Evolution and functional cross-talk of protein post-translational modifications

Protein post-translational modifications (PTMs) allow the cell to regulate protein activity and play a crucial role in the response to changes in external conditions or internal states. Advances in mass spectrometry now enable proteome wide characterization of PTMs and have revealed a broad functional role for a range of different types of modifications. Here we review advances in the study of the evolution and function of PTMs that were spurred by these technological improvements. We provide an overview of studies focusing on the origin and evolution of regulatory enzymes as well as the evolutionary dynamics of modification sites. Finally, we discuss different mechanisms of altering protein activity via post-translational regulation and progress made in the large-scale functional characterization of PTM function

Incidence of lymph node metastases in clinical early-stage mucinous and seromucinous ovarian carcinoma: a retrospective cohort study

Objective: The use of lymph node sampling during staging procedures in clinical early-stage mucinous ovarian carcinoma (MOC) is an ongoing matter of debate. Furthermore, the incidence of lymph node metastases (LNM) in MOC in relation to tumour grade (G) is unknown. We aimed to determine the incidence of LNM in clinical early-stage MOC per tumour grade. Design: Retrospective study with data from the Dutch Pathology Registry (PALGA). Setting: The Netherlands, 2002–2012. Population or sample: Patients with MOC. Methods: Histology reports on patients with MOC diagnosed in the Netherlands between 2002 and 2012 were obtained from PALGA. Reports were reviewed for diagnosis, tumour grade and presence of LNM. Clinical data, surgery reports and radiology reports of patients with LNM were retrieved from hospital files. Main outcome measures: Incidence of LNM, disease-free survival (DFS). Results: Of 915 patients with MOC, 426 underwent lymph node sampling. Cytoreductive surgery was performed in 267 patients. The other 222 patients received staging without lymph node sampling. In eight of 426 patients, LNM were discovered by sampling. In four of 190 (2.1%) patients with G1 MOC, LNM were present, compared with one of 115 (0.9%) patients with G2 MOC and three of 22 (13.6%) patients with G3 MOC. Tumour grade was not specified in 99 patients. Patients with clinical early-stage MOC had no DFS benefit from lymph node sampling. Conclusions: LNM are rare in early-stage G1 and G2 MOC without clinical suspicion of LNM. Therefore, lymph node sampling can be omitted in these patients

Modelling Eco-Driving Support System for Microscopic Traffic Simulation

Microscopic traffic simulation is an ideal tool for investigating the network level impacts of eco-driving in different networks and traffic conditions, under varying penetration rates and driver compliance rates. The reliability of the traffic simulation results however rely on the accurate representation of the simulation of the driver support system and the response of the driver to the eco-driving advice, as well as on a realistic modelling and calibration of the driver’s behaviour. The state-of-the-art microscopic traffic simulation models however exclude detailed modelling of the driver response to eco-driver support systems. This paper fills in this research gap by presenting a framework for extending state-of-the-art traffic simulation models with sub models for drivers’ compliance to advice from an advisory eco-driving support systems. The developed simulation framework includes among others a model of driver’s compliance with the advice given by the system, a gear shifting model and a simplified model for estimating vehicles maximum possible acceleration. Data from field operational tests with a full advisory eco-driving system developed within the ecoDriver project was used to calibrate the developed compliance models. A set of verification simulations used to illustrate the effect of the combination of the ecoDriver system and drivers’ compliance to the advices are also presented

Maximum Entropy Limit of Small-scale Magnetic Field Fluctuations in the Quiet Sun

The observed magnetic field on the solar surface is characterized by a very complex spatial and temporal behavior. Although feature-tracking algorithms have allowed us to deepen our understanding of this behavior, subjectivity plays an important role in the identification and tracking of such features. In this paper, we continue studies Gorobets, A. Y., Borrero, J. M., & Berdyugina, S. 2016, ApJL, 825, L18 of the temporal stochasticity of the magnetic field on the solar surface without relying either on the concept of magnetic features or on subjective assumptions about their identification and interaction. We propose a data analysis method to quantify fluctuations of the line-of-sight magnetic field by means of reducing the temporal field's evolution to the regular Markov process. We build a representative model of fluctuations converging to the unique stationary (equilibrium) distribution in the long time limit with maximum entropy. We obtained different rates of convergence to the equilibrium at fixed noise cutoff for two sets of data. This indicates a strong influence of the data spatial resolution and mixing-polarity fluctuations on the relaxation process. The analysis is applied to observations of magnetic fields of the relatively quiet areas around an active region carried out during the second flight of the Sunrise/IMaX and quiet Sun areas at the disk center from the Helioseismic and Magnetic Imager on board the Solar Dynamics Observatory satellite.Comment: 11 pages, 5 figures, The Astrophysical Journal Supplement Series (accepted

CART - a chemical annotation retrieval toolkit

MOTIVATION: Data on bioactivities of drug-like chemicals is rapidly accumulating in public repositories, creating new opportunities for research in computational systems pharmacology. However, integrative analysis of these data sets is difficult due to prevailing ambiguity between chemical names and identifiers and a lack of cross-references between databases. RESULTS: To address this challenge, we have developed CART, a Chemical Annotation Retrieval Toolkit. As a key functionality, it matches an input list of chemical names into a comprehensive reference space to assign unambiguous chemical identifiers. In this unified space, bioactivity annotations can be easily retrieved from databases covering a wide variety of chemical effects on biological systems. Subsequently, CART can determine annotations enriched in the input set of chemicals and display these in tabular format and interactive network visualizations, thereby facilitating integrative analysis of chemical bioactivity data

Characterization of horizontal flows around solar pores from high-resolution time series of images

Though there is increasing evidence linking the moat flow and the Evershed flow along the penumbral filaments, there is not a clear consensus regarding the existence of a moat flow around umbral cores and pores, and the debate is still open. Solar pores appear to be a suitable scenario to test the moat-penumbra relation as evidencing the direct interaction between the umbra and the convective plasma in the surrounding photosphere, without any intermediate structure in between. The present work studies solar pores based on high resolution ground-based and satellite observations. Local correlation tracking techniques have been applied to different-duration time series to analyze the horizontal flows around several solar pores. Our results establish that the flows calculated from different solar pore observations are coherent among each other and show the determinant and overall influence of exploding events in the granulation around the pores. We do not find any sign of moat-like flows surrounding solar pores but a clearly defined region of inflows surrounding them. The connection between moat flows and flows associated to penumbral filaments is hereby reinforced by this work.Comment: 10 pages, 10 figures, Accepted for publication in Astronomy and Astrophysics

Kinematics of Magnetic Bright Features in the Solar Photosphere

Convective flows are known as the prime means of transporting magnetic fields on the solar surface. Thus, small magnetic structures are good tracers of the turbulent flows. We study the migration and dispersal of magnetic bright features (MBFs) in intergranular areas observed at high spatial resolution with Sunrise/IMaX. We describe the flux dispersal of individual MBFs as a diffusion process whose parameters are computed for various areas in the quiet Sun and the vicinity of active regions from seeing-free data. We find that magnetic concentrations are best described as random walkers close to network areas (diffusion index, gamma=1.0), travelers with constant speeds over a supergranule (gamma=1.9-2.0), and decelerating movers in the vicinity of flux emergence and/or within active regions (gamma=1.4-1.5). The three types of regions host MBFs with mean diffusion coefficients of 130 km^2/s, 80-90 km^2/s, and 25-70 km^2/s, respectively. The MBFs in these three types of regions are found to display a distinct kinematic behavior at a confidence level in excess of 95%.Comment: 8 pages, 4 figure