לוח שנה משולב

Spatial and temporal regulation of the apoptotic machinery is critical for the execution of multiple cellular events. Here we identify Seven In Absentia Homolog 3 (Siah3) as a new regulator of the cell death machinery during axonal pruning in developing mice. Sensory neurons from Siah3 KO mice exhibit delayed axonal degeneration and Caspase-3 activation in response to trophic deprivation. In agreement, the Siah3 KO mice display increased peripheral sensory innervation. Mechanistically, we show that Siah3 directly binds to the core mitophagy machinery protein Parkin, and, importantly, co-ablation of Prkn and Siah3 reverses the delay in axonal degeneration and Caspase-3 activation detected in Siah3 KO neurons. Strikingly, loss of Siah3 causes dramatic increase in axonal mitophagy upon trophic deprivation, suggesting that Siah3 is a positive regulator of axonal elimination acting by modulation of Parkin-mediated mitophagy. Overall, our results suggest that Parkin-mediated mitophagy restrains the apoptotic system by eliminating signaling mitochondria and reveal the role of mitochondrial signaling in axonal elimination.

When training large neural networks, there are typically many solutions that perfectly fit the training data. Nevertheless, gradient-based methods have a tendency to reach those which generalize well, and understanding this "implicit bias" has been a subject of extensive research. In this talk, I will discuss three works that show settings where the implicit bias provably implies generalization in two-layer neural networks: First, the implicit bias implies generalization in univariate ReLU networks. Second, in ReLU networks where the data consists of clusters and the correlations between cluster means are small, the implicit bias leads to solutions that generalize well, but are highly vulnerable to adversarial examples. Third, in Leaky-ReLU networks (as well as linear classifiers), under certain assumptions on the input distribution, the implicit bias leads to benign overfitting: the estimators interpolate noisy training data and simultaneously generalize well to test data.

Based on joint works with Spencer Frei, Itay Safran, Peter L. Bartlett, Jason D. Lee, and Nati Srebro.


Bio:
Gal is a postdoc at TTI-Chicago and the Hebrew University, hosted by Nati Srebro and Amit Daniely as part of the NSF/Simons Collaboration on the Theoretical Foundations of Deep Learning. Prior to that, he was a postdoc at the Weizmann Institute, hosted by Ohad Shamir, and a PhD student at the Hebrew University, advised by Orna Kupferman. His research focuses on theoretical machine learning, with an emphasis on deep-learning theory.

The intercalation of ions is a powerful strategy to modify the structural, electrical and optical properties of layered solids [1]. It is also a key ingredient for energy storage and the operation of secondary batteries. Even though first studies of driving chemical elements into the van der Waals galleries of graphite date back to as early as 1840, we believe that our recent successful demonstration of on-chip electrochemistry driven ion intercalation in the single van der Waals gallery of a graphene bilayer marks a paradigm shift. The “active” device area is left uncovered by the electrolyte and we can borrow the toolbox of the low dimensional electron system community for monitoring the ion transport [2,3]. This intercalation 2.0 offers, in conjunction with the versatile technique of van der Waals stacking of 2D materials for engineering arbitrary layered structures and hetero-interfaces, unprecedented control and truly unique opportunities to chart new territory in the fields addressing ion transport, diffusion, storage and intercalant induced structural, electronic and optical property changes. Here, examples will be presented how this technique has been exploited to study ion diffusion, ion ordering as well as unconventional superconductivity.
[1] M.S. Dresselhaus, G. Dresselhaus, Intercalation compounds of graphite, Advances in Physics 51-1, 1-186 (2002).
[2] M. Kühne, F. Paolucci, J. Popovic, P. Ostrovsky, J. Maier, J. Smet, Ultrafast lithium diffusion in bilayer graphene, Nature Nanotechnology 12, 895 (2017).
[3] M. Kühne, F. Börrnert, S. Fecher, M. Ghorbani-Asl, J. Biskupek, D. Samuelis, A. Krasheninnikov, U. Kaiser, J. Smet, Reversible superdense ordering of lithium between two graphene sheets, Nature 564, 234-239 (2018).

Membrane voltage in dendrites plays a key role in mediating synaptic integration and activity-dependent plasticity; but dendritic voltages have been difficult to measure.  We developed molecular, optical, and computational tools for simultaneous optogenetic perturbations and voltage mapping in dendrites of neurons in acute slices and in awake mice.  These experiments revealed relations between dendritic ion channel biophysics and rules of synaptic integration and plasticity.  I will also describe tools for mapping large-scale network dynamics with millisecond time resolution, and for mapping brain-wide patterns of plasticity.

TBA