Development of PUNDA (Parametric Universal Nonlinear Dynamics Approximator) Models for Self-Validating Knowledge-Guided Modelling of Nonlinear Processes in Particle Accelerators \& Industry

The difficult problems being tackled in the accelerator community are those that are nonlinear, substantially unmodeled, and vary over time. Such problems are ideal candidates for model-based optimization and control if representative models of the problem can be developed that capture the necessary mathematical relations and remain valid throughout the operation region of the system, and through variations in system dynamics. The goal of this proposal is to develop the methodology and the algorithms for building high-fidelity mathematical representations of complex nonlinear systems via constrained training of combined first-principles and neural network models

An island view of endemic rarity—Environmental drivers and consequences for nature conservation

Aim: Rarity—an important measure for conservation biogeography—can vary over many orders of magnitude. However, it is unclear which regional-scale abiotic conditions drive processes affecting rarity of endemic species on islands. To support conservation efforts, we (1) assess the main abiotic drivers of endemic rarity, (2) determine how well existing protected areas (PAs) coincide with hotspots of endemic rarity and (3) introduce and evaluate a new hypervolume-based rarity estimator. Location: La Palma (Canary Islands). Methods: We recorded all present endemic vascular plant species in 1,212 plots covering the entire island. We calculated endemic rarity (corrected range-rarity richness for endemics) using a rarity estimation approach based on kernel density estimations (hypervolume approach). We performed a sensitivity analysis based on multiple linear regressions and relative importance estimations of environmental drivers to estimate the performance of the hypervolume-based rarity estimation compared to standard methods (occurrence frequency, convex hulls, alpha hulls). Results: Climate variables (mean annual temperature, climatic rarity, precipitation variability) best explained archipelago endemic (AE) and single-island endemic (SIE) rarity. Existing PAs covered the majority of AE and SIE rarity, especially national and natural parks as well as the Natura 2000 sites. In our study system, hypervolumes performed better than standard measures of range size. Main conclusion: Both AE and SIE rarity on La Palma show a clear spatial pattern, with hotspots of endemic rarity found at high elevations and in rare climates, presumably owing to geographical and climatic constraints and possibly anthropogenic pressure (e.g., land use, introduced herbivores, fire). Areas of high rarity estimates coincide with the distribution and extent of PAs on La Palma, especially since the recent addition of the Natura 2000 sites. The hypervolume approach is a promising tool to estimate species range sizes, and can be applied on all scales where point/plot data are available.European UnionElite Network of Bavari

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements

Bi-allelic Loss-of-Function CACNA1B Mutations in Progressive Epilepsy-Dyskinesia.

The occurrence of non-epileptic hyperkinetic movements in the context of developmental epileptic encephalopathies is an increasingly recognized phenomenon. Identification of causative mutations provides an important insight into common pathogenic mechanisms that cause both seizures and abnormal motor control. We report bi-allelic loss-of-function CACNA1B variants in six children from three unrelated families whose affected members present with a complex and progressive neurological syndrome. All affected individuals presented with epileptic encephalopathy, severe neurodevelopmental delay (often with regression), and a hyperkinetic movement disorder. Additional neurological features included postnatal microcephaly and hypotonia. Five children died in childhood or adolescence (mean age of death: 9 years), mainly as a result of secondary respiratory complications. CACNA1B encodes the pore-forming subunit of the pre-synaptic neuronal voltage-gated calcium channel Cav2.2/N-type, crucial for SNARE-mediated neurotransmission, particularly in the early postnatal period. Bi-allelic loss-of-function variants in CACNA1B are predicted to cause disruption of Ca2+ influx, leading to impaired synaptic neurotransmission. The resultant effect on neuronal function is likely to be important in the development of involuntary movements and epilepsy. Overall, our findings provide further evidence for the key role of Cav2.2 in normal human neurodevelopment.MAK is funded by an NIHR Research Professorship and receives funding from the Wellcome Trust, Great Ormond Street Children's Hospital Charity, and Rosetrees Trust. E.M. received funding from the Rosetrees Trust (CD-A53) and Great Ormond Street Hospital Children's Charity. K.G. received funding from Temple Street Foundation. A.M. is funded by Great Ormond Street Hospital, the National Institute for Health Research (NIHR), and Biomedical Research Centre. F.L.R. and D.G. are funded by Cambridge Biomedical Research Centre. K.C. and A.S.J. are funded by NIHR Bioresource for Rare Diseases. The DDD Study presents independent research commissioned by the Health Innovation Challenge Fund (grant number HICF-1009-003), a parallel funding partnership between the Wellcome Trust and the Department of Health, and the Wellcome Trust Sanger Institute (grant number WT098051). We acknowledge support from the UK Department of Health via the NIHR comprehensive Biomedical Research Centre award to Guy's and St. Thomas' National Health Service (NHS) Foundation Trust in partnership with King's College London. This research was also supported by the NIHR Great Ormond Street Hospital Biomedical Research Centre. J.H.C. is in receipt of an NIHR Senior Investigator Award. The research team acknowledges the support of the NIHR through the Comprehensive Clinical Research Network. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR, Department of Health, or Wellcome Trust. E.R.M. acknowledges support from NIHR Cambridge Biomedical Research Centre, an NIHR Senior Investigator Award, and the University of Cambridge has received salary support in respect of E.R.M. from the NHS in the East of England through the Clinical Academic Reserve. I.E.S. is supported by the National Health and Medical Research Council of Australia (Program Grant and Practitioner Fellowship)