bluuebunny/crossref_metadata_2025 huggingface dataset:
Electron‐Transfer Chemistry of the Iron–Molybdenum Cofactor of Nitrogenase: Delocalized and Localized Reduced States of FeMoco which Allow Binding of Carbon Monoxide to Iron and Molybdenum
Authors: Pickett Christopher J. , Vincent Kylie A. , Ibrahim Saad K. , Gormal Carol A. , Smith Barry E. , Best Stephen P.
Published: December 2002

The electron‐transfer chemistry of the isolated iron–molybdenum cofactor of nitrogenase (FeMoco) has been studied by electrochemical and spectroelectrochemical methods. Two interconverting forms of the cofactor arise from a redox‐linked ligand isomerism at the terminal iron atom; this is attributed to rotamerism of an anionic N‐methyl formamide ligand bound at this site. FeMoco in its EPR‐silent oxidised state is shown to undergo three successive one‐electron transfer steps. We argue that the first and second redox processes are associated with electron‐transfer delocalised over the iron–sulfur core of the cofactor, whilst the third irreversible process is localised on molybdenum. This is strongly reinforced by spectroelectrochemical studies under 12CO and 13CO which reveal two independent carbon monoxide binding sites that are specifically associated with the second (iron core) and third (molybdenum) electron‐transfer processes and which give rise to terminal ν(12CO) bands at 1885 and 1920 cm−1 respectively. Moreover, in parallel with earlier studies on the enzyme system, it is shown that at low CO concentration, carbon monoxide binds to the cofactor in bridging modes, with ν(CO) bands at 1835 and 1808 cm−1 that are interconverted by single‐electron transfer. Importantly we show that the contentious overall 2e difference in the assignment of the metal oxidation levels in the resting state of the enzyme‐bound cofactor, arising from analysis of 57Fe ENDOR and Mössbauer data, can be resolved in the light of the electron‐transfer chemistry of the isolated cofactor described herein.
The Final Steps of the Oppolzer Cyclization: Mechanism of the Insertion of Alkenes into Allylpalladium(II) Complexes
Authors: Cárdenas Diego J. , Alcamí Manuel , Cossío Fernando , Méndez María , Echavarren Antonio M.
Published: December 2002

We report here the results of a computational study on the the mechanism of the Oppolzer cyclization. These results lead us to conclude that the insertion of olefins in Pd–allyl complexes probably takes place directly from theη3‐allyl species. The presence of a phosphane ligand in the reagents plays the role of enhancing the electron density on the Pd atom; this makes the alkene moiety more reactive towards insertion by back‐donation from the metal. The results also indicate that the configuration of the new stereogenic centers is fixed in the insertion of the alkene into the (η3‐allyl)palladium species.
Effects of controlled pH on organic and inorganic composition in haemolymph, epidermal tissue and cuticle of mud crab Scylla serrata
Authors: Pratoomchat Boonyarath , Sawangwong Pichan , Machado Jorge
Published: December 2002

Analysis of organic and inorganic compounds in plasma, epidermal tissue and cuticle were accomplished in the intermolt (C3 stage) of crab Scylla serrata incubated in different pH media. Significant changes with similar trends for protein, carbohydrates, glycosaminoglycans (GAG), sulphur, calcium, magnesium, potassium, phosphorus and copper in the plasma suggested higher dissolution in an acidic medium while the deposition increased in alkaline medium. Similar decreases in protein, carbohydrate and GAG in the epidermal compartment were observed from pH 4 to pH 12. However, significantly higher contents of sodium, chloride, potassium, phosphorus, magnesium, sulphur and copper were measured at pH 7.5 with a symmetrical decrease profile in both acidic and alkaline media, resulting from synergistic effects in the osmotic regulation. Clear changes in calcium concentrations were observed with a sharp increase from lower contents at pH 7.5 to higher at pH 12. In the cuticle, the acidic condition induced a significant dissolution of HCl‐protein, GAG, calcium and magnesium contents. On the other hand, the alkaline condition induced a significant decrease in carbohydrate, calcium, chloride, sulphur and potassium. A reduction trend is seen for NaOH and H2O‐protein contents in the cuticle. These observations suggest that GAG and HCl‐protein might constitute the most soluble fraction with high affinity for calcium binding and easily removed in acidic conditions. Additionally, it is possible to speculate that the carbohydrates associated with the NaOH and H2O‐proteins may form an interface between the soluble matrix fraction and the chitin framework. Sulphur groups seem to present a strong linkage role in this interface fraction, maybe only broken by a specific enzyme in extreme alkaline conditions with subsequent release of significant calcium from the shell. J. Exp. Zool.295A:47–56, 2003. © 2003 Wiley‐Liss, Inc.
Cyclin A2 Is differentially expressed during oocyte maturation between gynogenetic silver crucian carp and gonochoristic color crucian carp
Authors: Xie Jing , Wen Jian‐Jun , Yang Zhong‐An , Wang Hong‐Ying , Gui Jian‐Fang
Published: December 2002

Silver crucian carp (Carassius auratus gibelio) is a unique gynogenetic fish. Because of its specific genetic background and reproduction mode, it is an intriguing model system for understanding regulatory mechanism of oocyte maturation division. It keeps its chromosomal integrity by inhibiting the first meiotic division (no extrusion of the first pole body). The spindle behavior during oocyte maturation is significantly different from that in gonochoristic fish. The chromosomes are first arranged in a tripolar spindle, and then they turn around and are reunited mutually to form a normal bipolar spindle. A new member of the fish A‐type cyclin gene, cyclin A2, has been isolated by suppression of subtractive hybridization on the basis of its differential transcription in fully‐grown oocytes between the gynogenetic silver crucian carp and gonochoristic color crucian carp. There are 18 differing amino acids in the total 428 residues of cyclin A2 between the two forms of crucian carps. In addition, cDNAs of cyclin Al and cyclin B have also been cloned from them. Thus two members of A‐type cyclins, cyclin Al and cyclin A2, are demonstrated to exist in fish, just as in frog, humans, and mouse. Northern blotting reveals that cyclin A2 mRNA is more than 20‐fold and cyclin A1 mRNA is about 2‐fold in fully grown oocytes of gynogenetic silver crucian carp compared to gonochoristic color crucian carp. However, cyclin B does not show such a difference between them. Western blot analysis also shows that the cyclin A2 protein stockpiled in fully grown oocytes of gynogenetic crucian carp is much more abundant than in gonochoristic crucian carp. Moreover, two different cyclin A2 expression patterns during oocyte maturation have been revealed in the two closely related crucian carps. For color crucian carp, cyclin A2 protein is translated only after hormone stimulation. For silver crucian carp, cyclin A2 protein can be detected throughout the process of maturation division. The different expression of cyclin A2 may be a clue to understanding the special maturation division of gynogenetic silver crucian carp. J. Exp. Zool. 295A:1–16, 2003. © 2003 Wiley‐Liss, Inc.
Laser and Microwave Welding – The Applicability of New Process Principles
Authors: Potente Helmut , Karger Odo , Fiegler Georg
Published: December 2002

This article has been compiled on the basis of the many years' experience that has been acquired in the field of plastics welding by the Institute of Plastics Engineering (KTP) at the University of Paderborn. A brief report is given on the state of the art in laser and microwave welding technology. An overview is also included on the potential and limits of the use of laser and microwave welding in plastics processing. In the case of laser welding, a number of results achieved in welding of molded parts are presented that have been obtained in the course of extensive investigations. For microwave welding, a report is included on investigations that are currently running at the KTP. In addition to this, details are given on the basic suitability of laser and microwave welding for joining films and sheetings.

Configuration for the indirect microwave welding of panels, left: side view, right: cross‐section.

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Configuration for the indirect microwave welding of panels, left: side view, right: cross‐section.
An Approach to Calculating Wear on Annular Non‐Return Valves
Authors: Potente Helmut , Többen Wilhelm H. , Kaiser Elmar
Published: December 2002

The serviceability of non‐return valves has a major influence on the productivity of the injection molding process. During a meeting of experts held at our Institute, it was seen that closing behavior and wear are the key problems encountered in practice. The conducted investigations to tackle these questions have shown that both an improved closing behavior and a lower level of wear can be achieved by reducing the inside radius of the locking ring.

Pressure profile over the length of a non‐return valve (n = 0.4; ${\rm \dot V}$ = 25 000 mm3/s).

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Pressure profile over the length of a non‐return valve (n = 0.4; ${\rm \dot V}$ = 25 000 mm3/s).
Process Description for the Extrusion of Rubber Compounds – Development and Evaluation of a Screw Design Software
Authors: Limper Andreas , Schramm Dominik
Published: December 2002

The development of a mathematical model to be used in a simulation software for the description of rubber extrusion operating points is presented. A discrete model for the flow has been introduced, which considers the flow in the main direction and in the cross section of the screw channel. Moreover the flow model is connected with a discrete model for the computation of the temperature within the screw channel, an FDM approach has been used here. The combination permits the non‐isothermal flow simulation along extruder screws. Beside the isothermal and non‐isothermal option the simulation software, obtained on the basis of the models described, allows a multi‐variation of parameters as well. It is shown how such a variation mode can be used within a screw geometry optimization process and a short comparison of simulated and experimental data for the optimized concept is given. Further examples of comparison simulation/experiment are demonstrating that results can prone to error. The occuring lack of the model is most likely linked to an insufficient description of the rheology of rubber compounds. Further imperfection discussed are the processes within the feeding section. For example feed rolls and grooved barrels are often installed and effective for the process but not considered within theoretical models.

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Immunoglobulins against gp273, the ligand for sperm–egg interaction in the mollusc bivalve Unio elongatulus, are directed against charged O‐linked oligosaccharide chains bearing a Lewis‐like structure and interact with epitopes of the human zona pellucida
Authors: Focarelli Riccardo , Capone Antonietta , Ermini Leonardo , Del Buono Francesca , Battista La Sala Giovanni , Balasini Marcella , Rosati Floriana
Published: December 2002

In oocytes of the mollusc bivalve Unio elongatulus, gp273 is the ligand molecule for sperm–egg interaction and binding is mediated by its O‐glycans. A serum raised against this protein enabled its localization in the crater region, the area of the vitelline coat where sperm recognition occurs, and showed that after cyanogen bromide fragmentation, the anti‐gp273 epitope(s) was retained by a peptide where the O‐glycans are localized. In this article, we utilized purified anti‐gp273 immunoglobulins to characterize the corresponding epitope by: (i) immunoblotting analysis of the protein after removal of O‐ and N‐glycans; (ii) solid phase binding analysis of anti‐gp273 IgG to gp273 N‐ and O‐glycans; and (iii) binding analysis of the same antibody to commercially available oligosaccharides. The results showed that the epitope consists of O‐glycans and contains a Lewis‐like structure with fucose as determinant. Anti‐gp273 IgG were then used to investigate human zona pellucida by immunoelectronmicroscopy and immunoblotting. Epitopes recognized by the antibody were demonstrated on the outer surface of the zona pellucida and shown to belong to a zona pellucida protein having electrophoretic mobility similar to human ZP3. Since human sperm specifically bind to gp273, and anti‐gp273 interferes with this binding a functional role for these epitopes is suggested. Mol. Reprod. Dev. 64: 226–234, 2003. © 2003 Wiley‐Liss, Inc.
Changes of messenger RNAs encoding vascular endothelial growth factor and its receptors during the development and maintenance of caprine corpora lutea
Authors: Kawate Noritoshi , Tsuji Makoto , Tamada Hiromichi , Inaba Toshio , Sawada Tsutomu
Published: December 2002

The present study was conducted to examine changes of mRNAs encoding vascular endothelial growth factor (VEGF) and its receptors (KDR/Flk‐1 and Flt‐1), and CD34, which is known to be a specific marker for endothelial cells, during the development and maintenance of the caprine corpora lutea (CL). Effects of a potent GnRH antagonist (GA), which was previously shown to suppress release of luteinizing hormone (LH), on expressions of those mRNAs during the CL development were also investigated. Goats were divided into control (n = 12) and GA‐treated groups (n = 6). The goats were treated with saline or GA (50 μg/kg, sc) on days 0 (day of ovulation), 4, and 8 (control only), and CL collected on a subset of goats (n = 3 for each day) on days 0 (no saline), 4, 8, or 14 (control only). Ribonuclease protection assay was performed to quantitate the mRNAs in the CL using specific cRNA probes generated by RT‐PCR and in vitro transcription. Level of CD34 mRNA significantly increased from day 0 to 8 (CL development) in the control group (P < 0.05). Long and short forms were detected in the caprine CL by RT‐PCR for VEGF mRNA and analyses of their sequences showed that they correspond to mRNAs encoding VEGF165 and VEGF121, respectively. Level of VEGF165 mRNA significantly increased from day 4 to 8 and day 8 to 14 (CL maintenance) in the control group (P < 0.05) while VEGF121 mRNA did not change during the whole period. Level of KDR/Flk‐1 mRNA significantly increased from day 0 to 8 (P < 0.05) while Flt‐1 mRNA significantly increased from day 8 to 14 (P < 0.005) in the control group. In the GA‐treated group, levels of all of the mRNAs did not alter remarkably as compared with those in the control group. These results suggest that rise of KDR/Flk‐1 and VEGF165 mRNAs during the caprine CL development may be associated with enhanced angiogenesis and that increment of VEGF165 and Flt‐1 mRNAs during the CL maintenance may play nonangiogenic roles. The present study also indicates that the changes of VEGF165 and KDR/Flk‐1 mRNAs during the CL development are probably not regulated by LH. Mol. Reprod. Dev. 64: 166–171, 2003. © 2003 Wiley‐Liss, Inc.
Resumption of metabolic activity of vitrified/warmed ovine embryos
Authors: Leoni Giovanni , Berlinguer Fiammetta , Rosati Irma , Bogliolo Luisa , Ledda Sergio , Naitana Salvatore
Published: December 2002

To evaluate resumption of metabolic activity of vitrified ovine embryos during a short time immediately after warming, blastocysts collected from superovulated Sarda ewes were incubated with 35S‐methionine. In vitrified/warmed embryo groups the protein secretion significantly (P < 0.05) increased from 0 to 24 hr of culture, reaching significantly (P < 0.01) higher activity at 18–24 hr and dropping to values similar to the control nonvitrified embryo group at 29–35 hr. Within the control group at 29–35 hr there was a significantly (P < 0.01) higher level of protein secretion compared to the other interval times. The electrophoretic pattern showed a 48–50 kDa secreted protein identified as urokinase‐type plasminogen activator (PA). The caseinolytic assay of PA activity showed a course similar to protein secretion in both vitrified and control groups. During 29–35 hr of culture, we did not observe any improvement in PA activity as seen for secreted proteins. At this time, we observed the secretion of a new 20 kDa protein that was not present in vitrified/warmed embryos. Analysis of BrDU incorporation in newly synthesised DNA showed a significant (P < 0.01) improvement in positive cell number from 3 to 9 hr after warming, reaching a value similar to that of the control group at 12 hr of culture. Our results suggest that vitrified/warmed embryos require 9–12 hr of culture to complete resumption of DNA synthesis and 29–35 hr to re‐acquire the full capacity of protein secretion but not the qualitative secretion pattern. Mol. Reprod. Dev. 64: 207–213, 2003. © 2003 Wiley‐Liss, Inc.
Evidence for the Hypothesis of Ignition of Propellants by Metallic Vapour Deposition
Authors: Taylor Michael J.
Published: December 2002

This paper examines the experimental evidence to support the hypothesis of ignition of energetic material by the process of metallic vapour deposition. The hypothesis has been presented previously, and this is the continuation of the work. The hypothesis has been developed at QinetiQ to explain certain measurements of incident radiative flux during electrothermal‐chemical (ETC) experimentation, which show no correlation with the ignition event. Indeed, measured levels of radiation have been so low that radiative energy transfer for ETC plasma ignition could be said to be negligible. Measurement of the thickness of a metal layer resulting from dropwise vapour condensation gives good correlation to the flux requirements for ignition.
Characterization of Aluminum Powders I. Parameters of Reactivity of Aluminum Powders
Authors: Ilyin Alexander , Gromov Alexander , An Vladimir , Faubert François , de Izarra Charles , Espagnacq André , Brunet Luc
Published: December 2002

For testing the determination of the reactivity of aluminum powders it is proposed to use the following parameters: temperature of the beginning of oxidation, maximal oxidation rate, degree of transformation (degree of oxidation) of aluminum, relative thermal effect. Parameters for an evaluation of the reactivity of powders were chosen following the analysis of results of a non‐isothermal oxidation of powders of different grain size under conditions of programmed heating (the oxidizer being air). According to the proposed method of testing, the sample of ultrafine powder UFAP‐4 produced by the electrical explosion of wires has the highest reactivity among the studied powders.
Electronic properties of Si/SiGe ultrathin quantum well superlattices
Authors: Rached D. , Benkhettou N. , Sekkal N.
Published: December 2002

Using the self‐consistent and perturbative method of Jaros and the full potential linear muffin tin orbitals (FP‐LMTO) method coupled to a plane wave (PLW) basis in the interstitial regions, we calculate the bandstructure of some ultrathin Sim/(SiGe)n quantum well superlattices, m and n being the numbers of atomic layers. The results show that in these systems the bandgap is indirect and that these superlattices have a type II potential configuration.
DX behaviour of Si donors in AlGaN alloys
Authors: Brandt Martin S. , Zeisel Roland , Gönnenwein Sebastian T. B. , Bayerl Martin W. , Stutzmann Martin
Published: December 2002

Recent experiments on the DX behaviour of Si in AlGaN alloys are reviewed. From persistent photoconductivity, light‐induced electron spin resonance, and thermal quenching experiments as well as from the thermal activation of the generation‐recombination noise, a quantitative configuration coordinate diagram is constructed for pure AlN and Al0.75Ga0.25N. The effects of DX centres on the properties of AlGaN alloys with lower Al concentration are discussed.
Resonant states in doped quantum wells
Authors: Blom A. , Odnoblyudov M.A. , Yassievich I.N. , Chao K.A.
Published: December 2002

Resonant states can have an important influence on the electronic transport, noise and optical properties of heterostructure devices. We have used a non‐variational method to study the resonant states formed by shallow donors inside and outside of quantum wells. The method allows us the evaluation of the position and the width (lifetime) of the resonant states and also of matrix elements such as optical transition probabilities. When the width is compared to results from the approach of resolvent operators, a quantitative difference is found, which we attribute to the neglected intraband scattering in the latter method. We also show how the impurity states, localized and resonant, evolve as the donor is moved into the quantum well from an originally infinite distance.
Optically pumped terahertz semiconductor bulk lasers
Authors: Pavlov S. G. , Hübers H.‐W. , Orlova E. E. , Zhukavin R. Kh. , Riemann H. , Nakata H. , Shastin V. N.
Published: December 2002

The principles of stimulated emission for the terahertz frequency range from shallow impurity centers in bulk semiconductors are discussed. Evidence of stimulated emission from group V donors embedded in silicon (P, Sb, Bi) as well as spontaneous emission from Li acceptor in monocrystalline ZnSe under excitation by CO2 laser radiation at low temperatures is demonstrated. The temporal behavior and the emission spectra of the lasers are presented.
THz lasing of SiGe/Si quantum‐well structures due to shallow acceptors
Authors: Kagan M. S. , Altukhov I. V. , Chirkova E. G. , Sinis V. P. , Troeger R. T. , Ray S. K. , Kolodzey J.
Published: December 2002

An intense THz emission was observed from strained SiGe/Si quantum‐well structures under strong pulsed electric field. The p‐type structures were MBE‐grown on n‐type Si substrates and δ‐doped with boron. Lines with wavelengths near 100 microns were observed in the emission spectrum. The modal structure in the spectrum gave evidence for the stimulated nature of the emission. The origin of the THz emission was attributed to intra‐centre optical transitions between resonant and localized boron levels.
Hydrogen as a shallow center in semiconductors and oxides
Authors: Van de Walle Chris G.
Published: December 2002

We describe the physics of interstitial hydrogen in semiconductors and oxides based on a first‐principles computational approach. In most semiconductors hydrogen acts as an amphoteric impurity, compensating the prevailing conductivity. In ZnO, however, hydrogen acts a shallow donor. We have developed a general model for the behavior of hydrogen in semiconductors and oxides, and confirmed its predictive nature in the case of InN and GaAsN alloys.
Nitrogen–hydrogen complexes in GaAs and GaAs1–xNx alloys
Authors: Kim Yong‐Sung , Chang K.J.
Published: December 2002

We investigate the atomic structure of various N–H complexes in GaAs and GaAs1–xNx alloys through first‐principles pseudopotential calculations within the local‐density‐functional approximation. For GaAs with low H concentrations, we suggest that nitrogen forms a N–H(BC) complex, where H is positioned at a bond‐center site between a substitutional N and one of the neighboring Ga atoms. For very high H concentrations, an optically inactive N–H2*(BC‐ABN) complex, which corresponds to a configuration of H2* in the vicinity of N, is suggested to be an energetically favorable structure. These atomic models explain many experimental features observed in GaAs and GaAs1–xNx alloys, which contain both N and H.
Donor centers in zinc germanium diphosphide produced by electron irradiation
Authors: Gehlhoff W. , Azamat D. , Hoffmann A.
Published: December 2002

The properties of defects in p‐type zinc germanium diphosphide (ZnGeP2) were studied by means of electron paramagnetic resonance (EPR) and photo‐EPR. Besides the well‐known three native defects (VZn, VP, GeZn) an S = 1/2 EPR spectrum is observed in electron‐irradiated ZnGeP2 with an isotropic g = 2.0123 and resolved hyperfine splitting from four equivalent I = 1/2 neighbors. This spectrum is caused by a new center generated by the electron‐irradiation and not by an existing center that is recharged as a result of the irradiation induced Fermi‐level shift. It is tentatively assigned to the isolated Ge vacancy. Observation of the photoinduced recharging processes demonstrates that the location of the level VGe3–/2– is at Eopt = (0.7 ± 0.06) eV. An annealing of the electron‐irradiated samples causes a reverse shift of the Fermi level in direction to its original position and is accompanied with a reduction of an isotropic unstructured line at g = 2.003 caused by the irradiation damage.
Coral mortality and recovery in response to increasing temperature in the southern Arabian Gulf
Authors: Sheppard Charles , Loughland Ronald
Published: December 2002

Analysis of a new data set for sea surface temperature shows that the seawater temperature rise in 1998 in the southern Arabian Gulf was the largest since 1870; it also showed that there is an underlying rising trend of sea surface temperature across the whole of the measured area spanning 5 degrees longitude and 3 degrees latitude. Over the last 50 years, sea surface temperature rise was about 0.2°C per decade, though this has accelerated to about 0.45°C per decade in the last 20 years. The pattern in temperature values in each 1 degree ‘cell’ are used to show that, at any one time, temperature rises towards the east of this area, which supports the concept of a general anti-clockwise circulation in the southeastern half of the Arabian Gulf. Spatial and temporal patterns in sea surface temperature rises also show that the mean temperature field at any location is similar to that which existed in the one degree cell immediately to its east approximately 30 years earlier.

Coral cover in shallow water (<3 m depth) was <1 percent immediately following the 1998 event, due to near total mortality of vast areas of shallow Acropora (stagshorn) corals. Deeper than 3 m there was increasing survival of the large Porites (boulder) corals, survival increasing with depth. Coral survival improved towards the east, though overall, less than twenty coral species were found altogether. Juvenile recruitment also increased towards the east, and at any one site, recruitment increased with increasing depth. The identity of new juveniles was mainly faviid corals, not the Acropora or Porites which dominated these reefs before the 1998 event. This suggests that there may be a phase shift to a different stable state in terms of coral communities. We also speculate that, because the Arabian Gulf contains an extreme warm-tolerant subset of the Indian Ocean coral fauna, the changes seen in the Gulf may reflect future patterns across a greater part of the Indian Ocean.
Analysis of the Compartmentation of Glycolytic Intermediates, Nucleotides, Sugars, Organic Acids, Amino Acids, and Sugar Alcohols in Potato Tubers Using a Nonaqueous Fractionation Method
Authors: Farré Eva M. , Tiessen Axel , Roessner Ute , Geigenberger Peter , Trethewey Richard N. , Willmitzer Lothar
Published: December 2002

The compartmentation of metabolism in heterotrophic plant tissues is poorly understood due to the lack of data on metabolite distributions and fluxes between subcellular organelles. The main reason for this is the lack of suitable experimental methods with which intracellular metabolism can be measured. Here, we describe a nonaqueous fractionation method that allows the subcellular distributions of metabolites in developing potato (Solanum tuberosum L. cv Desiree) tubers to be calculated. In addition, we have coupled this fractionation method to a recently described gas chromatography-mass spectrometry procedure that allows the measurement of a wide range of small metabolites. To calculate the subcellular metabolite concentrations, we have analyzed organelle volumes in growing potato tubers using electron microscopy. The relative volume distributions in tubers are very similar to the ones for source leaves. More than 60% of most sugars, sugar alcohols, organic acids, and amino acids were found in the vacuole, although the concentrations of these metabolites is often higher in the cytosol. Significant amounts of the substrates for starch biosynthesis, hexose phosphates, and ATP were found in the plastid. However, pyrophosphate was located almost exclusively in the cytosol. Calculation of the mass action ratios of sucrose synthase, UDP-glucose pyrophosphorylase, phosphoglucosisomerase, and phosphoglucomutase indicate that these enzymes are close to equilibrium in developing potato tubers. However, due to the low plastidic pyrophosphate concentration, the reaction catalyzed by ADP-glucose pyrophosphorylase was estimated to be far removed from equilibrium.
N-terminal residues in murine P-selectin glycoprotein ligand-1 required for binding to murine P-selectin
Authors: Xia Lijun , Ramachandran Vishwanath , McDaniel J. Michael , Nguyen Kiem N. , Cummings Richard D. , McEver Rodger P.
Published: December 2002

P-selectin binds to the N-terminal region of human P-selectin glycoprotein ligand-1 (PSGL-1). For optimal binding, this region requires sulfation on 3 tyrosines and specific core-2O-glycosylation on a threonine. P-selectin is also thought to bind to the N terminus of murine PSGL-1, although it has a very different amino acid sequence than human PSGL-1. Murine PSGL-1 has potential sites for sulfation at Tyr13 and Tyr15 and for O-glycosylation at Thr14 and Thr17. We expressed murine PSGL-1 or constructs with substitutions of these residues in transfected Chinese hamster ovary cells that coexpressed the glycosyltransferases required for binding to P-selectin. The cells were assayed for binding to fluid-phase P-selectin and for tethering and rolling on P-selectin under flow. In both assays, substitution of Tyr13 or Thr17 markedly diminished, but did not eliminate, binding to P-selectin. In contrast, substitution of Tyr15 or Thr14 did not affect binding. Substitution of all 4 residues eliminated binding. Treatment of cells with chlorate, an inhibitor of sulfation, markedly reduced binding of wild-type PSGL-1 to P-selectin but did not further decrease binding of PSGL-1 with substitutions of both tyrosines. These data suggest that sulfation of Tyr13 andO-glycosylation of Thr17 are necessary for murine PSGL-1 to bind optimally to P-selectin. Because it uses only one tyrosine, murine PSGL-1 may rely more on other peptide components andO-glycosylation to bind to P-selectin than does human PSGL-1.
Dose escalation of imatinib mesylate can overcome resistance to standard-dose therapy in patients with chronic myelogenous leukemia
Authors: Kantarjian Hagop M. , Talpaz Moshe , O'Brien Susan , Giles Francis , Garcia-Manero Guillermo , Faderl Stefan , Thomas Deborah , Shan Jianqin , Rios Mary Beth , Cortes Jorge
Published: December 2002

We investigated whether increasing the dose of imatinib mesylate might overcome drug resistance in patients with Philadelphia chromosome–positive (Ph+) chronic myelogenous leukemia (CML) whose disease manifests relapse or refractoriness to therapy. Fifty-four patients with Ph+ CML in chronic phase and with hematologic or cytogenetic resistance or relapse on imatinib mesylate therapy at 400 mg orally daily were treated with a higher dose of 400 mg orally twice daily (800 mg daily, 47 patients; or 600 mg daily increased from 300 mg daily, 7 patients). Among 20 patients treated for hematologic resistance or relapse, 13 (65%) achieved a complete (n = 9) or partial (n = 4) hematologic response, but only 1 had a cytogenetic partial response (Ph reduction from 100% to 10%) and 1 had a minor response (Ph reduction from 100% to 50%). Among 34 patients treated for cytogenetic resistance or relapse, 19 (56%) achieved a complete (n = 6) or partial (n = 7) cytogenetic response. We conclude that higher doses of imatinib mesylate may overcome disease-poor response to conventional doses and that this approach deserves further evaluation as frontline therapy for newly diagnosed CML.
Rituximab therapy for CNS lymphomas: targeting the leptomeningeal compartment
Authors: Rubenstein James L. , Combs Dan , Rosenberg Jay , Levy Arthur , McDermott Michael , Damon Lloyd , Ignoffo Robert , Aldape Kenneth , Shen Arthur , Lee Dana , Grillo-Lopez Antonio , Shuman Marc A.
Published: December 2002

Most lymphomas that involve the central nervous system are B-cell neoplasms that express the cell surface molecule CD20. After intravenous administration, rituximab can be reproducibly measured in the cerebrospinal fluid (CSF) in patients with primary central nervous system lymphoma; however, the CSF levels of rituximab are approximately 0.1% of serum levels associated with therapeutic activity in patients with systemic non-Hodgkin lymphoma. Because lymphomatous meningitis is a frequent complication of non-Hodgkin lymphoma, we have conducted an analysis of the safety and pharmacokinetics of direct intrathecal administration of rituximab using cynomolgus monkeys. No significant acute or delayed toxicity, neurologic or otherwise, was detected. Pharmacokinetic analysis suggests that drug clearance from the CSF is biphasic, with a terminal half-life of 4.96 hours. A phase 1 study to investigate the safety and pharmacokinetics of intrathecal rituximab in patients with recurrent lymphomatous meningitis will be implemented based on these findings.
Genetic analysis of de novo CD5+ diffuse large B-cell lymphomas suggests an origin from a somatically mutated CD5+ progenitor B cell
Authors: Katzenberger Tiemo , Lohr Andreas , Schwarz Stephan , Dreyling Martin , Schoof Julia , Nickenig Christina , Stilgenbauer Stephan , Kalla Jörg , Ott M. Michaela , Müller-Hermelink Hans Konrad , Ott German
Published: December 2002

CD5+ diffuse large B-cell lymphomas (DLBLs) have recently been described as a particular subgroup of DLBLs. Classical banding and interphase cytogenetic analyses targeting ATM, TP53, and P16INK4a genes and theD13S25 locus from 13 CD5+ DLBLs were compared with 55 CD5− DLBLs. Additionally, analysis of somatic mutations of the immunoglobulin heavy chain variable region (IgVH) genes were performed in CD5+ DLBLs. CD5+DLBLs were somatically mutated (7 of 8 cases) and were negative for t(11;14)(q13;q32) and t(14;18)(q32;q21), whereas t(3;14)(q27;q32) was found in only one tumor. Trisomy 3 and gains on chromosomes 16/16p and 18/18q were significantly overrepresented in CD5+DLBLs. No ATM deletions were detected. The prevalence of deletions at the D13S25 locus was significantly higher in CD5+ DLBLs (4 of 12 [33%]) compared with CD5− DLBLs (4 of 42 [10%]), as were p16INK4a deletions (33% versus 8%). On the basis of these findings, CD5+ DLBLs are likely to arise from the same progenitor cell as the mutated variant of CD5+ lymphocytic lymphoma/B-cell chronic lymphocytic leukemia (B-CLL).
Glycosylation-dependent inhibition of cutaneous lymphocyte–associated antigen expression: implications in modulating lymphocyte migration to skin
Authors: Dimitroff Charles J. , Bernacki Ralph J. , Sackstein Robert
Published: December 2002

Constitutive E-selectin expression on dermal microvascular endothelial cells plays a critical role in mediating rolling adhesive interactions of human skin–homing T cells and in pathologic accumulation of lymphocytes in skin. The major E-selectin ligand on human skin–homing T cells is cutaneous lymphocyte–associated antigen (CLA), a specialized glycoform of P-selectin glycoprotein ligand-1 (PSGL-1) defined by monoclonal antibody HECA-452. Since HECA-452 reactivity, and not PSGL-1 polypeptide itself, confers the specificity of human T cells to enter dermal tissue, inhibition of HECA-452 expression is a potential strategy for modulating lymphocyte migration to skin. In this study, we examined the efficacy of several well-characterized metabolic inhibitors of glycosylation and of a novel fluorinated analog of N-acetylglucosamine (2-acetamido-1,3,6-tri-O-acetyl-4-deoxy-4-fluoro-D-glucopyranose [4-F-GlcNAc]) to alter HECA-452 expression on human CLA+ T cells and prevent cell tethering and rolling on selectins under shear stress. At concentrations that did not affect PSGL-1 expression, we found that swainsonine (inhibitor of complex-typeN-glycan synthesis) had no effect on HECA-452 expression or selectin ligand activity, whereas benzyl-O-N-acetylgalactosamide (BAG; inhibitor of O-glycan biosynthesis) ablated HECA-452 expression on PSGL-1 and significantly lowered selectin ligand activity. We found that 4-F-GlcNAc (putative inhibitor of poly-N-acetyllactosamine biosynthesis) was more potent than BAG at lowering HECA-452 expression and selectin binding. In addition, we show that 4-F-GlcNAc was directly incorporated into native CLA expressed on T cells, indicating direct inhibition on poly-N-acetyllactosamine elongation and selectin-binding determinants on PSGL-1 O-glycans. These observations establish a potential treatment approach for targeting pathologic lymphocyte trafficking to skin and indicate that 4-F-GlcNAc may be a promising agent for treatment of dermal tropism associated with malignancies and inflammatory disorders.
Fibrates down-regulate IL-1–stimulated C-reactive protein gene expression in hepatocytes by reducing nuclear p50-NFκB–C/EBP-β complex formation
Authors: Kleemann Robert , Gervois Philippe P. , Verschuren Lars , Staels Bart , Princen Hans M. G. , Kooistra Teake
Published: December 2002

C-reactive protein (CRP) is a major acute-phase protein in humans. Elevated plasma CRP levels are a risk factor for cardiovascular disease. CRP is predominantly expressed in hepatocytes and is induced by interleukin-1 (IL-1) and IL-6 under inflammatory situations, such as the acute phase. Fibrates are hypolipidemic drugs that act through the nuclear receptor peroxisome proliferator-activated receptor-α (PPAR-α). Fibrates have been shown to reduce elevated CRP levels in humans, but the molecular mechanism is unknown. In this study, we demonstrate that different PPAR-α activators suppress IL-1–induced, but not IL-6–induced, expression of CRP in primary human hepatocytes and HuH7 hepatoma cells. Induction of CRP expression by IL-1 occurs at the transcriptional level. Site-directed mutagenesis experiments show that IL-1 induces CRP expression through 2 overlapping response elements, the binding sites for CCAAT-box/enhancer–binding protein-β (C/EBP-β) and p50-nuclear factor-κB (p50-NFκB). Cotransfection of C/EBP-β and p50-NFκB enhances CRP promoter activity, and coimmunoprecipitation experiments indicate that the increase in CRP promoter activity by IL-1 is related to the generation and nuclear accumulation of C/EBP-β–p50-NFκB complexes. Interestingly, PPAR-α activators reduce the formation of nuclear C/EBP-β–p50-NFκB complexes, and thereby CRP promoter activity, by 2 mechanisms. First, PPAR-α increases IκB-α expression and thus prevents p50-NFκB translocation to the nucleus. Second, fibrates decrease hepatic C/EBP-β and p50-NFκB protein levels in mice in a PPAR-α–dependent way. Our findings identify C/EBP-β and p50-NFκB as novel targets for PPAR-α and provide a molecular explanation for the reduction of plasma CRP levels by fibrates.
Drug treatment of depression: reflections on the evidence
Authors: Anderson Ian M.
Published: December 2002

Guidelines are readily available for the treatment of depression, and more recent ones are explicitly evidence-based. Their core messages vary little but they tend to minimise uncertainties and gloss over difficult areas. This article examines three areas of uncertainty: the thresholds of severity and, for milder depression, the duration of illness for which antidepressants are more effective than placebo; the next step in drug treatment when a patient has failed to respond adequately to a first antidepressant; and how long continuing on antidepressants should be recommended in relation to individual patients' needs. It is concluded that the uncertainties in relation to treating individual patients are a combination of lack of evidence and individual patient factors but there is also an intrinsic uncertainty that will continue to require good clinical judgement.
Mental health of the ageing immigrant population
Authors: Livingston Gill , Sembhi Sati
Published: December 2002

About 6% of older people in the UK are immigrants. Concentrated in deprived inner-city areas, their numbers are rising rapidly, with the ageing of those arriving after the Second World War. Cultural, language and educational differences cause problems in studying this group's mental health. Idioms of distress may affect presentation, help-seeking behaviour and acceptability of treatment. Ethnic elders may be considered vulnerable to depression because of socio-economic deprivation, immigrant status and old age but studies are contradictory and may use inappropriate screening instruments. Relatively few consider immigrant status and dementia. Uncontrolled hypertension could relate to higher dementia rates in Black immigrants which are not reflected in the country of origin. No genetic risk has been found. There is potential for prevention in this population.
Training for approval under Section 12(2) of the Mental Health Act 1983
Authors: Brown Nicholas , Humphreys Martin
Published: December 2002

The history and meaning of doctors' approval by the Secretary of State under Section 12(2) of the Mental Health Act 1983 is discussed. The definition for approval is examined with relevant rulings on interpretation. Training requisites of such doctors are examined, outlining a framework of educational aims and objectives, with suggestions for delivery. The aims must include direct factual content and also the skills, values and attitudes required for humane and consistent practice. The particular needs of some specific groups and individuals are highlighted. The continual learning for updating skills and knowledge, including event-based learning, audit and reflection, is placed in the context of clinical governance wherein doctors must ensure that they continue to be ‘fit for purpose’. The case is made for ‘nationalisation’ of the syllabus and standards.
Theories of general personality and mental disorder
Authors: Duggan C. , Milton J. , Egan V. , McCarthy L. , Palmer B. , Lee A.
Published: December 2002

Background

A major short coming of current research into personality is its failure to explore the relationship between theories of general personality and mental disorder.

Aims

To provide preliminary data to address this deficit.

Method

In the first of two studies, we examined the relationship between the Neuroticism, Extraversion and Other – Five-Factor Inventory (NEO–FFI) and DSM personality disorders in a consecutive series of mentally disordered offenders. In the second, we sought to separate the personality dimension neuroticism from symptoms of depressive disorder in a sample of subjects with current depression.

Results

Factors from the NEO–FFI were associated with different personality disorders in a predictable manner (first study). It was possible to identify a component of neuroticism (i.e. ‘worry’) that could be separated from depressive symptoms (second study).

Conclusions

Theories of general personality theory can enlighten and refine descriptions of abnormal mental states by informing both their aetiology and their prognosis.
Rescue of arrested RNA polymerase II complexes
Authors: Svejstrup Jesper Q.
Published: December 2002

In the past few months, several discoveries relating to the mechanism underlying transcription-coupled DNA repair (TCR) have been reported. These results make it timely to propose a hypothesis for how eukaryotic cells might deal with arrested RNA polymerase II (Pol II) complexes. In this model, the transcription-repair coupling factor Cockayne Syndrome B (or the yeast equivalent Rad26) uses DNA translocase activity to remodel the Pol II-DNA interface, possibly to push the polymerase past the obstruction or to remove it from the DNA so that repair can take place if the obstacle is a DNA lesion. However, when this action is not possible and Pol II is left irreversibly trapped on DNA, the polymerase is instead ubiquitylated and eventually removed by proteolysis.
Resonant Tunneling Processes along Conjugated Molecular Wires: A Quantum‐Chemical Description
Authors: Karzazi Y. , Cornil J. , Brédas J.‐L.
Published: December 2002

Molecular electronics research is a very active area in the field of nanotechnology. It is now well established that individual or self‐assembled molecules can behave as nanoscopic switches in transistor and diode configurations. Molecular wires inserted into nanopores and contacted by two metallic electrodes can also be used as active elements for the fabrication of resonant tunneling diodes (RTDs). The RTD current/voltage (I/V) characteristics can display a negative differential resistance (NDR) behavior (i.e., a negative slope in the I/V curve) for reasons that are not yet fully understood. Here we describe a possible mechanism at the quantum‐chemical level that is based on conformational effects and accounts for the experimental observation of strong NDR signatures in substituted phenylene ethynylene oligomers. The occurrence of a peak current in the I/V curves is rationalized by analyzing the evolution of the one‐electron structure of the molecular wires upon application of a static electric field aligned along the molecular axis (the field simulates the driving voltage applied between the two electrodes in the RTD devices). The results of our calculations provide a general basis to develop strategies for the design of molecular wires displaying an NDR behavior.
Macroporous Silica From Solid‐Stabilized Emulsion Templates
Authors: Binks B.P.
Published: December 2002

Macroemulsions stabilized solely by nanoparticles of modified silica are used to prepare porous silica solid materials (see Figure), following slow evaporation of the two liquids. Both oil‐in‐water and water‐in‐oil emulsions can be employed, and the average pore size is close to the original emulsion drop diameter. Spherical or bicontinuous‐like pores may form, depending on the properties of the template emulsion.
ZnO Nanoneedles Grown Vertically on Si Substrates by Non‐Catalytic Vapor‐Phase Epitaxy
Authors: Park W.I. , Yi G.‐C. , Kim M. , Pennycook S.J.
Published: December 2002

Catalyst‐free metal–organic chemical vapor deposition (MOCVD) is used to prepare ZnO nanoneedles, grown vertically on Si substrates. Electron microscopy reveals that the nanoneedles are sharp, have uniform diameters, lengths, and densities, and high crystallinity. The photoluminescence spectrum displays a strong emission peak at 3.29 eV with a very weak deep‐level emission, indicating that the nanoneedles are of high optical quality.
3,4‐Ethylenedioxythiophene–Pyridine‐Based Polymers: Redox or n‐Type Electronic Conductivity?
Authors: DuBois C.J. , Reynolds J.R.
Published: December 2002

A family of polymers based on alternating bi‐EDOT and pyridine units is reported. Poly(BEDOT‐PyrPyr‐Ph2), with a bandgap of 1.2 eV, has four electrochemically accessible colors (dark gray, burgundy, lime green, and light gray) each corresponding to a distinct redox state. In‐situ conductance measurements illustrate high n‐type doping conductances only thirty times less than those of the p‐type doping conductances.
Bicontinuous Cubic Block Copolymer Photonic Crystals
Authors: Urbas A.M. , Maldovan M. , DeRege P. , Thomas E.L.
Published: December 2002

Three‐dimensional photonic crystals are fabricated from block copolymers, forming a double gyroid network structure. Further processing produces three‐dimensionally nanoporous, freestanding materials (see Figure), and allows dielectric enhancement and infiltration, which dramatically improve optical and material properties. These etched materials provide a path to highly effective photonic crystals via self‐assembly.
7‐Substituted‐[1, 4]dioxano[2, 3‐g]quinazolines as Inhibitors of Epidermal Growth Factor Receptor Kinase
Authors: Lee Jae Yeol , Park Yong Kyu , Seo Seon Hee , Yang Beom‐Seok , Park Hokoon , Lee Yong Sup
Published: December 2002

With the aim of developing inhibitors of EGFR tyrosine kinase, the 7‐methoxymethyl‐[1, 4]dioxano[2, 3‐g]quinazolines (3a—b) and 7‐mono‐ or di‐alkylaminomethyl‐[1, 4]dioxano[2, 3‐g]quinazolines (4a—i) were prepared and evaluated for the inhibition of EGFR tyrosine kinase and the growth inhibition of human tumor cell lines. Among them, compounds 4d and 4h showed potencies against both EGFR tyrosine and the A431 cell line similar to that of PD153035 with greater aqueous solubilities of their HCl salts.