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Sabine Beate Reustle, Stift und Stadt Backnang im 16. Jahrhundert. Territorialisierung und Reformation in einer württembergischen Amtsstadt (Backnanger Forschungen, Bd. 2), Backnang (Fr. Stroh) 1996. 375 S„ 15 Abb., 2 Karten, 5 Schaubilder, 20 Tab.

Von Papsttöchtern, Bettelreisenden, Revolutionären und anderen Menschen in unserer Stadt, hrsg. vom Stadtarchiv Winnenden (Winnenden, gestern und heute, Bd. 7), Ubstadt-Weiher (Verl. Regionalkultur), 1999. 230 S.

Tropical cyclones drive coastal ecosystem dynamics, and their frequency, intensity, and spatial distribution are predicted to shift with climate change. Patterns of resistance and resilience were synthesized for 4138 ecosystem time series from n = 26 storms occurring between 1985 and 2018 in the Northern Hemisphere to predict how coastal ecosystems will respond to future disturbance regimes. Data were grouped by ecosystems (fresh water, salt water, terrestrial, and wetland) and response categories (biogeochemistry, hydrography, mobile biota, sedentary fauna, and vascular plants). We observed a repeated pattern of trade-offs between resistance and resilience across analyses. These patterns are likely the outcomes of evolutionary adaptation, they conform to disturbance theories, and they indicate that consistent rules may govern ecosystem susceptibility to tropical cyclones.

Ultra-high-energy neutrinos serve as messengers of some of the highest energy astrophysical environments. Given that neutrinos are neutral and only interact via weak interactions, neutrinos can emerge from sources, traverse astronomical distances, and point back to their origins. Their weak interactions require large target volumes for neutrino detection. Using the Earth as a neutrino converter, terrestrial, sub-orbital, and satellite-based instruments are able to detect signals of neutrino-induced extensive air showers. In this paper, we describe the software code $\texttt{nuPyProp}$ that simulates tau neutrino and muon neutrino interactions in the Earth and predicts the spectrum of the $\tau$-lepton and muons that emerge. The $\texttt{nuPyProp}$ outputs are lookup tables of charged lepton exit probabilities and energies that can be used directly or as inputs to the $\texttt{nuSpaceSim}$ code designed to simulate optical and radio signals from extensive air showers induced by the emerging charged leptons. We describe the inputs to the code, demonstrate its flexibility and show selected results for $\tau$-lepton and muon exit probabilities and energy distributions. The $\texttt{nuPyProp}$ code is open source, available on Github., Comment: 42 pages, 21 figures, fixed typo in one of the author's name. Code available at https://github.com/NuSpaceSim/nupyprop

Winnenden – gestern und heute, Geschichten über die Stadtgründung, die Stadtkirche und einen Ehrenbürger, Schriftleitung Sabine Beate Reustle (Veröffentlichungen des Stadtarchivs 14), Ubstadt-Weiher: verlag regionalkultur 2013. 232 S. ISBN 978-3-89735-799-0.€ 16,80

An accurate modeling of neutrino flux attenuation and the distribution of leptons they produce in transit through the Earth is an essential component to determine neutrino flux sensitivities of underground, sub-orbital and space-based detectors. Through neutrino oscillations over cosmic distances, astrophysical neutrino sources are expected to produce nearly equal fluxes of electron, muon and tau neutrinos. Of particular interest are tau neutrinos that interact in the Earth at modest slant depths to produce $\tau$-leptons. Some $\tau$-leptons emerge from the Earth and decay in the atmosphere to produce extensive air showers. Future balloon-borne and satellite-based optical Cherenkov neutrino telescopes will be sensitive to upward air showers from tau neutrino induced $\tau$-lepton decays. We present nuPyProp, a python code that is part of the nuSpaceSim package. nuPyProp generates look-up tables for exit probabilities and energy distributions for $\nu_\tau\to \tau$ and $\nu_\mu\to \mu$ propagation in the Earth. This flexible code runs with either stochastic or continuous electromagnetic energy losses for the lepton transit through the Earth. Current neutrino cross section models and energy loss models are included along with templates for user input of other models. Results from nuPyProp are compared with other recent simulation packages for neutrino and charged lepton propagation. Sources of modeling uncertainties are described and quantified., Comment: 9 pages, 6 figures, PoS(ICRC2021)1203; for associated code, see https://github.com/NuSpaceSim/nupyprop

Summary Marine ecosystems face numerous challenges from natural and anthropogenic sources. For example, excessive rainfall from storms rapidly lowers salinity, which can destroy coastal foundation species and their associated fauna [ 1 ], while fishing can alter coastal food webs, reduce biodiversity, and lower ecosystem resilience [ 2 ]. Concurrently, mass disruptions to fishing activity are common following disasters such as hurricanes, oil spills, and tsunamis, which may lead to increased populations of harvested species [ 3 ]. However, our understanding of how these disturbances interact to affect communities remains limited. We examined effects on estuarine communities following fishing disruptions and salinity changes caused by a tropical cyclone. Our results indicate that recreational fishing had large effects on fish populations that cascaded down the food web. Further, although destructive, hurricanes and other disturbances that simultaneously curtail human activities may promote recovery. Video Abstract Download : Download video (62MB)

Additional file 2. Contains supplementary tables Tab. S2-S10 and supplementary figures Fig. S1-S7.

The efflux transporter breast cancer resistance protein BCRP/ABCG2 is well-known for its contribution to multi-drug resistance in cancer. Its relevance in cancer biology independent from drug efflux remains largely elusive. Our study aimed at elucidating the biological relevance and regulatory mechanisms of BCRP/ABCG2 in clear cell renal cell carcinoma (ccRCC) and disease progression. Two independent ccRCC-cohorts [Cohort 1 (KIRC/TCGA): n = 453, Cohort 2: n = 64] were investigated to elucidate BCRP/ABCG2 mRNA and protein expression and their association with survival. The impact of BCRP/ABCG2 on response to sunitinib treatment was investigated in two independent sunitinib-treated ccRCC-cohorts based on mRNA levels. Moreover, underlying regulatory mechanisms for interindividual variability of BCRP/ABCG2 expression were systematically assessed. Owing to redundant functional properties, mRNA and protein expression of the multidrug resistance protein MDR1/ABCB1 were additionally evaluated in these cohorts. In independent ccRCC-cohorts, low BCRP/ABCG2 and MDR1/ABCB1 mRNA and protein expression were associated with severity (e.g., tumor stage) of ccRCC and poor cancer-specific survival. BCRP/ABCG2 and MDR1/ABCB1 mRNA expression were linked to decreased progression-free survival after sunitinib treatment. Germline and somatic variants influenced interindividual variability of BCRP/ABCG2 expression only moderately. miR-212-3p and miR-132-3p were identified to regulate BCRP/ABCG2 posttranscriptionally by interaction with the ABCG2 3'UTR as confirmed through reporter gene assays in RCC cell lines. In summary, BCRP/ABCG2 expression in ccRCC underlies considerable interindividual variability with impact on patient survival and response to sunitinib treatment. While germline or somatic genetic variants and DNA methylation cannot explain aberrant BCRP/ABCG2 expression, miR-212-3p and miR-132-3p were identified to contribute to posttranscriptional regulation of BCRP/ABCG2.

Chronic kidney disease (CKD) is a global health problem that affects around 11 to 13% of the world’s population and more than 18% of European citizens. Characteristic syndromes of CKD during all stages of the disease are proteinuria and ongoing glomerular dysfunction caused by cellular damages at the glomerular filtration barrier. While some rare cases of the disease are correlated to genetic depositions the majority of cases are caused by diabetes, glomerulosclerosis, high blood pressure and glomerulonephritis. Thus, recapitulating the interplay of high blood pressure and changes at the glomerular filtration barrier in vitro seems an adequate way to mimic CKD. Here we present a microphysiological system of the glomerular filter that is capable to simulate high blood pressure at the glomerular filtration barrier in vitro. It consists of a closed loop microfluidic circuit with an integrated pneumatically driven heart like micro pump that constantly circulates the cell culture media at the blood site of the glomerular barrier. The ThinCert™ insert could be reversibly integrated into a holder system that ensures the correct position of the insert within the microfluidic circuit. By using different modulations of the integrated pneumatic micro pump different physiological and pathophysiological conditions e.g. hypertonic stress, like in CKD, could be applied. The influence of hypertonic conditions on the filtration above the barrier was studied by changes of TEER values and measurement of the flux of fluorescent labelled albumin through the cellular barrier.

In this paper the design and measurement verification of optimized planar sparse arrays for use in wireless localization applications are presented. Existing literature on array optimization has mainly been concerned with arrays intended for imaging applications. As the array requirements for 3-D localization in multipath environments are essentially different, we made an analysis of the array parameters important for this specific application. The set of challenging practically relevant requirements for the optimization of the planar array layout was defined, including a restriction to a small number of antennas and minimal interelement distance bigger than $\lambda /2$ . An adapted multi-objective particle swarm optimization stochastic algorithm was employed to optimize array for the robust and precise direction of arrival of a single source inside a wide angular scan range up to ±60° in azimuth and elevation planes. Two optimized receive arrays consisting of eight patches were manufactured and measured to present the trade-off achieved under the desired requirements. The effects of optimized array parameters on the performance of 3-D positioning are validated by angle measurements in an anechoic chamber and different indoor scenarios.

In the post-genomic era, increasingly sophisticated genetic tools are being developed with the long-term goal of understanding how the coordinated activity of genes gives rise to a complex organism. With the advent of the next generation sequencing associated with effective computational approaches, wide variety of plant species have been fully sequenced giving a wealth of data sequence information on structure and organization of plant genomes. Since thousands of gene sequences are already known, recently developed functional genomics approaches provide powerful tools to analyze plant gene functions through various gene manipulation technologies. Integration of different omics platforms along with gene annotation and computational analysis may elucidate a complete view in a system biology level. Extensive investigations on reverse genetics methodologies were deployed for assigning biological function to a specific gene or gene product. We provide here an updated overview of these high throughout strategies highlighting recent advances in the knowledge of functional genomics in plants.

Background Clear cell renal cell carcinoma (ccRCC) is the dominant subtype of renal cancer. With currently available therapies, cure of advanced and metastatic ccRCC is achieved only in rare cases. Here, we developed a workflow integrating different -omics technologies to identify ccRCC-specific HLA-presented peptides as potential drug targets for ccRCC immunotherapy. Methods We analyzed HLA-presented peptides by MS-based ligandomics of 55 ccRCC tumors (cohort 1), paired non-tumor renal tissues, and 158 benign tissues from other organs. Pathways enriched in ccRCC compared to its cell type of origin were identified by transcriptome and gene set enrichment analyses in 51 tumor tissues of the same cohort. To retrieve a list of candidate targets with involvement in ccRCC pathogenesis, ccRCC-specific pathway genes were intersected with the source genes of tumor-exclusive peptides. The candidates were validated in an independent cohort from The Cancer Genome Atlas (TCGA KIRC, n = 452). DNA methylation (TCGA KIRC, n = 273), somatic mutations (TCGA KIRC, n = 392), and gene ontology (GO) and correlations with tumor metabolites (cohort 1, n = 30) and immune-oncological markers (cohort 1, n = 37) were analyzed to characterize regulatory and functional involvements. CD8+ T cell priming assays were used to identify immunogenic peptides. The candidate gene EGLN3 was functionally investigated in cell culture. Results A total of 34,226 HLA class I- and 19,325 class II-presented peptides were identified in ccRCC tissue, of which 443 class I and 203 class II peptides were ccRCC-specific and presented in ≥ 3 tumors. One hundred eighty-five of the 499 corresponding source genes were involved in pathways activated by ccRCC tumors. After validation in the independent cohort from TCGA, 113 final candidate genes remained. Candidates were involved in extracellular matrix organization, hypoxic signaling, immune processes, and others. Nine of the 12 peptides assessed by immunogenicity analysis were able to activate naïve CD8+ T cells, including peptides derived from EGLN3. Functional analysis of EGLN3 revealed possible tumor-promoting functions. Conclusions Integration of HLA ligandomics, transcriptomics, genetic, and epigenetic data leads to the identification of novel functionally relevant therapeutic targets for ccRCC immunotherapy. Validation of the identified targets is recommended to expand the treatment landscape of ccRCC.

We describe a new comprehensive, end-to-end simulation package for the modeling of the extensive air shower (EAS) signals from very-high energy (above a PeV) cosmic neutrinos applicable to sub-orbital and space-based observations. The goal is to provide an efficient and practical cosmic neutrino EAS signal generation modeling package to the community that will provide a standard to gauge the neutrino measurement performance of these experiments and aid in their development. The modeling will be performed in such a way to easily be used to provide the neutrino-induced EAS signals delivered to a specific altitude for a given instrumental field-of-view and orientation. In this paper, we discuss the modeling of tau neutrino interactions inside the Earth, propagating the tau-leptons into the atmosphere, modeling the decays, forming composite EASs, generating the air fluorescence, Cherenkov, and radio signals, and the propagation through the atmosphere. Future work on the modeling of atmospheric transmission and scattering effects will include consideration of the uncertainties and more robust modeling of atmospheric and UHECR backgrounds. Additionally, the framework will allow for the calculation of the sky coverage, the pointing requirements for target-of-opportunity follow up observations of transients, and the inclusion of different neutrino interaction cross-sections to allow for the modeling of non-standard physical processes.

The nuclear pore complex (NPC) is a large macromolecular assembly of around 30 different proteins, so-called nucleoporins (Nups). Embedded in the nuclear envelope the NPC mediates bi-directional exchange between the cytoplasm and the nucleus and plays a role in transcriptional regulation that is poorly understood. NPCs display modular arrangements with an overall structure that is generally conserved among many eukaryotic phyla. However, Nups of yeast or human origin show little primary sequence conservation with those from early-branching protozoans leaving those of the malaria parasite unrecognized. Here we have combined bioinformatic and genetic methods to identify and spatially characterize Nup components in the rodent infecting parasite Plasmodium berghei and identified orthologs from the human malaria parasite P. falciparum, as well as the related apicomplexan parasite Toxoplasma gondii. For the first time we show the localization of selected Nups throughout the P. berghei life cycle. Largely restricted to apicomplexans we identify an extended C-terminal poly-proline extension in SEC13 that is essential for parasite survival and provide high-resolution images of Plasmodium NPCs obtained by cryo electron tomography. Our data provide the basis for full characterization of NPCs in malaria parasites, early branching unicellular eukaryotes with significant impact on human health., The work was funded by the cluster of excellence CellNetworks at Heidelberg University, the European Research Council (ERC StG 281719), the Alexander von Humboldt foundation through a postdoctoral fellowships to ND. MK is supported by the Sofja Kovalevskaja Award from the Humboldt Foundation and acknowledges support from the Max Planck Society.

Im Rahmen dieser Arbeit wurde ein hochgenaues und robustes Sekundärradar-Tachymeter für den Einsatz unter widrigen Umgebungsbedingungen wie z.B. Regen, Nebel oder Staub konzipiert, realisiert und in verschiedenen Anwendungsszenarien erprobt. Das System aus zwei Radareinheiten wurde in einen Liebherr Mobilkran integriert und auf dem Gelände der Liebherr-Werke Ehingen während einer einwöchigen Messkampagne erfolgreich bei verschiedenen Baueinsätzen getestet. Dabei wurde die Kranausladung während des Betriebes erstmalig mit einem RMSE von 15 cm in Echtzeit bestimmt. Die darauf basierte Lastmomentberechnung stellt besondere Anforderungen an die funktionale Sicherheit, welche nach Kenntnis des Autors bisher von keinem anderen kabellosen Nahortungssystem erreicht wurden. Aufgrund der Kombination aus Abstands- und Winkelmessung ist mit dem erforschten Tachymeter eine direkte Lokalisierung bewegter Einheiten mithilfe einer einzelnen Mastereinheit möglich, womit eine deutliche Verringerung des Infrastrukturaufwandes im Vergleich zu anderen lediglich auf Abstandsmessungen basierten Nahortungssystemen einher geht. Mögliche weitere Anwendungen des Systems sind dabei vielseitig und erstrecken sich über den gesamten Bereich der industriellen Automation, Sicherungs- und Verkehrstechnik. Das entwickelte Radarsystem arbeitet im ISM-Band bei 24–24.25 GHz. Es beinhaltet 8 Empfangskanäle und einen Sendekanal. Die FMCW-Signalerzeugung wurde mithilfe eines 12GHz-VCO in einer Phasenregelschleife durchgeführt, mit anschließendem Frequenzverdoppler, bzw. mit subharmonischen Mischern in den Empfangspfaden. Der im Rahmen des Forschungsprojektes aufgebaute Digitalteil führt die A/D-Wandlung sowie die schnelle Fouriertransformation der Empfangssignale durch und berechnet das Ergebnis der Abstands- und Winkelmessung. Dabei wird eine Messwiederholrate von 25 Hz erreicht. Zur Abstandsmessung wird ein FMCW-Sekundärradaransatz verwendet, welcher die hochgenaue Synchronisation zweier Einheiten im RTOF-Verfahren erlaubt und dabei u.a. auch die Relativgeschwindigkeit der Einheiten ausgibt. Zur Bestimmung der Einfallswinkel von Signalen wurden verschiedene DOA-Algorithmen auf ihre Eignung im angestrebten Anwendungsfall untersucht. Als wesentliche Kriterien wurden dabei die Auflösung, die erreichbare Genauigkeit und Robustheit gegen Mehrwegesignale bei gegebenem SNR sowie der benötigte Rechenaufwand betrachtet. Aufgrund seiner niedrigen Komplexität und der erreichten hohen Robustheit wurde der Bartlett-Beamformer für kostengünstige Systeme mit niedrigem SNR ausgewählt. Für Umgebungen mit extremen Mehrwegen konnte bei höherem SNR dagegen eine deutliche Verbesserung der Auflösung mithilfe einer Kombination aus Bartlett-Beamformer und MUSIK-Algorithmus mit Array-Interpolation und Spatial Smoothing erreicht werden. Zur Realisierung der Radar-Winkelschätzung wurden Methoden zum Finden optimaler linearer Antennenarrays mit charakteristischen Eigenschaften erforscht, wie der Winkel-Eindeutigkeitsbereich, die Hauptkeulenbreite und das Nebenkeulenniveau. Dabei wurden die entsprechenden erreichbaren Werte in Abhängigkeit von der Antennenanzahl anhand bekannter optimaler Gitteranordnungen für bestimmte Hauptkeulenbreiten ermittelt. Zusätzlich wurden allgemeine freie Anordnungen untersucht, die weitere bisher nicht erreichte optimale Kombinationen aus Keulenbreite und Nebenkeulenniveau ermöglichen. Auf dieser Basis wurde ein 8-elementiges Array für den Einsatz am Mobilkran ausgewählt. Zur Suche weiterer Arrays mit 3 bis ca. 16 Antennen wurde ein entsprechender effizienter Algorithmus entwickelt. Das gefundene optimale Array wurde aus eigens realisierten Patchantennen aufgebaut. Zur Abdeckung des spezifizierten Winkelbereichs besteht jede Einzelantenne dabei aus einer Anordnung aus 8 Patch-Elementen, wodurch für die Einzelantenne ein Gewinn von 12.5 dBi bei 24 GHz mit einer 10dB-Keulenbreite in Azimut von ±10°, sowie einer 3dB-Breite von etwa ±35° in Elevation erreicht wurde. Das Radartachymeter wurde zunächst in der Absorberkammer des LHFT kalibriert. Dabei wurde eine Winkelmessgenauigkeit von 0.1° bei 95% Konfidenz sowie ein RMSE von 0.05° erreicht. Der Winkelmessbereich beträgt ±35° in Elevation. Auf einem stillgelegten Flugplatz wurden Messungen mit einer Reichweite von bis zu 270 m durchgeführt. Für Abstände zwischen 2 und 220 m ergab sich eine Abstands-Messgenauigkeit von 4.6 cm und eine Winkel-Messgenauigkeit von 0.11° bei 95% Konfidenz, trotz starker Reflexion an der Fahrbahn. Zur Untersuchung der erreichbaren Winkelauflösung wurden zudem Messungen mit besonders starker Bodenreflexion durchgeführt. Bei einer Höhe der Einheiten über dem Boden von 60 cm wurde das Slave-Radar dazu vom Master weggefahren, hin zu Abständen zwischen 2 und 30 m. Anhand einer Kombination aus Bartlett-Beamformer und MUSIC-Algorithmus konnte das LOS-Signal bis hin zu einem kleinsten Winkelabstand von 2° eindeutig von der Bodenreflexion getrennt werden, wodurch die 5°-Auflösung des Bartlett-Beamformers deutlich übertroffen wurde. Dies stellt nach Kenntnis des Autors das bisher beste Ergebnis für vergleichbare Arrays bei entsprechendem SNR dar. Zur Erprobung des Systems in der Anwendung wurden die beiden Radareinheiten schließlich in einen Liebherr Mobilkran LTM1350-6.1 integriert. Während des Baueinsatzes wurde dabei ein RMSE von 2.2 cm im Abstand und 0.17° im Winkel erreicht, bei Abständen zwischen 1 und 60 m. Damit konnte erstmalig die Ausladung eines Kranes mit einer Genauigkeit von 32 cm bei 95% Konfidenz sowie mit einem RMSE von 15 cm bestimmt werden. Dies stellt eine deutliche Verbesserung im Vergleich zum Ergebnis herkömmlicher Systeme zur Ausladungsmessung dar und eröffnet neue Möglichkeiten beim Heben schwerer Lasten in anspruchsvollen Anwendungen. In this thesis, a highly accurate and robust secondary radar tachymeter for applications under adverse environmental conditions such as rain, fog or dust has been designed, implemented and tested in various field scenarios. The system consists of two radar units. It was mounted on a Liebherr mobile crane and tested during various construction operations on the proving ground of the Liebherr factory in Ehingen, Germany. Within this extensive test, it was shown that the working radius of the crane can be measured in real-time with a root-mean-square error (RMSE) of 15 cm during operation. The working radius has to be known in order to calculate the load torque on the crane, which allows the maximum load in the current boom position to be determined. To the knowledge of the author, the high level of functional safety required by the load measurement has not been achieved by other wireless localization systems. In this work, direct localization of moving targets is achieved with only one single master radar unit, due to the combined measurement of distance and angle. This significantly reduces the cost compared to other systems which are based only on distance measurement and therefore need multiple stationary units. Apart from the presented implementation on a mobile crane, there are also many other possible applications of the realized system in the sectors of industrial automation, security and traffic technology. The presented secondary radar works in the industrial, scientific and medical (ISM) band at 24–24.25 GHz. Each radar unit includes 8 receivers and one transmitter. The FMCW signal is generated by a 12 GHz voltage-controlled oscillator inside a phase-locked loop by using frequency doublers in the transmit path and subharmonic mixers in the receive paths. The unit’s digital part was designed within the research project RFTACH of the Bavarian Research Foundation. It performs the A/D conversion and fast Fourier transform of the received signals and calculates the corresponding angle and distance for each measurement. The system achieves a measurement rate of 25 Hz. The distance measurement is performed using an FMCW secondary radar approach which allows a highly accurate synchronization of two units with the roundtrip-time-of-flight technique. The relative velocity of the units is also determined. To measure the direction of arrival (DOA) of the signals, different algorithms were examined with regard to their applicability to the relevant use case. The main criteria were the achievable resolution, accuracy, robustness against multipath signals at a given SNR and the corresponding computational cost. Due to its low complexity and high robustness, the Bartlett beamformer was selected for low cost systems with low SNR. In environments with strong multipath effects, the resolution could be significantly improved by using a combination of the Bartlett beamformer and the MUSIC algorithm with array interpolation and spatial smoothing. To allow DOA estimation, methods for optimizing linear arrays with several characteristic properties were investigated, including the achievable sidelobe level and angular ambiguities. Based on known optimal grid arrays, these properties were estimated for different numbers of antennas depending on the desired main lobe width. Furthermore, general arrays with free antenna positions were examined in order to achieve additional combinations of beamwidth and sidelobe level that cannot be reached by grid arrays. An efficient algorithm was developed for arrays with 3 to approximately 16 elements. Using this algorithm, an 8-element array was chosen to be used at the mobile crane. The array was built with specially designed patch antennas, each consisting of 8 patch elements, to achieve a narrow beamwidth in azimuth. One antenna achieves a gain of 12.5 dBi at 24 GHz with a 10dB beamwidth of ±10° in azimuth to avoid disturbances from unwanted directions. The 3dB beamwidth of ±35° in elevation corresponds to the angular measurement range. Initially, the radar tachymeter was calibrated in the anechoic chamber at the Institute of Microwaves and Photonics (LHFT) in Erlangen. Here, an angular accuracy of 0.1° at a 95% confidence level was achieved, as well as an RMSE of 0.05°. At an unused landing strip, measurements with ranges of up to 270 m were performed. For ranges between 2 and 220 m, a distance accuracy of 4.6 cm and an angular accuracy of 0.11° at a 95% confidence level were achieved, despite strong ground reflections. To investigate the achievable angular resolution, measurements with extreme ground reflection were performed, with both units placed 60 cm from the ground. The slave radar was moved away from the master unit from 2 m up to a distance of 30 m. By using a combination of Bartlett beamformer and MUSIC algorithm, the line-of-sight signal could be clearly distinguished from the ground reflection up to a maximum resolution of 2°. Using only the Bartlett beamformer, a resolution of 5° could be achieved. To the knowledge of the author, this represents the best result for arrays of this size at the given SNR. The field test of the radar tachymeter was performed at the Liebherr site in Ehingen. Both radar units were mounted on a mobile crane LTM1350-6.1. During a building campaign, a distance RMSE of 2.2 cm and an angular RMSE of 0.17° in elevation were achieved for distances between 1 and 60 m. The working radius of the crane was determined with an accuracy of 32 cm at a 95% confidence level and an RMSE of 15 cm. This represents a significant improvement compared to existing solutions for determining the working radius and opens up new opportunities for the lifting of heavy loads in demanding applications.

OBJECTIVES The main objective of this study was to investigate the relationship among the in vivo acquisition of antimicrobial resistance in Pseudomonas aeruginosa clinical isolates, the underlying molecular mechanisms and previous exposure to antipseudomonal agents. METHODS PFGE was used to study the molecular relatedness of the strains. The MICs of ceftazidime, cefepime, piperacillin/tazobactam, imipenem, meropenem, ciprofloxacin and amikacin were determined. Outer membrane protein profiles were assessed to study OprD expression. RT-PCR was performed to analyse ampC, mexB, mexD, mexF and mexY expression. The presence of mutations was analysed through DNA sequencing. RESULTS We collected 17 clonally related paired isolates [including first positive samples (A) and those with MICs increased ≥4-fold (B)]. Most B isolates with increased MICs of imipenem, meropenem and ceftazidime became resistant to these drugs. The most prevalent resistance mechanisms detected were OprD loss (65%), mexB overexpression (53%), ampC derepression (29%), quinolone target gene mutations (24%) and increased mexY expression (24%). Five (29%) B isolates developed multidrug resistance. Meropenem was the most frequently (71%) received treatment, explaining the high prevalence of oprD mutations and likely mexB overexpression. Previous exposure to ceftazidime showed a higher impact on selection of increased MICs than previous exposure to piperacillin/tazobactam. CONCLUSIONS Stepwise acquisition of resistance has a critical impact on the resistance phenotypes of P. aeruginosa, leading to a complex scenario for finding effective antimicrobial regimens. In the clinical setting, meropenem seems to be the most frequent driver of multidrug resistance development, while piperacillin/tazobactam, in contrast to ceftazidime, seems to be the β-lactam least associated with the selection of resistance mechanisms.

Grapevine fanleaf virus (GFLV) is a nepovirus that is transmitted to grapevines by the ectoparasitic nematode Xiphinema index. GFLV causes severe losses in yield and quality in viticulture worldwide. Presently, laborious and time-consuming field trials or greenhouse tests are necessary for screening putative GFLV resistance in new grape genotypes developed in breeding programmes. We developed an in vitro dual culture system for grapevines and nematode vectors that requires less time and space than inoculation experiments done in the greenhouse. Virus infection of in vitro grapevines was investigated using immunocapture-reverse transcriptase-polymerase chain reaction (IC-RT-PCR) analysis. The development of root galls induced by feeding nematodes on in vitro grapevines was also analysed. Virus infection in grapevines in the dual culture with viruliferous nematodes was detected six weeks post-inoculation. Root galls were always absent from parasitised in vitro grapevines with detectable virus infection, whereas they developed on some parasitised, but virus-negative tested grapevines. Therefore, root galls cannot be used as a reliable indicator for parasitism and virus transmission.

The caudal migration of facial branchiomotor (FBM) neurons from rhombomere (r) 4 to r6 in the hindbrain is an excellent model to study neuronal migration mechanisms. Although several Wnt/Planar Cell Polarity (PCP) components are required for FBM neuron migration, only Celsr1, an atypical cadherin, regulates the direction of migration in mice. In Celsr1 mutants, a subset of FBM neurons migrates rostrally instead of caudally. Interestingly, Celsr1 is not expressed in the migrating FBM neurons, but rather in the adjacent floor plate and adjoining ventricular zone. To evaluate the contribution of different expression domains to neuronal migration, we conditionally inactivated Celsr1 in specific cell types. Intriguingly, inactivation of Celsr1 in the ventricular zone of r3-r5, but not in the floor plate, leads to rostral migration of FBM neurons, greatly resembling the migration defect of Celsr1 mutants. Dye fill experiments indicate that the rostrally-migrated FBM neurons in Celsr1 mutants originate from the anterior margin of r4. These data suggest strongly that Celsr1 ensures that FBM neurons migrate caudally by suppressing molecular cues in the rostral hindbrain that can attract FBM neurons.

Selection on naturally occurring hybrid individuals is a key component of speciation theory, but few studies examine the functional basis of hybrid performance. We examine the functional consequences of hybridization in nature, using the freshwater sunfishes (Centrarchidae), where natural hybrids have been studied for more than a century and a half. We examined bluegill (Lepomis macrochirus), green sunfish (Lepomis cyanellus), and their naturally occurring hybrid, using prey-capture kinematics and morphology to parameterize suction-feeding simulations on divergent parental resources. Hybrid individuals exhibited kinematics intermediate between those of the two parental species. However, performance assays indicated that hybrids display performance most similar to the worse-performing species for a given parental resource. Our results show that intermediate hybrid phenotypes can be impaired by a less-than-intermediate performance and hence suffer a larger loss in fitness than could be inferred from morphology alone.

Atherosclerosis and aortic valve sclerosis are cardiovascular diseases with an increasing prevalence in western societies. Statins are widely applied in atherosclerosis therapy, whereas no pharmacological interventions are available for the treatment of aortic valve sclerosis. Therefore, valve replacement surgery to prevent acute heart failure is the only option for patients with severe aortic stenosis. Both atherosclerosis and aortic valve sclerosis are not simply the consequence of degenerative processes, but rather diseases driven by inflammatory processes in response to lipid-deposition in the blood vessel wall and the aortic valve, respectively. The p38 mitogen-activated protein kinase (MAPK) is involved in inflammatory signaling and activated in response to various intracellular and extracellular stimuli, including oxidative stress, cytokines, and growth factors, all of which are abundantly present in atherosclerotic and aortic valve sclerotic lesions. The responses generated by p38 MAPK signaling in different cell types present in the lesions are diverse and might support the progression of the diseases. This review summarizes experimental findings relating to p38 MAPK in atherosclerosis and aortic valve sclerosis and discusses potential functions of p38 MAPK in the diseases with the aim of clarifying its eligibility as a pharmacological target.