Nonparametric inference on median residual life function

Summary. A simple approach to the estimation of the median residual lifetime is proposed for a single group by inverting a function of the Kaplan-Meier estimators. A test statistic is proposed to compare two median residual lifetimes at any fixed time point. The test statistic does not involve estimation of the underlying probability density function of failure times under censoring. Extensive simulation studies are performed to validate the proposed test statistic in terms of type I error probabilities and powers at various time points. One of the oldest data sets from the National Surgical Adjuvant Breast and Bowel Project (NSABP), which has more than a quarter century of follow-up, is used to illustrate the method. The analysis results indicate that, without systematic post-operative therapy, a significant difference in median residual lifetimes between node-negative and node-positive breast cancer patients persists for about 10 years after surgery. The new estimates of the median residual lifetime could serve as a baseline for physicians to explain any incremental effects of post-operative treatments in terms of delaying breast cancer recurrence or prolonging remaining lifetimes of breast cancer patients

Nonparametric inference on median residual life function

Summary. A simple approach to the estimation of the median residual lifetime is proposed for a single group by inverting a function of the Kaplan-Meier estimators. A test statistic is proposed to compare two median residual lifetimes at any fixed time point. The test statistic does not involve estimation of the underlying probability density function of failure times under censoring. Extensive simulation studies are performed to validate the proposed test statistic in terms of type I error probabilities and powers at various time points. One of the oldest data sets from the National Surgical Adjuvant Breast and Bowel Project (NSABP), which has more than a quarter century of follow-up, is used to illustrate the method. The analysis results indicate that, without systematic post-operative therapy, a significant difference in median residual lifetimes between node-negative and node-positive breast cancer patients persists for about 10 years after surgery. The new estimates of the median residual lifetime could serve as a baseline for physicians to explain any incremental effects of post-operative treatments in terms of delaying breast cancer recurrence or prolonging remaining lifetimes of breast cancer patients

Drop impact upon micro- and nanostructured superhydrophobic surfaces

We experimentally investigate drop impact dynamics onto different superhydrophobic surfaces, consisting of regular polymeric micropatterns and rough carbon nanofibers, with similar static contact angles. The main control parameters are the Weber number \We and the roughness of the surface. At small \We, i.e. small impact velocity, the impact evolutions are similar for both types of substrates, exhibiting Fakir state, complete bouncing, partial rebouncing, trapping of an air bubble, jetting, and sticky vibrating water balls. At large \We, splashing impacts emerge forming several satellite droplets, which are more pronounced for the multiscale rough carbon nanofiber jungles. The results imply that the multiscale surface roughness at nanoscale plays a minor role in the impact events for small \We \apprle 120 but an important one for large \We \apprge 120. Finally, we find the effect of ambient air pressure to be negligible in the explored parameter regime \We \apprle 150Comment: 8 pages, 7 figure

Search for Neutrinos from the Tidal Disruption Events AT2019dsg and AT2019fdr with the ANTARES Telescope

On 2019 October 1, the IceCube Collaboration detected a muon track neutrino with a high probability of being of astrophysical origin, IC191001A. After a few hours, the tidal disruption event (TDE) AT2019dsg, observed by the Zwicky Transient Facility (ZTF), was indicated as the most likely counterpart of the IceCube track. More recently, the follow-up campaign of the IceCube alerts by ZTF suggested a second TDE, AT2019fdr, as a promising counterpart of another IceCube muon track candidate, IC200530A, detected on 2020 May 30. Here, these intriguing associations are followed-up by searching for neutrinos in the ANTARES detector from the directions of AT2019dsg and AT2019fdr using a time-integrated approach. As no significant evidence for space clustering is found in the ANTARES data, upper limits on the one-flavor neutrino flux and fluence are set

Sensitivity to light sterile neutrino mixing parameters with KM3NeT/ORCA

KM3NeT/ORCA is a next-generation neutrino telescope optimised for atmospheric neutrino oscillations studies. In this paper, the sensitivity of ORCA to the presence of a light sterile neutrino in a 3+1 model is presented. After three years of data taking, ORCA will be able to probe the active-sterile mixing angles θ14, θ24, θ34 and the effective angle θμe, over a broad range of mass squared difference Δm241 ∼ [10−5, 10] eV2, allowing to test the eV-mass sterile neutrino hypothesis as the origin of short baseline anomalies, as well as probing the hypothesis of a very light sterile neutrino, not yet constrained by cosmology. ORCA will be able to explore a relevant fraction of the parameter space not yet reached by present measurements

Inducible Deletion of Protein Kinase Map4k4 in Obese Mice Improves Insulin Sensitivity in Liver and Adipose Tissues

Studies in vitro suggest that mitogen-activated protein kinase kinase kinase kinase 4 (Map4k4) attenuates insulin signaling, but confirmation in vivo is lacking since Map4k4 knockout is lethal during embryogenesis. We thus generated mice with floxed Map4k4 alleles and a tamoxifen-inducible Cre/ERT2 recombinase under the control of the ubiquitin C promoter to induce whole-body Map4k4 deletion after these animals reached maturity. Tamoxifen administration to these mice induced Map4k4 deletion in all tissues examined, causing decreased fasting blood glucose concentrations and enhanced insulin signaling to AKT in adipose tissue and liver but not in skeletal muscle. Surprisingly, however, mice generated with a conditional Map4k4 deletion in adiponectin-positive adipocytes or in albumin-positive hepatocytes displayed no detectable metabolic phenotypes. Instead, mice with Map4k4 deleted in Myf5-positive tissues, including all skeletal muscles tested, were protected from obesity-induced glucose intolerance and insulin resistance. Remarkably, these mice also showed increased insulin sensitivity in adipose tissue but not skeletal muscle, similar to the metabolic phenotypes observed in inducible whole-body knockout mice. Taken together, these results indicate that (i) Map4k4 controls a pathway in Myf5-positive cells that suppresses whole-body insulin sensitivity and (ii) Map4k4 is a potential therapeutic target for improving glucose tolerance and insulin sensitivity in type 2 diabetes

The potato R locus codes for dihydroflavonol 4-reductase

The potato R locus is required for the production of red pelargonidin-based anthocyanin pigments in potato (Solanum tuberosum L.). Red color also requires tissue-specific regulatory genes, such as D (for expression in tuber skin) and F (expression in flowers). A related locus, P, is required for production of blue/purple anthocyanins; P is epistatic to R. We have previously reported that the dihydroflavonol 4-reductase gene (dfr) co-segregates with R. To test directly whether R corresponds to dfr, we placed the allele of dfr associated with red color under the control of the CaMV 35S promoter and introduced it into the potato cultivar Prince Hairy (genotype dddd rrrr P-), which has white tubers and pale blue flowers. Transgenic Prince Hairy tubers remained white, but flower color changed to purple. Three independent transgenic lines, as well as a vector-transformed line, were then crossed with the red-skinned variety Chieftain (genotype D-R-pppp), to establish populations that segregated for D, R, P, and the dfr transgene or empty vector. Markers were used to genotype progeny at D and R. Progeny carrying the empty vector in the genetic background D-rrrr produced white or purple tubers, while progeny with the same genotype and the dfr transgene produced red or purple tubers. HPLC and LC–MS/MS analyses of anthocyanins present in Chieftain and in a red-skinned progeny clone with the dfr transgene in a D-rrrr background revealed no qualitative differences. Thus, dfr can fully complement R, both in terms of tuber color and anthocyanin composition