7 research outputs found
In-Datacenter Performance Analysis of a Tensor Processing Unit
Many architects believe that major improvements in cost-energy-performance
must now come from domain-specific hardware. This paper evaluates a custom
ASIC---called a Tensor Processing Unit (TPU)---deployed in datacenters since
2015 that accelerates the inference phase of neural networks (NN). The heart of
the TPU is a 65,536 8-bit MAC matrix multiply unit that offers a peak
throughput of 92 TeraOps/second (TOPS) and a large (28 MiB) software-managed
on-chip memory. The TPU's deterministic execution model is a better match to
the 99th-percentile response-time requirement of our NN applications than are
the time-varying optimizations of CPUs and GPUs (caches, out-of-order
execution, multithreading, multiprocessing, prefetching, ...) that help average
throughput more than guaranteed latency. The lack of such features helps
explain why, despite having myriad MACs and a big memory, the TPU is relatively
small and low power. We compare the TPU to a server-class Intel Haswell CPU and
an Nvidia K80 GPU, which are contemporaries deployed in the same datacenters.
Our workload, written in the high-level TensorFlow framework, uses production
NN applications (MLPs, CNNs, and LSTMs) that represent 95% of our datacenters'
NN inference demand. Despite low utilization for some applications, the TPU is
on average about 15X - 30X faster than its contemporary GPU or CPU, with
TOPS/Watt about 30X - 80X higher. Moreover, using the GPU's GDDR5 memory in the
TPU would triple achieved TOPS and raise TOPS/Watt to nearly 70X the GPU and
200X the CPU.Comment: 17 pages, 11 figures, 8 tables. To appear at the 44th International
Symposium on Computer Architecture (ISCA), Toronto, Canada, June 24-28, 201
The circulating SARS-CoV-2 spike variant N439K maintains fitness while evading antibody-mediated immunity
SARS-CoV-2 can mutate to evade immunity, with consequences for the efficacy of emerging vaccines and antibody therapeutics. Herein we demonstrate that the immunodominant SARS-CoV-2 spike (S) receptor binding motif (RBM) is the most divergent region of S, and provide epidemiological, clinical, and molecular characterization of a prevalent RBM variant, N439K. We demonstrate that N439K S protein has enhanced binding affinity to the hACE2 receptor, and that N439K virus has similar clinical outcomes and in vitro replication fitness as compared to wild- type. We observed that the N439K mutation resulted in immune escape from a panel of neutralizing monoclonal antibodies, including one in clinical trials, as well as from polyclonal sera from a sizeable fraction of persons recovered from infection. Immune evasion mutations that maintain virulence and fitness such as N439K can emerge within SARS-CoV-2 S, highlighting the need for ongoing molecular surveillance to guide development and usage of vaccines and therapeutics
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Circulating SARS-CoV-2 spike N439K variants maintain fitness while evading antibody-mediated immunity.
SARS-CoV-2 can mutate and evade immunity, with consequences for efficacy of emerging vaccines and antibody therapeutics. Here, we demonstrate that the immunodominant SARS-CoV-2 spike (S) receptor binding motif (RBM) is a highly variable region of S and provide epidemiological, clinical, and molecular characterization of a prevalent, sentinel RBM mutation, N439K. We demonstrate N439K S protein has enhanced binding affinity to the hACE2 receptor, and N439K viruses have similar in vitro replication fitness and cause infections with similar clinical outcomes as compared to wild type. We show the N439K mutation confers resistance against several neutralizing monoclonal antibodies, including one authorized for emergency use by the US Food and Drug Administration (FDA), and reduces the activity of some polyclonal sera from persons recovered from infection. Immune evasion mutations that maintain virulence and fitness such as N439K can emerge within SARS-CoV-2 S, highlighting the need for ongoing molecular surveillance to guide development and usage of vaccines and therapeutics
Circulating SARS-CoV-2 spike N439K variants maintain fitness while evading antibody-mediated immunity.
SARS-CoV-2 can mutate and evade immunity, with consequences for efficacy of emerging vaccines and antibody therapeutics. Here, we demonstrate that the immunodominant SARS-CoV-2 spike (S) receptor binding motif (RBM) is a highly variable region of S and provide epidemiological, clinical, and molecular characterization of a prevalent, sentinel RBM mutation, N439K. We demonstrate N439K S protein has enhanced binding affinity to the hACE2 receptor, and N439K viruses have similar in vitro replication fitness and cause infections with similar clinical outcomes as compared to wild type. We show the N439K mutation confers resistance against several neutralizing monoclonal antibodies, including one authorized for emergency use by the US Food and Drug Administration (FDA), and reduces the activity of some polyclonal sera from persons recovered from infection. Immune evasion mutations that maintain virulence and fitness such as N439K can emerge within SARS-CoV-2 S, highlighting the need for ongoing molecular surveillance to guide development and usage of vaccines and therapeutics.COG-UK is supported by funding from the Medical Research Council (MRC) part of UK Research & Innovation (UKRI), the National Institute of Health Research (NIHR) and Genome Research Limited, operating as the Wellcome Sanger Institute