dataesr/scientific-paragraphs-categorization huggingface dataset:
Identification of Fifty-Eight Proteins Differentially Expressed with Aging by Proteomic Analysis. In order to obtain a quantitative proteomic map of elderly and young donor-derived keratinocyte cells, we used an iTRAQ labeling coupled with OFFGEL fractionation and off-line nanoLC/ MS/MS as previously described  [24]. The bioinformatics analysis with Paragon and Mascot search engines resulted in the identification of 517 unique proteins using a 1% FDR and considering only proteins with at least 1 peptide with confidence level ≥ 95% and score > 30. We performed a statistical analysis with the isobar package and quantified 446 proteins. Elderly keratinocytes were labeled with iTRAQ m/z 117 tag and young keratinocytes with iTRAQ m/z 113 tag. Thus, the ratio 117 : 113 (Elderly : Young) indicates the relative protein abundance between elderly and young cell samples.
The complete list of identified proteins, including the UniProtKB accession number, ID, protein and gene name, peptide count, spectral count, sequence coverage, iTRAQ ratios with corresponding p value ratio and p value sample for elderly versus young cells are provided in Supplemental Data (Table  S2 ). When the p value ratio and the p value sample were both <0. 05, proteins were considered significantly differently expressed. Applying these criteria, we identified 58 proteins significantly differentially expressed depending on age status. From them, 40 were downregulated and 18 were upregulated with aging (Tables  1  and 2 ).
We took advantage of available genomic data (GSE49598) comparing mRNA expression profiles of WT vs ATF4 À/À MEFs treated with the ER stress-inducer tunicamycin to define the core of an ATF4-dependent gene expression signature (Appendix Table  S2 ). Gene set enrichment analysis (GSEA)  (Subramanian et al, 2005) , which allows statistical assessment of changes in the expression of a predefined set of genes in different conditions, indicated that ATF4-dependent transcription was significantly increased (FDR < 0. 1) in WT cells stimulated with poly(I:C) compared with non-treated cells  (Fig 1E) ; however, this was not the case in activated GADD34   (Claudio et al, 2013; Fig 2A).
Flow cytometry Cells were fixed and permeabilized with cytofix/cytoperm buffer (BD Biosciences) for 15 min at 4°C and washed with perm/wash buffer (BD Biosciences) before antibody staining at 4°C. The antibodies used to detect GADD34 and p-eIF2a[Ser52] were identical to the ones used for immunoblotting. The secondary antibody used was conjugated to R-PE (Invitrogen). Intracellular IFN-b was detected with a FITC-conjugated monoclonal antibody (RMMB-1, PBL InterferonSource). Addition of brefeldin A (10 lg/ml) was necessary to detect IFN-b after HMW poly(I:C) treatment. Data were acquired on a Canto II (BD) and analyzed using FlowJo (Tree Star). For phospho-TBK1, phosflow cytofix and phosflow perm/wash were used (BD) to fix and permeabilize cells as indicated by manufacturers. Phospho-TBK1 (Ser172) was detected using a PE (directly)conjugated rabbit mAb (D52C2).
Stress granules detection and scoring Stress granules detection was performed by mosaic image acquisition of 49 planes with an Axio Observer. Z1 (Carl Zeiss) equipped with the software Zen 2 and a ORCA flash 4 camera. SGs were detected using an antibody recognizing G3BP1 (Millipore) and secondary antibody conjugated to Alexa 488. Nuclei were stained with DAPI. The fluorescence of the two channels was captured through the objective Plan Apochromat 40×/0. 95 and the fluorescence filters DAPI (BP 445/50) and GFP (BP525/50). The images were then processed individually with a homemade pipeline using ). Note that our goal was not to implement a biologically accurate model but to show that a certain type of behavior extended to a cell population can allow obtaining phenomena like those observed experimentally.
Acknowledgements A. D. and the laboratory received financial support from the  Innate Immunocytes in Health and Disease  ( I2HD ) Collaborative Project between CIML, AVIESAN, and SANOFI. TPVM was funded by the  European Research Council  under the European Community's  Seventh Framework Programme  (FP7/ 2007-2013 Grant Agreement number  281225  to MD for the  SystemsDendritic  project). AC received a MNERT and  ARC PhD fellowship. The laboratory is "Equipe de la Fondation de la Recherche Médicale" (FRM)  sponsored by the grant  DEQ20140329536. The project was supported by  Agence Nationale de la Recherche (ANR)  grants " ANR   10-BLAN-1236 ", " ANR 10-BLAN-1308 ", " ANR-12-BSV2-0025-01 ", " ANR-12-ISV3-0002 ". This work has also been carried out with the support of A* MIDEX-AAP-INME-1401-140512  " CSI ", " INFORM Labex   ANR-11-LABX-0054 ", " DCBIOL Labex   ANR-11-LABEX-0043 " with grants from  ANR-10-IDEX-0001-02 PSL* and A*MIDEX-ANR-11-IDEX-0001-02  funded by the " Investissements d'Avenir" French government program  managed by the  ANR.
The research was also supported by the  Ilídio Pinho Foundation and FCT  through the  Institute for Biomedicine-iBiMED  contract  UID/BIM/04501/2013  and  PTDC/IMI-IMU/3615/2014. We acknowledge financial support from n°ANR-10-INBS-04-01  France Bio Imaging  and the  ImagImm CIML imaging core facility. We acknowledge Drs. Lawrence and Bebien (CIML), as well as  Drs. Cazaret  and  Grelier (Lyon)  for providing GFP-vesicular stomatitis virus.
Neutral lipids Diacylglycerol (DAG) [M+NH 4 ] + [M+NH 4 -R 1 COONH 4 ] + >[M+NH 4 - R 2 COONH 4 ] + [39] Triacylglycerol (TAG) [M+NH 4 ] + [M+NH 4 -R 1/3 COO -] + >[M+ NH 4 - R 2 COO -] + [40] https://doi. org/10. 1371/journal. pone. 0182423. t001 Nebulizer pressure: 25 psi, Capillary voltage: ± 5000 V, Nozzle voltage ± 1000. Nitrogen was used as collision gas. The quadrupoles Q1 and Q3 were operated at widest and unit resolution respectively. Specific MRM scans used to define molecular species are summarized in S1 Table. Mass spectra were processed by MassHunter Workstation software (Agilent). For the MS/MS-Internal Stds method, each class of lipids (in the pmol range) was quantified with the corresponding internal standard. For the MS/MS-QC method, a QC sample is used as an external standard, and run with the list of the samples to be analyzed.
We have no clear explanation for this, but it is possible that the presence of two saturated FA such as 18:0 impacts differently the formation of ions in the ESI source compared to a mixture of unsaturated FA. To circumvent this problem, we systematically run in tandem with the unknown sample a lipid extract (QC), previously quantified by TLC plus GC-FID methods and having a FA composition more or less similar to the one to be analyzed. Indeed, when quantification were made using QC as a quantitative reference, the lipid distribution data determined by ESI-MS/MS were similar to those obtained from the TLC plus GC-FID method. In each class, the amount of lipid determined with the QC method is the sum of the various molecular species present in this particular class. Because the nature of the FA may also impact the number of ions formed in the ESI source, we cannot ascertain the absolute quantification of each molecular species.
Materials and Methods Bioinformatic analysis. Sequences identification and alignments. The S. cerevisiae Fzo1 target sequence was obtained from the UniProtKB database (Universal Protein Resource Knowledgebase  45  ), entry: P38297. A putative template was identified using the BLASTP tool (Basic Local Alignment Search Tool for proteins  46  ) against the PDB (Protein Data Bank  47  , with default settings. Homologues for the template in the phylum Cyanobacteria were then selected using the BLAST method (with default settings), from which a set of 43 sequences annotated as dynamin-like proteins was selected. The identity ranged from 22% to 87%, and the sequence coverage was greater than 65%. This set was then aligned with Expresso 48 using structural information from the template structure with PDB-id 2J68  16.
The T-Coffee method was used to align protein sequences from all the mitofusins belonging to the FZO1 family listed in Supplementary Table  1  that were used in this study. Structure prediction and model assessment. The secondary structure of Fzo1 was predicted from its sequence using the following algorithms: CONCORD  52  ; PSIPRED (v 3. 3) 53 ; PSSpred  54  ; and PORTER  55. The LigPlot+ program  56  was used to inspect the homologous residues in the target and template that contact the GDP substrate using a donor-acceptor distance of 3. 5 Å. The PCOILS v1. 0. 1 algorithm 57 was used to predict heptad periodicity in Fzo1 and BDLP. Disordered residues in the target sequence were investigated using the predictor DISOPRED3  25. Transmembrane domain. The BDLP template used for modelling Fzo1 possesses a hydrophobic region (res 572-606, Supplementary Fig.
Finally, guided by the secondary structure predictors, small adjustments were made to restore helices that were disrupted by insertions and deletions (indels). We combined three different templates to model the Fzo1 structure. The TM segments (res 706-726 and 737-757) were based on the ab initio model, the pentapeptide 216-220, which was unresolved in structure 2J68, was modelled on residues 98-102 from structure 2J69 (3. 0 Å  16  ), and the remainder of the protein followed structure 2J68. One hundred models were generated using the MODELLER program (v 9. 15)  61. The GDP nucleotide coordinates from structure 2J68 were included during the modelling procedure. During modelling, harmonic restraints were imposed on donor-acceptor distances, based on the LigPlot+ analysis of protein-nucleotide interactions in template 2J68.
These coordinates were subsequently manually adjusted by a 6° rotation around the x axis and a translation of -1. 5 Å along the z axis to improve the lipid-packing around the Fzo1 TM domain, and empty spaces in the bilayer were avoided during model building using the CHARMM-GUI pipeline (see below). Simulation setup and equilibration. The GROMACS 5. 0. 4 program was used to perform the MD simulations  69. The simulation system was assembled using the CHARMM-GUI Membrane Builder  70  with the CHARMM36 force field  71. In order to mimic the mitochondrial outer membrane composition, the protein model was embedded in a 1:1 mixed lipid bilayer composed of 156 molecules of palmitoyl-oleoyl-phosphatidylcholine (POPC) and 156 molecules of palmitoyl-oleoyl-phosphatidylethanolamine (POPE). The solvent is composed of a 150 mM KCl solution with 36,919 TIP3P water molecules  72.
Atomic positions were saved every 50 ps, and the first 100 ns were not used for the analysis. Trajectory analysis and molecular graphics. Root mean-square deviation (RMSD) and fluctuation (RMSF) analyses were performed using tools from the GROMACS package (g_rmsf and g_rmsf, respectively). A refined RMSD value was computed by omitting residues that fulfilled one or more of the following criteria: when a residue possesses a large RMSF value, is less conserved, unstructured, predicted to be disordered, hypothesized to be implicated in putative conformational change (e. g. , hinge regions), unresolved in the template, and involved in a progressive loss of folding. Secondary structure elements were identified using the do_dssp tool implemented in GROMACS based on the DSSP method  78. Hydrogen bonds and salt bridges were identified using g_hbond from GROMACS and VMD 1.
9. 2  79  (http://www. ks. uiuc. edu/Research/vmd/), respectively. Contacts within a distance cut-off of 3. 5 Å (and up to 30 degree off-axis angle) and 6. 5 Å were considered for H-bonds and salt bridges, respectively, to assess these interactions. Other analyses were conducted using in-house programs. When not otherwise specified, the persistence means how much the considered event occurs during the simulation time, expressed as a percentage over the number of frames. The cluster analysis was performed using g_cluster from GROMACS with the GROMOS method  80  , with a cut-off of 0. 25 Å. Molecular graphics were generated with the VMD 1. 9. 2  79  (http://www. ks. uiuc. edu/Research/vmd/) and UCSF Chimera 1. 9  24  packages. Data were plotted using Grace (http://plasma-gate. weizmann. ac. il/Grace/).
Primary antibodies were detected using horseradish peroxidase-conjugated secondary anti-mouse or anti-rabbit antibodies (HRP, Sigma-Aldrich, Saint-Louis, Missouri, USA), followed by incubation with a Clarity TM Western Kit (Bio-Rad, Hercules, California, USA). Images of the immunoblots were acquired using a Gel Doc TM XR+ (Bio-Rad) and analysed using the Image Lab 3. 0. 1 software (Bio-Rad). The anti-Fzo1 is not sensitive enough to detect ubiquitylated species of the mitofusin. For this reason, the ubiquitylation status of Fzo1 was analyzed using FZO1-13MYC strains and immunoblotting with anti-myc.
Acknowledgements Funding for this work was provided by the  French Agency for Research and "Initiative d'Excellence"  ( ANR-11-LABX-0011 , cluster of excellence LABEX Dynamo). This work was performed using HPC resources from  GENCI-CINES  (grant number  2016-072292 ). Research in the Cohen group was supported by the  CNRS-INSERM ATIP-Avenir program , the " fondation pour la recherche médicale" (INE 20100518343 ) and a  Marie Curie   IRG grant  (No. 276912 ).
Without the benet of a publication at the end of the tunnel, few scientists will engage in the hard work of trying to conrm or disprove the outcomes of others. They also assert that datasets are a valuable intellectual contribution in their own right that should be citable. Their list of simple reasons that work may fail to be reproducible, while drawn from another domain, should also sound familiar to those working in pattern recognition: dierent animal strains, dierent lab environments or subtle changes in protocol  [6]. All of these forms of bad behavior have analogs in our eld as well. We may think of using different test collections, dierent implementations of a standard machine learning technique, or dierent approaches to computing and reporting performance measures. The DAE platform, to be discussed in this paper, is our attempt to address some of these issues  [10, 13].
Robustness and Human Levels of Performance In developing algorithms that are robust and approach human levels of performance, we want algorithms to be general. This goal expresses the need for perception algorithms to perform well on tasks containing operational conditions or expected results that are dicult to formally dene  [9]  and for which one expects the resulting algorithm to perform equally well on new, previously unseen data. Measuring this robustness, or reproduce published results in controlled conditions is a challenging task, and often relies on benchmarking using reference data sets. One can observe, however, that too often methods are either tested on small, overused datasets, or especially in the context of recent deep learning developments in extremely large datasets that make it dicult to assess the breadth of scope they capture.
Improve upon Known Techniques The previous section relates to the aim of inventing new methods that are better than known techniques, and especially to the question of knowing whether we have succeeded  [17]. We already mentioned the fact that the need to compare against previously published results creates overreliance on standard datasets (which is counter-productive). Notwithstanding, comparing new approaches with previously published ones, under the same conditions and with the same data, is still important for the assessment of progress and ongoing improvement. However, attempts to re-implement a published algorithm are often problematic due to incomplete descriptions or even the inherent conict of interest that arises when attempting to show that one's own methods improve upon existing techniques  [19].
General Features From a general point of view, the DAE platform hosts a variety of data sets and algorithm implementations for document image analysis. However, the core feature of the platform is that all data is referenced in a central database on a ne-grained level. The full data model is described here  [13]. We are not going to further detail the data structure, here. This allows the platform to oer the following services: 1. It stores large data collections containing both raw document images, as well as an unlimited range of annotations. These annotations vary from high level content interpretations (like, for instance, text transcriptions, author identication or document structure) or pixel level segmentation information (binarization, shape outlines,. ). 2. All data can be hierarchically structured, and allows for convenient browsing through the collections.
Contributions to Software as a Service in a Controlled Environment: since availability of experimental data is only one of the requirements for open reproducible research, algorithms and software need to be made available as well. We have made the choice that, where software is concerned, reproducibility through availability of source code is not necessarily the best guarantee for replication of results. Initiatives like IPOL  [2] , github and others make it possible to thoroughly describe source code such that previously published methods can be reused and reimplemented. DAE pursues another goal: benchmarking and comparison. It therefore oers the possibility to run published reference applications in a controlled environment, as close as possible to the one used at the time of publication.
The SAAS/WSDL approach oers the possibility to linearly scale the platform and to distribute it over multiple locations. Individual contributors may choose to host their own software, rather than upload it to the centralized DAE platform. The downside, on the other hand, is that the hosting facility supports the costs for all executions, rather than having them supported by the experimenter; popular applications may become a burden for the hosting facility, since execution resources are expended on the server side. Experimental Protocols Made Explicit: as a by-product of the two previous features (data as a query/url and software as a service) it becomes easy to make experimental protocols explicit, sharable and reusable. We have explored  [11]  the use of web service orchestrating scripts like Taverna  [20]  and myexperiment.
Evolution from a WSDL interface to a REST interface Support for standard formats There are a large number of initiatives for the annotation and structuring of data extracted from digital documents, each adapted (or adopted) according to the eld of application. TEI Transition to a distributed data model and infrastructure The platform currently relies on a back oce consisting of an Oracle database and a centralized ZFS le system. In order to allow more exible interactions with instances hosted at dierent sites, and thus allow easy extension and sharing of ressources it would be appropriate to move to a more scalable structure of the NoSQL type. Virtualization One of the obstacles to the adoption of the platform is the need to use web services and encapsulate them in virtualized and safe environments.
Moreover, Fig. 4 (b) shows that the final error T is reduced for increasing initial correlations. While we have also studied entangled initial states, the data is not presented here, as the results do not differ. We find that only the amount of mutual information, i. e. , the total amount of correlations, not the type, i. e. , classical or quantum correlations, is relevant for cooling. A natural question is whether the speed limit reported in Fig. 4  depends on the type of control over the qubit. It turns out that a control field that couples to the system via σx Q instead of σz Q in Eq. (  1 ) does not perform better (data not shown). We have found solutions swapping the populations between qubit and memory TLS also for that type of control when starting from factorizing initial states. Similarly to σz Q -control, correlations in the initial state allow for better reset with smaller errors.
ACKNOWLEDGMENTS We thank  Jukka Pekola ,  Mikko Möttönen ,  Ronnie Kosloff ,  Pietro Liuzzo-Scorpo ,  Stefan Filipp ,  Felix Motzoi , and  Kondra Tulja Varun  for helpful discussions. Financial support from the  Volkswagenstiftung , the  Center of Quantum Engineering at Aalto University , the  Academy of Finland  (project no. 287750 ),  DAAD/Academy of Finland  mobility grants,  Agence nationale de la recherche  (grant no. ANR-15-CE30-0023-01 ), and the  PICS program  of the  CNRS  is gratefully acknowledged. This work was done in part with the support of the  Technische Universität München-Institute for Advanced Study , funded by the  German Excellence Initiative  and the  European Union Seventh Framework Programme  under grant agreement  291763.
Experimental Setup Given that solving a single optimization problem would not be enough to evaluate the approach, a sliding window is used. This way, instead of using all the data at once to estimate a single vector of future returns and a variance-covariance matrix, we define several subsets of returns for consecutive dates. This creates a number of partially overlapping single-period optimization problems that include a wide range of market conditions that are tackled one by one. More specifically, we start by defining a 10-year window consisting of the n = 120 consecutive months between January 2000, t 1 , and December 2009, t n. This data is subsequently used to estimate the parameters required to find the efficient frontier for January 2010, t n+1. Once this first problem is solved, we generate a second one that considers t 2 to t n+1 to estimate the vector of returns and the variance-covariance matrix for February 2010, t n+1.
• Stability This metric measures the sensitivity of the portfolios included in the efficient frontier to a number of potential scenarios where asset returns and their variance-covariance matrix deviate from the expected values. The stability of a portfolio is measured by averaging the Mahalanobis distances between the expected pair of risk-return in the efficient frontier and the expected risk-return in S different scenarios. The metric is calculated as follows: ST = 1 S S ∑ i=1 1 N N ∑ p=1 d M ( xp , xpi ) 2 , (13) where d M ( xp , xpi ) is the Mahalanobis distance between (E(R np ), σ 2 np ) and (E(R npi ), σ 2 npi ), the risk and return for portfolio p in the period t n computed using the parameters for the scenario i. A set of 500 likely alternative scenarios is generated from historical data by using a nonparametric bootstrap.
Acknowledgments:  Sandra Garcia-Rodriguez  and  David Quintana  acknowledge financial support granted by the  Spanish Ministry of Economy and Competitivity  under grant  ENE2014-56126-C2-2-R. Roman Denysiuk  and  Antonio Gaspar-Cunha  were supported by the  Portuguese Foundation for Science and Technology  under grant  PEst-C/CTM/LA0025/2013  (Projecto Estratégico-LA 25-2013-2014-Strategic Project-LA  25-2013-2014 ).
Such a beleaguered staff will need all the help that they can get; but, help needs to involve the implementation of tested and trusted techniques that provide product that is useful and that can be merged seamlessly into their response, forecasting and reporting duties (RED SEED Working Group 2016). That is, in the terminology of the remote sensing community, tools need to have been validated against reference data or 'ground-truth'  (Lillesand and Kiefer 1987) , so that they have gone from experimental to operational  (Rudd 1974) , thereby being known, trusted, valid and useable. Such help needs to be tested before, not during, a crisis (RED SEED Working Group 2016). In this case, the best way-forward is an ensemble approach whereby external (to the observatory) partners with pertinent expertise are invited to contribute to the response effort.