RNA-aptamers-in-droplets (RAPID) high-throughput screening for secretory phenotypes.

Synthetic biology and metabolic engineering seek to re-engineer microbes into living foundries for the production of high value chemicals. Through a design-build-test cycle paradigm, massive libraries of genetically engineered microbes can be constructed and tested for metabolite overproduction and secretion. However, library generation capacity outpaces the rate of high-throughput testing and screening. Well plate assays are flexible but with limited throughput, whereas droplet microfluidic techniques are ultrahigh-throughput but require a custom assay for each target. Here we present RNA-aptamers-in-droplets (RAPID), a method that greatly expands the generality of ultrahigh-throughput microfluidic screening. Using aptamers, we transduce extracellular product titer into fluorescence, allowing ultrahigh-throughput screening of millions of variants. We demonstrate the RAPID approach by enhancing production of tyrosine and secretion of a recombinant protein in Saccharomyces cerevisiae by up to 28- and 3-fold, respectively. Aptamers-in-droplets affords a general approach for evolving microbes to synthesize and secrete value-added chemicals.Screening libraries of genetically engineered microbes for secreted products is limited by the available assay throughput. Here the authors combine aptamer-based fluorescent detection with droplet microfluidics to achieve high throughput screening of yeast strains engineered for enhanced tyrosine or streptavidin production

Master Recital

Program listing performers and works performe

On Imperfect Recall in Multi-Agent Influence Diagrams

Multi-agent influence diagrams (MAIDs) are a popular game-theoretic model based on Bayesian networks. In some settings, MAIDs offer significant advantages over extensive-form game representations. Previous work on MAIDs has assumed that agents employ behavioural policies, which set independent conditional probability distributions over actions for each of their decisions. In settings with imperfect recall, however, a Nash equilibrium in behavioural policies may not exist. We overcome this by showing how to solve MAIDs with forgetful and absent-minded agents using mixed policies and two types of correlated equilibrium. We also analyse the computational complexity of key decision problems in MAIDs, and explore tractable cases. Finally, we describe applications of MAIDs to Markov games and team situations, where imperfect recall is often unavoidable.Comment: In Proceedings TARK 2023, arXiv:2307.0400

Master\u27s Recital

Program listing performers and works performe

Master Recital

Program listing performers and works performe

Global, regional, and national incidence, prevalence, andyears lived with disability for 354 diseases and injuries for195 countries and territories, 1990–2017: a systematicanalysis for the Global Burden of Disease Study 2017

The Global Burden of Diseases, Injuries, and Risk Factors Study 2017 (GBD 2017) includes a comprehensive assessment of incidence, prevalence, and years lived with disability (YLDs) for 354 causes in 195 countries and territories from 1990 to 2017. Previous GBD studies have shown how the decline of mortality rates from 1990 to 2016 has led to an increase in life expectancy, an ageing global population, and an expansion of the non-fatal burden of disease and injury. These studies have also shown how a substantial portion of the world’s population experiences non-fatal health loss with considerable heterogeneity among different causes, locations, ages, and sexes. Ongoing objectives of the GBD study include increasing the level of estimation detail, improving analytical strategies, and increasing the amount of high-quality data.Research reported in this publication was supported by the Bill & Melinda Gates Foundation, the University of Melbourne, Public Health England, the Norwegian Institute of Public Health, St Jude Children’s Research Hospital, the National Institute on Ageing of the National Institutes of Health (award P30AG047845), and the National Institute of Mental Health of the National Institutes of Health (award R01MH110163)

Hubble Space Telescope Near-Ultraviolet Spectroscopy of Bright CEMP-s Stars

We present an elemental-abundance analysis, in the near-ultraviolet (NUV) spectral range, for the bright carbon-enhanced metal-poor (CEMP) stars HD196944 (V = 8.40, [Fe/H] = -2.41) and HD201626 (V = 8.16, [Fe/H] = -1.51), based on data acquired with the Space Telescope Imaging Spectrograph (STIS) on the Hubble Space Telescope. Both of these stars belong to the sub-class CEMP-s, and exhibit clear over-abundances of heavy elements associated with production by the slow neutron-capture process. HD196944 has been well-studied in the optical region, but we are able to add abundance results for six species (Ge, Nb, Mo, Lu, Pt, and Au) that are only accessible in the NUV. In addition, we provide the first determination of its orbital period, P=1325 days. HD201626 has only a limited number of abundance results based on previous optical work -- here we add five new species from the NUV, including Pb. We compare these results with models of binary-system evolution and s-process element production in stars on the asymptotic giant branch, aiming to explain their origin and evolution. Our best-fitting models for HD 196944 (M1,i = 0.9Mo, M2,i = 0.86Mo, for [Fe/H]=-2.2), and HD 201626 (M1,i = 0.9Mo , M2,i = 0.76Mo , for [Fe/H]=-2.2; M1,i = 1.6Mo , M2,i = 0.59Mo, for [Fe/H]=-1.5) are consistent with the current accepted scenario for the formation of CEMP-s stars.Comment: 25 pages, 13 figures; accepted for publication in Ap

Global, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990-2017 : a systematic analysis for the global burden of disease study 2017

Background: The Global Burden of Diseases, Injuries, and Risk Factors Study 2017 (GBD 2017) includes a comprehensive assessment of incidence, prevalence, and years lived with disability (YLDs) for 354 causes in 195 countries and territories from 1990 to 2017. Previous GBD studies have shown how the decline of mortality rates from 1990 to 2016 has led to an increase in life expectancy, an ageing global population, and an expansion of the non-fatal burden of disease and injury. These studies have also shown how a substantial portion of the world's population experiences non-fatal health loss with considerable heterogeneity among different causes, locations, ages, and sexes. Ongoing objectives of the GBD study include increasing the level of estimation detail, improving analytical strategies, and increasing the amount of high-quality data. Methods: We estimated incidence and prevalence for 354 diseases and injuries and 3484 sequelae. We used an updated and extensive body of literature studies, survey data, surveillance data, inpatient admission records, outpatient visit records, and health insurance claims, and additionally used results from cause of death models to inform estimates using a total of 68 781 data sources. Newly available clinical data from India, Iran, Japan, Jordan, Nepal, China, Brazil, Norway, and Italy were incorporated, as well as updated claims data from the USA and new claims data from Taiwan (province of China) and Singapore. We used DisMod-MR 2.1, a Bayesian meta-regression tool, as the main method of estimation, ensuring consistency between rates of incidence, prevalence, remission, and cause of death for each condition. YLDs were estimated as the product of a prevalence estimate and a disability weight for health states of each mutually exclusive sequela, adjusted for comorbidity. We updated the Socio-demographic Index (SDI), a summary development indicator of income per capita, years of schooling, and total fertility rate. Additionally, we calculated differences between male and female YLDs to identify divergent trends across sexes. GBD 2017 complies with the Guidelines for Accurate and Transparent Health Estimates Reporting. Findings: Globally, for females, the causes with the greatest age-standardised prevalence were oral disorders, headache disorders, and haemoglobinopathies and haemolytic anaemias in both 1990 and 2017. For males, the causes with the greatest age-standardised prevalence were oral disorders, headache disorders, and tuberculosis including latent tuberculosis infection in both 1990 and 2017. In terms of YLDs, low back pain, headache disorders, and dietary iron deficiency were the leading Level 3 causes of YLD counts in 1990, whereas low back pain, headache disorders, and depressive disorders were the leading causes in 2017 for both sexes combined. All-cause age-standardised YLD rates decreased by 3·9% (95% uncertainty interval [UI] 3·1-4·6) from 1990 to 2017; however, the all-age YLD rate increased by 7·2% (6·0-8·4) while the total sum of global YLDs increased from 562 million (421-723) to 853 million (642-1100). The increases for males and females were similar, with increases in all-age YLD rates of 7·9% (6·6-9·2) for males and 6·5% (5·4-7·7) for females. We found significant differences between males and females in terms of age-standardised prevalence estimates for multiple causes. The causes with the greatest relative differences between sexes in 2017 included substance use disorders (3018 cases [95% UI 2782-3252] per 100 000 in males vs 1400 [1279-1524] per 100 000 in females), transport injuries (3322 [3082-3583] vs 2336 [2154-2535]), and self-harm and interpersonal violence (3265 [2943-3630] vs 5643 [5057-6302]). Interpretation: Global all-cause age-standardised YLD rates have improved only slightly over a period spanning nearly three decades. However, the magnitude of the non-fatal disease burden has expanded globally, with increasing numbers of people who have a wide spectrum of conditions. A subset of conditions has remained globally pervasive since 1990, whereas other conditions have displayed more dynamic trends, with different ages, sexes, and geographies across the globe experiencing varying burdens and trends of health loss. This study emphasises how global improvements in premature mortality for select conditions have led to older populations with complex and potentially expensive diseases, yet also highlights global achievements in certain domains of disease and injury