bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gemcitabine intercellular diffusion mediated by gap junctions: new implications for cancer therapy
Authors: Cottin Sylvine , Ghani Karim , de Campos-Lima Pedro Otavio , Caruso Manuel 
Published: June 2010

AbstractBackgroundSolid tumors are often poorly vascularized, with cells that can be 100 μm away from blood vessels. These distant cells get less oxygen and nutrients and are exposed to lower doses of chemotherapeutic agents. As gap junctions allow the passage of small molecules between cells, we tested the possibility that the chemotherapeutic agent gemcitabine can diffuse through gap junctions in solid tumors.ResultsWe first showed with a dye transfer assay that the glioblastoma and the osteosarcoma cells used in this study have functional gap junctions. These cells were genetically engineered to express the herpes simplex virus thymidine kinase (TK), and induced a "bystander effect" as demonstrated by the killing of TK-negative cells in presence of the nucleoside analogue ganciclovir (GCV). The ability of gemcitabine to induce a similar bystander effect was then tested by mixing cells treated with 3 μM gemcitabine for 24 hours with untreated cells at different ratios. In all cell lines tested, bystander cells were killed with ratios containing as low as 5% treated cells, and this toxic effect was reduced in presence of α-glycyrrhetinic acid (AGA), a specific gap junction inhibitor. We also showed that a 2- or a 24-hour gemcitabine treatment was more efficient to inhibit the growth of spheroids with functional gap junctions as compared to the same treatment made in presence of AGA. Finally, after a 24-hour gemcitabine treatment, the cell viability in spheroids was reduced by 92% as opposed to 51% in presence of AGA.ConclusionThese results indicate that gemcitabine-mediated toxicity can diffuse through gap junctions, and they suggest that gemcitabine treatment could be more efficient for treating solid tumors that display gap junctions. The presence of these cellular channels could be used to predict the responsiveness to this nucleoside analogue therapy.
Extracellular ATP and the P2X7receptor in astrocyte-mediated motor neuron death: implications for amyotrophic lateral sclerosis
Authors: Gandelman Mandi , Peluffo Hugo , Beckman Joseph S , Cassina Patricia , Barbeito Luis 
Published: June 2010

Abstract

Background
During pathology of the nervous system, increased extracellular ATP acts both as a cytotoxic factor and pro-inflammatory mediator through P2X7 receptors. In animal models of amyotrophic lateral sclerosis (ALS), astrocytes expressing superoxide dismutase 1 (SOD1G93A) mutations display a neuroinflammatory phenotype and contribute to disease progression and motor neuron death. Here we studied the role of extracellular ATP acting through P2X7 receptors as an initiator of a neurotoxic phenotype that leads to astrocyte-mediated motor neuron death in non-transgenic and SOD1G93A astrocytes.

Methods
We evaluated motor neuron survival after co-culture with SOD1G93A or non-transgenic astrocytes pretreated with agents known to modulate ATP release or P2X7 receptor. We also characterized astrocyte proliferation and extracellular ATP degradation.

Results
Repeated stimulation by ATP or the P2X7-selective agonist BzATP caused astrocytes to become neurotoxic, inducing death of motor neurons. Involvement of P2X7 receptor was further confirmed by Brilliant blue G inhibition of ATP and BzATP effects. In SOD1G93A astrocyte cultures, pharmacological inhibition of P2X7 receptor or increased extracellular ATP degradation with the enzyme apyrase was sufficient to completely abolish their toxicity towards motor neurons. SOD1G93A astrocytes also displayed increased ATP-dependent proliferation and a basal increase in extracellular ATP degradation.

Conclusions
Here we found that P2X7 receptor activation in spinal cord astrocytes initiated a neurotoxic phenotype that leads to motor neuron death. Remarkably, the neurotoxic phenotype of SOD1G93A astrocytes depended upon basal activation the P2X7 receptor. Thus, pharmacological inhibition of P2X7 receptor might reduce neuroinflammation in ALS through astrocytes.
Bayes-LQAS: classifying the prevalence of global acute malnutrition
Authors: Olives Casey , Pagano Marcello 
Published: June 2010

AbstractLot Quality Assurance Sampling (LQAS) applications in health have generally relied on frequentist interpretations for statistical validity. Yet health professionals often seek statements about the probability distribution of unknown parameters to answer questions of interest. The frequentist paradigm does not pretend to yield such information, although a Bayesian formulation might. This is the source of an error made in a recent paper published in this journal. Many applications lend themselves to a Bayesian treatment, and would benefit from such considerations in their design. We discuss Bayes-LQAS (B-LQAS), which allows for incorporation of prior information into the LQAS classification procedure, and thus shows how to correct the aforementioned error. Further, we pay special attention to the formulation of Bayes Operating Characteristic Curves and the use of prior information to improve survey designs. As a motivating example, we discuss the classification of Global Acute Malnutrition prevalence and draw parallels between the Bayes and classical classifications schemes. We also illustrate the impact of informative and non-informative priors on the survey design. Results indicate that using a Bayesian approach allows the incorporation of expert information and/or historical data and is thus potentially a valuable tool for making accurate and precise classifications.
Multiplex Amplification Refractory Mutation System Polymerase Chain Reaction (ARMS-PCR) for diagnosis of natural infection with canine distemper virus
Authors: Chulakasian Songkhla , Lee Min-Shiuh , Wang Chi-Young , Chiou Shyan-Song , Lin Kuan-Hsun , Lin Fong-Yuan , Hsu Tien-Huan , Wong Min-Liang , Chang Tien-Jye , Hsu Wei-Li 
Published: June 2010

AbstractBackgroundCanine distemper virus (CDV) is present worldwide and produces a lethal systemic infection of wild and domesticCanidae. Pre-existing antibodies acquired from vaccination or previous CDV infection might interfere the interpretation of a serologic diagnosis method. In addition, due to the high similarity of nucleic acid sequences between wild-type CDV and the new vaccine strain, current PCR derived methods cannot be applied for the definite confirmation of CD infection. Hence, it is worthy of developing a simple and rapid nucleotide-based assay for differentiation of wild-type CDV which is a cause of disease from attenuated CDVs after vaccination. High frequency variations have been found in the region spanning from the 3'-untranslated region (UTR) of the matrix (M) gene to the fusion (F) gene (designated M-F UTR) in a few CDV strains. To establish a differential diagnosis assay, an amplification refractory mutation analysis was established based on the highly variable region on M-F UTR and F regions.ResultsSequences of frequent polymorphisms were found scattered throughout the M-F UTR region; the identity of nucleic acid between local strains and vaccine strains ranged from 82.5% to 93.8%. A track of AAA residue located 35 nucleotides downstream from F gene start codon highly conserved in three vaccine strains were replaced with TGC in the local strains; that severed as target sequences for deign of discrimination primers. The method established in the present study successfully differentiated seven Taiwanese CDV field isolates, all belonging to the Asia-1 lineage, from vaccine strains.ConclusionsThe method described herein would be useful for several clinical applications, such as confirmation of nature CDV infection, evaluation of vaccination status and verification of the circulating viral genotypes.
Interleukins 4 and 13 modulate gene expression and promote proliferation of primary human tenocytes
Authors: Courneya Jean-Paul , Luzina Irina G , Zeller Cynthia B , Rasmussen Jeffrey F , Bocharov Alexander , Schon Lew C , Atamas Sergei P 
Published: June 2010

Abstract

Background
Tendon disorders (tendinopathies) pose serious biomedical and socioeconomic problems. Despite diverse treatment approaches, the best treatment strategy remains unclear. Surgery remains the last resort because of the associated morbidity and inconsistent outcomes. We hypothesized that, similar to fibroblasts in various organs, tendon fibroblasts (tenocytes) might be responsive to stimulation with interleukins (ILs), particularly IL-4 and IL-13. These two cytokines share sequence homology, receptor chains and functional effects, including stimulation of fibrogenesis. It is unknown whether tenocytes are responsive to stimulation with IL-4 or IL-13. If true, local use of these cytokines might be used to facilitate tendon repair in patients with tendinopathies or used for tendon tissue-engineering approaches to facilitate tenocyte growth on scaffolds in culture.

Results
Tendon tissues that would normally be discarded were obtained during reconstructive surgery procedures performed for clinical indications. Primary tenocytes were derived from Achilles, posterior tibial, flexor digitorum longus and flexor hallucis longus tendon tissue samples. Reverse transcriptase quantitative PCR (RT-qPCR) experiments revealed that mRNAs for the receptor (R) chains IL-4Rα, IL-13Rα1 and IL-13Rα2, but not the common γ-chain were present in all tested tendon tissues and in cultured tenocytes. Levels of IL-13R chain mRNAs were significantly higher than those of IL-4R mRNA. The cultures responded, in a dose-dependent fashion, to stimulation with recombinant human IL-4 or IL-13, by increasing proliferation rates 1.5 to 2.0-fold. The mRNA levels of 84 genes related to cell cycle regulation were measured by RT-qPCR after 6 h and 24 h of activation. The expression levels of several genes, notably CDK6 and CDKN2B changed more than twofold. In contrast to their effects on proliferation, stimulation with IL-4 or IL-13 had little if any effect on the levels of collagen mRNA or protein in cultured primary tenocytes. The mRNA levels of 84 other genes related to extracellular matrix and cell adhesion were also measured by RT-qPCR; expression of only five genes was consistently changed.

Conclusions
Stimulation with IL-4 or IL-13 could be used to facilitate tendon repair in vivo or to aid in tendon tissue engineering, through stimulation of tenocyte proliferation.
Risk factors for radiographic progression in psoriatic arthritis: subanalysis of the randomized controlled trial ADEPT
Authors: Gladman Dafna D , Mease Philip J , Choy Ernest HS , Ritchlin Christopher T , Perdok Renee J , Sasso Eric H 
Published: June 2010

Abstract
Introduction
To identify independent predictors of radiographic progression in psoriatic arthritis (PsA) for patients treated with adalimumab or placebo in the Adalimumab Effectiveness in PsA Trial (ADEPT).

Methods
Univariate analyses and multivariate linear regression analyses assessed risk for radiographic progression (change in modified total Sharp score, ΔmTSS > 0.5) from baseline to week 24 for C-reactive protein (CRP) and other baseline variables, and for 24-week time-averaged CRP (univariate analysis only). Subanalyses determined mean ΔmTSS for CRP subgroups. Analyses were post hoc, with observed data.

Results
One hundred and forty-four adalimumab-treated patients and 152 placebo-treated patients were assessed. Mean CRP was 64% lower by week 2 with adalimumab and essentially unchanged with placebo. Univariate analyses indicated that elevated CRP at baseline and time-averaged CRP were strongly associated with radiographic progression for placebo-treated patients but not for adalimumab-treated patients. Multivariate analysis confirmed that elevated baseline CRP was the only strong independent risk factor for radiographic progression (for CRP ≥1.0 mg/dl: odds ratio = 3.28, 95% confidence interval = 1.66 to 6.51, P < 0.001). Adalimumab treatment reduced risk of progression approximately fivefold. The difference between mean ΔmTSS for adalimumab versus placebo was greatest for patients with baseline CRP ≥2.0 mg/dl (-0.5 vs. 2.6).

Conclusions
Systemic inflammation in PsA, as indicated by elevated baseline CRP, was the only strong independent predictor of radiographic progression. This association was observed predominantly for placebo-treated patients. Adalimumab treatment substantially reduced the overall risk of radiographic progression, and provided greatest radiographic benefit for patients with the greatest CRP concentrations at baseline.

Trial Registration
Trial registration: NCT00195689.
Global fitness profiling of fission yeast deletion strains by barcode sequencing
Authors: Han Tian Xu , Xu Xing-Ya , Zhang Mei-Jun , Peng Xu , Du Li-Lin 
Published: June 2010

AbstractA genome-wide deletion library is a powerful tool for probing gene functions and one has recently become available for the fission yeastSchizosaccharomyces pombe. Here we use deep sequencing to accurately characterize the barcode sequences in the deletion library, thus enabling the quantitative measurement of the fitness of fission yeast deletion strains by barcode sequencing.
An Antiinflammatory and Reactive Oxygen Species Suppressive Effects of an Extract of Polygonum Cuspidatum Containing Resveratrol
Authors: Ghanim Husam , Sia Chang Ling , Abuaysheh Sanaa , Korzeniewski Kelly , Patnaik Priyanka , Marumganti Anuritha , Chaudhuri Ajay , Dandona Paresh 
Published: June 2010

Background: Resveratrol have been shown to exert an antiinflammatory and antiaging effects in vitro and in animal models.
Objective: The objective of the study was to investigate the effect of a Polygonum cuspidatum extract (PCE) containing resveratrol on oxidative and inflammatory stress in normal subjects.
Research Design and Methods: Two groups (10 each) of normal-weight healthy subjects were randomized to placebo or PCE containing 40 mg resveratrol daily for 6 wk. Fasting blood samples were obtained prior to and after treatment at 1, 3, and 6 wk. Mononuclear cells were prepared for reactive oxygen species generation, RNA isolation, nuclear extract, and total cell homogenate preparation. Indices of oxidative and inflammatory stress, suppressor of cytokine signaling-3, phosphotyrosine phosphatase-1B, jun-N-terminal kinase-1, and inhibitor of κB-kinase-β were measured by RT-PCR and Western blotting.
Results: The extract induced a significant reduction in reactive oxygen species generation, the expression of p47phox, intranuclear nuclear factor-κB binding, and the expression of jun-N-terminal kinase-1, inhibitor of κB-kinase-β, phosphotyrosine phosphatase-1B, and suppressor of cytokine signaling-3 in mononuclear cells when compared with the baseline and the placebo. PCE intake also suppressed plasma concentrations of TNF-α, IL-6, and C-reactive protein. There was no change in these indices in the control group given placebo.
Conclusions: The PCE-containing resveratrol has a comprehensive suppressive effect on oxidative and inflammatory stress.
Book Reviews
Authors: Lev Benjamin 
Published: June 2010

In Book Reviews, we review an extensive and diverse range of books. They cover theory and applications in operations research, statistics, management science, econometrics, mathematics, computers, and information systems. In addition, we include books in other fields that emphasize technical applications. However, we do not review software. To submit a book for review, please send it to me at the above address. Although we cannot review all books because of space limitations, we do list all books that we receive. We commission all book reviews and do not accept unsolicited reviews. To become a reviewer, please send me your name, address, and specific areas of expertise. We encourage readers to suggest books for review or to ask publishers to send copies of such books. The authors or editors of books that we review in this issue are Jonathan L. Gross and H. Paul Williams.
A Methodology for Improving Strategic Decisions in Social Systems with a Lack of Information
Authors: Verna Carlos , Škraba Andrej 
Published: June 2010

A Methodology for Improving Strategic Decisions in Social Systems with a Lack of Information
The design of strategies for social systems requires the use of qualitative information owing to the fact that quantitative information can be insufficient to solve the problems involved. The information that the specialists and the decision makers obtain is often incomplete and unreliable. Nevertheless, leaders have to make strategic decisions despite these deficiencies which should be based on the formal models (Kljajić et al. 2000; Škraba et al, 2003; Škraba et al 2007).
This paper describes a methodology elaborated to design the strategy of the city of Santa Cruz (on the Canary Islands). It has two main sections: the elaboration of a qualitative model and the use of System Dynamics. We combine them in a way that allows mixing qualitative and quantitative information to achieve a better understanding of the structure of the region, to know the tendencies of the present scenario and to estimate of the effects of alternative strategic decisions. We have obtained these results working with scarce quantitative information. This methodology may be applied to any social systems with similar characteristics.
The COMPRAM Methodology and Complex Societal Problems-an Analysis of the Case of Children Born of War
Authors: Mochmann Ingvill , DeTombe Dorien 
Published: June 2010

The COMPRAM Methodology and Complex Societal Problems-an Analysis of the Case of Children Born of War
During and after wars children are born where the father is a member of an occupation or peacekeeping force and the mother a local citizen. Securing the human rights of children born of war is often highly complex and involves researchers and practitioners from different disciplines. The Compram methodology on handling complex societal problems will be applied to analyse whether the methodology is suitable on this group of war-affected children. The Compram methodology is a multi disciplined, multi level, multi actor methodology based on the theory of societal complexity. The methodology gives guidelines to handle real life complex societal problems.
Development of a Web Application for Dynamic Production Scheduling in Small and Medium Enterprises
Authors: Kofjač Davorin , Knaflič Andrej , Kljajić Miroljub 
Published: June 2010

Development of a Web Application for Dynamic Production Scheduling in Small and Medium Enterprises
This article describes the development of a web-based dynamic job-shop scheduling system for small and medium enterprises. In large enterprises, scheduling is mainly performed with appropriate technology by human experts; many small and medium enterprises lack the resources to implement such a task. The main objective was to develop a cost-effective, efficient solution for job-shop scheduling in small and medium enterprises with an emphasis on accessibility, platform independence and ease of use. For these reasons, we decided to develop a web-based solution with the main emphasis on the development of an intelligent and dynamic user interface. The solution is built upon modular programming principles and enables dynamic scheduling on the basis of artificial intelligence, i.e. genetic algorithms. The solution has been developed as a standalone information system, which allows the management of virtually all scheduling activities through an administration panel. In addition, the solution covers the five main functionalities that completely support the scheduling process, i.e. making an inventory of resources available in the company, using it in the process of production planning, collecting data on production activities, distribution of up-to-date information and insight over events in the system.
Simulated Decision Learning in a Multiactor Setting
Authors: Asproth Viveca , Holmberg Stig , Löfstedt Ulrica 
Published: June 2010

Simulated Decision Learning in a Multiactor Setting
The idea of decision analysis-and subsequent learning from the outcomes-is old within Operational Research. Here this approach to continuous improvement of decision outcomes is put one step further within the area of crisis and disaster management. This is done by introducing multiactors making simultaneous decisions with just partial information about each other. Further, decision outcomes are achieved from a simulation model rather than from the real object system.
Error calibration of quasi-geoidal, normal and ellipsoidal heights of Sweden using variance component estimation
Authors: Eshagh Mehdi 
Published: June 2010

Error calibration of quasi-geoidal, normal and ellipsoidal heights of Sweden using variance component estimationErrors of estimated parameters in an adjustment process should be scaled according to the size of the estimated residuals or misclosures. After computing a quasi-geoid (geoid), its biases and tilts, due to existence of systematic errors in the terrestrial data, are removed by fitting a corrective surface to the misclosures of the differences between the GNSS/levelling data and the quasi-geoid (geoid). Variance component estimation can be used to re-scale or calibrate the error of the GNSS/levelling data and the quasi-geoid (geoid) model. This paper uses this method to calibrate the errors of the recent quasi-geoid model, the GNSS and the normal heights of Sweden. Different stochastic models are investigated in this study and based on a 7-parameter corrective surface model and a three-variance component stochastic model, the calibrated error of the quasi-geoid and the normal heights are 6 mm and 5 mm, respectively and the re-scaled error of the GNSS heights is 18 mm.
A mathematical model of the bathymetry-generated external gravitational field
Authors: Tenzer Robert , Vajda Peter , Hamayun Peter 
Published: June 2010

A mathematical model of the bathymetry-generated external gravitational field
The currently available global geopotential models and the global elevation and bathymetry data allow modelling the topography-corrected and bathymetry stripped reference gravity field to a very high spectral resolution (up to degree 2160 of spherical harmonics) using methods for a spherical harmonic analysis and synthesis of the gravity field. When modelling the topography-corrected and crust-density-contrast stripped reference gravity field, additional stripping corrections are applied due to the ice, sediment and other major known density contrasts within the Earth's crust. The currently available data of global crustal density structures have, however, a very low resolution and accuracy. The compilation of the global crust density contrast stripped gravity field is thus limited to a low spectral resolution, typically up to degree 180 of spherical harmonics. In this study we derive the expressions used in forward modelling of the bathymetry-generated gravitational field quantities and the corresponding bathymetric stripping corrections to gravity field quantities by means of the spherical bathymetric (ocean bottom depth) functions. The expressions for the potential and its radial derivative are formulated for the adopted constant (average) ocean saltwater density contrast and for the spherical approximation of the geoid surface. These newly derived expressions are utilized in numerical examples to compute the gravitational potential and attraction generated by the ocean density contrast. The computation is realized globally on a 1 x 1 arc-deg geographical grid at the Earth's surface.