Prediction of Sudden Cardiac Arrest for Patients with Congestive Heart Failure

Thesis (Ph.D.)--University of Washington, 2016-07

Navigating a corpus of journal papers using Handles

For some years now the Internet and World Wide Web communities have envisaged moving to a next generation of Web technologies by promoting a globally unique, and persistent, identifier for identifying and locating many forms of published objects . These identifiers are called Universal Resource Names (URNs) and they hold out the prospect of being able to refer to an object by what it is (signified by its URN), rather than by where it is (the current URL technology). One early implementation of URN ideas is the Unicode-based Handle technology, developed at CNRI in Reston Virginia. The Digital Object Identifier (DOI) is a specific URN naming convention proposed just over 5 years ago and is now administered by the International DOI organisation, founded by a consortium of publishers and based in Washington DC. The DOI is being promoted for managing electronic content and for intellectual rights management of it, either using the published work itself, or, increasingly via metadata descriptors for the work in question. This paper describes the use of the CNRI handle parser to navigate a corpus of papers for the Electronic Publishing journal. These papers are in PDF format and based on our server in Nottingham. For each paper in the corpus a metadata descriptor is prepared for every citation appearing in the References section. The important factor is that the underlying handle is resolved locally in the first instance. In some cases (e.g. cross-citations within the corpus itself and links to known resources elsewhere) the handle can be handed over to CNRI for further resolution. This work shows the encouraging prospect of being able to use persistent URNs not only for intellectual property negotiations but also for search and discovery. In the test domain of this experiment every single resource, referred to within a given paper, can be resolved, at least to the level of metadata about the referred object. If the Web were to become more fully URN aware then a vast directed graph of linked resources could be accessed, via persistent names. Moreover, if these names delivered embedded metadata when resolved, the way would be open for a new generation of vastly more accurate and intelligent Web search engines.

The MUSE Machine -- an Architecture for Structured Data Flow Computation

Computers employing some degree of data flow organisation are now well established as providing a possible vehicle for concurrent computation. Although data-driven computation frees the architecture from the constraints of the single program counter, processor and global memory, inherent in the classic von Neumann computer, there can still be problems with the unconstrained generation of fresh result tokens if a pure data flow approach is adopted. The advantages of allowing serial processing for those parts of a program which are inherently serial, and of permitting a demand-driven, as well as data-driven, mode of operation are identified and described. The MUSE machine described here is a structured architecture supporting both serial and parallel processing which allows the abstract structure of a program to be mapped onto the machine in a logical way.

Nanostructured catalysts for the development of the hydrogen economy

La catalyse joue un rôle essentiel dans de nombreuses applications industrielles telles que les industries pétrochimique et biochimique, ainsi que dans la production de polymères et pour la protection de l’environnement. La conception et la fabrication de catalyseurs efficaces et rentables est une étape importante pour résoudre un certain nombre de problèmes des nouvelles technologies de conversion chimique et de stockage de l’énergie. L’objectif de cette thèse est le développement de voies de synthèse efficaces et simples pour fabriquer des catalyseurs performants à base de métaux non nobles et d’examiner les aspects fondamentaux concernant la relation entre structure/composition et performance catalytique, notamment dans des processus liés à la production et au stockage de l’hydrogène. Dans un premier temps, une série d’oxydes métalliques mixtes (Cu/CeO2, CuFe/CeO2, CuCo/CeO2, CuFe2O4, NiFe2O4) nanostructurés et poreux ont été synthétisés grâce à une méthode améliorée de nanocasting. Les matériaux Cu/CeO2 obtenus, dont la composition et la structure poreuse peuvent être contrôlées, ont ensuite été testés pour l’oxydation préférentielle du CO dans un flux d’hydrogène dans le but d’obtenir un combustible hydrogène de haute pureté. Les catalyseurs synthétisés présentent une activité et une sélectivité élevées lors de l’oxydation sélective du CO en CO2. Concernant la question du stockage d’hydrogène, une voie de synthèse a été trouvée pour le composét mixte CuO-NiO, démontrant une excellente performance catalytique comparable aux catalyseurs à base de métaux nobles pour la production d’hydrogène à partir de l’ammoniaborane (aussi appelé borazane). L’activité catalytique du catalyseur étudié dans cette réaction est fortement influencée par la nature des précurseurs métalliques, la composition et la température de traitement thermique utilisées pour la préparation du catalyseur. Enfin, des catalyseurs de Cu-Ni supportés sur silice colloïdale ou sur des particules de carbone, ayant une composition et une taille variable, ont été synthétisés par un simple procédé d’imprégnation. Les catalyseurs supportés sur carbone sont stables et très actifs à la fois dans l’hydrolyse du borazane et la décomposition de l’hydrazine aqueuse pour la production d’hydrogène. Il a été démontré qu’un catalyseur optimal peut être obtenu par le contrôle de l’effet bi-métallique, l’interaction métal-support, et la taille des particules de métal.

Vegetables production in NW Portugal, agriculture practices and groundwater quality

In NW of Portugal, the region between Esposende and Vila do Conde was established into a unique system called masseiras; masseiras are small fields that were created at the beginning of XX century by removing sand from dunes. Since the 80’s sand between closed masseiras has been removed giving way for larger fields, the “enlarged masseira with greenhouses”. This region is part of vulnerable zone nº1 (VZ1). Nowadays, the masseiras have almost disappeared; they had been replaced by “enlarged masseiras with plastic greenhouses” exploited by a new generation of growers. As water quality is an indicator of agriculture practices, 8 wells were selected and water samples were collected on four dates from September 2009 to May 2010. Laboratorial analysis was performed on nitrates and 28 pesticides. The results confirm that water in VZ1 is contaminated with nitrates (as it was expected) and also with pesticides. The water was contaminated in both dug wells and drilled wells all year round. Masseiras’ wells have more nitrates than greenhouses’ wells, probably due to poor agricultural practices used by growers who still employ high quantities of fertilizers and water. Pesticides detected in water samples include some that have been sprayed in the field and others that have not. Some forbidden substances were found. Our results confirm that, in VZ1, there is a diffusion contamination, which origin is unknown. In this communication, we put in picture the history of masseiras fields: how masseiras fields have been created and how they have disappeared; what trends exist in pest management strategies and the use of fertilizers, pesticides and water resources. These results reinforce the need to change the agricultural system in this region of traditional vegetable production.

Efficient and Durable Vaccine against Intimin β of Diarrheagenic E. Coli Induced by Clay Nanoparticles

Improved strategies are urgently required to control infections with enterohemorrhagic Escherichia coli and enteropathogenic E. coli, two dominant zoonotic enteric pathogens responsible for a wide spectrum of illnesses as well as deaths of human being, with tremendous financial cost worldwide. The present study investigates the capacity of two clay nanoparticles (NPs) with opposite surface charges, namely synthetic layered double hydroxide (LDH) and hectorite (HEC) NPs as adjuvants to promote strong immune responses against the infections. Here both LDH and HEC NPs are showed to be able to carry an appreciable amount of Intimin β (1.1 and 4.4 mg per mg clay nanomaterials, respectively) and significantly facilitate antigen uptake by antigen-presenting cells. Remarkably, these clay NPs induce strong antibody and cell-mediated immune responses, which are much higher than that by the potent adjuvant, QuilA. Furthermore, these strong immune responses are well maintained for at least four months in the mouse model, during which there are no changes in histopathology of the animal organs. Collectively these data demonstrate the suitability of LDH and HEC NPs as useful adjuvants in new-generation vaccine formulations to control various infectious diseases.

Microfluidic platforms for the characterization of in meso membrane protein crystallization

Membrane proteins, which reside in the membranes of cells, play a critical role in many important biological processes including cellular signaling, immune response, and material and energy transduction. Because of their key role in maintaining the environment within cells and facilitating intercellular interactions, understanding the function of these proteins is of tremendous medical and biochemical significance. Indeed, the malfunction of membrane proteins has been linked to numerous diseases including diabetes, cirrhosis of the liver, cystic fibrosis, cancer, Alzheimer's disease, hypertension, epilepsy, cataracts, tubulopathy, leukodystrophy, Leigh syndrome, anemia, sensorineural deafness, and hypertrophic cardiomyopathy.1-3 However, the structure of many of these proteins and the changes in their structure that lead to disease-related malfunctions are not well understood. Additionally, at least 60% of the pharmaceuticals currently available are thought to target membrane proteins, despite the fact that their exact mode of operation is not known.4-6 Developing a detailed understanding of the function of a protein is achieved by coupling biochemical experiments with knowledge of the structure of the protein. Currently the most common method for obtaining three-dimensional structure information is X-ray crystallography. However, no a priori methods are currently available to predict crystallization conditions for a given protein.7-14 This limitation is currently overcome by screening a large number of possible combinations of precipitants, buffer, salt, and pH conditions to identify conditions that are conducive to crystal nucleation and growth.7,9,11,15-24 Unfortunately, these screening efforts are often limited by difficulties associated with quantity and purity of available protein samples. While the two most significant bottlenecks for protein structure determination in general are the (i) obtaining sufficient quantities of high quality protein samples and (ii) growing high quality protein crystals that are suitable for X-ray structure determination,7,20,21,23,25-47 membrane proteins present additional challenges. For crystallization it is necessary to extract the membrane proteins from the cellular membrane. However, this process often leads to denaturation. In fact, membrane proteins have proven to be so difficult to crystallize that of the more than 66,000 structures deposited in the Protein Data Bank,48 less than 1% are for membrane proteins, with even fewer present at high resolution (< 2Å)4,6,49 and only a handful are human membrane proteins.49 A variety of strategies including detergent solubilization50-53 and the use of artificial membrane-like environments have been developed to circumvent this challenge.43,53-55 In recent years, the use of a lipidic mesophase as a medium for crystallizing membrane proteins has been demonstrated to increase success for a wide range of membrane proteins, including human receptor proteins.54,56-62 This in meso method for membrane protein crystallization, however, is still by no means routine due to challenges related to sample preparation at sub-microliter volumes and to crystal harvesting and X-ray data collection. This dissertation presents various aspects of the development of a microfluidic platform to enable high throughput in meso membrane protein crystallization at a level beyond the capabilities of current technologies. Microfluidic platforms for protein crystallization and other lab-on-a-chip applications have been well demonstrated.9,63-66 These integrated chips provide fine control over transport phenomena and the ability to perform high throughput analyses via highly integrated fluid networks. However, the development of microfluidic platforms for in meso protein crystallization required the development of strategies to cope with extremely viscous and non-Newtonian fluids. A theoretical treatment of highly viscous fluids in microfluidic devices is presented in Chapter 3, followed by the application of these strategies for the development of a microfluidic mixer capable of preparing a mesophase sample for in meso crystallization at a scale of less than 20 nL in Chapter 4. This approach was validated with the successful on chip in meso crystallization of the membrane protein bacteriorhodopsin. In summary, this is the first report of a microfluidic platform capable of performing in meso crystallization on-chip, representing a 1000x reduction in the scale at which mesophase trials can be prepared. Once protein crystals have formed, they are typically harvested from the droplet they were grown in and mounted for crystallographic analysis. Despite the high throughput automation present in nearly all other aspects of protein structure determination, the harvesting and mounting of crystals is still largely a manual process. Furthermore, during mounting the fragile protein crystals can potentially be damaged, both from physical and environmental shock. To circumvent these challenges an X-ray transparent microfluidic device architecture was developed to couple the benefits of scale, integration, and precise fluid control with the ability to perform in situ X-ray analysis (Chapter 5). This approach was validated successfully by crystallization and subsequent on-chip analysis of the soluble proteins lysozyme, thaumatin, and ribonuclease A and will be extended to microfluidic platforms for in meso membrane protein crystallization. The ability to perform in situ X-ray analysis was shown to provide extremely high quality diffraction data, in part as a result of not being affected by damage due to physical handling of the crystals. As part of the work described in this thesis, a variety of data collection strategies for in situ data analysis were also tested, including merging of small slices of data from a large number of crystals grown on a single chip, to allow for diffraction analysis at biologically relevant temperatures. While such strategies have been applied previously,57,59,61,67 they are potentially challenging when applied via traditional methods due to the need to grow and then mount a large number of crystals with minimal crystal-to-crystal variability. The integrated nature of microfluidic platforms easily enables the generation of a large number of reproducible crystallization trials. This, coupled with in situ analysis capabilities has the potential of being able to acquire high resolution structural data of proteins at biologically relevant conditions for which only small crystals, or crystals which are adversely affected by standard cryocooling techniques, could be obtained (Chapters 5 and 6). While the main focus of protein crystallography is to obtain three-dimensional protein structures, the results of typical experiments provide only a static picture of the protein. The use of polychromatic or Laue X-ray diffraction methods enables the collection of time resolved structural information. These experiments are very sensitive to crystal quality, however, and often suffer from severe radiation damage due to the intense polychromatic X-ray beams. Here, as before, the ability to perform in situ X-ray analysis on many small protein crystals within a microfluidic crystallization platform has the potential to overcome these challenges. An automated method for collecting a "single-shot" of data from a large number of crystals was developed in collaboration with the BioCARS team at the Advanced Photon Source at Argonne National Laboratory (Chapter 6). The work described in this thesis shows that, even more so than for traditional structure determination efforts, the ability to grow and analyze a large number of high quality crystals is critical to enable time resolved structural studies of novel proteins. In addition to enabling X-ray crystallography experiments, the development of X-ray transparent microfluidic platforms also has tremendous potential to answer other scientific questions, such as unraveling the mechanism of in meso crystallization. For instance, the lipidic mesophases utilized during in meso membrane protein crystallization can be characterized by small angle X-ray diffraction analysis. Coupling in situ analysis with microfluidic platforms capable of preparing these difficult mesophase samples at very small volumes has tremendous potential to enable the high throughput analysis of these systems on a scale that is not reasonably achievable using conventional sample preparation strategies (Chapter 7). In collaboration with the LS-CAT team at the Advanced Photon Source, an experimental station for small angle X-ray analysis coupled with the high quality visualization capabilities needed to target specific microfluidic samples on a highly integrated chip is under development. Characterizing the phase behavior of these mesophase systems and the effects of various additives present in crystallization trials is key for developing an understanding of how in meso crystallization occurs. A long term goal of these studies is to enable the rational design of in meso crystallization experiments so as to avoid or limit the need for high throughput screening efforts. In summary, this thesis describes the development of microfluidic platforms for protein crystallization with in situ analysis capabilities. Coupling the ability to perform in situ analysis with the small scale, fine control, and the high throughput nature of microfluidic platforms has tremendous potential to enable a new generation of crystallographic studies and facilitate the structure determination of important biological targets. The development of platforms for in meso membrane protein crystallization is particularly significant because they enable the preparation of highly viscous mixtures at a previously unachievable scale. Work in these areas is ongoing and has tremendous potential to improve not only current the methods of protein crystallization and crystallography, but also to enhance our knowledge of the structure and function of proteins which could have a significant scientific and medical impact on society as a whole. The microfluidic technology described in this thesis has the potential to significantly advance our understanding of the structure and function of membrane proteins, thereby aiding the elucidation of human biology, the development of pharmaceuticals with fewer side effects for a wide range of diseases. References (1) Quick, M.; Javitch, J. A. P Natl Acad Sci USA 2007, 104, 3603. (2) Trubetskoy, V. S.; Burke, T. J. Am Lab 2005, 37, 19. (3) Pecina, P.; Houstkova, H.; Hansikova, H.; Zeman, J.; Houstek, J. Physiol Res 2004, 53, S213. (4) Arinaminpathy, Y.; Khurana, E.; Engelman, D. M.; Gerstein, M. B. Drug Discovery Today 2009, 14, 1130. (5) Overington, J. P.; Al-Lazikani, B.; Hopkins, A. L. Nat Rev Drug Discov 2006, 5, 993. (6) Dauter, Z.; Lamzin, V. S.; Wilson, K. S. Current Opinion in Structural Biology 1997, 7, 681. (7) Hansen, C.; Quake, S. R. Current Opinion in Structural Biology 2003, 13, 538. (8) Govada, L.; Carpenter, L.; da Fonseca, P. C. A.; Helliwell, J. R.; Rizkallah, P.; Flashman, E.; Chayen, N. E.; Redwood, C.; Squire, J. M. J Mol Biol 2008, 378, 387. (9) Hansen, C. L.; Skordalakes, E.; Berger, J. M.; Quake, S. R. P Natl Acad Sci USA 2002, 99, 16531. (10) Leng, J.; Salmon, J.-B. Lab Chip 2009, 9, 24. (11) Zheng, B.; Gerdts, C. J.; Ismagilov, R. F. Current Opinion in Structural Biology 2005, 15, 548. (12) Lorber, B.; Delucas, L. J.; Bishop, J. B. J Cryst Growth 1991, 110, 103. (13) Talreja, S.; Perry, S. L.; Guha, S.; Bhamidi, V.; Zukoski, C. F.; Kenis, P. J. A. The Journal of Physical Chemistry B 2010, 114, 4432. (14) Chayen, N. E. Current Opinion in Structural Biology 2004, 14, 577. (15) He, G. W.; Bhamidi, V.; Tan, R. B. H.; Kenis, P. J. A.; Zukoski, C. F. Cryst Growth Des 2006, 6, 1175. (16) Zheng, B.; Tice, J. D.; Roach, L. S.; Ismagilov, R. F. Angew Chem Int Edit 2004, 43, 2508. (17) Li, L.; Mustafi, D.; Fu, Q.; Tereshko, V.; Chen, D. L. L.; Tice, J. D.; Ismagilov, R. F. P Natl Acad Sci USA 2006, 103, 19243. (18) Song, H.; Chen, D. L.; Ismagilov, R. F. Angew Chem Int Edit 2006, 45, 7336. (19) van der Woerd, M.; Ferree, D.; Pusey, M. Journal of Structural Biology 2003, 142, 180. (20) Ng, J. D.; Gavira, J. A.; Garcia-Ruiz, J. M. Journal of Structural Biology 2003, 142, 218. (21) Talreja, S.; Kenis, P. J. A.; Zukoski, C. F. Langmuir 2007, 23, 4516. (22) Hansen, C. L.; Quake, S. R.; Berger, J. M. US, 2007. (23) Newman, J.; Fazio, V. J.; Lawson, B.; Peat, T. S. Cryst Growth Des 2010, 10, 2785. (24) Newman, J.; Xu, J.; Willis, M. C. Acta Crystallographica Section D 2007, 63, 826. (25) Collingsworth, P. D.; Bray, T. L.; Christopher, G. K. J Cryst Growth 2000, 219, 283. (26) Durbin, S. D.; Feher, G. Annu Rev Phys Chem 1996, 47, 171. (27) Talreja, S.; Kim, D. Y.; Mirarefi, A. Y.; Zukoski, C. F.; Kenis, P. J. A. J Appl Crystallogr 2005, 38, 988. (28) Yoshizaki, I.; Nakamura, H.; Sato, T.; Igarashi, N.; Komatsu, H.; Yoda, S. J Cryst Growth 2002, 237, 295. (29) Anderson, M. J.; Hansen, C. L.; Quake, S. R. P Natl Acad Sci USA 2006, 103, 16746. (30) Hansen, C. L.; Sommer, M. O. A.; Quake, S. R. P Natl Acad Sci USA 2004, 101, 14431. (31) Lounaci, M.; Rigolet, P.; Abraham, C.; Le Berre, M.; Chen, Y. Microelectron Eng 2007, 84, 1758. (32) Zheng, B.; Roach, L. S.; Ismagilov, R. F. J Am Chem Soc 2003, 125, 11170. (33) Zhou, X.; Lau, L.; Lam, W. W. L.; Au, S. W. N.; Zheng, B. Anal. Chem. 2007. (34) Cherezov, V.; Caffrey, M. J Appl Crystallogr 2003, 36, 1372. (35) Qutub, Y.; Reviakine, I.; Maxwell, C.; Navarro, J.; Landau, E. M.; Vekilov, P. G. J Mol Biol 2004, 343, 1243. (36) Rummel, G.; Hardmeyer, A.; Widmer, C.; Chiu, M. L.; Nollert, P.; Locher, K. P.; Pedruzzi, I.; Landau, E. M.; Rosenbusch, J. P. Journal of Structural Biology 1998, 121, 82. (37) Gavira, J. A.; Toh, D.; Lopez-Jaramillo, J.; Garcia-Ruiz, J. M.; Ng, J. D. Acta Crystallogr D 2002, 58, 1147. (38) Stevens, R. C. Current Opinion in Structural Biology 2000, 10, 558. (39) Baker, M. Nat Methods 2010, 7, 429. (40) McPherson, A. In Current Topics in Membranes, Volume 63; Volume 63 ed.; DeLucas, L., Ed.; Academic Press: 2009, p 5. (41) Gabrielsen, M.; Gardiner, A. T.; Fromme, P.; Cogdell, R. J. In Current Topics in Membranes, Volume 63; Volume 63 ed.; DeLucas, L., Ed.; Academic Press: 2009, p 127. (42) Page, R. In Methods in Molecular Biology: Structural Proteomics - High Throughput Methods; Kobe, B., Guss, M., Huber, T., Eds.; Humana Press: Totowa, NJ, 2008; Vol. 426, p 345. (43) Caffrey, M. Ann Rev Biophys 2009, 38, 29. (44) Doerr, A. Nat Methods 2006, 3, 244. (45) Brostromer, E.; Nan, J.; Li, L.-F.; Su, X.-D. Biochemical and Biophysical Research Communications 2009, 386, 634. (46) Li, G.; Chen, Q.; Li, J.; Hu, X.; Zhao, J. Anal Chem 2010, 82, 4362. (47) Jia, Y.; Liu, X.-Y. The Journal of Physical Chemistry B 2006, 110, 6949. (48) RCSB Protein Data Bank. http://www.rcsb.org/ (July 11, 2010). (49) Membrane Proteins of Known 3D Structure. http://blanco.biomol.uci.edu/Membrane_Proteins_xtal.html (July 11, 2010). (50) Michel, H. Trends Biochem Sci 1983, 8, 56. (51) Rosenbusch, J. P. Journal of Structural Biology 1990, 104, 134. (52) Garavito, R. M.; Picot, D. Methods 1990, 1, 57. (53) Kulkarni, C. V. 2010; Vol. 12, p 237. (54) Landau, E. M.; Rosenbusch, J. P. P Natl Acad Sci USA 1996, 93, 14532. (55) Pebay-Peyroula, E.; Rummel, G.; Rosenbusch, J. P.; Landau, E. M. Science 1997, 277, 1676. (56) Cherezov, V.; Liu, W.; Derrick, J. P.; Luan, B.; Aksimentiev, A.; Katritch, V.; Caffrey, M. Proteins: Structure, Function, and Bioinformatics 2008, 71, 24. (57) Cherezov, V.; Rosenbaum, D. M.; Hanson, M. A.; Rasmussen, S. G. F.; Thian, F. S.; Kobilka, T. S.; Choi, H. J.; Kuhn, P.; Weis, W. I.; Kobilka, B. K.; Stevens, R. C. Science 2007, 318, 1258. (58) Cherezov, V.; Yamashita, E.; Liu, W.; Zhalnina, M.; Cramer, W. A.; Caffrey, M. J Mol Biol 2006, 364, 716. (59) Jaakola, V. P.; Griffith, M. T.; Hanson, M. A.; Cherezov, V.; Chien, E. Y. T.; Lane, J. R.; IJzerman, A. P.; Stevens, R. C. Science 2008, 322, 1211. (60) Rosenbaum, D. M.; Cherezov, V.; Hanson, M. A.; Rasmussen, S. G. F.; Thian, F. S.; Kobilka, T. S.; Choi, H. J.; Yao, X. J.; Weis, W. I.; Stevens, R. C.; Kobilka, B. K. Science 2007, 318, 1266. (61) Wacker, D.; Fenalti, G.; Brown, M. A.; Katritch, V.; Abagyan, R.; Cherezov, V.; Stevens, R. C. J Am Chem Soc 2010, 132, 11443. (62) Höfer, N.; Aragão, D.; Caffrey, M. Biophys J 2010, 99, L23. (63) Li, L.; Ismagilov, R. F. Ann Rev Biophys 2010. (64) Pal, R.; Yang, M.; Lin, R.; Johnson, B. N.; Srivastava, N.; Razzacki, S. Z.; Chomistek, K. J.; Heldsinger, D. C.; Haque, R. M.; Ugaz, V. M.; Thwar, P. K.; Chen, Z.; Alfano, K.; Yim, M. B.; Krishnan, M.; Fuller, A. O.; Larson, R. G.; Burke, D. T.; Burns, M. A. Lab Chip 2005, 5, 1024. (65) Jayashree, R. S.; Gancs, L.; Choban, E. R.; Primak, A.; Natarajan, D.; Markoski, L. J.; Kenis, P. J. A. J Am Chem Soc 2005, 127, 16758. (66) Wootton, R. C. R.; deMello, A. J. Chem Commun 2004, 266. (67) McPherson, A. J Appl Crystallogr 2000, 33, 397.

Collimation of deuterium / 3-helium fusion products for advanced spacecraft propulsion and power

Current space exploration has transpired through the use of chemical rockets, and they have served us well, but they have their limitations. Exploration of the outer solar system, Jupiter and beyond will most likely require a new generation of propulsion system. One potential technology class to provide spacecraft propulsion and power systems involve thermonuclear fusion plasma systems. In this class it is well accepted that d-He3 fusion is the most promising of the fuel candidates for spacecraft applications as the 14.7 MeV protons carry up to 80% of the total fusion power while ‘s have energies less than 4 MeV. The other minor fusion products from secondary d-d reactions consisting of 3He, n, p, and 3H also have energies less than 4 MeV. Furthermore there are two main fusion subsets namely, Magnetic Confinement Fusion devices and Inertial Electrostatic Confinement (or IEC) Fusion devices. Magnetic Confinement Fusion devices are characterized by complex geometries and prohibitive structural mass compromising spacecraft use at this stage of exploration. While generating energy from a lightweight and reliable fusion source is important, another critical issue is harnessing this energy into usable power and/or propulsion. IEC fusion is a method of fusion plasma confinement that uses a series of biased electrodes that accelerate a uniform spherical beam of ions into a hollow cathode typically comprised of a gridded structure with high transparency. The inertia of the imploding ion beam compresses the ions at the center of the cathode increasing the density to the point where fusion occurs. Since the velocity distributions of fusion particles in an IEC are essentially isotropic and carry no net momentum, a means of redirecting the velocity of the particles is necessary to efficiently extract energy and provide power or create thrust. There are classes of advanced fuel fusion reactions where direct-energy conversion based on electrostatically-biased collector plates is impossible due to potential limits, material structure limitations, and IEC geometry. Thermal conversion systems are also inefficient for this application. A method of converting the isotropic IEC into a collimated flow of fusion products solves these issues and allows direct energy conversion. An efficient traveling wave direct energy converter has been proposed and studied by Momota , Shu and further studied by evaluated with numerical simulations by Ishikawa and others. One of the conventional methods of collimating charged particles is to surround the particle source with an applied magnetic channel. Charged particles are trapped and move along the lines of flux. By introducing expanding lines of force gradually along the magnetic channel, the velocity component perpendicular to the lines of force is transferred to the parallel one. However, efficient operation of the IEC requires a null magnetic field at the core of the device. In order to achieve this, Momota and Miley have proposed a pair of magnetic coils anti-parallel to the magnetic channel creating a null hexapole magnetic field region necessary for the IEC fusion core. Numerically, collimation of 300 eV electrons without a stabilization coil was demonstrated to approach 95% at a profile corresponding to Vsolenoid = 20.0V, Ifloating = 2.78A, Isolenoid = 4.05A while collimation of electrons with stabilization coil present was demonstrated to reach 69% at a profile corresponding to Vsolenoid = 7.0V, Istab = 1.1A, Ifloating = 1.1A, Isolenoid = 1.45A. Experimentally, collimation of electrons with stabilization coil present was demonstrated experimentally to be 35% at 100 eV and reach a peak of 39.6% at 50eV with a profile corresponding to Vsolenoid = 7.0V, Istab = 1.1A, Ifloating = 1.1A, Isolenoid = 1.45A and collimation of 300 eV electrons without a stabilization coil was demonstrated to approach 49% at a profile corresponding to Vsolenoid = 20.0V, Ifloating = 2.78A, Isolenoid = 4.05A 6.4% of the 300eV electrons’ initial velocity is directed to the collector plates. The remaining electrons are trapped by the collimator’s magnetic field. These particles oscillate around the null field region several hundred times and eventually escape to the collector plates. At a solenoid voltage profile of 7 Volts, 100 eV electrons are collimated with wall and perpendicular component losses of 31%. Increasing the electron energy beyond 100 eV increases the wall losses by 25% at 300 eV. Ultimately it was determined that a field strength deriving from 9.5 MAT/m would be required to collimate 14.7 MeV fusion protons from d-3He fueled IEC fusion core. The concept of the proton collimator has been proven to be effective to transform an isotropic source into a collimated flow of particles ripe for direct energy conversion.

Numerical simulation of strain-adaptive bone remodelling in the ankle joint

Background: The use of artificial endoprostheses has become a routine procedure for knee and hip joints while ankle arthritis has traditionally been treated by means of arthrodesis. Due to its advantages, the implantation of endoprostheses is constantly increasing. While finite element analyses (FEA) of strain-adaptive bone remodelling have been carried out for the hip joint in previous studies, to our knowledge there are no investigations that have considered remodelling processes of the ankle joint. In order to evaluate and optimise new generation implants of the ankle joint, as well as to gain additional knowledge regarding the biomechanics, strain-adaptive bone remodelling has been calculated separately for the tibia and the talus after providing them with an implant. Methods: FE models of the bone-implant assembly for both the tibia and the talus have been developed. Bone characteristics such as the density distribution have been applied corresponding to CT scans. A force of 5,200 N, which corresponds to the compression force during normal walking of a person with a weight of 100 kg according to Stauffer et al., has been used in the simulation. The bone adaptation law, previously developed by our research team, has been used for the calculation of the remodelling processes. Results: A total bone mass loss of 2% in the tibia and 13% in the talus was calculated. The greater decline of density in the talus is due to its smaller size compared to the relatively large implant dimensions causing remodelling processes in the whole bone tissue. In the tibia, bone remodelling processes are only calculated in areas adjacent to the implant. Thus, a smaller bone mass loss than in the talus can be expected. There is a high agreement between the simulation results in the distal tibia and the literature regarding. Conclusions: In this study, strain-adaptive bone remodelling processes are simulated using the FE method. The results contribute to a better understanding of the biomechanical behaviour of the ankle joint and hence are useful for the optimisation of the implant geometry in the future.

Heat transfer performance investigation of nanofluids flow in pipe

Different types of base fluids, such as water, engine oil, kerosene, ethanol, methanol, ethylene glycol etc. are usually used to increase the heat transfer performance in many engineering applications. But these conventional heat transfer fluids have often several limitations. One of those major limitations is that the thermal conductivity of each of these base fluids is very low and this results a lower heat transfer rate in thermal engineering systems. Such limitation also affects the performance of different equipments used in different heat transfer process industries. To overcome such an important drawback, researchers over the years have considered a new generation heat transfer fluid, simply known as nanofluid with higher thermal conductivity. This new generation heat transfer fluid is a mixture of nanometre-size particles and different base fluids. Different researchers suggest that adding spherical or cylindrical shape of uniform/non-uniform nanoparticles into a base fluid can remarkably increase the thermal conductivity of nanofluid. Such augmentation of thermal conductivity could play a more significant role in enhancing the heat transfer rate than that of the base fluid. Nanoparticles diameters used in nanofluid are usually considered to be less than or equal to 100 nm and the nanoparticles concentration usually varies from 5% to 10%. Different researchers mentioned that the smaller nanoparticles concentration with size diameter of 100 nm could enhance the heat transfer rate more significantly compared to that of base fluids. But it is not obvious what effect it will have on the heat transfer performance when nanofluids contain small size nanoparticles of less than 100 nm with different concentrations. Besides, the effect of static and moving nanoparticles on the heat transfer of nanofluid is not known too. The idea of moving nanoparticles brings the effect of Brownian motion of nanoparticles on the heat transfer. The aim of this work is, therefore, to investigate the heat transfer performance of nanofluid using a combination of smaller size of nanoparticles with different concentrations considering the Brownian motion of nanoparticles. A horizontal pipe has been considered as a physical system within which the above mentioned nanofluid performances are investigated under transition to turbulent flow conditions. Three different types of numerical models, such as single phase model, Eulerian-Eulerian multi-phase mixture model and Eulerian-Lagrangian discrete phase model have been used while investigating the performance of nanofluids. The most commonly used model is single phase model which is based on the assumption that nanofluids behave like a conventional fluid. The other two models are used when the interaction between solid and fluid particles is considered. However, two different phases, such as fluid and solid phases is also considered in the Eulerian-Eulerian multi-phase mixture model. Thus, these phases create a fluid-solid mixture. But, two phases in the Eulerian-Lagrangian discrete phase model are independent. One of them is a solid phase and the other one is a fluid phase. In addition, RANS (Reynolds Average Navier Stokes) based Standard κ-ω and SST κ-ω transitional models have been used for the simulation of transitional flow. While the RANS based Standard κ-ϵ, Realizable κ-ϵ and RNG κ-ϵ turbulent models are used for the simulation of turbulent flow. Hydrodynamic as well as temperature behaviour of transition to turbulent flows of nanofluids through the horizontal pipe is studied under a uniform heat flux boundary condition applied to the wall with temperature dependent thermo-physical properties for both water and nanofluids. Numerical results characterising the performances of velocity and temperature fields are presented in terms of velocity and temperature contours, turbulent kinetic energy contours, surface temperature, local and average Nusselt numbers, Darcy friction factor, thermal performance factor and total entropy generation. New correlations are also proposed for the calculation of average Nusselt number for both the single and multi-phase models. Result reveals that the combination of small size of nanoparticles and higher nanoparticles concentrations with the Brownian motion of nanoparticles shows higher heat transfer enhancement and thermal performance factor than those of water. Literature suggests that the use of nanofluids flow in an inclined pipe at transition to turbulent regimes has been ignored despite its significance in real-life applications. Therefore, a particular investigation has been carried out in this thesis with a view to understand the heat transfer behaviour and performance of an inclined pipe under transition flow condition. It is found that the heat transfer rate decreases with the increase of a pipe inclination angle. Also, a higher heat transfer rate is found for a horizontal pipe under forced convection than that of an inclined pipe under mixed convection.

Una aproximación para la descripción semántica de requisitos para categorización docentes de investigadores Ecuatorianos

La nueva generación de la Web, la Web Semántica, plantea potenciales oportunidades para dotar de significado a los contenidos Web. Las ontologías constituyen una de las principales herramientas para especificar explícitamente los conceptos de un dominio concreto, sus propiedades y sus relaciones; de manera que la información se publique en formatos que sean inteligibles automáticamente por agentes máquinas que pueden localizar y gestionar de forma precisa la información. En este trabajo se presenta un marco de trabajo para una red de ontologías para representar conceptos, atributos, operaciones y restricciones, en relación a los ítems curriculares que se usan en procesos nacionales de categorización de docentes universitarios ecuatorianos. En una primera parte se muestra el contexto del dominio, trabajos relacionados, luego se describe el proceso seguido, la abstracción del modelo ontológico y finalmente se presenta una ontología. Es una ontología de dominio debido a que proporciona el significado de los conceptos y sus relaciones dentro del dominio de ítems curriculares producidos por docentes universitarios, que son requisitos de los proceso de categorización docente universitaria en Ecuador.

A tecnologia no ensino da interpretação

Tese de Mestrado em Tradução e Interpretação Especializadas Área Científica de Línguas e Culturas

A framework for abstraction and virtualization of sensors in mobile context-aware computing

110 p.

Comportamento organizacional: XXI temas e debates para o séc. XXI

Este artigo representa uma tentativa ensaística de elencar 21 temas que, porventura, marcarão o interesse e a investigação no seio da disciplina do comportamento organizacional. Sem pretensões de exaustividade e visando descortinar janelas de oportunidade para investigação, os autores fazem um breve retrato de uma grande diversidade de temas (e.g., ética e responsabilidade social, conciliação do trabalho com a vida familiar, teletrabalho e organizações virtuais, contratos psicológicos da «nova geração», organizações baseadas no conhecimento, globalização e transculturalização, organizações autentizóticas, dignidade humana no trabalho), procurando também gizar as pistas dinâmicas que cada um deles poderá tomar. O panorama traçado procura reflectir as mudanças que as envolventes organizacionais têm vindo a concitar, projectando sobre as organizações e os respectivos decisores um vasto catálogo de desafios, questionamentos e oportunidades – factos e possíveis desenvolvimentos a que os investigadores e estudiosos do CO não devem ficar alheios.

Application of an online-biomass sensor in an optical multisensory platform prototype for growth monitoring of biotechnical relevant microorganism and cell lines in single-use shake flasks

In the context of this work we evaluated a multisensory, noninvasive prototype platform for shake flask cultivations by monitoring three basic parameters (pH, pO2 and biomass). The focus lies on the evaluation of the biomass sensor based on backward light scattering. The application spectrum was expanded to four new organisms in addition to E. coli K12 and S. cerevisiae [1]. It could be shown that the sensor is appropriate for a wide range of standard microorganisms, e.g., L. zeae, K. pastoris, A. niger and CHO-K1. The biomass sensor signal could successfully be correlated and calibrated with well-known measurement methods like OD600, cell dry weight (CDW) and cell concentration. Logarithmic and Bleasdale-Nelder derived functions were adequate for data fitting. Measurements at low cell concentrations proved to be critical in terms of a high signal to noise ratio, but the integration of a custom made light shade in the shake flask improved these measurements significantly. This sensor based measurement method has a high potential to initiate a new generation of online bioprocess monitoring. Metabolic studies will particularly benefit from the multisensory data acquisition. The sensor is already used in labscale experiments for shake flask cultivations.