Dynamic estimation of epidemiological parameters of COVID-19 outbreak and effects of interventions on its spread

Background: A key challenge in estimating epidemiological parameters for a pandemic such as the initial COVID-19 outbreak in Wuhan is the discrepancy between the officially reported number of infections and the true number of infections. A common approach to tackling the challenge is to use the number of infections exported from the originating city to infer the true number. This approach can only provide a static estimate of the epidemiological parameters before city lockdown because there are almost no exported cases thereafter.Methods: We propose a Bayesian estimation method that dynamically estimates the epidemiological parameters by recovering true numbers of infections from day-to-day official numbers. To illustrate the use of this method, we provide a comprehensive retrospection on how the COVID-19 had progressed in Wuhan from January 19 to March 5, 2020. Particularly, we estimate that the outbreak sizes by January 23 and March 5 were 11,239 [95% CI 4,794–22,372] and 124,506 [95% CI 69,526–265,113], respectively.Results: The effective reproduction number attained its maximum on January 24 (3.42 [95% CI 3.34–3.50]) and became less than 1 from February 7 (0.76 [95% CI 0.65–0.92]). We also estimate the effects of two major government interventions on the spread of COVID-19 in Wuhan.Conclusions: This case study by our proposed method affirms the believed importance and effectiveness of imposing tight non-essential travel restrictions and affirm the importance and effectiveness of government interventions (e.g., transportation suspension and large scale hospitalization) for effective mitigation of COVID-19 community spread

Fast Prototyping Next-Generation Accelerators for New ML Models using MASE: ML Accelerator System Exploration

Machine learning (ML) accelerators have been studied and used extensively to compute ML models with high performance and low power. However, designing such accelerators normally takes a long time and requires significant effort. Unfortunately, the pace of development of ML software models is much faster than the accelerator design cycle, leading to frequent and drastic modifications in the model architecture, thus rendering many accelerators obsolete. Existing design tools and frameworks can provide quick accelerator prototyping, but only for a limited range of models that can fit into a single hardware device, such as an FPGA. Furthermore, with the emergence of large language models, such as GPT-3, there is an increased need for hardware prototyping of these large models within a many-accelerator system to ensure the hardware can scale with the ever-growing model sizes. In this paper, we propose an efficient and scalable approach for exploring accelerator systems to compute large ML models. We developed a tool named MASE that can directly map large ML models onto an efficient streaming accelerator system. Over a set of ML models, we show that MASE can achieve better energy efficiency to GPUs when computing inference for recent transformer models. Our tool will open-sourced upon publication

Metabolic Profiling Reveals a Dependency of Human Metastatic Breast Cancer on Mitochondrial Serine and One-Carbon Unit Metabolism.

Breast cancer is the most common cancer among American women and a major cause of mortality. To identify metabolic pathways as potential targets to treat metastatic breast cancer, we performed metabolomics profiling on the breast cancer cell line MDA-MB-231 and its tissue-tropic metastatic subclones. Here, we report that these subclones with increased metastatic potential display an altered metabolic profile compared with the parental population. In particular, the mitochondrial serine and one-carbon (1C) unit pathway is upregulated in metastatic subclones. Mechanistically, the mitochondrial serine and 1C unit pathway drives the faster proliferation of subclones through enhanced de novo purine biosynthesis. Inhibition of the first rate-limiting enzyme of the mitochondrial serine and 1C unit pathway, serine hydroxymethyltransferase (SHMT2), potently suppresses proliferation of metastatic subclones in culture and impairs growth of lung metastatic subclones at both primary and metastatic sites in mice. Some human breast cancers exhibit a significant association between the expression of genes in the mitochondrial serine and 1C unit pathway with disease outcome and higher expression of SHMT2 in metastatic tumor tissue compared with primary tumors. In addition to breast cancer, a few other cancer types, such as adrenocortical carcinoma and kidney chromophobe cell carcinoma, also display increased SHMT2 expression during disease progression. Together, these results suggest that mitochondrial serine and 1C unit metabolism plays an important role in promoting cancer progression, particularly in late-stage cancer. IMPLICATIONS: This study identifies mitochondrial serine and 1C unit metabolism as an important pathway during the progression of a subset of human breast cancers

Cancer-associated mesothelial cells promote ovarian cancer chemoresistance through paracrine osteopontin signaling

Ovarian cancer is the leading cause of gynecological malignancy-related deaths, due to its widespread intraperitoneal metastases and acquired chemoresistance. Mesothelial cells are an important cellular component of the ovarian cancer microenvironment that promote metastasis. However, their role in chemoresistance is unclear. Here, we investigated whether cancer-associated mesothelial cells promote ovarian cancer chemoresistance and stemness in vitro and in vivo. We found that osteopontin is a key secreted factor that drives mesothelial-mediated ovarian cancer chemoresistance and stemness. Osteopontin is a secreted glycoprotein that is clinically associated with poor prognosis and chemoresistance in ovarian cancer. Mechanistically, ovarian cancer cells induced osteopontin expression and secretion by mesothelial cells through TGF-β signaling. Osteopontin facilitated ovarian cancer cell chemoresistance via the activation of the CD44 receptor, PI3K/AKT signaling, and ABC drug efflux transporter activity. Importantly, therapeutic inhibition of osteopontin markedly improved the efficacy of cisplatin in both human and mouse ovarian tumor xenografts. Collectively, our results highlight mesothelial cells as a key driver of ovarian cancer chemoresistance and suggest that therapeutic targeting of osteopontin may be an effective strategy for enhancing platinum sensitivity in ovarian cancer

Repulsive guidance molecule B inhibits metastasis and is associated with decreased mortality in non-small cell lung cancer

Repulsive guidance molecules (RGMs) are co-receptors of bone morphogenetic proteins (BMPs) and programmed death ligand 2 (PD-L2), and might be involved in lung and other cancers. We evaluated repulsive guidance molecule B (RGMB) expression in 165 non-small cell lung cancer (NSCLC) tumors and 22 normal lung tissue samples, and validated the results in an independent series of 131 samples. RGMB was downregulated in NSCLC (P ≤ 0.001), possibly through promoter hypermethylation. Reduced RGMB expression was observed in advanced-stage tumors (P = 0.017) and in tumors with vascular invasion (P < 0.01), and was significantly associated with poor overall survival (39 vs. 62 months, P < 0.001) and with disease-associated patient mortality (P = 0.015). RGMB knockdown promoted cell adhesion, invasion and migration, in both NSCLC cell lines and an in vivo mouse model, which enhanced metastatic potential. Conversely, RGMB overexpression and secretion suppressed cancer progression. The tumor-suppressing effect of RGMB was exerted through inhibition of the Smad1/5/8 pathway. Our results demonstrate that RGMB is an important inhibitor of NSCLC metastasis and that low RGMB expression is a novel predictor or a poor prognosis

PyPose v0.6: The Imperative Programming Interface for Robotics

PyPose is an open-source library for robot learning. It combines a learning-based approach with physics-based optimization, which enables seamless end-to-end robot learning. It has been used in many tasks due to its meticulously designed application programming interface (API) and efficient implementation. From its initial launch in early 2022, PyPose has experienced significant enhancements, incorporating a wide variety of new features into its platform. To satisfy the growing demand for understanding and utilizing the library and reduce the learning curve of new users, we present the fundamental design principle of the imperative programming interface, and showcase the flexible usage of diverse functionalities and modules using an extremely simple Dubins car example. We also demonstrate that the PyPose can be easily used to navigate a real quadruped robot with a few lines of code

An atlas of DNA methylomes in porcine adipose and muscle tissues

It is evident that epigenetic factors, especially DNA methylation, have essential roles in obesity development. Here, using pig as a model, we investigate the systematic association between DNA methylation and obesity. We sample eight variant adipose and two distinct skeletal muscle tissues from three pig breeds living within comparable environments but displaying distinct fat level. We generate 1,381 Gb of sequence data from 180 methylated DNA immunoprecipitation libraries, and provide a genome-wide DNA methylation map as well as a gene expression map for adipose and muscle studies. The analysis shows global similarity and difference among breeds, sexes and anatomic locations, and identifies the differentially methylated regions. The differentially methylated regions in promoters are highly associated with obesity development via expression repression of both known obesity-related genes and novel genes. This comprehensive map provides a solid basis for exploring epigenetic mechanisms of adipose deposition and muscle growth

Loss of Angiopoietin-like 7 diminishes the regeneration capacity of hematopoietic stem and progenitor cells

© 2015 Xiao et al.; licensee Biomed Central. Successful expansion of hematopoietic stem cells (HSCs) would benefit the use of HSC transplants in the clinic. Angiopoietin-like 7 promotes the expansion of hematopoietic stem and progenitor cells (HSPC) in vitro and ex vivo. However, the impact of loss of Angptl7 on HSPCs in vivo has not been characterized. Here, we generated Angptl7-deficient mice by TALEN-mediated gene targeting and found that HSC compartments in Angptl7-null mice were compromised. In addition, wild type (WT) HSPCs failed to repopulate in the BM of Angptl7-null mice after serial transplantations while the engraftment of Angptl7-deficient HSPCs in WT mice was not impaired. These results suggest that Angptl7 is required for HSPCs repopulation in a non-cell autonomous manner.Link_to_subscribed_fulltex

The dynamic evolution of multipoint interplanetary coronal mass ejections observed with BepiColombo, Tianwen-1, and MAVEN

We present two multipoint interplanetary coronal mass ejections (ICMEs) detected by the Tianwen-1 and Mars Atmosphere and Volatile Evolution spacecraft at Mars and the BepiColombo (0.56 au ∼0.67 au) upstream of Mars from 2021 December 5 to 31. This is the first time that BepiColombo is used as an upstream solar wind monitor ahead of Mars and that Tianwen-1 is used to investigate the magnetic field characteristics of ICMEs at Mars. The Heliospheric Upwind Extrapolation time model was used to connect the multiple in situ observations and the coronagraph observations from STEREO/SECCHI and SOHO/LASCO. The first fast coronal mass ejection event (∼761.2 km s−1), which erupted on December 4, impacted Mars centrally and grazed BepiColombo by its western flank. The ambient slow solar wind decelerated the west flank of the ICME, implying that the ICME event was significantly distorted by the solar wind structure. The second slow ICME event (∼390.7 km s−1) underwent an acceleration from its eruption to a distance within 0.69 au and then traveled with the constant velocity of the ambient solar wind. These findings highlight the importance of background solar wind in determining the interplanetary evolution and global morphology of ICMEs up to Mars distance. Observations from multiple locations are invaluable for space weather studies at Mars and merit more exploration in the future