bluuebunny/crossref_metadata_2025 huggingface dataset:
Three‐dimensional numerical simulations of crustal systems undergoing orogeny and subjected to surface processes
Authors: Thieulot C. , Steer P. , Huismans R. S.
Published: December 2014

As several modeling studies indicate, the structural expression and dynamic behavior of orogenic mountain belts are dictated not only by their rheological properties or by far‐field tectonic motion, but also by the efficiency of erosion and sedimentation acting on its surface. Until recently, numerical investigations have been mainly limited to 2‐D studies because of the high computational cost required by 3‐D models. Here, we have efficiently coupled the landscape evolution model Cascade with the 3‐D thermomechanically coupled tectonics code FANTOM. Details of the coupling algorithms between both codes are given. We present results of numerical experiments designed to study the response of viscous‐plastic crustal materials subjected to convergence and to surface processes including both erosion and sedimentation. In particular, we focus on the equilibration of both the tectonic structures and on the surface morphology of the orogen. We show that increasing the efficiency of fluvial erosion increases the frontal thrust angle, which in turn decreases the width of the orogen. In addition, the maximum summit elevation of the orogen during transient evolution is significantly higher in those models showcasing surface processes than those that do not. This illustrates the strong coupling between tectonics and surface processes. We also demonstrate that an along‐strike gradient of erosion efficiency can have a major impact upon the landscape morphology and the tectonic structure and deformation of the orogen, in both the across‐strike and along‐strike directions. Overall, our results suggest that surface processes, by enhancing localization of deformation, can act as a positive forcing to topographic building.
Client Science: Bad News and the Fully Informed ADR Client
Authors: Aaron Marjorie Corman
Published: December 2014

Professor Aaron comments that this piece, excerpted from: “Bad News and the Fully Informed Client,” the first chapter of her book, Client Science, addresses the lawyer's challenge when counseling clients where “bad” news—negative, pessimistic or unwelcome developments or analysis—must be conveyed, whether or not within an ADR process. “As a mediator of civil cases, I suspect that mediation involves a higher than average percentage of cases involving ill‐counseled clients or ‘difficult clients’ who may fairly be characterized as ‘counseling‐resistant’ despite the best efforts of skilled lawyers. When the lawyer explains ‘bad news’ about case developments or likely outcomes, he risks the client's suspicion or accusation of less than zealous advocacy. While a mediator can assist with client communication when legal circumstances are grim, counsel are obligated to ensure their clients are well informed of realistic expectations when exercising autonomy and self determination.”
The influence of combined external donor and combined cocatalyst on propylene polymerization with a MgCl2‐supported Ziegler–Natta catalyst in the presence of hydrogen
Authors: Li Peiyuan , Tu Songtao , Xu Tao , Fu Zhisheng , Fan Zhiqiang
Published: December 2014

The influence of combined external donor (ED) (diphenyldimethoxysilane/dicyclopentyldimethoxysilane) and combined cocatalyst (triethylaluminum/triisobutylaluminum) on propylene polymerization with MgCl2‐supported Ziegler–Natta catalyst in the presence of hydrogen was investigated. By deconvolution analysis of the molecular weight distribution (MWD) into multiple Flory components, the influence of ED and cocatalyst on the active center distribution of the catalyst was demonstrated, and the mechanism was discussed. Using combined cocatalyst and combined donor, iPP with high molecular weight, high isotacticity index, and broad MWD can be obtained. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015, 132, 41689.
Optimization of nanofibrous silk fibroin scaffold as a delivery system for bone marrow adherent cells: in vitro and in vivo studies
Authors: Gholipourmalekabadi Mazaher , Mozafari Masoud , Bandehpour Mojgan , Salehi Mohammad , Sameni Marzieh , Caicedo Hector Hugo , Mehdipour Ahmad , Hamidabadi Hatef Ghasemi , Samadikuchaksaraei Ali , Ghanbarian Hossein
Published: December 2014

Electrospun silk fibroin nanofibrous scaffolds (ESFNSs) were successfully prepared by electrospinning of various Bombyx mori silk fibroin concentrations (10, 12, and 14% in formic acid). After characterizing the purified silk fibroin, the morphology, porosity, fibers’ diameter, and uniformity of the prepared scaffolds were examined in detail. In addition, biological responses such as effects on bone marrow cell viability, cytotoxicity, and cell adhesion were evaluated in vitro. Biocompatibility and bioactivity properties of the ESFNSs were evaluated in vitro and in vivo by cell culturing and subcutaneous implantation in rat models for 7 and 28 days, respectively. According to the obtained results, no beaded fibers were seen in any of the prepared scaffolds, whereas ESFNS‐10% provided more uniformity and porosity with nanoscaled fibers (90 ± 0.021 nm). Furthermore, the scaffolds also showed good cell adhesion and spreading (68.7 ± 11.8 and 7.6 ± 3.3 total length and width, respectively) with no detectable effect on cell viability and cytotoxicity. The in vivo biocompatibility evaluation indicated that the scaffolds did not stimulate detectable cellular inflammatory response (lymphocytes) and increased the total cell number (cellularity) in the implantation area. Furthermore, the results suggest the potential use of the prepared ESFNS‐10% bone marrow cell constructs in direct implantation for tissue engineering applications.
Determination of a novel anticancer c‐Met inhibitor LS‐177 in rat plasma and tissues with a validated UPLC‐MS/MS method: application to pharmacokinetics and tissue distribution study
Authors: Ju Ping , Liu Zhenzhen , Jiang Yu , Zhao Simin , Zhang Lunhui , Zhang Yuanyuan , Gu Liqiang , Tang Xing , Bi Kaishun , Chen Xiaohui
Published: December 2014

LS‐177 is a novel small‐molecule kinase inhibitor employed to interrupt the c‐Met signaling pathway. A rapid and sensitive ultraperformance liquid chromatography–tandem mass spectrometry (UPLC‐MS/MS) method was developed and validated for determination of LS‐177 in rat plasma and tissues. The biosamples were extracted by liquid–liquid extraction with methyl tert‐butyl ether and separated on a C18 column (50 × 4.6 mm, 2.6 µm) using a gradient elution mobile phase consisting of acetonitrile–0.1% formic acid water. Under the optimal conditions, the selectivity of the method was satisfactory with no endogenous interference. The intraday and interday precisions (relative standard deviation) were <10.5% and the accuracy (relative error) was from −12.5 to 12.5% at all quality control levels. Excellent recovery and negligible matrix effects were observed. Stability studies showed that LS‐177 was stable during the preparation and analytical processes. The UPLC‐MS/MS method was successfully applied to pharmacokinetic and tissue distribution studies. The results indicated that there was no significant drug accumulation after multiple‐dose oral administration of LS‐177. The tissue distribution study exhibited significant higher uptakes of LS‐177 in stomach, intestine, lung and liver among all of the tissues. The results in pharmacokinetics and tissue distribution may provide a meaningful basis for clinical application. Copyright © 2014 John Wiley & Sons, Ltd.
Polytraumatization in an adult national sample and its association with psychological distress and self‐esteem
Authors: Nilsson Doris , Dahlstöm Örjan , Priebe Gisela , Svedin Carl Göran
Published: December 2014

Objective

The objective of this study was to examine the prevalence of self‐reported experiences of potential childhood traumas and polytraumatization, and to find cut‐off values for different kinds of potential traumatic events in a national representative sample of adults in Sweden. In addition, to analyse the association between polytraumatization and both psychological distress and global self‐esteem.

Method

A web‐based survey ‐ containing SCL‐25 and Rosenberg Self‐Esteem Scale, and Linköping Difficult Life Events Scale ‐ Adult ‐ was sent out to a nationally reprative sample and 5062 people chose to participate in the study.

Results

Results showed that almost everyone (97%) has experienced at least one potential traumatic event and that polytraumatization (the 10% of the participants with most reported traumas) was significantly (Z = 12.57, P < 0.001, r = 0.18) associated with psychological distress and global self‐esteem. Gender differences were significant (Z = 8.44, P < 0.001, r = 0.12), in that men experience more noninterpersonal traumas but women report more symptoms. The effect sizes regarding the impact of potential trauma on self‐esteem were largest for women with experience of polytraumatization in the age group 18–25 (r = 0.48). There was almost linear increase in psychological distress and linear decrease in self‐esteem with increasing number of traumatic events experienced.

Conclusion

Experience of polytrauma can be considered an important factor to take into account in psychiatric settings as well.
An unusual case of phenotype switch between AML FAB subtypes
Authors: Das Animesh , Singh Amitabh , Gajendra Smeeta , Gupta Ritu , Sazawal Susha , Seth Rachna
Published: December 2014

Key Clinical Message

Phenotypic switch between any leukemia subtypes is of concern to a treating physician and more so, in acute myelocytic leukemia (AML) as the mechanisms for switch and subsequent chemotherapy regimen to be used remain unclear. AML‐non‐M3 from AML‐M3 subtype needs special mention as this has been unheard off.
Fully Automated Reactor System for Continuous Characterization of (Bio)catalysts
Authors: Lyagin Evgenij , Drews Anja , Kraume Matthias
Published: December 2014

The existing screening and characterization systems for biocatalysts operate in batch mode, which could make catalyst selection and process development inaccurate when continuous operation mode is required in industry. A significant improvement of an innovative screening system based on miniaturized multiple membrane reactors formerly presented by the author is outlined, which enables continuous feeding of substrates and continuous removal of products. Although the presented screening system was originally designed for homogeneous enzymatic reactions, it can be used without further modifications for continuous catalysis with polymer‐bound chemical catalysts or for quasi‐homogeneous systems like reverse micelles.
Gaussian Beam First‐Arrival Waveform Inversion Based on Born Wavepath
Authors: Yu‐Zhu LIU , Chun XIE , Ji‐Zhong YANG
Published: December 2014

We propose a new waveform inversion method to improve the accuracy of the near surface velocity structure. Only the first‐arrival waveform is used in this method to decrease the nonlinearity between wavefield and model parameters and the dependency of waveform inversion on the starting model. To increase the computational efficiency of forward calculation, we use Gaussian Beam (GB) method to calculate the Green function and the first‐arrival wavefield. To avoid the storage of the huge Fréchet matrix, based on Born wavepath, we propose the calculation of the direction and step length in waveform inversion using matrix decomposition, accomplished by accumulation. We then apply this new first‐arrival waveform inversion method on a numerical experiment. The comparisons between this method and traditional acoustic full waveform inversion (FWI) and ray‐based first‐arrival traveltime tomography (RFTT) show that it can obtain a result a little worse than FWI while much better than traditional RFTT, while the computational efficiency is almost the same as RFTT. Meanwhile, the dependence of this method on the starting model is much weaker than FWI.
Observation of Upper Atmospheric Temperature by Kunming All‐Sky Meteor Radar
Authors: Wen YI , Jin‐Song CHEN , Chun‐Bo MA , Na LI , Zhen‐Wei ZHAO
Published: December 2014

Using the data collected by the all‐sky meteor radar with two different operating frequencies at the Kunming station (25.6°N, 103.8°E) during the special joint observation experiment in 2011. Based on the method improved by Hocking, we determined the mesopause above the height of peak meteor activity, and then used different temperature gradients to inversion of atmospheric temperature at 88 km and 85 km over Kunming. Comparison with the Aura satellite temperature data shows that two separate meteor radars can measure correct atmospheric temperature at the height of peak meteor activity, however the correlation between temperature determined by the meteor radar using temperature gradient model and satellite temperature is not well. While the temperature determined by meteor radar using satellite temperature gradients have good correlation with satellite temperature. It is concluded that the accurate temperature gradient is very important in the Hocking's method.
Reducing the effects of the noise uncertainty in energy detectors for cognitive radio networks
Authors: Martínez Daniela M. , Andrade Ángel G.
Published: December 2014

Because of its ease of implementation and minimum requirements about the primary signals' information, energy detection is broadly considered for signal detection in spectrum sensing algorithms. However, the noise uncertainty phenomenon, caused by the random variations in the noise power, degrades the performance of an energy detector, particularly when the signal‐to‐noise ratio (SNR) is low. In this work, we propose to reduce the negative effects of the noise uncertainty in the performance of an energy detector by dynamically adapting its detection threshold to the noise conditions experienced at each sensing epoch. The noise power is estimated from the received signal samples using an algorithm based on a high‐pass filters bank and median filtering. With our proposal, it is possible to maintain a constant and low false alarm rate in the presence of noise uncertainty, without increasing the probability of misdetection, even in the low SNR regime, and without increasing the number of samples considered for spectrum sensing. Copyright © 2014 John Wiley & Sons, Ltd.
Pyroptosis of resident macrophages differentially orchestrates inflammatory responses to Staphylococcus aureus in resistant and susceptible mice
Authors: Accarias Solène , Lugo‐Villarino Geanncarlo , Foucras Gilles , Neyrolles Olivier , Boullier Séverine , Tabouret Guillaume
Published: December 2014

The relationship between Staphylococcus aureus and innate immunity is highly complex and requires further investigation to be deciphered. i.p. challenge of C57BL/6 and DBA/2 mice, resistant and susceptible to the infection, respectively, resulted in different patterns of cytokine production and neutrophil recruitment. Staphylococcus aureus infection induced macrophage pyroptosis, an inflammasome‐dependent cell death program, whose rates significantly differed between C57BL/6 and DBA/2 mice. Fast rate pyroptosis of C57BL/6 macrophages released high levels of IL‐1β but limited the synthesis of other cytokines such as TNF‐α, IL‐6, CXCL1, and CXCL2. Conversely, the extended survival of DBA/2 macrophages allowed substantial production of these NF‐κB‐related cytokines. Phenotyping of resting macrophages in different mouse strains revealed differential predisposition toward specific macrophage phenotypes that modulate S. aureus‐mediated inflammasome activation. Treatment of DBA/2 susceptible mice with inflammasome inducers (i.e. nigericin and ATP) artificially increased pyroptosis and lowered the levels of NF‐κB‐related inflammatory cytokines, but restored IL‐1β to levels similar to those in C57BL/6 mice. Collectively, this study promotes the concept that, in association with host genetics, the basal phenotype of resident macrophages influences the early inflammatory response and possibly participates in S. aureus infection outcome via the inflammasome pathway and subsequent pyroptosis.
Structural basis for ineffective T‐cell responses to MHC anchor residue‐improved “heteroclitic” peptides
Authors: Madura Florian , Rizkallah Pierre J. , Holland Christopher J. , Fuller Anna , Bulek Anna , Godkin Andrew J. , Schauenburg Andrea J. , Cole David K. , Sewell Andrew K.
Published: December 2014

MHC anchor residue‐modified “heteroclitic” peptides have been used in many cancer vaccine trials and often induce greater immune responses than the wild‐type peptide. The best‐studied system to date is the decamer MART‐1/Melan‐A26–35 peptide, EAAGIGILTV, where the natural alanine at position 2 has been modified to leucine to improve human leukocyte antigen (HLA)‐A*0201 anchoring. The resulting ELAGIGILTV peptide has been used in many studies. We recently showed that T cells primed with the ELAGIGILTV peptide can fail to recognize the natural tumor‐expressed peptide efficiently, thereby providing a potential molecular reason for why clinical trials of this peptide have been unsuccessful. Here, we solved the structure of a TCR in complex with HLA‐A*0201‐EAAGIGILTV peptide and compared it with its heteroclitic counterpart , HLA‐A*0201‐ELAGIGILTV. The data demonstrate that a suboptimal anchor residue at position 2 enables the TCR to “pull” the peptide away from the MHC binding groove, facilitating extra contacts with both the peptide and MHC surface. These data explain how a TCR can distinguish between two epitopes that differ by only a single MHC anchor residue and demonstrate how weak MHC anchoring can enable an induced‐fit interaction with the TCR. Our findings constitute a novel demonstration of the extreme sensitivity of the TCR to minor alterations in peptide conformation.
Silence STAT3 in the procancer niche…and activate CD8+ T cells to kill premetastatic myeloid intruders
Authors: Auphan‐Anezin Nathalie , Schmitt‐Verhulst Anne‐Marie
Published: December 2014

Several recent studies have implicated myeloid cells in providing a microenvironment that promotes tumor cell survival and metastasis, therefore preparing a “premetastatic niche” for cancer progression. In this issue of the European Journal of Immunology, Zhang et al. [Eur. J. Immunol. 2015. 45: 71–81] address the regulation of immune cells in premetastatic lymph nodes in experimental mouse models. The authors show that signal transducer and activator of transcription 3 (STAT3) ablation in murine myeloid cells, which renders the premetastatic niche less receptive to metastasis by B16 melanoma cells, also leads to local activation in the niche of CD8+ T cells with increased expression of IFN‐γ and granzyme B. Data further suggest that STAT3 activation in the myeloid population leads to poor tumor antigen presenting capacity as well as resistance to CD8+ T‐cell killing. Based on these studies in mice and observations in human cancer patients, the authors propose treatments designed to regulate STAT3 activation, which are correlated with increased cytolytic activity of CD8+ T cells in mouse models.
Formation and Stability of Gaseous Ternary Oxides of Group 14–16 Elements and Related Oxides of Group 15 Elements: Mass Spectrometric and Quantum Chemical Study
Authors: Kunkel Katerina , Milke Edgar , Binnewies Michael
Published: December 2014

The formation of four hitherto unknown lead tellurium oxides – PbTeO3, PbTe2O5, Pb2TeO4 and Pb2Te2O6 – was observed in the gas phase by means of a mass‐spectrometric Knudsen‐cell method. Other ternary oxides of group 14–16 elements were not observed in the gas phase. The enthalpies of formation for these oxides were obtained experimentally by means of a mass‐spectrometric Knudsen‐cell method and confirmed theoretically by using quantum chemical (QC) calculations. Appearance potential measurements were conducted for PbTeO3 and Pb2TeO4. The structures of the ternary oxides that represent the minima on the potential‐energy surfaces were found by using QC calculations. The behaviour of the related compounds PbTeO3, X2O3, Pb2Te2O6 and X4O6 in the gas phase has been discussed (for which X = P, As, Sb, Bi).
Preparation of Pillar[5]arene‐Based [2]Rotaxanes from Acyl Chlorides and Amines
Authors: Milev Radian , Lopez‐Pacheco Alberto , Nierengarten Iwona , Trinh Thi Minh Nguyet , Holler Michel , Deschenaux Robert , Nierengarten Jean‐François
Published: December 2014

Pillar[5]arene‐based [2]rotaxanes have been prepared from the reactions of diacyl chloride reagents with various amine stoppers. The yields of the [2]rotaxanes are sensitive to the reaction conditions (solvent and stoichiometry) as well as to structural and electronic factors. In particular, the nature of the starting amine reagent has a dramatic influence on the yields of [2]rotaxanes; thus, the reaction outcome is not simply related to the binding constant of the diacyl chloride reagent with the pillar[5]arene. Indeed, the differences in the yields must be related to the different affinities for the various monoacylated intermediates. The yields of the [2]rotaxanes are also influenced by several structural factors such as the chain length of the diacyl chloride reagent and the size of the peripheral substituents of the pillar[5]arene building block. Finally, the preparation of [2]rotaxanes from alkyldiamine reagents and acyl chloride stoppers has also been investigated.
CD11c‐positive cells from brain, spleen, lung, and liver exhibit site‐specific immune phenotypes and plastically adapt to new environments
Authors: Immig Kerstin , Gericke Martin , Menzel Franziska , Merz Felicitas , Krueger Martin , Schiefenhövel Fridtjof , Lösche Andreas , Jäger Kathrin , Hanisch Uwe‐Karsten , Biber Knut , Bechmann Ingo
Published: December 2014

The brain's immune privilege has been also attributed to the lack of dendritic cells (DC) within its parenchyma and the adjacent meninges, an assumption, which implies maintenance of antigens rather than their presentation in lymphoid organs. Using mice transcribing the green fluorescent protein under the promoter of the DC marker CD11c (itgax), we identified a juxtavascular population of cells expressing this DC marker and demonstrated their origin from bone marrow and local microglia. We now phenotypically compared this population with CD11c/CD45 double‐positive cells from lung, liver, and spleen in healthy mice using seven‐color flow cytometry. We identified unique, site‐specific expression patterns of F4/80, CD80, CD86, CX3CR1, CCR2, FLT3, CD103, and MHC‐II. Furthermore, we observed the two known CD45‐positive populations (CD45high and CD45int) in the brain, whereas liver, lung, and spleen exhibited a homogeneous CD45high population. CD11c‐positive microglia lacked MHC‐II expression and CD45high/CD11c‐positive cells from the brain have a lower percentage of MHC‐II‐positive cells. To test whether phenotypical differences are fixed by origin or specifically develop due to environmental factors, we transplanted brain and spleen mononuclear cells on organotypic slice cultures from brain (OHSC) and spleen (OSSC). We demonstrate that adaption and ramification of MHC‐II‐positive splenocytes is paralleled by down‐regulation of MHC‐II, whereas brain‐derived mononuclear cells neither ramified nor up‐regulated MHC‐II in OSSCs. Thus, brain‐derived mononuclear cells maintain their MHC‐II‐negative phenotype within the environment of an immune organ. Intraparenchymal CD11c‐positive cells share immunophenotypical characteristics of DCs from other organs but remain unique for their low MHC‐II expression. GLIA 2015;63:611–625
Generation of MHC class I diversity in primary tumors and selection of the malignant phenotype
Authors: Garrido Federico , Romero Irene , Aptsiauri Natalia , Garcia‐Lora Angel M.
Published: December 2014

Intratumor heterogeneity among cancer cells is promoted by reversible or irreversible genetic alterations and by different microenvironmental factors. There is considerable experimental evidence of the presence of a variety of malignant cell clones with a wide diversity of major histocompatibility class I (MHC‐I) expression during early stages of tumor development. This variety of MHC‐I phenotypes may define the evolution of a particular tumor. Loss of MHC‐I molecules frequently results in immune escape of MHC‐negative or ‐deficient tumor cells from the host T cell‐mediated immune response. We review here the results obtained by our group and other researchers in animal models and humans, showing how MHC‐I intratumor heterogeneity may affect local oncogenicity and metastatic progression. In particular, we summarize the data obtained in an experimental mouse cancer model of a methylcholanthrene‐induced fibrosarcoma (GR9), in which isolated clones with different MHC‐I expression patterns demonstrated distinct local tumor growth rates and metastatic capacities. The observed “explosion of diversity” of MHC‐I phenotypes in primary tumor clones and the molecular mechanism (“hard”/irreversible or “soft”/reversible) responsible for a given MHC‐I alteration might determine not only the metastatic capacity of the cells but also their response to immunotherapy. We also illustrate the generation of further MHC heterogeneity during metastatic colonization and discuss different strategies to favor tumor rejection by counteracting MHC‐I loss. Finally, we highlight the role of MHC‐I genes in tumor dormancy and cell cycle control.
Interleukin‐34 promotes tumor progression and metastatic process in osteosarcoma through induction of angiogenesis and macrophage recruitment
Authors: Ségaliny Aude I. , Mohamadi Amel , Dizier Blandine , Lokajczyk Anna , Brion Régis , Lanel Rachel , Amiaud Jérôme , Charrier Céline , Boisson‐Vidal Catherine , Heymann Dominique
Published: December 2014

Interleukin‐34 (IL‐34) was recently characterized as the M‐CSF “twin” cytokine, regulating the proliferation/differentiation/survival of myeloid cells. The implication of M‐CSF in oncology was initially suspected by the reduced metastatic dissemination in knock‐out mice, due to angiogenesis impairment. Based on this observation, our work studied the involvement of IL‐34 in the pathogenesis of osteosarcoma. The in vivo effects of IL‐34 were assessed on tissue vasculature and macrophage infiltration in a murine preclinical model based on a paratibial inoculation of human osteosarcoma cells overexpressing or not IL‐34 or M‐CSF. In vitro investigations using endothelial cell precursors and mature HUVEC cells were performed to analyse the involvement of IL‐34 in angiogenesis and myeloid cell adhesion. The data revealed that IL‐34 overexpression was associated with the progression of osteosarcoma (tumor growth, lung metastases) and an increase of neo‐angiogenesis. In vitro analyses demonstrated that IL‐34 stimulated endothelial cell proliferation and vascular cord formation. Pre‐treatment of endothelial cells by chondroitinases/heparinases reduced the formation of vascular tubes and abolished the associated cell signalling. In addition, IL‐34 increased the in vivo recruitment of M2 tumor‐associated macrophages into the tumor tissue. IL‐34 increased in vitro monocyte/CD34+ cell adhesion to activated HUVEC monolayers under physiological shear stress conditions. This work also demonstrates that IL‐34 is expressed by osteosarcoma cells, is regulated by TNF‐α, IL‐1β, and contributes to osteosarcoma growth by increasing the neo‐angiogenesis and the recruitment of M2 macrophages. By promoting new vessel formation and extravasation of immune cells, IL‐34 may play a key role in tumor development and inflammatory diseases.
Antibody targeting of HER2/HER3 signaling overcomes heregulin‐induced resistance to PI3K inhibition in prostate cancer
Authors: Poovassery Jayakumar S. , Kang Jeffrey C. , Kim Dongyoung , Ober Raimund J. , Ward E. Sally
Published: December 2014

Dysregulated expression and/or mutations of the various components of the phosphoinositide 3‐kinase (PI3K)/Akt pathway occur with high frequency in prostate cancer and are associated with the development and progression of castration resistant tumors. However, small molecule kinase inhibitors that target this signaling pathway have limited efficacy in inhibiting tumor growth, primarily due to compensatory survival signals through receptor tyrosine kinases (RTKs). Although members of the epidermal growth factor receptor (EGFR), or HER, family of RTKs are strongly implicated in the development and progression of prostate cancer, targeting individual members of this family such as EGFR or HER2 has resulted in limited success in clinical trials. Multiple studies indicate a critical role for HER3 in the development of resistance against both HER‐targeted therapies and PI3K/Akt pathway inhibitors. In this study, we found that the growth inhibitory effect of GDC‐0941, a class I PI3K inhibitor, is markedly reduced in the presence of heregulin. Interestingly, this effect is more pronounced in cells lacking phosphatase and tensin homolog function. Heregulin‐mediated resistance to GDC‐0941 is associated with reactivation of Akt downstream of HER3 phosphorylation. Importantly, combined blockade of HER2 and HER3 signaling by an anti‐HER2/HER3 bispecific antibody or a mixture of anti‐HER2 and anti‐HER3 antibodies restores sensitivity to GDC‐0941 in heregulin‐treated androgen‐dependent and ‐independent prostate cancer cells. These studies indicate that the combination of PI3K inhibitors with HER2/HER3 targeting antibodies may constitute a promising therapeutic strategy for prostate cancer.
Direct determination of methyl parathion insecticide in rice samples by headspace solid‐phase microextraction–gas chromatography–mass spectrometry
Authors: da Silva Darlan Ferreira , Paiva Silva Francisco Eduardo , Silva Fernanda Gabrielle S , Nunes Gilvanda Silva , Badea Mihaela
Published: December 2014

BACKGROUND

The organophosphorus insecticides, especially those based on methyl parathion as active principle, have been used extensively in the protection of rice in Maranhão State, in the north‐east of Brazil. This paper describes the optimisation of a solid‐phase microextraction (SPME) procedure in confined atmosphere (headspace, HS) for the determination of methyl parathion in rice organic samples by gas chromatography with mass spectrometry detection (GC/MS).

RESULTS

The proposed HS‐SPME‐GC/MS method has been shown to be appropriate for direct analysis of the insecticide in polished rice, with satisfactory results for the following parameters: linearity (correlation coefficient 0.9985), sensitivity (LOD and LOQ of 0.026 and 0.078 µg kg−1 respectively), precision (coefficients of variation between 6.1 and 22.4%) and accuracy (recoveries varying from 73.2 to 90.0%). Although the efficiency of the proposed GC/MS does not differ statistically (P < 0.05) from the conventional GC/NPD method, given its low cost, speed and also the fact that a minimum volume of toxic effluent is generated, this method can be considered an on‐line procedure based on green chemistry.

CONCLUSIONS

Thus, the analytical methodology satisfies the minimum requirements for control of residues of such insecticides in rice samples destined for human consumption. © 2014 Society of Chemical Industry
Randomization inference for treatment effects on a binary outcome
Authors: Rigdon Joseph , Hudgens Michael G.
Published: December 2014

Two methods are developed for constructing randomization‐based confidence sets for the average effect of a treatment on a binary outcome. The methods are nonparametric and require no assumptions about random sampling from a larger population. Both of the resulting 1 −αconfidence sets are exact in the sense that the probability of containing the true treatment effect is at least 1 −α. Both types of confidence sets are also guaranteed to have width no greater than one. In contrast, a previously proposed asymptotic confidence interval is not exact and may have width greater than 1. The first approach combines Bonferroni‐adjusted prediction sets for the attributable effects in the treated and untreated. The second method entails inverting a permutation test. Simulations are presented comparing the two randomization‐based confidence sets with the asymptotic interval as well as the standard Wald confidence interval and a commonly used exact interval for the difference in binomial proportions. Results show for small to moderate sample sizes that the permutation confidence set attains the narrowest width on average among the methods that maintain nominal coverage. Extensions that allow for stratifying on categorical baseline covariates are also discussed. Copyright © 2014 John Wiley & Sons, Ltd.
Structural and functional properties of endosperm starch and flour from dicotyledon Mirabilis jalapa
Authors: Wang Ping , Huang Jun , Zhao Lingxiao , Chen Yifang , Wei Cunxu
Published: December 2014

The large endosperm of dicotyledon Mirabilis jalapa may have food and non‐food industrial applications because of its high starch content. In this study, the structural and functional properties of endosperm starch and flour from M. jalapa were investigated. Each seed (about 170.8 mg fresh weight) contained approximately 37.3 mg of dry endosperm. The endosperm contained about 80.1% starch, 1.5% soluble sugar, and 2.3% protein. Starch granules were small (about 1.5 µm) with a regular spherical shape. The starch contained about 56.5% short branch‐chain of amylopectin, 21.3% long branch‐chain of amylopectin, and 22.2% amylose. The starch and flour had CA‐type crystallinity, while the swelling power and water solubility of starch were 15.8 g/g and 17.1%, respectively. The starch had lower gelatinization temperature and higher pasting viscosity than flour. No peak and hot viscosity was observed in pasting profiles of starch and flour. The flour had higher resistance to acid and amylase hydrolysis than starch. Native, gelatinized and retrograded starches had about 16.3%, 86.6%, and 76.6% of rapidly digestible starch, and 46.5%, 2.4%, and 11.8% of resistant starch, respectively. These results were compared with those obtained from monocotyledon rice endosperm starch and flour.
PBI-05204, a supercritical CO2 extract of Nerium oleander, inhibits growth of human pancreatic cancer via targeting the PI3K/mTOR pathway
Authors: Pan Yong , Rhea Patrea , Tan Lin , Cartwright Carrie , Lee Ho-Jeong , Ravoori Murali K. , Addington Crandell , Gagea Mihai , Kundra Vikas , Kim Sun-Jin , Newman Robert A. , Yang Peiying
Published: December 2014

Introduction Oleandrin, a cardiac glycoside, exerts strong anti-proliferative activity against various human malignancies in in vitro cells. Here, we report the antitumor efficacy of PBI-05204, a supercritical C02 extract of Nerium oleander containing oleandrin, in a human pancreatic cancer Panc-1 orthotopic model. Results While all the control mice exhibited tumors by the end of treatment, only 2 of 8 mice (25 %) treated for 6 weeks with PBI-05204 (40 mg/kg) showed dissectible tumor at the end of the treatment period. The average tumor weight (222.9 ± 116.9 mg) in mice treated with PBI-05204 (20 mg/kg) was significantly reduced from that in controls (920.0 ± 430.0 mg) (p < 0.05). Histopathologic examination of serial sections from each pancreas with no dissectible tumor in the PBI-05204 (40 mg/kg) treated group showed that the pancreatic tissues of 5/6 mice were normal while the remaining mouse had a tumor the largest diameter of which was less than 2.3 mm. In contrast, while gemcitabine alone did not significantly reduce tumor growth, PBI-05204 markedly enhanced the antitumor efficacy of gemcitabine in this particular model. Ki-67 staining was reduced in pancreatic tumors from mice treated with PBI-05204 (20 mg/kg) compared to that of control, suggesting that PBI-05204 inhibited the proliferation of the Panc-1 tumor cells. PBI-05204 suppressed expression of pAkt, pS6, and p4EPB1 in a concentration-dependent manner in both Panc-1 tumor tissues and human pancreatic cancer cell lines, implying that this novel botanical drug exerts its potent antitumor activity, at least in part, through down-regulation of PI3k/Akt and mTOR pathways.
A Tear in the Fabric: the James Bulger Murder and New Theatre Writing in the 'Nineties
Authors: Ravenhill Mark
Published: December 2014

It is not yet ten years since Mark Ravenhill's Shopping and Fucking reached the stage of the Royal Court, during its West End exile in 1996; yet the play has already become, with Sarah Kane's Blasted, identified as central to the emergence of so-called ‘in-yer-face’ theatre. While Mark Ravenhill recognized the influence of such writers as Martin Crimp and David Mamet, it was only recently, during a discussion over coffee about a possible screenplay, that he began to consider the effects of both private and public events of 1993 upon his emergence as a writer – the death of a partner, and the infamous murder of a child by other children. In the following article he identifies recurrent concerns in his first three plays which he now sees as a working-out of his responses to a year which was crucial not only to his own personal narrative, but to others for whom the James Bulger murder epitomized all the worst aspects of a society that the Thatcherites claimed no longer to exist. Among Mark Ravenhill's more recent plays have been Mother Clap's Molly House, which transferred from the National Theatre to the Aldwych in 2002, and Totally Over You, written for the 2003 Shell Connections youth theatre season at the National. This article was first presented as the Marjorie Francis Lecture at Goldsmiths' College, University of London, on 5 May 2004.
Morita cohomology
Authors: HOLSTEIN JULIAN V. S.
Published: December 2014

We consider two categorifications of the cohomology of a topological spaceXby taking coefficients in the category of differential graded categories. We consider both derived global sections of a constant presheaf and singular cohomology and find the resulting dg-categories are quasi-equivalent and moreover quasi-equivalent to representations in perfect complexes of chains on the loop space ofX.
Healthy food access for urban food desert residents: examination of the food environment, food purchasing practices, diet and BMI
Authors: Dubowitz Tamara , Zenk Shannon N , Ghosh-Dastidar Bonnie , Cohen Deborah A , Beckman Robin , Hunter Gerald , Steiner Elizabeth D , Collins Rebecca L
Published: December 2014

Objective

To provide a richer understanding of food access and purchasing practices among US urban food desert residents and their association with diet and BMI.

Design

Data on food purchasing practices, dietary intake, height and weight from the primary food shopper in randomly selected households (n 1372) were collected. Audits of all neighbourhood food stores (n 24) and the most-frequented stores outside the neighbourhood (n 16) were conducted. Aspects of food access and purchasing practices and relationships among them were examined and tests of their associations with dietary quality and BMI were conducted.

Setting

Two low-income, predominantly African-American neighbourhoods with limited access to healthy food in Pittsburgh, PA, USA.

Subjects

Household food shoppers.

Results

Only one neighbourhood outlet sold fresh produce; nearly all respondents did major food shopping outside the neighbourhood. Although the nearest full-service supermarket was an average of 2·6 km from their home, respondents shopped an average of 6·0 km from home. The average trip was by car, took approximately 2 h for the round trip, and occurred two to four times per month. Respondents spent approximately $US 37 per person per week on food. Those who made longer trips had access to cars, shopped less often and spent less money per person. Those who travelled further when they shopped had higher BMI, but most residents already shopped where healthy foods were available, and physical distance from full-service supermarkets was unrelated to weight or dietary quality.

Conclusions

Improved access to healthy foods is the target of current policies meant to improve health. However, distance to the closest supermarket might not be as important as previously thought, and thus policy and interventions that focus merely on improving access may not be effective.
Redox control of glutamine utilization in cancer
Authors: Alberghina L , Gaglio D
Published: December 2014

Glutamine utilization promotes enhanced growth of cancer cells. We propose a new concept map of cancer metabolism in which mitochondrial NADH and NADPH, in the presence of a dysfunctional electron transfer chain, promote reductive carboxylation from glutamine. We also discuss why nicotinamide nucleotide transhydrogenase (NNT) is required in vivo for glutamine utilization by reductive carboxylation. Moreover, NADPH, generated by both the pentose phosphate pathway and the cancer-specific serine glycolytic diversion, appears to sustain glutamine utilization for amino-acid synthesis, lipid synthesis, and for ROS quenching. The fact that the supply of NAD+ precursors reduces tumor aggressiveness suggests experimental approaches to clarify the role of the NADH-driven redox network in cancer.
JWA reverses cisplatin resistance via the CK2—XRCC1 pathway in human gastric cancer cells
Authors: Xu W , Chen Q , Wang Q , Sun Y , Wang S , Li A , Xu S , Røe O D , Wang M , Zhang R , Yang L , Zhou J
Published: December 2014

Gastric cancer is the third most common malignancy in China, with a median 5-year survival of only 20%. Cisplatin has been used in first-line cancer treatment for several types of cancer including gastric cancer. However, patients are often primary resistant or develop acquired resistance resulting in relapse of the cancer and reduced survival. Recently, we demonstrated that the reduced expression of base excision repair protein XRCC1 and its upstream regulator JWA in gastric cancerous tissues correlated with a significant survival benefit of adjuvant first-line platinum-based chemotherapy as well as XRCC1 playing an important role in the DNA repair of cisplatin-resistant gastric cancer cells. In the present study, we demonstrated the role of JWA in cisplatin-induced DNA lesions and aquired cisplatin resistance in five cell-culture models: gastric epithelial cells GES-1, cisplatin-sensitive gastric cancer cell lines BGC823 and SGC7901, and the cisplatin-resistant gastric cancer cell lines BGC823/DDP and SGC7901/DDP. Our results indicated that JWA is required for DNA repair following cisplatin-induced double-strand breaks (DSBs) via XRCC1 in normal gastric epithelial cells. However, in gastric cancer cells, JWA enhanced cisplatin-induced cell death through regulation of DNA damage-induced apoptosis. The protein expression of JWA was significantly decreased in cisplatin-resistant cells and contributed to cisplatin resistance. Interestingly, as JWA upregulated XRCC1 expression in normal cells, JWA downregulated XRCC1 expression through promoting the degradation of XRCC1 in cisplatin-resistant gastric cancer cells. Furthermore, the negative regulation of JWA to XRCC1 was blocked due to the mutation of 518S/519T/523T residues of XRCC1, and indicating that the CK2 activated 518S/519T/523T phosphorylation is a key point in the regulation of JWA to XRCC1. In conclusion, we report for the first time that JWA regulated cisplatin-induced DNA damage and apoptosis through the CK2—P-XRCC1—XRCC1 pathway, indicating a putative drug target for reversing cisplatin resistance in gastric cancer.
A sensitive one-step method for quantitative detection of α-amylase in serum and urine using a personal glucose meter
Authors: Wang Qing , Wang Hui , Yang Xiaohai , Wang Kemin , Liu Rongjuan , Li Qing , Ou Jinqing
Published: December 2014

A one-step assay for direct determination of α-amylase activity in serum and urine was developed using a portable personal glucose meter.
Regioselective [2+2] and [4+2] cycloaddition reactivity in an asymmetric niobium(bisimido) moiety towards unsaturated organic molecules
Authors: Obenhuber A. H. , Gianetti T. L. , Bergman R. G. , Arnold J.
Published: December 2014

The asymmetric bis-imido structure and the lability of the diethyl ether linkage in complex 1 provide a niobium complex that undergoes regioselective [4+2] cycloaddition reactions with an α,β-unsaturated ketone and cycloaddition reactions that involve bond formation to the MAD ligand (MAD = monoazabutadiene).
Selective disruption of each part of Janus molecular assemblies by lateral diffusion of stimuli-responsive amphiphilic peptides
Authors: Ueda Motoki , Uesaka Akihiro , Kimura Shunsaku
Published: December 2014

Stimuli-responsive Janus-type assemblies with a round-bottom flask shape are prepared from amphiphilic helical peptides using the patchwork self-assembly technique.
A luminescent metal–organic framework constructed using a tetraphenylethene-based ligand for sensing volatile organic compounds
Authors: Liu Xun-Gao , Wang Hui , Chen Bin , Zou Yang , Gu Zhi-Guo , Zhao Zujin , Shen Liang
Published: December 2014

A tetraphenylethene-based porous metal–organic framework with 1D rhombus channels and strong fluorescence is prepared and applied to detect volatile organic compounds.
Inhibition of Alzheimer's amyloid-β peptide aggregation and its disruption by a conformationally restricted α/β hybrid peptide
Authors: Paul Ashim , Nadimpally Krishna Chaitanya , Mondal Tanmay , Thalluri Kishore , Mandal Bhubaneswar
Published: December 2014

A novel class of anthranilic acid containing a conformationally restricted β-sheet breaker α/β-hybrid peptide efficiently disrupts preformed fibrillar aggregates of Aβ1–40in vitro.
Photoswitching of triplet–triplet annihilation upconversion showing large emission shifts using a photochromic fluorescent dithienylethene-Bodipy triad as a triplet acceptor/emitter
Authors: Xu Kejing , Zhao Jianzhang , Cui Xiaoneng , Ma Jie
Published: December 2014

A dithienylethene-Bodipy triad was used as a photoswitchable triplet acceptor/emitter for photoswitching of triplet–triplet annihilation upconversion with large emission wavelength changes.
Solution and solid-phase halogen and C–H hydrogen bonding to perrhenate
Authors: Massena Casey J. , Riel Asia Marie S. , Neuhaus George F. , Decato Daniel A. , Berryman Orion B.
Published: December 2014

In the presence of perrhenate, two receptor molecules form unique multidentate halogen and hydrogen bonds in solution and solid phases.
Encapsulation of secondary and tertiary ammonium salts by resorcinarenes and pyrogallarenes: the effect of size and charge concentration
Authors: Beyeh N. K. , Pan F. , Valkonen A. , Rissanen K.
Published: December 2014

Multiple weak interactions are manifested in the complexation of different categories of secondary and tertiary alkyl ammonium salts with resorcinarenes and pyrogallarene leading to open inclusion and dimeric capsular assemblies with varying binding affinities, and analyzed in solid, liquid and gas phases.
Energetic contributions of residues to the formation of early amyloid-β oligomers
Authors: Pouplana R. , Campanera J. M.
Published: December 2014

The hydrophobic interaction between the C-terminal region (31–35) and the central hydrophobic region (17–20) in a pseudo-perpendicular orientation favours the intermonomeric stabilisation of Aβ10–35oligomers.
Strain effects on oxygen migration in perovskites
Authors: Mayeshiba Tam , Morgan Dane
Published: December 2014

Computational results show that a 2% biaxial tensile strain may increase oxygen ion conduction, both in- and out-of-plane, by up to approximately three orders of magnitude at 300 K in the most strain-sensitive LaBO3 perovskites, where B = [Sc, Ti, V, Cr, Mn, Fe, Co, Ni, Ga].
Overcoming crystallographically imposed geometrical restrictions on the valence state of Eu in CaGdAlO4: realization of white light emission from singly-doped Eu phosphors
Authors: Zhang Yang , Liu Xiaoming , Li Xuejiao , Li Kai , Lian Hongzhou , Shang Mengmeng , Lin Jun
Published: December 2014

The crystallographically imposed geometrical restrictions on the valence state of Eu in CaGdAlO4 has been overcome by the replacement of Al3+–Gd3+ with Si4+–Ca2+.
Pitfalls and progress: a perspective on achieving sustainable sanitation for all
Authors: Templeton Michael R.
Published: December 2014

This article provides a perspective on the reasons behind why we have not yet achieved sustainable sanitation for all, i.e. universal access to some form of improved toilet and sludge management services, and presents research needs and strategies for moving closer to this goal.