bluuebunny/crossref_metadata_2025 huggingface dataset:
Overexpression of the obesity hormone leptin in human colorectal cancer
Authors: Koda Mariusz , Sulkowska Mariola , Kanczuga-Koda Luiza , Surmacz Eva , Sulkowski Stanislaw
Published: July 2007

Background:Leptin is an adipocyte-derived neurohormone, high levels of which are found in obese individuals. Leptin controls energy expenditure, acting in the brain, and regulates different processes in peripheral organs. Recent studies have suggested that leptin may be involved in cancer development and progression.

Aims:To analyse leptin expression in human colorectal cancer as well as in colorectal mucosa and colorectal adenomas.

Methods:Leptin expression was assessed by immunohistochemistry in 166 colorectal cancers, 101 samples of colorectal mucosa and 41 adenomas. Leptin concentration in colorectal cancer was correlated with selected clinicopathological features.

Results:Immunoreactivity for leptin was observed in 51.2% (85/166) of primary colorectal cancers. In adenomas leptin expression was observed in 14.6% (6/41) of studied cases. In normal mucosa, leptin was present at low levels, except in tumour bordering areas where its concentration appeared to reflect levels in the adjacent cancer tissue. Leptin expression in colorectal cancer significantly correlated with tumour G2 grade (p = 0.002) as well as with histological type (adenocarcinoma) of tumours (p = 0.044).

Conclusions:Results indicate that leptin is overexpressed in human colorectal cancer, which suggests that the hormone might contribute to colorectal cancer development and progression.
MICRO-LAMINATED (ZrO2–Y2O3)/(Al2O3–Y2O3) COATINGS ONFe–25CrALLOY AND THEIR HIGH TEMPERATURE OXIDATION RESISTANCE
Authors: YAO MINGMING , LI FANG , ZHANG YING , HE YEDONG
Published: July 2007

The micro-laminated ( ZrO2– Y2O3)/( Al2O3– Y2O3) composite coatings were prepared on the surface of Fe –25 Cr alloy by an electrochemical process and a sintering process alternately. FE-SEM analyses show that the cross section of the micro-laminated coatings has alternate six-layer films of ZrO2– Y2O3and Al2O3– Y2O3, with the thickness of each layer in the range of nanometer or submicron. The surface of the micro-laminated coatings is composed of nanoparticles. SEM, XRD, and mass gain measurements were adopted to study the oxidation resistance of coatings on the Fe –25 Cr alloy. It has been found that all the coatings are effective in protecting the substrate from oxidation, and micro-laminated coatings exhibit more excellent protectiveness performance, and the oxidation resistance is increased with increasing the layers of the micro-laminated coatings. These beneficial effects can be contributed to the mechanism, by which such a micro-laminated coating synthesizes all the beneficial effects and overcomes all the disadvantages of both the ZrO2– Y2O3coating and the Al2O3– Y2O3coating during the oxidation of the alloy.
TRANSPARENT ZINC OXIDE THIN FILMS PREPARED BY PLD WITH DIFFERENT OXYGEN PRESSURES
Authors: UMA KASIMAYAN , RUSOP MOHAMAD , SOGA TETSUO , JIMBO TAKASHI
Published: July 2007

ZnO thin films were prepared on silicon (001) and corning glass substrates using Pulsed laser deposition (PLD) technique with different oxygen pressures. The microstructure, crystallinity, and resistivity of the films depend on the oxygen pressure used. The effects of the films grown at room temperature and at 500°C with different oxygen pressures have been investigated by analyzing the optical and electrical properties of the film. The XRD analysis showed that the high intensity of c-axis orientation of ZnO thin films was obtained under high oxygen pressure and this leads to greater electrical and optical properties. By applying high pressure oxygen, the resistivity value was decreased and optical transmittance became higher in the visible region. The surface morphology of the films showed that the smooth surface was observed without any cracks.
BORESKOV–HORIUTI–ENOMOTO RULES FOR REVERSIBLE HETEROGENEOUS CATALYTIC REACTIONS
Authors: ZHDANOV VLADIMIR P.
Published: July 2007

In the middle of the previous century, G. K. Boreskov, and J. Horiuti and S. Enomoto independently showed that for reversible reactions, running via a one-route mechanism with a rate-limiting step, there exist general relationships between the reaction rates in the forward and backward directions and also between the corresponding apparent activation energies and reaction heat. Their treatments are formally applicable to gas- and liquid-phase reactions and also to heterogeneous catalytic reactions (HCR) occurring in an ideal overlayer adsorbed on a uniform surface. In reality, HCR often run on heterogeneous surfaces, and the HCR kinetics are complicated by adsorbate–adsorbate lateral interactions. I explicitly demonstrate that in such situations the Boreskov–Horiuti–Enomoto rules are applicable as well.
STABILITY OF COLLOIDAL ALUMINA DISPERSION IN AQUEOUS ALKYL SULFATE SOLUTIONS
Authors: SONG SHAOXIAN , ZHANG YIMIN
Published: July 2007

Coagulation of colloidal alumina in aqueous solutions in the absence or presence of alkyl sulfates has been studied by means of measurements of electrokinetics, adsorption, and coagulate size in this work. The experimental results showed that the coagulation of colloidal alumina in aqueous alkyl sulfate solutions was much stronger than that in aqueous electrolytic solutions. It closely correlated with particle hydrophobicity rendered by the adsorption of alkyl sulfate anions on alumina/water interfaces, indicating hydrophobic coagulation. Also, it has been found that the hydrocarbon chain length of alkyl sulfate strongly influences the hydrophobic coagulation. The longer the chain, the stronger the coagulation and the lower the alkyl sulfate concentration needed for achieving the maximum coagulation degree.
STUDIES OF THE ADSORPTION OF ACETONITRILE (CH3CN) ON Cu(001) USING HELIUM ATOM SCATTERING
Authors: SHUTTLEWORTH I. G.
Published: July 2007

The adsorption of acetonitrile ( CH 3 CN ) on Cu (001) has been studied using elastic Helium atom scattering (HAS) and has been analyzed using a novel method of direct HAS diffraction image inversion. At low temperatures (138 K) acetonitrile permanently adsorbs forming a c(4 × 2) structure at saturation. Annealing the saturated surface to temperatures above 200 K causes the desorption of all surface moieties leaving clean Cu (001). At the adsorption temperatures in the range 153–163 K acetonitrile does not adsorb permanently and demonstrates adsorption–desorption equilibrium. These dynamical studies suggest that the acetonitrile molecule does not dissociate during adsorption. Analyses of the c(4 × 2) HAS diffraction image have revealed several possible surface structures where the C–C–N axis of the adsorbed molecule lies approximately parallel to the Cu (001) surface.
STS INVESTIGATIONS OF METALLIC NANOSTRUCTURES DEPOSITED ON Bi2Te3
Authors: WINIARZ SZYMON , BISKUPSKI PIOTR , SZUBA STANISLAW , MIELCAREK SLAWOMIR , CZAJKA RYSZARD
Published: July 2007

Bi 2 Te 3 has attracted attention due to its potential applications in the microfabrication of integrated thermoelectric devices. It is also interesting to study the metallization process of this compound. Metallic nanostructures were deposited by means of an electron gun evaporator in ultra high vacuum (UHV) conditions (10-8 Pa) on the freshly cleaved 0001 surface of the crystal Bi 2 Te 3. Measurements were conducted using the commercially available Omicron UHV scanning tunneling microscope (STM). Scanning tunneling spectroscopy (STS) measurements were performed using current imaging tunneling spectroscopy (CITS), and subsequent calculation of the dI/dV maps. Metallic characteristics were observed on nickel islands since early stages of the growth. CITS and dI/dV maps showed distinct contrast between the substrate and metallic islands. Similar contrast was not observed in the case of titanium, most probably due to an intercalation process. Occurring of such a process was confirmed by the appearance of the superlattice structure.
A UNIFYING DIFFERENTIAL GAME OF ADVERTISING AND PROMOTIONS
Authors: BENCHEKROUN HASSAN
Published: July 2007

The literature on advertising and promotions can be divided in two categories. A first group of models assume that promotion contributes (positively) to the goodwill towards the product, and a second group assumes that promotions reduce that goodwill. In this paper we build a differential game model where the impact of promotion on goodwill is endogenously determined. We conduct a comparative dynamics exercise. An unexpected result is that an increase in the sensitivity of sales to goodwill can lead to a decrease of the equilibrium level of sales.
PRICING OF RAINBOW OPTIONS: GAME THEORETIC APPROACH
Authors: HUCKI Z. , KOLOKOLTSOV V. N.
Published: July 2007

The general approach for the pricing of rainbow (or colored) options with fixed transaction costs is developed from the game theoretic point of view. The evolution of the underlying common stocks is considered in discrete time. The main result consists in the explicit calculation of the hedge price for a variety of the rainbow options including option delivering the best of J risky assets and cash, calls on the maximum of J risky assets and the multiple-strike options. The results obtained can be also used in the framework of real options.
ON BARGAINING BASED POINT SOLUTION TO COOPERATIVE TU GAMES
Authors: THANGARAJ V. , SUGUMARAN A. , BISWAS AMIT K.
Published: July 2007

Consider the cooperative coalition games with side payments. Bargaining sets are calculated for all possible coalition structures to obtain a collection of imputations rather than single imputation. Our aim is to obtain a single payoff vector, which is acceptable by all players of the game under grand coalition. Though Shapely value is a single imputation, it is based on fair divisions rather than bargaining considerations. So, we present a method to obtain a single imputation based on bargaining considerations.
ERRATUM: "BANKRUPTCY RULES AND COALITIONAL MANIPULATION"
Authors: MORENO-TERNERO JUAN D.
Published: July 2007

In this paper, we study the immunity of bankruptcy rules to manipulation via merging or splitting agents' claims. We focus on the TAL-family of bankruptcy rules (Moreno-Ternero & Villar, 2006), a one-parameter family encompassing three classical rules: the Talmud (T) rule, the constrained equal-awards (A) rule and the constrained equal-losses (L) rule. We show that all rules within the TAL-family are partially non-manipulable and identify the domain of problems where each rule is either non-manipulable by merging or non-manipulable by splitting. We also show that they can be ranked in terms of their relative non-manipulability, according to the parameter that generates the family.
AN ANALYTICAL APPROACH TO BUILDING A TECHNOLOGY DEVELOPMENT ENVELOPE (TDE) FOR ROADMAPPING OF EMERGING TECHNOLOGIES
Authors: GERDSRI N.
Published: July 2007

This paper presents the research on the development of a new concept and methodology called Technology Development Envelope (TDE). The TDE approach is applied to identify the optimum path in developing a technology roadmap in which the company's technology strategies and business strategies are combined. TDE allows the executive level decision makers in corporations, as well as the policy level decision makers in governments to incorporate emerging technologies into the development of technology strategies. The combination of Delphi method and Hierarchical Decision Modeling (HDM) is used as a foundation for building the TDE concept. The judgments from technology developers and technology implementers are utilized in the process to ensure that the technology strategies are in full support of corporate goals and objectives.
USING TRIZ AND AXIOMATIC DESIGN SYNERGISTICALLY: A CASE STUDY
Authors: SHIRWAIKER ROHAN A. , OKUDAN GÜL E.
Published: July 2007

With increasing global competition, expediting the problem solving process has become crucial in the industry. Techniques such as Theory of Inventive Problem Solving (TRIZ) and Axiomatic Design (AD) have been widely applied for this purpose. TRIZ and AD are very powerful tools with different but complementary strengths. A previously proposed synergistic approach based on TRIZ and AD enhances the individual strengths of these methods by using them within a common framework, thus providing a more powerful methodology for problem solving. In this paper, we demonstrate the effectiveness of the synergistic approach through a manufacturing related case-study. Considering the importance of validation of engineering models, a validation method for the synergistic approach is discussed based on review of design engineering validation literature.
TECHNOLOGY FUTURES ANALYSIS METHODOLOGIES FOR SUSTAINABLE ENERGY TECHNOLOGIES
Authors: PHILLIPS JOANNE G. , HEIDRICK TED R. , POTTER IAN J.
Published: July 2007

Futures Analysis Methodologies are reviewed and assessed to determine the most appropriate methodology for assessing the future value of a current investment in a sustainable energy technology. Assessment criteria are defined and each method is evaluated against these criteria. The paper provides preliminary conclusions regarding which methodologies to pursue for the purpose of developing a model to predict the future value of a current energy/environmental technology.
CREATIVITY ENGINEERING FOR CONTINUOUS AND DISCONTINUOUS INNOVATION
Authors: LIN JUSTIN J. Y.
Published: July 2007

Concurrent engineering (CE) has been widely implemented in many industries so that developers can consider all elements of the product lifecycle during the product design phase. However, although concurrent engineering is a very effective approach for product design team-up, it does not help to generate new product concepts. To build a successful innovation model, research has investigated how concurrent engineering can be extended to a new concept which covers not only the downstream phase from design concept to the entire product design process, but also the upstream phase from brainstorming to the generation process of new product concepts. Results show that a product knowledge and innovation (PKI) system based on the concepts of creativity engineering (CE-II), which is extended from the current practice of concurrent engineering, can be used to achieve the goals for both continuous and fusion-type discontinuous innovation.
SELF-ORGANIZED DISTRIBUTION OF EXTREMELY SMALL Ti QUANTUM DOTS IN SiO2
Authors: RABALAIS J. W. , ZHAO J. P. , HUANG D. X. , CHU W. K.
Published: July 2007

Self-organized extremely small Ti nanodots have been formed in the subsurface of SiO 2 by implantation of isotopic 48 Ti + at a kinetic energy of 9 keV into (0001) Z-cut quartz, followed by a vacuum annealing process. Transmission electron microscopy (TEM) images show that the Ti nanodots have a two-dimensional distribution, i.e., a uniform size as small as 3.8 nm and relatively uniform positions with nearly constant inter-particle spacing of ~ 1.5 nm. A mechanism for the two-dimensional spatial distribution and the inhibition of chemical reactions between Ti and SiO 2 is discussed.
CONTINUUM MODELING OF INTERFACES IN POLYMER MATRIX COMPOSITES REINFORCED BY CARBON NANOTUBES
Authors: JIANG LIYING , TAN HONGLAI , WU JIAN , HUANG YONGGANG , HWANG KEH-CHIH
Published: July 2007

The interface behavior may significantly influence the mechanical properties of carbon nanotube (CNT)-reinforced composites due to the large interface area per unit volume at the composite. The modeling of CNT/polymer interfaces has been a challenge in the continuum modeling of CNT-reinforced composites. This paper presents a review of recent progress to model the CNT/matrix interfaces via a cohesive law established from the van der Waals force. A simple, analytical cohesive law is obtained from the inter-atomic potential, and is used to study the effect of CNT/matrix interfaces on the macroscopic properties of CNT-reinforced composites.
Performance Limitations of Si Bulk CMOS and Alternatives for future ULSI
Authors: Saraswat Krishna C. , Kim Donghyun , Krishnamohan Tejas , Pethe Abhijit
Published: July 2007

A channel material with high mobility and therefore high injection velocity can increase on current and reduce delay. Currently, strained-Si is the dominant technology for high performance MOSFETs and increasing the strain provides a viable solution to scaling. However, looking into future scaling of nanoscale MOSFETs it becomes important to look at higher mobility materials, like Ge and III-V materials together with innovative device structures which may perform better than even very highly strained Si. For both Ge and III-V devices problems of leakage need to be solved. Novel heterostructures will be needed to exploit the promised advantages of Ge and III-V based devices.
The Small Differences between 45nm and 45 inches
Authors: Reita Carlo
Published: July 2007

In this paper will be illustrated the parallel development path between the TFT and ULSI fields focusing in particular on the common/equivalent issues which must be dealt with in both fields. The basis are essentially the economic drivers which impose the development frame, the challenges in the lithography to keep up with the patterning requirements, and the problems in the materials development and their integration in a viable production environment .
Device Performance and Reliability of Fully Developed SOI Transistors and Low-Temperature Poly-Si TFTs
Authors: Matsumura Mieko , Hatano Mutsuko , Hamamura Hirotaka , Mitsuharu Tai , Toyota Yoshiaki , Ohkura Makoto
Published: July 2007

The device performance and reliability of the SOI TFTs and the LTPS-TFTs were compared. Changing channel material from single-crystal Si to ELA poly-Si reduces mobility by 75%, and changing gate oxide material from thermal oxide to CVD oxide enhances current degradation due to hot carrier stress by almost ten times. To improve performance, selectively enlarging laser crystallization (SELAX) process which realizes poly-Si films with large grain and smooth surface has been developed. The mobility of SELAX-TFTs is twice of conventional LTPS-TFTs. To fabricate high quality interfacial layer at the interface between the gate oxide layers and the channel layers, cyclic deposition with O2 plasma treatment (C-DOP) process has been also developed. The lifetime of hot carrier degradation was extended by tenth using the C-DOP process.
ULSIC vs. TFT - What Can They Learn from Each Other?
Authors: Kuo Yue
Published: July 2007

MOSFETs and TFTs have the similar technology growth path but different product application areas. Although the TFT manufacturing process was derived from the ULSIC process, its unique low-temperature, large-area technology development experience could greatly benefit the future large-wafer ULSIC production. The author discussed issues on processes, materials, devices, and applications with examples. In the future, although ULSIC and TFT will grow in different directions, they can be complimentary to each other or even be integrated into the same product in some cases.
Improvement of Silicon-Based Thin Film Transistor Performances by Modifying Technological Fabrication Process Steps: a Similar Approach with ULSI Technology
Authors: Bonnaud Olivier , Mohammed-Brahim Tayeb
Published: July 2007

The silicon based thin film transistors technological process evolution is governed by electrical performance improvements that are needed for the numerous fields of large area electronic applications. In fact, the electrical properties of the TFTs are directly linked to many aspects combining efforts to improve the process steps by several ways. All these approaches are similar to the ultra large scale integration technology (ULSI) ones. The goal of this paper is to highlight these similarities. After the presentation of the evolution during the last twenty years of the TFT processes, we will discuss on the common approaches between nano- and giga- electronics in order to show that their basic scientific principles are roughly the same.
CPU for HF and UHF Operation on the Glass and Flexible Substrates
Authors: Koyama Jun , Kurokawa Yoshiyuki , Ikeda Takayuki , Endo Masami , Dembo Hiroki , Kawae Daisuke , Inoue Takayuki , Kozuma Munehiro , Ohgarane Daisuke , Saito Satoru , Dairiki Koji , Takahashi Hidekazu , Yamazaki Shunpei
Published: July 2007

In 2005, we developed the first 13.56 MHz flexible RFCPU (8 bit) in the world by the flexible LSI (LSI on plastic) manufacturing technology, which is based on the manufacturing technology of LSI on glass and the peeling and transferring technology. In 2006, we considered the possibility of realizing a UHF RFCPU (8 bit) using a radio signal in the UHF band (915 MHz). A radio signal in the UHF band is in principle more capable of long distance communication than the 13.56 MHz radio signal. In this paper, we will report the results of test producing the high-performance 13.56 MHz (HF) RFCPU and UHF RFCPU, as an examination of the potential of the high-function RFCPU by the glass LSI manufacturing process and the flexible LSI manufacturing process.
Verase Improvement for Split-gate Embedded Flash Through Poly Grain Size Reduction
Authors: Ng Hong Seng , Tan Hong Mui
Published: July 2007

0.25µm embedded flash device has been built using combination of the SST Split-gate [1] memory cell design and standard CMOS process technology. Several areas of process development have been put in to meet the customer erase voltage (Verase) and endurance specification. In this paper, the focus is on the floating gate polysilicon process optimization. The poly tip of floating gate is sharpened by grain size reduction. The Verase has been successfully reduced by at least 0.4V, attaining endurance cycle of more than 100k
High and Low Stress Voltage Instabilities in High-K Gate Stacks
Authors: Bersuker Gennadi , Young Chad , Heh Dawei , Choi Rino , Lee Byoung H. , Jammy Raj
Published: July 2007

Accelerated high voltage stress traditionally employed for reliability assessments of SiO2 gate dielectrics was found to cause degradation of the high-k gate stacks, which may not reflect the dielectric wear-out under the device operating conditions. It is shown that high voltage stress activates trap generation in both HfO2 high-k dielectric and interfacial SiO2 layer (IL), which was not observed under low stress voltages. At lower stress voltages of practical interest, the gate stack degradation is dominated by trap generation in IL. In the case of nMOSFETs, in particular, this trap generation occurs at the pre-existing (induced by the interaction with the high-k dielectric) defect precursor sites.
Spectroscopic Studies of Band Edge Electronic and Defect States in Elemental High-k Oxide Dielectrics and Si Oxynitride Alloys onto Si(100) Substrates
Authors: Lucovsky Gerald , Seo Hyungtak , Fleming Les , Ulrich Marc , Lüning Jan
Published: July 2007

This paper applies near edge X-ray absorption spectroscopy (NEXAS) and soft-X-ray photoelectron spectroscopy (SXPS) to identity different length scales of nano-crystallinity in transition metal (TM) elemental oxides. Jahn-Teller (J-T) splittings in band edge HfO2 Eg states in O K1 NEXAS spectra requires nano-crystalline grain-sizes >3 to 4 nm and coherent p-bonding interactions. The spectroscopic studies provide an unambiguous way to distinguish between two regimes of nano-crystalline order with coherent and incoherent p-bonding interactions, yielding significant information on band edge electronic structure, and electronically active defects as well. Finally, defects in non-crystalline Hf Si oxynitride alloys are shown to be qualitatively different than those in either the nano-crystalline scale regimes.
InN Nanostructured Materials: Controlled Synthesis, Characterizations, and Applications
Authors: Mangum Josh , Kryliouk Olga , Park H J. , Anderson T J. , Liliental-Weber Z
Published: July 2007

InN 1D materials were successfully grown by metal-organic vapor phase epitaxy (MOVPE) and non-catalytic, template-free hydride metal-organic vapor phase epitaxy (H-MOVPE) on Si, GaN, and c-Al2O3 substrates. Dislocation-free, high-quality InN nanorods with [00.1] growth axis were formed via an apparent vapor-solid (VS) growth mechanism by H-MOVPE. On a contrary when conventional MOVPE was employed InN nanowires were grown via vapor-liquid-solid (VLS) mechanism. The controlled growth of self-seeded III-Nitride nanostructured materials has been demonstrated.
Nanostructure and Morphology of Electrodeposited Copper Metallization during Room-Temperature Aging
Authors: Buckley Denis N. , Ahmed Shafaat , Ahmed Tanjim T. , Nakahara Shohei
Published: July 2007

We describe the phenomenon of spontaneous morphology change (SMC) observed during room temperature aging of electrodeposited copper metallization after an incubation period. We discuss AFM observations and the use of isothermal annealing experiments to estimate an activation energy for the recovery (incubation) process. The results are compared with corresponding DSC measurements. A model for SMC is presented.
Modeling Of Thin Film Transistors with Non-Ideal Contacts
Authors: Shur Michael , Veksler D. , Chivikula V. , Koudymov A. , Ytterdal T. , Iñiguez B. , Jackson W.
Published: July 2007

We describe the compact model that captures the new physics involved in Thin Film Transistors with non-ideal contacts, where the contact itself controls the carrier density under the contact. Such a contact could be modeled as a non-linear transmission line consisting of thin film transistors with leaky gates. However, we show that the compact model that incorporates a contact thin film transistor and non-ideal diodes can adequately describe experimental data, such as dependencies of field effect mobility on the gate length for different materials systems ranging from amorphous silicon to organic semiconductors. The model can also describe the capacitance-voltage characteristics and suitable for implementation in circuit simulators, such as AIM-Spice.
Transparent OTFTs with Color-Filtering Functional Gate Insulators
Authors: Chuang Chiao-Shun , Chen Fang-Chung , Shieh Han-Ping D.
Published: July 2007

We have developed color-filtering functional organic thin-film transistors (OTFTs) exhibiting high field-effect mobility (0.35 cm2/Vs), large on/off current ratio (>105) and CIE 1931 chromaticity (0.64, 0.34), (0.36, 0.54) or (0.14, 0.15). The conventional colorant inks were utilized as color filter/dielectric layer of the OTFTs to obtain desired colors. In order to improve the performance of color filtering OTFTs, a new high dielectric constant polymeric insulator named F3 was firstly introduced to be a modification layer upon colorant ink layers, resulting in optimized optical properties and electrical performance. This work was successfully integrated gate insulator and color filter, which offered an ink-jet printing compatible process for cost-effective fabrication of liquid-crystal displays. In addition, light sensitivity of OTFTs was significantly reduced after introducing TiO2 nanoparticles blended into gate insulator.
Intelligent Pixel Architectures for Digital Medical Imaging Applications
Authors: Karim Karim S. , Izadi Mohammed Hadi , Taghibakhsh Farhad , Sanaie Golnaz
Published: July 2007

The most widely used architecture in large area amorphous silicon (a-Si) flat panel imagers is a passive pixel sensor (PPS), which consists of a detector and a readout switch. While the PPS has the advantage of being compact and amenable towards high-resolution imaging, reading small PPS output signals requires external column charge amplifiers that produce additional noise and reduce the minimum readable sensor input signal. This work presents current mediated amorphous silicon active pixel readout circuits based on four, three and two transistor designs that perform on-pixel amplification of noise-vulnerable sensor input signals to minimize the effect of external readout noise sources associated with "off-chip" charge amplifiers. The on-pixel amplifiers appear promising for use in fast readout, noise-sensitive, large area, digital medical imaging applications such as dual mode radiography/fluoroscopy and mammography tomosynthesis.
Efficacy of an inhibitor of adhesion molecule expression (GI270384X) in the treatment of experimental colitis
Authors: Panés Julián , Aceituno Montserrat , Gil Fèlix , Miquel Rosa , Piqué Josep M , Salas Azucena , McLean Peter
Published: July 2007

Modulation of adhesion molecule expression or function is regarded as a promising therapy for inflammatory conditions. This study evaluates the effects of an inhibitor of adhesion molecule expression (GI270384X) in two experimental models of colitis. Colitis of different severity was induced in C57BL/6J mice by administering 1, 2, or 3% dextran sulfate sodium (DSS). GI270384X (3, 10, or 25 mg·kg−1·day−1) was administered as pretreatment or started 3 days after colitis induction. In IL-10-deficient mice, the highest dose was given for 2 wk. The clinical course of colitis, pathological changes, serum inflammatory biomarkers, expression of adhesion molecules, and leukocyte-endothelial cell interactions in colonic venules were measured in mice treated with vehicle or with active drug. In the most severe forms of colitis (2% and 3% DSS and IL-10-deficient mice), the magnitude of colonic inflammation was not modified by treatment with GI270384X. In a less severe form of colitis (1% DSS), GI270384X treatment dose dependently ameliorated the clinical signs of colitis, colonic pathological changes, and serum levels of biomarkers (IL-6 and serum amyloid A). Administration of 25 mg·kg−1·day−1GI270384X abrogated upregulation of ICAM-1 in the inflamed colon but had no effect on VCAM-1 or E-selectin expression. This was associated with a significant reduction in number of rolling and firmly adherent leukocytes in colonic venules. These results indicate that GI270384X is effective in the treatment of experimental colitis of moderate severity. Reduced adhesion molecule expression and leukocyte recruitment to the inflamed intestine contribute to this beneficial effect.
Hepatic leukocyte recruitment in response to time-limited expression of TNF-α and IL-1β
Authors: Patrick Amanda L. , Rullo Jacob , Beaudin Suzanne , Liaw Patricia , Fox-Robichaud Alison E.
Published: July 2007

The development of chronic liver diseases is mediated by sustained hepatic inflammation. Our objective was to characterize the molecular mechanisms responsible for the hepatic inflammatory response to time-limited TNF-α and IL-1β expression. C57Bl/6 mice were injected with 2 × 107plaque forming units intraperitoneally of an adenoviral vector containing TNF-α or IL-1β (AdTNF-α or AdIL-1β). A nonreplicating adenoviral vector served as control. Four days later, under ketamine and xylazine anesthesia, the liver microvasculature was examined by intravital microscopy. In the postsinusoidal venules, leukocyte rolling increased significantly in response to both AdTNF-α and AdIL-1β, compared with controls. This response was significantly reduced following injection of an anti-α4-integrin monoclonal antibody (MAb). Postsinusoidal rolling was further reduced to baseline following injection of an anti-P-selectin or anti-L-selectin MAb. Sinusoidal adhesion was greater in mice treated with AdIL-1β than with AdTNF-α. Blocking α4-integrin, P-selectin, or L-selectin had no significant effect on sinusoidal or postsinusoidal adhesion. In separate experiments, we administered AdTNF-α or AdIL-1β to mice deficient in ICAM-1. In ICAM-1−/− mice, postsinusoidal leukocyte rolling significantly increased following expression of IL-1β but not TNF-α. AdIL-1β- but not AdTNF-α-mediated sinusoidal adhesion was ICAM-1 dependent. AdTNF-α-induced sinusoidal adhesion was significantly reduced following 4 days of anti-MIP-2 MAb and anti-KC MAb. Prolonged expression of the cytokines TNF-α and IL-1β increases hepatic leukocyte-endothelial cell interactions. Interestingly, the mechanisms through which these cytokines bring about adhesion within the sinusoids differ; AdIL-1β sinusoidal adhesion uses an ICAM-1-dependent mechanism whereas AdTNF-α-mediated adhesion is ICAM-1 independent but CXC chemokine dependent.
Characterization of protein kinase pathways responsible for Ca2+sensitization in rat ileal longitudinal smooth muscle
Authors: Ihara Eikichi , Moffat Lori , Ostrander Janina , Walsh Michael P. , MacDonald Justin A.
Published: July 2007

We investigated the protein kinases responsible for myosin regulatory light chain (LC20) phosphorylation and regulation of myosin light chain phosphatase (MLCP) activity during microcystin (phosphatase inhibitor)-induced contraction at low Ca2+concentrations of rat ileal smooth muscle stretched in the longitudinal axis. Application of 1 μM microcystin induced LC20diphosphorylation and contraction of β-escin-permeabilized rat ileal smooth muscle at pCa 9. The PKC inhibitor GF-109203x, the MEK inhibitor PD-98059, and the p38 MAPK inhibitor SB-203580 significantly reduced this contraction. These inhibitory effects were abolished when the microcystin concentration was increased to 10 μM, indicating that application of these kinase inhibitors generated an increase in MLCP activity. GF-109203x and PD-98059, but not SB-203580, significantly decreased the phosphorylation level of the myosin-targeting subunit of MLCP, MYPT1, at Thr-697 (rat sequence) during microcystin-induced contraction at pCa 9. On the other hand, SB-203580, but not GF-109203x or PD-98059, significantly reduced the phosphorylation level of the PKC-potentiated phosphatase inhibitor of 17 kDa (CPI-17). A zipper-interacting protein kinase (ZIPK) inhibitor (SM1 peptide) and a Rho-associated kinase inhibitor (Y-27632) had little effect on microcystin-induced contraction at pCa 9. In conclusion, PKC, ERK1/2, and p38 MAPK pathways facilitate microcystin-induced contraction at low Ca2+concentrations by contributing to the inhibition of MLCP activity either through phosphorylation of MYPT1 or CPI-17 [probably mediated by integrin-linked kinase (ILK)]. ILK and not ZIPK is likely to be the protein kinase responsible for LC20diphosphorylation during microcystin-induced contraction of rat ileal smooth muscle at pCa 9, similar to its recently described role in vascular smooth muscle. The negative regulation of MLCP by PKC and MAPKs during microcystin-induced contraction at pCa 9, which is not observed in vascular smooth muscle, may be unique to phasic smooth muscle.
Insulin, leptin, and adiponectin receptors in colon: regulation relative to differing body adiposity independent of diet and in response to dimethylhydrazine
Authors: Drew Janice E. , Farquharson Andrew J. , Padidar Sara , Duthie Garry G. , Mercer Julian G. , Arthur John R. , Morrice Philip C. , Barrera Lawrence N.
Published: July 2007

Obesity has recently become a focus of research to elucidate diet and lifestyle factors as important risk factors for colon cancer. Altered levels of insulin, leptin, and adiponectin have been identified as potential candidates increasing colon cancer risk within the prevailing obesogenic environment. There has been considerable research to characterize signaling via these hormones in the brain, liver, and adipose tissue; however, very little is known of their emerging role in peripheral signaling, particularly in epithelial tissues. This study profiles insulin, leptin, and adipokine receptors in the rat colon, revealing novel microanatomical location of these receptors and thereby supporting a potential role in regulating colonic tissue. Potential involvement of insulin, leptin, and adiponectin receptors in increased risk of colon cancer was investigated using Sprague-Dawley rats, either resistant or susceptible to diet-induced obesity. Regulation of insulin, leptin, and adiponectin receptors as a consequence of differing levels of adiposity was assessed regionally in the colon in response to treatment with the chemical carcinogen 1,2-dimethylhydrazine (DMH). However, significantly increased fat mass, increased levels of plasma insulin, leptin, and triglycerides, previously associated with an increased risk of colon cancer, were not associated with promotion of precancerous lesions in the experimental rats or deregulation of insulin, leptin, or adiponectin receptors. These findings do not support a direct link between the deregulation of insulin and adipokine levels observed in obese rats and an increased risk of colon carcinogenesis.
Calcitonin gene-related peptide-evoked sustained tachycardia in calcitonin receptor-like receptor transgenic mice is mediated by sympathetic activity
Authors: Kunz Thomas H. , Scott Michelle , Ittner Lars M. , Fischer Jan A. , Born Walter , Vogel Johannes
Published: July 2007

Calcitonin gene-related peptide (CGRP) and adrenomedullin (AM) are potent vasodilators and exert positive chronotropic and inotropic effects on the heart. Receptors for CGRP and AM are calcitonin receptor-like receptor (CLR)/receptor-activity-modifying protein (RAMP) 1 and CLR/RAMP2 heterodimers, respectively. The present study was designed to delineate distinct cardiovascular effects of CGRP and AM. Thus a V5-tagged rat CLR was expressed in transgenic mice in the vascular musculature, a recognized target of CGRP. Interestingly, basal arterial pressure and heart rate were indistinguishable in transgenic mice and in control littermates. Moreover, intravenous injection of 2 nmol/kg CGRP, unlike 2 nmol/kg AM, decreased arterial pressure equally by 18 ± 5 mmHg in transgenic and control animals. But the concomitant increase in heart rate evoked by CGRP was 3.7 times higher in transgenic mice than in control animals. The effects of CGRP in transgenic and control mice, different from a decrease in arterial pressure in response to 20 nmol/kg AM, were suppressed by 2 μmol/kg of the CGRP antagonist CGRP(8-37). Propranolol, in contrast to hexamethonium, blocked the CGRP-evoked increase in heart rate in both transgenic and control animals. This was consistent with the immunohistochemical localization of the V5-tagged CLR in the superior cervical ganglion of transgenic mice. In conclusion, hypotension evoked by CGRP in transgenic and control mice was comparable and CGRP was more potent than AM. Unexpectedly, the CLR/RAMP CGRP receptor overexpressed in postganglionic sympathetic neurons of transgenic mice enhanced the positive chronotropic action of systemic CGRP.
Genetic and environmental influences on skeletal muscle phenotypes as a function of age and sex in large, multigenerational families of African heritage
Authors: Prior Steven J. , Roth Stephen M. , Wang Xiaojing , Kammerer Candace , Miljkovic-Gacic Iva , Bunker Clareann H. , Wheeler Victor W. , Patrick Alan L. , Zmuda Joseph M.
Published: July 2007

The aim of this study was to estimate the heritability of and environmental contributions to skeletal muscle phenotypes (appendicular lean mass and calf muscle cross-sectional area) in subjects of African descent and to determine whether heritability estimates are impacted by sex or age. Body composition was measured by dual-energy X-ray absorptiometry and computed tomography in 444 men and women aged 18 yr and older (mean: 43 yr) from eight large, multigenerational Afro-Caribbean families (family size range: 21–112). Using quantitative genetic methods, we estimated heritability and the association of anthropometric, lifestyle, and medical variables with skeletal muscle phenotypes. In the overall group, we estimated the heritability of lean mass and calf muscle cross-sectional area (h2 = 0.18–0.23, P < 0.01) and contribution of environmental factors to these phenotypes ( r2 = 0.27–0.55, P < 0.05). In our age-specific analysis, the heritability of leg lean mass was lower in older vs. younger individuals (h2 = 0.05 vs. 0.23, respectively, P = 0.1). Sex was a significant covariate in our models ( P < 0.001), although sex-specific differences in heritability varied depending on the lean mass phenotype analyzed. High genetic correlations (ρG = 0.69–0.81; P < 0.01) between different lean mass measures suggest these traits share a large proportion of genetic components. Our results demonstrate the heritability of skeletal muscle traits in individuals of African heritage and that heritability may differ as a function of sex and age. As the loss of skeletal muscle mass is related to metabolic abnormalities, disability, and mortality in older individuals, further research is warranted to identify specific genetic loci that contribute to these traits in general and in a sex- and age-specific manner.
Relationship between resting ventilatory chemosensitivity and maximal oxygen uptake in moderate hypobaric hypoxia
Authors: Ogawa Takeshi , Hayashi Keiji , Ichinose Masashi , Nishiyasu Takeshi
Published: July 2007

This study tested the hypothesis that the extent of the decrement in V̇o2max and the respiratory response seen during maximal exercise in moderate hypobaric hypoxia (H; simulated 2,500 m) is affected by the hypoxia ventilatory and hypercapnia ventilatory responses (HVR and HCVR, respectively). Twenty men (5 untrained subjects, 7 long distance runners, 8 middle distance runners) performed incremental exhaustive running tests in H and normobaric normoxia (N) condition. During the running test, V̇o2, pulmonary ventilation (V̇e) and arterial oxyhemoglobin saturation (SaO2) were measured, and in two ventilatory response tests performed during N, a rebreathing method was used to evaluate HVR and HCVR. Mean HVR and HCVR were 0.36 ± 0.04 and 2.11 ± 0.2 l·min−1·mmHg−1, respectively. HVR correlated significantly with the percent decrements in V̇o2max (%dV̇o2max), SaO2 [%dSaO2 = (N−H)·N−1·100], and V̇e/V̇o2 seen during H condition. By contrast, HCVR did not correlate with any of the variables tested. The increment in maximal V̇e between H and N significantly correlated with %dV̇o2max. Our findings suggest that O2 chemosensitivity plays a significant role in determining the level of exercise hyperventilation during moderate hypoxia; thus, a higher O2 chemosensitivity was associated with a smaller drop in V̇o2max and SaO2 under those conditions.
The ontogeny of hemodynamic responses to prolonged umbilical cord occlusion in fetal sheep
Authors: Wassink Guido , Bennet Laura , Booth Lindsea C. , Jensen Ellen C. , Wibbens Bert , Dean Justin M. , Gunn Alistair Jan
Published: July 2007

There is evidence that preterm fetuses have blunted chemoreflex-mediated responses to hypoxia. However, the preterm fetus has much lower aerobic requirements than at term, and so moderate hypoxia may not be sufficient to elicit maximal chemoreflex responses; there are only limited quantitative data on the ontogeny of chemoreflex and hemodynamic responses to severe asphyxia. Chronically instrumented fetal sheep at 0.6 ( n = 12), 0.7 ( n = 12), and 0.85 ( n = 8) of gestational age (GA; term = 147 days) were exposed to 30, 25, or 15 min of complete umbilical cord occlusion, respectively. At all ages, occlusion was associated with early onset of bradycardia, profoundly reduced femoral blood flow and conductance, and hypertension. The 0.6-GA fetuses showed a significantly slower and lesser fall in femoral blood flow and conductance compared with the 0.85-GA group, with a correspondingly reduced relative rise in mean arterial blood pressure. As occlusion continued, the initial adaptation was followed by loss of peripheral vasoconstriction and progressive development of hypotension in all groups. The 0.85-GA fetuses showed significantly more sustained reduction in femoral conductance but also more rapid onset of hypotension than either of the younger groups. Electroencephalographic (EEG) activity was suppressed during occlusion in all groups, but the degree of suppression was less at 0.6 GA than at term. In conclusion, the near-midgestation fetus shows attenuated initial (chemoreflex) peripheral vasomotor responses to severe asphyxia compared with more mature fetuses but more sustained hemodynamic adaptation and reduced suppression of EEG activity during continued occlusion of the umbilical cord.
Practicable approaches to facilitate rapid and accurate molecular cytogenetic mapping in birds and mammals
Authors: Morris W.B. , Stephenson J.E. , Robertson L.B.W. , Turner K. , Brown H. , Ioannou D. , Tempest H.G. , Skinner B.M. , Griffin D.K.
Published: July 2007

Molecular cytogenetic mapping by FISH is a common feature of most genome projects as it provides a global, low-resolution overview of the genome and facilitates comparative genomics. An essential prerequisite for cytogenetic mapping is the ability to identify accurately the chromosome on which the clone (e.g. BAC) resides. This is not usually a barrier to human mapping as knowledge of the human karyotype is commonplace. For other species however accurate assignment can be problematic either because, as in birds, the karyotype is too complex to analyze by standard means or because of the paucity of individuals skilled to perform the karyotyping. Using chicken as a model we have developed a reproducible approach for accurate cytogenetic mapping that involves: a single colour FISH, measurement of the ratio of the size of the signal bearing chromosome to that of chromosome 8, and final assignment through a small series of dual colour experiments. Reference values for size ratios were established using base pair estimate information from the Ensembl browser. By this method cytogenetic mapping to highly complex karyotypes can be achieved in a small number of simple steps. We have also developed and tested a karyotyping tutorial programme adapted from one previously reported in this journal. That is, we have used pig as an example of a model species with a relatively tractable karyotype and demonstrated that scientists and students, even after only one hour using our tutorial, can readily identify pig chromosomes and thus make appropriate assignments using FISH. Simple, practicable means often provide preferable solutions than complex alternatives (e.g. m-FISH) to the solution of scientific problems. Such is the case for the approaches described here.
The evolution of the avian genome as revealed by comparative molecular cytogenetics
Authors: Griffin D.K. , Robertson L.B.W , Tempest H.G. , Skinner B.M.
Published: July 2007

Birds are characterised by feathers, flight, a small genome and a very distinctive karyotype. Despite the large numbers of chromosomes, the diploid count of 2n ≈ 80 has remained remarkably constant with 63% of birds where 2n = 74–86, 24% with 2n = 66–74 and extremes of 2n = 40 and 2n = 142. Of these, the most studied is the chicken (2n = 78), and molecular cytogenetic probes generated from this species have been used to further understand the evolution of the avian genome. The ancestral karyotype is, it appears, very similar to that of the chicken, with chicken chromosomes 1, 2, 3, 4q, 5, 6, 7, 8, 9, 4p and Z representing the ancestral avian chromosomes 1–10 + Z; chromosome 4 being the most ancient. Avian evolution occurred primarily in three stages: the divergence of the group represented by extant ratites (emu, ostrich etc.) from the rest; divergence of the Galloanserae (chicken, turkey, duck, goose etc.) – the most studied group; and divergence of the ‘land’ and ‘water’ higher birds. Other than sex chromosome differentiation in the first divergence there are no specific changes associated with any of these evolutionary milestones although certain families and orders have undergone multiple fusions (and some fissions), which has reduced their chromosome number; the Falconiformes are the best described. Most changes, overall, seem to involve chromosomes 1, 2, 4, 10 and Z where the Z changes are intrachromosomal; there are also some recurring (convergent) events. Of these, the most puzzling involves chromosomes 4 and 10, which appear to have undergone multiple fissions and/or fusions throughout evolution – three possible hypotheses are presented to explain the findings. We conclude by speculating as to the reasons for the strange behaviour of these chromosomes as well as the role of telomeres and nuclear organisation in avian evolution.