Nanotechnology and microfluidics:formulation design and on-chip manufacture of nanoparticles

Nanoparticles offer an ideal platform for the delivery of small molecule drugs, subunit vaccines and genetic constructs. Besides the necessity of a homogenous size distribution, defined loading efficiencies and reasonable production and development costs, one of the major bottlenecks in translating nanoparticles into clinical application is the need for rapid, robust and reproducible development techniques. Within this thesis, microfluidic methods were investigated for the manufacturing, drug or protein loading and purification of pharmaceutically relevant nanoparticles. Initially, methods to prepare small liposomes were evaluated and compared to a microfluidics-directed nanoprecipitation method. To support the implementation of statistical process control, design of experiment models aided the process robustness and validation for the methods investigated and gave an initial overview of the size ranges obtainable in each method whilst evaluating advantages and disadvantages of each method. The lab-on-a-chip system resulted in a high-throughput vesicle manufacturing, enabling a rapid process and a high degree of process control. To further investigate this method, cationic low transition temperature lipids, cationic bola-amphiphiles with delocalized charge centers, neutral lipids and polymers were used in the microfluidics-directed nanoprecipitation method to formulate vesicles. Whereas the total flow rate (TFR) and the ratio of solvent to aqueous stream (flow rate ratio, FRR) was shown to be influential for controlling the vesicle size in high transition temperature lipids, the factor FRR was found the most influential factor controlling the size of vesicles consisting of low transition temperature lipids and polymer-based nanoparticles. The biological activity of the resulting constructs was confirmed by an invitro transfection of pDNA constructs using cationic nanoprecipitated vesicles. Design of experiments and multivariate data analysis revealed the mathematical relationship and significance of the factors TFR and FRR in the microfluidics process to the liposome size, polydispersity and transfection efficiency. Multivariate tools were used to cluster and predict specific in-vivo immune responses dependent on key liposome adjuvant characteristics upon delivery a tuberculosis antigen in a vaccine candidate. The addition of a low solubility model drug (propofol) in the nanoprecipitation method resulted in a significantly higher solubilisation of the drug within the liposomal bilayer, compared to the control method. The microfluidics method underwent scale-up work by increasing the channel diameter and parallelisation of the mixers in a planar way, resulting in an overall 40-fold increase in throughput. Furthermore, microfluidic tools were developed based on a microfluidics-directed tangential flow filtration, which allowed for a continuous manufacturing, purification and concentration of liposomal drug products.

Fiscal and Monetary Institutions in Central, Eastern and South-Eastern European Countries

This paper studies the role of fiscal and monetary institutions in macroeconomic stability and budgetary control in central, eastern and south-eastern European countries (CESEE) in comparison with other OECD countries. CESEE countries tend to grow faster and have more volatile output than non-CESEE OECD countries, which has implications for macroeconomic management: better fiscal and monetary institutions are needed to avoid pro-cyclical policies. The paper develops a Budgetary Discipline Index to assess whether good fiscal institutions underpin good fiscal outcomes. Even though most CESEE countries have low scores, the debt/GDP ratios declined before the crisis. This was largely the consequence of a very favourable relationship between the economic growth rate and the interest rate, but such a favourable relationship is not expected in the future. Econometric estimations confirm that better monetary institutions reduce macroeconomic volatility and that countries with better budgetary procedures have better fiscal outcomes. All these factors call for improved monetary institutions, stronger fiscal rules and better budgetary procedures in CESEE countries.

Exchange Rate Policy and Economic Growth after the Financial Crisis in Central and Eastern Europe

In a paper on the effects of the global financial crisis in Central and Eastern Europe (CEE), the author reacts to a paper of Åslund (2011) published in the same issue of Eurasian Geography and Economics on the influence of exchange rate policies on the region’s recovery. The author argues that post-crisis corrections in current account deficits in CEE countries do not in themselves signal a return to steady economic growth. Disagreeing with Åslund over the role of loose monetary policy in fostering the region’s economic problems, he outlines a number of competitiveness problems that remain to be addressed in the 10 new EU member states of CEE, along with improvements in framework conditions supporting future macroeconomic growth.

Tax morale and tax evasion: Social preferences and bounded rationality

We study a family of models of tax evasion, where a flat-rate tax finances only the provision of public goods, neglecting audits and wage differences. We focus on the comparison of two modeling approaches. The first is based on optimizing agents, who are endowed with social preferences, their utility being the sum of private consumption and moral utility. The second approach involves agents acting according to simple heuristics. We find that while we encounter the traditionally shaped Laffer-curve in the optimizing model, the heuristics models exhibit (linearly) increasing Laffercurves. This difference is related to a peculiar type of behavior emerging within the heuristics based approach: a number of agents lurk in a moral state of limbo, alternating between altruism and selfishness.

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.

The Euro Area's Tightrope Walk: Debt and Competitiveness in Italy and Spain

- Competitiveness adjustment in struggling southern euro-area members requires persistently lower inflation than in major trading partners, but low inflation worsens public debt sustainability. When average euro-area inflation undershoots the two percent target, the conflict between intra-euro relative price adjustment and debt sustainability is more severe. - In our baseline scenario, the projected public debt ratio reduction in Italy and Spain is too slow and does not meet the European fiscal rule. Debt projections are very sensitive to underlying assumptions and even small negative deviations from GDP growth, inflation and budget surplus assumptions can easily result in a runaway debt trajectory. - The case for a greater than five percent of GDP primary budget surplus is very weak. Beyond vitally important structural reforms, the top priority is to ensure that euro-area inflation does not undershoot the two percent target, which requires national policy actions and more accommodative monetary policy. The latter would weaken the euro exchange rate, thereby facilitating further intra-euro adjustment. More effective policies are needed to foster growth. But if all else fails, the European Central Bank’s Outright Monetary Transactions could reduce borrowing costs.

A new epistemic model

Meier (2012) gave a "mathematical logic foundation" of the purely measurable universal type space (Heifetz and Samet, 1998). The mathematical logic foundation, however, discloses an inconsistency in the type space literature: a finitary language is used for the belief hierarchies and an infinitary language is used for the beliefs. In this paper we propose an epistemic model to fix the inconsistency above. We show that in this new model the universal knowledgebelief space exists, is complete and encompasses all belief hierarchies. Moreover, by examples we demonstrate that in this model the players can agree to disagree Aumann (1976)'s result does not hold, and Aumann and Brandenburger (1995)'s conditions are not sufficient for Nash equilibrium. However, we show that if we substitute selfevidence (Osborne and Rubinstein, 1994) for common knowledge, then we get at that both Aumann (1976)'s and Aumann and Brandenburger (1995)'s results hold.

Innovációmenedzsment és innovációs stratégiák – a vállalati tudás szerepe az innovációs folyamatokban (Innovation management and innovation strategies – the role of corporate knowledge in innovative processes)

A szerzők kutatásának célja, hogy az innovációmenedzsment és az innovációs stratégiák összefüggéseiben rávilágítsanak a magyarországi vállalatokat jellemző stratégiai irányokra és azonosítsák a vállalati tudás szerepét az innovációs folyamatokban. Az induktív logikán alapuló, kvalitatív interjúkra építkező módszertan segítségével történt az adatok gyűjtése és elemzése. Kutatási eredményeik alapján megállapítható, hogy a magyar vállalatok többsége tisztában van az innováció stratégiai jelentőségével és a tudás innovációfokozó erejével. Azonban a bizonytalan szabályozási környezet, a negatív piaci hangulat, a finanszírozási forrásokhoz való hozzáférés és a globális verseny megnehezítik a hazai KKV-k innovációs törekvéseit. Ugyanakkor a multinacionális vállalatok élen járnak mind a technológiai, mind pedig a nem technológiai innovációk terén is. A nem technológiai innováció területén komoly fejlődési lehetőségek körvonalazódhatnak a magyar KKV-k számára is, hiszen ezek kevésbé költségesek és időigényesek, és a belső erőforrásokat felhasználva a szervezeti tudásbázisra is épülhetnek. ____ The aim of the authors’ research is to highlight the characteristic strategic directions of Hungarian companies and identify the role of corporate knowledge in the innovative processes in the context of innovation management and innovative strategies. The collection and analysis of data were helped by a methodology which is based on inductive logic and qualitative interviews. The diagnosis, based on there search results,was that the majority of Hungarian companies are aware of the strategic importance of innovation and the innovation enhancing power of knowledge.

Effects of using manipulative materials to teach remedial algebra to community college students on achievement and attitudes towards mathematics

This dissertation derived hypotheses from the theories of Piaget, Bruner and Dienes regarding the effects of using Algebra Tiles and other manipulative materials to teach remedial algebra to community college students. The dependent variables measured were achievement and attitude towards mathematics. The Piagetian cognitive level of the students in the study was measured and used as a concomitant factor in the study.^ The population for the study was comprised of remedial algebra students at a large urban community college. The sample for the study consisted of 253 students enrolled in 10 sections of remedial algebra at three of the six campuses of the college. Pretests included administration of an achievement pre-measure, Aiken's Mathematics Attitude Inventory (MAI), and the Group Assessment of Logical Thinking (GALT). Posttest measures included a course final exam and a second administration of the MAI.^ The results of the GALT test revealed that 161 students (63.6%) were concrete operational, 65 (25.7%) were transitional, and 27 (10.7%) were formal operational. For the purpose of analyzing the data, the transitional and formal operational students were grouped together.^ Univariate factorial analyses of covariance ($\alpha$ =.05) were performed on the posttest of achievement (covariate = achievement pretest) and the MAI posttest (covariate = MAI pretest). The factors used in the analysis were method of teaching (manipulative vs. traditional) and cognitive level (concrete operational vs. transitional/formal operational).^ The analyses for achievement revealed a significant difference in favor of the manipulatives groups in the computations by campus. Significant differences were not noted in the analysis by individual instructors.^ The results for attitude towards mathematics showed a significant difference in favor of the manipulatives groups for the college-wide analysis and for one campus. The analysis by individual instructor was not significant. In addition, the college-wide analysis was significant in favor of the transitional/formal operational stage of cognitive development. However, support for this conclusion was not obtained in the analyses by campus or individual instructor. ^

Refinement methods for software architecture design using the software architecture model

Modern software systems are often large and complicated. To better understand, develop, and manage large software systems, researchers have studied software architectures that provide the top level overall structural design of software systems for the last decade. One major research focus on software architectures is formal architecture description languages, but most existing research focuses primarily on the descriptive capability and puts less emphasis on software architecture design methods and formal analysis techniques, which are necessary to develop correct software architecture design. ^ Refinement is a general approach of adding details to a software design. A formal refinement method can further ensure certain design properties. This dissertation proposes refinement methods, including a set of formal refinement patterns and complementary verification techniques, for software architecture design using Software Architecture Model (SAM), which was developed at Florida International University. First, a general guideline for software architecture design in SAM is proposed. Second, specification construction through property-preserving refinement patterns is discussed. The refinement patterns are categorized into connector refinement, component refinement and high-level Petri nets refinement. These three levels of refinement patterns are applicable to overall system interaction, architectural components, and underlying formal language, respectively. Third, verification after modeling as a complementary technique to specification refinement is discussed. Two formal verification tools, the Stanford Temporal Prover (STeP) and the Simple Promela Interpreter (SPIN), are adopted into SAM to develop the initial models. Fourth, formalization and refinement of security issues are studied. A method for security enforcement in SAM is proposed. The Role-Based Access Control model is formalized using predicate transition nets and Z notation. The patterns of enforcing access control and auditing are proposed. Finally, modeling and refining a life insurance system is used to demonstrate how to apply the refinement patterns for software architecture design using SAM and how to integrate the access control model. ^ The results of this dissertation demonstrate that a refinement method is an effective way to develop a high assurance system. The method developed in this dissertation extends existing work on modeling software architectures using SAM and makes SAM a more usable and valuable formal tool for software architecture design. ^

Design optimization of modern machine drive systems for maximum fault tolerant and optimal operation

Modern electric machine drives, particularly three phase permanent magnet machine drive systems represent an indispensable part of high power density products. Such products include; hybrid electric vehicles, large propulsion systems, and automation products. Reliability and cost of these products are directly related to the reliability and cost of these systems. The compatibility of the electric machine and its drive system for optimal cost and operation has been a large challenge in industrial applications. The main objective of this dissertation is to find a design and control scheme for the best compromise between the reliability and optimality of the electric machine-drive system. The effort presented here is motivated by the need to find new techniques to connect the design and control of electric machines and drive systems. ^ A highly accurate and computationally efficient modeling process was developed to monitor the magnetic, thermal, and electrical aspects of the electric machine in its operational environments. The modeling process was also utilized in the design process in form finite element based optimization process. It was also used in hardware in the loop finite element based optimization process. The modeling process was later employed in the design of a very accurate and highly efficient physics-based customized observers that are required for the fault diagnosis as well the sensorless rotor position estimation. Two test setups with different ratings and topologies were numerically and experimentally tested to verify the effectiveness of the proposed techniques. ^ The modeling process was also employed in the real-time demagnetization control of the machine. Various real-time scenarios were successfully verified. It was shown that this process gives the potential to optimally redefine the assumptions in sizing the permanent magnets of the machine and DC bus voltage of the drive for the worst operating conditions. ^ The mathematical development and stability criteria of the physics-based modeling of the machine, design optimization, and the physics-based fault diagnosis and the physics-based sensorless technique are described in detail. ^ To investigate the performance of the developed design test-bed, software and hardware setups were constructed first. Several topologies of the permanent magnet machine were optimized inside the optimization test-bed. To investigate the performance of the developed sensorless control, a test-bed including a 0.25 (kW) surface mounted permanent magnet synchronous machine example was created. The verification of the proposed technique in a range from medium to very low speed, effectively show the intelligent design capability of the proposed system. Additionally, to investigate the performance of the developed fault diagnosis system, a test-bed including a 0.8 (kW) surface mounted permanent magnet synchronous machine example with trapezoidal back electromotive force was created. The results verify the use of the proposed technique under dynamic eccentricity, DC bus voltage variations, and harmonic loading condition make the system an ideal case for propulsion systems.^

Analysis of Students’ Misconceptions and Error Patterns in Mathematics: The Case of Fractions

This study analyzed three fifth grade students’ misconceptions and error patterns when working with equivalence, addition and subtraction of fractions. The findings revealed that students used both conceptual and procedural knowledge to solve the problems. They used pictures, gave examples, and made connections to other mathematical concepts and to daily life topics. Error patterns found include using addition and subtraction of numerators and denominators, and finding the greatest common factor.

Relationship between a middle school band director's attire and incidences of student off-task behaviors in the classroom

The purpose of this study was to examine whether a middle school band director's attire had an effect on off-task student behaviors in his classroom. One male middle school band director participated and three of his classes were observed. The study lasted twenty days and consisted of three treatments (casual attire, business casual attire, and formal business attire). A tally sheet was used to determine the number of off-task behaviors per student per minute. The results indicated that in this classroom, the students (of all three classes) were off-task less often when the band director wore business casual attire. This was the clothing that he wore consistently from the beginning of the school year. Straying from this consistency made off-task behaviors in the classroom rise. The most off-task behaviors occurred when the band director wore casual clothing. Off-task behaviors also rose when the band director wore business formal attire.

Certificação de composições de serviços web semânticos

This thesis presents a certification method for semantic web services compositions which aims to statically ensure its functional correctness. Certification method encompasses two dimensions of verification, termed base and functional dimensions. Base dimension concerns with the verification of application correctness of the semantic web service in the composition, i.e., to ensure that each service invocation given in the composition comply with its respective service definition. The certification of this dimension exploits the semantic compatibility between the invocation arguments and formal parameters of the semantic web service. Functional dimension aims to ensure that the composition satisfies a given specification expressed in the form of preconditions and postconditions. This dimension is formalized by a Hoare logic based calculus. Partial correctness specifications involving compositions of semantic web services can be derived from the deductive system proposed. Our work is also characterized by exploiting the use of a fragment of description logic, i.e., ALC, to express the partial correctness specifications. In order to operationalize the proposed certification method, we developed a supporting environment for defining the semantic web services compositions as well as to conduct the certification process. The certification method were experimentally evaluated by applying it in three different proof concepts. These proof concepts enabled to broadly evaluate the method certification

Lacan, Gödel, a ciência e a verdade

Jaques Lacan, the thinker who proposes a return to the fundamentals of psychoanalysis in Freud states that the math would face as a privileged way of transmission of knowledge by the science. Although he was a follower of the mathematization of nature as the foundation of modern science, for him this principle does not imply eliminating the subject that produces it. That would be equivalent to saying that there can not be a language, whatever, even the math, that may "erases" the subject assumption in science. In the text The science and the truth we will try to introduce the idea, not so simple, by the way, the truth as the cause. Citing the framework of the causes in Aristotle, Lacan will speak of a homology between the truth as formal cause, in the case of science, and the truth as material cause, on the side of psychoanalysis. Among its aims with this text, he wants to establish that the unconscious of the subject would be none other than the subject of science. The famous incompleteness theorems of logical-mathematical Kurt Gödel enter here as a chapter of this issue. Recognized as true watershed, these theorems have to be remembered as revealing even outside the mathematical environment, and Lacan himself is not indifferent to this. He makes mention of Gödel's name and draws some observations apparently modest support for his own theory. Since some technical sophisticated knowledges awaits the reader who intends understand this supposed corroboration that Gödel provides to psychoanalysis, introduce the student of Lacan in the use he makes of the incompleteness theorems is the objective of this work. In The science and the truth, which fits us to locate the name of Gödel, one must question how seize such an idea without incurring the extrapolation and abuse of mathematical knowledge, almost trivial in this case. Thus, this paper aims to introduce the reader to the reasoning behind the theorems of Gödel, acquaint him about the Lacan’s mathematical claims, and indicate how to proceed using this implicit math in the text The science and the truth.