The Phylogenetic Likelihood Library

[Abstract] We introduce the Phylogenetic Likelihood Library (PLL), a highly optimized application programming interface for developing likelihood-based phylogenetic inference and postanalysis software. The PLL implements appropriate data structures and functions that allow users to quickly implement common, error-prone, and labor-intensive tasks, such as likelihood calculations, model parameter as well as branch length optimization, and tree space exploration. The highly optimized and parallelized implementation of the phylogenetic likelihood function and a thorough documentation provide a framework for rapid development of scalable parallel phylogenetic software. By example of two likelihood-based phylogenetic codes we show that the PLL improves the sequential performance of current software by a factor of 2–10 while requiring only 1 month of programming time for integration. We show that, when numerical scaling for preventing floating point underflow is enabled, the double precision likelihood calculations in the PLL are up to 1.9 times faster than those in BEAGLE. On an empirical DNA dataset with 2000 taxa the AVX version of PLL is 4 times faster than BEAGLE (scaling enabled and required).DFG, German Research Foundation; STA/860-4. F.I.-C.DFG, German Research Foundation; STA/860-3DFG, German Research Foundation; STA/860-2. L.-T.N.University of Vienna; I059-NAustrian Science Fund; I760-B1

Improving the Throughput of Distributed Hash Tables Using Congestion-Aware Routing

Advanced applications for Distributed Hash Tables (DHTs), such as Peer-to-Peer Information Retrieval, require a DHT to quickly and efficiently process a large number (in the order of millions) of requests. In this paper we study mechanisms to optimize the throughput of DHTs. Our goal is to maximize the number of route operations per peer per second a DHT can perform (given certain constraints on the lookup delay). Each peer receives congestion feedback from the DHT, which it uses to adjust its routing decisions. This way, peers can avoid routing through slow parts of the overlay network and hence increase the rate at which they insert new messages into the DHT.We provide a numerical analysis of congestion-aware routing in DHTs and show that considerable improvements in throughput are possible compared to DHTs with proximity neighbor selection and strictly greedy routing

Allergologische Diagnostik von Überempfindlichkeitsreaktionen auf Arzneimittel

Überempfindlichkeitsreaktionen auf Arzneimittel müssen ausreichend geklärt werden mit dem Ziel, den Auslöser zu identifizieren. Die Anamnese umfasst neben der allgemeinen Anamnese auch Informationen zu angewandten Arzneimitteln, zur Klassifikation und zu den Umständen der Reaktion. Hauttests erfolgen bei allen Reaktionen mit Symptomen allergischer Überempfindlichkeiten mit geeigneten Testkonzentrationen, möglichst zwischen 4 Wochen und 6 Monate nach Abheilung der Reaktion durch Pricktest, Intrakutantest, Epikutantest oder Photopatchtest. Validierte Tests zum Nachweis spezifischer IgE-Antikörper im Serum sind nur für wenige Arzneistoffe (vor allem Betalaktamantibiotika) verfügbar; andere immunologische Labormethoden, z.B. der Basophilen-Aktivierungstest, werden nur in ausgewählten Fällen angewendet. Provokationstests sind indiziert, wenn der Auslöser durch bisherige Untersuchungen nicht mit Sicherheit identifiziert werden kann. Die Bewertung der Ergebnisse von Provokationstests sollte möglichst anhand objektiver Parameter erfolgen. Das Ergebnis der abschließenden Gesamtbeurteilung wird mit dem Patienten ausführlich besprochen und in einem Allergiepass niedergeleg

Allergologische Diagnostik von Überempfindlichkeitsreaktionen auf Arzneimittel

Drug hypersensitivity reactions have to be tested to identify the culprit substance. The history includes the general information and specific data concerning used drugs, the classification and circumstances of the reaction. Skin tests are performed in all hypersensitivity reactions with allergic symptoms. Tests should be done between four weeks and six months after clearance of the symptoms by performing skin prick test, intradermal test, patch test or photopatch test. Validated tests for the detection of specific IgE antibodies in the serum are available for only few drugs, especially betalactam antibiotics. Other laboratory tests, e.g., the basophil activation test are done only in special cases. Provocation tests are indicated, if the culprit drug cannot be identified by the above mentioned tests. If possible, the evaluation of provocation tests should rely on objective parameters. The concluding assessment will be discussed with the patient and will be documented in an allergy pass

Towards a global participatory platform: Democratising open data, complexity science and collective intelligence

The FuturICT project seeks to use the power of big data, analytic models grounded in complexity science, and the collective intelligence they yield for societal benefit. Accordingly, this paper argues that these new tools should not remain the preserve of restricted government, scientific or corporate élites, but be opened up for societal engagement and critique. To democratise such assets as a public good, requires a sustainable ecosystem enabling different kinds of stakeholder in society, including but not limited to, citizens and advocacy groups, school and university students, policy analysts, scientists, software developers, journalists and politicians. Our working name for envisioning a sociotechnical infrastructure capable of engaging such a wide constituency is the Global Participatory Platform (GPP). We consider what it means to develop a GPP at the different levels of data, models and deliberation, motivating a framework for different stakeholders to find their ecological niches at different levels within the system, serving the functions of (i) sensing the environment in order to pool data, (ii) mining the resulting data for patterns in order to model the past/present/future, and (iii) sharing and contesting possible interpretations of what those models might mean, and in a policy context, possible decisions. A research objective is also to apply the concepts and tools of complexity science and social science to the project's own work. We therefore conceive the global participatory platform as a resilient, epistemic ecosystem, whose design will make it capable of self-organization and adaptation to a dynamic environment, and whose structure and contributions are themselves networks of stakeholders, challenges, issues, ideas and arguments whose structure and dynamics can be modelled and analysed. Graphical abstrac

An Optimal Broadcast Algorithm for Content-Addressable Networks

International audienceStructured peer-to-peer networks are powerful underlying structures for communication and storage systems in large-scale setting. In the context of the Content-Addressable Network (CAN), this paper addresses the following challenge: how to perform an efficient broadcast while the local view of the network is restricted to a set of neighbours? In existing approaches, either the broadcast is inefficient (there are dupli- cated messages) or it requires to maintain a particular structure among neighbours, e.g. a spanning tree. We define a new broadcast primitive for CAN that sends a minimum number of messages while covering the whole network, without any global knowledge. Currently, no other al- gorithm achieves those two goals in the context of CAN. In this sense, the contribution we propose in this paper is threefold. First, we pro- vide an algorithm that sends exactly one message per recipient without building a global view of the network. Second, we prove the absence of duplicated messages and the coverage of the whole network when using this algorithm. Finally, we show the practical benefits of the algorithm throughout experiments

A Novel DC Therapy with Manipulation of MKK6 Gene on Nickel Allergy in Mice

BACKGROUND: Although the activation of dermal dendritic cells (DCs) or Langerhans cells (LCs) via p38 mitogen-activated protein kinase (MAPK) plays a crucial role in the pathogenesis of metal allergy, the in vivo molecular mechanisms have not been identified and a possible therapeutic strategy using the control of dermal DCs or LCs has not been established. In this study, we focused on dermal DCs to define the in vivo mechanisms of metal allergy pathogenesis in a mouse nickel (Ni) allergy model. The effects of DC therapy on Ni allergic responses were also investigated. METHODS AND FINDING: The activation of dermal DCs via p38 MAPK triggered a T cell-mediated allergic immune response in this model. In the MAPK signaling cascade in DCs, Ni potently phosphorylated MAP kinase kinase 6 (MKK6) following increased DC activation. Ni-stimulated DCs could prime T cell activation to induce Ni allergy. Interestingly, when MKK6 gene-transfected DCs were transferred into the model mice, a more pronounced allergic reaction was observed. In addition, injection of short interfering (si) RNA targeting the MKK6 gene protected against a hypersensitivity reaction after Ni immunization. The cooperative action between T cell activation and MKK6-mediated DC activation by Ni played an important role in the development of Ni allergy. CONCLUSIONS: DC activation by Ni played an important role in the development of Ni allergy. Manipulating the MKK6 gene in DCs may be a good therapeutic strategy for dermal Ni allergy

The registry of the German Network for Systemic Scleroderma: frequency of disease subsets and patterns of organ involvement

Objective. Systemic sclerosis (SSc) is a rare, heterogeneous disease, which affects different organs and therefore requires interdisciplinary diagnostic and therapeutic management. To improve the detection and follow-up of patients presenting with different disease manifestations, an interdisciplinary registry was founded with contributions from different subspecialties involved in the care of patients with SSc