Multipod structures of lamellae-forming diblock copolymers in three-dimensional confinement spaces: experimental observation and computer simulation

The three-dimensional (3D) confinement effect on the microphase-separated structure of a diblock copolymer was investigated both experimentally and computationally. Block copolymer nanoparticles were prepared by adding a poor solvent into a block copolymer solution and subsequently evaporating the good solvent. The 3D structures of the nanoparticles were quantitatively determined with transmission electron microtomography (TEMT). TEMT observations revealed that various complex structures, including tennis-ball, mushroom-like, and multipod structures, were formed in the 3D confinement. Detailed structural analysis, showed that one block of the diblock copolymer slightly prefers to segregate into the particle surface compared with the other block. The observed structures were further elaborated using cell dynamics computer simulatio

Recombinant methioninase combined with doxorubicin (DOX) regresses a DOX-resistant synovial sarcoma in a patient-derived orthotopic xenograft (PDOX) mouse model.

Synovial sarcoma (SS) is a recalcitrant subgroup of soft tissue sarcoma (STS). A tumor from a patient with high grade SS from a lower extremity was grown orthotopically in the right biceps femoris muscle of nude mice to establish a patient-derived orthotopic xenograft (PDOX) mouse model. The PDOX mice were randomized into the following groups when tumor volume reached approximately 100 mm3: G1, control without treatment; G2, doxorubicin (DOX) (3 mg/kg, intraperitoneal [i.p.] injection, weekly, for 2 weeks; G3, rMETase (100 unit/mouse, i.p., daily, for 2 weeks); G4 DOX (3mg/kg), i.p. weekly, for 2 weeks) combined with rMETase (100 unit/mouse, i.p., daily, for 2 weeks). On day 14 after treatment initiation, all therapies significantly inhibited tumor growth compared to untreated control, except DOX: (DOX: p = 0.48; rMETase: p < 0.005; DOX combined with rMETase < 0.0001). DOX combined with rMETase was significantly more effective than both DOX alone (p < 0.001) and rMETase alone (p < 0.05). The relative body weight on day 14 compared with day 0 did not significantly differ between any treatment group or untreated control. The results indicate that r-METase can overcome DOX-resistance in this recalcitrant disease

In silico prediction of skin metabolism and its implication in toxicity assessment

Skin, being the largest organ of the body, represents an important route of exposure, not only for the abundance of chemicals present in the environment, but also for products designed for topical application such as drugs and personal care products. Determining whether such incidental or intentional exposure poses a risk to human health requires consideration of temporal concentration, both externally and internally, in addition to assessing the chemical’s intrinsic hazard. In order to elicit a toxic response in vivo the chemical must reach its site of action in sufficient concentration, as determined by its absorption, distribution, metabolism and elimination (ADME) profile. Whilst absorption and distribution into and through skin layers have been studied for decades, only more recently has skin metabolism become a subject of intense research, now recognised as playing a key role in both toxification and detoxification processes. The majority of information on metabolic processes, however, has generally been acquired via studies performed on the liver. This paper outlines strategies that may be used to leverage current knowledge, gained from liver metabolism studies, to inform predictions for skin metabolism through understanding the differences in the enzymatic landscapes between skin and liver. The strategies outlined demonstrate how an array of in silico tools may be used in concert to resolve a significant challenge in predicting toxicity following dermal exposure. The use of in vitro methods for determining skin metabolism, both to provide further experimental data for modelling and to verify predictions is also discussed. Herein, information on skin metabolism is placed within the context of toxicity prediction for risk assessment, which requires consideration of both exposure and hazard of parent chemicals and their metabolites

Belle II Technical Design Report

The Belle detector at the KEKB electron-positron collider has collected almost 1 billion Y(4S) events in its decade of operation. Super-KEKB, an upgrade of KEKB is under construction, to increase the luminosity by two orders of magnitude during a three-year shutdown, with an ultimate goal of 8E35 /cm^2 /s luminosity. To exploit the increased luminosity, an upgrade of the Belle detector has been proposed. A new international collaboration Belle-II, is being formed. The Technical Design Report presents physics motivation, basic methods of the accelerator upgrade, as well as key improvements of the detector.Comment: Edited by: Z. Dole\v{z}al and S. Un

The Precision nEDM Measurement with UltraCold Neutrons at TRIUMF

The TRIUMF Ultra-Cold Advanced Neutron (TUCAN) collaboration aims at a precision neutron electric dipole moment (nEDM) measurement with an uncertainty of $10^{-27}\,e\cdot\mathrm{cm}$, which is an order-of-magnitude better than the current nEDM upper limit and enables us to test Supersymmetry. To achieve this precision, we are developing a new high-intensity ultracold neutron (UCN) source using super-thermal UCN production in superfluid helium (He-II) and a nEDM spectrometer. The current development status of them is reported in this article.Comment: Proceedings of the 24th International Spin Symposium (SPIN 2021), 18-22 October 2021, Matsue, Japa

Circadian Disruption Accelerates Tumor Growth and Angio/Stromagenesis through a Wnt Signaling Pathway

Epidemiologic studies show a high incidence of cancer in shift workers, suggesting a possible relationship between circadian rhythms and tumorigenesis. However, the precise molecular mechanism played by circadian rhythms in tumor progression is not known. To identify the possible mechanisms underlying tumor progression related to circadian rhythms, we set up nude mouse xenograft models. HeLa cells were injected in nude mice and nude mice were moved to two different cases, one case is exposed to a 24-hour light cycle (L/L), the other is a more “normal” 12-hour light/dark cycle (L/D). We found a significant increase in tumor volume in the L/L group compared with the L/D group. In addition, tumor microvessels and stroma were strongly increased in L/L mice. Although there was a hypervascularization in L/L tumors, there was no associated increase in the production of vascular endothelial cell growth factor (VEGF). DNA microarray analysis showed enhanced expression of WNT10A, and our subsequent study revealed that WNT10A stimulates the growth of both microvascular endothelial cells and fibroblasts in tumors from light-stressed mice, along with marked increases in angio/stromagenesis. Only the tumor stroma stained positive for WNT10A and WNT10A is also highly expressed in keloid dermal fibroblasts but not in normal dermal fibroblasts indicated that WNT10A may be a novel angio/stromagenic growth factor. These findings suggest that circadian disruption induces the progression of malignant tumors via a Wnt signaling pathway