A two-way regularization method for MEG source reconstruction

The MEG inverse problem refers to the reconstruction of the neural activity of the brain from magnetoencephalography (MEG) measurements. We propose a two-way regularization (TWR) method to solve the MEG inverse problem under the assumptions that only a small number of locations in space are responsible for the measured signals (focality), and each source time course is smooth in time (smoothness). The focality and smoothness of the reconstructed signals are ensured respectively by imposing a sparsity-inducing penalty and a roughness penalty in the data fitting criterion. A two-stage algorithm is developed for fast computation, where a raw estimate of the source time course is obtained in the first stage and then refined in the second stage by the two-way regularization. The proposed method is shown to be effective on both synthetic and real-world examples.Comment: Published in at http://dx.doi.org/10.1214/11-AOAS531 the Annals of Applied Statistics (http://www.imstat.org/aoas/) by the Institute of Mathematical Statistics (http://www.imstat.org

Climate policy modeling: An online SCI-E and SSCI based literature review

This study utilizes the bibliometric method on climate policy modeling based on the online version of SCI-E from 1981 to 2013 and SSCI from 2002 to 2013, and summarizes several important research topics and methodologies in the field. Publications referring to climate policy modeling are assessed with respect to quantities, disciplines, most productive authors and institutes, and citations. Synthetic analysis of keyword frequency reveals six important research topics in climate policy modeling which are summarized and analyzed. The six topics include integrated assessment of climate policies, uncertainty in climate change, equity across time and space, endogeneity of technological change, greenhouse gases abatement mechanism, and enterprise risk in climate policy models. Additionally, twelve types of models employed in climate policy modeling are discussed. The most widely utilized climate policy models are optimization models, computable general equilibrium (CGE) models, and simulation models

Blocking interaction between SHP2 and PD‐1 denotes a novel opportunity for developing PD‐1 inhibitors

Small molecular PD‐1 inhibitors are lacking in current immuno‐oncology clinic. PD‐1/PD‐L1 antibody inhibitors currently approved for clinical usage block interaction between PD‐L1 and PD‐1 to enhance cytotoxicity of CD8+ cytotoxic T lymphocyte (CTL). Whether other steps along the PD‐1 signaling pathway can be targeted remains to be determined. Here, we report that methylene blue (MB), an FDA‐approved chemical for treating methemoglobinemia, potently inhibits PD‐1 signaling. MB enhances the cytotoxicity, activation, cell proliferation, and cytokine‐secreting activity of CTL inhibited by PD‐1. Mechanistically, MB blocks interaction between Y248‐phosphorylated immunoreceptor tyrosine‐based switch motif (ITSM) of human PD‐1 and SHP2. MB enables activated CTL to shrink PD‐L1 expressing tumor allografts and autochthonous lung cancers in a transgenic mouse model. MB also effectively counteracts the PD‐1 signaling on human T cells isolated from peripheral blood of healthy donors. Thus, we identify an FDA‐approved chemical capable of potently inhibiting the function of PD‐1. Equally important, our work sheds light on a novel strategy to develop inhibitors targeting PD‐1 signaling axis