bluuebunny/crossref_metadata_2025 huggingface dataset:
Glucagon-like peptide 1 agonists and the development and growth of pancreatic β-cells
Authors: List James F. , Habener Joel F.
Published: May 2004

Glucagon-like peptide 1 (GLP-1) is an intestine-derived insulinotropic hormone that stimulates glucose-dependent insulin production and secretion from pancreatic β-cells. Other recognized actions of GLP-1 are to suppress glucagon secretion and hepatic glucose output, delay gastric emptying, reduce food intake, and promote glucose disposal in peripheral tissues. All of these actions are potentially beneficial for the treatment of type 2 diabetes mellitus. Several GLP-1 agonists are in clinical trials for the treatment of diabetes. More recently, GLP-1 agonists have been shown to stimulate the growth and differentiation of pancreatic β-cells, as well as to exert cytoprotective, antiapoptotic effects on β-cells. Recent evidence indicates that GLP-1 agonists act on receptors on pancreas-derived stem/progenitor cells to prompt their differentiation into β-cells. These new findings suggest an approach to create β-cells in vitro by expanding stem/progenitor cells and then to convert them into β-cells by treatment with GLP-1. Thus GLP-1 may be a means by which to create β-cells ex vivo for transplantation into patients with insulinopenic type 1 diabetes and severe forms of type 2 diabetes.
Proteomic research: potential opportunities for clinical and physiological investigators
Authors: Nair K. Sreekumaran , Jaleel Abdul , Asmann Yan W. , Short Kevin R. , Raghavakaimal Sreekumar
Published: May 2004

Proteomics is the comprehensive and systematic study of proteins, which are functional molecules. Although proteins are products of gene expression, there are more proteins than genes due to the posttranslational modifications of proteins, making the study of proteins difficult. Protein expression is tissue specific, and its function is modulated by variety of factors, including other proteins, phosphates, sulfates, carbohydrates, and lipids, as well as other metabolites. Because of the dynamic nature of protein expression and posttranslational modifications, identification and quantification of proteins alone are not sufficient to understand functional changes. Emerging technologies will allow investigators to perform a combination of metabolic labeling and identification as well as quantification and measurement of the synthesis rates of a large number of proteins in a tissue. This offers the opportunity to better understand the regulation of tissue functions. Rapid advances in mass spectrometry, protein purification techniques, isotope labeling of proteins, and bioinformatics are likely to improve our understanding of physiological states and altered functions in diseased states. Such mechanistic information will improve the ability to perform early diagnosis of tumors and other diseases and develop prognostic indexes and novel therapies.
Exaggerated 17-hydroxyprogesterone response to intravenous infusions of recombinant human LH in women with polycystic ovary syndrome
Authors: McCartney Christopher R. , Bellows Amy B. , Gingrich Melissa B. , Hu Yun , Evans William S. , Marshall John C. , Veldhuis Johannes D.
Published: May 2004

Studies using pharmacological gonadotropin stimulation suggest that ovarian steroidogenesis is abnormal in the polycystic ovary syndrome (PCOS). We assessed ovarian steroid secretion in response to near-physiological gonadotropin stimuli in 12 ovulatory controls and 7 women with PCOS. A gonadotropin-releasing hormone-receptor antagonist (ganirelix, 2 mg sc) was given to block endogenous LH secretion, followed by dexamethasone (0.75 mg orally) to suppress adrenal androgen secretion. After ganirelix injection (12 h), intravenous infusions of recombinant human LH (0, 10, 30, 100, and 300 IU; each over 8 min) were administered at 4-h intervals in a pseudorandomized (highest dose last) manner. Plasma LH, 17-hydroxyprogesterone (17-OHP), androstenedione, and testosterone were measured concurrently. LH dose-steroid response relationships (mean sex-steroid concentration vs. mean LH concentration over 4 h postinfusion) were examined for each subject. Linear regression of 17-OHP on LH yielded a higher (mean ± SE) slope in PCOS (0.028 ± 0.010 vs. 0.005 ± 0.005, P < 0.05), whereas extrapolated 17-OHP at zero LH was similar. The slopes of other regressions did not differ from zero in either PCOS or controls. We conclude that near-physiological LH stimulation drives heightened 17-OHP secretion in patients with PCOS, suggesting abnormalities of early steps of ovarian steroidogenesis. With the exception of 17-OHP response in PCOS, no acute LH dose-ovarian steroid responses were observed in controls or PCOS. Defining the precise mechanistic basis of heightened precursor responsiveness to LH in PCOS will require further clinical investigation.
Catabolic action of insulin in rat arcuate nucleus is not enhanced by exogenous “tub” expression
Authors: Figlewicz Dianne P. , Zavosh Aryana , Sexton Timothy , Neumaier John F.
Published: May 2004

The central nervous system (CNS) protein “tub” has been identified from the genetically obese “tubby” mouse. Although the native function of tub in situ is not understood, cell-based studies suggest that one of its roles may be as an intracellular signaling target for insulin. In normal animals, insulin acts at the hypothalamic arcuate nucleus (ARC) to regulate energy balance. Here we used a Herpes Simplex viral expression system to evaluate whether tub overexpression in the ARC of normal rats enhances this action of insulin. In chow-fed rats, tub overexpression had no effect on insulin action. In rats fed a high-fat diet snack in addition to chow, simulating the diet of Westernized societies, the body weight regulatory action of insulin was impaired, and tub overexpression further impaired insulin action. Thus an excess of tub at the ARC does not enhance the in vivo effectiveness of insulin and is not able to compensate for the “downstream” consequences of a high-fat diet to impair CNS body weight regulatory mechanisms.
Effects of rosiglitazone on gene expression in subcutaneous adipose tissue in highly active antiretroviral therapy-associated lipodystrophy
Authors: Sutinen Jussi , Kannisto Katja , Korsheninnikova Elena , Fisher Rachel M. , Ehrenborg Ewa , Nyman Tuulikki , Virkamäki Antti , Funahashi Tohru , Matsuzawa Yuji , Vidal Hubert , Hamsten Anders , Yki-Järvinen Hannele
Published: May 2004

Highly active antiretroviral therapy (HAART) has improved the prognosis of human immunodeficiency virus (HIV)-infected patients but is associated with severe adverse events, such as lipodystrophy and insulin resistance. Rosiglitazone did not increase subcutaneous fat in patients with HAART-associated lipodystrophy (HAL) in a randomized, double-blind, placebo-controlled trial, although it attenuated insulin resistance and decreased liver fat content. The aim of this study was to examine effects of rosiglitazone on gene expression in subcutaneous adipose tissue in 30 patients with HAL. The mRNA concentrations in subcutaneous adipose tissue were measured using real-time PCR. Twenty-four-week treatment with rosiglitazone (8 mg/day) compared with placebo significantly increased the expression of adiponectin, peroxisome proliferator-activated receptor-γ (PPARγ), and PPARγ coactivator 1 and decreased IL-6 expression. Expression of other genes involved in lipogenesis, fatty acid metabolism, or glucose transport, such as acyl-CoA synthase, adipocyte lipid-binding protein, CD45, fatty acid transport protein-1 and -4, GLUT1, GLUT4, keratinocyte lipid-binding protein, lipoprotein lipase, PPARδ, and sterol regulatory element-binding protein-1c, remained unchanged. Rosiglitazone also significantly increased serum adiponectin concentration. The change in serum adiponectin concentration was inversely correlated with the change in fasting serum insulin concentration and liver fat content. In conclusion, rosiglitazone induced significant changes in gene expression in subcutaneous adipose tissue and ameliorated insulin resistance in patients with HAL. Increased expression of adiponectin might have mediated most of the favorable insulin-sensitizing effects of rosiglitazone in these patients.
Mitochondrial localization of ERα and ERβ in human MCF7 cells
Authors: Chen Jin Q. , Delannoy Michael , Cooke Carol , Yager James D.
Published: May 2004

We observed previously that estrogen treatment increased the transcript levels of several mitochondrial DNA (mtDNA)-encoded genes for mitochondrial respiratory chain (MRC) proteins and MRC activity in rat hepatocytes and human Hep G2 cells. Others have reported detection of estrogen receptors (ER), ERα and ERβ, in mitochondria of rabbit ovarian and uterine tissue. In this study, we have extended these observations. Using cellular fractionation and Western blot with ERα- and ERβ-specific antibodies, we observed that ERα and ERβ are present in mitochondria of human MCF7 cells and that the mitochondrial ERα and ERβ account for 10 and 18%, respectively, of total cellular ERα and ERβ in 17β-estradiol (E2)-treated MCF7 cells. We also found that E2 significantly enhanced the amounts of mitochondrial ERα and ERβ in a time- and concentration-dependent manner and that these effects are accompanied by a significant increase in the transcript levels of mtDNA-encoded genes, i.e., cytochrome c oxidase subunits I and II. Moreover, we demonstrated that these E2-mediated effects were inhibited by the pure ER antagonist, ICI-182780, indicating the involvement of ERs. Using immunohistochemistry with confocal microscopy and immunogold electron microscopy, we demonstrated that ERα and ERβ are located within the MCF7 cell mitochondrial matrix. Computer analysis identified a putative internal mitochondrial targeting peptide signal within human ERβ, suggesting an inherent potential for ERβ to enter mitochondria. These findings confirm the observations of others and provide additional support for this novel localization of the ERs and for a potentially important role of the ER in the regulation of mtDNA transcription.
Different mechanisms can alter fatty acid transport when muscle contractile activity is chronically altered
Authors: Koonen Debby P. Y. , Benton Carley R. , Arumugam Yoga , Tandon Narendra N. , Calles-Escandon Jorge , Glatz Jan F. C. , Luiken Joost J. F. P. , Bonen Arend
Published: May 2004

We examined whether skeletal muscle transport rates of long-chain fatty acids (LCFAs) were altered when muscle activity was eliminated (denervation) or increased (chronic stimulation). After 7 days of chronically stimulating the hindlimb muscles of female Sprague-Dawley rats, the LCFA transporter proteins fatty acid translocase (FAT)/CD36 (+43%) and plasma membrane-associated fatty acid-binding protein (FABPpm; +30%) were increased ( P < 0.05), which resulted in the increased plasmalemmal content of these proteins (FAT/CD36, +42%; FABPpm +13%, P < 0.05) and a concomitant increase in the LCFA transport rate into giant sarcolemmal vesicles (+44%, P < 0.05). Although the total muscle contents of FAT/CD36 and FABPpm were not altered ( P > 0.05) after 7 days of denervation, the LCFA transport rate was markedly decreased (−39%). This was associated with reductions in plasmalemmal FAT/CD36 (−24%) and FABPpm (−28%; P < 0.05). These data suggest that these LCFA transporters were resequestered to their intracellular depot(s) within the muscle. Combining the results from these experiments indicated that changes in rates of LCFA transport were correlated with concomitant changes in plasmalemmal FAT/CD36 and FABPpm, but not necessarily with their total muscle content. Thus chronic alterations in muscle activity can alter the rates of LCFA transport via different mechanisms, either 1) by increasing the total muscle content of FAT/CD36 and FABPpm, resulting in a concomitant increase at the sarcolemma, or 2) by reducing the plasma membrane content of these proteins in the absence of any changes in their total muscle content.
IGF-I/IGFBP-3 ameliorates alterations in protein synthesis, eIF4E availability, and myostatin in alcohol-fed rats
Authors: Lang Charles H. , Frost Robert A. , Svanberg Elisabeth , Vary Thomas C.
Published: May 2004

Chronic alcohol consumption decreases the concentration of the anabolic hormone IGF-I, and this change is associated with impaired muscle protein synthesis. The present study evaluated the ability of IGF-I complexed with IGF-binding protein (IGFBP)-3 to modulate the alcohol-induced inhibition of muscle protein synthesis in gastrocnemius. After 16 wk on an alcohol-containing diet, either the IGF-I/IGFBP-3 binary complex (BC) or saline was injected two times daily for three consecutive days. After the final injection of BC (3 h), plasma IGF-I concentrations were elevated in alcohol-fed rats to values not different from those of similarly treated control animals. Alcohol feeding decreased the basal rate of muscle protein synthesis by limiting translational efficiency. BC treatment of alcohol-fed rats increased protein synthesis back to basal control values, but the rate remained lower than that of BC-injected control rats. The BC partially reversed the alcohol-induced decrease in the binding of eukaryotic initiation factor (eIF)4E with eIF4G. This change was associated with reversal of the alcohol-induced dephosphorylation of eIF4G but was independent of changes in the phosphorylation of either 4E-BP1 or eIF4E. However, BC reversed the alcohol-induced increase in IGFBP-1 and muscle myostatin, known negative regulators of IGF-I action and muscle mass. Hence, exogenous IGF-I, administered as part of a BC to increase its circulating half-life, can in part reverse the decreased protein synthesis observed in muscle from chronic alcohol-fed rats by stimulating selected components of translation initiation. The data support the role of IGF-I as a mediator of chronic alcohol myopathy in rats.
The Airway Compartment: Chambers of Secrets
Authors: Beck-Schimmer B. , Schimmer R.C. , Pasch T.
Published: May 2004

The adhesion molecule intercellular adhesion molecule-1 (ICAM-1) is known to play a crucial role in lung inflammation such as endotoxin-induced injury. Although ICAM-1 has been characterized on endothelial cells, limited information is available regarding its expression in the epithelial compartment. The present review provides novel views on this aspect.
Proteomic Strategies and Their Application in Studies of Renal Function
Authors: Cutillas Pedro , Burlingame Alma , Unwin Robert
Published: May 2004

Proteomics is a promising new tool for functional genomics. In addition to two-dimensional gel electrophoresis, other methods that are based on liquid chromatography and mass spectrometry are now available to study proteins. In this brief article, we review the strengths and limitations of the proteomic approaches currently available to the researcher, and we provide examples of how proteomics has been, and can in the future be, used to study the kidney.
Parietal Lobe Lesions Disrupt Saccadic Remapping of Inhibitory Location Tagging
Authors: Sapir Ayelet , Hayes Amy , Henik Avishai , Danziger Shai , Rafal Robert
Published: May 2004

Maintaining a coherent percept of the visual scene while eye position continuously changes requires that saccades be accompanied by remapping of the visual environment. We studied saccadic remapping in patients with unilateral lesions in the intraparietal sulcus and healthy controls, using inhibition of return (IOR)—an inhibitory tag that enables efficient visual search. In healthy controls, IOR was found at both retinal and environmental locations of the cue, indicating that the inhibitory tag had been remapped into environmental coordinates. In contrast, right parietal patients demonstrated IOR only at the retinal location of the cue, indicating that the intraparietal sulcus is involved in remapping of the environment after eye movements to afford a stable, environmentally based reference frame. Note that patients did not show environmental IOR in either visual field. These results also suggest that this region may be the neural substrate for encoding inhibitory spatial tags in an environmentally based reference frame.
Two Visual Motion Processing Deficits in Developmental Dyslexia Associated with Different Reading Skills Deficits
Authors: Wilmer Jeremy B. , Richardson Alexandra J. , Chen Yue , Stein John F.
Published: May 2004

Developmental dyslexia is associated with deficits in the processing of visual motion stimuli, and some evidence suggests that these motion processing deficits are related to various reading subskills deficits. However, little is known about the mechanisms underlying such associations. This study lays a richer groundwork for exploration of such mechanisms by more comprehensively and rigorously characterizing the relationship between motion processing deficits and reading subskills deficits. Thirty-six adult participants, 19 of whom had a history of developmental dyslexia, completed a battery of visual, cognitive, and reading tests. This battery combined motion processing and reading subskills measures used across previous studies and added carefully matched visual processing control tasks. Results suggest that there are in fact two distinct motion processing deficits in developmental dyslexia, rather than one as assumed by previous research, and that each of these deficits is associated with a different type of reading subskills deficit. A deficit in detecting coherent motion is selectively associated with low accuracy on reading subskills tests, and a deficit in discriminating velocities is selectively associated with slow performance on these same tests. In addition, evidence from visual processing control tasks as well as self-reports of ADHD symptoms suggests that these motion processing deficits are specific to the domain of visual motion, and result neither from a broader visual deficit, nor from the sort of generalized attention deficit commonly comorbid with developmental dyslexia. Finally, dissociation between these two motion processing deficits suggests that they may have distinct neural and functional underpinnings. The two distinct patterns of motion processing and reading deficits demonstrated by this study may reflect separable underlying neurocognitive mechanisms of developmental dyslexia.
ERP Effects of Subject—Verb Agreement Violations in Patients with Broca's Aphasia
Authors: Wassenaar Marlies , Brown Colin M. , Hagoort Peter
Published: May 2004

This article presents electrophysiological data on on-line syntactic processing during auditory sentence comprehension in patients with Broca's aphasia. Event-related brain potentials (ERPs) were recorded from the scalp while subjects listened to sentences that were either syntactically correct or contained violations of subject-verb agreement. Three groups of subjects were tested: Broca patients (n = 10), nonaphasic patients with a right-hemisphere (RH) lesion (n = 5), and healthy agedmatched controls (n = 12). The healthy, control subjects showed a P600/SPS effect as response to the agreement violations. The nonaphasic patients with an RH lesion showed essentially the same pattern. The overall group of Broca patients did not show this sensitivity. However, the sensitivity was modulated by the severity of the syntactic comprehension impairment. The largest deviation from the standard P600/SPS effect was found in the patients with the relatively more severe syntactic comprehension impairment. In addition, ERPs to tones in a classical tone oddball paradigm were also recorded. Similar to the normal control subjects and RH patients, the group of Broca patients showed a P300 effect in the tone oddball condition. This indicates that aphasia in itself does not lead to a general reduction in all cognitive ERP effects. It was concluded that deviations from the standard P600/SPS effect in the Broca patients reflected difficulties with on-line maintaining of number information across clausal boundaries for establishing subject-verb agreement.
Motor Sequence Complexity and Performing Hand Produce Differential Patterns of Hemispheric Lateralization
Authors: Haaland Kathleen Y. , Elsinger Catherine L. , Mayer Andrew R. , Durgerian Sally , Rao Stephen M.
Published: May 2004

Studies in brain damaged patients conclude that the left hemisphere is dominant for controlling heterogeneous sequences performed by either hand, presumably due to the cognitive resources involved in planning complex sequential movements. To determine if this lateralized effect is due to asymmetries in primary sensorimotor or association cortex, whole-brain functional magnetic resonance imaging was used to measure differences in volume of activation while healthy right-handed subjects performed repetitive (simple) or heterogeneous (complex) finger sequences using the right or left hand. Advanced planning, as evidenced by reaction time to the first key press, was greater for the complex than simple sequences and for the left than right hand. In addition to the expected greater contralateral activation in the sensorimotor cortex (SMC), greater left hemisphere activation was observed for left, relative to right, hand movements in the ipsilateral left superior parietal area and for complex, relative to simple, sequences in the left premotor and parietal cortex, left thalamus, and bilateral cerebellum. No such volumetric asymmetries were observed in the SMC. Whereas the overall MR signal intensity was greater in the left than right SMC, the extent of this asymmetry did not vary with hand or complexity level. In contrast, signal intensity in the parietal and premotor cortex was greater in the left than right hemisphere and for the complex than simple sequences. Signal intensity in the caudal anterior cerebellum was greater bilaterally for the complex than simple sequences. These findings suggest that activity in the SMC is associated with execution requirements shared by the simple and complex sequences independent of their differential cognitive requirements. In contrast, consistent with data in brain damaged patients, the left dorsal premotor and parietal areas are engaged when advanced planning is required to perform complex motor sequences that require selection of different effectors and abstract organization of the sequence, regardless of the performing hand.
Computing and Stability in Cortical Networks
Authors: Latham Peter E. , Nirenberg Sheila
Published: May 2004

Cortical neurons are predominantly excitatory and highly interconnected. In spite of this, the cortex is remarkably stable: normal brains do not exhibit the kind of runaway excitation one might expect of such a system. How does the cortex maintain stability in the face of this massive excitatory feedback? More importantly, how does it do so during computations, which necessarily involve elevated firing rates? Here we address these questions in the context of attractor networks—networks that exhibit multiple stable states, or memories. We find that such networks can be stabilized at the relatively low firing rates observed in vivo if two conditions are met: (1) the background state, where all neurons are firing at low rates, is inhibition dominated, and (2) the fraction of neurons involved in a memory is above some threshold, so that there is sufficient coupling between the memory neurons and the background. This allows “dynamical stabilization” of the attractors, meaning feedback from the pool of background neurons stabilizes what would otherwise be an unstable state. We suggest that dynamical stabilization may be a strategy used for a broad range of computations, not just those involving attractors.
Real-Time Computation at the Edge of Chaos in Recurrent Neural Networks
Authors: Bertschinger Nils , Natschläger Thomas
Published: May 2004

Depending on the connectivity, recurrent networks of simple computational units can show very different types of dynamics, ranging from totally ordered to chaotic. We analyze how the type of dynamics (ordered or chaotic) exhibited by randomly connected networks of threshold gates driven by a time-varying input signal depends on the parameters describing the distribution of the connectivity matrix. In particular, we calculate the critical boundary in parameter space where the transition from ordered to chaotic dynamics takes place. Employing a recently developed framework for analyzing real-time computations, we show that only near the critical boundary can such networks perform complex computations on time series. Hence, this result strongly supports conjectures that dynamical systems that are capable of doing complex computational tasks should operate near the edge of chaos, that is, the transition from ordered to chaotic dynamics.
Walking with and Without Walking: Perception of Distance in Large-Scale Urban Areas in Reality and in Virtual Reality
Authors: Popp Michael M. , Platzer Edna , Eichner Matthias , Schade Marion
Published: May 2004

The perception of distance when walking through an urban area depends on several factors. In addition to knowledge of the physical length of a route based on known parameters such as the walking speed and the time or number of steps, this paper also discusses external factors such as the visual appearance and details of the route and internal factors such as the physiological effort or emotional states during the walk. It is not clear which of the latter factors are stored in memory and are used to estimate a perceived distance. The hypothesis of distance estimation on the basis of perceived and remembered effort is held by several researchers. The reported experiments tried to clarify that question with research in actual reality and virtual reality. In doing so, we were able to separate the component of real walking from other sources that possibly affect distance estimation. In addition, this work demonstrates the power of experiments in VR compared with equivalent experiments in reality.
Toward High-Fidelity Telepresence in Space and Surgery Robotics
Authors: Reintsema Detlef , Preusche Carsten , Ortmaier Tobias , Hirzinger Gerd
Published: May 2004

High-fidelity telepresence is considered to be a key subject for the development of advanced space and surgery robotic systems. The emphasis of this paper are the key challenges like multimodal data servicing, bilateral and shared control concepts, and kinesthetic feedback devices. These technologies are the basic principles in the development of advanced space and surgery applications. Beside these technologies, advanced mechatronic systems are required as shown within this paper. The applicability of the high-fidelity telepresence concept is explored by selected space and surgery scenarios.
Interactive Simulation of Complex Audiovisual Scenes
Authors: Doel Kees van den , Knott Dave , Pai Dinesh K.
Published: May 2004

We demonstrate a method for efficiently rendering the audio generated by graphical scenes with a large number of sounding objects. This is achieved by using modal synthesis for rigid bodies and rendering only those modes that we judge to be audible to a user observing the scene. We show how excitations of modes can be estimated and inaudible modes eliminated based on the masking characteristics of the human ear. We describe a novel technique for generating contact events by performing closed-form particle simulation and collision detection with the aid of programmable graphics hardware. The effectiveness of our system is shown in the context of suitably complex simulations.
Old Efforts at New Uses: A Brief History of Chemurgy and the American Search for Biobased Materials
Authors: Finlay Mark R.
Published: May 2004

The American search for biobased and renewable raw materials has a long history of intermittent success and frustration. This article traces the history of the chemurgy movement‐a precursor to what are now sometimes called agricultural “new uses” initiatives‐from its context of the 1920s through its emergence as a political force in the mid‐1930s, when chemurgy offered a strategy for industries and governments interested in reviving the agricultural economy and reducing dependence upon foreign sources of industrial raw materials. Chemurgists put pressure upon the U.S. Department of Agriculture to devote greater attention to crop utilization research, efforts that were operational in time to make important contributions to the U.S. economy during World War II. This article devotes considerable attention to the postwar era, a period not discussed in most histories of chemurgy. The article concludes with a tentative assessment of issues that caused chemurgy to falter in the past as well as precautionary lessons for the contemporary study of biobased materials.
Comparing the Land Requirements, Energy Savings, and Greenhouse Gas Emissions Reduction of Biobased Polymers and Bioenergy
Authors: Dornburg Veronika , Lewandowski Iris , Patel Martin
Published: May 2004

This study compares energy savings and greenhouse gas (GHG) emission reductions of biobased polymers with those of bioenergy on a per unit of agricultural land‐use basis by extending existing life‐cycle assessment (LCA) studies. In view of policy goals to increase the energy supply from biomass and current efforts to produce biobased polymers in bulk, the amount of available land for the production of nonfood crops could become a limitation. Hence, given the prominence of energy and greenhouse issues in current environmental policy, it is desirable to include land demand in the comparison of different biomass options. Over the past few years, numerous LCA studies have been prepared for different types of bio‐based polymers, but only a few of these studies address the aspect of land use. This comparison shows that referring energy savings and GHG emission reduction of biobased polymers to a unit of agricultural land, instead of to a unit of polymer produced, leads to a different ranking of options. If land use is chosen as the basis of comparison, natural fiber composites and thermoplastic starch score better than bioenergy production from energy crops, whereas polylactides score comparably well and polyhydroxyalkaonates score worse. Additionally, including the use of agricultural residues for energy purposes improves the environmental performance of bio‐based polymers significantly. Moreover, it is very likely that higher production efficiencies will be achieved for biobased polymers in the medium term. Biobased polymers thus offer interesting opportunities to reduce the utilization of nonrenewable energy and to contribute to GHG mitigation in view of potentially scarce land resources.
Life‐Cycle Assessment of Mineral and Rapeseed Oil in Mobile Hydraulic Systems
Authors: McManus Marcelle C. , Hammond Geoffrey P. , Burrows Clifford R.
Published: May 2004

The use of rapeseed oil in mobile hydraulic systems has become more widespread over recent years. This is because of concern about the environment in which the systems work and the perceived benefit of using such fluids. This article examines the major segments of the life cycle of mineral and rapeseed oil as used in mobile hydraulic systems, with case studies of a forestry harvester and a road sweeper. It shows that the systems running on rapeseed oil are not necessarily better for the environment. Many of the environmental issues examined in the study were affected more negatively by the use of rapeseed oil than mineral oil. The main exception to this was greenhouse gas emissions, which are consistently higher for systems using mineral oil because of the use of fossil resources.

This study examines the production of the machinery, the oils, and their use throughout the machines' lives. The poor environmental performance of the rapeseed oil is due mainly to its poor performance in the field. This is because it does not respond as well to high pressure and temperature as mineral oil, causing it to need more frequent replacement during use. This, in turn, influences the definition of the functional unit used in the life‐cycle assessment that was conducted. Also, the rapeseed oil has more corrosive qualities than the mineral oil, and more hydraulic components need replacing during the life of a machine running on rapeseed oil than one running on mineral oil.
A Sustainability Assessment of a Biolubricant
Authors: Cunningham Bryony , Battersby Nigel , Wehrmeyer Walter , Fothergill Catriona
Published: May 2004

A sustainability matrix has been developed at Shell Global Solutions to show the environmental, social, and economic impacts of a product. The approach aims to be quicker and more cost‐effective than a conventional life‐cycle assessment by focusing on specific areas of concern through the product life cycle and then comparing products by scaling their impacts relative to one another. It provides a way of making qualitative and quantitative assessment that gives a depth to the assessment beyond data analysis. The tool includes subjective judgment, which tends to reflect current thinking in the company. Once the tool has been fully tested on all product types, the indicators that are central to the process will be assessed by external stakeholders. This article describes the development of the sustainability assessment tool and presents an example that compares the sustainability of a biolubricant (an “environ‐mentally acceptable” hydraulic fluid meeting Swedish Standard SS 15 54 34) with that of a conventional mineral‐oil‐based product. The tool provides a quick decision‐making instrument to help Shell decide which products should be marketed for the business to continue on a sustainable path. The tool also provides a more detailed level of information if a more thorough assessment is necessary.
From Apartheid to the New Dispensation: Evangelicals and the Democratization of South Africa1
Authors: Balcomb Anthony
Published: May 2004

In this article, I attempt to distinguish between five responses to the political situation in South Africa made by evangelicals before and after the end of apartheid in April 1994. I characterize the adherents of these positions as the conservatives, the pragmatists, the protagonists of the Third Way, the protagonists of the 'alternative' community and the liberationists. I then attempt to demonstrate their influence in the transformation of South African society towards democracy by undertaking a series of typological case studies of prominent representatives of these positions. In the process, I attempt to unpack some of the theological and political thinking that underlies and explains each position.
Discontinuity and the Discourse of Conversion
Authors: Engelke Matthew
Published: May 2004

This paper focuses on the conversion narrative of a man in the Johane Masowe weChishanu Church, an apostolic church in Zimbabwe. Taking up recent discussions within anthropology on Pentecostal and charismatic churches, the author shows how apostolics talk about conversion as a distinct break with 'African custom'. It is argued that anthropologists of religion need to take such narratives of discontinuity seriously because they allow us to understand better the dynamics of religious change.
'One Day we Will Sing in God's Home': Hymns and Songs Sung in the Anglican Church in North-East Congo (drc)
Authors: Wild-Wood Emma , Wood Peter
Published: May 2004

'Songs preach a lot' claim members of the Anglican Church in North-East Congo (DRC). This article analyses what these songs preach and how they convey their message. It examines the theology of the texts as sung in their musical and social context. The songs fall into two broad categories: western hymns translated by missionaries and contemporary songs often composed locally or nationally. They have different but overlapping theologies and functions within worship. Heaven emerges as a central motif in both categories, presenting an eschatological oral theology, which offers comfort, escape and social comment.
Optimizing Dose Selection with Modeling and Simulation: Application to the Vasopeptidase Inhibitor M100240
Authors: Pfister Marc , Martin Nancy E. , Haskell Lloyd P. , Barrett Jeffrey S.
Published: May 2004

Dual inhibition of neutral endopeptidase 24.11 (NEP) and angiotensin‐converting enzyme (ACE) has gained increasing interest in the treatment of hypertension, heart failure, and renoprotection. Specifically, M100240, the thioester of the dual ACE/NEP inhibitor MDL100,173, has been evaluated in the management of hypertension. A model‐based analysis, including simulations, was employed to characterize the relationship between individual M100240 drug exposure and neurohormonal response and to optimize the dose selection for future clinical studies. Sixty‐two healthy subjects and 189 hypertensive patients were studied after oral once‐daily administration of 2.5, 5, 10, 25, or 50 mg M100240. Pharmacokinetic‐biomarker and blood pressure response models were fitted to the data with the computer program NONMEM. A direct inhibitory Emax model adequately described the relationship between MDL100,173 concentration and ACE activity. No clear concentration or dose‐dependent NEP or blood pressure responses were evident. Given a target 90% ACE inhibition, simulation reveals that (1) 50 mg M100240 once daily produces adequate ACE inhibition 24 hours postdose in only 20% of subjects, and (2) higher and/or more frequent doses on the order of 25 mg three times daily or 50 mg twice daily are required to achieve the target ACE inhibition in at least 50% of patients over 24 hours. Insufficient blood pressure—lowering effects were observed in healthy subjects and hypertensive patients due to inadequate ACE and NEP inhibition with once‐daily oral doses of up to 50 mg of M100240. Divided doses might provide target ACE inhibition in more patients.
Kinetics and EEG Effects of Midazolam during and after 1‐Minute, 1‐Hour, and 3‐Hour Intravenous Infusions
Authors: Greenblatt David J. , Ehrenberg Bruce L. , Culm Kerry E. , Scavone Joseph M. , Corbett Kathleen E. , Friedman Hylar L. , Harmatz Jerold S. , Shader Richard I.
Published: May 2004

The objective of this study was to evaluate the kinetics and dynamics of midazolam when administered by three different infusion schemes, using electroencephalography to measure pharmacodynamic effects. In a three‐way crossover study, 8 volunteers received midazolam (0.1 mg/kg) by constant‐rate intravenous infusion. The durations of midazolam infusions for the three trials were 1 minute, 1 hour, and 3 hours. Plasma midazolam concentrations and electroencephalographic (EEG) activity in the 13‐ to 30‐Hz range were monitored for 24 hours. Based on separate analysis of each subject‐trial, mean values for volume of distribution and distribution or elimination half‐life did not significantly vary. Central compartment volume and clearance differed among the three midazolam infusion trials; however, the magnitude of change was small. EEG activity in the 13‐ to 30‐Hz range significantly increased for all three midazolam infusion trials. Plots of midazolam plasma concentration versus pharmacodynamic EEG effect for the 1‐hour and 3‐hour infusion trials did not reveal evidence of either counterclockwise or clockwise hysteresis. Plots from the 1‐minute infusion trial demonstrated counterclockwise hysteresis, consistent with an equilibration effect‐site delay. This was incorporated into a kinetic‐dynamic model in which hypothetical effect‐site concentration was related to pharmacodynamic EEG effect via the sigmoid Emax model. Analysis of all three infusion trials together yielded the following mean estimates: maximum EEG effect, 16.3% over baseline; 50% maximum effective concentration, 31 ng/mL; and an apparent rate constant for drug disappearance from the effect compartment which approached infinity. Despite the delay in effect onset during the 1‐minute midazolam infusion, midazolam infusions in duration of up to 3 hours produce CNS sedation without evidence of tolerance.
Disease modifying agent related skin reactions in multiple sclerosis: prevention, assessment, and management
Authors: Frohman E M , Brannon K , Alexander Sherry , Sims D , Phillips J T , O'Leary S , Hawker K , Racke M K
Published: May 2004

Background: The objective for this article is to highlight some of the adverse skin manifestations associated with injectable disease modifying therapy for multiple sclerosis (MS). Early identification and intervention can often lead to minimal consequences and prolonged patient tolerance and compliance with these agents. A t the University of Texas Southwestern Medical C enter at Dallas and Texas Neurology in Dallas we actively follow appro ximately 5000 MS patients. The majority of our patients with relapsing-remitting MS (RRMS) or secondary progressive MS (SPMS) are treated with one of the currently available disease modifying agents (DMA s). O ur experience with these patients, and the challenges they face in continuing long-term treatment, constitutes the basis of our proposed treatment strategies. Conclusion: Skin reactio ns in response to injectable DMA therapy in MS are generally mild. However, some reactio ns can evolve into potentially serious lesions culminating in infection, necro sis, and in some circumstances requiring surgical repair.
Elevated aminotransferases during treatment with interferon-beta for multiple sclerosis: actions and outcomes
Authors: Tremlett Helen L , Oger Joel
Published: May 2004

The authors report further analysis of a six-year retrospective chart review of multiple sclerosis (MS) patients prescribed interferon-beta (IFNB) in British C olumbia, C anada. A ctions and outcomes taken when 284/835 (34%) of the patients developed de novo elevated aminotransferases are presented; 239/284 (84%) of patients were continued on treatment despite these elevations; 216/246 (88%) of patients reaching grade 1 toxicity (greater than the upper limit of normal) continued IFNB treatment; of these, 167/216 (77%) returned to within normal limits. O f the 22/29 (76%) reaching grade 2 toxicity (> 2.5 times the upper limit of normal) and continuing treatment, 14/22 (64%) returned to within the normal range. O ne of the nine patients reaching grade 3 toxicity (> 5 times the upper limit of normal) was allowed continue treatment and their aminotransferase levels returned to within normal limits. However, one patient reaching grade 3 toxicity went on to develop liver failure (previously reported).
The pathogenesis of multiple sclerosis: is it really a primary inflammatory process?
Authors: Maggs F G , Palace J
Published: May 2004

The patho genesis of multiple sclerosis (MS) remains unknown. A lthough inflammation, demyelination and axonal injury are all involved, the primary patho genic process is not clear. In this paper we challenge the hypothesis that MS is a primary inflammatory condition, and suggest that axonal damage may occur independently.
An unusual variant of the dorsal midbrain syndrome in MS: clinical characteristics and pathophysiologic mechanisms
Authors: Frohman Elliot M , Dewey Richard B , Frohman Teresa C
Published: May 2004

Patients with MS exhibit a broad diversity of ocular motor syndromes. We describe a patient with relapsing-remitting MS who developed an unusual variation of the dorsal midbrain syndrome, character ized by monocular convergent-retraction nystagmus in the right eye, accompanied by divergent-retraction nystagmus in the fellow eye upon attempted upward gaze. Examination also revealed a skew deviation with a left hyperdeviation and severe adductio n limitation in the left eye during attempted right gaze. We propose that a left INO accounted for the inability of the left eye to adduct (and result in convergent-retraction) during attempted upward saccades. We consider the patho physiologic mechanisms responsible for our observations and review important details of the dorsal midbrain ocular motor circuitr y.
Xenopus U3 snoRNA docks on pre-rRNA through a novel base-pairing interaction
Authors: BOROVJAGIN ANTON V. , GERBI SUSAN A.
Published: May 2004

U3 small nucleolar RNA (snoRNA) is essential for rRNA processing to form 18S ribosomal RNA (rRNA). Previously, it has been shown that nucleolin is needed to load U3 snoRNA on pre-rRNA. However, as documented here, this is not sufficient. We present data that base-pairing between the U3 hinges and the external transcribed spacer (ETS) is critical for functional alignment of U3 on its pre-rRNA substrate. Additionally, the interaction between the U3 hinges and the ETS is proposed to serve as an anchor to hold U3 on the pre-rRNA substrate, while box A at the 5′ end of U3 snoRNA swivels from ETS contacts to 18S rRNA contacts. Compensatory base changes revealed base-pairing between the 3′ hinge of U3 snoRNA and region E1 of the ETS in Xenopus pre-rRNA; this novel interaction is required for 18S rRNA production. In contrast, base-pairing between the 5′ hinge of U3 snoRNA and region E2 of the ETS is auxiliary, unlike the case in yeast where it is required. Thus, higher and lower eukaryotes use different interactions for functional association of U3 with pre-rRNA. The U3 hinge sequence varies between species, but covariation in the ETS retains complementarity. This species-specific U3-pre-rRNA interaction offers a potential target for a new class of antibiotics to prevent ribosome biogenesis in eukaryotic pathogens.
A novel partial modification at C2501 in Escherichia coli 23S ribosomal RNA
Authors: ANDERSEN THOMAS EMIL , PORSE BO TORBEN , KIRPEKAR FINN
Published: May 2004

Escherichia coli is the best-characterized organism with respect to posttranscriptional modifications of its ribosomal RNA (rRNA). It is presently believed that all the modified nucleotides have been identified, primarily on the basis of two detection methods; modification-induced inhibition of the enzyme reverse transcriptase or analysis by combined HPLC and electrospray ionization mass spectrometry. Comparison of data from these different approaches reveals a disagreement regarding modification of C2501 in E. coli 23S rRNA. A. Bakin and J. Ofengand previously reported the detection of a modification at this site based on a reverse transcriptase assay. J.A. McCloskey and coworkers could not confirm the existence of such a modification using an electrospray ionization mass spectrometry approach. C2501 is therefore generally considered unmodified. We have used a strategy involving isolation of a specific rRNA fragment from E. coli 23S rRNA followed by Matrix Assisted Laser Desorption/Ionization mass spectrometry and tandem mass spectrometry to investigate this controversy. Our data reveal a novel 16-Da partial modification at C2501. We believe that the data reported here clarify the above discrepancy, because a minor partial modification detected in a reverse transcriptase assay would not necessarily be detected by the original mass spectrometry approach. The level of modification was furthermore monitored in different growth situations, and we found a significant positive regulation in stationary phase cells. C2501 is universally conserved and implicated in structure folds very close to the catalytic center of the ribosome. Moreover, several antibiotics bind to nucleotides in this region, which altogether make a modification at this site interesting.