<p>As evidenced by several trials, cognitive behavior therapy (CBT) is a highly effective treatment for Panic disorder with or without agoraphobia (PD). However, therapists are short in supply, and patients with agoraphobia may not seek therapy due to fear of leaving their homes or traveling certain distances. A major challenge therefore is to increase the accessibility and affordability of evidence-based psychological treatments.</p><p>This thesis is based on five studies; three treatment studies set up as randomized controlled trails (RCT), one prevalence study, and one study testing the equivalence of an Internet-administered diagnostic assessment tool with a clinician-administered interview.</p><p>Study I showed that the Swedish 12-month PD prevalence is consistent with findings in most other parts of the Western world (2.2%; CI 95% 1.0%-3.4%). There was a significant sex difference, with a greater prevalence for women (3.6%) compared to men (0.7%).</p><p>Study II showed that the validity of the computerized diagnostic interview (CIDI-SF) was generally low. However, the agoraphobia and obsessive-compulsive disorder modules had good specificity and sensitivity, respectively.</p><p>The three RCTs showed, directly or indirectly, that Internet-based self-help is superior to a waiting-list. When 10 individual weekly sessions of CBT for PD was compared with a 10-module self-help program on the Internet, the results suggest that Internet-administered self-help, plus minimal therapist contact via e-mail, is as effective as traditional individual CBT (80% vs. 67% no longer met criteria for panic disorder; composite within-group effect size was Cohen’s <i>d</i>= 0.78 vs. 0.99). One-year follow-up confirmed the results (92% vs. 88% no longer met criteria for panic disorder; <i>d</i>= 0.80 vs. 0.93). The results generally provide evidence to support the continued use and development of Internet-distributed self-help programs.</p>

As evidenced by several trials, cognitive behavior therapy (CBT) is a highly effective treatment for Panic disorder with or without agoraphobia (PD). However, therapists are short in supply, and patients with agoraphobia may not seek therapy due to fear of leaving their homes or traveling certain distances. A major challenge therefore is to increase the accessibility and affordability of evidence-based psychological treatments. This thesis is based on five studies; three treatment studies set up as randomized controlled trails (RCT), one prevalence study, and one study testing the equivalence of an Internet-administered diagnostic assessment tool with a clinician-administered interview. Study I showed that the Swedish 12-month PD prevalence is consistent with findings in most other parts of the Western world (2.2%; CI 95% 1.0%-3.4%). There was a significant sex difference, with a greater prevalence for women (3.6%) compared to men (0.7%). Study II showed that the validity of the computerized diagnostic interview (CIDI-SF) was generally low. However, the agoraphobia and obsessive-compulsive disorder modules had good specificity and sensitivity, respectively. The three RCTs showed, directly or indirectly, that Internet-based self-help is superior to a waiting-list. When 10 individual weekly sessions of CBT for PD was compared with a 10-module self-help program on the Internet, the results suggest that Internet-administered self-help, plus minimal therapist contact via e-mail, is as effective as traditional individual CBT (80% vs. 67% no longer met criteria for panic disorder; composite within-group effect size was Cohen’s d= 0.78 vs. 0.99). One-year follow-up confirmed the results (92% vs. 88% no longer met criteria for panic disorder; d= 0.80 vs. 0.93). The results generally provide evidence to support the continued use and development of Internet-distributed self-help programs.

This thesis is a guide to building a sustainable rail-trail, wherein I focus on invasive species removal, green pavement, and creating an inviting space with the inclusion of integrated art. When the City of Kirkland, WA purchased the 5.75 mile long section of railroad going through the city, I approached city manager Kurt Triplett to ask about his plans for the corridor. He liked the idea of aiming for a sustainable trail, so I wrote a guide to building an environmentally friendly trail based on a number of prominent readings on sustainable design.

The New Albany Shale is an Upper Devonian organic-rich gas shale located in the Illinois Basin. A factor influencing gas production from the shale is the natural fracture system. I test the hypothesis that a combination of outcrop and core observations, rock property tests, and geomechanical modeling can yield an accurate representation of essential natural fracture attributes that cannot be obtained from any of the methods alone. Field study shows that New Albany Shale outcrops contain barren (free of cement) joints, commonly oriented in orthogonal sets. The dominant set strikes NE-SW, with a secondary set oriented NNW-SSE. I conclude that the joints were likely created by near-surface processes, and thus are unreliable for use as analogs for fractures in the reservoir. However, the height, spacing, and abundance of the joints may still be useful as guides to the fracture stratigraphy of the New Albany Shale at depth. The Clegg Creek and Blocher members contain the highest fracture abundance. Fractures observed in four New Albany Shale cores are narrow, steeply-dipping, commonly completely sealed with calcite and are oriented ENE-WSW. The Clegg Creek and Blocher members contain the highest fracture abundance, which is consistent with outcrop observations. Fractures commonly split apart along the wall rock-cement interface, indicating they may be weak planes in the rock mass, making them susceptible to reactivation during hydraulic fracturing. Geomechanical testing of six core samples was performed to provide values of Young’s modulus, subcritical index, and fracture toughness as input parameters for a fracture growth simulator. Of these inputs, subcritical index is shown to be the most influential on the spatial organization of fractures. The models predict the Camp Run and Blocher members to have the most clustered fractures, the Selmier to have more evenly-spaced fractures, and the Morgan Trail and Clegg Creek to have a mixture of even spacing and clustering. The multi-faceted approach of field study, core work, and geomechanical modeling I used to address the problem of fracture characterization in the New Albany Shale was effective. Field study in the New Albany presents an opportunity to gather a large amount of data on the characteristics and spatial organization of fractures quickly and at relatively low cost, but with questionable reliability. Core study allows accurate observation of fracture attributes, but has limited coverage. Geomechanical modeling is a good tool for analysis of fracture patterns over a larger area than core, but results are difficult to corroborate and require input from outcrop and core studies. / text

The mammalian pregnancy comprises a challenge to the maternal immune system since the fetus is semi-allogeneic and could thus be rejected. Pregnancy success is associated with the placenta that is not only essential for oxygen supply, nourishment and pregnancy hormones but also plays a role in the protection of the fetus against maternal immunologic attack. The aim of the current studies was to elucidate the role of human placenta as an immunomodulatory organ with a special focus on placental exosomes as vehicles for establishment of maternal tolerance to the fetus. We discovered that the syncytiotrophoblast in human normal pregnancy constitutively produces and secretes exosomes. Exosomes are 30-100 nanometer-sized membrane vesicles of endosomal origin that convey intercellular communication. Exosomes are produced and released through the endosomal compartment and reflect the type and the activation state of the cells that produce and secrete them. They carry cytosolic and membrane-bound proteins and nucleic acids and can influence and re-program recipient cells. Depending on their interactions with cells of the immune system they can be divided into immunostimulatory or immunosuppressive. We developed methods for isolation and culture of trophoblast and placental explants from human normal first trimester pregnancy and isolated exosomes from the culture supernatants.  These exosomes were characterized biochemically and functionally regarding mechanisms with potential importance in the establishment of maternal tolerance towards the fetus. The following aspects were studied: 1) exosomal modulation of the NKG2D receptor-ligand system, a major cytotoxic pathway for NK- and cytotoxic T cells and thus potentially dangerous to the fetus; 2) placental exosome-mediated apoptosis of activated immune effector cells; and 3) Foxp3-expressing T regulatory cells in human pregnant uterine mucosa, the decidua. Using immuno electron microscopy we show that human early syncytiotrophoblast constitutively expresses the stress-inducible NKG2D ligands MICA/B and ULBP1-5, and the apoptosis inducing molecules FasL and TRAIL. While MICA/B were expressed both on the cell surface and intracellularly on the limiting membrane of multivesicular bodies (MVB) and on exosomes, the ULBP1-5, FasL and TRAIL  were solely  processed through the MVB of the endosomal compartment and secreted on exosomes. The NKG2D ligand-expressing placental exosomes were able to internalize the cognate receptor from the cell surface of activated NK- and T cells thus down regulating their cytotoxic function. In our studies of apoptosis we found that placental exosomes carry the proapoptotic ligands FasL and TRAIL in their active form as a hexameric complex of two homotrimeric molecules, required for triggering of the apoptotic signaling pathways. This finding was supported by the ability of isolated placental FasL/TRAIL expressing exosomes to induce apoptosis in activated peripheral blood mononuclear cells (PBMC) and Jurkat T cells. Additionally, we studied Foxp3-expressing T regulatory (Treg) cells in paired human decidual and blood samples from pregnant women compared to non-pregnant controls. The CD4+CD25+Foxp3+ Treg cells were 10 fold enriched in the decidual mucosa compared to peripheral blood of pregnant women and non-pregnant controls. We discovered a pool of Foxp3-expressing, CD4+CD25- cells in human decidua, a phenotype consistent with naïve/precursor Foxp3+ Treg cells. These results suggest local enrichment of Treg cells in decidua of normal pregnancy. Furthermore, we have results indicating that the exosomes, isolated from placental explant cultures, carry PD-L1 and TGFβ on their surface, molecules known to promote induction of Treg cells. Taken together, our results provide evidence that placental exosomes are immunosuppressive and underline their role in the maternal immune modulation during pregnancy. The constitutive production and secretion of immunosuppressive placental exosomes create a protective exosomal gradient in the blood surrounding the feto-placental unit. This “cloud of immunosuppressive exosomes” conveys immunologic privilege to the developing fetus and thus contributes to the solution of the immunological challenge of mammalian pregnancy.

TRAIL (TNF-related apoptosis inducing ligand) est une protéine du système immunitaire appartenant à la famille du TNF (Tumor necrosis factor). L'intérêt de TRAIL en thérapie anti-cancéreuse réside dans sa capacité à induire la mort par apoptose des cellules tumorales, sans exercer de toxicité envers les cellules saines. Le principal frein à l'utilisation de TRAIL est la survenue de mécanismes de résistance à TRAIL dans certaines tumeurs. Mon travail de thèse a consisté à étudier ces mécanismes de résistance à TRAIL et à élaborer des stratégies visant à les contourner. Dans un premier temps, mon intérêt s'est porté sur le récepteur antagoniste TRAIL-R4, qui est capable de fixer TRAIL sans engager de signal de mort. Nous avons montré pour la première fois que TRAIL-R4 est à l'origine de l'induction de voies de signalisation intracellulaires de survie et de prolifération dans le modèle HeLa de carcinome du col de l'utérus. Ces cellules résistantes peuvent néanmoins être sensibilisées à l'action de TRAIL par un pré-traitement chimiothérapeutique conventionnel (cisplatine, étoposide ou 5-FU). Cette sensibilisation ne fait pas intervenir la voie mitochondriale de l'apoptose, mais passe par une augmentation du recrutement et de l'activation de la caspase-8 au sein du complexe initiateur de mort (DISC). Dans un deuxième temps, mon travail s'est focalisé sur des lymphomes B non-Hodgkiniens particulièrement agressifs, les lignées VAL et RL. La résistance à TRAIL de ces lymphomes est due à un blocage de la voie mitochondriale de l'apoptose, notamment en raison de l'expression des protéines anti-apoptotiques Bcl-2, Mcl-1 et survivine. Mon objectif a été d'élaborer une stratégie thérapeutique visant à contourner cette résistance. Dans ce contexte, nous avons évalué l'efficacité d'un composé polyphénolique issu des plantes, la quercétine. Nos résultats montrent que la combinaison de la quercétine et de TRAIL permet de tuer de façon synergique les lymphomes VAL et RL. Le mécanisme moléculaire de cette synergie comprend l'activation de la voie mitochondriale de l'apoptose, ainsi que l'inhibition de Mcl-1 et de la survivine. L'ensemble de ce travail est rassurant quant à l'utilisation de la cytokine TRAIL en thérapie anti-tumorale, dans le cadre d'une thérapie combinée.

Fault management is a challenging task in all-optical wavelength division multiplexing (WDM) networks. However, fast fault localization for shared risk link groups (SRLGs) with multiple links is essential for building a fully survival and functional transparent all-optical mesh network. Monitoring trail (m-trail) technology is an effective approach to achieve the goal, whereby a set of m-trails are derived for unambiguous fault localization (UFL). However, an m-trail traverses through a link by utilizing a dedicated wavelength channel (WL), causing a significant amount of resource consumption. In addition, existing m-trail methods incur long and variable alarm dissemination delay. We introduce a novel framework of real-time fault localization in all-optical WDM mesh networks, called the monitoring-burst (m-burst), which aims at initiating a balanced trade-off between consumed monitoring resources and fault localization latency. The m-burst framework has a single monitoring node (MN) and requires one WL in each unidirectional link if the link is traversed by any m-trail. The MN launches short duration optical bursts periodically along each m-trail to probe the links of the m-trail. Bursts along different m-trails are kept non-overlapping through each unidirectional link by scheduling burst launching times from the MN and multiplexing multiple bursts, if any, traversing the link. Thus, the MN can unambiguously localize the failed links by identifying the lost bursts without incurring any alarm dissemination delay. We have proposed several novel m-trail allocation, burst launching time scheduling, and node switch fabric configuration schemes. Numerical results show that the schemes, when deployed in the m-burst framework, are able to localize single-link and multi-link SRLG faults unambiguously, with reasonable fault localization latency, by using at most one WL in each unidirectional link. To reduce the fault localization latency further, we also introduce a novel methodology called nested m-trails. At first, mesh networks are decomposed into cycles and trails. Each cycle (trail) is realized as an independent virtual ring (linear) network using a separate pair of WLs (one WL in each direction) in each undirected link traversed by the cycle (trail). Then, sets of m-trails, i.e., nested m-trails, derived in each virtual network are deployed independently in the m-burst framework for ring (linear) networks. As a result, the fault localization latency is reduced significantly. Moreover, the application of nested m-trails in adaptive probing also reduces the number of sequential probes significantly. Therefore, practical deployment of adaptive probing is now possible. However, the WL consumption of the nested m-trail technique is not limited by one WL per unidirectional link. Thus, further investigation is needed to reduce the WL consumption of the technique.

Thesis (D.A.)--Illinois State University, 2000. / Title from title page screen, viewed May 4, 2006. Dissertation Committee: Frederick D. Drake (chair), Lawrence W. McBride, M. Paul Holsinger, L. Moody Simms. Includes bibliographical references (leaves 245-254) and abstract. Also available in print.

This diploma thesis deals with the monitoring of the movement of machines on the land and their influence on soil compaction. In the practical part, measurements and observation were carried out in the company Rolnická společnost Lesonice a.s Within two years, the values of individual sets were measured on the selected land and the values were compared between each other. Every year, other soil technology was implemented. 1st year minimalization technology for soil cultivation 2nd year StripTiil's Soil Technology, controlled motion across the land with designed Opti Trail plot lines.

xv, 298 p. ; ill. (chiefly col.), maps (chiefly col.) A print copy of this thesis is available through the UO Libraries under the call number: AAA F868.Y6 G47 2004 / This study describes existing conditions, evaluates significance and historic integrity, and recommends treatment strategies to preserve historic elements of the Nevada Fall Corridor cultural landscape in Yosemite National Park. It reports findings from field investigation that examined and inventoried landscape features such as stone retaining walls, treadway material, bridges and causeways, and water features on both current-use and abandoned trail segments. The site was examined numerous times over a three-month period, with a followup visit one year later. Libraries and other archives were consulted for written and photographic historic documentation, which were analyzed against current conditions. The process also involved review of comparison documents as well as national guidelines set forth by the National Park Service. / Adviser: Melnick, Robert Z.