bluuebunny/crossref_metadata_2025 huggingface dataset:
Recent increase in high tropical cyclone heat potential area in the Western North Pacific Ocean
Authors: Pun Iam‐Fei , Lin I.‐I. , Lo Min‐Hui
Published: May 2013

The Main Development Region (MDR) for tropical cyclones (TCs) in the western North Pacific Ocean is the most active TC region in the world. Based on synergetic analyses of satellite altimetry and gravity observations, we found that the subsurface ocean conditions in the western North Pacific MDR has become even more favorable for the intensification of typhoons and supertyphoons. Compared to the early 1990s, a 10% increase in both the depth of the 26°C isotherm (D26) and Tropical Cyclone Heat Potential (TCHP) has occurred in the MDR. In addition, the areas of high TCHP (≥ 110 kJ cm−2) and large D26 (≥ 110 m) have 13% and 17% increases, respectively. Because these high TCHP and large D26 regions are often associated with intensification of the most intense TCs (i.e. supertyphoons), this recent warming requires close attention and monitoring.
DO THEY KNOW WHAT IS AT RISK? HEALTH RISK PERCEPTION AMONG THE OBESE
Authors: Winter Joachim , Wuppermann Amelie
Published: May 2013

The perception of health risks and risky health behaviors are closely associated. In this paper, we investigate the accuracy of health risk perceptions among obese individuals, aged 50–62 years. We compare subjective risk perceptions for various diseases elicited in the American Life Panel to individual's objective risks of the same diseases. We find that obese individuals significantly underestimate their 5‐year risks of arthritis or rheumatism and hypertension, whereas they systematically overestimate their 5‐year risks of a heart attack and a stroke. Obese individuals are thus aware of some but not all obesity‐related health risks. For given diseases, we document substantial heterogeneities in the accuracy of expectations across individuals. Copyright © 2013 John Wiley & Sons, Ltd.
Inhibition of Hepatitis B Virus–Associated Liver Cancer by Antiplatelet Therapy: A Revolution in Hepatocellular Carcinoma Prevention?
Authors: Calvisi Diego F.
Published: May 2013

Abstract

Chronic infection with hepatitis B virus (HBV) is a major risk factor for the development of hepatocellular carcinoma (HCC). The pathogenesis of HBV-associated HCC involves both viral and host factors. The latter include a functionally inefficient CD8+ T-cell response that fails to clear the infection from the liver but sustains a chronic necroinflammatory process that contributes to the development of HCC. According to this scenario, amelioration of immune-mediated chronic liver injury may prevent HCC. Because platelets facilitate immune-mediated liver injury by promoting the hepatic accumulation of virus-specific CD8+ T cells, we evaluated the long-term consequences of antiplatelet therapy in an HBV transgenic mouse model of chronic immune-mediated necroinflammatory liver disease that progresses to HCC. Treatment with aspirin and clopidogrel during the chronic phase of the disease diminished the number of intrahepatic HBV-specific CD8+ T cells and HBV-nonspecific inflammatory cells, the severity of liver fibrosis, and the development of HCC. Antiplatelet therapy improved overall survival without causing significant side effects. In contrast, the same antiplatelet regimen had no antitumor effect when HCC was induced nonimmunologically by chronic exposure to a hepatotoxic chemical. The unprecedented observation that antiplatelet therapy inhibits or delays immune-mediated hepatocarcinogenesis suggests that platelets may be key players in the pathogenesis of HBV-associated liver cancer and supports the notion that immune-mediated necroinflammatory reactions are an important cause of hepatocellular transformation during chronic hepatitis.
Cost effectiveness of enhanced recovery after surgery programme for vaginal hysterectomy: a comparison of pre and post‐implementation expenditures
Authors: Relph Sophie , Bell Alice , Sivashanmugarajan Viswapriya , Munro Kerry , Chigwidden Kelly , Lloyd Sue , Fakokunde Abiodun , Yoong Wai
Published: May 2013

Enhanced Recovery After Surgery programmes were first conceived to optimise perioperative patient care and have been delivered by surgical specialities in the UK for over a decade. Although their safety and acceptability have been ratified in many surgical fields including gynaecology and colorectal surgery, the cost effectiveness of its implementation in benign vaginal surgery remains unclear.

In this case‐control study, the perioperative expenditure for 45 women undergoing vaginal hysterectomy at a North London teaching hospital after implementation of an enhanced recovery pathway was compared with 45 matched controls prior to implementation.

Frequency of catheter use (84.4% vs. 95.6%) and median length of stay (23.5 vs. 42.9 h) were significantly lower following implementation of pathway (both p < 0.05). Although enhanced recovery patients were more likely to attend the accident and emergency department for minor symptoms following discharge (15.6% vs. 0%, p < 0.05), the inpatient readmission rate (6.7% vs. 0.0%, p > 0.05) was similar in both groups. Establishing the programme incurred additional expenditures including delivering a patient‐orientated gynaecology ‘school’ and employing a specialist enhanced recovery nurse, but despite these, we demonstrated a saving of 15.2% (or £164.86) per patient.

The cost efficiency savings, coupled with increased satisfaction and no rise in morbidity, offers a very attractive means of managing women undergoing vaginal hysterectomy. We believe that our data can be reproduced in other centres and recommend that the pathway be used routinely in women undergoing these procedures. Copyright © 2013 John Wiley & Sons, Ltd.
Familial risk of childhood cancer and tumors in the li‐fraumeni spectrum in the utah population database: Implications for genetic evaluation in pediatric practice
Authors: Curtin Karen , Smith Ken R. , Fraser Alison , Pimentel Richard , Kohlmann Wendy , Schiffman Joshua D.
Published: May 2013

We used the Utah Population Database to examine risk of cancer in relatives of 4,482 pediatric cancer cases (≤18 years old) diagnosed from 1966 to 2009 compared to matched population controls. We quantified cancer risk in relatives of children with cancer to determine evidence of familial aggregation and to inform risk assessment and counseling for families. Odds ratios that reflect risk were obtained using conditional logistic regression models adjusting for number of biological relatives, their degree of genetic relatedness and their person‐years at risk. First‐degree relatives (primarily siblings) of pediatric cases faced a twofold increased risk of a cancer diagnosis before age 19, which extended to their second‐degree relatives (p < 10−4, respectively). Furthermore, first‐degree relatives of children diagnosed before age 5 had a 3.6‐fold increased risk of developing pediatric cancer (p < 10−7), second‐degree relatives of very young (under age 5) cases were at 2.5‐fold risk (p < 10−4) and third‐degree relatives were at twofold risk (P < 10−3) of childhood cancer. Although first‐degree relatives of pediatric cases have a slight increased risk of adult tumors, when they do develop cancer they have a 1.7‐fold risk of developing a tumor in the Li‐Fraumeni spectrum. Our findings support the hypothesis of familial aggregation in pediatric cancer and suggest that a higher percent of childhood cancers may be related to hereditary syndromes than are adult cancers. We encourage the collection of a family medical history that is routinely updated for all pediatric cancer patients, and that families with early‐onset adult cancers or clusters of several cancers are referred for genetic counseling.
αv‐Integrin isoform expression in primary human tumors and brain metastases
Authors: Vogetseder Alexander , Thies Svenja , Ingold Barbara , Roth Patrick , Weller Michael , Schraml Peter , Goodman Simon L. , Moch Holger
Published: May 2013

To determine whether metastasis to brain is associated with altered expression patterns of integrins, we investigated the expression of αvβ3, αvβ5, αvβ6 and αvβ8 integrins in primary malignancies and metastases to brain of breast, lung and renal carcinomas and in malignant melanoma. Inhibitors of αv integrins are currently in clinical trials for glioblastoma. The role of integrins in the process of brain metastasis from other human tumors is unknown. Immunohistochemistry with novel integrin subtype specific rabbit monoclonal antibodies was performed on tissue microarrays of archival material of surgical biopsies taken from primary tumors and brain metastases. Integrin αvβ3 expression was increased in brain metastases compared to primary tumors of breast adenocarcinoma, non‐small cell lung cancer, renal clear cell cancer and malignant cutaneous melanoma (all p < 0.01). Similarly, integrin αvβ8 expression was increased in brain metastases compared to primary tumors of breast cancer (p < 0.0001), lung cancer (p < 0.01) and renal cancer (p < 0.0001), with a similar trend in metastatic melanoma. Integrin αvβ5 was expressed in most primary tumors (98% breast cancer; 67% lung cancer; 90% renal cancer; 89% melanoma) and showed a stronger expression in brain metastases compared to primary tumors from lung cancer and melanoma (p < 0.05). Also integrin αvβ6 expression was increased in brain metastases compared to primary breast cancer (p < 0.001). Conclusions: The stronger αv‐integrin expression in brain metastases, especially of αvβ3 and αvβ8 integrins, suggests that certain αv integrin are involved in the process of brain metastasis. αv Integrins may be therapeutic targets for patients with metastatic cancer in brain.
Multiobjective evolutionary algorithm with many tables for purely ab initio protein structure prediction
Authors: Brasil Christiane Regina Soares , Delbem Alexandre Claudio Botazzo , da Silva Fernando Luís Barroso
Published: May 2013

This article focuses on the development of an approach for ab initio protein structure prediction (PSP) without using any earlier knowledge from similar protein structures, as fragment‐based statistics or inference of secondary structures. Such an approach is called purely ab initio prediction. The article shows that well‐designed multiobjective evolutionary algorithms can predict relevant protein structures in a purely ab initio way. One challenge for purely ab initio PSP is the prediction of structures with β‐sheets. To work with such proteins, this research has also developed procedures to efficiently estimate hydrogen bond and solvation contribution energies. Considering van der Waals, electrostatic, hydrogen bond, and solvation contribution energies, the PSP is a problem with four energetic terms to be minimized. Each interaction energy term can be considered an objective of an optimization method. Combinatorial problems with four objectives have been considered too complex for the available multiobjective optimization (MOO) methods. The proposed approach, called “Multiobjective evolutionary algorithms with many tables” (MEAMT), can efficiently deal with four objectives through the combination thereof, performing a more adequate sampling of the objective space. Therefore, this method can better map the promising regions in this space, predicting structures in a purely ab initio way. In other words, MEAMT is an efficient optimization method for MOO, which explores simultaneously the search space as well as the objective space. MEAMT can predict structures with one or two domains with RMSDs comparable to values obtained by recently developed ab initio methods (GAPFCG, I‐PAES, and Quark) that use different levels of earlier knowledge. © 2013 Wiley Periodicals, Inc.
The Structures of Yttrium Iron Garnet/Gadolinium Gallium Garnet Superlattice Thin Films Studied by Synchrotron X‐Ray Surface Scattering
Authors: Lee Chih‐Hao , Liang Keng S. , Chern M. Y.
Published: May 2013

X‐ray measurements (specular and off‐specular X‐ray reflectivity, in‐plane and plane‐normal diffraction and truncation rod measurement) were carried out to characterize the epitaxial magnetic multilayers of yttrium iron garnet/gadolinium gallium garnet(GGG) on GGG substrate grown by the laser ablation deposition method. The perfection of the multilayer epitaxy can be better revealed in the observation of the 2nd harmonics of superlattice peaks in the reflectivity measurement, the forbidden diffraction peaks and the truncation rod measurement.
Prussian Blue Nanoparticles Self Assembling on Electrochemically Reduced Graphene Oxide Modified GC Electrode for Sensitive Hydrogen Peroxide Detection
Authors: Razmi Habib , Jabbari Mohammad , Mohammad‐Rezaei Rahim
Published: May 2013

A facile, fast, and convenient route was suggested for the fabrication of Prussian blue nano particles (PBNPs) assembled on reduced graphene oxide (RGO) modified glassy carbon electrode (PBNPs|RGO|GCE). RGO was electrodeposited on the surface of GCE and the prepared RGO|GCE was immersed into a ferric‐hexacyanoferrate(III) solution and PBNPs were assembled on the RGO|GCE for a certain period of time. The PBNPs film thickness can be easily controlled by adjusting the assembling duration. The developed PBNPs|RGO|GCE was successfully used for determining hydrogen peroxide, with a linear response over the concentration range 0.5‐400 μM, a good accuracy and precision, detection limit 0.44 μM, and sensitivity 1168 mA M−1 cm−2.
A Facile and Rapid Sonochemical Route to Synthesize Highly Ordered Mesoporous Silicas MCM‐48 and Al‐MCM‐48 with Ia3d Cubic Structure Using Gemini Surfactant
Authors: Wu Hao‐Yiang , Huang Shi‐Zhe , Ting Chun‐Chiang , Deka Juti Rani , Kao Hsien‐Ming
Published: May 2013

Highly ordered cubic mesoporous silicas MCM‐48 and Al‐MCM‐48 with high surface areas were successfully synthesized using Gemini surfactant as template under basic conditions within a very short time period with the aid of ultrasonic irradiation. The introduction of ultrasonic irradiation as an intermediate synthesis step before the hydrothermal treatment has reduced the total synthesis time significantly from 7 days to 24 hours, which is much shorter than the required time for the conventional synthesis of MCM‐48 directly via the hydrothermal route alone. The structural and textural properties of the resultant materials can be finely tuned by varying the ultrasonic irradiation time for pure MCM‐48 and Al‐MCM‐48 with various Si/Al ratios. The final products exhibited well ordered cubic Ia3d mesostructure with surface areas in the range of 968‐1861 m2g−1, pore volumes of 0.52‐0.91 cm3g−1, and pore diameters in the range of 1.9‐2.9 nm, which are comparable to the conventional analogues.
From Sumatra 2004 to Tohoku‐Oki 2011: The systematic GPS detection of the ionospheric signature induced by tsunamigenic earthquakes
Authors: Occhipinti Giovanni , Rolland Lucie , Lognonné Philippe , Watada Shingo
Published: May 2013

The recent tsunamigenic earthquake in Tohoku (11 March 2011) strongly affirms, one more time after the Sumatra event (26 December 2004), the necessity to open new paradigms in oceanic monitoring. Detection of ionospheric anomalies following the Sumatra tsunami demonstrated that ionosphere is sensitive to the tsunami propagation. Observations supported by modeling proved that tsunamigenic ionospheric anomalies are deterministic and reproducible by numerical modeling via the ocean/neutral‐atmosphere/ionosphere coupling mechanism. In essence, tsunami induces internal gravity waves propagating within the neutral atmosphere and detectable in the ionosphere. Most of the ionospheric anomalies produced by tsunamis were observed in the far field where the tsunami signature in the ionosphere is clearly identifiable. In this work, we highlight the early signature in the ionosphere produced by tsunamigenic earthquakes and observed by GPS, measuring the total electron content, close to the epicenter. We focus on the first hour after the seismic rupture. We demonstrate that acoustic‐gravity waves generated at the epicenter by the direct vertical displacement of the source rupture and the gravity wave coupled with the tsunami can be discriminated with theoretical support. We illustrate the systematic nature of those perturbations showing several observations: nominally the ionospheric perturbation following the tsunamigenic earthquakes in Sumatra on 26 December 2004 and 12 September 2007; in Chile on 14 November 2007; in Samoa on 29 September 2009; and the recent catastrophic Tohoku‐Oki event on 11 March 2011. Based on the analytical description, we provide tracks for further modeling efforts and clues for the interpretation of complex—and thus often misleading—observations. The routine detection of the early ionospheric anomalies following the rupture highlights the role of ionospheric sounding in the future ocean monitoring and tsunami detection.
Trends in ozone, its precursors, and related secondary oxidation products in Los Angeles, California: A synthesis of measurements from 1960 to 2010
Authors: Pollack Ilana B. , Ryerson Thomas B. , Trainer Michael , Neuman J. A. , Roberts James M. , Parrish David D.
Published: May 2013

Decreases in ozone (O3) observed in California's South Coast Air Basin (SoCAB) over the past five decades have resulted from decreases in local emissions of its precursors, nitrogen oxides (NOx = NO + NO2) and volatile organic compounds (VOCs). Ozone precursors have been characterized in the SoCAB with measurements dating back to 1960. Here we compile an extensive historical data set using measurements in the SoCAB between 1960 and 2010. Faster rates of decrease have occurred in abundances of VOCs (−7.3 ± 0.7% yr−1) than in NOx (−2.6 ± 0.3% yr−1), which have resulted in a decrease in VOC/NOx ratio (−4.8 ± 0.9% yr−1) over time. Trends in the NOx oxidation products peroxyacetyl nitrate (PAN) and nitric acid (HNO3), measured in the SoCAB since 1973, show changes in ozone production chemistry resulting from changes in precursor emissions. Decreases in abundances of PAN (−9.3 ± 1.1% yr−1) and HNO3 (−3.0 ± 0.8% yr−1) reflect trends in VOC and NOx precursors. Enhancement ratios of O3 to (PAN + HNO3) show no detectable trend in ozone production efficiency, while a positive trend in the oxidized fraction of total reactive nitrogen (+2.2 ± 0.5% yr−1) suggests that atmospheric oxidation rates of NOx have increased over time as a result of the emissions changes. Changes in NOx oxidation pathways have increasingly favored production of HNO3, a radical termination product associated with quenching the ozone formation cycle.
Medicane risk in a changing climate
Authors: Romero R. , Emanuel K.
Published: May 2013

Medicanes or “Mediterranean hurricanes” are extreme cyclonic windstorms morphologically and physically similar to tropical cyclones. Owing to their potential destructiveness on the islands and continental coastal zones, medicane risk assessment is of paramount importance. With an average frequency of only one to two events per year and given the lack of systematic, multidecadal databases, an objective evaluation of the long‐term risk of medicane‐induced winds is impractical with standard methods. Also, there is increasing concern about the way these extreme phenomena could change in frequency or intensity as a result of human influences on climate. Here we apply a statistical‐deterministic approach that entails the generation of thousands of synthetic storms, thus enabling a statistically robust assessment of the current and future risk. Fewer medicanes but a higher number of violent storms are projected at the end of the century compared to present, suggesting an increased probability of major economic and social impacts as the century progresses.
A validated assay by liquid chromatography–tandem mass spectrometry for the simultaneous quantification of elvitegravir and rilpivirine in HIV positive patients
Authors: Aouri Manel , Calmy Alexandra , Hirschel Bernard , Telenti Amalio , Buclin Thierry , Cavassini Matthias , Rauch Andri , Decosterd Laurent A.
Published: May 2013

Because of the large variability in the pharmacokinetics of anti‐HIV drugs, therapeutic drug monitoring in patients may contribute to optimize the overall efficacy and safety of antiretroviral therapy. An LC–MS/MS method for the simultaneous assay in plasma of the novel antiretroviral agents rilpivirine (RPV) and elvitegravir (EVG) has been developed to that endeavor. Plasma samples (100 μL) extraction is performed by protein precipitation with acetonitrile, and the supernatant is subsequently diluted 1:1 with 20‐mM ammonium acetate/MeOH 50:50. After reverse‐phase chromatography, quantification of RPV and EVG, using matrix‐matched calibration samples, is performed by electrospray ionization–triple quadrupole mass spectrometry by selected reaction monitoring detection using the positive mode. The stable isotopic‐labeled compounds RPV‐13C6 and EVG‐D6 were used as internal standards.

The method was validated according to FDA recommendations, including assessment of extraction yield, matrix effects variability (<6.4%), as well as EVG and RPV short and long‐term stability in plasma. Calibration curves were validated over the clinically relevant concentrations ranging from 5 to 2500 ng/ml for RPV and from 50 to 5000 ng/ml for EVG. The method is precise (inter‐day CV%: 3–6.3%) and accurate (3.8–7.2%). Plasma samples were found to be stable (<15%) in all considered conditions (RT/48 h, +4°C/48 h, −20°C/3 months and 60°C/1 h). Selected metabolite profiles analysis in patients' samples revealed the presence of EVG glucuronide, that was well separated from parent EVG, allowing to exclude potential interferences through the in‐source dissociation of glucuronide to parent drug. This new, rapid and robust LCMS/MS assay for the simultaneous quantification of plasma concentrations of these two major new anti‐HIV drugs EVG and RPV offers an efficient analytical tool for clinical pharmacokinetics studies and routine therapeutic drug monitoring service. Copyright © 2013 John Wiley & Sons, Ltd.
Chronic rhinosinusitis increased the risk of chronic periodontitis
Authors: Keller Joseph J. , Wu Chuan‐Song , Lin Herng‐Ching
Published: May 2013

Objectives/Hypothesis

Although chronic periodontitis (CP) and chronic rhinosinusitis (CRS) both share immunological disturbances as pathological factors, no prior study has investigated the risk for CP among patients with CRS. This study set out to provide an estimation of risk by utilizing a cohort study design to leverage the statistical power of a population‐based dataset in Taiwan.

Study Design

A retrospective cohort study.

Methods

In total, 13,782 CRS subjects were included in the study cohort and 41,346 subjects were randomly extracted for the comparison cohort. We individually tracked each subject in this study (N = 55,128) for a 5‐year period following their index date to identify those subjects who received a subsequent diagnosis of CP. Cox proportional hazards regression analysis was conducted to calculate the 5‐year risk of subsequent CP following a diagnosis of CRS among the sampled subjects.

Results

The incidence rate of CP during the 5‐year follow‐up period was 5.12 (95% confidence interval [CI], 4.95‐5.30) per 100 person‐years and 3.24 (95% CI, 3.17‐3.30) per 100 person‐years for the study and comparison cohort, respectively. Cox proportional hazards regression revealed that the hazard ratio for CP during the 5‐year follow‐up period for subjects with CRS was 1.59 times (95% CI, 1.52‐1.67) that of comparison subjects after adjusting for monthly income, geographic region, hypertension, diabetes, coronary heart disease, and hyperlipidemia, and censoring for cases who died during the 5‐year follow‐up period.

Conclusions

This study detected an increased risk for CP among patients suffering from CRS. CRS patients should be alerted to pay particular attention to their oral hygiene practices to prevent both CP and its downstream sequelae.
Rapid estimation of cartilage T2 with reduced T1 sensitivity using double echo steady state imaging
Authors: Heule Rahel , Ganter Carl , Bieri Oliver
Published: May 2013

Purpose

In principle, double echo steady state (DESS) offers morphological and quantitative T2 imaging of cartilage within one single scan. However, accurate T2 estimation is hampered by its prominent T1 dependency in the limit of low flip angles, generally used to image cartilage morphology, as for the osteoarthritis initiative. A new postprocessing approach is introduced to overcome this T1‐related bias for rapid DESS‐based T2 quantification in the low flip angle regime.

Methods

Based on a rough global T1 estimator and a golden section search, T2 is extracted from the ratio of the two echoes acquired with DESS. The new relaxometry method is evaluated from simulations and in vivo 3D measurements of the knee joint at 3T.

Results

A pronounced reduction in the T1‐related bias of DESS‐T2 estimation and increased zonal variation in T2 between deep and superficial cartilage layers are observed. The improvement becomes particularly evident in the range of low flip angles (α < 45°), commonly used for morphological DESS imaging.

Conclusion

Using a simple global T1 estimate, the reliability of DESS‐T2 quantification can be considerably increased. The results emphasize the potential of DESS to fuse accurate quantitative T2 and morphological imaging of the musculoskeletal system within one single scan. Magn Reson Med 71:1137–1143, 2014. © 2013 Wiley Periodicals, Inc.
Effect of interfacial interactions on the crystal growth rate in model PE/SiO2 nanocomposites: Comparing experiments with Lauritzen‐Hoffman model and MD simulation
Authors: Jancar J. , Balkova R.
Published: May 2013

Nanoparticles with engineered surface chemistry represent novel means in controlling the in‐situ formation of property‐specific supramolecular structure in advanced processing technologies of semicrystalline polymers. Often, the published experimental data on effects of interfacial adhesion on the crystallization kinetics of polymer nanocomposites report contradictory results even for similar systems. Computer simulations allow separating structural and test variables, thus, can provide useful framework for understanding these apparent controversies. Our MD simulation of Regime II crystallization showed that adding non‐nucleating spherical nanoparticles reduced the crystal growth rate, GII, compared with the neat polymer with the extent of the reduction proportional to the strength of interfacial attraction. It also suggested that, regardless of the strength of the interfacial interactions, additional reduction of the GII was caused by topological constraints imposed by nanoparticles on the stem attachment. Both the Lauritzen‐Hoffman model predicted and MD simulated GII reduction agreed fairly well with that obtained experimentally for monodisperse PE filled with nanometer‐sized SiO2. POLYM. ENG. SCI., 53:2696–2704, 2013. © 2013 Society of Plastics Engineers
Hierarchical Carbon‐Encapsulated Iron Nanoparticles as a Magnetically Separable Adsorbent for Removing Thiophene in Liquid Fuel
Authors: Yu Chang , Sun Yufeng , Fan Xiaoming , Zhao Zongbin , Qiu Jieshan
Published: May 2013

Hierarchical carbon‐encapsulated iron nanoparticles (Fe@Cs) with typical core/shell structure are successfully synthesized from starch and iron nitrate by an easy‐to‐handle process at different carbonization temperatures (600–1000 °C). The nanoparticles are characterized by transmission electron microscopy (TEM), X‐ray diffraction (XRD), nitrogen adsorption, and Fourier transform infrared spectroscopy (FTIR). The results show that the carbonization temperature has an important effect on the morphology, the core shape, the diameters, and the porous structure as well as performance of Fe@Cs. Fe@C samples carbonized at 900 °C (Fe@C‐900) show the relatively perfect quasi‐spherical bcc‐Fe core/carbon shell porous structure and their diameters are in a narrow range of 20–50 nm. The adsorption capabilities of Fe@C samples obtained at different carbonization temperatures for removal of thiophene from model oils are evaluated and compared in a batch‐type adsorption system. It has been found that among all of the samples measured, Fe@C‐900 shows the highest adsorption capability with an increase of 54% for thiophene in comparison with that of the commercial activated carbon. The feasibility of the as‐prepared Fe@C‐900 as a magnetically separable adsorbent is also demonstrated.
Role of loops connecting secondary structure elements in the stabilization of proteins isolated from thermophilic organisms
Authors: Balasco Nicole , Esposito Luciana , Simone Alfonso De , Vitagliano Luigi
Published: May 2013

It has been recently discovered that the connection of secondary structure elements (ββ‐unit, βα‐ and αβ‐units) in proteins follows quite stringent principles regarding the chirality and the orientation of the structural units (Koga et al., Nature 2012;491:222–227). By exploiting these rules, a number of protein scaffolds endowed with a remarkable thermal stability have been designed (Koga et al., Nature 2012;491:222–227). By using structural databases of proteins isolated from either mesophilic or thermophilic organisms, we here investigate the influence of supersecondary associations on the thermal stability of natural proteins. Our results suggest that β‐hairpins of proteins from thermophilic organisms are very frequently characterized by shortenings of the loops. Interestingly, this shortening leads to states that display a very strong preference for the most common connectivity of the strands observed in native protein hairpins. The abundance of selective states in these proteins suggests that they may achieve a high stability by adopting a strategy aimed to reduce the possible conformations of the unfolded ensemble. In this scenario, our data indicate that the shortening is effective if it increases the adherence to these rules. We also show that this mechanism may operate in the stabilization of well‐known protein folds (thioredoxin and RNase A). These findings suggest that future investigations aimed at defining mechanism of protein stabilization should also consider these effects.
Functional studies of N‐terminally modified CYP2J2 epoxygenase in model lipid bilayers
Authors: McDougle Daniel R. , Palaria Amrita , Magnetta Eric , Meling Daryl D. , Das Aditi
Published: May 2013

CYP2J2 epoxygenase is a membrane bound cytochrome P450 that converts omega‐3 and omega‐6 fatty acids into physiologically active epoxides. In this work, we present a comprehensive comparison of the effects of N‐terminal modifications on the properties of CYP2J2 with respect to the activity of the protein in model lipid bilayers using Nanodiscs. We demonstrate that the complete truncation of the N‐terminus changes the association of this protein with the E.coli membrane but does not disrupt incorporation in the lipid bilayers of Nanodiscs. Notably, the introduction of silent mutations at the N‐terminus was used to express full length CYP2J2 in E. coli while maintaining wild‐type functionality. We further show that lipid bilayers are essential for the productive use of NADPH for ebastine hydroxylation by CYP2J2. Taken together, it was determined that the presence of the N‐terminus is not as critical as the presence of a membrane environment for efficient electron transfer from cytochrome P450 reductase to CYP2J2 for ebastine hydroxylation in Nanodiscs. This suggests that adopting the native‐like conformation of CYP2J2 and cytochrome P450 reductase in lipid bilayers is essential for effective use of reducing equivalents from NADPH for ebastine hydroxylation.
Effects of the Fc‐III tag on activity and stability of green fluorescent protein and human muscle creatine kinase
Authors: Feng Shan , Gong Yiyi , Adilijiang Gulishana , Deng Haiteng
Published: May 2013

The Fc‐III tag is a newly developed fusion tag that can be applied to protein purification and detection. In the present work, we use the Fc‐III‐tagged green fluorescent protein (GFP) and human muscle creatine kinase (CK) as model systems to investigate effects of the Fc‐III tag on activities and stabilities of the expressed multicysteine‐containing proteins. Our results show the Fc‐III tag has no adverse effects on the fluorescence of GFP and reduces the occurrence of GFP misfolding due to incorrect Cys oxidation compared with the His‐tagged protein. The activity and stability of the Fc‐III‐tagged CK is slightly lower than that of the tag‐free CK, but is higher than that of the His‐tagged CK as determined by the ratio of the oxidized versus reduced CK. A major portion of His‐tagged CK is in its oxidized form, while that of the Fc‐III‐tagged CK is in its reduced form. A folding model of CK with different tags was proposed, which may provide insights into the effect of the Fc‐III tag on the conformations of disulfide‐bridged proteins.
Understanding large text corpora via sparse machine learning
Authors: El Ghaoui Laurent , Pham Vu , Li Guan‐Cheng , Duong Viet‐An , Srivastava Ashok , Bhaduri Kanishka
Published: May 2013

Sparse machine learning has recently emerged as powerful tool to obtain models of high‐dimensional data with high degree of interpretability, at low computational cost. The approach has been successfully used in many areas, such as signal and image processing. This article posits that these methods can be extremely useful in the analysis of large collections of text documents, without requiring user expertise in machine learning. Our approach relies on three main ingredients: (i) multidocument text summarization; (ii) comparative summarization of two corpora, both using sparse regression or classification; (iii) sparse principal components and sparse graphical models for unsupervised analysis and visualization of large text corpora. We validate our methods using a corpus of Aviation Safety Reporting System (ASRS) reports and demonstrate that the methods can reveal causal and contributing factors in runway incursions. Furthermore, we show that the methods automatically discover four main tasks that pilots perform during flight, which can aid in further understanding the causal and contributing factors to runway incursions and other drivers for aviation safety incidents. We also provide a comparative study involving other commonly used datasets, and report on the competitiveness of sparse machine learning compared to state‐of‐the‐art methods such as latent Dirichlet allocation (LDA). © 2013 Wiley Periodicals, Inc. Statistical Analysis and Data Mining 6: 221–242, 2013
Logistic‐AFT location‐scale mixture regression models with nonsusceptibility for left‐truncated and general interval‐censored data
Authors: Chen Chen‐Hsin , Tsay Yuh‐Chyuan , Wu Ya‐Chi , Horng Cheng‐Fang
Published: May 2013

In conventional survival analysis there is an underlying assumption that all study subjects are susceptible to the event. In general, this assumption does not adequately hold when investigating the time to an event other than death. Owing to genetic and/or environmental etiology, study subjects may not be susceptible to the disease. Analyzing nonsusceptibility has become an important topic in biomedical, epidemiological, and sociological research, with recent statistical studies proposing several mixture models for right‐censored data in regression analysis. In longitudinal studies, we often encounter left, interval, and right‐censored data because of incomplete observations of the time endpoint, as well as possibly left‐truncated data arising from the dissimilar entry ages of recruited healthy subjects. To analyze these kinds of incomplete data while accounting for nonsusceptibility and possible crossing hazards in the framework of mixture regression models, we utilize a logistic regression model to specify the probability of susceptibility, and a generalized gamma distribution, or a log‐logistic distribution, in the accelerated failure time location‐scale regression model to formulate the time to the event. Relative times of the conditional event time distribution for susceptible subjects are extended in the accelerated failure time location‐scale submodel. We also construct graphical goodness‐of‐fit procedures on the basis of the Turnbull–Frydman estimator and newly proposed residuals. Simulation studies were conducted to demonstrate the validity of the proposed estimation procedure. The mixture regression models are illustrated with alcohol abuse data from the Taiwan Aboriginal Study Project and hypertriglyceridemia data from the Cardiovascular Disease Risk Factor Two‐township Study in Taiwan. Copyright © 2013 John Wiley & Sons, Ltd.
Improved Cell Therapy Protocols for Parkinson's Disease Based on Differentiation Efficiency and Safety of hESC-, hiPSC-, and Non-Human Primate iPSC-Derived Dopaminergic Neurons
Authors: Sundberg Maria , Bogetofte Helle , Lawson Tristan , Jansson Johan , Smith Gaynor , Astradsson Arnar , Moore Michele , Osborn Teresia , Cooper Oliver , Spealman Roger , Hallett Penelope , Isacson Ole
Published: May 2013

The main motor symptoms of Parkinson's disease are due to the loss of dopaminergic (DA) neurons in the ventral midbrain (VM). For the future treatment of Parkinson's disease with cell transplantation it is important to develop efficient differentiation methods for production of human iPSCs and hESCs-derived midbrain-type DA neurons. Here we describe an efficient differentiation and sorting strategy for DA neurons from both human ES/iPS cells and non-human primate iPSCs. The use of non-human primate iPSCs for neuronal differentiation and autologous transplantation is important for preclinical evaluation of safety and efficacy of stem cell-derived DA neurons. The aim of this study was to improve the safety of human- and non-human primate iPSC (PiPSC)-derived DA neurons. According to our results, NCAM+/CD29low sorting enriched VM DA neurons from pluripotent stem cell-derived neural cell populations. NCAM+/CD29low DA neurons were positive for FOXA2/TH and EN1/TH and this cell population had increased expression levels of FOXA2, LMX1A, TH, GIRK2, PITX3, EN1, NURR1 mRNA compared to unsorted neural cell populations. PiPSC-derived NCAM+/CD29low DA neurons were able to restore motor function of 6-hydroxydopamine (6-OHDA) lesioned rats 16 weeks after transplantation. The transplanted sorted cells also integrated in the rodent brain tissue, with robust TH+/hNCAM+ neuritic innervation of the host striatum. One year after autologous transplantation, the primate iPSC-derived neural cells survived in the striatum of one primate without any immunosuppression. These neural cell grafts contained FOXA2/TH-positive neurons in the graft site. This is an important proof of concept for the feasibility and safety of iPSC-derived cell transplantation therapies in the future.
Polycomb Determines Responses to Smad2/3 Signaling in Embryonic Stem Cell Differentiation and in Reprogramming
Authors: Dahle Øyvind , Kuehn Michael R.
Published: May 2013

Integration of extrinsic signals, epigenetic regulators, and intrinsic transcription factors establishes pluripotent stem cell identity. Interplay between these components also underlies the capacity of stem cells to undergo differentiation, and of differentiated cells to re-establish the pluripotent state in direct reprogramming. Polycomb repressive complexes are epigenetic regulators that play key roles in stem cell identity and in differentiated cell fates. Smad2 and Smad3 (Smad2/3), the intracellular mediators of the Nodal/Activin/transforming growth factor (TGF) β cell-cell signaling pathway also are implicated in stem cell pluripotency and in differentiation. Here, we show that Polycomb imposes responses to Smad2/3-mediated signaling to selectively regulate expression of the master pluripotency factor Oct4 during initiation of differentiation, but not in the self-renewing pluripotent ground state. During reprogramming back to the ground state, we find that the enhancement of reprogramming efficiency stemming from blocking Nodal/Activin/TGFβ signaling also depends on Polycomb. These context-dependent responses to Smad2/3 imposed by Polycomb action provide a mechanism for selective gene regulation that can reconcile the apparently conflicting roles of this signaling pathway in pluripotency, differentiation, and reprogramming.
Evolving graph‐based chromosome by means of variable size genetic network programming with binomial distribution
Authors: Li Bing , Li Xianneng , Mabu Shingo , Hirasawa Kotaro
Published: May 2013

Genetic network programming (GNP) is a graph‐based evolutionary algorithm with fixed size, which has been proven to solve complicated problems efficiently and effectively. In this paper, variable size genetic network programming (GNPvs) with binomial distribution has been proposed, which will change the size of the individuals and obtain their optimal size during evolution. The proposed method will select the number of nodes to move from one parent GNP to another parent GNP during crossover to implement the new feature of GNP. The probability of selecting the number of nodes to move satisfies a binomial distribution. The proposed method can keep the effectiveness of crossover, improve the performance of GNP, and find the optimal size of the individuals. The well‐known testbed Tileworld is used to show the numerical results in the simulations. © 2013 Institute of Electrical Engineers of Japan. Published by John Wiley & Sons, Inc.
In silico applications of bioisosterism in contemporary medicinal chemistry practice
Authors: Papadatos George , Brown Nathan
Published: May 2013

Bioisosterism is a key concept in medicinal chemistry, as it allows medicinal chemists to interchange structural fragments without significant perturbation in biological activity. Not surprisingly, given the vast amount of bioactivity data and chemoinformatics resources now available, there has been a significant surge in the number of computational approaches available to mine and identify bioisosteric replacements for fragments of bioactive compounds. Such methods have certainly provided medicinal chemists with a diverse arsenal of in‐house, commercial, and academic tools and interfaces to aid in the optimization across a number of end points such as bioactivity; selectivity; and absorption, distribution, metabolism, excretion, and toxicity properties for effective and efficient drug design. These in silico bioisosteric replacement mining approaches can generally be divided into two categories, namely ligand based and structure based. The approaches of the former category use information that is derived from ligands, whereas the latter category requires knowledge of the biological target, as well as specific knowledge of the interactions between ligand and target in the binding pocket. Ligand‐based methodologies are also typically divided into similarity‐based and database mining (or knowledge‐based) approaches. In general, the former provide an assessment of putative bioisosteric fragments and substructures, in terms of molecular topology and descriptors, whereas the latter extract structural transformations from large chemical repositories and associate them with the induced change in biological or any other property of interest. Following systematic retrospective studies, a large number of nonclassical bioisosteric equivalents have been reported in the literature.

This article is categorized under:

Computer and Information Science > Chemoinformatics
Domestic dog hair samples as biomarkers of arsenic contamination
Authors: Vázquez C. , Palacios O. , Boeykens S. , Marcó Parra L. M.
Published: May 2013

Hair arsenic concentrations were measured in 50 dogs living at Barrio Los Alamos, Gran Buenos Aires, Argentina, to evaluate the contamination risk in humans living in an area with arsenic levels higher than maximum allowed limit of 10 µg l−1. This region belongs to the zone in Argentina with Chronic Endemic Hydroarsenicism. Quantification of the samples was carried out using total reflection X‐ray fluorescence technique after a sample preparation procedure. Independent of genre, age and breed, hair dogs from Los Alamos had significantly higher arsenic concentrations than a set of ten dogs used as blank coming from a free arsenic area. These found levels in hair indicated a chronic contamination in dogs and suggest similar presumption in humans. Results of this study encourage the potential of using pets as biomarkers of environmental metal contamination. Copyright © 2013 John Wiley & Sons, Ltd.
Synthesis and Molecular Structure of the New Green Emitting Complex [Ir2(μ2‐oxamidato‐N,N′,O,O′)(2‐(p‐tolyl)pyridinato)4]
Authors: Graf Marion , Czerwieniec Rafał , Sünkel Karlheinz
Published: May 2013

The reaction of the complex [{Ir(μ‐Cl)(ptpy)2}2] (1) with oxamide in methanol in the presence of sodium methylate as the base was investigated. During the reaction the new complex [Ir2(μ2‐oxamidato‐N,N′,O,O′)(ptpy)4] (2), ptpy = 2‐(p‐tolyl)pyridinato was obtained. The molecular structure of compound 2 was determined by an X‐ray diffraction study. 2 crystallized from dichloromethane/methanol as a dihydrate in the orthorhombic space group Pbcm. This new compound displays intense green phosphorescence, with φPL = 60 %, stemming from the lowest triplet state of the 3MLCT/LC character.
Rhomboid domain containing 1 inhibits cell apoptosis by upregulating AP‐1 activity and its downstream target Bcl‐3
Authors: Ren Xiaoxia , Song Wei , Liu Wenjie , Guan Xin , Miao Fei , Miao Shiying , Wang Linfang
Published: May 2013

We have previously reported that rhomboid domain containing 1 (RHBDD1), a new member of the Rhomboid family, is highly expressed in testis. In the present work, luciferase analyses showed that RHBDD1 enhanced the AP‐1 activity in a dose‐ and activity‐dependent manner. RHBDD1 overexpression increased c‐Jun activity, and the activity was visibly inhibited when RHBDD1 was knocked down. The suppression of c‐Jun by inactivation of RHBDD1 was rescued by overexpressing RHBDD1. However, c‐Jun overexpression did not alter the expression level of RHBDD1. Furthermore, knockdown of RHBDD1 led to increased cell apoptosis and reduced expression of Bcl‐3. Our findings indicate that RHBDD1 could inhibit cell apoptosis by activating and upregulating c‐Jun and its downstream target, Bcl‐3.
The pH sensitivity of H2O2 metabolism in skeletal muscle mitochondria
Authors: Banh Sheena , Treberg Jason R.
Published: May 2013

Mitochondria have the capacity to produce and consume H2O2. We examined H2O2 metabolism in isolated rat skeletal muscle mitochondria and found that the substrate‐dependent capacity to consume extramitochondrial H2O2 was markedly higher than the observed rate of H2O2 efflux from mitochondria under the same conditions. The substrate‐dependent capacity to consume H2O2 was sensitive to the pH of the medium and we propose that pH related differences in H2O2 consumption pathways may explain inconsistencies we observed between H2O2 efflux rate and the reduction state of the matrix NADH pool.
Progranulin deficiency exaggerates, whereas progranulin‐derived Atsttrin attenuates, severity of dermatitis in mice
Authors: Zhao Yun-Peng , Tian Qing-Yun , Liu Chuan-Ju
Published: May 2013

PGRN and its derived engineered protein, Atsttrin, were reported to antagonize TNFα and protect against inflammatory arthritis [Tang, W. et al. (2011) The growth factor progranulin binds to TNF receptors and is therapeutic against inflammatory arthritis in mice. Science 332 (6028) 478–484]. Here we found that PGRN level was also significantly elevated in skin inflammation. PGRN−/− mice exhibited more severe inflammation following induction of oxazolone (OXA). In contrast, recombinant Atsttrin protein effectively attenuated inflammation in mice dermatitis model. In addition, the protective role of PGRN and Atsttrin in dermatitis was probably due to their inhibition on NF‐κB signaling. Collectively, PGRN, especially its derived engineered protein, Atsttrin, may represent a potential molecular target for prevention and treatment of inflammatory skin diseases.
CXCL14 is a natural inhibitor of the CXCL12–CXCR4 signaling axis
Authors: Tanegashima Kosuke , Suzuki Kenji , Nakayama Yuki , Tsuji Kohei , Shigenaga Akira , Otaka Akira , Hara Takahiko
Published: May 2013

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