A novel TTN deletion in a family with skeletal myopathy, facial weakness, and dilated cardiomyopathy.

BACKGROUND: Pathogenic variants in TTN (OMIM 188840), encoding the largest human protein, are known to cause dilated cardiomyopathy and several forms of skeletal myopathy. The clinical interpretation of TTN variants is challenging, however, due to the frequency of missense changes, variable testing and reporting practices in commercial laboratories, and incomplete understanding of the spectrum of TTN-related disease. METHODS: We report a heterozygous TTN deletion segregating in a family with an unusual skeletal myopathy phenotype associated with facial weakness, gait abnormality, and dilated cardiomyopathy. RESULTS: A novel 16.430 kb heterozygous deletion spanning part of the A- and M-bands of TTN was identified in the proband and his symptomatic son, as well as in an additional son whose symptoms were identified on clinical evaluation. The deletion was found to be de novo in the proband. CONCLUSION: Pathogenic variants in TTN may be an unrecognized cause of skeletal myopathy phenotypes, particularly when accompanied by dilated cardiomyopathy.

The perception of concurrent sound objects through the use of harmonic enhancement: a study of auditory attention.

When the frequency of one harmonic, in a sound composed of many harmonics, is briefly mistuned and then returned to the 'in-tune' frequency and phase, observers report hearing this harmonic as a separate tone long after the brief period of mistuning - a phenomenon called harmonic enhancement. Here, we examined the consequence of harmonic enhancement on listeners' ability to detect a brief amplitude notch embedded in one of the harmonics after the period of mistuning. When present, the notch was either on the enhanced harmonic or on a different harmonic. Detection was better on the enhanced harmonic than on a non-enhanced harmonic. This finding suggests that attention was drawn to the enhanced harmonic (which constituted a new sound object) thereby easing the processing of sound features (i.e., a notch) within that object. This is the first evidence of a functional consequence of the after-effect of transient mistuning on auditory perception. Moreover, the findings provide support for an attention-based explanation of the enhancement phenomenon.

Kalman filters improve LSTM network performance in problems unsolvable by traditional recurrent nets.

The long short-term memory (LSTM) network trained by gradient descent solves difficult problems which traditional recurrent neural networks in general cannot. We have recently observed that the decoupled extended Kalman filter training algorithm allows for even better performance, reducing significantly the number of training steps when compared to the original gradient descent training algorithm. In this paper we present a set of experiments which are unsolvable by classical recurrent networks but which are solved elegantly and robustly and quickly by LSTM combined with Kalman filters.

Finding downbeats with a relaxation oscillator.

A relaxation oscillator model of neural spiking dynamics is applied to the task of finding downbeats in rhythmical patterns. The importance of downbeat discovery or 'beat induction' is discussed, and the relaxation oscillator model is compared to other oscillator models. In a set of computer simulations the model is tested on 35 rhythmical patterns. The model performs well, making good predictions in 34 of 35 cases. In an analysis we identify some shortcomings of the model and relate model behavior to dynamical properties of relaxation oscillators.