Catch me if you can: Signal localization with knockoff e-values

We consider problems where many, somewhat redundant, hypotheses are tested and we are interested in reporting the most precise rejections, with false discovery rate (FDR) control. For example, a common goal in genetics is to identify DNA variants that carry distinct information on a trait of interest. However, strong local dependencies between nearby variants make it challenging to distinguish which of the many correlated features most directly influence the phenotype. A common solution is then to identify sets of variants that cover the truly important ones. Depending on the signal strengths, it is possible to resolve the individual variant contributions with more or less precision. Assuring FDR control on the reported findings with these adaptive searches is, however, often impossible. To design a multiple comparison procedure that allows for an adaptive choice of resolution with FDR control, we leverage e-values and linear programming. We adapt this approach to problems where knockoffs and group knockoffs have been successfully applied to test conditional independence hypotheses. We demonstrate its efficacy by analyzing data from the UK Biobank.Comment: 43 pages, 34 figures; text edit

Famotidine use and quantitative symptom tracking for COVID-19 in non-hospitalised patients: a case series.

OBJECTIVE: Treatment options for non-hospitalised patients with coronavirus disease 2019 (COVID-19) to reduce morbidity, mortality and spread of the disease are an urgent global need. The over-the-counter histamine-2 receptor antagonist famotidine is a putative therapy for COVID-19. We quantitively assessed longitudinal changes in patient reported outcome measures in non-hospitalised patients with COVID-19 who self-administered high-dose famotidine orally. DESIGN: Patients were enrolled consecutively after signing written informed consent. Data on demographics, COVID-19 diagnosis, famotidine use, drug-related side effects, temperature measurements, oxygen saturations and symptom scores were obtained using questionnaires and telephone interviews. Based on a National Institute of Health (NIH)-endorsed Protocol to research Patient Experience of COVID-19, we collected longitudinal severity scores of five symptoms (cough, shortness of breath, fatigue, headaches and anosmia) and general unwellness on a four-point ordinal scale modelled on performance status scoring. All data are reported at the patient level. Longitudinal combined normalised symptom scores were statistically compared. RESULTS: Ten consecutive patients with COVID-19 who self-administered high-dose oral famotidine were identified. The most frequently used famotidine regimen was 80 mg three times daily (n=6) for a median of 11 days (range: 5-21 days). Famotidine was well tolerated. All patients reported marked improvements of disease related symptoms after starting famotidine. The combined symptom score improved significantly within 24 hours of starting famotidine and peripheral oxygen saturation (n=2) and device recorded activity (n=1) increased. CONCLUSIONS: The results of this case series suggest that high-dose oral famotidine is well tolerated and associated with improved patient-reported outcomes in non-hospitalised patients with COVID-19

Differential localization of flavonoid glucosides in an aquatic plant implicates different functions under abiotic stress

Abstract Flavonoids may mediate UV protection in plants either by screening of harmful radiation or by minimizing the resulting oxidative stress. To help distinguish between these alternatives, more precise knowledge of flavonoid distribution is needed. We used confocal laser scanning microscopy (cLSM) with the “emission fingerprinting” feature to study the cellular and subcellular distribution of flavonoid glucosides in the giant duckweed ( Spirodela polyrhiza ), and investigated the fitness effects of these compounds under natural UV radiation and copper sulphate addition (oxidative stress) using common garden experiments indoors and outdoors. cLSM “emission fingerprinting” allowed us to individually visualize the major dihydroxylated B‐ring‐substituted flavonoids, luteolin 7‐O‐glucoside and luteolin 8‐C‐glucoside, in cross‐sections of the photosynthetic organs. While luteolin 8‐C‐glucoside accumulated mostly in the vacuoles and chloroplasts of mesophyll cells, luteolin 7‐O‐glucoside was predominantly found in the vacuoles of epidermal cells. In congruence with its cellular distribution, the mesophyll‐associated luteolin 8‐C‐glucoside increased plant fitness under copper sulphate addition but not under natural UV light treatment, whereas the epidermis‐associated luteolin 7‐O‐glucoside tended to increase fitness under both stresses across chemically diverse genotypes. Taken together, we demonstrate that individual flavonoid glucosides have distinct cellular and subcellular locations and promote duckweed fitness under different abiotic stresses

Low genetic variation is associated with low mutation rate in the giant duckweed

Mutation rate and effective population size (Ne) jointly determine intraspecific genetic diversity, but the role of mutation rate is often ignored. We investigate genetic diversity, spontaneous mutation rate and Ne in the giant duckweed (Spirodela polyrhiza). Despite its large census population size, whole-genome sequencing of 68 globally sampled individuals revealed extremely low within-species genetic diversity. Assessed under natural conditions, the genome-wide spontaneous mutation rate is at least seven times lower than estimates made for other multicellular eukaryotes, whereas Ne is large. These results demonstrate that low genetic diversity can be associated with large-Ne species, where selection can reduce mutation rates to very low levels, and accurate estimates of mutation rate can help to explain seemingly counter-intuitive patterns of genome-wide variation

PolyJet-Printed Bellows Actuators: Design, Structural Optimization, and Experimental Investigation

Pneumatic bellows actuators are exceptionally suitable for Additive Manufacturing (AM) as the required geometrical complexity can easily be obtained and their functionality is not affected by rough surfaces and small dimensional accuracy. This paper is an extended version of a previously published contribution to the RoboSoft2018 conference in Livorno, Italy. The original paper (Dämmer et al., 2018) contains a simulation-driven design approach as well as experimental investigations of the structural and fatigue behavior of pneumatic multi-material PolyJet™ bellows actuators. This extended version is enhanced with investigations on the relaxation behavior of PolyJet bellows actuators. The presented results are useful for researchers and engineers considering the application of PolyJet bellows actuators for pneumatic robots

Towards the virtualization of a sound source localization acuity test to aid the diagnosis of spatial processing disorder in school-aged children: An experimental approach

Spatial hearing is an essential auditory function. It allows us to localize, segregate, and group sound sources in space. Accurate sound source localization is a fundamental ability for understanding and following speech in everyday situations, as it contributes to our capacity to discern between target signal streams and other simultaneous sound sources that can be regarded as noise (cocktail party processing).BMBF, 13FH666IA6, IngenieurNachwuchs 2016: Binaurales Hören in der realen und virtuellen Welt zur Verbesserung der Hör-Erfahrung von Schulkindern (VIWER-S