Self-assembled virus-like particles with magnetic cores

Efficient encapsulation of functionalized spherical nanoparticles by viral protein cages was found to occur even if the nanoparticle is larger than the inner cavity of the native capsid. This result raises the intriguing possibility of reprogramming the self-assembly of viral structural proteins. The iron oxide nanotemplates used in this work are superparamagnetic, with a blocking temperature of about 250 K, making these virus-like particles interesting for applications such as magnetic resonance imaging and biomagnetic materials. Another novel feature of the virus-like particle assembly described in this work is the use of an anionic lipid micelle coat instead of a molecular layer covalently bound to the inorganic nanotemplate. Differences between the two functionalization strategies are discussed.     

Analysis and enhancement of human–machine interfaces using a joystick controller

This article deals with performance evaluation of human operations in point‐to‐point displacement tasks using a joystick. Analysis of operator outputs during an experimental task revealed a pattern of partially overlapping submovements with predictable velocity characteristics and forms. A velocity‐dependent gain control added to the joystick–cursor interface improved performance when compared to a conventional linear transformation. This control algorithm can be recommended for many similar human–machine interfaces. A specific performance evaluation was applied to estimate the characteristics of different remote control designs. This approach can be used for evaluating human–machine systems. © 2000 John Wiley & Sons, Inc.     

Starch‐capped sulphur nanoparticles synthesised from bulk powder sulphur and their anti‐phytopathogenic activity against Clavibacter sepedonicus

Water‐soluble, stable nanoparticles of elemental sulphur with a size of 9‐52 nm have been synthesised using the stabilising potential of starch. Sulphide anions were used as sulphur precursors that were generated earlier from the bulk powder sulphur in the base‐reduction system NaOH‐N₂H₄·H₂O followed by their oxidation with molecular oxygen to element sulphur atoms. Using a set of modern spectral and microscopic methods (XRD, optical spectroscopy, DLS, TEM), the phase state, elemental composition of the nanocomposites and their nanomorphological characteristics have been investigated. It was found that nanocomposites are formed as sulphur particles with the shape which is nearly spherical dispersed in the polysaccharide starch matrix with a pronounced tendency to cluster into ring formations. Water solubility and stability of the obtained nanoparticles is ensured by sorption of starch macromolecules on the surface of sulphur nanoparticles, with the thickness of the stabilising shell in a range of 10‐171 nm. In vitro experiments were carried out to study the anti‐microbial activity of the obtained sulphur nanocomposite (1.6% S) using the propidium iodide fluorescent dye staining method and the diffusion method. It showed that the water solution of the starch‐capped sulphur nanoparticles at the concentration of 6.25 µg/ml had a pronounced anti‐phytopathogenic activity against the potato ring rot pathogen Clavibacter michiganensis subsp. sepedonicus.     

Carbenoxolon Is Capable to Regulate the Mitochondrial Permeability Transition Pore Opening in Chronic Alcohol Intoxication

Background: carbenoxolone, which is a derivative of glyceretic acid, is actively used in pharmacology for the treatment of diseases of various etiologies. In addition, we have shown carbenoxolone as an effective inducer of mitochondrial permeability transition pore in rat brain and liver mitochondria. Methods: in the course of this work, comparative studies were carried out on the effect of carbenoxolone on the parameters of mPTP functioning in mitochondria isolated from the liver of control and alcoholic rats. Results: within the framework of this work, it was found that carbenoxolone significantly increased its effect in the liver mitochondria of rats with chronic intoxication. In particular, this was expressed in a reduction in the lag phase, a decrease in the threshold calcium concentration required to open a pore, an acceleration of high-amplitude cyclosporin-sensitive swelling of mitochondria, as well as an increase in the effect of carbenoxolone on the level of mitochondrial membrane-bound proteins. Thus, as a result of the studies carried out, it was shown that carbenoxolone is involved in the development/modulation of alcohol tolerance and dependence in rats.     

Step-by-Step Immune Activation for Suicide Gene Therapy Reinforcement

Gene-directed enzyme prodrug gene therapy (GDEPT) theoretically represents a useful method to carry out chemotherapy for cancer with minimal side effects through the formation of a chemotherapeutic agent inside cancer cells. However, despite great efforts, promising preliminary results, and a long period of time (over 25 years) since the first mention of this method, GDEPT has not yet reached the clinic. There is a growing consensus that optimal cancer therapies should generate robust tumor-specific immune responses. The advent of checkpoint immunotherapy has yielded new highly promising avenues of study in cancer therapy. For such therapy, it seems reasonable to use combinations of different immunomodulators alongside traditional methods, such as chemotherapy and radiotherapy, as well as GDEPT. In this review, we focused on non-viral gene immunotherapy systems combining the intratumoral production of toxins diffused by GDEPT and immunomodulatory molecules. Special attention was paid to the applications and mechanisms of action of the granulocyte-macrophage colony-stimulating factor (GM–CSF), a cytokine that is widely used but shows contradictory effects. Another method to enhance the formation of stable immune responses in a tumor, the use of danger signals, is also discussed. The process of dying from GDEPT cancer cells initiates danger signaling by releasing damage-associated molecular patterns (DAMPs) that exert immature dendritic cells by increasing antigen uptake, maturation, and antigen presentation to cytotoxic T-lymphocytes. We hypothesized that the combined action of this danger signal and GM–CSF issued from the same dying cancer cell within a limited space would focus on a limited pool of immature dendritic cells, thus acting synergistically and enhancing their maturation and cytotoxic T-lymphocyte attraction potential. We also discuss the problem of enhancing the cancer specificity of the combined GDEPT–GM–CSF–danger signal system by means of artificial cancer specific promoters or a modified delivery system.     

Highly potent and specific GSK-3beta inhibitors that block tau phosphorylation and decrease alpha-synuclein protein expression in a cellular model of Parkinson's disease

Research by Klein and co-workers suggests that the inhibition of GSK-3beta by small molecules may offer an important strategy in the treatment of a number of central nervous system (CNS) disorders including Alzheimer's disease, Parkinson's disease, and bipolar disorders. Based on results from kinase-screening assays that identified a staurosporine analogue as a modest inhibitor of GSK-3beta, a series of 3-indolyl-4-indazolylmaleimides was prepared for study in both enzymatic and cell-based assays. Most strikingly, whereas we identified ligands having poor to high potency for GSK-3beta inhibition, only ligands with a Ki value of less than 8 nM, namely maleimides 18 and 22, were found to inhibit Tau phosphorylation at a GSK-3beta-specific site (Ser 396/404). Accordingly, maleimides 18 and 22 may protect neuronal cells against cell death by decreasing the level of alpha-Syn protein expression. We conclude that the GSK-3beta inhibitors described herein offer promise in defending cells against MPP+-induced neurotoxicity and that such compounds will be valuable to explore in animal models of Parkinson's disease as well as in other Tau-related neurodegenerative disease states.     

Evaluation of service life design models on concrete structures exposed to marine environment

Durability of reinforced concrete is primarily influenced by the penetration of aggressive substances into concrete, which are degrading concrete and reinforcement. For structures in marine environment chlorides are the most critical environmental load, which are causing serious corrosion damages. Data collected during the survey of the Krk Bridge, a large reinforced concrete arch bridge structure located on the Adriatic coast, is used as documented reference in this research. The structure has been exposed to the marine environment for over 25 years. Based on collected materials data and the exposure conditions, the service life of this structure is estimated using three currently available prediction models, two deterministic models, the North American Life-365 model and the Croatian CHLODIF model, and the DuraCrete probabilistic method. All these models are based on the chloride diffusion process, but with different detailing of the model parameters. The conclusion is an evaluation of the service life predictive ability of each of these three service life models.     

Fluorographene: a two-dimensional counterpart of Teflon

A stoichiometric derivative of graphene with a fluorine atom attached to each carbon is reported. Raman, optical, structural, micromechanical, and transport studies show that the material is qualitatively different from the known graphene-based nonstoichiometric derivatives. Fluorographene is a high-quality insulator (resistivity >10(12) Ω) with an optical gap of 3 eV. It inherits the mechanical strength of graphene, exhibiting a Young's modulus of 100 N m(-1) and sustaining strains of 15%. Fluorographene is inert and stable up to 400 °C even in air, similar to Teflon.     

Fluorinated graphene: Fluorographene: A Two‐Dimensional Counterpart of Teflon (Small 24/2010)

A stoichiometric derivative of graphene with a fluorine atom attached to each carbon is reported. Raman, optical, structural, micromechanical, and transport studies show that the material is qualitatively different from the known graphene‐based nonstoichiometric derivatives. Fluorographene is a high‐quality insulator (resistivity >10¹² Ω) with an optical gap of 3 eV. It inherits the mechanical strength of graphene, exhibiting a Young’s modulus of 100 N m^?1 and sustaining strains of 15%. Fluorographene is inert and stable up to 400 °C even in air, similar to Teflon.