Serious games for energy social science research

This paper proposes a set of criteria for evaluation of serious games (SGs) which are intended as effective methods of engaging energy users and lowering consumption. We discuss opportunities for using SGs in energy research which go beyond existing feedback mechanisms, including use of immersive virtual worlds for learning and testing behaviours, and sparking conversations within households. From a review of existing SG evaluation criteria, we define a tailored set of criteria for energy SG development and evaluation. The criteria emphasise the need for the game to increase energy literacy through applicability to real-life energy use/management; clear, actionable goals and feedback; ways of comparing usage socially and personal relevance. Three existing energy games are evaluated according to this framework. The paper concludes by outlining directions for future development of SGs as an effective tool in social science research, including games which inspire reflection on trade-offs and usage at different scales.

Model Construction and Research using System Compositional Approach on Natural Hierarchical Neural Networks. Development of Computer Toolbox

System compositional approach to model construction and research of informational processes, which take place in biological hierarchical neural networks, is being discussed. A computer toolbox has been successfully developed for solution of tasks from this scientific sphere. A series of computational experiments investigating the work of this toolbox on olfactory bulb model has been carried out. The well-known psychophysical phenomena have been reproduced in experiments.

Science, research and social change in Indigenous health – evolving ways of knowing

History tells us of the overwhelming destructive influence of exotic culture, politics and knowledge forms upon the worldview and wellbeing of Indigenous Australians. The power of dominant culture to oppress, control and dominate traditional Indigenous ways of knowing and being has been identified as a being a crucial influence on the health status, future hopes and aspirations of Indigenous Australians. Fundamental to this assertion is that the alienating effect of the belief in and application of the scientific method in relation to learning and knowing is a phenomenon that is incompatible with the law and cultural ways of traditional Indigenous people. The establishment of the Centre of Clinical Research Excellence (CCRE) is predicated upon and responds to a deep need in our community today to synthesise the ideological and epistemological premises of an increasing range of cultures and world views. It recognises that clinical research, for example, is important to the health of Aboriginal and Torres Strait Islander peoples, but also that the way such research is designed and carried out is also crucial to its potential to effect change in and improve the state of Indigenous health in Australia. This paper examines knowledge principles and processes associated with research in Indigenous communities, explores emerging research trends in science and proposes an epistemological framework for synthesis of traditional approaches with those of the scientific paradigm.

In search of a social science research methods pedagogy for the digital era: the story so far

Presentation given at the 2016 British Educational Research Association (BERA) conference

Abnormal levels of heterogeneous nuclear ribonucleoprotein A2B1 (hnRNPA2B1) in tumour tissue and blood samples from patients diagnosed with lung cancer

Lung cancer is the second most common type of cancer in the world and is the most common cause of cancer-related death in both men and women. Research into causes, prevention and treatment of lung cancer is ongoing and much progress has been made recently in these areas, however survival rates have not significantly improved. Therefore, it is essential to develop biomarkers for early diagnosis of lung cancer, prediction of metastasis and evaluation of treatment efficiency, as well as using these molecules to provide some understanding about tumour biology and translate highly promising findings in basic science research to clinical application. In this investigation, two-dimensional difference gel electrophoresis and mass spectrometry were initially used to analyse conditioned media from a panel of lung cancer and normal bronchial epithelial cell lines. Significant proteins were identified with heterogeneous nuclear ribonucleoprotein A2B1 (hnRNPA2B1), pyruvate kinase M2 isoform (PKM2), Hsc-70 interacting protein and lactate dehydrogenase A (LDHA) selected for analysis in serum from healthy individuals and lung cancer patients. hnRNPA2B1, PKM2 and LDHA were found to be statistically significant in all comparisons. Tissue analysis and knockdown of hnRNPA2B1 using siRNA subsequently demonstrated both the overexpression and potential role for this molecule in lung tumorigenesis. The data presented highlights a number of in vitro derived candidate biomarkers subsequently verified in patient samples and also provides some insight into their roles in the complex intracellular mechanisms associated with tumour progression.

Cannabinoids and glaucoma - A review

Glaucoma is one of the leading causes of blindness in the world. A wide range of therapeutic possibilities to control the disease and prevent glaucomatous optic nerve damage with subsequent loss of vision already exist. In a relatively high proportion of patients, medical and/or surgical therapies are contraindicated or become non-effective. The purpose of this article is to provide an overview on the latest achievements in the research of potential use of cannabinoids in glaucoma. Methods: The literature on recent basic science research on cannabinoids and a range of research studies using cannabinoids under different preparations and ways of application was reviewed. Conclusions: Cannabinoids effectively lower the intraocular pressure. Newer research findings allow a better understanding of the different possible mechanisms of action of cannabinoids on IOP. Future progress in different research fields concerning possible clinical applications of cannabinoids may offer better preparations with less or possibly no undesired side effects.

Spectrum of Somatic Hypermutations and Implication on Antibody Function: Case of the anti HIV-1 antibody, b12

Thesis (Ph.D.)--University of Washington, 2015

Clinical implications of cognitive bias modification for interpretative biases in social anxiety: an integrative literature review

Cognitive theories of social anxiety indicate that negative cognitive biases play a key role in causing and maintaining social anxiety. On the basis of these cognitive theories, laboratory-based research has shown that individuals with social anxiety exhibit negative interpretation biases of ambiguous social situations. Cognitive Bias Modification for interpretative biases (CBM-I) has emerged from this basic science research to modify negative interpretative biases in social anxiety and reduce emotional vulnerability and social anxiety symptoms. However, it is not yet clear if modifying interpretation biases via CBM will have any enduring effect on social anxiety symptoms or improve social functioning. The aim of this paper is to review the relevant literature on interpretation biases in social anxiety and discuss important implications of CBM-I method for clinical practice and research.

A Test of Absolute Numerousness Judgments in Lion-Tailed Macaques (Macaca Silenus)

Numerous studies have shown that animals have a sense of quantity and can distinguish between relative amounts. The concepts of relative numerousness, estimation, and subitizing are well established in species as diverse as chimpanzees and salamanders. Mobile animals have practical use for an understanding of number in common situations such as predation, mating, and competition. However, the ability to identify discrete quantities has only been firmly established in humans. The purpose of this study was to test for such “absolute numerousness” judgments in three lion-tailed macaques (Macaca silenus), a non-human primate. The three macaques tested had previously been trained on a computerized matchto- sample (MTS) task using geometric shapes. In this study, they were introduced to a MTS task containing a numerical cue, which required the monkeys to match stimuli containing either one or two items for rewards. If monkeys were successful at the initial matching task, they were tested with stimuli in which the position of the items and then the surface area of the items was controlled. If the monkeys could match successfully without using these non-numerical cues, they would demonstrate the capability to make absolute numerousness judgments. None of the monkeys matched successfully using the numerical cue, so no evidence of absolute numerosity was found. Each macaque progressed through the experiment in an individualized manner, attempting a variety of strategies to obtain rewards. These included side preferences and an alternating-side strategy that were unrelated to the numerical cues in the stimuli. When it became clear that the monkeys were not matching based on a stimulus-based cue, they were tested again on matching geometric shapes. All three macaques stopped using their alternate strategies and were able to match shapes successfully, demonstrating that they were still capable of completing the matching task. The data suggest that the monkeys could not transfer this ability to the numerical stimuli. This indicates that the macaques lack a sense of exact quantity, or that they could not recognize the numerical cues in the stimuli as being relevant to the task.

Understanding acquired resistance to Lapatinib in breast cancer cells

Signaling through epidermal growth factor receptor (EGFR/ErbB) family members plays a very important role in regulating proliferation, development, and malignant transformation of mammary epithelial cells. ErbB family members are often over-expressed in human breast carcinomas. Lapatinib is an ErbB1 and ErbB2 tyrosine kinase inhibitor that has been shown to have anti-proliferative effects in breast and lung cancer cells. Cells treated with Lapatinib undergo G1 phase arrest, followed by apoptosis. Lapatinib has been approved for clinical use, though patients have developed resistance to the drug, as seen previously with other EGFR inhibitors. Moreover, the therapeutic efficacy varies significantly within the patient population, and the mechanism of drug sensitivity is not fully understood. Expression levels of ErbB2 are used as a prognostic marker for Lapatinib response; however, even among breast tumor cell lines that express similar levels of ErbB2 there is marked difference in their proliferative responses to Lapatinib. To understand the mechanisms of acquired resistance, we established a cell line SkBr3-R that is resistant to Lapatinib, from a Lapatinib-sensitive breast tumor cell line, SkBr3. We have characterized the cell lines and demonstrated that Lapatinib resistance in our system is not facilitated by receptor-level activity or by previously known mutations in the ErbB receptors. Significant changes were observed in cell proliferation, cell migration, cell cycle and cell death between the Lapatinib resistant SkBr3-R and sensitive SkBr3 cell lines. Recent studies have suggested STAT3 is upregulated in Lapatinib resistant tumors in association with ErbB signaling. We investigated the role that STAT3 may play in Lapatinib resistance and discovered higher STAT3 activity in these resistant cells. In addition, transcriptional profiling indicated higher expression of STAT3 target genes, as well as of other genes that promote survival. The gene array data also revealed cell cycle regulators and cell adhesion/junction component genes as possible mediator of Lapatinib resistance. Altogether, this study has identified several possible mechanisms of Lapatinib resistance.

DOUBLE-STRAND BREAK REPAIR PATHWAYS IN DNA STRUCTURE-INDUCED GENETIC INSTABILITY

Genetic instability in mammalian cells can occur by many different mechanisms. In the absence of exogenous sources of DNA damage, the DNA structure itself has been implicated in genetic instability. When the canonical B-DNA helix is naturally altered to form a non-canonical DNA structure such as a Z-DNA or H-DNA, this can lead to genetic instability in the form of DNA double-strand breaks (DSBs) (1, 2). Our laboratory found that the stability of these non-B DNA structures was different in mammals versus Escherichia coli (E.coli) bacteria (1, 2). One explanation for the difference between these species may be a result of how DSBs are repaired within each species. Non-homologous end-joining (NHEJ) is primed to repair DSBs in mammalian cells, while bacteria that lack NHEJ (such as E.coli), utilize homologous recombination (HR) to repair DSBs. To investigate the role of the error-prone NHEJ repair pathway in DNA structure-induced genetic instability, E.coli cells were modified to express genes to allow for a functional NHEJ system under different HR backgrounds. The Mycobacterium tuberculosis NHEJ sufficient system is composed of Ku and Ligase D (LigD) (3). These inducible NHEJ components were expressed individually and together in E.coli cells, with or without functional HR (RecA/RecB), and the Z-DNA and H-DNA-induced mutations were characterized. The Z-DNA structure gave rise to higher mutation frequencies compared to the controls, regardless of the DSB repair pathway(s) available; however, the type of mutants produced after repair was greatly dictated on the available DSB repair system, indicated by the shift from 2% large-scale deletions in the total mutant population to 24% large-scale deletions when NHEJ was present (4). This suggests that NHEJ has a role in the large deletions induced by Z-DNA-forming sequences. H-DNA structure, however, did not exhibit an increase in mutagenesis in the newly engineered E.coli environment, suggesting the involvement of other factors in regulating H-DNA formation/stability in bacterial cells. Accurate repair by established DNA DSB repair pathways is essential to maintain the stability of eukaryotic and prokaryotic genomes and our results suggest that an error-prone NHEJ pathway was involved in non-B DNA structure-induced mutagenesis in both prokaryotes and eukaryotes.

A METAGENOMIC STUDY OF THE TICK MIDGUT

A Metagenomic Study of the Tick Midgut Daniel Yuan, B.S. Supervisory Professor : Steven J. Norris, Ph.D. Southern tick–associated rash illness (STARI) or Master’s disease is a Lyme-like illness that occurs following bites by Amblyomma americanum, the lone-star tick. Clinical symptoms include a bull’s eye rash similar to the erythema migrans lesions of Lyme disease, as well as fever and joint pains. Lyme disease is caused by Borrelia burgdorferi and related spirochetes. However, B. burgdorferi has not been detected in STARI patients, or in ticks in the South Central U.S. The causative agent of STARI has not been identified, although it was once thought to be caused by another Borrelia species, Borrelia lonestari. Furthermore, while adult A. americanum have up to a 5.6% Borrelia lonestari infection rate, the prevalence of all Borrelia species in Texas ticks as a whole is not known. Previous studies indicate that 6%-30% of Northern Ixodes scapularis ticks are infected by Borrelia burgdorferi while only 10% of Northern A. americanum and I. scapularis ticks are infected by Borrelia species. The first specific aim of this project was to determine the bacterial community that inhabits the midgut of Texas and Northeastern ticks by using high throughput metagenomic sequencing to sequence bacterial 16S rDNA. Through the use of massively parallel 454 sequencing, we were able to individually sequence hundreds of thousands of 16S rDNA regions of the bacterial flora from 133 ticks from the New York, Missouri and Texas. The presence of previously confirmed endosymbionts, specifically the Rickettsia spp. and Coxiella spp., that are commonly found in ticks were confirmed, as well as some highly prevalent genera that were previously undocumented. Furthermore, multiple pathogenic genera sequences were often found in the same tick, suggesting the possibility of co-infection of multiple pathogenic species. The second specific aim was to use Borrelia specific primers to screen 344 individual ticks from Missouri, Texas and the Northeast to determine the prevalence of Borrelia species in ticks. To screen for Borrelia species, two housekeeping genes, uvrA and recG, were selected as well as the 16S-23S rDNA intergenic spacer. Ticks from Missouri, Texas and New York were screened. None of the Missouri or Texas ticks tested positive for Borrelia spp. The rate of I. scapularis infection by B.burgdorferi is dependent on tick feeding activity as well as reservoir availability. B. burgdorferi is endemic in the Northeast, sometimes reported as highly present in over 50% of all I. scapularis ticks. 11.6% of all New York ticks were positive for a species of Borrelia, however only 6.9% of all New York ticks were positive for B. burgdorferi. Despite being significantly lower than 50%, the results still fall in line with previous reports of about the prevalence of B. burgdorferi. 1.5% of all Texas ticks were positive for a Borrelia species, specifically B. lonestari. While this study was unable to identify the causative agent for STARI, 454 sequencing was able to provide a tremendous insight into the bacterial flora and possible pathogenic species of both the I. scapularis and the A. americanum tick.

ELUCIDATING FUNCTIONAL ROLES FOR MYOGENIN IN ADULT SKELETAL MUSCLE METABOLISM, EXERCISE CAPACITY, AND REGENERATION

The four basic helix-loop-helix myogenic transcription factors, myogenin, Myf5, MRF4, and MyoD are critical for embryonic skeletal muscle development. Myogenin is necessary for the terminal differentiation of myoblasts into myofibers during embryogenesis, but little is known about the roles played by myogenin in adult skeletal muscle function and metabolism. Furthermore, while metabolism is a well-studied physiological process, how it is regulated at the transcriptional level remains poorly understood. In this study, my aim was to determine the function of myogenin in adult skeletal muscle metabolism, exercise capacity, and regeneration. To investigate this, I utilized a mouse strain harboring the Myogflox allele and a Cre recombinase transgene, enabling the efficient deletion of myogenin in the adult mouse. Myogflox/flox mice were stressed physically through involuntary treadmill running and by breeding them with a strain harboring the Duchenne’s muscular dystrophy (DMDmdx) allele. Surprisingly, Myog-deleted animals exhibited an enhanced capacity for exercise, running farther and faster than their wild-type counterparts. Increased lactate production and utilization of glucose as a fuel source indicated that Myog-deleted animals exhibited an increased glycolytic flux. Hypoglycemic Myog-deleted mice no longer possessed the ability to outrun their wild-type counterparts, implying the ability of these animals to further deplete their glucose reserves confers their enhanced exercise capacity. Moreover, Myog-deleted mice exhibited an enhanced response to long-term exercise training. The mice developed a greater proportion of type 1 oxidative muscle fibers, and displayed increased levels of succinate dehydrogenase activity, indicative of increased oxidative metabolism. Mdx:Myog-deleted mice exhibited a similar phenotype, outperforming their mdx counterparts, although lagging behind wild-type animals. The morphology of muscle tissue from mdx:Myog-deleted mice appears to mimic that of mdx animals, indicating that myogenin is dispensable for adult skeletal muscle regeneration. Through global gene expression profiling and quantitative (q)RT-PCR, I identified a unique set of putative myogenin-dependent genes involved in regulating metabolic processes. These data suggest myogenin’s functions during adulthood are distinctly different than those during embryogenesis, and myogenin acts as a high-level transcription factor regulating metabolic activity in adult skeletal muscle.