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

Expansion of the catalytic repertoire of alcohol dehydrogenases in plant metabolism

Medium-chain alcohol dehydrogenases (ADHs) comprise a highly conserved enzyme family that catalyse the reversible reduction of aldehydes. However, recent discoveries in plant natural product biosynthesis suggest that the catalytic repertoire of ADHs has been expanded. Here we report the crystal structure of dihydroprecondylocarpine acetate synthase (DPAS), an ADH that catalyses the non-canonical 1,4-reduction of an alpha,beta-unsaturated iminium moiety. Comparison with structures of plant-derived ADHs suggest the 1,4-iminium reduction does not require a proton relay or the presence of a catalytic zinc ion in contrast to canonical 1,2-aldehyde reducing ADHs that require the catalytic zinc and a proton relay. Furthermore, ADHs that catalysed 1,2-iminium reduction required the presence of the catalytic zinc and the loss of the proton relay. This suggests how the ADH active site can be modified to perform atypical carbonyl reductions, providing insight into how chemical reactions are diversified in plant metabolism

The new Athens center on data processing from the neutron monitor network in real time

International audienceThe ground-based neutron monitors (NMs) record galactic and solar relativistic cosmic rays which can play a useful key role in space weather forecasting, as a result of their interaction with interplanetary disturbances. The Earth's-based neutron monitor network has been used in order to produce a real-time prediction of space weather phenomena. Therefore, the Athens Neutron Monitor Data Processing Center (ANMODAP) takes advantage of this unique multi-directional device to solve problems concerning the diagnosis and forecasting of space weather. At this moment there has been a multi-sided use of neutron monitors. On the one hand, a preliminary alert for ground level enhancements (GLEs) may be provided due to relativistic solar particles and can be registered around 20 to 30 min before the arrival of the main part of lower energy particles responsible for radiation hazard. To make a more reliable prognosis of these events, real time data from channels of lower energy particles and X-ray intensity from the GOES satellite are involved in the analysis. The other possibility is to search in real time for predictors of geomagnetic storms when they occur simultaneously with Forbush effects, using hourly, on-line accessible neutron monitor data from the worldwide network and applying a special method of processing. This chance of prognosis is only being elaborated and considered here as one of the possible uses of the Neutron Monitor Network for forecasting the arrival of interplanetary disturbance to the Earth. The achievements, the processes and the future results, are discussed in this work

Renal cancer and Wegener's granulomatosis: a case report

Wegener's granulomatosis (WG) is a systemic disorder characterized by necrotizing vasculitis involving the respiratory tract, and in most cases, the kidneys. The most common manifestation of WG in the kidneys is segmental necrotizing glomerulonephritis. The presence of a renal mass as a manifestation of WG is rare. We report a patient with WG in whom a CT scan revealed an infiltrating mass in the lower portion of the left kidney. After surgical exploration, we performed an open radical nephrectomy. Histopathology showed clear cell type renal cell carcinoma (RCC). RCC associated with WG has been reported in only a few cases, and in most of them, the diseases started simultaneously, suggesting common pathogenetic pathways. Long-term immunosuppressive treatment is a known risk factor in the development of malignancies, so occurrence of RCC in WG has been proposed as a side effect of cyclophosphamide treatment. Furthermore, it is important to make a differential diagnosis between RCC and pseudotumors in WG as they cannot be distinguished solely on basis of imaging findings. Due to the higher risk of urologic malignancies, more frequent checkups and screening of WG patients should be considered

Antioxidant activity relationship of phenolic compounds in Hypericum perforatum L.

<p>Abstract</p> <p>Background</p> <p>The St John's Wort (<it>Hypericum perforatum</it>; Clusiaceae) has been used in traditional and modern medicine for a long time due to its high content of biologically active phenolics. The purpose of this work was to develop a method for their fractionation and identification, and to determine the most active antioxidant compounds in plant extract.</p> <p>Results</p> <p>An LC-MS method which enables fast qualitative and semiquantitative analysis was developed. The composition determined is in agreement with the previous results, where 6 flavonoids, 4 naphthodianthrones and 4 phloroglucinols have been identified. Significant antioxidant activity was determined for most of the fractions by DPPH assay (the lowest IC₅₀of 0.52 μg/ml), NO scavenging (6.11 μg/ml), superoxide scavenging (1.86 μg/ml), lipid peroxidation (0.0079 μg/ml) and FRAP (the highest reduction capacity of 104 mg Fe equivalents/g) assays.</p> <p>Conclusion</p> <p>LC-MS technique has been successfully applied for a quick separation and identification of the major components of <it>H. perforatum </it>fractions. Majority of the fractions analyzed have expressed a very high antioxidative activity when compared to synthetic antioxidants. The antioxidant activity could be attributed to flavonoids and phenolic acids, while phloroglucinols and naphthodianthrones showed no significant activity. It is demonstrated that it is possible to obtain, by fractionation, <it>H. perforatum </it>preparations with significantly increased phloroglucinols-to-naphthodianthrones ratio (up to 95:5).</p

Microneedle Array Design Determines the Induction of Protective Memory CD8+ T Cell Responses Induced by a Recombinant Live Malaria Vaccine in Mice

BACKGROUND: Vaccine delivery into the skin has received renewed interest due to ease of access to the immune system and microvasculature, however the stratum corneum (SC), must be breached for successful vaccination. This has been achieved by removing the SC by abrasion or scarification or by delivering the vaccine intradermally (ID) with traditional needle-and-syringes or with long microneedle devices. Microneedle patch-based transdermal vaccine studies have predominantly focused on antibody induction by inactivated or subunit vaccines. Here, our principal aim is to determine if the design of a microneedle patch affects the CD8(+) T cell responses to a malaria antigen induced by a live vaccine. METHODOLOGY AND FINDINGS: Recombinant modified vaccinia virus Ankara (MVA) expressing a malaria antigen was percutaneously administered to mice using a range of silicon microneedle patches, termed ImmuPatch, that differed in microneedle height, density, patch area and total pore volume. We demonstrate that microneedle arrays that have small total pore volumes induce a significantly greater proportion of central memory T cells that vigorously expand to secondary immunization. Microneedle-mediated vaccine priming induced significantly greater T cell immunity post-boost and equivalent protection against malaria challenge compared to ID vaccination. Notably, unlike ID administration, ImmuPatch-mediated vaccination did not induce inflammatory responses at the site of immunization or in draining lymph nodes. CONCLUSIONS/SIGNIFICANCE: This study demonstrates that the design of microneedle patches significantly influences the magnitude and memory of vaccine-induced CD8(+) T cell responses and can be optimised for the induction of desired immune responses. Furthermore, ImmuPatch-mediated delivery may be of benefit to reducing unwanted vaccine reactogenicity. In addition to the advantages of low cost and lack of pain, the development of optimised microneedle array designs for the induction of T cell responses by live vaccines aids the development of solutions to current obstacles of immunization programmes

Synergism/complementarity of recombinant adenoviral vectors and other vaccination platforms during induction of protective immunity against malaria

The lack of immunogenicity of most malaria antigens and the complex immune responses required for achieving protective immunity against this infectious disease have traditionally hampered the development of an efficient human malaria vaccine. The current boom in development of recombinant viral vectors and their use in prime-boost protocols that result in enhanced immune outcomes have increased the number of malaria vaccine candidates that access pre-clinical and clinical trials. In the frontline, adenoviruses and poxviruses seem to be giving the best immunization results in experimental animals and their mutual combination, or their combination with recombinant proteins (formulated in adjuvants and given in sequence or being given as protein/virus admixtures), has been shown to reach unprecedented levels of anti-malaria immunity that predictably will be somehow reproduced in the human setting. However, all this optimism was previously seen in the malaria vaccine development field without many real applicable results to date. We describe here the current state-of-the-art in the field of recombinant adenovirus research for malaria vaccine development, in particular referring to their use in combination with other immunogens in heterologous prime-boost protocols, while trying to simultaneously show our contributions and point of view on this subject

Prime–boost vaccination with plasmid and adenovirus gene vaccines control HER2/neu(+ )metastatic breast cancer in mice

INTRODUCTION: Once metastasis has occurred, the possibility of completely curing breast cancer is unlikely, particularly for the 30 to 40% of cancers overexpressing the gene for HER2/neu. A vaccine targeting p185, the protein product of the HER2/neu gene, could have therapeutic application by controlling the growth and metastasis of highly aggressive HER2/neu(+ )cells. The purpose of this study was to determine the effectiveness of two gene vaccines targeting HER2/neu in preventive and therapeutic tumor models. METHODS: The mouse breast cancer cell line A2L2, which expresses the gene for rat HER2/neu and hence p185, was injected into the mammary fat pad of mice as a model of solid tumor growth or was injected intravenously as a model of lung metastasis. SINCP-neu, a plasmid containing Sindbis virus genes and the gene for rat HER2/neu, and Adeno-neu, an E1,E2a-deleted adenovirus also containing the gene for rat HER2/neu, were tested as preventive and therapeutic vaccines. RESULTS: Vaccination with SINCP-neu or Adeno-neu before tumor challenge with A2L2 cells significantly inhibited the growth of the cells injected into the mammary fat or intravenously. Vaccination 2 days after tumor challenge with either vaccine was ineffective in both tumor models. However, therapeutic vaccination in a prime–boost protocol with SINCP-neu followed by Adeno-neu significantly prolonged the overall survival rate of mice injected intravenously with the tumor cells. Naive mice vaccinated using the same prime–boost protocol demonstrated a strong serum immunoglobulin G response and p185-specific cellular immunity, as shown by the results of ELISPOT (enzyme-linked immunospot) analysis for IFNγ. CONCLUSION: We report herein that vaccination of mice with a plasmid gene vaccine and an adenovirus gene vaccine, each containing the gene for HER2/neu, prevented growth of a HER2/neu-expressing breast cancer cell line injected into the mammary fat pad or intravenously. Sequential administration of the vaccines in a prime–boost protocol was therapeutically effective when tumor cells were injected intravenously before the vaccination. The vaccines induced high levels of both cellular and humoral immunity as determined by in vitro assessment. These findings indicate that clinical evaluation of these vaccines, particularly when used sequentially in a prime–boost protocol, is justified

The CPLEAR detector at CERN

The CPLEAR collaboration has constructed a detector at CERN for an extensive programme of CP-, T- and CPT-symmetry studies using ${\rm K}^0$ and $\bar{\rm K}^0$ produced by the annihilation of $\bar{\rm p}$'s in a hydrogen gas target. The ${\rm K}^0$ and $\bar{\rm K}^0$ are identified by their companion products of the annihilation ${\rm K}^{\pm} \pi^{\mp}$ which are tracked with multiwire proportional chambers, drift chambers and streamer tubes. Particle identification is carried out with a liquid Cherenkov detector for fast separation of pions and kaons and with scintillators which allow the measurement of time of flight and energy loss. Photons are measured with a lead/gas sampling electromagnetic calorimeter. The required antiproton annihilation modes are selected by fast online processors using the tracking chamber and particle identification information. All the detectors are mounted in a 0.44 T uniform field of an axial solenoid of diameter 2 m and length 3.6 m to form a magnetic spectrometer capable of full on-line reconstruction and selection of events. The design, operating parameters and performance of the sub-detectors are described.

DNA vaccination for prostate cancer: key concepts and considerations

While locally confined prostate cancer is associated with a low five year mortality rate, advanced or metastatic disease remains a major challenge for healthcare professionals to treat and is usually terminal. As such, there is a need for the development of new, efficacious therapies for prostate cancer. Immunotherapy represents a promising approach where the host’s immune system is harnessed to mount an anti-tumour effect, and the licensing of the first prostate cancer specific immunotherapy in 2010 has opened the door for other immunotherapies to gain regulatory approval. Among these strategies DNA vaccines are an attractive option in terms of their ability to elicit a highly specific, potent and wide-sweeping immune response. Several DNA vaccines have been tested for prostate cancer and while they have demonstrated a good safety profile they have faced problems with low efficacy and immunogenicity compared to other immunotherapeutic approaches. This review focuses on the positive aspects of DNA vaccines for prostate cancer that have been assessed in preclinical and clinical trials thus far and examines the key considerations that must be employed to improve the efficacy and immunogenicity of these vaccines