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Influence of different light qualities on chlorophyll concentrations of mung bean sprouts (mg/g DW). Mung bean seeds of three cultivars were germinated and grown under dark or light conditions for 6 days. “-1” and “SH1” means Su Huang No.1, “-5” and “ZL5” means Zhong Lv No.5, “-13” and “ZL13” means Zhong Lv No.13; “CK” means dark control, “WL” means white light, “BL” means blue light, and “RL” means red light. Results are presented as mean ± SD (n = 3). Different letters indicate significant differences (p < 0.05) between values.

PMC10025981

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Influence of different light qualities on carotenoid compositions and concentrations of mung bean sprouts (μg/g DW). Mung bean seeds of three cultivars were germinated and grown under dark or light conditions for 6 days. “SH1” means Su Huang No.1, “ZL5” means Zhong Lv No.5, “ZL13” means Zhong Lv No.13; “CK” means dark control, “WL” means white light, “BL” means blue light, and “RL” means red light. Values are presented as mean ± SD (n = 3).

PMC10025981

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Influence of different light qualities on tocochromanol concentrations of mung bean sprouts (μg/g DW). Mung bean seeds of three cultivars were germinated and grown under dark or light conditions for 6 days. “SH1” means Su Huang No.1, “ZL5” means Zhong Lv No.5, “ZL13” means Zhong Lv No.13; “CK” means dark control, “WL” means white light, “BL” means blue light, and “RL” means red light. Results are presented as mean ± SD (n = 3).

PMC10025981

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Related gene expression levels of carotenoid and tocochromanol biosynthesis pathway in mung bean sprouts exposed to dark or different light quality treatments. The values show the expression relative to Actin as means ± SD (n = 3). HPP, 4-hydroxyphenylpyruvate; HGA, homogentisic acid; MBPQ, 2-methyl-6-phytylbenzoquinol; DMPBQ, 2,3-dimethyl-5-phytylbenzoquinol; DXP, 1-deoxy-d-xylulose 5-phosphate; MEP, methylerythritol phosphate; IPP, isopentenyl diphosphate; PDP, phytyl diphosphate; GGDP, geranylgeranyl diphosphate; MGGBQ, geranylgeranyl-2-methylbenzene-1,4-diol; DMGGBQ, 6-geranylgeranyl-2,3-dimethylbenzene-1,4-diol; DXS, 1-deoxy-d-xylulose 5-phosphate synthase; DXPR, 1-deoxy-d-xylulose-5-phosphate reductase; HPPD, 4-hydroxyphenyl-pruvate dioxygenase; GGPPS, geranylgeranyl diphosphate synthase; HPT, homogentisate phytyltransferase; MPBQ-MT, MPBQ methyltransferase; TC, tocopherol cyclase; TMT, tocopherol methyltransferase; PSY, phytoene synthetase; PDS, phytoene desaturase; Z-ISO, ζ-carotene isomerase; ZDS, ζ-carotene desaturase; CRTISO, carotene cis–trans isomerase; LCYE, lycopene ε-cyclase; LUT5, β-ring hydroxylase; LUT1, carotenoid ε-hydroxylase; LCYB, lycopene β-cyclase; CHYB, β-carotene 3-hydroxylase; VDE, violaxanthin de-epoxidase; ZEP, zeaxanthin epoxidase; D27, beta-carotene isomerase D27; XDH, xanthoxin dehydrogenase; ABA, abscisic acid.

PMC10025981

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Pearson correlations between compounds and gene expression in the synthesis pathway of (A) tocochromanols (B) carotenoids. Colored circles represent correlation is significant at the 0.05 and 0.01 levels. The number of samples used for correlation analysis was 36, including 3 replicates of each genotype.

PMC10025981

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2a18b09e14ef4387a4b939e8315b9b6d

The relationship between whether there was a storm in the 48 hours prior to capture (yes, darker shade; no, lighter shade) and (A) fat mass, (B) total body water, (C) lean mass and (D) hematocrit of male (blue) and female (grey) grasshopper sparrows (A. savannarum, n = 325 for A, B and C, n = 263 for D). The black points represent the mean and the whisker represents the standard deviation for each sex.

PMC10026549

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The relationship between the average wet bulb temperature (°C, wet bulb temperature is an index of temperature and humidity) in the week prior to capture and the fat mass (g) of grasshopper sparrows (A. savannarum). Each point represents one individual (n = 325).

PMC10026549

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a654e858b9a54f59a332b888a9e4bcf9

Schematic of sample acquisition for analysis.A) CD90 positive mesenchymal stromal cells isolated from breast cancer patients express a unique gene expression profile indicative of increased cell to cell signaling. MSCs were isolated from fresh stromal tissue adjacent to an invasive lesion (tumor-associated) or distal to the tumor site (patient-normal). B) Microscopy images demonstrating phenotypic characteristics of CD45+ or CD45-/CD90+ cells isolated by magnetic-activated cell sorting (MACS). C) CD90+ cells were subjected to FACS for phenotypic mesenchymal associated cell surface markers. D) Microscopy images demonstrating tumor tissues used for FFPE gene expression analysis. Hematoxylin and Eosin staining of tissue sections used for analysis (left panel) and images of tumor sections before and after Laser Capture microdissection (LCM) (right panels).

PMC10027225

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Gene expression analysis of patient-derived stromal and tumor samples.A) Principal component analysis (PCA) of gene expression profiles from MSCs isolated from patients. PCA of 35,264 transcripts expressed in MSCs isolated from unaffected young individuals (normal), unaffected tissue from breast cancer patients (PNS), or patient tumor stroma associated sites (PTS). Gene signatures in CD90+ MSCs from breast cancer (BC) patients are sufficient to distinguish between breast cancer patients and healthy individuals as well as tumor associated site and unaffected site. B) Scatterplot of gene expression demonstrating that tumor-associated MSCs (PTS) demonstrate gene expression changes compared to a distal site (PNS). C) Heatmap demonstrating trends in expression of 133 genes that showed significant variation between CD45-/CD90+ cells isolated from normal, patient normal stroma and patient tumor stroma. Gene signatures from MSCs were subjected to hierarchal clustering analysis but could not define cancer subtypes, but could define MSCs from normal or adjacent to tumor tissue. D) Heatmap demonstrating trends in expression of genes in Laser Capture Microdissection (LCM) of stromal and tumor samples derived from FFPE tissue and processed by SMART 3SEQ. Gene signatures from samples subjected to hierarchal clustering analysis and distinct gene expression signatures relating to MSC genes could differentiate stroma versus tumor tissues.

PMC10027225

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Single cell analysis of patient-derived MSCs.A) CD90+ cells were isolated from normal donors or patients with invasive breast cancer and subjected to single cell analysis. Gene expression profiles from single cells were clustered using tSNE, and 7 distinct cell clusters were observed. B) Candidate gene expression profiles were used to functionally characterize MSCs into 3 main subclasses (osteogenic, chondrogenic or adipogenic). C) Comparison of cells derived from healthy donors or breast cancer patients demonstrated proportional changes in number of cells contributing to specific clusters. D) Ontology categories associated with single cell populations.

PMC10027225

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Pathway and ontology analyses reveal that patient-derived MSCs demonstrate unique properties.A) Dot plot of proportion of cells in the respective cell clusters (Other, Chondrogenic, Patient-specific) expressing each gene (dot size), and average expression (color scale). B) Ontology and GSEA enrichment plots demonstrating category association of gene signatures expressed by patient-specific MSCs. C) Gene expression pattern in enriched pathways. Squares show enriched DEGs in the corresponding terms (rows). Color indicates the expression value of the DEGs (average logFC).

PMC10027225

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MSC-related gene expression can be observed in whole tumor single cell RNAseq.UMAP visualization of 130,246 cells analyzed by scRNA-seq and integrated across 26 primary breast tumors (from Wu et al [34]). Clusters were annotated for their cell types as predicted using canonical markers for epithelial cells (EPCAM), proliferating cells (MKI67), T cells (CD3D), myeloid cells (CD68), B cells (MS4A1), plasmablasts (JCHAIN), endothelial cells (PECAM1) and mesenchymal cells (fibroblasts/perivascular-like cells; PDGFRB) and gene signature-based annotation. A) Non-tumor MSC, perivascular and endothelial cells cluster on left side of plot demonstrated the majority of THY1 (CD90), CXCL12 and ACTA2 expression in the whole tumor. B) UMAP visualization of reclustered mesenchymal cells, including CAFs (6,573 cells), PVL cells (5,423 cells), endothelial cells (7,899 cells), lymphatic endothelial cells (203 cells) and cycling PVL cells, demonstrating that the majority of CD90 (THY1) positive cells residing in the assigned MSC cluster. C) Feature plots of gene expression of COL1A1, COL8A1 in whole tumor UMAP demonstrating gene expression restricted to MSC-associated clusters, and D) MSC UMAP demonstrating COL10A1 gene expression restricted to MSC/CAFS.

PMC10027225

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Treatment of MSCs with TGFβ inhibitor affects interactions with cancer cells.A) Cell proliferation assay of patient-derived or donor-derived MSCs treated with TGFβ-R1 inhibitors or control (DMSO). Points represent means with SEM. Significance was calculated by two-way repeated measures ANOVA using Tukey post hoc test and highlighted where p <0.05 (* A83-01 vs DMSO, ** Patient vs Donor). B) Colony formation assay measuring the number of colonies (CFU-F) formed after 7 day pretreatment with A83-01 or DMSO. Points represent individual patients or donors. Significance is highlighted where p <0.05 (* A83-01 vs DMSO, ** Patient vs Donor). C) Co-cultures of patient-derived MSCs with the estrogen receptor positive MCF7 breast cancer cell line in cells pretreated with Control (DMSO, left) or TGFβ R1 inhibitor (A8301, right). Scale bars represent 200 μm. D) Heatmap demonstrating differential gene expression in patient-derived MSCs treated with DMSO or A83-01 and E) associated relative gene expression (qPCR) of cells treated with DMSO, A-83-01 or Galunisertib. Significance was calculated Student’s t-test and highlighted where p <0.05 (*) or p <0.01 (**). F) Heatmap demonstrating differential gene expression in MCF7 cells co-cultured with patient-derived MSCs treated with DMSO or A83-01 and 01 and G) associated relative gene expression (qPCR) of cells treated with DMSO, A-83-01 or Galunisertib. Significance was calculated Student’s t-test and highlighted where p <0.05 (*) or p <0.01 (**).

PMC10027225

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Native mass spectrometry of C145S SARS-CoV-2 Mpro.From left to right, peaks show monomers cleaved (blue semicircle) an uncleaved (red semicircle), dimers formed by cleaved (blue circles) or half-cleaved (blue-red circle) particles, trimers formed by two cleaved and one uncleaved particles (two thirds blue, one-third red circles) and tetramers formed by two cleaved and two uncleaved particles (two-quarters blue, two-quarters red). Minor peaks of other forms are described in supplementary materials. Graphs were plotted from individual native mass spectrometry experiments.

PMC10027274

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Cryo-EM data processing schematic for C145S SARS-CoV-2 Mpro.a Aligned micrographs, with scale bar at the bottom. b CTF-function calculated from obtained micrographs. c Extracted particles examples. d Detailed schematic of steps taken for final reconstruction, highlighting obtained 2D and 3D classes, and first high-resolution reconstruction. e Fourier shell correlation (FSC) between half maps of the final reconstructions. At the top, graph shows FSCs versus spatial frequency calculated in directions x (blue), y (green) and z (red). Average cos phase is in black, and global FSC is plotted in yellow. At the bottom, percentage of per angle FSC (blue) overlaid with gold standard FSC plot (red). f Local resolution projected on the final map from two orientations.

PMC10027274

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A. Overview of SARS-CoV-2 C145S Mpro cryo-EM model.a Four-sides rotation view of final map displayed as surface, with chains A and B coloured in white and grey, respectively, and active site peptide map coloured in cyan. b Chain A (blue) domain III model fitted into final map (grey). c Chain A (blue) and B (salmon) interface region fitted into final cryo-EM map (grey). d Superposition of X-ray Mpro model (yellow, PDB 7KPH), X-ray SARS-CoV-2 C145S Mpro (pink, PDB 7N5Z) and SARS-CoV-2 C145S Mpro cryo-EM model (dark blue). e SARS-CoV-2 C145S Mpro cryo-EM model chain A (left) and (right) coloured according its RMSD versus X-ray model of Mpro (PDB 7KPH).

PMC10027274

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Detailed view on Mpro C145S peptide interaction.a Active site view of Mpro C145S chain A surface (in grey) bound to nsp4-nsp5 peptide (yellow sticks). Subsites are denotated from S4 to S5’. b Detailed view of Mpro C145S chain A active site residues (in grey) bound to nsp4-nsp5 peptide (yellow sticks), with cryo-EM map showed as surface (contour level of 4.55). c Interaction scheme between nsp4-nsp5 peptide and Mpro C145S chain A. d Selected low-pass filtered particles, highlighting dimer particles (marked with a blue line) bound to monomeric uncleaved particles (marked with a red line). Scale bar is show at the bottom left. e Schematic representation of Mpro C145S dimer (blue) bound to uncleaved particles (red).

PMC10027274

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Schematic representation of in solution dynamics of SARS-CoV-2 C145S Mpro monomeric form (sample 1) analyzed with SEC-MALS.a Control reaction containing monomers at 0 h (top), after 24 h incubation (middle) and after 48 h (bottom). b Monomers conversion reaction in presence of non-covalent inhibitor MAT-POS-e194df51-1 at 0 h (top), after 24 h incubation (middle) and after 48 h (bottom). c Monomers conversion reaction in presence of covalent inhibitor Nirmatrelvir at 0 h (top), after 24 h incubation (middle) and after 48 h (bottom).

PMC10027274

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Schematic representation of in solution dynamics of SARS-CoV-2 C145S Mpro tetrameric form (sample 2) analyzed with SEC-MALS.a Control reaction containing tetramers at 0 h (top), after 24 h incubation (middle) and after 48 h (bottom). b Tetramers conversion reaction in presence of non-covalent inhibitor MAT-POS-e194df51-1 at 0 h (top), after 24 h incubation (middle) and after 48 h (bottom). c Tetramers conversion reaction in presence of covalent inhibitor Nirmatrelvir at 0 h (top), after 24 h incubation (middle) and after 48 h (bottom).

PMC10027274

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Cartoon model of X-ray structure of Mpro C145S bound to Nirmatrelvir, with chain A showed in yellow, and chain B showed in blue.Ser1 and Gln-1 alpha carbons are highlighted as red spheres. Native Mpro is shown as grey transparent cartoon, with Ser1 alpha-carbon highlighted as a green sphere.

PMC10027274

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Active site comparison between apo and intermediary states of Mpro.a Key active site residues (green sticks) of Mpro in apo form (top), cartoon view of active site in apo state in yellow (middle) and calculated electrostatic potential projected into surface of Mpro active site (bottom). b Key active site residues (green sticks) of Mpro C145S bound to intact peptide (top), cartoon view of active site from the respective form (middle) and calculated electrostatic potential projected of respective form (bottom). c Key active site residues (green sticks) of Mpro C145S covalently bound to cleaved peptide forming the enzyme-substrate intermediary complex (top), cartoon view of active site from the respective form (middle) and calculated electrostatic potential projected of respective form (bottom). d Key active site residues (green sticks) of Mpro C145S in complex with post-cleaved peptide (top), cartoon view of active site from the respective form (middle) and calculated electrostatic potential projected of respective form (bottom). The transparent sticks and cartoons (grey) in the top and middle figures represent the structural position from the relative elements of the previous step.

PMC10027274

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SBS signaturesin WM compared with MM.

PMC10027506

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Clonal and subclonal contribution of SBS signatures in WM. 96-class profile of genome-wide SBS mutations at the (A) clonal and (B) subclonal level. (C) SBS mutational signatures obtained after collapsing all genome-wide mutations at the clonal and subclonal level. (D-E) 96-class profile of SBS mutations specific to the immunoglobulin loci at the (D) clonal and (E) subclonal level. (F) SBS mutational signatures obtained after collapsing all mutations within immunoglobulin loci at the clonal and subclonal level.

PMC10027506

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Structural variants in WM. (A) Example of a chromoplexy event between chromosomes 1, 6, 10, and 12. (B-D) Examples of structural variants affecting driver genes: translocations affecting NFKB2 (B/C) and MEF2B (D). (E) Total number of structural variants by disease stage.

PMC10027506

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5ccab7ea19c64f6d9346846b4568c0d9

Copy number profiles from Waldenström's macroglobulinemia. Cumulative copy number profiles across samples with (A) IgM MGUS or symptomatic precursor WM, and (B) symptomatic and treatment-exposed Waldenström's macroglobulinemia. Samples from patients with asymptomatic disease that later progressed were considered together with samples from symptomatic patients. In (A/B), red, gain; blue, deletion. ∗ = peak is significantly different between group according to GISTIC analysis. (C) Heatmap of mutations according to clinical stage. (D) Heatmap of copy number and structural variants according to clinical stage.

PMC10027506

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Molecular timing analysis. Copy number profiles from; (A) MYD88-wt sample, demonstrating gains in chromosomes 3, 5, 12, 15, 16, (B) MYD88-wt sample with gain in chromosome 12, (C) MYD88-mutant sample with gain of 3q and (D) MYD88-mutant sample with gains of chromosomes 4 and 18. (E-H) Molecular timing analysis for the same 4 patient samples, using the ratio of duplicated:nonduplicated mutations within clonal chromosomal gains. Red, molecular time in chromosome 12 gains; aqua, gains in other chromosomes in patients harboring a chromosome 12 gain; black, other gains.

PMC10027506

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e2c34b07fcd445838676af48f61debb9

Pre-extracorporeal membrane oxygenation (ECMO) conventional protective ventilation compared to ultra-lung protective mechanical ventilation during ECMO. ACV assist-control ventilation, BIPAP-APRV bilevel positive airway pressure-airway pressure release ventilation, RR respiratory rate, PEEP positive end-expiratory pressure, PBW predicted body weight, Vt tidal volume, FiO2 inspired fraction in O2, Pplat plateau pressure, ∆P driving pressure, Phigh high pressure, Plow low pressure, Ti inspiratory time, Te expiratory time

PMC10027594

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Tools to set positive end-expiratory pressure on venovenous extracorporeal membrane oxygenation (VV-ECMO). RCT randomized controlled trial, CT computed tomography

PMC10027594

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Inner side patient's right thigh. a Wound upon arrival in the nutrition department: fibrinous edges and necrotic central zone. b Intermediate state after wound trimming, during VAC therapy: diameter of the wound was reduced and substance is regained. c After the skin graft: healthy edges and good epidermalization. VAC, vacuum-assisted closure system.

PMC10028363

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Integral carbon selectivity and methanol throughput values calculated until the moment when conversion of methanol drops below 75%. Reaction conditions: (a) 350 °C, 25 mg of catalyst, 0.75 kPa of MeOH, carrier −10 mL·min–1 He, WHSV 0.3 h–1; (b) 400 °C, 25 mg of catalyst, 6 kPa of MeOH, carrier −30 mL·min–1 He, WHSV 6 h–1; and (c) 450 °C, 25 mg of catalyst, 12.3 kPa of MeOH, carrier −30 mL·min–1 He, WHSV 12 h–1.

PMC10028611

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Total amounts of methanol converted normalized by number of BAS for respective catalysts.

PMC10028611

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Ion signal as a function of m/z and photon energy from the detected products and intermediates over HZSM-5 (a) and Ca/ZSM-5 (b) catalysts during the MTH reaction. Reaction conditions: 350 °C; 100 mg of the catalyst, 12.3 kPa of methanol, carrier −75 mL·min–1 He. The data acquisition took 8 h for each catalyst.

PMC10028611

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Comparison of recorded and literature photoelectron spectra42−48 for selected m/z = 30, 42, and 58 channels over HZSM-5 (left) and Ca/ZSM-5 (right), corresponding to various oxygenate and hydrocarbon species. Reaction conditions: 350 °C, 100 mg of the catalyst, 12.3 kPa of methanol, carrier −75 mL mL·min–1 He.

PMC10028611

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Step-response MTH experiments performed at 350 °C. (a) Total hydrocarbon traces of all catalysts compared to Ar tracer. (b) Amount of hydrocarbons eluted from zeolites after methanol was switched off. Conditions: 350 °C, 50 mg of catalyst, 18.3 min switch, 5 mL·min–1 He flow with 1.5 kPa of MeOH + 5 mL·min–1 side flow of Ar tracer.

PMC10028611

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Operando TGA profiled recorded during switching from methanol-containing He flow to dry He over HZSM-5, Ca/ZSM-5 and Na/ZSM-5 catalysts. (a) TGA profiles and amount of adsorbates retained and flushed during three methanol switches for ZSM-5 catalysts (inset). (b) MS profiles of m/z = 31 signal corresponding to methanol recorded simultaneously with TG profiles. Conditions: 350 °C, 10 mg of catalyst, carrier −80 mL·min–1 He, 0.75 kPa of MeOH.

PMC10028611

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1H–13C CP MAS NMR of the used catalysts from continuous flow experiments after 10 min (a) and 3 h (b) on stream. Conditions: 350 °C, 100 mg of the catalyst; carrier −30 mL·min–1 He, 12 kPa of 13C MeOH. Sidebands are denoted with asterisks.

PMC10028611

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1H–13C{1H} HETCOR MAS NMR 2D of the used catalysts from continuous flow experiments after 3 h of stream. Conditions: 350 °C, 100 mg of catalyst, carrier −30 mL–1·min He, 12 kPa of 13C MeOH.

PMC10028611

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Enlarged regions of Δ abs spectra: (a–c) OH-region and (d–f) region of methanol adsorption, and (g–i) 1750–1300 cm–1 region. Δ abs spectra were obtained by subtraction of the first spectrum recorded at 350 °C in absence of methanol from all other spectra. Conditions: 350 °C, 15 mg of catalyst pellet, carrier −130 mL·min–1 He, 0.12 kPa of MeOH.

PMC10028611

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Bands of interest integrated from Δ abs spectra from operando IR measurements for ZSM-5 catalysts in presence and absence of the methanol feed: (a) BAS, (b) EfAl and Ca-OH, (c) methoxy groups, and (d) polymethylated benzenes. Conditions: 350 °C, 15 mg of catalyst pellet, carrier −130 mL·min–1 He, 0.12 kPa of MeOH.

PMC10028611

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IR measurements of ZSM-5 catalysts combined with temperature-programmed experiments with water. Conditions: 150–500 °C, heating rate 5 °C·min–1, 15–20 mg of catalysts, carrier −130 mL·min–1 He, 0.07 kPa of water.

PMC10028611

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(a) Positions within the catalyst bed where the XRD data were acquired. (b–d) Unit cell volumes derived from Rietveld refinement of operando XRD data for HZSM-5, Ca/ZSM-5, and Na/ZSM-5 catalysts and after 5 h on stream and subsequent switch off the methanol for 30 min; MS spectra of the reaction are attached below. Conditions: 400 °C, 20 mg of catalyst, carrier −50 mL–1·min He, 13 kPa of MeOH.

PMC10028611

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Type of antimicrobial stewardship recommendation.

PMC10028943

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Intensive care unit stay in patients receiving elective coronary artery bypass grafting. Patients who had elective coronary artery bypass grafting are divided by temperature upon ICU admission. Their intensive care unit stays were plotted.

PMC10030842

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Literacy rate by province and gender in Pakistan. Source: Author construction based on data from PSLM Bureau of Statistics, Pakistan. Figure 2 displays the trend of per capita income from 2005 to 2019, one of the inevitable indicators of educational achievement. The statistics calculate a sharp drop in per capita income after 2010, which improved in 2012 but eventually declined after 2016

PMC10031191

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Household’s income in Pakistan. Source: Author construction based on data from PSLM Bureau of Statistics, Pakistan. Figure 2 displays the trend of per capita income from 2005 to 2019, one of the inevitable indicators of educational achievement. The statistics calculate a sharp drop in per capita income after 2010, which improved in 2012 but eventually declined after 2016

PMC10031191

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Education attainment by age (2005–2019). Source: Author construction based on data from PSLM Bureau of Statistics, Pakistan. Figure 3 expresses the predictive margins between the age of the persons living in the household and their education levels. The probability of primary education attainment decreases after 25 years of age, whereas it is the opposite for the tertiary level. Meanwhile, with the increase in age, it is more likely to achieve secondary education

PMC10031191

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Flowchart of the experimental design for RNA-seq and data analysis

PMC10031896

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Overview on the expression data. A Normalization boxplot representing sequencing depth and rescaled log2 counts per million for 16 time points (16*3 biological replicates). B Gene-wise variance estimation, mean vs. standard deviation plot for normalized row-wise gene counts. The horizontal red line is the median estimator. C Variance-stabilized transformation of normalized raw counts and Pearson correlated clustering of expression patterns for the 100 most-expressed genes

PMC10031896

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Clustered and scaled expression patterns for the top 500 differentially expressed (DE) genes. Each group represents a gene expression pattern shared among different DE genes

PMC10031896

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Putative regulatory motifs for clusters enriched in genes associated with pathogenicity, exocytosis and vesicle transport, ion channels and calcium binding proteins, plant cell wall degrading enzymes and transcription factors. The X-axis in the expression profile shows 16 time-points of Pl. halstedii lifecycle and on the Y-axis the gene expression scaled according to Z-score. The number shown above every graph gives the cluster number from the current study. The identified motifs are given below each of the expression clusters. Known motifs are shaded in pink, new motifs in turquoise

PMC10031896

12864_2023_9214_Fig4_HTML.jpg

e930c13e95644a91a5a517fb713a9748

Bending-induced 5-fold twin formation in a single-crystalline Au nanocrystal. (a) TEM image of a single-crystalline Au nanocrystal. (b–e) Successive emission of partial dislocations on four different twinning systems in the Au nanocrystal. The GB angle increases from 12 to 16° upon bending. (f) Transformation of SF bundles into the twin variants of the 3-fold twin. (g) TB migration mediated by partial dislocation slip. (h) Formation of a 4-fold twin. (i) Formation of a 5-fold twin through lattice reorientation. All of the scale bars are 2 nm.

PMC10032584

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44e93bcdc26942de9d5ac71eb4fd0f6f

MD simulation showing the atomic-scale process of 5-fold twin formation in a single-crystalline Au nanocrystal upon bending. (a) The bending Au nanocrystal before defect nucleation. (b) Successive partial dislocations emit from the free surface and terminate near the neutral plane, resulting in the formation of a TB and a GB. (c) Transformation of a distorted area into a twin via atom adjustment. (d) Formation of a 3-fold twin through partial dislocation slip-mediated lattice reorientation. (e) Formation of a Σ27 GB at the node of the 3-fold twin. (f) Formation of two TBs caused by the decomposition of Σ27 GB. Based on a common neighbor analysis,50 the atoms with face-centered cubic (FCC), hexagonal-close-packed (HCP), and other structures are colored in green, red, and gray, respectively.

PMC10032584

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fe50b919024a441ea118bb8c0c0c3e78

Shear- and tension-induced formation and dissolution of a 5-fold twin in a multifold twinned nanocrystal. (a) An as-fabricated Au nanocrystal with a 4-fold twin structure. The nanocrystal is viewed along [1̅10]. (b) Formation of a 5-fold twin via successive twinning partial slip along the preexisting SF and TBs. (c–g) Detwinning of a 5-fold twin upon reverse shear loading. A 2-fold twin and a Σ9 GB form after the detwinning process. (h–j) Formation of a 5-fold twin through partial dislocation slipping and Σ9 GB decomposition under tensile loading at a strain rate of 10–3 s–1. (k, l) Change in twin morphology of the 5-fold twin upon shear loading. All of the scale bars are 2 nm.

PMC10032584

nl2c03852_0003.jpg

e888b5ca7266422bb6cec5475ce75942

MD simulation showing atomic-scale processes of 5-fold twin formation in the Au nanocrystal and Σ9 GB decomposition. (a) A Au nanocrystal with a TB intersected with a Σ9 GB under ⟨112⟩ compression. (b) Formation of four TBs via Σ9 GB decomposition upon compression. (c–f) Adjustment of the FFT via a series of partial dislocation slip from the free surface and Σ9 GBs. (g–j) Atomic scale processes of the decomposition of Σ9 {111}/{115} (g, h) and Σ9 {001}/{112} (i ,j) asymmetrical tilt GBs. Based on a common neighbor analysis,50 the atoms with FCC, HCP, and other structures are colored in green, red, and gray, respectively.

PMC10032584

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4c3c5752760445d38fef26c274edd2e0

FFT formation in the neck area of a Au nanocrystal with a TB parallel to the tensile loading direction. (a, b) In situ atomic-scale observation of FFT formation in the neck of the Au nanocrystal loaded along ⟨112⟩ direction at room temperature under a strain rate of 10–3 s–1. The nanocrystal is viewed along [1̅10]. All of the scale bars are 2 nm. (c) MD snapshot showing dislocation activities on inclined {111} planes. Based on a common neighbor analysis,50 the atoms with an HCP structure are colored in red, and the atoms with other structures are colored in gray. (d) Formation of a neck in the bitwinned Au nanocrystal at the final stage of the tensile test. (e, f) Series of MD snapshots showing FFT formation in the neck area of a Au nanocrystal.

PMC10032584

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975fef6603484bd78544ff869729cad3

The molecular structure, in vitro pan-genotype and -serotype activity, and mechanism of action of JNJ-1802.a, The molecular structure of JNJ-1802. b, In vitro antiviral activity in Vero E6 cells against a panel of clinical isolates23. Data are mean EC50 values. The asterisk and hash symbols indicate that the DENV strain carries a T108I (*) or T108A (#) mutation in NS4B. Where indicated by a triangle, the mean EC50 in Vero E6 cells was calculated by setting the values below the 0.04 nM threshold at 0.04 nM. A, American; AA, Asian American; AI, Asian I; AII, Asian II; C, cosmopolitan; S, sylvatic. c, Schematic of the DENV NS4B membrane topology50,51. JNJ-1802-selected resistance mutations in orange were present in at least 99% of the quasispecies at the end point (passage 42 (sample A); passage 50 (sample B)). Mutations in black were present in less than 50% of the quasispecies at the end point. Mutations in blue appeared transiently and had disappeared at the end of the experiment. The diagram was created in part using the Servier Medical Art library (https://smart.servier.com/). d, JNJ-1802 prevents DENV NS3–NS4B interaction. Three independent co-immunoprecipitation experiments were performed to establish the JNJ-1802 dose–response curve for the NS3–NS4B interaction. Representative western blots are shown in Extended Data Fig. 2a,b. Signal intensity ratios were determined as described in the Methods. Data are mean ± s.e.m. For the comparison of NS3:NS4B–HA ratios between JNJ-1802 treated samples and DMSO control, P values were calculated using repeated-measures one-way analysis of variance (ANOVA) with subsequent Dunnett’s multiple-comparisons test; NS, not significant. EC50, 50% effective concentration; DMSO, dimethyl sulfoxide; IP, immunoprecipitation; TM, transmembrane.Source Data

PMC10033419

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bc4c3aed70674460897c4090ce77f79b

In vivo efficacy of JNJ-1802 (b.i.d.) against DENV-1–4 after infection in AG129 mice.a, Schematic of viraemia studies against DENV-2. b, The effect of JNJ-1802 on viraemia on day 3 after infection in DENV-2-infected mice treated b.i.d. with 60, 20, 6, 2, 0.6, 0.2 mg per kg per day JNJ-1802 (n = 7, 14, 14, 16, 16 and 13, respectively; without anti-flavivirus antibodies), compared with vehicle-treated mice (n = 24). Treatment started 1 h before infection. Undetermined Ct values imputed at a value of 40 (the limit of detection (LOD)) correspond to 2.6 log10 viral RNA copies per ml. Pooled data of three independent studies were analysed using two-way ANOVA with Dunnett’s multiple-comparison test. The LLOQ is 3.7 log10 viral RNA copies per ml. c, Schematic of the survival study. d, The effect of JNJ-1802 on survival in mice treated with anti-flavivirus antibodies (clone 4G2) receiving b.i.d. 20, 6, 2, 0.6 or 0 mg per kg per day JNJ-1802 starting 1 h before infection. Data are from a single study (n = 10 mice per group). Two-sided Fisher’s exact tests were used on day 25 with Bonferroni’s multiple-comparison test. e, Outline of the viraemia/survival studies against DENV-1, DENV-3 and DENV-4. f–k, The effect of JNJ-1802 on survival (n = 10 mice per group, except for DENV-3 vehicle, for which n = 11 mice per group) (f–h) and viraemia (n = 5 mice per group) on day 3 after infection (i–k) in mice challenged with DENV-1/West Pac (f,i), DENV-3/C0360/94 (g,j) or DENV-4/703/4 (h,k), treated b.i.d. with 60, 6 or 0 mg per kg per day JNJ-1802. Treatment started 1 h before infection. The LOD is 1.7 log10 viral RNA copies per ml. Two-sided Fisher’s exact tests were used on day 6 (survival) with Bonferroni’s multiple-comparison test. For viraemia, ordinary one-way ANOVA with Dunnett’s multiple-comparison test (DENV-1) and Kruskal–Wallis tests with Dunn’s multiple-comparison test (DENV-3 and DENV-4) were performed. P values are shown in the figures. HEP, human end point. For a, c and e, the schematics were adapted from ref. 3. The dagger symbol indicates the day of euthanasia.Source Data

PMC10033419

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35d67db3c7a0455093bab0e5ec251e2a

In vivo efficacy of JNJ-1802 against DENV-2 in NHPs by measuring viral RNA load, NS1 protein, IgM/IgG response and TCID50.a, Schematic of the viraemia studies using rhesus macaques. b, The effect of JNJ-1802 on viral RNA in plasma of rhesus macaques (R1–R12) treated q.d. with vehicle, or 0.01, 0.18 or 3 mg per kg per day JNJ-1802 (n = 3 per group). Treatment started 1 day before infection. Analyses were performed in triplicate. Data are mean ± s.d. The LLOQ or LOD of 1,286 GCE per ml is indicated by a dotted line in the graphs. Undetectable levels are shown as 100 GCE per ml. c, The levels of NS1 protein in serum samples of rhesus macaques. Analyses were performed in duplicate. Data are mean. An index value of less than 0.9 is considered to be negative, between 0.9 and 1.1 equivocal, and all values greater than 1.1 positive. The area between 0.9 and 1.1 is indicated by a grey horizontal bar. d,e, The levels of IgM (d) or IgG (e) antibodies in the sera of groups of rhesus macaques. IgM/IgG antibody levels are expressed as the mean index value from two independent assays. An index value of greater than 1.0 is presumptive for the presence of IgM/IgG antibodies to DENV. The cut-off value of 1.0 is indicated by a dotted line in the graphs. f, Quantification of infectious virus in plasma samples of rhesus macaques using the 50% tissue culture infective dose (TCID50) assay. Only samples that tested positive by RT–qPCR assay or in the NS1 ELISA, as well as samples with indeterminate outcomes in these assays, were analysed. NA, not applicable. For a, the schematic was adapted from ref. 3, Springer Nature Limited. The dagger symbol indicates the day of euthanasia.Source Data

PMC10033419

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83f1b4b0fdc2443cb097d41094a19a3c

The in vivo efficacy of JNJ-1802 against DENV-1/45AZ5 was examined in NHPs by measuring viral RNA load and IgM/IgG response.a, Schematic of the DENV-1/45AZ5 study. b, The effect of JNJ-1802 on viral RNA in rhesus macaques (R1–R12) infected with DENV-1/45AZ5 (0.5 ml at 1.2 × 105 PFU per ml) and treated with JNJ-1802 at 6 mg per kg per day once daily (n = 6; right) in comparison to the vehicle-treated group (n = 6; left). Treatment started 3 days before infection. RNA levels are expressed in GCE per ml. Data are mean ± s.d. The LLOQ of 100 GCE per ml is indicated by a dotted line in the graphs. c,d, ELISA data are presented as end-point titres by study day, which is defined as the reciprocal of the highest dilution of the serum that gives a positive signal. Samples were assayed in duplicate. Data are mean. For a, the schematic was adapted from ref. 3, Springer Nature Limited. The dagger symbol indicates the day of euthanasia.Source Data

PMC10033419

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ea9238576a5d4cce8f737de1ae500d0e

In vitro resistance selection profile of JNJ-1802 against DENV-2.a, b, The dynamics of emerging mutations were studied using whole virus genome sequencing in two independent experiments (Experiment A (a) and experiment B (b)). Each coloured line shows the kinetics of appearance of a particular mutation during virus passaging in the presence of JNJ-1802; each mutation is shown in the same colour over the different experiments. Emerging mutations were defined as amino acid changes compared to the start virus (DENV-2/RL), which were not present in the viruses that were passaged in parallel without any drug exposure. Whole genome sequencing was performed on DENV variants harvested at every 5th passage (P) and at the end of the experiments (i.e., P42 for experiment A and P50 for experiment B). One passage represents a one-week time span. The dotted line represents the cut off (15%) for the detection of variants compared with wild-type in the virus population. The increasing EC50 values, as determined by microscopic evaluation of virus-induced CPE, are depicted below the graphs. c, Level of compound resistance conferred by NS4B mutations in DENV-2/16681 induced by JNJ-1802. Fold change (mean ± standard deviation) in compound resistance is calculated as the EC50 of the compound against the mutant sub-genomic DENV-2/16681 reporter replicon divided by the EC50 of the compound against wild-type sub-genomic DENV-2/16681 reporter replicon. Data are from at least three independent experiments. d, Natural occurrence of the NS4B mutations in clinical isolates. *The natural occurrence of the mutations was retrieved from the Virus Pathogen Resource database (www.viprbrc.org; accessed in May 2020). Prevalence values of ≤0.1% are not shown. CPE, cytopathic effect; EC50, 50% effective concentration. Source Data

PMC10033419

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74004240f005448ba5996d3a3332720c

JNJ-1802 prevents DENV NS3-NS4B interaction.a, b, Huh-7 cells stably expressing T7 RNA polymerase and DENV-2 NS2B-NS3 were transfected with T7-based expression plasmids encoding NS4A-2K-NS4B(-HACt) (NS4B corresponding to wild-type [WT] or mutant NS4B). Four hours post-transfection, cells were treated with various concentrations of JNJ-1802 or DMSO, collected 14 h later, lysed and used for HA-specific pull-down and Western blot analysis of captured complexes. Representative Western Blot of the dose-response assays. Samples contain either WT NS4B or NS4B T108I (a) and mutant NS4B (V91A or L94F) (b). Please note the higher compound concentrations compared to (a). c–f, Western blot signal intensities of total lysates (input) obtained with an anti-HA-antibody were used to determine the dose-dependent effect of JNJ-1802 on the relative abundance of NS4B-containing species (mean ± standard error of the mean [SEM] of three independent experiments). Repeated measures one-way ANOVA and Dunnett’s multiple comparisons test were used to calculate P values. g, EC50 values (mean ± SEM) for the NS3-NS4B species ratio (a, b) and the change of 2K-NS4B proportion in total lysates (c–f) were obtained by fitting four-parameter dose-response curves to the results from each individual experiment. h, Experimental setup to investigate blockade of NS3-NS4B interaction with regard to the timing of JNJ-1802 addition. As indicated, cells were treated with 10 nM JNJ-1802 or DMSO, collected 8 h later, lysed and used for HA-specific pull-down and Western blot analysis. The diagram was created in part using the Servier Medical Art Library (https://smart.servier.com/). i, Representative Western blot from three independent experiments for the setup in (h). j–k, Effect of early and late treatment on the NS3/NS4B-HA species ratio in samples after HA-pulldown. Results are the mean and SEM from three independent experiments. Paired two-tailed t-test was applied to calculate P values. Uncropped images of a,b and i are presented in Supplementary Fig. 1–3. ns, not significant; Ct, C-terminal. Source Data

PMC10033419

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f3e2cf9a842d4ffd97d3ae6cbc41aced

In vivo efficacy of JNJ-1802 against DENV-2 infection, dosed once-daily for 3 days.a, Schematic outline of a viraemia study using AG129 mice adapted from Kaptein et al.3 b, Effect of JNJ-1802 on viraemia on Day 3 post-infection (p.i.) in mice orally treated once daily (q.d.) with a dose of 30, 3 or 0.3 (n = 8 for all groups) mg/kg/day JNJ-1802, compared to vehicle-treated mice (n = 8), with the first dose administered 1 h before infection. Data are from a single study. Undetermined cycle threshold values were imputed at a value of 40 (=limit of detection [LOD]), corresponding to 2.6 log10 viral RNA copies/mL. For statistical analysis, ordinary one-way ANOVA was used and Dunnett test to correct for multiple comparisons. p <0.0001 for 30 mg/kg/day versus vehicle; p <0.0001 for 3 mg/kg/day versus vehicle and p = 0.0983 not-significant (ns) for 0.3 mg/kg/day versus vehicle. LLOQ, lower limit of quantification, is 3.7 log10 viral RNA copies/mL. 4G2, anti-flavivirus antibody, clone 4G2. Source Data

PMC10033419

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a5775fb9f4e24e70854242cc1094a9ec

In vivo efficacy of JNJ-1802 against DENV-2 infection, dosed twice daily for 6 days.a, Schematic of the in vivo kinetics study. Compound administration started 1 h before infection and continued twice daily (b.i.d.) for 6 consecutive days. Each treatment group (n = 8) was equally divided into sub-groups A and B for blood collection on alternating days. b, Weight curves (mean values ± s.d.) of AG129 mice in the different treatment groups. c–e, Inhibitory effect of JNJ-1802 on viraemia in mice treated b.i.d. with 20, 2 or 0.2 mg/kg/day JNJ-1802 as compared to vehicle-treated mice. Data (mean ± s.d.) are from a single experiment. f, Schematic of the in vivo kinetics study in a therapeutic setting with treatment starting on Day 4 or 5 after DENV-2 challenge. In the control groups (vehicle and JNJ-1802) treatment started on the day of infection. Each treatment group (n = 10) was equally divided into sub-groups A and B for blood collection on alternating days. g, h, Inhibitory effect of JNJ-1802 on viraemia in AG129 mice with treatment (60 mg/kg/day, b.i.d. for 6 consecutive days) starting on Day 4 (g) and Day 5 (h) p.i. compared with the two control groups, vehicle and JNJ-1802. Data (mean ± s.d.) are from a single experiment. For both experiments (c–e; g, h), undetermined Ct values were imputed at a value of 40 (=limit of detection [LOD]), corresponding to 2.6 log10 viral RNA copies/mL (c-e) or 3.3 log10 viral RNA copies/mL (g-h). i, Mean AUC and 95% CIs were determined for each group depicted in (c–e; g, h). If CIs did not overlap, groups were considered to differ significantly. LLOQ, lower limit of quantification, is calculated to be 3.7 log10 viral RNA copies/mL (c-e) or 4.4 log10 viral RNA copies/mL (g-h). Schemes are adapted from Kaptein et al.3. Source Data

PMC10033419

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cd67ee3b2d7e473ab4dbfb55297c0b1b

Individual and mean JNJ-1802 plasma concentration-time profiles in non-human primates.a, Weight curves (mean values + standard deviation) of rhesus macaques in the different treatment groups (n = 3 per group, except for Day 3, n = 1 for 0.01 mg/kg/day and 0.18 mg/kg/day groups and n = 2 for 3 mg/kg/day group). b, Mean JNJ-1802 plasma concentration-time profile for the DENV-2 study in NHP. Rhesus macaques (n = 3 per group) were treated prophylactically with different doses (3, 0.18 or 0.01 mg/kg/day, once daily) of JNJ-1802, and subsequently experimentally infected with 102 TCID50 of DENV-2/16681. Dashed line indicates 3x protein-binding adjusted 90% effective concentration (pbaEC90) against DENV-2/16681 (8.2 ng/mL). c, Weight curves (mean values + standard deviation) of rhesus macaques in the different treatment groups (n = 6 per group). d, Mean JNJ-1802 plasma concentration-time profile for the DENV-1 study in NHP. Rhesus macaques were prophylactically treated with JNJ-1802 at 6 mg/kg/day once daily (n = 6, except for Day 1 n = 2) and subsequently infected with DENV 1/45AZ5 (0.5 mL at 1.2x105 plaque forming units [PFU]/mL). NHP, non-human primates. Source Data

PMC10033419

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c5e107ffbeae4a22a26c271730456369

Overall progression of individuals through study.

PMC10035812

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4c3c087575ef4e05af0b555c17a2c98b

The flow chart of patient selection and data analysis.

PMC10036588

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86e6dd105b7f42cd9c454a9b168683d6

Nomograms to predict 1-, 3-, and 5-year OS or CSS of NEPC patients. (A) Nomogram for OS; (B) Nomogram for CSS.

PMC10036588

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74abe22dd0204bb88463eb1133d91ff4

ROC curves to analyze the accuracy of the nomogram for 1-, 3-, and 5-year OS and CSS. ROC for OS at 1-year (A), 3-year (B), 5-year (C) in training group; ROC for OS at 1-year (D), 3-year (E), 5-year (F) in validation group; ROC for CSS at 1-year (G), 3-year (H), 5-year (I) in training group; ROC for CSS at 1-year (J), 3-year (K), 5-year (L) in validation group.

PMC10036588

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b9c72879ed284a619ace7ae9e39050d1

Calibration curves of the 1-, 3-, and 5-year OS of NEPC patients. 1-year (A), 3-year (C), 5-year (E) OS in training group; 1-year (B), 3-year (D), 5-year (F) OS in validation group.

PMC10036588

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503d1e471d5144f29319061c47c818f9

Calibration curves of the 1-, 3-, and 5-year CSS of NEPC patients. 1-year (A), 3-year (C), 5-year (E) CSS in training group; 1-year (B), 3-year (D), 5-year (F) CSS in validation group.

PMC10036588

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402d219cfe07484bb95825b66a6ce11a

DCA curves of the 1-, 3-, and 5-year OS of NEPC patients. 1-year (A), 3-year (B), 5-year (C) OS in training group; 1-year (D), 3-year (E), 5-year (F) OS in validation group.

PMC10036588

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13ea7f8133944fe886429917e5ff1a5c

DCA curves of the 1-, 3-, and 5-year CSS of NEPC patients. 1-year (A), 3-year (B), 5-year (C) CSS in training group; 1-year (D), 3-year (E), 5-year (F) CSS in validation group.

PMC10036588

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c9f7ef6b3ae042099e284e0c02829856

Kaplan–meier curves of OS and CSS of NEPC patients by different risk levels. OS in training set (A) and validation set (B); CSS in training set (C) and validation set (D).

PMC10036588

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d6e246d3e754443ba115fa681172308f

The rockburst in certain tunnel.

PMC10036632

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b1532884173145c2ab484520ea9c492a

Dynamic change diagram.

PMC10036632

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29fd2545b4b44b8ebe71fc38e3403573

Diagram of opposite fuzzy sets.

PMC10036632

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a6ee1bda7d5d49dcbb0afa33d34022fc

Diagram of relative difference function.

PMC10036632

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77d16b0b790a4ff49ec68f05a37742d5

The drawing of position relation.

PMC10036632

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4d7e081005e14c9cb01a50f89eabee91

Location of ventilation shafts of tunnel.

PMC10036632

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5f6bd9e812684dc8afc0b53f911528a3

Diagram of ventilation scheme of Zhongnanshan Highway Tunnel.

PMC10036632

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3adc9ace3e4945d79d52df29015bfd33

2 # shaft tower.

PMC10036632

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The risk evaluation process of rockburst intensity.

PMC10036632

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6e877d8bdb7c49e2a211cd433ffec4da

The effect of job stress on implementation quality was moderated by teachers’ perception of feasibility of PAX GBG + MTP. Teachers experiencing high levels of stress and felt the program was harder to use demonstrated greater (A) instructional support, and (B) classroom organization than those who were highly stressed and reported the program was easy to use.

PMC10036766

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a02d3e5c44e74fe497b1589490e81f07

Indications for thrombolysis. aSystolic blood pressure < 90 mm Hg or drop of > 40 mm Hg not explained by another cause. bHeart rate < 40 bpm

PMC10037295

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8a328c8ff50b4a35a9d245114b10e3bc

Thrombolysis contraindications according to societal guidelines. BP: Blood pressure; CPR: Cardiopulmonary resuscitation.

PMC10037295

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2f9553a90acc4b80abe0f87d19d86353

Diagnostic strategy in suspected cases of pulmonary embolism. PE: Pulmonary embolism; CTPA: Computed pulmonary tomography angiography.

PMC10037295

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e8e5fc7930b34056bc49d42a7d34b83e

Virtual Pharmacy Cardiac Optimization Clinic pathway.

PMC10037589

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b2ee9c41a6544533950326564a3c709a

Anticoagulation initiated following PCOC enrollment.

PMC10037589

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2a7ff02b0cdd480aa51bf7272cba8543

Recruitment and participation of the study.

PMC10038253

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eb3ce39e4d8f45a78f27be1eb696b844

Mediation model of the effects of demoralization on the relationship between fear and PTSD in both (A) high-risk group (N = 148) (Sobel’s test: Z = 3.64, p < 0.001) and (B) low risk group (N = 203) (Sobel’s test: Z = 3.72, p < 0.001). (FCV-19S = The Fear of COVID-19 Scale; DS-MV = Demoralization Scale—Mandarin Version; PCL-5 = Posttraumatic Stress Disorder Checklist for DSM-5; PM = the ratio of the indirect effect to the total effect).

PMC10038253

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7eb68b4c14c64c2d8bf26a3fcd5181d8

Mediation model of the effects of burnout and teamwork on the relationship between DASS and quality of life.(N = 351) (DASS = Depression, Anxiety, Stress Scale; CBI = Copenhagen Burnout Inventory; TPOT = Teamwork Performance Observation Tool; PM = the ratio of the indirect effect to the total effect).

PMC10038253

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b006f1d100c34d75bbc12329384c37b1

Map of Kenya and Uganda showing the location of buffalo sampling sites in Northern Uganda (Kidepo and Murchison Falls National Parks) and central Kenya (Ol Pejeta conservancy and the Maasai Mara game reserve)

PMC10039833

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fa175f24c0974a978a3b6d28d7666d5b

Box plot displaying the number of retained illumina reads after a stepwise filtering criterion. Central lines show the medians; box limits indicate the 25th and 75th percentiles as determined by R software; whiskers extend 1.5 times the interquartile range from the 25th and 75th percentiles; outliers are represented by dots; crosses represent sample means; bars indicate 95% confidence intervals of the means; data points are plotted as open circles. Thirty-seven Ugandan and 10 Kenyan buffalo samples were analysed

PMC10039833

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a0da73607cc2424e82e3d16473cad8df

Boxplot showing the distribution of the percent pairwise sequence identities when the antigen recognition sites of class I MHC alleles of the African buffalo are compared to alleles from different African cattle breeds and alleles from European Bos taurus

PMC10039833

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Amino acid alignment of buffalo class I MHC alleles. Plus sign ( +) marks sites under positive selection, codons which have ω > 1 with a significant Bayes Empirical Bayes probability are indicated by a single asterisk (*) if P > 95% or a double asterisk (**) if P > 99%. Codons known to be involved in antigen binding in cattle are marked with the letter P

PMC10039833

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Class I MHC distance tree depicting the relationship between predicted peptide-binding specificities of bovine alleles (black branch labels) and buffalo alleles (red branch labels). Alleles with similar peptide binding specificities cluster together and the closer class I MHC alleles branch, the larger the overlap between their predicted peptide-binding repertoires. For clarity, where buffalo alleles cluster so closely together such that the allele names overlap, only one has been retained

PMC10039833

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Heat-map visualization of the predicted peptide binding specificity overlaps between cattle and buffalo class I MHC transcripts inferred in MHCcluster. buffalo allele names are either prefixed ‘MF’, ‘KV’ or ‘OP’. All cattle alleles are prefixed ‘BoLA’. The colour key shows the MHC specificity distances between alleles. The bright orange represents the highest degree of overlap. Sequence logos describing predicted binding motif for the MHC molecule demonstrated overlap in key residues that underpin the binding specificity of bovine and buffalo class I MHC molecules. For clarity, where buffalo alleles cluster so closely together such that the allele names overlap, only one has been retained

PMC10039833

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Logos illustrating predicted peptide-binding motifs for buffalo (upper panel) and bovine (lower panel) class I MHC proteins. The height of each stack of symbols (y-axis) represents information content (the level of amino acid conservation) in each position, the relative frequency of a particular amino acid at that position is represented by the individual height of the amino acid symbol and under-represented amino acids at each position are shown on the negative section of the y-axis

PMC10039833

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The predicted amino acid sequences for the transmembrane (TM) and cytoplsmic domains of buffalo class I MHC. The transmembrane lengths and the cattle loci with matching transmembrane lengths are also shown. Also shown are alleles identified per animal. Where two alleles from the same animal are identical in this region, an asterisk is used to denotes that only one is shown in the figure. Recurrence of alleles between individuals is indicated by the + sign

PMC10039833

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Selection process of the study participants. KNHANES, Korea National Health and Nutrition Examination Survey.

PMC10040265

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