Results Visualization in the XBrain XML Interface to a Relational Database

The University of Washington's XBrain application is used to dynamically export relational data over the web in XML format, as a prelude to data exchange. We describe additional tools to aid the human user in visualizing the dynamically generated XML results returned by the web application

Cross-aisle seismic performance of selective storage racks

© 2020 A series of single-axis shaking table tests were conducted on three full-scale selective storage racks in the cross-aisle direction. The uplifting and rocking behaviour of the racks was examined under three baseplate types: ductile, heavy duty, and unanchored. Each rack was subjected to a sequence of ground motions of increasing intensity up to failure, with a total of 29 tests conducted. At 1.5 times the respective design level ground motions, the heavy duty baseplates caused a foundation failure while the unanchored rack failed by overturning. The rack with ductile baseplates survived all tests up to 2.3 times the design level. For a given ground motion, the unanchored rack upright always had the smallest peak axial load. However, the unanchored rack had much larger sways under the Northbridge and Kobe ground motions. The NZS 1170.5 equivalent static method design loading was found to be overly conservative for racks with ductile and heavy duty baseplates, of which the upright design axial forces were better predicted using the refined equivalent static method

Oral delivery of camptothecin using cyclodextrin/poly(anhydride) nanoparticles

Camptothecin (CPT), a molecule that shows powerful anticancer activity, is still not used in clinic due to its high hydrophobicity and poor active form's stability. In order to solve these drawbacks, the combination between poly(anhydride) nanoparticles and cyclodextrins was evaluated. CPT-loaded nanoparticles, prepared in the presence of 2-hydroxypropyl-β-cyclodextrin, (HPCD-NP) displayed a mean size close to 170nm and a payload of 50μg per mg (25 times higher than the one of the control nanoparticles). CPT was not released from nanoparticles under gastric conditions. However, under intestinal conditions, about 50% of the drug content was released as a burst, whereas the remained drug was released following a zero-order kinetic. Pharmacokinetic studies revealed that the CPT plasma levels, from orally administered nanoparticles, were high and sustained up to 48h. The CPT oral bioavailability was 7-fold higher than the value obtained with the control, whereas its clearance was significantly lower than for the aqueous suspension. These observations may be directly related to a prolonged residence time of nanoparticles in close contact with the intestinal epithelium, the presence of the cyclodextrin that decreases the CPT transformation into its inactive form and the generation of an acidic microenvironment during the degradation of the poly(anhydride) that would prevent the transformation of the active lactone into the inactive carboxylate conformation

Tailoring the supramolecular structure of amphiphilic glycopolypeptide analogue toward liver targeted drug delivery systems

Amphiphilic glycopolypeptide analogues have harboured great importance in the development of targeted drug delivery systems. In this study, lactosylated pullulan-graft-arginine dendrons (LP-g-G3P) was synthesized using Huisgen azide-alkyne 1,3-dipolar cycloaddition between lactosylated pullulan and generation 3 arginine dendrons bearing Pbf and Boc groups on the periphery. Hydrophilic lactosylated pullulan was selected for amphiphilic modification, aiming at specific lectin recognition. Macromolecular structure of LP-g-G3P combined alkyl, aromatic, and peptide dendritic hydrophobic moieties and was able to self-assemble spontaneously into core-shell nanoarchitectures with small particle sizes and low polydispersity in the aqueous media, which was confirmed by CAC, DLS and TEM. Furthermore, the polyaromatic anticancer drug (doxorubicin, DOX) was selectively encapsulated in the hydrophobic core through multiple interactions with the dendrons, including π-π interactions, hydrogen bonding and hydrophobic interactions. Such multiple interactions had the merits of enhanced drug loading capacity (16.89 ± 2.41%), good stability against dilution, and excellent sustained release property. The cell viability assay presented that LP-g-G3P nanoparticles had an excellent biocompatibility both in the normal and tumor cells. Moreover, LP-g-G3P/DOX nanoparticles could be effectively internalized into the hepatoma carcinoma cells and dramatically inhibited cell proliferation. Thus, this approach paves the way to develop amphiphilic and biofunctional glycopolypeptide-based drug delivery systems.the European Commission Research and Innovation (PIRSES-GA-2011-295218

Simultaneous extraction and purification of alkaloids from Sophora flavescens Ait. by microwave-assisted aqueous two-phase extraction with ethanol/ammonia sulfate system

A rapid and effective method of integrating extraction and purification for alkaloids from Sophora flavescens Ait. was developed by microwave-assisted aqueous two-phase extraction (MAATPE) based on the high efficiency of microwave-assisted extraction (MAE) and the demixing effect of aqueous two-phase extraction (ATPE). The aqueous two-phase system (ATPS), ethanol/ammonia sulfate was chosen from seven combinations of ethanol/salt systems, and its extraction properties were investigated in detail. Key factors, namely, the compositions of ATPS, solvent-to-materials ratio, and the extraction temperature were selected for optimization of the experimental conditions using response surface methodology (RSM) on the basis of the results of the single-factor experiment. The final optimized conditions were, the compositions of ATPS: ethanol 28% (w/w) and (NH4)2SO4 18% (w/w), solvent-to-material ratio 60:1, temperature 90 C, extraction time 5 min, and microwave power 780 W. MAATPE was superior to MAE, the latter using a single solvent, not only in extraction yield but also in impurity content. Moreover, compared with the combination of MAE and ATPE in the two-step mode, MAATP demonstrated fewer impurities, a better yield (63.78 ± 0.45 mg/g) and a higher recovery (92.09 ± 0.14%) in the extraction and purification of alkaloids. A continuous multiphase-extraction model of MAATPE was proposed to explicate the extraction mechanism. MAATPE revealed that the interaction between microwave and ATPS cannot only cause plant cell rupture but also accelerate demixing, improving mass-transfer from solid–liquid extraction to liquid– liquid purification. MAATPE simplified procedures also contributed to the lower loss occurrence, better extraction efficiency, and reduced impurity to target constituents.The Science and Technology Project of Guangzhou (No. 2008Z1-E301) and Faculty Development fund Project of Guangdong Pharmaceutical University (No. 52104109

Synthesis of electroneutralized amphiphilic copolymers with peptide dendrons for intramuscular gene delivery

Intramuscular gene delivery materials are of great importance in plasmid-based gene therapy system, but there is limited information so far on how to design and synthesize them. A previous study showed that the peptide dendron-based triblock copolymer with its components arranged in a reversed biomembrane architecture could significantly increase intramuscular gene delivery and expression. Herein, we wonder whether copolymers with biomembrane-mimicking arrangement may have similar function on intramuscular gene delivery. Meanwhile, it is of great significance to uncover the influence of electric charge and molecular structure on the function of the copolymers. To address the issues, amphiphilic triblock copolymers arranged in hydrophilic-hydrophobic-hydrophilic structure were constructed despite the paradoxical characteristics and difficulties in synthesizing such hydrophilic but electroneutral molecules. The as-prepared two copolymers, dendronG2(l-lysine-OH)-poly propylene glycol2k(PPG2k)-dendronG2(l-lysine-OH) (rL2PL2) and dendronG3(l-lysine-OH)-PPG2k-dendronG3(l-lysine-OH) (rL3PL3), were in similar structure but had different hydrophilic components and surface charges, thus leading to different capabilities in gene delivery and expression in skeletal muscle. rL2PL2 was more efficient than Pluronic L64 and rL3PL3 when mediating luciferase, β-galactosidase, and fluorescent protein expressions. Furthermore, rL2PL2-mediated growth-hormone-releasing hormone expression could significantly induce mouse body weight increase in the first 21 days after injection. In addition, both rL2PL2 and rL3PL3 showed good in vivo biosafety in local and systemic administration. Altogether, rL2PL2-mediated gene expression in skeletal muscle exhibited applicable potential for gene therapy. The study revealed that the molecular structure and electric charge were critical factors governing the function of the copolymers for intramuscular gene delivery. It can be concluded that, combined with the previous study, both structural arrangements either reverse or similar to the biomembrane are effective in designing such copolymers. It also provides an innovative way in designing and synthesizing new electroneutralized triblock copolymers, which could be used safely and efficiently for intramuscular gene delivery

Electric Field-Tuned Topological Phase Transition in Ultra-Thin Na3Bi - Towards a Topological Transistor

The electric field induced quantum phase transition from topological to conventional insulator has been proposed as the basis of a topological field effect transistor [1-4]. In this scheme an electric field can switch 'on' the ballistic flow of charge and spin along dissipationless edges of the two-dimensional (2D) quantum spin Hall insulator [5-9], and when 'off' is a conventional insulator with no conductive channels. Such as topological transistor is promising for low-energy logic circuits [4], which would necessitate electric field-switched materials with conventional and topological bandgaps much greater than room temperature, significantly greater than proposed to date [6-8]. Topological Dirac semimetals(TDS) are promising systems in which to look for topological field-effect switching, as they lie at the boundary between conventional and topological phases [3,10-16]. Here we use scanning probe microscopy/spectroscopy (STM/STS) and angle-resolved photoelectron spectroscopy (ARPES) to show that mono- and bilayer films of TDS Na3Bi [3,17] are 2D topological insulators with bulk bandgaps >400 meV in the absence of electric field. Upon application of electric field by doping with potassium or by close approach of the STM tip, the bandgap can be completely closed then re-opened with conventional gap greater than 100 meV. The large bandgaps in both the conventional and quantum spin Hall phases, much greater than the thermal energy kT = 25 meV at room temperature, suggest that ultrathin Na3Bi is suitable for room temperature topological transistor operation

Interactions among mitochondrial proteins altered in glioblastoma

Mitochondrial dysfunction is putatively central to glioblastoma (GBM) pathophysiology but there has been no systematic analysis in GBM of the proteins which are integral to mitochondrial function. Alterations in proteins in mitochondrial enriched fractions from patients with GBM were defined with label-free liquid chromatography mass spectrometry. 256 mitochondrially-associated proteins were identified in mitochondrial enriched fractions and 117 of these mitochondrial proteins were markedly (fold-change ≥2) and significantly altered in GBM (p ≤ 0.05). Proteins associated with oxidative damage (including catalase, superoxide dismutase 2, peroxiredoxin 1 and peroxiredoxin 4) were increased in GBM. Protein–protein interaction analysis highlighted a reduction in multiple proteins coupled to energy metabolism (in particular respiratory chain proteins, including 23 complex-I proteins). Qualitative ultrastructural analysis in GBM with electron microscopy showed a notably higher prevalence of mitochondria with cristolysis in GBM. This study highlights the complex mitochondrial proteomic adjustments which occur in GBM pathophysiology