dataesr/scientific-paragraphs-categorization huggingface dataset:
When this kinome-wide dataset was used to predict specific kinases responsible for substrate phosphorylation solely based on the amino acid sequence surrounding the phosphorylation site, the results were remarkably accurate at identifying correct kinase-substrate relationships, even without knowledge of tissue specificity, scaffolding effects, or subcellular localization. Including such additional information is likely to further improve these predictive approaches  74, 75. Interrogation of MS phosphoproteomic datasets using this global collection of motifs yielded new potential biological insights and new putative kinase substrates (Fig. 4 ). For example, in cells undergoing exposure to ionizing radiation (Fig. 4e ), ATM was predicted to target 35 of the phosphorylation sites that were upregulated, most of which have never been associated as substrates for ATM (Table  S3 ).
Plasmids For expression and purification from bacteria, DNA sequences for the human Ser/Thr kinases, kinase binding partners, and chaperones listed below were codon-optimized for E. coli using GeneSmart prediction software (Genscript). Optimized coding sequences were synthesized as gBlocks (Integrated DNA Technologies) carrying 16-base pair overhangs at the 5' and 3' ends to facilitate in-fusion cloning (Clontech) into pET expression vectors (EMD MIllipore). pCDFDuet1 constructs: HSP90AA1-His6 (full length), hereafter referred to as "HSP90," untagged HSP90 (full length), His6-MO25a (full length), His6-ALPHAK3/ALPK1 NTD (1-474), and His8-CCNC (full length) in tandem with MED12-His8 (1-100), and untagged CK2B (full length). pACYDuet1 construct: Untagged CDC37 (full length).
with a centralized phosphor-acceptor (serine and threonine at a 1:1 ratio) and one fixed amino acid in a randomized background. All 20 natural amino acids, plus two PTM residues (phospho-Thr and phospho-Tyr), were substituted into positions -5 to +4 to generate 198 unique peptide mixtures (22 amino acids X 9 fixed positions). After reaction, peptides were separated were spotted on streptavidin-conjugated membranes (Promega #V2861) where they tightly associated via their Cterminal biotinylations. The membranes were rinsed to remove free ATP and kinase and imaged with Typhoon FLA 7000 phosphorimager (GE). Raw data (GEL file) was quantified by ImageQuant (GE). For the kinase ALPHAK3, spots were normalized to surrounding background, due to spatial variation in background signal. PDHK1 and PDHK4 showed dual specificity for serine and tyrosine.
Matrix clustering The dendrogram in Fig. 2  was generated using the normalized matrices with the 20 unmodified amino acids, as well as phosphothreonine and phosphotyrosine. Linkage matrix was computed through the SciPy package in Python (v1. 7. 1), using 'ward' method. Results were converted to Newick tree format and plotted using FigTree (v1. 4. 4).
Kinase enrichment analysis The single phosphorylation sites (not including multi-phosphorylated peptides) in the analyzed phosphoproteomics studies were scored by all the characterized kinases (303 S/T kinases), and their ranks in the known phosphoproteome score distribution were determined as described above. For every non-duplicate, singly phosphorylated site, kinases that ranked within the top-15 kinases for the S/T kinases were considered as biochemically favored kinases for that phosphorylation site. For assessing kinase motif enrichment in phosphoproteomics datasets, we compared the percentage of phosphorylation sites for which each kinase was predicted among the upregulated/downregulated (increased/decreased, respectively) phosphorylation sites (sites with |log2Fold-Change| equal or greater than the logFC threshold), versus the percentage of biochemically favored phosphorylation sites for that kinase within the set of unregulated (unchanged) sites in this study (sites with |log2Fold-Change| less than the logFC threshold).
Sequence logos Sequence logos were made using logomaker package in Python 30. For individual kinases, the normalized matrix was used, where the height of every letter is the ratio of its value to the median value of that position. The serine and threonine heights in the central position (position zero) were set to the ratio between their favorability, and to sum up to the maximal height in the peripheral positions. For clustered groups of kinases, the average matrix was calculated and presented as sequence logo as described above.
Comparative analyses between amino acids in the kinase domains and their substrate specificities For Fig. S7 , kinases were sorted by their log2(S0/T0) values. For the sequence logo, kinase domains of 290 available kinases were obtained from previously aligned kinase sequences [PMID: 31875044]. The alignments to residues Met1-Leu296 in CDK2 (PDB: 1QMZ) were obtained for each kinase, and the frequencies of amino acids for each 15 kinases were calculated and plotted as a sequence logo.
Subsequently, they mounted, on a goniometer head, a single-crystal of the MOF with incorporated BCDD and flushed with nitrogen at 50 °C for 5 h to remove the residuary solvent. Then, they collected XRD data at 100 K, and reported the structural model of BCDD@BUT-17 (refcode: JOMZOD in the Cambridge Structural Database). The authors positioned the BCDD molecules at the borders of the large hexagonal channels, bound to the framework through the cooperation of π-π stacking, hydrogen bonding and "molecular clipping" with the formate groups. After a first inspection of the structure, one is immediately impressed by the unusually large displacement parameters (U iso ) of the BCDD atoms, despite a partial occupation of only 16%, fixed without any justification. Moreover, the model does not consider the inherent disorder due to the molecule sitting about an mm2 symmetry site.
The accuracy of the model can be easily evaluated by the Fourier maps that we computed from the deposited diffraction data. We used the same software adopted by the authors (Shelxl 2 implemented in Olex2 3 ) and assigned the phases of the structure factors from the reported model. The map of the total electron density in the plane of BCDD (Fourier transform of F obs ) reveals no maximum corresponding to atoms of the molecule included in the model (Fig. 1a ). For comparison, Fig. 1b  shows the same map in the region of the organic linker, which instead clearly stands out. We then removed the BCDD from the reported BCDD@BUT-17 and refined a guest-free model. The agreement indices are nearly identical to those for the model including the guest molecule (R 1 = 5. 66% versus 5. 62%, respectively).
Computational details The three-dimensional EtP5A host-guest complexes including the hydrocarbon molecules, octane, 1,7-octadiene, and 1,7-octadiyne, were generated from the pdb format using Autodock-Vina software  [46] , which allows to predict the binding free energy of complexes. The EtP5A host was used as a rigid receptor, and Autodock Tools  [47]  was used to determine the possible rotations of bonds by molecular docking. During the simulation, the ligands (guest molecules) were docked to the EtP5A with box dimensions set to Accepted manuscript / Final version the grid (22 × 24 × 24) Å 3 in volume, and the cartesian coordinates center was set to 0. 017, -0. 021, and -0. 097 Å. The docking configuration with the highest free-energy score (∆G) was used as the starting geometry conformations for the DFT calculations.
The structures of all species, including the host, the guests, and their three complexes, generated by Autodock Tools docking simulations, were reoptimized in both gas and implicit solvent phases using the DFT approaches as implemented in two quantum chemistry programs: Amsterdam Density Functional ADF2021. 107 program release  [48, 49]  and the Gaussian 09 program package  [50]. As implemented in the ADF program, the generalized gradient approximation (GGA) BLYP exchange-correlation density functional  [51, 52]  was used along with the Grimme's D3-BJ empirical dispersion correction  [53, 54]. The D3-BJ correction was used to improve the description of noncovalent interactions, i. e. , hydrogen bonding and van der Waals forces. Indeed, several previous post-Hartree-Fock (CCSD(T) and MP2) studies showed that dispersion corrections allow a better assessment of energies for noncovalent interactions  [41, 51].
For the ADF computations, the all-electron TZP basis set composed of triple-ζ Slater-type orbitals (STO) and augmented by polarization functions was used for all atoms. The solvent (chloroform) effects were introduced via the COSMO (Continuum Screening Model) method  [55]. This solvent was chosen due to the fact that it is often used for synthesis and characterization of such EtP5A complexes and various organic compounds  [14]. To ensure that the optimized structures are the real minima, vibration analysis based on the harmonic frequency approximation of the optimized structures was performed using ADF single-point calculations at the same BLYP-D3(BJ)/TZP level of theory. To elucidate the nature of the host-guest binding properties in such complexes, the analysis of the noncovalent interactions (NCI) combined with the index-reduced density gradient (RDG), commonly named the NCI-RDG technique, was carried using the MultiWfn program with larger size grids  [56] , and noncovalent interactions were depicted with the visual molecular dynamics (VMD) software  [57].
In order to gain further insights into the nature of bonding within the complexes and to examine the electronic features, the natural bond orbital (NBO)  [67]  analysis as implemented in Gaussian 09 program was carried out at the same level of theory for all optimized structures. Molecular orbitals (MOs) for the ground state structures were calculated with the implicit solvent effects included as well using the ωB97XD/6-311G* and B97D/6-311G* optimized geometries. Also, molecular electrostatic potential (MEP) was calculated with the implicit solvent effects included using the ωB97XD/6-311G* and B97D/6-311G* optimized geometries. Complex structures and MOs were visualized using OpenGL version of Molden 5. 8. 2 visualization software  [68]. Avogadro, version 1. 1. 1, was used to visualize the molecular electrostatic potential (MEP) maps  [69, 70].
In order to check this point, Basis Set Superposition Error (BSSE) calculations have been carried out using the Gaussian software at the ωB97XD/6-311G* level in the gas phase. The computed complexation energies with or without the BSSE corrections are reported in Table  5. From this latter table, it follows that taking Accepted manuscript / Final version into account the BSSE somewhat lowers the binding energy as usual, however, the binding trend remains the same as without BSSE. Notably, the BSSE corrections do not change significantly the energies.
3. 2. e. NCI-RDG analysis on the inclusion complexes The NCI-RDG analysis was carried out to visualize the nature of interactions between the EtP5A (host) and the three hydrocarbon molecules using the program MultiWfn with larger size grids  [56]. Figures  Typically, blue and green color regions are used to represent the stabilizing H-bonding and van der Waals interactions while red color region is used for the destabilizing steric interactions  [26, 56, 59, 60]. The interaction types are determined by analyzing the sign of λ2 which represents the eigenvalues of the Hessian of the electron density at the BCP (bond critical points). As reported by other authors  [75, 76] , for the bonding interactions such as H-bonding, the λ2 value will always be less than 0 while for the van der Waals type of interactions, λ2 ≤ 0.
Acknowledgments We acknowledge the Algerian  PRFU  project ( 2022-2024 : Grant No. B00L01EN250120220001 ) and the  French GENCI IDRIS  and  GENCI-CINES  for an allocation of computing time (Grant No. 2021-080649 ). Aleksey Kuznetsov appreciates the financial support of  USM  and computational facilities of the  Department of Chemistry, ITA, Brazil.
Objective: The anti-CD38 antibody Isa in combination with Kd is approved in various countries for patients (pts) with relapsed MM after ≥1 prior therapy, based on primary interim analysis (IA) of the Phase 3 IKEMA study (NCT03275285). Here we report updated efficacy and safety Results from IKEMA. Methodology: This prespecified final analysis (Isa-Kd 179, Kd 123 pts) evaluated updated PFS (primary endpoint), PFS2, CR rate, MRD-rate,.
Acknowledgements This work was partially supported by  Normandie Université (NU) , the  Région Normandie , the  Centre National de la Recherche Scientifique (CNRS) ,  Université de Rouen Normandie (URN) ,  INSA Rouen Normandie ,  Labex SynOrg  ( ANR-11-LABX-0029 ), the graduate school for research  XL-Chem  ( ANR-18-EURE-0020 XL CHEM ),  Innovation Chimie Carnot (I2C)  and the  Agence National pour la Recherche  ( ANR-CE07-0004-1 ). M. A. thanks the  Agence National pour la Recherche  ( ANR-CE07-0004-1 ) for a doctoral fellowship. This work is part of the  EFLUX program  supported by the  European Union  through the operational program FEDER/FSE 2014-2020. T. B. thanks the  Labex SynOrg  ( ANR-11-LABX-0029 ) and the  Région Normandie  for a doctoral fellowship ( RIN 50 % program ). P. J. and T.
The data analyzed using the software OMNIC Series 8. 2 from Thermo Scientific. Mechanical characterizations: Gel time experiment was performed at 1 Hz with a 20-mm plane-plane geometry on a ThermoScientific Haake Mars 60 rheometer equipped with a Peltier heating cell. A 30 mL h -1 nitrogen flux was applied. Stress relaxation experiments were performed on the same apparatus equipped with a textured 8-mm plane-plane geometry. A 10 % torsional strain was applied on 8 mm diameter and 2 mm thickness circular samples, and the rubbery modulus evolution with time was monitored. DMA: Dynamic Mechanical Analyses were carried out on Metravib DMA 25 with Dynatest 6. 8 software. Uniaxial stretching of samples (1 × 5 × 12 mm 3 ) was performed while heating at a rate of 3 °C min -1 from -90 °C to 150 °C, keeping the frequency at 1 Hz.
934 and 0. 989). A Kohlrausch-Williams-Watts "stretched exponential" equation was found to better fit (see Table S2 for the equation and the fitting parameters) the stress relaxation dataset 1 (R² between 0. 995 and 0. 99975, depending on the temperature). In KWW model, a stretch parameter β is added to the exponential decay. The closer to 1 is β, the closer to the Maxwell model are the data. From 170 °C to 210 °C, the value of β was about 0. 56±0. 02, indicating that the flow kinetics was associated with a distribution of relaxations rather than with a single relaxation time kinetics. 1 The relaxation time values obtained from the KWW fitting equations were plotted in an Arrhenius diagram (Figure 3 inset) to determine the value of the flow activation energy E a. This E a was determined to be 77 kJ mol in good agreement with the 29-163 kJ mol -1 range reported so far for transesterification vitrimers, 47  especially for catalyst-free vitrimers activated by neighboring groups for which the activation energy values are ranging from 78 to 94 kJ mol -59-61,.
Acknowledgements This work was funded by the  Institut Carnot Chimie Balard CIRIMAT  ( 16CARN000801 ) and the  French National Research Agency ANR  ( AFCAN  project  -ANR-19-CE06-0014 ). The authors would like to thank  Lise Reymond  for her contribution to TPE-TAF synthesis, as well as  Dr. Marc Guerre  and  Dr. François Tournilhac  for fruitful discussions.
The GC×GC was used with a temperature program starting at 40 °C, held for 2 min then heated up to 250 °C at 3 °C/min. The temperature of the secondary oven was set 5 °C higher than the primary oven, and the modulator temperature was set 5 °C higher than the secondary oven. The modulation period of the quad jet modulator was 4 s (consisting of 2 cycles with 1. 5 s of hot jet and 0. 5 s of cold jet). The mass spectrometer was used with electron ionization at 70 eV, using a scan range of m/z 45-300 at a scan frequency of 200 Hz. Data processing was handled using ChromaTOF software 5. 51 from LECO (Villepinte, France). All integrations were made on the most abundant m/z for each compound. The ChromaTOF software automatically integrated peaks on the 1D chromatogram with a "target analyte finding" method (TAF), followed by a manual checking For validation tubes, methane was used as the carrier gas instead of helium.
The GC×GC was used with a temperature program starting at 40 • C, held for 2 min then heated up to 250 • C at 3 • C/min. The temperature of the secondary oven was set 5 • C higher than the primary oven, and the modulator temperature was set 5 • C higher than the secondary oven. The modulation period of the quad jet modulator was 4 s (consisting of 2 cycles with 1. 5 s of hot jet and 0. 5 s of cold jet). The mass spectrometer was used with electron ionization at 70 eV, using a scan range of m/z 45-300 at a scan frequency of 200 Hz. Data processing was handled using ChromaTOF software 5. 51 from LECO (Villepinte, France). All integrations were made on the most abundant m/z for each compound. The ChromaTOF software automatically integrated peaks on the 1D chromatogram with a "target analyte finding" method (TAF), followed by a manual checking.
Charge-transfer evaluation was carried out via electrochemical impedance spectroscopy (EIS) from 50 kHz to 10 Hz, at a sinusoidal potential of 5 mV, with zero supplied potential, at room temperature, in 0. 1 mM uric acid prepared in 0. 01 M phosphate buffer solution at pH 7. 4. Z-view soware was used to t the experimental data to an equivalent circuit to check the reliability of the measured data.
The 51 V MAS NMR spectrum was acquired in a Bruker DSX 300 spectrometer ( 51 V: 78. 9 MHz) using a single pulse excitation. The signal was optimized with crystalline V 2 O 5 (δ = -609 ppm) as external standard with a pulse angle of π/2. Two spinning rates were used to determine the isotropic chemical shift (10 kHz and 12 kHz). Xray absorption spectra were acquired at ESRF on BM23 beam-line, at room temperature at the vanadium K edge. A double crystal Si(111) was used as monochromator and a system based on a total reflection through a double X-ray mirror with an incidence angle variable from 2 to 5 mrad allowed harmonic rejection to better than the 10 -5 level. [21]  The spectra were recorded in the transmission mode between 5. 4 and 5. 65 KeV at room temperature (295 K). Each data set was collected simultaneously with a V metal foil reference and was later aligned according to that reference (first maximum of the derivative of the V foil spectrum set at 5465.
Acknowledgements This work was carried out as a part of  BIZEOLCAT  project, which has received funding from the  European Union 's  Horizon 2020 Research and Innovation Program  under grant agreement No. 814671. In particular, J. A. N. is grateful for her PhD grant. AdM thanks  Olivier Mathon  and  Kiril Lomachenko  for their help during the recording of the X-ray absorption spectra at  ESRF , on beam line BM23.
Computational details We have performed ab initio calculations by means of density functional theory (DFT) with the projector augmented wave (PAW) method  33  as implemented in the Vienna Ab initio Simulation Package (VASP). 34 For the exchange and correlation contributions, the Perdew-Burke-Ernzerhof (GGA-PBE) functional  35  was employed with a kinetic energy cutoff of 450 eV for the plane wave basis set. The D2 dispersion correction of Grimme was used to describe dispersion interactions. 36, 37 Also, the rev-vdW-DF2 approximation is used where the revised Becke exchange functional (B86R) is adopted for the exchange functional together with the second version of nonlocal vdW-DF. 38 The goal here is to be able to compare the two levels of theory to consolidate our prediction. Regarding the large size of the used unit cell, the calculations were performed with the G-point.
Isothermal Titration Calorimetry Experiments ITC measurements were performed with a VP-ITC microcalorimeter (Microcal, GE-Healthcare). Experiments were carried out in water and in a solution of K 2 HPO 4 (1. 5 mM) in mili-Q water at 298. 15 ± 0. 1 K. Anion binding to BU was investigated via a classical isothermal titration experiment (10 µL additions) and a single injection method (SIM). Injection of sodium iodide solution was added automatically to the BU solution present in the calorimeter cell while stirring at 307 rpm. Integrated heat effects were analyzed by nonlinear regression using a single-site binding model (Microcal  Origin 7). The experimental data fitted to a theorical titration curve, giving the association constant K a , the enthalpy of binding ∆H • and the entropy ∆S •. The free energy ∆G • was calculated from the equation: ∆G • = ∆H • -T∆S • , where T is the absolute temperature.
Acknowledgments: We thank  J. Rivollier  ( Université Paris-Saclay/CEA/DMTS/SCBM ) for preliminary neoglycoBUs synthesis. Y. Boulard  ( Université Paris-Saclay/CEA/I2BC ) and  F. Fenaille  ( Université Paris-Saclay/CEA/DMTS/SPI ) are thanked for recording 600 MHz NMR spectra and for mass spectrometry experiments, respectively.
X-ray and 2D-NMR Analysis of Compound 9. Compound 9 was recrystallized in methylene chloride. The obtained single crystals, which appeared as purple platelets, were analyzed by X-ray diffraction (Figure  3 ). Mo-Kα radiation was used, and the compound showed a P2 1 /n space group (crystallographic Data in the Supporting Information). Inspection of the structure Compound 9 was also analyzed by 2D-NMR at 298 K. All the 1 H and  13  C signals were assigned based on the chemical shifts, spin-spin coupling constants, splitting patterns, and signal intensities and by using 1 H-1 H COSY45, 1 H-13 C HSQC, and 1 H-  13  C HMBC experiments (see the Experimental Section). In addition, the attribution of C4 and C9 of compound 9 was based on the previous study of Borgati et al. ,  40  where the authors performed a complete, comparative 1 H and  13  C signal assignment of p-naphthoquinones and ortho-and paranaphthofuroquinones.
falciparum. 26 he AlphaFold2-modeled structure of the cytochrome enzyme (Q7HP03) was used to characterize the predicted interactions between the compounds described and the P. falciparum target bc1. 49 All local quality measures of the predicted protein structure were assessed as very good (Figure  6 ), that is, per-residue confidence scores (pLDDT) for the model were all very high near the binding site region (central groove inside the α-helices, near Tyr 263) and had low expected position error (dark green in Figure  7 , in angstrom) for the predicted alignment errors (PAE), that is, the values for expected position error at residue x when the predicted and true structures are aligned on residue y. For the DHODH target, the X-ray crystal structure of Pf DHODH (Protein Data Bank (PDB) 7l)  50  was retrieved from the PDB having a resolution of 1.
Gradient-enhanced HMBC experiment was performed, allowing 62. 5 ms for long-range coupling evolution (64 scans were accumulated). Typically, 2048 t2 data points were collected for 256 t1 increments. Computational and Docking Experiments. The Alpha-Fold2-predicted structure of the protein Pf bc1 was downloaded from the European Bioinformatics Institute website 62 and preprocessed with PrepWizard [Schrodinger LLC. 2021] to add hydrogens, minimize the structure, and resolve the ionization states and clashes. The binding site was specified in analogy to the structure 4pd4 from the PDB. 63 he X-ray crystal protein structure (7l01, resolution = 1. 60 Å) for Pf DHOHD was downloaded from the PDB  63   Chemical compounds were imported as SMILES or drawn, energy-minimized with Maestro [Schrodinger LLC.