bluuebunny/crossref_metadata_2025 huggingface dataset:
Altering the surface area available for transport of calcium from the eggshell does not affect calcium metabolism of chicken embryos
Authors: Packard Mary J.
Published: August 2008

The amount of contact between the chorionic surface of the chorioallantoic membrane and the inner aspect of the eggshell was reduced by causing formation of an extra air cell in chicken eggs on day 8 of incubation. This manipulation reduced the surface area available for transport of calcium from the eggshell to the embryo. Concentrations of calcium, magnesium, and phosphorus in serum were determined for embryos sampled on days 12, 15, and 18, and for hatchlings. Calcium, magnesium, and phosphorus content of residual yolks and yolk-free carcasses of hatchlings was also determined. The presence of an extra air cell did not lead to variation in any of these indices of calcium metabolism. One interpretation of these results is that embryos compensate for the reduction in surface area available for transport of calcium by increasing the transport of calcium across those areas of the chorioallantois that remain in contact with the eggshell.
Reproduction and nutrient reserves of bushy-tailed wood rats (Neotoma cinerea)
Authors: Hickling Graham J. , Millar John S. , Moses Richard A.
Published: August 2008

Body composition and energy content of female bushy-tailed wood rats (Neotoma cinerea) were examined in relation to reproductive status. We assessed the extent to which nutrients for offspring were obtained from endogenous reserves, and whether use of these reserves might influence the timing of spring breeding. Among breeding females, fat levels were highest during pregnancy, and were depleted during lactation. The mean reduction in energy content from pregnancy through lactation (266 kJ) accounted for 21% of the estimated 1260 kJ contributed by a female to her offspring in this period. Females potentially gained 3.0 days of nutritional support from their endogenous reserves during winter, but this fell to 2.0 days during summer and was only 0.8 days during lactation. Thus, females support the nutritional demands of lactation primarily by increasing their ingestion of food. Nevertheless, large endogenous reserves may enable some females to begin breeding early in the spring, when the abundance of food is unpredictable.
Trends in North American small mammals found in common barn-owl (Tyto alba) dietary studies
Authors: Clark Jr. Donald R. , Bunck Christine M.
Published: August 2008

Data on mammals were compiled from published studies of common barn-owl (Tyto alba) pellets. Mammalian composition of pellet samples was analyzed within geographic regions in regard to year, mean annual precipitation, latitude, and number of individual mammals in the sample. Percentages of individuals in pellets that were shrews increased whereas the percentages of rodents decreased with greater mean annual precipitation, especially in northern and western areas of North America. From the 1920s through 1980s, in northern and eastern areas the percentage of species that was shrews decreased, and in northern and central areas the percentage of individuals that was murid rats and mice increased. Human alterations of habitats during these seven decades are postulated to have caused changes in available small mammals, leading to changes in the barn-owl diet.
INFORMATION GEOMETRY, INFERENCE METHODS AND CHAOTIC ENERGY LEVELS STATISTICS
Authors: CAFARO CARLO
Published: August 2008

In this letter, we propose a novel information-geometric characterization of chaotic (integrable) energy level statistics of a quantum antiferromagnetic Ising spin chain in a tilted (transverse) external magnetic field. Finally, we conjecture our results might find some potential physical applications in quantum energy level statistics.
CHAOTIC CONTROL OF LOGISTIC MAP
Authors: WANG XINGYUAN , WANG MINGJUN
Published: August 2008

With the occasional feedback method, the chaotic logistic map is stabilized at an unstable low-periodic orbit. In our method, the qualified feedback coefficient can be obtained through calculation instead of through simulation. Besides, the bifurcation control of the logistic map is studied, and a new scheme is proposed to change the parameter value of any one bifurcation point of this dynamic system optionally. Simulation results show the effectiveness of the methods.
TEMPERATURE DEPENDENCE OF PHOTOINDUCED ANISOTROPY IN THE PHOTOCONDUCTIVITY OF As2Se3 AND Sb2S3 THIN FILMS
Authors: ATAK K. , AKTAŞ G. , SKARLATOS Y. , INCI M. N.
Published: August 2008

The temperature dependence of photoinduced anisotropy in the photoconductivity of As 2 Se 3 and Sb 2 S 3 thin films was investigated, in the interval between -50 and 70°C. Our results demonstrate that for both As 2 Se 3 and Sb 2 S 3 thin films, the anisotropy percentage falls with increasing temperature. We surmise that the aligning effect of the linearly polarized light was diluted with increasing temperature, because the latter induces similar mechanisms to those induced by polarized light, but in an isotropic fashion.
PAUL TRAP AND THE PROBLEM OF QUANTUM STABILITY
Authors: UGULAVA A. , CHOTORLISHVILI L. , MCHEDLISHVILI G. , NICKOLADZE K.
Published: August 2008

This work is devoted to the investigation of the possibility of controlling of ion motion inside the Paul trap. It has been shown that by proper selection of the parameters controlling the electric fields, stable localization of ions inside the Paul trap is possible. Quantum consideration of this problem is reduced to the investigation of the Mathieu–Schrodinger equation. It has been shown that quantum consideration is appreciably different from the classical one that leads to stronger limitations of the values of the parameters of stable motion. Connection between the problem under study and the possibility of experimental observation of quantum chaos has been shown.
Graft Vascular Disease: Immune Response Meets the Vessel Wall
Authors: Mitchell Richard N.
Published: August 2008

Graft vascular disease (GVD) is the single most important long-term limitation to solid-organ transplantation. It is a concentric vascular intimal hyperplastic lesion composed of smooth muscle–like cells and associated matrix. GVD diffusely involves allograft vessels, eventually compromising perfusion and resulting in graft ischemia and failure. Animal models and an increasing sophistication in analyzing human GVD have provided important new insights into GVD pathogenesis. Innate and specific immune responses both participate in the initial vascular injury; GVD develops as a consequence of downstream chemokine- and cytokine-effector pathways. Other significant developments in the field include recognition of the central pathogenic role played by interferon-γ as well as the contribution of host cell precursors to the intimal lesions. Because GVD shares many features with more common vascular pathologies, insights gleaned from our understanding of allograft vasculopathy may well impact our treatment for “traditional” atherosclerosis or restenosis lesions.
Multi - Scale Modeling and Simulation of Field-Effect Biosensors
Authors: Ringhofer Christian , Heitzinger Clemens
Published: August 2008

BioFETs (biologically sensitive field-effect transistors) are field- effect biosensors with semiconducting transducers. Their device structure is similar to a MOSFET, except that the gate structure is replaced by an aqueous solution containing the analyte. The detection mechanism is the conductance modulation of the transducer due to binding of the analyte to surface receptors. The main advantage of BioFETs, compared to currently available technology, is label-free operation. We present a quantitative analysis of BioFETs which is centered around multi-scale models. The technique for solving the multi-scale problem used here is the derivation of interface conditions for the Poisson equation that include the effects of the quasi-periodic biofunctionalized boundary layer. The multi- scale model enables self-consistent simulation and can be used with any charge transport model. Hence it provides the foundation for understanding the physics of the sensors by continuum models.
Nanocomposite of Porous Silicon and Methylene Blue Molecules for Optical Gas Sensor Application
Authors: Acosta Aldo A. , Raimundo Daniel S. , Huanca Danilo R. , Salcedo Walter J.
Published: August 2008

The present work reports the photoluminescence (PL) response of the porous silicon (PS)-methylene blue (MB) nanocomposite exposed to different organic solvents. In all the cases the PL intensity increased after gas injection. These results have been explained as a blinding effect of gas absorbed molecules, avoiding the non radiative paths. The PL responses spectra of the PL emission for different gases showed to be different patterns for each type of gases, suggesting that the PS-MB films could be applied for an optical nose system.
Secondary Ag/AgCl Pseudo-Reference Electrode on Silicon Substrate
Authors: Almeida Fernando L. , Bariatto Andrades Fontes Marcelo , Jimenez Cecilia , Burdallo Isabel
Published: August 2008

Amperometric analysis systems with two or three require a potential of reference electrode stable in function of time. In this work we developed an Ag/AgCl pseudo-reference onto gold film on silicon substrate. The amperometric electrodeposition method utilized (constant potential) provided a uniform deposited film and a controlled process characterization. It allows us to obtain electrodes with excellent performance during fourteen consecutives day. The characterization in function of the chloride concentration and time were also presented.
3D Simulation Software for Visualization of MEMS Microfabrication Processes
Authors: Colombo Fabio B. , Hokama Paula M. , Tsuda Fernando , Jankauskas Rafael G. , De Souza Douglas F. , Kayatt Pedro , Carreño Marcelo N.
Published: August 2008

In this paper we present a software for 3D visualization and simulation of the microfabrications process utilized in micro-electro-mechanical systems (MEMS) development. The simulations are based on a geometric approach and, differently from other academic and free distributed tools, the software include modules for simulation of both, bulk and surface micromachining, and for atomistic visualization of etched crystalline structures. Sophisticated rendering tools for coloring, illumination and transparency, as well as, tools to create and edit arbitrary 2D geometries and 3D solids were implemented. Related to the simulation capabilities, the bulk micromachining module lead with the anisotropic etching of (100) oriented Si substrates in alkaline solutions (KOH). The surface micromachining module works with the deposition and etching of up to 6 levels of structural and sacrificial films, which can be deposited on surfaces with complex 3D topography, and simulate the etching of sacrificial layers through etch holes in a structural layer.
DC Performance and Low Frequency Noise in n-MOSFETs using Self-Aligned Poly-Si/SiGe Gate
Authors: Jimenez Grados Hugo R. , Manera Leandro T. , Cotrin Teixeira Ricardo , Rautemberg Marcia , Diniz José A. , Doi Ioshiaki , Tatsch Peter Jurgen , Hernandes Figueroa Hugo Enrique , Swart Jacobus W.
Published: August 2008

The characterization of an n-MOS transistor with poly-Si/SiGe Gate fabricated with the CMOS process entirely developed in the Center for Semiconductor Components (CCS) at UNICAMP is presented. The Gate layer was grown by vertical LPCVD at 800 {degree sign}C. The resultant transistor has a channel region with oxide thickness of 30 nm and self-aligned thick S/D region. The DC and Gm characteristics of poly-Si/SiGe n-MOS transistor are reported. The turn-on in the I-V characteristics increases and at a drain-to-source bias VDS of +0.1 V nMOSFETs with 3 µm gate length had peak transconductance (µS) increased as well, compared with conventional n-MOS with poly-Si gate. The Gm characteristics and low frequency noise 1/f of the n-MOS transistors are studied using devices sizes with width of 20 µm and several lengths. Promising devices for RF and microwave circuit applications, show low 1/f and high values of transconductance.
Mobility Modeling in Advanced MOSFETs with Ultra-Thin Silicon Body under Stress
Authors: Sverdlov Viktor , Selberherr Siegfried
Published: August 2008

Mobility in advanced MOSFETs with strained ultra-thin silicon body is investigated. We use a two-band k·p model to describe the subband structure in strained silicon thin films. The model provides the dependence of the conductivity effective mass on strain and film thickness. The conductivity mass decreases along tensile stress in [110] direction applied to a (001) silicon film. This conductivity mass decrease ensures the mobility enhancement in MOSFETs even with extremely thin silicon films. The two-band k·p model also describes the non-parabolicity dependence on film thickness and on strain. Dependence of the non-parabolicity parameter on both film thickness and strain reduces the mobility enhancement due to the conductivity mass modification, especially at higher strain values.
Analog Performance of Dynamic Threshold Voltage SOI MOSFET.
Authors: Amaro Jefferson O. , Agopian Paula G. , Martino João A.
Published: August 2008

This work presents the study of analog performance of Dynamic Threshold Voltage SOI MOSFET (DTMOS) devices compared to the conventional SOI MOSFET. The performance of DTMOS is analyzed by two-dimensional numerical simulations. When the gate voltage increases in DTMOS (body tied to gate), there is a body potential increase, which results in a higher drain current due to the sum of the MOS current with the bipolar transistor (BJT) one. Unfortunately, in this device is not possible to apply high gate voltage. High gate voltage (above 0.7 V) causes the source junction direct bias. The drain current increase is responsible for the transconductance over drain current improvement and contributes to the increase of the device intrinsic gain up to 15 dB for devices studied. The cut-off frequency is also improved.
Flexible Power Amplifiers Designing from Device to Circuit Level by Computational Load-Pull Simulation Technique in TCAD
Authors: Kashif Ahsan U. , Azam Sher , Sevensson Christer , Wahab Qamar U.
Published: August 2008

Matching network is major issue in broadband power amplifiers due to the fact that the transistor impedances are varying both with frequency and signal level. Thus it is difficult to match these impedances both at the input and output stages. The tunable matching networks are very demanding and desired for building flexible systems, but their accuracy depends on the transistor performance under the large signal operation. Computational load pull (CLP) simulation technique is a unique way to extract the impedances of power transistor at desired frequencies which make the design of matching network much easier for multiple bands power amplifiers. An LDMOS transistor is studied and its optimum impedances are extracted at 1, 2 and 2.5 GHz. Through optimum impedance, the tunable matching networks can be easily design for broadband amplifiers.
Carriers Mobility Extraction Methods for Triple-gate FinFET
Authors: Santos Carolina D. , Martino João A.
Published: August 2008

This work presents a review of some mobility extraction methods for Triple-gate FinFET transistors. The methods are divided in two types: extraction of effective mobility, and separation of top and lateral mobility. Three-dimensional numerical simulations are performed to compare the methods. The results for effective mobility extraction show that all methods studied can be applied for Triple-gate FinFET devices with long channel length, higher than 910 nm which has an error lower than 10%. Among the method studied, the Faynot method presents lower error for shorter devices in the range from 910 nm down to 110 nm. The methods studied to extract the top and lateral mobilities show a good agreement with the expected mobility values, showing a maximum error of 11.3%, for the range of fin width of 50 nm to 9.87 µm. The Vikram method is a good option taking in consideration lower error than Daugé method and easier application than split C-V method.
A New Methodology for Characterizing the Progressive BD of Hfo2/Sio2 Metal Gate Stacks
Authors: Pagano Roberto , Lombardo Salvatore , Palumbo Felix R. , Carloni Stefania , Kirsch Paul , Krishnan Siddarth , Young Chadwin , Choi Rino , Bersuker Gennadi , Stathis James
Published: August 2008

Dielectric breakdown of nFETs with TiN metal gates and HfO2 / interfacial layer with 1.09 nm EOT is studied. Occurrence of progressive BD at low current levels is demonstrated. A new measurement methodology for extraction of the PBD time and its dependence on gate voltage are reported.
Improved Density Of States and Effective Charge Density in Si/Pecvd Sioxny Interface
Authors: Albertin Katia F. , Pereyra Inés
Published: August 2008

SiOxNy films deposited by the PECVD (Plasma Enhanced Chemical Vapor Deposition) technique at low temperatures from silane (SiH4) nitrous oxide (N2O) and helium (He) as precursor gases at different RF power and R = N2O/SiH4, in order to produce films with good SiOxNy/Si interface quality and low effective charge density were deposited and characterized. In order to compare the film structural properties with the interface (SiOxNy/Si) quality and interface charge density MOS capacitors were fabricated using these films as dielectric layer. The structure of the films was investigated by Fourier Transform Infrared Spectroscopy (FTIR). The MOS capacitors were characterized by low and high frequency capacitance (C-V) measurements, from where the interface state density, the effective charge density and the electrical breakdown were extracted. The better interface properties and a relatively low effective charge density were obtained for a film deposited with R=10 and RF power of 125 mW/cm2.
Analysis of Electromigration in Dual-Damascene Interconnect Structures
Authors: Lacerda de Orio Roberto , Carniello Sara , Ceric Hajdin , Selberherr Siegfried
Published: August 2008

We have analyzed the stress build-up and vacancy dynamics due to material transport caused by electromigration in dual-damascene interconnect structures. Our model incorporates all relevant driving forces for material transport with a complete integration of mechanical stress in connection with microstructural aspects. First, it is shown that the addition of redundant vias can be effective in increasing the interconnect lifetime, although the spacing between the vias can have a significant impact on such an approach. Then, we discuss the importance of grain boundaries in providing triple point intersections, where the combination of high vacancy concentration and high stress is likely to cause void nucleation.
Plasma Diagnostics in an Inductively Coupled Plasma - Gaseous Electronics Conference Reference Cell
Authors: Daltrini Andre M. , Moshkalev Stanislav A. , Morgan Thomas , Piejak Robert , Graham William
Published: August 2008

An Inductively Coupled Plasma - Gaseous Electronics Conference reference cell was studied by different diagnostics: laser induced fluorescence, Langmuir probe, optical emission spectroscopy (Ar line ratios) and coil electrical measurements. Two modes of operation (high and low density plasma) were analyzed. A hysteresis in the transition between modes is identified only when the applied power is considered. When the plasma power is considered (coil losses are subtracted), the plasma parameters showed a smooth behavior between the two modes. The comparison of the plasma parameters obtained by different diagnostics showed a good agreement, revealing differences in the electron energy distribution function and the usefulness of Ar line ratio method.
Post-Silicidation Annealing Effects on Electrical and Structural Properties of NiPt Germanosilicide
Authors: Eleotério Marcos A. , Doi Ioshiaki , Figueroa Robinson , Diniz José A. , Dos Santos Filho Sebastião G.
Published: August 2008

In this work NiPt germanosilicides were fabricated with 20 nm thick Ni and different Pt layer (3, 6, 9, and 12 nm thick) by rapid thermal annealing at 300 {degree sign}C, and then the post-annealing effects on these samples were investigated in the temperature range between 400 ºC to 750 ºC. The obtained silicide samples were analyzed using several characterization techniques. Smooth and uniform Ni(Pt) monogermanosilicide films have been observed for all analyzed samples. For annealing temperatures lower than 500 ºC the samples exhibited thermal stability with sheet resistances of 10 - 30 Ω/sq, and sheet resistance degradation for annealing temperatures of 500 {degree sign}C and above. Structural transformation of formed silicide to Ge rich Ni(Pt)Si1-uGeu films was found to occurs with increasing of the annealing temperature. Surface analysis revealed morphological instability of germanosilicides and strong tendency for agglomeration and mounds-like structure formation, that leads to an abrupt increase in the sheet resistance.
Electrical Characterization of Cu/Cu2O Electrodeposited Contacts
Authors: Brandt Iuri S. , Levartoski de Araujo Clodoaldo I. , Stenger Vagner , Delatorre Rafael G. , Pasa André A.
Published: August 2008

The objective of this work was to investigate the electrical properties of electrodeposited Cu/Cu2O interfaces in dark conditions. Cuprous oxide is a p-type semiconductor with application in various devices as metal base transistors, and it is very important to obtain good ohmic contacts to this electronic material. The Cu/Cu2O structures were prepared from a single bath on Si substrates by electing a specific potential for each electrodeposited layer. The electrical characterization allowed the formation of reproducible interfaces with contact resistances of 2.1 MΩ/cm2 and the determination of the resistivity of the semiconductor oxide at values of 2 x 1010 Ω.cm.
Electrical Characterization of Multi-Walled Carbon Nanotubes in 2 and 4 Terminals Configurations
Authors: Leon J , Moshkalev Stanislav A. , Flacker Alexander , Vaz Alfredo , Veríssimo Carla , De Moraes M. B.
Published: August 2008

Electrical characteristics of multi-walled carbon nanotubes (MWNTs) have been investigated as a function of the bias voltage and the nanotubes length, in 2 and 4 terminal configurations. Nanotubes were deposited over metal electrodes using ac dielectrophoresis method. For better contacts between the nanotubes and electrodes, Ni and Pd films were deposited by an electroless deposition technique. Differential conductance was found to rise considerably with bias, and this effect was more pronounced for Ni. Using two and four terminal configurations, electrical resistance measurements for individual MWNTs were performed, and the results were interpreted using the model of nanotube as a resistive transmission line, where current at low bias flows mainly through the two outermost shells.
Fabrication and Physical Characterization of Nickel Nanowires Formed by a Template-Based Electrodeposition Method
Authors: Cardoso Juliana L. , Gozzi Giuliano , Dos Santos Filho Sebastião G.
Published: August 2008

Ni nanowires were produced by electrodeposition using polycarbonate templates with different pore sizes (0.22 and 2.0 µm in diameter). Three different deposition times were used (7, 10, and 14 min.) and Atomic Force Microscopy (AFM), Field Emission Scanning Electron Microscopy (FESEM) and Rutherford Backscattering Spectrometry (RBS) were used for physical characterization of the Ni nanowires. The formation of nickel-like balls was observed after the pores were completely filled and, the results indicated the best deposition time between 10 and 14 min. Membranes with pores of 2 µm presented a better pore filling compared to 0.22 µm because of lower surface tension at the pores.
Digital Image Analysis to Determine Diameters Distribution of Nanofibers
Authors: Caliope Priscila B. , Del-Moral-Hernandez Emilio , Silva Ana N.
Published: August 2008

The electrospinning technique may be considered a simple and convenient process to provide polymers and ceramic fibers with both solid and hollow interiors that are exceptionally long in length, uniform in diameter, varying within the interval of few nanometers to several microns, and diversified in composition. Despite the scanning electron microscopy (SEM) versatility and potencially, there is a serious problem in characterizing nanofibers, as this is not made automatically. This work discusses the problems regarding a method for automatic measurement in SEM images proposed in (2). The images colleted from the microscope were analyzed by imagery processing techniques for determining the diameters of the nanofibers; the main drawbacks of the method proposed will be argued and some solutions will be offered.
A Possible Optodevice using a Single Molecule of Dithiothreitol
Authors: Lohmann Daniel , Da Cunha Carlo R.
Published: August 2008

In this work we study the electronic properties of a single molecule of dithiothreitol. The non-equilibrium Green's functions formalism was used for theoretically calculating its electrical properties. The results of the simulation indicate a HOMO-LUMO separation of approximately 10 eV, which masks any peaking of the conductance and current. We propose a model based on the tunneling current as the major transport mechanism through this molecule and speculate its potential for optical applications.
The Device-Technological Simulation of The Field-Emission Micro-Cathodes Based on Three-Dimensional Soi-Structures
Authors: Druzhynin Anatolij , Holota Victor , Kohut Igor , Sapon Sergij , Khoverko Yurij
Published: August 2008

The two methods of the formation of the silicon-on-insulator (SOI) local structures have been proposed. The first one is based on the stimulated lateral epitaxial growth and planarization of Si mono-crystal film. The second one is based on local thermal oxidation of Si buried layer through horizontal tunnels. The obtained SOI-structures are used in a base matrix crystal fabrication technology for the construction of micro-systems. It is proposed to add to elements of a base crystal of a matrix of cells of field emission micro-cathodes with control circuits. The fabrication technology and the layout of a field emission micro-cathode cell with control high-voltage SOI MOS-transistor has been developed. The computer simulation of high-voltage SOI MOS-transistor static characteristics has been performed.
Electrical Transport Mechanisms in Mono-Layer Phthalocyanine Device
Authors: Raimundo Daniel S. , Stelet Adriana B. , Huanca Danilo R. , Salcedo Walter J.
Published: August 2008

The present work reports the electrical transport mechanism in the phthalocyanine monolayer onto the porous silicon structure. A device was fabricated with gold electrodes based on the phthalocyanine molecules film deposited onto oxidized porous silicon. From the I-V curves, the carrier transport mechanism through the phthalocianine film and the junction type in the phthalocyanine-electrode region were identified. The mechanism is based on the current limited by the trapped charges in the highly localized levels inside the band gap between the HOMO and LUMO levels of the phtalocyanine molecules. The I-V response of the device showed that the device is sensitive to organic gases exposition, showing higher sensibility to methanol moiety.
Characterization of Plastic Packaging with Fringing Electric Field Sensors
Authors: Sundara-Rajan Kishore , Mathur Abhinav , Mamishev Alexander
Published: August 2008

Stability of plastic packaging for electronic circuits and electrical devices partially depends on moisture penetration into the bulk of the package, especially for applications in harsh environments. Therefore, a technique capable of moisture diffusion dynamics in plastics would be valuable for design, testing, and field deployment of electronic devices. This paper presents a proof of concept experiment that demonstrates the viability of using electrical impedance spectroscopy and non-stationary fringing electric field sensors to obtain a one-dimensional profile of moisture distribution in plastics and composite materials. A fixed penetration depth sensor is moved orthogonal to the surface of the sample, and the resulting profile is a spatial convolution of progressive addition of different layers of the sample. Qualitative explanation of the experimental results is given and a roadmap for future work is laid out.
Inhibiting intestinal NPC1L1 activity prevents diet-induced increase in biliary cholesterol in Golden Syrian hamsters
Authors: Valasek Mark A. , Repa Joyce J. , Quan Gang , Dietschy John M. , Turley Stephen D.
Published: August 2008

Niemann-Pick C1-like 1 (NPC1L1) facilitates the uptake of sterols into the enterocyte and is the target of the novel cholesterol absorption inhibitor, ezetimibe. These studies used the Golden Syrian hamster as a model to delineate the changes in the relative mRNA expression of NPC1L1 and other proteins that regulate sterol homeostasis in the enterocyte during and following cessation of ezetimibe treatment and also to address the clinically important question of whether the marked inhibition of cholesterol absorption alters biliary lipid composition. In hamsters fed a low-cholesterol, low-fat basal diet, the abundance of mRNA for NPC1L1 in the small intestine far exceeded that in other regions of the gastrointestinal tract, liver, and gallbladder. In the first study, female hamsters were fed the basal diet containing ezetimibe at doses up to 2.0 mg·day−1·kg body wt−1. At this dose, cholesterol absorption fell by 82%, fecal neutral sterol excretion increased by 5.3-fold, and hepatic and intestinal cholesterol synthesis increased more than twofold, but there were no significant changes in either fecal bile acid excretion or biliary lipid composition. The ezetimibe-induced changes in intestinal cholesterol handling were reversed when treatment was withdrawn. In a second study, male hamsters were given a diet enriched in cholesterol and safflower oil without or with ezetimibe. The lipid-rich diet raised the absolute and relative cholesterol levels in bile more than fourfold. This increase was largely prevented by ezetimibe. These data are consistent with the recent finding that ezetimibe treatment significantly reduced biliary cholesterol saturation in patients with gallstones.
Lipopolysaccharide activates NF-κB by TLR4-Bcl10-dependent and independent pathways in colonic epithelial cells
Authors: Bhattacharyya Sumit , Dudeja Pradeep K. , Tobacman Joanne K.
Published: August 2008

In colonic epithelium, one of the pathways of lipopolysaccharide (LPS) activation of NF-κB and IL-8 is via Toll-like receptor (TLR)4, MyD88, IRAK1/4, and B-cell CLL/lymphoma 10 (Bcl10). However, this innate immune pathway accounts for only ∼50% of the NF-κB activation, so additional mechanisms to explain the LPS-induced effects are required. In this report, we identify a second pathway of LPS-induced stimulation, mediated by reactive oxygen species (ROS), in human colonic epithelial tissue cells in tissue culture and in ex vivo mouse colonic tissue. Measurements of IL-8, KC, Bcl10, phospho-IκBα, nuclear NF-κB, and phosphorylated Hsp27 were performed by ELISA. The TLR4-Bcl10 pathway was inhibited by Bcl10 siRNA and in studies with colonic tissue from the TLR4-deficient mouse. The ROS pathway was inhibited by Tempol, a free radical scavenger, or by okadaic acid, an inhibitor of Hsp27 dephosphorylation by protein phosphatase 2A (PP2A). The ROS pathway was unaffected in the TLR4-deficient tissue or by silencing of Bcl10. The combination of exposure to the free radical scavenger Tempol and of TLR4 or Bcl10 suppression was required to completely inhibit the LPS-induced activation. The ROS pathway was associated with dephosphorylation of Hsp27. LPS appears to activate both the regulatory component of the IκBα-kinase (IKK) signalosome through Bcl10 interaction with Nemo (IKKγ) and the catalytic component through Hsp27 interaction with IKKβ. Since LPS exposure is associated with septic shock and the systemic inflammatory response syndrome, distinguishing between these two pathways of LPS activation may facilitate new approaches to prevention and treatment.
Age-related changes in the biomechanics of left ventricular twist measured by speckle tracking echocardiography
Authors: van Dalen Bas M. , Soliman Osama I. I. , Vletter Wim B. , ten Cate Folkert J. , Geleijnse Marcel L.
Published: August 2008

The increasing number and proportion of aged individuals in the population warrants knowledge of normal physiological changes of left ventricular (LV) biomechanics with advancing age. LV twist describes the instantaneous circumferential motion of the apex with respect to the base of the heart and has an important role in LV ejection and filling. This study sought to investigate the biomechanics behind age-related changes in LV twist by determining a broad spectrum of LV rotation parameters in different age groups, using speckle tracking echocardiography (STE). The final study population consisted of 61 healthy volunteers (16–35 yr, n = 25; 36–55 yr, n = 23; 56–75 yr, n = 13; 31 men). LV peak systolic rotation during the isovolumic contraction phase (Rotearly), LV peak systolic rotation during ejection (Rotmax), instantaneous LV peak systolic twist (Twistmax), the time to Rotearly, Rotmax, and Twistmax, and rotational deformation delay (defined as the difference of time to basal Rotmax and apical Rotmax) were determined by STE using QLAB Advanced Quantification Software (version 6.0; Philips, Best, The Netherlands). With increasing age, apical Rotmax ( P < 0.05), time to apical Rotmax ( P < 0.01), and Twistmax ( P < 0.01) increased, whereas basal Rotearly ( P < 0.001), time to basal Rotearly ( P < 0.01), and rotational deformation delay ( P < 0.05) decreased. Rotational deformation delay was significantly correlated to Twistmax ( R2 = 0.20, P < 0.05). In conclusion, Twistmax increased with aging, resulting from both increased apical Rotmax and decreased rotational deformation delay between the apex and the base of the LV. This may explain the preservation of LV ejection fraction in the elderly.
Temporally controlled overexpression of cardiac-specific PI3Kα induces enhanced myocardial contractility—a new transgenic model
Authors: Yano Naohiro , Tseng Andy , Zhao Ting C. , Robbins Jeffrey , Padbury James F. , Tseng Yi-Tang
Published: August 2008

The phosphatidylinositol 3-kinase (PI3K) signaling pathway regulates multiple cellular processes including cell survival/apoptosis and growth. In the cardiac context, PI3Kα plays important roles in cardiac growth. We have shown that cardiac PI3K activity is highly regulated during development, with the highest levels found during the fetal-neonatal transition period and the lowest levels in the adult. There is a close relationship between cardiomyocyte proliferation and cardiac PI3K activity. In adult transgenic mice, however, the prolonged constitutive activation of PI3Kα in the heart results in hypertrophy. To develop a strategy to allow temporally controlled overexpression of cardiac PI3Kα, we engineered a tetracycline (tet) transactivator tet-off controlled transgenic mouse line with a conditional overexpression of a cardiac-specific fusion protein of the SH2 domain of p85 and p110α. Cardiac PI3K activity and Akt phosphorylation were significantly increased in adult mice after transgene induction following the removal of doxycycline for 2 wk. The heart weight-to-body weight ratio was not changed, and there were no signs of cardiomyopathy. The overexpression of PI3Kα resulted in increased left ventricular (LV) developed pressure and the maximal and minimal positive values of the first derivative of LV pressure, but not heart rate, as assessed in Langendorff hearts. Mice overexpressing PI3Kα also had increases in the levels of Ca2+-regulating proteins, including the L-type Ca2+ channels, ryanodine receptors, and sarco(endo)plasmic reticulum Ca2+-ATPase 2a. Thus the temporally controlled overexpression of cardiac PI3Kα does not induce hypertrophy or cardiomyopathy but results in increased contractility, probably via the increased expression of multiple Ca2+-regulating proteins. These distinct phenotypes suggest a fundamental difference between transgenic mice with temporal or prolonged activation of cardiac PI3Kα.
Role played by acid-sensitive ion channels in evoking the exercise pressor reflex
Authors: Hayes Shawn G. , McCord Jennifer L. , Rainier Jon , Liu Zhuqing , Kaufman Marc P.
Published: August 2008

The exercise pressor reflex arises from contracting skeletal muscle and is believed to play a role in evoking the cardiovascular responses to static exercise, effects that include increases in arterial pressure and heart rate. This reflex is believed to be evoked by the metabolic and mechanical stimulation of thin fiber muscle afferents. Lactic acid is known to be an important metabolic stimulus evoking the reflex. Until recently, the only antagonist for acid-sensitive ion channels (ASICs), the receptors to lactic acid, was amiloride, a substance that is also a potent antagonist for both epithelial sodium channels as well as voltage-gated sodium channels. Recently, a second compound, A-317567, has been shown to be an effective and selective antagonist to ASICs in vitro. Consequently, we measured the pressor responses to the static contraction of the triceps surae muscles in decerebrate cats before and after a popliteal arterial injection of A-317567 (10 mM solution; 0.5 ml). We found that this ASIC antagonist significantly attenuated by half ( P < 0.05) the pressor responses to both contraction and to lactic acid injection into the popliteal artery. In contrast, A-317567 had no effect on the pressor responses to tendon stretch, a pure mechanical stimulus, and to a popliteal arterial injection of capsaicin, which stimulated transient receptor potential vanilloid type 1 channels. We conclude that ASICs on thin fiber muscle afferents play a substantial role in evoking the metabolic component of the exercise pressor reflex.
3D 3He diffusion MRI as a local in vivo morphometric tool to evaluate emphysematous rat lungs
Authors: Jacob R. E. , Minard K. R. , Laicher G. , Timchalk C.
Published: August 2008

In this work, we investigate 3He magnetic resonance imaging as a noninvasive morphometric tool to assess emphysematous disease state on a local level. Emphysema was induced intratracheally in rats with 25 U/100 g body wt of porcine pancreatic elastase dissolved in 200 μl saline. Rats were then paired with saline-dosed controls. Nine three-dimensional (3D) 3He diffusion-weighted images were acquired at 1, 2, or 3 wk postdose, after which the lungs were harvested and prepared for histological analysis. Recently introduced indexes sensitive to the heterogeneity of the air space size distribution were calculated. These indexes, D1 and D2, were derived from the moments of the mean equivalent airway diameters. Averaged over the entire lung, it is shown that the average 3He diffusivity ( Dave) correlates well with histology ( R = 0.85, P < 0.0001). By matching small (0.046 cm2) regions in 3He images with corresponding regions in histological slices, Dave correlates significantly with both D 1 and D 2 ( R = 0.88 and R = 0.90, respectively, with P < 0.0001). It is concluded that 3He MRI is a viable noninvasive morphometric tool for localized in vivo emphysema assessment.
Aging affects vascular structure and function in a limb-specific manner
Authors: Nishiyama Steven K. , Wray D. Walter , Richardson Russell S.
Published: August 2008

The limb-specific effects of aging upon vessel structure and function are not well understood. Consequently, in 12 young (26 ± 2 yr) and 12 old (72 ± 1 yr) healthy subjects, we utilized ultrasound Doppler to evaluate intima-media thickness (IMT), ischemic reperfusion, and flow-mediated dilation (FMD) following (5 min) suprasystolic cuff occlusion in both the arm [brachial artery (BA)] and the leg [popliteal artery (PA)]. Structural measurements, whether normalized for vessel size or not, revealed a greater IMT in both the BA and PA with age (young: BA 0.028 ± 0.001 and PA 0.046 ± 0.003 cm, old: BA 0.039 ± 0.002 and PA 0.073 ± 0.005 cm; P < 0.05). Ischemic reperfusion revealed a similar pattern as IMT in terms of limb and age-related differences. There was an age-related attenuation in both BA FMD (old: 38% smaller BA FMD compared with young) and PA FMD (old: 71% smaller PA FMD compared with young). However, when this percent change was normalized for shear rate, only the PA FMD of the old group was still significantly attenuated (old: 41% smaller PA FMD/shear rate compared with young). Together, the finding of differential structural and functional parameters in the arms and legs of healthy young people, and the somewhat negative findings that are specific to the legs of otherwise healthy older people (greater IMT and attenuated FMD), support and may help to better understand the increased propensity to develop a vascular pathology in the legs with age.
Arginase and vascular aging
Authors: Santhanam Lakshmi , Christianson David W. , Nyhan Daniel , Berkowitz Dan E.
Published: August 2008

Vascular and associated ventricular stiffness is one of the hallmarks of the aging cardiovascular system. Both an increase in reactive oxygen species production and a decrease in nitric oxide (NO) bioavailability contribute to the endothelial dysfunction that underlies this vascular stiffness, independent of other age-related vascular pathologies such as atherosclerosis. The activation/upregulation of arginase appears to be an important contributor to age-related endothelial dysfunction by a mechanism that involves substrate (l-arginine) limitation for NO synthase (NOS) 3 and therefore NO synthesis. Not only does this lead to impaired NO production but also it contributes to the enhanced production of reactive oxygen species by NOS. Although arginase abundance is increased in vascular aging models, it appears that posttranslational modification by S-nitrosylation of the enzyme enhances its activity as well. The S-nitrosylation is mediated by the induction of NOS2 in the endothelium. Furthermore, arginase activation contributes to aging-related vascular changes by mechanisms that are not directly related to changes in NO signaling, including polyamine-dependent vascular smooth muscle proliferation and collagen synthesis. Taken together, arginase may represent an as yet elusive target for the modification of age-related vascular and ventricular stiffness contributing to cardiovascular morbidity and mortality.
Respiratory-related evoked potential measures of respiratory sensory gating
Authors: Chan Pei-Ying Sarah , Davenport Paul W.
Published: August 2008

The purpose of this study was to demonstrate a neural respiratory gating system using a paired stimuli paradigm. The N1 peak of the respiratory-related evoked potential (RREP) represents early perceptual processing of respiratory sensory information. This is similar to the N100 peak shown with tactile sensation, where the second peak amplitude (S2) of the N100 peak from the somatosensory evoked potential (SEP) was smaller than the first peak amplitude (S1) when the stimuli were presented 500 ms apart. We hypothesized that paired inspiratory occlusions would result in a reduced amplitude of the S2 N1 RREP peak amplitude, indicating respiratory central neural gating. Twenty healthy subjects (10 men and 10 women; 25.8 ± 6.5 yr old) completed the paired inspiratory occlusion (RREP) trial. Thirteen of the subjects also completed the paired mouth air puffs [mouth-evoked potential (MEP) trial], and the paired hand air puffs (SEP) trial. All paired presentations were separated by 500 ms. The N1 peak amplitudes of the RREP trial and the N100 peak amplitudes of the MEP and SEP trials for S1 and S2 and the S2/S1 ratios were determined. The S1 RREP N1 peak amplitude was significantly greater than S2, and the S2/S1 ratio was 0.43. The S1 MEP and SEP N100 peak amplitudes were significantly greater than S2, and the N100 ratio was 0.49 and 0.49, respectively. These results are consistent with central neural gating of respiratory afferent input. The RREP gating response is similar to somatosensory mechanoreceptor gating.
Effect of the ATP-binding cassette drug transporters ABCB1, ABCG2, and ABCC2 on erlotinib hydrochloride (Tarceva) disposition inin vitroandin vivopharmacokinetic studies employing Bcrp1−/−/Mdr1a/1b−/− (triple-knockout) and wild-type mice
Authors: Marchetti Serena , de Vries Nienke A. , Buckle Tessa , Bolijn Maria J. , van Eijndhoven Maria A.J. , Beijnen Jos H. , Mazzanti Roberto , van Tellingen Olaf , Schellens Jan H.M.
Published: August 2008

We tested whether erlotinib hydrochloride (Tarceva, OSI-774), an orally active epidermal growth factor receptor tyrosine kinase inhibitor, is a substrate for the ATP-binding cassette drug transporters P-glycoprotein (P-gp; MDR1, ABCB1), breast cancer resistance protein (BCRP; ABCG2), and multidrug resistance protein 2 (MRP2; ABCC2) in vitro and whether P-gp and BCRP affect the oral pharmacokinetics of erlotinib hydrochloride in vivo. In vitro cell survival, drug transport, accumulation, and efflux of erlotinib were done using Madin-Darby canine kidney II [MDCKII; wild-type (WT), MDR1, Bcrp1, and MRP2] and LLCPK (WT and MDR1) cells and monolayers as well as the IGROV1 and the derived human BCRP-overexpressing T8 cell lines. In vivo, the pharmacokinetics of erlotinib after p.o. and i.p. administration was studied in Bcrp1/Mdr1a/1b−/− (triple-knockout) and WT mice. In vitro, erlotinib was actively transported by P-gp and BCRP/Bcrp1. No active transport of erlotinib by MRP2 was observed. In vivo, systemic exposure (P = 0.01) as well as bioavailability of erlotinib after oral administration (5 mg/kg) were statistically significantly increased in Bcrp1/Mdr1a/1b−/− knockout mice (60.4%) compared with WT mice (40.0%; P = 0.02). Conclusion: Erlotinib is transported efficiently by P-gp and BCRP/Bcrp1 in vitro. In vivo, absence of P-gp and Bcrp1 significantly affected the oral bioavailability of erlotinib. Possible clinical consequences for drug-drug and drug-herb interactions in patients in the gut between P-gp/BCRP-inhibiting substrates and oral erlotinib need to be addressed. [Mol Cancer Ther 2008;7(8):2280–7]
Tumor necrosis factor-α–induced accentuation in cryoinjury: mechanisms in vitro and in vivo
Authors: Jiang Jing , Goel Raghav , Iftekhar M. Arif , Visaria Rachana , Belcher John D. , Vercellotti Gregory M. , Bischof John C.
Published: August 2008

Cryosurgical treatment of solid cancer can be greatly assisted by further translation of our finding that a cytokine adjuvant tumor necrosis factor-α (TNF-α) can achieve complete cancer destruction out to the intraoperatively imaged iceball edge (-0.5°C) over the current clinical recommendation of reaching temperatures lower than -40°C. The present study investigates the cellular and tissue level dose dependency and molecular mechanisms of TNF-α-induced enhancement in cryosurgical cancer destruction. Microvascular endothelial MVEC and human prostate cancer LNCaP Pro 5 (LNCaP) cells were frozen as monolayers in the presence of TNF-α. Normal skin and LNCaP tumor grown in a nude mouse model were also frozen at different TNF-α doses. Molecular mechanisms were investigated by using specific inhibitors to block nuclear factor-κB–mediated inflammatory or caspase-mediated apoptosis pathways. The amount of cryoinjury increased in a dose-dependent manner with TNF-α both in vitro and in vivo. MVEC were found to be more cryosensitive than LNCaP cells in both the presence and the absence of TNF-α. The augmentation in vivo was significantly greater than that in vitro, with complete cell death up to the iceball edge in tumor tissue at local TNF-α doses greater than 200 ng. The inhibition assays showed contrasting results with caspase-mediated apoptosis as the dominant mechanism in MVEC in vitro and nuclear factor-κB–mediated inflammatory mechanisms within the microvasculatures the dominant mechanism in vivo. These results suggest the involvement of endothelial-mediated injury and inflammation as the critical mechanisms in cryoinjury and the use of vascular-targeting molecules such as TNF-α to enhance tumor killing and achieve the clinical goal of complete cell death within an iceball. [Mol Cancer Ther 2008;7(7):2547–55]