Atomic commitment in transactional DHTs

We investigate the problem of atomic commit in transactional database systems built on top of Distributed Hash Tables. DHTs provide a decentralized way to store and look up data. To solve the atomic commit problem we propose to use an adaption of Paxos commit as a non-blocking algorithm. We exploit the symmetric replication technique existing in the DKS DHT to determine which nodes are necessary to execute the commit algorithm. By doing so we achieve a lower number of communication rounds and a reduction of meta-data in contrast to traditional Three-Phase-Commit protocols. We also show how the proposed solution can cope with dynamism due to churn in DHTs. Our solution works correctly relying only on an inaccurate failure detection of node failure which is necessary for systems running over the Internet

„Für dich kein Einlass“ - Der kinorechtliche Jugendschutz in Österreich

Diese Diplomarbeit verfolgt das Ziel, auf die derzeitige rechtliche Situation des österreichischen kinorechtlichen Jugendschutzes und damit verbundenden problematische Regelungen aufmerk-sam zu machen. Nach der Darstellung der historischen gesetzlichen Entwicklung und Definitio-nen zu Begriffen von „Kind“ und „Jugendlicher“ erforscht diese Arbeit, basierend auf der Recher-che einschlägiger Fachliteratur und e-mail - basierten Anfragen an Experten, wie die österreichi-sche Rechtslage aufgebaut ist. Auffallend war dabei der noch immer vorherrschende Föderalis-mus, der dazu führt, dass dieses Rechtsgebiet nach wie vor äußerst unübersichtlich ist und so eine Akzeptanz derer, die diese Regeln befolgen müssen, fraglich ist. Mit der Jugendmedien-kommission beim Bundesministerium für Unterricht, Kunst und Kultur wurde immerhin eine Institution geschaffen, die fachlich kompetent Kinofilme prüft und eine Altersgrenze festsetzt, ab welcher ein Film im Kino von Kindern und Jugendlichen besucht werden darf. Diese an sich nicht verbindliche Altersfreigabe wird heute dennoch grundsätzlich von den meisten Bundesländern übernommen und schafft somit eine Quasi-Vereinheitlichung in der Freigabepraxis. Wesentlich für die Frage, ab wann welche Filme für welches Alter geeignet sind, ist dabei eine Frage der Medienwahrnehmung und der Entwicklung von Medienkompetenz. Anhand der Darlegung der verschiedenen Theorien in diesen Bereich wird klar, dass eine eindeutige Antwort auf diese Frage nicht möglich ist. Ausgehend vom Medienkompetenzmodell von Dieter Baacke ist die Individualität jedes Menschen zu berücksichtigen und sind zahlreiche andere Faktoren, wie Eltern, Bildungsanstalten oder „peer groups“, gefordert, die Entwicklung von Kindern und Jugendlichen entsprechend ihrer Bedürfnisse zu fördern. Die vorliegende Arbeit kam dabei zum Ergebnis, dass es bereits eine Vielzahl von Einrichtungen und politischen Bestrebungen gibt, die darauf abzielen, für die heutige Jugend ihrer Entwicklung entsprechende Entwicklungsmöglichkeiten zu bieten. Nach einem kurzen Überblick über die Bewertungspraxis anderer europäischer Länder kritisiert die vorliegende Arbeit die bestehenden jugendschutzrechtlichen Regelungen. Dies vor allem im Hinblick darauf, dass es immer wieder Vorstöße einzelner Politiker und Bewegungen gibt, die sich für eine Vereinheitlichung des österreichischen Jugendschutzes aussprechen, jedoch immer wieder an den Interessen einzelner Länder scheitern. Vermisst wird die Einrichtung einer verbindlichen Bewertungskommission und Vereinheitlichung der Rechtslage, um in diesem so wichigen Bereich Rechtssicherheit für Kinder und Jugendliche bieten zu können

Effects of Home Care on patients with hepatocellular carcinoma treated with sorafenib.

Background and Aim Treatment with sorafenib causes diverse side effects, which limits adherence. This work assesses whether Home Care, a psychosocial nursing intervention, prolongs the duration of treatment in patients with advanced hepatocellular carcinoma (HCC) and if it influences health-related quality of life (HRQL). Methods and Results This is a cohort study using data from patients receiving sorafenib in the prospective Bern HCC Cohort at the University Hospital. Duration of treatment, overall survival, and HRQL using the Functional Assessment of Cancer Therapy-Hepatobiliary questionnaire were compared in the two groups. A total of 173 patients were eligible for the analysis. Among them, 141 were in the Home Care program, and 32 were not. Patients with Home Care had a significantly longer duration of treatment (265 days vs 152 days, P = 0.003) and a better functional well-being (17.7 vs 12.5, P = 0.015). Conclusion Psychosocial interventions such as Home Care are a valid method in improving adherence to sorafenib and can therefore be recommended

Beurteilung von Musik. Gibt es Unterschiede zwischen Musikexperten und Laien?

Der Einfluß der musikalischen Vorbildung auf die Musikbeurteilung wird von den Autorinnen näher betrachten. Gibt es Unterschiede in den persönlichen Musikpräferenzen von Musikexperten und Laien? Wie unterscheidet sich ihre Beurteilung von konkreten Musikbeispielen? Ziehen Experten und Laien unterschiedliche Gesichtspunkte heran, um ihre persönliche Musik zu charakterisieren? (DIPF/Orig.

The transformer2 gene in Musca domestica is required for selecting and maintaining the female pathway of development

We present the isolation and functional analysis of a transformer2 homologue Mdtra2 in the housefly Musca domestica. Compromising the activity of this gene by injecting dsRNA into embryos causes complete sex reversal of genotypically female individuals into fertile males, revealing an essential function of Mdtra2 in female development of the housefly. Mdtra2 is required for female-specific splicing of Musca doublesex (Mddsx) which structurally and functionally corresponds to Drosophila dsx, the bottom-most regulator in the sex-determining pathway. Since Mdtra2 is expressed in males and females, we propose that Mdtra2 serves as an essential co-factor of F, the key sex-determining switch upstream of Mddsx. We also provide evidence that Mdtra2 acts upstream as a positive regulator of F supporting genetic data which suggest that F relies on an autocatalytic activity to select and maintain the female path of development. We further show that repression of male courtship behavior by F requires Mdtra2. This function of F and Mdtra2 appears not to be mediated by Mddsx, suggesting that bifurcation of the pathway at this level is a conserved feature in the genetic architecture of Musca and Drosophil

Bromodomain Protein Inhibitors Reorganize the Chromatin of Synovial Fibroblasts

Bromodomain- and extra-terminal domain (BET) proteins are epigenetic reader proteins that regulate transcription of their target genes by binding to acetylated histone side chains. Small molecule inhibitors, such as I-BET151, have anti-inflammatory properties in fibroblast-like synoviocytes (FLS) and in animal models of arthritis. Here, we investigated whether BET inhibition can also affect the levels of histone modifications, a novel mechanism underlying BET protein inhibition. On the one hand, FLSs were treated with I-BET151 (1 µM) for 24 h in absence and presence of TNF. On the other hand, FLSs were washed with PBS after 48 h of I-BET151 treatment, and the effects were measured 5 days after I-BET151 treatment or after an additional 24 h stimulation with TNF (5 d + 24 h). Mass spectrometry analysis indicated that I-BET151 induced profound changes in histone modifications, with a global reduction in acetylation on different histone side chains 5 days after treatment. We confirmed changes on acetylated histone side chains in independent samples by Western blotting. I-BET151 treatment reduced mean TNF-induced levels of total acetylated histone 3 (acH3), H3K18ac, and H3K27ac. In line with these changes, the TNF-induced expression of BET protein target genes was suppressed 5 d after I-BET151 treatment. Our data indicate that BET inhibitors not only prevent the reading of acetylated histones but directly influence overall chromatin organization, in particular after stimulation with TNF

Bromodomain Protein Inhibitors Reorganize the Chromatin of Synovial Fibroblasts.

Bromodomain- and extra-terminal domain (BET) proteins are epigenetic reader proteins that regulate transcription of their target genes by binding to acetylated histone side chains. Small molecule inhibitors, such as I-BET151, have anti-inflammatory properties in fibroblast-like synoviocytes (FLS) and in animal models of arthritis. Here, we investigated whether BET inhibition can also affect the levels of histone modifications, a novel mechanism underlying BET protein inhibition. On the one hand, FLSs were treated with I-BET151 (1 µM) for 24 h in absence and presence of TNF. On the other hand, FLSs were washed with PBS after 48 h of I-BET151 treatment, and the effects were measured 5 days after I-BET151 treatment or after an additional 24 h stimulation with TNF (5 d + 24 h). Mass spectrometry analysis indicated that I-BET151 induced profound changes in histone modifications, with a global reduction in acetylation on different histone side chains 5 days after treatment. We confirmed changes on acetylated histone side chains in independent samples by Western blotting. I-BET151 treatment reduced mean TNF-induced levels of total acetylated histone 3 (acH3), H3K18ac, and H3K27ac. In line with these changes, the TNF-induced expression of BET protein target genes was suppressed 5 d after I-BET151 treatment. Our data indicate that BET inhibitors not only prevent the reading of acetylated histones but directly influence overall chromatin organization, in particular after stimulation with TNF

The histone acetyl transferases CBP and p300 regulate stress response pathways in synovial fibroblasts at transcriptional and functional levels

The activation of stress response pathways in synovial fibroblasts (SF) is a hallmark of rheumatoid arthritis (RA). CBP and p300 are two highly homologous histone acetyl transferases and writers of activating histone 3 lysine 27 acetylation (H3K27ac) marks. Furthermore, they serve as co-factors for transcription factors and acetylate many non-histone proteins. Here we showed that p300 but not CBP protein expression was down regulated by TNF and 4-hydroxynonenal, two factors that mimic inflammation and oxidative stress in the synovial microenvironment. We used existing RNA-sequencing data sets as a basis for a further in-depth investigation of individual functions of CBP and p300 in regulating different stress response pathways in SF. Pathway enrichment analysis pointed to a profound role of CBP and/ or p300 in regulating stress response-related gene expression, with an enrichment of pathways associated with oxidative stress, hypoxia, autophagy and proteasome function. We silenced CBP or p300, and performed confirmatory experiments on transcriptome, protein and functional levels. We have identified some overlap of CBP and p300 target genes in the oxidative stress response pathway, however, with several genes being regulated in opposite directions. The majority of stress response genes was regulated by p300, with a specific function of p300 in regulating hypoxia response genes and genes encoding proteasome subunits. Silencing of p300 suppressed proteasome enzymatic activities. CBP and p300 regulated autophagy on transcriptome and functional levels. Whereas CBP was indispensable for autophagy synthesis, silencing of p300 affected late-stage autophagy. In line with impaired autophagy and proteasome function, poly-ubiquitinated proteins accumulated after silencing of p300

The histone acetyl transferases CBP and p300 regulate stress response pathways in synovial fibroblasts at transcriptional and functional levels.

The activation of stress response pathways in synovial fibroblasts (SF) is a hallmark of rheumatoid arthritis (RA). CBP and p300 are two highly homologous histone acetyl transferases and writers of activating histone 3 lysine 27 acetylation (H3K27ac) marks. Furthermore, they serve as co-factors for transcription factors and acetylate many non-histone proteins. Here we showed that p300 but not CBP protein expression was down regulated by TNF and 4-hydroxynonenal, two factors that mimic inflammation and oxidative stress in the synovial microenvironment. We used existing RNA-sequencing data sets as a basis for a further in-depth investigation of individual functions of CBP and p300 in regulating different stress response pathways in SF. Pathway enrichment analysis pointed to a profound role of CBP and/ or p300 in regulating stress response-related gene expression, with an enrichment of pathways associated with oxidative stress, hypoxia, autophagy and proteasome function. We silenced CBP or p300, and performed confirmatory experiments on transcriptome, protein and functional levels. We have identified some overlap of CBP and p300 target genes in the oxidative stress response pathway, however, with several genes being regulated in opposite directions. The majority of stress response genes was regulated by p300, with a specific function of p300 in regulating hypoxia response genes and genes encoding proteasome subunits. Silencing of p300 suppressed proteasome enzymatic activities. CBP and p300 regulated autophagy on transcriptome and functional levels. Whereas CBP was indispensable for autophagy synthesis, silencing of p300 affected late-stage autophagy. In line with impaired autophagy and proteasome function, poly-ubiquitinated proteins accumulated after silencing of p300

βIVΣ1 spectrin stabilizes the nodes of Ranvier and axon initial segments

Saltatory electric conduction requires clustered voltage-gated sodium channels (VGSCs) at axon initial segments (AIS) and nodes of Ranvier (NR). A dense membrane undercoat is present at these sites, which is thought to be key for the focal accumulation of channels. Here, we prove that βIVΣ1 spectrin, the only βIV spectrin with an actin-binding domain, is an essential component of this coat. Specifically, βIVΣ1 coexists with βIVΣ6 at both AIS and NR, being the predominant spectrin at AIS. Removal of βIVΣ1 alone causes the disappearance of the nodal coat, an increased diameter of the NR, and the presence of dilations filled with organelles. Moreover, in myelinated cochlear afferent fibers, VGSC and ankyrin G clusters appear fragmented. These ultrastructural changes can explain the motor and auditory neuropathies present in βIVΣ1 −/− mice and point to the βIVΣ1 spectrin isoform as a master-stabilizing factor of AIS/NR membranes