bluuebunny/crossref_metadata_2025 huggingface dataset:
Global optimization of cerebral cortex layout
Authors: Cherniak Christopher , Mokhtarzada Zekeria , Rodriguez-Esteban Raul , Changizi Kelly
Published: January 2004

Functional areas of mammalian cerebral cortex seem positioned to minimize costs of their interconnections, down to a best-in-a-billion optimality level. The optimization problem here, originating in microcircuit design, is: Given connections among components, what is the physical placement of the components on a surface that minimizes total length of connections? Because of unfeasibility of measuring long-range “wire length” in the cortex, a simpler adjacency cost was validated. To deal with incomplete information on brain networks, a size law was developed that predicts optimization patterns in subnetworks. Macaque and cat cortex rank better in this connection optimization than the wiring of comparably structured computer chips, but somewhat worse than the macroeconomic commodity-flow network among U.S. states. However, cortex wiring conforms to the size law better than the macroeconomic patterns, which may indicate cortex optimizing mechanisms involve more global processes.
The evolution of transmembrane helix kinks and the structural diversity of G protein-coupled receptors
Authors: Yohannan Sarah , Faham Salem , Yang Duan , Whitelegge Julian P. , Bowie James U.
Published: January 2004

One of the hallmarks of membrane protein structure is the high frequency of transmembrane helix kinks, which commonly occur at proline residues. Because the proline side chain usually precludes normal helix geometry, it is reasonable to expect that proline residues generate these kinks. We observe, however, that the three prolines in bacteriorhodopsin transmembrane helices can be changed to alanine with little structural consequences. This finding leads to a conundrum: if proline is not required for helix bending, why are prolines commonly present at bends in transmembrane helices? We propose an evolutionary hypothesis in which a mutation to proline initially induces the kink. The resulting packing defects are later repaired by further mutation, thereby locking the kink in the structure. Thus, most prolines in extant proteins can be removed without major structural consequences. We further propose that nonproline kinks are places where vestigial prolines were later removed during evolution. Consistent with this hypothesis, at 14 of 17 nonproline kinks in membrane proteins of known structure, we find prolines in homologous sequences. Our analysis allows us to predict kink positions with >90% reliability. Kink prediction indicates that different G protein-coupled receptor proteins have different kink patterns and therefore different structures.
Visualization of spatially and temporally regulated N-WASP activity during cytoskeletal reorganization in living cells
Authors: Ward Michael E. , Wu Jane Y. , Rao Yi
Published: January 2004

Members of the WASP/WAVE family of proteins are key regulators of cytoskeletal reorganization across a diverse range of cellular processes. Despite a wealth of biochemical data about WASP/WAVE regulation
in vitro
, our understanding of the
in vivo
regulation of these proteins is hampered by the inability to monitor subcellular regulation of their activities in living cells. Here we establish a fluorescence resonance energy transfer-based approach to visualize spatial and temporal regulation of neuronal Wiskott–Aldrich syndrome protein (N-WASP) activity in living cells. Using time-lapse microscopy, we characterize the activation of N-WASP in response to growth-factor stimulation, and we reveal that N-WASP is activated inside extending filopodia. Furthermore, we suggest a role of N-WASP in regulating membrane ruffling downstream of phosphatidylinositol 4,5-bisphosphate and Cdc42.
A structure-based model for ligand binding and dimerization of EGF receptors
Authors: Klein Peter , Mattoon Dawn , Lemmon Mark A. , Schlessinger Joseph
Published: January 2004

On the basis of the 3D structures of the extracellular ligand-binding domains of the epidermal growth factor (EGF) receptor (EGFR) and ErbB3, a mechanism has been proposed for how the extracellular region of the EGFR is maintained in an autoinhibited configuration and for how EGF binding induces EGFR dimerization and activation. We have attempted to derive a mathematical model for EGF binding to the EGFR and for ligand-induced receptor dimerization and activation that uses this structural information and can explain the characteristic concave-up curvilinear Scatchard plots seen when EGF binding to intact EGFR is studied in living cells. We show that these curvilinear plots cannot be accounted for by simply ascribing different affinities to the autoinhibited and extended (dimeric) configurations of the receptor seen in structural studies. Concave-up plots can only be obtained by including in the mathematical model an additional binding event in which occupied EGFR dimers bind to an “external site.” The external site may represent receptor interactions with coated-pit regions in the cell membrane or with other cellular components involved in receptor endocytosis and turnover. We conclude in this study and in the accompanying article that the active extended EGFR configuration binds EGF 5- to 20-fold more strongly than the autoinhibited monomeric receptor configuration. However, these extended receptors do not correspond directly with the “high-affinity” EGF-binding sites seen in EGF-binding studies on intact cells.
Complex and dynamic redistribution of NF-κB signaling intermediates in response to T cell receptor stimulation
Authors: Schaefer Brian C. , Kappler John W. , Kupfer Abraham , Marrack Philippa
Published: January 2004

The central zone of the supramolecular activation cluster (c-SMAC) is a zone of T cell receptor (TCR) enrichment that forms at a T cell/antigen-presenting cell (APC) junction in response to antigen stimulation. We demonstrate that there is a surprisingly complex relocalization process that brings PKCθ and Bcl10, two intermediates in TCR activation of NF-κB, to the cytoplasmic face of the c-SMAC. TCR activation causes enrichment of PKCθ at the c-SMAC, followed by Bcl10 relocalization to punctate cytoplasmic structures, often at sites distant from the c-SMAC. These Bcl10 structures then undergo further relocalization, becoming enriched at the c-SMAC. TCR activation of NF-κB therefore involves the dynamic relocalization of multiple signaling intermediates, with distinct phases proximal to and distant from the c-SMAC.
Simian virus 40 large T antigen targets the spindle assembly checkpoint protein Bub1
Authors: Cotsiki Marina , Lock Rowena L. , Cheng Yuan , Williams Grace L. , Zhao Jean , Perera David , Freire Raimundo , Entwistle Alan , Golemis Erica A. , Roberts Thomas M. , Jat Parmjit S. , Gjoerup Ole V.
Published: January 2004

The mitotic spindle checkpoint protein Bub1 has been found to be mutated at low frequency in certain human cancers characterized by aneuploidy. Simian virus 40 large T antigen efficiently immortalizes rodent cells and occasionally transforms them to tumorigenicity. T antigen can also cause genomic instability, inducing chromosomal aberrations and aneuploidy. Here, we report an interaction between Bub1 and T antigen. T antigen coimmunoprecipitates with endogenous Bub1 and Bub3, another component of the spindle checkpoint complex. Genetic analysis demonstrates that the interaction of T antigen with Bub1 is not required for immortalization but is closely correlated with transformation. T antigen induces an override of the spindle checkpoint dependent on Bub1 binding. This interaction with proteins of the spindle checkpoint machinery suggests another role for T antigen and provides insight into its ability to cause chromosomal aberrations, aneuploidy, and transformation.
Mutations arising in the wave front of an expanding population
Authors: Edmonds Christopher A. , Lillie Anita S. , Cavalli-Sforza L. Luca
Published: January 2004

The ability to infer the time and place of origin of a mutation can be very useful when reconstructing the evolutionary histories of populations and species. We use forward computer simulations of population growth, migration, and mutation in an analysis of an expanding population with a wave front that advances at a constant slow rate. A pronounced founder effect can be observed among mutations arising in this wave front where extreme population bottlenecks arise and are followed by major population growth. A fraction of mutations travel with the wave front and generate mutant populations that are on average much larger than those that remain stationary. Analysis of the diffusion of these mutants makes it possible to reconstruct migratory trajectories during population expansions, thus helping us better understand observed patterns in the evolution of species such as modern humans. Examination of some historical data supports our model.
The ability of habitual exercise to influence appetite and food intake in response to high- and low-energy preloads in man
Authors: Long S. J. , Hart K. , Morgan L. M.
Published: January 2004

The present study tested the hypothesis that habitual exercisers demonstrate an increased accuracy of regulation of food intake in compensation for previous dietary energy intake. Twenty-three lean healthy male subjects were divided into two groups on the basis of their habitual exercise levels: non-exercisers (no exercise sessions/week, n 9), and exercisers (>two exercise sessions of 40 min or more/week, n 14). The appetite response to covert liquid preloads of high (2513 kJ) energy (HE) and low (1008 kJ) energy (LE) was investigated Sixty minutes after the preload subjects were offered an ab libitum buffet-style meal and energy intake (EI) was calculated. Subjective hunger and satiety were assessed throughout using self-rated visual-analogue scales. Buffet EI in non-exercisers was not significantly different following the LE or HE preloads (mean compensation 7 %), but the exercise group significantly reduced their energy intake following the HE, compared with the LE, preload (mean compensation 90 %; P=0·0035). A broadly similar pattern of response was observed for both moderate (two to three sessions/week, n 7) and high exercisers (>four sessions/week, n 7). There were no significant differences between hunger or satiety ratings following HE or LE preloads for either group. However non-exercisers scored significantly higher on their self-ratings of hunger at the start of the study, before preload consumption, compared with the exercisers (P<0·01). These findings demonstrate that habitual exercisers have an increased accuracy of short-term regulation of food intake in compensation for preload manipulation, and provide additional support for advocating regular exercise in the prevention of overweight and obesity.
Intestinal microflora of human infants and current trends for its nutritional modulation
Authors: Mountzouris Konstantinos C. , McCartney Anne L. , Gibson Glenn R.
Published: January 2004

Diet, among other environmental and genetic factors, is currently recognised to have an important role in health and disease. There is increasing evidence that the human colonic microbiota can contribute positively towards host nutrition and health. As such, dietary modulation has been proposed as important for improved gut health, especially during the highly sensitive stage of infancy. Differences in gut microflora composition and incidence of infection occur between breast- and formula-fed infants. Human milk components that cannot be duplicated in infant formulae could possibly account for these differences. However, various functional food ingredients such as oligosaccharides, prebiotics, proteins and probiotics could effect a beneficial modification in the composition and activities of gut microflora of infants. The aim of the present review is to describe existing knowledge on the composition and metabolic activities of the gastrointestinal microflora of human infants and discuss various possibilities and opportunities for its nutritional modulation.
β-Carotene and α-tocopherol concentration and antioxidant status in buccal mucosal cells and plasma after oral supplementation
Authors: Erhardt Jürgen G. , Mack Heidrun , Sobeck Ulrike , Biesalski Hans K.
Published: January 2004

The uptake of α-tocopherol and β-carotene and their antioxidative effect in plasma and buccal mucosal cells after oral application in twelve subjects is demonstrated in our study. The effect on the antioxidative status was evaluated using a modified thiobarbituric acid-reactive substance (TBARS) method. As expected, the supplement of 134·2 mg α-tocopherol/d and 25 mg β-carotene/d for 7 d resulted in a significant increase of α-tocopherol and β-carotene concentration in plasma (P<0·05). In buccal mucosal cells, the concentration of β-carotene increased after supplementation (P<0·05), whereas the concentration of α-tocopherol remained constant. A decrease in TBARS (P<0·05) was found in buccal mucosal cells but not in plasma. In conclusion, an uptake of the supplemented antioxidants was detected in plasma and in buccal mucosal cells. There was significant change in β-carotene concentration and oxidative stress as measured using a modified TBARS test in buccal mucosal cells, but not in the plasma.
Evidence that dietary supplementation with carotenoids and carotenoid-rich foods modulates the DNA damage:repair balance in human lymphocytes
Authors: Astley Siân B. , Elliott Ruan M. , Archer David B. , Southon Susan
Published: January 2004

Epidemiological evidence has shown that the habitual consumption of diets high in fruits and vegetables is associated with reduced risk of cancers. The challenge is to identify causal mechanisms of effect. The aim of the current study was to determine whether an increase in rate of removal of DNA single-strand breaks (SSB) following oxidative challenge could be provokedex vivoin peripheral blood lymphocytes (PBL). The PBL were isolated from apparently healthy volunteers following dietary intervention with: (1) a mixed carotene capsule; (2) a daily portion of cooked minced carrots; (3) a matched placebo; (4) a portion of mandarin oranges; (5) vitamin C tablets. Single-cell gel electrophoresis was employed to measure baseline levels of SSB and DNA susceptibility to oxidative damage, and to monitor the number of SSB over 4 h, in both unchallenged and H2O2-treated PBL. The enzymatic capacity for repair of different types of DNA oxidative lesions was also measured using two related cell-free assays. There was no evidence that any of the dietary supplementation regimens altered baseline levels of SSB, provided any direct antioxidant protection or altered DNA repair capacity, with two exceptions: the number of SSB following exposure to H2O2decreased more rapidly in PBL from volunteers given the mixed carotene capsules and repair patch synthesis activity in PBL increased from volunteers given the cooked carrots. These results suggest that carotenoids and carotenoid-rich foods can influence DNA damage:repair by modulation of discrete stages in the DNA repair mechanisms.
Lack of dose-responsive effect of dietary phyto-oestrogens on transepithelial calcium transport in human intestinal-like Caco-2 cells
Authors: Cotter Alice A. , Cashman Kevin D.
Published: January 2004

Ca absorption has been shown to be unaffected by high luminal concentrations of two commonly consumed soyabean phyto-oestrogens (PO) (genistein and daidzein) in Caco-2 cells grown under oestrogen-depleted conditions. However, these compounds exhibit dose-dependent biphasic effects in some tissues, such as reproductive tissue and bone. Thus, in light of this biphasic activity, the effect of lower concentrations of genistein and daidzein on Ca absorption requires further investigation. Therefore, the aim of the present study was to investigate the effect of a range of concentrations of genistein and daidzein on Ca absorption in the human Caco-2 intestinal-like cell model. Caco-2 cells were seeded onto permeable filter supports and allowed to differentiate into monolayers. On day 21, the Caco-2 monolayers (n 12 per treatment), grown in oestrogen-deplete media, were then exposed to 10 nm-1,25-dihydroxycholecalciferol (1,25 (OH)2D3), or 1, 10 and 50 μm-genistein or -daidzein for 24 h. After exposure, transepithelial and transcellular transport of 45Ca and fluorescein transport were measured. As expected, 1,25 (OH)2D3 stimulated Ca absorption in Caco-2 cells, by up regulating transcellular transport. Ca absorption was unaffected by either PO at luminal concentrations of 1, 10 or 50 μm, typical of intakes by Western and Asian populations as well as supplemental levels, respectively. The results of this model suggest that the proposed beneficial effects of supplemental levels of these PO compounds on bone mass in postmenopausal women more probably arise from direct effects on bone cells, and not by an indirect effect of these compounds on Ca absorption.
Hot‐Extruded and Cold‐Rolled Textures of the Matrix Aluminum in Deformation Processed Two‐Phase Nb/Al Metal‐Metal Composites
Authors: Chen L. Q. , Kanetake N.
Published: January 2004

In this article, the powder metallurgy technique combined with flat hot‐extrusion and cold rolling processes
was employed to fabricate 10 and 20vol.%Nb/Al metal–metal composite sheets. The hot‐extruded and coldrolled
textures of the matrix aluminum in these metal–metal composite sheets were investigated by three
dimensional orientation distribution functions (ODFs) analysis. The results show that the extrusion mode
and large second phase particulate metal, Nb, have strong influence on the development of the extrusion
and cold rolling textures in composites’ matrix. The matrix Al forms β‐fiber textures after flat hot extrusion,
where the components consist of B′‐{011} ‹322›, S′‐{124} ‹654› and C′‐{113}h332i. After cold rolling process, only B′‐{011} ‹322› changed to B‐{011} ‹211› while the other components remained the same. The large particles in composites affect the matrix deformation in such a way that separates the distorted or bound zones
from the deformation zones, which resulted in the final cold rolling deformation textures.
Intensity Correction in Texture Measurement of Polycrystalline Thin Films by X‐Ray Diffraction
Authors: Liu Y. S. , Depre L. , De Buyser L. , Wu T. B. , Van Houtte P.
Published: January 2004

The tilting of a specimen may not only result in defocusing effect, but also in a change of irradiated volume
during texture measurement for thin films and coatings by using X‐ray diffraction. The influence on diffraction
intensity has to be considered in order to obtain an accurate result of texture analysis. The effect of irradiated
volume can be formulated as a function of the thickness and the linear absorption of a studied film
material, the tilt angle of the specimen and the Bragg angle of diffraction, and then eliminated. In view of
that the preparation of a randomly oriented specimen would be difficult, a simple and convenient method
is hereby proposed to correct the defocusing effect from known data of existing bulk powder specimens
with random orientation by interpolation (or extrapolation). The two correction methods were experimentally
verified to be effective and reliable.
Full Stress Tensor Determination in A textured Aerospace Aluminium Alloy Plate Using synchrotron X‐Ray Diffraction
Authors: Stelmukh V. , Edwards L. , Ganguly S.
Published: January 2004

Triaxial strain scanning has been performed on a 7mm thick 7150‐aluminium alloy Variable Polarity Plasma
Arc (VPPA) weld using synchrotron X‐rays. It has been demonstrated that the use of specific advantageous
(hkl) peaks that occur in this highly textured aerospace alloy plate permits fast deep measurements in reflection
as well as in transmission. The sin⁡2ψ method was also utilised to monitor the variation in deviatoric stress
component (σ11 − σ33) across the weld in both the test‐piece and a comb like reference specimen used to map the
changes in stress‐free lattice spacings over the weld. The results suggest that microstresses have little effect on
macrostress determination, particularly in the Heat Affected Zones (HAZ). Though small in magnitude, the
macrostresses still present in the reference specimen can be allowed for to correct the stress tensor in the plate.
Maximum tensile longitudinal stress values remain unchanged, whereas the stress condition in some parts of
the HAZ is well described as biaxial after the proposed correction.
Tensile Deformation Induced Texture Transformation in Austenitic Stainless Steel
Authors: Grigull S.
Published: January 2004

Texture patterns of the starting ώ and transformed α structural phases were obtained from AISI 304 stainless
steel sheets subjected to varying levels of tensile deformation using high energy X‐ray diffraction in combination
with the texture enhanced Rietveld method. The use of this method allows the simultaneous determination
of the orientation distribution functions (ODF) of both phases, even for small α‐martensite fractions of
the order of 5%. The texture patterns are analyzed in terms of the crystallographic orientation relation
between the starting and transformed phases and the preferential formation of certain variants of this relation.
Depth Resolved Strain and Phase Mapping of Dissimilar Friction Stir Welds Using High Energy Synchrotron Radiation
Authors: Martins R. V. , Honkimäki V.
Published: January 2004

The strain and phase distribution in a dissimilar friction stir weld of AA6082‐T6 to AA2024‐T3 is investigated
non‐destructively. The measurements are performed using a novel depth resolved strain and phase mapping
technique. The technique is based on the use of a focussed high energy synchrotron beam, a novel spiral slit
system, and an area detector system. Through thickness measurements of the residual strain along the weld
centre show strong variations with changes of sign. The strain scans across the weld exhibit a strong asymmetry
in particular for the longitudinal strain component. A depth resolved strain mapping across the weld
shows for the dominant longitudinal strain component variations in depth, especially on the AA6082 side
of the weld. Results from the strain measurements are related to the depth resolved map of the material
distribution in the weld zone.
Torsion Texture Measurements With High‐Energy Synchrotron Radiation on NiAl
Authors: Skrotzki W. , Klöden B. , Tamm R. , Oertel C.-G. , Garbe U. , Rybacki E.
Published: January 2004

Diffraction with high‐energy synchrotron radiation is a new experimental method to determine textures of
materials, which due to the special properties of this radiation, in the future may have advantages in terms
of accuracy of local texture measurements in comparison to established methods like Electron back scatter
diffraction (EBSD). In the present study NiAl polycrystals with two different initial textures have been
deformed in torsion at 727°C and 1000°C and their texture development has been measured with highenergy
synchrotron radiation. Torsion enables the study of texture formation with strain as well as the
exploration of large strains without changing the shape of the samples. The pole figures indicate the preferred
alignment of ‹100› with the shear direction and {110} with the shear plane. High pressure torsion may also
open new possibilities in terms of grain refinement and texture formation and thus ductilization of NiAl.
Influence of Grain Number on Graphite Quantitative Texture Study
Authors: Lychagina T. A. , Nikolayev D. I.
Published: January 2004

The present work is devoted to the study of the grain number influence on the quantitative texture analysis
and on the values of averaged elastic properties. Number of grains does not influence mathematical definition
of orientation distribution function (ODF) (Bunge, H.J. (1982). Texture Analysis in Material Science.
Butterworths, London; Matthies, S., Vinel, G.W. and Helming, K. (1987). Standard Distributions in
Texture Analysis. Akademie‐Verlag, Berlin.); nevertheless, intuitively clear that, averaging procedure implies
a ‘‘large’’ number of grains to make sense. In the present work we applied the already suggested procedure
(Lychagina, T.A. and Nikolayev, D.I. (2003). Phys. Stat. Sol. (a), 195(N2), 322–334.) for the case of hexagonal
symmetry to evaluate the influence of the grain number in the sample on the calculated elastic properties.
This procedure was carried out for graphite that is one of the widespread, applicable and highly anisotropic
materials.
High‐Energy X‐Rays: A tool for Advanced Bulk Investigations in Materials Science and Physics
Authors: Liss Klaus-Dieter , Bartels Arno , Schreyer Andreas , Clemens Helmut
Published: January 2004

High‐energy X‐rays between 30 keV and 1MeV, such as provided by modern synchrotron radiation sources as
the ESRF and HASYLAB, bear the advantage of high penetration into most materials. Even heavy element
compositions can be accessed in their volume. The range of applications is huge and spreads from nuclear
spectroscopy to the characterization of metal extrusion under industrial conditions. This article compiles
an overview over the most common instrumental diffraction techniques.

Modern two‐dimensional detectors are used to obtain rapid overviews in reciprocal space. For example,
diffuse scattering investigations benefit from the very flat Ewald sphere as compared to low energies,
which allow mapping of several Brillouin zones within one single shot. Diffraction profiles from liquids or
amorphous materials can be recorded easily. For materials science purposes, whole sets of Debye–Scherrer
rings are registered onto the detector, their diameters and eccentricities or their intensity distribution along
the rings relating to anisotropic strain or texture measurements, respectively. At this point we stress the resolution
of this technique which has to be carefully taken into account when working on a second generation
synchrotron source.

Energy‐dispersive studies of local residual strain can be studied by a dedicated three‐circle diffractometer
which allows accurately to adjust the scattering angle from a defined gauge volume.

Triple axis diffractometry and reciprocal space mapping is introduced and can be employed for highest
resolution purposes on single crystal characterization, even under heavy and dense sample environments.
Thus, the perfection of single crystals can be mapped and strain fields and superstructures as introduced
by the modulation from ultrasonic waves into crystals or epitaxially grown Si/Ge layers can be investigated
in detail. Phase transitions as magnetic ordering can be studied directly or through its coupling to the crystal
lattice. Time resolved studies are performed stroboscopically from a sub‐nanosecond to a second time scale.

The combination of these techniques is a strong issue for the construction and development of future
instruments.
Use of Synchrotron Diffraction Data for Describing Crystal Structure and Crystallographic Phase Analysis of R‐Phase NiTi Shape Memory Alloy
Authors: Sitepu Husin
Published: January 2004

Sitepu et al. (Sitepu, H., Schmahl, W.W., Khalil Allafi, J., Eggeler, G., Dlouhy, A., Reinecke, T., Brokmeier,
H.G., Tovar M. and Többens, D.M. (2002b). Texture and quantitative phase analysis of aged Ni‐rich NiTi
using X‐ray and neutron diffractions. Materials Science Forum, 394‐395, 237‐240.) showed that Rietveld
refinement with generalized spherical harmonic (GSH) description for neutron powder diffraction (ND)
data of the aged (673 K, 20 h) Ni‐rich NiTi shape memory alloy (Sitepu H. (2002). Assessment of preferred
orientation with neutron powder diffraction data. J. Appl. Cryst, 35, 274–277); of nominal composition
50.7 at.% Ni at 294K consists of four phases: precipitate (Ni4Ti3), R‐phase, monoclinic (B19′) and some residual
cubic (B2). Therefore, they concluded that the differential scanning calorimetry (DSC) first peak, on
cooling, (321 K) is not due to the formation of the R‐phase alone. The second, lower DSC peak (271 K) is
due to the transformation of R‐phase and residual B2 phase to B19′ phase. The structural refinement of
R‐phase problem, which was neglected in the previous study, was undertaken with great care in this study.
The objective of the present article is to use the third generation synchrotron X‐ray source at the
European Synchrotron Research Facility (ESRF) in Grenoble, which make available X‐ray beams of
higher energy and much higher intensity than laboratory X‐ray sources, for describing crystal structure of
the R‐phase in 50.75 at.% Ti–47.75 at.% Ni–1.50 at.% Fe ternary alloy. The synchrotron diffraction data
of R‐phase were analyzed using the Rietveld refinement with GSH description. The results showed that no
significant improvement in fit is found when the inversion center is removed from the model, suggesting that the space group is indeed
and not P3.
High‐Resolution Imaging of Texture and Microstructure by the Moving Detector Method
Authors: Bunge H. J. , Klein H. , Wcislak L. , Garbe U. , Weiß W. , Schneider J. R.
Published: January 2004

In order to describe texture and microstructure of a polycrystalline material completely, crystal orientation
g = {ϕ1Φϕ2} must be known in all points x = {x1 x2 x3} of the material. This can be achieved by locationresolved
diffraction of high‐energy, i.e. short‐wave, X‐rays from synchrotron sources. Highest resolution in
the orientation‐ as well as the location‐coordinates can be achieved by three variants of a detector “sweeping”
technique in which an area detector is continuously moved during exposure. This technique results in
two‐dimensionally continuous images which are sections and projections of the six‐dimensional “orientation–
location” space. Further evaluation of these images depends on whether individual grains are resolved
in them or not. Because of the high penetration depth of high‐energy synchrotron radiation in matter, this
technique is also, and particularly, suitable for the investigation of the interior of big samples.
Applications on High‐Energy X‐Rays to Stress Measurements of Thermal Barrier Coatings
Authors: Suzuki Kenji , Tanaka Keisuke
Published: January 2004

High‐energy X‐rays from a synchrotron radiation source, SPring‐8, were applied to the stress measurements
of thermal barrier coating (TBC). The specimen had a zirconia top coat on a bond coat of NiCoCrAlY
sprayed on the substrate of Ni‐base super alloys. The stress in the bond coat was measured through the
top coat using the diffraction of Ni3Al 311 by high‐energy X‐rays with an energy of 72 keV. The sin2ψ method was used to determine the stress value. A specially designed furnace with a wide beryllium window
was developed to conduct in-situ measurements of the internal stress in the bond coating at the room temperature,
773, 1073, and 1373 K. The internal stress was tensile at the room temperature, and decreased with
increasing temperature. At 1073K or higher, the internal stress in the bond coat was released due to softening
of the bond coat. The normal stress perpendicular to the coating surface of TBC was evaluated by a new
hybrid method. Since the penetration depth of low‐energy X‐ray is very small around a few micrometers
for zirconia, the stress value measured by the sin2ψ method is the in‐plane stress, σ1, and the stress perpendicular
to the surface was zero. On the other hand, the penetration depth of high‐energy X‐rays is very deep,
so the measured stress value will be the in‐plane stress minus the out‐of‐plane stress, i.e. σ1 − σ3. The normal
stress perpendicular to the surface, σ3, i.e. the spalling stress, was estimated from these two measurements.
The specimens were exposed in air atmosphere at 1373 K for 500, 1000, and 2000 h. The distribution of the
spalling stress in the top coat was estimated by the hybrid method. The spalling stress near the interface to
the bond coat changed to a large tension after long‐time exposure.
Effect of Gravity on the Kinetics of Consolidation of Powder Bodies
Authors: Kadushnikov R. M. , Nurkanov E. Y. , Shak A. V. , Petrov M. S. , Kartashov V. V.
Published: January 2004

Physical mathematical model of sintering powders is suggested with respect to the influence of gravitation on
sintering kinetics. Structure genesis and evolution in sintered glass‐based particulate bodies is investigated
both in computer simulations and “in situ”.
Drug/substance reversal effects of a novel tri‐substituted benzoflavone moiety (BZF) isolated from Passiflora incarnata Linn.–a brief perspective
Authors: Dhawan Kamaldeep
Published: January 2004

The present work is a mini‐review of the author's original work on the plant Passiflora incarnata Linn., which is used in several parts of the world as a traditional medicine for the management of anxiety, insomnia, epilepsy and morphine addiction. A tri‐substituted benzoflavone moiety (BZF) has been isolated from the bioactive methanol extract of this plant, which has been proposed in the author's earlier work to be responsible for the biological activities of this plant. The BZF moiety has exhibited significantly encouraging results in the reversal of tolerance and dependence of several addiction‐prone psychotropic drugs, including morphine, nicotine, ethanol, diazepam and delta‐9‐tetrahydrocannabinol, during earlier pharmacological studies conducted by the author. In addition to this, the BZF moiety has exhibited aphrodisiac, libido‐enhancing and virility‐enhancing properties in 2‐year‐old male rats. When administered concomitantly with nicotine, ethanol and delta‐9‐tetrahydrocannabinol for 30 days in male rats, the BZF also prevented the drug‐induced decline in sexuality in male rats. Because the BZF moiety isolated from P. incarnata is a tri‐substituted derivative of alpha‐naphthoflavone (7,8‐benzoflavone), a well‐known aromatase‐enzyme inhibitor, the mode of action of BZF has been postulated to be a neurosteroidal mechanism vide in which the BZF moiety prevents the metabolic degradation of testosterone and upregulates blood‐testosterone levels in the body. As several flavonoids (e.g. chrysin, apigenin) and other phytoconstituents also possess aromatase‐inhibiting properties, and the IC 50 value of such phytomoieties is the main factor determining their biochemical efficacy, by altering their chemical structures to attain a desirable IC 50 value new insights in medical therapeutics can be attained, keeping in view the menace of drug abuse worldwide.
Maintenance treatment with depot opioid antagonists in subcutaneous implants: an alternative in the treatment of opioid dependence
Authors: Carreño JE , Alvarez CE , San Narciso GI , Bascarán MT , Díaz M , Bobes J
Published: January 2004

A report is presented of treatment of 156 patients (male 98%) with opioid dependence (ICD‐10 criteria) using a maintenance programme with depot opioid antagonists (naltrexone) as subcutaneous implants, started after an outpatient rapid antagonization regimen. The retention index in the treatment was from 80% in the sixth month, and 65% after one year. The patients were followed‐up for 1 year after discharge. For 6 months after discharge 55.4% were still returning for follow‐up visits and 20.8% after 1 year, all of them remaining abstinent to opioids. It is concluded that the programme is safe for the patients and shows a better retention index than programmes using oral antagonists, with an improved compliance (negative urine analysis) compared to the latter.
An audit of the effectiveness of amphetamine isomer ratios as a marker of Dexedrine? compliance in amphetamine abusers
Authors: George S
Published: January 2004

The effectiveness of using amphetamine isomer ratios to determine individual compliance with a Dexedrine? (dexamphetamine, Celltech, Slough, UK) treatment regimen for the maintenance and detoxification from amphetamine abuse has been audited. The calculation of l/d‐amphetamine isomer ratios in urine has been shown previously to provide an accurate method for determining the compliance of subjects prescribed dexamphetamine. This audit was performed on the results obtained subsequent to the analysis of 369 urine specimens collected from 87 subjects (26 female, 61 male), all prescribed dexamphetamine collected from January 1999 to December 2002. The analysis was performed using a chiral derivatizing agent in conjunction with a gas chromatograph fitted with a mass spectrometer. It was found that only 245 specimens (66%) were deemed to be from compliant subjects. Of the remainder, 60 (16%) were collected when subjects were apparently supplementing their dexamphetamine prescription with illicit amphetamine, and 66 (18%) were collected when subjects were apparently using primarily illicit amphetamine. In summary, a sensitive and specific technique has been developed and applied to the analysis of urine specimens obtained from those prescribed dexamphetamine to facilitate the monitoring of their compliance. It is hoped that this technique may continue to be used to audit further the treatment in these individuals in the future to optimize their management.
Alcohol beverages and biochemical changes in blood
Authors: Gorinstein Shela , Trakhtenberg Simon
Published: January 2004

Coronary atherosclerosis is the major cause of death in western civilization: one of every three in men as well as in women. It was shown that diets supplemented with moderate quantities of alcoholic beverages could lead to positive biochemical changes in blood of the consumers, which are regarded widely as indicators of improved prevention of atherosclerosis. This review summarizes the recent epidemiological, experimental and clinical investigations concerning mainly the plasma biochemical changes in lipid levels, anticoagulant and antioxidant activities.
Sequential studies of sleep disturbance and quality of life in abstaining alcoholics
Authors: Cohn TJ , Foster JH , Peters TJ
Published: January 2004

Previous studies in recently detoxified dependent alcoholics have shown severely disturbed sleep and impaired quality of life. Although this association has been found to predict short‐term relapse to heavy drinking, no sequential studies have been conducted to monitor significant changes in sleep quality and quality of life in abstaining alcoholics. Fifty‐seven inpatients at a voluntary sector 12‐Step alcohol detoxification unit in South London were administered a series of questionnaires assessing sleep (Pittsburgh Sleep Quality Index, PSQI), Quality of Life (Euro‐Qol) and Depression and Anxiety (Hospital Anxiety and Depression Scales, HADS). Questionnaires were administered at baseline and for 12 weeks at monthly intervals. At baseline, PSQI scores showed that 52 of the 57 participants suffered from impaired sleep. The scores, however, did not correlate significantly with any of the other measurements. All except two participants acknowledged impaired Quality of Life in at least one area. With respect to the follow‐up measurements 23 (40%) participants completed the study. Quality of life and depression scores improved significantly over a 12‐week period but sleep and anxiety scores did not. At 12 weeks the mean PSQI score was still above the cut‐off point for ‘sleep caseness’. Quality of life and depression show a significant improvement over a 3‐month period of abstinence, although at this point the subjects are still experiencing difficulties with sleep and anxiety. This information could help in the planning of future rehabilitation and treatment programmes.
Brain mitochondrial aldehyde dehydrogenase: relation to acetaldehyde aversion in low‐alcohol‐drinking (UChA) and high‐alcohol‐drinking (UChB) rats
Authors: Quintanilla María elena , Tampier Lutske
Published: January 2004

Previous reports indicate that the low‐drinker (UChA) rats, when compared to high‐drinker (UChB) rats, display lower mitochondrial aldehyde dehydrogenase (ALDH2) activity due to a mutation of the Aldh2 gene. Because a later study found line differences in sensitivity to the aversive effects of acetaldehyde (AcH) administered intraperitoneally (i.p.), which were not associated with the line difference detected in blood AcH levels, the present study examined the contribution of brain ALDH2 activity to AcH aversion in UChA and UChB rats. In experiment 1, we established the dose‐response curves for AcH aversion (25, 50 or 100 mg/kg i.p.) in rats of both lines by using a conditioned taste aversion (CTA) paradigm. The results confirm our previous finding that UChA and UChB rats presented marked differences in their AcH aversion thresholds, which were not associated with the line differences detected in blood AcH levels. In experiment 2, the possibility that the inhibition of the brain ALDH2 would lower the AcH aversion threshold in both lines was studied by determining the effect of cyanamide (10 mg/kg i.p.) pretreatment, an inhibitor of ALDH, on AcH aversion, blood AcH levels and brain ALDH2 activity. The finding that blocking the brain ALDH2 (52%) by cyanamide can make a non‐aversive dose of AcH (25 mg/kg) aversive to UChA and UChB rats at blood AcH levels comparable to those induced by a non‐aversive dose of AcH (100 mg/kg) in control UChB rats indicates that the line difference in AcH aversion is associated more with brain ALDH2 activity than with liver ALDH2 activity.
Open field activity and EtOH activation of ?‐PKC null mutants
Authors: Hix DM , Bowers BJ , Miyamoto JH , Wehner JM
Published: January 2004

Null mutants of the neural‐specific γ‐isotype of protein kinase C (γ‐PKC) have demonstrated differential responses to acute administration of ethanol in comparison with wild‐type animals. Previous studies have shown that the mutants are less sensitive to ethanol‐induced loss of righting response. Null mutants also consume more ethanol and exhibit less behavioral inhibition. In order to determine if these sensitivity differences extend to ethanol activation of locomotor activity in an open‐field arena, baseline activity and the effect of two low doses of ethanol were assessed in γ‐PKC null mutants and wild‐type littermates. Null mutants demonstrated higher levels of baseline activity than did their wild‐type counterparts. Further analysis revealed that a 1.0 g/kg dose of ethanol increased locomotor activity in males and females of both genotypes, whereas only null mutant males were activated by a 1.25 g/kg ethanol dose. The current study demonstrates that male γ‐PKC null mutants exhibit increased sensitivity to activating doses of ethanol in contrast to previous findings of decreased sensitivity to higher, depressive doses. This reflects the pleiotropic effects of the γ‐PKC null mutation on the behavioral effects of ethanol.
Craving for cigarettes among low and high dependent smokers: impact of norharman
Authors: van den Eijnden Regina , Spijkerman Renske , Fekkes Durk
Published: January 2004

Besides nicotine, other chemicals in tobacco smoke, such as norharman, may contribute to the addictive properties of cigarettes. More specifically, elevated blood plasma levels of norharman may reduce feelings of craving among tobacco‐dependent individuals. To test this hypothesis, plasma concentrations of norharman were measured in 38 male smokers (at least 15 cigarettes per day) at three time‐points on 3 different days spread over a 4‐month period. The first measurement (T0) was conducted in the morning at 8.30 a.m., after 12 hours of smoking abstinence. The T1 and T2 measurements were conducted at 13.00 p.m. and 16.30 p.m., during a period of ad libitum smoking (after the T0 measurement, participants were not restricted in their smoking behaviour). At each of the nine time‐points, craving was assessed by means of a shortened version of the Questionnaire of Smoking Urges. The Fagerström Test of Nicotine Dependence was used to obtain an indication of nicotine dependence. The results showed that, after a period of smoking abstinence, craving was stronger in those with a high tobacco dependence than in those with a low tobacco dependence. After resumption of smoking, craving declined to a similar low level in both low and high dependent smokers. Measurements during periods of ad libitum smoking indicate that plasma levels of norharman are related negatively to craving among low nicotine‐dependent smokers, but not among high dependent smokers.
P‐glycoprotein modulation by the designer drugs methylenedioxymethamphetamine, methylenedioxyethylamphetamine and paramethoxyamphetamine
Authors: Ketabi‐Kiyanvash Nahal , Weiss Johanna , Haefeli Walter Emil , Mikus Gerd
Published: January 2004

There are increasing numbers of deaths related to taking MDMA, MDE and PMA reported where the deceased typically took several different drugs with these compounds. Hence, mutual modulation of the pharmacokinetics in drug combinations with “ecstasy” might be a risk factor for “ecstasy”‐related morbidity. Regarding potential drug‐drug interactions, there are no data evaluating a possible contribution of the multidrug resistance transporter P‐glycoprotein (Pgp) in contrast to the cytochrome P450 enzyme system. Therefore, individual “ecstasy” compounds have been tested for their ability to interact with Pgp using a fluorometric calcein assay as a model for Pgp inhibition in porcine kidney epithelial cells with overexpression of human Pgp (L‐MDR1). All three compounds increased calcein retention in L‐MDR1 cells in a concentration‐dependent manner, with MDE being the most potent and MDMA the weakest Pgp inhibitor. The effective concentrations were 1–3 orders of magnitude higher than plasma concentrations observed in vivo, suggesting that these compounds are only weak inhibitors of Pgp, which is unlikely to influence the access of other compounds to the brain. However, it cannot be excluded that co‐administration of Pgp inhibitors such as ritonavir or paroxetine could increase MDMA, MDE and PMA bioavailability and also enhance brain entry leading to severe side effects.
Age‐ and sex‐related differences in alcohol and nicotine effects in C57BL/6J mice
Authors: Lopez Marcelo , Simpson Damon , White Nancy , Randall Carrie
Published: January 2004

The present studies were aimed to identify possible age‐ and/or sex‐related differences in the effects of alcohol and nicotine. Study 1 examined age‐related differences in alcohol and nicotine effects. Adolescent and adult C57BL/6J male mice were injected with alcohol or nicotine. Results indicated that alcohol and nicotine induced hypothermia and reduced locomotor activity in both adolescent and adult mice. In both dependent variables, adults were more affected than adolescents that received the same alcohol or nicotine dose. Study 2 examined possible sex‐related differences in the effects of these drugs. Results replicated the aged‐related differences revealed in Study 1 after alcohol or nicotine administration in male mice. No sex‐related differences were observed in alcohol effects. However, young animals of both sexes and adult females appeared to be more resistant to nicotine effects. In both studies, blood alcohol concentrations and cotinine plasma concentrations were assessed. These results suggest that young C57BL/6J mice are more resistant to both alcohol and nicotine effects. In addition, adult females may be more resistant to acute nicotine effects on temperature and locomotion.