Le proton est décrit par les facteurs de forme électrique et magnétique qui caractérisent sa structure interne. Le moyen de mesurer les facteurs de forme consiste à mesurer la distribution angulaire de la diffusion élastique e-p: dans cette région dite espace q^2 est négatif. En utilisant la réaction croisée pbar p<--> e+ e-, on atteint une autre région cinématique appelée région temps où q^2>0. Cependant, à cause du seuil q^2_{th} de les réactions pbar p <--> e+e-, seul le domaine cinématique q^2>q^2_{th}>0 est autorisé. Pour atteindre la région non physique, on utilise la réaction pbar p --> pi0e+e- où le pi0 emporte une partie de l'énergie autorisant ainsi q^2 à varier entre q^2_{th} et presque 0. Cette thèse vise à démontrer la faisabilité de ces mesures avec le détecteur PANDA qui sera installé sur l'anneau d'antiprotons du futur complexe FAIR à Darmstadt. Pour décrire la réaction pbar p --> pi0e+e- une approche basée sur des lagrangiens est développée. La section efficace 5 fois différentielle est determinée et reliée à des combinaisons linéaires de tenseurs hadroniques. Sous l'hypothèse de l'échange d'un nucléon, les tenseurs hadroniques sont exprimés en fonctions des 2 facteurs de forme électromagnétiques complexes du proton. Une méthode est développée, qui donne accès au rapport des facteurs de forme électromagnétiques du proton R=|G_E|/|G_M| et pour la première fois avec une expérience non polarisée au cosinus de la différence de phase. A ce jour, de telles mesures n'ont jamais été faites dans la région non physique. Des simulations détaillées ont été effectuées pour montrer comment le rapport R et le cosinus peuvent être extraits de la distribution angulaire du positron. De plus, un modèle est développé pour la réaction parasite pbar p-->pi0pi+pi- considérée comme la plus dangereuse. La contribution du bruit de fond peut être réduite à quelques pour-cent voire moins. L'efficacité typique de détection du signal correspondante varie de l'ordre de 5 pour-cent à 30 pour-cent. La précision sur la détermination du rapport R et du cosinus est determinée pour le nombre de coups attendu via la méthode Monte Carlo. Une partie de cette thèse est aussi dédiée à un travail plus technique avec l'étude du prototype du calorimètre électromagnétique et la détermination de sa résolution. / The proton is described by the electric G_E and magnetic G_M form factors which characterise its internal structure. The way to measure the proton form factors consists in measuring the angular distribution of the e-p elastic scattering accessing the so-called Space-Like region where q^2<0. Using the crossed channel pbar p<-->e+e-, one accesses another kinematical region, the so-called Time-Like region where q^2>0. However, due to the pbar p<-->e+e- threshold q^2_{th}, only the kinematical domain q^2>q^2_{th}>0 is available. To access the unphysical region, one may use the pbar p --> pi0e+e- reaction where the pi0 takes away a part of the system energy allowing q^2 to be varied between q^2_{th} and almost 0. This thesis aims to show the feasibility of such measurements with the PANDA detector which will be installed on the antiproton ring at the FAIR facility at Darmstadt. To describe the pbar p --> pi0e+e- reaction, a Lagrangian based approach is developed. The 5-fold differential cross section is determined and related to linear combinations of hadronic tensors. Under the assumption of one nucleon exchange, the hadronic tensors are expressed in terms of the 2 complex proton electromagnetic form factors. An extraction method which provides an access to the proton electromagnetic form factor ratio R=|G_E|/|G_M| and for the first time in an unpolarized experiment to the cosine of the phase difference is developed. Such measurements have never been performed in the unphysical region. Extended simulations were performed to show how the ratio R and the cosine can be extracted from the positron angular distribution. Furthermore, a model is developed for the pbar p-->pi0pi+pi- background reaction considered as the most dangerous one. The background contribution can be reduced to the percent level or even less. The corresponding signal efficiency ranges from a few % to 30%. The precision on the determination of the ratio R and of the cosine is determined using the expected counting rates via Monte Carlo method. A part of this thesis is also dedicated to more technical work with the study of the prototype of the electromagnetic calorimeter and the determination of its resolution.

The proton is described by the electric G_E and magnetic G_M form factors which characterise its internal structure. The way to measure the proton form factors consists in measuring the angular distribution of the e-p elastic scattering accessing the so-called Space-Like region where q^2<0. Using the crossed channel pbar p<-->e+e-, one accesses another kinematical region, the so-called Time-Like region where q^2>0. However, due to the pbar p<-->e+e- threshold q^2_{th}, only the kinematical domain q^2>q^2_{th}>0 is available. To access the unphysical region, one may use the pbar p --> pi0e+e- reaction where the pi0 takes away a part of the system energy allowing q^2 to be varied between q^2_{th} and almost 0. This thesis aims to show the feasibility of such measurements with the PANDA detector which will be installed on the antiproton ring at the FAIR facility at Darmstadt. To describe the pbar p --> pi0e+e- reaction, a Lagrangian based approach is developed. The 5-fold differential cross section is determined and related to linear combinations of hadronic tensors. Under the assumption of one nucleon exchange, the hadronic tensors are expressed in terms of the 2 complex proton electromagnetic form factors. An extraction method which provides an access to the proton electromagnetic form factor ratio R=|G_E|/|G_M| and for the first time in an unpolarized experiment to the cosine of the phase difference is developed. Such measurements have never been performed in the unphysical region. Extended simulations were performed to show how the ratio R and the cosine can be extracted from the positron angular distribution. Furthermore, a model is developed for the pbar p-->pi0pi+pi- background reaction considered as the most dangerous one. The background contribution can be reduced to the percent level or even less. The corresponding signal efficiency ranges from a few % to 30%. The precision on the determination of the ratio R and of the cosine is determined using the expected counting rates via Monte Carlo method. A part of this thesis is also dedicated to more technical work with the study of the prototype of the electromagnetic calorimeter and the determination of its resolution.

Colorectal cancer is the third leading cause of cancer-related mortality. Much progress has been achieved in combating this disease with surgical resection and chemotherapy in combination with targeted drugs. However, most metastatic patients develop drug resistance so new modalities of treatment are needed. Notch signaling plays a vital role in intestinal homeostasis, self-renewal, and cell fate decisions during post-development and is activated in colorectal adenocarcinomas. Under debate is its role in carcinomas and metastatic disease. In theory, blocking Notch activation using gamma-secretase inhibitors (GSIs) may show efficacy alone or in combination with chemotherapy in the treatment of colon cancer. In Chapter Three, we tested the capacity for GSIs to synergize with oxaliplatin in colon cancer cell lines and evaluated the underlying molecular mechanisms. GSI alone had no effect on colon cancer cell lines. Surprisingly, we show that GSIs blocked oxaliplatin-induced apoptosis through increased protein levels of the anti-apoptotic Bcl-2 proteins Mcl-1 and/or Bcl-xL. Restoration of apoptosis was achieved by blocking Mcl-1 and/or Bcl-xL with obatoclax (an anti-apoptotic Bcl-2 agonist) or siRNA. An unexpected result was the induction of cell death with the combination of GSI and obatoclax. In Chapter Four, we examined the mechanism of GSI + obatoclax-mediated cell death. We found that apoptosis played a minimal role. Rather, we identified blockage of cytoprotective autophagy played a causative role. Interestingly, we also saw autophagy induction in GSI-treated cells, which could explain the insensitivity of colon cancer cells to GSI. When autophagy was blocked in GSI-treated cells, cells became sensitive to GSI and cell death was elicited. The mechanism by which induction of autophagy occurs in GSI- treated cells is an area for further research. Overall, our work questions the validity of the use of GSIs in the treatment of colorectal cancers. We show that GSIs may block apoptosis and induce cytoprotective autophagy simultaneously, resulting in increased drug resistance and cellular survival. Whether these two cellular survival processes occurs in patients needs to be examined before GSIs can be utilized in a clinical setting. If so, these two hurdles must be overcome.

This research presents the methodologies used to resolve the Nuclear Regulatory Commission Generic Safety Issue 191. The presented results are specific to South Texas Project Nuclear Operating Company (STPNOC). However, the proposed methodologies may be applicable to other nuclear power plants given the appropriate plant-specific frequencies. This research provides important inputs to CASA Grande, a computer program used to model physical phenomena and quantify uncertainties to obtain estimates of failure probabilities for post-loss-of-coolant accident events at the STPNOC containment. We provide modeling and sampling methods for loss-of-coolant accident (LOCA) frequencies and break sizes. We focus on a study known as NUREG-1829 (Tregoning et al., 2008), which includes an expert elicitation of quantiles governing the (annual) frequency of a LOCA in boiling water reactors and pressurized water reactors. We propose to model LOCA frequencies with bounded Johnson distributions and to sample break sizes using uniform distributions. We then develop a new method to distribute LOCA frequencies to different locations within a plant to account for the location-dependent differences while preserving the NUREG-1829 frequencies. We also propose to linearly interpolate the NUREG-1829 LOCA frequencies to obtain the frequencies for any break sizes other than those from NUREG-1829. In addition, we present a method to obtain the distribution of LOCA frequency within a break-size interval providing important inputs to the probabilistic risk assessment quantification for STPNOC. We review methods of combining the probability distributions of multiple experts to obtain a single probability distribution. More specifically, we describe the relative merits of the arithmetic mean (AM) and geometric mean (GM) as ways of performing this aggregation in the context of probabilities associated with rare events. Examining a set of pressurized water reactor results from NUREG-1829, we conclude that the GM represents a consistently sensible notion of the middle of the opinions expressed by nine experts. We further conclude that the AM is inappropriate for representing the center of the group's opinion for large effective break sizes. Instead, as the break size grows large a single expert's opinion dominates the combination produced by the AM. / text

Particle-surface interactions govern a myriad of interface phenomena, that span from technological applications to naturally occurring biological processes. In the present work, particle-collector DLVO interactions are computed with the grid-surface integration (GSI) technique, previously applied to the computation of particle colloidal interactions with anionic surfaces patterned with O(10 nm) cationic patches. The applicability of the GSI technique is extended to account for interactions with collectors covered with topographical and chemical nanoscale heterogeneity. Surface roughness is shown to have a significant role in the decrease of the energy barriers, in accordance with experimental deposition rates that are higher than those predicted by the DLVO theory for smooth surfaces. An energy- and force-averaging technique is presented as a reformulation of the GSI technique, to compute the mean particle interactions with random heterogeneous collectors. A statistical model based on the averaging technique is also developed, to predict the variance of the interactions and the particle adhesion thresholds. An excellent agreement is shown between the models' predictions and results obtained from GSI calculations for large number of random heterogeneous collectors. Brownian motion effects for particle-collector systems governed by nanoscale heterogeneity are analyzed by introducing stochastic Brownian displacements in particle trajectory equations. It is shown that for the systems under consideration and particle sizes usually used in experiments, it is reasonable to neglect the effects of Brownian motion entirely. Computation of appropriately defined P ́eclet numbers that quantify the relative importance of shear, colloidal and Brownian forces validate that conclusion. An algorithm for the discretization of spherical surfaces into small equal-area elements is implemented in conjunction with the GSI technique and mobility matrix calculations of particle velocities, to obtain interactions and dynamic behaviors of patchy particles in the vicinity of uniform flat collectors. The patchy particle and patchy collector systems are compared in detail, through the computation of statistical measures that include adhesion probabilities and maximum residence times per patch. The lessened tendency of the patchy particle to adhere on the uniform collector is attributed to a larger maximum residence time per patch, which precludes interactions with multiple surface nano-features at a given simulated time. Also briefly described are directions for future work, that involve the modeling of two heterogeneous surfaces, and of surfaces covered with many types of heterogeneity, such as patches, pillars and spring-like structures that resemble polymer brushes or cellular receptors.

No description available.

<p>This thesis reports the results of biomarker measurements in three environmental monitoring projects. In the first project, which was part of the Swedish national environmental monitoring, biomarkers were measured annually in female perch (<i>Perca fluviatilis</i>) in two background areas in the Baltic Sea during 1988–2000, resulting in a unique 13-year series of measurements. The most important results were a strong decreasing temporal trend in the gonadosomatic index (GSI) and a strong increasing temporal trend in the hepatic ethoxyresorufin O-deethylase (EROD) activity in the Baltic Proper. In the second project, biomarkers and concentrations of classic pollutants were measured in female perch in the Stockholm recipient 1999–2001. This was the first time a large city was investigated as a point source of pollution, and the gradient was longer and included more stations than customary. Severe pollution conditions in central Stockholm were indicated by the poor health status of the perch: retarded growth, decreased frequency of sexually mature females, low GSI, disturbed visceral fat metabolism, increased hepatic EROD activity, decreased muscle acetylcholinesterase activity, increased frequency of hepatic DNA adducts, and a high concentration of biliary 1-pyrenol. Muscle ΣDDT and ΣPCB were measured as pollution indicators and were 10–28 respectively 12–35 times higher than the background levels in perch from the Baltic Proper. In the Stockholm archipelago two superimposed gradients were found. Whereas the response of several biomarkers consistently decreased with increasing distance from central Stockholm, the response of others first decreased from Stockholm to the middle archipelago and then increased to the open Baltic Sea. The latter biomarkers included the frequency of sexually mature females, GSI, hepatic EROD activity, and hepatic DNA adducts. In the third project, potential toxicity from munitions on the seafloor, at a dumpsite in the Stockholm archipelago, was analysed by the nanoinjection of sediment extracts into newly fertilised rainbow trout (<i>Oncorhynchus mykiss</i>) eggs, followed by the measurement of biomarkers in the developing larvae. No biological effects of the dumped munitions were found. The same stations in the Stockholm archipelago as in the second project were investigated as a positive control. The results of the three projects agreed well, which demonstrated the continuous pollution of the Baltic Sea and the severe pollution conditions and adverse biological effects in central Stockholm. Further investigations are urgently needed to identify which pollutants or other factors are causing the observed biological effects, both in the background areas in the Baltic Sea and in the Stockholm recipient.</p>

This thesis reports the results of biomarker measurements in three environmental monitoring projects. In the first project, which was part of the Swedish national environmental monitoring, biomarkers were measured annually in female perch (Perca fluviatilis) in two background areas in the Baltic Sea during 1988–2000, resulting in a unique 13-year series of measurements. The most important results were a strong decreasing temporal trend in the gonadosomatic index (GSI) and a strong increasing temporal trend in the hepatic ethoxyresorufin O-deethylase (EROD) activity in the Baltic Proper. In the second project, biomarkers and concentrations of classic pollutants were measured in female perch in the Stockholm recipient 1999–2001. This was the first time a large city was investigated as a point source of pollution, and the gradient was longer and included more stations than customary. Severe pollution conditions in central Stockholm were indicated by the poor health status of the perch: retarded growth, decreased frequency of sexually mature females, low GSI, disturbed visceral fat metabolism, increased hepatic EROD activity, decreased muscle acetylcholinesterase activity, increased frequency of hepatic DNA adducts, and a high concentration of biliary 1-pyrenol. Muscle ΣDDT and ΣPCB were measured as pollution indicators and were 10–28 respectively 12–35 times higher than the background levels in perch from the Baltic Proper. In the Stockholm archipelago two superimposed gradients were found. Whereas the response of several biomarkers consistently decreased with increasing distance from central Stockholm, the response of others first decreased from Stockholm to the middle archipelago and then increased to the open Baltic Sea. The latter biomarkers included the frequency of sexually mature females, GSI, hepatic EROD activity, and hepatic DNA adducts. In the third project, potential toxicity from munitions on the seafloor, at a dumpsite in the Stockholm archipelago, was analysed by the nanoinjection of sediment extracts into newly fertilised rainbow trout (Oncorhynchus mykiss) eggs, followed by the measurement of biomarkers in the developing larvae. No biological effects of the dumped munitions were found. The same stations in the Stockholm archipelago as in the second project were investigated as a positive control. The results of the three projects agreed well, which demonstrated the continuous pollution of the Baltic Sea and the severe pollution conditions and adverse biological effects in central Stockholm. Further investigations are urgently needed to identify which pollutants or other factors are causing the observed biological effects, both in the background areas in the Baltic Sea and in the Stockholm recipient.

The main purpose of this thesis is to explore experiences of two different psychological interventions based on art psychotherapy in women with a psychological or physical illness. The two interventions are art psychotherapy and art therapy. The difference between these two interventions is that the art therapist works with the transference in art psychotherapy but not in art therapy. The thesis consists of two studies of art psychotherapy: An art psychotherapy intervention is evaluated in Study 1 (papers III and V) which examines a group of patients diagnosed with depression and Study 2 (paper II) which examines experiences in a group of six patients diagnosed with vulva vestibulitis. An art therapy intervention is evaluated in the third study (papers I and IV); where experiences in patients diagnosed with breast cancer are examined. In Study 1, forty-three (n=43) depressed women were randomly assigned to either an intervention group or a control group (verbal psychotherapy). The aim was to examine the outcome of time limited psychodynamic art therapy compared to time-limited psychodynamic verbal therapy for patients with depressive symptoms. Interviews were performed before, immediately after, and three months after the termination of psychotherapy, and self-rating scales which focus on stress reactions, depression and symptoms as well as an observer rating scale on depression were used. The interviews and the art sessions were video-recorded, and the verbal psychotherapy was tape-recorded. The results showed that the art and verbal psychotherapies were comparable. The conclusion was that short-term psychodynamic art psychotherapy could be a valuable treatment for depressed women. In an in-depth content analysis, the method of scribbling was further investigated and exemplified with the therapies of two participants. In this study, the patients’ pictures and verbal expressions of progress, along with considerations of how to interpret the pictures were in focus. When leaving therapy the two patients took advantage of the paper, made complete forms, symbolised in words what they have expressed in pictures; in pace with psychotherapy the themes alter towards separation, individuation, and attempt to relate in a new way. The conclusion was that limelimited psychodynamic art therapy suggests giving a safer place for the self as the cohesion is firmer with better boundaries. Study 2 is a pilot study, which involved six young patients newly diagnosed with vulva vestibulitis. The aim of the study was to investigate pain at vestibulum, mental health, and self-image after fifteen sessions of art psychotherapy. Five of the patients were judged to have less pain three months after termination of therapy. The conclusion was that art psychotherapy with its openness seemed to affect young women in their experiences of vulva vestibulitis in a positive direction. Study 3 examined the potential benefit of art therapy for women with primary breast cancer. The sample comprised forty-one (n=41) patients who were randomly assigned either to an art therapy group or to a control group. The art therapy was going on during five weeks radiation treatment, one session per week. The aim was to investigate the outcome of art therapy, to quantify and compare the participant coping s, self-image, and the symptoms with the participant in the control group. Interviews were performed before, immediately after, and six month after inclusion. A set of self-rating scales was used: Coping Resources Inventory, the Structural Analysis of Social Behavior, and Symptom Check List – 90. The result showed that the patients in the art therapy group rated their coping s and especially their social s, higher than the control group, and that the average patients in the art therapy group improved in depressive symptoms and symptoms of anxiety, and that the general psychiatric symptoms improved as well. A linear regression analysis showed a tendency that the coping s increased in the art therapy group and decreased in the control group or even stagnated in the social domain. A second report on self-image, symptoms, treatment, and social variables showed that art therapy was related to lower ratings of depression, anxiety, and general symptoms after treatment; chemotherapeutic treatment predicted lower depressive symptoms and general symptoms in contrast to axilliary surgery and hormonal treatment. The results showed that art therapy could be valuable complementary therapy in routine oncology practise. The conclusion is that art therapy can have a positive long-term effect on the crisis following the primary breast cancer and its consequences. Conclusion: The results show that time-limited psychodynamic art psychotherapy is valuable for depressed women; that it is a valuable complement for women with vulva vestibulitis; and that art therapy is a valuable complement in the care and cure of women with primary breast cancer.

In this thesis, the results of a number of rock mass classification systems applied to Dim-higway tunnel study area are presented. The tunnel ground was classified according to Rock Mas Rating (RMR), Modified Rock mass Rating (M-RMR), Rock mass quality (Q), Geological Strength Index (GSI) and New Austrian Tunneling Method (NATM). Dim Tunnel has a horse-shoe shape, with a diameter of 10 meters and maximum overburden thickness of 70 meters. During studies, the geological and geotechnical characteristics of the rock mass along the Dim Tunnel route were investigated. The main objective of rock mass classifications carried out in this study was to obtain adequate data that could be used in future excavation and support-design studies. In order to accomplish this task, literature survey was carried out, followed by a comprehensive field study and laboratorytesting. Field studies involved detailed discontinuity surveys of the exposed rock mass at the surface and on the cores taken within 10-20 meters of the borehole above the tunnel. A geological map and a geological cross-section along the tunnel axis were also prepared. Finally, correlations between the results of the rock mass classification systems were made carrying out statistical analyses for the Dim Tunnel study area. The results obtained from the RMR and M-RMR classifications indicate that M-RMR system estimates better rock mass quality ratings at the upper bounds of the rock mass condition, but worst ratings at the lower bounds (RMR is less than 40) as also suggested by the previous studies.