Mathematical Zendo: A game of patterns and logic

Mathematical Zendo is a logic game that actively engages participants in pattern recognition, problem solving, and critical thinking while providing a fun opportunity to explore all manner of mathematical objects. Based upon the popular game of Zendo, created by Looney Labs, Mathematical Zendo centers on a secret rule, chosen by the leader, that must be guessed by teams of players. In each round of the game, teams provide examples of the mathematical object of interest (e.g. functions, numbers, sets) and receive information about whether their guesses do or do not satisfy the secret rule. In this paper, we introduce Mathematical Zendo, provide examples of games and rules that have proven to be engaging over testing with hundreds of students and teachers, and discuss best practices for implementation

Location-allocation Model Effectiveness in Public Facilities Location

This thesis investigates the influence of study area scale on computer location-allocation model effectiveness in the public sector problem. The ideas for this study developed from my work on projects for the Stillwater School System and Putnam City Schools.Geograph

Evaluations of Livestock Protection Dogs for Deterring Deer and Cattle Interactions

Bovine Tuberculosis (bovine TB) in northern Michigan has proven a dilemma necessitating aggressive measures including depopulation of livestock operations, culling of wildlife, banning the feeding of wildlife, and fencing livestock feed with high fences. Bovine TB is believed to be transmitted from white-tailed deer (Odocoileus virginianus) to domestic cattle through feces, urine, saliva, and nasal secretions on contaminated feed (indirect transmission) and from animal to animal (direct transmission). Effective methods for excluding deer from cattle enclosures would minimize the potential for indirect and direct transmission of bovine TB between infected deer and cattle. We combined an idea used historically in Europe to control predation on sheep with the concept of modem frightening devices that often fall short when the motivation of offending species is high. The use of livestock protection dogs (LPDs) seemed like an ideal solution in controlling the transmission of bovine TB from white-tailed deer to cattle. We felt LPDs raised and bonded with cattle would reduce use of cattle pastures and cattle feed by deer and minimize contact between deer and cattle, thereby reducing the potential for the transmission of bovine TB. We evaluated 4 LPDs over a 5-month period utilizing 2 primary data collection methods (direct observations and motion-activated video) on farmed deer facilities in Michigan. Following the initial evaluation of the LPDs, we relocated the dogs to working livestock operations in Michigan for further evaluation to gain an understanding of their practicality and long-term efficacy. Pastures protected by dogs had fewer intrusions by deer, fewer contacts (within 5m) between deer and cattle, and lower use of cattle feed by deer. Overall, we successfully decreased the potential for disease transmission with 66% fewer intrusions by deer into protected pastures, 96% fewer contacts (within 5m) between deer and cattle, and 100% lower use of cattle feed by deer (based of observation data). Livestock protection dogs were more effective in protecting animals and their immediate surroundings than excluding animals from entire study pastures. We found a strong treatment effect within the High Density Site; while within the Very High Density Site, we had high variability within intrusion rates at protected pastures and relatively low use of unprotected pastures resulting in no significant treatment effect. In conclusion, when properly trained and confined with the protected animals, LPDs minimize the potential for livestock to contract bovine TB from infected deer

Reduced number of axonal mitochondria and tau hypophosphorylation in mouse P301L tau knockin neurons.

Expression of the frontotemporal dementia-related tau mutation, P301L, at physiological levels in adult mouse brain (KI-P301L mice) results in overt hypophosphorylation of tau and age-dependent alterations in axonal mitochondrial transport in peripheral nerves. To determine the effects of P301L tau expression in the central nervous system, we examined the kinetics of mitochondrial axonal transport and tau phosphorylation in primary cortical neurons from P301L knock-in (KI-P301L) mice. We observed a significant 50% reduction in the number of mitochondria in the axons of cortical neurons cultured from KI-P301L mice compared to wild-type neurons. Expression of murine P301L tau did not change the speed, direction of travel or likelihood of movement of mitochondria. Notably, the angle that defines the orientation of the mitochondria in the axon, and the volume of individual moving mitochondria, were significantly increased in neurons expressing P301L tau. We found that murine tau phosphorylation in KI-P301L mouse neurons was diminished and the ability of P301L tau to bind to microtubules was also reduced compared to tau in wild-type neurons. The P301L mutation did not influence the ability of murine tau to associate with membranes in cortical neurons or in adult mouse brain. We conclude that P301L tau is associated with mitochondrial changes and causes an early reduction in murine tau phosphorylation in neurons coupled with impaired microtubule binding of tau. These results support the association of mutant tau with detrimental effects on mitochondria and will be of significance for the pathogenesis of tauopathies

Mislocalization of neuronal tau in the absence of tangle pathology in phosphomutant tau knockin mice.

Hyperphosphorylation and fibrillar aggregation of the microtubule-associated protein tau are key features of Alzheimer's disease and other tauopathies. To investigate the involvement of tau phosphorylation in the pathological process, we generated a pair of complementary phosphomutant tau knockin mouse lines. One exclusively expresses phosphomimetic tau with 18 glutamate substitutions at serine and/or threonine residues in the proline-rich and first microtubule-binding domains to model hyperphosphorylation, whereas its phosphodefective counterpart has matched alanine substitutions. Consistent with expected effects of genuine phosphorylation, association of the phosphomimetic tau with microtubules and neuronal membranes is severely disrupted in vivo, whereas the phosphodefective mutations have more limited or no effect. Surprisingly, however, age-related mislocalization of tau is evident in both lines, although redistribution appears more widespread and more pronounced in the phosphomimetic tau knockin. Despite these changes, we found no biochemical or immunohistological evidence of pathological tau aggregation in mice of either line up to at least 2 years of age. These findings raise important questions about the role of tau phosphorylation in driving pathology in human tauopathies

How patient participation was used to develop a questionnaire that is fit for purpose for assessing quality of life in severe asthma.

BACKGROUND: Previous research shows that existing asthma quality of life questionnaires fail to measure the burden of oral corticosteroids that can be used to treat severe asthma, and are therefore not fit for purpose for severe asthma according to the USA's Federal Drug Authority's (FDA) criteria for content validity. Patient input and documentation of that input is key to achieving content validity according to FDA guidelines. This paper describes the process of constructing a new questionnaire to measure the burden of asthma symptoms and burden of treatment in severe asthma, using criteria specified by the FDA. METHODS: A draft severe asthma questionnaire (SAQ) was constructed using qualitative input from severe asthma patients who took part in an earlier study. The aim of this study was to improve that draft questionnaire using a further group of patients. In four iterative focus groups, 16 people with severe asthma completed the draft questionnaire, discussed the wording and structure and suggested changes that were incorporated into the final version. RESULTS: The original intention to ask patients to identify whether problems were caused by asthma symptoms or side effects of medication was abandoned as the attribution of cause was found to be difficult and inconsistent. The recall period of 2 weeks was acceptable but fails to reflect the patients' desire to express the variability of severe asthma. Patients suggested improvements to the wording of the draft questionnaire, including splitting some items in two, combining two items in one, and changes to some of the words in individual items and the response scale. CONCLUSIONS: The final version of the questionnaire was substantially different from one constructed using only qualitative reports from patients about the quality of life deficits of severe asthma. Patients make a valuable contribution to the questionnaire if they are asked to comment and improve an initial draft and where patients are treated as partners in the process of questionnaire construction, rather than only as a source of information to experts who construct the questionnaire

Characterizing Genetic Risk at Known Prostate Cancer Susceptibility Loci in African Americans

GWAS of prostate cancer have been remarkably successful in revealing common genetic variants and novel biological pathways that are linked with its etiology. A more complete understanding of inherited susceptibility to prostate cancer in the general population will come from continuing such discovery efforts and from testing known risk alleles in diverse racial and ethnic groups. In this large study of prostate cancer in African American men (3,425 prostate cancer cases and 3,290 controls), we tested 49 risk variants located in 28 genomic regions identified through GWAS in men of European and Asian descent, and we replicated associations (at p≤0.05) with roughly half of these markers. Through fine-mapping, we identified nearby markers in many regions that better define associations in African Americans. At 8q24, we found 9 variants (p≤6×10−4) that best capture risk of prostate cancer in African Americans, many of which are more common in men of African than European descent. The markers found to be associated with risk at each locus improved risk modeling in African Americans (per allele OR = 1.17) over the alleles reported in the original GWAS (OR = 1.08). In summary, in this detailed analysis of the prostate cancer risk loci reported from GWAS, we have validated and improved upon markers of risk in some regions that better define the association with prostate cancer in African Americans. Our findings with variants at 8q24 also reinforce the importance of this region as a major risk locus for prostate cancer in men of African ancestry