bluuebunny/crossref_metadata_2025 huggingface dataset:
ChemInform Abstract: Polynuclear Gold [AuI]4, [AuI]8, and Bimetallic [AuI4AgI] Complexes: C—H Functionalization of Carbonyl Compounds and Homogeneous Carbonylation of Amines.
Authors: Smirnova Ekaterina S. , Munoz Molina Jose M. , Johnson Alice , Bandeira Nuno A. G. , Bo Carles , Echavarren Antonio M.
Published: October 2016

A novel bimetallic complex BAAC is prepared and successfully applied as catalyst for the carbonylation of amines (I), (IV), and (VI).
ChemInform Abstract: Palladium‐Catalyzed Mono‐Selective ortho C—H Arylation of Aryl Sulfonamides in Water: A Concise Access to Biaryl Sulfoamide Derivatives
Authors: Liu Wei , Wang Dongyin , Zhao Yongli , Yi Fei , Chen Junmin
Published: October 2016

45 examples
ChemInform Abstract: Symmetry in Cascade Chirality‐Transfer Processes: A Catalytic Atroposelective Direct Arylation Approach to BINOL Derivatives.
Authors: Wang Jin‐Zheng , Zhou Jin , Xu Chang , Sun Hongbin , Kuerti Laszlo , Xu Qing‐Long
Published: October 2016

The reaction can be scaled up.
ChemInform Abstract: Synthesis and Application of Tetrahydro‐2H‐fluorenes by a Pd(0)‐Catalyzed Benzylic C(sp3)—H Functionalization.
Authors: Suetsugu Satoshi , Muto Nobusuke , Horinouchi Misa , Tsukano Chihiro , Takemoto Yoshiji
Published: October 2016

It is important for the construction of the desired scaffold, building block of various types of natural products, that the o‐tolyl part of the substrates bears a second o‐substituent.
ChemInform Abstract: Persulfate‐Enabled Direct C—H Alkylation of Heteroarenes with Unactivated Ethers.
Authors: McCallum Terry , Jouanno Laurie‐Anne , Cannillo Alexandre , Barriault Louis
Published: October 2016

A thermolytic potassium peroxodisulfate promoted oxidative C—H coupling of a range of N‐heterocycles with unactivated cyclic and non‐cyclic ethers is developed.
ChemInform Abstract: L‐Isoleucine Derived Bifunctional Phosphine Catalyses Asymmetric [3 + 2]‐Annulation of Allenyl‐Esters and ‐Ketones with Ketimines
Authors: Sankar Muthukumar G. , Garcia‐Castro Miguel , Golz Christopher , Strohmann Carsten , Kumar Kamal
Published: October 2016

affording a wide range of dihydropyrrolyl spirooxindoles with excellent enantioselectivities
ChemInform Abstract: Cooperative Indium(III)/Silver(I) System for Oxidative Coupling/Annulation of 1,3‐Dicarbonyls and Styrenes: Construction of Five‐Membered Heterocycles.
Authors: Ko Tae Yun , Youn So Won
Published: October 2016

A series of dihydrofurans (III), (V), and (XIII) is readily prepared by an indium‐catalyzed reaction of ketones with alkenes in the presence of Ag2O.
ChemInform Abstract: Direct Electrophilic Trifluoromethylthiolation of N‐Benzyl Indoles Using AgSCF3.
Authors: Ma Lan , Cheng Xiu‐Fen , Li Yan , Wang Xi‐Sheng
Published: October 2016

The here presented novel method for the electrophilic trifluoromethylthiolation of N‐benzylindoles uses AgSCF3 directly as the S‐CF3 source.
ChemInform Abstract: Copper‐Catalyzed Synthesis of 1,3,4‐Trisubstituted and 1,3,4,5‐Tetrasubstituted Pyrazoles via [3 + 2] Cycloadditions of Hydrazones and Nitroolefins.
Authors: Shi Chong , Ma Chaowei , Ma Haojie , Zhou Xiaoqiang , Cao Jinhui , Fan Yuxing , Huang Guosheng
Published: October 2016

The procedure tolerates a broad substrate scope for both reactants to afford the pharmaceutically interesting pyrazole units in a regioselective manner.
ChemInform Abstract: Microbial Cyclosophoraose as a Catalyst for the Synthesis of Diversified Indolyl 4H‐Chromenes via One‐Pot Three Component Reactions in Water.
Authors: Dindulkar Someshwar D. , Jeong Daham , Cho Eunae , Kim Dongjin , Jung Seunho
Published: October 2016

A cyclosophoraose is used as catalyst for the one‐pot three‐component Knoevenagel‐Michael addition‐cyclization reaction to give indolyl‐chromene derivatives.
ChemInform Abstract: An Easy Access to Fused Chromanones via Rhodium Catalyzed Oxidative Coupling of Salicylaldehydes with Heterobicyclic Olefins.
Authors: Vijayan Ajesh , Baiju T. V. , Jijy E. , Prakash Praveen , Shimi M. , Joseph Nayana , Pihko Petri M. , Varughese Sunil , Radhakrishnan K. V.
Published: October 2016

Diazabicyclic and urea‐derived bicyclic olefins react with salicylaldehydes to produce various types of fused chromanone systems of biological interest in a single step (mechanism).
ChemInform Abstract: Synthesis of 6‐Alkyl‐6H‐benzo[c]chromene Derivatives by Cyclization/Selective Ether Cleavage in One Pot: Total Synthesis of Cannabinol.
Authors: Norseeda Krissada , Tummatorn Jumreang , Krajangsri Suppachai , Thongsornkleeb Charnsak , Ruchirawat Somsak
Published: October 2016

PBr3‐mediated cyclization reactions of 1‐(2′‐alkoxybiaryl)alkanol derivatives provide access to the synthesis of a wide range of benzochromene derivatives including cannabiol precursor (VIII) in high yields.
ChemInform Abstract: Enantioselective Synthesis of 2‐Amino‐4‐(nitromethyl)‐4H‐chromene‐3‐carbonitriles from 2‐Iminochromenes.
Authors: Koz Gamze , Koz Omer , Coskun Necdet
Published: October 2016

A series of medicinally important title compounds are synthesized using enantioselective conjugate addition of nitromethane to iminochromenes.
ChemInform Abstract: Simple Broensted Acid Catalyzed C—H Functionalization: Efficient Access to Poly‐Substituted Pyridines.
Authors: Lai Shujun , Ren Xuwen , Zhao Jinzhong , Tang Zhuo , Li Guangxun
Published: October 2016

An efficient, convenient, and environmentally benign protocol for preparation of various polysubstituted pyridines under mild reaction conditions is described.
ChemInform Abstract: Pd‐Catalyzed Sequential β‐C(sp3)—H Arylation and Intramolecular Amination of δ‐C(sp2)—H Bonds for Synthesis of Quinolinones via an N,O‐Bidentate Directing Group.
Authors: Guan Mingyu , Pang Yubo , Zhang Jingyu , Zhao Yingsheng
Published: October 2016

An effective procedure for the synthesis of 2‐quinolinone derivatives by palladium‐catalyzed sequential β‐C(sp3)—H arylation and selective intramolecular C(sp2)—H/N—H amination starting with aryl iodides and carboxylic acids is reported.
ChemInform Abstract: One‐Step Synthetic Access to Isosteric and Potent Anticancer Nitrogen Heterocycles with the Benzo[c]phenanthridine Scaffold.
Authors: Steinhauer Tamara N. , Girreser Ulrich , Meier Christopher , Cushman Mark , Clement Bernd
Published: October 2016

Treatment of substrates (I), (IV) and (VIII) with various aromatic aldehydes allows the access to a library of new tetracyclic heterocycles which can be further functionalized.
ChemInform Abstract: Formal [4 + 2] Cycloaddition of Quinolines, Pyridines, and Isoquinolines with 3‐Ethoxycyclobutanones.
Authors: Onnagawa Tatsuo , Shima Yusuke , Yoshimura Tomoyuki , Matsuo Jun‐ichi
Published: October 2016

The first example of a formal [4 + 2] cycloaddition of 3‐ethoxycyclobutanones with quinolines, pyridines, and isoquinolines to give 9a‐hydro‐2H‐quinolizin‐2‐ one derivatives is reported.
ChemInform Abstract: A Reaction of 1,2‐Diamines and Aldehydes with Silyl Cyanide as Cyanide Pronucleophile to Access 2‐Aminopyrazines and 2‐Aminoquinoxalines.
Authors: Guchhait Sankar K. , Priyadarshani Garima , Gulghane Nikhil M.
Published: October 2016

The reaction proceeds through a tandem sequence of desilylation followed by Strecker reaction, amide‐forming cyclization and dehydrogenative aromatization.
ChemInform Abstract: With DBU‐Activated N‐Bromophthalimide as Potential N‐Sources to Achieve P—N Cross‐Coupling of P(O)—H Compounds.
Authors: Li Yueju , Liang Fushun
Published: October 2016

This facile method features broad phosphorous compound scope and provides phosphoramidates under mild conditions and in short reaction time.
ChemInform Abstract: New Cytotoxic and Antiinflammatory Steroids from the Soft Coral Klyxum flaccidum.
Authors: Tseng Wan‐Ru , Huang Chiung‐Yao , Tsai Yi‐Ying , Lin Yun‐Sheng , Hwang Tsong‐Long , Su Jui‐Hsin , Sung Ping‐Jyun , Dai Chang‐Feng , Sheu Jyh‐Horng
Published: October 2016

Four new steroids, klyflaccisteroids G—J, are isolated and evaluated for their biological activity.
ChemInform Abstract: 3‐Butenyloxycarbonyl as a New Hydroxyl Protecting Group in Carbohydrate Synthesis.
Authors: Zeng Nana , Niu Youhong , Ye Xin‐Shan
Published: October 2016

The 3‐butenyloxycarbonyl group can be introduced into carbohydrates such as (I) under mild conditions.
ChemInform Abstract: An Efficient Method for the Stereoselective Synthesis of N‐Substituted Trihydroxypiperidine Derivatives Promoted by p‐TsOH.
Authors: Yuan Wen , Xia Jianhui , Zhang Xiaoke , Liang Peng , Zhang Jichao , Jiao Wei , Shao Huawu
Published: October 2016

Treatment of the pentose derivatives (I) and (V) with amines and ketones is carried out in the presence of TosOH to produce N‐substituted iminosugar C‐glycosides as potential glucosidase inhibitors.
ChemInform Abstract: Asymmetric Total Syntheses of the trans‐2‐Aryl‐6‐alkyltetrahydropyrans Diospongin B and Parvistones D and E from a Common Precursor.
Authors: Li Zhilong , Tong Rongbiao
Published: October 2016

The strategy of the asymmetric total synthesis features a high‐yielding three‐step reaction sequence: Achmatowicz rearrangement, reductive γ‐deoxygenation, and Matsuda—Heck coupling to construct the rare and challenging trans‐2‐aryl‐6‐alkyltetrahydropyrans, which serve as common intermediates for the syntheses of diospongin B (I), and parvistones D (II) and E (III).
ChemInform Abstract: Thermodynamic Hydricity of Transition Metal Hydrides
Authors: Wiedner Eric S. , Chambers Matthew B. , Pitman Catherine L. , Bullock R. Morris , Miller Alexander J. M. , Appel Aaron M.
Published: October 2016

Review: 331 refs.
ChemInform Abstract: Nanoionics: Principles of Ceramic Materials Fabrication for Electrochemical Power Generation
Authors: Pervov V. S. , Ovchinnikova S. I. , Medvedeva A. E. , Makhonina E. V. , Kireeva N. V.
Published: October 2016

Review: 40 refs.
ChemInform Abstract: Recent Functionalizations of Primary Sulfonamides
Authors: Chen Yantao
Published: October 2016

Review: [256 refs.
ChemInform Abstract: Stannylation Reactions under Base Metal Catalysis: Some Recent Advances
Authors: Yoshida Hiroto
Published: October 2016

Review: [48 refs.
ChemInform Abstract: Chemical Reactions Confined within Carbon Nanotubes
Authors: Miners Scott A. , Rance Graham A. , Khlobystov Andrei N.
Published: October 2016

Review: 138 refs.
ChemInform Abstract: Cα—H Oxidations of Amines to Amides: Expanding Mechanistic Understanding and Amine Scope Through Catalyst Development
Authors: Legacy Christopher J. , Emmert Marion H.
Published: October 2016

Review: [23 refs.
ChemInform Abstract: Maleimide‐Modified Gold Nanoparticles (AuNPs): A Versatile Platform for Interfacial Click Reactions Leading to Chemically Modified AuNPs
Authors: Gobbo Pierangelo , Workentin Mark S.
Published: October 2016

Review: [30 refs.
ChemInform Abstract: Enantioselective Organocatalyzed Transformations of β‐Ketoesters
Authors: Govender Thavendran , Arvidsson Per I. , Maguire Glenn E. M. , Kruger Hendrik G. , Naicker Tricia
Published: October 2016

Review: 435 refs.
ChemInform Abstract: Chemistry of Aza‐ and Diazafulvenium Methides in Heterocyclic Synthesis
Authors: Pinho e Melo Teresa M. V. D.
Published: October 2016

Review: 42 refs.
ChemInform Abstract: Covalent or Supramolecular Combinations of Resorcinarenes and Porphyrinoids
Authors: Dumoulin Fabienne , Topkaya Derya , Yasar Songuel , Ahsen Vefa , Isci Uemit
Published: October 2016

Review: 39 refs.
ChemInform Abstract: Chemistry of 3‐Carbonyl‐2‐methyl‐4‐oxo‐4H‐l‐benzopyrans
Authors: Ghosh Chandra Kanta , Chakraborty Amarnath
Published: October 2016

Review: literature published during 1980 ‐ August 2015; 104 refs.
ChemInform Abstract: Nucleophilic Addition of Cyclopropenes
Authors: Edwards Andrew , Rubina Marina , Rubin Michael
Published: October 2016

Review: literature published in the period of 2005—2015; 85 refs.
ChemInform Abstract: An Update on the Synthesis of Pyrrolo[1,4]benzodiazepines
Authors: Varvounis George
Published: October 2016

Review: 100 refs.
ChemInform Abstract: A Niche Market of Wound Care Products and Emergence of Nanotechnology — A Short Review
Authors: Devi Nirmla , Dutta Joydeep
Published: October 2016

Review: 21 refs.
ChemInform Abstract: Photocontrol of NO, H2S, and HNO Release in Biological Systems by Using Specific Caged Compounds
Authors: Nakagawa Hidehiko
Published: October 2016

Review: 41 refs.
ChemInform Abstract: CeO2‐Encapsulated Noble Metal Nanocatalysts: Enhanced Activity and Stability for Catalytic Application
Authors: Song Shuyan , Wang Xiao , Zhang Hongjie
Published: October 2016

Review: 101 refs.
ChemInform Abstract: Hybrid Organic—Inorganic Materials Based on Polyoxometalates and Ionic Liquids and Their Application in Catalysis
Authors: Ivanova Svetlana
Published: October 2016

Review: 100 refs.
ChemInform Abstract: Synthesis and Characterization of the Lead Borate Pb6B12O21(OH)6.
Authors: Schoenegger Sandra , Ortner Teresa S. , Wurst Klaus , Heymann Gunter , Huppertz Hubert
Published: October 2016

The new title compound is synthesized by hydrothermal reaction of Pb(BO3)2, KNO3, H2O, and KOH (autoclave, 513 K, 3 d).
ChemInform Abstract: Nickel‐Catalyzed Intramolecular C—O Bond Formation: Synthesis of Cyclic Enol Ethers.
Authors: Han Seo‐Jung , Doi Ryohei , Stoltz Brian M.
Published: October 2016

A simple procedure is elaborated for the preparation of cyclic enol ethers by Ni‐catalyzed cyclization of halogenated alcohols.
ChemInform Abstract: Synthesis of Indolophanes by Photochemical Macrocyclization
Authors: Pfaffenbach Magnus , Roller Alexander , Gaich Tanja
Published: October 2016

A synthetically practical, short, and general access to novel indolophane architectures by means of a photochemical C—H activation process, the Witkop cyclization, is reported.
ChemInform Abstract: Preparation of trans‐2‐Substituted‐4‐halopiperidines and cis‐2‐Substituted‐4‐halotetrahydropyrans via AlCl3‐Catalyzed Prins Reaction.
Authors: Liu Gong‐Qing , Cui Bin , Xu Rong , Li Yue‐Ming
Published: October 2016

Whereas the title reaction between N‐tosyl homoallylamine with aryl or alkyl aldehydes and trimethylsilyl bromide, chloride or iodide delivers the corresponding 2‐substituted 4‐halopiperidines with high trans selectivity, application of trimethylsilyl fluoride provides mixtures of cis and trans isomers.
ChemInform Abstract: Stereoselective Rh‐Catalyzed Hydrogenative Desymmetrization of Achiral Substituted 1,4‐Dienes.
Authors: Fernandez‐Perez Hector , Lao Joan R. , Vidal‐Ferran Anton
Published: October 2016

A highly stereoselective desymmetrization of bis‐allylic alcohols is achieved by Rh‐catalyzed hydrogenation in the presence of TADDOL‐derived POP‐compound as optimal ligand.
ChemInform Abstract: Thermal [2 + 2]‐Cycloaddition of Ketenes with Chiral Enol Ethers: Route to Densely Substituted Cyclobutanones.
Authors: Rulliere Pauline , Grisel Julien , Poittevin Clement , Cividino Pascale , Carret Sebastien , Poisson Jean‐Francois
Published: October 2016

An unprecedented [2 + 2] cycloaddition of in situ generated ketenes with 1‐(2,4,6‐triisopropylphenyl)ethyl substituted enol ethers provides a synthesis of cyclobutanones with good to excellent diastereoselectivity.
ChemInform Abstract: Copper‐Modified Titanium Dioxide: A Simple Photocatalyst for the Chemoselective and Diastereoselective Hydrogenation of Alkynes to Alkenes under Additive‐Free Conditions.
Authors: Kominami Hiroshi , Higa Megumi , Nojima Taketo , Ito Tomohiko , Nakanishi Kousuke , Hashimoto Keiji , Imamura Kazuya
Published: October 2016

The reaction proceeds with excellent chemoselectivity and Z‐selectivity.
ChemInform Abstract: Palladium(II)‐Catalyzed Enantioselective Synthesis of α‐(Trifluoromethyl)arylmethylamines.
Authors: Johnson Thomas , Luo Bo , Lautens Mark
Published: October 2016

The enantioselective synthesis of α‐(trifluoromethyl)arylmethylamines succeeds by palladium(II)‐catalyzed addition of arylboroxines to either imines or N,O‐acetals.
ChemInform Abstract: Palladium‐Catalyzed Suzuki—Miyaura Coupling of Amides by Carbon—Nitrogen Cleavage: General Strategy for Amide N—C Bond Activation.
Authors: Meng Guangrong , Szostak Michal
Published: October 2016

A wide range of aromatic ketones (62 examples) is prepared.
ChemInform Abstract: KI‐Catalyzed α‐Acyloxylation of Acetone with Carboxylic Acids.
Authors: Wu Ya‐Dong , Huang Bei , Zhang Yue‐Xin , Wang Xiao‐Xu , Dai Jian‐Jun , Xu Jun , Xu Hua‐Jian
Published: October 2016

The scalable reaction tolerates variously functionalized aryl carboxylic acids as well as alkyl, alkenyl, and alkynyl carboxylic acids.
ChemInform Abstract: α‐Regioselective Aqueous Mukaiyama Aldol Reaction of 2‐(Trimethylsilyloxy)furan with Pyruvates.
Authors: Adamkiewicz Anna , Woyciechowska Marta , Mlynarski Jacek
Published: October 2016

A procedure that enables access to α‐(hydroxyalkyl)butenolides from 2‐(trimethylsilyloxy)furan and keto esters with excellent regiocontrol is reported.
ChemInform Abstract: Ligand Free Palladium Catalyzed Synthesis of 3‐Aryl/heteroaryl‐4‐Indolylmaleimide and Its Antimicrobial Activity.
Authors: Sharma Deepak K. , Rajput Vikrant S. , Singh Samsher , Sharma Rashmi , Khan Inshad A. , Mukherjee Debaraj
Published: October 2016

A ligand free palladium catalyzed Suzuki coupling of bromo‐indolylmaleimides with arylboronic acids at room temperature furnishes unsymmetrical arylated indolylmaleimide derivatives.
ChemInform Abstract: Stereoselective Synthesis of Thiazino[4,3‐a]indoles Using the Thia‐Pictet—Spengler Reaction of Indoles Bearing N‐Tethered Thiols and Vinylogous Thiocarbonates.
Authors: Gharpure Santosh J. , Nanda Santosh K.
Published: October 2016

An inter‐ as well as intramolecular thia‐Pictet—Spengler cyclization of N‐tethered thiols and vinylogous thiocarbonates is described for the stereoselective synthesis of N‐fused thiazinoindole derivatives.
ChemInform Abstract: Cs2CO3 as a Source of Carbonyl and Ethereal Oxygen in a Cu‐Catalyzed Cascade Synthesis of Benzofuran[3,2‐c]quinolin‐6[5‐H]ones.
Authors: Ali Wajid , Modi Anju , Behera Ahalya , Mohanta Prakash Ranjan , Patel Bhisma K.
Published: October 2016

Following the efficient title process three types of bonds are concomitantly constructed, namely two C—O one C—C and one C—N bond.
ChemInform Abstract: One‐Step Approach for the Synthesis of Functionalized Quinoxalines Mediated by T3P®—DMSO or T3P® via a Tandem Oxidation—Condensation or Condensation Reaction.
Authors: Harsha Kachigere B. , Rangappa Kanchugarkoppal S.
Published: October 2016

A cyclocondensation of 1,2‐phenylenediamines with α‐hydroxy ketones, α‐bromo ketones, or α‐diketones affords quinoxalines under simple and mild reaction conditions.
ChemInform Abstract: Selective Synthesis of Vinyl‐ or Alkynyl Chalcogenides from Glycerol and Their Water‐Soluble Derivatives.
Authors: Soares Liane K. , Silva Rafaela B. , Peglow Thiago J. , Silva Marcio S. , Jacob Raquel G. , Alves Diego , Perin Gelson
Published: October 2016

A convenient procedure is disclosed to synthesize new vinyl chalcogenides by reaction of dichalcogenides (Se, Te) with polyethylene glycol 400 as solvent.
ChemInform Abstract: Isolation and Asymmetric Total Synthesis of Perforanoid A.
Authors: Shen Yuemao , et al.
Published: October 2016

Perforanoid A (I) shows cytotoxic activity against HEL, K562, and CB3 cancer cell lines.
ChemInform Abstract: Bifunctional Chiral Dehydroalanines for Peptide Coupling and Stereoselective S‐Michael Addition.
Authors: Gutierrez‐Jimenez Marta I. , Aydillo Carlos , Navo Claudio D. , Avenoza Alberto , Corzana Francisco , Jimenez‐Oses Gonzalo , Zurbano Maria M. , Busto Jesus H. , Peregrina Jesus M.
Published: October 2016

The chiral bicyclic dehydroalanine building block (I) is applied in stereoselective S‐Michael reactions with a variety of thiols.
ChemInform Abstract: Rational Construction of Functional Molybdenum (Tungsten)—Copper—Sulfur Coordination Oligomers and Polymers from Preformed Cluster Precursors
Authors: Zhang Wen‐Hua , Ren Zhi‐Gang , Lang Jian‐Ping
Published: October 2016

Review: 162 refs.
ChemInform Abstract: Poly‐NHC Complexes of Transition Metals: Recent Applications and New Trends
Authors: Biffis Andrea , Baron Marco , Tubaro Cristina
Published: October 2016

Review: 296 refs.
ChemInform Abstract: Ynol Ethers: Synthesis and Reactivity
Authors: Verrier Charlie , Carret Sebastien , Poisson Jean‐Francois
Published: October 2016

Review: 47 refs.
ChemInform Abstract: Challenges in Catalytic Hydrophosphination
Authors: Bange Christine A. , Waterman Rory
Published: October 2016

Review: [37 refs.
ChemInform Abstract: Recent Progress in the Synthesis of Aziridine Derivatives
Authors: Jarzynski Szymon , Lesniak Stanislaw
Published: October 2016

Review: [19 refs.
ChemInform Abstract: Synthesis of Benz[d]azocines
Authors: Nevskaya Alisa A. , Voskressensky Leonid G.
Published: October 2016

Review: 16 refs.
ChemInform Abstract: Recent Developments in Selective C—H Functionalization
Authors: Frost Christopher G. , Marce Patricia , Liu Po Man
Published: October 2016

Review: latest advances in Ru(II) catalysis for ortho‐functionalization promoted by a irecting group as well as new achievements in meta‐functionalization
Modeling the Kinetics of Protein Conjugation Reactions
Authors: Pfister David , Ulmer Nicole , Klaue Antoine , Ingold Oliver , Morbidelli Massimo
Published: October 2016

Over the past decades, the pharmaceutical industry has shown a continuous infatuation for therapeutic proteins. In order to constantly improve their efficacy, chemical reactions involving the conjugation of the therapeutic protein with various chemical reagents have been developed. Little efforts have been put forth to simulate the kinetics of protein conjugation and the literature dealing with kinetic models is rather scarce as compared to the abundant references about conjugation reactions in general. In this work, techniques to measure the kinetics of reaction, model the conjugation between add‐on molecules and proteins, and evaluate the model parameters are discussed.
QUANTITATIVE ASSESSMENT OF FREE GAS BENEATH GAS HYDRATE STABILITY ZONE FROM PRESTACK SEISMIC DATA AND ROCK PHYSICS: A CASE OF HOLE NGHP01‐10A, KRISHNA‐GODAVARI BASIN, INDIA
Authors: Jin QIAN , Xiu‐Juan WANG , Dong‐Dong DONG , Shi‐Guo WU , Kalachand SAIN , Yue‐Ming YE
Published: October 2016

The distribution, saturation, and hydrate indicator of free gas beneath gas hydrate stability zone have been the difficulty in the research of gas hydrate. Amplitude versus offset (AVO) and rock physics can be used to quantitatively interpret free gas saturation. In this paper, seismic data, acquired at K‐G basin, India, are processed to preserve true amplitude information. Based on the logging data and horizon calibration, free gas saturation of NGHP01‐10A is assessed with effective medium theory and AVO modeling. It is found that free gas saturation is related to its distribution patterns. Assessments of free gas saturation in homogeneous and patchy distribution are 0.3%∼0.4% and 3%∼4%, respectively. The results show good agreement with the crossplot of Poisson's ratio which are calculated from the measurement at NGHP01‐10D. Free gas is further deduced to be homogeneous distribution on the base of dry frame Poisson's ratio with the saturation of 0.3%∼0.4%.
EDGE DETECTION OF POTENTIAL FIELD DATA USING AN ENHANCED ANALYTIC SIGNAL TILT ANGLE
Authors: Ting‐Jie YAN , Yan‐Gang WU , Yuan YUAN , Ling‐Na CHEN
Published: October 2016

Edge detection plays an important role in the interpretation of potential field data. Many traditional methods are employed to outline the edges. However, some of them cannot equalize the amplitude of the edges of shallow and deep geological bodies simultaneously; some of them although can balance the anomaly amplitude, the identified edges include some additional false edge information, especially when the measured anomalies contain both positive and negative anomalies simultaneously. Some methods used to avoid this disadvantage are subjective to some extent. In order to solve these problems, this paper proposed a new method called enhanced analytic sinal tilt angle to identify the edges of geological bodies. The new method is tested with synthetic gravity anomaly, which shows that the new method can not only identify the edges of shallow and deep geological bodies clearly and precisely, also can avoid bringing some additional false edges. Finally, we apply the new method to real measured gravity data in Sichuan basin, China, obtaining good results.
THE APPLICATION OF CEC RATIO METHOD IN THE EVALUATION OF TUFFACEOUS SANDSTONE RESERVOIRS: AN EXAMPLE IN THE X DEPRESSION OF THE HAILAR‐TAMTSAG BASIN
Authors: Bao‐Zhi PAN , Si‐Hui LIU , Bu‐Zhou HUANG , Chun‐Hui FANG , Yu‐Hang GUO
Published: October 2016

The logging evaluations of tuffaceous sandstone reservoirs are always difficult problems. The existence of tuff results in the great variations in reservoir pore structures, and the associated physical properties, which greatly influence the formation parameters. Therefore, the effects of tuff on saturation models cannot be ignored. This study took the tuffaceous sandstone reservoirs in the X depression of the Hailar‐Tamtsag Basin as an example. Based on the differences of the response characteristics between the tuff and shale, the component content was calculated using a method which combined a bacterial foraging algorithm and a particle swarm optimization algorithm. The experimental data of the cation exchange capacity (CEC) proved that the tuff had conductivity. Then, the resistivity of the tuff was obtained using the relationship between the CEC and the resistivity, which was then used to calculate the saturation. Finally, a new method was proposed to calculate the saturation of a tuffaceous sandstone reservoir, and was referred to as a CEC ratio method. The calculation results of this method were found to have a good application effect.
METHOD OF ACQUIRING HIGH QUALITY SURFACE TURBULENT FLUXES OVER THE LOESS PLATEAU
Authors: Guang‐Hui YUAN , Lei ZHANG , Yao LI , Jie‐Ning LIANG
Published: October 2016

To analyze the applicability of double rotation (DR), planar fit (PF) and fetch planar fit (FPF) over complicated terrain, turbulent data from the Semi‐Arid Climate and Environment Observatory of Lanzhou University (SACOL) are used. A parameterization scheme is provided in integral turbulent characteristics (ITC) test for SACOL data. The overall quality after data processing and quality control including sonic temperature correction, coordinate rotations, WPL correction (correction for density fluctuations), stationarity test and ITC test shows that about 45%∼62% of the total data are of high quality for friction velocity (u*), 66%∼68% for sensible heat flux, 62%∼65% for latent heat flux and 52%∼54% for CO2 flux. The proportion of the high quality of u* obtained by DR is 17% higher than PF, while the proportion of high quality data of the latter three kinds of fluxes obtained by PF is 2%∼3% higher than DR. The differences between PF and FPF are mainly in u*. Comparing the three coordinate rotations in the dominant wind direction, DR still obtains the best quality of u*. The use of DR is recommended in the complicated terrain for reducing calculation and improving the data quality.
TEMPORAL AND SPATIAL VARIATIONS OF PLASMA AND NEUTRAL VELOCITIES DURING SUBSTORM PERIODS
Authors: Ding‐Wei LIU , Hui WANG , Tao HUANG , Xue CAO , Ke‐Deng ZHANG
Published: October 2016

This study statistically investigates the temporal and spatial variations of plasma convection velocity (Vy) and thermospheric zonal wind velocity (Uy) in the range of –4 hour (h) and +2 h MLT relative to substorm onsets (MLT onset) with both CHAMP and DMSP (F13, F15) satellites observations from 2001 to 2005. It shows that Vy increase significantly in all MLT sectors and the latitudes of the peak values move equatorward in 1.5 h after substorm onsets. In the subsequent 1.5 h Vy decrease in intensity and the peaks retreat poleward, which shows that the onsets of substorm can enhance the plasma convection velocity dramatically. The relative increase of Vy is largest from –2 h to MLT onset, which indicates that the substorm mainly affects the thermosphere in the westward 0∼2 h MLT sector. Uy increases steadily in 3 hours after substorm onsets, with a 1.5 h delay relative to Vy in response to the substorm onsets.
SLIP MODEL OF THE 2001 KUNLUN MOUNTAIN MS8.1 EARTHQUAKE BY SDM: JOINT INVERSION FROM GPS AND INSAR DATA
Authors: Hong‐Wei TU , Rong‐Jiang WANG , Fa‐Qi DIAO , Yong ZHANG , Yong‐Ge WAN , Ming‐Pei JIN
Published: October 2016

For the 2001 MS8.1 Kunlun earthquake, which was one of the largest events occurred around the Tibet plateau, a large controversy still exists about its rupture detail. In this paper, we invert the co‐seismic GPS and InSAR data for a robust finite‐fault model of the Kunlun earthquake based on a realistic fault geometry buried in a layered earth structure. The inversion is based on the constrained least‐squares principle and realized using the steepest decent method (SDM). The different data sets are weighted according to their variance and spatial coverage. The results show that the slip maximum can reach up to ∼6.9 m and is located at 35.76° N and 93.40° E. The main rupture area is located at the shallow depth above 20 km. The inverted shallow slip agrees with the surface rupture observed by the field survey, and the whole slip pattern appears generally consistent with the results obtained from previous geological and seismic wave studies.
Time‐dependent risk and predictors of venous thromboembolism in breast cancer patients: A population‐based cohort study
Authors: Brand Judith S. , Hedayati Elham , Bhoo‐Pathy Nirmala , Bergh Jonas , Hall Per , Humphreys Keith , Ludvigsson Jonas F. , Czene Kamila
Published: October 2016

BACKGROUND

Venous thromboembolism (VTE) is a serious complication of cancer and its treatment. The current study assessed the risk and clinical predictors of VTE in breast cancer patients by time since diagnosis.

METHODS

This Swedish population–based study included 8338 breast cancer patients diagnosed from 2001 to 2008 in the Stockholm‐Gotland region with complete follow‐up until 2012. Their incidence of VTE was compared with the incidence among 39,013 age‐matched reference individuals from the general population. Cox and flexible parametric models were used to examine associations with patient, tumor, and treatment characteristics, accounting for time‐dependent effects.

RESULTS

Over a median follow‐up of 7.2 years, 426 breast cancer patients experienced a VTE event (cumulative incidence, 5.1%). The VTE incidence was 3‐fold increased (hazard ratio [HR], 3.28; 95% confidence interval [CI], 2.87‐3.74) in comparison with the incidence in the general population and was highest 6 months after diagnosis (HR, 8.62; 95% CI, 6.56‐11.33) with a sustained increase in risk thereafter (HR at 5 years, 2.19; 95% CI, 1.80‐2.67). Independent predictors of VTE included the following: older age, being overweight, preexisting VTE, comorbid disease, tumor size > 40 mm, progesterone receptor (PR)–negative status, more than 4 affected lymph nodes, and receipt of chemo‐ and endocrine therapy. The impact of chemotherapy was limited to early‐onset VTE, whereas comorbid disease and PR‐negative status were more strongly associated with late‐onset events.

CONCLUSIONS

This study confirms the long‐term risk of VTE in breast cancer patients and identifies a comprehensive set of clinical risk predictors. Temporal associations with patient, tumor, and treatment characteristics provide insight into the time‐dependent etiology of VTE. Cancer 2017;123:468–475. © 2016 American Cancer Society.
Difficult relationships between parents and physicians of children with cancer: A qualitative study of parent and physician perspectives
Authors: Mack Jennifer W. , Ilowite Maya , Taddei Sarah
Published: October 2016

BACKGROUND

Previous work on difficult relationships between patients and physicians has largely focused on the adult primary care setting and has typically held patients responsible for challenges. Little is known about experiences in pediatrics and more serious illness; therefore, we examined difficult relationships between parents and physicians of children with cancer.

METHODS

This was a cross‐sectional, semistructured interview study of parents and physicians of children with cancer at the Dana‐Farber Cancer Institute and Boston Children's Hospital (Boston, Mass) in longitudinal primary oncology relationships in which the parent, physician, or both considered the relationship difficult. Interviews were audiotaped, transcribed, and subjected to a content analysis.

RESULTS

Dyadic parent and physician interviews were performed for 29 relationships. Twenty were experienced as difficult by both parents and physicians; 1 was experienced as difficult by the parent only; and 8 were experienced as difficult by the physician only. Parent experiences of difficult relationships were characterized by an impaired therapeutic alliance with physicians; physicians experienced difficult relationships as demanding. Core underlying issues included problems of connection and understanding (n = 8), confrontational parental advocacy (n = 16), mental health issues (n = 2), and structural challenges to care (n = 3). Although problems of connection and understanding often improved over time, problems of confrontational advocacy tended to solidify. Parents and physicians both experienced difficult relationships as highly distressing.

CONCLUSIONS

Although prior conceptions of difficult relationships have held patients responsible for challenges, this study has found that difficult relationships follow several patterns. Some challenges, such as problems of connection and understanding, offer an opportunity for healing. However, confrontational advocacy appears especially refractory to repair; special consideration of these relationships and avenues for repairing them are needed. Cancer 2017;123:675–681. © 2016 American Cancer Society.
Nicotinic acetylcholine receptors regulate vestibular afferent gain and activation timing
Authors: Morley Barbara J. , Lysakowski Anna , Vijayakumar Sarath , Menapace Deanna , Jones Timothy A.
Published: October 2016

Little is known about the function of the cholinergic efferents innervating peripheral vestibular hair cells. We measured vestibular sensory evoked potentials (VsEPs) in α9 knockout (KO) mice, α10 KO mice, α7 KO mice, α9/10 and α7/9 double KO mice, and wild‐type (WT) controls. We also studied the morphology and ultrastructure of efferent terminals on vestibular hair cells in α9, α10, and α9/10 KOs. Both type I and type ll vestibular hair cells express the α9 and α10 subunits. The efferent boutons on vestibular cells in α9, α10, and α9/10 KOs appeared normal, but a quantitative analysis was not performed. Mean VsEP thresholds were significantly elevated in α9 and α9/10 KO animals. Some α9 and α9/10 KO animals, however, had normal or near‐normal thresholds, whereas others were greatly affected. Despite individual variability in threshold responses, latencies were consistently shortened. The double α7/9 KO resulted in decreased variance by normalizing waveforms and latencies. The phenotypes of the α7 and α10 single KOs were identical. Both α7 and α10 KO mice evidenced normal thresholds, decreased activation latencies, and larger amplitudes compared with WT mice. The data suggest a complex interaction of nicotinic acetylcholine receptors (nAChRs) in regulating vestibular afferent gain and activation timing. Although the α9/10 heteromeric nAChR is an important component of vestibular efferent activity, other peripheral or central nAChRs involving the α7 subunit or α10 subunit and α9 homomeric receptors are also important. J. Comp. Neurol. 525:1216–1233, 2017. © 2016 Wiley Periodicals, Inc.
Molecular heterogeneity of aggrecan‐based perineuronal nets around five subclasses of parvalbumin‐expressing neurons in the mouse hippocampus
Authors: Yamada Jun , Jinno Shozo
Published: October 2016

Subsets of GABAergic neurons are surrounded by perineuronal nets (PNNs), which play a critical role in the regulation of neural plasticity and neuroprotection. Although the plant lectin Wisteria floribunda agglutinin (WFA) has been commonly used to label PNNs, WFA only detects N‐acetyl‐d‐galactosamine on aggrecan, a member of the lectican family. In this study, we used WFA and the antibody against the core protein of aggrecan (ACAN) to investigate the molecular heterogeneity of aggrecan‐based PNNs around five subclasses of parvalbumin‐expressing (PV+) γ‐aminobutyric acid (GABA)ergic neurons in the CA1 and CA3 regions of the mouse hippocampus. The vast majority of ACAN+ PNNs were colocalized with WFA in the stratum pyramidale, whereas a substantial population of ACAN+ PNNs lacked WFA labeling in the stratum oriens. We then defined the subclasses of PV+ neurons based on their cellular locations, molecular expression, and septal projection. Like the WFA+ PNNs, ACAN+ PNNs surrounded PV+ basket cells and bistratified cells but not axo‐axonic cells. Unlike the WFA+ PNNs, ACAN+ PNNs frequently surrounded PV+ oriens‐lacunosum moleculare cells and hippocampo‐septal cells. Interestingly, the relative densities of GABAergic synapses were higher around PV+ neurons with ACAN+ PNNs than around those without ACAN+ PNNs. Degradation of WFA+ PNNs by chondroitinase ABC did not affect the GABAergic synaptic densities around PV+ neurons. Our findings suggest that the molecular composition of aggrecan‐based PNNs around PV+ neurons may differ in a subclass‐specific manner, and also might help determine the functional involvement of PNNs in the regulation of GABAergic synapses around PV+ neurons in the hippocampus. J. Comp. Neurol. 525:1234–1249, 2017. © 2016 Wiley Periodicals, Inc.
Whole Blood Analysis of Leukocyte‐Platelet Aggregates
Authors: Gerrits Anja J. , Frelinger Andrew L. , Michelson Alan D.
Published: October 2016

In inflammatory and thrombotic syndromes, platelets aggregate with circulating leukocytes, especially monocytes and neutrophils. This leukocyte‐platelet aggregate formation is initiated primarily through platelet surface expression of P‐selectin (CD62P), following activation‐dependent degranulation of α‐granules, binding to its constitutively expressed counter‐receptor, P‐selectin glycoprotein ligand 1 (PSGL‐1), on leukocytes. Monocyte‐platelet aggregates are a more sensitive marker of platelet activation than platelet surface P‐selectin. Detection of leukocyte‐platelet aggregates is relatively simple by whole‐blood flow cytometry. Light scatter and at least one leukocyte‐specific antibody are used to gate the desired population, and the presence of associated platelets is detected by immunostaining for abundant platelet‐specific markers. © 2016 by John Wiley & Sons, Inc.
Flow Analysis and Sorting of Plant Chromosomes
Authors: Vrána Jan , Cápal Petr , Šimková Hana , Karafiátová Miroslava , Čížková Jana , Doležel Jaroslav
Published: October 2016

Analysis and sorting of plant chromosomes (plant flow cytogenetics) is a special application of flow cytometry in plant genomics and its success depends critically on sample quality. This unit describes the methodology in a stepwise manner, starting with the induction of cell cycle synchrony and accumulation of dividing cells in mitotic metaphase, and continues with the preparation of suspensions of intact mitotic chromosomes, flow analysis and sorting of chromosomes, and finally processing of the sorted chromosomes. Each step of the protocol is described in detail as some procedures have not been used widely. Supporting histograms are presented as well as hints on dealing with plant material; the utility of sorted chromosomes for plant genomics is also discussed. © 2016 by John Wiley & Sons, Inc.
Coalition structure generation problems: optimization and parallelization of the IDP algorithm in multicore systems
Authors: Cruz Francisco , Espinosa Antonio , Moure Juan C. , Cerquides Jesus , Rodriguez‐Aguilar Juan A. , Svensson Kim , Ramchurn Sarvapali D.
Published: October 2016

The coalition structure generation problem is well known in the area of multi‐agent systems. Its goal is to establish coalitions between agents while maximizing the global welfare. Among the existing different algorithms designed to solve the coalition structure generation problem, DP and IDP are the ones with smaller temporal complexity. After analyzing the operation of the dynamic programming and improved dynamic programming algorithms, we have identified which are the most frequent operations and propose an optimized method. In addition, we study and implement a method for dividing the work into different threads. To describe incremental improvements of the algorithm design, we first compare performance of an improved single central processing unit core version where we obtain speedups ranging from 7 ×  to 11 × . Then, we describe the best resource use in a multi‐thread optimized version where we obtain an additional 7.5 ×  speedup running in a 12‐core machine.
Acylglycine Analysis by Ultra‐Performance Liquid Chromatography‐Tandem Mass Spectrometry (UPLC‐MS/MS)
Authors: Hobert Judith A. , Liu Aiping , Pasquali Marzia
Published: October 2016

Quantitative analysis of urine acylglycines has shown to be a highly sensitive and specific method with proven clinical utility for the diagnosis of several inherited metabolic disorders including: medium chain acyl‐CoA dehydrogenase deficiency, multiple acyl‐CoA dehydrogenase deficiency, short chain acyl‐CoA dehydrogenase deficiency, 3‐methylcrotonyl‐CoA carboxylase deficiency, 2‐methylbutyryl‐CoA dehydrogenase deficiency, isovaleric acidemia, propionic academia, and isobutyryl‐CoA dehydrogenase deficiency. Here, a method that is currently performed using ultra‐performance liquid chromatography/tandem mass spectrometry (UPLC‐MS/MS) is described. © 2016 by John Wiley & Sons, Inc.
Direct Electron Transfer of Cellobiose Dehydrogenase on Positively Charged Polyethyleneimine Gold Nanoparticles
Authors: Tavahodi Mojtaba , Ortiz Roberto , Schulz Christopher , Ekhtiari Ali , Ludwig Roland , Haghighi Behzad , Gorton Lo
Published: October 2016

Efficient conjugation between biomolecules and electrode materials is one of the main challenges in the field of biosensors. Cellobiose dehydrogenase (CDH) is a monomeric enzyme, which consists of two separate domains: one catalytic dehydrogenase domain (DHCDH) carrying strongly bound flavin adenine dinucleotide (FAD) in the active site and a cytochrome domain (CYTCDH) carrying a b‐type heme connected by a flexible linker region. Herein, we report on the development of a lactose biosensor, based on direct electron transfer (DET) from CDH from Phanerochaete sordida (PsCDH) electrostatically attached onto polyethyleneimine‐stabilized gold nanoparticles (PEI@AuNPs) used to cover a conventional polycrystalline solid gold disk electrode. PEI@AuNPs were synthesized in aqueous solution using PEI as reducing agent for AuIII and as stabilizer for the nanoparticles. The heterogeneous electron‐transfer (ET) rate (ks) for the redox reaction of immobilized PsCDH at the modified electrodes was calculated based on the Laviron theory and was found to be (39.6±2.5) s−1. The proposed lactose biosensor exhibits good long term stability as well as high and reproducible sensitivity to lactose with a response time less than 5 s and a linear range from 1 to 100 μm.
Synthesis of Cross‐linked Ionic Poly(styrenes) and their Application as Catalysts for the Synthesis of Carbonates from CO2 and Epoxides
Authors: Bobbink Felix D. , Van Muyden Antoine P. , Gopakumar Aswin , Fei Zhaofu , Dyson Paul J.
Published: October 2016

A series of dicationic styrene‐functionalized imidazolium‐based salts, in which the two imidazolium rings are bridged by a functionalized spacer, are prepared. The salts are polymerized to afford cross‐linked imidazolium‐based ionic polystyrene materials, which, owing to the presence of the functionalized spaces, should be highly active organocatalysts for the cycloaddition of CO2 to epoxides to afford cyclic carbonates (CCE reaction). The catalytic activities of the polymers are evaluated in the CCE reaction. The most active catalyst incorporates a diol functionality and is active at 80 °C and a pressure of 4 bar at a loading of 5 mol %, which is comparable to the most active organocatalysts. Moreover, high yields can be obtained under atmospheric pressure upon increasing the temperature to 120 °C. Under harsher conditions, the catalyst is highly active at a loading one order of magnitude lower, highlighting the importance of benchmark conditions for the CCE reaction. Moreover, the polymer catalysts are advantageous because they can be used at low catalyst loadings, the carbonate product is easily isolated in pure form, and loss of activity of the recovered polymer catalyst is not observed during reuse.
Protein Interaction Profile Sequencing (PIP‐seq)
Authors: Foley Shawn W. , Gregory Brian D.
Published: October 2016

Every eukaryotic RNA transcript undergoes extensive post‐transcriptional processing from the moment of transcription up through degradation. This regulation is performed by a distinct cohort of RNA‐binding proteins which recognize their target transcript by both its primary sequence and secondary structure. Here, we describe protein interaction profile sequencing (PIP‐seq), a technique that uses ribonuclease‐based footprinting followed by high‐throughput sequencing to globally assess both protein‐bound RNA sequences and RNA secondary structure. PIP‐seq utilizes single‐ and double‐stranded RNA‐specific nucleases in the absence of proteins to infer RNA secondary structure. These libraries are also compared to samples that undergo nuclease digestion in the presence of proteins in order to find enriched protein‐bound sequences. Combined, these four libraries provide a comprehensive, transcriptome‐wide view of RNA secondary structure and RNA protein interaction sites from a single experimental technique. © 2016 by John Wiley & Sons, Inc.
Isolation of Primary Fibroblast Culture from Wildlife: the Panthera onca Case to Preserve a South American Endangered Species
Authors: Mestre‐Citrinovitz Ana Cecilia , Sestelo Adrián Jorge , Ceballos María Belén , Barañao José Lino , Saragüeta Patricia
Published: October 2016

Cell line establishment of somatic cells is a valuable resource to preserve genetic material of rare, difficult‐to‐find, endangered and giant species like Jaguar (Panthera onca), the largest South American felid. This unit focuses on the isolation and culture of fibroblasts from Jaguar skin and muscle biopsies, and ear cartilage dissection immediately after death to preserve one of the several endangered species in this biome. These culture techniques enabled us to contribute 570 samples from 45 autochthonous and endangered species, including Jaguar. The fibroblasts obtained are a part of the Genetic Bank of Buenos Aires Zoo with the 6700 samples, including tissues such as muscle, ovarian, testicular, blood, fibroblast cultures, sperm, hair, and fluids and cells from 450 individuals of 87 different species. © 2016 by John Wiley & Sons, Inc.
GILA, a Replacement for the Soft‐Agar Assay that Permits High‐Throughput Drug and Genetic Screens for Cellular Transformation
Authors: Izar Benjamin , Rotem Asaf
Published: October 2016

For the last five decades, measuring the ability of cells to grow in soft agar has served as the gold standard assay for in vitro cellular transformation. Nevertheless, the soft agar colony formation assay is time consuming and ill‐suited for high‐throughput screens. This unit describes an equally qualitative and quantitative assay known as growth in low attachment or GILA. The GILA assay is suitable for high‐throughput pharmacological or genetic screens and allows the simultaneous examination of multiple cell lines and experimental perturbations. GILA conditions are specific and relevant to the transformed state because they depend on a property of cancer cells that is not shared by non‐transformed cells. The GILA assay enables ex vivo drug sensitivity testing of patient‐derived tumor cells to define precise treatments for individual patients. © 2016 by John Wiley & Sons, Inc.