Planck pre-launch status: calibration of the Low Frequency Instrument flight model radiometers

The Low Frequency Instrument (LFI) on-board the ESA Planck satellite carries eleven radiometer subsystems, called Radiometer Chain Assemblies (RCAs), each composed of a pair of pseudo-correlation receivers. We describe the on-ground calibration campaign performed to qualify the flight model RCAs and to measure their pre-launch performances. Each RCA was calibrated in a dedicated flight-like cryogenic environment with the radiometer front-end cooled to 20K and the back-end at 300K, and with an external input load cooled to 4K. A matched load simulating a blackbody at different temperatures was placed in front of the sky horn to derive basic radiometer properties such as noise temperature, gain, and noise performance, e.g. 1/f noise. The spectral response of each detector was measured as was their susceptibility to thermal variation. All eleven LFI RCAs were calibrated. Instrumental parameters measured in these tests, such as noise temperature, bandwidth, radiometer isolation, and linearity, provide essential inputs to the Planck-LFI data analysis.Comment: 15 pages, 18 figures. Accepted for publication in Astronomy and Astrophysic

Multiscale Cohort Modeling of Atrial Electrophysiology : Risk Stratification for Atrial Fibrillation through Machine Learning on Electrocardiograms

Patienten mit Vorhofflimmern sind einem fünffach erhöhten Risiko für einen ischämischen Schlaganfall ausgesetzt. Eine frühzeitige Erkennung und Diagnose der Arrhythmie würde ein rechtzeitiges Eingreifen ermöglichen, um möglicherweise auftretende Begleiterkrankungen zu verhindern. Eine Vergrößerung des linken Vorhofs sowie fibrotisches Vorhofgewebe sind Risikomarker für Vorhofflimmern, da sie die notwendigen Voraussetzungen für die Aufrechterhaltung der chaotischen elektrischen Depolarisation im Vorhof erfüllen. Mithilfe von Techniken des maschinellen Lernens könnten Fibrose und eine Vergrößerung des linken Vorhofs basierend auf P Wellen des 12-Kanal Elektrokardiogramms im Sinusrhythmus automatisiert identifiziert werden. Dies könnte die Basis für eine nicht-invasive Risikostrat- ifizierung neu auftretender Vorhofflimmerepisoden bilden, um anfällige Patienten für ein präventives Screening auszuwählen. Zu diesem Zweck wurde untersucht, ob simulierte Vorhof-Elektrokardiogrammdaten, die dem klinischen Trainingssatz eines maschinellen Lernmodells hinzugefügt wurden, zu einer verbesserten Klassifizierung der oben genannten Krankheiten bei klinischen Daten beitra- gen könnten. Zwei virtuelle Kohorten, die durch anatomische und funktionelle Variabilität gekennzeichnet sind, wurden generiert und dienten als Grundlage für die Simulation großer P Wellen-Datensätze mit genau bestimmbaren Annotationen der zugrunde liegenden Patholo- gie. Auf diese Weise erfüllen die simulierten Daten die notwendigen Voraussetzungen für die Entwicklung eines Algorithmus für maschinelles Lernen, was sie von klinischen Daten unterscheidet, die normalerweise nicht in großer Zahl und in gleichmäßig verteilten Klassen vorliegen und deren Annotationen möglicherweise durch unzureichende Expertenannotierung beeinträchtigt sind. Für die Schätzung des Volumenanteils von linksatrialem fibrotischen Gewebe wurde ein merkmalsbasiertes neuronales Netz entwickelt. Im Vergleich zum Training des Modells mit nur klinischen Daten, führte das Training mit einem hybriden Datensatz zu einer Reduzierung des Fehlers von durchschnittlich 17,5 % fibrotischem Volumen auf 16,5 %, ausgewertet auf einem rein klinischen Testsatz. Ein Long Short-Term Memory Netzwerk, das für die Unterscheidung zwischen gesunden und P Wellen von vergrößerten linken Vorhöfen entwickelt wurde, lieferte eine Genauigkeit von 0,95 wenn es auf einem hybriden Datensatz trainiert wurde, von 0,91 wenn es nur auf klinischen Daten trainiert wurde, die alle mit 100 % Sicherheit annotiert wurden, und von 0,83 wenn es auf einem klinischen Datensatz trainiert wurde, der alle Signale unabhängig von der Sicherheit der Expertenannotation enthielt. In Anbetracht der Ergebnisse dieser Arbeit können Elektrokardiogrammdaten, die aus elektrophysiologischer Modellierung und Simulationen an virtuellen Patientenkohorten resul- tieren und relevante Variabilitätsaspekte abdecken, die mit realen Beobachtungen übereinstim- men, eine wertvolle Datenquelle zur Verbesserung der automatisierten Risikostratifizierung von Vorhofflimmern sein. Auf diese Weise kann den Nachteilen klinischer Datensätze für die Entwicklung von Modellen des maschinellen Lernens entgegengewirkt werden. Dies trägt letztendlich zu einer frühzeitigen Erkennung der Arrhythmie bei, was eine rechtzeitige Auswahl geeigneter Behandlungsstrategien ermöglicht und somit das Schlaganfallrisiko der betroffenen Patienten verringert

Design and analysis of highspeed electronics for electro optical payload of small satellites

With the increase in the resolution of the Earth observation satellites, the cameras on these satellites require more detectors to fulfil the swath need and also the image sensors have to operate at a very high-speed with the sensor electronics requiring faster clock rates and larger bandwidth. The sensor data handler has to transfer a large amount of data to the spacecraft in real time incorporating the outcomes of the signal integrity and power integrity analysis in the design. High-speed analysis is an important consideration for high resolution cameras and is often performed on the satellites. This research work aims towards presenting the design and analysis of high-speed electronics for small Earth observation satellites. A methodology will be defined for the designing of high-speed electronics that will involve both the pre-layout and post-layout designs for signal and power integrity analysis. The proposed research work also provides the pre-layout and post-layout signal integrity analysis of the high-speed electronics and interfaces and it will also validate the signal integrity performance of the module by comparing it with standard performance parameters. Similarly, we will perform a pre-layout and post-layout power integrity analysis of the high-speed electronics and interfaces and its effects on the power lines and power planes

Simulation of Conformal Spiral Slot Antennas on Composite Platforms

During the course of the grant, we wrote and distributed about 12 reports and an equal number of journal papers supported fully or in part by this grant. The list of reports (title & abstract) and papers are given in Appendices A and B. This grant has indeed been instrumental in developing a robust hybrid finite element method for the analysis of complex broadband antennas on doubly curved platforms. Previous to the grant, our capability was limited to simple printed patch antennas on mostly planar platforms. More specifically: (1) mixed element formulations were developed and new edge-based prisms were introduced; (2) these elements were important in permitting flexibility in geometry gridding for most antennas of interest; (3) new perfectly matched absorbers were introduced for mesh truncations associated with highly curved surfaces; (4) fast integral algorithms were introduced for boundary integral truncations reducing CPU time from O(N-2) down to O(N-1.5) or less; (5) frequency extrapolation schemes were developed for efficient broadband performance evaluations. This activity has been successfully continued by NASA researchers; (6) computer codes were developed and extensively tested for several broadband configurations. These include FEMA-CYL, FEMA-PRISM and FEMA-TETRA written by L. Kempel, T. Ozdemir and J. Gong, respectively; (7) a new infinite balun feed was designed nearly constant impedance over the 800-3000 MHz operational band; (8) a complete slot spiral antenna was developed, fabricated and tested at NASA Langley. This new design is a culmination of the projects goals and integrates the computational and experimental efforts. this antenna design resulted in a U.S. patent and was revised three times to achieve the desired bandwidth and gain requirements from 800-3000 MHz

I/O port macromodelling

3D electromagnetic modelling and simulation of various Printed Circuit Board (PCB) components is an important technique for characterizing the Signal Integrity (SI) and Electromagnetic Compatibility (EMC) issues present in a PCB. However, due to limited computational resource and the complexity of the integrated circuits, it is currently not possible to fully model a complete PCB system with 3D electromagnetic solvers. An effort has been made to fully model the PCB with all its components and their S-parameters has been derived so as to integrate these S-parameters in 1D, 2D static or quasi-static field solver or circuit solver tool. The novelty of this thesis is the development and verification of active circuit such as Input and Output buffers and passive channel components such as interconnects, via and connectors and deriving their S-parameters in order to model and characterize the complete PCB using 3D full field solver based on Transmission Line Matrix modelling (TLM) method. An integration of Input/Output (I/O) port in the 3D full field modelling method allows for modelling of the complete PCB system without being computationally expensive. This thesis presents a method for integration of Input/Output port in the 3D time domain modelling environment. Several software tools are available in the market which can characterize these PCBs in the frequency as well as the time domain using 1D, 2D techniques or using circuit solver such as spice. The work in this thesis looks at extending these 1D and 2D techniques for 3D Electromagnetic solvers in the time domain using the TLM technique for PCB analysis. The modelling technique presented in this thesis is based on in-house developed 3D TLM method along with a developed behavioral Integrated Circuit (IC) – macromodel. The method has been applied to a wide variety of PCB topologies along with a range of IC packages to fully validate the approach. The method has also been applied to show the switching effect arising out of the crosstalk in a logic device apart from modelling various discontinuities of PCB interconnects in the form of S11 and S21 parameters. The proposed novel TLM based technique has been selected based on simplification of its approach, electrical equivalence (rather than complex mathematical functions of Maxwell's electromagnetic theory), time domain analysis for transients in a PCB with an increased accuracy over other available methods in the literature. On the experimental side two, four and six layered PCBs with various interconnect discontinuities such as straight line, right angle, fan-out and via and IC packages such as SOT-23 (DBV), SC-70 (DCK) and SOT-553 (DRL) has been designed and manufactured. The modelling results have been verified with the experimental results of these PCBs and other commercial software such as HSPICE, CST design studio available in the market. While characterizing the SI issues, these modelling results can also help in analyzing conducted and radiated EMC/EMI problems to meet various EMC regulations such as CE, FCC around the world

I/O port macromodelling

3D electromagnetic modelling and simulation of various Printed Circuit Board (PCB) components is an important technique for characterizing the Signal Integrity (SI) and Electromagnetic Compatibility (EMC) issues present in a PCB. However, due to limited computational resource and the complexity of the integrated circuits, it is currently not possible to fully model a complete PCB system with 3D electromagnetic solvers. An effort has been made to fully model the PCB with all its components and their S-parameters has been derived so as to integrate these S-parameters in 1D, 2D static or quasi-static field solver or circuit solver tool. The novelty of this thesis is the development and verification of active circuit such as Input and Output buffers and passive channel components such as interconnects, via and connectors and deriving their S-parameters in order to model and characterize the complete PCB using 3D full field solver based on Transmission Line Matrix modelling (TLM) method. An integration of Input/Output (I/O) port in the 3D full field modelling method allows for modelling of the complete PCB system without being computationally expensive. This thesis presents a method for integration of Input/Output port in the 3D time domain modelling environment. Several software tools are available in the market which can characterize these PCBs in the frequency as well as the time domain using 1D, 2D techniques or using circuit solver such as spice. The work in this thesis looks at extending these 1D and 2D techniques for 3D Electromagnetic solvers in the time domain using the TLM technique for PCB analysis. The modelling technique presented in this thesis is based on in-house developed 3D TLM method along with a developed behavioral Integrated Circuit (IC) – macromodel. The method has been applied to a wide variety of PCB topologies along with a range of IC packages to fully validate the approach. The method has also been applied to show the switching effect arising out of the crosstalk in a logic device apart from modelling various discontinuities of PCB interconnects in the form of S11 and S21 parameters. The proposed novel TLM based technique has been selected based on simplification of its approach, electrical equivalence (rather than complex mathematical functions of Maxwell's electromagnetic theory), time domain analysis for transients in a PCB with an increased accuracy over other available methods in the literature. On the experimental side two, four and six layered PCBs with various interconnect discontinuities such as straight line, right angle, fan-out and via and IC packages such as SOT-23 (DBV), SC-70 (DCK) and SOT-553 (DRL) has been designed and manufactured. The modelling results have been verified with the experimental results of these PCBs and other commercial software such as HSPICE, CST design studio available in the market. While characterizing the SI issues, these modelling results can also help in analyzing conducted and radiated EMC/EMI problems to meet various EMC regulations such as CE, FCC around the world

ADVANCED STUDIES ON SERIES IMPEDANCE IN WAVEGUIDES WITH AN EMPHASIS ON SOURCE AND TRANSFER IMPEDANCE

Series impedances, including source and transfer impedances, are commonly used to model a variety of noise sources and noise treatment elements in duct systems. Particle velocity is assumed to be constant on the plane where the series impedances are defined. The research reported herein details investigations into measuring source and transfer impedance. Especially, the measurement and prediction of the transfer impedance of micro-perforated panel (MPP) absorbers is considered. A wave decomposition method for measuring source impedance and source strength was developed that was purely based on acoustic concepts instead of the equivalent circuit analysis. The method developed is a two-load method. However, it is not necessary to know the impedances of either load a priori. The selection of proper loads was investigated via an error analysis, and the results suggested that it was best to choose one resistive and one reactive load. In addition, a novel type of perforated element was investigated. MPP absorbers are metal or plastic panels with sub-millimeter size holes or slits. In the past, Maa\u27s equation has been used to characterize their performance. However, Maa\u27s equation is only valid for circular perforations. In this research, an inverse method using a nonlinear least square data fitting algorithm was developed to estimate effective parameters that could be used in Maa\u27s theory. This inverse approach was also used to aid in understanding the effect of dust and fluid contamination on the performance of MPP absorbers. In addition, an approach to enhance the attenuation of MPP absorbers by partitioning the backing cavity was investigated experimentally and numerically. Results indicated that partitioning improved the attenuating of grazing sound waves. The effect of modifying both the source and transfer impedances on the system response was also studied using the Moebius transformation. It was demonstrated that the Moebius transformation is a mathematical tool that can be employed to aid in determining and understanding the impact of acoustic impedance modifications on a vibro-acoustic system

Characterization of mRNA dysfunctional mechanisms associated with the genetic disease cystic fibrosis

Tese de doutoramento, Bioquímica (Genética Molecular), Universidade de Lisboa, Faculdade de Ciências, 2018Cystic Fibrosis (CF) is the most common autosomal disease in Caucasians, with an estimated incidence of 1:6000 births in Portugal. The most relevant clinical aspect of its classic manifestation is chronic lung disease, which is the main cause of morbidity and mortality. Other symptoms include, pancreatic dysfunction, male infertility and high concentrations of chloride (Cl-) in sweat. However, even though the classic form of the disease is well defined, its pathophysiology is not completely understood with this pleiotropic disease having highly variable manifestations of clinical phenotypes. Novel therapies aim to correct the basic defect, specifically focusing on the rescue of Cystic fibrosis transmembrane conductance regulator (CFTR) function in CF airways. Most of these CFTR modulator strategies target the F508del, the most common mutation. Nevertheless, widespread evidence has demonstrated that a significant number of CFcausing mutations affect splicing efficiency and the stability of mRNA molecules. Here, we propose to elucidate the regulatory mechanisms underlying these CF-associated mutations. To this end, our aims are: 1) to identify CFTR gene mutations in individuals with non-CF chronic lung diseases, namely chronic obstructive pulmonary disease (COPD), asthma and disseminated bronchiectasis (DB); 2) to identify CFTR gene mutations in individuals with a suspicion of CF, followed by the analysis of CFTR expression in their native tissues to characterize the impact of CFTR splicing or premature termination codon (PTC) mutations in the structure and levels of mRNA; 3) to identify key factors in the nonsense/mediated decay (NMD) pathway by automated microscopy screens using a cell model expressing a novel CFTR NMD-PTC/read-through mini-gene reporter; and 4) to screen for novel compounds suppressing PTC mutations by automated microscopy screens using the previous cell-based model, as potential corrective therapies for CF. The expected results will provide knowledge on RNA-processing dysfunction and on the efficacy of novel RNA modulator compounds towards a "personalised medicine" approach. Regarding the first objective, our data show that 7 (out of 136) patients with non-CF respiratory diseases presented CFTR mutations in one allele, in contrast with the control group, in which no mutations were detected. We analysed the association of CFTR gene mutations with each of the three respiratory diseases considered. For asthma our data did not show an increase in mutation frequency when compared to the control group. For DB, we found an increase in the frequency of CFTR gene mutations, albeit with no statistical significance, which is in agreement with previous reports. For COPD however, we found a statistically significant increase in CFTR gene mutation incidence, relative to the control group. Our data reinforce the importance of characterizing CFTR gene mutations on non-CF respiratory diseases in Portuguese patients, to gain a better understanding of the epidemiology and etiology of these diseases. The results also lead to the identification of groups of patients who may benefit from the new therapeutic compounds currently under development to correct the basic CFTR protein defect in CF. Concerning the second objective, we have developed a novel RNA-based approach to detect unknown CFTR mutations [Felício et al (2017) Clin Genet 91: 476-481]. We are currently using this protocol for patients with a suspicion of CF and none or just one CFTR mutation identified. With this method we identified one mutation (711+3A>T) which had been previously reported but had not been characterized. We can conclude that this is a rapid, robust and inexpensive method to detect rare mutations, and therefore a method that can be easily used after a first screen. Regarding the third objective, we used this CFTR-NMD reporter to identify novel NMD factors by screening a previously validated shRNA library – a subset of The RNAi Consortium (TRC) – which is enriched in shRNAs targeting genes with a known or predicted involvement in transcript processing (425 genes), using HT microscopy. We selected the 24 top hits for the confirmation: 11 genes with NMD score ≥ 2 and more than 2 shRNAs with the same phenotype; 2 genes from the screen that showed read-through activity; and 11 other genes resulting from a high-throughput screen (HTS) aimed at the identification of CFTR splicing regulators (unpublished data). We chose these genes related to splicing because this is a process known to be required for NMD to occur and thus the knock-down of such genes can lead to NMD inhibition. The confirmation screen was performed using a library of siRNAs targeting the previously selected genes, however the results were inconclusive due to the low NMD score obtained. We have identified 4 genes with higher values but NMD score ≤ 1, three (eIF4A3, SREK1 and RPS19) are related to splicing, elF4A3 is directly and RPS19 is indirectly related to NMD, SREK1 is related only to splicing, with the fourth gene, ADIRF, having unknown functional properties. Some of the hits identified within this screen may be potential drug targets by their effects in inhibiting NMD, when knocked-down. With the results obtained in the confirmation screen we decided to follow the 24 genes identified in the primary screen for validation studies using two different techniques: WB and qRT-PCR (study in progress). Lastly, the fourth objective was to restore functional protein production to PTC mutations using read-through compounds, with the ultimate aim of CF patient treatment. The CFTRNMD construct used has the G542X nonsense mutation, mCherry at the N terminus and eGFP fused at the CFTR C-terminus. Through the screen of the library, we identified new small-molecule compounds that induced PTC read-through. To confirm the read-through efficiency future experiments are needed using additional techniques, such as, WB and transcript analysis by semi-quantitative PCR and qRT-PCR. Finally, to validate the top hit compounds, it is necessary to test them in patient’s materials, including nasal primary cells for functional activity and intestinal organoids to determine a dose response and to test these compounds in combination with potentiators and correctors. The studies presented in this dissertation had the overall aims of advancing the current knowledge on RNA-processing dysfunction and of identifying novel RNA modulator compounds towards a "personalised medicine" approach. The results obtained have indeed provided new insights into: 1) the relationship of other respiratory diseases with the presence of CFTR mutations; 2) new approaches to detect CFTR mutations in DNA and RNA; and 3) our understanding of key factors in NMD and read-through activity in relation to CFTR nonsense mutations