Case stacking below the surface: On the possessor case alternation in Udmurt

In this paper we investigate the case split on the possessor in Udmurt. Traditionally, the choice between ablative and genitive possessor case is said to be driven by the grammatical function (GF) of the XP containing the possessor. We argue that the case split is not driven by GFs; rather, it is determined by the case value of the XP that contains the possessor. Importantly, there is no evidence which points to a possessor raising analysis in Udmurt. Instead, we present an analysis according to which the possessor always bears genitive but may be assigned another structural case by an external head. Due to a morphological constraint, stacked case features fuse into a single feature set in the postsyntactic morphological component. If accusative and genitive stack on the possessor, only the default semantic case marker, i.e., the ablative marker, can realize the resulting feature set. In any other context the genitive marker is chosen. We thus claim that there is no abstract ablative on the possessor; instead, the morphological ablative marker realizes a combination of two abstract structural cases

Insulin Signaling Regulates Mitochondrial Function in Pancreatic β-Cells

Insulin/IGF-I signaling regulates the metabolism of most mammalian tissues including pancreatic islets. To dissect the mechanisms linking insulin signaling with mitochondrial function, we first identified a mitochondria-tethering complex in β-cells that included glucokinase (GK), and the pro-apoptotic protein, BADS. Mitochondria isolated from β-cells derived from β-cell specific insulin receptor knockout (βIRKO) mice exhibited reduced BADS, GK and protein kinase A in the complex, and attenuated function. Similar alterations were evident in islets from patients with type 2 diabetes. Decreased mitochondrial GK activity in βIRKOs could be explained, in part, by reduced expression and altered phosphorylation of BADS. The elevated phosphorylation of p70S6K and JNK1 was likely due to compensatory increase in IGF-1 receptor expression. Re-expression of insulin receptors in βIRKO cells partially restored the stoichiometry of the complex and mitochondrial function. These data indicate that insulin signaling regulates mitochondrial function and have implications for β-cell dysfunction in type 2 diabetes

A distinct metabolic signature predicts development of fasting plasma glucose

ABSTRACT: BACKGROUND: High blood glucose and diabetes are amongst the conditions causing the greatest losses in years of healthy life worldwide. Therefore, numerous studies aim to identify reliable risk markers for development of impaired glucose metabolism and type 2 diabetes. However, the molecular basis of impaired glucose metabolism is so far insufficiently understood. The development of so called `omics' approaches in the recent years promises to identify molecular markers and to further understand the molecular basis of impaired glucose metabolism and type 2 diabetes. Although univariate statistical approaches are often applied, we demonstrate here that the application of multivariate statistical approaches is highly recommended to fully capture the complexity of data gained using high-throughput methods. METHODS: We took blood plasma samples from 172 subjects who participated in the prospective Metabolic Syndrome Berlin Potsdam follow-up study (MESY-BEPO Follow-up). We analysed these samples using Gas Chromatography coupled with Mass Spectrometry (GC-MS), and measured 286 metabolites. Furthermore, fasting glucose levels were measured using standard methods at baseline, and after an average of six years. We did correlation analysis and built linear regression models as well as Random Forest regression models to identify metabolites that predict the development of fasting glucose in our cohort. RESULTS: We found a metabolic pattern consisting of nine metabolites that predicted fasting glucose development with an accuracy of 0.47 in tenfold cross-validation using Random Forest regression. We also showed that adding established risk markers did not improve the model accuracy. However, external validation is eventually desirable. Although not all metabolites belonging to the final pattern are identified yet, the pattern directs attention to amino acid metabolism, energy metabolism and redox homeostasis. CONCLUSIONS: We demonstrate that metabolites identified using a high-throughput method (GC-MS) perform well in predicting the development of fasting plasma glucose over several years. Notably, not single, but a complex pattern of metabolites propels the prediction and therefore reflects the complexity of the underlying molecular mechanisms. This result could only be captured by application of multivariate statistical approaches. Therefore, we highly recommend the usage of statistical methods that seize the complexity of the information given by high-throughput methods

Online fit of an analytical response matrix model for orbit correction and optical function measurement

At the Karlsruhe Research Accelerator (KARA), an analytical online model of the orbit response matrix (ORM) has been developed and tested. The model, called the bilinear-exponential model with dispersion (BE+d model), is derived from the Mais-Ripken formalism describing coupled betatron motion. Compared to the standard approach of measuring the ORM, this method continuously adapts to changing beam optics without a dedicated measurement. It is especially useful for storage rings without turn-by-turn capable beam position monitors (BPMs) as the online model also gives access to estimates of the coupled optical functions. In the following, experimental orbit correction results and a comparison of fitted and simulated optical functions are presented

Split-ring resonator experiments and data analysis at FLUTE

FLUTE (Ferninfrarot Linac- Und Test-Experiment) is a compact linac-based test facility for accelerator and diagnostics R&D located at the Karlsruher Institute of Technology (KIT). A new accelerator diagnostics tool, called the split-ring resonator (SRR), was tested at FLUTE, which aims at measuring the longitudinal bunch profile of fs-scale electron bunches. Laser-generated THz radiation is used to excite a high frequency oscillating electromagnetic field in the SRR. Electrons passing through the 20 µm x 20 µm SRR gap are time-dependently deflected in the vertical plane, leading to a vertical streaking of the electron bunch. During the commissioning of the SRR at FLUTE, large series of streaking attempts with varying machine parameters and set-ups were investigated in an automatized way. The recorded beam screen images during this experiment have been analyzed and evaluated. This contribution motivates and presents the automatized experiment and discusses the data analysis

Investigations on NbTi superconducting racetrack coils under pulsed-current excitations

One of the key issues in the technology of superconductors is the protection against quenches. When designing a superconductor as a magnet, a coil or even current leads, the design should be made such that the superconductor withstands all operational conditions as fast discharges, pulsed loads or even rapid transient background fields. Computational modeling of pulsed-current characterization in a self-field NbTi racetrack sample coil has been performed using the finite element modelling software Opera as a step towards understanding the thermal and electromagnetic processes during a quench. The pulse was modelled to be generated by discharging a capacitor into an RLC circuit, which includes the NbTi racetrack coil as the sample under test. The coil was driven to the resistive state and the quench occurred by applying the pulse with a peak value exceeding the critical current of the sample coil. This contribution presents the results obtained from investigating a pulsed NbTi coil in a model based on an electromagnetic analysis. In addition, a comparison to the theoretical expectations derived for the damped oscillations in the pulse-driving circuit is given. Finally, the results from a coupled analysis, where both thermal and electromagnetic properties are being considered, within a quench multi-physics study are presented

Characterization and optimization of laser-generated THz beam for THz based streaking

At the Ferninfrarot Linac- und Test-Experiment (FLUTE) at the Karlsruhe Institute of Technology (KIT) a new and compact method for longitudinal diagnostics of ultrashort electron bunches is being developed. For this technique, which is based on THz streaking, strong electromagnetic pulses with frequencies around 240 GHz are required. Therefore, a setup for laser-generated THz radiation using tilted-pulse-front pumping in lithium niobate was designed, delivering up to 1 µJ of THz pulse energy with a conversion efficiency of up to 0.03 %. In this contribution we study the optimization of the THz beam transport and environment

A low-latency feedback system for the control of horizontal betatron oscillations

Reinforcement learning (RL) algorithms are investigated at KIT as an option to control the beam dynamics at storage rings. These methods require specialized hardware to satisfy throughput and latency constraints dictated by the timescale of the relevant phenomena. The KINGFISHER platform, based on the novel Xilinx Versal Adaptive Compute and Acceleration Platform, is an ideal candidate to deploy RL-on-a-chip thanks to its ability to execute computationally intensive and low latency feedback loops in the order of tens of microseconds. In this publication, we will present the integration of the KINGFISHER system at the Karlsruhe Research Accelerator (KARA), as a proof-of-principle turn-by-turn control feedback loop, to control induced transversal oscillations of an electron beam

Electron beam test facilities for novel applications

Delivering and tailoring high brightness electron beams for a wide range of novel applications is a challenging task in single pass accelerator test facilities. This paper will review beam dynamics challenges at single pass accelerator test facilities in Europe to generate, transport and tailor low- to medium-energy high brightness electron beams for a range of novel applications