Agent-orientated auction mechanism and strategy design

Agent-based technology is playing an increasingly important role in today’s economy. Usually a multi-agent system is needed to model an economic system such as a market system, in which heterogeneous trading agents interact with each other autonomously. Two questions often need to be answered regarding such systems: 1) How to design an interacting mechanism that facilitates efficient resource allocation among usually self-interested trading agents? 2) How to design an effective strategy in some specific market mechanisms for an agent to maximise its economic returns? For automated market systems, auction is the most popular mechanism to solve resource allocation problems among their participants. However, auction comes in hundreds of different formats, in which some are better than others in terms of not only the allocative efficiency but also other properties e.g., whether it generates high revenue for the auctioneer, whether it induces stable behaviour of the bidders. In addition, different strategies result in very different performance under the same auction rules. With this background, we are inevitably intrigued to investigate auction mechanism and strategy designs for agent-based economics. The international Trading Agent Competition (TAC) Ad Auction (AA) competition provides a very useful platform to develop and test agent strategies in Generalised Second Price auction (GSP). AstonTAC, the runner-up of TAC AA 2009, is a successful advertiser agent designed for GSP-based keyword auction. In particular, AstonTAC generates adaptive bid prices according to the Market-based Value Per Click and selects a set of keyword queries with highest expected profit to bid on to maximise its expected profit under the limit of conversion capacity. Through evaluation experiments, we show that AstonTAC performs well and stably not only in the competition but also across a broad range of environments. The TAC CAT tournament provides an environment for investigating the optimal design of mechanisms for double auction markets. AstonCAT-Plus is the post-tournament version of the specialist developed for CAT 2010. In our experiments, AstonCAT-Plus not only outperforms most specialist agents designed by other institutions but also achieves high allocative efficiencies, transaction success rates and average trader profits. Moreover, we reveal some insights of the CAT: 1) successful markets should maintain a stable and high market share of intra-marginal traders; 2) a specialist’s performance is dependent on the distribution of trading strategies. However, typical double auction models assume trading agents have a fixed trading direction of either buy or sell. With this limitation they cannot directly reflect the fact that traders in financial markets (the most popular application of double auction) decide their trading directions dynamically. To address this issue, we introduce the Bi-directional Double Auction (BDA) market which is populated by two-way traders. Experiments are conducted under both dynamic and static settings of the continuous BDA market. We find that the allocative efficiency of a continuous BDA market mainly comes from rational selection of trading directions. Furthermore, we introduce a high-performance Kernel trading strategy in the BDA market which uses kernel probability density estimator built on historical transaction data to decide optimal order prices. Kernel trading strategy outperforms some popular intelligent double auction trading strategies including ZIP, GD and RE in the continuous BDA market by making the highest profit in static games and obtaining the best wealth in dynamic games.

Novel bioactive scaffolds incorporating nanogels as potential drug eluting devices

Big advances are being achieved in the design of new implantable devices with enhanced properties. For example, synthetic porous three-dimensional structures can mimic the architecture of the tissues, and serve as templates for cell seeding. In addition, polymeric nanoparticles are able to provide a programmable and sustained local delivery of different types of biomolecules. In this study novel alternative scaffolds with controlled bioactive properties and architectures are presented. Two complementary approaches are described. Firstly, scaffolds with nanogels as active controlled release devices incorporated inside the three-dimensional structure are obtained using the thermally induced phase separation (TIPS) method. Secondly, a novel coating method using the spraying technique to load these nanometric crosslinked hydrogels on the surface of two-dimensional (2D) and three-dimensional (3D) biodegradable scaffolds is described. The scanning electron microscopy (SEM) images show the distribution of the nanogels on the surface of different substrates and also inside the porous structure of poly-a-hydroxy ester derivative foams. Both of them are compared in terms of manufacturability, dispersion and other processing variables.

Design and evaluation of compound metformin/glipizide elementary osmotic pump tablets

A simple elementary osmotic pump (EOP) system that could deliver metformin hydrochloride (MT) and glipizide (GZ) simultaneously for extended periods of time was developed in order to reduce the problems associated with multidrug therapy of type 2 non-insulin-dependent diabetes mellitus. In general, both highly and poorly water-soluble drugs are not good candidates for elementary osmotic delivery. However, MT is a highly soluble drug with a high dose (500 mg) while GZ is a water-insoluble drug with a low dose (5 mg) so it is a great challenge to pharmacists to provide satisfactory extended release of MT and GZ. In this paper sodium carbonate was used to modulate the solubility of GZ within the core and MT was not only one of the active ingredients but also the osmotic agent. The optimal EOP was found to deliver both drugs at a rate of approximately zero order for up to 10 h in pH 6.8, independent of environment media. In-vivo evaluation was performed relative to the equivalent dose of conventional MT tablet and GZ tablet by a cross-study in six Beagle dogs. The EOP had a good sustained effect in comparison with the conventional product. The prototype design of the system could be applied to other combinations of drugs used for cardiovascular diseases, diabetes, etc.

Design of Fractional Order Digital Differentiators and Integrators Using Indirect Discretization

Mathematics Subject Classification: 26A33, 93B51, 93C95

Drug repurposing screen identifies Foxo1-dependent angiopoietin-2 regulation in sepsis

Objective: The recent withdrawal of a targeted sepsis therapy has diminished pharmaceutical enthusiasm for developing novel drugs for the treatment of sepsis. Angiopoietin-2 is an endothelial-derived protein that potentiates vascular inflammation and leakage and may be involved in sepsis pathogenesis. We screened approved compounds for putative inhibitors of angiopoietin-2 production and investigated underlying molecular mechanisms. Design: Laboratory and animal research plus prospective placebo-controlled randomized controlled trial (NCT00529139) and retrospective analysis (NCT00676897). Setting: Research laboratories of Hannover Medical School and Harvard Medical School. Patients: Septic patients/C57Bl/6 mice and human endothelial cells. Interventions: Food and Drug Administration-approved library screening. Measurements and Main Results: In a cell-based screen of more than 650 Food and Drug Administration-approved compounds, we identified multiple members of the 3-hydroxy-3-methyl-glutaryl-CoA reductase inhibitor drug class (referred to as statins) that suppressed angiopoietin-2. Simvastatin inhibited 3-hydroxy-3-methyl-glutaryl-CoA reductase, which in turn activated PI3K-kinase. Downstream of this signaling, PI3K-dependent phosphorylation of the transcription factor Foxo1 at key amino acids inhibited its ability to shuttle to the nucleus and bind cis-elements in the angiopoietin-2 promoter. In septic mice, transient inhibition of angiopoietin-2 expression by liposomal siRNA in vivo improved absolute survival by 50%. Simvastatin had a similar effect, but the combination of angiopoietin-2 siRNA and simvastatin showed no additive benefit. To verify the link between statins and angiopoietin-2 in humans, we performed a pilot matched case-control study and a small randomized placebo-controlled trial demonstrating beneficial effects on angiopoietin-2. Conclusions: 3-hydroxy-3-methyl-glutaryl-CoA reductase inhibitors may operate through a novel Foxo1-angiopoietin-2 mechanism to suppress de novo production of angiopoietin-2 and thereby ameliorate manifestations of sepsis. Given angiopoietin-2's dual role as a biomarker and candidate disease mediator, early serum angiopoietin-2 measurement may serve as a stratification tool for future trials of drugs targeting vascular leakage.

Does anticholinergics drug burden relate to global neuro-disability outcome measures and length of hospital stay?

Primary objective: To assess the relationship between disability, length of stay (LOS) and anticholinergic burden (ACB) with people following acquired brain or spinal cord injury. Research design: A retrospective case note review assessed total rehabilitation unit admission. Methods and procedures: Assessment of 52 consecutive patients with acquired brain/spinal injury and neuropathy in an in-patient neuro-rehabilitation unit of a UK university hospital. Data analysed included: Northwick Park Dependency Score (NPDS), Rehabilitation complexity Scale (RCS), Functional Independence Measure and Functional Assessment Measure FIM-FAM (UK version 2.2), LOS and ACB. Outcome was different in RCS, NPDS and FIM-FAM between admission and discharge. Main outcomes and results: A positive change was reported in ACB results in a positive change in NPDS, with no significant effect on FIM-FAM, either Motor or Cognitive, or on the RCS. Change in ACB correlated to the length of hospital stay (regression correlation = −6.64; SE = 3.89). There was a significant harmful impact of increase in ACB score during hospital stay, from low to high ACB on NPDS (OR = 9.65; 95% CI = 1.36–68.64) and FIM-FAM Total scores (OR = 0.03; 95% CI = 0.002–0.35). Conclusions: There was a statistically significant correlation of ACB and neuro-disability measures and LOS amongst this patient cohort.

Functionalised particles using dry powder coating in pharmaceutical drug delivery:promises and challenges

Introduction: Production of functionalised particles using dry powder coating is a one-step, environmentally friendly process that paves the way for the development of particles with targeted properties and diverse functionalities. Areas covered: Applying the first principles in physical science for powders, fine guest particles can be homogeneously dispersed over the surface of larger host particles to develop functionalised particles. Multiple functionalities can be modified including: flowability, dispersibility, fluidisation, homogeneity, content uniformity and dissolution profile. The current publication seeks to understand the fundamental underpinning principles and science governing dry coating process, evaluate key technologies developed to produce functionalised particles along with outlining their advantages, limitations and applications and discusses in detail the resultant functionalities and their applications. Expert opinion: Dry particle coating is a promising solvent-free manufacturing technology to produce particles with targeted functionalities. Progress within this area requires the development of continuous processing devices that can overcome challenges encountered with current technologies such as heat generation and particle attrition. Growth within this field requires extensive research to further understand the impact of process design and material properties on resultant functionalities.

Patients' and physicians' experiences of atrial fibrillation consultations and anticoagulation decision-making:a multi-perspective IPA design

OBJECTIVE: To explore patients' and physicians' experiences of atrial fibrillation consultations and oral anticoagulation decision-making. DESIGN: Multi-perspective interpretative phenomenological analyses. METHODS: Participants included small homogeneous subgroups: AF patients who accepted (n=4), refused (n=4), or discontinued (n=3) warfarin, and four physician subgroups (n=4 each group): consultant cardiologists, consultant general physicians, general practitioners and cardiology registrars. Semi-structured interviews were conducted. Transcripts were analysed using multi-perspective IPA analyses to attend to individuals within subgroups and making comparisons within and between groups. RESULTS: Three themes represented patients' experiences: Positioning within the physician-patient dyad, Health-life balance, and Drug myths and fear of stroke. Physicians' accounts generated three themes: Mechanised metaphors and probabilities, Navigating toward the 'right' decision, and Negotiating systemic factors. CONCLUSIONS: This multi-perspective IPA design facilitated an understanding of the diagnostic consultation and treatment decision-making which foregrounded patients' and physicians' experiences. We drew on Habermas' theory of communicative action to recommend broadening the content within consultations and shifting the focus to patients' life contexts. Interventions including specialist multidisciplinary teams, flexible management in primary care, and multifaceted interventions for information provision may enable the creation of an environment that supports genuine patient involvement and participatory decision-making.

Catalyst design for biorefining

The quest for sustainable resources to meet the demands of a rapidly rising global population while mitigating the risks of rising CO2 emissions and associated climate change, represents a grand challenge for humanity. Biomass offers the most readily implemented and low-cost solution for sustainable transportation fuels, and the only non-petroleum route to organic molecules for the manufacture of bulk, fine and speciality chemicals and polymers. To be considered truly sustainable, biomass must be derived fromresources which do not compete with agricultural land use for food production, or compromise the environment (e.g. via deforestation). Potential feedstocks include waste lignocellulosic or oil-based materials derived from plant or aquatic sources, with the so-called biorefinery concept offering the co-production of biofuels, platform chemicals and energy; analogous to today's petroleum refineries which deliver both high-volume/low-value (e.g. fuels and commodity chemicals) and lowvolume/ high-value (e.g. fine/speciality chemicals) products, thereby maximizing biomass valorization. This article addresses the challenges to catalytic biomass processing and highlights recent successes in the rational design of heterogeneous catalysts facilitated by advances in nanotechnology and the synthesis of templated porous materials, as well as the use of tailored catalyst surfaces to generate bifunctional solid acid/base materials or tune hydrophobicity.

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.

Különböző beszerzői magatartásminták a magyarországi kórházak körében (Behaviour of the Hungarian hospital in their relationship with drug suppliers.)

A szerzők kutatásának célja a magyar kórházak gyógyszerbeszállítókkal kapcsolatos magatartásának jobb megértése. A szervezeti viselkedés természetéből adódóan a szerzők kutatásukat a komplexitás paradigmájára támaszkodva (Mucchielli, 2004) végezték el. Ahhoz, hogy kórházak beszerzési döntéseinek komplex eljárásait megvizsgálják, egy vegyes kutatási módszer alkalmazására volt szükség. Elméleti háttérként az üzleti kapcsolatok értékének integrált modelljét alkalmazták. A tanulmányban bemutatják egy kvantitatív és egy kvalitatív kutatás eredményeit a magyarországi kórházak és a gyógyszerbeszállítók közötti üzleti kapcsolatokban. ________________ The main goal of this research is to better understand the behaviour of the Hungarian hospital in their relationship with drug suppliers. The nature of the organisational behaviour guides the authors to conduct their research on the complexity paradigm (Mucchielli, 2004). To be able to explore the complex procedure of purchasing decisions in the hospitals, they applied a research design based on mixed method research. As a theoretical background the authors used the integrated model of business relationship value. In their paper they introduce the results of a quantitative and a qualitative research about the business relationships between hospitals and drug suppliers in Hungary.

``This is your brain on drugs'': The public policy of anti -drug programming. An exploratory analysis of media and other sources of drug information for adolescents

In the 1980s, government agencies sought to utilize research on drug use prevention to design media campaigns. Enlisting the assistance of the national media, several campaigns were designed and initiated to bring anti-drug use messages to adolescents in the form of public service advertising. This research explores the sources of information selected by adolescents in grades 7 through 12 and how the selection of media and other sources of information relate to drug use behavior and attitudes and perceptions related to risk/harm and disapproval of friends' drug-using activities.^ Data collected from 1989 to 1992 in the Miami Coalition School Survey provided a random selection of secondary school studies. The responses of these students were analyzed using multivariate statistical techniques.^ Although many of the students selected media as the source for most of their information on the effects of drugs on the people who use them, the selection of media was found to be positively related to alcohol use and negatively related to marijuana use. The selection of friends, brothers, or sisters was a statistically significant source for adolescents who smoke cigarettes, use alcohol or marijuana.^ The results indicate that the anti-drug use messages received by students may be canceled out by media messages perceived to advocate substance use and that a more persuasive source of information for adolescents may be friends and siblings. As federal reports suggest that the economic costs of drug abuse will reach an estimated $150 billion by 1997 if current trends continue, prevention policy that addresses the glamorization of substance use remains a national priority. Additionally, programs that advocate prevention within the peer cluster must be supported, as peers are an influential source for both inspiring and possibly preventing drug use behavior. ^

Design rationnel de nanothermomètres programmables à base d’ADN

Développer de nouveaux nanomatériaux, interrupteurs et machines nanométriques sensibles à de petites variations de température spécifiques devrait être de grande utilité pour une multitude de domaines œuvrant dans la nanotechnologie. De plus, l’objectif est de convaincre le lecteur que les nanotechnologies à base d’ADN offrent d’énormes possibilités pour la surveillance de température en temps réel à l’échelle nanométrique. Dans la section Résultats, nous exploitons les propriétés de l’ADN pour créer des thermomètres versatiles, robustes et faciles à employer. En utilisant une série de nouvelles stratégies inspirées par la nature, nous sommes en mesure de créer des nanothermomètres d’ADN capables de mesurer des températures de 25 à 95°C avec une précision de <0.1°C. En créant de nouveaux complexes d’ADN multimériques, nous arrivons à développer des thermomètres ultrasensibles pouvant augmenter leur fluorescence 20 fois sur un intervalle de 7°C. En combinant plusieurs brins d’ADN avec des plages dynamiques différentes, nous pouvons former des thermomètres montrant une transition de phase linéaire sur 50°C. Finalement, la vitesse de réponse et la précision des thermomètres développés et leur réversibilité sont illustrées à l’aide d’une expérience de surveillance de température à l’intérieur d’un unique puits d’un appareil de qPCR. En conclusion, les applications potentielles de tels nanothermomètres en biologie synthétique, imagerie thermique cellulaire, nanomachines d’ADN et livraison contrôlée seront considérées.

Design, Synthesis, and Photophysical Investigation of Porphyrin-containing Polymer-wrapped Single-walled Carbon Nanotubes

Significant advances in understanding the fundamental photophysical behavior of single-walled carbon nanotubes (SWNTs) have been made possible by the development of ionic, conjugated aryleneethynylene polymers that helically wrap SWNTs with well-defined morphology. My contribution to this work was the design and synthesis of porphyrin-containing polymers and the photophysical investigation of the corresponding polymer-wrapped SWNTs. For these new constructs, the polymer acts as more than just a solubilization scaffold; such assemblies can provide benchmark data for evaluating spectroscopic signatures of energy and charge transfer events and lay the groundwork for further, rational development of polymers with precisely tuned redox properties and electronic coupling with the underlying SWNT. The first design to incorporate a zinc porphyrin into the polymer backbone, PNES-PZn, suffered from severe aggregation in solution and was redesigned to produce the porphyrin-containing polymer S-PBN-PZn. This polymer was utilized to helically wrap chirality-enriched (6,5) SWNTs, which resulted in significant quenching of the porphyrin-based fluorescence. Time-resolved spectroscopy revealed a simultaneous rise and decay of the porphyrin radical cation and SWNT electron polaron spectroscopic signatures indicative of photoinduced electron transfer. A new polymer, S-PBN(b)-Ph2PZn3, was then synthesized which incorporated a meso-ethyne linked zinc porphyrin trimer. By changing the absorption profile and electrochemical redox potentials of the polymer, the photophysical behavior of the corresponding polymer-wrapped (6,5)-SWNTs was dramatically changed, and the polymer-wrapped SWNTs no longer showed evidence for photoinduced electron transfer.

Development of Plasmonic Nanoplatforms for Diagnostics, Therapy, and Sensing

Recent advances in nanotechnology have led to the application of nanoparticles in a wide variety of fields. In the field of nanomedicine, there is great emphasis on combining diagnostic and therapeutic modalities into a single nanoparticle construct (theranostics). In particular, anisotropic nanoparticles have shown great potential for surface-enhanced Raman scattering (SERS) detection due to their unique optical properties. Gold nanostars are a type of anisotropic nanoparticle with one of the highest SERS enhancement factors in a non-aggregated state. By utilizing the distinct characteristics of gold nanostars, new plasmonic materials for diagnostics, therapy, and sensing can be synthesized. The work described herein is divided into two main themes. The first half presents a novel, theranostic nanoplatform that can be used for both SERS detection and photodynamic therapy (PDT). The second half involves the rational design of silver-coated gold nanostars for increasing SERS signal intensity and improving reproducibility and quantification in SERS measurements.

The theranostic nanoplatforms consist of Raman-labeled gold nanostars coated with a silica shell. Photosensitizer molecules for PDT can be loaded into the silica matrix, while retaining the SERS signal of the gold nanostar core. SERS detection and PDT are performed at different wavelengths, so there is no interference between the diagnostic and therapeutic modalities. Singlet oxygen generation (a measure of PDT effectiveness) was demonstrated from the drug-loaded nanocomposites. In vitro testing with breast cancer cells showed that the nanoplatform could be successfully used for PDT. When further conjugating the nanoplatform with a cell-penetrating peptide (CPP), efficacy of both SERS detection and PDT is enhanced.

The rational design of plasmonic nanoparticles for SERS sensing involved the synthesis of silver-coated gold nanostars. Investigation of the silver coating process revealed that preservation of the gold nanostar tips was necessary to achieve the increased SERS intensity. At the optimal amount of silver coating, the SERS intensity is increased by over an order of magnitude. It was determined that a majority of the increased SERS signal can be attributed to reducing the inner filter effect, as the silver coating process moves the extinction of the particles far away from the laser excitation line. To improve reproducibility and quantitative SERS detection, an internal standard was incorporated into the particles. By embedding a small-molecule dye between the gold and silver surfaces, SERS signal was obtained both from the internal dye and external analyte on the particle surface. By normalizing the external analyte signal to the internal reference signal, reproducibility and quantitative analysis are improved in a variety of experimental conditions.