Development of plasmid dna formulations for application as microspheric dna vaccines

The advent of DNA vaccines has heralded a new technology allowing the design and elicitation of immune responses more adequate for a wider range of pathogens. The formulation of these vaccines into the desired dosage forms extends their capability in terms of stability, routes of administration and efficacy. This thesis describes an investigation into the fabrication of plasmid DNA, the active principle of DNA vaccines, into microspheres, based on the tenet of an increased cellular uptake of microparticulate matter by phagocytic cells. The formulation of plasmid DNA into microspheres using two methods, is presented. Formulation of microspheric plasmid DNA using the double emulsion solvent evaporation method and a spray-drying method was explored. The former approach involves formation of a double emulsion, by homogenisation. This method produced microspheres of uniform size and smooth morphology, but had a detrimental effect on the formulated DNA. The spray-drying method resulted in microspheres with an improved preservation of DNA stability. The use of polyethylenimine (PEI) and stearylamine (SA) as agents in the microspheric formulation of plasmid DNA is a novel approach to DNA vaccine design. Using these molecules as model positively-charged agents, their influence on the characteristics of the microspheric formulations was investigated. PEI improved the entrapment efficiency of the plasmid DNA in microspheres, and has minimal effect on either the surface charge, morphology or size distribution of the formulations. Stearylamine effected an increase in the entrapment efficiency and stability of the plasmid DNA and its effect on the micropshere morphology was dependent on the method of preparation. The differences in the effects of the two molecules on microsphere formulations may be attributable to their dissimilar physico-chemical properties. PEI is water-soluble and highly-branched, while SA is hydrophobic and amphipathic. The positive charge of both molecules is imparted by amine functional groups. Preliminary data on the in vivo application of formulated DNA vaccine, using hepatitis B plasmid, showed superior humoral responses to the formulated antigen, compared with free (unformulated) antigen.

The Mechanics of the drawing of polygonal sections from round at elevated temperature

Economic factors such as the rise in cost of raw materials, labour and power, are compelling manufacturers of cold-drawn polygonal sections, to seek new production routes which will enable the expansion in the varieties of metals used and the inclusion of difficult-to-draw materials. One such method generating considerable industrial interest is the drawing of polygonal sections from round at elevated temperature. The technique of drawing mild steel, medium carbon steel and boron steel wire into octagonal, hexagonal and square sections from round at up to 850 deg C and 50% reduction of area in one pass has been established. The main objective was to provide a basic understanding of the process, with particular emphasis being placed on modelling using both experimental and theoretical considerations. Elevated temperature stress-strain data was obtained using a modified torsion testing machine. Data were used in the upper bound solution derived and solved numerically to predict drawing stress strain, strain-rate, temperature and flow stress distribution in the deforming zone for a range of variables. The success of this warm working process will, of course, depend on the use of a satisfactory elevated temperature lubricant, an efficient cooling system, a suitable tool material having good wear and thermal shock resistance and an efficient die profile design which incorporates the principle of least work. The merits and demerits of die materials such as tungsten carbide, chromium carbide, Syalon and Stellite are discussed, principally from the standpoint of minimising drawing force and die wear. Generally, the experimental and theoretical results were in good agreement, the drawing stress could be predicted within close limits and the process proved to be technically feasible. Finite element analysis has been carried out on the various die geometries and die materials, to gain a greater understanding of the behaviour of these dies under the process of elevated temperature drawing, and to establish the temperature distribution and thermal distortion in the deforming zone, thus establishing the optimum die design and die material for the process. It is now possible to predict, for the materials already tested, (i) the optimum drawing temperature range, (ii) the maximum possible reduction of area per pass, (iii) the optimum drawing die profiles and die materials, (iv) the most efficient lubricant in terms of reducing the drawing force and die wear.

Fatigue of commercial aluminium alloys

Fatigue crack propagation has been observed for a number of commercial aluminium alloys. Comparable data was obtained for a variety of crack and specimen geometries over a range of crack lengths for a given alloy. Where crack propagation only was of interest the initiation event has been excluded by pre-cracking the specimen using a fin of material adjacent to the crack face. By this method a controlled defect size is introduced in to the specimen. By modification of the D.C. potential drop method it has been shown possible to measure the growth of cracking from 0.12mm by this method. Crack growth from defects greater than 0.6mm have been shown to give conventional crack propagation deduced by principle of similitude. Fatigue fracture surface analysis has been conducted for cracking from both free surfaces and from blunt notches. A `quasi cleavage' feature has been identified and is shown to be prominent when the fatigue stress intensity range is below 10 MNm-3/2.

Application of space-charge electrostatic precipitator for collection of oil mist from pyrolysis gases

A novel electrostatic precipitator CAROLA® is developed for collection of fine oil mists. It operates on the principle of unipolar particle charging in the corona discharge and particle precipitation under the field of space charge. The pilot precipitator was tested at different gas temperatures. It is shown that the increase of gas temperature changes the characteristics of the corona discharge and particle size distribution, especially for droplets sub-micron droplets. The CAROLA® precipitator was used for collection of oil mist from pyrolysis gases at the HALOCLEAN® plant. The flow rate of biomass in the HALOCLEAN® plant was 15-30 kg/h. The particle mass concentration in the raw gas was over 100 g/Nm. The operation voltage of the precipitator was 10-12 kV and corona current up to 0,1 mA. Single stage electrostatic precipitator ensured mass collection efficiency 97-99,5% for pyrolysis oil mist.

A study of the properties and applications of electrostatic charged particle oscillators

This investigation originated from work by Dr. A.H. McIlraith of the National Physical Laboratory who, in 1966, described a new type of charged particle oscillator. This makes use of two equal cylindrical electrodes to constrain the particles in such a way that they follow extremely long oscillatory paths between the electrodes under the influence of an electrostatic field alone. The object of this work has been to study the principle of the oscillator in detail and to investigate its properties and applications. Any device which is capable of creating long electron trajectories has potential application in the field of ultra high vacuum technology. It was therefore considered that a critical review of the problems associated with the production and measurement of ultra high vacuum was relevant in the initial stages of the work. The oscillator has been applied with a considerable degree of success as a high energy electrostatic ion source. This offers several advantages over existing ion sources. It can be operated at much lower pressures without the need of a magnetic field. The oscillator principle has also been applied as a thermionic ionization gauge and has been compared with other ionization gauges to pressures as low as 5 x 10- 11 torr.. This new gauge exhibited a number of advantages over most of the existing gauges. Finally the oscillator has been used in an evaporation ion pump and has exhibited fairly high pumping speeds for argon gas relative to those for nitrogen. This investigation supports the original work of Dr. A.H. McIlraith and shows that his proposed oscillator has considerable potential in the fields of vacuum technology and electron physics.

Undermining patient and public engagement and limiting its impact:the consequences of the Health and Social Care Act 2012 on collective patient and public involvement

Patient and public involvement has been at the heart of UK health policy for more than two decades. This commitment to putting patients at the heart of the British National Health Service (NHS) has become a central principle helping to ensure equity, patient safety and effectiveness in the health system. The recent Health and Social Care Act 2012 is the most significant reform of the NHS since its foundation in 1948. More radically, this legislation undermines the principle of patient and public involvement, public accountability and returns the power for prioritisation of health services to an unaccountable medical elite. This legislation marks a sea-change in the approach to patient and public involvement in the UK and signals a shift in the commitment of the UK government to patient-centred care. © 2013 John Wiley & Sons Ltd.

Automatic Translation of MSC Diagrams into Petri Nets

Development-engineers use in their work languages intended for software or hardware systems design, and test engineers utilize languages effective in verification, analysis of the systems properties and testing. Automatic interfaces between languages of these kinds are necessary in order to avoid ambiguous understanding of specification of models of the systems and inconsistencies in the initial requirements for the systems development. Algorithm of automatic translation of MSC (Message Sequence Chart) diagrams compliant with MSC’2000 standard into Petri Nets is suggested in this paper. Each input MSC diagram is translated into Petri Net (PN), obtained PNs are sequentially composed in order to synthesize a whole system in one final combined PN. The principle of such composition is defined through the basic element of MSC language — conditions. While translating reference table is developed for maintenance of consistent coordination between the input system’s descriptions in MSC language and in PN format. This table is necessary to present the results of analysis and verification on PN in suitable for the development-engineer format of MSC diagrams. The proof of algorithm correctness is based on the use of process algebra ACP. The most significant feature of the given algorithm is the way of handling of conditions. The direction for future work is the development of integral, partially or completely automated technological process, which will allow designing system, testing and verifying its various properties in the one frame.

Hamilton’s Principle with Variable Order Fractional Derivatives

MSC 2010: 26A33, 70H25, 46F12, 34K37 Dedicated to 80-th birthday of Prof. Rudolf Gorenflo

A Taxonomy of Big Data for Optimal Predictive Machine Learning and Data Mining

Big data comes in various ways, types, shapes, forms and sizes. Indeed, almost all areas of science, technology, medicine, public health, economics, business, linguistics and social science are bombarded by ever increasing flows of data begging to be analyzed efficiently and effectively. In this paper, we propose a rough idea of a possible taxonomy of big data, along with some of the most commonly used tools for handling each particular category of bigness. The dimensionality p of the input space and the sample size n are usually the main ingredients in the characterization of data bigness. The specific statistical machine learning technique used to handle a particular big data set will depend on which category it falls in within the bigness taxonomy. Large p small n data sets for instance require a different set of tools from the large n small p variety. Among other tools, we discuss Preprocessing, Standardization, Imputation, Projection, Regularization, Penalization, Compression, Reduction, Selection, Kernelization, Hybridization, Parallelization, Aggregation, Randomization, Replication, Sequentialization. Indeed, it is important to emphasize right away that the so-called no free lunch theorem applies here, in the sense that there is no universally superior method that outperforms all other methods on all categories of bigness. It is also important to stress the fact that simplicity in the sense of Ockham’s razor non-plurality principle of parsimony tends to reign supreme when it comes to massive data. We conclude with a comparison of the predictive performance of some of the most commonly used methods on a few data sets.

On the Recursive Estimation of the Location and of the Size of the Mode of a Probability Density

2000 Mathematics Subject Classification: 62G07, 62L20.

Simulation and experimental analysis of a brushless electrically excited synchronous machine with a hybrid rotor

Electrically excited synchronous machines with brushes and slip rings are popular but hardly used in inflammable and explosive environments. This paper proposes a new brushless electrically excited synchronous motor with a hybrid rotor. It eliminates the use of brushes and slip rings so as to improve the reliability and cost-effectiveness of the traction drive. The proposed motor is characterized with two sets of stator windings with two different pole numbers to provide excitation and drive torque independently. This paper introduces the structure and operating principle of the machine, followed by the analysis of the air-gap magnetic field using the finite-element method. The influence of the excitation winding's pole number on the coupling capability is studied and the operating characteristics of the machine are simulated. These are further examined by the experimental tests on a 16 kW prototype motor. The machine is proved to have good static and dynamic performance, which meets the stringent requirements for traction applications.

A származtatott termékek árazása és annak problémái az egyensúlyelmélet szempontjából (Pricing of derived products and problems with it in terms of equilibrium theory)

A szerző röviden összefoglalja a származtatott termékek árazásával kapcsolatos legfontosabb ismereteket és problémákat. A derivatív árazás elmélete a piacon levő termékek közötti redundanciát kihasználva próbálja meghatározni az egyes termékek relatív árát. Ezt azonban csak teljes piacon lehet megtenni, és így csak teljes piac esetén lehetséges a hasznossági függvények fogalmát az elméletből és a ráépülő gyakorlatból elhagyni, ezért a kockázatsemleges árazás elve félrevezető. Másképpen fogalmazva: a származtatott termékek elmélete csak azon az áron képes a hasznossági függvény fogalmától megszabadulni, ha a piac szerkezetére a valóságban nem teljesülő megkötéseket tesz. Ennek hangsúlyozása mind a piaci gyakorlatban, mind az oktatásban elengedhetetlen. / === / The author sums up briefly the main aspects and problems to do with the pricing of derived products. The theory of derivative pricing uses the redundancy among products on the market to arrive at relative product prices. But this can be done only on a complete market, so that only with a complete market does it become possible to omit from the theory and the practice built upon it the concept of utility functions, and for that reason the principle of risk-neutral pricing is misleading. To put it another way, the theory of derived products is capable of freeing itself from the concept of utility functions only at a price where in practice it places impossible restrictions on the market structure. This it is essential to emphasize in market practice and in teaching.

Seasonal dynamic pattern analysis in service of climate change research. A methodical case-study - monitoring and simulation based on an aquatic insect community

Our aim was to approach an important and well-investigable phenomenon – connected to a relatively simple but real field situation – in such a way, that the results of field observations could be directly comparable with the predictions of a simulation model-system which uses a simple mathematical apparatus and to simultaneously gain such a hypothesis-system, which creates the theoretical opportunity for a later experimental series of studies. As a phenomenon of the study, we chose the seasonal coenological changes of aquatic and semiaquatic Heteroptera community. Based on the observed data, we developed such an ecological model-system, which is suitable for generating realistic patterns highly resembling to the observed temporal patterns, and by the help of which predictions can be given to alternative situations of climatic circumstances not experienced before (e.g. climate changes), and furthermore; which can simulate experimental circumstances. The stable coenological state-plane, which was constructed based on the principle of indirect ordination is suitable for unified handling of data series of monitoring and simulation, and also fits for their comparison. On the state-plane, such deviations of empirical and model-generated data can be observed and analysed, which could otherwise remain hidden.

A interpretação constitucional dos princípios da afetividade e solidariedade familiar pelos tribunais superiores brasileiros

The Brazilian juridical ordain has suffered several transformations on Family Law as of the 1988 Federal Constitution, which incorporated the changes in socio-cultural values and behaviors that appeared in the post-modern Brazilian society, with the repersonalization of the family, beginning with the principles of human dignity, affectivity and familiar solidarity; occurring an enlargement of the concept of family, increasing the relevance of socioaffectivity and eudaimonia. The general purpose of this dissertation is to analyze the constitutional interpretations of paradigmatic cases of the Brazilian Superior Courts checking the conditions and behaviors required to achieve the principles of affectivity and familiar solidarity. To do so, uses an exploratory and descriptive research trough books, scientific papers, jurisprudence, monographs and consult to specialized magazines to identify the reasons and specific purposes of the principles of affectivity and family solidarity within the constitutional norms, systematizing the primary meaning of these principles, then to observe the trial of patriotic courts, the criteria and standards of behavior used in their application. The analysis of recent decisions of the Supreme Federal Court and the Superior Court of Justice on the topic of the familiar relations, utilizing the new interpretative approach to the law that considers man as an ontological being of language, demonstrate that the affectivity and familiar solidarity are constitutional principles concretized in decisions, that don’t affect the principle of protection of the juridical security, that is, don’t cause uncertainty despite the incipient specification of criteria to its use

Do amanhecer ao crepúsculo: o ambiente inteiro por minhas narrativas

The matrix of this dissertation research permeates the design of complex environmental education. Its purpose is the realistic utopia of sustainability focused on the elucidation of a cultural model, a way of life that can guarantee the preservation of the living and non-living wight, to compose a world in which all coexist in harmony. To do so, thinking that model permeates the understanding that we are nature. This understanding can be evidenced both in Karl Marx in his book, the Economic and Philosophical Manuscripts says: "Nature is the essential body of the human being", and Joël de Rosnay, in his book The Symbiotic Man explains that we humans, "are the neurons of the earth." In this same perspective, Elisabet Sahtouris, in his book The Dance of the Earth, has pointed out how little is accurate to say that "there is life on Earth," because we are knowledgeable that our planet is a living organism, then there is the "life of the Earth ". Thus, we are part of this life, we are a part of the whole. With long experience in the environmental field, I seek the collective understanding that environmental education is a process belonging to all areas of knowledge, while margins for its subdivision occasion that begins the role of librarian I am, as a mediator of educational, cultural process, and disseminate information, is an environmental educator. Research conducted lead me to propose a revision of values and attitudes, from a certain reorganization of thought, an ecology of ideas and action, evidenced by readings of education and complexity, especially tuned to the writings of Edgar Morin. This thesis makes use of metaphor as a cognitive operator to emphasize the solar cycle, linking it to the development stages of this work. In summary, we have as a goal to emphasize the importance of the human condition, respect for nature and the principle of natural, cultural and social interdependence. In order for us to have a society that values relationships of solidarity with each other, respect and gratitude for living beings and Mother Earth. What leads me to converge, the reframing of the environment, understanding it as Integer Environment