bluuebunny/crossref_metadata_2025 huggingface dataset:
ChemInform Abstract: Cosolvent‐Free Sol—Gel Synthesis and Optical Characterization of Silica Glasses Containing LaF3 and (La,Er)F3 Nanocrystals
Authors: Suzuki Kotomi , Kajihara Koichi , Kanamura Kiyoshi
Published: September 2014

Review: 49 refs.
Phase 2 trial of high‐dose rituximab with high‐dose cytarabine mobilization therapy and high‐dose thiotepa, busulfan, and cyclophosphamide autologous stem cell transplantation in patients with central nervous system involvement by non‐Hodgkin lymphoma
Authors: Chen Yi‐Bin , Batchelor Tracy , Li Shuli , Hochberg Ephraim , Brezina Mark , Jones Sooae , Del Rio Candice , Curtis Morgan , Ballen Karen K. , Barnes Jeffrey , Chi Andrew S. , Dietrich Jorg , Driscoll Jessica , Gertsner Elizabeth R. , Hochberg Fred , LaCasce Ann S. , McAfee Steven L. , Spitzer Thomas R. , Nayak Lakshmi , Armand Philippe
Published: September 2014

BACKGROUND

High‐dose thiotepa, busulfan, and cyclophosphamide (TBC) with autologous stem cell transplantation (ASCT) has been used in patients with central nervous system (CNS) involvement by non‐Hodgkin lymphoma (NHL). Despite limited penetration into the CNS, rituximab is active in primary CNS NHL. Therefore, high‐dose rituximab was combined with TBC for ASCT in patients with CNS NHL.

METHODS

A single‐arm phase 2 trial using high‐dose rituximab with cytarabine for stem cell mobilization followed by high‐dose rituximab combined with thiotepa, busulfan, and cyclophosphamide (R‐TBC) for ASCT was conducted. Doses of rituximab at 1000 mg/m2 were given on days 1 and 8 of mobilization and on days −9 and −2 of TBC. The primary endpoint was efficacy.

RESULTS

Thirty patients were enrolled. Eighteen patients had primary CNS NHL (12 with complete remission (CR)/first partial remission (PR1) and 6 with CR/PR2), and 12 patients had secondary CNS lymphoma (5 with CR/PR1 and 7 with CR/PR2 or beyond). All patients were in partial or complete remission. Twenty‐nine patients proceeded to R‐TBC ASCT. Two patients developed significant neurotoxicity. The 100‐day nonrelapse mortality rate was 0%, and 1 patient died because of nonrelapse causes 5 months after ASCT. For all patients, at a median follow‐up of 24 months (range, 12‐40 months), the estimated 2‐year progression‐free survival rate was 81% (95% confidence interval, 59%‐92%), and the 2‐year overall survival rate was 93% (95% confidence interval, 76%‐98%). There were no relapses or deaths among the 18 patients with primary CNS lymphoma.

CONCLUSIONS

For patients with CNS involvement by B‐cell NHL and especially for patients with primary CNS NHL, R‐TBC ASCT shows encouraging activity and merits further study. Cancer 2015;121:226–33. © 2014 American Cancer Society.
Blister Patterns and Energy Minimization in Compressed Thin Films on Compliant Substrates
Authors: Bedrossian Jacob , Kohn Robert V.
Published: September 2014

This paper is motivated by the complex blister patterns sometimes seen in thin elastic films on thick, compliant substrates. These patterns are often induced by an elastic misfit that compresses the film. Blistering permits the film to expand locally, reducing the elastic energy of the system. It is therefore natural to ask: what is the minimum elastic energy achievable by blistering on a fixed area fraction of the substrate? This is a variational problem involving both the elastic deformation of the film and substrate and the geometry of the blistered region. It involves three small parameters: the nondimensionalized thickness of the film, the compliance ratio of the film/substrate pair, and the mismatch strain. In formulating the problem, we use a small‐slope (Föppl–von Kármán) approximation for the elastic energy of the film, and a local approximation for the elastic energy of the substrate.

For a one‐dimensional version of the problem, we obtain “matching” upper and lower bounds on the minimum energy, in the sense that both bounds have the same scaling behavior with respect to the small parameters. The upper bound is straightforward and familiar: it is achieved by periodic blistering on a specific length scale. The lower bound is more subtle, since it must be proved without any assumption on the geometry of the blistered region.

For a two‐dimensional version of the problem, our results are less complete. Our upper and lower bounds only “match” in their scaling with respect to the nondimensionalized thickness, not in the dependence on the compliance ratio and the mismatch strain. The lower bound is an easy consequence of our one‐dimensional analysis. The upper bound considers a two‐dimensional lattice of blisters and uses ideas from the literature on the folding or “crumpling” of a confined elastic sheet. Our main two‐dimensional result is that in a certain parameter regime, the elastic energy of this lattice is significantly lower than that of a few large blisters. © 2015 Wiley Periodicals, Inc.
Unveiling the performance‐energy trade‐off in iterative linear system solvers for multithreaded processors
Authors: Aliaga José I. , Anzt Hartwig , Castillo Maribel , Fernández Juan C. , León Germán , Pérez Joaquín , Quintana‐Ortí Enrique S.
Published: September 2014

In this paper, we analyze the interactions occurring in the triangle performance‐power‐energy for the execution of a pivotal numerical algorithm, the iterative conjugate gradient (CG) method, on a diverse collection of parallel multithreaded architectures. This analysis is especially timely in a decade where the power wall has arisen as a major obstacle to build faster processors. Moreover, the CG method has recently been proposed as a complement to the LINPACK benchmark, as this iterative method is argued to be more archetypical of the performance of today's scientific and engineering applications. To gain insights about the benefits of hands‐on optimizations we include runtime and energy efficiency results for both out‐of‐the‐box usage relying exclusively on compiler optimizations, and implementations manually optimized for target architectures, that range from general‐purpose and digital signal multicore processors to manycore graphics processing units, all representative of current multithreaded systems. Copyright © 2014 John Wiley & Sons, Ltd.
Gas‐Phase Reaction of CeV2O7+ with C2H4: Activation of CC and CH Bonds
Authors: Ma Jia‐Bi , Yuan Zhen , Meng Jing‐Heng , Liu Qing‐Yu , He Sheng‐Gui
Published: September 2014

The reactivity of metal oxide clusters toward hydrocarbon molecules can be changed, tuned, or controlled by doping. Cerium‐doped vanadium cluster cations CeV2O7+ are generated by laser ablation, mass‐selected by a quadrupole mass filter, and then reacted with C2H4 in a linear ion trap reactor. The reaction is characterized by a reflectron time‐of‐flight mass spectrometer. Three types of reaction channels are observed: 1) single oxygen‐atom transfer , 2) double oxygen‐atom transfer , and 3) CC bond cleavage. This study provides the first bimetallic oxide cluster ion, CeV2O7+, which gives rise to CC bond cleavage of ethene. Neither CexOy± nor VxOy± alone possess the necessary topological and electronic properties to bring about such a reaction.
Ab Initio H2O in Realistic Hydrophilic Confinement
Authors: Allolio Christoph , Klameth Felix , Vogel Michael , Sebastiani Daniel
Published: September 2014

A protocol for the ab initio construction of a realistic cylindrical pore in amorphous silica, serving as a geometric nanoscale confinement for liquids and solutions, is presented. Upon filling the pore with liquid water at different densities, the structure and dynamics of the liquid inside the confinement can be characterized. At high density, the pore introduces long‐range oscillations into the water density profile, which makes the water structure unlike that of the bulk across the entire pore. The tetrahedral structure of water is also affected up to the second solvation shell of the pore wall. Furthermore, the effects of the confinement on hydrogen bonding and diffusion, resulting in a weakening and distortion of the water structure at the pore walls and a slowdown in diffusion, are characterized.
TERS Detection of αVβ3 Integrins in Intact Cell Membranes
Authors: Wang Hao , Schultz Zachary D.
Published: September 2014

Integrins are important membrane receptors that form focal adhesions with the extracellular matrix and are transmembrane signaling proteins. We demonstrate that nanoparticles functionalized with c‐RGDfC ligands bind to intact cell membranes and selectively enhance the amino acid signals of the integrin receptor when coupled with tip‐enhanced Raman scattering (TERS) detection. Controlling the plasmonic interaction between the functionalized nanoparticle and the TERS tip provides a clear Raman signal from αVβ3 integrins in the cell membrane that matches the signal of the purified integrin receptor. Random aggregation of nanoparticles on the cell does not provide the same spectral information. Chemical characterization of membrane receptors in intact cellular membranes is important for understanding membrane signaling and drug targeting. These results provide a new method to investigate the chemical interactions associated with ligand binding to membrane receptors in cells.
Caged Phosphate and the Slips and Misses in Determination of Quantum Yields for Ultraviolet‐A‐Induced Photouncaging
Authors: Anstaett Philipp , Leonidova Anna , Gasser Gilles
Published: September 2014

The quantum yields for photouncaging reactions are mostly determined relative to other uncaging reactions, often using 1‐(2‐nitrophenyl)ethyl‐phosphate (“caged phosphate”). Herein, we demonstrate that the quantum yields acquired by using this method can be off by an order of magnitude at the typical irradiation wavelengths around 350 nm and describe an easy‐to‐use alternative procedure using inexpensive azobenzene.
Enantioselective Oxidation of Thioethers to Sulfoxides by Means of a Structural Template with Chiral‐at‐Metal Ruthenium Complexes
Authors: Li Zheng‐Zheng , Yao Su‐Yang , Ye Bao‐Hui
Published: September 2014

Treatment of cis‐[Ru(bpy)2Cl2]⋅2 H2O or Δ/Λ‐[Ru(bpy)2(py)2]2+ (bpy=2,2′‐bipyridine, py=pyridine) with the prochiral thioether ligands 2‐alkylthiobenzoic acid (HOSR) produces the corresponding thioether complexes rac‐[Ru(bpy)2(OSR)](PF6) (R=Me (rac‐1), iPr (rac‐2), 2‐benzylthiobenzonate (Bn) (rac‐3)) and Δ/Λ‐[Ru(bpy)2(OSR)](PF6) (R=Me (Δ‐1/Λ‐1), iPr (Δ‐2/Λ‐2), Bn (Δ‐3/Λ‐3)) with retention of the configurations at chiral metal centers. In situ oxidation of the thioether complexes by meta‐chloroperoxybenzoic acid provides the corresponding sulfoxide complexes rac‐[Ru(bpy)2(OSOR)](PF6) (OSOR is 2‐alkylsulfinylbenzonate, R=Me (rac‐1 a), iPr (rac‐2 a), Bn (rac‐3 a)), Δ‐[Ru(bpy)2{(R)‐OSOR}](PF6) (R=Me (Δ‐1 a), iPr (Δ‐2 a), Bn (Δ‐3 a)), and Λ‐[Ru(bpy)2{(S)‐OSOR}](PF6) (R=Me (Λ‐1 a), iPr (Λ‐2 a), Bn (Λ‐3 a)) in yields of 95 % with 98 % ee values. The absolute configurations at the metal centers and sulfur atoms were determined by means of X‐ray crystallography. The results indicate that the configurations of the metal centers are retained and have the function of controlling sulfoxide chirality during the oxidation process. The Δ metal‐centered configuration enantioselectively generates an R‐configuration sulfoxide, and the Λ configuration enantioselectively forms an S‐configuration sulfoxide in the course of the in situ oxidation reaction, thereby resulting in a predetermined chirality of the sulfoxide ligands. The predetermined chirality of sulfoxides (S)‐HOSOR and (R)‐HOSOR were obtained by the treatments of the corresponding sulfoxide complexes Δ‐[Ru(bpy)2{(R)‐OSOR}](PF6) and Λ‐[Ru(bpy)2{(S)‐OSOR}](PF6) with trifluoroacetic acid in yields of 90 % with 83.5–92.9 % ee values.
Synthesis of PdO‐ZnO mixed oxide precursors for PdZn intermetallic catalysts
Authors: Paiz Jonathan , Fitch James , Peterson Eric , Hough Tyler , Barnard Werner , Datye Abhaya
Published: September 2014

PdZn mixed oxides are precursors for the formation of intermetallic PdZn phases, which show improved catalytic performance for methanol steam reforming. In this work we have prepared mixed oxides (PdxZn1‐xO) that span a range of compositions around the tetragonal PdZn 1:1 L10 phase (x = 0.25, 0.5 and 0.75). We find that Pd+2 can be isomorphously substituted into hexagonal ZnO and likewise Zn+2 can also be substituted within tetragonal PdO. Our results show that the mixed oxide has a composition Pd0.75Zn0.25O within the tetragonal PdO lattice with a slight contraction in unit cell volume. The results are relevant for understanding the enhanced sensing properties of ZnO and the nature of the oxide precursors for the synthesis of intermetallic PdZn nanoparticles for heterogeneous catalysis.
Metal–Nitrogen Doping of Mesoporous Carbon/Graphene Nanosheets by Self‐Templating for Oxygen Reduction Electrocatalysts
Authors: Li Shuang , Wu Dongqing , Liang Haiwei , Wang Jinzuan , Zhuang Xiaodong , Mai Yiyong , Su Yuezeng , Feng Xinliang
Published: September 2014

We demonstrate a general and efficient self‐templating strategy towards transition metal–nitrogen containing mesoporous carbon/graphene nanosheets with a unique two‐dimensional (2D) morphology and tunable mesoscale porosity. Owing to the well‐defined 2D morphology, nanometer‐scale thickness, high specific surface area, and the simultaneous doping of the metal–nitrogen compounds, the as‐prepared catalysts exhibits excellent electrocatalytic activity and stability towards the oxygen reduction reaction (ORR) in both alkaline and acidic media. More importantly, such a self‐templating approach towards two‐dimensional porous carbon hybrids with diverse metal–nitrogen doping opens up new avenues to mesoporous heteroatom‐doped carbon materials as electrochemical catalysts for oxygen reduction and hydrogen evolution, with promising applications in fuel cell and battery technologies.
A framework for high‐speed parallel‐prefix adder performance evaluation and comparison
Authors: Hobson Richard F.
Published: September 2014

A new framework is proposed for the evaluation and comparison of high‐speed parallel‐prefix adders. The framework specifies input registers and latches and requires sum feedback for single cycle pipelined operation. Test pattern generation is also specified. A newly revised energy‐efficient 64‐bit carry select adder with distributed mixed valence logic to help reduce fan‐out and wire load is presented. Footless pulsed‐precharge domino and compound domino circuits, and smaller transistors help to reduce area and power. Detailed simulations with 65 nm CMOS models are compared with other parallel‐prefix adders that have been instantiated for comparison. Within this framework, energy reductions of 40% are obtained for the new adder versus two leading Kogge‐Stone designs, and 25% versus a new constant delay logic Sklansky style design, at similar cycle times. Copyright © 2014 John Wiley & Sons, Ltd.
Context‐dependent latent inhibition in preweanling rats
Authors: Revillo D.A. , Gaztañaga M. , Aranda E. , Paglini M.G. , Chotro M.G. , Arias C.
Published: September 2014

Preexposure to a conditioned stimulus (CS) usually weakens conditioning, an effect known as latent inhibition. Similar to other learning interference effects, latent inhibition has been characterized as context‐dependent, which means that the magnitude of this effect can be attenuated by changing the context between the different phases of the procedure (e.g., preexposure and conditioning). Latent inhibition has been found with a variety of procedures in infant rats, but the few studies that examined the context‐dependency of this phenomenon during this ontogenetic period found no context‐change effect. The present study explored the context‐dependency of latent inhibition during infancy using a conditioned taste aversion preparation and employing contexts enriched with distinctive odors to increase the possible efficacy of the context manipulation. Experiment 1 showed that three preexposures to the CS (saccharin) were sufficient to retard conditioning to the same CS, although this effect was also observed in a control group preexposed to an alternative taste stimulus (saline), in comparison with a non‐preexposed control group. In Experiment 2a, the CS‐preexposure effect was found to be specific to the preexposed CS when the number of preexposures was increased. This effect was revealed as context‐dependent in Experiment 2b, since it was attenuated by changing the context between preexposure and conditioning. The present result is consistent with recent studies showing the context‐dependency of extinction in preweanling rats, thus demonstrating these animals' capacity to learn about context early on in their development. © 2014 Wiley Periodicals, Inc. Dev Psychobiol 56: 1507–1517, 2014.
Application of an LC‐MS/MS method to the pharmacokinetics of TM‐2, a potential antitumour agent, in rats
Authors: Men Lei , Zhao Yunli , Lin Hongli , Yang Mingjing , Liu Hui , Shao Yanjie , Fan Ronghua , Tang Xing , Yu Zhiguo
Published: September 2014

TM‐2 is a novel semi‐synthetic taxane derivative, selected for preclinical development based on its greater anticancer activity and lower toxicity compared with docetaxel. In this study, a rapid and sensitive analytical method based on ultra performance liquid chromatography‐tandem mass spectrometry (LC‐MS/MS) has been developed for the determination of TM‐2 in rat plasma. The biological samples were extracted with methyl tert‐butyl ether and separated on a C18 column (50 mm × 2.1 mm, 1.7 µm) using a mobile phase consisting of acetonitrile and 2 mM ammonium acetate. The standard curves were linear over the range 5–1000 ng/mL in rat plasma. The precision (relative standard deviation, RSD, %) were within 14.5%, and the accuracy (relative error, RE, %) ranged from −1.56 to 2.36%. Recovery and matrix effect were satisfactory in rat plasma. The validated method was successfully applied to pharmacokinetic studies after intravenous administration of TM‐2 to rats. The pharmacokinetics of TM‐2 in rats were characterized by a large volume of distribution and a long half‐life of elimination after single dose (4, 8, and 16 mg/kg), and a good correlation was observed between AUC and dose. The preclinical data will be useful for the design of subsequent trials of TM‐2. Copyright © 2014 John Wiley & Sons, Ltd.
T/B‐cell interactions are more transient in response to weak stimuli in SLE‐prone mice
Authors: Sinai Parisa , Dozmorov Igor M. , Song Ran , Schwartzberg Pamela L. , Wakeland Edward K. , Wülfing Christoph
Published: September 2014

Changes in immune function during the course of systemic lupus erythematosus (SLE) are well characterized. Class‐switched antinuclear antibodies are the hallmark of SLE, and T/B‐cell interactions are thus critical. However, changes in immune function contributing to disease susceptibility are unknown. Here, we have analyzed primary T and B cells from a mouse model of SLE prior to the onset of disease. To allow cognate T‐cell activation with low affinity, we have developed a lower potency peptide ligand for the OTII TCR. T‐ and B‐cell couples formed less frequently and retained their polarity less efficiently preferentially in response to low‐affinity stimulation in SLE‐prone mice. This matched decreased recruitment of actin and Vav1 and an enhanced PKCΘ recruitment to the cellular interface in T cells. The induction of the GC B‐cell marker GL7 was increased in T/B cell couples from SLE‐prone mice when the T‐cell numbers were limited. However, the overall gene expression changes were marginal. Taken together, the enhanced cell‐couple transience may allow a more efficient sampling of a large number of T/B cell couples, preferentially in response to limiting stimuli, therefore enhancing the immune reactivity in the development of SLE.
High‐resolution melt analysis of the minisatellite D1S80: A potential forensic screening tool
Authors: Pomeroy Robert S. , Balamurugan Kuppareddi , Wong Helena , Duncan George
Published: September 2014

High‐resolution melt (HRM) analysis of the VNTR region of the human D1S80 locus, a 16‐bp repeat minisatellite from approximately 400 to over 700 bp in length, was investigated. A Qiagen Rotor‐Gene Q using the Type‐it PCR HRM kit was used to acquire HRM curves for 14 single, and 16 biallelic, dsDNA samples. The HRM analysis was applicable over a range of DNA concentrations; however the characteristics of the melt curve did depend on the forward and reverse primer ratio. Despite the large amplicon size and the similarities of the repeat sequences, it was possible to discriminate different genotypes. Heterozygotes were clearly different from the homozygous variants and even small differences in the repeat sequence could be differentiated. However, the melt analysis requires a high‐resolution system with temperature resolution of 0.02°C or better in order to sort out differences in these large amplicons of near identical GC content (in this case 56%). HRM analysis of amplicons with large repeat sequences can be used as a means of comparing DNA fragments. Examination of multiple sequences can be used to differentiate DNA samples and demonstrate the potential of HRM analysis as a rapid and inexpensive prescreening technique in forensic applications.
Upgrading Carbon Dioxide/Methane Mixtures by using a Hybrid Membrane–Condensed Rotational Separation Process
Authors: van Kemenade H. P. , van Benthum R. J. , Brouwers J. J. H.
Published: September 2014

Membranes are used to upgrade heavily contaminated methane gas to pipeline specifications. However, the typical membrane process suffers from a considerable methane slip in the permeate flow. In the hybrid system considered in this Communication, the methane is removed from the permeate stream by using a low‐temperature distillation process with condensed rotational separation (CRS). Compared to a hybrid amine‐CRS process, the energy and volume use are reduced by a factor of two.
Gestational and Postpartum Weight Change Patterns in Mothers with Eating Disorders
Authors: Zerwas Stephanie C. , Von Holle Ann , Perrin Eliana M. , Cockrell Skinner Asheley , Reba‐Harrelson Lauren , Hamer Robert M. , Stoltenberg Camilla , Torgersen Leila , Reichborn‐Kjennerud Ted , Bulik Cynthia M.
Published: September 2014

Background

Although pregnancy can be associated with adaptive changes in weight and eating behaviour for women with eating disorders, less is known about whether these changes are maintained in the postpartum period. We used a longitudinal design to examine gestational and postpartum weight trajectories in mothers with and without eating disorders in the Norwegian Mother and Child Cohort Study (MoBa) conducted by the Norwegian Institute of Public Health.

Methods

Fifty‐six women reported anorexia nervosa (AN), 636 bulimia nervosa, 3327 binge eating disorder and 69 eating disorder not otherwise specified, purging type. The referent group included 61 233 mothers with no eating disorder. We used a mixed effects model to predict weight change over time by eating disorder subtype.

Results

Mothers with AN, bulimia nervosa, binge eating disorder and eating disorder not otherwise specified had greater increases in body mass index (BMI) during pregnancy and greater decreases in BMI over the first 6 months postpartum. Women with AN shifted from the underweight BMI range before pregnancy to the normal weight range at 36 months postpartum

Conclusions

Patterns of maternal weight gain and retention during the perinatal period vary across eating disorder subtype and warrant clinical attention. Copyright © 2014 John Wiley & Sons, Ltd and Eating Disorders Association.
Reaction‐to‐fire properties of polymer matrix composites with integrated intumescent barriers
Authors: Eibl Sebastian
Published: September 2014

The integration of an intumescent barrier between the plies of prepreg based polymer matrix composite and sandwich panels is investigated in detail with regard to reaction‐to‐fire properties. Incident heat flux, panel thickness and insertion depth within the panel were varied systematically. Fire retarding effects are compared to the application of an intumescent and top coating on the surface. All tests were carried out with a commercial material: HexPly® 8552/IM7 by Hexcel. Design rules for an effective improvement of reaction‐to‐fire properties are derived. Two practical applications were identified not interfering with mechanical properties: A metal mesh as support for the intumescent material underneath a single top ply and the one‐sided integration in a sandwich with the possibility to expand into the honeycomb. Degradation mechanisms are characterized by cone calorimetry and temperature development throughout the specimens. Copyright © 2014 John Wiley & Sons, Ltd.
Generalized Functional Linear Models for Gene‐Based Case‐Control Association Studies
Authors: Fan Ruzong , Wang Yifan , Mills James L. , Carter Tonia C. , Lobach Iryna , Wilson Alexander F. , Bailey‐Wilson Joan E. , Weeks Daniel E. , Xiong Momiao
Published: September 2014

By using functional data analysis techniques, we developed generalized functional linear models for testing association between a dichotomous trait and multiple genetic variants in a genetic region while adjusting for covariates. Both fixed and mixed effect models are developed and compared. Extensive simulations show that Rao's efficient score tests of the fixed effect models are very conservative since they generate lower type I errors than nominal levels, and global tests of the mixed effect models generate accurate type I errors. Furthermore, we found that the Rao's efficient score test statistics of the fixed effect models have higher power than the sequence kernel association test (SKAT) and its optimal unified version (SKAT‐O) in most cases when the causal variants are both rare and common. When the causal variants are all rare (i.e., minor allele frequencies less than 0.03), the Rao's efficient score test statistics and the global tests have similar or slightly lower power than SKAT and SKAT‐O. In practice, it is not known whether rare variants or common variants in a gene region are disease related. All we can assume is that a combination of rare and common variants influences disease susceptibility. Thus, the improved performance of our models when the causal variants are both rare and common shows that the proposed models can be very useful in dissecting complex traits. We compare the performance of our methods with SKAT and SKAT‐O on real neural tube defects and Hirschsprung's disease datasets. The Rao's efficient score test statistics and the global tests are more sensitive than SKAT and SKAT‐O in the real data analysis. Our methods can be used in either gene‐disease genome‐wide/exome‐wide association studies or candidate gene analyses.
Above the hoof: functional morphology of the fossil deer from Tegelen, the Netherlands
Authors: Alcalde Gema M. , van den Hoek Ostende Lars W.
Published: September 2014

Villafranchian faunas were widely spread throughout the European continent during the Plio‐Pleistocene. Ungulates, and particularly ruminants, are very well represented in most of the localities of this period. The fossil site of Tegelen (Province of Limburg, the Netherlands) is a classical Villafranchian locality where cervids are especially abundant. Some of the sites from this period have been thoroughly studied in various aspects, such as faunal assemblages, biochronology, magnetostratigraphy, sedimentology or palaeoenvironmental conditions, among others. Tegelen has been as well studied, but its particular exploitation has hampered its study for years. In order to reconstruct its prevailing palaeohabitat, we have applied statistical analyses based on functional morphology for the first time for this fossil site. In this work, we have analysed the ecomorphology of the postcranial skeleton of Eucladoceros ctenoides and Metacervoceros rhenanus, the two extinct species of deer present in Tegelen. Results show that the best ecological indicators are the metapods and the tibia, while the astragalus seems to be the least informative element. The analyses reveal likewise how both taxa show adaptations to both open and forest environments, but with a slight trend to the former. These results disagree with the general assumption that E. ctenoides and M. rhenanus are indicative of forested settings, as well as with the classical interpretations of the palaeoenvironment of Tegelen made to date, which are exclusively based on the fauna. However, they go along with the appearance of some taxa typical of open habitats, such as the micromammals Hystrix and Dicrostonyx, which could help to explain their enigmatic presence. Copyright © 2014 John Wiley & Sons, Ltd.
Connective tissue growth factor and integrin αvβ6: A new pair of regulators critical for ductular reaction and biliary fibrosis in mice
Authors: Pi Liya , Robinson Paulette M. , Jorgensen Marda , Oh Seh‐Hoon , Brown Alicia R. , Weinreb Paul H. , Trinh Thu Le , Yianni Protopapadakis , Liu Chen , Leask Andrew , Violette Shelia M. , Scott Edward W. , Schultz Gregory S. , Petersen Bryon E.
Published: September 2014

Connective tissue growth factor (CTGF) is a matricellular protein that mediates cell‐matrix interaction through various subtypes of integrin receptors. This study investigated the role of CTGF and integrin αvβ6 in hepatic progenitor/oval cell activation, which often occurs in the form of ductular reactions (DRs) when hepatocyte proliferation is inhibited during severe liver injury. CTGF and integrin αvβ6 proteins were highly expressed in DRs of human cirrhotic livers and cholangiocarcinoma. Confocal microscopy analysis of livers from Ctgf promoter‐driven green fluorescent protein reporter mice suggested that oval cells and cholangiocytes were the main sources of CTGF and integrin αvβ6 during liver injury induced by 3,5‐diethoxycarbonyl‐1,4‐dihydrocollidine (DDC). Deletion of exon 4 of the Ctgf gene using tamoxifen‐inducible Cre‐loxP system down‐regulated integrin αvβ6 in DDC‐damaged livers of knockout mice. Ctgf deficiency or inhibition of integrin αvβ6, by administrating the neutralizing antibody, 6.3G9 (10 mg/kg body weight), caused low levels of epithelial cell adhesion molecule and cytokeratin 19 gene messenger RNAs. Also, there were smaller oval cell areas, fewer proliferating ductular epithelial cells, and lower cholestasis serum markers within 2 weeks after DDC treatment. Associated fibrosis was attenuated, as indicated by reduced expression of fibrosis‐related genes, smaller areas of alpha‐smooth muscle actin staining, and low collagen production based on hydroxyproline content and Sirius Red staining. Finally, integrin αvβ6 could bind to CTGF mediating oval cell adhesion to CTGF and fibronection substrata and promoting transforming growth factor (TGF)‐β1 activation in vitro. Conclusions: CTGF and integrin αvβ6 regulate oval cell activation and fibrosis, probably through interacting with their common matrix and signal partners, fibronectin and TGF‐β1. CTGF and integrin αvβ6 are potential therapeutic targets to control DRs and fibrosis in related liver disease. (Hepatology 2015;61:678‐691)
Relationship Between Pretreatment Rate of Bone Loss and Bone Density Response to Once-Yearly ZOL: HORIZON-PFT Extension Study
Authors: Eastell Richard , Boonen Steven , Cosman Felicia , Reid Ian R , Palermo Lisa , Cummings Steven R , Black Dennis M
Published: September 2014

Several studies have shown that high bone turnover is associated with greater rates of bone loss and greater bone mineral density (BMD) response to antiresorptive therapy in postmenopausal osteoporosis. However, it is not known whether greater rates of bone loss before therapy are associated with greater BMD response to antiresorptive therapy. In the HORIZON-PFT study and its extension, one group of women who were randomized to receive placebo for 3 years (years 1, 2, and 3) were then switched to zoledronic acid (ZOL) 5 mg annually for up to three injections (years 4, 5, and 6, P3Z3 arm) (n = 1223). We measured total hip BMD at baseline, 1, 2, and 3 years on placebo and at 4.5 and 6 years on ZOL. The procollagen type I N-terminal propeptide (PINP) was measured at 3, 4.5, and 6 years. By design, not all subjects were followed for as long as 6 years, so this analysis focused on the results at 4.5 years. Those with the largest loss in total hip BMD on placebo in years 0 to 3 had the largest gain during ZOL (years 3 to 4.5): (r = –0.39, p < 0.0001). The change in total hip BMD in years 0 to 3 on placebo was related to the serum PINP at the end of the 3-year period (r = –0.24, p < 0.0001). The change in total hip BMD on ZOL from year 3 to 4.5 was related to the serum PINP at the end of the 3-year period (r = 0.26, p < 0.0001). We conclude that BMD response to ZOL is greater in postmenopausal women who had larger loss before treatment. This association may result from higher bone turnover being associated with both greater bone loss on placebo and greater BMD response to ZOL. © 2014 American Society for Bone and Mineral Research.
Sphingosine‐1‐Phosphate Mediates COX‐2 Expression and PGE2/IL‐6 Secretion via c‐Src‐Dependent AP‐1 Activation
Authors: Hsu Chih‐Kai , Lee I‐Ta , Lin Chih‐Chung , Hsiao Li‐Der , Yang Chuen‐Mao
Published: September 2014

Sphingosine‐1‐phosphate (S1P) has been shown to regulate cyclooxygenase‐2 (COX‐2)/prostaglandin E2(PGE2) expression and IL‐6 secretion in various respiratory diseases. However, the mechanisms underlying S1P‐induced COX‐2 expression and PGE2production in human tracheal smooth muscle cells (HTSMCs) remain unclear. Here we demonstrated that S1P markedly induced COX‐2 expression. S1P also induced PGE2and IL‐6 secretion which were reduced by the inhibitors of COX‐2 (NS‐398 and celecoxib). Pretreatment with the inhibitor of S1PR1 (W123), S1PR3 (CAY10444), c‐Src (PP1), PYK2 (PF431396), MEK1/2 (U0126), p38 MAPK (SB202190), JNK1/2 (SP600125), or AP‐1 (Tanshinone IIA) and transfection with siRNA of S1PR1, S1PR3, c‐Src, PYK2, p38, p42, JNK2, c‐Jun, or c‐Fos reduced S1P‐induced COX‐2 expression and PGE2/IL‐6 secretion. Moreover, S1P induced c‐Src, PYK2, p42/p44 MAPK, JNK1/2, p38 MAPK, and c‐Jun phosphorylation. We observed that S1P‐induced p42/p44 MAPK and JNK1/2, but not p38 MAPK activation was mediated via a c‐Src/PYK2‐dependent pathway. S1P also enhanced c‐Fos, but not c‐Jun mRNA and protein expression and the AP‐1 promoter activity. S1P‐induced c‐Fos mRNA and protein expression, c‐Jun phosphorylation, and AP‐1 promoter activity was reduced by W123, CAY10444, PP1, PF431396, U0126, SP600125, or SB202190. These results demonstrated that S1P‐induced COX‐2 expression and PGE2/IL‐6 generation was mediated through S1PR1/3/c‐Src/PYK2/p42/p44 MAPK‐ or JNK1/2‐ and S1PR1/3/c‐Src/p38 MAPK‐dependent AP‐1 activation. J. Cell. Physiol. 230: 702–715, 2015. © 2014 Wiley Periodicals, Inc., A Wiley Company
Review: Cell Dynamics in Malignant Pleural Effusions
Authors: Giarnieri Enrico , Bellipanni Gianfranco , Macaluso Marcella , Mancini Rita , Holstein Adam Carl , Milanese Carla , Giovagnoli Maria Rosaria , Giordano Antonio , Russo Giuseppe
Published: September 2014

Malignant pleural effusions (MPEs) are a common manifestation found in patients with lung cancer. After cytological and histological confirmation of malignancy, talc pleurodesis still remains the treatment of choice in patients with MPEs resistant to chemotherapy. Despite this, primary challenges include reduced quality of life and life expectancy in general. Therefore, a better understanding of the cell biology of MPEs, along with improvements in treatment is greatly needed. It has recently been demonstrated that MPEs may represent an excellent source for identification of molecular mechanisms within the tumor and its environment. The present review summarizes the current understanding of MPEs cells and tumor microenvironment, and particularly focuses on dissecting the cross‐talk between MPEs and epithelial to mesenchymal transition (EMT), inflammation and cancer stem cells. J. Cell. Physiol. 230: 272–277, 2015. © 2014 Wiley Periodicals, Inc.
Isoform‐Specific SCFFbw7 Ubiquitination Mediates Differential Regulation of PGC‐1α
Authors: Trausch‐Azar Julie S. , Abed Mona , Orian Amir , Schwartz Alan L.
Published: September 2014

The E3 ubiquitin ligase and tumor suppressor SCFFbw7 exists as three isoforms that govern the degradation of a host of critical cell regulators, including c‐Myc, cyclin E, and PGC‐1α. Peroxisome proliferator activated receptor‐gamma coactivator 1α (PGC‐1α) is a transcriptional coactivator with broad effects on cellular energy metabolism. Cellular PGC‐1α levels are tightly controlled in a dynamic state by the balance of synthesis and rapid degradation via the ubiquitin‐proteasome system. Isoform‐specific functions of SCFFbw7 are yet to be determined. Here, we show that the E3 ubiquitin ligase, SCFFbw7, regulates cellular PGC‐1α levels via two independent, isoform‐specific, mechanisms. The cytoplasmic isoform (SCFFbw7β) reduces cellular PGC‐1α levels via accelerated ubiquitin‐proteasome degradation. In contrast, the nuclear isoform (SCFFbw7α) increases cellular PGC‐1α levels and protein stability via inhibition of ubiquitin‐proteasomal degradation. When nuclear Fbw7α proteins are redirected to the cytoplasm, cellular PGC‐1α protein levels are reduced through accelerated ubiquitin‐proteasomal degradation. We find that SCFFbw7β catalyzes high molecular weight PGC‐1α‐ubiquitin conjugation, whereas SCFFbw7α produces low molecular weight PGC‐1α‐ubiquitin conjugates that are not effective degradation signals. Thus, selective ubiquitination by specific Fbw7 isoforms represents a novel mechanism that tightly regulates cellular PGC‐1α levels. Fbw7 isoforms mediate degradation of a host of regulatory proteins. The E3 ubiquitin ligase, Fbw7, mediates PGC‐1α levels via selective isoform‐specific ubiquitination. Fbw7β reduces cellular PGC‐1α via ubiquitin‐mediated degradation, whereas Fbw7α increases cellular PGC‐1α via ubiquitin‐mediated stabilization. J. Cell. Physiol. 230: 842–852, 2015. © 2014 Wiley Periodicals, Inc.
Osteoarthritis disease progression model using six year follow‐up data from the osteoarthritis initiative
Authors: Passey Chaitali , Kimko Holly , Nandy Partha , Kagan Leonid
Published: September 2014

The objective was to develop a quantitative model of disease progression of knee osteoarthritis over 6 years using the total WOMAC score from patients enrolled into the Osteoarthritis Initiative (OAI) study. The analysis was performed using data from the Osteoarthritis Initiative database. The time course of the total WOMAC score of patients enrolled into the progression cohort was characterized using non‐linear mixed effect modeling in NONMEM. The effect of covariates on the status of the disease and the progression rate was investigated. The final model provided a good description of the experimental data using a linear progression model with a common baseline (19 units of the total WOMAC score). The WOMAC score decreased by 1.77 units/year in 89% of the population or increased by 1.74 units/year in 11% of the population. Multiple covariates were found to affect the baseline and the rate of progression, including BMI, sex, race, the use of pain medications, and the limitation in activity due to symptoms. A mathematical model to describe the disease progression of osteoarthritis in the studied population was developed. The model identified two sub‐populations with increasing or decreasing total WOMAC score over time, and the effect of important covariates was quantified.
An argument for using additional bedside tools, such as bedside ultrasound, for volume status assessment in hospitalized medical patients: A needs assessment survey
Authors: Low David , Vlasschaert Meghan , Novak Kerri , Chee Alex , Ma Irene W. Y.
Published: September 2014

The frequency at which housestaff need to assess volume status on medical inpatients is unknown. In this brief report, we invited 39 housestaff, over 13 randomly selected dates, to complete a 25‐item survey. Participants (n = 31, 79%) logged a total of 455 hours, reporting 197 pages or telephone requests received regarding medical inpatients. Of these, 41 pages (21%) required a volume status assessment. Participants reported their volume status assessment competency to be moderate (median score = 3, interquartile range = 3 to 4, where 1 = not competent to perform independently and 6 = above average competence). In 9 of the 41 assessments (22%), at least 1 barrier was reported in determining volume status. The most commonly reported barriers were conflicting physical examination findings (n = 8, 20%) and suboptimal patient examination (n = 5, 12%). Over 20% of pages regarding admitted medical patients required volume status assessments by medical housestaff. Despite moderate self‐reported competence in the ability to assess volume status, barriers such as conflicting physical examination findings and suboptimal patient examinations were present in up to 20% of assessments. Therefore, we urge educators to consider incorporating bedside ultrasound training for volume status into the internal medicine curriculum. Journal of Hospital Medicine 2014;9:727–730. © 2014 Society of Hospital Medicine
Understanding how to improve collaboration between hospitals and primary care in postdischarge care transitions: A qualitative study of primary care leaders' perspectives
Authors: Nguyen Oanh Kieu , Kruger Jenna , Greysen S. Ryan , Lyndon Audrey , Goldman L. Elizabeth
Published: September 2014

BACKGROUND

There is limited collaboration between hospitals and primary care despite parallel efforts to improve postdischarge care transitions.

OBJECTIVE

To understand what primary care leaders perceived as barriers and facilitators to collaboration with hospitals.

METHODS

Qualitative study with in‐depth, semistructured interviews of 22 primary care leaders in 2012 from California safety‐net clinics.

RESULTS

Major barriers to collaboration included lack of institutional financial incentives for collaboration, competing priorities (e.g., regulatory requirements, strained clinic capacity, financial strain) and mismatched expectations about role and capacity of primary care to improve care transitions. Facilitators included relationship building through interpersonal networking and improving communication and information transfer via electronic health record (EHR) implementation.

CONCLUSIONS

Efforts to improve care transitions should focus on aligning financial incentives, standardizing regulations around EHR interoperability and data sharing, and enhancing opportunities for interpersonal networking. Journal of Hospital Medicine 2014;9:700–706. © 2014 Society of Hospital Medicine
Raman spectroscopy and chemometrics for quantitative analysis of complex flows in an industrial transesterification process
Authors: Filliung Aurélie , Chapron David , Bourson Patrice , Finqueneisel Gisèle , Riondel Alain , Guilment Jean
Published: September 2014

A method based on Raman spectroscopy has been used for determination of ester acrylate mixture composition from an industrial production of acrylic monomers. Five molecules of the industrial mixture have been studied: main components and an impurity. Experiments were carried out with an immersion probe on the spectral range of 100–3425 cm−1. Usually, monitoring a complex industrial flow by spectroscopic analysis requires a lot of samples in order to have a representative prediction model. Here only 60 samples from the process were necessary to build the model. The statistics was then artificially increased by synthetically increasing the number of samples. A qualitative study by principal component analysis was at first done, and then a partial least squares method was performed to assess the feasibility of quantitative measurements in such transesterification process. Internal and external validations methods have been used and their results show a RMSEP below 1% of samples predicted concentration ranges. The repeatability and reproducibility of Raman measurements are also discussed. Copyright © 2014 John Wiley & Sons, Ltd.
Protective effects of Cholestin on ethanol induced oxidative stress in rats
Authors: Hsieh You‐Liang , Yeh Yen‐Hung , Lee Ya‐Ting , Huang Chih‐Yang
Published: September 2014

BACKGROUND

Male Wistar rats were divided into seven groups as follows: group A, basal diet; group B, basal diet with Cholestin at 0.1667 g kg−1 body weight (BW); groups C–F, oral feeding of ethanol at 7.9 g kg−1 BW; groups D–F, Cholestin in diet at 0.1667, 0.3333 and 0.5 g kg−1 BW respectively; group G, silymarin in diet at 200 mg kg−1 BW.

RESULTS

The results showed that treatment with Cholestin for 8 weeks reduced the impact of ethanol toxicity on serum markers of liver damage: aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP). The antioxidant system was significantly enhanced: plasma and hepatic thiobarbituric acid‐reactive substance (TBARS) levels were lowered while hepatic superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH‐Px), ethanol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) activities and non‐enzymatic antioxidants (vitamin E, vitamin C and GSH) were elevated.

CONCLUSION

Cholestin shows a protective effect against hepatotoxicity indices in ethanol‐fed rats comparable to that of silymarin, as supported by the evaluation of liver histopathology. The data suggest that Cholestin exerts its hepatoprotective effect by decreasing lipid peroxidation and improving antioxidants status, thus proving itself as an effective antioxidant in ethanol‐induced oxidative damage in rats. © 2014 Society of Chemical Industry
Comparison of the effects of ionic liquid and anti‐wear additives on the tribological properties of Cr―Mo―N coatings
Authors: Feng Xin , Xia Yanqiu
Published: September 2014

Cr―Mo―N coating was prepared by magnetron sputtering, and its crystallinity and phase structure were analysed by X‐ray diffraction. The tribological properties of the coating separately lubricated with L‐P106 ionic liquid was compared with poly‐alpha‐olefin (PAO) and PAO‐containing MoDTP and ZnDTP additives with a ball‐on‐disc reciprocal friction and wear tester. It was found that the tribological properties of as‐prepared Cr―Mo―N coating vary with varying lubricant systems. Namely, the results indicated that the L‐P106 has better friction‐reducing and wear resistance properties than that of MoDTC and ZnDTP. The analyses indicated that Cr―Mo―N coatings and lubrication films can be considered as a solid–liquid duplex lubricating systems. Copyright © 2014 John Wiley & Sons, Ltd.
CAPTURING THE OPPORTUNITIES AND AVOIDING THE THREATS OF RAPID CHANGE
Authors: Kotter John P.
Published: September 2014

Companies today may require a “dual operating system,” according to Kotter. With unprecedented levels of change, complexity, and disruption, even best practices are no longer sufficient. This system blends the best of the start‐up ethos the company had in its early days with the can‐do aspects of a mature managerial and leadership system. The life cycle begins when small companies exhibit more of a nimble network structure, and then evolve into structures that exhibit more hierarchy and bureaucracy. However, the networks do not go away, and success for the future lies in tapping into the best of both of these structures.
A compactness criterion and application to the commutators associated with Schrödinger operators
Authors: Li Pengtao , Mo Yan , Zhang Chuangyuan
Published: September 2014

Let T be an integral operator. In this paper, we introduce a ‐compactness criterion of , where . As an application, we apply this criterion to deal with ‐compactness of commutators associated to Schrödinger operators with potentials in the reverse Hölder's class.