Highly stable core-surface-crosslinked nanoparticles as cisplatin carriers for cancer chemotherapy

Cisplatin is a potent anticancer drug with low solubility in water. A new type of highly stable polymer micelles, namely core-surface-crosslinked nanoparticles (SCNPs) made from amphiphilic brush copolymers, were evaluated as the carrier of cisplatin. Cisplatin could be loaded in the SCNPs with poly(varepsilon-caprolactone) (PCL) cores and hydrophilic poly(ethylene glycol) (PEG) or poly[2-(N,N-dimethylamino)ethyl methacrylate] (PDMA) shells with high loading efficiency (approximately 90%). In vitro cellular uptake experiments indicated that both SCNPs could be easily taken up by SKOV-3 ovarian cancer cells. Both cell proliferation assay and IC50 measurements indicated that cisplatin encapsulated in the SCNPs had much enhanced cytotoxicity to the cancer cells compared to free cisplatin. The positive charges on the PCL/PDMA SCNPs promoted the cellular internalization of the nanoparticles, resulting in higher cytotoxicity of cisplatin in these SCNPs. The IC50 of the cisplatin encapsulated in PCL/PDMA SCNPs was as low as 0.01 microg/mL, lower than that of cisplatin in PCL/PEG SCNPs and free cisplatin.     

Immobilization of ligands with precise control of density to electroactive surfaces

We report a broadly applicable surface chemistry methodology to immobilize ligands, proteins, and cells to an electroactive substrate with precise control of ligand density. This strategy is based on the coupling of soluble aminooxy terminated ligands with an electroactive quinone terminated monolayer. The surface chemistry product oxime is also redox active but at a different potential and therefore allows for real-time monitoring of the immobilization reaction. Only the quinone form of the immobilized redox pair is reactive with soluble aminooxy groups, which allows for the determination of the yield of reaction, the ability to immobilize multiple ligands at controlled densities, and the in-situ modulation of ligand activity. We demonstrate this methodology by using cyclic voltammetry to characterize the kinetics of a model interfacial reaction with aminooxy acetic acid. We also demonstrate the synthetic flexibility and utility of this method for biospecific interactions by installing aminooxy terminated FLAG peptides and characterizing their binding to soluble anti-FLAG with surface plasmon resonance spectroscopy. We further show this methodology is compatible with microarray technology by printing rhodamine-oxyamine in various size spots and characterizing the yield within the spots by cyclic voltammetry. We also show this methodology is compatible with cell culture conditions and fluorescent microscopy technology for cell biological studies. Arraying RGD-oxyamine peptides on these substrates allows for bio-specific adhesion of Swiss 3T3 Fibroblasts.     

Hyperinols A and B, chymotrypsin inhibiting triterpenes from Hypericum oblongifolium

Hyperinols A (1) and B (2) are new taraxastane type triterpenes which have been isolated from the chloroform soluble fraction of Hypericum oblongifolium and their structures elucidated on the basis of spectroscopic data. Both showed significant inhibitory activity against chymotrypsin enzyme.     

Modeling auditory-nerve responses for high sound pressure levels in the normal and impaired auditory periphery

This paper presents a computational model to simulate normal and impaired auditory-nerve (AN) fiber responses in cats. The model responses match physiological data over a wider dynamic range than previous auditory models. This is achieved by providing two modes of basilar membrane excitation to the inner hair cell (IHC) rather than one. The two modes are generated by two parallel filters, component 1 (C1) and component 2 (C2), and the outputs are subsequently transduced by two separate functions. The responses are then added and passed through the IHC low-pass filter followed by the IHC-AN synapse model and discharge generator. The C1 filter is a narrow-band, chirp filter with the gain and bandwidth controlled by a nonlinear feed-forward control path. This filter is responsible for low and moderate level responses. A linear, static, and broadly tuned C2 filter followed by a nonlinear, inverted and nonrectifying C2 transduction function is critical for producing transition region and high-level effects. Consistent with Kiang's two-factor cancellation hypothesis, the interaction between the two paths produces effects such as the C1/C2 transition and peak splitting in the period histogram. The model responses are consistent with a wide range of physiological data from both normal and impaired ears for stimuli presented at levels spanning the dynamic range of hearing.     

Exact Analysis of Level-Crossing Statistics for (d+1)-Dimensional Fluctuating Surfaces

We carry out an exact analysis of the average frequency ν⁺ _αxi in the direction x _i of positiveslope crossing of a given level α such that, h(x, t) − = α, of growing surfaces in spatial dimension d. Here, h(x, t) is the surface height at time t, and is its mean value. We analyze the problem when the surface growth dynamics is governed by the Kardar-Parisi-Zhang (KPZ) equation without surface tension, in the time regime prior to appearance of cusp singularities (sharp valleys), as well as in the random deposition (RD) model. The total number N ⁺ of such level-crossings with positive slope in all the directions is then shown to scale with time as t ^d/2 for both the KPZ equation and the RD model. PACS number(s): 52.75.Rx, 68.35.Ct     

Cohen-Macaulay monomial ideals with given radical

We study the set of Cohen-Macaulay monomial ideals with a given radical. Among this set of ideals are the so-called Cohen-Macaulay modifications. Not all Cohen-Macaulay squarefree monomial ideals admit nontrivial Cohen-Macaulay modifications. It is shown that if there exists one such modification, then there exist indeed infinitely many.     

Exp-function method for traveling wave solutions of nonlinear evolution equations

In this paper, we apply the exp-function method to construct generalized solitary and periodic solutions of nonlinear evolution equations. The proposed technique is tested on the modified Zakharov-Kuznetsov (ZK) and Zakharov-Kuznetsov-Modified-Equal-Width (ZK-MEW) equations. These equations play a very important role in mathematical physics and engineering sciences. The suggested algorithm is quite efficient and is practically well suited for use in these problems. Numerical results clearly indicate the reliability and efficiency of the proposed exp-function method.     

Modified Extragradient Methods for a System of Variational Inequalities in Banach Spaces

In this paper, we introduce a new system of general variational inequalities in Banach spaces. We establish the equivalence between this system of variational inequalities and fixed point problems involving the nonexpansive mapping. This alternative equivalent formulation is used to suggest and analyze a modified extragradient method for solving the system of general variational inequalities. Using the demi-closedness principle for nonexpansive mappings, we prove the strong convergence of the proposed iterative method under some suitable conditions.