Anticipation and negative group delay in a retina.

The mechanism of negative group delay (NGD) is used to understand the anticipatory capability of a retina. Experiments with retinas from bullfrogs are performed to compare with the predictions of the NGD model. In particular, whole field stochastic stimulations with various autocorrelation times are used to probe anticipatory responses from the retina. We find that the NGD model can reproduce essential features of experimental observations characterized by the cross correlations between the stimulation and the retinal responses. Experiments with dark light pulse stimulations further support the NGD mechanism, with the retina producing time-advanced pulse responses. However, no time-advanced pulse responses are produced by bright pulses. Counterintuitively, the NGD model shows that it is the delay in the system which gives rise to anticipation because of the negative feedback adaptation mechanism.

Characterization of Predictive Behavior of a Retina by Mutual Information.

Probing a bullfrog retina with spatially uniform light pulses of correlated stochastic intervals, we calculate the mutual information between the spiking output at the ganglion cells measured with multi-electrode array (MEA) and the interval of the stimulus at a time shift later. The time-integrated information from the output about the future stimulus is maximized when the mean interval of the stimulus is within the dynamic range of the well-established anticipative phenomena of omitted-stimulus responses for the retina. The peak position of the mutual information as a function of the time shift is typically negative considering the processing delay of the retina. However, the peak position can become positive for long enough correlation time of the stimulus when the pulse intervals are generated by a Hidden Markovian model (HMM). This is indicative of a predictive behavior of the retina which is possible only when the hidden variable of the HMM can be recovered from the history of the stimulus for a prediction of its future. We verify that stochastic intervals of the same mean, variance, and correlation time do not result in the same predictive behavior of the retina when they are generated by an Ornstein-Uhlenbeck (OU) process, which is strictly Markovian.

A High-Throughput Platform for Formulating and Screening Multifunctional Nanoparticles Capable of Simultaneous Delivery of Genes and Transcription Factors.

Simultaneous delivery of multiple genes and proteins (e.g., transcription factors; TFs) is an emerging issue surrounding therapeutic research due to their ability to regulate cellular circuitry. Current gene and protein delivery strategies, however, are based on slow batch synthesis, which is ineffective, poorly controlled, and incapable of simultaneous delivery of both genes and proteins with synergistic functions. Consequently, advances in this field have been limited to in vitro studies. Here, by integrating microfluidic technologies with a supramolecular synthetic strategy, we present a high-throughput approach for formulating and screening multifunctional supramolecular nanoparticles (MFSNPs) self-assembled from a collection of functional modules to achieve simultaneous delivery of one gene and TF with unprecedented efficiency both in vitro and in vivo. We envision that this new approach could open a new avenue for immunotherapy, stem cell reprogramming, and other therapeutic applications.