bluuebunny/crossref_metadata_2025 huggingface dataset:
Chemical bonding in crystalline silver halides: Wannier‐type atomic functions approach
Authors: Evarestov R. A. , Smirnov V. P. , Usvyat D. E.
Published: November 2003

A method for chemical bonding analysis based on the minimal basis of Wannier‐type atomic orbitals (WTAOs) is suggested. WTAOS are formed by the Bloch states of upper valence and lower conduction bands. They are centered on atoms and have the symmetry of atomic‐like functions. A variational procedure is formulated for WTAOs generation. This procedure is equally applied to Bloch states in a basis of LCAO, plane waves, or any other set of functions. The proposed approach is used in analysis of the local properties of the electronic structure (atomic charges, bond orders, covalencies, and valencies) in silver halides AgF, AgCl, and AgBr obtained by the Hartree–Fock LCAO method. The advantages of WTAOs population analysis in comparison to the traditional LCAO Mulliken and Löwdin ones are discussed. © 2003 Wiley Periodicals, Inc. Int J Quantum Chem, 2004
Single and regular hydrogenation and oxidation of carbon nanotubes: MNDO calculations
Authors: Zaporotskova I. V. , Lebedev N. G. , Chernozatonskii L. A.
Published: November 2003

Calculations of electron energetic characteristics of atomic hydrogen adsorption processes on internal and external surfaces of single‐walled carbon nanotubes (tubulenes) of (6,6) “armchair” type having cylindrical symmetry have been carried out. This article reports also on the results of calculations of the atomic adsorption of oxygen on the surface of armchair and zigzag single‐walled carbon nanotubes. Ionic‐embedded covalent‐cyclic cluster (IECCC) and molecular cluster models within the framework of semiempirical quantum chemical scheme MNDO well shown in the theoretical researches of electronic molecular and periodic solid‐state structures have been used. The electronic and energy characteristics of the oxidation processes are analyzed, and the most energetically favorable oxide structure of the (6,6) nanotube is determined. It is found that narrow‐gap nanotubes show a tendency to metallic behavior as their surface is saturated with oxygen atoms. © 2003 Wiley Periodicals, Inc. Int J Quantum Chem, 2004
Orbital‐stoichiometric cluster model of carbon nanotube generation on quantum dots of diamond surface
Authors: Lebedev N. G. , Ponomareva I. V. , Chernozatonskii L. A.
Published: November 2003

The orbital‐stoichiometric cluster (OSC) model in the framework of quantum chemical MNDO scheme has been applied to simulate the diamond nanocluster to study carbon nanotube generation process on the diamond (111) surface. In this model the cluster orbital basis includes all internal atom orbits. The bordering atoms bring in the base only sp3‐hybrid orbits directed inside of the cluster. Some ways of nanotube growth have been considered: by absorption of monomers, dimmers, and trimmers of carbon. The comparison of the received characteristics of processes, in particular adsorption energy, has shown that the most favorable process is carbon monomer sorption on a pure diamond (111) surface. Processes of nanotube origin on surface quantum dots, which have been simulated by adsorbed Li, Na, K, Be, and H atoms, have shown high efficiency of nanotube growth: All of them proceed without energy barriers. © 2003 Wiley Periodicals, Inc. Int J Quantum Chem, 2004
Liability of foreignness in global competition? Financial service affiliates in the city of London
Authors: Nachum Lilach
Published: November 2003

This study was inspired by the observation that foreign financial service firms operating in the City of London do not suffer the liability of foreignness to the extent suggested by theory. To examine the reasons for this departure from theory, the study advances a theoretical framework that distinguishes between three types of advantages that together account for the competitive performance of MNEs relative to that of indigenous firms. Empirical analyses of a sample of 296 foreign financial service firms in the City of London show that in this particular context major sources of competitive performance are the firm‐specific advantages and the advantages of multinationality, where British firms may not necessarily possess an advantage over foreign firms. An examination of the validity of the findings, in order to assess the extent to which this situation is unique to the City of London or rather signifies a more general trend that requires theoretical modifications and extensions, is emphasized as a major task for future research. Copyright © 2003 John Wiley & Sons, Ltd.
Knowledge‐based resources, entrepreneurial orientation, and the performance of small and medium‐sized businesses
Authors: Wiklund Johan , Shepherd DEAN
Published: November 2003

While theory suggests that management has discretion in manipulating resources in order to build competitive advantage, resource‐based research has focused on the characteristics of resources, paying less attention to the relationship between those resources and the way firms are organized. In explaining performance, entrepreneurship scholars have focused on a firm's entrepreneurial strategic orientation (EO), leaving its interrelationship with internal characteristics aside. We argue that EO captures an important aspect of the way a firm is organized. Our findings suggest that knowledge‐based resources (applicable to discovery and exploitation of opportunities) are positively related to firm performance and that EO enhances this relationship. Copyright © 2003 John Wiley & Sons, Ltd.
Connected in Seattle? An exploratory study of student perceptions of discipline and attachments to teachers
Authors: Wald Johanna , Kurlaender Michal
Published: November 2003

How do students' perceptions about their treatment in school differ along racial and gender lines?
Deconstructing the pipeline: Using efficacy, effectiveness, and cost‐benefit data to reduce minority youth incarceration
Authors: Osher David M. , Quinn Mary Magee , Poirier Jeffrey M. , Rutherford Robert B.
Published: November 2003

Investing in effective prevention and early intervention programs will reduce human costs of victimization and also save tax dollars in the short and long terms.
Are prions misfolded molecular chaperones?
Authors: Liautard Jean-Pierre
Published: November 2003

A theory has been developed that could explain prion infection. Prions could be molecular chaperones that are required for their own assembly. The theory has been deduced from an analysis of protein folding and consequences explored by computer simulations. Thermo‐kinetic analysis of protein folding shows that a misfolded chaperone gives rise to new misfolded chaperones. Consequently such a protein could behave as a new kind of informative molecule and replicate misfolding according to a process similar to infection. A quantitative model has been derived from this hypothesis that displays the characteristics of prion infections. This hypothesis satisfactorily explains the three manifestations infection, familial and sporadic — that are the characteristics features of all prion diseases.
Fatty acid circuit as a physiological mechanism of uncoupling of oxidative phosphorylation
Authors: Skulachev Vladimir P.
Published: November 2003

Free fatty acids, natural uncouplers of oxidative phosphorylation, are shown to differ from artificial ones in that they fail to increase conductance of phospholipid bilayers which are permeable for the protonated form of fatty acids but impermeable for their anionic form. Recent studies have revealed that uncoupling by fatty acids in mitochondria is mediated by the ATP/ADP antiporter and, in brown fat, by thermogenin which is structurally very similar to the antiporter. It is suggested that both the ATP/ADP antiporter and thermogenin facilitate translocation of the fatty anions through the mitochondrial membrane.
Low content of mitochondrial ATPase in brown adipose tissue is the result of post‐transcriptional regulation
Authors: Houštěk Josef , Tvrdík Peter , Pavelka Stanislav , Baudyšová Marie
Published: November 2003

The mRNA levels of ATPase β, ATPase 6, cytochrome oxidase (COX) VIb and COX I subunits were found to be 2.4–13.8‐fold higher in brown adipose tissue (BAT) than in heart, skeletal muscle, brain and liver of mice. The comparison with tissue contents of ATPase and COX revealed that the selective, 5–11‐fold reduction of ATPase in BAT is not caused by decreased transcription of ATPase genes. Likewise, the ATPase β and COX VIb mRNA levels in cultured brown adipocytes were also not influenced by norepinephrine, which activated the expression of the UCP gene by two orders of magnitude. The results indicate that the biosynthesis of mitochondrial ATPase in BAT is post‐transcriptionally regulated.
Functional significance of aromatic amino acids from three peptide loops of the α7 neuronal nicotinic receptor site investigated by site‐directed mutagenesis
Authors: Galzi Jean-Luc , Bertrand Daniel , Devillers-Thiéry Anne , Revah Frédéric , Bertrand Sonia , Changeux Jean-Pierre
Published: November 2003

Three aromatic amino acids, Tyr92, Trp148 and Tyr187 belonging to three separate domains of the α7‐subunit of neuronal nicotinic acetylcholine receptor were mutated to phenylalanine, and the electrophysiological response of the resulting mutant receptors analyzed in the Xenopus oocyte expression system. All mutations significantly decreased the apparent affinities for acetylcholine and nicotine, and to a lesser extent, those for the competitive antagonists dihydro‐β‐erythroidine and α‐bungarotoxin. Other properties investigated, such as the voltage dependency of the ion response as well as its sensitivity to the open channel blocker QX222, were not significantly changed, indicating that the mutations affected selectively the recognition of cholinergic ligands by the receptor protein. The maximal rates for the rapid desensitization process were slightly modified, suggesting that the contribution of Tyr92, Trp148 and Tyr187 to the binding area might differ in the various conformations of the nicotinic receptor. Other mutations at nearby positions (S94N, W153F, G151D and G82E) did not affect the properties of the electrophysiological response. These data point to the functional significance of Tyr92, Trp148 and Tyr187 in the binding of cholinergic ligands and ion channel activation of the nicotinic receptor, thus supporting a multiple loop model [(1990) J. Biol. Chem. 265, 10430–10437] for the ligand binding area.
Plant basic 7 S globulin‐like proteins have insulin and insulin‐like growth factor binding activity
Authors: Komatsu Setsuko , Hirano Hisashi
Published: November 2003

Basic 7 S globulin (Bg) is a cysteine‐rich glycoprotein present in soybean seeds. Mature Bg is composed of high‐ and low‐kDa subunits linked by disulfide bonding. A ligand blotting experiment using [125I]insulin and [125I]insulin‐like growth factor‐I and ‐II showed that Bg subunits are able to bind not only to insulin but to insulin‐like growth factors‐I and ‐II. Bg‐like proteins from other legume species cross‐reacted with anti‐Bg antibody also bind to insulin and insulin‐like growth factors. Bg‐like protein in carrot cells was found to have insulin binding activity. Bg‐like proteins may be involved in an insulin‐like regulatory mechanism in many plant species.
On the substrate specificity of nitric oxide synthase
Authors: Hecker Markus , Walsh Desmond T. , Vane John R.
Published: November 2003

Nitric oxide (NO) synthase (NOS) activity in subcellular fractions from cultured endothelial cells (EC) and lipopolysaccharide‐activated J774.2 monocyte/macrophages was investigated by monitoring the NO‐mediated increase in intracellular cyclic GMP in LLC‐PK1 pig kidney epithelial cells. The constitutive NOS in EC (NOSc) was largely membrane‐bound, whereas the inducible NOS in J774.2 cells (NOS1) was equally distributed among cytosol and membrane(s). Both the cytosolic NOSc in EC and the membrane‐bound NOS1 in J774.2 cells were strictly Ca2+‐dependent, whereas the membrane‐bound NOSc in EC and the cytosolic NOS1 in J774.2 cells were not. L‐Homoarginine and L‐arginine‐containing small peptides, such as L‐arginyl‐L‐phenylalanine, replaced L‐arginine as a substrate for the NOSc in EC and the Ca2+‐independent NOS1 in J774.2 cells, but not the Ca2+‐dependent NOS1. Thus, irrespective of their intracellular localisation, at least three isoforms of NOS exist, which can be differentiated by their substrate specificity and Ca2+‐dependency.
Evidence for a Competitive‐Displacement Model for the initiation of protein synthesis involving the intermolecular hybridization of 5 S rRNA, 18 S rRNA and mRNA
Authors: Sarge Kevin D. , Maxwell E.Stuart
Published: November 2003

We have previously shown that a 5′‐terminal region of mouse 5 S rRNA can base‐pair in vitro with two distinct regions of 18 S rRNA. Further analysis reveals that these 5 S rRNA‐complementary sequences in 18 S rRNA also exhibit complementarity to the Kozak consensus sequence surrounding the mRNA translational start site. To test the possibility that these 2 regions in 18 S rRNA may be involved in mRNA binding and translational initiation, we have tested, using an in vitro translation system, the effects of DNA oligonucleotides complementary to these 18 S rRNA sequences on protein synthesis. Results show that an oligonucleotide complementary to one 18 S rRNA region does inhibit translation at the step of initiation. We propose a Competitive‐Displacement Model for the initiation of translation involving the intermolecular base‐pairing of 5 S rRNA 18 S rRNA and mRNA.
Trimeric G‐proteins of the trans‐Golgi network are involved in the formation of constitutive secretory vesicles and immature secretory granules
Authors: Barr Francis A. , Leyte Anja , Mollner Stefan , Pfeuffer Thomas , Tooze Sharon A. , Huttner Wieland B.
Published: November 2003

Non‐hydrolysable analogues of GTP, such as GTPγS and GMP‐PNP, have previously been shown to inhibit the formation of constitutive secretory vesicles (CSVs) and immature secretory granules (ISGs) from the trans‐Golgi network (TGN). Using a cell‐free system, we show here that the formation of these vesicles is also inhibited by [AIF4], a compound known to act on trimeric G‐proteins. Addition of highly purified G‐protein βγ subunits stimulated, in a differential manner, the cell‐free formation of both CSVs and ISGs. ADP‐ribosylation experiments revealed the presence of a pertussis toxin‐sensitive G‐protein α subunit in the TGN. We conclude that trimeric G‐proteins regulate the formation of secretory vesicles from the TGN.
The potent vasodilating and guanylyl cyclase activating dinitrosyl‐iron(II) complex is stored in a protein‐bound form in vascular tissue and is released by thiols
Authors: Mülsch Alexander , Mordvintcev Peter , Vanin Anatoly F. , Busse Rudi
Published: November 2003

We studied the biological activity, stability and interaction of dinitrosyl‐iron(II)‐L‐cysteine with vascular tissue. Dinitrosyl‐iron((II)‐L‐cysteine was a potent activator of purified soluble guanylyl cyclase (EC50 (nM with and 100 nM without superoxide dismutase) and relaxed noradrenaline‐precontracted segments of endothelium‐denuded rabbit femoral artery (EC50 10 nM superoxide dismutase). Pre‐incubation (5 min; 310 K) of endothelium‐denuded rabbit aortic segments with dinitrosyl‐iron(II)‐L‐cysteine (0.036–3.6 mM) resulted in a concentration‐dependent formation of a dinitrosyl‐iron(II complex with protein thiol groups, as detected by ESR spectroscopy. While the complex with proteins was stable for 2 h at 310 K, dinitrosyl‐iron(II)‐L‐cysteine in aqueous solution (30–360 μM) decomposed completely within 15 min, as indicated by disappearance of its isotropic ESR signal at g
av = 2.03 (293 K). Aortic segments pre‐incubated with dinitrosyl‐iron(II)‐L‐cysteine released a labile vasodilating and guanylyl cyclase activating factor. Perfusion of these segments with N‐acetyl‐L‐cysteine resulted in the generation of a low molecular weight dinitrosyl‐iron(II)‐dithiolate from the dinitrosyl‐iron(II) complex with proteins, as revealed by the shape change of the ESR signal at 293 K. The low molecular weight dinitrosyl‐iron(II)‐dithiolate accounted to an enhanced guanylyl cyclase activation and vasodilation induced by the aortic effluent. We conclude that nitric oxide (NO) produced by, or acting on vascular cells can be stabilized and stored as a dinitrosyl‐iron(II) complex with protein thiols, and can be released from cells in the form of a low molecular weight dinitrosyl‐iron(II)‐dithiolate by intra‐ and extracellular thiols.
Phorbol ester stimulation of pancreatic β‐cell replication, polyamine content and insulin secretion
Authors: Sjöholm Åke
Published: November 2003

Long‐term effects of the protein kinase C activating phorbol ester, TPA, on pancreatic β‐cell proliferation and insulin production were investigated It was found that β‐cell replication and long‐term insulin secretion were enhanced in TPA‐treated islets. This was not accompanied by a corresponding increase in (pro)insulin biosynthesis, presumably contributing to the lowered islet insulin content. TPA also increased islet polyamine content but when this increase was prevented by blocking polyamine synthesis, DNA replication and insulin secretion remained elevated. These findings indicate that TPA stimulates β‐cell replication and insulin secretion and suggest a stimulatory role for protein kinase C, but not for polyamines, in these processes.
Pyridoindole stobadine is a potent scavenger of hydroxyl radicals
Authors: Stefek M. , Benes L.
Published: November 2003

Stobadine is a potent scavenger of OH∗ radicals generated chemically in a free solution with k
2 higher than 1010 · M−1 s−1 as determined by two independent methods, namely destruction of deoxyribose and oxidation of 2‐keto‐4‐methiolbutyric acid (KMBA). The high efficacy of stobadine to prevent ethylene production from KMBA was observed also in enzymatic (xanthine‐xanthine oxidase‐driven Fenton) and membrane‐bound (NADPH‐dependent microsomal electron transfer) sources of OH∗ radicals.
Glycinebetaine enhances and stabilizes the evolution of oxygen and the synthesis of ATP by cyanobacterial thylakoid membranes
Authors: Mamedov M.D. , Hayashi H. , Wada H. , Mohanty P.S. , Papageorgiou G.C. , Murata N.
Published: November 2003

Glycinebetaine (betaine), an osmoregulant in halophilic plants, stabilized the evolution of oxygen and the synthesis of ATP by thylakoid membranes from the cyanobacterium Synechocystis PCC6803 when it was present during the preparation and incubation of the thylakoid membranes. Moreover, betaine enhanced the evolution of oxygen and the synthesis of ATP when present during assays. When betaine at 1.0 M was present during the preparation of thylakoid membranes and during the measurement of activity, the rate of evolution of oxygen was equivalent to that of intact cells.
The rate of ATP‐synthesis as a function of ΔpH and Δψ catalyzed by the active, reduced H+‐ATPase from chloroplasts
Authors: Junesch Ulrike , Gräber Peter
Published: November 2003

The H+‐ATPase from chloroplasts was brought into the active, reduced state. Then, an electrochemical potential difference of protons across the thylakoid membranes was generated by an acid‐base transition, ΔpH, combined with a K+/valinomycin diffusion potential, Δψ. The initial rate of ATP synthesis was measured with a rapid‐mixing quenched‐flow apparatus in the time‐range between 20–150 ms. The rate of ATP synthesis depends in a sigmoidal way on ΔpH. Increasing diffusion potentials shifts the ΔpH‐dependencies to lower ΔpH values. Analysis of the data indicate that the rate of ATP synthesis depends on the electrochemical potential difference of protons irrespective of the relative contribution of ΔpH and Δψ.
The sexual inducer of Volvox carteri
Authors: Haas Elke , Sumper Manfied
Published: November 2003

The DNA sequence coding for the sexual inducer glycoprotein of Volvox carteri and its N‐terminal signal peptide was placed under the control of the repressible acid phosphatase promoter of the yeast Saccharomyces cerevisiae in a yeast‐E. coli shuttle vector. Yeast transformed by this construct synthesized and secreted into the culture medium biologically active inducer in amounts two to three orders of magnitude higher than observed in the Volvox system.
Effects of high carbohydrate and high fat diet on plasma metabolite levels and on iv glucose tolerance test in intact and neutered male cats
Authors: Thiess S. , Becskei C. , Tomsa K. , Lutz T.A. , Wanner M.
Published: November 2003

To elucidate the impact of dietary influence on carbohydrate and lipid metabolism and on the development of diabetes mellitus in the carnivorous cat, a 3 weeks feeding trial was carried out on six sexually intact and six neutered adult male cats. The effects of two isonitrogenic diets, differing in carbohydrate and fat content, were investigated on plasma metabolite levels in a 24-h blood sampling trial. Plasma leptin concentrations were also determined at the beginning and at the end of the 24-h trial. Glucose and insulin response was measured in an iv glucose tolerance test. A 5 days long digestion trial was also performed, which revealed a high digestion capacity of both fat and carbohydrates in cats. The high fat diet induced a significant rise in the plasma triglyceride, FFA, β-hydroxybutyrate and cholesterol concentration, while the elevation in the glucose level did not reach significance. In the glucose tolerance test no significant difference was found between the neutered and intact cats. However, independently of the sexual state, the cats on the high fat diet showed a slightly elongated glucose clearance and reduced acute insulin response to glucose administration. This is indicative of diminished pancreatic insulin secretion and/or β-cell responsiveness to glucose. The results of this preliminary study may be the impetus for a long-term study to find out whether it is rather the fat rich ration than carbohydrate rich diet that is expected to impair glucose tolerance and thus might contribute to the development of diabetes mellitus in cats. Whether the alteration in glucose metabolism is due to altered leptin levels remains to be determined.
Amadori‐glycated phosphatidylethanolamine induces angiogenic differentiations in cultured human umbilical vein endothelial cells
Authors: Oak Jeong-Ho , Nakagawa Kiyotaka , Oikawa Shinichi , Miyazawa Teruo
Published: November 2003

Glycation has been implicated in the endothelial dysfunction that contributes to both diabetes‐ and aging‐associated vascular complications. The aim of the present study was to determine whether Amadori‐glycated phosphatidylethanolamine (Amadori‐PE), a lipid‐linked glycation compound that is formed at an increased rate in hyperglycemic states, affected proliferation, migration and tube formation of cultured human umbilical vein endothelial cells (HUVEC). Amadori‐PE at a low concentration of less than 5 μM significantly enhanced these three factors involved in angiogenesis. Furthermore, stimulation of HUVEC with Amadori‐PE resulted in secretion of matrix metalloproteinase 2 (MMP‐2), a pivotal enzyme in the initial step of angiogenesis. Our results demonstrated for the first time that Amadori‐PE may be an important compound that promotes vascular disease as a result of its angiogenic activity on endothelial cells. We also demonstrated that MMP‐2 is a primary mediator of Amadori‐PE‐driven angiogenesis.
Involvement of Akt in mitochondria‐dependent apoptosis induced by a cdc25 phosphatase inhibitor naphthoquinone analog
Authors: Kim Hae Jong , Kang Seung Koo , Mun Jung Yee , Chun Young Jin , Choi Kyung Hee , Kim Mie Young
Published: November 2003

Vitamin K‐related analogs induce growth inhibition via a cell cycle arrest through cdc25A phosphatase inhibition in various cancer cell lines. We report that 2,3‐dichloro‐5,8‐dihydroxy‐1,4‐naphthoquinone (DDN), a naphthoquinone analog, induces mitochondria‐dependent apoptosis in human promyelocytic leukemia HL‐60 cells. DDN induced cytochrome c release, Bax translocation, cleavage of Bid and Bad, and activation of caspase‐3, ‐8, ‐9 upon the induction of apoptosis. Cleavage of Bid, the caspase‐8 substrate, was inhibited by the broad caspase inhibitor z‐Val‐Ala‐Asp(OMe)‐fluoromethylketone (zVAD‐fmk), whereas cytochrome c release was not affected, suggesting that activation of caspase‐8 and subsequent Bid cleavage occur downstream of cytochrome c release. DDN inhibited the activation of Akt detected by decreasing level of phosphorylation. Overexpression of constitutively active Akt protected cells from DDN‐induced apoptosis, while dominant negative Akt moderately enhanced cell death. Furthermore, Akt prevented release of cytochrome c and cleavage of Bad in DDN‐treated HL‐60 cells. Taken together, DDN‐induced apoptosis is associated with mitochondrial signaling which involves cytochrome c release via a mechanism inhibited by Akt.
Role of secretory and cytosolic phospholipase A2 enzymes in lysophosphatidylcholine‐stimulated monocyte arachidonic acid release
Authors: Oestvang Janne , Anthonsen Marit W. , Johansen Berit
Published: November 2003

To determine if lysophosphatidylcholine (lysoPC) is able to induce proinflammatory changes in monocytes, its ability to stimulate arachidonic acid (AA) release, a product of phospholipase A2 (PLA2) activity, has been analyzed. LysoPC increased AA release in THP‐1 and Mono Mac6 cells in a time‐ and concentration‐dependent manner. The monocytes expressed both secretory and cytosolic PLA2 enzymes and AA release was strongly reduced by cellular pretreatment with different PLA2 inhibitors and by pertussis toxin, an inhibitor of Gi‐protein activation. This indicates that both cytosolic and secretory PLA2 enzymes regulate specific lysoPC receptor‐induced AA release, suggesting lysoPC participation in monocyte proinflammatory activation.
Mechanistic studies of the SufS–SufE cysteine desulfurase: evidence for sulfur transfer from SufS to SufE
Authors: Ollagnier-de-Choudens Sandrine , Lascoux David , Loiseau Laurent , Barras Frédéric , Forest Eric , Fontecave Marc
Published: November 2003

SufS is a cysteine desulfurase of the suf operon shown to be involved in iron–sulfur cluster biosynthesis under iron limitation and oxidative stress conditions. The enzyme catalyzes the conversion of L‐cysteine to L‐alanine and sulfide through the intermediate formation of a protein‐bound cysteine persulfide in the active site. SufE, another component of the suf operon, has been previously shown to bind tightly to SufS and to drastically stimulate its cysteine desulfurase activity. Working with Escherichia coli proteins, we here demonstrate that a conserved cysteine residue in SufE at position 51 is essential for the SufS/SufE cysteine desulfurase activity. Mass spectrometry has been used to demonstrate (i) the ability of SufE to bind sulfur atoms on its cysteine 51 and (ii) the direct transfer of the sulfur atom from the cysteine persulfide of SufS to SufE. A reaction mechanism is proposed for this novel two‐component cysteine desulfurase.
GnRHa flare and IVF pregnancy rates
Authors: Confino E. , Zhang X. , Kazer R.R.
Published: November 2003

Objectives: GnRH agonist administered early in the menstrual cycle (flare) causes an endogenous discharge of FSH and LH. Flare has been used in conjunction with gonadotropin ovarian stimulation for IVF ‘poor responders’. There is an ongoing controversy regarding whether flare protocols improve pregnancy rates in ‘poor responders’. The current study was designed to compare a GnRHa flare protocol with long suppression GnRHa IVF in ‘poor responders’. Methods: Seventy‐three newly diagnosed poor responders who failed long GnRHa suppression IVF attempts were compared retrospectively with 128 age‐matched IVF patients previously known poor ovarian responders treated with a long GnRHa suppression protocol. ‘Poor responders’ consisted of patients with peak E2 less than 1000 pg/ml and/or less than five mature follicles with diameter >15 mm on the day of hCG administration. Student's t‐test was used to analyze the data and the chi‐squared test was used to compare fertilization and pregnancy rates. Results: The flare protocol produced higher peak E2 levels (1647±747 vs. 720±258 mIU/ml, P<0.05) and a larger number of mature follicles (5.8±2.2 vs. 4.0±1.0 P<0.05) in the study vs. the control group. A 30% pregnancy rate was achieved during this second IVF attempt using GnRHa flare protocol in the study group vs. 37 in the control group (P>0.05, NS). Conclusions: A comparison between the flare protocol group and the age‐matched control group of poor ovarian responders subject to down regulation protocol, revealed higher peak E2 levels and more mature follicles, respectively. However, both groups yielded comparable pregnancy rates. The use of high dose gonadotropin treatment in our study groups seems to be the only explanation for their subsequent successful outcome. We concluded that GnRH agonist flare protocol does not result in better IVF outcome compared with long GnRH agonist suppression protocol in IVF poor responders.
Clinical trials update from the European Society of Cardiology: CHARM, BASEL, EUROPA and ESTEEM
Authors: Coletta Alison P. , Cleland John G.F. , Freemantle Nick , Loh Huan , Memon Anwar , Clark Andrew L.
Published: November 2003

This article contains a series of reports on recent research developments in the field of heart failure. Reports of key presentations made at the European Society of Cardiology meeting, held in Vienna, Austria, between 30 August and 3 September 2003 are reported. In the CHARM study, candesartan reduced cardiovascular deaths and hospital admissions for heart failure, both in patients who were already taking an ACE‐inhibitor and in those who were ACE intolerant. However, results in patients with preserved left ventricular function were less conclusive. The BASEL study supports the use of B‐type natriuretic peptide testing to confirm the diagnosis of heart failure in patients presenting with acute dyspnoea. In EUROPA, the largest ever study of secondary prevention of coronary artery disease, long‐term treatment with perindopril reduced the incidence of cardiovascular death, myocardial infarction (MI) and cardiac arrest. The ESTEEM study showed that the oral thrombin inhibitor ximelagatran plus aspirin was more effective than aspirin alone in the prophylaxis of major cardiovascular events following MI.
Efficacy and safety of oral candesartan cilexetil in patients with congestive heart failure
Authors: Matsumori Akira ,   on behalf of the assessment of response to candesartan in heart failure in Japan (ARCH‐J) study investigators
Published: November 2003

Background:

Candesartan cilexetil is a new angiotensin II receptor blocker with a high affinity for the angiotensin II‐subtype 1 receptor.

Aims:

This 6‐month study examined the safety and efficacy of candesartan cilexetil, 8 mg once daily, to prevent the progression of congestive heart failure (CHF).

Methods:

This randomised, double‐blind, placebo‐controlled study enrolled 305 patients with CHF who were not receiving ACE inhibitor therapy. The composite primary efficacy endpoint was progression of CHF or addition or dose escalation of CHF medications. The secondary endpoints were incidence of cardiovascular events and changes in left ventricular function.

Results:

The study was prematurely terminated after the second interim safety analysis. The incidence of confirmed progression of CHF was significantly lower in the candesartan group (7.4%) than in the placebo group (22.2%), with a risk reduction of 66.7% and a risk difference of −14.8% (95% CI: −22.8 to −6.8%, P<0.001). Cardiovascular events were also significantly lower during treatment with candesartan than with placebo (10.8% vs. 22.9%) with a risk reduction of 52.8% and a risk difference of −12.1% (95% CI: −20.6 to −3.6%, P<0.01). The actively treated group had a significant improvement in hemodynamics. Candesartan cilexetil was well tolerated.

Conclusion:

Candesartan cilexetil, 8 mg/day, significantly reduced the progression of CHF when compared with placebo.
Binding of Porphyrins by the Tumor-Specific Lectin, Jacalin [Jack Fruit (Artocarpus integrifolia) Agglutinin]
Authors: Komath Sneha Sudha , Bhanu Kancheenadham , Maiya Bhaskar G. , Swamy Musti J.
Published: November 2003

Jacalin (Artocarpus integrifolia agglutinin) specifically recognizes thetumor-associated T-antigenic disaccharide structure, Galγ13GalNAc. Porphyrins and their derivatives are currently used asphotosensitizers in photodynamic therapy to treat malignant tumors. In thisstudy, the interaction of several free base porphyrins and their metalderivatives with jacalin is investigated by absorption and fluorescencespectroscopy. Each lectin subunit was found to bind one porphyrin moleculeand the association constants were estimated to be in the range of 2.4 × 103M−1 to 1.3 × 105M−1 at room temperaturefor the interaction of different porphyrins with jacalin. These values arein the same range as those obtained for the interaction of monosaccharidesto jacalin. Both free lectin and lectin saturated with the specificsaccharide were found to bind different porphyrins with comparable bindingstrength indicating that porphyrin binding takes place at a site differentfrom the sugar binding site. Further, both anionic and cationic porphyrinswere found to interact with the lectin with comparable affinity, clearlyindicating that the charge on the porphyrin does not play any role in thebinding process and that most likely the interaction is mediated byhydrophobic forces. These results suggest that jacalin and other lectins maypotentially be useful for targeted delivery of porphyrins to tumor tissuesin photodynamic therapy.
K+ Uptake by Fermenting Escherichia coli Cells: pH Dependent Mode of the TrkA System Operating
Authors: Trchounian Armen , Kobayashi Hiroshi
Published: November 2003

Escherichia coli accumulates K+ by means of multiple transportsystems, of which TrkA is the most prominent at neutral and alkalinepH while Kup is major at acidic pH. In the present study, K+ uptakewas observed with cells grown under fermentative conditions at an initialpH of 9.0 and 7.3 (the medium pH decreased to 8.4 and 6.8, respectively, during the mid-logarithmic growth phase), washed with distilled water andresuspended in a K+ containing medium at pH 7.5 in the presence ofglucose. The kinetics for this K+ uptake and the amount of K+accumulated by the wild type and mutants having a functional TrkA or Kup could confirm that K+ uptake by E. coli grown either at pH 9.0or pH 7.3 occurs mainly through TrkA. The following results distinguishpH dependent mode of TrkA operating: (1) K+ uptake was inhibited byDCCD in cells grown either at pH 9.0 or pH 7.3, although the stoichiometryof K+ influx to DCCD-inhibited H+ efflux for bacteria grownat pH 9.0 varied with external K+ concentration, but remained constantfor cells grown at pH 7.3; (2) K+ uptake was observed with an atpDmutant grown at pH 9.0 but not at pH 7.3; (3) The DCCD-inhibited H+efflux was increased 8-fold less by 5 mM K+ added into a K+ freemedium for bacteria grown at pH 9.0 than that for cells grown at pH 7.3;(4) the DCCD-inhibited ATPase activity of membrane vesicles from bacteriagrown at pH 9.0 was reduced a little in the presence of 100 mM K+, but stimulated more than 2.4-fold at pH 7.3.
Mutations in the low‐density‐lipoprotein receptor gene in German patients with familial hypercholesterolaemia
Authors: Weiss N. , Binder G. , Keller C.
Published: November 2003

Familial hypercholesterolaemia (FH) is an autosomal dominant disorder of lipid metabolism characterized by elevated low‐density lipoproteins (LDL), the formation of tendon and skin xanthomata and the development of premature coronary atherosclerosis. It is caused by a defect in the receptor‐mediated hepatic uptake of LDL due to mutations in the LDL receptor. In 25 FH families with a total of 160 members and in two individuals without available relatives, all of German origin, we identified LDL receptor mutations by a multiplex‐PCR‐based single‐strand conformation polymorphism method followed by direct sequencing. Of the 24 mutations found, 15 are missense mutations, 2 are nonsense mutations, 4 are small deletions or insertions leading to frameshifts, 2 are an in‐frame insertion and deletion, respectively, and one is a splice site mutation. Propositi carrying mutations that are known to completely abolish receptor function (nonsense and frameshift mutations, missense mutation V480M) had significantly higher untreated total and LDL‐cholesterol levels compared to those patients carrying missense and in‐frame insertion mutations of unknown functional consequence, which may lead to either reduced or completely abolished receptor function (11.30±1.64 vs 9.76±1.50 mmol/L, and 9.39±1.23 vs 7.99±1.45 mmol/L, respectively). These results confirm the clinical and molecular heterogeneity of FH and the influence of different functional classes of mutations on lipid values.
Trifunctional protein deficiency: Three families with significant maternal hepatic dysfunction in pregnancy not associated with E474Q mutation
Authors: Chakrapani A. , Olpin S. , Cleary M. , Walter J. H. , Wraith J. E. , Besley G. T. N.
Published: November 2003

We report five families with trifunctional protein deficiency in which, during pregnancy, three mothers experienced significant hepatic disease when carrying an affected fetus. Diagnoses were based on increased levels of long‐chain hydroxyacylcarnitines and deficiencies of 3‐hydroxyacyl‐CoA dehydrogenase (LCHAD) and 3‐ketoacyl‐CoA thiolase activity in fibroblasts. All affected infants lacked the common E474Q mutation associated with isolated LCHAD deficiency. This mutation is thought to be a predisposing factor for maternal hepatic disease in pregnancy. Our findings suggest that other defects in this enzyme complex might be responsible for maternal hepatic complications in pregnancy.
Hepatocellular carcinoma despite long‐term survival in chronic tyrosinaemia I
Authors: Kim S. Z. , Kupke K. G. , Ierardi‐Curto L. , Holme E. , Greter J. , Tanguay R. M. , Poudrier J. , D'Astous M. , Lettre F. , Hahn S. H. , Levy H. L.
Published: November 2003

Tyrosinaemia I (fumarylacetoacetate hydrolase deficiency) is an autosomal recessive inborn error of tyrosine metabolism that produces liver failure in infancy or a more chronic course of liver disease with cirrhosis, often complicated by hepatocellular carcinoma, in childhood or early adolescence. We studied a 37‐year‐old woman with tyrosinaemia I whose severe liver disease in infancy and rickets during childhood resolved with dietary therapy. From 14 years of age she resumed an unrestricted diet with the continued presence of the biochemical features of tyrosinaemia, yet maintained normal liver function. In adult years she accumulated only small amounts of succinylacetone. Despite this evolution to a mild biochemical and clinical phenotype, she eventually developed hepatocellular carcinoma. Her fumarylacetoacetate hydrolase genotype consists of a splice mutation, IVS6−1g>t, and a novel missense mutation, Q279R. Studies of resected liver demonstrated the absence of hydrolytic activity and of immunological expression of fumarylacetoacetate hydrolase in liver tumour. In nontumoral areas, however, 53% of normal hydrolytic activity and immunologically present fumarylacetoacetate hydrolase was found. This case demonstrates the high risk of liver cancer in tyrosinaemia I even in a seemingly favourable biological environment.
Plasma creatinine assessment in creatine deficiency: A diagnostic pitfall
Authors: Verhoeven N. M. , Guérand W. S. , Struys E. A. , Bouman A. A. , van der Knaap M. S. , Jakobs C.
Published: November 2003

Guanidinoacetate methyltransferase (GAMT) deficiency (creatine deficiency syndrome) is a recently discovered inborn error of creatine biosynthesis. Affected patients have elevated concentrations of guanidinoacetate, the metabolic precursor of creatine, in urine, plasma and cerebrospinal fluid. In addition, urinary creatinine excretion and plasma creatinine concentration are decreased. For biochemical evaluation of patients suspected to suffer from GAMT deficiency, correct quantification of creatinine in plasma is important. Here we report our experience with different quantification techniques. We found that creatinine in plasma from two GAMT‐deficient patients appeared normal when measured by the Jaffé method but was decreased when measured enzymatically or by HPLC. The apparently normal levels of creatinine as measured by the Jaffé method were not caused by guanidinoacetate. In urine, the Jaffé method and the enzymatic method gave similar results, indicating that in urine no false elevations of creatinine can be expected. As the Jaffé method is still widely used for routine plasma creatinine measurements, it is important to realize it cannot be used to exclude GAMT deficiency.
Treating glucosphingolipid disorders by chemotherapy: Use of approved drugs and over‐the‐counter remedies
Authors: Radin N. S.
Published: November 2003

The accumulation of a glucosphingolipid (GSL) in individuals lacking an adequate level of hydrolase activity could be minimized by chemotherapeutic measures that slow the formation of the GSL and stimulate the defective hydrolase. By achieving a balance in the rates of formation and breakdown, one should be able to alleviate the symptoms of excess storage and achieve a satisfactory accommodation. While several drugs seem to be specifically suitable for this purpose, only one of these has been approved for human use. However, less effective drugs and over‐the‐counter substances are available for human use and may prove satisfactory for a few years until better ones are made available. The proposed materials and the evidence behind the recommendations are presented in this paper.
Modifikation des Computerspiels Quake III Arena zur Durchführung psychologischer Experimente in einer virtuellen 3D-Umgebung
Authors: Hartig Johannes , Frey Andreas , Ketzel André
Published: November 2003

Zusammenfassung. Computerspiele können eine Bereicherung experimentell-psychologischer Untersuchungen darstellen. Existierende Computerspiele genügen jedoch hinsichtlich der Möglichkeiten zur Datenaufzeichnung und Variation der Spielinhalte oft nicht experimentellen Ansprüchen. Eine Modifikation des Computerspiels Quake III Arena sollte diese Nachteile überwinden. Eine selbst erstellte virtuelle 3D-Umgebung wurde bei einer ersten Erprobung an 85 Proband/inn/en danach beurteilt, ob sie im praktischen Einsatz zuverlässig funktioniert und ob die Proband/inn/en mit unterschiedlich komplexen Anforderungen zurechtkommen. Die Ergebnisse sprechen dafür, dass insbesondere virtuelle 3D-Umgebungen niedriger Komplexität für psychologische Experimente geeignet sind. Damit stellen Modifikationen existierender Computerspiele vielfältige neue Möglichkeiten für die experimentell-psychologische Forschung zur Verfügung.
Paleomagnetic results from the Cambrian and Ordovician sediments of Bornholm (Denmark) and Southern Sweden and paleogeographical implications for Baltica
Authors: Lewandowski Marek , Abrahamsen Niels
Published: November 2003

If apparent polar wander paths (APWP) cross, the question arises how to prove the older magnetization to be primary and not just a younger overprint. This problem is typically met in areas affected by percolating mineralizing fluids and/or heating due to a younger regional igneous activity. The Permian magnetic overprint is the classical example. Earlier paleomagnetic studies over the Lowermost Cambrian Nekso Sandstone Fm (NSF) of Bornholm (Denmark) yielded a characteristic remanent magnetization (ChRM) similar to the Permian directions for Baltica. Since a possible reason could be a chemical overprint, we checked whether this phenomenon did take place on a regional scale. Some samples therefore were collected from other Lower Cambrian clastics of Bornholm and Southern Scandinavia. In result we show that the well‐grouped and stable ChRM of the NSF contrasts with fairly chaotic, soft, and badly preserved magnetizations of the Balka, Hardeberga, Mickwitzia, and Lingulid sandstones of Bornholm and Southern Sweden, thus not indicating widespread paleomagnetic overprint. We demonstrate that the ChRM of the NSF is most probably of syndepositional/early diagenetic origin and its similarity to the Permian direction for Baltica is only casual. We propose a normal polarity and a near‐equatorial position on the Southern Hemisphere for Baltica in the early Cambrian time, as well as a more complicated trend of the APWP for this paleocontinent than envisaged by other authors. Paleomagnetic results from the Arenigian limestones of the Laesaa Formation (Bornholm) that yield excellently defined but most probably only secondary components are also presented.
Crystallization of atmospheric sulfate‐nitrate‐ammonium particles
Authors: Martin Scot T. , Schlenker Julie C. , Malinowski Adam , Hung Hui‐Ming , Rudich Yinon
Published: November 2003

Relative humidity (RH) history and chemical composition determine whether atmospheric particles are liquid or solid. Particle physical state affects many climatic and environmental phenomena such as radiative transfer, visibility, and heterogeneous chemistry. Here we report the crystallization RH (CRH) at 293 K of particles throughout the entire sulfate‐nitrate‐ammonium composition space, and the new laboratory data are expressed as an empirical polynomial. Particles with compositions close to ammonium sulfate crystallize near 30% RH. Such particles are common in the boundary layer, including the eastern USA and East Asia though not Europe. Our measurements show the formation of several solids within the same particle for compositions enriched in nitrate or somewhat acidic, although the CRH is under 30%. The CRH for homogeneous nucleation is 40 to 55% below the deliquescence RH (DRH) for most chemical compositions. Our new results provide essential data for the incorporation of particle physical state in global models of chemistry and climate.
Short‐term variation of CO2 flux in relation to environmental controls in an alpine meadow on the Qinghai‐Tibetan Plateau
Authors: Gu Song , Tang Yanhong , Du Mingyuan , Kato Tomomichi , Li Yingnian , Cui Xiaoyong , Zhao Xingquan
Published: November 2003

The alpine meadow ecosystem on the Qinghai‐Tibetan Plateau may play a significant role in the regional carbon cycle. To assess the CO2 flux and its relationship to environmental controls in the ecosystem, eddy covariance of CO2, H2O, and energy fluxes was measured with an open‐path system in an alpine meadow on the plateau at an elevation of 3,250 m. Net ecosystem CO2 influx (Fc) averaged 8.8 g m−2 day−1 during the period from August 9 to 31, 2001, with a maximum of 15.9 g m−2 day−1 and a minimum of 2.3 g m−2 day−1. Daytime Fc averaged 16.7 g m−2 day−1 and ranged from 10.4 g m−2 day−1 to 21.7 g m−2 day−1 during the study period. For the same photosynthetic photon flux density (PPFD), gross CO2 uptake (Gc) was significantly higher on cloudy days than on clear days. However, mean daily Gc was higher on clear days than on cloudy days. With high PPFD, Fc decreased as air temperature increased from 10°C to 23°C. The greater the difference between daytime and nighttime air temperatures, the more the sink was strengthened. Daytime average water use efficiency of the ecosystem (WUEe) was 8.7 mg (CO2)(g H2O)−1; WUEe values ranged from 5.8 to 15.3 mg (CO2)(g H2O)−1. WUEe increased with the decrease in vapor pressure deficit. Daily albedo averaged 0.20, ranging from 0.19 to 0.22 during the study period, and was negatively correlated with daily Fc. Our measurements provided some of the first evidence on CO2 exchange for a temperate alpine meadow ecosystem on the Qinghai‐Tibetan Plateau, which is necessary for assessing the carbon budget and carbon cycle processes for temperate grassland ecosystems.