bluuebunny/crossref_metadata_2025 huggingface dataset:
Anoikis is regulated by BCL‐2‐independent pathways in human prostate carcinoma cells
Authors: Bondar Victor M. , McConkey David J.
Published: August 2002

Background

Loss of contact with the extracellular matrix (ECM) triggers a specialized form of apoptosis known as “anoikis” in normal epithelial cells. Dependence on adhesion to ECM is often lost in transformed cells, and the degree of anchorage independence may vary in non‐metastatic and metastatic cancer cells. BCL‐2 oncoprotein overexpression correlates with the progression and metastases of prostate cancer.

Materials and Methods

We studied anoikis in suspension cultures of PC‐3 and LNCaP prostate carcinoma cells selected for enhanced metastatic potential in vivo and in PC‐3 and LNCaP cells stably transfected with BCL‐2. Apoptosis‐associated DNA fragmentation was measured by agarose gel electrophoresis and propidium iodide staining and flow cytometry. Expression of BCL‐2 family polypeptides was determined by immunoblotting.

Results

Non‐metastatic PC‐3P cells were significantly more sensitive to anoikis than the metastatic PC‐3 variants (PC‐3M, PC‐3M‐PRO‐4, and PC‐3M‐LN‐4), but anoikis resistance did not correlate with metastatic potential in LNCaP‐derived cell lines. Expression of BCL‐2 was higher in metastatic PC‐3 and LNCaP subclones compared to isogenic non‐metastatic cells, but these levels were not affected by anoikis. Enforced overexpression of BCL‐2 did not protect either PC‐3P or LNCaP‐PRO‐5 cells from anoikis, even though it rendered them resistant to thapsigargin and inhibited cytochrome c release. Strikingly, cells that died of anoikis maintained their pretreatment levels of BCL‐2, whereas the cells that survived anoikis expressed much lower levels of the protein.

Conclusions

Sensitivity to anoikis is regulated by BCL‐2 independent mechanisms in LNCaP and PC‐3 prostate cancer cells. Prostate 51:42–49, 2002. © 2002 Wiley‐Liss, Inc.
PRAC: A novel small nuclear protein that is specifically expressed in human prostate and colon
Authors: Liu Xiu Fen , Olsson Pär , Wolfgang Curt D. , Bera Tapan K. , Duray Paul , Lee Byungkook , Pastan Ira
Published: August 2002

BACKGROUND

The database of human Expressed Sequence Tags (dbEST) provides a potential source for identification of tissue‐specific genes. This database contains sequences that originate from cDNA libraries from particular tumors, organs or cell types. In this report, we have used the EST database to identify PRAC, a novel gene specifically expressed in human Prostate, prostate cancer, Rectum And distal Colon.

METHODS

Using a computer based analysis, a cluster of sequence homologous ESTs was identified which contained ESTs derived only from human prostate cDNA libraries. The tissue specificity was examined by multiple tissue RNA dot blots and RT‐PCR. The PRAC transcript and protein was identified using Northern blot analysis, RACE‐PCR, primer extension, and western blot.

RESULTS

PRAC encode a 382 nucleotide RNA found in prostate, rectum, distal colon, and in three prostate cancer cell lines; LNCaP, PC‐3 and DU145. This transcript encodes a 6 kDa nuclear protein. The PRAC gene is located on chromosome 17 at position 17q21, about 4 kbp downstream from the homeodomain Hoxb‐13 gene.

CONCLUSIONS

Our data proves that the EST database can be a useful tool for discovery of prostate‐specific genes. The nuclear localization, identification of potential phosphorylation sites, and possible cotranscription with the Hoxb‐13 gene suggest that PRAC may have a regulatory role in the nucleus. Prostate 47:125–131, 2001. © 2001 Wiley‐Liss, Inc.
Cell cycle checkpoint efficiency and cellular response to paclitaxel in prostate cancer cells
Authors: Lanzi Cinzia , Cassinelli Giuliana , Cuccuru Giuditta , Supino Rosanna , Zuco Valentina , Ferlini Cristiano , Scambia Giovanni , Zunino Franco
Published: August 2002

BACKGROUND

Defects in the cell cycle machinery of prostate cancer cells might impair the efficiency of cell cycle checkpoints and affect the cell response to chemotherapeutic drugs. We examined the relationship between the status of microtubule damage‐activated checkpoints and the response of hormone‐refractory prostate cancer cells to paclitaxel.

METHODS

The two cell lines DU145 and PC3 harboring defects at proteins involved in the regulation of checkpoints activated by microtubule damage were examined for cell sensitivity, apoptotic response, and efficiency of checkpoints in response to paclitaxel.

RESULTS

In spite of a comparable sensitivity to the antiproliferative effects of paclitaxel, DU145 and PC3 cells exhibited different cell cycle control at checkpoints activated by microtubule damage. A transient mitotic arrest was induced by the taxane in both cell lines. However, PC3 cells underwent a rapid mitotic slippage and displayed a defective postmitotic checkpoint as evidenced by the appearance of polyploid cells. In this cell line, paclitaxel‐induced cell death was a slow and delayed event, occurring also after S‐phase re‐entry. The mitotic checkpoint appeared to be more stringent in DU145 cells compared to PC3 cells. Moreover, despite the expression of mutated proteins involved in the prevention of DNA endoreduplication (p53, pRb, and p16INK4A), these cells did not progress into the cell cycle but efficiently underwent apoptosis by 24 hr. Such a response of DU145 cells was associated with phosphorylation of the p21WAF1 protein.

CONCLUSIONS

These observations evidence that activation of checkpoints following microtubule damage in prostate cancer may be regulated through complex mechanisms possibly involving p21WAF1. Our findings support that the status of cell cycle checkpoints might affect the modality of cell death. However, the relevance of the mode of cell death for the sensitivity to taxanes remains to be determined. Prostate 48:254–264, 2001. © 2001 Wiley‐Liss, Inc.
Androgen depletion activates telomerase in the prostate of the nonhuman primate, Macaca mulatta
Authors: Ravindranath Neelakanta , Ioffe Sergey L. , Marshall Gary R. , Ramaswamy Suresh , Plant Tony M. , Dym Martin
Published: August 2002

BACKGROUND

The activity of telomerase, an enzyme that synthesizes telomeric repeats at the ends of chromosomes, is not detectable in normal human prostate. However, the majority of human prostate cancers exhibit telomerase activity. Since androgens play a major role in prostate tumorigenesis, we investigated the effect of androgen‐depletion on the expression of telomerase activity in the prostate.

METHODS

Adult male rhesus monkeys were either bilaterally castrated or subjected to sham surgery (n = 5 each). Approximately 6 weeks later, the animals were killed and the different regions of the prostate gland were removed and frozen immediately. Telomerase activity was assayed using the telomeric repeat amplification protocol.

RESULTS

All five regions of the prostate from sham operated control animals failed to exhibit telomerase activity. In the castrated monkey, all regions of the prostate, except for the anterior lobe, expressed high levels of telomerase activity.

CONCLUSIONS

Our results indicate that in monkeys, androgen‐ablation leads to up‐regulation of telomerase activity. The negative‐regulation of telomerase activity by androgens is probably lost during prostate tumorigenesis. Prostate 49:79–89, 2001. © 2001 Wiley‐Liss, Inc.
Potential of mean force for protein–protein interaction studies
Authors: Jiang Lin , Gao Ying , Mao Fenglou , Liu Zhijie , Lai Luhua
Published: August 2002

Calculating protein–protein interaction energies is crucial for understanding protein–protein associations. On the basis of the methodology of mean‐field potential, we have developed an empirical approach to estimate binding free energy for protein–protein interactions. This knowledge‐based approach has been used to derive distance‐dependent free energies of protein complexes from a nonredundant training set in the Protein Data Bank (PDB), with a careful treatment of homology. We calculate atom pair potentials for 16 pair interactions, which can reflect the importance of hydrophobic interactions and specific hydrogen‐bonding interactions. The derived potentials for hydrogen‐bonding interactions show a valley of favorable interactions at a distance of ≈3 Å, corresponding to that of an established hydrogen bond. For the test set of 28 protein complexes, the calculated energies have a correlation coefficient of 0.75 compared with experimental binding free energies. The performance of the method in ranking the binding energies of different protein–protein complexes shows that the energy estimation can be applied to value binding free energies for protein–protein associations. Proteins 2002;46:190–196. © 2001 Wiley‐Liss, Inc.
Native and non‐native interactions along protein folding and unfolding pathways
Authors: Paci Emanuele , Vendruscolo Michele , Karplus Martin
Published: August 2002

Gō‐type models, which include only native contact interactions in the energy function, are being used increasingly to describe the protein folding reaction. To investigate the validity of such models, we determine the role of native and non‐native interactions along folding and unfolding pathways. For this purpose, we use a molecular mechanics energy function with an implicit solvation model (an effective energy function or potential of mean force) that can be expressed in a pairwise decomposable form. We find that for the native state and a wide range of other configurations, the contact energy is an accurate description, in part due to the cancellation of non‐zero contributions from more distant residues. However, significant errors in the energy are introduced for non‐native structures if the energy is calculated from the native contacts alone. Non‐native contacts tend to make a significant contribution, particularly for molten globules and collapsed states along the unfolding pathways. The implication of these results for the use of Gō‐type models in studies of protein folding are discussed. Proteins 2002;47:379–392. © 2002 Wiley‐Liss, Inc.
Increasing the precision of comparative models with YASARA NOVA—a self‐parameterizing force field
Authors: Krieger Elmar , Koraimann Günther , Vriend Gert
Published: August 2002

One of the conclusions drawn at the CASP4 meeting in Asilomar was that applying various force fields during refinement of template‐based models tends to move predictions in the wrong direction, away from the experimentally determined coordinates. We have derived an all‐atom force field aimed at protein and nucleotide optimization in vacuo (NOVA), which has been specifically designed to avoid this problem. NOVA resembles common molecular dynamics force fields but has been automatically parameterized with two major goals: (i) not to make high resolution X‐ray structures worse and (ii) to improve homology models built by WHAT IF. Force‐field parameters were not required to be physically correct; instead, they were optimized with random Monte Carlo moves in force‐field parameter space, each one evaluated by simulated annealing runs of a 50‐protein optimization set. Errors inherent to the approximate force‐field equation could thus be canceled by errors in force‐field parameters. Compared with the optimization set, the force field did equally well on an independent validation set and is shown to move in silico models closer to reality. It can be applied to modeling applications as well as X‐ray and NMR structure refinement. A new method to assign force‐field parameters based on molecular trees is also presented. A NOVA server is freely accessible athttp://www.yasara.com/serversProteins 2002;47:393–402. © 2002 Wiley‐Liss, Inc.
Comparison of different schemes to treat long‐range electrostatic interactions in molecular dynamics simulations of a protein crystal
Authors: Walser Regula , Hünenberger Philippe H. , van Gunsteren Wilfred F.
Published: August 2002

Eight molecular dynamics simulations of a ubiquitin crystal unit cell were performed to investigate the effect of different schemes to treat the long‐range electrostatic interactions as well as the need to include counter ions. A crystal system was chosen as the test system, because the higher charge density compared with a protein in solution makes it more sensitive to the way of treating the electrostatic interactions. Three different schemes of treating the long‐range interactions were compared: straight cutoff, reaction‐field approximation, and a lattice‐sum method (P3M). For each of these schemes, two simulations were performed, one with and one without the counter ions. Two additional simulations with a reaction‐field force and different initial placements of the counter ions were performed to examine the effect of the initial positions of the ions. The inclusion of long‐range electrostatic interactions using either a reaction‐field or a lattice‐sum method proved to be necessary for the simulation of crystals. These two schemes did not differ much in their ability to reproduce the crystallographic structure. The inclusion of counter ions, on the other hand, seems not necessary for obtaining a stable simulation. The initial positions of the ions have a visible but small effect on the simulation. Proteins 2001;44:509–519. © 2001 Wiley‐Liss, Inc.
A new method to model membrane protein structure based on silent amino acid substitutions
Authors: Briggs John A.G. , Torres Jaume , Arkin Isaiah T.
Published: August 2002

The importance of accurately modeling membrane proteins cannot be overstated, in lieu of the difficulties in solving their structures experimentally. Often, however, modeling procedures (e.g., global searching molecular dynamics) generate several possible candidates rather then pointing to a single model. Herein we present a new approach to select among candidate models based on the general hypothesis that silent amino acid substitutions, present in variants identified from evolutionary conservation data or mutagenesis analysis, do not affect the stability of a native structure but may destabilize the non‐native structures also found. The proof of this hypothesis has been tested on the α‐helical transmembrane domains of two homodimers, human glycophorin A and human CD3‐ζ, a component of the T‐cell receptor. For both proteins, only one structure was identified using all the variants. For glycophorin A, this structure is virtually identical to the structure determined experimentally by NMR. We present a model for the transmembrane domain of CD3‐ζ that is consistent with predictions based on mutagenesis, homology modeling, and the presence of a disulfide bond. Our experiments suggest that this method allows the prediction of transmembrane domain structure based only on widely available evolutionary conservation data. Proteins 2001;44:370–375. © 2001 Wiley‐Liss, Inc.
Lactones: Part 11. Feeding‐deterrent activity of some bi‐ and tricyclic terpenoid lactones
Authors: Paruch Edyta , Nawrot Jan , Wawrzeńczyk Czeslaw
Published: August 2002

The feeding‐deterrent activities of thirteen synthetic terpenoid lactones, including isomeric bicyclic γ‐spirolactones with the limonene system and tricyclic γ‐lactones with the pinane system, were determined towards three storage pest insects: the adults of Sitophilus granarius, the adults and larvae of Tribolium confusum and the larvae of Trogoderma granarium. The configuration of chiral centres, as well as the presence of additional functional groups (double bond, iodine and hydroxy group) are important for antifeeding activity.

© 2001 Society of Chemical Industry
Effect of temperature, organic amendment rate and moisture content on the degradation of 1,3‐dichloropropene in soil
Authors: Dungan Robert S , Gan Jianying , Yates Scott R
Published: August 2002

1,3‐Dichloropropene (1,3‐D), which consists of two isomers, (Z)‐ and (E)‐1,3‐D, is considered to be a viable alternative to methyl bromide, but atmospheric emission of 1,3‐D is often associated with deterioration of air quality. To minimize environmental impacts of 1,3‐D, emission control strategies are in need of investigation. One approach to reduce 1,3‐D emissions is to accelerate its degradation by incorporating organic amendments into the soil surface. In this study, we investigated the ability of four organic amendments to enhance the rate of degradation of (Z)‐ and (E)‐1,3‐D in a sandy loam soil. Degradation of (Z)‐ and (E)‐1,3‐D was well described by first‐order kinetics, and rates of degradation for the two isomers were similar. Composted steer manure (SM) was the most reactive of the organic amendments tested. The half‐life of both the (Z)‐ and (E)‐isomers in unamended soil at 20 °C was 6.3 days; those in 5% SM‐amended soil were 1.8 and 1.9 days, respectively. At 40 °C, the half‐life of both isomers in 5% SM‐amended soil was 0.5 day. Activation energy values for amended soil at 2, 5 and 10% SM were 56.5, 53.4 and 64.5 kJ mol−1, respectively. At 20 °C, the contribution of degradation from biological mechanisms was largest in soil amended with SM, but chemical mechanisms still accounted for more than 58% of the (Z)‐ and (E)‐1,3‐D degradation. The effect of temperature and amendment rate upon degradation should be considered when describing the fate and transport of 1,3‐D isomers in soil. Use of organic soil amendments appears to be a promising method to enhance fumigant degradation and reduce volatile emissions.

Published in 2001 for SCI by John Wiley & Sons, Ltd
Solid phase synthesis of hydrophobic difficult sequence peptides on BDDMA‐PS support
Authors: Ajikumar P. K. , Devaky K. S.
Published: August 2002

This article illustrates the successful and efficient solid phase assembly of hydrophobic difficult sequence peptides following both t‐Boc and Fmoc chemistry. The peptides were synthesized on an optimized 1,4‐butanediol dimethacrylate‐crosslinked polystyrene support (BDDMA‐PS). Four difficult sequence test peptides, VAVAG, VIVIG, QVGQVELG and VQAAIDYING, were synthesized in relatively good yield and purity without any aggregation problems. The peptides were assembled on chloromethylated and 4‐hydroxymethylphenoxymethyl (HMP) BDDMA‐PS resins. The peptides were fabricated using Boc amino acid 1‐hydroxybenzotriazolyl and Fmoc amino acid pentafluorophenyl active esters in coupling reactions. The peptides after synthesis were cleaved from the polymeric support by exposing the peptidyl resin to 90% trifluroacetic acid/5% thioanisole/5% EDT mixture. The HPLC and MALDI TOF MS studies of the peptides revealed the high homogeneity of the synthesized peptides. Chloromethylated resin having a functional group loading of 1.14 mmol Cl/g was used for the synthesis. The yield and homogeneity of these peptides synthesized using the new support were high when compared with the conventional DVB‐PS resin. Copyright © 2001 European Peptide Society and John Wiley & Sons, Ltd.
Identification of single amino acid residues essential for the binding of lipopolysaccharide (LPS) to LPS binding protein (LBP) residues 86–99 by using an Ala‐scanning library
Authors: Reyes O. , Vallespi M. G. , Garay H. E. , Cruz L. J. , González L. J. , Chinea G. , Buurman W. , Araña M. J.
Published: August 2002

Lipopolysaccharide binding protein (LBP) is a 60 kDa acute phase glycoprotein capable of binding to LPS of Gram‐negative bacteria and facilitating its interaction with cellular receptors. This process is thought to be of great importance in systemic inflammatory reactions such as septic shock. A peptide corresponding to residues 86–99 of human LBP (LBP86–99) has been reported to bind specifically with high affinity the lipid A moiety of LPS and to inhibit the interaction of LPS with LBP. We identified essential amino acids in LBP86–99 for binding to LPS by using a peptide library corresponding to the Ala‐scanning of human LBP residues 86–99. Amino acids Trp91 and Lys92 were indispensable for peptide–LPS interaction and inhibition of LBP–LPS binding. In addition, several alanine‐substituted synthetic LBP‐derived peptides inhibited LPS–LBP interaction. Substitution of amino acids Arg94, Lys95 and Phe98 by Ala increased the inhibitory effect. The mutant Lys95 was the most active in blocking LPS binding to LBP. These findings emphasize the importance of single amino acids in the LPS binding capacity of small peptides and may contribute to the development of new drugs for use in the treatment of Gram‐negative bacterial sepsis. Copyright © 2002 European Peptide Society and John Wiley & Sons, Ltd.
A comparison of three‐ and four‐helix bundle TASP molecules
Authors: Causton Ashley S. , Sherman John C.
Published: August 2002

We have designed, synthesized and characterized three‐ and four‐helix bundle template‐assembled synthetic proteins (TASPs). The TASPs were synthesized using disulphide bonds between the peptides and either the cyclotribenzylene (CTB) template, or the cavitand (BOWL) template, to form the three‐ and four helix bundles, respectively. The TASPs were constructed using peptides that were linked via their N‐termini (peptide CGGGEELLKKXEELLKKG, where X = L, I, Nle or V), or via their C‐termini (peptide GEELLKKLEELLKKGGGC). Each TASP was assayed for its structure, stability, ‘native‐like’ characteristics and whether it was a monomer in solution. All TASPs were found to be highly helical, and highly resistant to chemical denaturation using guanidine hydrochloride (GnHCl). Analysis of the GnHCl‐induced unfolding curves of the different TASPs demonstrated stability differences based on the number of helices in the bundle, the end of the helix that was attached to the template, and the identity of the core amino acid. The TASPs all had molten‐globule structure, which is (generally) consistent with a degenerate sequence in the core. The four‐helix bundle TASPs appeared to be monomers in solution, whereas there is some evidence that the three‐helix bundle TASPs are weakly self‐associating. Copyright © 2002 European Peptide Society and John Wiley & Sons, Ltd.
Peptoid residues and β‐turn formation
Authors: Rainaldi Mario , Moretto Vittorio , Crisma Marco , Peggion Evaristo , Mammi Stefano , Toniolo Claudio , Cavicchioni Giorgio
Published: August 2002

A set of terminally protected tripeptoids containing a residue of either N‐methylglycine or N‐isobutylglycine in position i + 1/i + 2 were synthesized and tested for intramolecularly H‐bonded β‐turn formation. By exploiting FT‐IR absorption and 1H NMR techniques, their folding tendencies were compared with those of a variety of reference peptides. The amount of β‐turn induction and the relative extent of the various types of intramolecularly H‐bonded β‐turn conformers were determined in chloroform solution. Copyright © 2002 European Peptide Society and John Wiley & Sons, Ltd.
Antiinflammatory and antioxidant property of saponins of tea [Camellia sinensis (L) O. Kuntze] root extract
Authors: Sur P. , Chaudhuri T. , Vedasiromoni J. R. , Gomes A. , Ganguly D. K.
Published: August 2002

Two groups of saponins, TS‐1 and TS‐2, isolated from tea root extract (TRE) were tested for antiinflammatory and in vitro antioxidant activity. Both TS‐1 and TS‐2 inhibited carrageenan‐induced paw oedema in rats. The antioxidant activity of these compounds was evaluated using the xanthine–xanthine oxidase system. The study indicated that the previously observed antitumour activity of TRE might be mediated through scavenging of free radicals by saponins and their antiinflammatory activity. Copyright © 2001 John Wiley & Sons, Ltd.
In vitro antileishmanial activity of three saponins isolated from ivy, α‐hederin, β‐hederin and hederacolchiside A1, in association with pentamidine and amphotericin B
Authors: Ridoux O. , Di Giorgio C. , Delmas F. , Elias R. , Mshvildadze V. , Dekanosidze G. , Kemertelidze E. , Balansard G. , Timon‐David P.
Published: August 2002

The in vitro antileishmanial activity of three saponins isolated from ivy, α‐hederin, β‐hederin and hederacolchiside A1, was investigated on parasites of the species Leishmania mexicana, in their promastigote and amastigote forms compared with their toxicity versus human monocytes. The results showed that saponins exhibited a strong antiproliferative activity on all stages of development of the parasite but demonstrated a strong toxicity versus human cells. Association of subtoxic concentrations of saponins with antileishmanial drugs such as pentamidine and amphotericin B demonstrated that saponins could enhance the efficiency of conventional drugs on both the promastigote and the amastigote stages of development of the parasite. The results demonstrated moreover that the action of saponins on promastigote membrane was cumulative with those of amphotericin B. Copyright © 2001 John Wiley & Sons, Ltd.
Spasmolytic activity of Toddalia asiatica var. Floribunda
Authors: Lakshmi V. , Kapoor S. , Pandey K. , Patnaik (Late) G. K.
Published: August 2002

The spasmolytic activity of the aerial parts of Toddalia asiatica var. floribunda (family Rutaceae) was evaluated. The ethanol extract exhibited significant spasmolytic activity and was then partitioned into five fractions. The activity was found to be concentrated only in the hexane and chloroform fractions. This activity was shown not to be due to the coumarins, toddalolactone and toddanone, as was previously thought. Copyright © 2002 John Wiley & Sons, Ltd.
Cytochrome P450nor: A nitric oxide reductase—Structure, spectra, and mechanism
Authors: Harris Danni L.
Published: August 2002

The present study characterizes key proposed intermediates and reaction pathway steps in the enzymatic cycle of cytochrome P450nor, a nitric oxide reductase. This unusual P450, with reductase rather than monoxygenase function, catalyzes the conversion of •NO to N2O, an important detoxification step in the global nitrogen cycle. Density functional theoretical (DFT) and semiempirical INDO/ROHF/CI quantum chemical characterization of the putative species in the enzymatic cycle have been made and direct comparisons made with published experimental spectral and structural data. The computed INDO/ROHF‐CIS spectra of the NO bound heme species indicate a previously reported experimental transient electronic spectrum to be due the NO bound reduced ferrous heme species. The identity of the active heme species in the P450nor mechanism is unknown and may be either a nitrogen (FeN) N‐ferryl analogue of the oxyferryl/compound I P450 species or the NO bound reduced ferrous heme species. Formation of products from either requires the addition of two protons and a second •NO to the NO bound reduced ferrous heme form to form N2O, water, and resting state heme products. The mechanism of proton transfer to the NO bound reduced ferrous NO species is assessed and contrasted with that discovered for the reduced oxyferrous heme species of cytochrome P450 monoxygenases. DFT reaction pathways studies are reported for the addition of •NO to the N‐ferryl species and indicate it to be a competent active species forming N2O via an exothermic, barrierless process. © 2002 John Wiley & Sons, Inc. Int J Quantum Chem, 2002
Relativistic effects in the optical response of HgSe by time‐dependent density functionals theory
Authors: de Boeij P. L. , Kootstra F. , Snijders J. G.
Published: August 2002

We treat the dominant relativistic effects in the optical response properties of mercury selenide using time‐dependent density functional theory (TDDFT). The scalar relativistic effects have been included within the zeroth‐order regular approximation (ZORA) in both the ground‐state DFT calculations and in the time‐dependent response calculations. Within this approximation the HgSe crystal is found to be a semimetal. In a previous study [J Chem Phys 2001, 114, 1860] we have shown that TDDFT/ZORA can be applied successfully to narrow‐gap semiconductors, such as indium antimonide, that become semimetallic within the local density approximation when scalar relativistic effects are included. Results are given for the band structure, the static dielectric constant ϵ∞, and the dielectric function ϵ(ω) of HgSe, and these results are compared with the similar ones for InSb. We find considerably improved results for the dielectric function of HgSe when relativistic effects are included. © 2001 John Wiley & Sons, Inc. Int J Quantum Chem, 2001
Development of a method based on accelerated solvent extraction and liquid chromatography/mass spectrometry for determination of arylphenoxypropionic herbicides in soil
Authors: Marchese Stefano , Perret Daniela , Gentili Alessandra , Curini Roberta , Marino Aldo
Published: August 2002

A sensitive and specific analytical procedure for determining arylphenoxypropionic herbicides in soil samples, using Ionspray ionization (ISI) liquid chromatography/mass spectrometry (LC/MS), is presented. Arylphenoxypropionic acids are a new class of herbicides used for selective removal of most grass species from any non‐grass crop, commercialized as herbicide esters. Previous studies have shown that the esters undergo fast hydrolysis in the presence of vegetable tissues and soil bacteria, yelding the corresponding free acid. The feasibility of rapidly extracting arylphenoxypropionic herbicides from soil by accelerated solvent extraction (ASE) techniques was evaluated. Four different soil samples were fortified with target compounds at levels of 5 and 20 ng/g by following a procedure able to mimic weathered soils. Herbicides were extracted by a methanol/water (80:20 v/v) solution (0.12 M) of NaCl at 90 °C. After clean‐up using graphitized carbon black (GCB) as absorbent, the extract was analyzed by HPLC/ISI‐MS. The effect of concentration of acid in the mobile phase on the response of ISI‐MS was investigated. The effects of varying the orifice plate voltage on the production of diagnostic fragment ions, and on the response of the MS detector, were also investigated. The ISI‐MS response was linearly related to the amounts of analytes injected between 1 and 200 ng. The limit of detection (signal‐to‐noise ratio = 3) of the method for the pesticides in soil samples was estimated to be less than 1 ng/g. Copyright © 2001 John Wiley & Sons, Ltd.
On the maximum number of Hamiltonian paths in tournaments
Authors: Adler Ilan , Alon Noga , Ross Sheldon M.
Published: August 2002

By using the probabilistic method, we show that the maximum number of directed Hamiltonian paths in a complete directed graph with n vertices is at least (e−o(1)) (n!/2n−1). © 2001 John Wiley & Sons, Inc. Random Struct. Alg., 18: 291–296, 2001
GPRS random access channel performance over the Geostationary Mobile Satellite Standard
Authors: Voce Daniel A.
Published: August 2002

The performance of the General Packet Radio Service (GPRS) random access channel as applied to the newly proposed Geostationary Mobile Satellite Standard (GMSS) is analysed. This standard adapts the GSM air interface to a geostationary satellite network. The channel is studied using analytical techniques. Copyright © 2001 John Wiley & Sons, Ltd.
Multidirectional associative memory with a hidden layer
Authors: Kobayashi Masaki , Hattori Motonobu , Yamazaki Haruaki
Published: August 2002

MAM (Multidirectional Associative Memory) is an extended BAM (Bidirectional Associative Memory), and an associative memory model which can deal with multiple associations. If the training set has common terms, the conventional MAM often recalls the convolutional patterns. IMAM (Improved Multidirectional Associative Memory) can store them, but the structure is complex and the storage capacity is extremely small because it must use correlation matrix. In this paper, we propose a MAM with a hidden layer and its learning method. The structure is as simple as MAM and can store the training set which includes common terms. By computer simulation, we show the storage capacity is far larger than correlation learning and it is robust against noise. © 2002 Wiley Periodicals, Inc. Syst Comp Jpn, 33(6): 1–9, 2002; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/scj.10105
Statistical filter for multiple test noise on fMRI
Authors: Takada Takahiro , Hasegawa Takemitsu , Ogura Hisakazu , Tanaka Masato , Yamada Hiroki , Komuro Hiroyuki , Ishii Yasushi
Published: August 2002

EPI‐based fMRI technology, with a capability for high‐speed imaging, is expected to make possible the analysis of brain activation states in vivo. However, actual functional images acquired by fMRI contain much noise, which is a problem for detailed analysis, and improvement of image quality remains an important task. Such noise in fMRI images includes not only components related to fluctuations of signal intensity, but also those related to image processing. In functional brain images acquired by fMRI, the signals are weak; although activated states can be detected at the pixel level, the activation images thus obtained include test errors caused by multiple testing. Such errors might be reduced to some extent by the usual noise filters, but in reality statistical filters using statistical properties of noise should be employed. The statistical filter proposed in this study uses the binomial distribution to decide whether the activation states in a certain region occur at random or not. The proposed filter is evaluated by computer simulation. In addition, the paper presents the results of applying the filter to brain activation images acquired by fMRI during stimulation by finger tapping. © 2001 Scripta Technica, Syst Comp Jpn, 32(12): 16–24, 2001
A tracking algorithm for extracting ridge lines in three‐dimensional gray images using curvature of four‐dimensional hypersurface
Authors: Hirano Yasushi , Shimizu Akinobu , Hasegawa Jun‐ichi , Toriwaki Jun‐ichiro
Published: August 2002

This paper proposes a thinning algorithm for tracking ridge lines in three‐dimensional (3D) gray images. A characteristic of this algorithm is that input 3D gray images can be used directly without preprocessing such as binarization or separation of background. This algorithm obtains thin lines by tracking ridge lines, starting at points where the intensity has its local maximum. Combinations of three principal curvatures of a 4D hypersurface are used for the condition of continuation of tracking. It has been verified that lines considered to be ridge lines can be extracted when the proposed algorithm is applied to artificial images and real images. © 2001 Scripta Technica, Syst Comp Jpn, 32(12): 25–37, 2001
The source of poor policy: controlling learning drift and premature consensus in human organizations
Authors: Hines Jim , House Jody
Published: August 2002

As system dynamicists, we spend our days finding and patching up faulty policies, giving surprisingly little thought to the origin of these poor decision rules. And yet, if we understood their origin, we might be able to attack the problem of faulty policy at its source. This article presents a theory of policy formation that is consistent with what is known about evolutionary processes and human psychology. The theory is translated into a computer simulation model, which is used to illuminate several “handles” on policy creation. The handles influence two potential failure modes in policy creation: (1) “learning drift”, a process in which people learn unselectively and, hence, learn without improving; and/or (2) “premature consensus”, a process in which managers agree on a policy before the “best” one has emerged. Copyright © 2001 John Wiley & Sons, Ltd.
Toward a synthesis of the resource‐based and dynamic‐capability views of rent creation
Authors: Makadok Richard
Published: August 2002

Two distinct causal mechanisms—resource‐picking and capability‐building—have been proposed in the strategic management literature about how firms create economic rents. Under the resource‐picking mechanism, managers gather information and analysis to outsmart the resource market in picking resources, similar to the way that a mutual fund manager tries to outsmart the stock market in picking stocks. Under the capability‐building mechanism, managers design and construct organizational systems to enhance the productivity of whatever resources the firm acquires. These two rent‐creation mechanisms are certainly not mutually exclusive, and it is likely that firms generally use both of them. It is therefore important to consider the interaction between these two rent‐creation mechanisms: Do they complement each other? Or are they substitutes for each other? In other words, do they enhance each other's value, or detract from each other's value? Answering these questions is a necessary precondition to understanding how firms should allocate their time and effort between these two rent‐creation mechanisms. The present paper develops a basic theoretical model to address these questions, and derives testable hypotheses from the model. The model predicts that the two rent‐creation mechanisms are complementary in some circumstances but substitutes in others. Copyright © 2001 John Wiley & Sons, Ltd.
A reexamination and extension of international strategy–structure theory
Authors: Wolf Joachim , Egelhoff William G.
Published: August 2002

Using a sample of 95 German firms, the study finds general support for the traditional fits of international strategy–structure theory. Employing an information‐processing perspective, the study conceptually and empirically extends existing theory (1) to address strategy–structure fit for various types of matrix structure, and (2) by adding two new elements of international strategy to the existing international strategy–structure model: the level of international transfers and level of foreign R&D. Copyright © 2002 John Wiley & Sons, Ltd.
Analysing, modelling and improving workflow application development processes
Authors: Weske Mathias , Goesmann Thomas , Holten Roland , Striemer Rüdiger
Published: August 2002

The success of workflow projects to a large extent depends on how workflow application development processes are planned, organized and conducted. Based on lessons learned from problems encountered during real‐world workflow projects, this paper presents a development methodology for workflow application development processes, which guides project managers and developers through the complex structure of these processes, aiming at developing more adequate, usable and reliable workflow applications. Copyright © 2001 John Wiley & Sons Ltd
Current status of total mesorectal excision and autonomic nerve preservation in rectal cancer
Authors: Murty Murali , Enker Warren E. , Martz Joseph
Published: August 2002

Two decades have passed since the late 1970s, which witnessed the introduction of total mesorectal excision (TME)‐based operations for rectal cancers on both sides of the Atlantic. Since the introduction of TME, clinical experience has been reported widely in the form of single‐ and multisurgeon reports from wide geographic regions with multiple participants, and from specialty services with narrow focus and high levels of expertise. All of these published results conclude that in comparison with conventionally practiced blunt surgery for rectal cancer, TME‐based (i.e., anatomically correct, sharply performed) operations are associated with significantly lower rates of pelvic (local) recurrences, a significantly higher rate of survival, and significantly lower long‐term morbidity. The latter is accomplished through dramatically higher rates of sphincter preservation, and the preservation of both sexual and urinary functions. Overall, there is a remarkable similarity in the clinical results that have been reported from diverse centers. TME now forms the basis of large randomized clinical trials in which the role of adjuvant therapy is being reexamined. The current status of TME is reviewed, and the authors’ clinical results of a consecutive series of 544 TME‐based operations performed through 1998 are updated. Semin. Surg. Oncol. 19:321–328, 2000. © 2000 Wiley‐Liss, Inc.
3D technologies and products for e‐commerce on the Web
Authors: Sanna Andrea , Montrucchio B.
Published: August 2002

In this paper, A. SANNA and B. MONTRUCCHIO identify and compare different solutions for 3D graphics on the Web. The main available technologies and products are introduced and compared. Copyright © 2002 John Wiley & Sons, Ltd.
Long‐term impairment of anterograde axonal transport along fiber projections originating in the rostral raphe nuclei after treatment with fenfluramine or methylenedioxymethamphetamine
Authors: Callahan Brian T. , Cord Branden J. , Ricaurte George A.
Published: August 2002

To further evaluate the serotonin (5‐HT) neurotoxic potential of substituted amphetamines, we used tritiated proline to examine anterograde transport along ascending axonal projections originating in the rostral raphe nuclei of animals treated 3 weeks previously with (±)fenfluramine (FEN, 10 mg/kg, every 2 h × 4 injections; i.p.) or (±)3,4‐methylenedioxymethamphetamine (MDMA, 20 mg/kg, twice daily for 4 days; s.c.). The documented 5‐HT neurotoxin, 5,7‐dihydroxytryptamine (5,7‐DHT, 75 μg; ICV; 30 min after pretreatment with pargyline, 50 mg/kg; i.p., and desipramine 25 mg/kg; i.p.), served as a positive control. Along with anterograde axonal transport, we measured two 5‐HT axonal markers, 5‐HT and 5‐hydroxyindoleacetic acid (5‐HIAA). Prior treatment with FEN or MDMA led to marked reductions in anterograde transport of labeled material to various forebrain regions known to receive 5‐HT innervation. These reductions were associated with lasting decrements in 5‐HT axonal markers. In general, decreases in axonal transport were less pronounced than those in 5‐HT and 5‐HIAA. However, identical changes were observed after 5,7‐DHT. These results further indicate that FEN and MDMA, like 5,7‐DHT, are 5‐HT neurotoxins. Synapse 40:113–121, 2001. © 2001 Wiley‐Liss, Inc.
Vesicular acetylcholine transporter in the rat nucleus accumbens shell: Subcellular distribution and association with μ‐opioid receptors
Authors: Svingos Adena L. , Colago Eric E.O. , Pickel Virginia M.
Published: August 2002

Cholinergic interneurons in the nucleus accumbens shell (AcbSh) are implicated in the reinforcing behaviors that develop in response to opiates active at μ‐opioid receptors (MOR). We examined the electron microscopic immunocytochemical localization of the vesicular acetylcholine transporter (VAChT) and MOR to determine the functional sites for storage and release of acetylcholine (ACh), and potential interactions involving MOR in this region of rat brain. VAChT was primarily localized to membranes of small synaptic vesicles in axon terminals. Less than 10% of the VAChT‐labeled terminals were MOR‐immunoreactive. In contrast, 35% of the cholinergic terminals formed symmetric or punctate synapses with dendrites showing an extrasynaptic plasmalemmal distribution of MOR. Membranes of tubulovesicles in other selective dendrites were also VAChT‐labeled, and almost half of these dendrites displayed plasmalemmal MOR immunoreactivity. The VAChT‐labeled dendritic tubulovesicles often apposed unlabeled axon terminals that formed symmetric synapses. Our results indicate that in the AcbSh MOR agonists can modulate the release of ACh from vesicular storage sites in axon terminals as well as in dendrites where the released ACh may serve an autoregulatory function involving inhibitory afferents. These results also suggest, however, that many of the dendrites of spiny projection neurons in the AcbSh are dually influenced by ACh and opiates active at MOR, thus providing a cellular substrate for ACh in the reinforcement of opiates. Synapse 40:184–192, 2001. © 2001 Wiley‐Liss, Inc.
Selection of technical risk responses for efficient contingencies
Authors: Kujawski Edouard
Published: August 2002

The primary goal of good project risk management should be to successfully deliver projects for the lowest cost at an acceptable level of risk. This requires the systematic development and implementation of a set of Risk Response Actions (RRAs) that achieves the lowest total project cost for a given probability of success while meeting technical performance and schedule. We refer to this set as the “efficient RRA set.” This work presents a practical and mathematically sound approach for determining the efficient RRA set. It builds on some of Markowitz's portfolio selection principles and introduces several conceptual and modeling differences to properly treat project technical risks. The set of RRAs is treated as whole and not just individual risks. The efficient RRA set is determined based on “Outcome Cost vs. Probability of Success.” The risks and RRAs are characterized using scenarios, decision trees, and cumulative probability distributions. The analysis provides information that enables decision‐makers to select the efficient RRA set that explicitly takes their attitude toward project risk into account. Decision‐makers should find it both useful and practical for sound decision‐making under uncertainty/risk and efficiently optimizing project success. The computations are readily performed using commercially available Monte Carlo simulation tools. The approach is detailed using a realistic but simplified case of a project with two technical risks. © 2002 Wiley Periodicals, Inc. Syst Eng 5, 194–212, 2002
The systems engineering started in the middle process: A consensus of systems engineers and project managers
Authors: Bahill A. Terry , Briggs Clark
Published: August 2002

The systems engineering process often begins somewhere in the middle of a project. Naturally, the systems engineering process should be different for a project where systems engineering starts in the middle versus a project where it starts at the beginning of the project. This article presents a consensus of senior systems engineers and project managers at the Idaho National Engineering and Environmental Laboratory and Raytheon Missile Systems about how systems engineering is done when it starts in the middle of a project. © 2001 John Wiley & Sons, Inc. Syst Eng 4: 156–167, 2001
Using a requirement management tool for verification management
Authors: Hamann R. J. , Oort M. J. A.
Published: August 2002

This article discusses the experiences at a medium‐sized space industry with the application of both custom‐made and commercial tools for requirements and verification management. It lists the advantages and disadvantages of the different implementations and concludes that none of them are fully satisfactory. Possible reasons for this outcome are suggested. © 2001 John Wiley & Sons, Inc. Syst Eng 4: 169–178, 2001
Assessment of DNA damage in spleen, bone marrow, and peripheral blood from malnourished rats by single cell gel electrophoresis assay
Authors: Cortés Edith , González Cristina , Betancourt Miguel , Ortiz Rocío
Published: August 2002

Severe malnutrition is widely distributed throughout the world and exhibits a high prevalence in developing countries. Experimental malnutrition models have been useful to study the effects of malnutrition at early ages. The purpose of this study was to determine if severe malnutrition induced during lactation in rats increases DNA damage in spleen, peripheral blood, and bone marrow cells, as well as in isolated lymphocytes or lymphoid cells from the same tissues. These cells were obtained from malnourished rats at weaning (21 days of age). DNA damage was estimated by using the alkaline single cell electrophoresis assay. The results obtained in this study indicate that malnutrition is associated with a significant increase in DNA damage in all cell types that were studied in malnourished rats. The analysis of the length of DNA migration and dispersion coefficient showed that some cell types were more susceptible to DNA damage related with malnutrition. The damage observed could be due to the deficiency of several essential nutrients required for protein synthesis that are associated with DNA integrity, impaired DNA repair mechanisms, and/or to the unavailability of molecules necessary to protect the cells against DNA oxidative damage. This damage may produce negative effects for the further development of the organism, since bone marrow is the main site of hematopoiesis and spleen is an important lymphopoietic organ. Also, the increased level of DNA damage in peripheral blood lymphocytes and leukocytes could be related to negative effects such as a deficient immune response. Teratogenesis Carcinog. Mutagen. 21:231–247, 2001. © 2001 Wiley‐Liss, Inc.