Stochastic control strategies and adaptive critic methods

Adaptive critic methods have common roots as generalizations of dynamic programming for neural reinforcement learning approaches. Since they approximate the dynamic programming solutions, they are potentially suitable for learning in noisy, nonlinear and nonstationary environments. In this study, a novel probabilistic dual heuristic programming (DHP) based adaptive critic controller is proposed. Distinct to current approaches, the proposed probabilistic (DHP) adaptive critic method takes uncertainties of forward model and inverse controller into consideration. Therefore, it is suitable for deterministic and stochastic control problems characterized by functional uncertainty. Theoretical development of the proposed method is validated by analytically evaluating the correct value of the cost function which satisfies the Bellman equation in a linear quadratic control problem. The target value of the critic network is then calculated and shown to be equal to the analytically derived correct value.

Sensor and software use for the glycaemic management of insulin-treated type 1 and type 2 diabetes patients

Lowering glucose levels, while avoiding hypoglycaemia, can be challenging in insulin-treated patients with diabetes. We evaluated the role of ambulatory glucose profile in optimising glycaemic control in this population. Insulin-treated patients with type 1 and type 2 diabetes were recruited into a prospective, multicentre, 100-day study and randomised to control (n = 28) or intervention (n = 59) groups. The intervention group used ambulatory glucose profile, generated by continuous glucose monitoring, to assess daily glucose levels, whereas the controls relied on capillary glucose testing. Patients were reviewed at days 30 and 45 by the health care professional to adjust insulin therapy. Comparing first and last 2 weeks of the study, ambulatory glucose profile-monitored type 2 diabetes patients (n = 28) showed increased time in euglycaemia (mean ± standard deviation) by 1.4 ± 3.5 h/day (p = 0.0427) associated with reduction in HbA1c from 77 ± 15 to 67 ± 13 mmol/mol (p = 0.0002) without increased hypoglycaemia. Type 1 diabetes patients (n = 25) showed reduction in hypoglycaemia from 1.4 ± 1.7 to 0.8 ± 0.8 h/day (p = 0.0472) associated with a marginal HbA1c decrease from 75 ± 10 to 72 ± 8 mmol/mol (p = 0.0508). Largely similar findings were observed comparing intervention and control groups at end of study. In conclusion, ambulatory glucose profile helps glycaemic management in insulin-treated diabetes patients by increasing time spent in euglycaemia and decreasing HbA1c in type 2 diabetes patients, while reducing hypoglycaemia in type 1 diabetes patients.

Bioactive sol-gel glasses at the atomic scale:the complementary use of advanced probe and computer modeling methods

Sol-gel-synthesized bioactive glasses may be formed via a hydrolysis condensation reaction, silica being introduced in the form of tetraethyl orthosilicate (TEOS), and calcium is typically added in the form of calcium nitrate. The synthesis reaction proceeds in an aqueous environment; the resultant gel is dried, before stabilization by heat treatment. These materials, being amorphous, are complex at the level of their atomic-scale structure, but their bulk properties may only be properly understood on the basis of that structural insight. Thus, a full understanding of their structure-property relationship may only be achieved through the application of a coherent suite of leading-edge experimental probes, coupled with the cogent use of advanced computer simulation methods. Using as an exemplar a calcia-silica sol-gel glass of the kind developed by Larry Hench, in the memory of whom this paper is dedicated, we illustrate the successful use of high-energy X-ray and neutron scattering (diffraction) methods, magic-angle spinning solid-state NMR, and molecular dynamics simulation as components to a powerful methodology for the study of amorphous materials.

Determinisztikus és valószínűségi elosztási eljárások (Deterministic and probabilistic rationing methods)

Az életben számtalan olyan esettel találkozunk, amikor egy jószág iránti kereslet meghaladja a rendelkezésre álló kínálatot. Példaként említhetjük a kárpótlási igényeket, egy csődbement cég hitelezőinek igényeit, valamely szerv átültetésére váró betegek sorát stb. Ilyen helyzetekben valamilyen eljárás szerint oszthatjuk el a szűkös mennyiséget a szereplők között. Szokás megkülönböztetni a determinisztikus és a sztochasztikus elosztási eljárásokat, jóllehet sok esetben csak a determinisztikus eljárásokat alkalmazzák. Azonban igazságossági szempontból gyakran használnak sztochasztikus elosztási eljárásokat is, mint például tette azt az Egyesült államok hadserege a második világháború végét követően a külföldön állomásozó katonáinak visszavonásakor, illetve a vietnami háború során behívandó személyek kiválasztásakor. / === / We investigated the minimal variance methods introduced in Tasnádi [6] based on seven popular axioms. We proved that if a deterministic rationing method satisfies demand monotonicity, resource monotonicity, equal treatment of equals and self-duality, than the minimal variance methods associated with the given deterministic rationing method also satisfies demand monotonicity, resource monotonicity, equal treatment of equals and self-duality. Furthermore, we found that the consistency, the lower composition and the upper composition of a deterministic rationing method does not imply the consistency, the lower composition and the upper composition of a minimal variance method associated with the given deterministic rationing method.

The applied computer science of economic analyses: Internet prioritization and Internet pricing, and software engineering and software pricing for the mass market

This research examines evolving issues in applied computer science and applies economic and business analyses as well. There are two main areas. The first is internetwork communications as embodied by the Internet. The goal of the research is to devise an efficient pricing, prioritization, and incentivization plan that could be realistically implemented on the existing infrastructure. Criteria include practical and economic efficiency, and proper incentives for both users and providers. Background information on the evolution and functional operation of the Internet is given, and relevant literature is surveyed and analyzed. Economic analysis is performed on the incentive implications of the current pricing structure and organization. The problems are identified, and minimally disruptive solutions are proposed for all levels of implementation to the lowest level protocol. Practical issues are considered and performance analyses are done. The second area of research is mass market software engineering, and how this differs from classical software engineering. Software life-cycle revenues are analyzed and software pricing and timing implications are derived. A profit maximizing methodology is developed to select or defer the development of software features for inclusion in a given release. An iterative model of the stages of the software development process is developed, taking into account new communications capabilities as well as profitability. ^

Improved estimation of postmortem interval with Cardiac Troponin T and improved analytical methods

Accurate knowledge of the time since death, or postmortem interval (PMI), has enormous legal, criminological, and psychological impact. In this study, an investigation was made to determine whether the relationship between the degradation of the human cardiac structure protein Cardiac Troponin T and PMI could be used as an indicator of time since death, thus providing a rapid, high resolution, sensitive, and automated methodology for the determination of PMI. ^ The use of Cardiac Troponin T (cTnT), a protein found in heart tissue, as a selective marker for cardiac muscle damage has shown great promise in the determination of PMI. An optimized conventional immunoassay method was developed to quantify intact and fragmented cTnT. A small sample of cardiac tissue, which is less affected than other tissues by external factors, was taken, homogenized, extracted with magnetic microparticles, separated by SDS-PAGE, and visualized with Western blot by probing with monoclonal antibody against cTnT. This step was followed by labeling and available scanners. This conventional immunoassay provides a proper detection and quantitation of cTnT protein in cardiac tissue as a complex matrix; however, this method does not provide the analyst with immediate results. Therefore, a competitive separation method using capillary electrophoresis with laser-induced fluorescence (CE-LIF) was developed to study the interaction between human cTnT protein and monoclonal anti-TroponinT antibody. ^ Analysis of the results revealed a linear relationship between the percent of degraded cTnT and the log of the PMI, indicating that intact cTnT could be detected in human heart tissue up to 10 days postmortem at room temperature and beyond two weeks at 4C. The data presented demonstrates that this technique can provide an extended time range during which PMI can be more accurately estimated as compared to currently used methods. The data demonstrates that this technique represents a major advance in time of death determination through a fast and reliable, semi-quantitative measurement of a biochemical marker from an organ protected from outside factors. ^

Synthesis and Biological Evaluation of Novel Folic Acid Receptor-Targeted, β-Cyclodextrin-Based Drug Complexes for Cancer Treatment

Drug targeting is an active area of research and nano-scaled drug delivery systems hold tremendous potential for the treatment of neoplasms. In this study, a novel cyclodextrin (CD)-based nanoparticle drug delivery system has been assembled and characterized for the therapy of folate receptor-positive [FR(+)] cancer. Water-soluble folic acid (FA)-conjugated CD carriers (FACDs) were successfully synthesized and their structures were confirmed by 1D/2D nuclear magnetic resonance (NMR), matrix-assisted laser desorption ionization time-of-flight mass spectrometer (MALDI-TOF-MS), high performance liquid chromatography (HPLC), Fourier transform infrared spectroscopy (FTIR), and circular dichroism. Drug complexes of adamatane (Ada) and cytotoxic doxorubicin (Dox) with FACD were readily obtained by mixed solvent precipitation. The average size of FACD-Ada-Dox was 1.5–2.5 nm. The host-guest association constant Ka was 1,639 M−1 as determined by induced circular dichroism and the hydrophilicity of the FACDs was greatly enhanced compared to unmodified CD. Cellular uptake and FR binding competitive experiments demonstrated an efficient and preferentially targeted delivery of Dox into FR-positive tumor cells and a sustained drug release profile was seen in vitro. The delivery of Dox into FR(+) cancer cells via endocytosis was observed by confocal microscopy and drug uptake of the targeted nanoparticles was 8-fold greater than that of non-targeted drug complexes. Our docking results suggest that FA, FACD and FACD-Ada-Dox could bind human hedgehog interacting protein that contains a FR domain. Mouse cardiomyocytes as well as fibroblast treated with FACD-Ada-Dox had significantly lower levels of reactive oxygen species, with increased content of glutathione and glutathione peroxidase activity, indicating a reduced potential for Dox-induced cardiotoxicity. These results indicate that the targeted drug complex possesses high drug association and sustained drug release properties with good biocompatibility and physiological stability. The novel FA-conjugated β-CD based drug complex might be promising as an anti-tumor treatment for FR(+) cancer.

Pre-formulation and systematic evaluation of amino acid assisted permeability of insulin across in vitro buccal cell layers

The aim of this work was to investigate alternative safe and effective permeation enhancers for buccal peptide delivery. Basic amino acids improved insulin solubility in water while 200 and 400 µg/mL lysine significantly increased insulin solubility in HBSS. Permeability data showed a significant improvement in insulin permeation especially for 10 µg/mL of lysine (p < 0.05) and 10 µg/mL histidine (p < 0.001), 100 µg/mL of glutamic acid (p < 0.05) and 200 µg/mL of glutamic acid and aspartic acid (p < 0.001) without affecting cell integrity; in contrast to sodium deoxycholate which enhanced insulin permeability but was toxic to the cells. It was hypothesized that both amino acids and insulin were ionised at buccal cavity pH and able to form stable ion pairs which penetrated the cells as one entity; while possibly triggering amino acid nutrient transporters on cell surfaces. Evidence of these transport mechanisms was seen with reduction of insulin transport at suboptimal temperatures as well as with basal-to-apical vectoral transport, and confocal imaging of transcellular insulin transport. These results obtained for insulin is the first indication of a possible amino acid mediated transport of insulin via formation of insulin-amino acid neutral complexes by the ion pairing mechanism.

Characterization of resistivity of Sb2S3 semiconductor nanowires by conductive AFM and in-situ methods

Conductive AFM and in situ methods were used to determine contact resistance and resistivity of individual Sb2S3 nanowires. Nanowires were deposited on oxidized Si surface for in situ measurements and on Si surface with macroelectrodes for conductive AFM (C-AFM) measurements. Contact resistance was determined by measurement of I(V) characteristics at different distances from the nanowire contact with the macroelectrode and resistivity of nanowires was determined. Sb2S3 is a soft material with low adhesion force to the surface and therefore special precautions were taken during measurements.

Exploration of the relationship between tacit knowledge and software system test complexity

This research has explored the relationship between system test complexity and tacit knowledge. It is proposed as part of this thesis, that the process of system testing (comprising of test planning, test development, test execution, test fault analysis, test measurement, and case management), is directly affected by both complexity associated with the system under test, and also by other sources of complexity, independent of the system under test, but related to the wider process of system testing. While a certain amount of knowledge related to the system under test is inherent, tacit in nature, and therefore difficult to make explicit, it has been found that a significant amount of knowledge relating to these other sources of complexity, can indeed be made explicit. While the importance of explicit knowledge has been reinforced by this research, there has been a lack of evidence to suggest that the availability of tacit knowledge to a test team is of any less importance to the process of system testing, when operating in a traditional software development environment. The sentiment was commonly expressed by participants, that even though a considerable amount of explicit knowledge relating to the system is freely available, that a good deal of knowledge relating to the system under test, which is demanded for effective system testing, is actually tacit in nature (approximately 60% of participants operating in a traditional development environment, and 60% of participants operating in an agile development environment, expressed similar sentiments). To cater for the availability of tacit knowledge relating to the system under test, and indeed, both explicit and tacit knowledge required by system testing in general, an appropriate knowledge management structure needs to be in place. This would appear to be required, irrespective of the employed development methodology.

Wind Resource Mapping Using Landscape Roughness and Spatial Interpolation Methods

Energy saving, reduction of greenhouse gasses and increased use of renewables are key policies to achieve the European 2020 targets. In particular, distributed renewable energy sources, integrated with spatial planning, require novel methods to optimise supply and demand. In contrast with large scale wind turbines, small and medium wind turbines (SMWTs) have a less extensive impact on the use of space and the power system, nevertheless, a significant spatial footprint is still present and the need for good spatial planning is a necessity. To optimise the location of SMWTs, detailed knowledge of the spatial distribution of the average wind speed is essential, hence, in this article, wind measurements and roughness maps were used to create a reliable annual mean wind speed map of Flanders at 10 m above the Earth’s surface. Via roughness transformation, the surface wind speed measurements were converted into meso- and macroscale wind data. The data were further processed by using seven different spatial interpolation methods in order to develop regional wind resource maps. Based on statistical analysis, it was found that the transformation into mesoscale wind, in combination with Simple Kriging, was the most adequate method to create reliable maps for decision-making on optimal production sites for SMWTs in Flanders (Belgium).

Identification and bioactivity evaluation of two novel temporins from the skin secretion of the European edible frog, Pelophylax kl. Esculentus

The amphibian temporins, amongst the smallest antimicrobial peptides (AMPs), are α-helical, amphipathic, hydrophobic and cationic and are active mainly against Gram-positive bacteria but inactive or weakly active against Gram-negative bacteria. Here, we report two novel members of the temporin family, named temporin-1Ee (FLPVIAGVLSKLFamide) and temporin-1Re (FLPGLLAGLLamide), whose biosynthetic precursor structures were deduced from clones obtained from skin secretion-derived cDNA libraries of the European edible frog, Pelophylax kl. esculentus, by ‘shotgun’ cloning. Deduction of the molecular masses of each mature processed peptide from respective cloned cDNAs was used to locate respective molecules in reverse-phase HPLC fractions of secretion. Temporin-1Ee (MIC = 10 μM) and temporin-1Re (MIC = 60 μM) were both found to be active against Gram-positive Staphylococcus aureus, but retaining a weak haemolytic activity. To our knowledge, Single-site substitutions can dramatically change the spectrum of activity of a given temporin. Compared with temporine-1Ec, just one chemically-conservative substitution (Val8 instead of Leu8), temporin-1Ee bearing a net charge of +2 displays broad-spectrum activity with particularly high potency on the clinically relevant Gram-negative strains, Escherichia coli (MIC = 40 μM). These factors bode well for translating temporins to be potential drug candidates for the design of new and valuable anti-infective agents.

Applying the expanding photosphere and standardized candle methods to Type II-Plateau supernovae at cosmologically significant redshifts . The distance to SN 2013eq

Based on optical imaging and spectroscopy of the Type II-Plateau SN 2013eq, we present a comparative study of commonly used distance determination methods based on Type II supernovae. The occurrence of SN 2013eq in the Hubble flow (z = 0.041 ± 0.001) prompted us to investigate the implications of the difference between "angular" and "luminosity" distances within the framework of the expanding photosphere method (EPM) that relies upon a relation between flux and angular size to yield a distance. Following a re-derivation of the basic equations of the EPM for SNe at non-negligible redshifts, we conclude that the EPM results in an angular distance. The observed flux should be converted into the SN rest frame and the angular size, θ, has to be corrected by a factor of (1 + z)2. Alternatively, the EPM angular distance can be converted to a luminosity distance by implementing a modification of the angular size. For SN 2013eq, we find EPM luminosity distances of DL = 151 ± 18 Mpc and DL = 164 ± 20 Mpc by making use of different sets of dilution factors taken from the literature. Application of the standardized candle method for Type II-P SNe results in an independent luminosity distance estimate (DL = 168 ± 16 Mpc) that is consistent with the EPM estimate. Spectra of SN 2013eq are available in the Weizmann Interactive Supernova data REPository (WISeREP): http://wiserep.weizmann.ac.il