Mapping the Space of Genomic Signatures

We propose a computational method to measure and visualize interrelationships among any number of DNA sequences allowing, for example, the examination of hundreds or thousands of complete mitochondrial genomes. An "image distance" is computed for each pair of graphical representations of DNA sequences, and the distances are visualized as a Molecular Distance Map: Each point on the map represents a DNA sequence, and the spatial proximity between any two points reflects the degree of structural similarity between the corresponding sequences. The graphical representation of DNA sequences utilized, Chaos Game Representation (CGR), is genome- and species-specific and can thus act as a genomic signature. Consequently, Molecular Distance Maps could inform species identification, taxonomic classifications and, to a certain extent, evolutionary history. The image distance employed, Structural Dissimilarity Index (DSSIM), implicitly compares the occurrences of oligomers of length up to $k$ (herein $k=9$) in DNA sequences. We computed DSSIM distances for more than 5 million pairs of complete mitochondrial genomes, and used Multi-Dimensional Scaling (MDS) to obtain Molecular Distance Maps that visually display the sequence relatedness in various subsets, at different taxonomic levels. This general-purpose method does not require DNA sequence homology and can thus be used to compare similar or vastly different DNA sequences, genomic or computer-generated, of the same or different lengths. We illustrate potential uses of this approach by applying it to several taxonomic subsets: phylum Vertebrata, (super)kingdom Protista, classes Amphibia-Insecta-Mammalia, class Amphibia, and order Primates. This analysis of an extensive dataset confirms that the oligomer composition of full mtDNA sequences can be a source of taxonomic information.Comment: 14 pages, 7 figures. arXiv admin note: substantial text overlap with arXiv:1307.375

Adaptive strong-field control of chemical dynamics guided by three-dimensional momentum imaging.

Shaping ultrafast laser pulses using adaptive feedback can manipulate dynamics in molecular systems, but extracting information from the optimized pulse remains difficult. Experimental time constraints often limit feedback to a single observable, complicating efforts to decipher the underlying mechanisms and parameterize the search process. Here we show, using two strong-field examples, that by rapidly inverting velocity map images of ions to recover the three-dimensional photofragment momentum distribution and incorporating that feedback into the control loop, the specificity of the control objective is markedly increased. First, the complex angular distribution of fragment ions from the nω+C2D4→C2D3++D interaction is manipulated. Second, isomerization of acetylene (nω+C2H2→C2H22+→CH2++C+) is controlled via a barrier-suppression mechanism, a result that is validated by model calculations. Collectively, these experiments comprise a significant advance towards the fundamental goal of actively guiding population to a specified quantum state of a molecule

Incorporating real time velocity map image reconstruction into closed-loop coherent control

We report techniques developed to utilize three-dimensional momentum information as feedback in adaptive femtosecond control of molecular dynamics. Velocity map imaging is used to obtain the three-dimensional momentum map of the dissociating ions following interaction with a shaped intense ultrafast laser pulse. In order to recover robust feedback information, however, the two-dimensional momentum projection from the detector must be inverted to reconstruct the full three-dimensional momentum of the photofragments. These methods are typically slow or require manual inputs and are therefore accomplished offline after the images have been obtained. Using an algorithm based upon an “onion-peeling” (also known as “back projection”) method, we are able to invert 1040 × 1054 pixel images in under 1 s. This rapid inversion allows the full photofragment momentum to be used as feedback in a closed-loop adaptive control scheme, in which a genetic algorithm tailors an ultrafast laser pulse to optimize a specific outcome. Examples of three-dimensional velocity map image based control applied to strong-field dissociation of CO and O2 are presented

HARMONIA: strategy of an integrated resilience assessment platform (IRAP) with available tools and geospatial services

The huge amount of the available data nowadays has raised some major challenges which are related to the storage, fusion, structure, streaming and processing of these data. In this paper, we present the development of a holistic framework, entitled HARMONIA, that encompasses State-of-The-Art solutions for the emerging issues related to Climate Change, natural and/or man-made hazards and urban/peri-urban risks. The Horizon 2020 HARMONIA project is developing an Integrated Resilience Assessment Platform (IRAP) which plans to provide targeted services for different groups of end-users. In particular, it will actively support urban decision-makers in strategic decisions and planning and citizens in facing daily effects and risks of Climate Change. Additionally, the platform will be a place to interconnect cities which end up facing similar Climate Change effects. HARMONIA IRAP leverages cuttingedge technologies (i.e., explainable Artificial Intelligence, Data Mining, multi-criteria analysis, dynamic programming) and services (ie., Virtual Machines, Containers) in order to provide solutions considering the complexity and diversity of extreme earth and non-earth data. In addition, this platform includes a Decision Support System providing early-warning feedback and recommendations to the end-users. In this way the HARMONIA IRAP design tends to address these challenges by offering the corresponding dynamic, scalable and robust mechanisms with the aim to provide useful integrated tools for the related users. Datacubes architecture, which is a major part of the IRAP, offers the opportunity to investigate more sophisticated correlations among the data and provide a more tangible representation of the extracted information

Pleural effusions in the dog. Etiology, Pathogenesis, Diagnosis and Treatment

Τα περιστατικά με συλλογή υγρού στην κοιλότητα του υπεζωκότα είναι σχετικά συχνά στην κλινική πράξη. Οι συλλογές αυτές οφείλονται σε πληθώρα αιτίων όπως είναι η δεξιά καρδιακή ανεπάρκεια, η περικαρδιακή νόσος, η υπολευκωματιναιμία, τα νεοπλάσματα των πνευμόνων ή των μεσοπνευμόνιων λεμφογαγγλίων, η διροφιλαρίαση, η διαφραγματοκήλη, η αιμορραγική διάθεση, οι τραυματισμοί του θωρακικού τοιχώματος, ενώ υπάρχουν και περιστατικά που η αιτιολογία τους είναι ασαφής, με αποτέλεσμα να χαρακτηρίζονται ως ιδιοπαθή. Η διάγνωση βασίζεται στις πληροφορίες από το ιστορικό, στα αποτελέσματα της κλινικής εξέτασης και ιδιαίτερα στα ευρήματα της ακρόασης και της επίκρουσης της θωρακικής κοιλότητας. Τα ακτινογραφήματα του θώρακα και η παρακέντηση της κοιλότητας του υπεζωκότα επιβεβαιώνουν τη συγκέντρωση του υγρού. Οι περαιτέρω διαγνωστικές δοκιμές (αιματολογική και βιοχημική εξέταση, γενική ανάλυση ούρων, ηλεκτροκαρδιογράφημα, υπερηχοτομογράφημα, φυσικοχημική εξέταση του υγρού της συλλογής, κ. ά) θα συμβάλουν στην αιτιολογική διάγνωση του νοσήματος. Η θεραπευτική αντιμετώπιση εξαρτάται από τη βαρύτητα του περιστατικού και το πρωτογενές αίτιο που προκάλεσε το νόσημα. Οι άρρωστοι σκύλοι που προσκομίζονται με έντονη δύσπνοια λόγω της συλλογής, υποβάλλονται άμεσα σε θωρακοκέντηση και αφαίρεση μέρους του υγρού με σκοπό την ανακούφισή τους. Επιπλέον, αντιμετωπίζεται το αίτιο που προκάλεσε τη συλλογή και όπου κρίνεται αναγκαίο, χορηγούνται ενδοφλέβια υγρά και ηλεκτρολύτες, αντιβιοτικά και ενδεχομένως τοποθετείται ενδοθωρακικός καθετήρας. Τέλος, σε υποτροπιάζουσεςσυλλογές επιχειρείται η πλευρόδεση.Accumulation of fluid (pleural effusion) in the pleural space of dogs is a relatively common clinical entity in the everyday practice. These can result from variable causes, such as right-sided heart failure, pericardial disease, hypoalbouminemia, neoplasia, heartworm disease, diaphragmatic hernia, bleeding disorders, traumatic or idiopathic causes. Diagnosis is based on history, clinical findings, laboratory tests, thoracocentesis, thoracic radiography and/or ultrasonography. Therapeutic approach depends on the etiology and the clinical condition of the affected dog. In dogs presented with severe respiratory distress, and after the confirmation of pleural effusion with thoracic radiography, thoracocentesis is performed to stabilize the animal's condition. If indicated, surgical management is attempted. Conservative therapy includes intravenous fluid and electrolyte replacement, antibiotics administration and chest tube placement in refractory cases. Moreover, pleurodesis may be indicated in chronic relapsing cases

Assessing Radiological Response to Immunotherapy in Lung Cancer: An Evolving Arena.

In the past decade, immune checkpoint inhibitors (ICIs) have entered the treatment landscape of non-small-cell lung cancer, signalling a paradigm shift within the field characterized by significant survival benefits for patients with advanced and metastatic disease, and especially those with non-targetable genetic oncogenic driver mutations. However, the shift towards immune-based treatments has created new challenges in oncology. Atypical immunotherapy response patterns, including pseudo-progression and hyperprogressive disease, as well as immune-related adverse events have generated the need for new methods to predict patient response to treatment. Hence, new versions of the traditional Response Evaluation Criteria for Solid Tumors (RECIST) have emerged to help characterise with better accuracy radiological findings concerning patient response classification to immunotherapy. This review discusses response evaluation criteria relevant to unique radiological findings observed in patients treated with immunotherapy for non-small-cell lung cancer

Predicting the Fission Yeast Protein Interaction Network

A systems-level understanding of biological processes and information flow requires the mapping of cellular component interactions, among which protein–protein interactions are particularly important. Fission yeast (Schizosaccharomyces pombe) is a valuable model organism for which no systematic protein-interaction data are available. We exploited gene and protein properties, global genome regulation datasets, and conservation of interactions between budding and fission yeast to predict fission yeast protein interactions in silico. We have extensively tested our method in three ways: first, by predicting with 70–80% accuracy a selected high-confidence test set; second, by recapitulating interactions between members of the well-characterized SAGA co-activator complex; and third, by verifying predicted interactions of the Cbf11 transcription factor using mass spectrometry of TAP-purified protein complexes. Given the importance of the pathway in cell physiology and human disease, we explore the predicted sub-networks centered on the Tor1/2 kinases. Moreover, we predict the histidine kinases Mak1/2/3 to be vital hubs in the fission yeast stress response network, and we suggest interactors of argonaute 1, the principal component of the siRNA-mediated gene silencing pathway, lost in budding yeast but preserved in S. pombe. Of the new high-quality interactions that were discovered after we started this work, 73% were found in our predictions. Even though any predicted interactome is imperfect, the protein network presented here can provide a valuable basis to explore biological processes and to guide wet-lab experiments in fission yeast and beyond. Our predicted protein interactions are freely available through PInt, an online resource on our website (www.bahlerlab.info/PInt)

Cell-autonomous integrin control of Wnt and Notch signalling during somitogenesis

Integrins act at signalling crossroads, and their interactions with other signal transduction pathways are key to the regulation of normal and pathological cell cytoarchitecture and behaviour. Here, we describe a signalling cascade that acts during the formation of the defining segmental features of the vertebrate body – the somites – in which β1-integrin activity regulates epithelialisation by controlling downstream Wnt and Notch activity crucial for somite border formation. Using in vivo transcriptional inhibition in the developing chick embryo, we show that β1-integrin in the anterior presomitic mesoderm activates canonical Wnt signalling in a cell-autonomous, `outside-inside' manner. Signalling is mediated by integrin-linked kinase (ILK), leading to modulation of glycogen synthase kinase 3β (GSK3β) phosphorylation, and activates Notch signalling in the anterior presomitic mesoderm. The two signalling pathways then cooperate to promote somite formation via cMESO1/Mesp2. Our results show that β1-integrin can regulate cell shape and tissue morphogenesis indirectly, by regulation of downstream signalling cascades