An Algorithm for Solving Alive Situation Puzzles in GO Game

Article信州大学工学部紀要 65: 17-24 (1989)departmental bulletin pape

Development and Characterization of Gastro-Intestinal Simulator (GIS)

For oral drug formulations, the efficacy of a formulation in an individual is dependent on many physiological processes and variables. For most immediate release drug products, the formulation must disintegrate and dissolve, undissolved mass must empty from the stomach into the upper gastrointestinal (GI) tract, and remaining undissolved drug must dissolve and be absorbed across the intestinal wall to reach systemic circulation. Despite understanding the relevant processes, conventional in vitro methods only capture a part of these processes by performing dissolution at one pH without any other processes acting on the formulation. In this work, a dissolution device is developed that simulates the relevant in vivo processes that can affect drug dissolution. This device is called the Gastro-Intestinal Simulator or (GIS) and is designed to simulate in vivo conditions in a way that maintains ease of use. Compared to other multi-vessel dissolution devices, the GIS can be run multiple times in a day by just one analyst. The device has been designed with customizability in mind, with the ability for vessel geometry to be easily selected, a variety of gastric emptying rates applied, and a titration function to maintain pH in the chamber representing the upper intestine (e.g. duodenum) when using biorelevant media. Applications of the device were evaluated with two sets of experiments: determination of in vitro – in vivo correlations (IVIVC), and formulation screening tests to determine sensitivity to formulation variables and results compared to conventional testing procedures. IVIVCs are a valuable tool in quantifying drug release into systemic circulation but require physiologically relevant dissolution data. The dissolution data generated for two ibuprofen formulations in the GIS did not produce a successful IVIVC. Although the results of this work failed to meet strict FDA requirements for an IVIVC, the results showed promise and provide a framework for future correlative dissolution. The GIS system has the capability for further optimization to better represent the conditions of the human intestine, which could allow for improved correlations including biorelevant media selection, gastric emptying, and introduction of an absorption compartment. For formulation optimization, a similar framework as other industrial process optimizations can be applied. However, multiple process and formulation variables increases the challenge of developing an understanding of these effects and therefore benefits from an appropriate experimental design. This empirical approach requires a statistical design of experiments and a Plackett-Burman design was selected as a screening approach designed to limit the number of experiments to determine the main effects of interest. The GIS results showed the most statistically significant factors compared to compendial disintegration and dissolution methods. In both applications, the GIS, when configured to simulate the relevant conditions of the human intestine showed significant promise for assessing formulations and mechanisms that lead to improved in vivo drug dissolution.PHDPharmaceutical SciencesUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/163054/1/njob_1.pd

The Frontier of Decidability in Partially Observable Recursive Games

revised 2011, accepted 2011, in pressInternational audienceThe classical decision problem associated with a game is whether a given player has a winning strategy, i.e. some strategy that leads almost surely to a victory, regardless of the other players' strategies. While this problem is relevant for deterministic fully observable games, for a partially observable game the requirement of winning with probability 1 is too strong. In fact, as shown in this paper, a game might be decidable for the simple criterion of almost sure victory, whereas optimal play (even in an approximate sense) is not computable. We therefore propose another criterion, the decidability of which is equivalent to the computability of approximately optimal play. Then, we show that (i) this criterion is undecidable in the general case, even with deterministic games (no random part in the game), (ii) that it is in the jump 0', and that, even in the stochastic case, (iii) it becomes decidable if we add the requirement that the game halts almost surely whatever maybe the strategies of the players

Regional Intestinal Drug Absorption

The gastrointestinal tract (GIT) can be broadly divided into several regions: the stomach, the small intestine (which is subdivided to duodenum, jejunum, and ileum), and the colon. The conditions and environment in each of these segments, and even within the segment, are dependent on many factors, e.g., the surrounding pH, fluid composition, transporters expression, metabolic enzymes activity, tight junction resistance, different morphology along the GIT, variable intestinal mucosal cell differentiation, changes in drug concentration (in cases of carrier-mediated transport), thickness and types of mucus, and resident microflora. Each of these variables, alone or in combination with others, can fundamentally alter the solubility/dissolution, the intestinal permeability, and the overall absorption of various drugs. This is the underlying mechanistic basis of regional-dependent intestinal drug absorption, which has led to many attempts to deliver drugs to specific regions throughout the GIT, aiming to optimize drug absorption, bioavailability, pharmacokinetics, and/or pharmacodynamics. In the book "Regional Intestinal Drug Absorption: Biopharmaceutics and Drug Formulation" we aim to highlight the current progress and to provide an overview of the latest developments in the field of regional-dependent intestinal drug absorption and delivery, as well as pointing out the unmet needs of the field

Context and change in Japanese music

Although Japan is often portrayed as culturally and ethnically highly homogeneous, its music culture has long been extremely diverse, especially so with modernization and globalization. Thus we begin by problematizing the term ‘Japanese music’. We then aim to provide broad historical, cultural and theoretical contexts within which to understand the subsequent genre-specific chapters, by introducing a range of cross-cutting topics, issues and research perspectives - for example: Japan’s interactions with other cultures throughout history; sociocultural contexts of each genre, including issues of patronage, audiences, class and gender; social structures and mechanisms of transmission; music theory in Japan; aesthetic concepts; and research culture. We conclude with a view into the musical future, considering the impact of educational policies, globalization and so forth

Bandit-Based Genetic Programming

International audienceWe consider the validation of randomly generated patterns in a Monte-Carlo Tree Search program. Our bandit-based genetic programming (BGP) algorithm, with proved mathematical properties, outperformed a highly optimized handcrafted module of a well-known computer-Go program with several world records in the game of Go