bluuebunny/crossref_metadata_2025 huggingface dataset:
Protective Effects of Fermented Citrus Unshiu Peel Extract against Ultraviolet‐A‐induced Photoageing in Human Dermal Fibrobolasts
Authors: Bae Jun Tae , Ko Hyun Ju , Kim Gyoung Bum , Pyo Hyeong Bae , Lee Geun Soo
Published: March 2012

The aqueous extracts of Citrus unshiu peel containing flavonoid glycosides was used as co‐substrate with Schizophyllum commune mycelia producing β‐glucosidase and its biological activities were studied. β‐glucosidase‐produced S. commune mycelia converted the glycosides (narirutin and hesperidin) into aglycones (naringenin and hesperetin). The photoprotective potential of fermented C. unshiu peel extract with S. commune (S‐CPE) was tested in human dermal fibroblasts (HDFs) exposed to UVA. It was revealed that S‐CPE had an inhibitory effect on human interstitial collagenase (matrix metalloproteinase, MMP‐1) expression in UVA‐irradiated HDFs. The treatment of UVA‐irradiated HDFs with S‐CPE resulted in a dose‐dependent decrease in the expression level of MMP‐1 mRNA. The UVA irradiation raised the proportion of senescence‐associated β‐galactosidase (SA‐β‐gal) positive cells in comparison with the normal control group. The treatment of UVA‐irradiated HDFs with S‐CPE was shown to decrease the level of SA‐β‐gal (by approximately 45% at an S‐CPE concentration 0.1%, w/v) compared with the UVA‐irradiated HDFs. It was found that S‐CPE containing hesperetin has notable collagen biosynthetic activity for fibroblasts, indicating that S‐CPE can be promising cosmetic ingredients. Copyright © 2012 John Wiley & Sons, Ltd.
Feature Evaluation for Effective Bearing Prognostics
Authors: Camci F. , Medjaher K. , Zerhouni N. , Nectoux P.
Published: March 2012

Rolling element bearing failure is one of the foremost causes of breakdown in rotating machinery. It is not uncommon to replace a defected/used bearing with a new one that has shorter remaining useful life than the defected one. Thus, the prognostics of bearing plays critical role for increased availability and reduced cost. Effective prognostics highly depends on the quality of the extracted features. Diagnostics is basically a classification problem, whereas prognostics is the process of forecasting the future health states. The quality of the features for classification has been studied thoroughly. However, the evaluation of the quality of features for prognostics is a relatively new problem. This article presents an evaluation method for the goodness of the features for prognostics and presents results on bearings run until failure in a laboratory environment. Copyright © 2012 John Wiley & Sons, Ltd.
Reactivities of hydroxyl and perhydroxyl radicals toward cytosine and thymine: A comparative study
Authors: Yadav Amarjeet , Mishra P. C.
Published: March 2012

As the hydroxyl (OH) and perhydroxyl (OOH) radicals are known to play important roles in biological systems, their reactions with cytosine and thymine were studied. Addition reactions of these radicals at different sites of cytosine and thymine, and hydrogen abstraction reactions by each of the two radicals from the different sites of the two molecules were studied at the B3LYP/6‐31G(d,p), B3LYP/AUG‐cc‐pVDZ and BHandHLYP/AUG‐cc‐pVDZ levels of density functional theory. Effect of solvation in aqueous media on the reactions was studied at all these levels of theory using single point energy calculations using the polarizable continuum model. The present study shows that whereas the OH radical would abstract H atoms from the various sites of cytosine and thymine efficiently, the OOH radical would have poor reactivity in this regard. The OH radical is also predicted to be much more reactive than the OOH radical with regard to addition reactions at the C5 and C6 sites of both thymine and cytosine, though the OOH radical is also predicted to have significant reactivity in this respect. © 2012 Wiley Periodicals, Inc.
Probing the electronic structure, magnetotropicity, and absorption spectra of benzene trapped by lanthanide monoxides, C6H6···LnO, using DFT methods
Authors: Tsipis Athanassios , Gkarmpounis Dimitrios
Published: March 2012

The electronic properties and chemical bonding of the C6H6:LnO (Bz:LnO) adducts have been investigated by density functional theory (DFT) calculations. Two types (I and II) of Bz:LnO adducts are formed upon trapping LnO by the benzene molecule. In type I, the benzene molecule is coordinated to the Ln atom in a η6‐coordination mode with the LnO perpendicular to the ring center, while in type II the LnO is inclined with respect to the ring plane. In type II adducts, the benzene molecule undergoes significant structural distortions adopting a boat conformation facing the Ln atom of LnO. In the bending conformation of benzene, the bond length equalization is lifted up with the 1,2‐ and 4,5‐double bonds shortened by 0.01 Å with respect to the CC double bond in the “free” benzene molecule while the remaining bonds are lengthened by about 0.04 Å, thus coordinated benzene exhibits a 1,4‐diene type π‐localization within the ring. The effect of adduct formation on the structural, spectroscopic, and magnetotropic properties of the coordinated benzene have been explored using electronic structure computational techniques. The main features of the Time Dependent DFT (TD‐DFT) simulated absorption spectra of the LnOs and C6H6:LnO adducts are analyzed and assignments of the electronic transitions are given. © 2012 Wiley Periodicals, Inc.
Work Hardening Behavior of Ultrafine Grained Duplex Medium‐Mn Steels Processed by ART‐Annealing
Authors: Sun Rongmin , Xu Wenhuan , Wang Cunyu , Shi Jie , Dong Han , Cao Wenquan
Published: March 2012

The ultrafine grained duplex steels were fabricated by austenite reverted transformation annealing of the medium manganese steels after quenching or cold rolling. The microstructures were examined by scanning electron microscopy (SEM) and transmission electron microscopy (TEM) and X‐ray diffraction (XRD). The mechanical properties were determined by uniaxial tensile test. It was demonstrated that both the quenched and cold rolled structures were transformed into ultrafine grained duplex structures with large fractioned austenite by ART‐annealing. Long time annealing is essential to obtain the large fractioned austenite in quenched steel, but only short time annealing is needed to get large fractioned austenite in the cold rolled sheet. The mechanical examinations indicated that ART‐annealing results in the superhigh tensile elongation (>40%) and superhigh strength (1000 MPa) in quenched steels after long time annealing but in cold rolled steels after short time annealing. Based on the analysis on the work hardening behaviors of these ART‐annealed steels, the abnormal work hardening rate was presented and analyzed. The substantially enhanced ductility was attributed to the Lüders band propagation of the ferrite matrix and/or the TRIP effects of the large fractioned austenite. At last the dynamic phase natures of both fraction and stress was proposed to interpret the abnormal hardening behaviors and the “S” shaped stress–strain curves.
Starch properties of malted barley in relation to real degree of fermentation
Authors: Patindol James , Mendez‐Montealvo Guadalupe , Wang Ya‐Jane
Published: March 2012

Real degree of fermentation (RDF) is an important measure of brewhouse performance in the production of beer. In this work, the relationship of RDF with malted barley starch properties was investigated. Starches were isolated from 25 malted barley samples and analyzed for molecular size distribution (by HPSEC), AP structural features (by high‐performance size exclusion chromatography with multi‐angle laser light scattering and RI detectors), and thermal properties (by DSC). Cluster analysis, analysis of variance, principal component analysis, bivariate correlation, and multiple linear regression analysis were used in establishing correlations. RDF, AM, and AP content were 74.0–80.1%, 25.2–34.4%, and 65.6–74.9%, respectively. Starch gelatinization enthalpy was 6.4–8.1 J/g, and onset gelatinization temperature was 58.5–64.3°C. AP and AM content had a positive and negative impact on RDF, respectively. The effect of thermal properties (starch gelatinization and AM‐lipid complex melting) on RDF was not clear. Starch properties explained up to 86% of RDF variance to indicate that other malted barley constituents and/or properties also contribute to cultivar variations in RDF.
Exploring T and S parameters in Vector Meson Dominance models of strong electroweak symmetry breaking
Authors: Orgogozo Axel , Rychkov Slava
Published: March 2012

Abstract

We revisit the electroweak precision tests for Higgsless models of strong EWSB. We use the Vector Meson Dominance approach and express S and T via couplings characterizing vector and axial spin-1 resonances of the strong sector. These couplings are constrained by the elastic unitarity and by requiring a good UV behavior of various form- factors. We pay particular attention to the one-loop contribution of resonances to T (beyond the chiral log), and to how it can improve the fit. We also make contact with the recent studies of Conformal Technicolor. We explain why the second Weinberg sum rule never converges in these models, and formulate a condition necessary for preserving the custodial symmetry in the IR.
Human equilibrative nucleoside transporter 1 level does not predict prognosis in pancreatic cancer patients treated with neoadjuvant chemoradiation including gemcitabine
Authors: Kawada Natsuko , Uehara Hiroyuki , Katayama Kazuhiro , Nakamura Satoaki , Takahashi Hidenori , Ohigashi Hiroaki , Ishikawa Osamu , Nagata Shigenori , Tomita Yasuhiko
Published: March 2012

Background

Gemcitabine is a key drug for the treatment of pancreatic cancer. Human equilibrative nucleoside transporter 1 (hENT1) is a major transporter responsible for gemcitabine uptake into cells. This study was conducted to elucidate the association between expression level of hENT1 and outcome for pancreatic cancer patients treated with neoadjuvant therapy including gemcitabine.

Methods

Sixty‐three patients who underwent neoadjuvant chemoradiation followed by curative surgery for pancreatic ductal adenocarcinomas were included. Immunohistochemistry was performed using resected specimens and the staining intensity of hENT1 was scored as having no staining, low staining, or high staining; the former two were defined as negative expression of hENT1. The association between expression level of hENT1 and overall survival was evaluated by Cox proportional regression model.

Results

Expression level of hENT1 was evaluated as positive in 22 (35%) patients, and as negative in 41 (65%) patients. Univariate analysis showed that regional lymph node metastasis, vascular permeation, and perineural invasion are prognostic factors; however, expression level of hENT1 did not reach statistical significance. Multivariate analysis showed only vascular permeation as a prognostic factor.

Conclusions

Expression level of hENT1 was not associated with prognosis for pancreatic cancer patients who were treated with neoadjuvant chemoradiation including gemcitabine.
The conundrum of iron in multiple sclerosis – time for an individualised approach
Authors: van Rensburg Susan J. , Kotze Maritha J. , van Toorn Ronald
Published: March 2012

Although the involvement of immune mechanisms in multiple sclerosis (MS) is undisputed, some argue that there is insufficient evidence to support the hypothesis that MS is an autoimmune disease, and that the difference between immune- and autoimmune disease mechanisms has yet to be clearly delineated. Uncertainties surrounding MS disease pathogenesis and the modest efficacy of currently used disease modifying treatments (DMTs) in the prevention of disability, warrant the need to explore other possibilities. It is evident from the literature that people diagnosed with MS differ widely in symptoms and clinical outcome - some patients have a benign disease course over many years without requiring any DMTs. Attempting to include all patients into a single entity is an oversimplification and may obscure important observations with therapeutic consequences. In this review we advocate an individualised approach named Pathology Supported Genetic Testing (PSGT), in which genetic tests are combined with biochemical measurements in order to identify subgroups of patients requiring different treatments. Iron dysregulation in MS is used as an example of how this approach may benefit patients. The theory that iron deposition in the brain contributes to MS pathogenesis has caused uncertainty among patients as to whether they should avoid iron. However, the fact that a subgroup of people diagnosed with MS show clinical improvement when they are on iron supplementation emphasises the importance of individualised therapy, based on genetic and biochemical determinations.
Small bowel MR enterography: problem solving in Crohn’s disease
Authors: Griffin Nyree , Grant Lee Alexander , Anderson Simon , Irving Peter , Sanderson Jeremy
Published: March 2012

Magnetic resonance enterography (MRE) is fast becoming the first-line radiological investigation to evaluate the small bowel in patients with Crohn’s disease. It can demonstrate both mural and extramural complications. The lack of ionizing radiation, together with high-contrast resolution, multiplanar capability and cine-imaging make it an attractive imaging modality in such patients who need prolonged follow-up. A key question in the management of such patients is the assessment of disease activity. Clinical indices, endoscopic and histological findings have traditionally been used as surrogate markers but all have limitations. MRE can help address this question. The purpose of this pictorial review is to (1) detail the MRE protocol used at our institution; (2) describe the rationale for the MR sequences used and their limitations; (3) compare MRE with other small bowel imaging techniques; (4) discuss how MRE can help distinguish between inflammatory, stricturing and penetrating disease, and thus facilitate management of this difficult condition.

Main Messages

• MR enterography (MRE) is the preferred imaging investigation to assess Crohn’s disease. T2-weighted, post-contrast and diffusion-weighted imaging (DWI) can be used.

• MRE offers no radiation exposure, high-contrast resolution, multiplanar ability and cine imaging.

• MRE can help define disease activity, a key question in the management of Crohn’s disease.

• MRE can help distinguish between inflammatory, stricturing and penetrating disease.

• MRE can demonstrate both mural and extramural complications.
Widowhood and Mortality: A Meta-Analysis and Meta-Regression
Authors: Shor Eran , Roelfs David J. , Curreli Misty , Clemow Lynn , Burg Matthew M. , Schwartz Joseph E.
Published: March 2012

The study of spousal bereavement and mortality has long been a major topic of interest for social scientists, but much remains unknown with respect to important moderating factors, such as age, follow-up duration, and geographic region. The present study examines these factors using meta-analysis. Keyword searches were conducted in multiple electronic databases, supplemented by extensive iterative hand searches. We extracted 1,377 mortality risk estimates from 123 publications, providing data on more than 500 million persons. Compared with married people, widowers had a mean hazard ratio (HR) of 1.23 (95% confidence interval (CI), 1.19–1.28) among HRs adjusted for age and additional covariates and a high subjective quality score. The mean HR was higher for men (HR, 1.27; 95% CI, 1.19–1.35) than for women (HR, 1.15; 95% CI, 1.08–1.22). A significant interaction effect was found between gender and mean age, with HRs decreasing more rapidly for men than for women as age increased. Other significant predictors of HR magnitude included sample size, geographic region, level of statistical adjustment, and study quality.
Estimating Mortality Differences in Developed Countries From Survey Information on Maternal and Paternal Orphanhood
Authors: Luy Marc
Published: March 2012

In general, the use of indirect methods is limited to developing countries. Developed countries are usually assumed to have no need to apply such methods because detailed demographic data exist. However, the potentialities of demographic analysis with direct methods are limited to the characteristics of available macro data on births, deaths, and migration. For instance, in many Western countries, official population statistics do not permit the estimation of mortality by socioeconomic status (SES) or migration background, or for estimating the relationship between parity and mortality. In order to overcome these shortcomings, I modify and extend the so-called orphanhood method for indirect estimation of adult mortality from survey information on maternal and paternal survival to allow its application to populations of developed countries. The method is demonstrated and tested with data from two independent Italian cross-sectional surveys by estimating overall and SES-specific life expectancy. The empirical applications reveal that the proposed method can be used successfully for estimating levels and trends of mortality differences in developed countries and thus offers new prospects for the analysis of mortality.
Selection of Symptomatic Patients with Crohn's Disease for Abdominopelvic Computed Tomography: Role of Serum C-Reactive Protein
Authors: Desmond Alan N. , O'Regan Kevin , Malik Neera , McWilliams Sebastian , O'Neill Siobhan , Quigley Eamonn M. , Shanahan Fergus , Maher Michael M.
Published: March 2012

Background

Results of previous studies have shown that repeated abdominopelvic computed tomography (CT) examinations can lead to substantial cumulative diagnostic radiation exposure in patients with Crohn's disease (CD). Improved selection of patients referred for CT will reduce unnecessary radiation exposure. This study examines if serum C-reactive protein (CRP) concentration predicts which symptomatic patients with CD are likely to have significant disease activity or disease complications (such as abscess) detected on abdominopelvic CT.

Methods

All abdominopelvic CTs performed on patients with CD at a tertiary referral centre during the period June 2003 to June 2008 were identified. CT findings were coded by a pair of independent blinded senior radiologists for (i) small bowel luminal disease, (ii) large bowel luminal disease, (iii) mesenteric inflammatory changes, (iv) penetrating disease (fistulas, abscess, or phlegmon), (v) acute disease complications (obstruction or perforation), and (vi) acute non-CD findings. Imaging findings were correlated with serum CRP checked within 14 days before imaging. The reference range for CRP was defined as 0–5 mg/L.

Results

A total of 147 patients with symptomatic CD had a CRP assay performed within 14 days before undergoing abdominopelvic CT. The median time from CRP assay to imaging was 2 days (interquartile range, 0-6 days). Median CRP before imaging was 24 mg/L (interquartile range, 6-88 mg/L). CT was normal in 34 of 147 case (23.1%). Patients with normal CRP (n = 36) were significantly less likely to have penetrating disease (odds ratio [OR], 0.04 [95% confidence interval {CI}, 0.01-0.7]; P < .001) or large bowel luminal disease (OR, 0.3 [95% CI, 0.1-0.8]; P < .05). Normal CRP excluded penetrating disease with a sensitivity of 1.0 (95% CI, 0.87-1.0). CRP levels did not correlate with the presence of small bowel luminal disease (n = 82), mesenteric inflammatory changes (n = 68), or acute disease complications (n = 10).

Conclusion

Symptomatic patients with CD and normal serum CRP are unlikely to have evidence of abscess, fistulating disease, or large bowel luminal disease detected on abdominopelvic CT. However, abdominopelvic CT may demonstrate evidence of clinically significant non-penetrating CD or complications, including perforation and acute obstruction, regardless of serum CRP concentration.
Low‐resolution structure of Drosophila translin
Authors: Kumar Vinay , Gupta Gagan D.
Published: March 2012

Crystals of native Drosophila melanogaster translin diffracted to 7 Å resolution. Reductive methylation of the protein improved crystal quality. The native and methylated proteins showed similar profiles in size‐exclusion chromatography analyses but the methylated protein displayed reduced DNA‐binding activity. Crystals of the methylated protein diffracted to 4.2 Å resolution at BM14 of the ESRF synchrotron. Crystals with 49% solvent content belonged to monoclinic space group P21 with eight protomers in the asymmetric unit. Only 2% of low‐resolution structures with similar low percentage solvent content were found in the PDB. The crystal structure, solved by molecular replacement method, refined to Rwork (Rfree) of 0.24 (0.29) with excellent stereochemistry. The crystal structure clearly shows that drosophila protein exists as an octamer, and not as a decamer as expected from gel‐filtration elution profiles. The similar octameric quaternary fold in translin orthologs and in translin–TRAX complexes suggests an up‐down dimer as the basic structural subunit of translin‐like proteins. The drosophila oligomer displays asymmetric assembly and increased radius of gyration that accounts for the observed differences between the elution profiles of human and drosophila proteins on gel‐filtration columns. This study demonstrates clearly that low‐resolution X‐ray structure can be useful in understanding complex biological oligomers.
Reconstructing schemes from the derived category
Authors: de Salas Carlos Sancho , de Salas Fernando Sancho
Published: March 2012

We generalize Bondal and Orlov's Reconstruction Theorem for a Gorenstein schemeXand a projective morphismX→Twhose (relative) dualizing sheaf is eitherT-ample orT-antiample.
Muslim Reformists, Female Citizenship, and the Public Accommodation of Islam in Liberal Democracy
Authors: Fadel Mohammad
Published: March 2012

The European Court of Human Rights (ECHR), in a trilogy of cases involving Muslim claimants, has granted state parties to the European Convention on Human Rights a wide margin of appreciation with respect to the regulation of public manifestations of Islam. The ECHR has justified its decisions in these cases on the grounds that Islamic symbols, such as the ḥijāb, or Muslim commitments to the shari‘a — Islamic law — are inconsistent with the democratic order of Europe. This article raises the question of what kinds of commitments to gender equality and democratic decision-making are sufficient for a democratic order, and whether modernist Islamic teachings manifest a satisfactory normative commitment in this regard. It uses the arguments of two modern Muslim reformist scholars — Yūsuf al-Qaraḍāwī and ‘Abd al-Ḥalīm Abū Shuqqa — as evidence to argue that if the relevant degree of commitment to gender equality is understood from the perspective of political rather than comprehensive liberalism, doctrines such as those elaborated by these two religious scholars evidence sufficient commitment to the value of political equality between men and women. This makes less plausible the ECHR's arguments justifying a different treatment of Muslims on account of alleged Islamic commitments to gender hierarchy. It also argues that in light of Muslim modernist conceptions of the shari‘a, there is no normative justification to conclude that faithfulness to the shari‘a entails a categorical rejection of democracy as the ECHR suggested.
Excitation mechanisms and spectral properties of the ion‐cyclotron parallel‐velocity shear driven instability
Authors: Mikhailenko V. S. , Chibisov D. V. , Koepke M. E.
Published: March 2012

The electrostatic ion cyclotron parallel‐velocity shear driven instability, and its associated oscillatory mode, is investigated analytically. It is shown that three distinct mechanisms are responsible for this instability, specifically, the ion‐kinetic, ion‐hydrodynamic and electron‐kinetic mechanisms. In separate magnitude ranges of the normalized parallel‐wavelength component, a different mechanism dominates, with a transition in each overlapping region. The linearized dispersion equation is solved within these ranges where the effects of inverse ion cyclotron damping, ion hydrodynamic, and inverse electron Landau damping alternately dominate, respectively, in the development of ion cyclotron oscillations. A general criterion of instability is determined by expressing the destabilizing effect of the velocity shear in terms of the perpendicular(magnetic field‐normal) component of the wave vector.
Modeling and analyzing observed transverse sand bars in the surf zone
Authors: Ribas F. , de Swart H. E. , Calvete D. , Falqués A.
Published: March 2012

A morphodynamic model has been applied to explain the characteristics of transverse sandbars observed in the inner surf zone of open beaches. The model describes the feedback between waves, rollers, depth‐averaged currents and bed evolution, so that self‐organized processes can develop. The modeled bar characteristics, i.e. wavelength (30–70 m), crest orientation (up‐current) and the e‐folding growth time (about 12 hr) are in good agreement with those of observed transverse bars at Noordwijk beach, the Netherlands, but modeled migration speeds (tens of meters per day), turn out to be a factor 2 larger than those observed. The wavelength increases with the distance between the shoreline and the peak of the longshore current and the migration speed is correlated with the maximum longshore current. The model also explains why transverse bar formation at Noordwijk occurs for obliquely incident waves of intermediate heights. Realistic positive feedback leading to formation of up‐current oriented bars like those observed is only obtained if a term related to the turbulence sediment resuspension created by the rollers is included in the transport formula. In that case, the depth‐averaged sediment concentration decreases seaward across the inner surf zone, enhancing the convergence of sediment transport in the offshore directed flow perturbations that occur over the up‐current bars. This offshore current deflection is mainly caused by frictional torques, but the roller radiation stresses also play an important role.
MST radar observations of short‐period gravity wave during overhead tropical cyclone
Authors: Das Siddarth Shankar , Uma K. N. , Das Subrata Kumar
Published: March 2012

Short‐period gravity waves associated with the passage of tropical cyclone using mesosphere‐stratosphere‐troposphere (MST) radar located at Gadanki (13.5°N, 79.2°E) has been discussed. The observed stratospheric gravity wave is found to have a periodicity of ∼42 min, vertical and horizontal wavelength of ∼3.5 km and 14 km, respectively. Maximum amplitude of gravity wave is observed in the upper troposphere and lower stratosphere (UTLS) region due to which periodic updrafts and downdrafts are observed. This weakens the stability of tropopause, which is observed in radar signal‐to‐noise ratio (SNR). The enhancement of vertical momentum flux of order ∼−0.6 m2/s2 observed in the lower stratosphere is attributed to the cyclone generated gravity waves. The obstacle effect is found to be the generative mechanism for the observed gravity waves associated with the tropical cyclone.
Modeling Arecibo conjugate heating effects with SAMI2
Authors: Wu T.‐W. , Huba J. D. , Joyce G. , Bernhardt P. A.
Published: March 2012

Conjugate heating effects associated with the upcoming Arecibo heater facility are studied using the NRL ionosphere model SAMI2. A density‐dependent, localized heating source is included in the electron temperature equation to model ionospheric radiowave heating. Heating effects are examined as a function of the heating timing and the peak density of the unmodified ionosphere (through the F10.7 index). The simulation results suggest that field‐aligned duct formation occur during periods of relatively low electron densities (e.g., during the night). The enhancement of the electron temperature and electron density in the conjugate topside ionosphere (∼500 km) could reach respective values of ∼5% and 25%. Heating losses associated with inelastic electron‐neutral (N2) collisions primarily inhibit conjugate effects.
Early life antibiotic‐driven changes in microbiota enhance susceptibility to allergic asthma
Authors: Russell Shannon L , Gold Matthew J , Hartmann Martin , Willing Benjamin P , Thorson Lisa , Wlodarska Marta , Gill Navkiran , Blanchet Marie‐Renée , Mohn William W , McNagny Kelly M , Finlay Brett B
Published: March 2012

Allergic asthma rates have increased steadily in developed countries, arguing for an environmental aetiology. To assess the influence of gut microbiota on experimental murine allergic asthma, we treated neonatal mice with clinical doses of two widely used antibiotics—streptomycin and vancomycin—and evaluated resulting shifts in resident flora and subsequent susceptibility to allergic asthma. Streptomycin treatment had little effect on the microbiota and on disease, whereas vancomycin reduced microbial diversity, shifted the composition of the bacterial population and enhanced disease severity. Neither antibiotic had a significant effect when administered to adult mice. Consistent with the ‘hygiene hypothesis’, our data support a neonatal, microbiota‐driven, specific increase in susceptibility to experimental murine allergic asthma.
Get your fingers out of p53's way!
Authors: Bublik Débora Rosa , Oren Moshe
Published: March 2012

Premature triggering of cell death by p53 has to be avoided. A recent study in EMBO reports demonstrates how the anti‐apoptotic protein Apak represses the expression of the pro‐apoptotic p53 target gene p53AIP1 in non‐stressed cells.
Replicates and repeats—what is the difference and is it significant?
Authors: Vaux David L , Fidler Fiona , Cumming Geoff
Published: March 2012

Replicate samples are important, but they cannot be used to properly test the validity of a scientific hypothesis.
Associations of Variants in FTO and Near MC4R With Obesity Traits in South Asian Indians
Authors: Vasan Senthil K. , Fall Tove , Neville Matthew J. , Antonisamy Belavendra , Fall Caroline H. , Geethanjali Finney S. , Gu Harvest F. , Raghupathy Palany , Samuel Prasanna , Thomas Nihal , Brismar Kerstin , Ingelsson Erik , Karpe Fredrik
Published: March 2012

Recent genome‐wide association studies show that loci in FTO and melanocortin 4 receptor (MC4R) associate with obesity‐related traits. Outside Western populations the associations between these variants have not always been consistent and in Indians it has been suggested that FTO relates to diabetes without an obvious intermediary obesity phenotype. We investigated the association between genetic variants in FTO (rs9939609) and near MC4R (rs17782313) with obesity‐ and type 2 diabetes (T2DM)‐related traits in a longitudinal birth cohort of 2,151 healthy individuals from the Vellore birth cohort in South India. The FTO locus displayed significant associations with several conventional obesity‐related anthropometric traits. The per allele increase is about 1% for BMI, waist circumference (WC), hip circumference (HC), and waist—hip ratio. Consistent associations were observed for adipose tissue‐specific measurements such as skinfold thickness reinforcing the association with obesity‐related traits. Obesity associations for the MC4R locus were weak or nonsignificant but a signal for height (P < 0.001) was observed. The effect on obesity‐related traits for FTO was seen in adulthood, but not at younger ages. The loci also showed nominal associations with increased blood glucose but these associations were lost on BMI adjustment. The effect of FTO on obesity‐related traits was driven by an urban environmental influence. We conclude that rs9939609 variant in the FTO locus is associated with measures of adiposity and metabolic consequences in South Indians with an enhanced effect associated with urban living. The detection of these associations in Indians is challenging because conventional anthropometric obesity measures work poorly in the Indian “thin‐fat” phenotype.
Acute Exercise and Training Alter Blood Lipid and Lipoprotein Profiles Differently in Overweight and Obese Men and Women
Authors: Greene Nicholas P. , Martin Steven E. , Crouse Stephen F.
Published: March 2012

Our purpose was to elucidate effects of acute exercise and training on blood lipids‐lipoproteins, and high‐sensitivity C‐reactive protein (hsCRP) in overweight/obese men (n = 10) and women (n = 8); age, BMI, body fat percentage, and VO2max were (mean ± SEM): 45 ± 2.5 years, 31.9 ± 1.4 kg·m−2, 41.1 ± 1.5%, and 25.2 ± 1.3 mlO2·kg−1·min−1. Before exercise training subjects performed an acute exercise session on a treadmill (70% VO2max, 400 kcal energy expenditure), followed by 12 weeks of endurance exercise training (land‐based or aquatic‐based treadmill): 3 sessions·week−1, progressing to 500 kcal·session−1 during which subjects maintained accustomed dietary habits. After training, the acute exercise session was repeated. Blood samples, obtained immediately before and 24 h after acute exercise sessions, were analyzed for serum lipids, lipoproteins, and hsCRP adjusted for plasma volume shifts. Exercise training increased VO2max (+3.67 mlO2·kg−1·min−1, P < 0.001) and reduced body weight (−2.7 kg, P < 0.01). Training increased high‐density lipoprotein (HDL) and HDL2b‐cholesterol (HDL‐C) concentrations (+3.7 and +2.4 mg·dl−1, P < 0.05) and particle numbers (+588 and +206 nmol·l−1, P < 0.05) in men. In women despite no change in total HDL‐C, subfractions shifted from HDL3‐C (−3.2, P < 0.01) to HDL2b‐C (+3.5, P < 0.05) and HDL2a‐C (+2.2 mg·dl−1, P < 0.05), with increased HDL2b particle number (+313 nmol·l−1, P < 0.05). Training reduced LDL3 concentration and particle number in women (−1.6 mg·dl−1 and −16 nmol·l−1, P < 0.05). Acute exercise reduced the total cholesterol (TC): HDL‐C ratio in men (−0.16, P < 0.01) and increased hsCRP in all subjects (+0.05 mg·dl−1, P < 0.05), regardless of training. Training did not affect acute exercise responses. Our data support the efficacy of endurance training, without dietary intervention, to elicit beneficial changes in blood lipids‐lipoproteins in obese men and women.
Differential Diagnosis of Hyperandrogenism in Women with Polycystic Ovary Syndrome
Authors: Rachoń D.
Published: March 2012

According to the Androgen Excess and Polycystic Ovary Syndrome Society (AE&PCOS), the main feature of PCOS is clinical hyperandrogenism or laboratory hyperandrogenaemia. Therefore, in diagnosing PCOS one must always exclude other causes of androgen excess. In a woman with hyperandrogenism, the diagnosis of PCOS can usually be made according to the patient’s history and careful clinical examination. Signs of mild hyperandrogenaemia usually start after the menarche and cycles continue to be anovulatory in adult life. Non-classical congenital adrenal hyperplasia (NCCAH) can be another cause of hyperandrogenism with oligomenorrhea. This can be diagnosed in a patient with elevated basal or ACTH stimulated serum 17OH-progesterone (17-OHP) levels or in a case of a significant decrease in serum testosterone (TST) and dehydroepiandrosterone sulphate (DHEA-S) in a two day dexamethasone suppression test. Cushing’s disease (ACTH producing pituitary adenoma) is a rare cause of hyperandrogenaemia in women with recent onset of hyperandrogenism. However, it must always be taken into the consideration in a patient with accompanying signs of hypercortisolism. It can usually be excluded by performing an overnight dexamethasone suppression test or the measurement of 24 h urinary free cortisol levels. Severe signs of hyperandrogenism which lead to virilization should always lead to the exclusion of androgen secreting tumors of ovarian or adrenal origin. These are very rare but should be always taken into the account in a patient with recent onset of severe signs of androgen excess and very high serum androgen levels. Mild signs of hyperandrogenaemia in a woman with recent oligomenorrhea should always lead to the exclusion of hyperprolactinaemia.
Shaggy/glycogen synthase kinase 3β and phosphorylation of Sarah/regulator of calcineurin are essential for completion of
Drosophila
female meiosis
Authors: Takeo Satomi , Swanson Selene K. , Nandanan Kavyasree , Nakai Yasuhiro , Aigaki Toshiro , Washburn Michael P. , Florens Laurence , Hawley R. Scott
Published: March 2012

The Ca
2+
/Calmodulin-dependent phosphatase calcineurin is essential for exit from meiotic arrest at metaphases I and II in
Drosophila
and
Xenopus
oocytes. We previously found that Sarah, the
Drosophila
homolog of regulator of calcineurin, acts as a positive regulator of calcineurin and is required to complete anaphase I of female meiosis. Here, we undertook biochemical approaches, including MS and posttranslational modification analyses, to better understand the mechanism by which Sarah regulates calcineurin. A search for phosphorylated residues revealed that Sarah is highly phosphorylated at Ser100, Thr102, and Ser219 in both ovaries and activated eggs and that Ser215 is phosphorylated only in activated eggs. Functional analyses using mutant forms of Sarah showed that phosphorylation at Ser215, a consensus phosphorylation site for glycogen synthase kinase 3β (GSK-3β) and its priming kinase site Ser219, are essential for Sarah function. Furthermore, germ-line clones homozygous for a null allele of
shaggy
(
Drosophila
GSK-3β) both fail to complete meiosis and lack phosphorylation of Sarah at Ser215, suggesting that the phosphorylation of Sarah by Shaggy/GSK-3β is required to complete meiosis. Our findings suggest a mechanism in which Shaggy/GSK-3β activates calcineurin through Sarah phosphorylation on egg activation in
Drosophila
.
Lipid-derived nanoparticles for immunostimulatory RNA adjuvant delivery
Authors: Nguyen David N. , Mahon Kerry P. , Chikh Ghania , Kim Phillip , Chung Hattie , Vicari Alain P. , Love Kevin T. , Goldberg Michael , Chen Steve , Krieg Arthur M. , Chen Jianzhu , Langer Robert , Anderson Daniel G.
Published: March 2012

The specific activation of Toll-like receptors (TLRs) has potential utility for a variety of therapeutic indications including antiviral immunotherapy and as vaccine adjuvants. TLR7 and TLR 8 may be activated by their native ligands, single-stranded RNA, or by small molecules of the imidazoquinoline family. However the use of TLR7/8 agonists for in vivo therapy is limited by instability, in the case of RNA, or systemic biodistribution and toxicity in the case of small molecule agonists. We hypothesized that unique lipid-like materials, termed “lipidoids,” could be designed to efficiently deliver immunostimulatory RNA (isRNA) to TLR-expressing cells to drive innate and adaptive immune responses. A library of lipidoids was synthesized and screened for the ability to induce type I IFN activation in human peripheral blood mononuclear cells when combined with isRNA oligonucleotides. Effective lipidoid-isRNA nanoparticles, when tested in mice, stimulated strong IFN-α responses following subcutaneous injection, had robust antiviral activity that suppressed influenza virus replication, and enhanced antiovalbumin humoral and cell-mediated responses when used as a vaccine adjuvant. Further, we demonstrate that whereas all immunological activity was MyD88-dependent, certain materials were found to engage both TLR7-dependent and TLR7-independent activity in the mouse suggestive of cell-specific delivery. These lipidoid formulations, which are materials designed specifically for delivery of isRNA to Toll-like receptors, were superior to the commonly used
N
-[1-(2,3-dioleoyloxy)propyl]-
N,N,N
-trimethylammonium methylsulfate–RNA delivery system and may provide new tools for the manipulation of TLR responses in vitro and in vivo.
Innovation with ‘Chinese’ characteristics? Reflecting on the implications of an ethnic-based paradigm of management and innovation
Authors: Goxe François
Published: March 2012

Cultural studies seem to dominate the field of management and innovation in China. Researchers have defined and considered Confucianism and a number of common, transnational Asian/Chinese values and practices allegedly unifying China and parts of East Asia. These values and practices have been erected as the cultural pillars of ‘Chinese management’, ‘Chinese entrepreneurship’ and, more recently, ‘indigenous innovation’ in the ethnic Chinese world and now mainland China. We believe these values and practices, frequently claimed as unique and fueling innovation in Chinese firms, to be potentially manipulated for strategic purposes, by political authorities as well as business organizations. This paper examines the aforementioned premises and questions the notions of Chinese ethnicity, values, management and innovation from political and strategic perspectives. We first present the emergence of Chinese values and Chinese management. We then consider this emergence in relation to political agendas and the renewal of Asianism or New Confucianism. The second part of the paper analyzes how such values and ethnicity can be utilized by entrepreneurs for both defensive and offensive business purposes. We then illustrate our debate with some reflections on the Shanzhai form of indigenous innovation before concluding with implications for researchers, managers and entrepreneurs and discussing the dangers of exoticism and avenues for future empirical research.
The determinants of and barriers to critical consumption: a study of Addiopizzo
Authors: Partridge Henry
Published: March 2012

‘Addiopizzo’ (Goodbye protection money) is a grassroots anti-mafia movement based in Palermo that stresses the individual consumer's responsibility for maintaining the Sicilian mafia's pizzo system. If you purchase products from a business that pays the pizzo you are indirectly supporting the mafia. By encouraging Palermitans to buy from ‘pizzo-free’ businesses, Addiopizzo uses the purchasing power of the consumer to fight organised crime. The community of ‘pizzo-free’ businesses is small but steadily growing whilst the number of critical consumers pledging to buy their products appears to have peaked. This article aims to investigate the reasons why consumers may be reluctant to support ‘pizzo-free’ businesses by asking those who have already made public their decision to do so. Whilst critical consumers cannot fully explain why the majority of Palermo's citizens continue to tolerate the pizzo system their attitudes towards them do highlight differences that may help to account for wider non-participation in Addiopizzo's campaign.
Pancreatic Cancer
Authors: Sood Ruchit , Neoh Karen , Bakashi Ranjeeta , Argyle Katherine , Toner Rodger
Published: March 2012

Pancreatic cancer is the tenth most common cancer in the UK and the fifth leading cause of cancer death (UK). According to the Office for National Statistics, there were 8085 new cases and 7781 deaths in 2008, highlighting its extremely poor prognosis. The average-size GP practice is likely to see at least one case of pancreatic cancer per year. Currently, only 13% of cases are diagnosed through the 2 week wait referral pathway, with 47% presenting as hospital emergencies. Delay in diagnosis can be multifactorial. Early symptoms tend to be non-specific and signs and symptoms such as painless jaundice and weight loss do not present until late stages. Early recognition by the GP is crucial as surgical resection offers the best chance of survival. GPs also play a crucial role in providing palliative care in patients who have unresectable disease.
A Bayesian Poisson Vector Autoregression Model
Authors: Brandt Patrick T. , Sandler Todd
Published: March 2012

Multivariate count models are rare in political science despite the presence of many count time series. This article develops a new Bayesian Poisson vector autoregression model that can characterize endogenous dynamic counts with no restrictions on the contemporaneous correlations. Impulse responses, decomposition of the forecast errors, and dynamic multiplier methods for the effects of exogenous covariate shocks are illustrated for the model. Two full illustrations of the model, its interpretations, and results are presented. The first example is a dynamic model that reanalyzes the patterns and predictors of superpower rivalry events. The second example applies the model to analyze the dynamics of transnational terrorist targeting decisions between 1968 and 2008. The latter example's results have direct implications for contemporary policy about terrorists' targeting that are both novel and innovative in the study of terrorism.
Identification and characterization of ToRC, a novel ISWI-containing ATP-dependent chromatin assembly complex
Authors: Emelyanov Alexander V. , Vershilova Elena , Ignatyeva Maria A. , Pokrovsky Daniil K. , Lu Xingwu , Konev Alexander Y. , Fyodorov Dmitry V.
Published: March 2012

SNF2-like motor proteins, such as ISWI, cooperate with histone chaperones in the assembly and remodeling of chromatin. Here we describe a novel, evolutionarily conserved, ISWI-containing complex termed ToRC (Toutatis-containing chromatin remodeling complex). ToRC comprises ISWI, Toutatis/TIP5 (TTF-I-interacting protein 5), and the transcriptional corepressor CtBP (C-terminal-binding protein). ToRC facilitates ATP-dependent nucleosome assembly in vitro. All three subunits are required for its maximal biochemical activity. The toutatis gene exhibits strong synthetic lethal interactions with CtBP. Thus, ToRC mediates, at least in part, biological activities of CtBP and Toutatis. ToRC subunits colocalize in euchromatic arms of polytene chromosomes. Furthermore, nuclear localization and precise distribution of ToRC in chromosomes are dependent on CtBP. ToRC is involved in CtBP-mediated regulation of transcription by RNA polymerase II in vivo. For instance, both Toutatis and CtBP are required for repression of genes of a proneural gene cluster, achaete–scute complex (AS-C), in Drosophila larvae. Intriguingly, native C-terminally truncated Toutatis isoforms do not associate with CtBP and localize predominantly to the nucleolus. Thus, Toutatis forms two alternative complexes that have differential distribution and can participate in distinct aspects of nuclear DNA metabolism.
Dynamic Nucleotide-Binding Site and Leucine-Rich Repeat-Encoding Genes in the Grass Family
Authors: Luo Sha , Zhang Yu , Hu Qun , Chen Jiongjiong , Li Kunpeng , Lu Chen , Liu Hui , Wang Wen , Kuang Hanhui
Published: March 2012

The proper use of resistance genes (R genes) requires a comprehensive understanding of their genomics and evolution. We analyzed genes encoding nucleotide-binding sites and leucine-rich repeats in the genomes of rice (Oryza sativa), maize (Zea mays), sorghum (Sorghum bicolor), and Brachypodium distachyon. Frequent deletions and translocations of R genes generated prevalent presence/absence polymorphism between different accessions/species. The deletions were caused by unequal crossover, homologous repair, nonhomologous repair, or other unknown mechanisms. R gene loci identified from different genomes were mapped onto the chromosomes of rice cv Nipponbare using comparative genomics, resulting in an integrated map of 495 R loci. Sequence analysis of R genes from the partially sequenced genomes of an African rice cultivar and 10 wild accessions suggested that there are many additional R gene lineages in the AA genome of Oryza. The R genes with chimeric structures (termed type I R genes) are diverse in different rice accessions but only account for 5.8% of all R genes in the Nipponbare genome. In contrast, the vast majority of R genes in the rice genome are type II R genes, which are highly conserved in different accessions. Surprisingly, pseudogene-causing mutations in some type II lineages are often conserved, indicating that their conservations were not due to their functions. Functional R genes cloned from rice so far have more type II R genes than type I R genes, but type I R genes are predicted to contribute considerable diversity in wild species. Type I R genes tend to reduce the microsynteny of their flanking regions significantly more than type II R genes, and their flanking regions have slightly but significantly lower G/C content than those of type II R genes.