Decoupling algorithms from schedules for easy optimization of image processing pipelines

Using existing programming tools, writing high-performance image processing code requires sacrificing readability, portability, and modularity. We argue that this is a consequence of conflating what computations define the algorithm, with decisions about storage and the order of computation. We refer to these latter two concerns as the schedule, including choices of tiling, fusion, recomputation vs. storage, vectorization, and parallelism. We propose a representation for feed-forward imaging pipelines that separates the algorithm from its schedule, enabling high-performance without sacrificing code clarity. This decoupling simplifies the algorithm specification: images and intermediate buffers become functions over an infinite integer domain, with no explicit storage or boundary conditions. Imaging pipelines are compositions of functions. Programmers separately specify scheduling strategies for the various functions composing the algorithm, which allows them to efficiently explore different optimizations without changing the algorithmic code. We demonstrate the power of this representation by expressing a range of recent image processing applications in an embedded domain specific language called Halide, and compiling them for ARM, x86, and GPUs. Our compiler targets SIMD units, multiple cores, and complex memory hierarchies. We demonstrate that it can handle algorithms such as a camera raw pipeline, the bilateral grid, fast local Laplacian filtering, and image segmentation. The algorithms expressed in our language are both shorter and faster than state-of-the-art implementations.National Science Foundation (U.S.) (Grant 0964004)National Science Foundation (U.S.) (Grant 0964218)National Science Foundation (U.S.) (Grant 0832997)United States. Dept. of Energy (Award DE-SC0005288)Cognex CorporationAdobe System

Head Impact Exposure in Youth and Collegiate American Football

The relationship between head impact and subsequent brain injury for American football players is not well defined, especially for youth. The objective of this study is to quantify and assess Head Impact Exposure (HIE) metrics among youth and collegiate football players. This multiseason study enrolled 639 unique athletes (354 collegiate; 285 youth, ages 9–14), recording 476,209 head impacts (367,337 collegiate; 108,872 youth) over 971 sessions (480 collegiate; 491 youth). Youth players experienced 43 and 65% fewer impacts per competition and practice, respectively, and lower impact magnitudes compared to collegiate players (95th percentile peak linear acceleration (PLA, g) competition: 45.6 vs 61.9; 95th percentile PLA practice: 42.6 vs 58.8; 95th percentile peak rotational acceleration (PRA, rad∙s–2) competition: 2262 vs 4422; 95th percentile PRA practice: 2081 vs 4052; 95th percentile HITsp competition: 25.4 vs 32.8; 95th percentile HITsp practice: 23.9 vs 30.2). Impacts during competition were more frequent and of greater magnitude than during practice at both levels. Quantified comparisons of head impact frequency and magnitude between youth and collegiate athletes reveal HIE differences as a function of age, and expanded insight better informs the development of age-appropriate guidelines for helmet design, prevention measures, standardized testing, brain injury diagnosis, and recovery management

An ultra-stable single-chain insulin analog resists thermal inactivation and exhibits biological signaling duration equivalent to the native protein

Thermal degradation of insulin complicates its delivery and use. Previous efforts to engineer ultra-stable analogs were confounded by prolonged cellular signaling in vivo, of unclear safety and complicating mealtime therapy. We therefore sought an ultra-stable analog whose potency and duration of action on intravenous bolus injection in diabetic rats are indistinguishable from wild-type (WT) insulin. Here, we describe the structure, function, and stability of such an analog, a 57-residue single-chain insulin (SCI) with multiple acidic substitutions. Cell-based studies revealed native-like signaling properties with negligible mitogenic activity. Its crystal structure, determined as a novel zinc-free hexamer at 2.8 Å, revealed a native insulin fold with incomplete or absent electron density in the C domain; complementary NMR studies are described in the accompanying article. The stability of the analog (ΔGU 5.0(±0.1) kcal/mol at 25 °C) was greater than that of WT insulin (3.3(±0.1) kcal/mol). On gentle agitation, the SCI retained full activity for >140 days at 45 °C and >48 h at 75 °C. These findings indicate that marked resistance to thermal inactivation in vitro is compatible with native duration of activity in vivo Further, whereas WT insulin forms large and heterogeneous aggregates above the standard 0.6 mm pharmaceutical strength, perturbing the pharmacokinetic properties of concentrated formulations, dynamic light scattering, and size-exclusion chromatography revealed only limited SCI self-assembly and aggregation in the concentration range 1-7 mm Such a combination of favorable biophysical and biological properties suggests that SCIs could provide a global therapeutic platform without a cold chain

Multi-ancestry study of blood lipid levels identifies four loci interacting with physical activity.

Many genetic loci affect circulating lipid levels, but it remains unknown whether lifestyle factors, such as physical activity, modify these genetic effects. To identify lipid loci interacting with physical activity, we performed genome-wide analyses of circulating HDL cholesterol, LDL cholesterol, and triglyceride levels in up to 120,979 individuals of European, African, Asian, Hispanic, and Brazilian ancestry, with follow-up of suggestive associations in an additional 131,012 individuals. We find four loci, in/near CLASP1, LHX1, SNTA1, and CNTNAP2, that are associated with circulating lipid levels through interaction with physical activity; higher levels of physical activity enhance the HDL cholesterol-increasing effects of the CLASP1, LHX1, and SNTA1 loci and attenuate the LDL cholesterol-increasing effect of the CNTNAP2 locus. The CLASP1, LHX1, and SNTA1 regions harbor genes linked to muscle function and lipid metabolism. Our results elucidate the role of physical activity interactions in the genetic contribution to blood lipid levels

Building a diverse workforce and thinkforce to reduce health disparities

The Research Centers in Minority Institutions (RCMI) Program was congressionally man-dated in 1985 to build research capacity at institutions that currently and historically recruit, train, and award doctorate degrees in the health professions and health-related sciences, primarily to individuals from underrepresented and minority populations. RCMI grantees share similar infrastructure needs and institutional goals. Of particular importance is the professional development of multidisciplinary teams of academic and community scholars (the “workforce”) and the harnessing of the heterogeneity of thought (the “thinkforce”) to reduce health disparities. The purpose of this report is to summarize the presentations and discussion at the RCMI Investigator Development Core (IDC) Workshop, held in conjunction with the RCMI Program National Conference in Bethesda, Maryland, in December 2019. The RCMI IDC Directors provided information about their professional development activities and Pilot Projects Programs and discussed barriers identified by new and early-stage investigators that limit effective career development, as well as potential solutions to overcome such obstacles. This report also proposes potential alignments of professional development activities, targeted goals and common metrics to track productivity and success

Automatically Harnessing Sparse Acceleration

Sparse linear algebra is central to many scientific programs, yet compilers fail to optimize it well. High-performance libraries are available, but adoption costs are significant. Moreover, libraries tie programs into vendor-specific software and hardware ecosystems, creating non-portable code. In this paper, we develop a new approach based on our specification Language for implementers of Linear Algebra Computations (LiLAC). Rather than requiring the application developer to (re)write every program for a given library, the burden is shifted to a one-off description by the library implementer. The LiLAC-enabled compiler uses this to insert appropriate library routines without source code changes. LiLAC provides automatic data marshaling, maintaining state between calls and minimizing data transfers. Appropriate places for library insertion are detected in compiler intermediate representation, independent of source languages. We evaluated on large-scale scientific applications written in FORTRAN; standard C/C++ and FORTRAN benchmarks; and C++ graph analytics kernels. Across heterogeneous platforms, applications and data sets we show speedups of 1.1$\times$ to over 10$\times$ without user intervention.Comment: Accepted to CC 202

The genomes of two key bumblebee species with primitive eusocial organization

Background: The shift from solitary to social behavior is one of the major evolutionary transitions. Primitively eusocial bumblebees are uniquely placed to illuminate the evolution of highly eusocial insect societies. Bumblebees are also invaluable natural and agricultural pollinators, and there is widespread concern over recent population declines in some species. High-quality genomic data will inform key aspects of bumblebee biology, including susceptibility to implicated population viability threats. Results: We report the high quality draft genome sequences of Bombus terrestris and Bombus impatiens, two ecologically dominant bumblebees and widely utilized study species. Comparing these new genomes to those of the highly eusocial honeybee Apis mellifera and other Hymenoptera, we identify deeply conserved similarities, as well as novelties key to the biology of these organisms. Some honeybee genome features thought to underpin advanced eusociality are also present in bumblebees, indicating an earlier evolution in the bee lineage. Xenobiotic detoxification and immune genes are similarly depauperate in bumblebees and honeybees, and multiple categories of genes linked to social organization, including development and behavior, show high conservation. Key differences identified include a bias in bumblebee chemoreception towards gustation from olfaction, and striking differences in microRNAs, potentially responsible for gene regulation underlying social and other traits. Conclusions: These two bumblebee genomes provide a foundation for post-genomic research on these key pollinators and insect societies. Overall, gene repertoires suggest that the route to advanced eusociality in bees was mediated by many small changes in many genes and processes, and not by notable expansion or depauperation

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN