Die @navigationsgestützte intraoperative Messung chirurgisch beeinflussbarer Faktoren und ihr Einfluss auf das klinische Ergebnis in der Knieendoprothetik

Zur Vorhersage der klinischen Ergebnisse in der Knieendoprothetik kommen sowohl patientenspezifische (PSF) als auch chirurgisch beeinflussbare Faktoren (SMF = surgically modifiable factors) in Betracht. Mithilfe eines Navigationssystems können zahlreiche dieser SMF präzise erfasst werden. Die Hypothese dieser Arbeit war: PSF und SMF können das klinische Ergebnis nach navigierter Knieprothesenimplantation vorhersagen. Es wurden die Daten von 99 Patienten (100 Knien) ausgewertet. Intraoperativ wurden mithilfe eines Navigationssystems 15 SMF gemessen. Präoperativ wurden PSF wie Größe, Gewicht, Alter und BMI dokumentiert. Bei den Nachuntersuchungen nach 3, 6, 12 Monaten und 4 Jahren wurden jeweils der Knee Society Score (KSS) und die Maximale Knieflexion (MKF) bestimmt. Mithilfe geeigneter statistischer Verfahren wurde überprüft, ob zwischen den unabhängigen Variablen (SMF, PSF) und den klinischen Daten (KSS, MKF) eine Beziehung bestand. Zur Vorhersage der MKF konnte ein Modell ermittelt werden, welches 32% der Variabilität erklärt (p=0,001). Zur Vorhersage des KSS-F konnte ein Modell ermittelt werden, welches 20% der Variabilität erklärt (p=0,007). Es konnte nachgewiesen werden, dass bestimmte SMF, welche die Weichteilbalance repräsentieren, sich zur Vorhersage von KSS und MKF eignen. In dieser Studie erwies sich das Navigationssystem als geeignetes präzises Messinstrument zur Ermittlung zahlreicher SMF. Die Hypothese, dass bestimmte PSF und SMF sich zur Vorhersage des klinischen Ergebnisses in der Knieendoprothetik eignen, konnte bestätigt werden. Mithilfe der Navigation könnten die chirurgisch beeinflussbaren Faktoren mit einem Einfluss auf das klinische Ergebnis in der Knieendoprothetik weiter evaluiert werden

Deciphering and modulating G protein signalling in C. elegans using the DREADD technology

G-protein signalling is an evolutionary conserved concept highlighting its fundamental impact on developmental and functional processes. Studies on the effects of G protein signals on tissues as well as an entire organism are often conducted in Caenorhabditis elegans. To understand and control dynamics and kinetics of the processes involved, pharmacological modulation of specific G protein pathways would be advantageous, but is difficult due to a lack in accessibility and regulation. To provide this option, we designed G protein-coupled receptor-based designer receptors (DREADDs) for C. elegans. Initially described in mammalian systems, these modified muscarinic acetylcholine receptors are activated by the inert drug clozapine N-oxide, but not by their endogenous agonists. We report a novel C. elegans-specific DREADD, functionally expressed and specifically activating Gq-protein signalling in vitro and in vivo which we used for modulating mating behaviour. Therefore, this novel designer receptor demonstrates the possibility to pharmacologically control physiological functions in C. elegans

Immunosuppressive M2 TAMs represent a promising target population to enhance phagocytosis of ovarian cancer cells in vitro

IntroductionTumor-associated macrophages (TAMs) represent an important cell population within the tumor microenvironment, but little is known about the phenotype and function of these cells. The present study aims to characterize macrophages in high-grade serous ovarian cancer (HGSOC).MethodsPhenotype and expression of co-regulatory markers were assessed on TAMs derived from malignant ascites (MA) or peripheral blood (PB) by multiparametric flow cytometry. Samples were obtained from HGSOC patients (n=29) and healthy donors (HDs, n=16). Additional expression analysis was performed by RNAseq (n=192). Correlation with clinically relevant parameters was conducted and validated by a second patient cohort (n=517). Finally, the role of TIGIT in repolarization and phagocytosis was investigated in vitro.ResultsExpression of the M2-associated receptors CD163, CD204, and CD206, as well as of the co-regulatory receptors TIGIT, CD226, TIM-3, and LAG-3 was significantly more frequent on macrophages in HGSOC than in HDs. CD39 and CD73 were broadly expressed on (mainly M2) macrophages, but without a clear clustering in HGSOC. CD163 mRNA levels were higher in TAMs from patients with residual tumor mass after surgery and associated with a shorter overall survival. In addition, TIGIT expression was associated with a higher tumor grading, indicating a prognostic relevance of M2 infiltration in HGSOC. TIGIT blockade significantly reduced the frequency of M2 macrophages. Moreover, combined blockade of TIGIT and CD47 significantly increased phagocytosis of ovarian cancer cells by TAMs in comparison to a single blockade of CD47.ConclusionCombined blockade of TIGIT and CD47 represents a promising approach to enhance anti-CD47-facilitated phagocytosis

Middepth circulation of the eastern tropical South Pacific and its link to the oxygen minimum zone

There is an incomplete description of the mid-depth circulation and its link to the oxygen minimum zone (OMZ) in the eastern tropical South Pacific. Subsurface currents of the OMZ in the eastern tropical South Pacific are investigated with a focus at 400 m depth, close to the core of the OMZ, using several Acoustic Doppler Current Profiler sections recorded in January and February 2009. Five profiling floats with oxygen sensors were deployed along 85°50’W in February 2009 with a drift depth at 400 m. Their spreading paths are compared with the model flow field from a 1/10° Tropical Pacific model (TROPAC01) and the Simple Ocean Data Assimilation (SODA) model. Overall the mean currents in the eastern tropical South Pacific are weak so that eddy variability influences the flow and ultimately feed oxygen-poor water to the OMZ. The center of the OMZ is a stagnant area so that floats stay much longer in this region and can even reverse direction. In one case of one float deployed at 8°S returned to the same location after 15 month. On the northern side of the OMZ in the equatorial current system, floats move rapidly to the west. Most current bands reported for the near surface layer exist also in the depth range of the OMZ. A schematic circulation flow field for the OMZ core depth is derived which shows the northern part of the South Pacific subtropical gyre south of the OMZ and the complicated zonal equatorial flow field north of the OMZ

Five Years of SMARTnet: Data, Processing, and Improvements

SMARTnet, operated by the Astronomical Institute of the University of Bern (AIUB) and the German Aerospace Center (DLR), went online and open to the public in 2017 with two telescope stations located in Zimmerwald, Switzerland, and Sutherland, South Africa. Over its five-year operational timespan, new partners have joined while one partner left, leaving telescope stations distributed today in Australia, South Africa, and Europe. All stations combined, 9 telescopes are actively providing data to the network. New contributors are currently in the applicant phase and will, together with further stations planned by DLR, enhance the network’s capabilities. The retrieved data is used for research, collision warnings, catalogue maintenance or for deriving data products, which can be sold to third parties. For the aforementioned points, the Backbone Catalogue of Relational Debris Information (BACARDI) was developed at DLR. BACARDI processes input data received from SMARTnet to data products such as ephemerides and orbit information for telescope observation planning, and attempts to detect new objects where an association of observations to already known objects is unsuccessful. To better operate the telescope stations, a dedicated software, called SMARTies, is under development in a joint project by AIUB and DLR. With this software, the telescope stations operations can be optimized to increase the daily data acquisition. It is planned to release SMARTies as Open Source software. To avoid deteriorating accuracy of the orbital information, ephemerides forecasted by BACARDI are combined with the planning tool “Optimal Catalog Maintenance and Survey Tasking” (OMST), which will help keeping all resident space objects in the data base. Furthermore, OMST will allow to search for new objects in the vicinity of the telescopes’ field of view in so-called “dead-times”. A short introduction to SMARTnet and its requirements is given, followed by some products retrieved from SMARTnet data. Also, the complete end-to-end chain from observations to processing, forecast, and its feed-back loop to observations is presented. Lastly, selected campaigns of some of the telescopes are presented. As part of non-regular observations, supporting observations can be acquired in case of special events (e.g. DART)

Climatic and edaphic controls over tropical forest diversity and vegetation carbon storage

Tropical rainforests harbor exceptionally high biodiversity and store large amounts of carbon in vegetation biomass. However, regional variation in plant species richness and vegetation carbon stock can be substantial, and may be related to the heterogeneity of topoedaphic properties. Therefore, aboveground vegetation carbon storage typically differs between geographic forest regions in association with the locally dominant plant functional group. A better understanding of the underlying factors controlling tropical forest diversity and vegetation carbon storage could be critical for predicting tropical carbon sink strength in response to projected climate change. Based on regionally replicated 1-ha forest inventory plots established in a region of high geomorphological heterogeneity we investigated how climatic and edaphic factors affect tropical forest diversity and vegetation carbon storage. Plant species richness (of all living stems >10 cm in diameter) ranged from 69 to 127 ha-1 and vegetation carbon storage ranged from 114 to 200 t ha-1. While plant species richness was controlled by climate and soil water availability, vegetation carbon storage was strongly related to wood density and soil phosphorus availability. Results suggest that local heterogeneity in resource availability and plant functional composition should be considered to improve projections of tropical forest ecosystem functioning under future scenarios

Titin-truncating variants affect heart function in disease cohorts and the general population

Titin-truncating variants (TTNtv) commonly cause dilated cardiomyopathy (DCM). TTNtv are also encountered in ~1% of the general population, where they may be silent, perhaps reflecting allelic factors. To better understand TTNtv, we integrated TTN allelic series, cardiac imaging and genomic data in humans and studied rat models with disparate TTNtv. In patients with DCM, TTNtv throughout titin were significantly associated with DCM. Ribosomal profiling in rat showed the translational footprint of premature stop codons in Ttn, TTNtv-position-independent nonsense-mediated degradation of the mutant allele and a signature of perturbed cardiac metabolism. Heart physiology in rats with TTNtv was unremarkable at baseline but became impaired during cardiac stress. In healthy humans, machine-learning-based analysis of high-resolution cardiac imaging showed TTNtv to be associated with eccentric cardiac remodeling. These data show that TTNtv have molecular and physiological effects on the heart across species, with a continuum of expressivity in health and disease

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements