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1.
We have characterized the compartment from which synaptic-like microvesicles (SLMVs), the neuroendocrine counterpart of neuronal synaptic vesicles, originate. For this purpose we have exploited the previous observation that newly synthesized synaptophysin, a membrane marker of synaptic vesicles and SLMVs, is delivered to the latter organelles via the plasma membrane and an internal compartment. Specifically, synaptophysin was labeled by cell surface biotinylation of unstimulated PC12 cells at 18 degrees C, a condition which blocked the appearance of biotinylated synaptophysin in SLMVs and in which there appeared to be no significant exocytosis of SLMVs. The majority of synaptophysin labeled at 18 degrees C with the membrane-impermeant, cleavable sulfo-NHS-SS-biotin was still accessible to extracellularly added MesNa, a 150-D membrane-impermeant thiol-reducing agent, but not to the 68,000-D protein avidin. The SLMVs generated upon reversal of the temperature to 37 degrees C originated exclusively from the membranes containing the MesNa-accessible rather than the MesNa-protected population of synaptophysin molecules. Biogenesis of SLMVs from MesNa-accessible membranes was also observed after a short (2 min) biotinylation of synaptophysin at 37 degrees C followed by chase. In contrast to synaptophysin, transferrin receptor biotinylated at 18 degrees or 37 degrees C became rapidly inaccessible to MesNa. Immunofluorescence and immunogold electron microscopy of PC12 cells revealed, in addition to the previously described perinuclear endosome in which synaptophysin and transferrin receptor are colocalized, a sub-plasmalemmal tubulocisternal membrane system distinct from caveolin-positive caveolae that contained synaptophysin but little, if any, transferrin receptor. The latter synaptophysin was selectively visualized upon digitonin permeabilization and quantitatively extracted, despite paraformaldehyde fixation, by Triton X-100. Synaptophysin biotinylated at 18 degrees C was present in these subplasmalemmal membranes. We conclude that SLMVs originate from a novel compartment that is connected to the plasma membrane via a narrow membrane continuity and lacks transferrin receptor. 相似文献
2.
Schmidt Frank L.; Law Kenneth; Hunter John E.; Rothstein Hannah R.; Pearlman Kenneth; McDaniel Michael 《Canadian Metallurgical Quarterly》1993,78(1):3
Using a large database, this study examined 3 refinements of validity generalization procedures: (1) a more accurate procedure for correcting the residual standard deviation (SD) for range restriction to estimate SDp, (2) use of r? instead of study-observed rs in the formula for sampling error variance, and (3) removal of non-Pearson rs. The 1st procedure does not affect the amount of variance accounted for by artifacts. The addition of the 2nd and 3rd procedures increased the mean percentage of validity variance accounted for by artifacts from 70 to 82%, a 17% increase. The cumulative addition of all 3 procedures decreased the mean SDp estimate from .150 to .106, a 29% decrease. Six additional variance-producing artifacts were identified that could not be corrected for. In light of these it was concluded that the obtained estimates of mean SDp and mean validity variance accounted for were consistent with the hypothesis that the true mean SDp value is close to zero. These findings provide further evidence against the situational specificity hypothesis. (PsycINFO Database Record (c) 2010 APA, all rights reserved) 相似文献
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Button Cathryn M.; Grant Malcolm J.; Hannah T. Edward; Ross Abraham S. 《Canadian Metallurgical Quarterly》1993,25(2):230
Two studies identified and labeled the dimensions that people use to judge others' attitudes. In the 1st study, 50 male and 50 female undergraduates viewed pairs of attitude statements drawn from 1 or 2 large sets. For each pair of statements, Ss judged whether or not a person who agreed with one statement in the pair would be likely to agree with the other. The dimensions of liberalism and traditional values were found to underlie perceived attitudes. Validity was confirmed in a 2nd study with 60 male and 60 female undergraduates who rated the characteristics of hypothetical people who agreed strongly with particular statements. Results suggest that there is a common structure to people's perceptions of others' attitudes. (French abstract) (PsycINFO Database Record (c) 2010 APA, all rights reserved) 相似文献
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Gathercole Susan E.; Pickering Susan J.; Ambridge Benjamin; Wearing Hannah 《Canadian Metallurgical Quarterly》2004,40(2):177
The structure of working memory and its development across the childhood years were investigated in children 4-15 years of age. The children were given multiple assessments of each component of the A. D. Baddeley and G. Hitch (1974) working memory model. Broadly similar linear functions characterized performance on all measures as a function of age. From 6 years onward, a model consisting of 3 distinct but correlated factors corresponding to the working memory model provided a good fit to the data. The results indicate that the basic modular structure of working memory is present from 6 years of age and possibly earlier, with each component undergoing sizable expansion in functional capacity throughout the early and middle school years to adolescence. (PsycINFO Database Record (c) 2010 APA, all rights reserved) 相似文献
8.
Dr. Armin Welker Dr. Christian Kersten Dr. Christin Müller Dr. Ramakanth Madhugiri Collin Zimmer Patrick Müller Robert Zimmermann Stefan Hammerschmidt Hannah Maus Prof. John Ziebuhr Prof. Christoph Sotriffer Prof. Tanja Schirmeister 《ChemMedChem》2021,16(2):340-354
Inhibition of coronavirus (CoV)-encoded papain-like cysteine proteases (PLpro) represents an attractive strategy to treat infections by these important human pathogens. Herein we report on structure-activity relationships (SAR) of the noncovalent active-site directed inhibitor (R)-5-amino-2-methyl-N-(1-(naphthalen-1-yl)ethyl) benzamide ( 2 b ), which is known to bind into the S3 and S4 pockets of the SARS-CoV PLpro. Moreover, we report the discovery of isoindolines as a new class of potent PLpro inhibitors. The studies also provide a deeper understanding of the binding modes of this inhibitor class. Importantly, the inhibitors were also confirmed to inhibit SARS-CoV-2 replication in cell culture suggesting that, due to the high structural similarities of the target proteases, inhibitors identified against SARS-CoV PLpro are valuable starting points for the development of new pan-coronaviral inhibitors. 相似文献
9.
Adam Bates Benjamin Mood Joe Pletcher Hannah Pruse Masoud Valafar Kevin Butler 《International Journal of Information Security》2014,13(2):171-189
Virtualization is the cornerstone of the developing third-party compute industry, allowing cloud providers to instantiate multiple virtual machines (VMs) on a single set of physical resources. Customers utilize cloud resources alongside unknown and untrusted parties, creating the co-resident threat—unless perfect isolation is provided by the virtual hypervisor, there exists the possibility for unauthorized access to sensitive customer information through the exploitation of covert side channels. This paper presents co-resident watermarking, a traffic analysis attack that allows a malicious co-resident VM to inject a watermark signature into the network flow of a target instance. This watermark can be used to exfiltrate and broadcast co-residency data from the physical machine, compromising isolation without reliance on internal side channels. As a result, our approach is difficult to defend against without costly underutilization of the physical machine. We evaluate co-resident watermarkingunder a large variety of conditions, system loads and hardware configurations, from a local laboratory environment to production cloud environments (Futuregrid and the University of Oregon’s ACISS). We demonstrate the ability to initiate a covert channel of 4 bits per second, and we can confirm co-residency with a target VM instance in $<$ 10 s. We also show that passive load measurement of the target and subsequent behavior profiling is possible with this attack. We go on to consider the detectability of co-resident watermarking, extending our scheme to create a subtler watermarking attack by imitating legitimate cloud customer behavior. Our investigation demonstrates the need for the careful design of hardware to be used in the cloud. 相似文献
10.
ABSTRACT Librarians at Oregon State University (OSU) Libraries used the discussion board features of Blackboard courseware to create an interactive experience for graduate students at a distance who could not attend the on-campus “Literature Review Workshops.” These recently developed workshops have been extremely popular with graduate students across the disciplines and have generated a growing demand from distance education graduate students and faculty to offer similar information online. Reluctant to simply deliver content via an online tutorial, librarians sought to duplicate the workshop atmosphere by making the sessions available for a short time-period online, asking participants to respond to discussion questions at specific points in the workshop, and offering audio-mediated online demonstrations of tools and resources. Student feedback and follow-up requests for more workshops support the perception that this approach offered a rewarding learning experience that addressed their specific adult learning needs. 相似文献