The strength of the ultrafine-grained materials is increased with grain refinement, but it will also reduce the ductility. In the previous study, there are higher strength and better ductility for the copper with bimodal distribution of grain size. In this study, Ni with lamellar structure is fabricated by electrodeposition in order to explore the mechanical properties of the materials with bimodal distribution of grain size, which is obtained by controlling the grain size. From the result of EBSD analysis, it shows that the area ratio of coarse grains and fine grains is from 0.3 to 3 by changing the plating parameters. The average grain size of fine grains is about 0.5 £gm, and the maximum average grain size of coarse grains is up to 6.0 £gm. From the result of tensile test, the materials with 35% of micro-grains embedded regularly inside a matrix of ultrafine grains have better strength and ductility. When the area ratio of micro-grains is up to 62.5%, there is no difference in mechanical properties between the general electrodeposited materials and ones with bimodal distribution of grain size. For pure Ni, the enhancement of ductility for bimodal distribution of grain size is only in post uniform elongation. Otherwise, it is found that the strength and ductility of the material with lamellar structure are increased through the heat treatmeant under the appropriate temperature.

Arterial thrombus forms from the capture and accumulation of circulating platelets on a stenosis. As the thrombus grows, the lumen becomes further stenotic producing very high shear rates as the blood velocities increase through the narrowed cross-section. This study explores the molecular binding conditions that may occur under these pathologic shear conditions where circulating platelets must adhere quickly and with strong bonds. Platelets binding in an arterial stenosis of >75% are subject to drag forces exceeding 10,000 pN. This force can be balanced by 100 simultaneous GPIb-vWFA1 bonds of 100 pN each. The number and density of GPIb on platelets is sufficiently high; however, platelet capture under high shear would require the density of A1 receptors to be increased to over 416 per square micron. A computational model is used to determine platelet capture as a function of shear rate, surface receptor density, surface contact and kinetic binding rate. A1 density could be increased by a combination of vWF events of: i) plasma vWF attach to the thrombus surface and elongate under shear; ii) the elongated vWF strands create a net with 3-D pockets; and iii) additional vWF is released from mural platelets by activation under shear. With all three events, A1 density matches the existing high GPIbα densities to provide sufficient multivalency for capture at 100,000 s-1 with greater than 170 bonds per platelet. If the on-rate is greater than 108 M-1s-1, then a platelet could be captured within 15 microseconds, the amount of time available to form bonds before the platelet is swept away. This mechanism of platelet capture allows for the rapid platelet accumulation in atherothombosis seen clinically and in high shear experiments.

Ectotherms such as frogs must either function within environments with temperatures amenable to their physiological needs, or find means to reduce the impact of temperature on their activities. Recent studies on reptile and amphibian feeding have shown convergent use of elastic recoil to drive feeding movements, thereby decoupling temperature's effects on muscle from movement and allowing the animals to feed over broader temperature ranges. Rana pipiens specimens (n=5) were exposed to three ambient temperatures (10°, 15°, and 25° C) at which feeding behavior was imaged at 6000 Hz. The image sequences yielded detailed kinematic and dynamic information for jaw, tongue, and body movements, including velocity, acceleration, power, duration, and excursion. Previously published studies have examined feeding in ranid frogs; however, those studies employed slower frame rates that did not permit analysis of instantaneous accelerations and velocities, and depressor and jaw-tongue complex mass specific power outputs in Rana feeding have not yet been established. Specimens were dissected for morphological measurement and calculation of mass-specific dynamics relative to the m. depressor mandibulae and the center of mass of the jaw-tongue complex. Previous studies on tongue projection in Bufo terrestris have shown that the rapid jaw depression that inertially elongates the tongue relies on elasticity in the depressor muscles. Further, because this movement is elastically driven, it is less sensitive to temperature than a completely muscle-driven movement would be. Because Rana also feeds through inertial elongation of the tongue (as does Bufo, in which the mechanism is convergent), I hypothesized that Rana would demonstrate thermal insensitivity in its feeding kinematics and dynamics in a pattern similar to that documented in Bufo. Experimental results indicated that portions of the feeding cycle related to the initial, ballistic phase were at least moderately thermally insensitive. At all temperatures studied, Rana reached approximately half of the depressor mass-specific power of Bufo, demonstrating that Bufo's depressor mass-specific power output is not the minimum value necessary for inertial elongation. I further hypothesize that thermal independence and power output in excess of that achievable by muscle alone during the initial, ballistic mouth opening phase of feeding suggests the involvement of an elastic mechanism convergent with that of Bufo terrestris.

Στην παρούσα εργασία εξετάζεται η μοντελοποίηση στοιχείων από οπλισμένο σκυρόδεμα και συγκεκριμένα υποστυλώματα μονολιθικά αλλά και ενισχυμένα με την μέθοδο των πεπερασμένων στοιχείων. Τα δοκίμια τα οποία εξετάζονται έχουν υποβληθεί σε ανακυκλιζόμενη φόρτιση στο Εργαστήριο Κατασκευών του Τμήματος Πολιτικών Μηχανικών του Πανεπιστημίου Πατρών και τα αποτελέσματα των πειραματικών δοκιμών χρησιμοποιούνται για τον έλεγχο της αξιοπιστίας των αναλύσεων. Τα μοντέλα που κατασκευάστηκαν έχουν την δυνατότητα να λαμβάνουν υπόψιν την σχετική ολίσθηση μεταξύ του χάλυβα οπλισμού και του σκυροδέματος και επομένως και την εξόλκευση των ράβδων οπλισμού από το πέδιλο. Ωστόσο στα ενισχυμένα δοκίμια εξετάζονται διαφορετικοί τρόποι μοντελοποίησης της διεπιφάνειας μεταξύ παλαιού και νέου σκυροδέματος. Στο πρώτο κεφάλαιο της εργασίας παρουσιάζονται ορισμένα γενικά θεωρητικά θέματα σχετικά με τις ενισχύσεις και επισκευές στοιχείων από οπλισμένο σκυρόδεμα και κυρίως υποστυλωμάτων. Στο δεύτερο κεφάλαιο αναφέρονται λίγα πράγματα για την μέθοδο των πεπερασμένων στοιχείων και στην συνέχεια γίνεται μια σύντομη περιγραφή του προγράμματος πεπερασμένων στοιχείων ANSYS και των δυνατοτήτων που έχει. Στο τρίτο κεφάλαιο υπάρχει λεπτομερής περιγραφή των παραδοχών καθώς και των στοιχείων που χρησιμοποιούνται για την μοντελοποίηση στοιχείων από οπλισμένο σκυρόδεμα. Στο τέταρτο κεφάλαιο πραγματοποιείται μία βιβλιογραφική ανασκόπηση με σκοπό την τεκμηρίωση παραδοχών που χρησιμοποιούνται για την καλύτερη πρόβλεψη της συμπεριφοράς στοιχείων από οπλισμένο σκυρόδεμα. Στο πέμπτο κεφάλαιο παρουσιάζονται δύο αναλυτικές προσεγγίσεις του φαινομένου της εξόλκευσης των ράβδων οπλισμού από το πέδιλο. Η περιγραφή των πειραματικών δοκιμών που πραγματοποιήθηκαν στο Εργαστήριο Κατασκευών του Τμήματος Πολιτικών Μηχανικών του Πανεπιστημίου Πατρών, τα αποτελέσματα των οποίων χρησιμοποιούνται, για τον έλεγχο της αξιοπιστίας των αναλύσεων, πραγματοποιείται στο κεφάλαιο έξι. Στο έβδομο κεφάλαιο παρουσιάζονται τα αποτελέσματα των αναλύσεων που πραγματοποιήθηκαν για τρία μονολιθικά δοκίμια. Επιπλέον εξετάζεται και ένας εναλλακτικός απλοποιητικός τρόπος μοντελοποίησης με τον οποίο θεωρείται πλήρης συνάφεια χάλυβα – σκυροδέματος. Χρησιμοποιώντας την παραδοχή αυτή, αγνοείται το φαινόμενο της εξόλκευσης των ράβδων από το πέδιλο. Για το λόγο αυτό πραγματοποιείται και μια αναλυτική προσέγγιση της πρόσθετης μετατόπισης λόγω της εξόλκευσης και προκύπτουν τα τελικά αποτελέσματα τα οποία είναι αντίστοιχα με αυτά στα οποία γίνεται θεώρηση σχετικής ολίσθησης χάλυβα – σκυροδέματος. Στο όγδοο κεφάλαιο εξετάζονται πέντε ενισχυμένα δοκίμια. Παρουσιάζονται τρεις διαφορετικοί τρόποι μοντελοποίησης της διεπιφάνειας μεταξύ παλαιού – νέου σκυροδέματος γίνονται, ενώ προσομοιώνεται και η δράση βλήτρου κάνοντας χρήση ειδικών πολυγραμμικών ελατηρίων. Στην συνέχεια παρουσιάζονται τέσσερις διαφορετικού τρόποι για την έμμεση προσομοίωση της επίδρασης της ανακύκλισης στην συμπεριφορά της διεπιφάνειας. Επιπλέον εξετάζεται και η επίδραση της ανακυκλιζόμενης φόρτισης στην δράση του βλήτρου. Τα αποτελέσματα συγκρίνονται τόσο με τα αντίστοιχα πειραματικά όσο και με αυτά στα οποία αγνοείται η επίδραση της ανακύκλισης. Τέλος στο ένατο κεφάλαιο παρουσιάζονται τα τελικά συμπεράσματα που προέκυψαν καθώς και οι προτάσεις για μελλοντική έρευνα. Τα συμπεράσματα που προέκυψαν από την παρούσα εργασία είναι αρχικά, ότι η επιδραση του φαινομένου της εξόλκευσης στην συμπεριφορά των υποστυλωμάτων είναι αρκετά σημαντική. Ωστόσο τα αποτελέσματα που προέκυψαν από την ανάλυση που συμπεριλάμβανε το φαινόμενο αυτό καθώς και τα αντίστοιχα που προέκυψαν από τον συνδυασμό της απλοποιητικής ανάλυσης (πλήρη συνάφεια χάλυβα – σκυροδέματος) σε συνδυασμό με την αναλυτική μέθοδο είναι αρκετά ικανοποιητικά και προσεγγίζουν σχετικά καλά την περιβάλλουσα που προκύπτει από τα πειραματικά αποτελέσματα. Από τα αποτελέσματα που προέκυψαν για τα ενισχυμένα δοκίμια φαίνεται η επίδραση των χαρακτηριστικών της διεπιφάνειας στην συμπεριφορά των ενισχυμένων στοιχείων καθώς και η συμβολή των βλήτρων τόσο στην γενικότερη συμπεριφορά όσο και στην μείωση της ολίσθησης στην διεπιφάνεια. Ωστόσο σύμφωνα με τα αποτελέσματα η επίδραση της ανακύκλισης της φόρτισης είναι αρκετά σημαντική και επηρεάζει την συμπεριφορά του στοιχείου. / This thesis examines the simulation of reinforced concrete elements. In particular, the finite element method is used to investigate the behaviour of monolithic and strengthened columns that were tested under cyclic loading in the Structural Laboratory of the Department of Civil Engineering at the University of Patras. The reliability of the analytical models is examined by comparing experimental and numerical results. The numerical models created included modelling the sliding between the reinforcing steel and the concrete, the consequence of bar elongation and the total extension of a reinforcing bar at a particular point in relation to the surrounding concrete. Therefore, for strengthened specimens, different ways of modelling the interface between old and new concrete are examined. The first chapter presents some theoretical models for the strengthening and repair of reinforced concrete elements with particular reference to reinforced concrete columns. A brief review of the finite element method and the finite element program ANSYS is presented in the second chapter. The third chapter presents a detailed description of the basic assumptions and the elements that were used to model reinforced concrete members. A literature review is presented in the fourth chapter in order to explain assumptions and to describe the elements that were used for the models. Two analytical approaches for the phenomenon of bar elongation are presented in the fifth chapter. A description of the experimental tests performed in the Structural Laboratory of the Department of Civil Engineering at the University of Patras and the experimental results that were used to examine the reliability of the numerical results is presented in chapter six. In the seventh chapter, the results of the analysis of three monolithic specimens are presented. In this way, a simplified method is examined by considering a perfect bond between the steel and the concrete. By using this assumption, the phenomenon of bar elongation is neglected. In addition, an analytical approach for the supplementary deflection due to bar elongation is presented and the total result, including the supplement deflection, is similar to that using the assumption of relative slip between the steel and the concrete. Five strengthened columns are investigated in the eighth chapter. Three different methods of modelling the interface between the old and the new concrete are proposed and the presence of dowels is simulated by using special multi-linear springs. Therefore, four different processes for the simulation of the effect of cyclic loading on the behaviour at the interface are proposed. Furthermore, the effect of cyclic loading on the behaviour of dowels is examined. The results are compared to the relevant experimental results and to results where the effects of cyclic loading are neglected. Finally, the ninth chapter presents results and recommendations for further research. One conclusion that arises from this thesis is that the effect of bar elongation on the behaviour of reinforced concrete columns is quite significant. It was found that the results from the analysis that took into account bar elongation due to relative slippage and the analysis using the simplified method (perfect bond between steel and concrete) in combination with the supplementary deflection due to the bar elongation calculated using analytical methods are similar to the experimental results. Using the results of the strengthened specimens that have been presented, the effect of the properties at the interface and the contribution of the dowels on the behaviour of the strengthened specimens and in the reduction of sliding on the interface can been noted. However, according to the results, it must be stressed that the effects of cyclic loading are significant and affects the behaviour of the model.

Many viruses can produce multiple proteins from a single mRNA sequence by encoding the proteins in overlapping genes. One mechanism that causes the ribosomes of infected cells to decode both genes is –1 programmed ribosomal frameshifting. In this process, structural elements of the viral mRNA signal the ribosome to shift reading frames at a specific point. Although –1 frameshifting has been recognized since 1985, the mechanism is not well understood. I have developed a stochastic model of mRNA translation that includes the possibility of a –1 frameshift at any codon. The transition probabilities between states of the model are based on the energetics of local molecular interactions. The model reproduces observed translation rates as well as both the location and efficiency of frameshift events in the HIV-1 gag-pol sequence. In this work, the model is used to predict changes in the frameshift efficiency due to mutations in the viral mRNA sequence or variations in relative tRNA abundances. The model is sensitive to the size of the translating ribosome and to assumptions about the unfolding pathway of the stimulatory structure. As knowledge in the field of RNA structure prediction grows, that knowledge can be incorporated into the model developed here to make improved predictions. The single-ribosome translation model has been extended to polysomes by including initiation and termination rates and an exclusion principle, and allowing the stimulatory structure to refold on an appropriate timescale. The predicted frameshift efficiency for a given mRNA can be tuned by varying the ribosome density on the mRNA. This finding affects the interpretation of frameshift efficiencies measured in the lab. In the parameter regime where translation is initiation-limited, the frameshift efficiency also depends on the structure refolding rate, which determines the availability of the downstream structure for stimulating –1 frameshifts. Furthermore, there is a trade-off between frameshift efficiency and protein synthesis rate.

No description available.

In the seismic design of reinforced concrete frames, plastic hinges are allocated to beams such that a ductile beam-sway mechanism will form in preference to other less ductile mechanisms in the event of a major earthquake. This is achieved by ensuring that the flexural strength of columns is greater than that corresponding to the maximum likely flexural strength of beam plastic hinges. Recent experimental studies in New Zealand have shown that elongation of ductile beam plastic hinges, and its interaction with nearby floor slab containing precast-prestressed floor units, increases the strength of beams much more than that specified in New Zealand and American Concrete standards. This level of strength enhancement has raised concern on the adequacy of the current design provisions. To further investigate this problem, a research project was initiated to examine the strength of beam plastic hinges in reinforced concrete frames containing precast-prestressed floor units. In this research, the strength of beam plastic hinges was assessed through experimental and analytical studies. A three-dimensional, one-storey, two-bay reinforced concrete moment resisting frame with prestressed floor units and cast-in-situ concrete topping was tested under quasi-static displacement-controlled cyclic loading. The experimental results provided insight into the mechanics associated with frame-floor interaction. Subsequently, improved design specifications were proposed based on the observed behaviour. To analytically predict the beam-floor interaction, a ductile reinforced concrete plastic hinge multi-spring element was developed and validated with experimental results from cantilever beam and frame sub-assembly tests reported in the literature. The comparisons have demonstrated the ability of the proposed plastic hinge element to predict the flexural, shear, axial, and most importantly, elongation response of ductile plastic hinges. The proposed plastic hinge element was implemented into an analytical model to simulate the behaviour of the frame-floor sub-assembly tested in this research. Specially arranged truss-like elements were used to model the linking slab (the region connecting the main beam to the first prestressed floor unit), where significant inelastic behaviour was expected to occur. The analytical model was found to be capable of predicting the non-linear hysteretic response and the main deformation mechanisms in the frame-floor sub-assembly test. The analytical frame-floor model developed in this study was used to examine the effect of different structural arrangements on the cyclic behaviour of frames containing prestressed floor units. These analyses indicated that slab reinforcement content, the number of bays in a frame and the position of frame in a building (i.e., perimeter or internal frame) can have a significant influence on the strength and elongation response of plastic hinges.

Molecular diagnostics is a fast growing field with new technologies being developed constantly. There is a demand for more sophisticated molecular tools able to detect a multitude of molecules on a single molecule level with high specificity, able to distinguish them from other similar molecules. This becomes very important for infectious diagnostics with the increasing antibiotic resistant viruses and bacteria, in gene based diagnostics and for early detection and more targeted treatments of cancer. For increased sensitivity, simplicity, speed and user friendliness, novel readouts are emerging, taking advantage of new technologies being discovered in the field of nanotechnology.  This thesis, based upon four papers, examines two novel electrical readouts for amplified single molecule detection. Target probing is based upon the highly specific amplification technique rolling circle amplification (RCA). RCA enables localized amplification resulting in a long single stranded DNA molecule containing tandem repeats of the probing sequence as product. Paper I demonstrates sensitive detection of bacterial genomic DNA using a magnetic nanoparticles-based substrate-free method where as few as 50 bacteria can be detected. Paper II illustrates a new sensor concept based on the formation of conducting molecular nanowires forming a low resistance circuit. The rolling circle products are stretched to bridge an electrode gap and upon metallization the resistance drops by several orders of magnitude, resulting in an extremely high signal to noise ratio. Paper III explores a novel metallization technique, demonstrating the efficient incorporation of boranephosphonate modified nucleotides during RCA.  In the presence of a silver ion solution, defined metal nanoparticles are formed along the DNA molecule with high spatial specificity. Paper IV demonstrates the ability to manipulate rolling circle products by dielectrophoresis. In the presence of a high AC electric field the rolling circle products stretch to bridge a 10 µm electrode gap.

Developmental processes are carefully controlled at the level of transcription to ensure that the fertilized egg develops into an adult organism. The mechanisms that controls transcription of protein-coding genes ultimately ensure that the Pol II machine synthesizes mRNA from the correct set of genes in every cell type. Transcriptional control involves Pol II recruitment as well as transcriptional elongation. Recent genome-wide studies shows that recruitment of Pol II is often followed by an intermediate step where Pol II is halted in a promoter-proximal paused configuration. The release of Pol II from promoter-proximal pausing is thus an additional and commonly occurring mechanism in metazoan gene regulation. The serine kinase P-TEFb is part of the Super Elongation Complex that regulates the release of paused Pol II into productive elongation. However, little is known about the role of P-TEFb mediated gene expression in development. We have investigated the function of P-TEFb in early Drosophila embryogenesis and find that P-TEFb and other Super Elongation Complex subunits are critical for activation of the most early expressed genes. We demonstrate an unexpected function for Super Elongation Complex in activation of genes with non-paused Pol II. Furthermore, the Super Elongation Complex shares phenotypes with subunits of the Mediator complex to control the activation of essential developmental genes. This raises the possibility that the Super Elongation Complex has an unappreciated role in the recruitment of Pol II to promoters. The unique chromatin landscape of each cell type is comprised of post-translational chromatin modifications such as histone methylations and acetylations. To study the function of histone modifications during development, we depleted the histone demethylase KDM4A in Drosophila to evaluate the role of KDM4A and histone H3 lysine 36 trimethylation (H3K36me3) in gene regulation. We find that KDM4A has a male-specific function and regulates gene expression both by catalytic-dependent and independent mechanisms. Furthermore, we used histone replacement to investigate the direct role of H3K14 acetylation in a multicellular organism. We show that H3K14 acetylation is essential for development, but is not cell lethal, suggesting that H3K14 acetylation has a critical role in developmental gene regulation. This work expands our knowledge of the mechanisms that precisely controls gene regulation and transcription, and in addition highlights the complexity of metazoan development. / <p>At the time of the doctoral defense, the following papers were unpublished and had a status as follows: Paper 1: Manuscript. Paper 3: Manuscript.</p>

Ribosomal stalk proteins are known to play important role in protein synthesis. The ‘stalk’, an extended structure on the large subunit of the ribosome is composed mainly of two to three dimers of L12 and one L10 protein, which forms the base of the stalk. In E. coli, four copies of L12 molecules exist as dimer of dimers forming the pentameric L8 complex together with L10. This thesis is a collection of four interlinked studies on the structure, function and application of the ribosomal stalk protein L12. In the first study, we have mapped the interaction sites of the four major translation GTPase factors (IF2, EF-Tu, EF-G &amp; RF3) on L12 molecule using heteronuclear NMR spectroscopy. Surprisingly, all these factors produced an overlapping interaction map spanning two α-helices on the C terminal domain of L12, thereby suggesting a general nature of the interaction between L12 and the GTPase factors. L12 is known to stimulate GTPase activity of the elongation factors EF-Tu and EF-G. Here, we have clarified the role of L12 in IF2 mediated initiation of protein synthesis. Our data suggest that rapid subunit association requires a specific interaction between the L12 protein on the 50S and IF2·GTP on the 30S preinitiation complex. We have also shown that L12 is not a GAP for IF2 and GTP hydrolysis triggers IF2 release from the 70S initiation complex. The next question we have addressed is why multiple copies of L12 dimer are needed on the ribosome. For this purpose, we created a pure E. coli strain JE105, where the terminal part of rplJ gene coding for the binding site of one L12 dimer on protein L10 was deleted in the chromosomal locus. Using ribosomes with single L12 dimer we have observed that the rate of the initiation and elongation involving IF2 and EF-G gets most compromised, which in turn decreases the growth rate of the bacteria.  This study also indicates that L12 can interact with different GTPase factors in a specialized manner. Lastly, we have developed an application making advantage of the multiple L12 dimers on the ribosome. By inserting a (His)6-tag at the C-terminus of the L12 protein we have created a novel E. coli strain (JE28), where all ribosomes are tetra-(His)6-tagged. Further, we have developed a single step method for purification of the active (His)6-tagged ribosomes from JE28.