dataesr/scientific-paragraphs-categorization huggingface dataset:
The OSPO is therefore building on what has happened in the private sector, but it is expanding and extending this in the context of the university. I am also pleased to note that while Johns Hopkins created the first OSPO in a university in the United States, there are now at least three others at the University of California, Santa Cruz, at the Rochester Institute of Technology and at the University of Vermont. It is my understanding that there will be additional universities creating these OSPOs, so we can see ourselves coming together as a network of these organisations. Johns Hopkins is involved in a project called the Observational Health Data Sciences and Informatics, or OHDSI project 2. Paul Nagy is a researcher in our School of Medicine who is involved in this project. He approached me after hearing about our OSPO saying that they needed help.
To go a step further "There is a very important growing movement around ethics in data. The same is true of software. We sometimes talk about biases that are embedded within data, within the tools or algorithms used to process those data through software. There is absolutely an ethical component to working on software, even if it is open source, but one of the good things about open source software is it is transparent, so we have a better chance of seeing what is actually being done in terms of analysing the data. " Research Data the Open Science Award for Thesis. The call for entries for the Open Science Research Data Award is underway, and we will grant this award by summer 2022. The first edition of the Open Science Award for Thesis will take place in 2023. We can use this conference days to honour the winners of this first edition of the Open Science Research Awards.
| METHODS We provide the phenotypic and genetic data of a young boy carrying biallelic TSPYL1 variants. Written informed consent was obtained from the parents and the study was approved by the Local Ethics Committee. The clinical data have been registered in the PhenomeCentral database (ID P0010838, see URLs section). We also reviewed the data of the 21 previously described cases and the 5 recently reported patients with SIDDT. Panel gene test libraries were built using a custom design based on a SeqCap EZ Solution-Based Enrichment strategy (Roche Nimble-Gen) and paired-end sequencing 2 Â 150 bp was performed on a Nextseq 500 (Illumina). Targeted regions included coding exons ±50 bp together with 5 0 and 3 0 -UTR for 22 candidate genes identified in DSD (list of genes available on request).
Genomic alignment against the hg19/GRCh37 assembly and variant calling used respectively. Only high confidence variants were kept for analysis (total depth >9; alternative allele depth >4; no strand bias; mosaicism >10%). Rare variants were considered as having a frequency <1% in gnomAD v2. 1 control database. Variations were classified according to the American College of Medical Genetics (ACMG) guidelines  (Richards et al. , 2015). Sanger sequencing confirmation was systematically performed for SNV and short indels classified as likely pathogenic or pathogenic. In order to exclude a double diagnosis that could explain the neurological phenotype, we also performed exome sequencing (ES) using a previously described method  (Nambot et al. , 2018).
3). These variants were previously reported six and two times, respectively, in the gnomAD population database in heterozygous carriers. Global allelic frequencies were 0. 002% and 0. 0007%, respectively. Both variants were classified as likely pathogenic, following the 2015 ACMG guidelines (Richards et al. , 2015), because the frameshifts were assumed to disrupt TSPYL1 function (PVS1) and according to the absence of homozygous carrier and very low heterozygous frequency in general population (PM2). ES did not return any additional candidate variants that could explain the epileptic phenotype. At the age of 4. 5 months, he presented repeated episodes of abnormal hyperextension movements with eye revulsions and desaturation. Monotherapy with levetiracetam was introduced, but within a month the patient's neurological condition deteriorated considerably.
ACKNOWLEDGMENTS We thank the family for agreeing to participate in this research. We thank the  Centre de Calcul (CCuB) of the University of Burgundy  for technical support and management of the informatics platform, and the Genematcher platform for datasharing. This work was supported by grants from the  Dijon University Hospital ,  ISITE-BFC (PIA ANR ), and the  European Union  through the  FEDER  programs. The authors wish to thank  Suzanne Rankin  ( Dijon Bourgogne University Hospital ) for reviewing the English manuscript.
ACKNOWLEDGMENTS This research has been supported by the  Spanish Ministry of Science, Innovation and Universities (MICINN)  through grants  IJC2018-037897-I, FPU19/00601  and  PID2019-111436RB-C22 , by the  Agència Valenciana de la Innovació  through grants  INNCON/2021/8  and  INNVA1/2020/92 , by  Generalitat Valenciana  through grant  AICO/2020/268. Action co-financed by the  European Union  through the  Programa Operativo del Fondo Europeo de Desarrollo Regional (FEDER)  of the Comunitat Valenciana  2014-2020  ( ID-IFEDER/2018/022 ) and ( IDIFEDER/2021/004 ). Action cofinanced by  BPI France ,  Région Grand Est  and  FEDER  ( UFOGUIDE  project).
DESTINY-Breast01 (NCT03248492) evaluated trastuzumab deruxtecan (T-DXd; DS-8201) in patients with heavily pretreated HER2-positive metastatic breast cancer (mBC). We present a subgroup of 24 patients with a history of treated brain metastases (BM), a population with limited treatment options. In patients with BMs, the confirmed objective response rate (cORR) was 58. 3% [95% confidence interval (CI), 36. 6%-77. 9%], and the median progression-free survival (mPFS) was 18. 1 months (95% CI, 6. 7-18. 1 months). In patients without BMs (n = 160), cORR was 61. 3% and mPFS was 16. 4 months. Eight patients (47. 1%) experienced a best overall intracranial response of partial response or complete response. Seven patients (41. 2%) had a best percentage change in brain lesion diameter from baseline consistent with stable disease.
The tumor microenvironment may cause enhanced vascular permeability, allowing for the extravasation of large mole cules, such as antibody-drug conjugates (ADC), through the BBB. In a preclinical study of the HER2-targeting ADC trastuzumab emtansine (T-DM1), it was proposed that the enhanced vascular permeability of the BBB may lead to adequate concentrations of T-DM1 in BMs to elicit a clinical benefit  (9). Trastuzumab deruxtecan (T-DXd) is an ADC that comprises a humanized, monoclonal, anti-HER2 antibody with a topoisomerase I inhibitor payload attached via a plasma-stable, tumor-selective, cleavable, tetrapeptidebased linker  (10, 11). Based on the DESTINY-Breast01 (NCT03248492) and DESTINY-Breast03 (NCT03529110) studies  (12, 13) , T-DXd was approved for the treatment of patients with unresectable or metastatic HER2-positive breast cancer after a previous (United States) or ≥2 previous (various countries worldwide) anti-HER2-based regimens  (14, 15).
Based on HER2CLIMB, tucatinib in combination with trastuzumab and capecitabine was recently approved for patients with HER2-positive mBC, Abbreviations: BOR, best overall response; N/A, not applicable (no brain lesion present at baseline); NR, nothing reported; RT, radiotherapy (brain-specific). a Includes BM-specific treatment for past BMs and any at baseline. These data were collected retrospectively. b Imaging was performed per protocol every 6 weeks for subjects with baseline BMs. Measurements were not required per protocol but were performed by some sites and collected retrospectively. For subjects without measurements, imaging was performed, but measurements were either not taken or not provided by the study site. including those with BMs, after ≥1 prior (United States) or ≥2 prior (Europe) lines of HER2-targeted therapy  (18, 19).
Additionally, a clinical benefit rate of 75% (12/16) was observed in a retrospective cohort of breast cancer patients with BMs (21). In the phase II TUX-EDO-1 trial (NCT04752059), T-DXd demonstrated efficacy and safety in patients with HER2-positive breast cancer with newly diagnosed BMs or BMs with radiologic progression after prior local therapy. Intracranial response was observed in 11/15 patients (73. 3%; ref. 22 ). In the phase III DESTINY-Breast03 trial, 23/36 (63. 9%) patients with stable BMs at baseline experienced intracranial CR or PR  (23). In the ongoing phase II DEBBRAH trial (NCT04420598), T-DXd demonstrated preliminary efficacy in patients with HER2-positive advanced breast cancer with stable, asymptomatic untreated, or progressing BMs after radiotherapy and/or surgery. Intracranial ORR was reported in two patients (50.
0%; 95% CI, 6. 7-93. 2) with asymptomatic untreated BMs and four patients (44. 4%; 95% CI, 13. 7-78. 8) with treated and progressing BMs  (24). The ongoing DESTINY-Breast07 (NCT04538742), DESTINY-Breast09 (NCT04784715), DESTINY-Breast12 (NCT04739761), and HER2CLIMB-04 (NCT04539938) trials will continue to assess the efficacy of T-DXd in patients with HER2-expressing breast cancer and BMs, including active BMs. Patients with HER2-negative mBC comprise approximately 85% of the mBC population, and approximately 60% of tumors from patients with HER2-negative mBC express low levels of HER2  (25, 26). T-DXd was approved in the United States for the treatment of patients with unresectable or metastatic HER2-low (IHC 1 + or IHC 2 + /in situ hybridization -) breast cancer after prior chemotherapy in the metastatic setting based on results from DESTINY-Breast04 (NCT03734029; ref.
27). Therefore, the data reported here suggest that a large subset of patients with mBC and BMs may experience clinical benefit with T-DXd. The ongoing DESTINY-Breast06 (NCT04494425) and DESTINY-Breast08 (NCT04556773) studies, and a cohort from DEBBRAH, are continuing to assess HER2-low patients with treated/stable BMs. DESTINY-Breast01 did not include patients with active BMs, and 19 of 24 patients in the BM subgroup had received prior surgery or radiation to the brain. BMs were to be listed as nontarget lesions; although BMs were monitored by imag-ing every 6 weeks (Q6W), diameter measurements were not required. In addition, our subgroup analysis included only 24 patients, of whom 17 had brain lesion measurements available for analysis. Tumor measurements were obtained retrospectively by contacting the treating investigators, and the date of data cutoff could not be independently verified.
Endpoints The data cutoff for this analysis was August 1, 2019. The primary endpoint was cORR (CR + PR) per ICR using Response Evaluation Criteria in Solid Tumors, version 1. 1. Secondary endpoints were investigator assessed and included duration of response, PFS, OS, DCR (CR + PR + SD), safety, and best percentage change in the sum of the longest diameters of measurable tumors. The primary and secondary endpoints were determined for all patients who received the recommended dose of T-DXd 5. 4 mg/kg (previously described; ref. 12)  and are presented here for patients with and without a history of BMs.
Acknowledgments This project has received funding from the  European Union   Horizon 2020 research and innovation program AQUACOSM-plus  under grant agreement No  871081. MG, DCM, JCN, SAB, MB, KAG, SL were supported by  INFRAIA   EU-H2020  AQUACOSM-plus and MB by  EU-H2020 ,  PONDERFUL (No 869296 ) project. MS and PT were supported by the  German Research Foundation   DFG STR 1383/8-1. MCP was supported by the  Irish Marine Institute  funded under the  Marine Research Program  by the Irish G o v e r n m e n t n a m e d B E Y O N D 2 0 2 0 ( G r a n t -A i d Ag r e e m e n t No. PBA/FS/16/02 ) and the  AQUACOSM TA grant  ( 2019 ) under the project name AlloEcoMetry. FP was supported by  H2020-MSCA-ITN ECORISK2050  project (Grant Agreement nr. 813124 ). SBF was supported by  NSF   DEB 1856415.
RMC was supported by  MARHOT  project from the  EU H2020  research and innovation programme under the  Marie Skłodowska-Curie  Grant  N 894941. JV and CP were supported by the G e r m a n R e s e a r c h F o u n d a t i o n D F G ( G r a n t N u m b e r :  P A 2643/2/348431475 ). Open Access funding enabled and organized by Projekt DEAL. WOA Institution:  CARL VON OSSIETZKY UNIVERSITAET OLDENBURG Consortia Name  : Projekt DEAL Submitted 18 February 2022 Revised 14 September 2022 Accepted 28 September 2022.
A vertex that belongs to  is referred to as a dominating vertex or a dominator, and a vertex that is not a member of  is referred to as a dominated or a dominatee or a non-dominating vertex. The minimum directed dominating set problem (MDDS) consists in finding a directed dominating set on  having minimum number of vertices. The minimum weight directed dominating set problem (MWDDS) is a generalization of MDDS and seeks a directed dominating set on  with minimum sum of weights of its constituent vertices. As directed graphs regulation  (Wuchty, 2014; Wang et al. , 2014). Concept of domination in digraphs has also been used for routing in ad hoc wireless networks with unidirectional links  (Wu, 2002)  and processing skyline queries in databases  (Koltun and Papadimitriou, 2005). MDDS is used in case of homogeneous networks.
Graph reduction pre-process The following properties can be used as a pre-processing step to remove edges from the digraph , and discard some vertices from the search of an optimal solution to MWDDS. use any multi-core features. Our approaches are executed once on each instance of the dataset. All the datasets have ten instances in a group for each combination of the same number of nodes (| |) and the same number of directed edges (||) or the same range (). We have reported for each approach the average solution quality and the average execution time on each group of ten instances like the usual practice of reporting results in case of MWDS. Parameter values for our ABC and IWO approaches are chosen empirically after a large number of trials. First, we will describe the ABC parameter values.
H1, H2, H3, H4 and H5  (Nakkala and Singh, 2020). These five heuristic approaches are the only approaches available in the literature for MWDDS. These tables report the average solution quality on each group of 10 instances obtained by various approaches under the columns named after respective approaches. These tables also report the average execution times in seconds on each group of 10 instances for ABC, IWO, ILP and MH under the columns named after respective approaches with subscript  , i. e. , columns entitled ABC  , IWO  , ILP  , MH. Execution times of H1, H2, H3, H4 and H5 being negligible will not be reported. Table  2  present the detailed results on UDG instances, Table  3  on Type-I instances and Table  4  on Type-II instances. Table  5  present the summary of comparisons among our 4 proposed approaches in terms of number of groups of instances in each dataset and overall on which an approach mentioned in the left performs better than (B) or same as (E) or worse than the approach mentioned at the top.
From these tables, following observations can be made: • As expected, all the four proposed approaches performed better than the five heuristics available in the literature on all the groups of instances in all the three datasets. • IWO performed better than ABC in general, and the performance gap between them widens as the instance size increases. • Barring 10 groups of instances in Type I dataset, where ILP could not finish in allotted time of 3600 s on some instances, it performed as good as or better than IWO and ABC both. • MH performed as good as or better than IWO and ABC both except for 2 groups of instances in Type I dataset where ABC performed better. It is to be noted that MH will always perform as good as IWO due to its very design where IWO is one component. • All UDG and Type II instances were solved to optimality by ILP and MH both with maximum execution time of around 100 s.
Moreover, ILP and MH are several times faster than IWO and ABC on these two datasets. • MH performed as good as or better than ILP on all groups of instances except for one group of instances in Type I dataset. MH can perform worse than ILP only on those instances where ILP can find a better solution after  1 amount of time in comparison to the solution that it got within  1 amount time. • MH never required the maximum allotted time of 3600 s. It has terminated before that time in all the cases. • Among the 4 methods that we have proposed, MH has performed the best. This is not surprising as for different dominating set variants, matheuristic methods are currently the best performing methods, e. g. Albuquerque and Vidal (2018) ,  Pinacho-Davidson et al. (2019), and Nakkala et al. (2021). These matheuristic approaches not only provide solutions of better quality, but are also faster than several metaheuristic approaches for the same problem in most cases.
Conclusions Minimum weight dominating set problem (MWDS) and minimum directed dominating set problem (MDDS) are well-known variants of minimum dominating set problem and many approaches are available in the literature to solve them. However, the minimum weight directed dominating set problem (MWDDS) that has several real-world applications and can be considered as a generalization of MWDS and MDDS both has not received much attention. Only five problem specific heuristics were available in the literature  (Nakkala and Singh, 2020) , and this problem has neither been studied in the literature from metaheuristic perspective nor from integer linear programming perspective nor from matheuristic perspectives. This paper proposed two swarm intelligence based metaheuristics, viz. ABC and IWO, an ILP approach and a matheuristic approach MH and experimentally evaluated their performance on three datasets derived from respective datasets of MWDS.
RenderX The Database Our analysis was grounded on the material included in 2 recently published reviews dedicated to conventional CTIs  [11]  and exergames  [12] , respectively. Specifically, 24 studies on conventional training and 23 studies on exergames, published from 2010 to November 2021, were selected on the basis of several criteria  [11, 12]. These studies were then analyzed to compare them according to the 4 chosen constructs of our framework (Table  1  and Table 2 ).
, 2010) ). Determination of the reduced cysteines can then be investigated by chemical digestion, mutagenesis or by mass spectrometry (MS). Similarly, methionine oxidation of actin can be identified by MS (increase of 16 Da for sulfoxide methionines) (reviewed in  (Ghesquière and Gevaert, 2014) ). However, MALDI ionization creates a highly oxidative environment that can oxidize methionines during measurements, making it hard to quantitatively assay the amount of actin oxidized in samples  (Ghesquière and Gevaert, 2014). Only state-of-the-art approaches (e. g. using reagents with heavy oxygen (O 18 ) that react with reduced methionines before MS analysis) can quantitatively determine the amount of oxidized methionines in vivo. Recent data revealed that 13-20% of Met190 in actin is oxidized, but tryptic peptides with two methionines (such as M44, M47) were not analyzed  (Bettinger et al.
Acknowledgments The authors thank  Drs. Miria Ricchetti ,  Neetu Gupta-Rossi  ( Institut Pasteur ) and  Guillaume Romet-Lemonne  ( Institut Jacques Monod ) for critical reading of this manuscript. We thank  Olena Pylypenko  ( Institut Curie ) for her help in preparing Fig. 2B. Several illustrations were created with  BioRender. com. Oxidation work in the Echard lab  has been funded by the  Institut Pasteur , the  CNRS, ANR RedoxActin , the  Fondation pour le Recherche Médicale :  FRM EQU202103012627  (to AE),  ANRS-21020 AP2020-2  (to SF) and  SIDACTION 2021-1-FJC-13007  (to TS). We acknowledge  Ecole Doctorale Frontières de l'Innovation en Recherche et Education -Programme Bettencourt " to TS.
Synthesis of Cellulose Acetate-g-PCL Cellulose acetate (1 g) was dissolved in anhydrous THF (50 mL), and separately, PCL-NCO (7. 5 g) was dissolved in anhydrous THF (100 mL) and an appropriate amount of DBTDL. The cellulose acetate solution was slowly added to the PCL-NCO solution while stirring for 30 min. The mixture was then stirred at 80 • C for 3 h under N2 gas atmosphere. The reaction mixture was cooled to room temperature, and then excess methanol was added to the mixture. The precipitate was recovered by vacuum filtration and the unreacted PCL-NCO was removed by Soxhlet extraction with toluene for 24 h. To evaluate the grafting of PCL onto cellulose acetate, ATR-FTIR was used. The spectra were determined on a FT/IR-4700 spectrometer (JASCO, Japan). The data were collected in the spectral range of 400 to 4000 cm -1.
COMPUTER MODEL A computer program that uses mathematical calculations and rules to reproduce the functioning of an organ (like the liver, in our case) and predict how things will behave under di erent conditions. like a GPS or Google Maps: using calculations and some information about the tra c, it can help scientists figure out which roads are blocked, and which are not. In our case, computer models helped us to guess which metabolic roads were used by the metabolites, giving us new ideas about what may be happening in the liver. We could then check these ideas using other experiments. It searches paths that were followed by the metabolites present in the incoming vessel to obtain the metabolites present in outgoing vessels. For example, in the "healthy" condition, glucose but not pyruvate was present in the outgoing vessel, meaning that glucose was produced by the liver and pyruvate was used up.
In addition to a changing job market, other changes in research culture may also impact the training of ECRs. For example, there has been an increase in international, interdisciplinary and team-based science  (39) , with more authors per paper and greater amounts of data included in individual publications  (40, 41). To investigate the effect of these trends on life science training outcomes in Europe, we performed a time-resolved analysis of the career paths of 2284 ECRs who completed a PhD or postdoc at the European Molecular Biology Laboratory (EMBL) between 1997 and 2020. EMBL is an intergovernmental life science research organisation with six sites in Europe. The organisation's missions include scientific training, basic research in the life sciences, and developing and offering a wide range of scientific services; it currently employs more than 1110 scientists in research and service teams -including over 200 PhD students and 250 postdoctoral fellows focussed on research.
EMBL has a long history of training PhD students and postdocs, and was one of the first life science institutes in continental Europe with a structured PhD programme. Fellows in the EMBL International PhD programme have a completion rate of 92% and submit their PhD thesis after 3. 95 years on average (data for 2015-2019). More recently, EMBL has launched dedicated fellowship programmes with structured training curricula for postdocs. This study is, to our knowledge, the first analysis of training outcomes data published by a European research institute. Furthermore, our time-resolved data analysis enables a better understanding of how career outcomes have been changing with time, and how this may extrapolate to the future job market for current ECRs. Finally, our study also links career outcomes to other data, including publication record, to better understand training outcomes.