bluuebunny/crossref_metadata_2025 huggingface dataset:
New Bisaqua Picolinate‐Based Gadolinium Complexes as MRI Contrast Agents with Substantial High‐Field Relaxivities
Authors: Nonat Aline M. , Gateau Christelle , Fries Pascal H. , Helm Lothar , Mazzanti Marinella
Published: January 2012

Two new tripodal heptadentate ligands, H4dpaba (N,N′‐bis[(6‐carboxypyridin‐2‐yl)methyl]aspartic acid) and H3mpatcn(1,4‐bis(methoxycarbonyl)‐7‐[(6‐carboxypyridin‐2‐yl)methyl]‐1,4,7‐triazacyclononane), which bear one or two picolinate pendant arms, have been synthesised. Their lanthanide complexes have been characterised by NMR and fluorescence spectroscopy and potentiometry. Both ligands gave rise to water soluble 1:1 complexes with an increased thermodynamic stability (pGddpaba = 13.3, pGdmpatcn = 11.8, with pGdL = –log [Gd]free at pH 7.4, [Gd]total = 1 μM and [L]total = 10 μM) with respect to the analogous bisaqua complex [Gd(tpaa)(H2O)2] [H3tpaa = α,α′,α″‐nitrilotri(6‐methyl‐2‐pyridinecarboxylic acid), pGdtpaa = 11.2). The two inner‐sphere water molecules confer sizeable relaxivities (r1) to the complexes at high field at physiological pH: r1 = 8.90 and r1 = 7.35 mM–1 s–1 have been measured in HOD at 200 MHz for [Gd(dpaba)(HOD)2]– and [Gd(mpatcn)(HOD)2], respectively. Their relaxometric properties have been investigated by NMRD (Nuclear Magnetic Relaxation Dispersion) and 17O NMR spectroscopy. The formation of ternary complexes with physiological anions, such as acetate, hydrogen carbonate, hydrogen phosphate and citrate, has been monitored by 1H NMR spectroscopy at 200 MHz and pH 7.4. The addition of a large excess (0.6 M) of acetate, hydrogen phosphate and citrate led to the formation monoaqua ternary complexes. Even under these conditions, the average relaxivity remains higher or similar than most currently used contrast agents. Only hydrogen carbonate interacts strongly with the complexes and coordinates in a bidentate mode by displacing both water molecules to induce a twofold decrease in the relaxivity. Both complexes interact with serum albumin to form a macromolecular adduct with increased relaxivity. In particular, a twofold increase of relaxivity has been measured for [Gd(dpaba)(H2O)2]– in bovine serum, which suggests that anion binding does not significantly affect the relaxivity under these conditions.
Diene Dissolution of the Heavier Alkaline Earth Metals
Authors: Michel Olaf , Kaneko Hiroshi , Tsurugi Hayato , Yamamoto Koji , Törnroos Karl W. , Anwander Reiner , Mashima Kazushi
Published: January 2012

Alkaline and alkaline earth metals are efficiently activated in the presence of aromatic hydrocarbons (“potassium–naphthalene”, “magnesium–anthracene”) or (substituted) 1,3‐dienes to produce well‐defined organometallic complexes. In this study, mononuclear diene complexes of calcium, strontium, and barium have been synthesized by utilizing tailor‐made 1,3‐dienes. Complexes [M(2,3‐dimethyl‐1,4‐ditolyl‐1,3‐butadiene)(thf)4] (M = Ca, Sr), [Ca(2,3‐dimethyl‐1,4‐dinaphthyl‐1,3‐butadiene)(thf)4], and {Ba[2,3‐dimethyl‐1,4‐bis(2,4‐dimethylphenyl)‐1,3‐butadiene](thf)4} were isolated and fully characterized including X‐ray structure analyses. Whereas the calcium– and strontium–dienes show an approximate metallacylo‐3‐pentene coordination, barium(II) as the largest nonradioactive metal(II) cation reveals metallacyclo‐2,4‐heptadiene bonding in the solid state. It is further shown that barium(II) can accommodate eight thf molecules as evidenced in the dicationic complex {[Ba(thf)8][B(C6F5)4]2}, obtained from the reaction of barium–diene with trityl borate.
Potentiometric and Voltammetric Study of 6‐Benzylaminopurine and Its Derivatives
Authors: Pilarova Iveta , Lubal Premysl , Trnkova Libuse
Published: January 2012

The protonation‐deprotonation equilibrium of 6‐benzylaminopurine (6‐BAP) and its derivatives was studied by potentiometry and voltammetry. The effect of Cl‐ or OCH3‐group in position 2′, 3′ and 4′ of the benzene ring of 6‐BAP on both pKa values was investigated. To determine the enthalpy and entropy, the temperature dependence of pKa was employed. It was found that with increasing temperature the pKa decreased. In comparison with 6‐BAP the chloro‐ or methoxy‐ group resulted in pKa increase. The first pKa values were also determined by linear sweep (LSV) and elimination voltammetry with linear scan (EVLS). New approaches were shown not only for the determination of pKa from voltammetric titration curves but also for the evaluation of the reduction processes of benzylaminopurines.
Influence of Microwave‐Assisted Pechini Method on La0.80Sr0.20Ga0.83Mg0.17O3–δ Ionic Conductivity
Authors: Boldrini S. , Mortalò C. , Fasolin S. , Agresti F. , Doubova L. , Fabrizio M. , Barison S.
Published: January 2012

With the aim of investigating the microwave influence on the electrolyte material properties, La0.80Sr0.20Ga0.83Mg0.17O2.815 was prepared by both a conventional and a microwave‐assisted sol–gel Pechini method. With respect to the conventional Pechini method (hereafter SGP), the microwave assisted process (hereafter MWA‐SGP) guaranteed a faster procedure, reducing the time needed to remove the excess solvents to complete the polyesterification reaction from some days to a few hours. In fact, when a MWA‐SGP method was used, powders having higher phase purity were obtained. The sintering process at 1,450 °C of the powders prepared by both methods yielded pellets with similar density values (≥92% of theoretical). Nevertheless, only by microwave‐assisted process single‐phase products were obtained and no secondary phases such as tetragonal LaSrGaO4 and LaSrGa3O7 were detected. These by‐products have been demonstrated to be detrimental for conductivity. Indeed, pellets obtained by MWA‐SGP method showed oxygen ionic conductivity values higher (about 30–40%) than those checked for SGP samples, thus demonstrating the important role of the microwave process on reducing time and costs and on improving the electrolyte properties.
Flexural Strength and Viscosity of Glass Ceramic Sealants for Solid Oxide Fuel Cell Stacks
Authors: Malzbender J. , Zhao Y.
Published: January 2012

The structural integrity of the sealing material is critical for the reliability of solid oxide fuel cell stacks. In this respect failure and deformation are aspects which need to be assessed in particular for glass ceramic sealant materials. Bending tests were carried at room temperature and typical stack operation temperature for glass ceramic sealants with different crystallization levels. Elastic moduli, fracture stresses, and viscosity values are reported. In addition to sintered bars some bending testing were carried out for steel specimens that were head‐to‐head joined with the glass ceramics similar as in a stack application. The ceramic particle reinforced sealant material was screen printed onto the steel. The results reveal a decrease of the strength for the partially crystallized sealant at operation relevant temperatures that can be associated with the viscous deformation of the material.
Systematic, morphometric and palaeobiogeographic study of Blainia gregaria Walcott, 1916 (Trilobita, Ptychopariida), Middle Cambrian of the Precordillera of western Argentina
Authors: Bordonaro Osvaldo L. , Pratt Brian R. , Robledo Virginia
Published: January 2012

The ptychoparioid trilobite Blainia gregaria Walcott, 1916 is described for the first time from the late middle Cambrian (Series 3) of the Argentine Precordillera. It occurs commonly in the upper part of La Laja Formation, a carbonate platform succession that crops out in the Precordillera Oriental of San Juan where it reaches a thickness of some 600 m. Sections were sampled on cerro Tres Marías in Sierra de Marquesado and in quebrada de Zonda at the northern termination of Sierra Chica de Zonda. More than 1200 specimens were recovered from 22 stratigraphic levels over a thickness of 155 m, located in the uppermost 15 m of the Soldano Member, the approximately 100 m thick Rivadavia Member, and in the lower 40 m of the Juan Pobre Member. Our biometric study dealt with 205 cranidia and 365 pygidia from cerro Tres Marías. Measured dimensions of a subset of this collection provide bivariate datasets that in some characters show broad scatter plots and relatively low linear correlation coefficients, indicative of rather wide intraspecific morphological variation. Six morphotypes (three cranidial and three pygidial), recognized mainly on the basis of shape, occur together in the same collections. This evidence for an unusually high degree of variability leads to a proposed synonymy of some 30 previously named species in North America belonging to two genera, Blainia Walcott, 1916 and Glyphaspis Poulsen, 1927, the latter considered a junior synonym. The biogeographic distribution of B. gregaria, as redefined here, shows that it was an endemic Laurentian species that inhabited the inner parts of the carbonate platform that rimmed the craton and mantled portions of its interior. Its presence in western Argentina is further evidence for the very close faunal relationship between the Precordilleran terrane, known as Cuyania, and Laurentia during the Cambrian. Copyright © 2012 John Wiley & Sons, Ltd.
Physicochemical studies on glycation‐induced structural changes in human IgG
Authors: Ahmad Saman , Moinuddin  , Khan Rizwan Hasan , Ali Asif
Published: January 2012

Glycation of biomolecules leads to the formation of advanced glycation end products (AGEs). Glycation of immunoglobulin G (IgG) has been implicated in autoimmune diseases such as rheumatoid arthritis (RA). In this study, human IgG was glycated with physiological concentration of glucose. The changes induced in IgG were analyzed by UV, fluorescence, circular dichroism, and Fourier transform infrared (FTIR) spectroscopy; thermal denaturation studies, native, and Sodium dodecyl sulphate (SDS)‐polyacrylamide gel electrophoresis. The ketoamine moieties and carbonyl content were also quantitated in glycated IgG. We report structural perturbations, increased carbonyl content, and ketoamine moieties in the glycated IgG. This may interfere with the normal function of IgG and may contribute to initiation of arthritic complications. AGEs damaged IgG may be used as a biomarker for early detection of RA and the associated secondary complications. © 2012 IUBMB Life, 2012
Measurement of paraben concentrations in human breast tissue at serial locations across the breast from axilla to sternum
Authors: Barr L. , Metaxas G. , Harbach C. A. J. , Savoy L. A. , Darbre P. D.
Published: January 2012

The concentrations of five esters of p‐hydroxybenzoic acid (parabens) were measured using HPLC‐MS/MS at four serial locations across the human breast from axilla to sternum using human breast tissue collected from 40 mastectomies for primary breast cancer in England between 2005 and 2008. One or more paraben esters were quantifiable in 158/160 (99%) of the tissue samples and in 96/160 (60%) all five esters were measured. Variation was notable with respect to individual paraben esters, location within one breast and similar locations in different breasts. Overall median values in nanograms per gram tissue for the 160 tissue samples were highest for n‐propylparaben [16.8 (range 0–2052.7)] and methylparaben [16.6 (range 0–5102.9)]; levels were lower for n‐butylparaben [5.8 (range 0–95.4)], ethylparaben [3.4 (range 0–499.7)] and isobutylparaben 2.1 (range 0–802.9). The overall median value for total paraben was 85.5 ng g−1 tissue (range 0–5134.5). The source of the paraben cannot be identified, but paraben was measured in the 7/40 patients who reported never having used underarm cosmetics in their lifetime. No correlations were found between paraben concentrations and age of patient (37–91 years), length of breast feeding (0–23 months), tumour location or tumour oestrogen receptor content. In view of the disproportionate incidence of breast cancer in the upper outer quadrant, paraben concentrations were compared across the four regions of the breast: n‐propylparaben was found at significantly higher levels in the axilla than mid (P = 0.004 Wilcoxon matched pairs) or medial (P = 0.021 Wilcoxon matched pairs) regions (P = 0.010 Friedman ANOVA). Copyright © 2012 John Wiley & Sons, Ltd.
c-Jun N-terminal kinase 1 negatively regulates osteoblastic differentiation induced by BMP2 via phosphorylation of Runx2 at Ser104
Authors: Huang Yi-Feng , Lin Jing-Jer , Lin Chao-Hsiung , Su Yeu , Hung Shih-Chieh
Published: January 2012

Runx2 plays a crucial role in osteoblastic differentiation, which can be upregulated by bone morphogenetic proteins 2 (BMP2). Mitogen-activated protein kinase (MAPK) cascades, such as extracellular signal-regulated kinase (ERK) and p38, have been reported to be activated by BMP2 to increase Runx2 activity. The role of cjun-N-terminal kinase (JNK), the other kinase of MAPK, in osteoblastic differentiation has not been well elucidated. In this study, we first showed that JNK1 is activated by BMP2 in multipotent C2C12 and preosteoblastic MC3T3-E1 cell lines. We then showed that early and late osteoblastic differentiation, represented by ALP expression and mineralization, respectively, are significantly enhanced by JNK1 loss-of-function, such as treatment of JNK inhibitor, knockdown of JNK1 and ectopic expression of a dominant negative JNK1 (DN-JNK1). Consistently, BMP2-induced osteoblastic differentiation is reduced by JNK1 gain-of-function, such as enforced expression of a constitutively active JNK1 (CA-JNK1). Most importantly, we showed that Runx2 is required for JNK1-mediated inhibition of osteoblastic differentiation, and identified Ser104 of Runx2 is the site phosphorylated by JNK1 upon BMP2 stimulation. Finally, we found that overexpression of the mutant Runx2 (Ser104Ala) stimulates osteoblastic differentiation of C2C12 and MC3T3-E1 cells to the extent similar to that achieved by overexpression of wild-type (WT) Runx2 plus JNK inhibitor treatment. Taken together, these data indicate that JNK1 negatively regulates BMP2-induced osteoblastic differentiation through phosphorylation of Runx2 at Ser104. In addition, unraveling these mechanisms may help to develop new strategies in enhancing osteoblastic differentiation and bone formation. © 2012 American Society for Bone and Mineral Research.
Recent performance improvements to the DFT and TDDFT in GAMESS
Authors: Lasinski Michael E. , Romero Nichols A. , Brown Shawn T. , Blaudeau Jean‐Philippe
Published: January 2012

The general atomic and molecular electronic structure system (GAMESS) is a quantum chemistry package used in the first‐principles modeling of complex molecular systems using density functional theory (DFT) as well as a number of other post‐Hartree‐Fock methods. Both DFT and time‐dependent DFT (TDDFT) are of particular interest to the materials modeling community. Millions of CPU hours per year are expended by GAMESS calculations on high‐performance computing systems; any substantial reduction in the time‐to‐solution for these calculations represents a significant saving in CPU hours. As part of this work, three areas for improvement were identified: (1) the exchange‐correlation (XC) integration grid, (2) profiling and optimization of the DFT code, and (3) TDDFT parallelization. We summarize the work performed in these task areas and present the resulting performance improvement. These software enhancements are available in 12JAN2009R3 or later versions of GAMESS. © 2012 Wiley Periodicals, Inc. J Comput Chem, 2012
Assessment of solid retention time of a temperature phased anaerobic digestion system on performance and final sludge characteristics
Authors: Riau V. , De la Rubia M.A. , Pérez M.
Published: January 2012

BACKGROUND: This paper describes the results obtained during the thermophilic/mesophilic temperature phased anaerobic digestion (TPAD) of sewage sludge on a pilot scale. The aim of this research study was not only to optimize the anaerobic digestion process, but also to obtain a digested sludge suitable for agricultural applications according to the legal requirements.

RESULTS: Four TPAD assays were carried out: 5/15, 3/15, 3/12 and 3/9 (days/days of solid retention time) with a specific methane production (expressed as LCH4 g−1 VSdestroyed) of 0.77, 0.83, 0.66 and 0.20, respectively. TPAD 3/15 and 3/12 reached pathogen concentrations of less than 1000 MPN g−1 TS (faecal colifoms) and 3 MPN per 4 g TS (Salmonella spp.); therefore, these digested sludges can be considered Class A biosolids, according to the US Environmental Protection Agency. Concentrations of heavy metals rose after the anaerobic digestion of mixed sludge, but the final values were always below the limits required by legal regulations.

CONCLUSION: TPAD 3/15 is the best option in terms of organic matter removal, CH4 generation, and process stability. TPAD 3/12 obtained the best final dewaterability and pathogen reduction and in general, showed much better results than those obtained by anaerobic mesophilic control (15 days of SRT). Copyright © 2012 Society of Chemical Industry
H2S biofiltration using expanded schist as packing material: performance evaluation and packed‐bed tortuosity assessment
Authors: Dumont E. , Ayala Guzman L. M. , Rodríguez Susa M. S. , Andrès Y.
Published: January 2012

BACKGROUND: The aim of this work was to test an innovative packing material (expanded schist) for H2S biofiltration in order to determine the packing material performance in terms of elimination capacity, removal efficiency and pressure drop changes. Additionally, the changes over time of bed characteristics, especially tortuosity, were evaluated according to porosity measurements.

RESULTS: Schist material can treat large loading rates (up to 30 g.m−3.h−1) with 100% efficiency at an empty bed residence time (EBRT) of 16 s, which is much better than most results reported in the literature. The porosity of the packed bed is around 40% (tortuosity estimated to range from 1.5 to 2.0) which leads to pressure drop measurements in the range of 10–80 Pa m−1.

CONCLUSION: Schist is a good material for H2S biofiltration in terms of mechanical stability, removal efficiency and effective treatment of high H2S loading rates. Schist is a material that provides the appropriate environment for micro‐organisms by itself. This trend should be confirmed over a long period. Copyright © 2012 Society of Chemical Industry
Study on a carboxyl‐activated carrier and its properties for papain immobilization
Authors: Sun Liwei , Liang Hao , Yuan Qipeng , Wang Tianxin , Zhang Hongchao
Published: January 2012

BACKGROUND: Most enzymes, including protease, play a key role in biotechnology, but their use is quite limited due to poor recovery, limited reusability and instability. Immobilized enzymes offer advantages over free enzymes. This paper reports a simple method for the preparation of immobilized papain, an endolytic cysteine protease (EC: 3.4.22.2), on carboxyl‐activated silica nanoparticles.

RESULTS: The carboxyl‐activated carriers produced reactive carboxyl groups which then react with the free amino groups of enzyme to give peptide bonds (CONH). The results showed that the thermal and pH stabilities of the immobilized papain were higher than those of free enzyme. And the apparent Km value of the immobilized papain was 1.26 times higher than that of free enzyme. Moreover, the immobilized papain retained more than 45% of the original activity after ten reuses continuously.

CONCLUSION: The results indicated that papain was successfully immobilized on the surface of the activated carriers. The immobilized papain had not only higher activity recovery, but also better stability, reusability and environmental adaptability. Copyright © 2012 Society of Chemical Industry
Efficient synthesis of pyrimido[5,4‐c]pyridazines and of thiino[2,3‐d]pyrimidines based on an aza‐wittig reaction/heterocyclization strategy
Authors: Barsy Magda A. , El Rady Eman A. , Ismael Mostafa A.
Published: January 2012

A simple one‐pot and efficient method is described for the synthesis of pyrimido[5,4‐c]pyridazines 5 and of thiino[2,3‐d] pyrimidines 15 by a domino process involving an aza‐Wittig reaction/heterocyclization. The iminophosphorane 2 reacted with phenylisocyanate, followed by heterocyclization on addition of amines to give the corresponding guanidine intermediates 4. The guanidine intermediates were cyclized in the presence of catalytic amount of sodium ethoxide to pyrimido[5,4‐c]pyridazines 5. Similarly, iminophosphorane 12 reacted with phenylisocyanate and amines to give thiino[2,3‐d]pyrimidines 15 in moderate yields. Furthermore, pyridazino[4,3‐d]oxazines 10 and thiino[2,3‐d]oxazines 19 were synthesized by the intremolecular aza‐Wittig reaction of phosphazenes 2 and 12, respectively, with acid chlorides followed by heterocylization via imidoyl chloride intermediates. J. Heterocyclic Chem., (2012).
Evaluation of lymph node metastases: Comparison of gadofluorine M‐enhanced MRI and diffusion‐weighted MRI in a rabbit VX2 rectal cancer model
Authors: Kim Seung Ho , Lee Jeong Min , Moon Sung Kyoung , Chung Yong Eun , Paik Jin Ho , Choi Seung Hong , Kim Min Uk , Han Joon Koo , Choi Byung Ihn
Published: January 2012

Purpose:

To compare the diagnostic performance of a diffusion‐weighted imaging (DWI) dataset and a gadofluorine M‐enhanced imaging dataset for identifying lymph node (LN) metastases in a rabbit rectal cancer model.

Materials and Methods:

VX2 carcinomas were injected into the rectum of 26 rabbits. Four weeks later, T2‐weighted imaging (T2WI), pre‐T1WI, DWI, and post‐T1WI were performed. Two radiologists independently reviewed the DWI set (T2WI, pre‐T1WI, DWI) and the gadofluorine M set (T2WI, pre‐ and post‐T1WI) and recorded their confidence scores for LN metastasis on a per‐LN basis. Receiver operating characteristic (ROC) analysis was performed to compare the area under the ROC curve (Az) of the two imaging sets. Histopathologic results were used as the reference standard.

Results:

The Az and sensitivity of the gadofluorine M set were comparable to those of the DWI set (Az, for reader 1, 0.849, 0.829, P = 0.571; for reader 2, 0.923, 0.876, P = 0.212; sensitivity, for reader 1, 97%, 97%; for reader 2, 97%, 92%, P = 0.304). The specificity of the former was greater than that of the latter (for reader 1, 65%, 53%, P = 0.0003; for reader 2, 81%, 68%, P = 0.01).

Conclusion:

Gadofluorine M‐enhanced images provided greater specificity than DWI for identifying LN metastases, whereas the Az and sensitivity of the former were comparable to those of the latter. J. Magn. Reson. Imaging 2012;35:1179‐1186. © 2012 Wiley Periodicals, Inc.
Detection and classification of contrast‐enhancing masses by a fully automatic computer‐assisted diagnosis system for breast MRI
Authors: Renz Diane M. , Böttcher Joachim , Diekmann Felix , Poellinger Alexander , Maurer Martin H. , Pfeil Alexander , Streitparth Florian , Collettini Federico , Bick Ulrich , Hamm Bernd , Fallenberg Eva M.
Published: January 2012

Purpose:

To evaluate a fully automatic computer‐assisted diagnosis (CAD) method for breast magnetic resonance imaging (MRI), which considered dynamic as well as morphologic parameters and linked those to descriptions laid down in the Breast Imaging Reporting and Data System (BI‐RADS) MRI atlas.

Materials and Methods:

MR images of 108 patients with 141 histologically proven mass‐like lesions (88 malignant, 53 benign) were included. The CAD system automatically performed the following processing steps: 3D nonrigid motion correction, detection of lesions by a segmentation algorithm, extraction of multiple dynamic and morphologic parameters, and classification of lesions. As one final result, the lesions were categorized by defining their probability of malignancy; this so‐called morpho‐dynamic index (MDI) ranged from 0%–100%. The results of the CAD system were correlated with histopathologic findings.

Results:

The CAD system had a high detection rate of the histologically proven lesions, missing only two malignancies of invasive multifocal carcinomas and four benign lesions (three fibroadenomas, one atypical ductal hyperplasia). The 86 detected malignant lesions showed a mean MDI of 86.1% (±15.4%); the mean MDI of the 49 coded benign lesions was 41.8% (±22.0%; P < 0.001). Based on receiver‐operating characteristic analysis, the diagnostic accuracy of the CAD system was 93.5%. Using an appropriate cutoff value (MDI 50%), sensitivity was 96.5% combined with specificity of 75.5%.

Conclusion:

The fully automatic CAD technique seems to reliably distinguish between benign and malignant mass‐like breast tumors. Observer‐independent CAD may be a promising additional tool for the interpretation of breast MRI in the clinical routine. J. Magn. Reson. Imaging 2012;35:1077‐1088. © 2011 Wiley Periodicals, Inc.
Viral load and epidemiological profile of patients infected by pandemic influenza a (H1N1) 2009 and seasonal influenza a virus in Southern Brazil
Authors: Gorini da Veiga Ana Beatriz , Kretzmann Nélson Alexandre , Corrêa Laura Trevizan , Goshiyama Alessandra Mari , Baccin Tatiana , Ardenghi Patrícia , Matias Fernanda , Gregianini Tatiana Schaffer , Alves d'Azevedo Pedro
Published: January 2012

Correlation between virologic profile and clinical features of patients infected by influenza virus provides important information for epidemiological control and clinical management of future disease outbreaks. Samples from patients in Southern Brazil, from June to December 2009, were examined and the viral load was correlated with epidemiological data. All samples were analyzed by qRT‐PCR for detection of the 2009‐pandemic Influenza A (H1N1). Relative viral loads were assessed based on the 2−ΔCT method and epidemiological data were obtained for each patient, following ethical policies. A total of 933 samples were positive for pH1N1 (2009) influenza; 172 were positive for seasonal influenza A; 13 were undetermined; 1992 samples were negative for influenza A. Combined molecular and epidemiological data were available for 38 seasonal and 198 pandemic samples. The median viral load was higher in pandemic than in seasonal influenza samples; in patients infected with pH1N1 (2009), viral load associated positively with chills, myalgia and rhinorrhea, and negatively with dyspnea, but no association was observed with other symptoms, nor with clinical conditions such as pregnancy, smoking, immunodepression and co‐morbidities. Regarding patients infected with seasonal influenza, viral loads did not show statistically significant association with any of the symptoms. This is the first study in Brazil that examines epidemiological and molecular data from the 2009 influenza pandemic. The results may serve as a basis for developing strategies to control human‐to‐human infection and viral dissemination, and for implementing effective measures and public health policies against future novel disease outbreaks. J. Med. Virol. 84:371–379, 2012. © 2011 Wiley Periodicals, Inc.
Case report: Increased viral receptor expression associated with high viral load and severe pneumonia in a young patient infected with 2009 H1N1 influenza a with no pre‐existing conditions
Authors: Boonarkart Chompunuch , Champunot Ratapum , Uiprasertkul Mongkol , Bunthi Charatdao , Kiatboobsri Sumalee , Rochanawutanon Mana , Porncharoenpong Suchat , Suptawiwat Ornpreya , Auewarakul Prasert
Published: January 2012

A case of unusually high severity of influenza pneumonia leading to acute respiratory distress syndrome and death was investigated. This was a previously a healthy 28‐year‐old man with no underlying conditions, admitted to a hospital during the first wave of influenza pandemic in Thailand in July 2009. He had experienced high fever and influenza‐like illness for 5 days before coming to the hospital. He developed acute respiratory distress syndrome and expired on day 7 after admission. In comparison to three other cases of influenza pneumonia in the same outbreak with known risk factors for severe influenza, such as pregnancy and diabetes mellitus, a much higher viral load was detected in the lungs of this patient despite antiviral treatment. In agreement with the high viral load, the lung specimens from this patient, but not the other three patients, showed a high expression of α‐2,6‐linked sialic acid by lectin staining. The gene responsible for the synthesis of this sialic acid was also found to be upregulated. The data indicated overexpression of the viral receptor as a potential mechanism for severe disease in some patients. J. Med. Virol. 84:380–385, 2012. © 2011 Wiley Periodicals, Inc.
An in‐house HIV genotyping assay for the detection of drug resistance mutations in Southeast Asian patients infected with HIV‐1
Authors: Lee Chun Kiat , Lee Hong Kai , Loh Tze Ping , Sethi Sunil Kumar , Koay Evelyn Siew‐Chuan , Tang Julian Wei‐Tze
Published: January 2012

Genotyping for HIV drug resistance is costly and beyond the means for many Southeast Asian patients, who are self‐funded. This prompted the development of a more cost‐effective, in‐house assay for an ethnically diverse, Southeast Asian population at the National University Hospital in Singapore, using Sanger‐based sequencing. Plasma samples from 20 treatment‐failure patients with a broad spectrum of HIV drug resistance mutations were used to validate this assay clinically. Blinded testing gave concordant results for 7/7 (100%) protease drug resistance‐related mutations, including one major and six minor mutations, and 111/116 (95.7%) reverse‐transcriptase (RT) drug resistance‐related mutations, including 65 nucleoside RT inhibitors (NRTI) and 46 non‐nucleoside RT inhibitors (NNRTI) mutations. There were five discordant results, involving three NRTI‐ and two NNRTI‐resistance‐associated mutations. Highly conserved primers designed to have a wide coverage of the HIV pol gene (covering the entire protease and 395 codons of the RT region) enabled efficient multi‐ethnic population‐based genotyping. Reagents for this in‐house test cost around 60% less than those for commercially available assays (SGD150 vs. SGD350 per sample). In addition, this assay also identified mutations located within the C‐terminal domain (codons 312–560) of RT that are beyond the reach of most published and commercial GRTs. Currently, most research on C‐terminal drug‐resistance‐related mutations has been conducted on HIV subtype B infections. Therefore this assay enables further study of these C‐terminal mutations in Southeast Asian populations, where there is a high prevalence of CRF01_AE and other non‐subtype B HIV infections. J. Med. Virol. 84:394–401, 2012. © 2011 Wiley Periodicals, Inc.
Prevalence of hepatitis C virus genotype 1a in Japan and correlation of mutations in the NS5A region and single‐nucleotide polymorphism of interleukin‐28B with the response to combination therapy with pegylated‐interferon‐alpha 2b and ribavirin
Authors: Hayashi Kazuhiko , Katano Yoshiaki , Kuzuya Teiji , Tachi Yoshihiko , Honda Takashi , Ishigami Masatoshi , Itoh Akihiro , Hirooka Yoshiki , Ishikawa Tetsuya , Nakano Isao , Urano Fumihiro , Yoshioka Kentaro , Toyoda Hidenori , Kumada Takashi , Goto Hidemi
Published: January 2012

Hepatitis C virus (HCV) genotype 1a is rare in Japanese patients and the clinical characteristics of this genotype remain unclear. The interferon (IFN) sensitivity‐determining region (ISDR) and single‐nucleotide polymorphisms (SNPs) of interleukin‐28B (IL28B) among patients with HCV genotype 1b are associated with IFN response, but associations among patients with genotype 1a are largely unknown. This study investigated the clinical characteristics of genotype 1a and examined whether genomic heterogeneity of the ISDR and SNPs of IL28B among patients with HCV genotype 1a affects response to combination therapy with pegylated‐IFN‐α2b and ribavirin. Subjects comprised 977 patients infected with HCV genotype 1, including 574 men and 412 women (mean age, 55.2 ± 10.6 years). HCV was genotyped by direct sequencing of the 5′‐untranslated region and/or core regions and confirmed by direct sequencing of the NS5A region. HCV genotypes 1a (n = 32) and 1b (n = 945) were detected. Twenty‐three (71.9%) of the 32 patients with genotype 1a were patients with hemophilia who had received imported clotting factors. Prevalence of genotype 1a after excluding patients with hemophilia was thus 0.9%. Of the 23 patients with genotype 1a who completed IFN therapy, 11 (47.8%) were defined as achieving sustained virological response. Factors related to sustained virological response by univariate analysis were IL28B and ISDR. In conclusion, HCV genotype 1a is rare in Japan. The presence of IL28B genotype TT, and more than two mutations, in the ISDR are associated with a good response to IFN therapy in patients with HCV genotype 1a. J. Med. Virol. 84:438–444, 2012. © 2011 Wiley Periodicals, Inc.
Human metapneumovirus‐associated hospital admissions over five consecutive epidemic seasons: Evidence for alternating circulation of different genotypes
Authors: Apostoli Paola , Zicari Sonia , Presti Alessandra Lo , Ciccozzi Massimo , Ciotti Marco , Caruso Arnaldo , Fiorentini Simona
Published: January 2012

Human metapneumovirus (hMPV) is a pathogen of the respiratory tract with a worldwide distribution. The purpose of this study was to identify hMPV as the cause of acute respiratory diseases in children admitted at Spedali Civili, a public hospital in Brescia, Italy. Eight hundred forty‐six nasopharyngeal aspirate samples negative for the presence of other common respiratory viruses were tested for the presence of hMPV RNA by reverse transcription‐polymerase chain reaction. Of the 846 samples, 79 (9.3%) were positive for hMPV. Polymerase chain reaction products, obtained by amplification of the partial nucleotide sequence of gene F, were sequenced and compared with sequences deposited in GenBank. All four hMPV subtypes were identified, including the proposed subtype A2 sublineages “A” and “B”. In successive epidemic seasons, large outbreaks of hMPV alternated with small outbreaks in a biannual pattern. This local study provides further evidence that hMPV infection should be considered as a reason for hospital admission for acute respiratory disease in children. J. Med. Virol. 84:511–516, 2012. © 2011 Wiley Periodicals, Inc.
The 40–80 nt region in the 5′‐NCR of genome is a critical target for inactivating poliovirus by chlorine dioxide
Authors: Jin Min , Zhao Zu‐Guo , Wang Xin‐Wei , Shen Zhi‐Qiang , Xu Lu , Yu Yun‐Mei , Qiu Zhi‐Gang , Chen Zhao‐Li , Wang Jing‐Feng , Huang Ai‐Hua , Li Jun‐Wen
Published: January 2012

Chemical disinfection is the most common method used to inactivate viruses from drinking water throughout the world. In this study, cell culture, ELISA, RT‐PCR, and spot hybridization were employed to investigate the mechanism underlying chlorine dioxide (ClO2)‐induced inactivation of Poliovirus type 1 (PV1), which was also confirmed by recombinant viral genome RNA infection models. The results suggested that ClO2 inactivated PV1 primarily by disrupting the 5′‐non‐coding region (5′‐NCR) of the PV1 genome. Further study revealed that ClO2 degraded specifically the 40–80 nucleotides (nt) region in the 5′‐NCR. Recombinant viral genome RNA infection models confirmed that PV1 RNA lacking this 40–80 nt region was not infectious. This study not only elucidated the mechanism of PV1 inactivation by ClO2, but also defined the critical genetic target for the disinfectant to inactivate Poliovirus. This study also provides a strategy by which rapid, accurate, and molecular methods based on sensitive genetic targets may be established for evaluating the effects of disinfectants on viruses. J. Med. Virol. 84:526–535, 2012. © 2011 Wiley Periodicals, Inc.
Single treatment with ethanol hand rub is ineffective against human rhinovirus—hand washing with soap and water removes the virus efficiently
Authors: Savolainen‐Kopra Carita , Korpela Terttu , Simonen‐Tikka Marja‐Leena , Amiryousefi Ali , Ziegler Thedi , Roivainen Merja , Hovi Tapani
Published: January 2012

Ethanol‐containing hand rubs are used frequently as a substitute for hand washing with water and soap. However, not all viruses are inactivated by a short term rubbing with alcohol. The capacity of a single round of instructed and controlled hand cleaning with water and soap or ethanol‐containing hand rub, respectively, was tested for removal of human rhinovirus administered onto the skin of healthy volunteers on the back of the hands. Hand washing with soap and water appeared to be much more efficient for removing rhinoviruses from skin than rubbing hands with an ethanol‐containing disinfectant. After washing with soap and water the virus was detected in 3/9 (33.3%) test persons from the left hand and 1/9 (11.1%) cases from the right hand, whereas the virus was detected invariably by real‐time RT‐PCR from both hands after cleaning with alcohol hand rub (P‐value <0.01). Both substances evaluated clinically were also tested in vitro for virucidal efficacy against Human rhinovirus2 (HRV2) using a standardized assay. Both tested substances were poor within the contact time used in the hand‐cleaning test. In conclusion, thorough and conventional hand washing with water and soap can clean efficiently hands contaminated with the virus responsible for an extensive share of common cold episodes. J. Med. Virol. 84:543–547, 2012. © 2011 Wiley Periodicals, Inc.
Case report: Benefits of quantitative polymerase chain reaction in the clinical management of herpes simplex virus 1 infection with prominent hepatitis and unusual secondary progression
Authors: Chaillon Antoine , Schnepf Nathalie , Jonas Maud , Mondon Karl , Orain Isabelle , Lioger Bertrand , Cottier Jean‐Philippe , Hommet Caroline , Goudeau Alain
Published: January 2012

Herpes simplex virus (HSV) infection is rarely considered in the differential diagnosis of severe acute hepatitis and disseminated infection in immunocompetent adults. A case of disseminated HSV‐1 infection in an 82‐year‐old woman initially presenting with neurological problems, signs of meningitis and prominent hepatitis was investigated. Initial diagnosis, monitoring, and follow‐up were based on the application of molecular methods to cerebrospinal fluid, serum, and liver tissue samples from this patient. Following an initial full recovery, the patient presented delayed intracerebral haemorrhage and diffuse arthralgia. This atypical case, with delayed secondary progression, highlights the wide range of clinical features of HSV infection and the benefits of monitoring viral load by quantitative real‐time polymerase chain reaction (PCR) during patient management. J. Med. Virol. 84:457–461, 2012. © 2011 Wiley Periodicals, Inc.
A longitudinal study of mentor and protégé outcomes in formal mentoring relationships
Authors: Chun Jae Uk , Sosik John J. , Yun Nam Yi
Published: January 2012

This study examined relationships between mentoring functions offered and transformational leadership as a mentor outcome and affective well‐being and organizational commitment as mutual outcomes for both mentors and protégés. For this examination, we conducted a longitudinal field study by using 111 matched reports from both mentors and protégés collected at three different points in time over seven months in nine Korean companies that administered a standardized formal mentoring program. Study results showed that mentoring functions assessed at Time 2 were positively associated with mentors' and protégés' post‐mentoring outcomes at Time 3 after controlling for pre‐mentoring initial levels of those outcomes at Time 1. Study findings also revealed that relative effects of mentoring on the mentor and protégé outcomes differed by the types of mentoring functions. We discuss the theoretical, practical, and methodological implications from these results. Copyright © 2012 John Wiley & Sons, Ltd.
Negative effects of ADAMTS‐7 and ADAMTS‐12 on endplate cartilage differentiation
Authors: Zhang Qiang , Huang Ming , Wang Xiaolin , Xu Xiaojie , Ni Ming , Wang Yan
Published: January 2012

The roles of ADAMTS‐7 and ADAMTS‐12 in disc degeneration have not been previously examined. The purpose of this study was to examine the expression of ADAMTS‐7 and ADAMTS‐12 in the endplate cells isolated from patients with degenerative disc disease and to see whether they are associated with the pathological change of endplate. Sixty‐four degenerated lumbar endplate specimens were obtained from the patients with degenerative disc disease categorized as type Modic I or II in magnetic resonance imaging (MRI) and 12 nondegenerative specimens as control (vertebra burst fracture patients without degenerative change in MRI) during surgical procedures. The expression of ADAMTS‐7 and ADAMTS‐12 was examined by real‐time PCR and Western blotting. A statistically significant increase in mRNA expression of ADAMTS‐7 and ADAMTS‐12 was observed in the endplate cells in degenerative discs compared with nondegenerative discs. The corresponding protein levels of ADAMTS‐7 and ADAMTS‐12 had the same expression patterns. Moreover, ADAMTS‐7 and ADAMTS‐12 down‐regulated the expression of Col II, Sox9, and Col X the marker genes for chondrogenesis. Our results indicate that ADAMTS‐7 and ADAMTS‐12 appear to be potent negative regulators of endplate cartilage development. © 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 30:1238–1243, 2012
Fracture healing in protease‐activated receptor‐2 deficient mice
Authors: O'Neill Kevin R. , Stutz Christopher M. , Mignemi Nicholas A. , Cole Heather , Murry Matthew R. , Nyman Jeffry S. , Hamm Heidi , Schoenecker Jonathan G.
Published: January 2012

Protease‐activated receptor‐2 (PAR‐2) provides an important link between extracellular proteases and the cellular initiation of inflammatory responses. The effect of PAR‐2 on fracture healing is unknown. This study investigates the in vivo effect of PAR‐2 deletion on fracture healing by assessing differences between wild‐type (PAR‐2+/+) and knock‐out (PAR‐2−/−) mice. Unilateral mid‐shaft femur fractures were created in 34 PAR‐2+/+ and 28 PAR‐2−/− mice after intramedullary fixation. Histologic assessments were made at 1, 2, and 4 weeks post‐fracture (wpf), and radiographic (plain radiographs, micro‐computed tomography (µCT)) and biomechanical (torsion testing) assessments were made at 7 and 10 wpf. Both the fractured and un‐fractured contralateral femur specimens were evaluated. Polar moment of inertia (pMOI), tissue mineral density (TMD), bone volume fraction (BV/TV) were determined from µCT images, and callus diameter was determined from plain radiographs. Statistically significant differences in callus morphology as assessed by µCT were found between PAR‐2−/− and PAR‐2+/+ mice at both 7 and 10 wpf. However, no significant histologic, plain radiographic, or biomechanical differences were found between the genotypes. The loss of PAR‐2 was found to alter callus morphology as assessed by µCT but was not found to otherwise effect fracture healing in young mice. © 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 30:1271–1276, 2012
Hypocholesterolaemic and antioxidant activities of chickpea (Cicer arietinum L.) protein hydrolysates
Authors: Yust María del Mar , Millán‐Linares María del Carmen , Alcaide‐Hidalgo Juan María , Millán Francisco , Pedroche Justo
Published: January 2012

BACKGROUND: Some dietary proteins possess biological properties which make them potential ingredients of functional or health‐promoting foods. Many of these properties are attributed to bioactive peptides that can be released by controlled hydrolysis using exogenous proteases. The aim of this work was to test the improvement of hypocholesterolaemic and antioxidant activities of chickpea protein isolate by means of hydrolysis with alcalase and flavourzyme.

RESULTS: All hydrolysates tested exhibited better hypocholesterolaemic activity when compared with chickpea protein isolate. The highest cholesterol micellar solubility inhibition (50%) was found after 60 min of treatment with alcalase followed by 30 min of hydrolysis with flavourzyme. To test antioxidant activity of chickpea proteins three methods were used: β‐carotene bleaching method, reducing power and 2,2‐diphenyl‐1‐picrylhydrazyl (DPPH) radical‐scavenging effect since antioxidant activity of protein hydrolysates may not be attributed to a single mechanism. Chickpea hydrolysates showed better antioxidant activity in all assays, especially reducing power and DPPH scavenging effect than chickpea protein isolate.

CONCLUSION: The results of this study showed the good potential of chickpea protein hydrolysates as bioactive ingredients. The highest bioactive properties could be obtained by selecting the type of proteases and the hydrolysis time. Copyright © 2012 Society of Chemical Industry
Length of Stay: Price and Income Semi‐Elasticities at Different Destinations in Italy
Authors: Salmasi Luca , Celidoni Martina , Procidano Isabella
Published: January 2012

In this paper, we estimate price and income semi‐elasticities of the length of stay at different destinations in Italy using the ‘Multipurpose survey on tourism demand, holidays and trips’ provided by the Italian National Institute of Statistics (ISTAT). We derive the conditional demand function for the length of stay, which depends on tourists' socio‐demographic characteristics, travel characteristics, income and price of touristic services. Since income was not reported in our database, we use the propensity score matching to retrieve this information from the ‘Survey on household income and wealth (SHIW)’, and we use quantile regression to account for the multimodality of the length of stay. Copyright © 2012 John Wiley & Sons, Ltd.
Immunosuppression induction with rabbit anti-thymocyte globulin with or without rituximab in 1000 liver transplant patients with long-term follow-up
Authors: Mangus Richard S. , Fridell Jonathan A. , Vianna Rodrigo M. , Kwo Paul Y. , Chen Jeanne , Tector Joseph A.
Published: January 2012

Rabbit anti-thymocyte globulin (rATG)–based immunosuppression induction is being increasingly used in liver transplantation (LT) in conjunction with steroid-free protocols to delay the initiation of calcineurin inhibitors. This study reports a single-center comparison of transplant outcomes and complications in 3 immunosuppression eras. Data were obtained retrospectively from a center research database, and the analysis included LT patients from 2001 to 2008. The immunosuppression consisted of rATG induction in 3 doses (6 mg/kg in all): (1) the first dose was administered perioperatively [the rabbit anti-thymocyte globulin in the operating room (rATG-OR) era]; (2) the first dose was delayed until 48 hours after transplantation [the rabbit anti-thymocyte globulin after a delay (rATG-D) era]; or (3) the first dose was delayed until 48 hours after transplantation, and a single dose of rituximab was added 72 hours after transplantation [the rabbit anti-thymocyte globulin after a delay plus rituximab (rATG-D-Ritux) era]. The initial maintenance immunosuppression was tacrolimus monotherapy, which was started on postoperative day 2. There were 166 patients (16%) in the rATG-OR era, 259 patients (26%) in the rATG-D era, and 588 patients (58%) in the rATG-D-Ritux era (1013 patients in all). Demographically, the latter eras were characterized by higher recipient and donor ages; greater percentages of liver-kidney transplants, hepatocellular carcinoma (HCC), donation after cardiac death (DCD), and imported organs; and shorter graft ischemia times. There were no significant differences between the 3 immunosuppression groups in unadjusted patient survival 3 and 5 years after transplantation (80% and 75% for the rATG-OR era, 75% and 67% for the rATG-D era, and 79% and 71% for the rATG-D-Ritux era, P = 0.15). The 5-year survival rates for patients with hepatitis C virus (HCV) and HCC were 65% and 68%, respectively. The factors included in the Cox regression model for patient death included the Model for End-Stage Liver Disease score [hazard ratio (HR) = 1.03, P = 0.001], HCV (HR = 1.28, P = 0.04), donor age (HR = 1.01, P = 0.001), recipient age (HR = 1.01, P = 0.05), and DCD (HR = 1.55, P = 0.11). rATG-based induction immunosuppression can be safely used in adult LT recipients with excellent survival and low rejection rates and without increases in immunosuppression-related side effects. Liver Transpl, 2012. © 2012 AASLD.