bluuebunny/crossref_metadata_2025_split huggingface dataset:
Understanding of Molecular Substructures that Contribute to hERG K+ Channel Blockade: Synthesis and Biological Evaluation of E‐4031 Analogues
Authors: Vilums Maris , Overman Jeroen , Klaasse Elisabeth , Scheel Olaf , Brussee Johannes , IJzerman Adriaan P. 
Published: September 2011

AbstractCardiotoxicity is a common side effect of a large variety of drugs that is often caused by off‐target human ether‐à‐go‐go‐related gene (hERG) potassium channel blockade. In this study, we designed and synthesized a series of derivatives of the class III antiarrhythmic agent E‐4031. These compounds where evaluated in a radioligand binding assay and automated patch clamp assay to establish structure–activity relationships (SAR) for their inhibition of the hERG K+ channel. Structural modifications of E‐4031 were made by altering the peripheral aromatic moieties with a series of distinct substituents. Additionally, we synthesized several derivatives with a quaternary nitrogen and modified the center of the molecule by introduction of an additional nitrogen and deletion of the carbonyl oxygen. Some modifications caused a great increase in affinity for the hERG K+ channel, while other seemingly minor changes led to a strongly diminished affinity. Structures with quaternary amines carrying an additional aromatic moiety were found to be highly active in radioligand binding assay. A decrease in affinity was achieved by introducing an amide functionality in the central scaffold without directly interfering with the pKa of the essential basic amine. The knowledge gained from this study could be used in early stages of drug discovery and drug development to avoid or circumvent hERG K+ channel blockade, thereby reducing the risk of cardiotoxicity, related arrhythmias and sudden death.
A simple, versatile valve model for use in lumped parameter and one‐dimensional cardiovascular models
Authors: Mynard J. P. , Davidson M. R. , Penny D. J. , Smolich J. J. 
Published: September 2011

SUMMARYLumped parameter and one‐dimensional models of the cardiovascular system generally employ ideal cardiac and/or venous valves that open and close instantaneously. However, under normal or pathological conditions, valves can exhibit complex motions that are mainly determined by the instantaneous difference between upstream and downstream pressures. We present a simple valve model that predicts valve motion on the basis of this pressure difference, and can be used to investigate not only valve pathology, but a wide range of cardiac and vascular factors that are likely to influence valve motion. Copyright © 2011 John Wiley & Sons, Ltd.
The affective feelings of colored typefaces
Authors: Lee Wen‐Yuan , Pai Shao‐Yang 
Published: September 2011

AbstractThis study aims to explore the relation of affective feelings to typefaces and colors. Two experiments were conducted. The first experiment used 74 typefaces to investigate the affective feelings of typefaces. The second experiment used 72‐colored typefaces to investigate the influence of both colors and typefaces on affective feelings. The results showed the affective feelings for typefaces can be described by appearance and evaluation factors. The characteristic of serif and the print/handwriting look were found to be the criteria classifying the typefaces. Furthermore, the regression models for eight affective feelings were developed. These models showed that the typefaces were more influential than colors on the feelings of “complex–simple,” “beautiful–ugly,” “luxury–plain,” “active–passive,” “causal–regular,” and “like–dislike.” In comparison with typeface, color was more influential on “friendly–serious” and “soft–hard” feelings. © 2011 Wiley Periodicals, Inc. Col Res Appl, 2012
On the relationship between wavelength and perceived hue
Authors: Kuehni Rolf G. 
Published: September 2011

AbstractUnlike in the case of sound where there is a compressed but straightforward relationship between frequency of sound waves and the perceived pitch, in the case of color the relationship is highly nonlinear, as first pointed out by Ostwald in 1916. In this article, the relationship between the perceptual Munsell hue scale and the related dominant wavelengths of the color chips involved is investigated. A hypothesis is proposed according to which the immediate cause of the nonlinearity can be found in the relative activation of the kinds of chromatically opponent functions shown to exist in neurons of the lateral geniculate nuclei. However, at this time, the relationship is only correlational, given the lack of deeper understanding of the relationship between the physiological operation of the color vision system and conscious experiences of color. © 2011 Wiley Periodicals, Inc. Col Res Appl, 2011;
Closed‐form analysis of multibranch switched diversity with noncoherent and differentially coherent detection
Authors: Morales‐Jiménez David , Paris José F. , Wong Kai‐Kit 
Published: September 2011

SUMMARYExact closed‐form analytical expressions are derived for the average bit error probability of multibranch switched diversity systems over independent and identically Nakagami‐m distributed fading channels. Practical schemes that use noncoherent or differentially coherent symbol detection are considered. The general bit error probability expression derived in this paper includes as particular cases the following signaling formats: orthogonal binary signaling, correlated binary signaling, differential phase‐shift keying, and differential quadrature phase‐shift keying. Finally, we apply our analytical results to study the impact of the switching threshold selection on the system performance. Copyright © 2011 John Wiley & Sons, Ltd.
Stereoselective Synthesis of Aza Analogues of Isoaltholactone and Goniothalesdiol – New Applications of the Heck–Matsuda Reaction
Authors: Moro Angélica Venturini , Rodrigues dos Santos Marcelo , Correia Carlos Roque D. 
Published: September 2011

AbstractThe stereoselective synthesis of nitrogen analogues of biologically active isoaltholactone and goniothalesdiol are described. The successful strategy employed a Heck–Matsuda reaction between a chiral endocyclic enecarbamate bearing an ester functionality and arenediazonium tetrafluoroborates in a divergent approach at an early stage of the synthesis. Several aspects related to this critical arylation reaction are discussed to highlight structural features that affect the outcome of the arylation process. The synthesis of (–)‐aza‐isoaltholactone 6 was successfully accomplished in nine steps from the starting enecarbamate. We also performed the synthesis of the new fully substituted pyrrolidine (–)‐(2R,3R,4S,5S)‐1‐(tert‐butoxycarbonyl)‐3,4‐dihydroxy‐5‐phenylpyrrolidin‐2‐ylacrylic acid 28, which is a potential advanced intermediate in the route to aza‐altholactone. Moreover, the synthesis of a new nitrogen analogue of goniothalesdiol (+)‐33 was accomplished from the protected dihydroxypyrrolidine (–)‐27, obtained from an attempted synthesis of aza‐altholactone.
Toxicity of the fluoroquinolone antibiotics enrofloxacin and ciprofloxacin to photoautotrophic aquatic organisms
Authors: Ebert Ina , Bachmann Jean , Kühnen Ute , Küster Anette , Kussatz Carola , Maletzki Dirk , Schlüter Christoph 
Published: September 2011

Abstract
The present study investigated the growth inhibition effect of the fluoroquinolone antibiotics enrofloxacin and ciprofloxacin on four photoautotrophic aquatic species: the freshwater microalga Desmodesmus subspicatus, the cyanobacterium Anabaena flos-aquae, the monocotyledonous macrophyte Lemna minor, and the dicotyledonous macrophyte Myriophyllum spicatum. Both antibiotics, which act by inhibiting the bacterial DNA gyrase, demonstrated high toxicity to A. flos-aquae and L. minor and moderate to slight toxicity to D. subspicatus and M. spicatum. The cyanobacterium was the most sensitive species with median effective concentration (EC50) values of 173 and 10.2 µg/L for enrofloxacin and ciprofloxacin, respectively. Lemna minor proved to be similarly sensitive, with EC50 values of 107 and 62.5 µg/L for enrofloxacin and ciprofloxacin, respectively. While enrofloxacin was more toxic to green algae, ciprofloxacin was more toxic to cyanobacteria. Calculated EC50s for D. subspicatus were 5,568 µg/L and &gt;8,042 µg/L for enrofloxacin and ciprofloxacin, respectively. These data, as well as effect data from the literature, were compared with predicted and reported environmental concentrations. For two of the four species, a risk was identified at ciprofloxacin concentrations found in surface waters, sewage treatment plant influents and effluents, as well as in hospital effluents. For ciprofloxacin the results of the present study indicate a risk even at the predicted environmental concentration. In contrast, for enrofloxacin no risk was identified at predicted and measured concentrations. Environ. Toxicol. Chem. 2011;30:2786–2792. © 2011 SETAC
Ecotoxicological impact of the fungicide tebuconazole on an aquatic decomposer-detritivore system
Authors: Zubrod Jochen P , Bundschuh Mirco , Feckler Alexander , Englert Dominic , Schulz Ralf 
Published: September 2011

Abstract
Leaf litter breakdown is a fundamental process in aquatic ecosystems that is realized by microbial decomposers and invertebrate detritivores. Although this process may be adversely affected by fungicides, among other factors, no test design exists to assess combined effects on such decomposer–detritivore systems. Hence, the present study assessed effects of the model fungicide tebuconazole (65 µg/L) on the conditioning of leaf material (by characterizing the associated microbial community) as well as the combined effects (i.e., direct toxicity and food quality-related effects (=indirect)) on the energy processing of the leaf-shredding amphipod Gammarus fossarum using a five-week semistatic test design. Gammarids exposed to tebuconazole produced significantly less feces (∼20%), which in turn significantly increased their assimilation (∼30%). Moreover, a significantly reduced lipid content (∼20%) indicated lower physiological fitness. The conditioning process was altered as well, which was indicated by a significantly reduced fungal biomass (∼40%) and sporulation (∼30%) associated with the leaf material. These results suggest that tebuconazole affects both components of the investigated decomposer-detritivore system. However, adverse effects on the level of detritivores cannot be explicitly attributed to direct or indirect pathways. Nevertheless, as the endpoints assessed are directly related to leaf litter breakdown and associated energy transfer processes, the protectiveness of environmental risk assessment for this ecosystem function may be more realistically assessed in future studies by using this or comparable test designs. Environ. Toxicol. Chem. 2011;30:2718–2724. © 2011 SETAC
Multiple stressors and complex life cycles: Insights from a population-level assessment of breeding site contamination and terrestrial habitat loss in an amphibian
Authors: Salice Christopher J , Rowe Christopher L , Pechmann Joseph H.K , Hopkins William A 
Published: September 2011

Abstract
Understanding the effects of chemical contaminants on natural populations is challenging, as multiple anthropogenic and natural stressors may individually and interactively influence responses. Population models can be used to evaluate the impacts of multiple stressors and to provide insight into population-level effects and/or data gaps. For amphibians with complex life cycles, population models may be useful in understanding impacts of stressors that are unique to the habitat type (aquatic, terrestrial) and that operate at different times in the life cycle. We investigated the population-level effects of aquatic contaminants (coal combustion residues, CCR) and terrestrial habitat loss on the eastern narrowmouth toad, Gastrophryne carolinensis, using existing empirical data that demonstrated negative reproductive and developmental effects of CCR and a series of population models that incorporated density dependence and environmental stochasticity. Results of deterministic models indicated that when terrestrial habitat was abundant, CCR-exposed toads had a larger population size compared to the reference population as a result of reduced density-dependent effects on larval survival. However, when stochasticity in the form of catastrophic reproductive failure was included, CCR-exposed toads were more susceptible to decline and extinction compared to toads from the reference populations. The results highlight the complexities involved in assessing the effects of anthropogenic factors on natural populations, especially for species that are exposed to multiple biotic and abiotic stressors during different periods in the life cycle. Environ. Toxicol. Chem. 2011;30:2874–2882. © 2011 SETAC
Using extreme phenotype sampling to identify the rare causal variants of quantitative traits in association studies
Authors: Li Dalin , Lewinger Juan Pablo , Gauderman William J. , Murcray Cassandra Elizabeth , Conti David 
Published: September 2011

AbstractVariants identified in recent genome‐wide association studies based on the common‐disease common‐variant hypothesis are far from fully explaining the hereditability of complex traits. Rare variants may, in part, explain some of the missing hereditability. Here, we explored the advantage of the extreme phenotype sampling in rare‐variant analysis and refined this design framework for future large‐scale association studies on quantitative traits. We first proposed a power calculation approach for a likelihood‐based analysis method. We then used this approach to demonstrate the potential advantages of extreme phenotype sampling for rare variants. Next, we discussed how this design can influence future sequencing‐based association studies from a cost‐efficiency (with the phenotyping cost included) perspective. Moreover, we discussed the potential of a two‐stage design with the extreme sample as the first stage and the remaining nonextreme subjects as the second stage. We demonstrated that this two‐stage design is a cost‐efficient alternative to the one‐stage cross‐sectional design or traditional two‐stage design. We then discussed the analysis strategies for this extreme two‐stage design and proposed a corresponding design optimization procedure. To address many practical concerns, for example measurement error or phenotypic heterogeneity at the very extremes, we examined an approach in which individuals with very extreme phenotypes are discarded. We demonstrated that even with a substantial proportion of these extreme individuals discarded, an extreme‐based sampling can still be more efficient. Finally, we expanded the current analysis and design framework to accommodate the CMC approach where multiple rare‐variants in the same gene region are analyzed jointly. Genet. Epidemiol. 2011. © 2011 Wiley Periodicals, Inc. 35:790‐799, 2011
Change in cognitive functioning in depressed older adults following treatment with sertraline or nortriptyline
Authors: Culang‐Reinlieb Michelle E. , Sneed Joel R. , Keilp John G. , Roose Steven P. 
Published: September 2011

ObjectiveThe aim of this study was to compare the impact of nortriptyline to sertraline on change in cognitive functioning in depressed older adults.MethodsWe used pre–post neuropsychological data collected as part of a 12‐week medication trial comparing sertraline to nortriptyline in the treatment of older adults with non‐psychotic, unipolar major depression to examine change in cognitive functioning. Neuropsychological assessments included mental status (Mini‐Mental Status Exam), psychomotor speed (Purdue Pegboard), attention (Continuous Performance Test, Trail Making Test A), executive functioning (Stroop Color/word Test, Trail Making Test B), and memory (Buschke Selective Reminding Test).ResultsWithin treatment groups, patients treated with sertraline improved only on verbal learning. This change did not depend on responder status. Between treatment groups, patients treated with sertraline improved more in verbal learning compared with patients treated with nortriptyline. Looking at change in cognition as a function of medication condition and responder status revealed that sertraline responders improved more in verbal learning compared with nortriptyline responders but not more than sertraline non‐responders or nortriptyline non‐responders. Nortriptyline responders were the only treatment by responder status group to show no improvement in verbal learning from baseline to endpoint.ConclusionsUnexpectedly, nortriptyline responders showed no improvement in verbal learning as compared with patients treated with sertraline or nortriptyline non‐responders. However, given the small sample sizes and number of statistical tests (potential for type 1 error), replication is warranted. Copyright © 2011 John Wiley & Sons, Ltd.
Anxious symptoms and cognitive function in non‐demented older adults: an inverse relationship
Authors: Stillman Ashley N. , Rowe Kelly C. , Arndt Stephan , Moser David J. 
Published: September 2011

BackgroundThe goals of this study were to determine the relationship between anxious symptoms and cognitive functioning in a non‐demented, community‐dwelling older adults sample (n = 48), and to determine the effect of depressive symptoms upon this relationship.MethodsAnxious and depressive symptoms were assessed using the Symptom Checklist 90—Revised. Cognitive functioning was assessed with the Repeatable Battery for the Assessment of Neuropsychological Status.ResultsResults indicated that although both cognitive functioning and anxious symptoms were within normal limits in this sample, anxious symptoms showed a significant, inverse relationship with global cognitive function [r(47) = −0.400, p = 0.005]. In addition, specific relationships were noted between severity of anxious symptoms and visuospatial/constructional ability as well as immediate and delayed memory. With regard to the secondary objective, both anxiety and depressive symptoms together accounted for the highest level of variance [R2 = 0.175, F(2, 45) = 4.786, p = 0.013] compared with anxiety [R2(47) = 0.160, p = 0.005] and depression [R2(47) = 0.106, p = 0.024] alone. Nevertheless, neither anxious nor depressive symptoms emerged as a unique correlate with cognitive ability [r(47) = −0.278, p = 0.058; r(48) = −0.136, p = 0.363, respectively].ConclusionThis study demonstrates that subthreshold anxiety symptoms and cognitive functioning are significantly related even among generally healthy older adults whose cognitive ability and severity of anxious symptoms are within broad normal limits. These findings have implications both for clinical care of older patients, as well as for cognitive research studies utilizing this population. Copyright © 2011 John Wiley & Sons, Ltd.
Facile sulfur‐assisted carbonylation of diaminoresorcinol with carbon monoxide
Authors: Mizuno Takumi , Nakai Takeo , Mihara Masatoshi , Ito Takatoshi 
Published: September 2011

Abstract4,6‐Diaminoresorcinol, which is a raw material of ZYLON (PBO fiber), has an instability in air atmosphere. Therefore, very stable benzo[1,2‐d:5,4‐d']bis‐2(3H)‐oxazolone recognized a useful equivalent of 4,6‐diaminoresorcinol during the stages of production, storage, and transportation. By combining the sulfur‐assisted carbonylation of 4,6‐diaminoresorcinol dihydrochloride with carbon monoxide and triethylamine under 0.1 MPa at 20°C for 4 h in DMF with the oxidation of resulting hydrogen sulfide salt with molecular oxygen for 2 h, benzo‐[1,2‐d:5,4‐d']bis‐2(3H)‐oxazolone was obtained in a quantitative yield. Also, carbonylation of 2,5‐diaminohydroquinone dihydrochloride and 2,5‐diamino‐1,4‐benzenedithiol dihydrochloride was smoothly performed to give benzo[1,2‐d:4,5‐d']bis‐2(3H)‐oxazolone and benzo[1,2‐d:4,5‐d']bis‐2(3H)‐ thiazolone, respectively, in good to excellent yields under similar reaction conditions. Furthermore, 2,6‐dimercaptobenzo[1,2‐d:5,4‐d']bisoxazole, which is another equivalent of 4,6‐diaminoresorcinol, was obtained in excellent yield by the thiocarbonylation of 4,6‐diaminoresorcinol dihydro‐chloride with carbon disulfide in the presence of 1‐methylpyrrolidine at 20°C for 24 h in DMF. © 2011 Wiley Periodicals, Inc. Heteroatom Chem 23:111–116, 2012; View this article online at wileyonlinelibrary.com. DOI 10.1002/hc.20746
Structural diversity in the coordination of 1,4‐dihydro‐1,4‐diarsinine as a cyclic ditopic organoarsenic ligand to metal ions
Authors: Arita Manabu , Naka Kensuke , Morisaki Yasuhiro , Chujo Yoshiki 
Published: September 2011

AbstractA number of different complexation structures of cis‐1,4‐dihydro‐1,4‐dimethyl‐2,3,5,6‐tetrakis(t‐butoxycarbonyl)‐1,4‐diarsinine (cis‐DHDAtBu) with gold(I) and iridium(III) were synthesized and characterized by 1H, 13C NMR spectra, X‐ray crystallography, and elemental analysis. Mono‐ and di‐nuclear gold(I) chloride complexes with cis‐DHDAtBu were obtained by simple addition of gold(I) chloride to cis‐DHDAtBu. A hetero‐trinuclear gold‐platinum‐gold complex (PtAu2Cl4(cis‐DHDAtBu)2) was obtained by complexation of a mononuclear platinum(II) complex (trans‐PtCl2(cis‐DHDAtBu)2), which was obtained by complexation of cis‐DHDAtBu with a half‐equimolar amount of PtCl2(PhCN)2, with a twice‐equimolar amount of gold(I) chloride. An iridium(III) complex with cis‐DHDAtBu (IrCl3(cis‐DHDAtBu)2) was prepared from hydrated iridium(III) chloride and cis‐DHDAtBu. The complex comprises a five‐membered chelate cis‐DHDAtBu and an usual monodentate cis‐DHDAtBu. The interior angles at around the arsenic and the As–C—C bond angles were significantly varied from 113.4° to 129.4° in the present crystal. These observations suggest that the flexibility of the bond angles at around the arsenic center is inherent property in the present organoarsenic compounds. © 2011 Wiley Periodicals, Inc. Heteroatom Chem 23:16–26, 2012; View this article online at wileyonlinelibrary.com. DOI 10.1002/hc.20747
PPh3‐catalyzed knoevenagel condensation: A facile synthesis of 5‐(1H‐indol‐3‐yl)Meth‐ ylene)‐2, 2‐Dimethyl‐1, 3‐Dioxane‐4, 6‐dione, and their N‐alkyl derivatives by using peg‐600 as the reaction medium
Authors: Venkatanarayana Muvvala , Kumar Dubey Pramod 
Published: September 2011

AbstractTriphenylphosphine (TPP) has been utilized as a novel and efficient catalyst for the Knoevenagel condensation of indole‐3‐carboxaldehydes 1(a–e), 1‐methyl‐1H‐indole‐3‐carboxaldehydes 4(a–e), and 1‐ethyl‐1H‐indole‐3‐carboxaldehydes 6(a–e) with the active methylene compound, that is, meldrum's acid (2), to afford substituted derivatives 5‐((1H‐indol‐3‐yl) methylene)‐2,2‐dimethyl‐1,3‐dioxane‐4,6‐dione 3(a–e), 2,2‐dimethyl‐5‐((1‐methyl‐1H‐indol‐3‐yl)methylene)‐1,3‐dioxane‐4,6‐dione 5(a–e), and 2,2‐dimethyl‐5‐((1‐ethyl‐1H‐indol‐3‐yl)methylene)‐1,3‐dioxane‐4,6‐dione 7(a–e), respectively, in ethanol medium at RT just within 1 h in excellent yields. The products 3(a–e) were reacted independently with alkylating agents, that is, DMS and DES in the presence of PEG‐600 as an efficient and green solvent, to afford the corresponding N‐substituted methyl and ethyl derivatives 5(a–e) and 7(a–e), respectively. © 2011 Wiley Periodicals, Inc. Heteroatom Chem 23:41–48, 2012; View this article online at wileyonlinelibrary.com. DOI 10.1002/hc.20750