bluuebunny/crossref_metadata_2025 huggingface dataset:
Treatment of Immobilized Collagen on Poly(tetrafluoroethylene) Nanoporous Membrane with Plasma
Authors: Bratescu Maria Antoaneta , Saito Nagahiro , Takai Osamu
Published: October 2006

In this work we treated type I collagen immobilized on different nanoporous membranes with microwave (MW) argon plasma. Hydrophobic and hydrophilic nanoporous substrates of poly(tetrafluoroethylene), with thickness varying from 35 to 70 µm and a 100 nm pore size, were employed as support for collagen immobilization. On the hydrophilic nanoporous membrane, after the MW plasma treatment, the immobilized collagen changed its morphology and showed a tendency to self-assemble in quasi-regular forms as microellipsoids. The presence of collagen immobilized on the nanoporous membrane after the MW plasma treatment was analyzed by detecting in the Raman spectrum an α-helix form, NH deformation vibration, amide II band at 1550 cm-1, a characteristic group frequency of the collagen macromolecule.
Sterilization of Medical Equipment Using Radicals Produced by Oxygen/Water Vapor RF Plasma
Authors: Hayashi Nobuya , Guan Weimin , Tsutsui Shinsuke , Tomari Tetsushi , Hanada Yasushi
Published: October 2006

The sterilization of medical equipment was performed using low-pressure RF discharge plasma. Oxygen radicals as oxidizing materials for sterilization were produced from oxygen or water vapor. The generation of atomic oxygen and OH radicals was confirmed using the light emission spectra of the plasma. The pressure in the discharge region was varied periodically during inactivation in order to produce radicals effectively and to penetrate the produced radicals into tiny gaps. Medium sheets for microbial detection indicated that the decimal reduction value of active bacillus was 5 and 8 min using oxygen plasma and water vapor plasma with n
e=109 cm-3, respectively. Biological indicators clarified that the sterilization of bacilli spores was successful for a treatment time of 90 min.
Effects of Thermal Annealing for Restoration of UV Irradiation Damage during Plasma Etching Processes
Authors: Ichihashi Yoshinari , Ishikawa Yasushi , Kato Yuji , Shimizu Ryu , Okigawa Mitsuru , Samukawa Seiji
Published: October 2006

During plasma etching processes, UV and vacuum ultraviolet (VUV) photon irradiation generates defects and causes an increase in interface state density between SiO2 and Si. To understand the effects of pulse-time-modulated plasma on reducing damage, defects in a SiO2 film (E' center) after etching processes were measured using the electron spin resonance (ESR) method. We found that the density of the E' center was markedly reduced using C4F8/O2 pulse-time-modulated (TM) plasma etching, as compared with continuous wave (CW) plasma etching. This corresponds to the changes in interface state density using the charge pumping method. Conversely, in both cases, these E' centers were almost eliminated by H2/N2 annealing at 400 °C. Interface state density, however, remained constant even by annealing in both cases, whereas, interface state density when using TM plasma was much smaller than that when using CW plasma. This result suggests that H2/N2 annealing is not sufficient to restore the interface state density between SiO2 and Si. To reduce the increase in interface state density, UV irradiation damage must first be suppressed during plasma etching. Consequently, a combination of TM plasma etching and thermal annealing is very effective for reducing UV irradiation damage to achieve high reliability in metal–insulator–silicon (MIS) devices.
Structural Characterization of Polycrystalline 3C–SiC Films Prepared at High Rates by Atmospheric Pressure Plasma Chemical Vapor Deposition Using Monomethylsilane
Authors: Kakiuchi Hiroaki , Ohmi Hiromasa , Nakamura Ryota , Aketa Masatoshi , Yasutake Kiyoshi
Published: October 2006

Polycrystalline cubic silicon carbide (3C–SiC) films were deposited at a relatively low temperature of 1070 K on Si(001) substrates by atmospheric pressure plasma chemical vapor deposition. Monomethylsilane (CH3SiH3) was used as the single source. CH4 and SiH4 dual sources were also used to compare deposition characteristics. Under the present deposition conditions, very high deposition rates of more than 3 nm/s were obtained. The structure of the SiC films was evaluated by reflection high-energy electron diffraction, Fourier transform infrared absorption spectroscopy and cross-sectional transmission electron microscopy. In addition, optical emission spectroscopy was employed to study the chemical reactions in the CH4/SiH4 and CH3SiH3 plasmas. The results showed that increasing H2 concentration is essential in forming a high quality 3C–SiC film by enhancing the hydrogen elimination reaction at the film-growing surface. From the optical emission spectra, it was found that atomic hydrogen generated by adding H2 in the plasma increase the amount of principal precursors for the film growth. The utilization of CH3SiH3 also led to a higher concentration of principal precursors in the plasma, enhancing the incorporation of Si–C bonds into the film. As a consequence of simultaneously using a high H2 concentration and the CH3SiH3 single source, the columnar growth of 3C–SiC crystallites was achieved.
NO Sensing Property of Carbon Nanotube Based Thin Film Gas Sensors Prepared by Chemical Vapor Deposition Techniques
Authors: Ueda Tsuyoshi , Norimatsu Hideyuki , Bhuiyan Md. Mosharraf Hossain , Ikegami Tomoaki , Ebihara Kenji
Published: October 2006

To prepare a gas sensor that can operate at room temperature, carbon nanotubes (CNTs) were grown on Al2O3 substrates with interdigital Pt electrodes (Al2O3 substrate) by both pulsed laser deposition (PLD) and chemical vapor deposition (CVD). In this combined method, Fe catalytic thin film was prepared by PLD and then CNTs were grown on the Fe thin film by thermal CVD using an ethylene gas. The surface images of the prepared CNTs on the substrates were observed by scanning electron microscopy (SEM), and the sensitivity to NO gas was measured. The resistance of the prepared CNT-based gas sensor was found to decrease with increasing sensor temperature, and it decreased with increasing NO gas concentration at room temperature. In this paper, it is suggested that CNT gas sensors have a great possibility to be applied as innovative NO gas sensors on the basis of the experimental results.
Comparative Study on Chemical Vapor Deposition of Diamond-Like Carbon Films from Methane and Acetylene Using RF Plasma
Authors: Hassan Md. Kamrul , Pramanik Bimal Kumar , Hatta Akimitsu
Published: October 2006

Diamond-like carbon films (DLC) were prepared by radio-frequency plasma-enhanced chemical vapor deposition (RF-PECVD) at a frequency of 13.56 MHz using methane (CH4) and acetylene (C2H2) at different RF powers. Optical emission spectroscopy (OES) was carried out to investigate plasma chemistry. The intensity of Hα in the C2H2 plasma was about one-half that in the CH4 plasma, whereas in both cases, the intensities of CH radicals were similar. The resistivity of the deposited films decreased with an increase in RF power, whereas growth rate increased with RF power. CH4-based films were found to be more insulating than C2H2-based films at high RF powers. The high resistivity of the films was obtained from both CH4 and C2H2 at low RF powers. The insulating property was due to the hydrogenation of sp2 bonds in the films.
Effects of Plasma Power and Plasma Sheath on Field Emission Properties of Carbon Nanotubes
Authors: Ting Jyh-Hua , Su Chin-Yan , Huang Fuang-Yuan , Hsu Cho-Lun , Samukawa Seiji
Published: October 2006

With a nickel catalyst, carbon nanotubes (CNTs) were prepared by microwave plasma-enhanced chemical vapor deposition (MPCVD). Transmission electron microscopy (TEM) images reveal the center hollowness and multiwall structure of CNTs. The tip-growth mechanism of the CNTs prepared by MPCVD is confirmed by the Ni particles enclosed at the tips of the CNTs. The degree of CNT graphitization increases with plasma power up to about 1000 W and then reaches the upper limit. This is attributed to an insufficient carbon feedstock for CNT growth. The field emission (FE) efficiency of the CNTs increases with plasma power. For plasma powers not greater than 1000 W, the increase in graphitization degree and the decrease in the number of defects in a CNT emitter array enhance FE performance. The defects produced by the large split catalysts remaining in the CNTs at low plasma powers (700 and 800 W) also result in a low FE efficiency. Although the CNTs grown at moderate to high plasma powers (1000 to 1200 W) have similar graphitization degrees, a low plasma power results in split catalysts and hence defects, as evidenced by TEM observation. These defects accumulate electrons, block electronic transport, and hence reduce the FE efficiency of the CNTs. The effect of kinked CNTs produced by the a plasma sheath on FE efficiency is negligible.
Electron Spectroscopy of COx Magnetron Sputtered Films
Authors: Zemek J. , Bohac P. , Kulikovsky V.
Published: October 2006

CO
x
films were deposited by magnetron sputtering of a graphite target within two different routes: (i) by sputtering in an Ar+O2 gas mixture or (ii) by sputtering in pure Ar followed by annealing at 300 °C in air. Surface composition and chemical bonding was studied by X-ray induced photoelectron and Auger electron spectroscopy (XPS/XAES), and electron energy loss spectroscopy (EELS) in a low energy loss region. Oxygen content reached ∼20 at. % in the CO
x
layers, independent on the route used. The C 1s spectral line shapes indicate C–O and C=O bonding states, regardless dominating C–C and CH
x
bonds. Substantial differences were found in the XAES and reflection electron energy loss spectra (REELS) recorded from surface regions of the samples. The both spectra indicate dominating sp2 bonding of carbon atoms in an analyzed volume of CO
x
films sputtered in Ar and oxidized in air at elevated temperature whereas for those deposited in an Ar+O2 mixture the sp3 bonding prevails over sp2.
Low-Temperature Growth of Epitaxial Si Films by Atmospheric Pressure Plasma Chemical Vapor Deposition Using Porous Carbon Electrode
Authors: Ohmi Hiromasa , Kakiuchi Hiroaki , Tawara Naotaka , Wakamiya Takuya , Shimura Takayoshi , Watanabe Heiji , Yasutake Kiyoshi
Published: October 2006

The low-temperature growth of epitaxial Si films by atmospheric pressure plasma chemical vapor deposition (AP-PCVD) was investigated. A 150 MHz very high frequency (VHF) power supply was used to generate an atmospheric pressure plasma of gas mixtures containing He, H2, and SiH4. Two types of electrode (i.e., cylindrical rotary and porous carbon electrodes) were used in plasma generation. When a cylindrical rotary electrode was used, polycrystalline Si growth was inevitable at the film edge on the upstream side. This is due to the variation in deposition rate along the gas flow direction, which is extremely high at the plasma/atmosphere interface on the upstream side. To solve this problem, we developed a novel porous carbon electrode where process gas molecules are directly supplied into the plasma region through a porous carbon plate a distance (0.8 mm) away from the substrate surface. Using such a porous carbon electrode, we successfully grew a defect-free epitaxial Si film on the entire surface of a 4 in. Si wafer at 600 °C. The average growth rate was 0.25–0.3 µm/min, which is as high as that obtained by thermal CVD at 900 °C. The epitaxial Si films grown at 600 °C were characterized by various methods, including transmission electron microscopy, atomic force microscopy, secondary ion mass spectrometry, and selective etching. The influence of adsorbed impurities in the porous carbon material on the quality of epitaxial Si films was also investigated.
Characteristics of a Multilayer SiOx(CH)yNz Film Deposited by Low Temperature Plasma Enhanced Chemical Vapor Deposition Using Hexamethyldisilazane/Ar/N2O
Authors: Lee June Hee , Jeong Chang Hyun , Lim Jong Tae , Zavaleyev Viktor A. , Kyung Se Jin , Yeom Geun Young
Published: October 2006

SiO
x
(CH)
y
N
z
films were deposited at room temperature using plasma enhanced chemical vapor deposition (PECVD) with a gas mixture of hexamethyldisilazane [HMDS, Si2NH(CH3)6]/Ar/N2O. The characteristics of those films with increasing N2O were investigated. When no N2O was used, the film showed organic characteristics with a Si/O composition ratio of 2 and a large concentration of –CH
x
and N–H in the deposited film. However, with increasing N2O flow rate, oxygen-rich and transparent SiO2-like inorganic thin films could be obtained with a Si/O composition ratio of 0.5 and a lower –CH
x
and N–H in the deposited film. By turning on-and-off the N2O gas flow during SiO
x
(CH)
y
N
z
deposition, a multi-layer thin film consisting of an organic Si(CH)
x
-like film/inorganic SiO2-like thin film, which can be applied to the thin film passivation for organic devices could be successfully deposited.
Gas Sensing Properties of Metal Doped WO3 Thin Film Sensors Prepared by Pulsed Laser Deposition and DC Sputtering Process
Authors: Bhuiyan Md. Mosharraf Hossain , Ueda Tsuyoshi , Ikegami Tomoaki , Ebihara Kenji
Published: October 2006

Tungsten trioxide (WO3) thin films gas sensors were prepared by the KrF excimer pulsed laser deposition (PLD) method. The films were prepared on the quartz glass, silicon and also on the Al2O3 sensor substrates with platinum interdigitated electrodes. The effect of doping of the platinum (Pt), palladium (Pd) or gold (Au) on the WO3 thin film was also investigated. These metals were doped to the WO3 thin film by the DC sputtering process during the PLD. The substrate temperature and the oxygen pressure were 400 °C and 100 mTorr, respectively, during the deposition. The films were characterized by atomic force microscopy (AFM) and X-ray diffraction (XRD). The sensitivity of the prepared sensors to 60 ppm NO gas was examined using the two terminal resistance method in a chamber at atmospheric pressure and operating temperatures of 25–350 °C. The sensitivity of the WO3 thin films doped with Pt, Pd, or Au was found to be higher than that of the undoped WO3 thin film.
Preliminary Evaluation of Mass Attachment Effect of Ceramic Resonator Device Using Plasma Polymerized Styrene Film Deposition Method
Authors: Aizawa Hidenobu , Kurosawa Shigeru
Published: October 2006

The resonant properties of ceramic resonator device (CRD) coated with plasma-polymerized styrene film (PPSF) during mass loading were examined and compared with those of a quartz crystal microbalance (QCM) device. We tested three 4-MHz CRDs and two 9-MHz QCMs as a reference for PPSF. They were coated experimentally under several plasma-polymerization conditions (100 W of RF power at 13.56 MHz, 100 Pa of monomer pressure). The resonant properties of both devices were measured using an impedance analyzer. The resonance frequency shift is proportional to polymerization time until 240 min (ΔF
r=C
CRD
t,C=360 Hz/min for CRD, and ΔF
r=C
QCM
t,C
QCM=2448 Hz/min for QCM, respectively). The shift of resonance frequency for CRD is 7.13 ng/Hz. The PPSF-coated CRD showed a lower frequency shift than QCM for mass loading (about 0.14). Shifts of the resistance and Q-value during mass loading were not found on the CR, but they were found on the QCM. Those results imply that the low Q-value property of CR causes a small resistance shift for mass loading. The PPSF deposition method is suggested as a preliminary standardization of evaluation of the mass loading effect of CRD for applications of chemical sensors and biosensors under a high mass-loading condition.
Surface Modification of Narra Wood (Pterocarpus indicus) by Ion Shower Treatment
Authors: Blantocas Gene Q. , Ramos Henry J. , Wada Motoi
Published: October 2006

A gas discharge ion source (GDIS) was used as test facility to produce and study the characteristics of diffused, low-energy hydrogen ion showers. Narra wood samples were then exposed to the showers to investigate topographical effects of ion irradiation. Analysis of beam constituents by mass spectroscopy shows H+ ions to be the dominant species suggesting an essential participatory role for this particular monatomic ion in the surface modification process. Low energy irradiation (600–700 eV) produced hydrophobic surfaces with scanning electron micrographs showing partial closure of surface pores. Whereas, a reversion to hydrophilicity was observed for higher energy irradiation (>900 eV), with surface images showing exterior degradation believed to be the etching effects of the chemically active H+ species. The irradiated samples absorbency was quantified via the wetting model wherein the contact angle's time rate equation was numerically solved and fitted onto experimental data. The change rate proportionality constant K with value 0.0015 corresponding to 600 eV beam energy, exhibited the longest moisture absorptive inhibition time of more than 10 min. An increasing value of K indicates increased wetting behavior.
Effect of Surface and Growth Conditions for Formation of Textured Polycrystalline GaN Crystals by Reactive N2 Plasma
Authors: Flauta Randolph E. , Jr. Magdaleno R. Vasquez, , Ramos Henry J. , Wada Motoi
Published: October 2006

The surface and growth conditions for the formation of textured polycrystalline bulk gallium nitride (GaN) crystals under nitrogen (N2) reactive plasma were investigated. Langmuir probe measurements were used to determine the electron density values near the Ga surface at different target locations and ranged from (6–16)×1010/cm2. Optical spectroscopy measurements showed reactive gallium (Ga) and nitrogen species present in the plasma. When the target was bombarded with highly energetic ions, peaks of sputtered Ga at 403 and 417 nm wavelengths were observed in the optical spectroscopy measurements. The top Ga surface showed increased roughening and the resulting crystals were of poor crystalline quality, with fresh Ga leftovers. Smoother crystals were formed when the Ga target was shielded from the direct bombardment of highly energetic N2 plasma, with no sputtered Ga peaks observed during the bombardment. X-ray diffraction (XRD) analysis results revealed well-oriented crystals at the (0002) reflection of GaN. This proved that the shielding of highly energetic ions to decrease roughening of the surface and allowing more neutrals for the reaction were effective in forming well-oriented bulk GaN crystals.
Plasma Surface Treatment of Carbonaceous Materials for Application in Electric Double Layer Capacitors
Authors: Tashima Daisuke , Kurosawatsu Kenji , Uota Masafumi , Karashima Takeshi , Sung Youl-Moon , Otsubo Masahisa , Honda Chikahisa
Published: October 2006

In this work, carbonaceous materials were modified in order to improve capacitance and charge density in electric double layer capacitors (EDLCs). Optimal conditions for plasma surface treatment of activated carbon have been examined for times from 1 to 10 h at 150 °C. The plasma is a high-frequency glow discharge in N2. The pressure of the gas is 13.3 Pa. The electrode is set up so that the EDLC sample is covered with the glow discharge. Specific capacitance and charge density can be improved by plasma surface treatment of carbon materials.
An Investigation as to the Cause of Beam Asymmetry in a Compact Gas Discharge Ion Source: A Focus on Beam-Wall Interaction
Authors: Blantocas Gene Q. , Ramos Henry J. , Wada Motoi
Published: October 2006

Helium beams in a compact gas discharge source lose their transverse symmetry when the extracting electrode is biased at high potentials. Further, this condition gives rise to excessive formation of electrons within the vicinity of the beam line of propagation. A plausible explanation for these abnormalities is explained via the effects of the source extractor's lens property on the beams' physical configuration. The optical relation of the extractor shows that when the extraction voltage (V
e) exceeds half the discharge voltage (V
d), its focal length extends backward pass the discharge region's emitting orifice. As a consequence, beam divergence is increased akin to light beams expanding when the source is positioned between a negative lens and its principal focus. Numerical simulations of the beams' envelopes at different discharge and biasing conditions provide further proof of the theory's validity. When V
e>V
d/2, the construct shows exiting beams to have waists greater than the diameter of the drift tube suggesting increased interaction between beam edge and the tube's interior walls resulting in secondary electron emissions. The presence of electrons inexorably leads to charge neutralization thus creating asymmetric beams downstream. Mass spectroscopic detection of O- ions most likely from surface oxides, and increased electron densities obtained by way of Langmuir measurements are phenomenological evidences to this effect. This work intends to establish the explicit causality relation between secondary electron emission and the formation of asymmetric beams in miniaturized ion sources.
Textural and chemical zonation of pyrite at Pajingo: a potential vector to epithermal gold veins
Authors: Baker T. , Mustard R. , Brown V. , Pearson N. , Stanley C.R. , Radford N.W. , Butler I.
Published: October 2006

The Carboniferous Pajingo Epithermal System (PES) comprises several low sulphidation Au–Ag ore zones that have a total resource of
c
. 3 Moz (million ounces). The main Vera–Nancy vein is hosted by andesite that contains alteration which zones from inner silica–pyrite to argillic to distal propylitic alteration. Pyrite is ubiquitous in both alteration and vein. In the latter, pyrite is a minor component (<1%), but the dominant sulphide, and occurs as fine-grained (<50 μm) bands or disseminations. Coarse (up to 0.5 mm) euhedral pyrite is most abundant (up to 10%) in the silica–pyrite alteration whereas in argillic alteration pyrite (<50 to 250 μm) occurs as round to subhedral forms either as infill in narrow veinlets or as replacement. Fine-grained (<50 μm) pyrite occurs in propylitic alteration along rims of earlier mafic phenocrysts and has a low abundance (<1%). In-situ laser ablation inductively coupled plasma mass spectrometry was carried out on the pyrite in order to test the chemical variations between pyrite in different alteration zones. Results indicate that Mo and Ag concentrations vary over two orders of magnitude from the outer alteration zones (Mo
c
. 0.1 ppm; Ag
c
. 0.5 ppm) to the proximal vein alteration (Mo
c
. 30 ppm; Ag
c
. 20 ppm) whereas Pb displays an overall decrease from the hanging wall (a few hundred ppm) to the footwall (<100 ppm). Pyrite in the hanging- wall argillic alteration zone has Pb/Mo and Pb/Ag ratios of >100 whereas pyrite in silica–pyrite alteration zones has ratios of <100, and pyrite in silica–pyrite alteration zones immediately adjacent to the vein has Pb/Mo ratios of <30 and Pb/Ag ratios of <10. Thus, Pb/Mo and Pb/Ag ratios may provide a potentially powerful vector to epithermal gold veins in the PES and elsewhere.
Multi-element association analysis of stream sediment geochemistry data for predicting gold deposits in south-central Yunnan Province, China
Authors: Ali Khaled , Cheng Qiuming , Li Wenchang , Chen Yongqing
Published: October 2006

The use of traditional statistical and new methods of spatial analysis can provide suitable indicators of geochemical element dispersion, and aid in targeting potential areas for mineral exploration. A case study involving the analysis of stream sediment geochemistry data from an area in Yunnan province, South China, is presented. The area has two known areas of gold deposits where several mines are present. The study starts with an appraisal of the descriptive statistics of the data. Geological studies were conducted in the study area to obtain a thorough understanding of the regional geology, ore geology of known gold deposits, and mineralization, and to determine the mineral deposit model. Most of the GIS analysis was done using the stream sediment geochemical data. An inverse distance weighting interpolation algorithm was used to convert the point data to continuous surface (grid) maps for each element. Principal component analysis (PCA) was used to compress the information to a few maps and to assist in determining multi-element associations. The study revealed that most of the high element concentrations in stream sediments were found in the Ailaoshan metamorphic belt. Gold deposits were found to be associated with ultramafic intrusives within the Ailaoshan metamorphic belt and the ultramafic instrusives are associated with principal component images that represent multi-element associations related to gold mineralization. The first two principal components possibly represent two different types of gold associations and phases of mineralization. The study demonstrates the usefulness of applying PCA to geochemical data to produce maps that reveal different associations useful for gold exploration.
Investigation into the impact of abstraction on epiphyte species at Denge in Dungeness Special Area of Conservation
Authors: Rigg J.C. , Sage R.C.
Published: October 2006

Dungeness in Kent is the largest shingle system in the British Isles, and comprises five distinct beaches. Denge Beach is the largest of these beaches and contains a series of open water bodies, which support a diversity of fauna and flora. Gravel extraction and water abstraction for public supply has been present in the Denge area since the end of the 19th century. A deterioration of a number of patches of blackthorn (
Prunus spinosa
) scrub and important epiphyte species found on the blackthorns was observed during the early 1990s. This paper examines the nature of the shingle aquifer, water-level fluctuations, the influence of human activity, and their relationship with the deterioration of blackthorn and epiphyte communities. It is found that water levels have steadily risen since the early 1990s and the deterioration of blackthorn scrub was probably related to high chloride levels caused by ingress of seawater.
Immunotoxin Treatment of Cancer
Authors: Pastan Ira , Hassan Raffit , FitzGerald David J. , Kreitman Robert J.
Published: October 2006

Immunotoxins are proteins used to treat cancer that are composed of an antibody fragment linked to a toxin. The immunotoxin binds to a surface antigen on a cancer cell, enters the cell by endocytosis, and kills it. The most potent immunotoxins are made from bacterial and plant toxins. Refinements over many years have produced recombinant immunotoxins; these therapeutic proteins are made using protein engineering. Individual immunotoxins are designed to treat specific cancers. To date, most success has been achieved treating hematologic tumors. Obstacles to successful treatment of solid tumors include poor penetration into tumor masses and the immune response to the toxin component of the immunotoxin, which limits the number of cycles that can be given. Strategies to overcome these limitations are being pursued.
Modeling Self-Assembly and Phase Behavior in Complex Mixtures
Authors: Balazs Anna C.
Published: October 2006

Using a variety of computational techniques, I investigate how the self-assembly of complex mixtures can be guided by surfaces or external stimuli to form spatially regular or temporally periodic patterns. Focusing on mixtures in confined geometries, I examine how thermodynamic and hydrodynamic effects can be exploited to create regular arrays of nanowires or monodisperse, particle-filled droplets. I also show that an applied light source and chemical reaction can be harnessed to create hierarchically ordered patterns in ternary, phase-separating mixtures. Finally, I consider the combined effects of confining walls and a chemical reaction to demonstrate that a swollen polymer gel can be driven to form dynamically periodic structures. In addition to illustrating the effectiveness of external factors in directing the self-organization of multicomponent mixtures, the selected examples illustrate how coarse-grained models can be used to capture both the equilibrium phase behavior and the dynamics of these complex systems.
Theoretical Studies of Photoinduced Electron Transfer in Dye-Sensitized TiO2
Authors: Duncan Walter R. , Prezhdo Oleg V.
Published: October 2006

This review describes recent research into the properties of the chromophore-TiO2 interface that forms the basis for photoinduced charge separation in dye-sensitized semiconductor solar cells. It focuses particularly on an atomistic picture of the electron-injection dynamics. The interface offers an excellent case study, pertinent as well to a variety of other photovoltaic systems, photo- and electrochemistry, molecular electronics, analytical detection, photography, and quantum confinement devices. The differences between chemists’ and physicists’ models for describing molecules and bulk materials, respectively, create challenges for the characterization of interfaces that include both of these components. We give an overall picture of the interface by starting with a description of the properties of the chromophores and semiconductor separately, and then by discussing the coupled system, including the chromophore-semiconductor binding, electronic structure, and electron-injection dynamics. Explicit time-dependent modeling is particularly valuable for an understanding of the ultrafast electron injection because it shows a variety of individual injection events with well-defined dynamical features that cannot be made apparent by an average reaction-rate description.
Pharmacokinetics and Toxicity of Weekly Docetaxel in Older Patients
Authors: Hurria Arti , Fleming Mark T. , Baker Sharyn D. , Kelly Wm. Kevin , Cutchall Katie , Panageas Katherine , Caravelli James , Yeung Henry , Kris Mark G. , Gomez Jorge , Miller Vincent A. , D'Andrea Gabriella , Scher Howard I. , Norton Larry , Hudis Clifford
Published: October 2006

Purpose: To evaluate the pharmacokinetics of weekly docetaxel in a cohort of older patients with metastatic cancer and to explore the relationship of pharmacokinetic variables, Erythromycin Breath Test results, age, geriatric assessment variables, and toxicity to therapy.

Experimental Design: Twenty patients ages ≥65 years with metastatic breast, prostate, or lung cancer entered an Institutional Review Board–approved protocol to evaluate the pharmacokinetics of weekly docetaxel administered at 35 mg/m2 i.v. for 3 weeks followed by a 1-week break. The Erythromycin Breath Test and geriatric assessment were done before the first dose. Blood samples were collected for pharmacokinetic analysis with the first dose of docetaxel.

Results: Of the 20 patients who entered the study, 19 were evaluable. There were no age-related differences in the pharmacokinetics of weekly docetaxel. Fifty-eight percent (11 of 19) experienced grade ≥3 toxicity: 16% (3 of 19) grade ≥3 hematologic toxicity, and 53% (10 of 19) grade ≥3 nonhematologic toxicity. There was an association between the Erythromycin Breath Test results and docetaxel pharmacokinetic variables; however, there was no association between Erythromycin Breath Test results or docetaxel pharmacokinetics with frequency of grade ≥3 toxicity.

Conclusions: Despite no statistically significant age-related differences in weekly docetaxel pharmacokinetics, over half of these older patients experienced a grade ≥3 toxicity at the 35 mg/m2 starting dose. We advocate a starting dose of 26 mg/m2 on this weekly schedule and dose escalating if no toxicity.
Prognostic Value of Prostate Secretory Protein of 94 Amino Acids and its Binding Protein after Radical Prostatectomy
Authors: Reeves Jonathan R. , Dulude Hélène , Panchal Chandra , Daigneault Luc , Ramnani Dharam M.
Published: October 2006

Purpose: To establish the prognostic value of total and free prostate secretory protein of 94 amino acids (PSP94) and the PSP94-binding protein (PSPBP) following radical prostatectomy.

Experimental Design: One hundred and eighty-five serum samples were obtained from patients with localized prostate cancer prior to treatment with radical prostatectomy at Virginia Urology (Richmond, VA). Patients were followed up for a median of 48 months (range, 1-66 months) and biochemical relapse was indicated as total prostate-specific antigen (tPSA) levels increasing to >0.1 ng/mL. The available clinical variables included initial tPSA, Gleason score, surgical margin status, and clinical stage. Total PSP94, free PSP94, and the PSPBP were quantified in the pretreatment serum using new ELISA tests (Medicorp, Inc. and Ambrilia Biopharma, Inc., Montreal, Quebec, Canada). Univariate and multivariate Cox proportional hazards models were used to assess the ability of PSP94 and PSPBP to predict time to recurrence.

Results: Thirty-one patients had biochemical recurrence. Gleason score, margin status, clinical stage, and initial tPSA significantly predicted recurrence risk (all P < 0.001). In addition, PSPBP was negatively associated with recurrence risk (P = 0.005), and, consistent with previous studies, the bound/free PSP94 ratio was positively associated with recurrence risk (P = 0.008). Multivariate analysis showed that PSPBP, as well as the bound/free PSP94 ratio, were independent predictors of biochemical relapse risk adjusting for tPSA, Gleason score, and margin status.

Conclusions: Bound/free PSP94 and PSPBP are novel and independent prognostic markers following radical prostatectomy for prostate cancer.
A Homeobox Protein, Prox1, Is Involved in the Differentiation, Proliferation, and Prognosis in Hepatocellular Carcinoma
Authors: Shimoda Masayuki , Takahashi Meiko , Yoshimoto Takanobu , Kono Tomoya , Ikai Iwao , Kubo Hajime
Published: October 2006

Purpose: It has been shown that a lymphatic differentiation master gene, prox1, also plays an essential role in fetal hepatocyte migration. Its expression is detected in embryonic hepatoblasts and in adult hepatocytes. Hepatoma cells are similar to embryonic hepatoblasts to a certain extent because they both proliferate and invade the surrounding tissue. To address the possibility that Prox1 may be involved in the tumorigenesis of hepatocellular carcinoma (HCC), human clinical samples were analyzed.

Experimental Design: To screen prox1 as a potential tumor suppressor gene, its expression was analyzed in HCC cell lines and in human HCC tissues. Its growth-conferring abilities were assessed by transiently overexpressing Prox1 in HCC cell lines and by knocking down its expression by RNA interference.

Results: We found that there was a significant correlation between Prox1 expression and the differentiation scores of the tumors. Subsequently, we also showed that low expression of Prox1 in tumors was closely associated with a poor prognosis. The specific knockdown of Prox1 by RNA interference strongly accelerated in vitro cell growth, whereas the overexpression of Prox1 greatly suppressed the growth.

Conclusions: Our results suggest that Prox1 is involved in the differentiation and progression of HCC, and thus it may be a candidate for the development of novel diagnostic and therapeutic strategies for HCC.
GROα Is Highly Expressed in Adenocarcinoma of the Colon and Down-Regulates Fibulin-1
Authors: Wen Yu , Giardina Sarah F. , Hamming David , Greenman Jennifer , Zachariah Emmanuel , Bacolod Manny D. , Liu Hao , Shia Jinru , Amenta Peter S. , Barany Francis , Paty Phillip , Gerald William , Notterman Daniel
Published: October 2006

Purpose: The growth-related oncogene α (GROα) is a secreted interleukin-like molecule that interacts with the CXCR2 G-protein–coupled receptor. We found that the mRNA and protein products of GROα are more highly expressed in neoplastic than normal colon epithelium, and we studied potential mechanisms by which GROα may contribute to tumor initiation or growth.

Experimental Design: Cell lines that constitutively overexpress GROα were tested for growth rate, focus formation, and tumor formation in a xenograft model. GROα expression was determined by Affymetrix GeneChip (241 microdissected colon samples), real-time PCR (n = 32), and immunohistochemistry. Primary colon cancer samples were also employed to determine copy number changes and loss of heterozygosity related to the GROα and fibulin-1 genes.

Results: In cell cultures, GROα transfection transformed NIH 3T3 cells, whereas inhibition of GROα by inhibitory RNA was associated with apoptosis, decreased growth rate, and marked up-regulation of the matrix protein fibulin-1. Forced expression of GROα was associated with decreased expression of fibulin-1. Expression of GROα mRNA was higher in primary adenocarcinomas (n = 132), adenomas (n = 32), and metastases (n = 52) than in normal colon epithelium (P < 0.001). These results were confirmed by real-time PCR and by immunohistochemistry. Samples of primary and metastatic colon cancer showed underexpression of fibulin-1 when compared with normal samples. There were no consistent changes in gene copy number of GROα or fibulin-1, implying a transcriptional basis for these findings.

Conclusion: Elevated expression of GROα is frequent in adenocarcinoma of the colon and is associated with down-regulation of the matrix protein fibulin-1 in experimental models and in clinical samples. GROα overexpression abrogates contact inhibition in cell culture models, whereas inhibition of GROα expression is associated with apoptosis. Importantly, coexpression of fibulin-1 with GROα abrogates key aspects of the transformed phenotype, including tumor formation in a murine xenograft model. Targeting GRO proteins may provide new opportunities for treatment of colon cancer.
Gene Therapy Using Adenovirus-Mediated Full-length Anti-HER-2 Antibody for HER-2 Overexpression Cancers
Authors: Jiang Minghong , Shi Wenfang , Zhang Qi , Wang Xinhua , Guo Minggao , Cui Zhenfu , Su Changqin , Yang Qing , Li Yuemin , Sham Jonathan , Liu Xinyuan , Wu Mengchao , Qian Qijun
Published: October 2006

Purpose: Therapeutic monoclonal antibody is increasingly applied in many clinical applications, although complicated technologies and high cost still limit their wide applications. To obtain the sustained serum antibody concentration with one single injection and lower the cost of antibody protein therapy, an adenovirus-mediated full-length antibody gene therapy was developed.

Experimental Design: Full-length antibody light-chain and heavy-chain sequences were linked with internal ribosome entry site and constructed into adenoviral vector under the control of cytomegalovirus promoter. Antibody expression in vitro and in vivo were tested with ELISA, and its antitumor efficacy was evaluated in SKOV-3-inoculated nude mice.

Results: Ad5-TAb–generated anti-HER-2 antibody presented the similar binding specificity with commercial trastuzumab. A single i.v. injection of 2 × 109 plaque-forming units of Ad5-TAb per mouse resulted in not only a sustained over 40 μg/mL serum antibody level for at least 4 weeks but also significant tumor elimination in the ovarian cancer SKOV-3-inoculated nude mice.

Conclusions: An in vivo full-length antibody gene delivery system allows continuous production of a full-length antibody at high concentration after a single administration. Bioactive antibody macromolecules can be generated via gene transfer in vivo. All the data suggest that this novel adenovirus-mediated antibody gene delivery can be used for the exploitation of antibodies, without being hampered by the sophisticated antibody manufacture techniques and high cost, and, furthermore, can shorten the duration and reduce the expense of antibody developments.
Breast Cancer: Bisphosphonate Therapy for Metastatic Bone Disease
Authors: Body Jean-Jacques
Published: October 2006

The indications of bisphosphonate therapy in breast cancer patients go from the correction of hypercalcemia to the prevention of cancer treatment-induced bone loss. Bisphosphonates are part of our therapeutic armamentarium against metastatic bone pain, and at least 50% of the patients benefit from a clinically relevant analgesic effect. Placebo-controlled trials with oral or i.v. bisphosphonates have shown that prolonged administration can reduce the frequency of skeletal-related events by 30% to 40%. The superiority of zoledronic acid compared with pamidronate has been shown by a multiple-event analysis in a large randomized trial. The short infusion time of zoledronic acid also constitutes a convenient therapy. Where available, oral ibandronate offers an interesting alternative, especially for patients receiving hormone therapy. There are some toxicity concerns with the prolonged use of bisphosphonates. The occasional renal toxicity of zoledronic acid has led to the recommendation to monitor renal function before each infusion and to adjust the dose according to creatinine clearance. Osteonecrosis of the jaw could occur in up to 2.5% of breast cancer patients during long-term bisphosphonate therapy. It is often a significant complication that seems to be linked with the duration of therapy.
A Phase I Dose Escalation Study with Anti-CD44v6 Bivatuzumab Mertansine in Patients with Incurable Squamous Cell Carcinoma of the Head and Neck or Esophagus
Authors: Tijink Bernard M. , Buter Jan , de Bree Remco , Giaccone Giuseppe , Lang Margreet S. , Staab Alexander , Leemans C. René , van Dongen Guus A.M.S.
Published: October 2006

Purpose: To assess safety, pharmacokinetics, maximum tolerated dose, and preliminary efficacy of bivatuzumab mertansine. Bivatuzumab is a humanized monoclonal antibody directed against CD44v6, which previously seemed to be safe in phase I radioimmunotherapy trials, whereas the conjugated mertansine is a potent maytansine derivative.

Experimental Design: Patients with incurable squamous cell carcinoma of the head and neck or esophagus were eligible. Bivatuzumab was given weekly for 3 consecutive weeks by i.v. infusion. One patient was planned to be treated at each dose tier as long as toxicity did not reach grade 2; otherwise, three patients had to be treated until dose-limiting toxicity occurred. Starting dose was 20 mg/m2 and dose was subsequently escalated in steps of 20 mg/m2. Patients without disease progression and not experiencing dose-limiting toxicity were eligible for repeated courses. Blood serum samples were taken throughout the treatment period to determine the pharmacokinetic properties of bivatuzumab mertansine and to assess the human anti–bivatuzumab mertansine antibody response.

Results: Seven patients received a total of 23 weekly doses of bivatuzumab mertansine. One patient at the 100 mg/m2 and one at the 120 mg/m2 level experienced stable disease during treatment phase but also developed grade 1 skin toxicity (desquamation). One of them received a second treatment course. At the highest dose level achieved in this study (140 mg/m2), one patient developed toxic epidermal necrolysis after two infusions and died. Massive apoptosis of skin keratinocytes had occurred, whereas only symptomatic therapy for skin toxicity was available. The risk-benefit assessment of all patients treated in the total phase I program (4 clinical trials, 70 patients) turned out to be negative after consideration of this case of a toxic epidermal necrolysis and the skin-related adverse events observed in the other trials. Therefore, development of the conjugate was discontinued. Interindividual variability in pharmacokinetic variables was low and exposure to BIWI 1 increased proportionally with dose. No anti–bivatuzumab mertansine reactions were observed.

Conclusion: The main toxicity of bivatuzumab mertansine was directed against the skin, most probably due to CD44v6 expression in this tissue. The majority of skin reactions was reversible; however, one fatal drug-related adverse event had occurred. Clinical development was discontinued before reaching maximum tolerated dose.
Targeting Bone Metastasis in Prostate Cancer with Endothelin Receptor Antagonists
Authors: Carducci Michael A. , Jimeno Antonio
Published: October 2006

Recent advances in the understanding of prostate cancer biology and its progression to bone metastasis have led to the development of drugs directed against precise molecular alterations in the prostate tumor cell and host cells in the normal bone environment such as osteoclasts and osteoblasts. Endothelins (ETs) and their receptors have emerged as a potential target in prostate cancer bone metastasis. By activating the ETA receptor, ET-1 is pathogenically involved in facilitating several aspects of prostate cancer progression, including proliferation, escape from apoptosis, invasion, and new bone formation, processes that are general to many malignancies. Notwithstanding, there are a number of features specifically driven by the ET axis in prostate cancer, such as creating and perpetuating a unique interaction between the metastatic prostate cancer cell and the bone microenvironment (osteoblast, osteoclast, and stroma) or altering the equilibrium in pain modulation. These features have led to the preferential clinical evaluation of atrasentan (ABT-627) as a biological therapy in prostate carcinoma, first in hormone-refractory prostate cancer. Biological activity of atrasentan in patients with prostate cancer has been shown by the suppression of biochemical markers of prostate cancer progression in bone, and clinical activity is evidenced by a consistent trend demonstrating a delay in time to disease progression when compared with placebo, especially in patients with bone metastases. Further studies of atrasentan and other selective ET-1 antagonists (ZD4054) are ongoing.
Clinical Features of Metastatic Bone Disease and Risk of Skeletal Morbidity
Authors: Coleman Robert E.
Published: October 2006

The skeleton is the most common organ to be affected by metastatic cancer and the site of disease that produces the greatest morbidity. Skeletal morbidity includes pain that requires radiotherapy, hypercalcemia, pathologic fracture, and spinal cord or nerve root compression. From randomized trials in advanced cancer, it can be seen that one of these major skeletal events occurs on average every 3 to 6 months. Additionally, metastatic disease may remain confined to the skeleton with the decline in quality of life and eventual death almost entirely due to skeletal complications and their treatment. The prognosis of metastatic bone disease is dependent on the primary site, with breast and prostate cancers associated with a survival measured in years compared with lung cancer, where the average survival is only a matter of months. Additionally, the presence of extraosseous disease and the extent and tempo of the bone disease are powerful predictors of outcome. The latter is best estimated by measurement of bone-specific markers, and recent studies have shown a strong correlation between the rate of bone resorption and clinical outcome, both in terms of skeletal morbidity and progression of the underlying disease or death. Our improved understanding of prognostic and predictive factors may enable delivery of a more personalized treatment for the individual patient and a more cost-effective use of health care resources.