Investment Management Code of Conduct for Endowments, Foundations, and Charitable Organizations

The Investment Management Code of Conduct for Endowments, Foundations, and Charitable Organizations represents best practice for the oversight of an entity's financial assets. Governing Body members should uphold the general principles of the Code in the management of the assets and the organization

Decoupled Sampling for Real-Time Graphics Pipelines

We propose decoupled sampling, an approach that decouples shading from visibility sampling in order to enable motion blur and depth-of-field at reduced cost. More generally, it enables extensions of modern real-time graphics pipelines that provide controllable shading rates to trade off quality for performance. It can be thought of as a generalization of GPU-style multisample antialiasing (MSAA) to support unpredictable shading rates, with arbitrary mappings from visibility to shading samples as introduced by motion blur, depth-of-field, and adaptive shading. It is inspired by the Reyes architecture in offline rendering, but targets real-time pipelines by driving shading from visibility samples as in GPUs, and removes the need for micropolygon dicing or rasterization. Decoupled Sampling works by defining a many-to-one hash from visibility to shading samples, and using a buffer to memoize shading samples and exploit reuse across visibility samples. We present extensions of two modern GPU pipelines to support decoupled sampling: a GPU-style sort-last fragment architecture, and a Larrabee-style sort-middle pipeline. We study the architectural implications and derive end-to-end performance estimates on real applications through an instrumented functional simulator. We demonstrate high-quality motion blur and depth-of-field, as well as variable and adaptive shading rates

Decoupled Sampling for Graphics Pipelines

We propose a generalized approach to decoupling shading from visibility sampling in graphics pipelines, which we call decoupled sampling. Decoupled sampling enables stochastic supersampling of motion and defocus blur at reduced shading cost, as well as controllable or adaptive shading rates which trade off shading quality for performance. It can be thought of as a generalization of multisample antialiasing (MSAA) to support complex and dynamic mappings from visibility to shading samples, as introduced by motion and defocus blur and adaptive shading. It works by defining a many-to-one hash from visibility to shading samples, and using a buffer to memoize shading samples and exploit reuse across visibility samples. Decoupled sampling is inspired by the Reyes rendering architecture, but like traditional graphics pipelines, it shades fragments rather than micropolygon vertices, decoupling shading from the geometry sampling rate. Also unlike Reyes, decoupled sampling only shades fragments after precise computation of visibility, reducing overshading. We present extensions of two modern graphics pipelines to support decoupled sampling: a GPU-style sort-last fragment architecture, and a Larrabee-style sort-middle pipeline. We study the architectural implications of decoupled sampling and blur, and derive end-to-end performance estimates on real applications through an instrumented functional simulator. We demonstrate high-quality motion and defocus blur, as well as variable and adaptive shading rates

Lunar Lander Offloading Operations Using a Heavy-Lift Lunar Surface Manipulator System

This study investigates the feasibility of using a heavy-lift variant of the Lunar Surface Manipulator System (LSMS-H) to lift and handle a 12 metric ton payload. Design challenges and requirements particular to handling heavy cargo were examined. Differences between the previously developed first-generation LSMS and the heavy-lift version are highlighted. An in-depth evaluation of the tip-over risk during LSMS-H operations has been conducted using the Synergistic Engineering Environment and potential methods to mitigate that risk are identified. The study investigated three specific offloading scenarios pertinent to current Lunar Campaign studies. The first involved offloading a large element, such as a habitat or logistics module, onto a mobility chassis with a lander-mounted LSMS-H and offloading that payload from the chassis onto the lunar surface with a surface-mounted LSMS-H. The second scenario involved offloading small pressurized rovers with a lander-mounted LSMS-H. The third scenario involved offloading cargo from a third-party lander, such as the proposed ESA cargo lander, with a chassis-mounted LSMS-H. In all cases, the analyses show that the LSMS-H can perform the required operations safely. However, Chariot-mounted operations require the addition of stabilizing outriggers, and when operating from the Lunar surface, LSMS-H functionality is enhanced by adding a simple ground anchoring system

Filovirus RefSeq Entries: Evaluation and Selection of Filovirus Type Variants, Type Sequences, and Names

Sequence determination of complete or coding-complete genomes of viruses is becoming common practice for supporting the work of epidemiologists, ecologists, virologists, and taxonomists. Sequencing duration and costs are rapidly decreasing, sequencing hardware is under modification for use by non-experts, and software is constantly being improved to simplify sequence data management and analysis. Thus, analysis of virus disease outbreaks on the molecular level is now feasible, including characterization of the evolution of individual virus populations in single patients over time. The increasing accumulation of sequencing data creates a management problem for the curators of commonly used sequence databases and an entry retrieval problem for end users. Therefore, utilizing the data to their fullest potential will require setting nomenclature and annotation standards for virus isolates and associated genomic sequences. The National Center for Biotechnology Information’s (NCBI’s) RefSeq is a non-redundant, curated database for reference (or type) nucleotide sequence records that supplies source data to numerous other databases. Building on recently proposed templates for filovirus variant naming [ ()////-], we report consensus decisions from a majority of past and currently active filovirus experts on the eight filovirus type variants and isolates to be represented in RefSeq, their final designations, and their associated sequences

The Science Performance of JWST as Characterized in Commissioning

This paper characterizes the actual science performance of the James Webb Space Telescope (JWST), as determined from the six month commissioning period. We summarize the performance of the spacecraft, telescope, science instruments, and ground system, with an emphasis on differences from pre-launch expectations. Commissioning has made clear that JWST is fully capable of achieving the discoveries for which it was built. Moreover, almost across the board, the science performance of JWST is better than expected; in most cases, JWST will go deeper faster than expected. The telescope and instrument suite have demonstrated the sensitivity, stability, image quality, and spectral range that are necessary to transform our understanding of the cosmos through observations spanning from near-earth asteroids to the most distant galaxies.Comment: 5th version as accepted to PASP; 31 pages, 18 figures; https://iopscience.iop.org/article/10.1088/1538-3873/acb29

The James Webb Space Telescope Mission

Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least $4m$. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the $6.5m$ James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 years, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space Telescope Overview, 29 pages, 4 figure

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Inhibition of key DNA double strand break repair protein kinases enhances radiosensitivity of head and neck cancer cells to X-ray and proton irradiation

Ionising radiation (IR) is widely used in cancer treatment, including for head and neck squamous cell carcinoma (HNSCC), where it induces significant DNA damage leading ultimately to tumour cell death. Among these lesions, DNA double strand breaks (DSBs) are the most threatening lesion to cell survival. The two main repair mechanisms that detect and repair DSBs are non-homologous end joining (NHEJ) and homologous recombination (HR). Among these pathways, the protein kinases ataxia telangiectasia mutated (ATM), ataxia telangiectasia and Rad3-related (ATR) and the DNA dependent protein kinase catalytic subunit (DNA-Pkcs) play key roles in the sensing of the DSB and subsequent coordination of the downstream repair events. Consequently, targeting these kinases with potent and specific inhibitors is considered an approach to enhance the radiosensitivity of tumour cells. Here, we have investigated the impact of inhibition of ATM, ATR and DNA-Pkcs on the survival and growth of six radioresistant HPV-negative HNSCC cell lines in combination with either X-ray irradiation or proton beam therapy, and confirmed the mechanistic pathway leading to cell radiosensitisation. Using inhibitors targeting ATM (AZD1390), ATR (AZD6738) and DNA-Pkcs (AZD7648), we observed that this led to significantly decreased clonogenic survival of HNSCC cell lines following both X-ray and proton irradiation. Radiosensitisation of HNSCC cells grown as 3D spheroids was also observed, particularly following ATM and DNA-Pkcs inhibition. We confirmed that the inhibitors in combination with X-rays and protons led to DSB persistence, and increased micronuclei formation. Cumulatively, our data suggest that targeting DSB repair, particularly via ATM and DNA-Pkcs inhibition, can exacerbate the impact of ionising radiation in sensitising HNSCC cell models.</p