bluuebunny/crossref_metadata_2025 huggingface dataset:
Hedgehog signaling regulates dental papilla formation and tooth size during zebrafish odontogenesis
Authors: Yu Jeffrey C. , Fox Zachary D. , Crimp James L. , Littleford Hana E. , Jowdry Andrea L. , Jackman William R.
Published: February 2015

Background: Intercellular communication by the hedgehog cell signaling pathway is necessary for tooth development throughout the vertebrates, but it remains unclear which specific developmental signals control cell behavior at different stages of odontogenesis. To address this issue, we have manipulated hedgehog activity during zebrafish tooth development and visualized the results using confocal microscopy. Results: We first established that reporter lines for dlx2b, fli1, NF‐κB, and prdm1a are markers for specific subsets of tooth germ tissues. We then blocked hedgehog signaling with cyclopamine and observed a reduction or elimination of the cranial neural crest derived dental papilla, which normally contains the cells that later give rise to dentin‐producing odontoblasts. Upon further investigation, we observed that the dental papilla begins to form and then regresses in the absence of hedgehog signaling, through a mechanism unrelated to cell proliferation or apoptosis. We also found evidence of an isometric reduction in tooth size that correlates with the time of earliest hedgehog inhibition. Conclusions: We hypothesize that these results reveal a previously uncharacterized function of hedgehog signaling during tooth morphogenesis, regulating the number of cells in the dental papilla and thereby controlling tooth size. Developmental Dynamics 244:577–590, 2015. © 2015 Wiley Periodicals, Inc.
Telomere length and outcomes in ischaemic heart failure: data from the COntrolled ROsuvastatin multiNAtional Trial in Heart Failure (CORONA)
Authors: Haver Vincent G. , Mateo Leach Irene , Kjekshus John , Fox Jayne C. , Wedel Hans , Wikstrand John , de Boer Rudolf A. , van Gilst Wiek H. , McMurray John J.V. , van Veldhuisen Dirk J. , van der Harst Pim
Published: February 2015

Aims

Leucocyte telomere length is considered a marker of biological ageing and has been suggested to be shorter in patients with CAD and heart failure compared with healthy controls. The aim of this study was to determine whether telomere length is associated with clinical outcomes in patients with ischaemic heart failure and whether this association is superior to chronological age as defined by date of birth.

Methods and results

We measured leucocyte telomere length in 3275 patients with chronic ischaemic systolic heart failure participating in the COntrolled ROsuvastatin multiNAtional Trial in Heart Failure (CORONA) study. The primary composite endpoint was cardiovascular death, non‐fatal myocardial infarction, and non‐fatal stroke, which occurred in 575 patients during follow‐up. We observed a significant association of leucocyte telomere lengths with the primary endpoint (hazard ratio 1.10; 95% confidence interval 1.01–1.20; P = 0.03). However, this observation was not superior to age as defined by date of birth. The neutral effect of rosuvastatin treatment on clinical outcomes was not modified by baseline telomere length.

Conclusion

Biological age as defined by leucocyte telomere length was associated with clinical outcomes in patients with ischaemic heart failure, but this association did not add prognostic information above age as defined by date of birth.
An entrainment model for non‐uniform sediment
Authors: Elhakeem Mohamed , Sattar Ahmed M. A.
Published: February 2015

A model was developed for the prediction of the entrainment rate of non‐uniform sediment considering the movement of bedforms. Laboratory experiments were conducted to advance the formulations of the proposed model and to validate and estimate the model parameters. The model parameters were related to the hydraulic conditions of the flow and the properties of the sediment mixtures using dimensional analysis and gene expression programming. The model incorporated four parameters on its formulation, namely the Shields stress and critical Shields stress to describe the hydraulic and sediment conditions of the flow, the Kramer coefficient of uniformity to describe the grain size distribution of a particular sediment mixture, and the relative position of a particular grain size fraction to the geometric mean to describe the entrainment rate of that fraction within the sediment mixture. The proposed model provided satisfactorily predictions with a deviation less than 25% between the measured and predicted values for most of the fractions, which confirms the validity of the proposed approach and model in predicting of the entrainment rates of various fractions. The model predictions were also compared with other models available for the prediction of the entrainment rate of non‐uniform sediment. The model predictions were within the same order of magnitude of the other models’ predictions. Copyright © 2015 John Wiley & Sons, Ltd.
Increase in mercury in Pacific yellowfin tuna
Authors: Drevnick Paul E. , Lamborg Carl H. , Horgan Martin J.
Published: February 2015

Mercury is a toxic trace metal that can accumulate to levels that threaten human and environmental health. Models and empirical data suggest that humans are responsible for a great deal of the mercury actively cycling in the environment at present. Thus, one might predict that the concentration of mercury in fish should have increased dramatically since the Industrial Revolution. Evidence in support of this hypothesis has been hard to find, however, and some studies have suggested that analyses of fish show no change in mercury concentration. By compiling and re-analyzing published reports on yellowfin tuna (Thunnus albacares) caught near Hawaii (USA) over the past half century, the authors found that the concentration of mercury in these fish currently is increasing at a rate of at least 3.8% per year. This rate of increase is consistent with a model of anthropogenic forcing on the mercury cycle in the North Pacific Ocean and suggests that fish mercury concentrations are keeping pace with current loading increases to the ocean. Future increases in mercury in yellowfin tuna and other fishes can be avoided by reductions in atmospheric mercury emissions from point sources. Environ Toxicol Chem 2015;34:931–934. © 2015 SETAC
On the Difficulty of Measuring Forecasting Skill in Financial Markets
Authors: Satchell Stephen E. , Williams Oliver J.
Published: February 2015

The use of correlation between forecasts and actual returns is commonplace in the literature, often used as a measurement of investors' skill. A prominent application of this is the concept of the information coefficient (IC). Not only can the IC be used as a tool to rate analysts and fund managers but it also represents an important parameter in the asset allocation and portfolio construction process. Nevertheless, a theoretical understanding of it has typically been limited to the partial equilibrium context where the investing activities of each agent have no effect on other market participants. In this paper we show that this can be an undesirable oversimplification and we demonstrate plausible circumstances in which conventional empirical measurements of IC can be highly misleading. We suggest that improved understanding of IC in a general equilibrium setting can lead to refined portfolio decision making ex ante and more informative analysis of performance ex post. Copyright © 2015 John Wiley & Sons, Ltd.
Last Night a Shrinkage Saved My Life: Economic Growth, Model Uncertainty and Correlated Regressors
Authors: Hofmarcher Paul , Crespo Cuaresma Jesús , Grün Bettina , Hornik Kurt
Published: February 2015

We compare the predictive ability of Bayesian methods which deal simultaneously with model uncertainty and correlated regressors in the framework of cross‐country growth regressions. In particular, we assess methods withspike and slabpriors combined with different prior specifications for the slope parameters in the slab. Our results indicate that moving away from Gaussiang‐priors towards Bayesian ridge, LASSO or elastic net specifications has clear advantages for prediction when dealing with datasets of (potentially highly) correlated regressors, a pervasive characteristic of the data used hitherto in the econometric literature. Copyright © 2015 John Wiley & Sons, Ltd.
Predictors of survival in patients with advanced hepatocellular carcinoma who permanently discontinued sorafenib
Authors: Iavarone Massimo , Cabibbo Giuseppe , Biolato Marco , Della Corte Cristina , Maida Marcello , Barbara Marco , Basso Michele , Vavassori Sara , Craxì Antonio , Grieco Antonio , Cammà Carlo , Colombo Massimo
Published: February 2015

Treatment with sorafenib of patients with advanced hepatocellular carcinoma is challenged by anticipated discontinuation due to tumor progression, liver decompensation, or adverse effects. While postprogression survival is clearly determined by the pattern of tumor progression, understanding the factors that drive prognosis in patients who discontinued sorafenib for any reason may help to improve patient management and second‐line trial design. Patients consecutively admitted to three referral centers who were receiving best supportive care following permanent discontinuation of sorafenib for any reason were included. Postsorafenib survival (PSS) was calculated from the last day of treatment to death or last visit available. Two hundred and sixty patients were included in this prospective study, aged 67 years, 60% with hepatitis C, 51% Child‐Pugh A, 83% performance status (PS) ≥1, 41% with macroscopic vascular invasion, and 38% with extrahepatic tumor spread. Overall, median PSS was 4.1 (3.3‐4.9) months, resulting from 4.6 (3.3‐5.7) months for 123 progressors, 7.3 (6.0‐10.0) months in 77 with adverse effects, and 1.8 (1.6‐2.4) months in 60 decompensated patients (P < 0.001). Postsorafenib survival was independently predicted by PS, prothrombin time, extrahepatic tumor spread, macrovascular invasion, and reason for discontinuation. Two hundred patients potentially eligible for second‐line therapy had a PSS of 5.3 (4.6‐7.1) months, which was dependent on reasons of discontinuation (P = 0.004), PS (P < 0.001), macrovascular invasion (P < 0.001), and extrahepatic metastases (P < 0.002). Conclusion: Discontinuation due to adverse effects in the absence of macrovascular invasion, extrahepatic metastases, and deteriorated PS predicts the best PSS in compensated patients, thereby setting the stage for both improved patient counseling and selection for second‐line therapy. (Hepatology 2015;62:784–791)
DNA methylation‐based prognosis and epidrivers in hepatocellular carcinoma
Authors: Villanueva Augusto , Portela Anna , Sayols Sergi , Battiston Carlo , Hoshida Yujin , Méndez‐González Jesús , Imbeaud Sandrine , Letouzé Eric , Hernandez‐Gea Virginia , Cornella Helena , Pinyol Roser , Solé Manel , Fuster Josep , Zucman‐Rossi Jessica , Mazzaferro Vincenzo , Esteller Manel , Llovet Josep M. ,   on behalf of the HEPTROMIC Consortium
Published: February 2015

Epigenetic deregulation has emerged as a driver in human malignancies. There is no clear understanding of the epigenetic alterations in hepatocellular carcinoma (HCC) and of the potential role of DNA methylation markers as prognostic biomarkers. Analysis of tumor tissue from 304 patients with HCC treated with surgical resection allowed us to generate a methylation‐based prognostic signature using a training‐validation scheme. Methylome profiling was done with the Illumina HumanMethylation450 array (Illumina, Inc., San Diego, CA), which covers 96% of known cytosine‐phosphate‐guanine (CpG) islands and 485,000 CpG, and transcriptome profiling was performed with Affymetrix Human Genome U219 Plate (Affymetrix, Inc., Santa Clara, CA) and miRNA Chip 2.0. Random survival forests enabled us to generate a methylation signature based on 36 methylation probes. We computed a risk score of mortality for each individual that accurately discriminated patient survival both in the training (221 patients; 47% hepatitis C–related HCC) and validation sets (n = 83; 47% alcohol‐related HCC). This signature correlated with known predictors of poor outcome and retained independent prognostic capacity of survival along with multinodularity and platelet count. The subset of patients identified by this signature was enriched in the molecular subclass of proliferation with progenitor cell features. The study confirmed a high prevalence of genes known to be deregulated by aberrant methylation in HCC (e.g., Ras association [RalGDS/AF‐6] domain family member 1, insulin‐like growth factor 2, and adenomatous polyposis coli) and other solid tumors (e.g., NOTCH3) and describes potential candidate epidrivers (e.g., septin 9 and ephrin B2). Conclusions: A validated signature of 36 DNA methylation markers accurately predicts poor survival in patients with HCC. Patients with this methylation profile harbor messenger RNA–based signatures indicating tumors with progenitor cell features. (Hepatology 2015;61:1945–1956)
Age and Assessments of Disability Accommodation Request Normative Appropriateness
Authors: Baldridge David C. , Swift Michele L.
Published: February 2015

In the United States, the labor force continues to age. As age increases, so does the likeliness of needing disability accommodation. Prior research indicates that people with disabilities often do not request needed accommodations when they assess that others at work would perceive a request as normatively inappropriate. Little, however, is currently known about the impact of age on these assessments. In this study, we integrate prior research on age, disability, social identity, and climate to propose and then test a model of the relationship between requesters’ age and their normative assessments using survey data from 242 people who became hearing impaired prior to entering the workforce. As hypothesized, requester age was negatively associated with normative appropriateness assessment favorability. Moreover, this negative influence was stronger in for‐profit organizational contexts and in workgroup contexts in which the requester lacked a coworker with a disability. Having a coworker with a similar disability also partially mediated the moderating effect of organization type on the association between age and normative appropriateness assessment favorability. Implications for research and practice are discussed. © 2015 Wiley Periodicals, Inc.
High‐frequency water quality monitoring in an urban catchment: hydrochemical dynamics, primary production and implications for the Water Framework Directive
Authors: Halliday Sarah J. , Skeffington Richard A. , Wade Andrew J. , Bowes Michael J. , Gozzard Emma , Newman Jonathan R. , Loewenthal Matthew , Palmer‐Felgate Elizabeth J. , Jarvie Helen P.
Published: February 2015

This paper describes the hydrochemistry of a lowland, urbanised river‐system, The Cut in England, using in situ sub‐daily sampling. The Cut receives effluent discharges from four major sewage treatment works serving around 190 000 people. These discharges consist largely of treated water, originally abstracted from the River Thames and returned via the water supply network, substantially increasing the natural flow. The hourly water quality data were supplemented by weekly manual sampling with laboratory analysis to check the hourly data and measure further determinands. Mean phosphorus and nitrate concentrations were very high, breaching standards set by EU legislation. Although 56% of the catchment area is agricultural, the hydrochemical dynamics were significantly impacted by effluent discharges which accounted for approximately 50% of the annual P catchment input loads and, on average, 59% of river flow at the monitoring point. Diurnal dissolved oxygen data demonstrated high in‐stream productivity. From a comparison of high frequency and conventional monitoring data, it is inferred that much of the primary production was dominated by benthic algae, largely diatoms. Despite the high productivity and nutrient concentrations, the river water did not become anoxic, and major phytoplankton blooms were not observed. The strong diurnal and annual variation observed showed that assessments of water quality made under the Water Framework Directive (WFD) are sensitive to the time and season of sampling. It is recommended that specific sampling time windows be specified for each determinand, and that WFD targets should be applied in combination to help identify periods of greatest ecological risk. © 2015 The Authors. Hydrological Processes published by John Wiley & Sons Ltd.
Osteoderm histology of Proterochampsia and Doswelliidae (Reptilia: Archosauriformes) and their evolutionary and paleobiological implications
Authors: Cerda Ignacio A. , Desojo Julia B. , Trotteyn María J. , Scheyer Torsten M.
Published: February 2015

Postcranial osteoderms are commonly developed in the major lineages of Archosauriformes, including forms such as proterochampsids and doswelliids. Here, we survey the histology of osteoderms of the doswelliids Archeopelta arborensis and Tarjadia ruthae, and the proterochampsids Chanaresuchus bonapartei and Pseudochampsa ischigualastensis to understand better the morphogenesis of these skeletal elements. Whereas, the Doswelliid osteoderms possess a trilaminar organization, in which two cortices (external and basal) can be differentiated from an internal core of cancellous bone, these elements are compact structures in proterochampsids. The osteoderms of P. ischigualastensis are avascular and they consist entirely of parallel‐fibered bone. Conversely, the osteoderms of C. bonapartei are well vascularized structures composed of zones of woven‐fibered bone and annuli of parallel‐fibered bone. The rather simple microstructure observed in P. ischigualastensis osteoderms suggests that these elements grew at a constant, low rate. Compared with proterochampsids, doswelliid osteoderms possess a more complex histology, which appears to be linked to variations in the growth rate during the osteoderm formation and also to the development of the external ornamentation. A comparison of our findings with the results of earlier studies on other archosauriforms (phytosaurs and pseudosuchians) reveals that the general osteoderm histology of doswelliids bears a closer resemblance to that of phytosaurs and pseudosuchians than the proterochampsid osteoderm microstructure. If all archosauriform osteoderms are homologous structures, the closer resemblance of doswellid osteoderm microstructures to that of phytosaurs and pseudosuchians is in agreement with the hypothesis that doswellids are more closely related to archosaurs than proterochampsids. J. Morphol. 276:385–402, 2015. © 2015 Wiley Periodicals, Inc.
Assessment of whole spine vertebral bone marrow fat using chemical shift‐encoding based water‐fat MRI
Authors: Baum Thomas , Yap Samuel P. , Dieckmeyer Michael , Ruschke Stefan , Eggers Holger , Kooijman Hendrik , Rummeny Ernst J. , Bauer Jan S. , Karampinos Dimitrios C.
Published: February 2015

Background

The assessment of bone marrow composition has recently gained significant attention due to its association with bone loss pathophysiology and cancer therapy‐induced bone marrow damage. The purpose of our study was to investigate the anatomical variation of the vertebral bone marrow fat using chemical shift‐encoding based water‐fat MRI and to assess the repeatability of these measurements.

Methods

Chemical shift‐encoding based water‐fat MRI of the whole spine was performed in 28 young, healthy subjects (17 males, 11 females, 26 ± 4 years). Six subjects were scanned three times with repositioning to assess the repeatability of these measurements. Proton density fat fraction (PDFF) maps were computed and manually segmented to obtain PDFF of C3–L5.

Results

Mean PDFF of all subjects significantly increased from C3 to L5 (P < 0.05) with r = 0.88 (P < 0.05). PDFF averaged over C3–7, T1–6, T7–12, and L1–5 of males and females amounted to 31.7 ± 7.9% and 23.0 ± 7.8% (P = 0.002), 33.8 ± 6.8% and 24.6 ± 8.8% (P = 0.005), 33.8 ± 6.4% and 26.1 ± 6.4% (P = 0.023), and 38.8 ± 7.6% and 31.5 ± 12.4% (P = 0.063), respectively. The repeatability for PDFF measurements expressed as absolute precision error was 1.7% averaged over C3–L5.

Conclusion

Whole spine vertebral bone marrow fat could be reproducibly assessed by using chemical shift‐encoding based water‐fat MRI and showed anatomical variations. J. Magn. Reson. Imaging 2015;42:1018–1023.
Posttraumatic Stress Symptom Trajectories Among Children Exposed to Violence
Authors: Miller‐Graff Laura E. , Howell Kathryn H.
Published: February 2015

Little research has examined the developmental course of posttraumatic stress symptoms (PTSS) in children. The current study aimed to identify developmental trajectories of PTSS in childhood and to examine predictors of symptom presentation in 1,178 children from the Longitudinal Studies of Child Abuse and Neglect (LONGSCAN) studies, a consortium of studies focusing on the causes and effects of child maltreatment. Most children had a history of documented reports with Child Protective Services (CPS) and all were identified as living in high‐risk environments. Using group‐based trajectory modeling, 3 unique developmental trajectories were identified: Resilient, Clinical‐Improving (PTSS in the clinical range at baseline then declining over time), and Borderline‐Stable (chronically subclinical PTSS). Children in the Clinical‐Improving group were more likely than children in the Resilient group to have reports of physical abuse (RRR = 1.76), emotional abuse (RRR = 2.55), neglect (RRR = 1.57), and exposure to violence at home and in the community (RRR = 1.04). Children in the Borderline‐Stable group were more likely than children in the Resilient group to have a CPS history of neglect (RRR = 2.44) and exposure to violence at home and in the community (RRR = 1.04). Many children living in high‐risk environments exhibit resilience to PTSS, but exposure to witnessed violence and neglect appear to put children at chronic risk for poor adjustment. These children may require more intensive, integrated clinical services that attend to multiple adverse experiences.
Polymer – graphene nanocomposites: effect of polymer matrix and filler amount on properties
Authors: Mittal Vikas , Chaudhry Ali Usman
Published: February 2015

Nanocomposites of high density polyethylene (HDPE), linear low density polyethylene (LLDPE), polypropylene (PP), polystyrene (PS) and polycarbonate (PC) with thermally reduced graphene were generated by melt mixing. The HDPE nanocomposites had increment in the tensile (>50%) and storage modulus as a function of filler fraction. LLDPE had the highest enhancements of ≈100% in tensile modulus, 60% in break stress and 30% in tensile stress. PS exhibited least extent of property improvement, though the absolute modulus and strength were the highest for PS nanocomposites indicating the final properties of nanocomposites result from a combination of factors like polarity match between polymer and filler, processing conditions and physical properties of the polymer matrix.
The existence of light‐like homogeneous geodesics in homogeneous Lorentzian manifolds
Authors: Dušek Zdeněk
Published: February 2015

In previous papers, a fundamental affine method for studying homogeneous geodesics was developed. Using this method and elementary differential topology it was proved that any homogeneous affine manifold and in particular any homogeneous pseudo‐Riemannian manifold admits a homogeneous geodesic through arbitrary point. In the present paper this affine method is refined and adapted to the pseudo‐Riemannian case. Using this method and elementary topology it is proved that any homogeneous Lorentzian manifold of even dimension admits a light‐like homogeneous geodesic. The method is illustrated in detail with an example of the Lie group of dimension 3 with an invariant metric, which does not admit any light‐like homogeneous geodesic.
Current Concepts in the Treatment of Multiple System Atrophy
Authors: Perez‐Lloret Santiago , Flabeau Olivier , Fernagut Pierre‐Olivier , Pavy‐Le Traon Anne , Rey María Verónica , Foubert‐Samier Alexandra , Tison Francois , Rascol Olivier , Meissner Wassilios G.
Published: February 2015

MSA is a progressive neurodegenerative disorder characterized by autonomic failure and a variable combination of poor levodopa‐responsive parkinsonism and cerebellar ataxia (CA). Current therapeutic management is based on symptomatic treatment. Almost one third of MSA patients may benefit from l‐dopa for the symptomatic treatment of parkinsonism, whereas physiotherapy remains the best therapeutic option for CA. Only midodrine and droxidopa were found to be efficient for neurogenic hypotension in double‐blind, controlled studies, whereas other symptoms of autonomic failure may be managed with off‐label treatments. To date, no curative treatment is available for MSA. Recent results of neuroprotective and ‐restorative trials have provided some hope for future advances. Considerations for future clinical trials are also discussed in this review.
Photocurrent enhancement in thin‐film silicon solar cells by combination of anti‐reflective sub‐wavelength structures and light‐trapping textures
Authors: Sai Hitoshi , Matsui Takuya , Saito Kimihiko , Kondo Michio , Yoshida Isao
Published: February 2015

Dielectric films with anti‐reflective sub‐wavelength structures are applied to thin‐film silicon solar cells to improve the light incoupling at the front surface. It is verified that modification of the refractive index of the incident medium using dielectric films with sub‐wavelength structures is beneficial to reduce the average reflectivity of Si solar cells with an anti‐reflective coating based on optical interference. It is also shown that the sub‐wavelength structure must be combined with a proper light‐trapping texture to enhance the absorption within thin‐film silicon solar cells. The effectiveness of dielectric films with sub‐wavelength structures is demonstrated by an increase of the short‐circuit current density of a microcrystalline silicon cell from 29.1 to 30.4 mA/cm2 in a designated area of 1 cm2. The optical interplay between the dielectric films and the light‐trapping textures is also discussed. Copyright © 2015 John Wiley & Sons, Ltd.
Iodonium‐polyoxometalate and thianthrenium‐polyoxometalate as new one‐component UV photoinitiators for radical and cationic polymerization
Authors: Mokbel Haifaa , Xiao Pu , Simonnet‐Jégat Corine , Dumur Frederic , Gigmes Didier , Toufaily Joumana , Hamieh Tayssir , Fouassier Jean Pierre , Lalevée Jacques
Published: February 2015

Four novel onium salts (onium‐polyoxometalate) have been synthesized and characterized. They contain a diphenyliodonium or a thianthrenium (TH) moiety and a polyoxomolybdate or a polyoxotungstate as new counter anions. Outstandingly, these counter anions are photochemically active and can sensitize the decomposition of the iodonium or TH moiety through an intramolecular electron transfer. The phenyl radicals generated upon UV light irradiation (Xe–Hg lamp) are very efficient to initiate the radical polymerization of acrylates. Cations are also generated for the cationic polymerization of epoxides. Remarkably, these novel iodonium and TH salts are characterized by a higher reactivity compared with that of the diphenyliodonium hexafluorophosphate and the commercial TH salt, respectively. Interpenetrating polymer networks can also be obtained under air through a concomitant cationic/radical photopolymerization of an epoxy/acrylate blend (monomer conversions > 65%). The photochemical mechanisms are studied by steady‐state photolysis, cyclic voltammetry, and electron spin resonance techniques. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2015, 53, 981–989
Synthesis, characterization, and properties of vinyl‐terminated copolysiloxanes containing trifluoropropyl and 4‐trifluoromethylphenyl groups
Authors: Fei Hua‐Feng , Gao Xiyin , Han Xiaojie , Wang Qian , Hu Tao , Zhang Zhijie , Xie Zemin
Published: February 2015

Novel fluorine containing siloxane monomer, namely, 4‐trifluoromethylphenylmethyl cyclosiloxane (PF3) and mixed cyclosiloxane including both 4‐trifluoromethylphenylmethyl siloxane (P) unit and trifluoropropyl siloxane (F) unit were successfully synthesized in this study. Furthermore, their series including vinyl‐terminated copolymers with different compositions were synthesized. The microstructures of copolymers were investigated by1H NMR,29Si NMR,19F NMR, Fourier transform infrared spectroscopy, and differential scanning calorimetry (DSC). The results of characterizations confirmed that the copolymers exhibited random microstructure. Moreover, the analysis of the result of DSC also revealed that the copolymers had a low glass transition temperature. The thermogravimetric analysis indicated that poly(4‐trifluoromethylphenylmethyl)siloxane (PPF3) exhibited higher thermal stability than conventional fluorosilicones rubber (FSR). The dynamic mechanical analysis showed that the damping factors of these copolymers were greater than 0.3 in a wide range of temperature. The mass swelling ratios were less than 5.5% when the samples were immersed in No. 3 jet fuel for a month. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem.2015,53, 1023–1031
Thermodynamic binding analysis of Notch transcription complexes from Drosophila melanogaster
Authors: Contreras Ashley N. , Yuan Zhenyu , Kovall Rhett A.
Published: February 2015

Notch is an intercellular signaling pathway that is highly conserved in metazoans and is essential for proper cellular specification during development and in the adult organism. Misregulated Notch signaling underlies or contributes to the pathogenesis of many human diseases, most notably cancer. Signaling through the Notch pathway ultimately results in changes in gene expression, which is regulated by the transcription factor CSL. Upon pathway activation, CSL forms a ternary complex with the intracellular domain of the Notch receptor (NICD) and the transcriptional coactivator Mastermind (MAM) that activates transcription from Notch target genes. While detailed in vitro studies have been conducted with mammalian and worm orthologous proteins, less is known regarding the molecular details of the Notch ternary complex in Drosophila. Here we thermodynamically characterize the assembly of the fly ternary complex using isothermal titration calorimetry. Our data reveal striking differences in the way the RAM (RBP‐J associated molecule) and ANK (ankyrin) domains of NICD interact with CSL that is specific to the fly. Additional analysis using cross‐species experiments suggest that these differences are primarily due to fly CSL, while experiments using point mutants show that the interface between fly CSL and ANK is likely similar to the mammalian and worm interface. Finally, we show that the binding of the fly RAM domain to CSL does not affect interactions of the corepressor Hairless with CSL. Taken together, our data suggest species‐specific differences in ternary complex assembly that may be significant in understanding how CSL regulates transcription in different organisms.
Density of α4β2* nAChR on the surface of neurons is modulated by chronic antagonist exposure
Authors: Zambrano Cristian A. , Short Caitlin A. , Salamander Rakel M. , Grady Sharon R. , Marks Michael J.
Published: February 2015

The expression of high‐affinity α4β2* nicotinic acetylcholine receptors (nAChR) increases following chronic exposure to nicotinic agonists. While, nAChR antagonists can also produce upregulation, these changes are often less pronounced than achieved with agonists. It is unknown if nAChR agonists and antagonists induce receptor upregulation by the same mechanisms. In this study, primary neuronal cultures prepared from cerebral cortex, hippocampus, diencephalon, and midbrain/hindbrain of C57BL/6J mouse embryos were treated chronically with nicotine (agonist), mecamylamine (noncompetitive antagonist) or dihydro‐β‐erythroidine (competitive antagonist) or the combination of nicotine with each antagonist. The distribution of intracellular and surface [125I]epibatidine‐binding sites were subsequently measured. Treatment with 1 μmol/L nicotine upregulated intracellular and cell surface [125I]epibatidine binding after 96 h. Chronic dihydro‐β‐erythroidine (10 μmol/L) treatment also increased [125I]epibatidine binding on the cell surface; however, mecamylamine was ineffective in upregulating receptors by itself. The combination of 1 μmol/L nicotine plus 10 μmol/L mecamylamine elicited a significantly higher upregulation than that achieved by treatment with nicotine alone due to an increase of [125I]epibatidine binding on the cell surface. This synergistic effect of mecamylamine and nicotine was found in neuronal cultures from all four brain regions. Chronic treatment with nicotine concentrations as low as 10 nmol/L produced upregulation of [125I]epibatidine binding. However, the effect of mecamylamine was observed only after coincubation with nicotine concentrations equal to or greater than 100 nmol/L. Vesicular trafficking was required for both nicotine and nicotine plus mecamylamine‐induced upregulation. Results presented here support the idea of multiple mechanisms for nAChR upregulation.
A single‐dose mass balance and metabolite‐profiling study of vemurafenib in patients with metastatic melanoma
Authors: Goldinger Simone M. , Rinderknecht Jeannine , Dummer Reinhard , Kuhn Felix Pierre , Yang Kuo‐Hsiung , Lee Lucy , Ayala Ruben C. , Racha Jagdish , Geng Wanping , Moore David , Liu Mei , Joe Andrew K. , Bazan Selby Patricia Gil , Grippo Joseph F.
Published: February 2015

Vemurafenib, a selective inhibitor of oncogenic BRAF kinase carrying the V600 mutation, is approved for treatment of advanced BRAF mutation–positive melanoma. This study characterized mass balance, metabolism, rates/routes of elimination, and disposition of 14C‐labeled vemurafenib in patients with metastatic melanoma. Seven patients with metastatic BRAF‐mutated melanoma received unlabeled vemurafenib 960 mg twice daily for 14 days. On the morning of day 15, patients received 14C‐labeled vemurafenib 960 mg (maximum 2.56 MBq [69.2 μCi]). Thereafter, patients resumed unlabeled vemurafenib (960 mg twice daily). Blood, urine, and feces were collected for metabolism, pharmacokinetic, and dose recovery analysis. Within 18 days after dose, ~95% of 14C‐vemurafenib–related material was recovered from feces (94.1%) and urine (<1%). The parent compound was the predominant component (95%) in plasma. The mean plasma elimination half‐life of 14C‐vemurafenib–related material was 71.1 h. Each metabolite accounted for <0.5% and ≤6% of the total administered dose in urine and feces, respectively (0–96 h postdose). No new metabolites were detected. Vemurafenib was well‐tolerated. Excretion of vemurafenib via bile into feces is considered the predominant elimination route from plasma with minor renal elimination (<1%).
Structural characterization of triple transmembrane domain containing fragments of a yeast G protein‐coupled receptor in an organic : aqueous environment by solution‐state NMR spectroscopy
Authors: Fracchiolla Katrina E. , Cohen Leah S. , Arshava Boris , Poms Martin , Zerbe Oliver , Becker Jeffrey M. , Naider Fred
Published: February 2015

This report summarizes recent biophysical and protein expression experiments on polypeptides containing the N‐terminus, the first, second, and third transmembrane (TM) domains and the contiguous loops of the α‐factor receptor Ste2p, a G protein‐coupled receptor. The 131‐residue polypeptide Ste2p(G31‐R161), TM1–TM3, was investigated by solution NMR in trifluoroethanol/water. TM1–TM3 contains helical TM domains at the predicted locations, supported by continuous sets of medium‐range NOEs. In addition, a short helix N‐terminal to TM1 was detected, as well as a short helical stretch in the first extracellular loop. Two 161‐residue polypeptides, [Ste2p(M1‐R161), NT–TM1–TM3], that contain the entire N‐terminal sequence, one with a single mutation, were directly expressed and isolated from Escherichia coli in yields as high as 30 mg/L. Based on its increased stability, the L11P mutant will be used in future experiments to determine long‐range interactions. The study demonstrated that 3‐TM domains of a yeast G protein‐coupled receptor can be produced in isotopically labeled form suitable for solution NMR studies. The quality of spectra is superior to data recorded in micelles and allows more rapid data analysis. No tertiary contacts have been determined, and if present, they are likely transient. This observation supports earlier studies by us that secondary structure was retained in smaller fragments, both in organic solvents and in detergent micelles, but that stable tertiary contacts may only be present when the protein is imbedded in lipids. Copyright © 2015 European Peptide Society and John Wiley & Sons, Ltd.
Role of the changing sign of effective electron–electron correlation energy for information recording in PCM
Authors: Bogoslovskiy Nikita , Tsendin Konstantin
Published: February 2015

We consider the centers with negative electron–electron correlation energy. It is shown that in strong electric field the effective electron–electron correlation energy can become positive. As a result the Fermi level shifts and the conductivity increases sharply which we call the conductivity transition. This transition may cause the nonlinearity and a sufficient increase of the current density while data recording in chalcogenide‐based phase‐change memory (PCM).
Room‐temperature growth of ion‐induced Si‐ and Ge‐incorporated carbon nanofibers
Authors: Yaakob Yazid , Kuwataka Yu , Yusop Mohd Zamri Mohd , Tanaka Shihomi , Rosmi Mohamad Saufi , Kalita Golap , Tanemura Masaki
Published: February 2015

We have demonstrated the fabrication of Si‐ and Ge‐incorporated carbon nanofibers (CNFs) at room temperature. Graphite foil surfaces were irradiated by Ar+ and Ne+ ions with simultaneous Si and Ge supply, and the dependences of the ion‐induced composite CNFs surface morphology on the ion species and type of incorporated materials were investigated. The sample surfaces were characterized by various kinds of densely distributed nanostructures, such as conical protrusions, nanoneedles, nanocones, and CNF‐tipped cones, depending on the Si and Ge supply rates during ion irradiation. In addition, Ne+ irradiation yielded longer CNFs compared to Ar+‐irradiated CNFs. Thus, the nanostructures growth was controllable by adjusting the ion and material species.

Surface morphology of ion‐induced Ge‐incorporated CNFs.
Income Inequality and the Online Reading Gap
Authors: Leu Donald J. , Forzani Elena , Kennedy Clint
Published: February 2015

A recent study in Reading Research Quarterly provided evidence that an online reading achievement gap, based on income inequality, exists that is separate and independent from the well‐known achievement gap in offline reading. This column briefly reviews the evidence and provides an initial set of instructional suggestions that may be used to help close the gap.
First two unrelated cases of isolated sedoheptulokinase deficiency: A benign disorder?
Authors: Wamelink Mirjam M. C. , Ramos Ruben J. J. F. , den van Elzen Annette P. M. , Ruijter George J. G. , Bonte Ramon , Diogo Luisa , Garcia Paula , Neves Nelson , Nota Benjamin , Haschemi Arvand , Tavares de Almeida Isabel , Salomons Gajja S.
Published: February 2015

We present the first two reported unrelated patients with an isolated sedoheptulokinase (SHPK) deficiency. The first patient presented with neonatal cholestasis, hypoglycemia, and anemia, while the second patient presented with congenital arthrogryposis multiplex, multiple contractures, and dysmorphisms. Both patients had elevated excretion of erythritol and sedoheptulose, and each had a homozygous nonsense mutation in SHPK. SHPK is an enzyme that phosphorylates sedoheptulose to sedoheptulose‐7‐phosphate, which is an important intermediate of the pentose phosphate pathway. It is questionable whether SHPK deficiency is a causal factor for the clinical phenotypes of our patients. This study illustrates the necessity of extensive functional and clinical workup for interpreting a novel variant, including nonsense variants.
Perceptions of Tissue Storage in a Dementia Population Among Spouses and Offspring
Authors: Martin Megan M. , Rothwell Erin W. , Venne Vickie L. , Foster Norman L.
Published: February 2015

Cognitively impaired patients with dementia often rely on health advocates or guardians, such as spouses or adult offspring, to consent for medical procedures. These family members may also decide whether an autopsy is performed after death or whether their family member donates tissues. However, spouses are not genetically related to the patient and may have different perspectives than genetically related family members when making medical decisions with genetic implications, such as participation in a tissue repository (biobank). Interviews were conducted with spouses and adult offspring of individuals with a progressive dementing disease. Both spouses and offspring were supportive of the patient with dementia to participate in tissue storage. The top perceived benefits of tissue storage in both offspring and spouses were future value for family members and advancement of medical knowledge. Concerns included misuse of the tissue and insurance discrimination. Although the personal genetic implications differ between spouses and offspring, they share similar attitudes about the importance of tissue banking for the individual with a dementing disease.
Numerical simulations of aggregate breakup in bounded and unbounded turbulent flows
Authors: Babler Matthaus U. , Biferale Luca , Brandt Luca , Feudel Ulrike , Guseva Ksenia , Lanotte Alessandra S. , Marchioli Cristian , Picano Francesco , Sardina Gaetano , Soldati Alfredo , Toschi Federico
Published: February 2015

Breakup of small aggregates in fully developed turbulence is studied by means of direct numerical simulations in a series of typical bounded and unbounded flow configurations, such as a turbulent channel flow, a developing boundary layer and homogeneous isotropic turbulence. The simplest criterion for breakup is adopted, whereby aggregate breakup occurs when the local hydrodynamic stress ${\it\sigma}\sim {\it\varepsilon}^{1/2}$, with ${\it\varepsilon}$ being the energy dissipation at the position of the aggregate, overcomes a given threshold ${\it\sigma}_{cr}$, which is characteristic for a given type of aggregate. Results show that the breakup rate decreases with increasing threshold. For small thresholds, it develops a scaling behaviour among the different flows. For high thresholds, the breakup rates show strong differences between the different flow configurations, highlighting the importance of non-universal mean-flow properties. To further assess the effects of flow inhomogeneity and turbulent fluctuations, the results are compared with those obtained in a smooth stochastic flow. Furthermore, we discuss the limitations and applicability of a set of independent proxies.
Depth-integrated equation for hydro-acoustic waves with bottom damping
Authors: Abdolali Ali , Kirby James T. , Bellotti Giorgio
Published: February 2015

We present a depth-integrated equation for the mechanics of generation, propagation and dissipation of low-frequency hydro-acoustic waves due to sudden bottom displacement in a weakly compressible ocean overlying a weakly compressible viscous sediment layer. The model is validated against a full 3D computational model. Physical properties of these waves are studied and compared with those for waves over a rigid sea bed, revealing changes in the frequency spectrum and modal peaks. The resulting model equation can be used for numerical prediction in large-scale domains, overcoming the computational difficulties of 3D models while taking into account the role of bottom dissipation on hydro-acoustic wave generation and propagation.
Second language speech production: Investigating linguistic correlates of comprehensibility and accentedness for learners at different ability levels
Authors: SAITO KAZUYA , TROFIMOVICH PAVEL , ISAACS TALIA
Published: February 2015

The current project aimed to investigate the potentially different linguistic correlates of comprehensibility (i.e., ease of understanding) and accentedness (i.e., linguistic nativelikeness) in adult second language (L2) learners’ extemporaneous speech production. Timed picture descriptions from 120 beginner, intermediate, and advanced Japanese learners of English were analyzed using native speaker global judgments based on learners’ comprehensibility and accentedness, and then submitted to segmental, prosodic, temporal, lexical, and grammatical analyses. Results showed that comprehensibility was related to all linguistic domains, and accentedness was strongly tied with pronunciation (specifically segmentals) rather than lexical and grammatical domains. In particular, linguistic correlates of L2 comprehensibility and accentedness were found to vary by learners’ proficiency levels. In terms of comprehensibility, optimal rate of speech, appropriate and rich vocabulary use, and adequate and varied prosody were important for beginner to intermediate levels, whereas segmental accuracy, good prosody, and correct grammar featured strongly for intermediate to advanced levels. For accentedness, grammatical complexity was a feature of intermediate to high-level performance, whereas segmental and prosodic variables were essential to accentedness across all levels. These findings suggest that syllabi tailored to learners’ proficiency level (beginner, intermediate, or advanced) and learning goal (comprehensibility or nativelike accent) would be advantageous for the teaching of L2 speaking.
Larger chimpanzee-dispersed seeds are elongated at Mahale, Tanzania: possible consequence of plant–disperser interaction?
Authors: Nakamura Michio , Itoh Noriko
Published: February 2015

Apes are important long-distance dispersers of large seeds in African tropical forests. Seed size and shape are likely to affect the ease of swallowing for an animal species. If an endozoochorous seed is larger than the digestive tract of an animal, the seed cannot be swallowed, and a round seed is more difficult to swallow than an elongated seed of the same length. In order to test if such a correlation exists between the seed size and its shape, we investigated the length and width of chimpanzee-dispersed seeds at the Mahale Mountains National Park, Tanzania. Among the 14 species of seeds, longer seeds had significantly narrower relative widths, and thus, they were more ovoid. Since the chimpanzee is the largest arboreal frugivore at Mahale, their food selection might have influenced the shape of larger seeds. The chimpanzee's selective consumption of such fruits with longer, elongated seeds may have facilitated the selective dispersal of such plant species in that area.