Hypothesis testing: how we foresee falsification in competitive games

Each day people are presented with circumstances that may require speculation. Scientists may ponder questions such as why a star is born or how rainbows are made, psychologists may ask social questions such as why people are prejudiced, and military strategists may imagine what the consequences of their actions might be. Speculations may lead to the generation of putative explanations called hypotheses. But it is by checking if hypotheses accurately reflect the encountered facts that lead to sensible behaviour demonstrating a true understanding. If evidence shows a hypothesis to be false, then people should rationally abandon it, especially if there are negative consequences. The aim of this thesis is to examine how effectively people search for evidence in their hypothesis testing to test whether or not their hypotheses are true or false in competitive games. Research findings from six studies of hypothesis testing behaviour in competitive deductive tasks are explored. Chapter by chapter the thesis tests how everyday people, and master chess players, tackle hypothesis testing in mathematical tasks, such as how to solve sequential number sequence puzzles when thinking about an opponent, or how to solve chess problems in a variety of contexts. The implications of the results are discussed in light of aspects of general cognition: such as reasoning, social hypothesis testing and planning

Diagnostic Significance of Exosomal miRNAs in the Plasma of Breast Cancer Patients

Poster Session AbstractsBackground and Aims: Emerging evidence that microRNAs (miRNAs) play an important role in cancer development has opened up new opportunities for cancer diagnosis. Recent studies demonstrated that released exosomes which contain a subset of both cellular mRNA and miRNA could be a useful source of biomarkers for cancer detection. Here, we aim to develop a novel biomarker for breast cancer diagnosis using exosomal miRNAs in plasma. Methods: We have developed a rapid and novel isolation protocol to enrich tumor-associated exosomes from plasma samples by capturing tumor specific surface markers containing exosomes. After enrichment, we performed miRNA profiling on four sample sets; (1) Ep-CAM marker enriched plasma exosomes of breast cancer patients; (2) breast tumors of the same patients; (3) adjacent non-cancerous tissues of the same patients; (4) Ep-CAM marker enriched plasma exosomes of normal control subjects. Profiling is performed using PCR-based array with human microRNA panels that contain more than 700 miRNAs. Results: Our profiling data showed that 15 miRNAs are concordantly up-regulated and 13 miRNAs are concordantly down-regulated in both plasma exosomes and corresponding tumors. These account for 25% (up-regulation) and 15% (down-regulation) of all miRNAs detectable in plasma exosomes. Our findings demonstrate that miRNA profile in EpCAM-enriched plasma exosomes from breast cancer patients exhibit certain similar pattern to that in the corresponding tumors. Based on our profiling results, plasma signatures that differentiated breast cancer from control are generated and some of the well-known breast cancer related miRNAs such as miR-10b, miR-21, miR-155 and miR-145 are included in our panel list. The putative miRNA biomarkers are validated on plasma samples from an independent cohort from more than 100 cancer patients. Further validation of the selected markers is likely to offer an accurate, noninvasive and specific diagnostic assay for breast cancer. Conclusions: These results suggest that exosomal miRNAs in plasma may be a novel biomarker for breast cancer diagnosis.link_to_OA_fulltex

Structural studies of the human glyoxylate reductase/hydroxypyruvate reductase (GRHPR) and other proteins

Human glyoxylate reductase/hydroxypyruvate reductase (GRHPR) is a D-2-hydroxyacid dehydrogenase found predominantly within the liver, and is essential for the removal of the reactive metabolic product glyoxylate. Primary hyperoxaluria type 2 (PH2) disease, which is characterised by increased urinary oxalate and L-glycerate levels leading to calcium oxalate deposition and decreased renal function, is caused by mutations in the gene for GRHPR. In this study the first crystal structures of the human GRHPR enzyme are reported. Structures of apo, binary and ternary forms of GRHPR are reported, the latter being the first structure of a true ternary complex of an enzyme from the D-2-hydroxyacid dehydrogenase family.EThOS - Electronic Theses Online ServiceGBUnited Kingdo