganglionic neurones with axons in the right cardiac vagal branch of the rat. Respiratory‐modulated preganglionic units were statistically less common than tonically firing units. Six preganglionic subtypes were categorised according to conduction velocity and respiratory discharge pattern. Myelinated B‐fibre and unmyelinated C‐fibre types were found to be equally prevalent and equally likely to be reflexly excited during the pulmonary chemoreflex and the peripheral arterial chemoreflexes. The electrophysiological analysis has shown how diverse the discharge patterns of the preganglionic neurones or interneurones are whose axons course in the right cardiac vagal branch of the rat. The results of these experiments demonstrate the usefulness of combining spike discrimination with multiple spike‐triggered averaging to simultaneously record B and C centrifugal vagal efferents.
Influence of Pregnancy on Plasma Cytokines and the Febrile Response to Intraperitoneal Administration of Bacterial Endotoxin in Rats
Authors: Fofie Anita E. , Fewell James E.
Published: November 2003

Rats have an attenuated febrile response to exogenous (e.g. bacterial endotoxin) and endogenous pyrogen (e.g. interleukin‐1β) near the term of pregnancy, the mechanism of which is unknown. The present experiments were carried out on 71 non‐pregnant and 181 pregnant Sprague‐Dawley rats to determine if basal levels of the endogenous antipyretic substance, interleukin‐1 receptor antagonist (IL‐1ra), change relative to interleukin‐1β (IL‐1β) throughout gestation. Furthermore, we have constructed complete Escherichia coli lipopolysaccharide (LPS) dose‐core temperature response curves in non‐pregnant and pregnant rats on days 10, 15 and 20 of gestation (term of gestation ∼21 days) to determine if the attenuated febrile response near the term of pregnancy results from a simple shift of the dose‐response relationship or results from a dampening of the overall dose‐response relationship. Basal IL‐1β, as determined by ELISA on trunk blood from non‐pregnant and pregnant rats on days 10, 15 and 20 of gestation (d10, d15, d20), did not change significantly during pregnancy. Basal IL‐1ra, however, was increased significantly in d15 rats as compared to non‐pregnant, and d10 and d20 rats. The attenuated febrile response near the term of pregnancy, as determined by biotelemetry, did not result from a simple shift of the E. coli LPS dose‐core temperature response curve but rather a dampening of the overall dose‐response relationship. The febrile responses to EC50 and EC100 doses of E. coli LPS were preceded by a period of hypothermia, and were delayed and attenuated near the term of pregnancy as compared to that observed early in pregnancy and in non‐pregnant rats. Our data provide evidence that pregnant rats are more sensitive to the hypothermia‐producing effects of E. coli LPS than are non‐pregnant rats and allow us to speculate that elevated basal IL‐1ra may play a role in mediating the attenuated febrile response to pyrogen on day 15 but not on day 20 of gestation in rats.
Cardioventilatory Coupling in Resting Human Subjects
Authors: Tzeng Y. C. , Larsen P. D. , Galletly D. C.
Published: November 2003

In 48 conscious resting subjects we examined the temporal coupling of heart beat timing and the onset of inspiration (cardioventilatory coupling), and the relationship between coupling and spectral indices of autonomic function. Using the proportional Shannon entropy (SHα) of the RI‐1 interval (interval between inspiration and the preceding ECG R wave) as a measure of coupling we detected statistically significant coupling in 32 of the 48 subjects. This was confirmed by visual inspection of time series plots of RI intervals, in which coupling was evident as horizontal banding. Coupling resulted in a significant preference for whole number heart rate/respiratory frequency ratios. The strongest coupling was associated with low ventilatory frequency and high heart rate variability in the high (0.15‐0.40 Hz) and low (0.04‐0.15 Hz) frequency ranges, but was not related to blood pressure variability, or to a spectral measure of baroreflex sensitivity (α‐index, low frequency range). There was no difference in coupling strength between males and females. We have previously described cardioventilatory coupling in spontaneously breathing anaesthetised subjects. The current study extends those observations by demonstrating that the qualitative features of coupling seen during anaesthesia are also observed in the conscious state. We conclude that the role of coupling in normal physiological respiratory control needs to be more widely explored.
Hypothyroidism Attenuates Stress‐Induced Prolactin and Corticosterone Release in Septic Rats
Authors: Rodriguez T. T. , Albuquerque‐Araújo W. I. C. , Reis L. C. , Antunes‐Rodrigues J. , Ramalho M. J.
Published: November 2003

We investigated the effects of sepsis, through the lipopolysaccharide (LPS)‐induced inflammatory response, on plasma corticosterone and prolactin (PRL) levels during acute immobilization stress in normal and thyroidectomized rats. Thyroidectomized (TX) or sham‐operated (N) rats were subjected to 120 min of immobilization stress. Rats were treated with an intraperitoneal injection of either LPS (250 μg (100 g body wt)−1) or the same volume of vehicle (saline solution), 90 min before the induction of stress. Blood samples for hormone assays were collected before sepsis and stress induction for baseline measures (‐90 min), and during sepsis and immobilization stress for the measurement of prolactin and corticosterone levels by radioimmunoassay. Our results show that the thyroid hormones are necessary for a proper response of PRL and corticosterone release during immobilization stress. Although sepsis enhanced PRL secretion, this was not true of corticosterone release in either group of rats. Low levels of thyroid hormones partially block the release of PRL, but do not block corticosterone secretion during sepsis.
Differential Effect of head‐up tilt on Cardiovagal and Sympathetic Baroreflex Sensitivity in Humans
Authors: O'Leary D. D. , Kimmerly D. S. , Cechetto A. D. , Shoemaker J. K.
Published: November 2003

The purpose of this study was to determine the effect of baroreceptor unloading on the sensitivity of the cardiovagal and sympathetic arms of the baroreflex during upright posture. Beat‐by‐beat R‐R interval, arterial blood pressure and cardiac output (Doppler ultrasound), as well as muscle sympathetic nerve activity (MSNA) were recorded during periods in supine (Supine) and 60 deg head‐up tilt (HUT) positions (n = 8 volunteers). Cardiovagal baroreflex sensitivity (BRS) was measured by the spontaneous sequence analysis method using systolic blood pressure and R‐R interval, while sympathetic BRS was determined using the slope of the linear relationship between decreasing segments of diastolic blood pressure (DBP) and corresponding increases in MSNA. On changing to HUT, mean R‐R interval and cardiac output decreased, while mean measures of MSNA, DBP and total peripheral resistance increased (P < 0.05). Cardiovagal BRS decreased from Supine to 60 deg HUT (19 ± 2 ms mmHg−1 versus 7.6 ± 1.2 ms mmHg−1; P < 0.01). In contrast, sympathetic BRS increased from ‐6.1 ± 1.4 a.u. mmHg−1 in Supine to ‐14 ± 2 a.u. mmHg−1 in HUT (P < 0.01). Thus, HUT produced differential effects on cardiac versus sympathetic BRS. The data suggest that dynamic baroreflex‐mediated cardiovascular control is dominated by sympathetic control during baroreceptor unloading.
Nitric Oxide Synthesis Requires Activity of the Cationic and Neutral Amino Acid Transport System y+L in Human Umbilical vein Endothelium
Authors: Arancibia‐Garavilla Yerko , Toledo Fernando , Casanello Paola , Sobrevia Luis
Published: November 2003

L‐Arginine transport is mediated by the cationic/neutral amino acid transport system y+L and cationic amino acid transporters y+/CATs in human umbilical vein endothelial cells (HUVECs). System y+/CATs activity may be rate‐limiting for nitric oxide (NO) synthesis, but no reports have demonstrated system y+L involvement in NO synthesis in endothelium. We investigated the role of system y+L in NO synthesis in HUVECs. Transport of 1.5 μM L‐arginine was inhibited (P < 0.05) by L‐lysine (Ki, 1.4 μM), L‐leucine (Ki, 1.8 μM) and L‐phenylalanine (Ki, 4.1 μM), but was unaltered (P > 0.05) by L‐alanine or L‐cysteine. The system y+/CATs inhibitor, N‐ethylmaleimide (NEM), did not alter 1.5 μM L‐arginine transport, but inhibited (92 ± 3%) 100 μM L‐arginine transport. L‐Arginine transport in the presence of NEM was saturable (Vmax, 0.37 ± 0.02 pmol (μg protein)−1 min−1; Km, 1.5 ± 0.3 μM) and competitively inhibited by L‐leucine in the presence of Na+ (Vmax, 0.49 ± 0.06 pmol (μg protein)−1 min−1; Km, 6.5 ± 0.9 μM). HUVECs express SLC3A2/4F2hc, SLC7A7/4F2‐lc2 and SLC7A6/4F2‐lc3 genes encoding for the high‐affinity transport system y+L. NG‐Nitro‐L‐arginine methyl ester and L‐leucine, but not NEM, inhibited NO synthesis in medium containing 1.5 μM L‐arginine. Cells exposed to 25 mM D‐glucose (24 h) exhibited reduced system y+L activity (Vmax, 0.15 ± 0.008 pmol (μg protein)−1 min−1; Km, 1.4 ± 0.3 μM) and NO synthesis. However, 25 mM D‐glucose increased NO synthesis and L‐arginine transport via system y+. Thus, L‐arginine transport through system y+L plays a role in NO synthesis, which could be a determining factor in pathological conditions where the endothelial L‐arginine‐NO pathway is altered, such as in diabetes mellitus.
Control of Nutrient-Sensitive Transcription Programs by the Unconventional Prefoldin URI
Authors: Gstaiger Matthias , Luke Brian , Hess Daniel , Oakeley Edward J. , Wirbelauer Christiane , Blondel Marc , Vigneron Marc , Peter Matthias , Krek Wilhelm
Published: November 2003

Prefoldins (PFDs) are members of a recently identified, small–molecular weight protein family able to assemble into molecular chaperone complexes. Here we describe an unusually large member of this family, termed URI, that forms complexes with other small–molecular weight PFDs and with RPB5, a shared subunit of all three RNA polymerases. Functional analysis of the yeast and human orthologs of URI revealed that both are targets of nutrient signaling and participate in gene expression controlled by the TOR kinase. Thus, URI is a component of a signaling pathway that coordinates nutrient availability with gene expression.
Islet Regeneration During the Reversal of Autoimmune Diabetes in NOD Mice
Authors: Kodama Shohta , Kühtreiber Willem , Fujimura Satoshi , Dale Elizabeth A. , Faustman Denise L.
Published: November 2003

Nonobese diabetic (NOD) mice are a model for type 1 diabetes in humans. Treatment of NOD mice with end-stage disease by injection of donor splenocytes and complete Freund's adjuvant eliminates autoimmunity and permanently restores normoglycemia. The return of endogenous insulin secretion is accompanied by the reappearance of pancreatic β cells. We now show that live donor male or labeled splenocytes administered to diabetic NOD females contain cells that rapidly differentiate into islet and ductal epithelial cells within the pancreas. Treatment with irradiated splenocytes is also followed by islet regeneration, but at a slower rate. The islets generated in both instances are persistent, functional, and apparent in all NOD hosts with permanent disease reversal.
CLIP Identifies Nova-Regulated RNA Networks in the Brain
Authors: Ule Jernej , Jensen Kirk B. , Ruggiu Matteo , Mele Aldo , Ule Aljaž , Darnell Robert B.
Published: November 2003

Nova proteins are neuron-specific antigens targeted in paraneoplastic opsoclonus myoclonus ataxia (POMA), an autoimmune neurologic disease characterized by abnormal motor inhibition.Nova proteins regulate neuronal pre-messenger RNA splicing by directly binding to RNA.To identify Nova RNA targets, we developed a method to purify protein-RNA complexes from mouse brain with the use of ultraviolet cross-linking and immunoprecipitation (CLIP).Thirty-four transcripts were identified multiple times by Nova CLIP.Three-quarters of these encode proteins that function at the neuronal synapse, and one-third are involved in neuronal inhibition.Splicing targets confirmed in Nova
–/–
mice include c-Jun N-terminal kinase 2, neogenin, and gephyrin; the latter encodes a protein that clusters inhibitory γ-aminobutyric acid and glycine receptors, two previously identified Nova splicing targets.Thus, CLIP reveals that Nova coordinately regulates a biologically coherent set of RNAs encoding multiple components of the inhibitory synapse, an observation that may relate to the cause of abnormal motor inhibition in POMA.
Self-Assembled Silica-Carbonate Structures and Detection of Ancient Microfossils
Authors: García-Ruiz J. M. , Hyde S. T. , Carnerup A. M. , Christy A. G. , Van Kranendonk M. J. , Welham N. J.
Published: November 2003

We have synthesized inorganic micron-sized filaments, whose microstucture consists of silica-coated nanometer-sized carbonate crystals, arranged with strong orientational order. They exhibit noncrystallographic, curved, helical morphologies, reminiscent of biological forms. The filaments are similar to supposed cyanobacterial microfossils from the Precambrian Warrawoona chert formation in Western Australia, reputed to be the oldest terrestrial microfossils. Simple organic hydrocarbons, whose sources may also be abiotic and indeed inorganic, readily condense onto these filaments and subsequently polymerize under gentle heating to yield kerogenous products. Our results demonstrate that abiotic and morphologically complex microstructures that are identical to currently accepted biogenic materials can be synthesized inorganically.
Understanding climate change risk and vulnerability in northern forest-based communities
Authors: Davidson Debra J , Williamson Tim , Parkins John R
Published: November 2003

Much research attention regarding climate change has been focused on the macrophysical and, to a lesser extent, the macrosocial features of this phenomenon. An important step in mitigation and adaptation will be to examine the ways that climate change risks manifest themselves in particular social localities. Certain social groups may be at greater risk, not solely because of their geographic location in a region of high climate sensitivity but also because of economic, political, and cultural characteristics. Combining the insights of economics and sociology, we provide an ideal-type model of northern forest-based communities that suggests that these communities may represent a particularized social context in regard to climate change. Although scientific research indicates that northern forest ecosystems are among those regions at greatest risk to the impacts of climate change, the social dimensions of these communities indicate both a limited community capacity and a limited potential to perceive climate change as a salient risk issue that warrants action. Five features of forest-based communities describe this context in further detail: (i) the constraints on adaptability in rural, resource-dependent communities to respond to risk in a proactive manner, (ii) the national and international identification of deforestation as a central causal mechanism in the political arena, (iii) the nature of commercial forestry investment planning and management decision-making, (iv) the potential by members of these communities to underestimate the risk associated with climate change, and (v) the multiplicity of climate change risk factors in forest-based communities.
Site temperatures influence seasonal changes in terpene composition in Douglas-fir vegetative buds and current-year foliage
Authors: Nault Jason R
Published: November 2003

Over a 3-year period (19982000), variations in terpene composition was measured in vegetative buds of Douglas-fir (Pseudotsuga menziesii (Mirb.) Franco) from six sites varying in elevation and geographic location with sampling from early spring to midsummer. Eleven terpenes were found in virtually all samples (tricyclene, α-pinene, camphene, sabinene, β-pinene, myrcene, Δ-3-carene, limonene, β-phellandrene, terpinolene, and bornyl acetate) and represented an average of 87% of the total terpenes. In each year, composition of the terpene mix varied significantly (P [Formula: see text] 0.05) for all sites and dates, with some significant site and date interactions. Degree-day accumulations were calculated for all sites and years. Patterns of change in terpene composition between sites, areas, and years were strongly related to the temperature regimes associated with site and year.
INTELLIGENT STATES FOR AN INTERPOLATING ALGEBRA
Authors: ROY B. , ROYCHOUDHURY R.
Published: November 2003

Intelligent states in the sense of field intensity dependent squeezing for a closed and symmetric algebra which interpolates between the Heisenberg Weyl algebra W3 and su(1,1) algebra are constructed. The explicit expressions of these states in terms of Laguerre polynomials are derived and their quantum statistical properties are investigated.
ELECTRONIC STRUCTURE CALCULATIONS FOR PrFe4P12 FILLED SKUTTERUDITE USING EXTENDED HUCKEL TIGHT-BINDING METHOD
Authors: GALVAN DONALD H.
Published: November 2003

To gain insight into the electronic properties of PrFe4P12 filled skutterudite, band electronic structure calculations, total and projected density of states, crystal orbital overlap population and Mulliken population analysis were performed. The energy bands yield a semi-metallic behavior with a direct gap (at Γ) of 0.02 eV. Total and Projected Density of States provided information of the contribution from each orbital of each atom to the total Density of States. Moreover, the bonding strength between some atoms within the unit cell was obtained. Mulliken Population Analysis suggests ionic behavior for this filled skutterudite.