Identification of the Molecular Mechanism in Scar Regeneration by Studying the Cellular Crosstalk between Adipocytes and Connective Tissue

Abnormal scarring and its accompanying cosmetic, functional and psychological burden is a major challenge in modern medicine. Pathological scars such as hypertrophic scars or keloids present cutaneous conditions characterized by excessive collagen deposition which can be itchy and painful, causing serious functional and aesthetical disabilities. The crucial role of myofibroblasts and transforming growth factor-beta (TGF-β) signaling in the pathogenesis of fibrosis and, thus, scarring, is widely accepted. Nevertheless, effective preventive or therapeutic strategies are still not available despite extensive research. Autologous fat grafting is a novel approach leading to partly significant improvements of scar tissue regarding functionality and appearance. Here, fat is harvested from body deposits and re-injected into areas with scarred tissue. Since adipose tissue does not only contain adipocytes but is a source for adipose-derived stem cells (ASCs) and even more cell types, various origins for the observed scar regeneration are conceivable. Regenerative effects from adipocytes or ASCs are discussed, however, the underlying mechanism is still unknown. Aiming to unravel the regenerative potential of adipose tissue, paracrine effects of ASCs and adipocytes on in vitro differentiated myofibroblasts and fibroblasts from hypertrophic scars were investigated. Interestingly, following incubation with adipocyteconditioned medium, the expression of the myofibroblast marker α-smooth muscle actin and the extracellular matrix components collagen 1 and 3 decreased significantly indicating a myofibroblast reprogramming. Secretome analysis, ELISA, Western blot and high throughput protein analysis indicate a pivotal role of BMP-4 secreted by adipocytes in the cellular reprogramming. In addition, direct as well as indirect activation of peroxisome proliferator-activated receptor (PPAR)γ signaling was shown after application of conditioned medium from adipocytes. Remarkably, speculations about a reciprocal, antagonistic relationship between PPARɣ and TGF-β do exist which might indicate anti-fibrotic effects on the part of PPARɣ. Although a myofibroblast-to-adipocyte transition was hypothesised, myofibroblasts trans-differentiation, however, was not observed. Overall, adipocytes induce myofibroblast reprogramming via BMP-4 secretion and by direct as well as indirect activation of PPARγ signaling. These findings highlight the regenerative potential of adipocytes on scar tissue and may pave the way for novel therapeutic strategies in the prevention or treatment of hypertrophic scars

Performance Analysis of Bearings-only Tracking Problems for Maneuvering Target and Heterogeneous Sensor Applications

State estimation, i.e. determining the trajectory, of a maneuvering target from noisy measurements collected by a single or multiple passive sensors (e.g. passive sonar and radar) has wide civil and military applications, for example underwater surveillance, air defence, wireless communications, and self-protection of military vehicles. These passive sensors are listening to target emitted signals without emitting signals themselves which give them concealing properties. Tactical scenarios exists where the own position shall not be revealed, e.g. for tracking submarines with passive sonar or tracking an aerial target by means of electro-optic image sensors like infrared sensors. This estimation process is widely known as bearings-only tracking. On the one hand, a challenge is the high degree of nonlinearity in the estimation process caused by the nonlinear relation of angular measurements to the Cartesian state. On the other hand, passive sensors cannot provide direct target location measurements, so bearings-only tracking suffers from poor target trajectory estimation accuracy due to marginal observability from sensor measurements. In order to achieve observability, that means to be able to estimate the complete target state, multiple passive sensor measurements must be fused. The measurements can be recorded spatially distributed by multiple dislocated sensor platforms or temporally distributed by a single, moving sensor platform. Furthermore, an extended case of bearings-only tracking is given if heterogeneous measurements from targets emitting different types of signals, are involved. With this, observability can also be achieved on a single, not necessarily moving platform. In this work, a performance bound for complex motion models, i.e. piecewisely maneuvering targets with unknown maneuver change times, by means of bearings-only measurements from a single, moving sensor platform is derived and an efficient estimator is implemented and analyzed. Furthermore, an observability analysis is carried out for targets emitting acoustic and electromagnetic signals. Here, the different signal propagation velocities can be exploited to ensure observability on a single, not necessarily moving platform. Based on the theoretical performance and observability analyses a distributed fusion system has been realized by means of heterogeneous sensors, which shall detect an event and localize a threat. This is performed by a microphone array to detect sound waves emitted by the threat as well as a radar detector that detects electromagnetic emissions from the threat. Since multiple platforms are involved to provide increased observability and also redundancy against possible breakdowns, a WiFi mobile ad hoc network is used for communications. In order to keep up the network in a breakdown OLSR (optimized link state routing) routing approach is employed

A Search for Magnesium in Europa's Atmosphere

Europa's tenuous atmosphere results from sputtering of the surface. The trace element composition of its atmosphere is therefore related to the composition of Europa's surface. Magnesium salts are often invoked to explain Galileo Near Infrared Mapping Spectrometer spectra of Europa's surface, thus magnesium may be present in Europa's atmosphere. We have searched for magnesium emission in the Hubble Space Telescope Faint Object Spectrograph archival spectra of Europa's atmosphere. Magnesium was not detected and we calculate an upper limit on the magnesium column abundance. This upper limit indicates that either Europa's surface is depleted in magnesium relative to sodium and potassium, or magnesium is not sputtered as efficiently resulting in a relative depletion in its atmosphere

Limits on Clouds and Hazes for the TRAPPIST-1 Planets

The TRAPPIST-1 planetary system is an excellent candidate for study of the evolution and habitability of M-dwarf planets. Transmission spectroscopy observations performed with the Hubble Space Telescope (HST) suggest the innermost five planets do not possess clear hydrogen atmospheres. Here we reassess these conclusions with recently updated mass constraints and expand the analysis to include limits on metallicity, cloud top pressure, and the strength of haze scattering. We connect recent laboratory results of particle size and production rate for exoplanet hazes to a one-dimensional atmospheric model for TRAPPIST-1 transmission spectra. Doing so, we obtain a physically-based estimate of haze scattering cross sections. We find haze scattering cross sections on the order of 1e-26 to 1e-19 cm squared are needed in hydrogen-rich atmospheres for TRAPPIST-1 d, e, and f to match the HST data. For TRAPPIST-1 g, we cannot rule out a clear hydrogen-rich atmosphere. We also modeled the effects an opaque cloud deck and substantial heavy element content have on the transmission spectra. We determine that hydrogen-rich atmospheres with high altitude clouds, at pressures of 12mbar and lower, are consistent with the HST observations for TRAPPIST-1 d and e. For TRAPPIST-1 f and g, we cannot rule out clear hydrogen-rich cases to high confidence. We demonstrate that metallicities of at least 60xsolar with tropospheric (0.1 bar) clouds agree with observations. Additionally, we provide estimates of the precision necessary for future observations to disentangle degeneracies in cloud top pressure and metallicity. Our results suggest secondary, volatile-rich atmospheres for the outer TRAPPIST-1 planets d, e, and f.Comment: 15 pages, 3 figures, 2 tables, accepted in the Astronomical Journa

Exploring the Atmosphere of Neoproterozoic Earth: The Effect of O2_{2} on Haze Formation and Composition

Previous studies of haze formation in the atmosphere of the Early Earth have focused on N$_{2}$/CO$_{2}$/CH$_{4}$ atmospheres. Here, we experimentally investigate the effect of O$_{2}$ on the formation and composition of aerosols to improve our understanding of haze formation on the Neoproterozoic Earth. We obtained in situ size, particle density, and composition measurements of aerosol particles produced from N$_{2}$/CO$_{2}$/CH$_{4}$/O$_{2}$ gas mixtures subjected to FUV radiation (115-400 nm) for a range of initial CO$_{2}$/CH$_{4}$/O$_{2}$ mixing ratios (O$_{2}$ ranging from 2 ppm to 0.2\%). At the lowest O$_{2}$ concentration (2 ppm), the addition increased particle production for all but one gas mixture. At higher oxygen concentrations (20 ppm and greater) particles are still produced, but the addition of O$_{2}$ decreases the production rate. Both the particle size and number density decrease with increasing O$_{2}$, indicating that O$_{2}$ affects particle nucleation and growth. The particle density increases with increasing O$_{2}$. The addition of CO$_{2}$ and O$_{2}$ not only increases the amount of oxygen in the aerosol, but it also increases the degree of nitrogen incorporation. In particular, the addition of O$_{2}$ results in the formation of nitrate bearing molecules. The fact that the presence of oxygen bearing molecules increases the efficiency of nitrogen fixation has implications for the role of haze as a source of molecules required for the origin and evolution of life. The composition changes also likely affect the absorption and scattering behavior of these particles but optical properties measurements are required to fully understand the implications for the effect on the planetary radiative energy balance and climate.Comment: 15 pages, 3 tables, 8 figures, accepted in Astrophysical Journa

Exploring the atmosphere of Neoproterozoic Earth: The effect of O2 on haze formation and composition

Previous studies of haze formation in the atmosphere of the early Earth have focused on N2/CO2/CH4 atmospheres. Here, we experimentally investigate the effect of O2 on the formation and composition of aerosols to improve our understanding of haze formation on the Neoproterozoic Earth. We obtained in situ size, particle density, and composition measurements of aerosol particles produced from N2/CO2/CH4/O2 gas mixtures subjected to FUV radiation (115–400 nm) for a range of initial CO2/CH4/O2 mixing ratios (O2 ranging from 2 ppm to 0.2%). At the lowest O2 concentration (2 ppm), the addition increased particle production for all but one gas mixture. At higher oxygen concentrations (20 ppm and greater), particles are still produced, but the addition of O2 decreases the production rate. Both the particle size and number density decrease with increasing O2, indicating that O2 affects particle nucleation and growth. The particle density increases with increasing O2. The addition of CO2 and O2 not only increases the amount of oxygen in the aerosol, but it also increases the degree of nitrogen incorporation. In particular, the addition of O2 results in the formation of nitrate-bearing molecules. The fact that the presence of oxygen-bearing molecules increases the efficiency of nitrogen fixation has implications for the role of haze as a source of molecules required for the origin and evolution of life. The composition changes also likely affect the absorption and scattering behavior of these particles but optical property measurements are required to fully understand the implications for the effect on the planetary radiative energy balance and climate