Global-Local Finite Element Analysis

114 σ.Η αναλυτική επίλυση πολύπλοκων προβλημάτων της μηχανικής στις μέρες μας καθίσταται δυσχερής εως αδύνατη χωρίς την εφαρμογή αριθμητικών μεθόδων και τη χρήση ηλεκτρονικού υπολογιστή. Η μέθοδος των πεπερασμένων στοιχείων αποτελεί σήμερα ένα ισχυρό εργαλείο για την επίλυση τέτοιων προβλημάτων και εξελίσσεται με μεγάλη ταχύτητα τόσο σε ακαδημαϊκό όσο και σε επαγγελματικό επίπεδο. Ενδεικτικά, αν και επινοήθηκε και χρησιμοποιήθηκε για τη στατική ανάλυση φορέων, έχει καθολικότερη εφαρμογή σε μια ευρύτερη κατηγορία προβλημάτων του μηχανικού, όπως στη ρευστομηχανική, στη μεταφορά θερμότητας, στην ακουστική, στον ηλεκτρομαγνητισμό και στην εμβιομηχανική. Επιπλέον, η εξέλιξη στων Η/Υ με τις ολοένα μεγαλύτερες δυνατότητες διαχείρισης όγκου δεδομένων αλλά και με την αύξηση της ταχύτητας εκτέλεσης των αριθμητικών πράξεων κατέστησε εφικτή την επίλυση σύνθετων προβλημάτων τα οποία θεωρούνταν απροσπέλαστα πριν μερικά χρόνια. Στην κατηγορία αυτή, των προβλημάτων αυξημένου υπολογιστικού κόστους, ανήκει και η καταστατική περιγραφή πολυφασικών υλικών. Είναι γεγονός ότι το μεγαλύτερο μέρος των παραγώμενων δομικών υλικών σήμερα, παρουσιάζει κάποιο είδος ανομοιογένειας, διακριτή ή μη στην κλίμακα δομικών έργων. Χαρακτηριστικά παραδείγματα αποτελούν τα κράματα μετάλλων, τα πορώδη, τα πολυκρυσταλλικά και τα σύνθετα υλικά στα οποία το μέγεθος, το σχήμα και οι ιδιότητες των συστατικών τους μερών καθορίζουν άμεσα τη συνολική τους μηχανική συμπεριφορά. Διάφορες τεχνικές έχουν αναπτυχθεί για την προσομοίωση και την περιγραφή της απόκρισης ανομοιογενών υλικών. Η παρούσα εργασία επικεντρώνεται στη μέθοδο ομογενοποίησης πολλαπλών κλιμάκων η οποία συνίσταται στην επίλυση δύο εμφωλευμένων προβλημάτων συνοριακών τιμών, για τη μακροκλίμακα και τη μικροκλίμακα αντίστοιχα. Τα βασικά χαρακτηριστικά μιας τέτοιας μεθόδου είναι ότι - Δεν απαιτείται η περιγραφή των καταστατικών νόμων του μακροφορέα. - Παρέχει τη δυνατότητα ενσωμάτωσης μεγάλων παραμορφώσεων και στροφών τόσο στην προσομοίωση της μικροκλίμακας όσο και του μακροφορέα. - Παρέχει τη δυνατότητα λεπτομερούς προσομοίωσης των συστατικών μερών της μικροκλίμακας. - Επιτρέπει οποιαδήποτε τεχνική επίλυσης στην κλίμακα του μικροφορέα. Αναλυτικά, σύμφωνα με τη μέθοδο αυτή. υπολογίζεται το διάνυσμα ανηγμένων παραμορφώσεων σε κάθε υλικό σημείο του μακροφορέα το οποίο στη συνέχεια χρησιμοποιείται για τη μόρφωση των συνοριακών συνθηκών του αντιπροσωπευτικού μικροφορέα στο αντίστοιχο σημείο. Μετά την επίλυση του προβλήματος συνοριακών τιμών της μικροκλίμακας, το διάνυσμα των τάσεων του μακροφορέα υπολογίζεται μέσα από τη διαδικασία ομογενοποίησης του πεδίου των τάσεων και κατά τον τρόπο αυτό υπολογίζεται η σχέση τάσεων ανηγμένων παραμορφώσεων για κάθε υλικό σημείο Ωστόσο, υπάρχουν κάποιοι περιορισμοί στην εφαρμογή της εν λόγω υπολογιστικής τεχνικής. Συγκεκριμένα, παρά το ότι κατά την προσομοίωση λαμβάνονται υπ' όψην οι διάφορες παράμετροι της μικροκλίμακας όπως το ποσοστό όγκου, η κατανομή και η μορφολογία των συστατικών μερών του υλικού, τα αποτελέσματα της μεθόδου είναι ανεξάρτητα από το απόλυτο μέγεθος του αντιπροσωπευτικού όγκου της μικροκλίμακας. Παρ' όλα αυτά, η τεχνική ομογενοποίησης στα πλαίσια ανάλυσης πολλαπλών κλιμάκων αποτελεί ένα σημαντικό εργαλείο για τον υπολογισμό των καταστατικών σχέσεων πολυφασικών υλικών στα οποία είναι αδύνατη η εφαρμογή οποιασδήποτε άλλης μεθόδου.Nowadays, analysis of complicated problems in the domain of mechanics consti- tutes a hard and even impossible task without the implementation of numerical methods and the employment of computational machines. Finite element method is a powerful tool for the solution of such problems and is rapidly developed in an academic and professional sense. Even if it was developed and implemented for structural analysis, it is widely employed in several domains such as in fluid mechanics, heat transfer, acoustics and electromagnetism. Furthermore, the development of computer hardware in terms of data processing, has significantly contributed to the solution of problems that were considered inaccessible a few years ago. Most of the materials produced in industry are heterogeneous on one or another spatial scale. Typical examples include metal alloy systems, porous media and polycrystalline materials and composites. The overall response of these micro heterogeneous materials depends strongly on the size, shape properties and spatial distribution of the microstructural components. Several techniques have been developed for the prediction of the macroscopic behavior of such materials. The present work is concentrated on the first order homogenization technique in the framework of a multi-scale approach which consists of the solution of two nested boundary value problems, for the macro-scale and the micro-scale respectively. Methods of this type - Do not require any constitutive assumption with respect to the overall ma- terial behavior. - Enable the incorporation of large deformations and rotations on both micro and macrolevel. - Provide the possibility to introduce detailed microstructural information. - Allow the use of any modelling technique at the microlevel. Concretely, according to this approach, the macroscopic deformation tensor is calculated for every integration point of the macrostructure and then is used to formulate the kinematic boundary conditions for the associated microstructural representative volume element (RVE). After the solution of the microstructural boundary value problem, the macroscopic stress tensor is computed by averaging the resulting microstructural stress field over the volume of the RVE and as a result, we obtain the stress-strain relation at every macroscopic point. However, there is a major disadvantage of the existing first-order computational homogenization. More specifically, this technique can account for the volume fraction, distribution and morphology of the micro-components however, it cannot take into account the absolute size of the microstructure making it thus impossible to treat microstructural size effects. Nevertheless, computational homogenization provides a significant strategy to obtain micro-macro structure-property relations for materials for which the overall macroscopic response cannot be computed by any other method.Κωνσταντινος Ε. Τατση

Risk for Infection with Highly Pathogenic Influenza A Virus (H5N1) in Chickens, Hong Kong, 2002

Infection was spread to commercial poultry farms through retail marking of live birds

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Results (F ratios/<i>p</i>-values) of two-way ANOVAs comparing relative sensitivities of durations of epidemics produced by versions of the model assuming epidemics were initiated via recrudescence or via immigration.

<p>Results (F ratios/<i>p</i>-values) of two-way ANOVAs comparing relative sensitivities of durations of epidemics produced by versions of the model assuming epidemics were initiated via recrudescence or via immigration.</p

Experimental design for the sensitivity analysis and robustness analysis.

<p>Three Monte Carlo simulations were run for each parameter combination.</p

Simulated differences in the magnitudes of epidemics (maximum proportion of I individuals in the population) and durations of epidemics (number of days with proportion of I>0.10) resulting from changes in the values of important model parameters in versions of the model assuming epidemics were initiated (A) via recrudescence and (B) via immigration (Error bars represent ± SE).

<p>Simulated differences in the magnitudes of epidemics (maximum proportion of I individuals in the population) and durations of epidemics (number of days with proportion of I>0.10) resulting from changes in the values of important model parameters in versions of the model assuming epidemics were initiated (A) via recrudescence and (B) via immigration (Error bars represent ± SE).</p

Results (F ratios/<i>p</i>-values) of two-way ANOVAs comparing relative sensitivities of magnitudes of epidemics produced by versions of the model assuming epidemics were initiated via recrudescence or via immigration.

<p>Results (F ratios/<i>p</i>-values) of two-way ANOVAs comparing relative sensitivities of magnitudes of epidemics produced by versions of the model assuming epidemics were initiated via recrudescence or via immigration.</p

Conceptual model of the possible role of recrudescence in the persistence of Hendra virus in isolated flying-fox populations representing the daily dynamics of a colony consisting of (A) the various life history stages (pups, P; juveniles, J; pre-reproductive sub-adults, SA; reproductively mature adults, A), and (B) the various disease stages (maternally immune young-of-the-year, Mi; susceptible, S; exposed and latently infected, E; infectious, I; and recovered, R) individuals.

<p>Conceptual model of the possible role of recrudescence in the persistence of Hendra virus in isolated flying-fox populations representing the daily dynamics of a colony consisting of (A) the various life history stages (pups, P; juveniles, J; pre-reproductive sub-adults, SA; reproductively mature adults, A), and (B) the various disease stages (maternally immune young-of-the-year, Mi; susceptible, S; exposed and latently infected, E; infectious, I; and recovered, R) individuals.</p