bluuebunny/crossref_metadata_2025 huggingface dataset:
Sustainable Catalysis: Rational Pd Loading on MIL‐101Cr‐NH2 for More Efficient and Recyclable Suzuki–Miyaura Reactions
Authors: Pascanu Vlad , Yao Qingxia , Bermejo Gómez Antonio , Gustafsson Mikaela , Yun Yifeng , Wan Wei , Samain Louise , Zou Xiaodong , Martín‐Matute Belén
Published: November 2013

Palladium nanoparticles have been immobilized into an amino‐functionalized metal–organic framework (MOF), MIL‐101Cr‐NH2, to form Pd@MIL‐101Cr‐NH2. Four materials with different loadings of palladium have been prepared (denoted as 4‐, 8‐, 12‐, and 16 wt %Pd@MIL‐101Cr‐NH2). The effects of catalyst loading and the size and distribution of the Pd nanoparticles on the catalytic performance have been studied. The catalysts were characterized by using scanning electron microscopy (SEM), transmission electron microscopy (TEM), Fourier‐transform infrared (FTIR) spectroscopy, powder X‐ray diffraction (PXRD), N2‐sorption isotherms, elemental analysis, and thermogravimetric analysis (TGA). To better characterize the palladium nanoparticles and their distribution in MIL‐101Cr‐NH2, electron tomography was employed to reconstruct the 3D volume of 8 wt %Pd@MIL‐101Cr‐NH2 particles. The pair distribution functions (PDFs) of the samples were extracted from total scattering experiments using high‐energy X‐rays (60 keV). The catalytic activity of the four MOF materials with different loadings of palladium nanoparticles was studied in the Suzuki–Miyaura cross‐coupling reaction. The best catalytic performance was obtained with the MOF that contained 8 wt % palladium nanoparticles. The metallic palladium nanoparticles were homogeneously distributed, with an average size of 2.6 nm. Excellent yields were obtained for a wide scope of substrates under remarkably mild conditions (water, aerobic conditions, room temperature, catalyst loading as low as 0.15 mol %). The material can be recycled at least 10 times without alteration of its catalytic properties.
Pd‐Catalyzed Carbonylative α‐Arylation of Aryl Bromides: Scope and Mechanistic Studies
Authors: Nielsen Dennis U. , Lescot Camille , Gøgsig Thomas M. , Lindhardt Anders T. , Skrydstrup Troels
Published: November 2013

Reaction conditions for the three‐component synthesis of aryl 1,3‐diketones are reported applying the palladium‐catalyzed carbonylative α‐arylation of ketones with aryl bromides. The optimal conditions were found by using a catalytic system derived from [Pd(dba)2] (dba=dibenzylideneacetone) as the palladium source and 1,3‐bis(diphenylphosphino)propane (DPPP) as the bidentate ligand. These transformations were run in the two‐chamber reactor, COware, applying only 1.5 equivalents of carbon monoxide generated from the CO‐releasing compound, 9‐methylfluorene‐9‐carbonyl chloride (COgen). The methodology proved adaptable to a wide variety of aryl and heteroaryl bromides leading to a diverse range of aryl 1,3‐diketones. A mechanistic investigation of this transformation relying on 31P and 13C NMR spectroscopy was undertaken to determine the possible catalytic pathway. Our results revealed that the combination of [Pd(dba)2] and DPPP was only reactive towards 4‐bromoanisole in the presence of the sodium enolate of propiophenone suggesting that a [Pd(dppp)(enolate)] anion was initially generated before the oxidative‐addition step. Subsequent CO insertion into an [Pd(Ar)(dppp)(enolate)] species provided the 1,3‐diketone. These results indicate that a catalytic cycle, different from the classical carbonylation mechanism proposed by Heck, is operating. To investigate the effect of the dba ligand, the Pd0 precursor, [Pd(η3‐1‐PhC3H4)(η5‐C5H5)], was examined. In the presence of DPPP, and in contrast to [Pd(dba)2], its oxidative addition with 4‐bromoanisole occurred smoothly providing the [PdBr(Ar)(dppp)] complex. After treatment with CO, the acyl complex [Pd(CO)Br(Ar)(dppp)] was generated, however, its treatment with the sodium enolate led exclusively to the acylated enol in high yield. Nevertheless, the carbonylative α‐arylation of 4‐bromoanisole with either catalytic or stoichiometric [Pd(η3‐1‐PhC3H4)(η5‐C5H5)] over a short reaction time, led to the 1,3‐diketone product. Because none of the acylated enol was detected, this implied that a similar mechanistic pathway is operating as that observed for the same transformation with [Pd(dba)2] as the Pd source.
ChemInform Abstract: LuF[SeO3]: Structural Chameleon of Lanthanoid Fluoride Oxoselenates(IV).
Authors: Lipp Christian , Dinnebier Robert E. , Schleid Thomas
Published: November 2013

The title compound is synthesized by solid state reaction of Lu2O3, LuF3, and SeO2 using CsBr as a flux (750 °C, 5 d).
ChemInform Abstract: Crystal Structure, Phase Transitions, and Magnetic Properties of Iridium Perovskites Sr2MIrO6 (M: Ni, Zn).
Authors: Kayser P. , Martinez‐Lope M. J. , Alonso J. A. , Retuerto M. , Croft M. , Ignatov A. , Fernandez‐Diaz M. T.
Published: November 2013

The title compounds are prepared by high oxygen pressure/high temp.
ChemInform Abstract: Room‐Temperature Synthesis of Flower‐Like BiOX (X: Cl, Br, I) Hierarchical Structures and Their Visible‐Light Photocatalytic Activity.
Authors: Yin Shuang‐Feng , et al. et al.
Published: November 2013

The three‐dimensional flower‐like hierarchical title materials are synthesized from Bi(NO3)3 and L‐lysine dissolved in aqueous HX (X: Cl, Br, I) at pH 9 adjusted with aq.
ChemInform Abstract: Enantioselective Cycloaddition of Carbonyl Ylides with Arylallenes Using Rh2(S‐TCPTTL)4.
Authors: Krishnamurthi Janagiraman , Nambu Hisanori , Takeda Koji , Anada Masahiro , Yamano Akihito , Hashimoto Shunichi
Published: November 2013

The first catalytic asymmetric cycloaddition of carbonyl ylides, derived from diazoketoesters (I), with arylallenes (II) proceeds in a fully chemo‐ and regioselective manner to give 8‐oxabicyclo[3.2.1]octanes (III) (18 examples) with excellent enantio‐ and exo‐diastereoselectivity.
ChemInform Abstract: Radical‐Based Regioselective C—H Functionalization of Electron‐Deficient Heteroarenes: Scope, Tunability, and Predictability.
Authors: O'Hara Fionn , Blackmond Donna G. , Baran Phil S.
Published: November 2013

The authors establish guidelines for the title reaction based on systematic investigations.
ChemInform Abstract: One‐Step Stereoselective Synthesis of Trisubstituted Monofluoroalkenes from 3,3,3‐Trifluoropropionates.
Authors: Lecea Mercedes , Grassin Adrien , Ferreiro‐Mederos Leticia , Choppin Sabine , Urbano Antonio , Carreno M. Carmen , Colobert Francoise
Published: November 2013

An access towards highly functionalized monofluoroalkenes is presented by the reaction of trifluoropropionates and Li or Mg nucleophiles.
ChemInform Abstract: Selective Reduction of Esters to Aldehydes under the Catalysis of Well‐Defined NHC‐Iron Complexes.
Authors: Li Haoquan , Castro Luis C. Misal , Zheng Jianxia , Roisnel Thierry , Dorcet Vincent , Sortais Jean‐Baptiste , Darcel Christophe
Published: November 2013

It provides a mild and efficient approach to aliphatic and aromatic aldehydes.
ChemInform Abstract: Iridium‐Catalyzed Enantioselective Hydrogenation of α,β‐Unsaturated Carboxylic Acids with Tetrasubstituted Olefins.
Authors: Song Song , Zhu Shou‐Fei , Li Yu , Zhou Qi‐Lin
Published: November 2013

The title methodology allows the preparation of chiral α‐substituted carboxylic acids in excellent yields and enantioselectivities.
ChemInform Abstract: Iron‐Catalyzed Three‐Component Reaction: Multiple C—C Bond Cleavages and Reorganizations.
Authors: Wang Peng , Liao Saihu , Zhu Jian‐Bo , Tang Yong
Published: November 2013

A novel iron‐catalyzed C‐C bond cleavage and reorganization process is developed consisting of a three component reaction of crotonate derived phosphorous ylides (I), methyl diazoacetate (II) and a variety of α‐bromoacetophenones (III).
ChemInform Abstract: A Continuous Flow Solution to Achieving Efficient Aerobic anti‐Markovnikov Wacker Oxidation.
Authors: Bourne S. L. , Ley S. V.
Published: November 2013

An optimized continuous flow process is described to convert styrenes to aryl acetaldehydes using a Pd/Cu‐catalyzed anti‐Markovnikov addition of water followed by a Wacker‐type oxidation.
ChemInform Abstract: Domino Synthesis of Fluorine‐Substituted Polycyclic Aromatic Hydrocarbons: 1,1‐Difluoroallenes as Synthetic Platforms.
Authors: Fuchibe Kohei , Mayumi Yuka , Zhao Nan , Watanabe Shumpei , Yokota Misaki , Ichikawa Junji
Published: November 2013

This is a novel method for generating allylic CF2 cations from 1,1‐difluoroallenes with an indium(III) catalyst.
ChemInform Abstract: Arene C—H Bond Functionalization Coupling with Cyclization of Allenes.
Authors: Zeng Rong , Ye Juntao , Fu Chunling , Ma Shengming
Published: November 2013

A rhodium(III)‐catalyzed reaction of N‐methoxybenzamides with tri‐ and tetrasubstituted 2,3‐allenols is developed to yield highly substituted 2,5‐dihydrofurans (III) and (VI).
ChemInform Abstract: Formation of Highly Functionalized Thiophenes by Reaction of Tetramethylthiourea, Acetylenic Esters, and α‐Haloketones.
Authors: Yavari Issa , Malekafzali Alaleh
Published: November 2013

Addition of tetramethylthiourea (III) to dialkyl acetylenedicarboxylate (I) generates 1:1 zwitterionic intermediates which are trapped by α‐haloketones (II) to afford the functionalized thiophenes (IV).
ChemInform Abstract: Synthesis of Azetidines and Pyrrolidines via Iodocyclization of Homoallyl Amines and Exploration of Activity in a Zebrafish Embryo Assay.
Authors: Fossey John S. , et al. et al.
Published: November 2013

A synthetically versatile protocol for the stereospecific cyclization of homoallyl amine derivatives (I) to deliver cis‐azetidines (III) and cis‐ or trans‐pyrrolidine derivatives (V)—(IX) is developed.
ChemInform Abstract: Asymmetric Synthesis and Molecular Docking Study of Enantiomerically Pure Pyrrolidine Derivatives with Potential Antithrombin Activity.
Authors: Ayan Seylan , Dogan Oezdemir , Ivantcova Polina M. , Datsuk Nikita G. , Shulga Dmitry A. , Chupakhin Vladimir I. , Zabolotnev Dmitry V. , Kudryavtsev Konstantin V.
Published: November 2013

Both enantiomers of pyrrolidine (III) are readily prepared by a zinc‐catalyzed asymmetric 1,3‐dipolar cycloaddition of tert‐butyl acrylate (II) with aldimine (I).
ChemInform Abstract: Bromophenyl Substituted Dithiafulvenes and Tetrathiafulvalene Vinylogues: Synthesis, Structure, and Electronic Properties.
Authors: Bouzan Stephen , Dawe Louise N. , Zhao Yuming
Published: November 2013

Oxidative dimerization of readily prepared bromophenyl substituted dithiafulvalenes (IIIa,b) offers a convenient synthesis of bis(bromophenyl) substituted tetrathiafulvalene vinylogues.
ChemInform Abstract: A New and Direct Route to 3‐Fluoromethyl Substituted Pyrazol‐4‐acrylates via Pd‐Catalyzed C—H Activation.
Authors: Wang Xiaoguang , Fang Xiang , Xiao Hongyuan , Gong Dongming , Yang Xueyan , Wu Fanhong
Published: November 2013

The first example of oxidative olefination via Pd‐catalyzed C4‐H activation of CF3‐ and CF2H‐substituted pyrazoles is reported.
ChemInform Abstract: Synthesis of Bis‐spirofused Thiapyrrolizidinooxindoles by 1,3‐Dipolar Cycloaddition
Authors: Shvets A. A. , Nelyubina Yu. V. , Lyssenko K. A. , Kurbatov S. V.
Published: November 2013

of arylidene derivatives of rhodanine with azomethine ylide generated in situ from isatin and thiaproline
ChemInform Abstract: Five‐Fold Symmetric Penta‐Substituted Corannulene with Gelation Properties and a Liquid‐Crystalline Phase.
Authors: Mattarella Martin , Haberl Johannes M. , Ruokolainen Janne , Landau Ehud M. , Mezzenga Raffaele , Siegel Jay S.
Published: November 2013

Compounds Ia‐c are prepared in a three step sequence.
ChemInform Abstract: Synthesis, Anticancer Activity and Photophysical Properties of Novel Substituted 2‐Oxo‐2H‐chromenylpyrazolecarboxylates.
Authors: Kumar J. Ashok , Saidachary G. , Mallesham G. , Sridhar B. , Jain Nishant , Kalivendi Shashi Vardhan , Rao V. Jayathirtha , Raju B. China
Published: November 2013

Title compounds (III) and (V) are synthesized by [3 + 2] cycloaddition of hydrazones (I) and (IV) with acetylenedicarboxylic ester (II), respectively.
ChemInform Abstract: Diversity‐Oriented General Protocol for the Synthesis of Privileged Oxygen Scaffolds: Pyrones, Coumarins, Benzocoumarins and Naphthocoumarins.
Authors: Goel Atul , Taneja Gaurav , Raghuvanshi Ashutosh , Kant Ruchir , Maulik Prakas R.
Published: November 2013

Title compounds such as (IV), (VIII), and (XIII) are prepared through carbanion‐induced ring transformation of lactones such as (I), (V), and (X) with various methylene carbonyl compounds such as (II) and (VI), followed by DDQ‐mediated unprecedented oxidative cleavage of the C—C double bond.
ChemInform Abstract: A Catalytic Michael/Horner—Wadsworth—Emmons Cascade Reaction for Enantioselective Synthesis of Thiochromenes.
Authors: Choudhury Abhijnan Ray , Mukherjee Santanu
Published: November 2013

An enantioselective sulfa‐Michael/Horner—Wadsworth—Emmons reaction cascade is developed using a bifunctional urea catalyst.
ChemInform Abstract: Copper‐Catalyzed Enantioselective Intramolecular N‐Arylation, an Efficient Method for Kinetic Resolution.
Authors: Yang Wenqiang , Long Yan , Zhang Shasha , Zeng Youlin , Cai Qian
Published: November 2013

Kinetic resolution by copper‐catalyzed N‐arylation is reported for the first time.
ChemInform Abstract: Synthesis and Structure of New Imidazo‐ and Pyrazolo[5,1‐d][1,2,3,5]thiatriazines Based on the Reaction of Diazoazoles with Acyl Isothiocyanates Controlled by S···O Interaction.
Authors: Sadchikova Elena V. , Bakulev Vasiliy A. , Subbotina Julia O. , Privalova Darya L. , Dehaen Wim , Van Hecke Kristof , Robeyns Koen , Van Meervelt Luc , Mokrushin Vladimir S.
Published: November 2013

Cycloaddition reactions of 5‐diazopyrazoles and 5‐diazoimidazoles with acyl isothiocyanates give thiatriazine derivatives.
ChemInform Abstract: Antimicrobial and Antioxidant Isoflavonoid Derivatives from the Roots of Amphimas pterocarpoides.
Authors: Saah Edwige P. Fodja , Sielinou Valerie Tedjon , Kuete Victor , Lacmata Stephen T. , Nkengfack Augustin E.
Published: November 2013

isolation and structure elucidation of amphiisoflavone (I)
ChemInform Abstract: An Approach to Hyperolactone C and Analogues Using Late Stage Conjugate Addition on an Oxonium Ylide‐Derived Spirofuranone.
Authors: Hodgson David M. , Moreno‐Clavijo Elena , Day Sophie E. , Man Stanislav
Published: November 2013

A stereocontrolled approach to spirolactone (III) is described.
ChemInform Abstract: Carbon Nanotube‐Based Heterostructures for Solar Energy Applications
Authors: Wang Lei , Liu Haiqing , Konik Robert M. , Misewich James A. , Wong Stanislaus S.
Published: November 2013

Review: 152 refs.
ChemInform Abstract: Gas Sensors Based on One Dimensional Nanostructured Metal‐Oxides: A Review
Authors: Arafat M. M. , Dinan B. , Akbar Sheikh A. , Haseeb A. S. M. A.
Published: November 2013

Review: 106 refs.
ChemInform Abstract: Stereocontrolled Total Synthesis of Natural Products with Characteristic Molecular Structures and Biological Activities
Authors: Shishido Kozo
Published: November 2013

Review: 89 refs.
ChemInform Abstract: Molecular Chirality in Chemistry and Biology: Historical Milestones
Authors: Gal Joseph
Published: November 2013

Review: <175 refs.
ChemInform Abstract: A New Family of Multiple‐Bond Compounds Between Heavier Group 14 Elements
Authors: Sasamori Takahiro , Tokitoh Norihiro
Published: November 2013

Review: 93 refs.
ChemInform Abstract: Guidelines for Radical Reactions: Some Thirty Years on
Authors: Hancock Amber N. , Schiesser Carl H.
Published: November 2013

Review: 29 refs.
ChemInform Abstract: Superposition, Entanglement, and Raising Schroedinger′s Cat (Nobel Lecture)
Authors: Wineland David J.
Published: November 2013

Review: 163 refs.
ChemInform Abstract: From Symmetric to Asymmetric Design of Bio‐Inspired Smart Single Nanochannels
Authors: Zhang Huacheng , Tian Ye , Jiang Lei
Published: November 2013

Review: 104 refs.
ChemInform Abstract: Metal—Organic Frameworks as a Tunable Platform for Designing Functional Molecular Materials
Authors: Wang Cheng , Liu Demin , Lin Wenbin
Published: November 2013

Review: 82 refs.
ChemInform Abstract: Poly(2‐oxazoline) Functionalized Surfaces: From Modification to Application
Authors: Tauhardt Lutz , Kempe Kristian , Gottschaldt Michael , Schubert Ulrich S.
Published: November 2013

Review: different approaches to immobilize the title biocompatible polymers on surfaces as well as properties and applications; 50 refs.
ChemInform Abstract: Electronic CD Exciton Chirality Method: Principles and Applications
Authors: Harada Nobuyuki , Nakanishi Koji , Berova Nina
Published: November 2013

Review: 180 refs.
Synthesis and Biological Evaluation of Biphenyl Amides That Modulate the US28 Receptor
Authors: Kralj Ana , Kurt Elif , Tschammer Nuska , Heinrich Markus R.
Published: November 2013

To prepare and biologically evaluate 38 new potential US28 allosteric modulators, we employed a straightforward synthetic route involving radical arylation. The study was based on a former lead structure but with the dihydroisoquinolinone moiety replaced by substituted biphenyls. The investigation of structure–activity relationships among the new biphenyl‐derived ligands led to a preliminary pharmacophore model and the discovery of four promising candidates with full inverse agonist properties.
Energy Relay from an Unconventional Yellow Dye to CdS/CdSe Quantum Dots for Enhanced Solar Cell Performance
Authors: Narayanan Remya , Das Amrita , Deepa Melepurath , Srivastava Avanish Kumar
Published: November 2013

A new design for a quasi‐solid‐state Forster resonance energy transfer (FRET) enabled solar cell with unattached Lucifer yellow (LY) dye molecules as donors and CdS/CdSe quantum dots (QDs) tethered to titania (TiO2) as acceptors is presented. The Forster radius is experimentally determined to be 5.29 nm. Sequential energy transfer from the LY dye to the QDs and electron transfer from the QDs to TiO2 is followed by fluorescence quenching and electron lifetime studies. Cells with a donor–acceptor architecture (TiO2/CdS/CdSe/ZnS‐LY/S2−‐multi‐walled carbon nanotubes) show a maximum incident photon‐to‐current conversion efficiency of 53 % at 530 nm. This is the highest efficiency among Ru‐dye free FRET‐enabled quantum dot solar cells (QDSCs), and is much higher than the donor or acceptor‐only cells. The FRET‐enhanced solar cell performance over the majority of the visible spectrum paves the way to harnessing the untapped potential of the LY dye as an energy relay fluorophore for the entire gamut of dye sensitized, organic, or hybrid solar cells.
Double‐Wall Carbon Nanotube–Porphyrin Supramolecular Hybrid: Synthesis and Photophysical Studies
Authors: Vizuete María , Gómez‐Escalonilla María J. , Fierro José Luis G. , Atienzar Pedro , García Hermenegildo , Langa Fernando
Published: November 2013

Double‐wall carbon nanotubes (DWCNTs) with pyridyl units covalently attached to the external wall through isoxazolino linkers and carboxylic groups that have been esterified by pentyl chains are synthesized. The properties of these modified DWCNTs are then compared with an analogous sample based on single‐wall carbon nanotubes (SWCNTs). Raman spectroscopy shows the presence of characteristic radial breathing mode vibrations, confirming that the samples partly retain the integrity of the nanotubes in the case of DWCNTs, including the internal and external nanotubes. Quantification of the pyridyl content for both samples (DWCNT and SWCNT derivatives) is based on X‐ray photoelectron spectroscopy and thermogravimetric profiles, showing very similar substituent load. Both pyridyl‐containing nanotubes (DWCNTs and SWCNTs) form a complex with zinc porphyrin (ZnP), as evidenced by the presence of two isosbestic points in the absorption spectra of the porphyrin upon addition of the pyridyl‐functionalized nanotubes. Supramolecular complexes based on pyridyl‐substituted DWCNTs and SWCNTs quench the emission and the triplet excited state identically, through an energy‐transfer mechanism based on pre‐assembly of the ground state. Thus, the presence of the intact inner wall in DWCNTs does not influence the quenching behavior, with respect to SWCNTs, for energy‐transfer quenching with excited ZnP. These results sharply contrast with previous ones referring to electron‐transfer quenching, in which the double‐wall morphology of the nanotubes has been shown to considerably reduce the lifetime of charge separation, owing to faster electron mobility in DWCNTs compared to SWCNTs.
Cochrane in context: Vaccines for measles, mumps and rubella in children
Authors: Demicheli Vittorio , Rivetti Alessandro , Debalini Maria Grazia , Di Pietrantonj Carlo , Robinson Joan
Published: November 2013

Cochrane Review: Vaccines for measles, mumps and rubella in children Demicheli V, Rivetti A, Debalini MG, Di Pietrantonj C. Vaccines for measles, mumps and rubella in children. Cochrane Database of Systematic Reviews 2012, Issue 2. Art. No.: CD004407. DOI: 10.1002/14651858.CD004407.pub3

This companion piece to the review, “Vaccines for measles, mumps and rubella in children,” contains the following pieces:

The abstract of the review

A commentary from one or more of the review authors, explaining why the review team felt the review was an important one to produce

A commentary from Joan Robinson, Editor‐in‐chief, outlining the review's findings

A review of clinical practice guidelines from the American Academy of Pediatrics, the Canadian Paediatric Society and the National Institute for Health and Care Excellence (NICE), United Kingdom

Some other recently published references on this topic
Catalytic Asymmetric Synthesis of Dihydrofurans and Cyclopentenols with Tertiary Stereocenters
Authors: Wu Zhongtao , Madduri Ashoka V. R. , Harutyunyan Syuzanna R. , Minnaard Adriaan J.
Published: November 2013

A new asymmetric synthesis of dihydrofurans and cyclopentenols has been developed and is based on the copper‐catalyzed 1,2‐addition of Grignard reagents to enones in combination with Sonogashira coupling/cyclization or ring‐closing metathesis. By this approach, dihydrofurans with an oxygen‐containing tertiary stereocenter and chiral tertiary cyclopentenols are efficiently prepared. The absolute stereochemistry of the products has been established.
Effects of Cylindrospermopsis raciborskii (cyanobacteria) on the swimming behavior of Daphnia (cladocera)
Authors: Ferrão-Filho Aloysio S. , Soares Maria Carolina S. , Lima Ramon S. , Magalhães Valeria F.
Published: November 2013

The present study aimed to test the effects of raw water samples from a eutrophic reservoir and of a saxitoxin-producing strain of Cylindrospermopsis raciborskii on the swimming behavior of 2 key herbivore species of Daphnia. Two complementary approaches were used, acute bioassays and behavioral assays using an automated movement tracking system for measuring the following activity parameters: swimming time, resting time, distance traveled, and mean velocity. In both assays, animals were exposed to field samples or to toxic filaments in different concentrations and observed for 2 h to 3 h. In the acute bioassays, there was a decrease in the number of swimming individuals during the exposure period and a recovery following removal from toxic algae. A significant relationship was found between median effective concentration and the saxitoxin content of seston (r2 = 0.998; p = 0.025) in the acute bioassays with raw water samples. Behavioral assays also showed significant effects in the activity parameters with both field samples and the strain of C. raciborskii, with some recovery during the exposure period. Both approaches corroborated previous research on the effects of neurotoxic C. raciborskii on the swimming activity of Daphnia, and these effects are compatible with the mechanism of action of saxitoxins. The present study showed that activity parameters of aquatic organisms may be a useful tool in the evaluation of sublethal toxicity and detection of neurotoxins in raw water. Environ Toxicol Chem 2014;33:223–229. © 2013 SETAC
Description of the genetic analysis workshop 11 collaborative study on the genetics of alcoholism
Authors: Begleiter H. , Reich T. , Nurnberger J. , Li T.K. , Conneally P.M. , Edenberg H. , Crowe R. , Kuperman S. , Schuckit M. , Bloom F. , Hesselbrock V. , Porjesz B. , Cloninger C.R. , Rice J. , Goate A.
Published: November 2013

Problem 1 of Genetic Analysis Workshop 11 consists of data from a family study of the genetics of alcoholism and related traits contributed by the six centers making up the National Institute for Alcohol Abuse and Alcoholism sponsored by the Collaborative Study on the Genetics of Alcoholism (COGA). The family data included 1,214 members of 105 pedigrees ascertained for having three or more individuals affected with alcoholism. Data available to workshop participants included clinical phenotypes, personality measures, smoking behavior, event‐related potentials, platelet monamine oxidase B activity, and a genome scan of 296 markers.
Brain event‐related potentials, dopamine D2 receptor gene polymorphism, and smoking
Authors: Anokhin A.P. , Todorov A.A. , Madden P.A.F. , Grant J.D. , Heath A.C.
Published: November 2013

This paper explores the relationship between the DRD2 gene polymorphism, P300, and smoking. Both smoking and DRD2 have significant reducing effects on P300 amplitude. The effect of smoking is apparent only in the presence of the A1 allele of the DRD2 locus. Transmission/disequilibrium analyses show a negative association between the A2 allele and smoking initiation, suggesting a protective effect of this allele. When the sample is stratified into lower‐ and higher‐P300 categories, we find a significant association between A1 and current smoking only in individuals with lower P300. Both concordance for smoking and DRD2 genotype are significant predictors of sib‐pair similarity in P300 amplitude. These results suggest a synergistic effect of different neurogenetic risk factors contributing to nicotine dependence. Neurocognitive variation (P300) may moderate the association between DRD2 and smoking. Alternatively, DRD2 genotype may modulate the long‐term impact of nicotine on neurocognitive functioning.
A genome‐wide search for loci contributing to smoking and alcoholism
Authors: Bergen Andrew W. , Korczak Jeannette F. , Weissbecker Karen A. , Goldstein Alisa M.
Published: November 2013

Using the Collaborative Study on the Genetics of Alcoholism (COGA) data, we performed a sib‐pair linkage analysis of two smoking‐related traits and one alcoholism phenotype. The first trait, EVRNVR, was a dichotomous one we constructed based on epidemiological definitions of smoking. The second trait, PKYRS, used the quantitative pack‐year history provided, and the third trait was the COGA alcoholism classification, ALDX1. There was some evidence for linkage of the EVRNVR trait to regions on chromosomes 6, 9, and 14. Smaller numbers of loci provided nominal evidence for linkage to PKYRS, although some candidate gene regions were identified. The number of loci identified using EVRNVR suggests that a threshold‐based phenotype may better identify loci affecting smoking history. Approximately one‐third of the loci that showed evidence for linkage to EVRNVR at a nominal significance level (p < 0.01) also showed evidence for linkage to ALDX1. Some of these regions may represent loci increasing vulnerability to both smoking and alcoholism.
Markov chain monte carlo linkage analysis of a complex qualitative phenotype
Authors: Hinrichs Anthony , Lin Jennifer H. , Reich Theodore , Bierut Laura , Suarez Brian K.
Published: November 2013

We tested a new computer program, LOKI, that implements a reversible jump Markov chain Monte Carlo (MCMC) technique for segregation and linkage analysis. Our objective was to determine whether this software, designed for use with continuously distributed phenotypes, has any efficacy when applied to the discrete disease states of the simulated data from the Mordor data from GAW Problem 1. Although we were able to identify the genomic location for two of the three quantitative trait loci by repeated application of the software, the MCMC sampler experienced significant mixing problems indicating that the method, as currently formulated in LOKI, was not suitable for the discrete phenotypes in this data set.
Genetic dissection of a complex trait
Authors: Lin Jennifer H. , Hinrichs Anthony , Liu Kuang‐Yu , Bierut Laura , Suarez Brian K.
Published: November 2013

A number of genetic and statistical tools were applied to various partitions of the simulated data to identify susceptibility loci, relevant environmental factors, and their interaction(s). The distribution of genotypes at D1G24 among affected children in the first population was found to differ significantly from Hardy‐Weinberg expectation. Two transmission/disequilibrium tests identified the preferential transmission of allele 1 as the source of the disequilibrium. Simple contingency table analysis revealed a positive association between exposure to environmental factor E1 and disease phenotype. Multipoint linkage analyses on various subsets of the data identified three “signal” regions (in addition to the aforementioned D1G24) localized at D1G9–10, D3G45, and D5G38. The even numbered chromosomes appeared to be devoid of susceptibility loci. Further analyses of subsamples of affected sib pairs, selected according to their disease phenotype and their exposure to E1, clarified some linkage relationships, particularly for D3G45, thereby suggesting the presence of a specific gene×environment interaction. Logistic analysis designed to clarify the relationship between disease phenotype and two risk factors (El exposure and the presence of allele 1 at D1G24) in the first population, revealed a significantly negative interaction which, upon learning the details of the generating model, we now attribute to the presence of heterogeneity.
A comparison of some allele‐sharing based linkage analysis methods for detecting complex trait loci
Authors: Liu Ying , Mirea Lucia , Pinnaduwage Dushanthi , Fallah Shafagh , Tritchler David
Published: November 2013

Using randomly selected sib pairs from a subset of the GAW11 simulated data in Problem 2, we compared the results of some linkage analysis methods based on allele sharing. One method was the Haseman‐Elston test for a binary disease outcome (unaffected vs. mild or severe). The other methods, which analyzed the trinary ordered outcome unaffected/mild/severe were the Haseman‐Elston test, an extended Haseman‐Elston incorporating sib‐pair sums, variance components analysis, and regression analysis. Our analysis was done without knowledge of the generating model.
A comparison of two algorithms, multimap and gene mapping system, for automated construction of genetic linkage maps
Authors: Marinov Marin , Matise Tara Cox , Lathrop G. Mark , Weeks Daniel E.
Published: November 2013

Using the GAW11 Problem 2 data set, we compared the performance of two automated map construction algorithms, MultiMap and GMS (Gene Mapping System). The MultiMap algorithm iteratively adds markers in a stepwise manner to the map, while the GMS algorithm seeks to find the best order of the whole set of markers by selective permutations of logically formed subgroups of the markers. While it is difficult to compare these two rather different algorithms, we found that, on these data, GMS performed better than MultiMap, placing more markers in their true order on average, with little order ambiguity. In addition, as the number of markers increased, GMS was less computationally demanding than MultiMap. However, if MultiMap placed a marker, it was almost always in the correct order. In contrast, GMS often placed a group of markers on the wrong end of the map; such incorrect placements occur when the evidence for placement on one end or the other is not strong. Thus, there is room for further algorithmic developments that combine the strengths of both the MultiMap and GMS approaches.
Departure from the triangle constraints in discordant sib pairs: A test for genetic heterogeneity
Authors: Quesneville Hadi , Dizier Marie‐Hélène , Clerget‐Darpoux Françoise
Published: November 2013

For any genetic model, Holmans showed that the proportions of affected sibs sharing 2, 1, or 0 identical‐by‐descent parental marker alleles are constrained to belong to a specific triangle. The triangle constraints do not hold when the sib phenotypes are determined by different models. We test the rejection of triangle constraints on affected sib pairs discordant for severity, to determine whether different models control the severe and mild forms of the disease in the simulated data. With this method we show that a locus on chromosome 5 plays a different role in the two forms of the disease.
Mapping genotype to phenotype for linkage analysis
Authors: Saccone Nancy L. , Downey Thomas J. , Meyer Donald J. , Neuman Rosalind J. , Rice John P.
Published: November 2013

We model functions that use genetic information as input and trait information as output to understand genetic linkage in complex diseases. Using simulated data from GAW11, we have applied categorical classification methods and neural network analysis. We use sharing at selected markers as input, and the classification of the sib pair (for example, affected‐affected or affected‐unaffected) as output. In addition, our methods include environmental risk factors as predictors of phenotype. Categorical and neural network methods each led to results consistent with findings from other methods such as the logistic regression method of Rice et al. [this issue]. Post‐analysis comparison with the GAW11 answers showed that these methods are capable of detecting correct signals in a single replicate. One advantage of our methods is that they allow analysis of the entire genome at once, so that interactions among multiple trait‐influencing loci may be detected. Furthermore, these methods can use a variety of sib pairs rather than affected pairs only.
Systematic search for susceptibility genes in different populations
Authors: Schmidt Silke , Scholz Michael , Loesgen Sabine , Bickeböller Heike
Published: November 2013

We analyzed the first replicate of each of the four simulated population samples from three distinct populations by linkage and association genome scans and could identify three regions with susceptibility loci for the disease: on chromosome 1, marker D1G024, with strong evidence for gene×environment interaction; on chromosome 3, around marker D3G045; and on chromosome 5, markers D5G035–D5G042. Our results were obtained without knowing the true disease model and are compared with this model in the discussion.
Exploring the role of environmental factors in association and linkage studies
Authors: Seillier‐Moiseiwitsch Françoise , Ramaswami Anand , Tripputi Mark , Pankow James , Newman Beth
Published: November 2013

We analyzed some simulated data to assess the success of statistical methodologies to establish the role of the environmental factors (EF) and to identify associated and linked markers. We considered five replicates for each of the four studies, and, with the knowledge of the generating model, concentrated our analyses on chromosomes (CH) 1,3, and 5. To determine the influence of EF and associated markers on the affection status (AS), we utilized chi‐square tests for independence and recursive partitioning (via the CART software). To identify linked markers, we scanned the relevant chromosomes with nonparametric multipoint linkage (NPL) and transmission/disequilibrium tests. These analyses were performed on the whole data set as well as on subsets of individuals and families defined by exposure to EF. CART correctly selected the associated marker (D1G024) and EF1 for Study (ST) 1 and did not generate trees for the other studies. NPL identified the relevant regions on CH3 and CH5 but failed to do so for CH1, except in ST4. Stratifying families by exposure to EF1 did not consistently increase sensitivity of NPL to the relevant CH3 markers, but did help characterize the genetic heterogeneity and identify linked families.
Detecting interactions between gene, site, and environmental variables using GAP
Authors: Shin Janey , Corey Mary
Published: November 2013

Regressive models that incorporate measured variables and assumed genetic parameters were used to detect interactions between gene, research site, and environmental variables in GAW11 Problem 2. Replicates 1 to 5 were used in the analyses. Significant three‐way gene×environment×site interactions were seen for all models, regardless of what assumptions were made about genetic transmission. Therefore, regressive models within each of the four sites were examined for significant gene×environment interactions. At one site, there was a pattern of gene×environment interaction that was consistent in most of the genetic models assumed. Joint and separate segregation and linkage analyses were compared in this site. No patterns of gene×environment interaction were seen in the other sites. Results from this analysis show that regressive modeling can identify complex interactions in data from heterogeneous populations even when ascertainment assumptions are violated.
A bayesian markov chain monte carlo approach to map disease genes in simulated GAW11 data
Authors: Uimari Pekka , Pitkäniemi Janne , Onkamo Päivi
Published: November 2013

A Bayesian method for multipoint mapping of disease genes based on Markov chain Monte Carlo algorithms was applied to the simulated GAW11 data (Study 2). The method is based on repeated Gibbs and more general Metropolis‐Hastings steps. For simplicity we assumed a single disease locus model with two alleles. A normal distribution for the underlying latent variable of the qualitative phenotype was assumed. Based on a single replicate of the data no clear evidence of any of the genes underlying the simulated disease was found. However, when three replicates were combined the method was able to locate the locus C correctly on chromosome 3.
Modeling linkage and association with evaluation of common sampling schemes
Authors: Wicks J. , Wilson S. R.
Published: November 2013

The probability model of parental transmission (of a multiallelic marker) to affected offspring has been reparameterized in such a way as to distinguish the recombination fraction parameter from the association parameters. The advantage of this reparameterization is that statistical tests can be developed which disentangle linkage and association. It is shown that these tests perform well compared with a standard approach that is commonly used. Further, the simulated data (Problem 2) enable a comparison to be made of the performance of these tests under different family sampling schemes.
Using case‐control designs for genome‐wide screening for associations between genetic markers and disease susceptibility loci
Authors: Yang Quanhe , Khoury Muin J. , Atkinson Michael , Sun Fengzhu , Cheng Rong , Flanders W. Dana
Published: November 2013

We used a case‐control design to scan the genome for any associations between genetic markers and disease susceptibility loci using the first two replicates of the Mycenaean population from the GAW11 (Problem 2) data. Using a case‐control approach, we constructed a series of 2‐by‐3 tables for each allele of every marker on all six chromosomes. Odds ratios (ORs) and 95% confidence intervals (95% CI) were estimated for all alleles of every marker. We selected the one allele for which the estimated OR had the minimum p‐value to plot in the graph. Among these selected ORs, we calculated 95% CI for those that had a p‐value ≤ adjusted α level. Significantly high ORs were taken to indicate an association between a marker locus and a suspected disease‐susceptibility gene. For the Mycenaean population, the case‐control design identified allele number 1 of marker 24 on chromosome 1 to be associated with a disease susceptibility gene, OR = 2.10 (95% CI 1.66–2.62). Our approach failed to show any other significant association between case‐control status and genetic markers. Stratified analysis on the environmental risk factor (E1) provided no further evidence of significant association other than allele 1 of marker 24 on chromosome 1. These data indicate the absence of linkage disequilibrium for markers flanking loci A, B, and C.

Finally, we examined the effect of gene×environment (G×E) interaction for the identified allele. Our results provided no evidence of G×E interaction, but suggested that the environmental exposure alone was a risk factor for the disease.
Comparison of GENEHUNTER and MFLINK for analysis of COGA linkage data
Authors: Curtis David , Zhao Jing Hua , Sham Pak C.
Published: November 2013

We compared the NPLALL statistic from GENEHUNTER with two‐point and three‐point MALODs and MFLODs from MFLINK for all autosomal markers in the Collaborative Study on the Genetics of Alcoholism (COGA) data set. In general MFLINK produced more significant results than GENEHUNTER and implicated two regions containing candidate genes (ADH3 and DRD2). Many regions of interest identified in other studies reported at this workshop produced MALODs significant at p ≤ 0.05, but these would not have been picked up by GENEHUNTER unless a less significant threshold were used.
Nonparametric linkage analysis of alcohol dependence with chromosome 1 and 7 markers
Authors: D'Alfonso Sandra
Published: November 2013

We analyzed 105 multiplex families from the Collaborative Study on the Genetics of Alcoholism (COGA) for markers on chromosome 1 (n = 20) and chromosome 7 (n = 19) with the GENEHUNTER program. On chromosome 1, three markers (D1S532, D1S1588, and D1S534) in single‐point analysis and five markers in multipoint analysis (D1S532, D1S1588, D1S1675, D1S534, and D1S1595) showed a nonparametric linkage (NPL) p‐value < 0.05. They mapped in two different but nearby regions, spanning, respectively, 18 cM (D1S532, D1S1588) and 19 cM (D1S1675, D1S534, and D1S1595) and separated by a 20‐cM interval. The highest NPL score was obtained for D1S534 (NPL = 2.26, p = 0.013 for single‐point analysis and NPL = 2.81, p = 0.0029, for multipoint analysis). The maximum NPL score on chromosome 7 was observed for D7S1793 (NPL = 1.72, p = 0.044 for single‐point analysis and NPL = 2.02, p = 0.023 for multipoint analysis). The markers which showed NPL p‐values < 0.05 on chromosome 1 (D1S532, D1S1588, D1S1675, D1S534, and D1S1595) and on chromosome 7 (D7S1793) were analyzed for association using the transmission/disequilibrium test. None of the alleles at these six loci showed a distorted transmission pattern. These data indicate that the two loci “suggestively” linked to alcohol dependence are either in linkage equilibrium with a susceptibility locus or are too far from the susceptibility locus to show disequilibrium, if present.
Smoking behavior is under the influence of a major quantitative trait locus on human chromosome 5q
Authors: Duggirala Ravindranath , Almasy Laura , Blangero John
Published: November 2013

Despite some evidence that smoking behavior is influenced by both genetic and environmental factors, efforts at identifying specific genes that influence smoking are extremely limited. Using information on smoking behavior history for 973 individuals distributed across 105 COGA families and a multipoint variance components method, we tested for linkage between smoking behavior (as defined by number of cigarette packs per day for 1 year) and chromosomal locations across the genome using information from 296 markers. We found strong evidence (lod = 3.2) for linkage of smoking behavior to a genetic location on chromosome 5q (D5S1354). Weaker evidence was found for linkage of smoking behavior to genetic locations on chromosomes 4 (between markers D4S244 and D4S2393), 15 (D15S642), and 17 (GATA193). Oligogenic linkage analyses suggest the putative locus on chromosome 5q is the primary determinant of genetic variation in smoking. Although the magnitude of the lod score is compelling, the large gap between the markers D5S1456 and D5S1354 (which is also at the end of chromosome 5q) in the COGA data set reduces the enthusiasm for this putative quantitative trait locus. However, typing of additional markers in this region may provide greater support for the localization of a susceptibility locus at this chromosomal location, which is not far from the DRD1 (D1 dopamine receptor gene) locus.
The impact of redefining affection status for alcoholism on affected‐sib‐pair analysis
Authors: Fann Cathy S.J. , Shugart Yin Y. , Lachman Herb , Collins Andrew , Chang C.J.
Published: November 2013

The analysis of a complex disease such as alcohol dependence requires a more precise definition of affection status. Collaborative Study on the Genetics of Alcoholism (COGA) provided a variety of qualitative and quantitative measures as well as genotype information, in addition to two criteria of affection status. To identify two groups of phenotypically “more homogeneous” individuals among alcoholics (COGA criterion), we redefined affection status by using cluster analysis and classification and regression tree, incorporating some important covariates such as event related potentials, monoamine oxidase B activity, status of smoking, age of onset, three variables of personality assessed with the Tridimensional Personality Questionnaire and three latent class variables. With redefined affection status, we repeated nonparametric analysis by three sib pair analysis programs (SIBPAL, SIBPAIR, and BETA) using nine candidate DNA markers identified by Reich et al. [1998] and Long et al. [1998]. The goals of our analysis are 1) to confirm previous results for these nine markers with redefined affection status and 2) to compare the performance from these three programs.
Familial analysis of event related potentials
Authors: King Terri M. , Barnholtz Jill , Page Grier P.
Published: November 2013

This report summarizes our analysis of the auditory and visual event related evoked potentials. These data were collected as a component of the Collaborative Study on the Genetics of Alcoholism and distributed as a part of the data available for the Genetic Analysis Workshop 11. For this analysis, we collapsed the data collected from eight leads using principal components methods. Using four collapsed variables derived from the principal components, we used regression analysis to adjust for environmental and demographic variables. We then fit the best fitting regression model and calculated the residuals. Using the residuals, we performed segregation analysis using S.A.G.E. Finally, we applied Markov chain Monte Carlo reverse jump methods to identify areas with potential quantitative trait loci. Our findings indicate that there may be an underlying genetic component to the potentials.
Sib‐pair linkage analyses of alcoholism: Dichotomous and quantitative measures
Authors: Korczak Jeannette F. , Bergen Andrew W. , Goldstein Alisa M. , Weissbecker Karen A.
Published: November 2013

We hypothesized that a quantitative alcoholism trait would have greater power than the Collaborative Study on the Genetics of Alcoholism (COGA) dichotomous alcoholism traits, ALDX1 and ALDX2, to detect putative alcoholism loci. To test this, we performed nonparametric sib‐pair linkage analysis to screen 285 polymorphic autosomal markers for evidence of linkage to ALDX1, ALDX2, and a quantitative trait, QUANT, defined from the 11 COGA latent class variables. We also examined the effects on the analyses of including covariates (sex, age, and pack‐years of smoking) and of transforming QUANT (log and square root). ALDX1 and ALDX2 showed the greatest evidence for linkage to markers on chromosome 1, by both the affected sib‐pair and the Haseman‐Elston tests. Regions of interest were also identified on chromosomes 4, 8, 16, and 17. QUANT showed little evidence for linkage to any chromosomal region, having no more significant results than were expected by chance. Including covariates or transforming QUANT had little effect on the analyses. A quantitative trait based on all 37 latent class variables, with each variable appropriately weighted, may have had more power than QUANT to detect genomic regions of relevance to alcoholism.