Boosting the Performance of Object Tracking with a Half-Precision Particle Filter on GPU

High-performance GPU-accelerated particle filter methods are critical for object detection applications, ranging from autonomous driving, robot localization, to time-series prediction. In this work, we investigate the design, development and optimization of particle-filter using half-precision on CUDA cores and compare their performance and accuracy with single- and double-precision baselines on Nvidia V100, A100, A40 and T4 GPUs. To mitigate numerical instability and precision losses, we introduce algorithmic changes in the particle filters. Using half-precision leads to a performance improvement of 1.5-2x and 2.5-4.6x with respect to single- and double-precision baselines respectively, at the cost of a relatively small loss of accuracy.Comment: 12 pages, 8 figures, conference. To be published in The 21st International Workshop on Algorithms, Models and Tools for Parallel Computing on Heterogeneous Platforms (HeteroPar2023

AMP-Activated Kinase Restricts Rift Valley Fever Virus Infection by Inhibiting Fatty Acid Synthesis

The cell intrinsic innate immune responses provide a first line of defense against viral infection, and often function by targeting cellular pathways usurped by the virus during infection. In particular, many viruses manipulate cellular lipids to form complex structures required for viral replication, many of which are dependent on de novo fatty acid synthesis. We found that the energy regulator AMPK, which potently inhibits fatty acid synthesis, restricts infection of the Bunyavirus, Rift Valley Fever Virus (RVFV), an important re-emerging arthropod-borne human pathogen for which there are no effective vaccines or therapeutics. We show restriction of RVFV both by AMPK and its upstream activator LKB1, indicating an antiviral role for this signaling pathway. Furthermore, we found that AMPK is activated during RVFV infection, leading to the phosphorylation and inhibition of acetyl-CoA carboxylase, the first rate-limiting enzyme in fatty acid synthesis. Activating AMPK pharmacologically both restricted infection and reduced lipid levels. This restriction could be bypassed by treatment with the fatty acid palmitate, demonstrating that AMPK restricts RVFV infection through its inhibition of fatty acid biosynthesis. Lastly, we found that this pathway plays a broad role in antiviral defense since additional viruses from disparate families were also restricted by AMPK and LKB1. Therefore, AMPK is an important component of the cell intrinsic immune response that restricts infection through a novel mechanism involving the inhibition of fatty acid metabolism

Advances in Cardiovascular Disease Lipid Research Can Provide Novel Insights Into Mycobacterial Pathogenesis

Cardiovascular disease (CVD) is the leading cause of death in industrialized nations and an emerging health problem in the developing world. Systemic inflammatory processes associated with alterations in lipid metabolism are a major contributing factor that mediates the development of CVDs, especially atherosclerosis. Therefore, the pathways promoting alterations in lipid metabolism and the interplay between varying cellular types, signaling agents, and effector molecules have been well-studied. Mycobacterial species are the causative agents of various infectious diseases in both humans and animals. Modulation of host lipid metabolism by mycobacteria plays a prominent role in its survival strategy within the host as well as in disease pathogenesis. However, there are still several knowledge gaps in the mechanistic understanding of how mycobacteria can alter host lipid metabolism. Considering the in-depth research available in the area of cardiovascular research, this review presents an overview of the parallel areas of research in host lipid-mediated immunological changes that might be extrapolated and explored to understand the underlying basis of mycobacterial pathogenesis

AMPK restricts RVFV infection.

<p><b>A.</b> Plaque assays were performed on wild type (WT) and AMPKα1/AMPKα2^−/− MEFs. Representative data from triplicate experiments is shown. <b>B.</b> Quantification of plaques from <b>A.</b> presented as the normalized mean±SD relative to the number of wild type plaques from three experiments. <b>C.</b> The diameter of 30 representative plaques in each duplicate well from <b>A.</b> was used to calculate the average plaque area, displayed as the normalized mean+SD in triplicate experiments. <b>D.</b> WT or AMPKα1/AMPKα2^−/− MEFs were infected with serial dilutions of RVFV, incubated for 16 hours, and processed for immunofluorescence. (RVFV-N, green; nuclei, blue). <b>E.</b> Quantification of <b>D.</b> presented as percent of infected cells. A representative of three experiments is shown. <b>F.</b> One-step growth curve of RVFV in WT or AMPKα1/AMPKα2^−/− MEFs. RVFV grown in WT or AMPKα1/AMPKα2^−/− MEFs for 4, 8, or 12 hours was tittered on BHK cells and is presented as the normalized mean of triplicate experiments ±SD. * indicates p<0.05.</p

AMPK restricts RVFV RNA replication.

<p><b>A.</b> Northern blot of genomic S segment and N mRNA from RVFV (MOI 1) grown in WT or AMPKα1/AMPKα2^−/− MEFs for 4, 8, or 12 hours. A representative of triplicate experiments is shown. <b>B–C.</b> Quantification of RVFV mRNA (<b>B</b>) or genomic RNA (<b>C</b>) in WT or AMPKα1/AMPKα2^−/− MEFs displayed as the normalized fold change from WT 4 hours. A representative of triplicate experiments is shown. <b>D.</b> RVFV binding assay. RVFV (MOI 10) was bound to WT or AMPKα1/AMPKα2^−/− MEFs at 4°C for 1 hour, then washed, and treated with PBS or trypsin to remove bound virus. qRTPCR was performed on isolated RNA to detect RVFV S genome. Data are displayed as the average ΔΔCT of triplicate experiments normalized to GAPDH control. * indicates p<0.05. <b>E.</b> 2DG (12 mM), A769662 (100 uM) or Ammonium Chloride (NH₄Cl, 12 mM) was added either 1 hour prior to infection with RVFV (MOI 1), with infection, or 1, 2, or 4 hours post infection. After 10 hours of infection cells were fixed and processed for immunofluorescence. Data are displayed as the average percent infection relative to the post entry level of infection (NH₄Cl added at 4 hpi) ± SD from triplicate experiments. * indicates p<0.05.</p

Additional arboviruses are restricted by AMPK.

<p>WT or AMPKα1/AMPKα2^−/− MEFs were infected with serial dilutions of KUNV (<b>A</b>), SINV (<b>E</b>), or VSV (<b>I</b>) and processed for immunofluorescence. (Virus, green; nuclei, blue). Quantifications of the percent infection for KUNV (<b>B</b>), SINV (<b>F</b>) and VSV (<b>J</b>) are shown as representatives of triplicate experiments. LKB1^−/−;LKB1 and LKB1^−/−;Vec MEFs were infected with serial dilutions of KUNV (<b>C</b>), SINV (<b>G</b>), and VSV (<b>K</b>) and processed for immunofluorescence. (Virus, green; nuclei, blue). Quantifications of the percent infection are shown for KUNV (<b>D</b>), SINV (<b>H</b>) and VSV (<b>L</b>) are shown as representatives of triplicate experiments.</p

Addition of palmitate restores RVFV infection in the presence of A769662.

<p><b>A.</b> U2OS cells were pretreated with 100 µM palmitate overnight and 100 µM A769662 or PBS was added 1 hour prior to infection with RVFV (MOI 1). Cells were incubated for 10 hours, and processed for immunofluorescence. (RVFV-N, green; nuclei, blue) <b>B.</b> Quantification of <b>A.</b> Data are displayed as the normalized percent infection relative to the untreated control at MOI 1.25±SD in triplicate experiments; * indicates p<0.05 compared to untreated vehicle control.</p

Acetyl-CoA Carboxylase Activity is Tightly Regulated by AMPK during RVFV Infection.

<p><b>A.</b> Phosphorylation of AMPK and downstream effectors upon RVFV infection. WT MEFs were infected with RVFV (MOI 1) for 4 or 8 hours. Lysates were collected and assayed by immunoblot for phospho-AMPK, phospho-ACC, and phospho-eEF2. Total protein was assayed for each and Tubulin was measured as a loading control. Representative blot of triplicate experiments is shown. <b>B.</b> Phosphorylation of AMPK and downstream effectors in WT and AMPKα1/AMPKα2^−/− MEFs. Cells were treated with AMPK activators 2DG (12 mM), oligomycin (OM, 10 µM), and A769662 (100 µM) for 4 hours. Lysates were collected and assayed by immunoblot as above. Representative blot of triplicate experiments shown. <b>C.</b> Phosphorylation of AMPK and ACC upon treatment with UV-inactivated RVFV. WT MEFs were infected with live or UV-inactivated RVFV (MOI 1) for 4 or 8 hours. Lysates were collected and assayed by immunoblot as above. Representative blot of triplicate experiments is shown. <b>D.</b> Blocking fatty acid synthesis inhibits RVFV infection. MEFs were treated with the fatty acid synthase inhibitors Cerulenin (45 pM) and C75 (12.5 µM) or the AMPK activator A769662 (100 µM), infected with RVFV (MOI 1), and processed for immunofluorescence. Data are displayed as the normalized average percent infection relative to the untreated control ± SD in triplicate experiments. * indicates p<0.05. <b>E.</b> WT MEFs were treated with 100 µM A769662 for 10 hours and stained for cellular lipids with BODIPY lipophilic fluorescent dye. (BODIPY, red; nuclei, blue). Representative images from triplicate experiments are shown. <b>F.</b> Quantification of <b>E.</b> presented as integrated BODIPY intensity per cell relative to untreated control ± SD in triplicate experiments. * indicates p<0.05. <b>G.</b> WT and AMPKα1/AMPKα2^−/− MEFs were grown overnight and stained for cellular lipids with BODIPY lipophilic fluorescent dye. (BODIPY, red; nuclei, blue). Representative images from triplicate experiments are shown. <b>H.</b> Quantification of <b>G.</b> presented as integrated BODIPY intensity per cell relative to WT ± SD in triplicate experiments. * indicates p<0.05.</p