bluuebunny/crossref_metadata_2025 huggingface dataset:
Chronic lung disease of the newborn is not associated with Ureaplasma urealyticum
Authors: Ollikainen Jukka , Korppi Matti , Heiskanen‐Kosma Tarja , Heinonen Kirsti
Published: August 2002

To clarify the association of Ureaplasma urealyticum infection with chronic lung disease of the newborn 145 preterm infants less than 34 weeks of gestation were examined. The infants were enrolled during two separate periods. The presence of U. urealyticum was studied by obtaining endotracheal culture samples and blood samples; if either of these samples grew the organism, the child was regarded as having U. urealyticum infection. Infection with U. urealyticum was detected in 33%, and chronic lung disease (defined as the need for oxygen, and typical chest radiograph at 28 days of age) in 43% of infants. The development of chronic lung disease was not associated with the presence of U. urealyticum.

Our results suggest only a minor indirect role for U. urealyticum in the development of chronic lung disease of the newborn. Pediatr Pulmonol. 2001; 32:303–307. © 2001 Wiley‐Liss, Inc.
Endothelin‐1 production by prostate cancer cell lines is up‐regulated by factors involved in cancer progression and down‐regulated by androgens
Authors: Granchi Simone , Brocchi Sandro , Bonaccorsi Lorella , Baldi Elisabetta , Vinci Maria Cristina , Forti Gianni , Serio Mario , Maggi Mario
Published: August 2002

Background

Recent data demonstrate that endothelin‐1 (ET‐1) concentration increases in plasma of men with advanced, hormone‐refractory prostate adenocarcinoma. In addition, ET‐1 is involved in osteblastic remodelling and new bone formation, suggesting a role for this vasoactive peptide in the metastatic progression of prostate cancer to the bone.

Methods

We investigated the regulation of ET‐1 expression in androgen‐sensitive and insensitive prostate cancer cell lines by androgens and several factors involved in progression of prostate cancer (EGF) and bone remodelling (TGFβ‐1, IL1‐α and IGF‐1).

Results

Northern analysis and radio immunoassay demonstrated that all the ET‐1 pathways are tuned off in the androgen‐sensitive LNCaP cell line when compared to the androgen‐insensitive PC‐3 and DU145. In PC‐3 cells transfected with a full‐length androgen receptor expression vector (PC‐3‐AR), treatment with androgens reduced gene expression and secretion of ET‐1 without affecting the gene expression of ET‐3. Collectively, these data support a role for androgens in the regulation of ET‐1 production by prostate adenocarcinoma cells. In PC‐3 and DU145 cells, ET‐1 gene expression and secretion were up‐regulated by TGFβ‐1, EGF and IL1‐α, whereas IGF‐1 was ineffective. Conversely, none of the treatments affected ECE‐1 or ET‐3 gene expression.

Conclusions

In conclusion, ET‐1 production by prostate adenocarcinoma cells is down‐regulated by androgens and up‐regulated by factors involved in tumour progression indicating a role for this peptide in the biology of prostate cancer. In view of the role exerted by ET‐1 in the process of bone metastasis, our data suggest the use of ET‐1 receptor antagonists in the treatment of advanced prostate cancer. Prostate 49:267–277, 2001. © 2001 Wiley‐Liss, Inc.
Expression of peroxisome proliferator‐activated receptor (PPAR) in human prostate cancer
Authors: Segawa Yoshihiro , Yoshimura Rikio , Hase Taro , Nakatani Tatsuya , Wada Seiji , Kawahito Yutaka , Kishimoto Taketoshi , Sano Hajime
Published: August 2002

BACKGROUND

Recent studies have demonstrated that peroxisome proliferator activator‐receptors (PPAR)‐γ is expressed in some cancer cells such as breast, lung, and gastric cancer, and its ligand induces growth arrest of these cancer cells through apoptosis. However, the expression and localization of PPARs in prostate have not been examined. In this study, PPARs expression was investigated in human prostate cancer (PC), prostatic intraepithelial neoplasia (PIN), benign prostatic hyperplasia (BPH), and normal prostate (NP) tissues.

METHODS

Tumor specimens were obtained from 156 patients with PC, 15 with PIN, 20 with BPH, and 12 patients with NP tissues. The expressions were investigated by RT‐PCR and immunohistochemical methods.

RESULTS

Immunoreactive PPAR‐α and ‐β were significantly apparent in PC tissues. Marked expressions of PPAR‐α and ‐β were also detected in PIN, BPH, and NP groups. However, very weak or no expression of immunoreactive PPAR‐γ was found in BPH and NP cases. In contrast, we found significant expression of immunoreactive PPAR‐γ in cancer cells in PC group and in PIN group.

CONCLUSIONS

Our results demonstrated that PPAR‐γ is induced in PC, and suggest that PPAR‐γ ligands may mediate its own potent antiproliferative effect against PC cells through differentiation. Prostate 51: 108–116, 2002. © 2002 Wiley‐Liss, Inc.
Curcumin enhances cytotoxicity of chemotherapeutic agents in prostate cancer cells by inducing p21WAF1/CIP1 and C/EBPβ expressions and suppressing NF‐κB activation
Authors: Hour Tzyh‐Chyuan , Chen Jun , Huang Chao‐Yuan , Guan Jing‐Yi , Lu Shiu‐Hui , Pu Yeong‐Shiau
Published: August 2002

BACKGROUND

The modulatory effects and molecular mechanisms of curcumin (CCM) on the cytotoxicity of chemotherapeutic agents to prostate cancer cells were explored.

METHODS

The combined effects of CCM and chemotherapeutic agents were examined by three different administration schedules (one concurrent and two sequential treatments) in two androgen‐independent prostate cancer (AIPC) cells (PC‐3 and DU145). Alteration of cell cycle progression, protein levels, and transcriptional activation in PC‐3 cells were assayed by flow cytometry, Western blotting, and gel shift assay, respectively.

RESULTS

The combined effects of CCM → chemotherapeutic agent schedule showed the greatest synergistic cytotoxicity when compared to the other two schedules in both cells. CCM induced a significant G1 arrest in PC‐3, which may be mediated by the induction of p21WAF1/CIP1 and C/EBPβ. Moreover, CCM was able to inhibit both the constitutional and TNF‐α‐induced NF‐κB activation in a time‐dependent manner.

CONCLUSIONS

The incorporation of CCM into cytotoxic therapies may be a promising strategy for the treatment of AIPC. Prostate 51: 211–218, 2002. © 2002 Wiley‐Liss, Inc.
Molecular dynamics study of a hyperthermophilic and a mesophilic rubredoxin
Authors: Grottesi Alessandro , Ceruso Marc‐Antoine , Colosimo Alfredo , Di Nola Alfredo
Published: August 2002

In recent years, increased interest in the origin of protein thermal stability has gained attention both for its possible role in understanding the forces governing the folding of a protein and for the design of new highly stable engineered biocatalysts. To study the origin of thermostability, we have performed molecular dynamics simulations of two rubredoxins, from the mesophile Clostridium pasteurianum and from the hyperthermophile Pyrococcus furiosus. The simulations were carried out at two temperatures, 300 and 373 K, for each molecule. The length of the simulations was within the range of 6–7.2 ns. The rubredoxin from the hyperthermophilic organism was more flexible than its mesophilic counterpart at both temperatures; however, the overall flexibility of both molecules at their optimal growth temperature was the same, despite 59% sequence homology. The conformational space sampled by both molecules was larger at 300 K than at 373 K. The essential dynamics analysis showed that the principal overall motions of the two molecules are significantly different. On the contrary, each molecule showed similar directions of motion at both temperatures. Proteins 2002;46:287–294. © 2002 Wiley‐Liss, Inc.
Probing the structure of the warfarin‐binding site on human serum albumin using site‐directed mutagenesis
Authors: Petersen Charles E. , Ha Chung‐Eun , Curry Stephen , Bhagavan Nadhipuram V.
Published: August 2002

The binding of warfarin to the following human serum albumin (HSA) mutants was examined: K195M, K199M, F211V, W214L, R218M, R222M, H242V, and R257M. Warfarin bound to human serum albumin (HSA) exhibits an intrinsic fluorescence that is approximately 10‐fold greater than the corresponding signal for warfarin in aqueous solution. This property of the warfarin/HSA complex has been widely used to determine the dissociation constant for the interaction. In the present study, such a technique was used to show that specific substitutions in subdomain 2A altered the affinity of HSA for warfarin. The fluorescence of warfarin/mutant HSA complexes varied widely from the fluorescence of the warfarin/wild‐type HSA complex at pH = 7.4, suggesting changes in the structure of the complex resulting from specific substitutions. The fluorescence of the warfarin/wild‐type HSA complex increases about twofold as the pH is increased from 6.0 to 9.0 due to the neutral‐to‐base (N–B) transition, a conformational change that occurs in HSA as a function of pH. Changes in the fluorescence of warfarin/mutant HSA complexes as a function of pH suggests novel behavior for most HSA species examined. For the HSA mutants F211V and H242V, the midpoint of the N–B transition shifts from a wild‐type pH of 7.8 to a pH value of 7.1–7.2. Proteins 2002;47:116–125. © 2002 Wiley‐Liss, Inc.
An appraisal of methods for measurement of pesticide transformation in the groundwater zone
Authors: Leistra Minze , Smelt Johan H
Published: August 2002

Laboratory and field studies show that pesticides may be transformed in the groundwater zone. Possible reaction mechanisms are chemical hydrolysis, catalytic reduction and aerobic or anaerobic microbial transformation. Transformation in the groundwater zone can be an important element in the advanced evaluation of the potential risk arising from a pesticide in the public drinking water supply. However, rate and pathway of transformation can show large differences, depending on the bio‐geochemical conditions in the groundwater zone. Knowledge of the reaction mechanisms and the effect of aquifer conditions would allow vulnerable and low‐vulnerable application areas for a pesticide to be delimited. An outline is given of possible approaches to quantifying these transformation processes and using the results in registration procedures, especially in the EU and its member states. Furthermore, areas where there is need for continued research and better understanding are highlighted.

© 2001 Society of Chemical Industry
Is attract‐and‐kill technology potent against insecticide‐resistant Lepidoptera?
Authors: Poullot Delphine , Beslay Dominique , Bouvier Jean‐Charles , Sauphanor Benoît
Published: August 2002

Attract‐and‐kill techniques, associating an attractant and a contact insecticide in a sticky formulation, are a new way of controlling Lepidopteran pests. Insecticide resistance may, however, limit the effectiveness and even the attractiveness of such formulations where resistance pleiotropic effects influence pheromone perception. We have tested this hypothesis on resistant codling moths Cydia pomonella (L) using a commercial formulation containing (E,E)‐8,10‐dodecadien‐1‐ol (codlemone), the major component of the sex pheromone, as an attractant and permethrin as toxicant. We first compared the attractiveness of codlemone in a wind tunnel and the contact toxicity of pyrethroids on males of one susceptible and of three strains selected for resistance to diflubenzuron, deltamethrin and azinphos‐methyl. The dose‐response relationships of males of susceptible and resistant strains to codlemone did not differ significantly. The deltamethrin‐selected strain was the most resistant to pyrethroids, exhibiting 138‐, 25‐ and 18‐fold resistance ratios to deltamethrin, cypermethrin and permethrin, respectively. The efficiency of the attracticide formulation, applied successively on filter paper support, glass support and wood support, was estimated by recording the mortality delay of males after natural contact with the formulation in the wind tunnel. The deltamethrin‐and diflubenzuron‐resistant strains were significantly less affected than the susceptible strain by contact with the attracticide on the wooden support, exhibiting 58‐ and 2.3‐fold greater LT50 ratios, respectively. Mortality of deltamethrin‐resistant moths did not exceed 40% after 48 h. The LT50 value was significantly greater on filter paper support than on the two other supports. Surprisingly, the LT50 ratio of the deltamethrin‐resistant strain was markedly higher on filter paper support (1021‐fold), which was more absorbent, than on the glass support (31‐fold). No sublethal effects in terms of pheromone response, mating or fecundity occurred in moths surviving contact with the attracticide. Choice of insecticides in attracticide formulations will be influenced by the resistance background of the target pests. Principles of insecticide resistance management may also be applied to attract‐and‐kill technology by alternating with other insecticides or control methods.

© 2001 Society of Chemical Industry
Transferability of fracture mechanics parameters to fracture performance evaluation of welds with mismatching
Authors: Toyoda Masao
Published: August 2002

In order to evaluate fracture performance of steel welded structures, the fracture mechanics approach has been adopted. However, it has frequently been pointed out that conventional fracture mechanics parameters are not necessarily applicable to all cases. This inconsistency is due to the difference of stress–strain behaviour depending on plastic constraints in the vicinity of a crack tip between the fracture toughness testing specimen and the practical structures. Accordingly, the transferability of the fracture‐controlling parameter and a new appropriate procedure is discussed.

In the welded joint, moreover, the mismatching of metallurgical/mechanical properties inevitably exists. Mismatching in strength also results in considerable change in plastic constraints. It is very important that the combined consideration of both strength mismatching and transferability for critical assessment of the structural integrity with regard to the unstable fracture of steel welded structures.

The present paper summarizes the recent activities on transferability of fracture toughness data to fracture assessment in structural welded joints, with particular reference to mechanical heterogeneity observed in welded joints.
Cytotoxic coumarins and lignans from extracts of the northern prickly ash (Zanthoxylum americanum)
Authors: Ju Yong , Still Cecil C. , Sacalis John N. , Li Jiangang , Ho Chi‐Tang
Published: August 2002

Four pyranocoumarins; dipetaline, alloxanthoxyletin, xanthoxyletin and xanthyletin; and two lignans; sesamin and asarinin were isolated from the northern prickly ash, Zanthoxylum americanum. To varying degrees, all inhibited the incorporation of tritiated thymidine into human leukaemia (HL‐60) cells. Dipetaline was the most active with an IC50 of 0.68 ppm, followed by alloxanthoxyletin (1.31 ppm), sesamin (2.71 ppm), asarinin (4.12 ppm), xanthoxyletin (3.48 ppm) and xanthylletin (3.84 ppm). Copyright © 2001 John Wiley & Sons, Ltd.
Garcinia extract inhibits lipid droplet accumulation without affecting adipose conversion in 3T3‐L1 cells
Authors: Hasegawa Noboru
Published: August 2002

Garcinia extract was isolated from the fruit of the Garcinia cambogia and was used as a potential antiobesity agent. In week 3 of culture with insulin, the fat cells exhibited more numerous and larger intracytoplasmic lipid droplets (i.e. 30–40 µm2). When Garcinia extract and insulin were added simultaneously, the accumulation of lipid droplets was inhibited and the peak droplet area shifted to become smaller (10–20 µm2). The activities of glycerophosphate dehydrogenase, a marker of adipose differentiation, were not significantly inhibited by the Garcinia extract. These findings suggest that the Garcinia extract inhibits lipid droplet accumulation in fat cells without affecting adipose conversion. Copyright © 2001 John Wiley & Sons, Ltd.
Antibacterial activity of some Moroccan medicinal plants
Authors: Larhsini M. , Oumoulid L. , Lazrek H.B. , Wataleb S. , Bousaid M. , Bekkouche K. , Jana M.
Published: August 2002

The extracts of 12 plants selected on the basis of the folk‐medicine reports were examined for their antibacterial effects against eight pathogenic bacteria. The n‐butanol extract of Calotropis procera flowers and the aqueous extract of Eugenia caryophyllata proved to be the most effective against the bacteria tested. Copyright © 2001 John Wiley & Sons, Ltd.
An aqueous extract of the green leafy vegetable Ipomoea aquatica is as effective as the oral hypoglycaemic drug tolbutamide in reducing the blood Sugar levels of Wistar rats
Authors: Malalavidhane S. , Wickramasinghe S. M. D. N. , Jansz E. R.
Published: August 2002

This study was undertaken to compare the oral hypoglycaemic activity of an aqueous extract of the green leafy vegetable Ipomoea aquatica (dose equivalent to 3.3 g starting material /kg body weight) with that of the known oral hypoglycaemic drug tolbutamide (15 mg/kg body weight) in glucose challenged Wistar rats (3 g/kg body weight, administered 30 min after the administration of Ipomoea aquatica or tolbutamide). One and half hours after administration of glucose (equivalent to 2 h after administration of plant extract or tolbutamide), the mean blood glucose level of the Ipomoea aquatica treated group was 47.5% lower than that of the control group treated with distilled water. The tolbutamide treated group showed a mean blood glucose level which was only 33.8% lower than that of the control group. However, statistical analysis indicated that the blood glucose levels of the Ipomoea aquatica treated group were not significantly different from that of the tolbutamide treated group. Our results show that the aqueous extract of Ipomoea aquatica is as effectve as tolbutamide in reducing the blood glucose levels of glucose‐challenged Wistar rats. Copyright © 2001 John Wiley & Sons, Ltd.
Antidiarrhoeal activity of the aqueous extract of Terminalia avicennoides roots
Authors: Abdullahi A. L. , Agho M. O. , Amos S. , Gamaniel K. S. , Wambebe C.
Published: August 2002

The antidiarrhoeal effects of the aqueous root extract of Terminalia avicennoides were evaluated in rodents. Studies were carried out on the isolated rabbit jejunum, gastrointestinal motility in vivo and on castor oil‐induced diarrhoea in mice. The results revealed that the extract exhibited a concentration‐dependent inhibition of the spontaneous pendular movement of the isolated rabbit jejunum and attenuated acetylcholine induced contractions. The extract (100, 200 and 400 mg/kg) also caused a dose‐dependent decrease of gastrointestinal transit and markedly protected mice against castor oil‐induced diarrhoea. The intraperitoneal LD50 of the extract was found to be 871.4–917.4 mg/kg in mice (95% confidence). A preliminary phytochemical screening of the aqueous extract of T. avicennoides roots revealed the presence of tannins, saponins and flavonoids. The results obtained showed that the water extract of T. avicennoides roots may contain some biologically active principles that may be active against diarrhoea and this may be the basis for its use traditionally for gastrointestinal disorders. Copyright © 2001 John Wiley & Sons, Ltd.
Effect of a lipopolysaccharide from E. coli on the proliferation of fibroblasts and keratinocytes in vitro
Authors: Yang H. , Kaneko M. , He C. , Hughes M. A. , Cherry G. W.
Published: August 2002

Studies previously conducted in our laboratory have shown that an extract from the leaves of Chromo‐laena odorata is mitogenic for human skin fibroblasts and keratinocytes. However, lipopolysaccharides, sometimes present in plant extracts, can also play a role in cell growth and might have been responsible for or contributed to the mitogenic activity observed. The present study aimed to investigate whether a lipopolysaccharide would have any effect on the proliferation of human fibroblasts and keratinocytes. Cells were seeded in 96‐well plates and concentrations from 0.0 to 5.0 μg/mL of lipopolysaccharide in basal or growth medium were added. Cell growth was determined over a period of 10 days using a colorimetric assay. Lipopolysaccharide at concentrations between 0.05 μg/mL and 0.5 μg/mL in the growth medium significantly stimulated fibroblast proliferation after incubation for more than 6 days. In basal medium, more than 8 days of incubation was needed for significant stimulation of growth. Lipopolysaccharide stimulation of keratinocytes was evident at 0.5 μg/mL by day 3 in basal medium and by day 5 in growth medium. Although the lipopolysaccharide did stimulate cell growth it did so only at higher concentrations than were present in our plant extracts and to a lesser degree. Copyright © 2002 John Wiley & Sons, Ltd.
Effects of Linalool on [3H] MK801 and [3H] Muscimol Binding in Mouse Cortical Membranes
Authors: Silva Brum L. F. , Elisabetsky E. , Souza D.
Published: August 2002

Linalool is a monoterpene compound reported to be a major component of essential oils of several aromatic species. Several linalool‐producing species are used in traditional medical systems for sedative purposes, including the interruption and prevention of seizures. Previous studies in mice revealed that linalool modulates glutamatergic (competitive antagonism of L‐[3H]glutamate binding, delayed intraperitoneal NMDA‐induced convulsions and blockade of intracerebroventricular Quin‐induced convulsions) and GABAergic transmission (protection against pentylenetetrazol and picrotoxin‐induced convulsions). To further clarify the anticonvulsive mechanisms of linalool, we studied the effects of linalool on binding of [3H]MK801 (NMDA antagonist) and [3H]muscimol (GABAA agonist) to mouse cortical membranes. Linalool showed a dose dependent non‐competitive inhibition of [3H]MK801 binding (IC50 = 2.97 mM) but no effect on [3H]muscimol binding. The data suggest that the anticonvulsant mode of action of linalool includes a direct interaction with the NMDA receptor complex. The data do not, however, support a direct interaction of linalool with GABAA receptors, although changes in GABA‐mediated neuronal inhibition or effects on GABA release and uptake cannot be ruled out.
Designing a belt conveyor controller in a bottling plant using fuzzy logic and genetic algorithms
Authors: Braglia Marcello
Published: August 2002

This paper presents an industrial case study relevant to a fuzzy logic controller designed via a properly developed genetic algorithm. We consider an example of a fuzzy logic‐based industrial process‐controller. In particular, we deal with the problem of controlling the speed of a belt conveyor for glass containers in a bottling plant. The primary objective of the controller is to guarantee the continuous feed to the filling station, in the presence of frequent gaps between bottles. The secondary objective is to reduce the impact speed between arriving bottles and those standing in the queue, in order to reduce the plant noise. High‐performance parameters of the fuzzy controller are found by a properly developed genetic algorithm. The results provided by Monte Carlo simulations demonstrate that, with such controllers, it is possible to achieve both the objectives mentioned above. Copyright © 2001 John Wiley & Sons, Ltd.
Standard operating procedures ‐ a novel perspective
Authors: Hattemer‐Apostel Rita
Published: August 2002

Standard operating procedures (SOPs) are a vital component in any quality management system. Written instructions on standardized processes provide guidance to ensure that activities are conducted in a consistent way, thus leading to reliable product and service quality. SOPs should be prepared in full compliance with guidelines and regulations and must mirror current organizational practices. Many items must be considered in connection with SOPs and a particular format was used in this article to discuss a selection of those items. Compliance with SOPs will depend on the way employees are familiarized with the concept and contents of SOPs. Novel approaches are offered for SOP training, based on the selected items associated with SOPs, in order to ‘infect’ employees with the ‘SOP virus’ – a prerequisite for high‐quality products and services. Copyright © 2001 John Wiley & Sons, Ltd.
The efficacy of a test and ESS program
Authors: Katz Asaf , Argov Nitay , Shapira Alon , Gershman Israel , Refaeli Nir
Published: August 2002

Statistical results of all the 1621 failure analyses, which cover a four‐year effort, are presented. The failure analyses were part of an elaborate test and ESS process of a high‐reliability system. Of the failure analyses, 97.5% identified the root cause. The classification of the failures by 11 root cause classes, including the test and ESS process itself is provided. The distribution of failure root causes detected during the various phases of the process is shown. Each test phase was analyzed according to the share of failures found and the fraction of failures that occurred during that phase. Applying a linear formula that summarizes the relative efficacy of each test phase compares the performances of the various phases. The term efficacy is used to describe the ability of a test phase to reveal failures without generating new problems. Copyright © 2002 John Wiley & Sons, Ltd.
Structural motifs as functional microdomains in G‐protein‐coupled receptors: Energetic considerations in the mechanism of activation of the serotonin 5‐HT2A receptor by disruption of the ionic lock of the arginine cage*
Authors: Visiers Irache , Ebersole Barbara J. , Dracheva Stella , Ballesteros Juan , Sealfon Stuart C. , Weinstein Harel
Published: August 2002

Studies of the structural changes associated with the activation of several G‐protein coupled receptors (GPCRs) have suggested that the cytoplasmic ends of transmembrane helices 6 and 3 move apart, but the molecular mechanisms involved in the helix rearrangements are not known. The cytoplasmic end of helix 3 contains the structural motif DRY that is universally conserved in the sequences of GPCRs in the rhodopsin family. Using computational modeling of the 5‐HT2A receptor, we find that an interaction of the central arginine in this motif, R3.50, with the conserved acidic side chain of the neighboring Asp (D3.49) is supplemented by a concomitant interaction with the conserved glutamate in helix 6, E6.30. Thus, R3.50 is caged in the inactive state of the receptor by its interaction with D3.49 and other conserved residues including E6.30. In the model, these interactions support the close packing of the ends of helices 3 and 6 that contributes to the stabilization of the inactive receptor state. To understand the energetic determinants for the stabilization of the inactive form of the receptor, and the mode in which activation can free the caged R3.50, we compared the electrostatic properties of the conserved residues in the conformations corresponding to the active and inactive forms of the receptor. These comparisons were analyzed with respect to a hypothesis about the role of protonation of D3.49 and E6.30 in the activation mechanism. The inferences from the computational analysis were used to design mutations to probe the mechanistic hypothesis. The experiments with mutant receptor constructs show that the removal of the acidic side‐chain at either position 3.49 or 6.30, or both, increases the level of ligand‐independent (constitutive) activity of the receptor. These results support the hypothesis regarding the role of these acidic residues in stabilizing the inactive state, because mutations that weaken the interactions should facilitate the receptor's transition to the active conformation. Hence we find a constitutively active state for receptor constructs in which E6.30 is mutated to N, Q, or L. The weakening of the helix 3–helix 6 link that results from these substitutions allows the helices to move apart in the activated state of the receptor. From the results of the computational analysis combined with related experimental probing of receptor function we thus propose a general molecular model for the role of the structural motif that include D3.49, R3.50, and E6.30, as a functional microdomain in the receptor activation mechanism. © 2002 Wiley Periodicals, Inc. Int J Quantum Chem 88: 65–75, 2002
Molecular orbital studies relating to potential anticancer activity of cis‐platinum ammines
Authors: Boudreaux Edward A.
Published: August 2002

The binding of platinum(II) diammines to 1‐methylcytosine and guanine has been reevaluated from earlier published molecular orbital calculations, in which the Löwdin overlap charge density has been defined and evaluated for platinum–ammine bonds in the Pt(II) diammine drugs and the PN bonds involved with 1‐methylcytosine and guanine. It is also shown that the effectiveness of anticancer activity is reduced in the Pt(II) diammine drugs, with increasing methyl substitution on the ammine nitrogen. © 2001 John Wiley & Sons, Inc. Int J Quant Chem 83: 255–258, 2001
Attachment of alkali cations on β‐D‐glucopyranose: matrix‐assisted laser desorption/ionization time‐of‐flight studies and ab initio calculations
Authors: Botek E. , Debrun J. L , Hakim B. , Morin‐Allory L.
Published: August 2002

In matrix‐assisted laser desorption/ionization mass spectrometry, carbohydrates ionize by attachment of an alkali cation, and the ion yield varies with the nature of the cation. In an attempt to contribute to the understanding of the mechanisms involved, we have conducted matrix‐assisted laser desorption/ionization time‐of‐flight (MALDI‐TOF) experiments on the simple glucose molecule with the alkali cations Li+, Na+ and K+, and have also performed ab initio calculations. The calculations show that, for the most stable carbohydrate‐cation geometry, the carbohydrate ring is twisted and the cation is coordinated to four oxygen atoms. Calculations also show that in these complexes the positions of the three cations are very similar, and the smaller the cation, the closer it is to the oxygen atoms. Finally, the calculated formation enthalpies of the different complexes agree with the experimental results obtained for the order of stability of these complexes. Copyright © 2001 John Wiley & Sons, Ltd.
Simultaneous determination of a drug candidate and its metabolite in rat plasma samples using ultrafast monolithic column high‐performance liquid chromatography/tandem mass spectrometry
Authors: Hsieh Yunsheng , Wang Gangfeng , Wang Yuguang , Chackalamannil Samuel , Brisson Jean‐Marc , Ng Kwokei , Korfmacher Walter A.
Published: August 2002

An ultrafast bioanalytical method using monolithic column high‐performance liquid chromatography/tandem mass spectrometry (HPLC/MS/MS) was evaluated for the simultaneous determination of a drug discovery compound and its metabolite in plasma. Baseline separation of the two compounds was achieved with run times of 24 or 30 s under isocratic or gradient conditions, respectively. The monolithic column HPLC/MS/MS system offers shorter chromatographic run times by increasing flow rate without sacrificing separation power for the drug candidate and its biotransformation product (metabolite). In this work, the necessity for adequate chromatographic resolution was demonstrated because the quantitative determination of the drug‐related metabolism product was otherwise hampered by interference from the dosed drug compound. The chromatographic performance of a monolithic silica rod column as a function of HPLC flow rates was investigated with a mixture of the drug component and its synthetic metabolite. The assay reliability of the monolithic column HPLC/MS/MS system was checked for matrix ionization suppression using the post‐column infusion technique. The proposed methods were successfully applied to the analysis of study rat plasma samples for the simultaneous quantitation of both the dosed drug and its metabolite. The analytical results obtained by the proposed monolithic column methods and the ‘standard’ silica particle‐packed HPLC column method were in good agreement, within 10% error. Copyright © 2002 John Wiley & Sons, Ltd.
A rapid and sensitive liquid chromatography/negative ion tandem mass spectrometry method for the determination of an indolocarbazole in human plasma using internal standard (IS) 96‐well diatomaceous earth plates for solid‐liquid extraction
Authors: Wang Amy Q. , Zeng Wei , Musson D. G. , Rogers J. D. , Fisher A. L.
Published: August 2002

An Erratum has been published for this article in Rapid Communications in Mass Spectrometry 16 (16) 2002, 1610

A sensitive liquid chromatography/tandem mass spectrometry (LC/MS/MS) method for the quantitation of a novel topoisomerase I inhibitor (indolocarbazole derivative I) in human plasma was developed to support clinical studies. Drug and internal standard were isolated from plasma by solid‐liquid extraction using 96‐well diatomaceous earth plates. Various extraction solvents were evaluated for extraction of I and 9% isopropyl alcohol (IPA) in methyl‐tert‐butyl ether (MtBE) was chosen as the optimal extraction solvent. The sensitivity of this LC/MS/MS method is 10× higher in negative ion mode using alkaline conditions than in positive ion mode using a wide range of pH's. A mobile phase with 2 mM ammonium hydroxide enhanced the sensitivity in negative ion mode over other volatile bases. The calibration curve for compound I is linear over the range 0.05–200 ng/mL in plasma and the lower limit of quantification (LLOQ) of the assay is 0.05 ng/mL, when 0.25 mL of plasma is processed. The method was fully validated and successfully applied to plasma samples from clinical studies. Performing chromatography at high pH, for enhanced negative ion sensitivity, eliminates the need for post‐column addition of base. Furthermore, the 96‐well diatomaceous earth plate extraction offers the following advantages over liquid‐liquid extraction (LLE) or solid‐phase extraction (SPE): clean sample extracts with reduced sample preparation time; increased sample throughput; no conditioning or washing steps; and a neutral eluate applicable to acid/base labile compounds. Copyright © 2002 John Wiley & Sons, Ltd.
Mucosal immune network in the gut for the control of infectious diseases
Authors: Iijima Hideki , Takahashi Ichiro , Kiyono Hiroshi
Published: August 2002

The common mucosal immune system (CMIS) consists of an integrated cross‐communication pathway of lymphoid tissues made up of inductive and effector sites for host protection against pathogenic microorganisms. Major effector molecules of the CMIS include IgA antibodies and cytokines, chemokines and their corresponding receptors. Secretory IgA (S‐IgA), the major immunoglobulin, is induced by gut‐associated lymphoreticular tissue (GALT)‐derived B cells with the help of Th1‐ and Th2‐type CD4+ T lymphocytes. Cytotoxic T lymphocytes (CTLs) in the mucosal epithelium, a subpopulation of intraepithelial lymphocytes (IELs), also help maintain the mucosal barrier. The CMIS is unique in that it can provide both positive and negative signals for the induction and regulation of immune responses in both the mucosal and systemic compartments after oral or nasal antigen exposure. Prevention of infection through mucosal surfaces can be achieved by the CMIS through connections between inductive (e.g. GALT) and effector tissues. When vaccine antigens are enterically administered together with mucosal adjuvants [e.g. cholera toxin (CT), heat‐labile toxin produced by Escherichia coli (LT) and IL‐12], antigen‐specific Th1/Th2 and IgA B cell responses are induced simultaneously in the mucosal effector compartment. Since these antigen‐specific immune responses are not generated by oral vaccine without mucosal adjuvant, safe and effective adjuvants for the induction of antigen‐specific S‐IgA and CTL responses are essential for the development of mucosal vaccines for protection against infectious diseases. Finally, recent findings suggest the presence of a CMIS‐independent IgA induction pathway, which also must be considered in the development of mucosal vaccines. Copyright © 2001 John Wiley & Sons, Ltd.
Providing IP QoS over GEO satellite systems using MPLS
Authors: Ors Tolga , Rosenberg Catherine
Published: August 2002

Multi‐protocol label switching (MPLS) is a promising technology that is quickly gathering momentum as a solution for delivering quality of service (QoS) on IP‐based terrestrial networks. It is then appropriate to wonder how this technology could affect the next generation satellite networks (from at least an interoperability standpoint) and if satellite network designers should implement MPLS on their space segment (and if yes, how?). These are the main questions that this paper is addressing.

We will show how MPLS can be used on top of any layer 2 technology on the space segment, to provide IP QoS. In particular we will discuss MPLS over ATM over satellite where MPLS is essentially used to control and manage an on‐board ATM switch fabric. Problems with MPLS and solutions will be presented. As the digital video broadcast (DVB) standard is becoming popular to be used on both the forward and return link, the different methods to carry IP over DVB will also be discussed. Copyright © 2001 John Wiley & Sons, Ltd.
Why firefighting is never enough: preserving high‐quality product development
Authors: Black Laura J. , Repenning Nelson P.
Published: August 2002

In this article, we add to insights already developed in single‐project models about insufficient resource allocation and the “firefighting” and last‐minute rework that often result by asking why dysfunctional resource allocation persists from project to project. We draw on data collected from a field site concerned about its new product development process and its quality of output to construct a simple model that portrays resource allocation in a multi‐project development environment. The main insight of the analysis is that under‐allocating resources to the early phases of a given project in a multi‐project environment can create a vicious cycle of increasing error rates, overworked engineers, and declining performance in all future projects. Policy analysis begins with policies that were under consideration by the organization described in our data set. Those policies turn out to offer relatively low leverage in combatting the problem. We then test a sequence of new policies, each designed to reveal a different feature of the system's structure and conclude with a strategy that we believe can significantly offset the dysfunctional dynamics we discuss. The article concludes with a discussion of the challenges managers may face in implementing the strategy that can prevent persistent under‐allocation of resources to projects. Copyright © 2001 John Wiley & Sons, Ltd.
Quantitative ToF‐SIMS analysis of monomers, oxidation and trace elements in EPDM gels
Authors: Galuska Alan A.
Published: August 2002

During the production, processing and use of ethylene–propylene–diene monomer terpolymers (EPDMs), small (0.1–2 mm) visible inclusions are occasionally encountered in the polymer matrix. These inclusions are commonly called gels and result in degraded polymer performance. In this work, new cross‐sectional time‐of‐flight (ToF) SIMS methods were developed for quantitative ethylene, ethylidene–norbornene (ENB), oxidation and trace element analysis of EPDM gels. The ethylene calibrations were obtained by plotting C5H9+/C2H3+ and C8H13+/C2H3+ versus wt.% ethylene. The ENB calibration was obtained by plotting (C7H8+ + C7H10+)/2(C2H3+) versus wt.% ENB. Oxidation calibrations were obtained by plotting C2H3O+/C2H3+ versus wt.% oxygen from oxidation for both high‐ and low‐ENB EPDMs. Relative sensitivity factors were also determined for semiquantitative trace metals (V, Al, Cl, Ti, Si, S, Fe, Ni, Ca and Zn) analysis in polypropylene, EPDM and polyethylene polymers. The relative sensitivity factors determined in the different polymers were very similar, indicating the absence of substantial matrix effects. The detection limits for these trace element analyses varied from 2 to 50 ppm. The analyses of well‐characterized EPDMs (treated as unknowns) were used to verified the accuracy of these calibrations. These ToF‐SIMS methods then were used to examine the composition of a variety of EPDM gels found in industry. Copyright © 2001 John Wiley & Sons, Ltd.
Application of random effect ordinal regression model for outcome evaluation of two randomized controlled trials
Authors: Marinacci Chiara , Schifano Patrizia , Borgia Piero , Perucci Carlo A.
Published: August 2002

Cluster randomization is often used in intervention trials, yet when individuals nested within clusters are considered as the units of analysis for outcome evaluation, it cannot be assumed that the observations are statistically independent. Observations that are not statistically independent also result when repeated measures are taken over time for the same individual. Ignoring clustered observations when performing data analysis can lead to the erroneous conclusion that the intervention under study had a statistically significant effect. Moreover, individual responses are often collected on ordinal scales; thus models for continuous or categorical data are usually not appropriate. We applied a random effect ordinal regression model to data sets from two randomized controlled intervention trials that measured graded scale non‐independent responses. The first trial compared two school programmes for AIDS prevention in terms of impact (i.e., changes in the frequency of condom use). The second trial used the MOS‐HIV questionnaire to measure the quality of life of new AIDS cases four times over a one‐year follow‐up period (only results of the role‐functioning scale are reported). Regarding the first data set, the effect of the intervention was not significant, and the post‐intervention frequency of condom use was mainly attributable to the pre‐intervention frequency (p<0.01), with no differences among schools. Regarding the second data set, a borderline significant increase in the role‐functioning scale scores was observed over the follow‐up period; the results differed only slightly by intervention group; a significant (p<0.01) intra‐individual correlation of 0.4 was found. Copyright © 2001 John Wiley Sons, Ltd.
The impact of the international guideline entitled Statistical Principles for Clinical Trials (ICH E9)
Authors: Lewis J. , Louv W. , Rockhold F. , Sato T.
Published: August 2002

At the time of writing, the ICH E9 Note for Guidance entitled ‘Statistical principles for clinical trials’ has been in force in Europe, Japan and the U.S.A. for almost a year. The purpose of this paper is to review the initial progress of E9 in terms of its degree of acceptance and also in terms of any early problems which have emerged. A different means of exploring these questions has been adopted in each of the three regions. From Europe there is a regulatory perspective on statistical issues which have been found to be incompletely covered within E9 and which have been important for specific regulatory decisions. From the U.S. there is a report of the results of a survey of U.S. pharmaceutical industry opinion concerning the effect of E9 on statistical practice in drug development. From Japan there is a discussion of the shortage of qualified statisticians in Japan and the difficulties that this causes when trying to implement E9. Some overall conclusions are drawn. Copyright © 2001 John Wiley & Sons, Ltd.
A framework for practical, automated black‐box testing of component‐based software†
Authors: Edwards Stephen H.
Published: August 2002

This paper outlines a general strategy for automated black‐box testing of software components that includes automatic generation of component test drivers, automatic generation of black‐box test data, and automatic or semi‐automatic generation of component wrappers that serve as test oracles. This research in progress unifies several threads of testing research, and preliminary work indicates that practical levels of testing automation are possible. Copyright © 2001 John Wiley & Sons, Ltd.
The cholinergic system modulates kindling and kindling‐induced mossy fiber sprouting
Authors: Adams Beth , Vaccarella Liezanne , Fahnestock Margaret , Racine Ronald J.
Published: August 2002

In a previous study, our laboratory demonstrated that the intraventricular infusion of nerve growth factor (NGF) accelerated kindling rates and enhanced mossy fiber sprouting in the absence of noticeable kindling‐associated neuronal loss. The purpose of the present study was to investigate whether these NGF effects were mediated via the cholinergic system. This study evaluated the effects of the cholinergic agonist pilocarpine and the cholinergic antagonist scopolamine on kindling rates and kindling‐induced mossy fiber sprouting in adult rats. The results showed that pilocarpine accelerated kindling rates and enhanced kindling‐induced mossy fiber sprouting in the CA3 region of the hippocampus, whereas scopolamine retarded kindling rates and blocked kindling‐induced mossy fiber sprouting in the CA3 and IML regions. These findings suggest that the cholinergic system may contribute to the long‐term structural and functional alterations that are characteristic of the kindled state. Moreover, these data provide support for the hypothesis that NGF infusions may mediate kindling and kindling‐induced mossy fiber sprouting via regulation of the cholinergic system. Synapse 44:132–138, 2002. © 2002 Wiley‐Liss, Inc.
Seismic rehabilitation of a base‐isolated building using viscous dampers
Authors: Hart G. C. , Brandow G. , Johnston R.
Published: August 2002

The seismic rehabilitation of steel buildings can be effectively done using viscous dampers. The dampers increase the energy loss without increasing the stiffness of the building and associated acceleration‐related earthquake damage. This paper discusses how a base‐isolated building used viscous dampers for seismic rehabilitation. Copyright © 2001 John Wiley & Sons, Ltd.
Mechanistic Study of Partial Oxidation of Methane to Syngas Using In Situ Time‐Resolved FTIR and Microprobe Raman Spectroscopies
Authors: Zheng Weng Wei , Shu Chen Ming , Lin Wan Hui
Published: August 2002

In situ time‐resolved Fourier transform infrared (FTIR) and microprobe Raman spectroscopies were used to characterize the reaction mechanisms of the partial oxidation of methane to syngas over SiO2‐ and γ‐Al2O3‐supported rhodium and ruthenium catalysts. The interaction of both pure methane and a methane/oxygen mixture at a stoichiometric feed ratio with an oxygen‐rich catalyst surface led to the formation of CO2 and H2O as the primary products. For the H2‐pretreated samples, the reaction mechanisms with the catalysts differ. Only Rh/SiO2 is capable of catalyzing the direct oxidation of methane to syngas, while syngas formation over Rh/g‐Al2O3, Ru/SiO2, and Ru/g‐Al2O3 can be achieved mainly via a combustion‐reforming scheme. The significant difference in the mechanisms for partial oxidation of methane to syngas over the catalysts can be correlated to the differences in the concentration of oxygen species (O2−) on the catalyst surface during the reaction, mainly due to the difference in the nature of the metals and supports. © 2002 The Japan Chemical Journal Forum and Wiley Periodicals, Inc. Chem Rec 2:102–112, 2002: Published online in Wiley InterScience (www.interscience.wiley.com) DOI 10.1002/tcr.10016
Reversing the “standard” direction: Science emerging from the lives of African American students
Authors: Seiler Gale
Published: August 2002

Recognizing the persistent science achievement gap between inner‐city African American students and students from mainstream, White society, this article suggests that the imposition of external standards on inner‐city schools will do little to ameliorate this gap because such an approach fails to address the significance of the social and cultural lives of the students. Instead, it is suggested that the use of critical ethnographic research would enable educators to learn from the students how science education can change to meet their aims and interests. The article includes a report on how a science lunch group in an inner‐city high school forged a community based on respect and caring and how this community afforded African American male teens the opportunity to participate in science in new ways. © 2001 John Wiley & Sons, Inc. J Res Sci Teach 38: 1000–1014, 2001