Orientierte Magnetfeldmessungen während IODP Expedition 330 zur Louisville Seamount Chain

The major objective of this thesis is to reorient and analyze three component magnetic field data recorded in two boreholes during Integrated Ocean Drilling Program (IODP) Expedition 330 to the Louisville Seamount Chain. One aim of the expedition was to determine whether the hotspot that created the seamount chain during the past 80 million years is moving relative to the Hawaiian-Emperor hotspot or if it remained stationary within the mantle. The magnetic field measurements were conducted with the Göttinger Bohrlochmagnetometer, which comprises fibre optic gyros that measure the rotations of the tool within the borehole. In this thesis, I use different algorithms to reorient the measured magnetic field from the tools reference frame into the geographical reference frame. This purpose requires sensors of high accuracy and careful data processing. I present several reorientation algorithms; among others, I introduce two new sensor fusion algorithms for gyro and inclinometer data based on a Kalman filter. Oriented magnetic field data can be used to determine both the inclination and declination of the magnetization of the rocks surrounding the borehole by the application of appropriate models. Measurements on drill core samples can typically only be used to determine the inclination of magnetization, as cores are usually azimuthally unoriented. In the subsequent analysis of the oriented magnetic field data, I use different models for the drilled igneous layers to calculate the magnetization of the subsurface. As horizontal layers turn out to be insufficient to explain the data, I extend the interpretation to inclined layers. I introduce a new approximation for the magnetic field of inclined layers that can be used to separate the calculation of magnetization in an inversion using horizontal layers and a following consideration of potential layer geometries. My approximation additionally reveals possible ambiguities and errors of the measurements. Using images of the borehole wall that give additional information about the possible geometry of a drilled layer inside Burton Guyot (Site U1376), I determine a mean inclination of magnetization of 58.9° and a mean declination of magnetization of 0.4°. These results agree with current theories of a stationary Louisville hotspot. In addition, the result for the declination suggests that Burton Guyot has not been rotated since its formation.Das Thema dieser Doktorarbeit ist die Reorientierung und Auswertung von vektoriellen Magnetfelddaten, die in zwei Bohrungen während der IODP Expedition 330 zu den Louisville Seamounts aufgezeichnet wurden. Ein Ziel der Expedition war festzustellen, ob der Hotspot, der für die Entstehung dieser Inselkette im Laufe der vergangenen 80 Millionen Jahre verantwortlich ist, sich relativ zu dem Hawaiian-Emperor Hotspot bewegte oder ob er stationär blieb. Für die Magnetfeldmessungen wurde das Göttinger Bohrlochmagnetometer verwendet, dessen faseroptische Kreisel in der Lage sind, die Drehungen der Sonde im Bohrloch zu bestimmen, wodurch das gemessene Magnetfeld aus dem Bezugssystem der Sonde in das geographische Koordinatensystem reorientiert werden kann. Hierfür ist eine hochgenaue Sensorik und sorgfältige Datenprozessierung nötig. Ich stelle verschiedene Reorientierungsalgorithmen vor, unter anderem zwei neue Sensorfusionsalgorithmen für Faserkreisel- und Inklinometerdaten die auf einem Kalman Filter basieren. Der Vorteil von orientierten Magnetfeldmessungen ist, dass man über entsprechende Modelle neben der Inklination auch die Deklination der Magnetisierung des die Bohrung umgebenden Gesteins bestimmen kann. Anhand von Messungen an Bohrkernen lässt sich häufig nur die Inklination der Magnetisierung bestimmen, da die Kerne meist unorientiert entnommen werden. Für die Auswertung der Magnetfelddaten verwende ich verschiedene Modelle. Da horizontale Schichtmodelle nicht ausreichen um die vorhandenen Daten zu erklären, weite ich die Interpretation auf geneigte Schichten aus. Hierzu stelle ich eine neue Näherung vor, die es ermöglicht, die Inversion der Magnetisierung in zwei Schritte aufzuteilen. Zuerst wird ein Horizontalschichtmodell berechnet, woraufhin getrennt davon im zweiten Schritt mögliche Schichtgeometrien berücksichtigt werden. Die Näherung kann auch dafür benutzt werden, um Aussagen über mögliche Uneindeutigkeiten von Messungen zu treffen. Unter Zuhilfenahme von Informationen über mögliche Schichtgeometrien aus Bildern der Bohrlochwand ermittle ich aus Daten einer Schicht des Burton Guyot (Site U1376) eine mittlere Inklination und Deklination der Magnetisierung von 58.9° und 0.4°. Diese Ergebnisse stimmen mit gängigen Theorien überein, die von einem stationären Louisville-Hotspot ausgehen. Die Ergebnisse für die Deklination deuten darauf hin, dass Burton Guyot seit seiner Entstehung nicht gedreht wurde

Melody Transcription From Music Audio: Approaches and Evaluation

Although the process of analyzing an audio recording of a music performance is complex and difficult even for a human listener, there are limited forms of information that may be tractably extracted and yet still enable interesting applications. We discuss melody--roughly, the part a listener might whistle or hum--as one such reduced descriptor of music audio, and consider how to define it, and what use it might be. We go on to describe the results of full-scale evaluations of melody transcription systems conducted in 2004 and 2005, including an overview of the systems submitted, details of how the evaluations were conducted, and a discussion of the results. For our definition of melody, current systems can achieve around 70% correct transcription at the frame level, including distinguishing between the presence or absence of the melody. Melodies transcribed at this level are readily recognizable, and show promise for practical applications

Synthetic Light-Activated Ion Channels for Optogenetic Activation and Inhibition

Optogenetic manipulation of cells or living organisms became widely used in neuroscience following the introduction of the light-gated ion channel channelrhodopsin-2 (ChR2). ChR2 is a non-selective cation channel, ideally suited to depolarize and evoke action potentials in neurons. However, its calcium (Ca2+) permeability and single channel conductance are low and for some applications longer-lasting increases in intracellular Ca2+ might be desirable. Moreover, there is need for an efficient light-gated potassium (K+) channel that can rapidly inhibit spiking in targeted neurons. Considering the importance of Ca2+ and K+ in cell physiology, light-activated Ca2+-permeant and K+-specific channels would be welcome additions to the optogenetic toolbox. Here we describe the engineering of novel light-gated Ca2+-permeant and K+-specific channels by fusing a bacterial photoactivated adenylyl cyclase to cyclic nucleotide-gated channels with high permeability for Ca2+ or for K+, respectively. Optimized fusion constructs showed strong light-gated conductance in Xenopus laevis oocytes and in rat hippocampal neurons. These constructs could also be used to control the motility of Drosophila melanogaster larvae, when expressed in motoneurons. Illumination led to body contraction when motoneurons expressed the light-sensitive Ca2+-permeant channel, and to body extension when expressing the light-sensitive K+ channel, both effectively and reversibly paralyzing the larvae. Further optimization of these constructs will be required for application in adult flies since both constructs led to eclosion failure when expressed in motoneurons

Synthetic light-activated ion channels for optogenetic activation and inhibition

Optogenetic manipulation of cells or living organisms became widely used in neuroscience following the introduction of the light-gated ion channel channelrhodopsin-2 (ChR2). ChR2 is a non-selective cation channel, ideally suited to depolarize and evoke action potentials in neurons. However, its calcium (Ca2$^{2+}$) permeability and single channel conductance are low and for some applications longer-lasting increases in intracellular Ca$^{2+}$ might be desirable. Moreover, there is need for an efficient light-gated potassium (K$^{+}$) channel that can rapidly inhibit spiking in targeted neurons. Considering the importance of Ca$^{2+}$ and K$^{+}$ in cell physiology, light-activated Ca$^{2+}$-permeant and K$^{+}$-specific channels would be welcome additions to the optogenetic toolbox. Here we describe the engineering of novel light-gated Ca$^{2+}$-permeant and K$^{+}$-specific channels by fusing a bacterial photoactivated adenylyl cyclase to cyclic nucleotide-gated channels with high permeability for Ca$^{2+}$ or for K$^{+}$, respectively. Optimized fusion constructs showed strong light-gated conductance in Xenopus laevis oocytes and in rat hippocampal neurons. These constructs could also be used to control the motility of Drosophila melanogaster larvae, when expressed in motoneurons. Illumination led to body contraction when motoneurons expressed the light-sensitive Ca$^{2+}$-permeant channel, and to body extension when expressing the light-sensitive K$^{+}$ channel, both effectively and reversibly paralyzing the larvae. Further optimization of these constructs will be required for application in adult flies since both constructs led to eclosion failure when expressed in motoneurons

Association of Interprofessional Discharge Planning Using an Electronic Health Record Tool With Hospital Length of Stay Among Patients with Multimorbidity: A Nonrandomized Controlled Trial

Whether interprofessional collaboration is effective and safe in decreasing hospital length of stay remains controversial.; To evaluate the outcomes and safety associated with an electronic interprofessional-led discharge planning tool vs standard discharge planning to safely reduce length of stay among medical inpatients with multimorbidity.; This multicenter prospective nonrandomized controlled trial used interrupted time series analysis to examine medical acute hospitalizations at 82 hospitals in Switzerland. It was conducted from February 2017 through January 2019. Data analysis was conducted from March 2021 to July 2022.; After a 12-month preintervention phase (February 2017 through January 2018), an electronic interprofessional-led discharge planning tool was implemented in February 2018 in 7 intervention hospitals in addition to standard discharge planning.; Mixed-effects segmented regression analyses were used to compare monthly changes in trends of length of stay, hospital readmission, in-hospital mortality, and facility discharge after the implementation of the tool with changes in trends among control hospitals.; There were 54 695 hospitalizations at intervention hospitals, with 27 219 in the preintervention period (median [IQR] age, 72 [59-82] years; 14 400 [52.9%] men) and 27 476 in the intervention phase (median [IQR] age, 72 [59-82] years; 14 448 [52.6%] men) and 438 791 at control hospitals, with 216 261 in the preintervention period (median [IQR] age, 74 [60-83] years; 109 770 [50.8%] men) and 222 530 in the intervention phase (median [IQR] age, 74 [60-83] years; 113 053 [50.8%] men). The mean (SD) length of stay in the preintervention phase was 7.6 (7.1) days for intervention hospitals and 7.5 (7.4) days for control hospitals. During the preintervention phase, population-averaged length of stay decreased by -0.344 hr/mo (95% CI, -0.599 to -0.090 hr/mo) in control hospitals; however, no change in trend was observed among intervention hospitals (-0.034 hr/mo; 95% CI, -0.646 to 0.714 hr/mo; difference in slopes, P = .09). Over the intervention phase (February 2018 through January 2019), length of stay remained unchanged in control hospitals (slope, -0.011 hr/mo; 95% CI, -0.281 to 0.260 hr/mo; change in slope, P = .03), but decreased steadily among intervention hospitals by -0.879 hr/mo (95% CI, -1.607 to -0.150 hr/mo; change in slope, P = .04, difference in slopes, P = .03). Safety analyses showed no change in trends of hospital readmission, in-hospital mortality, or facility discharge over the whole study time.; In this nonrandomized controlled trial, the implementation of an electronic interprofessional-led discharge planning tool was associated with a decline in length of stay without an increase in hospital readmission, in-hospital mortality, or facility discharge.; isrctn.org Identifier: ISRCTN83274049

Quantitative super-resolution imaging of Bruchpilot distinguishes active zone states

The precise molecular architecture of synaptic active zones (AZs) gives rise to different structural and functional AZ states that fundamentally shape chemical neurotransmission. However, elucidating the nanoscopic protein arrangement at AZs is impeded by the diffraction-limited resolution of conventional light microscopy. Here we introduce new approaches to quantify endogenous protein organization at single-molecule resolution in situ with super-resolution imaging by direct stochastic optical reconstruction microscopy (dSTORM). Focusing on the Drosophila neuromuscular junction (NMJ), we find that the AZ cytomatrix (CAZ) is composed of units containing ~137 Bruchpilot (Brp) proteins, three quarters of which are organized into about 15 heptameric clusters. We test for a quantitative relationship between CAZ ultrastructure and neurotransmitter release properties by engaging Drosophila mutants and electrophysiology. Our results indicate that the precise nanoscopic organization of Brp distinguishes different physiological AZ states and link functional diversification to a heretofore unrecognized neuronal gradient of the CAZ ultrastructure

Immune evasion by proteolytic shedding of natural killer group 2, member D ligands in Helicobacter pylori infection

[Background]: Helicobacter pylori (H. pylori) uses various strategies that attenuate mucosal immunity to ensure its persistence in the stomach. We recently found evidence that H. pylori might modulate the natural killer group 2, member 2 (NKG2D) system. The NKG2D receptor and its ligands are a major activation system of natural killer and cytotoxic T cells, which are important for mucosal immunity and tumor immunosurveillance. The NKG2D system allows recognition and elimination of infected and transformed cells, however viruses and cancers often subvert its activation. Here we aimed to identify a potential evasion of the NKG2D system in H. pylori infection.[Methods]: We analyzed expression of NKG2D system genes in gastric tissues of H. pylori gastritis and gastric cancer patients, and performed cell-culture based infection experiments using H. pylori isogenic mutants and epithelial and NK cell lines.[Results]: In biopsies of H. pylori gastritis patients, NKG2D receptor expression was reduced while NKG2D ligands accumulated in the lamina propria, suggesting NKG2D evasion. In vitro, H. pylori induced the transcription and proteolytic shedding of NKG2D ligands in stomach epithelial cells, and these effects were associated with specific H. pylori virulence factors. The H. pylori-driven release of soluble NKG2D ligands reduced the immunogenic visibility of infected cells and attenuated the cytotoxic activity of effector immune cells, specifically the anti-tumor activity of NK cells.[Conclusion]: H. pylori manipulates the NKG2D system. This so far unrecognized strategy of immune evasion by H. pylori could potentially facilitate chronic bacterial persistence and might also promote stomach cancer development by allowing transformed cells to escape immune recognition and grow unimpeded to overt malignancy.Supported by the Austrian Science Fund (FWF, DK-MOLIN W1241 and the “Cluster of Excellence: Microbiomes Drive Planetary Health”) and by the Spanish Ministry of Science and Innovation under Grants (PID2021-123795OB-I00, PID2020-115506RB-I00) [Ministerio de Ciencia, Innovación y Universidades (MCIU)/Agencia Estatal de Investigación (AEI)/European Regional Development Fund (FEDER, EU)].Peer reviewe