Η Κινάση του Αναπλαστικού Λεμφώματος(Alk) είναι ένας υποδοχέας κινάσης τυροσίνης(RTK)ο οποίος εμπλέκεται σε διάφορες μορφές καρκίνου στον άνθρωπο, και η λειτουργικότητά του δεν έχει διαλευκανθεί πλήρως. Γνωρίζουμε ότι, ο υποδοχέας dAlk εκφράζεται ευρέως στο ΚΝΣ των ενήλικων μυγών και ιδιαίτερα στα μισχοειδή σωμάτια της Drosophila melanogaster, νευρωνικές δομές απαραίτητες για τις διεργασίες της μνήμης και της μάθησης. Στόχος της διπλωματικής εργασίας είναι η διερεύνηση του ρόλου του υποδοχέα dAlk και του προσδέτη του Jeb στην μνήμη μακράς διαρκείας(LTM)και ο καθορισμός του υποσυνόλου των νευρώνων στους οποίους παράγεται τόσο το Alk όσο και ο προσδέτης του Jeb. Για την διεξαγωγή των πειραμάτων χρησιμοποιήθηκαν γενετικές μέθοδοι και συμπεριφορικές μελέτες στην Drosophila melanogaster. / The Receptor Tyrosine Kinase Alk is implicated in several human cancers, but with many unknown functions.It has already been demonstrated that the receptor Alk is widely expressed in the central nervous system of adult flies and especially in the Mushroom Bodies, neuronal structures essential for learning and memory. The main purpose of my undergraduate thesis is to elucidate the role of the receptor Alk and its ligand Jeb in Long Term Memory. Moreover, we focused on finding the specific subset of neurons in which the RTK dAlk and its ligand Jeb are produced.For this research we used genetic tools alongwith behavioural techniques.

If international agreements regarding the need to significantly reduce greenhouse gas emissions are to be met then there is a high probability that the shipping industry will have to reduce its greenhouse gas emissions. For emission reductions from ships greater than around 40% then alternatives to fossil fuels - such as nuclear energy - will very likely be required. Whilst nuclear powered ships have successfully operated at sea for a number of decades, these have been primarily naval systems (or derivatives of naval systems such as icebreakers) and a few demonstration projects using reactors with low power outputs. The operational requirement for large civilian vessels (for example high capacity factors and limited personnel) mean the naval and past demonstration reactor systems are ill-suited for use in the current fleet of commercial container ships. There have been relatively few studies performed addressing the likely requirements upon core design a marine reactor would have to meet. This study addresses those issues and also implements a Pressurised Water Reactor core design capable of achieving these requirements. Furthermore, in order to simplify reactor operation for a limited number of personnel on board, the chemical reactivity control system has been eliminated during power operation. This has resulted in a novel low power density core that does not require refuelling for 15 years. The neutronic and fuel performance behaviour of this system has been studied with conventional UO2 fuel and thorium-uranium oxide ((Th,U)O2) fuel. With respect to (Th,U)O2 fuel there has been limited analysis comparing the performance of key fuel characteristics, such as fission gas release and thermal conductivity, as a function of uranium content in (Th,U)O2 fuel and their impact on fuel behaviour. Furthermore, the performance of neutronic codes for modelling Th-232 and U-233 from a variety of experiments using modern nuclear data libraries (post 1990) is lacking. Both of these issues are addressed in this study. Whilst it is frequently stated that thorium-based oxide fuel is superior to UO2 fuel it was found that due to the sensitivity of thermal conductivity on temperature and uranium content this was not true for the core designed in this study. The (Th,U)O2 core showed no net economic benefits with respect to the UO2 core and it was found that the fuel performance of (Th,U)O2 fuel was worse than the UO2 fuel in the reactor designed here. The UO2 core design, however, was able to satisfactorily meet the majority of requirements placed upon the system.

BACKGROUND: Guidelines recommend long-term treatment for opioid use disorder including the use of buprenorphine; however, little is known about patients in long-term treatment. OBJECTIVE: Examine the prevalence and patient characteristics associated with long-term treatment retention (≥1 year) in an Office Based Opioid Treatment (OBOT) program with buprenorphine. Study Design: This is a 12-year retrospective cohort study of adults on buprenorphine in OBOT in a large urban safety-net primary care practice. METHODS: The primary outcome was retention in OBOT for ≥1 continuous year. Patients who re-enrolled multiple times in the program contributed repeated observations. Potential predictors of ≥1 year retention assessed were: age, race/ethnicity, psychiatric diagnoses, hepatitis C, employment, prior buprenorphine, ever heroin use, current cocaine, benzodiazepine and alcohol use on enrollment. Factors associated with ≥1 year OBOT retention were identified using generalized estimating equation logistic regression models. The different reasons for clinic disengagement by retention status (i.e. ≥1 year vs. <1 year) were also described. RESULTS: OBOT treatment periods (n=1605) among 1237 patients were assessed. Almost half, 44.7% (717/1605), of all treatment periods were ≥1 year and a majority, 53.7% (664/1237), of patients had at least one ≥ 1 year period. In adjusted analyses, female gender (Adjusted Odds Ratio [AOR] 1.55, 95% CI [1.20, 2.00]) psychiatric diagnosis (AOR 1.75 [1.35, 2.27]) and age (AOR 1.19 per 10 year increase [1.05, 1.34]) were associated with greater odds of ≥1 year retention. Unemployment (AOR 0.72 [0.56, 0.92]), Hepatitis C (AOR 0.59 [0.45, 0.76]), black race/ethnicity (AOR 0.53 [0.36, 0.78]) and Hispanic race/ethnicity (AOR 0.66 [0.48, 0.92]), compared to white, were associated with lower odds of ≥1 year retention. Relapse to substance use appeared to be a less common reason for disengagement for the ≥1 year (23.3%) compared to the <1 year (40.1%) treatment periods. CONCLUSIONS: Over half of patients were successfully retained in Office Based Opioid Treatment with buprenorphine for ≥1 year. However, significant disparities in one-year treatment retention were seen, including poorer retention for patients who were younger, black, Hispanic, unemployed, or with hepatitis C. / 2018-11-09T00:00:00Z

Adolescent (14-17 year-olds) and young adult (18-20 year-olds) women account for a disproportionate 20% of the total number of unintended pregnancies that occur among women of all reproductive ages (14-55 year-olds) each year in the US. Nearly half (41%) of all unintended pregnancies result from the 18% of women who report inconsistent, incorrect, or no use of their contraceptive method. Evidence shows that a large proportion of these young women, especially those who are sexually active, come to the emergency department for their core sexual and reproductive health care needs. By obtaining a better understanding of the sexual and reproductive health needs and preferences of an urban population that is disproportionately low income and ethnically and racially diverse, our hope is to maximize adolescent and young adult accessibility to contraceptive services most feasible in the PED environment such as Nexplanon, in addition to the provision of comprehensive contraceptive counseling and education. OBJECTIVES: The first objective of this subgroup analysis is to determine the percentage of adolescent and young adult females presenting to an urban PED who are familiar with Nexplanon and to describe the demographic, sexual health, and contraceptive use characteristics of these young women. The second main objective of our study is to evaluate the sources of Nexplanon-related information reported by respondents familiar with Nexplanon. In addition to the main objectives, we also determine participant willingness to initiate or switch to Nexplanon® and receptivity to learning about contraceptive methods during a related or nonrelated visit to the PED. METHODS: This is a cross-sectional descriptive study using a paper-based anonymous questionnaire distributed to female patients, ages 16-21 years, presenting to a Boston urban pediatric emergency department (PED). This is a sub-group analysis of a larger study aimed at describing the contraceptive use history of young women who present to the PED. To identify if any statistically significant categorical variables existed between the two assigned groups, univariate analysis was performed using Chi-squared tests. Odds ratios with 95% confidence intervals (CIs) were obtained for the relationship between participants who have heard of Nexplanon and the three statistically significant variables: history of STDs, gravidity, and prior sexual intercourse with a male. Mean and Standard Deviation were used to describe the one continuous variable, age, followed by univariate analysis using independent t-test. Statistical significance was indicated using p-values for the categorical variables and odds ratio with 95% CI for the continuous variable—age. RESULTS: Of the 366 adolescent and young adult females included in our subgroup analysis, 230 (62.8%) indicated they were familiar with Nexplanon. We found that female participants familiar with Nexplanon were 1.3 times more likely to have had a prior STI, twice as likely to have had one or more previous pregnancies, and 3.5 times more likely to have previously engaged in sexual intercourse with a male compared to those female participants unfamiliar with Nexplanon. We also found that most (42.2%) female participants familiar with Nexplanon obtained their contraceptive information from their family and friends only, while about a third obtained their contraceptive information from medical professionals only. Among our total population of respondents, 6% (22/366) of our sub-group participants identified the contraceptive implant as their current method of contraception. Lastly, approximately 21% of female participants familiar with Nexplanon indicated current use of a long-acting reversible contraceptive method at the time of the survey. CONCLUSION: Overall, our study findings are supportive of and consistent with the provision and education of Nexplanon in the PED. This would be a crucial opportunity to provide comprehensive contraceptive counseling and convenient access to the most effective method of contraception among a population that disproportionately affected by unintended pregnancy. This can be made possible by enabling PED health care providers with the proper access to and training in Nexplanon. By adapting these patient-centered practices and techniques, the PED setting can contribute to the notable reduction in teen pregnancy seen in a variety of similar clinic-based interventions. The PED atmosphere has enormous potential to serve young women as an additional venue for contraception education and access.

Sonic hedgehog (Shh) is an important signalling protein expressed extensively in development, throughout tissues of the central nervous system, gut and the posterior of the limb bud. The complicated expression pattern of Shh is regulated by a series of long-range enhancers located flanking and dispersed throughout a 1 Mb genomic desert. Disruption of SHH as a result of mutations within the gene or its enhancers has been implicated in two developmental conditions. These are Holoproencephaly (HPE3) a common developmental defect of the forebrain and frequently the mid-face in humans, and preaxial polydactyly (PPD), a congenital limb abnormality encompassing a varied phenotype affecting the digits on the anterior side of the hands and feet that has been attributed to misexpression of Shh. In order to investigate the Shh regulatory landscape and survey regulatory activity, a transposon-based chromosomal engineering strategy known as the local hopping enhancer detection (LHED) system was employed. Using this method a targeting vector containing a LacZ reporter gene as well as LoxP sites was inserted within the Shh region. The ‘hopping’ nature of the transposable element was then exploited to scatter it throughout the region. Tetraploid complementation embryos derived entirely from ES cells were generated and examined in order to gain an insight into enhancer activity. The region was found to be in an open conformation over its length and is generally susceptible to all Shh enhancers. Genes within the regulatory domain, such as the widely expressed Rnf32 gene, were found to resist Shh enhancer activities by a process of regulatory evasion by the promoter, a mechanism that may be common in large regulatory domains. Finally, at the boundaries of the region Shh activity was found to be lost incrementally at a number of genomic positions. Mouse lines were also generated to look at both enhancer activity and loss of function effects and three deletions of increasing size were generated between Shh and the furthest enhancer, the Zrs. These in turn, delete firstly a gut and pharyngeal epithelial enhancer, secondly the gut, pharyngeal enhancers as well an oral epithelial enhancer and finally all three epithelial enhancers as well as three forebrain enhancers. Reporter gene expression was found to be lost incrementally from those enhancers deleted without disrupting the rest of the region. Previously unidentified notochord enhancer(s) were found to lie within the region 100-530 kb upstream of Shh. Examination of the resultant phenotypes showed that gut and craniofacial defects were found to occur as a result of the loss of enhancers which drive expression within these tissues. Variable phenotypes were found to occur potentially as a result of temporal changes to Shh expression or as a result of threshold levels of HH being required for normal development. Other enhancers within the Shh region and outwith the deletions were not found to be disrupted by these modifications suggesting the enhancers within the region act independently of each other. The largest deletion resulted in bringing the Zrs (which drives Shh limb expression) within 170 kb of the gene, however limb development; was not, found to be affected suggesting distance is not required for Zrs function. Overall, the LHED transposon system has been utilised in order to examine the Shh region in more detail, allowing mapping of enhancer function by reporter gene expression and examination of phenotypes generated by deletion of enhancers.

The motivation of this thesis is to provide a basic framework for treating long-range cross-correlated processes while keeping the methodology and as- sumptions as general as possible. Starting from the definition of long-range cross-correlated processes as jointly stationary processes with asymptotically power-law decaying cross-correlation function, we show that such definition implies a divergent at origin cross-power spectrum and power-law scaling of covariances of partial sums of the long-range cross-correlated processes. Chap- ter 2 describes these and other basic definitions and propositions together with necessary proofs. Chapter 3 then introduces several processes which possess long-range cross-correlated series properties. Apart from cases when the mem- ory parameter of the bivariate memory is a simple average of the parameters of the separate processes, we also introduce a new kind of process, which we call the mixed-correlated ARFIMA, which allows to control for both the bi- variate and univariate memory parameters. Chapter 4 deals with tests for a presence of long-range cross-correlations. We develop three new tests, and Monte-Carlo-simulation-based statistical power and size of the tests are com- pared. The newly introduced tests strongly surpass the already existing one. In Chapter 5,...

PART1, TITLE: A p53-inducible long non-coding RNA PICART1 mediating cancer cell proliferation and migration. Long non-coding RNAs (lncRNAs) function in the development and progression of cancer, but only a small portion of lncRNAs are characterized thus far. A novel lncRNA transcript with 2.53 kb in length was identified by a transcriptome sequencing analysis, named p53-inducible cancer-associated RNA transcript 1 (PICART1). This PICART1 is upregulated by p53 through a p53-binding site at -1808 to -1783bp. In breast and colorectal cancer cells and tissues, PICART1 expression was decreased. Ectopic expression of the PICART1 suppressed growth, proliferation, migration, and invasion of MCF7, MDA-MB-231 and HCT116 cells whereas silencing of PICART1 stimulated the cell growth and migration. In these cells, the expression of PICART1 lowered down the levels of p-AKT (Thr308 & Ser473) and p-GSK3β (Ser9), and accordingly, β-catenin, cyclin D1 and c-Myc expression were decreased, but p21cip1/Waf1 expression was increased. Together these data suggest that PICART1 is a novel p53-inducible tumor suppressor lncRNA, functioning through the AKT/GSK3β/β-catenin signaling cascade. PART2, TITLE: The novel long non-coding RNA PANCR is a tumor suppressor gene in breast cancer. Long non-coding RNAs (lncRNAs) function as oncogenes or tumor suppressors in development and progression of cancer. Chromosome 16q22.1 region is frequently deleted in breast cancer, which may contribute to breast carcinogenesis by inactivation of tumor suppressor genes. This study characterized a new lncRNA tumor suppressor, named p53 activating non-coding RNA (PANCR), located in this Chromosome 16q22.1 region. This PANCR lncRNA consists of 1.5kb in length. Our data showed that PANCR was downregulated in breast cancer tissues and cell lines. In the breast cancer cell lines, PANCR expression appeared reversely correlated with cell malignancy, and in breast cancer tissues, PANCR was downregulated over 2 times in 31 (62.0%) of 50 cases when compared to adjacent normal breast tissues. In breast cancer cells MCF7 cells, ectopic expression of PANCR suppressed cell proliferation in culture, but in contrast, shRNA–mediated silencing of PANCR promoted cell growth and proliferation.

Long-wavelength magnetic anomalies (LWMA) are broad scale magnetic fields that are usually observed at satellite altitudes. The origin of these fields have been assumed to be solely from the crust, disregarding possible contributions from the upper mantle. Using data from magnetic mantle xenoliths, the possible mantle contribution to LWMA was investigated for different regions including Siberian craton, Kamchatka subduction zone fore-arc, Hawaii hotspot, and French Massif Central plume. To do this, a MATLAB-based forward-modeling of magnetic anomalies from tectonic regions with different upper mantle geotherms and magnetized mantle geometries was developed. This model incorporated the increase in Curie temperature of magnetite with pressure, the current geotherms of the specific regions, and the statistical distributions of magnetic data from xenoliths in the specific regions. A Monte-Carlo method of random selection of values and repeated calculations was utilized in constraining the range of potential mantle contributions to satellite-observable LWMA. The Siberian craton shows the highest possible contribution to satellite magnetic anomalies with amplitudes ranging from 2 nT to 9 nT, with a wavelength equivalent to the long-axis of the craton. The Hawaii hotspot region displays a significant contribution of its upper mantle to satellite measured magnetic anomalies with an amplitude of the order of 2 nT, while the Massif Central plume regions shows an insignificant contribution of its upper mantle to satellite magnetic anomalies with potential total magnetic anomaly amplitude of 0.07 nT. Finally, the mantle portion of Kamchatka subduction zone shows a sizeable contribution to magnetic anomalies measurable at satellite altitude with an amplitude up to 1.3 nT. These results when compared with lithospheric total field intensity model derived from SWARM satellite data, show that the upper mantle can contribute significantly to LWMA depending on (a) the average remanent magnetization in xenoliths from such regions, (b) the thickness of magnetized mantle, and (c) the size of the region under consideration.

xiii, 163 p. : ill. (some col.) A print copy of this title is available through the UO Libraries under the call number: KNIGHT QP360.5 .B79 2008 / The ability to rapidly change from one course of action to another, i.e. "flexible behavior", is a hallmark of human cognition. Laboratory observations of switch costs, an increase in reaction time and errors when alternating between tasks compared to repeating a task, have been argued to be a measure of endogenous control during flexible behavior. However, alternative models suggest no such reconfiguration processes are necessary to account for performance in these task-switching situations. The first part of this dissertation uses neuroimaging to address whether reconfiguration processes do in fact occur in the explicit cuing variant of the task-switching paradigm. Using a 4:2 mapping between cues and tasks, we found neuroanatomical evidence for a dissociation between cue-switch (left prefrontal and lateral parietal) and task-switch (medial precuneus and cerebellar) related areas, consistent with the claim of endogenous control during task selection. The second portion explores whether automatic, long-term memory (LTM) processes can explain the "switch cost asymmetry", the fact that switch costs are larger when switching into a dominant task rather than into a competing non-dominant task. We modified an alternating runs task-switching paradigm to include either long or short response-to-stimulus intervals (RSIs) after each pair of trials (i.e., AA-AA-BB-BB), thereby inducing selection costs not only at the point of a task-switch (i.e., AA-BB), but also between same-task pairs (i.e., AA-AA). Using spatially compatible versus incompatible response rules and Stroop word versus color naming, we found asymmetric effects not only at task-change transitions, but also at task-repeat transitions when the RSI was long (presumably inducing frequent losses of task set). In two additional experiments, an asymmetry for long RSIs was obtained even when competing tasks were separated into alternating single task blocks, but not when the tasks were compared in a between-subject design. This pattern supports the idea that the asymmetry arises from interference effects occurring in LTM traces. The combined results of this dissertation characterize task-switching processes not as an "either-or" phenomenon in regards to the question of control, but rather as the interplay between top-down, executive functions and bottom-up, long-term memory priming mechanisms. / Adviser: Ulrich Mayr

Visual long term memory (VLTM) research has shown that we are capable of learning a virtually infinite amount of visual information. At the same time, visual short term memory (VSTM) research has shown that there is a severe limitation in the amount of information we can simultaneously apprehend at a given time. How does the severe capacity limitation in the initial uptake of information influence the encoding of information into VLTM? To this date, there has been no direct test of such influence, and the effect of such limitation has been unclear. Here, we demonstrate that, across wide varieties of conditions, the severe-capacity limitation in VSTM dictates the encoding of information into VLTM by determining the "bandwidth" of information transfer. This finding has a substantial implication for the understanding of the role of severely-capacity limited VSTM in forming many types of VLTM representations. / 10000-01-01