Recent progress in mitochondria-targeted drug and drug-free agents for cancer therapy

The mitochondrion is a dynamic eukaryotic organelle that controls lethal and vital functions of the cell. Being a critical center of metabolic activities and involved in many diseases, mitochondria have been attracting attention as a potential target for therapeutics, especially for cancer treatment. Structural and functional differences between healthy and cancerous mitochondria, such as membrane potential, respiratory rate, energy production pathway, and gene mutations, could be employed for the design of selective targeting systems for cancer mitochondria. A number of mitochondria-targeting compounds, including mitochondria-directed conventional drugs, mitochondrial proteins/metabolism-inhibiting agents, and mitochondria-targeted photosensitizers, have been discussed. Recently, certain drug-free approaches have been introduced as an alternative to induce selective cancer mitochondria dysfunction, such as intramitochondrial aggregation, self-assembly, and biomineralization. In this review, we discuss the recent progress in mitochondria-targeted cancer therapy from the conventional approach of drug/cytotoxic agent conjugates to advanced drug-free approaches

Characterization of human papillomavirus type 16 pseudovirus containing histones

Lymphoproliferative responses following four immunizations with HPV16 PsVs from fraction I, II, or III. The mice were immunized four times with 50 ng of PsVs per dose at 2-week intervals. Mouse splenocytes were obtained 5 days after the fourth immunization. Mouse splenocytes were labeled with carboxyfluorescein succinimidyl ester (CFSE), stimulated with purified HPV16 L1 VLPs, and cultured for 4 days. The splenocytes were stained with allophycocyanin (APC)-conjugated anti-CD4 antibody (eBioscience, USA) and examined with a FACSCalibur flow cytometer (BD Bioscience, USA). To count CD4+ cells, the cells were gated according to forward and side scatter, and the upper-left segment of each graph was counted on FITC and APC scatter plots. Panel A shows the flow cytometry results for three individual mice. The value in panel B represents the mean ± SEM (n = 3). (DOCX 171 kb

Non-Einstein Viscosity Phenomenon of Acrylonitrile–Butadiene–Styrene Composites Containing Lignin–Polycaprolactone Particulates Highly Dispersed by High-Shear Stress

Lignin powder was modified via ring-opening polymerization of caprolactone to form a lignin–polycaprolactone (LPCL) particulate. The LPCL particulates were mixed with an acrylonitrile–butadiene–styrene (ABS) matrix at an extremely high rotational speed of up to 3000 rpm, which was achieved by a closed-loop screw mixer and in-line melt extruder. Using this high-shear extruding mixer, the LPCL particulate size was controlled in the range of 3395 nm (conventional twin-screw extrusion) down to 638 nm (high-shear mixer of 3000 rpm) by altering the mixing speed and time. The resulting LPCL/ABS composites clearly showed non-Einstein viscosity phenomena, exhibiting reduced viscosity (2130 Pa·s) compared to the general extruded composite one (4270 Pa·s) at 1 s–1 and 210 °C. This is due to the conformational rearrangement and the increased free volume of ABS molecular chains in the vicinity of LPCL particulates. This was supported by the decreased glass transition temperature (Tg, 83.7 °C) of the LPCL/ABS composite specimens, for example, giving a 21.8% decrement compared to that (107 °C) of the neat ABS by the incorporation of 10 wt % LPCL particulates in ABS. The LPCL particulate morphology, damping characteristics, and light transmittance of the developed composites were thoroughly investigated at various levels of applied shear rates and mixing conditions. The non-Einstein rheological phenomena stemming from the incorporation of LPCL particulates suggest an interesting plasticization methodology: to improve the processability of high-loading filler/polymer composites and ultra-high molecular weight polymers that are difficult to process because of their high viscosity

Typhoon‐induced, highly nonlinear internal solitary waves off the east coast of Korea

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/94585/1/grl22467.pd

Quantitative Analysis of Lens Nuclear Density Using Optical Coherence Tomography (OCT) with a Liquid Optics Interface: Correlation between OCT Images and LOCS III Grading

Purpose. To quantify whole lens and nuclear lens densities using anterior-segment optical coherence tomography (OCT) with a liquid optics interface and evaluate their correlation with Lens Opacities Classification System III (LOCS III) lens grading and corrected distance visual acuity (BCVA). Methods. OCT images of the whole lens and lens nucleus of eyes with age-related nuclear cataract were analyzed using ImageJ software. The lens grade and nuclear density were represented in pixel intensity units (PIU) and correlations between PIU, BCVA, and LOCS III were assessed. Results. Forty-seven eyes were analyzed. The mean whole lens and lens nuclear densities were 26.99 ± 5.23 and 19.43 ± 6.15 PIU, respectively. A positive linear correlation was observed between lens opacities (R2 = 0.187, p<0.01) and nuclear density (R2 = 0.316, p<0.01) obtained from OCT images and LOCS III. Preoperative BCVA and LOCS III were also positively correlated (R2 = 0.454, p<0.01). Conclusions. Whole lens and lens nuclear densities obtained from OCT correlated with LOCS III. Nuclear density showed a higher positive correlation with LOCS III than whole lens density. OCT with a liquid optics interface is a potential quantitative method for lens grading and can aid in monitoring and managing age-related cataracts

A Study on Virtual Reality Storytelling by Story Authoring Tool Algorithm

The objective of this study was to examine the storytelling principles of virtual reality contents, which are recently grabbing much attention, and the patterns of their generation rules and, based on the results, to analyze the elements and structure of a storytelling method suitable for virtual reality contents. In virtual reality environment, a story is usually being generated between choices made by a user who behaves autonomously under simulated environmental factors and the environmental constraints. This corresponds to a mutually complementary role of representation and simulation, which has been hotly discussed in the field of interactive storytelling. This study was conducted based on the assumption that such a mutually complementary realization is ideal for virtual reality storytelling. A simulation-based story authoring tool is a good example that shows this mutual complementation, in that it develops a story through various algorithms which involves the interaction of agents which occur within the strata of a virtual environment. Therefore, it can be a methodology for virtual reality storytelling. The structures and elements of narratives used in virtual reality storytelling which achieve balance of representation and simulation are much similar to an algorithm strategy of a simulation-based story authoring tool. The virtual reality contents released up to now can be classified into four categories based on the two axes of representation and simulation. The study focused on contents which are layered in higher strata of both representation and simulation. In the perspective of representation strata, these contents are actively using such elements as goal, event, action, perception, internal element, outcome, and setting element, which are constituents of ‘Fabula model’, to generate time relations and cause-effect relations. And in the perspective of simulation strata, the use of the ‘Late commitment’ strategy allowed users to understand the meanings of their actions taken during the process of experimenting with various dynamic principles within the environment