Polymer Micelle Formulation for the Proteasome Inhibitor Drug Carfilzomib: Anticancer Efficacy and Pharmacokinetic Studies in Mice

Carfilzomib (CFZ) is a peptide epoxyketone proteasome inhibitor approved for the treatment of multiple myeloma (MM). Despite the remarkable efficacy of CFZ against MM, the clinical trials in patients with solid cancers yielded rather disappointing results with minimal clinical benefits. Rapid degradation of CFZ in vivo and its poor penetration to tumor sites are considered to be major factors limiting its efficacy against solid cancers. We previously reported that polymer micelles (PMs) composed of biodegradable block copolymers poly(ethylene glycol) (PEG) and poly(caprolactone) (PCL) can improve the metabolic stability of CFZ in vitro. Here, we prepared the CFZ-loaded PM, PEG-PCL-deoxycholic acid (CFZ-PM) and assessed its in vivo anticancer efficacy and pharmacokinetic profiles. Despite in vitro metabolic protection of CFZ, CFZ-PM did not display in vivo anticancer efficacy in mice bearing human lung cancer xenograft (H460) superior to that of the clinically used cyclodextrin-based CFZ (CFZ-CD) formulation. The plasma pharmacokinetic profiles of CFZ-PM were also comparable to those of CFZ-CD and the residual tumors that persisted in xenograft mice receiving CFZ-PM displayed an incomplete proteasome inhibition. In summary, our results showed that despite its favorable in vitroperformances, the current CFZ-PM formulation did not improve in vivo anticancer efficacy and accessibility of active CFZ to solid cancer tissues over CFZ-CD. Careful consideration of the current results and potential confounding factors may provide valuable insights into the future efforts to validate the potential of CFZ-based therapy for solid cancer and to develop effective CFZ delivery strategies that can be used to treat solid cancers

A Study on Mechanisms for Benefit-sharing of Biodiversity and Related Knowledge: With Reference to Case Studies on Geographical Indications and Trademarks

This study reviews the innovative use of some legal tools to support the efforts of the people of local and indigenous communities to conserve and use sustainably their biological diversity, biological resources, and related traditional knowledge. So, this study reviews concepts of intellectual property- in particular geographical indications and trademarks- as possible incentives for the marketing of products from biological resources produced through traditional and environmentally friendly methods. It includes case studies: Kava, Rooibos, Quinoa, Basmati rice and Neem. Through the case studies, this study will review two forms of intellectual property rights, which have received relatively little attention in discussions of sustainable use or benefit-sharing derived from bioresources and traditional knowledge. Conclusionally, geographical indications and trademarks could potentially serve as tools to help holders of traditional knowledge benefit more equitable for the commercial use of their knowledge

A Study on International Regulations of Plant Genetic Resources

Plant Genetic Resources(PGR) are essential to our life and human being depends on PGR for all his or her conveniences, clothes, foods, houses and emotion etc. Historically, the principle of common heritage of mankind was prevailed in international practice on PGR. But, that concept has shifted from the common heritage of mankind to the principle of national sovereignty and common concern of humankind since the adoption of Convention on Biological Diversity(CBD). This article aims at the introduction of alternative solutions for access to plant genetic resources and benefit-sharing of that use. So, this article review the international conventions on plant genetic resources, which are International Undertaking on PGR, International Treaty on Plant Genetic Resources for Food and Agriculture, Convention on Biological Diversity, Bonn Guidelines, International Convention for the Protection of New Varieties of Plants(UPOV Convention) and Trade-Related Aspects of Intellectual Property Rights Agreement(TRIPs Agreement)

Object-stable unsupervised dual contrastive learning image-to-image translation with query-selected attention and convolutional block attention module.

Recently, contrastive learning has gained popularity in the field of unsupervised image-to-image (I2I) translation. In a previous study, a query-selected attention (QS-Attn) module, which employed an attention matrix with a probability distribution, was used to maximize the mutual information between the source and translated images. This module selected significant queries using an entropy metric computed from the attention matrix. However, it often selected many queries with equal significance measures, leading to an excessive focus on the background. In this study, we proposed a dual-learning framework with QS-Attn and convolutional block attention module (CBAM) called object-stable dual contrastive learning generative adversarial network (OS-DCLGAN). In this paper, we utilize a CBAM, which learns what and where to emphasize or suppress, thereby refining intermediate features effectively. This CBAM was integrated before the QS-Attn module to capture significant domain information for I2I translation tasks. The proposed framework outperformed recently introduced approaches in various I2I translation tasks, showing its effectiveness and versatility. The code is available at https://github.com/RedPotatoChip/OSUDL

Development and validation of multiphysics PWR core simulator KANT

KANT (KAIST Advanced Nuclear Tachygraphy) is a PWR core simulator recently developed at Korea Advance Institute of Science and Technology, which solves three-dimensional steady-state and transient multigroup neutron diffusion equations under Cartesian geometries alongside the incorporation of thermal-hydraulics feedback effect for multi-physics calculation. It utilizes the standard Nodal Expansion Method (NEM) accelerated with various Coarse Mesh Finite Difference (CMFD) methods for neutronics calculation. For thermal-hydraulics (TH) calculation, a single-phase flow model and a one-dimensional cylindrical fuel rod heat conduction model are employed. The time-dependent neutronics and TH calculations are numerically solved through an implicit Euler scheme, where a detailed coupling strategy is presented in this paper alongside a description of nodal equivalence, macroscopic depletion, and pin power reconstruction. For validation of the steady, transient, and depletion calculation with pin power reconstruction capacity of KANT, solutions for various benchmark problems are presented. The IAEA 3-D PWR and 4-group KOEBERG problems were considered for the steady-state reactor benchmark problem. For transient calculations, LMW (Lagenbuch, Maurer and Werner) LWR and NEACRP 3-D PWR benchmarks were solved, where the latter problem includes thermal-hydraulics feedback. For macroscopic depletion with pin power reconstruction, a small PWR problem modified with KAIST benchmark model was solved. For validation of the multi-physics analysis capability of KANT concerning large-sized PWRs, the BEAVRS Cycle1 benchmark has been considered. It was found that KANT solutions are accurate and consistent compared to other published works

Electrocatalysts composed of a Co(acetylacetonate)(2) molecule and refluxed graphene oxide for an oxygen reduction reaction

Hybridization of organometallic complexes with carbon-based materials has been shown to enhance the catalytic performance in the oxygen reduction reaction (ORR). As chemical interactions between the metal centers and ligands are critical factors determining their tunable catalytic nature, it is important to understand the correlation between the chemical structure and catalytic nature and the correlation between the chemical structure and catalytic performance of the hybrids. In this work, the hybrids are synthesized by the reaction of an organometallic complex, Co(II)(acac)(2) (acac = acetylacetonate), with refluxed graphene oxide (Re-G-O) materials containing controlled amounts of oxygen atoms at room temperature. Experimental characterization of the hybrids reveals that Co(II)(acac)(2) is coordinated to oxygen containing groups in Re-G-O, generating organometallic species, Co-O-4-O. These hybrids showed better electrocatalytic activity for the ORR in alkaline media than Co-free Re-G-O materials. The results show that the Co-O-4 species is catalytically active for the ORR. We find that the best Co-O-4 catalyst for the ORR is produced by the use of reduced graphene oxide with a medium level of reduction

Formation of buried superconducting Mo2N by nitrogen-ion-implantation

Nitrogen ion implantation is a useful technique to put nitrogen ions into lattices. In this work, nitrogen ion implantation into epitaxial Mo films is performed to create a buried superconducting gamma-Mo2N. Atomically flat epitaxial (110) Mo films are grown on (0001) Al2O3. By impinging nitrogen ions, where the beam energy is fixed to 20 keV, we observe (111) gamma-Mo2N diffraction and the formation of a gamma-Mo2N layer from X-ray reflectivity. Magnetization and transport measurements clearly support a superconducting layer in the implanted film. Our strategy shows that formation of a buried superconducting layer can be achieved through ion implantation and self-annealing

Hemodialysis as a Risk Factor for Lower Right Internal Jugular Stenosis in Cardiac Surgery Patients: A Retrospective Single-Center Study

Lower right internal jugular vein (RIJ) stenosis has been reported as a common cause of RIJ catheterization failure. However, the risk factors for lower RIJ stenosis in patients undergoing cardiac surgery is unclear. We reviewed the electronic medical records of all adult patients who had undergone cardiac operations in a single tertiary university hospital from January 2014 to January 2016. Patients were excluded if they were lack of preoperative contrast-enhanced chest computed tomography (CT) studies. Lower RIJ stenosis was defined as a ratio of cross-sectional area at the smallest level to cross-sectional area at the largest level less than 25%. Multivariable logistic regression analyses were used to investigate the risk factors for lower RIJ stenosis. A sensitivity analysis was also conducted using a cross-sectional area ratio of under 20%. The analysis included 889 patients, and the incidence of lower RIJ stenosis was 3.9%. The multivariable logistic regression analyses revealed that hemodialysis was an independent risk factor for lower RIJ stenosis (OR, 3.54; 95% CI, 1.472–8.514). Sensitivity analysis provided that hemodialysis (OR, 10.842; 95% CI, 3.589–32.75) was a significant predictor of cross-sectional area ratio <20%. Preoperative hemodialysis are significantly associated with an increased risk of lower RIJ stenosis in patients undergoing cardiac surgery. Extra care is needed during central venous catheterization in hemodialysis patients undergoing cardiac surgery