A5049065304- DNA Repair Mechanisms
- Ubiquitin and proteasome pathways
- Genetics and Neurodevelopmental Disorders
- Machine Learning and Data Classification
- Microtubule and mitosis dynamics
- Fungal and yeast genetics research
- Autophagy in Disease and Therapy
- Neural Networks and Applications
- Genomics and Chromatin Dynamics
- Mass Spectrometry Techniques and Applications
- CRISPR and Genetic Engineering
- Melanoma and MAPK Pathways
- Advanced Proteomics Techniques and Applications
- Monoclonal and Polyclonal Antibodies Research
- Image Processing Techniques and Applications
- Gestational Diabetes Research and Management
- Protein Degradation and Inhibitors
- Cell Image Analysis Techniques
- Evolutionary Algorithms and Applications
- Protein Kinase Regulation and GTPase Signaling
- Adversarial Robustness in Machine Learning
- Scientific Computing and Data Management
- Distributed and Parallel Computing Systems
- Protein Tyrosine Phosphatases
- demographic modeling and climate adaptation
Cognizant (United States)
2023
University of California, San Diego
2010-2022
National Institute of Allergy and Infectious Diseases
2018-2020
Ludwig Cancer Research
2010-2019
Government of the United States of America
2018
Sentient Science (United States)
2018
The University of Texas at Austin
2018
University of Washington
2014
Ludwig Cancer Research
2014
University of California System
2010
The DNA damage checkpoint, consisting of an evolutionarily conserved protein kinase cascade, controls the response in eukaryotes. Knowledge vivo substrates checkpoint kinases is essential toward understanding their functions. Here we used quantitative mass spectrometry to identify 53 new and 34 previously known targets Mec1/Tel1, Rad53, Dun1 Saccharomyces cerevisiae. Analysis replication A (RPA)-associated proteins reveals extensive physical interactions between RPA-associated...
Mutations in C9orf72 leading to hexanucleotide expansions are the most common genetic causes for amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). A phenotype resembling ALS FTD is seen transgenic mice overexpressing expansions, but absent C9orf72-deficient mice. Thus, exact function of neurons how loss may contribute neuronal dysfunction remains be clearly defined. Here, we showed that primary hippocampal cultured from c9orf72 knockout have reduced dendritic...
Interhomolog crossovers promote proper chromosome segregation during meiosis and are formed by the regulated repair of programmed double-strand breaks. This regulation requires components synaptonemal complex (SC), a proteinaceous structure between homologous chromosomes. In yeast, SC formation "ZMM" genes, which encode functionally diverse set proteins, including transverse filament protein, Zip1. wild-type meiosis, Zmm proteins biased resolution recombination intermediates into that...
KRAS, which is mutated in ∼30% of all cancers, activates the RAF-MEK-ERK signaling cascade. CRAF required for growth KRAS mutant lung tumors, but requirement kinase activity unknown. Here, we show that subsets tumors are dependent on growth. Kinase-dead not dimer-defective rescues inhibition, suggesting dimerization required. Quantitative proteomics demonstrates increased levels CRAF:ARAF dimers cells, and depletion both ARAF CRAF-loss phenotype. Mechanistically, causes sustained ERK...
Saccharomyces cerevisiae Sae2 and its ortholog CtIP in higher eukaryotes have a conserved role the initial processing of DNA lesions influencing their subsequent repair pathways. is phosphorylated by ATR/ATM family kinases Mec1 Tel1 response to damage. Among Mec1/Tel1 consensus phosphorylation sites Sae2, we found that mutations Thr-90 Thr-279 into alanine caused persistent Rad53 activation transient damage, similar loss Sae2. To gain insight function this performed quantitative proteomics...
Small ubiquitin-like modifier (SUMO) E3 ligases are known to have a major role in preventing gross chromosomal rearrangements (GCRs); however, relatively little is about the of SUMO isopeptidases genome maintenance and their controlling intracellular sumoylation homeostasis. Here we show isopeptidase Ulp2 Saccharomyces cerevisiae does not prevent accumulation GCRs, interestingly, its loss causes subunit-specific changes sumoylated minichromosome (MCM) helicase addition drastic nucleolar RENT...
In this paper, we provide a deep dive into the deployment of inference accelerators at Facebook. Many our ML workloads have unique characteristics, such as sparse memory accesses, large model sizes, well high compute, and network bandwidth requirements. We co-designed high-performance, energy-efficient accelerator platform based on these describe ecosystem developed deployed Facebook: both hardware, through Open Compute Platform (OCP), software framework tooling, Pytorch/Caffe2/Glow. A...
Mms21, a subunit of the Smc5/6 complex, possesses an E3 ligase activity for Small Ubiquitin-like MOdifier (SUMO). Here we show that mms21-CH mutation, which inactivates Mms21 activity, causes increased accumulation gross chromosomal rearrangements (GCRs) selected in dGCR assay. These dGCRs are formed by non-allelic homologous recombination between divergent DNA sequences mediated Rad52-, Rrm3- and Pol32-dependent break-induced replication. Combining with sgs1Δ caused synergistic increase...
Quantitative proteomics has been widely used to elucidate many cellular processes. In particular, stable isotope labeling by amino acids in cell culture (SILAC) instrumental improving the quality of data generated from quantitative high-throughput proteomic studies. SILAC uses cell's natural metabolic pathways label proteins with isotopically heavy acids. Incorporation these effectively labels a proteome, allowing comparison cultures treated under different conditions. successfully applied...
We present our development experience and recent results for the MLPerf Tiny Inference Benchmark on field-programmable gate array (FPGA) platforms. use open-source hls4ml FINN workflows, which aim to democratize AI-hardware codesign of optimized neural networks FPGAs. design implementation process keyword spotting, anomaly detection, image classification benchmark tasks. The resulting hardware implementations are quantized, configurable, spatial dataflow architectures tailored speed...
Explanation techniques that synthesize small, interpretable changes to a given image while producing desired in the model prediction have become popular for introspecting black-box models. Commonly referred as counterfactuals, synthesized explanations are required contain discernible (for easy interpretability) also being realistic (consistency data manifold). In this paper, we focus on case where access only trained deep classifier and not actual training data. While problem of inverting...
The success of deep learning depends on finding an architecture to fit the task. As has scaled up more challenging tasks, architectures have become difficult design by hand. This paper proposes automated method, CoDeepNEAT, for optimizing through evolution. By extending existing neuroevolution methods topology, components, and hyperparameters, this method achieves results comparable best human designs in standard benchmarks object recognition language modeling. It also supports building a...
In order to preserve genome integrity, extrinsic or intrinsic DNA damages must be repaired before they accumulate in cells and trigger other mutations rearrangements. Eukaryotic are able respond different genotoxic stresses as well single double strand breaks (DSBs), suggesting highly sensitive robust mechanisms detect lesions that a signal transduction cascade which, turn, controls the damage response (DDR). Furthermore, distinguish natural chromosomal ends from DSBs prevent inappropriate...
Abstract Mms21, a subunit of the Smc5/6 complex, possesses an E3 ligase activity for Small Ubiquitin-like MOdifier (SUMO), which has major, but poorly understood role in genome maintenance. Here we show mutations that inactivate Mms21 cause Rad52- and Pol32-dependent break-induced replication (BIR), specifically requires Rrm3 DNA helicase. Interestingly, affecting both Sgs1 helicase, not sumoylation Sgs1, further accumulation rearrangements, indicating distinct roles suppressing...
ABSTRACT Objectives We developed and evaluated a privacy-preserving O ne-shot D istributed A lgorithm to fit multi-center C ox proportional hazard model ( ODAC ) without sharing patient-level information across sites. Methods Using data from single site combined with only aggregated other sites, we constructed surrogate likelihood function, approximating the Cox partial function obtained using all By maximizing each local estimate of parameter, estimator was as weighted average estimates....
Inflammation response in exercise of healthy humans is significantly different than that which commonly reported for chronic inflammatory conditions. Regardless the scenario, cytokines such as Tumor Necrosis Factor (TNF)-α and Interleukin (IL)-1b have demonstrated pro-inflammatory functions, while IL-6 has versatile pro- anti-inflammatory roles when a factor. Prolonged skeletal muscle contractions sufficient intensity been shown to induce significant protein damage complex cascade involving...
Glyburide (Gly) is routinely used to treat hyperglycemia during pregnancy. Our objective was determine if maternal‐fetal disposition of Gly and metabolites dependent on gestational age in pregnant mice because similar studies cannot be done humans. Following retro‐orbital injection Gly, maternal plasma fetuses were collected at 0.5‐240 min after dosing. Pharmacokinetic parameters determined using a pseudo‐profile based bootstrap approach compartmental/noncompartmental analyses. Maternal...
Genome instability often characterizes many cancers and is indicative of high frequency mutations genome rearrangements. Several pathways, including the DNA damage checkpoint, play a role in maintaining stability by suppressing gross chromosomal rearrangements (GCRs). Additionally, eukaryotic genomes contain numerous repetitive sequences, segmental duplications regions copy number variation, which influence outcomes Using genetic assay Saccharomyces cerevisiae to screen for suppressors GCRs,...
Background: Epidemiology of acute febrile illness, a common cause hospitalization in Indonesia, has not been systematically studied. Methods. Prospective observational study patients >1 year age with temperature >38°C was conducted from July 2013 - June 2016. Patients received hospital standard-of-care (SOC). A reference laboratory performed molecular and serological testing. Clinical data, specimens for additional testing were collected at enrolment, days 14-28, three months. Follow up...