bluuebunny/crossref_metadata_2025 huggingface dataset:
Implementing the Online Learning Community in Africa: A Unisa Case Study
Authors: Heydenrych  , Higgs  , van Niekerk
Published: March 2004

Recent global occurrences are significantly affecting institutions of higher education, particularly on the continent of Africa. In addition, the process of the democratization of education has inevitably led to the explosive demands by the citizens of the different African countries for open admission to institutions of higher education. Against this background this article discusses recent developments at the University of South Africa (UNISA) which have been concerned with the adoption of online distance and open learning approaches in order to achieve greater accessibility and the massification of educational products. This is especially pertinent during this era of technology-driven educational innovation, so as to make university programmes not only accessible but also relevant to the needs and aspirations of African communities.
Pedagogical Issues and Gender in Cyberspace Education: Distance Education in South Africa
Authors: Trevor Sehoole Chika , Moja Teboho
Published: March 2004

The purpose of this paper is to analyse the pedagogical and gender issues embedded in distance and cyberspace education. Pedagogical issues to be addressed relate to access, teaching and learning, quality, and research within distance and cyberspace education. The paper will further analyse the gender dimension in cyberspace education in South Africa. Our paper limits itself to cyberspace teaching and learning as a process that takes place using the Internet or the World Wide Web, or uses some digital information and communications technology (ICT). We understand ICT to be a broad concept that includes all forms of electronic communications in both digital and analogue forms. Pedagogical issues in this paper are covered in a broader context, but our analyses of gender issues is limited to cyberspace education. Some literature refers to latter modes of learning as "e-learning" (Bates 2001). Different people have defined the concept, and the more common definition is that cyberspace is the total interconnectedness of human beings through computers and telecommunications without regard to physical geography. William Gibson is credited with inventing or popularising the concept in his novel.
The Chances for Success of the Francophone Centers for Distance Education of the GDLN Network: The Case of the Centre d'Education à Distance de Côte d'Ivoire
Authors: Yao Kouassi
Published: March 2004

The Centers of Distance Education of francophone Africa in Benin, Côte d'Ivoire, and Senegal were set up under a financial and educational agreement with the World Bank. They were inaugurated on June 21, 2000, at the same time as four other centers in English-speaking Africa and eight others on other continents (Appendix 1). Since September 2003, Mauritania has had its own center, thus increasing the number of centers in French-speaking African countries to four. As of November 2003, more than 60 centers were affiliated with the Global Development Learning Network (GDLN). It has known start-up difficulties because of the socioeconomic environment caused the sociopolitical crisis from December 1999 to the civil war in September 2002. It needs a re-adaptation of its missions by public authorities in order to realize its first mission, which is to improve the capabilities of a large number of government executives and decision-makers at a minimal cost. The strategies and educational approach used at the Center are new methods and tools, precursors of what will be used in the education of tomorrow. In this article, we will briefly present the history of the creation of the Global Development Learning Network (GDLN), and then I will draw up a diagnostic account of the two years' functioning of the CED-CI. Finally, I will give an outline for its future growth.
Higher Education Reform: Challenges towards a Knowledge Society in Malaysia
Authors: Kamogawa Akiko
Published: March 2004

The Malaysian government regards highly skilled human capital as the nucleus of a knowledge-based economy and has been attempting to reform higher-educational policies in both the public and private sectors since the mid-1990s. The research reported here seeks to evaluate higher-educational policy reform as it relates to the development of human resources in an era of information and communication technologies (ICT). This research has three goals: first, to determine how Malaysian higher-educational policies have changed by looking at socioeconomic backgrounds; second, to examine case studies of the Malaysia Multimedia University (MMU), Malaysia National University (UKM), and University Malaysia Sarawak (Unimas); and third, to discuss whether ICT is affecting access and course selection in higher education in terms of gender equality. The analysis reported here concludes that the new challenges facing Malaysia offer possibilities not only for bridging the digital divide, in some aspects, nationally, but also for Malaysia to emerge as fundamental to a South-South Corporation and as a Center of Excellence internationally. It will be pointed out how, and to what extent, the government of Malaysia should reconceptualize the Malaysia Super Corridor project (MSC) in order to become a fully developed nation, equipped as a knowledge society.
Partnership in Higher Education in Africa: Communications Implications beyond the 2000s
Authors: Sy Jacques Habib
Published: March 2004

To date, the possibilities for African countries to use information and communication technologies to respond to the challenges and the demand of higher education have been limited. An assessment and analysis of the development, state, and usage of telecommunications in Africa constitute in fact an indication of Africa's overall marginalization in the global system. Communication technologies do not operate independently of the global economic system, which is characterized by structural inequality. Various initiatives devised by governments and development agencies to address the effective and productive integration of telecommunications technology into the educational system have been hindered by the contextual and structural impediments to harnessing and fulfilling their promise, especially for higher education. The paper explores innovative and multi-stakeholder partnership strategies to enhance the development and relevance of new telecommunications technologies to the African education system, especially higher education, for long-term and rooted socioeconomic development.
Appropriate care: the position of the physician
Authors: Gevers
Published: March 2004

No Abstract
Trainee doctors in the UK, and the EC working time directive: a note on stress and working time
Authors: Finch
Published: March 2004

No Abstract
A. Court of Justice of the European Communities
Authors: Cambré
Published: March 2004

No Abstract
Self-Determination, Privacy, and the Right to Die. A Comparative Law Analysis (Germany, United States of America, Japan)
Authors: Meisel  , Koch  , Bernat
Published: March 2004

No Abstract
Emerging legislation in Europe on the legal status of advance directives and medical decision-making with respect to an incompetent patient ('living-wills')
Authors: Nys
Published: March 2004

No Abstract
"Post mortem insemination" in Norway - some legal aspects
Authors: Warberg
Published: March 2004

No Abstract
Retrospective evaluation of response to epoetin alfa in patients with hematologic disorders
Authors: M Kolesar Jill , Duren Betsy A , Baranski Bruce G
Published: February 2004

Study objectives. To evaluate the impact of epoetin therapy in patients with hematologic malignancies and myelodysplasias (MDS) on hemoglobin (Hb) response, transfusion requirements and to evaluate factors, such as endogenous erythropoietin levels and serum creatinine that predict response to epoetin therapy.

Methods. Inpatient and outpatient pharmacy records were analysed to identify patients with hematological disorders receiving epoetin therapy. No patients were receiving treatment with chemotherapy. Baseline and final Hb levels and transfusion requirements were analysed and factors predicting response to epoetin were evaluated.

Results. The mean baseline Hb increased from 9.9 g/dL (91.09) to 12.1 g/dL (91.84) for a mean Hb increase of 2.81 g/dL (P 5 3.3 3 102 12) and 29 of 35 patients experienced clinical benefit to the epoetin. Overall, the mean transfusion burden fell from 0.94 units of packed red blood cells per month to 0.38 units/month (P 5 0.034 by paired t-test) at the end of the evaluation period. When measured by percentage of patients requiring transfusions, 42% had a transfusion the month prior to receiving epoetin, where as only 11% required transfusions while receiving epoetin. The mean endogenous erythropoietin was 51.2 IU/L (n 5 25) in the patients who responded to epoetin and 129 IU/L (n 5 2) in the nonresponder group (P 5 0.012), although two individuals with endogenous erythropoetin levels greater than 200 IU/L responded to epoetin. Thirteen of 14 patients with MDS in this series responded to epoetin, and the only patient not responding was progressing to AML.

Conclusions. Epoetin is effective in improving anemia in patient’s with hematological malignancies not receiving chemotherapy. While the numbers in this retrospective evaluation are small, it appears that patients with low endogenous erythropoetin levels and high serum creatinine are most likely to respond; a relationship that could be explored in future larger and prospective evaluations.
Stability and compatibility of the investigational antimetastatic ruthenium complex NAMI-A in infusion systems and its hemolytic potential
Authors: Bouma Marjan , Nuijen Bastiaan , Challa Eric E , Sava Gianni , Flaibani Antonella , Bult Auke , Beijnen Jos H
Published: February 2004

NAMI-A (imidazolium trans-imidazole dimethylsulfoxide tetrachlororuthenate (III)) is a novel antimetastatic ruthenium complex currently undergoing Phase I clinical trials. It is pharmaceutically formulated as a lyophilized product to be reconstituted and diluted before infusion. The aim of this study was to determine the reconstitution and dilution fluid of choice, and to investigate the stability and compatibility of NAMI-A in solution under different storage conditions and with several container materials. Furthermore, the hemolytic potential and buffer capacity of NAMI-A infusion solution were investigated in vitro. Normal saline or Water for Injections (WfI) can be used for reconstitution of NAMI-A, and the reconstituted solution should be diluted with normal saline to infusion concentration immediately after dissolution if stored at room temperature (1 20 - 258C), but can be stored for up to 48 hours at refrigerated conditions (1 2 - 88C). Infusion solutions can be stored for a maximum of four hours at room temperature or 24 hours at refrigerated conditions before administration to the patient. The infusion solutions can be prepared in either glass or PVC containers, although for practical reasons PVC containers are recommended. The infusion solutions are compatible with a PVC infusion system consisting of a PVC container, PVC infusion line, and needle. Furthermore, NAMI-A infusion solutions have a low buffer capacity and do not cause hemolysis in vitro. Therefore, no pain or hemolysis upon infusion of NAMI-A in the clinical setting is expected.
Introduction
Authors: LEDERHENDLER ISRAEL I.
Published: March 2004

Abstract: Advances in the treatment of mental illness depend, in part, on the elimination of barriers to the use of new basic research findings. Some of the barriers originate in the different research perspectives adopted by clinical and basic researchers. Clinical research is driven by the need to recruit and examine classes of individuals, and so the conceptual framework focuses largely on categories of disorders. Basic researchers, including psychologists and behavioral neuroscientists, investigate fundamental features of behavior such as emotion regulation, attention, or arousal; therefore, disorders are commonly approached from a “dimensional” framework. In the broadest sense dimensions are those features that are common to multiple disorders. Categories are an effort to draw distinctions among disorders. The differences between these frameworks, and the perspectives held among clinicians and basic scientists, are not dichotomous. Many clinicians investigate fundamental aspects of pathophysiology and behavior that apply to multiple disorders, and many basic researchers are developing animal “models” of categorical disorders. It is timely and important to examine these approaches critically, and to work toward formulating perspectives that capture the strengths of each group of researchers so that their common goal of translating research findings into treatments for childhood mental health disorders is strengthened.
Can We Develop a Neurobiological Model of Human Social—Emotional Development?
Authors: NELSON CHARLES A.
Published: March 2004

Abstract: After summarizing the main points raised in articles by Kaslow et al. and Plotsk, a number of questions that derive from these authors' work are listed. Additional questions are then posed, the answers to which will likely facilitate one's ability to translate animal models of child psychopathology into human terms. After summarizing the various advantages and disadvantages to models using mice, rats, and monkeys, several examples of recent research that have attempted to meld animal models with human studies are described.
Expression and role of PDGF-BB and PDGFR-β during testis morphogenesis in the mouse embryo
Authors: Puglianiello Antonella , Campagnolo Luisa , Farini Donatella , Cipollone Daria , Russo Mario A. , Siracusa Gregorio
Published: March 2004

The role played by PDGF in testis morphogenesis is still incompletely understood. The present study investigates the expression and potential role of platelet-derived growth factor-BB (PDGF-BB) and its receptor, PDGF receptor β (PDGFR-β), during mouse testis cord formation, and the possibility that the growth factor may be involved in the migration to the gonad of mesenchymal cells of mesonephric origin. Studies from this laboratory have previously shown that mesenchymal cells that migrate from the mesonephros into the gonad, to form peritubular myoid cells and most of the intertubular cells, can be identified by the presence on their surface of the p75 neurotrophin receptor (p75NTR), and can be isolated to near-purity by immunomagnetic selection with anti-p75NTR antibody. We show here that mesonephric p75NTR(+) cells also bear the PDGFR-β, and are able to migrate and proliferate in vitro in response to PDGF-BB. PDGF-BB is expressed at higher levels in male than female developing gonads, suggesting a role for this factor in testis development. Such a role is further supported by the observation that addition of PDGF-BB to serum-free medium is sufficient to allow organ-cultured male 11.5 days post-coitum urogenital ridges to form testis cords. Finally, we show that mesonephric cell motility and growth induced by exposure to PDGF-BB involve mitogen-activated protein kinases (MAPK) and phosphatidylinositol-3 kinase (PI3-K) pathways, as MAPK inhibitor U0126 and PI3K inhibitor Ly294002 inhibit migration and proliferation in vitro assays. The present findings support the hypothesis that the PDGF/PDGFR system plays a key role in testis morphogenesis in the mouse embryo.
The sting at the end of the tail: Damaging winds associated with extratropical cyclones
Authors: Browning K. A.
Published: March 2004

Strong surface winds often accompany the low‐level jets that occur along the cold fronts of extratropical cyclones, but there is evidence that the strongest surface winds occur in a distinctly different part of a certain class of cyclone. The most damaging extratropical cyclones go through an evolution that involves the formation of a bent‐back front and cloud head separated from the main polar‐front cloud band by a dry slot. When the cyclone attains its minimum central pressure, the trailing tip of the cloud head bounding the bent‐back front forms a hook which goes on to encircle a seclusion of warm air. The most damaging winds occur near the tip of this hook—the sting at the end of the tail.

Observations of the Great Storm of October 1987 in south‐east England are re‐examined in some detail to study this phenomenon. The cloud head is shown to have a banded structure consistent with the existence of multiple mesoscale slantwise circulations. Air within these circulations leaves the hooked tip of the cloud head (and enters the dry slot) much faster than the rate of travel of the cloud‐head tip, implying rapid evaporation and diabatic cooling immediately upwind of the area of damaging surface winds. The circumstantial evidence from the observational study leads one to hypothesize that the mesoscale circulations and the associated evaporative heat sinks may play an active role in strengthening the damaging winds. Regardless of how important this role may be, the evolution of the cloud pattern seen in satellite imagery is a useful tool for nowcasting the occurrence and location of the worst winds. Copyright © 2004 Royal Meteorological Society
On the existence of multiple climate regimes
Authors: Stephenson D. B. , Hannachi A. , O'Neill A.
Published: March 2004

New techniques are presented for testing the three main hypotheses about the probability distribution of the climate system: multinormal (single regime), unimodal but not multinormal (single regime), and multimodal (multiple regimes). Rather than searching for evidence that confirms the multimodal hypothesis expected from the chaos and other strongly nonlinear paradigms, our strategy is to try and reject the simplest single‐regime hypothesis of multinormality expected for aggregate indices of many local weather degrees of freedom. Concerning multiple climate regimes in the northern hemisphere, we find no strong evidence in the available monthly mean reanalysis data for rejecting the single‐regime multinormal hypothesis in favour of the multimodal hypothesis. A simple non‐parametric method is presented for transforming state space into a more homogeneous probability space that makes regimes easier to identify. A spatial point process test is used in this space to demonstrate that the hemispheric clusters are not significantly different to what could be expected from sampling a unimodal distribution. Based on the observed data, the single‐regime multinormal hypothesis can not be rejected at the 5% level of significance and so provides the simplest useful model for the probability distribution for the northern hemisphere geopotential‐height field. Copyright © 2004 Royal Meteorological Society
Föhn flow and stable air mass in the Rhine valley: The beginning of a MAP event
Authors: Beffrey Guillaume , Jaubert Genevieve , Dabas Alain
Published: March 2004

The föhn event of the 8th Intensive Observation Period (20–21 October 1999) of the Mesoscale Alpine Programme is examined at small scale with the help of both instrumental data (especially from a ground‐based Doppler lidar) and of high‐resolution simulation performed with the non‐hydrostatic model meso‐NH. The three‐dimensional characteristics of the flow in the Rhine valley at the beginning of the event are studied. Special attention is given to the interaction between the föhn and a stable air mass, whose presence drives the penetration of the warm and turbulent föhn air to the ground. A quantification of the simulated features of the flow is given in terms of mass budgets over the target area, and a three‐dimensional picture representing the arrival of the föhn air in the Rhine valley area is proposed. Copyright © 2004 Royal Meteorological Society
Air–sea exchange of sensible heat over the Baltic Sea
Authors: Larsén Xiaoliguo , Smedman Ann‐Sofi , Högström Ulf
Published: March 2004

The exchange of sensible heat at the sea surface has been studied with the aid of a comprehensive dataset from the marine site Östergarnsholm in the Baltic Sea, with additional data from another site in the Baltic Sea, Nässkär. The measurements include turbulent fluxes at about 10 m above the water surface, profiles of temperature and wind data at several levels on towers, sea surface temperatures and wave data.

The neutral Stanton number, CHN, was found to follow predictions from surface‐renewal theory quite well for unstable conditions up to a wind speed of about 10 m s−1. For higher wind speeds the experimental data deviate to an increasing extent from the prediction based on surface‐renewal theory, giving 20–40% higher values at 14 m s−1. The CHN value at 14 m s−1 and unstable stratification is about 1.5×10−3; the corresponding value at the same wind speed but with slightly stable conditions is only 0.5×10−3. The interpretation is made that spray is the cause of the rapid increase of heat exchange with wind speed above about 10 m s−1. It also explains the drop in CHN at neutral stability, the spray‐mediated sensible‐heat flux increasing the upward directed flux of sensible heat in unstable conditions and decreasing the flux in stable conditions.

For stable conditions, CHN data are widely scattered, with a mean of about 0.75×10−3. It appears that the data have an approximate upper bound given by surface‐renewal theory. It is suggested that at least some of the strong suppression of the flux of sensible heat during stable conditions can be explained as a shear‐sheltering effect caused by the presence of a low‐level wind maximum. Copyright © 2004 Royal Meteorological Society
Variability in the summertime coastal marine atmospheric boundary‐layer off California, USA
Authors: Ström Linda , Tjernström Michael
Published: March 2004

An analysis of boundary‐layer structure and surface‐layer turbulence from measurements off the California coast is presented from data collected by research aircraft during two field experiments: the Coastal Waves 1996 (CW96) and the Monterey Area Ship Track (MAST) experiments. CW96 covers the near‐coast region, in particular in the vicinity of major headlands, whereas MAST extends offshore.

Along the US west coast, coastal modification of the along‐coast flow occurs on two main horizontal scales. Firstly, a large‐scale variability is due to the interplay between the shallow near‐coast marine atmospheric boundary‐layer (MABL) and the coastal terrain, typically higher than the MABL depth. The MABL depth decreases smoothly towards the coast while the wind speed increases to a coastal jet in response to the sloping MABL inversion. Secondly, the flow is affected by supercritical flow dynamics. As the wind speed increases and the MABL depth decreases towards the coast, the MABL flow becomes supercritical in a shallow‐water sense. As supercritical shallow‐water flow interacts with major headlands, expansion fans form, affecting both the wind speed and the MABL depth.

The combination of CW96 and MAST data reveals significant differences between the flow along the coast and that far offshore. MABL winds are stronger near the coast whereas aloft the winds are weaker than offshore. The near‐coast MABL is also better mixed. Turbulence increases towards the coast while the sensible‐heat flux decreases and often changes sign, leading to stable stratification near the coast. A length‐scale determining the across‐coast influence of the expansion fans is defined from simple inviscid and irrotational shallow‐water theory. Data from four days of the CW96 experiment show that this simple theory describes the low‐level wind speed adequately. Surface‐layer turbulence also scales with this simple length‐scale, but the results are complicated by upwelling of cold water, giving rise to strong internal boundary‐layers. From terms in the turbulent‐energy budgets it appears that dissipation of turbulence exceeds local production. Copyright © 2004 Royal Meteorological Society
A study of departures from the inverse‐barometer response of sea level to air‐pressure forcing at a period of 5 days
Authors: Mathers E. L. , Woodworth P. L.
Published: March 2004

The response of the sea level to atmospheric forcing is investigated through the cross‐spectral analysis of tide‐gauge data from around 100 island and deep‐ocean stations and atmospheric pressure records. The focus is at a period of 5 days, coinciding with an atmospheric pressure oscillation (Madden–Julian wave) of the same frequency. Outside the Tropics the energy in synoptic weather systems masks the small amplitude of the pressure wave, resulting in a response indistinguishable from that of an inverse barometer (IB). Within the Tropics, variability of air pressure is smaller in comparison with the amplitude of the pressure wave and departures from the IB model are found. Analysis of several sub‐surface pressure records in the tropical Atlantic also yields departures at this time‐scale, and indicates the barotropic nature of the response. Findings from a near‐global barotropic numerical model forced with realistic air pressure and wind‐stress fields show reasonable agreement with results at tide‐gauge locations, and provide a more complete view of the sea‐level response. These results indicate the possibility of providing an improved simulation of sea‐level response to atmospheric‐pressure forcing at this time‐scale than is currently provided by the IB model, for example in the field of satellite altimetry. Copyright © 2004 Royal Meteorological Society
Dynamics of the surface wind field over the equatorial Indian Ocean
Authors: Hastenrath Stefan , Polzin Dierk
Published: March 2004

The annual cycle and interannual variability of the equatorial westerlies over the Indian Ocean are examined in the context of the equations of motion, using long‐term surface ship observations. Eastward pressure gradient along the equator may accelerate equatorial westerlies, but the process is more intricate. The south Indian Ocean trade winds can recurve in the southern hemisphere only with an eastward pressure gradient. This is counteracted by the Coriolis acceleration directed at right angles to the left of the motion. With weak trades and strong eastward pressure gradient, the flow can recurve at relatively high southern latitudes, thus allowing a broad equatorial zone in which westerlies can develop. In the annual cycle, the southern Indian Ocean high and trade winds are closest to the equator and strongest in austral winter when, however, the eastward pressure gradient in the equatorial zone is also steepest. Accordingly, the latitude of flow recurvature in the southern trade winds stays farthest away from the equator in boreal spring and autumn. Consequently, the equatorial westerlies peak in these short transition seasons. The boreal autumn equatorial westerlies are the surface manifestation of a powerful zonal circulation cell along the Indian Ocean equator. The interannual variability of boreal autumn is characterized by weak westerlies accompanying a slack zonal pressure gradient and strong southern trade winds with recurvature near the equator. Such an ensemble of circulation departures is characteristic of abundant rainfall in East Africa and deficient precipitation in Indonesia. Copyright © 2004 Royal Meteorological Society
Class Scheduling for Pilot Training
Authors: Qi Xiangtong , Bard Jonathan F. , Yu Gang
Published: March 2004

In this paper, we study the class scheduling problem at the training center of Continental Airlines. When pilots get new assignments, they must be retrained for up to eight consecutive weeks. During that time, they are removed from the roster, and thus impose a significant cost on the airlines. We formulate the problem with the objective of minimizing the total weighted length of all classes. Solutions are obtained with a branch-and-bound algorithm and a family of heuristics based on the idea of a rolling horizon. A series of computational experiments is performed to evaluate the algorithms. The results indicate that it is possible to obtain near-optimal solutions within acceptable time limits. The algorithms have been implemented and are now in use at Continental.
On the Dialectics of Strategic Alliances
Authors: de Rond Mark , Bouchikhi Hamid
Published: March 2004

Using Van de Ven and Poole's (1995) extensive assessment of process theories as an intellectual scaffold, we review theoretical contributions to our understanding of alliance dynamics and process. It appears that of four generic theoretical engines, only three—life cycle, teleology, and evolution—are reasonably well covered in this literature. Process studies informed by a dialectical theory, however, appear to be markedly absent. We explore the characteristics and contributions of a dialectical lens in understanding interorganizational collaborations by invoking a longitudinal case study of a biotechnology-based alliance. The case illustrates the coevolutionary interchange of design and emergence, cooperation and competition, trust and vigilance, expansion and contraction, and control and autonomy. It also emphasizes the importance of treating alliances as heterogeneous phenomena, of alliance performance as subject to social construction, and of unintended consequences as a change agent. The emerging ontological, epistemological, and methodological implications of a dialectical perspective comprise a novel extension to the existing literature.
Knowledge Networks as Channels and Conduits: The Effects of Spillovers in the Boston Biotechnology Community
Authors: Owen-Smith Jason , Powell Walter W.
Published: March 2004

We contend that two important, nonrelational, features of formal interorganizational networks—geographic propinquity and organizational form—fundamentally alter the flow of information through a network. Within regional economies, contractual linkages among physically proximate organizations represent relatively transparent channels for information transfer because they are embedded in an ecology rich in informal and labor market transmission mechanisms. Similarly, we argue that the spillovers that result from proprietary alliances are a function of the institutional commitments and practices of members of the network. When the dominant nodes in an innovation network are committed to open regimes of information disclosure, the entire structure is characterized by less tightly monitored ties. The relative accessibility of knowledge transferred through contractual linkages to organizations determines whether innovation benefits accrue broadly to membership in a coherent network component or narrowly to centrality. We draw on novel network visualization methods and conditional fixed effects negative binomial regressions to test these arguments for human therapeutic biotechnology firms located in the Boston metropolitan area.
Intra-Amygdala Administration of Polyamines Modulates Fear Conditioning in Rats
Authors: Rubin Maribel A. , Berlese Daiane B. , Stiegemeier Juliano A. , Volkweis Márcio A. , Oliveira Denise M. , dos Santos Telma L. B. , Fenili Ana C. , Mello Carlos F.
Published: March 2004

Amygdalar NMDA receptor activation has been implicated in the acquisition of fear memories in rats. However, little is known about the role of endogenous modulators of the NMDA receptor, such as polyamines, in pavlovian fear-conditioning learning. Therefore, in the present study we investigated whether the immediate pretraining or post-training bilateral infusion of arcaine, an antagonist of the NMDA receptor polyamine-binding site, or spermidine, an agonist of the NMDA receptor polyamine-binding site, into the amygdala affected classical fear conditioning in rats. Bilateral microinjections of arcaine (0.0002-0.2 nmol) decreased, whereas spermidine (0.002-20 nmol) increased, contextual and auditory fear conditioning. Arcaine coadministration, at a dose that had no effect per se, reversed the facilitatory effect of spermidine. These results provide evidence that endogenous and exogenous polyamines modulate the acquisition or early consolidation (or both) of the fear-conditioning task in the amygdala.
Environmental Enrichment Rescues Protein Deficits in a Mouse Model of Huntington's Disease, Indicating a Possible Disease Mechanism
Authors: Spires Tara L. , Grote Helen E. , Varshney Neelash K. , Cordery Patricia M. , van Dellen Anton , Blakemore Colin , Hannan Anthony J.
Published: March 2004

Huntington's disease (HD) is a devastating neurodegenerative disorder caused by a CAG repeat expansion encoding an extended polyglutamine tract in the huntingtin protein. Transgenic mice expressing a humanhuntingtintransgene containing an expanded CAG repeat (R6/1 model) develop a neurodegenerative disorder closely resembling human HD. Previous work demonstrated that environmental enrichment delays the onset of motor symptoms in this mouse model. We confirmed that at 5 months of age, enrichment ameliorates motor symptoms (assessed using the rotarod test) and prevents loss of body weight induced by the HD transgene. We further examined molecular consequences of enrichment by determining changes in protein levels in the neostriatum, hippocampus, and anterior cortex using quantitative Western blot analysis. Non-enriched HD mice have severe reductions in BDNF in the hippocampus and striatum at 5 months, which are entirely rescued by enrichment. BDNF levels are unaltered by HD in the anterior cortex, suggesting that enrichment might prevent HD-induced impairment of anterograde transport of this neurotrophin to the striatum. NGF is unaffected by HD. Non-enriched HD mice also exhibit deficits in dopamine and cAMP-regulated phosphoprotein (32 kDa) in striatum and anterior cortex. Environmental enrichment rescues the cortical but not the striatal deficit at 5 months. These results suggest that environmental enrichment benefits animals at early stages of the disease by rescuing protein deficits, possibly through rescuing transcription or protein transport problems.
Why Is Spatial Stereoresolution So Low?
Authors: Banks Martin S. , Gepshtein Sergei , Landy Michael S.
Published: March 2004

Spatial stereoresolution (the finest detectable modulation of binocular disparity) is much poorer than luminance resolution (finest detectable luminance variation). In a series of psychophysical experiments, we examined four factors that could cause low stereoresolution: (1) the sampling properties of the stimulus, (2) the disparity gradient limit, (3) low-pass spatial filtering by mechanisms early in the visual process, and (4) the method by which binocular matches are computed. Our experimental results reveal the contributions of the first three factors. A theoretical analysis of binocular matching by interocular correlation reveals the contribution of the fourth: the highest attainable stereoresolution may be limited by (1) the smallest useful correlation window in the visual system, and (2) a matching process that estimates the disparity of image patches and assumes that disparity is constant across the patch. Both properties are observed in disparity-selective neurons in area V1 of the primate (Nienborg et al., 2004).
Receptive Field Size in V1 Neurons Limits Acuity for Perceiving Disparity Modulation
Authors: Nienborg Hendrikje , Bridge Holly , Parker Andrew J. , Cumming Bruce G.
Published: March 2004

Disparity selectivity in the striate cortex has generally been studied with uniform disparity fields covering the receptive field (RF). In four awake behaving monkeys, we quantitatively characterized the spatial three-dimensional structure of 55 V1 RFs using random dot stereograms in which disparity varied as a sinusoidal function of vertical position (“corrugations”). At low spatial frequencies, this produced a modulation in neuronal firing at the temporal frequency of the stimulus. As the spatial frequency increased, the modulation reduced. The mean response rate changed little and was close to that produced by a uniform stimulus at the mean disparity of the corrugation. In 48 of 55 (91%) neurons, the modulation strength was a lowpass function of spatial frequency. These results are compatible with a response determined only by the weighted mean of the disparities of the dots (the weights being set by the RF envelope) and suggest that there is no disparity-based surround inhibition or selectivity for disparity gradients. This simple weighting scheme predicts a relationship between RF size and the high-frequency cutoff. Comparison with independent measurements of RF size was compatible with this. All of this behavior closely matches the binocular energy model. The mean cutoff frequency, 0.5 cycles per degree, is similar to equivalent measures of decline in human psychophysical sensitivity for such depth corrugations as a function of frequency (Tyler, 1974; Prince and Rogers, 1998; Banks et al., 2004). This suggests that human cyclopean acuity for disparity modulations is limited by the selectivity of V1 neurons. This in turn is primarily limited by the RF size, because we find no sensitivity for disparity gradients or other disparity differences within the RFs.
Dissociating Self-Generated from Passively Applied Head Motion: Neural Mechanisms in the Vestibular Nuclei
Authors: Roy Jefferson E. , Cullen Kathleen E.
Published: March 2004

The ability to distinguish sensory inputs that are a consequence of our own actions from those that result from changes in the external world is essential for perceptual stability and accurate motor control. To accomplish this, it has been proposed that an internal prediction of the consequences of our actions is compared with the actual sensory input to cancel the resultant self-generated activation. Here, we provide evidence for this hypothesis at an early stage of processing in the vestibular system. Previous studies have shown that neurons in the vestibular nucleus, which receive direct inputs from vestibular afferent fibers, are responsive to passively applied head movements. However, these same neurons do not reliably encode head velocity resulting from self-generated movements of the head on the body. In this study, we examined the mechanism that underlies the selective elimination of vestibular sensitivity to active head-on-body rotations. Individual neurons were recorded in monkeys making active head movements. The correspondence between intended and actual head movement was experimentally controlled. We found that a cancellation signal was gated into the vestibular nuclei only in conditions in which the activation of neck proprioceptors matched that expected on the basis of the neck motor command. This finding suggests that vestibular signals that arise from self-generated head movements are inhibited by a mechanism that compares the internal prediction of the sensory consequences by the brain to the actual resultant sensory feedback. Because self-generated vestibular inputs are selectively cancelled early in processing, we propose that this gating is important for the computation of spatial orientation and control of posture by higher-order structures.
Allelic Variation of theTas1r3Taste Receptor Gene Selectively Affects Behavioral and Neural Taste Responses to Sweeteners in the F2Hybrids between C57BL/6ByJ and 129P3/J Mice
Authors: Inoue Masashi , Reed Danielle R. , Li Xia , Tordoff Michael G. , Beauchamp Gary K. , Bachmanov Alexander A.
Published: March 2004

Recent studies have shown that the T1R3 receptor protein encoded by theTas1r3gene is involved in transduction of sweet taste. To assess ligand specificity of the T1R3 receptor, we analyzed the association ofTas1r3allelic variants with taste responses in mice. In the F2hybrids between the C57BL/6ByJ (B6) and 129P3/J (129) inbred mouse strains, we determined genotypes of markers on chromosome 4, whereTas1r3resides, measured consumption of taste solutions presented in two-bottle preference tests, and recorded integrated responses of the chorda tympani gustatory nerve to lingual application of taste stimuli. For intakes and preferences, significant linkages toTas1r3were found for the sweeteners sucrose, saccharin, andd-phenylalanine but not glycine. For chorda tympani responses, significant linkages toTas1r3were found for the sweeteners sucrose, saccharin,d-phenylalanine,d-tryptophan, and SC-45647 but not glycine,l-proline,l-alanine, orl-glutamine. No linkages to distal chromosome 4 were detected for behavioral or neural responses to non-sweet quinine, citric acid, HCl, NaCl, KCl, monosodium glutamate, inosine 5′-monophosphate, or ammonium glutamate. These results demonstrate that allelic variation of theTas1r3gene affects gustatory neural and behavioral responses to some, but not all, sweeteners. This study describes the range of ligand sensitivity of the T1R3 receptor using anin vivoapproach and, to our knowledge, is the first genetic mapping study of activity in gustatory nerves.
Corticospinal System Development Depends on Motor Experience
Authors: Martin John H. , Choy Michelle , Pullman Seth , Meng Zhuo
Published: March 2004

Early motor experiences have been shown to be important for the development of motor skills in humans and animals. However, little is known about the role of motor experience in motor system development. In this study, we address the question of whether early motor experience is important in shaping the development of the corticospinal (CS) tract. We prevented limb use by the intramuscular injection of botulinum toxin A into selected forelimb muscles to produce muscle paralysis during the period of development of CS connection specificity, which is between postnatal weeks 3 and 7. CS terminations were examined using an anterograde tracer. Preventing normal forelimb use during CS axon development produced defective development of CS terminations at week 8 and in maturity. There were reductions in the topographic distribution of axon terminals, in terminal and preterminal branching, and in varicosity density. This suggests that limb use is needed to refine CS terminals into topographically specific clusters of dense terminal branches and varicosities. To determine correlated effects on motor behavior, cats were tested in a prehension task, to reach and grasp a piece of food from a narrow food well, when the neuromuscular blockade dissipated (by week 10) and in maturity (week 16). Preventing normal limb use also produced a prehension deficit later in development and in maturity, in which there was a loss of the supination component of grasping. This component of prehension in the cat depends on CS projections from the paw representation of rostral motor cortex to the cervical enlargement. Our findings show that motor experiences are necessary for normal development of CS terminations and function.
Generation of Reelin-Positive Marginal Zone Cells from the Caudomedial Wall of Telencephalic Vesicles
Authors: Takiguchi-Hayashi Keiko , Sekiguchi Mariko , Ashigaki Shizuko , Takamatsu Masako , Hasegawa Hiroshi , Suzuki-Migishima Rika , Yokoyama Minesuke , Nakanishi Shigetada , Tanabe Yasuto
Published: March 2004

An early and fundamental step of the laminar organization of developing neocortex is controlled by the developmental programs that critically depend on the activities of reelin-positive cells in the marginal zone. However, the ontogeny of reelin-positive cells remained elusive. To gain insights into the spatial and temporal regulation of reelin-positive marginal zone cell development, we used a transgenic mouse line in which we defined the green fluorescent protein (GFP) transgene as a novel reliable molecular marker of reelin-positive marginal zone cells from the early stages of their development. We further usedexo uteroelectroporation-mediated gene transfer that allows us to mark progenitor cells and monitor the descendants in the telencephalonin vivo. We show here the generation of reelin-positive marginal zone cells from the caudomedial wall of telencephalic vesicles, including the cortical hem, where the prominent expression of GFP is initially detected. These neurons tangentially migrate at the cortical marginal zone and are distributed throughout the entire neocortex in a caudomedial-high to rostrolateral-low gradient during the dynamic developmental period of corticogenesis. Therefore, our findings on reelin-positive marginal zone cells, in addition to the cortical interneurons, add to the emerging view that the neocortex consists of neuronal subtypes that originate from a focal source extrinsic to the neocortex, migrate tangentially into the neocortex, and thereby underlie neural organization of the neocortex.
Propofol Restores the Function of “Hyperekplexic” Mutant Glycine Receptors inXenopusOocytes and Mice
Authors: O'Shea Sean Michael , Becker Lore , Weiher Hans , Betz Heinrich , Laube Bodo
Published: March 2004

Human hereditary hyperekplexia (“startle disease”) is a neurological disorder characterized by exaggerated, convulsive movements in response to unexpected stimuli. Molecular genetic studies have shown that this disease is often caused by amino acid substitutions at arginine 271 to glutamine or leucine of the α1subunit of the inhibitory glycine receptor (GlyR). When exogenously expressed inXenopusoocytes, agonist responses of mutant α1(R271Q) and α1(R271L) GlyRs show higher EC50values and lower maximal inducible responses (relative efficacies) compared with oocytes expressing wild-type α1GlyR subunits. Here, we report that the maximal glycine-induced currents (Imax) of mutant α1(R271Q) and α1(R271L) GlyRs were dramatically potentiated in the presence of the anesthetic propofol (PRO), whereas theImaxof wild-type α1receptors was not affected. Quantitative analysis of the agonist responses of the isofunctionally substituted α1(R271K) mutant GlyR revealed that saturating concentrations of PRO decreased the EC50values of both glycine and the partial agonist β-alanine by >10-fold, with relative efficacies increasing by 4- and 16-fold, respectively. Transgenic (tg) mice carrying the α1(R271Q) mutation (tg271Q-300) have both spontaneous and induced tremor episodes that closely resemble the movements of startled hyperekplexic patients. After treatment with subanesthetic doses of PRO, the tg271Q-300 mutant mice showed temporary reflexive and locomotor improvements that made them indistinguishable from wild-type mice. Together, these results demonstrate that the functional and behavioral effects of hyperekplexia mutations can be effectively reversed by drugs that potentiate GlyR responses.
Role of Tumor Necrosis Factor-α in Methamphetamine-Induced Drug Dependence and Neurotoxicity
Authors: Nakajima Akira , Yamada Kiyofumi , Nagai Taku , Uchiyama Takehisa , Miyamoto Yoshiaki , Mamiya Takayoshi , He Jue , Nitta Atsumi , Mizuno Makoto , Tran Manh Hung , Seto Aika , Yoshimura Masako , Kitaichi Kiyoyuki , Hasegawa Takaaki , Saito Kuniaki , Yamada Yasuhiro , Seishima Mitsuru , Sekikawa Kenji , Kim Hyoung-Chun , Nabeshima Toshitaka
Published: March 2004

Tumor necrosis factor-α (TNF-α), a proinflammatory cytokine, is now emerging as an important modulator of the function of the CNS. Methamphetamine (METH) is a widely abused psychostimulant that causes euphoria, hyperactivity, and drug dependence. High doses of METH cause long-term neurotoxicity in dopaminergic neurons. In this study, we investigated a role of TNF-α in METH-induced dependence and neurotoxicity. Repeated treatment with METH (2 mg/kg for 5 d) in rats induced a significant increase in TNF-α mRNA and protein expression in the brain. Exogenous TNF-α (1-4 μg) blocked locomotor-stimulating and rewarding effects of METH, as well as METH (4 mg/kg; four times at 2 hr intervals)-induced dopaminergic neurotoxicity in mice. To examine a role of endogenous TNF-α in behavioral and neurochemical effects of METH, we used mice with targeted deletions of the TNF-α gene. TNF-α-(-/-) mice showed enhanced responses to the locomotor-sensitizing, rewarding, and neurotoxic effects of METH compared with wild-type mice. We also examined the role of TNF-α in METH-induced dopamine (DA) release and uptakein vitroandin vivoin C57BL/6 mice. Exogenous TNF-α (4 μg) attenuated the METH-induced increase in extracellular striatal DAin vivoand potentiated striatal DA uptake into synaptosomesin vitroandin vivo. Furthermore, TNF-α activated vesicular DA uptake by itself and diminished the METH-induced decrease in vesicular DA uptake. Our findings suggest that TNF-α plays a neuroprotective role in METH-induced drug dependence and neurotoxicity by activating plasmalemmal and vesicular DA transporter as well as inhibiting METH-induced increase in extracellular DA levels.