Database-Inspired Optimizations for Statistical Analysis

Computing complex statistics on large amounts of data is no longer a corner case, but a daily challenge. However, current tools such as GNU R were not built to efficiently handle large data sets. We propose to vastly improve the execution of R scripts by interpreting them as a declaration of intent rather than an imperative order set in stone. This allows us to apply optimization techniques from the columnar data management research field. We have implemented several of these optimizers in Renjin, an open-source execution environment for R scripts targeted at the Java virtual machine. The demonstration of our approach using a series of micro-benchmarks and experiments on complex survey analysis show orders-of-magnitude improvements in analysis cost

Battery-Electric Powertrain System Design for the HorizonUAM Multirotor Air Taxi Concept

The work presented herein has been conducted within the DLR internal research project HorizonUAM, which encompasses research within numerous areas related to urban air mobility. One of the project goals was to develop a safe and certifiable onboard system concept. This paper aims to present the conceptual propulsion system architecture design for an all-electric battery-powered multirotor electric Vertical Takeoff and Landing (eVTOL) vehicle. Therefore, a conceptual design method was developed that provides a structured approach for designing the safe multirotor propulsion architecture. Based on the concept of operation the powertrain system was initially predefined, iteratively refined based on the safety assessment and validated through component sizing and simulations. The analysis was conducted within three system groups that were developed in parallel: the drivetrain, the energy supply and the thermal management system. The design process indicated that a pure quadcopter propulsion system can merely be designed reasonably for meeting the European Union Aviation Safety Agency (EASA) reliability specifications. By adding two push propellers and implementing numerous safety as well as passivation measures the reliability specifications defined by EASA could finally be fulfilled. The subsequent system simulations also verified that the system architecture is capable of meeting the requirements of the vehicle concept of operations. However, further work is required to extend the safety analysis to additional system components as the thermal management system or the battery management system and to reduce propulsion system weight.Comment: 38 pages, 27 figures, CEAS Aeronautical Journal Special Issue "HorizonUAM - Opportunities and Challenges of Urban Air Mobility

A Concept for a Mars Boundary Layer Sounding Balloon: Science Case, Technical Concept and Deployment Risk Analysis

The Mars Exploration Program Analysis Group has identified measurements of the state and the variability of the Martian atmosphere as high priority investigations for the upcoming years. Balloon-borne instruments could bridge the gap in both temporal and spatial resolution in mesoscale distances between local, stationary landers and global orbiter observations. The idea to use a balloon system for such a purpose is not new in essence and has been proposed already in past decades. While those concepts considered an aerial deployment during entry and descent, the concept outlined in this study revisits a launch off the payload deck of a lander from the Martian surface. This deployment option profits today mainly from the technological advance in micro-electronics and sensor miniaturization, which enables the design of a balloon-probe significantly smaller than earlier proposed systems. This paper presents the feasibility assessment for this instrument and gives further details on the scientific and operational concept, a strawman sensor suite, its system components and the associated size and budget estimates. It is complemented by the analysis scheme proposed to assess, manage and mitigate the deployment risk involved in automatically launching such a balloon-system off a planetary surface

SKP2 attenuates autophagy through Beclin1-ubiquitination and its inhibition reduces MERS-Coronavirus infection

Autophagy is an essential cellular process affecting virus infections and other diseases and Beclin1 (BECN1) is one of its key regulators. Here, we identified S-phase kinase-associated protein 2 (SKP2) as E3 ligase that executes lysine-48-linked poly-ubiquitination of BECN1, thus promoting its proteasomal degradation. SKP2 activity is regulated by phosphorylation in a hetero-complex involving FKBP51, PHLPP, AKT1, and BECN1. Genetic or pharmacological inhibition of SKP2 decreases BECN1 ubiquitination, decreases BECN1 degradation and enhances autophagic flux. Middle East respiratory syndrome coronavirus (MERS-CoV) multiplication results in reduced BECN1 levels and blocks the fusion of autophagosomes and lysosomes. Inhibitors of SKP2 not only enhance autophagy but also reduce the replication of MERS-CoV up to 28,000-fold. The SKP2-BECN1 link constitutes a promising target for host-directed antiviral drugs and possibly other autophagy-sensitive conditions

Short term policies to keep the door open for Paris climate goals

Climate policy needs to account for political and social acceptance. Current national climate policy plans proposed under the Paris Agreement lead to higher emissions until 2030 than cost-effective pathways towards the Agreements’ long-term temperature goals would imply. Therefore, the current plans would require highly disruptive changes, prohibitive transition speeds, and large long-term deployment of risky mitigation measures for achieving the agreement’s temperature goals after 2030. Since the prospects of introducing the cost-effective policy instrument, a global comprehensive carbon price in the near-term, are negligible, we study how a strengthening of existing plans by a global roll-out of regional policies can ease the implementation challenge of reaching the Paris temperature goals. The regional policies comprise a bundle of regulatory policies in energy supply, transport, buildings, industry, and land use and moderate, regionally differentiated carbon pricing. We find that a global roll-out of these policies could reduce global CO2 emissions by an additional 10 GtCO2eq in 2030 compared to current plans. It would lead to emissions pathways close to the levels of cost-effective likely below 2 °C scenarios until 2030, thereby reducing implementation challenges post 2030. Even though a gradual phase-in of a portfolio of regulatory policies might be less disruptive than immediate cost-effective carbon pricing, it would perform worse in other dimensions. In particular, it leads to higher economic impacts that could become major obstacles in the long-term. Hence, such policy packages should not be viewed as alternatives to carbon pricing, but rather as complements that provide entry points to achieve the Paris climate goals

An Analysis of Two Genome-wide Association Meta-analyses Identifies a New Locus for Broad Depression Phenotype

AbstractBackgroundThe genetics of depression has been explored in genome-wide association studies that focused on either major depressive disorder or depressive symptoms with mostly negative findings. A broad depression phenotype including both phenotypes has not been tested previously using a genome-wide association approach. We aimed to identify genetic polymorphisms significantly associated with a broad phenotype from depressive symptoms to major depressive disorder.MethodsWe analyzed two prior studies of 70,017 participants of European ancestry from general and clinical populations in the discovery stage. We performed a replication meta-analysis of 28,328 participants. Single nucleotide polymorphism (SNP)-based heritability and genetic correlations were calculated using linkage disequilibrium score regression. Discovery and replication analyses were performed using a p-value-based meta-analysis. Lifetime major depressive disorder and depressive symptom scores were used as the outcome measures.ResultsThe SNP-based heritability of major depressive disorder was 0.21 (SE = 0.02), the SNP-based heritability of depressive symptoms was 0.04 (SE = 0.01), and their genetic correlation was 1.001 (SE = 0.2). We found one genome-wide significant locus related to the broad depression phenotype (rs9825823, chromosome 3: 61,082,153, p = 8.2 × 10–9) located in an intron of the FHIT gene. We replicated this SNP in independent samples (p = .02) and the overall meta-analysis of the discovery and replication cohorts (1.0 × 10–9).ConclusionsThis large study identified a new locus for depression. Our results support a continuum between depressive symptoms and major depressive disorder. A phenotypically more inclusive approach may help to achieve the large sample sizes needed to detect susceptibility loci for depression

Genome-wide interaction study of a proxy for stress-sensitivity and its prediction of major depressive disorder

Individual response to stress is correlated with neuroticism and is an important predictor of both neuroticism and the onset of major depressive disorder (MDD). Identification of the genetics underpinning individual differences in response to negative events (stress-sensitivity) may improve our understanding of the molecular pathways involved, and its association with stress-related illnesses. We sought to generate a proxy for stress-sensitivity through modelling the interaction between SNP allele and MDD status on neuroticism score in order to identify genetic variants that contribute to the higher neuroticism seen in individuals with a lifetime diagnosis of depression compared to unaffected individuals. Meta-analysis of genome-wide interaction studies (GWIS) in UK Biobank (N = 23,092) and Generation Scotland: Scottish Family Health Study (N = 7,155) identified no genome-wide significance SNP interactions. However, gene-based tests identified a genome-wide significant gene, ZNF366, a negative regulator of glucocorticoid receptor function implicated in alcohol dependence (p = 1.48x10-7; Bonferroni-corrected significance threshold p < 2.79x10-6). Using summary statistics from the stress-sensitivity term of the GWIS, SNP heritability for stress-sensitivity was estimated at 5.0%. In models fitting polygenic risk scores of both MDD and neuroticism derived from independent GWAS, we show that polygenic risk scores derived from the UK Biobank stress-sensitivity GWIS significantly improved the prediction of MDD in Generation Scotland. This study may improve interpretation of larger genome-wide association studies of MDD and other stress-related illnesses, and the understanding of the etiological mechanisms underpinning stress-sensitivity

Polygenic prediction of educational attainment within and between families from genome-wide association analyses in 3 million individuals

We conduct a genome-wide association study (GWAS) of educational attainment (EA) in a sample of ~3 million individuals and identify 3,952 approximately uncorrelated genome-wide-significant single-nucleotide polymorphisms (SNPs). A genome-wide polygenic predictor, or polygenic index (PGI), explains 12-16% of EA variance and contributes to risk prediction for ten diseases. Direct effects (i.e., controlling for parental PGIs) explain roughly half the PGI's magnitude of association with EA and other phenotypes. The correlation between mate-pair PGIs is far too large to be consistent with phenotypic assortment alone, implying additional assortment on PGI-associated factors. In an additional GWAS of dominance deviations from the additive model, we identify no genome-wide-significant SNPs, and a separate X-chromosome additive GWAS identifies 57

Combined Forward-Backward Asymmetry Measurements in Top-Antitop Quark Production at the Tevatron

The CDF and D0 experiments at the Fermilab Tevatron have measured the asymmetry between yields of forward- and backward-produced top and antitop quarks based on their rapidity difference and the asymmetry between their decay leptons. These measurements use the full data sets collected in proton-antiproton collisions at a center-of-mass energy of $\sqrt s =1.96$ TeV. We report the results of combinations of the inclusive asymmetries and their differential dependencies on relevant kinematic quantities. The combined inclusive asymmetry is $A_{\mathrm{FB}}^{t\bar{t}} = 0.128 \pm 0.025$. The combined inclusive and differential asymmetries are consistent with recent standard model predictions