bluuebunny/crossref_metadata_2025 huggingface dataset:
Modelling of JET Diagnostics Using Bayesian Graphical Models
Authors: Svensson J. , Ford O. , McDonald D.C. , Meakins A. , Werner A. , Brix M. , Boboc A. , Beurskens M. , JET EFDA Contributors
Published: March 2011

Modern nuclear fusion experiments utilise a large number of sophisticated plasma diagnostics, which are sensitive to overlapping subsets of the physics parameters of interest. The mapping between the set of all physics pa‐rameters (the plasma ‘state’) and the raw observations of each diagnostic, will depend on the particular physics model used, and will also be inherently probabilistic. Uncertainty enters into the mapping between model parameters and observations through the inability of most models to predict the precise value of an observation, and also through aspects of the diagnostic itself, such as calibrations, instrument functions etc. To optimally utilise observations from multiple diagnostics and properly deal with all aspects of model uncertainties is very difficult with today's data analysis infrastructures. For this work, the Minerva analysis framework [1, 2] has been used, which implements a flexible and general way of modelling and carrying out analysis on this type of interconnected probabilistic systems by modelling of diagnostics, physics models and their dependencies through the use of Bayesian graphical models [3]. To date about 10 diagnostic systems have been modelled in this way at JET, which has already led to a number of new results, including the reconstruction of flux surface topology and q‐profiles without an equilibrium assumption [4], profile inversions including uncertainty in the positions of flux surfaces, first experimental verification of relativistic effects to explain polarimetry measurements [5], and a substantial increase in accuracy of JET electron density and temperature profiles, including improved pedestal resolution, through the joint analysis of three different diagnostic systems [6] (© 2011 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Investigating Transport of Dust Particles in Plasmas
Authors: Bardin S. , Briançon J.‐L. , Brochard F. , Martin V. , Zayachuk Y. , Hugon R. , Bougdira J.
Published: March 2011

An algorithm has been developed, which makes it possible to automatically extract individual trajectories of a large number of particles from fast imaging data, allowing a statistical analysis of particle trajectories under various plasma conditions, a better understanding of their influence on plasma properties, and a better characterization of the plasma itself. In this contribution, we focus on results obtained in a radio‐frequency parallel plate reactor, where a large amount of micron‐sized carbon dust is produced in situ. The use of the rescaled range analysis (R/S analysis) applied to dust particle displacements allows decomposing dust dynamic on different time scales. It is shown that dust displacement is dominated by collisions on short time scales whereas long term behaviour is strongly influenced by large scale fluctuations (© 2011 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
LTE Experimental Validation in a Gas Metal Arc Welding Plasma Column
Authors: Valensi F. , Pellerin S. , Boutaghane A. , Dzierzega K. , Pellerin N. , Briand F.
Published: March 2011

During gas metal arc welding (GMAW), the plasma obtained has a rich composition and some hypothesis are often made for modelling, in particular the local thermodynamical equilibrium (LTE) state of the plasma. It is then important to study its validity domain, as it is also needed for plasma parameters determination.

The plasma was investigated using optical emission spectroscopy. The electron temperature and density were determined from Stark width measurements, independently of the plasma equilibrium state, and compared to the excitation temperature obtained using the Boltzmann plot (BP) method. The welding experiments were made at arc current of 330 A, with pure argon as shielding gases. The LTE is verified in the core region of the plasma, for about one half of the column radius in the arc lower part (© 2011 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Electric Probes in Tokamaks: Experience in Tore Supra
Authors: Gunn J. P. , Pascal J.‐Y. , Saint‐Laurent F. , Gil C.
Published: March 2011

Efforts to provide regular, automatic, and reliable reciprocating probe measurements in the scrape‐off layer of the Tore Supra tokamak are described. Real time feedback on fast magnetic reconstruction is used to control the probe position relative to the last closed flux surface, while analysis of the current‐voltage characteristics is used to adapt the voltage waveform applied to the probe, improving the dynamic range of the measurement. A large probe head is employed to ensure operation in the strongly magnetized plasma regime. Concave collectors embedded in the probe head, so‐called “tunnel probes”, are shown to be immune to sheath expansion effects, providing absolutely calibrated measurements of parallel ion current density (© 2011 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Microparticles as Plasma Diagnostic Tools
Authors: Maurer H.R. , Schneider V. , Wolter M. , Basner R. , Trottenberg T. , Kersten H.
Published: March 2011

An interesting aspect in the research of complex (dusty) plasmas is the experimental study of the interaction of microparticles with the surrounding plasma for diagnostic purposes. Local electric fields can be determined from the behavior of particles in the plasma, i.e. particles may serve as electrostatic probes. From particle trajectories, also the determination of momentum flux in beams is possible, and the particles serve as force probes. Recently, temperature sensitive features of particular phosphors were utilized for measuring the surface temperature of microparticles confined in the sheath of a rf plasma. The experiments were performed under variation of gas pressure and rf power of the process plasma and offer a promising approach for the improvement of process plasmas and the understanding of plasma‐particle interaction (© 2011 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Hydrogeochemical characterization of small coastal wetlands and forests in the Southern Po plain (Northern Italy)
Authors: Marconi V. , Antonellini M. , Balugani E. , Dinelli E.
Published: March 2011

This study is aimed to characterize the shallow groundwater system in the coastal area between the Uniti and Bevano rivers (southern part of the Po plain), where salinization is threatening the coastal ecosystems and posing a major environmental issue for the phreatic water management in the coast. A thin rainwater lens is present at the top of the aquifer in the backshore area and its extent has a seasonal variability. These few centimetres of freshwater represent a thin interface between sea water and the delicate coastal ecosystems, such as those of dunes and wetlands. To have a better understanding of the changes in groundwater chemistry, we performed a seasonal monitoring of the water quality at the top of the aquifer. Effective concentrations of chemicals and actual values of physical‐chemical parameters in the rainwater lens could be measured by means of auger holes. The analysis of the cation‐exchange process in the aquifer was made through the application of the Base Exchange index (BEX index) of Stuyfzand (2008), an indicator of salinization or freshening of waters. The results pointed out that a salinization process is taking place in the largest part of the aquifer. Extension and chemical composition of the rainwater lens are strongly influenced by anthropogenic factors such as drainage and land use. The surface water bodies are all brackish to salty and characterized by anoxic and reducing conditions. At present, only halophytes are present around the dune slacks, which have turned into brackish to hypersaline lakes. Copyright © 2011 John Wiley & Sons, Ltd.
Patch vegetation and water redistribution above and below ground in south‐east Spain
Authors: Archer N. A. L. , Quinton J. N. , Hess T. M.
Published: March 2011

Two sites, one dominated by Anthyllis cytisoides and the other by Retama sphaerocarpa in south‐east Spain were instrumented to measure soil matric potential to a soil depth of 1 m and soil water content to 2·75 m depth within shrubs and grass areas. Soil cores and underground surveys were taken to estimate root length and soil texture, ground cover volume was measured and runoff traps were installed to estimate overland flow in grass and shrub areas. The outcome of the results was summarised as a conceptual model to describe the flow of water within patch vegetation, where the main dominating factor of patch vegetation was found to be the function of shrub canopy/root systems. The results illustrated that not only the dynamics of runoff/runon between grass and shrub areas were significant in redistributing rainfall, but also the morphology of shrub species caused significant differences to the accumulation and movement of water in shrub zones. A comparison of growth and flowering times of grass and shrub species showed that soil water availability for each species differs throughout the year. Such an understanding of water movement within patch vegetation of different species shows that sustainable management practices of semi‐arid areas must take into account not only natural vegetation patterns, but also the function of each plant type. Copyright © 2011 John Wiley & Sons, Ltd.
Splenic CD8α+ dendritic cells undergo rapid programming by cytosolic bacteria and inflammation to induce protective CD8+ T‐cell memory
Authors: Campisi Laura , Soudja Saidi M'Homa , Cazareth Julie , Bassand Delphine , Lazzari Anne , Brau Frédéric , Narni‐Mancinelli Emilie , Glaichenhaus Nicolas , Geissmann Frédéric , Lauvau Grégoire
Published: March 2011

Memory CD8+ T lymphocytes are critical effector cells of the adaptive immune system mediating long‐lived pathogen‐specific protective immunity. Three signals – antigen, costimulation and inflammation – orchestrate optimal CD8+ T‐cell priming and differentiation into effector and memory cells and shape T‐cell functional fate and ability to protect against challenge infections. While among the conventional spleen DCs (cDCs), the CD8α+ but not the CD8α− cDCs most efficiently mediate CD8+ T‐cell priming, it is unclear which subset, irrespective of their capacity to process MHC class I‐associated antigens, is most efficient at inducing naïve CD8+ T‐cell differentiation into pathogen‐specific protective memory cells in vivo. Moreover, the origin of the required signals is still unclear. Using mice infected with the intracellular bacterium Listeria monocytogenes, we show that splenic CD8α+ cDCs become endowed with all functional features to optimally prime protective memory CD8+ T cells in vivo within only a few hours post‐immunization. Such programming requires both cytosolic signals resulting from bacterial invasion of the host cells and extracellular inflammatory mediators. Thus, these data designate these cells as the best candidates to facilitate the development of cell‐based vaccine therapy.
Immobilization‐Free Electrochemical DNA Polymerase Assay
Authors: Luo Xiaoteng , Hsing I‐Ming
Published: March 2011

Based on an immobilization‐free electrochemical DNA detection platform, a novel electrochemical method for detecting and monitoring the activity of DNA polymerase has been developed. The determination of the existence of DNA polymerase is accomplished through the detection of a DNA primer which is elongated along a DNA template under the catalysis of the DNA polymerase. The detection utilizes the competition between the elongated DNA and a ferrocene‐labeled peptide nucleic acid probe (Fc‐PNA) to hybridize with the DNA template in solution. The neutral PNA backbone and the electrostatic repulsion between the negatively charged DNA backbone and the negatively charged electrode surface are then exploited to determine the result of the competition through measurement of the electrochemical signal of Fc. In the presence of the DNA polymerase, the DNA primer is extended to the same length as the DNA template, resulting in stronger hybridization affinity between the two complementary DNA strands, which releases the Fc‐PNA from the Fc‐PNA/template hybrid and allows it to freely diffuse to the negatively charged electrode to produce a significantly enhanced electrochemical signal of Fc. This simple and robust electrochemical DNA polymerase assay does not require any probe immobilization steps and could potentially benefit drug development research, as well as on‐site pathogen monitoring applications.
Pharmaceutical modulation of diffusion potentials at aqueous–aqueous boundaries under laminar flow conditions
Authors: Collins Courtney J. , Strutwolf Jörg , Arrigan Damien W. M.
Published: March 2011

In this work, the modulation of the diffusion potential formed at the microfluidic aqueous–aqueous boundary by a pharmaceutical substance is presented. Co‐flowing aqueous streams in a microchannel were used to form the stable boundary between the streams. Measurement of the open circuit potential between two silver/silver chloride electrodes enabled the diffusion potential at the boundary to be determined, which is concentration dependent. Experimental results for protonated propranolol as well as tetrapropylammonium are presented. This concept may be useful as a strategy for the detection of drug substances.
A multi‐functional electrochemical sensing system using microfluidic technology for the detection of urea and creatinine
Authors: Huang Chao‐June , Lin Jiun‐Lin , Chen Ping‐Hong , Syu Mei‐Jywan , Lee Gwo‐Bin
Published: March 2011

This study presents a new microfluidic system capable of precise measurements of two important biomarkers, urea and creatinine, automatically. In clinical applications, high levels of these two biomarkers are early indicators of nephropathy or renal failure and should be monitored on a regular basis. The microfluidic system is composed of a microfluidic chip, a control circuit system, a compressed air source and several electromagnetic valves to form a handheld system. The microfluidic chip is fabricated by using micro‐electromechanical systems and microfluidic techniques comprising electrochemical sensor arrays and polydimethylsiloxane‐based microfluidic structures such as micropumps/micromixers, normally closed valves and microchannels. The microfluidic system performs a variety of critical processes including sample pretreatment, mixing, transportation and detection on a single chip. The experimental results show that the entire procedure takes approximately 40 min, which is much faster than the traditional method (more than 6 h). Furthermore, the total sample volume consumed in each operation is only 0.1 mL, which is significantly less than that required in a large system (5 mL). The developed automatic microfluidic system may provide a powerful platform for further clinical applications.
A modified electrode for the electrochemical detection of biogenic amines and their amino acid precursors separated by microchip capillary electrophoresis
Authors: Dossi Nicolò , Toniolo Rosanna , Pizzariello Andrea , Susmel Sabina , Bontempelli Gino
Published: March 2011

The use of a mixed‐valent ruthenium oxide/hexacyanoruthenate polymeric film electrochemically deposited onto glassy carbon electrodes is proposed here for the detection of biogenic amines and their amino acid precursors, following their separation by microchip capillary electrophoresis. The ability of this ruthenium coating to electrocatalyze the oxidation of aliphatic and heterocyclic amines, as well as their amino acid precursors, was checked by using ethanolamine, tryptamine and tryptophane as prototype compounds and adopting a 25 mM sulphuric acid as the electrolyte in the detection cell, where a constant potential of 1.05 V versus Ag/AgCl, 3 M KCl was applied to the modified working electrode. Optimization of parameters affecting both detection and separation steps led to satisfactory separations when performed by using a 20 mM phosphate running buffer (pH 2.5) and applying a high voltage of 2.5 kV both in the separation and in the electrokinetic injection (duration 4 s). The recorded peaks were characterized by good repeatability (RSD≤3.6%), high sensitivity and a wide linear range. Detection limits of 23 μM (1.4 mg/L), 27 μM (4.3 mg/L) and 34 μM (6.8 mg/L) were inferred for ethanolamine, tryptamine and tryptophane, respectively. The approach proposed here was also applied for the analysis of some double malt dark beers spiked with a controlled amount of the analytes considered.
Noninvasive imaging of oral neoplasia with a high‐resolution fiber‐optic microendoscope
Authors: Muldoon Timothy J. , Roblyer Darren , Williams Michelle D. , Stepanek Vanda M.T. , Richards–Kortum Rebecca , Gillenwater Ann M.
Published: March 2011

Background

The purpose of this study was to evaluate the ability of high‐resolution microendoscopy to image and quantify changes in cellular and architectural features seen in early oral neoplasia in vivo.

Methods

A high‐resolution microendoscope (HRME) was used to image intact, resected oral squamous carcinoma specimens. HRME images were reviewed and classified as non‐neoplastic or neoplastic by expert clinicians. An algorithm based on quantitative morphologic features was also used to classify each image. Results were compared to the histopathologic diagnosis.

Results

HRME images were obtained from 141 sites in resected specimens from 13 patients. Subjective image interpretation yielded sensitivity and specificity of 85% to 90% and 80% to 85%, respectively, whereas the objective classification algorithm achieved sensitivity and specificity of 81% and 77%, respectively.

Conclusion

High‐resolution microendoscopy of intact oral mucosa can provide images with sufficient detail to classify oral lesions by both subjective image interpretation and objective image analysis. © 2011 Wiley Periodicals, Inc. Head Neck, 2012
Global‐scale river routing—an efficient time‐delay algorithm based on HydroSHEDS high‐resolution hydrography
Authors: Gong L. , Halldin S. , Xu C.‐Y.
Published: March 2011

Coupling of global hydrologic and atmospheric models is difficult because of the highly nonlinear hydrological processes to be integrated at large scales. Aggregation of high‐resolution data into low‐resolution spatial distribution functions is one way to preserve information and account for the nonlinearity. We used HydroSHEDS, presently the most highly resolved (3″) global hydrography available, to provide accurate control on global river routing through a computationally efficient algorithm. The high resolution of HydroSHEDS allowed discrimination of river‐channel pixels, and time‐delay distributions were calculated for all such pixels. The distributions were aggregated into network‐response functions (NRFs) for each low‐resolution cell using an algorithm originally developed for the 1‐km‐resolution HYDRO1k hydrography. The large size of HydroSHEDS required a modification in algorithm to maintain computational efficiency. The new algorithm was tested with a high‐quality local and a more uncertain global weather dataset to identify whether improved routing would provide a gain when weather data quality was limiting. The routing was coupled to the WASMOD‐M runoff‐generation model to evaluate discharge from the Dongjiang River and the Willamette River basins. The HydroSHEDS‐based routing, compared with the HYDRO1k‐based routing, provided a small gain in model efficiency, for local and global weather data and for both test basins. The HydroSHEDS‐based routing, contrary to the HYDRO1k‐based routing, provided physically realistic wave velocities. The most stable runoff‐generation parameter values were achieved when HydroSHEDS was used to derive the NRFs. Routing was computed in two steps: first, a preparatory calculation which was a one‐time effort and second, the routing during each simulation. The computational efficiency was four to five orders of magnitude better for the simulation step than that for the preparatory step. Copyright © 2010 John Wiley & Sons, Ltd.
Circulating estrogens and progesterone during primiparous pregnancies and risk of maternal breast cancer
Authors: Lukanova Annekatrin , Surcel Helja‐Marja , Lundin Eva , Kaasila Marjo , Lakso Hans‐Ake , Schock Helena , Husing Anika , Kaaks Rudolf , Koskela Pentti , Grankvist Kjell , Pukkala Eero , Zeleniuch‐Jacquotte Anne , Lehtinen Matti , Toniolo Paolo
Published: March 2011

Pregnancy reduces maternal risk of breast cancer in the long term, but the biological determinants of the protection are unknown. Animal experiments suggest that estrogens and progesterone could be involved, but direct human evidence is scant. A case‐control study (536 cases and 1,049 controls) was nested within the Finnish Maternity Cohort. Eligible were primiparous women who delivered at term a singleton offspring before age 40. For each case, two individually matched controls by age (±6 months) and date of sampling (±3 months) were selected. Estradiol, estrone and progesterone in first‐trimester serum were measured by high‐performance liquid chromatography tandem mass spectrometry and sex‐hormone binding globulin (SHBG) by immunoassay. Odds ratios (OR) and 95% confidence intervals (CI) were estimated through conditional logistic regression. In the whole study population there was no association of breast cancer with any of the studied hormones. In analyses stratified by age at diagnosis, however, estradiol concentrations were positively associated with risk of breast cancer before age 40 (upper quartile OR, 1.81; CI, 1.08–3.06), but inversely associated with risk in women who were diagnosed ≥age 40 (upper quartile OR, 0.64; CI, 0.40–1.04), pinteraction 0.004. Risk estimates for estrone mirrored those for estradiol but were less pronounced. Progesterone was not associated with risk of subsequent breast cancer. Our results provide initial evidence that concentrations of estrogens during the early parts of a primiparous pregnancy are associated with maternal risk of breast cancer and suggest that the effect may differ for tumors diagnosed before and after age 40.
Prospective study on the role of glucose metabolism in breast cancer occurrence
Authors: Sieri Sabina , Muti Paola , Claudia Agnoli , Berrino Franco , Pala Valeria , Grioni Sara , Abagnato Carlo Alberto , Blandino Giovanni , Contiero Paolo , Schunemann Holger J. , Krogh Vittorio
Published: March 2011

High circulating glucose, insulin resistance and obesity appear to be associated with increased risk of breast cancer (BC). We sought further insight into the relation of these variables to BC. We assessed associations of BC risk with serum fasting glucose, insulin, homeostasis model assessment‐insulin resistance (HOMA‐IR) index and sex‐binding hormone globulin (SHBG) in women recruited to the ORDET cohort who gave blood samples in 1987–1992. After a median 13.5 years of follow‐up, 356 women developed BC. Four matched controls per case were selected by incidence density sampling, and rate ratios (RR) were estimated by conditional logistic regression. Women in the highest glucose quartile had a significantly greater risk of BC than those in the lowest glucose quartile (RR 1.63; 95% CI: 1.14–2.32; p for trend of 0.003). The association was significant in pre and post menopausal women separately and in women diagnosed after 55 years. Women in the highest HOMA‐IR quartile had higher BC risk than the lowest quartile (RR 1.44; 95% CI: 1.03–2.02). Significantly increased BC risk in women diagnosed after 55 years was also present in the highest HOMA‐IR quartile; in the same group decreased BC risk was significantly associated with high SHBG. The results of this study add to the existing epidemiological evidence that hyperglycemia and insulin resistance increase BC risk.
Heteroclitic serological response in esophageal and prostate cancer patients after NY‐ESO‐1 protein vaccination
Authors: Kawada Junji , Wada Hisashi , Isobe Midori , Gnjatic Sacha , Nishikawa Hiroyoshi , Jungbluth Achim A. , Okazaki Nami , Uenaka Akiko , Nakamura Yurika , Fujiwara Shinichi , Mizuno Naoaki , Saika Takashi , Ritter Erika , Yamasaki Makoto , Miyata Hiroshi , Ritter Gerd , Murphy Roger , Venhaus Ralph , Pan Linda , Old Lloyd J. , Doki Yuichiro , Nakayama Eiichi
Published: March 2011

NY‐ESO‐1 is a prototypic cancer/testis antigen. In a recent phase I clinical trial, we vaccinated 13 patients bearing NY‐ESO‐1‐expressing tumors with a complex of cholesterol‐bearing hydrophobized pullulan (CHP) and NY‐ESO‐1 protein (CHP‐NY‐ESO‐1) and showed efficient induction of NY‐ESO‐1 antibody, and CD4 and CD8 T cell responses using peripheral blood from the patients. In our study, we analyzed heteroclitic serological responses in those patients after vaccination. Serological response against 11 tumor antigens including MAGE‐A1, MAGE‐A3, MAGE‐A4, CT7/MAGEC1, CT10/MAGEC2, CT45, CT46/HORMAD1, SOX2, SSX2, XAGE1B and p53 was examined by enzyme‐linked immunosorbent assay (ELISA) using sera from ten vaccinated patients. Expression of tumor antigens was determined by reverse transcription‐polymerase chain reaction or immunohistochemistry. Eight of nine patients who showed antibody responses against NY‐ESO‐1 also showed an antibody response against at least 1 of these 11 tumor antigens after vaccination. In one patient, seven tumor antigens were recognized. Specificity analysis of the antibody response by ELISA using control recombinant proteins and synthetic peptides and by Western blot showed that the response was not against His6‐tag and/or bacterial products included in a preparation of CHP‐NY‐ESO‐1 used for vaccination. Thus, heteroclitic serological responses appear to be indicative of the overall immune response against the tumor, and their analysis could be useful for immune monitoring in cancer vaccine.
An intact retinoblastoma protein‐binding site in Merkel cell polyomavirus large T antigen is required for promoting growth of Merkel cell carcinoma cells
Authors: Houben Roland , Adam Christian , Baeurle Anne , Hesbacher Sonja , Grimm Johannes , Angermeyer Sabrina , Henzel Katharina , Hauser Stefanie , Elling Roland , Bröcker Eva‐B. , Gaubatz Stefan , Becker Jürgen C. , Schrama David
Published: March 2011

Merkel cell carcinoma (MCC) is a highly aggressive skin cancer that frequently harbours Merkel cell polyomavirus (MCV) DNA integrated in the genome of the tumor cells. In our study, we elaborate our recent finding that MCV‐positive MCC cell lines require the expression of the viral T antigens (TA). Indeed, in a xeno‐transplantation model, we prove that TA expression is essential also in an in vivo situation, as knock down of TA leads to tumor regression. Moreover, rescuing TA short hairpin RNA (shRNA)‐treated MCV‐positive MCC cells by ectopic expression of shRNA‐insensitive TAs clearly demonstrates that the observed effect is caused by TA knockdown. Notably, introduction of a mutation in the LTA protein interfering with LTA binding to the retinoblastoma protein (RB) ablated this rescue. The importance of this interaction was further confirmed as LTA‐specific knockdown leads to explicit cell growth inhibition. In summary, the presented data demonstrate that established MCV‐positive MCC tumors critically depend on TA expression, in particular the LTA and RB interaction, for sustained tumor growth. Consequently, interference with LTA/RB interaction appears as promising strategy to treat MCC.
Epigenetic markers for chemosensitivity and chemoresistance in pancreatic cancer—A review
Authors: Dhayat Sameer , Mardin Wolf Arif , Mees Soeren Torge , Haier Joerg
Published: March 2011

Adjuvant first‐line gemcitabine monochemotherapy presents a standard treatment for patients with advanced pancreatic adenocarcinoma and improves overall survival in chemosensitive patients. Nonetheless, 6‐month progression‐free survival remains below 15%, despite interdisciplinary approaches. The success of gemcitabine treatment is disappointing and—in the absence of reliable tumor markers—challenging to quantify. Epigenetic alterations have been recently identified to take on important roles in cancer development and possibly cancer treatment. In this context, microRNAs are becoming increasingly acknowledged as useful biomarkers for classifying cancers and providing information on their chemo‐ and radiosensitivity. This review illustrates the potential of genetic and epigenetic markers in the prediction of chemosensitivity in pancreatic cancer patients and in the monitoring of their response rates to adjuvant therapy.
SPATIAL MAPPING OF AGRICULTURAL WATER PRODUCTIVITY USING THE SWAT MODEL IN UPPER BHIMA CATCHMENT, INDIA
Authors: Garg Kaushal K. , Bharati Luna , Gaur Anju , George Biju , Acharya Sreedhar , Jella Kiran , Narasimhan B.
Published: March 2011

The Upper Bhima River Basin is facing both episodic and chronic water shortages due to intensive irrigation development. The main objective of this study was to characterize the hydrologic processes of the Upper Bhima River Basin and assess crop water productivity using the distributed hydrologic model, SWAT. Rainfall within the basin varies from 450 to 5000 mm in a period of 3–4 months. The basin has an average rainfall of 711 mm (32 400 Mm3 (million cubic metres)) in a normal year, of which 12.8% (4150 Mm3) and 21% (6800 Mm3) are captured by the reservoirs and groundwater reserves, respectively, 7% (2260 Mm3) exported as runoff out of the basin and the rest (63%) used in evapotranspiration. Agricultural water productivity for sugarcane, sorghum and millet were estimated as 2.90, 0.51 and 0.30 kg m−3, respectively, which were significantly lower than the potential and global maximum in the basin and warrant further improvement. Various scenarios involving different cropping patterns were tested with the goal of increasing economic water productivity values in the Ujjani Irrigation Scheme. Analysis suggests that maximization of the area by provision of supplemental irrigation to rainfed areas as well as better on‐farm water management practices can provide opportunities for improving water productivity. Copyright © 2011 John Wiley & Sons, Ltd.
Evaluation and identification of reliable reference genes for pharmacogenomics, toxicogenomics, and small RNA expression analysis
Authors: Chen Dongliang , Pan Xiaoping , Xiao Peng , Farwell Mary A. , Zhang Baohong
Published: March 2011

Pharmacogenomics, toxicogenomics, and small RNA expression analysis are three of the most active research topics in the biological, biomedical, pharmaceutical, and toxicological fields. All of these studies are based on gene expression analysis, which requires reference genes to reduce the variations derived from different amounts of starting materials and different efficiencies of RNA extraction and cDNA synthesis. Thus, accurate normalization to one or several constitutively expressed reference genes is a prerequisite to valid gene expression studies. Although selection of reliable reference genes has been conducted in previous studies in several animals and plants, no research has been focused on pharmacological targets, and very few studies have had a toxicological context. More interestingly, no studies have been performed to identify reference genes for small RNA analysis although small RNA, particularly microRNA (miRNA)‐related research is currently one of the fastest‐moving topics. In this study, using MCF‐7 breast cancer cells as a model, we employed quantitative real‐time PCR (qRT‐PCR), one of the most reliable methods for gene expression analysis in many research fields, to evaluate and to determine the most reliable reference genes for pharmacogenomics and toxicogenomics studies as well as for small RNA expression analysis. We tested the transcriptional expression of five protein‐coding genes as well as five non‐coding genes in MCF‐7 cells treated with five different pharmaceuticals or toxicants [paclitaxel (PTX), gossypol (GOS), methyl jasmonate (JAS), L‐nicotine (NIC), and melamine (mela)] and analyzed the stability of the selected reference genes by four different methods: geNorm, NormFinder, BestKeeper, and the comparative ΔCt method. According to our analysis, a protein‐coding gene, hTBCA and four non‐coding genes, hRNU44, hRNU48, hU6, and hRNU47, appear to be the most reliable reference genes for the five chemical treatments. Similar results were also obtained in dose‐response and time‐course assays with gossypol (GOS) treatment. Our results demonstrated that traditionally used reference genes, such as 18s RNA, β‐actin, and GAPDH, are not reliable reference genes for pharmacogenomics and toxicogenomics studies. In contrast, hTBCA and small RNAs are more stable during drug treatment, and they are better reference genes for pharmacogenomics and toxicogenomics studies. To widely use these genes as reference genes, these results should be corroborated by studies with other human cell lines and additional drugs classes and hormonal treatments. J. Cell. Physiol. 226: 2469–2477, 2011. © 2011 Wiley‐Liss, Inc.
Protective effects of adiponectin against renal ischemia‐reperfusion injury via prostacyclin‐PPARα‐Heme oxygenase‐1 signaling pathway
Authors: Cheng Ching‐Feng , Lian Wei‐Shiung , Chen Sung‐Ho , Lai Pei‐Fen , Li Hsiao‐Fen , Lan Yi‐Fan , Cheng Winston Teng‐Kuei , Lin Heng
Published: March 2011

Adiponectin (APN), a circulating adipose‐derived hormone that regulates inflammation and energy metabolism, has beneficial effects on the cardiovascular disorders. Serum APN levels are lower in patients with coronary artery disease and higher in patients with chronic kidney disease. However, the precise role of APN in acute reno‐vascular disease is not clear. Results of the present study show that serum APN concentration decreased after renal ischemia reperfusion (I/R) injury in mice. In addition, I/R‐induced renal dysfunction (elevated serum creatinine and urea levels), inflammation (number of infiltrating neutrophils, myeloperoxidase activity), and apoptotic responses (apoptotic cell number and caspase‐3 activation) were attenuated in APN‐treated compared to control mice. Molecular and biochemical analysis revealed that APN up‐regulates heme oxygenase‐1 (HO‐1) via peroxisome‐proliferator‐activated‐receptor‐α (PPARα) dependent pathway which is mediated through the enhancement of COX‐2 and 6‐keto PGF1α expression. Chromatin immune‐precipitation assay demonstrated that APN increases the binding activity of PPARα to PPRE region of HO‐1 promoter. Furthermore, APN induced HO‐1 expression was only found in wild‐type but not in PPARα gene deleted mice. This provides in vivo evidence that APN mediated HO‐1 expression depends on PPARα regulation. In conclusion, our results provide a novel APN mediated prostacyclin‐PPARα‐HO‐1 signaling pathway in protecting renal I/R injury. J. Cell. Physiol. 227: 239–249, 2012. © 2011 Wiley Periodicals, Inc.
Interaction of endocannabinoid system and steroid Hormones in the control of colon cancer cell growth
Authors: Proto Maria C. , Gazzerro Patrizia , Di Croce Luciano , Santoro Antonietta , Malfitano Anna M. , Pisanti Simona , Laezza Chiara , Bifulco Maurizio
Published: March 2011

Increasing evidence suggest the role of the cannabinoid receptors (CBs) in the control of cell survival or death and signaling pathways involved in tumor progression. Cancer cell lines are characterized by a subtle modulation of CB levels which produces a modified responsiveness to specific ligands, but the molecular mechanisms underlying these events are poorly and partially understood. We previously provided evidence that the endocannabinoid (EC) anandamide (AEA) exerts anti‐proliferative effect likely by modulation of the expression of genes involved in the cellular fate. In this study we focused on the role of the CB1 receptor, ECs, and steroids in the mechanisms involved in colorectal cancer (CRC) cell growth inhibition in vitro. We demonstrated that, in DLD1 and SW620 cells, 17β‐estradiol induced a specific and strong up‐regulation of the CB1 receptor by triggering activation of the CB1 promoting region, localized at the exon 1 of the CNR1 gene. Moreover, treatment of DLD1 and SW620 cells with Met‐F‐AEA, a stable AEA‐analogous, or URB597, a selective inhibitor of FAAH, induced up‐regulation of CB1 expression by co‐localization of PPARγ and RXRα at the promoting region. Finally, increased availability of AEA, of both exogenous and endogenous sources, induced the expression of estrogen receptor‐beta in both cell lines. Our results partially elucidated the role of EC system in the molecular mechanisms enrolled by steroids in the inhibition of colon cancer cell growth and strongly suggested that targeting the EC system could represent a promising tool to improve the efficacy of CRC treatments. J. Cell. Physiol. 227: 250–258, 2012. © 2011 Wiley Periodicals, Inc.
MicroRNAs: Allies or Foes in erythropoiesis?
Authors: Byon John C.H. , Papayannopoulou Thalia
Published: March 2011

MicroRNAs are small non‐coding RNAs that negatively regulate gene expression through mRNA degradation or translational repression. It is becoming increasingly recognized that miRNAs play central roles in almost all cellular processes, and especially during development. The function of miRNAs in hematopoiesis, including erythropoiesis, is beginning to be elucidated. In this review, we will focus on what is known about miRNA function in various aspects of erythropoiesis and red cell physiology. J. Cell. Physiol. 227: 7–13, 2012. © 2011 Wiley Periodicals, Inc.
Gremlin1 is required for skeletal development and postnatal skeletal homeostasis
Authors: Canalis Ernesto , Parker Kristen , Zanotti Stefano
Published: March 2011

Gremlin is an antagonist of bone morphogenetic proteins, and its overexpression causes suppressed osteoblastogenesis and osteopenia. Inactivation of Grem1 results in severe developmental defects, but the consequences of the global inactivation of Grem1 on the postnatal skeleton are not known. To study the function of gremlin, Grem1 was inactivated by homologous recombination, and mice were maintained in a C57BL/6/FVB mixed genetic background due to embryonic and neonatal lethality in the uniform C57BL/6 background. Grem1 null mice exhibited developmental skeletal abnormalities, leading to incomplete formation of metatarsal bones and of fore limbs and hind limbs. Grem1 null mice exhibited decreased weight and body fat and shortened femoral length. Bone histomorphometric and microarchitectural analyses of distal femurs revealed decreased bone volume and increased bone formation in 1‐month‐old Grem1 null mice. Trabecular femoral bone volume was restored in older Grem1 null female mice, and to a lesser extent in male mice. Vertebral microarchitecture confirmed the osteopenia observed in 1‐month‐old Grem1 null mice and demonstrated recovery of trabecular bone in older female, but not in older male Grem1 null mice, which exhibited persistent vertebral osteopenia. In conclusion, Grem1 is not only necessary for skeletal development, but also for postnatal skeletal homeostasis; its inactivation causes osteopenia, which is partially reversed in a spatial, temporal, and sex‐dependent manner due to an increase in bone formation. J. Cell. Physiol. 227: 269–277, 2012. © 2011 Wiley Periodicals, Inc.
The science of stem cell biobanking: Investing in the future
Authors: Diaferia Giuseppe R. , Cardano Marina , Cattaneo Monica , Spinelli Chiara C. , Dessì Sara S. , DeBlasio Pasquale , Biunno Ida
Published: March 2011

The use of human stem cells in biomedical research projects is increasing steadily and the number of cells that are being derived develops at a remarkable pace. However, stem cells around the world are vastly different in their provenance, programming, and potentials. Furthermore, knowledge on the actual number of cell types, their derivation, availability, and characteristics is rather sparse. Usually, “colleague‐supply” avenues constantly furnish cells to laboratories around the world without ensuring their correct identity, characterization, and quality. These parameters are critical if the cells will be eventually used in toxicology studies and drug discovery. Here, we outline some basic principles in establishing a stem cell‐specific bank. J. Cell. Physiol. 227: 14–19, 2012. © 2011 Wiley Periodicals, Inc.
Genetic variation of the hemagglutinin of avian influenza virus H9N2
Authors: Song Xiao‐feng , Han Ping , Chen Yi‐Ping Phoebe
Published: March 2011

Avian influenza virus H9N2 has become the dominant subtype of influenza which is endemic in poultry. The hemagglutinin, one of eight protein‐coding genes, plays an important role during the early stage of infection. The adaptive evolution and the positively selected sites of the HA (the glycoprotein molecule) of H9N2 subtype viruses were investigated. Investigating 68 hemagglutinin H9N2 avian influenza virus isolates in China and phylogenetic analysis, it was necessary that these isolates were distributed geographically from 1994, and were all derived from the Eurasian lineage. H9N2 avian influenza virus isolates from domestic poultry in China were distinct phylogenetically from those isolated in Hong Kong, including viruses which had infected humans. Seven amino acid substitutions (2T, 3T, 14T, 165D, 197A, 233Q, 380R) were identified in the HA possibly due to positive selection pressure. Apart from the 380R site, the other positively selected sites detected were all located near the receptor‐binding site of the HA1 strain. Based on epidemiological and phylogenetics analysis, the H9N2 epidemic in China was divided into three groups: the 1994–1997 group, the 1998–1999 group, and the 2000–2007 group. By investigating these three groups using the maximum likelihood estimation method, there were more positive selective sites in the 1994–1997 and 1998–1999 epidemic group than the 2000–2007 groups. This indicates that those detected selected sites are changed during different epidemic periods and the evolution of H9N2 is currently slow. The antigenic determinant or other key functional amino acid sites should be of concern because their adjacent sites have been under positive selection pressure. The results provide further evidence that the pathogenic changes in the H9N2 subtype are due mainly to re‐assortment with other highly pathogenic avian influenza viruses. J. Med. Virol. 83:838–846, 2011. © 2011 Wiley‐Liss, Inc.
Chitosan as an adjuvant for poliovaccine
Authors: Ghendon Y. , Markushin S. , Akopova I. , Koptiaeva I. , Krivtsov G.
Published: March 2011

The use of inactivated poliomyelitis vaccine is very important for eradicating poliomyelitis. However, this vaccine is not available readily in underdeveloped countries due to the high cost. Adjuvants can improve the immunogenicity of a vaccine and reduce the antigen dose required for vaccination, thus lowering the cost of the vaccine. Chitosan glutamate solution and a chitosan sulfate micro/nanoparticle suspension were tested as adjuvants for Imovax‐inactivated poliovaccine and for inactivated monovalent poliovirus type 1, 2, and 3 vaccines obtained by inactivation of the attenuated Sabin poliovirus strains. Inactivated vaccines admixed with either chitosan glutamate or chitosan sulfate micro/nanoparticles and administered to mice showed significantly enhanced immunogenicity to poliovirus type 1, 2, and 3 strains compared to the respective vaccines administered without chitosan. Chitosan preparations increased the immunogenicity of 1:2 and 1:4 diluted inactivated Sabin strain preparations in mice 8‐ to 16‐fold, so that the neutralizing antibody titers after vaccination with adjuvanted diluted vaccine were equal to those obtained after vaccination with undiluted vaccine administered without chitosan. Neutralizing antibodies could be detected in sera of rats vaccinated with undiluted, 1:10, and 1:100 diluted Imovax vaccine admixed with chitosan sulfate micro/nanoparticles, although in the control group, vaccination only with the undiluted vaccine resulted in antibody production. These results show that the chitosan glutamate solution and chitosan sulfate micro/nanoparticle suspension can significantly improve the immunogenicity of various poliovaccines, and reduce the effective antigen dose. J. Med. Virol. 83:847–852, 2011. © 2011 Wiley‐Liss, Inc.
Characterization of human immunodeficiency virus (HIV1C) variants in peripheral blood mononuclear cells and spermatozoa
Authors: Jadhav Shivaji K. , Velhal Shilpa M. , Deshpande Alaka , Maitra Anurupa , Chinnaraj Saravanan , Bandivdekar Atmaram H.
Published: March 2011

The presence of distinct viral variants in different cells and secretions of the same person influences the transmission of HIV as well as the response to the host defense and to therapy. Sperm‐associated virus is also a risk factor for sexual transmission of HIV. Characterization of the C2–V3 region of HIV1C env gene by the Heteroduplex Mobility Assay (HMA) and sequencing demonstrated the presence of distinct variants in the peripheral blood mononuclear cells (PBMCs) and the sperm of the same individual (n = 6). The translated amino acid sequences of HIV variants in the PBMCs of all the study participants (n = 12) and spermatozoa of the six participants characterized showed the presence of distinct variants with different numbers of N‐linked glycosylation (NLG) sites. Infectivity of PBMCs of these persons by co‐culture with PBMCs from healthy individuals as detected by the p24 levels in the culture supernatant did not show a correlation with the blood plasma viral load. Interestingly, the infectivity of the sperm samples from four of the five individuals showed positive correlation with the viral load in seminal plasma. The study suggests the presence of distinct viral variants in the sperm and PBMCs of the same person with differential infectivity, and the NLG sites may be associated with the affinity of HIV to receptor/co‐receptor usages as well as affinity toward neutralizing antibodies which may influence the risk of sperm associated virus in sexual transmission of HIV and transmit the virus further to distal cells. J. Med. Virol. 83:760–767, 2011. © 2011 Wiley‐Liss, Inc.
Efficacy of interferon‐based antiviral therapy in patients with chronic hepatitis C infected with genotype 5: A meta‐analysis of two large prospective clinical trials
Authors: D'Heygere François , George Christophe , Van Vlierberghe Hans , Decaestecker Jochen , Nakad Antoine , Adler Michael , Delwaide Jean , Laureys Annick , Nevens Frederik
Published: March 2011

The characteristics and response rate to pegylated interferon and ribavirin (PEG‐INF + RBV) of patients with chronic hepatitis C infected with genotype 5 are poorly documented. A meta‐analysis of two large phase III/IV prospective randomized clinical trials conducted in Belgium in patients with chronic hepatitis C (n = 1,073 patients) was performed in order to compare the response to antiviral therapy of hepatitis C virus (HCV) genotype 5 with that of other HCV genotypes. A subset of HCV‐1 infected patients selected from within the study database were selected to match the HCV‐5 sample for known prognostic factors. In Belgium HCV‐5 is responsible for a significant minority of cases of chronic hepatitis C CHC (4.5%) and is characterized by a more advanced age (58.4 years), a high frequency of cirrhosis (27.7%), a specific mode of HCV acquisition, and a particular geographic origin (66.7% of patients from West Flanders). The primary comparative analysis showed that response to treatment with PEG‐INF + RBV of HCV‐5 is similar to HCV‐1 and lower compared to HCV‐2/3. The analysis of the matched patient subgroup demonstrates that the HCV‐5 “intrinsic sensitivity” to PEG‐IFN + RBV therapy is identical to HCV‐1, with a sustained virological response of 55% in both groups. In contrast to previous publications, this meta‐analysis suggests that HCV‐5 response to treatment is closer to HCV‐1 than to HCV‐2/3 and suggests that in Belgium HCV‐5 infection should be treated with the same antiviral regimen as HCV‐1. J. Med. Virol. 83:815–819, 2011. © 2011 Wiley‐Liss, Inc.