bluuebunny/crossref_metadata_2025 huggingface dataset:
Low Temperature Plasma Enhanced Chemical Vapor Deposition-Synthesized Electrochromic MoOxCy Thin Films for Flexible Electrochromic Devices
Authors: Lin Yung-Sen , Lai Jhen-Yi
Published: January 2012

An investigation is conducted into the electrochromic organomolybdenum oxide (MoO
x
C
y
) films synthesized onto 60 Ω/□ flexible poly(ethylene terephthalate) (PET)/indium tin oxide (ITO) substrates using low temperature (∼23 °C) plasma-enhanced chemical vapor deposition (PECVD). The PECVD-synthesized MoO
x
C
y
films are proven to offer remarkable electrochromic performance. Cyclic voltammetry switching measurements reveal that only low driving voltages from -1 to 1 V are needed to provide reversible Li+ ion intercalation and de-intercalation in a 1 M LiClO4-propylene carbonate (PC) electrolyte. Light modulation with transmittance variation of up to 65.2%, optical density change of 0.63 and coloration efficiency of 35 cm2/C are achieved at a wavelength of 608 nm for 150 cycles of Li+ intercalation and de-intercalation. PECVD-synthesized MoO
x
C
y
thin films show excellent electrochromic properties for applications in flexible electrochromic devices.
Growth Enhancement of Radish Sprouts Induced by Low Pressure O2Radio Frequency Discharge Plasma Irradiation
Authors: Kitazaki Satoshi , Koga Kazunori , Shiratani Masaharu , Hayashi Nobuya
Published: January 2012

We studied growth enhancement of radish sprouts (Raphanus sativusL.) induced by low pressure O2radio frequency (RF) discharge plasma irradiation. The average length of radish sprouts cultivated for 7 days after O2plasma irradiation is 30–60% greater than that without irradiation. O2plasma irradiation does not affect seed germination. The experimental results reveal that oxygen related radicals strongly enhance growth, whereas ions and photons do not.
Effects of Irradiation with Ions and Photons in Ultraviolet–Vacuum Ultraviolet Regions on Nano-Surface Properties of Polymers Exposed to Plasmas
Authors: Cho Ken , Takenaka Kosuke , Setsuhara Yuichi , Shiratani Masaharu , Sekine Makoto , Hori Masaru
Published: January 2012

The interactions of ions and photons in ultraviolet (UV) and vacuum ultraviolet (VUV) regions from argon plasmas with polymer surfaces were investigated by of depth analysis of chemical bonding states in the nano-surface layer of poly(ethylene terephthalate) (PET) films via conventional X-ray photoelectron spectroscopy (XPS) and hard X-ray photoelectron spectroscopy (HXPES). The PET films were exposed to argon plasmas by covering the PET films with MgF2 and quartz windows as optical filters to compare the irradiation effects with ions and photons. The conventional XPS results indicated that oxygen functionalities (the C–O bond and the O=C–O bond) were degraded by ion bombardment in the shallower region up to about 10 nm from the surface, whereas the effect of photoirradiation in the UV and VUV regions was insignificant. The HXPES analysis showed that irradiation with ions and photons did not cause serious damage in chemical bonding states in the deeper region up to about 50 nm from the surface.
Control of Super Hydrophobic and Super Hydrophilic Surfaces of Carbon Nanowalls Using Atmospheric Pressure Plasma Treatments
Authors: Watanabe Hitoshi , Kondo Hiroki , Sekine Makoto , Hiramatsu Mineo , Hori Masaru
Published: January 2012

Super hydrophobic and super hydrophilic surface treatment methods for carbon nanowalls (CNWs) which are carbon nanostructures consisting of stacks of graphene sheets vertically standing on substrates and having ultra high aspect ratios of over 50, were developed using atmospheric pressure plasma, and their mechanisms were discussed on the basis of the elemental compositions of surfaces. The contact angle of water droplet on CNWs markedly decreased from 137.3 to 6.2° with the atmospheric pressure plasma treatments using Ar gas. This indicates the super hydrophobic and super hydrophilic transition of CNW surfaces. Although a morphological change was hardly found, the surface compositions of fluorine and oxygen atoms markedly changed after the plasma treatment for only 5 s. Furthermore, the treatment time dependence of the surface tension of CNWs indicates two different mechanisms at earlier and later stages of surface modification using atmospheric pressure plasma.
Plasma-Enhanced Surface Modification of Sprayed Carbon Nanotube Electrodes for Lithographically Integrated Biosensing System
Authors: Jin Joon-Hyung , Kim Joon Hyub , Lee Jun-Yong , Lee Cheol Jin , Min Nam Ki
Published: January 2012

A sprayed carbon nanotube (CNT)-modified working electrode was successfully integrated into an electrochemical three-electrode system based on a glass substrate. The integrated biosensing system was fabricated through a series of photolithographic patterning and plasma etching processes. A CNT-dispersed solution was sprayed on the three-electrode system, and the CNT-modified surface was treated with O2 plasma to pattern, clean, and activate the CNT layer. The optimized plasma treatment conditions were verified in terms of plasma power and treatment time by scanning electron microscopy (SEM), cyclic voltammetry (CV), and X-ray photoelectron spectroscopy (XPS).
Plasma Nitridation of Hydrogenated Silicon Nitride Film
Authors: Lin Chiung-Wei , Yang Ming-Hsien , Lee Yeong-Shyang
Published: January 2012

In this study, chemical-vapor-deposited silicon nitride films were subjected to a novel nitridation process by use of self-biased nitrogen plasma. The film structure and electrical properties such as chemical bonding, surface morphology, dielectric strength, and the capacitance–voltage hysteresis of a metal–insulator–semiconductor device were improved. This was because the hydrogen and oxygen atoms within the silicon nitride film were replaced by the introduced energetic nitrogen atoms. With the optimized self-bias plasma, there were many new silicon–nitrogen bonds formed in the silicon film. These newly formed Si–N bonds reduced the gate leakage of the nitrified device to one order less than that of the non-nitrified device and the dielectric strength can be improved from 7.27 to 9.31 MV/cm.
Single-Step Synthesis of Al-Doped TiO2 Nanoparticles Using Non-Transferred Thermal Plasma Torch
Authors: Tsai Cheng-Yen , Hsi Hsing-Cheng , Bai Hsunling , Fan Kuo-Shuh , Sun Hung-Dar
Published: January 2012

Al-doped TiO2 nanoparticles possessing visible-light photocatalytic activity were fabricated with an atmospheric-pressure thermal plasma system via a single-step direct combination of vaporized Ti, Al, and O2. Pure Ti and Al2O3 powders and ultrahigh-purity O2 were used as the precursors. The experimental results showed that the size of synthesized TiO2 was between 10 and 105 nm. Nevertheless, the nanoparticles with sizes smaller than 50 nm accounted for approximately 80% of the total number. The observed size reduction appeared to be the suppression on particle growth due to the introduction of Al species into TiO2 crystal. The largest specific surface area of the Al-doped TiO2 was 44 m2·g-1. The anatase phase was noticeably decreased with increasing the Al2O3 addition. The absorption spectra of Al-doped TiO2 shifted from UV to visible-light region with respect to an increase in Al2O3 addition. Oxygen in the formed TiO2 was found to be in TiO2 crystal lattice and in surface hydroxyl groups. Both Ti4+ and Ti3+ existed in the formed TiO2. However, the Ti3+ amount significantly increased with increasing Al2O3 addition due to Al/Ti substitution and the resulted oxygen vacancy.
Effect of Dynamic Bias Stress in Short-Channel (L=1.5 µm) p-Type Polycrystalline Silicon Thin-Film Transistors
Authors: Choi Sung-Hwan , Mo Yeon-Gon , Kim Hye-Dong , Han Min-Koo
Published: January 2012

We have investigated the stability of short-channel (1.5 µm) p-type polycrystalline silicon (poly-Si) thin film transistors (TFTs) under AC bias stress. The threshold voltage of the short-channel (L=1.5 µm) poly-Si TFT was increased by about -7.44 V after AC bias stress, whereas the threshold voltage of the long-channel poly-Si TFT was relatively stable. A two-step degradation process was also observed. In the first step, the threshold voltage of short-channel poly-Si TFTs underwent a consistent positive shift for 100 s. In contrast, the threshold voltage started to undergo a negative shift when accompanied by significant degradation in the subthreshold region. This negative shift of threshold voltage and the significantly degraded subthreshold swing value in the short-channel TFT under dynamic stress may be mainly due to the generation of stress-induced deep- and shallow-level trapping states near the drain junction.
Universal Expression of the Optical Power Dissipation in Multilayer Structures with Complex Permittivity and Permeability
Authors: Kim Jungho , Kim Kyoung-Youm , Kim Sungchul
Published: January 2012

A general simple expression is derived for the time-average optical power dissipation Q in plasmonic or metamaterial-based multilayer structures, which have complex permittivity and/or complex permeability. We demonstrate that the derived general expression for Q, including the optical interference effect, is in the same form as one based on the Poynting's energy theorem, where the optical interference effect is not explicitly considered. The universal expression of Q, derived under the assumption of complex permittivity and permeability, reduces to other well-known simple forms, which are only valid when either permittivity or permeability is complex. The derived general expression of Q provides with a strong theoretical background to predict the optical absorption or loss in the design of plasmonic or metamaterial-based nanostructures.
Effect of AC Electrodeposition Conditions on Microstructure and Magnetic Properties of CoxNi1-xNanowire Arrays Embedded in Anodic Aluminum Oxide Template
Authors: Kashi Mohammad Almasi , Ramazani Abdolali , Akhshi Nasrin , Esmaeily Amir Sajad
Published: January 2012

CoxNi1-xalloy nanowire arrays were fabricated by ac electrodeposition technique into nanoporous alumina membranes. The effect of frequency, composition and electrolyte on the crystalline structure and magnetic properties of nanowire arrays were investigated. Different alloy nanowires were prepared with 50, 100, 200, 300, 400, 500, 800, and 1000 Hz deposition frequencies. Obtained results showed both the coercivity and squareness (parallel to the nanowires axis) weakly depend on the frequency and electrolyte. The coercivity initially decreased with increase in frequency then increased. This trend was more pronounced for Co-rich CoxNi1-xnanowires. A coercivity of 1560 Oe was obtained which may be due to the predomination of (002) direction at 1100 Hz deposition frequency.
Ion Conductivity of Ta2O5 Solid Electrolyte Thin Film Prepared by Combination Sputtering with Radio Frequency Oxygen Plasma Irradiation
Authors: Noguchi Daisuke , Taneda Hiroshi , Higashimaru Yukie , Kawano Yoshihiko , Sei Fumihiro
Published: January 2012

In light of the need to simplify combination sputtering systems and to use them to fabricate thin-film electronic materials, we fabricated a Ta2O5 solid electrolyte thin-film that exhibits superior ion conductivity by using combination sputtering with RF oxygen plasma irradiation. The formation of Ta2O5 thin films using this technique was confirmed by Rutherford backscattering spectroscopy and the effectiveness of the resulting thin film as a solid electrolyte was demonstrated by its ion conductivity, which was determined by AC impedance measurement.
Vacuum Ultraviolet and Ultraviolet Radiation-Induced Effect of Hydrogenated Silicon Nitride Etching: Surface Reaction Enhancement and Damage Generation
Authors: Fukasawa Masanaga , Miyawaki Yudai , Kondo Yusuke , Takeda Keigo , Kondo Hiroki , Ishikawa Kenji , Sekine Makoto , Matsugai Hiroyasu , Honda Takayoshi , Minami Masaki , Uesawa Fumikatsu , Hori Masaru , Tatsumi Tetsuya
Published: January 2012

Photon-enhanced etching of SiN
x
:H films caused by the interaction between vacuum ultraviolet (VUV)/ultraviolet (UV) radiation and radicals in the fluorocarbon plasma was investigated by a technique with a novel sample setup of the pallet for plasma evaluation. The simultaneous injection of UV radiation and radicals causes a dramatic etch rate enhancement of SiN
x
:H films. Only UV radiation causes the film shrinkage of SiN
x
:H films owing to hydrogen desorption from the film. Capacitance–voltage characteristics of SiN
x
:H/Si substrates were studied before and after UV radiation. The interface trap density increased monotonically upon irradiating the UV photons with a wavelength of 248 nm. The estimated effective interface trap generation probability is 4.74 ×10-7 eV-1·photon-1. Therefore, the monitoring of the VUV/UV spectra during plasma processing and the understanding of its impact on the surface reaction, film damage and electrical performance of underlying devices are indispensable to fabricate advanced devices.
Splitter Microchannel Network for Equal Plasma Flow Division on Compact Disk Microfluidic Chip
Authors: Kuo Ju-Nan , Lee Wen-Wai , Chen Jing-Ying
Published: January 2012

In this paper, we present two splitter microchannel networks (U- and Y-shaped) for accomplishing the equal division of a plasma flow on a rotating compact disk (CD) microfluidic chip. A splitter microchannel including a microchannel network consisting of a straight main microchannel and two branching microchannels has been proposed. It is shown that the Coriolis force generated as the chip rotates causes a nonequal division of the plasma flow between the two branches of the splitter network when they are assigned identical geometry parameters. Accordingly, a series of computational fluid dynamics (CFD) simulations are performed to determine the optimal geometry parameters of the upper and lower branches in the U- and Y-shaped networks. The experimental results show that the optimized splitter networks cause a variation of no more than 0.2 nL in the plasma samples collected from the upper and lower branches.
Streak Observation System for DC Pre-breakdown Using an Image Guide Scope
Authors: Mohamed Amir Izzani , Kadowaki Kazunori
Published: January 2012

A light delay path and a streak camera are combined as a dc pre-breakdown optical observation system. The light delay path in this study is a 20-m-long image guide scope (IGS). The IGS will delay the pre-breakdown light for 100 ns before reaching the streak camera. During this time, the streak camera will be triggered and a streak image of pre-breakdown light can be obtained. Previously, either an image of pre-breakdown light (weak discharge light at either one of the electrode or in the bulk of liquid sample) or an image of complete breakdown light (strong discharge light bridging across the electrodes) could be obtained by using an old system (IGS and a film camera photographic observation system). The transition process from pre-breakdown to complete breakdown light was unknown. The study is dedicated to setup and clarified the combination of the streak camera and IGS system, so that it can be used to clarify the transition process.
Age of the Ballachulish and Glencoe Igneous Complexes (Scottish Highlands), and paragenesis of zircon, monazite and baddeleyite in the Ballachulish Aureole
Authors: Fraser G.L. , Pattison D.R.M. , Heaman L.M.
Published: January 2012

U–Pb zircon ages are presented for the Ballachulish Igneous Complex (
207
Pb–
206
Pb age 427 ± 1 Ma;
206
Pb–
238
U age 423 ± 0.3 Ma) and Glencoe Volcanic Complex (
207
Pb–
206
Pb age 406 ± 6 Ma) of the Scottish Highlands. These ages are significantly more precise than pre-existing age constraints, and discriminate a previously unresolved age difference of
c
. 20 Ma between the two complexes. This difference in age provides an explanation for the
c
. 10 km difference in crustal level between the two magmatic events, and constrains exhumation rates for the Argyll region to be on average
c
. 0.4 km Ma
−1
over the period
c
. 425–405 Ma. With improved age constraints on the Ballachulish Igneous Complex in place, the associated metamorphic aureole is used as a type locality to investigate the metamorphic behaviour of the U-bearing accessory minerals baddeleyite, zircon and monazite. Baddeleyite formed in impure dolomites by the reaction of detrital zircon with dolomite and gives the same U–Pb age as the intrusive complex, consistent with its contact metamorphic origin. Detrital zircon appears to be inert throughout much of the metamorphic aureole, with contact metamorphic zircon growth being restricted to migmatite-grade rocks. A possible exception is the development of enigmatic, very narrow overgrowths at temperatures between
c
. 500 and 600 °C. Monazite exhibits a variety of textures in lower-grade parts of the aureole (<550 °C), but occurs as distinctive clusters and trails of tiny ovoid grains at temperatures above about 560–600 °C. Monazite thus appears sensitive to metamorphism at lower temperatures than zircon and may therefore be a better target for metamorphic age measurements in rocks that reach mid-amphibolite facies but do not experience partial melting.
Sea-level change and facies development across potential Triassic–Jurassic boundary horizons, SW Britain
Authors: Hesselbo Stephen P. , Robinson Stuart A. , Surlyk Finn
Published: January 2012

The Late Triassic to Early Jurassic aged succession of SW Britain (the Penarth and lower Lias Groups) comprises mudstone, sandstone and limestone strata deposited in a variety of marine to non-marine environments. Faunal and floral characteristics of these successions have led to the proposal that one location in SW England, St Audrie's Bay, should serve as the Global Stratotype Section and Point (GSSP) for the base of the Hettangian Stage and, thus, for the Triassic–Jurassic (Tr–J) boundary. The sections of SW Britain have also been used previously to infer sea-level change history and relate this to potential kill mechanisms associated with the Tr–J boundary mass extinction. Chemostratigraphic, biofacies and lithofacies data are used here to suggest alternative models of sea-level change in relation to possible Tr–J boundary horizons in the sections of SW Britain. A sea-level lowstand surface of erosion is inferred to occur within the Cotham Member of the Lilstock Formation, a unit deposited in an environment that was often subaerially exposed. In contrast to previous interpretations, the top surface of the overlying Langport Member (here inferred to be deposited on a carbonate ramp of depositional or tectonic origin) represents a drowning event of at least regional extent. All horizons regarded as plausible levels at which to place the Tr–J boundary based on fossil distributions lie within strata deposited during relative sea-level rise. However, it is doubtful whether the higher horizons proposed to mark the boundary faithfully record times of true biotic change on a global scale and, additionally, there is no positive evidence that sea-level fall had any relation to the genesis of proposed Tr–J marker horizons. It is unlikely that sea-level fall played a significant role in the Tr–J boundary extinctions in either a local or a global context.
Dating of the Ameralik dyke swarms of the Nuuk district, southern West Greenland: mafic intrusion events starting from

c

. 3510 Ma
Authors: Nutman Allen P. , Friend Clark R. L. , Bennett VICKIE C. , McGregor VIC R.
Published: January 2012

This paper presents SHRIMP U–Pb zircon dating on four Meso- to Palaeoarchaean amphibolite-facies Ameralik dykes of differing compositions scattered throughout the Palaeoarchaean (3850–3600 Ma) amphibolite–granulite-facies Itsaq Gneiss Complex in the Nuuk district, southern West Greenland. In the north of the complex near the Isua supracrustal belt, an east–west-oriented, >50 m thick metanoritic dyke, with abundant relicts of original opx + plag ± ol igneous mineralogy, gave an age of 3512 ± 7 Ma interpreted as the intrusion age (in general agreement with previous isotope dilution thermal ionization mass spectrometry data). In the same area, the best estimate for the intrusion age of a metadolerite dyke with the same orientation and similar degree of preservation is 3265 ± 15 Ma. At the mouth of Ameralik (fjord) 150 km to the SW, a large noritic Ameralik dyke, the Ugpik metadolerite, was largely recrystallized to amphibolite in the later Archaean. Relict magmatic zircon in this body implies an intrusion age of ≥3453 ± 16 Ma. In Itilleq (fjord) 60 km to the east of the Ugpik metadolerite, a dioritic component of a composite, dioritic–gabbroic intrusion cutting older, more deformed Ameralik dykes has yielded an age of 3257 ± 14 Ma for the time of intrusion. These new sensitive high-resolution ion microprobe dates on magmatic crystallization support previous field observations that the Ameralik dykes consist of several unrelated sets of dykes different in age by up to 250 Ma. The magmatic zircons in three of the dykes have 2700–2500 Ma overgrowths, interpreted to have grown during late Archaean amphibolite-facies tectonothermal events in the region. The original name ‘Ameralik dykes’ might propagate confusion that all such bodies can be regarded as the same age. Thus we recommend retaining the original definition of the Ameralik dykes but using the term ‘Ameralik dyke swarms’ to emphasize that unrelated intrusions of more than one age are present.
Early Cambrian location and affinities of the Brunovistulian terrane (Central Europe) in the light of palaeomagnetic data
Authors: Nawrocki J. , Zylińska A. , Bula Z. , Grabowski J. , Krzywiec P. , Poprawa P.
Published: January 2012

The Brunovistulian was one of the first tectonic units of Central Europe to be defined as a ‘terrane’. In spite of extensive studies, the Early Palaeozoic palaeogeographical position and provenance of this unit remains unclear. A palaeomagnetic study of the Lower Cambrian red beds and a study of the trilobite fauna were performed to provide constraints on the palaeogeographical position of the terrane in Early Cambrian time. Good quality palaeomagnetic data obtained from the Lower Cambrian red beds suggest the mixed nature of the Early Cambrian geomagnetic field and a nearly equatorial position (a palaeolatitude of
c
. 7°) of the Brunovistulian terrane in the Early Cambrian. Comparison of this palaeolatitude with existing palaeogeographical models leads to the conclusion that at this time the Brunovistulian terrane was separated by a great distance from the Avalonian margin of Gondwana. The terrane was located within the Cadomian belt, occupying a position north of the present-day northern margin of Africa. It was coupled to the present-day southern margin of Baltica during the Cambrian, when Baltica moved along the Cadomian margin of Gondwana. Another possibility is that the Brunovistulian terrane could have remained near this margin of Baltica since Grenvillian time and was incorporated into the Cadomian orogen.
Evidence of plant–insect interactions in the Upper Triassic Molteno Formation of South Africa
Authors: Scott Andrew C. , Anderson John M. , Anderson Heidi M.
Published: January 2012

The Molteno Formation of Late Triassic (Carnian) age in South Africa has yielded more than 200 plant species from 100 plant assemblages at 69 localities (30 000 catalogued slabs) as well as more than 300 species of insect. Damage to leaves caused by insects is widespread on many plant species at numerous localities. The damage includes feeding traces, predominantly continuous marginal feeding traces, leaf mines including linear and possible blotch varieties and probable leaf galls. Damaged taxa include a wide variety of gymnosperms including the conifer
Heidiphyllum
, the ginkgoaleans
Ginkgo
and
Sphenobaiera
, the peltasperms
Dicroidium
and
Dejerseya
, the pentoxyalean
Taeniopteris
and the gnetopsid
Yabeiella
. Quantitative data (>3000 specimens examined) on the insect damage were obtained for four sites: Aasvöelberg, Birds River, Kapokkraal and Waldeck. Quantitative data indicate that leaf damage between sites varies from 3 to 25% and within species from 1 to 50%. The variation in damage to the same taxon between sites, and even in the overall folivory seen at the four sites, makes the interpretation of the general levels of herbivory in the Molteno difficult to assess. Herbivory levels in Northern Hemisphere Triassic plant assemblages appear to be significantly lower than those in the Molteno, and succeeding Jurassic floras worldwide also show a low level of plant–insect interactions. It is not yet clear to what extent taphonomic bias may influence the calculation of overall herbivory levels for a given time period.
Palaeozoic accretionary and convergent tectonics of the southern Altaids: implications for the growth of Central Asia
Authors: XIAO W. , WINDLEY B.F. , BADARCH G. , SUN S. , LI J. , QIN K. , WANG Z.
Published: January 2012

The southern Altaids present a unidirectional section from Mongolia to China through an accretionary orogen that youngs progressively from Neoproterozoic in the north to Permian in the south. The orogen formed by forearc accretion of island arcs, accretionary wedges, ophiolites and Precambrian microcontinents. This regularity was upset by early growth within the ocean of arcs that later collided at the accreting continental margin, by imbrication of old ophiolites with young arcs, and by Himalayan-style thrust–nappe tectonics when an arc collided into a microcontinent. Lateral growth of the Southern Altaids represents a massive addition of juvenile material to the Palaeozoic crust.
Bile acids via FXR initiate the expression of major transporters involved in the enterohepatic circulation of bile acids in newborn mice
Authors: Cui Julia Yue , Aleksunes Lauren M. , Tanaka Yuji , Fu Zidong Donna , Guo Ying , Guo Grace Liejun , Lu Hong , Zhong Xiao-bo , Klaassen Curtis D.
Published: January 2012

The enterohepatic circulation (EHC) of bile acids (BAs) plays a pivotal role in facilitating lipid absorption. Therefore, initiation of the EHC in newborns is of crucial importance for lipid absorption from milk. The purpose of this study was to determine at what age BA transporters in liver are expressed, and the mechanism for their initiation. Serum and liver samples were collected from C57BL/6 mice at 2 days before birth and various postnatal ages. Messenger RNA assays revealed a dramatic increase at birth in the expression of the BA transporters (Ntcp, Bsep, Mrp4, Ostβ), as well as the phospholipid floppase Mdr2 in mouse liver, with the highest expression at 1 day of age. The mRNA expression of the ileal BA transporters (Ostα and Ostβ) also markedly increased at birth. Meanwhile, taurine-conjugated cholic acid markedly increased in both serum and liver of newborns, correlated with upregulation of the classic pathway of BA biosynthesis in newborn liver. The mRNA levels of the major BA sensors, FXR and PXR, were increased at 1 day of age, and their prototypical target genes were upregulated in liver. The mRNA expression of transporters involved in the EHC of BAs was similar in wild-type and PXR-null mice. In contrast, in FXR-null mice, the “ day 1 surge” pattern of Ntcp, Bsep, Ostβ, and Mdr2 was blocked in newborn mouse liver, and the induction of Ostα and Ostβ was also abolished in ileums of FXR-null mice. In conclusion, at birth, BAs from the classic pathway of synthesis trigger the induction of transporters involved in EHC of BAs in mice, through activation of the nuclear receptor FXR.
Cardio-ventilatory coupling in young healthy resting subjects
Authors: Friedman Lee , Dick Thomas E. , Jacono Frank J. , Loparo Kenneth A. , Yeganeh Amir , Fishman Mikkel , Wilson Christopher G. , Strohl Kingman P.
Published: January 2012

In this work, cardio-ventilatory coupling (CVC) refers to the statistical relationship between the onset of either inspiration (I) or expiration (E) and the timing of heartbeats (R-waves) before and after these respiratory events. CVC was assessed in healthy, young (<45 yr), resting, supine subjects ( n = 19). Four intervals were analyzed: time from I-onset to both the prior R-wave (R-to-I) and the following R-wave (I-to-R), as well as time from E-onset to both the prior R-wave (R-to-E) and following R-wave (E-to-R). The degree of coupling was quantified in terms of transformed relative Shannon entropy (tRSE), and χ2 tests based on histograms of interval times from 200 breaths. Subjects were studied twice, from 5 to 27 days apart, and the test-retest reliability of CVC measures was computed. Several factors pointed to the relative importance of the R-to-I interval compared with other intervals. Coupling was significantly stronger for the R-to-I interval, coupling reliability was largest for the R-to-I interval, and only tRSE for the R-to-I interval was correlated with height, weight, and body surface area. The high test-retest reliability for CVC in the R-to-I interval provides support for the hypothesis that CVC strength is a subject trait. Across subjects, a peak ∼138 ms prior to I-onset was characteristic of CVC in the R-to-I interval, although individual subjects also had earlier peaks (longer R-to-I intervals). CVC for the R-to-I interval was unrelated to two separate measures of respiratory sinus arrhythmia (RSA), suggesting that these two forms of coupling (CVC and RSA) are independent.
Integrative Survival-Based Molecular Profiling of Human Pancreatic Cancer
Authors: Donahue Timothy R. , Tran Linh M. , Hill Reginald , Li Yunfeng , Kovochich Anne , Calvopina Joseph H. , Patel Sanjeet G. , Wu Nanping , Hindoyan Antreas , Farrell James J. , Li Xinmin , Dawson David W. , Wu Hong
Published: January 2012

Purpose: To carry out an integrative profile of human pancreatic ductal adenocarcinoma (PDAC) to identify prognosis-significant genes and their related pathways.

Experimental Design: A concordant survival-based whole genome in silico array analysis of DNA copy number, and mRNA and miRNA expression in 25 early-stage PDAC was carried out. A novel composite score simultaneously integrated gene expression with regulatory mechanisms to identify the signature genes with the most levels of prognosis-significant evidence. The predominant signaling pathways were determined via a pathway-based approach. Independent patient cohorts (n = 148 and 42) were then used as in vitro validation of the array findings.

Results: The composite score identified 171 genes in which expressions were able to define two prognosis subgroups (P = 3.8e-5). Eighty-eight percent (151 of 171) of the genes were regulated by prognosis-significant miRNAs. The phosphoinositide 3-kinase/AKT pathway and SRC signaling were densely populated by prognosis-significant genes and driven by genomic amplification of SRC and miRNA regulation of p85α and CBL. On tissue microarray validation (n = 148), p85α protein expression was associated with improved survival for all patients (P = 0.02), and activated P-SRC (Y418) was associated shorter survival for patients with low-grade histology tumors (P = 0.04). Interacting P-SRC and p85α revealed that they define two distinct PDAC patient subgroups (P = 0.0066). Furthering the importance of these pathways, CBL protein expression was associated with improved survival (P = 0.03) on a separate cohort (n = 42).

Conclusions: These pathways and related genes may represent putative clinical biomarkers and possible targets of individualized therapy in the distinct patient subgroups they define. Clin Cancer Res; 18(5); 1352–63. ©2012 AACR.
Sunitinib Therapy for Melanoma Patients with KIT Mutations
Authors: Minor David R. , Kashani-Sabet Mohammed , Garrido Maria , O'Day Steven J. , Hamid Omid , Bastian Boris C.
Published: January 2012

Purpose: Recent studies have shown activating KIT mutations in melanoma originating from mucosa, acral, or cumulative sun-damaged skin sites. We aimed to assess the predictive role of KIT mutation, amplification, or overexpression for response to treatment with the kinase inhibitor sunitinib.

Experimental Design: Tumor tissues from 90 patients with stage III or IV acral, mucosal, or cumulative sun-damaged skin melanoma underwent sequencing of KIT, BRAF, NRAS, and GNAQ genes, FISH analysis for KIT amplification, and immunohistochemistry of KIT protein (CD117). Patients with mutations, amplifications, or overexpression of KIT were treated with sunitinib and responses measured by Response Evaluation Criteria in Solid Tumors (RECIST).

Results: Eleven percent of the melanomas tested had mutations in KIT, 23% in BRAF, 14% in NRAS, and none in GNAQ. Of 12 patients treated with sunitinib, 10 were evaluable. Of the 4 evaluable patients with KIT mutations, 1 had a complete remission for 15 months and 2 had partial responses (1- and 7-month duration). In contrast, only 1 of the 6 patients with only KIT amplification or overexpression alone had a partial response. In 1 responder with rectal melanoma who later progressed, the recurring tumor had a previously undetected mutation in NRAS, which was found in addition to the persisting mutation in KIT. Interestingly, among patients with manifest stage IV disease, KIT mutations were associated with a significantly shortened survival time (P < 0.0001).

Conclusions: Sunitinib may have activity in patients with melanoma and KIT mutations; more study is needed. KIT mutations may represent an adverse prognostic factor in metastatic melanoma. Clin Cancer Res; 18(5); 1457–63. ©2012 AACR.
CD26 Overexpression Is Associated with Prolonged Survival and Enhanced Chemosensitivity in Malignant Pleural Mesothelioma
Authors: Aoe Keisuke , Amatya Vishwa Jeet , Fujimoto Nobukazu , Ohnuma Kei , Hosono Osamu , Hiraki Akio , Fujii Masanori , Yamada Taketo , Dang Nam H. , Takeshima Yukio , Inai Kouki , Kishimoto Takumi , Morimoto Chikao
Published: January 2012

Purpose: Malignant pleural mesothelioma (MPM) is an aggressive and therapy-resistant neoplasm arising from the pleural mesothelial cells, without established indicators to predict responsiveness to chemotherapy.

Experimental Design: Our study involving 79 MPM patients showed that 73.4% of MPM expressed CD26 on cell membrane.

Results: The majority of epithelioid and biphasic types of MPM expressed CD26 on the cell membrane, whereas the sarcomatoid type showed a lack of CD26 surface expression. Although the sarcomatoid type was associated with poor prognosis (P < 0.0001), no significant relationship between CD26 expression and survival was observed. On the contrary, there was a trend for an association between response rate to chemotherapy and CD26 expression (P = 0.053), with a higher level of CD26 expression more likely to be linked to better response to chemotherapy. Moreover, CD26 expression was a significant factor associated with improved survival in patients who received chemotherapy [median survival time (MST), 18.6 vs. 10.7 months, P = 0.0083]. Furthermore, CD26 expression was significantly associated with better prognosis in patients receiving non–pemetrexed-containing regimens (MST, 14.2 vs. 7.4 months, P = 0.0042), whereas there was no significant association between CD26 expression and survival time for patients receiving pemetrexed-containing regimens. Our in vitro and microarray studies showed that mesothelioma cells expressing high CD26 displayed high proliferative activity, and CD26 expression was closely linked to cell-cycle regulation, apoptosis, and chemotherapy resistance.

Conclusions: Our results strongly suggest that CD26 is a clinically significant biomarker for predicting response to chemotherapy for MPM. Clin Cancer Res; 18(5); 1447–56. ©2012 AACR.
A Functional, New Short Isoform of Death Receptor 4 in Ewing's Sarcoma Cell Lines May be Involved in TRAIL Sensitivity/Resistance Mechanisms
Authors: Picarda Gaëlle , Surget Sylvanie , Guiho Romain , Téletchéa Stéphane , Berreur Martine , Tirode Franck , Pellat-Deceunynck Catherine , Heymann Dominique , Trichet Valérie , Rédini Françoise
Published: January 2012

Ewing's sarcoma (ES) is a high-grade neoplasm arising in bones of children and adolescents. Survival rate decreases from greater than 50% to only 20% after 5 years for patients not responding to treatment or presenting metastases at diagnosis. TRAIL, which has strong antitumoral activity, is a promising therapeutic candidate. To address TRAIL sensitivity, 7 human ES cell lines were used. Cell viability experiments [3′[1-(phenylaminocarbonyl)-3,4-tetrazolium]-bis(4-methoxy-6-nitro-)benzene sulfonic acid hydrate (XTT) assay] showed that 4 of the 7 ES cell lines were resistant to TRAIL. Western blotting and flow cytometry analyses revealed that DR5 was uniformly expressed by all ES cell lines, whereas DR4 levels were higher in sensitive cell lines. In TRAIL-sensitive TC-71 cells, knockdown of TNFRSF10A/DR4 by short hairpin RNA (shRNA) was associated with a loss of sensitivity to TRAIL, in spite of DR5 presence. Interestingly, we identified a new transcript variant that results from an alternative splicing and encodes a 310–amino acid protein which corresponds to the 468 aa of DR4 original isoform but truncated of aa 11 to 168 within the extracellular TRAIL-binding domain. According to modeling studies, the contact of this new DR4 isoform (bDR4) with TRAIL seemed largely preserved. The overexpression of bDR4 in a TRAIL-resistant cell line restored TRAIL sensitivity. TRAIL resensitization was also observed after c-FLIP knockdown by shRNA in two TRAIL-resistant cell lines, as shown by XTT assay and caspase-3 assay. The results presented in this study showed that DR4, both as the complete form or as its new short isoform, is involved in TRAIL sensitivity in ES. Mol Cancer Res; 10(3); 336–46. ©2012 AACR.
The Evolution of Drug Resistance Interpretation Algorithms: ANRS, REGA and Extension of Resistance Analysis to HIV-1 Group O and HIV-2
Authors: Eberle Josef , Gürtler Lutz
Published: January 2012

Antiretroviral drug resistance is mostly linked to a complex interaction of several amino acids with variable importance or a single amino acid. To facilitate the interpretation of observed mutation patterns, hospital university centers have developed several interpretation systems. All the currently available interpretation algorithms evolved, are being continuously updated and have been improved during the last decade. Some discrepancies are still evident that are partially smoothened by link of the individual programs with other systems. After the interpretation of HIV-1 group M subtype B mutations, a refined algorithm for the other group M subtypes was developed followed by the interpretation of HIV-1 group O and HIV-2 mutations. The process of improvement is ongoing, due to the better understanding and interpretation of single and cluster mutations and the availability of new antiretroviral substances. The knowledge gained from the experience of HIV drug resistance testing has been used to establish the interpretation of HBV polymerase mutations and will be extended for the treatment of HCV infected with protease inhibitors.
Expression of MUC1, MUC2, MUC5AC and MUC5B in Mucinous Lesions of the Breast
Authors: Kim Dokyung , Jung Woo-Hee , Koo Ja Seung
Published: January 2012

Objective: The purpose of this study was to investigate the expression of MUC1, MUC2, MUC5AC and MUC5B in breast mucinous lesions. Methods: Immunohistochemical staining of MUC1, MUC2, MUC5AC, MUC5B and synaptophysin was performed in 78 cases of mucinous carcinoma (MC), 36 cases of mucocele-like lesions (MLL) and 13 cases of solid papillary carcinoma (SPC). MC was classified as type A or type B and MLL was classified as MLL, MLL with atypical ductal hyperplasia and MLL with ductal carcinoma in situ. Results: MUC1 was expressed in MC type A and MLL with luminal/apical pattern, while MC type B and SPC showed membrano-cytoplasmic expression of MUC1 (p < 0.001). A luminal/apical or luminal/apical + cytoplasmic pattern of MUC2 expression was observed in MC type A, while MC type B and SPC showed membrano-cytoplasmic MUC2 expression (p < 0.001). On MUC5B staining, MC type A and MLL were negative, while MC type B and SPC showed membrano-cytoplasmic expression (p = 0.011). The positive rate for synaptophysin was higher in MC type B and SPC than in MLL and MC type A (p = 0.001). Conclusions: Similar MUC phenotypes were observed between MLL and MC type A and between MC type B and SPC.
The Challenges of Providing Renal Replacement Therapy in Decompensated Liver Cirrhosis
Authors: Gonwa Thomas A. , Wadei Hani M.
Published: January 2012

Development of renal failure requiring renal replacement therapy (RRT) in the cirrhotic patient is a devastating complication. Survival without RRT is less than 10% on average at 6 months. However, it is now appreciated that all renal failure in this group of patients is not due solely to hepatorenal syndrome, and the cause of the renal failure affects the prognosis. This paper reviews the prognosis depending on cause and points out the difficulty in making the correct diagnosis. Provision of RRT is difficult in this group of patients due to hypotension and coagulopathy which is highly prevalent. Survival with RRT is still poor with only 30–60% of patients surviving to liver transplant. Provision of RRT should be offered as a bridge to patients awaiting liver transplant or those undergoing liver transplant evaluation. Provision of long-term RRT is usually not indicated in other cirrhotic patients who develop a need for RRT except as a trial to see if renal function will return. The decision between intermittent hemodialysis or continuous renal replacement therapy (CRRT) is usually based on the clinical characteristics of the patient. Neither has been demonstrated to be superior to the other, although CRRT may be better tolerated in the unstable patient. CRRT is clearly indicated in cases of fulminant hepatic failure as it does not raise intracranial pressure. Provision of intraoperative CRRT during liver transplant may be indicated to help control volume and electrolytes in those patients presenting for liver transplant with renal failure. Newer extracorporeal support systems, such as extracorporeal albumin dialysis (MARS) and fractional plasma separation and adsorption with hemodialysis (Prometheus), have recently been developed to provide both renal and liver support in this group of patients. These are still considered experimental, although the MARS system has been utilized to treat patients with hepatorenal syndrome, and is available outside the United States.
Sudden Cardiac Death in Hemodialysis Patients: A Comprehensive Care Approach to Reduce Risk
Authors: Pun Patrick H. , Middleton John P.
Published: January 2012

Sudden cardiac death is a major problem in hemodialysis patients, and our understanding of this disease is underdeveloped. The lack of a precise definition tailored for use in the hemodialysis population limits the reliability of epidemiologic reports. Efforts should be directed toward an accurate classification of all deaths that occur in this vulnerable population. The traditional paradigm of disease pathophysiology based on known cardiac risk factors appears to be inadequate to explain the magnitude of sudden cardiac death risk in chronic kidney disease, and numerous unique cofactors and exposures appear to determine risk in this population. Well-designed cohort studies will be needed for a basic understanding of disease pathophysiology and risk factors, and randomized intervention trials will be needed before best management practices can be implemented. This review examines available data to describe the characteristics of the high-risk patient and suggests a comprehensive common sense approach to prevention using existing cardiovascular medications and reducing and monitoring potential dialysis-related arrhythmic triggers. Other unproven cardiovascular therapies such as implantable cardioverter defibrillators should be used on a case-by-case basis, with recognition of the associated hazards that these devices carry among hemodialysis patients.
Effects of Citrate Acid Concentrate (Citrasate®) on Heparin N Requirements and Hemodialysis Adequacy: A Multicenter, Prospective Noninferiority Trial
Authors: Sands Jeffrey J. , Kotanko Peter , Segal Jonathan H. , Ho Chiang-Hong , Usvat Len , Young Amy , Carter Mary , Sergeyeva Olga , Korth Lisa , Maunsell Eileen , Zhu Yueping , Krishnan Mahesh , Diaz-Buxo Jose A.
Published: January 2012

Background: Citrasate®, citric acid dialysate (CD), contains 2.4 mEq of citric acid (citrate), instead of acetic acid (acetate) as in standard bicarbonate dialysate. Previous studies suggest CD may improve dialysis adequacy and decrease heparin requirements, presumably due to nonsystemic anticoagulant effects in the dialyzer. Methods: We prospectively evaluated 277 hemodialysis patients in eight outpatient facilities to determine if CD with reduced heparin N (HN) would maintain dialyzer clearance. Subjects progressed through four study periods [baseline (B): bicarbonate dialysate + 100% HN; period 1 (P1): CD + 100% HN; period 2 (P2): CD + 80% HN; period 3 (P3): CD + 66.7% HN]. The predefined primary endpoint was noninferiority (margin –8%) of the percent change in mean dialyzer conductivity clearance between baseline and P2. Results: Subjects were 57.4% male, 41.7% white, 54.3% black, and 44.4% diabetic; mean age was 59 ± 14.4 years; mean time on dialysis was 1,498 ± 1,165 days; 65.7% had arteriovenous fistula, 19.9% arteriovenous graft, 14.4% catheters, and 27.8% used antiplatelet agents. Mean dialyzer clearance increased 0.9% (P1), 1.0% (P2), and 0.9% (P3) with CD despite heparin reduction. SpKt/V remained stable (B: 1.54 ± 0.29; P1: 1.54 ± 0.28; P2: 1.55 ± 0.27; P3: 1.54 ± 0.26). There was no significant difference in dialyzer/dialysis line thrombosis, post-HD time to hemostasis, percent of subjects with adverse events (AEs), or study-related AEs. Conclusions: CD was safe, effective, and met all study endpoints. Dialyzer clearance increased approximately 1% with CD despite 20–33% heparin reduction. Over 92% of P3 subjects demonstrated noninferiority of dialyzer clearance with CD and 33% HN reduction. There was no significant difference in dialyzer clotting, bleeding, or adverse events.
Long-Term Management of the Kidney Transplant Recipient
Authors: Schaefer Heidi M.
Published: January 2012

Due to the successes of kidney transplantation, patients with allografts are enjoying long-term survival. In addition to care of the allograft with lifelong administration of immunosuppressive medications, common medical conditions must be recognized and managed appropriately. With constraints on the transplant centers and patient considerations of finance and geography, it is recognized that community providers will play an ever increasing role in the care of the kidney transplant recipient. Guidelines for understanding and managing some of the more important common general medical problems, including care as it relates to cardiovascular disease, chronic kidney disease, transplant-related issues, and general health maintenance, are reviewed in this article.
Peritoneal Dialysis Is Not a Superior Therapy to Hemodialysis: A Comparison
Authors: Stokes John B.
Published: January 2012

After initial reports suggesting that patients initiating peritoneal dialysis (PD) had better survival than patients on conventional dialysis in the first year, many investigators have scrutinized the existing databases to determine the reasons for this apparent difference. It is clear that patients starting on PD are selected – they are younger and have less comorbidity compared to the general population on dialysis. Despite improvements in the morbidities of patients on PD over the past 15 years, the survival of patients on hemodialysis over 5 years is greater than for patients on hemodialysis. The latest analysis points to the considerable survival difference in patients who start dialysis with an arteriovenous fistula or graft compared to patients who start dialysis with a cuffed catheter. Thus, the apparent early survival advantage for patients starting PD can be attributed to selection and comorbidities. Data are emerging that the best survival occurs when patients are dialyzed more frequently than the conventional three times a week. The questions regarding dialysis modality now can shift from whether to encourage PD to how to encourage frequent hemodialysis.