EMBO/sd-character-level-ner huggingface dataset:
Spearman correlation between the expression level of a gene and its major PAS usage for genes with different major PAS location. P values were obtained from binomial tests to examine whether the number of genes with positive correlations is larger than the random expectation of 50%: ***P < 0.001. Upstream: upstream of last stop codon, 3' UTR(S): the only PAS in the 3' UTR, 3' UTR(F): the most proximal PAS in the 3' UTR, 3' UTR(M): the middle PAS in the 3' UTR, 3' UTR(L): the most distal PAS in the 3' UTR. The boxplot shows the Q1 to Q3 quartile values (the box limits), the median (the horizontal green line) and values within the 1.5 * IQR (the whiskers).
(G) Confocal microscopy analysis of paired normal and carcinoma tissues from two colon cancer patients. The frozen sections were incubated with rabbit anti-AnnexinA1 polyclonal antibodies and 5G11 mouse anti-FadA monoclonal antibodies. The slides were then stained with Alexa Fluor®680-conjugated donkey anti-rabbit and Alexa Fluor®555-conjugated goat anti-mouse, washed, and covered in mounting medium containing DAPI. The scanning confocal microscopy mages were taken with a Nikon Ti Eclipse inverted microscope at 200x magnification for the normal tissues and 400x for the carcinomas. Scale bar, 50 μm. Co-localization of FadA (red) and Annexin A1 (green) was observed in carcinomas but not in the paired normal tissues.
16-days old MCF10A spheroids grown in matrigel/collagen mix were stimulated for 24h with either macrophage-conditioned or control medium in presence of NCT502 (10 μM). NCT502 reduces the filling of the spheroid lumen with cell nuclei. Filling of the spheroid lumen with cell nuclei. Partially filled, almost filled and filled spheroids were combined together (non-empty spheroids). Macrophage donors are indicated as D1-D25. M1D - M1 differentiated, M1A - M1 activated, M2D - M2 differentiated, M2A - M2 activated macrophages.
(P) Hierarchical clustering and heatmap of the expression level of DEGs belonging to the "neuron differentiation" Heat map color scale indicates normalized gene expression from high (red) to low (white) level. Data information: For statistical analysis of RNA-Seq data see Methods.
The Dyf phenotype of the ts-che-3 mutant was confirmed, with animals grown at the permissive temperature (15ºC) showing the ability to uptake dye, while those raised at the restrictive temperature (25ºC) are Dyf. Scale bar, 20 µm
E. Quantification of relative protein glycosylation of the data shown in C (n = 3). Data are represented as mean ± SEM. ***p<0.001 (Student's two-sample t-test)
B. Scatter plot of the normalized mean cell length and mean cell width of all 4,227 Keio strains and 240 WT replicates. Each dot represents a strain, and the gray level illustrates the density of neighbors in the vicinity of each point in the graph. The dotted contours represent the 0.5, 0.75 and 0.95 probability envelopes of the 240 WT replicates. The correlation between mean cell width and mean cell length is low (ρ = 0.06, 95% CI [0.03, 0.09]).
Anti-Flag signals in (C) were quantified, and relative signal intensities are presented. The value of the WT Rab8a signal with MG-132 was defined as 1.0. Note that all signal intensities of Flag-tag were normalized by that of the Rab8a input signals.
(A) The positions of M1190D, c.3610C>T (p.R1204X), and c.3636+1G>T (p.A1211VfsX22), with the latter being the only mutation previously associated with DFNA1. Bidirectional arrow shows the autoinhibitory intramolecular interaction between the diaphanous inhibitory domain (DID) and the diaphanous autoregulatory domain (DAD). GBD; GTPase-binding domain, FH1 and FH2; formin homology domain 1 and 2.
A Relative abundance of mRNA for the indicated xenobiotic stress response gene (or UbG76V-GFP or mRFP) detected in wild type versus dop-1 mutants. Values are based on RNA-seq/EdgeR analysis, with the relative levels for each gene normalized to the value observed in the wild-type control. ****P<0.0001, **P<0.01, *P<0.05 FDR from EdgeR analysis using a Benjamini and Hochberg correction.
(D) HEK293T cells co-transfected with HA-tagged p38IP, Flag-tagged TAB2-ub, together with cMyc-tagged TAK1 (open arrow) or ub-TAK1 (solid arrow), were lysed and immunoprecipitated with anti-cMyc, and then immunoblotted with the indicated antibodies. The relative intensity of the IP bands was quantified by densitometry and is presented in the right.
E. 1/αRRA scores from two biological replicates of the genome-scale screen. Dotted lines represent the significance cut-offs for each replicate. Genes identified as significant in both screens are highlighted.
E. Purified recombinant WT or 3A INVS were generated (top panel, lanes 1-4). In IVK, Akt phosphorylated the WT fragment (824-898, middle panel, lane 3), but failed to phosphorylate 3A INVS (middle panel, lane 4), as detected by using a phospho-Akt substrate antibody.
B Immunoblots showing the levels of the indicated proteins in different types of HER2+ breast cancer stably expressing CDK12 or with CDK12 knocked down. Cell line information: a/a, CDK12-amplified/HER2-amplified cells; n/a, CDK12 non-amplified/HER2-amplified cells; R, trastuzumab-resistant; PR, trastuzumab-partial responsive; S, trastuzumab-sensitive.
(a) Outline of the screening strategy. MS, mass spectrometry. See the text for details.
B Quantification of normalized pPDH/PDH levels calculated from fluorescence intensities in macrophages from the genotypes in (A) during initial germband invasion. The pPDH/PDH ratio is significantly increased in atosPBG embryos expressing either pths, GR/HPR, or LKR/SDH in macrophages compared to the atosPBG embryos. This argues that the decreased Atos function in atosPBG macrophages, resulting in lower cellular ATP/ADP ratios, was restored by expressing either its targets or murine orthologs. N=3 independent experiments. Control (n=9 embryos) vs. atos mutant (n=10) p<0.0001. Control vs. atos mutant rescued with mac>pths (n=10) p=0.77; rescued with mac>GRHPR (n=9) p=0.48; rescued with mac>LKRSDH (n=10) p=0.012. For atos mutant vs. atos rescued with mac>pths or mac>GRHPR p<0.0001. vs. atos rescued with mac>LKRSDH p=0.0014. Data information: Mean±SEM, ns=p>0.05, *p<0.05, **p<0.01, ****p<0.0001. One-way ANOVA with Tukey
(C) AEP activity assay with colon lysates from DSS-treated mice. Data represent the mean ± SEM; representative data of three samples; ***P = 0.0002 (*** P ＜ 0.001), **** P ＜ 0.0001 compared with control, one-way ANOVA. (D) AEP activity assay with brain lysates from DSS-treated mice. Data represent the mean ± SEM; representative data of three samples; *P =0.0103 (*P< 0.05), ****P < 0.0001 compared with control, one-way ANOVA. (E) Gastrointestinal permeability barrier defect as determined by FITC-dextran translocation in DSS-treated mice. Data represent the mean ± SEM; representative data of three samples; **P =0.0071 (**P < 0.01)，***P =0.0009 (3xTg vs 3xTg AEP KO) , ***P =0.0004 (3xTg vs WT) (***P < 0.001) compared with control, one-way ANOVA. (F) Human Aβ1-42 concentration in brain lysates from DSS-treated mice. Data represent the mean ± SEM; representative data of three samples; **P=0.0097(**P< 0.01), ***P =0.0006 (***P < 0.001) compared with control, one-way ANOVA.
C. DRIP-qPCR for R-loops around the engineered +3.5 (GAA) 10 repeat in BU-1 in different phases of the cell cycle. The location of the qPCR amplicons is indicated in the map at the top of the panel. The BU-1 DRIP signal was normalised to -0.5 kb amplicon in G1-arrested cells (t = 0 h) Black: wild type; red: primpol. Error bars = SD. **** p ≤ 0.0001, *** p ≤ 0.001, ** p ≤ 0.01, * p ≤ 0.05
A: Diurnal behavior in the home cage (HC). NexCre cTKOs show overshooting activity in the dark phase. Line graphs illustrate the average locomotion per hour. [Sidak's multiple comparisons test, geno F(1,32) = 9.503, p = 0.0042; timepoint F(6.102,195.3) = 10.51, p < 0.0001; timepoint × geno F(47,1504) = 5.874, p < 0.0001].
E The negative regulation of cell adhesion correlates with the amount of released SMB. Scatter plot showing the correlation between the reduction in cell adhesion (panel C and Appendix Fig S7C) and SMB release (panel A and Appendix Fig S7B). The extent of cell adhesion reduction was calculated at the indicated time point in panel C as percentage of the cell index value measured in control wells treated with vehicle. Samples size (n), Pearson correlation coefficient (r) and p-value are reported.
Freezing phenotype (A) of the egr2-3 mutant and egr2/EGR2:EGR2-Myc complementation lines under non-acclimated (NA) and acclimated (CA; 4 d at 4°C) conditions. Two-week-old seedlings grown on MS medium containing 0.8% agar were treated at −5°C for 0.5 h (NA) or −8°C for 0.5 h (CA).
Sex chromosome recombination was perturbed in 6-month-old Usp26-/Y mice. Immunofluorescence analysis of SYCP3 (green), MRE11 (red) (G); was performed in 6-month-old Usp26+/Y and Usp26-/Y spermatocytes. Nuclei were stained with DAPI (blue). The arrows indicate the sex chromosomes.
Liner fit of EdU and Ki67 double positive NSC ratio for 6 hours cumulative EdU incorporation. ShRNA-Scrb: y =9.21x + 23.23; shRNA-Rgcc: y =7.98x + 16.46. At least 3 brains were taken for each time points/group.
(C) Following recruitment by Ras-GTP, B-Raf forms homo- or heterodimers with the assistance of 14-3-3 proteins. This loosely dimerized and membrane-bound state is imitated by the B-RafE586K and B-RafCAAX mutants, which still require an intact DIF and AL phosphorylation. Within the dimer, one protomer becomes phosphorylated at its TVKS-motif in cis (depicted by black bent arrow) leading to re-orientation of the DIF and induction of a conformational change in the other protomer (blue bent arrow) followed by phosphorylation of the AS in the other protomer in cis. B-RafV600E is locked in the highly active state and thus signals independent of an intact TVKS-motif or DIF. See text for further details.
H&E staining (A) and histogram of the HF length (B) in adult back skin sections from Prox1CreERT2+/+; LSL-ROSA26-iDTRKI/KI mice injected with vehicles (Control), Prox1CreERT2+/T; LSL-ROSA26-iDTRKI/KI mice treated with CSA and vehicle (CSA); and Prox1CreERT2+/T; LSL-ROSA26-iDTRKI/KI treated with tamoxifen, CSA and intradermal Diphtheria Toxin (CSA+DT) starting from early Telogen (P49) and analyzed at the end of the treatments (P58). n= 3 - 4 skin samples per mouse, n= 3 - 4 mice.
(A) Immunoblots for mitochondrial ferritin (FTMT) with HSP60 as the loading control using the mitochondrial fraction of Huh7 cells and HepG2 cells (upper panels) and the quantification of mitophagy using mt-mKeima transfection and FACS analysis (n=4, biological replicates) (lower panels) before and after DFP (1.0 mM) treatment with or without FTMT knockdown by siRNA. The central horizontal bar and the error bards indicate mean ± SD. The Tukey's honestly significant test was used for statistical analysis. NC: negative control siRNA, **: P<0.01.
A Periodic measurement of the oxygen consumption rate (OCR) of mitochondria, isolated from 5 mice per genotype, before and after the administration of the indicated compounds (left). Quantification of OCR in independent experiments, n= 8 per genotype (right).
(L) The effect of overexpression of ABCA1 and ABCG1 on GSIS from MIN6 cells with ABCA12 deficiency (mean±SEM, n=4 (biological replicates assayed in triplicate), *p=<0.05, Students t-test).
H. Phos-tag band-shift assay of Hog1 phosphorylation. The yeast strain FP4 was transformed with the single-copy expression plasmid pRS416-Hog1 (WT) or pRS416-Hog1-ΔL16, and was treated with the indicated concentrations of NaCl for 5 min. The averages of three independent experiments are shown. Data information: Error bars are SEM (n=3).
A. Ingenuity Pathway Analysis of differential gene expression (fold-change (FC) > 1.5, p < 0.05) in wt and Sharpincpdm MSFs (passage 0). The differentially expressed genes implicated in the most significantly altered canonical pathways (leukocyte adhesion and transmigration, and tissue fibrosis) are shown. Three independent cell isolation replicates were compared pairwise. FC colour scale represents a range from 0−4.
F) Immunoprecipitation and Western blot were performed in HFFs with and without IFNγ (10 U/ml) using a RH+GRA15WT, RH+GRA15TRAF2mut or RH+GRA15TRAF2/6mut. For the unstimulated cells, uninfected HFFs were used an additional negative control (left panel). Left panel and right panel were run on a single gel; vertical white lines indicate excision of irrelevant lanes. Full length blots are in the source data for this figure. The antibodies used against TRAF2 and TRAF6 were purchased from Cell Signaling Technology and Abnova, respectively. The asterisks (*) in the lower right panel indicates the faint band of TRAF6 in the RH+GRA15TRAF2mut immunoprecipitate.
F Immunoblot analysis of HeLa cells that were transfected with siRNA oligonucleotides directed against a non-relevant mRNA (Ctrl) or against Xiap mRNA and treated with taxol as specified.
D Sox2 mRNA expression upon CsA (1 μM) treatment in L3.6 cells (adherent versus spheres) (*P 0.05).
U87 cells were treated with DMSO or LXR623 20 µM for 24h. Thereafter, cells were processed for polar metabolite analysis by LC/MS. In panel A, -log10 p-values and log2 fold change (fc) are shown. Highlighted in red are TCA - cycle related metabolites. In panel B, metabolite pathway analysis was performed. Highlighted (red dots) are the tricarboxylic acid cycle and pyruvate metabolism as significant and impactful pathways altered by LXR623 treatment.
(C-D) Same as panels A-B, but with pairs of loci labeled with YFP-ParBpMT1/parSpMT1 and mCherry-ParBP1/parSP1 at genomic positions 1400 and 1600 kb (inter-domain) or at 1600 and 1800 kb (intra-domain). Note that differences in Hi-C chromosomal domain sharpness reflect differences in interaction patterns as the color scale and image contrast settings are identical across each time series.
A. The indicated recombinant INVS proteins (lanes 1-4) were used for IVK. Akt phosphorylates WT (lane5), 1-970 (lane 6), and 1-898 (lane 7) INVS, but failed to phosphorylate 1-670 (lane 8) INVS.
(A) Western blots show the knock-down efficiency of shFNTA in J82 and UMUC3 cells.
786-0 cells expressing WT or ED GDH1 were supplemented with or without 500 μM methylated αKG for 36 hours, and then cells were collected to extract total mRNA. The mRNA levels of the indicated RP genes were tested using qPCR (D)
EMT-related markers, stemness markers and drug resistance genes were assessed by WB (D) in SNU719 and YCCEL1 cells transfected with circLMP2A or vector.
(a) IB3-1 cells cultured with 250 μM cystamine or transfected with either 50 nM human TG2 siRNA or scrambled oligonucleotides. IP, immunoprecipitation; IB, immunoblot.
D Gene expression-based classification reveals that SSAs could progress to CMS1 and CMS4 tumors. The data presented in this manuscript suggest that high activity of the TGFβ signaling pathway directs these precursor lesions to the CMS4 of CRC.
J. Quantification of the percentage of dead cells six days after MDGI silencing and LGALS1 staining (n = 100) in control (Scr) and MDGI-silenced (sh1) BT12 and BT13 cells. Data are represented as mean ± SD. **P < 0.01, two-tailed, nonparametric Mann-Whitney's U-test.
F) Size of schizonts in Z1/hGK++/hGS-, Z2/hGK+/hGS- and Z3/hGK-/hGS+ hepatocytes on day 3 post invasion for the different Pf strains. For each parasite line, at least 100 schizonts were measured from each biological replicate. The median values +/- s.d. (as the sizes within the population is not normally distributed) from three biological replicates were used in a RM ANOVA test followed by a Tukey's multiple comparison test. Data information: * p <0.05; ** p < 0.005; *** p <0.001; **** p <0.0001
Scanning electron micrographs of the ependymal surface of the lateral ventricle of CWH43 WT and CWH43M533/M533 mice. Scale bar is approximately 40 µm. The graph on the right quantifies the data from the electron micrographs on the left. Data shown are the mean ± SEM. * = P=0.004, n = 4, unpaired t-test.
CNET-plot (derived from analysis shown in D) illustrating genes involved in tuberculosis and phagosome KEGG pathways.
C Hsf1(1-408) with a deleted TAD is dissociated from HSE-DNA by Hsc70, DnaJB1 and ATP with similar rates as Hsf1wt. Fluorescence polarization assays containing Alexa Fluor® 488-HSE-DNA bound Hsf1(1-408) trimers and the indicated components.
(C) Heatmap of differentially methylated uniquely mapped 500 bp tiles. Shown are random 20% of all significantly hypo- (450 of 2253) and hyper-methylated (2063 of 10316) tiles (logistic regression function of Seqmonk, padj< 0.01, difference 20%, for details see method section).
G) Scatter plot showing genes for which a significant effect of treatment with steroids. The group effects at baseline are plotted on the x-axis, while the effects of steroids are plotted on the y-axis.
(a) Fbxo7 relocates from the cytosolic to the mitochondrial fractions of HEK293T cells treated with CCCP (10 μM). IB, immunoblot.
G. Recruitment of IN1 along the SCR1 gene locus. Top. ChIP‐qPCR analysis as described for panel Fig 3B. Data represent means ± SD (n = 3). Bottom. Schematic representation of the SCR1 locus with DNA amplicon positions. TATA, A and B boxes and terminator of transcription (T) are indicated.
A. Representative FACS profiles of HSPC cell cycle analysis using combinatorial staining for Ki67 and Hoechst 33342. Bar charts depict the average percentage of cells in each phase of the cell cycle for each LSK subset from WT (n=6) and PKCδ KO (n=7) mice. Data compiled from two independent experiments. Data information: All data are presented as mean±SEM, *p<0.05 and **p<0.001, with significance determined by two-tailed Student's unpaired t-test analysis.
a) Experimental design for miR-29a mimic treatment in young mice. Primary visual cortex (V1).
Alignment (the right panel) shows amino acid sequences of the C-terminal tail of Fis1 from the indicated organisms: human (h), mouse (m), rat (r) and S. cerevisiae (y); red letters mark the lysine residue required for Fis1 SUMOylation. Schematic (the left panel) illustrates SUMO conjugation at the C-terminal tail of Fis1 (N, N-terminus; TM, Transmembrane domain; C, C-terminus).
E SUMOylation of ETS-4 in mammalian cells. HEK293 cells were transfected with plasmids encoding HA-ETS-4 (WT), HA-ETS-4(K32A; K83A) (2KA), T7-TDPT-1, His-SUMO-1, His-SUMO-2 and Myc-MXL-1, as indicated. SUMO-conjugated proteins were isolated by cobalt affinity chromatography. ETS-4 was detected by immunoblotting with anti-HA antibody. Whole-cell extracts (WCE) were analyzed by immunoblotting (IB).
H. For the in vitro ubiquitination assay, purified PSMA2, tagged and immunopurified FBXO7 and SCF core components from HEK293T cells, E1 enzyme, ubiquitin and ATP together with indicated E2 enzymes were incubated for 1 h at 37 °C. The reactions were immunoblotted with the PSMA2, ubiquitin or FBXO7 antibodies.
c) Regions of 1H-15N-HSQC-TROSY spectra of UbcH7-O-15N-Ub in the absence (black) and presence (red) of a RING1 domain from the RBR E3s HHARI (left) or RNF144 (middle) or a canonical RING domain of BRCA1/BARD1 (right). The perturbations on Ub due to binding of HHARI RING1 and RNF144 RING1 are remarkably similar, while binding of the canonical RING domain of BRCA1/BARD1 has no observable effect on the Ub spectrum. Gray boxes mark area expanded in a)
A Overabundance of histamine in Tsc2 wild-type relative to Tsc2-deficient MEFs, both growth in DMEM 10% FBS. The asterisks indicate significant difference with two-sided t-test (P = 0.017); replicates/condition n = 5, and independent experiments n = 2). Average values are indicated with lilac-colored lines.
H. Rabl2Q80L inhibited Hh signaling. MEFs from Rabl2-/- E12.5 embryos infected with lentivirus to express GFP, GFP-Rabl2 or GFP-Rabl2Q80L were serum-starved for 24 h and treated with DMSO (mock) or 100 nM SAG for an additional 24 h. Uninfected MEFs from the wildtype littermate embryos served as the positive control. The samples were immunoblotted to examine levels of Gli1 and Gli3 In the samples for immunoblotting (H), GFP-positive cells occupied 82.3% (GFP), 87.3% (GFP-Rabl2), and 81.2% (GFP-Rabl2Q80L), respectively, when 260 cells in each sample were scored. Relative band intensities are shown in red.
Quantification of GFP+ cells among CD45+CD11b+ retinal microglia by flow cytometry. Data are presented as mean ± s.e.m. One symbol represents one mouse.
(D) Assay of HOIL-1[Δ194-222] lacking the NZF core domain at 30°C in the absence or presence of the indicated ubiquitin oligomers.
(A) Spot assays on solid media from a three-fold dilution series of exponential cultures at the same cell density in 96-well plates (3 biological replicates of each strain) and spotted in 16 technical replicates (each dilution in 4x4 square). The A-strain is more resistant to antimycin A but less resistant to oxidative stress triggered by H2O2 or diamide. A control without toxin (left) was included in each batch of spot assays performed and a representative image is shown here.
(C) Primary lung resident fibroblasts isolated from TGFα mice on Dox for 4 wks were treated with vehicle or 5µM barasertib for 48hrs and immunostained using PCNA antibody. Images were obtained at 40X magnification. Scale bar: 50µm. The number of PCNA-positive cells and total DAPI-positive cells were quantified using MetaMorph image analysis software. Proliferation is indicated as the percentage of proliferating cells in total DAPI-positive cells. ****P < 0.00005, unpaired t-test, (n=3-4).
Mice (n=6-10/group) underwent a sham (with or without starvation) or CLP operation and blood was collected 6h and 24h post-surgery. Normalized abundances of (H) palmitic acid and (I) palmitoyl-carnitine determined via liquid chromotography-mass spectrometric lipidomics. Values were normalized to IQ values , P-values were calculated with 2-way ANOVA tests. n = 8/group.
(A) Targeting strategy. Top: Targeting vector pSC-floxAVKA and a part of the murine Braf locus containing exons E14-E16 (not drawn to scale). Middle: Braf locus after homologous recombination with the targeting vector replacing E15 with a loxP-flanked (floxed) minigene (MG; E15-20) segment. pA = polyadenylation signals; SA = splice acceptor. LoxP and Frt sites are indicated by red triangles and blue hexagons, respectively. Bottom: The modified Braf locus after Flp-e and Cre mediated recombination.
G H2 consumption by S. sonnei. Bacteria were grown aerobically in LB overnight then diluted into M9 minimal media supplemented with 0.5% fumarate, 12.5 μg/ml nicotinic acid and 0.2% casamino acids in a sealed glass chromatography vial. The headspace was purged with 10% H2/90% argon and cultures were incubated at 37 °C with shaking at 180 rpm for 9 hours. H2 in the headspace was sampled and measured by gas chromatography.
A, Wildtype or kit mutant stained with AFOG at 14 days and 30 dpi. Sham-operated zebrafish hearts serve as control. Scale bar = 100 μm.
(L) Immunofluorescence images from mitotic Ctr and DIA treated B1dd/B2ko cells after P/A synchronisation stained with anti-alpha-tubulin (green), anti-gamma-tubulin (red) antibodies and DAPI (blue), scale bar = 5µm. Cells were exposed to ice-cold medium and either fixed immediately after cold exposure, or incubated for 5,10, or 20 minutes at 37° C before fixation.
(O and P) Inhibiting acetyltransferases CBP/P300 by TPOP146 (134 nM) or PCAF by L-45 (126 nM) for 24 h did not significantly decrease the K49-acetylated β-cat level in Tau-overexpressing N2a cells (n=3 biological replicates each group). Data information: Data are presented as mean ± SEM; *, P<0.05; **, P<0.01; ***, P<0.001 vs Vec Data were analyzed by one-way ANOVA
Heatmaps of ATAC-seq, anti-GFP (GFP-UBR7) ChIP-seq, and anti-H3K4me3 CUT&RUN in parental and UBR7KO cells. Plots are centered on TSS that­­­­­ show changes in ATAC-seq signal in UBR7KO versus parental cells. Sites are clustered by unsupervised k-means analysis. Cluster color key is defined by cluster labels.
FOXA2 and FOXA1 expression in wild type and genome-edited high-grade PANC1 cells. Three different bulk populations were used for RNA-seq experiments.