dataesr/scientific-paragraphs-categorization huggingface dataset:
Binary Segmentation, a fast heuristic  Olshen et al. [2004]  and Pruned Exact Linear Time (PELT),  Killick et al. [2012]  an exact algorithm for optimal segmentation with respect to the likelihood, are both implemented for the Poisson distribution in package changepoint. Even though both are extremely fast, do not require a comparison profile and analyse count-data, the Poisson distribution is in-adapted to our kind of data-sets. A recent study of Hocking has compared 13 segmentation methods for the analysis of chromosomal copy number profiles and has shown the excellent performances of the Pruned Dynamic Programming (PDP) algorithm proposed by  Rigaill [2010]  in its initial implementation for the analysis of Gaussian data in the R package cghseg. We propose to use the PDP algorithm which we have implemented for the Poisson and negative binomial distributions.
R package The Pruned Dynamic Programming algorithm is available in the function Segmentor of the R package Segmentor3IsBack. The user can choose the distribution with the slot model (1 for Poisson, 2 for Gaussian homoscedastic, 3 for negative binomial and 4 for segmentation of the variance). It returns an S4 object of class Segmentor which can later be processed for other purposes. The function SelectModel provides four criteria for choosing the optimal number of segments: AIC  Akaike [1974] ,  BIC Yao [1984] , the modified BIC  Zhang and Siegmund [2007]  (available for Gaussian and Poisson distribution) and oracle penalties (available for the Gaussian distribution  Lebarbier [2005]  and for the Poisson and negative binomial Cleynen and  Lebarbier [2013]  as described previously). This latter kind of penalties require tuning a constant according to the data, which is done using the slope heuristic  Arlot and Massart [2009].
Yeast RNAseq experiment We applied our algorithm to the segmentation of chromosome 1 of the S. Cerevisiae (yeast) using RNA-Seq data from the Sherlock Laboratory at Stanford University  Risso et al. [2011]  and publicly available from the NCBI's Sequence Read Archive (SRA, http://www. ncbi. nlm. nih. gov/sra, accession number SRA048710). We selected the number of segments using our oracle penalty described in the previous section. An existing annotation is available on the Saccharomyces Genome Database (SGD) at http: //www. yeastgenome. org, which allows us to validate our results. With a run-time of 25 minutes (for a signal length of 230218), we selected 103 segments with the negative q q q q q q q q q q 0e+00 2e+05 4e+05 6e+05 8e+05 1e+06 0 10 20 30 40 signal size time/Kmax (s) q q q q q q q q q q q q q q q q q q q q q q q q q q q q q q phi=0.
Cloud-based services have become a norm for business application development. With Cloud Computing and the convergence toward Everything as a Service (XaaS), we no longer consider the classical context of application development, where IT teams or integrators are solicited. Current approaches in Cloud environments are usually designed for a specific Cloud platform; moreover, they are only designed for technical users. To overcome the lack of generic and complete methodology for business application development, we propose a methodology for Automatic Software Development as a Service (ASDaaS), which is designed for non-technical users and promotes services reuse. In this paper, we focus on the phase of business software requirement gathering of our methodology. We define the requirement vocabulary based on linked data principles, and extend the Linked-USDL language to describe business stakeholder requirements as service functions, business constraints, user preferences and QoS parameters.
There is a need for a model that provides explicit description of requirements to ensure then the correct selection of services, and (iii) how to adapt or extend service description languages to facilitate services selection that meet user's requirements. In this paper, we propose a methodology for business application development for Cloud environments allowing business stakeholders to perform the automatic development of those applications. This methodology is called Automatic Software Development as a Service (ASDaaS) and promotes the discovery and the composition of Cloud services that match functional and non-functional business application requirements. Functional requirements describe service features and business constraints. Non-functional requirements describe user preferences and Quality of Service (QoS) parameters.
The originality of our work presented in this paper lies in the business application requirement description phase of the methodology. We define the requirement vocabulary based on the linked data principles (http://www. linkeddata. org/), and extend the Linked USDL language (http://www. linked-usdl. org/) so that it can describe business stakeholder's requirements as service functions, business constraints, user preferences and QoS parameters. The rest of this paper is organised as follows. Section 2 describes the works related to existing Cloud software development methodologies. Section 3 presents the proposed ASDaaS methodology. Section 4 introduces ASDaaS's architecture. We describe the implementation and evaluate our work in section 5. Section 6 draws final conclusions and describes our future work.
AUTOMATIC SOFTWARE DEVELOPMENT AS A SERVICE METHODOLOGY (ASDaaS) Our methodology for Automatic Software Development as a Service (ASDaaS) is aimed at business stakeholders who need a business application to automate a frequent task. In this section, we describe the ASDaaS methodology through the described scenario. The originality of our approach lies in the following: (i) it allows selection of a development platform (PaaS) according to user preferences and restrictions of available Cloud services, such as suitable APIs, and (ii) it allows selection of IaaS for deployment that meets the predefined user preferences and QoS parameters. These phases are explained in the next sections. In this paper we focus on business application requirement expression, i. e. the initial phase of the ASDaaS methodology.
• Business constraints: -Purchase cost max value = 1000 Euros. • QoS parameters: in order to describe its priorities regarding QoS parameters, he/she should assign coefficients to QoS parameters so that the sum of all the coefficients does not exceed 10. As business application integrates online payment, the stakeholder prefers to value data privacy and integrity more than service response time with the following coefficients: -Data privacy: 3, -Data integrity: 3, -Availability: 3, -Response time: 1. • Stakeholder preferences: -Services location: Europe, -Currency: Euro, -Cost max value: 500, -Preferred deployment provider: "Amazon", -Preferred provider for the purchase service: "Paypal". The existing USDL modules (https://github. com/linked-usdl. ) are not sufficient to describe non-functional aspects of stakeholder business requirements, such as the preference for invoking a business provider rather than another.
To achieve the goal of providing a unified language to describe business application requirements, we propose to extend the Linked USDL language by defining a "USDL-requirement" vocabulary, which will allow matching the business application requirements with the Linked USDL Cloud service descriptions. Multiple vocabularies exist (http://lov. okfn. org/dataset/lov/); we will reuse some of their classes and properties following linked data principles. The USDL-requirement vocabulary describes business application requirements in terms of stakeholder preferences, QoS parameters, service functions, and business constraints. Figure  2  illustrates classes and properties that we define in the USDL-requirement vocabulary. Rectangles represent classes, and the circles represent the properties. For example, the property 7 illustrates that a requirement comprises functions, and the property 8 shows that the stakeholder can define his preferred provider for a given function.
IMPLEMENTATION & VALIDATION In order to validate and evaluate our proposal, we are implementing a prototype for ASDaaS using Java language. The phases of requirements expression, services discovery and IaaS selection are implemented. We use the Apache Jena Library for modeling and manipulating the USDL files and the SPARQL Query Language for querying them. We have implemented an IT history service that is responsible for returning the QoS parameters values for each discovered service. Due to the early stage of implementation, few tests have been done. We have evaluated the service discovery execution time variation with the number of services in the marketplace. Figure  5  depicts these results obtained for the service discovery phase for our running scenario.
CONCLUSIONS With Cloud computing, the application development is changing, providing environments enabling to empower business stakeholders and to automatize the software development activities. In this paper, we have described a methodology for Cloud-based collaborative software development, and then presented the ASDaaS architecture that addresses the challenges of interoperability, independency to a specific platform, and respects the distributed nature of the Cloud environment. ASDaaS generates a business application based on discovered and developed on-the-fly business Cloud services. Currently we are implementing the business Cloud service composition module. In the future, we will deploy the ASDaaS architecture in the Cloud Platform of the Lyon 1 University for evaluating and testing this work with a large set of cloud services.
Scope of the survey At the outset, the research team identified literature associated with the subject matter based on searches in PubMed, the Institute of Electrical and Electronics Engineers (IEEE), Science Direct and Google Scholar databases using various combinations of the following keywords: upper extremity, arm, hand, rehabilitation, therapy, training, movement, motion, assistance, support, robot, robotized, robotic, mechatronic, and motorized. Additionally, referenced literature from the selected publications was included in the survey as well. The information obtained from this literature compendium is supplemented with the data acquired from professional caregivers and manufacturers' catalogs and websites, as well as direct communications with rehabilitation professionals, manufacturers and patients.
It also allows for using the device as an assessment tool to measure patient's range of motion. The majority of the devices presented in Table  1  allow movements in three dimensions; however there are also planar robots, i. e. , systems allowing movements only on a specified plane (e. g. MEMOS  [132]  and PLEMO  [105] ). Also the MIT Manus system initially allowed movements only on one plane  [107]. Subsequently, an anti-gravity module added possibility to perform vertical movements  [133]  (Figure  1B ). Designing the device as a planar robot reduces the range of movements that can be exercised for particular joint. It also reduces the cost of the device. Furthermore, when the working plane is well selected, the range of training motion may suffice in most of therapeutic scenarios. Some of such planar devices allow changes in the working space between horizontal and vertical (Braccio di Ferro  [134] ) or even almost freely selecting the working plane (e.
The actuators can be placed distally, close to the joints on which they actuate (e. g. ArmeoPower system, Figure  1D ). This specification simplifies the power transmission by using direct drives. However, it increases the weight of the distal part of the device and inertia and makes it more difficult to control the system. On the other hand, locating the actuators in the proximal part of the device, often in the part that remains constrained, reduces the weight and inertia of the distal part. However, a power transmission mechanism complicates the mechanical structure and may lead to difficulties with control due to friction. For example, the same group who developed InMotion HAND http://www. jneuroengrehab. com/content/11/1/3 system proposed an earlier prototype of the hand module with eight active DOF and cable-driven mechanism for power transmission.
Similar to category II, however, usually these are multicentered studies with high number of participants. that provides a therapy protocol rather than an end product  [198] , thus they are rather interested in responses to questions concerning optimal training intensity, disorders for which such form of training may be beneficial, and whether robotic therapy should substitute or complement other forms of therapy. This survey includes a search into the US Clinical Trials database (http://clinicaltrials. gov/) from October 2013 using a combination of keywords: robotic, robot, therapy and rehabilitation. This is an web-based database existing since 1997 and maintained by the US National Library of Medicine at the National Institutes of Health. Under the American Food and Drug Administration Amendments Act (FDAAA) of 2007 all the applicable clinical trials (what concerns category II and III/IV studies in our survey) performed in the USA and starting after 2007 have to be registered in this database.
Acknowledgements We would like to thank  Mrs. Christine Azevedo-Coste, Ph. D. for her critical reading and revising the manuscript and  Mr. Gabriel David Nevarez ,  P. E. for proofreading the English. The work of PM has been supported by the  European Union  in the framework of  European Social Fund  through the  Warsaw University of Technology Development Program. He would also like to thank the  Center for Advanced Studies of the Warsaw University of Technology  for the support that he received during preparation of this work and the Chair of Medical Engineering (mediTEC),  Helmholtz-Institute for Biomedical Engineering, RWTH Aachen University  for the possibility of performing the majority of the work on this manuscript during scientific stay in that institution.
Introduction The early detection of tuberculosis (TB) outbreaks, particularly those involving multidrug-resistant (MDR) or extensively drugresistant (XDR) Mycobacterium tuberculosis strains, is critical to prevent further expansion to the wider community. 1, 2 7] [8] [9]  IS6110 RFLP has long been considered the gold standard for discriminating M. tuberculosis complex (MTBC) strains. 6, 10 It has proved instrumental in detecting outbreaks, reactivation, and laboratory contaminations. Unfortunately, as a hybridization-based method, IS6110 RFLP requires large amounts of DNA and is labor-intensive and time-consuming. In addition, IS6110 RFLP cannot efficiently discriminate strains with low IS6110 copy numbers (less than five copies). 11, 12 Another major drawback of IS6110 RFLP is the fact that the resulting fingerprinting profiles are not suitable for data banking or inter-laboratory comparisons.
2. 3. Automated fragment size fractionation of IS6110-5 0 3 0 FP generated products IS6110-5 0 3 0 FP products were diluted 1/20, and 1 ml of the dilution was mixed with 0. 5 ml of GeneScan 1200 LIZ and 9 ml of Hi-Di Formamide. The mix was denatured for 2 min at 95 8C. Automated fragment analysis was performed using LIZ 1200 as a DNA size marker on an ABI PRISM 3100 capillary DNA sequencer (Applied Biosystems Inc. , CA, USA). The electrophoresis was done using POP-7 Polymer and a 50-cm length capillary. Electrophoresis parameters were set according to the 3130_50cm_POP-7_GS1200LIZ run module (Applied Biosystems Inc. , CA, USA).
Data analysis Chromatographs showing FAM-and JOE-fluorescing fragments were imported into GeneMapper software v. 4 (Applied Biosystems) and analyzed using amplified fragment length polymorphism (AFLP) default and the advanced mode with selection of a starting point of electrophoresis at 3250 data point. The threshold for assigning a peak was set to 200 relative fluorescence units (RFU), based on preliminary experiments using a negative control (IS6110-5 0 3 0 FP auto-ligation product), whose fluorescence peaks were reduced to less than 50 RFU at the 1/20 dilution. The size of fragments was determined using GeneScan 1200 LIZ v. 2 (Applied Biosystems) with a sizing quality >0. 95, and verified using the plot determined by the software. GeneMapper also recorded the fragment data in binary format in Excel files, which were exported into BioNumerics v.
eGFP fluorescence peaked at 6 weeks postinjection (data not shown) and remained stable for at least 9 mpi, the time when the animals were sacrificed for histological assessment (Figure  1c ). Histological sections were performed in the vector-exposed area. Epifluorescence microscopy showed eGFP expression limited to photoreceptor cells (cell bodies, inner/outer segments) (Figure  1d ). Notably, a robust transduction of cones was detected (Figure  1f-h ). Cones were identified based on two criteria: their well-defined shape and their labeling with L/M opsin (Figure  1e-h ), a known marker of L/M cone outer segments, and at high exposure, of L/M cone inner segments (Figure  1h ). Recombinant AAV2/5-RK-eGFP transduced on average 49 ± 21% of L/M cones (number of double-labeled eGFP/opsin cones per field at ×20 magnification, n = 2 eyes).
Morphology of long-term preserved photoreceptors in MLHD-Cord1 treated eyes. To further determine which subtypes of photoreceptors were maintained in transduced area of MLHD-Cord1 treated eye, dog A2 was sacrificed at 24 mpi, and its retinas were analyzed by histology. Retina cryo-sections containing the vector-exposed region in the temporal half of the section and vector-unexposed regions in the nasal half were stained with eosin/hematoxylin (Figure  4b ) or labeled against rod-(GNAT1) and cone-specific markers (peanut lectin agglutinin (PNA), L/M opsin, and S opsin) (Figure  4c  and Supplementary Figure  S3b ). None of the four tested antibodies raised against the murine or human Rpgrip1 antigens showed specific staining on canine retinal flat mounts, cryo-or paraffin-embedded sections (data not shown).
PCR amplification was performed using KOD Hot Start Polymerase (Novagen, Merck Eurolab, Fontenay sous Bois, France) under the following conditions: initiation at 95°C for 2 minutes, followed by 35 cycles of denaturation, annealing, and extension (depending on the amplicon; Supplementary Table  S1 ). PCR products were then analyzed on a 1. 5% agarose gel, extracted (NucleoSpin Extract II kit, Macherey Nagel, Hoerdt, France), cloned into the pS972 vector (Promega, Charbonnières, France), and sequenced with standard SP6 and T7 forward and reverse primers. Rpgrip1-1 to Rpgrip1-7 PCR fragments were assembled using endogenous restriction sites present in the cRpgrip1 cDNA. The cloned cRpgrip1 cDNA was verified by sequencing and was identical to the recently published canine Rpgrip1 reference sequence (GenBank HM021768).
In vivo GFP fluorescence imaging and GFP expression analysis. GFP fluorescence in dogs NA2 and NA3 was monitored at weekly intervals by fluorescence retinal imaging using a Canon UVI retinal camera connected to a digital imaging system (Lhedioph Win Software, Lheritier SA, Saint-Ouen-l' Aumône, France). At 9 mpi, dogs were euthanized by intravenous injection of pentobarbital sodium (Vétoquinol, Lure, France). Eyecups were fixed for 48 hours in Bouin's solution (Laurylab, Saint Fons, France), embedded in paraffin, and 7-µm sections were prepared. Before immunostaining, sections were deparaffinized in toluene and rehydrated with phosphate-buffered saline solution. This method allows good preservation of cone photoreceptor shape but slightly reduces eGFP fluorescence. Nonspecific antigen binding was blocked by incubating sections in blocking solution (20% normal goat serum (Invitrogen), 0.
A P value <0. 05 was considered significant (confidence intervals = 95%). Statistical analyzes were performed using GraphPad Prism for Macintosh (GraphPad, Software, San Diego, CA). Spectral-domain OCT. SD-OCT was performed bilaterally on dogs A2, A7, and A8 at 24 mpi. Pupils were dilated as described above, and dogs were anesthetized following premedication by intravenous injection of thiopental sodium (Specia Laboratories, Paris, France) followed by isoflurane gas inhalation. SD-OCT was performed with 30° horizontal scans placed across the vector bleb temporal boundary (Spectralis Heidelberg Engineering, Heidelberg, Germany). Scans covered retinal regions of 13 × 8 mm (13 line scans of 1 × 8 mm, 23 averaging). Postacquisition processing of OCT data was performed with a commercial program following manufacturer's instructions (Heidelberg).
29 Mann-Whitney paired t-test was used to statistically analyze the results from treated and untreated eyes. A P value <0. 05 was considered significant (confidence intervals = 95%). Statistical analyzes were performed using GraphPad Prism for Macintosh (GraphPad Software). Behavioral studies. Ambulation of treated Rpgrip1 -/-dogs through an obstacle avoidance course in bright-(260 ± 13 lux) and dim-light (1. 5 ± 0. 8 lux) conditions was evaluated at 4, 9, 12, 18, and 24 mpi as previously described. 10 An opaque lens was used to alternatively cover the treated or the untreated eye, and obstacle panel combinations were randomly determined for each test to prevent the dogs memorizing the positions of the obstacle panels. All dim-light films were cleared before mounting with commercial Final Cut Pro 7 software (Apple, Cork, Molecular Therapy vol.
ACKNOWLEDGMENTS We thank  Cathryn Mellersh  ( Animal Health Trust, Newmarket, Suffolk, UK ) for the gift of the first MLHD-Cord1 dogs and  Shahrokh Khani  ( State University of New-York, Buffalo, NY, USA ) for the gift of the human RK promoter. We thank the Vector Core (www. vectors. univ-nantes. fr)for production of the rAAV vectors, the staff of the  Boisbonne Center  and  Thibaut Larcher  ( INRA/ONIRIS, Nantes, France ) for animal care, and  Mireille Ledevin  ( INRA/ONIRIS, Nantes, France ) for technical assistance. We also thank  Knut Stieger  ( Justut-Liebig-University Giessen, Germany ) for critical reading of the manuscript. This work was supported by unrestricted grants from the  Association Française contre les Myopathies , the  INSERM , the  Fondation pour la Thérapie Génique en Pays de la Loire , and the  Agence Nationale pour la Recherche.
These results show that in myeloma patients resistant to velcade, the direct implication of a proteasome defect remains to be established. In our models velcade resistant U266 MM clones we failed to observe mutations or overexpression of the PSMB5 core leading to an increased chymotryptic activity. Moreover, no mutations or overexpression of the PSMB6 or PSMB7 proteasome subunits that could explain a reinforced caspase-like and trypsin-like activities, were detected (Supplemental 3 and data not shown). Using synthetic fluorescent substrates, we also measured the caspase-like, chymotrypsin-like and trypsinlike proteolytic activities in either U266 or R6 cells or in the corresponding cell lysates incubated or not with velcade. We demonstrated that both U266 and R6 clones exhibited similar basal chymotrypsin-like and caspaselike proteasome activities that were both sensitive to inhibition by velcade.
Microarrays experiment Microarray analyses were performed on the GeneChip Human Gene 1. 0 ST Array (Affymetrix, Santa Clara, CA 95051, USA), according to the manufacturer's instructions. RNA from each of the 3 cell population were labeled and hybridized. The experimental data will be deposited in the NCBI Gene Expression Omnibus (GEO) (http:// www. ncbi. nlm. nih. gov/geo/). Normalization of microarray data was performed using the Limma package available from Bioconductor (http://www. bioconductor. org). using the RMA method and means of ratios from velcade-resistant cells versus U266 parental cells were www. impactjournals. com/oncotarget calculated.