GIS-Based Suitability Analysis and Planning of Green Infrastructure: A Case of the PPCOD, Capitol Hill

Thesis (Master's)--University of Washington, 2016-06

Hodgkin's lymphoma cell lines express a fusion protein encoded by intergenically spliced mRNA for the multilectin receptor DEC-205 (CD205) and a novel C-type lectin receptor DCL-1

Classic Hodgkin's lymphoma (HL) tissue contains a small population of morphologically distinct malignant cells called Hodgkin and Reed-Sternberg (HRS) cells, associated with the development of HL. Using 3'-rapid amplification of cDNA ends ( RACE) we identified an alternative mRNA for the DEC-205 multilectin receptor in the HRS cell line L428. Sequence analysis revealed that the mRNA encodes a fusion protein between DEC-205 and a novel C-type lectin DCL-1. Although the 7.5-kb DEC-205 and 4.2-kb DCL-1 mRNA were expressed independently in myeloid and B lymphoid cell lines, the DEC-205/DCL-1 fusion mRNA (9.5 kb) predominated in the HRS cell lines ( L428, KM-H2, and HDLM-2). The DEC-205 and DCL-1 genes comprising 35 and 6 exons, respectively, are juxtaposed on chromosome band 2q24 and separated by only 5.4 kb. We determined the DCL-1 transcription initiation site within the intervening sequence by 5'-RACE, confirming that DCL-1 is an independent gene. Two DEC-205/DCL-1 fusion mRNA variants may result from cotranscription of DEC-205 and DCL-1, followed by splicing DEC-205 exon 35 or 34-35 along with DCL-1 exon 1. The resulting reading frames encode the DEC-205 ectodomain plus the DCL-1 ectodomain, the transmembrane, and the cytoplasmic domain. Using DCL-1 cytoplasmic domain-specific polyclonal and DEC-205 monoclonal antibodies for immunoprecipitation/Western blot analysis, we showed that the fusion mRNA is translated into a DEC-205/DCL-1 fusion protein, expressed in the HRS cell lines. These results imply an unusual transcriptional control mechanism in HRS cells, which cotranscribe an mRNA containing DEC-205 and DCL-1 prior to generating the intergenically spliced mRNA to produce a DEC-205/DCL-1 fusion protein.

Analysis of oxidized and chlorinated lipids by mass spectrometry and relevance to signalling

Oxidized and chlorinated phospholipids are generated under inflammatory conditions and are increasingly understood to play important roles in diseases involving oxidative stress. MS is a sensitive and informative technique for monitoring phospholipid oxidation that can provide structural information and simultaneously detect a wide variety of oxidation products, including chain-shortened and -chlorinated phospholipids. MSn technologies involve fragmentation of the compounds to yield diagnostic fragment ions and thus assist in identification. Advanced methods such as neutral loss and precursor ion scanning can facilitate the analysis of specific oxidation products in complex biological samples. This is essential for determining the contributions of different phospholipid oxidation products in disease. While many pro-inflammatory signalling effects of oxPLs (oxidized phospholipids) have been reported, it has more recently become clear that they can also have anti-inflammatory effects in conditions such as infection and endotoxaemia. In contrast with free radical-generated oxPLs, the signalling effects of chlorinated lipids are much less well understood, but they appear to demonstrate mainly pro-inflammatory effects. Specific analysis of oxidized and chlorinated lipids and the determination of their molecular effects are crucial to understanding their role in disease pathology.

Extracting interactions between proteins from the literature

During the last decade, biomedicine has witnessed a tremendous development. Large amounts of experimental and computational biomedical data have been generated along with new discoveries, which are accompanied by an exponential increase in the number of biomedical publications describing these discoveries. In the meantime, there has been a great interest with scientific communities in text mining tools to find knowledge such as protein-protein interactions, which is most relevant and useful for specific analysis tasks. This paper provides a outline of the various information extraction methods in biomedical domain, especially for discovery of protein-protein interactions. It surveys methodologies involved in plain texts analyzing and processing, categorizes current work in biomedical information extraction, and provides examples of these methods. Challenges in the field are also presented and possible solutions are discussed.

From biomedical literature to knowledge:mining protein-protein interactions

To date, more than 16 million citations of published articles in biomedical domain are available in the MEDLINE database. These articles describe the new discoveries which accompany a tremendous development in biomedicine during the last decade. It is crucial for biomedical researchers to retrieve and mine some specific knowledge from the huge quantity of published articles with high efficiency. Researchers have been engaged in the development of text mining tools to find knowledge such as protein-protein interactions, which are most relevant and useful for specific analysis tasks. This chapter provides a road map to the various information extraction methods in biomedical domain, such as protein name recognition and discovery of protein-protein interactions. Disciplines involved in analyzing and processing unstructured-text are summarized. Current work in biomedical information extracting is categorized. Challenges in the field are also presented and possible solutions are discussed.

Self-explanation in adaptive systems based on runtime goal-based models

The behaviour of self adaptive systems can be emergent, which means that the system’s behaviour may be seen as unexpected by its customers and its developers. Therefore, a self-adaptive system needs to garner confidence in its customers and it also needs to resolve any surprise on the part of the developer during testing and maintenance. We believe that these two functions can only be achieved if a self-adaptive system is also capable of self-explanation. We argue a self-adaptive system’s behaviour needs to be explained in terms of satisfaction of its requirements. Since self-adaptive system requirements may themselves be emergent, we propose the use of goal-based requirements models at runtime to offer self-explanation of how a system is meeting its requirements. We demonstrate the analysis of run-time requirements models to yield a self-explanation codified in a domain specific language, and discuss possible future work.

Statistical dialog management for health interventions

Research endeavors on spoken dialogue systems in the 1990s and 2000s have led to the deployment of commercial spoken dialogue systems (SDS) in microdomains such as customer service automation, reservation/booking and question answering systems. Recent research in SDS has been focused on the development of applications in different domains (e.g. virtual counseling, personal coaches, social companions) which requires more sophistication than the previous generation of commercial SDS. The focus of this research project is the delivery of behavior change interventions based on the brief intervention counseling style via spoken dialogue systems. ^ Brief interventions (BI) are evidence-based, short, well structured, one-on-one counseling sessions. Many challenges are involved in delivering BIs to people in need, such as finding the time to administer them in busy doctors' offices, obtaining the extra training that helps staff become comfortable providing these interventions, and managing the cost of delivering the interventions. Fortunately, recent developments in spoken dialogue systems make the development of systems that can deliver brief interventions possible. ^ The overall objective of this research is to develop a data-driven, adaptable dialogue system for brief interventions for problematic drinking behavior, based on reinforcement learning methods. The implications of this research project includes, but are not limited to, assessing the feasibility of delivering structured brief health interventions with a data-driven spoken dialogue system. Furthermore, while the experimental system focuses on harmful alcohol drinking as a target behavior in this project, the produced knowledge and experience may also lead to implementation of similarly structured health interventions and assessments other than the alcohol domain (e.g. obesity, drug use, lack of exercise), using statistical machine learning approaches. ^ In addition to designing a dialog system, the semantic and emotional meanings of user utterances have high impact on interaction. To perform domain specific reasoning and recognize concepts in user utterances, a named-entity recognizer and an ontology are designed and evaluated. To understand affective information conveyed through text, lexicons and sentiment analysis module are developed and tested.^

ArchWiSeN: uma estratégia baseada em modelos para desenvolvimento de aplicações para redes de sensores e atuadores sem fio

Wireless Sensor and Actuator Networks (WSAN) are a key component in Ubiquitous Computing Systems and have many applications in different knowledge domains. Programming for such networks is very hard and requires developers to know the available sensor platforms specificities, increasing the learning curve for developing WSAN applications. In this work, an MDA (Model-Driven Architecture) approach for WSAN applications development called ArchWiSeN is proposed. The goal of such approach is to facilitate the development task by providing: (i) A WSAN domain-specific language, (ii) a methodology for WSAN application development; and (iii) an MDA infrastructure composed of several software artifacts (PIM, PSMs and transformations). ArchWiSeN allows the direct contribution of domain experts in the WSAN application development without the need of specialized knowledge on WSAN platforms and, at the same time, allows network experts to manage the application requirements without the need for specific knowledge of the application domain. Furthermore, this approach also aims to enable developers to express and validate functional and non-functional requirements of the application, incorporate services offered by WSAN middleware platforms and promote reuse of the developed software artifacts. In this sense, this Thesis proposes an approach that includes all WSAN development stages for current and emerging scenarios through the proposed MDA infrastructure. An evaluation of the proposal was performed by: (i) a proof of concept encompassing three different scenarios performed with the usage of the MDA infrastructure to describe the WSAN development process using the application engineering process, (ii) a controlled experiment to assess the use of the proposed approach compared to traditional method of WSAN application development, (iii) the analysis of ArchWiSeN support of middleware services to ensure that WSAN applications using such services can achieve their requirements ; and (iv) systematic analysis of ArchWiSeN in terms of desired characteristics for MDA tool when compared with other existing MDA tools for WSAN.

Characterisation of an ubiquitin binding CUE domain in presenilin-1

The presenilins are the catalytic component of the gamma-secretase protease complex, involved in the regulated intramembrane proteolysis of numerous type-1 transmembrane proteins, including Amyloid precursor protein (APP) and Notch. In addition to their role in the γ-secretase complex the presenilins are involved in a number of γ-secretase independent functions such as calcium homeostasis, apoptosis, inflammation and protein trafficking. Presenilin function is known to be regulated through posttranslational modifications like endoproteolysis, phosphorylation and ubiquitination. Using a bioinformatics and protein sequence analysis approach this lab has identified a putative ubiquitin binding CUE domain in the presenilins. The aim of this project was to characterise the function of the presenilin CUE domains. Firstly, the presenilins are shown to contain a functional ubiquitin-binding CUE domain that preferentially binds to K63-linked polyubiquitin chains. The PS1 CUE domain is shown to be dispensable for PS1 endoproteolysis and γ-secretase mediated cleavage of APP, Notch and IL-1R1. This suggests the PS1 CUE domain is involved in a γ-secretase independent PS1 function. Our hypothesis is that the PS1 CUE domain is involved in regulating PS1’s intermolecular protein-protein interactions or intramolecular PS1:PS1 interactions. Here the PS1 CUE domain is shown to be dispensable for the interaction of PS1 and the K63-linked polyubiquitinated PS1 interacting proteins P75NTR, IL-1R1, TRAF6, TRAF2 and RIP1. To further investigate PS1 CUE domain function a mass spectrometry proteomics based approach is used to identify PS1 CUE domain interacting proteins. This proteomics approach demonstrated that the PS1 CUE domain is not required for PS1 dimerization. Instead a number of proteins thatinteract with the PS1 CUE domain are identified as well as proteins whose interaction with PS1 is downregulated by the presence of the PS1 CUE domain. Bioinformatic analysis of these proteins suggests possible roles for the PS1 CUE domain in regulating cell signalling, ubiquitination or cellular trafficking.

Statistical Dialog Management for Health Interventions

Research endeavors on spoken dialogue systems in the 1990s and 2000s have led to the deployment of commercial spoken dialogue systems (SDS) in microdomains such as customer service automation, reservation/booking and question answering systems. Recent research in SDS has been focused on the development of applications in different domains (e.g. virtual counseling, personal coaches, social companions) which requires more sophistication than the previous generation of commercial SDS. The focus of this research project is the delivery of behavior change interventions based on the brief intervention counseling style via spoken dialogue systems. Brief interventions (BI) are evidence-based, short, well structured, one-on-one counseling sessions. Many challenges are involved in delivering BIs to people in need, such as finding the time to administer them in busy doctors' offices, obtaining the extra training that helps staff become comfortable providing these interventions, and managing the cost of delivering the interventions. Fortunately, recent developments in spoken dialogue systems make the development of systems that can deliver brief interventions possible. The overall objective of this research is to develop a data-driven, adaptable dialogue system for brief interventions for problematic drinking behavior, based on reinforcement learning methods. The implications of this research project includes, but are not limited to, assessing the feasibility of delivering structured brief health interventions with a data-driven spoken dialogue system. Furthermore, while the experimental system focuses on harmful alcohol drinking as a target behavior in this project, the produced knowledge and experience may also lead to implementation of similarly structured health interventions and assessments other than the alcohol domain (e.g. obesity, drug use, lack of exercise), using statistical machine learning approaches. In addition to designing a dialog system, the semantic and emotional meanings of user utterances have high impact on interaction. To perform domain specific reasoning and recognize concepts in user utterances, a named-entity recognizer and an ontology are designed and evaluated. To understand affective information conveyed through text, lexicons and sentiment analysis module are developed and tested.

Correlation between anxiety and academic self-concept in interpreter trainees

This paper focuses on two basic issues: the anxiety-generating nature of the interpreting task and the relevance of interpreter trainees’ academic self-concept. The first has already been acknowledged, although not extensively researched, in several papers, and the second has only been mentioned briefly in interpreting literature. This study seeks to examine the relationship between the anxiety and academic self-concept constructs among interpreter trainees. An adapted version of the Foreign Language Anxiety Scale (Horwitz et al., 1986), the Academic Autoconcept Scale (Schmidt, Messoulam & Molina, 2008) and a background information questionnaire were used to collect data. Students’ t-Test analysis results indicated that female students reported experiencing significantly higher levels of anxiety than male students. No significant gender difference in self-concept levels was found. Correlation analysis results suggested, on the one hand, that younger would-be interpreters suffered from higher anxiety levels and students with higher marks tended to have lower anxiety levels; and, on the other hand, that younger students had lower self-concept levels and higher-ability students held higher self-concept levels. In addition, the results revealed that students with higher anxiety levels tended to have lower self-concept levels. Based on these findings, recommendations for interpreting pedagogy are discussed.

Tacit knowledge sharing: the determination of a methodological approach to explore the intangible.

Introduction. Research design should take into account both (a) the specific nature of the object under scrutiny, and (b) approaches to its study in the past. This is to ensure that informed decisions are made regarding research design in future empirical studies. Here these factors are taken into account with reference to methodological choice for a doctoral study on tacit knowledge sharing, and the extent to tacit knowledge sharing may be facilitated by online tools. The larger study responds to calls for the two domains of knowledge management and human information behaviour to be considered together in terms of their research approaches and theory development. Method. Relevant literature – both domain-specific (knowledge management) and general (research methods in social science) - was identified and analysed to identify the most appropriate approaches for an empirical study of tacit knowledge sharing. Analysis. The analysis shows that there are a number of challenges associated with studying an intangible entity such as tacit knowledge. Quantitative, qualitative and mixed methods have been adopted in prior work on this theme, each with their own strengths and weaknesses. Results. The analysis has informed a decision to adopt a research approach that deploys mixed methods for an inductive case study to extend knowledge of the influence of online tools on tacit knowledge sharing. Conclusion. This work intends to open the debate on methodological choice and routes to implementation for studies that are subject to practical constraints imposed by the context in which they are situated.

Age and gender differences in the relation between self-concept facets and self-esteem

This study tested whether the gender intensification hypothesis applies to relations between multiple domain-specific self-concept facets and self-esteem. This hypothesis predicts gender-stereotypic differences in these relations and assumes they intensify with age. Furthermore, knowledge about gender-related or age-related differences in self-concept-self-esteem relations might provide valuable knowledge for designing effective self-esteem enhancement interventions. We investigated grade and gender differences in the relations between domain-specific self-concept facets and self-esteem within a sample of 1958 German students in Grades 3 to 6. Results indicated no difference in the self-concept - self-esteem relations between the subsamples of third and fourth graders and fifth and sixth graders or between boys and girls. These relations also did not differ between boys and girls in the subsamples of third and fourth graders and fifth and sixth graders. These results suggest self-concept-self-esteem relations to be invariant across grade levels and gender and thus did not support the gender intensification hypothesis.

Robot-assisted laparoscopic prostatectomy versus open radical retropubic prostatectomy: early outcomes from a randomised controlled phase 3 study

BACKGROUND: The absence of trial data comparing robot-assisted laparoscopic prostatectomy and open radical retropubic prostatectomy is a crucial knowledge gap in uro-oncology. We aimed to compare these two approaches in terms of functional and oncological outcomes and report the early postoperative outcomes at 12 weeks. METHOD: In this randomised controlled phase 3 study, men who had newly diagnosed clinically localised prostate cancer and who had chosen surgery as their treatment approach, were able to read and speak English, had no previous history of head injury, dementia, or psychiatric illness or no other concurrent cancer, had an estimated life expectancy of 10 years or more, and were aged between 35 years and 70 years were eligible and recruited from the Royal Brisbane and Women's Hospital (Brisbane, QLD). Participants were randomly assigned (1:1) to receive either robot-assisted laparoscopic prostatectomy or radical retropubic prostatectomy. Randomisation was computer generated and occurred in blocks of ten. This was an open trial; however, study investigators involved in data analysis were masked to each patient's condition. Further, a masked central pathologist reviewed the biopsy and radical prostatectomy specimens. Primary outcomes were urinary function (urinary domain of EPIC) and sexual function (sexual domain of EPIC and IIEF) at 6 weeks, 12 weeks, and 24 months and oncological outcome (positive surgical margin status and biochemical and imaging evidence of progression at 24 months). The trial was powered to assess health-related and domain-specific quality of life outcomes over 24 months. We report here the early outcomes at 6 weeks and 12 weeks. The per-protocol populations were included in the primary and safety analyses. This trial was registered with the Australian New Zealand Clinical Trials Registry (ANZCTR), number ACTRN12611000661976. FINDINGS: Between Aug 23, 2010, and Nov 25, 2014, 326 men were enrolled, of whom 163 were randomly assigned to radical retropubic prostatectomy and 163 to robot-assisted laparoscopic prostatectomy. 18 withdrew (12 assigned to radical retropubic prostatectomy and six assigned to robot-assisted laparoscopic prostatectomy); thus, 151 in the radical retropubic prostatectomy group proceeded to surgery and 157 in the robot-assisted laparoscopic prostatectomy group. 121 assigned to radical retropubic prostatectomy completed the 12 week questionnaire versus 131 assigned to robot-assisted laparoscopic prostatectomy. Urinary function scores did not differ significantly between the radical retropubic prostatectomy group and robot-assisted laparoscopic prostatectomy group at 6 weeks post-surgery (74·50 vs 71·10; p=0·09) or 12 weeks post-surgery (83·80 vs 82·50; p=0·48). Sexual function scores did not differ significantly between the radical retropubic prostatectomy group and robot-assisted laparoscopic prostatectomy group at 6 weeks post-surgery (30·70 vs 32·70; p=0·45) or 12 weeks post-surgery (35·00 vs 38·90; p=0·18). Equivalence testing on the difference between the proportion of positive surgical margins between the two groups (15 [10%] in the radical retropubic prostatectomy group vs 23 [15%] in the robot-assisted laparoscopic prostatectomy group) showed that equality between the two techniques could not be established based on a 90% CI with a Δ of 10%. However, a superiority test showed that the two proportions were not significantly different (p=0·21). 14 patients (9%) in the radical retropubic prostatectomy group versus six (4%) in the robot-assisted laparoscopic prostatectomy group had postoperative complications (p=0·052). 12 (8%) men receiving radical retropubic prostatectomy and three (2%) men receiving robot-assisted laparoscopic prostatectomy experienced intraoperative adverse events. INTERPRETATION: These two techniques yield similar functional outcomes at 12 weeks. Longer term follow-up is needed. In the interim, we encourage patients to choose an experienced surgeon they trust and with whom they have rapport, rather than a specific surgical approach. FUNDING: Cancer Council Queensland.

Un modèle rétroactif de réconciliation utilité-confidentialité sur les données d’assurance

Le partage des données de façon confidentielle préoccupe un bon nombre d’acteurs, peu importe le domaine. La recherche évolue rapidement, mais le manque de solutions adaptées à la réalité d’une entreprise freine l’adoption de bonnes pratiques d’affaires quant à la protection des renseignements sensibles. Nous proposons dans ce mémoire une solution modulaire, évolutive et complète nommée PEPS, paramétrée pour une utilisation dans le domaine de l’assurance. Nous évaluons le cycle entier d’un partage confidentiel, de la gestion des données à la divulgation, en passant par la gestion des forces externes et l’anonymisation. PEPS se démarque du fait qu’il utilise la contextualisation du problème rencontré et l’information propre au domaine afin de s’ajuster et de maximiser l’utilisation de l’ensemble anonymisé. À cette fin, nous présentons un algorithme d’anonymat fortement contextualisé ainsi que des mesures de performances ajustées aux analyses d’expérience.