bluuebunny/crossref_metadata_2025 huggingface dataset:
Chronic exposure to stress hormones alters the subtype of store‐operated channels expressed in H19‐7 hippocampal neuronal cells
Authors: Piron Matthew , Villereal Mitchel L.
Published: November 2012

Differentiating H19‐7 hippocampal precursor cells up‐regulate (∼4.3‐fold) store‐operated channel (SOC) activity; relatively linear current‐voltage curves indicate an ISOC subtype of SOC. In differentiated H19‐7 neurons, the majority of agonist (arginine vasopressin, AVP)‐stimulated Ca2+ entry occurs via SOCs, based on 2‐aminoethyldiphenylborinate (2‐APB) inhibition data and the observation that transient receptor potential C1 (TRPC1) channel knock down cells show a dramatic reduction of thapsigargin‐stimulated store‐operated Ca2+ entry (SOCE) and inhibition of AVP‐stimulated Ca2+ entry. Treatment of H19‐7 cells with the rat stress hormone corticosterone during differentiation induces a significant increase in AVP‐stimulated Ca2+ entry, which is virtually eliminated by 2‐APB, suggesting a corticosterone‐induced increase of SOCE. Corticosterone also enhances AVP‐stimulated Mn2+ entry, confirming an elevated Ca2+ entry pathway, rather than a decreased Ca2+ extrusion. When corticosterone addition is delayed until after H19‐7 cells have fully differentiated, it still elevates SOCE. In corticosterone‐treated H19‐7 cells, the knock down of TRPC1 no longer blocks thapsigargin‐stimulated Ca2+ entry suggesting that the subtype of SOCs expressed in H19‐7 cells is altered by corticosterone treatment. Electrophysiological studies demonstrate that store‐operated currents in corticosterone‐treated H19‐7 cells exhibit a highly inward rectifying current‐voltage curve consistent with an ICRAC subtype of SOCs. Consistent with this finding is the observation that corticosterone treatment of H19‐7 cells increases the expression of the ICRAC channel subunit Orai1. Thus, the subtype of SOCs expressed in H19‐7 hippocampal neurons can be altered from ISOC to ICRAC by chronic treatment with stress hormones. J. Cell. Physiol. 228: 1332–1343, 2013. © 2012 Wiley Periodicals, Inc.
Prevalence of occult hepatitis C virus infection in Iranian patients with lymphoproliferative disorders
Authors: Farahani Maryam , Bokharaei‐Salim Farah , Ghane Masood , Basi Ali , Meysami Parisa , Keyvani Hossein
Published: November 2012

Occult HCV infection is a form of chronic HCV infection characterized by absence of detectable anti‐HCV antibodies or plasma HCV‐RNA but presence of HCV‐RNA in liver biopsy and/or peripheral blood mononuclear cells (PBMCs). The aim of this study was to determine the presence of HCV‐RNA in PBMCs of patients with lymphoproliferative disorders. One hundred and four consecutive patients with lymphoproliferative disorders admitted to Firouzgar Hospital from January 2010 to March 2011 were recruited in this cross‐sectional study. A 6‐ml sample of whole blood was taken from the patients, the total RNA was extracted from the samples after the separation of plasma and PBMCs. The HCV‐RNA of the samples was amplified by reverse transcriptase‐nested polymerase chain reaction (RT‐nested PCR). The HCV genotypes of the positive samples were tested using the INNO‐LiPA™ HCV II kit, and the HCV genotypes were then confirmed by sequencing of the 5′‐UTR fragments after the PCR products were cloned into a pJET1.2/blunt cloning vector. The mean age of the patients was 48.3 ± 1.76 years (range: 16–83). HCV‐RNA was found in PBMCs from 2 (1.9%) of the 104 patients. Genotyping showed that the patients were infected with HCV subtype 1a. One patient suffered non‐Hodgkin's lymphoma and the other suffered chronic lymphocytic leukemia. Patients with lymphoproliferative disorders with negative anti‐HCV antibodies and negative plasma HCV‐RNA may have occult HCV infection. Therefore, in the absence of a liver biopsy, the testing of PBMCs for the detection of genomic HCV‐RNA may be beneficial. J. Med. Virol. 85:235–240, 2013. © 2012 Wiley Periodicals, Inc.
Serum hepatitis B surface antigen is correlated with intrahepatic total HBV DNA and cccDNA in treatment‐naïve patients with chronic hepatitis B but not in patients with HBV related hepatocellular carcinoma
Authors: Wang Meirong , Qiu Ning , Lu Shichun , Xiu Dianrong , Yu Jianguo , Wang Xing tai , Lu Fengmin , Li Tong , Liu Xueen , Zhuang Hui
Published: November 2012

The aim of the study was to investigate correlations between intrahepatic hepatitis B virus total DNA, covalently closed circular DNA (cccDNA), and serum HBsAg in treatment‐naïve chronic hepatitis B and HBV related hepatocellular carcinoma (HCC). Liver tissues were taken from 42 HBV related HCC and 36 patients with chronic hepatitis B. A fraction of DNA extracted from liver tissue was digested with a plasmid‐safe ATP‐dependent DNase and used for HBV cccDNA detection. The remaining DNA was used for the detection of HBV total DNA and β‐globin, the latter of which is a housekeeping gene and quantified for normalization by real‐time PCR. Quantitation of serum HBsAg was performed by a chemiluminescence assay. Serum HBsAg had positive correlations with serum HBV DNA (r = 0.636, P < 0.001), intrahepatic HBV total DNA (r = 0.519, P = 0.001) and cccDNA (r = 0.733, P < 0.001) in 36 treatment‐naïve chronic hepatitis B, while HBsAg correlated poorly with DNA (r = 0.224, P = 0.210), intrahepatic total DNA and cccDNA in the tumor (r = 0.351, P = 0.031; r = 0.164, P = 0.324, respectively) and non‐tumor (r = 0.237, P = 0.152; r = 0.072, P = 0.667, respectively) liver tissues of 42 HCC. HBV cccDNA and total DNA were significantly higher in liver tissue from chronic hepatitis B than in tumor and non‐tumor of HCC (P < 0.001). Serum HBsAg and HBV DNA were also higher in chronic hepatitis B than in HCC (P < 0.001). It was concluded that levels of serum HBsAg and intrahepatic cccDNA and total DNA were significantly higher in chronic hepatitis B than in HCC, and significant correlations among them were observed in treatment‐naïve chronic hepatitis B but not in HCC. J. Med. Virol. 85:219–227, 2013. © 2012 Wiley Periodicals, Inc.
Effect of processing conditions on the nutritive value of canola meal and presscake. Comparison of the yellow and brown‐seeded canola meal with the brown‐seeded canola presscake
Authors: Theodoridou Katerina , Yu Peiqiang
Published: November 2012

Background

Canola, unlike traditional rapeseed, contains low levels of ‘erucic acid’ and ‘glucosinolates’. Canola's industrial processing generally involves separation of the seed into an oil and a meal fraction whereas the intermediate product is called presscake. The objective of this study was to determine the effect of processing conditions on the nutritive value for ruminants and compare the yellow (Brassica juncea) (CM_Y) and the brown‐seeded (B. napus) (CM_B) canola meal and the brown‐seeded (B. napus) (CPC_B) canola presscake.

Results

Either extract was higher (P < 0.05) for CPC_B than for CM_Y and CM_B. CM_Y had a higher (P < 0.05) PB2 and PC compared to CM_B. Truly digestible fractions, except fatty acid, were lower (P < 0.05) for CPC_B. Effective protein degradability of CM_Y was lower (P < 0.05) compared to CM_B or CPC_B. In vitro protein intestinal digestibility for CM_Y was higher (P < 0.05) than for CM_B or CPC_B.

Conclusion

CPC_B had lower protein but higher oil content than canola meal and is a potential high‐energy supplement source for ruminants. CM_Y had higher crude protein, digestible and metabolizable energy values and low fiber than CM_B. In plant breeding, selection programs are geared towards yellow‐seeded varieties in order to improve the nutritive value of canola meal.© 2012 Society of Chemical Industry
Object‐Based Mapping of Karst Rocky Desertification using a Support Vector Machine
Authors: Xu E.‐Q. , Zhang H.‐Q. , Li M.‐X.
Published: November 2012

Accurate and cost‐effective mapping of karst rocky desertification (KRD) is still a challenge at the regional and national scale. Visual interpretation has been utilised in the majority of studies, while an automated method based on pixel data has been investigated repeatedly. An object‐based method coupling with support vector machine (SVM) was developed and tested using Enhanced Thematic Mapper Plus (ETM+) images from three selected counties (Liujiang, Changshun and Zhenyuan) with different karst landscapes in SW China. The method supports a strategy of defining a mapping unit. It combined ETM+ images and ancillary data including elevation, slope and Normalized Difference Vegetation Index images. A sequence of scale parameters estimation, image segmentation, training data sampling, SVM parameters tuning and object classification was performed to achieve the mapping. A quantitative and semi‐automated approach was used to estimate scale parameters for segmenting an object at an optimal scale. We calculated the sum of area‐weighted standard deviation (WS), rate of change for WS, local variance (LV) and rate of change for LV at each scale level, and the threshold of the aforementioned index that indicated the optimal segment level and merge level. The KRD classification results had overall accuracies of 85·50, 84·00 and 84·86 per cent for Liujiang, Changshun and Zhenyuan, respectively, and kappa coefficients are up to 0·8062, 0·7917 and 0·8083, respectively. This approach mapped six classes of KRD and offered a visually appealing presentation. Moreover, it proposed a conceptual and size‐variable object from the classification standard of KRD. The results demonstrate that the application of our method provides an efficient approach for the mapping of KRD. Copyright © 2012 John Wiley & Sons, Ltd.
Development of Mucoadhesive Drug Delivery System Using Phenylboronic Acid Functionalized Poly(D,L‐lactide)‐b‐Dextran Nanoparticles
Authors: Liu Shengyan , Jones Lyndon , Gu Frank X.
Published: November 2012

Mucoadhesive NP drug carriers have attracted substantial interest as a potential treatment for anterior eye diseases. NPs composed of PLA‐Dex surface functionalized with a mucoadhesive ligand, PBA, were developed as drug carriers with particle sizes ranging from 25 to 28 nm. Using CycA as a model drug, we showed that NPs encapsulated up to 13.7 wt% CycA and exhibited sustained release for up to 5 d in vitro at a clinically relevant dose. We fine‐tuned the PBA density on the NP surface to maximize the mucin‐NP interaction without compromising the particle stability in vitro. This block copolymer conjugate may be useful to improve the bioavailability of topical formulations.

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The R&D Investment–Uncertainty Relationship: Do Strategic Rivalry and Firm Size Matter?
Authors: Czarnitzki Dirk , Toole Andrew A.
Published: November 2012

This paper uses a real options perspective to augment a standard research and development (R&D) investment model and implement a firm‐level empirical analysis to assess the practical significance of market uncertainty and its interactions with strategic rivalry and firm size. We use a measure of firm‐relevant market uncertainty along with panel data and find that firms invest less in current R&D as uncertainty about market returns increases. The effect of firm‐specific uncertainty on R&D investment is smaller in markets where strategic rivalry is likely to be more intense. Furthermore, holding access to financing constant, the effect of uncertainty on R&D investment is attenuated for large firms. Copyright © 2012 John Wiley & Sons, Ltd.
miRNAs, polyphenols, and chronic disease
Authors: Bladé Cinta , Baselga‐Escudero Laura , Salvadó Maria Josepa , Arola‐Arnal Anna
Published: November 2012

MicroRNAs (miRNAs) are small noncoding RNAs, approximately 18–25 nucleotides in length, that modulate gene expression at the posttranscriptional level. Thousands of miRNAs have been described, and it is thought that they regulate some aspects of more than 60% of all human cell transcripts. Several polyphenols have been shown to modulate miRNAs related to metabolic homeostasis and chronic diseases. Polyphenolic modulation of miRNAs is very attractive as a strategy to target numerous cell processes and potentially reduce the risk of chronic disease. Evidence is building that polyphenols can target specific miRNAs, such as miR‐122, but more studies are necessary to discover and validate additional miRNA targets.
Compact ultra‐wideband coplanar waveguide fed fan‐shaped antenna with band‐notched characteristic
Authors: Wang Chen , Yan Ze‐Hong , Xu Ping , Li Sheng
Published: November 2012

In this article, a compact coplanar waveguide fed fan‐shaped monopole antenna for ultra‐wideband applications with band‐notched characteristic is presented. The antenna with fan‐shaped structure occupies a small size of 35 × 30 mm2. An arc‐shaped slot locating on the radiating element is used to create the 3.5 GHz band‐notch characteristic. And, good radiation patterns and gains within the operating band have been observed. © 2012 Wiley Periodicals, Inc. Microwave Opt Technol Lett 55:62–65, 2013; View this article online at wileyonlinelibrary.com. DOI 10.1002/mop.27224
A balanced dual‐resonance colpitts VCO in 0.18 μm CMOS
Authors: Jang Sheng‐Lyang , Chen Yao‐Tsu , Chang Chia‐Wei , Huang Jhin‐Fang
Published: November 2012

A dual‐resonance balanced voltage‐controlled oscillator (VCO) is proposed to serves as a dual‐band oscillator operated at 3.5 and 8.5 GHz. The VCO consists of two single‐ended dual‐resonance LC‐tank complementary Colpitts oscillators configured in a balanced topology. The proposed VCO has been implemented with the TSMC 0.18 μm 1P6M CMOS technology and the core power consumption is 4.21 mW at the supply voltage of 1.2 V. The figure of merit is −190.22/−190.3 dBc/Hz at high/low band. The die area of the dual‐band VCO is 0.995 × 0.55 mm2. © 2012 Wiley Periodicals, Inc. Microwave Opt Technol Lett 55:194–197, 2013; View this article online at wileyonlinelibrary.com. DOI 10.1002/mop.27234
Design and implementation of a UWB six‐port correlator for 6–9 GHz frequency band
Authors: Mohsin Imran , Karlsson Magnus , Owais Owais , Gong Shaofang
Published: November 2012

A compact size six‐port correlator using bandwidth enhancing stubs for the 6–9 GHz ultra wideband radio is presented. The proposed six‐port has a center frequency of 7.5 GHz with 50% relative bandwidth. The correlator is based entirely on microstrip technology for low cost and simple circuit implementation. © 2012 Wiley Periodicals, Inc. Microwave Opt Technol Lett 55:190–193, 2013; View this article online at wileyonlinelibrary.com. DOI 10.1002/mop.27235
Effect of loading a choke‐circuit on the performance of a dual‐band antenna
Authors: Chang The‐Nan , Lin Jyun‐Ming
Published: November 2012

The effect of loading a choke‐circuit on a dual‐band printed inverted‐F antenna is investigated. The choke‐circuit is an LC‐resonator where the inductance is realized by cutting a slot on the ground plane and the capacitance is realized by adding a strip above the ground plane. The total length of the printed circuit board is determined to maximize the return‐loss bandwidth of the lower‐band part of the antenna. By adding the choke‐circuit, the bore‐sight gain within a limited band on the higher‐band part can be increased. The frequency at which there is a maximum bore‐sight gain at the higher‐band part is tunable by the choke‐circuit. © 2012 Wiley Periodicals, Inc. Microwave Opt Technol Lett 55:109–112, 2013; View this article online at wileyonlinelibrary.com. DOI 10.1002/mop.27239
Dual‐polarized band‐stop FSS spatial filters using vicsek fractal geometry
Authors: da Silva M. R. , Nóbrega C. de L. , Silva P. H. da F. , D'Assunção A. G.
Published: November 2012

This article presents a fractal design methodology for frequency selective surfaces (FSSs) by printing a finite planar array of Vicsek fractal metallic patches on a single dielectric layer. Shapes presented by the Vicsek fractal as a function of the fractal parameters (level and scale factor) were exploited to design FSSs acting as dual‐polarized band‐stop spatial filters for incident plane waves. Transmission properties of these FSSs were analyzed and two FSS prototypes were built and measured to validate the fractal design methodology. The obtained results pointing to interesting FSS properties: a high frequency compression factor of 50.31% and stable resonance frequency at oblique incidence. © 2012 Wiley Periodicals, Inc. Microwave Opt Technol Lett 55:31–34, 2013; View this article online at wileyonlinelibrary.com. DOI 10.1002/mop.27242
A miniaturized bandpass filter implemented with substrate integrated coaxial line
Authors: Chu Peng , Hong Wei , Wu Ke , Chen Jixin , Tang Hongjun
Published: November 2012

This article proposed a miniaturized bandpass filter implemented with the substrate integrated coaxial line (SICL).A four‐pole quasi‐elliptic SICL bandpass filter with two symmetric transmission zeros is designed, fabricated, and measured with a minimal size of 0.168 λ0 by 0.088 λ0, where λ0 is the wavelength of free space at the central operating frequency. © 2012 Wiley Periodicals, Inc. Microwave Opt Technol Lett 55:131–133, 2013; View this article online at wileyonlinelibrary.com. DOI 10.1002/mop.27249
Design of compact low‐pass filter with large reject band using open circuit stubs and two‐cascaded DGS quasitriangular resonators
Authors: Challal M. , Boutejdar A. , Azrar A. , Vanhoenacker‐Janvier D.
Published: November 2012

This article investigates a quasitriangular of defected ground structure (DGS) for low‐pass filters (LPFs) application. An equivalent RLC circuit model is presented and its corresponding parameters are as well extracted using the parametric relationships. The LPFs using the proposed DGS pattern combined with open stubs are designed and fabricated. The proposed LPF presents the advantages of small size, low insertion loss and ultrawide stopband with 20 dB attenuation from 4 GHz to >20 GHz. The simulated results obtained by equivalent circuit model and full‐wave electromagnet show good agreement with the measured ones. © 2012 Wiley Periodicals, Inc. Microwave Opt Technol Lett 55:122–127, 2013; View this article online at wileyonlinelibrary.com. DOI 10.1002/mop.27260
Analytical and experimental study of gain enhancement in antenna arrays covered with high index metamaterial superstrate
Authors: Attia Hussein , Siddiqui Omar F. , Suwan Na'el , Ramahi Omar M.
Published: November 2012

Antenna arrays are used in communication applications where directive beams are required.In this article, we show analytically and experimentally that the gain of an antenna array can be further increased by covering it with a high refractive index superstrate. For the experimental demonstration, a corporate‐fed 4 × 1 microstrip patch array is fabricated and the electromagnetic pattern measurements are performed on the array covered with a magneto‐dielectric metamaterial. A fast analytical solution for the radiation fields of the superstrate‐covered microstrip antenna array is also proposed. The analytical solution is based on the reciprocity theorem in conjunction with the transmission line analogy and the cavity model. The artificial superstrate is designed using broadside coupled split ring resonator inclusions and is placed at approximately one‐tenth of a wavelength apart from the patch array operating at 2.2 GHz. A directivity increase of about 3.4 dB is achieved after covering the antenna array with the engineered magnetic superstrate. A comparison of results using the analytical model, the full‐wave simulations and measurements show good agreement. The proposed analytical formulation requires only 2.5% of the time required by full‐wave analysis. The superstrate‐based directivity enhancement method can be used in commercial antennas to combat some of the downsides of the existing systems such as gain decrease due to surface waves and dielectric losses. © 2012 Wiley Periodicals, Inc. Microwave Opt Technol Lett 55:215–218, 2013; View this article online at wileyonlinelibrary.com. DOI 10.1002/mop.27261
Star 16QAM/OOK bidirectional transmission over a TDM‐PON
Authors: Sotiropoulos Nikolaos , Koonen A. M. J. , Waardt Huug de
Published: November 2012

Transmission of Star 16QAM with differential detection has been demonstrated over a time division multiplexing (TDM)‐PON. The multilevel downstream channel is operating at 10 Gb/s, while an OOK signal at 2.5 Gb/s is used for the upstream. Results show very good receiver sensitivity, indicating the modulation format's suitability for next‐generation TDM‐PONs. © 2012 Wiley Periodicals, Inc. Microwave Opt Technol Lett 55:45–47, 2013; View this article online at wileyonlinelibrary.com. DOI 10.1002/mop.27265
Broadband printed planar monople antenna for wireless terminal devices applications
Authors: Sun Jwo‐Shiun , Huang Sheng‐Yi
Published: November 2012

In this study, the compact broadband printed planar monopole antenna is presented for wireless communication devices applications, which is designed to work in 2.4–4.2 and 4.8–5.9 GHz in which it is suitable for Wimax, WLAN, WiFi, and Bluetooth. The ratio of impedance bandwidth of the presented antenna to the central frequency bands of 3.3 and 5.3 GHz is as high as 1.8:1 (BW% = 54.5 and 20.6%, respectively). The total volume of the presented antenna is 45 (L) × 40 (W) × 0.4 (H) mm3, and the antenna gain is 3.0–6.2 dBi in the resonant frequency bands. The experimental results in general agree with the simulated data by high‐frequency structure simulator. © 2012 Wiley Periodicals, Inc. Microwave Opt Technol Lett 55:79–82, 2013; View this article online at wileyonlinelibrary.com. DOI 10.1002/mop.27272
Observation of two N2‐isobutyrylguanine tautomers by NMR spectroscopy
Authors: Yang Lijing , Li Jia , Simionescu Razvan , Yan Hongbin
Published: November 2012

N2‐Isobutyrylguanine was prepared by treatment of guanine with isobutyryl chloride. Two tautomers, 1,7‐dihydro‐2‐(isobutyroyl)amino‐6H‐purin‐6‐one and 1,9‐dihydro‐2‐(isobutyroyl)amino‐6H‐purin‐6‐one, were identified in almost 1 : 1 ratio in dichloromethane–dimethyl sulfoxide (1 : 1 v/v) by NMR spectroscopy. By using the selective‐inversion experiments, enthalpy, entropy, and free energy for activation were determined. This work represents the first report of guanine tautomers observed directly by NMR spectroscopy. Copyright © 2012 John Wiley & Sons, Ltd.
Sacral neuromodulation effects on periurethral sensation and urethral sphincter activity
Authors: Gleason Jonathan L. , Kenton Kimberly , Greer W. Jerod , Ramm Olga , Szychowski Jeff M. , Wilson Tracey , Richter Holly E.
Published: November 2012

Aims

To characterize the effect of sacral neuromodulation (SNM) on urethral neuromuscular function.

Methods

Following IRB approval, women with refractory overactive bladder (OAB) underwent standardized urethral testing prior to and after Stage 1 SNM implantation. Periurethral sensation was measured using current perception thresholds (CPT). Striated urethral sphincter activity was quantified using concentric needle electromyography (CNE) and Multi‐Motor Unit Action Potential (MUP) analysis software. Nonparametric analyses were used to characterize pre/post changes with intervention. Baseline CPT and CNE findings were compared between SNM responders and non‐responders.

Results

Twenty‐seven women were enrolled in this pilot study with a mean age of 61 ± 13 years. Twenty of 26 women (76.9%) responded to SNM and went to Stage 2 permanent implantation. Four (14.8%) withdrew after Stage 1 implantation; three of the four withdrawals had not had therapeutic responses to SNM. CPT and CNE parameters did not significantly differ from baseline 2 weeks after SNM. Pre‐SNM urethral sensation was not significantly different between responders and non‐responders. However, responders had larger amplitude, longer duration and more turns and phases at baseline approaching significance, reflecting more successful urethral reinnervation, than non‐responders.

Conclusions

SNM does not alter urethral neuromuscular function 2 weeks post Stage 1 implantation. Neurourol. Urodynam. 32: 476–479, 2013. © 2012 Wiley Periodicals, Inc.
Self‐adapting protocol tuning for multi‐hop wireless networks using Q‐learning
Authors: Marconett Dan , Lee Minsoo , Ye Xiaohui , Vemuri Rao , Yoo S. J. B.
Published: November 2012

Today's network control systems have very limited ability to adapt to changing network conditions. The addition of reinforcement learning‐based network management agents can improve quality of service by reconfiguring the network layer protocol parameters in response to observed network performance conditions. This paper presents a closed‐loop approach to tuning the layer three protocol based upon current and previous network state observations, specifically the Hello Interval and Active Route Timeout parameters of the AODV routing protocol (AODV‐Q). Simulation results demonstrate that the self‐configuration method proposed here demonstrably improves the performance of the original Ad‐Hoc On‐Demand Distance Vector (AODV) protocol, reducing protocol overhead by 43% and end‐to‐end delay 29% while increasing the packet delivery ratio by up to 11%. Copyright © 2012 John Wiley & Sons, Ltd.
Use of multivariate analysis to suggest a new molecular classification of colorectal cancer
Authors: Domingo Enric , Ramamoorthy Rajarajan , Oukrif Dahmane , Rosmarin Daniel , Presz Michal , Wang Haitao , Pulker Hannah , Lockstone Helen , Hveem Tarjei , Cranston Treena , Danielsen Havard , Novelli Marco , Davidson Brian , Xu Zheng‐Zhou , Molloy Peter , Johnstone Elaine , Holmes Christopher , Midgley Rachel , Kerr David , Sieber Oliver , Tomlinson Ian
Published: November 2012

Molecular classification of colorectal cancer (CRC) is currently based on microsatellite instability (MSI), KRAS or BRAF mutation and, occasionally, chromosomal instability (CIN). Whilst useful, these categories may not fully represent the underlying molecular subgroups. We screened 906 stage II/III CRCs from the VICTOR clinical trial for somatic mutations. Multivariate analyses (logistic regression, clustering, Bayesian networks) identified the primary molecular associations. Positive associations occurred between: CIN and TP53 mutation; MSI and BRAF mutation; and KRAS and PIK3CA mutations. Negative associations occurred between: MSI and CIN; MSI and NRAS mutation; and KRAS mutation, and each of NRAS, TP53 and BRAF mutations. Some complex relationships were elucidated: KRAS and TP53 mutations had both a direct negative association and a weaker, confounding, positive association via TP53–CIN–MSI–BRAF–KRAS. Our results suggested a new molecular classification of CRCs: (1) MSI+ and/or BRAF‐mutant; (2) CIN+ and/or TP53– mutant, with wild‐type KRAS and PIK3CA; (3) KRAS‐ and/or PIK3CA‐mutant, CIN+, TP53‐wild‐type; (4) KRAS– and/or PIK3CA‐mutant, CIN–, TP53‐wild‐type; (5) NRAS‐mutant; (6) no mutations; (7) others. As expected, group 1 cancers were mostly proximal and poorly differentiated, usually occurring in women. Unexpectedly, two different types of CIN+ CRC were found: group 2 cancers were usually distal and occurred in men, whereas group 3 showed neither of these associations but were of higher stage. CIN+ cancers have conventionally been associated with all three of these variables, because they have been tested en masse. Our classification also showed potentially improved prognostic capabilities, with group 3, and possibly group 1, independently predicting disease‐free survival. Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
MYC expression and distribution in normal mature lymphoid cells
Authors: Cattoretti Giorgio
Published: November 2012

The distribution of the product of the proto‐oncogene MYC in lymphoid tissue has not been established in three decades, due to a combination of factors including low abundance, short half‐life, and antibody sensitivity and specificity. We sought to validate antibodies in order to define the expression and distribution of MYC in mature normal lymphoid cells by multiparametric immunophenotyping. Having validated two antibodies for flow cytometry and for immunohistochemistry, we analysed normal tonsil tissue. MYC is expressed predominantly in B cells, some of which are interfollicular large, activated, and cycling CD30+, IRF4+, AID± blasts. Follicular mantle, isotype‐switched memory B cells and FcRH4/IRTA1+ B cells express MYC in a wide range of levels and are small non‐proliferating CDKN1B/p27‐positive or ‐negative resting B lymphocytes. Germinal centre founder cells, CD30+ BCL6± AID± germinal centre blasts, and a population of GC cells in the apical light zone express MYC. MYC is expressed in all phases of the cell cycle in activated and mature B cells, but rarely in other lymphoid types and only partially fulfils the predictions derived from extractive and ex vivo experiments of the past 30 years. Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Correction of first trimester biochemical aneuploidy screening markers for smoking status: influence of gestational age, maternal ethnicity and cigarette dosage
Authors: Spencer Kevin , Cowans Nicholas J.
Published: November 2012

Objective

To examine the gestational age, maternal ethnicity and cigarette dosage effects of the reduction of maternal serum pregnancy‐associated plasma protein A (PAPP‐A) and free‐β human chorionic gonadotrophin (free hCGβ) in smokers.

Methods

Maternal serum PAPP‐A and free hCGβ corrected for confounders, excluding smoking, in first trimester smokers and nonsmokers were compared by gestational age, maternal ethnicity and cigarette dosage. A small set of second trimester smokers and nonsmoker controls were analysed for PAPP‐A along with free hCGβ and assessed for gestational age effects of smoking.

Results

Pregnancy‐associated plasma protein A reduction by smoking in the first trimester was not influenced by gestational age, however free hCGβ levels were only significantly reduced in weeks 12 and 13 in smokers. Ethnicity and cigarette dosage were also found to influence the reduction of both makers in smokers in the first trimester. In second trimester smokers, PAPP‐A was found to be reduced by less and free hCGβ reduced by more than in the first trimester, although no second trimester gestational age effect on smoking was found.

Conclusions

Current methods of correcting for smoking status may be an oversimplification of a more complex subject. © 2012 John Wiley & Sons, Ltd.
Host response to intravenous injection of epsilon toxin in mouse model: A proteomic view
Authors: Kumar Bhoj , Alam Syed Imteyaz , Kumar Om
Published: November 2012

Epsilon toxin (ETX) is an extremely potent pore‐forming toxin and a category B biological agent. ETX is a major virulence determinant of Clostridium perfringens toxinotypes B and D, and is implicated in pathogenesis of rapidly fatal economically important pulpy kidney disease in lambs caused by toxinotype D. Despite being a toxin, ETX can be utilized as a tool to target glutamatergic neurons and for drug delivery into the CNS. 2DE‐MS approach was employed to elucidate the host response to ETX following intravenous injection in mouse model. In total, 136 proteins were identified either differentially expressed in brain (18) and kidney (33); showing specific interaction with ETX from lysates of brain (4), kidney (21), or from plasma (42); and urine markers (18) of intoxication. Differentially expressed proteins in kidney included those involved in calcium homeostasis and cytoskeletal organization. Proteins involved in ER and oxidative stress and energy metabolism also showed differential levels in the target tissue after ETX treatment. The known functions of the proteins differentially expressed and those interacting with ETX indicate involvement of interlinked pathways. This study provides first proteomic account of host response to ETX exposure providing clues to mechanism of toxicity and potential therapeutic targets.
Nasal epithelium biomarkers in young children: Associations with allergic sensitization and environmental stressors
Authors: Sardella Antonia , Voisin Catherine , Dumont Xavier , Marcucci Francesco , Bernard Alfred
Published: November 2012

Background

Recent studies suggest that allergic diseases might have their onset in early epithelial barrier defects. To test this hypothesis, we assessed associations between nasal epithelium biomarkers, environmental stressors, and the risks of allergic sensitization.

Methods

In a cross‐sectional study of 288 kindergarten children (mean age, 5.7 years), we measured aeroallergen‐specific IgE in nasal mucosa and the concentrations of urea, albumin, and Clara cell protein (CC16) in nasal lavage fluid (NALF). Albumin and CC16 in NALF were expressed per liter or as a ratio to urea. We also calculated the NALF CC16/albumin ratio as an index integrating the permeability and the secretory function of the nasal epithelium.

Results

Median NALF concentrations of CC16 and albumin were 8.2 µg/L and 34.5 mg/L, respectively. While there were no significant gender differences when proteins were expressed per liter, the CC16 to albumin and CC16 to urea ratios in NALF were higher in girls than in boys (P = 0.02 and 0.055, respectively. The nasal epithelial barrier function, as reflected by these NALF biomarkers, was positively influenced by probiotics and age, and negatively by environmental stressors such as pool chlorine. The risk of house dust mite (HDM) sensitization increased with decreasing log NALF CC16 concentration, whether expressed per liter (2.59, 95% CI: 1.15–5.82, P = 0.02), as a ratio to urea (1.98, 95% CI: 0.96–4.06, P = 0.06), or as a ratio to albumin (OR, 2.03, 95% CI: 1.10–3.74, P = 0.02). Children in the highest and intermediate tertiles of the NALF albumin/urea ratio were three times more likely to be sensitized to HDM than those in the lowest tertile (both P = 0.04).

Conclusion

Defects in the nasal epithelium barrier function of young children, as reflected by the concentrations of CC16 and albumin in NALF, are associated with environmental factors, including pool chlorine, and with increased risks of HDM sensitization. Pediatr Pulmonol. 2013; 48:571–578. © 2012 Wiley Periodicals, Inc.
Study of the Effect of Covolumes in BKW Equation of State on Detonation Properties of CHNO Explosives
Authors: Suceska Muhamed , Ang How‐Ghee , Serene Chan Hay Yee
Published: November 2012

Due to its simplicity, the Becker‐Kistiakowsky‐Wilson (BKW) equation of state has been used in many thermochemical codes in the calculation of detonation properties. Much work has been done in the calibration of the BKW EOS parameters to achieve agreement with experimental detonation velocities and pressures thus resulting in many different sets of BKW constants (α, β, κ and θ) and covolumes of detonation products, with varying levels of accuracy over broad density limits, i.e. broad pressure limits. The covolumes of the product gases in BKW EOS may be regarded as measures of intermolecular interactions, and their values should affect the predicted detonation properties, particularly at higher explosives densities. This work aims to study the effect of covolumes on calculated values of detonation parameters. Several sets of covolumes available from literature and derived by different methods (matching experimental Hugoniots of individual products, by stochastic optimization, and calculated from van der Waals radii), were studied. In addition, the covolumes of the product gases were also calculated by ab initio methods. The effect of covolumes is studied comparing detonation properties calculated using different sets of covolumes, and experimental data for a series of standard CHNO explosives. It was found that it is possible to reproduce experimental detonation velocities and pressures within reasonable accuracy (root mean square error of less than 5 % for all tested sets) using different set of covolumes, and simultaneously optimizing constants in BKW EOS. However, different values of covolumes strongly affect the composition of detonation products at the Chapman‐Jouguet state. It particularly applies to oxygen‐deficient explosives and at higher densities, where formic acid appears to be an important detonation product.
Evidence from NMR interaction studies challenges the hypothesis of direct lipid transfer from L‐FABP to malaria sporozoite protein UIS3
Authors: Favretto Filippo , Assfalg Michael , Molinari Henriette , D'Onofrio Mariapina
Published: November 2012

UIS3 is a malaria parasite protein essential for liver stage development of Plasmodium species, presumably localized to the membrane of the parasitophorous vacuole formed in infected cells. It has been recently proposed that the soluble domain of UIS3 interacts with the host liver fatty acid binding protein (L‐FABP), providing the parasite with a pathway for importing exogenous lipids required for its rapid growth. This finding may suggest novel strategies for arresting parasite development. In this study, we have investigated the interaction between human L‐FABP and the soluble domain of Plasmodium falciparum UIS3 by NMR spectroscopy. The amino acid residue‐specific analysis of 1H,15N‐2D NMR spectra excluded the occurrence of a direct interaction between L‐FABP (in its unbound and oleate‐loaded forms) and Pf‐UIS3. Furthermore, the spectrum of Pf‐UIS3 was unchanged when oleate or phospholipids were added. The present investigation entails a reformulation of the current model of host‐pathogen lipid transfer, possibly redirecting research for early intervention against malaria.
Microstructure characteristics and shear properties of welding bonding of W/Al dissimilar metals with copper transitional layer
Authors: Chen Jie , Wang Kehong , Zhu Heguo
Published: November 2012

Commercial pure wrought tungsten and 1060 pure aluminum can be joined by using induction‐heat deposition (IHD) welding with commercial pure copper transitional layer. The microstructures of W/Cu/Al interfaces have been studied by means of scanning electron microscope, energy dispersive X‐ray, and X‐ray diffraction. Results show that copper as the transitional metal could form good interfaces with both tungsten and aluminum by IHD under proper processing parameters. The metallic bonding of W/Cu obtained by Cu and W mutual diffusing at a quite limited range without any intermetallic compounds, while eutectic of α(Al)/θ(CuAl2) makes up Cu/Al interface. The average shear strength of W/Cu and Cu/Al interfaces are about 170 MPa and 55 Mpa, respectively, at room temperature. Copyright © 2012 John Wiley & Sons, Ltd.
Oxygen removal from raw silicon powder by the HF‐ethanol solution etching
Authors: Pan Kunming , Zhang Laiqi , Wang Jue , Lin Junpin , Chen Guoliang
Published: November 2012

Silicon powder is vulnerable to oxidation due to its high surface activity. The as‐prepared Si powder is characterized by X‐ray photoelectron spectroscopy spectra coupled with an oxygen nitrogen analyzer, revealing that oxygen impurities mainly consist of Si oxides but with a small amount of free oxygen. The stable oxide films can deteriorate the properties of sintered materials since they cannot be removed during sintering process. The cleaning of these oxides by a single‐HF solution is not straightforward and efficient due to the large surface tension. To remove the oxygen, a more efficient way with the addition of ethanol to a HF solution has been proposed. The addition of a moderate percent of ethanol can decrease the water contact angle and then improve the cleaning efficiency. Importantly, the resulting Si powder possesses good dispersity, uniformity and fluidity. However, excess hydrofluoric acid suppresses oxide removal. Copyright © 2012 John Wiley & Sons, Ltd.
A compact descriptor CHOG3D and its application in human action recognition
Authors: Ji Yanli , Shimada Atsushi , Nagahara Hajime , Taniguchi Rin‐ichiro
Published: November 2012

In this paper, we propose a new method to calculate local features. We extend the FAST corner detector to the spatiotemporal space to extract the shape and motion information of human actions. And a compact peak‐kept histogram of oriented spatiotemporal gradients (CHOG3D) is proposed to calculate local features. CHOG3D is calculated in a small support region of a feature point, and it employs the simplest gradient, the first‐order gradient, for descriptor calculation. Through parameter training, the proper length of the CHOG3D is determined to be 80 elements, which is 1/12.5 times the dimension of HOG3D in the KTH dataset. In addition, it keeps the peak value of quantized gradient to represent human actions more exactly and distinguish them more correctly. CHOG3D overcomes the disadvantages of the complex calculation and huge length of the descriptor HOG3D. From a comparison of the computation cost, CHOG3D is 7.56 times faster than HOG3D in the KTH dataset. We apply the algorithm for human action recognition with support vector machine. The results show that our method outperforms HOG3D and some other currently used algorithms. © 2012 Institute of Electrical Engineers of Japan. Published by John Wiley & Sons, Inc.
Recent trend in risk assessment of formaldehyde exposures from indoor air
Authors: Nielsen Gunnar Damgård , Larsen Søren Thor , Wolkoff Peder
Published: November 2012

Studies about formaldehyde (FA) published since the guideline of 0.1 mg/m3by the World Health Organization (WHO) in 2010 have been evaluated; critical effects were eye and nasal (portal-of-entry) irritation. Also, it was considered to prevent long-term effects, including all types of cancer. The majority of the recent toxicokinetic studies showed no exposure-dependent FA–DNA adducts outside the portal-of-entry area and FA–DNA adducts at distant sites were due to endogenously generated FA. The no-observed-adverse-effect level for sensory irritation was 0.5 ppm and recently reconfirmed in hypo- and hypersensitive individuals. Investigation of the relationship between FA exposure and asthma or other airway effects in children showed no convincing association. In rats, repeated exposures showed no point mutation in thep53andK-Rasgenes at ≤15 ppm neither increased cell proliferation, histopathological changes and changes in gene expression at 0.7 ppm. Repeated controlled exposures (0.5 ppm with peaks at 1 ppm) did not increase micronucleus formation in human buccal cells or nasal tissue (0.7 ppm) or in vivo genotoxicity in peripheral blood lymphocytes (0.7 ppm), but higher occupational exposures were associated with genotoxicity in buccal cells and cultivated peripheral blood lymphocytes. It is still valid that exposures not inducing nasal squamous cell carcinoma in rats will not induce nasopharyngeal cancer or lymphohematopoietic malignancies in humans. Reproductive and developmental toxicity are not considered relevant in the absence of sensory irritation. In conclusion, the WHO guideline has been strengthened.
High-cell-density fermentation and pilot-scale biocatalytic studies of an engineered yeast expressing the heterologous glycoside hydrolase of 7-β-xylosyltaxanes
Authors: Yu Wen-Bo , Liang Xiao , Zhu Ping
Published: November 2012

The glycoside hydrolase of 7-β-xylosyltaxanes (designated as LXYL-P1-2) is encoded by Lxyl-p1-2 isolated from Lentinula edodes. This hydrolase specifically removes C-7 xylose from 7-β-xylosyltaxanes to form 7-β-hydroxyltaxanes, which can be used for the semi-synthesis of paclitaxel or its analogues. In our present study, we established a high-cell-density fermentation of the recombinant Pichia pastoris harboring the Lxyl-p1-2 gene. Moreover, we further optimized the fermentation conditions, including the initial cell density and the dissolved oxygen level in the induction phase. Under optimized conditions, the biomass of 312.3 g/l (wet cell weight, WCW) was obtained, and the biomass activity of the recombinant enzyme reached 6.55 × 104 U/g (WCW). The freeze-dried cells (32 g/l) were used to convert 7-β-xylosyltaxanes (10 g/l, 7-β-xylosyl-10-deacetyltaxol = 62.12 %) in a 5-l reaction volume, and a bioconversion rate about 80 % was achieved. The product purification was performed by ethyl acetate, silica gel chromatography, and preparative HPLC (prep-HPLC), yielding 15.13 g of 10-deacetyltaxol, 3.07 g of 10-deacetylcephalomanine, and 3.47 g of 10-deacetyltaxol C, respectively. In addition, the average recovery rate was around 70 %. Our work provided a foundation for the industrial utilization of the recombinant enzyme on the semi-synthesis of paclitaxel using 7-β-xylosyltaxanes.
Overcoming the Vulnerabilities of the European Economy
Authors: Kremer Christian
Published: November 2012

Regardless of where the financial crisis originated, its effect on European economies stems from internal imbalances, excessive debt and a lack of regulation. The causes and consequences of global economic turmoil have been different in each Member State, but in order for the common currency to survive, European financial institutions will have to be reformed so that they can safeguard us from future shocks even as they strive to overcome current problems. Debt levels are often unsustainable, and fiscal consolidation will have to play a key role in economic policymaking in the future, something that has not been the case in several eurozone countries. The economic union will transfer increasing powers to European institutions in a way that will change economic policymaking in Member States and improve economic convergence between them, but the ultimate objective must always be sustainable and balanced growth for the Union.
The Arab Spring: Finding Common Ground through Values
Authors: Frattini Franco
Published: November 2012

This article provides an overview of the European Union's role following the turmoil in the Arab world, which is causing significant changes to the geopolitical balance of power in the Middle East. The article analyses the refashioned European strategy towards its southern neighbourhood, a strategy aimed at promoting sustainable stability and economic development, deep democracy, high standards in human rights, gender equality, social advancement, religious freedom and intercultural dialogue. There is no real and lasting stability without a true community of values.
Central Europe's Total Legacy
Authors: Granasztéi György
Published: November 2012

The new Central European democracies have in common that they face two legacies of dictatorship. Communism was long-lasting; its legacy is still present. For the centre-right, democratic values and achievements are redefined in light of the Communist legacy.