Climate model bias correction and the role of timescales

It is well known that output from climate models cannot be used to force hydrological simulations without some form of preprocessing to remove the existing biases. In principle, statistical bias correction methodologies act on model output so the statistical properties of the corrected data match those of the observations. However the improvements to the statistical properties of the data are limited to the specific time scale of the fluctuations that are considered. For example, a statistical bias correction methodology for mean daily values might be detrimental to monthly statistics. Also, in applying bias corrections derived from present day to scenario simulations, an assumption is made of persistence of the bias over the largest timescales. We examine the effects of mixing fluctuations on different time scales and suggest an improved statistical methodology, referred to here as a cascade bias correction method, that eliminates, or greatly reduces, the negative effects

Isn't a number and a URL enough? Why PIDs matter and technical solutions alone are not sufficient

In the presentation, we introduce the two projects PID4NFDI and PID Network Germany that deal with PIDs at the national level, present some initial findings and highlight their benefit for NFDI. PIDs are used and needed along the entire lifecycle of research data: from enabling to connecting. However, a particular focus for the presentation will be laid on harmonising and connecting

TDP-43 and FUS mislocalization in VCP mutant motor neurons is reversed by pharmacological inhibition of the VCP D2 ATPase domain

RNA binding proteins have been shown to play a key role in the pathogenesis of amyotrophic lateral sclerosis (ALS). Mutations in valosin-containing protein (VCP/p97) cause ALS and exhibit the hallmark nuclear-to-cytoplasmic mislocalization of RNA binding proteins (RBPs). However, the mechanism by which mutations in VCP lead to this mislocalization of RBPs remains incompletely resolved. To address this, we used human-induced pluripotent stem cell-derived motor neurons carrying VCP mutations. We first demonstrate reduced nuclear-to-cytoplasmic ratios of transactive response DNA-binding protein 43 (TDP-43), fused in sarcoma/translocated in liposarcoma (FUS) and splicing factor proline and glutamine rich (SFPQ) in VCP mutant motor neurons. Upon closer analysis, we also find these RBPs are mislocalized to motor neuron neurites themselves. To address the hypothesis that altered function of the D2 ATPase domain of VCP causes RBP mislocalization, we used pharmacological inhibition of this domain in control motor neurons and found this does not recapitulate RBP mislocalization phenotypes. However, D2 domain inhibition in VCP mutant motor neurons was able to robustly reverse mislocalization of both TDP-43 and FUS, in addition to partially relocalizing SFPQ from the neurites. Together these results argue for a gain-of-function of D2 ATPase in VCP mutant human motor neurons driving the mislocalization of TDP-43 and FUS. Our data raise the intriguing possibility of harnessing VCP D2 ATPase inhibitors in the treatment of VCP-related ALS

Web Service Discovery – Reality Check 2.0

In practice the ability to find the right Web service decides between a functionality being implemented anew and at least the possibility of executing it via a service. This report evaluates existing public portals for Web service discovery with respect to their characteristics and their acceptance by developers. For this, we distinguish different possible settings and use cases and evaluate how these are supported in practice. Only few of the publicly available Web service registries are growing in size and importance, with the use case best supported being the pre-programming phase of evaluation of the service landscape. <br

Detection of a somatic GREB1-NCOA1 gene fusion in a uterine tumor resembling ovarian sex cord tumor (UTROSCT)

Uterine tumor resembling ovarian sex cord tumor (UTROSCT) is a rare uterine neoplasm of uncertain malignant potential. We present the case of a 69-year-old woman who underwent hysterectomy for postmenopausal bleeding and was found to have a myometrial UTROSCT. RNA-sequencing identified a somati