bluuebunny/crossref_metadata_2025 huggingface dataset:
Redox state‐dependent modulation of plant SnRK1 kinase activity differs from AMPK regulation in animals
Authors: Wurzinger Bernhard , Mair Andrea , Fischer‐Schrader Katrin , Nukarinen Ella , Roustan Valentin , Weckwerth Wolfram , Teige Markus
Published: September 2017

The evolutionarily highly conserved SNF1‐related protein kinase (SnRK1) protein kinase is a metabolic master regulator in plants, balancing the critical energy consumption between growth‐ and stress response‐related metabolic pathways. While the regulation of the mammalian [AMP‐activated protein kinase (AMPK)] and yeast (SNF1) orthologues of SnRK1 is well‐characterised, the regulation of SnRK1 kinase activity in plants is still an open question. Here we report that the activity and T‐loop phosphorylation of AKIN10, the kinase subunit of the SnRK1 complex, is regulated by the redox status. Although this regulation is dependent on a conserved cysteine residue, the underlying mechanism is different to the redox regulation of animal AMPK and has functional implications for the regulation of the kinase complex in plants under stress conditions.
Great Salt Lake (Utah) Microbialite δ13C, δ18O, and δ15N Record Fluctuations in Lake Biogeochemistry Since the Late Pleistocene
Authors: Newell D. L. , Jensen J. L. , Frantz C. M. , Vanden Berg M. D.
Published: September 2017

Extensive lacustrine microbialite deposits exposed along the shores of Great Salt Lake (GSL), Utah preserve a rich continental paleoenvironmental record. Newly‐reported microbialite carbon and oxygen stable isotope ratios in carbonate, nitrogen isotope ratios in organic matter, and organic matter radiocarbon ages archive paleolake hydrological and biogeochemical changes from the late Pleistocene through the Holocene. Positive correlations between δ18O and δ13C in ∼15 – 7.6 cal ka microbialite carbonate are consistent with a hydrologically closed‐basin lake with fluctuations in volume, chemistry, and associated changes in lake primary production. The δ15N of microbialite bulk organic matter (5 – 18 ‰ versus AIR) shows that the balance between nitrogen fixation and assimilation of dissolved inorganic nitrogen has varied significantly. Inverse δ18O and δ13C correlations in combination with high δ15N in some carbonate deposits may imply periods of higher salinity and stable lake stratification similar to modern GSL conditions. We compare our C and O data sets with Pleistocene Lake Bonneville carbonate stable isotope records and demonstrate progressive development of spatially‐isolated hydrological basins during the shift to warmer and drier conditions in the Holocene.
Arctic Deep Water Ferromanganese‐Oxide Deposits Reflect the Unique Characteristics of the Arctic Ocean
Authors: Hein James R. , Konstantinova Natalia , Mikesell Mariah , Mizell Kira , Fitzsimmons Jessica N. , Lam Phoebe J. , Jensen Laramie T. , Xiang Yang , Gartman Amy , Cherkashov Georgy , Hutchinson Deborah R. , Till Claire P.
Published: September 2017

Little is known about marine mineral deposits in the Arctic Ocean, an ocean dominated by continental shelf and basins semi‐closed to deep‐water circulation. Here, we present data for ferromanganese crusts and nodules collected from the Amerasia Arctic Ocean in 2008, 2009, and 2012 (HLY0805, HLY0905, and HLY1202). We determined mineral and chemical compositions of the crusts and nodules and the onset of their formation. Water column samples from the GEOTRACES program were analyzed for dissolved and particulate scandium concentrations, an element uniquely enriched in these deposits. The Arctic crusts and nodules are characterized by unique mineral and chemical compositions with atypically high growth rates, detrital contents, Fe/Mn ratios, and low Si/Al ratios, compared to deposits found elsewhere. High detritus reflects erosion of submarine outcrops and North America and Siberia cratons, transport by rivers and glaciers to the sea, and distribution by sea ice, brines, and currents. Uniquely high Fe/Mn ratios are attributed to expansive continental shelves, where diagenetic cycling releases Fe to bottom waters, and density flows transport shelf bottom water to the open Arctic Ocean. Low Mn contents reflect the lack of a mid‐water oxygen minimum zone that would act as a reservoir for dissolved Mn. The potential host phases and sources for elements with uniquely high contents are discussed with an emphasis on scandium. Scandium sorption onto Fe oxyhydroxides and Sc‐rich detritus account for atypically high scandium contents. The opening of Fram Strait in the Miocene and ventilation of the deep basins initiated Fe‐Mn crust growth ∼15 Myr ago.
Crustal Deformation in the India‐Eurasia Collision Zone From 25 Years of GPS Measurements
Authors: Zheng Gang , Wang Hua , Wright Tim J. , Lou Yidong , Zhang Rui , Zhang Weixing , Shi Chuang , Huang Jinfang , Wei Na
Published: September 2017

The India‐Eurasia collision zone is the largest deforming region on the planet; direct measurements of present‐day deformation from Global Positioning System (GPS) have the potential to discriminate between competing models of continental tectonics. But the increasing spatial resolution and accuracy of observations have only led to increasingly complex realizations of competing models. Here we present the most complete, accurate, and up‐to‐date velocity field for India‐Eurasia available, comprising 2576 velocities measured during 1991–2015. The core of our velocity field is from the Crustal Movement Observation Network of China‐I/II: 27 continuous stations observed since 1999; 56 campaign stations observed annually during 1998–2007; 1000 campaign stations observed in 1999, 2001, 2004, and 2007; 260 continuous stations operating since late 2010; and 2000 campaign stations observed in 2009, 2011, 2013, and 2015. We process these data and combine the solutions in a consistent reference frame with stations from the Global Strain Rate Model compilation, then invert for continuous velocity and strain rate fields. We update geodetic slip rates for the major faults (some vary along strike), and find that those along the major Tibetan strike‐slip faults are in good agreement with recent geological estimates. The velocity field shows several large undeforming areas, strain focused around some major faults, areas of diffuse strain, and dilation of the high plateau. We suggest that a new generation of dynamic models incorporating strength variations and strain‐weakening mechanisms is required to explain the key observations. Seismic hazard in much of the region is elevated, not just near the major faults.
Colliding Modons: A Nonlinear Test for the Evaluation of Global Dynamical Cores
Authors: Lin Shian‐Jiann , Harris Lucas , Chen Xi , Yao Weiye , Chai Junyi
Published: September 2017

The modon, a pair of counter‐rotating vortices propelling one another along a straight line, is an idealization of some observed large‐scale and small‐scale atmospheric and oceanic processes (e.g., twin cyclones), providing a challenging nonlinear test for fluid‐dynamics solvers (known as “dynamical cores”). We present an easy‐to‐setup test of colliding modons suitable for both shallow‐water and three‐dimensional dynamical cores on the sphere. Two pairs of idealized modons are configured to collide, exchange vortices, and depart in opposite directions, repeating indefinitely in the absence of ambient rotation. This test is applicable to both hydrostatic and nonhydrostatic dynamical cores and is particularly challenging for refined grids on the sphere, regardless of solution methodology, or vertical coordinate. We applied this test to three popular dynamical cores, used by three different general circulation models: the Spectral‐Element (SE) core of the Community Atmosphere Model, the Geophysical Fluid Dynamics Laboratory (GFDL) spectral core, and the GFDL Finite‐Volume Cubed‐Sphere dynamical core (FV3). Tests with a locally refined grid and nonhydrostatic dynamics were also performed with FV3. All cores tested were able to capture the propagation, collision, and exchange of the modons, albeit the rate at which the modon was diffused varied between the three cores and showed a strong dependence on the strength of hyperdiffusion.
How Well Do Rheumatology Fellows Manage Acute Infusion Reactions? A Pilot Curricular Intervention
Authors: Weiner Jason J. , Eudy Amanda M. , Criscione‐Schreiber Lisa G.
Published: September 2017

Objective

Infusible disease‐modifying antirheumatic drugs (DMARDs) are commonly prescribed in rheumatology and other fields. There are no published formal educational curricula that rheumatology fellowship programs can use to teach infusion reaction management skills to fellows. We aimed to better understand this educational gap and implement and assess the effectiveness of an experiential curriculum on acute infusion reaction management.

Methods

We included current rheumatology fellows and recent graduates from 5 fellowship programs. Using a novel behavioral checklist, we assessed fellows’ performance managing an infusion reaction in a simulation, followed by a didactic session focused on infusion reactions. Pre‐ and postsurveys assessed experiences to determine relevance, as well as attitudes and knowledge.

Results

Despite ubiquitous prescribing of infusible biologic DMARDs, >50% of fellows were uncomfortable managing infusion reactions. Only 11% of fellows reported infusion reaction training during fellowship, but 56% reported managing actual patient infusion reactions. In the simulated infusion reaction, fellows managed grade‐1 reactions appropriately, but grade‐4 reactions poorly, meeting <50% of objectives. All fellows discontinued the infusion in the setting of anaphylaxis, but only 56% administered epinephrine. There was no difference in performance or written knowledge by training year. All fellows felt more prepared to manage infusion reactions postcurriculum and were satisfied with the experience.

Conclusion

We confirmed an education gap in rheumatology fellowship training regarding infusion reactions, both in knowledge and performance. We developed and implemented a brief experiential curriculum including simulation of a high‐risk patient‐care scenario. This curriculum was well received and is easily exportable to other programs.
Active Fe‐Nx Sites in Carbon Nanosheets as Oxygen Reduction Electrocatalyst for Flexible All‐Solid‐State Zinc–Air Batteries
Authors: Wang Mengfan , Liu Sisi , Xu Na , Qian Tao , Yan Chenglin
Published: September 2017

Efficient electrocatalysts with accessible active sites are a hot topic due to their potential applications in commercial energy devices. Herein, the synthesis of a superior oxygen electrode catalyst is presented with active Fe‐Nx sites in carbon nanosheets, which exhibit prominent catalytic activity toward the oxygen reduction reaction. The high accessibility of Fe‐Nx sites is verified by cyanide treatment, and their activity decreases after coordinating with cyanide ions compared with catalysts containing particulate phase active sites. In aqueous zinc–air battery tests, primary batteries with the catalyst as the air electrode demonstrate superior power density and discharge stability. Impressively, flexible all‐solid‐state batteries using gel electrolytes are also assembled and can be used to light a light‐emitting‐diode bracelet, thus holding great potential for practical application in next‐generation electronic devices with portable and wearable characteristics.
Synthesis of Large Surface‐Area g‐C3N4 Comodified with MnOx and Au‐TiO2 as Efficient Visible‐Light Photocatalysts for Fuel Production
Authors: Raziq Fazal , Sun Liqun , Wang Yuying , Zhang Xuliang , Humayun Muhammad , Ali Sharafat , Bai Linlu , Qu Yang , Yu Haitao , Jing Liqiang
Published: September 2017

Herein, this study successfully fabricates porous g‐C3N4‐based nanocomposites by decorating sheet‐like nanostructured MnOx and subsequently coupling Au‐modified nanocrystalline TiO2. It is clearly demonstrated that the as‐prepared amount‐optimized nanocomposite exhibits exceptional visible‐light photocatalytic activities for CO2 conversion to CH4 and for H2 evolution, respectively by ≈28‐time (140 µmol g−1 h−1) and ≈31‐time (313 µmol g−1 h−1) enhancement compared to the widely accepted outstanding g‐C3N4 prepared with urea as the raw material, along with the calculated quantum efficiencies of ≈4.92% and 2.78% at 420 nm wavelength. It is confirmed mainly based on the steady‐state surface photovoltage spectra, transient‐state surface photovoltage responses, fluorescence spectra related to the produced •OH amount, and electrochemical reduction curves that the exceptional photoactivities are comprehensively attributed to the large surface area (85.5 m2 g−1) due to the porous structure, to the greatly enhanced charge separation and to the introduced catalytic functions to the carrier‐related redox reactions by decorating MnOx and coupling Au‐TiO2, respectively, to modulate holes and electrons. Moreover, it is suggested mainly based on the photocatalytic experiments of CO2 reduction with isotope 13CO2 and D2O that the produced •CO2 and •H as active radicals would be dominant to initiate the conversion of CO2 to CH4.
Mixed Metal Sulfides for Electrochemical Energy Storage and Conversion
Authors: Yu Xin Yao , (David) Lou Xiong Wen
Published: September 2017

Mixed metal sulfides (MMSs) have attracted increased attention as promising electrode materials for electrochemical energy storage and conversion systems including lithium‐ion batteries (LIBs), sodium‐ion batteries (SIBs), hybrid supercapacitors (HSCs), metal–air batteries (MABs), and water splitting. Compared with monometal sulfides, MMSs exhibit greatly enhanced electrochemical performance, which is largely originated from their higher electronic conductivity and richer redox reactions. In this review, recent progresses in the rational design and synthesis of diverse MMS‐based micro/nanostructures with controlled morphologies, sizes, and compositions for LIBs, SIBs, HSCs, MABs, and water splitting are summarized. In particular, nanostructuring, synthesis of nanocomposites with carbonaceous materials and fabrication of 3D MMS‐based electrodes are demonstrated to be three effective approaches for improving the electrochemical performance of MMS‐based electrode materials. Furthermore, some potential challenges as well as prospects are discussed to further advance the development of MMS‐based electrode materials for next‐generation electrochemical energy storage and conversion systems.
Characterization of liquid–liquid mass transfer performance in a capillary microreactor system
Authors: Li Guangxiao , Shang Minjing , Song Yang , Su Yuanhai
Published: September 2017

Liquid–liquid mass transfer performance in a capillary microreactor system was studied with an improved experimental method. Proper sampling modes were chosen to eliminate the effect of the sampling zone on the mass transfer characterization in capillary microreactor systems. The overall volumetric mass transfer coefficients in the T‐micromixer and the capillary microreactor system were found to smoothly increase and then significantly increase with increasing the Reynolds number of two immiscible liquid phases. Other factors such as the inlet mode and inner diameter of T‐micromixer, the capillary length, and the volumetric flux ratio of the aqueous phase to the organic phase affected the mass transfer performance in the T‐micromixer and the capillary microreactor system. Furthermore, the contribution of the mass transfer in the T‐micromixer zone to the capillary microreactor system was found to be in a range of 34–78% under the involved experimental conditions, which was emphasized in the proposed empirical correlations. © 2017 American Institute of Chemical Engineers AIChE J, 64: 1106–1116, 2018
Surface layer modification of AEMs by infiltration and photo‐cross‐linking to induce monovalent selectivity
Authors: Liu Huimin , Jiang Yuliang , Ding Jincheng , Shi Wenhui , Pan Jiefeng , Gao Congjie , Shen Jiangnan , van der Bruggen Bart
Published: September 2017

Surface modification of anion exchange membranes (AEMs) by attaching a negatively charged layer is the main method for preparing monovalent anion selective membranes. However, tremendous increase of membrane resistance and poor long‐term stability of the modified membranes face great challenges. In this work, a photosensitive molecule (4,4‐diazostilbene‐2,2‐disulfonic acid disodium salt [DAS]) was infiltrated into the membrane surface and immobilized in the structure by cross‐linking under UV irradiation. This method introduced negative charge to the surface layer of the AEMs without increasing membrane thickness, leading to high performance membrane with high monovalent anion selectivity. The optimized membrane (D‐5) shows the highest perm‐selectivity of 11.21, which is superior to the commercial selective membrane Selemion® ASV and previously reported monovalent anion selective AEMs. Furthermore, the newly developed membrane exhibits excellent long‐term stability, which can maintain constant selectivity during the 80 h ED experiment. © 2017 American Institute of Chemical Engineers AIChE J, 64: 993–1000, 2018
From clinical observations and molecular dissection to novel therapeutic strategies for primary immunodeficiency disorders
Authors: Ochs Hans D. , Petroni Daniel
Published: September 2017

The field of primary immunodeficiency diseases (PID) is rapidly expanding with more than 300 genetically defined disorders that have been clinically described and molecularly analyzed. The molecular dissection of these entities has led to the discovery of new immunologic pathways and to novel and effective disease‐specific therapies. This review provides a summary of these primary immune defects categorized by clinical phenotype and molecular similarity as defined by the International Union of Immunologic Societies (IUIS) Expert Committee for PID. In this synopsis, we discuss the molecular basis of various categories of PIDs including, but not limited to, severe combined immunodeficiencies, primary antibody deficiencies, immune dysregulation syndromes, as well as defects of the innate immune system such as phagocytic abnormalities, autoinflammatory fever syndromes, and complement deficiencies. We have attempted to focus on current strategies to prevent complications, ameliorate symptoms, or cure these disorders by promptly using antimicrobial therapies, immunoglobulin replacement, and hematopoietic stem cell transplantation. In addition, we will explore novel therapies such as molecularly targeted immunosuppression with monoclonal antibodies and specific immunomodulatory agents. Finally, we address experimental therapies targeting specific molecular defects, including gene therapy and gene editing.
Adsorption von hydrierten Protonen an der Luft‐Wasser‐Grenzfläche durch Orientierung
Authors: Mamatkulov Shavkat I. , Allolio Christoph , Netz Roland R. , Bonthuis Douwe Jan
Published: September 2017

Die Oberflächenspannung der Wasser‐Luft‐Grenzfläche steigt bei Zugabe von anorganischen Salzen, entsprechend einer Verarmung von Ionen. Hingegen verursachen die meisten Säuren eine Verringerung der Oberflächenspannung, was einen Überschuss von hydrierten Protonen an der Oberfläche anzeigt. Zusammen mit der scheinbar negativen Ladung der Grenzfläche zwischen Luft und reinem Wasser, die aus elektrokinetischen Experimenten folgt, führte diese experimentelle Beobachtung zu heftigen Diskussionen seit der Mitte des 19. Jahrhunderts. Hier bestimmen wir die Oberflächenspannung und Affinität der Ionen zur Oberfläche aus klassischen, thermodynamisch konsistenten Molekulardynamiksimulationen. Die Oberflächenspannungen der Lösungen mit NaOH, HCl und NaCl stimmen quantitativ bemerkenswert gut mit experimentell gemessenen Werten überein. Von den untersuchten Ionen wird nur H3O+ an der Luft‐Wasser‐Grenzfläche adsorbiert. Die Adsorption lässt sich durch den tiefen Potentialtopf erklären, der durch die Ausrichtung des H3O+‐Dipols im elektrischen Feld der Grenzfläche entsteht, was wir mit Ab‐initio‐Simulationen bestätigen.
Interlayer Bond Formation in Black Phosphorus at High Pressure
Authors: Scelta Demetrio , Baldassarre Adhara , Serrano‐Ruiz Manuel , Dziubek Kamil , Cairns Andrew B. , Peruzzini Maurizio , Bini Roberto , Ceppatelli Matteo
Published: September 2017

Black phosphorus was compressed at room temperature across the A17, A7 and simple‐cubic phases up to 30 GPa, using a diamond anvil cell and He as pressure transmitting medium. Synchrotron X‐ray diffraction showed the persistence of two previously unreported peaks related to the A7 structure in the pressure range of the simple‐cubic phase. The Rietveld refinement of the data demonstrates the occurrence of a two‐step mechanism for the A7 to simple‐cubic phase transition, indicating the existence of an intermediate pseudo simple‐cubic structure. From a chemical point of view this study represents a deep insight on the mechanism of interlayer bond formation during the transformation from the layered A7 to the non‐layered simple‐cubic phase of phosphorus, opening new perspectives for the design, synthesis and stabilization of phosphorene‐based systems. As superconductivity is concerned, a new experimental evidence to explain the anomalous pressure behavior of Tc in phosphorus below 30 GPa is provided.
An investigation on simultaneous effects of several parameters on the demulsification efficiency of various crude oils
Authors: Farrokhi Fatemeh , Jafari Nasr Mohammad Reza , Rahimpour Mohammad Reza , Arjmand Mehdi , Vaziri Seyed Ali
Published: September 2017

The current study aims to investigate the simultaneous effects of a novel magnetic demulsifier concentration as well as operating temperature on the demulsification efficiency of three different aboriginal samples of Persian Gulf, namely, light, medium, and heavy crudes. In this regard, TOMAC‐Fe3O4‐SiO2 (MT) was chosen as the magnetic nano‐modified demulsifier. The optimum concentrations of MT were obtained to be 0.98, 0.99, and 1.1 ppm, while the optimum operating temperatures determined were 38.2, 45.2, and 50.1 °C, corresponding to a demulsification efficiency of 95%, 88%, and 81% at the optimum temperature and optimum concentration of MT for light, medium, and heavy crude oil, respectively. Finally, using the obtained experimental data, empirical correlations were proposed for the first time to correlate the nano‐modified demulsifier concentration and operating temperature to the demulsification efficiency for the three studied types of crude oil with different American Petroleum Institute degrees. © 2017 Curtin University and John Wiley & Sons, Ltd.
One‐Pot Green Synthesis of Nitrogen‐Doped Carbon Quantum Dots for Cell Nucleus Labeling and Copper(II) Detection
Authors: Ci Jiliang , Tian Ye , Kuga Shigenori , Niu Zhongwei , Wu Min , Huang Yong
Published: September 2017

The doping of nitrogen into carbon quantum dots is vitally important for improved fluorescence performance. However, the synthesis of nitrogen‐doped carbon quantum dots (N‐CQDs) is usually conducted under strong acid and high temperature, which results in environmental pollution and energy consumption. Herein, the N‐CQDs were prepared by a mild one‐pot hydrothermal process. The hydrothermal reaction temperature was adjusted to control the particle size, nitrogen/carbon atomic ratio, and quantum yield. The products were water soluble with a narrow particle size distribution and good dispersion stability over a wide pH range. The N‐CQDs could penetrate into the HeLa cell nucleus without any further functionalization. Moreover, the fluorescence of N‐CQDs could be selectively quenched by Cu2+, which suggested applications for the detection of Cu2+ in human plasma.
ADNP Plays a Key Role in Autophagy: From Autism to Schizophrenia and Alzheimer's Disease
Authors: Sragovich Shlomo , Merenlender‐Wagner Avia , Gozes Illana
Published: September 2017

Activity‐dependent neuroprotective protein (ADNP), discovered in our laboratory in 1999, has been characterized as a master gene vital for mammalian brain formation. ADNP de novo mutations in humans result in a syndromic form of autism‐like spectrum disorder (ASD), including cognitive and motor deficits, the ADNP syndrome (Helsmoortel‐Van Der Aa). One of the most important cellular processes associated with ADNP is the autophagy pathway, recently discovered by us as a key player in the pathophysiology of schizophrenia. In this regard, given the link between the microtubule and autophagy systems, the ADNP microtubule end binding protein motif, namely, the neuroprotective NAP (NAPVSIPQ), was found to enhance autophagy while protecting microtubules and augmenting ADNP's association with both systems. Thus, linking autophagy and ADNP is proposed as a major target for intervention in brain diseases from autism to Alzheimer's disease (AD) and our findings introduce autophagy as a possible novel target for treating schizophrenia.
Cell Polarity and Notch Signaling: Linked by the E3 Ubiquitin Ligase Neuralized?
Authors: Perez‐Mockus Gantas , Schweisguth Francois
Published: September 2017

Notch is a mechanosensitive receptor that requires direct cell–cell contact for its activation. Both the strength and the range of notch signaling depend on the size and geometry of the contact sites between cells. These properties of cell–cell contacts in turn depend on cell shape and polarity. At the molecular level, the E3 ubiquitin ligase Neuralized (Neur) links receptor activation with epithelial cell remodeling. Neur regulates the endocytosis of the Notch ligand Delta (Dl), hence Notch activation. It also targets the apical polarity protein Stardust (Sdt) to promote the endocytosis of the Crumbs complex, thereby contributing to epithelium remodeling. Here, we review the interplay between Notch signaling and cell polarity and discuss the possible significance of linking Notch signaling with epithelial cell polarity via a common regulator.
Effect of socioeconomic status on stage at diagnosis of lung cancer in a hospital‐based multicenter retrospective clinical epidemiological study in China, 2005–2014
Authors: Li Yuanqiu , Shi Jufang , Yu Shicheng , Wang Le , Liu Jianjun , Ren Jiansong , Gao Shugeng , Hui Zhouguang , Li Junling , Wu Ning , Yang Boyan , Liu Shangmei , Qin Mingfang , Wang Debin , Liao Xianzhen , Xing Xiaojing , Du Lingbin , Yang Li , Liu Yuqin , Zhang Yongzhen , Zhang Kai , Qiao Youlin , He Jie , Dai Min , Yao Hongyan ,   the Health Economic Evaluation Working Group, Cancer Screening Program in Urban China (CanSPUC)
Published: September 2017

There is inconsistent evidence of associations between socioeconomic status (SES) and lung cancer stage in non‐Chinese populations up to now. We set out to determine how SES affects stage at diagnosis at both individual and area levels, from a hospital‐based multicenter 10‐year (2005–2014) retrospective clinical epidemiological study of 7184 primary lung cancer patients in mainland China. Individual‐level SES data were measured based on two indicators from case report forms of the study: an individual's education and occupation. Seven census indicator variables were used as surrogates for the area‐level SES with principal component analysis (PCA). Multivariate analysis was undertaken using binary logistic regressions and multinomial logit model to describe the association and explore the effect across tertiles on stage after adjusting for demographic variables. There was a significant stepwise gradient of effect across different stages in the highest tertile of area‐level SES, comparing with the lowest tertile of area‐level SES (ORs, 0.77, 0.67, and 0.29 for stage II, III, and IV). Patients with higher education were less likely to have stage IV lung cancer, comparing with the illiterate group (ORs, 0.52, 0.63, 0.71, 0.64 for primary school, middle school, high school, college degree or above subgroup, respectively). Findings suggest that the most socioeconomically deprived areas may be associated with a higher risk of advanced‐stage lung cancer, and increasing educational level may be correlated with a lower risk to be diagnosed at advanced stage in both men and women.
Evaluation of a prediction model for colorectal cancer: retrospective analysis of 2.5 million patient records
Authors: Birks Jacqueline , Bankhead Clare , Holt Tim A. , Fuller Alice , Patnick Julietta
Published: September 2017

Earlier detection of colorectal cancer greatly improves prognosis, largely through surgical excision of neoplastic polyps. These include benign adenomas which can transform over time to malignant adenocarcinomas. This progression may be associated with changes in full blood count indices. An existing risk algorithm derived in Israel stratifies individuals according to colorectal cancer risk using full blood count data, but has not been validated in the UK. We undertook a retrospective analysis using the Clinical Practice Research Datalink. Patients aged over 40 with full blood count data were risk‐stratified and followed up for a diagnosis of colorectal cancer over a range of time intervals. The primary outcome was the area under the receiver operating characteristic curve for the 18–24‐month interval. We also undertook a case–control analysis (matching for age, sex, and year of risk score), and a cohort study of patients undergoing full blood count testing during 2012, to estimate predictive values. We included 2,550,119 patients. The area under the curve for the 18–24‐month interval was 0.776 [95% confidence interval (CI): 0.771, 0.781]. Performance improves as the time interval reduces. The area under the curve for the age‐matched case–control analysis was 0.583 [0.574, 0.591]. For the population risk‐scored in 2012, the positive predictive value at 99.5% specificity was 8.8% with negative predictive value 99.6%. The algorithm offers an additional means of identifying risk of colorectal cancer, and could support other approaches to early detection, including screening and active case finding.
Nonsteroidal anti‐inflammatory drugs (NSAIDs) and prostate cancer risk: results from the EPICAP study
Authors: Doat Solene , Cénée Sylvie , Trétarre Brigitte , Rebillard Xavier , Lamy Pierre‐Jean , Bringer Jean‐Pierre , Iborra François , Murez Thibaut , Sanchez Marie , Menegaux Florence
Published: September 2017

Chronic inflammation may play a role in prostate cancer carcinogenesis. In that context, our objective was to investigate the role of nonsteroidal anti‐inflammatory drugs (NSAIDs) in prostate cancer risk based on the EPICAP data. EPICAP is a population‐based case–control study carried out in 2012–2013 (département of Hérault, France) that enrolled 819 men aged less than 75 years old newly diagnosed for prostate cancer and 879 controls frequency matched to the cases on age. Face to face interviews gathered information on several potential risk factors including NSAIDs use. Odds ratios (ORs) and their 95% confidence intervals (CIs) were calculated using unconditional logistic regression models. All‐NSAIDs use was inversely associated with prostate cancer: OR 0.77, 95% CI 0.61–0.98, especially in men using NSAIDs that preferentially inhibit COX‐2 activity (OR 0.48, 95% CI 0.28–0.79). Nonaspirin NSAIDs users had a decreased risk of prostate cancer (OR 0.72, 95% CI 0.53–0.99), particularly among men with an aggressive prostate cancer (OR 0.49, 95% CI 0.27–0.89) and in men with a personal history of prostatitis (OR 0.21, 95% CI 0.07–0.59). Our results are in favor of a decreased risk of prostate cancer in men using NSAIDs, particularly for men using preferential anti‐COX‐2 activity. The protective effect of NSAIDs seems to be more pronounced in aggressive prostate cancer and in men with a personal history of prostatitis, but this needs further investigations to be confirmed.
Anti‐Coke Properties of Acid‐Treated Bentonite‐Supported Nickel‐Boron Catalyst
Authors: Jiang Yuexiu , Huang Tongxia , Xu Yun , Li Xiliang , Qin Zuzeng , Ji Hongbing
Published: September 2017

Boron was introduced into nickel/acid‐treated bentonite (Ni/A‐Bn) catalysts to improve the anti‐coking ability of the nickel‐based catalyst in the hydrogenation of nitrobenzene. The results showed the B‐doped Ni/A‐Bn catalyst was more active than that without B. During an extended reaction period, Ni‐B/acid‐treated bentonite (Ni‐B/A‐Bn) resulted in a high nitrobenzene conversion and a high aniline selectivity. The lifetime of Ni‐B/A‐Bn was extended significantly compared with that of Ni/A‐Bn. The addition of B into Ni/A‐Bn decreased the NiO particle size, improved the dispersion of active components, and decreased carbon deposition. The combination of B and Ni prevented coke deposition on metallic Ni during nitrobenzene hydrogenation, which reduced carbon deposition on the surface of Ni‐B/A‐Bn.
1‐Alkali‐metal‐2‐alkyl‐1,2‐dihydropyridines: Soluble Hydride Surrogates for Catalytic Dehydrogenative Coupling and Hydroboration Applications
Authors: McLellan Ross , Kennedy Alan R. , Mulvey Robert E. , Orr Samantha A. , Robertson Stuart D.
Published: September 2017

Equipped with excellent hydrocarbon solubility, the lithium hydride surrogate 1‐lithium‐2‐tert‐butyl‐1,2‐dihydropyridine (1tLi) functions as a precatalyst to convert Me2NH⋅BH3 to [NMe2BH2]2 (89 % conversion) under competitive conditions (2.5 mol %, 60 h, 80 °C, toluene solvent) to that of previously reported LiN(SiMe3)2. Sodium and potassium dihydropyridine congeners produce similar high yields of [NMe2BH2]2 but require longer times. Switching the solvent to pyridine induces a remarkable change in the dehydrocoupling product ratio, with (NMe2)2BH favoured over [NMe2BH2]2 (e.g., 94 %:2 % for 1tLi). Demonstrating its versatility, precatalyst 1tLi was also successful in promoting hydroboration reactions between pinacolborane and a selection of aldehydes and ketones. Most reactions gave near quantitative conversion to the hydroborated products in 15 minutes, though sterically demanding carbonyl substrates require longer times. The mechanisms of these rare examples of Group 1 metal‐catalysed processes are discussed.
One‐Dimensional Phosphorus Nanostructures: from Nanorings to Nanohelices
Authors: Sansone Giuseppe , Maschio Lorenzo , Karttunen Antti J.
Published: September 2017

Phosphorus nanorings and nanohelices—speculated to exist over 20 years ago—have been systematically derived from one parent structure and studied with quantum chemical methods. The (P8P2)n nanorings have been recently synthetized inside carbon nanotube templates, and our comprehensive analysis of possible structural arrangements strongly supports the possibility to experimentally determine the closely related (P8P2)n nanohelices. The nanohelices possess very low stiffness, suggesting interesting mechanical properties with nano‐spring‐like behavior.
Twice weekly pulse and daily continuous‐dose erlotinib as initial treatment for patients with epidermal growth factor receptor–mutant lung cancers and brain metastases
Authors: Arbour Kathryn C. , Kris Mark G. , Riely Gregory J. , Ni Ai , Beal Kathryn , Daras Mariza , Hayes Sara A. , Young Robert J. , Rodriguez Christopher R. , Ahn Linda , Pao William , Yu Helena A.
Published: September 2017

BACKGROUND

In a phase 1 study of pulse/continuous‐dose erlotinib, no patient had disease progression in the central nervous system (CNS). This expansion cohort of the phase 1 study tested the same regimen in a cohort of individuals with epidermal growth factor receptor (EGFR)–mutant lung cancers with untreated brain metastases.

METHODS

Patients had not received EGFR tyrosine kinase inhibitors or radiation for brain metastases. All received 1200 mg of erlotinib on days 1 and 2 and 50 mg on days 3 to 7 weekly. The primary endpoints were the overall and CNS response rates (according to version 1.1 of the Response Evaluation Criteria in Solid Tumors).

RESULTS

Between May 2015 and August 2016, 19 patients were enrolled. Forty‐two percent of the patients had target brain lesions, and the median size of the target brain lesions was 13 mm. Overall, 14 patients (74%; 95% confidence interval [CI], 51%‐89%) had partial responses. The response rate in brain metastases was 75%. The overall median progression‐free survival was 10 months (95% CI, 7 months to not reached). Only 3 patients (16%) had CNS progression. To date, 4 patients required CNS radiation at some time during their course. The adverse events (any grade) seen in 10% or more of the patients were rash, diarrhea, nausea, an increase in alanine aminotransferase, and fatigue.

CONCLUSIONS

Pulse/continuous‐dose erlotinib produced a 74% overall response rate and a 75% response rate in brain metastases in patients with EGFR‐mutant lung cancers and untreated brain metastases. CNS control persisted even after progression elsewhere. Although this regimen did not improve progression‐free survival or delay the emergence of EGFR T790M, it prevented progression in the brain and could be useful in situations in which CNS control is critical. Cancer 2018;124:105‐9. © 2017 American Cancer Society.
Pharmacokinetics, Safety, and Tolerability of Vortioxetine Following Single‐ and Multiple‐Dose Administration in Healthy Japanese Adults
Authors: Matsuno Kumi , Nakamura Koki , Aritomi Yutaka , Nishimura Akira
Published: September 2017

Three phase 1 randomized single‐center studies assessed the pharmacokinetics, safety, and tolerability of vortioxetine after single‐ and multiple‐dose administration in healthy Japanese adults. Study 1 assessed the pharmacokinetics of vortioxetine after administration of single rising doses to men and multiple doses to men and women; study 2 evaluated vortioxetine pharmacokinetics in elderly adults; and study 3 assessed food effects on vortioxetine pharmacokinetics in healthy men. The primary end points included pharmacokinetic parameters of vortioxetine and incidence of adverse events (AEs). Across all studies, 130 participants were randomized and 128 participants completed the studies. Vortioxetine was absorbed and eliminated from plasma slowly, and exposure to vortioxetine increased in an almost dose‐proportional manner. No clinically significant differences in the pharmacokinetics of vortioxetine or its metabolites were observed between the sexes in young and elderly adults. Study 3 demonstrated that vortioxetine and its metabolites had similar pharmacokinetics when administered in the fasted and fed states. Importantly, vortioxetine was safe and tolerated, with incidence of AEs comparable to that of placebo. No deaths or serious AEs leading to trial discontinuation were observed. Overall, vortioxetine pharmacokinetics, safety, and tolerability in Japanese adults were comparable to reports in non‐Japanese populations.
LY2963016 Insulin Glargine and Insulin Glargine (Lantus) Produce Comparable Pharmacokinetics and Pharmacodynamics at Two Dose Levels
Authors: Zhang Xin , Lam Eric Chen Quin , Seger Mary E. , Coutant David , Chua Laiyi , Tan Lai Hock , Soon Danny , Linnebjerg Helle
Published: September 2017

LY2963016 (LY IGlar) and Lantus (IGlar) are insulin glargine products with identical amino acid sequences. This was a phase 1 single‐site, randomized, subject‐ and investigator‐blinded, 4‐treatment, 4‐period crossover study to compare the pharmacokinetic (PK) and pharmacodynamic (PD) properties of LY IGlar and IGlar at 2 different doses. Fasted healthy subjects were randomly assigned to receive 2 single doses of LY IGlar and IGlar (0.3 and 0.6 U/kg for each product). Blood samples were collected up to 24 hours postdose to assess PK, and a euglycemic clamp lasting up to 24 hours postdose was conducted to assess PD. Twenty‐four healthy subjects aged 23 to 52 years participated in the study. The primary PK parameters (area under the concentration versus time curve from 0 to 24 hours [AUC0–24] and maximum observed drug concentration [Cmax]) and PD parameters (total amount of glucose infused during the clamp [Gtot] and maximum glucose infusion rate [Rmax]) were not statistically different between LY IGlar and IGlar at either dose. No safety concerns were noted with either drug. The study demonstrated that the PK and PD parameters for LY IGlar and IGlar were comparable following single doses at both 0.3 and 0.6 U/kg.
Reactive Electrophilic OI− Species Evidenced in High‐Performance Iridium Oxohydroxide Water Oxidation Electrocatalysts
Authors: Massué Cyriac , Pfeifer Verena , van Gastel Maurice , Noack Johannes , Algara‐Siller Gerardo , Cap Sébastien , Schlögl Robert
Published: September 2017

Although quasi‐amorphous iridium oxohydroxides have been identified repeatedly as superior electrocatalysts for the oxygen evolution reaction (OER), an exact description of the performance‐relevant species has remained a challenge. In this context, we report the characterization of hydrothermally prepared iridium(III/IV) oxohydroxides that exhibit exceptional OER performances. Holes in the O 2p states of the iridium(III/IV) oxohydroxides result in reactive OI− species, which are identified by characteristic near‐edge X‐ray absorption fine structure (NEXAFS) features. A prototypical titration reaction with CO as a probe molecule shows that these OI− species are highly susceptible to nucleophilic attack at room temperature. Similarly to the preactivated oxygen involved in the biological OER in photosystem II, the electrophilic OI− species evidenced in the iridium(III/IV) oxohydroxides are suggested to be precursors to species involved in the O−O bond formation during the electrocatalytic OER. The CO titration also highlights a link between the OER performance and the surface/subsurface mobility of the OI− species. Thus, the superior electrocatalytic properties of the iridium (III/IV) oxohydroxides are explained by their ability to accommodate preactivated electrophilic OI− species that can migrate within the lattice.
Increased grassland arthropod production with mammalian herbivory and eutrophication: a test of mediation pathways
Authors: Lind Eric M. , La Pierre Kimberly J. , Seabloom Eric W. , Alberti Juan , Iribarne Oscar , Firn Jennifer , Gruner Daniel S. , Kay Adam D. , Pascal Jesus , Wright Justin P. , Yang Louie , Borer Elizabeth T.
Published: September 2017

Increases in nutrient availability and alterations to mammalian herbivore communities are a hallmark of the Anthropocene, with consequences for the primary producer communities in many ecosystems. While progress has advanced understanding of plant community responses to these perturbations, the consequences for energy flow to higher trophic levels in the form of secondary production are less well understood. We quantified arthropod biomass after manipulating soil nutrient availability and wild mammalian herbivory, using identical methods across 13 temperate grasslands. Of experimental increases in nitrogen, phosphorus, and potassium, only treatments including nitrogen resulted in significantly increased arthropod biomass. Wild mammalian herbivore removal had a marginal, negative effect on arthropod biomass, with no interaction with nutrient availability. Path analysis including all sites implicated nutrient content of the primary producers as a driver of increased arthropod mean size, which we confirmed using 10 sites for which we had foliar nutrient data. Plant biomass and physical structure mediated the increase in arthropod abundance, while the nitrogen treatments accounted for additional variation not explained by our measured plant variables. The mean size of arthropod individuals was 2.5 times more influential on the plot‐level total arthropod biomass than was the number of individuals. The eutrophication of grasslands through human activity, especially nitrogen deposition, thus may contribute to higher production of arthropod consumers through increases in nutrient availability across trophic levels.
Synthesis of Highly Functionalized Pyrrolidine Derivatives from Easily Accessible Diethyl (E)‐4‐Oxohex‐2‐enedioate
Authors: Kumar Thota Ganesh , Tamilarasan Duraiyarasu , Balamurugan Rengarajan
Published: September 2017

The diastereoselective synthesis of highly substituted pyrrolidines has been accomplished using a six‐carbon building block bearing carbon atoms with different reactivities. In this reaction, the building block acts a 1,3‐dipole and undergoes cyclization with imines formed in situ to give pyrrolidine derivatives.
Classification of in vitro genotoxicants using a novel multiplexed biomarker assay compared to the flow cytometric micronucleus test
Authors: Wilde Sabrina , Dambowsky Miriam , Hempt Claudia , Sutter Andreas , Queisser Nina
Published: September 2017

Regulatory in vitro genotoxicity testing exhibits shortcomings in specificity and mode of action (MoA) information. Thus, the aim of this work was to evaluate the performance of the novel MultiFlow® assay composed of mechanistic biomarkers quantified in TK6 cells after treatment (4 and 24 hr): γH2AX (DNA double strand breaks), phosphorylated H3 (mitotic cells), translocated p53 (genotoxicity), and cleaved PARP1 (apoptosis). A reference dataset of 31 compounds with well‐established MoA was studied using the MicroFlow® micronucleus assay. A positive call was raised following the earlier published criteria from Litron Laboratories. In the light of our data, these evaluation criteria should probably be adjusted since only 8/11 (73%) nongenotoxicants and 18/20 (90%) genotoxicants were correctly identified. Moreover, there is a need for new in vitro tools to delineate the predominant MoA as in the MicroFlow® assay only 5/9 (56%) aneugens and 4/11 (36%) clastogens were correctly classified. In contrast, the MultiFlow® assay provides more in‐depth information about the MoA and therefore reliably discriminates clastogens, aneugens, and nongenotoxicants. By using a lab‐specific, practical threshold for the aforementioned biomarkers, 10/11 (91%) nongenotoxicants and 19/20 genotoxicants (95%), 9/11 (82%) clastogens, and 8/9 (89%) aneugens were correctly categorized, suggesting a clear improvement over the MicroFlow®. Furthermore, the MultiFlow markers were benchmarked against established methods to assess the validity of the data. Altogether, these findings demonstrated good agreement between the MultiFlow® assay and the benchmarking methods. Finally, p21 may improve class discrimination given the correct identification of 4/4 (100%) aneugens and 2/5 (40%) clastogens. Environ. Mol. Mutagen. 58:662–677, 2017. © 2017 Wiley Periodicals, Inc.
New Energy and Weather Services in the Context of the Energy Transition
Authors: Ciriminna Rosaria , Albanese Lorenzo , Meneguzzo Francesco , Pagliaro Mario
Published: September 2017

The potential of weather forecasting is increasingly being exploited by power generators and transmission‐system operators as renewable electricity generation has become a significant and increasing part of the energy mix in many countries. Showing how the forecasts are interpreted and actually used, we suggest avenues for policy makers on how best utilizing meteorology in the unfolding energy transition through new, integrated meteorology and energy services.
CO2 adsorption and desorption performance of waste ion‐exchange resin‐based activated carbon
Authors: Wei Mengqi , Yu Qingbo , Duan Wenjun , Zuo Zongliang , Hou Limin , Dai Jinjie
Published: September 2017

Activated carbons were produced using waste ion‐exchange resin, and the effects of different activation temperatures were researched in this article. The experimental results indicate that the activated carbons are microporous carbons. The BET specific surface area and total volume increase at first and then decrease as the activation temperature increases. The maximum adsorption capacity is 81.24 mg/g at 30°C. A higher adsorption temperature and lower CO2 partial pressure resulted in a lower CO2 adsorption capacity. After 20 adsorption–desorption cycles, the CO2 adsorption capacity decreases slightly, and the regeneration degree is always at a high level, which indicates that the activated carbons can be used for a long time. The results in this work suggest that waste ion‐exchange resin‐based activated carbons show great potential as adsorbents for postcombustion CO2 capture. © 2017 American Institute of Chemical Engineers Environ Prog, 37: 703–711, 2018