bluuebunny/crossref_metadata_2025 huggingface dataset:
Chiral Inhibition of Rivaroxaban Derivatives Towards UDP‐Glucuronosyltransferase (UGT) Isoforms
Authors: Yao Zhuhua , Liu Yong‐Zhe , Ma Ai‐Lun , Wang Shu‐Fen , Lu Dan , Hu Cui‐Min , Zhang Yan‐Yan , Wang Haina , Hu Lingyun , Deng Jun , Yang Kun , Fang Zhong‐Ze
Published: October 2015

Rivaroxaban is an oral direct factor Xa (FXa) inhibitor clinically used to prevent and treat thromboembolic disorders. Drug–drug interaction (DDI) exist for rivaroxaban and the inhibitors of CYP3A4/5. This study aims to investigate the inhibition of rivaroxaban and its derivatives with a chiral center towards UDP‐glucuronosyltransferases (UGTs). Chemical synthesis was performed to obtain rivaroxaban derivatives with different chiral centers. UGTs supersomes‐catalyzed 4‐methylumbelliferone (4‐MU) glucuronidation was employed to evaluate the inhibition potential towards various UGT isoforms. A significant influence of rivaroxaban derivatives towards UGT1A3 was observed. Chiral centers produce different effects towards the effect of four pairs of rivaroxaban derivatives towards UGT1A3 activity, with stronger inhibition potential of S1 than R1, but stronger inhibition capability of R2, R3, R4 than S2, S3, and S4. Competitive inhibition of R3 and R4 towards UGT1A3 was demonstrated by Dixon and Lineweaver‐Burk plots. In conclusion, the significant influence of rivaroxaban derivatives towards UGT1A3's activity was demonstrated in the present study. The chirality centers highly affected the inhibition behavior of rivaroxaban derivatives towards UGT1A3. Chirality 27:936–943, 2015. © 2015 Wiley Periodicals, Inc.
Concepts and Molecular Aspects in the Polypharmacology of PARP‐1 Inhibitors
Authors: Passeri Daniela , Camaioni Emidio , Liscio Paride , Sabbatini Paola , Ferri Martina , Carotti Andrea , Giacchè Nicola , Pellicciari Roberto , Gioiello Antimo , Macchiarulo Antonio
Published: October 2015

Recent years have witnessed a renewed interest in PARP‐1 inhibitors as promising anticancer agents with multifaceted functions. Particularly exciting developments include the approval of olaparib (Lynparza) for the treatment of refractory ovarian cancer in patients with BRCA1/2 mutations, and the increasing understanding of the polypharmacology of PARP‐1 inhibitors. The aim of this review article is to provide the reader with a comprehensive overview of the distinct levels of the polypharmacology of PARP‐1 inhibitors, including 1) inter‐family polypharmacology, 2) intra‐family polypharmacology, and 3) multi‐signaling polypharmacology. Progress made in gaining insight into the molecular basis of these multiple target‐independent and target‐dependent activities of PARP‐1 inhibitors are discussed, with an outlook on the potential impact that a better understanding of polypharmacology may have in aiding the explanation as to why some drug candidates work better than others in clinical settings, albeit acting on the same target with similar inhibitory potency.
Universality of Chaos and Ultrametricity in Mixed p‐Spin Models
Authors: Auffinger Antonio , Chen Wei‐Kuo
Published: October 2015

We prove disorder universality of chaos phenomena and ultrametricity in the mixed p‐spin model under mild moment assumptions on the environment. This establishes the longstanding belief among physicists that the solution of mean‐field models with Gaussian disorder also holds for different environments. Our results extend to the mixed p‐spin model as well as to different spin glass models. These include universality of quenched disorder chaos in the Edwards‐Anderson (EA) model and quenched concentration for the magnetization in both EA and mixed p‐spin models under non‐Gaussian environments. In addition, we show quenched self‐averaging for the overlap in the random field Ising model under small perturbation of the external field.© 2015 Wiley Periodicals, Inc.
Increasing Awareness of Potentially Helpful Motivations and Techniques for Forgiveness
Authors: Jeter Whitney K. , Brannon Laura A.
Published: October 2015

The authors examined 3 motives and 3 techniques for forgiveness to assess differences between people high or low in dispositional forgiveness (HDF and LDF, respectively). HDF participants rated all motives as more compelling and familiar than did LDF participants. Forgiveness being the right thing to do was rated as more persuasive and familiar; however, mental and physical health benefits were rated as compelling but less familiar forgiveness motives. LDF participants rated the various techniques as less familiar and more difficult compared with HDF participants. Overall, participants rated forgive and forget as the most familiar but most difficult technique to implement.
Center, Light, and Sound: The Psychological Benefits of Three Distinct Meditative Practices
Authors: Gutierrez Daniel , Fox Jesse , Wood Andrew W.
Published: October 2015

Meditation has been a popular topic in counseling and psychological research in recent years. However, other meditative practices have been gaining exposure recently of which counselors may not be aware. The current article provides a brief overview of 3 meditative practices: centering prayer, jyoti meditation, and acem meditation. The purpose of this article is to provide counselors with introductions to alternative meditative practices that may be otherwise overshadowed.
Organometallic Reactivity of [Silver(I)­(Pyridine‐Containing Ligand)] Complexes Relevant to Catalysis
Authors: Pedrazzini Tommaso , Pirovano Paolo , Dell'Acqua Monica , Ragaini Fabio , Illiano Pasquale , Macchi Piero , Abbiati Giorgio , Caselli Alessandro
Published: October 2015

Silver(I) complexes of pyiridine‐containing macrocyclic ligands (Pc‐L) have already been demonstrated as active catalysts for some domino and multicomponent reactions. Here, we report new chiral [AgI(Pc‐L*)] cationic complexes that have been synthesized and fully characterized, including structural determination by single‐crystal X‐ray diffraction. The complexes show a rich coordination chemistry, demonstrating both the σ‐philic (alcohol and nitrile coordination) and the π‐philic (alkyne coordination) nature of silver. The η2 coordination mode of the naphthyl pendant arm of the ligands on silver has been observed in solution by NMR spectroscopic experiments. 2D NMR spectroscopy revealed the presence of positive cross peaks resulting from rotational processes and the rate of rotation was measured by using 2D exchange spectroscopy (EXSY).
Iodinated Bis(phthalocyaninato)terbium(III) Complexes: Versatile Platforms for Functionalization of Single‐Molecule Magnets through Sonogashira Reaction
Authors: Bertani Federico , Cristiani Nicola , Mannini Matteo , Pinalli Roberta , Sessoli Roberta , Dalcanale Enrico
Published: October 2015

Novel homoleptic octaiodinated bis(phthalocyaninato)terbium(III) complex Tb(PcI4)2 (1) and its heteroleptic counterpart tetraiodinated TbPc(PcI4) have been synthesized in their neutral forms and fully characterized. Their magnetic properties have been evaluated by standard magnetometry, and the results confirm the single‐molecule magnet behavior of these two complexes. The eight aryl iodine moieties in the homoleptic derivative 1 have been exploited to test the Sonogashira reaction with 4‐pentyn‐1‐ol as alkynyl substrate at room temperature under standard conditions. The application of this new synthetic protocol for TbPc2 functionalization to different substrates will allow the introduction of a wide range of functionalities on LnPc2, which is a necessary prerequisite for the development of SMM‐based technologies.
The Intestinal Microbiome in Bariatric Surgery Patients
Authors: Peat Christine M. , Kleiman Susan C. , Bulik Cynthia M. , Carroll Ian M.
Published: October 2015

With nearly 39% of the worldwide adult population classified as obese, much of the globe is facing a serious public health challenge. Increasing rates of obesity, coupled with the failure of many behavioural and pharmacological interventions, have contributed to a rise in popularity of bariatric surgery as a treatment for obesity. Surgery‐mediated weight loss was initially thought to be a direct result of mechanical alterations causing restriction and calorie malabsorption. However, the mounting evidence suggests that indirect factors influence the accumulation and storage of fat in patients that have undergone this procedure. Given the established impact the intestinal microbiota has on adiposity, it is likely that this complex enteric microbial community contributes to surgery‐mediated weight loss and maintenance of weight loss postsurgery. In this review, we discuss the physiological and psychological traits exhibited by bariatric surgery candidates that can be influenced by the intestinal microbiota. Additionally, we detail the studies that investigated the impact of bariatric surgery on the intestinal microbiota in humans and mouse models of this procedure. Copyright © 2015 John Wiley & Sons, Ltd and Eating Disorders Association.
Morphodynamic evolution of a lower Mississippi River channel bar after sand mining
Authors: Yuill Brendan T. , Gaweesh Ahmed , Allison Mead A. , Meselhe Ehab A.
Published: October 2015

In‐channel sand mining by dredge removes large quantities of bed sediment and alters channel morphodynamic processes. While the reach‐scale impacts of dredging are well documented, the effects of the dredged borrow pit on the local flow and sediment transport are poorly understood. These local effects are important because they control the post‐dredge evolution of the borrow pit, setting the pit lifespan and affecting reach‐scale channel morphology. This study documents the observed morphological evolution of a large (1·46 million m3) borrow pit mined on a lateral sandbar in the lower Mississippi River using a time‐series of multibeam bathymetric surveys. During the 2·5 year time‐series, 53% of the initial pit volume infilled with sediment, decreasing pit depth by an average of 0·88 m yr−1. To explore the controls of the observed infilling, a morphodynamic model (Delft3D) was used to simulate flow and sediment transport within the affected river reach. The model indicated that infilling rates were primarily related to the riverine sediment supply and pit geometry. The pit depth and length influenced the predicted magnitude of the pit bed shear stress relative to its pre‐dredged value, i.e. the bed‐stress reduction ratio (R*), a metric that was correlated with the magnitude and spatial distribution of infilling. A one‐dimensional reduced‐complexity model was derived using predicted sediment supply and R* to simulate patterns of pit infilling. This simplified model of borrow‐pit evolution was able to closely approximate the amount and patterns of sediment deposition during the study period. Additional model experiments indicate that, for a borrow pit of a set volume, creating deep, longitudinally‐shorter borrow pits significantly increased infilling rates relative to elongated pits. Study results provide insight into the resilience of alluvial river channels after a disturbance and the sustainability of sand mining as a sediment source for coastal restoration. Copyright © 2015 John Wiley & Sons, Ltd.
The influence of melamine impregnation and heat treatment on the fire performance of Scots pine (Pinus sylvetris) wood
Authors: Lahtela Ville , Kärki Timo
Published: October 2015

Wood, as a natural and renewable resource, is a popular material for construction, but its fire performance restricts its utilization. In addition, for example, the mechanical properties of wood have up till now been impaired by the most common fire retardants, and therefore, the investigation of wood modification with not‐weakening flame retardants is essential. This study investigates the effects of melamine impregnation and heat treatment on the fire performance of Scots pine (Pinus sylvetris L.). The treated samples were tested with a cone calorimeter, and the following features were studied: time to ignition, heat release, smoke production, and mass loss. The heat‐treated samples became more homogenous as regards the results of fire performance. Some of the examined fire behavior values decreased because of heat treatment, while the same values increased after the combination of melamine impregnation and heat treatment. The smoke production was reduced the most for the samples that were both impregnated and heat treated. Although the influence of treatment on the fire behavior properties of solid wood was relatively marginal, it was assumed that these treatments will not have a negative impact on the fire‐resistance properties of pine wood. Copyright © 2015 John Wiley & Sons, Ltd.
A Time‐Simultaneous Prediction Box for a Multivariate Time Series
Authors: Kolsrud Dag
Published: October 2015

A sample‐based method in Kolsrud (Journal of Forecasting2007;26(3): 171–188) for the construction of a time‐simultaneous prediction band for a univariate time series is extended to produce a variable‐ and time‐simultaneous prediction box for a multivariate time series. A measure of distance based on theL∞‐norm is applied to a learning sample of multivariate time trajectories, which can be mean‐ and/or variance‐nonstationary. Based on the ranking of distances to the centre of the sample, a subsample of the most central multivariate trajectories is selected. A prediction box is constructed by circumscribing the subsample with a hyperrectangle. The fraction of central trajectories selected into the subsample can be calibrated by bootstrap such that the expected coverage of the box equals a prescribed nominal level. The method is related to the concept of data depth, and thence modified to increase coverage. Applications to simulated and empirical data illustrate the method, which is also compared to several other methods in the literature adapted to the multivariate setting. Copyright © 2015 John Wiley & Sons, Ltd.
Rapid methods for extracting and quantifying phenolic compounds in citrus rinds
Authors: Magwaza Lembe Samukelo , Opara Umezuruike Linus , Cronje Paul J. R. , Landahl Sandra , Ortiz Jose Ordaz , Terry Leon A.
Published: October 2015

Conventional methods for extracting and quantifying phenolic compounds in citrus rinds are time consuming. Rapid methods for extracting and quantifying phenolic compounds were developed by comparing three extraction solvent combinations (80:20 v/v ethanol:H2O; 70:29.5:0.5 v/v/v methanol:H2O:HCl; and 50:50 v/v dimethyl sulfoxide (DMSO):methanol) for effectiveness. Freeze‐dried, rind powder was extracted in an ultrasonic water bath at 35°C for 10, 20, and 30 min. Phenolic compound quantification was done with a high‐performance liquid chromatography (HPLC) equipped with diode array detector. Extracting with methanol:H2O:HCl for 30 min resulted in the optimum yield of targeted phenolic acids. Seven phenolic acids and three flavanone glycosides (FGs) were quantified. The dominant phenolic compound was hesperidin, with concentrations ranging from 7500 to 32,000 μg/g DW. The highest yield of FGs was observed in samples extracted, using DMSO:methanol for 10 min. Compared to other extraction methods, methanol:H2O:HCl was efficient in optimum extraction of phenolic acids. The limit of detection and quantification for all analytes were small, ranging from 1.35 to 5.02 and 4.51 to 16.72 μg/g DW, respectively, demonstrating HPLC quantification method sensitivity. The extraction and quantification methods developed in this study are faster and more efficient. Where speed and effectiveness are required, these methods are recommended.
Association between nucleos(t)ide analog and tumor recurrence in hepatitis B virus–related hepatocellular carcinoma after radiofrequency ablation
Authors: Lee Teng‐Yu , Lin Jaw‐Town , Zeng Yi‐Siou , Chen Yi‐Ju , Wu Ming‐Shiang , Wu Chun‐Ying
Published: October 2015

Radiofrequency ablation (RFA) is the best choice for curative treatment of hepatocellular carcinoma (HCC) cases not suitable for surgical intervention, but efforts should be made to reduce the risk of tumor recurrence. We aimed to investigate the association between nucleos(t)ide analog (NA) therapy for hepatitis B virus (HBV) and the risk of HCC recurrence post‐RFA. Using the Taiwan National Health Insurance Research Database between July 1, 2004 and December 31, 2012, we screened 48,807 patients with newly diagnosed HBV‐related HCC. We identified 850 patients (200 patients who used NAs for more than 90 days and 650 who never used NA post‐RFA) who received RFA as a potentially curative treatment for HCC. Patients in the NA‐treated cohort were randomly matched 1:2 with patients in the untreated cohort by age, sex, cirrhosis, and the time period between RFA and initiation of NA therapy. Finally, 133 patients were recruited in the NA‐treated group and 266 in the untreated group for analysis. Cumulative incidences of and hazard ratios (HRs) for HCC recurrence were analyzed after adjusting for competing mortality. The HCC recurrence rate of the NA‐treated group was significantly lower than that of the untreated group (2‐year recurrence rate: 41.8%; 95% confidence interval [CI]: 32.9‐50.6 vs. 54.3%; 95% CI: 48.0‐60.6; modified log‐rank test: P < 0.05). In modified Cox's regression analysis, NA therapy was independently associated with a decreased risk of HCC recurrence (HR, 0.69; 95% CI: 0.50‐0.95; P < 0.05). Multivariate stratified analyses verified the association of NA therapy and decreased HCC recurrence in almost all patient subgroups. Conclusion: NA therapy was associated with a decreased risk of HCC recurrence among patients with HBV‐related HCC post‐RFA. (Hepatology 2016;63:1517‐1527)
Biocompatibility and biomechanical analysis of elastic TPU threads as new suture material
Authors: Vogels Ruben R. M. , Lambertz Andreas , Schuster Philipp , Jockenhoevel Stefan , Bouvy Nicole D. , Disselhorst‐Klug Catherine , Neumann Ulf P. , Klinge Uwe , Klink Christian D.
Published: October 2015

High suture tension is one of the causes for many wound‐healing problems. Constriction of tissue within the suture loops of nonelastic sutures can lead to cutting of the suture through tissues and necrosis of the tissue within these loops. The use of elastic materials in new suture types could give the material the ability to adapt tension to the tissue requirements and subsequently lead to more vital tissue within its loops. We evaluated the foreign body host response, as indicator of biocompatibility, to a new thermoplastic poly(carbonate) urethane (TPU) synthetic suture material in a rat model compared with standard nonelastic polypropylene (PP) sutures. Tissue samples were collected at 7 and 21 days, and host response was evaluated. Subsequently, suture tension curves of the new elastic sutures for the first 30 min after knotting were recorded in a pig model. The new TPU sutures showed an improved foreign body response when compared with that of PP, with a reduction in the amount of macrophages surrounding the material. Tension experiments showed a superior tension curve for TPU sutures, with a major reduction in peak suture tension when compared with that of standard PP sutures, while still retaining adequate tension after 30 min. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 99–106, 2017.
Bioactive glass plus laser phototherapy as promise candidates for dentine hypersensitivity treatment
Authors: Lopez Talita Christine Camilo , Diniz Ivana Márcia Alves , Ferreira Leila Soares , Marchi Juliana , Borges Roger , de Cara Sueli Patricia Harumi Miyagi , D'Almeida‐Couto Roberta , Marques Márcia Martins
Published: October 2015

Treatments for dentine hypersensitivity (DH) may produce positive effects, though do not have lasting results. We investigated the reparative potential of stem cells derived from deciduous teeth (SHEDs) in response to components delivered from substances used in the treatment of the DH, associated or not to laser phototherapy (LPT), to stimulate dentine formation. SHEDs were submitted to substances delivered from a laboratorial P‐rich bioactive glass [57SiO2−26CaO‐17P2O5 (wt %)] or a commercially available desensitizer (Gluma® Desensitizer), associated (or not) to LPT (InGAlP diode laser, 660 nm, 0.028 cm2, 20 mW, 5 J/cm2, 7 s, contact mode). Biomaterial characterization was performed by X‐ray diffraction, scanning electron microscopy and the particle size was evaluated by dynamic light scattering. SHEDs proliferation and differentiation were analyzed by MTT and Alizarin Red staining, respectively. The conditioned media used in these tests were evaluated regarding their pH and the ionic concentration changes due to ions leached from the bioactive glass (BG). BG majority presented a non‐crystalline solid structure and mixed particle sizes characterized by the agglomeration of nanoparticles. Cultures treated with BG alone or in association to LPT showed improved cell growth in relation to Gluma® (p < 0.05). Gluma® was cytotoxic in all tested conditions, regardless irradiated or not. BG associated to LPT induced intense mineral matrix formation. In conclusion, BG releases ionic dissolution products able to promote SHEDs differentiation. BG associated to LPT improves SHEDs proliferation and differentiation in vitro, and may be a promise therapeutic approach for the DH treatment. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 107–116, 2017.
Control of hydroxyapatite coating by self‐assembled monolayers on titanium and improvement of osteoblast adhesion
Authors: Shen Juan , Qi Yongcheng , Jin Bo , Wang Xiaoyan , Hu Yamin , Jiang Qiying
Published: October 2015

Self‐assembly technique was applied to introduce functional groups and form hydroxyl‐, amine‐, and carboxyl‐terminal self‐assembled monolayers (SAMs). The SAMs were grafted onto titanium substrates to obtain a molecularly smooth functional surface. Subsequent hydrothermal crystal growth formed homogeneous and crack‐free crystalline hydroxyapatite (HA) coatings on these substrates. AFM and XPS were used to characterize the SAM surfaces, and XRD, SEM, and TEM were used to characterize the HA coatings. Results show that highly crystalline, dense, and oriented HA coatings can be formed on the OH–, NH2–, and COOH–SAM surfaces. The SAM surface with –COOH exhibited stronger nucleating ability than that with –OH and –NH2. The nucleation and growth processes of HA coatings were effectively controlled by varying reaction time, pH, and temperature. By using this method, highly crystalline, dense, and adherent HA coatings were obtained. In addition, in vitro cell evaluation demonstrated that HA coatings improved cell adhesion as compared with pristine titanium substrate. The proposed method is considerably effective in introducing the HA coatings on titanium surfaces for various biomedical applications and further usage in other industries. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 124–135, 2017.
Smooth Muscle Cell Differentiation: Model Systems, Regulatory Mechanisms, and Vascular Diseases
Authors: Shi Ning , Chen Shi‐You
Published: October 2015

Smooth muscle cell (SMC) differentiation is an important process during vascular development. The highly differentiated mature SMCs play critical roles in maintaining structural and functional integrity of blood vessels. However, SMCs are not terminally differentiated, and their phenotype can be modulated between contractile and proliferative states in response to various environmental conditions. Alterations in SMC phenotype contribute to a number of major cardiovascular diseases such as atherosclerosis, hypertension and restenosis following angioplasty, etc. The goal of this review is to provide a brief overview of the recent advancements in our understanding of SMC differentiation and the development of in vitro SMC differentiation models, with a particular emphasis on examination of molecular mechanisms involved in the regulation of SMC differentiation and phenotypic modulation. J. Cell. Physiol. 231: 777–787, 2016. © 2015 Wiley Periodicals, Inc.
Phenolic Acid‐based Poly(anhydride‐esters) as Antioxidant Biomaterials
Authors: Prudencio Almudena , Faig Jonathan J. , Song MinJung , Uhrich Kathryn E.
Published: October 2015

Poly(anhydride‐esters) comprised of naturally occurring, non‐toxic phenolic acids, namely syringic and vanillic acid, with antioxidant properties were prepared via solution polymerization methods. Polymer and polymer precursor physiochemical properties were characterized, including polymer molecular weight and thermal properties. In vitro release studies illustrated that polymer hydrolytic degradation was influenced by relative hydrophobicity and degree of methoxy substitution of the phenolic acids. Further, the released phenolic acids were found to maintain antioxidant potency relative to free phenolic acid controls as determined by a 2,2‐diphenyl‐1‐picrylhydrazyl assay. Polymer cytotoxicity was assessed with L929 fibroblasts in polymer‐containing media; appropriate cell morphology and high fibroblast proliferation were obtained for the polymers at the lower concentrations. These polymers deliver non‐cytotoxic levels of naturally occurring antioxidants, which could be efficacious in topical delivery of antioxidant therapies.
The effects of carbon nanotube waviness and aspect ratio on the buckling behavior of functionally graded nanocomposite plates using a meshfree method
Authors: Shams Shahrooz , Soltani Behzad
Published: October 2015

This work deals with the effects of waviness and aspect ratio on the buckling behavior of functionally graded carbon nanotube‐reinforced composite (FG‐CNTRC) plates subjected to in‐plane loads using reproducing kernel particle method (RKPM) based on modified first‐order shear deformation theory (FSDT). Wavy single‐walled carbon nanotubes (CNTs) are embedded in a polymer matrix and distributed in four types of distributions. The material properties of an FG‐CNTRC plate are assumed to be graded along the thickness direction of the plate and estimated through a micromechanical model based on the extended rule of mixture. The modified shear correction factors evaluated involving the nonuniform shear stress distribution through the thickness of the FG‐CNTRC plate. For the imposition of the essential boundary conditions the full transformation approach is utilized. The validity and accuracy of the RKPM method is established by a comparison with the obtained results of available literature data. Moreover, the effects of distribution, volume fraction, waviness, and aspect ratio of CNTs are investigated on the buckling behavior of FG‐CNTRC plates for various boundary conditions, plate width‐to‐thickness and aspect ratios. Detailed parametric studies demonstrate that the waviness and aspect ratio of CNTs have noticeable effects on buckling behavior of carbon nanotube‐reinforced composite (CNTRC) plates. POLYM. COMPOS., 38:E531–E541, 2017. © 2015 Society of Plastics Engineers
The impact of a cancer diagnosis on health and well‐being: a prospective, population‐based study
Authors: Williams Kate , Jackson Sarah E. , Beeken Rebecca J. , Steptoe Andrew , Wardle Jane
Published: October 2015

Objective

Little is known about the trajectory of health and well‐being from before to after a cancer diagnosis. This study aimed to examine changes in health and well‐being across three time points (0–2 years before a cancer diagnosis, 0–2 years post‐diagnosis and 2–4 years post‐diagnosis) in individuals receiving a new cancer diagnosis, and at matched time points in a cancer‐free comparison group.

Methods

Data were from waves 1–6 of the English Longitudinal Study of Ageing. Repeated‐measures ANOVAs were used to examine differences in self‐rated health, mobility impairments, activities of daily living impairments, quality of life, depressive symptoms and life satisfaction by group and time, and group‐by‐time interactions.

Results

Of the 4565 participants with data from three time points, 444 (9.7%) reported a new cancer diagnosis. Those in the cancer group reported poorer self‐rated health (p < .001), quality of life (p < .001) and life satisfaction (p < .01) than participants in the comparison group, and a higher proportion reported depressive symptoms (p < .001) and impairments in mobility (p < .001) and activities of daily living (p < .001). All markers of health and well‐being worsened significantly over time. The group‐by‐time interaction was significant for self‐rated health (p < .001), with a greater decline in health over time in the cancer group.

Conclusions

Cancer survivors in this sample had poorer health and well‐being than those with no diagnosis, and self‐rated health deteriorated more rapidly following a cancer diagnosis. Screening for these factors around the time of a cancer diagnosis could allow for interventions to be targeted effectively and improve the health and well‐being of cancer survivors. © 2015 The Authors. Psycho‐Oncology published by John Wiley & Sons Ltd.
Crystal structure of the Legionella pneumophila lem10 effector reveals a new member of the HD protein superfamily
Authors: Morar Mariya , Evdokimova Elena , Chang Changsoo , Ensminger Alexander W. , Savchenko Alexei
Published: October 2015

Legionella pneumophila, the intracellular pathogen that can cause severe pneumonia known as Legionnaire's disease, translocates close to 300 effectors inside the host cell using Dot/Icm type IVB secretion system. The structure and function for the majority of these effector proteins remains unknown. Here, we present the crystal structure of the L. pneumophila effector Lem10. The structure reveals a multidomain organization with the largest C‐terminal domain showing strong structural similarity to the HD protein superfamily representatives. However, Lem10 lacks the catalytic His‐Asp residue pair and does not show any in vitro phosphohydrolase enzymatic activity, typical for HD proteins. While the biological function of Lem10 remains elusive, our analysis shows that similar distinct features are shared by a significant number of HD domains found in Legionella proteins, including the SidE family of effectors known to play an important role during infection. Taken together our data point to the presence of a specific group of non‐catalytic Legionella HD domains, dubbed LHDs, which are involved in pathogenesis. Proteins 2015; 83:2319–2325. © 2015 Wiley Periodicals, Inc.
Extending DerSimonian and Laird's methodology to perform network meta‐analyses with random inconsistency effects
Authors: Jackson Dan , Law Martin , Barrett Jessica K. , Turner Rebecca , Higgins Julian P. T. , Salanti Georgia , White Ian R.
Published: October 2015

Network meta‐analysis is becoming more popular as a way to compare multiple treatments simultaneously. Here, we develop a new estimation method for fitting models for network meta‐analysis with random inconsistency effects. This method is an extension of the procedure originally proposed by DerSimonian and Laird. Our methodology allows for inconsistency within the network. The proposed procedure is semi‐parametric, non‐iterative, fast and highly accessible to applied researchers. The methodology is found to perform satisfactorily in a simulation study provided that the sample size is large enough and the extent of the inconsistency is not very severe. We apply our approach to two real examples. © 2015 The Authors. Statistics in Medicine Published by John Wiley & Sons Ltd.
Misspecified poisson regression models for large‐scale registry data: inference for ‘largenand smallp’
Authors: Grøn Randi , Gerds Thomas A. , Andersen Per K.
Published: October 2015

Poisson regression is an important tool in register‐based epidemiology where it is used to study the association between exposure variables and event rates. In this paper, we will discuss the situation with ‘largenand smallp’, wherenis the sample size andpis the number of available covariates. Specifically, we are concerned with modeling options when there are time‐varying covariates that can have time‐varying effects. One problem is that tests of the proportional hazards assumption, of no interactions between exposure and other observed variables, or of other modeling assumptions have large power due to the large sample size and will often indicate statistical significance even for numerically small deviations that are unimportant for the subject matter. Another problem is that information on important confounders may be unavailable. In practice, this situation may lead to simple working models that are then likely misspecified. To support and improve conclusions drawn from such models, we discuss methods for sensitivity analysis, for estimation of average exposure effects using aggregated data, and a semi‐parametric bootstrap method to obtain robust standard errors. The methods are illustrated using data from the Danish national registries investigating the diabetes incidence for individuals treated with antipsychotics compared with the general unexposed population. Copyright © 2015 John Wiley & Sons, Ltd.
Basic‐Level Categories, Mirror Neurons, and Joint‐Attention Schemes: Three Points of Intersection Between G.H. Mead and Cognitive Science
Authors: McVeigh Ryan
Published: October 2015

Recent research in cognitive science has provided broad empirical support for the model of cognition and self‐development formulated by G.H. Mead. This is demonstrated specifically through three distinct cognitive mechanisms: basic‐level categories, mirror neurons, and joint‐attention schemes. These mechanisms illustrate a form of embodied sociality that underscores the intersubjective foundation of mind and self articulated by Mead. Research on basic‐level categories, mirror neurons, and joint‐attention schemes further extends Mead's relevance outside standard sociological and social psychological circles to the field of cognitive science and its emerging focus on sociality and social interaction.
Receptor Dissociation and B-Cell Activation
Authors: Yang Jianying , Reth Michael
Published: October 2015

The B-cell antigen receptor (BCR) is one of the most abundant receptors on the surface of B cells with roughly 100,000–200,000 copies per cell. Signaling through the BCR is crucial for the activation and differentiation of B cells. Unlike other receptors, the BCR can be activated by a large set of structurally different ligands, but the molecular mechanism of BCR activation is still a matter of controversy. Although dominant for a long time, the cross-link model (CLM) of BCR activation is not supported by recent studies of the nanoscale organization of the BCR on the surface of resting B cells. In contrast to the prediction of CLM, the numerous BCR complexes on these cells are not randomly distributed monomers but rather form oligomers which reside within membrane confinements. This finding is more in line with the dissociation activation model (DAM), wherein B-cell activation is accompanied by an opening of the auto-inhibited BCR oligomers instead of a cross-linking of the BCR monomers. In this review, we discuss in detail the new findings and their implications for BCR signaling.
An Extended Age-Hardening Model for Al-Mg-Si Alloys Incorporating the Room-Temperature Storage and Cold Deformation Process Stages
Authors: Myhr Ole Runar , Grong Øystein , Schäfer Carmen
Published: October 2015

In this article, a new age-hardening model for Al-Mg-Si alloys is presented (named NaMo-Version 2), which takes into account the combined effect of cold deformation and prolonged room-temperature storage on the subsequent response to artificial aging. As a starting point, the original physical framework of NaMo-Version 1 is revived and used as a basis for the extension. This is permissible, since a more in-depth analysis of the underlying particle-dislocation interactions confirms previous expectations that the simplifying assumption of spherical precipitates is not crucial for the final outcome of the calculations, provided that the yield strength model is calibrated against experimental data. At the same time, the implementation of the Kampmann–Wagner formalism means that the different microstructure models can be linked together in a manner that enforces solute partitioning and competition between the different hardening phases which form during aging (e.g., clusters, β″ and β′). In a calibrated form, NaMo-Version 2 exhibits a high degree of predictive power, as documented by comparison with experiments, using both dedicated nanostructure and yield strength data as a basis for the validation. Hence, the model is deemed to be well-suited for simulation of thermomechanical processing of Al-Mg-Si alloys involving cold-working operations like sheet forming and stretch bending in combination with heat treatment and welding.
Phase Transitions of Nonionic Surfactant C18:1E10 in Mixed Media of Water with Ionic Liquids
Authors: Wang Zhongni , Guan Lushi
Published: October 2015

Complicated temperature‐induced phase transitions were shown in two hexagonal liquid crystal mesophases constructed by nonionic surfactant C18:1E10 in the media of water with ionic liquids, 1‐butyl‐3‐methylimidazolium tetrofluoroborate (bmim‐BF4) and 1‐butyl‐3‐methylimidazolium hexafluorophosphate (bmim‐PF6), respectively. Detailed phase transition information was extracted from rheological, polarized optical microscopy, deuterium magnetic resonance spectroscopy and small‐angle X‐ray scattering measurements, with good agreement among these techniques. It is shown that the order‐to‐disorder phase transition occurred in a narrow range of temperatures for both the two hexagonal mesophases. In particular, the mesophases experienced a biphasic hexagonal‐lamellar coexisting before completely melting, which was not found in the corresponding aqueous hexagonal system of the same surfactant concentration. Of most importance, the two target mesophases exhibited some clearly different behaviors. The phase transition temperature is much higher (ca. 10 °C) in a (water + bmim‐BF4) system than in a (water + bmim‐PF6) system. After melting, a fast transition from elastic micelle to Newtonian fluid was observed in the (water + bmim‐BF4) system, while the micelle related to the (water + bmim‐PF6) system remained elastic over a relatively wide temperature region. The results obtained give a better insight of how the mixed solvents support mesophase formation and modulate the phase transition.
Production of Palm‐Based Esteramine Through Heterogeneous Catalysis
Authors: Aziz Haliza Abdul , Aroua Mohamed Kheireddine , Yusoff Rozita , Abas Noor Azeerah , Idris Zainab , Hassan Hazimah Abu
Published: October 2015

This study involved maximizing the conversion of palm‐based methyl palmitate to esteramine, an intermediate for esterquats via transesterification with triethanolamine, aided by Ca–Al as a heterogeneous catalyst in a 500‐ml reaction unit. The effect of process parameters on the conversion was investigated. The optimum process parameters, consisting of a mole ratio of 1.8:1 (methyl palmitate:triethanolamine), 170 °C, 10 mbar, 0.5 % catalyst and a duration of 2 h, produced more than 90 % conversion. Transesterification employing Ca–Al is more environmentally friendly than the conventional approach using sodium methoxide, simplifies the downstream separation process and the reusability of the catalyst was successfully tested in three subsequent cycles.
First record of buccinid genusChauvetia(Mollusca: Gastropoda) from the fossil record of the New World (Miocene, Venezuela) and its paleobiogeographic implications
Authors: Landau Bernard , da Silva Carlos M. , Vermeij Geerat J.
Published: October 2015

Until now, the buccinid genusChauvetiawas considered of European or West African origin, and is still endemic to these areas today. This paper describes the oldest representative of the genus,Chauvetia inopinatanov. sp., from the upper Burdigalian-lower Langhian transition Cantaure Formation of Venezuela. This surprising record suggests a New World tropical origin to the genus and subsequent immigration to the Old World before the earliest known Old World record, which is upper Tortonian. We postulate that this pre-late Tortonian (pre-8.12–7.42 Ma) dispersal of the tropical Gatunian west-AtlanticChauvetiainto the tropical East Atlantic European-West African Province most probably happened during the 10.71–9.36 Ma interval (early–mid Tortonian) during which the Circum-Tropical Current weakened, and the northward Intra-Caribbean Current had started, enhancing the Gulf Stream and the North Atlantic Current. This new data constitutes compelling evidence of a pre-Pliocene eastward dispersal of New World shallow marine organisms across the Atlantic.
Dynamic conceptualizations of threat in obsessive-compulsive disorder (OCD)
Authors: KNAPTON OLIVIA
Published: October 2015

abstract

Obsessive-compulsive disorder (OCD) is a severe mental health problem of a heterogeneous nature. To add to discussions around defining coherent subtypes of OCD, this paper uses qualitative, cognitive linguistic analysis to show how episodes of OCD can be differentiated based on their underlying conceptualizations of threat. Spoken narratives of OCD episodes told by people with OCD were analyzed using image schema theory and cognitive approaches to deixis in discourse. Through an exploration of the participants’ subjective experiences of time, space, and uncertainty in their recounted OCD episodes, the findings demonstrate that perceptions of threats fluctuate as OCD episodes unfold, and that it is the perceived movement (or not) of the threat that induces distress. Moreover, the dynamism of the threat is conceptualized differently for different subtypes of OCD. This variation can in part be explained by the role of two image schemas in structuring OCD episodes: the SOURCE–PATH–GOAL image schema and the CONTAINER image schema. It is argued that the blanket notion of threat as often investigated in clinical models of OCD is not sensitive enough to capture these shifting perspectives. It is thus recommended that threat perception in OCD is researched as a dynamic, evolving, and highly subjective experience.
Maiasaura, a model organism for extinct vertebrate population biology: a large sample statistical assessment of growth dynamics and survivorship
Authors: Woodward Holly N. , Freedman Fowler Elizabeth A. , Farlow James O. , Horner John R.
Published: October 2015

Fossil bone microanalyses reveal the ontogenetic histories of extinct tetrapods, but incomplete fossil records often result in small sample sets lacking statistical strength. In contrast, a histological sample of 50 tibiae of the hadrosaurid dinosaurMaiasaura peeblesorumallows predictions of annual growth and ecological interpretations based on more histologic data than any previous large sample study. Tibia length correlates well (R2>0.9) with diaphyseal circumference, cortical area, and bone wall thickness, thereby allowing longitudinal predictions of annual body size increases based on growth mark circumference measurements. With an avian level apposition rate of 86.4 μm/day,Maiasauraachieved over half of asymptotic tibia diaphyseal circumference within its first year. Mortality rate for the first year was 89.9% but a seven year period of peak performance followed, when survivorship (mean mortality rate=12.7%) was highest. During the third year of life,Maiasauraattained 36% (x=1260 kg) of asymptotic body mass, growth rate was decelerating (18.2 μm/day), cortical vascular orientation changed, and mortality rate briefly increased. These transitions may indicate onset of sexual maturity and corresponding reallocation of resources to reproduction. Skeletal maturity and senescence occurred after 8 years, at which point the mean mortality rate increased to 44.4%. Compared withAlligator, an extant relative,Maiasauraexhibits rapid cortical increase early in ontogeny, whileAlligatorcortical growth is much lower and protracted throughout ontogeny. Our life history synthesis ofMaiasaurautilizes the largest histological sample size for any extinct tetrapod species thus far, demonstrating how large sample microanalyses strengthen paleobiological interpretations.
Dietary intake and food sources of choline in European populations
Authors: Vennemann Francy B. C. , Ioannidou Sofia , Valsta Liisa M. , Dumas Céline , Ocké Marga C. , Mensink Gert B. M. , Lindtner Oliver , Virtanen Suvi M. , Tlustos Christina , D’Addezio Laura , Mattison Irene , Dubuisson Carine , Siksna Inese , Héraud Fanny
Published: October 2015

Choline is an important nutrient for humans. Choline intake of the European population was assessed considering the European Food Safety Authority European Comprehensive Food Consumption Database and the United States Department of Agriculture Nutrient Database. Average choline intake ranges were 151–210 mg/d among toddlers (1 to ≤3 years old), 177–304 mg/d among other children (3 to ≤10 years old), 244–373 mg/d among adolescents (10 to ≤18 years old), 291–468 mg/d among adults (18 to ≤65 years old), 284–450 mg/d among elderly people (65 to ≤75 years old) and 269–444 mg/d among very elderly people (≥75 years old). The intakes were higher among males compared with females, mainly due to larger quantities of food consumed per day. In most of the population groups considered, the average choline intake was below the adequate intake (AI) set by the Institute of Medicine in the USA. The main food groups contributing to choline intake were meat, milk, grain, egg and their derived products, composite dishes and fish. The main limitations of this study are related to the absence of choline composition data of foods consumed by the European population and the subsequent assumption made to assess their intake levels. Given the definition of AI, no conclusion on the adequacy of choline intake can be drawn for most European population groups. Such results improve the knowledge on choline intake in Europe that could be further refined by the collection of choline composition data for foods as consumed in Europe.
A NOTE ON THE CONSTRUCTION OF THE EQUILATERAL TRIANGLE WITH SCALENE ELEMENTARY TRIANGLES IN PLATO'S TIMAEUS: PL. TI. 54A-B
Authors: Paparazzo Ernesto
Published: October 2015

In the Timaeus Plato says that, among the infinite number of right-angled scalene elementary triangles, the best (τὸ κάλλιστον) is that

ἐξ οὗ τὸ ἰσόπλευρον ἐκ τρίτου συνέστηκε.

Apart from few exceptions to be mentioned shortly, the translations of the Timaeus, which I am aware of spanning the period from the second half of the nineteenth century up to recent times, have usually rendered this passage as meaning that such an elementary triangle is that which, when two are combined, the equilateral triangle forms as a third figure. For instance, Bury and Zeyl respectively translate:

out of which, when two are conjoined, the equilateral triangle is constructed as a third.

and

from [a pair of] which the equilateral triangle is constructed as a third figure.

I shall refer to this sort of translation as the Prevailing Translation (hereafter PT).
SOCRATES AND SELF-KNOWLEDGE IN ARISTOPHANES'CLOUDS
Authors: Moore Christopher
Published: October 2015

This article argues that Aristophanes'Cloudstreats Socrates as distinctly interested in promoting self-knowledge of the sort related to self-improvement. Section I shows that Aristophanes links the precept γνῶθι σαυτόν (‘know yourself’) with Socrates. Section II outlines the meaning of that precept for Socrates. Section III describes Socrates' conversational method in theCloudsas aimed at therapeutic self-revelation. Section IV identifies the patron Cloud deities of Socrates' school as also concerned to bring people to a therapeutic self-understanding, albeit in a different register from that of Socrates. Section V discusses a sequence of jokes connected to ‘stripping’ that give a concrete image to the search for self-knowledge. Both the action of the Clouds and the tales of cloak-stripping provide models for understanding self-knowledge in a Socratic key. Section VI argues that Socrates' other interest in thephrontistērion, myth-rationalization, is consistent with the promotion of self-knowledge. Section VII supports the claim that Plato'sPhaedrusalludes constantly to theClouds, and because thePhaedruspays careful attention to self-knowledge, Plato must think that theCloudsdoes too. It notes in particular that we can explain the Platonic Socrates' famous self-knowledge-related curiosity about his similarity to Typhon (230a) as Plato's allusion to Aristophanes, an allusion made apt by Aristophanes' coordination of Socrates with self-knowledge. Section VIII concludes the paper.