bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fine‐mapping reveals novel alternative splicing of the dopamine transporter
Authors: Talkowski Michael E. , McCann Kathleen L. , Chen Michael , McClain Lora , Bamne Mikhil , Wood Joel , Chowdari Kodavali V. , Watson Annie , Prasad Konasale M. , Kirov George , Georgieva Lyudmilla , Toncheva Draga , Mansour Hader , Lewis David A. , Owen Michael , O'Donovan Michael , Papasaikas Panagiotis , Sullivan Patrick , Ruderfer Douglas , Yao Jeffrey K , Leonard Sherry , Thomas Pramod , Miyajima Fabio , Quinn John , Lopez A. Javier , Nimgaonkar Vishwajit L. 
Published: October 2010

AbstractThe dopamine transporter gene (SLC6A3,DAT) has been implicated in the pathogenesis of numerous psychiatric and neurodevelopmental disorders, including schizophrenia (SZ). We previously detected association between SZ and intronicSLC6A3variants that replicated in two independent Caucasian samples, but had no obvious function. In follow‐up analyses, we sequenced the coding and intronic regions ofSLC6A3to identify complete linkage disequilibrium patterns of common variations. We genotyped 78 polymorphisms, narrowing the potentially causal region to two correlated clusters of associated SNPs localized predominantly to introns 3 and 4. Our computational analysis of these intronic regions predicted a novel cassette exon within intron 3, designated E3b, which is conserved among primates. We confirmed alternative splicing of E3b in post‐mortem human substantia nigra (SN). As E3b introduces multiple in‐frame stop codons, theSLC6A3open reading frame is truncated and the spliced product may undergo nonsense mediated decay. Thus, factors that increase E3b splicing could reduce the amount of unspliced product available for translation. Observations consistent with this prediction were made using cellular assays and in post‐mortem human SN. In mini‐gene constructs, the extent of splicing is also influenced by at least two common haplotypes, so the alternative splicing was evaluated in relation to SZ risk. Meta‐analyses across genome‐wide association studies did not support the initial associations and further post‐mortem studies did not suggest case‐control differences in splicing. These studies do not provide a compelling link to schizophrenia. However, the impact of the alternative splicing on other neuropsychiatric disorders should be investigated. © 2010 Wiley‐Liss, Inc.
Childhood maltreatment, the corticotropin‐releasing hormone receptor gene and adult depression in the general population
Authors: Grabe Hans Jörgen , Schwahn Christian , Appel Katja , Mahler Jessie , Schulz Andrea , Spitzer Carsten , Fenske Kristin , Barnow Sven , Lucht Michael , Freyberger Harald Jürgen , John Ulrich , Teumer Alexander , Wallaschofski Henri , Nauck Matthias , Völzke Henry 
Published: October 2010

AbstractDysregulations of the hypothalamic‐pituitary‐adrenal (HPA) axis have been implicated in the pathogenesis of depressive disorders and the corticotropin‐releasing hormone (CRH) was found to modulate emotional memory consolidation. Recently, two studies have reported an interaction between childhood abuse and the TAT–haplotype of the CRH‐Receptor Gene (CRHR1) connecting childhood adversities and genetic susceptibility to adult depression. We tested the hypothesis of an interaction of childhood maltreatment with single nucleotide polymorphisms (SNPs) and haplotypes of theCRHR1gene not previously investigated. Caucasian subjects (n = 1,638) from the German general population (Study of Health in Pomerania, SHIP) were analyzed. As in the previous studies, childhood abuse and neglect were assessed with the Childhood Trauma Questionnaire (CTQ) and depression with the Beck Depression Inventory (BDI‐2). TheCRHR1‐SNPs were genotyped on the Affymetrix Genome‐Wide Human SNP Array 6.0 platform. We identified an interaction between the TAT–haplotype and childhood physical neglect. The interaction with physical neglect showed significant (P < 0.05) results in 23 of the 28 SNPs, with rs17689882 (P = 0.0013) reaching “gene‐wide” significance. Although we did not replicate the specific interaction of abuse and the TAT–haplotype of theCRHR1gene we confirmed the relevance of an interplay between variants within theCRHR1gene and childhood adversities in the modulation of depression in adults. The largest effect was found for rs17689882, a SNP previously not analyzed. Relevant sample differences between this and prior studies like lower BDI‐2 scores, less childhood maltreatment and higher psychosocial functioning may account for the differences in gene–environment interaction findings. © 2010 Wiley‐Liss, Inc.
Effects of the A(−115)G variant on CREB1 promoter activity in two brain cell lines: Interactions with gonadal steroids
Authors: Zubenko George S. , Hughes Hugh B. 
Published: October 2010

AbstractMajor depressive disorder (MDD) is a leading contributor to disease burden worldwide. Previous genetic studies have revealed significant evidence of linkage of the CREB1 region to mood disorders among women from families with recurrent, early‐onset MDD (RE‐MDD), a severe and familial subtype of MDD. Systematic resequencing of the CREB1 gene in affected members of these families has identified rare sequence variants at positions −656 and −115 that appear to cosegregate with unipolar mood disorders in two large multigenerational families and three small nuclear families, respectively. Results from previous transfection experiments that employed constructs containing the wild‐type or variant CREB1 promoters coupled to a reporter gene support the hypothesis that the A−656 allele contributes to the development of MDD in women by selectively increasing the activity of the CREB1 promoter in brain cell lines exposed to 17 β‐estradiol. Analogous transfection experiments described in the current study revealed that the G−115 promoter variant reduced promoter activity in CATH.a neuronal cells regardless of the hormonal environment, consistent with the observation that increased risk for unipolar mood disorders conferred by this allele was not limited by sex. The effects of CREB1 promoter variants on promoter activity, their influence on the development of mood disorders and related clinical features, and the interaction of their phenotypic expression with sex seem likely to be complex and allele‐specific rather than a general property of the CREB1 locus. © 2010 Wiley‐Liss, Inc.
Applying electrical resistivity tomography to the identification of endokarstic geometries in the Pleistocene Sites of the Sierra de Atapuerca (Burgos, Spain)
Authors: Ortega A.I. , Benito‐Calvo A. , Porres J. , Pérez‐González A. , Martín Merino M.A. 
Published: October 2010

AbstractIn this paper we have applied the electrical resistivity tomography (ERT) in order to prospect and to analyse the morphological and geological subsurface of the Torcas‐Cueva Mayor endokarst system (Sierra de Atapuerca). These works are essential to establish the development of the sedimentary infills where the Early and Middle Pleistocene archaeo‐palaeoanthropological sites of the Sierra de Atapuerca are located. The prospecting was based on the elaboration of 15 ERT sections, which were interpreted using topographic, archaeological, geological and geomorphological data. Through this procedure we have indentified the endokarst morphologies and the main lithological groups. The latter correspond to the Upper Cretaceous limestones and dolostones (> 1500 ohm m−1) and Neogene sediments and Quaternary valley infills (< 400 ohm m−1). The endokarst structures inside the Upper Cretaceous carbonates were related to empty cavities (> 1500 ohm m−1), passages filled with speleothems (400–1500 ohm m−1and with detrital materials (< 400 ohm m−1), such as the deposits of the Dolina, Elefante and Galería sites. The analysis of these subsurface structures shows that the karstic passages present a regular south–north development, starting with subsurface faults detected in the north margin of the main valley (Arlanzón River) and finishing along the Pico valley headwaters. These passages were cut off by the Pleistocene incision of the Sierra de Atapuerca minor valleys (e.g. Propiedad valley), forming entrances to caves that were occupied by hominids and fauna from Early Pleistocene times. Copyright © 2010 John Wiley & Sons, Ltd.
State‐feedback stabilization for stochastic high‐order nonlinear systems with SISS inverse dynamics
Authors: Liu Liang , Xie Xue‐Jun 
Published: October 2010

AbstractThis paper investigates the problem of state‐feedback control for a class of stochastic high‐order nonlinear systems with stochastic inverse dynamics. Under the assumption that the inverse dynamics of the subsystem are stochastic input‐to‐state stable (SISS), by extending through adding a power integrator technique, choosing an appropriate Lyapunov function and using the idea of changing supply function, a smooth state‐feedback controller is explicitly constructed to render the system globally asymptotically stable in probability and the states can be regulated to the origin. A simulation example is provided to show the effectiveness of the proposed scheme.Copyright © 2010 John Wiley and Sons Asia Pte Ltd and Chinese Automatic Control Society
A computational model for the probit‐based dynamic stochastic user optimal traffic assignment problem
Authors: Meng Qiang , Khoo Hooi Ling 
Published: October 2010

AbstractThis paper focuses on computational model development for the probit‐based dynamic stochastic user optimal (P‐DSUO) traffic assignment problem. We first examine a general fixed‐point formulation for the P‐DSUO traffic assignment problem, and subsequently propose a computational model that can find an approximated solution of the interest problem. The computational model includes four components: a strategy to determine a set of the prevailing routes between each origin–destination pair, a method to estimate the covariance of perceived travel time for any two prevailing routes, a cell transmission model‐based traffic performance model to calculate the actual route travel time used by the probit‐based dynamic stochastic network loading procedure, and an iterative solution algorithm solving the customized fixed‐point model. The Ishikawa algorithm is proposed to solve the computational model. A comparison study is carried out to investigate the efficiency and accuracy of the proposed algorithm with the method of successive averages. Two numerical examples are used to assess the computational model and the algorithm proposed. Results show that Ishikawa algorithm has better accuracy for smaller network despite requiring longer computational time. Nevertheless, it could not converge for larger network. Copyright © 2010 John Wiley & Sons, Ltd.
A new automated grading approach for computer programming
Authors: Liu Xiong'en 
Published: October 2010

AbstractThe current grading systems for computer programming assignments have taken correctness, efficiency, complexity, and maintainability into account. Of these four components, the most important measurement is the correctness. However, the existing grading systems still have some drawbacks. It is hard to measure college students' overall programming skills based only on their answers to a single form of programming questions. The author proposes a new approach by presenting multiple forms of computer programming questions, such as statement filling‐in, program modifying and algorithm designing, and by providing an automated grading algorithm to measure the correctness, time efficiency, space efficiency, complexity, and robustness. This proposed automated grading method has been employed successfully in the development of C programming and Delphi programming exam systems for Computer Application Ability Exam for College Students in Fujian. It has also been applied to the development of an online programming self‐testing system for Data Structure course which is offered by Fujian Agriculture and Forestry University. © 2010 Wiley Periodicals, Inc. Comput Appl Eng Educ 21: 484–490, 2013
Discursive deracialization in talk about asylum seeking
Authors: Goodman Simon , Burke Shani 
Published: October 2010

AbstractIn this paper we explore the extent to which ‘discursive deracialization’, the removal of ‘race’ from potentially racially motivated arguments, is taking place in talk about asylum seeking. A discourse analysis is conducted on the part of a corpus of data collected from focus groups with undergraduate students talking about asylum seeking, in which they were asked if they considered it to be racist to oppose asylum. We show that speakers use three arguments for opposing asylum that are explicitly framed as non‐racist: opposition is based on (1) economic reasons (2) religious grounds and the associated threat of terrorism and (3) the lack of asylum seekers' ability to integrate into British society. These findings are discussed with regard to the implications they have for our understanding of discursive deracialization in which it is shown that there is a common knowledge understanding, albeit one that needs qualifying, that opposition to asylum is not racist. Copyright © 2010 John Wiley & Sons, Ltd.
High‐Pressure Investigations under CO/H2 of Rhodium Complexes Containing Hemispherical Diphosphites
Authors: Sémeril David , Matt Dominique , Toupet Loïc , Oberhauser Werner , Bianchini Claudio 
Published: October 2010

AbstractThe two rhodium complexes [Rh(acac)(LR)] (LR=(S,S)‐5,11,17,23‐tetra‐tert‐butyl‐25,27‐di(OR)‐26,28‐bis(1,1′‐binaphthyl‐2,2′‐dioxyphosphanyloxy)calix[4]arene; 6: R=benzyl, 7: R=fluorenyl), each based on a hemispherical chelator forming a pocket about the metal centre upon chelation, are active in the hydroformylation of 1‐octene and styrene. As expected for this family of diphosphanes, both complexes resulted in remarkably high selectivity towards the linear aldehyde in the hydroformylation of 1‐octene (l/b≈15 for both complexes). Linear aldehyde selectivity was also observed when using styrene, but surprisingly only 6 displayed a marked preference for the linear product (l/b=12.4 (6) vs. 1.9 (7)). A detailed study of the structure of the complexes under CO or CO/H2 in toluene was performed by high‐pressure NMR (HP NMR) and FT‐IR (HP‐IR) spectroscopies. The spectroscopic data revealed that treatment of 6 with CO gave [Rh(acac)(CO)(η1‐Lbenzyl)] (8), in which the diphosphite behaves as a unidentate ligand. Subsequent addition of H2 to the solution resulted in a well‐defined chelate complex with the formula [RhH(CO)2(Lbenzyl)] (9). Unlike 6, treatment of complex 7 with CO only led to ligand dissociation and concomitant formation of [Rh(acac)(CO)2], but upon addition of H2 a chelate complex analogous to 9 was formed quantitatively. In both [RhH(CO)2(LR)] complexes the diphosphite adopts the bis‐equatorial coordination mode, a structural feature known to favour the formation of linear aldehydes. As revealed by variable‐temperature NMR spectroscopy, these complexes show the typical fluxionality of trigonal bipyramidal [RhH(CO)2(diphosphane)] complexes. The lower linear selectivity of 7 versus 6 in the hydroformylation of styrene was assigned to steric effects, due to the pocket in which the catalysis takes place being less adapted to accommodate CO or larger olefins and, therefore, possibly leading to facile ligand decoordination. This interpretation was corroborated by an X‐ray structure determination carried out for 7.
Modeling and Biological Investigations of an Unusual Behavior of Novel Synthesized Acridine‐Based Polyamine Ligands in the Binding of Double Helix and G‐Quadruplex DNA
Authors: Bazzicalupi Carla , Chioccioli Matteo , Sissi Claudia , Porcù Elena , Bonaccini Claudia , Pivetta Claudia , Bencini Andrea , Giorgi Claudia , Valtancoli Barbara , Melani Fabrizio , Gratteri Paola 
Published: October 2010

AbstractThree novel 2,7‐substituted acridine derivatives were designed and synthesized to investigate the effect of this functionalization on their interaction with double‐stranded and G‐quadruplex DNA. Detailed investigations of their ability to bind both forms of DNA were carried out by using spectrophotometric, electrophoretic, and computational approaches. The ligands in this study are characterized by an open‐chain (L1) or a macrocyclic (L2, L3) framework. The aliphatic amine groups in the macrocycles are joined by ethylene (L2) or propylene chains (L3). L1 behaved similarly to the lead compound m‐AMSA, efficiently intercalating into dsDNA, but stabilizing G‐quadruplex structures poorly, probably due to the modest stabilization effect exerted by its protonated polyamine chains. L2 and L3, containing small polyamine macrocyclic frameworks, are known to adopt a rather bent and rigid conformation; thus they are generally expected to be sterically impeded from recognizing dsDNA according to an intercalative binding mode. This was confirmed to be true for L3. Nevertheless, we show that L2 can give rise to efficient π–π and H‐bonding interactions with dsDNA. Additionally, stacking interactions allowed L2 to stabilize the G‐quadruplex structure: using the human telomeric sequence, we observed the preferential induction of tetrameric G‐quadruplex forms. Thus, the presence of short ethylene spacers seems to be essential for obtaining a correct match between the binding sites of L2 and the nucleobases on both DNA forms investigated. Furthermore, current modeling methodologies, including docking and MD simulations and free energy calculations, provide structural evidence of an interaction mode for L2 that is different from that of L3; this could explain the unusual stabilizing ability of the ligands (L2>L3>L1) toward G‐quadruplex that was observed in this study.
Equivalence of the time‐domain matched filter and the spectral‐domain matched filter in one‐dimensional NMR spectroscopy
Authors: Spencer Richard G. 
Published: October 2010

AbstractA type of “matched filter” (MF), used extensively in the processing of one‐dimensional spectra, is defined by multiplication of a free‐induction decay (FID) by a decaying exponential with the same time constant as that of the FID. This maximizes, in a sense to be defined, the signal‐to‐noise ratio (SNR) in the spectrum obtained after Fourier transformation. However, a different entity known also as the MF was introduced by van Vleck in the context of pulse detection in the 1940's and has become widely integrated into signal processing practice. These two types of MFs appear to be quite distinct. In the NMR case, the “filter”, that is, the exponential multiplication, is defined by the characteristics of, and applied to, a time domain signal to achieve improved SNR in the spectral domain. In signal processing, the filter is defined by the characteristics of a signal in the spectral domain, and applied to improve the SNR in the temporal (pulse) domain. We reconcile these two distinct implementations of the MF, demonstrating that the NMR “MF” is a special case of the MF more rigorously defined in the signal processing literature. In addition, two limitations on the use of the MF are highlighted. First, application of the MF distorts resonance ratios as defined by amplitudes, although not as defined by areas. Second, the MF maximizes SNR with respect to resonance amplitude, while intensity is often more appropriately defined by area. Maximizing the SNR with respect to area requires a somewhat different approach to matched filtering. © 2010 Wiley Periodicals, Inc. Concepts Magn Reson Part A 36A: 255–265, 2010.
Improved outcome of patients with low‐ and intermediate‐risk cytogenetics acute myeloid leukemia (AML) in first relapse with gemtuzumab and cytarabine versus cytarabine
Authors: Prebet Thomas , Etienne Anne , Devillier Raynier , Romeo Emilie , Charbonnier Aude , D'incan Evelyne , Esterni Benjamin , Arnoulet Christine , Blaise Didier , Vey Norbert 
Published: October 2010

AbstractBACKGROUND:Acute myeloid leukemia (AML) in first relapse is associated with a poor outcome even when treated with intermediate‐ to high‐dose cytarabine (IHDAraC). Gemtuzumab ozogamycin (GO) used as a single agent has clinical activity in relapsed and refractory AML. Various combination regimens of GO have been developed, but few data are available regarding their efficacy compared with IHDAraC‐based regimens.METHODS:The authors performed a retrospective analysis of response and survival in 90 AML patients in first relapse treated with either IHDAraC (n = 56) or IHDAraC + GO (n = 34). Patient characteristics of the two groups were comparable.RESULTS:Median follow‐up was 37 months. Compared with IHDAraC, IHDAraC + GO induction was associated with a better response rate (68% vs 45%, P = .04), a better overall survival (median, 35 months vs 6 months, P = .001), and a better event‐free survival (24 months vs 6 months, P = .002). This effect was limited to patients with low‐risk and intermediate‐risk cytogenetics. In multivariate analysis, age, cytogenetic risk, first complete remission duration, and the use of IHDAraC + GO were independently associated with better results.CONCLUSIONS:This study showed that the addition of GO to IHDAraC is associated with a better efficacy for patients in first relapse of AML with low‐ or intermediate‐risk cytogenetics. Prospective controlled studies of GO in this population are warranted. Patients with high‐risk cytogenetics should be offered investigational new drugs. Cancer 2011. © 2010 American Cancer Society.
Using claims‐based measures to predict performance status score in patients with lung cancer
Authors: Salloum Ramzi G. , Smith Thomas J. , Jensen Gail A. , Lafata Jennifer Elston 
Published: October 2010

AbstractBACKGROUND:Performance status (PS) is a good prognostic factor in lung cancer and is used to assess chemotherapy appropriateness. Researchers studying chemotherapy use are often hindered by the unavailability of PS in automated data sources. To the authors' knowledge, no attempts have been made to estimate PS using claims‐based measures. The current study explored the ability to estimate PS using routinely available measures.METHODS:A cohort of insured patients aged ≥50 years who were diagnosed with American Joint Committee on Cancer stage II through IV lung cancer between 2000 and 2007 was identified via a tumor registry (n = 552). PS was abstracted from medical records. Automated medical and pharmaceutical claims from the year preceding diagnosis were linked to tumor registry data. A logistic regression model was fit to estimate good versus poor PS in a random half of the sample. C statistics, sensitivity, specificity, and R2 were used to compare the predictive ability of models that included demographic factors, comorbidity measures, and claims‐based utilization variables. Model fit was evaluated in the other half of the sample.RESULTS:PS was available in 80% of medical records. The multivariable regression model predicted good PS with high sensitivity (0.88 or 0.94 depending on how good PS was defined), but moderate specificity (0.45 or 0.32) with a 0.50 prediction cutoff, and good sensitivity (0.64 or 0.83) and specificity (0.69 or 0.55) when the cutoff was 0.70. The goodness‐of‐fit c statistic was 0.76 or 0.78.CONCLUSIONS:PS can be estimated, with some accuracy, using claims‐based measures. Emphasis should be placed on documenting PS in medical records and tumor registries. Cancer 2011. © 2010 American Cancer Society