bluuebunny/crossref_metadata_2025 huggingface dataset:
Serum human glandular kallikrein (hK2) and insulin‐like growth factor 1 (IGF‐1) improve the discrimination between prostate cancer and benign prostatic hyperplasia in combination with total and %free PSA
Authors: Scorilas Andreas , Plebani Mario , Mazza Saverio , Basso Daniela , Soosaipillai Antoninus R. , Katsaros Nikos , Pagano Francesco , Diamandis Eleftherios P.
Published: January 2003

BACKGROUND

There is growing evidence describing an association of hK2 and IGFs with cancer. The aim of this study is to investigate the differences in serum levels of hK2 and IGFs in a large group of patients with benign prostatic hyperplasia (BPH) or prostatic carcinoma (CaP) and to examine the value of these variables, as well as their various combinations with PSA, for discriminating between these two clinical entities.

METHODS

Human glandular kallikrein 2 (hK2), insulin‐like growth factor‐1 (IGF‐1), free and total PSA concentrations were measured with non‐competitive immunological procedures. Receiver operating characteristic (ROC) analysis as well as univariate and multivariate logistic regression analysis were performed to investigate the potential utility of the various markers and their combinations for discriminating between BPH and CaP.

RESULTS

hK2 and IGF‐1 concentrations were increased in CaP patients, in comparison to BPH patients. hK2/free PSA and free/total PSA ratios (area under the curve, AUC = 0.70) were stronger predictors of prostate cancer than the IGF‐1/total PSA ratio (AUC = 0.56) in the group of patients with total PSA <4 μg/L. The hK2/free PSA ratio (AUC = 0.74) was found to have significant discriminatory value in patients with total PSA within the “gray zone” (4–10 μg/L). Multivariate logistic regression models confirmed the observed relationships and identified IGF‐1/free PSA and hK2/free PSA as independent predictors of CaP.

CONCLUSIONS

hK2/free PSA and IGF‐1/free PSA ratios may be useful adjuncts in improving patient selection for prostate biopsy. Prostate 54: 220–229, 2003. © 2002 Wiley‐Liss, Inc.
Experimental therapy of human prostate cancer by inhibiting MDM2 expression with novel mixed‐backbone antisense oligonucleotides: In vitro and in vivo activities and mechanisms
Authors: Wang Hui , Yu Dong , Agrawal Sudhir , Zhang Ruiwen
Published: January 2003

BACKGROUND

MDM2 oncogene is overexpressed in many human cancers including prostate cancer and MDM2 levels are associated with poor prognosis. This study was undertaken to investigate the functions of MDM2 oncogene in prostate cancer growth and the value of MDM2 as a drug target for prostate cancer therapy by inhibiting MDM2 expression.

METHODS

Antisense anti‐human‐MDM2 mixed‐backbone oligonucleotide and its mismatch control were tested in in vitro and in vivo human prostate cancer models (LNCaP, DU 145, and PC‐3) for anti‐tumor activity. Targeted gene products and related proteins were analyzed and the anti‐tumor activity was determined when the oligonucleotides were used alone or in combination with cancer therapeutics.

RESULTS

The antisense oligonucleotide specifically inhibited MDM2 expression in a dose‐ and time‐dependent manner, resulting in significant anti‐tumor activity in vitro and in vivo. In LNCaP cells, p53 and p21 levels were elevated. The antisense oligonucleotide also potentiated the effects of p53 activation and p21 induction by chemotherapeutic agents 10‐hydroxycamptothecin, adriamycin, 5‐fluorouracil, and paclitaxel. In DU145 cells, following inhibition of MDM2 expression, p21 levels were elevated although p53 levels remained unchanged. In both cell lines, the antisense oligonucleotide inhibited tumor cell growth and induced apoptosis in vitro. In a dose‐dependent manner, the antisense oligonucleotide showed anti‐tumor activity in nude mice bearing DU145 or PC‐3 xenografts. It significantly increased therapeutic effectiveness of the chemotherapeutic agent irinotecan and slightly improved the effects of paclitaxel and Rituxan.

CONCLUSIONS

These results indicate that MDM2 has a role in prostate tumor growth through both p53‐dependent and p53‐independent mechanisms, indicating that MDM2 inhibitors have a broad spectrum of anti‐tumor activities in human prostate cancers regardless of p53 status. Prostate 54: 194–205, 2003. © 2002 Wiley‐Liss, Inc.
Bioequivalence and the pharmaceutical industry
Authors: Patterson Scott D. , Jones Byron
Published: January 2003

Since the early 1990s, average bioequivalence (ABE) studies have served as the international regulatory standard for demonstrating that two formulations of drug product will provide the same therapeutic benefit and safety profile when used in the marketplace. Population (PBE) and individual (IBE) bioequivalence have been the subject of intense international debate since methods for their assessment were proposed in the late 1980s and since their use was proposed in United States Food and Drug Administration guidance in 1997.

Guidance has since been proposed and finalized by the Food and Drug Administration for the implementation of such techniques in the pioneer and generic pharmaceutical industries. The current guidance calls for the use of replicate design and of cross‐over studies (cross‐overs with sequences TRTR, RTRT, where T is the test and R is the reference formulation) for selected drug products, and proposes restricted maximum likelihood and method‐of‐moments techniques for parameter estimation. In general, marketplace access will be granted if the products demonstrate ABE based on a restricted maximum likelihood model. Study sponsors have the option of using PBE or IBE if the use of these criteria can be justified to the regulatory authority. Novel and previously proposed SAS®‐based approaches to the modelling of pharmacokinetic data from replicate design studies will be summarized.

Restricted maximum likelihood and method‐of‐moments modelling results are compared and contrasted based on the analysis of data available from previously performed replicate design studies, and practical issues involved in the application of replicate designs to demonstrate ABE are characterized.

It is concluded that replicate designs may be used effectively to demonstrate ABE for highly variable drug products. Statisticians should exercise caution in the choice of modelling procedure. Copyright © 2002 John Wiley & Sons, Ltd.
Dealing with selective dropout in clinical trials
Authors: Möcks Joachim , Köhler Walter , Scott Martin , Maurer Joerg , Budde Michael , Givens Sam
Published: January 2003

Clinical trials in severely diseased populations often suffer from a high dropout rate that is related to the investigated target morbidity. These dropouts can bias estimates and treatment comparisons, particularly in the event of an imbalance. Methods to describe such selective dropout are presented that use the time in study distribution to generate so‐called population evolution charts. These charts show the development of a distribution of a covariate or the target morbidity measure as it changes as a result of the dropout process during the follow‐up time. The selectiveness of the dropout process with respect to a variable can be inferred from the change in its distribution. Different types of selective dropout are described with real data from several studies in metastatic bone disease, where marked effects can be seen. A general strategy to cope with selective dropout seems to be the inclusion of dropout events into the endpoint. Within a time‐to‐event analysis framework this simple approach can lead to valid conclusions and still retains conservative elements. Morbidity measures that are based on (recurrent) event counts react differently in the presence of selective dropout. They differ mainly in the way dropout is included. One simple measure achieves good performance under selective dropout by introducing a non‐specific penalty for premature study termination. The use of a prespecified scoring system to assign a weight for each works well. This simple and transparent approach performs well even in the presence of unbalanced selective dropout. Copyright © 2002 John Wiley & Sons, Ltd.
Changing times in pharmaceutical statistics: 2000‐2020
Authors: Day Simon
Published: January 2003

In a previous paper we considered how pharmaceutical statistics had changed between 1980 and 2000. In this paper we go on to consider some of the likely influences and changes in the world of pharmaceutical statistics over the next twenty years. Statistical research by pharmaceutical companies is supported, although its direct value in boosting company profits is challenged. The duality between fraud and conflict of interest is explored, particularly with regard to data and safety monitoring boards. Political correctness within clinical trials and (allegedly) better patient‐oriented outcomes is questioned and the whole notion of intention‐to‐treat and per‐protocol analyses is rejected in favour of pragmatic trials and explanatory trials. The dominance of SAS software within the industry is explored and the possibility for change considered. Finally, whilst the future of pharmaceutical companies is not addressed, the impact of future mergers, collaborations and take‐overs between clinical research organizations is considered. Copyright © 2002 John Wiley & Sons, Ltd.
Low‐energy electron diffraction study of atomic structure of Sc–O/W(100) surface acting as Schottky emitter at high temperatures
Authors: Iida S. , Tsujita T. , Nagatomi T. , Takai Y.
Published: January 2003

Low‐energy electron diffraction (LEED) was used to investigate the atomic structure of an Sc–O/W(100) surface acting as a Schottky emitter in order to elucidate a marked reduction in the work function of the Sc–O/W(100) Schottky emitter surface. The results of our LEED observation of the Sc–O/W(100) surface at room temperature revealed that a p(2 × 1) and p(1 × 2) double‐domain structure is formed on the surface. This reconstructed structure exhibited no changes when heated to 1400 K, and continued to remain stable even when held at 1400 K. These results strongly suggest that the p(2 × 1) and p(1 × 2) double‐domain structure is formed by scandium–oxygen electric dipoles on the W(100) surface, leading to a marked reduction in the work function of the Sc–O/W(100) surface at the operating temperature of the Sc–O/W(100) Schottky emitter. Copyright © 2003 John Wiley & Sons, Ltd.
Electron emission characteristics of ZrO/W electron sources with a wide range of tip radii
Authors: Sakawa Seiichi , Tsunoda Katsuyoshi , Terui Yoshinori
Published: January 2003

Emitters of ZrO/W with a wide range of tip radii (0.43–4.2 µm) were prepared and evaluated. A unique tip‐forming method using local Joule heating was developed to make the tip radii >2 µm. The tip radius dependency of the energy spread agrees qualitatively with the energy spread calculated by Knauer's formula when evaluating the Boersch effect. Emitters with tip radii >2 µm show their energy spread to be close to the theoretically predicted energy spread without the Boersch effect. Even at 400 µA sr−1 operation, the emitter with a 4.2 µm tip radius shows a 0.47 eV full width at half‐maximum (FWHM) energy spread and the emitter with a 0.43 µm tip radius shows a 0.98 eV FWHM energy spread. Emitters with tip radii >2 µm, fabricated by local Joule heating, are expected to suppress chromatic aberration in low beam voltage application and thus would be helpful for industrial uses such as critical dimension and defect review SEM. Copyright © 2003 John Wiley & Sons, Ltd.
Structural characterization of randomly and vertically oriented carbon nanotube films grown by chemical vapour deposition
Authors: Ikuno Takashi , Furuta Hiroshi , Yamamoto Tetsuro , Takahashi Syunji , Kamizono Motoki , Honda Shin‐ichi , Katayama Mitsuhiro , Hirao Takashi , Oura Kenjiro
Published: January 2003

We have investigated the structures of randomly and vertically oriented carbon nanotubes grown by thermal chemical vapour deposition and dual‐r.f.‐plasma‐enhanced chemical vapour deposition, respectively. The randomly oriented carbon nanotubes have a bamboo‐like structure, whereas the vertically oriented carbon nanotubes have a multi‐shell shape. Both types of nanotubes have a metal nanoparticle at the tip. The field emission property of the randomly oriented nanotube films was better than that of the vertically oriented nanotube films. This result indicates that more emission sites exist at the body than at the tip of the nanotubes. Copyright © 2003 John Wiley & Sons, Ltd.
High‐resolution AES study of Ar+‐irradiated graphite
Authors: Hashimoto Hiroyuki , Watanabe Masatoshi , Nishiuma Satoru , Nakamura Kumi , Yoshida Shigeki
Published: January 2003

High‐resolution AES (HR‐AES) has been used to study the electronic state of Ar+‐irradiated graphite in which the increase in the partial charge density caused by the lattice damage has been indicated. At doses of <5 × 1011 Ar+ cm−2, which was reported as a maximum value to avoid the overlapping cascades, neither plasmon energies nor the work function in highly oriented pyrolytic graphite (HOPG) was changed. Increase in the work function was observed in Ar+‐irradiated graphite with doses in the range of ∼1 × 1013 to 1 × 1015 ions cm−2, and Ar+ at a dosage of 3 × 1014 ions cm2 increased the work function of HOPG by ∼0.2 eV. This implies an increase in the average electron density at the surface or an increase in the local electron density at a torn graphite edge. The π plasmon energy was decreased by an irradiation of >1 × 1014 Ar+ cm−2 and the π + σ plasmon energy was decreased slightly at >1 × 1015 Ar+ cm−2. The difference in the two energy variations in the range of 1 × 1014 to 1 × 1015 Ar+ cm−2 shows that the possibility of changes in the resonance energy and/or the lattice parameters is present if the π/σ electron ratio does not change. Copyright © 2003 John Wiley & Sons, Ltd.
Copper nanostructure formation and structure analysis on hydrogen‐terminated Si(111) surface
Authors: Kuroiwa N. , Fukushima Y. , Rajasekar P. , Neddermeyer H. , Jalochowski M. , Bauer E. , Yasue T. , Koshikawa T.
Published: January 2003

The growth of Cu nanostructures on the hydrogen‐terminated Si(111) surface was studied by scanning tunnelling microscopy (STM). On the hydrogen‐terminated Si(111) surface, small Cu nanostructures scatter mainly on the terraces and a few structures along the steps and domain boundaries at a deposition temperature of ∼310°C: the shape of the nanostructure is round or triangular, and the face is not clear. At ∼340°C, the Cu nanostructures form preferentially at steps and domain boundaries of the substrate: the shape is triangular with truncated corners and the nanostructures have some facets. The top face has an inclination angle of ∼6° and the side face has one of ∼35°. On the top face, mono‐atomic steps can be seen ∼0.8 nm apart. From these results, it is concluded that the Cu nanostructure has a {554} facet on top and a {110} facet on the side. Copyright © 2003 John Wiley & Sons, Ltd.
Formation of promising Co–C nanocompositions
Authors: Lavrentiev V. , Abe H. , Yamamoto S. , Naramoto H. , Narumi K.
Published: January 2003

Encapsulation of Co nanoparticles ∼20 nm in size by C60‐based substances has been realized by simultaneous deposition of cobalt (electron beam evaporation) and C60 fullerene (thermal sublimation) on (0001) α‐Al2O3 and (001) NaCl substrates at room temperature under 10−5 Pa. Sharp hills 20 nm above the film surface were detected by atomic force microscopy and scanning electron microscopy. Electron diffraction analysis revealed the existence of diamond near distorted fcc Co crystals. Graphite, Co2C and Co3C carbides also have been found. Raman spectra confirm the appearance of diamond and graphite in an as‐deposited Co + C60 mixed film. The behaviour of the main Raman modes reflects the formation of Co–C60 polymeric chains during co‐deposition. Analysis of Raman spectra discovered a pronounced growth of diamond and single‐wall carbon nanotubes during annealing of the Co + C60 mixed film even at 300°C. The formation of these promising nanostructures is discussed. Copyright © 2003 John Wiley & Sons, Ltd.
Characterization of ultrathin InAs quantum wells by TEM–cathodoluminescence and TEM techniques
Authors: Grillo V. , Genseki A. , Yamamoto N. , Watanabe Y.
Published: January 2003

Emission from ultrathin quantum wells of different thicknesses is studied. In particular, for structures with doped substrate the unintentional deposition of Cu droplets is used as a probe of electron diffusion inside the material. A large diffusion length (L = 8 ± 3 µm) is found in spite of the presence of quantum dots. In particular, the contribution to the diffusion from re‐emission of electrons from quantum dots is evaluated. Copyright © 2003 John Wiley & Sons, Ltd.
Determination of 3D atomic structure of surfaces and interfaces by photoelectron holography
Authors: Nihei Yoshimasa
Published: January 2003

Electron spectroscopy currently is used not only for electronic state analysis but also for determining the structure of solid surfaces. Photoelectron diffraction is particularly suitable for examining the structure of solid surfaces and interfaces. Moreover, the combination of medium‐energy scanned‐angle photoelectron diffraction and photoelectron holography is a very appealing and effective method for the characterization of epitaxial thin films. This is because the two techniques are based on the use of the same data set—scanned‐angle photoelectron diffraction patterns—to provide different kinds of features.

Photoelectron diffraction in the energy region of x‐rays requires a higher angular resolution and a high‐power x‐ray source, especially in high‐performance measurement systems. A new type of instrument equipped with a multi‐energy high‐power x‐ray source and high angle‐resolving analyser has been developed. Application of this instrument to atomic‐level characterization of some kinds of nanomaterial systems is currently in progress. Copyright © 2003 John Wiley & Sons, Ltd.
Phase reconstruction with simultaneous correction of spherical and astigmatic aberrations by three‐dimensional Fourier filtering method
Authors: Kawasaki Tadahiro , Takai Yoshizo
Published: January 2003

A phase reconstruction technique in transmission electron microscopy (TEM), called the three‐dimensional Fourier filtering method (3D‐FFM), was extended to simultaneous correction of spherical aberration and twofold astigmatism. The effect of the aberration correction was confirmed experimentally for a wide spatial frequency range in the corrected through‐focus images of an amorphous thin film. As an application of this method, the surface structure of a gold nanoparticle was observed. The aberration‐free phase image clearly reconstructed the atomic missing‐row structure at the edge of the particle. Copyright © 2003 John Wiley & Sons, Ltd.
Aberration‐free images observed with TEM and STEM
Authors: Shimizu R.
Published: January 2003

A defocus image modulation processing (DIMP) technique was verified successfully with the JSPS (Japan Society for the Promotion of Science) Super Electron Microscope that was developed in a 5‐year (1996–2001) project called ‘Development of Super Electron Microscope in Next Generation’ under the JSPS Research for the Future programme (RFTF). This novel DIMP‐transmission electron microscope (DIMP‐TEM) is commercially available as the first phase‐contrast electron microscope. The DIMP‐TEM enables aberration‐free images of the selected phase contrast or amplitude contrast to be observed on cathode ray tubes in real time (2/30 s), leading to dynamic observation of events such as migration of a single atom on a surface as well as unstained biological specimens, where a low phase contrast is an inherent part of their images.

The situation regarding scanning transmission electron microscopes (STEMs) is more favourable from a technical point of view, although this has yet to be recognized. According to the reciprocity theorem, any aberration‐free imaging technique for TEMs should be, in principle, applicable to STEMs. A DIMP‐STEM would enable us to extract aberration‐free scan images observed with an ideal electron probe and obtained by an aberration‐free electron optical system.

This paper reviews recent advances in DIMP‐TEMs and presents a proposal for a novel DIMP‐STEM. Copyright © 2003 John Wiley & Sons, Ltd.
Evaluation of high‐precision phase‐shifting electron holography by using hologram simulation
Authors: Yamamoto Kazuo , Hirayama Tsukasa , Tanji Takayoshi , Hibino Michio
Published: January 2003

In phase‐shifting electron holography, Fresnel diffraction at an electron biprism introduces distortions to the amplitude and phase of the electron waves, which cause phase errors in the reconstructed phase images. To reduce the phase errors, two correction methods have been proposed, termed Fresnel corrections. In order to evaluate the phase‐shifting electron holography with Fresnel corrections, we faithfully simulated holograms by considering the influence of Fresnel diffraction, the quantum noise and the electron wave coherency, and then compared the phase images reconstructed from corrected and uncorrected holograms. We found that the phase error due to Fresnel diffraction was reduced to 1/20 by using Fresnel corrections, and that the phase measurement precision reached 2π/410 rad. We are able to observe the weak electric field due to positive charges corresponding to five electrons. Copyright © 2003 John Wiley & Sons, Ltd.
Real‐time observation of surface morphology at nanometer scale using x‐ray specular reflection
Authors: Kawamura T. , Watanabe Y. , Fujikawa S. , Bhunia S. , Uchida K. , Matsui J. , Kagoshima Y. , Tsusaka Y.
Published: January 2003

The changes of surface morphology at nanometer scale during metal–organic vapour‐phase epitaxial growth of indium phosphide have been investigated by using x‐ray specular reflection at grazing incidence. At the low growth temperature of 400°C, large decreases of x‐ray beam intensity were observed, suggesting the formation of nanometer‐sized nuclei. At a higher growth temperature of 500°C, oscillations estimated to by layer‐by‐layer growth were observed, and roughness changes obtained from these oscillations were <0.01 nm, suggesting small‐island formation on the terrace or step‐edge fluctuation during the growth. Additionally, reflectivity increases at a growth temperature of 550°C were observed. Considering the reflectivity dependence on t‐butylphosphine flow at 400°C, the change of reflectivity at 550°C is explained by the existence of phosphorus layers before the growth. Copyright © 2003 John Wiley & Sons, Ltd.
X‐ray reflection from thin multilayers: symmetric patterns
Authors: Karimov Pavel , Harada Shingo , Kawai Jun
Published: January 2003

A series of experiments on x‐ray reflection from thin multilayers and films on a silicon wafer were carried out. The x‐ray source and detector were fixed and the glancing angle was changed by sample stage rotation. The use of a Geiger‐Müller counter allowed bizarre symmetric patterns to be obtained in the reflected x‐ray intensity. The origin of these patterns is not clear at the present stage of the investigation.

To perform a preliminary analysis of the x‐ray reflection from multilayers, the Microsoft Access database has been developed. Copyright © 2003 John Wiley & Sons, Ltd.
Atomic structure of Si(113) surface studied by coaxial impact collision ion scattering spectroscopy
Authors: Kim K. S. , Choi J. U. , Cho Y. J. , Kang H. J.
Published: January 2003

The atomic structure of Si(113) has been studied by using time‐of‐flight coaxial impact collision ion scattering spectroscopy (ToF‐CAICISS) and reflection high‐energy electron diffraction (RHEED). The RHEED observations showed two ordered phases of 3 × 2 and 3 × 1. A phase transition of 3 × 2 to 3 × 1 was observed to occur reversibly in a temperature range of 450–550°C. From the CAICISS measurements, it was found that the intensity variations of the 3 × 2 phase are most probably consistent with the 3 × 1 phase and they are almost symmetric on [332], suggesting a geometrical similarity in the local atomic structure between the two reconstructions. It turned out that two reconstructions have top surface atoms with arrangement along [110], probably forming a unit of five atoms having a dimer as in previously reported structural models. The interatomic distance or bond length between the top surface atoms was determined. In particular, it was found that the dimer is positioned slightly lower than the other two top surface atoms. From these results, the atomic structure of Si(113) is discussed on the basis of previously reported structural models, including the unit of five atoms and the adatoms. Copyright © 2003 John Wiley & Sons, Ltd.
Monte Carlo study of the spin polarization enhancement in the low‐energy secondary electron emission from ferromagnetic materials
Authors: Yasuda Masaaki , Katsuse Ryuhei , Kawata Hiroaki , Murata Kenji
Published: January 2003

The spin polarization enhancement of secondary electrons emitted from ferromagnetic materials at low kinetic energies is studied by a Monte Carlo simulation of electron scattering that considers the spin direction of generated secondary electrons. A modified model of electron scattering in the magnetic materials is proposed that introduces electron–hole pair excitation processes with opposite spin (Stoner excitations). The two major characteristics—the primary energy dependence and the spectrum of secondary electron spin polarization—are studied with both the previous and the modified simulation models. A better agreement with experimental measurements is obtained in both characteristics with the modified model. The enhancement of the secondary spin polarization at low energies is reproduced by the introduction of Stoner excitation processes into the simulation. Copyright © 2003 John Wiley & Sons, Ltd.
Surface morphology and interface structural analyses of Ti(film)/SiC(substrate) by PEEM, SXES, AES and XRD
Authors: Labis Joselito , Ohi Akihiko , Hirai Masaaki , Kusaka Masahiko , Iwami Motohiro
Published: January 2003

A spectro‐microscopy study has been conducted on the Ti(film)/SiC(substrate) system. The variation in surface morphology of a heat‐treated Ti film on SiC was analysed by x‐ray photoemission electron microscopy (PEEM) and Auger electron spectroscopy (AES), whereas the interfacial reaction was characterized by synchrotron radiation‐induced soft x‐ray emission spectroscopy (SXES) and x‐ray diffraction (XRD). The formation of structures was observed on the Ti surface on 3C–SiC substrates at ∼850°C. The AES analysis on Ti/3C–SiC samples heated from 600°C to 900°C revealed an Si‐rich surface. The SXES and XRD characterizations on the structure of the interface have revealed the formation of Ti5Si3 and TiC as the dominant reaction products. Copyright © 2003 John Wiley & Sons, Ltd.
Imaging micropatterned organosilane self‐assembled monolayers on silicon by means of scanning electron microscopy and Kelvin probe force microscopy
Authors: Wu Yunying , Hayashi Kazuyuki , Saito Nagahiro , Sugimura Hiroyuki , Takai Osamu
Published: January 2003

Field‐emission scanning electron microscopy (FE‐SEM) and surface potentiometry based on scanning probe microscopy, i.e. Kelvin probe force microscopy (KFM), have been applied to study microstructures consisting of organosilane self‐assembled monolayers (SAMs) terminated with ‐CH3 or ‐CF3 groups. Onto cleaned Si substrates covered with a thin oxide layer of 2 nm thick, SAMs were formed by chemical vapour deposition using n‐octadecyltrimethoxysilane (CH3(CH2)17Si(OCH3)3, ODS) or fluoroalkylsilane (CF3(CF2)7(CH2)2Si(OCH3)3, FAS) as a precursor. Through a photolithographic technique employing vacuum ultraviolet light at 172 nm, microstructures composed of ODS, FAS or both were fabricated. Micropatterns of the SAMs on SiO2/Si substrates were clearly imaged by FE‐SEM at an acceleration voltage of the electron beam below 1 kV, but image contrasts became faint with an increase in the acceleration voltage. At a voltage of 5 kV there was almost no detectable contrast. An FE‐SEM image of the ODS–FAS microstructure acquired at an acceleration voltage of 0.8 kV clearly demonstrated that the region covered with ODS was brighter and thus, emitted secondary electrons more efficiently than the region covered with FAS. Furthermore, as indicated in a KFM image, the region covered with FAS had a surface potential ∼180 mV lower than that of the region covered with ODS. The origin of these image contrasts between ODS‐ and FAS‐SAMs was the large difference in electronic states between ODS and FAS owing to the electron negativity of fluorine atoms. Copyright © 2003 John Wiley & Sons, Ltd.
AFM observation of nanosized SiC dots prepared by ion beam deposition
Authors: Xu Y. , Narumi K. , Miyashita K. , Naramoto H.
Published: January 2003

Nanosized silicon carbide (SiC) dots are grown by low‐energy mass‐selected ion beam deposition (MSIBD) on 4°‐off Si(111) substrates at temperatures of 800–950°C and examined by atomic force microscopy (AFM). We find that the size distribution and the geometrical arrangement of SiC dots strongly depend on the substrate temperature, i.e. highly uniform SiC dots are formed at 800°C and 850°C; in particular, SiC dots are arranged in lines when the deposition temperature is as low as 800°C. These results indicate that self‐assembled SiC dots can be prepared on misoriented substrates at low deposition temperatures. Copyright © 2003 John Wiley & Sons, Ltd.
Ab initio molecular orbital calculation for hydrogen‐induced states of titanium (III)
Authors: Hayashi Kazuya , Nakagawa Sachiko T. , Mizuno Yoshiyuki , Tanaka Akihiro , Homma Teiichi
Published: January 2003

When titanium (Ti) metal absorbs a lot of hydrogen, the XPS spectrum shows a remarkable change in the valence band. Making use of molecular orbital (MO) calculations, we ascribed the peak shift to the formation of a hydrogen‐induced state of Ti. The trapped site of hydrogen in Ti may be at the lattice point in titanium hydride (TiH2), which forms a polycrystal with the small Ti crystals. Copyright © 2003 John Wiley & Sons, Ltd.
Distribution of lattice parameters in strain‐compensated MQW laser diodes
Authors: Seo Satoru , Matsuda Takeyoshi , Mitose Kengo , Iwase Fusako
Published: January 2003

We have developed a lattice image analysis method that gives lattice parameters directly from the lattice image of multiple quantum well (MQW) laser diodes, in order to judge whether the strain‐compensated structure is adopted or not. The method can handle a large amount of image data. The noise element in the lattice image is removed when the one‐dimensional Fourier transform is applied, and the lattice parameter value is obtained with good precision and good accuracy. The distribution of lattice parameters is valuable for evaluating the structure. Copyright © 2003 John Wiley & Sons, Ltd.
Coherent electron emission from carbon nanotubes: asymmetric young's interference fringes
Authors: Yamashita T. , Matsuda K. , Kona T. , Mogami Y. , Komaki M. , Murata Y. , Oshima C.
Published: January 2003

We have calculated the Young's interference of two electron beams that are asymmetrical about the emission current and/or emission area and compared them with the experimental results of field emission patterns from multi‐walled carbon nanotubes. Most of the fringes observed from the clean surface were similar to those produced with the symmetric slit system, which corresponds to the fact that asymmetry in intensity does not change the fringe shape. In addition, no interference fringes of the two asymmetrical beams about the area were detected. Molecular chemisorption enhanced the emission current at an emission site, but the electron waves were incoherent to the others. Copyright © 2003 John Wiley & Sons, Ltd.
Structural characterization of C60 nanowhiskers formed by the liquid/liquid interfacial precipitation method
Authors: Miyazawa K. , Kuwasaki Y. , Hamamoto K. , Nagata S. , Obayashi A. , Kuwabara M.
Published: January 2003

The structure of C60 whiskers fabricated by using the liquid/liquid interfacial precipitation method is analysed with transmission electron microscopy (TEM). The C60 whiskers with submicrometre diameters, named ‘C60 nanowhiskers (C60NWs)’, contain (002)c planar faults, and the centre‐to‐centre distance between the C60 molecules along the growth axis of C60NWs is shortened ∼1% compared with that of pristine C60 crystals, indicating the formation of chemical bondings between the C60 molecules along [110]c ([100]t) close‐packed directions of the C60NWs. The electrical resistivity of C60 whiskers decreased on decreasing their diameter. This result suggests that the C60NWs are electrically conductive. The C60 whiskers are very flexible and could form a semicircle with a curvature radius of 38 µm. Copyright © 2003 John Wiley & Sons, Ltd.
Marginal versus joint Box–Cox transformation with applications to percentile curve construction for IgG subclasses and blood pressures
Authors: He Xuming , Ng K. W. , Shi Jian
Published: January 2003

When age‐specific percentile curves are constructed for several correlated variables, the marginal method of handling one variable at a time has typically been used. We address the question, frequently asked by practitioners, of whether we can achieve efficiency gains by joint estimation. We focus on a simple but common method of Box–Cox transformation and assess the statistical impact of a joint transformation to multivariate normality on the percentile curve estimation for correlated variables. We find that there is little gain from the joint transformation for estimating percentiles around the median but a noticeable reduction in variances is possible for estimating extreme percentiles that are usually of main interest in medical and biological applications. Our study is motivated by problems in constructing percentile charts for IgG subclasses of children and for blood pressures in adult populations, both of which are discussed in the paper as examples, and yet our general findings are applicable to a wide range of other problems. Copyright © 2003 John Wiley & Sons, Ltd.
Viral load detectability profiles for HIV infection
Authors: McKinnon Elizabeth J. , James Ian R. , John Mina , Mallal Simon A.
Published: January 2003

The introduction of potent antiretroviral therapies for treatment of HIV infection typically results in a dramatic reduction in plasma HIV RNA concentration, often to levels undetectable by current measurement practices. However, although a high proportion of patients achieve ‘undetectability’, many then experience a return to a state of detectability at a later date. As evaluation of virologic response provides a useful measure of therapy efficacy, it is of interest to estimate the proportions of cases with undetectable viral load over time following commencement of treatment. These proportions depend on the rates of transition from detectability to undetectability and subsequent return to detectability, and may be related to covariates or risk factors, possibly differing in both transitions. We consider construction of detectability profiles as estimates of these proportions, based on parametric modelling of the component survival distributions. The method is applied to an examination of the effects of baseline CD4 T‐cell lymphocyte counts on virologic response to therapy amongst patients of the Western Australian HIV Cohort Study. Copyright © 2003 John Wiley & Sons, Ltd.
Inference for a linear regression model with an interval‐censored covariate
Authors: Gómez Guadalupe , Espinal Anna , W. Lagakos Stephen
Published: January 2003

Interval‐censored observations of a response variable are a common occurrence in medical studies, and usually result when the response is the elapsed time until some event whose occurrence is periodically monitored. In this paper we consider a multivariate regression setting in which the explanatory variable is interval censored. Use of anad hocmethod of analysis for such data, such as taking the midpoint of the interval‐censored covariate and applying ordinary least‐squares, is not in general valid. We develop a likelihood approach, together with a two‐step conditional algorithm, to jointly estimate the regression coefficients as well as the marginal distribution of the covariate. The resulting estimators are asymptotically normal. The performance of the method is assessed via simulations, and illustrated using data from a recent HIV/AIDS clinical trial to assess the association between waiting time between indinavir failure and subsequent viral load at enrolment. Extensions of the procedure to other parametric distributions are discussed. Copyright © 2003 John Wiley & Sons, Ltd.
Estimating cumulative probabilities from incomplete longitudinal binary responses with application to HIV vaccine trials
Authors: Hudgens Michael G.
Published: January 2003

When describing longitudinal binary response data, it may be desirable to estimate the cumulative probability of at least one positive response by some time point. For example, in phase I and II human immunodeficiency virus (HIV) vaccine trials, investigators are often interested in the probability of at least one vaccine‐induced CD8+ cytotoxic T‐lymphocyte (CTL) response to HIV proteins at different times over the course of the trial. In this setting, traditional estimates of the cumulative probabilities have been based on observed proportions. We show that if the missing data mechanism is ignorable, the traditional estimator of the cumulative success probabilities is biased and tends to underestimate a candidate vaccine's ability to induce CTL responses. As an alternative, we propose applying standard optimization techniques to obtain maximum likelihood estimates of the response profiles and, in turn, the cumulative probabilities of interest. Comparisons of the empirical and maximum likelihood estimates are investigated using data from simulations and HIV vaccine trials. We conclude that maximum likelihood offers a more accurate method of estimation, which is especially important in the HIV vaccine setting as cumulative CTL responses will likely be used as a key criterion for large scale efficacy trial qualification. Copyright © 2003 John Wiley & Sons, Ltd.
Incremental net benefit in randomized clinical trials with quality‐adjusted survival
Authors: Willan Andrew R. , Bingshu Chen Eric , Cook Richard J. , Lin D. Y.
Published: January 2003

Owing to induced dependent censoring, estimating mean costs and quality‐adjusted survival in a cost‐effectiveness comparison of two groups using standard life‐table methods leads to biased results. In this paper we propose methods for estimating the difference in mean costs and the difference in mean effectiveness, together with their respective variances and covariance in the presence of dependent censoring. We consider the situation in which the measure of effectiveness is either the probability of surviving a duration of interest or mean quality‐adjusted survival time over a duration of interest. The methods are illustrated in an example using an incremental net benefit analysis. Copyright © 2003 John Wiley & Sons, Ltd.
A parametric model for long‐term follow‐up data from phase III breast cancer clinical trials
Authors: Jeong Jong‐Hyeon , Jung Sin‐Ho , Wieand Samuel
Published: January 2003

We propose a parametric version of a univariate gamma frailty model. The proposed model is shown to be flexible enough to model long‐term follow‐up survival data from breast cancer clinical trials when the treatment effect diminishes as time progresses, a case for which neither the proportional hazards nor proportional odds assumptions are satisfied. The observed information matrix is computed to evaluate the variances of parameter estimates. A simple parametric test statistic to test proportional odds assumption is also constructed. The model is applied to a data set from a phase III clinical trial on breast cancer. Copyright © 2003 John Wiley & Sons, Ltd.
A statistical perspective on gene expression data analysis
Authors: Satagopan Jaya M. , Panageas Katherine S.
Published: January 2003

Rapid advances in biotechnology have resulted in an increasing interest in the use of oligonucleotide and spotted cDNA gene expression microarrays for medical research. These arrays are being widely used to understand the underlying genetic structure of various diseases, with the ultimate goal to provide better diagnosis, prevention and cure. This technology allows for measurement of expression levels from several thousands of genes simultaneously, thus resulting in an enormous amount of data. The role of the statistician is critical to the successful design of gene expression studies, and the analysis and interpretation of the resulting voluminous data. This paper discusses hypotheses common to gene expression studies, and describes some of the statistical methods suitable for addressing these hypotheses. S‐plus and SAS codes to perform the statistical methods are provided. Gene expression data from an unpublished oncologic study is used to illustrate these methods. Copyright © 2003 John Wiley & Sons, Ltd.
Non‐linear models for the relation between cardiovascular risk factors and intake of wine, beer and spirits
Authors: Ambler Gareth , Royston Patrick , Head Jenny
Published: January 2003

It is generally accepted that moderate consumption of alcohol is associated with a reduced risk of coronary heart disease (CHD). It is not clear however whether this benefit is derived through the consumption of a specific beverage type, for example, wine. In this paper the associations between known CHD risk factors and different beverage types are investigated using a novel approach with non‐linear modelling. Two types of model are proposed which are designed to detect differential effects of beverage type. These may be viewed as extensions of Box and Tidwell's power‐linear model. The risk factors high density lipoprotein cholesterol, fibrinogen and systolic blood pressure are considered using data from a large longitudinal study of British civil servants (Whitehall II). The results for males suggest that gram for gram of alcohol, the effect of wine differs from that of beer and spirits, particularly for systolic blood pressure. In particular increasing wine consumption is associated with slightly more favourable levels of all three risk factors studied. For females there is evidence of a differential relationship only for systolic blood pressure. These findings are tentative but suggest that further research is required to clarify the similarities and differences between the results for males and females and to establish whether either of the models is the more appropriate. However, having clarified these issues, the apparent benefit of consuming wine instead of other alcoholic beverages may be relatively small. Copyright © 2003 John Wiley & Sons, Ltd.
Financial strategy at YPF
Authors: Grosse Robert
Published: January 2003

Yacimientos Petroliferos Fiscales (YPF) was formerly state‐owned and the largest company in
Argentina in 1995. It was privatized in 1993, and was planning its second annual capital budget as a
private‐sector company in the fall of 1994. When the Tequila Crisis hit Mexico in December of 1994,
international borrowing became much more difficult for emerging market borrowers in general and Argentine
borrowers in particular. This case presents the situation that faced YPF at the beginning of 1995, after most of
the pieces of its capital budget had been laid out but not finalized at the end of 1994.
Implications of the introduction of the Euro for the Mediterranean countries
Authors: Colton Nora , Neaime Simon
Published: January 2003

The Mediterranean peripheral countries cannot afford to be passive viewers of the fundamental changes that are
taking place in Europe after the introduction of the Euro. The new developments pose formidable challenges and
opportunities. It will be argued that no single group of developing countries will be more affected by these
changes than the Mediterranean countries given their geographical proximity to the region and their long
historical record of extensive and large economic interactions (trade, finance, and migration). This
article examines the implications of the introduction of the single currency in Europe on Mediterranean central
bank reserves and foreign external liabilities, trade and capital flow, and exchange rate policies. It is shown
that since most Mediterranean trade is with the EU, Mediterranean central banks will be necessitated to hold major
portions of their foreign exchange reserves in Euros. Also, a Mediterranean currency peg to the Euro, or to a
basket of currencies where the Euro is allocated, will be important in reducing financial and trade transaction
costs. It will also be hypothesized that Mediterranean foreign debts will eventually have to be converted to
Euros. Finally, parallels between this region and the U.S–Caribbean region will be drawn to reinforce the
argument that trade and capital dependence will eventually lead to a pegging of the Mediterranean currencies to
the Euro. © 2003 Wiley Periodicals, Inc.
Soft vs. hard approach in communicating on corporate social responsibility
Authors: Tixier Maud
Published: January 2003

These past years, companies have become aware that their mission went beyond mere profit‐making. Corporate social responsibility toward all stakeholders is today, more than ever, an important stake for communication. Companies must know how to communicate if a social or environmental crisis occurs. However, effective communication must be based on facts. Management must consider a new criterion for success: the ability to respond to all the actions of the company, at all levels.

Faced with widespread confusion regarding what is conventionally referred to as “corporate social responsibility” and regarding all matters related to the subject, which may or may not be the result of a trend, we opt for a straightforward and practical approach by focusing on one question: Should there be more talk of the social duties of companies, and if so, how are we to tackle the issue?

We have observed that there are many conflicting opinions on the matter, at least in certain countries, including France. This raises points hardly spoken of in the numerous works broaching the subject. Opinions may be based on differing attitudes on legitimacy (do companies have an obligation to their community besides being formed to make a profit?), on the legislation provided by countries on “corporate citizenship” (laws of the home and host countries), on the expectations of the society in which the firm exists, and on the logic of those putting forth those opinions. © 2003 Wiley Periodicals, Inc.
World investment report 2001: Promoting linkages
Authors: Wymbs Cliff
Published: January 2003

United Nations Conference on Trade and Development (UNCTAD). 2001. World Investment Report
2001: Promoting Linkages. New York and Geneva:United Nations. 384 pages. ISBN:
92‐1‐112523‐5.
Declining global market share of Singapore's electronics exports: Is it a concern?
Authors: Wu Friedrich , Loy Chua Boon
Published: January 2003

In contrast with the steadily rising shares of other regional exporters, Singapore's export shares in
the global electronics market have been faltering in recent years. This has given rise to concerns about its
export competitiveness. The drop in Singapore's global ranking can be attributed to shrinking exports of
end products and low‐end electronics parts, as manufacturers relocate such assembly production out of
Singapore to the regional economies. Fortunately, Singapore remains competitive in the export of
high‐end intermediate electronics components, which are characterized by capability, technology, and
automation‐intensive processes. While Singapore is progressing in the right direction, the climb up the
high‐tech value chain needs to be further accelerated in order to maintain a technology gap with
regional exporters. Besides accelerating its own industrial upgrading, Singapore needs to actively pursue
measures that would help create a more integrated and competitive production platform for ASEAN, as well as to
seek opportunities to service the rapidly enlarging consumer market in China. © 2003 Wiley Periodicals,
Inc.