In Situ SiRNA Assembly in Living Cells for Gene Therapy with MicroRNA Triggered Cascade Reactions Templated by Nucleic Acids

The in situ generation of siRNAs in living cells can greatly enhance the specificity and efficiency of gene therapy. Inspired by the natural molecular machines that organize different compartments sequentially in a limited space to facilitate cellular process, this work constructs a DNA nanomachine (DNM) by alternately hybridizing two pairs of DNA/RNA hybrids to a DNA scaffold generated by rolling circle amplification for highly efficient in situ siRNA assembly in living cells. After target cell-specific delivery of DNM, intracellular specific microRNA can work as a trigger to operate the DNM by initiating DNA cascade displacement reaction between DNA/RNA hybrids along the scaffold for continuous generation of siRNAs. Using miR-21 as a model, efficient siRNAs generation is achieved via DNA templated cascade reaction, which demonstrated impressive suppressions to VEGF mRNA and protein expressions in cells and in vivo tumor growth and indicated promising application of the designed strategy in gene therapy

Cost of preventing workplace heat-related illness through worker breaks and the benefit of climate-change mitigation

The exposure of workers to hot environments is expected to increase as a result of climate change. In order to prevent heat-related illness, it is recommended that workers take breaks during working hours. However, this would lead to reductions in worktime and labor productivity. In this study, we estimate the economic cost of heat-related illness prevention through worker breaks associated with climate change under a wide range of climatic and socioeconomic conditions. We calculate the worktime reduction based on the recommendation of work/rest ratio and the estimated future wet bulb glove temperature, which is an index of heat stresses. Corresponding GDP losses (cost of heat-related illness prevention through worker breaks) are estimated using a computable general equilibrium model throughout this century. Under the highest emission scenario, GDP losses in 2100 will range from 2.6 to 4.0% compared to the current climate conditions. On the other hand, GDP losses will be less than 0.5% if the 2.0 °C goal is achieved. The benefit of climate-change mitigation for avoiding worktime loss is comparable to the cost of mitigation (cost of the greenhouse gas emission reduction) under the 2.0 °C goal. The relationship between the cost of heat-related illness prevention through worker breaks and global average temperature rise is approximately linear, and the difference in economic loss between the 1.5 °C goal and the 2.0 °C goal is expected to be approximately 0.3% of global GDP in 2100. Although climate mitigation and socioeconomic development can limit the vulnerable regions and sectors, particularly in developing countries, outdoor work is still expected to be affected. The effectiveness of some adaptation measures such as additional installation of air conditioning devices or shifting the time of day for working are also suggested. In order to reduce the economic impacts, adaptation measures should also be implemented as well as pursing ambitious climate change mitigation targets

Stabilization of a Fabry-Perot interferometer using a suspension-point interferometer

A suspension-point interferometer (SPI) is an auxiliary interferometer for active vibration isolation, implemented at the suspension points of the mirrors of an interferometric gravitational wave detector. We constructed a prototype Fabry-Perot interferometer equipped with an SPI and observed vibration isolation in both the spectrum and transfer function. The noise spectrum of the main interferometer was reduced by 40 dB below 1 Hz. Transfer function measurements showed that the SPI also produced good vibration suppression above 1 Hz. These results indicate that SPI can improve both the sensitivity and the stability of the interferometer.Comment: 14 pages, 8 figures; added discussion; to be published in Physics Letters

EM Decay of X(3872) as the 11D2(2−+)1{^1D_2}(2^{-+}) charmonium

The recently BaBar results raise the possibility that X(3872) has negative parity. This makes people reconsider assigning X(3872) to the $1{^1D_2}(c\bar c)$ state. In this paper we give a general form of the wave function of $2^{-+}$ mesons. By solving the instantaneous Bethe-Salpeter equation, we get the mass spectrum and corresponding wave functions. We calculate electromagnetic decay widths of the first $2^{-+}$ state which we assume to be the X(3872) particle. The results are $\Gamma(2^{-+}(3872)\rightarrow J/\psi\gamma) = 1.59^{+0.53}_{-0.42}$ keV, $\Gamma(2^{-+}(3872)\rightarrow \psi(2S)\gamma) = 2.87^{+1.46}_{-0.97}$ eV and $\Gamma(2^{-+}(3872)\rightarrow \psi(3770)\gamma) = 0.135^{+0.066}_{-0.047}$ keV. The ratio of branch fractions of the second and first channel is about 0.002, which is inconsistent with the experimental value $3.4\pm 1.4$. So X(3872) is unlikely to be a $2^{-+}$ charmonium state. In addition, we obtain a relatively large decay width for $2^{-+}(3872)\rightarrow h_c\gamma$ channel which is $392^{+62}_{-111}$ keV.Comment: Revised versio

The Snakeskin-Mesh Complex of Smooth Septate Junction Restricts Yorkie to Regulate Intestinal Homeostasis in Drosophila

Tight junctions in mammals and septate junctions in insects are essential for epithelial integrity. We show here that, in the Drosophila intestine, smooth septate junction proteins provide barrier and signaling functions. During an RNAi screen for genes that regulate adult midgut tissue growth, we found that loss of two smooth septate junction components, Snakeskin and Mesh, caused a hyperproliferation phenotype. By examining epitope-tagged endogenous Snakeskin and Mesh, we demonstrate that the two proteins are present in the cytoplasm of differentiating enteroblasts and in cytoplasm and septate junctions of mature enterocytes. In both enteroblasts and enterocytes, loss of Snakeskin and Mesh causes Yorkie-dependent expression of the JAK-STAT pathway ligand Upd3, which in turn promotes proliferation of intestinal stem cells. Snakeskin and Mesh form a complex with each other, with other septate junction proteins and with Yorkie. Therefore, the Snakeskin-Mesh complex has both barrier and signaling function to maintain stem cell-mediated tissue homeostasis

Production and optical properties of liquid scintillator for the JSNS2^{2} experiment

The JSNS$^{2}$ (J-PARC Sterile Neutrino Search at J-PARC Spallation Neutron Source) experiment will search for neutrino oscillations over a 24 m short baseline at J-PARC. The JSNS$^{2}$ inner detector will be filled with 17 tons of gadolinium-loaded liquid scintillator (LS) with an additional 31 tons of unloaded LS in the intermediate $\gamma$-catcher and outer veto volumes. JSNS$^{2}$ has chosen Linear Alkyl Benzene (LAB) as an organic solvent because of its chemical properties. The unloaded LS was produced at a refurbished facility, originally used for scintillator production by the RENO experiment. JSNS$^{2}$ plans to use ISO tanks for the storage and transportation of the LS. In this paper, we describe the LS production, and present measurements of its optical properties and long term stability. Our measurements show that storing the LS in ISO tanks does not result in degradation of its optical properties.Comment: 7 pages, 4 figures

Calorimetric Evidence for Nodes in the Overdoped Ba(Fe0.9_{0.9}Co0.1_{0.1})2_{2}As2_{2}

We present low-temperature specific heat of the electron-doped Ba(Fe$_{0.9}$Co$_{0.1}$)$_{2}$As$_{2}$, which does not show any indication of an upturn down to 400 mK, the lowest measuring temperature. The lack of a Schottky-like feature at low temperatures or in magnetic fields up to 9 Tesla enables us to identify enhanced low-temperature quasiparticle excitations and to study anisotropy in the linear term of the specific heat. Our results can not be explained by a single or multiple isotropic superconducting gap, but are consistent with multi-gap superconductivity with nodes on at least one Fermi surface sheet.Comment: 5 pages 4 figure