Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), previously known as 2019 novel coronavirus (2019-nCoV), has spread rapidly across the globe, creating an unparalleled global health burden and spurring a deepening economic crisis. As of July 7th, 2020, almost seven months into the outbreak, there are no approved vaccines and few treatments available. Developing drugs that target multiple points in the viral life cycle could serve as a strategy to tackle the current as well as future coronavirus pandemics. Here we leverage the power of our recently developed in silico screening platform, VirtualFlow, to identify inhibitors that target SARS-CoV-2. VirtualFlow is able to efficiently harness the power of computing clusters and cloud-based computing platforms to carry out ultra-large scale virtual screens. In this unprecedented structure-based multi-target virtual screening campaign, we have used VirtualFlow to screen an average of approximately 1 billion molecules against each of 40 different target sites on 17 different potential viral and host targets in the cloud. In addition to targeting the active sites of viral enzymes, we also target critical auxiliary sites such as functionally important protein-protein interaction interfaces. This multi-target approach not only increases the likelihood of finding a potent inhibitor, but could also help identify a collection of anti-coronavirus drugs that would retain efficacy in the face of viral mutation. Drugs belonging to different regimen classes could be combined to develop possible combination therapies, and top hits that bind at highly conserved sites would be potential candidates for further development as coronavirus drugs. Here, we present the top 200 in silico hits for each target site. While in-house experimental validation of some of these compounds is currently underway, we want to make this array of potential inhibitor candidates available to researchers worldwide in consideration of the pressing need for fast-tracked drug development.

The COVID-19 pandemic continues to pose a substantial threat to human lives and is likely to do so for years to come. Despite the availability of vaccines, searching for efficient small-molecule drugs that are widely available, including in low- and middle-income countries, is an ongoing challenge. In this work, we report the results of a community effort, the “Billion molecules against Covid-19 challenge”, to identify small-molecule inhibitors against SARS-CoV-2 or relevant human receptors. Participating teams used a wide variety of computational methods to screen a minimum of 1 billion virtual molecules against 6 protein targets. Overall, 31 teams participated, and they suggested a total of 639,024 potentially active molecules, which were subsequently ranked to find ‘consensus compounds’. The organizing team coordinated with various contract research organizations (CROs) and collaborating institutions to synthesize and test 878 compounds for activity against proteases (Nsp5, Nsp3, TMPRSS2), nucleocapsid N, RdRP (Nsp12 domain), and (alpha) spike protein S. Overall, 27 potential inhibitors were experimentally confirmed by binding-, cleavage-, and/or viral suppression assays and are presented here. All results are freely available and can be taken further downstream without IP restrictions. Overall, we show the effectiveness of computational techniques, community efforts, and communication across research fields (i.e., protein expression and crystallography, in silico modeling, synthesis and biological assays) to accelerate the early phases of drug discovery.

The COVID‐19 pandemic continues to pose a substantial threat to human lives and is likely to do so for years to come. Despite the availability of vaccines, searching for efficient small‐molecule drugs that are widely available, including in low‐ and middle‐income countries, is an ongoing challenge. In this work, we report the results of an open science community effort, the “Billion molecules against COVID‐19 challenge”, to identify small‐molecule inhibitors against SARS‐CoV‐2 or relevant human receptors. Participating teams used a wide variety of computational methods to screen a minimum of 1 billion virtual molecules against 6 protein targets. Overall, 31 teams participated, and they suggested a total of 639,024 molecules, which were subsequently ranked to find ‘consensus compounds’. The organizing team coordinated with various contract research organizations (CROs) and collaborating institutions to synthesize and test 878 compounds for biological activity against proteases (Nsp5, Nsp3, TMPRSS2), nucleocapsid N, RdRP (only the Nsp12 domain), and (alpha) spike protein S. Overall, 27 compounds with weak inhibition/binding were experimentally identified by binding‐, cleavage‐, and/or viral suppression assays and are presented here. Open science approaches such as the one presented here contribute to the knowledge base of future drug discovery efforts in finding better SARS‐CoV‐2 treatments.

The unparalleled global effort to combat the continuing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic over the last year has resulted in promising prophylactic measures. However, a need still exists for cheap, effective therapeutics, and targeting multiple points in the viral life cycle could help tackle the current, as well as future, coronaviruses. Here, we leverage our recently developed, ultra-large-scale in silico screening platform, VirtualFlow, to search for inhibitors that target SARS-CoV-2. In this unprecedented structure-based virtual campaign, we screened roughly 1 billion molecules against each of 40 different target sites on 17 different potential viral and host targets. In addition to targeting the active sites of viral enzymes, we also targeted critical auxiliary sites such as functionally important protein-protein interactions.

A Kavli foundation sponsored workshop on the theme \emph{Petabytes to Science} was held 12$^{th}$ to 14$^{th}$ of February 2019 in Las Vegas. The aim of the this workshop was to discuss important trends and technologies which may support astronomy. We also tackled how to better shape the workforce for the new trends and how we should approach education and public outreach. This document was coauthored during the workshop and edited in the weeks after. It comprises the discussions and highlights many recommendations which came out of the workshop. We shall distill parts of this document and formulate potential white papers for the decadal survey.

The field of astronomy has arrived at a turning point in terms of size and complexity of both datasets and scientific collaboration. Commensurately, algorithms and statistical models have begun to adapt — e.g., via the onset of artificial intelligence — which itself presents new challenges and opportunities for growth. This white paper aims to offer guidance and ideas for how we can evolve our technical and collaborative frameworks to promote efficient algorithmic development and take advantage of opportunities for scientific discovery in the petabyte era. We discuss challenges for discovery in large and complex data sets; challenges and requirements for the next stage of development of statistical methodologies and algorithmic tool sets; how we might change our paradigms of collaboration and education; and the ethical implications of scientists’ contributions to widely applicable algorithms and computational modeling. We start with six distinct recommendations that are supported by the commentary following them. This white paper is related to a larger corpus of effort that has taken place within and around the Petabytes to Science Workshops (https://petabytestoscience.github.io/; Bauer et al. 2019). 1. STRATEGIC PLAN: RECOMMENDATIONS REC-1: Create funding models, opportunities, and programs to support the development of advanced algorithms and statistical methods specifically targeted to the astronomy domain. Area: Analysis. Audience: Agency, Astronomer. Time Frame: Medium The increasingly large and complex datasets resulting from a new generation of telescopes, satellites, and experiments require the development of sophisticated and robust algorithms and methodologies. These techniques must have statistically rigorous underpinnings, as well as being adaptable to changes in computer architectures. It is also critical to fund the long-term maintenance, curation, and distribution of these algorithms. REC-2: Build automated discovery engines. Area: Analysis. Audience: Technologist, Astronomer. Time Frame: Long New hypotheses are difficult to generate in an era of large and complex datasets. Frameworks that can detect outliers or new patterns (and reliably minimize false-positive) within our data could address many of the needs of current and planned science experiments. Funding and developing these engines as a community would lead to broad access to the tools needed for scientific exploration. REC-3: Promote interdisciplinary collaboration between fields, and industry. Area: Analysis. Audience: Agency, Manager, Astronomer. Time Frame: Long Expertise across multiple domains is required to tailor algorithmic solutions to astronomical challenges. The astronomical community should more heavily and directly engage researchers from industry and non-astronomy fields in the development and optimization of algorithms and statistical methods. Agencies and academic departments should develop

We present a response to the 2018 Request for Information (RFI) from the NITRD, NCO, NSF regarding the "Update to the 2016 National Artificial Intelligence Research and Development Strategic Plan." Through this document, we provide a response to the question of whether and how the National Artificial Intelligence Research and Development Strategic Plan (NAIRDSP) should be updated from the perspective of Fermilab, America's premier national laboratory for High Energy Physics (HEP). We believe the NAIRDSP should be extended in light of the rapid pace of development and innovation in the field of Artificial Intelligence (AI) since 2016, and present our recommendations below. AI has profoundly impacted many areas of human life, promising to dramatically reshape society --- e.g., economy, education, science --- in the coming years. We are still early in this process. It is critical to invest now in this technology to ensure it is safe and deployed ethically. Science and society both have a strong need for accuracy, efficiency, transparency, and accountability in algorithms, making investments in scientific AI particularly valuable. Thus far the US has been a leader in AI technologies, and we believe as a national Laboratory it is crucial to help maintain and extend this leadership. Moreover, investments in AI will be important for maintaining US leadership in the physical sciences.

Software is critical to astronomical research. Sharing and sustaining astronomical software has long-term impacts on scientific outcomes. However, support for this has been uneven, creating significant risks. Thus, we highlight changes that will enable a sustainable software sharing system for astronomy and astrophysics in the next decade.

The field of astronomy has arrived at a turning point in terms of size and complexity of both datasets and scientific collaboration. Commensurately, algorithms and statistical models have begun to adapt --- e.g., via the onset of artificial intelligence --- which itself presents new challenges and opportunities for growth. This white paper aims to offer guidance and ideas for how we can evolve our technical and collaborative frameworks to promote efficient algorithmic development and take advantage of opportunities for scientific discovery in the petabyte era. We discuss challenges for discovery in large and complex data sets; challenges and requirements for the next stage of development of statistical methodologies and algorithmic tool sets; how we might change our paradigms of collaboration and education; and the ethical implications of scientists' contributions to widely applicable algorithms and computational modeling. We start with six distinct recommendations that are supported by the commentary following them. This white paper is related to a larger corpus of effort that has taken place within and around the Petabytes to Science Workshops (https://petabytestoscience.github.io/).

With the volume of Earth observation data expanding rapidly, cloud computing is quickly changing the way these data are processed, analyzed, and visualized. Collocating freely available Earth observation data on a cloud computing infrastructure may create opportunities unforeseen by the original data provider for innovation and value-added data re-use, but existing systems at data centers are not designed for supporting requests for large data transfers. A lack of common methodology necessitates that each data center handle such requests from different cloud vendors differently. Guidelines are needed to support enabling all cloud vendors to utilize a common methodology for bulk-downloading data from data centers, thus preventing the providers from building custom capabilities to meet the needs of individual vendors. This paper presents recommendations distilled from use cases provided by three cloud vendors (Amazon, Google, and Microsoft) and are based on the vendors' interactions with data systems at different Federal agencies and organizations. These specific recommendations range from obvious steps for improving data usability (such as ensuring the use of standard data formats and commonly supported projections) to non-obvious undertakings important for enabling bulk data downloads at scale. These recommendations can be used to evaluate and improve existing data systems for high-volume data transfers, and their adoption can lead to cloud vendors utilizing a common methodology.

In this paper, we describe how to leverage cloud resources to generate large-scale mosaics of the galactic plane in multiple wavelengths. Our goal is to generate a 16-wavelength infrared Atlas of the Galactic Plane at a common spatial sampling of 1 arcsec, processed so that they appear to have been measured with a single instrument. This will be achieved by using the Montage image mosaic engine process observations from the 2MASS, GLIMPSE, MIPSGAL, MSX and WISE datasets, over a wavelength range of 1 mu m to 24 mu m, and by using the Pegasus Workflow Management System for managing the workload. When complete, the Atlas will be made available to the community as a data product.We are generating images that cover +/- 180 degrees in Galactic longitude and +/- 20 degrees in Galactic latitude, to the extent permitted by the spatial coverage of each dataset. Each image will be 5 degrees x5 degrees in size (including an overlap of 1 degrees with neighboring tiles), resulting in an atlas of 1,001 images. The final size will be about 50 TBs.This paper will focus on the computational challenges, solutions, and lessons learned in producing the Atlas. To manage the computation we are using the Pegasus Workflow Management System, a mature, highly fault-tolerant system now in release 4.2.2 that has found wide applicability across many science disciplines. A scientific workflow describes the dependencies between the tasks and in most cases the workflow is described as a directed acyclic graph, where the nodes are tasks and the edges denote the task dependencies. A defining property for a scientific workflow is that it manages data flow between tasks. Applied to the galactic plane project, each 5 by 5 mosaic is a Pegasus workflow. Pegasus is used to fetch the source images, execute the image mosaicking steps of Montage, and store the final outputs in a storage system.As these workflows are very I/O intensive, care has to be taken when choosing what infrastructure to execute the workflow on. In our setup, we choose to use dynamically provisioned compute clusters running on the Amazon Elastic Compute Cloud (EC2). All our instances are using the same base image, which is configured to come up as a master node by default. The master node is a central instance from where the workflow can be managed. Additional worker instances are provisioned and configured to accept work assignments from the master node. The system allows for adding/removing workers in an ad hoc fashion, and could be run in large configurations.To-date we have performed 245,000 CPU hours of computing and generated 7,029 images and metadata totaling 30 TB. With the current set up our runtime would be 340,000 CPU hours for the whole project. Using spot m2.4xlarge instances, the cost would be approximately $5,950. Using faster AWS instances, such as cc2.8xlarge could potentially decrease the total CPU hours and further reduce the compute costs. The paper will explore these tradeoffs.

The NASA Exoplanet Science Institute (NExScI) hosts the annual Sagan Workshops, thematic meetings aimed at introducing researchers to the latest tools and methodologies in exoplanet research. The theme of the Summer 2012 workshop, held from July 23 to July 27 at Caltech, was to explore the use of exoplanet light curves to study planetary system architectures and atmospheres. A major part of the workshop was to use hands-on sessions to instruct attendees in the use of three open source tools for the analysis of light curves, especially from the Kepler mission. Each hands-on session involved the 160 attendees using their laptops to follow step-by-step tutorials given by experts. We describe how we used the Amazon Elastic Cloud 2 to run these applications.

This paper describes by example how astronomers can use cloud-computing resources offered by Amazon Web Services (AWS) to create new datasets at scale. We have created from existing surveys an atlas of the Galactic Plane at 16 wavelengths from 1 {\mu}m to 24 {\mu}m with pixels co-registered at spatial sampling of 1 arcsec. We explain how open source tools support management and operation of a virtual cluster on AWS platforms to process data at scale, and describe the technical issues that users will need to consider, such as optimization of resources, resource costs, and management of virtual machine instances.

NASA's vision is to “reach for new heights and reveal the unknown so that what we do and learn will benefit all humankind.” While our missions provide large volumes of unique and invaluable data to the scientific community, they also serve to inspire and educate the next generation of engineers and scientists. One critical aspect of “benefiting all humankind” is to make our missions as visible and accessible as possible to facilitate the transfer of scientific knowledge to the public. The recent successful landing of the Curiosity rover on Mars exemplified this vision: we shared the landing event via live video streaming and web experiences with millions of people around the world. The video stream on Curiosity's website was delivered by a highly scalable stack of computing resources in the cloud to cache and distribute the video stream to our viewers. While this work was done in the context of public outreach, it has extensive implications for the development of mission critical, highly available, and elastic applications in the cloud for a diverse set of use cases across NASA.

As the VLSI/ULSI device density is increasing common failure mechanisms, such as internal latch-up phenomenon in sea-of-gate ASIC devices, are surfacing and becoming an important reliability issue. The traditional latch-up phenomenon sensitivity assessment techniques are no longer adequate; because the phenomenon is not limited to causes externally induced at the device peripherals but in process-induced defects as well. Therefore, an understanding of this effect is critical to both manufacturing and engineering communities. The purpose of this paper is to report a study of latch-ups in sea-of-gate (continuous arrays) ASIC devices. Two techniques, traditional and laser-induced testings, are presented.