bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of disperse dye exhaustion, color yield, and colorfastness between polylactide and poly(ethylene terephthalate)
Authors: Yang Yiqi , Huda Shah
Published: October 2003

Ten popular disperse dyes with different energy levels and chemical constitutions were used to compare their exhaustion, color yield, and colorfastness on polylactide (PLA) and poly(ethylene terephthalate) (PET). Only two out of the 10 dyes had exhaustions higher than 80% on PLA at 2% owf. Five out of the 10 dyes had exhaustions less than 50%. All 10 dyes had more than 90% exhaustion on PET, whereas six of them had exhaustions of 98% or higher. There was no obvious pattern as for which energy level or which structure class provided dye exhaustion better than that of others. Although PLA had lower disperse dye exhaustion than that of PET, it had higher color yield. Based on the 10 dyes examined, the color yield of PLA was about 30% higher than that of PET. This means that even with low dye uptake, PLA could have a similar apparent shade depth as that of PET if the same dyeing conditions are applied. Our study supported that the lower reflectance, or reflectivity, of PLA contributes to the higher color yield of PLA than that of PET. A quantitative relation between the shade depth of PLA and PET based on their dye sorption was developed. Disperse dyes examined had lower washing and crocking fastness on PLA than on PET. The differences in class were about 0.5 to 1.0. If the comparison was based on the same dye uptake, the differences might be larger. The differences in light fastness between the two fibers were smaller than that in washing and crocking fastnesses. The light fastness of disperse dyes on PLA is expected to be even better if the comparison is based on the same dye uptake on both fibers. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 90: 3285–3290, 2003
Preparation of thermoplastic elastomers based on silicone rubber and polyethylene by thermomechanical reactive blending: Effects of polyethylene structural parameters
Authors: Jalali‐Arani A. , Katbab A. A. , Nazockdast H.
Published: October 2003

Attempts have been made to prepare thermoplastic elastomers based on polyethylene and silicone rubber by thermomechanical reactive mixing of the two polymers. Occurrence of both grafting and vulcanization of the silicone rubber chains was evidenced by increase in the mixing torque, solvent extraction data, as well as FTIR and DSC analysis. Among different types of polyethylene, linear low‐density polyethylene (LLDPE) showed higher potential to promote reactions between the two phases. The blend based on LLDPE prepared at high temperature and shear rate exhibited distinct rheological behavior with a non‐Newtonian characteristic and higher dynamic viscosity measured by rheomechanical spectroscopy (RMS) than the two individual components at low frequencies. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 90: 3402–3408, 2003
Swelling kinetics of modified poly(vinyl alcohol) hydrogels
Authors: Kim Seon Jeong , Lee Ki Jung , Kim In Young , Lee Young Moo , Kim Sun I.
Published: October 2003

Interpenetrating polymer network (IPN) hydrogels composed of poly(vinyl alcohol) (PVA) and monomer, N‐isopropylacrylamide (NIPAAm), diallyldimethylammonium chloride (DADMAC), or methacrylic acid (MAA) were prepared by using the sequential‐IPN method. The equilibrium swelling ratios of PVA/NIPAAm (VANP), PVA/DADMAC (VADC), and PVA/MAA (VAMA) are 412, 370, and 297 at 25°C, respectively. VANP had the highest swelling ratio in time‐dependent swelling behavior, whereas the swelling ratio of VAMA had the lowest. The n values of VANP, VADC, and VAMA are 0.72, 0.81, and 0.96, respectively. Transport of all IPN hydrogels is anomalous and their transport mechanisms are dominated by a combination of diffusion‐controlled and relaxation‐controlled systems. VAMA has the highest activation energy and VANP has the lowest activation energy. The values of all IPN hydrogels are from 4.66 to 16.49 kJ/mol, which proves that all IPN hydrogels are hydrophilic. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 90: 3310–3313, 2003
Energy‐based predictive criterion for LCP fibrillation in LCP/thermoplastic polymer blends under shear
Authors: Joshi S. C. , Lam Y. C. , Yue C. Y. , Tam K. C. , Li L. , Hu X.
Published: October 2003

This article relates the fibrillation of liquid crystalline polymer (LCP) under shear in its blend with a thermoplastic polymer (TP) to the relative rate of energy utilization in the LCP and TP phases. The development of a criterion based on the energy relationship for predicting LCP fibrillation in the blend is discussed. The formation of LCP fibers in the blends of LCP with polycarbonate (PC), polyethylene naphthalate (PEN), high‐density polyethylene (HDPE), polypropylene (PP), and silica‐filled polypropylene (PP) was studied to validate the criterion and to demonstrate its applicability. For all the blends, viscosity data were obtained by using a capillary rheometer, which was subsequently used to estimate the rate of energy utilization in the LCP and the matrix phases. The predictions based on the proposed criterion were verified through the morphological investigations carried out on the extrudates obtained from the same capillary experiments. The energy‐based criterion was easy to implement, could account for the effect of variable LCP concentration and fillers in the blend, and could provide reliable predictions for a variety of LCP/TP blends. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 90: 3314–3324, 2003
Structure–properties relationship of starch/waterborne polyurethane composites
Authors: Cao Xiaodong , Zhang Lina , Huang Jin , Yang Guang , Wang Yixiang
Published: October 2003

The blend materials from waterborne polyurethane (WPU)/starch (ST) with different contents (10–90 wt %) were satisfactorily prepared by using the solution casting method. Their miscibility, structure, and properties were investigated by wide‐angle X‐ray diffraction (WAXD), scanning electron microscope (SEM), different scanning calorimetry (DSC), dynamic mechanical thermal analysis (DMTA), and the tensile tests, respectively. The results indicated that tensile strength of composite materials not only depended on the starch content, but also related to the microstructure of WPU. The sample WPU2 (1.75 of NCO/OH molar ratio) exhibited hard‐segment order, but WPU1 (1.25 of NCO/OH molar ratio) had no hard‐segment order. The appropriate starch filled into WPU not only decreased the ordered region of soft‐segment matrix, but also hindered the formation of hard‐segment ordered structure. The blend material from 80 wt % WPU1 and 20 wt % starch exhibited better tensile strength (27 MPa), elongation at break (949%), and toughness than others. With an increase of starch content, the WPU matrix with dispersed starch in the blends transited to dual‐phase continuity and then to starch matrix with dispersed WPU. The results suggested that a certain extent of miscibility existed between WPU and starch in the blend materials on the whole composition ratio. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 90: 3325–3332, 2003
Soybean oil based polyisocyanurate cast resins
Authors: Javni Ivan , Zhang Wei , Petrović Zoran S.
Published: October 2003

Two series of polyisocyanurates were prepared from polymeric 4,4′‐diphenylmethane diisocyanate (MDI) and soy‐based or polypropylene oxide polyols by varying isocyanate indexes from 105 to 350. Increasing isocyanate index gave polyisocyanurates with increased thermal stability, flame resistance, tensile strength, modulus, and glass transition. Impact was lower. Soy‐based polyisocyanurates displayed better thermal stability, higher rigidity (modulus), and higher strength than those based on the propylene oxide polyols of the same molecular weight and functionality. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 90: 3333–3337, 2003
Crystallization kinetics of low‐density polyethylene and polypropylene melt‐blended with a low‐Tg tin‐based phosphate glass
Authors: Guschl Peter C. , Otaigbe Joshua U.
Published: October 2003

The nonisothermal and isothermal crystallizations of low‐density polyethylene (LDPE) and polypropylene (PP) in phosphate glass (Pglass)–polymer hybrid blends were studied through differential scanning calorimetry (DSC). As the Pglass volume fraction was increased, the percentage crystallinity decreased. The half‐time for crystallization decreased as the propagation rate constant rose, for both of the polymer matrices, with increasing Pglass concentrations. The Pglass was observed to be a nucleating agent for formation of two‐ or three‐dimensional spherulites in the hybrids. Tensile modulus improved for both of the Pglass–polymer hybrids up to 40% Pglass, but the energy to break decreased. Tensile strength changed slightly with the addition of Pglass to the LDPE matrix, exhibiting a larger value than that of pure LDPE at 30%. The tensile strength decreased as more Pglass was added to the PP matrix. The observed differences between tensile properties of the Pglass–PP and Pglass–LDPE hybrids at identical Pglass volume concentration were found to be consistent with that of the crystallization behavior of the hybrids. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 90: 3445–3456, 2003
Real‐time functional MRI using a PC cluster
Authors: Bagarinao Epifanio , Matsuo Kayako , Nakai Toshiharu
Published: October 2003

A system for the real‐time analysis of functional magnetic resonance imaging (fMRI) time series is evaluated. The system exploits the advantages of parallel computing, coupled with an efficient general linear model (GLM) coefficient estimation algorithm, to overcome several issues constraining the analysis of the whole‐brain fMRI data in real time. The highly parallel, voxel‐wise processing of fMRI data motivated the use of a cluster of personal computers for parallel computation. Aside from gaining a significant increase in computational speed, the PC cluster provides a versatile way to handle the computational requirements of the system. The use of GLM in the supporting software allows substantial parametric analysis to be performed. Results of the real‐time analysis of the whole‐brain fMRI data of a normal subject performing a simple finger‐tapping task demonstrated the capabilities of the system. For a real‐time statistical analysis including real‐time image reconstruction, realignment for motion correction, smoothing, GLM coefficient estimation, statistical analysis, and update of the displayed activation map, the time required to process the data for each image volume is about 1.034 s for a 64 × 64 × 30 image volume and 2.561 s for a 128 × 128 × 20 image volume, less than the TR set to 3 s. © 2003 Wiley Periodicals, Inc. Concepts Magn Reson Part B (Magn Reson Engineering) 19B: 14–25, 2003.
A fast calculation method for magnetic field inhomogeneity due to an arbitrary distribution of bulk susceptibility
Authors: Salomir Rares , de Senneville Baudouin Denis , Moonen Chrit TW
Published: October 2003

A fast calculation method for the magnetic field distribution due to (dynamic) changes in susceptibility may allow real‐time interventional applications. Here it is shown that a direct relationship can be obtained between the magnetic field perturbation and the susceptibility distribution inside the MR magnet using a first order perturbation approach to Maxwell's magneto‐static equations, combined with the Fourier transformation technique to solve partial derivative equations. The mathematical formalism does not involve any limitation with respect to shape or homogeneity of the susceptibility field. A first order approximation is sufficient if the susceptibility range does not exceed 10−4 (or 100 ppm). The formalism allows fast numerical calculations using 3D matrices. A few seconds computation time on a PC is sufficient for a 128 × 128 × 128 matrix size. Predicted phase maps fitted both analytical and experimental data within 1% precision. © 2003 Wiley Periodicals, Inc. Concepts Magn Reson Part B (Magn Reson Engineering) 19B: 26–34, 2003.
Cellular interactions between axon terminals containing endogenous opioid peptides or corticotropin‐releasing factor in the rat locus coeruleus and surrounding dorsal pontine tegmentum
Authors: Tjoumakaris S.I. , Rudoy C. , Peoples J. , Valentino R.J. , Van Bockstaele E.J.
Published: October 2003

Recent evidence suggests that certain stressors release both endogenous opioids and corticotropin‐releasing factor (CRF) to modulate activity of the locus coeruleus (LC)‐norepinephrine (NE) system. In ultrastructural studies, axon terminals containing methionine5‐enkephalin (ENK) or CRF have been shown to target LC dendrites. These findings suggested the hypothesis that both neuropeptides may coexist in common axon terminals that are positioned to have an impact on the LC. This possibility was examined by using immunofluorescence and immunoelectron microscopic analysis of the rat LC and neighboring dorsal pontine tegmentum. Ultrastructural analysis indicated that CRF‐ and ENK‐containing axon terminals were abundant in similar portions of the neuropil and that approximately 16% of the axon terminals containing ENK were also immunoreactive for CRF. Dually labeled terminals were more frequently encountered in the “core” of the LC vs. its extranuclear dendritic zone, which included the medial parabrachial nucleus (mPB). Triple labeling for ENK, CRF, and tyrosine hydroxylase (TH) showed convergence of opioid and CRF axon terminals with noradrenergic dendrites as well as evidence for inputs to TH‐labeled dendrites from dually labeled opioid/CRF axon terminals. One potential source of ENK and CRF in the dorsal pons is the central nucleus of the amygdala (CNA). To determine the relative contribution of ENK and CRF terminals from the CNA, the CNA was electrolytically lesioned. Light‐level densitometry revealed robust decreases in CRF immunoreactivity in the LC and mPB on the side ipsilateral to the lesion but little or no change in ENK immunoreactivity, confirming previous studies of the mPB. Degenerating terminals from the CNA in lesioned rats were found to be in direct contact with TH‐labeled dendrites. Together, these data indicate that ENK and CRF may be colocalized to a subset of individual axon terminals in the LC “core.” The finding that the CNA provides, to dendrites in the area examined, a robust CRF innervation, but little or no opioid innervation, suggests that ENK and CRF axon terminals impacting LC neurons originate from distinct sources and that terminals that colocalize ENK and CRF are not from the CNA. J. Comp. Neurol. 466:445–456, 2003. © 2003 Wiley‐Liss, Inc.
Differential expression of nitric oxide in serotonergic projection neurons: Neurochemical identification of dorsal raphe inputs to rodent trigeminal somatosensory targets
Authors: Simpson Kimberly L. , Waterhouse Barry D. , Lin Rick C.S.
Published: October 2003

The dorsal raphe (DR) is invested with nitric oxide synthase (NOS)‐expressing profiles. To characterize the connections of NO‐containing cells and further assess neurochemical relationships maintained by DR, the transmitter identity of the raphe projection to the trigeminal somatosensory system was examined. Rats were injected with retrograde tracer into vibrissae‐related target areas or with anterograde tracer into DR. NADPH‐diaphorase (NADPHd) histochemistry or NOS‐immunostaining was combined with serotonin (5HT)‐ or serotonin transporter (SERT)‐immunolabeling to examine: 1) the presence of NO in 5HT‐containing axons from DR; 2) the distribution of NO‐containing fibers with respect to other nitrergic profiles in the somatosensory system; and 3) the propensity for individual projection neurons in specific subdivisions of DR to colocalize 5HT and NO. Results confirm that “barrel‐like” patches can be identified in several adult trigeminal relay nuclei by NADPHd histochemistry and demonstrate that fibers from DR contain 5HT and NO. Observations include a high percentage of cortical midline projection neurons which contained NADPHd (70–80%) and coexpressed 5HT. In contrast, ∼40% of retrogradely labeled DR‐thalamus cells in the lateral wing demonstrated NADPHd or 5HT expression, but not both in the same neuron. Colocalization of NADPHd and 5HT within individual DR projection neurons indicates that: i) DR is a source of nitrergic input to trigeminal structures, and ii) NO and 5HT may be simultaneously released to influence information‐processing within somatosensory targets. Disparities in NADPHd expression between retrogradely labeled DR neuronal subpopulations further suggest functional differences in the impact of NO on cortical and subcortical targets. J. Comp. Neurol. 466:495–512, 2003. © 2003 Wiley‐Liss, Inc.
A simple way of quantifying immunostained cell nuclei on the whole histologic section
Authors: Elie Nicolas , Plancoulaine Benoît , Signolle Jehan‐Pierre , Herlin Paulette
Published: October 2003

Background

Quantification of nuclei, immunostained for proliferation or differentiation markers, is widely recommended for prognostication and treatment of numerous solid tumors. However, many problems concerning reproducibility of the results obtained still remain, partially due to the lack of standardization of the method used and to the difficulty of taking into account tumor tissue heterogeneity. Technical solutions exist but they are expensive and time consuming, and their complexity limits their diffusion in routine pathology departments.

Methods

In the present study, we use a simple, fast and inexpensive system of acquisition, a 4,000 dots‐per‐inch slide scanner, to get a single true color numerical image of the whole histologic section. The analysis is done thanks to fully automatic image processing, allowing computation of the stain proportion on the whole histologic section, as well as in “hot spots.”

Results

After having precisely fixed settings of the slide scanner, one can easily detect counterstained and immunostained structures, by image analysis. This simple and stable processing can be done under 6 min.

Conclusions

The association of immunohistochemistry, stable acquisition device and computer‐assisted image analysis provides an objective, reproducible, and easy to standardize quantification of the nuclear markers, in relation to the total tumor tissue architecture. Cytometry Part A 56A:37–45, 2003. © 2003 Wiley‐Liss, Inc.
Flow cytometry and GFP: A novel assay for measuring the import and turnover of nuclear‐encoded mitochondrial proteins in live PC12 cells
Authors: Sirk Daniel P. , Zhu Ziping , Wadia Jehangir S. , Mills Linda R.
Published: October 2003

Background

Mitochondrial protein import is typically measured by adding radiolabeled precursor proteins to isolated mitochondria. We have developed a novel, high‐throughput method for measuring protein import in live differentiated PC12 cells using a tetracycline (Tet) regulated, nuclear encoded, mitochondrially‐targeted GFP fusion protein and flow cytometry.

Methods

We generated a PC12 cell line stably transfected with an inducible GFP fusion protein (GFPmt) targeted to mitochondria. GFPmt PC12 cells were treated with NGF for one week to induce neuronal differentiation in the presence of Tet to silence GFP expression. On day seven GFPmt expression was induced by removal of Tet and these “GFP‐on” cells were exposed to sublethal levels of CCCP (2 μM) for 24 h. At 24 h, the cells were harvested in Ca++‐free PBS and the GFPmt signal in live intact cells was measured using flow cytometry. Since GFPmt is not fluorescent prior to being imported into mitochondria, the GFPmt signal reflected only GFPmt imported to mitochondria. PI was used to gate out contributions from dead cells. Turnover of GFPmt in mitochondria was also assessed; in this case, Tet was added to arrest GFPmt expression in GFP‐on cells, and the subsequent decline of the fluorescent signal, in the absence of any new GFP synthesis, was measured by flow cytometry.

Results

Exposure to 2 μM CCCP for 24 h caused a 61% ± 0.4 decline in GFPmt fluorescence compared to controls. This decline corresponded to a 30% ± 7 decrease in GFPmt protein levels measured by Western blot of mitochondrial fractions, and a 72% ± 5 decline in the import of newly synthesized GFPmt to mitochondria over a 1 h period 24‐h after addition of 2 μM CCCP measured by autoradiography. CCCP partially depolarized mitochondria but was not lethal for up to five days.

Conclusions

This novel GFP‐based flow cytometry assay is a rapid and sensitive technique for quantifying protein import to mitochondria in live neuronal cells. Cytometry Part A 56A:15–22, 2003. © 2003 Wiley‐Liss, Inc.
The place of inpatient care in the treatment of anorexia nervosa: Questions to be answered
Authors: Vandereycken Walter
Published: October 2003

Background

The chance that an anorexia nervosa patient will be hospitalized depends more on circumstantial rather than on scientifically based factors. Although there is a lot of information on the treatment of anorexia nervosa patients in a residential setting, answers to questions relating to the “when,” “where,” and “how” of treatment are subjective. There is no clinical consensus and the paucity of controlled research is hampering the development of an evidence‐based practice.

Results

Increasing economic restraints through managed care policies limit the length of inpatient treatment, which leads to early discharge at a lower body weight, which leads to a higher likelihood of readmissions, which leads to increasing costs.

Discussion

We will highlight important issues in the ongoing debate between economic demands and clinical challenges. Our goal is to stimulate critical reflections and systematic research. © 2003 by Wiley Periodicals, Inc. Int J Eat Disord 34: 409–422, 2003.
Generation mechanism on fiber fuse phenomenon in single‐mode optical fibers
Authors: Shuto Yoshito , Yanagi Shuichi , Asakawa Shuichiro , Nagase Ryo
Published: October 2003

Unsteady‐state thermal conduction process in the single‐mode (SM) optical fiber was theoretically studied with the explicit finite‐difference method. In the numerical calculation it was assumed that the electrical conductivity of the core layer increased rapidly above 1050 °C. The core‐center temperature changed suddenly and reached over ten thousand Kelvin when the optical power of 1 W was input to the core layer heated above 1000 °C. This rapid heating phenomenon also occurred when the optical power was reflected at the edge wall of the thermally produced cavity in the core layer. The occurrence of this phenomenon was restricted by the decrease in either the input optical power or the normalized frequency of the SM optical fiber. © 2003 Wiley Periodicals, Inc. Electron Comm Jpn Pt 2, 86(11): 11–20, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/ecjb.10150
Development of high‐frequency SiC‐MESFETs
Authors: Arai Manabu , Honda Hirotake , Ono Shuichi , Sawazaki Hiroshi , Ogata Makoto
Published: October 2003

With rapid growth of mobile communications represented by portable telephones, further increases in the output of high‐frequency power transistors for the base stations are required. Also, in the fields of satellite communications and radar, realization of high‐power transistors replacing electron tubes such as TWTs and magnetrons is desirable for size reduction, weight reduction, and extension of transmitter life. As a transistor meeting such needs, the metal semiconductor field effect transistor (MESFET) based on silicon carbide (SiC) has been attracting attention. SiC is superior in material characteristics such as the electric breakdown field and thermal conductivity and is expected theoretically to provide high power density as a high‐frequency transistor. To date, higher output power density than MESFETs based on Si and GaAs of the same size has been achieved, including an output power density of 4.2 W/mm at 1 GHz. In this paper, the high‐frequency characteristics of the tested SiC high‐frequency MESFET are presented and trends in research on improvement of the high‐frequency characteristics are described. © 2003 Wiley Periodicals, Inc. Electron Comm Jpn Pt 2, 86(11): 1–10, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/ecjb.10160
Automatic shot size discrimination for a video editing support system
Authors: Kumano Masahito , Ariki Yasuo , Uehara Kuniaki , Shimojo Shinji , Sunto Kenji , Tsukada Kiyoshi
Published: October 2003

Since the advent of the digital era the lack of video coding has been a problem. In order to resolve this problem, the editing work, which takes the most time during the production of video content, must be made more efficient. In general, broadcast video is set up using video grammar, a set of standard principles used for broadcasting any video content. Therefore, in order to make editing work more efficient, a video editing support system which reflects this video grammar must be developed. In order to create this kind of video editing support system, indexing information must be set up beforehand for the raw video shot by the camera operator so as to take advantage of the video grammar. Within the video grammar the particularly important rules have to do with connecting shots. In this paper the authors propose a method to automatically index shot size, along with proposing a video editing support system based on video grammar. © 2003 Wiley Periodicals, Inc. Electron Comm Jpn Pt 2, 86(11): 61–71, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/ecjb.10201
An active noise control system using frequency domain simultaneous perturbation method with a variable perturbation magnitude
Authors: Mori Takashi , Kajikawa Yoshinobu , Nomura Yasuo
Published: October 2003

An active noise control (ANC) system is proposed that uses a new frequency domain simultaneous perturbation (FDSP) method automatically controlling the magnitude of perturbation. The proposed method automatically controls the magnitude of perturbation so that the convergence speed can be improved substantially over the conventional case where the magnitude of perturbation is fixed. Specifically, when the error signal is large, the magnitude of the perturbation is made large, while the latter is reduced when the error signal is small. As a result, the present system resolves the problem of instability caused by the block process and also the step size can be set to a larger value. The present control is effective when the magnitude of perturbation needs to be set small. In particular, if the magnitude of perturbation is 0.08, the convergence speed is improved by more than 50 times. Also, the present control is effective for suppression of the noise generated due to addition of perturbation. © 2003 Wiley Periodicals, Inc. Electron Comm Jpn Pt 3, 87(2): 43–53, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/ecjc.10112
Improvement of accuracy and stability in numerically solving hyperbolic equations by IDO (interpolated differential operator) scheme with Runge‐Kutta time integration
Authors: Yoshida Hiroshi , Aoki Takayuki , Utsumi Takayuki
Published: October 2003

In order to solve hyperbolic partial differential equations by means of the Interpolated Differential Operator (IDO) scheme, time integration of the dependent variable has been carried out by Taylor expansion, and time differentiation has been performed by replacing it with a spatial differentiation. However, in such a method, the time accuracy is limited by the order of the interpolation function and in addition the spatial accuracy is not sufficient in multidimensional problems due to the complexity of the calculations. In terms of numerical stability, the stable region indicated by the CFL (Courant‐Friedrich‐Levy) number is narrow. Hence, in order to improve the space‐time accuracy and to secure numerical stability, time integration by the Runge‐Kutta method is applied. Further, a method for increasing the order of the Runge‐Kutta method without increasing the computational cost is proposed, taking advantage of the characteristics of the IDO scheme with the physical quantity and its spatial derivative as the dependent variables. The two‐dimensional advection equation and the one‐dimensional wave equation are solved and the results are quantitatively compared with those obtained by the conventional Taylor expansion. Also, in order to demonstrate the adaptability of this approach to practical problems, we consider Williamson's test case 5 for the shallow‐water equation in spherical geometry. It is found that the Runge‐Kutta method for multiple dimensions yields accuracy and stability higher than those of the Taylor expansion, demonstrating the effectiveness of the approach. © 2003 Wiley Periodicals, Inc. Electron Comm Jpn Pt 3, 87(2): 33–42, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/ecjc.10127
Hereditary renal carcinogenesis fitting Knudson's two‐hit model: Genotype, environment, and phenotype
Authors: Hino Okio
Published: October 2003

Cancer is a heritable disorder of somatic cells. Environment and heredity both operate in the origin of human cancer. The Eker (Tsc2 gene mutant) rat model of hereditary renal carcinoma (RC) is an example of Mendelian dominantly inherited predisposition to a specific cancer in an experimental animal. To the best of our knowledge, this was the first isolation of a Mendelian dominantly predisposing cancer gene in a naturally occurring animal model. Recently, we discovered a new hereditary renal carcinoma in the rat in Japan, and the rat was named the “Nihon” rat, and its predisposing (Nihon) gene could be a novel renal tumor suppressor gene. We present these unique models, comparing these two predisposing genes (both are located on rat chromosome 10), for the study of problems in carcinogenesis, for instance, species‐specific difference in tumorigenesis, cell stage and tissue/cell‐type specific tumorigenesis, multistep carcinogenesis, modifier gene(s) in renal carcinogenesis, cancer prevention, and the development of the therapeutic treatments that can be translated to human patients, as well as how environmental factors interact with cancer susceptibility gene(s). © 2003 Wiley‐Liss, Inc.
NF2: The wizardry of merlin
Authors: Xiao Guang‐Hui , Chernoff Jonathan , Testa Joseph R.
Published: October 2003

Neurofibromatosis type II (NF2) is an autosomal dominant cancer syndrome characterized by the formation of tumors of the nervous system, particularly schwannomas and meningiomas. TheNF2gene is also implicated in the development of sporadic schwannomas and meningiomas, as well as tumor types seemingly unrelated to the NF2 disorder, such as malignant mesotheliomas. Inactivation ofNF2occurs by a “two‐hit” mechanism, as proposed by Al Knudson, and theNF2gene behaves as a classical tumor suppressor gene. TheNF2gene product, merlin, exhibits homology with the ezrin–radixin–moesin family of membrane–cytoskeleton‐linking proteins. During the past several years, there has been intensive investigation aimed at elucidating the mechanisms underlying merlin's functions. In this review, we summarize the involvement ofNF2inactivation in tumorigenesis. We also discuss observations implicating merlin in cell motility and cell proliferation, with a focus on recent findings linking merlin to Rac signaling. © 2003 Wiley‐Liss, Inc.
Genetic hits and mutation rate in colorectal tumorigenesis: Versatility of Knudson's theory and implications for cancer prevention
Authors: Bellacosa Alfonso
Published: October 2003

The multistep model of carcinogenesis is now widely accepted for colorectal cancer and other common epithelial tumors of the adult. The challenges ahead are to define the number of genetic hits necessary for conversion of a normal cell into a cancer cell and to determine whether the observed increase in the mutation rate (mutator phenotype) is required. The beauty of Knudson's two‐hit theory is its ability to explain diverse experimental situations and guide specific predictions, including some directly relevant to cancer prevention. © 2003 Wiley‐Liss, Inc.
Targeting tumor cells by enhancing radiation sensitivity
Authors: McKenna W. Gillies , Muschel Ruth J.
Published: October 2003

The work of Al Knudson created the paradigm in which we see cancer as a result of the accumulation of multiple mutations. Our goal has been to exploit these mutations to develop strategies to enhance therapy for cancer by targeting the malignant cell while sparing the normal tissue. In studying the RAS oncogene, we observed that its expression when activated resulted in enhanced radioresistance. Conversely, inhibition of RAS made cells with activated RAS more radiosensitive. Hence, we postulated that it would be possible to sensitize tumors with RAS mutations to radiation without affecting the sensitivity of the normal tissue in patients with such tumors. This proved to be the case in animal models and has led to current clinical trials. These studies raised the question of identifying the downstream effectors of RAS that are responsible for altering the radiosensitivity of cells. We have found that phosphoinositide‐3‐kinase (PI3 kinase) is a critical component of this pathway. Blocking PI3 kinase enhanced the radiation response in vitro or in vivo of cells actively signaling through that pathway, but did not affect cells not actively signaling through PI3 kinase at the time of irradiation. Identification of tumors with active signaling in this pathway by immunohistochemical staining for phosphorylated AKT, the downstream target of PI3 kinase correlated with those patients for which radiation failed to achieve local control. Thus, characterization of the active signaling pathways in a given tumor might enable the selection of patients likely to respond to radiation. Pathways upstream from RAS may also be useful targets to consider for enhancing radiation therapy. Epidermal growth factor receptor (EGFR), which is upstream of PI3 kinase, may also mediate resistance through a common pathway. In addition to EGFR and RAS, PTEN can also regulate the PI3 kinase pathway. Identifying a common signal for EGFR, RAS, and PTEN that results in radiation resistance may uncover targets for developing molecular‐based radiosensitization protocols for tumors resistant to radiation and thus lead to improvement of local control. © 2003 Wiley‐Liss, Inc.
Detection of point mutations of the Axin1 gene in colorectal cancers
Authors: Jin Li‐Hua , Shao Qiu‐Jie , Luo Wen , Ye Zhi‐Yun , Li Qing , Lin Sheng‐Cai
Published: October 2003

Axin is a recently identified tumor suppressor that plays an important role in liver and colon cancers. To gain further insights into the structure and function of Axin in controlling cell growth, we analyzed 54 colorectal cancer tissues for mutations in AXIN1 gene. We employed PCR amplification with 23 sets of primers against introns that encompassed the whole coding region of AXIN1 followed by single‐strand conformation polymorphism (SSCP) analysis. After subcloning and sequencing analysis of the reamplified DNA from the aberrant bands, we found, in addition to 3 silent mutations, 6 misssense point mutations in different functionally important regions. The missense mutation rate is hence 11%, suggesting that Axin deficiency may contribute to the onset of colorectal tumorigenesis. © 2003 Wiley‐Liss, Inc.
Nonsteroidal anti‐inflammatory drugs inhibit growth of human neuroendocrine tumor cells via G1 cell‐cycle arrest
Authors: Detjen Katharina M. , Welzel Martina , Wiedenmann Bertram , Rosewicz Stefan
Published: October 2003

Therapeutic options to inhibit growth of human NETs of the GEP system are limited. Since NSAIDs might provide an antiproliferative treatment alternative with acceptable toxicity, we examined the effects of different NSAIDs on growth and survival in a representative set of human GEP NET cell lines. Growth and apoptosis were determined based on cell numbers, cell‐cycle analyses, kinase assays, DNA fragmentation and PARP cleavage. Expression of COX and cell cycle–regulatory molecules was examined by immunoblotting and reporter gene assays. Depending on the drug and cell line investigated, NSAID treatment resulted in profound growth inhibition of GEP NET cells. Growth‐inhibitory effects were achieved with either COX‐2 selective (NS398) or unselective (indomethacin, sulindac) compounds. Cell‐cycle analyses documented a G1 arrest in NSAID‐treated GEP NET populations. In addition, 100 μM sulindac or indomethacin induced apoptosis. All 3 COX inhibitors prevented CDK‐2 activation. In parallel to the NSAID‐mediated reduction of CDK‐2 activity, p21cip‐1 promoter activity and cellular p21cip‐1 levels increased and p21cip‐1 was sequestered into CDK‐2 complexes. Thus, the G1 arrest likely resulted from p21cip‐1‐dependent inhibition of CDK‐2 activity. At therapeutically relevant concentrations, sulindac significantly reduced GEP NET cell numbers, whereas IFN‐α and octreotide remained ineffective. The extent of growth inhibition in GEP NETs was comparable to the antiproliferative effects of sulindac in established NSAID‐sensitive cell models. NSAIDs acted as potent antiproliferative agents in GEP NET cells via G1 cell‐cycle arrest and might therefore offer a therapeutic alternative to current treatment modalities. © 2003 Wiley‐Liss, Inc.
Generation of a highly stable, internalizing anti‐CD22 single‐chain Fv fragment for targeting non‐Hodgkin's lymphoma
Authors: Arndt Michaela A.E. , Krauss Jürgen , Schwarzenbacher Robert , Vu Bang K. , Greene Shailen , Rybak Susanna M.
Published: October 2003

The generation of a single chain Fv (scFv) fragment derived from the anti‐CD22 monoclonal antibody LL2 resulted in a molecule with good antigen binding but very poor stability properties, thus hampering its clinical applicability. Here we report on the construction of an engineered LL2 scFv fragment by rational mutagenesis. The contribution of uncommon wild‐type sequence residues for providing stability to the conserved common core structure of immunoglobulins was examined. Aided by computer homology modeling, 3 destabilizing residues within the core of the wild‐type VH domain were identified. Owing to the conserved nature of the buried core structure, mutagenesis of these sites to respective consensus residues markedly stabilized the molecule but did not influence its antigen binding properties: the engineered scFv MJ‐7 exhibited exceptional biophysical stability with a half‐life not reached after 6 days of incubation in human serum at 37°C, while fully retaining the epitope specificity of the monoclonal antibody, and antigen binding affinity of the wild‐type scFv. Furthermore, both the monoclonal antibody LL2 and the engineered scFv fragment became fully internalized after only 30 min of incubation at 37°C with CD22+ tumor cells. These properties predict scFv MJ‐7 could become a novel powerful tool to selectively deliver cytotoxic agents to malignant CD22+ cells. © 2003 Wiley‐Liss, Inc.
Long‐term risk of second malignant neoplasms after neuroblastoma in childhood: Role of treatment
Authors: Rubino Carole , Adjadj Elisabeth , Guérin Sylvie , Guibout Catherine , Shamsaldin Akhtar , Dondon Marie‐Gabrielle , Valteau‐Couanet Dominique , Hartmann Olivier , Hawkins Mike , de Vathaire Florent
Published: October 2003

The aim of our study was to quantify the risk of second malignant neoplasms (SMNs) among long‐term survivors of neuroblastoma and to study the influence of treatment on this risk. We studied data from 544 5‐year survival patients diagnosed with neuroblastoma before age 16 years at 8 French and British treatment centres from 1948 to 1986. After an average follow‐up of 15 years (range, 5–38 years), 12 children developed a total of 13 SMNs, whereas 1.19 were expected from general population rates. Among these SMNs, there were 5 thyroid and 3 breast cancers. Increases of the risks of SMN were observed with time since neuroblastoma diagnosis and attained age. In a multivariate analysis, the relative risk of SMN associated with radiotherapy was 4.3 (95% CI 0.8–78), whereas no increased risk of SMN was associated with the administration of chemotherapy as a whole (RR = 0.4, 95% CI 0.1–1.9). Young children treated for a neuroblastoma have significantly increased risks of SMN over 3 decades of follow‐up. Radiotherapy treatment was found to be an important risk factor for developing SMNs, whereas no effect of chemotherapy was evidenced. Although our findings reflect the late effects of past therapeutic modalities, they underscore the importance of long‐term surveillance of young children treated for a neuroblastoma. For these patients, many more years of follow‐up are required to appreciate their overall risks of treatment‐related SMNs. © 2003 Wiley‐Liss, Inc.
Relative risk of prostate cancer for men with affected relatives: Systematic review and meta‐analysis
Authors: Watkins Bruner Deborah , Moore Dirk , Parlanti Alicia , Dorgan Joanne , Engstrom Paul
Published: October 2003

An increased risk of prostate cancer associated with a family history of prostate cancer has been documented in multiple published reports. Risk has been shown to vary by degree of relationship and age of onset of disease in the affected relative. Several studies, using various designs, have estimated the relative risk (RR) for these associations. The purpose of our study was to identify and summarize published reports on the relationship between risk of prostate cancer and family history, which is defined as having a father, brother, any first‐ or second‐degree relative or other relative affected with prostate cancer. A Medline and manual search from 1982 to 2000 identified 24 studies that reported RR and confidence intervals (CI) and satisfied inclusion criteria. Pooled RR estimates based upon a weighted average model were as follows: any affected family member RR = 1.93, CI 1.65–2.26; affected first‐degree relative RR = 2.22, CI 2.06–2.40; affected second‐degree relative RR = 1.88, CI 1.54–2.30; father with prostate cancer RR = 2.12, CI 1.82–2.51; and brother with prostate cancer RR = 2.87, CI 2.21–3.73). Statistical comparison of pooled data demonstrated that the RR is significantly higher for affected brother than for affected father (p < 0.03). A sensitivity analysis demonstrated that these results are robust with respect to population bias. This meta‐analysis confirms that risk of prostate cancer is associated with family history of disease and improves the quantification of this risk. © 2003 Wiley‐Liss, Inc.
Condom use promotes regression of cervical intraepithelial neoplasia and clearance of human papillomavirus: A randomized clinical trial
Authors: Hogewoning Cornelis J.A. , Bleeker Maaike C.G. , van den Brule Adriaan J.C. , Voorhorst Feja J. , Snijders Peter J.F. , Berkhof Johannes , Westenend Pieter J. , Meijer Chris J.L.M.
Published: October 2003

Women with persistent HPV infections have increased risk of progressive CIN lesions. Transmission of HPV between sexual partners might maintain viral infection and, consequently, may influence the clinical course of CIN. We investigated the effect of condom use on regression of CIN lesions and on clearance of HPV. Women with CIN and their male sexual partners were randomized for condom use (condom group n = 72 and noncondom group n = 76). They were conservatively managed and followed every 3–6 months by colposcopy, cytology and HPV testing by GP5+/6+ PCR. Baseline cervical biopsy specimens were taken. Median follow‐up time for women was 15.2 months (range 3.0–85.4). Outcomes of interest were clinical regression of CIN at colposcopy and clearance of HPV. Outcomes were assessed in 64 women of the condom group and 61 women of the noncondom group. Women in the condom group showed a 2‐year cumulative regression rate of 53% vs. 35% in the noncondom group (p = 0.03). The 2‐year cumulative rates of HPV clearance were 23% vs. 4%, respectively (p = 0.02). Although lower regression rates were found if women were HPV‐positive and had ≥CIN2 lesions at baseline, effects of condom use were found both in women with CIN1 and in women with ≥CIN2 lesions. Condom use promotes regression of CIN lesions and clearance of HPV. © 2003 Wiley‐Liss, Inc.
HER‐2 and TOP2A coamplification in urinary bladder cancer
Authors: Simon Ronald , Atefy Ramin , Wagner Urs , Forster Thomas , Fijan André , Bruderer James , Wilber Kim , Mihatsch Michael J. , Gasser Thomas , Sauter Guido
Published: October 2003

HER‐2/NEU is one of the most frequently amplified oncogenes and a potential therapeutic target in bladder cancer. In breast cancer, the adjacent TOP2A gene, the molecular target for several anticancer drugs, is frequently coamplified together with HER‐2. To study the amplification and expression of TOP2A and HER‐2 and associations with tumor phenotype and clinical outcome in bladder cancer, a tissue microarray containing 2,317 bladder tumor samples was analyzed by FISH and immunohistochemistry. Overall amplification frequencies were 6.3% for HER‐2 and 1.5% for TOP2A. Amplifications were most frequently seen in advanced‐stage (pT2–4) tumors (HER‐2 13.8%, TOP2A 3.4%). Of HER‐2‐amplified tumors, 56% also had alterations of TOP2A, including 14.7% coamplifications, 33.3% gains and 8% deletions. Only 17.6% of TOP2A amplifications occurred independently of HER‐2 alterations. Both HER‐2 and TOP2A amplifications were significantly associated with advanced tumor stage (HER‐2
p < 0.0001, TOP2A
p = 0.0218), high grade (p < 0.0001 for both) and protein overexpression (p < 0.0001 for both). TOP2A amplification and overexpression were linked to shortened survival in muscle‐invasive tumors (p = 0.0042 and 0.0077, respectively). In summary, our data suggest that HER‐2 amplifications are frequently linked to alterations of the TOP2A gene in bladder cancer. The anatomy of the 17q12‐q21 amplicon may be important for response to therapies targeting HER‐2 or TOP2A. © 2003 Wiley‐Liss, Inc.
Identification of a sperm protein 17 CTL epitope restricted by HLA‐A1
Authors: Chiriva‐Internati Maurizio , Wang Zhiqing , Pochopien Stephanie , Salati Emanuela , Lim Seah H.
Published: October 2003

Sperm protein 17 (Sp17) is a novel cancer‐testis antigen. We previously reported the successful generation of Sp17‐specific HLA‐A1‐restricted cytotoxic T‐lymphocytes (CTLs) from the peripheral blood of a healthy donor using a recombinant Sp17 protein. These CTLs were able to kill not only target cells pulsed with the recombinant protein but also fresh Sp17+ tumor cells. In the present study, we have identified a nonapeptide sequence within the Sp17 protein that is predicted to have a high binding affinity for the HLA‐A1 molecules. We generated the synthetic nonapeptide and successfully propagated a peptide‐specific CTL line. We confirmed that peptide Sp17103–111 (ILDSSEEDK) contains an Sp17 CTL epitope restricted by HLA‐A1 and identified amino acid residues 104, 107, 109 and 110 as crucial for the CTL lysis. Our findings therefore provide the tool for the characterization of CD8 T‐cell function in vivo and generation of epitope‐specific treatment strategies. © 2003 Wiley‐Liss, Inc.