This study examined the utility of the Trail Making Test Quotient (Trails B/ Trails A) in assessing executive functioning relative to that of common tests of executive function such as the Wisconsin Card Sorting Test, Category Test, and the Stroop Test. The purpose of the current study was to investigate the relationship of the Trail Making Test Quotient (Trails B/ Trails A) with other common tests of executive functioning (i.e., Wisconsin Card Sorting Test, Stroop, Category Test) to determine whether these tests are measuring similar domains of functioning or whether Trail Making Test Quotient (Trails B/ Trails A) offers a more pure measure of executive functioning over and beyond that of Trail Making Test B alone or the difference score, Trail Making Test (Trails B- Trails A). A series of partial correlations were conducted involving the Trail Making Test scores (Quotient, Difference, and B [Raw]), and the scores of the executive functioning measures (Wisconsin Card Sorting Test, Category Test, and Stroop), controlling for age, education, and gender. Trails Quotient, Trails B Raw, and Trails Difference were found to significantly negatively correlate with WCST Total # of Categories. Only Trails B Raw and Trails Difference were found to significantly positively correlate with WCST Perseverative Responses and Category Error. None of the Trail Making Test measures used in this study were found to significantly correlate Stroop Interference. Correlation coefficients were compared to determine the strength of Trails Quotient's relationship with the aforementioned executive functioning measures relative to that of Trails Difference and Trails B Raw. Contrary to the hypotheses of the current study, the Trails Quotient demonstrated a significantly weaker correlation with WCST Total # of Categories, WCST Perseverative Responses, and Category Error than that of Trails Difference and Trails B Raw. Additionally, there were no significant differences in the correlation coefficients of Trails Quotient, Trails Difference, and Trails B Raw with Stroop Interference. However, upon further investigation using exploratory factor analyses, it was discovered that Trails Quotient may have represented a particular component of executive functioning more so than the Trails Difference and Trails B Raw. The results suggest that Trails Quotient offers a unique estimate of executive skill specific to cognitive organization, whereas Trails B Raw and Trails Difference represent multiple executive domains including regulatory and organizational abilities. Clinical practice will benefit from the current study's findings in that assessment of complex executive functioning will be more precise. Future research is needed to determine the utility of the Trails Quotient in identifying specific types and locations of brain injury. Assessment of specific impaired frontal skills common to degenerative dementias and traumatic brain injury may be possible with the use of Trails Quotient contingent upon further research. Future research into the domains of executive functioning and the Trail Making Test should focus on specific skills within regulatory and organizational components, and the development of normative data for Trails Quotient.

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a potentially useful anticancer agent with exquisite selectivity for cancer cells. Unfortunately, many cancers exhibit or acquire resistance to TRAIL. We report herein that TRAIL activates a TGF-ß-activated kinase 1→mitogen-activated protein kinase (MAPK) kinase 3 (MKK3)/MKK6→p38 pathway in prostate cancer cells that transcriptionally upregulates expression of the antiapoptotic BCL-2 family member MCL-1. TRAIL alone triggered robust formation of the "death-inducing signaling complex", activation of the initiator caspase-8, and truncation of the BH3-only protein BID (tBID). Nevertheless, simultaneous disruption of the p38 MAPK pathway was required to suppress MCL-1 expression, thereby allowing tBID to activate the proapoptotic BCL-2 family member BAK and stimulate mitochondrial outer membrane permeabilization (MOMP). Release of the inhibitor-of-apoptosis antagonist, Smac/DIABLO, from the intermembrane space was sufficient to promote TRAIL-induced apoptosis, whereas release of cytochrome c and apoptosome function were dispensable. Even following MOMP, however, mitochondrial-generated reactive oxygen species activated a secondary signaling pathway, involving c-Jun N-terminal kinases, that likewise upregulated MCL-1 expression and partially rescued cells from death. Thus, stress kinases activated at distinct steps in the extrinsic pathway mediate TRAIL resistance through maintenance of MCL-1 expression. / text

Par‐4 is a pro‐apoptotic tumor suppressor that is mutated, suppressed or inactivated in cancer. Par‐4 exploits components of the extrinsic pathway to cause apoptosis selectively of cancer cells. This study identified Par‐4 as an essential component of the apoptotic pathway induced by TRAIL, which selectively targets cancer cells. RNA interference‐mediated knockdown of Par‐4 rendered cancer cells unresponsive to TRAIL‐induced apoptosis. Cells with knocked‐down levels of Par‐4 were deficient in the activation of the apoptosis‐initiator caspase‐8 and the apoptosis‐effector caspase‐3 in response to TRAIL. Par‐4 was identified as a critical mediator of membrane translocation of caspase‐8 and the adapter protein FADD. Surprisingly, Par‐4 was also found to interact with caspase 8 in untreated cells, and was cleaved at the N‐terminus at aspartic acid residue 123 in response to TRAIL. This, along with another cleavage by caspase‐9 effectively generated a fragment containing the functional module of Par‐4, the SAC domain, which is sufficient for apoptosis of cancer cells. Moreover, TRAIL activated caspase‐8 was also found to be involved in nuclear translocation of Par‐4, a crucial step during apoptosis induction by Par‐4. Together, our findings suggest that Par‐ 4 is an essential downstream target of caspase‐8 that is activated by TRAIL signaling and that, in turn, activates caspase‐8 and the downstream apoptotic pathway in response to TRAIL.

Anti-tumor therapeutic strategies based on combinations of chemotherapeutic agents with a death inducing ligand such as TNF-α Related Apoptosis Inducing Ligand (TRAIL), are directed towards selective and effective cancer cell apoptosis and enhanced therapeutic response. We previously demonstrated that proteasome inhibition sensitizes TRAIL resistant prostate cancer cells to TRAIL-mediated apoptosis via stabilization of the active p18 subunit of initiator caspase-8. The present study investigated the functional link between caspase-8 and the proteasome, by analyzing the impact of caspase-8 ubiquitination and proteasomal degradation on the outcomes of the extrinsic apoptosis pathway in cancer cells. Caspase-8 ubiquitination status was assessed by polyubiquitin immunoprecipitation (IP) and fluorescent microscopy. Apoptosis induction in response to death receptor stimuli or proteasome inhibitor was evaluated using the Annexin V/Propidium iodide staining (PI). To determine the consequences of proteasome inhibition on caspase-8 stability, trafficking, and activity following death receptor activation, we used the TRAIL-resistant human prostate cancer LNCaP cells, and the caspase-8 deficient Neuroblastoma 7 (NB7) cells, as cellular models for reconstituting the non-cleavable mutant forms of caspase-8. Our findings demonstrate that the non-cleavable forms of caspase-8 are capable of inducing apoptosis comparably to wild-type caspase-8 upon treatment with proteasome inhibitor and GST-TRAIL. Furthermore, caspase-8 processing into its active subunits preceded caspase-8 polyubiquitination, implicating caspase-8 processing as a potential regulatory mechanism, rather than a requirement for caspase-8 activation in apoptosis induction. The mechanistic control of caspase-8 by ubiquitination in cancer cells may have significant significance in bypassing mechanisms of therapeutic resistance in human tumors and optimization of anti-cancer treatment strategies in human tumors and optimization of anti-cancer treatment strategies.

The overall objective of the American Indian study is the preparation of a written report focusing on the ethnohistory and contemporary perspectives of selected communities affected by the Old Spanish Trail (OST). The project can be divided into two separate but related parts: (1) a brief history of each community under study and its historic relationship to OST, and (2) a description of contemporary community views of the trail. Of special interest will be any contemporary knowledge related to the role played by the trail (and/or events related to the trail’s history and use) that affected the history and perspective of each community. Also of interest will be any places or resources along the trail that have significant cultural meaning to the subject communities. These are often referred to as “ethnographic resources.” This report describes American Indian responses to various activities along the OST during its pack-train period, which was roughly from 1829 to 1849. The Indian responses are diachronic beginning with the first contacts by Indian people residing on and using traditional Indian trails which were to be used for pack-trains to and from California and culminating decades later when the full impacts of pack-train use had been absorbed and responded to by these proximal Indian peoples. While there were contacts between Indian people and Euro-Americans before 1829, commercial traffic along the OST initiated unprecedented and sustained American Indian natural resource and social impacts. This report describes the places involved and responses received from American Indian tribal representatives during the field visits conducted from June 2006 to June 2007. This report helps both the American Indian tribes and the involved Federal agencies to better understand what kinds of responses have been recorded and what kinds of places have elicited these responses. The following tribes participated in this study: Chemehuevi Indian Tribe, Colorado River Indian Tribe, Las Vegas Paiute Tribe, Moapa Band of Paiute Indians, Pahrump Paiute Tribe, Paiute Indian Tribe of Utah, and Southern Indian tribe.

Thèse numérisée par la Direction des bibliothèques de l'Université de Montréal.

Title: Project of Educational cycle trail in the Protected Landscape Area in Bohemian Karst Objective: The objective of this work was to create an Educational cycle trail in the Protected Landscape Area of the Bohemian Karst. The trail, natural and cultural attractions and other information process into guidebook which will be available at tourist information centers and on the Internet. Methods: Collecting and sorting information about the natural and cultural wealth of the region. Summarizing information in guidebook and creating a trail. Subsequent test the applicability of a booklet form of a questionnaire to a group of cyclists who created the route with the completed booklets. Results: The results of this work are two proposal of Educational cycle trail in the Protected Landscape Area of the Bohemian Karst, which are processed into guidebook that contains trail description, information about each trail and map material. The final form of the trail is also based on results of questionnaires and direct responses of testees. The guidebook can be offered to information centers in the area of Bohemian Karst or through them be available in electronic form on the Internet. Keywords: cycling, Educational trail, Protected Landscape Area, Bohemian Karst.

Title: Participants' satisfaction with Salomon Trail Running Cup 2014 sports event Objectives: The main aim of this diploma thesis is to analyse current level of customer satisfaction with sports event, find out their opinions and potential shortcomings in each running event by using questionnaire survey. Define any problem areas and suggest appropriate management recommendations by evaluating empirical data obtained from own market research. This would lead to improvement of runners' satisfaction with this sports event. Partial goal of this diploma thesis is to find potential coherence between customers' satisfaction and whether they attended Salomon Trail Running Cup for the first time or repeatedly. Methods: Quantitative questionnaire research was used to obtain data from respondents. Respondents were interviewed either in person or in writing. Informal interviews were made with the management of the sports event. T-test method was used to find potential coherence between customers' satisfaction and their attendance in the past Salomon Trail Running Cup events. Results: Marketing research showed that runners were mostly satisfied with this sports event. On the other hand several important problematic areas were discovered that management of this sports event should work on to fulfil runners'...

Title: The proposal of the Geological Trails in the Area of the Rychleby Mts. Abstract: This thesis is devoted to draft for new nature trails in the area of the Rychleby Mts. with a specific focus on geology. The proposed trails are preceded by detailed characteristics of geomorphology, geology and stratigraphy of the studied area. The trails are located in two areas, i. e. the northern part of the Rychleby Mts. (Račí údolí - Zálesí - Javorník) and Žulová highlands (Around Žulová pluton). The first mentioned trail is designed in two levels of difficulty for elementary and secondary schools. The trail are supplemented by specific guidebooks, worksheets and the "Didactic recommendation for teachers", which included general didactic recommendations, next detailed information about the trails and suggestions for other additional activities. The trails had been verified in practice on students, amateurs and experts. Anthe effectiveness of the trails was evaluated through surveys with participants. It has been proved that the trails are suitable complement of education process mainly for natural science and the trails are also useful for non-educational leisure activities for visitors of these areas. Key words: nature trail, the Rychleby Mts., excursion, pedagogical uses

Name A Project of Educational Bike Trail in Novohradske mountains Objective The aim of this work is to create project of Educational Bike Trail in Novohradske mountains and the associated creation of an information booklet for distribution of information centers in the region, creating web pages and also information boards via QR code. Methods In the first part of this work are collected and classified information processed form of research. There were used literature and internet resources. In the second part of the processed information is used to create information material to the cycling nature trail. This material was then validated questionnaire. Results The result of this work is to project the bike trail which includes the information brochure, the website, the trail's logo and information boards at each stop. These media contain all the educational information related to places along the route together with photographs and maps. Keywords Novohradske mountains, educational cycling, bicycle trail guide