Szebeni J.,University of Miskolc |
Muggia F.,New York University |
Gabizon A.,Hebrew University of Jerusalem |
Barenholz Y.,Hebrew University of Jerusalem
Advanced Drug Delivery Reviews | Year: 2011
Some therapeutic liposomes and lipid excipient-based anticancer drugs are recognized by the immune system as foreign, leading to a variety of adverse immune phenomena. One of them is complement (C) activation, the cause, or major contributing factor to a hypersensitivity syndrome called C activation-related pseudoallergy (CARPA). CARPA represents a novel subcategory of acute (type I) hypersensitivity reactions (HSR), which is mostly mild, transient, and preventable by appropriate precautions. However, in an occasional patient, it can be severe or even lethal. Because a main manifestation of C activation is cardiopulmonary distress, CARPA may be a safety issue primarily in cardiac patients. Along with an overview of the various types of liposome-immune system interactions, this review updates the experimental and clinical information on CARPA to different therapeutic liposomes and lipid excipient-based (micellar) anticancer drugs, including PEGylated liposomal doxorubicin sulfate (PLD, Doxil ®) and paclitaxel (Taxol ®). The substantial individual variation of in vitro and in vivo findings reflects an extremely complex immune phenomenon involving multiple, redundant pathways of C activation, signal transduction in allergy-mediating cells and vasoactive mediator actions at the effector cell level. The latest advances in this field include the proposal of doxorubicin-induced shape changes and aggregation of liposomes in Doxil as possible contributing factors to CARPA caused by PLD, and the finding that Doxil-induced immune suppression prevents HSR to co-administered carboplatin, a significant benefit of Doxil in combination chemotherapy with carboplatin. The review evaluates the use of in vitro C assays and the porcine liposome-induced cardiopulmonary distress model for predicting CARPA. It is concluded that CARPA may become a frequent safety issue in the upcoming era of nanomedicines, necessitating its prevention at an early stage of nanomedicine R&D. © 2011.
Vincze D.,University of Miskolc
SAMI 2017 - IEEE 15th International Symposium on Applied Machine Intelligence and Informatics, Proceedings | Year: 2017
Reinforcement Learning (RL) methods became popular decades ago and still maintain to be one of the mainstream topics in computational intelligence. Countless different RL methods and variants can be found in the literature, each one having its own advantages and disadvantages in a specific application domain. Representation of the revealed knowledge can be realized in several ways depending on the exact RL method, including e.g. simple discrete Q-tables, fuzzy rule-bases, artificial neural networks. Introducing interpolation within the knowledge-base allows the omission of less important, redundant information, while still keeping the system functional. A Fuzzy Rule Interpolation-based (FRI) RL method called FRIQ-learning is a method which possesses this feature. By omitting the unimportant, dependent fuzzy rules - emphasizing the cardinal entries of the knowledge representation - FRIQ-learning is also suitable for knowledge extraction. In this paper the fundamental concepts of FRIQ-learning and associated extensions of the method along with benchmarks will be discussed. © 2017 IEEE.
Kaptay G.,University of Miskolc
International Journal of Pharmaceutics | Year: 2012
The general equation is derived for the equilibrium of a small solid particle and a large solution, being consistent with the thermodynamics of Gibbs. This equation can be solved in a closed form for solubility if an ideal (or an infinitely diluted) solution is considered, if the interfacial energy is independent of the composition of the solution and if all physical parameters (other than the solubility itself) are taken size independent. The solubility of the particles is found to increase with increasing its specific surface area, i.e. if non-spherical particles are applied. This simplified solution further simplifies if the shape of the solid is supposed to be spherical. This latter equation, however, is found to be in contradiction with the Ostwald-Freundlich equation, widely used in chemistry, biology and materials science to describe the size dependence of solubility of a spherical crystal. The reason for its incorrectness is shown to be due to the incorrect application of the Laplace equation. It is found that the solubility increases with decreasing the size of the dissolving phase not due to the increased curvature of the phase (Kelvin and Freundlich), but rather due to the increased specific surface area of the phase (Gibss, Ostwald). Equations are also derived for the case, when the size effect of the interfacial energy is taken into account, and when the crystal is surrounded by several planes of different interfacial energies. The role of wettability is discussed on the size dependence of solubility. © 2012 Elsevier B.V. All rights reserved.
Varga G.,University of Miskolc
Key Engineering Materials | Year: 2014
In this study we analysed the process of diamond burnishing. We examined the effect of burnishing technological parameters on the surface roughness of the burnished surface, and on the improvement ratio of surface roughness. Parameters taken into consideration during examinations are burnishing speed, burnishing feed, and burnishing force. We determined a formula suitable for determination of the improvement ratio of surface roughness by the factorial experimental design which is valid in the examined parameter range. © (2014) Trans Tech Publications, Switzerland.
Gregory J.,University College London |
Barany S.,University of Miskolc
Advances in Colloid and Interface Science | Year: 2011
Polymers of various types are in widespread use as flocculants in several industries. In most cases, polymer adsorption is an essential prerequisite for flocculation and kinetic aspects are very important. The rates of polymer adsorption and of re-conformation (relaxation) of adsorbed chains are key factors that influence the performance of flocculants and their mode of action. Polyelectrolytes often tend to adopt a rather flat adsorbed configuration and in this state their action is mainly through charge effects, including 'electrostatic patch' attraction. When the relaxation rate is quite low, particle collisions may occur while the adsorbed chains are still in an extended state and flocculation by polymer bridging may occur. These effects are now well understood and supported by much experimental evidence. In recent years there has been considerable interest in the use of multi-component flocculants, especially dual-polymer systems. In the latter case, there can be significant advantages over the use of single polymers. Despite some complications, there is a broad understanding of the action of dual polymer systems. In many cases the sequence of addition of the polymers is important and the pre-adsorbed polymer can have two important effects: providing adsorption sites for the second polymer or causing a more extended adsorbed conformation as a result of 'site blocking'. © 2011 Elsevier B.V. All rights reserved.
Lukacs A.,University of Miskolc
Pediatric diabetes | Year: 2012
To evaluate motor performance and cardiorespiratory function in youths with type 1 diabetes in comparison with age-matched control groups and to analyze the influence of physical activity level, anthropometric and physical fitness parameters on long-term metabolic control. 106 youths with diabetes and 130 healthy youths aged 8-18 were assessed by the Eurofit test regarding motor performances, cardiorespiratory fitness (VO2max), skinfold thickness, and body mass index. Physical activity level was assessed through the use of questionnaires. Predictors of physical fitness and metabolic control were determined with regression analysis. There were no differences either in body composition or in physical activity level, but younger girls with diabetes had impaired results in speed of upper limb movement, abdominal muscle strength, upper body strength, running speed, and VO2max ; older girls with diabetes had poor results in speed of upper limb movement, abdominal muscle strength, upper body strength and VO2max . Younger boys with diabetes had impaired results in speed of upper limb movement, flexibility, static strength of hand, and abdominal muscle strength; and older boys with diabetes had poor results in speed of upper limb movement, flexibility, abdominal muscle strength, upper body strength, and VO2max compared with control groups. Older age, female gender, lower physical activity level, and higher HbA1c were significant independent predictors of poorer VO2max. Better VO2max proved to be the single predictor of favorable HbA1c . Youths with diabetes have reduced fitness parameters. Efforts should be carried out to improve physical fitness as part of treatment and care of children and adolescents with type 1 diabetes. © 2012 John Wiley & Sons A/S.
Szebeni J.,University of Miskolc
Molecular Immunology | Year: 2014
Intravenous injection of a variety of nanotechnology enhanced (liposomal, micellar, polymer-conjugated) and protein-based (antibodies, enzymes) drugs can lead to hypersensitivity reactions (HSRs), also known as infusion, or anaphylactoid reactions. The molecular mechanism of mild to severe allergy symptoms may differ from case to case and is mostly not known, however, in many cases a major cause, or contributing factor is activation of the complement (C) system. The clinical relevance of C activation-related HSRs, a non-IgE-mediated pseudoallergy (CARPA), lies in its unpredictability and occasional lethal outcome. Accordingly, there is an unmet medical need to develop laboratory assays and animal models that quantitate CARPA. This review provides basic information on CARPA; a short history, issues of nomenclature, incidence, classification of reactogenic drugs and symptoms, and the mechanisms of C activation via different pathways. It is pointed out that anaphylatoxin-induced mast cell release may not entirely explain the severe reactions; a "second hit" on allergy mediating cells may also contribute. In addressing the increasing requirements for CARPA testing, the review evaluates the available assays and animal models, and proposes a possible algorithm for the screening of reactogenic drugs and hypersensitive patients. Finally, an analogy is proposed between CARPA and the classic stress reaction, suggesting that CARPA represents a "blood stress" reaction, a systemic fight of the body against harmful biological and chemical agents via the anaphylatoxin/mast-cell/circulatory system axis, in analogy to the body's fight of physical and emotional stress via the hypothalamo/pituitary/adrenal axis. In both cases the response to a broad variety of noxious effects are funneled into a uniform pattern of physiological changes. © 2014 Elsevier Ltd.
Palmai Z.,University of Miskolc
Wear | Year: 2013
Based on studies of the physical characteristics of wear processes, the conclusion could be drawn that the cutting distance must be considered not only in abrasive and adhesive processes but also in thermally-activated diffusion and oxidation processes. Consequently, it can be proposed that a mathematical model of the rate of flank wear-an autonomous non-linear differential equation that takes into account the wear-accelerating effect of both the technological parameters of cutting and the temperature developing on the tool flank-can be applied. Furthermore, this model may be used to calculate the tool life and the Taylor formula related to any arbitrarily chosen failure criteria. Technological parameters may also change periodically or continuously depending on time. The constants of the wear equation and the apparent activation energy of the process can be determined by cutting experiments and also by measurements of wear performed during factory manufacturing under a variety of technological parameters. The complex wear equation was validated by the cutting tests performed with P20 carbide on AISI1045 carbon steel. The adverse effect of rapidly changing cutting speed on the wear of the tool during vibration could be modelled. A new theoretical model of the cutting tool's flank wear rate. The mathematical model is an autonomous non-linear differential equation. Technological parameters may also change depending on time. The measurement of wear performed during factory manufacturing. The wear equation was validated with P20 carbide on AISI1045 carbon steel. © 2013 Elsevier B.V.
Ecsedi I.,University of Miskolc
Mechanics Research Communications | Year: 2013
The Saint-Venant torsion of linearly elastic anisotropic cylindrical bars with solid and hollow cross-section is treated. The shear flexibility moduli of the non-homogeneous bar are given functions of the Prandtl's stress function of considered cylindrical bar when its material is homogeneous. The solution of the torsion problem of non-homogeneous anisotropic bar is expressed in terms of the torsion and Prandtl's stress functions of the corresponding homogeneous anisotropic bar having the same cross-section as the non-homogeneous bar. © 2013 Elsevier Ltd.
Kaptay G.,University of Miskolc
Metallurgical and Materials Transactions A: Physical Metallurgy and Materials Science | Year: 2012
The rule of Lupis and Elliott (LE rule) proposed for the first time in 1966 is reformulated in this article as, "Real solid, liquid and gaseous solutions (and pure gases) gradually approach the state of an ideal solution (perfect gas) as temperature increases at any fixed pressure and composition." This rule is rationalized through the heat expansion of phases and loss of any interaction with increased separation between the atoms. It is shown that the rule is valid only if the standard state is selected properly, i.e., if mixing does not involve any hidden phase changes, such as melting. It is shown that the necessary and sufficient practical conditions to obey the LE rule is the equality of signs of the heat of mixing and excess entropy of mixing and the nonequality of signs of heat of mixing and excess heat capacity of mixing of the same solution. It is shown that these two conditions are fulfilled for most of the experimentally measured high-temperature solutions. The LE rule is compared with the existing laws of thermodynamics. It is shown that the LE rule can be considered as a potential fourth law of materials thermodynamics. © The Minerals, Metals & Materials Society and ASM International 2011.