Miniaturized fibre-top cantilevers on etched fibres

Fibre-top probes are self-aligned, all optical devices obtained by carving a cantilever on top of a 125-μm diameter single-mode optical fibre. In this paper, we show that this design can be adapted to smaller fibres as well. We evaluated the performance of a 20-μm diameter probe in contact mode atomic force microscopy (AFM) and that of a 50-μm diameter probe in nanoindentation measurements. AFM images proved to be accurate both in air and water, although some distortion was observed because of the mechanical bending of the fibre during scanning. Indentation curves resembled those obtained with larger devices. The maximum indentation depth, however, is limited by the small dimensions of the cantilever

Nearest-neighbour directed random hyperbolic graphs

Undirected hyperbolic graph models have been extensively used as models of scale-free small-world networks with high clustering coefficient. Here we presented a simple directed hyperbolic model, where nodes randomly distributed on a hyperbolic disk are connected to a fixed number m of their nearest spatial neighbours. We introduce also a canonical version of this network (which we call "network with varied connection radius"), where maximal length of outgoing bond is space-dependent and is determined by fixing the average out-degree to m. We study local bond length, in-degree and reciprocity in these networks as a function of spatial coordinates of the nodes, and show that the network has a distinct core-periphery structure. We show that for small densities of nodes the overall in-degree has a truncated power law distribution. We demonstrate that reciprocity of the network can be regulated by adjusting an additional temperature-like parameter without changing other global properties of the network.Comment: 26 papers, 12 figure

On the evolution of decoys in plant immune systems

The Guard-Guardee model for plant immunity describes how resistance proteins (guards) in host cells monitor host target proteins (guardees) that are manipulated by pathogen effector proteins. A recently suggested extension of this model includes decoys, which are duplicated copies of guardee proteins, and which have the sole function to attract the effector and, when modified by the effector, trigger the plant immune response. Here we present a proof-of-principle model for the functioning of decoys in plant immunity, quantitatively developing this experimentally-derived concept. Our model links the basic cellular chemistry to the outcomes of pathogen infection and resulting fitness costs for the host. In particular, the model allows identification of conditions under which it is optimal for decoys to act as triggers for the plant immune response, and of conditions under which it is optimal for decoys to act as sinks that bind the pathogen effectors but do not trigger an immune response.Comment: 15 pages, 6 figure

A critical evaluation of spectrum-based fault localization techniques on a large-scale software system

In the past, spectrum-based fault localization (SBFL) techniques have been developed to pinpoint a fault location in a program given a set of failing and successful test executions. Most of the algorithms use similarity coefficients and have only been evaluated on established but small benchmark programs from the Software-artifact Infrastructure Repository (SIR). In this paper, we evaluate the feasibility of applying 33 state-of-the-art SBFL techniques to a large real-world project, namely ASPECTJ. From an initial set of 350 faulty version from the iBugs repository of ASPECTJ we manually classified 88 bugs where SBFL techniques are suitable. Notably, only 11 bugs of these bugs can be found after examining the 1000 most suspicious lines and on average 250 source code files need to be inspected per bug. Based on these results, the study showcases the limitations of current SBFL techniques on a larger program

Opto-mechanical probe for combining atomic force microscopy and optical near-field surface analysis

We have developed a new easy-to-use probe that can be used to combine atomic force microscopy (AFM) and scanning near-field optical microscopy (SNOM). We show that, using this device, the evanescent field, obtained by total internal reflection conditions in a prism, can be visualized by approaching the surface with the scanning tip. Furthermore, we were able to obtain simultaneous AFM and SNOM images of a standard test grating in air and in liquid. The lateral resolution in AFM and SNOM mode was estimated to be 45 and 160 nm, respectively. This new probe overcomes a number of limitations that commercial probes have, while yielding the same resolution. (C) 2014 Optical Society of Americ

The development of PubMed search strategies for patient preferences for treatment outcomes.

BACKGROUND: The importance of respecting patients' preferences when making treatment decisions is increasingly recognized. Efficiently retrieving papers from the scientific literature reporting on the presence and nature of such preferences can help to achieve this goal. The objective of this study was to create a search filter for PubMed to help retrieve evidence on patient preferences for treatment outcomes. METHODS: A total of 27 journals were hand-searched for articles on patient preferences for treatment outcomes published in 2011. Selected articles served as a reference set. To develop optimal search strategies to retrieve this set, all articles in the reference set were randomly split into a development and a validation set. MeSH-terms and keywords retrieved using PubReMiner were tested individually and as combinations in PubMed and evaluated for retrieval performance (e.g. sensitivity (Se) and specificity (Sp)). RESULTS: Of 8238 articles, 22 were considered to report empirical evidence on patient preferences for specific treatment outcomes. The best search filters reached Se of 100 % [95 % CI 100-100] with Sp of 95 % [94-95 %] and Sp of 97 % [97-98 %] with 75 % Se [74-76 %]. In the validation set these queries reached values of Se of 90 % [89-91 %] with Sp 94 % [93-95 %] and Se of 80 % [79-81 %] with Sp of 97 % [96-96 %], respectively. CONCLUSIONS: Narrow and broad search queries were developed which can help in retrieving literature on patient preferences for treatment outcomes. Identifying such evidence may in turn enhance the incorporation of patient preferences in clinical decision making and health technology assessment

RADON: Rational decomposition and orchestration for serverless computing

Emerging serverless computing technologies, such as function as a service (FaaS), enable developers to virtualize the internal logic of an application, simplifying the management of cloud-native services and allowing cost savings through billing and scaling at the level of individual functions. Serverless computing is therefore rapidly shifting the attention of software vendors to the challenge of developing cloud applications deployable on FaaS platforms. In this vision paper, we present the research agenda of the RADON project (http://radon-h2020.eu), which aims to develop a model-driven DevOps framework for creating and managing applications based on serverless computing. RADON applications will consist of fine-grained and independent microservices that can efficiently and optimally exploit FaaS and container technologies. Our methodology strives to tackle complexity in designing such applications, including the solution of optimal decomposition, the reuse of serverless functions as well as the abstraction and actuation of event processing chains, while avoiding cloud vendor lock-in through models

Balancing Selection at the Tomato RCR3 Guardee Gene Family Maintains Variation in Strength of Pathogen Defense

Coevolution between hosts and pathogens is thought to occur between interacting molecules of both species. This results in the maintenance of genetic diversity at pathogen antigens (or so-called effectors) and host resistance genes such as the major histocompatibility complex (MHC) in mammals or resistance (R) genes in plants. In plant-pathogen interactions, the current paradigm posits that a specific defense response is activated upon recognition of pathogen effectors via interaction with their corresponding R proteins. According to the''Guard-Hypothesis,'' R proteins (the ``guards'') can sense modification of target molecules in the host (the ``guardees'') by pathogen effectors and subsequently trigger the defense response. Multiple studies have reported high genetic diversity at R genes maintained by balancing selection. In contrast, little is known about the evolutionary mechanisms shaping the guardee, which may be subject to contrasting evolutionary forces. Here we show that the evolution of the guardee RCR3 is characterized by gene duplication, frequent gene conversion, and balancing selection in the wild tomato species Solanum peruvianum. Investigating the functional characteristics of 54 natural variants through in vitro and in planta assays, we detected differences in recognition of the pathogen effector through interaction with the guardee, as well as substantial variation in the strength of the defense response. This variation is maintained by balancing selection at each copy of the RCR3 gene. Our analyses pinpoint three amino acid polymorphisms with key functional consequences for the coevolution between the guardee (RCR3) and its guard (Cf-2). We conclude that, in addition to coevolution at the ``guardee-effector'' interface for pathogen recognition, natural selection acts on the ``guard-guardee'' interface. Guardee evolution may be governed by a counterbalance between improved activation in the presence and prevention of auto-immune responses in the absence of the corresponding pathogen

The ELF Honest Data Broker:Informatics enabling public-private collaboration in a precompetitive arena

New precompetitive ways of working in the pharmaceutical industry are driving the development of new informatics systems to enable their execution and management. The European Lead Factory (ELF) is a precompetitive, 30-partner collaboration between academic groups, small–medium enterprises and pharmaceutical companies created to discover small molecule hits against novel biological targets. A unique HTS screening and triage workflow has been developed to balance the intellectual property and scientific requirements of all the partners. Here, we describe the ELF Honest Data Broker, a cloud-based informatics system providing the scientific triage tools, fine-grained permissions and management tools required to implement the workflow