bluuebunny/crossref_metadata_2025 huggingface dataset:
Skeletal development inPan paniscuswith comparisons toPan troglodytes
Authors: Bolter Debra R. , Zihlman Adrienne L.
Published: February 2012

Fusion of skeletal elements provides markers for timing of growth and is one component of a chimpanzee's physical development. Epiphyseal closure defines bone growth and signals a mature skeleton. Most of what we know about timing of development in chimpanzees derives from dental studies onPan troglodytes. Much less is known about the sister species,Pan paniscus, with few in captivity and a wild range restricted to central Africa. Here, we report on the timing of skeletal fusion for female captiveP. paniscus(n= 5) whose known ages range from 0.83 to age 11.68 years. Observations on the skeletons were made after the individuals were dissected and bones cleaned. Comparisons with 10 female captiveP. troglodytesconfirm a generally uniform pattern in the sequence of skeletal fusion in the two captive species. We also compared theP. paniscusto a sample of three unknown‐aged female wildP. paniscus, and 10 female wildP. troglodytesof known age from the Taï National Park, Côte d'Ivoire. The sequence of teeth emergence to bone fusion is generally consistent between the two species, with slight variations in late juvenile and subadult stages. The direct‐age comparisons show that skeletal growth in captiveP. paniscusis accelerated compared with both captive and wildP. troglodytespopulations. The skeletal data combined with dental stages have implications for estimating the life stage of immature skeletal materials of wildP. paniscusand for more broadly comparing the skeletal growth rates among captive and wild chimpanzees (Pan),Homo sapiens, and fossil hominins. Am J Phys Anthropol 2012. © 2012 Wiley Periodicals, Inc.
A fully automated data reduction pipeline for the FRODOSpec integral field spectrograph
Authors: Barnsley R.M. , Smith R.J. , Steele I.A.
Published: February 2012

A fully autonomous data reduction pipeline has been developed for FRODOSpec, an optical fibre‐fed integral field spectrograph currently in use at the Liverpool Telescope. This paper details the process required for the reduction of data taken using an integral field spectrograph and presents an overview of the computational methods implemented to create the pipeline. Analysis of errors and possible future enhancements are also discussed (© 2011 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
The color‐magnitude diagram of NGC 2264
Authors: Turner D.G.
Published: February 2012

Existing photometry for NGC 2264 tied to the Johnson & Morgan (1953) UBV system is reexamined and, in the case of the original observations by Walker (1956), reanalyzed in order to generate a homogeneous data set for cluster stars. Color terms and a Balmer discontinuity effect in Walker's observations were detected and corrected, and the homogenized data were used in a new assessment of the cluster reddening, distance, and age. Average values of EB – V = 0.075 ± 0.003 s.e. and V0 –MV = 9.45 ± 0.03 s.e. (d = 777 ± 12 pc) are obtained, in conjunction with an inferred cluster age of ∼5.5 × 106 yr from pre‐main‐sequence members and the location of the evolved, luminous, O7 V((f)) dwarf S Mon relative to the ZAMS. The cluster main sequence also contains gaps that may have a dynamical origin. The dust responsible for the initial reddening towards NGC 2264 is no more than 465 pc distant, and there are numerous, reddened and unreddened, late‐type stars along the line of sight that are difficult to separate from cluster members by standard techniques, except for a small subset of stars on the far side of the cluster embedded in its gas and dust and background B‐type ZAMS members of Mon OB2. A compilation of likely NGC 2264 members is presented. Only 3 of the 4 stars recently examined by asteroseismology appear to be likely cluster members. NGC 2264 is also noted to be a double cluster, which has not been mentioned previously in the literature (© 2011 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Power spectral distribution of the BL Lacertae object S5 0716+714
Authors: Mocanu G.R. , Marcu A.
Published: February 2012

Observational data in the BVRI bands of the variable BL Lacertae object S5 0716+714 are discussed from the point of view of its power spectral distribution (PSD). A model of the type P (f) = βf–1 [1 + (f /δ)α–1]–1 + γ is fitted to the data for four null hypothesis and the Bayesian p parameter for the fits is calculated. Spectral slopes with values ranging from 1.083 to 2.65 are obtained, with medium values for each band of $ \bar \alpha_B $ = 2.028, $ \bar \alpha_V $ = 1.809, $ \bar \alpha_R $ = 1.932 and $ \bar \alpha_I $ = 1.54 respectively. These values confirm conclusions of previous studies, namely that the source is turbulent. Two disk models, the standard prescription of the Shakura‐Sunyaev disk and magnetized disks exhibiting magneto‐rotational instabilities, were discussed. We found that it is unlikely that they explain this set of observational data (© 2011 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Decision Strategies and the Confidence–Accuracy Relationship in Face Recognition
Authors: Weber Nathan , Woodard Libbey , Williamson Paul
Published: February 2012

The decision strategy used to select a choice set from an array of alternative options is known to affect the composition of the final choice set. Specifically, individuals incorporate more answers into their choice set when it is created by eliminating implausible items than when the set is created through the inclusion of plausible options. This difference is accounted for in a decision framework that posits a general reluctance to change the status quo (i.e., actively include or exclude an item). We extended this work to investigate, not only the decisions themselves, but also metacognitive judgments (i.e., confidence in the accuracy of the choice set). In two face recognition experiments, we tested the impact of decision strategy (Experiment 1) and confidence judgment strategy (Experiment 2) on the confidence–accuracy relationship. In Experiment 1, participants completed two blocks of recognition trials, one under inclusion (marking previously seen faces) and one under elimination (marking previously unseen faces) instructions. We observed superior resolution (i.e., discrimination between correct and incorrect) for inclusion trials, but only when they were completed prior to use of the elimination strategy. In Experiment 2, all participants completed face recognition trials under inclusion instructions, but we manipulated the strategy used to assess confidence. Again, we observed a significant impact of strategy on confidence–accuracy resolution. Thus, we observed that both the strategy employed to reach a decision and that employed to assess confidence affected the confidence–accuracy relationship. We discuss theoretical and applied (particularly for eyewitness identification and multiple‐choice testing) implications. Copyright © 2012 John Wiley & Sons, Ltd.
CREB signalling in neural stem/progenitor cells: Recent developments and the implications for brain tumour biology
Authors: Mantamadiotis Theo , Papalexis Nikos , Dworkin Sebastian
Published: February 2012

This paper discusses the evidence for the role of CREB in neural stem/progenitor cell (NSPC) function and oncogenesis and how these functions may be important for the development and growth of brain tumours. The cyclic‐AMP response element binding (CREB) protein has many roles in neurons, ranging from neuronal survival to higher order brain functions such as memory and drug addiction behaviours. Recent studies have revealed that CREB also has a role in NSPC survival, differentiation and proliferation. Recent work has shown that over‐expression of CREB in transgenic animals can impart oncogenic properties on cells in various tissues and that aberrant CREB expression is associated with tumours in patients. It is the central position of CREB, downstream of key developmental and growth signalling pathways, which give CREB the ability to influence a spectrum of cell activities, such as cell survival, growth and differentiation in both normal and cancer cells.
Consolidated bioprocessing (CBP) of AFEX™‐pretreated corn stover for ethanol production using Clostridium phytofermentans at a high solids loading
Authors: Jin Mingjie , Gunawan Christa , Balan Venkatesh , Dale Bruce E.
Published: February 2012

Consolidated bioprocessing (CBP) using Clostridium phytofermentans (ATCC 700394) on ammonia fiber expansion (AFEX™)‐treated corn stover (AFEX™‐CS) at a low solids loading showed promising results [Jin et al. (2011) Biotechnol Bioeng 108(6): 1290–1297]. However, industrial relevant process requires high solids loading. Therefore, we studied high solids loading CBP performance on AFEX™‐CS. The factors potentially affecting the performance including solids loading, CBP products acetate and ethanol, and degradation products resulting from pretreatment were investigated. At 4% (w/w) glucan loading, C. phytofermentans performed well on AFEX™‐CS with no nutrients supplementation and reached similar sugar conversions as a fermentation with nutrients supplementation. A glucan conversion of 48.9% and a xylan conversion of 77.9% were achieved after 264 h with 7.0 g/L ethanol and 8.8 g/L acetate produced. Relatively high concentrations of acetate produced at high solids loading was found to be the major factor limiting the CBP performance. Degradation products in AFEX™‐CS helped enhance ethanol production. Biotechnol. Bioeng. 2012; 109:1929–1936. © 2012 Wiley Periodicals, Inc.
Limiting cell aggregation during mesenchymal stem cell expansion on microcarriers
Authors: Ferrari Caroline , Balandras Frédérique , Guedon Emmanuel , Olmos Eric , Chevalot Isabelle , Marc Annie
Published: February 2012

Mesenchymal stem cells (MSC) are known to be a valuable cell source for tissue engineering and regenerative medicine. However, one of the main limiting steps in their clinical use is the amplification step. MSC expansion on microcarriers has emerged during the last few years, fulfilling the lack of classical T‐flasks expansion. Even if the therapeutic potential of MSC as aggregates has been recently highlighted, cell aggregation during expansion has to be avoided. Thus, MSC culture on microcarriers has still to be improved, notably concerning cell aggregation prevention. The aim of this study was to limit cell aggregation during MSC expansion on Cytodex‐1®, by evaluating the impact of several culture parameters. First, MSC cultures were performed at different agitation rates (0, 25, and 75 rpm) and different initial cell densities (25 and 50 × 106 cell g−1 Cytodex‐1®). Then, the MSC aggregates were put into contact with additional available surfaces (T‐flask, fresh and used Cytodex‐1®) at different times (before and after cell aggregation). The results showed that cell aggregation was partly induced by agitation and prevented in static cultures. Moreover, cell aggregation was dependent on cell density and correlated with a decrease in the total cell number. It was however shown that the aggregated organization could be dissociated when in contact with additional surfaces such as T‐flasks or fresh Cytodex‐1® carriers. Finally, cell aggregation could be successfully limited in spinner flask by adding fresh Cytodex‐1® carriers before its onset. Those results indicated that MSC expansion on agitated Cytodex‐1® microcarriers could be performed without cell aggregation, avoiding a decrease in total cell number. © 2012 American Institute of Chemical Engineers Biotechnol. Prog., 2012
Hydrogen Bonds: A Structural Insight into Ionic Liquids
Authors: Dong Kun , Zhang Suojiang
Published: February 2012

Ionic liquids (ILs) have attracted intensive attention in academia and industry due to their unique properties and potential applications. Nowadays, much interest is focused on finding out what is the main force that determines the properties of ionic liquids. Intuitively like NaCl, in high‐temperature molten salt (HTMS) the electrostatic Coulomb force is regarded as the dominant factor that determines the behaviors of ILs. However, a large amount of evidence indicates that such a molten‐salt‐based simplified explanation is not consistent with the corresponding experimental results. Besides the Coulomb force, the hydrogen bond is another important noncovalent interaction in the IL and is closely related to some important properties and applications, as suggested in some new research results. Therefore in this review, we present results concerning the hydrogen bond in ILs, from the perspective of experiment and calculation, to shed light on its effects and roles. The deep insights into structure, in particular the hydrogen bonds, can provide us with a rational design for the new ILs to fulfill the demands in some complicated chemical processes.
A New Benzotriazole‐Mediated Stereoflexible Gateway to Hetero‐2,5‐diketopiperazines
Authors: Monbaliu Jean‐Christophe M. , Hansen Finn K. , Beagle Lucas K. , Panzner Matthew J. , Steel Peter J. , Todadze Ekaterina , Stevens Christian V. , Katritzky Alan R.
Published: February 2012

Open chain Cbz‐L‐aa1‐L‐Pro‐Bt (Bt=benzotriazole) sequences were converted into either the corresponding trans‐ or cis‐fused 2,5‐diketopiperazines (DKPs) depending on the reaction conditions. Thermodynamic tandem cyclization/epimerization afforded selectively the corresponding trans‐DKPs (69–75 %). Complementarily, tandem deprotection/cyclization led to the cis‐DKPs (65–72 %). A representative set of proline‐containing cis‐ and trans‐DKPs has been prepared. A mechanistic investigation, based on chiral HPLC, kinetics, and computational studies enabled a rationalization of the results.
Chemical Synthesis of the Cardiotonic Steroid Glycosides and Related Natural Products
Authors: Heasley Brian
Published: February 2012

The active components from the extracts of Digitalis, cardiotonic steroid glycosides, have been ingested by humans for more than 200 years as a medicinal therapy for heart failure and abnormal heart rhythms. The positive inotropic activity of the cardiotonic steroids that mediates clinically useful physiological effects in patients has been attributed largely to a high affinity inhibitory interaction with the extracellular surface of the membrane‐bound sodium pump (Na+/K+‐ATPase). However, previously unrecognized intracellular signaling pathways continue to be uncovered. This Review examines both partial and de novo synthetic approaches to the medicinally important and structurally captivating cardenolide and bufadienolide steroid families, with an emphasis on the stereocontrolled construction of the pharmacophoric aglycone (genin) framework.
Modelling of transport of two proppant‐laden immiscible power‐law fluids through an expanding fracture
Authors: Lakhtychkin Alexander , Eskin Dmitry , Vinogradov Oleg
Published: February 2012

Hydraulic fracturing technology is one of the most popular and efficient reservoir stimulation techniques in oil and gas industry since it allows significant increase of the hydrocarbon production rate. A possible advancement of this technology involves consequent pumping of several immiscible fluids laden with solid particles (proppant) into a fracture. This technique has a potential for better control of the proppant placement and, thus, a better control of the fracture shape. The major result of the present work is a mathematical model and a computational code for investigation of a flow of two immiscible slurries inside an expanding fracture. © 2012 Canadian Society for Chemical Engineering
The effect of thin gap insertion layer on InP nanostructure grown by metal–organic vapour phase epitaxys
Authors: Han Soe Soe , Panyakeow Somsak , Ratanathammaphan Somchai , Higo Akio , Yunpeng Wang , Deura Momoko , Sugiyama Masakasu , Nakano Yoshiaki
Published: February 2012

The effect of thin GaP insertion layers on the structural and optical properties of InP/In0.49Ga0.51P self‐assembled quantum dots (SAQDs) on GaAs (001) substrate grown by metal–organic vapour phase epitaxy has been reported. The properties of InP/In0.49Ga0.51P SAQDs are modified when a thin (1–4 ML) GaP layer is inserted underneath the InP quantum dots (QDs). Deposition of the GaP insertion layer affects the dot dimension and improves the size uniformity. The density, dimension and uniformity of InP QDs strongly depend on the GaP insertion layer thickness. This variation in QD size is a result of a material nucleation effect caused by atomic intermixing between the InP QDs and underlying GaP insertion layer and surface energy. The insertion of GaP layer led to tuning the emission wavelength and narrowing of full width at half maximum (FWHM) when they are characterised by PL measurements at room temperature. © 2012 Canadian Society for Chemical Engineering
Synthesis and Biological Evaluation of Acridine Derivatives as Antimalarial Agents
Authors: Yu Xiao‐Min , Ramiandrasoa Florence , Guetzoyan Lucie , Pradines Bruno , Quintino Edgar , Gadelle Daniele , Forterre Patrick , Cresteil Thierry , Mahy Jean‐Pierre , Pethe Stéphanie
Published: February 2012

New N‐alkylaminoacridine derivatives attached to nitrogen heterocycles were synthesized, and their antimalarial potency was examined. They were tested in vitro against the growth of Plasmodium falciparum, including chloroquine (CQ)‐susceptible and CQ‐resistant strains. This biological evaluation has shown that the presence of a heterocyclic ring significantly increases the activity against P. falciparum. The best compound shows a nanomolar IC50 value toward parasite proliferation on both CQ‐susceptible and CQ‐resistant strains. The antimalarial activity of these new acridine derivatives can be explained by the two mechanisms studied in this work. First, we showed the capacity of these compounds to inhibit heme biocrystallization, a detoxification process specific to the parasite and essential for its survival. Second, in our search for alternative targets, we evaluated the in vitro inhibitory activity of these compounds toward Sulfolobus shibatae topoisomerase VI‐mediated DNA relaxation. The preliminary results obtained reveal that all tested compounds are potent DNA intercalators, and significantly inhibit the activity of S. shibatae topoisomerase VI at concentrations ranging between 2.0 and 2.5 μM.
Duality in simple single atomic type crystal structures
Authors: Ruhnow M.
Published: February 2012

Crystal structures can be interpreted as a systematic arrangement of atoms and interstices. Their spatial arrangement follows the duality principle. By using mathematical polyhedra it is possible to show an overall scheme in the simple crystal structures that is possibly hidden from view by the utilization of the hard‐sphere‐model or charge density distributions. In addition there is a dual connection between the shape of the atoms and the arrangement of these atoms (i.e. the crystal structure). Therefore, the shape is expected to control the arrangement, with some possible feedback from the arrangement on the shape. On the basis of the dual principle a connection can be recognized between some crystal structures. Allotrope transitions can also be explained by using this principle. Moreover, physical parameters which are connected to the crystal structure like atomic arrangement and E(k) of delocalized electrons also follow the duality principle. Consequently, it is possible to conclude that duality represents a basic principle of the simple single atomic type crystal structures. (© 2012 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Correlating dynamic amino acid properties with success rate of crystallization of proteins from Bacteroides vulgatus
Authors: Yan Shaomin , Wu Guang
Published: February 2012

To enhance the success rate of protein crystallization, many studies were conducted to determine the relationship between amino acid properties and the success rate of protein crystallization. Although those were successful, new efforts should be made to search for the new factors, which affect protein crystallization. In this study, two dynamic amino acid properties were used to correlate with the success rate of crystallization of proteins from Bacteroides vulgatus, because the amino acid properties used in previous studies were steady. As previously done, logistic regression and neural network were used to model that relationship, and the results were compared against those obtained from each of 532 amino acid properties, which severed as benchmark. The results demonstrated that dynamic amino acid properties should be taken into consideration of protein crystallization. (© 2012 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Control Method for Harmonic Voltage Injection to Achieve Noise Reduction in Position‐Sensorless Control of Permanent‐Magnet Synchronous Motors at Low Speeds
Authors: Taniguchi Shun , Homma Toshihiro , Wakao Shinji , Kondo Keiichiro , Yoneyama Takashi
Published: February 2012

In this study, we examine the relationship between harmonic voltage injection, acoustic noise, and position estimation performance in a PMSM when a position‐sensorless control method involving harmonic voltage injection is used at low speeds. Further, we propose a novel control method for voltage injection; this method can be used to reduce acoustic noise in the motor. The proposed control method is verified by performing numerical simulations and carrying out experiments using a four‐pole, 2‐kW, 2100‐rpm IPMSM (interior permanent‐magnet synchronous motor). © 2012 Wiley Periodicals, Inc. Electr Eng Jpn, 179(3): 49–56, 2012; Published online in Wiley Online Library (wileyonlinelibrary.com). DOI 10.1002/eej.21246
Supramolecular Adducts of Negatively Charged Lanthanide(III) DOTP Chelates and Cyclodextrins Functionalized with Ammonium Groups: Mass Spectrometry and Nuclear Magnetic Resonance Studies
Authors: Pereira Giovannia A. , Peters Joop A. , Terreno Enzo , Delli Castelli Daniela , Aime Silvio , Laurent Sophie , Vander Elst Luce , Muller Robert N. , Geraldes Carlos F. G. C.
Published: February 2012

The interaction of the negatively charged Ln3+ chelate Ln–DOTP with β‐ and γ‐cyclodextrins bearing ammonium groups at the upper rim (CD+s) was investigated using mass spectrometry and NMR spectroscopic techniques. Mass spectroscopy shows the presence of 1:1 adducts of Ln–DOTP and both β‐ or γ‐CD+. The peak intensities increased upon increasing the pH of the samples from 7 to 9.0, suggesting an increase in the strength of the interaction. Lanthanide induced 1H NMR chemical shifts and relaxation ratesmeasured in aqueous solutions confirmed the presence of these adducts. The strength of the interactions appeared to be dependent on the pH, reflecting the strong electrostatic interactions between the oppositely charged host CD+ and guest Ln–DOTP chelate. Evaluation of the lanthanide induced relaxation rates showed that the Ln–DOTP does not enter the cavity of the CDs, but remains above it with a distance of 10–11 Å between the Ln3+ ion and the centre of the CD. Molecular modelling indicated that hydrogen bonds between the functionalized groups participating in the interaction sites contribute to the adduct stabilization. The apparent binding constants at pH 7 and 9 were obtained by using relaxometric measurements at 9 MHz. Fitting the NMRD profiles showed an increase in the number of second‐sphere water molecules surrounding the phosphonate pendant arms of the Ln–DOTP chelate upon its interaction with the CDs. A brief description of the PARACEST properties of the supramolecular systems formed by Tm–DOTP and the positively charged CDs is presented. Both CDs display a shift of the saturation transfer peaks of the ammonium functions by the Tm complex, with an accentuated effect observed for the γ‐CD derivative.
Relevance of DHA‐containing lysophospholipids
Authors: Lagarde Michel , Bernoud‐Hubac Nathalie
Published: February 2012

In this issue of the European Journal of Lipid Science and Technology, Jin et al. [114–122] report on the anti‐inflammatory effect of docosahexaenoyl‐lysophosphatidylcholine with even a stronger effect when the docosahexaenoic acyl is oxygenated on its carbon 17.

See accompanying article http://dx.doi.org/10.1002/ejlt.201100169
Mobile localisation with TOA, AOA and Doppler estimation in NLOS environments
Authors: Xie Yaqin , Wang Yan , Wu Bo , You Xiaohu
Published: February 2012

In this paper, we present a novel nonline‐of‐sight (NLOS) positioning method for a mobile station (MS). Under the assumption of the Gaussian scatter density model (GSDM), the proposed scheme makes full use of the NLOS single reflection paths to improve the MS location accuracy. For the moving MS, a constrained optimisation method is proposed to jointly estimate the unknown MS and scatters' locations with time of arrival, angle of arrival and Doppler‐shift frequency measurements. The proposed optimisation method is solved by a novel grid search algorithm (GSA), which combines the advantages of constrained optimisation and statistical signal processing methods. The MS location accuracy is further improved by using the weighted mean GSA instead of the arithmetic mean GSA. We also compared the location accuracy with the Cramer–Rao lower bound. Simulation results show that the proposed method outperforms those existing methods significantly. Copyright © 2012 John Wiley & Sons, Ltd.
Sensitivity analysis of the build decision for carbon capture and sequestration projects
Authors: Fischbeck Paul S. , Gerard David , McCoy Sean T.
Published: February 2012

Carbon capture and sequestration (CCS) is a technology that could allow for continued use of fossil fuels in a carbon‐constrained world, smoothing the transition to non‐fossil energy sources. Our objective is to assess the commercial viability of CCS given pervasive future uncertainties, particularly uncertainties about future natural gas and CO2 prices. Using data from the Integrated Environmental Control Model (IECM), we develop an interactive Excel‐based spreadsheet tool to compare levelized‐average costs of four different new‐construction 500 MW power plants: natural gas combined cycle (NGCC) with CCS, NCGG without CCS, supercritical coal with CCS, and supercritical coal without CCS. With low natural gas prices, the NGCC without the sequestration option is the dominant technology. Overall, CCS projects for either natural gas or coal projects are unlikely to be the lowest‐cost option for CO2 prices less than $50 per ton. Finally, we examine several potential policy levers that could affect the deployment of CCS. © 2012 Society of Chemical Industry and John Wiley & Sons, Ltd
Proteome and computational analyses reveal new insights into the mechanisms of hepatitis C virus–mediated liver disease posttransplantation
Authors: Diamond Deborah L. , Krasnoselsky Alexei L. , Burnum Kristin E. , Monroe Matthew E. , Webb-Robertson Bobbie-Jo , McDermott Jason E. , Yeh Matthew M. , Dzib Jose Felipe Golib , Susnow Nathan , Strom Susan , Proll Sean C. , Belisle Sarah E. , Purdy David E. , Rasmussen Angela L. , Walters Kathie-Anne , Jacobs Jon M. , Gritsenko Marina A. , Camp David G. , Bhattacharya Renuka , Perkins James D. , Carithers Robert L. , Liou Iris W. , Larson Anne M. , Benecke Arndt , Waters Katrina M. , Smith Richard D. , Katze Michael G.
Published: February 2012

Liver transplant tissues offer the unique opportunity to model the longitudinal protein abundance changes occurring during hepatitis C virus (HCV)-associated liver disease progression in vivo. In this study, our goal was to identify molecular signatures, and potential key regulatory proteins, representative of the processes influencing early progression to fibrosis. We performed global protein profiling analyses on 24 liver biopsy specimens obtained from 15 HCV+ liver transplant recipients at 6 and/or 12 months posttransplantation. Differentially regulated proteins associated with early progression to fibrosis were identified by analysis of the area under the receiver operating characteristic curve. Analysis of serum metabolites was performed on samples obtained from an independent cohort of 60 HCV+ liver transplant patients. Computational modeling approaches were applied to identify potential key regulatory proteins of liver fibrogenesis. Among 4,324 proteins identified, 250 exhibited significant differential regulation in patients with rapidly progressive fibrosis. Patients with rapid fibrosis progression exhibited enrichment in differentially regulated proteins associated with various immune, hepatoprotective, and fibrogenic processes. The observed increase in proinflammatory activity and impairment in antioxidant defenses suggests that patients who develop significant liver injury experience elevated oxidative stresses. This was supported by an independent study demonstrating the altered abundance of oxidative stress-associated serum metabolites in patients who develop severe liver injury. Computational modeling approaches further highlight a potentially important link between HCV-associated oxidative stress and epigenetic regulatory mechanisms impacting on liver fibrogenesis. Conclusion: Our proteome and metabolome analyses provide new insights into the role for increased oxidative stress in the rapid fibrosis progression observed in HCV+ liver transplant recipients. These findings may prove useful in prognostic applications for predicting early progression to fibrosis. (HEPATOLOGY 2012;56:28–38)
Comparative proteomic analysis of rat hepatic stellate cell activation: A comprehensive view and suppressed immune response
Authors: Ji Juling , Yu Feng , Ji Qiuhong , Li Zhiyao , Wang Kuidong , Zhang Jinsheng , Lu Jinbiao , Chen Li , E Qun , Zeng Yaoying , Ji Yuhua
Published: February 2012

Elucidation of the molecular events underlying hepatic stellate cell (HSC) activation is an essential step toward understanding the biological properties of HSC and clarifying the potential roles of HSCs in liver fibrosis and other liver diseases, including hepatocellular carcinoma. High-throughput comparative proteomic analysis based on isobaric tags for relative and absolute quantitation (iTRAQ) labeling combined with online two-dimensional nanoscale liquid chromatography and tandem mass spectrometry (2D nano-LC-MS/MS) were performed on an in vitro HSC activation model to obtain a comprehensive view of the protein ensembles associated with HSC activation. In total, 2,417 proteins were confidently identified (false discovery rate <1%), of which 2,322 proteins were quantified. Compared with quiescent HSCs, 519 proteins showed significant differences in activated HSCs (≥3.0-fold). Bioinformatics analyses using Ingenuity Pathway Analysis revealed that the 319 up-regulated proteins represented multiple cellular functions closely associated with HSC activation, such as extracellular matrix synthesis and proliferation. In addition to the well-known markers for HSC activation, such as α-smooth muscle actin and collagen types 1 and 3, some novel proteins potentially associated with HSC activation were identified, while the 200 down-regulated proteins were primarily related to immune response and lipid metabolism. Most intriguingly, the top biological function, top network, and top canonical pathway of down-regulated proteins were all involved in immune responses. The expression and/or biological function of a set of proteins were properly validated, especially Bcl2-associated athanogene 2, BAG3, and B7H3. Conclusion: The present study provided the most comprehensive proteome profile of rat HSCs and some novel insights into HSC activation, especially the suppressed immune response. (HEPATOLOGY 2012;56:332–349)
HCV RNA levels in a multiethnic cohort of injection drug users: Human genetic, viral and demographic associations
Authors: Uccellini Lorenzo , Tseng Fan-Chen , Monaco Alessandro , Shebl Fatma M. , Pfeiffer Ruth , Dotrang Myhanh , Buckett Dianna , Busch Michael P. , Wang Ena , Edlin Brian R. , Marincola Francesco M. , O'Brien Thomas R.
Published: February 2012

In patients with chronic hepatitis C, the hepatitis C virus (HCV) RNA level is an important predictor of treatment response. To explore the relationship of HCV RNA with viral and demographic factors, as well as IL28B genotype, we examined viral levels in an ethnically diverse group of injection drug users (IDUs). Between 1998 and 2000, the Urban Health Study (UHS) recruited IDUs from street settings in San Francisco Bay area neighborhoods. Participants who were positive by HCV enzyme immunoassay were tested for HCV viremia by a branched-chain DNA assay. HCV genotype was determined by sequencing the HCV nonstructural 5B protein region. For a subset of participants, IL28B rs12979860 genotype was determined by Taqman. Among 1,701 participants with HCV viremia, median age was 46 years and median duration of injection drug use was 26 years; 56.0% were African American and 34.0% were of European ancestry (non-Hispanic). Human immunodeficiency virus type 1 (HIV-1) prevalence was 13.9%. The overall median HCV RNA level was 6.45 log10 copies/mL. In unadjusted analyses, higher levels were found with older age, male gender, African-American ancestry, hepatitis B virus infection, HIV-1 infection, and IL28B rs12979860-CC genotype; compared to participants infected with HCV genotype 1, HCV RNA was lower in participants with genotypes 3 or 4. In an adjusted analysis, age, gender, racial ancestry, HIV-1 infection, HCV genotype, and IL28B rs12979860 genotype were all independently associated with HCV RNA. Conclusion: The level of HCV viremia is influenced by a large number of demographic, viral, and human genetic factors. (HEPATOLOGY 2012;56:86–94)
Laser captured hepatocytes show association of butyrylcholinesterase gene loss and fibrosis progression in hepatitis C-infected drug users
Authors: Munshaw Supriya , Hwang Hyon S. , Torbenson Michael , Quinn Jeffrey , Hansen Kasper D. , Astemborski Jacquie , Mehta Shruti H. , Ray Stuart C. , Thomas David L. , Balagopal Ashwin
Published: February 2012

Chronic hepatitis C virus (HCV) infection is complicated by hepatic fibrosis. Hypothesizing that early fibrogenic signals may originate in cells susceptible to HCV infection, hepatocyte gene expression was analyzed from persons with chronic HCV at different stages of liver fibrosis. Four HCV-infected subjects with precirrhosis liver fibrosis (Ishak fibrosis 3-5) were matched for age, race, and gender to five HCV-infected subjects with no evidence of fibrosis (Ishak fibrosis 0). Hepatocytes from each subject were isolated from liver biopsies using laser capture microdissection. Transcriptome profiling was performed on hepatocyte RNA using hybridization arrays. We found that hepatocytes in precirrhosis fibrosis were depleted for genes involved in small molecule and drug metabolism, especially butyrylcholinesterase (

BCHE

), a gene involved in the metabolism of drugs of abuse. Differential expression of

BCHE

was validated in the same tissues and cross-sectionally in an expanded cohort of 143 HCV-infected individuals. In a longitudinal study, serum BCHE activity was already decreased at study inception in 19 fibrosis progressors compared with 20 fibrosis nonprogressors (

P

< 0.05). Nonprogressors also had decreased BCHE activity over time compared with initial values, but these evolved a median (range) 8.6 (7.8-11.4) years after the study period inception (

P

< 0.05). Laser captured portal tracts were enriched for immune related genes when compared with hepatocytes but precirrhosis livers lost this enrichment.

Conclusion

: Chronic HCV is associated with hepatocyte

BCHE

loss years before hepatic synthetic function is impaired. These results indicate that

BCHE

may be involved in the pathogenesis of HCV-related fibrosis among injection drug users. (HEPATOLOGY 2012)
INTELLIGENCE AND WORK ADJUSTMENT IN AN NYC POPULATION
Authors: Anderson Wayne , Cox Wray
Published: February 2012

It seems to be generally accepted that disadvantaged persons perform poorly on aptitude tests even when they may have the ability to do a job (Zimpel & Panger, 1970; Seiler, 1970). Other evidence suggests that race is also a factor in poor test performance (Anderson & Smith, 1969; Parker, Kunce, & Bolanovich, 1970). This study is an attempt to see how useful a widely used intelligence test may be for predicting work adjustment of disadvantaged youth when race is considered as a factor.
Spatial orientation mapping of fibers using polarization‐sensitive second harmonic generation microscopy
Authors: Hovhannisyan Vladimir A. , Hu Po‐Sheng , Tan Hsing‐Yuan , Chen Shean‐Jen , Dong Chen‐Yuan
Published: February 2012

In this work, we present a non‐invasive approach to determine azimuth and elevation angles of collagen fibers capable of generating second harmonic signal. The azimuth angle was determined using the minimum of second harmonic generation (SHG) signal while rotating the plane of polarization of excitation light. The elevation angle was estimated from the ratio of the minimal SHG intensity to the intensity when laser polarization and fiber directions were parallel to each other using experimentally determined calibration curve. Pixel‐resolution images of collagen fiber spatial orientation in tendon from bovine leg, chicken leg, and chicken skin were acquired using our approach of SHG polarization‐resolved microscopy. (© 2012 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Oxidative stress markers and apoptosis in the prostate of diabetic rats and the influence of vitamin C treatment
Authors: Gobbo Marina Guimarães , Ribeiro Daniele Lisboa , Taboga Sebastião Roberto , de Almeida Eduardo Alves , Góes Rejane Maira
Published: February 2012

Negative consequences of diabetes on the prostate such as involution are associated with diminished testosterone, insulin deficiency, and hyperglycemia. The contributions of oxidative damage, which usually increases with diabetes, are unknown for these alterations. This study evaluated the impact of streptozotocin‐induced diabetes on the biomarkers of the antioxidant system of rat ventral prostate, the influence of vitamin C supplementation on these biomarkers, and on the balance between cell proliferation and death. Diabetes (D) was induced in Wistar male rats by streptozotocin (5 mg/100 g b.w., i.p.). Control animals (C) were injected with a vehicle. Vitamin C (150 mg/kg b.w./day) supplementation was introduced by gavage in diabetes (D + V) as well as control (C + V) groups. Thirty days after diabetes onset, the rats were killed and the ventral prostates were analyzed using light microscopy, immunocytochemistry, and biochemical assays for biomarkers of oxidative stress. In comparison to control groups, the levels of circulating testosterone, proliferating, and androgen receptor‐positive cells decreased in diabetic groups regardless of vitamin C treatment whereas apoptosis was increased. The levels of superoxide dismutase and glutathione peroxidase did not change, but the levels of glutathione‐S‐transferase (GST) were increased in diabetic prostate. Vitamin C supplementation normalized GST activity and recovered the apoptotic rates in the prostate. In conclusion, GST is a good indicator of compensatory oxidant defense in the prostate at earlier stages of diabetes and vitamin C improves its activity and attenuates apoptosis in the gland. J. Cell. Biochem. 113: 2223–2233, 2012. © 2012 Wiley Periodicals, Inc.
Effects of external electromagnetic fields on the conformational sampling of a short alanine peptide
Authors: Solomentsev Gleb Y. , English Niall J. , Mooney Damian A.
Published: February 2012

Non‐equilibrium molecular dynamics simulations of a solvated 21‐residue polyalanine (A21) peptide, featuring a high propensity for helix formation, have been performed at 300 K and 1 bar in the presence of external electromagnetic (e/m) fields in the microwave region (2.45 GHz) and an r.m.s. electric field intensity range of 0.01–0.05 V/Å. To investigate how the field presence affects transitions between the conformational states of a protein, we report 16 independent 40 ns‐trajectories of A21 starting from both extended and fully folded states. We observe folding‐behavior of the peptide consistent with prior simulation and experimental studies. The peptide displays a natural tendency to form stable elements of secondary structure which are stabilized by tertiary interactions with proximate regions of the peptide. Consistent with our earlier work, the presence of external e/m fields disrupts this behavior, involving a mechanism of localized dipolar alignment which serves to enhance intra‐protein perturbations in hydrogen bonds (English, et al., J. Chem. Phys.
2010, 133, 091105), leading to more frequent transitions between shorter‐lifetime states. © 2012 Wiley Periodicals, Inc.
Stochastic model for photoinduced anisotropy
Authors: Cantatore Valentina , Granucci Giovanni , Persico Maurizio
Published: February 2012

We present a stochastic model for the kinetics of photoinduced anisotropy in a sample of molecular chromophores that may undergo photoisomerization. It is assumed that the chromo‐phores do not interact among them, but are embedded in a medium that slows down the rotational diffusion. The model makes use of data about the photoinduced reorientation of the single chromophore, its photoisomerization and its rotational diffusion, that are made available by molecular dynamics simulations. For the first time such molecular scale processes are computationally connected to the development of anisotropy in a large sample and on a long time scale. A test on azobenzene shows the potentiality of the method and the interplay between photoinduced anisotropy and photoisomerization. © 2012 Wiley Periodicals, Inc.
Knock‐down of plasminogen‐activator inhibitor‐1 enhances expression of E‐cadherin and promotes epithelial differentiation of human pancreatic adenocarcinoma cells
Authors: Lupu‐Meiri Monica , Geras‐Raaka Elizabeth , Lupu Ruth , Shapira Hagit , Sandbank Judith , Segal Liora , Gershengorn Marvin C. , Oron Yoram
Published: February 2012

High levels of plasminogen activator inhibitor‐1 (PAI‐1), which is produced by stromal, endothelial, and cancer cells and has multiple complex effects on cancers, correlate with poor cancer prognosis. To more definitively study the role of endogenously produced PAI‐1 in human pancreatic adenocarcinoma (PAC) PANC‐1 cell line biology, we used anti‐PAI‐1 shRNA to create stable PAI‐1 deficient cells (PD‐PANC‐1s). PD‐PANC‐1s exhibited a heterogeneous morphology. While the majority of cells exhibited a cuboidal shape similar to the parental PANC‐1 or the vector‐infected control cells, numerous large cells with long filopodia and a neuronal‐like appearance were observed. Although both Vector‐control cells and PD‐PANC‐1s expressed mRNAs that are characteristic of mesenchymal, neural, and epithelial phenotypes, epithelial marker RNAs were up‐regulated (e.g., E‐cadherin, 32‐fold) whereas mesenchymal marker RNAs were down‐regulated (e.g., Thy1, ninefold) in PD‐PANC‐1s, suggesting mesenchymal‐to‐epithelial transition. Neural markers exhibited both up‐ and down‐regulation. Immunocytochemistry indicated that epithelial‐like PD‐PANC‐1s expressed E‐cadherin and β‐catenin in significantly more cells, while neural‐like cells exhibited robust expression of organized β‐3‐tubulin. PAI‐1 and E‐cadherin were rarely co‐expressed in the same cells. Indeed, examination of PAI‐1 and E‐cadherin mRNAs expression in additional cell lines yielded clear inverse correlation. Indeed, infection of Colo357 PAC cells (that exhibit high expression of E‐cadherin) with PAI‐1‐expressing adenovirus led to a marked decrease in E‐cadherin expression and to enhanced migration of cells from clusters. Our results suggest that endogenous PAI‐1 suppresses expression of E‐cadherin and differentiation in PAC cells in vitro, supporting its negative impact on tumor prognosis. J. Cell. Physiol. 227: 3621–3628, 2012. © 2012 Wiley Periodicals, Inc.
Glycoxydation promotes vascular damage Via MAPK‐ERK/JNK pathways
Authors: de Nigris Filomena , Rienzo Monica , Sessa Marcella , Infante Teresa , Cesario Elena , Ignarro Louis J. , Al‐Omran Mohammed , Giordano Antonio , Palinski Wulf , Napoli Claudio
Published: February 2012

Oxidation and glycation enhance foam cell formation via MAPK/JNK in euglycemic and diabetic subjects. Here, we investigated the effects of glycated and oxidized LDL (glc‐oxLDL) on MAPK‐ERK and JNK signaling pathways using human coronary smooth muscle cells. Glc‐oxLDL induced a broad cascade of MAPK/JNK‐dependent signaling transduction pathways and the AP‐1 complex. In glc‐oxLDL treated coronary arterioles, tumor necrosis factor (TNF) α increased JNK phosphorylation, whereas protein kinase inhibitor dimethylaminopurine (DMAP) prevented the TNF‐induced increase in JNK phosphorylation. The role of MKK4 and JNK were then investigated in vivo, using apolipoprotein E knockout (ApoE−/−) mice. Peritoneal macrophages, isolated from spontaneously hyperlipidemic but euglycemic mice showed increases in both proteins and phosphorylated proteins. Compared to streptozotocin‐treated diabetic C57BL6 and nondiabetic C57BL6 Wt mice, in streptozotocin‐diabetic ApoE−/− mice, the increment of foam cell formation corresponded to an increment of phosphorylation of JNK1, JNK2, and MMK4. Thus, we provide a first line of evidence that MAPK‐ERK/JNK pathways are involved in vascular damage induced by glycoxidation. J. Cell. Physiol. 227: 3639–3647, 2012. © 2012 Wiley Periodicals, Inc.
Constant and steady transgene expression of interferon‐γ by optimization of plasmid construct for safe and effective interferon‐γ gene therapy
Authors: Ando Mitsuru , Takahashi Yuki , Nishikawa Makiya , Watanabe Yoshihiko , Takakura Yoshinobu
Published: February 2012

Background

Hydrodynamic injection of pmCMVenh‐hEF‐1prom‐muIFN‐γ, a plasmid DNA (pDNA) expressing murine interferon (IFN)‐γ with a murine cytomegalovirus (mCMV) enhancer and a human elongation factor (EF)‐1 promoter, has been proven effective for the treatment of cancer and atopic dermatitis in mice. However, the initial peak of IFN‐γ soon after injection was quite high compared to the steady level for subsequent periods, which could cause unwanted adverse effects. Therefore, in the present study, aiming to optimize the efficacy/side‐effect ratio of IFN‐γ gene transfer, we have developed plasmid vectors encoding murine IFN‐γ under the control of different combinations of promoter and enhancer sequences.

Methods

The promoter and enhancer sequence of pmCMVenh‐hEF‐1prom‐huIFN‐γ, a prototype plasmid expressing human IFN‐γ, was replaced or deleted to obtain various pDNAs. To assess the transgene expression profile, each pDNA was delivered to mice by hydrodynamic injection and the serum IFN‐γ concentration was measured periodically. On the basis of the results obtained, murine IFN‐γ expressing pDNAs were constructed and the body weight change was monitored as an indicator of adverse effects.

Results

The prototype pmCMVenh‐hEF‐1prom‐huIFN‐γ showed a high but declining concentration of IFN‐γ. Those containing hROSA26 promoter expressed the transgene in a more constant manner with no initial high concentrations and scarcely reduced the body weight.

Conclusions

These results indicate that hROSA26 promoter, irrespective of the presence and type of enhancers, is suitable for achieving constant and steady level of transgene expression and effective in avoiding the body weight loss caused by high concentrations of IFN‐γ. Copyright © 2012 John Wiley & Sons, Ltd.
Low b‐value diffusion‐weighted imaging: Emerging applications in the body
Authors: Takahara Taro , Kwee Thomas C.
Published: February 2012

Thanks to recent advances in magnetic resonance imaging technology, it has become possible to perform intravoxel incoherent motion (IVIM) diffusion‐weighted imaging (DWI) in any part of the body. Extracranial applications of DWI are currently under active investigation, especially for oncological imaging. However, the use of non‐quantitative low b‐value (10–100 s/mm2) DWI in the body is still a relatively unexplored field, and its potential is not fully recognized. Non‐quantitative low b‐value DWI may especially be useful for the evaluation of structures that have an inherently low signal at high b‐value DWI, including (but not limited to) the liver, heart, and small bowel. This article will review and discuss the basic principles and potential applications of nonquantitative low b‐value DWI in the body. J. Magn. Reson. Imaging 2012;35:1266–1273. © 2012 Wiley Periodicals, Inc.