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We present a new approach on how to provide institution-based semantics for UML state machines. Rather than capturing UML state machines directly as an institution, we build up a new logical framework \(\mathcal {M}^{\downarrow }_{\mathcal {D}}\) into which UML state machines can be embedded. A theoroidal comorphism maps \(\mathcal {M}^{\downarrow }_{\mathcal {D}}\) into the \(\textsc {Casl}\) institution. This allows for symbolic reasoning on UML state machines. By utilising the heterogeneous toolset \(\textsc {HeTS}\) that supports \(\textsc {Casl}\), a broad range of verification tools, including the automatic theorem prover \(\textsc {Spass}\), can be combined in the analysis of a single state machine.

In order to handle the database load for web scale applications, the conventional wisdom is that a cluster of database servers and a caching layer are essential. In this work, we argue that modern main memory database systems are often fast enough to consolidate this complex architecture into a single server (plus an additional fail over system). To demonstrate this claim, we design the Monopedia Benchmark , a benchmark for web scale applications modeled after Wikipedia. Using this benchmark, we show that it is indeed possible to run the database workload of one of the largest web sites in the world on a single database server.

Studienziel ist die Evaluation kurz- und mittelfristiger Therapieeffekte auf psychische Symptombelastung und Lebensqualitat von Eltern und Kindern in einer stationaren Eltern-Kind Rehabilitationsbehandlung. 4 Wochen vor Aufnahme, zu Beginn und Ende der Rehabilitation sowie 3 Monate danach wurden psychische Belastung und Lebensqualitat von Eltern und Kindern untersucht. Die Analysen basieren auf Daten von 256 Eltern, 397 Fremdbeurteilungen der Kinder durch die Eltern sowie 124 Selbstbeurteilungen der alteren Kinder. Im Vergleich zur Wartezeit vor Aufnahme zeigten sich bei Eltern und Kindern Verbesserungen bezuglich psychischer Symptombelastung und Lebensqualitat. Die Effekte persistieren grostenteils uber den Katamnesezeitraum. Stationare Eltern-Kind Rehabilitationsaufenthalte konnen als wirkungsvolle Masnahmen zur Verbesserung des psychischen Wohlbefindens und der Lebensqualitat von Eltern und Kindern angesehen werden.

Summary Proteasome-bearing bacteria make use of a ubiquitin-like modification pathway to target proteins for proteasomal turnover. In a process termed pupylation, proteasomal substrates are covalently modified with the small protein Pup that serves as a degradation signal. Pup is attached to substrate proteins by action of PafA. Prior to its attachment, Pup needs to undergo deamidation at its C-terminal residue, converting glutamine to glutamate. This step is catalysed in vitro by Dop. In order to characterize Dop activity in vivo, we generated a dop deletion mutant in Mycobacterium smegmatis. In the Δdop strain, pupylation is severely impaired and the steady-state levels of two known proteasomal substrates are drastically increased. Pupylation can be re-established by complementing the mutant with either DopWt or a Pup variant carrying a glutamate at its ultimate C-terminal position (PupGGE). Our data show that Pup is deamidated by Dop in vivo and that likely Dop alone is responsible for this activity. Furthermore, we demonstrate that a putative N-terminal ATP-binding motif is crucial for catalysis, as a single point mutation (E10A) in this motif abolishes Dop activity both in vivo and in vitro.

The authors request the retraction of the publication “A β-lactamase based reporter system for ESX dependent protein translocation in mycobacteria” because the main conclusions of the publication are unreliable. The main finding from the publication was the development of an ESX (precisely ESX-3) dependent protein translocation reporter based on an ampicillin resistant phenotype. Subsequent investigations by the authors have demonstrated that the reporter construct “pIV-blaTEM”, which was supposed to express the “Bla-TEM-EsxG” fusion protein, was accidentally replaced with a vector expressing a fusion protein carrying a twin-arginine-transporter (tat) secretion signal (not referenced in the publication). Re-testing of a newly constructed “true” BlaTEM-EsxG reporter strain indicated that the vector pIV-blaTEM does not confer an ampicillin-resistance phenotype. The second ESX reporter construct (pVI-blaTEM) expressing BlaTEM-EsxB does confer an ampicillin-resistance phenotype, but this phenotype does not depend on a functional ESX-1 secretion system as demonstrated by characterization of a subsequently generated eccD1 (MSMEG_0068) deletion mutant expressing BlaTEM-EsxB.

Protein secretion is essential for all bacteria in order to interact with their environment. Mycobacterium tuberculosis depends on protein secretion to subvert host immune response mechanisms. Both the general secretion system (Sec) and the twin-arginine translocation system (Tat) are functional in mycobacteria. Furthermore, a novel type of protein translocation system named ESX has been identified. In the genome of M. tuberculosis five paralogous ESX regions (ESX-1 to ESX-5) have been found. Several components of the ESX translocation apparatus have been identified over the last ten years. The ESX regions are composed of a basic set of genes for the translocation machinery and the main substrate - a heterodimer. The best studied of these heterodimers is EsxA (ESAT-6)/EsxB (CFP-10), which has been shown to be exported by ESX-1. EsxA/B is heavily involved in virulence of M. tuberculosis. EsxG/H is exported by ESX-3 and seems to be involved in an essential iron-uptake mechanism in M. tuberculosis. These findings make ESX-3 components high profile drug targets. Until now, reporter systems for determination of ESX protein translocation have not been developed. In order to create such a reporter system, a truncated β-lactamase ('bla TEM-1) was fused to the N-terminus of EsxB, EsxG and EsxU, respectively. These constructs have then been tested in a β-lactamase (BlaS) deletion strain of Mycobacterium smegmatis. M. smegmatis ΔblaS is highly susceptible to ampicillin. An ampicillin resistant phenotype was conferred by translocation of Bla TEM-1-Esx fusion proteins into the periplasm. BlaTEM-1-Esx fusion proteins were not found in the culture filtrate suggesting that plasma membrane translocation and outer membrane translocation are two distinct steps in ESX secretion. Thus we have developed a powerful tool to dissect the molecular mechanisms of ESX dependent protein translocation and to screen for novel components of the ESX systems on a large scale.

To evaluate the short- and medium-term effectiveness of an inpatient parent-child rehabilitation program in reducing symptoms of psychological distress and in increasing the quality of life of parents and children.Psychological problems and quality of life of parents and children were assessed 4 weeks before admission, at admission and discharge from the program, and 3 months post discharge using standardized questionnaires. The sample consisted of 256 parents, parent ratings of 397 children and self reports of 124 school-aged children.Compared to the waiting period prior to admission significant decreases in psychological problems as well as improvements in quality of life were found for both, parents and children. These effects proved to be stable over the follow-up period.Inpatient parent-child rehabilitation programs are effective in improving the psychological well-being and quality of life of parents and children.