An open science resource for establishing reliability and reproducibility in functional connectomics

Efforts to identify meaningful functional imaging-based biomarkers are limited by the ability to reliably characterize inter-individual differences in human brain function. Although a growing number of connectomics-based measures are reported to have moderate to high test-retest reliability, the variability in data acquisition, experimental designs, and analytic methods precludes the ability to generalize results. The Consortium for Reliability and Reproducibility (CoRR) is working to address this challenge and establish test-retest reliability as a minimum standard for methods development in functional connectomics. Specifically, CoRR has aggregated 1,629 typical individuals’ resting state fMRI (rfMRI) data (5,093 rfMRI scans) from 18 international sites, and is openly sharing them via the International Data-sharing Neuroimaging Initiative (INDI). To allow researchers to generate various estimates of reliability and reproducibility, a variety of data acquisition procedures and experimental designs are included. Similarly, to enable users to assess the impact of commonly encountered artifacts (for example, motion) on characterizations of inter-individual variation, datasets of varying quality are included

Integration of Different “-omics” Technologies Identifies Inhibition of the IGF1R-Akt-mTOR Signaling Cascade Involved in the Cytotoxic Effect of Shikonin against Leukemia Cells

Hematological malignancies frequently have a poor prognosis and often remain incurable. Drug resistance, severe side effects, and relapse are major problems of currently used drugs, and new candidate compounds are required for improvement of therapy success. The naphthoquinone shikonin derived from the Chinese medicinal herb, Lithospermum erythrorhizon, is a promising candidate for the next generation of chemotherapy. The basal cellular mechanism of shikonin is the direct targeting of mitochondria. Cytotoxicity screenings showed that the compound is particularly effective against leukemia cells suggesting an additional cellular mechanism. mRNA and miRNA microarrays were used to analyze changes in gene expression in leukemia cells after shikonin treatment and combined with stable-isotope dimethyl labeling for quantitative proteomics. The integration of bioinformatics and the three “-omics” assays showed that the PI3K-Akt-mTOR pathway was affected by shikonin. Deregulations of this pathway are frequently associated with cancerogenesis, especially in a wide range of hematological malignancies. The effect on the PI3K-Akt-mTOR axis was validated by demonstrating a decreased phosphorylation of Akt and a direct inhibition of the IGF1R kinase activity after shikonin treatment. Our results indicate that inhibiting the IGF1R-Akt-mTOR signaling cascade is a new cellular mechanism of shikonin strengthening its potential for the treatment of hematological malignancies

A Finite Volume Based Fully Nonlinear Potential Flow Model for Water Wave Problems

A new Fully Nonlinear Potential Flow (FNPF) numerical model has been developed for the simulation of nonlinear water wave problems. At each time step, the mixed boundary value problem for the flow field is spatially discretised by Finite Volume Method (FVM) and the kinematic and dynamic free surface boundary conditions are defined in a semi-Eulerian-Lagrangian form, which are used to update the wave elevation and velocity potential on the free surface. In the numerical model, waves are generated through a relaxation zone and absorbed by an artificial damping zone at the inlet and outlet of the numerical wave tank (NWT), respectively. Instead of a five-point smoothing technique, a more versatile fourth-order technique is developed to eliminate the possible saw-tooth instability at the free surface. Test cases with increasing complexities, such as wave generation and absorption, 2- and 3-Dimensional wave shoaling, and wave-cylinder interaction are simulated to assess its accuracy, convergence, and robustness. For all the cases considered, satisfactory agreements of free surface elevation and wave-induced forces against the experimental measurements and other existing numerical results are achieved. The developed numerical model fully utilises the existing functionalities in OpenFOAM and has the potential to provide an effective alternative to other FNPF based models for constructing a hybrid numerical wave tank model through its coupling with the multiphase flow models in OpenFOAM