Piano Genie

We present Piano Genie, an intelligent controller which allows non-musicians to improvise on the piano. With Piano Genie, a user performs on a simple interface with eight buttons, and their performance is decoded into the space of plausible piano music in real time. To learn a suitable mapping procedure for this problem, we train recurrent neural network autoencoders with discrete bottlenecks: an encoder learns an appropriate sequence of buttons corresponding to a piano piece, and a decoder learns to map this sequence back to the original piece. During performance, we substitute a user's input for the encoder output, and play the decoder's prediction each time the user presses a button. To improve the intuitiveness of Piano Genie's performance behavior, we impose musically meaningful constraints over the encoder's outputs.Comment: Published as a conference paper at ACM IUI 201

Prevalence and consequences of patient safety incidents in general practice in the Netherlands: a retrospective medical record review study

BACKGROUND Patient safety can be at stake in both hospital and general practice settings. While severe patient safety incidents have been described, quantitative studies in large samples of patients in general practice are rare. This study aimed to assess patient safety in general practice, and to show areas where potential improvements could be implemented. METHODS We conducted a retrospective review of patient records in Dutch general practice. A random sample of 1,000 patients from 20 general practices was obtained. The number of patient safety incidents that occurred in a one-year period, their perceived underlying causes, and impact on patients' health were recorded. RESULTS We identified 211 patient safety incidents across a period of one year (95% CI: 185 until 241). A variety of types of incidents, perceived causes and consequences were found. A total of 58 patient safety incidents affected patients; seven were associated with hospital admission; none resulted in permanent disability or death. CONCLUSIONS Although this large audit of medical records in general practices identified many patient safety incidents, only a few had a major impact on patients' health. Improving patient safety in this low-risk environment poses specific challenges, given the high numbers of patients and contacts in general practice.The Dutch Ministry of Health, Welfare and Sport (VWS) initiated the project and supported the project financially (without restrictions on the scientific work; grant number 313741)

mRNA turnover rate limits siRNA and microRNA efficacy

Based on a simple model of the mRNA life cycle, we predict that mRNAs with high turnover rates in the cell are more difficult to perturb with RNAi. We test this hypothesis using a luciferase reporter system and obtain additional evidence from a variety of large-scale data sets, including microRNA overexpression experiments and RT–qPCR-based efficacy measurements for thousands of siRNAs. Our results suggest that mRNA half-lives will influence how mRNAs are differentially perturbed whenever small RNA levels change in the cell, not only after transfection but also during differentiation, pathogenesis and normal cell physiology

Determinants of protein function revealed by combinatorial entropy optimization

A new algorithm is presented allows protein specificity residues to be assigned from multiple sequence alignments alone. This information can be used, amongst other things, to infer protein functions

The Amino-Acid Mutational Spectrum of Human Genetic Disease

Background: Nonsynonymous mutations in the coding regions of human genes are responsible for phenotypic differences between humans and for susceptibility to genetic disease. Computational methods were recently used to predict deleterious effects of nonsynonymous human mutations and polymorphisms. Here we focus on understanding the amino-acid mutation spectrum of human genetic disease. We compare the disease spectrum to the spectra of mutual amino-acid mutation frequencies, non-disease polymorphisms in human genes, and substitutions fixed between species. Results: We find that the disease spectrum correlates well with the amino-acid mutation frequencies based on the genetic code. Normalized by the mutation frequencies, the spectrum can be rationalized in terms of chemical similarities between amino acids. The disease spectrum is almost identical for membrane and non-membrane proteins. Mutations at arginine and glycine residues are together responsible for about 30% of genetic diseases, whereas random mutations at tryptophan and cysteine have the highest probability of causing disease. Conclusions: The overall disease spectrum mainly reflects the mutability of the genetic code. We corroborate earlier results that the probability of a nonsynonymous mutation causing a genetic disease increases monotonically with an increase in the degree of evolutionary conservation of the mutation site and a decrease in the solvent-accessibility of the site; opposite trends are observed for non-disease polymorphisms. We estimate that the rate of nonsynonymous mutations with a negative impact on human health is less than one per diploid genome per generation