Gemeinsame Kommunikation und Positionierung basierend auf Interleave-Division Multiplexing

Interest in joint communication and positioning is steadily increasing because the combination of both techniques offers a wide range of advantages. On the one hand, synergy effects between communication and positioning like enhanced resource allocation can be exploited. On the other hand, new applications are enabled. Examples comprise a wide area of interest and include the automated localisation of emergency calls, tracking and guiding fire fighters or policemen on a mission, monitoring people with special needs in a hospital or a nursing home, asset tracking, location-based services and so forth. However, it is a challenging task to combine communication and positioning because their prerequisites are quite different. On the one hand, high data rates with little training overhead and low bit error rate are desirable for communication. On the other hand, localisation aims at precise position estimates. Much training is typically spent for that purpose. Given a single transmit signal supporting communication as well as positioning, it is very difficult to fulfil all requirements at the same time. Hence, a flexible configuration is desirable for a joint communication and positioning system with a unified signal structure in order to adjust the tradeoff between both parts to the instantaneous needs. In this thesis, a new system concept for joint communication and positioning with a unified signal structure is proposed and investigated. The system concept is based on interleave-division multiplexing (IDM) in combination with pilot layer aided channel estimation (PLACE) and multilateration via the time of arrival (TOA). On the one hand, IDM seems to be a suitable candidate for a joint communication and positioning system because of its flexible but simple transmitter structure. On the other hand, multilateration via the TOA enables precise localisation. The connection between the communication and the positioning part is accomplished via an enhanced PLACE unit. Through the incorporation of a channel parameter estimator, not only the channel coefficients of the equivalent discrete-time channel model, that are needed for data detection, but also parameters of the physical channel, that are required for positioning, can be estimated. A priori information about pulse shaping and receive filtering is exploited for that purpose. The main aim of this thesis is to show the feasibility of the proposed joint communication and positioning system. Hence, a fundamental system setup is analysed systematically. Since many applications of joint communication and positioning are located in urban or indoor environments, a very high positioning accuracy in the centimetre region is desirable. Unfortunately, positioning is most challenging in these environments due to severe multipath propagation. In order to achieve the required accuracies, the positioning part of the proposed system concept can be complemented by other localisation sources like GPS/Galileo and/or motion sensors via sensor fusion. However, the stand-alone performance of the proposed joint communication and positioning system is evaluated by means of Monte Carlo simulations in this thesis. The achieved results are compared to performance limits in terms of Cramer-Rao lower bounds. In order to improve the overall system performance and to enable sensor fusion, soft information with respect to the parameter as well as the position estimates is taken into account. The accuracy of the soft information is analysed with the help of curvature measures. Altogether, promising results are obtained.Das Interesse an gemeinsamer Kommunikation und Positionierung nimmt aufgrund vieler Vorteile stetig zu: Durch die Kombination beider Techniken können Synergieeffekte wie beispielsweise eine verbesserte Ressourcenverteilung ausgenutzt werden. Des Weiteren werden neue Anwendungen in den unterschiedlichsten Bereichen ermöglicht: Notrufe können automatisch lokalisiert werden, Feuerwehrmänner und Polizisten im Einsatz können durch eine Verfolgung ihrer Position und gegebenenfalls eine Überwachung ihrer Vitalwerte besser angeleitet und koordiniert werden, Patienten mit speziellen Bedürfnissen in Krankenhäusern können durch ein effizientes Monitoring besser versorgt werden, Ein- und Auslagerungsprozesse in Warenhäusern können erleichtert werden, positionsbezogene Dienste können realisiert werden und vieles anderes mehr. Aufgrund der verschiedenen Anforderungen von Kommunikations- und Positionierungsdiensten ist es schwierig, diese beiden Bereiche zu vereinen. Einerseits sollen große Datenraten mit geringem Trainingsaufwand als auch geringen Bitfehlerraten erreicht werden. Andererseits ist eine hohe Positionierungsgenauigkeit erwünscht, die einen großen Trainingsaufwand erfordert. In einem Systementwurf mit einer einheitlichen Signalstruktur ist es schwer, alle Anforderungen gleichzeitig zu erfüllen. Daher ist ein flexibler Systementwurf von Vorteil, um den Abtausch zwischen Kommunikation und Positionierung an die aktuellen Bedürfnisse anpassen zu können. Im Rahmen dieser Arbeit wird ein neues gemeinsames Kommunikations- und Positionierungssystem mit einer einheitlichen Signalstruktur vorgeschlagen und untersucht. Der Systementwurf basiert auf Interleave-Division Multiplexing (IDM) in Kombination mit einer Pilotlayer basierten Kanalschätzung und Multilateration mit Hilfe der Signalankunftszeit, im Folgenden Time of Arrival (TOA) genannt. Einerseits ist IDM aufgrund seiner flexiblen, jedoch einfachen Senderstruktur gut für ein gemeinsames Kommunikations- und Positionierungssystem geeignet. Andererseits ermöglicht eine Multilateration mit Hilfe der TOA hohe Positionierungsgenauigkeiten. Die Verbindung zwischen beiden Komponenten wird durch eine erweiterte Pilotlayer basierte Kanalschätzung erreicht: Durch die Verwendung eines Kanalparameterschätzers können sowohl die Kanalkoeffizienten des äquivalenten zeitdiskreten Ersatzkanalmodells, die für die Datendetektion benötigt werden, als auch Parameter des physikalischen Kanals, die für die Lokalisierung erforderlich sind, geschätzt werden. A priori Information bezüglich des Pulsformungs- und Empfangsfilters werden hierfür ausgenutzt. Das Hauptziel dieser Arbeit ist es, die Realisierbarkeit des vorgeschlagenen gemeinsamen Kommunikations- und Positionierungssystems zu zeigen. Daher wird ein grundlegender Systementwurf systematisch analysiert. Da viele Anwendungen von gemeinsamer Kommunikation und Positionierung innerhalb von Städten oder Gebäuden angesiedelt sind, ist eine sehr hohe Positionierungsgenauigkeit im Zentimeter-Bereich wünschenswert. Unglücklicherweise ist es in diesen Gebieten aufgrund von starker Mehrwegeausbreitung besonders schwer, die Position eines Objektes zu bestimmen. Allerdings kann die Positionierungskomponente durch andere Lokalisierungsquellen wie beispielsweise GPS/Galileo und/oder Bewegungssensoren mittels Sensorfusion ergänzt werden, um die erforderlichen Genauigkeiten zu erreichen. In Rahmen dieser Arbeit wird jedoch nur die eigenständige Leistungsfähigkeit des vorgeschlagenen Systementwurfs mit Hilfe von Monte Carlo Simulationen untersucht. Die Simulationsergebnisse werden mit Leistungsgrenzen in Form von Cramer-Rao Untergrenzen verglichen. Dabei wird Zuverlässigkeitsinformation bezüglich der geschätzten Parameter und der geschätzten Position berücksichtigt, um die gesamte Systemleistung zu verbessern und Sensorfusion zu ermöglichen. Die Genauigkeit der Zuverlässigkeitsinformation wird mit Hilfe von Krümmungsmaßen analysiert. Insgesamt werden vielversprechende Ergebnisse erzielt

Structure of sulfamidase provides insight into the molecular pathology of mucopolysaccharidosis IIIA

Mucopolysaccharidosis type IIIA (Sanfilippo A syndrome), a fatal childhood-onset neurodegenerative disease with mild facial, visceral and skeletal abnormalities, is caused by an inherited deficiency of the enzyme N-sulfoglucosamine sulfohydrolase (SGSH; sulfamidase). More than 100 mutations in the SGSH gene have been found to reduce or eliminate its enzymatic activity. However, the molecular understanding of the effect of these mutations has been confined by a lack of structural data for this enzyme. Here, the crystal structure of glycosylated SGSH is presented at 2Å resolution. Despite the low sequence identity between this unique N-sulfatase and the group of O-sulfatases, they share a similar overall fold and active-site architecture, including a catalytic formylglycine, a divalent metal-binding site and a sulfate-binding site. However, a highly conserved lysine in O-sulfatases is replaced in SGSH by an arginine (Arg282) that is positioned to bind the N-linked sulfate substrate. The structure also provides insight into the diverse effects of pathogenic mutations on SGSH function in mucopolysaccharidosis type IIIA and convincing evidence for the molecular consequences of many missense mutations. Further, the molecular characterization of SGSH mutations will lay the groundwork for the development of structure-based drug design for this devastating neurodegenerative disorder. © 2014 International Union of Crystallography.This work was funded by the DFG. Partial support from DFG grant No. SH 14/5-1 is gratefully acknowledged (NSS). IU is grateful to the Spanish MEC and Generalitat de Catalunya for financial support (grants BFU2012-35367, IDC-20101173 and 2009SGR-1036)Peer Reviewe

Functional characterization of two novel 5' untranslated exons reveals a complex regulation of NOD2 protein expression

<p>Abstract</p> <p>Background</p> <p>NOD2 is an innate immune receptor for the bacterial cell wall component muramyl-dipeptide. Mutations in the leucine-rich repeat region of NOD2, which lead to an impaired recognition of muramyl-dipeptide, have been associated with Crohn disease, a human chronic inflammatory bowel disease. Tissue specific constitutive and inducible expression patterns of NOD2 have been described that result from complex regulatory events for which the molecular mechanisms are not yet fully understood.</p> <p>Results</p> <p>We have identified two novel exons of the <it>NOD2 </it>gene (designated exon 1a and 1b), which are spliced to the canonical exon 2 and constitute the 5' untranslated region of two alternative transcript isoforms (i.e. exon 1a/1b/2 and exon 1a/2). The two novel transcripts are abundantly expressed and seem to comprise the majority of NOD2 transcripts under physiological conditions. We confirm the expression of the previously known canonical first exon (designated exon 1c) of the gene in unstimulated mononuclear cells. The inclusion of the second alternative exon 1b, which harbours three short upstream open reading frames (uORFs), is downregulated upon stimulation with TNF-α or under pro-inflammatory conditions in the inflamed intestinal mucosa <it>in vivo</it>. Using the different 5' UTR splice forms fused to a firefly luciferase (LUC) reporter we demonstrate a rapamycin-sensitive inhibitory effect of the uORFs on translation efficacy.</p> <p>Conclusion</p> <p>The differential usage of two alternative promoters in the <it>NOD2 </it>gene leads to tissue-specific and context-dependent <it>NOD2 </it>transcript isoform patterns. We demonstrate for the first time that context-dependent alternative splicing is linked to uORF-mediated translational repression. The results suggest complex parallel control mechanisms that independently regulate NOD2 expression in the context of inflammatory signaling.</p

BMI, Alcohol Consumption and Gut Microbiome Species Richness Are Related to Structural and Functional Neurological Abnormalities

The incidence of neurological diseases is increasing throughout the world. The aim of the present study was to identify nutrition and microbiome factors related to structural and functional neurological abnormalities to optimize future preventive strategies. Methods: Two hundred thirty-eight patients suffering from (1) structural (neurodegeneration) or (2) functional (epilepsy) neurological abnormalities or (3) chronic pain (migraine) and 612 healthy control subjects were analyzed by validated 12-month food frequency questionnaire (FFQ) and 16S rRNA micro- biome sequencing (from stool samples). A binomial logistic regression model was applied for risk calculation and functional pathway analysis to show which functional pathway could discriminate cases and healthy controls. Results: Detailed analysis of more than 60 macro- and micronutrients revealed no distinct significant difference between cases and controls, whereas BMI, insulin resistance and metabolic inflammation in addition to alcohol consumption were major drivers of an overall neurological disease risk. The gut microbiome analysis showed decreased alpha diversity (Shannon index: p = 9.1× 10 −7 ) and species richness (p = 1.2 × 10 −8 ) in the case group as well as signifi- cant differences in beta diversity between cases and controls (Bray–Curtis: p = 9.99 × 10 −4 ; Jaccard: p = 9.99 × 10 −4 ). The Shannon index showed a beneficial effect (OR = 0.59 (95%-CI (0.40, 0.87); p = 8 × 10 −3 ). Cases were clearly discriminated from healthy controls by environmental information processing, signal transduction, two component system and membrane transport as significantly different functional pathways. Conclusions: In conclusion, our data indicate that an overall healthy lifestyle, in contrast to supplementation of single micro- or macronutrients, is most likely to reduce overall neurological abnormality risk and that the gut microbiome is an interesting target to develop novel preventive strategies

CoMet—a web server for comparative functional profiling of metagenomes

Analyzing the functional potential of newly sequenced genomes and metagenomes has become a common task in biomedical and biological research. With the advent of high-throughput sequencing technologies comparative metagenomics opens the way to elucidate the genetically determined similarities and differences of complex microbial communities. We developed the web server ‘CoMet’ (http://comet.gobics.de), which provides an easy-to-use comparative metagenomics platform that is well-suitable for the analysis of large collections of metagenomic short read data. CoMet combines the ORF finding and subsequent assignment of protein sequences to Pfam domain families with a comparative statistical analysis. Besides comprehensive tabular data files, the CoMet server also provides visually interpretable output in terms of hierarchical clustering and multi-dimensional scaling plots and thus allows a quick overview of a given set of metagenomic samples

Effect of various weight loss interventions on serum NT-proBNP concentration in severe obese subjects without clinical manifest heart failure

Obesity is associated with a "natriuretic handicap" indicated by reduced N-terminal fragment of proBNP (NT-proBNP) concentration. While gastric bypass surgery improves the natriuretic handicap, it is presently unclear if sleeve gastrectomy exhibits similar effects. We examined NT-proBNP serum concentration in n = 72 obese participants without heart failure before and 6 months after sleeve gastrectomy (n = 28), gastric bypass surgery (n = 19), and 3-month 800 kcal/day very-low calorie diet (n = 25). A significant weight loss was observed in all intervention groups. Within 6 months, NT-proBNP concentration tended to increase by a median of 44.3 pg/mL in the sleeve gastrectomy group (p = 0.07), while it remained unchanged in the other groups (all p ≥ 0.50). To gain insights into potential effectors, we additionally analyzed NT-proBNP serum concentration in n = 387 individuals with different metabolic phenotypes. Here, higher NT-proBNP levels were associated with lower nutritional fat and protein but not with carbohydrate intake. Of interest, NT-proBNP serum concentrations were inversely correlated with fasting glucose concentration in euglycemic individuals but not in individuals with prediabetes or type 2 diabetes. In conclusion, sleeve gastrectomy tended to increase NT-proBNP levels in obese individuals and might improve the obesity-associated "natriuretic handicap". Thereby, nutritional fat and protein intake and the individual glucose homeostasis might be metabolic determinants of NT-proBNP serum concentration

Human Neurospheres as Three-Dimensional Cellular Systems for Developmental Neurotoxicity Testing

Bac k g r o u n d: Developmental neurotoxicity (DNT) of environmental chemicals is a serious threat to human health. Current DNT testing guidelines propose investigations in rodents, which require large numbers of animals. With regard to the “3 Rs ” (reduction, replacement, and refinement) of animal testing and the European regulation of chemicals [Registration, Evaluation, and Authorisation of Chemicals (REACH)], alternative testing strategies are needed in order to refine and reduce animal experiments and allow faster and less expensive screening. Objectives: The goal of this study was to establish a three-dimensional test system for DNT screening based on human fetal brain cells. Met h o d s: We established assays suitable for detecting disturbances in basic processes of brain development by employing human neural progenitor cells (hNPCs), which grow as neurospheres. Furthermore, we assessed effects of mercury and oxidative stress on these cells. Re s u l t s: We found that human neurospheres imitate proliferation, differentiation, and migration in vitro. Exposure to the proapoptotic agent staurosporine further suggests that human neurospheres possess functioning apoptosis machinery. The developmental neurotoxicants methylmercury chloride and mercury chloride decreased migration distance and number of neuronal-like cells in differentiated hNPCs. Furthermore, hNPCs undergo caspase-independent apoptosis when exposed toward high amounts of oxidative stress. Co n c l u s i o n s: Human neurospheres are likely to imitate basic processes of brain development, and these processes can be modulated by developmental neurotoxicants. Thus, this three-dimensional cell system is a promising approach for DNT testing. Key w o r d s: apoptosis, differentiation, DNT, human neurospheres, mercury, migration, proliferation. Environ Health Perspect 117:1131–1138 (2009). doi:10.1289/ehp.0800207 available vi

Brief Research Report: Serum clara cell 16 kDa protein levels are increased in patients hospitalized for severe SARS-CoV-2 or sepsis infection

Background Clara cell 16 kDa protein (CC16) is a secretory protein primarily expressed in epithelial cells in the lungs. Previous studies show that CC16 exerts anti-inflammatory and immune-modulatory properties in both acute and chronic pulmonary diseases. However, despite the evidence of CC16's high biomarker potential, evaluation of its role in infectious diseases is yet very limited. Methods Serum CC16 concentrations were measured by ELISA and assessed in two different types of severe infections. Using a case-control study design, patients treated for either severe SARS-CoV-2 or severe non-pulmonary sepsis infection were compared to age- and sex-matched healthy human subjects. Results Serum CC16 was significantly increased in both types of infection (SARS-CoV-2: 96.22 ± 129.01 ng/ml vs. healthy controls: 14.05 ± 7.48 ng/ml, p = 0.022; sepsis: 35.37 ± 28.10 ng/ml vs. healthy controls: 15.25 ± 7.51 ng/ml, p = 0.032) but there were no distinct differences between infections with and without pulmonary focus (p = 0.089). Furthermore, CC16 serum levels were positively correlated to disease duration and inversely to the platelet count in severe SARS-CoV-2 infection. Conclusions Increased CC16 serum levels in both SARS-CoV-2 and sepsis reinforce the high potential as a biomarker for epithelial cell damage and bronchoalveolar-blood barrier leakage in pulmonary as well as non-pulmonary infectious diseases