bluuebunny/crossref_metadata_2025 huggingface dataset:
Finite element approximations with quadrature for second‐order hyperbolic equations
Authors: Sinha Rajen Kumar
Published: October 2002

In this article, the effect of numerical quadrature on the finite element Galerkin approximations to the solution of hyperbolic equations has been studied. Both semidiscrete and fully discrete schemes are analyzed and optimal estimates are derived in the L∞(H1), L∞(L2) norms, whereas quasi‐optimal estimate is derived in the L∞(L∞) norm using energy methods. The analysis in the present paper improves upon the earlier results of Baker and Dougalis [SIAM J Numer Anal 13 (1976), pp 577–598] under the minimum smoothness assumptions of Rauch [SIAM J Numer Anal 22 (1985), pp 245–249] for a purely second‐order hyperbolic equation with quadrature. © 2002 Wiley Periodicals, Inc. Numer Methods Partial Differential Eq 18: 537–559, 2002; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/num.10022
Synthesis and NMR characterization of 6‐Phenyl‐6‐deoxy‐2,3‐di‐O‐methylcellulose
Authors: (Nozar) D. Sachinvala Navzer , Winsor David L. , Hamed Othman , Niemczura Walter P. , Maskos Karol , Vigo Tyrone L. , Bertoniere Noelie R.
Published: October 2002

Cellulose (1) was converted for the first time to 6‐phenyl‐6‐deoxy‐2,3‐di‐O‐methylcellulose (6) in 33% overall yield. Intermediates in the five‐step conversion of 1 to­6 were: 6‐O‐tritylcellulose (2), 6‐O‐trityl‐2,3‐di‐O‐methylcellulose (3), 2,3‐di‐O‐methylcellulose (4); and 6‐bromo‐6‐deoxy‐2,3‐di‐O‐methylcellulose (5). Elemental and quantitative carbon‐13 analyses were concurrently used to verify and confirm the degrees of substitution in each new polymer. Gel permeation chromotography (GPC) data were generated to monitor the changes in molecular weight (DPw) as the synthesis progressed, and the compound average decrease in cellulose DPw was ∼ 27%. Differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA) were used to characterize the decomposition of all polymers. The degradation temperatures ( °C) and percent char at 500 °C of cellulose derivatives 2 to 6 were 308.6 and 6.3%, 227.6 °C and 9.7%, 273.9 °C and 30.2%, 200.4 °C and 25.6%, and 207.2 °C and 27.0%, respectively. The glass transition temperature (Tg) of­6‐O‐tritylcellulose by dynamic mechanical analysis (DMA) occurred at 126.7 °C and the modulus (E′, Pa) dropped 8.9 fold in the transition from −150 °C to + 180 °C (6.6 × 109 to 7.4 × 108 Pa). Modulus at 20 °C was 3.26 × 109 Pa. Complete proton and carbon‐13 chemical shift assignments of the repeating unit of the title polymer were made by a combination of the HMQC and COSY NMR methods. Ultimate non‐destructive proof of carbon–carbon bond formation at C6 of the anhydroglucose moiety was established by generating correlations between resonances of CH26 (anhydroglucose) and C1′, H2′, and H6′ of the attached aryl ring using the heteronuclear multiple‐bond correlation (HMBC) method. In this study, we achieved three major objectives: (a) new methodologies for the chemical modification of cellulose were developed; (b) new cellulose derivatives were designed, prepared and characterized; (c) unequivocal structural proof for carbon–carbon bond formation with cellulose was derived non‐destructively by use of one‐ and two‐dimensional NMR methods. Copyright © 2002 John Wiley & Sons, Ltd.
The role of tumour‐associated macrophages in tumour progression: implications for new anticancer therapies
Authors: Bingle L. , Brown N. J. , Lewis C. E.
Published: October 2002

The role of macrophages in tumour growth and development is complex and multifaceted. Whilst there is limited evidence that tumour‐associated macrophages (TAMs) can be directly tumouricidal and stimulate the anti‐tumour activity of T cells, there is now contrasting evidence that tumour cells are able to block or evade the activity of TAMs at the tumour site. In some cases, tumour‐derived molecules even redirect TAM activities to promote tumour survival and growth. Indeed, evidence has emerged for a symbiotic relationship between tumour cells and TAMs, in which tumour cells attract TAMs and sustain their survival, with TAMs then responding to micro‐environmental factors in tumours such as hypoxia (low oxygen tension) by producing important mitogens as well as various growth factors and enzymes that stimulate tumour angiogenesis. This review presents evidence for the number and/or distribution of TAMs being linked to prognosis in different types of human malignancy. It also outlines the range of pro‐ and anti‐tumour functions performed by TAMs, and the novel therapies recently devised using TAMs to stimulate host immune responses or deliver therapeutic gene constructs to solid tumours. Copyright © 2002 John Wiley & Sons, Ltd.
‘Senescence‐associated’ β‐galactosidase activity in the upper gastrointestinal tract
Authors: Going James J. , Stuart Robert C. , Downie Martin , Fletcher‐Monaghan Aileen J. , Nicol Keith W.
Published: October 2002

β‐galactosidase activity at pH 6 is associated in vitro with senescence and cellular death, but in vivo data are sparse. This study undertook firstly to map ‘senescence‐associated’ β‐galactosidase activity (SAβG) at pH 6 in normal epithelia and mucosae of the upper gastrointestinal tract. As escape from senescence confers a proliferative advantage, a reduction in SAβG activity might be predicted in neoplasia and their precursors in vivo. This prediction was tested in metaplastic, dysplastic, and neoplastic epithelium of the upper gastrointestinal tract. Histochemical staining for SAβG was performed at pH 6 on cryostat sections of 350 endoscopic biopsies from sites including oesophagus, stomach, and duodenum of 46 patients: 28 with Barrett's oesophagus (two with adenocarcinoma), 15 with gastric adenocarcinoma, and three with oesophageal squamous cancer. A staining score (range 0–6) was assigned to epithelial cells in all mucosae and scores were calculated for surface (luminal), intermediate, and deep (basal) layers. The strongest SAβG activity was in surface luminal cells of normal duodenal mucosa (mean score 3.6±0.5; n=19), ‘specialized’ Barrett's mucosa (mean 2.2±0.12; n=105), and intestinal metaplasia in the stomach (mean 2.4±0.40; n=16). Squamous epithelium was consistently negative for SAβG activity. Low‐ and high‐grade Barrett's dysplasia showed no decrease in SAβG activity, but reduced activity was seen in gastric and oesophageal adenocarcinomas (mean 1.24±0.29; n=17; p=0.012). In six gastric adenocarcinomas, there was no detectable activity. Whether SAβG is truly a marker of cellular senescence in vivo remains to be determined. Activity is low in mucosal proliferation compartments and increases with cellular differentiation, especially in native or metaplastic intestinal mucosae. SAβG activity persists in dysplastic mucosae but may show some reduction or loss in adenocarcinomas (p=0.0012). Loss of SAβG activity is not, therefore, an early event in glandular dysplasia–neoplasia of the upper gastrointestinal tract. Copyright © 2002 John Wiley & Sons, Ltd.
Gene expression of TrkC (NTRK3) in human soft tissue tumours
Authors: Hisaoka Masanori , Sheng Wei‐Qi , Tanaka Atsuko , Hashimoto Hiroshi
Published: October 2002

TrkC is a member of the Trk family of tyrosine kinase receptors and plays an important role in the development and maintenance of neural tissues. Although a variety of non‐neuronal tissues have also been shown to express TrkC, the status of TrkC in soft tissue tumours has been poorly investigated, except for a small fraction of tumours including congenital/infantile fibrosarcoma characterized by an ETV6–NTRK3 (also known as Tel–TrkC) fusion gene. To broaden knowledge about the TrkC status in human neoplasms, the expression of TrkC transcripts was assessed in 51 soft tissue tumours of variable lines of differentiation by reverse transcription‐polymerase chain reaction (RT‐PCR), using primer sets flanking their extracellular domain, the tyrosine kinase domain, and the intracellular domain of a truncated variant (Trunc 1) described previously. In 44 of the 51 tumours, TrkC transcripts, including alternatively spliced isoforms, were detected. The truncated transcripts (Trunc 1) were co‐expressed in 40 of the 44 tumours and were expressed in one tumour without native TrkC gene expression. In two of the remaining six tumours, part of the sequence coding the tyrosine kinase domain of TrkC appeared to be truncated. Using a 3′ rapid amplification of cDNA ends (3′RACE) method, another truncated isoform (Trunc 2) was isolated from one of the tumours, in which the TrkC transcript was terminated with a novel 160‐base pair sequence. This truncated isoform was identified in nine of the 51 tumours examined by RT‐PCR using primers for Trunc 2. There was no clear correlation between the types of TrkC isoforms detected and histological types or grades of the tumours. These results suggest that human soft tissue tumours widely express TrkC, irrespective of their cellular lineage, morphology, and biological behaviour. Dysregulated TrkC expression may enhance overgrowth or transformation of various mesenchymal cells. Copyright © 2002 John Wiley & Sons, Ltd.
Maternal serum hyperglycosylated human chorionic gonadotrophin (HhCG) in the first trimester of pregnancies affected by Down syndrome, using a sialic acid‐specific lectin immunoassay
Authors: Spencer K. , Talbot J. A. , Abushoufa R. A.
Published: October 2002

In a series of 54 cases of pregnancies complicated by Down syndrome and 224 unaffected pregnancies we examined maternal serum levels of hyperglycosylated human chorionic gonadotrophin (HhCG) in samples collected in the first trimester (11–13 weeks) using a sialic acid‐specific lectin immunoassay. We compared these levels with those of other potential first trimester serum markers [free β‐hCG, pregnancy‐associated plasma protein A (PAPP‐A) and total hCG (ThCG)] and modeled detection rates and false‐positive rates of various biochemical markers in conjunction with fetal nuchal translucency (NT) and maternal age using an maternal age standardized population. Maternal serum HhCG in cases of Down syndrome were significantly elevated (median MoM 1.97) with 24/54 (44%) of cases above the 95th centile for unaffected pregnancies. Free β‐hCG was also elevated (median MoM 2.09) with 33% of cases above the 95th centile. PAPP‐A levels were reduced (median MoM 0.47) with 38% below the 5th centile. ThCG levels, whilst elevated (median MoM 1.34), had only 20% of cases above the 95th centile. Maternal serum HhCG levels were not correlated with fetal NT but showed significant correlation with ThCG and free β‐hCG and with PAPP‐A in the Down syndrome group (r=0.536). Maternal serum HhCG levels in cases with Down syndrome had a significant correlation with gestational age, increasing as the gestation increased. When HhCG was combined together with fetal NT, PAPP‐A and maternal age, at a 5% false‐positive rate the modeled detection rate was 83%, some 6% lower than when free β‐hCG was used and some 4% better than when ThCG was used. Maternal serum HhCG is unlikely to be of additional value when screening for Down syndrome in the first trimester. Copyright © 2002 John Wiley & Sons, Ltd.
Prenatal diagnosis of a 45,X male with a SRY‐bearing chromosome 21
Authors: Nataf V. , Senat M. V. , Albert M. , Bidat L. , Mazancourt P. de , Roume J. , Allard L. , Tessier D. Le , Ville Y. , Selva J.
Published: October 2002

Male phenotype associated with a 45,X karyotype is an infrequent finding. We present a case diagnosed prenatally on amniocentesis performed for maternal age. The male phenotype was associated with a translocation of a distal part of Yp including the pseudoautosomal SHOX gene and SRY gene on the short arm of a chromosome 21. By DNA analysis we could show that the X chromosome was of maternal origin and that the breakpoint was in interval 3 of the Y chromosome. Mechanisms and genetic counselling are discussed based on a review of published cases of 45,X and XX males. Copyright © 2002 John Wiley & Sons, Ltd.
Isochromosome 5p mosaicism at prenatal diagnosis: observations and outcomes in six cases at chorionic villus sampling and one at amniocentesis
Authors: Wilson Susan Clement , Susman Marleen , Bain Sharon , Wohlferd Monica , Dyke Daniel L. Van , Daniel Art , White Beverly , Gardner R. J. McKinlay
Published: October 2002

We present six cases of 47,+i(5p)/46 mosaicism diagnosed at chorionic villus sampling (CVS), this being the first prospective series to be reported. The clinical indication in each was advanced maternal age. Further prenatal studies in four (amniocentesis, plus fetal blood sampling in one) did not show the isochromosome. In one case, subsequent amniocentesis showed 1/48 in situ colonies with the isochromosome, but fetal blood was karyotypically normal. These five pregnancies resulted in phenotypically normal livebirths; further normal follow‐up reports (from age 4 months through 4 years) are noted in four of these. Analysis of placental tissue in one case confirmed the presence of the i(5p) mosaicism. In the remaining case, in which 100% of CVS cultured cells had the i(5p), the pregnancy was terminated. Fetal skin fibroblasts did not show the i(5p). Thus, in none of these six cases was true fetal mosaicism detected, nor an abnormal phenotype noted. We suggest that a 47,+i(5p)/46 karyotype, detected at CVS, may frequently reflect confined placental mosaicism. In addition, we report a case of the primary diagnosis of 47,+i(5p)/46 mosaicism at amniocentesis. The infant appeared normal at birth, but a brain malformation was subsequently identified. Copyright © 2002 John Wiley & Sons, Ltd.
Obesity treatment — benefits and risks with special reference to type 2 diabetes mellitus
Authors: Lawrence Victor , Coppack Simon
Published: October 2002

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Obesity and its complications pose one of the most important challenges to 21st century health care. Although its exponential rise in prevalence undoubtedly represents a major threat to the health of the population, treatment must be tailored to the individual concerned. Exclusive reliance on body mass index (BMI) alone to define management goals is not sufficient. Treatment planning must take into account the possibility that physical and psychological harm may result from repeated failure to achieve or maintain weight loss.

Therefore, specific and holistic indices of individual risk are required so that achievable and appropriate goals may be set in individual circumstances. Such goals may range from simple weight maintenance with risk factor modification, to moderate (5–10%) weight loss with or without drug therapy and, in carefully selected cases, to massive weight loss usually with bariatric surgery. This article will review the benefits and risks of weight loss in different individual circumstances, particularly type 2 diabetes, and critically examine the existing population studies, many of which superficially appear to suggest that weight loss is associated with increased rather than decreased overall mortality. Copyright © 2002 John Wiley & Sons, Ltd.
Reports of withdrawal syndrome with the use of SSRIs: a case/non‐case study in the French Pharmacovigilance database
Authors: Trenque T. , Piednoir D. , Frances C. , Millart H. , Germain M. L.
Published: October 2002

The SSRIs can be associated with withdrawal reactions and the objective of this study is to test the existence of an association between reports of withdrawal syndromes with the selective serotonin re‐uptake inhibitors in the French spontaneous reports database. All reactions are coded according to the WHO ART dictionary. Cases are reports of reactions of interest (withdrawal syndrome). Non‐cases are all reports of reactions other than those being studied. We calculated the odds ratio (OR) as the ratio of the odds of the association of reports of withdrawal syndrome with SSRIs in cases and non‐cases. SSRIs are clearly associated with a higher risk of withdrawal syndrome (OR: 5.05, 95% CI: 3.81–6.68) and in particular with venlafaxine and paroxetine (OR: 12.16, 95% CI: 6.17–23.35 and OR: 8.47, 95% CI: 5.63–12.65, respectively). The risk of withdrawal reactions appears to be greater with short half‐life drugs such as paroxetine and venlafaxine. The precise mechanisms have not been identified. Copyright © 2002 John Wiley & Sons, Ltd.
Correlations and topology of triangular benzenoid hydrocarbons: a comparative study of two series representing the least and most stable benzenoid hydrocarbons
Authors: Dias Jerry Ray
Published: October 2002

While reviewing aspects of our topological paradigm and the benchmark role played by the benzenoid polyradicals shaped like equilateral triangles, the topological properties of the reactive polyradicals and their stable associated leapfrog total‐resonant‐sextet benzenoids are studied. Copyright © 2001 John Wiley & Sons, Ltd.
Ring‐opening reactions of 5‐(aryl)thianthrenium bromides with aryl thiolates
Authors: Qian Ding‐Quan , Liu Bo , Shine Henry J. , Guzman‐Jimenez Ilse Y. , Whitmire Kenton H.
Published: October 2002

A series of 5‐(aryl)thianthrenium bromides (6a–e) with aryl (Ar) groups phenyl (a), p‐tolyl (b), p‐anisyl (c), p‐chlorophenyl (d) and p‐bromophenyl (e) was prepared by reaction of thianthrene 5‐oxide with the appropriate Grignard reagent ArMgBr. Reactions of 6a–e with aryl thiolates (Ar′SNa, Ar′ = phenyl, p‐tolyl and p‐chlorophenyl, 7a–c) were carried out in MeCN at room temperature. Products from 6a–c were a small amount of arene [benzene (8a) and toluene (8b)], and substantial amounts of ArSAr′ (9), thianthrene (Th) and a trisulfide, namely a 2‐(ArS)‐2′‐(Ar′S)‐diphenyl sulfide (10). Products from reactions of 6d,e were smaller amounts of 9 and 10 but substantial amounts of 1,4‐di(Ar′S)benzene (11) and a tetrasulfide (12a–c). The reactions that lead to products 9–12 are attributed to ligand coupling (LC) pathways in sulfuranes formed by attack of Ar′S− at the sulfonium S atom of 6. In the formation of 11 and 12 the halogen atom (Cl, Br) is first displaced from 6d,e by Ar′S−, giving a new thianthrenium ion (14) from which sulfurane formation (15) follows. Products 10 and 12 result from opening of the thianthrenium ring of sulfuranes 13 and 15 through LC. Products were assayed with a combination of GC and isolation with TLC, and were identified with a combination of GC (authentic compounds), x‐ray crystallography (10a), elemental analyses and high‐resolution mass spectrometry. The reactions of 6 are compared with earlier reactions of 5‐(alkoxy)‐and 5‐(alkyl)thianthrenium salts (1 and 2). Copyright © 2002 John Wiley & Sons, Ltd.
Kinetics of reduction of chloramines by sodium borohydride
Authors: Duriche Cécile , Darwich Chaza , Elkhatib Mazen , Tabcheh Mohamad , Delalu Henri
Published: October 2002

The reduction of chloramine, methylchloramine, dimethylchloramine and N‐chloro‐3‐azabicyclo­[3.3.0]octane by sodium borohydride was studied according to pH, temperature and concentrations of haloamine and reducing agent. The interaction is bimolecular and exhibits a specific acid catalysis. The enthalpy and entropy of activation were determined at pH 12.89. A mathematical treatment of the reaction kinetics allows the complete characterization of the final state and determination of the percentage of reduced haloamine in terms of [NaBH4]/[R1R2NCl] ratio, pH and temperature. A reaction mechanism is proposed. Copyright © 2002 John Wiley & Sons, Ltd.
Synthesis and characterization of water‐soluble hyperbranched poly(ester amine)s from diacrylates and diamines
Authors: Gao Chao , Tang Wei , Yan Deyue
Published: October 2002

Various water‐soluble hyperbranched poly(ester amine)s were synthesized by the direct polyaddition of diamines to diacrylates in the absence of a catalyst. Each diamine contained a secondary amino group and a primary amino group such as 1‐(2‐aminoethyl)piperazine, N‐methyl‐1,3‐propanediamine, or N‐ethylethylenediamine. When the ratio of diacrylate to diamine was 1/1, no gelation was observed throughout the polymerization. When the ratio of diacrylate to diamine was 3/2, no crosslinking occurred in the diluted solution, whereas an insoluble network formed in the concentrated solution. Fourier transform infrared and mass spectrometry were used to investigate the reaction procedure. The secondary amino group of diamine reacted faster with the vinyl group of diacrylate; this resulted in the formation of the intermediate with an acrylate group and two active hydrogen atoms attached to a nitrogen atom. Further self‐polyaddition of the intermediate, a kind of AB2‐type monomer, gave the hyperbranched poly(ester amine). © 2002 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 40: 2340–2349, 2002
Structure, orientation, and conformation of adsorbed polyamides
Authors: Elzein Tamara , Brogly Maurice , Castelein Gilles , Schultz Jacques
Published: October 2002

The structural properties and interfacial organization of polyamides adsorbed as thin films were investigated. Polarization‐modulation infrared reflection–absorption spectroscopy was used first to identify the crystalline structure of adsorbed layers and to reveal the conformation and orientation of adsorbed chains. The influence on the structure and molecular orientation of the number of carbon atoms in the aliphatic chain of the diacid part was investigated (PA 66, 610, and 612). The effect of the substrate surface chemistry was also examined. Gold substrates are either inert or functionalized with OH groups. Grafting of the OH functions did not affect the orientation of chains that apparently lay rather parallel to the interface, whereas the crystalline morphology was dependent on the substrate chemical functionality. Knowledge of the structure and orientation of chains adsorbed at an interface was of fundamental importance for the prediction of adhesive strength, that is, the final performance of these latter depended strongly on the properties of the interface formed between the solids brought into contact. © 2002 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 40: 1464–1476, 2002
Novel application of biological glue in the management of a complicated pneumothorax in cystic fibrosis
Authors: Garske Luke A. , Tam Robert K.W. , Windsor Morgan F. , Bell Scott C.
Published: October 2002

Spontaneous pneumothorax is a frequent complication in advanced lung disease of cystic fibrosis. We describe a case of a complicated pneumothorax in a 21‐year old‐woman with cystic fibrosis who was effectively treated with the application of biological glue via a minithoracotomy. Pediatr Pulmonol. 2002; 34:138–140. © 2002 Wiley‐Liss, Inc.
Effects of variable concentrations of inhaled nitric oxide and oxygen on the lungs of newborn piglets
Authors: Levine Carolyn Robbins , Kazzaz Jeffrey A. , Koo Hsi‐Chi , Chester Darrin , Merritt T. Allen , Matalon Sadis , Pollack Simcha , Davis Jonathan M.
Published: October 2002

We previously demonstrated that inhalation of high concentrations of nitric oxide (iNO) and oxygen for 48 hr causes significant lung injury in newborn piglets. To determine if these effects persist at lower concentrations, groups of newborn piglets were mechanically ventilated for 48 hr with (study 1) constant O2 (90–100%) and decreasing iNO (100–2 ppm) or (study 2) constant iNO (50 ppm) and decreasing O2 (95–30%). Bronchoalveolar lavage (BAL) fluid was assayed for surfactant function, and markers of lung inflammation and physiologic parameters were monitored.

Neutrophil chemotactic activity (NCA), % neutrophils, and total protein (TP) concentrations decreased significantly in BAL fluid of study 1 piglets as iNO was reduced and inhaled oxygen fraction remained constant, indicating less pulmonary injury at low iNO levels. Low‐dose iNO (2 ppm) did not have antiinflammatory effects. However, surfactant function was minimally affected by lowering iNO, and was abnormal in all groups. In contrast, in study 2, pulmonary inflammation and injury were lower when O2 was decreased to 70% or less, with iNO constant at 50 ppm. Surfactant function normalized and oxygenation improved in study 2 piglets when the inhaled oxygen fraction was decreased and iNO remained constant.

These data suggest that iNO‐ and O2‐induced lung injury may be minimized by weaning O2 or iNO, although better physiologic function may be obtained when iNO concentrations are constant and O2 is reduced. This has important implications in the clinical management of critically ill newborns treated with O2 and iNO for pulmonary disorders. Pediatr Pulmonol. 2002; 34:58–65. © 2002 Wiley‐Liss, Inc.
Pulmonary lipoblastoma in an 18‐month‐old child: A unique tumor in children
Authors: Kanu Ada , Oermann Christopher M. , Malicki Denise , Wagner Milton , Langston Claire
Published: October 2002

Lipoblastoma, a rare benign tumor of adipose tissue, typically occurs in the superficial or deep layers of soft tissue on the trunk or extremities. Other sites of occurrence include the head, neck, and retroperitoneum. Lipoblastoma of the chest wall and parietal pleural have been reported, but occurrence within the lung has not been previously described. We report a case of pulmonary lipoblastoma in a young child presenting with complete opacification of the left hemithorax and mediastinal shift on chest radiograph. A lobectomy was performed, and the diagnosis was made by histological examination. Pediatr Pulmonol. 2002; 34:150–154. © 2002 Wiley‐Liss, Inc.
Outcome in adulthood of asymptomatic airway hyperresponsiveness in childhood: A longitudinal population study
Authors: Rasmussen Finn , Taylor D. Robin , Flannery Erin M. , Cowan Jan O. , Greene Justina M. , Herbison G. Peter , Sears Malcolm R.
Published: October 2002

The clinical outcome of asymptomatic airway hyperresponsiveness (AHR) first detected in childhood is sparsely reported, with conflicting results. We used a birth cohort of 1,037 children followed to age 26 years to assess the clinical outcome of asymptomatic AHR to methacholine first documented in study members at age 9 years.

Of 547 study members who denied wheezing symptoms ever at age 9 years, 41 (7.5%) showed AHR. Forty showed methacholine responsiveness, with a provocation concentration of methacholine that elicted a 20% drop in forced expired volume in 1 sec (PC20) ≤ 8 mg/mL, and one had baseline airway obstruction with a bronchodilator response exceeding 10%. Of these 41 study members, 18 (44%), 11 (27%), and 4 (10%) maintained AHR in 1, 2, and 3 later assessments, respectively, while 23 (56%) manifested AHR only at age 9. Compared with asymptomatic study members without AHR, those with asymptomatic AHR at age 9 years were more likely to report asthma and wheeze at any subsequent assessment, were more likely to have high IgE levels and eosinophils at ages 11 and 21, and more often demonstrated positive responses to skin allergen testing at ages 13 and 21 years. Persistent AHR at later assessments increased these likelihoods further.

In conclusion, asymptomatic children with AHR are more likely to develop asthma and atopy later in life compared with asymptomatic children without AHR. Persistent AHR, even though initially asymptomatic, was associated with an even greater increased risk of development of asthma. We suggest that rather than considering AHR as a marker of asthma, it should be regarded as a parallel pathological process that may lead to subsequent symptoms and clinical evidence of asthma. Pediatr Pulmonol. 2002; 34:164–171. © 2002 Wiley‐Liss, Inc.
Series of laryngomalacia, tracheomalacia, and bronchomalacia disorders and their associations with other conditions in children
Authors: Masters I.B. , Chang A.B. , Patterson L. , Wainwright C. , Buntain H. , Dean B.W. , Francis P.W.
Published: October 2002

Laryngomalacia, bronchomalacia, and tracheomalacia are commonly seen in pediatric respiratory medicine, yet their patterns and associations with other conditions are not well‐understood. We prospectively video‐recorded bronchoscopic data and clinical information from referred patients over a 10‐year period and defined aspects of interrelationships and associations.

Two hundred and ninety‐nine cases of malacia disorders (34%) were observed in 885 bronchoscopic procedures. Cough, wheeze, stridor, and radiological changes were the most common symptoms and signs. The lesions were most often found in males (2:1) and on the left side (1.6:1). Concomitant malacia lesions ranged from 24% for laryngotracheobronchomalacia to 47% for tracheobronchomalacia. The lesions were found in association with other disorders such as congenital heart disorders (13.7%), tracheo‐esophageal fistula (9.6%), and various syndromes (8%).

Even though the understanding of these disorders is in its infancy, pediatricians should maintain a level of awareness for malacia lesions and consider the possibility of multiple lesions being present, even when one symptom predominates or occurs alone. Pediatr Pulmonol. Pediatr Pulmonol. 2002; 34:189–195. © 2002 Wiley‐Liss, Inc.
Resveratrol induces apoptosis in LNCaP cells and requires hydroxyl groups to decrease viability in LNCaP and DU 145 cells
Authors: Morris Gary Z. , Williams Roy L. , Elliott Mark S. , Beebe Stephen J.
Published: October 2002

BACKGROUND

This study was conducted to determine the effects of resveratrol on prostate cancer cell viability through apoptosis induction and the significance of the three hydroxyl groups on resveratrol to the measured effect.

METHODS

Hormone‐sensitive LNCaP cells and hormone‐insensitive DU 145 cells were treated with resveratrol, tri‐methoxy‐resveratrol, or diethylstilbestrol (DES; the positive control for toxicity and apoptosis). Cell viability was determined by using an MTS assay. Apoptosis was determined by the appearance of apoptotic morphology, annexin V‐FITC–positive intact cells, and caspase activation.

RESULTS

Resveratrol and DES decreased viability in LNCaP cells, but only resveratrol‐treated cells expressed apoptotic morphology, annexin V‐FITC–positive cells, and caspase activation. Tri‐methoxy‐resveratrol had no effect on DU 145 cell‐viability and was less toxic to LNCaP cells than resveratrol.

CONCLUSION

Resveratrol was toxic to cells regardless of whether the cells were hormone‐responsive or ‐unresponsive. This finding suggests that the cell's hormone responsive status is not an important determinant of the response to resveratrol. Furthermore, the hydroxyl‐groups on resveratrol are required for cell toxicity. Finally resveratrol but not DES induced caspase‐mediated apoptosis. Prostate 52: 319–329, 2002. © 2002 Wiley‐Liss, Inc.
Completion and refinement of 3‐D homology models with restricted molecular dynamics: Application to targets 47, 58, and 111 in the CASP modeling competition and posterior analysis
Authors: Flohil J.A. , Vriend G. , Berendsen H.J.C.
Published: October 2002

A method is presented to refine models built by homology by the use of restricted molecular dynamics (MD) techniques. The basic idea behind this method is the use of structure validation software to determine for each residue the likelihood that it is modeled correctly. This information is used to determine constraints and restraints in an MD simulation including explicit solvent molecules, which is used for model refinement. The procedure is based on the idea that residues that the validation software identifies as correctly positioned should be strongly constrained or restrained in the MD simulations, whereas residues that are likely to be positioned wrongly should move freely. Two different protocols are compared: one (applied to CASP3 target T58) using full structural constraints with separate optimization of each short fragment and the other (applied to T47) allowing some freedom using harmonic restraining potentials, with automatic optimization of the whole molecule. Structures along the MD trajectory that scored best in structural checks were selected for the construction of models that appeared to be successful in the CASP3 competition. Model refinement with MD in general leads to a model that is less like the experimental structure (Levitt et al. Nature Struct Biol 1999;6:108–111). Actually, refined T47 was slightly improved compared to the starting model; changes in model T58 led not to further enhancement. After the X‐ray structure of the modeled proteins became known, the procedure was evaluated for two targets (T47 and the CASP4 target T111) by comparing a long simulation in water with the experimental target structures. It was found that structural improvements could be obtained on a nanosecond time scale by allowing appropriate freedom in the simulation. Structural checks applied to fast fluctuations do not appear to be informative for the correctness of the structure. However, both a simple hydrogen bond count and a simple compactness measure, if averaged over times of typically 300 ps, correlate well with structural correctness and we suggest that criteria based on these properties may be used in computational folding strategies. Proteins 2002;48:593–604. © 2002 Wiley‐Liss, Inc.
MIAX: A new paradigm for modeling biomacromolecular interactions and complex formation in condensed phases
Authors: Del Carpio‐Muñoz Carlos Adriel , Ichiishi Eiichiro , Yoshimori Atsushi , Yoshikawa Toshikazu
Published: October 2002

A new paradigm is proposed for modeling biomacromolecular interactions and complex formation in solution (protein–protein interactions so far in this report) that constitutes the scaffold of the automatic system MIAX (acronym for Macromolecular Interaction Assessment X). It combines in a rational way a series of computational methodologies, the goal being the prediction of the most native‐like protein complex that may be formed when two isolated (unbound) protein monomers interact in a liquid environment. The overall strategy consists of first inferring putative precomplex structures by identification of binding sites or epitopes on the proteins surfaces and a simultaneous rigid‐body docking process using geometric instances alone. Precomplex configurations are defined here as all those decoys the interfaces of which comply substantially with the inferred binding sites and whose free energy values are lower. Retaining all those precomplex configurations with low energies leads to a reasonable number of decoys for which a flexible treatment is amenable. A novel algorithm is introduced here for automatically inferring binding sites in proteins given their 3‐D structure. The procedure combines an unsupervised learning algorithm based on the self‐organizing map or Kohonen network with a 2‐D Fourier spectral analysis. To model interaction, the potential function proposed here plays a central role in the system and is constituted by empirical terms expressing well‐characterized factors influencing biomacromolecular interaction processes, essentially electrostatic, van der Waals, and hydrophobic. Each of these procedures is validated by comparing results with observed instances. Finally, the more demanding process of flexible docking is performed in MIAX embedding the potential function in a simulated annealing optimization procedure. Whereas search of the entire configuration hyperspace is a major factor precluding hitherto systems from efficiently modeling macromolecular interaction modes and complex structures, the paradigm presented here may constitute a step forward in the field because it is shown that a rational treatment of the information available from the 3‐D structure of the interacting monomers combined with conveniently selected computational techniques can assist to elude search of regions of low probability in configuration space and indeed lead to a highly efficient system oriented to solve this intriguing and fundamental biologic problem. Proteins 2002;48:696–732. © 2002 Wiley‐Liss, Inc.
Comparison of sequence and structure alignments for protein domains
Authors: Marchler‐Bauer Aron , Panchenko Anna R. , Ariel Naomi , Bryant Stephen H.
Published: October 2002

Profile search methods based on protein domain alignments have proven to be useful tools in comparative sequence analysis. Domain alignments used by currently available search methods have been computed by sequence comparison. With the growth of the protein structure database, however, alignments of many domain pairs have also been computed by structure comparison. Here, we examine the extent to which information from these two sources agrees. We measure agreement with respect to identification of homologous regions in each protein, that is, with respect to the location of domain boundaries. We also measure agreement with respect to identification of homologous residue sites by comparing alignments and assessing the accuracy of the molecular models they predict. We find that domain alignments in publicly available collections based on sequence and structure comparison are largely consistent. However, the homologous regions identified by sequence comparison are often shorter than those identified by 3D structure comparison. In addition, when overall sequence similarity is low alignments from sequence comparison produce less accurate molecular models, suggesting that they less accurately identify homologous sites. These observations suggest that structure comparison results might be used to improve the overall accuracy of domain alignment collections and the performance of profile search methods based on them. Proteins 2002;48:439–446. © 2002 Wiley‐Liss, Inc.
Inhibitory effects of Keishi‐bukuryo‐gan on free radical induced lysis of rat red blood cells
Authors: Sekiya Nobuyasu , Goto Hirozo , Shimada Yutaka , Terasawa Katsutoshi
Published: October 2002

Keishi‐bukuryo‐gan (KBG) prevents the progression of atherosclerosis in cholesterol‐fed rabbits by its antioxidative effect. The present study was to test our hypothesis that ingestion of KBG would protect red blood cell (RBC) membranes from free radical induced oxidation if polyphenolic antioxidants in KBG could be absorbed and circulated in the blood. When incubated with a RBC suspension, KBG and four of five herb medicines constituting KBG provided strong protection for RBC membranes against haemolysis induced by 2,2‐azo‐bis (2‐amidinopropane) dihydrochloride (AAPH), an azo free radical initiator. The inhibitory effect was dose dependent at concentrations of 100–1000 μg/mL. Furthermore, the ingestion of 200 mg of KBG was associated with a significant decrease in susceptibility of RBC to haemolysis in rats. Copyright © 2002 John Wiley & Sons, Ltd.
Packaging information needed for evaluation in the supply chain: the case of the Swedish grocery retail industry
Authors: Saghir Mazen
Published: October 2002

The proper use and exchange of the right packaging‐related information in a grocery supply chain is critical to achieve an efficient and responsive packaging logistics system. The use of well‐defined packaging‐related information that is available for all actors in the supply chain also facilitates an integrated and supply chain‐orientated packaging development. The objective of this paper is to describe and identify the packaging‐related information used in the grocery retail industry. The paper also describes and analyses how the information is used in the supply chain, with focus on the packaging evaluation process. Case and field studies involving six companies from the Swedish grocery industry were conducted to identify the parameters used and shared among them. The paper discusses what kind of information is required to properly evaluate a packaging concept, what parameters are missing and how the information should be used in the supply chain. Finally, the paper suggests a procedure for packaging logistics performance with required parameters. Copyright © 2002 John Wiley & Sons, Ltd.
Privacy protection, health care and quality control
Authors: Bruppacher Rudolf
Published: October 2002

In the past three decades, patient rights on the one hand, and health care and research activities in health services on the other hand, have experienced unprecedented development. Requirements of privacy protection, particularly the restrictions on ‘secondary analysis’ of health data, have become a problem in an increasingly complex health care environment and have become a hindrance to research. Legal regulations have developed differently in different countries. Recent attempts, such as the European Community directive on privacy protection promise effective harmonization, at least for developed countries. However, many questions regarding their interpretation remain and they are discussed in this article. Copyright © 2002 John Wiley & Sons, Ltd.
Characterizing stateful resource attacks using modeling and simulation
Authors: Gregg Donna , Blackert William , Heinbuch David , Furnanage Donna , Kouskoulas Yanni
Published: October 2002

Denial of Service (DoS) attacks come in a variety of types and can target groups of users, individual users or entire computer systems. With the ever‐increasing reliance on networked information systems for command and control of military systems—not to mention communications infrastructures—relatively simple attacks that degrade or deny service can have devastating effects. We have modeled and validated a variety of DoS attacks and have executed these models against a validated target network model, whose architecture and stochastic behavior is varied for analysis purposes. We have conducted a systems analysis using these models and have characterized attack effects. This paper describes the analysis of two attacks, each of which consumes resources at a server. Output from our model includes the probability of denied service and service time under attack and no attack conditions. Our objective is to identify attack classes and characterize attack behavior within a class, so that the behavior of new attacks falling within a class can be anticipated and defended against. Copyright © 2002 John Wiley & Sons, Ltd.
Singlet‐singlet annihilation in ultraviolet matrix‐assisted laser desorption/ionization studied by fluorescence spectroscopy
Authors: Lüdemann Hans‐Christian , Redmond Robert W. , Hillenkamp Franz
Published: October 2002

Laser‐induced fluorescence spectroscopy was carried out on microcrystalline samples of three typical matrices under conditions of matrix‐assisted laser desorption/ionization (MALDI). The emitted fluorescence intensity was determined as a function of incident laser fluence and a sublinear increase of the fluorescence intensity with laser fluence was found. A very good fit was obtained when the experimental fluorescence vs. fluence data were compared with a numerical model assuming that under typical MALDI fluence conditions a large fraction of molecules in the excited singlet state undergoes singlet‐singlet annihilation. Throughout the fluence range relevant for MALDI, however, the experimental data could not be fit well to a model assuming resonant two‐photon absorption as the process depopulating the singlet state. In a separate set of experiments, the singlet lifetimes of several typical crystalline MALDI matrices were determined and found to be considerably shorter than previously reported. While both singlet‐singlet annihilation and resonant two‐photon absorption have been discussed in the literature as candidates for pathways to primary matrix ion generation in MALDI, the data presented here suggest that singlet‐singlet annihilation is the dominant mechanism for depopulating the singlet state in a matrix crystal excited at typical MALDI fluences. Copyright © 2002 John Wiley & Sons, Ltd.
Sample preparation in matrix‐assisted laser desorption/ionization mass spectrometry of whole bacterial cells and the detection of high mass (>20 kDa) proteins
Authors: Vaidyanathan Seetharaman , Winder Catherine L. , Wade Steve C. , Kell Douglas B. , Goodacre Royston
Published: October 2002

Three sample preparation strategies commonly employed in matrix‐assisted laser desorption/ionization mass spectrometry (MALDI‐TOFMS) of whole bacterial cells were investigated for the detection of high mass signals; these included the dried droplet, the seed‐layer/two‐layer, and the bottom‐layer methods. Different sample preparation approaches favoured the detection of high‐ or low‐mass proteins. The low‐mass peaks were best detected using the bottom‐layer method. By contrast, the dried droplet method using a solvent with higher water content, and hence effecting a slower crystallization process, gave the best results for the detection of high‐mass signals. Signals up to m/z 158 000 could be detected with this methodology for Bacillus sphaericus. Sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS‐PAGE) analysis of the same extracts used for MALDI‐TOFMS showed bands in the molecular weight range in which high‐mass peaks were observed in MALDI‐MS, suggesting that the high‐mass signals are not polymeric adducts of low‐mass protein monomers. In addition, one of the high molecular weight proteins (∼126 kDa) was putatively identified as an S‐layer protein by an in‐gel tryptic digest. The bacterial samples spotted on the target wells for MALDI‐TOFMS, using the different sample preparation strategies, were examined under a scanning electron microscope and differences were observed between the different strategies, suggesting that the nature of the crystals and the distribution of the analytes amidst the crystals could influence the spectral pattern observed in MALDI‐TOFMS of whole bacterial cells. Finally, evidence is presented to indicate that, although the determinands are intact cells, cell lysis occurs both before and during the MALDI process. Copyright © 2002 John Wiley & Sons, Ltd.
A rapid and precise technique for measuring δ13C‐CO2 and δ18O‐CO2 ratios at ambient CO2 concentrations for biological applications and the influence of container type and storage time on the sample isotope ratios
Authors: Mortazavi Behzad , Chanton Jeffrey P.
Published: October 2002

A simple modification to a commercially available gas chromatograph isotope ratio mass spectrometer (GC/IRMS) allows rapid and precise determination of the stable isotopes (13C and 18O) of CO2 at ambient CO2 concentrations. A sample loop was inserted downstream of the GC injection port and used to introduce small volumes of air samples into the GC/IRMS. This procedure does not require a cryofocusing step and significantly reduces the analysis time. The precisions for δ13C and δ18O of CO2 at ambient concentration were ±0.164 and ±0.247‰, respectively. This modified GC/IRMS was used to test the effects of storage on the 18O and 13C isotopic ratios of CO2 at ambient concentrations in four container types. On average, the change in the 13C‐CO2 and 18O‐CO2 ratios of samples after one week of storage in glass vials equipped with butyl rubber stoppers (Bellco Glass Inc.) were depleted by 0.12 and by 0.20‰, respectively. The 13C ratios in aluminum canisters (Scotty II and IV, Scott Specialty Gasses) after one month of storage were depleted, on average, by 0.73 and 2.04‰, respectively, while the 18O ratios were depleted by 0.38 and 1.20‰ for the Scotty II and IV, respectively. After a month of storage in electropolished containers (Summa canisters, Biospheric Research Corporation), the 13C‐CO2 and 18O‐CO2 ratios were depleted, on average, by 0.26 and enriched by 0.30‰, respectively, close to the precision of measurements. Samples were collected at a mature hardwood forest for CO2 concentration determination and isotopic analysis. A comparison of CO2 concentrations determined with an infrared gas analyzer and from sample voltages, determined on the GC/IRMS concurrent with the isotopic analysis, indicated that CO2 concentrations can be determined reliably with the GC/IRMS technique. The 13C and 18O ratios of nighttime ecosystem‐respired CO2, determined from the intercept of Keeling plots, were −26.11‰ (V‐PDB) and −8.81‰ (V‐PDB‐CO2), respectively. Copyright © 2002 John Wiley & Sons, Ltd.