Analysis of electromagnetic interference from power system processing and transmission components for Space Station Freedom

The goal of this research project was to analyze the potential effects of electromagnetic interference (EMI) originating from power system processing and transmission components for Space Station Freedom. The approach consists of four steps: (1) developing analytical tools (models and computer programs); (2) conducting parameterization (what if?) studies; (3) predicting the global space station EMI environment; and (4) providing a basis for modification of EMI standards

Upgrading the beam telescopes at the DESY II Test Beam Facility

The DESY II Test Beam Facility is a key infrastructure for modern high energy physics detector development, providing particles with a small momentum spread in a range from 1 to 6 GeV to user groups e.g. from the LHC experiments and Belle II as well as generic detector R&D. Beam telescopes are provided in all three test beam areas as precise tracking reference without time stamping, with triggered readout and a readout time of >115 $\mu$s . If the highest available rates are used, multiple particles are traversing the telescopes within one readout frame, thus creating ambiguities that cannot be resolved without additional timing layers. Several upgrades are currently investigated and tested: Firstly, a fast monolithic pixel sensor, the TelePix, to provide precise track timing and triggering on a region of interest is proposed to overcome this limitation. The TelePix is a 180 nm HV-CMOS sensor that has been developed jointly by DESY, KIT and the University of Heidelberg and designed at KIT. In this publication, the performance evaluation is presented: The difference between two amplifier designs is evaluated. A high hit detection efficiency of above 99.9 % combined with a time resolution of below 4 ns at negligible pixel noise rates is determined. Finally, the digital hit output to provide region of interest triggering is evaluated and shows a short absolute delay with respect to a traditional trigger scintillator as well as an excellent time resolution. Secondly, a fast LGAD plane has been proposed to provide a time resolution of a few 10 ps, which is foreseen to drastically improve the timing performance of the telescope. Time resolutions of below 70 ps have been determined in collaboration with the University of California, Santa Barbara

MuPix and ATLASPix -- Architectures and Results

High Voltage Monolithic Active Pixel Sensors (HV-MAPS) are based on a commercial High Voltage CMOS process and collect charge by drift inside a reversely biased diode. HV-MAPS represent a promising technology for future pixel tracking detectors. Two recent developments are presented. The MuPix has a continuous readout and is being developed for the Mu3e experiment whereas the ATLASPix is being developed for LHC applications with a triggered readout. Both variants have a fully monolithic design including state machines, clock circuitries and serial drivers. Several prototypes and design variants were characterised in the lab and in testbeam campaigns to measure efficiencies, noise, time resolution and radiation tolerance. Results from recent MuPix and ATLASPix prototypes are presented and prospects for future improvements are discussed.Comment: 10 pages, proceedings, The 28th International Workshop on Vertex Detectors (VERTEX 2019), 13 - 18 Oct 2019, Lopud Island, Croati

Models of <i>KPTN</i>-related disorder implicate mTOR signalling in cognitive and overgrowth phenotypes

KPTN-related disorder is an autosomal recessive disorder associated with germline variants in KPTN (previously known as kaptin), a component of the mTOR regulatory complex KICSTOR. To gain further insights into the pathogenesis of KPTN-related disorder, we analysed mouse knockout and human stem cell KPTN loss-of-function models. Kptn -/- mice display many of the key KPTN-related disorder phenotypes, including brain overgrowth, behavioural abnormalities, and cognitive deficits. By assessment of affected individuals, we have identified widespread cognitive deficits (n = 6) and postnatal onset of brain overgrowth (n = 19). By analysing head size data from their parents (n = 24), we have identified a previously unrecognized KPTN dosage-sensitivity, resulting in increased head circumference in heterozygous carriers of pathogenic KPTN variants. Molecular and structural analysis of Kptn-/- mice revealed pathological changes, including differences in brain size, shape and cell numbers primarily due to abnormal postnatal brain development. Both the mouse and differentiated induced pluripotent stem cell models of the disorder display transcriptional and biochemical evidence for altered mTOR pathway signalling, supporting the role of KPTN in regulating mTORC1. By treatment in our KPTN mouse model, we found that the increased mTOR signalling downstream of KPTN is rapamycin sensitive, highlighting possible therapeutic avenues with currently available mTOR inhibitors. These findings place KPTN-related disorder in the broader group of mTORC1-related disorders affecting brain structure, cognitive function and network integrity.</p

Technical design of the phase I Mu3e experiment

The Mu3e experiment aims to find or exclude the lepton flavour violating decay $\mu \rightarrow eee$ at branching fractions above $10^{-16}$. A first phase of the experiment using an existing beamline at the Paul Scherrer Institute (PSI) is designed to reach a single event sensitivity of $2\cdot 10^{-15}$. We present an overview of all aspects of the technical design and expected performance of the phase~I Mu3e detector. The high rate of up to $10^{8}$ muon decays per second and the low momenta of the decay electrons and positrons pose a unique set of challenges, which we tackle using an ultra thin tracking detector based on high-voltage monolithic active pixel sensors combined with scintillating fibres and tiles for precise timing measurements.Comment: 114 pages, 185 figures. Submitted to Nuclear Instruments and Methods A. Edited by Frank Meier Aeschbacher This version has many enhancements for better readability and more detail

Technical design of the phase I Mu3e experiment

The Mu3e experiment aims to find or exclude the lepton flavour violating decay μ→eee at branching fractions above 10−16. A first phase of the experiment using an existing beamline at the Paul Scherrer Institute (PSI) is designed to reach a single event sensitivity of 2⋅10−15. We present an overview of all aspects of the technical design and expected performance of the phase I Mu3e detector. The high rate of up to 108 muon decays per second and the low momenta of the decay electrons and positrons pose a unique set of challenges, which we tackle using an ultra thin tracking detector based on high-voltage monolithic active pixel sensors combined with scintillating fibres and tiles for precise timing measurements

Models of KPTN-related disorder implicate mTOR signalling in cognitive and overgrowth phenotypes

KPTN-related disorder is an autosomal recessive disorder associated with germline variants in KPTN (previously known as kaptin), a component of the mTOR regulatory complex KICSTOR. To gain further insights into the pathogenesis of KPTN-related disorder, we analysed mouse knockout and human stem cell KPTN loss-of-function models.Kptn−/− mice display many of the key KPTN-related disorder phenotypes, including brain overgrowth, behavioural abnormalities, and cognitive deficits. By assessment of affected individuals, we have identified widespread cognitive deficits (n = 6) and postnatal onset of brain overgrowth (n = 19). By analysing head size data from their parents (n = 24), we have identified a previously unrecognized KPTN dosage-sensitivity, resulting in increased head circumference in heterozygous carriers of pathogenic KPTN variants.Molecular and structural analysis of Kptn−/− mice revealed pathological changes, including differences in brain size, shape and cell numbers primarily due to abnormal postnatal brain development. Both the mouse and differentiated induced pluripotent stem cell models of the disorder display transcriptional and biochemical evidence for altered mTOR pathway signalling, supporting the role of KPTN in regulating mTORC1.By treatment in our KPTN mouse model, we found that the increased mTOR signalling downstream of KPTN is rapamycin sensitive, highlighting possible therapeutic avenues with currently available mTOR inhibitors. These findings place KPTN-related disorder in the broader group of mTORC1-related disorders affecting brain structure, cognitive function and network integrity.Genetics of disease, diagnosis and treatmen

Biallelic loss-of-function variants in PLD1 cause congenital right-sided cardiac valve defects and neonatal cardiomyopathy

Congenital heart disease is the most common type of birth defect, accounting for one-third of all congenital anomalies. Using whole-exome sequencing of 2718 patients with congenital heart disease and a search in GeneMatcher, we identified 30 patients from 21 unrelated families of different ancestries with biallelic phospholipase D1 (PLD1) variants who presented predominantly with congenital cardiac valve defects. We also associated recessive PLD1 variants with isolated neonatal cardiomyopathy. Furthermore, we established that p.1668F is a founder variant among Ashkenazi Jews (allele frequency of -.2%) and describe the phenotypic spectrum of PLD1-associated congenital heart defects. PLD1 missense variants were overrepresented in regions of the protein critical for catalytic activity, and, correspondingly, we observed a strong reduction in enzymatic activity for most of the mutant proteins in an enzymatic assay. Finally, we demonstrate that PLD1 inhibition decreased endothelial-mesenchymal transition, an established pivotal early step in valvulogenesis. In conclusion, our study provides a more detailed understanding of disease mechanisms and phenotypic expression associated with PLD1 loss of function.Genetics of disease, diagnosis and treatmen

Primjena i kompozicija individualiziranih zaštitnih elemenata linijske grafike u projektiranju novčanica

Proces stvaranja novčanica je dugotrajan i složen, što rezultira kompleksnim rješenjima koja predstavljaju pravo remek djelo grafike. Novčanice su prožete brojnim detaljima i prenose različite informacije koje se analiziraju u teorijskom dijelu rada. Prvotno se postavljaju kriteriji po kojima se izrađuje detaljna analiza velikog broja zaštitnih i konceptualnih elemenata na primjerima novčanica. Time je prikazan okvirni povijesni pregled razvoja novčanica i utjecaji kojima je bio izložen. Analizira se međuovisnost dizajna o sigurnosnim značajkama, te se ispituje razina informiranosti javnosti o zaštitama na novčanicama. Zaključuje se koje metode zaštite su najučinkovitije, te kako šira javnost najčešće provjerava autentičnost novčanica. U eksperimentalnom dijelu rada se na temelju donesenih zaključaka iz teorijskog dijela izrađuje prototip novčanice koja je u najvećoj mjeri prožeta individualiziranim PostScript programskim rješenjima elemenata linijske grafike (rozete, mikrotekst, zaštitne linije, brojevi apoena), a od ostalih zaštita modeliran je individualizirani raster transformacijom matematičkog izraza u PostScript programski kod. Sve ostale zaštite tipične za novčanice simulirane su alatima za rastersku i vektorsku grafiku. U radu se ispituje utjecaj kompozicije zaštitnih elemenata na prepoznavanje autentičnosti novčanica, te efikasnost samih individualiziranih programskih rješenja

Integration of Cervical and Scapular Mobilization and Stabilization for a Patient with Medial Epicondylitis: A Case Report

Background and Purpose: Lee et al. discovered a correlation between cervical radiculopathy and medial epicondylitis. 1 There have been no follow up studies indicating whether one pathology leads to the others or whether treating cervical radiculopathy affects the concomitant medial epicondylitis. The purpose of this case report is to outline a treatment program for individuals with cervical radiculopathy and concomitant medial epicondylitis . Case Description: The patient was a 54 - year - old, Hispanic female who presented with complaints of right - sided, m edial elbow pain as well as grip, wrist, and elbow weakness. Upon further evaluation, the patient also presented with cervical radiculopathy. The patient did not receive any steroid injections for medial epicondylitis. Patient had significant past medical history including right shoulder adhesive capsulitis and bilateral lateral epicondylitis. Outcome Measures: The patient was assessed using the QuickDASH, pain rating via Numeric Pain Rating Scale (NPRS), strength via Manual Muscle Testing (MMT), grip stren gth via dynamometer, as well as a cervical radiculopathy cluster exam. The patient was seen for a total of 7 visits over the course of 4 weeks. Discussion: Treating concomitant cervical radiculopathy in a patient with medial epicondylitis appeared to be a safe and effective intervention program for decreasing elbow pain and improving grip strength. The presenting case report may be useful in helping clinicians determine optimal plan of care for patients with “golfers elbow”. Future randomized control trials should evaluate the relationship between cervical radiculopathy and medial epicondylitis as well as whether treating cervical radiculopathy improves patient outcomes in those with “golfers elbow”