Number Sequences in an Integral Form with a Generalized Convolution Property and Somos-4 Hankel Determinants

MSC 2010: 11B83, 05A19, 33C45

Role of epithelial Na+ channels in endothelial function

An increasing number of mechano-sensitive ion channels in endothelial cells have been identified in response to blood flow and hydrostatic pressure. However, how these channels respond to flow under different physiological and pathological conditions remains unknown. Our results show that epithelial Na+ channels (ENaCs) colocalize with hemeoxygenase-1 (HO-1) and hemeoxygenase-2 (HO-2) within the caveolae on the apical membrane of endothelial cells and are sensitive to stretch pressure and shear stress. ENaCs exhibited low levels of activity until their physiological environment was changed; in this case, the upregulation of HO-1, which in turn facilitated heme degradation and hence increased the carbon monoxide (CO) generation. CO potently increased the bioactivity of ENaCs, releasing the channel from inhibition. Endothelial cells responded to shear stress by increasing the Na+ influx rate. Elevation of intracellular Na+ concentration hampered the transportation of l-arginine, resulting in impaired nitric oxide (NO) generation. Our data suggest that ENaCs that are endogenous to human endothelial cells are mechano-sensitive. Persistent activation of ENaCs could inevitably lead to endothelium dysfunction and even vascular diseases such as atherosclerosis.

Studying Key Amino Acids in the Function of Ras Interference 1 (Rinl) SH2 and Vps9 Domains

Receptor mediated endocytosis effectively removes the "ears" with which a cell would "hear" a signal conveyed by extracellular signaling molecules, but does not necessarily block the signaling pathway in which the endocytosed receptor participates. In the process of signal attenuation, this newly formed vesicle is fused with a phagosome and the receptor molecules are degraded. Receptor mediated endocytosis as a way to attenuate epidermal growth factor (EGF) and insulin signaling will be the focus here. Ras Interference 1 (Rin 1) is a multifunctional protein involved in intracellular membrane trafficking and receptor mediated endocytosis through its Rab5 Guanine Exchange Factor and SH2 domains. The goal of this investigation is to determine the role of key amino acids involved in the interaction of Rinl with Epidermal Growth Factor Receptor and Rab5. To elucidate this role, a number of point mutations have been created and the effects of each mutation on Rin 1 function will be investigated. Key amino acids in the SH2 and Vps9 Domain were identified and effects of mutations on rate of endocytosis were observed.

Study of insulin-like growth factor signaling in mitochondrial function

Insulin-like Growth Factor-1 (IGF-1) signalling promotes cell growth and is associated with cancer progression, including metastasis, epithelial-mesenchymal transition (EMT), and resistance to therapy. Mitochondria play an essential role in cancer cell metabolism and accumulating evidence demonstrates that dysfunctional mitochondria associated with release of mitochondrial reactive oxygen species (ROS) can influence cancer cell phenotype and invasive potential. We previously isolated a mitochondrial UTP carrier (PNC1/SLC25A33) whose expression is regulated by IGF-1, and which is essential for mitochondrial maintenance. PNC1 suppression in cancer cells results in mitochondrial dysfunction and acquisition of a profound ROS-dependent invasive (EMT) phenotype. Moreover, over-expression of PNC1 in cancer cells that exhibit an EMT phenotype is sufficient to suppress mitochondrial ROS production and reverse the invasive phenotype. This led us to investigate the IGF-1-mitochondrial signalling axis in cancer cells. We found that IGF-1 signalling supports increased mitochondrial mass and Oxphos potential through a PI3K dependant pathway. Acute inhibition of IGF-1R activity with a tyrosine kinase inhibitor results in dysfunctional mitochondria and cell death. We also observed an adaptive response to IGF-1R inhibition upon prolonged exposure to the kinase inhibitor, where increased expression of the EGF receptor can compensate for loss of mitochondrial mass through activation of PI3K/mTOR signalling. However, these cells exhibit impaired mitochondrial biogenesis and mitophagy. We conclude that the IGF-1 is required for mitochondrial maintenance and biogenesis in cancer cells, and that pharmacological inhibition of this pathway may induce mitochondrial dysfunction and may render the cells more sensitive to glycolysis-targeted drugs.

The relationship between changes in cardiovascular function and changes in VO2peak following SIT

Background: It is well known that sprint interval training (SIT), induces significant increases in peak oxygen uptake (VO2peak) at the group level. However, there have been only a few studies that have addressed the variability of VO2peak response following SIT, and precise mechanism(s) that may explain individual magnitude of response are unknown. Purpose: Therefore, the purpose of this thesis was to: 1) examine the inter-individual variability of the VO2peak response following SIT, 2) to inspect the relationship between changes in both central and peripheral measures and changes in VO2peak, and 3) to assess if peripheral or central adaptations play a role in whether an individual is a high or low responder with respect to VO2peak. Subjects: Twenty-two young, recreationally active males (age: 20.4 1.7 years; weight: 78.4 10.2 kg; VO2peak: 3.7 0.62 L/min) Methods: VO2peak (L/min), peak cardiac output (Qpeak [L/min]), and peak deoxygenated hemoglobin (HHbpeak [mM]) were measured before and after 16 sessions of SIT (Tabata Protocol) over four weeks. Peak a-vO2diff was calculated using a derivation of the Fick equation. Results: Due to a systematic error, HHbpeak could not be used to differentiate between individual responses. There was a large range of VO2peak response from pre to post testing (-4.75 to 32.18% change) and there was a significant difference between the Low Response Group (LRG) (n=8) and the High Response Group (HRG) (n=8) [f(1, 14)= 64.27, p<0.001]. Furthermore, there was no correlation between delta () VO2peak and Qpeak (r=-0.18, p=0.46) for all participants, nor was there an interaction effect between the Low and High Response Groups [f(1,11)=0.572, p=0.47]. Lastly, there was a significant correlation between VO2peak and peak a-vO2diff [r=0.692, p<0.001], and a significant interaction effect with peak a-vO2diff [f(1, 14)= 13.27, p<0.004] when comparing the HRG to the LRG. Conclusions: There was inter-individual variability of VO2peak response following 4 weeks of SIT, but central adaptations did not influence this variation. This suggests that peripheral adaptations may be responsible for VO2peak adaptation.

Playing for Real: Designing Alternate Reality Games in Learning Contexts

Alternate Reality Game (ARG) represent a new genre of transmedia practice where players hunt for scattered clues, make sense of disparate information, and solve puzzles to advance an ever-evolving storyline. Players participate in ARGs using multiple communications technologies, ranging from print materials to mobile devices. However, many interaction design challenges must be addressed to weave these everyday communication tools together into an immersive, participatory experience. Transmedia design is not an everyday process. Designers must create and connect story bits across multiple media (video, audio, text) and multiple platforms (phones, computers, physical spaces). Furthermore, they must engage with players of varying skill levels. Few studies to-date have explored the design process of ARGs in learning contexts. Fewer still have focused on challenges involved in designing for youth (13-17 years old). In this study, I explore the process of designing ARGs as vehicles for promoting information literacy and participatory culture for adolescents (13-17 years old). Two ARG design scenarios, distinguished by target learning environment (formal and informal context) and target audience (adolescents), comprise the two cases that I examine. Through my analysis of these two design cases, I articulate several unique challenges faced by designers who create interactive, transmedia stories for – and with – youth. Drawing from these design challenges, I derive a repertoire of design strategies that future designers and researchers may use to create and implement ARGs for teens in learning contexts. In particular, I propose a narrative design framework that allows for the categorization of ARGs as storytelling constructs that lie along a continuum of participation and interaction. The framework can serve as an analytic tool for researchers and a guide for designers. In addition, I establish a framework of social roles that designers may employ to craft transmedia narratives before live launch and to promote and scaffold player participation after play begins. Overall, the contributions of my study include theoretical insights that may advance our understanding of narrative design and analysis as well as more practical design implications for designers and practitioners seeking to incorporate transmedia features into learning experiences that target youth.

The role of games in the development of oral skills in Teaching english as a foreign language to adult learners from An extension course at Universidad del Valle [recurso electr?nico]

This research arose from the notorious need to promote oral production in the adult learners of the English Extension courses at Universidad del Valle in 2014. This qualitative research was carried out in a 60 hour course divided along 15 sessions on Saturdays, and with an adult population between the ages of 22 and 65 years old. Its main objective was to describe the impact of games aimed at promoting oral production in English with a group of adult learners. Data were collected from one demographic survey, video-recordings of classroom events during the implementation of games, students? surveys after each game and a teacher?s journal. The analysis of data showed that games did have an impact in students? performance which was related to a positive atmosphere in the classroom. Students showed progress in terms of fluency, interaction and even pronunciation; however they still showed difficulties with accuracy in their spontaneous utterances. These learners? achievements seemed to have a relation with the class atmosphere during games where students showed high level of involvement, confidence, mutual support and enjoyment.

Orchid hybrids. Sander's complete list. Containing the names and parentages of all the known hybrid orchids whether introduced or artificially raised. Arranged in tabular, alphabetical form ...

Published originally as a supplement to the author's Orchid guide. cf. Naturae novitates, 28. Jahrg., 1906, p. 377.

Zika is not a reason for missing the Olympic Games in Rio de Janeiro: response to the open letter of Dr Attaran and colleagues to Dr Margaret Chan, Director - General, WHO, on the Zika threat to the Olympic and Paralympic Games

Attaran and colleagues in an open letter to WHO expressed their concern about the upcoming Olympic and Paralympic Games in Rio de Janeiro and the threat posed by the Zika epidemic (Attaran 2016). We agree that Zika virus is of great public health concern and much remains to be known about this disease. Care should be taken to reduce the risk of infection, especially to pregnant women. However, we argue that this is not sufficient reason for changing the original plans for the Games, in particular because of the time of the year when they will take place. The present article outlines several scientific results related to Zika and mosquito-borne infectious diseases dynamics that we believe ratify the current position of WHO in not endorsing the postponing or relocation of the 2016 Olympic and Paralympic Games (WHO 2016).

Development of two charge transfer complex spectrophotometric methods for determination of tofisopam in tablet dosage form

Purpose: To develop a simple, fast and sensitive spectrophotometric method for the determination of tofisopam in tablet dosage form. Methods: Tofisopam as n-electron donor was reacted with two π-acceptors, namely, chloranilic acid (ChA), and 7,7,8,8 tetracyanoquinodimethane (TCNQ) to form charge transfer complexes. The complexes were evaluated spectrophotometrically at 520 and 824 nm for ChA and TCNQ, respectively. The optimum conditions for the reaction were determined and optimized. The developed method was compared with Japanese Pharmacopeia method. Results: The calibration curve was linear in the ranges 25 – 125 and 30 – 150 μg/mL for ChA and TCNQ, respectively. The lower limit of detection was 8.0 and 10.0 μg/mL for ChA and TCNQ, respectively while the slope and intercept of the calibration curves were 0.0025 and 0.011 and 0.0115 and -0.237, for ChA and TCNQ, respectively. Conclusion: The developed methods for tofisopam have good accuracy and precision, and comparable to a standard pharmacopeial method. The methods can be applied for routine analysis and in quality control.

The relationship between changes in cardiovascular function and changes in VO2peak following SIT

Thesis (Master, Kinesiology & Health Studies) -- Queen's University, 2016-09-27 19:34:16.86

The role of inflammation in vascular function and pregnancy outcome in the pregnant stroke prone spontaneously hypertensive rat

During pregnancy, the maternal cardiovascular system undergoes major adaptation. One of these changes is a 40-50 % increase in circulating blood volume which requires a systemic remodelling of the vasculature in order to regulate maternal blood pressure and maximise blood supply to the developing placenta and fetus. These changes are broadly conserved between humans and rats making them an appropriate pre-clinical model in which to study the underlying mechanisms of pregnancy-dependent cardiovascular remodelling. Whilst women are normally protected against cardiovascular disease; pregnancy marks a period of time where women are susceptible to cardiovascular complications. Cardiovascular disease is the leading cause of maternal mortality in the United Kingdom; in particular hypertensive conditions are among the most common complications of pregnancy. One of the main underlying pathologies of these pregnancy complications is thought to be a failure of the maternal cardiovascular system to adapt. The remodelling of the uterine arteries, which directly supply the maternal-fetal interface, is paramount to a healthy pregnancy. Failure of the uterine arteries to remodel sufficiently can result in a number of obstetric complications such as preeclampsia, fetal growth restriction and spontaneous pregnancy loss. At present, it is poorly understood whether this deficient vascular response is due to a predisposition from existing maternal cardiovascular risk factors, the physiological changes that occur during pregnancy or a combination of both. Previous work in our group employed the stroke prone spontaneously hypertensive rat (SHRSP) as a model to investigate pregnancy-dependent remodelling of the uterine arteries. The SHRSP develops hypertension from 6 weeks of age and can be contrasted with the control strain, the Wistar Kyoto (WKY) rat. The phenotype of the SHRSP is therefore reflective of the clinical situation of maternal chronic hypertension during pregnancy. We showed that the SHRSP exhibited a deficient uterine artery remodelling response with respect to both structure and function accompanied by a reduction in litter size relative to the WKY at gestational day (GD) 18. A previous intervention study using nifedipine in the SHRSP achieved successful blood pressure reduction from 6 weeks of age and throughout pregnancy; however uterine artery remodelling and litter size at GD18 was not improved. We concluded that the abnormal uterine artery remodelling present in the SHRSP was independent of chronic hypertension. From these findings, we hypothesised that the SHRSP could be a novel model of spontaneously deficient uterine artery remodelling in response to pregnancy which was underpinned by other as yet unidentified cardiovascular risk factors. In Chapter 1 of this thesis, I have characterised the maternal, placental and fetal phenotype in pregnant (GD18) SHRSP and WKY. The pregnant SHRSP exhibit features of left ventricular hypertrophy in response to pregnancy and altered expression of maternal plasma biomarkers which have been previously associated with hypertension in human pregnancy. I developed a protocol for accurate dissection of the rat uteroplacental unit using qPCR probes specific for each layer. This allowed me to make an accurate and specific statement about gene expression in the SHRSP GD18 placenta; where oxidative stress related gene markers were increased in the vascular compartments. The majority of SHRSP placenta presented at GD18 with a blackened ring which encircled the tissue. Further investigation of the placenta using western blot for caspase 3 cleavage determined that this was likely due to increased cell death in the SHRSP placenta. The SHRSP also presented with a loss of one particular placental cell type at GD18: the glycogen cells. These cells could have been the target of cell death in the SHRSP placenta or were utilised early in pregnancy as a source of energy due to the deficient uterine artery blood supply. Blastocyst implantation was not altered but resorption rate was increased between SHRSP and WKY; indicating that the reduction in litter size in the SHRSP was primarily due to late (>GD14) pregnancy loss. Fetal growth was not restricted in SHRSP which led to the conclusion that SHRSP sacrifice part of their litter to deliver a smaller number of healthier pups. Activation of the immune system is a common pathway that has been implicated in the development of both hypertension and adverse pregnancy outcome. In Chapter 2, I proposed that this may be a mechanism of interest in SHRSP pregnancy and measured the pro-inflammatory cytokine, TNFα, as a marker of inflammation in pregnant SHRSP and WKY and in the placentas from these animals. TNFα was up-regulated in maternal plasma and urine from the GD18 SHRSP. In addition, TNFα release was increased from the GD18 SHRSP placenta as was the expression of the pro-inflammatory TNFα receptor 1 (Tnfr1). In order to investigate whether this excess TNFα was detrimental to SHRSP pregnancy, a vehicle-controlled intervention study using etanercept (a monoclonal antibody which works as a TNFα antagonist) was carried out. Etanercept treatment at GD0, 6, 12 and 18 resulted in an improvement in pregnancy outcome in the SHRSP with an increased litter size and reduced resorption rate. Furthermore, there was an improved uterine artery function in GD18 SHRSP treated with etanercept which was associated with an improved uterine artery blood flow over the course of gestation. In Chapter 3, I sought to identify the source of this detrimental excess of TNFα by designing a panel for maternal leukocytes in the blood and placenta at GD18. A population of CD3- CD161+ cells, which are defined as rat natural killer (NK) cells, were increased in number in the SHRSP. Intracellular flow cytometry also identified this cell type as a source of excess TNFα in blood and placenta from pregnant SHRSP. I then went on to evaluate the effects of etanercept treatment on these CD3- CD161+ cells and showed that etanercept reduced the expression of CD161 and the cytotoxic molecule, granzyme B, in the NK cells. Thus, etanercept limits the cytotoxicity and potential damaging effect of these NK cells in the SHRSP placenta. Analysing the urinary peptidome has clinical potential to identify novel pathways involved with disease and/or to develop biomarker panels to aid and stratify diagnosis. In Chapter 4, I utilised the SHRSP as a pre-clinical model to identify novel urinary peptides associated with hypertensive pregnancy. Firstly, a characterisation study was carried out in the kidney of the WKY and SHRSP. Urine samples from WKY and SHRSP taken at pre-pregnancy, mid-pregnancy (GD12) and late pregnancy (GD18) were used in the peptidomic screen. In order to capture peptides which were markers of hypertensive pregnancy from the urinary peptidomic data, I focussed on those that were only changed in a strain dependent manner at GD12 and 18 and not pre-pregnancy. Peptide fragments from the uromodulin protein were identified from this analysis to be increased in pregnant SHRSP relative to pregnant WKY. This increase in uromodulin was validated at the SHRSP kidney level using qPCR. Uromodulin has previously been identified to be a candidate molecule involved in systemic arterial hypertension but not in hypertensive pregnancy thus is a promising target for further study. In summary, we have characterised the SHRSP as the first model of maternal chronic hypertension during pregnancy and identified that inflammation mediated by TNFα and NK cells plays a key role in the pathology. The evidence presented in this thesis establishes the SHRSP as a pre-clinical model for pregnancy research and can be continued into clinical studies in pregnant women with chronic hypertension which remains an area of unmet research need.

Game Audio in Audio Games : Towards a Theory on the Roles and Functions of Sound in Audio Games

For the past few decades, researchers have increased our understanding of how sound functions within various audio–visual media formats. With a different focus in mind, this study aims to identify the roles and functions of sound in relation to the game form Audio Games, in order to explore the potential of sound when acting as an autonomous narrative form. Because this is still a relatively unexplored research field, the main purpose of this study is to help establish a theoretical ground and stimulate further research within the field of audio games. By adopting an interdisciplinary approach to the topic, this research relies on theoretical studies, examinations of audio games and contact with the audio game community. In order to reveal the roles of sound, the gathered data is analyzed according to both a contextual and a functional perspective. The research shows that a distinction between the terms ‘function’ and ‘role’ is important when analyzing sound in digital games. The analysis therefore results in the identification of two analytical levels that help define the functions and roles of an entity within a social context, named the Functional and the Interfunctional levels. In addition to successfully identifying three main roles of sound within audio games—each describing the relationship between sound and the entities game system, player and virtual environment—many other issues are also addressed. Consequently, and in accordance with its purpose, this study provides a broad foundation for further research of sound in both audio games and video games.

The impact of brand and product placements in electronic games

In an environment where it has become increasingly difficult to attract consumer attention, marketers have begun to explore alternative forms of marketing communication. One such form that has emerged is product placement, which has more recently appeared in electronic games. Given changes in media consumption and the growth of the games industry, it is not surprising that games are being exploited as a medium for promotional content. Other market developments are also facilitating and encouraging their use, in terms of both the insertion of brand messages into video games and the creation of brand-centred environments, labelled ‘advergames’. However, while there is much speculation concerning the beneficial outcomes for marketers, there remains a lack of academic work in this area and little empirical evidence of the actual effects of this form of promotion on game players. Only a handful of studies are evident in the literature, which have explored the influence of game placements on consumers. The majority have studied their effect on brand awareness, largely demonstrating that players can recall placed brands. Further, most research conducted to date has focused on computer and online games, but consoles represent the dominant platform for play (Taub, 2004). Finally, advergames have largely been neglected, particularly those in a console format. Widening the gap in the literature is the fact that insufficient academic attention has been given to product placement as a marketing communication strategy overall, and to games in general. The unique nature of the strategy also makes it difficult to apply existing literature to this context. To address a significant need for information in both the academic and business domains, the current research investigates the effects of brand and product placements in video games and advergames on consumer attitude to the brand and corporate image. It was conducted in two stages. Stage one represents a pilot study. It explored the effects of use simulated and peripheral placements in video games on players’ and observers’ attitudinal responses, and whether these are influenced by involvement with a product category or skill level in the game. The ability of gamers to recall placed brands was also examined. A laboratory experiment was employed with a small sample of sixty adult subjects drawn from an Australian east-coast university, some of who were exposed to a console video game on a television set. The major finding of study one is that placements in a video game have no effect on gamers’ attitudes, but they are recalled. For stage two of the research, a field experiment was conducted with a large, random sample of 350 student respondents to investigate the effects on players of brand and product placements in handheld video games and advergames. The constructs of brand attitude and corporate image were again tested, along with several potential confounds. Consistent with the pilot, the results demonstrate that product placement in electronic games has no effect on players’ brand attitudes or corporate image, even when allowing for their involvement with the product category, skill level in the game, or skill level in relation to the medium. Age and gender also have no impact. However, the more interactive a player perceives the game to be, the higher their attitude to the placed brand and corporate image of the brand manufacturer. In other words, when controlling for perceived interactivity, players experienced more favourable attitudes, but the effect was so weak it probably lacks practical significance. It is suggested that this result can be explained by the existence of excitation transfer, rather than any processing of placed brands. The current research provides strong, empirical evidence that brand and product placements in games do not produce strong attitudinal responses. It appears that the nature of the game medium, game playing experience and product placement impose constraints on gamer motivation, opportunity and ability to process these messages, thereby precluding their impact on attitude to the brand and corporate image. Since this is the first study to investigate the ability of video game and advergame placements to facilitate these deeper consumer responses, further research across different contexts is warranted. Nevertheless, the findings have important theoretical and managerial implications. This investigation makes a number of valuable contributions. First, it is relevant to current marketing practice and presents findings that can help guide promotional strategy decisions. It also presents a comprehensive review of the games industry and associated activities in the marketplace, relevant for marketing practitioners. Theoretically, it contributes new knowledge concerning product placement, including how it should be defined, its classification within the existing communications framework, its dimensions and effects. This is extended to include brand-centred entertainment. The thesis also presents the most comprehensive analysis available in the literature of how placements appear in games. In the consumer behaviour discipline, the research builds on theory concerning attitude formation, through application of MacInnis and Jaworski’s (1989) Integrative Attitude Formation Model. With regards to the games literature, the thesis provides a structured framework for the comparison of games with different media types; it advances understanding of the game medium, its characteristics and the game playing experience; and provides insight into console and handheld games specifically, as well as interactive environments generally. This study is the first to test the effects of interactivity in a game environment, and presents a modified scale that can be used as part of future research. Methodologically, it addresses the limitations of prior research through execution of a field experiment and observation with a large sample, making this the largest study of product placement in games available in the literature. Finally, the current thesis offers comprehensive recommendations that will provide structure and direction for future study in this important field.