Targeted Polymersome Delivery of siRNA Induces Cell Death of Breast Cancer Cells Dependent upon Orai3 Protein Expression

Polymersomes, polymeric vesicles that self-assemble in aqueous solutions from block copolymers, have been avidly investigated in recent years as potential drug delivery agents. Past work has highlighted peptide-functionalized polymersomes as a highly promising targeted delivery system. However, few reports have investigated the ability of polymersomes to operate as gene delivery agents. In this study, we report on the encapsulation and delivery of siRNA inside of peptide-functionalized polymersomes composed of poly(1,2-butadiene)-b-poly(ethylene oxide). In particular, PR_b peptide-functionalized polymer vesicles are shown to be a promising system for siRNA delivery. PR_b is a fibronectin mimetic peptide targeting specifically the α(5)β(1) integrin. The Orai3 gene was targeted for siRNA knockdown, and PR_b-functionalized polymer vesicles encapsulating siRNA were found to specifically decrease cell viability of T47D breast cancer cells to a certain extent, while preserving viability of noncancerous MCF10A breast cells. siRNA delivery by PR_b-functionalized polymer vesicles was compared to that of a current commercial siRNA transfection agent, and produced less dramatic decreases in cancer cell viability, but compared favorably in regards to the relative toxicity of the delivery systems. Finally, delivery and vesicle release of a fluorescent encapsulate by PR_b-functionalized polymer vesicles was visualized by confocal microscopy, and colocalization with cellular endosomes and lysosomes was assessed by organelle staining. Polymersomes were observed to primarily release their encapsulate in the early endosomal intracellular compartments, and data may suggest some escape to the cytosol. These results represent a promising first generation model system for targeted delivery of siRNA.     

Corylucinine, a new alkaloid from Corydalis cava (Fumariaceae), and its cholinesterase activity

A new benzyldihydroisoquinoline alkaloid (1) was isolated from the tubers of Corydalis cava and named corylucinine. Additionally, 8-trichloromethyl-7,8-dihydropalmatine (2), an isolation artifact of tetrahydropalmatine, was obtained. The structures were established by spectroscopic (including 2D NMR and optical rotation) and HR-ESI-MS methods. Both compounds were tested for human blood acetylcholinesterase (HuAChE) and human plasma butyrylcholinesterase (HuBuChE) inhibitory activity. In comparison with the used standards, both compounds showed only moderate inhibitory activity against HuAChE (IC50,. HuAChE = 127.6 +/- 5.2 microM for 1, and IC50, HuAChE = 82.9 +/- 3.9 microM for 2) and none against HuBuChE.     

On the breakdown of the uniqueness of a solution of the Dirichlet problem for typeless differential equations of arbitrary even order in a disk

The nontrivial solvability of the homogeneous Dirichlet problem in a unit disk $ K\subset {{\mathbb{R}}^2} $ in positive Sobolev spaces is studied for a typeless differential equation of arbitrary even order 2m, m ≥ 2, with constant complex-valued coefficients and homogeneous symbol. The detailed proofs of the criteria of nontrivial solvability of the problem are given in various cases that form a complete picture. The example considered by A. V. Bitsadze is generalized for the equations of arbitrary even order 2m, m ≥ 2.     

Connecting mathematical creativity to mathematical ability

This study aims to investigate whether there is a relationship between mathematical ability and mathematical creativity, and to examine the structure of this relationship. Furthermore, in order to validate the relationship between the two constructs, we will trace groups of students that differ across mathematical ability and investigate the relationships amongst these students’ performance on a mathematical ability test and the components of mathematical creativity. Data were collected by administering two tests, a mathematical ability and a mathematical creativity test, to 359 elementary school students. Mathematical ability was considered as a multidimensional construct, including quantitative ability (number sense and pre-algebraic reasoning), causal ability (examination of cause–effect relations), spatial ability (paper folding, perspective and spatial rotation abilities), qualitative ability (processing of similarity and difference relations) and inductive/deductive ability. Mathematical creativity was defined as a domain-specific characteristic, enabling individuals to be characterized by fluency, flexibility and originality in the domain of mathematics. The data analysis revealed that there is a positive correlation between mathematical creativity and mathematical ability. Moreover, confirmatory factor analysis suggested that mathematical creativity is a subcomponent of mathematical ability. Further, latent class analysis showed that three different categories of students can be identified varying in mathematical ability. These groups of students varying in mathematical ability also reflected three categories of students varying in mathematical creativity.     

Raman spectroscopic identification of usnic acid in hydrothermal minerals as a potential Martian analogue

Raman spectroscopy using 785 nm excitation was tested as a nondestructive method for determining the presence of the potential biomarker, usnic acid, in experimentally prepared mineral matrices. Investigated samples consisting of usnic acid mixed with powdered hydrothermal minerals, gypsum and calcite were studied. Various concentrations of usnic acid in the mineral matrix were studied to determine the detection limits of this biomarker. Usnic acid was mixed with gypsum (respectively, calcite) and covered by a UV-transparent crystal of gypsum (CaSO(4) x 2 H(2)O), thereby creating artificial inclusions similar to those which could be present in Martian minerals. A Raman usnic acid signal at the concentration level as low as 1 g kg(-1) was obtained in the powdered mineral matrix and 5 g kg(-1) when analyzed through the monocrystal. The number of registered usnic acid key Raman bands was dependent on the particular mineral matrix. If a similar concentration of usnic acid could persist in Martian samples, then Raman spectroscopy will be able to identify it. Obtained results will aid both in situ Raman analyses on Mars and on Earth.     

Cobalt Growth on the Tips of CdSe Nanorods

Best of both worlds : Reduction of an organometallic Co precursor on preformed CdSe nanorods yields two distinct semiconducting–magnetic heterostructures (see picture). The selective growth of Co on the tips of CdSe first gives nanosphere–nanorod dimers, which evolve into nanorod–nanorod structures. In the hybrid objects the magnetic properties of Co remain intact, while the luminescence properties of CdSe are affected but not completely quenched.

     

Spatially resolved Suzuki coupling reaction initiated and controlled using a catalytic AFM probe

Appropriately modified proximal probes can be utilized in the spatially resolved chemical coupling of surface-bound and solution-phase reagents. Herein we report a chemically specific Suzuki coupling reaction between a surface-confined aryl bromide and boronic acid reagents in solution achieved using a catalytic AFM probe.     

Use of automated direct sample introduction with analyte protectants in the GC-MS analysis of pesticide residues

Automated large-volume direct sample introduction, or difficult matrix introduction (DMI), was investigated in the determination of 44 pesticide residues possessing a wide range of physico-chemical properties (volatility, polarity, pK(a)) in fruit-based baby food by means of gas chromatography-mass spectrometry (GC-MS) with a quadrupole mass analyzer. DMI has advantages over traditional injection because large volumes (up to 30 microL) of potentially dirty sample extracts can be injected into the GC-MS, but nonvolatile matrix components that would normally contaminate the inlet are removed after every injection. The extra matrix and glass surfaces involved in DMI, however, make the system more prone to the matrix-induced chromatographic enhancement effect, which adversely affects quantification of several pesticides. To overcome this problem, matrix-matched calibration standards and/or the use of analyte protectants were applied in the DMI approach, and the analysis of extracts was also compared before and after undergoing clean-up by dispersive solid-phase extraction. For best quantification, clean-up was still needed, and the combination of matrix-matching with analyte protectants gave the most reproducible results. Depending on the application, however, the addition of analyte protectants (a mixture of 3-ethoxy-1,2-propanediol, L-gulonic acid 3-lactone, and D-sorbitol) to sample extracts and calibration standards in solvent (non-matrix matched), gave satisfactory quantification for most of the 44 pesticides tested. The lowest calibration levels for 34 of the 44 pesticides were < or = 10 ng/g, which meets the standard required by the European Union Baby Food Directive (2003/13/EC).