bluuebunny/crossref_metadata_2025 huggingface dataset:
Can schoolchildren provide valid answers about their respiratory health experiences in questionnaires? Implications for epidemiological studies
Authors: Yu Tak‐sun Ignatius , Wong Tze‐wai
Published: December 2003

To evaluate the relative validity of information on children's respiratory experience given by different informants, we examined and compared the relationship between low ventilatory function (defined as more than 1 standard deviation below the corresponding mean) and schoolchildren's respiratory symptoms or illnesses reported separately by the children and their parents, using a standard respiratory questionnaire. A total of 1,963 children aged 8–12 years from 12 primary schools in three districts of Hong Kong provided parent‐completed and self‐completed questionnaires, as well as acceptable spirometric measurements. Prevalence of low forced expiratory volume ratio (FEV1/FVC) and low forced expiratory flow rate between 25–75% of FVC (FEF25–75) were higher among those with either parent or child‐reported symptoms/illnesses. Child‐reported cough and phlegm performed better than the corresponding parent‐reported symptoms in predicting low FEV1/FVC. The contrary was true for wheezing and bronchitis. For low FEF25–75, parent‐reported wheezing, asthma, and bronchitis performed better, while the opposite was true for cough. Subgroup analysis by age showed that for older children (age 10 or above), child‐reported symptoms/illnesses performed better in general in the prediction of low FEV1/FVC. On the other hand, parent‐reported symptoms/illnesses seemed to have an advantage over child‐reported ones in predicting low FEF25–75. Subgroup analysis by sex did not reveal any clear pattern. Overall, there was little difference between respiratory illness experiences reported by schoolchildren and their parents in terms of their associations with low ventilatory function. In a population‐based study in which schoolchildren are subjects, it would be appropriate for respiratory questionnaires to be administered to the children themselves, especially if they have reached age 10. By doing so, higher response rates, and perhaps also better yields of correct information, may be obtained. Pediatr Pulmonol. 2004; 37:37–42. © 2004 Wiley‐Liss, Inc.
Variation of peak inspiratory flow through dry powder inhalers in children with stable and unstable asthma
Authors: Kamps Arvid W.A. , Brand Paul L.P. , Roorda Ruurd Jan
Published: December 2003

Drug release from dry powder inhalers depends for a large part on a sufficiently high peak inspiratory flow (PIF). We determined the variation of PIF through two commonly prescribed dry powder inhalers in children with asthma. We analyzed the effect of inhaler device, age, and severity of asthma symptoms on variation of PIF. Fifty‐eight children with asthma (4–15 years old) recorded PIF values together with asthma symptoms in a diary twice daily for 4 weeks. PIF was measured with a portable PIF‐meter (In‐Check™) equipped with adapters to simulate flow resistance through the Accuhaler™ and Turbohaler™ inhalers. Children generated higher PIF values through an Accuhaler adapter than through a Turbohaler adapter (95% CI for difference, 25.7–31.7). Mean PIF values increased with age, independent of type of inhaler. The mean (SD) variation of PIF (low%high) was 72.3 (8.1)% for patients using the Accuhaler adapter, and 67.0 (14.5)% for patients using the Turbohaler adapter (mean difference, 5.2%; 95% CI, −0.9 to 11.4). Children ≤7 years of age had a significantly greater variation of PIF in addition to a lower mean PIF (P = 0.0003). PIF decreased significantly when symptoms of asthma increased (mean maximal decrease 11 l/min; P < 0.01), but the correlation between PIF and morning and evening symptoms was weak (r = −0.18 and r = −0.16, respectively). Patients who reported moderate or severe symptoms during the study period had a significantly greater variation of PIF compared to patients who remained free of symptoms or reported mild symptoms. The majority of patients generated PIF >30 l/min during the study, even when they experienced symptoms of asthma. The variation of PIF through the Accuhaler and Turbohaler adapter was significantly greater for children ≤7 years of age and for patients experiencing moderate or severe symptoms of asthma. Pediatr Pulmonol. 2004; 37:65–70. © 2004 Wiley‐Liss, Inc.
Proliferation of prostate cancer cells and activity of neutral endopeptidase is regulated by bombesin and IL‐1β with IL‐1β acting as a modulator of cellular differentiation
Authors: Albrecht Martin , Doroszewicz Jolanta , Gillen Sonja , Gomes Iara , Wilhelm Beate , Stief Thomas , Aumüller Gerhard
Published: December 2003

BACKGROUND

Neutral endopeptidase (NEP) is a cell‐surface bound enzyme that cleaves and inactivates neuropeptides such as bombesin and substance P and is involved in the transition from hormonally regulated androgen‐dependent prostate cancer (PC) to androgen‐independent PC. Neuropeptides are implicated in growth regulation of different cell types and function as transmitters between the neuroendocrine and the immune system.

METHODS

NEP‐expression, enzymatic activity of the membrane bound protein, cell proliferation, procalcitonin (PCT) production, and secretion as well as changes in cell morphology of prostatic cells were evaluated after treatment with the immunomodulatory cytokine interleukin‐1β (IL‐1β), neuropeptides (bombesin, substance P), and neuropeptide‐conditioned media derived from a human neuroendocrine cell line.

RESULTS

Incubation of LNCaP tumor cells with IL‐1β resulted in a diminished proliferative activity, induction of neurite‐like outgrowth which was accompanied by the formation of tubular‐type mitochondria typical for neuronal/neuroendocrine cells, and an increased production and secretion of PCT. Conversely, proliferation of prostatic stromal cells was enhanced by the cytokine coming along with an increased number of Golgi‐apparatuses and ER‐cisternae. Bombesin had an antimitotic effect on LNCaP, but not on stromal cells. Substance P did not influence the growth of any of the cell types investigated, whereas neuropeptide‐conditioned media exerted a slightly mitogenic effect on both cell types. The activity of LNCaP cell‐surface bound NEP was enhanced by bombesin, but was diminished by substance P and neuropeptide‐conditioned media.

CONCLUSIONS

Proliferation and activity of neuropeptide degrading NEP is regulated differently by immunomodulatory substances in PC cells and cells derived from the prostatic stroma with IL‐1β being a potent modulator of cellular differentiation and a potential target for anticancer drug design in PC cells. © 2003 Wiley‐Liss, Inc.
Association between captopril, other antihypertensive drugs and risk of prostate cancer
Authors: Ronquist Gunnar , Rodríguez Luis Alberto García , Ruigómez Ana , Johansson Saga , Wallander Mari‐Ann , Frithz Göran , Svärdsudd Kurt
Published: December 2003

BACKGROUND

There has been some debate on the existence of an association between hypertension, antihypertensive medications and cancer risk.

METHODS

We performed a nested case‐control study to assess the association between the risk of prostate cancer and the use of the angiotensin converting enzyme (ACE)‐inhibitor captopril, and other antihypertensive drugs. We used data from the General Practice Research Database in UK.

RESULTS

We found an incidence rate of prostate cancer of 1.61 per 1,000 person‐years among male patients aged 50–79 years old. Patients with a history of benign prostatic hyperplasia and/or prostatism carried a two‐fold greater risk of prostate cancer than those without such antecedents. None of the other studied co‐morbidities were associated with prostate cancer. We found that users of captopril had a relative risk of 0.7 (95% CI: 0.4–1.2) to develope prostate cancer. None of the other studied individual ACE‐inhibitors shared a similar effect with the one observed for captopril.

CONCLUSIONS

No clear association was apparent between the use of antihypertensive drugs and prostate cancer. However, specific focus on users of captopril showed a lower risk of subsequent prostate cancer. Further research is needed to explore this association. © 2003 Wiley‐Liss, Inc.
Chronic activity of ectopic type 1 fibroblast growth factor receptor tyrosine kinase in prostate epithelium results in hyperplasia accompanied by intraepithelial neoplasia
Authors: Wang Fen , McKeehan Kerstin , Yu Chundong , Ittmann Michael , McKeehan Wallace L.
Published: December 2003

BACKGROUND

Ectopic expression of fibroblast growth factor receptor 1 (FGFR1) tyrosine kinase in epithelial cells is associated with progression of prostate cancer. Ectopic expression by transfection of FGFR1 in premalignant epithelial cells from nonmalignant Dunning tumors accelerated time‐dependent progression of epithelial cells to malignancy. This study was designed to test the effect of chronic androgen‐dependent ectopic activity of FGFR1 in the normal adult mouse epithelium by gene targeting.

MATERIALS AND METHODS

Constitutively active FGFR1 (caFGFR1) was targeted to prostate epithelial cells using the androgen‐dependent probasin (PB) promoter. Prostate tissues of three strains were characterized over a period of 2 years by HE staining, immunohistochemical analyses for cytokeratin and α‐actin, and rate of androgen‐induced regeneration after castration.

RESULTS

Relative to wildtype littermates, transgenic mice showed increased overall size, hyperplasia in epithelial, and, to a lesser extent, stromal compartments and nuclear atypia in epithelial cells of the prostate with increasing age. Androgen‐induced regeneration after castration was enhanced at day 3 by two‐fold in mice expressing ectopic caFGFR1.

CONCLUSIONS

The ectopic presence and chronic activation of FGFR1 in mouse prostate epithelial cells induces progressive prostate intraepithelial neoplasia. These results confirm results suggested by the transplantable Dunning tumor and cell culture models that, in contrast to homeostasis‐promoting resident FGFR2, chronic ectopic FGFR1 kinase activity in the epithelium disrupts homeostasis between stroma and epithelium. Although insufficient alone, it may cooperate with other oncogenic changes to promote epithelial cells down the path to malignancy. © 2003 Wiley‐Liss, Inc.
Neutralizing VEGF bioactivity with a soluble chimeric VEGF‐receptor protein flt(1‐3)IgG inhibits testosterone‐stimulated prostate growth in castrated mice
Authors: Lissbrant Ingela Franck , Hammarsten Peter , Lissbrant Erik , Ferrara Napoleone , Rudolfsson Stina Häggström , Bergh Anders
Published: December 2003

BACKGROUND

Recent studies show that testosterone‐stimulated growth of the glandular tissue in the ventral prostate in adult castrated rats is preceded by increased epithelial VEGF synthesis, endothelial cell proliferation, vascular growth, and increased blood flow. These observations suggest that testosterone‐stimulated prostate growth could be angiogenesis dependent, and that VEGF could play a central role in this process.

METHODS

Adult male mice were castrated and after 1 week treated with testosterone and vehicle, or with testosterone and a soluble chimeric VEGF‐receptor flt(1‐3)IgG protein.

RESULTS

Treatment with testosterone markedly increased endothelial cell proliferation, vascular volume, and organ weight in the ventral prostate lobe in the vehicle groups, but these responses were inhibited but not fully prevented by anti‐VEGF treatment. The testosterone‐stimulated increase in epithelial cell proliferation was unaffected by flt(1‐3)IgG, but endothelial and epithelial cell apoptosis were increased in the anti‐VEGF compared to the vehicle‐treated groups.

CONCLUSIONS

This study suggests that testosterone stimulates vascular growth in the ventral prostate lobe indirectly by increasing epithelial VEGF synthesis and that this is a necessary component in testosterone‐stimulated prostate growth. © 2003 Wiley‐Liss, Inc.
Messenger RNA levels and enzyme activities of 5 alpha‐reductase types 1 and 2 in human benign prostatic hyperplasia (BPH) tissue
Authors: Shirakawa Toshiro , Okada Hiroshi , Acharya Bishnu , Zhang Zhujun , Hinata Nobuyuki , Wada Yoshitaka , Uji Tatsuya , Kamidono Sadao , Gotoh Akinobu
Published: December 2003

BACKGROUND

Benign prostatic hyperplasia (BPH) development requires testicular androgens and aging. The principle prostatic androgen is dihydrotestosterone (DHT). Testosterone is converted to DHT by the enzyme 5 alpha‐reductase. Two distinct 5 alpha‐reductase enzymes, types 1 and 2, have been identified. While some studies have suggested that type 2 isoenzyme predominates in the prostate, studies on the prostatic localization of the two isoenzymes are controversial. The purpose of this study was to determine the quantitative expressions of 5 alpha‐reductase types 1 and 2 in BPH tissues.

METHODS

We examined the localizations of types 1 and 2 isoenzymes in BPH tissues using immunohistochemical staining and a real‐time quantitative RT‐PCR assay using the TaqMan system. We measured the enzyme activities of types 1 and 2 at pH values of 7.5 and 5.0, respectively.

RESULTS

Our immunohistochemical study showed that type 1 isoenzyme was expressed predominantly in epithelial cells, whereas type 2 isoenzyme was expressed in both stromal and epithelial cells. The real‐time RT‐PCR assay demonstrated that the copy numbers of type 1 isoenzyme mRNA were significantly higher than those of type 2 isoenzyme mRNA. There were significant associations between enzyme activity at pH 7.5 and type 1 isoenzyme mRNA expression, and between the activity at pH 5.0 and type 2 mRNA expressions.

CONCLUSIONS

We demonstrated that 5 alpha‐reductase type 1 had a specific enzyme activity in the prostate, which supports the hypothesis that the type 1 isoenzyme may play a significant role in maintaining prostate enlargement along with the type 2 isoenzyme. © 2003 Wiley‐Liss, Inc.
Characterization of a transplantable hormone‐responsive human prostatic cancer xenograft TEN12 and its androgen‐resistant sublines
Authors: Harper Maureen E. , Goddard Lindy , Smith Christopher , Nicholson Robert I.
Published: December 2003

BACKGROUND

Models for human prostate cancer can facilitate the study of resistance to endocrine therapy, aid drug discovery, and pre‐clinical assessment.

METHODS

Characteristics thought relevant to the growth in athymic nude mice of TEN12, an androgen‐dependent transplantable prostatic cell line derived from a primary prostate carcinoma, and its two androgen‐independent sublines, TEN12F and TEN12C, have been assessed immunocytochemically.

RESULTS

The xenografts of the parental TEN12 line are moderately differentiated with both papillary and glandular regions, pleomorphic nuclei and abundant mitotic figures and are extremely vascular. The cells express androgen receptor (AR), PSA, VEGF, EGFR, c‐erbB2, and TGFα. Both TEN12F and TEN12C xenografts possessed a more anaplastic morphology and displayed significantly lower growth rates, reduced blood vessel density (BVD), decreased MIB‐1 antigen and E‐cadherin expression and increased cytoplasmic AR and HSP90 staining. Elevated EGFR (membrane) but not c‐erbB2 expression was demonstrated in the TEN12F line only. Castration of mice bearing TEN12 xenografts rapidly induced the appearance of cytoplasmic AR in the cells, PSA levels decreased initially but recovered to below pre‐castration levels whilst reduced TGFα and loss of VEGF expression was seen in the long‐term castrates.

CONCLUSIONS

TEN12 and its sublines offer additional in vivo models to study the factors involved in the progression of prostatic cancer to androgen‐independence. © 2003 Wiley‐Liss, Inc.
Effect of a short CAG (glutamine) repeat on human androgen receptor function
Authors: Ding Dacheng , Xu Lihua , Menon Mani , Reddy G. Prem Veer , Barrack Evelyn R.
Published: December 2003

BACKGROUND

The human androgen receptor (AR) gene contains an uninterrupted CAG repeat that is polymorphic in length in the general population (range, 11–31 CAG's; median, 21). The CAG repeat encodes a glutamine repeat in the N‐terminal transactivation domain of the AR protein. We previously reported that a 17‐CAG AR gene was much more common in a cohort of men with prostate cancer (8.5%) than in the general European American population (1.3%). This suggested that a 17‐CAG repeat may have pathophysiological consequences. The goal of the present study was to directly test the hypothesis that a 17‐CAG repeat might uniquely affect androgen action in human prostate cancer cells.

METHODS

DU145 cells, lacking endogenous AR, were transiently transfected with an AR expression plasmid (with a CAG repeat ranging in length from 14 to 25) and an androgen‐responsive reporter plasmid (PSA‐luciferase).

RESULTS

We found a significant effect of CAG repeat length on AR protein levels per unit amount of DNA transfected (one‐way ANOVA, P = 0.02), indicating the need to express transactivation data per unit amount of AR protein. CAG17 AR had 40% more transactivation activity per unit amount of AR protein than CAG21 AR (P < 0.01).

CONCLUSIONS

Thus, an AR with a 17‐CAG repeat may mediate more efficacious growth stimulation of androgen‐dependent prostate epithelial cells, and thereby increase the risk that prostate cancer cells develop more efficiently into a clinically significant cancer. © 2003 Wiley‐Liss, Inc.
Chiral response of Oryzeae and Paniceae plants in α‐methylbenzyl‐3‐p‐tolyl urea agar medium
Authors: Omokawa Hiroyoshi , Murata Hiroshi , Kobayashi Shoko
Published: December 2003

The results presented here support the hypothesis that plants of the tribe Oryzeae respond enantioselectively and homogeneously to optically active 1‐α‐methylbenzyl‐3‐p‐tolylurea (MBTU) in root growth inhibition, in contrast to Echinochloa species. The Oryzeae plants tested in this study belong to different genera (Oryza, Leersia, Chikusichloa and Zizania), to different species (O sativa, O glaberrima, O alta, O coarctata, O latifolia, O minuta, O rufipogon), to various ecospecies of Oryza (japonica, indica, japonica × indica, javanica) and to different levels of evolution [cultivated rice (O sativa and O glaberrima) and ancestral wild rice species]. In spite of their different phylogenic status and diverse sensitivity, the root growth of all members of the genus Oryza was inhibited more by R‐MBTU than by S‐MBTU. Zizania palustris, Z latifolia, Leersia oryzoides and Chikusichloa aquatica belonging to the tribe Oryzeae exhibited similar chiral recognition to the Oryza plants, suggesting that Oryzeae have a common chiral recognition mechanism in their response to optically active MBTUs. In contrast, Echinochloa plants (E crus‐galli (L) Beauv var crus‐galli and E colonum (L) Link), belonging into subfamily Panicoideae tribe Paniceae, responded in a different way, where their root growth was more sensitive to S‐MBTU than to the antipodal R‐MBTU. A reverse chiral response between the tribe Oryzeae and the genus Echinochloa was clearly indicated in this study. This diverse response may be relevant to Gramineae classification. Copyright © 2003 Society of Chemical Industry
Distribution and persistence of emamectin benzoate at efficacious concentrations in pine tissues after injection of a liquid formulation
Authors: Takai Kazuya , Suzuki Toshio , Kawazu Kazuyoshi
Published: December 2003

In an earlier paper the authors reported the creation of a novel emamectin benzoate 40 g litre−1 liquid formulation (Shot Wan Liquid Formulation). The injection of this formulation exerted a preventative effect against the pine wilt disease caused by the pine wood nematode, Bursaphelenchus xylophilus (Steiner & Buhrer) Nickle, and this effect lasted for at least 3 years. The present study was carried out to show experimentally that the marked effect of this formulation was due to the presence and persistence in pine tissues of sufficient amounts of emamectin benzoate to inhibit nematode propagation. A cleanup procedure prior to quantitative analysis of emamectin benzoate by fluorescence HPLC was devised. The presence of the compound in concentrations sufficient to inhibit nematode propagation in the shoots of current growth and its persistence for 3 years explained the marked preventative effect. Non‐distribution of emamectin benzoate in some parts of the lower trunk suggested that the formulation should be injected at several points for large trees in order to distribute the compound uniformly to lower branches. Copyright © 2003 Society of Chemical Industry
Herbicide safety relative to common targets in plants and mammals
Authors: Shaner Dale L
Published: December 2003

Most modern herbicides have low mammalian toxicity. One of the reasons for this safety is that the target site for the herbicides is not often present in mammals. There are approximately 20 mechanisms of action that have been elucidated for herbicides. Of these, some do share common target sites with mammals. The mechanisms include formation of free radicals, protoporphyrinogen oxidase (PROTOX), glutamine synthetase (GS) and 4‐hydroxyphenylpyruvate dioxygenase (HPPD). PROTOX, HPPD and GS inhibitors have been shown to inhibit these enzymes in both plants and mammals and there are measurable effects in mammalian systems. However, the consequences of inhibiting a common target site in plants can be quite different than in animals. What may be a lethal event in plants, eg inhibition of HPPD, can have a beneficial effect in mammals, eg treatment for tyrosinemia type I. These chemicals also have low mammalian toxicity due to rapid metabolism and/or excretion of the herbicide from mammalian systems. Published in 2003 for SCI by John Wiley & Sons, Ltd.
Cross‐resistance pattern and alternative herbicides for Cyperus difformis resistant to sulfonylurea herbicides in Korea
Authors: Kuk Yong In , Kim Kyung Hyun , Kwon Oh Do , Lee Do Jin , Burgos Nilda R , Jung Sunyo , Guh Ja Ock
Published: December 2003

A Cyperus difformis L accession from Chonnam province, Korea was tested for resistance to the sulfonylurea herbicide, imazosulfuron. The accession was confirmed to be resistant (R) and was cross‐resistant to other sulfonylurea herbicides, bensulfuron‐methyl, cyclosulfamuron and pyrazosulfuron‐ethyl, the pyrimidinyl thiobenzoate herbicide, bispyribac‐sodium, and the imidazolinone herbicide imazapyr, but not to imazaquin. Multiple resistance was tested using twelve herbicides with target sites other than acetolactate synthase (ALS). The R biotype could be controlled by other herbicides with different modes of action such as butachlor, carfentrazone‐ethyl, clomeprop, dithiopyr, esprocarb, mefenacet, oxadiazon, pretilachlor, pyrazolate and thiobencarb, applied to soil at recommended rates. Several sulfonylurea herbicide‐based mixtures can control both the R and S biotypes of C difformis, except sulfonylurea plus dimepiperate, molinate or pyriftalid, and pyrazolate plus butachlor. Although mixtures of sulfonylurea herbicides might be more effective, they should be avoided and used only in special cases. In terms of in vitro ALS activity, the R biotype was 1139‐, 3583‐, 1482‐, 416‐, 5‐ and 9‐fold more resistant to bensulfuron‐methyl, cyclosulfamuron, imazosulfuron, pyrazosulfuron‐ethyl, bispyribac‐sodium and imazapyr, respectively, than the S biotype. The in vivo ALS activity of the R biotype was also less affected by the sulfonylurea herbicides, imazosulfuron and pyrazosulfuron‐ethyl, than the S biotype. Results of in vitro and in vivo ALS assays indicated that the resistance mechanism of C difformis to ALS inhibitor herbicides was primarily due to an alteration in the target enzyme, ALS. Greenhouse experiments showed delayed flowering and reduced seed production of the R biotype, which could possibly result in reduced fitness. This unusual observation needs to be confirmed in field situations. Copyright © 2003 Society of Chemical Industry
The discovery of pyridalyl: a novel insecticidal agent for controlling lepidopterous pests
Authors: Sakamoto Noriyasu , Saito Shigeru , Hirose Taro , Suzuki Masaya , Matsuo Sanshiro , Izumi Keiichi , Nagatomi Toshio , Ikegami Hiroshi , Umeda Kimitoshi , Tsushima Kazunori , Matsuo Noritada
Published: December 2003

Synthesis of analogues of two compounds with known insecticidal activity, both of which contain a 3,3‐dichloro‐2‐propenyloxy group, produced 2‐(trifluoromethyl)‐4‐phenoxyphenyl 3,3‐dichloro‐2‐propenyl ether, which had weak activity against lepidopterous larvae. Structural modifications around this lead compound led to the development of pyridalyl [Pleo®, S‐1812; 2,6‐dichloro‐4‐(3,3‐dichloroallyloxy)phenyl 3‐[5‐(trifluoromethyl)‐2‐pyridyloxy]propyl ether], which belongs to a new class of insecticides. Pyridalyl gives very good control of various lepidopterous and thysanopterous pests on cotton and vegetables, without phytotoxicity. It controls populations of Heliothis virescens F and Plutella xylostella (L) which are resistant to various currently used insecticides. It also produces unique insecticidal symptoms, so it may have a different mode of action from other existing insecticides. Pyridalyl is also less harmful than existing insecticides to various beneficial arthropods, so it should provide an important tool in IPM and insecticidal management programmes for the control of lepidopterous and thysanopterous pests. The first market introduction is expected in Japan and some Asian countries in the years between 2004 and 2005. Copyright © 2003 Society of Chemical Industry
Use of PRZM‐3 to validate a laboratory to field degradation conceptual model
Authors: Jackson Scott H
Published: December 2003

The test substance, boscalid, was applied at two field sites, but, depending on how kinetic calculations were performed, the time required for 50% of the initial compound concentration to dissipate (half‐life) ranged from 27 to 200 days. Laboratory aerobic soil studies indicated that the DT50 for the compound was about 108 days, and since compound dissipation rates are typically shorter in the field than those observed in the laboratory, confidence in the field half‐life calculations was questioned. Researchers have asked whether exposure models might be useful for relating laboratory to field behavior, especially when results are difficult to reconcile between the two systems. In order to determine how realistic field dissipation‐time kinetic calculations were, a 60‐day DT50 (some masked data), 150‐day DT50 and a 196‐day rate constant (t1/2) kinetic result were entered into the Pesticide Root Zone Model (PRZM‐3) for a California site. A 27‐day DT50, and a 200 day t1/2 kinetic result were also entered into the model for a Florida site. Results indicate that using the shortest DT50 solution in PRZM‐3 provided the best fit to actual field data. Results from this study suggest that PRZM‐3 can be used successfully to address uncertainty between a laboratory conceptual understanding of a compound's behavior and the actual behavior observed in the field. Copyright © 2004 Society of Chemical Industry
Detection of immune complexes by matrix‐assisted laser desorption/ionization mass spectrometry
Authors: Schlosser Gitta , Pocsfalvi Gabriella , Malorni Antonio , Puerta Angel , de Frutos Mercedes , Vékey Károly
Published: December 2003

Matrix‐assisted laser desorption/ionization mass spectrometry (MALDI‐MS) was used to detect an immune complex formed between β‐lactoglobulin and polyclonal anti‐β‐lactoglobulin antibody in the gas phase. The most important experimental parameters to detect such a specific antibody–antigen complex by MALDI were the use of solutions at near‐neutral pH and of sinapinic acid matrix prepared by the dried‐droplet method. Under such conditions, predominantly one but also two molecules of antigen protein were complexed by the antibody. Specific formation of the antibody–antigen complex was confirmed by performing competitive reactions. Addition of antibody to a 1:1 mixture of β‐lactoglobulin and one control protein resulted not only in the appearance of the expected antibody–antigen complex, but also in a strong decrease in the free β‐lactoglobulin signal, while the abundance of the control protein was not influenced. Copyright © 2003 John Wiley & Sons, Ltd.
Dynamic calibration and dissolved gas analysis using membrane inlet mass spectrometry for the quantification of cell respiration
Authors: Yang Tae Hoon , Wittmann Christoph , Heinzle Elmar
Published: December 2003

A membrane inlet mass spectrometer connected to a miniaturized reactor was applied for dynamic dissolved gas analysis. Cell samples were taken from 7 mL shake flask cultures of Corynebacterium glutamicum ATCC 13032, and transferred to the 12 mL miniaturized reactor. There, oxygen uptake and carbon dioxide and its mass isotopomer production rates were determined using a new experimental procedure and applying nonlinear model equations. A novel dynamic method for the calibration of the membrane inlet mass spectrometer using first‐order dynamics was developed. To derive total dissolved concentration of all carbon dioxide species (CT) from dissolved carbon dioxide concentration ([CO2]aq), the ratio of CT to [CO2]aq was determined by nonlinear parameter estimation, whereas the mass transfer coefficient of CO2 was determined by the Wilke–Chang correlation. Subsequently, the suitability of the model equations for respiration measurements was examined using residual analysis and the Jarque–Bera hypothesis test. The resulting residuals were found to be random with normal distribution, which proved the adequacy of the application of the model for cell respiration analysis. Hence, dynamic changes in respiration activities could be accurately analyzed using membrane inlet mass spectrometry with the novel calibration method. Copyright © 2003 John Wiley & Sons, Ltd.
Enzymatic strategies for the characterization of nucleic acids by electrospray ionization mass spectrometry
Authors: Null Allison P. , Benson Linda M. , Muddiman David C.
Published: December 2003

Electrospray ionization mass spectrometry (ESI‐MS) is a powerful technique used for the identification and characterization of DNA polymorphisms. Continual improvement in instrument design assures high mass measurement accuracy, sensitivity, and resolving power. This work describes an eclectic array of enzymatic strategies we have invoked in order to detect single‐nucleotide polymorphisms by ESI‐MS, although other applications may be envisioned. One strategy combines the use of two enzymes, exonuclease III and lambda exonuclease, to provide a ladder of single‐stranded DNA fragments for straightforward sequence identification by mass spectrometry. A second strategy combines restriction enzymes to screen for polymorphisms present within specific amplicons. Finally, we describe the use of stable‐isotope‐labeled nucleotides for the determination of length and base composition of a PCR product. Copyright © 2003 John Wiley & Sons, Ltd.
Fourier transform ion cyclotron resonance mass spectrometry using atmospheric pressure photoionization for high‐resolution analyses of corticosteroids
Authors: Greig Michael J. , Bolaños Ben , Quenzer Terri , Bylund Jessica M. R.
Published: December 2003

Fourier transform ion cyclotron resonance mass spectrometry (FTICRMS) was coupled with atmospheric pressure photoionization (APPI) for the first time and used for the analysis of several corticosteroids.1 The analytes showed excellent response using APPI when compared with both electrospray ionization (ESI) and atmospheric pressure chemical ionization (APCI). APPI has the advantage of requiring less heat for desolvation, resulting in less thermal degradation of the analytes and higher signal‐to‐noise than APCI. In terms of ultimate sensitivity, APPI is more efficient than either ESI or APCI for the analysis of corticosteroids. With some compounds, the high‐resolution capability of FTICRMS was necessary to obtain an accurate mass due to contributions of the M+. 13C isotope in the [M+H]+ ion peak. Copyright © 2003 John Wiley & Sons, Ltd.
Electrospray mass spectrometry in the differentiation of some isomeric trimethylfurocoumarins
Authors: Basso Elisa , Chilin Adriana , Guiotto Adriano , Traldi Pietro
Published: December 2003

Electrospray mass spectrometry (ES‐MS) was successfully employed for the structural differentiation of six isomeric trimethylfurocoumarins of possible pharmaceutical interest. Two different approaches were employed. The first was based on MSn experiments of MH+ ions. Although the product ion spectra of MH+ of the isomers are very similar, the MS3 spectra of the collisionally generated [MHCO]+ ions show some characteristic differences. The second approach was based on complexation of the molecules with Li+, Na+ and K+ using ESI‐MS of sample solutions containing alkali ions in a 100:1 molar ratio with respect to the analyte. Significant differences were observed in complex production yields, and these were related to the dimension of the alkali ion and to the steric availability of chelating groups in the different isomers. Copyright © 2003 John Wiley & Sons, Ltd.
Characteristic fragmentation of bacteriohopanepolyols during atmospheric pressure chemical ionisation liquid chromatography/ion trap mass spectrometry
Authors: Talbot Helen M. , Summons Roger , Jahnke Linda , Farrimond Paul
Published: December 2003

Bacteriohopanepolyols (BHPs) fragment via characteristic pathways during atmospheric pressure chemical ionisation liquid chromatography/ion trap mass spectrometry (APCI‐LC/MSn). Comparison of the MS2 spectra of bacteriohopane‐32,33,34,35‐tetrol (BHT) and 2β‐methylbacteriohopane‐32,33,34,35‐tetrol has confirmed the previously proposed ring‐C cleavage occurring between C‐9 and 11 and C‐8 and 14. This fragmentation, diagnostic of all hopanoids, also occurs in BHPs containing an amino group (‐NH2) at C‐35 although the higher relative stability of the ion limits this fragmentation to a minor process after protonation of the basic nitrogen function. Studies of a number of cell cultures including a prochlorophyte (Prochlorothrix hollandica) and a cyanobacterium (Chlorogloeopsis LA) demonstrate the power of this technique to detect composite BHPs with a complex biological functionality at C‐35. We also report the first observation of intact pentafunctionalised bacteriohopanepolyols using this method. Copyright © 2003 John Wiley & Sons, Ltd.
The use of nonpolar matrices for matrix‐assisted laser desorption/ionization mass spectrometric analysis of high boiling crude oil fractions
Authors: Robins Chad , Limbach Patrick A.
Published: December 2003

Matrix‐assisted laser desorption/ionization time‐of‐flight mass spectrometry (MALDI‐TOFMS) with nonpolar matrices has been investigated for its applicability to the characterization of atmospheric resid crude oil fractions. The data obtained by use of nonpolar matrices was compared with that from polar matrices as well as from direct LDI‐MS and field ionization mass spectrometry. Nonpolar matrices, such as anthracene or 9‐cyanoanthracene, yield only a single radical molecular cation upon LDI. Thus, no interfering matrix‐related ions are present during the MALDI‐TOFMS analysis of the crude oil sample. Nonpolar matrices yield molecular mass distributions from linear mode MALDI‐TOFMS that are comparable to distributions found with LDI‐MS. An advantage of nonpolar matrices is the increased production of analyte ions, which allows reflectron mode MALDI‐TOFMS to be performed. Nonpolar matrices are also shown to be less sensitive to solvent and sample preparation conditions than conventional polar matrices. These results suggest that nonpolar matrices may be favorable alternatives to more traditional polar or acidic matrices commonly used in the MALDI mass spectral characterization of crude oil related samples. Copyright © 2003 John Wiley & Sons, Ltd.
Probabilistic approach to developing nephropathy in diabetic patients with retinopathy
Authors: Ballone Enzo , Colagrande Vittorio , Di Nicola Marta , Di Mascio Rocco , Di Mascio Claudio , Capani Fabio
Published: December 2003

It is well known that diabetes is a risk factor for many complications including diabetic retinopathy and nephropathy. An interesting question is whether a diabetic patient who has developed a retinopathy develops a nephropathy sooner. We approached this problem by calculating the conditional probability that a diabetic patient will develop a second complication, given that they had already developed the first complication. We also propose the application of Bayes' formula to estimate the probability of developing the second complication, given that the first complication had developed previously. We compared these two methods by applying them to analyse 5473 patients with type 2 diabetes. The results of our experience are described. Copyright © 2003 John Wiley & Sons, Ltd.
Comparison of case‐cohort estimators based on data on premature death of adult adoptees
Authors: Petersen Liselotte , Sørensen Thorkild I. A. , Andersen Per Kragh
Published: December 2003

A case‐cohort sample of adoptees was collected to investigate genetic and environmental influences on premature death, which motivated us to supplement existing simulation results to explore the performance of various estimators proposed for case‐cohort samples of survival data. We studied six regression coefficients estimators, which differ with regard to the weighting scheme used in a pseudo‐likelihood function, and two different estimators of their variances. Compared to earlier simulation studies, we changed the following conditions: type of explanatory variable, the distribution of lifetimes, and the percentage of deaths in the full cohort. The latter condition affected the performance of the estimated variances of the regression coefficients, where we found a systematic bias of the estimator, proposed by Self and Prentice, dependent on the percentages of deaths. This dependence of percentages of death was different for different sizes of case‐cohort studies. A robust variance estimator showed a better overall performance. The estimators of regression coefficients compared did not differ much, the estimators proposed by Kalbfleisch and Lawless and by Prentice performing very well. Results of the case‐cohort data of adoptees were not in conflict with earlier findings of a moderate genetic influence on premature death in adulthood. Copyright © 2003 John Wiley & Sons, Ltd.
Proper metrics for clinical trials: transformations and other procedures to remove non‐normality effects
Authors: Lachenbruch Peter A.
Published: December 2003

A simulation study was performed to study the effects of non‐normality and to examine procedures to ameliorate possible loss of power when data are incorrectly assumed to be normally distributed. It was found that only distributions with high asymmetry or heavy tails seriously affect the t‐test. The Box–Cox likelihood ratio test appears to have some advantages over the others, but this must be offset by the greater complexity in making the results understandable to non‐statisticians. The variability in outcomes with the different procedures demonstrates the importance of specifying such proceduresa priori. Published in 2003 by John Wiley & Sons, Ltd.
The analysis of the influence of birth order and other factors in multiple birth data
Authors: Davidov Ori , Murad Havi , Lusky Ayala , S Shinwell Eric , Reichman Brian , Freedman Laurence
Published: December 2003

We compare three methods which can be used to analyse theinfluence of birth order and other factors on health outcomes inmultiple birth data. We consider marginal models based ongeneralized estimating equations (GEE) and two kinds ofconditional models; conditional logistic regression (CLR) andmixed effects models (MEM). Although the models may be writtensimilarly, there are differences in both the interpretation andthe numerical values assigned to the parameters. Our mainconclusion is that GEE and MEM are preferable to CLR since theyprovide more flexibility in dealing with missing values andcovariates. The choice between GEE and MEM is less obvious anddepends on the data, the parameter of interest and statisticalpower. Copyright © 2003 John Wiley & Sons, Ltd.
Comparison of JavaServer Pages and XSLT: a software engineering perspective
Authors: Dunkel Jürgen , Bruns Ralf , Holitschke Andreas
Published: December 2003

Professional Web applications present their content and services by means of dynamically generated Web pages to the user—normally HTML pages. Basically, there are two different technologies available for dynamic Web page generation—JavaServer Pages and XML/XSLT. In this paper the alternative technologies are compared from a software engineering perspective.

The basic concepts of JavaServer Pages and XML/XSLT are briefly explained with respect to Web page generation. A universal software architecture of the server side presentation tier is introduced and it is shown how both technologies fit into the universal architecture. Its fundamental idea is the clear separation of concerns according to the well‐established model‐view‐controller design pattern. The proposed architecture has proven its applicability in several enterprise applications. The main part of the paper deals with the comparison of JavaServer Pages and XML/XSLT. Quality criteria well‐established in software engineering practice are discussed with respect to JavaServer Pages and XML/XSLT, e.g. maintainability, extensibility, reusability, efficiency, portability, integration of methods and tools. The main emphasis is laid on the support of the model‐view‐controller pattern, since it is the most established design principle for user interface design. Copyright © 2003 John Wiley & Sons, Ltd.
An extensible probe architecture for network protocol performance measurement
Authors: Watson David , Malan G. Robert , Jahanian Farnam
Published: December 2003

This paper describes the architecture, implementation, and application of Windmill, a passive network protocol performance measurement tool. Windmill enables experimenters to measure a broad range of protocol performance metrics both by reconstructing application‐level network protocols and by exposing the underlying protocol layers' events. Windmill is split into three functional components: a dynamically compiled Windmill Protocol Filter (WPF), a set of abstract protocol modules, and an extensible experiment engine. To demonstrate Windmill's utility, we present the results from several experiments. The first set of experiments validates a possible cause for the correlation between Internet routing instability and network bandwidth usage. The second set of experiments highlights Windmill's ability to act as a driver for a complementary active Internet measurement infrastructure, its ability to perform online data reduction, and the non‐intrusive measurement of a closed system. Copyright © 2003 John Wiley & Sons, Ltd.
A Logic for Schema-Based Program Development
Authors: Henson Martin C. , Reeves Steve
Published: December 2003

We show how a theory of specification refinement and program development can be constructed as a conservative extension of our existing logic for Z. The resulting system can be set up as a development method for a Z-like specification language, or as a generalisation of a refinement calculus (with a novel semantics). In addition to the technical development we illustrate how the theory can be used in practice.
Deep Semantic Links of TCSP and Object-Z: TCOZ Approach
Authors: Mahony Brendan , Dong Jin Song
Published: December 2003

Formal methods can be used in effective combination only if the semantic links between individual methods are clearly established. This paper discusses the semantic design of TCOZ, a language blended from Object-Z and TCSP. The semantic model adopted is the infinite timed failures model of TCSP, extended to include initial state and update events for modelling operations on internal state. An infinite trace model has been used so as to ensure proper account is taken of the potentially unbounded non-determinism allowed by Z schemas.
Architectural Specifications in CASL
Authors: Bidoit Michel , Sannella Donald , Tarlecki Andrzej
Published: December 2003

One of the most novel features of C

ASL

, the Common Algebraic Specification Language, is the provision of so-called
architectural specifications
for describing the modular structure of software systems. A brief discussion of refinement of C

ASL

specifications provides the setting for a presentation of the rationale behind architectural specifications. This is followed by some details of the features provided in C

ASL

for architectural specifications, hints concerning their semantics, and simple results justifying their usefulness in the development process.
Institution Morphisms
Authors: Goguen Joseph , Roşu Grigore
Published: December 2003

Institutions formalise the intuitive notion of logical system, including syntax, semantics, and the relation of satisfaction between them. Our exposition emphasises the natural way that institutions can support deduction on sentences, and inclusions of signatures, theories, etc.; it also introduces terminology to clearly distinguish several levels of generality of the institution concept. A surprising number of different notions of morphism have been suggested for forming categories with institutions as objects, and an amazing variety of names have been proposed for them. One goal of this paper is to suggest a terminology that is uniform and informative to replace the current chaotic nomenclature; another goal is to investigate the properties and interrelations of these notions in a systematic way. Following brief expositions of indexed categories, diagram categories, twisted relations and Kan extensions, we demonstrate and then exploit the duality between institution morphisms in the original sense of Goguen and Burstall, and the ‘plain maps’ of Meseguer, obtaining simple uniform proofs of completeness and cocompleteness for both resulting categories. Because of this duality, we prefer the name ‘comorphism’ over ‘plain map’; moreover, we argue that morphisms are more natural than comorphisms in many cases. We also consider ‘theoroidal’ morphisms and comorphisms, which generalise signatures to theories, based on a theoroidal institution construction, finding that the ‘maps’ of Meseguer are theoroidal comorphisms, while theoroidal morphisms are a new concept. We introduce ‘forward’ and ‘semi-natural’ morphisms, and develop some of their properties. Appendices discuss institutions for partial algebra, a variant of order sorted algebra, two versions of hidden algebra, and a generalisation of universal algebra; these illustrate various points in the main text. A final appendix makes explicit a greater generality for the institution concept, clarifies certain details and proves some results that lift institution theory to this level.
Variations on Algebra: Monadicity and Generalisations of Equational Therories
Authors: Robinson Edmund
Published: December 2003

This is a largely tutorial paper about the categorical notion of monad and the ways in which monads on different categories correspond to variations on the standard notion of algebraic theory.
A New Approach to Abstract Syntax with Variable Binding
Authors: Gabbay Murdoch J. , Pitts Andrew M.
Published: December 2003

The permutation model of set theory with atoms (FM-sets), devised by Fraenkel and Mostowski in the 1930s, supports notions of ‘name-abstraction’ and ‘fresh name’ that provide a new way to represent, compute with, and reason about the syntax of formal systems involving variable-binding operations. Inductively defined FM-sets involving the name-abstraction set former (together with Cartesian product and disjoint union) can correctly encode syntax modulo renaming of bound variables. In this way, the standard theory of algebraic data types can be extended to encompass signatures involving binding operators. In particular, there is an associated notion of structural recursion for defining syntax-manipulating functions (such as capture avoiding substitution, set of free variables, etc.) and a notion of proof by structural induction, both of which remain pleasingly close to informal practice in computer science.