bluuebunny/crossref_metadata_2025 huggingface dataset:
Validation of Multimedia Models Assessing Exposure to PAHs—The SOLEX Study
Authors: Dor Frédéric , Empereur‐Bissonnet Pascal , Zmirou Denis , Nedellec Vincent , Haguenoer Jean‐Marie , Jongeneelen Frans , Person Alain , Dab William , Ferguson Colin
Published: September 2003

Polluted soils have become a public health problem. While population exposure to soil pollutants is generally quantified using multimedia models, their estimations have not been validated, and studies that attempted to do so are scarce. The objective of the SOLEX study was to compare the predictions of pyrene exposure levels (converted into 1 hydroxypyrene) computed by several models with the results of urinary 1‐hydropyrene (1‐HOP) assays among 110 employees working at three sites polluted during their past use as manufactured gas plants. Four models were used: AERIS (Canada), CalTOX (California, USA), CLEA (UK), and HESP (The Netherlands). Three occupational exposure scenarios—with office, mixed, and outdoor workers—were constructed, based upon job activities during two measurement campaigns, one in winter and one in summer. The exposure levels estimated by the four models could differ markedly (from 7 up to 80 times) according to the exposure scenario. Also, the predominant exposure routes differed according to the model (direct soil ingestion for HESP and CalTOX, inhalation for AERIS, and dermal absorption for CLEA). The predictions of CalTOX are consistent with the 1‐HOP measurements for all the scenarios. For HESP, the consistency is observed for the scenarios, office and mixed, for which the pyrene level in the soil is low. AERIS and CLEA yield results that are systematically above the 1‐HOP measurements. This study confirms that validation of the models is crucial and points out to the need to proceed to assess components of the models that are the most influential using appropriate statistical analysis in combination with true field data.
A Framework and Case Study for Exposure Assessment in the Voluntary Children's Chemical Evaluation Program
Authors: Reiss Richard , Anderson Elizabeth L. , Lape James
Published: September 2003

A conceptual framework is presented for conducting exposure assessments under the U.S. EPA's Voluntary Children's Chemical Evaluation Program (VCCEP). The VCCEP is a voluntary program whereby companies that manufacture chemicals of potential concern are asked to conduct hazard, exposure, and risk assessments for the chemicals. The VCCEP is unique in its risk‐based, tiered approach, and because it focuses on children and requires a comprehensive consideration of all reasonably foreseeable exposure pathways for a particular chemical. The consideration of all potential exposure pathways for some commonly used chemicals presents a daunting challenge for the exposure assessor. This article presents a framework for managing this complicated process, and illustrates the application of the framework with a hypothetical case study. The framework provides guidance for interpreting multiple sources of exposure information and developing a plausible list of exposure pathways for a chemical. Furthermore, the framework provides a means to process all the available information to eliminate pathways of negligible concern from consideration. Finally, the framework provides guidance for utilizing the tiered approach of VCCEP to efficiently conduct an assessment by first using simple, screening‐level approaches and then, if necessary, using more complex, refined exposure assessment methods. The case study provides an illustration of the major concepts.
National Security versus Civil Liberties
Authors: Baker Nancy V.
Published: September 2003

Political, media, and academic observers have consistently noted the adverse impact of post‐9/11 antiterrorism measures on civil liberties, yet Attorney General John Ashcroft and others in the administration insist that the measures are consistent with constitutional values. The national security versus civil liberties debate has special saliency during wartime, particularly an open‐ended war against terrorism. Responding to the attacks as a war—instead of a crime against humanity—has led to two domestic developments for the presidency: first, the centralization of authority in the White House, and second, the securitization of the domestic sphere, specifically the administration's view of civil liberties as a weakness in the system that can be exploited by terrorists. This study focuses on the second of these developments. It examines how the conception of liberties as points of vulnerability compels the administration to restrict individual rights while, at the same time, to deny that it is doing so.
The role of trapped Ar atoms in the mechanical properties of boron carbide films deposited by dc-magnetron sputtering
Authors: Jacobsohn L. G. , Averitt R. D. , Nastasi M.
Published: September 2003

Boron carbide films were deposited by dc-magnetron sputtering and their composition, chemical bonding and mechanical properties were investigated as a function of the substrate bias voltage. The films are stoichiometric within the entire range of substrate bias voltages employed as determined by Rutherford backscattering spectrometry. As the substrate bias voltage increases, higher amounts of trapped Ar atoms are found in the films. A decrease of the number of B–C bonds is observed while the hardness decreases and the compressive stress increases. It is suggested that the trapped Ar atoms are in substitutional sites and act to inhibit chemical bonds within the amorphous network which leads to softer films. The trapped Ar atoms also induce local expansion of the amorphous network and a correlation between the amount of trapped Ar atoms and the magnitude of the compressive internal stress is suggested.
Reaction between nitrogen gas and silicon species during pulsed laser ablation
Authors: Umezu Ikurou , Inada Mitsuru , Kohno Kimihiro , Yamaguchi Tomohiro , Makino Toshiharu , Sugimura Akira
Published: September 2003

The reaction processes occurring during the formation of silicon nitride films were investigated in this study. Films were deposited by pulsed laser ablation (PLA) of a silicon target in nitrogen gas. To reveal reaction processes during the film deposition, both the nitrogen gas pressure and the applied laser fluence were varied. The size of the plume fluorescence and the properties of the resulting film were measured as functions of gas pressure and laser fluence. It was found that the reaction between nitrogen gas and silicon clusters in the plume region effectively takes place under limited conditions. The decomposition of the background gas and multiple collisions of the silicon species in the plume region are essential for the reactive PLA method. Confinement of the species in the plume is one of the key factors to determine the composition and morphology of the film.
Major advances in transfer pumps: 1953–2003
Authors: Hablanian M. H.
Published: September 2003

The major advances made in the design and operation of transfer pumps (i.e., vacuum pumps that transfer gas from a vacuum system to the atmosphere) during the lifetime of the American Vacuum Society (1953–2003) are reviewed. Included are diffusion, turbomolecular, and oil-free mechanical pumps.
Fifty years of vacuum science
Authors: Hobson J. P.
Published: September 2003

A selection is presented of problems in the physics and chemistry of vacuum systems and devices which has attracted considerable research during the past 50 years. These include examples where the limiting gas sources are water vapor, hydrogen, or helium. Also considered are self-sustained crossed-field discharges and the interaction of molecules, electrons, ions, and photons with the “technical” surfaces found in most vacuum systems.
Plasma–surface interactions
Authors: Chang J. P. , Coburn J. W.
Published: September 2003

Over the past decades, our understanding of the fundamental processes occurring in the plasma and at plasma–material interfaces has evolved from being macroscopic and phenomenological to microscopic and mechanistic. This article aims to provide an overview of the evolution of our understanding of several interesting and important phenomena associated with plasma–surface interactions and suggest some future applications of plasma.
Damage effects from medium-energy ion bombardment during the growth of cubic-boron nitride films
Authors: Gago R. , Vinnichenko M. , Abendroth B. , Kolitsch A. , Möller W.
Published: September 2003

Cubic-boron nitride (c-BN) films with low stress have been produced by simultaneous 35 keV N+ ion implantation during growth by ion assisted sputtering. The stress release is achieved at the lost of a decrease in the c-BN content. Despite this fact, films with a high c-BN content and relatively large thickness (∼0.4 μm) have been produced. The decrease on the c-BN content is discussed in terms of the damage induced by the medium-energy ion implantation.
Evidences for dry deintercalation in layered compounds upon controlled surface charging in x-ray photoelectron spectroscopy
Authors: Feldman Y. , Zak A. , Tenne R. , Cohen H.
Published: September 2003

Pronounced surface diffusion is observed during x-ray photoelectron spectroscopy measurements of 2H platelets and inorganic fullerene-like (IF) MS2 (M=W,Mo) powders, intercalated with alkaline (A=K,Na) elements. Using controlled surface charging the intercalants migrate towards the surface, where they oxidize. This dry deintercalation is controllable via external charging parameters, yet showing that internal chemical and structural parameters play an important role in the process. Diffusion rates out of 2H matrixes are generally higher than in corresponding IF samples. Clear differences are also found between Mo and W-based systems. Application of this approach into surface modification and processing is proposed.
Experimental consequences of time variations of the fundamental constants
Authors: Rich J.
Published: September 2003

We discuss the experimental consequences of hypothetical time variations of the fundamental constants. We show that any observed time variations can be interpreted as being due to changes in the dimensionless fundamental constants, once the effects of the constants on the structure of the experiment are taken into account. Young’s experiment for a slow charged particle and a version of the twin paradox are discussed to show how their results are independent of physical constants. We also show that experiments that are generally interpreted in terms of time variations of the gravitational constant G are better interpreted as giving limits on the variation of the dimensionless constant αG=Gmp2/ℏc, where mp is the mass of the proton.
Landau theory of domain walls for one-dimensional asymmetric potentials
Authors: Sanati Mahdi , Saxena Avadh
Published: September 2003

Investigation of a great number of physical systems shows that a Landau free energy of the form F(φ)=Hφ+(A/2)φ2+(B/3)φ3+(C/4)φ4 describes a first-order phase transition in an internal or external field H. To study the formation of static domain walls in these systems we include a spatial gradient (Ginzburg) term of the scalar order parameter φ. From the variational derivative of the total free energy we obtain a static equilibrium condition. By solving this equation exactly for different physical parameters and boundary conditions, we obtained different quasi-one-dimensional soliton-like solutions. These solutions correspond to three different types of domain walls between the two different phases which are created in the system. In addition, we obtain soliton lattice (domain wall array) solutions, calculate their formation energy and the asymptotic interaction between the solitons. By introducing certain transformations, we show that the solutions obtained here can be used to study domain walls in other physical systems such as described by asymmetric double Morse potentials. Finally, we apply our results to the specific cases of liquid crystals and the jam phenomena in traffic flows.
Casimir forces and boundary conditions in one dimension: Attraction, repulsion, Planck spectrum, and entropy
Authors: Boyer Timothy H.
Published: September 2003

Quantities associated with Casimir forces are calculated in a model wave system of one spatial dimension where the physical ideas are transparent and the calculations allow easy numerical evaluation. The calculations show strong dependence upon fixed- or free-end (Dirichlet or Neumann) boundary conditions for waves on a one-dimensional string, analogous to infinitely-conducting or infinitely-permeable materials for electromagnetic waves. (1) Due to zero-point fluctuations, a partition in a one-dimensional box is found to be attracted to the walls if the wave boundary conditions are alike for the partition and the walls, but is repelled if the conditions are different. (2) The use of Casimir energies in the presence of zero-point radiation introduces a natural maximum-entropy principle which is satisfied only by the Planck spectrum for both like and unlike boundary conditions between the walls and partition. (3) The one-dimensional Casimir forces are attractive and increasing with temperature for like boundary conditions, but are repulsive and decreasing with temperature for unlike boundary conditions. (4) In the high-temperature limit, there is a temperature-independent Casimir entropy for like boundary conditions, but a vanishing Casimir entropy for unlike boundary conditions. These one-dimensional results have counterparts for electromagnetic Casimir forces in three dimensions.
A temperature relaxation method for the measurement of the specific heat of solids at room temperature in student laboratories
Authors: Marı́n E. , Delgado-Vasallo O. , Valiente H.
Published: September 2003

A laboratory experiment is described which employs a relaxation method for the measurement of the specific heat at constant pressure of solids at room temperature. The experiment employs measurements of the cooling (or heating) rate of a sample whose temperature differs from that of the surroundings due to light heating. This rate depends on the temperature difference, the specific heat of the sample and the heat transfer coefficient. The sample is suspended adiabatically in a reservoir in which a vacuum can be made. The influence of heat dissipation by convection on the results is discussed for the first time for this kind of experiment. The theoretical aspects related to the described technique involve concepts from several branches of physics that makes the experiment of interest and suitable for students at undergraduate and graduate levels of physics, material sciences and engineering.
Metapopulation Persistence with Age-Dependent Disturbance or Succession
Authors: Hastings Alan
Published: September 2003

Simple metapopulation models with random disturbances are used in species conservation or management, relying on the condition for persistence that the per-patch colonization rate be greater than the per-patch extinction rate. For a general model incorporating the role of succession or patch age–dependent extinction, I show that persistence requires the per-patch colonization rate to be greater than the inverse of mean patch age, where age is the time since the patch became available for colonization. Because mean patch age can be arbitrarily large relative to the extinction rate, currently persisting metapopulations may be persisting despite small colonization rates, and management approaches that do not consider the role of mean patch age may unnecessarily doom populations to extinction.
Electronic Structure Control of Single-Walled Carbon Nanotube Functionalization
Authors: Strano Michael S. , Dyke Christopher A. , Usrey Monica L. , Barone Paul W. , Allen Mathew J. , Shan Hongwei , Kittrell Carter , Hauge Robert H. , Tour James M. , Smalley Richard E.
Published: September 2003

Diazonium reagents functionalize single-walled carbon nanotubes suspended in aqueous solution with high selectivity and enable manipulation according to electronic structure. For example, metallic species are shown to react to the near exclusion of semiconducting nanotubes under controlled conditions. Selectivity is dictated by the availability of electrons near the Fermi level to stabilize a charge-transfer transition state preceding bond formation. The chemistry can be reversed by using a thermal treatment that restores the pristine electronic structure of the nanotube.
Kinematic Evidence for an Old Stellar Halo in the Large Magellanic Cloud
Authors: Minniti Dante , Borissova Jura , Rejkuba Marina , Alves David R. , Cook Kem H. , Freeman Kenneth C.
Published: September 2003

The oldest and most metal-poor Milky Way stars form a kinematically hot halo, which motivates the two major formation scenarios for our galaxy: extended hierarchical accretion and rapid collapse. RR Lyrae stars are excellent tracers of old and metal-poor populations. We measured the kinematics of 43 RR Lyrae stars in the inner regions of the nearby Large Magellanic Cloud (LMC) galaxy. The velocity dispersion equals 53 ± 10 kilometers per second, which indicates that a kinematically hot metal-poor old halo also exists in the LMC. This result suggests that our galaxy and smaller late-type galaxies such as the LMC have similar early formation histories.
Macroscopically chiral system of three independent orientational effects as a condition for absolute asymmetric synthesis
Authors: Bielski Roman , Tencer Michal
Published: September 2003

The paper introduces the concept of using three independent, macroscopic factors affecting mutual orientation of the reactant molecules to accomplish absolute asymmetric synthesis. Unlike with other methodologies of asymmetric synthesis in physical fields, none of the utilized factors is chiral in itself (as, e.g., circularly polarized light would be), but the combination of the three constitutes a macroscopically chiral influence. Examples of applicable directional factors are time-even vector fields (e.g., electric field and the directional effects of surfaces and interfaces) and the time-odd directional transport with encounter control. The directional factors employed may act simultaneously or, if their effect can be preserved, consecutively, thus allowing, e.g., a repeat use of the electric field. The electric field strength needed to achieve a practically useful degree of molecular orientation was estimated to be ca. 3 MV/cm, which is now commonly achieved with organic materials in the area of nonlinear optics. Practical implications are discussed, as well as the implications for the origins of natural homochirality.Key words: macroscopic chirality, absolute asymmetric synthesis, homochirality, physical fields.
Influence of Helicobacter pylori Infection and Omeprazole Treatment on Gastric Regional CO2
Authors: Leodolter Andreas , Glasbrenner Bernhard , Wiedeck Heide , Eberhardt Holger , Malfertheiner Peter , Brinkmann Alexander
Published: September 2003

Background: Gastric regional CO2 accumulation indicates gastric mucosal hypoperfusion in critically ill patients. CO2 is also a reaction product of urea degradation, and we therefore tested the hypothesis if regional pCO2 is influenced by Helicobacter pylori infection. Material: Seven H. pylori-positive and 7 H. pylori-negative volunteers (age range 21–30 years) were investigated. During a 6- to 7-hour observation period, we obtained every 30 min arterial blood gases, gastric juice pH from a glass pH electrode and regional pCO2 from a gastric tonometer. The study protocol included subsequent periods of baseline measurements, pentagastrin stimulation (0.6 µg/kg/h/i.v.) and application of omeprazole (40 mg i.v.). Results: Gastric regional pCO2 was increased in H. pylori-positive versus H. pylori-negative subjects before (64.4 ± 3.1 vs. 50.0 ± 2.9 mm Hg, p < 0.005) but not after application of omeprazole. The effect of omeprazole on gastric juice pH was increased in H. pylori-positive subjects (mean pH during 4 h 6.1 ± 0.3 in H. pylori-positive vs. 2.5 ± 0.2 in H. pylori-negative subjects; p < 0.0001). There was a difference in arterial pCO2 between H. pylori-positive and H. pylori- negative subjects (43.1 ± 0.3 versus 38.9 ± 0.3 mm Hg; p < 0.0001). Conclusion:H. pylori infection has a significant effect on gastric regional CO2 that is suppressed by application of a proton pump inhibitor.
Enhanced Resistance of Gastric Mucosa to Damaging Agents in the Rat Stomach Adapted to Helicobacter pylori Lipopolysaccharide
Authors: Brzozowski Tomasz , Konturek Peter C. , Moran Anthony P. , Kwiecien Slawomir , Pajdo Robert , Konturek Stanislaw J. , Drozdowicz Danuta , Ptak Agata , Pawlik Wieslaw , Hahn Eckhart G.
Published: September 2003

Background and Aim: Lipopolysaccharide (LPS) has been proposed to act as one of numerous virulence factors in the Helicobacter pylori (HP)-infected stomach. However, little is known as to whether the gastric mucosa can withstand the repeated LPS insult, and how the possible adaptation to this endotoxin influences the damage induced by strong irritants. We determined the effect of a single or repeated parenteral administration of LPS obtained from HP on acute gastric lesions induced by intragastric application of 100% ethanol (1.5 ml) and by water immersion and restraint stress (WRS). Methods: The area of the gastric lesions was measured by planimetry, mucosal gastric blood flow (GBF) was determined by H2 gas clearance, and gastric luminal content was collected for the determination of luminal NO2–/NO3– levels by the Griess reaction. Biopsy samples were taken for the measurement of prostaglandin (PG) E2 by radioimmunoassay and mucosal expression of constitutive and inducible nitric oxide synthase (cNOS and iNOS), constitutive (COX-1) and inducible cyclooxygenase (COX-2), heat shock protein 70 (HSP 70) mRNA and protein were analyzed by RT-PCR and Western blot. Results:HP LPS (1 mg/kg i.p.) injected once or 5 times produced negligible macroscopic injury and failed to influence GBF significantly compared to the injuries recorded in vehicle-controlled rats. Single and repeated (5 times) administration of HP LPS significantly reduced ethanol- and WRS-induced lesions, these protective effects were accompanied by a rise in GBF and excessive luminal release of NO. The suppression of NOS activity by L-NAME (20 mg/kg i.p.), a nonspecific NOS inhibitor, or L- (30 mg/kg i.g.), a specific iNOS inhibitor, and of COX-2 activity by NS-398 reversed the protective and hyperemic effects of single or repeated LPS administrations against ethanol and WRS damage and the accompanying rise in NO and PGE2 production. These effects of L-NAME were significantly antagonized by the addition of L-arginine, a substrate for NO synthesis. The signals for cNOS, COX-1 and HSP 70 mRNA were detected by RT-PCR in the vehicle-treated gastric mucosa, whereas gene and protein expression of iNOS, COX-2 and HSP 70 mRNA were significantly increased only in rats treated with 1 or 5 applications of HP LPS. Conclusions: Repeated injections of HP LPS enhance gastric mucosal resistance to the mucosal damage induced by ethanol and WRS via a mechanism involving mucosal overexpression of iNOS, COX-2 and HSP 70 with subsequent excessive production of NO and PGE2.
The Global Distribution of Average Volume of Alcohol Consumption and Patterns of Drinking
Authors: Rehm Jürgen , Rehn Nina , Room Robin , Monteiro Maristela , Gmel Gerhard , Jernigan David , Frick Ulrich
Published: September 2003

Aims: To make quantitative estimates on a global basis of exposure of disease-relevant dimensions of alcohol consumption, i.e. average volume of alcohol consumption and patterns of drinking. Design: Secondary data analysis. Measurements: Level of average volume of drinking was estimated by a triangulation of data on per capita consumption and from general population surveys. Patterns of drinking were measured by an index composed of several indicators for heavy drinking occasions, an indicator of drinking with meals and an indicator of public drinking. Average volume of consumption was assessed by sex and age within each country, and patterns of drinking only by country; estimates for the global subregions were derived from the population-weighted average of the countries. For more than 90% of the world population, per capita consumption was known, and for more than 80% of the world population, survey data were available. Findings: On the country level, average volume of alcohol consumption and patterns of drinking were independent. There was marked variation between WHO subregions on both dimensions. Average volume of drinking was highest in established market economies in Western Europe and the former Socialist economies in the Eastern part of Europe and in North America, and lowest in the Eastern Mediterranean region and parts of Southeast Asia including India. Patterns were most detrimental in the former Socialist economies in the Eastern part of Europe, in Middle and South America and parts of Africa. Patterns were least detrimental in Western Europe and in developed countries in the Western Pacific region (e.g., Japan). Conclusions: Although exposure to alcohol varies considerably between regions, the overall exposure by volume is quite high and patterns are relatively detrimental. The predictions for the future are not favorable, both with respect to average volume and to patterns of drinking.
Origin of the Cortical Layer I in Rodents
Authors: Jiménez David , Rivera Rocío , López-Mascaraque Laura , De Carlos Juan A.
Published: September 2003

Using birthdating techniques, we have studied when cells that settle in the marginal zone (future layer 1) of the cortical neuroepithelium are generated in developing rat embryos. The majority of marginal zone cells are generated at embryonic day 12 (E12), E13 and E14, although some cells generated later can incorporate into this stratum after the cortical plate forms. The nature and the origin of the cell populations that colonize the preplate/marginal zone was studied by means of immunohistochemistry using cell markers for γ-amino butyric acid (GABA), reelin and the calcium binding proteins calretinin and calbindin. At early stages of development, the preplate is formed by Cajal-Retzius cells, subplate cells, subpial granular layer cells, some interneurons and some glial cells. With the arrival of the cortical plate cells, the subplate cells descend to occupy the stratum below. Layer 1 cells are of diverse origin as some of them are generated in the ventricular zone of the cortical neuroepithelium, whereas other cell populations come from extracortical regions such as the olfactory placode or the ganglionic eminences of the basal telencephalon. The predominant cell type in the marginal zone is the Cajal-Retzius cell, which expresses reelin and calretinin, and is probably generated in the cortical neuroepithelium. These cells can be readily distinguished from cells that come from the ganglionic eminences as these later populations mainly express GABA and calbindin. Finally, our results suggest that the cells of the subpial granular layer might be generated in the rostral pole of the lateral ganglionic eminences.
Regionally Specific Effects of BDNF on Oligodendrocytes
Authors: Du Yangzhou , Fischer Tanya Z. , Lee Lucille N. , Lercher Lauren D. , Dreyfus Cheryl F.
Published: September 2003

To define the effects of neurotrophins on oligodendrocytes, we monitored NGF, BDNF and NT-3 actions on basal forebrain (BF) and cortical populations. NGF, BDNF and NT-3 applied to BF oligodendrocytes elicited increases in expression of myelin basic protein (MBP) and enhanced the numbers of MBP+ cells, without affecting total cell numbers. In the cortex, however, while NGF and NT-3 influenced MBP expression, BDNF was without effect. To explore this apparent regional difference in BDNF action, we compared expression of the neurotrophin receptors trkA, trkB and trkC. While BF cells expressed all three trks, cortical cells did not express the full-length BDNF receptor, trkB. Interestingly, in no case was any receptor expressed by all oligodendrocytes, indicating that oligodendrocytes may be heterogeneous within a brain region. The data suggest that BF oligodendrocytes are influenced by BDNF to express MBP and are distinct in this ability from cortical cells.
Beyond Laminar Fate: Toward a Molecular Classification of Cortical Projection/Pyramidal Neurons
Authors: Hevner Robert F. , Daza Ray A.M. , Rubenstein John L.R. , Stunnenberg Henk , Olavarria Jaime F. , Englund Chris
Published: September 2003

Cortical projection neurons exhibit diverse morphological, physiological, and molecular phenotypes, but it is unknown how many distinct types exist. Many projection cell phenotypes are associated with laminar fate (radial position), but each layer may also contain multiple types of projection cells. We have investigated two hypotheses: (1) that different projection cell types exhibit characteristic molecular expression profiles and (2) that laminar fates are determined primarily by molecular phenotype. We found that several transcription factors were differentially expressed by projection neurons, even within the same layer: Otx1 and Er81, for example, were expressed by different neurons in layer 5. Retrograde tracing showed that Er81 was expressed in corticospinal and corticocortical neurons. In contrast, Otx1 has been detected only in corticobulbar neurons [Weimann et al., Neuron 1999;24:819–831]. Birthdating demonstrated that different molecularly defined types were produced sequentially, in overlapping waves. Cells adopted laminar fates characteristic of their molecular phenotypes, regardless of cell birthday. Molecular markers also revealed the locations of different projection cell types in the malformed cortex of reeler mice. These studies suggest that molecular profiles can be used advantageously for classifying cortical projection cells, for analyzing their neurogenesis and fate specification, and for evaluating cortical malformations.
Extrinsic and Intrinsic Factors Governing Cell Fate in Cortical Progenitor Cultures
Authors: Irvin Dwain K. , Dhaka Ajay , Hicks Carol , Weinmaster Gerry , Kornblum Harley I.
Published: September 2003

Central nervous system germinal zones contain stem cells that generate both neurons and glia. In the recent past, these cells have been isolated, maintained in a variety of culture systems and used in vitro for subsequent characterization of molecular mechanisms underlying brain development. Factors that govern cell fate choices of these neural stem cells have not been fully elucidated, but recent studies suggest that age at the time of culture is an important intrinsic mechanism. Stem cell mitogens and Notch-DSL signaling are significant extrinsic factors. In the current study, we compare neurosphere cultures propagated from animals on embryonic day 12, embryonic day 18 and the day of birth and stimulated to divide by either basic fibroblast growth factor (bFGF) or transforming growth factor-α (TGF-α). As described for other systems, when bFGF was used, clonal neurospheres derived from the youngest age gave rise to a greater percentage of neurons. When TGF-α, acting via the epidermal growth factor receptor, was used, this effect was not observed, with neurospheres from younger animals giving rise to a similar percentage of neurons as those derived from older animals suggesting that this growth factor was either stimulating a different population of stem cells to proliferate, or that it was capable of overriding intrinsic mechanisms. Other differences were also observed when the two growth factors were compared, including age-dependent differences in the numbers of putative astrocytes and oligodendrocytes formed. We further assessed age-dependent influences on cell fate by assessing the effects of a lentivirally transduced constitutively activated Notch receptor on cell fate. At all ages studied, Notch activation resulted in a significantly greater number of GFAP-positive cells, seemingly overriding the greater neurogenic potential of younger stem cells. These data suggest that both extrinsic and intrinsic factors differentially regulate cell fate choices of progenitors during cortical development.
Control of Astrocyte Migration in the Developing Cerebral Cortex
Authors: Jacobsen Chad T. , Miller Robert H.
Published: September 2003

Development of the vertebrate central nervous system is characterized by significant long distance cell migration. While the radial migration of neuronal precursors to their final location is well established the migration of glial cells and their precursors is less well understood. To define the pathways of migration and dissect the cell and molecular mechanisms mediating such migration requires the development of appropriate models. Here we show that purified neonatal astrocytes injected into organotypic slice cultures of developing cerebral cortex migrate in defined patterns depending on where they are placed within the tissue. Injection into gray matter resulted in radially oriented migration either towards the pial or ventricular surface. By contrast injection into developing white matter resulted in largely longitudinal migration along developing axon tracts. While the cytoarchitecture of the tissue influenced the pattern of migration, the extent of migration appeared to be regulated primarily by the age of the host tissue. Homochronic injections performed prior to postnatal day 4 resulted in extensive migration while after day 7 migration was relatively limited. Heterochronic injections indicated that while astrocytes within the 1st postnatal week retained the capacity to migrate extensively, older tissue failed to support extensive migration of either young or old astrocytes. These data suggest the existence of distinct migrational cues in the CNS and that environmental, not cell intrinsic properties primarily regulate astrocyte migration through the developing cortex.
X-Ray Crystallographic and Theoretical Studies of an Anticonvulsant Enaminone: Methyl 4-(4’-Bromophenyl)amino-6-methyl-2-oxocyclohex-3-en-1-oate
Authors: Edafiogho I.O. , Denny B.J. , Schwalbe C.H. , Lowe P.R.
Published: September 2003

Objective: The aims of this study were to establish the structure of the potent anticonvulsant enaminone methyl 4-(4′-bromophenyl)amino-6-methyl-2-oxocyclohex-3-en-1-oate (E139), and to determine the energetically preferred conformation of the molecule, which is responsible for the biological activity. Materials and Methods: The structure of the molecule was determined by X-ray crystallography. Theoretical ab initio calculations with different basis sets were used to compare the energies of the different enantiomers and to other structurally related compounds. Results: The X-ray crystal structure revealed two independent molecules of E139, both with absolute configuration C11(S), C12(R), and their inverse. Ab initio calculations with the 6-31G, 3-21G and STO-3G basis sets confirmed that the C11(S), C12(R) enantiomer with both substituents equatorial had the lowest energy. Compared to relevant crystal structures, the geometry of the theoretical structures shows a longer C–N and shorter C=O distance with more cyclohexene ring puckering in the isolated molecule. Conclusion: Based on a pharmacophoric model it is suggested that the enaminone system HN–C=C–C=O and the 4-bromophenyl group in E139 are necessary to confer anticonvulsant property that could lead to the design of new and improved anticonvulsant agents.
Intravenous Sildenafil Is a Potent Pulmonary Vasodilator in Children With Congenital Heart Disease
Authors: Schulze-Neick Ingram , Hartenstein Paulina , Li Jia , Stiller Brigitte , Nagdyman Nicole , Hübler Michael , Butrous Ghazwan , Petros Andy , Lange Peter , Redington Andrew N.
Published: September 2003

Background—

Increased pulmonary vascular resistance (PVR) because of congenital heart disease (CHD) may be caused by a dysfunction in endogenous pulmonary endothelial nitric oxide (NO) production. In other forms of pulmonary vascular disease with increased PVR, an elevated activity of a phosphodiesterase type 5 (PDE-5), responsible for the degradation of cyclic guanidine monophosphate (cGMP), the second messenger of endothelially produced NO, has been demonstrated. This study compares the effects of inhaled NO before and after the specific inhibition of the PDE-5 by intravenous sildenafil (Viagra™) in pre- and postoperative children with increased PVR because of CHD.

Methods and Results—

12 children with congenital heart disease (age 0.2 to 15.7 years, median 2.4 years) and increased mean pulmonary arterial pressure, and 12 postoperative children (age 0.11 to 0.65 years, median 0.32 years) with increased PVR (8.3±1.0 Wood Units*m
2
) were studied during cardiac catheterization (“cath laboratory”), or within 2 hours after return from cardiac surgery (“post op”), respectively. All were sedated, tracheally intubated and paralyzed. During alveolar hyperoxygenation (F
i
O
2
=0.65), the effects of inhaled NO (20 ppm) were compared before and after the stepwise infusion of sildenafil (“cath laboratory”, 1 mg/kg; post op, 0.25 mg/kg). Intravenous sildenafil more effectively reduced PVR than NO (11.5% versus 4.3% in the “cath laboratory” patient group,
P
<0.05, and 25.8% versus 14.6% in the post op patient group,
P
=0.09. The increase in cGMP in response to NO was potentiated (2- to 2.4-fold) by PDE-5 inhibition. While the vasodilating effects of sildenafil showed pulmonary selectivity, its infusion was associated with increased intrapulmonary shunting in the postoperative patients (Q
s
/Q
t
=16.5±4.7% to 25.5±18.2%
P
=0.04).

Conclusions—

Intravenous sildenafil is as effective as inhaled NO as a pulmonary vasodilator in children with congenital heart disease. Although clinically insignificant in this study, increased intrapulmonary shunting with sildenafil may be disadvantageous in some patients after CHD surgery.
Impact of Preoperative Aortic Root Diameter on Long-Term Aortic Valve Function After Valve Sparing Aortic Root Reimplantation
Authors: Leyh R. G. , Kallenbach K. , Karck M. , Hagl C. , Fischer S. , Haverich A.
Published: September 2003

Background—

Valve sparing aortic root reimplantation technique in patients with aortic root aneurysm have shown excellent mid-term results. In conjunction with the diameter of the aortic root the mechanical leaflet stress increase, which might have an impact on long-term aortic valve function after valve sparing aortic root reimplantation.

Methods and Results—

From July 1993 to October 2001, 168 patients with aortic root aneurysm underwent valve sparing aortic root reimplantation. Patients with type A aortic dissection were excluded. Thus, 123 patients were analyzed. We identified 47 patients with an preoperative aortic root diameter exceeding 60 mm (group A), 58 patients with an diameter between 50 and 60 mm (group B), and 18 patients with a diameter less than 50 mm (group C). The groups were compared regarding mortality, long-term survival, freedom from reoperation, freedom from severe and moderate aortic valve insufficiency (AI), and postoperative morbidity. Mean follow-up (group A 43±26 months, group B 40±25 months, group C 23±19 months; group C versus group A,
P
=0.005; group C versus group B,
P
=0.011) was shorter in group C. Perioperative mortality (group A 2.2%, group B 1.9%, group C 5.2%;
P
=ns) was comparable between the groups with each one patient. The 3-year survival for group A was 98±2%, for group B 96±3%, and for group C 100±0% (
P
=ns). Freedom from reoperation for group A was 98±2%, for group B 96±3%, and for group C 88±8% (
P
=ns). Four patients developed severe or moderate AI, thus freedom from severe and moderate AI for group A was 100±0%, for group B 88±8%, and for group C 94±5% (
P
=ns). During follow-up no thromboembolic or bleeding events were noticed.

Conclusions—

Our data show that the preoperative diameter of the aortic root has no impact on the longevity of the repair. Thus, the reimplantation technique can be recommended for all patients presenting with an aortic root aneurysm and normal leaflets regardless of the aortic root diameter.
Midterm Results of the Ross Procedure Preserving the Patient’s Aortic Root
Authors: Sievers Hans- H. , Dahmen Gerlinde , Graf Bernhard , Stierle Ulrich , Ziegler Andreas , Schmidtke Claudia
Published: September 2003

Background—

Since the early 1990s, the pulmonary autograft is predominantly implanted as a freestanding root for less aortic valve regurgitation is reported. However, there is a certain risk of dilatation of the root over time potentially impairing valve function. We favor since 8 years the original subcoronary or inclusion technique to preserve the root of the patient as a restrain to dilatation.

Methods and Results—

Between June 1994 and May 2002 the subcoronary (n=228) and inclusion technique (n=17) were performed in 245 patients (191 male, 54 female), mean age 45.7±13.4 (15–70) years. The underlying aortic valve disease was an aortic insufficiency in n=83, stenosis in n=48, a combined aortic valve disease in n=111 and an acute endocarditis in n=19 patients. Previous aortic valve surgery was performed in n=23. Last follow-up investigations (within last year) including echocardiography was performed at a mean follow-up of 29.4±24.7 months (553.7 patient years). Hospital mortality was n=2, late mortality n=4 (all noncardiac). Two patients were lost to follow-up (99% complete clinical follow-up). Reoperations were necessary in n=7 valves (autograft: endocarditis n=1, malpositioning n=1, leaflet prolapse n=1; homograft: stenosis n=2, insufficiency n=2). Autograft insufficiency (AI) was AI 0 in n=154, AI I n=66, AI II n=8. The maximum/mean pressure gradient across the autograft was 6.6±3.4 (2.1 to 25.9)/3.6±1.8 (1.2 to 13.2) mm Hg, respectively. Homograft insufficiency was 0 in n=167, I in n=54, II in n=9, and III in n=1. Maximum and mean transhomograft pressure gradients were 11.7±6.8 (2.2 to 42.6)/6.2±3.8 (1.2 to 24.5) mm Hg. Most patients were NYHA class I (n=214), class II (n=19), class III (n=2). Significant aortic root dilatation was not observed.

Conclusions—

Aortic valve replacement with a pulmonary autograft in the subcoronary or inclusion technique provides excellent hemodynamics with no root dilatation at least in a mid term postoperative period. Transhomograft pressure gradients are slightly increased. Longer term results with special emphasis on the pulmonary homograft are necessary.
Off-Pump Coronary Artery Bypass Grafting Reduces Mortality and Stroke in Patients With Atheromatous Aortas: A Case Control Study
Authors: Sharony Ram , Bizekis Costas S. , Kanchuger Marc , Galloway Aubrey C. , Saunders Paul C. , Applebaum Robert , Schwartz Charles F. , Ribakove Greg H. , Culliford Alfred T. , Baumann F. Gregory , Kronzon Itzhak , Colvin Stephen B. , Grossi Eugene A.
Published: September 2003

Background—

Patients with severe atheromatous aortic disease (AAD) who undergo coronary artery bypass (CABG) have an increased risk of death and stroke. We hypothesized that in these high risk patients, off-pump coronary artery bypass (OPCAB) technique is associated with lower morbidity and mortality.

Methods and Results—

Between June 1993 and January 2002, 5737 patients undergoing CABG had routine intra-operative TEE with 913 (15.9%) found to have severe AAD in the aortic arch or ascending aorta. Of these, 211 patients who underwent OPCAB were matched with 211 on-pump CABG patients by age, ejection fraction, history of stroke, cerebrovascular disease, diabetes, renal disease, nonelective operation, and previous cardiac surgery. Hospital mortality was 11.4% (24/211) for on-pump CABG and 3.8% (8/211) for OPCAB (
P
=0.003). Multivariate analysis revealed that increased mortality was associated with on-pump CABG (
P
=0.001), acute MI (
P
=0.03), number of grafts (
P
=0.01), age (
P
=0.01), history of stroke or cerebrovascular disease (
P
=0.04), CHF (
P
=0.02), and peripheral vascular disease (
P
=0.03). Multivariate analysis showed that OPCAB technique was associated with decreased stroke (
P
=0.05). Freedom from any complication was 78.7% for on-pump CABG and 91.9% for OPCAB (
P
<0.001). At 36 month follow-up multivariate analysis revealed that increased mortality was associated with age (
P
=0.001), previous MI (
P
=0.03), and renal disease (
P
=0.04), whereas increased survival was associated with increased number of grafts (
P
=0.001) and OPCAB (
P
=0.01).

Conclusions—

OPCAB surgery in patients with severe AAD is associated with lower risk of death, stroke and complications and improved mid-term survival. Routine intra-operative TEE allows identification of these patients and directs choice of appropriate surgical technique.
Mitogen-Activated Protein Kinase Inhibition and Cardioplegia-Cardiopulmonary Bypass Reduce Coronary Myogenic Tone
Authors: Khan Tanveer A. , Bianchi Cesario , Ruel Marc , Voisine Pierre , Li Jianyi , Liddicoat John R. , Sellke Frank W.
Published: September 2003

Background—

Cardioplegia-cardiopulmonary bypass (C/CPB) is associated with coronary microcirculatory dysfunction. Regulation of the microcirculation includes myogenic tone. Mitogen-activated protein kinases (MAPK) have been implicated in coronary vasomotor function. We hypothesized that vasomotor dysfunction of the coronary microcirculation is mediated in part by alterations in extracellular signal regulated kinase 1/2 (ERK1/2) activity following C/CPB in humans.

Methods and Results—

Atrial myocardium was harvested from patients (n=15) before and after blood cardioplegia and short-term reperfusion under conditions of CPB. Myogenic tone of coronary arterioles was measured by videomicroscopy. Microvessel tone was determined post-C/CPB and after PD98059, a MAPK/ERK kinase 1/2 (MEK1/2) inhibitor. MAPK phosphatase-1 (MKP-1) and activated ERK1/2 were measured by Western blot. MKP-1 gene expression was determined by Northern blot. In situ hybridization and immunohistochemistry were used to localize myocardial MKP-1 and activated ERK1/2, respectively. Myogenic tone was reduced in coronary arterioles post-C/CPB (−10.5±0.9%,
P
<0.01 versus control/pre-C/CPB, n=5). Myogenic tone was decreased in coronary microvessels after 30 μmol/L (n=5) and 50 μmol/L (n=5) PD98059 treatment (−11.0±0.8% and −14.6±2.0%, respectively, both
P
<0.01 versus control/pre-C/CPB). Myocardial levels of activated ERK1/2 were reduced post-C/CPB (0.6±0.1, post/pre-C/CPB ratio,
P
<0.05, n=5) while MKP-1 levels increased (4.2±0.6, post/pre-C/CPB ratio,
P
<0.05, n=5). Myocardial MKP-1 gene expression increased post-C/CPB (3.0±0.8, post/pre-C/CPB ratio,
P
<0.05, n=5). MKP-1 and activated ERK1/2 localized to coronary arterioles in myocardial sections.

Conculsions—

Coronary myogenic tone is dependent on ERK1/2 and decreased after C/CPB. C/CPB reduces levels of activated ERK1/2, potentially by increased levels of MKP-1. The ERK1/2 signal transduction pathway in part mediates coronary microvascular dysfunction after C/CPB in humans.