301 research outputs found

    Availability Analysis of Redundant and Replicated Cloud Services with Bayesian Networks

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    Due to the growing complexity of modern data centers, failures are not uncommon any more. Therefore, fault tolerance mechanisms play a vital role in fulfilling the availability requirements. Multiple availability models have been proposed to assess compute systems, among which Bayesian network models have gained popularity in industry and research due to its powerful modeling formalism. In particular, this work focuses on assessing the availability of redundant and replicated cloud computing services with Bayesian networks. So far, research on availability has only focused on modeling either infrastructure or communication failures in Bayesian networks, but have not considered both simultaneously. This work addresses practical modeling challenges of assessing the availability of large-scale redundant and replicated services with Bayesian networks, including cascading and common-cause failures from the surrounding infrastructure and communication network. In order to ease the modeling task, this paper introduces a high-level modeling formalism to build such a Bayesian network automatically. Performance evaluations demonstrate the feasibility of the presented Bayesian network approach to assess the availability of large-scale redundant and replicated services. This model is not only applicable in the domain of cloud computing it can also be applied for general cases of local and geo-distributed systems.Comment: 16 pages, 12 figures, journa

    Phosphocholine – an agonist of metabotropic but not of ionotropic functions of alpha9-containing nicotinic acetylcholine receptors

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    We demonstrated previously that phosphocholine and phosphocholine-modified macromolecules efficiently inhibit ATP-dependent release of interleukin-1beta from human and murine monocytes by a mechanism involving nicotinic acetylcholine receptors (nAChR). Interleukin-1beta is a potent pro-inflammatory cytokine of innate immunity that plays pivotal roles in host defence. Control of interleukin-1beta release is vital as excessively high systemic levels cause life threatening inflammatory diseases. In spite of its structural similarity to acetylcholine, there are no other reports on interactions of phosphocholine with nAChR. In this study, we demonstrate that phosphocholine inhibits ion-channel function of ATP receptor P2X7 in monocytic cells via nAChR containing alpha9 and alpha10 subunits. In stark contrast to choline, phosphocholine does not evoke ion current responses in Xenopus laevis oocytes, which heterologously express functional homomeric nAChR composed of alpha9 subunits or heteromeric receptors containing alpha9 and alpha10 subunits. Preincubation of these oocytes with phosphocholine, however, attenuated choline-induced ion current changes, suggesting that phosphocholine may act as a silent agonist. We conclude that phophocholine activates immuno-modulatory nAChR expressed by monocytes but does not stimulate canonical ionotropic receptor functions

    Die Verzerrung von Erinnerungen durch das Vorwissen der Befragten: die Rolle impliziter Theorien

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    'Implizite Theorien sind schematische Wissenstrukturen über die Stabilität oder die Veränderbarkeit von Merkmalen (Ross 1989). Diese Theorien haben die Funktion, Gedächtnislücken zu füllen, wenn eine genaue Erinnerung nicht möglich ist. Wenn sie jedoch nicht mit der Realität übereinstimmen, führen implizite Theorien zu systematischen Erinnerungsverzerrungen. Es wurde davon ausgegangen, daß Patienten nach einer Operation einen monotonen Genesungsverlauf im Hinblick auf Schmerzen und Schlaf erwarten, und daß diese implizite Theorie die Erinnerung beeinflußt. Sechzig Patienten wurden an fünf aufeinanderfolgenden Tagen im Anschluß an eine orthopädische Operation nach ihren Schmerzen und dem Schlaf der letzten Nacht befragt: am fünften Tag sollten sie sich an ihre Antworten der vergangenen vier Tage erinnern. Es traten systematische Erinnerungsverzerrungen auf. Der Befindlichkeits zustand des ersten Tages wurde in der Erinnerung unterschätzt. In der Erinnerung gab es mehr monotone Verläufe als im täglichen Bericht, Rückfälle im Genesungsprozeß wurden systematisch vergessen. Korrekte implizite Theorien können aber auch zuverlässig Erinnerungslücken schließen. Personen mit monotonen Genesungsverläufen zeigten eine bessere Erinnerungsleistung als Personen, in deren Genesungsverlauf Rückfälle aufgetreten waren.' (Autorenreferat)'Implicit theories are defined as schematic structures of knowledge about the stability or change of characteristics (Ross 1989). These theories can be used to fill in gaps in recall when memory fails. However, if an implicit theory is incorrect, it may lead to a systematic bias in recall. We hypothesized that patients expect a linear improvement in pain and sleep after an operation so that this implicit theory influences subsequent recall of pain and sleep quality. Sixty surgical patients were asked to rate their pain intensity and sleep quality on each of the 5 days following their operation. On day 5 they were also asked to recall their previous ratings. The recall errors we observed were systematic: The recalled health status of the first post-operative day was worse than the actual reported status. Improvement was recalled more often monotonously than actually reported. Setbacks and relapses in recovery over the the 5-day period tended to be systematically forgotten. On the other hand, correct implicit theories can help to fill recall gaps. Our results suggest that patients whose condition improves linearly post-operatively recalled their ratings more accurately than patients with non-linear patterns of recovery.' (author's abstract)

    Inequality and Income Dynamics in Germany

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    We provide a comprehensive analysis of income inequality and income dynamics for Germany over the last two decades. Combining personal income tax and social security data allows us – for the first time – to offer a complete picture of the distribution of annual earnings in Germany. We find that cross-sectional inequality rose until 2009 for men and women. After the Great Recession inequality continued to rise at a slower rate for men and fell slightly for women due to compression at the lower tail. We further document substantial gender differences in average earnings and inequality over the life-cycle. While for men earnings rise and inequality falls as they grow older, many women reduce working hours when starting a family such that average earnings fall and inequality increases. Men’s earnings changes are on average smaller than women’s but are substantially more affected by the business cycle. During the Great Recession, men’s earnings losses become magnified and gains are attenuated. Apart from recession years, earnings changes are significantly right-skewed reflecting the good overall state of the German labor market and increasing labor supply. In the second part of the paper, we study the distribution of total income including incomes of self-employed, business owners, and landlords. We find that total inequality increased significantly more than earnings inequality. Regarding income dynamics, entrepreneurs’ income changes are more dispersed, less skewed, less leptokurtic and less dependent on average past income than workers’ income changes. Finally, we find that top income earners have become less likely to fall out of the top 1 and 0.1 percent

    TNF inhibits malaria hepatic stages in vitro via synthesis of IL-6

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    We examined the capacity of murine recombinant tumor necrosis factor (rmTNF) to induce an inhibitory effect at the hepatic stage on malaria induced by Plasmodium yoelll sporozoitea. When injected three times, 1.0 μg of rmTNF was found to protect 78% of mice against a sporozoite challenge. In contrast, whatever the dose and the schedule of administration, no inhibition was observed when purified hepatocyte cultures were infected with P. yoelii. The addition of non-parenchymal hepatic cells to hepatocyte cultures restored the capacity of TNF to modulate hepatic stage development, leading to up to 44% inhibition. Antibodies to interleukin 6 reversed the anti-parasite activity in the co-culture syste

    Thermal Transition Design and Beam Heat-load Estimation for the COLDDIAG Refurbishment

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    The COLDDIAG (cold vacuum chamber for beam heat load diagnostics) developed at Karlsruhe Institute of Technology has been modified for more studies at cryogenic temperatures different from the previous operations at 4 K in a cold bore and at 50 K in a thermal shield. The key components in this campaign are two thermal transitions connecting both ends of the bore at 50 K with the shield at the same or higher temperature. In this paper, we present design efforts for the compact transitions, allowed heat intakes to the cooling power margin and mechanical robustness in the cryogenic environment. A manufacture scheme for the transition and its peripheral is also given. In addition, the beam heat loads in the refurbished COLDDIAG are estimated in terms of the accelerator beam parameters

    Metabolic engineering of Halomonas elongata: Ectoine secretion is increased by demand and supply driven approaches

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    The application of naturally-derived biomolecules in everyday products, replacing conventional synthetic manufacturing, is an ever-increasing market. An example of this is the compatible solute ectoine, which is contained in a plethora of treatment formulations for medicinal products and cosmetics. As of today, ectoine is produced in a scale of tons each year by the natural producer Halomonas elongata. In this work, we explore two complementary approaches to obtain genetically improved producer strains for ectoine production. We explore the effect of increased precursor supply (oxaloacetate) on ectoine production, as well as an implementation of increased ectoine demand through the overexpression of a transporter. Both approaches were implemented on an already genetically modified ectoine-excreting strain H. elongata KB2.13 (ΔteaABC ΔdoeA) and both led to new strains with higher ectoine excretion. The supply driven approach led to a 45% increase in ectoine titers in two different strains. This increase was attributed to the removal of phosphoenolpyruvate carboxykinase (PEPCK), which allowed the conversion of 17.9% of the glucose substrate to ectoine. For the demand driven approach, we investigated the potential of the TeaBC transmembrane proteins from the ectoine-specific Tripartite ATP-Independent Periplasmic (TRAP) transporter as export channels to improve ectoine excretion. In the absence of the substrate-binding protein TeaA, an overexpression of both subunits TeaBC facilitated a three-fold increased excretion rate of ectoine. Individually, the large subunit TeaC showed an approximately five times higher extracellular ectoine concentration per dry weight compared to TeaBC shortly after its expression was induced. However, the detrimental effect on growth and ectoine titer at the end of the process hints toward a negative impact of TeaC overexpression on membrane integrity and possibly leads to cell lysis. By using either strategy, the ectoine synthesis and excretion in H. elongata could be boosted drastically. The inherent complementary nature of these approaches point at a coordinated implementation of both as a promising strategy for future projects in Metabolic Engineering. Moreover, a wide variation of intracelllular ectoine levels was observed between the strains, which points at a major disruption of mechanisms responsible for ectoine regulation in strain KB2.13.This work has been funded by the German Federal Ministry of Education and Research (BMBF) through project HOBBIT (031B03)

    Networking: Theoretical foundations and construct validity

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    Wolff H-G, Moser K, Grau A. Networking: Theoretical foundations and construct validity. In: Deller J, ed. Readings in applied organizational behavior from the Lüneburg symposium - Personality at work. Mering: Rainer Hampp; 2008: 101-118

    Adaptation to Varying Salinity in Halomonas elongata: Much More Than Ectoine Accumulation

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    The halophilic γ-proteobacterium Halomonas elongata DSM 2581 T thrives at salt concentrations well above 10 % NaCl (1.7 M NaCl). A well-known osmoregulatory mechanism is the accumulation of the compatible solute ectoine within the cell in response to osmotic stress. While ectoine accumulation is central to osmoregulation and promotes resistance to high salinity in halophilic bacteria, ectoine has this effect only to a much lesser extent in non-halophiles. We carried out transcriptome analysis of H. elongata grown on two different carbon sources (acetate or glucose), and low (0.17 M NaCl), medium (1 M), and high salinity (2 M) to identify additional mechanisms for adaptation to high saline environments. To avoid a methodological bias, the transcripts were evaluated by applying two methods, DESeq2 and Transcripts Per Million (TPM). The differentially transcribed genes in response to the available carbon sources and salt stress were then compared to the transcriptome profile of Chromohalobacter salexigens, a closely related moderate halophilic bacterium. Transcriptome profiling supports the notion that glucose is degraded via the cytoplasmic Entner-Doudoroff pathway, whereas the Embden-Meyerhoff-Parnas pathway is employed for gluconeogenesis. The machinery of oxidative phosphorylation in H. elongata and C. salexigens differs greatly from that of non-halophilic organisms, and electron flow can occur from quinone to oxygen along four alternative routes. Two of these pathways via cytochrome bo' and cytochrome bd quinol oxidases seem to be upregulated in salt stressed cells. Among the most highly regulated genes in H. elongata and C. salexigens are those encoding chemotaxis and motility proteins, with genes for chemotaxis and flagellar assembly severely downregulated at low salt concentrations. We also compared transcripts at low and high-salt stress (low growth rate) with transcripts at optimal salt concentration and found that the majority of regulated genes were down-regulated in stressed cells, including many genes involved in carbohydrate metabolism, while ribosome synthesis was up-regulated, which is in contrast to what is known from non-halophiles at slow growth. Finally, comparing the acidity of the cytoplasmic proteomes of non-halophiles, extreme halophiles and moderate halophiles suggests adaptation to an increased cytoplasmic ion concentration of H. elongata. Taken together, these results lead us to propose a model for salt tolerance in H. elongata where ion accumulation plays a greater role in salt tolerance than previously assumed
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