Purpose: To conduct a phase I clinical trial with a second-generation oncolytic herpes simplex virus (HSV) expressing granulocyte macrophage colony-stimulating factor (Onco VEX GM-CSF
Kesterite Cu2ZnSnS4 is a promising photovoltaic material containing low‐cost, earth‐abundant, and stable semiconductor elements. However, the highest power conversion efficiency of thin‐film solar cells based on Cu2ZnSnS4 is only about 11% due to low open‐circuit voltage and fill factor mainly caused by antisite defects and unfavorable heterojunction interface. In this work, a postannealing procedure is proposed to complete a Cd‐alloyed Cu2ZnSnS4 device. The postannealing to complete the device significantly enhances the performance of the indium tin oxide and promotes the moderate interdiffusion of elements between the layers in the device. As a result of the diffusion of Cu, Zn, In, and Sn, the interfacial electron and hole densities are improved, leading to the achievement of a suitable band alignment for carrier transport. The postannealing also reduces the interface traps and deep‐level defects, contributing to decreased nonradiative recombination. Therefore, the open‐circuit voltage and fill factor are both improved, and an efficiency over 12% for pure sulfide‐based kesterite thin‐film solar cells is obtained.
Multiple myeloma cells secrete more disulfide bond-rich proteins than any other mammalian cell. Thus, inhibition of protein disulfide isomerases (PDI) required for protein folding in the endoplasmic reticulum (ER) should increase ER stress beyond repair in this incurable cancer. Here, we report the mechanistically unbiased discovery of a novel PDI-inhibiting compound with antimyeloma activity. We screened a 30,355 small-molecule library using a multilayered multiple myeloma cell-based cytotoxicity assay that modeled disease niche, normal liver, kidney, and bone marrow. CCF642, a bone marrowsparing compound, exhibited a submicromolar IC 50 in 10 of 10 multiple myeloma cell lines. An active biotinylated analog of CCF642 defined binding to the PDI isoenzymes A1, A3, and A4 in MM cells. In vitro, CCF642 inhibited PDI reductase activity about 100-fold more potently than the structurally distinct established inhibitors PACMA 31 and LOC14. Computational modeling suggested a novel covalent binding mode in activesite CGHCK motifs. Remarkably, without any further chemistry optimization, CCF642 displayed potent efficacy in an aggressive syngeneic mouse model of multiple myeloma and prolonged the lifespan of C57BL/KaLwRij mice engrafted with 5TGM1-luc myeloma, an effect comparable to the first-line multiple myeloma therapeutic bortezomib. Consistent with PDI inhibition, CCF642 caused acute ER stress in multiple myeloma cells accompanied by apoptosis-inducing calcium release. Overall, our results provide an illustration of the utility of simple in vivo simulations as part of a drug discovery effort, along with a sound preclinical rationale to develop a new small-molecule therapeutic to treat multiple myeloma.
A novel saturable absorber (SA) was fabricated by coating the topological insulator (TI) film on microfiber using pulsed laser deposition (PLD) method. The TISA device had an insertion loss of ~1.25 dB, a saturable intensity of 26.7 MW/cm2, a modulation depth of ~5.7%, and a nonsaturable loss of 20.5%. Upon employing this SA device, we established a passively mode-locked EDFL and achieved nearly free-chirped soliton pulse with 286 fs of pulse duration and >73 dB of signal to noise ratio (SNR). This result clearly evidences that the PLD is an effective scheme for practical SA device fabrication.
We fabricate and demonstrate strain-insensitive and high-temperature long-period gratings in endlessly single-mode photonic crystal fiber by use of focused pulses of a CO2 laser and a periodic stress relaxation technique without geometrical deformation and elongation of the fiber. The thermal dependence of mode coupling at 1299.59 nm is 10.9 pm/degrees C from 24 to 992 degrees C, whereas the coefficient of strain sensitivity is -0.192 pm/muepsilon up to the maximum strain of 2.74%epsilon. It is found for what is believed to be the first time that, in contrast with the traditional fiber case, the coupling resonance shifts toward shorter wavelengths under applied strain, indicating that the refractive index of the core is decreased as a result of the rebuilding of tension attributed to the stress-elastic effect, and the cladding modes is highly dispersive because of airholes arranged in the fiber cladding.
Sputtering followed by post annealing is extensively used for fabrication of copper indium gallium selenide (CIGS), copper zinc tin sulfide (CZTS) and copper zinc tin sulfur selenide (CZTSSe) thin film solar cells. In this work, Sb 2 Se 3 as an emerging alternative absorber was fabricated by an effective combination reaction of annealing sputtered Sb metallic precursors under Se vapor. Self-assembled growth of Sb 2 Se 3 thin films consist of large grains that across the whole films have been successfully fulfilled via this combination reaction.
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