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21.
We calculated the electrostatic force between a planar interface, such as a planar-supported lipid bilayer membrane, and the tip of a stylus on which another lipid bilayer or some other biomacromolecular system might be deposited. We considered styli with rounded tips as well as conical tips. To take into account the effect of dynamical hydrogen-bonded structures in the aqueous phase, we used a theory of nonlocal electrostatics. We used the Derjaguin approximation and identified the systems for which its use is valid. We pointed out where our approach differs from previous calculations and to what extent the latter are inadequate. We found that 1) the nonlocal interactions have significant effects over distances of 10-15 A from the polar zone and that, at the surface of this zone, the effect on the calculated force can be some orders of magnitude; 2) the lipid dipoles and charges are located a distance L from the hydrophobic layer in the aqueous medium and this can have consequences that may not be appreciated if it is ignored; 3) dipoles, located in the aqueous region, can give rise to forces even though the polar layer is unchanged, and if this is ignored the interpretation of force data can be erroneous if an attempt is made to rationalize an observed force with a knowledge of an uncharged surface; 4) the shape of the stylus tip can be very important, and a failure to take this into account can result in incorrect conclusions, a point made by other workers; and 5) when L is nonzero, the presence of charges and dipoles can yield a force that can be nonmonotonic as a function of ionic concentration.  相似文献   
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Peptides labelled with the fluorophore cyanine 3 were used to study naturally expressed neuropeptide receptors by confocal microscopy in continuous cell lines, primary cultures, and unfixed tissue. Swiss 3T3 fibroblasts bound cyanine 3-gastrin-releasing peptide at 4 degrees C, and internalized the peptide after 10 min at 37 degrees C. Internalization was specific, since it was blocked by incubation with unlabelled peptide. Primary cultures of myenteric neurons of the guinea pig incubated with cyanine 3-substance P at 4 degrees C had specific surface labelling. After 30 s at 37 degrees C, the peptide was internalized into vesicles in both the soma and neurites. Direct observation of live neurons showed movement of fluorescent vesicles to a perinuclear region after 30 min. Endocytosis was associated with a loss of surface binding sites. Unfixed whole mounts of guinea pig and rat ileum were incubated with cyanine 3-neurokinin A at 4 degrees C. After 5 min at 37 degrees C, Cy3-neurokinin A was specifically internalized in neurons and smooth muscle cells. After 30 min, a perinuclear labelling occurred in some cells. Labelling in rat neurons was diminished by the NK3-R antagonist SR142801. Thus, cyanine 3-neuropeptides are valuable tools to study expression and endocytosis of naturally expressed receptors.  相似文献   
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Staphylococcus aureus is a pathogen important in causing human infections and intoxication. A sensitive fiber-optic that produces evanescent waves was developed for the detection of protein A, a product secreted only by S. aureus. In the immunosensor, a 40-mV argon-ion laser that generated laser light at 488 nm was used together with plastic optical fiber and antibodies to protein A were physically adsorbed onto the fiber. The principle of the detection involved a sandwich immunoassay with fluorescein isothiocyanate conjugated with anti-(protein A) immunoglobulin G to produce signals of the antigen-antibody reaction. The detection limit was 1 ng of protein A per milliliter. The fiber-optic immunosensor could be used for rapid and specific detection of S. aureus in clinical specimens and foods.  相似文献   
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BACKGROUND: Simultaneous abuse of cocaine and alcohol is widespread and increasingly detected in patients seeking emergent care. This double-blind, randomized, within-subjects study used a paradigm more closely approximating practices of drug abusers to better understand the pathogenesis of cocaine-alcohol abuse. METHODS: Subjects meeting DSM-IV criteria for cocaine dependence and alcohol abuse participated in three drug administration sessions: four doses of intranasal cocaine (1 mg/kg every 30 min) with oral alcohol (1 g/kg) administered following the initial cocaine dose and a second dose (120 mg/kg) at 60 min calculated to maintain plasma alcohol concentration at approximately 100 mg/dL during cocaine administration; four doses of cocaine/placebo alcohol; four doses of cocaine placebo/alcohol. Pharmacokinetic, physiological, and behavioral effects were followed over 8 hours. RESULTS: Cocaine-alcohol produced greater euphoria and increased perception of well-being relative to cocaine. Heart rate significantly increased following cocaine-alcohol administration relative to either drug alone. Cocaine concentrations were greater following cocaine-alcohol administration. Cocaethylene had a longer halflife with increasing concentrations relative to cocaine at later time points. CONCLUSIONS: Enhanced psychological effects during cocaine-alcohol abuse may encourage ingestion of larger amounts of these substances over time placing users at heightened risk for greater toxicity than with either drug alone.  相似文献   
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Sick building syndrome is the term given to a heterogeneous constellation of symptoms that affects workers in modern mechanically ventilated office buildings. Although the cause is unknown, there is evidence that the local environment of the work station is an important determinant of symptoms. In this study, investigators examined the effect of a new, individually controlled ventilation system on workers' symptoms. Investigators studied two groups of workers in one mechanically ventilated office building: (1) a control group at whose worksite no intervention was made and (2) an intervention group. The intervention consisted of installation of a device that allowed each worker control over the ventilation supplied to his or her worksite. Just before, and 4 and 16 mo after installation of this device, workers completed self-administered questionnaires regarding occurrence of symptoms. The new ventilation system resulted in higher air velocities, more variable temperatures, and higher concentrations of airborne dust and fungal spores. Four months after installation, workers with the new ventilation system reported fewer symptoms that were (a) work-related (p < .05) and that were work-related and frequent (p < .05); in addition, they reported fewer symptoms that reduced their capacity to work (p < .01). Sixteen months after installation, workers with the new device reported fewer symptoms than at baseline (although not as significantly), and they indicated that the indoor air quality improved their productivity by 11%, compared with a 4% reduction of productivity among the control group of workers (p < .001). Investigators concluded that the new ventilation system, which provided the workers with individual control over ventilation, was associated with important and sustained reduction in symptoms.  相似文献   
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Health care providers and purchasers of health services have an opportunity to improve patient care and potentially save costs through the wise purchase of interactive health communication applications for patients and employees. Purchasing decisions based on evaluation and evidence should drive the design and development of new systems. The cycle of evaluation includes a needs assessment before system development, usability testing during development, and studies of use and outcomes in natural settings. This type of evidence is critical to our understanding of how best to provide health information and decision assistance to patients, employees, and others.  相似文献   
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