bluuebunny/crossref_metadata_2025 huggingface dataset:
High‐Performance Sodium Metal Anodes Enabled by a Bifunctional Potassium Salt
Authors: Shi Qiuwei , Zhong Yiren , Wu Min , Wang Hongzhi , Wang Hailiang
Published: April 2018

Developing Na metal anodes that can be deeply cycled with high efficiency for a long time is a prerequisite for rechargeable Na metal batteries to be practically useful despite their notable advantages in theoretical energy density and potential low cost. Their high chemical reactivity with the electrolyte and tendency for dendrite formation are two major issues limiting the reversibility of Na metal electrodes. In this work, we introduce for the first time potassium bis(trifluoromethylsulfonyl)imide (KTFSI) as a bifunctional electrolyte additive to stabilize Na metal electrodes, in which the TFSI− anions decompose into lithium nitride and oxynitrides to render a desirable solid electrolyte interphase layer while the K+ cations preferentially adsorb onto Na protrusions and provide electrostatic shielding to suppress dendritic deposition. Through the cooperation of the cations and anions, we have realized Na metal electrodes that can be deeply cycled at a capacity of 10 mAh cm−2 for hundreds of hours.
Intermolecular σ‐Bond Cross‐Exchange Reaction between Cyclopropenones and (Benzo)silacyclobutanes: Straightforward Access towards Sila(benzo)cycloheptenones
Authors: Zhao Wen‐Tao , Gao Fang , Zhao Dongbing
Published: April 2018

Described herein is the first intermolecular σ‐bond exchange reaction between the C−C bond of cyclopropenones and C−Si bond of (benzo)silacyclobutanes and it proceeds smoothly by treatment with either 1 mol % of a palladium or 2 mol % of a nickel catalyst. This reaction constitutes an unprecedented route for the synthesis of various sila(benzo)suberones. And it is also the first example of a σ‐bond exchange reaction involving cyclopropenones.
Schwere Carbenhomologe: donorfreie Bismutenium‐ und Stibenium‐Ionen
Authors: Olaru Marian , Duvinage Daniel , Lork Enno , Mebs Stefan , Beckmann Jens
Published: April 2018

Kinetisch stabilisierte Kongenere von Carbenen, R2C, die sechs Valenzelektronen aufweisen (vier bindende und zwei nicht‐bindende Elektronen) waren bisher auf die Elemente der 14. Gruppe, R2E (E=Si, Ge, Sn, Pb; R=Alkyl oder Aryl), beschränkt, während die isoelektronischen Kationen der 15. Gruppe, zweiwertige Spezies des Typs [R2E]+(E=P, As, Sb, Bi; R=Alkyl oder Aryl), unbekannt waren. Hier wird über die ersten beiden Vertreter berichtet: das Bismutenium‐Ion [(2,6‐Mes2C6H3)2Bi][BArF4] (1, Mes=2,4,6‐Me3C6H2, ArF=3,5‐(CF3)2C6H3) und das Stibenium‐Ion [(2,6‐Mes2C6H3)2Sb][B(C6F5)4] (2), die durch den kombinierten Einsatz von sterisch anspruchvollen meta‐Terphenyl‐Substituenten und schwach koordinierenden Anionen erhalten wurden.
Oxygen Vacancies in ZnO Nanosheets Enhance CO2 Electrochemical Reduction to CO
Authors: Geng Zhigang , Kong Xiangdong , Chen Weiwei , Su Hongyang , Liu Yan , Cai Fan , Wang Guoxiong , Zeng Jie
Published: April 2018

As electron transfer to CO2 is generally considered to be the critical step during the activation of CO2, it is important to develop approaches to engineer the electronic properties of catalysts to improve their performance in CO2 electrochemical reduction. Herein, we developed an efficient strategy to facilitate CO2 activation by introducing oxygen vacancies into electrocatalysts with electronic‐rich surface. ZnO nanosheets rich in oxygen vacancies exhibited a current density of −16.1 mA cm−2 with a Faradaic efficiency of 83 % for CO production. Based on density functional theory (DFT) calculations, the introduction of oxygen vacancies increased the charge density of ZnO around the valence band maximum, resulting in the enhanced activation of CO2. Mechanistic studies further revealed that the enhancement of CO production by introducing oxygen vacancies into ZnO nanosheets originated from the increased binding strength of CO2 and the eased CO2 activation.
Shell‐Isolated Tip‐Enhanced Raman and Fluorescence Spectroscopy
Authors: Huang Ya‐Ping , Huang Sheng‐Chao , Wang Xiang‐Jie , Bodappa Nataraju , Li Chao‐Yu , Yin Hao , Su Hai‐Sheng , Meng Meng , Zhang Hua , Ren Bin , Yang Zhi‐Lin , Zenobi Renato , Tian Zhong‐Qun , Li Jian‐Feng
Published: April 2018

Tip‐enhanced Raman spectroscopy can provide molecular fingerprint information with ultrahigh spatial resolution, but the tip will be easily contaminated, thus leading to artifacts. It also remains a great challenge to establish tip‐enhanced fluorescence because of the quenching resulting from the proximity of the metal tip. Herein, we report shell‐isolated tip‐enhanced Raman and fluorescence spectroscopies by employing ultrathin shell‐isolated tips fabricated by atomic layer deposition. Such shell‐isolated tips not only show outstanding electromagnetic field enhancement in TERS but also exclude interference by contaminants, thus greatly promoting applications in solution. Tip‐enhanced fluorescence has also been achieved using these shell‐isolated tips, with enhancement factors of up to 1.7×103, consistent with theoretical simulations. Furthermore, tip‐enhanced Raman and fluorescence signals are acquired simultaneously, and their relative intensities can be manipulated by changing the shell thickness. This work opens a new avenue for ultrahigh resolution surface analysis using plasmon‐enhanced spectroscopies.
Divergent Total Syntheses of Enmein‐Type Natural Products: (−)‐Enmein, (−)‐Isodocarpin, and (−)‐Sculponin R
Authors: Pan Saiyong , Chen Sicong , Dong Guangbin
Published: April 2018

Divergent total syntheses of the enmein‐type natural products (−)‐enmein, (−)‐isodocarpin, and (−)‐sculponin R have been achieved in a concise fashion. Key features of the strategy include 1) an efficient early‐stage cage formation to control succeeding diastereoselectivity, 2) a one‐pot acylation/akylation/lactonization to construct the C‐ring and C8 quarternary center, 3) a reductive alkenylation approach to construct the enmain D/E rings and 4) a flexible route to allow divergent syntheses of three natural products.
Design, synthesis, and biological evaluation of 2‐substituted‐2,3,4,9‐tetrahydrospiro‐β‐carboline‐3‐carboxylic acid derivatives as first‐in‐class mast cell stabilizers
Authors: Singh Jatinder , Shah Ramanpreet , Singh Dhandeep , Jaggi Amteshwar S. , Singh Nirmal
Published: April 2018

Mast cell degranulation plays a momentous role in myriad diseases like asthma, eczema, allergic rhinitis, and conjunctivitis as well as anaphylactic shock; hence, there is an unmet need for developing new mast cells stabilizers. The reported mast cell stabilizers have a heterocyclic moiety and an acidic group. Furthermore, the role of tryptophan in suppression of mast cell activation is established. Hence, we prepared constrained analogs of tryptophan, which are derivatives of 2,3,4,9‐tetrahydrospiro‐β‐carboline‐3‐carboxylic acid, and evaluated them forex vivoinhibition of compound 48/80‐induced mast degranulation activity. By comparing IC50(μM) values with that of the standard drug sodium cromoglycate (IC50 = 0.489 ± 0.003 μM), compounds with bulky groups like heptyl (compound9; IC50 = 0.389 ± 0.015 μM) and octyl (compound10; IC50 = 0.354 ± 0.023 μM) were found to be of similar potency as sodium cromoglycate. Furthermore, the polar group‐containing compounds like the chloropropyl (compound16; IC50 = 0.382 ± 0.083 μM) and benzoyl derivative (compound14; IC50 = 00.469 ± 0.032 μM) were also found to be of similar potency as sodium cromoglycate. This is a seminal study of spiro‐β‐carboline mast cell stabilization having a wider scope in mast cell research; yet, the mechanism of action remains elusive.
Long‐Term Outcomes Following Achievement of Clinically Inactive Disease in Juvenile Idiopathic Arthritis
Authors: Shoop‐Worrall Stephanie J. W. , Verstappen Suzanne M. M. , McDonagh Janet E. , Baildam Eileen , Chieng Alice , Davidson Joyce , Foster Helen , Ioannou Yiannis , McErlane Flora , Wedderburn Lucy R. , Thomson W. , Hyrich Kimme L.
Published: April 2018

Objective

Potential targets for treat‐to‐target strategies in juvenile idiopathic arthritis are minimal disease activity (MDA) and clinically inactive disease (CID). We undertook this study to compare short‐ and long‐term outcomes following achievement of MDA and CID on the 10‐joint clinical Juvenile Arthritis Disease Activity Score (cJADAS10) and following achievement of CID on Wallace et al's preliminary criteria.

Methods

Children recruited to the Childhood Arthritis Prospective Study, a UK multicenter inception cohort, were selected if they were recruited prior to January 2011 and diagnosed as having oligoarthritis or rheumatoid factor–negative or –positive polyarthritis. One year following diagnosis, children were assessed for MDA on the cJADAS10 and for CID on both Wallace et al's preliminary criteria and the cJADAS10. Associations were tested between those disease states and functional ability, absence of joints with limited range of motion, psychosocial health, and pain at 1 year and annually to 5 years.

Results

Of 832 children, 70% were female and the majority had oligoarthritis (68%). At 1 year, 21% had achieved CID according to both definitions, 7% according to Wallace et al's preliminary criteria alone, and 16% according to the cJADAS10 alone; 56% had not achieved CID. Only 10% of children in the entire cohort achieved MDA without also achieving CID. Achieving either early CID state was associated with a greater absence of joints with limited range of motion. However, only CID according to the cJADAS10 was associated with improved functional ability and psychosocial health. Achieving CID was superior to achieving MDA in terms of short‐ and long‐term pain and the absence of joints with limited range of motion.

Conclusion

CID on the cJADAS10 may be preferable as a treatment target to CID on Wallace et al's preliminary criteria in terms of both feasibility of application and long‐term outcomes.
Monitoringgestützte Analyse von Schwingungsdämpfern in Turmbauwerken
Authors: Dragos Kosmas , Steiner Maria , Zabel Volkmar , Smarsly Kay
Published: April 2018

Schlanke Bauwerke, wie Türme und Masten, zeigen oft ein unerwünschtes dynamisches Verhalten, wenn sie zeitlich veränderlichen Belastungen ausgesetzt sind. Eigenschwingungen höherer Ordnung sowie Resonanzphänomene zwischen den einwirkenden dynamischen Lasten und der Struktur können zu beträchtlichen Bauwerksschwingungen führen. Zur Reduzierung solcher Schwingungen werden häufig Schwingungsdämpfersysteme eingesetzt. Ein Schwingungsdämpfer ist ein Feder‐Masse‐Dämpfer‐System, dessen dynamische Eigenschaften so auf das Bauwerk abgestimmt sind, dass die Trägheitskräfte den Bauwerksschwingungen durch einen Phasenversatz der Relativbewegung zwischen Bauwerk und Schwingungsdämpfer optimal entgegenwirken und diese reduzieren. Die Bemessung von Schwingungsdämpfern erfolgt entweder auf Grundlage numerischer Berechnungen oder durch Schwingungsversuche zur Ermittlung der dynamischen Eigenschaften des Bauwerks. Während der Lebensdauer eines Bauwerks können sich jedoch die dynamischen Eigenschaften, beispielsweise aufgrund von Alterungsprozessen, ändern, sodass die Wirksamkeit der Schwingungsdämpfer herabgesetzt wird. Im vorliegenden Beitrag wird eine Methode zur Beurteilung der Wirksamkeit von Schwingungsdämpfern unter Verwendung von Daten aus einem Structural‐Health‐Monitoring‐(SHM‐)System vorgestellt. Die Funktionalität des Schwingungsdämpfers wird durch Betrachtung des Phasenversatzes zwischen den Schwingungen des Bauwerks und des Dämpfers untersucht, wobei ein optimaler Dämpfungseffekt bei einer Phasenverschiebung von annähernd 90° zwischen diesen beiden Schwingungsantworten erwartet wird. Die vorgeschlagene Methode wird am Beispiel eines mit Schwingungsdämpfer und SHM‐System versehenen Sendeturms validiert.
Using chemiluminescence to determine whole blood antioxidant capacity in rheumatoid arthritis and Parkinson's disease patients
Authors: Hughes Diane L. , Richards Ross S. , Lexis Louise A.
Published: April 2018

The consequences of oxidative stress and inflammation are implicated in a wide range of diseases, including rheumatoid arthritis and Parkinson's disease. The status of antioxidant capacity in rheumatoid arthritis and Parkinson's disease remains unclear, in part due to common practice of assaying erythrocytes separately to plasma. This method removes any synergistic interactions between plasma and erythrocyte‐based antioxidants. The experiments in this report tested antioxidant capacity in whole blood, erythrocytes and plasma by group and disease stage. Medically diagnosed patients were recruited along with appropriate control group participants. Fasting venous blood was assayed using chemiluminescence methods for: time to maximum light emitted, maximum light emitted, and plasma antioxidant capacity in vitamin E analogue units. Here we demonstrate that whole blood exhibits higher antioxidant capacity than either plasma or erythrocytes assayed separately. We report increased oxidative stress in the blood of rheumatoid arthritis patients by group (p = 0.018, p = 0.049). We show increased antioxidant capacity in Parkinson's disease patients by group (p < 0.001). For later stage Parkinson's disease patients, we report reduced oxidative stress (p = 0.025), and increased antioxidant capacity and for erythrocytes (p < 0.001, p = 0.004) and whole blood (p < 0.001, p = 0.003). Early stage Parkinson's disease showed higher antioxidant capacity on only one measure (p = 0.008). Whole blood chemiluminescence is a useful technique for determining redox status in disease and might help clarify the role of oxidative stress in rheumatoid arthritis and Parkinson's disease.
Potential of Pyridine Amphiphiles as Staphylococcal Nuclease Inhibitor
Authors: Sahareen Tabassum , Dey Poulomi , Mukherjee Sandipan , Das Gopal , Ramesh Aiyagari
Published: April 2018

The present study explores the potential of pyridine‐based synthetic amphiphiles C1 and C2 having 4‐carbon and 12‐carbon hydrophobic tails, respectively, as staphylococcal nuclease inhibitors. UV–visible titration with calf‐thymus DNA (CT‐DNA) revealed a hypochromic shift in the absorbance bands of C1 and C2, whereas fluorescence titration indicated a reduction in the emission intensity of the monomer bands of the amphiphiles. Interaction of deoxyribonuclease I (DNase 1) and micrococcal nuclease (MNase) with C1 or C2 led to a decrease in the emission intensity of tryptophan at λ=345 nm along with an increase in the monomer emission intensity of C1 and C2 at λ=375 nm for DNase I and excimer emission intensity at λ=470 nm for both DNase I and MNase. Scatchard's analysis indicated superior interaction of C2 with DNase I. Circular dichroism spectroscopy revealed major changes in the secondary structures of both DNase I and MNase upon interaction with the amphiphiles. A solution‐based nuclease assay in conjunction with gel electrophoresis indicated amphiphile‐mediated protection against nuclease‐directed DNA cleavage. Interestingly, C2 could render inhibition of nuclease present in the culture supernatant of Staphylococcus aureus MTCC 96, which highlights the therapeutic prospect of the amphiphile against S. aureus.
A Genetically Encoded Ratiometric pH Probe: Wavelength Regulation‐Inspired Design of pH Indicators
Authors: Berbasova Tetyana , Tahmasebi Nick Setare , Nosrati Meisam , Nossoni Zahra , Santos Elizabeth M. , Vasileiou Chrysoula , Geiger James H. , Borhan Babak
Published: April 2018

Mutants of human cellular retinol‐binding protein II (hCRBPII) were engineered to bind a julolidine retinal analogue for the purpose of developing a ratiometric pH sensor. The design relied on the electrostatic influence of a titratable amino acid side chain, which affects the absorption and, thus, the emission of the protein/fluorophore complex. The ratio of emissions obtained at two excitation wavelengths that correspond to the absorption of the two forms of the protein/fluorophore complex, leads to a concentration‐independent measure of pH.
Collision Characteristics for Predicting Particle Attrition and Pipe Wear in Conveying Systems
Authors: Uzi Avi , Levy Avi
Published: April 2018

Pipe wear and particle attrition are common and undesired effects when conveying particles in pipelines. An approach for predicting these effects to spare considerable efforts spent in trial and error to achieve the optimum operating conditions is reported. The model is composed of a one‐dimensional flow model that calculates the two‐phase flow dynamics, a one‐dimensional breakage algorithm (ODBA) to compute attrition of the particles, and a one‐dimensional erosion model (ODEM) to compute the erosion rate. The ODBA and ODEM exploit machine functions derived from simulations that define collision characteristics. Several collision characteristics were successfully generated universally; therefore, allowing the attrition and erosion models to stand alone in the examined ranges.
Multistage Processing of Tunable Aqueous Polymer Phase Impregnated Resins (TAPPIR®)
Authors: Kaplanow Irene , Stecker Joel , Schembecker Gerhard , Merz Juliane
Published: April 2018

A promising concept of aqueous two‐phase extraction (ATPE) is the Tunable Aqueous Polymer Phase Impregnated Resins (TAPPIR®) technology. Thereby, one phase of an aqueous two‐phase system (ATPS) is immobilized inside porous solids, which are then dispersed in the second aqueous phase. Beside extraction performance, the reusability of the impregnated solids for several cycles decides upon the competitiveness of TAPPIR®. Multistage extraction experiments using a polyethylene glycol 4000/citrate ATPS to partition lysozyme were investigated for TAPPIR® and ATPE. A stable impregnation was demonstrated for multiple cycles. Moreover, it was found that multistage extraction processes should not be designed on basis of the first extraction as the yield changes in the following stages.
Hydration of Concrete: The First Steps
Authors: Thissen Peter , Natzeck Carsten , Giraudo Nicolas , Weidler Peter , Wöll Christof
Published: April 2018

Concrete is the most important construction material used by mankind and, at the same time, one of the most complex substances known in materials science. Since this mineral compound is highly porous, a better understanding of its surface chemistry, and in particular the reaction with water, is urgently required to understand and avoid corrosion of infrastructure like buildings and bridges. We have gained insight into proton transfer from concrete upon contact with water by applying the so‐called Surface Science approach to a well‐defined mineral, Wollastonite. Data from IR (infrared) spectroscopy reveal that exposure of this calcium‐silicate (CS) substrate to H2O leads to dissociation and the formation of OH‐species. This proton transfer is a chemical reaction of key importance, since on the one hand it triggers the conversion of cement into concrete (a calcium‐silicate‐hydrate phase), but on the other hand also governs the corrosion of concrete. Interestingly, we find that no proton transfer takes place when the same surface is exposed to methanol. In order to understand this unexpected difference, the analysis of the spectroscopic data obtained was aided by a detailed, first‐principles computational study employing density functional theory (DFT). The combined experimental and theoretical effort allows derivation of a consistent picture of proton transfer reactions occurring in CS and CSH phases. Implications for strategies to protect this backbone of urban infrastructure from corrosion in harsh, aqueous environments will be discussed.
In Situ Fabrication of Hierarchical MTW Zeolite via Nanoparticle Assembly by a Tailored Simple Organic Molecule
Authors: Zhang Kai , Luo Shaojuan , Liu Zewei , Li Chao , Ke Zheng , Yan Xin , Wu Ying , Xi Hongxia
Published: April 2018

Amphiphilic surfactants are widely used as templates to synthesize hierarchically structured zeolites due to their multiple functions; however, piloting such new dual‐functional templates is limited by their time‐consuming nature and high cost. Herein, a simple organic molecule, without a long hydrophobic alkyl chain, was tailored from a gemini‐type, poly‐quaternary ammonium surfactant, and effectively used as a dual‐porogenic template to synthesize hierarchical MTW zeolite. Upon a range of synthesis parameter optimizations, our detailed characterization suggested that the hierarchical MTW zeolite would completely crystallize within 36 hours from the surface to the inside of quasi—spherical particles through in situ consumption of amorphous silicon and aluminum species; much faster than most of the hierarchical MTW zeolites generated by conventional methods. Moreover, the as‐prepared hierarchical MTW zeolite exhibited 4 times higher catalytic performance and lifetime of benzene‐propene alkylation compared to conventional MTW zeolite, while the introduced crystalline mesopores are of benefit to diffuse reactants, products, and coke depositions. Our strategy broadens the design of new templates in more effective ways to facilely synthesize versatile hierarchical zeolites for diverse applications, especially for those in which macromolecules are involved.
Of Thiols and Disulfides: Methods for Chemoselective Formation of Asymmetric Disulfides in Synthetic Peptides and Polymers
Authors: Schäfer Olga , Barz Matthias
Published: April 2018

In protein or peptide chemistry, thiols are frequently chosen as a chemical entity for chemoselective modification reactions. Although it is a well‐established methodology to address cysteines and homocysteines in aqueous media to form S−C bonds, possibilities for the chemoselective formation of asymmetric disulfides have been less approached. Focusing on bioreversibility in conjugation chemistry, the formation of disulfide bonds is highly desirable for the attachment of thiol‐containing bioactive agents to proteins or in cross‐linking reactions, because disulfide bonds can combine stability in blood with degradability inside cells. In this Concept article, recent approaches in the field of activating groups for thiol moieties incorporated in peptide and polymer materials are highlighted. Advantageous combinations of stability during synthesis of the material with high reactivity towards thiols are explored focusing on simplification and prevention of side reactions as well as additional deprotection and activation steps prior to disulfide formation. Moreover, applications of this chemistry are highlighted and future perspectives are envisioned.
A General One‐Pot Synthesis of 2H‐Indazoles Using an Organophosphorus–Silane System
Authors: Schoene Jens , Bel Abed Hassen , Schmieder Peter , Christmann Mathias , Nazaré Marc
Published: April 2018

A simple and direct approach for the regioselective construction of the privileged 2H‐indazole scaffold is described. The developed one‐pot strategy involves phospholene‐mediated N−N bond formation to access 2H‐indazoles. The amount of organophosphorus reagent was minimized by recycling the phospholene oxide with organosilane reductants. Starting from functionalized 2‐nitrobenzaldehydes and primary amines, a mild reductive cyclization, involving the use of commercially available phospholene oxide and silanes, delivered a wide variety of substituted 2H‐indazoles in good to excellent yields.
Multidentate Phosphanyl Phosphinines: Synthesis and Properties
Authors: Chen Xiaodan , Li Zhongshu , Grützmacher Hansjörg
Published: April 2018

With respect to the well‐developed chemistry of pyridines, that of phosphinines is in its infancy. There are still challenges to be overcome with respect to the development of simple syntheses and the application of phosphinine derivatives. Here, we show that sodium phosphinin‐2‐olate is a valuable building block to prepare multidentate phosphinine ligands, which in turn can be employed for the preparation of metal complexes. These PdII and RhI complexes were fully characterized, including by NMR spectra and single‐crystal X‐ray diffraction studies, which clearly demonstrate that molecules R3−xP(O‐phosphinine)x with one, two, and three phosphinines (x=1, 2, 3) can be tethered to a central phosphorus donor center to give bis‐, tris‐, and tetradentate ligands.
Carboxylates as Nucleophiles in the Enantioselective Ring‐Opening of Formylcyclopropanes under Iminium Ion Catalysis
Authors: Díaz Estibaliz , Reyes Efraim , Uria Uxue , Carrillo Luisa , Tejero Tomas , Merino Pedro , Vicario Jose L.
Published: April 2018

In this work, carboxylic acids, which are typically regarded as poor nucleophiles, are demonstrated to be competent reagents to promote the ring‐opening of formylcyclopropanes after activation of the latter through iminium ion formation. Under optimized reaction conditions, a variety of γ‐acyloxy‐substituted aldehydes can be obtained in high yields and enantioselectivities through the desymmetrization of substituted meso‐formylcyclopropanes in the presence of a chiral secondary amine as catalyst.
Hydrazo‐CEST: Hydrazone‐Dependent Chemical Exchange Saturation Transfer Magnetic Resonance Imaging Contrast Agents
Authors: Dang Trina , Suchy Mojmír , Truong Yen J. , Oakden Wendy , Lam Wilfred W. , Lazurko Caitlin , Facey Glenn , Stanisz Greg J. , Shuhendler Adam J.
Published: April 2018

The rapid formation of hydrazones under physiological conditions was exploited for the detection of aldehydes through chemical exchange saturation transfer magnetic resonance imaging (CEST‐MRI). A metal‐free, diamagnetic contrast agent derived from N‐amino anthranilic acid was introduced, which selectively “turned‐on” upon hydrazone formation through an effect termed Hydrazo‐CEST. While the hydrazine form of the probe produced no CEST‐MRI signal enhancement, the formation of the aryl hydrazone resulted in >20 % intensity decrease in the bulk water signal through the CEST effect, as measured by 300 MHz 1H NMR, 3 T and 7 T MRI. Both the electronic contributions of the N‐amino anthranilate and the aldehyde binding partner were shown to directly impact the exchange rate of the proton on the ring‐proximal nitrogen, and thus the imaging signal. Additionally, the presence of the carboxylic acid moiety ortho to the hydrazine was necessary not only for contrast production, but also for rapid hydrazone formation and prolonged hydrazone product stability under physiological conditions. This work provided the first example of an MRI‐based contrast agent capable of a “turn on” response upon reaction with bioactive aldehydes, and outlined both the structural and electronic requirements to expand on Hydrazo‐CEST, a novel, hydrazone‐dependent subtype of diamagnetic CEST‐MRI.
Improving therapy for patients with epidermal growth factor receptor‐mutant lung cancer
Authors: Arbour Kathryn C. , Riely Gregory J.
Published: April 2018

Progress in the rational development of therapy for patients with epidermal growth factor receptor‐mutant lung cancer depends on pursuing multiple parallel approaches to the problem of resistance. New treatment strategies evaluating not only new drugs, but also novel dosing strategies and novel combinations based on off‐target mechanisms of resistance and general principles of tumor biology, have great potential to improve treatments for patients with epidermal growth factor receptor‐mutant lung cancer.

See also pages 2355‐64, this issue.
Erlotinib plus either pazopanib or placebo in patients with previously treated advanced non–small cell lung cancer: A randomized, placebo‐controlled phase 2 trial with correlated serum proteomic signatures
Authors: Spigel David R. , Burris Howard A. , Greco F. Anthony , Shih Kent C. , Gian Victor G. , Lipman Andrew J. , Daniel Davey B. , Waterhouse David M. , Finney Lindsey , Heymach John V. , Hainsworth John D.
Published: April 2018

BACKGROUND

This study compared the efficacy and safety of treatment with erlotinib plus pazopanib versus erlotinib plus placebo in patients with previously treated advanced non–small cell lung cancer (NSCLC).

METHODS

Patients with progressive‐stage IV NSCLC after either 1 or 2 previous chemotherapy regimens were randomized to receive erlotinib (150 mg by mouth daily) with either pazopanib (600 mg by mouth daily) or placebo. During treatment, patients were evaluated every 8 weeks until disease progression or unacceptable toxicity. After a study amendment, pretreatment serum specimens for the VeriStrat assay were collected. The predictive value of the VeriStrat score (good vs poor) for progression‐free survival (PFS) and overall survival (OS) was assessed in the overall population and in each treatment group.

RESULTS

One hundred ninety‐two eligible patients were randomized between February 2010 and February 2011. PFS was prolonged with erlotinib plus pazopanib versus erlotinib plus placebo (median, 2.6 vs 1.8 months; hazard ratio, 0.58; P = .001). There was no difference in the OS of the 2 groups. A good VeriStrat score predicted longer PFS and OS in the entire group and predicted longer PFS in the subgroup receiving erlotinib plus pazopanib. The addition of pazopanib increased toxicity, and this was consistent with the known toxicity profile.

CONCLUSIONS

The addition of pazopanib to erlotinib in an unselected group of patients with previously treated NSCLC improved PFS and increased treatment‐related toxicity, but it had no influence on OS. The efficacy of both regimens was modest. Patients receiving erlotinib plus pazopanib had longer PFS if they had a good VeriStrat score versus a poor one. Cancer 2018;124:2355‐64. © 2018 American Cancer Society.
Autologous transplantation versus allogeneic transplantation in patients with follicular lymphoma experiencing early treatment failure
Authors: Smith Sonali M. , Godfrey James , Ahn Kwang Woo , DiGilio Alyssa , Ahmed Sairah , Agrawal Vaibhav , Bachanova Veronika , Bacher Ulrike , Bashey Asad , Bolaños‐Meade Javier , Cairo Mitchell , Chen Andy , Chhabra Saurabh , Copelan Edward , Dahi Parastoo B. , Aljurf Mahmoud , Farooq Umar , Ganguly Siddhartha , Hertzberg Mark , Holmberg Leona , Inwards David , Kanate Abraham S. , Karmali Reem , Kenkre Vaishalee P. , Kharfan‐Dabaja Mohamed A. , Klein Andreas , Lazarus Hillard M. , Mei Matthew , Mussetti Alberto , Nishihori Taiga , Ramakrishnan Geethakumari Praveen , Saad Ayman , Savani Bipin N. , Schouten Harry C. , Shah Nirav , Urbano‐Ispizua Alvaro , Vij Ravi , Vose Julie , Sureda Anna , Hamadani Mehdi
Published: April 2018

BACKGROUND

Early treatment failure (ETF) in follicular lymphoma (FL), defined as relapse or progression within 2 years of frontline chemoimmunotherapy, is a newly recognized marker of poor survival and identifies a high‐risk group of patients with an expected 5‐year overall survival (OS) rate of approximately 50%. Transplantation is an established option for relapsed FL, but its efficacy in this specific ETF FL population has not been previously evaluated.

METHODS

This study compared autologous hematopoietic stem cell transplantation (auto‐HCT) with either matched sibling donor (MSD) or matched unrelated donor (MUD) allogeneic hematopoietic cell transplantation (allo‐HCT) as the first transplantation approach for patients with ETF FL (age ≥ 18 years) undergoing auto‐HCT or allo‐HCT between 2002 and 2014. The primary endpoint was OS. The secondary endpoints were progression‐free survival, relapse, and nonrelapse mortality (NRM).

RESULTS

Four hundred forty FL patients had ETF (auto‐HCT, 240; MSD hematopoietic stem cell transplantation [HCT], 105; and MUD HCT, 95). With a median follow‐up of 69 to 73 months, the adjusted probability of 5‐year OS was significantly higher after auto‐HCT (70%) or MSD HCT (73%) versus MUD HCT (49%; P = .0008). The 5‐year adjusted probability of NRM was significantly lower for auto‐HCT (5%) versus MSD (17%) or MUD HCT (33%; P < .0001). The 5‐year adjusted probability of disease relapse was lower with MSD (31%) or MUD HCT (23%) versus auto‐HCT (58%; P < .0001).

CONCLUSIONS

Patients with high‐risk FL, as defined by ETF, undergoing auto‐HCT for FL have low NRM and a promising 5‐year OS rate (70%). MSD HCT has lower relapse rates than auto‐HCT but similar OS. Cancer 2018;124:2541‐51. © 2018 American Cancer Society.
A symptom‐based model to predict colorectal cancer in low‐resource countries: Results from a prospective study of patients at high risk for colorectal cancer
Authors: Alatise Olusegun Isaac , Ayandipo Omobolaji O. , Adeyeye Ademola , Seier Ken , Komolafe Akinwunmi O. , Bojuwoye Matthew O. , Afuwape Oludapo O. , Zauber Ann , Omisore Adeleye , Olatoke Samuel , Akere Adegboyega , Famurewa Olusola , Gonen Mithat , Irabor David O. , Kingham T. Peter
Published: April 2018

BACKGROUND

Colorectal cancer (CRC) rates in low‐resource countries, which typically lack CRC screening programs, are rising. This study determined whether a risk model for patients with rectal bleeding could identify patients with curable CRC.

METHODS

This prospective, cross‐sectional study evaluated a model constructed from data from 1 hospital and validated at 2 other hospitals. The primary endpoint was the ability of the model to predict CRC, as diagnosed by colonoscopy, from clinical characteristics. The secondary endpoint was to determine the percentage of patients who had CRC.

RESULTS

Consecutive patients who were 45 years old or older and had self‐reported rectal bleeding for more than 1 week were evaluated. From January 2014 to July 2016, 362 patients answered a questionnaire and underwent colonoscopy. In the validation cohort, 56% of patients with rectal bleeding, weight loss, and changes in bowel habits had CRC, whereas 2% of patients with bleeding alone did. Overall, 18.2% of the patients had CRC, and 8.6% had adenomas. The proportion of CRC patients with potentially curable stage II or III disease was 74%, whereas the historical rate was 36%. The combination of rectal bleeding with both symptoms significantly predicted CRC in the validation set (odds ratio, 12.8; 95% confidence interval, 4.6‐35.4; P < .001).

CONCLUSIONS

In low‐resource settings, patients with rectal bleeding, weight loss, and changes in bowel habits should be classified as high risk for CRC. Patients with a high risk score should be prioritized for colonoscopy to increase the number of patients diagnosed with potentially curable CRC. Cancer 2018;124:2766‐2773. © 2018 American Cancer Society
Molecular Engineering of Zinc‐Porphyrin Sensitisers for p‐Type Dye‐Sensitised Solar Cells
Authors: Lu Jianfeng , Liu Zonghao , Pai Narendra , Jiang Liangcong , Bach Udo , Simonov Alexandr N. , Cheng Yi‐Bing , Spiccia Leone
Published: April 2018

Design of novel efficient light‐harvesters for p‐type dye‐sensitised solar cells (DSSCs) is indispensable for further advances in this photovoltaic technology. Herein, a novel D‐π‐A (D=donor, π=π‐conjugated linker, A=acceptor) sensitiser, ZnP1, featuring an electron acceptor, perylenemonoimide (PMI), connected to an electron donor, di(p‐carboxyphenyl)amine (DCPA), through fluorene and a zinc(II) porphyrin with alkyl chains as a π‐conjugated bridge is introduced. Spectroscopic and electrochemical characterisation of this dye along with a newly synthesised PMI‐free reference dye ZnP0 has been undertaken to demonstrate strong electron coupling between the DCPA donor and PMI acceptor subunits through the porphyrin ring in ZnP1, which redshifts the light absorption onset to the near‐IR region. When integrated into p‐DSSCs based on a mesoporous nickel(II) oxide semiconductor electrode and a tris(acetylacetonato) iron(III/II) redox mediator, ZnP1 exhibits an onset of the incident photon‐to‐current conversion efficiency at 800 nm and a power conversion efficiency of up to 0.92 % under simulated 100 mW cm−2 AM 1.5 G irradiation. This is the highest efficiency of the porphyrin‐based p‐DSSCs hitherto reported.
Enhanced Green Upconversion Emission From α‐NaYF4:Yb, Er Nanoparticles Embedded Silica Inverse Opal Heterostructure
Authors: Shrivastava Vishnu Prasad , Kumar Jitendra , Sivakumar Sri
Published: April 2018

Alfa (α)‐NaYF4: Yb, Er nanoparticles embedded silica inverse opal heterostructure, with dual photonic stop bands and negligible local thermal effects, was fabricated. This material exhibited improvement in its upconversion efficiency and green emission purity. The heterostructure was designed and constructed with a stack of two inverse opals with different periodicity to possess dual photonic stop bands at wavelengths λ≈410 and ≈660 nm with a passband in‐between (≈545 nm). Although the two photonic stop bands suppress two distant emission bands (blue: 2H9/2→4I15/2 and red: 4F9/2→4I15/2 transitions) simultaneously, the passband enhances the green emission bands corresponding to 2H11/2→4I15/2 and 4S3/2→4I15/2 transitions of Er3+ ions. The process leads to realization of a pure green color. In addition, the local thermal effects induced by laser irradiation at the surface of the nanoparticles are largely suppressed by effective dissipation of heat as a result of the microporous nature of the inverse opal heterostructures. The reduced thermal effect in embedded nanoparticles is advantageous and shown to be responsible for the enhancement of green emission, the increase or decrease in the luminescence lifetime of Er3+ ion 2H11/2 and 2H9/2 or 4S3/2 and 4F9/2 states, a faster luminescence rise time, and almost the same green‐to‐red intensity ratio with variation in laser power.
A model for first‐estimates of species‐specific, age‐specific mortality from centralized band‐recovery databases
Authors: Baylis Shane M. , Sunnucks Paul , Clarke Rohan
Published: April 2018

Population mortality curves, otherwise known as lifetime distribution functions, can be indispensable in many areas of ecology and environmental management including population viability and stock management analyses, disaster‐recovery monitoring, and fundamental evolutionary biology. Yet available modeling tools are often unable to estimate population mortality curves from commonly available datasets because these datasets fail to meet stringent experimental‐design requirements. Here, we present a new method for estimating population mortality curves from records of marked individuals found dead. Such data are increasingly accessible in some of the largest biological datasets, such as continent‐ or nation‐wide marking‐and‐recovery schemes for birds and other animals. The method accounts for known biases in availability by age class, variable monitoring effort through time, and mark loss. We show that our modeling approach generates accurate estimates of population mortality structure across a range of populations differing in marking histories, true mortality curves, monitoring regimes, and mark loss rates. Our approach can be applied to multiple species or groups at a time and can provide estimates of inter‐annual adult, immature, and first‐year survival rates, required by predictive modeling applications such as population viability analyses. Our approach is also capable of estimating apparent senescence rates for each population and facilitates evolutionary analyses of life‐history traits. For example, our method is potentially useful for exploring the evolution of senescence or for inter‐group comparisons of mortality rates where groups that differ by environment may be identified within mark‐recovery records. To demonstrate the efficacy of this method, we present fitted population mortality curves for a suite of seabird species represented in a national mark–recapture database.
Effects of spatial aggregation of nests on population recruitment: the case of a small population of Atlantic salmon
Authors: Bouchard Colin , Bardonnet Agnès , Buoro Mathieu , Tentelier Cédric
Published: April 2018

Spatial aggregation within a population is a widespread phenomenon which may both exacerbate local competition and the stochastic effect of local environmental perturbations. In particular, the spatial aggregation of nests may strongly affect recruitment and hence population dynamics. Although the negative effect of local density on local recruitment has often been theoretically extended to population dynamics, very few studies have demonstrated the effect of local aggregation on the whole population recruitment. Using a long‐term survey of a small Atlantic salmon population, we tested the effect of spatial aggregation on the whole population recruitment and whether accounting for population stock is important or not when explaining the population recruitment. We found that accounting for population stock is necessary and that spatial aggregation of nests improved estimates of population recruitment. The spatial aggregation of nests did not impact the average population recruitment; however, a stronger aggregation diminished the variability of population recruitment. Our findings suggest that the aggregation of nests among some breeding areas does not necessarily impair the whole population recruitment and significantly reduces the stochasticity of the recruitment. In addition, the aggregation of nests seems to be the result of an ideal distribution of females, selecting the best‐breeding sites. Our results also indicate that females select breeding sites on environmental risk to spawn within the safest sites. This study warns against the extrapolation of local density dependence observations to the population level, and advocates for investigating the effect of aggregation on the demographic and evolutionary population dynamics, a clear contribution of aggregation on population dynamic processes being found in the Nivelle population.
Synthesis, Characterization, and Photocatalytic Application of Type‐II CdS/Bi2W2O9 Heterojunction Nanomaterials towards Aerobic Oxidation of Amines to Imines
Authors: Bhoi Yagna Prakash , Mishra Braja G.
Published: April 2018

A series of new type‐II CdS/Bi2W2O9 heterojunction nanomaterials is prepared by a two stage process. Initially, phase‐pure Bi2W2O9, with orthorhombic crystalline structure, is prepared by a facile combustion‐synthesis route. The combustion‐synthesized Bi2W2O9 is subsequently modified by CdS nanoparticles using a hydrothermal route. The CdS/Bi2W2O9 heterojunctions are characterized using XRD, XPS, FTIR spectroscopy, UV/Vis DRS, PL, and FESEM and HRTEM studies. The occurrence of ultrafine CdS nanoparticles, with diameters of 8–15 nm, well‐dispersed over BWO plates, is inferred from microscopic characterization studies. The two crystalline phases exhibit microscopic close contact across grain boundaries, facilitating the transfer of excitons. The heterojunction materials exhibit improved visible‐light absorption, enhanced charge‐carrier separation, and suitable band‐alignment characteristics of a type‐II heterojunction. The CdS/Bi2W2O9 heterojunctions are evaluated as visible‐light‐active photocatalysts for the aerobic oxidation of amines to imines. Structurally and functionally diverse amine molecules are oxidized to the corresponding imines, with excellent selectivity, in a short span of time.
Evaluation of six sample preparation procedures for qualitative and quantitative proteomics analysis of milk fat globule membrane
Authors: Yang Yongxin , Anderson Elizabeth , Zhang Sheng
Published: April 2018

Proteomic analysis of membrane proteins is challenged by the proteins solubility and detergent incompatibility with MS analysis. No single perfect protocol can be used to comprehensively characterize the proteome of membrane fraction. Here, we used cow milk fat globule membrane (MFGM) proteome analysis to assess six sample preparation procedures including one in‐gel and five in‐solution digestion approaches prior to LC‐MS/MS analysis. The largest number of MFGM proteins were identified by suspension trapping (S‐Trap) and filter‐aided sample preparation (FASP) methods, followed by acetone precipitation without clean‐up of tryptic peptides method. Protein identifications with highest average coverage was achieved by Chloroform/MeOH, in‐gel and S‐Trap methods. Most distinct proteins were identified by FASP method, followed by S‐Trap. Analyses by Venn diagram, principal‐component analysis, hierarchical clustering and the abundance ranking of quantitative proteins highlight differences in the MFGM fraction by the all sample preparation procedures. These results reveal the biased proteins/peptides loss occurred in each protocol. In this study, we found several novel proteins that were not observed previously by in‐depth proteomics characterization of MFGM fraction in milk. Thus, a combination of multiple procedures with orthologous properties of sample preparation was demonstrated to improve the protein sequence coverage and expression level accuracy of membrane samples.
Anaerobic co‐digestion of waste yeast biomass from citric acid production and waste frying fat
Authors: Moeller Lucie , Bauer Aline , Zehnsdorf Andreas , Lee Mi‐Yong , Müller Roland Arno
Published: April 2018

The application of spent yeast for biogas production has been studied only in the context of breweries so far. This study is focused on the anaerobic digestion of concentrated yeast biomass (CYB), being a by‐product of citric acid biosynthesis. Two experimental set‐ups were used in order to test CYB as a mono‐substrate and co‐substrate for closing the loop in accordance with the ‘bioeconomy’ approach. The results show that CYB allows for obtaining a high biogas yield, with a maximum of 1.45 m3N/kgVS produced when CYB was used as a mono‐substrate. The average methane concentration was 66 ± 4%. However, anaerobic digestion of CYB alone was difficult to perform because of a tendency for over‐acidification, meaning that the maximum possible organic loading rate was 1 kg/(m3*d). Repeated clogging of tubes with coagulated biomass also disturbed continuous feeding. In contrast, the co‐digestion of CYB with waste frying fat at a ratio of 1:20 showed stable operation during a 70‐day fermentation period. The biogas yield using the substrate mixture was 1.42 m3/kgVS at an organic loading rate of 2 kg/(m3*d). The methane concentration reached 67 ± 4% and the acetate concentration did not exceed 30 mg/L during the entire fermentation.
Effect of Vemurafenib on the Pharmacokinetics of a Single Dose of Digoxin in Patients With BRAFV600 Mutation–Positive Metastatic Malignancy
Authors: Zhang Weijiang , McIntyre Christine , Kuhn Melissa , Forbes Harper , Kim Tae Min , Lee Jeeyun , Demidov Lev , Colburn Dawn
Published: April 2018

The primary objective of this phase 1, open‐label, multicenter, 3‐period, fixed‐sequence study was to evaluate the effect of multiple doses of vemurafenib on the pharmacokinetics of a single dose of digoxin, a probe P‐glycoprotein (P‐gp) substrate, in patients with BRAFV600 mutation‐positive metastatic malignancy. Following a 28‐day screening period, patients received a single oral dose of digoxin 0.25 mg on day 1 in period A, oral vemurafenib 960 mg twice daily for 21 days in period B (days 8‐28), and a single oral dose of digoxin 0.25 mg on day 29 and vemurafenib 960 mg twice a day for 7 days (days 29‐35) in period C. Log‐transformed area under the concentration‐time curve and peak concentration values for digoxin were compared between periods A (digoxin alone) and C (digoxin + vemurafenib) using an analysis of variance model. Twenty‐six patients were evaluated for the primary pharmacokinetic analysis. The geometric mean ratio (period C/period A) of area under the curve to the last measurable concentration for digoxin was 1.82 (90%CI 1.63 to 2.02), and the geometric mean ratio of peak concentrations was 1.47 (90%CI 1.30 to 1.65); the 90%CIs were outside of the equivalence limits of 0.82 to 1.22, indicating an effect of vemurafenib on digoxin. Multiple oral doses of vemurafenib were generally well tolerated, with an adverse event profile similar to that previously seen in phase 2 and 3 studies of vemurafenib monotherapy. This study confirmed vemurafenib as an inhibitor of P‐gp in vivo with a statistically significant drug‐drug interaction with digoxin. Caution should be exercised when dosing vemurafenib concurrently with P‐gp substrates.