Multi-Fidelity Active Learning with GFlowNets

In the last decades, the capacity to generate large amounts of data in science and engineering applications has been growing steadily. Meanwhile, the progress in machine learning has turned it into a suitable tool to process and utilise the available data. Nonetheless, many relevant scientific and engineering problems present challenges where current machine learning methods cannot yet efficiently leverage the available data and resources. For example, in scientific discovery, we are often faced with the problem of exploring very large, high-dimensional spaces, where querying a high fidelity, black-box objective function is very expensive. Progress in machine learning methods that can efficiently tackle such problems would help accelerate currently crucial areas such as drug and materials discovery. In this paper, we propose the use of GFlowNets for multi-fidelity active learning, where multiple approximations of the black-box function are available at lower fidelity and cost. GFlowNets are recently proposed methods for amortised probabilistic inference that have proven efficient for exploring large, high-dimensional spaces and can hence be practical in the multi-fidelity setting too. Here, we describe our algorithm for multi-fidelity active learning with GFlowNets and evaluate its performance in both well-studied synthetic tasks and practically relevant applications of molecular discovery. Our results show that multi-fidelity active learning with GFlowNets can efficiently leverage the availability of multiple oracles with different costs and fidelities to accelerate scientific discovery and engineering design.Comment: Code: https://github.com/nikita-0209/mf-al-gf

Green Planet Architecture - A Methodology for Self-Sustainable Distributed Renewable Energy Ecosystems

Our planet has been endowed with a host of natural mechanisms to keep the environment and climate in balance. Humans are now facing the need to restore this balance that has been upset in the past years because of a growing population and resource demands. To steer dependency away from freshwater crops and decrease environmental damage from humanity s fuel and energy demands, it is necessary to take advantage of the natural adaptive biomass resources that are already in place. Using methods of Green Planet Architecture, based on compilations of current research and procedures, could lead to new forms of energy and fueling as well as new sources for food and feed. Green Planet Architecture involves climatic adaptive biomass; geospatial intelligence; agri- and aqua-culture life cycles; and soil, wetland, and shoreline restoration. Plants such as Salicornia, seashore mallow, castor, mangroves, and perhaps Moringa can be modified (natural, model-assisted, or genetically modified) to thrive in salt-water and brackish water or otherwise not arable conditions, making them potentially new crops that will not displace traditional farming. These fueling sources also have potential to be used in other rapid-growth industries, such as the aviation industry, that have incentive to move towards more sustainable fuel supplies. This paper highlights an example of how synergistic development of biomass resources and geospatial intelligence high-performance computing capabilities can be focused to resolve potential drought-famine problems. These techniques, provide a basis for future e-science-based discovery (and access) through technology that can be expanded to support global societal applications

High fat diet alters gut microbiota but not spatial working memory in early middle-aged Sprague Dawley rats

As the global population ages, and rates of dementia rise, understanding lifestyle factors that play a role in the development and acceleration of cognitive decline is vital to creating therapies and recommendations to improve quality of later life. Obesity has been shown to increase risk for dementia. However, the specific mechanisms for obesity-induced cognitive decline remain unclear. One potential contributor to diet-induced cognitive changes is neuroinflammation. Furthermore, a source of diet-induced inflammation to potentially increase neuroinflammation is via gut dysbiosis. We hypothesized that a high fat diet would cause gut microbe dysbiosis, and subsequently: neuroinflammation and cognitive decline. Using 7-month old male Sprague Dawley rats, this study examined whether 8 weeks on a high fat diet could impact performance on the water radial arm maze, gut microbe diversity and abundance, and microgliosis. We found that a high fat diet altered gut microbe populations compared to a low fat, control diet. However, we did not observe any significant differences between dietary groups on maze performance (a measure of spatial working memory) or microgliosis. Our data reveal a significant change to the gut microbiome without subsequent effects to neuroinflammation (as measured by microglia characterization and counts in the cortex, hippocampus, and hypothalamus) or cognitive performance under the parameters of our study. However, future studies that explore duration of the diet, composition of the diet, age of animal model, and strain of animal model, must be explored

A machine learning framework for quantifying chemical segregation and microstructural features in atom probe tomography data

Atom probe tomography (APT) is ideally suited to characterize and understand the interplay of chemical segregation and microstructure in modern multicomponent materials. Yet, the quantitative analysis typically relies on human expertise to define regions of interest. We introduce a computationally efficient, multistage machine learning strategy to identify chemically distinct domains in a semi automated way, and subsequently quantify their geometric and compositional characteristics. In our algorithmic pipeline, we first coarse grain the APT data into voxels, collect the composition statistics, and decompose it via clustering in composition space. The composition classification then enables the real space segmentation via a density based clustering algorithm, thus revealing the microstructure at voxel resolution. Our approach is demonstrated for a Sm(Co,Fe)ZrCu alloy. The alloy exhibits two precipitate phases with a plate-like, but intertwined morphology. The primary segmentation is further refined to disentangle these geometrically complex precipitates into individual plate like parts by an unsupervised approach based on principle component analysis, or a U-Net based semantic segmentation trained on the former. Following the chemical and geometric analysis, detailed chemical distribution and segregation effects relative to the predominant plate-like geometry can be readily mapped without resorting to the initial voxelization

Alternate-Fueled Combustion-Sector Emissions

In order to meet rapidly growing demand for fuel, as well as address environmental concerns, the aviation industry has been testing alternate fuels for performance and technical usability in commercial and military aircraft. Currently, alternate aviation fuels must satisfy MIL-DTL- 83133F(2008) (military) or ASTM D 7566- Annex(2011) (commercial) standards and are termed drop-in fuel replacements. Fuel blends of up to 50% alternative fuel blended with petroleum (JP-8), which have become a practical alternative, are individually certified on the market. In order to make alternate fuels (and blends) a viable option for aviation, the fuel must be able to perform at a similar or higher level than traditional petroleum fuel. They also attempt to curb harmful emissions, and therefore a truly effective alternate fuel would emit at or under the level of currently used fuel. This paper analyzes data from gaseous and particulate emissions of an aircraft combustor sector. The data were evaluated at various inlet conditions, including variation in pressure and temperature, fuel-to-air ratios, and percent composition of alternate fuel. Traditional JP-8+100 data were taken as a baseline, and blends of JP- 8+100 with synthetic-paraffinic-kerosene (SPK) fuel (Fischer-Tropsch (FT)) were used for comparison. Gaseous and particulate emissions, as well as flame luminosity, were assessed for differences between FT composition of 0%, 50%, and 100%. The data showed that SPK fuel (a FT-derived fuel) had slightly lower harmful gaseous emissions, and smoke number information corroborated the hypothesis that SPK-FT fuels are cleaner burning fuels

Alternate-Fueled Combustor-Sector Emissions

In order to meet rapidly growing demand for fuel, as well as address environmental concerns, the aviation industry has been testing alternate fuels for performance and technical usability in commercial and military aircraft. In order to make alternate fuels (and blends) a viable option for aviation, the fuel must be able to perform at a similar or higher level than traditional petroleum fuel. They also attempt to curb harmful emissions, and therefore a truly effective alternate fuel would emit at or under the level of currently used fuel. This report analyzes data from gaseous and particulate emissions of an aircraft combustor sector. The data were evaluated at various inlet conditions, including variation in pressure and temperature, fuel-to-air ratios, and percent composition of alternate fuel. Traditional JP-8+100 data were taken as a baseline, and blends of JP-8+100 with synthetic-paraffinic-kerosene (SPK) fuel (Fischer-Tropsch (FT)) were used for comparison. Gaseous and particulate emissions, as well as flame luminosity, were assessed for differences between FT composition of 0, 50, and 100 percent. The data show that SPK fuel (an FT-derived fuel) had slightly lower harmful gaseous emissions, and smoke number information corroborated the hypothesis that SPK-FT fuels are cleaner burning fuels

Alternate-Fueled Combustor-Sector Performance

In order to realize alternative fueling for military and commercial use, the industry has set forth guidelines that must be met by each fuel. These aviation fueling requirements are outlined in MILDTL- 83133F(2008) or ASTM D 7566 Annex (2011) standards, and are classified as drop-in fuel replacements. This paper provides combustor performance data for synthetic-paraffinic-kerosene- (SPK-) type (Fisher-Tropsch (FT)) fuel and blends with JP-8+100, relative to JP-8+100 as baseline fueling. Data were taken at various nominal inlet conditions: 75 psia (0.52 MPa) at 500 F (533 K), 125 psia (0.86 MPa) at 625 F (603 K), 175 psia (1.21 MPa) at 725 F (658 K), and 225 psia (1.55 MPa) at 790 F (694 K). Combustor performance analysis assessments were made for the change in flame temperatures, combustor efficiency, wall temperatures, and exhaust plane temperatures at 3%, 4%, and 5% combustor pressure drop (% delta P) for fuel: air ratios (F/A) ranging from 0.010 to 0.025. Significant general trends show lower liner temperatures and higher flame and combustor outlet temperatures with increases in FT fueling relative to JP-8+100 fueling. The latter affects both turbine efficiency and blade/vane life

Deciphering the origin and therapeutic targets of cancer of unknown primary: a case report that illustrates the power of integrative whole-exome and transcriptome sequencing analysis

Cancer of unknown primary (CUP) represents a significant diagnostic and therapeutic challenge, being the third to fourth leading cause of cancer death, despite advances in diagnostic tools. This article presents a successful approach using a novel genomic analysis in the evaluation and treatment of a CUP patient, leveraging whole-exome sequencing (WES) and RNA sequencing (RNA-seq). The patient, with a history of multiple primary tumors including urothelial cancer, exhibited a history of rapid progression on empirical chemotherapy. The application of our approach identified a molecular target, characterized the tumor expression profile and the tumor microenvironment, and analyzed the origin of the tumor, leading to a tailored treatment. This resulted in a substantial radiological response across all metastatic sites and the predicted primary site of the tumor. We argue that a comprehensive genomic and molecular profiling approach, like the BostonGene© Tumor Portrait, can provide a more definitive, personalized treatment strategy, overcoming the limitations of current predictive assays. This approach offers a potential solution to an unmet clinical need for a standardized approach in identifying the tumor origin for the effective management of CUP

Measuring routine childhood vaccination coverage in 204 countries and territories, 1980-2019 : a systematic analysis for the Global Burden of Disease Study 2020, Release 1

Background Measuring routine childhood vaccination is crucial to inform global vaccine policies and programme implementation, and to track progress towards targets set by the Global Vaccine Action Plan (GVAP) and Immunization Agenda 2030. Robust estimates of routine vaccine coverage are needed to identify past successes and persistent vulnerabilities. Drawing from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2020, Release 1, we did a systematic analysis of global, regional, and national vaccine coverage trends using a statistical framework, by vaccine and over time. Methods For this analysis we collated 55 326 country-specific, cohort-specific, year-specific, vaccine-specific, and dosespecific observations of routine childhood vaccination coverage between 1980 and 2019. Using spatiotemporal Gaussian process regression, we produced location-specific and year-specific estimates of 11 routine childhood vaccine coverage indicators for 204 countries and territories from 1980 to 2019, adjusting for biases in countryreported data and reflecting reported stockouts and supply disruptions. We analysed global and regional trends in coverage and numbers of zero-dose children (defined as those who never received a diphtheria-tetanus-pertussis [DTP] vaccine dose), progress towards GVAP targets, and the relationship between vaccine coverage and sociodemographic development. Findings By 2019, global coverage of third-dose DTP (DTP3; 81.6% [95% uncertainty interval 80.4-82 .7]) more than doubled from levels estimated in 1980 (39.9% [37.5-42.1]), as did global coverage of the first-dose measles-containing vaccine (MCV1; from 38.5% [35.4-41.3] in 1980 to 83.6% [82.3-84.8] in 2019). Third- dose polio vaccine (Pol3) coverage also increased, from 42.6% (41.4-44.1) in 1980 to 79.8% (78.4-81.1) in 2019, and global coverage of newer vaccines increased rapidly between 2000 and 2019. The global number of zero-dose children fell by nearly 75% between 1980 and 2019, from 56.8 million (52.6-60. 9) to 14.5 million (13.4-15.9). However, over the past decade, global vaccine coverage broadly plateaued; 94 countries and territories recorded decreasing DTP3 coverage since 2010. Only 11 countries and territories were estimated to have reached the national GVAP target of at least 90% coverage for all assessed vaccines in 2019. Interpretation After achieving large gains in childhood vaccine coverage worldwide, in much of the world this progress was stalled or reversed from 2010 to 2019. These findings underscore the importance of revisiting routine immunisation strategies and programmatic approaches, recentring service delivery around equity and underserved populations. Strengthening vaccine data and monitoring systems is crucial to these pursuits, now and through to 2030, to ensure that all children have access to, and can benefit from, lifesaving vaccines. Copyright (C) 2021 The Author(s). Published by Elsevier Ltd.Peer reviewe

Adolescent transport and unintentional injuries: a systematic analysis using the Global Burden of Disease Study 2019

Background: Globally, transport and unintentional injuries persist as leading preventable causes of mortality and morbidity for adolescents. We sought to report comprehensive trends in injury-related mortality and morbidity for adolescents aged 10–24 years during the past three decades. Methods: Using the Global Burden of Disease, Injuries, and Risk Factors 2019 Study, we analysed mortality and disability-adjusted life-years (DALYs) attributed to transport and unintentional injuries for adolescents in 204 countries. Burden is reported in absolute numbers and age-standardised rates per 100 000 population by sex, age group (10–14, 15–19, and 20–24 years), and sociodemographic index (SDI) with 95% uncertainty intervals (UIs). We report percentage changes in deaths and DALYs between 1990 and 2019. Findings: In 2019, 369 061 deaths (of which 214 337 [58%] were transport related) and 31·1 million DALYs (of which 16·2 million [52%] were transport related) among adolescents aged 10–24 years were caused by transport and unintentional injuries combined. If compared with other causes, transport and unintentional injuries combined accounted for 25% of deaths and 14% of DALYs in 2019, and showed little improvement from 1990 when such injuries accounted for 26% of adolescent deaths and 17% of adolescent DALYs. Throughout adolescence, transport and unintentional injury fatality rates increased by age group. The unintentional injury burden was higher among males than females for all injury types, except for injuries related to fire, heat, and hot substances, or to adverse effects of medical treatment. From 1990 to 2019, global mortality rates declined by 34·4% (from 17·5 to 11·5 per 100 000) for transport injuries, and by 47·7% (from 15·9 to 8·3 per 100 000) for unintentional injuries. However, in low-SDI nations the absolute number of deaths increased (by 80·5% to 42 774 for transport injuries and by 39·4% to 31 961 for unintentional injuries). In the high-SDI quintile in 2010–19, the rate per 100 000 of transport injury DALYs was reduced by 16·7%, from 838 in 2010 to 699 in 2019. This was a substantially slower pace of reduction compared with the 48·5% reduction between 1990 and 2010, from 1626 per 100 000 in 1990 to 838 per 100 000 in 2010. Between 2010 and 2019, the rate of unintentional injury DALYs per 100 000 also remained largely unchanged in high-SDI countries (555 in 2010 vs 554 in 2019; 0·2% reduction). The number and rate of adolescent deaths and DALYs owing to environmental heat and cold exposure increased for the high-SDI quintile during 2010–19. Interpretation: As other causes of mortality are addressed, inadequate progress in reducing transport and unintentional injury mortality as a proportion of adolescent deaths becomes apparent. The relative shift in the burden of injury from high-SDI countries to low and low–middle-SDI countries necessitates focused action, including global donor, government, and industry investment in injury prevention. The persisting burden of DALYs related to transport and unintentional injuries indicates a need to prioritise innovative measures for the primary prevention of adolescent injury. Funding: Bill & Melinda Gates Foundation