Editorial : Autophagy : from big data to physiological significance

Autophagy is a fundamental catabolic process where cytoplasmic components are sequestered into double-membrane vesicles called autophagosomes, which then fuse with lysosomes and their content is degraded. Our knowledge about autophagy sharply increased during the last decade. This significant progress helped us to understand better the molecular mechanisms of autophagy and to elucidate its role in health and disease. This special issue contains a collection of three original research papers and 12 review articles covering a broad range of topics highlighting how big data and screening approaches can help toward uncovering the molecular mechanisms of autophagy

Coarse Grained Computations for a Micellar System

We establish, through coarse-grained computation, a connection between traditional, continuum numerical algorithms (initial value problems as well as fixed point algorithms) and atomistic simulations of the Larson model of micelle formation. The procedure hinges on the (expected) evolution of a few slow, coarse-grained mesoscopic observables of the MC simulation, and on (computational) time scale separation between these and the remaining "slaved", fast variables. Short bursts of appropriately initialized atomistic simulation are used to estimate the (coarse-grained, deterministic) local dynamics of the evolution of the observables. These estimates are then in turn used to accelerate the evolution to computational stationarity through traditional continuum algorithms (forward Euler integration, Newton-Raphson fixed point computation). This "equation-free" framework, bypassing the derivation of explicit, closed equations for the observables (e.g. equations of state) may provide a computational bridge between direct atomistic / stochastic simulation and the analysis of its macroscopic, system-level consequences

Coarse-Grained Kinetic Computations for Rare Events: Application to Micelle Formation

We discuss a coarse-grained approach to the computation of rare events in the context of grand canonical Monte Carlo (GCMC) simulations of self-assembly of surfactant molecules into micelles. The basic assumption is that the {\it computational} system dynamics can be decomposed into two parts -- fast (noise) and slow (reaction coordinates) dynamics, so that the system can be described by an effective, coarse grained Fokker-Planck (FP) equation. While such an assumption may be valid in many circumstances, an explicit form of FP equation is not always available. In our computations we bypass the analytic derivation of such an effective FP equation. The effective free energy gradient and the state-dependent magnitude of the random noise, which are necessary to formulate the effective Fokker-Planck equation, are obtained from ensembles of short bursts of microscopic simulations {\it with judiciously chosen initial conditions}. The reaction coordinate in our micelle formation problem is taken to be the size of a cluster of surfactant molecules. We test the validity of the effective FP description in this system and reconstruct a coarse-grained free energy surface in good agreement with full-scale GCMC simulations. We also show that, for very small clusters, the cluster size seizes to be a good reaction coordinate for a one-dimensional effective description. We discuss possible ways to improve the current model and to take higher-dimensional coarse-grained dynamics into account

Vignette Equivalence and Response Consistency : The case of job satisfaction

Preprin

Image and Reality: the Case of Job Satisfaction

This study makes a distinction between two types of utility. Experienced utility is defined as the job satisfaction derived from the present job, estimated by using a subjective evaluation of job satisfaction. Anticipated utility is defined as the individual’s anticipated job satisfaction before starting the job and it is studied by using a stated preference methodology known as conjoint analysis. The results suggest that the two utility concepts are different. Information about experienced utility is useful for the evaluation of well-being policies and the welfare effects of various employer strategies. Anticipated utility provides knowledge about the job search process.European Commission, Fifth Framework Programme "Improving Human Potential" (contract number: HPSE-CT-2002-00143)

Biosynthesis of amine oxides using calcium-alginate immobilized hog liver microsomes : an evaluation of process and reactor design

An evaluation of the biocatalytic ability and the potential utilization of Calcium-alginate immobilized hepatic microsomes (beads) for the biosynthesis of amine oxides has been performed, To accomplish this task, the following three areas Were investigated: immobilization, catalytic biooxidation ability, and reactor configurations. Immobilization was found to result in higher yields over free microsomes at the expense of higher cofactor requirements. Refrigerated drying of immobilized micro-somes appears to be a better storage technique than wet storage in buffer. Smaller beads resulted in higher rates than larger beads, but size did not affect the overall yield. Chlorpromazine (CPZ), diphenylamine (DPA) and 4-hydroxy-2,2,6,6-tetramethylpiperidine (TMP) were used as substrates to demonstrate the catalytic ability of microsomal enzymes to biooxidize tertiary and hindered secondary amines. The biooxidation of all three compounds to their oxides, by hog liver microsomes, required the presence of NADPH and oxygen. CPZ was converted to its N-oxide while, DPA and TMP were converted to nitroxide free radicals. Optimal reaction requirements for each substrate were established, NADPH is a reaction limiting factor for the oxidation of all three compounds. Biooxidation of the substrates increased, up to two-fold, by addition of n-tylamine, suggesting that mixed function amine oxidase (MFAO) is responsible for the N-oxidation of the amines. The progress of the previously described reactions was followed by means of oxygen uptake and HPLC. The identification of CPZ N-oxide was done using NMR, HPLC and TLC. ESR spectroscopy was used to verify the formation of nitroxide free radicals. A recirculation flow reactor is recommended for large scale production with immobilized whole microsomes. This configuration helps to maintain the physical integrity of the biocatalyst over longer reaction periods. The recirculation flow reactor also gives higher yields than a batch reactor

Subsurface fault imaging using crosshole tomographic methods

Πειράματα σεισμικής τομογραφίας μεταξύ γεωτρήσεων διεξήχθησαν στην ευρύτερη αστική περιοχή του Δήμου Άνω Λιοσίων με σκοπό την λεπτομερή απεικόνιση της υπεδαφικής γεωλογικο-τεκτονικής δομής στις θέσεις έρευνας. Τα σεισμικά δεδομένα έτυχαν -ψηφιακής επεξεργασίας με σύγχρονο λογισμικό πακέτο όπου χρησιμοποιήθηκε η τεχνική της ταυτόχρονης επαναληπτικής ανακατασκευής (SIRT) για την αντιστροφή των χρόνων διαδρομής των πρώτων σεισμικών αφίξεων. Τα αποτελέσματα της έρευνας είναι υψηλής ανάλυσης απεικονίσεις του πεδίου σεισμικών ταχυτήτων στον μεταξύ των γεωτρήσεων χώρο. Οι απεικονίσεις παρέχουν υψηλής ευκρίνειας ταχείες πλευρικές και σε βάθος μεταβολές της σεισμικής ταχύτητας μη δυνάμενες να παρατηρηθούν με τις συμβατικές γεωφυσικές μεθόδους επιφανείας. Τα αποτελέσματα επιβεβαιώνουν το γεγονός ότι η σεισμική τομογραφία μεταξύ γεωτρήσεων είναι μία εύχρηστη και δυναμική τεχνική για την απεικόνιση σύνθετων υπεδαφικών δομών χρήσιμη στην τεχνική γεωλογία και στα έργα πολιτικού μηχανικού. Η δυναμικότητα της μεθόδου οφείλεται κατά κύριο λόγο στο γεγονός ότι η υψηλή διακριτική της ικανότητα διατηρείται η ίδια καθώς το βάθος έρευνας αυξάνει λόγω της διατήρησης του υψηλού συχνοτικού περιεχόμενου της διαδιδόμενης ενέργειας σε αντίθεση με τις συμβατικές μεθόδους επιφανείας όπου η απώλεια των υψηλών συχνοτήτων είναι ταχεία λόγω της απορρόφησης.Crosshole seismic tomography experiments were performed to image the subsurface structure between pairs of wells in three locations at Ano Liosia Municipality. Seismic caps were used as downhole sources and a 24-channel geophone cable provided the downhole receivers. The crosshole data were processed with a SIRT traveltime transmission tomography package to produce a velocity model. The crosshole velocity section exhibits rapid lateral and vertical velocity changes that are not resolved by surface methods. The results indicate that crosshole tomography can potentially be used to image steeply dipping beds or complex structures, such as small faults or cavities