Habitable Climate Scenarios for Proxima Centauri b With a Dynamic Ocean

The nearby exoplanet Proxima Centauri b will be a prime future target for characterization, despite questions about its retention of water. Climate models with static oceans suggest that an Earth-like Proxima b could harbor a small dayside region of surface liquid water at fairly warm temperatures despite its weak instellation. We present the first 3-dimensional climate simulations of Proxima b with a dynamic ocean. We find that an ocean-covered Proxima b could have a much broader area of surface liquid water but at much colder temperatures than previously suggested, due to ocean heat transport and depression of the freezing point by salinity. Elevated greenhouse gas concentrations do not necessarily produce more open ocean area because of possible dynamic regime transitions. For an evolutionary path leading to a highly saline present ocean, Proxima b could conceivably be an inhabited, mostly open ocean planet dominated by halophilic life. For an ocean planet in 3:2 spin-orbit resonance, a permanent tropical waterbelt exists for moderate eccentricity. Simulations of Proxima Centauri b may also be a model for the habitability of planets receiving similar instellation from slightly cooler or warmer stars, e.g., in the TRAPPIST-1, LHS 1140, GJ 273, and GJ 3293 systems.Comment: Submitted to Astrobiology; 38 pages, 12 figures, 5 table

Crura ultrastructural alterations in patients with hiatal hernia: a pilot study

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Emergent bipartiteness in a society of knights and knaves

We propose a simple model of a social network based on so-called knights-and-knaves puzzles. The model describes the formation of networks between two classes of agents where links are formed by agents introducing their neighbours to others of their own class. We show that if the proportion of knights and knaves is within a certain range, the network self-organizes to a perfectly bipartite state. However, if the excess of one of the two classes is greater than a threshold value, bipartiteness is not observed. We offer a detailed theoretical analysis for the behaviour of the model, investigate its behaviou r in the thermodynamic limit, and argue that it provides a simple example of a topology-driven model whose behaviour is strongly reminiscent of a first-order phase transitions far from equilibrium.Comment: 12 pages, 5 figure

Exact sampling of graphs with prescribed degree correlations

Many real-world networks exhibit correlations between the node degrees. For instance, in social networks nodes tend to connect to nodes of similar degree and conversely, in biological and technological networks, high-degree nodes tend to be linked with low-degree nodes. Degree correlations also affect the dynamics of processes supported by a network structure, such as the spread of opinions or epidemics. The proper modelling of these systems, i.e., without uncontrolled biases, requires the sampling of networks with a specified set of constraints. We present a solution to the sampling problem when the constraints imposed are the degree correlations. In particular, we develop an exact method to construct and sample graphs with a specified joint-degree matrix, which is a matrix providing the number of edges between all the sets of nodes of a given degree, for all degrees, thus completely specifying all pairwise degree correlations, and additionally, the degree sequence itself. Our algorithm always produces independent samples without backtracking. The complexity of the graph construction algorithm is ${\mathcal{O}}({NM})$ where N is the number of nodes and M is the number of edges

Combined Targeting of Pathogenetic Mechanisms in Pancreatic Neuroendocrine Tumors Elicits Synergistic Antitumor Effects

Buparlisib; Combination therapy; Primary human tumoroidsBuparlisib; Terapia de combinación; Tumoroides humanos primariosBuparlisib; Teràpia combinada; Tumoroides humans primarisPancreatic neuroendocrine neoplasms (PanNENs) are the second most common malignancy of the pancreas. Surgery remains the only curative treatment for localized disease. For patients with inoperable advanced or metastatic disease, few targeted therapies are available, but their efficacy is unpredictable and variable. Exploiting prior knowledge on pathogenetic processes involved in PanNEN tumorigenesis, we tested buparlisib (PI3K inhibitor) and ribociclib (CDK4/6 inhibitor), as single agents or in combination, in different preclinical models. First, we used cell lines representative of well-differentiated (INS-1E, NT-3) and poorly differentiated (BON-1) PanNENs. The combination of buparlisib with ribociclib reduced the proliferation of 2D and 3D spheroid cultures more potently than the individual drugs. Buparlisib, but not ribociclib, induced apoptosis. The anti-proliferative activity of the drugs correlated with downstream target inhibition at mRNA and protein levels. We then tested the drugs on primary islet microtissues from a genetic PanNET animal model (Men1-defective mice) and from wild-type mice: the drug combination was effective against the former without altering islet cell physiology. Finally, we treated PanNET patient-derived islet-like 3D tumoroids: the combination of buparlisib with ribociclib was effective in three out of four samples. Combined targeting of PI3K and CDK4/6 is a promising strategy for PanNENs spanning various molecular and histo-pathological features.This work was supported by the German Research Foundation (Deutsche Forschungsgemeinschaft-DFG) within the CRC/Transregio 205/2, project number 314061271-TRR 205 (to NSP); and by the Deutsche Krebshilfe (# 70113629 to NSP). Ilaria Marinoni was supported by Wilhelm Sander Stiftung (# 2017.073.2). Aurel Perren was supported by the Swiss Cancer Research Foundation (KFS-4227-08-2017)

Synchronization in dynamical networks with unconstrained structure switching

We provide a rigorous solution to the problem of constructing a structural evolution for a network of coupled identical dynamical units that switches between specified topologies without constraints on their structure. The evolution of the structure is determined indirectly, from a carefully built transformation of the eigenvector matrices of the coupling Laplacians, which are guaranteed to change smoothly in time. In turn, this allows to extend the Master Stability Function formalism, which can be used to assess the stability of a synchronized state. This approach is independent from the particular topologies that the network visits, and is not restricted to commuting structures. Also, it does not depend on the time scale of the evolution, which can be faster than, comparable to, or even secular with respect to the the dynamics of the units.Comment: 8 pages, 3 figures. arXiv admin note: text overlap with arXiv:1407.074

Effects of Extracorporeal Magnetic Stimulation in Fecal Incontinence.

Background: Fecal incontinence (FI) is a common condition that has devastating consequences for patients' QOL. In some patients, the conventional functional pelvic floor electrical stimulation has been effective but is an invasive and embarrassing treatment. The object of the study was to evaluate the feasibility of functional extracorporeal magnetic stimulation (FMS) in strengthening the pelvic floor muscles without an anal plug and the embarrassment of undressing. Materials and Methods: Thirty patients (26 female and 4 males) with FI were enrolled. All patients were assessed during a specialized coloproctology evaluation followed by endoanal ultrasonography and anorectal manometry. All patients underwent an FMS treatment once weekly for 8 weeks. Patients' outcome was assessed by the Cleveland Clinic Fecal Incontinence Score (CCFIS) and by the fecal incontinence QOL questionnaire (FIQL). Results: After 8 weeks, the number of solid and liquid stool leakage per week was significantly reduced (p<0.05) with a significant improvement of the CCFIS and of the FIQL (p<0.05). Moreover, the authors recorded a missed recruitment of the agonist and antagonists' defecation muscles. Conclusion: FMS is a safe, non-invasive and painless treatment for FI. It could be recommended for selected patients with non-surgical FI to ensure a rapid clinical improvement