Portrycket är en viktig parameter för att bestämma jordens egenskaper, såsom dränering, permeabilitet och stabilitet (då portrycket har en påverkan på den effektiva spänningen i jorden). Portrycket kan mätas med portrycksmätare men det kan även mätas under ett Cone penetrating test (CPT) med ett s.k. dissipationstest. Fördelar med ett dissipationstest jämfört med traditionell portrycksmätning skulle vara att det skulle spara tid och pengar, då man slipper trycka ner portrycksmätare och sedan vänta på att få portrycket ifrån dem, istället kan portrycket mätas under sondering med CPT.Detta självständiga arbete har som syfte att jämföra portrycksmätningar mellan portrycksmätning med BAT-spets och dissipationstest under CPT-sondering för att se hur bra mätvärden dissipationstester ger och om de eventuellt kan ersätta portrycksmätare. Fältförsöken av metoderna skedde i Uppsalalera, på en tomt i Kungsängen i Uppsala.Två stationer med BAT-spetsar på 5 meter, 7,5 meter och 10 meters djup sattes ner i leran. Sondering med CPT genomfördes sedan, där borren stoppades på samma djup som BAT-spetsarna. CPT:n stoppades på dessa djup i drygt 24 timmar, för att tillåta det generade portrycket som skapades när borren trycks ner i leran att skingras åt sidan. Jämviktsportrycket kommer vara det portryck som finns kvar efter att det generade portrycket har försvunnit. Portrycken från de två olika metoderna jämfördes sedan för att se hur nära dissipationstestet kommer värdena från portrycksmätningen med BAT-spetsarna.Resultatet av dissipationstesterna blev att inga av dem nådde referensvärdena från BAT-spetsarna efter 24 timmar. Beroende på användningsklass ligger dissipationstesterna inom den tillåtna minsta noggrannheten. Dissipationstest är antagligen inte så praktiskt tillämpbart i jordar med låg permeabilitet. / The pore pressure is an important parameter for determining the properties of thesoil, such as drainage, permeability and stability (since the pore pressure has aneffect on the effective stress in the soil). The pore pressure can be measured withpore pressure gauges but it can also be measured during a Cone penetration test(CPT) with a dissipation test. Advantages of a dissipation test compared tomeasurement with traditional pore pressure gauges would be that it would save timeand money, since you don’t have to press down pore pressure gauges and then waitto get the pore pressure from them, instead the pore pressure can be measuredduring probing with CPT.The purpose of this project is to compare pore pressure measurements betweenpore pressure measurements with BAT-tips and dissipation test during CPT probing,to see how good measured values the dissipation tests will provide and if theyeventually can supersede pore pressure gauges for pore pressure measurements.The field tests of the methods were done in Uppsala clay, on a site in Kungsängen inUppsala.Two stations with BAT-tips at 5 meters, 7.5 meters and 10 meters depth wereinstalled in the clay. Probing with CPT was then carried out, by stopping the CPT atthe same depth as the BAT-tips. Measurements with the CPT were done at thesedepths for just over 24 hours, to allow the generated excess pore pressure createdwhen the cone is pushed into the clay to disperse to the sides. The equilibrium porepressure is the pore pressure that remains after the generated pore pressure hasdissipated. The pore pressure from the two different methods was then compared tosee how close the dissipation test results were to the values from the pore pressuremeasurements with the BAT tips.The result of the dissipation tests was that none of them reached the referencevalues from the BAT-tips after 24 hours. Depending on the chosen application class,the dissipation tests are within the permitted minimum accuracy. Dissipation tests areprobably not practically applicable to soils with low permeability.

Conselho Nacional de Desenvolvimento CientÃfico e TecnolÃgico / IntroduÃÃo: O cloridrato de irinotecano (CPT-11) à um inibidor da topoisomerase I, clinicamente efetivo no tratamento de vÃrios tipos de cÃncer. Apesar da mucosite intestinal (MI) acompanhada de severa diarrÃia ser o efeito colateral mais limitante do uso terapÃutico do CPT-11, os exatos mecanismos que levam a estes efeitos nÃo sÃo estabelecidos. Objetivo: avaliar o envolvimento de mediadores inflamatÃrios (citocinas, Ãxido nÃtrico â NO e prostaglandinas â PGs) na patogÃnese dos eventos que acompanham a MI induzida pelo CPT-11; e estudar o efeito de inibidores da sÃntese e liberaÃÃo de citocinas, como pentoxifilina (PTX) e talidomida (TLD), e de um inibidor seletivo da ciclooxigenase-2 (COX-2), o celecoxibe (CLX), na lesÃo intestinal induzida pelo CPT-11. Material e MÃtodos: camundongos Swiss, machos, foram tratados durante quatro dias consecutivos com CPT-11 (50, 75 e 100 mg/kg, i.p.) ou veÃculo (0,5 mL, i.p.), a fim de se obter a melhor dose capaz de induzir injÃrias consistentes com o mÃnimo de letalidade. Os animais foram tratados com PTX (1,7, 5 e 15 mg/kg, s.c.), TLD (15, 30, 60 mg/kg, s.c), CLX (3, 10, 30 mg/kg, gavagem) ou veÃculo (0,5 mL, s.c. ou gavagem), um dia antes da primeira administraÃÃo do CPT-11 (75 mg/kg), e diariamente, atà o sacrifÃcio, no quinto ou sÃtimo dia. Os seguintes parÃmetros foram avaliados: diarrÃia, variaÃÃo de massa corpÃrea, leucograma, sobrevida, anÃlise histopatolÃgica, atividade de mieloperoxidase (MPO), dosagem de citocinas (TNF-α, IL-1β e KC) por ELISA e imunohistoquÃmica para TNF-α, IL-1β, iNOS e COX-2 nas mucosas duodenais. Resultados: CPT-11 induziu diarrÃia significante, acompanhada de perda acentuada de massa corpÃrea, leucopenia e reduÃÃo da sobrevida. As alteraÃÃes histopatolÃgicas intestinais induzidas pelo CPT-11 caracterizaram-se pela presenÃa de infiltrado inflamatÃrio nas cÃlulas da lÃmina prÃpria, perda da arquitetura das criptas e achatamento dos vilos. Observou-se ainda, aumento intestinal na atividade de MPO e dos nÃveis de TNF-α, IL-1β e KC, alÃm do aumento significativo na marcaÃÃo imunohistoquÃmica para TNF-α, IL-1β, iNOS e COX-2. O tratamento com PTX inibiu a diarrÃia tardia, reduziu as alteraÃÃes histopatolÃgicas, a atividade de MPO, e os nÃveis de TNF-α, IL-1β e KC, assim como a marcaÃÃo imunohistoquÃmica para TNF-α, IL-1β e iNOS na mucosa duodenal, entretanto, nÃo preveniu significativamente a perda de massa corpÃrea, a leucopenia e tampouco a mortalidade dos animais. O tratamento com TLD reduziu as lesÃes histopatolÃgicas induzidas pelo CPT-11 na mucosa intestinal, os nÃveis intestinais de MPO e TNF-α, bem como a marcaÃÃo imunohistoquÃmica de TNF-α, mas nÃo foi capaz de prevenir a diarrÃia, a perda de massa corpÃrea, a leucopenia e a sobrevida. O tratamento com CLX nÃo foi capaz de reduzir os parÃmetros inflamatÃrios e sistÃmicos observados nos animais tratados com CPT-11. ConclusÃo: Estes resultados sugerem o envolvimento de TNF-α, IL-1β, KC, NO e PGs na patogÃnese da MI induzida pelo CPT-11. PTX e TLD preveniram significativamente as alteraÃÃes histolÃgicas e inflamatÃrias induzidas pelo CPT-11, entretanto, somente PTX foi capaz de inibir o curso da diarrÃia / Introduction: Irinotecan (CPT-11) is an inhibitor of DNA topoisomerase I and clinically effective against several cancers. A major toxic effect of CPT-11 is delayed diarrhea; however, the exact mechanism by which the drug induces diarrhea has not been established. Purpose: The aim of the present study was to elucidate the involvement of cytokines (TNF-α, IL-1β and KC), nitric oxide (NO) and prostaglandins (PGs) in the pathogenesis of CPT-11-induced mucositis and the effects of the cytokine production inhibitors, pentoxifylline (PTX) and thalidomide (TLD), as well as the effects of the selective cyclooxygenase (COX-2) inhibitor, celecoxib (CLX), in the CPT-11 induced intestinal mucositis, in mice. Materials and methods: the animals were treated with CPT-11 (50, 75 or 100 mg/kg, i.p.) or vehicle (0,5 ml, i.p.) daily for four days, in order to investigate the best dose able to induce intestinal mucositis without important mortality. In another set of experiments, the animals received PTX (1.7, 5, 15 mg/kg, s.c.), TLD (15, 30, 60 mg/kg, s.c.), CLX (3, 10, 30 mg/kg, oral gavage) or vehicle (0,5 ml, s.c. or oral gavage) one day before the 1st administration of CPT-11 (75 mg/kg; i.p.) and daily until the sacrifice, on the 5th or 7th day. The systemic parameters evaluated were: diarrhea, body mass variation, survival curve and leucogram. In addition, it was also performed histological analysis, myeloperoxidase (MPO) activity assay, duodenum levels of TNF-α, IL-1β and KC by ELISA and immunohistochemistry for TNF-α, IL-1β, iNOS and COX-2 in the duodenal segments. Results: CPT-11 induced an important diarrhea, weight loss, leucopenia and mortality increase. It was also observed histopathological changes, such as shortened villi, loss of the crypt architecture and inflammatory cells infiltration, observed in the lamina propria, as well as, an increase in MPO activity, TNF-α, IL-1β and KC tissue levels and a marked immuno-staining for TNF-α, IL-1β, iNOS and COX-2. The treatment with PTX inhibited the delayed diarrhea and reduced the following parameters: histopathological alterations, MPO activity, tissue levels of TNF-α, IL-1β and KC, and the immuno-staining for TNF-α, IL-1β and iNOS, however, did not prevent leucopenia, weight loss and mortality. TLD significantly reduced all the inflammatory parameters evaluated, but was not able to prevent diarrhea, leucopenia, weight loss and mortality. On the other hand, CLX did not inhibit the inflammatory nor the systemic alterations induced by CPT-11. Conclusion: These results suggest an important role of TNF-α, IL-1β, KC, NO and PGs in the pathogenesis of intestinal mucositis induced by CPT-11. PTX and TLD showed a protector effect in intestinal structures, however, only PTX reduced the severity of CPT-11-induced diarrhea

Background: The Mountain Home Veterans Affairs (VA) Medical Center has been diagnosing and treating veterans with benign paroxysmal positional vertigo (BPPV) for almost 2 decades. The clinic protocol includes a 2-week follow-up visit to determine the treatment outcome of the canalith repositioning treatment (CRT). To date, the characteristics of BPPV and treatment efficacy have not been reported in a cohort of veterans with BPPV. Purpose: To determine the prevalence and characteristics of veterans diagnosed with BPPV in a Veterans Affairs Medical Center Audiology Clinic and to examine treatment outcomes. Research Design: Retrospective chart review. Study Sample: A total of 102 veterans who tested positive for BPPV in the Vestibular Clinic at the Mountain Home VA Medical Center from March 2010 to August 2011. Results: In 102 veterans who were diagnosed with BPPV, the posterior semicircular canal was most often involved (75%), motion-provoked vertigo was the most common symptom (84%), and the majority (43%) were diagnosed with BPPV in their sixth decade. The prevalence of BPPV in the Audiology Vestibular Clinic was 15.6%. Forty-one percent of veterans reported a symptom onset within 12 months of treatment for BPPV; however, 36% reported their symptoms began > 36 months prior to treatment. CRT was effective (negative Dix–Hallpike/roll test) in most veterans (86%) following 1 treatment appointment (M = 1.6), but more than half reported incomplete symptom resolution (residual dizziness) at the follow-up appointment. Eighteen percent of veterans experienced a recurrence (M = 1.8 years; SD = 1.7 years). Conclusions: The characteristics and treatment outcomes of BPPV in our veteran cohort was similar to what has been reported in the general population. Future work should focus on improving the timeliness of evaluation and treatment of BPPV and examining the time course and management of residual dizziness.

The crystal structures of two thermostable carboxylesterase Est30 and Est55 from Geobacillus stearothermophilus were determined to help understand their functions and applications in industry or medicine. The crystal structure of Est30 was determined at 1.63 Å resolution by the multiple anomalous dispersion method. The two-domain Est30 structure showed a large domain with a modified alpha/beta hydrolase core including a seven, rather than an eight-stranded beta sheet, and a smaller cap domain comprising three alpha helices. A 100 Da tetrahedral ligand, propyl acetate, was observed to be covalently bound to the side chain of Ser94 in the catalytic triad. This ligand complex represents the first tetrahedral intermediate in the reaction mechanism. Therefore, this Est30 crystal structure will help understand the mode of action of all enzymes in the serine hydrolase superfamily. Est55 is a bacterial homologue of the mammalian carboxylesterases involved in hydrolysis and detoxification of numerous peptides and drugs and in prodrug activation. Est55 crystals were grown at pH 6.2 and pH 6.8 and the structures were determined at resolutions of 2.0 and 1.58 Å respectively. Est55 folds into three domains, a catalytic domain, an α/β domain and a regulatory domain. This structure is in an inactive form; the side chain of His409, one of the catalytic triad residues, is pointing away from the active site. Moreover, the adjacent Cys408 is triply oxidized and lies in the oxyanion hole, which would block the entry of substrate to its binding site. This structure suggested a self-inactivation mechanism, however, Cys408 is not essential for enzyme activity. Mutation of Cys408 showed that hydrophobic side chains at this position were favorable, while polar serine was unfavorable for enzyme activity. Both Est30 and Est55 were shown to hydrolyze the prodrug CPT-11 into the active form SN-38. Therefore, Est30 and Est55 are potential candidates for use with irinotecan in cancer therapy. The catalytic efficiency (kcat/Km) of Est30 is about 10-fold lower than that of Est55. The effects of the Cys408 substitutions on Est55 activity differed for the two substrates, p-NP butyrate and CPT-11. Mutant C408V may provide a more stable form of Est55.

Piles have been used since prehistoric times in areas with weak subsurface conditions either to reinforce existing ground, create new ground for habitation or trade, and support bridges and buildings. Originally piles were composed of timber and driven with drop hammers using very heavy ram weights. As technology improved so did the materials that piles are composed of as well as the equipment itself. Currently, piling is a multibillion dollar a year industry, thus the need to develop more accurate prediction methods can potentially represent a significant savings in cost, material, and man power. Multiple predictive methods have been developed to estimate developed pile capacity. These range from static theoretical formulae based on geotechnical investigation prior to pile driving even occurring using specific pile and hammer types to semi empirically based dynamic formulae used during actual driving operations to more recently developed computer modeling and signal matching programs which are calibrated with site condition during initial geotechnical investigations or test piling to full scale static load tests where piles are loaded to some predetermined value or failure condition. In this thesis, dynamic formulae are used to predict pile capacity from those installed by drop and diesel hammers and are compared to the results from pile load tests, which are taken as the true measure of developed bearing capacity. The dynamic formulae examined are the Engineering News Record (ENR), Gates, Federal Highway Administration (FHWA) modified Gates, Hiley, and Ontario Ministry of Transportation (MTO) modified Hiley formulae. Methods of investigation include calculating pile capacities from the formulae as they are, omitting the factors of safety, revising the formulae with averaged coefficients and conducting multi regression analysis to solve for one or two coefficients simultaneously and revising the dynamic formula to determine if more accurate bearing capacity prediction are possible. To objectively determine which formulae provide the most accurate bearing capacities, the predicted capacities will be compared to results obtained from static pile load tests and simple statistics on the resulting data set will be calculated including regression analysis, standard deviations, coefficients of variation, coefficients of determination, and correlation values.

Physics in the year 2006 is tightly constrained by experiment, observation, and mathematical consistency. The Standard Model provides a remarkably precise de- scription of particle physics, and general relativity is quite successful in describing gravitational phenomena. At the same time, it is clear that a more fundamental theory is needed for several distinct reasons. Here we consider a new approach, which begins with the unusually ambitious point of view that a truly fundamental theory should aspire to explaining the origins of Lorentz invariance, gravity, gauge fields and their symmetry, supersymmetry, fermionic fields, bosonic fields, quantum mechanics and spacetime. The present dissertation is organized so that it starts with the most conventional ideas for extending the Standard Model and ends with a microscopic statistical picture, which is actually the logical starting point of the theory, but which is also the most remote excursion from conventional physics. One motivation for the present work is the fact that a Euclidean path integral in quantum physics is equivalent to a partition function in statistical physics. This suggests that the most fundamental description of nature may be statistical. This dissertation may be regarded as an attempt to see how far one can go with this premise in explaining the observed phenomena, starting with the simplest statistical picture imaginable. It may be that nature is richer than the model assumed here, but the present results are quite suggestive, because, with a set of assumptions that are not unreasonable, one recovers the phenomena listed above. At the end, the present theory leads back to conventional physics, except that Lorentz invariance and supersymmetry are violated at extremely high energy. To be more specific, one obtains local Lorentz invariance (at low energy compared to the Planck scale), an SO(N) unified gauge theory (with N = 10 as the simplest possibility), supersymmetry of Standard Model fermions and their sfermion partners, and other familiar features of standard physics. Like other attempts at superunification, the present theory involves higher dimensions and topological defects.

The static cone penetration tests are quite extensively used for carrying out in-situ geotechnical investigations both for onshore and offshore sites especially where the soil mass is expected to comprise of either soft to medium stiff clays or loose to medium dense sands. The wide use of the cone penetration tests (CPT) in geotechnical engineering has resulted in a great demand for developing necessary correlations between the cone penetration resistance and different engineering properties of soils. The successful interpretation of the cone penetration test data depends mainly on the various empirical correlations which are often derived with the help of a controlled testing in calibration chambers. The calibration chambers have been deployed in various sizes (diameter varying from 0.55 m to 2.10 m) by a number of researchers. It is quite an expensive and time consuming exercise to carry out controlled tests in a large size calibration chamber. The task becomes even much more difficult when a sample comprising of either silt or clay has to be prepared. As a result, most of the reported cone penetration tests in calibration chambers are mainly performed in a sandy material. Taking into account the various difficulties associated with performing tests in large calibration chambers, in the present study, it is attempted to make use of a miniature static cone penetrometer having a diameter of 19.5 mm. This cone was gradually penetrated at a uniform rate in a triaxial cell in which a soil sample of a given material was prepared; the diameter of the cone was intentionally chosen smaller so that the ratio of the diameter of the cell to that of the cone becomes a little larger. Two different diameters of the cells, namely, 91 mm and 140 mm, were used to explore the effect of the ratio of chamber (cell) size to that of the cone size. In addition, the rate of penetration rate was also varied from 0.6 mm/minute to 6.0 mm/minute (the maximum possible rate for the chosen triaxial machine with the larger cell) to examine the effect of the rate of the penetration of the miniature cone on the tip resistance. By using the chosen experimental setup, a large number of static miniature cone penetrometer tests were carried out on four different materials, namely, (i) clean sand, (ii) sand with 15% silt, (iii) sand with 25% silt, and (iv) sand with 15% fly ash. The cone tip resistance for each material was obtained for a wide range of three different relative densities. The effective vertical pressure (σv) for the tests on different samples was varied in between 100 kPa and 300 kPa. The variations of the tip resistance with axial deformation in all the cases were monitored so as to find the magnitude of the ultimate tip resistance. In contrast to the standard cone, the diameter of the piston shaft was intentionally kept a little smaller than that of the cone itself so as to restrict the development of the piston resistance. For each cell (chamber) size, two different sizes of the pistons were used to assess the resistance offered by the penetration of the piston shaft itself. It was noted that the resistance offered by the chosen piston shaft is not very substantial as compared to that of the cone tip itself. Most of the experimental observations noted from the present experiments were similar to those made by the penetration of the standard size cone in a large calibration chamber. The ultimate tip resistance of the cone was found to increase invariably with an increase in the magnitude of σv. An increase in the relative density of the soil mass leads to an increase in the value of qcu. For the same range of relative densities, an addition of fly ash in the sample of sand, leads to a considerable reduction in the magnitude of qcu. Even with the addition of 25% silt, the values of qcu were found to become generally lower as compared to clean sand and sand added with 15% silt. An employment of a larger ratio of the diameter of the cell to that of the miniature cone leads to an increased magnitude of qcu. An increase in the penetration rate from 0.6 mm/min to 6.0 mm/min, was found to cause a little increase in the magnitude of qcu especially for sand added with fly ash and silt. The effect of the penetration rate on the results was found to increase continuously with a reduction in the rate of penetration. At higher penetration rates, in a range closer to those normally employed in the field (20 mm/sec), it is expected that the rate of penetration of the cone will not have any substantial effects on the magnitude of qcu for clean sands. The magnitude of qcu obtained in this thesis at different values of σv for all the cases with the use of the miniature cone were compared with the two widely used correlations in literature. It is found that except for dense sands, in most of the cases, the present experimental data lie generally in between the two correlation curves from literature; for dense sands the measured values of qcu were found to be significantly lower than the chosen correlation curves. It was noted that with the use of the miniature cone penetrated in a given sample prepared in a triaxial cell, it is possible to obtain reasonably an accurate estimate of the tip resistance of the standard cone especially for loose to medium dense states of all the materials. Further, from the analysis of all the tests results, it was noted that approximately a linear correlation between qcu/σv and soil friction angle (φ) for different chosen materials exists provided the dependency of the φ on the stress level is taken into account. As compared to the standard cone penetrometer which is usually employed in the field, the miniature cone used in this study is expected to provide a little conservative estimate, of the tip resistance of the standard static cone penetrometer with reference to the different materials used in this study on account of the facts that (i) there is a reduced area behind the cone, (ii) the ratio of the diameter of the calibration chamber (cell) to that of cone is not very high, (iii) the chosen size of the cone is smaller than the standard cone, and (iv) the chosen penetration rate is much smaller than the standard rate of penetration. Further, in the case of clean sand, an attempt has also been made in this thesis, with the help of a number of direct shear tests at different stress levels, to generate an expression correlating peak friction angle, critical state friction angle, relative density of sand and vertical effective stress. A correlation has been generated with the help of which, the value of peak dilatancy angle can be obtained from the known values of peak friction angle and critical state friction angle. In confirmation with the available information in literature, this exercise on clean sand has clearly indicated that a decrease in the magnitude of vertical effective stress leads to an increase in the values of both peak friction angles and peak dilatancy angles.

Professional research project (Au.D.)--University of South Florida, 2001. / Title from PDF of title page. / Document formatted into pages; contains 29 pages. / Includes bibliographical references. / Text (Electronic thesis) in PDF format. / ABSTRACT: The primary objective of the project was to survey audiologists in clinical practice setting to determine the amount of time taken to perform various audiologic tests using Current Procedural Terminology, (CPT) codes to define these tests and if these CPT codes were felt to be adequate. Audiologists were also asked to respond regarding possible impact and reimbursement changes in their clinical practices related to managed care. Responses of audiologists were analyzed to determine: a) adequacy of CPT codes; b)average time to perform various audiologic tests; c) impact managed care onclinical practice; and d) changes in reimbursement as a result of managed care. / The survey was designed to determine the type of work setting, typical job duty, average monthly caseload and hours per day spent on patient care for each respondent. The survey with a cover letter explaining the purpose was mailed to 93 audiologists in clinical setting in the state of Florida. Five were returned undeliverable, and 39 of the remaining 88 were returned either completed or partially completed. The survey results revealed over 71% of the audiologists felt the current CPT codes were adequate. Time spent performing traditional audiologic tests, such as comprehensive audiometric evaluations and impedance testing, was fairly consistent. / Greater time variability occurred in tests used to determine vestibular function. Over three-quarters of the respondents believed managed care has had a negative impact on their clinical practices, while 11% believe they have been positively impacted. Approximately 82% of the audiologists have had reductions in reimbursement as a result of managed care, while 10% have seen no change and 5% have enjoyed slightly greater reimbursement. / System requirements: World Wide Web browser and PDF reader. / Mode of access: World Wide Web.

This thesis consisted of experiments designed to explore the construct of attention and investigate the disruptive effects of psychotomimetics, with a specific focus on NMDA antagonists. Phencyclidine (PCP) was administered through a variety of treatment regimens in order to to determine the ability of inducing cognitive-specific disruptions in attentional functioning. The hypothesis that sub-chronic exposure to PCP would result in persistent attentional impairment was tested, using the 5-choice serial reaction time task (5-CSRTT). The 5-CSRTT assesses not only visuospatial attention, but also components of impulsivity, compulsivity, speed of processing and motivation. It was determined that an additional task-related intervention that increased the attentional load was required to elucidate attentional impairment following sub-chronic PCP treatment. The ability of rats to perform the modified version of the 5-CSRTT, known as the 5-choice continuous performance test (5C-CPT), was investigated. The 5C-CPT was implemented to provide a task that may have greater analogy to the human CPT, than the original 5-CSRTT. The consequence of dopaminergic D1 system activation was investigated. It was revealed that D1 partial agonism improved attentional performance in a baseline-dependent manner. Following successful acquisition of the task, it was shown that repeated PCP treatment induced cognitive disruption that was cognitive-specific, and not confounded by generalised response disruption. Furthermore, a partial attenuation of the PCP-induced performance disruption was achieved following administration of the D1 partial agonist, SKF 38393. Moreover, sub-chronic PCP treatment was shown to impair 5C-CPT performance in the drug-free state. However, an additional challenge that further increased the attentional load was needed to elucidate a performance deficit. This highlighted that sustained attention/vigilance is sensitive to persistent impairment following sub-chronic PCP administration in a manner consistent with deficits observed in schizophrenia patients. This prompted the investigation that tested the hypothesis that sub-chronic PCP treatment could induce enduring structural deficits in regions associated with attentional performance. Magnetic resonance imaging (MRI) was conducted, in conjunction with 5-CSRTT and pre-pulse inhibition (PPI). It was revealed that sub-chronic PCP treatment resulted in morphological brain abnormalities in brain regions associated with 5-CSRTT performance. This was coupled with deficits in sustained attentional performance following an increase in attentional load, yet PPI was unaffected. Taken together, these findings suggested sub-chronic PCP treatment impairs attentional functionality, an effect that dissociates between effortful and passive attentional processes.

Cette these reporte le développement d'un système d'architecture simple, resonant à 895 nm, utilisé pour la detection de resonances à piégeage coherent de population (CPT) de fort contraste dans des cellules à vapeur de cesium. Le système laser combine une diode laser DFB, un modulateur électro-optique d'intensité type Mach-Zehnder piloté à 4.596 GHz pour la génération de bandes latérales optiques séparées de 9.192 GHz et un système de type Michelson pour produire à terme un champ optique bichroamatique dont la polarisation est alternativement circulaire gauche et circulaire droite au rythme de la fréquence de Bohr des atomes. Ce schéma de polarisation CPT optimisé, proposé par le groupe de Happer à Princeton en 2004, permet de pomper optiquement un grand nombre d'atomes sur la transition d'horloge entre les sous-niveaux Zeeman 0-0 de l'état fondamental. Des techniques avancées ont été implémentées pour stabiliser la puissance laser, la suppression de porteuse optique en sortie de l'EOM et la fréquence laser. En utilisant ce montage, nous avons démontré la détection de résonances CPT avec un contraste de 80% dans des cellules Cs de dimensions centimétriques. Le contraste augmente avec la puissance laser au dépit d'un élargissement de la résonance CPT. Pour contourner ce problème, nous avons proposé la spectroscopie Ramsey de résonances CPT pour combiner fort contraste et faible largeur de raie. Dans ce montage, l'EOM est utilisé et pour la génération de bandes latérales optiques et comme un obturateur de lumière pour produire l'interaction Ramsey. Des franges de Ramsey de largeur 166 Hz et de contraste supérieur à 30% ont été détectées avec ce système. Ce système laser sera utilisé dans un future proche au sein d'une horloge atomique CPT de haute-performance.