bluuebunny/crossref_metadata_2025 huggingface dataset:
Precise point positioning performance in the presence of the 28 October 2003 sudden increase in total electron content
Authors: Rodríguez‐Bilbao I. , Radicella S. M. , Rodríguez‐Caderot G. , Herraiz M.
Published: September 2015

Intense disturbances in the ionosphere may produce perturbations in Global Navigation Satellite Systems (GNSS) radio signals that in the most severe cases produce receiver tracking problems, which in turn impact on GNSS positioning accuracy. In this paper we present a case study related to the sudden increase in total electron content (SITEC) induced by the X17.2 solar flare that occurred on 28 October 2003. This is the largest SITEC ever recorded by means of the rate of change of total electron content. A solar radio burst (SRB) occurred in the same period which caused GNSS signal fading and in some cases complete signal loss. Although SITEC contribution to the signal noise cannot be separated from that of SRB, in this paper we show that accuracy degradation may happen in kinematic precise point positioning (PPP) in several stations of the sunlit hemisphere when 30 s sampling rate data are analyzed. The observed errors in the position are the result of the difficulties that cycle slip (CS) detection strategies have to deal with the observables that have been affected by the SITEC.
Regioselective Oxidative Homocoupling Reaction: An Efficient Copper‐Catalyzed Synthesis of Biimidazo[1,2‐a]pyridines
Authors: Lei Sai , Cao Hua , Chen Longbin , Liu Jingyun , Cai Huiyin , Tan Jingwen
Published: September 2015

A facile and efficient copper(I)‐catalyzed intermolecular direct CH homocoupling of imidazo[1,2‐a]pyridines with excellent C‐3 regioselectivity in dimethyl sulfoxide (DMSO) has been developed. This transformation provides a straightforward and operationally simple route for the preparation of biimidazo[1,2‐a]pyridines which are an important structural motif in natural products and pharmaceuticals.

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Nickel‐Catalyzed Synthesis of Enamides and Enecarbamates via Isomerization of Allylamides and Allylcarbamates
Authors: Halli Juliette , Kramer Philipp , Bechthold Maren , Manolikakes Georg
Published: September 2015

A single‐component, air‐stable nickel precatalyst can catalyze the isomerization of allylamides for the synthesis of enamides. The scope of the reaction encompasses various substituted allylamides and allylcarbamates as well as homoallylamides. The reaction can be performed on a multigram‐scale without specialized glove‐box equipment or Schlenk techniques.

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Brook/Elimination/Aldol Reaction (BEAR) Sequence for the Direct Preparation of Fluorinated Aldols from β,β‐Difluoro‐α‐(trimethylsilyl)alcohols
Authors: Decostanzi Mélanie , Van Der Lee Arie , Campagne Jean‐Marc , Leclerc Eric
Published: September 2015

A methodology allowing the preparation of aldols featuring a fluorinated stereogenic center is reported. The corresponding fluoroenolates are formed in situ from stable β,β‐difluoro‐α‐(trimethylsilyl)alcohols, through a base‐mediated process involving a Brook rearrangement followed by a fluoride elimination, and are directly added to aromatic aldehydes. Two different sets of conditions were disclosed. The first one involves the stoichiometric addition of potassium tert‐butoxide (t‐BuOK) while the second is based on the use of a catalytic amount of an ammonium phenoxide. The latter opens the way for a catalytic and asymmetric version of this Brook/elimination/aldol reaction (BEAR) sequence.

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Integrated Process of Aerobic Oxidation–Olefination–Asymmetric CC Bond Formation Catalyzed by Robust Heterogeneous Gold/Palladium and Chirally Modified Rhodium Nanoparticles
Authors: Miyamura Hiroyuki , Suzuki Aya , Yasukawa Tomohiro , Kobayashi Shū
Published: September 2015

We have achieved an integrated process of oxidation–olefination–asymmetric 1,4‐addition reactions under aerobic and aqueous conditions using metal nanoparticles as robust heterogeneous catalysts. A tandem process of aerobic oxidation and Horner–Wadsworth–Emmons olefination was successfully catalyzed by gold/palladium bimetallic nanoparticles. A wide range of substrates gave the desired products in high yields and excellent selectivities. This tandem process was further connected with an asymmetric 1,4‐addition reaction catalyzed by chiral rhodium nanoparticles to achieve a challenging three‐step, one‐pot sequential reaction. Various types of esters with a chiral center at the β‐position were obtained from readily available and stable alcohols and arylboronic acids in high yields with high enantioselectivities in a one‐pot sequential reaction integrating three transformations.

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Layered Black Phosphorus as a Selective Vapor Sensor
Authors: Mayorga‐Martinez Carmen C. , Sofer Zdeněk , Pumera Martin
Published: September 2015

Black phosphorus is a layered material that is sensitive to the surrounding atmosphere. This is generally considered as a disadvantage, especially when compared to more stable layered compounds, such as graphite or MoS2. This sensitivity is now turned into an advantage. A vapor sensor that is based on layered black phosphorus and uses electrochemical impedance spectroscopy as the detection method is presented; the device selectively detects methanol vapor. The impedance phase measured at a constant frequency is used as a distinctive parameter for the selective quantification of methanol, and increases with the methanol concentration. The low detection limit of 28 ppm is well below the approved exposure limit of 200 ppm. The results are highly reproducible, and the vapor sensor is shown to be very selective in the presence of other vapors and to have long‐term stability.
Vielseitige, effiziente und ortsspezifische Proteinfunktionalisierung durch das Enzym Tubulin‐Tyrosin‐Ligase
Authors: Schumacher Dominik , Helma Jonas , Mann Florian A. , Pichler Garwin , Natale Francesco , Krause Eberhard , Cardoso M. Cristina , Hackenberger Christian P. R. , Leonhardt Heinrich
Published: September 2015

Mit dem so genannten “Tub‐tag labeling” haben wir eine neue chemoenzymatische Methode entwickelt, welche die einfache und schnelle ortsspezifische Modifikation von Proteinen erlaubt. Durch die Uminterpretation rekombinanter Tubulin‐Tyrosin‐Ligase können verschiedene nichtnatürliche und bioorthogonal reaktive Tyrosinderivate in Proteine eingebaut werden, welche mit einer kurzen, vom Tubulin abgeleiteten Peptidsequenz (Tub‐tag) ausgestattet sind. Wie anhand der ortsspezifischen Modifikation von Nanobodies, GFP und Ubiquitin gezeigt, ermöglicht diese neuartige Strategie eine Reihe effizienter, schneller und chemoselektiver Modifikationen am C‐Terminus von sowohl isolierten Proteinen als auch solchen in komplexen Zelllysaten. Somit ergeben sich vielseitige Anwendungen im Bereich der Biochemie, der Zellbiologie und darüber hinaus.
Acyl Radicals from Aromatic Carboxylic Acids by Means of Visible‐Light Photoredox Catalysis
Authors: Bergonzini Giulia , Cassani Carlo , Wallentin Carl‐Johan
Published: September 2015

Simple and abundant carboxylic acids have been used as acyl radical precursor by means of visible‐light photoredox catalysis. By the transient generation of a reactive anhydride intermediate, this redox‐neutral approach offers a mild and rapid entry to high‐value heterocyclic compounds without the need of UV irradiation, high temperature, high CO pressure, tin reagents, or peroxides.
From a Si3‐Cyclopropene to a Si3S‐Bicyclo[1.1.0]butane to a Si3S‐Cyclopropene to a Si3S2‐Bicyclo[1.1.0]butane: Back‐and‐Forth, and In‐Between
Authors: Lee Vladimir Ya. , Gapurenko Olga A. , Miyazaki Shogo , Sekiguchi Akira , Minyaev Ruslan M. , Minkin Vladimir I. , Gornitzka Heinz
Published: September 2015

Compact and highly reactive bicyclo[1.1.0]butanes constitute one of the most fascinating classes of organic compounds. Furthermore, interplay of bicyclo[1.1.0]butanes with their valence isomers, such as buta‐1,3‐dienes and cyclobutenes, is among the fundamental pericyclic transformations in organic chemistry. Herein we report the back‐and‐forth interconversion between the cyclotrisilenes and thiatrisilabicyclo[1.1.0]butanes, allowing for the synthesis of novel representatives of such classes of highly reactive organometallics. The peculiar structural and bonding features of the newly synthesized compounds, as well as the mechanism of their isomerization, were verified both experimentally and computationally.
Iron‐Catalyzed α‐Alkylation of Ketones with Alcohols
Authors: Elangovan Saravanakumar , Sortais Jean‐Baptiste , Beller Matthias , Darcel Christophe
Published: September 2015

A general and benign iron‐catalyzed α‐alkylation reaction of ketones with primary alcohols has been developed. The key to success of the reaction is the use of a Knölker‐type complex as catalyst (2 mol %) in the presence of Cs2CO3 as base (10 mol %) under hydrogen‐borrowing conditions. Using 2‐aminobenzyl alcohol as alkylation reagent allows for the “green” synthesis of quinoline derivatives.
Catalytic Nucleophilic Fluorination of Secondary and Tertiary Propargylic Electrophiles with a Copper–N‐Heterocyclic Carbene Complex
Authors: Cheng Li‐Jie , Cordier Christopher J.
Published: September 2015

A catalytic method for the nucleophilic fluorination of propargylic electrophiles is described. Our protocol involves the use of a Cu(NHC) complex as the catalyst and is suitable for the preparation of secondary and tertiary propargylic fluorides without the formation of isomeric fluoroallenes. Preliminary mechanistic investigations suggest that fluorination proceeds via copper acetylides and that cationic species are involved.
Enantiomerenreine Tribenzotriquinacene durch stereoselektive Synthese
Authors: Greschner Wilko , Neumann Beate , Stammler Hans‐Georg , Gröger Harald , Kuck Dietmar
Published: September 2015

Inhärent chirale Acetophenone und Benzaldehyde, die sich von dem großen, schalenförmig gebauten Gerüst des Tribenzotriquinacens (TBTQ) ableiten, wurden durch Enzymkatalyse enantiomerenrein synthetisiert. Unter Verwendung der Lipase CAL‐B gelangt man in fünf Stufen zu den (M)‐Enantiomeren, (+)‐2‐Acetyl‐TBTQ (M)‐5 und (+)‐2‐Formyl‐TBTQ (M)‐6, während der Einsatz von Lipase PS zu den entsprechenden (P)‐Enantiomeren, (−)‐2‐Acetyl‐TBTQ (P)‐5 und (−)‐2‐Formyl‐TBTQ (P)‐6 führt, jeweils mit mindestens 99 % ee. Die absolute Konfiguration dieser rigiden 3D‐Bausteine wurde durch Einkristall‐Röntgenstrukturanalyse der Ketone 5 und durch die Analogie ihrer chiroptischen Eigenschaften mit denen der Aldehyde 6 ermittelt.
Silver(I)‐Catalyzed Diastereoselective Synthesis of anti‐1,2‐Hydroxyboronates
Authors: Joannou Matthew V. , Moyer Brandon S. , Goldfogel Matthew J. , Meek Simon J.
Published: September 2015

A catalytic protocol for the diastereoselective synthesis of anti‐1,2‐hydroxyboronates is described. The process provides access to secondary alkyl organoborons. The deborylative 1,2‐addition reactions of alkyl 1,1‐diborons proceed in the presence of a silver(I) salt with either KOtBu or nBuLi as an activator. The catalytic diastereoselective protocol can be extended to aryl, alkenyl, and alkyl aldehydes with up to 99:1 d.r.
Halogen Bonding to Amplify Luminescence: A Case Study Using a Platinum Cyclometalated Complex
Authors: Sivchik Vasily V. , Solomatina Anastasia I. , Chen Yi‐Ting , Karttunen Antti J. , Tunik Sergey P. , Chou Pi‐Tai , Koshevoy Igor O.
Published: September 2015

The cocrystallization of a weakly luminescent platinum complex [Pt(btpy)(PPh3)Cl] (1) (Hbtpy=2‐(2benzothienyl)pyridine; emission quantum yield Φem=0.03) with fluorinated bromo‐ and iodoarenes C6F6‐nXn (X=Br, I; n=1, 2) results in the formation of efficient halogen‐bonding (XB) interactions PtCl⋅⋅⋅XR. An up to 22‐fold enhancement (Φem=0.65) in the luminescence intensity of the cocrystallized compound is detected, without a substantial change of the emission energy. Based on crystallographic, photophysical, and theoretical investigations, the contribution of the XB donors C6F6‐nXn to the amplification of luminescence intensity is attributed to the enhancement of spin–orbit coupling through the heavy‐atom effect, and simultaneously to the suppression of the nonradiative relaxation pathways by increasing the rigidity of the chromophore center.
2H and 139La NMR Spectroscopy in Aqueous Solutions at Geochemical Pressures
Authors: Ochoa Gerardo , Pilgrim Corey D. , Martin Michele N. , Colla Christopher A. , Klavins Peter , Augustine Matthew P. , Casey William H.
Published: September 2015

Nuclear spin relaxation rates of 2H and 139La in LaCl3+2H2O and La(ClO4)3+2H2O solutions were determined as a function of pressure in order to demonstrate a new NMR probe designed for solution spectroscopy at geochemical pressures. The 2H longitudinal relaxation rates (T1) vary linearly to 1.6 GPa, consistent with previous work at lower pressures. The 139La T1 values vary both with solution chemistry and pressure, but converge with pressure, suggesting that the combined effects of increased viscosity and enhanced rates of ligand exchange control relaxation. This simple NMR probe design allows experiments on aqueous solutions to pressures corresponding roughly to those at the base of the Earth’s continental crust.
Quaternary Stereogenic Centers through Enantioselective Heck Arylation of Acyclic Olefins with Aryldiazonium Salts: Application in a Concise Synthesis of (R)‐Verapamil
Authors: Oliveira Caio C. , Pfaltz Andreas , Correia Carlos Roque Duarte
Published: September 2015

We describe herein a highly regio‐ and enantioselective Pd‐catalyzed Heck arylation of unactivated trisubstituted acyclic olefins to provide all‐carbon quaternary stereogenic centers. Chiral N,N ligands of the pyrimidine‐ and pyrazino‐oxazoline class were developed for that purpose, providing the desired products in good to high yields with enantiomeric ratios up to >99:1. Both linear and branched substituents on the olefins were well‐tolerated. The potential of this new method is demonstrated by the straightforward synthesis of several O‐methyl lactols and lactones containing quaternary stereocenters, together with a concise enantioselective total synthesis of the calcium channel blocker verapamil.
Nitrogen‐Doped Carbon Nanotube Arrays for High‐Efficiency Electrochemical Reduction of CO2: On the Understanding of Defects, Defect Density, and Selectivity
Authors: Sharma Pranav P. , Wu Jingjie , Yadav Ram Manohar , Liu Mingjie , Wright Christopher J. , Tiwary Chandra Sekhar , Yakobson Boris I. , Lou Jun , Ajayan Pulickel M. , Zhou Xiao‐Dong
Published: September 2015

Nitrogen‐doped carbon nanotubes (NCNTs) have been considered as a promising electrocatalyst for carbon‐dioxide‐reduction reactions, but two fundamental chemistry questions remain obscure: 1) What are the active centers with respect to various defect species and 2) what is the role of defect density on the selectivity of NCNTs? The aim of this work is to address these questions. The catalytic activity of NCNTs depends on the structural nature of nitrogen in CNTs and defect density. Comparing with pristine CNTs, the presence of graphitic and pyridinic nitrogen significantly decreases the overpotential (ca. −0.18 V) and increases the selectivity (ca. 80 %) towards the formation of CO. The experimental results are in congruent with DFT calculations, which show that pyridinic defects retain a lone pair of electrons that are capable of binding CO2. However, for graphitic‐like nitrogen, electrons are located in the π* antibonding orbital, making them less accessible for CO2 binding.
Stimulation of In Vivo Antitumor Immunity with Hollow Mesoporous Silica Nanospheres
Authors: Wang Xiupeng , Li Xia , Ito Atsuo , Watanabe Yohei , Sogo Yu , Tsuji Noriko M. , Ohno Tadao
Published: September 2015

The use of appropriate adjuvants that support the generation of robust and long‐lasting antitumor immune responses is crucial for tumor immunotherapy owing to the immunosuppressive environment of the growing tumor. However, the most commonly used adjuvant, aluminum hydroxide, is ineffective for generating such immune responses and therefore not suitable for cancer immunotherapy. It is now shown that plain hollow mesoporous silica nanospheres markedly improve the antitumor immunity, the Th1 and Th2 immunity, and the CD4+ and CD8+ effector memory T cell population in bone marrow in vivo and may thus be used as immunoadjuvants to treat cancer in humans.
Three‐State Single‐Molecule Naphthalenediimide Switch: Integration of a Pendant Redox Unit for Conductance Tuning
Authors: Li Yonghai , Baghernejad Masoud , Qusiy Al‐Galiby , Zsolt Manrique David , Zhang Guanxin , Hamill Joseph , Fu Yongchun , Broekmann Peter , Hong Wenjing , Wandlowski Thomas , Zhang Deqing , Lambert Colin
Published: September 2015

We studied charge transport through core‐substituted naphthalenediimide (NDI) single‐molecule junctions using the electrochemical STM‐based break‐junction technique in combination with DFT calculations. Conductance switching among three well‐defined states was demonstrated by electrochemically controlling the redox state of the pendent diimide unit of the molecule in an ionic liquid. The electrical conductances of the dianion and neutral states differ by more than one order of magnitude. The potential‐dependence of the charge‐transport characteristics of the NDI molecules was confirmed by DFT calculations, which account for electrochemical double‐layer effects on the conductance of the NDI junctions. This study suggests that integration of a pendant redox unit with strong coupling to a molecular backbone enables the tuning of charge transport through single‐molecule devices by controlling their redox states.
Titanocene(III)‐Catalyzed Three‐Component Reaction of Secondary Amides, Aldehydes, and Electrophilic Alkenes
Authors: Zheng Xiao , He Jiang , Li Heng‐Hui , Wang Ao , Dai Xi‐Jie , Wang Ai‐E , Huang Pei‐Qiang
Published: September 2015

An umpolung Mannich‐type reaction of secondary amides, aliphatic aldehydes, and electrophilic alkenes has been disclosed. This reaction features the one‐pot formation of CN and CC bonds by a titanocene‐catalyzed radical coupling of the condensation products, from secondary amides and aldehydes, with electrophilic alkenes. N‐substituted γ‐amido‐acid derivatives and γ‐amido ketones can be efficiently prepared by the current method. Extension to the reaction between ketoamides and electrophilic alkenes allows rapid assembly of piperidine skeletons with α‐amino quaternary carbon centers. Its synthetic utility has been demonstrated by a facile construction of the tricyclic core of marine alkaloids such as cylindricine C and polycitorol A.
An Experimentally Established Key Intermediate in Benzene Nitration with Mixed Acid
Authors: Koleva Gergana , Galabov Boris , Hadjieva Boriana , Schaefer Henry F. , Schleyer Paul von R.
Published: September 2015

Experimental evidence is reported for the first intermediate in the classic SEAr reaction of benzene nitration with mixed acid. The UV/Vis spectroscopic investigation of the reaction showed an intense absorption at 320 nm (appearing as a band shoulder) arising from a reaction intermediate. Our theoretical modeling shows that the interaction between the two principal reactants with solvent (H2SO4) molecules significantly affects the structure of the initial complex. In this complex, a larger distance between the aromatic ring and nitronium ion precludes the possibility for electronic charge transfer from the benzene π‐system to the electrophile. The computational modeling of the potential energy surface reveals that the reaction favors a stepwise mechanism with intermediate formation of π‐ and σ‐ (arenium ion) complexes.
E–H Bond Activation of Ammonia and Water by a Geometrically Constrained Phosphorus(III) Compound
Authors: Robinson Thomas P. , De Rosa Daniel M. , Aldridge Simon , Goicoechea Jose M.
Published: September 2015

The synthesis of a phosphorus(III) compound bearing a N,N‐bis(3,5‐di‐tert‐butyl‐2‐phenoxy)amide ligand is reported. This species has been found to react with ammonia and water, activating the EH bonds in both substrates by formal oxidative addition to afford the corresponding phosphorus(V) compounds. In the case of water, both OH bonds can be activated, splitting the molecule into its constituent elements. To our knowledge, this is the first example of a compound based on main group elements that sequentially activates water in this manner.
Asymmetric Synthesis of Tetracyclic Pyrroloindolines and Constrained Tryptamines by a Switchable Cascade Reaction
Authors: de Graaff Corien , Bensch Lisa , Boersma Sjoerd J. , Cioc Răzvan C. , van Lint Matthijs J. , Janssen Elwin , Turner Nicholas J. , Orru Romano V. A. , Ruijter Eelco
Published: September 2015

The interrupted Fischer indole synthesis of arylhydrazines and biocatalytically generated chiral bicyclic imines selectively affords either tetracyclic pyrroloindolines or tricyclic tryptamine analogues depending on the reaction conditions. We demonstrate that the reaction is compatible with a variety of functional groups. The products are obtained in high optical purity and in reasonable to good yield. We present a plausible reaction mechanism to explain the observed reaction outcome depending on the stoichiometry of the acid mediator. To demonstrate the synthetic utility of our method, pharmaceutically relevant examples of both product classes were synthesized in highly efficient reaction sequences, including a phenserine analogue as a potential cholinesterase inhibitor and constrained tryptamine derivatives as selective inhibitors of the 5‐HT6 serotonin receptor and the TRPV1 ion channel.
Synthesis of Complexes with Abnormal “Protic” N‐Heterocyclic Carbenes
Authors: Jin Hanpeng , Tan Tristan Tsai Yuan , Hahn F. Ekkehardt
Published: September 2015

Neutral 4‐iodo‐N‐ethylimidazole 3 oxidatively adds to [Pt(PPh3)4] to give, in the presence of different tetraalkylammonium salts, complexes trans‐[4], trans‐[5], and trans‐[6] containing an anionic C4‐bound heterocycle with an unsubstituted ring‐nitrogen atom. Complex trans‐[4] reacts with the proton source NH4I under protonation of the ring‐nitrogen atom to produce complex trans‐[7]I which bears an NH,NR‐substituted aNHC ligand. The reaction of trans‐[4] with CH3I yields the complex trans‐[8]I which has a classical aNHC ligand with two alkylated ring‐nitrogen atoms.
Enantioselective Copper(I)‐Catalyzed Alkynylation of Oxocarbenium Ions to Set Diaryl Tetrasubstituted Stereocenters
Authors: Dasgupta Srimoyee , Rivas Thomas , Watson Mary P.
Published: September 2015

An enantioselective, copper(I)‐catalyzed addition of terminal alkynes to isochroman ketals to set diaryl, tetrasubstituted stereocenters has been developed. The success of this reaction relies on identification of a Cu/PyBox catalyst capable of distinguishing the faces of the diaryl‐substituted oxocarbenium ion. This challenging transformation enables efficient conversion of readily available, racemic ketals into high‐value enantioenriched isochroman products with fully substituted stereogenic centers. High yields and enantiomeric excesses are observed for various isochroman ketals and an array of alkynes.
Reduction of Carbon Dioxide to Formate at Low Overpotential Using a Superbase Ionic Liquid
Authors: Hollingsworth Nathan , Taylor S. F. Rebecca , Galante Miguel T. , Jacquemin Johan , Longo Claudia , Holt Katherine B. , de Leeuw Nora H. , Hardacre Christopher
Published: September 2015

A new low‐energy pathway is reported for the electrochemical reduction of CO2 to formate and syngas at low overpotentials, utilizing a reactive ionic liquid as the solvent. The superbasic tetraalkyl phosphonium ionic liquid [P66614][124Triz] is able to chemisorb CO2 through equimolar binding of CO2 with the 1,2,4‐triazole anion. This chemisorbed CO2 can be reduced at silver electrodes at overpotentials as low as 0.17 V, forming formate. In contrast, physically absorbed CO2 within the same ionic liquid or in ionic liquids where chemisorption is impossible (such as [P66614][NTf2]) undergoes reduction at significantly increased overpotentials, producing only CO as the product.
Symptom Assessment in Knee Osteoarthritis Needs to Account for Physical Activity Level
Authors: Lo Grace H. , McAlindon Timothy E. , Hawker Gillian A. , Driban Jeffrey B. , Price Lori Lyn , Song Jing , Eaton Charles B. , Hochberg Marc C. , Jackson Rebecca D. , Kwoh C. Kent , Nevitt Michael C. , Dunlop Dorothy D.
Published: September 2015

Objective

Pain is not always correlated with severity of radiographic osteoarthritis (OA), possibly because people modify activities to manage symptoms. Measures of symptoms that consider pain in the context of activity level may therefore provide greater discrimination than a measure of pain alone. We undertook this study to compare discrimination provided by a measure of pain alone with that provided by combined measures of pain in the context of physical activity across radiographic OA severity levels.

Methods

This was a cross‐sectional study nested within the Osteoarthritis Initiative (OAI). The population was drawn from 2,127 persons enrolled in an OAI accelerometer monitoring substudy, including those with and those without knee OA. Two composite pain and activity knee symptom (PAKS) scores were calculated as the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score (plus 1) divided by a physical activity measure (step count for the first PAKS score [PAKS1 score] and activity count for the second PAKS score [PAKS2 score]). Symptom score discrimination across Kellgren/Lawrence (K/L) grades was evaluated using histograms and quantile regression.

Results

A total of 1,806 participants (55.5% of whom were women) were included (mean ± SD age 65.1 ± 9.1 years, mean ± SD body mass index 28.4 ± 4.8 kg/m2). The WOMAC pain score, but not the PAKS scores, exhibited a floor effect. The adjusted median WOMAC pain scores by K/L grades 0–4 were 0, 0, 0, 1, and 3, respectively. The adjusted median PAKS1 scores were 24.9, 26.0, 32.4, 46.1, and 97.9, respectively, and the adjusted median PAKS2 scores were 7.2, 7.2, 9.2, 12.9, and 23.8, respectively. The PAKS scores had more statistically significant comparisons between K/L grades than did the WOMAC pain score.

Conclusion

Symptom assessments incorporating pain and physical activity did not exhibit a floor effect and were better able to discriminate radiographic severity than an assessment of pain alone, particularly in milder disease. Pain in the context of physical activity level should be used to assess knee OA symptoms.
Diagnosis and management of thrombosis in pregnancy
Authors: Konkle Barbara A.
Published: September 2015

Pregnancy‐related thrombosis is a major cause of maternal mortality. Pregnancy and the puerperium are associated with a fourfold to fivefold increased risk of thrombosis when compared with the nonpregnant state. The greatest time of risk is in the postpartum period. Diagnosis of venous thromboembolism (VTE) during pregnancy can be challenging as many of the symptoms can be associated with normal pregnancy. Almost all deep venous thrombosis occurs in the left leg or iliac veins. Diagnostic procedures for pulmonary embolism carry some exposure to radiation, although risks are low when compared with risks associated with an undiagnosed maternal PE. The anticoagulant of choice during pregnancy is low‐molecular‐weight heparin. Certain medical conditions require alternative approaches as management around the time of delivery. In women with VTE during pregnancy, anticoagulation should continue for at least 3 months and until at least 6 weeks postpartum. Birth Defects Research (Part C) 105:185–189, 2015. © 2015 Wiley Periodicals, Inc.
Nonclinical aspects of venous thrombosis in pregnancy
Authors: Struble Evi , Harrouk Wafa , DeFelice Albert , Tesfamariam Belay
Published: September 2015

Pregnancy is a hypercoagulable state which carries an excess risk of maternal venous thrombosis. Endothelial injury, alterations in blood flow and activation of the coagulation pathway are proposed to contribute to the hypercoagulability. The risk for thrombosis may be accentuated by certain drugs and device implants that directly or indirectly affect the coagulation pathway. To help ensure that these interventions do not result in adverse maternal or fetal outcomes during pregnancy, gravid experimental animals can be exposed to such treatments at various stages of gestation and over a dosage range that would identify hazards and inform risk assessment. Circulating soluble biomarkers can also be evaluated for enhancing the assessment of any increased risk of venous thrombosis during pregnancy. In addition to traditional in vivo animal testing, efforts are under way to incorporate reliable non‐animal methods in the assessment of embryofetal toxicity and thrombogenic effects. This review summarizes hemostatic balance during pregnancy in animal species, embryofetal development, biomarkers of venous thrombosis, and alterations caused by drug‐induced venous thrombosis. Birth Defects Research (Part C) 105:190–200, 2015. © 2015 Wiley Periodicals, Inc.
Characterization of intracranial atherosclerotic stenosis using high‐resolution MRI study – rationale and design
Authors: Turan Tanya N. , LeMatty Todd , Martin Renee , Chimowitz Marc I. , Rumboldt Zoran , Spampinato M. Vittoria , Stalcup Seth , Adams Robert J. , Brown Truman
Published: September 2015

Background

Intracranial atherosclerosis is a leading cause of stroke, but little is known about the composition of the intracranial atherosclerotic lesion and how intracranial plaque morphology is related to the risk of stroke. High‐resolution magnetic resonance imaging (HR MRI) has been used in patients with extracranial carotid atherosclerosis as an in vivo tool to identify, with high‐interrater agreement, histologically defined plaque components (i.e., intraplaque hemorrhage, fibrous cap, and lipid core), which have been shown to be predictors of recurrent stroke. With careful imaging the components of atherosclerotic plaque can be visualized in the intracranial arteries using HR MRI, but there are no reports of reproducibility or interrater reliability.

Methods/Study design

The Characterization of intracranial atherosclerotic stenosis using high‐resolution MRI (CHIASM) study is a single‐center NIH‐funded prospective observational study, to (1) demonstrate high ‐interrater agreement for identifying intracranial plaque components on HR MRI, (2) determine the frequency of these components in symptomatic versus asymptomatic plaques, and (3) estimate the 1‐year rate of stroke in the territory of high‐risk plaque components. CHIASM will recruit 90 patients with 50–99% intracranial atherosclerosis to undergo HRMRI of the intracranial artery plaque at enrollment and 1‐year follow‐up. Both symptomatic and asymptomatic subjects will be recruited.

Conclusion

Determination of good interrater reliability is an important first step in the development of HR MRI as a tool to predict risk in patients with intracranial atherosclerosis. This study will inform the design of future multicenter studies to determine the prevalence and prognosis of intracranial atherosclerotic plaque components. Such studies could lead to new understanding of the pathophysiological mechanisms of cerebral ischemia in patients with atherosclerotic intracranial stenosis, improvements in risk stratification, and potentially to new treatments of this common and serious disease.
Use of T1‐weighted/T2‐weighted magnetic resonance ratio images to elucidate changes in the schizophrenic brain
Authors: Iwatani Jun , Ishida Takuya , Donishi Tomohiro , Ukai Satoshi , Shinosaki Kazuhiro , Terada Masaki , Kaneoke Yoshiki
Published: September 2015

Introduction

One leading hypothesis suggests that schizophrenia (SZ) is a neurodevelopmental disorder caused by genetic defects in association with environmental risk factors that affect synapse and myelin formation. Recent magnetic resonance imaging (MRI) studies of SZ brain showed both gray matter (GM) reduction and white matter (WM) fractional anisotropy reduction. In this study, we used T1‐weighted (T1w)/T2‐weighted (T2w) MRI ratio images, which increase myelin‐related signal contrast and reduce receiver‐coil bias.

Methods

We measured T1w/T2w ratio image signal intensity in 29 patients with SZ and 33 healthy controls (HCs), and then compared them against bias‐corrected T1w images.

Results

Mean T1w/T2w ratio signal intensity values across all SZ GM and WM voxels were significantly lower than those for the HC values (analysis of covariance with age, gender, handedness, and premorbid intelligence quotient as nuisance covariates). SZ mean WM T1w/T2w ratio values were related to Global Assessment of Functioning (GAF) scores and were inversely related to the positive psychotic symptoms of the Positive and Negative Syndrome Scale. Voxel‐based analysis revealed significantly lower T1w/T2w ratio image signal intensity values in the right ventral putamen in SZ GM. T1w image intensities did not differ between the SZ and HC groups.

Conclusions

T1‐weighted/T2‐weighted ratio imaging increased the detectability of SZ pathological changes. Reduced SZ brain signal intensity is likely due to diminished myelin content; therefore, mapping myelin‐related SZ brain changes using T1w/T2w ratio images may be useful for studies of SZ brain abnormalities.
Observability analysis of biochemical process models as a valuable tool for the development of mechanistic soft sensors
Authors: Golabgir Aydin , Hoch Thomas , Zhariy Mariya , Herwig Christoph
Published: September 2015

By enabling the estimation of difficult‐to‐measure target variables using available indirect measurements, mechanistic soft sensors have become important tools for various bioprocess monitoring and control scenarios. Despite promising higher process efficiencies and increased process understanding, widespread application of soft sensors has been stalled by uncertainty about the feasibility and reliability of their estimations given present process analytical constraints. Observability analysis can provide an indication of the possibility and reliability of soft sensor estimations by analyzing the structural properties of first‐principle (mechanistic) models. In addition, it can provide a criteria for selection of suitable measurement methods with respect to their information content; thereby leading to successful implementation of soft sensors in bioprocess development and manufacturing environments. We demonstrate the utility of observability analysis for two classes of upstream bioprocesses: the processes involving growth and ethanol formation by Saccharomyces cerevisiae and the process of penicillin production by Penicillium chrysogenum. Results obtained from laboratory‐scale cultivations in addition to in‐silico experiments enable a comparison of theoretical aspects of observability analysis and the real‐life performance of soft sensors. By taking the expected error of measurements provided to the soft sensor into account, an innovative scaling approach facilitates a higher degree of comparability of observability results among various measurement configurations and process conditions. © 2015 American Institute of Chemical Engineers Biotechnol. Prog., 31:1703–1715, 2015
Surface anatomy and anatomical planes in the adult turkish population
Authors: Uzun C. , Atman E.D. , Ustuner E. , Mirjalili S.A. , Oztuna D. , Esmer T.S.
Published: September 2015

Surface anatomy and anatomical planes are widely used in education and clinical practice. The planes are largely derived from cadaveric studies and their projections on the skin show discrepancies between and within anatomical reference textbooks. In this study, we reassessed the accuracy of common thoracic and abdominopelvic anatomical planes using computed tomography (CT) imaging in the live adult Turkish population. After patients with distorting pathologies had been excluded, CT images of 150 supine patients at the end tidal inspiration were analyzed. Sternal angle, transpyloric, subcostal, supracristal and pubic crest planes and their relationships to anatomical structures were established by dual consensus. The tracheal bifurcation, azygos vein/superior vena cava (SVC) junction and pulmonary bifurcation were usually below the sternal angle while the concavity of the aortic arch was generally within the plane. The tip of the tenth rib, the superior mesenteric artery and the portal vein were usually within the transpyloric plane while the renal hila and the fundus of the gallbladder were below it. The inferior mesenteric artery was below the subcostal plane and the aortic bifurcation was below the supracristal plane in most adults. Projectional surface anatomy is fundamental to medical education and clinical practice. Modern cross‐sectional imaging techniques allow large groups of live patients to be examined. Classic textbook information regarding anatomy needs to be reviewed and updated using the data gathered from these recent studies, taking ethnic differences into consideration. Clin. Anat. 29:183–190, 2016. © 2015 Wiley Periodicals, Inc.
Understanding Ni Promotion of MoS2/γ‐Al2O3 and its Implications for the Hydrogenation of Phenanthrene
Authors: Schachtl Eva , Zhong Lei , Kondratieva Elena , Hein Jennifer , Gutiérrez Oliver Y. , Jentys Andreas , Lercher Johannes A.
Published: September 2015

The chemical composition and structure of NiMo sulfides supported on γ‐Al2O3 and its properties for hydrogenation of polyaromatic compounds is explored. The presence of Ni favors the formation of disperse octahedrally coordinated Mo in the oxide precursors and facilitates its reduction during sulfidation. This decreases the particle size of MoS2 (measured by transmission electron microscopy) and increases the concentration of active sites up to a Ni/(Mo+Ni) atomic ratio of 0.33. At higher Ni loadings, the size of the MoS2 did not decrease further, although the concentration of adsorption sites and accessible Ni atoms decreased. This is attributed to the formation of NiSx clusters at the edges of MoS2. Nickel also interacts with the support, forming separated NiSx clusters, and is partially incorporated into the γ‐Al2O3, forming a Ni‐spinel. The hydrogenation of phenanthrene follows two pathways; by adding one or two H2 molecules, 9,10‐dihydrophenanthrene or 1,2,3,4‐tetrahydrophenanthrene are formed as primary products. Only symmetric hydrogenation, leading to 9,10‐dihydrophenanthrene, was observed on unpromoted MoS2/γ‐Al2O3. In contrast, symmetric and deep hydrogenation (leading to 9,10‐dihydrophenanthrene and 1,2,3,4‐tetrahydrophenanthrene, respectively) occur with similar selectivity on Ni‐promoted MoS2/γ‐Al2O3. The rates of both pathways increase linearly with the concentration of Ni atoms in the catalyst. The higher rates for symmetric hydrogenation are attributed to increasing concentrations of reactive species at the surface, and deep hydrogenation is concluded to be catalyzed by Ni at the edge of MoS2 slabs.
Synthesis of Supported RhMo and PtMo Bimetallic Catalysts by Controlled Surface Reactions
Authors: Alba‐Rubio Ana C. , Sener Canan , Hakim Sikander H. , Gostanian Thomas M. , Dumesic James A.
Published: September 2015

We previously described a synthesis method to prepare bimetallic catalysts with narrow nanoparticle size and composition distributions by means of controlled surface reactions (CSR) between a reduced supported metal nanoparticle and an organometallic precursor of an oxophilic promoter metal. Herein, we report a comparison of such catalysts with those prepared by traditional incipient wetness impregnation. STEM/EDS analysis indicates that catalysts prepared by CSR exhibit more effective interaction of metals, thereby minimizing the undesirable formation of component‐rich nanoparticles and/or monometallic domains. Reaction kinetics studies using these bimetallic catalysts reveal that optimal conversion rates in a selective CO hydrogenolysis reaction (i.e., hydrogenolysis of 2‐(hydroxymethyl)tetrahydropyran to 1,6‐hexanediol) could be achieved using a lower amount of the oxophilic promoter metal for the catalysts prepared by the CSR approach, as compared to their impregnated counterparts.
Distribution of Metal Cations in Ni‐Mo‐W Sulfide Catalysts
Authors: Hein Jennifer , Gutiérrez Oliver Y. , Schachtl Eva , Xu Pinghong , Browning Nigel D. , Jentys Andreas , Lercher Johannes A.
Published: September 2015

The distribution of metal cations and the morphology of unsupported NiMo, NiW, and NiMoW sulfide catalysts were explored qualitatively and quantitatively. In the bi‐ and trimetallic catalysts, Mo(W)S2 nanoparticles are deposited on Ni sulfide particles of varying stoichiometry and sizes (crystalline Ni9S8, and Ni3S4 were identified). These nanoparticles are stacks of Mo(W)S2 slabs with varying size, degrees of bending and mismatch between the slabs. High resolution electron microscopy and X‐ray absorption spectroscopy based on particle modeling revealed a statistical distribution of Mo and W within individual layers in sulfide NiMoW, forming intralayer mixed Mo1−xWxS2. Ni is associated with MoS2, WS2, and Mo1−xWxS2 creating Ni‐promoted phases. The incorporation of Ni at the edges of the slabs was the highest for sulfide NiMoW. This high concentration of Ni in sulfide NiMoW, as well as its long bent Mo1−xWxS2 slabs, were paralleled by the highest activity for nitrogen and sulfur removal from model hydrocarbons such as o‐propylaniline and dibenzothiophene.
Preparation of Nickel Phosphide Hydrodesulfurization Catalysts Assisted by Supercritical Carbon Dioxide
Authors: Motos‐Pérez Blanca , Uzio Denis , Aymonier Cyril
Published: September 2015

The front cover artwork for Issue 21/2015 is a collaboration between the Catalysis & Separation Division, IFPEN and ICMCB–CNRS. The image shows a new preparation method to obtain silica‐supported nickel phosphide nanoparticles assisted by supercritical carbon dioxide and their application to hydrodesulfurization. See the Communication itself at http://dx.doi.org/10.1002/cctc.201500755.
Synthetic Routes to Coelenterazine and Other Imidazo[1,2‐a]pyrazin‐3‐one Luciferins: Essential Tools for Bioluminescence‐Based Investigations
Authors: Coutant Eloi P. , Janin Yves L.
Published: September 2015

In the last few decades, bioluminescent systems based on the expression of a luciferase and the addition of a luciferin to monitor the emission of light have become very important tools for biological investigations. A growing proportion of these systems use coelenterazine or analogues of imidazo[1,2‐a]pyrazine luciferins along with photoproteins or luciferases from sea creatures such as Aequorea, Renilla, Gaussia or Oplophorus. Central to the success of these tools are the synthetic pathways developed not only to prepare the naturally occurring luciferins, but also to design altered compounds that exhibit improved bioluminescence. Current work is indeed focused on the design of systems exhibiting extended luminescence (“glow” systems) or redshifted wavelengths, as well as constructions better adapted to conditions in cells or in vivo. This review describes the synthetic pathways used to prepare imidazo[1,2‐a]pyrazine luciferins along with the research efforts aimed at preparing analogues even better suited to the design of assays.
Drug Release Properties of a Series of Adenine‐Based Metal–Organic Frameworks
Authors: Oh Hyojae , Li Tao , An Jihyun
Published: September 2015

The drug uptake and release properties of a series of biomolecule‐based metal–organic frameworks (bMOF‐1, bMOF‐4, bMOF‐100, and bMOF‐102) have been studied. The bMOFs were loaded with the small molecule etilefrine hydrochloride and release profiles were collected in both Nanopure water and simulated body fluid (SBF). Each bMOF exhibited an initial burst of drug release at the initial stages of the experiment followed by a gradual release of the remaining drug molecules over time. bMOF‐1 released 50 % of the drug after 15 days and complete release at 80 days in SBF. bMOF‐4 released 50 % of the drug within two days and complete release at 49 days in SBF. bMOF‐100 and bMOF‐102 released 50 % of the drug after 4 h and complete release at 69 and 54 days in SBF, respectively.
Intrinsic Folding Proclivities in Cyclic β‐Peptide Building Blocks: Configuration and Heteroatom Effects Analyzed by Conformer‐Selective Spectroscopy and Quantum Chemistry
Authors: Alauddin Mohammad , Gloaguen Eric , Brenner Valérie , Tardivel Benjamin , Mons Michel , Zehnacker‐Rentien Anne , Declerck Valérie , Aitken David J.
Published: September 2015

This work describes the use of conformer‐selective laser spectroscopy following supersonic expansion to probe the local folding proclivities of four‐membered ring cyclic β‐amino acid building blocks. Emphasis is placed on stereochemical effects as well as on the structural changes induced by the replacement of a carbon atom of the cycle by a nitrogen atom. The amide A IR spectra are obtained and interpreted with the help of quantum chemistry structure calculations. Results provide evidence that the building block with a trans‐substituted cyclobutane ring has a predilection to form strong C8 hydrogen bonds. Nitrogen‐atom substitution in the ring induces the formation of the hydrazino turn, with a related but distinct hydrogen‐bonding network: the structure is best viewed as a bifurcated C8/C5 bond with the N heteroatom lone electron pair playing a significant acceptor role, which supports recent observations on the hydrazino turn structure in solution. Surprisingly, this study shows that the cis‐substituted cyclobutane ring derivative also gives rise predominantly to a C8 hydrogen bond, although weaker than in the two former cases, a feature that is not often encountered for this building block.
Oligoene‐Based π‐Helicenes or Dispiranes? Winding up Oligoyne Chains by a Multiple Carbopalladation/Stille/(Electrocyclization) Cascade
Authors: Milde Bastian , Leibeling Markus , Hecht Alexander , Jones Peter G. , Visscher Arne , Stalke Dietmar , Grunenberg Jörg , Werz Daniel B.
Published: September 2015

A domino approach consisting of up to five consecutive steps to access either highly substituted dispiranes or π‐helicenes from oligoyne chains is reported. The domino sequence consists of several carbopalladation reactions, a Stille cross‐coupling to obtain the helicenes, and, depending on the steric demands of the helicene, a final 6π‐electrocyclization to afford the dispiranes. Formally, the latter transformation contravenes the Woodward–Hoffmann rules, as revealed by X‐ray crystallography of the dispirane. Additionally, the racemization barrier of the (Z,Z,Z)‐triene‐based helicene has been determined by a kinetic analysis and compared with results from density functional theory calculations. Characteristic points on the reaction coordinate were further analyzed according to their relaxed force constants (compliance constants).
Sponge‐Like Behaviour in Isoreticular Cu(Gly‐His‐X) Peptide‐Based Porous Materials
Authors: Martí‐Gastaldo Carlos , Warren John E. , Briggs Michael E. , Armstrong Jayne A. , Thomas K. Mark , Rosseinsky Matthew J.
Published: September 2015

We report two isoreticular 3D peptide‐based porous frameworks formed by coordination of the tripeptides Gly‐L‐His‐Gly and Gly‐L‐His‐L‐Lys to CuII which display sponge‐like behaviour. These porous materials undergo structural collapse upon evacuation that can be reversed by exposure to water vapour, which permits recovery of the original open channel structure. This is further confirmed by sorption studies that reveal that both solids exhibit selective sorption of H2O while CO2 adsorption does not result in recovery of the original structures. We also show how the pendant aliphatic amine chains, present in the framework from the introduction of the lysine amino acid in the peptidic backbone, can be post‐synthetically modified to produce urea‐functionalised networks by following methodologies typically used for metal–organic frameworks built from more rigid “classical” linkers.