Search for: All records

In this paper, we address the challenges of asynchronous gradient descent in distributed learning environments, particularly focusing on addressing the challenges of stale gradients and the need for extensive communication resources. We develop a novel communication efficient framework that incorporates a gradient evaluation algorithm to assess and utilize delayed gradients based on their quality, ensuring efficient and effective model updates while significantly reducing communication overhead. Our proposed algorithm requires agents to only send the norm of the gradients rather than the computed gradient. The server then decides whether to accept the gradient if the ratio between the norm of the gradient and the distance between the global model parameter and the local model parameter exceeds a certain threshold. With the proper choice of the threshold, we show that the convergence rate achieves the same order as the synchronous stochastic gradient without depending on the staleness value unlike most of the existing works. Given the computational complexity of the initial algorithm, we introduce a simplified variant that prioritizes the practical applicability without compromising on the convergence rates. Our simulations demonstrate that our proposed algorithms outperform existing state-of-the-art methods, offering improved convergence rates, stability, accuracy, and resource consumption. 

Serum tyrosine and phenylalanine levels increase during aging and age-associated disorders. We previously showed that tyrosyl-tRNA synthetase (TyrRS/YARS1) is reduced in Alzheimer's Disease (AD) brains, and tyrosine and phenylalanine decrease TyrRS in neurons. Here, we found that tau is a negative regulator, whereas estrogen and leucine act as positive regulators of TyrRS. Young female mice exhibit increased TyrRS in the cortex compared to male mice. Notably, young Tau knockout male, but not female mice showed increased cortical TyrRS. Tau accumulation in middle-aged female mice did not decrease cortical TyrRS compared to males, suggesting that middle aged females are resilient to tau-mediated TyrRS depletion. Tyrosine and phenylalanine treatment decreased tubulin tyrosination, activated DNA repair pathways, and protected against etoposide (ETO) and camptothecin (CPT)-induced toxicity, respectively, in neurons. While tyrosine facilitated topoisomerase 1 (TOP1) recruitment to chromatin and inhibited global transcription, in contrast, phenylalanine recruited topoisomerase 2 beta (TOP2β) to chromatin and stimulated global transcription. Furthermore, tyrosine decreased the presence of DNA fragments in a comet assay whereas phenylalanine increased them. Addition of cis-resveratrol (cis-RSV) protected against tyrosine-induced transcription inhibition by facilitating the recruitment of both TOP1 and TOP2β to chromatin and increasing tubulin tyrosination. Moreover, cis-RSV decreased both total and phosphorylated tau and protected neurons against amyloid beta (Aβ)-induced neurite degeneration and DNA damage. Gene expression profiling using human embryonic stem cell (hESC)-derived neurons demonstrated that cis-RSV is a broad-spectrum neuroprotective and anti-viral agent. In contrast, trans-RSV mimics phenylalanine-induced gene expression, including downregulation of long genes and induction of an AD-like gene expression signature. This work suggests that age and disease-associated increases in serum tyrosine and phenylalanine levels would activate neuronal DNA repair while inhibiting transcription and tubulin tyrosination. cis-RSV protects against their toxicity by restoring tubulin tyrosination, TOP1 and TOP2β-mediated transcription, and decreasing tau in primary neurons.