bluuebunny/crossref_metadata_2025 huggingface dataset:
ChemInform Abstract: Zahramycins A—B, Two New Steroids from the Coral Sarcophyton trocheliophorum.
Authors: Shaaban Mohamed , Ghani Mohamed A. , Shaaban Khaled A.
Published: November 2013

The two new steroids zahramycins A (I) and B (II) are isolated from the coral Sarcophyton trocheliophorum.
ChemInform Abstract: Cincholenines A and B, Two Unprecedented Quinoline Alkaloids from Cinchona ledgeriana.
Authors: Cheng Gui‐Guang , Zhang Yu , Cai Xiang‐Hai , Bao Mei‐Fen , Gu Ji , Li Yan , Liu Ning , Liu Ya‐Ping , Luo Xiao‐Dong
Published: November 2013

Cincholenines A (Ia) and B (Ib) are evaluated for their cytotoxicity against several human cancer cell lines as well as for their antimalarial potency.
ChemInform Abstract: Casuarines A and B, Lycopodium Alkaloids from Lycopodium casuarinoides.
Authors: Liu Fei , Wu Xing‐De , He Juan , Deng Xu , Peng Li‐Yan , Luo Huai‐Rong , Zhao Qin‐Shi
Published: November 2013

A phytochemical study on Lycopodium casuarinoides leads to the isolation of two new C16N2‐type Lycopodium alkaloids, casuarine A (I), a cage‐like structure featured with a fused 6/6/6/6/6 pentacyclic ring system, and casuarine B (II).
ChemInform Abstract: Search for New Superconductors by Soft‐Chemical Techniques
Authors: Kato Masatsune , Takamatsu Tomohisa , Yagyu Hotaka , Noji Takashi , Koike Yoji
Published: November 2013

Review: 11 refs.
ChemInform Abstract: NMR Crystallography. The Use of Dipolar Interactions in Polymorph and Co‐Crystal Investigation
Authors: Chierotti Michele R. , Gobetto Roberto
Published: November 2013

Review: 99 refs.
ChemInform Abstract: Guanidinyl‐Functionalized Aromatic Compounds (GFAs) — Charge and Spin Density Studies as Starting Points for the Development of a New Class of Redox‐Active Ligands
Authors: Himmel Hans‐Joerg
Published: November 2013

Review: 51 refs.
ChemInform Abstract: Boronic Acid‐Containing Hydrogels: Synthesis and Their Applications
Authors: Guan Ying , Zhang Yongjun
Published: November 2013

Review: 144 refs.
ChemInform Abstract: Chemical Functionalization of Exfoliated Graphene
Authors: Economopoulos Solon P. , Tagmatarchis Nikos
Published: November 2013

Review: 73 refs.
ChemInform Abstract: Conversion of Glucose and Cellulose into Value‐Added Products in Water and Ionic Liquids
Authors: Song Jinliang , Fan Honglei , Ma Jun , Han Buxing
Published: November 2013

Review: more than 150 refs.
ChemInform Abstract: 8‐Aminoquinoline: A Powerful Directing Group in Metal‐Catalyzed Direct Functionalization of C—H Bonds
Authors: Corbet Matthieu , De Campo Floryan
Published: November 2013

Review: 22 refs.
ChemInform Abstract: Palladium‐Catalyzed Chemoselective Catellani ortho‐Arylation Reactions and Their Applications in Natural Products Synthesis
Authors: Sui Xianwei , Zhu Rui , Gu Zhenhua
Published: November 2013

Review: 58 refs.
ChemInform Abstract: Oligoyne Derivatives as Reactive Precursors for the Preparation of Carbon Nanomaterials
Authors: Morin Jean‐Francois
Published: November 2013

Review: 91 refs.
ChemInform Abstract: Unsupported Nanoporous Gold for Heterogeneous Catalysis
Authors: Zhang Xiaomei , Ding Yi
Published: November 2013

Review: 60 refs.
ChemInform Abstract: Recent Advances in Inhibitors of Bacterial Fatty Acid Synthesis Type II (FASII) System Enzymes as Potential Antibacterial Agents
Authors: Wang Yi , Ma Shutao
Published: November 2013

Review: <200 refs.
ChemInform Abstract: A Brief Perspective on the Evolution of Plastic Electronics — From Highly Conducting Polymers to Conjugated Organic Semiconductors
Authors: Skabara Peter J.
Published: November 2013

Review: 30 refs.
ChemInform Abstract: Electrochemical Biosensors on Platforms of Graphene
Authors: Fang Youxing , Wang Erkang
Published: November 2013

Review: 234 refs.
ChemInform Abstract: Some Inherently Chiral Chromophores — Empirical Rules and Quantum Chemical Calculations
Authors: Kwit Marcin , Skowronek Pawel , Gawronski Jacek , Frelek Jadwiga , Woznica Magdalena , Butkiewicz Aleksandra
Published: November 2013

Review: 144 refs.
ChemInform Abstract: Electronic CD of Benzene and Other Aromatic Chromophores for Determination of Absolute Configuration
Authors: Kurtan Tibor , Antus Sandor , Pescitelli Gennaro
Published: November 2013

Review: 152 refs.
ChemInform Abstract: The Determination of the Stoichiometry of Cyclodextrin Inclusion Complexes by Spectral Methods: Possibilities and Limitations
Authors: Tablet Cristina , Matei Iulia , Hillebrand Mihaela
Published: November 2013

Review: 88 refs.
Investigation of Powder Particle Adhesion on Structured Surfaces Using the Vibration Method
Authors: Hartmüller Jürgen , Rudolph Martin , Weiler Rouven , Ripperger Siegfried
Published: November 2013

Die Vibrationsmethode ermöglicht die schnelle und effiziente Ermittlung von Partikelhaftkraftverteilungen zwischen strukturierten Oberflächen und pulverförmigem Schüttgut unter dem Einfluss verschiedener atmosphärischer Bedingungen. In diesem Beitrag werden die Haftkräfte von Fließmittel‐beschichtetem Stärkepulver auf Druckpapier bei verschiedenen relativen Luftfeuchten untersucht und mit Modellen der Partikelhaftung infolge von van‐der‐Waals‐Kräften und von Flüssigkeitsbrücken verglichen.
Tailoring Small Molecules for an Allosteric Site on Procaspase‐6
Authors: Murray Jeremy , Giannetti Anthony M. , Steffek Micah , Gibbons Paul , Hearn Brian R. , Cohen Frederick , Tam Christine , Pozniak Christine , Bravo Brandon , Lewcock Joe , Jaishankar Priyadarshini , Ly Cuong Q. , Zhao Xianrui , Tang Yinyan , Chugha Preeti , Arkin Michelle R. , Flygare John , Renslo Adam R.
Published: November 2013

Although they represent attractive therapeutic targets, caspases have so far proven recalcitrant to the development of drugs targeting the active site. Allosteric modulation of caspase activity is an alternate strategy that potentially avoids the need for anionic and electrophilic functionality present in most active‐site inhibitors. Caspase‐6 has been implicated in neurodegenerative disease, including Huntington’s and Alzheimer’s diseases. Herein we describe a fragment‐based lead discovery effort focused on caspase‐6 in its active and zymogen forms. Fragments were identified for procaspase‐6 using surface plasmon resonance methods and subsequently shown by X‐ray crystallography to bind a putative allosteric site at the dimer interface. A fragment‐merging strategy was employed to produce nanomolar‐affinity ligands that contact residues in the L2 loop at the dimer interface, significantly stabilizing procaspase‐6. Because rearrangement of the L2 loop is required for caspase‐6 activation, our results suggest a strategy for the allosteric control of caspase activation with drug‐like small molecules.
Crystal growth, structure and spectroscopic studies of a novel organic single crystal: L‐lysine p‐nitrophenolate monohydrate (LLNP)
Authors: Wang Lei , Zhang Guanghui , Liu Xitao , Wang Xinqiang , Wang Luning , Zhu Luyi , Xu Dong
Published: November 2013

A novel organic crystal, L‐lysine p‐nitrophenolate monohydrate (LLNP) has been grown successfully from an aqueous solution by the slow cooling method. Transparent single crystal of dimensions 22 × 12 × 12 mm3 has been obtained. The single crystal X‐ray diffraction has shown that LLNP belongs to the orthorhombic crystallographic system with space group P212121. The functional groups and vibrational frequencies of the crystal have been identified using IR and Raman spectra. The proton and carbon configurations have been confirmed through 1H‐NMR and 13C‐NMR spectra analyses. The UV‐Vis‐NIR transmittance spectrum for LLNP crystal has been recorded in the range from 200 to 2500 nm. The second harmonic generation (SHG) intensity of LLNP has been measured by powder SHG method and found to be as 4.2 times as that of KDP. The thermal properties have been studied by using thermo gravimetric (TG) and differential thermal analysis (DTA).
IP‐FCM platform detects the existence and regulator‐caused dissociation of components in naturally assembled HSP90 complex
Authors: Cao Fan‐Fan , Xu Li‐Min , Zhang Xue , Wang Ying , Li Mao‐Quan , Uzan Georges , Peng Bin , Zhang Deng‐Hai
Published: November 2013

Flow cytometry, in conjunction with immunoprecipitation (IP‐FCM), is suggested to have some advantages to conventional IP‐western blot technology in analyzing protein complexes. In this paper, to further examine its practicability, we test the use of IP‐FCM in detecting the HSP90 complex, which has gained importance in drug research and development and involves more than a dozen components. We found that IP‐FCM could effectively detect HSP70, p23, Cdc37, and Cdk6 components in the HSP90 complex naturally formed in U937 cells when this complex was captured by anti‐HSP90 antibody‐coated polystyrene microspheres. IP‐FCM could also detect alteration in components caused by treating cells with HSP90 inhibitors. In a cell‐free environment, IP‐FCM could detect the direct effects of ATP and/or HSP90 inhibitors (17‐N‐allylamino‐17‐demethoxygeldanamycin or celastrol) in causing component dissociation and the time‐ and dose‐effects of inhibitor‐caused dissociation. IP‐FCM is a practical and powerful platform for analyzing HSP90 complex components, and is thus a useful tool in studying HSP90 complex function and screening inhibitors. © 2013 International Society for Advancement of Cytometry
Cochrane in context: Monoclonal antibody for reducing the risk of respiratory syncytial virus infection in children
Authors: Andabaka Tea , Rojas‐Reyes Maria Ximena
Published: November 2013

Cochrane Review: Monoclonal antibody for reducing the risk of respiratory syncytial virus infection in children Andabaka T, Nickerson JW, Rojas‐Reyes MX, Rueda JD, Bacic Vrca V, Barsic B. Monoclonal antibody for reducing the risk of respiratory syncytial virus infection in children. Cochrane Database of Systematic Reviews 2013, Issue 4. Art. No.: CD006602. DOI: 10.1002/14651858.CD006602.pub4

This companion piece to the review, “Monoclonal antibody for reducing the risk of respiratory syncytial virus infection 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 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
Corticosteroids for the prevention of bronchopulmonary dysplasia in preterm infants: an overview of Cochrane reviews
Authors: Harrold J. , Ali S. , Oleszczuk M. , Lacaze‐Masmonteil T. , Hartling L.
Published: November 2013

Background

Bronchopulmonary dysplasia (BPD) is an important complication associated with considerable morbidity in preterm infants. Corticosteroids in various regimens have been tried out to prevent BPD.

Objective

To examine the evidence from Cochrane systematic reviews regarding the effectiveness and associated complications of corticosteroids used to prevent BPD in preterm infants.

Methods

The Cochrane Database of Systematic Reviews was searched to identify reviews of corticosteroids for BPD in preterm infants. Data were extracted by one investigator, and checked by a second investigator for accuracy. Results are presented as risk ratios (RR) with 95% confidence intervals (CI). We considered <8 days as early and >7 days as late administration.

Main results

Six reviews (67 trials and 6535 patients) were included and covered three main comparisons: inhaled corticosteroids versus placebo, inhaled versus systemic corticosteroids and systemic corticosteroids versus placebo. Systemic corticosteroids compared with placebo significantly reduced the incidence of BPD (early: RR 0.79, 95% CI 0.71–0.88; late: RR 0.72, 95% CI 0.63–0.82), and BPD or mortality (early: RR 0.89, 95% CI 0.84–0.95; late: RR 0.72, 95% CI 0.63–0.82) at 36 weeks post‐menstrual age. Similar results were observed for these outcomes assessed at 28 days of life at which time there was additionally a reduction in mortality (late: RR 0.49, 95% CI 0.28–0.85). There was a higher incidence of cerebral palsy associated with systemic corticosteroids compared with placebo when initiated early (RR 1.45, 95% CI 1.06–1.98). No differences in neurodisability based on Bayley Mental or Psychomotor Developmental Index scores were observed for inhaled or systemic corticosteroids compared with placebo. Hypertension was significantly increased in association with systemic corticosteroids versus placebo (early: RR 1.85, 95% CI 1.55–2.22; late: RR 2.66, 95% CI 1.58–4.49) as were gastrointestinal (GI) perforations when treatment was initiated early (RR 1.81, 95% CI 1.33–2.48).

Author's Conclusion

Systemic corticosteroids decrease BPD and early mortality in premature infants but have a risk of complications, particularly when initiated in the first week of life. Owing to the wide range of dosing protocols, timing of initiation, doses and duration of therapy in the included reviews, it is difficult to determine, based on the evidence examined in this overview, a protocol that is both safe and effective. Further research should focus on determining the most effective dose and timing of corticosteroid administration beyond the first week of life to maximize benefit in decreasing BPD and mortality while avoiding short‐ and long‐term harms.
Push‐Pull Design of Bis(tridentate) Ruthenium(II) Polypyridine Chromophores as Deep Red Light Emitters in Light‐Emitting Electrochemical Cells
Authors: Breivogel Aaron , Park Myeongjin , Lee Donggu , Klassen Stefanie , Kühnle Angelika , Lee Changhee , Char Kookheon , Heinze Katja
Published: November 2013

Light‐emitting electrochemical cells (LECs) with a simple device structure were prepared by using heteroleptic bis(tridentate) ruthenium(II) complexes [1](PF6)2–[3](PF6)2 as emitters. The push‐pull substitution shifts the emission energy to low energy, into the NIR region. The devices emit deep red light up to a maximum emission wavelength of 755 nm [CIE (International Commission on Illumination) coordinates: x = 0.731, y = 0.269 for [3](PF6)2], which, to the best of our knowledge, is the lowest emission energy for LECs containing bis(tridentate) ruthenium(II) complexes. A device structure of ITO/PEDOT:PSS/ruthenium(II) complex/Ag was used, and the thickness of the emitting layer was measured by AFM [ITO: indium tin oxide, PEDOT: poly(3,4‐ethylenedioxythiophene), PSS: poly(styrenesulfonate), AFM: atomic force microscopy]. To enhance the external quantum efficiency (EQE), cells were fabricated with and without poly(methyl methacrylate) (PMMA) as additive in the emitting layer.
Ring‐Opening/Ring‐Closing Protocols from Nitrothiophenes: Easy Access to N‐Fused Pyrroles through a Tandem 1,6‐H Shift/6π‐Electrocyclization
Authors: Bianchi Lara , Maccagno Massimo , Petrillo Giovanni , Scapolla Carlo , Tavani Cinzia , Tirocco Alessandra
Published: November 2013

The ring opening of 3‐nitro‐4‐(phenylsulfonyl)thiophene with amines and proper modification of the resulting 1,3‐diene enables a simple and versatile approach to N‐fused pyrroles of both synthetic and biological interest through 1,6‐H shift followed by 6π 1,5‐electrocyclization. This protocol is effectively driven to the isolated pyrroles by an easy aromatization.
Determination of column size for displacement‐based design of reinforced concrete frame buildings
Authors: Mayengbam S. S. , Choudhury S.
Published: November 2013

This article reports a method to determine the storey‐wise column size for displacement‐based design of reinforced concrete frame buildings with a wide range of storey drift and building plan. The method uses a computer program based algorithm. The basic relation used in the algorithm is formulated by considering the various possible deformation components involved in the overall frame deformation. As a necessity to represent the deformation component due to plastic rotation of beam members, a relation between the beam plastic rotation and the target‐drift is adopted. To control the dynamic amplification of interstorey drift, a target‐drift dependant design‐drift reduction factor is used. The dynamic amplification of column moment is accounted with the help of an approximate conversion of fundamental period of the building from the effective period of the equivalent SDOF system. To avoid the formation of plastic hinge in column members, a design‐drift dependant column–beam moment capacity ratio is used. The method successfully determines the storey‐wise column size for buildings of four plans of different varieties, heights up to 12 storeys and target‐drift up to 3%. Copyright © 2013 John Wiley & Sons, Ltd.
A method for meta‐analysis of genome searches: Application to simulated data
Authors: Wise Lesley H. , Lewis Cathryn M.
Published: November 2013

Genome searches have been performed for many complex traits, and in some cases several searches have been performed in a single disease. Replication of significant results is rare, and a systematic method of reviewing results from a number of searches is needed. A method for meta‐analysis is presented which provides a systematic descriptive overview of the separate analyses while dealing with some of the problems specific to meta‐analysis of genome searches. The results of two separate meta‐analyses correctly indicate the presence of susceptibility loci on chromosomes 1, 3, and 5 in the GAW11 Problem 2 data.
Evaluation of replication studies, combined data analysis, and analytical methods in complex diseases
Authors: Xu Jianfeng , Wiesch Denise G. , Taylor Eugene W. , Meyers Deborah A.
Published: November 2013

Due to genetic heterogeneity, phenocopies, incomplete penetrance, misdiagnosis, and unknown mode of inheritance, linkage studies of most complex diseases are unlikely to provide conclusive findings with unambiguously high lod scores. Typically, several marginally significant lod scores or elevated lod scores are observed in a genome‐wide screen. However, it is usually difficult to differentiate these findings from false positives (type I errors). Two approaches are commonly used to guard against false positives: replication studies in independent samples and combined data analysis. In the current paper, we evaluated these two common approaches using simulated data where data from multiple groups were available and locations of disease genes were known. We found replication studies and combined data analysis performed similarly in terms of their ability to identify true and false positive linkages. Both approaches confirmed two true linkages and did not confirm any false positive linkages. The results also indicated that it is not appropriate to apply the criteria proposed for confirming significant evidence for linkage to confirm regions with only suggestive evidence for linkage. The current results support previous findings that parametric analysis using an incorrect genetic model can still identify a true linkage.
Comparison of empirical strategies to maximize GENEHUNTER lod scores
Authors: Chen Chien H. , Finch Stephen J. , Mendell Nancy R. , Gordon Derek
Published: November 2013

We compare four strategies for finding the settings of genetic parameters that maximize the lod scores reported in GENEHUNTER 1.2. The four strategies are iterated complete factorial designs, iterated orthogonal Latin hypercubes, evolutionary operation, and numerical optimization. The genetic parameters that are set are the phenocopy rate, penetrance, and disease allele frequency; both recessive and dominant models are considered. We selected the optimization of a recessive model on the Collaborative Study on the Genetics of Alcoholism (COGA) data of chromosome 1 for complete analysis. Convergence to a setting producing a local maximum required the evaluation of over 100 settings (for a time budget of 800 minutes on a Pentium II 300 MHz PC). Two notable local maxima were detected, suggesting the need for a more extensive search before claiming that a global maximum had been found. The orthogonal Latin hypercube design was the best strategy for finding areas that produced high lod scores with small numbers of evaluations. Numerical optimization starting from a region producing high lod scores was the strategy that found the highest maximum observed.
Monte carlo markov chain methods for genome screening
Authors: Daw E.W. , Kumm J. , Snow G.L. , Thompson E.A. , Wijsman E.M.
Published: November 2013

We used Monte Carlo Markov chain (MCMC) methods to analyze a quantitative trait, MAO level, and a discrete trait, Collaborative Study on the Genetics of Alcoholism (COGA) alcoholism. Segregation, linkage, and haplotype sharing were analyzed and effects of marker map features were examined. For MAO, modest signals were found on chromosomes 1 and 17 for raw data, and 15 for covariate‐adjusted data. For alcoholism, a strong signal was found on chromosome 1 with modest signals on chromosomes 4 and 10.
Comparison of two linkage inference procedures for genes related to the P300 component of the event related potential
Authors: Goldin Lynn R. , Chase Gary A.
Published: November 2013

Our goal was to detect genes contributing to the P300 component of the event related potential (ERP). We found that all of the ERP traits were highly correlated. Most of them distinguished alcoholics from nonalcoholics. To have one summary variable for the ERP traits, we calculated the first principal component (PRIN1). After adjusting for age and sex, we screened for linkage of PRIN1 to all of the markers using the two‐point Haseman‐Elston sib‐pair test. We compared results obtained from computing a moving average of two‐point p‐values (“regional” inference) in an approximately 10 cM region with those obtained from single, two‐point tests. Different “suggestive” and “significant” linkage regions were found using the two methods. Based on the regional method, areas on chromosomes 2 and 5 should be followed up in future studies.
An empirical test of the significance of an observed quantitative trait locus effect that preserves additive genetic variation
Authors: Iturria Stephen J. , Williams Jeff T. , Almasy Laura , Dyer Thomas D. , Blangero John
Published: November 2013

We propose a constrained permutation test that assesses the significance of an observed quantitative trait locus effect against a background of genetic and environmental variation. Permutations of phenotypes are not selected at random, but rather are chosen in a manner that attempts to maintain the additive genetic variability in phenotypes. Such a constraint maintains the nonindependence among observations under the null hypothesis of no linkage. The empirical distribution of the lod scores calculated using permuted phenotypes is compared to that obtained using phenotypes simulated from the assumed underlying multivariate normal model. We make comparisons of univariate analyses for both a quantitative phenotype that appears consistent with a multivariate normal model and a quantitative phenotype containing pronounced outliers. An example of a bivariate analysis is also presented.
Sib‐pair analysis of the collaborative study on the genetics of alcoholism data set
Authors: Jorgenson Eric , Hinds David , Risch Neil
Published: November 2013

Nonparametric sib‐pair analysis was performed on the Collaborative Study on the Genetics of Alcoholism data set. Concordant and discordant pair groups were examined using the ASPEX package of programs. Allele sharing and multipoint lod scores for six comparison groups were obtained. Sharing and lod score patterns were not consistent with a simple genetic interpretation.
Searching for alcoholism susceptibility genes using markov chain monte carlo methods
Authors: Leal Suzanne M. , Heath Simon C.
Published: November 2013

Markov chain Monte Carlo (MCMC) methods offer a rapid parametric approach that can test for linkage throughout the entire genome. It has an advantage similar to nonparametric methods in that the model does not have to be completely specified a priori. However, unlike nonparametric methods, there are no limitations on pedigree size and MCMC methods can also handle relatively complex pedigree structures. In addition MCMC methods can be used to carry segregation analysis in order to answer questions on the genetic components of a disease phenotype. Segregation analysis gave evidence for between two and eight alcoholism susceptibility loci, each having a modest effect on the phenotype. MCMC methods were used to map alcoholism loci using the phenotypes ALDX1 (DSM‐III‐R and Feighner criteria) and ALDX2 (World Health Organization diagnosis ICD‐10 criteria). There was mild evidence for quantitative trait loci on chromosomes 2,10, and 11.
Identifying influential individuals in linkage analysis: Application to a quantitative trait locus detected in the COGA data
Authors: Mitchell Braxton D. , Ghosh Soumitra , Watanabe Richard M. , Slifer Susan H. , Hsueh Wen‐Chi , Birznieks Gunther
Published: November 2013

Once linkage is detected to a quantitative trait locus (QTL), the next step towards localizing the gene involved may be to identify those families, or individuals, in whom the putative mutations are segregating. In this paper, we describe a jackknife procedure for identifying individuals (and families) who contribute disproportionately to the linkage. Following initial detection of linkage to a QTL, the strategy involves sequentially removing each individual (or each family) from the analysis and recomputing the lod score associated with the linked region using data from all remaining subjects (or families). This procedure can be used to determine if particular observations have substantial impact on evidence for linkage. Identification of such observations may provide insights for further efforts to localize the QTL.
Structural decomposition of genetic diversity in families with alcoholism
Authors: Stassen Hans H. , Begleiter Henri , Porjesz Bernice , Rice John , Scharfetter Christian , Reich Theodore
Published: November 2013

Using genotypes of 280 marker loci on the 22 autosomes of 105 alcohol‐dependent probands, their affected and unaffected sibs, as well as their parents, we iteratively constructed a genetic similarity function that enabled us to quantify the interindividual genetic distances d(xixj) between feature vectors xi,xjmade up by the allelic patterns of individuals i, j with respect to loci 11 12, …, 1n. Based on this similarity function, we investigated the sib‐sib similarities that are expected to deviate from “0.5” in affected sib pairs if the region of interest contains markers close to disease‐causing genes. The reference value “0.5” was derived from the parents‐offspring similarities, because these are independent of the affection status. The question of population admixture was addressed by means of multivariate structural analyses. These analyses led to four “natural” groups whose validity was tested through the father‐mother similarities. Additionally, we determined the eigenvectors that optimally represented the genetic variation and found several marker configurations on chromosomes 1, 3, 7, 15, and 17 that reproducibly discriminated (p ≤ 0.01) affected probands/sibs from unaffected sibs, while no such differences were found between affected probands and affected sibs.
Whole genome association studies for genes affecting alcohol dependence
Authors: Sun Fengzhu , Cheng Rong , Flanders W. Dana , Yang Quanhe , Khoury Muin J.
Published: November 2013

We applied the transmission/disequilibrium test (TDT) for sibs (S‐TDT) and for families with one parent (1‐TDT), to the Collaborative Study on the Genetics of Alcoholism data set. The combined test is used to screen the whole genome to locate genes responsible for alcohol dependence. This analysis supports the previous finding that the region close to GABRB1 on chromosome 4 might be associated with alcohol dependence. The regions close to D6S474 and D11S1998 are also of particular interest. We found segregation distortion at the GR1K1 locus. The segregation distortion might be due to the binning method used in genotyping at this locus.
Application of an ordered subset analysis approach to the genetics of alcoholism
Authors: Watanabe Richard M. , Ghosh Soumitra , Birznieks Gunther , Duren William L. , Mitchell Braxton D.
Published: November 2013

For complex diseases, underlying etiologic heterogeneity may reduce power to detect linkage. Thus, methods to identify more homogeneous subgroups within a given sample in a linkage study may improve detection of putative susceptibility loci. In this study we describe an ordered subsetting approach that utilizes disease‐related quantitative trait data to complement traditional linkage analysis. This approach uses family‐based lod scores derived from the initial genome screen and a family‐based descriptor of the trait of interest. The goal of the approach is to identify more homogeneous subgroups of the data by ranking families based on their quantitative trait data. Permutation testing is used to assess statistical significance. This approach can be adapted to a variety of linkage methods and may provide a means to dissect some of the underlying heterogeneity in complex disease genetics.
Parental sex effect in families with alcoholism
Authors: Wyszynski Diego F. , Panhuysen Carolien I. M.
Published: November 2013

Parental sex effects have been shown to influence the inheritance of a number of complex disorders. In this paper we performed affected sib‐pair analyses on 105 families with recurrent alcoholism to evaluate the effects that the parent of origin might have on this disorder. Three alternative classification schemes were used and the families were grouped as maternal, paternal, mixed, or unknown. Paternal effects were observed at D9S64, D16S475, and D16S2622, while maternal effects were expressed at FABP2, D8S280, D8S1715, and D8S1988. Except for D16S2622, none of these markers resulted in a significant p‐value when all families were analyzed together. These results suggest that the parental sex should not be ignored and that a discriminatory analysis should always be performed.
Summary of analyses of problem 2 simulated data for GAW11
Authors: Greenberg D.A.
Published: November 2013

The simulated data for Problem 2 of the 11th Genetic Analysis Workshop (GAW11) consisted of family linkage data and disease data from three populations, each population with different genetic parameters. The disease was simulated such that there were two genetically distinct diseases, one caused by a single locus with three alleles and the other by two epistatically interacting loci. The two diseases were clinically identical. Each of the diseases had a severe and mild form. One of the diseases was influenced by an environmental factor and one by an allele at one of the marker loci (association). Linkage data consisted of 300 polymorphic markers. Investigators analyzed these data in a myriad of ways, using most currently available linkage techniques and association analysis methods. In addition, investigators also tested newly developed methods, some of which took advantage of the existence of the environmental component. Other types of analyses included meta‐analyses, methods of combining data from different studies, questions of replication, how much information is available in a single data set, and analyses for gene×gene and gene×environment interaction.
Genetic analysis of a complex disease in the presence of an environmental risk factor
Authors: Eichenbaum‐Voline Sophie , Baur Max P. , Knapp Michael
Published: November 2013

The role of a gene in a disease may be hidden by the presence of another risk factor such as an environmental factor. In that case, stratifying the data according to this factor strengthens power to detect linkage or association. We followed this strategy on the simulated data provided by GAW11. The transmission/disequilibrium test (TDT) and the maximum likelihood score (MLS) were performed on the first replicate of 100 sib pairs from the population in which the disease risk was significantly influenced by an environmental factor (E1). However, only the TDT was powerful enough to detect one of the four loci involved in the genetic determination of the disease. The MLS showed no evidence for linkage after taking into account the fact that multiple tests were performed. Even when stratifying the sample according to the presence of E1, no additional loci could be detected. Given the simulated models, 100 sib pairs are too low a sample size for a systematic screening of the genome, which in this case was an analysis of 300 markers.
Meta‐analysis by combining parameter estimates: Simulated linkage studies
Authors: Goldstein Darlene R. , Sain Stephan R. , Guerra Rudy , Etzel Carol J.
Published: November 2013

Several meta‐analytic techniques have been developed for combining information from multiple studies in contexts other than linkage detection. We apply the technique of combining parameter estimates to the problem of finding disease loci in the simulated data and compare results with those obtained by reanalyzing pooled raw data. To facilitate the combination of study results, we highly recommend that parameter estimates and their standard errors be reported in published studies. If different research groups were to make original data available, progress toward disease gene location and characterization may be more quickly made.
Liver-primed CD8+ T cells suppress antiviral adaptive immunity through galectin-9-independent T-Cell immunoglobulin and mucin 3 engagement of high-mobility group box 1 in mice
Authors: Dolina Joseph S. , Braciale Thomas J. , Hahn Young S.
Published: November 2013

The liver is a tolerogenic environment exploited by persistent infections, such as hepatitis B (HBV) and C (HCV) viruses. In a murine model of intravenous hepatotropic adenovirus infection, liver-primed antiviral CD8+ T cells fail to produce proinflammatory cytokines and do not display cytolytic activity characteristic of effector CD8+ T cells generated by infection at an extrahepatic, that is, subcutaneous, site. Importantly, liver-generated CD8+ T cells also appear to have a T-regulatory (Treg) cell function exemplified by their ability to limit proliferation of antigen-specific T-effector (Teff) cells in vitro and in vivo via T-cell immunoglobulin and mucin 3 (Tim-3) expressed by the CD8+ Treg cells. Regulatory activity did not require recognition of the canonical Tim-3 ligand, galectin-9, but was dependent on CD8+ Treg cell-surface Tim-3 binding to the alarmin, high-mobility group box 1 (HMGB-1). Conclusion: Virus-specific Tim-3+CD8+ T cells operating through HMGB-1 recognition in the setting of acute and chronic viral infections of the liver may act to dampen hepatic T-cell responses in the liver microenvironment and, as a consequence, limit immune-mediated tissue injury or promote the establishment of persistent infections. (HEPATOLOGY 2014;59:1351-1365)
KRAS mutations and CDKN2A promoter methylation show an interactive adverse effect on survival and predict recurrence of rectal cancer
Authors: Kohonen‐Corish Maija R. J. , Tseung Jason , Chan Charles , Currey Nicola , Dent Owen F. , Clarke Stephen , Bokey Les , Chapuis Pierre H.
Published: November 2013

Colonic and rectal cancers differ in their clinicopathologic features and treatment strategies. Molecular markers such as gene methylation, microsatellite instability and KRAS mutations, are becoming increasingly important in guiding treatment decisions in colorectal cancer. However, their association with clinicopathologic variables and utility in the management of rectal cancer is still poorly understood. We analyzed CDKN2A gene methylation, CpG island methylator phenotype (CIMP), microsatellite instability and KRAS/BRAF mutations in a cohort of 381 rectal cancers with extensive clinical follow‐up data. BRAF mutations (2%), CIMP‐high (4%) and microsatellite instability‐high (2%) were rare, whereas KRAS mutations (39%), CDKN2A methylation (20%) and CIMP‐low (25%) were more common. Only CDKN2A methylation and KRAS mutations showed an association with poor overall survival but these did not remain significant when analyzed with other clinicopathologic factors. In contrast, this prognostic effect was strengthened by the joint presence of CDKN2A methylation and KRAS mutations, which independently predicted recurrence of cancer and was associated with poor overall and cancer‐specific survival. This study has identified a subgroup of more aggressive rectal cancers that may arise through the KRAS‐p16 pathway. It has been previously shown that an interaction of p16 deficiency and oncogenic KRAS promotes carcinogenesis in the mouse and is characterized by loss of oncogene‐induced senescence. These findings may provide avenues for the discovery of new treatments in rectal cancer.
A CagA‐independent cluster of antigens related to the risk of noncardia gastric cancer: Associations between Helicobacter pylori antibodies and gastric adenocarcinoma explored by multiplex serology
Authors: Song Huan , Michel Angelika , Nyrén Olof , Ekström Anna‐Mia , Pawlita Michael , Ye Weimin
Published: November 2013

Because of the differences in bacterial epitopes and host characteristics, infections with Helicobacter pylori (H. pylori) induce different immune responses. We explored the possibility that certain antibody response patterns are more closely linked to gastric adenocarcinoma (GAC) than others. In a Swedish population‐based case‐control study, serum samples were obtained from 268 cases and 222 controls, aged 40–79 years and frequency‐matched according to age and sex. We measured antibodies against 17 H. pylori proteins using multiplex serology. Associations were estimated with multivariably adjusted logistic regression models, using odds ratio (OR) with 95% confidence interval (CI) as measures of relative risk. Associations were essentially confined to non‐cardia GAC but did not differ significantly between intestinal and diffuse subtypes. Point estimates for all antibodies were above unity, 15 significant with top three being CagA (OR = 9.2), GroEL (6.6), HyuA (3.6). ORs were substantially attenuated in individuals with chronic atrophic gastritis. Principal component analysis identified two significant factors: a CagA‐dominant factor (antibodies against CagA, VacA and Omp as prominent markers), and a non‐CagA factor (antibodies against NapA and Catalase as prominent markers). Both factors showed dose‐dependent associations with non‐cardia GAC risk (CagA‐dominant factor, highest vs. lowest quartiles, OR = 16.2 [95% CI 4.8–54.9]; non‐CagA factor OR = 5.3 [95% CI 2.1–13.3]). Overall, our results confirm that serum antibodies against different H. pylori proteins are associated with the presence of non‐cardia GAC. Although strongest association is detected by antibodies against CagA and covarying proteins, a pattern of antibodies unrelated to CagA is also significantly linked to the risk of non‐cardia GAC.
Subpopulations of myeloid‐derived suppressor cells impair T cell responses through independent nitric oxide‐related pathways
Authors: Raber Patrick L. , Thevenot Paul , Sierra Rosa , Wyczechowska Dorota , Halle Daniel , Ramirez Maria E. , Ochoa Augusto C. , Fletcher Matthew , Velasco Cruz , Wilk Anna , Reiss Krzysztof , Rodriguez Paulo C.
Published: November 2013

The accumulation of myeloid‐derived suppressor cells (MDSC) in tumor‐bearing hosts is a hallmark of malignancy‐associated inflammation and a major mediator for the induction of T cell suppression in cancer. MDSC can be divided phenotypically into granulocytic (G‐MDSC) and monocytic (Mo‐MDSC) subgroups. Several mechanisms mediate the induction of T cell anergy by MDSC; however, the specific role of these pathways in the inhibitory activity of MDSC subpopulations remains unclear. Therefore, we aimed to determine the effector mechanisms by which subsets of tumor‐infiltrating MDSC block T cell function. We found that G‐MDSC had a higher ability to impair proliferation and expression of effector molecules in activated T cells, as compared to Mo‐MDSC. Interestingly, both MDSC subgroups inhibited T cells through nitric oxide (NO)‐related pathways, but expressed different effector inhibitory mechanisms. Specifically, G‐MDSC impaired T cells through the production of peroxynitrites (PNT), while Mo‐MDSC suppressed by the release of NO. The production of PNT in G‐MDSC depended on the expression of gp91phox and endothelial NO synthase (eNOS), while inducible NO synthase (iNOS) mediated the generation of NO in Mo‐MDSC. Deletion of eNOS and gp91phox or scavenging of PNT blocked the suppressive function of G‐MDSC and induced anti‐tumoral effects, without altering Mo‐MDSC inhibitory activity. Furthermore, NO‐scavenging or iNOS knockdown prevented Mo‐MDSC function, but did not affect PNT production or suppression by G‐MDSC. These results suggest that MDSC subpopulations utilize independent effector mechanisms to regulate T cell function. Inhibition of these pathways is expected to specifically block MDSC subsets and overcome immune suppression in cancer.
Socioeconomic deprivation and cancer survival in Germany: An ecological analysis in 200 districts in Germany
Authors: Jansen Lina , Eberle Andrea , Emrich Katharina , Gondos Adam , Holleczek Bernd , Kajüter Hiltraud , Maier Werner , Nennecke Alice , Pritzkuleit Ron , Brenner Hermann ,   for the GEKID Cancer Survival Working Group
Published: November 2013

Although socioeconomic inequalities in cancer survival have been demonstrated both within and between countries, evidence on the variation of the inequalities over time past diagnosis is sparse. Furthermore, no comprehensive analysis of socioeconomic differences in cancer survival in Germany has been conducted. Therefore, we analyzed variations in cancer survival for patients diagnosed with one of the 25 most common cancer sites in 1997–2006 in ten population‐based cancer registries in Germany (covering 32 million inhabitants). Patients were assigned a socioeconomic status according to the district of residence at diagnosis. Period analysis was used to derive 3‐month, 5‐year and conditional 1‐year and 5‐year age‐standardized relative survival for 2002–2006 for each deprivation quintile in Germany. Relative survival of patients living in the most deprived district was compared to survival of patients living in all other districts by model‐based period analysis. For 21 of 25 cancer sites, 5‐year relative survival was lower in the most deprived districts than in all other districts combined. The median relative excess risk of death over the 25 cancer sites decreased from 1.24 in the first 3 months to 1.16 in the following 9 months to 1.08 in the following 4 years. Inequalities persisted after adjustment for stage. These major regional socioeconomic inequalities indicate a potential for improving cancer care and survival in Germany. Studies on individual‐level patient data with access to treatment information should be conducted to examine the reasons for these socioeconomic inequalities in cancer survival in more detail.
Liquid Junction Potentials and Transference Numbers in Montmorillonite Suspensions
Authors: Shainberg I. , Caiserman A.
Published: November 2013

The EMF's of concentration cells with and without transference were determined. The cells consist of two compartments each containing an equal concentration of K‐montmorillonite with a different KCl concentration at the two sides of the liquid junction. The EMF's were determined with Ag/AgCl electrodes and a K‐sensitive glass electrode. The liquid junction potential and the transference number of the ionic species in the suspensions were calculated from the data of the EMF. The liquid junction potential (being zero for KCl solution), and the transference number of K+, were found to increase with the increase in the clay concentration. This indicates that pH measurements in clay suspensions involve a liquid junction at the KCl bridge which cannot be disregarded.
Electron Microscopic and Kinetic Study of the Flocculation of Calcium Montmorillonite
Authors: Fitzsimmons R. F. , Posner A. M. , Quirk J. P.
Published: November 2013

Electron microscope studies have shown that calcium montmorillonite, originally dispersed into separate platelets, flocculates with time to form large flat sheet‐like particles which exhibit pronounced flow birefringence. Although kinetic studies indicate for rapid salt flocculation face to face condensation is unlikely to occur, it has been shown that with long times in electrolyte free systems a small amount of perpendicular stacking occurs, resulting in the development of particles four layers thick. During the same period the sodium montmorillonite suspension remains unchanged. Lateral growth of the particles is most likely brought about by an intermediate orientation of the particles with overlapping of the edges of the particles, so that they link together to form a flat sheet. These results prove that in suspension calcium montmorillonite quasi crystals definitely have different dimensions from the original sodium montmorillonite. Kinetic and electron microscope studies of salt flocculated calcium montmorillonite systems indicate that the salt floccules consist of particles randomly oriented relative to one another. However electron microscope studies show that salt floccules may undergo rearrangements, depending on their treatment, resulting in a greater ordering of individual particles. Dialysis of the salt flocculated system leads to birefringent units similar to those formed in the absence of salt. Further stacking and lateral growth is induced by drying. These results explain the very different surface areas of calcium montmorillonite determined by chloride exclusion measurements.
Anilinium Montmorillonites and the Formation of Ammonium/Amine Associations
Authors: Heller Lisa , Yariv S.
Published: November 2013

The IR spectra, X‐ray patterns and DTA curves of various aryl ammonium montmorillonites, are characterized. Depending upon the particular amine, the aryl ammonium ions react with excess base by (1) showing a proton equally between two amine molecules through a water bridge, (2) by retaining the proton identified with one molecule, or (3) by polymerization liberating protons. It is inferred that interlayer alkyl ammonium ions also show protons with excess amine through water bridges but the stability of the aryl and alkyl compounds differs greatly.
Non‐Exchangeable Ammonium Ions in Some Clays and Shales of Israel
Authors: Yaalon D.H. , Feigin A.
Published: November 2013

Inorganic lattice‐bound ammonium was determined in a representative assemblage of Israeli shales and clayey rocks. Clays in which illite was the dominant mineral contained over 300 ppmN or >2 meq NH4/100g clay. This represents some 75% of the total nitrogen of the samples. Montmorillonite rich clays in marine sediments with small amounts of illite contained 0.5–1.5 meq NH4/100g clay or about 60% of the total N in the inorganic form. Montmorillonitic red beds held only small amounts of inorganically bound ammonium and kaolinitic clays, both of residual weathering and of hydrothermal origin, contained practically none.
Molecular Structure of the New Copper Complexes. VIII. Infrared Spectroscopic Evidence of the Cu2+ Ion Interaction with Aniline Derivates (Chloro and Nitroanilines)
Authors: Crâciunescu D. , Oancea D.
Published: November 2013

Copper (II) complexes of the types [CuCl2L2] and [CuCl4]H2·2L, where L = m and p nitroaniline, (o, m and p) chloroaniline were prepared in solid crystalline form and their IR spectra was recorded at 25°C as Nujoll mulls and KBr pellets. A close linear relationship between the strength of the Cu ‐ N bond, deduced from the perturbations of the NH2 stretching frequencies, and the basic strength of the amino group were observed.