578 research outputs found

    The Effectiveness of Cache Coherence Implemented on the Web

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    The popularity of the World Wide Web (Web) has generated so much network traffic that it has increased concerns as to how the Internet will scale to meet future demand. The increased population of users and the large size of files being transmitted have resulted in concerns for different types of Internet users. Server administrators want a manageable load on their servers. Network administrators need to eliminate unnecessary traffic, thereby allowing more bandwidth for useful information. End users desire faster document retrieval. Proxy caches decrease the number of messages that enter the network by satisfying requests before they reach the server. However, the use of proxies introduces a concern with how to maintain consistency among cached document versions. Existing consistency protocols used in the Web are proving to be insufficient to meet the growing needs of the World Wide Web population. For example, too many messages are due to caches guessing when their copy is inconsistent. One option is to apply the cache coherence strategies already in use for many other distributed systems, such as parallel computers. However, these methods are not satisfactory for the World Wide Web due to its larger size and range of users. This paper provides insight into the characteristics of document popularity and how often these popular documents change. The frequency of proxy accesses to documents is also studied to test the feasibility of providing coherence at the server. The main goal is to determine whether server invalidation is the most effective protocol to use on the Web today. We make recommendations based on how frequently documents change and are accessed

    Insulin deficiency and reduced expression of lipogenic enzymes in cardiomyopathic hamster.

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    Evidence is given that the heart of the cardiomyopathic UM-X7.1 hamster has a lipid composition different from that of the same tissue isolated from animals of the Syrian hamster parent strain. Also, noncardiac tissues from cardiomyopathic and healthy hamsters exhibit significant compositional differences. On the basis of these preliminary observations, a comparative study of the hepatic biosynthesis of lipids in cardiomyopathic and healthy Syrian hamsters was undertaken. The results obtained indicate that the cardiomyopathic hamster is characterized by a generalized disturbance of lipid metabolism. In particular, the fatty acid synthase and stearoyl-CoA desaturase activities were significantly lower in the liver of UM-X7.1 hamsters than in age-matched healthy controls fed the same diet. Northern blot analysis of the mRNAs encoding the two enzymatic proteins and the "lipogenic" S14 nuclear protein indicated that the transcription of the respective genes was impaired in UM-X7.1.Short-term dietary manipulations modulated the expression of the above-mentioned genes both in cardiomyopathic and healthy animals. However, dietary carbohydrates were less effective in inducing the expression of lipogenic enzymes in UM-X7.1 liver than healthy controls. The main determinant of the metabolic defect pointed out in the present work appears to be represented by the low insulin level detectable in the plasma of the cardiomyopathic hamster.-Vecchini, A., L. Binaglia, M. Bibeau, M. Minieri, F. Carotenuto, and P. Di Nardo. Insulin deficiency and reduced expression of lipogenic enzymes in cardiomyopathic hamster. J. Lipid Res. 2001. 42: 96;-105

    Expression patterns in reductive iron assimilation and functional consequences during phagocytosis of lichtheimia corymbifera , an emerging cause of mucormycosis

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    Iron is an essential micronutrient for most organisms and fungi are no exception. Iron uptake by fungi is facilitated by receptor-mediated internalization of siderophores, heme and reductive iron assimilation (RIA). The RIA employs three protein groups: (i) the ferric reductases (Fre5 proteins), (ii) the multicopper ferroxidases (Fet3) and (iii) the high-affinity iron permeases (Ftr1). Phenotyping under different iron concentrations revealed detrimental effects on spore swelling and hyphal formation under iron depletion, but yeast-like morphology under iron excess. Since access to iron is limited during pathogenesis, pathogens are placed under stress due to nutrient limitations. To combat this, gene duplication and differential gene expression of key iron uptake genes are utilized to acquire iron against the deleterious effects of iron depletion. In the genome of the human pathogenic fungus L. corymbifera, three, four and three copies were identified for FRE5, FTR1 and FET3 genes, respectively. As in other fungi, FET3 and FTR1 are syntenic and co-expressed in L. corymbifera. Expression of FRE5, FTR1 and FET3 genes is highly up-regulated during iron limitation (Fe-), but lower during iron excess (Fe+). Fe- dependent upregulation of gene expression takes place in LcFRE5 II and III, LcFTR1 I and II, as well as LcFET3 I and II suggesting a functional role in pathogenesis. The syntenic LcFTR1 I–LcFET3 I gene pair is co-expressed during germination, whereas LcFTR1 IILcFET3 II is co-expressed during hyphal proliferation. LcFTR1 I, II and IV were overexpressed in Saccharomyces cerevisiae to represent high and moderate expression of intracellular transport of Fe3+, respectively. Challenge of macrophages with the yeast mutants revealed no obvious role for LcFTR1 I, but possible functions of LcFTR1 II and IVs in recognition by macrophages. RIA expression pattern was used for a new model of interaction between L. corymbifera and macrophages

    Data-driven modelling of the functional level in model-based systems engineering – Optimization of module scopes in modular development

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    The modelling of the functional level of technical systems can be supported by the analysis of machine usage data. By creating an understanding of the actual use of provided functions of offered machine configurations, the definition of module scopes in modular development can be optimized. Characteristics of specific machine usage can be assigned to physical elements using model-based systems engineering. Analyses on a purely functional system level can thus be placed in context with each other via the connection to physical elements. Consequently, critical elements in the system design can be systematically uncovered

    Structure of an Early Intermediate in the M-State Phase of the Bacteriorhodopsin Photocycle

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    AbstractThe structure of an early M-intermediate of the wild-type bacteriorhodopsin photocycle formed by actinic illumination at 230K has been determined by x-ray crystallography to a resolution of 2.0Å. Three-dimensional crystals were trapped by illuminating with actinic light at 230K, followed by quenching in liquid nitrogen. Amide I, amide II, and other infrared absorption bands, recorded from single bacteriorhodopsin crystals, confirm that the M-substate formed represents a structure that occurs early after deprotonation of the Schiff base. Rotation about the retinal C13—C14 double bond appears to be complete, but a relatively large torsion angle of 26° is still seen for the C14—C15 bond. The intramolecular stress associated with the isomerization of retinal and the subsequent deprotonation of the Schiff base generates numerous small but experimentally measurable structural changes within the protein. Many of the residues that are displaced during the formation of the late M (MN) substate formed by three-dimensional crystals of the D96N mutant (Luecke et al., 1999b) are positioned, in early M, between their resting-state locations and the ones which they will adopt at the end of the M phase. The relatively small magnitude of atomic displacements observed in this intermediate, and the well-defined positions adopted by nearly all of the atoms in the structure, may make the formation of this structure favorable to model (simulate) by molecular dynamics

    Postmortem Stability of SARS-CoV-2 in Nasopharyngeal Mucosa

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    Analyses of infection chains have demonstrated that severe acute respiratory syndrome coronavirus 2 is highly transmissive. However, data on postmortem stability and infectivity are lacking. Our finding of nasopharyngeal viral RNA stability in 79 corpses showed no time-dependent decrease. Maintained infectivity is supported by virus isolation up to 35 hours postmortem
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