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91.
JB Thomas MJ Fall JB Cooper RB Rothman SW Mascarella H Xu JS Partilla CM Dersch KB McCullough BE Cantrell DM Zimmerman FI Carroll 《Canadian Metallurgical Quarterly》1998,41(26):5188-5197
A three-component library of compounds was prepared in parallel using multiple simultaneous solution-phase synthetic methodology. The compounds were biased toward opioid receptor antagonist activity by incorporating (+)-(3R,4R)-dimethyl-4-(3-hydroxyphenyl)piperidine (a potent, nonselective opioid pure antagonist) as one of the monomers. The other two monomers, which included N-substituted or unsubstituted Boc-protected amino acids and a range of substituted aryl carboxylic acids, were selected to add chemical diversity. Screening of these compounds in competitive binding experiments with the kappa opioid receptor selective ligand [3H]U69,593 led to the discovery of a novel kappa opioid receptor selective ligand, N-?(2'S)-[3-(4-hydroxyphenyl)propanamido]-3'-methylbutyl?-(3R, 4R)-dimethyl-4-(3-hydroxyphenyl)piperidine (8, RTI-5989-29). Additional structure-activity relationship studies suggested that 8 possesses lipophilic and hydrogen-bonding sites that are important to its opioid receptor potency and selectivity. These sites appear to exist predominantly within the kappa receptor since the selectivity arises from a 530-fold loss of affinity of 8 for the mu receptor and an 18-fold increase in affinity for the kappa receptor relative to the mu-selective ligand, (+)-N-[trans-4-phenyl-2-butenyl]-(3R, 4R)-dimethyl-4-(3-hydroxyphenyl)piperidine (5a). The degree of selectivity observed in the radioligand binding experiments was not observed in the functional assay. According to its ability to inhibit agonist stimulated binding of [35S]GTPgammaS at all three opioid receptors, compound 8 behaves as a mu/kappa opioid receptor pure antagonist with negligible affinity for the delta receptor. 相似文献
92.
In response to D. Cicchetti's (see record 1998-01884-002) and W. A. Mason's (see record 1998-01884-003) commentaries, this article scrutinizes infant maltreatment in monkeys and its public health implications. Studies of infant abuse and neglect in monkeys have used operational definitions based on (a) adult behavior or (b) adult behavior and infant outcome (depending on data available for analysis). Direct comparisons between the incidence of maltreatment in monkey and human populations can be only tentative as a result of differences in operational definitions of maltreatment. A simplified version of the ecological-transactional model of maltreatment can be used in research with nonhuman primates, and different species can be used to model different aspects of the human phenomenon. Although abuse and neglect take different forms in animals and humans, research with animal models can make an important contribution to elucidating the adaptive function, if any, of child maltreatment and the proximate mechanisms underlying its occurrence. (PsycINFO Database Record (c) 2010 APA, all rights reserved) 相似文献
93.
Einstein Gilles O.; McDaniel Mark A.; Richardson Sarah L.; Guynn Melissa J.; Cunfer Allison R. 《Canadian Metallurgical Quarterly》1995,21(4):996
Past research has frequently failed to find age differences in prospective memory. This article tested the possibility that age differences would be more likely to emerge on a prospective memory task that was high in self-initiated retrieval. In the 1st experiment, participants were asked to perform an action every 10 min (a time-based task presumed to be high in self-initiated retrieval); in the 2nd experiment, participants were asked to perform an action whenever a particular word was presented (an event-based task presumed to be relatively low in self-initiated retrieval). Age differences were found with the time-based task but not with the event-based task. This pattern of age differences was again found in a 3rd experiment in which a new experimental procedure was used and the nature of the prospective memory task was directly varied. Generally, the results suggest that self-initiated retrieval processes are an important component of age-related differences across both retrospective and prospective memory tasks. (PsycINFO Database Record (c) 2010 APA, all rights reserved) 相似文献
94.
Clotilde LM Bernard C Sequera DE Karmali A Fusellier A Carter JM 《Journal of laboratory automation》2012,17(4):309-314
Conventional enzyme-linked immunosorbent assay (ELISA) is a gold standard for screening antibodies and testing for protein or antigen presence. A significant limitation of this assay resides in the fact that only one analyte can be assessed per microplate well. Here, we describe and investigate a new technology consisting of an automated ELISA system in which up to 10 analytes can be measured within one single well, thus improving productivity, accuracy, and repeatability by reducing the amount of human labor required. Another strength of the platform is that a user can load any necessary sets/subsets of beads to perform required assays, with improved flexibility compared to manufactured-loaded arrays for multiplex analysis. We also demonstrate that this system can be used to determine the pathogenicity (i.e., presence of Shiga toxins) and serotype (i.e., Escherichia coli O157) of E. coli isolates. 相似文献
95.
In the first section of the article, we examine some recent criticisms of the connectionist enterprise: first, that connectionist models are fundamentally behaviorist in nature (and, therefore, non-cognitive), and second that connectionist models are fundamentally associationist in nature (and, therefore, cognitively weak). We argue that, for a limited class of connectionist models (feed-forward, pattern-associator models), the first criticism is unavoidable. With respect to the second criticism, we propose that connectionist modelsare fundamentally associationist but that this is appropriate for building models of human cognition. However, we do accept the point that there are cognitive capacities for which any purely associative model cannot provide a satisfactory account. The implication that we draw from is this is not that associationist models and mechanisms should be scrapped, but rather that they should be enhanced.In the next section of the article, we identify a set of connectionist approaches which are characterized by active symbols — recurrent circuits which are the basis of knowledge representation. We claim that such approaches avoid criticisms of behaviorism and are, in principle, capable of supporting full cognition. In the final section of the article, we speculate at some length about what we believe would be the characteristics of a fully realized active symbol system. This includes both potential problems and possible solutions (for example, mechanisms needed to control activity in a complex recurrent network) as well as the promise of such systems (in particular, the emergence of knowledge structures which would constitute genuine internal models). 相似文献
96.
The affect of substrate roughness and coating thickness on the corrosion resistance of electroless nickel coatings on mild steel in a 0.99M Na2SO4 + 0.01 M H2SO4 + 0.05M NaCl solution has been investigated using electrochemical techniques. The coating was electrochemically more active than pure nickel. The anodic polarization, corrosion potential, and corrosion current depend on the substrate roughness and coating thickness. The substrate roughness decreased for finishes in the order, as-ground, 240 grit, 600 grit, and 1 m diamond polish, but the corrosion current on relatively thin coatings decreased in the order 240 grit, as-ground, 600 grit, and 1 m diamond finish. The corrosion potential and the corrosion current of coatings more than about 10m thick were independent of the surface roughness and similar to those observed with pure nickel. The fraction porosity was estimated to be about 0.005 in a coating about 5 m thick on a 600 SiC grit substrate. 相似文献
97.
A Gaussian sum filter (GSF) with component extended Kalman filters (EKF) is proposed as an approach to localizing an autonomous vehicle in an urban environment with limited GPS availability. The GSF uses vehicle‐relative vision‐based measurements of known map features coupled with inertial navigation solutions to accomplish localization in the absence of GPS. The vision‐based measurements have multimodal measurement likelihood functions that are well represented as weighted sums of Gaussian densities. The GSF is used because of its ability to represent the posterior distribution of the vehicle pose with better efficiency (fewer terms, less computational complexity) than a corresponding bootstrap particle filter with various numbers of particles because of the interaction with measurement hypothesis tests. The expectation‐maximization algorithm is used off line to determine the representational efficiency of the particle filter in terms of an effective number of Gaussian densities. In comparison, the GSF, which uses an iterative condensation procedure after each iteration of the filter to maintain real‐time capabilities, is shown through a series of in‐depth empirical studies to more accurately maintain a representation of the posterior distribution than the particle filter using 37 min of recorded data from Cornell University's autonomous vehicle driven in an urban environment, including a 32 min GPS blackout. © 2012 Wiley Periodicals, Inc. 相似文献
98.
The dynamic capacity theorem characterizes the reliable communication rates of a quantum channel when combined with the noiseless resources of classical communication, quantum communication, and entanglement. In prior work, we proved the converse part of this theorem by making contact with many previous results in the quantum Shannon theory literature. In this work, we prove the theorem with an ??ab initio?? approach, using only the most basic tools in the quantum information theorist??s toolkit: the Alicki-Fannes?? inequality, the chain rule for quantum mutual information, elementary properties of quantum entropy, and the quantum data processing inequality. The result is a simplified proof of the theorem that should be more accessible to those unfamiliar with the quantum Shannon theory literature. We also demonstrate that the ??quantum dynamic capacity formula?? characterizes the Pareto optimal trade-off surface for the full dynamic capacity region. Additivity of this formula reduces the computation of the trade-off surface to a tractable, textbook problem in Pareto trade-off analysis, and we prove that its additivity holds for the quantum Hadamard channels and the quantum erasure channel. We then determine exact expressions for and plot the dynamic capacity region of the quantum dephasing channel, an example from the Hadamard class, and the quantum erasure channel. 相似文献
99.
A rapidly solidified (Co, Fe)3O4 spinel was formed in a cobalt-iron-phosphate glass matrix by gas atomization of melts of composition 37.5% mol % CoO, 37.5%Fe2O3, 25% P2O5; and 40% CoO, 40% Fe2O3, 20% P2O5, and the material has been characterized using size analysis, X-ray diffraction, Mössbauer spectroscopy, and scanning electron microscopy with energy dispersive X-ray spectroscopy.In the 20 mol % P2O5 composition, atomized powder 50–100m in diameter contained 33 wt % (Co, Fe)3O4. The ferrite crystallized as randomly oriented, faceted dendrites parallel to 100, and the growth was apparently diffusion controlled. Unlike the ferrite, where iron is in both tetrahedral and octahedral coordination, the iron in the glassy matrix was predominantly in distorted octahedral coordination. Overall particle size distributions were broad (15–700m), with 50 wt % smaller than 200m. The maximum in the size distribution shifted from 150 to 80m on increasing the atomizing pressure from 7 to 20 bar (100 to 300 psi). Calculations have shown that the cooling rates obtained with oxide melts vary strongly with droplet size, and less strongly with melt temperature. 相似文献
100.
Summary The desire to extend the applicability of the relational model beyond traditional data-processing applications has stimulated interest in nested or non-first normal form relations in which the attributes of a relation can take on values which are sets or even relations themselves. In this paper, we study the role of null values in the nested relational model using an open world assumption. We extend the traditional theory and study the properties of extended operators for nested relations containing nulls. The no-information, unknown, and non-existent interpretation of nulls are discussed and the meaning of empty set is clarified. Finally, contrary to several previous results, we determine that the traditional axiomatization of functional and multivalued dependencies is valid in the presence of nulls.Currently with the Air Force Institute of Technology, AFIT/ENG, Wright-Patterson AFB, OH 45433, USAResearch partially supported by an IBM Faculty Development A ward and NSF grant DCR-8507224 相似文献