dataesr/scientific-paragraphs-categorization huggingface dataset:
The Canadian Institutes of Health Research is providing funds to support ADNI clinical sites in Canada. Private sector contributions are facilitated by the Foundation for the National Institutes of Health (www. fnih. org). The grantee organization is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer's Disease Cooperative Study at the University of California, San Diego. ADNI data are disseminated by the Laboratory for Neuro Imaging at the University of California, Los Angeles. We would also like to thank the Swedish Foundation for Strategic Research (SSF), the Strategic Research Programme in Neuroscience at Karolinska Institutet (StratNeuro), Hjärnfonden, and Birgitta och Sten Westerberg for additional financial support. J. B. P. was funded by a Marie Curie fellowship for postdoctoral researchers (grant No.
Detection of CTC The patient was recruited into a clinical research program (VADS -EudraCT N°: 2010-A00586-33, approved by the regional ethic committee "Comité de Protection des Personnes Est III"), which aimed to evaluate the prognostic value of CTC in HNSCC. Venous blood samples were collected at three time points (preoperative day-1, intraoperative, and postoperative day 7) for the detection of CTC. The manipulations were performed by using the Cell-Search ® system (Veridex LLC, Raritan, NJ) according to a standard protocol  [13]. The commercially available Cell-Search ® Tumor Phenotyping Reagent Epidermal Growth Factor Receptor (EGFR) kit (Veridex LLC, Raritan, NJ, USA) was used on the fourth channel of fluorescence of the CellSearch ® system following the manufacturer's instructions. The pre-, intra-, and post-operative enumerations of CTC are shown in Fig.
Mitochondria from WFS1-deficient neurons also changed their direction during motion more often and made more individual runs, whereas the length of these runs was shorter. These data explain the oscillatory-like movement we frequently observed in WFS1-deficient neurons (S2 and S3 Videos). We also measured the contact rate of mitochondria as an indirect parameter of mitochondrial movement. This parameter was also significantly reduced in neurons isolated from Wfs1-deficient mice and restored by WFS1 overexpression (S6 Fig).
The density of axonal mitochondria is reduced in Wfs1silenced neurons (J) and in neurons isolated from Wfs1 -/-mice (K). This parameter is restored by wt WFS1 overexpression, but Wfs1 shRNA has no effect. *p < 0. 05, **p < 0. 01, and ***p < 0. 001 compared with respective control groups. Underlying data is shown in S1 Data. doi:10. 1371/journal. pbio. 1002511. g001 mitochondria. We also performed indirect reactive oxygen species (ROS) measurements using an NRF2 reporter gene assay, which showed no difference between the scrambled and Wfs1 shRNA-transfected neurons (Fig  2B ). Next, we estimated cell ATP levels using the fluorescence resonance energy transfer (FRET)-based ATP sensor ATeam, which employs the epsilon subunit of a bacterial F 0 F 1 -ATPase. Control experiments with deoxyglucose/oligomycin or glutamate reduced neuronal ATP levels and demonstrated the expected decline in FRET signal, showing the validity of our approach (Fig  2C ).
Mitochondrial Density and Length For whole-cell mitochondrial density measurements, the neurons were transfected with GFP, mitochondrial pDsRed2, scrambled shRNA or shRNA, and plasmids of interest. At DIV 8, the entire axon and dendrites from randomly selected neurons were visualised using a laser scanning confocal microscope. Neurons were reconstructed using Neurolucida and LSM5 software, and mitochondrial density was analysed. Mitochondrial length measurements were performed as described previously  [39].
Neuronal Maturation, Axonal Growth, and Synaptic Density For neuronal maturation experiments, cortical neurons were transfected at DIV1 with a plasmid expressing neuron-specific pAAV-hSyn-DsRed1 and scrambled shRNA or Wfs1 shRNA. Live-cell morphology was visually examined using a fluorescence microscope (Olympus IX70, 20x/0. 70 water immersion objective) on randomly selected fields (minimum 30 fields per group) on the indicated days in culture. Neurons were classified into the four subgroups depending on their maturation stage (Type I: lamellipodia; Type II: immature neuron, sprouting of several minor neurites; Type III: axon and dendrite formation, neuronal polarisation and branching; Type IV: neuron with adult-like morphology, ongoing maturation of differentiated processes). For the axonal growth analysis, images of cultured cortical neurons (DIV2 to DIV6) were captured using an Olympus IX70 inverted microscope with a 20x objective and traced manually using Neurolucida software (MBF Bioscience).
RT-PCR Total RNA was isolated from age-matched Wfs1 -/-and Wfs1 +/+ using the Qiagen RNeasy Mini Kit. Conversion to cDNA was performed by reverse transcription using 1 μg of total RNA with SuperScript III RT kit (Invitrogen). Specific primers were designed for amplification of Mfn2, Mfn1, Opa1, Drp1, Fis1, Miro2, and Cox4 genes. qPCR was performed on an ABI PRISM 7900HT Sequence Detection System. Reactions were performed using an ABI SYBRGreen PCR Master Mix, and raw data were analysed using the ΔΔCt method. All Ct values were normalised to the control gene synaptophysin (SYN).
Acknowledgments We thank  Dr. T. Iwawaki ,  Dr. R. Youle ,  Dr. R. Rizzuto ,  Dr. Szabadkai ,  Dr. Alam , and  Dr. E. Deas  for providing the plasmids used in this study. We thank  Ulla Peterson  for her preparation of primary neurons. We also thank  Indrek Heinla ,  Mait Nigul ,  Katarína Jašková ,  Lucia Lichvarova ,  Liia Feoktistova ,  Ksenja Labonarskaja , and  Victoria Vdovenkova  for their help.
Immunofluorescence Fixed prostate sections were deparaffinized in xylene and antigen retrieval was performed by in 10 mM sodium citrate, 0. 05% Tween 20 (pH 6. 0) for 20 minutes in a microwave oven. Sections were blocked in 10% normal goat serum with 1% BSA in PBS for 2 hours and incubated with primary antibodies overnight at 4°C. Primary antibodies used were SOX4 (# 86809; 1:200; Abcam, Cambridge, MA) and Cytokeratin 8 (TROMA-I; 1:6; Developmental Studies Hybridoma Bank, Iowa City, IA). Secondary antibodies were Alexa Fluor® 546conjugated goat anti-rabbit (A11010; 1:1,000: Molecular Probes, Eugene, OR) and Alexa Fluor® 488-conjugated goat anti-rat (A11006; 1:1,000: Molecular Probes, Eugene, OR), incubated for 1 hour at room temperature in the dark. Sections were counterstained with Hoechst dye, mounted with Fluoromount-G (SouthernBiotech, Birmingham, AL), visualized using Nikon Eclipse 80i (Tokyo, Japan), and images were captured at 200× total magnification using SPOT Advanced software (Sterling Heights, MI).
PARIS Analysis of Achilles and CCLE Datasets The version 2. 4. 3 release of Project Achilles data (http://www. broadinstitute. org/achilles) with ATARiS gene level scores for 216 cell lines passing quality control (p=0. 05) were analyzed using the PARIS (Probability Analysis by Ranked Information Score) module on the Broad Institute GenePattern server. Cancer Cell Line Encyclopedia (CCLE) mRNA expression data (http://www. broadinstitute. org/ccle/home) from Affymetrix U133+2 arrays was downloaded and integrated with Achilles Data in the PARIS analysis. Analysis was performed with default parameters examining negative RNMI values to identify shRNA's from Achilles that are selected against in cells with high SOX4 expression levels.
Analysis of Prostate Adenocarcinoma TCGA datasets Normalized RNAseqV2 data was downloaded from the Broad Institute genome data analysis center (http://gdac. broadinstitute. org/runs/analyses__latest/). Copy number and mutational data for PTEN, PIK3CA, and PIK3CB were obtained from the cBioPortal website using the TCGA PRAD provisional dataset for 419 cases with expression, copy number, and mutational data available (http://www. cbioportal. org/index. do). Patients with homozygous loss of PTEN, hemizygous loss of PTEN plus a mutation of the retained allele, or mutations in either PIK3CA or PIK3CB were designated as having the pathway mutated. Other patients were considered as not mutated. SOX4 level 3 gene expression RNAseq data was used to determine if SOX4 levels was significantly different between groups.
Cancer Cells with High SOX4 are Sensitive to AKT1 shRNA Knockdown To test whether the relationship between SOX4 and AKT is generalizable to other types of cancer, we mined the publicly available datasets from Project Achilles  (27)  and the Cancer Cell Line Encyclopedia (CCLE)  (28). We applied the PARIS (Probability Analysis by Ranked Information Score) module from GenePattern  (29) , which uses the rescaled normalized mutual information (RNMI) metric to identify statistically significant gene interactions in large datasets. The Achilles 2. 4. 3 dataset includes shRNA sensitivity data on 5711 genes in 216 cancer cell lines derived from approximately 20 tissue types, including three prostate cancer cell lines (22RV1, NCIHCC60, and VCAP), while the CCLE dataset includes gene expression data from 1037 cell lines, including 215 of the Achilles cell lines.
PARIS analysis of the overlapping data from the Achilles and CCLE datasets to identify shRNA targets that are associated with high expression of SOX4 identified six genes with a false discovery rate (FDR) < 0. 05. Interestingly, cell lines with high SOX4 gene expression were highly sensitive to shRNAs that target the AKT1 gene (p = 1. 75e-5, FDR = 0) (Figure  4G ), suggesting that combined targeting of SOX4 and AKT1 could have synergistic effects.
Our analysis of Achilles and CCLE datasets across 215 cell lines from 20 tissue types supports the hypothesis that SOX4 interactions with AKT1 are important in many types of cancer, and also suggests that drug combinations that target both SOX4 and PI3K-AKT might have synergistic effects. Another important question relates to the role of the PTEN-PI3K-AKT pathway, SOX4, and tumor metastasis. Recently, several studies have identified PTEN as not only a critical tumor suppressor gene, but also as a metastasis-suppressor gene  (33, 34). In each of these studies PTEN deletion seemed to cooperate with KRAS activation, RB1 loss, or CDKN2A deletion to promote tumor metastasis. SOX4 has also been shown to play an important role in metastasis, since shRNA knockdown of SOX4 inhibited lung metastases of breast cancer xenografts  (6)  and SOX4 acts as a master-regulator of EMT in breast cancer cells  (22).
Inhibition of AR signaling has no effect on SOX4 expression. (F) LNCaP cells were treated with human EGF for 24 hours, followed by the treatment of 1 µM or 10 µM of MEK1/2 inhibitor Selumetinib. Inhibition of MAPK/ERK pathway has no effect on SOX4 expression. (G) PARIS analysis of Achilles and CCLE datasets shows that cancer cells with high SOX4 are sensitive to AKT1 shRNA knockdown.
Acknowledgments Financial support: This research was supported by  NIH  grant  R01CA106826  and  NIH U01 CA168449. This research was supported in part by the  Amy & Nevin Kreisler Research Award , a philanthropic award provided by the  Winship Cancer Institute of Emory University. Research reported in this publication was supported in part by the  Cancer Animal Models Systems Shared Resource of Winship Cancer Institute of Emory University  and  NIH/NCI  under award number  P30CA138292. DM was supported by the  Centre National pour la Recherche Scientifique (CNRS) , the  Institut National de la Santé et de la Recherche Médicale (INSERM) , the  Fondation ARC pour la Recherche sur le Cancer  and the  Ligue Nationale Contre le Cancer , and by  French  state funds through the  Agence Nationale de la Recherche   ANR-10-LABX-0030-INRT  under the frame programme  Investissements d'Avenir labelled   ANR-10-IDEX-0002-02.
As stated previously, a single detection of limb activity is required to describe the full-body state. Accelerations and angular velocities were collected from the four limbs and pelvis using IMUs located on the right and left wrists, right and left feet, and pelvis. The IMUs combined a triaxial accelerometer (±8G), a triaxial gyroscope (1600 • /s) and a triaxial magnetometer (MotionPod, Movea c , Grenoble, France) referenced to magnetic North, sampled at 100Hz. Wireless transmissions to a controller enabled recording with MotionDevTool software (Movea c , Grenoble, France). A wearable device is required to measure climbing activities on a 10m-high climbing wall.
Recording and preprocessing The acceleration of each sensor was determined from the recorded signals. These data were used to synchronise the video recording of the climb with the IMU signals in the learning phase of the detection, as well as to detect activity. Therefore, this method had to be used even on unlabelled sets of climbing. Although the sensors directly record the acceleration in the sensor frame, the recording cannot be used directly as proper acceleration because of the gravity component. The norm of this component is wellknown (9. 81m/s 2 ), but it cannot be removed from the sensor frame without knowing the orientation of the sensor in the ground reference frame. Let a s be the recorded acceleration in the sensor frame. By denoting R the rotation matrix describing the sensor frame in the Earth reference frame (magnetic North, West and vertical up direction), the ac-Figure  1 : Example of the frame difference between the ground frame (red), where the gravity is known, i.
This paper focuses on the application of a Petri Net-based diagnosis method on a planetary rover prototype. The diagnosis is performed by using a model-based method in the context of health management of hybrid systems. In system health management, the diagnosis task aims at determining the current health state of a system and the fault occurrences that lead to this state. The Hybrid Particle Petri Nets (HPPN) formalism is used to model hybrid systems behavior and degradation, and to define the generation of diagnosers to monitor the health states of such systems under uncertainty. At any time, the HPPN-based diagnoser provides the current diagnosis represented by a distribution of beliefs over the health states. The health monitoring methodology is demonstrated on the K11 rover. A hybrid model of the K11 is proposed and experimental results show that the approach is robust to real system data and constraints.
A hybrid model of the rover is proposed, based on the discretization of its health evolution. Experimental results are given, illustrating how the methodology is robust to real system data and constraints. The method exposed in  [11]  have been improved. It is hence recalled and new notions are precised, such as the definition of events, the mode scores or the scale parameters for example. This paper is organized as follows. Section 2 presents related works on diagnosis of hybrid systems. Section 3 recalls and deepens the health monitoring methodology based on the modeling of the system and the generation of a diagnoser by using HPPN. Section 4 focuses on the application of the proposed methodology on the K11 planetary rover prototype. It provides the K11 hybrid model and exposes the experimental results and performance metrics.
Rover Description The K11 rover is powered by twenty-four 2. 2 Ah lithium-ion single cell batteries. A typical mission of the rover consists in visiting and performing desired science functions at a set of waypoints, before joining its charging station. A decision making module (DM) is responsible for determining the order in which to visit the waypoints according to the terrain map, the waypoint positions and rewards, and the rover conditions. The rover has four wheels, denominated by their location: the front-left (FL) wheel, the front-right (FR) wheel, the back-left (BL) wheel and the back-right (BR) wheel. Each wheel is driven by an independent 250 W graphite-brush motor, with control performed by a single-axis digital motion controller. An onboard laptop computer runs the control and data acquisition software.
Results The HPPN framework is implemented in Python 3. 4. The tests were performed on a 4 Intel(R) Core(TM) i5-4590 CPU at 3. 30 GHz with 16 GB of RAM and running GNU/Linux (Linux 3. 13. 0-74, x86 64). In order to reduce computation time, the token value update step is multithreaded on the 4 physical cores. The rest of this implementation only uses one core. Two scenarios studied in  [23]  are considered in this work. The rover mission is to visit a maximum of 12 waypoints and to go back to its starting position. All waypoints have different associated rewards. In nominal conditions, the rover DM system returns a 5-waypoints path, starting and finishing at the same position. For all scenarios, the K11 rover starts at 0s with batteries fully charged and with all components at the ambient temperature.
The model and diagnoser have been generated and two scenarios have been tested to illustrate the proposed method advantages. The diagnoser results are consistent with the expected ones and show that HPPN-based diagnosis is robust to real system data and constraints and adaptable to systems without discrete observations nor degradation knowledge. In future work, futher scenarios will be tested. We also aim at formalizing and developing a prognosis process that will interleave diagnosis and prognosis methods to obtain more accurate results. The HPPN-based prognostics methodology will be defined and tested on a three-tank system as well as on the K11 rover.
The PCR was performed in a DNA Engine Thermal Cycler (PTC-200, BIO-RAD, USA) with a hot starting performed at 94°C for 3min, followed by 30 cycles of 94°C for 0. 5min, 55°C for 0. 5min and72°C for 1min, followed by a final extension performed at 72°C for 10min. The PCR products were commercially sequenced by Sigma Company using ABI 3730xl DNA sequencer with the two primers. The 16SrRNA sequence was compared against the GenBank database using the NCBI BLAST program. Sequences were then compared with 16SrRNA sequences in the GenBank database using BLASTN. Multiple sequence alignment was done using ClustalX 1. 8 software package and a phylogenetic tree was constructed by the neighbour joining method using MEGA (Version 6. 1) software. The confidence level of each branch (1,000 repeats) was tested by bootstrap analysis.
Analytical methods The culture growth was estimated based on OD 600 measurements using a visible spectrophotometer. After OD 600 measurements, the cultures were centrifuged at 6,000rpm for 10min and the supernatants were subjected for glucose and LA determination. Residual glucose in the broth was estimated by using 3, 5-dinitrosalicylic acid reagent (DNS method). 17 LA was measured by Barker and Summerson method. 19 Firstly, LA was converted to acetaldehyde through oxidation with concentrated sulphuric acid. Acetaldehyde after that was coupled with p-hydroxy diphenyl in the presence of cupric ions forming a purple compound. The absorbance of this purple compound was measured by using spectrophotometer at 570nm. All experiments were conducted at triplicates, data were statistically analyzed by SPSS v17, analysis of variance (ANOVA) test was used for multiple sample comparison, when normality and homogeneity of variance were satisfied, followed by multiple comparison Tukey test.
Strain BoMAir 5 cannot tolerate higher concentration of NaCl than 7. 5%. The acid production was compared to those of other Psychrobacter references strains such as Psychrobacter arenosus KMM 3659  T20  and Psychrobacter piscatorii T-3-2 T. 21 Surprisingly, BoMAir 5 can tolerate higher temperature until 55°C with optimum temperature at 40°C that differ from other reported Psychrobacter strains that cannot grow above 37°C. In addition, Strain BoMAir 5 cannot haemolyse human blood agar plates indicating the bio-safety of this strain. Molecular identification based on 16srRNA gene sequence analysis of BoMAir 5 strain showed the identity of 99% to Psychrobacter maritimus strain pi2-20 (accession number NR 027225). The phylogenetic tree showed that the topology of BoMAir 5 strain to Gamma proteo-bacteria (Figure  1 ).
Acknowledgments This work would not have been possible without the useful advice of  Iosif Bena ,  Pablo Bueno ,  Tomás Ortín ,  Carlos S. Shahbazi ,  David Turton  and  Nick Warner. The project has been supported in part by the  Spanish Ministry of Science and Education  grant  FPA2012-35043-C02-01 , the  Centro de Excelencia Severo Ochoa Program  grant  SEV-2012-0249 , the  Severo Ochoa pre-doctoral grant   SVP-2013-067903 , the  EEBB-I-16-11563  grant and the  ERC  Starting Grant 259133 ObservableString. Last but not least, I am thankful to  Nieves López  for drawing Figure 1 and for asking me to marry her.
A very important aspect of building trust is for the objectives review to maintain links to source documents and also to keep track of versions when the RG and Header Group input is obtained. If there is a need to speed up the process, a generic objective tree to develop management strategies for coastal zone fisheries and biodiversity can be used and the lower level (the objectives) can be subsequently added for more local content (Fig. 4 ). Determining the objective relative weighting can be kept within the Header Group and RG (rather than going to the community as well), as this data will be used when the management strategies are created by the Header Group and RG. Obtaining objectives weightings from the community is time consuming. However, if a community survey is part of the project plan can be obtained, doing local radio interviews in which the link to online surveys is  publicised seems to work well in obtaining participation  (Dichmont et al.
The project team should collate these using a database and provide these to the RG for input. The Header Group should support the final product. Given the time usually available, particularly to senior managers, the impact assessment should be undertaken for the highest level objectives by both the RG and the Header Group prior to the key managers meeting. It can be repeated in session at the managers meeting to obtain information on influence e see example tables in  Dichmont et al. (2014). Undertaking the impact assessment at these two separate meetings highlights relative priorities and the difference between managers and RG members. The analysis method is provided in  Dichmont et al. (2013 Dichmont et al. ( , 2014)). At least one managers meeting between senior managers, embedded managers, the Header Group and RG should be undertaken.
Acknowledgements This work would not have been possible without the incredible input from the  Mackay and Bowen-Burdekin community , and their associated LMAC members. Most notably, those that helped us tirelessly in Mackay as members of the Mackay LMAC RG. We developed a survey in Mackay to gauge residents' opinions of what mattered to them with regard to coastal management, and more than 140 completed what was a taxing survey. These respondents also helped recruit other survey participants. Some of the participants attended in-person sessions held in Mackay and stayed to give us robust advice on the survey design. These comments were instrumental when developing a new method. Special mention must be made of Carolyn Thompson, GBRMPA, Mackay e her involvement and tireless work was probably the most significant factor allowing us to get real traction in Mackay.
Image acquisition Images taken using a confocal microscope (Zeiss LSM700) were processed with ZEN 2011 software (Carl Zeiss MicroImaging) and Photoshop CS6. All confocal views are single planes (thickness 0. 8 mm) except panels in Fig. 4  A2-A4 and B2-B4, which are maximal projections of 3 mm. Dorsal whole-mount views of the midbrain were taken using a Nikon macrozoom.
Acknowledgements We thank members of our team, as well as  Aurélie Heuzé  and  Jean-Stéphane Joly , for helpful comments and discussions. This work was supported by the  French Agence Nationale de la Recherche  (grants  ANR-08-CEX-08-000-01  and  ANR-2012-BSV4-0004-01 ), the  Ecole des Neurosciences de Paris  (Chair of Excellence 2010), the  FRM  ( FRP " Equipe " DEQ20120323692 ) and the  European Research Council  ( AdG 322936 ).