Machine-driven parameter screen of biochemical reactions

The development of complex methods in molecular biology is a laborious, costly, iterative and often intuition-bound process where optima are sought in a multidimensional parameter space through step-by-step optimizations. The difficulty of miniaturizing reactions under the microliter volumes usually handled in multiwell plates by robots, plus the cost of the experiments, limit the number of parameters and the dynamic ranges that can be explored. Nevertheless, because of non-linearities of the response of biochemical systems to their reagent concentrations, broad dynamic ranges are necessary. Here we use a high-performance nanoliter handling platform and computer generation of liquid transfer programs to explore in quadruplicates 648 combinations of 4 parameters of a biochemical reaction, the reverse-transcription, which lead us to uncover non-linear responses, parameter interactions and novel mechanistic insights. With the increased availability of computer-driven laboratory platforms for biotechnology, our results demonstrate the feasibility and advantage of methods development based on reproducible, computer-aided exhaustive characterization of biochemical systems.

Machine-driven parameter optimisation of biochemical reactions

The development of complex, multi-step methods in molecular biology is a laborious, costly, iterative and often intuition-bound process where an optimum is sought in a multidimensional parameter space through step-by-step optimisations. The difficulty of miniaturising reactions under the microliter volumes usually handled in multiwell plates by robots, plus the cost of the experiments, limit the number of parameters and the dynamic ranges that can be explored. Nevertheless, because of non-linearities of the response of biochemical systems to their reagent concentrations, broad dynamic ranges are necessary. Here we use a high-performance nanoliter handling platform and computer generation of liquid transfer programs to explore in quadruplicates more than 600 combinations of 4 parameters of a biochemical reaction, the reverse-transcription, which lead us to uncover non-linear responses, parameter interactions and novel mechanistic insights. With the increased availability of computer-driven laboratory platforms for biotechnology, our results demonstrate the feasibility and advantage of methods development based on reproducible, computer-aided exhaustive characterisation of biochemical systems.

Computer Generation of Birds of a Feather Puzzles

In this article, we describe a computer-aided design process for generating high-quality Birds of a Feather solitaire card puzzles. In each iteration, we generate puzzles via combinatorial optimization of an objective function. After solving and subjectively rating such puzzles, we compute objective puzzle features and regress our ratings onto such features to provide insight for objective function improvements. Through this iterative improvement process, we demonstrate the importance of the halfway solvability ratio in quality puzzle design. We relate our observations to recent work on tension in puzzle design, and suggest next steps for more efficient puzzle generation.

The Architectonics of Musical Sound

At the turn of the 20th and 21st centuries there appeared a new trend in musical composition and musical pedagogy conditioned by the fast development of electronic musical instruments: from the simplest synthesizers to powerful musical computers. In the wide range contemporary electronic musical instrument the accumulated informational technologies in music and the art of music making have manifested themselves in the fullest and most perfect manner. The current and the subsequent issues of the journal shall provide a consecutive presentation of four lectures, compiling the basis of the discipline “Informational Technologies in Music” and a set of programs of advanced training, which include “Informational Technologies in Music,” “Informational Technologies in Musical Education,” “Computer Musical Composition,” etc. The first lecture, “The Architectonics of Musical Sound” shall disclose themes connected with the study of the physical characteristics of musical sounds, the means of their recording and reproduction; explanation is given to the aural perception of sound by the human being, and the basic principles of computer generation of musical sound are examined. The material elucidated in the lection possesses a theoretical and practical directedness and contains information in which the technological aspects of contemporary perceptions of music, about the musical instrument range (including computer musical instruments); without knowledge of these aspects a competent interpretation of musical instruments is impossible.