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排序方式: 共有94条查询结果,搜索用时 15 毫秒
1.
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
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The DTN architecture is based around sender-initiated unicast communication that is insufficient or inconvenient to meet the needs of many applications. To address these limitations, we define a DTN session layer and associated extensions to the DTN bundle protocol that more naturally support receiver-driven applications and multicast communication. Within a session, we provide mechanisms allowing applications to convey ordering relationships between successive transmissions that can be used by the network to help ensure a distributed application’s delivery ordering expectations are met. We also extend the bundle protocol’s expiration procedures to support more efficient network utilization by allowing in-network deletion of obsolete messages. We present the design rationale and describe our implementation of these mechanisms and discuss their advantages in meeting the needs of several popular types of applications. 相似文献
4.
The case for technology in developing regions 总被引:1,自引:0,他引:1
Brewer E. Demmer M. Du B. Ho M. Kam M. Nedevschi S. Pal J. Patra R. Surana S. Fall K. 《Computer》2005,38(6):25-38
Alongside good governance, technology is considered among the greatest enablers for improved quality of life. However, the majority of its benefits have been concentrated in industrialized nations and therefore limited to a fraction of the world's population. We believe that technology has a large role to play in developing regions, that "First World" technology to date has been a poor fit in these areas, and that there is thus a need for technology research for developing regions. Despite the relative infancy of technology studies in developing regions, anecdotal evidence suggests that access to technology has a beneficial economic impact. Cellular telephony is probably the most visible application, but there are many others, some of which we cover in this article. The World Bank's infoDev site catalogs hundreds of information and communications technologies (ICT) projects, albeit not all successful. Most of these projects use existing off-the-shelf technology designed for the industrialized world. Although it is clear that there are large differences in assumptions related to cost, power, and usage, there has been little work on how technology needs in developing regions differ from those of industrialized nations. We argue that Western market forces continue to meet the needs of developing regions accidentally at best. 相似文献
5.
Fall BI Eberlein-König B Behrendt H Niessner R Ring J Weller MG 《Analytical chemistry》2003,75(3):556-562
The described in vitro test system for allergy diagnosis is based on microscope glass slides activated with (3-glycidyloxypropyl)trimethoxysilane. Allergen solutions are immobilized as small droplets (approximately 10 nL) on the activated glass slides with a piezoelectric arrayer. In contrast to other tests for specific IgE, such as Pharmacia CAP FEIA, AlaSTAT, or FAST, only a 25-microL serum sample is needed for the screening of allergen-specific IgE against a multitude of allergens and the test can be performed in less than 1 h. Compared with multiallergen dipstick screening tests (e.g., IgEquick, CMG Immunodot) based on multiallergen-coated nitrocellulose strips, the measurement of the microarray-based system can be performed automatically. The chemiluminescence intensities are detected with a sensitive CCD camera. Allergen extracts and recombinant/purified allergens (24 preparations) have been used on the same modified surface for the screening of allergen-specific IgE. With these disposable microarray slides, it is possible to distinguish between patients with and without elevated levels of allergen-specific IgE. Repeated measurements of serum samples demonstrated a sufficient reproducibility. Detection limits (microg/L) of 0.35 (r Betvl), 0.16 (PLA2), and 1.9 (Der p1) were achieved. 相似文献
6.
J Taucher A Hansel A Jordan R Fall JH Futrell W Lindinger 《Canadian Metallurgical Quarterly》1997,11(11):1230-1234
A new analytical method using proton-transfer-reaction mass spectrometry (PTRMS) is described for the determination of trace constituents in human breath. PTRMS is sufficiently sensitive and specific that it does not require preconcentration or separation. At its present stage of development it is capable of detecting trace constituents present in air at the part-per-billion level. These capabilities are illustrated for isoprene, one of the most abundant endogenous hydrocarbons. Our results confirm recent observations of a diurnal level variation associated with sleep or wakefulness; a new finding is that young children have much lower levels of isoprene in breath than adults. To address the metabolic origin of human isoprene, we used PTRMS to analyze expired air for allylic C5 alcohols that have been proposed to be non-enzymatic precursors of isoprene. The lack of correlation between peak breath isoprene and these alcohols suggests that the hydrocarbon is formed by some other mechanism. 相似文献
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8.
SM Gueye M Ba C Sylla AK Ndoye PA Fall JJ Diaw A Mensah 《Canadian Metallurgical Quarterly》1998,8(2):240-243
We report the case of a 33-year-old man with a severe Crohn's disease since the age of sixteen. He presented with acne and palmoplantar pustulosis associated with a right knee synovitis. Investigations revealed a major axial bone condensation. The association synovitis-acne-pustulosis-hyperostosis-osteitis leaded to the diagnosis of SAPHO syndrome associated with Crohn's disease. 相似文献
9.
ND Dore PN LeSou?f B Masters PW Francis DM Cooper JH Wildhaber AJ Fall PD Sly 《Canadian Metallurgical Quarterly》1998,26(6):380-388
Atypical mycobacterial infection in HIV-negative children usually presents with cervical lymphadenopathy. We report on 10 children who are HIV-negative and who presented with pulmonary disease, in whom either culture-proven atypical mycobacterium infection (four), positive avian Mantoux test (five), or lack of response to human tuberculosis treatment (one) had been observed. One case was subsequently diagnosed as chronic granulomatous disease and illustrates that children with atypical mycobacterial pulmonary infection should have their immune status fully investigated. Bronchial obstruction was observed in eight cases, and of these, endobronchial disease was found in six children. The diagnosis of atypical mycobacterial disease is difficult, and a negative avian Mantoux test does not exclude the diagnosis. The availability of clarithromycin and rifabutin has offered new therapeutic options in treating atypical mycobacterial pulmonary infection, but management of these cases can be prolonged and difficult. 相似文献
10.
The purpose of the study was evaluate hepatic (portal and arterial) and splenic perfusion at parenchymal level using dynamic computed tomography (CT) in patients with diffuse liver disease and controls. Nineteen patients and 30 normal controls underwent dynamic CT of the liver. Single-location dynamic sequences were carried out after intravenous administration of a 40 ml bolus of contrast medium (Ioversol: 5 cc/s). Hepatic arterial perfusion, hepatic portal perfusion and splenic perfusion were calculated from time-attenuation curves. Hepatic portal perfusion was significantly lower in patients (0.63 +/- 0.33 ml/min/ml (mean +/- SD); P = 0.003) compared with that in controls (1.03 +/- 0.43), although hepatic arterial perfusion did not differ (0.090 +/- 0.044 versus 0.102 +/- 0.114). Splenic arterial perfusion was significantly lower in patients (0.92 +/- 0.31; P = 0.0009) than in controls (1.35 +/- 0.44). The decreased hepatic portal perfusion in patients with diffuse liver disease was not supplemented by an increase in hepatic arterial perfusion. The decreased splenic perfusion in patients may be due to increased portal pressure. Dynamic CT enables quantification of hepatic and splenic perfusion. 相似文献