bluuebunny/crossref_metadata_2025 huggingface dataset:
A pan‐European epidemiologic study of insulin injection technique in patients with diabetes
Authors: Strauss Kenneth , Gols Heidi De , Hannet Irene , Partanen Tuula‐Maria , Frid Anders
Published: August 2002

Aim.

A large pan‐European epidemiologic survey of insulin injection techniques was performed in order to determine the epidemiologic profile by centre, country and continent of major issues surrounding insulin injection.

Methods.

European insulin‐injecting, type 1 or 2 diabetes patients, using insulin for at least 6 months via an insulin pen or syringe; 22 sites in seven countries, 1002 patients in total, 51% female, 58% type 1.

Results.

Nearly 70% of patients inject using a pinch‐up and this practice is associated with improved HbA1c. Thirty per cent of patients reported having lipohypertrophy. Concurrent nurse evaluation found the prevalence to be 27%. Independent risk factors for lipohypertrophy were found to be failure by the patients to check injection sites regularly, failure to rotate sites and longer duration of DM. Less than 50% of patients reported that they were taught about lipohypertrophy. Needles were used 3.3 times on average in Europe, with wide variation by country. Male sex, type 1 diabetics, a high daily number of injections and the use of the 12.7 mm length needle were factors associated with high needle reuse. Needle reuse, even more than once, increased the risk of lipohypertrophy by 31%. Nearly half of patients dispose of their needles directly into the trash after protecting the needle (recapping or clipping). Alarmingly, 22% dispose directly into the trash without protection.

Conclusion.

There is a considerable way to go in ensuring optimal insulin injection practices. The issues raised by this study must be addressed by focused and intensive HCP efforts. Copyright © 2002 John Wiley & Sons, Ltd.
A comparison of measures of disproportionality for signal detection in spontaneous reporting systems for adverse drug reactions
Authors: van Puijenbroek Eugéne P. , Bate Andrew , Leufkens Hubert G. M. , Lindquist Marie , Orre Roland , Egberts Antoine C. G.
Published: August 2002

Purpose

A continuous systematic review of all combinations of drugs and suspected adverse reactions (ADRs) reported to a spontaneous reporting system, is necessary to optimize signal detection. To focus attention of human reviewers, quantitative procedures can be used to sift data in different ways. In various centres, different measures are used to quantify the extent to which an ADR is reported disproportionally to a certain drug compared to the generality of the database. The objective of this study is to examine the level of concordance of the various estimates to the measure used by the WHO Collaborating Centre for International ADR monitoring, the information component (IC), when applied to the dataset of the Netherlands Pharmacovigilance Foundation Lareb.

Methods

The Reporting Odds Ratio−1.96 standard errors (SE), proportional reporting ratio−1.96 SE, Yule's Q−1.96 SE, the Poisson probability and Chi‐square test of all 17 330 combinations were compared with the IC minus 2 standard deviations. Additionally, the concordance of the various tests, in respect to the number of reports per combination, was examined.

Results

In general, sensitivity was high in respect to the reference measure when a combination of point‐ and precision estimate was used. The concordance increased dramatically when the number of reports per combination increased.

Conclusion

This study shows that the different measures used are broadly comparable when four or more cases per combination have been collected. Copyright © 2001 John Wiley & Sons, Ltd.
Drug prescribing patterns in Parkinson's disease: a pharmacoepidemiological survey in a cohort of ambulatory patients
Authors: Leoni Olivia , Martignoni Emilia , Cosentino Marco , Michielotto Donatella , Calandrella Daniela , Zangaglia Roberta , Riboldazzi Giulio , Oria Cristina , Lecchini Sergio , Nappi Giuseppe , Frigo Gianmario
Published: August 2002

Purpose

Drug treatment of idiopathic Parkinson's disease (IPD) is a difficult task, and comorbidity and comedication add to its complexity. Since in IPD there is little information about drug use, this study investigated drug prescribing and indications in IPD patients.

Methods

From June 1997 to April 1998, a cross‐sectional survey of IPD outpatients was performed and demographic and clinical data and information about drug treatments was collected and analysed.

Results

In the 130 IPD patients included in the study, anti‐Parkinson drug (APD) prescriptions increased with disease duration and severity. Levodopa was most frequently used, followed by dopamine agonists and anticholinergic agents. Levodopa with other APDs was given to older patients with later IPD onset. Prescriptions of drugs for other indications (non‐APDs) were given to 80.8% of the patients and their number increased with patient age. Non‐APD prescriptions concerned mainly the circulatory system, mental disorders, the musculo‐skeletal system and the digestive system. Prescriptions for indications corresponding to secondary symptoms that often complicate IPD increased with patient age and also with IPD duration.

Conclusion

In IPD patients, disease duration and severity and patient age seem to be major determinants of drug use. Indications for drug prescription suggest that main comorbidity includes neuropsychiatric, circulatory, musculo‐skeletal and digestive disorders. Analysis of prescribing patterns in IPD can provide a readily accessible indirect indicator of patient health status for both health services and epidemiologic research purposes. Copyright © 2002 John Wiley & Sons, Ltd.
Reaction kinetics of graft copolymerization and thermochemical studies of the degradation of poly(vinyl alcohol) graft copolymer
Authors: Aggour Yassin A
Published: August 2002

Poly(vinyl alcohol) (PVA) is a water‐soluble and biomedical polymer. 2‐Acrylamido‐2‐methyl‐1‐propanesulfonic acid was grafted onto PVA using ammonium persulfate as radical initiator. The influences of synthesis conditions such as temperature, concentrations of initiator, PVA and monomer were investigated. Both the initial rate of grafting and the final percentage of grafting were increased by an increase in reaction temperature. The reaction kinetics were studied to determine the rate constants of the first‐order reactions. An activation energy of 16.3 kJ mol−1 was found for the grafting reaction. The graft copolymers were characterized by IR and intrinsic viscosity measurements. A proposed mechanism of the grafting reaction is discussed. Kinetics of the thermal degradation were studied using a thermogravimetric method and the order of thermal stabilities are given. The apparent activation thermodynamic parameters, Ea, ΔH*, ΔS* and ΔG* were determined and correlated to the thermal stabilities of the homo‐ and grafted polymers.

© 2001 Society of Chemical Industry
Dispersion polymerization of aniline using hydroxypropylcellulose as stabilizer: role of rate of polymerization
Authors: Chattopadhyay Dipankar , Chakraborty Mukut , Mandal Broja M
Published: August 2002

Hydroxypropylcellulose (HPC) has been used as a steric stabilizer for preparing polyaniline dispersions using the route of oxidative dispersion polymerization of aniline. Using strongly acidic conditions (1 mol l−1 HCl), low temperature of about 2 °C and a concentration of aniline as low as 0.5%, ammonium peroxodisulfate at 1.25% and hydroxypropylcellulose concentrations at 0.5–1 g d l−1, unstable dispersions were obtained not only in water but also in aqueous alcohols (ethanol and methanol) up to at least 70 vol% alcohol. In contrast, dispersions that remained stable for at least 72 h were obtained when the alcohol concentration of the medium was as high as about 80 vol%. Kinetic studies of the polymerization systems suggested that success in the latter case was due to a lowering of the rate of polymerization. Transmission electron microscopy studies showed that dispersion particles prepared in 80 vol% alcohol media are spherical in shape and their diameter decreases with increasing stabilizer concentration. However, a change of morphology from spherical to aggregated needle‐shaped was observed when the rate was increased by increasing the aniline concentration from 0.5% to 0.75% g d l−1 in the above recipe. The aggregated particles were found to be broken down to spherical nanoparticles when the as‐prepared dispersions were sonicated for about 30 min. The sonicated dispersion on drying showed the presence of fractal clusters of polyaniline particles in the dried film. The fractal dimension was determined to be 1.77 which agreed well with the theoretical value determined by computer simulation based on a diffusion limited cluster–cluster aggregation model in three dimensions.

© 2001 Society of Chemical Industry
Structure and properties of poly(vinyl alcohol)/κ‐carrageenan blends
Authors: Tanaka Toshihisa , Lu Tong , Yuasa Shingo , Yamaura Kazuo
Published: August 2002

Blends of a commercial atactic poly(vinyl alcohol) (a‐PVA) derived from vinyl acetate and κ‐carrageenan were prepared by mixing the aqueous solutions of both samples. Blend films prepared by casting were transparent. In the DSC curves of the blend films, the endothermic peaks shifted to lower temperature with an increase of the content of κ‐carrageenan. The Young's modulus and the strength at break increased with an increase of the content of a‐PVA. As the standing temperature of the blend solutions decreased, the gelation region increased also at high content of carrageenan. In the amorphous regions of blend films, a‐PVA and κ‐carrageenan were miscible.

© 2001 Society of Chemical Industry
Externalizing behavior problems in young children: Contributing factors and early intervention
Authors: Stormont Melissa
Published: August 2002

Early intervention should begin as soon as relatively stable problem behavior is detected in young children. Once professionals have identified young children who are at risk for stable externalizing behavior problems, it is important that they use and/or recommend research‐based interventions. Therefore, the first purpose of this article is to present research on specific child (e.g., temperament), family (e.g., family adversity), and transactional characteristics that have been documented to contribute to the manifestation of externalizing disorders in young children. School factors that may also support externalizing behavior in young children will also be presented and include negative teacher interactions and limited support for appropriate behavior. The second purpose of this manuscript is to present screening and intervention strategies that school psychologists could may use with young children who have externalizing behavior prior to or as soon as they enter the kindergarten setting. © 2002 Wiley Periodicals, Inc.
Exploring the relationship between school discipline referrals and delinquency
Authors: Sprague Jeffery , Walker Hill M. , Stieber Steve , Simonsen Brandi , Nishioka Vicki , Wagner Linda
Published: August 2002

There is a growing concern about violent and destructive behaviors of youth that require intervention by juvenile justice and youth‐serving agencies. This concern has led many to conclude that schools and community agencies must increase efforts to prevent juvenile delinquency and to provide programs that will facilitate rehabilitation, education, and vocational training for youth already involved. A clear understanding of the nature and range of behaviors that result in juvenile crime is needed in order to develop programs and interventions that can be expected to lead to beneficial changes for youth and for society as a whole. The purpose of this article is to describe the relationship between school behaviors and youth characteristics in school (e.g., discipline referrals, teacher nominations, nomothetic ratings) and referrals to juvenile authorities (e.g., illegal behaviors). We describe a strategy of using teacher nominations, school discipline referrals, and community arrest data to predict delinquent and violent behavior in youth. We outline data from a group of socially maladjusted middle school youth to illustrate the relationship between the two data sources and recommendations for identification and treatment of youth at risk for delinquency and antisocial behavior. © 2001 John Wiley & Sons, Inc.
Manganese‐based transition metal complexes as new catalysts for olefin polymerizations
Authors: Ban Hoang The , Kase Toshio , Murata Masahide
Published: August 2002

Three manganese complexes, Mn(acac)3 (acac = acetylacetonate), Cp2Mn (Cp = cyclopentadienyl), and Mn(salen)Cl [salen = 1,2‐cyclohexanediamino‐N,N′‐bis(3,5‐dit‐butyl‐salicylidene)], were used for ethylene and propylene polymerizations. These complexes, in combination with an alkylaluminum cocatalyst such as methylaluminoxane (MAO) or diethyl aluminum chloride (AlEt2Cl), could promote ethylene polymerizations that yielded extremely high molecular weight linear polymers, but were inactive for propylene polymerizations. The counterparts supported on MgCl2 showed activities even for propylene polymerizations and had remarkably enhanced activities for ethylene polymerizations. In the presence of an electron donor such as ethylbenzoate, the MgCl2‐supported manganese‐based catalysts yielded a highly isotactic polypropylene with a high molecular weight. © 2001 John Wiley & Sons, Inc. J Polym Sci Part A: Polym Chem 39: 3733–3738, 2001
Sulfobetaine zwitterionomers based on n‐butyl acrylate and 2‐ethoxyethyl acrylate: Monomer synthesis and copolymerization behavior
Authors: Gauthier Mario , Carrozzella Tony , Penlidis Alexander
Published: August 2002

New materials with potential applications for adhesives and coatings, based on copolymers containing zwitterionic pendent groups, were investigated. n‐Butyl acrylate and 2‐ethoxyethyl acrylate were copolymerized with a series of five zwitterionic sulfobetaine monomers. The structure of the monomers was varied in terms of the zwitterion intercharge spacing and the bulkiness of the alkyl substituents at the quaternary ammonium unit. Four of the five zwitterionic sulfobetaine methacrylate (SBM) monomers used in the study were synthesized. An evaluation of the reactivity ratios for the copolymer systems was performed with programs based on statistically sound techniques such as the error‐in‐variables model and the nonlinear‐least‐squares method. Reactivity ratio estimates for all 10 comonomer pairs were obtained, and they showed clear variations in reactivity with the structure of the SBM. In general, the more hydrophobic the SBM was, the lower its reactivity was with respect to the acrylate monomers. © 2002 John Wiley & Sons, Inc. J Polym Sci Part A: Polym Chem 40: 511–523, 2002; DOI 10.1002/pola.10138
Polymer‐supported reagents, catalysts, and sorbents: Evolution and exploitation—A personalized view
Authors: Sherrington D. C.
Published: August 2002

The solid‐phase method for oligopeptide synthesis was introduced by Professor Bruce Merrifield in 1963, but in practice the origins of polymer‐supported reagents, catalysts, and so forth trace back to the early development of ion exchange and catalysis by sulfonic acid resins. This highlight summarizes how the evolution of solid‐phase organic synthesis occurred in parallel with the development of supported reactive species and indicates the interchange between these areas in the last 30 years or so. The treatment is essentially a personalized one as seen from the author's own laboratory in the United Kingdom and is not intended to review the whole field. The emergence of the international series of conferences on polymer‐supported organic chemistry is emphasized as a key development that stimulated and maintained the area before its importance was recognized more widely by both academic and industrial chemists. The requirement of robotic technologies, as the basis for high‐throughput combinatorial and parallel synthesis in the pharmaceutical industry, has brought the relevance of supported chemistry to the attention of all synthetic chemists. At the same time, the recognition that all industrial chemical processes need to meet appropriate environmental standards has focused attention on the use of heterogenized reactive species as a potentially important technology for achieving the greening of chemistry. These two factors have brought polymer‐supported reactive chemistry to center stage, so to speak, and the early principles laid down over 2 decades ago are now being developed and exploited at an amazing rate. From a rather slow start, through a number of ups and downs in its development, the area of polymer‐supported chemistry now seems poised to join the more routine world of synthesis and to become a methodology used by all as and when appropriate. © 2001 John Wiley & Sons, Inc. J Polym Sci Part A: Polym Chem 39: 2364–2377, 2001
Various silicon‐containing polymers with Si(H)CC units
Authors: Itoh Masayoshi , Iwata Kenji , Ishikawa Jun‐Ichi , Sukawa Hiroshi , Kimura Hideaki , Okita Koichi
Published: August 2002

Nine new kinds of thermosetting polymers with the Si(H)CC unit were synthesized by dehydrogenative polycondensation reactions between hydrosilanes and diethynyl compounds in the presence of a magnesia catalyst. Phenylsilane, silane, vinylsilane, and n‐octylsilane were used as the hydrosilanes, and 1,3‐diethynylbenzene, 1,4‐diethynylbenzene, 4,4′‐diethynyldiphenyl ether, and 1,3‐diethynyl‐1,1,3,3‐tetramethyldisiloxane were used as the diethynyl compounds. All the polymers were thermosetting, highly heat‐resistant, easily soluble in a solvent, and moldable. In particular, Si(R)HCCC6H4CC (R = H or CHCH2) showed high thermal stability; the temperature of 5% weight loss was greater than 800 °C, and the residue at 1000 °C was over 90%. The thermal stabilities of the polymers were attributed to the crosslinking reaction of the SiH and CC bonds. © 2001 John Wiley & Sons, Inc. J Polym Sci Part A: Polym Chem 39: 2658–2669, 2001
Study of hydrogen‐bonding strength in poly(ϵ‐caprolactone) blends by DSC and FTIR
Authors: Kuo Shiao Wei , Huang Chih Feng , Chang Feng Chih
Published: August 2002

The hydrogen‐bonding strength of poly(ϵ‐caprolactone) (PCL) blends with three different well‐known hydrogen‐bonding donor polymers [i.e., phenolic, poly(vinyl‐phenol) (PVPh), and phenoxy] was investigated with differential scanning calorimetry and Fourier transform infrared spectroscopy. All blends exhibited a single glass‐transition temperature with differential scanning calorimetry, which is characteristic of a miscible system. The strength of interassociation depended on the hydrogen‐bonding donor group in the order phenolic/PCL > PVPh/PCL > phenoxy/PCL, which corresponds to the q value of the Kwei equation. In addition, the interaction energy density parameter calculated from the melting depression of PCL with the Nishi–Wang equation resulted in a similar trend in terms of the hydrogen‐bonding strength. Quantitative analyses on the fraction of hydrogen‐bonded carbonyl groups in the molten state were made with Fourier transform infrared spectroscopy for all systems, and good correlations between thermal behaviors and infrared results were observed. © 2001 John Wiley & Sons, Inc. J Polym Sci Part B: Polym Phys 39: 1348–1359, 2001
Modeling of particle‐dispersed melting mechanism and its application in corotating twin‐screw extrusion
Authors: Zhu Linjie , Narh K. A. , Geng Xiaozheng
Published: August 2002

Particle‐dispersed melting is a complex but important melting mechanism in the corotating twin‐screw extruder. In this study, the complex multi‐particle‐dispersed system was simplified into a single‐particle melting model. The finite‐difference method was introduced to solve this problem. The simulation results show that the melting of a particle may involve two steps: the heating stage and melting stage. The heating time and melting time depend on solid concentration, initial melt and solid temperature, and shear rate. Calculations indicate that high solid concentration and solid temperature, low melt temperature and shear rate will result in a more uniform temperature distribution after polymer melting. The model offers valuable information for designing the melting zone in a corotating twin‐screw extruder, especially at high screw speed. © 2001 John Wiley & Sons, Inc. J Polym Sci Part B: Polym Phys 39: 2461–2468, 2001
Communication between physicians and cancer patients about complementary and alternative medicine: exploring patients' perspectives
Authors: Tasaki Katsuya , Maskarinec Gertraud , Shumay Dianne M. , Tatsumura Yvonne , Kakai Hisako
Published: August 2002

The aim of this paper is to identify barriers to communication between physicians and cancer patients regarding complementary and alternative medicine (CAM) by exploring the perspectives of patients. In face of the recent popularity of CAM use among cancer patients, the lack of communication is a serious problem. A number of CAM therapies may interfere with conventional treatments and thus impact patients' well‐being and chances of survival. In addition, lack of communication is problematic in the health care context because the development of openness and trust between health care providers and clients is contingent upon effective interpersonal communication. We conducted semi‐structured interviews with 143 cancer patients to explore their experiences with CAM use. Using a qualitative research method, we examined interview data from 93 CAM users who provided sufficient information about communication issues. As a result, three themes emerged describing barriers to unsuccessful communication as perceived from the patient's point of view: physicians' indifference or opposition toward CAM use, physicians' emphasis on scientific evidence, and patients' anticipation of a negative response from their physician. Increasing education about CAM and regular assessment of CAM use may help physicians to be more aware of their patients' CAM use. As a result, physicians may provide patients with information on risks and benefits of CAM use and refer patients to other services that may address unmet needs. Given a difference in epistemiologic beliefs about cancer and its treatment, the challenge is to find a common ground for an open discussion in which physicians consider that scientific evidence is not all that counts in the life of an individual facing a serious disease. Copyright © 2002 John Wiley & Sons, Ltd.
Efficacy of sublingual immunotherapy in children with asthma and rhinitis: A double‐blind, placebo‐controlled study
Authors: Bahçeciler Nerin N. , Işik Uğur , Barlan Işil B. , Başaran Müjdat M.
Published: August 2002

To evaluate the efficacy of specific sublingual immunotherapy (SLIT), we enrolled 15 children with asthma and rhinitis (7 girls, 8 boys,mean ± SD age of 11.7 ± 3.3) allergic to house dust mite (HDM) into a double‐blind, placebo‐controlled study. After a run‐in period, patients were randomized to receive either placebo (n = 7) or SLIT (n = 8) with a standardized Dermatophagoides pteronyssinus (D. pteronyssinus) + Dermatophagoides farinea (D. farinea) 50/50 extract. They received increasing doses up to 100 index units of reactivity (IR) every day for 4 weeks, then 100 IR/day for another 4 weeks, followed by maintenance therapy consisting of 20 drops 2 times a week for 4 months. Efficacy was assessed at the end of 6 months of therapy according to symptom and medication scores, serum total IgE levels, results of lung function tests, methacholine provocation tests, and skin prick tests.

Daily means for the asthma score and use of inhaled beta‐2‐mimetics decreased significantly in the SLIT group (P = 0.05, P = 0.028, respectively), whereas no such difference was observed in the placebo group. At the end of follow‐up, mean daily doses of intranasal steroids needed for control of rhinitis symptoms decreased significantly in the SLIT group (P = 0.04). Baseline skin sensitivity to D. pteronyssinus and D. farinea was not significantly different between in the two groups, whereas end‐point wheal diameter obtained with D. pteronyssinus extract was significantly less in the SLIT vs. the placebo group (P = 0.026). At the end of 6 months, peak expiratory flow (PEF) values in the placebo group was significantly lower than in the SLIT group (P = 0.049). Throughout the treatment period, the SLIT group was found to have less asthma exacerbations than the placebo group (P = 0.007). The provocation concentration causing a 20% drop in forced expired volume in 1 sec did not change throughout the treatment period in either groups. None of the patients reported local or systemic side effects from SLIT.

Results of this study suggests that SLIT may be a useful alternative or additional therapy in the treatment of children with asthma/rhinitis due to HDM. Pediatr Pulmonol. 2001; 32:49–55. © 2001 Wiley‐Liss, Inc.
Impact of a pediatric asthma clinical pathway on hospital cost and length of stay*
Authors: Wazeka April , Valacer David J. , Cooper Mary , Caplan David W. , DiMaio Mary
Published: August 2002

This study sought to determine if a clinical pathway developed and executed by specialists in pediatric asthma would reduce hospital costs and length of stay (LOS). The study design was a retrospective, nonrandomized, controlled trial. Subjects were children aged 2–18 years (N = 1,004) with a history of recurrent wheezing, hospitalized with a diagnosis of acute asthma exacerbation between 1995–1998 at the New York Hospital‐Weill Cornell Medical Center and treated via the pathway, as well as a control group of 206 children ages 2–18 hospitalized for acute asthma exacerbation in 1994, the year prior to pathway implementation.

Patients were treated via the pathway under the supervision of an asthma specialist. The pathway provided guidelines for: 1) frequency of patient assessment; 2) bronchodilator usage; 3) corticosteroid use; 4) laboratory evaluation; 5) vital signs, oxygen saturation, and peak flow measurements; 6) chest x‐rays; 7) social work intervention; and 8) discharge planning. The main outcome measures were hospital length of stay, cost per hospitalization, nursing, medication, laboratory and radiology costs, and relapse rate. Total charges for admission and average LOS for 1995–1998 were calculated, and compared with 1994, the year preceding implementation of the pathway.

LOS decreased from 4.2 days to 2.7 days (P < 0.0001). The annual total charges for pediatric asthma admissions decreased from $2 million to $1.4 million (P < 0.005). Nursing and laboratory costs showed a statistically significant decrease. Follow‐up study at 8 months showed a readmission rate of 0.02%.

The implementation of a pediatric asthma clinical pathway, directed by specialists, resulted in significantly decreased length of stay and overall cost, without an increased rate of readmission. Pediatr Pulmonol. 2001; 32:211–216. © 2001 Wiley‐Liss, Inc.
Thermal unfolding molecular dynamics simulation of Escherichia coli dihydrofolate reductase: Thermal stability of protein domains and unfolding pathway
Authors: Sham Yuk Yin , Ma Buyong , Tsai Chung‐Jung , Nussinov Ruth
Published: August 2002

Temperature‐induced unfolding of Escherichia coli dihydrofolate reductase was carried out by using molecular dynamic simulations. The simulations show that the unfolding generally involves an initial end‐to‐end collapse of the adenine binding domain into partially extended loops, followed by a gradual breakdown of the remaining β‐sheet core structure. The core, which consists of β‐strands 5–7, was observed to be the most resistant to thermal unfolding. This region, which is made up of part of the N‐terminus domain and part of the large domain of the E. coli dihydrofolate reductase, may constitute the nucleation site for protein folding and may be important for the eventual formation of both domains. The unfolding of different domains at different stages of the unfolding process suggests that protein domains vary in stability and that the rate at which they unfold can affect the overall outcome of the unfolding pathway. This observation is compared with the recently proposed hierarchical folding model. Finally, the results of the simulation were found to be consistent with a previous experimental study (Frieden, Proc Natl Acad Sci USA 1990;87:4413–4416) which showed that the folding process of E. coli dihydrofolate reductase involves sequential formation of the substrate‐binding sites. Proteins 2002;46:308–320. © 2002 Wiley‐Liss, Inc.
Recurrence quantification analysis reveals interaction partners in paramyxoviridae envelope glycoproteins
Authors: Giuliani Alessandro , Tomasi Maurizio
Published: August 2002

The paramyxovirus envelope fuses with the host cell membrane by cooperative interaction of two transmembrane glycoproteins: the hemagglutinin neuraminidase (HN) and the fusion (F) glycoprotein. The interaction appears to be finely regulated, as both proteins must derive from the same viral species to obtain a functional interaction. Because HN and F do not form stable complexes, this interaction is poorly characterized. This article demonstrates that a modification of a classical bioinformatic method based on the co‐evolution of interacting partners can detect the specificity of the HN and F interaction. The proposed approach relies on a relatively new nonlinear signal analysis technique, recurrence quantification analysis (RQA), applied to the hydrophobicity sequences of viral proteins. This technique is able to shed light on the interaction between HN and F proteins in the virus–cell fusion and, more generally, permits the quantitative comparison of nonhomologue protein systems. On the contrary, the same co‐evolution approach, based on the classical sequence alignment procedure, was unable to discriminate interacting partners from the general strict correlation existing between the evolution of viral proteins as a whole. The cooperation between HN and F in the fusion process is thus demonstrated by a bioinformatic, purely sequence‐dependent, perspective. Proteins 2002;46:171–176. © 2001 Wiley‐Liss, Inc.
Multiple linear regression for protein secondary structure prediction
Authors: Pan Xian‐Ming
Published: August 2002

In the present work, a novel method was proposed for prediction of secondary structure. Over a database of 396 proteins (CB396) with a three‐state‐defining secondary structure, this method with jackknife procedure achieved an accuracy of 68.8% and SOV score of 71.4% using single sequence and an accuracy of 73.7% and SOV score of 77.3% using multiple sequence alignments. Combination of this method with DSC, PHD, PREDATOR, and NNSSP gives Q3 = 76.2% and SOV = 79.8%. Proteins 2001;43:256–259. © 2001 Wiley‐Liss, Inc.
Generalized comparative modeling (GENECOMP): A combination of sequence comparison, threading, and lattice modeling for protein structure prediction and refinement
Authors: Kolinski A. , Betancourt M.R. , Kihara D. , Rotkiewicz P. , Skolnick J.
Published: August 2002

An improved generalized comparative modeling method, GENECOMP, for the refinement of threading models is developed and validated on the Fischer database of 68 probe–template pairs, a standard benchmark used to evaluate threading approaches. The basic idea is to perform ab initio folding using a lattice protein model, SICHO, near the template provided by the new threading algorithm PROSPECTOR. PROSPECTOR also provides predicted contacts and secondary structure for the template‐aligned regions, and possibly for the unaligned regions by garnering additional information from other top‐scoring threaded structures. Since the lowest‐energy structure generated by the simulations is not necessarily the best structure, we employed two structure‐selection protocols: distance geometry and clustering. In general, clustering is found to generate somewhat better quality structures in 38 of 68 cases. When applied to the Fischer database, the protocol does no harm and in a significant number of cases improves upon the initial threading model, sometimes dramatically. The procedure is readily automated and can be implemented on a genomic scale. Proteins 2001;44:133–149. © 2001 Wiley‐Liss, Inc.
Chlorothalonil and chlorpyrifos degradation products in golf course leachate
Authors: Armbrust Kevin L
Published: August 2002

Chlorothalonil and chlorpyrifos are commonly used to control disease and insect pests on golf course greens. While they are relatively immobile in the soil profile, their respective soil degradation products, 4‐hydroxy‐2,5,6‐trichloroisophthalonitrile and 3,5,6‐trichloropyridin‐2‐ol are more polar and may be present in golf course green leachate. To investigate this possibility, six stainless steel lysimeters were constructed into two practice greens at a country club in a northern Atlanta, Georgia suburb. Over a period of 1 year after rainfall events, lysimeter leachate samples were collected into glass bottles, filtered and directly analyzed by HPLC with UV detection. Chlorpyrifos was not detected in any sample and chlorothalonil was detected only in one sample, at a concentration of 0.12 mg liter−1. With a limit of quantitation of 0.05 mg liter−1, hydroxychlorothalonil and trichloropyridinol were detected in 87% and 63% of the samples at maximum and median concentrations of 2.21 and 0.55 mg liter−1 for hydroxychlorothalonil and 1.77 and 0.15 mg liter−1 for trichloropyridinol. Golf course green leachate often mixes with surface water, thus more data may be warranted to determine the persistence and ecological significance of chronic exposure to these compounds of organisms in the aquatic environment.

© 2001 Society of Chemical Industry
Dye injection for predicting pesticide movement in micro‐irrigated polyethylene film mulch beds
Authors: Csinos Alex S , Laska James E , Childers Stan
Published: August 2002

A new method is described for tracing water movement in polyethylene film covered soil beds. Dye was delivered via a drip tape micro‐irrigation system which was placed in the bed as the soil beds were shaped and covered with polyethylene film. The dye was injected into the system and irrigated with water for 4–24 h at 0.41–1.38 bar (41–138 kPa) pressure depending on the experiment. The dye appeared as blue circles on the soil surface within 20 min of injection and produced a three‐dimensional pattern in the soil profile. Injection‐irrigation‐pressure scenarios were evaluated by measuring dye movement directly below and between emitters by sliding fabricated blades vertically into the bed at the desired examination point and excavating the soil away from the blade. The dye typically produced a U shape on the face of the bed and the area was calculated for each of these exposed faces. The area increased as the length of irrigation and water pressure increased. Interrupted irrigation (pulsing) scenarios did not alter the calculated areas encompassed by the dye compared to uninterrupted irrigation scenarios. The blue dye provided a direct, inexpensive and easy method of visualizing water movement in soil beds. This information will be used to optimize application of emulsifiable plant‐care products in polyethylene film mulch beds.

© 2002 Society of Chemical Industry
A review of potential pathogens of sea lice and the application of cleaner fish in biological control
Authors: Treasurer James W
Published: August 2002

There are many examples of successful biological control of pest populations in aquatic environments. This approach to sea louse control has environmental benefits and is cost‐effective. The range of possible pathogens of lice is reviewed and epibionts recorded from sea lice, including the monogenean Udonella caligorum and ciliates, are examined. Baculoviruses when ingested by insects form occlusion bodies resulting in severe damage to the digestive system and subsequent death, and this may be a promising approach. Cleaner wrasse (Labridae) have been stocked commercially with farmed salmon since 1989, and recent work on improving the method is reviewed. Wrasse are sourced from a wild fishery and stocked at ratios of 1 to 25–150 salmon. Over 5 million wrasse are stocked annually in Norway and c 30% of smolts in Scotland were stocked with wrasse until 1998, when an outbreak of infections salmon anaemia (ISA) deterred many farmers from transferring wild fish to cages. A case study is given showing that salmon in cages stocked with wrasse had a burden of one to eight lice through the first year compared with up to 40 lice per fish on unprotected and untreated fish. Electivity indices were used to compare the relative composition of lice developmental stages on salmon in stocked and unstocked cages, and adult male and female lice were found to comprise only 6% of the population in cages with wrasse, compared with 49% adults on fish in control cages. Measures to improve the efficacy of wrasse as a way of cleaning salmon in the second production year include the use of refuges to assist over‐wintering survival, and stocking ballan wrasse. Health hygiene includes sourcing wrasse in the farm locality, testing for pathogens, vaccination of wrasse and ultimately rearing wrasse for stocking. The role of wrasse in an IPM strategy is described.

© 2002 Society of Chemical Industry
Chemistry and pharmacology of the citrus bioflavonoid hesperidin
Authors: Garg A. , Garg S. , Zaneveld L. J. D. , Singla A. K.
Published: August 2002

Hesperidin, a bioflavonoid, is an abundant and inexpensive by‐product of Citrus cultivation. A deficiency of this substance in the diet has been linked with abnormal capillary leakiness as well as pain in the extremities causing aches, weakness and night leg cramps. No signs of toxicity have been observed with the normal intake of hesperidin or related compounds.

Both hesperidin and its aglycone hesperetin have been reported to possess a wide range of pharmacological properties. This paper reviews various aspects of hesperidin and its related compounds, including their occurrence, physical and chemical properties, analysis, pharmacokinetics, safety and toxicity and the marketed products available. A special emphasis has been laid on the pharmacological properties and medicinal uses of these compounds. Copyright © 2001 John Wiley & Sons, Ltd.
In vitro cytotoxicity of flavonoids against MK2 and C6 tumour cells
Authors: Sánchez I. , Calderón J. , Ruiz B. , Tellez J. , Calzada L. , Taboada J.
Published: August 2002

The cytotoxic effect of five flavonoids isolated from the aerial parts of the Asteraceae family of plants were studied in vitro using LLC‐MK2 and C6 glial cells. Agehoustin A was shown to be cytotoxic for both cells (71% or 67% cell death). Agehoustin B and artemetin, which lack a methoxy group at C‐8 (RI), were not cytotoxic for the cells (19% and 16% cell death). The three flavonoids showed considerable suppressive effects on LLC‐MK2 and C6 cell growth. Lucidin‐dimethylether and gnaphaliin were also not cytotoxic for cells but they had no suppressive effect on cell growth. The results show a structure–cytostatic activity relationship. We suggest that the methoxy group on C‐8 and on the B ring are responsible for death cell. Copyright © 2001 John Wiley & Sons, Ltd.
Simple evaluation of Franck–Condon factors and non‐Condon effects in the Morse potential
Authors: López V. J. C. , Rivera A. L. , Smirnov Yu. F. , Frank A.
Published: August 2002

The calculation of Franck–Condon factors between different 1‐D Morse potential eigenstates using a formula derived from the Wigner function is discussed. Our numerical calculations using a simple program written in Mathematica are compared with other calculations. We show that our results have a similar accuracy as those calculations performed with more sophisticated methods. We discuss the extension of our method to include non‐Condon effects in the calculation. © 2002 Wiley Periodicals, Inc. Int J Quantum Chem 88: 280–295, 2002
B3LYP studies of the formation of neutral tyrosyl radical Yz⋅ and regeneration of neutral tyrosine Yz in PSII
Authors: Wang Yan‐Ni , Eriksson Leif A.
Published: August 2002

Tyrosine Y161 (Yz) plays an important role in the charge separation of photosystem II (PSII) by reducing photooxidized P680+ and thus forming a neutral tyrosyl radical. The neutral tyrosyl radical then abstracts an electron and a proton from the manganese cluster (or other proton source) to regenerate neutral tyrosine. The production of the neutral tyrosyl radical is closely related to the oxidation of tyrosine by P680+ and deprotonation by a neighbouring histidine. The regeneration of neutral tyrosine is more complicated, involving the manganese cluster and other protein bases. Hybrid density functional calculations (B3LYP) show that the electron transfer between tyrosine and P680+ is coupled to the proton transfer between tyrosine and histidine. The proton is transferred from tyrosine to histidine spontaneously as tyrosine is oxidized, forming Yz⋅‐ ‐H+His state. The theoretical results of the formation of the neutral tyrosyl radical agrees with recent experimental and previous computational results. Neutral tyrosine is difficult to regenerate directly via abstraction of a hydrogen atom from water. The possible proton transfer from histidine cation directly to water or with glutamic acid assitance are both endothermic. In both cases, the proton lies between tyrosine and histidine and shifts back to tyrosine spontaneously when the tyrosyl radical is reduced. This result is consistent with Junge's electron transfer model. However, when glutamate anion is present, rather than glutamic acid, the proton transfers spontaneously via histidine to glutamate as tyrosine is oxidized, forming Yz⋅‐ ‐His‐ ‐Glu state. © 2001 John Wiley & Sons, Inc. Int J Quant Chem 83: 220–229, 2001
Reduced density matrices—Then and now*
Authors: Coleman A. John
Published: August 2002

The history and results of over forty years of research on the theory of reduced density matrices is discussed, and several key unsolved research problems announced. © 2001 John Wiley & Sons, Inc. Int J Quantum Chem, 2001
Role of electron–electron coalescence density in density functional theory
Authors: Valderrama E. , Ugalde J. M.
Published: August 2002

An expression for the evaluation of electron–electron coalescence density as a functional of the density for any electron system is proposed. The formula, clarifies previously advanced upper bounds for this quantity and provides a method to independently estimate the system‐averaged on‐top exchange–correlation hole. The relationship with the on‐top pair density shows that producing the true electron–electron coalescense should be considered as a leading physical requirement for trial wave functions in any energy minimization scheme. © 2002 John Wiley & Sons, Inc. Int J Quantum Chem, 2001
Evaluation of mass discrimination effects in the quantitative analysis of polydisperse polymers by matrix‐assisted laser desorption/ionization time‐of‐flight mass spectrometry using uniform oligostyrenes
Authors: Shimada Kayori , Lusenkova Marina A. , Sato Keisuke , Saito Takeshi , Matsuyama Shigetomo , Nakahara Hisae , Kinugasa Shinichi
Published: August 2002

Mass discrimination effects in matrix‐assisted laser desorption/ionization time‐of‐flight mass spectrometry (MALDI‐TOFMS) were quantitatively investigated using equiweight and equimolar mixtures of uniform polystyrene (PS) oligomers. Uniform PS oligomers were separated by preparative super‐critical fluid chromatography (SFC) from commercial standard PS samples. The separated PS oligomers, with degrees of polymerization n = 2–25, have absolutely no molecular weight distributions. Equiweight and equimolar mixtures of uniform PS oligomers were accurately prepared by weighing by microbalance, and their spectra were recorded using a MALDI‐TOF mass spectrometer. In the lower molecular weight region (less than about 103) the oligomers with lower molecular weights give lower mass spectral intensities, with no correlation with laser power. In contrast, higher laser powers yield a decrease of mass spectral intensities in the higher molecular weight region. These results clearly show that mass discrimination effects occur at lower and higher molecular weights depending on the laser power, and provide quantitative information about the discrimination. Using the data on equiweight and equimolar mixtures of PS oligomers, it was possible to calibrate the MALDI‐TOF mass spectral data for an analysis of molecular weight distribution of a standard monodisperse PS sample with number‐averaged molecular weight of 103, and to compare it with the molecular weight distribution measured by analytical SFC. The result from the calibrated MALDI‐TOF mass spectrum, however, does not agree perfectly with that from the SFC results, because undetectable peaks in MALDI‐TOF mass spectra at lower and higher molecular weights could not be included in the calibration of peak intensities. Copyright © 2001 John Wiley & Sons, Ltd.
High‐throughput semi‐automated 96‐well liquid/liquid extraction and liquid chromatography/mass spectrometric analysis of everolimus (RAD 001) and cyclosporin a (CsA) in whole blood
Authors: Brignol Nastry , McMahon Louis M. , Luo Suyi , Tse Francis L. S.
Published: August 2002

A semi‐automated high‐throughput liquid/liquid extraction (LLE) assay was developed for RAD001 and cyclosporin A (CsA) in human blood. After addition of internal standard and ammonium hydroxide, samples were extracted twice with methyl tert‐butyl ether (MTBE). The organic extract was evaporated to dryness and reconstituted in mobile phase. Where possible, sample transfer and LLE steps were automated using a Tomtec Quadra 96 workstation. Samples were analyzed using ESI‐LC/MS/MS employing the transitions of ([M + NH4]+ → [M + H]+) for CsA and ([M + NH4]+ → [M + H‐(CH3OH + H2O)]+) for RAD001, under isocratic chromatographic conditions (75:25, (v/v), acetonitrile/20 mM ammonium acetate) with a run time of 3.6 min. A lower limit of quantitation (LLOQ) of 0.368 ng/mL and 5.23 ng/mL was achieved for RAD001 and CsA, respectively, using a sample volume of 0.3 mL for the analysis. The method was validated over a 3‐day period and the resulting calibration curves had a correlation coefficient >0.99 over the concentration range 0.368 to 409 ng/mL and 5.24 to 1748 ng/mL for RAD001 and CsA, respectively. The inter‐day coefficient of variation (CV) was less than 15% at the LLOQ for both compounds. The method was applied to the analysis of clinical samples. Under normal working conditions four 96‐well plates could be extracted and LC/MS analysis completed in less than 28 h. A marked improvement in sample throughput efficiency was realized with this LLE method when compared to existing solid phase extraction (SPE) methods which deal with both RAD001 and CsA. Copyright © 2001 John Wiley & Sons, Ltd.
Consequence of boar edible tissue consumption on urinary profiles of nandrolone metabolites. II. Identification and quantification of 19‐norsteroids responsible for 19‐norandrosterone and 19‐noretiocholanolone excretion in human urine
Authors: De Wasch Katia , Bizec Bruno Le , Brabander Hubert De , André François , Impens Sandra
Published: August 2002

In previous work (Le Bizec et al., Rapid Commun. Mass Spectrom. 2000; 14: 1058), it was demonstrated that a boar meal intake could lead to possible false accusations of abuse of 17β‐nortestosterone in antidoping control. The aim of the present study was to identify and quantify endogenous 19‐norsteroids in boar edible tissue at concentrations that can alter the steroid urinary profile in humans, and lead to excretion of 19‐norandrosterone (19‐NA) and 19‐noretiocholanolone (19‐NE). The samples were analysed in two laboratories. The methodologies used for extraction and detection (GC/MS(EI) and LC/MS/MS(APCI+)) are compared and discussed. 19‐Norandrostenedione (NAED), 17β‐ and 17α‐nortestosterone (bNT, aNT), and 17β‐ and 17α‐testosterone (bT, aT) were quantified. The largest concentrations of NAED and bNT were observed in testicles (83 and 172 µg/kg), liver (17 and 63 µg/kg) and kidney (45 and 38 µg/kg). A correlation between the bNT and NAED content of a typical meal prepared with boar parts and the excreted concentrations of 19‐NA and 19‐NE in human urine was demonstrated. Copyright © 2001 John Wiley & Sons, Ltd.