bluuebunny/crossref_metadata_2025 huggingface dataset:
The anchoring protein SAP97 retains Kv1.5 channels in the plasma membrane of cardiac myocytes
Authors: Abi-Char Joëlle , El-Haou Saïd , Balse Elise , Neyroud Nathalie , Vranckx Roger , Coulombe Alain , Hatem Stéphane N.
Published: February 2008

Membrane- associated guanylate kinase proteins (MAGUKs) are important determinants of localization and organization of ion channels into specific plasma membrane domains. However, their exact role in channel function and cardiac excitability is not known. We examined the effect of synapse-associated protein 97 (SAP97), a MAGUK abundantly expressed in the heart, on the function and localization of Kv1.5 subunits in cardiac myocytes. Recombinant SAP97 or Kv1.5 subunits tagged with green fluorescent protein (GFP) were overexpressed in rat neonatal cardiac myocytes and in Chinese hamster ovary (CHO) cells from adenoviral or plasmidic vectors. Immunocytochemistry, fluorescence recovery after photobleaching, and patch-clamp techniques were used to study the effects of SAP97 on the localization, mobility, and function of Kv1.5 subunits. Adenovirus-mediated SAP97 overexpression in cardiac myocytes resulted in the clustering of endogenous Kv1.5 subunits at myocyte-myocyte contacts and an increase in both the maintained component of the outward K+current, IKur(5.64 ± 0.57 pA/pF in SAP97 myocytes vs. 3.23 ± 0.43 pA/pF in controls) and the number of 4-aminopyridine-sensitive potassium channels in cell-attached membrane patches. In live myocytes, GFP-Kv1.5 subunits were mobile and organized in clusters at the basal plasma membrane, whereas SAP97 overexpression reduced their mobility. In CHO cells, Kv1.5 channels were diffusely distributed throughout the cell body and freely mobile. When coexpressed with SAP97, Kv subunits were organized in plaquelike clusters and poorly mobile. In conclusion, SAP97 regulates the K+current in cardiac myocytes by retaining and immobilizing Kv1.5 subunits in the plasma membrane. This new regulatory mechanism may contribute to the targeting of Kv channels in cardiac myocytes.
Heat shock protein 90 inhibitors attenuate LPS-induced endothelial hyperpermeability
Authors: Chatterjee Anuran , Snead Connie , Yetik-Anacak Gunay , Antonova Galina , Zeng Jingmin , Catravas John D.
Published: February 2008

Endothelial hyperperme ability leading to vascular leak is an important consequence of sepsis and sepsis-induced lung injury. We previously reported that heat shock protein (hsp) 90 inhibitor pretreatment improved pulmonary barrier dysfunction in a murine model of sepsis-induced lung injury. We now examine the effects of hsp90 inhibitors on LPS-mediated endothelial hyperpermeability, as reflected in changes in transendothelial electrical resistance (TER) of bovine pulmonary arterial endothelial cells (BPAEC). Vehicle-pretreated cells exposed to endotoxin exhibited a concentration-dependent decrease in TER, activation of pp60Src, phosphorylation of the focal adhesion protein paxillin, and reduced expression of the adherens junction proteins, vascular endothelial (VE)-cadherin and β-catenin. Pretreatment with the hsp90 inhibitor, radicicol, prevented the decrease in TER, maintained VE-cadherin and β-catenin expression, and inhibited activation of pp60Srcand phosphorylation of paxillin. Similarly, when BPAEC hyperpermeability was induced by endotoxin-activated neutrophils, pretreatment of neutrophils and/or endothelial cells with radicicol protected against the activated neutrophil-induced decrease in TER. Increased paxillin phosphorylation and decreased expression of β-catenin and VE-cadherin were also observed in mouse lungs 12 h after intraperitoneal endotoxin and attenuated in mice pretreated with radicicol. These results suggest that hsp90 plays an important role in sepsis-associated endothelial barrier dysfunction.
Small Reservoir Impact on Simulated Watershed-Scale Nutrient Yield
Authors: Prochnow Shane J. , White Joseph D. , Scott Thad , Filstrup Christopher
Published: February 2008

The soil and water assessment tool (SWAT) is used to assess the influence of small upland reservoirs (PL566) on watershed nutrient yield. SWAT simulates the impact of collectively increasing and decreasing PL566 magnitudes (size parameters) on the watershed. Totally removing PL566 reservoirs results in a 100%increase in total phosphorus and an 82%increase in total nitrogen, while a total maximum daily load (TMDL) calling for a 50%reduction in total phosphorus can be achieved with a 500%increase in the magnitude of PL566s in the watershed. PL566 reservoirs capture agriculture pollution in surface flow, providing long-term storage of these constituents when they settle to the reservoir beds. A potential strategy to reduce future downstream nutrient loading is to enhance or construct new PL566 reservoirs in the upper basin to better capture agricultural runoff.
On Polynomials of the Formxrf(x(q−1)/l)
Authors: Akbary Amir , Wang Qiang
Published: February 2008

We give a general criterion for permutation polynomials of the formxrf(x(q−1)/l), wherer≥1,l≥1andl∣(q−1). We employ this criterion to characterize several classes of permutation polynomials.
Characterization and Application of the Thermal Neutron Radiography Beam in the Egyptian Second Experimental and Training Research Reactor (ETRR-2)
Authors: Abou Mandour M. A. , Megahid R. M. , Hassan M. H. , Abd El Salam T. M.
Published: February 2008

The Experimental, Training, Research Reactor (ETRR-2) is an open-pool multipurpose reactor (MPR) with a core power of 22 MWthcooled and moderated by light water and reflected with beryllium. It has four neutron beams and a thermal column as the main experimental devices. The neutron radiography facility unit utilizes one of the radial beam tubes. The track-etch technique using nitrocellulose films and converter screen is applied. In this work, the radial neutron beam for the thermal neutron radiography facility has been characterized and the following values were determined: thermal flux of1.5×107 n/cm2⋅s,nth/γratio of0.1×106 n⋅cm−2⋅mR−1; a Cd ratio of 10.26, a resolution of 0.188 mm, and L/D ratio of 117.3. This characterization verifies the design parameters of the unit. Various radiographs were taken and results indicate that the neutron radiography facility of the ETRR-2 holds promising opportunities for nuclear as well as nonnuclear applications.
Bioengineering of Improved Biomaterials Coatings for Extracorporeal Circulation Requires Extended Observation of Blood-Biomaterial Interaction under Flow
Authors: Stevens Kris N. J. , Aldenhoff Yvette B. J. , van der Veen Frederik H. , Maessen Jos G. , Koole Leo H.
Published: February 2008

Extended use of cardiopulmonary bypass (CPB) systems is often hampered by thrombus formation and infection. Part of these problems relates to imperfect hemocompatibility of the CPB circuitry. The engineering of biomaterial surfaces with genuine long-term hemocompatibility is essentially virgin territory in biomaterials science. For example, most experiments with the well-known Chandler loop model, for evaluation of blood-biomaterial interactions under flow, have been described for a maximum duration of 2 hours only. This study reports a systematic evaluation of two commercial CPB tubings, each with a hemocompatible coating, and one uncoated control. The experiments comprised (i) testing over 5 hours under flow, with human whole blood from 4 different donors; (ii) measurement of essential blood parameters of hemocompatibility; (iii) analysis of the luminal surfaces by scanning electron microscopy and thrombin generation time measurements. The dataset indicated differences in hemocompatibility of the tubings. Furthermore, it appeared that discrimination between biomaterial coatings can be made only after several hours of blood-biomaterial contact. Platelet counting, myeloperoxidase quantification, and scanning electron microscopy proved to be the most useful methods. These findings are believed to be relevant with respect to the bioengineering of extracorporeal devices that should function in contact with blood for extended time.
Network Provisioning Using Multimedia Aggregates
Authors: Hernández-Orallo Enrique , Vila-Carbó Joan
Published: February 2008

Multimedia traffic makes network provisioning a key issue. Optimal provisioning of network resources is crucial for reducing the service cost of multimedia transmission. Multimedia traffic requires not only provisioning bandwidth and buffer resources in the network but also guaranteeing a given maximum end-to-end delay. In this paper we present methods and tools for the optimal dimensioning of networks based on multimedia aggregates. The proposed method minimises the network resources reservations of traffic aggregates providing a bounded delay. The paper also introduces several methods to generate multimedia traffic aggregation using real video traces. The method is evaluated using a network topology based on the European GÉANT network. The results of these simulations allow us to discover the relationship between a required delay and the necessary bandwidth reservation (or the achievable utilisation limit). An interesting conclusion of these scenarios is that, following several recommendations, the network utilisation can reach values of around80%or higher.
Freeform Fabrication of Titanium Aluminide via Electron Beam Melting Using Prealloyed and Blended Powders
Authors: Cormier Denis , Harrysson Ola , Mahale Tushar , West Harvey
Published: February 2008

Titanium aluminide (TiAl) is an intermetallic compound possessing excellent high-temperature performance while having significantly lower density than nickel-based superalloys. This paper presents preliminary results of experiments aimed at processing TiAl via the electron beam melting (EBM) process. Two processing routes are explored. The first uses prealloyed powder, whereas the second explores controlled reaction synthesis. Issues such as processing parameters, vaporization of alloying elements, microstructure, and properties are discussed.
Is Climate Change a Possible Explanation for Woody Thickening in Arid and Semi-Arid Regions?
Authors: Eamus Derek , Palmer Anthony R.
Published: February 2008

Increased woody plant density (woody encroachment or woody thickening) is a globally observed phenomenon. Similarly, increased atmospheric carbon dioxide concentrations and decreased pan evaporation rates are globally observed phenomena. In this paper, we propose that the former (increased woody plant density) is a product of the latter. We propose that decreased stomatal conductance and increased rates of carbon fixation arising from an enriched atmospheric carbon dioxide concentration, in conjunction with reduced rates of pan evaporation, result in increased woody plant density. We suggest that this is analogous to the increased woody plant density that is observed along rainfall gradients that span arid to mesic environments. From this conceptual model, we make three predictions, namely, that (a) long-term trends in tree water-use-efficiency should reveal increased values; (b) run-off data should show an increase where woody thickening is occurring; (c) enrichedCO2experiments should reveal an enhanced plant water status. These three predictions are discussed and shown to be supported by experimental data.
Stability Analysis ofθ-Methods for Neutral Multidelay Integrodifferential System
Authors: Xu Y. , Zhao J. J. , Sui Z. N.
Published: February 2008

This paper studies the stability of a class of neutral delay integrodifferential system. A necessary and sufficient condition of stability for its analytic solutions is considered. The improvedθ-methods are developed. Some numerical stability properties are obtained and numerical experiments are given.
On Zeros of Self-Reciprocal Random Algebraic Polynomials
Authors: Farahmand K.
Published: February 2008

This paper provides an asymptotic estimate for the expected number
of level crossings of a trigonometric polynomial TN(θ)=∑j=0N−1{αN−jcos(j+1/2)θ+βN−jsin(j+1/2)θ}, where αj and βj, j=0,1,2,…, N−1, are sequences of independent identically distributed normal standard random variables. This type of random polynomial is produced in the study of random
algebraic polynomials with complex variables and complex random coefficients,
with a self-reciprocal property. We establish the relation between this type of random algebraic polynomials and the above random trigonometric polynomials, and we show that the required level crossings have the functionality form of cos(N+θ/2). We also discuss the relationship which exists and can be explored further between our random polynomials and random matrix theory.
A2×1LINC Transceiver for Enhanced Power Transmission in Wireless Systems
Authors: Abd Elaal Mohamed , Ghannouchi Fadhel
Published: February 2008

A2×1LINC transceiver based on linear amplification using nonlinear components (LINC) architecture for wireless systems applications is proposed. The layout of the new architecture is presented and the simulation results show that the overall power efficiency of this architecture is superior by more than 300% when compared with that of a regular LINC amplifier. Also the adjacent channel power ratio (ACPR) is lowered to−64.2dBc, compared to−26.1dBc for regular LINC, which improves the system immunity against complex gain imbalances between LINC branches.
Relap5 Analysis of Processes in Reactor Cooling Circuit and Reactor Cavity in Case of Station Blackout in RBMK-1500
Authors: Kaliatka Algirdas , Uspuras Eugenijus , Rimkevicius Sigitas
Published: February 2008

Ignalina NPP is equipped with channel-type boiling-water graphite-moderated reactor RBMK-1500. Results of the level-1 probabilistic safety assessment of the Ignalina NPP have shown that in topography of the risk, the transients with failure of long-term core cooling other than LOCA are the main contributors to the core damage frequency. The total loss of off-site power with a failure to start any diesel generator, that is station blackout, is the event which could lead to the loss of long-term core cooling. Such accident could lead to multiple ruptures of fuel channels with severe consequences and should be analyzed in order to estimate the timing of the key events and the possibilities for accident management. This paper presents the results of the analysis of station blackout at Ignalina NPP. Analysis was performed using thermal-hydraulic state-of-the-art RELAP5/MOD3.2 code. The response of reactor cooling system and the processes in the reactor cavity and its venting system in case of a few fuel-channel ruptures due to overheating were demonstrated. The possible measures for prevention of the development of this beyond design basis accident (BDBA) to a severe accident are discussed.
Classifying EEG for Brain-Computer Interface: Learning Optimal Filters for Dynamical System Features
Authors: Song Le , Epps Julien
Published: February 2008

Classification of multichannel EEG recordings during motor imagination has been exploited successfully for brain-computer interfaces (BCI). In this paper, we consider EEG signals as the outputs of a networked dynamical system (the cortex), and exploit synchronization features from the dynamical system for classification. Herein, we also propose a new framework for learning optimal filters automatically from the data, by employing a Fisher ratio criterion. Experimental evaluations comparing the proposed dynamical system features with the CSP and the AR features reveal their competitive performance during classification. Results also show the benefits of employing the spatial and the temporal filters optimized using the proposed learning approach.
Ecology and Conservation of the Critically Endangered Tree SpeciesGymnocladus assamicusin Arunachal Pradesh, India
Authors: Choudhury B. I. , Khan M. L. , Arunachalam A. , Das A. K.
Published: February 2008

Gymnocladus assamicusis a critically endangered leguminous tree species endemic to Northeast India. Mature pods of the trees yield soap material and are collected by local people for domestic purposes and religious activities.G. assamicusgrows on hill slopes and along banks of streams. Male and hermaphrodite flowers are borne by separate individual trees. Altogether 28 mature trees were documented from nine populations. Of these, very few regenerating trees were found. This species regenerates only through seeds. The major constraints to natural regeneration are overharvesting of mature fruits, habitat destruction, grazing, predation of seeds by scatter-hoarding animals, poor percentage of seed germination due to their hard-waxy seed coats, and the lack of seed dispersal. Effective conservation initiatives should emphasize sustainable harvesting of mature pods, awareness among local people, and preservation of surviving individuals of the species. Nonetheless, reintroduction of the species to suitable ecological habitats is also recommended.
Stochastic Processes with a Particular Type of Variograms
Authors: Ma Chunsheng
Published: February 2008

This paper is concerned with a class of stochastic processes or random fields with second-order increments, whose variograms have a particular form, among which stochastic processes having orthogonal increments on the real line form an important subclass. A natural issue, how big this subclass is, has not been explicitly addressed in the literature. As a solution, this paper characterizes a stochastic process having orthogonal increments on the real line in terms of its variogram or its construction. Our findings are a little bit surprising: this subclass is big in terms of the variogram, and on the other hand, it is relatively “small” according to a simple construction. In particular, every such process with Gaussian increments can be simply constructed from Brownian motion. Using the characterizations we obtain a series expansion of the stochastic process with orthogonal increments.
IL-18 Does not Increase Allergic Airway Disease in Mice When Produced by BCG
Authors: Amniai L. , Biet F. , Marquillies P. , Locht C. , Pestel J. , Tonnel A.-B. , Duez C.
Published: February 2008

Whilst BCG inhibits allergic airway responses in murine models, IL-18 has adversary effects depending on its environment. We therefore constructed a BCG strain producing murine IL-18 (BCG-IL-18) and evaluated its efficiency to prevent an asthma-like reaction in mice. BALB/cByJ mice were sensitized (day (D) 1 and D10) by intraperitoneal injection of ovalbumin (OVA)-alum and primary (D2022) and secondary (D62, 63) challenged with OVA aerosols. BCG or BCG-IL-18 were intraperitonealy administered 1 hour before each immunization (D1 and D10). BCG-IL-18 and BCG were shown to similarly inhibit the development of AHR, mucus production, eosinophil influx, and local Th2 cytokine production in BAL, both after the primary and secondary challenge. These data show that IL-18 did not increase allergic airway responses in the context of the mycobacterial infection, and suggest that BCG-IL-18 and BCG are able to prevent the development of local Th2 responses and therefore inhibit allergen-induced airway responses even after restimulation.
Host Specificity in the Parasitic PlantCytinus hypocistis
Authors: Thorogood C. J. , Hiscock S. J.
Published: February 2008

Host specificity in the parasitic plantCytinus hypocistiswas quantified at four sites in the Algarve region of Portugal from 2002 to 2007. The parasite was found to be locally host specific, and only two hosts were consistently infected:Halimium halimifoliumandCistus monspeliensis.C. hypocistisdid not infect hosts in proportion to their abundance; at three sites, 100% of parasites occurred onH. halimifoliumwhich represented just 42.4%, 3% and 19.7% of potential hosts available, respectively. At the remaining site, whereH. halimifoliumwas absent, 100% of parasites occurred onC. monspeliensiswhich represented 81.1% of potential hosts available. Other species of potential host were consistently uninfected irrespective of their abundance. Ecological niche divergence of host plantsH. halimifoliumandC. monspeliensismay isolate host-specific races ofC. hypocistis, thereby potentially driving allopatric divergence in this parasitic plant.
A General Iterative Method for Equilibrium Problems and Fixed Point Problems in Hilbert Spaces
Authors: Shang Meijuan , Su Yongfu , Qin Xiaolong
Published: February 2008

We introduce a general iterative scheme by the viscosity approximation method for finding a common element of the set of solutions of an equilibrium problem and the set of fixed points of a nonexpansive mapping in a Hilbert space. Our results improve and extend the corresponding ones announced by S. Takahashi and W. Takahashi in 2007, Marino and Xu in 2006, Combettes and Hirstoaga in 2005, and many others.
Stage-Structured ImpulsiveSIModel for Pest Management
Authors: Shi Ruiqing , Chen Lansun
Published: February 2008

AnSIepidemic model with stage structure is investigated. In the model, impulsive biological control is taken, that is, we release infected pests to the field at a fixed time periodically. We get a sufficient condition for the global asymptotical stability of the pest-eradication periodic solution(0,0,I˜(t)), and a condition for the permanence of the system. At last, a brief discussion shows that our results will be helpful for pest management.
What Else Is the Evolution of PSO Telling Us?
Authors: Dioşan Laura , Oltean Mihai
Published: February 2008

Evolutionary algorithms (EAs) can be used in order to design particle swarm optimization (PSO) algorithms that work, in some cases, considerably better than the human‐designed ones. By analyzing the evolutionary process of designing PSO algorithms, we can identify different swarm phenomena (such as patterns or rules) that can give us deep insights about the swarm behavior. The rules that have been observed can help us design better PSO algorithms for optimization. We investigate and analyze swarm phenomena by looking into the process of evolving PSO algorithms. Several test problems have been analyzed in the experiments and interesting facts can be inferred from the strategy evolution process (the particle quality could influence the update order, some particles are updated more frequently than others, the initial swarm size is not always optimal).
Design and Implementation of a Hardware Module for MIMO Decoding in a 4G Wireless Receiver
Authors: Jiménez-Pacheco Alberto , Fernández-Herrero Ángel , Casajús-Quirós Javier
Published: February 2008

Future 4th Generation (4G) wireless multiuser communication systems will have to provide advanced multimedia services to an increasing number of users, making good use of the scarce spectrum resources. Thus, 4G system design should pursue both higher‐transmission bit rates and higher spectral efficiencies. To achieve this goal, multiple antenna systems are called to play a crucial role. In this contribution we address the implementation in FPGAs of a multiple‐input multiple‐output (MIMO) decoder embedded in a prototype of a 4G mobile receiver. This MIMO decoder is part of a multicarrier code‐division multiple‐access (MC‐CDMA) radio system, equipped with multiple antennas at both ends of the link, that is able to handle up to 32 users and provides raw transmission bit‐rates up to 125 Mbps. The task of the MIMO decoder is to appropriately combine the signals simultaneously received on all antennas to construct an improved signal, free of interference, from which to estimate the transmitted symbols. A comprehensive explanation of the complete design process is provided, including architectural decisions, floating‐point to fixed‐point translation, and description of the validation procedure. We also report implementation results using FPGA devices of the Xilinx Virtex‐4 family.
Rate‐Distortion Optimized Frame Dropping for Multiuser Streaming and Conversational Videos
Authors: Tu Wei , Chakareski Jacob , Steinbach Eckehard
Published: February 2008

We consider rate‐distortion optimized strategies for dropping frames from multiple conversational and streaming videos sharing limited network node resources. The dropping strategies are based on side information that is extracted during encoding and is sent along the regular bitstream. The additional transmission overhead and the computational complexity of the proposed frame dropping schemes are analyzed. Our experimental results show that a significant improvement in end‐to‐end performance is achieved compared to priority‐based random early dropping.
A Survey of Insulin-Dependent Diabetes—Part I: Therapies and Devices
Authors: Takahashi Daisuke , Xiao Yang , Hu Fei , Lewis Michael
Published: February 2008

This paper surveys diabetes therapies from telemedicine viewpoint. In type 1 diabetes therapies, the exogenous insulin replacement is generally considered as a primary treatment. However, the complete replacement of exogenous insulin is still a challenging issue because of its complexity of modeling the dynamics, which is typically modeled nonlinearly. On the other hand, thanks to the progress of medical devices, currently the diabetes therapies are being automated. These medical devices include automated insulin pumps and blood glucose sensors. Insulin pumps are designed to create artificial insulin perfusion while they largely rely on the blood glucose profile measurements and these measurements are achieved by one or more blood glucose sensors. The blood glucose measurements are also important for the insulin-dependent diabetes therapies. An insulin pump along with sensors establishes a good feedback system providing the appropriate amount of the exogenous insulin on demand. Controlling the amount of exogenous insulin to suppress the blood glucose levels requires complicated computations. This paper mostly explains both type 1 and 2 diabetes and their mechanisms accompanied by descriptions of diabetes therapy and medical devices currently utilized in the therapy.
Role of Peoxisome Proliferator Activator Receptor γ on Blood Retinal Barrier Breakdown
Authors: Yanagi Yasuo
Published: February 2008

The retinal vessels have two barriers: the retinal pigment epithelium and the retinal vascular endothelium. Each barrier exhibits increased permeability under various pathological conditions. This condition is referred to as blood retinal barrier (BRB) breakdown. Clinically, the most frequently encountered condition causing BRB breakdown is diabetic retinopathy. In recent studies, inflammation has been linked to BRB breakdown and vascular leakage in diabetic retinopathy. Biological support for the role of inflammation in early diabetes is the adhesion of leukocytes to the retinal vasculature (leukostasis) observed in diabetic retinopathy. PPARγ is a member of a ligand‐activated nuclear receptor superfamily and plays a critical role in a variety of biological processes, including adipogenesis, glucose metabolism, angiogenesis, and inflammation. There is now strong experimental evidence to support the theory that PPARγ inhibits diabetes‐induced retinal leukostasis and leakage, playing an important role in the pathogenesis of diabetic retinopathy. Therapeutic targeting of PPARγ may be beneficial to diabetic retinopathy.
High‐Performance Timing‐Driven Rank Filter
Authors: Szántó Péter , Szedő Gábor , Fehér Béla
Published: February 2008

This paper presents an FPGA implementation of a high‐performance rank filter for video and image processing. The architecture exploits the features of current FPGAs and offers tradeoffs between complexity and performance. By maximizing the operating frequency, the complexity of the filter structure can be considerably reduced compared to previous 2D architectures.
Computation of a Reference Model for Robust Fault Detection and Isolation Residual Generation
Authors: Mazars Emmanuel , Jaimoukha Imad M. , Li Zhenhai
Published: February 2008

This paper considers matrix inequality procedures to address the robust fault detection and isolation (FDI) problem for linear time‐invariant systems subject to disturbances, faults, and polytopic or norm‐bounded uncertainties. We propose a design procedure for an FDI filter that aims to minimize a weighted combination of the sensitivity of the residual signal to disturbances and modeling errors, and the deviation of the faults to residual dynamics from a fault to residual reference model, using theℋ∞‐norm as a measure. A key step in our procedure is the design of an optimal fault reference model. We show that the optimal design requires the solution of a quadratic matrix inequality (QMI) optimization problem. Since the solution of the optimal problem is intractable, we propose a linearization technique to derive a numerically tractable suboptimal design procedure that requires the solution of a linear matrix inequality (LMI) optimization. A jet engine example is employed to demonstrate the effectiveness of the proposed approach.
Structural and Functional Genomics of Tomato
Authors: Barone Amalia , Chiusano Maria Luisa , Ercolano Maria Raffaella , Giuliano Giovanni , Grandillo Silvana , Frusciante Luigi
Published: February 2008

Tomato (Solanum lycopersicumL.) is the most intensively investigated Solanaceous species both in genetic and genomics studies. It is a diploid species with a haploid set of 12 chromosomes and a small genome (950 Mb). Based on the detailed knowledge on tomato structural genomics, the sequencing of the euchromatic regions started in the year 2005 as a common effort of different countries. The manuscript focuses on markers used for tomato, on mapping efforts mainly based on exploitation of natural biodiversity, and it gives an updated report on the international sequencing activities. The principal tools developed to explore the function of tomato genes are also summarized, including mutagenesis, genetic transformation, and transcriptome analysis. The current progress in bioinformatic strategies available to manage the overwhelming amount of data generated from different tomato “omics” approaches is reported, and emphasis is given to the effort of producing a computational workbench for the analysis of the organization, as well as the functionality and evolution of the Solanaceae family.
Pancreaticoduodenectomy: Volume is not Associated with Outcome within an Academic Health Care System
Authors: Schell Micheal T. , Barcia Anthony , Spitzer Austin L. , Harris Hobart W.
Published: February 2008

Hypothesis. Smaller and lower-volume hospitals can attain surgical outcomes similar to high-volume centers if they incorporate the expertise and health care pathways of high-volume centers. Setting. The academic tertiary care center, Moffit-Long Hospital (ML); the community-based Mount Zion Hospital (ZION); the San Francisco County General Hospital (SFGH); and the Veterans Affairs Medical Center of San Francisco (VAMC). Patients. 369 patients who underwent pancreaticoduodenectomy between October 1989 and June 2003 at the University of California, San Francisco (UCSF) affiliated hospitals. Interventions. Pancreaticoduodenectomy. Design. Retrospective chart review. To correct for the potentially confounding effect of small case volumes and event rates, data for SFGH, VAMC, and ZION was combined (Small Volume Hospital Group; SVHG) and compared against data for ML. Main Outcome Measures. Complication rates; three-year and five-year survival rates. Results. The average patient age and health, as determined by ASA score, were similar between ML and the SVHG. The postoperative complication rate did not differ significantly between ML and the SVGH (58.8% versus 63.1%). Patients that experienced a complication averaged 2.5 complications in both groups. The perioperative mortality rate was 4% for patients undergoing pancreaticoduodenectomy at either ML or the SVGH. Although the 3-year survival rate for patients with adenocarcinoma of the pancreas was nearly twice as high at ML (31.2% versus 18.3% at SVHG), there was no significant difference in the 5-year survival rates (19% at ML versus 18.3% at SVHG). Conclusions. Low-volume hospitals can achieve similar outcomes to high-volume tertiary care centers provided they import the expertise and care pathways necessary for improved results.
IκB kinase β inhibition induces cell death in Imatinib-resistant and T315I Dasatinib-resistant BCR-ABL+ cells
Authors: Duncan Elizabeth A. , Goetz Christine A. , Stein Sarah J. , Mayo Katie J. , Skaggs Brian J. , Ziegelbauer Karl , Sawyers Charles L. , Baldwin Albert S.
Published: February 2008

Chronic myelogenous leukemia is a malignant disease of the hematopoietic stem cell compartment, which is characterized by expression of the BCR-ABL fusion protein. Expression of BCR-ABL allows myeloid cells to grow in the absence of the growth factors interleukin-3 and granulocyte-macrophage colony-stimulating factor. The tyrosine kinase activity of BCR-ABL constitutively activates signaling pathways associated with Ras and its downstream effectors and with the Jak/STAT pathway. Additionally, we reported previously that BCR-ABL activates the transcription factor nuclear factor-κB (NF-κB) in a manner dependent on Ras and that inhibition of NF-κB by expression of a modified form of IκBα blocked BCR-ABL-driven tumor growth in a xenograft model. Here, we show that a highly specific inhibitor of IκB kinase β, a key upstream regulator of the NF-κB pathway, induces growth suppression and death in cells expressing wild-type, Imatinib-resistant, or the T315I Imatinib/Dasatinib-resistant forms of BCR-ABL. Cell cycle variables were not affected by this compound. These data indicate that blockage of BCR-ABL-induced NF-κB activation via IκB kinase β inhibition represents a potential new approach for treatment of Imatinib- or Dasatinib-resistant forms of chronic myelogenous leukemia. [Mol Cancer Ther 2008;7(2):391–7]
Potent antitumor effects of ZD6474 on neuroblastoma via dual targeting of tumor cells and tumor endothelium
Authors: Beaudry Paul , Nilsson Monique , Rioth Matthew , Prox Daniela , Poon David , Xu Lanwei , Zweidler-Mckay Patrick , Ryan Anderson , Folkman Judah , Ryeom Sandra , Heymach John
Published: February 2008

Among children with relapsed or refractory neuroblastoma, the prognosis is poor and novel therapeutic strategies are needed to improve long-term survival. As with other solid tumors, high vascular density within neuroblastoma is associated with advanced disease, and therapeutic regimens directed against the tumor vasculature may provide clinical benefit. The receptor tyrosine kinase RET is widely expressed in neuroblastoma and is known to activate key signal transduction pathways involved in tumor cell survival and progression including Ras/mitogen-activated protein kinase and phosphatidylinositol 3-kinase/Akt. We investigated the effect of dual targeting of tumor cells and tumor endothelium with ZD6474, a small-molecule tyrosine kinase inhibitor of vascular endothelial growth factor (VEGF) receptor 2, epidermal growth factor receptor, and RET. ZD6474 inhibited the phosphorylation of RET in neuroblastoma cells and had a direct effect on tumor cell viability in seven neuroblastoma cell lines. In a human neuroblastoma xenograft model, ZD6474 inhibited tumor growth by 85% compared with treatment with vehicle alone. In contrast, no significant inhibition of tumor growth was observed after treatment with bevacizumab, an antihuman VEGF monoclonal antibody, or the epidermal growth factor receptor inhibitor erlotinib, either alone or in combination. Immunohistochemical analysis showed that ZD6474 treatment led to an increase in endothelial cell apoptosis along with inhibition of VEGF receptor-2 activation on tumor endothelium. In conclusion, dual targeting of tumor cells, potentially through RET inhibition, and tumor vasculature with ZD6474 leads to potent antitumor effects. This approach merits further investigation for patients with neuroblastoma. [Mol Cancer Ther 2008;7(2):418–24]
A cell-active inhibitor of mitogen-activated protein kinase phosphatases restores paclitaxel-induced apoptosis in dexamethasone-protected cancer cells
Authors: Vogt Andreas , McDonald Peter R. , Tamewitz Aletheia , Sikorski Rachel P. , Wipf Peter , Skoko John J. , Lazo John S.
Published: February 2008

Mitogen-activated protein kinase phosphatase (MKP)-1 is a dual-specificity phosphatase that negatively regulates the activity of mitogen-activated kinases and that is overexpressed in human tumors. Contemporary studies suggest that induction of MKP-1 during chemotherapy may limit the efficacy of clinically used antineoplastic agents. Thus, MKP-1 is a rational target to enhance anticancer drug activity, but suitable small-molecule inhibitors of MKP-1 are currently unavailable. Here, we have used a high-content, multiparameter fluorescence-based chemical complementation assay for MKP activity in intact mammalian cells to evaluate the cellular MKP-1 and MKP-3 inhibitory activities of four previously described, quinone-based, dual-specificity phosphatase inhibitors, that is, NSC 672121, NSC 95397, DA-3003-1 (NSC 663284), and JUN-1111. All compounds induced formation of reactive oxygen species in mammalian cells, but only one (NSC 95397) inhibited cellular MKP-1 and MKP-3 with an IC50 of 13 μmol/L. Chemical induction of MKP-1 by dexamethasone protected cells from paclitaxel-induced apoptosis but had no effect on NSC 95397. NSC 95397 phenocopied the effects of MKP-1 small inhibitory RNA by reversing the cytoprotective effects of dexamethasone in paclitaxel-treated cells. Isobologram analysis revealed synergism between paclitaxel and NSC 95397 only in the presence of dexamethasone. The data show the power of a well-defined cellular assay for identifying cell-active inhibitors of MKPs and support the hypothesis that small-molecule inhibitors of MKP-1 may be useful as antineoplastic agents under conditions of high MKP-1 expression. [Mol Cancer Ther 2008;7(2):330–40]
Eicosapentaenoic Acid Could Permit Maintenance of the Original Ribavirin Dose in Chronic Hepatitis C Virus Patients during the First 12 Weeks of Combination Therapy with Pegylated Interferon-α and Ribavirin
Authors: Takaki Shintaro , Kawakami Yoshiiku , Imamura Michio , Aikata Hiroshi , Takahashi Shoichi , Ishihara Hiroto , Tsuji Keiji , Aimitsu Shiomi , Kawakami Hiroiku , Nakanishi Toshio , Kitamoto Mikiya , Moriya Takashi , Satoh Kenichi , Chayama Kazuaki
Published: February 2008

Objective: To evaluate the efficacy of eicosapentaenoic acid (EPA) against ribavirin (RBV)-associated hemolytic anemia during the first 12 weeks in chronic hepatitis C virus (HCV) combination therapy. Methods: This study was a prospective open-label, randomized controlled trial. 100 HCV patients were randomized to either the EPA group (n = 49) or non-EPA group (n = 51) who received combination therapy with or without EPA. We compared the changes in hemoglobin level and RBV plasma concentrations at week 12 in each group with RBV dose reduction rate and performed multivariate analysis to identify independent variables associated with RBV dose reduction. Results: 8 patients (17%) in the EPA group and 20 patients (29%) in the non-EPA group required RBV dose reduction, respectively. The cumulative RBV reduction rate was significantly lower in the EPA group than in the non-EPA group (p = 0.017), while the decrease of hemoglobin and RBV plasma concentrations from baseline was not significantly different. However, in the multivariate analysis, treatment with EPA showed significant variables for the reduction of RBV dose (odds ratio 3.235, p = 0.023). Conclusion: EPA could prevent the RBV dose reduction during the first 12 weeks in combination therapy, although further large-scale double-blind randomized controlled trials are required.
Potentiation of Potassium Currents by Beta-Adrenoceptor Agonists in Human Urinary Bladder Smooth Muscle Cells: A Possible Electrical Mechanism of Relaxation
Authors: Takemoto Jun , Masumiya Haruko , Nunoki Kazuo , Sato Takeya , Nakagawa Haruo , Ikeda Yoshihiro , Arai Yoichi , Yanagisawa Teruyuki
Published: February 2008

We examined the effects of β-adrenoceptor agonists on the membrane currents of smooth muscle cells from the human urinary bladder using a whole-cell patch clamp to investigate the involvement of Ca2+-activated K+ (KCa) channels in relaxation by β-adrenergic agonists. With 0.05 mmol/l EGTA in the patch pipette, depolarizing pulses evoked outward rectifying currents. Isoproterenol (1 µmol/l) significantly increased the membrane currents by 75% at +80 mV with 0.05 mmol/l EGTA pipette solution. BRL 37344 (1 µmol/l) significantly increased the membrane currents by 44% at +80 mV. Iberiotoxin (100 nmol/l) significantly decreased the membrane currents by 60% at +80 mV. In the presence of iberiotoxin, the potentiation of the outward currents by isoproterenol was greatly suppressed and, in the presence of iberiotoxin and apamin (1 µmol/l), the potentiation by isoproterenol was totally abolished. On the other hand, with 5 mmol/l EGTA pipette solution, depolarizing pulses evoked smaller outward currents. Isoproterenol (1 µmol/l) did not change the membrane currents with 5 mmol/l EGTA pipette solution. The real-time PCR analysis revealed the expression of β2-adrenoceptors in the cells. These results suggest that Ca2+-activated and iberiotoxin- and apamin-sensitive currents via both large-conductance and small-conductance KCa channels could be increased by stimulation of β2-adrenoceptors.
Investigation of the Anti-Inflammatory Potential of Aloe vera Gel (97.5%) in the Ultraviolet Erythema Test
Authors: Reuter J. , Jocher A. , Stump J. , Grossjohann B. , Franke G. , Schempp C.M.
Published: February 2008

Background:Aloe vera is a natural product that is frequently used in soothing skin care products such as aftersun lotions. In the present study we aimed to explore the anti-inflammatory potential of a highly concentrated A. vera gel in the UV erythema test in vivo. Methods: 40 volunteers with skin types II and III were included in the randomized, double-blind, placebo-controlled, phase III monocenter study. Test areas on the back were irradiated with the 1.5-fold minimal erythema dose of UVB. Subsequently, the test areas were treated occlusively on 2 subsequent days with A. vera gel (97.5%), the positive controls (0.25% prednicarbate, 1% hydrocortisone in placebo gel and 1% hydrocortisone cream) and a placebo gel. Erythema values were determined photometrically after 24 and 48 h. Results:A. vera gel (97.5%) significantly reduced UV-induced erythema after 48 h, being superior to 1% hydrocortisone in placebo gel. In contrast, 1% hydrocortisone in cream was more efficient than A. vera gel. Conclusions: In this study after 48 h the A. vera gel (97.5%) displayed some anti-inflammatory effects superior to those of 1% hydrocortisone in placebo gel. The A. vera gel tested here might be useful in the topical treatment of inflammatory skin conditions such as UV-induced erythema.
Epidermal Ceramidase Activity Regulates Epidermal Desquamation via Stratum Corneum Acidification
Authors: Houben E. , Hachem J.P. , De Paepe K. , Rogiers V.
Published: February 2008

The acidic pH of the outer surface of the mammalian skin plays several important roles in the epidermal barrier function. The 2 endogenous pathways that are currently known to elicit this acidic pH are the generation of free fatty acids from phospholipids and the exchange of protons for sodium ions by non-energy-dependent sodium-proton exchangers. In this study, we propose a third endogenous pathway, i.e. epidermal ceramidase activity, generating free fatty acids from ceramides. By topical application of N-oleylethanolamine, a well-known ceramidase inhibitor, we could demonstrate a significant increase in the stratum corneum pH and a corresponding decrease in the epidermal free fatty acid content. Moreover, we could show that the resulting change in the apparent skin pH also provoked a delay in early barrier recovery and an increased epidermal desquamation, corresponding to earlier observations made for the already known endogenous mechanisms.
Feeding Behavior in Rats Subjected to Gastrectomy or Gastric Bypass Surgery
Authors: Furnes M.W. , Stenström B. , Tømmerås K. , Skoglund T. , Dickson S.L. , Kulseng B. , Zhao C.-M. , Chen D.
Published: February 2008

Background/Aim: Gastric bypass (GB) is usually designed to restrict food intake and to induce malabsorption. Gastric hormones have been thought to play a role in the regulation of food intake and body weight. The aim of the present study was to analyze feeding behavior after total gastrectomy (Gx) or GB in rats. Methods: Animals were subjected to Gx, GB, or sham operations. Eating and drinking behaviors after surgeries were assessed by a comprehensive laboratory animal monitoring system. Gastric hormones were measured by radioimmunoassay and energy density in feces by adiabatic bomb calorimeter. Results: Compared with sham operation, both Gx and GB reduced the body weight as measured during 3–8 weeks postoperatively, which was associated with increased energy expenditure per 100 g body weight. Daily accumulated food intake and meal size (during nighttime) were reduced following Gx, but not GB. The water intake (during daytime) was increased after Gx and GB. The energy density in feces was unchanged. Serum concentrations of ghrelin, obestatin, leptin, gastrin, and pancreastatin were greatly reduced after Gx. Conclusions: Control of food intake and meal size was independent of the food reservoir function of the stomach. Surgical depletion of gastric hormones is associated with reduced meal size, but increased water intake.
The Effects of Lipopolysaccharide-Induced Reactive Oxygen Species Were Blunted by Calcium Oxalate in Renal Tubular Epithelial Cells
Authors: Borges F.T. , Garofalo A.S. , Dalboni M.A. , Abreu N.P. , Michelacci Y.M. , Schor N.
Published: February 2008

Background/Aim: Previously we demonstrated that calcium oxalate (CaOx) in LLC-PK1 cells and oxalate in MDCK cells induce tubular damage and greater glycosaminoglycan synthesis. We test the hypothesis that reactive oxygen species (ROS) and prostaglandins mediate these effects. Methods: LLC-PK1 and MDCK cells were exposed to graded concentrations of CaOx, oxalate or both. Glycosaminoglycan synthesis was analyzed through metabolic labeling and gel electrophoresis. Cell permeability and lipid peroxidation were assessed by lactate dehydrogenase release and malondialdehyde levels. Hydrogen peroxide and superoxide anion were analyzed using 2′,7′-dichlorofluorescein and luminol. Cyclooxygenase-2 expression and prostaglandin E2 production were assessed by RT-PCR and ELISA, respectively. Results: In LLC-PK1 cells exposed to CaOx, we observed increased cell permeability, no induction of ROS or lipid peroxidation, inability to produce lipopolysaccharide-induced ROS and increases in prostaglandin E2. Indomethacin used alone increased glycosaminoglycan synthesis but did not potentiate CaOx-induced effects. In MDCK cells exposed to oxalate we observed increased cell permeability, ROS production only at higher concentrations and inability to produce lipopolysaccharide-induced ROS. Indomethacin alone had no effect but increased oxalate-induced glycosaminoglycan synthesis. Conclusions: Prostaglandins modulate endogenous production of glycosaminoglycans in LLC-PK1 cells, as well as regulate oxalate-induced glycosaminoglycan synthesis in MDCK cells. Rather than increasing, CaOx and oxalate blunted lipopolysaccharide-induced ROS production. We could speculate that patients with recurrent nephrolithiasis may lose antimicrobial protection induced by ROS during infections.