39 research outputs found

    Brain Radiation Information Data Exchange (BRIDE): Integration of experimental data from low-dose ionising radiation research for pathway discovery

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    Background: The underlying molecular processes representing stress responses to low-dose ionising radiation (LDIR) in mammals are just beginning to be understood. In particular, LDIR effects on the brain and their possible association with neurodegenerative disease are currently being explored using omics technologies. Results: We describe a light-weight approach for the storage, analysis and distribution of relevant LDIR omics datasets. The data integration platform, called BRIDE, contains information from the literature as well as experimental information from transcriptomics and proteomics studies. It deploys a hybrid, distributed solution using both local storage and cloud technology. Conclusions: BRIDE can act as a knowledge broker for LDIR researchers, to facilitate molecular research on the systems biology of LDIR response in mammals. Its flexible design can capture a range of experimental information for genomics, epigenomics, transcriptomics, and proteomics. The data collection is available at:

    Evaluating privacy-preserving record linkage using cryptographic long-term keys and multibit trees on large medical datasets.

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    Background: Integrating medical data using databases from different sources by record linkage is a powerful technique increasingly used in medical research. Under many jurisdictions, unique personal identifiers needed for linking the records are unavailable. Since sensitive attributes, such as names, have to be used instead, privacy regulations usually demand encrypting these identifiers. The corresponding set of techniques for privacy-preserving record linkage (PPRL) has received widespread attention. One recent method is based on Bloom filters. Due to superior resilience against cryptographic attacks, composite Bloom filters (cryptographic long-term keys, CLKs) are considered best practice for privacy in PPRL. Real-world performance of these techniques using large-scale data is unknown up to now. Methods: Using a large subset of Australian hospital admission data, we tested the performance of an innovative PPRL technique (CLKs using multibit trees) against a gold-standard derived from clear-text probabilistic record linkage. Linkage time and linkage quality (recall, precision and F-measure) were evaluated. Results: Clear text probabilistic linkage resulted in marginally higher precision and recall than CLKs. PPRL required more computing time but 5 million records could still be de-duplicated within one day. However, the PPRL approach required fine tuning of parameters. Conclusions: We argue that increased privacy of PPRL comes with the price of small losses in precision and recall and a large increase in computational burden and setup time. These costs seem to be acceptable in most applied settings, but they have to be considered in the decision to apply PPRL. Further research on the optimal automatic choice of parameters is needed

    Noise Contributions in an Inducible Genetic Switch: A Whole-Cell Simulation Study

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    Stochastic expression of genes produces heterogeneity in clonal populations of bacteria under identical conditions. We analyze and compare the behavior of the inducible lac genetic switch using well-stirred and spatially resolved simulations for Escherichia coli cells modeled under fast and slow-growth conditions. Our new kinetic model describing the switching of the lac operon from one phenotype to the other incorporates parameters obtained from recently published in vivo single-molecule fluorescence experiments along with in vitro rate constants. For the well-stirred system, investigation of the intrinsic noise in the circuit as a function of the inducer concentration and in the presence/absence of the feedback mechanism reveals that the noise peaks near the switching threshold. Applying maximum likelihood estimation, we show that the analytic two-state model of gene expression can be used to extract stochastic rates from the simulation data. The simulations also provide mRNA–protein probability landscapes, which demonstrate that switching is the result of crossing both mRNA and protein thresholds. Using cryoelectron tomography of an E. coli cell and data from proteomics studies, we construct spatial in vivo models of cells and quantify the noise contributions and effects on repressor rebinding due to cell structure and crowding in the cytoplasm. Compared to systems without spatial heterogeneity, the model for the fast-growth cells predicts a slight decrease in the overall noise and an increase in the repressors rebinding rate due to anomalous subdiffusion. The tomograms for E. coli grown under slow-growth conditions identify the positions of the ribosomes and the condensed nucleoid. The smaller slow-growth cells have increased mRNA localization and a larger internal inducer concentration, leading to a significant decrease in the lifetime of the repressor–operator complex and an increase in the frequency of transcriptional bursts

    Insight to the numerical modeling of the lateral response of caisson foundation to static and cyclic loading

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    Στην παρούσα διπλωματική εργασία επεκτείνονται και συγκρίνονται 2 σημαντικά αριθμητικά εργαλεία για την ανάλυση φρεάτων θεμελίωσης υπο στατική και ανακυκλιζόμενη φόρτιση, ένα «μακρο-στοιχείο» και ένα μη γραμμικό τετρα-ελατηριωτό προσομοίωμα. Ορίζονται αναλυτικά οι επιφάνειες διαρροής στο γενικευμένο χώρο φόρτισης M-Q-Nγια την περίπτωση γεωμετρικών μη-γραμμικοτήτων στη διεπιφάνεια εδάφους θεμελίου και συγκρίνονται με τις αντίστοιχες της θεώρησης πλήρους επαφής. Οι αναλυτικές εκφράσεις είναι έτοιμες προς ενσωμάτωση σε ένα ενιαίο μαθηματικό εργαλείο (το λεγόμενο «μακρο-στοιχείο»), που περιλαμβάνει 4 συνιστώσες: α) την ελαστική συμπεριφορά, β) τις επιφάνειες διαρροής, γ) ενα κατάλληλο νόμο πλαστικής ροής και δ) ένα κατάλληλο νόμο κράτυνσης. Στο δεύτερο μέρος της εργασίας βαθμονομείται εκτενώς το ελατηριωτό προσομοιώμα BWGG [Gerolymos&Gazetas, 2006], τόσο σε στατική όσο και ανακυκλιζόμενη φόρτιση, ώστε τελικώς μπορεί να αναπαράγει ρεαλιστικά την απόκριση άκαμπτων φρεάτων θεμελίωσης. Η βαθμονόμηση και των 2 προσομοιωμάτων βασίζεται σε 3-διάστατες αναλύσεις πεπερασμένων στοιχείων.This diploma thesis deals with the extension and comparison of two numerical models for the lateral response of caisson foundations under static monotonic and cyclic loading; a “macro-element” and a nonlinear 4-spring Winkler model. The yield surfaces of caisson foundations under combined M-Q-N loading are derived in the case of geometric nonlinearities at the soil-caisson interface, and these are compared to the equivalent bonded interface ones. The new analytical expressions are ready to be incorporated in a unified mathematical tool (“macro-element”) which includes 4 components: a) the elastic behaviour of the soil-foundation system, b) the yield surfaces under combined loading, c) a proper plastic flow rule and d) a proper hardening law. In the second part of the thesis, the BWGG Winkler model [Gerolymos&Gazetas, 2006] is extensively calibrated to static and cyclic loading. The calibration of both models is based on 3-dimensional Finite Element analyses.Κωνσταντίνος Δ. Καραπιπέρη

    Lithographie par faisceaux d'ions : simulations et résultats expérimentaux

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    The advantages offered by Ion Beam Lithography compared to other lithographic techniques in use today are discussed. The lithographic resolution achievable with light (H+) and heavy (Ga+) ions is studied experimentally. Patterns of dimensions less than 100 nm are transferred in a resist (PMMA) by exposure to light and heavy ions through special thin-membrane masks. The effect of recoil atoms created by focused heavy ion beams in the resist on lithographic resolution is demonstrated with the aid of a computer simulation program of ionstopping in amorphous materials. Computer-simulated developed profiles in resist after ion exposure are pre sented. The use of focused ion-beam systems employing liquid metal sources for lithographic applications is discussed.Cet article décrit une nouvelle technique de lithographie qui utilise des faisceaux d'ions. Les avantages de cette technique sont discutés, et comparés à ceux présentés par d'autres méthodes lithographiques couramment utilisées. La résolution de la lithographie ionique est étudiée expérimentalement par irradiation de résine PMMA à l'aide d'ions légers (H+) et d'ions lourds (Ga+). Des motifs géométriques de dimensions inférieures à 100 nm ont été transférés dans la résine (PMMA) à partir de masques adaptés (membranes minces à trous). L'effet, sur la résolution, des atomes de recul créés pendant l'irradiation est mis en évidence à l'aide d'un programme de simulation du freinage des ions dans la matière amorphe. Des profils de développement de la résine après irradiation aux ions Ga+ sont simulés sur ordinateur. L'utilisation, pour la lithographie, de machines ioniques à sources d'ions à métaux liquides est discutée

    Lithographie par faisceaux d'ions : simulations et résultats expérimentaux

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    Cet article décrit une nouvelle technique de lithographie qui utilise des faisceaux d'ions. Les avantages de cette technique sont discutés, et comparés à ceux présentés par d'autres méthodes lithographiques couramment utilisées. La résolution de la lithographie ionique est étudiée expérimentalement par irradiation de résine PMMA à l'aide d'ions légers (H+) et d'ions lourds (Ga+). Des motifs géométriques de dimensions inférieures à 100 nm ont été transférés dans la résine (PMMA) à partir de masques adaptés (membranes minces à trous). L'effet, sur la résolution, des atomes de recul créés pendant l'irradiation est mis en évidence à l'aide d'un programme de simulation du freinage des ions dans la matière amorphe. Des profils de développement de la résine après irradiation aux ions Ga+ sont simulés sur ordinateur. L'utilisation, pour la lithographie, de machines ioniques à sources d'ions à métaux liquides est discutée

    A tutorial on blocking methods for privacy-preserving record linkage

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    In this paper, we first present five state-of-the-art private blocking methods which rely mainly on random strings, clustering, and public reference sets. We emphasize on the drawbacks of these methods, and then, we present our L-fold redundant blocking scheme, that relies on the Locality-Sensitive Hashing technique for identifying similar records. These records have undergone an anonymization transformation using a Bloom filter-based encoding technique. Finally, we perform an experimental evaluation of all these methods and present the results. © Springer International Publishing Switzerland 2016

    Selective epitaxial growth in silicon on insulator: Planarity and mass flow

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    Seeded zone-melt recrystallization using a dual electron beam system has been performed on silicon-on-insulator material, which was prepared with single-crystal silicon filling of the seed windows by selective epitaxial growth. The crystal quality has been assessed by a variety of microscopic techniques, and it is shown that single-crystal films 0.5-1.0 μm thick over 1.0 μm of isolating oxide may be prepared by this method. These films have considerably less lateral variation in thickness than standard material, in which the windows are not so filled. The filling method is suitable for both single- and multiple-layer silicon-on-insulator, and gives the advantages of excellent layer uniformity after recrystallization and improved planarity of the whole chip structure. Experiments using various amounts of seed window filling have shown that the lateral variations of silicon film thickness seen in unplanarized material are due to stress relief in the cap oxide when the silicon film is molten, rather than the effect previously postulated in which they were assumed to be due to the contraction of silicon on melting
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