bluuebunny/crossref_metadata_2025 huggingface dataset:
Thermolysis of 3‐alkyl‐3‐methyl‐1,2‐dioxetanes: Activation parameters and chemiexcitation yields
Authors: Baumstark Alfons L. , Anderson Sean L. , Sapp Chariety J. , Vasquez Pedro C.
Published: August 2002

3‐Methyl‐3‐(3‐pentyl)‐1,2‐dioxetane 1 and 3‐methyl‐3‐(2,2‐dimethyl‐1‐propyl)‐1,2‐dioxetane 2 were synthesized in low yield by the α‐bromohydroperoxide method. The activation parameters were determined by the chemiluminescence method (for 1 ΔH‡ = 25.0 ± 0.3 kcal/mol, ΔS‡ = −1.0 entropy unit (e.u.), ΔG‡ = 25.3 kcal/mol, k1 (60°C) = 4.6 × 10−4s−1; for 2 ΔH‡ = 24.2 ± 0.2 kcal/mol, ΔS‡ = −2.0 e.u., ΔG‡ = 24.9 kcal/mol, k1 (60°C) = 9.2 × 10−4s−1. Thermolysis of 1–2 produced excited carbonyl fragments (direct production of high yields of triplets relative to excited singlets) (chemiexcitation yields for 1: ϕT = 0.02, ϕ ≤ 0.0005; for 2: ϕT = 0.02, ϕS ≤ 0.0004). The results are discussed in relation to a diradical‐like mechanism. © 2001 John Wiley & Sons, Inc. Heteroatom Chem 12:459–462, 2001
Synthesis of derivatives of 1,3,2‐diazaphospholidin‐4‐ones and the corresponding 2‐sulfides
Authors: He Liangnian , Luo Yanping , Ding Mingwu , Lu Aihong , Liu Xiaopeng , Wu Tianjie , Cai Fei
Published: August 2002

Aromatic‐substituted derivatives of 1,3,2‐diazaphospholidin‐4‐ones 2a–g were readily prepared from 1,3‐diaryl glycinamides 1 by the reaction with hexaethylphosphoric triamide. Their chemical transformation was selectively effected with different thionation reagents to afford thionated products at the phosphorus atom to give 3a–g and at the carbonyl group to give 4a. An oxidation reaction at phosphorus to produce 5a was effected with 10% hydrogen peroxide. Preliminary bioassays revealed that some of the title compounds, 2a–g and 3a–g possess selective herbicidal activity against rape. © 2001 John Wiley & Sons, Inc. Heteroatom Chem 12:497–500, 2001
Searching for a better willingness to pay elicitation method in rural Nigeria: the binary question with follow‐up method versus the bidding game technique
Authors: Onwujekwe Obinna
Published: August 2002

Objectives: To compare the theoretical validity and predictive validity of the binary with follow‐up questions technique and the bidding game, using hypothetical and actual WTP for insecticide‐treated nets (ITNs) in Nigeria.

Methods: Each elicitation method was applied in one of two rural communities in Enugu state, Nigeria. A pre‐tested interviewer‐administered questionnaire was administered to household heads or representatives of households. WTP was elicited in each after presenting the scenario and showing a sample of the ITNs to the respondents. Then, within an interval of 1–2 months, the nets were sold to the respondents to compare hypothetical and actual WTP.

Findings: Consistent slightly higher mean and median WTP amounts were elicited from Mbano where the bidding game was used. The WTP technique was able to predict WTP responses correctly in 75% and 85% of cases in Orba and Mbano, respectively. Chi‐square analysis did not show any statistical difference in values from both communities (p>0.05).

Conclusion: Though the two techniques yielded similar results, the thrust should be the development of a WTP elicitation method that best mimics the bargaining process in normal market situations in rural Nigeria. Such an indigenous technique will help improve the predictive validity of the contingent valuation method. Copyright © 2001 John Wiley & Sons, Ltd.
Synchronous benign and malignant salivary gland tumors in ipsilateral glands: A report of two cases and a review of literature
Authors: Curry Jonathan L. , Petruzzelli Guy J. , McClatchey Kenneth D. , Lingen Mark W.
Published: August 2002

Background

Ipsilateral salivary gland tumors of different histologic types are rare and make up less than 0.3% of all salivary gland neoplasms. Only nine cases of synchronous benign and malignant ipsilateral parotid gland tumors have been described in the literature.

Methods

Two additional cases of synchronous benign and malignant neoplasms in the parotid gland are reported and discussed with a review of literature.

Results

Our first case describes a pleomorphic adenoma and a salivary duct carcinoma, an entity not previously reported in the literature. The second case documents the most common benign and malignant ipsilateral parotid gland neoplasm reported in this case series, a Warthin's tumor and a mucoepidermoid carcinoma.

Conclusions

Synchronous salivary gland tumors exhibiting both benign and malignant components are uncommonly observed, with only nine cases published to date. We describe two additional cases of a synchronous benign and malignant ipsilateral parotid gland tumor. © 2002 Wiley Periodicals, Inc. Head Neck 24: 301–306, 2002; DOI 10.1002/hed.10048
Pilot trial of concomitant chemotherapy with paclitaxel and split‐course radiotherapy for very advanced squamous cell carcinoma of head and neck
Authors: Feher Olavo , Martins Sandro J. , Lima Candice A. , Salvajoli João V. , Simpson Andrew J. , Kowalski Luiz P.
Published: August 2002

Purpose

The combination of chemotherapy and irradiation is considered the standard of care for the treatment of advanced squamous cell carcinoma of head and neck (SCCHN). Paclitaxel has shown a single‐agent activity in SCCHN. Besides, this drug is a promising radiosensitizer for some human solid tumors. This is a phase II trial to evaluate the feasibility, efficacy, and toxicity of paclitaxel administered concurrently with split‐course radiotherapy in advanced unresectable SCCHN.

Methods and Materials

Thirty‐one patients with advanced SCCHN were enrolled in this trial. Radiotherapy consisted of 66 to 70 Gy delivered over 8 to 10 weeks to the primary tumor and lymphatic drainage, with a fractionation scheme of 1.8 to 2 Gy/field/d. After the initial five patients were treated, a 1‐week treatment break was introduced. Paclitaxel was administered weekly in a 1‐hour intravenous infusion at a projected dosage of 45 mg/m2/wk.

Results

The complete and partial response rates, based on a 4‐week postradiation evaluation were 43.3% and 40%, respectively, with an overall response rate of 83.3%. Median survival was 49.4 weeks, and 1‐year survival was 48%. Freedom from local progression was 65.6% at 1 year. Thirty‐six percent and 20% of the patients are alive and disease free at 1 and 2 years, respectively. Grade 3/4 of acute toxicity consisted mostly of mucositis, cutaneous reaction, and weight loss.

Conclusions

Paclitaxel concurrent with radiotherapy seems to be active in squamous cell carcinoma of the head and neck. In the regimen selected for this trial, toxicity was significant and led to a prolongation of treatment time. © 2002 Wiley Periodicals, Inc. Head Neck 24: 228–235, 2002; DOI 10.1002/hed.10049
Preoperative magnetic resonance angiography in fibular‐free flap reconstruction of head and neck defects
Authors: Lorenz Robert R. , Esclamado Ramon
Published: August 2002

Background

Conventional angiography has been recommended for imaging of the leg prior to fibular‐free flap harvest. Magnetic resonance angiography (MRA) offers a similar level of accuracy at no risk to the patient and at a lower cost.

Methods

Thirty‐two patients who were considered for fibular‐free flap were retrospectively reviewed. Preoperative MRA of the lower extremities was performed on all patients and used to evaluate vessel patency. The decision of free flap donor site was based upon MRA findings.

Results

The choice of side harvested was changed in four (12.5%) patients and the fibula was excluded as a donor site in three patients (9%). Flap design was altered in one patient found to have abnormally short peroneal arteries. The usual correlation between palpable distal pulses and proximal patent arteries was found to be unreliable. All 29 patients underwent successful free flap reconstruction with no ischemic complications.

Conclusions

Preoperative MRA is useful when choosing the side of fibular harvesting and in excluding patients from the fibula as a donor site. We feel that the cost of obtaining preoperative imaging is outweighed by avoiding potential ischemic complications and additional operating room time with no risk to the patient's health. © 2001 John Wiley & Sons, Inc. Head Neck 23: 844–850, 2001.
Ergonomics considerations and management action in the implementation of industrial robots
Authors: Das Biman
Published: August 2002

To obtain maximum benefit from the implementation of industrial robots, it is necessary to identify specific ergonomics problems and provide answers to such problems. Special features of a typical industrial robot are described. Specific ergonomics problems are identified and discussed: sociopsychological factors, systems safety design, communications, training, and workplace design. For the successful implementation of industrial robots, management should take timely action with regard to advanced planning procedures, user involvement plans, communication channels, company labor policies, and continuous training programs. The technological change from conventional to advanced manufacturing, such as industrial robots, must be jointly supported by all levels of management and workers. © 2001 John Wiley & Sons, Inc.
Under what conditions is recognition spared relative to recall after selective hippocampal damage in humans?
Authors: Holdstock J.S. , Mayes A.R. , Roberts N. , Cezayirli E. , Isaac C.L. , O'Reilly R.C. , Norman K.A.
Published: August 2002

The claim that recognition memory is spared relative to recall after focal hippocampal damage has been disputed in the literature. We examined this claim by investigating object and object–location recall and recognition memory in a patient, YR, who has adult‐onset selective hippocampal damage. Our aim was to identify the conditions under which recognition was spared relative to recall in this patient. She showed unimpaired forced‐choice object recognition but clearly impaired recall, even when her control subjects found the object recognition task to be numerically harder than the object recall task. However, on two other recognition tests, YR's performance was not relatively spared. First, she was clearly impaired at an equivalently difficult yes/no object recognition task, but only when targets and foils were very similar. Second, YR was clearly impaired at forced‐choice recognition of object–location associations. This impairment was also unrelated to difficulty because this task was no more difficult than the forced‐choice object recognition task for control subjects. The clear impairment of yes/no, but not of forced‐choice, object recognition after focal hippocampal damage, when targets and foils are very similar, is predicted by the neural network‐based Complementary Learning Systems model of recognition. This model postulates that recognition is mediated by hippocampally dependent recollection and cortically dependent familiarity; thus hippocampal damage should not impair item familiarity. The model postulates that familiarity is ineffective when very similar targets and foils are shown one at a time and subjects have to identify which items are old (yes/no recognition). In contrast, familiarity is effective in discriminating which of similar targets and foils, seen together, is old (forced‐choice recognition). Independent evidence from the remember/know procedure also indicates that YR's familiarity is normal. The Complementary Learning Systems model can also accommodate the clear impairment of forced‐choice object–location recognition memory if it incorporates the view that the most complete convergence of spatial and object information, represented in different cortical regions, occurs in the hippocampus. Hippocampus 2002;12:341–351. © 2002 Wiley‐Liss, Inc.
PET imaging of ischemic neuronal death in the hippocampus of living monkeys
Authors: Zhao Liang , Yamashima Tetsumori , Wang Xiang‐Di , Tonchev Anton B. , Yamashita Junkoh , Kakiuchi Takeharu , Nishiyama Shingo , Kuhara Shigehide , Takahashi Kazuhiro , Tsukada Hideo
Published: August 2002

The aim of the present study was to visualize postischemic hippocampal neuronal death in the living monkey brain, using a high‐resolution positron emission tomography (PET) and novel radioligands. In preceding papers, we reported on postischemic hippocampal neuronal death in a model of Japanese monkeys (Macaca fuscata) undergoing a 20‐min complete whole‐brain ischemia. Using the same model here, we investigated the in vivo bindings of two radiotracers, [11C]Ro15‐4513 (a type II benzodiazepine receptor ligand) and [11C](+)3‐MPB (a muscarinic cholinergic receptor ligand), in the hippocampus on day 7 after ischemia, as compared to the normal hippocampus. A significant decrease in the in vivo binding of [11C]Ro15‐4513 and [11C](+)3‐MPB was observed in the postischemic monkey hippocampus on day 7 after ischemia compared to controls. Light and electron microscopic analyses of postischemic CA1 neurons showed typical features of coagulation necrosis, as associated with a marked reduction of postsynaptic densities and presynaptic vesicles. These results suggest that semiquantification of hippocampal neuronal death is possible in the living primate brain using PET, and that the same procedures can be applied for evaluating neuronal cell loss in patients with ischemic injuries and/or dementia. Hippocampus 2002;12:109–118. © 2002 Wiley‐Liss, Inc.
Recent research and development of combustion simulation
Authors: Aoki Hideyuki , Suzuki Akira , Hisaeda Yutaka , Suwa Yoshikazu , Nakagawa Tatsuji , Yaga Mitsuru , Shoji Masakazu , Miura Takatoshi
Published: August 2002

We present (1) gas fuel combustion rate expressions using the full kinetic reaction mechanism and the reduced mechanism, (2) a comparison of calculated results by Lagrangian and Eulerian methods on spray and solid particles, (3) the wall boundary treatment such as a wall function and low Reynolds number model, (4) a devolatilization reaction model of pulverized coal such as the FLASHCHAIN model, (5) k–ϵ turbulence model and LES approach on combustion flow field, (6) radiative heat transfer in combustion, (7) soot formation in the flame, (8) NOx formation mechanism, and (9) treatment on unburned particle fragmentation. Considering this overview of the above‐mentioned modeling, the future of combustion simulation is discussed. © 2001 Scripta Technica, Heat Trans Asian Res, 30(7): 581–613, 2001
Augmentation of boiling heat transfer from horizontal cylinder to liquid by movable particles
Authors: Iida Yoshihiro , Tsuyuki Toshikatsu , Mashima Takao , Takashima Takeo , Okuyama Kunito
Published: August 2002

This paper presents a series of experimental results on a passive augmentation technique of boiling heat transfer by supplying solid particles in liquid. A cylindrical heater 0.88 mm in diameter is placed in saturated water, in which a lot of mobile particles exist, and the nucleate and film boiling heat transfer characteristics are measured. Particle materials used were alumina, glass, and porous alumina, and the diameter ranged from 0.3 mm to 2.5 mm. Particles are fluidized by the occurrence of boiling without any additive power, and the heat transfer is augmented. The maximum augmentation ratio obtained in this experiment reaches about ten times the heat transfer coefficient obtained in liquid alone. The augmentation ratio is mainly affected by the particle material, diameter, and the height of the particle bed set at no boiling condition. The augmentation mechanism is discussed on the basis of the experimental results. © 2001 Scripta Technica, Heat Trans Asian Res, 31(1): 28–41, 2002
Equation of state for fluid mixtures based on the principle of corresponding states with a two‐fluid model: Application to fluid mixtures of water + ammonia
Authors: Suzuki Jun‐ichi , Uematsu Masahiko
Published: August 2002

We propose an equation of state for fluid mixtures of water + ammonia which is expressed in Helmholtz free energy as a function of temperature, molar volume, and mole fraction. IAPWS Formulation 1995 for water and the equation of state by Tillner‐Roth and colleagues for ammonia should be used for each pure component with the present equation. We applied the principle of corresponding states with a two‐fluid model to the present equation for fluid mixtures. On comparison with experimental data, the uncertainty in property calculations by the present equation was evaluated: within ±0.03 · x for bubble point curve, within ±0.04 · x for dew point curve, within ±0.02 · ρL for saturated liquid density, and within ±0.02 · ρ for PVTX properties. © 2002 Wiley Periodicals, Inc. Heat Trans Asian Res, 131(4): 320–330, 2002; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/htj.10023
Structure and void fraction in a liquid slug for gas–liquid two‐phase slug flow
Authors: Mori Koji , Miwa Megumi
Published: August 2002

The distribution of gas and liquid in a gas–liquid two‐phase slug flow was measured using semi‐supermultiple point‐electrode probes. Based on the measurements, the wake zone behind a gas slug and the low void‐fraction zone in a liquid slug were defined, and the void fractions of the two zones were determined. The data revealed that the void fraction of the wake zone increased with superficial gas velocity, yet was virtually independent of superficial liquid velocity. Nondimensional head was proposed as an informative characteristic of this system, accounting for the momentum change of the liquid in the wake zone. It was clarified that the nondimensional head was closely related to the void fraction of the wake zone. A good practical relationship was found between the nondimensional head and the lengths of a swelling liquid‐front zone and the wake zone. Furthermore, empirical correlations were proposed for the void fraction in the wake zone, the mean void fraction in the liquid slug, and the lengths of the swelling liquid‐front zone and the wake zone. © 2002 Wiley Periodicals, Inc. Heat Trans Asian Res, 31(4): 257–271, 2002; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/htj.10029
Sex differences in estimation of time intervals and in reaction time are removed by moderate but not high doses of caffeine in coffee
Authors: Botella Paloma , Bosch Francisco , Romero Francisco J. , Parra Andrés
Published: August 2002

Estimation of the passage of time in the seconds‐to‐minutes range and reaction time are strongly dependent on a hypothetical internal clock. Dopamine is the neurotransmitter most closely related to the rate of this clock. Caffeine, probably the most consumed drug in the world, leads to an augmentation of dopamine neurotransmission. In this study coffee, which reproduces the conditions under which caffeine is normally ingested, containing 3, 75, 150 or 300 mg of caffeine, was given to healthy male and female volunteers. A computerized time estimation and reaction time test was carried out 50 min after ingestion. Sex differences in placebo control subjects (who took decaffeinated coffee with 3 mg of caffeine), with females making more accurate estimates of time intervals than males and males showing shorter reaction times than females, were removed in subject taking doses of 75 and 150 mg of caffeine in the case of time estimation and 150 mg in the case of reaction time. The 300 mg dose induced overestimation of time in females and shortened the reaction time in males. There were no sex differences in the pharmacokinetics of caffeine, as measured in salivary concentration of caffeine using high‐performance liquid chromatography. Results indicating sex differences in time estimation or reaction time should not be generalized from the laboratory to real life without considering the fact that everyday coffee consumption may eliminate these differences. Copyright © 2001 John Wiley & Sons, Ltd.
Personality dimensions and psychopathological profiles of Ecstasy users
Authors: Dughiero Giuliana , Schifano Fabrizio , Forza Giovanni
Published: August 2002

Only limited information is available with respect to personality traits and the psychopathological characteristics of Ecstasy users. To shed some light on the issue, we compared a group of 43 Ecstasy consumers (made up of both ‘experimenters’, those who took ≤ 27.5 tablets in their lifetime, and ‘abusers’, those who took larger amounts of the drug) with a composite control group of 77 subjects (made up of drug‐free people, cannabis users and users of illicit drugs other than Ecstasy). Three instruments were used: the Questionnaire for the Assessment of the Use of Entactogenic Drugs (to assess modalities and characteristics of Ecstasy use); the Cloninger Tridimensional Personality Questionnaire (which measures harm avoidance, reward dependence and novelty seeking) and the SCL‐90 (which measures 10 different psychiatric variables). The Ecstasy consumer group subjects showed higher novelty seeking scores than the controls (p < 0.001), and Ecstasy experimenters showed lower harm avoidance scores than the abusers (p = 0.029), but values of both reward dependence and harm avoidance dimensions were associated with sex. On the SCL‐90, Ecstasy users showed higher scores than the controls on the obsession‐compulsion (p = 0.004), phobic anxiety (p = 0.037), psychoticism (p = 0.005) and sleep disturbances (p = 0.046) subscales. However, many of the SCL‐90 subscale results were associated with sex, and only the psychoticism values seemed to suggest a clinical condition. The main finding of this study is that high novelty seeking scores are characteristic of Ecstasy consumers: The propensity to look selectively for novelties could possibly act as a predisposing factor for Ecstasy abuse itself. Copyright © 2001 John Wiley & Sons, Ltd.
Seasonal characterization of microwave emissions from snow‐covered first‐year sea ice
Authors: Harouche Isabelle P.‐F. , Barber David G.
Published: August 2002

Brightness temperature TB data were collected with a surface‐based radiometer operating on both vertical and horizontal polarizations at frequencies of 19, 37, and 85 GHz. Both microwave emissions and thermophysical data were collected as part of the Collaborative–Interdisciplinary Cryospheric Experiment between 15 May and 25 June 2000, in the Canadian High Arctic. Each season was characterized by a running variance of the time series in the microwave emissions. The seasonal analysis was conducted through observed changes in the physical characteristics of the sea ice and the overlying snow pack. Results from a k‐means clustering analysis show that variability in the microwave response can be categorized into phenomenological states that were described by Livingstone et al. [IEEE Transactions on Geoscience and Remote Sensing 1987; 25(2): 174–187] as winter, early melt, melt onset and advanced melt. We describe the average thermophysical conditions associated with each one of these ‘ablation states’ and interpret the relative contributions of each to the observed microwave response. Emissivities were calculated and used as part of a descriptive analysis of the seasonal variation of TB. Our results confirm other findings that the strength and pattern of the relationship are frequency dependent and relative to snow and ice dielectric properties. Useful information on the thermodynamic state of the snow–sea‐ice system can be derived from passive microwave data, since the microwave emissions respond to the general seasonal changes associated with the transition from winter to a melt ponded sea ice surface. Copyright © 2001 John Wiley & Sons, Ltd.
Analysis of groundwater exchange for a large plains river in Colorado (USA)
Authors: Sjodin Arne , Lewis William M. , Saunders James F.
Published: August 2002

Complete daily water budget information was assembled for a 105 km segment of the South Platte River in the plains region below Denver, CO, for the period 1983–1993. The data were used in testing the possibility that dependence of alluvial exchange mechanisms on stage height, as shown by models of alluvial exchange, allows alluvial exchange to be predicted continuously over a given reach through use of statistical information on river discharge. The study segment was divided into an upper and a lower reach; daily alluvial exchanges for each reach were estimated by the method of residuals. The two reaches show small (15%) but statistically significant annual differences in rates of exchange. For each reach, there is a seasonal pattern (2·5‐fold oscillation) in alluvial discharge to the channel, reflecting seasonality in recharge of the alluvium by irrigation. At discharges up to 40 m3/s (82nd percentile), alluvial discharge to the channel occurs at a rate independent of river discharge. Above 40 m3/s, net alluvial discharge into the channel is progressively reduced; at 60 m3/s (92nd percentile) there is no net alluvial exchange. At still higher river discharges, water is lost to the alluvium through bank storage at a rate that is linearly related to the logarithm of discharge. Annually, alluvial discharge accounts for 15–18% of water entering the study segment, and alluvial recharge through bank storage accounts for 2–4% of water leaving the segment. Alluvial recharge through bank storage at the highest discharges can, however, exceed low‐flow alluvial discharge rates by five‐fold over short intervals. Even though daily alluvial exchanges vary widely, they can be estimated at r2 values above 80% on the basis of reach, season, and river discharge. Copyright © 2001 John Wiley & Sons, Ltd.
Modelling catchment processes in the Swan–Avon river basin
Authors: Viney Neil R. , Sivapalan Murugesu
Published: August 2002

A conceptual hydrological model, LASCAM, is applied to the Swan–Avon catchment (area 120 000 km2) in Western Australia to predict yields of water, salt, sediment, phosphorus and nitrogen. Each of the nutrients is further discriminated into soluble and particulate components. The model uses a single set of global parameters that are applied to each of the 134 subcatchments. Spatial mapping of the model results shows that yields are closely related to the distribution of rainfall and vegetation cover. Application of the model to various land cover scenarios show that since European settlement in the catchment, there has been a five‐fold increase in streamflow, a 40‐fold increase in sediment yield, and approximately 16‐fold increases in total nutrient yields. Copyright © 2001 John Wiley & Sons, Ltd.
Significance of ice‐induced storage to spring runoff: a case study of the Mackenzie River
Authors: Prowse T. D. , Carter T.
Published: August 2002

For most ice‐covered rivers at northern latitudes, the spring freshet is often the largest hydrologic event of the year. Based on a case study of the Mackenzie River, water released from hydraulic storage due to flow abstraction during the early winter is shown to be a major component of the flow volume that comprises the following spring freshet. The amount of water placed into hydraulic and ice‐growth storage over a 60‐day period was calculated to be equal to 27% of the flow that would normally have occurred during this period if an ice cover had not formed. The amount of water released from this ice‐induced hydraulic storage at the time of break‐up and the concomitant spring snowmelt peak accounted for 15 to 19% of the spring freshet volume, depending on the temporal definition of the ‘release’ period. The ice‐related contribution increases to as much as 25% of freshet volume if the ice growth during the fall depression is also included. Importantly, even this percentage is considered an underestimate since it does not take into account the flow contribution from the melt of the complete winter ice cover. If the ice‐induced storage volume is not accounted for in the spring hydrograph, then the volumes of water from spring snowmelt and/or rainfall would be significantly overestimated. Copyright © 2002 John Wiley & Sons, Ltd.
Identification of known and novel immunogenic T‐cell epitopes from tumor antigens recognized by peripheral blood T cells from patients responding to IL‐2‐based treatment
Authors: Scheibenbogen Carmen , Sun Yuansheng , Keilholz Ulrich , Song Mingxia , Stevanovic Stefan , Asemissen Anne Marie , Nagorsen Dirk , Thiel Eckhard , Rammensee Hans‐Georg , Schadendorf Dirk
Published: August 2002

In previous studies CD8+ T cells specific for melanocyte antigens have been frequently found in melanoma patients responding to interleukin‐2 (IL‐2)‐based therapies. In our study we analyzed the suitability of using circulating T cells from melanoma patients with clinical response after IL‐2‐based therapy to identify novel T‐cell epitopes from defined tumor antigens. Using unstimulated peripheral blood mononuclear cells and the interferon‐γ (IFN‐γ) ELISPOT assay, we studied CD8+ T‐cell responses against 5 peptides from the tumor antigen tyrosinase (Tyr) selected by epitope prediction using an HLA‐A1‐binding computer algorithm. T cells specifically secreting IFN‐γ in response to 3 of these 5 peptides, namely, Tyr (454–463), Tyr (146–156) and Tyr (243‐251), could be detected in 4 of 4 HLA‐A1‐positive patients with clinical response. In contrast, no T‐cell responses against these peptides were seen in 6 HLA‐A1‐positive melanoma patients with progressive disease and in 8 healthy subjects. We could generate specific cytotoxic T lymphocytes (CTL) against Tyr (454–463) using peptide‐pulsed autologous dendritic cells as antigen‐presenting cells. The induced CTLs efficiently killed melanoma cells that express HLA‐A1 and tyrosinase. The peptides Tyr (146–156) and Tyr (243‐251) had recently been identified as CTL epitopes by other groups. Further ex vivo characterization of the T cells reactive against the novel epitope Tyr (454–463) in 1 patient by multicolor flow cytometry showed specific CD3+/CD8+/IFN‐γ+ T cells with frequencies of up to 0.41% of the CD3+/CD8+ T‐cell population. Most of this T‐cell population also expressed granzyme B. Our data confirm that in patients with tumor regressions induced by immunotherapy or chemoimmunotherapy circulating T cells reactive with tyrosinase epitopes can frequently be detected. Peripheral blood T cells from such patients are a valuable source for screening peptides selected by epitope prediction This strategy facilitates the rapid identification of immunogenic T‐cell epitopes that are probable targets of immune‐mediated tumor rejection. © 2002 Wiley‐Liss, Inc.
Independent prognostic significance of HER‐2 oncoprotein expression in pN0 prostate cancer undergoing curative radiotherapy
Authors: Fosså Alexander , Lilleby Wolfgang , Fosså Sophie D. , Gaudernack Gustav , Torlakovic Goran , Berner Aasmund
Published: August 2002

Existing prognostic algorithms for localized prostate cancer (PC) are hampered by poor validation for endpoints other than biochemical relapse such as clinical disease progression or survival. Therefore, the prognostic relevance of Her‐2 (Her‐2/neu, c‐erbB2) protein expression in patients undergoing curative radiotherapy (RT) was compared to widely accepted prognostic factors such as pretreatment prostate‐specific antigen (PSA) levels, biopsy Gleason score and T category of the primary tumor. Biopsies from 112 homogeneously treated patients with T1‐4pN0M0 PC were examined by immunohistochemistry and 37% of cases showed membrane‐bound Her‐2 expression in more than 10% of cancer cells. No definite membrane staining was seen in normal prostate epithelium. With 25 patients dead of PC and a median follow‐up of surviving patients of 71 months (range 48–144), the prognostic relevance of Her‐2 expression was univariately associated with adverse outcome in terms of biochemical or clinical progression‐free survival (B/C‐PFS; p = 0.04), clinical progression‐free survival (C‐PFS; p = 0.02) and disease‐specific survival (DSS; p = 0.02). In multivariate analysis, Her‐2 expression, T category and Gleason score were independently associated with C‐PFS, whereas only Her‐2 expression and Gleason score were associated with DSS. Her‐2 expression and Gleason score together discriminated 2 groups of patients with 5‐year DSS of 95% and 79%, respectively (p < 0.001). Pretreatment PSA levels were associated only with B/C‐PFS but not with C‐PFS or DSS. Together the data show for the first time that expression of Her‐2 is of prognostic relevance in localized PC undergoing RT and suggest that analysis for Her‐2 may improve prognostic algorithms for clinically relevant endpoints other than biochemical relapse. © 2002 Wiley‐Liss, Inc.
Somatic mutations in the BRCA2 gene and high frequency of allelic loss of BRCA2 in sporadic male breast cancer
Authors: Kwiatkowska Eliza , Teresiak Marek , Breborowicz Danuta , Mackiewicz Andrzej
Published: August 2002

Breast cancer occurs rarely in men and risk factors for the disease include germline mutations of the BRCA2 gene. High frequency of allelic loss at the BRCA2 locus has been reported in sporadic breast tumors, but somatic mutations of BRCA2 are very rare. Here we report the first case of somatic BRCA2 mutation in male breast cancer with demonstrated loss of heterozygosity. We analyzed a series of 27 archival samples from male breast cancer patients for BRCA2 mutations and loss of heterozygosity at BRCA2 locus. The mutation analysis of BRCA2 gene was performed using SSCA‐HA and sequencing methods. PCR was used to detect LOH at 3 highly polymorphic microsatellite markers spanning BRCA2 region on 13q by comparing the allelic pattern in matched tumor and blood DNA samples. In this study LOH at the BRCA2 locus was observed in 82.6% of informative cases, confirming previous observations on high frequency of LOH affecting the BRCA2 region in male breast cancer. We identified 5 somatic BRCA2 mutations in a set of 23 sporadic male breast cancers (21%). Two silent and 1 missense alterations were novel BRCA2 variants. Here we also report first somatic frameshift BRCA2 mutation in male breast cancer 8138del5. In 3 tumors with somatic BRCA2 alterations, 1 missense, 1 silent and frameshift LOH at chromosome 13q12‐13 were detected and losses involved a wild–type allele of BRCA2 gene. © 2002 Wiley‐Liss, Inc.
Prospective cohort study of cigarette smoking and colorectal cancer risk in women
Authors: Terry Paul D. , Miller Anthony B. , Rohan Thomas E.
Published: August 2002

Epidemiological studies have consistently found a positive association between cigarette smoking and risk of colorectal adenomas, so the absence of a clear association between smoking and colorectal cancer risk may seem paradoxical. However, if colorectal cancer develops only after an induction period of about 35 years, as has been proposed recently, then studies in which all subjects have fewer than about 35 years between smoking commencement and assessment of outcome would be unlikely to detect this association. Few studies have examined smoking of several decades' duration among women. Therefore, in the cohort study reported here, we used proportional hazards models to estimate hazard ratios relating cigarette smoking to colorectal cancer risk among 89,835 women aged 40–59 years at recruitment into the Canadian National Breast Screening Study, a randomized controlled trial of mammography screening for breast cancer. During an average 10.6 years of follow‐up (936,433 person‐years), a total of 527 women were diagnosed with incident colorectal cancer (363 colon and 164 rectal). We found that smoking was associated with increased risk of rectal cancer 30 years or more after commencement, and especially with smoking of 40 years' duration or longer (hazard ratio=3.14, 95% CI=1.33–7.42). There was little evidence for altered risk of colon cancer. These results, along with those of other recent studies, support the hypothesis that tobacco smoking is an initiator, rather than a promoter, of rectal cancer. However, the results do not support an association with colon cancer risk, even with smoking of very long duration and high intensity. © 2002 Wiley‐Liss, Inc.
Post‐menopausal hormonal therapy and gallbladder cancer risk
Authors: Gallus Silvano , Negri Eva , Chatenoud Liliane , Bosetti Cristina , Franceschi Silvia , La Vecchia Carlo
Published: August 2002

The relation between post‐menopausal hormone replacement therapy (HRT) and gallbladder cancer was analyzed in women above age 45 years, using data of a case‐control study conducted in Italy between 1985 and 1997, on 31 incident, histologically confirmed cases and 3,702 controls in hospital for acute, non‐neoplastic conditions. The multivariate odds ratio (OR) was 3.2 (95% confidence interval: 1.1–9.3) for those who had ever used HRT and the OR tended to rise with longer duration. Although based on small numbers, due to the rarity of the disease, these findings provide the first direct epidemiological evidence of an association between HRT and gallbladder cancer. © 2002 Wiley‐Liss, Inc.
CT7 (MAGE‐C1) antigen expression in normal and neoplastic tissues
Authors: Jungbluth Achim A. , Chen Yao‐Tseng , Busam Klaus J. , Coplan Keren , Kolb Denise , Iversen Kristin , Williamson Barbara , van Landeghem Frank K.H. , Stockert Elisabeth , Old Lloyd J.
Published: August 2002

CT7 (MAGE‐C1) is a member of the cancer testis (CT) antigen family. The present study describes the generation of CT7‐33, a monoclonal antibody (MAb) to CT7, and the preliminary protein expression analysis of CT7 in normal tissues and in a limited number of neoplastic lesions. CT7‐33 was effective in frozen as well as formalin‐fixed, paraffin‐embedded tissues, and immunohistochemistry/reverse transcriptase polymerase chain reaction (RT‐PCR) co‐typing demonstrated antibody specificity. CT7‐33 immunoreactivity in normal adult tissues is restricted to testicular germ cells. In neoplastic lesions, CT7‐33 immunostaining is confined to tumor cells, and the frequency of CT7 protein expression mostly parallels previous mRNA analyses. Whereas colorectal and renal cell carcinomas, as well as sarcomas, exhibit poor or no CT7‐33 staining, carcinomas of the mammary gland and ovary, nonsmall cell lung carcinoma and metastatic melanomas exhibit a high incidence of CT7 protein expression. However, as seen in previous analyses of other CT antigens, the expression pattern is mostly heterogeneous, and tumors with more than 50% of tumor staining are only infrequently encountered. In summary, our study presents a new serologic reagent for the analysis of CT7 on a protein level and confirms what is known with regard to the expression pattern of other CT antigens in tumors: frequent heterogeneity of antigen expression. © 2002 Wiley‐Liss, Inc.
Wnt/β‐catenin signaling suppresses apoptosis in low serum medium and induces morphologic change in rodent fibroblasts
Authors: Ueda Yoshihide , Hijikata Makoto , Takagi Shinji , Takada Ritsuko , Takada Shinji , Chiba Tsutomu , Shimotohno Kunitada
Published: August 2002

Wnt/β‐catenin signaling plays important roles in tumorigenesis in certain tumors as well as during development. However, the mechanism of tumorigenesis mediated by this signaling remains to be elucidated. We investigated the response of rodent fibroblasts to activation of Wnt/β‐catenin signaling by treatment with conditioned medium containing soluble Wnt‐3a protein (W3a‐CM) and by expression of a constitutive active β‐catenin gene harbored by an adenovirus vector. W3a‐CM induced transcriptional activation of a β‐catenin/T‐cell factor (Tcf)‐responsive promoter in rodent fibroblasts such as NIH3T3, Rat‐1, Swiss3T3 and Balb3T3 cells. In these cells, an increase in saturation density and an inhibition of apoptosis and/or promotion of growth in low‐serum medium were induced by treatment with W3a‐CM. In Rat‐1 cells, morphologic changes were also induced. All these alterations were reversible. Moreover, the inhibition of apoptosis of NIH3T3 cells in low‐serum medium and the morphologic changes in Rat‐1 cells, but not the increase in saturation density, were also induced by ectopic expression of a constitutive active β‐catenin gene. These results suggested that activation of Wnt/β‐catenin signaling induces inhibition of apoptosis and morphologic changes in these cells. © 2002 Wiley‐Liss, Inc.
Estimates of the world‐wide prevalence of cancer for 25 sites in the adult population
Authors: Pisani Paola , Bray Freddie , Parkin D. Maxwell
Published: August 2002

In health services planning, in addition to the basic measures of disease occurrence incidence and mortality, other indexes expressing the demand of care are also required to develop strategies for service provision. One of these is prevalence of the disease, which measures the absolute number, and relative proportion in the population, of individuals affected by the disease and that require some form of medical attention. For most cancer sites, cases surviving 5 years from diagnosis experience thereafter the same survival as the general population, so most of the workload is therefore due to medical acts within these first 5 years. This article reports world‐wide estimates of 1‐, 2–3‐ and 4–5‐year point prevalence in 1990 in the population aged 15 years or over, and hence describes the number of cancer cases diagnosed between 1986 and 1990 who were still alive at the end of 1990. These estimates of prevalence at 1, 2–3 and 4–5 years are applicable to the evaluation of initial treatment, clinical follow‐up and point of cure, respectively, for the majority of cancers. We describe the computational procedure and data sources utilised to obtain these figures and compare them with data published by 2 cancer registries. The highest prevalence of cancer is in North America with 1.5% of the population affected and diagnosed in the previous 5 years (about 0.5% of the population in years 4–5 and 2–3 of follow‐up and 0.4% within the first year of diagnosis). This corresponds to over 3.2 million individuals. Western Europe and Australia and New Zealand show very similar percentages with 1.2% and 1.1% of the population affected (about 3.9 and 0.2 million cases respectively). Japan and Eastern Europe form the next batch with 1.0% and 0.7%, followed by Latin America and the Caribbean (overall prevalence of 0.4%), and all remaining regions are around 0.2%. Cancer prevalence in developed countries is very similar in men and women, 1.1% of the sex‐specific population, while in developing countries the prevalence is some 25% greater in women than men, reflecting a preponderance of cancer sites with poor survival such as liver, oesophagus and stomach in males. The magnitude of disease incidence is the primary determinant of crude prevalence of cases diagnosed within 1 year so that differences by region mainly reflect variation in risk. In the long‐term period however different demographic patterns with long‐life expectancy in high‐income countries determine a higher prevalence in these areas even for relatively uncommon cancer sites such as the cervix. © 2002 Wiley‐Liss, Inc.
Hyaluronidase gene profiling and role of HYAL‐1 overexpression in an orthotopic model of prostate cancer
Authors: Patel Sonal , Turner Paul R. , Stubberfield Colin , Barry Eleanor , Rohlff Christian R. , Stamps Alasdair , Tyson Kerry , Terrett Jon , Box Gary , Eccles Suzanne , Page Martin J.
Published: August 2002

The mRNA levels of hyal‐1, hyal‐2, LUCA3 and PH20, the 4 hyaluronidases with demonstrated endoglucosaminidase activity, were extensively profiled in normal and tumor tissues and cell lines, using dot blot analysis and quantitative PCR. In normal tissues, hyal‐1, hyal‐2 and LUCA3 all showed unique patterns of mRNA expression, but were generally of widespread distribution, whereas PH20 mRNA was restricted to testes. In a small set of breast tumor samples, no elevations in hyal‐1, hyal‐2 or LUCA3 mRNA were seen. Hyaluronidase activity measured by a novel assay or zymography was also not elevated in sera from a number of breast cancer patients, compared to sera from normal volunteers. In ex vivo xenograft tumor cell lines, however, hyal‐1 or hyal‐2 mRNA levels were frequently elevated, whereas LUCA3 was only infrequently elevated and PH20 not at all. Two cell lines were engineered to overexpress hyal‐1: a breast cancer line (CAL51) and a prostate cancer line (PC3M). Although the in vitro properties of the hyal‐1 overexpressing cell lines were indistinguishable from the parental cells, the orthotopic growth of hyal‐1 expressing PC3M cells in nu/nu mice resulted in significantly increased numbers of metastases, supportive of a role for hyal‐1 in extravasation and metastatic tumor formation in this model of prostate cancer. © 2001 Wiley‐Liss, Inc.
Settled People Don't Move: On Life Course and (Im‐)Mobility in Sweden
Authors: Fischer Peter A. , Malmberg Gunnar
Published: August 2002

This study analyses the impact on mobility of social ties, life‐course events and local insider advantages. Empirical analyses are based on a comprehensive data‐set covering all movers between the 108 local labour market regions in Sweden in 1994. The empirical investigation is based on individual micro‐data from the TOPSWING database, covering the whole Swedish population. The distribution of major events over the life course in the Swedish population is shown. Furthermore, partial effects of regional economic conditions, individual socio‐economic conditions, family ties, life‐course events, and duration of residence on the probability of staying in a local labour market are estimated using a probit model. The study reveals that age‐specific migration propensities are influenced by a variety of conditions. The analysis lends support for the hypothesis that ties to work and family are major determinants of (im‐)mobility and that the distribution of various life projects influences the age‐specific migration pattern. Furthermore, we see a strong general effect of the previous duration of stay in a place of residence and workplace on the probability of staying, and we regard this as strong empirical evidence of what we call location‐specific insider advantages. People who are, in different ways, deeply settled in a geographical area are very likely to be immobile and to remain residents of that region. Copyright © 2001 John Wiley & Sons, Ltd.
An analytic simplification for the reconstruction problem of electrical impedance tomography
Authors: Belward Catherine , Howes Tony , Forbes Lawrence K.
Published: August 2002

This paper introduces a new reconstruction algorithm for electrical impedance tomography. The algorithm assumes that there are two separate regions of conductivity. These regions are represented as eccentric circles. This new algorithm then solves for the location of the eccentric circles. Due to the simple geometry of the forward problem, an analytic technique using conformal mapping and separation of variables has been employed. © 2002 John Wiley & Sons, Inc. Int J Imaging Syst Technol 12, 9–15, 2002
Development and specification of a service agreement and operational rules for La Khe irrigation system, Ha Dong, Vietnam
Authors: Turral Hugh , Malano Hector , Viet Chien Nguyen
Published: August 2002

The paper describes the process development of a level of service specification for the La Khe irrigation system in Vietnam, with the application of computer simulation, flow monitoring and institutional reform. It shows that technical innovation and institutional development need to go hand in hand, and that effective modernisation of irrigation systems requires a good understanding of existing management and infrastructure constraints. Copyright © 2002 John Wiley & Sons, Ltd.