bluuebunny/crossref_metadata_2025 huggingface dataset:
Hydrolysis of N‐aryl thioncarbamate esters. Modified Marcus equation for reactions with asymmetric intrinsic barriers
Authors: Humeres Eduardo , Zucco Cesar , Nunes Mauricea , Debacher Nito A. , Nunes Ricardo J.
Published: October 2002

The hydrolysis of ethyl N‐p‐substituted arylthioncarbamates was studied at 100 °C in the pH range 6.5–12.5. No general catalysis was found, and the presence of an isothiocyanate intermediate was detected, indicating that the alkaline hydrolysis occurs by an E1cb mechanism. From the pH–rate profiles, the first‐order rate constants kE for the elimination step of the thioncarbamate anion forming the isothiocyanate intermediate were determined. The alkaline hydrolysis of p‐substituted arylisothiocyanates was studied at 25 °C in 0.1–0.3 M solutions of NaOH and in 0.1–0.3 M aqueous ethanol solutions, at different concentrations of NaOH. The second‐order rate constants for the addition reaction with hydroxide (kOH) and ethoxide (kA) ions were obtained. Leffler plots for the elimination of the ethoxide ion from the arylthioncarbamate anion and for the addition of the ethoxide ion to the arylisothiocyanate were linear. From Leffler's equation, with the sole condition that dαL/dΔG should be constant, a modified Marcus equation (MME) was obtained, where a parameter p (or q for the reverse reaction) defined the asymmetry of the intrinsic barrier. (When p = 1/2 the barrier is symmetric and the MME becomes the Marcus equation in the usual form.) For the addition–elimination reaction studied, both Leffler plots were adjusted to MME with the asymmetric parameter p = 0.694 ± 0.002 for the addition and q = 0.307 ± 0.002 for the elimination reaction. The intrinsic barrier was $\Delta G_{0}^{\neq} = 24.75 \pm 0.02\,\hbox{kcal mol}^{-1}$ and |ΔGmax| = 438 ± 4 kcal mol−1 (1 kcal = 4.184 kJ). The addition reaction was exoergic and, as expected from the high intrinsic barrier, αL changed very little in the series (0.679–0.683); the transition state was product‐like, and it moved towards the reagents with increasing exoergicity. Copyright © 2002 John Wiley & Sons, Ltd.
Crosslinking of vinyl‐terminated biphenyl and naphthalene side‐chain liquid‐crystalline poly(epichlorohydrin) derivatives
Authors: Callau Lourdes , Mantecón Ana , Reina José Antonio
Published: October 2002

We performed the crosslinking of vinyl‐terminated biphenyl and naphthalene side‐chain liquid‐crystalline polyethers using peroxide‐type initiators with and without the addition of tertiary amine promoters. The crosslinking temperatures were chosen in the range of mesophase stability to allow the mesophase order to be frozen. The biphenyl derivatives, with a high isotropization temperature, were crosslinked to a large extent. This led to anisotropic thermosets. To crosslink naphthalene derivatives, amine promoters were needed, but degrees of crosslinking were lower, and anisotropic elastomers were obtained. Crosslinking processes were studied by differential scanning calorimetry, polarized optical microscopy, and Fourier transform infrared spectroscopy. The nature of the frozen mesophase was confirmed by X‐ray diffraction studies on mechanically oriented samples. © 2002 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 40: 2237–2244, 2002
Benzyl alcohols as accelerators in the photoinitiated cationic polymerization of epoxide monomers
Authors: Crivello James V. , Acosta Ortiz Ricardo
Published: October 2002

Benzyl alcohols display marked accelerating effects on the onium salt photoinitiated cationic ring‐opening polymerizations of epoxide monomers. The participation of radicals in these polymerizations was demonstrated, and a pronounced accelerating effect on the polymerization rate was observed depending on the character of the substituent on the benzene ring of the alcohol. 4‐Methoxybenzyl alcohol was considerably more reactive than benzyl alcohol, whereas the analogous chloro‐ and nitrosubstituted compounds were less reactive. Piperonyl alcohol was even more reactive as an accelerator in these polymerizations. The UV irradiation of an onium salt cationic photoinitiator generates Brönsted acids that initiate the cationic ring‐opening polymerization of the epoxide monomer. In the presence of benzyl alcohol, the usual polymerization mechanism is diverted and proceeds by a more‐rapid activated monomer mechanism. As a result, benzyl ether groups are incorporated at the termini of the polymer chains. Aryl radicals that are also generated by photolysis of the onium salt abstract labile benzyl ether protons, and the benzyl ether radicals that are produced are subsequently oxidized by the onium salt to afford the corresponding benzyl carbocations. This takes place by a chain process. The polymer bound benzyl cations serve as additional sites for the initiation of cationic polymerization. It is proposed that these two mechanisms acting in synergy with one another account for the observed accelerating effect on the polymerization rate. © 2002 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 40: 2298–2309, 2002
Chain‐transfer reaction in the radical polymerization of di‐n‐butyl itaconate at high temperatures
Authors: Hirano Tomohiro , Takeyoshi Ryoko , Seno Makiko , Sato Tsuneyuki
Published: October 2002

Radical polymerizations of di‐n‐butyl itaconate were investigated. Unexpected resonances (C resonances) were observed in 13C NMR spectra of CO of poly(di‐n‐butyl itaconate)s [poly(DBI)s] obtained at temperatures higher than 60 °C, although two kinds of carbonyl groups showed splittings due to triad tacticities in the spectra of polymers obtained at lower temperatures. The poly(DBI)s formed by the different kinds of initiators or formed in the presence of chain‐transfer agents showed hardly any changes in the intensities of the C resonances; this indicated that the C resonances were not due to the structures formed through initiating and terminating reactions. The poly(DBI)s obtained at different yields showed only a slight increase in the intensities of the C resonances with the yield, which suggested that the C resonances were not attributable to the intermolecular chain‐transfer reaction to the monomer and/or polymer. However, the intensities of the C resonances significantly increased with a decreasing feed monomer concentration; this suggested that intramolecular chain‐transfer reactions took place at high temperatures. Furthermore, a Cu complex‐catalyzed atom transfer radical polymerization mechanism was revealed to be effective for suppressing the intramolecular chain‐transfer reaction at 60 °C. © 2002 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 40: 2415–2426, 2002
Controlled synthesis and chemical modification of unsaturated aliphatic (Co)polyesters based on 6,7‐dihydro‐2(3H)‐oxepinone
Authors: Lou Xudong , Detrembleur Christophe , Lecomte Philippe , Jérôme Robert
Published: October 2002

A pure unsaturated cyclic ester, 6,7‐dihydro‐2(3H)‐oxepinone (DHO2), was prepared by a new synthetic route. The copolymerization of DHO2 with ϵ‐caprolactone (ϵCL) was initiated by aluminum isopropoxide [Al(OiPr)3] at 0 °C as an easy way to produce unsaturated aliphatic polyesters with nonconjugated CC double bonds in a controlled manner. The chain growth was living, as certified by the agreement between the experimental molecular weight at total monomer conversion and the value predicted from the initial monomer/initiator molar ratio. The polydispersity was reasonably low (weight‐average molecular weight/number‐average molecular weight ≤ 1.2). The homopolymerization of DHO2 was, however, not controlled because of fast intramolecular transesterification. Copolymers of DHO2 and ϵCL were quantitatively oxidized with the formation of epoxides containing chains. The extent of the epoxidation allowed the thermal properties and thermal stability of the copolyesters to be modulated. The epoxidized copolyesters were successfully converted into thioaminated chains, which were then quaternized into polycations. No degradation occurred during the chemical modification. © 2002 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 40: 2286–2297, 2002
Synthesis and properties of polyacetylenes with salicylideneaniline groups
Authors: Karim S. M. Abdul , Nomura Ryoji , Masuda Toshio
Published: October 2002

Acetylenes containing salicylideneaniline groups—N‐salicylidene‐3‐ethynylaniline (1), N‐(3‐t‐butylsalicylidene)‐3‐ethynylaniline (2), and N‐(3‐t‐butylsalicylidene)‐4‐ethynylaniline (3)—polymerized smoothly and gave yellow to red polymers in excellent yields when a rhodium catalyst was employed. Polymers with alkyl substituents on the aromatic rings [poly(2) and poly(3)] were soluble in CHCl3, tetrahydrofuran, and so forth, whereas the polymer without alkyl substituents [poly(1)] was insoluble in any solvent. N‐(3‐t‐Butylsalicylidene)propargylamine did not provide any polymer. Thermogravimetric analyses of the resultant polymers exhibited good thermal stability (To, onset temperature of weight loss > 300 °C). The ultraviolet–visible spectra of the polymers showed absorption maxima and cutoff wavelengths around 360 and 520 nm, respectively. The polymers exhibited largely Stokes‐shifted fluorescence (emission wavelength ≃ 550 nm) upon photoexcitation at 350 nm, which resulted from the photoinduced intramolecular proton transfer. © 2002 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 40: 2458–2463, 2002
Poly(4‐vinylpyridine) as the host ligand of metal‐containing chromophores for second‐order nonlinear optical active materials
Authors: Caruso Ugo , De Maria Antonella , Panunzi Barbara , Roviello Antonio
Published: October 2002

Two formulas of grafted polymers with metal‐containing chromophores, potentially suitable for second‐order nonlinear optics applications, are described. Two chromophores were obtained from a tridentate ligand coordinated to Cu(II) or Pd(II) ions. The organometallic chromophore fragments were grafted to poly(4‐vinylpyridine) by the pyridinic nitrogen of the host polymer. Some qualities displayed by the new metallated polymers are remarkable: (1) a high value of the first hyperpolarizability coefficient of the chromophores, (2) a high content of the grafted chromophore in the polymers (up to 60 wt %), (3) a considerable increase in the glass‐transition temperatures (up to 240 °C), (4) good thermal stability in air (ca. 280 °C), and (5) good optical transparency of the films. © 2002 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 40: 2987–2993, 2002
Synthesis of biodegradable copolymers with low‐toxicity zirconium compounds. III. Synthesis and chain‐microstructure analysis of terpolymer obtained from L‐lactide, glycolide, and ϵ‐caprolactone initiated by zirconium(IV) acetylacetonate
Authors: Dobrzynski Piotr
Published: October 2002

Zirconium(IV) acetylacetonate [Zr(acac)4] is a very good initiator for the terpolymerization of glycolide with L‐lactide and ϵ‐caprolactone. The microstructure of the obtained terpolymer was determined by NMR spectroscopy and then compared with terpolymers obtained in the presence of stanous(II) octoate [Sn(oct)2]. Samples obtained with Zr(acac)4 were characterized by a segmental‐chain microstructure. Apart from relatively long lactidyl microblocks, there were also segments made of random copolymer of glycolide with lactide. Such a structure is formed as a result of strong transesterification caused by active caproyl chain endings attacking the glycolidyl groups. Domination of this type of transestrification is shown. The growth of terpolymer chains and the influence of transesterification on gradual changes of the microstructure of the forming terpolymer chain were examined. Significant differences among glycolide, lactide, and the least reactive caprolactone were observed. The results of differential scanning calorimetric examinations of the obtained terpolymers are presented. Differences between the structures of random terpolymers obtained during terpolymerization initiated by Sn(oct)2 and those obtained by Zr(acac)4 influence their thermal properties. © 2002 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 40: 3129–3143, 2002
Polyetherether ketone/polyarylethersulfone blends: Thermal and compatibility aspects
Authors: Nandan Bhanu , Kandpal L. D. , Mathur G. N.
Published: October 2002

The compatibility behavior of polyetherether ketone (PEEK) with poly(ether sulfone) (PES) has been reexamined using differential scanning calorimetry (DSC), scanning electron microscopy (SEM), and extrudate swell measurements. The blends were prepared by both melt‐blending and solution‐blending techniques. The phase behavior of blends is strongly affected by the blending technique used. Blends prepared by solution‐blending are compatible in the entire composition range on the basis of the single composition‐dependent glass transitions and exhibit lower critical solution temperature (LCST) behavior. LCST was near 340 °C around which the crystalline melting point of PEEK exists. Near LCST melting‐induced movement of molecular chains disturbs the initial homogeneous state of the solution blends and leads to a phase‐separated state that is thermodynamically more stable in the absence of strong specific interactions between the homopolymers. Contrary to the solution‐blended samples, melt‐blended samples were in the phase‐separated state even at a lower processing temperature of 300 °C. Two glass transitions corresponding to a PEEK‐rich and a PES‐rich phase were found for all compositions. From the measured glass transition of phase‐separated blends, weight fractions of PES and PEEK dissolved in each phase were determined using the Fox equation. Compatibility is greater in the PEEK‐rich compositions than in the PES‐rich compositions. PEEK dissolves more in PES‐rich phases than does PES in the PEEK‐rich phase. Variation of the specific heat increment (ΔCp) at the glass transition with composition also supports these inferences. Solution‐blended samples, quenched from 380 °C, also indicated similar behavior but were slightly more compatible. The aforementioned results are consistent with those inferred from SEM studies and extrudate swell measurements that show a greater compatibility in PEEK‐rich compositions than in PES‐rich compositions. © 2002 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 40: 1407–1424, 2002
Simulation of orientation of uniaxially stretched poly(vinyl phenol) by molecular dynamics
Authors: Gestoso Patricia , Brisson Josée
Published: October 2002

Molecular dynamics were performed for the simulation of the uniaxial deformation of poly(vinyl phenol) under periodic boundary conditions with the Parrinello–Rahman scheme followed by relaxation under NVT conditions (constant number of atoms, volume, and temperature). Changes in the orientation of the main chain, benzene segments, and hydrogen bonds were analyzed with the second‐order Legendre polynomial, 〈P2(cos θ)〉. Conformational changes were also followed. During deformation, backbone and phenyl rings both initially orient parallel to the draw direction. After relaxation, the chain is oriented parallel to the deformation direction, and side groups orient approximately perpendicular to this direction, in agreement with experimental data reported in the literature. Orientation values are higher than experimental values, as expected from the limited relaxation time range attainable in the simulations. Deformation proceeds by changes from gauche conformers to nontrans, nongauche, and trans conformers, whereas relaxation mainly allows high‐energy nontrans, nongauche conformers to convert into lower energy trans conformers. Values of the α angle for ring and bonded OH segments agree with those in the literature. Differences observed for free hydroxyl moieties are discussed. © 2002 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 40: 1601–1625, 2002
Melt blending of ethylene‐vinyl alcohol copolymer/clay nanocomposites: Effect of the clay type and processing conditions
Authors: Artzi N. , Nir Y. , Narkis M. , Siegmann A.
Published: October 2002

Ethylene‐vinyl alcohol copolymer (EVOH)/clay nanocomposites were prepared via dynamic melt blending. The effect of the processing parameters on blends containing two clay types in different amounts was examined. The blends were characterized with a Brabender plastograph and capillary rheometer, differential scanning calorimetry, dynamic mechanical thermal analysis (DMTA), X‐ray diffraction (XRD), transmission electron microscopy (TEM), and thermogravimetric analysis (TGA). XRD showed advanced EVOH intercalation within the galleries, whereas TEM images indicated exfoliation, thereby complementing the XRD data. A dilution process with EVOH and clay treatment in an ultrasonic bath before melt blending did not add to the intercalation level. Different trends were observed for the EVOHs containing two different clay treatments, one claimed to be treated for EVOH and the other for amine‐cured epoxy. They reflected the differences in the amounts of the strongly interacting polymer for the two nanocomposites. Thermal analysis showed that the melting temperature, crystallization temperature, and heat of fusion of the EVOH matrix sharply decreased with both increasing clay content and processing times. Significantly higher viscosity levels were obtained for the blends in comparison with those of the neat polymer. The DMTA spectra showed higher glass‐transition temperatures for the nanocomposites in comparison with those of the neat EVOH. However, at high clay loadings, the glass‐transition temperature remained constant, presumably because of an adverse plasticizing effect of the low moleculared mass onium ions treating the clays. The storage modulus improved when clay treated for EVOH was used, and it deteriorated when amine‐cured epoxy clay was incorporated, except for the sonicated clay. TGA results showed significant improvements in the blends' thermal stability in comparison with that of the neat EVOH, which, according to TEM, was greater for the intercalated structures rather than for exfoliated ones. © 2002 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 40: 1741–1753, 2002
Seasonal variation in respiratory syncytial virus chest infection in the tropics
Authors: Chan P.W.K. , Chew F.T. , Tan T.N. , Chua K.B. , Hooi P.S.
Published: October 2002

Respiratory syncytial virus (RSV) is the most important cause of lower respiratory tract infection (LRTI) in young children. We determined if there was a seasonal variation in Malaysia in the incidence of RSV infection in young children admitted with LRTI, and possible associations of RSV infection with local meteorological parameters. A total of 5,691 children, aged less than 24 months and hospitalized with LRTI (i.e., bronchiolitis and pneumonia) between 1982–1997, were included in this study. Nasopharyngeal samples were collected and examined for RSV by immunofluorescence, viral culture, or both. Seasonal variations were determined by analyzing the monthly RSV‐positive isolation rate via time series analysis. Possible correlations with local meteorological parameters were also evaluated.

RSV was isolated in 1,047 (18.4%) children. Seasonal variations in RSV infection rate were evident and peaked during the months of November, December, and January (test statistics [T] = 53.7, P < 0.001). This seasonal variation was evident for both bronchiolitis and pneumonia categories (T = 42.8 and 56.9, respectively, P < 0.001). The rate of RSV infection appeared to correlate with the monthly number of rain days (r = 0.26, P < 0.01), and inversely with the monthly mean temperature (r = −0.38, P < 0.001).

In the tropics, seasonal variations in the incidence of RSV infection are evident, with an annual peak in November, December, and January. This information provides a guide for healthcare provisions and implementation of RSV prevention. Pediatr Pulmonol. 2002; 34:47–51. © 2002 Wiley‐Liss, Inc.
Rhabdomyomatous dysplasia of the newborn lung associated with multiple congenital malformations of the heart and great vessels
Authors: Lienicke Uta , Hammer Hannes , Schneider Martin , Heling Kai , Wauer Roland R. , Mau Harald , Vogel Martin
Published: October 2002

Interstitial proliferation of striated muscle in the lung is extremely rare. Most cases are associated with other congenital malformations, such as lung sequestration, diaphragmatic hernia, or cardiac malformations. We describe a newborn with rhabdomyomatous dysplasia of the lung associated with multiple congenital malformations of the heart and great vessels.

The female neonate was born at 37 weeks of gestation as the second child to a 31‐year‐old woman without relevant previous medical or family history. In week 26 of gestation, a complex heart malformation and polyhydramnion were diagnosed by ultrasound. Postnatally, right lung hypoplasia, a bilobar right and left lung, anomalous drainage of the pulmonary veins, atrial and ventricular septal defects, and double‐outlet right‐ventricle and multiple aortopulmonary collaterals were described. Histological examination of a biopsy of the right lung demonstrated the presence of numerous bundles of striated muscle fibers arranged randomly in the pulmonary interstitium.

Unilateral resection of the right lung was not a therapeutic option, because the left lung had developed bronchopulmonary dysplasia with severe reduction in gas exchange as a consequence of long‐term mechanical ventilation. Symptomatic relief and palliative cardiac surgery were offered. At age 5 months, the infant died of a pulmonary hemorrhage following cardiac surgery. Pediatr Pulmonol. 2002; 34:222–225. © 2002 Wiley‐Liss, Inc.
Progressive prostate hyperplasia in adult prolactin transgenic mice is not dependent on elevated serum androgen levels
Authors: Kindblom Jon , Dillner Karin , Ling Charlotte , Törnell Jan , Wennbo Håkan
Published: October 2002

BACKGROUND

Transgenic mice overexpressing the rat prolactin (PRL) gene under control of the metallothionein‐1 promoter (Mt‐1) develop a dramatic prostatic enlargement. These animals also display significantly elevated testosterone serum levels. In this study, we aim to clarify the role of circulating androgen levels in the promotion of abnormal prostate growth in the adult PRL transgenic mouse prostate.

METHODS

Prostate morphology and androgen‐receptor distribution patterns were analyzed in castrated and testosterone substituted adult PRL transgenic and in wild‐type males.

RESULTS

Progressive prostatic hyperplasia in adult PRL transgenic males was not affected by substitution to serum testosterone levels corresponding to wild‐type. Furthermore, prolonged testosterone treatment in adult wild‐type males did not produce any significant changes in prostate growth or morphology compared with wild‐type controls. Immunohistochemical studies revealed a significantly increased proportion of androgen receptor positive epithelial cells in all lobes of the PRL transgenic prostate versus wild‐type.

CONCLUSION

The present study demonstrates that progressive prostate hyperplasia in adult PRL transgenic mice is not dependent on elevated serum androgen levels. Furthermore, prolonged androgen treatment in adult wild‐type male mice appears to have no significant effect on prostate growth. In addition, our results suggest that prolonged hyperprolactinemia results in changes in prostate epithelial and stromal cell androgen receptor distribution. Prostate 53: 24–33, 2002. © 2002 Wiley‐Liss, Inc.
Androgens block interleukin‐1β–induced promatrilysin expression in prostate carcinoma cells
Authors: Stratton M. Suzanne , Greenstein Benjamin , Udayakumar Thirupandiyur S. , Nagle Raymond B. , Bowden G. Timothy
Published: October 2002

BACKGROUND

We have shown previously that interleukin (IL) ‐1β– and IL‐6–induced promatrilysin expression is mediated by an indirect pathway that requires NFκB‐dependent synthesis of IL‐6 and STAT3 signaling. We now demonstrate that IL‐1β–induced but not IL‐6–induced promatrilysin expression can be blocked by androgens in the prostate carcinoma cell line LNCaP (lymph node–derived carcinoma cells of the prostate).

METHODS

By using enzyme‐linked immunosorbent assay analyses, promatrilysin was measured in LNCaP cells stimulated with IL‐1β or IL‐6 LNCaP‐treated cells pretreated with testosterone. In addition, promatrilysin message was measured by using Northern analyses after IL‐6–treated cells pretreated with testosterone.

RESULTS

In LNCaP treated with testosterone before IL‐1β stimulation induced promatrilysin expression was completely abrogated. Furthermore, testosterone completely abrogated NFκB transactivation activity and induction of IL‐6 protein expression and mRNA. Testosterone and 5α‐dihydrotestosterone did not have an inhibitory effect on IL‐6–induced promatrilysin expression. Testosterone also had no effect on basal promatrilysin expression or basal NFκB transactivation activity.

CONCLUSION

From these data, we conclude that testosterone blocks IL‐1β–induced promatrilysin expression by inhibition of NFκB transactivation activity, which in turn, blocks IL‐6 expression. These data suggest a mechanism in vivo by which invasive and metastatic prostatic carcinoma cell clones refractory to hormone ablation therapy may develop after chemical or surgical castration. Furthermore, these data suggest that, perhaps, upstream targets such as the cytokines IL‐1β and IL‐6 may provide alternative drug targets for inhibiting prostate cancer progression. Prostate 53: 1–8, 2002. © 2002 Wiley‐Liss, Inc.
Both retinoids and androgens are required to maintain or promote functional differentiation in reaggregation cultures of human prostate epithelial cells
Authors: Goossens Karine , Deboel Ludo , Swinnen Johannes V. , Roskams Tania , Manin Michèle , Rombauts Wilfried , Verhoeven Guido
Published: October 2002

BACKGROUND

Primary cultures and subcultures of prostate epithelial cells (PEC) proliferate markedly, but rapidly loose secretory differentiated function and androgen responsiveness. Here, we investigated whether differentiation could be restored or preserved by using three‐dimensional reaggregation cultures treated with retinoids and/or androgens.

METHODS

PEC were cultured as monolayers or as reaggregation cultures on a rotatory shaker. Reaggregation cultures were also developed from freshly isolated cells. Morphology was evaluated microscopically. Expression of cytokeratins (CKbasal for basal cells and CK18 for luminal cells), E‐cadherin, α‐ and β‐catenin, androgen receptor (AR), and prostate specific antigen (PSA) was evaluated by immunohistochemistry and/or Western blotting. Differentiated function was further evaluated by measurements of PSA in the medium and by reverse transcriptase‐polymerase chain reactions for AR, PSA, prostate specific membrane antigen, β‐microseminoprotein, and zinc‐α2‐glycoprotein. Proliferation was evaluated by immunohistochemical staining for Ki‐67.

RESULTS

Monolayer cultures of PEC expressed CKbasal as well as CK18, a combination compatible with an intermediary amplifying population of epithelial cells. No expression of PSA could be detected, and all attempts to re‐induce differentiation of PEC in classic two‐dimensional culture systems failed. In reaggregation cultures of subcultured PEC, retinoids proved essential to maintain a compact three‐dimensional structure. This effect was accompanied by increased levels of E‐cadherin and of the catenins and by a shift in the cytokeratin expression pattern toward that typical for secretory differentiated cells (CK18 only). Even in the presence of androgens, however, PSA remained undetectable. Similar effects of retinoids were observed in reaggregation cultures of freshly prepared PEC, and in the latter cultures, the combination of androgens and retinoids maintained a low level of PSA secretion for at least 40 days.

CONCLUSIONS

A combination of retinoids and androgens is able to preserve, for a prolonged period of time, some degree of secretory differentiation in freshly isolated PEC maintained in reaggregation culture. The same combination is unable to restore secretory differentiation in subcultured PEC. Prostate 53: 34–49, 2002. © 2002 Wiley‐Liss, Inc.
Fas‐Fas ligand signaling pathway mediates an interleukin‐12–induced rejection of a murine prostate tumor system
Authors: Zhang Shaobo , Zeng Guangyuan , Kao Chinghai , Gardner Thomas , Sweeney Christopher , Yang Ning‐Sun , Eble John N. , Cheng Liang
Published: October 2002

BACKGROUND

Recent data suggest that anti‐tumor activities of interleukin‐12 (IL‐12) involve the induction of apoptosis. Fas (APO‐1/CD95) is a type I membrane protein that is capable of initiating an apoptosis signaling pathway when bound to its ligand (FasL). We undertook this study to test the hypothesis that Fas‐FasL–mediated apoptosis plays a role in IL‐12–induced tumor regression.

METHODS

An mIL‐12 expression vector driven by cytomegalovirus promoter was used to express murine IL‐12 cDNA in the RM‐9 murine prostate carcinoma cell line. Control RM‐9 cells and RM‐9 cells stably transfected with IL‐12 gene (RM‐9‐IL12) were inoculated subcutaneously in 4‐ to 6‐week‐old male C57BL/J6 mice. Tumor size was measured every 3 days. Western blot and immunohistochemical assays were used to evaluate Fas and FasL protein expression. In situ fluorescent end labeling was used to label apoptotic cells.

RESULTS

IL‐12–expressing RM‐9 prostate carcinoma cells transplanted into C57BL/J6 mice grew more slowly than control RM‐9 cells and vector control RM‐9‐Luc cells. The average survival time of the RM‐9‐IL12 mice was longer than 53 days, whereas the mean survival for mice transplanted with control RM‐9 cells was only 16 days. Apoptotic cells were more numerous in RM‐9‐IL12 tumors: 10.3% vs. 1.5% in control (P = 0.001). Fas and FasL proteins were increased approximately twofold in the RM‐9‐IL12 tumors compared with the RM‐9 control tumors as determined by Western blot and immunohistochemical analyses (P < 0.05).

CONCLUSION

The Fas‐FasL–mediated apoptosis pathway may contribute to the IL‐12–induced rejection of prostate carcinoma. Prostate 53: 69–76, 2002. © 2002 Wiley‐Liss, Inc.
Towards atomic resolution with crystals grown in gel: The case of thaumatin seen at room temperature
Authors: Sauter Claude , Lorber Bernard , Giegé Richard
Published: October 2002

One reason for introducing a gel in the crystallization medium of proteins is its ability to reduce convection in solution. This can lead to better nucleation and growth conditions, and to crystals having enhanced diffraction properties. We report here the X‐ray characterization at room temperature of high‐quality crystals of the intensely sweet thaumatin prepared in a sodium tartrate solution gelified with 0.15% (m/v) agarose. Using a synchrotron radiation, these crystals diffracted to a previously unachieved resolution. A diffraction dataset was collected from four crystals at a resolution of 1.2 Å with a Rsym of 3.6% and a completeness of 99%. Refinement was carried out to a final crystallographic R‐factor of 12.0%. The quality of the electron density map allowed for the observation of fine structural details in the protein and its solvation shell. Crystallization in gel might be used more generally to improve the quality of macromolecular crystals. Advantages provided by the gelified medium in the frame of structural studies are emphasized. Proteins 2002;48:146–150. © 2002 Wiley‐Liss, Inc.
Model of the αLβ2 integrin I‐domain/ICAM‐1 DI interface suggests that subtle changes in loop orientation determine ligand specificity
Authors: Legge Glen B. , Morris Garrett M. , Sanner Michel F. , Takada Yoshikazu , Olson Arthur J. , Grynszpan Flavio
Published: October 2002

The interaction of the αLβ2 integrin with its cellular ligand the intercellular adhesion molecule‐1 (ICAM‐1) is critical for the tight binding interaction between most leukocytes and the vascular endothelium before transendothelial migration to the sites of inflammation. In this article we have modeled the αL subunit I‐domain in its active form, which was computationally docked with the D1 domain of the ICAM‐1 to probe potential protein‐protein interactions. The experimentally observed key interaction between the carboxylate of Glu 34 in the ICAM‐1 D1 domain and the metal ion‐dependent adhesion site (MIDAS) in the open αL I‐domain was consistently reproduced by our calculations. The calculations reveal the nature of the αLβ2/ICAM‐1 interaction and suggest an explanation for the increased ligand‐binding affinity in the “open” versus the “closed” conformation of the αL I‐domain. A mechanism for substrate selectivity among αL, αM, and α2 I‐domains is suggested whereby the orientation of the loops within the I‐domain is critical in mediating the interaction of the Glu 34 carboxylate of ICAM‐1 D1 with the MIDAS. Proteins 2002;48:151–160. © 2002 Wiley‐Liss, Inc.
Normal mode analysis of macromolecular motions in a database framework: Developing mode concentration as a useful classifying statistic
Authors: Krebs W. G. , Alexandrov Vadim , Wilson Cyrus A. , Echols Nathaniel , Yu Haiyuan , Gerstein Mark
Published: October 2002

We investigated protein motions using normal modes within a database framework, determining on a large sample the degree to which normal modes anticipate the direction of the observed motion and were useful for motions classification. As a starting point for our analysis, we identified a large number of examples of protein flexibility from a comprehensive set of structural alignments of the proteins in the PDB. Each example consisted of a pair of proteins that were considerably different in structure given their sequence similarity. On each pair, we performed geometric comparisons and adiabatic‐mapping interpolations in a high‐throughput pipeline, arriving at a final list of 3,814 putative motions and standardized statistics for each. We then computed the normal modes of each motion in this list, determining the linear combination of modes that best approximated the direction of the observed motion. We integrated our new motions and normal mode calculations in the Macromolecular Motions Database, through a new ranking interface at http://molmovdb.org. Based on the normal mode calculations and the interpolations, we identified a new statistic, mode concentration, related to the mathematical concept of information content, which describes the degree to which the direction of the observed motion can be summarized by a few modes. Using this statistic, we were able to determine the fraction of the 3,814 motions where one could anticipate the direction of the actual motion from only a few modes. We also investigated mode concentration in comparison to related statistics on combinations of normal modes and correlated it with quantities characterizing protein flexibility (e.g., maximum backbone displacement or number of mobile atoms). Finally, we evaluated the ability of mode concentration to automatically classify motions into a variety of simple categories (e.g., whether or not they are “fragment‐like”), in comparison to motion statistics. This involved the application of decision trees and feature selection (particular machine‐learning techniques) to training and testing sets derived from merging the “list” of motions with manually classified ones. Proteins 2002;48:682–695. © 2002 Wiley‐Liss, Inc.
Protein molecular dynamics with electrostatic force entirely determined by a single Poisson‐Boltzmann calculation
Authors: Lu Ben Zhuo , Chen Wei Zu , Wang Cun Xin , Xu Xiao‐jie
Published: October 2002

The electrostatic force including the intramolecular Coulombic interactions and the electrostatic contribution of solvation effect were entirely calculated by using the finite difference Poisson‐Boltzmann method (FDPB), which was incorporated into the GROMOS96 force field to complete a new finite difference stochastic dynamics procedure (FDSD). Simulations were performed on an insulin dimer. Different relative dielectric constants were successively assigned to the protein interior; a value of 17 was selected as optimal for our system. The simulation data were analyzed and compared with those obtained from 500‐ps molecular dynamics (MD) simulation with explicit water and a 500‐ps conventional stochastic dynamics (SD) simulation without the mean solvent force. The results indicate that the FDSD method with GROMOS96 force field is suitable to study the dynamics and structure of proteins in solution if used with the optimal protein dielectric constant. Proteins 2002;48:497–504. © 2002 Wiley‐Liss, Inc.
Prediction of protein solvent accessibility using support vector machines
Authors: Yuan Zheng , Burrage Kevin , Mattick John S.
Published: October 2002

A Support Vector Machine learning system has been trained to predict protein solvent accessibility from the primary structure. Different kernel functions and sliding window sizes have been explored to find how they affect the prediction performance. Using a cut‐off threshold of 15% that splits the dataset evenly (an equal number of exposed and buried residues), this method was able to achieve a prediction accuracy of 70.1% for single sequence input and 73.9% for multiple alignment sequence input, respectively. The prediction of three and more states of solvent accessibility was also studied and compared with other methods. The prediction accuracies are better than, or comparable to, those obtained by other methods such as neural networks, Bayesian classification, multiple linear regression, and information theory. In addition, our results further suggest that this system may be combined with other prediction methods to achieve more reliable results, and that the Support Vector Machine method is a very useful tool for biological sequence analysis. Proteins 2002;48:566–570. © 2002 Wiley‐Liss, Inc.
Inhibitor binding alters the directions of domain motions in HIV‐1 reverse transcriptase
Authors: Temiz N. Alpay , Bahar Ivet
Published: October 2002

Understanding the molecular mechanisms of HIV‐1 reverse transcriptase (RT) action and drug inhibition is essential for designing effective antiretroviral therapies. Although comparisons of the different crystal forms of RT give insights into the flexibility of different domains, a direct computational assessment of the effect of inhibitor binding on the collective dynamics of RT is lacking. A structure‐based approach is used here for exploring the dynamics of RT in unliganded and inhibitor‐bound forms. Non‐nucleoside RT inhibitors (NNRTI) are shown to interfere directly with the global hinge‐bending mechanism that controls the cooperative motions of the p66 fingers and thumb subdomains. The net effect of nevirapine binding is to change the direction of domain movements rather than suppress their mobilities. The second generation NNRTI, efavirenz, on the other hand, shows the stronger effect of simultaneously reorienting domain motions and obstructing the p66 thumb fluctuations. A second hinge site controlling the global rotational reorientations of the RNase H domain is identified, which could serve as a target for potential inhibitors of RNase H activity. Proteins 2002;49:61–70. © 2002 Wiley‐Liss, Inc.
Risks to the aquatic ecosystem from the application of Metarhizium anisopliae for locust control in Australia
Authors: Milner Richard J , Lim Richard P , Hunter David M
Published: October 2002

Laboratory tests of Metarhizium anisopliae var acridum Driver & Milner, at a dose of 1.3 × 106 conidia ml−1, had no adverse effects on nymphs of mayfly, Ulmerophlebia sp or 8‐week‐old fry of the rainbow fish, Melanotaenia duboulayi Castelnau. This dose was toxic to the cladoceran, Ceriodaphnia dubia Richard, causing 100% mortality in 48 h. When this test was repeated at doses of up to 6.7 × 103 conidia ml−1, there was only 5% mortality after 192 h. Spraying of artificial water sources with a very high dose of the fungus as an aqueous spray resulted in 80–130 conidia ml−1 at 15 cm depth in the first 24 h after spraying. The conidia rapidly settled out and were absent from the top 15 cm layer of water after about 50 h. A similar experiment using the oil formulation as used in field control resulted in a 2‐ to 20‐fold lower level of conidia in the water. Finally, sampling actual water sources in spray areas revealed a very low level of contamination of the water, with a maximum mean level of 29 conidia ml−1 in the first 24 h after treatment. Thus the level of conidia likely to enter water during control campaigns is a small fraction of that required to kill cladocerans, the only sensitive non‐target organism tested. It is concluded that the biopesticide is very unlikely to pose any hazard to aquatic organisms.

© 2002 Society of Chemical Industry
Authorship of drug industry trials
Authors: Senn Stephen
Published: October 2002

Viewpoint welcomes short papers expressing a personal opinion on matters of general interest to statisticians in the pharmaceutical industry. In this first issue Professor Stephen Senn shares his views on the authorship of drug industry trials. Copyright © 2002 John Wiley & Sons, Ltd.
Do statisticians count? A personal view
Authors: Grieve A. P.
Published: October 2002

The number of statisticians working in the pharmaceutical industry has risen 50‐fold since the formation of PSI in 1977. It would be comforting to think that the influence of statisticians within their companies has increased in a parallel fashion, however I do not believe that to be the case. In this paper I look at barriers which prevent statisticians contributing as much as they should and look at potentials solutions. Copyright © 2002 John Wiley & Sons, Ltd.
Psychopharmacological studies on Tragia involucrata root extract
Authors: Dhara A. K. , Pal S. , Nag Chaudhuri A. K.
Published: October 2002

The methanol fraction of the root extract of Tragia involucrata was investigated for psychopharmacological activity in rodents. It produced an alteration of behavioural pattern and a reduction in spontaneous motility. A significant potentiation of pentobarbitone‐induced sleep, a decrease of body temperature, suppression of the aggressive behaviour pattern and of the conditioned avoidance response (CAR) were observed with the fraction. These suggest that the methanol fraction of the T. involucrata root extract possesses significant central nervous system depressant action. Copyright © 2002 John Wiley & Sons, Ltd.
Activity of essential oils of three Micromeria species (Lamiaceae) against micromycetes and bacteria
Authors: Marinković B. , Marin P. D. , Knez̆ević‐Vukc̆ević J. , Soković M. D. , Brkić D.
Published: October 2002

The chemical composition of essential oils from three Micromeria species: M. dalmatica Benth., M. albanica (Griceb. ex K. Mal) Šilić and M. thymifolia (Scop.) Fritsch were investigated by GC and GC‐MS and their antibacterial and antifungal activities against seven fungal and six bacterial species were evaluated. Biological assays showed strong fungitoxicity of oils from all three Micromeria spp., particularly M. albanica, against all fungi tested. Essential oils of these species also exerted antibacterial effect against Streptococcus aureus, Escherichia coli, Bacillus subtilis and Micrococcus luteus at low concentrations. Higher concentrations of essential oil of M. albanica and M. dalmatica were active against Gram‐negative Pseudomonas aeruginosa, which could be due to the high content of piperitenone oxide. Copyright © 2002 John Wiley & Sons, Ltd.
Investigation on the hypoglycaemic effects of extracts of four Mexican medicinal plants in normal and Alloxan‐diabetic mice
Authors: Alarcon‐Aguilar F. J. , Roman‐Ramos R. , Flores‐Saenz J. L. , Aguirre‐Garcia F.
Published: October 2002

The hypoglycaemic activities of four water ethanol extracts (WEE) prepared from Bidens pilosa L., Salvia officinalis L., Psacalium peltatum H.B.K. (Cass) and Turnera diffusa Willd. were investigated in healthy and alloxan‐diabetic mice. The WEE of S. officinalis significantly reduced the blood glucose of fasting normal mice 120 (15.7%) and 240 min (30.2%) after intraperitoneal administration (p < 0.05). The WEE of P. peltatum and B. pilosa also significantly diminished glycaemia in healthy mice at 240 min (19.6% and 13.8%, respectively). In mildly diabetic mice, the WEE of P. peltatum lowered the basal blood glucose level 120 (16%) and 240 min (54%) after intraperitoneal administration (p < 0.05 and p < 0.01, respectively). The WEE of B. pilosa and S. officinalis also significantly diminished the hyperglycaemia in mildly diabetic mice at 240 mins (32.6% and 22.7%, respectively). The administration of these three extracts to animals with severe hyperglycaemia did not cause a significant decrease. The WEE of T. diffusa did not show any hypoglycaemic activity. Thus, three of the WEE studied conserved the hypoglycaemic activity originally detected in the traditional preparations of the studied antidiabetic plants. It appears that these extracts require the presence of insulin to show hypoglycaemic activity. Copyright © 2002 John Wiley & Sons, Ltd.
What's new?
Authors: Bohaychuk Wendy
Published: October 2002

The What's New? section in the Quality Assurance Journal aims to draw attention to items of importance to QA professionals. As there is a three‐month period between final submission of manuscripts and distribution of the journal, the items noted below will be at least three months old when you read them: for this issue, the entries arise from the period of 25 February 2002 to 31 May 2002. If you feel that there is any other new information that should be brought to the attention of readers, please let us know by e‐mailing: wbohaychuk@gcrpc.com Copyright © 2002 John Wiley & Sons, Ltd.
Investigation of the frequency‐dispersion effects on the Raman spectra of small polyenes
Authors: Quinet Olivier , Champagne Benoît
Published: October 2002

The time‐dependent Hartree–Fock scheme is applied for determining the frequency‐dependent Raman intensities of C2nH2n+2 molecules with n = 1–3. This analytic scheme, recently developed and implemented in the GAMESS program (Quinet, O.; Champagne, B. J Chem Phys 2001, 115, 6293), takes advantage of the 2n + 1 rule to express the polarizability derivatives in terms of first‐order derivatives. It is found that including frequency dispersion strongly modifies the intensity activy coefficients of many vibrational normal modes and therefore changes the aspect of the spectra. On the other hand, the depolarization ratio is much less frequency dependent. © 2002 Wiley Periodicals, Inc. Int J Quantum Chem, 2002
Molecular structure, conformational analysis and charge distribution of pralidoxime: Ab initio and DFT studies
Authors: Castro Alexandre T. , Figueroa‐Villar Jose D.
Published: October 2002

A detailed structural study of pralidoxime (2‐PAM), the main antidote against organophosphate intoxication, was performed using Hartree‐Fock, Möller–Plesset (MP2), and density functional theory (Becke, Lee, Yang, and Paar [B3LYP]) methods. Rotational barriers, equilibrium geometries, and charge distributions were calculated, showing important differences between the two forms available in physiological conditions, namely with the oxime group protonated or unprotonated. For the protonated form, conjugation between the side chain and the pyridinium ring, although present, has little importance, resulting in a flexible structure. On the other hand, the unprotonated form has a more rigid structure and a smaller charge density on the oxime oxygen. Contrary to the common belief, those results strongly suggest that it may be the protonated form of 2‐PAM, instead of the unprotonated form, that is responsible for the antidote activity of this compound. © 2002 Wiley Periodicals, Inc. Int J Quantum Chem, 2002