bluuebunny/crossref_metadata_2025 huggingface dataset:
L’art de juger : sources et méthodologie. Ce que révèle l’œuvre du juge Louis LeBel
Authors: Rousseau Houle Thérèse
Published: June 2016

L’art de juger, tout comme ses notions connexes, l’acte de juger ou la faculté de juger, sont au coeur de la pensée juridique dans les traditions tant civilistes que de common law. Il appartient aux juges de réinterpréter l’héritage juridique en confrontant celui-ci aux valeurs et aux principes qui fondent la justice dans la société contemporaine. L’acte de juger devient un acte de culture, une façon de rappeler ou de dénoncer les consensus sociaux afin d’ajuster le droit à la réalité sociale. Par-delà les frontières et les ordres de juridiction s’instaure un dialogue incitant les juges à mettre en oeuvre une sorte de droit mondialisé marqué par la rationalité économique et le respect du principe de la dignité de l’être humain. L’acte de juger, surtout depuis l’avènement des chartes, est devenu un acte politique. Cela exige des juges une ouverture aux nouvelles perspectives sociales, philosophiques et politiques et l’adoption de nouvelles méthodologies à caractère plus sociologique et plus scientifique. Une analyse, sans doute imparfaite et incomplète, de quelques opinions du juge Louis LeBel pendant sa carrière à la Cour suprême du Canada, suggère le regroupement de ses choix méthodologiques sous trois titres principaux : le dialogue des cultures, la rhétorique des droits constitutionnels et l’avenir du droit. La protection des droits collectifs et la recherche d’une nécessaire réconciliation des valeurs communes fondamentales sont, pour le juge LeBel, des éléments essentiels à la survie d’une démocratie fondée sur la primauté du droit.
Portes et fenêtres – Louis LeBel et l’approche québécoise relative à l’interprétation du droit interne à la lumière du droit international
Authors: Van Ert Gib
Published: June 2016

L’orthodoxie anglaise quant à la réception en droit interne des obligations conventionnelles internationales veut que celles-ci ne puissent avoir aucun effet sans mise en oeuvre par voie législative. Dans ce qui suit, l’auteur soutient que l’orthodoxie simplifie à outrance et que certains jugements des juges québécois de la Cour suprême du Canada ont, à juste titre, éloigné la position canadienne de cette orthodoxie, mais sans l’abandonner complètement.
Nerve growth factor receptor negates the tumor suppressor p53 as a feedback regulator
Authors: Zhou Xiang , Hao Qian , Liao Peng , Luo Shiwen , Zhang Minhong , Hu Guohui , Liu Hongbing , Zhang Yiwei , Cao Bo , Baddoo Melody , Flemington Erik K , Zeng Shelya X , Lu Hua
Published: June 2016

Cancer develops and progresses often by inactivating p53. Here, we unveil nerve growth factor receptor (NGFR, p75NTR or CD271) as a novel p53 inactivator. p53 activates NGFR transcription, whereas NGFR inactivates p53 by promoting its MDM2-mediated ubiquitin-dependent proteolysis and by directly binding to its central DNA binding domain and preventing its DNA-binding activity. Inversely, NGFR ablation activates p53, consequently inducing apoptosis, attenuating survival, and reducing clonogenic capability of cancer cells, as well as sensitizing human cancer cells to chemotherapeutic agents that induce p53 and suppressing mouse xenograft tumor growth. NGFR is highly expressed in human glioblastomas, and its gene is often amplified in breast cancers with wild type p53. Altogether, our results demonstrate that cancers hijack NGFR as an oncogenic inhibitor of p53.
EWS‐FLI1 impairs aryl hydrocarbon receptor activation by blocking tryptophan breakdown via the kynurenine pathway
Authors: Mutz Cornelia N. , Schwentner Raphaela , Kauer Maximilian O. , Katschnig Anna M. , Kromp Florian , Aryee Dave N. T. , Erhardt Sophie , Goiny Michel , Alonso Javier , Fuchs Dietmar , Kovar Heinrich
Published: June 2016

Ewing sarcoma (ES) is an aggressive pediatric tumor driven by the fusion protein EWS‐FLI1. We report that EWS‐FLI1 suppresses TDO2‐mediated tryptophan (TRP) breakdown in ES cells. Gene expression and metabolite analyses reveal an EWS‐FLI1‐dependent regulation of TRP metabolism. TRP consumption increased in the absence of EWS‐FLI1, resulting in kynurenine and kynurenic acid accumulation, both aryl hydrocarbon receptor (AHR) ligands. Activated AHR binds to the promoter region of target genes. We demonstrate that EWS‐FLI1 knockdown results in AHR nuclear translocation and activation. Our data suggest that EWS‐FLI1 suppresses autocrine AHR signaling by inhibiting TDO2‐catalyzed TRP breakdown.
Interannual variability in net community production at the Western Antarctic Peninsula region (1997–2014)
Authors: Li Zuchuan , Cassar Nicolas , Huang Kuan , Ducklow Hugh , Schofield Oscar
Published: June 2016

In this study, we examined the interannual variability of net community production (NCP) in the Western Antarctic Peninsula (WAP) using in situ O2/Ar‐NCP estimates (2008–2014) and satellite data (SeaWiFS and MODIS‐Aqua) from 1997 to 2014. We found that NCP generally first peaks offshore and follows sea‐ice retreat from offshore to inshore. Annually integrated NCP (ANCP) displays an onshore‐to‐offshore gradient, with coastal and shelf regions up to 8 times more productive than offshore regions. We examined potential drivers of interannual variability in the ANCP using an Empirical Orthogonal Function (EOF) analysis. The EOF's first mode explains ∼50% of the variance, with high interannual variability observed seaward of the shelf break. The first principal component is significantly correlated with the day of sea‐ice retreat (R = −0.58,p < 0.05), as well as the Southern Annular Mode (SAM) and El Niño Southern Oscillation (ENSO) climate indices in austral spring. Although the most obvious pathway by which the day of sea‐ice retreat influences NCP is by controlling light availability early in the growing season, we found that the effect of day of sea‐ice retreat on NCP persists throughout the growing season, suggesting that additional controls, such as iron availability, are preconditioned or correlated to the day of sea‐ice retreat.
Scalable subsurface inverse modeling of huge data sets with an application to tracer concentration breakthrough data from magnetic resonance imaging
Authors: Lee Jonghyun , Yoon Hongkyu , Kitanidis Peter K. , Werth Charles J. , Valocchi Albert J.
Published: June 2016

Characterizing subsurface properties is crucial for reliable and cost‐effective groundwater supply management and contaminant remediation. With recent advances in sensor technology, large volumes of hydrogeophysical and geochemical data can be obtained to achieve high‐resolution images of subsurface properties. However, characterization with such a large amount of information requires prohibitive computational costs associated with “big data” processing and numerous large‐scale numerical simulations. To tackle such difficulties, the principal component geostatistical approach (PCGA) has been proposed as a “Jacobian‐free” inversion method that requires much smaller forward simulation runs for each iteration than the number of unknown parameters and measurements needed in the traditional inversion methods. PCGA can be conveniently linked to any multiphysics simulation software with independent parallel executions. In this paper, we extend PCGA to handle a large number of measurements (e.g., 106 or more) by constructing a fast preconditioner whose computational cost scales linearly with the data size. For illustration, we characterize the heterogeneous hydraulic conductivity (K) distribution in a laboratory‐scale 3‐D sand box using about 6 million transient tracer concentration measurements obtained using magnetic resonance imaging. Since each individual observation has little information on the K distribution, the data were compressed by the zeroth temporal moment of breakthrough curves, which is equivalent to the mean travel time under the experimental setting. Only about 2000 forward simulations in total were required to obtain the best estimate with corresponding estimation uncertainty, and the estimated K field captured key patterns of the original packing design, showing the efficiency and effectiveness of the proposed method.
Solar cycle variability in mean thermospheric composition and temperature induced by atmospheric tides
Authors: Jones M. , Forbes J. M. , Hagan M. E.
Published: June 2016

In this paper we demonstrate that dissipation of upward propagating tides produces significant changes in the mean temperature of the thermosphere, ranging from +19 K at solar minimum to −15 K at solar maximum in the equatorial region. Our methodology consists of measuring the differential response of the thermosphere‐ionosphere‐electrodynamics general circulation model (TIE‐GCM) under solar minimum and solar maximum conditions to constant tidal forcing at its 97 km lower boundary, as specified by the observationally based Climatological Tidal Model of the Thermosphere. Diagnosis of the model reveals that these changes are mainly driven by 5.3 μm nitric oxide (NO) cooling, which more efficiently cools the thermosphere at solar maximum. The main role of the tides is to modify the mean molecular oxygen densities ([O2]) through tidal‐induced advective transport, which then lead to changes in NO densities through oxygen‐nitrogen chemistry. Through tidal‐induced changes in temperature and O, O2, and N2 densities, effects on the ionosphere are also quite substantial; tidal‐induced modifications to zonal‐mean F region peak electron densities (NmF2) are of order −10% at solar maximum and −30% at solar minimum in the equatorial region. Our results introduce an additional consideration when attributing long‐term changes in thermospheric temperature and electron densities to CO2 cooling effects alone; that is, dissipation of upward propagating tides may constitute an additional element of global change in the ionosphere‐thermosphere (IT) system.
Micromechanics of brittle faulting and cataclastic flow in Mount Etna basalt
Authors: Zhu Wei , Baud Patrick , Vinciguerra Sergio , Wong Teng‐fong
Published: June 2016

Understanding how the strength of volcanic rocks varies with stress state, pressure, and microstructural attributes is fundamental to understanding the dynamics and tectonics of a volcanic system and also very important in applications such as geothermics or reservoir management in volcanic environments. In this study we investigated the micromechanics of deformation and failure in basalt, focusing on samples from Mount Etna. We performed 65 uniaxial and triaxial compression experiments on nominally dry and water‐saturated samples covering a porosity range between 5 and 16%, at effective pressures up to 200 MPa. Dilatancy and brittle faulting were observed in all samples with porosity of 5%. Water‐saturated samples were found to be significantly weaker than comparable dry samples. Shear‐enhanced compaction was observed at effective pressures as low as 80 MPa in samples of 8% porosity. Microstructural data revealed the complex interplay of microcracks, pores, and phenocrysts on dilatant failure and inelastic compaction in basalt. The micromechanics of brittle failure is controlled by wing crack propagation under triaxial compression and by pore‐emanated cracking under uniaxial compression especially in the more porous samples. The mechanism of inelastic compaction in basalt is cataclastic pore‐collapse in agreement with a recent dual‐porosity model.
Modeling the QBO—Improvements resulting from higher‐model vertical resolution
Authors: Geller Marvin A. , Zhou Tiehan , Shindell D. , Ruedy R. , Aleinov I. , Nazarenko L. , Tausnev N. L. , Kelley M. , Sun S. , Cheng Y. , Field R. D. , Faluvegi G.
Published: June 2016

Using the NASA Goddard Institute for Space Studies (GISS) climate model, it is shown that with proper choice of the gravity wave momentum flux entering the stratosphere and relatively fine vertical layering of at least 500 m in the upper troposphere‐lower stratosphere (UTLS), a realistic stratospheric quasi‐biennial oscillation (QBO) is modeled with the proper period, amplitude, and structure down to tropopause levels. It is furthermore shown that the specified gravity wave momentum flux controls the QBO period whereas the width of the gravity wave momentum flux phase speed spectrum controls the QBO amplitude. Fine vertical layering is required for the proper downward extension to tropopause levels as this permits wave‐mean flow interactions in the UTLS region to be resolved in the model. When vertical resolution is increased from 1000 to 500 m, the modeled QBO modulation of the tropical tropopause temperatures increasingly approach that from observations, and the “tape recorder” of stratospheric water vapor also approaches the observed. The transport characteristics of our GISS models are assessed using age‐of‐air and N2O diagnostics, and it is shown that some of the deficiencies in model transport that have been noted in previous GISS models are greatly improved for all of our tested model vertical resolutions. More realistic tropical‐extratropical transport isolation, commonly referred to as the “tropical pipe,” results from the finer vertical model layering required to generate a realistic QBO.
Dynamics of Repeated Interviews with Children
Authors: Waterhouse Genevieve F. , Ridley Anne M. , Bull Ray , La Rooy David , Wilcock Rachel
Published: June 2016

Concerns regarding repeat interviews with child witnesses include greater use of suggestive questions in later interviews due to bias, and that children may appear inconsistent and, therefore, be judged as less reliable in court. UK transcripts of first and second interviews with 21 child victims/witnesses (conducted by qualified interviewers) were coded for question types and child responses. Interviewers were consistent in their proportional use of question types across interviews. Furthermore, children were as informative in second interviews as in first, mostly providing new details consistent with their prior recall. Despite the apparent lack of training in conducting repeated interviews, no negative effects were found; second interviews appeared to be conducted as well as initial interviews, and children provided new details without many contradictions. It is suggested that when a child's testimony is paramount for an investigation, a well‐conducted supplementary interview may be an effective way of gaining further investigative leads.Copyright © 2016 John Wiley & Sons, Ltd.
Dynamics of Strong Coupling between J‐Aggregates and Surface Plasmon Polaritons in Subwavelength Hole Arrays
Authors: Wang Hai , Wang Hai‐Yu , Bozzola Angelo , Toma Andrea , Panaro Simone , Raja Waseem , Alabastri Alessandro , Wang Lei , Chen Qi‐Dai , Xu Huai‐Liang , De Angelis Francesco , Sun Hong‐Bo , Zaccaria Remo Proietti
Published: June 2016

A prototypical hybrid system formed by strong coupled gold hole arrays and J‐aggregate molecules is investigated by using both steady‐state spectroscopic method and ultrafast pump‐probe approach. In particular, the plasmonic response of the device has been tuned by modifying its periodicity thus to achieve the strongest possible coupling regime. It is found that in the transient absorption spectra, under upper band excitation, the bleaching signal from uncoupled J‐aggregate molecules completely disappears. Instead, two distinctive period dependent bleaching bands are formed, clearly fingerprint of the hybrid exciton‐plasmon state. The dynamics of these bands is also directly analyzed. A remarkable long lifetime is found especially for the upper band, corresponding to the presence of a trap state in its transient absorption spectra under resonance excitation. Such unique feature should provide a new approach to control quantum‐mechanical states under coherent coupling.
Flow pattern transition in gas‐liquid downflow through narrow vertical tubes
Authors: Kumar Amit , Bhowmik Satyabrata , Ray Subhabrata , Das Gargi
Published: June 2016

The present report studies on the flow pattern transitions during vertical air water downflow through millichannels (0.83 ≤ Eötvös no. ≤ 20.63). Four basic flow patterns namely falling film flow, slug flow, bubbly flow, and annular flow are observed in the range of experimental conditions studied and their range of existence has been noted to vary with tube diameter and phase velocities. Based on experimental observations, phenomenological models are proposed to predict the transition boundaries between adjacent patterns. These have been validated with experimental flow pattern maps from the present experiments. Thus the study formalizes procedure for developing a generalized flow pattern map for gas‐liquid downflow in narrow tubes. © 2016 American Institute of Chemical Engineers AIChE J, 63: 792–800, 2017
Secondhand smoke in the operating room? Precautionary practices lacking for surgical smoke
Authors: Steege Andrea L. , Boiano James M. , Sweeney Marie H.
Published: June 2016

Background

Consensus organizations, government bodies, and healthcare organization guidelines recommend that surgical smoke be evacuated at the source by local exhaust ventilation (LEV) (i.e., smoke evacuators or wall suctions with inline filters).

Methods

Data are from NIOSH's Health and Safety Practices Survey of Healthcare Workers module on precautionary practices for surgical smoke.

Results

Four thousand five hundred thirty‐three survey respondents reported exposure to surgical smoke: 4,500 during electrosurgery; 1,392 during laser surgery procedures. Respondents were mainly nurses (56%) and anesthesiologists (21%). Only 14% of those exposed during electrosurgery reported LEV was always used during these procedures, while 47% reported use during laser surgery. Those reporting LEV was always used were also more likely to report training and employer standard procedures addressing the hazards of surgical smoke. Few respondents reported use of respiratory protection.

Conclusions

Study findings can be used to raise awareness of the marginal use of exposure controls and impediments for their use. Am. J. Ind. Med. 59:1020–1031, 2016. Published 2016. This article is a U.S. Government work and is in the public domain in the USA
Die Basislinie der chemischen Verschiebung in Hochdruck‐NMR‐Spektren von Proteinen
Authors: Frach Roland , Kibies Patrick , Böttcher Saraphina , Pongratz Tim , Strohfeldt Steven , Kurrmann Simon , Koehler Joerg , Hofmann Martin , Kremer Werner , Kalbitzer Hans Robert , Reiser Oliver , Horinek Dominik , Kast Stefan M.
Published: June 2016

Die Hochdruck‐NMR‐Spektroskopie ist wichtig für die Detektion selten auftretender Proteinzustände mithilfe der Druckabhängigkeit der chemischen Verschiebung. Für die Analyse dieser Verschiebungen muss allerdings der Ursprung der beobachteten Druckabhängigkeit verstanden werden. Es werden Hochdruck‐NMR‐Ergebnisse für 15N‐angereichertes N‐Methylacetamid (NMA) in Wasser als Modell für Peptidbindungen vorgestellt. Diese werden mit quantenchemischen Berechnungen der zugehörigen magnetischen Parameter unter Verwendung eines druckempfindlichen Solvensmodells kombiniert. Die Analyse der theoretischen Ergebnisse für NMA und den experimentellen Standard DSS zeigt, dass ein wesentlicher Teil der Änderungen der chemischen Verschiebung auf die solvensinduzierte elektronische Polarisation des Rückgrats zurückgeht. Weiterhin zeigt die magnetische Abschirmung von DSS nur geringe Empfindlichkeit für Druckänderungen, weswegen der DSS‐Standard ein zuverlässiger Sensor druckabhängiger solvensvermittelter Variationen des lokalen magnetischen Felds ist.
Generalizing the Concept of Specific Compound Formulation Additives towards Non‐Fluorescent Drugs: A Solubilization Study on Potential Anti‐Alzheimer‐Active Small‐Molecule Compounds
Authors: Lawatscheck Carmen , Pickhardt Marcus , Wieczorek Sebastian , Grafmüller Andrea , Mandelkow Eckhard , Börner Hans G.
Published: June 2016

Tailor‐made compound formulation additives enable the testing of potential drugs with undesirable pharmacological profiles. A combinatorial approach using Raman microscopy as the readout method is presented to select peptide sequences from large one‐bead‐one‐compound libraries. The resulting peptide–PEG conjugates solubilize potential prophylactic and therapeutic anti‐Alzheimer compounds and can be used as specific additives not only for fluorescent but also for non‐fluorescent compounds.
Remarkable Improvement in the Mechanical Properties and CO2 Uptake of MOFs Brought About by Covalent Linking to Graphene
Authors: Kumar Ram , Raut Devaraj , Ramamurty Upadrasta , Rao C. N. R.
Published: June 2016

Metal–organic frameworks (MOFs) are exceptional as gas adsorbents but their mechanical properties are poor. We present a successful strategy to improve the mechanical properties along with gas adsorption characteristics, wherein graphene (Gr) is covalently bonded with M/DOBDC (M=Mg2+, Ni2+, or Co2+, DOBDC=2,5‐dioxido‐1,4‐benzene dicarboxylate) MOFs. The surface area of the graphene–MOF composites increases up to 200–300 m2 g−1 whereas the CO2 uptake increases by ca. 3–5 wt % at 0.15 atm and by 6–10 wt % at 1 atm. What is significant is that the composites exhibit improved mechanical properties. In the case of Mg/DOBDC, a three‐fold increase in both the elastic modulus and hardness with 5 wt % graphene reinforcement is observed. Improvement in both the mechanical properties and gas adsorption characteristics of porous MOFs on linking them to graphene is a novel observation and suggests a new avenue for the design and synthesis of porous materials.
Viscoelastic properties of borax loaded CMC‐g‐cl‐poly(AAm) hydrogel composites and their boron nutrient release behavior
Authors: Sarkar Dhruba Jyoti , Singh Anupama , Gaur Shalini Rudra , Shenoy Aroon V
Published: June 2016

Borax (Na2B4O7, 10.5% Boron) loaded CMC‐g‐cl‐poly(AAm) hydrogel composites were prepared byin situgrafting of acrylamide on to sodium carboxymethyl cellulose in the presence of borax by free radical polymerization technique to develop slow boron (B) delivery device. The composition, morphology, and mechanical properties of synthesized composites were studied by X‐ray diffraction, Fourier transform infrared spectroscopy, scanning electron microscopy, texture analyser, and dynamic shear rheometer. Characterization revealed formation of borate ion () from borax during polymerization reaction leading to extensive crosslinking of cellulosic chains and generation of mechanically strong composite hydrogels. Dynamic release offrom the synthesized composites hydrogels followed Fickian diffusion mechanism and composites with high mechanical strength resulted in slow release of B. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci.2016,133, 43969.
Responding to Global Challenges in Food, Energy, Environment and Water: Risks and Options Assessment for Decision‐Making
Authors: Grafton R. Quentin , McLindin Mahala , Hussey Karen , Wyrwoll Paul , Wichelns Dennis , Ringler Claudia , Garrick Dustin , Pittock Jamie , Wheeler Sarah , Orr Stuart , Matthews Nathanial , Ansink Erik , Aureli Alice , Connell Daniel , De Stefano Lucia , Dowsley Kate , Farolfi Stefano , Hall Jim , Katic Pamela , Lankford Bruce , Leckie Hannah , McCartney Matthew , Pohlner Huw , Ratna Nazmun , Rubarenzya Mark Henry , Sai Raman Shriman Narayan , Wheeler Kevin , Williams John
Published: June 2016

We analyse the threats of global environmental change, as they relate to food security. First, we review three discourses: (i) ‘sustainable intensification’, or the increase of food supplies without compromising food producing inputs, such as soils and water; (ii) the ‘nexus’ that seeks to understand links across food, energy, environment and water systems; and (iii) ‘resilience thinking’ that focuses on how to ensure the critical capacities of food, energy and water systems are maintained in the presence of uncertainties and threats. Second, we build on these discourses to present the causal, risks and options assessment for decision‐making process to improve decision‐making in the presence of risks. The process provides a structured, but flexible, approach that moves from problem diagnosis to better risk‐based decision‐making and outcomes by responding to causal risks within and across food, energy, environment and water systems.
Chemical Composition and Interpopulation Variability of Essential Oils of Taxus baccata L. from Serbia
Authors: Stefanović Milena , Ristić Mihailo , Popović Zorica , Matić Rada , Nikolić Biljana , Vidaković Vera , Obratov‐Petković Dragica , Bojović Srdjan
Published: June 2016

The composition of the essential oil of the twigs and needles of Taxus baccata L. from three natural populations in Serbia has been determined by GC/MS analysis. Of the 91 detected compounds, 87 were identified. The most abundant compound classes were aliphatic alcohols, terpenes, aliphatic hydrocarbons, and aliphatic aldehydes, which together comprised ca. 86.92% of the total oil composition. The dominant constituents were oct‐1‐en‐3‐ol (23.48%), (3Z)‐hex‐3‐en‐1‐ol (11.46%; aliphatic alcohols), and myrtenol (11.38%; oxygenated monoterpene). The PCA of 22 selected compounds revealed differentiations of populations based on geographic distribution. The CA showed that Populations I and II from the Dinaric Alps were similar, and that Population III from the Balkan mountain system was distinct. This was the first investigation of interpopulation variability of T. baccata populations based on essential oil composition. The results of this study were compared with those of previous studies concerning volatile compounds produced by Taxus species. The results indicate that the essential oil content of T. baccata populations from this study is unique, mostly resembling the population from southeast Serbia.
Synthesis and Rearrangement of P‐Nitroxyl‐Substituted PIII and PV Phosphanes: A Combined Experimental and Theoretical Case Study
Authors: Heurich Tobias , Qu Zheng‐Wang , Nožinović Senada , Schnakenburg Gregor , Matsuoka Hideto , Grimme Stefan , Schiemann Olav , Streubel Rainer
Published: June 2016

Low‐temperature generation of P‐nitroxyl phosphane 2 (Ph2POTEMP), which was obtained by the reaction of Ph2PH (1) with two equivalents of TEMPO, is presented. Upon warming, phosphane 2 decomposed to give P‐nitroxyl phosphane P‐oxide 3 (Ph2P(O)OTEMP) as one of the final products. This facile synthetic protocol also enabled access to P‐sulfide and P‐borane derivatives 7 and 13, respectively, by using Ph2P(S)H (6) or Ph2P(BH3)H (11) and TEMPO. Phosphane sulfide 7 revealed a rearrangement to phosphane oxide 8 (Ph2P(O)STEMP) in CDCl3 at ambient temperature, whereas in THF, thermal decomposition of sulfide 7 yielded salt 10 ([TEMP‐H2][Ph2P(S)O]). As well as EPR and detailed NMR kinetic studies, indepth theoretical studies provided an insight into the reaction pathways and spin‐density distributions of the reactive intermediates.
Nonamplification ERBB2 genomic alterations in 5605 cases of recurrent and metastatic breast cancer: An emerging opportunity for anti‐HER2 targeted therapies
Authors: Ross Jeffrey S. , Gay Laurie M. , Wang Kai , Ali Siraj M. , Chumsri Saranya , Elvin Julia A. , Bose Ron , Vergilio Jo‐Anne , Suh James , Yelensky Roman , Lipson Doron , Chmielecki Juliann , Waintraub Stanley , Leyland‐Jones Brian , Miller Vincent A. , Stephens Philip J.
Published: June 2016

BACKGROUND

Activating, nonamplification ERBB2 mutations (ERBB2mut) are not detected by immunohistochemistry (IHC) or fluorescence in situ hybridization (FISH), but are detected by DNA sequencing and may predict clinical responses to human epidermal growth factor receptor (HER2)‐targeted therapy. The authors queried 5605 advanced/metastatic breast cancers (mBC) to uncover the frequency of ERBB2mut genomic alterations. Clinical responses to anti‐HER2 therapeutics were identified.

METHODS

DNA was extracted from 40 µm of formalin‐fixed paraffin‐embedded (FFPE) sections. Comprehensive genomic profiling (CGP) was used to evaluate up to 315 genes (592× mean coverage depth). Results were analyzed for base substitutions, short indels, copy number changes, and selected rearrangements.

RESULTS

Of 5605 cases, 698 (12.5%) featured ERBB2 alterations, including 596 (10.6%) ERBB2 amplifications (ERBB2amp) and 138 (2.4%) ERBB2mut; 38 cases (0.7%) had co‐occurring ERBB2amp and ERBB2mut. ERBB2mut predominantly affected the kinase (124 cases; 90%) or extracellular (15 cases; 11%) domains. Both primary BC (52 cases; 38%) and metastatic site biopsies (86 cases; 62%) were found to harbor ERBB2mut, which were distributed across carcinoma not otherwise specified (NOS) (69 cases; 50%), invasive ductal carcinoma (IDC) (40 cases; 29%), invasive lobular carcinoma (ILC) (27 cases; 20%), and mucinous mBC (2 cases; 1%). Genes commonly coaltered with ERBB2 were tumor protein 53 (TP53) (49%); phosphatidylinositol 3‐kinase catalytic subunit alpha (PIK3CA) (42%); cadherin 1, type 1 (CDH1) (37%); MYC (17%); and cyclin D1 protein (CCND1) (16%). CDH1 mutations were enriched in ERBB2mut mBC (P<0.0006) and associated with recurrent mBC. Selected patients with ERBB2mut, without ERBB2amp, who responded to anti‐HER2 targeted therapies are presented herein.

CONCLUSIONS

Within this large series, 1.8% of cases harbored ERBB2mut, which are undetectable by standard‐of‐care IHC or FISH tests. Metastatic BC driven by ERBB2mut respond to anti‐HER2 targeted therapies, and expanding clinical trials designed to detect ERBB2mut by CGP and optimize targeted treatments are warranted. Cancer 2016. © 2016 American Cancer Society. Cancer 2016;122:2654–2662. © 2016 American Cancer Society.
Timing and type of immune checkpoint therapy affect the early radiographic response of melanoma brain metastases to stereotactic radiosurgery
Authors: Qian Jack M. , Yu James B. , Kluger Harriet M. , Chiang Veronica L. S.
Published: June 2016

BACKGROUND

Growing evidence suggests that immunotherapy and radiation therapy can be synergistic in the treatment of cancer. This study was performed to determine the effect of the relative timing and type of immune checkpoint therapy on the response of melanoma brain metastases (BrMets) to treatment with stereotactic radiosurgery (SRS).

METHODS

Seventy‐five melanoma patients with 566 BrMets were treated with both SRS and immune checkpoint therapy between 2007 and 2015 at a single institution. Immunotherapy and radiosurgery treatment of any single lesion were considered concurrent if SRS was administered within 4 weeks of immunotherapy. The impact of the timing and type of immunotherapy on the lesional response was determined with the Wilcoxon rank‐sum test, which was used to compare the median percent lesion volume change 1.5, 3, and 6 months after SRS treatment, with significance determined by P = .0167 according to the Bonferroni correction for multiple comparisons.

RESULTS

Concurrent use of immunotherapy and SRS resulted in a significantly greater median percent reduction in the lesion volume at 1.5 (−63.1% vs −43.2%, P < .0001), 3 (−83.0% vs −52.8%, P < .0001), and 6 months (−94.9% vs −66.2%, P < .0001) in comparison with nonconcurrent therapy. The median percent reduction in the lesion volume was also significantly greater for anti–programmed cell death protein 1 (anti–PD‐1) than anti–cytotoxic T‐lymphocyte‐associated protein 4 (anti–CTLA‐4) at 1.5 (−71.1% vs −48.2%, P < .0001), 3 (−89.3% vs −66.2%, P < .0001), and 6 months (−95.1% vs −75.9%, P = .0004).

CONCLUSIONS

The administration of immunotherapy within 4 weeks of SRS results in an improved lesional response of melanoma BrMets in comparison with treatment separated by longer than 4 weeks. Anti–PD‐1 therapy also results in a greater lesional response than anti–CTLA‐4 after SRS. Cancer 2016;122:3051‐3058. © 2016 American Cancer Society.
Painting of Arabidopsis Chromosomes with Chromosome‐Specific BAC Clones
Authors: Mandáková Terezie , Lysak Martin A.
Published: June 2016

Chromosome painting (CP) refers to fluorescence in situ hybridization (FISH) of chromosome‐specific DNA probes to identify large chromosome regions, chromosome arms, and whole chromosomes. For CP and CCP (comparative chromosome painting) in plants, most often, contigs of chromosome‐specific bacterial artificial chromosomes (BAC) from the species of origin or a related species are used as painting probes. CP enables visualization and tracing of particular chromosome regions and/or chromosomes throughout all mitotic and meiotic stages as well as the corresponding interphase chromosome territories. CCP enables identification of large‐scale homeologous chromosome regions and chromosomes shared among two or more species. Here, a step‐by‐step protocol for carrying out CP in Arabidopsis thaliana (Arabidopsis) and CCP in other crucifer taxa based on the use of Arabidopsis chromosome‐specific BAC contigs is described. © 2016 by John Wiley & Sons, Inc.
Applying autonomy with bandwidth allocation models
Authors: Reale Rafael Freitas , Bezerra Romildo Martins da S. , Martins Joberto S. B.
Published: June 2016

Bandwidth Allocation Models (BAMs) are resource allocation methods used for networks in general. BAMs are currently applied for handling resources such as bandwidth allocation in MPLS DS‐TE networks (LSP setup). In general, BAMs define resource restrictions by ‘class’ and allocate the available resources on demand. This is frequently necessary to manage large and complex systems like routing networks. G‐BAM is a new generalized BAM that, by configuration, incorporates the ‘behavior’ of existing BAMs (MAM, RDM, G‐RDM and AllocTC‐Sharing). In effect, any current available BAM ‘behavior’ is reproduced by G‐BAM by simply adjusting its configuration parameters. This paper focuses on investigating the applicability of using autonomy together with BAMs for improve performance and facilitating the management of MPLS DS‐TE networks. It is investigated the applicability of ‘BAM switching’ using a framework with autonomic characteristics. In brief, it is investigated the switching among ‘BAM behaviors’ and BAM's reconfiguration with distinct network traffic scenarios by using G‐BAM. Simulation results suggest that the autonomic switching of ‘BAM behaviors’ based on high‐level management rules (Service Level Agreements, Quality of Service (QoS) or other police) may result in improving overall network management and operational parameters such as link utilization and preemption. Copyright © 2016 John Wiley & Sons, Ltd.
Inferring invasive species abundance using removal data from management actions
Authors: Davis Amy J. , Hooten Mevin B. , Miller Ryan S. , Farnsworth Matthew L. , Lewis Jesse , Moxcey Michael , Pepin Kim M.
Published: June 2016

Evaluation of the progress of management programs for invasive species is crucial for demonstrating impacts to stakeholders and strategic planning of resource allocation. Estimates of abundance before and after management activities can serve as a useful metric of population management programs. However, many methods of estimating population size are too labor intensive and costly to implement, posing restrictive levels of burden on operational programs. Removal models are a reliable method for estimating abundance before and after management using data from the removal activities exclusively, thus requiring no work in addition to management. We developed a Bayesian hierarchical model to estimate abundance from removal data accounting for varying levels of effort, and used simulations to assess the conditions under which reliable population estimates are obtained. We applied this model to estimate site‐specific abundance of an invasive species, feral swine (Sus scrofa), using removal data from aerial gunning in 59 site/time‐frame combinations (480–19,600 acres) throughout Oklahoma and Texas, USA. Simulations showed that abundance estimates were generally accurate when effective removal rates (removal rate accounting for total effort) were above 0.40. However, when abundances were small (<50) the effective removal rate needed to accurately estimates abundances was considerably higher (0.70). Based on our post‐validation method, 78% of our site/time frame estimates were accurate. To use this modeling framework it is important to have multiple removals (more than three) within a time frame during which demographic changes are minimized (i.e., a closed population; ≤3 months for feral swine). Our results show that the probability of accurately estimating abundance from this model improves with increased sampling effort (8+ flight hours across the 3‐month window is best) and increased removal rate. Based on the inverse relationship between inaccurate abundances and inaccurate removal rates, we suggest auxiliary information that could be collected and included in the model as covariates (e.g., habitat effects, differences between pilots) to improve accuracy of removal rates and hence abundance estimates.
Distribution and diversity of diatom assemblages in surficial sediments of shallow lakes in Wapusk National Park (Manitoba, Canada) region of the Hudson Bay Lowlands
Authors: Jacques Olivier , Bouchard Frédéric , MacDonald Lauren A. , Hall Roland I. , Wolfe Brent B. , Pienitz Reinhard
Published: June 2016

The hydrology of shallow lakes (and ponds) located in the western Hudson Bay Lowlands (HBL) is sensitive to climate warming and associated permafrost thaw. However, their biological characteristics are poorly known, which hampers effective aquatic ecosystem monitoring. Located in northern Manitoba along the southwestern coast of Hudson Bay, Wapusk National Park (WNP) encompasses numerous shallow lakes representative of the subarctic zone. We analyzed the distribution and diversity of diatom (microscopic algae; class Bacillariophyceae) assemblages in surficial sediments of 33 lakes located in three different ecozones spanning a vegetation gradient, from NE to SW: the Coastal Fen (CF), the Interior Peat Plateau (IPP), and the Boreal Spruce Forest (BSF). We found significant differences (P < 0.05) in diatom community composition between CF and IPP lakes, and CF and BSF lakes, but not between IPP and BSF lakes. These results are consistent with water chemistry measurements, which indicated distinct limnological conditions for CF lakes. Diatom communities in CF lakes were generally dominated by alkaliphilous taxa typical of waters with medium to high conductivity, such as Nitzschia denticula. In contrast, several IPP and BSF lakes were dominated by acidophilous and circumneutral diatom taxa with preference for low conductivity (e.g., Tabellaria flocculosa, Eunotia mucophila, E. necompacta var. vixcompacta). This exploratory survey provides a first detailed inventory of the diatom assemblages in the WNP region needed for monitoring programs to detect changes in shallow lake ecosystems and ecozonal shifts in response to climate variations.
Proton Conductivities Manipulated by the Counter‐Anions in 2D Co‐Ca Coordination Frameworks
Authors: Bao Song‐Song , Wu Yu‐Xuan , Li Nan‐Zhu , Zheng Li‐Min
Published: June 2016

Three new layered Co‐Ca phosphonates are reported, namely, [CoCa(notpH2)(H2O)2]X·nH2O (CoCa‐X·nH2O; X = Cl–, NO3–, PF6–), where notpH6 is 1,4,7‐triazacyclononane‐1,4,7‐triyltris(methylenephosphonic acid) [C9H18N3(PO3H2)3]. The layer topology of these compounds are identical to that of [CoCa(notpH2)(H2O)2]ClO4·nH2O (CoCa‐ClO4·nH2O). The most significant difference lies in the counter‐anions, which not only have different size and shape but also show different capabilities towards hydrogen bonding. Consequently, the number of lattice water molecules and the hydrogen‐bond networks between the layers can be varied depending on the particular counter‐anion. AC impedance measurements reveal that the proton conductivities at 25 °C and 95 % relative humidity (RH) follow the sequence: CoCa‐Cl·nH2O > CoCa‐NO3·nH2O > CoCa‐PF6·nH2O ≈ CoCa‐ClO4·nH2O. Compound CoCa‐Cl·nH2O shows the highest proton conductivity of 1.40 × 10–4 S cm–1 at 25 °C and 95 % RH, which is one order of magnitude higher than those of CoCa‐PF6·nH2O (1.39 × 10–5 S cm–1) and CoCa‐ClO4·nH2O (1.55 × 10–5 S cm–1).
Anomalous Thermal Expansion and Luminescence Thermochromism in Silver(I) Dicyanamide
Authors: Hodgson Sarah A. , Hunt Sarah J. , Sørensen Thomas Just , Thompson Amber L. , Reynolds Emily M. , Faulkner Stephen , Goodwin Andrew L.
Published: June 2016

We study mechanical flexibility and its link to optical properties in the dense metal–organic framework silver(I) dicyanamide {Ag[N(CN)2], Ag(dca)}. We show that the system exhibits polymorph‐independent anomalous thermal expansion behaviour and find a linear variation in the relative intensity of emission bands with temperature, indicative of thermochromism in the Ag‐centered luminescence.
Palladium‐Catalyzed C(sp2)–H Bond Alkylation of Ketoximes by Using the Ring‐Opening of Epoxides
Authors: Li Dan‐Dan , Niu Liang‐Feng , Ju Zhi‐Yu , Xu Zhihong , Wu Changzeng
Published: June 2016

A palladium‐catalyzed ortho‐directed alkylation of O‐methyl ketoximes that proceeds through a regioselective ring‐opening reaction of epoxides has been demonstrated. This C(sp2)–H activation/alkylation protocol was carried out in pivalic acid/1,1,1,3,3,3‐hexafluoro‐2‐propanol (PivOH/HFIP, 2:8) as the solvent and was applied to various O‐methyl ketoximes that contain either electron‐donating or electron‐withdrawing groups. Moreover, different types of epoxides were used in this alkylation reaction, which proceeded smoothly to give the corresponding products in moderate to good yields.
Single‐Electron‐Transfer‐Induced Coupling of Alkylzinc Reagents with Aryl Iodides
Authors: Okura Keisho , Shirakawa Eiji
Published: June 2016

Alkylzinc reagents prepared from an alkyllithium and zinc iodide were found to undergo coupling with aryl and alkenyl iodides in the presence of LiI in a mixed solvent consisting of THF and diglyme (1:1). Alkyllithiums, prepared by halogen–lithium exchange between an alkyl iodide and tert‐butyllithium, are also converted to alkylarenes through alkylzinc reagents.
Palladium‐Catalyzed Regioselective C–H Acetoxylation of 2‐Aryloxypyridines with 2‐Pyridyloxy as a Removable Directing Group
Authors: Wang Liang , Pan Liang , Huang Yibo , Chen Qun , He Mingyang
Published: June 2016

A simple and regioselective palladium‐catalyzed ortho‐C(sp2)–H acetoxylation of 2‐aryloxypyridines with PhI(OAc)2 as both the oxidant and acetate source has been developed. The mono‐ and di‐acetoxylated products can be achieved by tuning the equivalents of PhI(OAc)2 and the reaction temperature. A wide range of 2‐aryloxypyridines is tolerated. Moreover, 2‐pyridyloxyl and acetyl groups can be easily removed, which provides straightforward access to poly‐substituted phenols.
Relationship among mercury concentration, growth rate, and condition of northern pike: A tautology resolved?
Authors: Sandheinrich Mark B. , Drevnick Paul E.
Published: June 2016

Methylmercury is a bioaccumulative contaminant that biomagnifies in aquatic food webs and adversely affects the health of freshwater fish. Previous studies have documented an inverse relationship between fish condition and concentration of mercury in fish. However, this relationship may be a result of slow-growing fish accumulating large amounts of methylmercury rather than the effects of methylmercury on fish condition and growth. An evaluation was conducted of the relationship among fish condition, growth, and mercury concentration in northern pike Esox lucius from 26 lakes in the western region of the Laurentian Great Lakes (USA–Canada). The relative weight (an index of fish condition) of northern pike was inversely related to mercury concentration in the axial muscle. The concentration of mercury in standard-size northern pike increased with fish age and suggested that fast-growing fish accumulated less mercury than slow-growing fish. However, there was no relationship between the mean relative weight of northern pike in each population and mean age or mercury concentration of standard-size northern pike. These results suggest that the relationship between mercury and fish condition is not because of the effects of mercury on rate of growth, but rather because slow-growing fish bioaccumulate greater concentrations of mercury than fast-growing fish of the same length. Environ Toxicol Chem 2016;35:2910–2915. © 2016 SETAC
Elucidating the physiological and biochemical responses of different tobacco (Nicotiana tabacum) genotypes to lead toxicity
Authors: Maodzeka Antony , Hussain Nazim , Wei Liquan , Zvobgo Gerald , Mapodzeke James Mutemachani , Adil Muhammad Faheem , Jabeen Salma , Wang Feng , Jiang Lixi , Shamsi Imran Haider
Published: June 2016

In the present study, the effects of lead (Pb) uptake and toxicity were investigated in a hydroponic culture using 7 tobacco (Nicotiana tabacum L.) genotypes (Bina 1 [B1], Kutsaga Mammoth 10 [KM10], Nanjing 3 [N3], Kutsaga 35 [K35], Kutsaga E1 [KE1], Cocker 176 [C176], and Kutsaga RK6 [KRK6]) that differed in Pb tolerance. Lead was applied as a solution of Pb nitrate at concentrations of 0 μM, 10 μM, 250 μM, and 500 μM. After 4 wk of Pb treatment, tissue biomass and photosynthetic parameters were measured and elemental analysis was performed. The results showed decreases in growth and photosynthetic parameters with increases in Pb concentration compared with the control. The least reduction in the recorded physiological parameters was noted in K35, whereas the greatest reduction was observed in N3, which is an obvious indication of genotypic differences. Activities of peroxidase, catalase, and malondialdehyde increased significantly with increases in Pb concentration, with genotypes K35 and N3 showing the least and the greatest reduction, respectively. The results demonstrate the phototoxic nature of Pb on plants, and it can be concluded that in Pb-prone areas genotypes K35 and B1 can be used for cultivation because they can grow efficiently in the presence of high Pb concentrations while restricting Pb uptake in the aboveground parts, as seen by the higher Pb tolerance index. Environ Toxicol Chem 2017;36:175–181. © 2016 SETAC
Non‐intrusive reduced order modelling with least squares fitting on a sparse grid
Authors: Lin Z. , Xiao D. , Fang F. , Pain C. C. , Navon Ionel M.
Published: June 2016

This paper presents a non‐intrusive reduced order model for general, dynamic partial differential equations. Based upon proper orthogonal decomposition (POD) and Smolyak sparse grid collocation, the method first projects the unknowns with full space and time coordinates onto a reduced POD basis. Then we introduce a new least squares fitting procedure to approximate the dynamical transition of the POD coefficients between subsequent time steps, taking only a set of full model solution snapshots as the training data during the construction. Thus, neither the physical details nor further numerical simulations of the original PDE model are required by this methodology, and the level of non‐intrusiveness is improved compared with existing reduced order models. Furthermore, we take adaptive measures to address the instability issue arising from reduced order iterations of the POD coefficients. This model can be applied to a wide range of physical and engineering scenarios, and we test it on a couple of problems in fluid dynamics. It is demonstrated that this reduced order approach captures the dominant features of the high‐fidelity models with reasonable accuracy while the computation complexity is reduced by several orders of magnitude. Copyright © 2016 John Wiley & Sons, Ltd.