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Mach UR Hackling AE Perachon S Ferry S Wermuth CG Schwartz JC Sokoloff P Stark H 《Chembiochem : a European journal of chemical biology》2004,5(4):508-518
Based on N-alkylated 1,2,3,4-tetrahydroisoquinoline derivatives, which are structurally related to the partial agonist BP 897, a series of novel, selective dopamine D3 receptor antagonists has been synthesised. Derivatisation included changes in the arylamide moiety and the tetrahydroisoquinoline substructure leading to compounds with markedly improved selectivities and affinities in the low nanomolar concentration range. From the 55 structures presented here, (E)-3-(4-iodophenyl)-N-(4-(1,2,3,4-tetrahydroisoquinolin-2-yl)butyl)acrylamide (51) has high affinity (Ki(hD3)=12 nM) and a 123-fold preference for the D3 receptor relative to the D2 receptor subtype. Its pharmacological profile offers the prospect of a novel radioligand as a tool for various dopamine D3-receptor-related in vitro and in vivo investigations. 相似文献
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This paper presents a new circuit architecture for turbo decoding, which achieves ultra high data rates when using product codes as error correcting codes. This architecture is able to decode product codes using binary BCH or m-ary Reed Solomon component codes. The major advantage of our full-parallel architecture is that it enables the memory block between each half-iteration to be removed. In fact, the proposed architecture opens the way to numerous applications such as optical transmission. In particular, our block turbo decoding architecture can support optical transmission at data rates above Gbit/s 相似文献
15.
Vasily Smirnov Olivier Grunewald Jean Muller Christina Zeitz Carolin D. Obermaier Aurore Devos Valrie Pelletier Batrice Bocquet Camille Andrieu Jean-Louis Bacquet Elodie Lebredonchel Saddek Mohand-Saïd Sabine Defoort-Dhellemmes Jos-Alain Sahel Hlne Dollfus Xavier Zanlonghi Isabelle Audo Isabelle Meunier Elise Boulanger-Scemama Claire-Marie Dhaenens 《International journal of molecular sciences》2021,22(12)
Variants of the TTLL5 gene, which encodes tubulin tyrosine ligase-like family member five, are a rare cause of cone dystrophy (COD) or cone-rod dystrophy (CORD). To date, only a few TTLL5 patients have been clinically and genetically described. In this study, we report five patients harbouring biallelic variants of TTLL5. Four adult patients presented either COD or CORD with onset in the late teenage years. The youngest patient had a phenotype of early onset severe retinal dystrophy (EOSRD). Genetic analysis was performed by targeted next generation sequencing of gene panels and assessment of copy number variants (CNV). We identified eight variants, of which six were novel, including two large multiexon deletions in patients with COD or CORD, while the EOSRD patient harboured the novel homozygous p.(Trp640*) variant and three distinct USH2A variants, which might explain the observed rod involvement. Our study highlights the role of TTLL5 in COD/CORD and the importance of large deletions. These findings suggest that COD or CORD patients lacking variants in known genes may harbour CNVs to be discovered in TTLL5, previously undetected by classical sequencing methods. In addition, variable phenotypes in TTLL5-associated patients might be due to the presence of additional gene defects. 相似文献
16.
Mitch J. Duncan Camille Short Mahbub Rashid Nicoleta Cutumisu Corneel Vandelanotte Ronald C. Plotnikoff 《Building Research & Information》2015,43(5):646-658
Office workers are commonly targeted in interventions to modify their sitting behaviour, yet there is limited evidence of the correlates of breaks in sitting to inform intervention development. This study identifies the individual, workplace and spatial configuration correlates of the frequency of breaks in sitting (number/hour) in office workers (n?=?5531) stratified by office type (private-enclosed, shared, open plan). All behaviours and potential correlates were measured via self-report using an online cross-sectional survey. Regression analyses revealed age was the only socio-demographic characteristic associated with frequency of breaks in sitting in all office types. Greater job autonomy and local connectivity were positively associated with frequency of breaks in sitting in shared and open-plan offices. In open-plan offices co-worker proximity was negatively associated with frequency of breaks in sitting. Co-worker visibility was positively associated with frequency of breaks in sitting in all office types. This study demonstrates that individual, workplace and spatial configuration factors are all associated with the frequency of breaks in sitting and that these relationships differ by office type. These observations extend prior studies that have only examined correlates at a single level (e.g. the individual). This evidence could be useful to guide future interventions in the design of workplaces to increase breaks in sitting and workers’ physical activity. 相似文献
17.
In the Closing Remarks at the Symposium on 'Frontiers in Bioorganic Chemistry' (Friday, February 6, 2009, Pharmacenter, University of Basel) in honour of Daniel Bellus, his arrival in Zürich in fall 1967 and especially his postdoctoral work at the Laboratorium für Organische Chemie at the Eidgen?ssische Technische Hochschule (ETH) in Zürich throughout the year 1967/68 were mentioned. In his most remarkable paper (published in 1969 in Helv. Chim. Acta), the photochemistry of the alpha,beta-unsaturated cyclohexenones O-acetyl-testosterone and 10-methy-delta1,9-octalon-(2) is described in detail. Change of solvent leads to lowering or increasing of the n,pi*- and (pi,pi*)-triplet energies, resulting in a crossing of the two energy levels. Personal remarks on Daniel Bellus and warmest thanks to him, to Profs. Beat Ernst and Bernd Giese (the organizers of the symposium) and to all the speakers concluded this most special event. 相似文献
18.
Patrick DallaireAuthor Vitae Camille Besse Author VitaeBrahim Chaib-draa Author Vitae 《Neurocomputing》2011,74(11):1945-1955
Most formulations of supervised learning are often based on the assumption that only the outputs data are uncertain. However, this assumption might be too strong for some learning tasks. This paper investigates the use of Gaussian processes to infer latent functions from a set of uncertain input-output examples. By assuming Gaussian distributions with known variances over the inputs-outputs and using the expectation of the covariance function, it is possible to analytically compute the expected covariance matrix of the data to obtain a posterior distribution over functions. The method is evaluated on a synthetic problem and on a more realistic one, which consist in learning the dynamics of a cart-pole balancing task. The results indicate an improvement of the mean squared error and the likelihood of the posterior Gaussian process when the data uncertainty is significant. 相似文献
19.
In-situ hardened properties of underwater concrete (UWC) are affected by washout loss and water infiltration occurring during the casting and post-casting stages. This paper evaluates the suitability of the falling-head method determined using a permeameter cell to assess water infiltration or, permeability (k), in freshly mixed UWC. Correlations between k and washout loss determined using the CRD C61 test method are established. The paper also seeks to quantify the coupled effect of washout loss and water infiltration on the drop in UWC compressive strength. Test results showed that Darcy’s law is valid to evaluate water permeability in UWC. The k and washout loss values are found to be well correlated within each other. UWC mixtures subjected to washout or water infiltration exhibited lower compressive strengths, as compared to reference concrete sampled in dry conditions. The drop in UWC strength was attributed to a combination of factors including washout loss of cementitious phase together with relative increases in aggregate concentration and specified water-to-cement ratio. 相似文献
20.
Nicolas von Solms Camille O. Anderson Harvey W. Blanch John M. Prausnitz 《American Institute of Chemical Engineers》2002,48(6):1292-1300
With saline water as the continuous medium, a two-component McMillan-Mayer equation of state is used to describe liquid–liquid phase equilibria in a two-protein system. The equation of state is based on a hard-sphere reference with perturbations introduced through a potential of mean force to account for electrostatic forces and for attraction between protein particles. To illustrate the thermodynamic framework, one parameter each is fitted to experimental precipitation data for aqueous saline one-protein systems containing either lysozyme or ovalbumin. A lysozyme–ovalbumin interaction parameter is then introduced to calculate phase behavior in the aqueous two-protein system. These calculations are remarkably similar to classic vapor–liquid equilibrium calculations using an equation of state. For the aqueous two-protein system, calculations give the light-phase composition as well as the lysozyme and ovalbumin partition coefficients for a given dense-phase composition. Agreement with sparse experimental data is reasonable over a range of pH and high ionic strength provided by the common precipitant ammonium sulfate. 相似文献