dataesr/scientific-paragraphs-categorization huggingface dataset:
, 2010b). The building of next generation of GW instruments is underway, with data collection expected to start around 2015. Following Abadie et al. (2010b), source population models imply that direct detection of gravitational waves can be achieved within the next decade by such advanced ground-based GW detectors: advanced LIGO 14  in the USA  (Harry, 2010) , Advanced VIRGO 15  in Italy and KAGRA in Japan  (Kuroda, 2010). There is now a proposal (still to be approved by U. S. and Indian institutions) to move one of the three advanced LIGO detectors at a new observatory in India. If this plan materializes, the detector at the Indian site would start operation around 2020. These detectors will offer a tenfold sensitivity increase over the initial detectors around 100Hz and will extend the observable frequency range by almost a decade down to 10Hz.
6 ). ANTARES has been joined by the two prototype projects NEMO  (Taiuti, 2011)  and NESTOR  (Rapidis, 2009)  in forming the European Consortium KM3NeT which aims at the construction of a km 3 scale telescope in the Mediterranean, whose operation could start in 2014  (Katz, 2011). This second kilometer-scale project would allow all-sky coverage, and in particular the monitoring of a large fraction of the Galactic Plane, which contains many potential sources. An interesting characteristic of these detectors is the ability to take data during the construction phase; each data taking configuration is labelled by the number of functioning detector lines (or strings). Detector performance, as measured by e. g. effective area and pointing accuracy, then improves as new lines are added. The time chart in Fig.
If this is detected in real-time, then neutrino telescopes can be used as triggers for optical, x-ray, and gamma-ray follow-ups. IceCube and ANTARES currently have alert programs established or in development with fast optical telescope networks like ROTSE and TAROT, gamma-ray telescopes such as Swift, Fermi, MAGIC, and VERITAS; see e. g. Franckowiak et al. (2009 ), Van Elewyck (2011 ), Ageron et al. (2012). The ROTSE optical follow-up program implemented for neutrino multiplets detected with IceCube has e. g. been used to search for soft relativistic jets in core-collapse supernovae, yielding negative results so far  (Abbasi et al. , 2012d). "All-sky" instruments like neutrino telescopes and GW detectors thus provide an opportunity to alert pointing instruments before or concurrent with an interesting astronomical event, in addition to enabling more powerful joint searches for bursts in a completely offline way after the data has been recorded.
It should be noted that an analogous possibility exists for much lower energy neutrinos. Because the PMT dark noise rate is particularly low in ice, the IceCube detector is sensitive to sudden fluxes of MeV neutrinos which lead to collective rise in the PMT rates. Nearby supernova up to 50 kpc can be detected this way. IceCube is therefore part of the SuperNova Early Warning System (SNEWS), sending real-time triggers when the collective PMT rate passes a given threshold; see  Kowarik et al. (2009)  and  Abbasi et al. (2011b). As with high energy neutrino data, an offline analysis with other all-sky instruments, like GW detectors, is also possible. While the MeV neutrino signal does not provide any directional information, the time-coincidence search would allow exploring the data below the higher threshold required for SNEWS  (Halzen and Raffelt, 2009).
B. HEN data analysis The searches for astrophysical point-sources of HEN rely principally on charged-current interactions of muon neutrinos. At the energies probed by neutrino telescopes, the outgoing muon can travel from hundreds of meters up to many kilometers, and the direction of the muon is nearly collinear with the original direction of the neutrino. Cherenkov photons propagating from the track are detected by the array of photo-multiplier tubes, and the relative timing of the photon hits is used to reconstruct the muon direction. The angular resolution is limited by the number of hits detected and by any distortions in the photon arrival times due to scattering in the water or ice. Higher energy muons are generally better reconstructed, since they travel farther, providing a longer lever arm for reconstruction, and since more photons are emitted in stochastic energy losses along the path.
Thus, the use of an external trigger can be a very effective tool for a successful search of GW signals. A variety of algorithms for triggered searches have been developed. We will focus here on two examples which are currently used in the context of HEN-triggered searches: the burst search algorithm dubbed as X-pipeline  (Sutton et al. , 2010) , and the STAMP search algorithm for extended GW emission  (Thrane et al. , 2011). The X-Pipeline is a coherent technique that has been used to perform searches for GWs in association with GRBs  (Abbott et al. , 2010). It is a software package designed for autonomous searches for unmodelled GW bursts. It targets GW bursts associated with external astrophysical "triggers" such as GRBs or neutrinos. It performs a coherent analysis of data from arbitrary networks of GW detectors, while being robust against noise-induced glitches.
A crucial part of the procedure is the estimation of the background distributions, which is performed on the data pertaining to an off-source time window, typically covering about 1. 5 hours around the neutrino time trigger and excluding the on-source interval. This strategy ensures that the background does not contain any signal associated with the neutrino event but has similar statistical features as the data searched in association with the neutrino. This time range is limited enough so that the detectors should be in a similar state of operation as during the neutrino on-source interval, but long enough to provide off-source segments for estimating the background. A schematic flowchart of this analysis strategy is presented in Fig. 8. A GW burst search with the X-Pipeline was performed using a list of 158 ANTARES 5L neutrino candidates as external triggers.
Some of these channels have already been used both in searches for GWs with the LIGO-GEO-Virgo interferometer network, and in searches for HEN with the current neutrino telescopes ANTARES and IceCube. However, many of the emission models for these astrophysical objects have so far been indistinguishable by electromagnetic observations. The combination of two weakly interacting messengers, GWs and HENs, therefore provides a new and exciting opportunity for multimessenger searches with different challenges and outcomes from observations using electromagnetic counterparts. Such a joint GW+HEN analysis program could significantly expand the scientific reach of both GW interferometers and HEN telescopes. The robust background rejection arising from the combination of two totally independent sets of data results in an increased sensitivity and the possible recovery of cosmic signals.
In the promising case of GRBs, the outcome of a joint GW+HEN search could e. g. improve our understanding of the details of astrophysical processes connecting the gravitational collapse/merger of compact objects to black-hole formation as well as to the formation of fireballs. Several periods of concurrent observations with GW and HEN detectors have already taken place and the corresponding data are being scrutinized for coincident GW+HEN signals. Future schedules involving next-generation detectors with a significantly increased sensitivity (such as KM3NeT and the advanced LIGO/Advanced Virgo projects) are likely to coincide as well. Studies are ongoing to explore the reach of current and planned experiments in constraining the population of multimessenger sources of GWs and HENs, with or without electromagnetic counterpart  (Bartos et al.
They are then singled onto fresh plates, grown and pooled before DNA is extracted and sequenced. From the deep sequencing data and with the use of available software,  34  a genomic region linked to the causal mutation will be identified and nucleotide mutations within this region will also be revealed. A list of candidate causal mutations that affect genes within this region will also be assembled. The original mutant is then subjected to multiple rounds of backcrossing or outcrossing (≥ six simple backcrosses or equivalent recommended) to remove all other EMS-induced mutations from its background and then tested via several methods (e. g. , complementation analysis and transgenic rescue) to determine which candidate mutation is causing the phenotype.
Analyzing Deep Sequencing Data Analyzing deep sequencing results from C. elegans was aided by the development of programs such as MAQgene,  38  which uses the assembly building software MAQ. 39 Although once useful, MAQ is now an outdated aligner and installation of MAQgene required specialized bioinformatic expertise. More recently, a cloud-based pipeline called CloudMap was developed, which is entirely Internet-based and therefore does not require any software installation. 34 This latest development allows users to choose from several aligners including the Burrows-Wheeler Aligner (BWA)  40  and Bowtie. 41 With CloudMap, a specific map position and list of candidate variants from raw sequencing data from all major NGS platforms (Illumina, ABI, 454) can be obtained using either of the different mapping strategies discussed in this review (EMS-based and SNP-based mapping).
Figure2. Flowchart of SNP-based simultaneous mapping and mutant identification using deep sequencing. This strategy is similar to traditional SNP mapping techniques performed before whole genome sequencing was feasible. However, instead of analyzing the linkage of SNPs to a causal mutation one at a time through laborious identification procedures, deep sequencing is used to interrogate most of them simultaneously (see ref. 21). Twenty to 50 F 2 progeny displaying the mutant phenotype are picked from a cross between the mutant (usually in a Bristol N2 background) and a polymorphic strain such as CB4856. They are then singled onto fresh plates, grown and pooled before DNA is extracted and sequenced. From the deep sequencing data and with the use of available software, 34  a genomic region linked to the causal mutation will be identified and nucleotide mutations within this region will also be revealed.
Acknowledgments We acknowledge the helpful comments of members of the  Jarriault Lab as well as Oliver Hobert. This work was supported by a  Fondation ARC (Association pour la Recherche sur le Cancer)   Postdoctoral Fellowship  (to S. Z. ) and grants from the  Centre National de la Recherche Scientifique-ATIP  ( Action Thématique Incitative sur Programme ), the  Fondation pour la Recherche Médicale  ( FRM-DRC20091217181 ), and  European Molecular Biology Organization (EMBO) Young Investigator Prize  (to S. J. ). S. J. is an investigator of the  Centre National de la Recherche Scientifique.
, 2010). However, our proof-of-concept implementation only allowed for its application on very small data sets, and its rate-limiting Markov chain Monte Carlo (MCMC) updates on the Dirichlet process, based on a Chinese-restaurant approach, were not amendable to parallelization. Working with nucleotide and amino acid level substitution models, we recently developed PhyloBayes-MPI, which, among other speedup strategies, uses message-passing-interface (MPI) and a truncated stick-breaking representation of the Dirichlet process for parallelized updating  (Lartillot et al. , 2013). Here, we have expanded PhyloBayes-MPI for the implementation of several types of codon substitution models, including the Dirichlet process-based site-heterogeneous mutation-selection approach. We illustrate how the software can now be used for efficient estimation of distributions of selection coefficients (scaled by the effective chromosomal population size), and discuss several future avenues that it enables.
METHODS In the present application, the program is passed an alignment file of coding nucleotide sequences (of a length that is a factor of 3) and a corresponding tree topology file. The universal genetic code is assumed, but an alternative code can be specified (e. g. -mtvert for the vertebrate mitochondrial code). As with other models with PhyloBayes-MPI, the program uses K41 cores. At startup, the master core draws an initial model configuration from the prior, and broadcasts it using MPI to the K À 1 compute cores. All updates are data-augmentation-based, which are several orders of magnitude faster than pruning-based updates (de  Koning et al. , 2010). Each iteration of the MCMC includes numerous updates on global parameters, performed by the master core, whereas compute cores perform several updates of a truncated stick-breaking representation of the Dirichlet process (see  Lartillot et al.
FUTURE DIRECTIONS Our implementation enables numerous potential applications. For instance, the last panel of Figure  1  suggests studies on the distributions of S over classes of sites. Distributions could even be generated for all possible types of nonsynonymous mutations at each site. The software could also serve in the development of approaches that explicitly incorporate structural features (e. g. Meyer and Wilke, 2013) , and already includes mutation-selection models using finite mixtures, homogeneous versions and models based on a univariate factor on nonsynonymous rates (!). Applications of these models will be the focus of future papers. Developed within the PhyloBayes-MPI package, the models we have implemented here inherit the ability to perform a variety of types of posterior predictive model assessments, cross-validation comparisons, ancestral sequence reconstruction, as well as phylogenetic inference per se.
This paper illustrates an overview of our methodology for producing 3D models of Cultural Heritage structures such as monuments and artefacts from 2D data (pictures, video), available on Internet repositories, social media, Google Maps, Bing, etc. We also present new approaches to semantic enrichment of the end results and their subsequent export to Europeana, the European digital library, for integrated, interactive 3D visualisation within regular web browsers using WebGl and X3D. Our main goal is to enable historians, architects, archaeologists, urban planners and affiliated professionals to reconstruct views of historical structures from millions of images floating around the web and interact with them.
VISUAL SEARCH ENGINE In Figure  1 , we present a schematic diagram of our search engine (Eagle4D) used for visual content retrieval appropriate for CH objects. The engine is applied on the web and thus it searches objects in the "wild" visual content. Then, the results are improved by exploiting metadata from Europeana and/or Memory of the World. In this section, we propose a recursive methodology for estimating corresponding points from a set of unstructured and un-calibrated images. In particular, the method exploits local descriptors for finding the most prominent points in an image, which then are used as vertex of a graph. In this way, we construct a graph, the vertices of which coincides with the feature points while the edges the distance between two selected features. In our approach, geometrically invariant features have been selected and especially the SIFT transform.
The IVB enables fusion and annotation of a variety of multimedia context information from different sources belonging to a digitised 3D artefact, consolidation of all pieces of information and export of the datasets to Europeana using its ESE (Europeana Semantic Elements) metadata format, a Dublin Core-based set of fields with 12 additional specific Europeana elements to display records appropriately. This semantic enrichment tool will be the focus of future research for further development in order to include the 4th dimension (time) as well as further details related to the origin of the data and the historical value of the object (depending on the application for the re-use of the final 3D results). represented by an image of its main entrance.
Recent Internet of Things (IoT) research has been aiming at interoperability of devices and the integration of sensor networks. The Future Internet -Private Public Partnership (FI-PPP) has created a whole array of different purpose-oriented modules with defined specifications, better known as Generic Enablers. This article gives an overview of legal, ethical and technical norms and standards to be considered when planning, developing and implementing modular medical architectures, integrating the Internet of Things (IoT) and Generic Enablers (GEs) in cutting edge, latest generation medical data networks.
With the arrival of new architectural concepts driven by the European Commission's Future Internet Private Public Partnership (FI-PPP) the attention has shifted towards what has become known as the Core Platform and the "Generic Enablers" (GE) which now in some respect forms the flipside of the coin  [3]. The Generic Enablers need to be regarded as modules or building blocks, which can be utilized to generate instantiations, which generate a defined functionality. In the GE Universe functionality is primarily defined by the interaction of different GEs, whereby the interface specifications are clearly defined in a catalogue  [4]. The future will show how these 2 fundamental technology flows will merge, coexist or kick-start completely new developments. However, if smart devices, sensors and mobile computers are to evolve further and are linked as part of modular medical architectures driven by GE technology a variety of norms and standards on a national, European and International level need to be considered by developers, healthcare providers and other user groups.
[26]  Alternatively, implementations might constitute electronic communication services, if they provide a service for users with telecommunications functionality (without the provider exercising editorial control over conveyed signals). These services involve various obligations concerning universal access, user rights, and data protection. [27]  More likely, modular medical architectures may be qualified as medical devices, i. e. , an instrument, apparatus, appliance, software, material or other article, intended to be used for diagnostic and / or therapeutic purposes, which does not function through pharmacological, immunological or metabolic means. General software, including Generic Enablers, used in e-health is not a medical device, but software manufactured or specifically adapted for medical purposes is a medical device.
To enable independence from the manufacturer of these products, ISO/IEEE 11073 specifies how the products interact. It is a family of standards that defines the application domain, terms, information model, types of devices, applications, data transport, and data encoding. ETSI ES 202 975, even-though not specific for the health domain, further constrains communication of text, speech, and video in a network. Information that is of particular relevance in the care sector is the patient profile. CEN/TC 251 has developed a collection of standards on health informatics for health interoperability. CEN/ISO 13606 is of particular importance as it specifies electronic health record communication. It captures a reference model that allows the formulation and aggregation of statements of relevance for the health record, an archetype model that defines health concepts and their meaning, and allows defining data protection rules that govern the access to the data the health record contains.
This means that typically software has to comply in full with national medical product legislation. There is good evidence that future "medical" architectures will be modular and follow European wide defined specifications. Health care providers have rejected public ehealth cloud approaches in Europe and elsewhere and single standing solutions are unlikely to continue due to regulations and cost aspects. There has been good progress fueled by EC funded research with regards to the cross border transfer of medical data sets within Europe  [48]. Our future work under FI-STAR will include a mapping of the standards discussed in this paper onto Generic Enablers and Usage Specific Enablers. As part of our progressive work we will also map those standards, which so far could not be considered, such as the US standards and legislation in different European national states.
VI. CONCLUSIONS Legal norms, ethical opinions and technological standards have to be considered when planning, designing and implementing medical modular architectures based on IoT elements and Generic Enablers. In principle these norms and standards do not distinguish between hardware and software technologies or IoT and the Core Platform. In most countries software products now have to comply fully with the national medical product legislation, which has not always been the case. Although regulations are complex and diverse and might be perceived as hurdle or obstacle on the way to the development of new technologies staff and patient's rights have to be considered and health and safety must have first priority. A detailed requirements analysis is inevitable in order to assure full compliance with regulations of new technologies and to avoid unexpected costs for adjustments and adaptation at a late stage in the development process.
The advent of successful commercial software for whole body modeling such as SimCyp, which can incorporate inter-individual variability (physiological, CYP genotype and gastro-intestinal absorption) has made prediction of clearance integral with prediction of pharmacokinetics a routine procedure  (Howgate et al. 2006; Lave et al. 2007 ). But as with the more traditional in-house physiologically based pharmacokinetic (PBPK) whole body models (practiced over a longer period), there has been little development of the liver component from the standard models (described above). Beyond the extrapolation modeling issues, successful methodology for prediction of CL will ultimately depend on resolving the biological variability in vitro-inherent in drug transporter and drugmetabolizing activity-with that in vivo.
A major difficulty in identifying the general causes of underprediction of CL is the high degree of variance seen among a set of predictions  (Blanchard et al. 2006; Hallifax and Houston 2009). Inter-individual variability in expression of drug-metabolizing enzymes (and transporters) is anticipated from the known genotypes but subsequent modulation by various factors (hormonal status, diet, environmental chemicals, etc. ) leads to unpredictable phenotypes and hence problematical use of a population average  (Shah 2005). For several CYP substrates, CL ranged about fourfold between clinical subjects, whereas in vitro, CYP activities were found to range from 30-to 100-fold (depending on the CYP) for either microsomes or hepatocytes (in a database of commercially available material), indicating a wide inherent in vitro variation  (Hallifax and Houston 2009).
• Studies in primary liver cells will also allow for the future use of high-throughput screening methods that quickly and efficiently allow us to evaluate the risk from AhR ligands while eliminating the use of laboratory animals. • The availability of human cells to provide the data needed to reduce the current uncertainties that exist with PCDD/F risk assessments. Aryl hydrocarbon receptor (AhR) ligands, especially the persistent polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs), are human health concerns  (Denison et al. 2011; EPA 2012). Some non-persistent AhR ligands, on the other hand, are being assessed as potential pharmacological agents for treating cancer, allergy, asthma and inflammatory bowel disease (Esser 2012). In addition, a clear role for the AhR in normal biology is evidenced by abnormal organ/tissue development and function in AhR knockout mice, suggesting an important role for yet-to-be determined naturally occurring ligands(s)  (Gonzalez et al.