Biological diversity of prokaryotic type IV secretion systems.

Type IV secretion systems (T4SS) translocate DNA and protein substrates across prokaryotic cell envelopes generally by a mechanism requiring direct contact with a target cell. Three types of T4SS have been described: (i) conjugation systems, operationally defined as machines that translocate DNA substrates intercellularly by a contact-dependent process; (ii) effector translocator systems, functioning to deliver proteins or other macromolecules to eukaryotic target cells; and (iii) DNA release/uptake systems, which translocate DNA to or from the extracellular milieu. Studies of a few paradigmatic systems, notably the conjugation systems of plasmids F, R388, RP4, and pKM101 and the Agrobacterium tumefaciens VirB/VirD4 system, have supplied important insights into the structure, function, and mechanism of action of type IV secretion machines. Information on these systems is updated, with emphasis on recent exciting structural advances. An underappreciated feature of T4SS, most notably of the conjugation subfamily, is that they are widely distributed among many species of gram-negative and -positive bacteria, wall-less bacteria, and the Archaea. Conjugation-mediated lateral gene transfer has shaped the genomes of most if not all prokaryotes over evolutionary time and also contributed in the short term to the dissemination of antibiotic resistance and other virulence traits among medically important pathogens. How have these machines adapted to function across envelopes of distantly related microorganisms? A survey of T4SS functioning in phylogenetically diverse species highlights the biological complexity of these translocation systems and identifies common mechanistic themes as well as novel adaptations for specialized purposes relating to the modulation of the donor-target cell interaction.

Distributed Rate Allocation in Inter-Session Network Coding

In this work, we propose a distributed rate allocation algorithm that minimizes the average decoding delay for multimedia clients in inter-session network coding systems. We consider a scenario where the users are organized in a mesh network and each user requests the content of one of the available sources. We propose a novel distributed algorithm where network users determine the coding operations and the packet rates to be requested from the parent nodes, such that the decoding delay is minimized for all clients. A rate allocation problem is solved by every user, which seeks the rates that minimize the average decoding delay for its children and for itself. Since this optimization problem is a priori non-convex, we introduce the concept of equivalent packet flows, which permits to estimate the expected number of packets that every user needs to collect for decoding. We then decompose our original rate allocation problem into a set of convex subproblems, which are eventually combined to obtain an effective approximate solution to the delay minimization problem. The results demonstrate that the proposed scheme eliminates the bottlenecks and reduces the decoding delay experienced by users with limited bandwidth resources. We validate the performance of our distributed rate allocation algorithm in different video streaming scenarios using the NS-3 network simulator. We show that our system is able to take benefit of inter-session network coding for simultaneous delivery of video sessions in networks with path diversity.

Mobility and bandwidth prediction in virtualized LTE systems: Architecture and challenges

Long Term Evolution (LTE) represents the fourth generation (4G) technology which is capable of providing high data rates as well as support of high speed mobility. The EU FP7 Mobile Cloud Networking (MCN) project integrates the use of cloud computing concepts in LTE mobile networks in order to increase LTE's performance. In this way a shared distributed virtualized LTE mobile network is built that can optimize the utilization of virtualized computing, storage and network resources and minimize communication delays. Two important features that can be used in such a virtualized system to improve its performance are the user mobility and bandwidth prediction. This paper introduces the architecture and challenges that are associated with user mobility and bandwidth prediction approaches in virtualized LTE systems.

Shared Rule in Federal Political Systems: Conceptual Lessons from Subnational Switzerland

This article reconceptualizes shared rule and uses novel data to measure it, thus addressing two shortcomings of federal literature. First, while most studies focus on self-rule, one question that is largely neglected is how lower-level governments can influence politics at a higher level in the absence of “second” chambers. The answer is through shared rule. A second shortcoming is that even when addressing this question, scholars concentrate on constitutional-administrative aspects of vertical intergovernmentalism, neglecting more informal, “political” dynamics. Comparing the twenty-six Swiss cantons allows drawing two lessons for federal studies: That shared rule is multifaceted and complex, and that to study informal territorial actors as well as direct political processes is indispensable to understand how power is actually distributed in federal political systems.

Simulation of SLA-based VM-scaling algorithms for cloud-distributed applications

Cloud Computing has evolved to become an enabler for delivering access to large scale distributed applications running on managed network-connected computing systems. This makes possible hosting Distributed Enterprise Information Systems (dEISs) in cloud environments, while enforcing strict performance and quality of service requirements, defined using Service Level Agreements (SLAs). {SLAs} define the performance boundaries of distributed applications, and are enforced by a cloud management system (CMS) dynamically allocating the available computing resources to the cloud services. We present two novel VM-scaling algorithms focused on dEIS systems, which optimally detect most appropriate scaling conditions using performance-models of distributed applications derived from constant-workload benchmarks, together with SLA-specified performance constraints. We simulate the VM-scaling algorithms in a cloud simulator and compare against trace-based performance models of dEISs. We compare a total of three SLA-based VM-scaling algorithms (one using prediction mechanisms) based on a real-world application scenario involving a large variable number of users. Our results show that it is beneficial to use autoregressive predictive SLA-driven scaling algorithms in cloud management systems for guaranteeing performance invariants of distributed cloud applications, as opposed to using only reactive SLA-based VM-scaling algorithms.

A collaborative study on larval excretory/secretory antigens of Toxocara canis for the immunodiagnosis of human toxocariasis with ELISA.

Two batches of excretory/secretory (E/S) antigens from second stage larvae of Toxocara canis maintained in vitro were prepared independently in two different laboratories (Zürich and Basel) and analysed in order to obtain information for future efforts to standardize the enzyme-linked immunosorbent assay (ELISA) used for the serodiagnosis of human toxocariasis. SDS-PAGE and "Western-blotting" revealed at least 10 different antigenic components common to the two antigen preparations. However, distinct qualitative and quantitative differences among the two E/S-antigens were observed, since one antigen had a more complex composition than the other. Despite these differences, an accordance of serodiagnosis was obtained in 80% of 25 sera from patients with suspected Toxocara infection tested independently in two different ELISA systems (Basel and Zürich) with the corresponding E/S-antigens. The specificity was 93% as determined (BS-antigen, BS-ELISA) by testing 46 out of 3396 sera from patients with parasitologically proven extra-intestinal helminthic infections. Cross-reactions occurred mainly with sera from patients infected with filariae (5 from 13 cases) exhibiting very high extinction values in their homologous ELISA-system. The reproducibility (intra- and inter-test variations) of two ELISA systems using the corresponding E/S-antigens varied from 5-15%. The results demonstrate that T. canis E/S-antigens may well be applicable for standardization of the ELISA used for the serodiagnosis of human toxocariasis.

Service Level Agreements-Driven Management of Distributed Applications in Cloud Computing Environments

Cloud Computing enables provisioning and distribution of highly scalable services in a reliable, on-demand and sustainable manner. However, objectives of managing enterprise distributed applications in cloud environments under Service Level Agreement (SLA) constraints lead to challenges for maintaining optimal resource control. Furthermore, conflicting objectives in management of cloud infrastructure and distributed applications might lead to violations of SLAs and inefficient use of hardware and software resources. This dissertation focusses on how SLAs can be used as an input to the cloud management system, increasing the efficiency of allocating resources, as well as that of infrastructure scaling. First, we present an extended SLA semantic model for modelling complex service-dependencies in distributed applications, and for enabling automated cloud infrastructure management operations. Second, we describe a multi-objective VM allocation algorithm for optimised resource allocation in infrastructure clouds. Third, we describe a method of discovering relations between the performance indicators of services belonging to distributed applications and then using these relations for building scaling rules that a CMS can use for automated management of VMs. Fourth, we introduce two novel VM-scaling algorithms, which optimally scale systems composed of VMs, based on given SLA performance constraints. All presented research works were implemented and tested using enterprise distributed applications.

Bond Strength of Resin Composite to Dentin with Different Adhesive Systems: Influence of Relative Humidity and Application Time.

PURPOSE To investigate the influence of relative humidity and application time on bond strength to dentin of different classes of adhesive systems. MATERIALS AND METHODS A total of 360 extracted human molars were ground to mid-coronal dentin. The dentin specimens were treated with one of six adhesive systems (Syntac Classic, OptiBond FL, Clearfil SE Bond, AdheSE, Xeno Select, or Scotchbond Universal), and resin composite (Filtek Z250) was applied to the treated dentin surface under four experimental conditions (45% relative humidity/application time according to manufacturers' instructions; 45% relative humidity/reduced application time; 85% relative humidity/application time according to manufacturers' instructions; 85% relative humidity/reduced application time). After storage (37°C, 100% humidity, 24 h), shear bond strength (SBS) was measured and data analyzed with nonparametric ANOVA followed by Kruskal-Wallis tests and Mann-Whitney U-tests with Bonferroni-Holm correction for multiple testing (level of significance: α = 0.05). RESULTS Increased relative humidity and reduced application time had no effect on SBS for Clearfil SE Bond and Scotchbond Universal (p = 1.00). For Syntac Classic, OptiBond FL, AdheSE, and Xeno Select there was no effect on SBS of reduced application time of the adhesive system (p ≥ 0.403). However, increased relative humidity significantly reduced SBS for Syntac Classic, OptiBond FL, and Xeno Select irrespective of application time (p ≤ 0.003), whereas for AdheSE, increased relative humidity significantly reduced SBS at recommended application time only (p = 0.002). CONCLUSION Generally, increased relative humidity had a detrimental effect on SBS to dentin, but reduced application time had no effect.

Monitoring and Switching of First-line Antiretroviral Therapy in sub-Saharan Africa: Collaborative Analysis of Adult Treatment Cohorts.

BACKGROUND HIV-1 viral load (VL) testing is recommended to monitor antiretroviral therapy (ART) but not universally available. We examined monitoring of first-line and switching to second-line ART in sub-Saharan Africa, 2004-2013. METHODS Adult HIV-1 infected patients starting combination ART in 16 countries were included. Switching was defined as a change from a non-nucleoside reverse-transcriptase inhibitor (NNRTI)-based regimen to a protease inhibitor (PI)-based regimen, with a change of ≥1 NRTI. Virological and immunological failures were defined per World Health Organization criteria. We calculated cumulative probabilities of switching and hazard ratios with 95% confidence intervals (CI) comparing routine VL monitoring, targeted VL monitoring, CD4 cell monitoring and clinical monitoring, adjusted for programme and individual characteristics. FINDINGS Of 297,825 eligible patients, 10,352 patients (3·5%) switched during 782,412 person-years of follow-up. Compared to CD4 monitoring hazard ratios for switching were 3·15 (95% CI 2·92-3·40) for routine VL, 1·21 (1·13-1·30) for targeted VL and 0·49 (0·43-0·56) for clinical monitoring. Overall 58.0% of patients with confirmed virological and 19·3% of patients with confirmed immunological failure switched within 2 years. Among patients who switched the percentage with evidence of treatment failure based on a single CD4 or VL measurement ranged from 32·1% with clinical to 84.3% with targeted VL monitoring. Median CD4 counts at switching were 215 cells/µl under routine VL monitoring but lower with other monitoring (114-133 cells/µl). INTERPRETATION Overall few patients switched to second-line ART and switching occurred late in the absence of routine viral load monitoring. Switching was more common and occurred earlier with targeted or routine viral load testing.

BitWorker, a Decentralized Distributed Computing System based on BitTorrent

In this paper we present BitWorker, a platform for community distributed computing based on BitTorrent. Any splittable task can be easily specified by a user in a meta-information task file, such that it can be downloaded and performed by other volunteers. Peers find each other using Distributed Hash Tables, download existing results, and compute missing ones. Unlike existing distributed computing schemes relying on centralized coordination point(s), our scheme is totally distributed, therefore, highly robust. We evaluate the performance of BitWorker using mathematical models and real tests, showing processing and robustness gains. BitWorker is available for download and use by the community.

Protection of horses against Culicoides biting midges in different housing systems in Switzerland

Species belonging to the Culicoides complexes (Diptera, Ceratopogonidae), obsoletus and pulicaris, in Switzerland, are potential vectors of both bluetongue virus (BTV) and African horse sickness virus (AHSV). The epidemic of BTV in 2006 and 2007 in Europe has highlighted the risk of introduction and spread of vector-borne diseases in previously non-endemic areas. As a measure of prevention, as part of an integrated control programme in the event of an outbreak of African horse sickness (AHS), it is of utmost importance to prevent, or substantially reduce, contact between horses and Culicoides. The aim of the present study was to compare the effect of three protection systems, net, fan, repellent, or combinations thereof, with regard to their potential to reduce contact between horses and Culicoides. Three different equine housing systems, including individual boxes (BX), group housing systems (GR), and individual boxes with permanently accessible paddock (BP) were used. The efficacy of the protection systems were evaluated by comparing the total number counts of collected female Culicoides, of non-blood-fed and blood-fed Culicoides, respectively, with UV black light traps. The study was conducted over 3 summer months during 2012 and 2013 each and focused on the efficacy and practicality of the protection systems. The repellent was tested in 2012 only and not further investigated in 2013, as it showed no significant effect in reducing Culicoides collected in the light traps. Net protection system provided the best overall protection for the total number of female Culicoides, non-blood-fed and blood-fed Culicoides in all tested housing systems. The net, with a pore size of 0.1825 mm(2), reduced the total number of Culicoides collected in the housing systems BP, GR and BX by 98%, 85% and 67%, respectively. However, in the GR housing system, no significant difference between the effectiveness of the fan and the net were determined for any of the three Culicoides categories. The results of the present study demonstrated that horse owners can substantially reduce their horses' exposure to Culicoides, by using net protection in the housing systems BX, BP and GR. In GR housing systems, protection against Culicoides using a fan is also recommended.

Service level agreements-driven management of distributed applications in cloud computing environments

Advancements in cloud computing have enabled the proliferation of distributed applications, which require management and control of multiple services. However, without an efficient mechanism for scaling services in response to changing workload conditions, such as number of connected users, application performance might suffer, leading to violations of Service Level Agreements (SLA) and possible inefficient use of hardware resources. Combining dynamic application requirements with the increased use of virtualised computing resources creates a challenging resource Management context for application and cloud-infrastructure owners. In such complex environments, business entities use SLAs as a means for specifying quantitative and qualitative requirements of services. There are several challenges in running distributed enterprise applications in cloud environments, ranging from the instantiation of service VMs in the correct order using an adequate quantity of computing resources, to adapting the number of running services in response to varying external loads, such as number of users. The application owner is interested in finding the optimum amount of computing and network resources to use for ensuring that the performance requirements of all her/his applications are met. She/he is also interested in appropriately scaling the distributed services so that application performance guarantees are maintained even under dynamic workload conditions. Similarly, the infrastructure Providers are interested in optimally provisioning the virtual resources onto the available physical infrastructure so that her/his operational costs are minimized, while maximizing the performance of tenants’ applications. Motivated by the complexities associated with the management and scaling of distributed applications, while satisfying multiple objectives (related to both consumers and providers of cloud resources), this thesis proposes a cloud resource management platform able to dynamically provision and coordinate the various lifecycle actions on both virtual and physical cloud resources using semantically enriched SLAs. The system focuses on dynamic sizing (scaling) of virtual infrastructures composed of virtual machines (VM) bounded application services. We describe several algorithms for adapting the number of VMs allocated to the distributed application in response to changing workload conditions, based on SLA-defined performance guarantees. We also present a framework for dynamic composition of scaling rules for distributed service, which used benchmark-generated application Monitoring traces. We show how these scaling rules can be combined and included into semantic SLAs for controlling allocation of services. We also provide a detailed description of the multi-objective infrastructure resource allocation problem and various approaches to satisfying this problem. We present a resource management system based on a genetic algorithm, which performs allocation of virtual resources, while considering the optimization of multiple criteria. We prove that our approach significantly outperforms reactive VM-scaling algorithms as well as heuristic-based VM-allocation approaches.

Object-Based Customization of Learning Content: Potentials and Pitfalls

Specification consortia and standardization bodies concentrate on e-Learning objects to en-sure reusability of content. Learning objects may be collected in a library and used for deriv-ing course offerings that are customized to the needs of different learning communities. How-ever, customization of courses is possible only if the logical dependencies between the learn-ing objects are known. Metadata for describing object relationships have been proposed in several e-Learning specifications. This paper discusses the customization potential of e-Learning objects but also the pitfalls that exist if content is customized inappropriately.