Search

Image-based profiling has emerged as a powerful technology for various steps in basic biological and pharmaceutical discovery, but the community has lacked a large, public reference set of data from chemical and genetic perturbations. Here we present data generated by the Joint Undertaking for Morphological Profiling (JUMP)-Cell Painting Consortium, a collaboration between 10 pharmaceutical companies, six supporting technology companies, and two non-profit partners. When completed, the dataset will contain images and profiles from the Cell Painting assay for over 116,750 unique compounds, over-expression of 12,602 genes, and knockout of 7,975 genes using CRISPR-Cas9, all in human osteosarcoma cells (U2OS). The dataset is estimated to be 115 TB in size and capturing 1.6 billion cells and their single-cell profiles. File quality control and upload is underway and will be completed over the coming months at the Cell Painting Gallery:https://registry.opendata.aws/cellpainting-gallery. A portal to visualize a subset of the data is available athttps://phenaid.ardigen.com/jumpcpexplorer/.

Glucagon-like peptide 2 (GLP-2) is an intestinotropic peptide that binds to GLP-2 receptor (GLP- 2R), a class-B G protein-coupled receptor (GPCR) coupled with Gα(s). Few small-molecule agonists had been reported for class-B GPCRs, but we recently reported the first scaffold compounds of ago-allosteric modulators for human GLP-2R. Methyl 2-{[(2Z)-2-(2,5-dichlorothiophen- 3-yl)-2-(hydroxyimino)ethyl]sulfanyl}benzoate (compound 1) and its de-esterified derivative (compound 2) induced placental alkaline phosphatase (PLAP) activity in HEK293 cells overexpressing human GLP-2R and PLAP driven by cAMP response element. In this study, we observed that rat, Syrian hamster, and dog GLP-2Rs also responded to compounds 1 and 2 in the same reporter system. However, no agonistic activity of the compounds toward mouse GLP-2R was detected. Mutagenesis studies showed that mutant human GLP-2Rs with Pro392Leu substitution of mouse GLP-2R for human GLP-2R amino acid residues nullified the PLAP activity of compound 2, although these mutant receptors responded to GLP-2. This finding suggests that the Pro392 residue of human GLP-2R is essential for the agonistic activity of compound 2.

One of the extraordinary aspects of nonlinear wave evolution which has been observed as the spontaneous occurrence of astonishing and statistically extraordinary amplitude wave is called rogue wave. We show that the eigenvalues of the associated equation of nonlinear Schrodinger equation are almost constant in the vicinity of rogue wave and we validate that optical rogue waves are formed by the collision between quasi-solitons in anomalous dispersion fiber exhibiting weak third order dispersion.

Selected members of three classes of rhodacyanine dyes, [0,0]-, [1,0]-, and [0,0,0]-rhodacyanines, were synthesized and their in vitro antimalarial activities against Plasmodium falciparum K1 (chloroquine-resistant strain) as well as their in vivo activities against P. berghei in mice were determined. The novel [0,0,0]-rhodacynines, 3e and 3h, possessing a benzothiazole moiety, were shown to have highly promising antimalarial activities in vivo. Moreover, the [0,0,0]-rhodacyanines were found to be orally bioavailable.

The impact of third-order dispersion (TOD) on optical rogue wave phenomenon is investigated numerically. We validate the TOD coefficient by utilizing the eigenvalue of the associated equation of the nonlinear Schrodinger equation (NLSE).

Glucagon-like peptide 2 (GLP-2) is an intestinotropic peptide that binds to GLP-2 receptor (GLP-2R), a class-B G protein-coupled receptor. The GLP-2R antagonist GLP-2(3-33) has relatively high partial agonistic activity, and there are as yet no ideal known potent GLP-2R antagonists. We therefore prepared several truncated forms of human GLP-2 and characterized them by binding and reporter assays to find antagonists more potent than GLP-2(3-33). We found that GLP-2(11-33) was the most potent orthosteric GLP-2R antagonist, with binding activity almost equal to those of GLP-2 and GLP-2(3-33) and weaker intrinsic agonistic activity than GLP-2(3-33). GLP-2(11-33) retained weak agonistic activity toward human, cynomolgus monkey, dog, and Syrian hamster GLP-2Rs. However, it had no agonistic activity toward rat GLP-2R. GLP-2(11-33) potentiated the agonistic activity of an ago-allosteric modulator of GLP-2R, compound 1 (N-[1-(2,5-dichlorothiophen-3-yl)-2-(phenylsulfanyl)ethylidene]hydroxylamine), synergistically toward human GLP-2R. In the case of rat GLP-2R, GLP-2(11-33) decreased the agonistic activity of compound 1, although GLP-2 and GLP-2(3-33) increased this activity additively. These findings suggest that the binding sites of the ago-allosteric modulator and GLP-2 overlap, at least in rat GLP-2R. GLP-2(11-33) is a novel, useful tool for analyzing the mode of action of agonists and ago-allosteric modulators of GLP-2R.

We have demonstrated mode division multiplexed transmission using a space-optics based mode multiplexer/demultiplexer. In the experiment, 10 Gb/s NRZ-OOK signal and interfering CW light were simultaneously transmitted through a 2 km-long two-mode fiber with BER

We experimentally investigate the dispersion tolerance of transmitted OOK signals for all-optical NRZ-OOK to RZ-QPSK modulation format conversion using cross-phase modulation in nonlinear fiber at 10 Gsymbol/s by evaluating the bit error rate performance of the converted signal.

The ideal information carrier is invariable quantity during propagation in nonlinear dispersive fiber. This is eigenvalues of the associated equation of the nonlinear Schrodinger equation. We show the eigenvalue demodulation based on digital coherent technology.

We describe a design method of all-optical NRZ-OOK/RZ-QPSK modulation format converter by use of cross phase modulation in optical fiber. We experimentally show the validity of the design method.

Glucagon-like peptide 2 (GLP-2) is an intestinotropic peptide that binds to GLP-2 receptor (GLP-2R), a class-B G protein-coupled receptor (GPCR). Few synthetic agonists have been reported so far for class-B GPCRs. Here, we report the first scaffold compounds of ago-allosteric modulators for human GLP-2R, derived from methyl 2-{[(2Z)-2-(2,5-dichlorothiophen-3-yl)-2-(hydroxyimino)ethyl]sulfanyl}benzoate (compound 1).

We have investigated the pharmacology of sodium (R)-2-[4-(2,2-dimethyl-1,3-dioxan-5-yl) methoxy-3,5-dimethylpyridin-2-yl]methylsulfinyl-1H-benzimidazol (E3710), a new proton pump inhibitor (PPI), and its effect on gastric acid secretion. E3710 irreversibly inhibited H(+),K(+)-ATPase activity in pig gastric vesicles with an acidic internal environment with an IC(50) of 0.28 microM. Administration of E3710 (0.1, 0.2, 0.4, and 0.8 mg/kg; n = 6) intraduodenally in a gastric fistula model in dogs inhibited histamine-stimulated gastric acid secretion at 0 to 2 and 24 to 26 h after administration with ED(50) values of 0.18 and 0.22 mg/kg, respectively. The inhibition by E3710 was 2.3 times more potent than that of another representative PPI, esomeprazole (0.2, 0.4, 0.8, and 1.6 mg/kg; n = 6) at 0 to 2 h after administration (ED(50) = 0.40 mg/kg) and 2.8 times more potent at 24 to 26 h (ED(50) = 0.71 mg/kg). In the gastric fistula dogs, the intragastric pH wasor=4 for 17% (n = 27) of a 24-h period with vehicle alone, but when E3710 was administered, at 0.2 (n = 4), 0.4 (n = 8), and 0.8 mg/kg (n = 5), the pH wasor=4 for 40, 79, and 88% of a day, respectively. The corresponding values for esomeprazole at 0.8 (n = 4) and 1.6 mg/kg (n = 8) were 55 and 59%, respectively. In a crossover study with vehicle, E3710 at 0.4 mg/kg and esomeprazole at 1.6 mg/kg (n = 6), E3710 increased the intragastric pH to4 for 82% of a day compared with 61% of a day with esomeprazole. These results show that E3710 is a long-acting inhibitor of gastric acid secretion and a promising novel therapy for acid-related diseases, such as gastroesophageal reflux disease.

Fluorescent rhodacyanines, which display antimalarial activity in vitro and in vivo, stain plasmodial parasites at the erythrocytic stage. A good correlation between the antimalarial activity and the accumulation of the dyes is observed. A fused-rhodacyanine, which displays a strong fluorescent property itself, was designed as a new probe for plasmodial parasites. It appears to be specifically localized in the parasitic mitochondria.

Rhodacyanine dyes, potent antimalarial agents, was found to possess strong antileishmanial activity against Leishmania major in vitro. The efficacies of several compounds are comparable to one of clinically used amphotericin B.