Transforming Growth Factor Alpha Stimulation of Mucosal Tissue Cultures from Head and Neck Squamous Cell Carcinoma Patients Increases Chemoresistance to Cisplatin

The monoclonal epidermal growth factor receptor ( EGFR) antibody cetuximab (Erbitux(TM)) was recently approved by the European Medicines Agency for the treatment of recurrent and/or metastatic head and neck squamous cell carcinoma (HNSCC) in combination with a platinum-based chemotherapy. Since the antibody has only a limited effect as a monotherapy, possible explanations for the synergistic effect with cisplatin are enhanced antibody-dependent cytoxicity and increased sensitivity to the drug. Most of our knowledge of EGFR biology in HNSCC is based on studies using EGFR inhibitors and/or antibodies. Our study was designed to evaluate the impact of EGFR stimulation on cisplatin-induced DNA damage. Therefore, tissue cultures were produced of tumor-free oropharyngeal mucosa biopsies of HNSCC patients and controls. In a previous study, overexpression of EGFR in tissue cultures from tumor patients compared to controls was confirmed by immunohistochemical staining. Twenty-four-hour stimulation of tissue cultures with transforming growth factor alpha (TGF-alpha), a specific EGFR ligand, resulted in a reduction of cisplatin-induced DNA damage by 35% in cases, whereas in controls TGF-alpha had no effect. This reflects a statistically significant increase in cellular chemoresistance to cisplatin following TGF-alpha stimulation and helps to further understand effects of EGFR antisense therapy in combination with chemotherapy. Copyright (C) 2010 S. Karger AG, Base

ExoMDN: Rapid characterization of exoplanet interior structures with Mixture Density Networks

Characterizing the interior structure of exoplanets is essential for understanding their diversity, formation, and evolution. As the interior of exoplanets is inaccessible to observations, an inverse problem must be solved, where numerical structure models need to conform to observable parameters such as mass and radius. This is a highly degenerate problem whose solution often relies on computationally-expensive and time-consuming inference methods such as Markov Chain Monte Carlo. We present ExoMDN, a machine-learning model for the interior characterization of exoplanets based on Mixture Density Networks (MDN). The model is trained on a large dataset of more than 5.6 million synthetic planets below 25 Earth masses consisting of an iron core, a silicate mantle, a water and high-pressure ice layer, and a H/He atmosphere. We employ log-ratio transformations to convert the interior structure data into a form that the MDN can easily handle. Given mass, radius, and equilibrium temperature, we show that ExoMDN can deliver a full posterior distribution of mass fractions and thicknesses of each planetary layer in under a second on a standard Intel i5 CPU. Observational uncertainties can be easily accounted for through repeated predictions from within the uncertainties. We use ExoMDN to characterize the interior of 22 confirmed exoplanets with mass and radius uncertainties below 10% and 5% respectively, including the well studied GJ 1214 b, GJ 486 b, and the TRAPPIST-1 planets. We discuss the inclusion of the fluid Love number $k_2$ as an additional (potential) observable, showing how it can significantly reduce the degeneracy of interior structures. Utilizing the fast predictions of ExoMDN, we show that measuring $k_2$ with an accuracy of 10% can constrain the thickness of core and mantle of an Earth analog to $\approx13\%$ of the true values.Comment: 15 pages, 15 figures, accepted for publication in Astronomy & Astrophysics. The ExoMDN model is freely accessible at https://github.com/philippbaumeister/ExoMD

DNA-Fragmentierung in humanen Speicheldrüsenzellen und Lymphozyten nach Exposition gegenüber Metallsalzen und Ethanol

In vitro Testung von Schwermetallsalzen und Ethanol an humanen Speicheldrüsenzellen und Lymphozyten zur Evaluation des DNA-fragmentierenden Potenzials. Methode: Comet Assay

Redox state and interior structure control on the long-term habitability of stagnant-lid planets

A major goal in the search for extraterrestrial life is the detection of liquid water on the surface of exoplanets. On terrestrial planets, volcanic outgassing is a significant source of atmospheric and surface water and a major contributor to the long-term evolution of the atmosphere. The rate of volcanism depends on the interior evolution and on numerous feedback processes between atmosphere and interior, which continuously shape atmospheric composition, pressure, and temperature. We present the results of a comprehensive 1D model of the coupled evolution of the interior and atmosphere of rocky exoplanets that combines central feedback processes between these two reservoirs. We carried out more than \num{280000} simulations over a wide range of mantle redox states and volatile content, planetary masses, interior structures and orbital distances in order to robustly assess the emergence, accumulation and preservation of surface water on rocky planets. To establish a conservative baseline of which types of planets can outgas and sustain water on their surface, we focus here on stagnant-lid planets. We find that only a narrow range of the mantle redox state around the iron-w\"ustite buffer allows the formation of atmospheres that lead to long-term habitable conditions. At oxidizing conditions similar to those of the Earth's mantle, most stagnant-lid planets end up in a hothouse regime akin to Venus due to strong \ce{CO2} outgassing. At more reducing conditions, the amount of outgassed greenhouse gases is often too low to keep surface water from freezing. In addition, Mercury-like planets with large metallic cores are able to sustain habitable conditions at an extended range of orbital distances as a result of lower volcanic activity.Comment: 23 pages, 18 figures, accepted for publication in Astronomy & Astrophysic

Redox state and interior structure control on the long-term habitability of stagnant-lid planets

Context. A major goal in the search for extraterrestrial life is the detection of liquid water on the surface of exoplanets. On terrestrial planets, volcanic outgassing is a significant source of atmospheric and surface water and a major contributor to the long-term evolution of the atmosphere. The rate of volcanism depends on the interior evolution and on numerous feedback processes between the atmosphere and interior, which continuously shape atmospheric composition, pressure, and temperature. Aims. We explore how key planetary parameters, such as planet mass, interior structure, mantle water content, and redox state, shape the formation of atmospheres that permit liquid water on the surface of planets. Methods. We present the results of a comprehensive 1D model of the coupled evolution of the interior and atmosphere of rocky exoplanets that combines central feedback processes between these two reservoirs. We carried out more than 280 000 simulations over a wide range of mantle redox states and volatile content, planetary masses, interior structures, and orbital distances in order to robustly assess the emergence, accumulation, and preservation of surface water on rocky planets. To establish a conservative baseline of which types of planets can outgas and sustain water on their surface, we focus here on stagnant-lid planets. Results. We find that only a narrow range of the mantle redox state around the iron-wüstite buffer allows the formation of atmospheres that lead to long-term habitable conditions. At oxidizing conditions similar to those of the Earth's mantle, most stagnant-lid planets end up in a hothouse regime akin to Venus due to strong CO2 outgassing. At more reducing conditions, the amount of outgassed greenhouse gases is often too low to keep surface water from freezing. In addition, Mercury-like planets with large metallic cores are able to sustain habitable conditions at an extended range of orbital distances as a result of lower volcanic activity

Preoperative anemia and perioperative blood transfusion in head and neck squamous cell carcinoma

Objectives To evaluate the impact of preoperative anemia and perioperative blood transfusion (PBT) on disease free (DFS) and overall survival (OS) of patients with head and neck squamous cell carcinoma (HNSCC). Methods Retrospective study of 354 patients primarily treated with surgery between 2006 and 2016. Cases were selected according to completeness and accuracy of available clinical data. Thus, a selection bias cannot be excluded. Patients who received PBT were identified by our controlling department and verified by our blood bank data base. Results Both, preoperative anemia and PBT significantly decreased OS in univariate analysis. Although PBT was needed more frequently by older patients in worse physical conditions with more advanced HNSCC, subgroup analysis also demonstrate a profoundly negative effect of PBT on OS in younger patients and early stage HNSCC. According to a restrictive transfusion policy at our hospital the transfusion rate was comparably low. We could not verify increasing effects of PBT on cancer recurrence rates as it was previously shown. Discussion Preoperative anemia is the most common paraneoplastic syndrome in HNSCC. Despite its devastating prognostic effect we suggest a restrictive transfusion policy whenever possible. Our data also show that anemia as an independent prognostic factor in head and neck surgical oncology is defined not only by low hemoglobin concentrations but low red blood cell counts as well

Effect of improved atmospheric opacities in modelling sub-Neptunes

Aims. We investigate the impact of updated atmospheric mean opacity input values on modelled transit radius and the distribution of interior layer mass fractions. Methods. We developed and applied a coupled interior-atmosphere model. Our straightforward semi-grey calculation of atmospheric temperature enables us to perform thousands of model realisations in a Monte Carlo approach to address potential degeneracies in interior and atmospheric mass fraction. Our main constraints are planetary mass and radius from which our model infers distributions of the internal structure of exoplanetary classes ranging from Super-Earth to Mini-Neptune. We varied the relative masses of gas, envelope, mantle, and core layers subject to constraints on the bulk density from observations, and investigated the effect of updating atmospheric mean opacities. Results. First, we validate our model output with observed temperature profiles for modern Neptune. We can reproduce the basic features in the middle atmosphere but not the temperature inversion in the upper layers, which is likely because our model lacks aerosol heating. Calculated interiors are generally consistent with modern Neptune. Second, we compare with the well-studied object GJ 1214 b and obtain results that are broadly consistent with previous findings; they suggest correlations between modelled gas, water, and core mass fractions, although these are generally weak. Updating the opacities leads to a change on the order of a few percent in the modelled transit radius. This is comparable in magnitude to the planned accuracy of the PLATO data for planetary radius, suggesting that the opacity update in the model is important to implement

Machine learning inference of the interior structure of low-mass exoplanets

We explore the application of machine learning based on mixture density neural networks (MDNs) to the interior characterization of low-mass exoplanets up to 25 Earth masses constrained by mass, radius, and fluid Love number $k_2$. We create a dataset of 900$\:$000 synthetic planets, consisting of an iron-rich core, a silicate mantle, a high-pressure ice shell, and a gaseous H/He envelope, to train a MDN using planetary mass and radius as inputs to the network. For this layered structure, we show that the MDN is able to infer the distribution of possible thicknesses of each planetary layer from mass and radius of the planet. This approach obviates the time-consuming task of calculating such distributions with a dedicated set of forward models for each individual planet. While gas-rich planets may be characterized by compositional gradients rather than distinct layers, the method presented here can be easily extended to any interior structure model. The fluid Love number $k_2$ bears constraints on the mass distribution in the planets' interior and will be measured for an increasing number of exoplanets in the future. Adding $k_2$as an input to the MDN significantly decreases the degeneracy of the possible interior structures.Comment: 14 pages, 7 figures, accepted for publication in Ap

Abundance of water oceans on high-density exoplanets from coupled interior-atmosphere modeling

Liquid water is generally assumed to be the an essential factor for the emergence of life, and so a major goal in exoplanet science is the search for planets with water oceans. On terrestrial planets, the silicate mantle is a large source of water, which can be outgassed into the atmosphere via volcanism. Outgassing is subject to a series of feedback processes between atmosphere and interior, which continually shape both atmospheric composition, pressure, and temperature, as well as interior dynamics [1,2]. We present the results of an extensive parameter study, where we use a newly developed 1D numerical model to simulate the coupled evolution of the atmosphere and interior of terrestrial exoplanets up to 5 Earth masses around Sun-like stars, with internal structures ranging from Moon-to Mercury-like. The model accounts for the main mechanisms controlling the global-scale, long-term evolution of stagnant-lid rocky planets (i.e. bodies without plate tectonics), and it includes a large number of atmosphere-interior feedback processes, such as a CO2 weathering cycle, volcanic outgassing, a water cycle between ocean and atmosphere, greenhouse heating, as well as the influence of a potential primordial H2 atmosphere, which can be lost through escape processes.We find that a significant majority of high-density exoplanets(i.e. Mercury-like planets with large metallic cores) are able to outgas and sustain water on their surface. In contrast, most planets with intermediate, Earth-like densities either transition into a runaway greenhouse regime due to strong CO2 outgassing,or retain part of their primordial atmosphere, which prevents water from being outgassed. This suggests that high-density planets could be the most promising targets when searching for suitable candidates for hosting liquid water. [1] Tosi, N. et al. The habitability of a stagnant-lid earth. A&A605, A71 (2017). [2] Noack, L., Rivoldini, A. & Van Hoolst, T. Volcanism and outgassing of stagnant-lid planets: Implications for the habitable zone. Physics of the Earth and Planetary Interiors 269, 40-57 (2017)

Water oceans on high-density, stagnant-lid exoplanets from coupled interior-atmosphere modeling

Liquid water is generally assumed to be the most important factor for the emergence of life, and so a major goal in exoplanet science is the search for planets with water oceans. On terrestrial planets, the silicate mantle is a large source of water, which can be outgassed into the atmosphere via volcanism. Outgassing is subject to a series of feedback processes between atmosphere and interior, which continually shape both atmospheric composition, pressure, and temperature, as well as interior dynamics. We present the results of an extensive parameter study, where we use a newly developed 1D numerical model to simulate the coupled evolution of the atmosphere and interior of terrestrial exoplanets up to 5 Earth masses around Sun-like stars, with internal structures ranging from Moon- to Mercury-like. The model accounts for the main mechanisms controlling the global-scale, long-term evolution of stagnant-lid rocky planets (i.e. bodies without plate tectonics), and it includes a large number of atmosphere-interior feedback processes, such as a CO2 weathering cycle, volcanic outgassing, a water cycle between ocean and atmosphere, greenhouse heating, as well as the influence of a potential primordial H2 atmosphere, which can be lost through escape processes. We find that a significant majority of high-density exoplanets (i.e. Mercury-like planets with large cores) are able to outgas and sustain water on their surface. In contrast, most planets with intermediate, Earth-like densities either transition into a runaway greenhouse regime due to strong CO2 outgassing, or retain part of their primordial atmosphere, which prevents water from being outgassed. This suggests that high-density planets could be the most promising targets when searching for suitable candidates for hosting liquid water