dataesr/scientific-paragraphs-categorization huggingface dataset:
Judges had expertise in epidemiology, demography, sociology, anthropology, clinical medicine, health behaviour and management. Each submission was reviewed by at least four judges and numerically scored on a 1-10 scale, 10 being the best. Scores for each contribution were averaged, and those with an SD greater than 2. 5 were reviewed by two additional judges. After collating judge scores, 47 entries achieved a mean score of 7 or greater, emerging as semifinalists. These were further reviewed by the steering committee, which ultimately selected 18 finalists based on the mean score achieved coupled with the desire to balance participant demographics and experience working in HIC and LMIC settings. Among finalists, 83% (15/18) had LMIC sexual health research experience. This group included principal investigators on LMIC sexual and reproductive health studies, data analysis experts, sociologists, demographers, epidemiologists, reproductive health leaders and others with experience in developing national surveys and analysing multicountry data.
For the consensus statement, participants graded each of the statements. Items that achieved 100% agreement were graded as 'U' (unanimous); 90%-99% agreement were 'A'; and 80%-89% agreement were 'B', and items with less than 80% agreement were not included. The steering committee reviewed all grading and made final decisions. Sixty people were invited to take part in the first-round online survey focused on consensus statements and 47 (78%) responded. This survey included 12 statements on principles of sexual health survey design (7), training (2) and implementation (3). Participants who responded indicated expertise in survey design, piloting, data management, data analysis and field work. Two statements on the design stage did not reach 80% agreement and were revised for the second round.
g. , some sex workers); participants from low-income countries and participants from upper middle-income countries; participants who have limited English language proficiency (B1 intermediate level). Administration. We will focus on a survey administered with forms on mobile phones, tablets, or computers that do not have regular internet. Data can be collected offline and later uploaded. It will be interviewer administered with self-administration for selected components. BMJ Publishing Group Limited (BMJ) disclaims all liability and responsibility arising from any reliance Supplemental material placed on this supplemental material which has been supplied by the author(s).
Small working groups have also worked to revise Phase 1, Phase II and efficacy trial behavioral risk assessments. Revisions are informed by analysis of behavioral data collected in HVTN phase 1, 2, 2b, and 2b/3 clinical trials as well as data obtained in the extant literature. Development and inclusion of assessment questions focuses on identifying variables that are most predictive of HIV risk and ensuring that assessments provide data that will be utilized and do not place unnecessary burden on the participants and site staff in the trials. Dr. Andrasik has also participated in team efforts to analyze BRA data for inclusion in primary and secondary protocol manuscripts. More recently, she has engaged in an intensive systematic review to identify variables predictive of HIV seroconversion among sub-Saharan African heterosexual women.
Martina Morris is an emeritus professor of Sociology and Statistics at the University of Washington. She has worked on the development of study designs and statistical methodology for social network data for over three decades, with specific applications to the projection and optimal control of HIV and other STIs. Her experience includes studies conducted in HIC and LMIC settings, with qualitative and quantitative components, and administration ranging from interviewer-based paper or mobile platforms to online data capture, with projects ranging from basic research to implementation science. She heads a large interdisciplinary team of researchers committed to the development of accessible reproducible research tools. They collectively develop and maintain a suite of open-source software packages written in the R programming language for statistical network analysis (statnet) and the mathematical modeling of infections across networks (EpiModel), teach annual courses on the use of these tools, and are collaborating to develop a new interactive graphical user interface for network data collection online (Network Canvas).
Martina Morris Martina Morris is an emeritus professor of Sociology and Statistics at the University of Washington. She has worked on the development of study designs and statistical methodology for social network data for over three decades, with specific applications to the projection and optimal control of HIV and other STIs. Her experience includes studies conducted in HIC and LMIC settings, with qualitative and quantitative components, and administration ranging from interviewer-based paper or mobile platforms to online data capture, with projects ranging from basic research to implementation science. She heads a large interdisciplinary team of researchers committed to the development of accessible reproducible research tools. They collectively develop and maintain a suite of open-source software packages written in the R programming language for statistical network analysis (statnet) and the mathematical modeling of infections across networks (EpiModel), teach annual courses on the use of these tools, and are collaborating to develop a new interactive graphical user interface for network data collection online (Network Canvas).
Groups and clusters from IllustrisTNG The hydrodynamical cosmological simulation IllustrisTNG  (Nelson et al. 2019)  follows the evolution of dark matter, gas, stars, and black holes on a moving mesh (code Arepo, Springel 2010) from redshift z = 127 to z = 0. The input cosmology of the simulation is consistent with Planck 2015 results  (Planck Collaboration et al. 2016) , such that Ω Λ,0 = 0. 6911, Ω m,0 = 0. 3089, Ω b,0 = 0. 0486, σ 8 = 0. 8159, n s = 0. 9667, and h = 0. 6774. We focus on the largest simulation box IllustrisTNG300-1 with a size length of 302. 6 Mpc and with the highest mass resolution of m DM = 4. 0 × 10 7 M /h (2500 3 DM particles). We chose to use this high-resolution and large simulation box to accurately describe the shape and dynamical state of the massive halos. For each snapshot, the IllustrisTNG simulation provides a halo catalog, identified with a standard friends-of-friends (FoF) algorithm with linking length b = 0.
Acknowledgements. The authors acknowledge the useful comments of the anonymous referee. This research has been supported by the funding for the  ByoPiC  project from the  European Research Council (ERC)  under the European Union's  Horizon 2020 research and innovation program  grant agreement  ERC-2015-AdG 695561  (ByoPiC, https://byopic. eu). The authors thank the very useful comments and discussions with all the members of the  ByoPiC team. The authors acknowledge the use of the IllustrisTNG publicly available data.
Data were recorded at 100 K (Fyn R96I ) or 295 K (Fyn R96W ) at λ = 1. 54 Å, using the Rigaku 200 X-ray generator, confocal multilayer mirrors (Osmic), and a MAR300 image plate detector. Data were integrated, merged, and scaled using Mosflm  [39]  and Scala  [40]  (Supplementary Table  S1 ). All data were checked using ContaMiner  [41] , and the initial phases were determined by molecular replacement using Molrep  [42]. For Fyn R96I (crystal form I) and Fyn R96W SH3, Fyn R96 SH3 was used as a template (Protein Data Bank PDB ID 1SHF)  [43]. Fyn R96I (form I) was used as a template for Fyn R96I (crystal form II). The structures were refined using Refmac  [44]  and COOT  [45]  (Supplementary Table  S1 ; PDB IDs, 3HOF, 3HOH, and 3HOI). In a second round of crystallization experiments, Fyn R96I with a C-terminal hexahistidine tag (see  [46]  for cloning details) was crystallized in 0.
1 M citric acid at a pH of 3. 5 and 25% w/v polyethylene glycol 3,350. The crystals were cryoprotected with 25% glycerol and diffracted to 1. 34 Å resolution at the SOLEIL synchrotron beamline PROXIMA 2A, France. The hexahistidine tag stabilized the crystal packing (Supplementary Figure  S1A , Supplementary Table  S1 ; PDB ID 6IPY). Fyn R96W SH3 was crystallized in 0. 08 M sodium acetate trihydrate at a pH of 4. 6, 1. 6 M ammonium sulfate, 20% v/v glycerol, and 50 mM 18-crown-6. Crystals diffracted to a 1. 57 Å resolution at PROXIMA 2A. The CCP4 online version of MoRDa was used to determine the structures  [47] , followed by rebuilding through BUCCANEER  [48] , and manual and automated refinement (REFMAC5, PHENIX)  [49, 50]. Two 18-crown-6 molecules were identified (Supplementary Figure  S1B , Supplementary Table  S1 ; PDB ID 6IPZ).
Crystals of the HIV-1 Nef 58-205 -Fyn R96W SH3 complex were obtained via the hanging-drop vapour diffusion method at 18°C-20°C. Before crystallization, stoichiometric amounts of Nef 58-205 and Fyn R96W SH3 were mixed, concentrated to obtain 0. 35 mM of Nef-SH3 complex, and filtered. Then, 1 ml samples of this solution were mixed with 1 ml of the reservoir buffer containing 0. 25-0. 3 M sodium potassium tartrate, 0. 5 M bicine buffer ( pH, 8. 4), and one critical micelle concentration β-D-octylglucopyranoside. Crystals were cryoprotected by rapid transfer into 28% glycerol, 0. 3 M sodium potassium tartrate, and 0. 5 M bicine buffer ( pH, 8. 4). The crystals were then flash-cooled in liquid nitrogen, and data were collected at 100 K at the FIP beamline at the European Synchrotron Radiation Facility (Grenoble, France) using the MAR345 image plate detector.
The images were processed and scaled using Mosflm  [39]  and Scala  [40]. Crystal phases were obtained by molecular replacement using LΔN-Fyn R96 and WLΔN-Fyn R96I SH3 complex structures as templates (PDB IDs 1AVZ and 1EFN). The structure was refined using Refmac  [49]  and Phenix  [50]  (Supplementary Table  S2 ; PDB ID 4D8D). SF2 Nef-Fyn R96I SH3 complex crystals were obtained by the sitting-drop vapour diffusion method at 18°C-20°C. Before crystallization, stoichiometric amounts of full-length SF2 Nef and Fyn R96I SH3 were mixed, concentrated to obtain 1 mM of Nef-SH3 complex, and filtered. Then, 1 ml of this solution was mixed with 1 ml of the reservoir buffer containing 0. 10 M calcium acetate hydrate, 0. 10 M sodium acetate buffer ( pH, 4. 5), and 10% w/v PEG 4000. The crystals were cryoprotected by a rapid transfer into 28% glycerol, 0.
10 M calcium acetate hydrate, 0. 10 M sodium acetate buffer ( pH, 4. 5), and 10% w/v PEG 4000. All data for SF2 Nef-Fyn R96I SH3 were collected at 100 K at PROXIMA 2A with an EIGER 9 M detector ( proposal numbers 2016 0098, 20161236, and 20170193). Data from three crystals were processed, scaled, and combined using XDS as implemented in the XDSme pipeline (unmerged data are available at https://doi. org/10. 25781/KAUST-8CV15). STARANISO  [51]  was used for merging the three datasets and for establishing the anisotropic resolution limits. Initial phases were determined using MoRDa  [47]  with the PDB ID 4D8D as the molecular replacement template (Q score, 0. 834). The structure was manually corrected using COOT and refined using LORESTR  [52]  (Ramachandran outliers/favourite 2. 53/91. 14%) (Supplementary Table  S2 ; PDB ID 7D7S).
Molecular dynamics simulations Molecular dynamics simulations were carried out in triplicates for apo-Nef (Nef-A) and Nef in a complex with Fyn R96I (Nef-C), using the 2. 5 Å resolution crystal structure of LAI Nef T71R bound to Fyn R96I (PDB ID 1EFN) as a template. MD simulations were performed using GROMACS 2018  [53]  with the AMBER14SB force field  [54]. Each protein was inserted into a cubic box filled with TIP3P water molecules. Box size was chosen to have a minimum distance of 10. 0 Å from the protein edges to the box sides. The system was neutralized with Na + and Cl -ions. Energy minimization was performed followed by equilibration using isothermal ensemble dynamics (NVT) with a velocity-rescale thermostat  [55]  for computing velocities and atom positions. The structures were further equilibrated for 2 ns with isothermal-isobaric ensemble dynamics (NPT).
Microscale thermophoresis Proteins were labelled using the Monolith protein labelling kit RED-NHS 2nd Generation. The concentrations of the labelled protein ranged from 10 to 50 nM. The concentrations of unlabelled preincubated SH3 and H1 were 50 mM and 1 mM, respectively. Measurements were performed at 25%-50% LED and 40% microscale thermophoresis powers. Data were analyzed using the program provided by Nanotemper Technologies. All MST experiments were performed in 50 mM Tris ( pH, 8. 0), 200 mM NaCl, 2 mM EDTA (excluded in HIS tag purification), and 1-2 mM DTT at 20°C.
Presence of SH3 domains influences binding of the N-terminal Nef helix Our ITC data suggested that the presence of the flexible N-terminal Nef residues influenced the association of Nef with SH3 domains. This Nef region contains an amphipathic helix (termed H1, comprising residues 15-22 in LAI; Figure  1A ) that helps to anchor Nef to the charged lipid headgroups of the cellular membrane  [23]. In structural studies of full-length Nef, this H1 helix has been observed to bind to the hydrophobic groove formed by the core helices ɑ1 and ɑ2 and the connecting residues (see PDB IDs 6CRI, 4EN2, and 6CM9). In this report, we refer to this region as the ɑ1-ɑ2 groove. This groove is adjacent to, but not overlapping with, the SH3-binding site  [35, 36]. We synthesized a Nef fragment containing H1 (residues 8-26) to test its affinity for the different Nef constructs in the presence or absence of the SH3 Fyn R96I and Fyn R96W variants.
SH3 binding decreases the dynamics of specific Nef regions Our assays showed that the binding of the SH3 domain increased the affinity of Nef for H1 and vice versa, which suggests the existence of allosteric cooperativity. To further investigate this phenomenon, we performed MD simulations comparing the Nef core domain in its apo state (denoted Nef-A) with its Fyn R96I -complexed state (Nef-C). We derived Nef-A and Nef-C from the 2. 5 Å resolution crystal structure of LAI Nef 54-205,T71R bound to Fyn R96I (PDB ID 1EFN  [20] ). This crystallographic Nef model lacked residues 54-70 and 149-177, making it akin to the molecule we defined as ΔNΔL. In MD simulations, Nef-C had lower calculated van der Waals and electrostatic energy, and showed decreased overall mobility compared with Nef-A [root mean square fluctuations (RMSF) were 2.
52 ± 1. 88 Å for Nef-A and 2. 16 ± 1. 32 Å for Nef-C] (Figure  3A-D ), Supplementary Data SDS1. S1), indicating that the SH3 domain stabilized and rigidified Nef. The RMSF differences were greatest in the residues of the N-terminal arm and the core domain loop (Figure  3B ). Within the core domain, residues 75-80 showed the strongest stabilization in Nef-C, as expected from their direct interaction with the SH3 domain (Figure  3B, E ). However, this SH3-induced stabilization also extended to the underlying residues 111-126, including the C-terminal part of the ɑ2 helix. Additionally, Nef residues 101 to 102 and residue 138 showed fewer fluctuations in the SH3 domain complex (Figure  3B, E ). Thus, a large part of the H1 binding site was stabilized by the SH3 domain as was a region that interacts with CD4  [37]  and contributes to Nef-Nef crystal contacts (observed in PDB IDs 1EFN, 1AVV, 1AVZ, 4USW, 3REA, and 3D8D) and possibly to dimerization in vitro  [69]  (Figure  3F, G ).
W 57 L was also associated with the ɑ1-ɑ2 groove, albeit in a different position, in a crystal structure of SF2 Nef bound to an engineered high-affinity SH3 domain (3REA  [70] ). However, other crystallographic studies of the core domains of HIV-1 and SIV Nef show the ɑ1-ɑ2 groove occupied by the endocytosis motif from the core domain loop of an adjacent molecule in the crystal lattice (PDB IDs: SIV, 5NUH and 5NUI; HIV, 3RBB). The binding positions of the endocytosis motifs in HIV and SIV Nef in these crystals were again different  [71, 72]. Investigating the LAI Nef 54-205,T71R -Fyn R96I structure (PDB ID 1EFN), we found strong, continuous residual density in the ɑ1-ɑ2 groove in both Fyn R96I -bound Nef molecules of the asymmetric unit (Supplementary Figure  S1 ). In both molecules of the asymmetric unit, the electron density region closest to W 57 in the NMR model provided a good fit for a tryptophan side chain whereas the adjacent density fits a leucine side chain.
However, both can be outcompeted by H1. Further evidence for the capacity of H1 to outcompete other intramolecular regions comes from our survey of the available experimental structures (PDB IDs 6CRI, 4EN2, and 6CM9) (Supplementary Table  S3 ). This survey showed that whenever the H1 motif is present in Nef, it occupies the ɑ1-ɑ2 groove rather than W 57 or the core loop. In the 3. 5 Å crystal structure of full-length LAI bound to Fyn R96I that we determined in this study (PDB ID 7D7S; Supplementary Table  S2 ), the ɑ1-ɑ2 groove was partly occluded by adjacent molecules in the crystal lattice, further supporting the hypothesis that also the H1-core association has a low affinity and can be easily displaced.
Fyn r96w mutation alters the SH3 RT loop hydrogen-bond network In our ITC titrations, we observed that increasing the hydrophobicity of the SH3 R position from isoleucine to tryptophan resulted in a less favourable entropy contribution, which suggests that the incorporation of tryptophan caused additional loss of degrees of freedom upon binding (Table  1 ). To compare the RT loop features of apo-and Nef-bound Fyn and Hck SH3 domains, we produced the missing crystal structures of the ligand-free Fyn R96I and Fyn R96W (PDB IDs 3HOF, 3HOH, 3HOI, 6IPY, and 6IPZ; Supplementary Table  S1 ). We observed that the apo Fyn R96 and Fyn R96I structures had a similar strong RT loop-rigidifying network formed by six hydrogen bonds (Figure  4 ). Conversely, the NH group of Fyn R96W disrupted the RT loop hydrogen-bond network and produced an RT loop that was more flexible in its free state.
In cases where the R position is an isoleucine (Hck and Fyn R96I ), W113 is rotated towards the SH3 domain and away from the hydrophobic crevice compared with apo-Nef (Figure  5B ). Conversely, W113 is pushed into the hydrophobic groove in Fyn R96W -bound Nef structures, whereas W113 adopts an apo side-chain orientation when Nef is in a complex with Fyn R96. Thus, binding to SH3 domains with isoleucine in the R position increases the adjacent ɑ1-ɑ2 groove by 2. 3 Å, whereas tryptophan decreases the groove by 0. 9 Å; and an arginine leaves it relatively unchanged. Next, we superimposed the available experimental structures of HIV-1 Nef bound to its N-terminal H1 (EM: PDB IDs 6CM9, 6CRI; X-ray diffraction: 4EN2) with the Nef-SH3 complexes. In the Nef-H1 structures, the malleable N terminal of H1 partly occupies the same Nef region as the R position in the Nef-SH3 complexes.
SH3 for Fyn R96W but not for Fyn R96I , shows a Hck SH3-like reduced RT-loop hydrogen-bond network (PDB IDs: Hck, 1BU1; Fyn R96 , 1SHF; Fyn R96I , 3H0I; Fyn R96W , 6IPZ). characterized by the duplication of the RAEP motif situated at the C-terminus of H1, and even though this motif has not been predicted to contribute to the intramolecular association, it may have subtle effects on the interaction. Assessing the prevalence of Nef-like SH3 selectivity based on Fyn R96 In the context of previous work, our analysis of the 'tertiary' association between an SH3 domain and Nef demonstrated that the combination of a linear interaction motif and a folded core domain can create opportunities for synergy and allostery in addition to enhancing affinity and selectivity. Given the promiscuity of SH3-PR motif interactions  [74, 75] , these 'tertiary' features might also be useful for increasing the selectivity in cellular SH3-based signalling.
Acknowledgements We acknowledge SOLEIL for the provision of synchrotron radiation facilities. We also thank  L. Chavas ,  P. Legrand ,  S. Sirigu , and  P. Montaville  for their assistance with beamline PROXIMA 1 and  G. Fox ,  M. Savko , and  B. Shepard  with  PROXIMA 2A. We also thank  M-P. Struband  and  M-T. Augé-Sénégas  for the initial cloning of some of the Fyn  R96I  and Fyn R96W mutants. We thank  M. Geyer  for providing the expression construct of Nef  SF2. We acknowledge the staff at  ESRF beamline BM30, Grenoble, France , for their assistance with crystallographic data collection. We also thank the  KAUST Supercomputing Laboratory  for their assistance with computational resources for molecular dynamics simulations using the IBEX cluster.
Data Availability All crystallographic data are deposited in the Protein Data Bank (Fyn SH3 domain mutants, 3H0F, 3H0H, 3H0I, 6IPY, and 6IPZ; Nef-Fyn complexes, 4D8D and 7D7S). Additionally, unmerged crystallographic data are available as PDB ID 7D7S at https://doi. org/10. 25781/KAUST-8CV15.
As part of an assessment framework for AD, this paper presents a DCP compliant implementation of an interoperable interface between a 3D environment and vehicle simulator and a cosimulation platform. A universal Python wrapper is implemented and connected to the simulator to allow its control as a DCP slave. A C-code-based interface enables the co-simulation platform to act as a DCP master and to realize cross-platform data exchange and time synchronization of the environment simulation with other integrated models. A model-in-the-loop use case is performed with the traffic simulator CARLA running on a Linux machine connected to the co-simulation master xMOD on a Windows computer via DCP. Several virtual vehicles are successfully controlled by cooperative adaptive cruise controllers executed outside of CARLA.
This synchronization scheme is the most widespread one in the ADS and automotive domain including commercial simulators, standards, and stateof-the-art research. (2) RQ2 (support for software and model formats) A co-simulation master is required that supports the integration and performant execution of multiple models on its platform with native support for software and model formats widespread in the ADS domain. At least the master shall support the integration of C/C + + code, MATLAB/Simulink models, and functional mock-up units (FMUs). (3) RQ3 (standardized communication layer for tool coupling) In order to support the incorporation of models, software, or hardware that are incompatible with the co-simulation master tool or platform and therefore cannot be integrated using established methods, a standardized, non-functional interoperability interface shall be implemented that allows for the integration of autonomous tools and platforms as co-simulation slaves.
In any case, after each state change, the master needs to be notified about the new status. States are provided inter alia for the parametrization of the slave and handling of runtime synchronization and data exchange, which meets RQ7 and RQ8. Interoperability is achieved without the standardization of any functionality realized by the slave. Instead, functional aspects such as the inputs, outputs, and parameters are documented in the DCP slave description file which provides all static configuration data of the slave to the master  [16]. Only the schema of such a DCP slave description file is explicitly defined as part of the DCP standard while it has to be filled by the implementer of the slave. As a result, DCP supports the exchange of master or slave in line with RQ5. It does also guarantee the support of various transport layer protocols covering TCP and UDP (RQ9).