bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cell behavior observation and gene expression analysis of melanoma associated with stromal fibroblasts in a three‐dimensional magnetic cell culture array
Authors: Okochi Mina , Matsumura Taku , Yamamoto and Shuhei , Nakayama Eiichi , Jimbow Kowichi , Honda Hiroyuki 
Published: October 2012

AbstractA three‐dimensional (3D) multicellular tumor spheroid culture array has been fabricated using a magnetic force‐based cell patterning method, analyzing the effect of stromal fibroblast on the invasive capacity of melanoma. Formation of spheroids was observed when array‐like multicellular patterns of melanoma were developed using a pin‐holder device made of magnetic soft iron and an external magnet, which enables the assembly of the magnetically labeled cells on the collagen gel‐coated surface as array‐like cell patterns. The interaction of fibroblast on the invasion of melanoma was investigated using three types of cell interaction models: (i) fibroblasts were magnetically labeled and patterned together in array with melanoma spheroids (direct‐interaction model), (ii) fibroblasts coexisting in the upper collagen gel (indirect‐interaction model) of melanoma spheroids, and (iii) fibroblast‐sheets coexisting under melanoma spheroids (fibroblast‐sheet model). The fibroblast‐sheet model has largely increased the invasive capacity of melanoma, and the promotion of adhesion, migration, and invasion were also observed. In the fibroblast‐sheet model, the expression of IL‐8 and MMP‐2 increased by 24‐fold and 2‐fold, respectively, in real time RT‐PCR compared to the absence of fibroblasts. The results presented in this study demonstrate the importance of fibroblast interaction to invasive capacity of melanoma in the 3D in vitro bioengineered tumor microenvironment. © 2012 American Institute of Chemical Engineers Biotechnol. Prog., 2013
Matrix effects during monitoring of antibody and host cell proteins using attenuated total reflection spectroscopy
Authors: Capito Florian , Skudas Romas , Stanislawski Bernd , Kolmar Harald 
Published: October 2012

AbstractProduction of recombinant proteins, e.g. antibodies, requires constant real‐time monitoring to optimize yield and quality attributes and to respond to changing production conditions, such as host cell protein (HCP) titers. To date, this monitoring of mammalian cell culture‐based processes is done using laborious and time consuming enzyme‐linked immunosorbent assays (ELISA), two‐dimensional sodium dodecylsulphate polyacrylamide gel electrophoresis, and chromatography‐based systems. Measurements are usually performed off‐line, requiring regular sample withdrawal associated with increased contamination risk. As information is obtained retrospectively, the reaction time to adapt to process changes is too long, leading to lower yield and higher costs. To address the resulting demand for continuous online‐monitoring systems, we present a feasibility study using attenuated total reflection spectroscopy (ATR) to monitor mAb and HCP levels of NS0 cell culture in situ, taking matrix effects into account. Fifty‐six NS0 cell culture samples were treated with polyelectrolytes for semi‐selective protein precipitation. Additionally, part of the samples was subjected to filtration prior to analysis, to change the background matrix and evaluate effects on chemometric quantification models. General models to quantify HCP and mAb in both filtered and unfiltered matrix showed lower prediction accuracy compared to models designed for a specific matrix. HCP quantification in the range of 2,000–55,000 ng mL−1 using specific models was accurate for most samples, with results within the accepted limit of an ELISA assay. In contrast, mAb prediction was less accurate, predicting mAb in the range of 0.2–1.7 g L−1. As some samples deviated substantially from reference values, further investigations elucidating the suitability of ATR for monitoring are required. © 2012 American Institute of Chemical Engineers Biotechnol. Prog., 2013
Biohydrogen production by dark fermentation of glycerol using Enterobacter and Citrobacter Sp
Authors: Maru Biniam T. , Constanti Magda , Stchigel Alberto M. , Medina Francesc , Sueiras Jesus E. 
Published: October 2012

AbstractGlycerol is an attractive substrate for biohydrogen production because, in theory, it can produce 3 mol of hydrogen per mol of glycerol. Moreover, glycerol is produced in substantial amounts as a byproduct of producing biodiesel, the demand for which has increased in recent years. Therefore, hydrogen production from glycerol was studied by dark fermentation using three strains of bacteria: namely, Enterobacter spH1, Enterobacter spH2, and Citrobacter freundii H3 and a mixture thereof (1:1:1). It was found that, when an initial concentration of 20 g/L of glycerol was used, all three strains and their mixture produced substantial amounts of hydrogen ranging from 2400 to 3500 mL/L, being highest for C. freundii H3 (3547 mL/L) and Enterobacter spH1 (3506 mL/L). The main nongaseous fermentation products were ethanol and acetate, albeit in different ratios. For Enterobacter spH1, Enterobacter spH2, C. freundii H3, and the mixture (1:1:1), the ethanol yields (in mol EtOH/mol glycerol consumed) were 0.96, 0.67, 0.31, and 0.66, respectively. Compared to the individual strains, the mixture (1:1:1) did not show a significantly higher hydrogen level, indicating that there was no synergistic effect. Enterobacter spH1 was selected for further investigation because of its higher yield of hydrogen and ethanol. © 2012 American Institute of Chemical Engineers Biotechnol. Prog., 2013
Impact of aeration strategy on CHO cell performance during antibody production
Authors: Velez‐Suberbie M. Lourdes , Tarrant Richard D. R. , Tait Andrew S. , Spencer Daniel I. R. , Bracewell Daniel G. 
Published: October 2012

AbstractStirred tank bioreactors using suspension adapted mammalian cells are typically used for the production of complex therapeutic proteins. The hydrodynamic conditions experienced by cells within this environment have been shown to directly impact growth, productivity, and product quality and therefore an improved understanding of the cellular response is critical. Here we investigate the sub‐lethal effects of different aeration strategies on Chinese hamster ovary cells during monoclonal antibody production. Two gas delivery systems were employed to study the presence and absence of the air–liquid interface: bubbled direct gas sparging and a non‐bubbled diffusive silicone membrane system. Additionally, the effect of higher gas flow rate in the sparged bioreactor was examined. Both aeration systems were run using chemically defined media with and without the shear protectant Pluronic F‐68 (PF‐68). Cells were unable to grow with direct gas sparging without PF‐68; however, when a silicone membrane aeration system was implemented growth was comparable to the sparged bioreactor with PF‐68, indicating the necessity of shear protectants in the presence of bubbles. The cultures exposed to increased hydrodynamic stress were shown by flow cytometry to have decreased F‐actin intensity within the cytoskeleton and enter apoptosis earlier. This indicates that these conditions elicit a sub‐lethal physiological change in cells that would not be detected by the at‐line assays which are normally implemented during cell culture. These physiological changes only result in a difference in continuous centrifugation performance under high flow rate conditions. Product quality was more strongly affected by culture age than the hydrodynamic conditions tested. © 2012 American Institute of Chemical Engineers Biotechnol. Prog., 2013.
Impact of incomplete revascularization in patients undergoing PCI for unprotected left main stem stenosis
Authors: Malkin Chris J. , Ghobrial Mina S.A. , Raina Tushar , Siotia Anjan , Morton Allison C. , Gunn Julian 
Published: October 2012

IntroductionPercutaneous revascularization of patients with multivessel and left main stem (LMS) disease may be incomplete and the impact of this is not well reported and may influence outcome. In this study we assessed the role of completeness of revascularization upon outcome after PCI for unprotected left main stem (uLMS) PCI in the “real world.”Materials and MethodConsecutive patients (n = 353) with uLMS disease were treated by PCI by a single operator with a policy of maximal feasible revascularization between 2000 and 2011. The SYNTAX score was calculated before and after PCI (residual SYNTAX score) to gauge the completeness of revascularization. The endpoints were mortality and repeat revascularization.ResultsMean age was 69 ± 11 years, baseline SYNTAX score was 33.4 ± 15, 53% were nonelective, 10% were in cardiogenic shock, and 45% were not surgical candidates. LMS bifurcation was involved in 74% and 2.0 ± 0.9 other vessels were diseased. Complete revascularization was achieved in 49% and was associated with reduced mortality compared with incomplete, at 30 days [5(2.9%) v 23(13%)], 1 year [9(5%) v 34(19%)], and 3 years [14(8%) v 46(26%)]; all P < 0.0001). Median rSYNTAX score was 1(0–11), 1‐year survival for the lowest, middle and highest tertiles of rSYNTAX were 1.7%, 3.1% and 7.3% (P < 0.0001), respectively. In multivariate analysis postprocedure rSYNTAX score independently predicted outcome but preprocedural SYNTAX score did not.ConclusionsFor unselected patients with uLMS treated by PCI, completeness of revascularization is associated with superior survival. The rSYNTAX score, a novel index of completeness of revascularization, independently predicts survival. Baseline SYNTAX score does not. © 2013 Wiley Periodicals, Inc.
Cost effectiveness of radial access for diagnostic cardiac catheterization and coronary intervention
Authors: Applegate Robert , Sacrinty Matthew , Schafer Pascha , Smith Justin , Gandhi Sanjay , Kutcher Michael , Santos Renato , Cecile Adam , Little William 
Published: October 2012

ObjectivesTo evaluate the cost effectiveness of diagnostic cardiac catheterizations (CATH) and coronary interventions (PCI) performed using radial artery (RA) access compared to femoral artery (FA) access.BackgroundCATH and PCI performed from the RA reduce access site complications compared to FA, but can increase procedure duration, and equipment and contrast use. Whether resulting increases in utilization costs are offset by reduced costs of complications is uncertain.MethodsIn all, 6,726 CATH and PCI (RA, 3,368; FA, 3,358) were performed from January 2009 to December 2011. Procedural costs and cost of access site complications were compared for propensity‐matched CATH (RA and FA, 1,222) and PCI (RA and FA, 570) throughout a complete transition of the lab from a preferred FA to preferred RA strategy.ResultsAdjusted mean total costs were $10 more (95% confidence interval $613 less to $610 more) for RA‐CATH versus FA‐CATH and $732 less ($1,345 less to $156 less) for RA‐PCI versus FA‐PCI. The incremental cost per vascular or bleeding complication avoided with RA‐CATH was $1,265, whereas RA was economically dominant with lower costs and fewer complications compared to FA for PCI and all procedures.ConclusionsRadial access for CATH and PCI reduced access site complications and overall costs compared to FA procedures with similar baseline clinical and procedural characteristics, making it an economically advantageous strategy. © 2012 Wiley Periodicals, Inc.
Bleeding outcomes after routine transradial primary angioplasty for acute myocardial infarction using eptifibatide and unfractionated heparin: A single‐center experience following the HORIZONS‐AMI trial
Authors: Moody William E. , Chue Colin D. , Ludman Peter F. , Chan Yik‐ki C. , Narayan Gautam , Millington Jenna M. , Townend Jonathan N. , Doshi Sagar N. 
Published: October 2012

ObjectivesWe sought to (1) determine the bleeding rates after primary percutaneous coronary intervention (PPCI) in our institution, where the default strategy has been transradial (TR) access in combination with unfractionated heparin (UFH) plus eptifibatide, and (2) compare these with the outcomes of patients treated with bivalirudin in HORIZONS‐AMI.BackgroundHORIZONS‐AMI demonstrated that in PPCI undertaken via the transfemoral route, routine use of bivalirudin was associated with lower bleeding rates and improved mortality compared to routine use of UFH plus glycoprotein IIb/IIIa inhibitor (GPI).MethodsThis was a single‐center prospective registry of consecutive patients undergoing PPCI from January 2009 to August 2011 at the Queen Elizabeth Hospital Birmingham, UK. Thirty‐day major bleeding was defined as per the HORIZONS‐AMI criteria and also according to TIMI and GUSTO scales.ResultsOf the 432 consecutive patients, 350 fulfilled entry criteria for HORIZONS‐AMI. In contrast with HORIZONS‐AMI, these subjects were older (62.5 ± 13.7 yr vs. 59.8 ± 11.1 yr, P < 0.05) with a higher rate of cardiogenic shock (6.3% vs. 0.8%, P < 0.0001). Despite this higher risk population, the rate of major bleeding was favorable (3.7% [95% CI: 2.0–6.3%] vs. 4.9% [4.0–6.1%], P = 0.32). Similarly, TIMI major bleeding (2.0% [0.8–4.1%] vs. 3.1% [2.3–3.4%], P = 0.10) and GUSTO severe or life‐threatening bleeding (0.6% [0.1–2.5%] vs. 0.4% [0.2–0.9%], P = 0.75) were comparable.ConclusionsRoutine TR access for PPCI using UFH plus GPI is associated with a low 30‐day rate of major bleeding equivalent to the bivalirudin arm of HORIZONS‐AMI. Default transradial access for PPCI permits routine use of a GPI without the penalty of high bleeding rates. © 2013 Wiley Periodicals, Inc.
Palladium‐Catalyzed Carbonylative Coupling of Aryl Iodides and Benzyl Acetylenes to 3‐Alkylidenefuran‐2‐ones under Mild Conditions and Its Density Functional Theory Modeling
Authors: Wu Xiao‐Feng , Jiao Haijun , Neumann Helfried , Beller Matthias 
Published: October 2012

AbstractA general and efficient method for the palladium‐catalyzed carbonylative coupling of aryl iodides to benzyl acetylenes has been developed. Various furanones have been prepared in excellent yields from their corresponding benzyl acetylenes at room temperature under a CO atmosphere. For aliphatic alkynes, their corresponding alkynones were obtained in good yields. Detailed DFT calculations have also been carried out to understand the reaction pathway and the most probable reaction mechanism has been proposed.
Current‐mode dual‐output ICCII‐based tunable universal biquadratic filter with low‐input and high‐output impedances
Authors: Chen Hua‐Pin 
Published: October 2012

SUMMARYA new tunable current‐mode (CM) biquadratic filter with three inputs and three outputs using three dual‐output inverting second‐generation current conveyors, three grounded resistors and two grounded capacitors is proposed. The proposed circuit exhibits low‐input impedance and high‐output impedance which is important for easy cascading in the CM operations. It can realize lowpass, bandpass, highpass, bandreject and allpass biquadratic filtering responses from the same topology. The circuit permits orthogonal controllability of the quality factor Q and resonance angular frequency ωo, and no component matching conditions or inverting‐type input current signals are imposed. All the passive and active sensitivities are low. Hspice simulation results are based on using TSMC 0.18 µm 1P6M process complementary metal oxide semiconductor technology and supply voltages ±0.9 V to verify the theoretical analysis. Copyright © 2012 John Wiley & Sons, Ltd.
Biomarker detection of rhGH Doping: an excretion study
Authors: Jing Jing , Zhou Xinmiao , He Chunji , Zhang Lisi , Yang Sheng , Xu Youxuan , Xie Minhao , Yan Yi , Su Hao , Wu Moutian 
Published: October 2012

The purpose of this research is to validate the biomarker‐based approach for the detection of doping with recombinant human growth hormone (rhGH) in sport. The GH‐2000 project proposed an indirect method for the detection of exogenously administered growth hormone (GH) based on the measurement of the GH‐dependent markers: insulin‐like growth factor‐I (IGF‐I) and Type III pro‐collagen (P‐III‐P). These markers rise in a dose‐dependent manner after GH application. In this study, the concentrations of IGF‐I, IGF‐BP3, and P‐III‐P in serum were determined to provide further incentives for the implementation of this detection assay in modern anti‐doping programmes. This paper reports on an administration study of rhGH involving 25 Chinese male volunteers at a dose of 0.1 IU /kg/day for a continuous 14‐day period.We observed that the serum IGF‐I concentration increased rapidly in the rhGH treatment group and showed significantly higher levels compared to baseline between days 4 and day 16 after administration. Although the response of P‐III‐P to rhGH administration was delayed compared to the IGF‐I axis, the P‐III‐P concentration remained increased for a longer period (from day 4 to day 28). Statistical analysis was carried out to establish a discriminant formula with Statistical Product and Service Solutions (SPSS) concluding that the biomarker methodology is valid and universally applicable. Copyright © 2012 John Wiley & Sons, Ltd.
The Skeletal site‐specific role of connective tissue growth factor in prenatal osteogenesis
Authors: Lambi Alex G. , Pankratz Talia L. , Mundy Christina , Gannon Maureen , Barbe Mary F. , Richtsmeier Joan T. , Popoff Steven N. 
Published: October 2012

AbstractBackground: Connective tissue growth factor (CTGF/CCN2) is a matricellular protein that is highly expressed during bone development. Mice with global CTGF ablation (knockout, KO) have multiple skeletal dysmorphisms and perinatal lethality. A quantitative analysis of the bone phenotype has not been conducted. Results: We demonstrated skeletal site‐specific changes in growth plate organization, bone microarchitecture, and shape and gene expression levels in CTGF KO compared with wild‐type mice. Growth plate malformations included reduced proliferation zone and increased hypertrophic zone lengths. Appendicular skeletal sites demonstrated decreased metaphyseal trabecular bone, while having increased mid‐diaphyseal bone and osteogenic expression markers. Axial skeletal analysis showed decreased bone in caudal vertebral bodies, mandibles, and parietal bones in CTGF KO mice, with decreased expression of osteogenic markers. Analysis of skull phenotypes demonstrated global and regional differences in CTGF KO skull shape resulting from allometric (size‐based) and nonallometric shape changes. Localized differences in skull morphology included increased skull width and decreased skull length. Dysregulation of the transforming growth factor‐β‐CTGF axis coupled with unique morphologic traits provides a potential mechanistic explanation for the skull phenotype. Conclusions: We present novel data on a skeletal phenotype in CTGF KO mice, in which ablation of CTGF causes site‐specific aberrations in bone formation. Developmental Dynamics, 2012. © 2012 Wiley Periodicals, Inc.
RGMa and RGMb expression pattern during chicken development suggest unexpected roles for these repulsive guidance molecules in notochord formation, somitogenesis, and myogenesis
Authors: Jorge Erika Cristina , Ahmed Mohi U. , Bothe Ingo , Coutinho Luiz Lehmman , Dietrich Susanne 
Published: October 2012

AbstractBackground: Repulsive guidance molecules (RGM) are high‐affinity ligands for the Netrin receptor Neogenin, and they are crucial for nervous system development including neural tube closure; neuronal and neural crest cell differentiation and axon guidance. Recent studies implicated RGM molecules in bone morphogenetic protein signaling, which regulates a variety of developmental processes. Moreover, a role for RGMc in iron metabolism has been established. This suggests that RGM molecules may play important roles in non‐neural tissues. Results: To explore which tissues and processed may be regulated by RGM molecules, we systematically investigated the expression of RGMa and RGMb, the only RGM molecules currently known for avians, in the chicken embryo. Conclusions: Our study suggests so far unknown roles of RGM molecules in notochord, somite and skeletal muscle development. Developmental Dynamics, 2012. © 2012 Wiley Periodicals, Inc.
Modelling the effects of the mountain pine beetle on snowmelt in a subalpine forest
Authors: Perrot Danielle , Molotch Noah P. , Musselman Keith N. , Pugh Evan T. 
Published: October 2012

ABSTRACTThe recent mountain pine beetle epidemic in the Colorado River Basin has resulted in widespread tree mortality in pine stands across the Colorado Plateau. Because of complex micro‐scale (i.e. tree well scale) interactions between vegetation and snow processes, one of the most significant issues resulting from this epidemic is the potential hydrologic impacts of the effects of changing forest structure. Using SNTHERM, we conducted a comparative modelling scenario analysis of the snowpack along a transect between two trees over the course of the snow ablation season (28 February–30 June) under four forest stand conditions to assess changes in snowpack characteristics because of loss of canopy biomass. We found that the red phase scenario (intermediate phase of tree death) exhibited a 4‐day earlier snow disappearance date than the living stand scenario and grey phase scenario (advanced phase of tree death), although the timing of isothermal conditions at 0 °C was identical. The modelled clearcut scenario snowpack became isothermal at 0 °C 10 days earlier than the living, red phase, or grey phase scenarios. The clearcut modelling scenario also exhibited the greatest homogenization of snow properties, and the spatio‐temporal distribution of snow disappearance at the tree well scale was 70% as variable as the living, red phase and grey phase modelling scenarios. These results provide insight to the processes responsible for changing hydrologic dynamics in snow‐dominated forest ecosystems with the onset of vegetation stress and death and may help inform future forest management strategies.Copyright © 2012 John Wiley & Sons, Ltd.
Sustainable Development Indicators: From Statistics to Policy
Authors: Garnåsjordet Per Arild , Aslaksen Iulie , Giampietro Mario , Funtowicz Silvio , Ericson Torgeir 
Published: October 2012

ABSTRACTSustainable development indicators (SDIs) may have good potential to bring environmental concerns to the policy agenda. However, different understandings of sustainability, definitions of SDIs and measurement procedures may give completely different assessments of whether society moves towards a sustainable development path or not. Compilation of statistical indicators for environmental change and sustainability comprises not only a selection of facts in some technical sense, as the choices involved are conditioned by societal interests and implicit values embedded in the data‐generating processes. This implies that statistical offices cannot ignore the role that values play in the generation of accurate data sets. To give an assessment of sustainability, we need not only to address historical trends but also to evaluate policy choices made today and how they may influence future development. SDI sets should be evaluated according to how they contribute to deliberation on sustainability in learning processes involving participants beyond the science–policy interface. Copyright © 2012 John Wiley & Sons, Ltd and ERP Environment.