AMPA receptor and synaptic plasticity

Long-term changes in synaptic strength, such as long-term potentiation (LTP) and long-term depression (LTD), have been proposed to be the cellular correlates of learning and memory formation. In the hippocampus, an area of the brain associated with memory formation, LTP and LTD require functional modification of AMPA receptors (AMPARs). Since AMPARs are the major ionotropic glutamate receptors in the brain, changing the single channel properties and/or the number at synapses can greatly affect excitatory synaptic function. Recent studies highlight that functional recruitment of Ca2+-permeable AMPARs (CP-AMPARs) at synapses is another key regulatory mechanism that alter excitatory synaptic transmission. By combining electrophysiology, biochemistry, and imaging methods, I found that phosphorylation of the GluR1 subunit of AMPAR on the serine-845 site (GluR1-S845) is critical for the functional recruitment of CP-AMPARs. This has functional consequences as CP-AMPARs can be expressed at synapses by various neuronal activities both in vitro and in vivo, such as by LTP, sensory experiences, brain diseases and drug addiction. On the other hand, dephosphorylation of the GluR1-S845 is necessary for producing long-term synaptic depression, which is accompanied by a loss in functional CP-AMPARs. Interestingly, the GluR1-S845 site is not required for the plasticity of dendritic spine structures, which is considered an important mechanism for long-term synaptic plasticity as well as learning and memory formation. These results suggest that the functional change in synaptic transmission and the structural synaptic plasticity may utilize separate signaling cascades. In a parallel study, I demonstrated that the beta-site cleaving enzyme 1 (BACE1), which cleaves the amyloid precursor protein (APP) to release the amyloid beta peptide (Abeta), is also involved in regulating synaptic plasticity. Using mice lacking the BACE1 gene, I found that BACE1 is involved in specific forms of synaptic plasticity as well as presynaptic function. Abnormal accumulation of Abeta by excessive BACE1 activity is thought responsible for triggering the pathology of Alzheimer's disease (AD). However, my results caution the development of AD therapeutics targeting the BACE1 activity. In summary, my studies demonstrate that the function of AMPA receptors can be regulated in multiple ways, including phosphorylation of a single amino acid, and is critically involved in synaptic plasticity that underlies learning and memory formation

Adversarial Auto-Augment with Label Preservation: A Representation Learning Principle Guided Approach

Data augmentation is a critical contributing factor to the success of deep learning but heavily relies on prior domain knowledge which is not always available. Recent works on automatic data augmentation learn a policy to form a sequence of augmentation operations, which are still pre-defined and restricted to limited options. In this paper, we show that a prior-free autonomous data augmentation's objective can be derived from a representation learning principle that aims to preserve the minimum sufficient information of the labels. Given an example, the objective aims at creating a distant "hard positive example" as the augmentation, while still preserving the original label. We then propose a practical surrogate to the objective that can be optimized efficiently and integrated seamlessly into existing methods for a broad class of machine learning tasks, e.g., supervised, semi-supervised, and noisy-label learning. Unlike previous works, our method does not require training an extra generative model but instead leverages the intermediate layer representations of the end-task model for generating data augmentations. In experiments, we show that our method consistently brings non-trivial improvements to the three aforementioned learning tasks from both efficiency and final performance, either or not combined with strong pre-defined augmentations, e.g., on medical images when domain knowledge is unavailable and the existing augmentation techniques perform poorly. Code is available at: https://github.com/kai-wen-yang/LPA3}{https://github.com/kai-wen-yang/LPA3.Comment: 36th Conference on Neural Information Processing Systems (NeurIPS 2022

Passive SSH Key Compromise via Lattices

We demonstrate that a passive network attacker can opportunistically obtain private RSA host keys from an SSH server that experiences a naturally arising fault during signature computation. In prior work, this was not believed to be possible for the SSH protocol because the signature included information like the shared Diffie-Hellman secret that would not be available to a passive network observer. We show that for the signature parameters commonly in use for SSH, there is an efficient lattice attack to recover the private key in case of a signature fault. We provide a security analysis of the SSH, IKEv1, and IKEv2 protocols in this scenario, and use our attack to discover hundreds of compromised keys in the wild from several independently vulnerable implementations

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Dynamic mechanical behaviors of Fangshan marble

Dynamic strength parameters are extensively used in mining engineering and rock mechanics. However, there are no widely accepted dynamic failure models for rocks. In this study, the dynamic punching shear strength, uniaxial compressive strength (UCS) and tensile strength of fine-grained Fangshan marble (FM) are first measured by using a split Hopkinson pressure bar (SHPB) system. The pulse-shaping technique is then implemented to maintain the dynamic force balance in SHPB tests. Experimental results show that the dynamic punching shear strength, UCS and tensile strength increase with the loading rate. A recently developed dynamic Mohr-Coulomb theory is then used to interpret the testing data. In this model, the angle of internal friction ϕ is assumed to be independent of loading rate and is obtained using the static strength values. According to the dynamic Mohr-Coulomb theory, the dynamic UCS and the dynamic tensile strength are predicted from the dynamic punching shear strength. Furthermore, based on this dynamic theory, the dynamic UCS is predicted from the dynamic tensile strength. The consistency between the predicted and measured dynamic strengths demonstrates that the dynamic Mohr-Coulomb theory is applicable to FM