bluuebunny/crossref_metadata_2025 huggingface dataset:
Nature of water molecules in hydrogels based on a liquid crystalline cellulose derivative
Authors: Wojciechowski P. , Joachimiak A. , Halamus T.
Published: January 2004

The status and nature of water molecules in hydrogels with a liquid crystalline organization of the polymer network based on a biopolymer were investigated. Liquid crystalline (LC) hydrogels were obtained in situ by the photopolymerization of acrylic acid into the lyotropic liquid crystalline phase of (2‐hydroxypropyl)cellulose in a solvent mixture of water and acrylic acid. The photopolymerization of acrylic acid in the lyotropic liquid crystalline phase at room temperature gives a hydrogel in which liquid crystalline order and water are retained. The liquid crystalline hydrogel contains water, which originates from the composition of the lyotropic liquid crystalline phase, and may also contain water after immersion in liquid water. The water molecule characteristics were examined by means of differential scanning calorimetry, dielectric relaxation spectroscopy, and differential scanning calorimetry coupled with thermo‐optical measurements. The swelling data were obtained by using a weighing method. The investigations reveal the different nature of the two above‐mentioned water types. For the water from the composition of the lyotropic liquid crystalline phase, the phase transitions—typical for the bulk water—were not observed, in contract to the water after swelling of the liquid crystalline hydrogel in the liquid water. The results of the measurements suggest that water, which comes from the composition of the lyotropic liquid crystalline phase, forms—together with a polymer network—a microstructure, stabilized by this water. The water, after swelling of the LC hydrogel in the liquid water, is separated in the pores of the hydrogel and exhibits the phase transitions of the bulk water. Copyright © 2003 John Wiley & Sons, Ltd.
Lithocholic‐acid‐containing poly(ester–anhydride)s
Authors: Krasko Michal Y. , Ezra Aviva , Domb Abraham J.
Published: January 2004

New degradable poly(ester‐anhydride)s were prepared by melt polycondensation of poly(sebacic acid) (PSA), transesterified by different amounts (30–90%) of lithocholic acid (LCA), a natural hydroxy bile acid. Transesterification of PSA is a one‐pot reaction that starts with a high‐molecular‐weight polymer based on anhydride bonds and yields polymer based on random anhydride–ester bonds. A systematic study of the synthesis, characterization, degradation in vitro, drug release, and stability of these polymers was performed. Polymers with molecular weights (Mw) in the range of 12 000–115 000 and melting points in the range of 55–112 °C were obtained for 30–90% of lithocholic acid content. NMR and IR spectroscopic analyses indicate the formation of ester bonds in the polyanhydride backbone. The experimental results fit the calculated molecular weight, with the highest Mw obtained for a 4:6 PSA–LCA ratio. The study shows that some of these new degradable copolymers can be potentially used as carriers for the controlled release of drugs. Copyright © 2003 John Wiley & Sons, Ltd.
Examination of drug release from hydrogels
Authors: Erős István , Csóka Ildikó , Csányi Erzsébet , Takács‐Wormsdorff Tünde
Published: January 2004

The liberation of several important active agents was studied from hydrogels produced from new macromolecular substances. Liberation was examined with an in vitro method, with a Hanson's vertical diffusion cell. Polymers were used in an increasing concentration, while the quantity of active agents was constant. Several quantitative relationships were established after the examination of liberation from 240 drug‐containing gels. A power function was found between the concentration of the polymers and the quantity of the liberated active agents, while a logarithmic relationship existed between the viscosity of the gels and the extent of liberation. Interactions between the active agent and the vehicles can be inferred from the rheological functions as well as from the constants of the liberation versus concentration and liberation versus viscosity functions. Copyright © 2003 John Wiley & Sons, Ltd.
The risk of esophageal obstruction associated with an anti‐allergy medication (Claritin‐D® 24‐Hour—original formulation)
Authors: Manda Bharati , Drinkard Carol R. , Shatin Deborah , Graham David J.
Published: January 2004

Purpose

To investigate a possible increased risk of esophageal obstruction among users of loratadine and pseudoephedrine (Claritin‐D® 24‐Hour ‘C‐D 24’, the original, round, extended‐release formulation) compared to two other tablet formulations of loratadine.

Methods

Pharmacy data of 12 managed care plans were screened to identify users in the three groups from 1 September 1996 to 31 December 1998. Users with a medical claim following their first loratadine prescription (Index prescription) indicating an esophageal obstruction or endoscopic procedure were considered claims‐identified cases. Medical records were reviewed to validate case status.

Results

There were 233 901 users (61% female) and 245 claims‐identified cases occurring within 30 days after the first prescription. The incidence rate per 10 000 users of claims‐identified cases occurring on the Index prescription date was higher among C‐D 24 users (IR = 1.4) than Claritin® Regular (C‐R) users (IR = 0.07; p < 0.002) or Claritin‐D® 12‐Hour (C‐D 12) users (IR = 0.3; p > 0.05). Medical record review of 15 claims‐identified cases confirmed two cases of acute esophageal obstruction, both among C‐D 24 users.

Conclusions

Claims‐based analysis suggested an increased risk of endoscopic procedures on the Index date among C‐D 24 users compared to C‐R users. However, after medical record review, the study did not provide conclusive evidence of an association between C‐D 24 use and esophageal obstruction. This study highlights the importance of validating findings from claims data using medical records. Copyright © 2003 John Wiley & Sons, Ltd.
How well do patients report noncompliance with antihypertensive medications?: a comparison of self‐report versus filled prescriptions
Authors: Wang Philip S. , Benner Joshua S. , Glynn Robert J. , Winkelmayer Wolfgang C. , Mogun Helen , Avorn Jerry
Published: January 2004

Purpose

To address poor patient compliance with antihypertensives, clinicians and researchers need accurate measures of adherence with prescribed regimens. Although self‐reports are often the only means available in routine practice, their accuracy and agreement with other data sources remain questionable.

Methods

A telephone survey was conducted on 200 hypertensive patients treated with a single antihypertensive agent in a large health maintenance organization (HMO) or a Veterans Affairs medical center (VAMC) to obtain self‐reports of the frequency of missing antihypertensive therapy. We then analyzed records of all filled prescriptions to calculate the number of days that patients actually had antihypertensive medications available for use. Agreement between the two data sources was measured with correlation coefficients and kappa statistics. Logistic regression models were used to identify demographic, clinical and psychosocial correlates of overstating compliance.

Results

There was very poor agreement between self‐reported compliance and days actually covered by filled prescriptions (Spearman correlation coefficient = 0.15; 95%CI: 0.01, 0.28). Very poor agreement was also observed between a categorical measure of self‐reported compliance (ever vs. never missing a dose) and categories of actual compliance defined by filled prescriptions (< 80% vs > 80% of days covered; kappa = 0.12, 95%CI: −0.02, 0.26). Surprisingly, few factors were associated with inaccurate self‐reporting in either crude or adjusted analyses; fewer visits to health care providers was significantly associated with overstating compliance.

Conclusions

Compliance was markedly overstated in this sample of patients and few characteristics identified those who reported more versus less accurately. Clinicians and researchers who rely on self‐reports should be aware of these limits and should take steps to enhance their accuracy. Copyright © 2003 John Wiley & Sons, Ltd.
Infant vaccinations and childhood asthma among full‐term infants
Authors: Maher Julie E. , Mullooly John P. , Drew Lois , DeStefano Frank
Published: January 2004

Purpose

To determine if infant vaccinations are associated with childhood asthma among full‐term infants. The secondary objective was to describe relationships between characteristics of infant wheezing and childhood asthma.

Methods

We used baseline data from a study of infant wheezing that selected full‐term infants born into a health maintenance organization (HMO) during 1991–1994, continuously enrolled for at least 12 months and without perinatal pulmonary or other selected conditions. Information had been abstracted for infancy (0–18 months) regarding wheezing, vaccinations and asthma risk factors. Using automated data, we identified asthma cases in 1998 among those enrolled for at least 6 months during the year.

Results

A total of 1778 full‐term infants met our study criterion and 9% had asthma in 1998. Childhood asthma was not significantly associated with having received Hepatitis B vaccine or age at first Hepatitis B vaccine; number of whole‐cell pertussis, Haemophilis influenzae type b or oral polio vaccine doses; having received measles, mumps, rubella vaccine; or total number of vaccine doses combined. Childhood asthma was significantly associated with number of infant wheezing episodes.

Conclusions

Our findings do not support concerns that vaccines are associated with increased risk of asthma but confirm that frequency of infant wheezing is associated with childhood asthma. Copyright © 2003 John Wiley & Sons, Ltd.
Reduction in the therapeutic intensity of abortive migraine drug use during ACE inhibition therapy—a pilot study
Authors: Rahimtoola H. , Buurma H. , Tijssen C. C. , Leufkens H. G. , Egberts A. C. G.
Published: January 2004

Introduction

Since a few case reports have demonstrated some beneficial effects of angiotensin converting enzyme (ACE) inhibitors in migraine prevention, we were interested in studying the impact of ACE inhibitors and angiotensin II receptor antagonists (Ang II) on the consumption of specific abortive migraine drugs and, therefore, indirectly on the frequency of migraine attacks.

Methods

Data from a large prescription database involving 95 patients initiating a specific abortive migraine drug (ergotamine or a triptan) and subsequently treated with either an ACE inhibitor or angiotensin receptor antagonist (index group: ACE/Ang II) or diuretic (reference group) were analysed. The effects of ACE/Ang II inhibition as well as diuretic therapy on reducing the frequency of migraine attacks were assessed by measuring the mean consumption of abortive migraine drug use, in DDDs per month (‘therapeutic intensity’), before, during and after ACE/Ang II or diuretic therapy. A ‘therapeutic fluctuation intensity estimate’ of abortive migraine drug use for all patients was likewise calculated.

Results

On an individual level, the therapeutic intensity (TI) fluctuation estimate, ‘during’ relative to ‘before’ ACE diuretic therapy, was significantly larger for the ACE/Ang II group (62% reduction) than for the diuretic group (24% reduction) (p = 0.02). For patients who continued abortive migraine drug use during and after ACE/Ang II or diuretic therapy, a significantly larger reduction in this estimate was observed during ACE/Ang II inhibition (68.9%) compared to during diuretic therapy (10.5% increase) (p = 0.004). The TI fluctuation estimate, after relative to ‘during’, had increased by 50.3% after ACE/Ang II inhibition and had reduced by 22.2% after diuretic treatment (p = 0.1).

Conclusions

A clear reduction in the TI of abortive migraine drug use during the use of ACE inhibitors as compared to diuretic treatment was observed. Our findings may indirectly support a positive effect of ACE/Ang II inhibition on the frequency and severity of migraine attacks, as observed in other studies and reports. Copyright © 2003 John Wiley & Sons, Ltd.
Glow characterization in direct current plasma polymerization of trimethylsilane
Authors: Yu Q. S. , Huang C. , Yasuda H. K.
Published: January 2004

Plasma polymerization of trimethylsilane (TMS) was carried out in a direct current (dc) glow discharge and was investigated by optical photography and plasma diagnostic techniques including optical emission spectroscopy and residual gas analysis. The nature of the glow formed in TMS discharge, which deposited plasma polymers, was significantly different from that of a simple gas such as Ar. In an Ar discharge, the dominant glow was the well known negative glow, which developed at a distinctive distance from the cathode, whereas the cathode surface remained in the dark space. In strong contrast to this situation, in TMS dc discharge the dominant or primary glow was the cathode glow, which appeared at the cathode surface. At a similar location where the Ar negative glow appeared, a very feeble glow as a secondary glow was also observed in TMS glow discharge. The deposition results and plasma diagnosis data evidently indicated that in TMS glow discharge, the cathode glow resulted from the low‐energy electron‐impact dissociation of TMS molecules that creates polymerizable species, but the negative glow was related to nonpolymerizable species such as hydrogen atoms and molecules. In this article, the cathode glow formed in glow discharges of organic compounds was designated as the dissociation glow according to its underlying plasma reactions. © 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 42: 1042–1052, 2004
Synthesis and properties of novel Schiff base oligomers based on oligo‐4‐hydroxybenzaldehyde
Authors: Mart H. , Saçak M. , Yürük H. , Şahmetli̇oğlu E. , Vi̇layetoğlu A. R.
Published: January 2004

Condensation of oligo‐4‐hydroxybenzaldehyde with aniline, 2‐chloroaniline, 2‐aminophenol, 2‐aminotoluene, 4‐aminotoluene, and 4‐nitroaniline gave the corresponding Schiff base oligomers (OFAP, OKAP, OHAP, OOAP, OTAP, and ONAP, respectively). The products were characterized by 1H NMR, Fourier transform infrared, ultraviolet–visible, and elemental analyses. The number‐average molecular weight, mass‐average molecular weight, and polydispersity index (PDI) values of the Schiff base oligomers were determined. Thermogravimetric analysis was used to compare the thermal stability of the oligomers, which showed the Schiff base oligomers to be resistant to thermooxidative decomposition. Weight loss of 5% and 50% occurred at temperatures of 122 and 475 °C; for OFAP, at 118 and 453 °C; for OKAP, at 182 and 491 °C; for OHAP, at 150 and 452 °C; for OOAP, at 132 and 401 °C; for OTAP, and at 193 and 414 °C for ONAP. © 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 42: 1120–1125, 2004
Thermal behavior of poly(bisphenol A carbonate) in the presence of phosphorus compounds
Authors: Uozumi Toshiya , Kwon Tae Seok , Takeuchi Kazuhiko , Hayashi Teruyuki , Tanaka Masato
Published: January 2004

To clarify the interaction between poly(bisphenol A carbonate) (PBAC) and phosphorus compounds such as triphenylphosphine oxide (TPPO), triphenyl phosphate (TPP), and resorcinol bis(diphenyl phosphate) (RDP), PBAC was heated in the presence of these phosphorus compounds at 240 °C for 2 h, and the resulting polymers were analyzed by 1H NMR spectroscopy and gel permeation chromatography. When heated in the presence of TPPO, the PBAC sample decomposed extensively, resulting in a substantial decrease in molecular weight. On the other hand, thermal treatment in the presence of the phosphates increased the molecular weight. In both cases the molecular weight distribution became narrower. Thermal treatment of PBAC in the presence of both TPPO and TPP allowed us to control the molecular weight with a narrower distribution. © 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 42: 1069–1074, 2004
Very rapid copper‐mediated atom transfer radical polymerization of benzyl methacrylate at ambient temperature
Authors: Munirasu Selvaraj , Dhamodharan Raghavachari
Published: January 2004

The ability to do very rapid bulk atom transfer radical polymerization (ATRP) of benzyl methacrylate using a CuX/PMDETA complex at room temperature was demonstrated in this study. The experimental conditions required to synthesize low‐ and high‐molecular‐weight poly(benzyl methacrylate) with low polydispersity are reported here. The controlled/living nature of the polymerization was demonstrated through kinetic studies, and chain‐extension studies. © 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 42: 1053–1057, 2004
Synthesis of optically active polyurethanes by self‐polyaddition of tyrosine‐based monomers
Authors: Nagai Atsushi , Ishikawa Junichi , Kudo Hiroto , Endo Takeshi
Published: January 2004

The synthesis and self‐polyaddition of the optically active monomers I‐T(L)‐M and I‐T(D)‐M bearing both isocyanate and hydroxyl groups were examined. I‐T(L)‐M and I‐T(D)‐M were synthesized by reactions of L‐ and D‐tyrosine methyl ester, T(L)‐M and T(D)‐M, with di‐tert‐butyltricarbonate, respectively. The self‐polyaddition of I‐T(L)‐M and I‐T(D)‐M proceeded smoothly with triethylamine or tert‐butyllithium as the initiator in tetrahydrofuran, affording the optically active linear polyurethanes poly[I‐T(L)‐M] and poly[I‐T(D)‐M] with specific head‐to‐tail structures, where the number‐average molecular weights ranged from 10,000 to 20,000 in excellent yields. The optical properties suggested the idea that poly[I‐T(L)‐M] and poly[I‐T(D)‐M] should have some higher order structures. © 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 42: 1143–1153, 2004
Solvent effect on chain‐growth polycondensation for aromatic polyethers
Authors: Suzuki Yukimitsu , Hiraoka Shuichi , Yokoyama Akihiro , Yokozawa Tsutomu
Published: January 2004

The polycondensation of potassium 5‐cyano‐4‐fluoro‐2‐octylphenolate (1b) was carried out in the presence of 4‐fluoro‐4′‐trifluoromethylbenzophenone (2) as an initiator for chain‐growth polycondensation in a variety of solvents, and the chain‐growth nature of this polymerization was found to depend on the kind of solvent. In the polycondensation of 1b with 2 in sulfolane at 150 °C, the MALDI‐TOF mass spectra of poly1b showed only one series of peaks due to poly1b attached with the initiator 2 unit, and the 19F NMR spectra indicated that the ratios of the initiator unit to the end group were 1.0. Therefore, chain‐growth polycondensation occured in this condition. On the other hand, the polycondensation in THF, quinoline, DMI, tetraglyme at 150 °C gave poly1b with broad molecular weight distributions, and the MALDI‐TOF mass spectra showed two series of peaks resulting from both chain‐growth and step‐growth polycondensations. © 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 42: 1198–1207, 2004
Preparation and characterization of chiral polyacrylates end‐capped with bornyl groups in the side chains
Authors: Liu Jui‐Hsiang , Hsieh Ching‐Dong , Wang Hong‐Yu
Published: January 2004

Chiral polyacrylates with bornyl end‐capped side chains with four kinds of mesogenic moieties (azobenzene, biphenyl, benzoyloxy biphenyl, and phenyl benzoate) were prepared. The phase properties of the polymers were investigated with X‐ray diffraction, differential scanning calorimetry, and polarizing optical microscopy. The thermogravimetric characteristics, the glass‐transition temperatures and weight‐average molecular weights, of the homopolymers were evaluated. The optical properties of the synthesized polymers in diluted solutions and in the thin‐film state were also evaluated. The optical behavior of the composite films upon photoirradiation was investigated through the change in the transmittance of the probe light triggered by ultraviolet (365‐nm) irradiation. Ultraviolet irradiation and heat treatment caused a reversible intensity change of the probe light at λ = 400 nm. The shrinkage of the photoisomerization of the composite films was also investigated with atomic force microscopy. A spot contraction appeared on the surface when it was irradiated with a laser light spot. The contraction was recovered by heat treatment at 80 °C for 10 min. © 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 42: 1075–1092, 2004
Tropone‐containing π‐conjugated polymers: Annulation of tropone onto benzene ring in the conjugated polymer
Authors: Nishioka Naomi , Takagi Koji , Kinoshita Takatoshi , Kunisada Hideo , Yuki Yasuo
Published: January 2004

Tropone‐fused, various π‐conjugated polymers (P2–P5) were synthesized by the palladium‐catalyzed coupling reaction of 1,4‐dibromo‐6,8‐dimethyl‐7H‐benzocyclohepten‐7‐one with aromatic divinyl, diboronic acid, and diethynyl compounds. The molecular orbital calculation of the model compounds was performed to discuss effective conjugation length of the repeating unit of the polymers. The absorption spectra of phenylenevinylene‐type polymers shifted to longer wavelengths than the model compounds by about 60 nm. They exhibited green fluorescence [λmax(em) = 544 and 561 nm]. The absorption spectrum of a phenylene‐type polymer blueshifted by 10 nm; however, that of a phenyleneethynylene‐type polymer redshifted by 83 nm as compared with their model compounds. They showed fluorescence with peak maxima at 457 and 489 nm, respectively. As a result, the absorption spectra of phenylene‐ and phenylenevinylene‐type polymers blueshifted, but that of a phenyleneethynylene‐type polymer redshifted by the annulation of tropone onto a benzene ring in the conjugated polymer. © 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 42: 1208–1215, 2004
Dendritic homopolymers and block copolymers: Tuning the morphology and properties
Authors: Trollsås Mikael , Atthoff Björn , Claesson Hans , Hedrick James L.
Published: January 2004

The synthesis and characterization of dendritic homopolymers and block copolymers of ϵ‐caprolactone and lactide (L‐lactide and racemic lactide) were performed with multifunctional initiators in combination with living polymerization and the selective placement of branching junctures in a divergent growth strategy. A hexahydroxy‐functional 2,2‐bis(hydroxymethyl) propionic acid derivative was used as an initiator for the stannous‐2‐ethylhexanoate‐catalyzed living ring‐opening polymerization of ϵ‐caprolactone, L‐lactide, and racemic L,D‐lactide. Branching junctions at the chain ends were introduced with benzylidene‐protected 2,2‐bis(hydroxymethyl) propionic acid. Subsequent generations were then polymerized, after deprotection, from these star‐shaped macroinitiators. Successive chain end capping and initiation produced three generations of polymers with molecular weights in excess of 130,000 g/mol and narrow polydispersities (<1.20). It was possible to prepare diblock and triblock copolymers with phase‐separated morphologies, and with L‐lactide or D,L‐lactide, semicrystalline and amorphous morphologies were demonstrated. The polymers were characterized by 1H NMR, 13C NMR, size exclusion chromatography, and differential scanning calorimetry. The compositions of the block copolymers and the conformational structures of the optically active polymers were also confirmed by optical rotation measurements. © 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 42: 1174–1188, 2004
Synthesis and properties of soluble trifluoromethyl‐substituted polyimides containing laterally attached p‐Terphenyls
Authors: Hsiao Sheng‐Huei , Chang Yu‐Hui
Published: January 2004

A new fluorinated diamine monomer, 2′,5′‐bis(4‐amino‐2‐trifluoromethylphenoxy)‐p‐terphenyl, was synthesized from the chloro‐displacement of 2‐chloro‐5‐nitrobenzotrifluoride with the potassium phenolate of 2,5‐diphenylhydroquinone, followed by hydrazine palladium‐catalyzed reduction. A series of trifluoromethyl‐substituted polyimides containing flexible ether linkages and laterally attached side rods were synthesized from the diamine with various aromatic dianhydrides via a conventional two‐step process. The inherent viscosities of the poly(amic acid) precursors were 0.84–1.26 dL/g. All the polyimides afforded flexible and tough films. The use of 4,4′‐oxydiphthalic anhydride and 2,2′‐bis(3,4‐dicarboxyphenyl)hexafluoropropane dianhydride produced essentially colorless polyimide films. Most of the polyimides revealed an excellent solubility in many organic solvents. The glass‐transition temperatures of these polyimides were recorded between 254 and 299 °C by differential scanning calorimetry, and the softening temperatures of the polymer films stayed in the range of 253–300 °C according to thermomechanical analysis. The polyimides did not show significant decomposition before 500 °C in air or under nitrogen. These polyimides also showed low dielectric constants (2.83–3.34 at 1 MHz) and low moisture absorption (0.4–2.2%). For a comparative study, a series of analogous polyimides based on the nonfluorinated diamine 2′,5′‐bis(4‐aminophenoxy)‐p‐terphenyl were also prepared and characterized. © 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 42: 1255–1271, 2004
Radiochemical aging of ethylene–propylene–diene monomer elastomers. I. Mechanism of degradation under inert atmosphere
Authors: Rivaton A. , Cambon S. , Gardette J.‐L.
Published: January 2004

This article is devoted to the study of electron‐beam‐induced degradation under argon atmosphere of an ethylene–propylene–diene monomer (EPDM, based on 5‐ethylidene 2‐norbornene) and an ethylene–propylene rubber (EPR) containing the same molar ratio of ethylene/propylene. The chemical structure modifications of polymeric samples were analyzed by ultraviolet–visible and IR spectroscopies. Crosslinking reactions were deduced by measuring the changes in gel fraction and the degree of swelling in n‐heptane. Irradiation of EPDM and EPR created trans‐vinylene, vinyl, vinylidene, and dienic‐type unsaturations. The radiochemical yields for unsaturation formations in EPDM and EPR were similar. Degradation also involved crosslinking and the production of molecular hydrogen. The comparison between EPDM and EPR showed that the diene (in which a double bond is consumed with a high radiochemical yield) contributes to the increase in rate and intermolecular bridges density. Mechanisms are proposed to account for the main routes of EPDM degradation. © 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 42: 1239–1248, 2004
Illusions in advanced cancer: The effect of belief systems and attitudes on quality of life
Authors: Beadle G.F. , Yates P.M. , Najman J.M. , Clavarino A. , Thomson D. , Williams G. , Kenny L. , Roberts S. , Mason B. , Schlect D.
Published: January 2004

Patients with advanced cancer frequently express positive attitudes and can be unduly optimistic about the potential benefits of treatment. In order to evaluate an illusory domain in the context of advanced cancer, we developed a scale of will to live and characterized the beliefs that patients held about the curability of their cancer, and how committed they were to using alternative treatments. A measure of quality of life was used as the dependent variable in order to assess the association between these attributes. After a preliminary exploration confirmed the presence of an illusory domain, these concepts were prospectively tested in 149 ambulant patients with advanced cancer who attended for palliative systemic treatment, radiation treatment or supportive care. The scale of global quality of life was reliable (Cronbach's alpha coefficient 0.72). The distribution of the scores of will to live was skewed, with no respondent scoring poorly, and the scale was reliable (Cronbach's alpha coefficient 0.82). The scale of belief in curability showed diverse beliefs. In some cases, there was a discrepancy between respondents' beliefs in curability and what they believed to be the report by their doctors. There was also an association between a committed use of alternative treatments and a belief in the curability of the cancer (p<0.001). In a multiple regression analysis, both will to live and performance status remained associated with better quality of life scores after adjustment for other relevant variables (p<0.05 and <0.001, respectively). These results suggest that positive illusory beliefs can be measured and are an important component of adaption for some patients with advanced cancer. Furthermore, this illusory domain may influence the perception and measurement of quality of life. Copyright © 2003 John Wiley & Sons, Ltd.
Psychosocial functioning in women who have undergone bilateral prophylactic mastectomy
Authors: Metcalfe Kelly A. , Esplen Mary Jane , Goel Vivek , Narod Steven A.
Published: January 2004

The purpose of this study was to determine the current psychosocial functioning of women who had previously had a bilateral prophylactic mastectomy. Women in the province of Ontario who had undergone prophylactic mastectomy between 1991 and 2000 were asked to complete questionnaires that assessed psychological distress, sexual activity, overall satisfaction with decision to have a prophylactic mastectomy, and body image. Ninety‐seven percent of the women were satisfied with their decision to have a prophylactic mastectomy, but young women (<50 years) were less likely to report satisfaction than older women (p=0.001). Women with a strong family history of breast cancer or a BRCA1 or BRCA2 mutation experienced more cancer‐related distress than those with a limited family history. Women who had reconstruction following mastectomy reported higher levels of satisfaction with general body shape and appearance than those without reconstruction. In conclusion, the majority of women were satisfied with their decision to undergo prophylactic mastectomy and were not experiencing abnormal levels of psychological distress, low levels of sexual activity, or difficulties with body image. Copyright © 2003 John Wiley & Sons, Ltd.
Myosin flexibility: Structural domains and collective vibrations
Authors: Navizet Isabelle , Lavery Richard , Jernigan Robert L.
Published: January 2004

The movement of the myosin motor along an actin filament involves a directed conformational change within the cross‐bridge formed between the protein and the filament. Despite the structural data that has been obtained on this system, little is known of the mechanics of this conformational change. We have used existing crystallographic structures of three conformations of the myosin head, containing the motor domain and the lever arm, for structural comparisons and mechanical studies with a coarse‐grained elastic network model. The results enable us to define structurally conserved domains within the protein and to better understand myosin flexibility. Notably they point to the role of the light chains in rigidifying the lever arm and to changes in flexibility as a consequence of nucleotide binding. Proteins 2004;54:000–000. © 2003 Wiley‐Liss, Inc.
The number of protein folds and their distribution over families in nature
Authors: Liu Xinsheng , Fan Ke , Wang Wei
Published: January 2004

Currently, of the 106 known protein sequences, only about 104 structures have been solved. Based on homologies and similarities, proteins are grouped into different families in which each has a structural prototype, namely, the fold, and some share the same folds. However, the total number of folds and families, and furthermore, the distribution of folds over families in nature, are still an enigma. Here, we report a study on the distribution of folds over families and the total number of folds in nature, using a maximum probability principle and the moment method of estimation. A quadratic relation between the numbers of families and folds is found for the number of families in an interval from 6000 to 30,000. For example, about 2700 folds for 23,100 families are obtained, among them about 33 superfolds, including more than 100 families each, and the largest superfold comprises about 800 families. Our results suggest that although the majority of folds have only a single family per fold, a considerably larger number of folds include many more families each than in the database, and the distribution of folds over families in nature differs markedly from the sampled distribution. The long tail of fold distribution is first estimated in this article. The results fit the data for different versions of the structural classification of proteins (SCOP) excellently, and the goodness‐of‐fit tests strongly support the results. In addition, the method of directly “enlarging” the sample to the population may be useful in inferring distributions of species in different fields. Proteins 2004;54:000–000. © 2003 Wiley‐Liss, Inc.
Splice variants: A homology modeling approach
Authors: Furnham Nicholas , Ruffle Stuart , Southan Christopher
Published: January 2004

Splice variants play an important role within the cell in both increasing the proteome diversity and in cellular function. Splice variants are also associated with disease states and may play a role in their etiology. Information about splice variants has, until now, mostly been derived from the primary transcript or through cellular studies. In this study information from the transcript and other studies is combined with tertiary structure information derived from homology models. Through this method we have determined that it is possible to effectively model splice variants. Forty models of splice variants for fourteen proteins were produced. Analysis of the models shows that deletions produce superior model validation values. Additions to sequences where there is little homology become increasingly difficult to model with increasing sequence length. Many of the splicing events are associated with post‐translational modification either in the N‐terminal region by changing the signal peptide or by affecting the number or availability of glycosylation sites. Often the alternative exon combinations are associated with loss or gain of whole structural units, as opposed to just changing small loop regions. Losing part of the secondary structure may destabilize neighboring parts of the same secondary structure. Detailed analysis is given of four biomedically relevant proteins (Beta‐site Amyloid Precursor Protein Cleaving enzyme (BACE), Interleukin‐4, Frataxin and Hereditary hemochromatosis protein) and their associated splice variant models. The visualization of these possible structures provides new insights about their functionality and the possible etiology of associated diseases. Proteins 2004;54:000–000. © 2003 Wiley‐Liss, Inc.
Aromatic side‐chain interactions in proteins: Near‐ and far‐sequence Tyr‐X pairs
Authors: Meurisse Rita , Brasseur Robert , Thomas Annick
Published: January 2004

In the present study, an extensive analysis of the aromatic Tyr‐X interactions is performed on a data set of 593 PDB structures, X being Phe, His, Tyr, and Trp. The nonredundant Tyr‐X pairs (2645) were retained and separated by both the residue distance in the sequence and the secondary structures they bridge. Similar to the Phe‐X and His‐X pairs, the far‐sequence Tyr‐X pairs (X partner > five apart in the sequence: 74%) show comparable secondary structures and conformers for either type of X partner, in contrast with the near‐sequence Tyr‐X pairs (26%). As the Phe‐X pairs, the near‐sequence Tyr‐X pairs stabilize secondary structures, mainly the α‐ helices (positions 1, 3, and 4) and the β‐strands (position 2). Like the Phe‐X and His‐X pairs, most far‐sequence Tyr‐X pairs (34%) bridge β‐strands and only 11% bridge helices. As for the Phe‐X and the His‐X pairs, the X partners of the far‐sequence Tyr‐X pairs are frequently “above” the tyrosine ring with tilted and normal rings, whereas the X partner of the near‐sequence Tyr‐X pairs gradually moves from the “aside” to the “above” location, together with a progressive decrease of normal and increase of parallel rings, respectively. Unlike the His‐X pairs, the interactions of the hetroatom in Tyr‐X pairs are only favored with a sequence position +4 and over, owing to the spatial accessibility of the heteroatom. Proteins 2004;54:000–000. © 2003 Wiley‐Liss, Inc.
Analysis of the products of genes encompassed by the theoretically predicted pathogenicity islands of Mycobacterium tuberculosis and Mycobacterium bovis
Authors: Zubrzycki Igor Z.
Published: January 2004

Sequencing of the genomes of Mycobacterium tuberculosis and Mycobacterium bovis provides a unique opportunity to study the biology of these pathogens on the genomic level. The computational detection of anomalous gene clusters such as those encompassed by pathogenicity islands allows for a narrowing of the study into well‐defined groups of genes. Pathogenicity islands of M. tuberculosis (strains H37Rv and CDC1551) as well as M. bovis genomes comprise a group of genes encoding proteins that have been shown to be of immunological importance. The cross‐genomic comparison (M. tuberculosis vs M. bovis) resulted in the elucidation of unique proteins in M. tuberculosis. These proteins may play a significant role in the host recognition process. Proteins 2004; 54:000–000. © 2003 Wiley‐Liss, Inc.
A pharmacophore docking algorithm and its application to the cross‐docking of 18 HIV‐NNRTI's in their binding pockets
Authors: Daeyaert Frits , de Jonge Marc , Heeres Jan , Koymans Luc , Lewi Paul , Vinkers Maarten H. , Janssen Paul A.J.
Published: January 2004

The docking of small molecules into the binding site of a target protein is an important but difficult step in structure‐based drug design. The performance of a docking algorithm is usually evaluated by re‐docking ligands into their native binding sites. We have explored the cross‐docking of 18 HIV‐NNRTIs (non‐nucleoside inhibitors of HIV reverse transcriptase) of which the ligand–protein structure has been determined: each of the 18 ligands was docked into each of the 18 binding sites. The docking algorithms studied are an energy‐based simulated annealing algorithm and a novel pharmacophore docking algorithm. It turns out that the energy‐based docking of the ligands into non‐native pockets is far less successful than the docking into their native pockets. The results can be improved by using explicit pharmacophore information, and by docking a ligand into a panel of protein structures and selecting the ligand–proteincombination with the lowest interaction energy as the final result. Proteins 2004;54:000–000. © 2003 Wiley‐Liss, Inc.
Efficient methods for filtering and ranking fragments for the prediction of structurally variable regions in proteins
Authors: Heuser Philipp , Wohlfahrt Gerd , Schomburg Dietmar
Published: January 2004

The prediction of protein 3D structures close to insertions and deletions or, more generally, loop prediction, is still one of the major challenges in homology modeling projects. In this article, we developed ranking criteria and selection filters to improve knowledge‐based loop predictions. These criteria were developed and optimized for a test data set containing 678 insertions and deletions. The examples are, in principle, predictable from the used loop database with an RMSD < 1 Å and represent realistic modeling situations. Four noncorrelated criteria for the selection of fragments are evaluated. A fast prefilter compares the distance between the anchor groups in the template protein with the stems of the fragments. The RMSD of the anchor groups is used for fitting and ranking of the selected loop candidates. After fitting, repulsive close contacts of loop candidates with the template protein are used for filtering, and fragments with backbone torsion angles, which are unfavorable according to a knowledge‐based potential, are eliminated. By the combined application of these filter criteria to the test set, it was possible to increase the percentage of predictions with a global RMSD < 1 Å to over 50% among the first five ranks, with average global RMSD values for the first rank candidate that are between 1.3 and 2.2 Å for different loop lengths. Compared to other examples described in the literature, our large numbers of test cases are not self‐predictions, where loops are placed in a protein after a peptide loop has been cut out, but are attempts to predict structural changes that occur in evolution when a protein is affected by insertions and deletions. Proteins 2004;54:000–000. © 2003 Wiley‐Liss, Inc.
Three acidic residues are at the active site of a β‐propeller architecture in glycoside hydrolase families 32, 43, 62, and 68
Authors: Pons Tirso , Naumoff Daniil G. , Martínez‐Fleites Carlos , Hernández Lázaro
Published: January 2004

Multiple‐sequence alignment of glycoside hydrolase (GH) families 32, 43, 62, and 68 revealed three conserved blocks, each containing an acidic residue at an equivalent position in all the enzymes. A detailed analysis of the site‐directed mutations so far performed on invertases (GH32), arabinanases (GH43), and bacterial fructosyltransferases (GH68) indicated a direct implication of the conserved residues Asp/Glu (block I), Asp (block II), and Glu (block III) in substrate binding and hydrolysis. These residues are close in space in the 5‐bladed β‐propeller fold determined for Cellvibrio japonicus α‐L‐arabinanase Arb43A [Nurizzo et al., Nat Struct Biol 2002;9:665–668] and Bacillus subtilis endo‐1,5‐α‐L‐arabinanase. A sequence–structure compatibility search using 3D‐PSSM, mGenTHREADER, INBGU, and SAM‐T02 programs predicted indistinctly the 5‐bladed β‐propeller fold of Arb43A and the 6‐bladed β‐propeller fold of sialidase/neuraminidase (GH33, GH34, and GH83) as the most reliable topologies for GH families 32, 62, and 68. We conclude that the identified acidic residues are located at the active site of a β‐propeller architecture in GH32, GH43, GH62, and GH68, operating with a canonical reaction mechanism of either inversion (GH43 and likely GH62) or retention (GH32 and GH68) of the anomeric configuration. Also, we propose that the β‐propeller architecture accommodates distinct binding sites for the acceptor saccharide in glycosyl transfer reaction. Proteins 2004. © 2003 Wiley‐Liss, Inc.
Solution structure of the highly acidic protein HI1450 from Haemophilus influenzae, a putative double‐stranded DNA mimic
Authors: Parsons Lisa M. , Yeh Deok Cheon , Orban John
Published: January 2004

The solution structure of the acidic protein HI1450 from Haemophilus influenzae has been determined by NMR spectroscopy. HI1450 has homologues in ten other bacterial species including Escherichia coli, Vibrio cholerae, and Yersinia pestis but there are no functional assignments for any members of the family. Thirty‐one of the amino acids in this 107‐residue protein are aspartates or glutamates, contributing to an unusually low pI of 3.72. The secondary structure elements are arranged in an α‐α‐β‐β‐β‐β order with the two alpha helices packed against the same side of an anti‐parallel four‐stranded beta meander. Two large loops, one between β1 and β2 and the other between β2 and β3 bend almost perpendicularly across the β‐strands in opposite directions on the non‐helical side of the β‐sheet to form a conserved hydrophobic cavity. The HI1450 structure has some similarities to the structure of the double‐stranded DNA (dsDNA) mimic uracil DNA glycosylase inhibitor (Ugi) including the distribution of surface charges and the position of the hydrophobic cavity. Based on these similarities, as well as having a comparable molecular surface to dsDNA, we propose that HI1450 may function as a dsDNA mimic in order to inhibit or regulate an as yet unidentified dsDNA binding protein. Proteins 2004;54:000–000. © 2003 Wiley‐Liss, Inc.
Predicting peptide binding to MHC pockets via molecular modeling, implicit solvation, and global optimization
Authors: Schafroth Heather D. , Floudas Christodoulos A.
Published: January 2004

Development of a computational prediction method based on molecular modeling, global optimization, and implicit solvation has produced accurate structure and relative binding affinity predictions for peptide amino acids binding to five pockets of the MHC molecule HLA‐DRB1*0101. Because peptide binding to MHC molecules is essential to many immune responses, development of such a method for understanding and predicting the forces that drive binding is crucial for pharmaceutical design and disease treatment. Underlying the development of this prediction method are two hypotheses. The first is that pockets formed by the peptide binding groove of MHC molecules are independent, separating the prediction of peptide amino acids that bind within individual pockets from those that bind between pockets. The second hypothesis is that the native state of a system composed of an amino acid bound to a protein pocket corresponds to the system's lowest free energy. The prediction method developed from these hypotheses uses atomistic‐level modeling, deterministic global optimization, and three methods of implicit solvation: solvent‐accessible area, solvent‐accessible volume, and Poisson–Boltzmann electrostatics. The method predicts relative binding affinities of peptide amino acids for pockets of HLA‐DRB1*0101 by determining computationally an amino acid's global minimum energy conformation. Prediction results from the method are in agreement with X‐ray crystallography data and experimental binding assays. Proteins 2004;54:000–000. © 2003 Wiley‐Liss, Inc.
Comparison of backbone dynamics of monomeric and domain‐swapped stefin A
Authors: Japelj Boštjan , Waltho Jonathan P. , Jerala Roman
Published: January 2004

Three‐dimensional domain swapping has been observed in increasing number of proteins and has been implicated in the initial stages of protein aggregation, including that of the cystatins. Stefin A folds as a monomer under native conditions, while under some denaturing conditions domain‐swapped dimer is formed. We have determined the backbone dynamics of the monomeric and domain‐swapped dimeric forms of stefin A by 15N relaxation using a model‐free approach. The overall correlation times of the molecules were determined to be 4.6 ± 0.1 ns and 9.2 ± 0.2 ns for the monomer and the dimer, respectively. In the monomer, decreased order parameters indicate an increased mobility for the N‐terminal trunk, the first and the second binding loops. At the opposite side of the molecule, the loop connecting the α‐helix with strand B, the beginning of strand B and the loop connecting strands C and D show increased localized mobility. In the domain‐swapped dimer, a distinctive feature of the structure is the concatenation of strands B and C into a single long β‐strand. The newly formed linker region between strands B and C, which substitutes for the first binding loop in the monomer, has order parameters typical for the remainder of the β‐strands. Thus, the interaction between subunits that occurs on domain‐swapping has consequences for the dynamics of the protein at long‐range from the site of conformational change, where an increased rigidity in the newly formed linker region is accompanied by an increased mobility of loops remote from that site. Proteins 2004. © 2004 Wiley‐Liss, Inc.