Installation of many distributed generations (DGs) could be detrimental to the power quality of utility grids. Microgrids facilitate effortless installation of DGs in conventional power systems. In ...recent years, dc microgrids have gained popularity because dc output sources such as photovoltaic systems, fuel cells, and batteries can be interconnected without ac/dc conversion, which contributes to total system efficiency. Moreover, high-quality power can be supplied continuously when voltage sags or blackouts occur in utility grids. We had already proposed a "low-voltage bipolar-type dc microgrid" and described its configuration, operation, and control scheme, through experiments. In the experiments, we used one energy storage unit with a dc/dc converter to maintain the dc-bus voltage under intentional islanding operation. However, dc microgrids should have two or more energy storage units for system redundancy. Therefore, we modified the system by adding another energy storage unit to our experimental system. Several kinds of droop controls have been proposed for parallel operations, some of which were applied for ac or dc microgrids. If a gain-scheduling control scheme is adopted to share the storage unit outputs, the storage energy would become unbalanced. This paper therefore presents a new voltage control that combines fuzzy control with gain-scheduling techniques to accomplish both power sharing and energy management. The experimental results show that the dc distribution voltages were within 340 V ± 5%, and the ratios of the stored energy were approximately equal, which implies that dc voltage regulation and stored energy balancing control can be realized simultaneously.
Current therapeutic strategies against glioblastoma multiforme (GBM) are futile mainly because of the poor access of drugs into malignant tissues, which is hindered by the tight blood-brain tumor ...barrier in the GBM vasculature. Nanomedicines have shown potential for circumventing the vascular barriers of GBM, particularly by targeting markers on the luminal side of endothelial cells in the blood vessels of GBM for achieving effective and selective translocation into the tumor. Thus, as the αvβ3 and αvβ5 integrins overexpressed on the endothelial cells of GBM can be targeted by cyclic-Arg-Gly-Asp (cRGD) peptide, herein, we developed cRGD-installed micellar nanomedicines loading epirubicin, the potent antiglioblastoma agent, through a pH-sensitive hydrazone-bond for effective treatment of GBM. These cRGD-installed epirubicin-loaded polymeric micelles (cRGD-Epi/m) achieved faster and higher penetration into U87MG cell-derived 3D-spheroids than the micelles without cRGD, conceivably through a cRGD-integrin mediated pathway. In vivo, the cRGD-installed micelles effectively suppressed the growth of an orthotopic GBM model by delivering high levels of epirubicin throughout the tumor tissue. These results indicate significant prospects for cRGD-Epi/m as an effective and translationable treatment against GBM.
cRGD-installed, epirubicin conjugated (via pH sensitive bond) polymeric micelles effectively suppressed the growth of an orthotopic GBM model by delivering high levels of epirubicin throughout the tumor tissue. Display omitted
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Magnetic refrigeration (MR) is a key technique for hydrogen liquefaction. Although the MR has ideally higher performance than the conventional gas compression technique around the hydrogen ...liquefaction temperature, the lack of MR materials with high magnetic entropy change in a wide temperature range required for the hydrogen liquefaction is a bottle-neck for practical applications of MR cooling systems. Here, we show a series of materials with a giant magnetocaloric effect (MCE) in magnetic entropy change (-∆S
> 0.2 J cm
K
) in the Er(Ho)Co
-based compounds, suitable for operation in the full temperature range required for hydrogen liquefaction (20-77 K). We also demonstrate that the giant MCE becomes reversible, enabling sustainable use of the MR materials, by eliminating the magneto-structural phase transition that leads to deterioration of the MCE. This discovery can lead to the application of Er(Ho)Co
-based alloys for the hydrogen liquefaction using MR cooling technology for the future green fuel society.
Cancer of unknown primary (CUP) has a poor prognosis. Given the recent approval of immune checkpoint inhibitors for several cancer types, we carried out a multicenter phase II study to assess the ...efficacy of nivolumab for patients with CUP.
Patients with CUP who were previously treated with at least one line of systemic chemotherapy constituted the principal study population. Previously untreated patients with CUP were also enrolled for exploratory analysis. Nivolumab (240 mg/body) was administered every 2 weeks for up to 52 cycles. The primary endpoint was objective response rate in previously treated patients as determined by blinded independent central review according to RECIST version 1.1.
Fifty-six patients with CUP were enrolled in the trial. For the 45 previously treated patients, objective response rate was 22.2% 95% confidence interval (CI), 11.2% to 37.1%, with a median progression-free survival and overall survival of 4.0 months (95% CI, 1.9-5.8 months) and 15.9 months (95% CI, 8.4-21.5 months), respectively. Similar clinical benefits were also observed in the 11 previously untreated patients. Better clinical efficacy of nivolumab was apparent for tumors with a higher programmed death-ligand 1 expression level, for those with a higher tumor mutation burden, and for microsatellite instability-high tumors. In contrast, no differences in efficacy were apparent between tumor subgroups based on estimated tissue of origin. Adverse events were consistent with the known safety profile of nivolumab. No treatment-related death was observed.
Our results demonstrate a clinical benefit of nivolumab for patients with CUP, suggesting that nivolumab is a potential additional therapeutic option for CUP.
•Nivolumab demonstrated clinical benefits in a statistically assessable number of patients with CUP.•Objective response rate was 22.2% in previously treated patients with CUP, which met the study primary endpoint.•Benefits were more apparent in patients with known biomarkers for ICIs, but also observed in those without such markers.•No differences in efficacy were apparent between tumor subgroups based on estimated tissue of origin.•Nivolumab could be an additional therapeutic option for these unmet medical needs.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The ubiquitin-proteasome system is central in the regulation of cellular proteins controlling cell cycle progression and apoptosis, drawing much interest for developing effective targeted cancer ...therapies. Herein, we developed a novel pH-responsive polymeric-micelle-based carrier system to effectively deliver the proteasome inhibitor MG132 into cancer cells. MG132 is covalently bound to the block copolymer composed of polyethylene glycol (PEG) and polyaspartate through an acid-labile hydrazone bond. This bond is stable at physiological condition, but hydrolytically degradable in acidic compartments in the cell, such as late-endosomes and lysosomes, and thus, it was used for controlled release of MG132 after EPR-mediated preferential accumulation of the micelles into the tumor. MG132-loaded micelles have monodispersed size distribution with an average diameter of 45nm, and critical micelle concentration is well below 10(-7)M. In vitro studies against several cancer cell lines confirmed that MG132-loaded micelles retained the cytotoxic effect, and this activity was indeed due to the inhibition of proteasome by released MG132 from the micelles. Real-time in vitro confocal-microscopy experiments clearly indicated that MG132-conjugated micelles disintegrated only inside the target cells. By intravital confocal micro-videography, we also confirmed the prolonged circulation of MG132 loaded micelles in the bloodstream, which lead to tumor specific accumulation of micelles, as confirmed by in vivo imaging 24h after injection. These micelles showed significantly lower in vivo toxicity than free MG132, while achieving remarkable antitumor effect against a subcutaneous HeLa-luc tumor model. Our findings create a paradigm for future development of polymeric-micelle-based carrier system for other peptide aldehyde type proteasome inhibitors to make them effective cohort of the existing cancer therapeutic regiments.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
The coarsening behavior of the Al3Sc particles in Al-0.2wt%Sc alloy at 673-763 K is studied on the basis of TEM observations with the numerical model. Emphasis is on the effects of ...coherent/semi-coherent transition of the particles. The radius for coherent/semi-coherent transition of the Al3Sc particles is determined from TEM micrographs as 15-40 nm. The average particle radius, rave, of the Al3Sc particles obeys the rave3 growth low both in the coherent stage (rave < 15 nm) and semi-coherent stage (rave > 40 nm). However, in the intermediate stage, where coherent and semi-coherent particles coexist (15 < rave < 40 nm), coarsening is delayed and particle size distribution is broadened in the experiment and also in the calculation. These results are qualitatively understood in consideration of the different growth rates of individual particles in the intermediate stage.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
The arrangement of sugars in glycopolymers contributes to their recognition. The molecular recognition of proteins was controlled by the living radical polymerization of glycopolymers. The ...glycopolymers were prepared by the copolymerization of propargyl methacrylate (Pr-MA) and triethyleneglycol methacrylate (TEG-MA) via living radical polymerization with a reversible addition-fragmentation glycopolymer chain transfer (RAFT) reagent and by subsequent sugar conjugation by click chemistry. The block copolymers were prepared by the polymerization of Pr-MA and TEG-MA. The molecular recognition of glycopolymers was analyzed using the fluorescence quenching of lectin and found to be dependent on the glycopolymer structures. Two-site binding of glycopolymers to concanavalin A (ConA) was attained by both the glycopolymer with a 105-mer and the tri-block glycopolymer with a 103-mer. Glycopolymers with either a 27- or 54-mer showed much weaker interaction because of one-site binding. The molecular recognition of the glycopolymer was controlled by the arrangement and size of the sugar cluster and not by the sugar density.
We report an enhancement of the anomalous Nernst effect (ANE) in Ni/Pt (001) epitaxial superlattices. The transport and magnetothermoelectric properties were investigated for the Ni/Pt superlattices ...with various Ni layer thicknesses (t). The anomalous Nernst coefficient was increased up to more than 1 μ V K−1 for 2.0 nm ≤ t ≤ 4.0 nm , which was the remarkable enhancement compared to the bulk Ni. It has been found that the large transverse thermoelectric conductivity (αxy) , reaching αxy = 4.8 A K−1 m−1 for t = 4.0 nm , plays a prime role for the enhanced ANE of the Ni/Pt (001) superlattices.
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In this Letter, we report analyses of spatiotemporal dynamics of turbulence and structure in the limit-cycle oscillation (LCO) that precedes an L-to-H transition. Zonal flows are not observed during ...LCO, and the oscillation is the periodic generations or decays of barrier with edge-localized mean flow. Oscillatory Reynolds stress is found to be too small to accelerate the LCO flow, by considering the dielectric constant in magnetized toroidal plasmas. Propagation of changes of the density gradient and turbulence amplitude into the core is also observed.
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