dataesr/scientific-paragraphs-categorization huggingface dataset:
High drug loading is now also known to be of importance as accelerated ADC clearance and reduction in exposure to conjugated auristatin appear to be consequential. Dr. Senter described the underlying cause of accelerated clearance as due to uptake in liver for overloaded drug (outside of hepatocytes). The type of conjugate employed must also be considered when generating ADCs, as evidenced by an example of hydrophobic conjugate localizing much more poorly in tumors than the naked antibody. Dr. Senter then focused his presentation on what lies ahead in the ADC field. Results from clinical trials with multiple agents were shared against a wide panel of malignancies. He discussed the example of brentuximab vedotin (Adcetris®) combined with standard frontline regimen in a Phase 1 study (ClinicalTrials.
gov NCT01060904). The regimen, which included doxorubicin, vinblastine, and dacarbazine with or without bleomycin, was combined with brentuximab vedotin for treatment of advanced stage Hodgkin lymphoma. 150 dditional improvements to current ADCs strategies at Seattle Genetics were also discussed. Pyrrolobenzodiazepines (PBDs) are a promising chemotype of ADCs under investigation as part of their partnership with Spirogen. These small molecules are very potent as DNA minor groove-binding molecules, and Dr. Senter reported that the linkage of PDBs via engineered cysteine in the CH2 region of the Fc improved stability over other methods. Seattle Genetics currently has an anti-CD33 ADC in Phase 1 that had previously showed improved activity in AML models as conjugated to PBDs over auristatin. Dr.
Dr. Reilly concluded by sharing the development plan for ABT-414. He spoke of the desperate need for new therapies in glioblastoma and noted there may be synergy among ABT-414 and the current standard of care treatment of radiation and temozolomide combination therapy. ABT-414 is currently being evaluated as a treatment for EGFR-refractory metastatic solid tumors (Phase 2 study NCT01741727), and glioblastoma (Phase 1 study NCT01800695). Dose-escalation is currently underway and early reports indicate no skin rash has been observed. Jagath R. Junutula (Genentech) discussed site-specific conjugation as a way to build next-generation ADCs with improved therapeutic indices. He began his presentation with a review of the function of ADCs  157  and the need for a balance between efficacy and toxicity.
Acknowledgements We thank the  Max Planck Society  and the  CNRS  for financial support. J. -C. B. and F. M. also acknowledge funding support from the  European Research Council (ERC)  under the European Unions  Seventh Framework Program  ( FP7/2007-2013) / ERC  grant no. 306385SofI. We thank  W. Keiderling ,  A. Gerke  and  W. Schubert  at the Workshop facility of the MPIds for technical support and  Max Planck Innovation GmbH  for helpful support. A patent application related to this system has been filed.
Numerical setup For the numerical examples we have implemented the model in the Mathematica package SARAH  [80] [81] [82] [83] [84] , which creates the required modules for SPheno  [85, 86]  to calculate the masses and mixing matrices including the complete 1-loop corrections. In the Higgs sector we include in addition the known 2-loop corrections to the Higgs mass from the MSSM  [114] [115] [116] [117] [118] [119]. However, this does not include 2-loop corrections stemming from the extended neutrino and sneutrino sectors, where we can have sizable Yukawa couplings. Moreover, SARAH calculates also the full 2-loop RGEs including the entire flavor structure for the model, which we have summarized in Appendix B. This will be of great importance in our numerical studies, as we use CMSSM-like boundary conditions, see below for their definition.
Acknowledgements We thank  Martin Hirsch  and  Ernesto Arganda  for fruitful discussions. A. V. acknowledges partial support from the  EXPL/FIS-NUC/0460/2013  project financed by the  Portuguese FCT. M. E. K. and W. P. have been supported by the  DFG , project no. PO-1337/3-1  and the DFG research training group GRK 1147. FS is supported by the  BMBF PT DESY Verbundprojekt 05H2013-THEORIE 'Vergleich von LHC-Daten mit supersymmetrischen Modellen '. C. W. receives financial support from the  Spanish CICYT  through the project  FPA2012-31880  and a partial support from the  European Union   FP7 ITN INVISIBLES (Marie Curie Actions ,  PITN-GA-2011-289442 ) and the  Spanish MINECO's "Centro de Excelencia Severo Ochoa" Programme  under grant  SEV-2012-0249. A. A acknowledges support from the  European Union   FP7 ITN INVISIBLES (Marie Curie Actions ,  PITN-GA-2011-289442 ).
G and F matrices are resolved for a minimum value of Q, defined as follows: Q = i j e 2 ij σ 2 ij , (2) where σ ij represents the measurement uncertainty of each data point. The analysis of ACSM organic mass spectra was performed using SourceFinder (SoFi v4. 5, http://www. psi. ch/ acsm-stations/me-2). This toolkit, implemented along with AMS and ACSM data processing software in Igor Pro (Wavemetrics, Inc. ), was recently developed by  Canonaco et al. (2013). It allows users to take advantage of the multilinear engine (ME-2) algorithm  (Paatero and Hopke, 2003) , where a priori information might be introduced in form of known factor profiles and/or factor time series into the PMF analysis  (Lanz et al. , 2008). In this study the a value technique of the ME-2 solver was employed, where the constrained factor profiles were allowed to vary within the scalar value "a" (Eq.
3). f j,solution = f j ± a • f j , (3) where f represents one factor profile in the F matrix. Time-series and uncertainty matrices were both obtained from the ACSM data analysis software (acsm_local Igor procedure v1520)  (Zhang et al. , 2005; Ng et al. , 2011; Ulbrich et al. , 2009). In our study, the two matrices contain 73 mass fragments (m/z), from m/z = 12 to m/z = 100, and 2040 samples. Previous AMS measurements performed in Paris  (Crippa et al. , 2013a, b)  offered the opportunity to implement a priori factor profiles specifically representative of the Ile-de-France wintertime pollution; HOA and BBOA factor profiles were retrieved from the AMS spectral database (http://cires. colorado. edu/jimenez-group/ AMSsd/,  Ulbrich et al. , 2009). The model was run several times, testing several numbers of (unconstrained) factors and a values, as presented in the Sects.
5•x 2 , -∞ < x < ∞ (6) K 2 (x) = 0. 75 • 1 -x 2 , -1 < x < 1 = 0 (7) Smoothing parameters σ and h can be calculated using Gaussian distribution equations (Full Width at Half Maximum),  but their empirical determination leads to similar results, since reasonable variations from their theoretical values do not change the final interpretation. Meteorological data used for NWR were obtained from continuous 1 min measurements carried out on the campus of the Polytechnic School (Ecole Polytechnique) (4 km east of the measurement site) with an A100R Campbell Scientific anemometer and a W200P Campbell Scientific weather vane at 25 m above ground level (a. g. l. ), above any impediment (e. g. , trees or buildings) that could affect the measurement of a particular wind sector.
Acknowledgements. The research leading to the these results has received funding from  INERIS , the  European Union   Seventh Framework Program  ( FP7/2007-2013 ) project  ACTRIS  under grant agreement no. 262254 , the  DIM-R2DS program  for the funding of the ACSM equipment, the  PRIMEQUAL PREQUALIF program  for long-term observations of  Black Carbon. Edited by:  N. Mihalopoulos.
Longer reads consisting of 502100 nt provided little additional benefits on the U regions extent. Second, to analyze the remaining multialigned (M) regions, we identified the intragenomic single-nucleotide variants and thus defined the unique (M U ) and multialigned (M M ) subregions, as exemplified for the polymorphic copies of the six flocculation genes and the 50 Ty retrotransposons. As a resource, the coordinates of the U and M regions of the yeast genome have been added to the Saccharomyces Genome Database (www. yeastgenome. org). The benefit of this advanced method of genome annotation was confirmed by our ability to identify acquired single nucleotide polymorphisms in the U and M regions of an experimentally sequenced variant wild-type yeast strain.
Repeated sequences lead to the production of identical or slightly polymorphic reads that originate from different chromosomal locations. Robust analyses therefore depend on how efficiently one can minimize the confusing effects that multialignments pose. The most intuitive strategy is based on the selection of the "best" alignment among multialignments according to the number of mismatches. Short Oligonucleotide Alignment Program (SOAP)  (Li et al. 2008b)  and Program to Align Short Sequences (PASS)  (Campagna et al. 2009 ) programs implement such strategies in which the "best" alignment is defined as the one with the smallest number of mismatches. A second approach is implemented in a program MApping short reads and calling variants using mapping Quality score MAQ  (Li et al. 2008a)  uses the notion of "mappability.
Operationally, it reduces FP calls but finally restricts the analysis to highly "mappable" regions. Here, we report two generic and complementary bioinformatics strategies based on advanced annotations of the reference genome. As a proof of concept, it allowed us to (i) deconvolute the Saccharomyces cerevisiae genome into unique (U) and multialigned (M) regions using virtual read analyses, (ii) establish a list of the intragenomic SNVs that characterize whole-genome repetitiveness (provided as a resource in the Saccharomyces Genome Database [SGD] database; http://www. yeastgenome. org/), and (iii) explore the M regions to define subsets of unique regions (M U ) and identify M region distinguishing variants. The alignment filter we developed, "g-deNoise," anticipates the impact of intragenomic SNVs in multialignments.
Reads mapping The simulated dinucleotide color space reads were back aligned against the S. cerevisiae reference genome using the "mapreads" program from Applied Biosystems SOLiD "corona lite 4. 2. 2" software package. Our standard mapping parameters were set to allow six mismatches per 50 nt-read alignment. To generate an exhaustive mapping result, no threshold was fixed to limit the number of reported alignments per read. It is noteworthy that six mismatches in color-space are not equivalent to six mismatches in base-space  (Breu 2008 ). In the base-space simulation experiments, the virtual reads were aligned on the reference sequence with the software BFAST  (Homer et al. 2009). Only alignments without gaps and containing at most three base mismatches were considered. No threshold was fixed to limit the number of alignments reported per read.
Robustness of the M regions according to the method of virtual read production To compare reads generated with different sequencing technologies, we also performed the HTS simulation by generating virtual reads in base space (for example as in Illumina sequencing) rather than color space (like in SOLiD sequencing). Using fixed parameters, 50 nt-reads and a maximal number of three mismatches in base space (equivalent to six mismatches in color space), the percentage of genome covered by M regions, after mapping with the BFAST software, was slightly lower than in color space (6. 55% vs. 8. 4%). The M regions identified in base space simulation are included in the M regions identified in color space. The additional M-specific regions identified with color space simulation are due to the enhanced calls in low complexity sequences and exquisitely discriminate the Ty regions (see peaks at 526 kb in Figure  2B  compared with Figure  2D ).
The usage of mate-paired libraries with larger inserts between the reads or extra-long single molecule read technologies  (Sharon et al. 2013 ) associated with powerful de novo assembly software will be necessary to be exhaustive. Our analysis of the S. cerevisiae genome is a resource of general interest available at SGD. This resource will have multiple benefits: (i) to define the U and M regions, (ii) to provide a simple and global U/M readout of the genome complexity that can be used to compare variant strains and species, (iii) to allow precise measurements of HTS coverage by using the set of U regions as the reference genome ploidy index to count experimental reads, and (iv) to facilitate the identification of constitutive and acquired mutations in both unique and highly repetitive regions of variant strains.
ACKNOWLEDGMENTS We thank  Allyson Holmes  for her critical reading of the manuscript. This work was funded by the  "Agence Nationale pour la Recherche , " grant  " MUTome " # ANR-09-BLAN-0278-01  to A. N. The  IC-NGS  platform received financial support from the  ANR  (investissements d'avenir  ANR-10-EQPX-03  and  ANR-INBS-09-08 ), the  Cancéropôle Ile de France , the  Région Ile de France , and  France Génomique. C. J. received a doctoral grant from the " Fondation ARC Pour La Recherche Sur Le Cancer " and from the  "Cellule d'enseignement de l'Institut Curie. ".
Current codes and data Several Boltzmann codes have been made public and compared with each other, including cmbfast,  [2] [3] [4] , implementing for the first time the line-of-sight method, and later camb  [5] , cmbeasy  [6]  and class  [7, 8]. Both camb and class are being maintained and pushed to ever higher precision, and both were used in different parts of the Planck data analysis. All current cosmological data can be well fitted with a flat FLRW model. Still, it is important to have efficient Boltzmann codes which also cover non-flat models, in order to check for small deviations from spatial flatness in future data. Currently, the bounds read 100Ω k = -1 +1. 8  -1. 9 at the 95% confidence level using Planck alone and 100Ω k = -0. 10 +0. 62 -0. 65 when combining Planck with BAO  [9].
Establishing a reference method The first step in building the hyperspherical Bessel module was to find a reliable reference implementation to which we could compare our methods. From equation (2. 3) we see that they are given in terms of Legendre functions and also hypergeometric functions using wellknown identites. But no general and stable numerical algorithm exist for the computation of Legendre functions or hypergeometric functions of large order, not even in commercial software. So for establishing a set of trusted methods, we implemented many different methods in MATLAB. Whenever possible we coded the routines such that they would work also for K = 0: the first check would then be to test the routine against MATLAB's built-in Bessel function routine which is known to be precise. We implemented the following 5 schemes in MATLAB: 1.
For a reliable comparison, we switched off OpenMP, and compiled the codes with recent versions of gcc or gfortran, using exactly the same optimisation flags, and running on the same processor. These times are expressed in seconds, but they are only useful for the sake of comparison: on modern processors with many cores the execution time will of course be much smaller. In figure  5. 4, we show the ratio of temperature and polarisation spectra computed for Ω k = ±10 -5 compared to the class reference spectra for Ω k = 0. We expect the true difference between the spectra to be also of the order 10 -5. The precision settings to be used in a parameter extraction code should be such that these models do not differ by more than 0. 1%, meaning that they could not be discriminated from each other, given the accuracy of current CMB data.
Also, American colleges and universities started to develop "researcher-centric" models of institutional repositories, with roots lying "in the open access publishing movement within libraries"  (Younglove 2013). These repositories are designed as a platform for researchers to collaborate with one another, store data sets, and publish their research through the library, and they can be linked to or are even part of research systems. Younglove cites two universities that made their repositories become more like CRIS systems, the Harvard repository DASH and Indiana University's OJS. But again, there is no specific information about theses. Yet, the challenge of this topic has been identified and addressed elsewhere. Sachini et al. (2010)  describe the emerging Greek ETD infrastructure including an ETD repository and insist on the CRIS connection with structured information about authors, organisations as well as research projects which have specifically funded PhD theses.
They list 13 metadata about theses and dissertations with their storing method in the CERIF data model, as a link, entity or attribute (author, title, subtitle, keywords, abstract, note, ISBN, total pages, publisher, publication date, URI, thesis type, institution). They also describe their own CRIS-UNS data model based on CERIF but more exhaustive insofar it integrates 18 additional elements from the library MARC 21 records, for instance advisor, chair, committee member, access rights, name of degree, scientific discipline or date of defense (see  Ivanovic et al. 2012a, tables I and V). The Novi Sad project demonstrates the flexibility and adaptability of CERIF for the specific needs of ETD. Yet, all MARC 21 or ETD-MS metadata may not be necessary for research evaluation (such as extended abstract, physical description or even content format).
The CRTD, together with selected internet resources serve as a comparative corpus for the system for plagiarism detection, called also the Antiplagiarism System (APS). Once the work is checked for plagiarism, an output protocol is produced for each work, which serves the exam commission as a tool for deciding about the work originality  (Noge 2011). The system has been running since 2009. Its database comprises graduation publications (bachelor, diploma and doctoral) and qualification postdoctoral publications of academic members of all Slovak universities from 2010. The CRTD contains almost 300,000 documents. Expected increase counts around 75,000 documents per year  (Noge & Dušková 2013). All documents sent to the register since September 2011 are also published on the crzp. sk portal. Presentation of works to the public depends on the parameters of the license agreement and may include metadata or full text.
The CRTD metadata structure follows principles of UNIMARC format. SOAP Web service offering the metadata in MARC XML. The xsd schema contains a description of several entities used in CERIF. Organisation means university and its basic part (faculty, institute) guaranteeing relevant study programme. They are registered in three levels: University -Faculty -Department. For instance, TNFPTKMTaE means: TN -Alexander Dubček University in Trenčín, FPT-Faculty of Industrial Technologies in Púchov and KMTaE -Department of Material Technology and Environment Person in ETD has defined following fields: Name, Surname, Affiliation Pers_OrgUnit. Person could also play multiple roles in relation to ETD work: adviser, supervisor, reviewer, opponent, consultant, author. These roles are compatible with CERIF semantics categories.
SEMAT, the Iranian national CRIS, is managing research information across all institutions in Iran. On the other hand, CSTIS, a policy making and standard establishing body, is developing standards for metadata management of all research objects in SEMAT and also is responsible to assign national level projects to Iranian institutes  (Mehrtash & Fatemi 2012). The new national ETD repository which stores every ETD along with its full text addresses all the issues mentioned above. All data are registered and managed during the work flow of every individual object in a central registration system. The idea is to register and collect related data of the ETD during the typical workflow of initiating a thesis/dissertation, approval of the proposal and defending the work as illustrated in Fig. 1.
All institutions (including universities and research institutes) are required by CSTIS to setup registration services for every thesis. The GANJ registration system communicates with their online submitting system, once the thesis receives acceptance. The minimum requirement for GANJ to accept registration of the thesis is: "successful defense". In these points, which are shown by flags in Fig. 1 , metadata and full text are being registered in GANJ and thus the scientific information becomes retrievable for researchers. This infrastructure satisfies major quality criteria: • Interoperability: Every IR system with its own workflow sends the data to both SEMAT and GANJ. The initiation of each transfer is by the originating system (i. e. IR). • Completeness: Since every individual thesis is going through the institute workflow, we can be sure about the completeness of the repository.
As described before, SEMAT (Iranian national CRIS) is integrating metadata of all research entities. On the other hand, GANJ is responsible to integrate all data related to theses and dissertations including full-texts and metadata. In addition to these two national systems, there are also the institutional repositories or research information systems of every individual institution. The interoperability among these systems is explained below. There are lots of systems including research systems and non-research systems which involve in research information as shown in Fig. 2. For example, human resource system as a non-research system of an institution is holding the information of researchers. This "enterprise bus system" design acts as the national research hub where every system is physically connected to this bus through Internet as shown by solid lines in Fig.
3. By having the physical connection between every system and the hub, the logical connections between any two systems is feasible as shown by dotted lines in Fig. 3. Therefore any message generated in the ETD system of an institute is delivered to both GANJ and SEMAT through this hub. The metadata of the article is stored in SEMAT database while the full information including the full-text is stored in GANJ. Once the physical and logical connections established, all systems need to communicate. Such a distributed environment introduces many issues like latency, synchronization and partial failure of one system. A loose coupling using message passing mechanisms has been preferred, with messaging protocols based on xml. Each message is issued by an authorized issuing system which is the origin of the data.
Metadata Metadata on PhD theses are produced in different formats and with different degrees of richness and complexity. Basic elements are: author, title, institution, date, advisor, key words. This may be enough for retrieval in repositories but it is not sufficient for CRIS. At least three aspects must be taken into account: Standards: ETD metadata should be produced and disseminated in a standard format and not in a format specific to an institution or network, in order to facilitate the integration and exploitation by a CRIS. The minimum standard is the Dublin Core. Richness: PhD theses contain more information about research than minimal metadata often represent. In order to enhance research evaluation by CRIS, ETD metadata could or should include the following elements: author with affiliation, validating institution (university) with full details (town, region, country, type), hosting institution e.