Streptococcus suis (S. suis) is a common swine pathogen but also poses a threat to human health in causing meningitis and severe cases of streptococcal toxic shock-like syndrome (STSLS). Therefore, it is crucial to understand how S. suis interacts with the host immune system during bacteremia. As S. suis has the ability to introduce d-alanine into its lipoteichoic acids (LTAs), we investigated the working hypothesis that cell wall modification by LTA d-alanylation influences the interaction of S. suis with porcine blood immune cells. We created an isogenic mutant of S. suis strain 10 by in-frame deletion of the d-alanine d-alanyl carrier ligase (DltA). d-alanylation of LTAs was associated with reduced phagocytosis of S. suis by porcine granulocytes, reduced deposition of complement factor C3 on the bacterial surface, increased hydrophobicity of streptococci, and increased resistance to cationic antimicrobial peptides (CAMPs). At the same time, survival of S. suis was not significantly increased by LTA d-alanylation in whole blood of conventional piglets with specific IgG. However, we found a distinct cytokine pattern as IL-1β but not tumor necrosis factor (TNF)-α levels were significantly reduced in blood infected with the ΔdltA mutant. In contrast to TNF-α, activation and secretion of IL-1β are inflammasome-dependent, suggesting a possible influence of LTA d-alanylation on inflammasome regulation. Especially in the absence of specific antibodies, the association of S. suis with porcine monocytes was reduced by d-alanylation of its LTAs. This dltA-dependent phenotype was also observed with a non-encapsulated dltA double mutant indicating that it is independent of capsular polysaccharides. High antibody levels caused high levels of S. suis—monocyte—association followed by inflammatory cell death and strong production of both IL-1β and TNF-α, while the influence of LTA d-alanylation of the streptococci became less visible. In summary, the results of this study expand previous findings on d-alanylation of LTAs in S. suis and suggest that this pathogen specifically modulates association with blood leukocytes through this modification of its surface.

Gamma-ray bursts (GRBs) are the most energetic electromagnetic events in the universe, but there are still unanswered questions about them, like the underlying radiation mechanisms that cause the different parts of their light curves. Given that Wolf-Rayet (WR) stars with circumburst rings could be the progenitor of GRBs with late flares \cite{complex}, the purpose of this thesis was to determine if the precursor and the main emission of GRBs with late time flares might originate due to different radiation mechanisms, and thereby if WR stars could be the progenitors. 271 of the longest GRBs with flux above 10 photons/cm$^2$/s were studied and all GRBs with a precursor and a defined quiescent period were chosen for further studies. The chosen 39 GRBs were divided into different categories depending on the appearance of their light curves. A gold sample with $R_{P, max}/R_{D, max} < 0.4$ and $T_Q/T_{tot} > 0.5$, for the maximum count rate of the precursor $R_{P, max}$, the dominant emission $R_{D, max}$, and for the normalised quiescent period $T_Q/T_{tot}$ was concluded to have similar characteristics and to fit what would be expected if WR stars would be the progenitors. This group of GRBs all have a short and less bright precursor, a long quiescent period and a main emission which is brighter and longer than the precursor. The distributions of the photon index $\alpha$ for the precursor and the dominant emission for the gold sample indicate that the precursor is due to photospheric emission and the dominant emission is due to synchrotron emission. This is consistent with the interpretation that the precursor is a result of the jet interacting with the photosphere and the dominant emission is a result of interactions with the circumburst ring of a star like the WR stars. The next step in this investigation would be to study GRBs with more than one precursor that otherwise fit the description of the gold sample, to determine if these fit into the gold sample as well. / Gammablixtrar (GRB) är de mest kraftfulla elektromagnetiska eventen i universum men det finns fortfarande obesvarade frågor om dem, som de underliggande strålningsmekanismerna som orsakar de olika delarna av deras ljuskurvor. För en del av alla GRBs tar det upp till eller mer än 100 sekunder från utlösningstiden till det att en topp ses i ljuskurvan. För dessa finns då ofta en liten svag topp, som följs av en lång lugn period och sedan den dominant, starkare utstrålningen. GRBs tros kunna härstamma från Wolf-Rayet-stjärnor (WR-stjärnor), som är massiva, döende stjärnor som kan vara omringade av bubblor, nebulosor, och ringar. Om GRBs härstammar från dessa förväntas den första mindre toppen och den andra större toppen uppkomma på grund av olika strålningsprocesser. Syftet med detta projekt var därför att undersöka huruvida dessa toppar uppkommer på grund av olika processer eller ej. Sammanfattningsvis så hittades en distinkt och homogen grupp av GRBs med likande egenskaper. Resultaten påvisar att den första svaga toppen är fotosfärisk strålning, så att den uppkommer på grund av att jetstrålen från GRBn interagerar med fotosfären. Därtill tyder resultaten på att den dominanta starkare toppen är synkrotronstrålning, som kan uppkomma när jetstrålen interagerar med en ring runt en WR-stjärna. Nästa steg i detta projekt skulle vara att studera GRBs med fler än en mindre topp innan den dominant utstrålningen, för att se om dessa också har liknande egenskaper som de som hittades i den homogena gruppen.

Besides being sources of gravitational waves, there has been evidence that neutron starmergers release neutron-rich material suitable for the production of heavy r-process nuclei.The radioactive decay of these freshly synthesised elements powers a rapidly evolvingthermal transient, the “macronova” (also known as “kilonova”). Its spectral propertiesstrongly depend on the ejecta composition, since neutron rich material synthesises heavyr-process elements that can efficiently trap radiation inside the ejecta producing a longlasting signal peaking in the red part of the spectrum. The first detection of a binaryneutron star merger was also accompanied by the evidence of a relativistic jet. Despitebeing ascertained the presence of these two dynamical components, neutron-rich ejectaand ultra-relativistic jet, the observational consequences of the interplay between the twois still unclear. In the paper we investigate such interaction through dedicated specialrelativistic hydrodynamic simulations, starting from a realistic environment obtained byprevious works. Light curves are then constructed up to the time scale of days by postprocessing the hydrodynamic results adopting proper radiative transfer. I show thatjet propagation within such environment can significantly affect the observation of theradioactive transient. A relativistic outflow can in fact “punch-away” a fraction of highopacity material before the brightening of the macronova, resulting in the transient beingbrighter and bluer for on-axis observers in the first few days. In this way the jet impactsboth time scale and luminosity of the macronova peak, that are the two main observablesallowing the estimate of the ejecta properties.

Behavioral fever is an essential coping mechanism across ectothermic phyla to aid in combating pathogenic threats. Ectotherms lack internal temperature regulation associated with fever in endotherms; thus, ectotherms can exhibit a behavioral fever response when immunocompromised to thermoregulate by moving to warmer locations. The salamander order Caudata, tend to be keystone species in their resident ecosystems through their role as secondary consumers of invertebrates to maintain the food chain. With growing interest about ecology and conservation of salamanders as species diversity declines, this study was designed to determine if salamanders use their environment to take advantage of behavioral fever. The lungless salamander, Plethodon glutinosus, was used to investigate behavioral fever through exposure to the synthetic viral pyrogen polyinosinic:polycytidylic acid (Poly (I:C)) at doses of 15 µg/g by live wet weight. After 24 hours, the induced fever specimens were placed in a linear temperature gradient with a controlled humidity of 95% throughout. Average temperature preferences were then monitored over a 12-hour period and resulted in control animals preferring cold and moderate temperatures between 15-19 °C while all poly (I:C) injected animals preferred higher temperatures from 19-21°C (p<<0.0001). This result supports that P. glutinous responds to immunocompromising threats such as presented by synthetic viral pyrogen Poly (I:C) through use of behavioral fever.

Τα οπτικά δίκτυα αποτελούν την αποδοτικότερη επιλογή όσον αφορά την εγκατάσταση ευρυζωνικών δικτύων κορμού, καθώς παρουσιάζουν μοναδικά χαρακτηριστικά μετάδοσης. Διαθέτουν τεράστιο εύρος ζώνης, υψηλή αξιοπιστία, ενώ επίσης έχουν μειωμένο κόστος μετάδοσης ανά bit πληροφορίας σε σχέση με τα υπόλοιπα ενσύρματα δίκτυα. Σημαντικές ερευνητικές προσπάθειες έχουν επικεντρωθεί στις προοπτικές μετάβασης από τα παραδοσιακά στατικά δίκτυα κυκλωμάτων, στα οποία χρησιμοποιείται από-σημείο-σε-σημείο οπτική μετάδοση, σε δίκτυα μετάδοσης δεδομένων που προσφέρουν δυναμική και γρήγορη επαναρύθμιση των οπτικών μονοπατιών και πρόσβαση σε χωρητικότητες κάτω του ενός μήκους κύματος, ανάλογα με τις απαιτήσεις των χρηστών και των εκάστοτε εφαρμογών. Τα τελευταία χρόνια υπάρχει η τάση για δημιουργία δυναμικών και επαναρυθμιζόμενων οπτικών δικτύων μεταγωγής κυκλώματος (Optical Circuit Switching), τα οποία θα βασίζονται σε διαφανείς κόμβους μεταγωγής. Η μονάδα μεταγωγής των δικτύων οπτικής μεταγωγής κυκλώματος είναι τα οπτικά μονοπάτια (lightpaths) και το βασικό πρόβλημα βελτιστοποίησης που σχετίζεται με την αποδοτική εκμετάλλευση της χωρητικότητας τέτοιων δικτύων είναι το πρόβλημα της δρομολόγησης και ανάθεσης μήκους κύματος (Routing and Wavelength Assignment - RWA). Στα αμιγώς διαφανή (transparent) οπτικά δίκτυα κυκλώματος η μετάδοση του σήματος υποβαθμίζεται από μια σειρά φυσικών εξασθενήσεων (physical impairments), σε σημείο που η εγκατάσταση ενός οπτικού μονοπατιού να μην είναι αποδεκτή. Για την αντιμετώπιση αυτού του προβλήματος στην παρούσα διατριβή προτείνουμε αλγόριθμους οι οποίοι λαμβάνουν υπόψη τους τις φυσικές εξασθενήσεις (Impairment Aware RWA ή ΙΑ-RWA algorithms) τόσο για στατική όσο και για δυναμική κίνηση. Συγκεκριμένα, παρουσιάζουμε έναν IA-RWA αλγόριθμο για στατική κίνηση, ο οποίος βασίζεται στην τεχνική της LP-χαλάρωσης και χρησιμοποιεί αποδοτικές μεθόδους για την παραγωγή ακεραίων λύσεων. Εκφράζουμε τις φυσικές εξασθενήσεις μέσω επιπλέον περιορισμών στην LP μοντελοποίηση του RWA προβλήματος, επιτυγχάνοντας την διαστρωματική βελτιστοποίηση (cross-layer optimization) πάνω στο φυσικό επίπεδο και στο επίπεδο δικτύου. Στη συνέχεια, προτείνουμε έναν IA-RWA αλγόριθμο πολλαπλών κριτηρίων (multi-cost) για δυναμική κίνηση. Ορίζουμε ένα διάνυσμα από κόστη για κάθε σύνδεσμο και τις πράξεις συσχέτισης αυτών, ώστε να μπορούμε να υπολογίσουμε το διάνυσμα από κόστη ενός μονοπατιού και μέσω αυτού να αξιολογήσουμε την ποιότητα μετάδοσης των διαθέσιμων μηκών κύματος του μονοπατιού. Για την εξυπηρέτηση μιας νέας αίτησης σύνδεσης, ο αλγόριθμος πολλαπλών κριτηρίων υπολογίζει το σύνολο των μη κυριαρχούμενων μονοπατιών, από την πηγή στο ζητούμενο προορισμό, και μετά εφαρμόζει μια πολιτική για να επιλέξει το βέλτιστο οπτικό μονοπάτι. Προτείνουμε και αξιολογούμε την απόδοση μιας σειράς από πολιτικές επιλογής, η κάθε μια από τις οποίες ουσιαστικά αντιστοιχεί σε έναν διαφορετικό δυναμικό IA-RWA αλγόριθμο. Στη συνέχεια, στρέφουμε την προσοχή μας στα δίκτυα οπτικής μεταγωγής καταιγισμών (Optical Burst Switching – OBS), τα οποία θεωρούνται ότι αποτελούν το επόμενο στάδιο των δικτύων οπτικής μεταγωγής κυκλώματος, όπου η δέσμευση της χωρητικότητας γίνεται για μικρότερο χρονικό διάστημα. Στα OBS δίκτυα, τα πακέτα που έχουν τον ίδιο προορισμό και παρόμοιες απαιτήσεις ποιότητας υπηρεσίας συναθροίζονται σε καταιγισμούς (bursts). Οι καταιγισμοί μεταδίδονται πάνω από αμιγώς οπτικά μονοπάτια, τα οποία ρυθμίζονται με τη χρήση πακέτων ελέγχου που μεταδίδονται πριν από τους αντίστοιχους καταιγισμούς και τα οποία επεξεργάζονται ηλεκτρονικά οι ενδιάμεσοι κόμβοι. Επικεντρώνουμε την προσοχή μας σε δυο βασικά στοιχεία ενός δικτύου οπτικής μεταγωγής καταιγισμών, την διαδικασία συναρμολόγησης καταιγισμών και τα πρωτόκολλα σηματοδοσίας, και παραθέτουμε δύο προτάσεις για την αποδοτική ανάθεσης χωρητικότητας σε αυτά τα δίκτυα. Συγκεκριμένα, προτείνουμε και αξιολογούμε ένα νέο αλγόριθμο συναρμολόγησης καταιγισμών που βασίζεται στη μέση καθυστέρηση των πακέτων που αποτελούν έναν καταιγισμό. Δείχνουμε ότι ο προτεινόμενος αλγόριθμος συναρμολόγησης καταιγισμών μειώνει την διασπορά της καθυστέρησης των πακέτων (packet delay jitter), η οποία είναι σημαντική για μια σειρά από εφαρμογές. Στην συνέχεια προτείνουμε ένα νέο αμφίδρομο (two-way) πρωτόκολλο σηματοδοσίας που βασίζεται στις μελλοντικές (in-advance) και χαλαρωμένες χρονικά (relaxed timed) δεσμεύσεις χωρητικότητας. Στο προτεινόμενο πρωτόκολλο, κατά τη φάση εγκατάστασης της σύνδεσης οι δεσμεύσεις χωρητικότητας γίνονται για χρονικό διάστημα μεγαλύτερο από το χρόνο μετάδοσης του καταιγισμού, ώστε να αυξηθεί η πιθανότητα επιτυχούς εγκατάστασης στους επόμενους συνδέσμους του μονοπατιού. Συγκρίνουμε το προτεινόμενο πρωτόκολλο με τυπικά πρωτόκολλα που έχουν προταθεί στη βιβλιογραφία και δείχνουμε οτι μπορεί να χρησιμοποιηθεί για την παροχή διαφοροποιημένης ποιότητα υπηρεσιών (QoS differentiation) στους χρήστες του OBS δικτύου. Στη συνέχεια, εξετάζουμε το πρόβλημα της δρομολόγησης και του χρονοπρογραμματισμού συνδέσεων με χαλαρό - μη συγκεκριμένο χρόνο εκκίνησης, πρόβλημα που εμφανίζεται υπό ελαφρώς διαφορετική μορφή σε δίκτυα οπτικής μεταγωγής κυκλώματος, οπτικής μεταγωγής καταιγισμών αλλά και μεταγωγής πακέτου. Η εξυπηρέτηση αυτών των συνδέσεων γίνεται μέσω μελλοντικών δεσμεύσεων χωρητικότητας, τρόπος ο οποίος είναι τυπικός για να παρεχθεί εγγυημένη ποιότητα υπηρεσίας (QoS) στους χρήστες ενός δικτύου. Θεωρούμε ότι μας δίνεται μια σύνδεση με γνωστή πηγή και προορισμό, γνωστό ή άγνωστο όγκο δεδομένων και γνωστό ρυθμό μετάδοσης και ζητείται να αποφασίσουμε το μονοπάτι που θα ακολουθήσουν τα δεδομένα και το χρόνο που θα αρχίσει η μετάδοση. Διακριτοποιούμε το χρόνο και χρησιμοποιούμε κατάλληλα διανύσματα ως δομές δεδομένων για να αναπαραστήσουμε τη διαθεσιμότητα των συνδέσμων του δικτύου ως συνάρτηση του χρόνου. Χρησιμοποιούμε αυτά τα διανύσματα σε ένα αλγόριθμο πολλαπλών κριτηρίων για τη δρομολόγηση και το χρονοπρογραμματισμό των συνδέσεων. Αρχικά, παρουσιάζουμε έναν αλγόριθμο πολλαπλών κριτηρίων μη πολυωνυμικής πολυπλοκότητας, ο οποίος βασίζεται στην έννοια των μη-κυριαρχούμενων μονοπατιών. Μετά προτείνουμε δύο ευριστικούς αλγορίθμους πολυωνυμικής πολυπλοκότητας, ορίζοντας κατάλληλες σχέσεις ψευδο-κυριαρχίας οι οποίες μειώνουν το χώρο των λύσεων. Επίσης, προτείνουμε ένα μηχανισμό branch-and-bound, ο οποίος μπορεί να μειώσει το χώρο λύσεων στην περίπτωση που χρησιμοποιούμε μια συγκεκριμένη συνάρτηση βελτιστοποίησης για όλες τις συνδέσεις. Η απόδοση των προτεινόμενων αλγορίθμων αξιολογήθηκε σε ένα δίκτυο οπτικής μεταγωγής καταιγισμών, ωστόσο τα συμπεράσματα και η εφαρμοσιμότητα του προτεινόμενου αλγόριθμου επεκτείνεται και σε άλλου είδους οπτικά δίκτυα. Τέλος, εξετάζουμε το πρόβλημα του συνδυασμένου χρονοπρογραμματισμού των δικτυακών και υπολογιστικών πόρων που απαιτούνται για την εκτέλεση μιας διεργασίας σε ένα Δίκτυο Πλέγματος (Grid Network). Τα Δίκτυα Πλέγματος θεωρούνται το επόμενο βήμα στον τομέα των κατανεμημένων συστημάτων, εισάγοντας την έννοια της “κοινής” χρήσης γεωγραφικά κατανεμημένων και ετερογενών πόρων (υπολογιστικών, αποθηκευτικών, δικτυακών, κλπ.). Υποθέτουμε ότι η εκτέλεση μιας διεργασίας αποτελείται από δύο διαδοχικά στάδια: (α) Τη μεταφορά των δεδομένων εισόδου της διεργασίας από μια αποθηκευτική μονάδα σε μια συστοιχία υπολογιστών (cluster), (β) την εκτέλεση της διεργασίας στη συστοιχία υπολογιστών. Επεκτείνουμε τον αλγόριθμο πολλαπλών κριτηρίων για τη δρομολόγηση και το χρονοπρογραμματισμό συνδέσεων που περιγράφηκε προηγουμένως, έτσι ώστε να χειρίζεται με ένα συνδυασμένο τρόπο δικτυακούς και υπολογιστικούς πόρους για την εκτέλεση των διεργασιών. Ο προτεινόμενος αλγόριθμος επιστρέφει: (i) τη συστοιχία υπολογιστών όπου θα εκτελεστεί η διεργασία, (ii) το μονοπάτι το οποίο θα ακολουθήσουν τα δεδομένα εισόδου, (iii) τη χρονική στιγμή εκκίνησης μετάδοσης και (iv) τη χρονική στιγμή εκκίνησης εκτέλεσης της διεργασίας στη συστοιχία υπολογιστών. Ξεκινάμε παρουσιάζοντας έναν αλγόριθμο μη πολυωνυμικού χρόνου και μετά, αφού μειώσουμε κατάλληλα το χώρο λύσεων, δίνουμε έναν ευριστικό αλγόριθμο πολυωνυμικής πολυπλοκότητας. / Optical networks have developed rapidly over the last ten years and are widely used in core networks due to their superior transmission characteristics. Optical networks provide huge available capacity that can be efficiently utilized using wavelength division multiplexing (WDM) and high reliability at the lowest cost per bit ratio when compared to the other wired and wireless networking solutions. Much research has focused on ways to evolve from the typical point-to-point opaque WDM networks that are currently employed in the core to optical networks that are dynamically and quickly reconfigurable and can provide on-demand services to users at subwavelength granularity according to users’ requirements. The most common architecture utilized for establishing communication in WDM optical networks is wavelength routing that fall in the general category of Optical Circuit Switched (OCS) networks. The switched entities in OCS networks are the lightpaths and the basic optimization problem that is related to the efficient allocation of bandwidth is the routing and wavelength assignment problem (RWA). The current optical technology employed in core networks is point-to-point transmission, where the signal is regenerated at every intermediate node via optical-electronic-optical (OEO) conversion. During the recent few years, the trend clearly shows an evolution towards low-cost and high capacity all-optical transparent networks that do not utilize OEO. In transparent OCS networks the signal of a lightpath remains in the optical domain and its quality deteriorates due to a series of physical layer impairments (PLIs). These PLIs may degrade the received signal quality to the extent that the bit-error rate (BER) at the receiver may be so high that signal detection may be infeasible for some lightpaths. To address this problem we proposed algorithms that take into account the PLIs, usually referred in the literature as Impairment Aware RWA or ΙΑ-RWA algorithms, for both offline (static) and online (dynamic) traffic. In particular we propose an IA-RWA algorithm for static traffic that is based on an LP-relaxation formulation and use various efficient methods to obtain integer solutions. The physical layer impairments are included as additional constraint in the LP formulation of the RWA problem, yielding a cross-layer optimization solution between the network and the physical layers. We then proceed and propose a multi-cost IA-RWA algorithm for dynamic traffic. We define a cost vector per link and associative operators to combine these vectors so as to calculate the cost vector of a path. The parameters of these cost vectors are chosen so as to enable the quick and efficient calculation of the quality of transmission of candidate lightpaths. To serve a connection request, the proposed multi-cost algorithm calculates the set of so called non-dominated paths from the given source to the given destination, and then applies an optimization policy to choose the optimal lightpath. We propose and evaluate various optimization policies that correspond to different online IA-RWA algorithms. We then turn our attention to Optical Burst Switched (OBS) networks, which are regarded as the next step from the OCS paradigm towards a more dynamic core network that can provide on demand subwavelength services to users. In OBS networks, the packets that have the same destination and similar quality of service requirements are aggregated into bursts at the ingress nodes. When a burst is aggregated, a control packet is transmitted and is electronically processed at intermediate nodes so as to configure them for the burst that will pass transparently afterwards. We focus on two key elements of an OBS network, and in particular the burst aggregation (or burstification) process and the signaling protocol, and we propose two solutions for the efficient allocation of bandwidth in OBS networks. We propose and evaluate a novel burst assembly algorithm that is based on the average delay of the packets that comprise a burst. We show that the proposed algorithm decreases the packet delay jitter among the packets, which is important for a number of applications, including real-time, video and audio streaming, and TCP applications. Next we propose a two-way reservation signaling protocol that utilizes in-advance and relaxed timed reservation of the bandwidth. In the connection establishment phase of the proposed protocol, bandwidth reservations can exceed the duration of burst transmission (thus, relaxing the timed reservations), so as to increase the acceptance probability for the rest of the path. By controlling the degree of the relaxed timed reservations the protocol can also provide service differentiation to the users. Next we examine the problem of routing and scheduling of connections with flexible starting time in networks that support advance reservations. This problem can arise in slightly different settings in Optical Circuit Switched, Optical Burst Switched, and Optical Packet Switched networks. Such connection requests are served through advanced reservations, a process which is used to provide quality of service to users. We assume that for a connection request we are given the source, the destination, and the size of the data to be transferred with a given rate, and we are asked to provide the path and the time that the transmission should start so as to optimize a certain performance metric. We discretize the time and we use appropriate data structures (in the form of vectors) to map the utilization of the links as a function of time. We use these vectors as cost parameters in a multi-cost algorithm. We initially present a multicost algorithm of non-polynomial complexity that uses a full domination relation between paths. We then propose two mechanisms to prune the solution space in order to obtain polynomial complexity algorithms. In the first mechanism we define pseudo-domination relations that are weaker than the full domination relation. We also propose a branch-and-bound extension to the optimum algorithm that can be used for a given specific optimization function. The performance of the multicost algorithm and its variations are evaluated in an OBS network, but this does not limit the applicability of the algorithm and the conclusions can be extended in the other optical networking paradigms. Finally, we examine the problem of joint reservation of communication and computation resources that are required by a task in a Grid Network. Grid Networks are considered as the next step in distributed systems, introducing the concept of shared usage of geographically distributed and heterogeneous resources (computation, storage, communication, etc.). We assume that the task execution consists of two phases: (a) the transfer of the input data from a data storage resource, or the scheduler to a computation resource (cluster), (b) the execution of a program at the cluster. We extend the multicost algorithm for the routing and scheduling of connections, outlined above, so as to handle the reservation of computation resources as its last leg. In this way the proposed algorithm performs a joint optimization for the communication and computation part required by a task and returns: (i) the cluster to the execute the task, (ii) the path to route the input data, (iii) the time to start the transmission of data, and (iv) the time to start the execution of the task. We start by presenting an algorithm of non-polynomial complexity and then by appropriately pruning the solution space, we give a heuristic algorithm of polynomial complexity. We show that in a Grid network where the tasks are cpu- and data-intensive important performance benefits can be obtained by jointly optimizing the use of the communication and computation resources.

Résumé : Le sepsis sévère et le choc septique réfractaire sont d’incidences grandissantes dans la population et restent actuellement un défi de taille avec une mortalité variant de 30 à 70 % à 28 jours malgré l’amélioration du traitement de support. Les corticostéroïdes (CS) sont un traitement d’appoint controversé dans le sepsis sévère et le choc septique réfractaire. Ils modulent entre autre les fonctions des neutrophiles ou polymorphonuclear neutrophils cells (PMN) qui sont des acteurs de 1ère ligne dans la défense immédiate contre le sepsis et les défaillances organiques associées. Résultats : Le sepsis a pour effet de diminuer l’activité phagocytaire, ainsi que la production de radicaux libres oxygénés (ROS) des PMN au jour 1 (J1) et jour 3 (J3). Il augmente l’adhésion qui s’intensifie avec la sévérité de la maladie et persiste jusqu’à J3. Au niveau de la dégranulation, le sepsis augmente la production et la libération de la pentraxine 3 (PTX3). Le sepsis affecte le profil phénotypique des PMN en augmentant l’expression de CD66b et ST2 à J1 et J3. Il accentue également l’expression de CD64. Dans le groupe 2 (G2), ce niveau d’expression diminue à J3. Aucun effet significatif sur le chimiotactisme n’a été observé à J1, ni J3. L’usage de CS in vitro retarde l’apoptose à J1 et J3 dans le groupe 1 (G1), mais ne démontre aucune amélioration significative des fonctions des PMN ou au niveau de leur profil phénotypique. Conclusion : Le sepsis entraîne une immunoparalysie des PMN au niveau de leur migration et des fonctions effectrices. Non seulement cette paralysie augmente avec la sévérité de la maladie, mais elle persiste également après 3 jours suivant l’admission. De faibles doses de CS in vitro et in vivo dans le traitement du choc septique n’ont pas d’effet déterminant sur les PMN dans l’amélioration du pronostic des patients. Davantage de recherches seront nécessaires afin d’approfondir notre compréhension de l’impact d’un traitement aux CS sur les fonctions neutrophiliques dans un contexte septique. Ces derniers permettraient non seulement de mieux cibler leur utilisation dans le but d’arriver à un rapport bénéfique/risque avantageux dans le choc septique, mais aussi pour d’autres maladies inflammatoires. / Abstract : With the increasing rates of severe sepsis and refractory septic shock, there is still a challenge in mortality rates between 30 and 70 % at 28 days despite improved supportive care. Corticosteroids (CS) are a controversial supportive treatment in severe sepsis and refractory septic shock. They modulate the functions of PMN that are players in first line of immediate defence against the sepsis and associated to multiorgan failures. Results : Sepsis leads to a reduced phagocytic activity and ROS production at day 1 (D1) and day 3 (D3). It enhances the adhesion which increases with the severity of sepsis and persists until D3. In terms of degranulation, the sepsis increases the production and release of PTX3. Sepsis affects the phenotypic profile of PMN that increases the expressions of CD66b and ST2 at D1 and D3. It increases the CD64 expression but decreased at D3 in G2. No significant effect on chemotaxis was observed in D1, neither in D3. In G1, use of CS in vitro further delays apoptosis at D1 and D3, but is not showing any improvement in functions of PMN or in phenotypic profile. Conclusions : Sepsis induces an immune paralysis of PMN in their migration and effectives functions. Not only this paralysis increases with the severity of the sepsis, but it also persists after 3 days following the admission. Low doses of CS in vitro and in vivo in the treatment of septic shock have not determinant effect on PMN in improvement of the outcome of patients. More research is needed to learn more about the impacts of CS treatment on PMN functions in sepsis. This would contribute not only to ensure a better target ing of their use in order to achieve an advantageous benefits/risks ratio in septic shock, but also for others inflammatory diseases.

Neutrophil activation is the most important initial immune defense against invading microbes in newborn infants. The reduced neutrophil migration and uncontrolled regulation of reactive oxygen species (ROS) production observed in neonates, could result in a diminished infectious response or in tissue damage. The aims were to study neutrophil chemotactic response towards IL-8 and fMLP in term neonates; to examine neutrophil receptor expression involved in adhesion, migration, phagocytosis and complement after stimulation with IL-8 and fMLP in term neonates; and to investigate neutrophil production of ROS, induced by PMA and E.coli, after preincubation with IL-8 and fMLP in term and preterm newborn infants. Comparisons were made to neutrophils from healthy adults. Chemotaxis was distinguished from randomly migrating neutrophils, and the neutrophil migration distance and the number of migrating neutrophils per distance was evaluated. Neutrophils were labeled with antibodies to cell surface antigens (CD11b, CD18, CD65, CD15S, CD162, CD44, CD35, CD88, CD181, CD182 and CD64) after stimulation with IL-8 and fMLP. After preincubation of neutrophils with fMLP or IL-8 and stimulation with PMA or E.coli, respiratory burst was detected. The same analyses were also made in preterm infants (median 25+3weeks GA; range 23+0–29+2) within 3 days postnatal age. Neutrophils from neonates exhibited different migratory and receptor responses to IL-8 and fMLP, with a diminished response towards IL-8 in term newborn infants in terms of reduced chemotaxis and modulation of receptors involved in adhesion, chemotaxis, complement and phagocytosis as compared to adults. fMLP reduced PMA- and E.coli-induced respiratory burst in neutrophils from term neonates and adults. The reduced respiratory burst by fMLP may be a mechanism for reducing the detrimental effects of uncontrolled inflammation. Although a similar burst reduction was observed in preterm infants born &gt;25 weeks GA with fMLP, a diminished neutrophil respiratory burst modulation in very preterm infants cannot be excluded and requires further studies at different gestational and postnatal ages.

[pt] Neste trabalho avalia-se uma metodología de cálculo para a previsão da pressão de falha de um duto que contem colônias de corrosão, chamada Método das Linhas Ortogonais de Ruptura (MLOR). As colônias de corrosão são representadas por defeitos retangulares, localizados na superfície externa do duto. O objetivo do MLOR é ser mais exato que os métodos semi-empíricos da ASME e DNV utilizados até o momento. O MLOR também tem como objetivo evitar resultados não conservativos que podem ser obtidos com o método Mixed Type of Interacting (MTI). O MLOR apresenta outra forma de avaliar a perda de espessura efetiva de um grupo de defeitos. Ele propõe que se tracem linhas representativas do caminho pelo qual a ruptura do duto tem maior possibilidade de ocorrer, usando linhas paralelas às direções longitudinal e circunferencial do duto. Estas linhas são chamadas de linhas ortogonais de ruptura (LOR). Também considera-se o emprego de um fator de resistência circunferencial f no cálculo de uma espessura efetiva para a colônia. Este fator multiplica somente os comprimentos das LOR que estiverem na direção circunferencial do duto. O material íntegro existente entre dois defeitos é considerado na resistência à ruptura por meio da seleção de um caminho crítico que une os defeitos retangulares e que usa as direções longitudinal e circunferencial. Para a avaliação do MLOR usou-se pressões de falha para tubos com colônias de defeitos determinados experimentalmente e já publicados, além de simulações numéricas feitas pelo método dos elementos finitos (MEF), utilizando-se para isto o software comercial ANSYS. Por fim, neste trabalho concluiu-se que o MLOR apresentou bons resultados (máximos erro médio igual a -0.14 por cento e desvio padrão do erro igual a 3.53 por cento) quando comparados com os resultados experimentais e numéricos, já publicados, de nove corpos de provas em tamanho real. / [en] This dissertation comprises the evaluation of a new calculation methodology developed to predict the burst pressure of pipeline segments containing corrosion colonies. The new methodology is called Method of Orthogonal Lines Rupture (MLOR). The corrosion colonies are represented by rectangular defects, located on the outer surface of the pipeline segment. The objective of MLOR is to determine more accurate results than those calculated by the semi-empirical methods of ASME and DNV. The MLOR has also the objective of avoiding non-conservative results that can be obtained with the Mixed Type Interacting method (MTI). The MLOR presents a new way to assess the loss of effective thickness of a group of defects. It proposes the drawing of lines parallel to the longitudinal and circumferential directions that intend to represent the path by which the rupture of the pipeline is more likely to occur. These lines are called Orthogonal Lines of Rupture (LOR). It is also considered the employment of a strength circumferential factor f in the calculation of the effective thickness of the colony. This factor multiplies only the lengths of the LOR which are associated with the circumferential direction of the pipeline. Using that, the intact material existing between two defects is considered in the calculation of the rupture resistance. The critical path connects the rectangular defects using lines parallel to the longitudinal and circumferential directions. The evaluation of the MLOR was accomplished by comparing its burst pressure calculations with already published results determined for nine full scale tests carried out with specimens that contained specially designed and constructed colonies of defects. The comparisons encompassed those experimentally published test results and also results determined by numerical simulations that employed the finite element method (ANSYS commercial software). Finally, the dissertation concludes that the MLOR showed good results (maximum average error equal to -0.14 percent and standard deviation of the error equal to 3.53 percent) compared with experimental and numerical results.

INTRODUÇÃO: A ativação da NADPH oxidase de neutrófilos requer o acoplamento das subunidades citosólicas p47phox, p67phox, p40phox e Rac2 ao componente de membrana citocromo b558. Em trabalhos anteriores, nós mostramos que as isoformas vasculares da oxidase são reguladas pela proteína dissulfeto isomerase (PDI), uma chaperona redox. Neste trabalho, nós utilizamos um sistema cellfree semirecombinante como ferramenta para investigar o papel da PDI na ativação da NADPH oxidase do neutrófilo. RESULTADOS: Inibidores da PDI, scrambled RNAse (100g/mL) ou bacitracina (1mM), praticamente suprimiram a geração de superóxido. Para avaliação dos efeitos do estado redox da PDI sobre a atividade da oxidase, amostras de PDI foram previamente oxidadas (H2O2; 0,5 mM) ou reduzidas (DTT; 0,5 mM). A PDI oxidada (100 nM) aumentou a produção de superóxido em aproximadamente 30%, enquanto a mesma concentração de PDI reduzida promoveu efeito inverso, inibindo a atividade do complexo. A adição de um peptídeo contendo a seqüência peptídica do sítio ativo da PDI inibiu a produção de superóxido em 70%. Dados de imunolocalização e colocalização demonstraram que a interação da PDI com a subunidade p47phox parece ser intensificada pelo estímulo com PMA e envolvem modificações do estado redox de ambas as proteínas. CONCLUSÕES: Nossos dados confirmam a associação física e funcional entre a PDI e o complexo NADPH oxidase. Além disso, sugerem que a PDI exerça um importante papel como fator de regulação redox da ativação da oxidase. / Activation of the leukocyte NADPH oxidase requires the assembly of the cytosolic subunits p47phox, p67phox and p40phox and Rac2 with the membranebound cytochrome b558. We have previously shown that the vascular oxidase is regulated by the redox chaperone protein disulfide isomerase (PDI). Taking advantage of the semirecombinant cellfree system, we sought to investigate the role of PDI in the activation of neutrophil NADPH oxidase. The PDI thiol inhibitors scrambled RNase (100g/mL) or bacitracin (1mM), almost suppressed superoxide generation. In order to investigate if the redox status of PDI thiols could modulate superoxide generation, PDI was oxidized or reduced by treatment with H2O2 (0.5mM) or DTT (1mM), respectively. Oxidized PDI increased by 30% superoxide production, while reduced PDI diminished superoxide generation also in 30%. The addition of a peptide (1M) containing PDI´s exact active site sequence inhibited superoxide production by 70 %. Immuno and colocalization data demonstrated the interaction of PDI with the subunit p47phox to be intensified by PMA stimulation and to involve redox status exchange of both proteins. Our data confirm the physical and functional association between PDI and the oxidase complex. Moreover, we show a relevant role for PDI as a redoxdependent supportive factor for NADPH oxidase activation.

Os solos ácidos (pH < 5,0) representam cerca de 40 % das áreas agricultáveis no mundo. Nestes solos ocorre a solubilização de formas tóxicas de alumínio que inibe o crescimento radicular. Independente da presença do Al, o baixo pH pode ser tóxico à raiz, afetando a viabilidade celular no ápice e o crescimento radicular. Há evidências de que o estresse por H+ e/ou Al³+ afetam a parede celular. Por outro lado, modificações na parede podem determinar o grau de tolerância da planta quando submetidos a estes estresses. Assim, utilizou-se de duas abordagens para investigar se possíveis modificações na parede celular melhorariam o crescimento e viabilidade celular na exposição a H+ e Al³+. Na primeira, raízes de plantas do cultivar Micro-Tom (MT) de tomateiro (Solanum lycopersicum L.), com 2 e 13 dias de desenvolvimento, foram expostas de forma direta ou gradual ao baixo pH. Na segunda abordagem, as raízes foram submetidos a um tratamento hipo-osmótico antes de serem expostas a pH 4,0 ou 4,5 + Al. Em plantas com 2 e 13 dias, a exposição gradual foi realizada alterando o pH ao longo de 12 e 24 h, respectivamente. No tratamento hipo-osmótico (priming), as plantas foram transferidas de uma solução de alta osmolaridade (150 mM) para uma com baixa osmolaridade (0,5 mM), a pH 5,8, por 0; 0,5; 1 e 2 h antes de serem expostas a pH 4,0 ou 4,5 + Al por 12h. Como controles, raízes não receberam tratamento osmótico ou foram mantidas continuamente em alta osmolaridade. O crescimento de raízes expostas diretamente a pH 4,5 foi cerca de metade do controle a pH 5,8 e a pH 4,0 foi nulo. Ao contrário do esperado, na exposição gradual a pH 4,5, as raízes cresceram menos do que aquelas expostas diretamente a este pH e a pH 4,0 o crescimento continuou insignificante. No entanto, raízes expostas gradualmente ao pH 4,0 mantiveram a viabilidade das células do ápice, ao contrário daquelas expostas diretamente. Assim, a redução do crescimento radicular pela exposição a baixo pH pode ser uma resposta gerada pela própria planta, não sendo necessariamente decorrente da ação direta do pH. O priming hipo-osmótico antes da exposição a pH 4,0 permitiu a manutenção da viabilidade celular e um crescimento radicular de até 38% das raízes controle a pH 5,8, enquanto que nos controles a pH 4,0 as células morreram e o crescimento foi praticamente nulo. Em pH 4,5 + 5 ?M de Al o priming não reverteu a inibição do crescimento radicular, indicando que as respostas para H+ e Al³+ são diferentes. Ficou evidente que a atividade de GPX está envolvida nas respostas encontradas tanto na exposição gradual a baixo pH como no tratamento hipo-osmótico anterior ao baixo pH, mas não foi possível determinar se é consequência ou uma das possíveis causas destas respostas. No seu conjunto, os dados indicam que possíveis mudanças na parede celular podem estar envolvidas na melhoria do crescimento radicular e viabilidade celular do ápice durante o estresse. / Acidic soils (pH <5.0) represent about 40% of the arable land in the world. In these soils, toxic aluminum becomes soluble and inhibits root growth. Regardless of Al, low pH is, in itself, also toxic, decreasing cell viability and root growth. There is evidence that H+ and Al3+ can affect the cell wall. Reversely, modifications in the wall may determine the degree of tolerance of roots subjected to these stresses. Therefore, we used two approaches to investigate whether possible changes in the cell wall improve growth and cell viability upon exposure to H + and Al³+. In the first approach, roots of plants of the Micro-Tom (MT) cultivar of tomato (Solanum lycopersicum L.), at 2 and 13 days of development, were exposed directly or gradually to low pH. In the second approach, the roots were subjected to hypoosmotic treatment prior to being exposed to pH 4.0 or 4.5 + Al. In 2- and 13-day plants, gradual exposure was achieved by changing the pH over a 12 and 24 h period, respectively. In the hypo-osmotic pre-treatment (priming), plants were transferred from a high osmolarity solution (150 mM) to another with low osmolarity (0.5 mM), at pH 5.8, for 0, 0.5, 1 and 2 h before being exposed to pH 4.0 or 4.5 + Al for 12h. As controls, roots did not receive any osmotic treatment or were maintained continuously at high osmolarity. Growth of roots exposed directly to pH 4.5 was about half that of control roots at pH 5,8 and at pH 4.0 root growth was suppressed. Different from expected, roots exposed gradually to pH 4.5 grew less than those exposed directly to pH 4.5 and at pH 4.0, root growth remained negligible. However, cell viability was maintained in roots exposed gradually to pH 4.0, unlike those exposed directly. Thus, decreased root growth upon exposure to low pH may be a response generated by the plant itself rather than the direct effect of pH. In roots subjected to hypo-osmotic priming prior to exposure to pH 4.0, cell viability was maintained and root growth was up to 38% of that of control roots at pH 5.8, whereas in control roots at pH 4.0, cell death occurred and root growth was insignificant. At pH 4.5 + 5 uM Al, priming did not reverse the inhibition of root growth, suggesting that responses to H+ and Al3+ are different. GPX was involved in responses to both gradual exposure to low pH and to hypo-osmotic treatment prior to low pH, but it was not possible to determine whether this was a consequence or one of the possible causes of these responses. Taken together, the data indicate that possible changes in the cell wall may be involved in improving root growth and cell viability of the root apex during stress.