Preferences for Government Size and their Effect on Labor-Leisure Decisions

While many economists have theorized and/or empirically demonstrated that labor-leisure decisions are influenced by the rate of taxation, this note introduces a new mechanism in which the collecting of taxes on income may affect such decisions. Although standard models assume that agents have no preference for the size and scope of government activity, recent and past political rhetoric suggests that preferences do exist. We examine how labor-leisure decisions can be affected when taxes are derived from income and agents' utility functions include a preference for government size.

“How Do I Shrink Myself?” A Veteran Assistant Principal’s Micropolitical Experiences in an Unfamiliar Rural School

The purpose of this study was to explore the micropolitical actions of a new-to-place veteran assistant principal in an unfamiliar rural site. Past research offers several different perspectives about the experiences of assistant principals, including socialization and job duties. There is little research, however, on veteran assistant principals who enter new assignments, or on assistant principals working in rural communities. Using an exemplary case design using the theory of micropolitics, I examined an assistant principal’s ability to perform the expectations of the job while addressing challenges resulting from local site characteristics. Through data triangulation of semi-structured interviews, observations, and document analysis, the themes of community expectations, communication, and the effects of conflict were identified. The assistant principal excelled in using social media and honoring local expectations as micropolitical acts. However, the assistant principal struggled in responding to conflict. The findings revealed how micropolitics can be mutually beneficial in rural schools when school leaders align their communication practices with those of the community. The findings also explain the importance of rural APs understanding the expectations of community members and choosing appropriate micropolitical responses. The results indicated that assistant principals must honor and understand rural community characteristics while acknowledging that conflict is an inherent aspect of micropolitical actions in schools. The significance of my study is that it is one of the first to address veteran assistant principals in rural settings. For scholarship and research, this study provides a foundation for future scholarship on the micropolitical actions of assistant principals in rural communities. For practitioners, the study suggests the need for assistant principals to identify ways in which they can improve a school community while increasing their own political standing. For educational leaders, the results indicate a need to increase mentoring for assistant principals with a particular emphasis on managing conflict

FINAL REPORT FOR INDEPENDENT CONFIRMATORY SURVEY SUMMARY AND RESULTS FOR THE HEMATITE DECOMMISSIONING PROJECT, FESTUS, MISSOURI

ORAU conducted confirmatory surveys of the Hematite site during the period of June 12 through June 13, 2012. The survey activities included in-process inspections, document review, walkover surveys, sampling activities, and laboratory analysis of split samples. WEC was forthcoming with information relating to practices, procedures, and surface scan results. Scans performed by the WEC technician were extremely thorough and methodical. The WEC and ORAU technicians identified the same areas of elevated activity with comparable detector responses. WEC sampling of re-use soils, waste soils, sediments, and groundwater were conducted under ORAU observation. The sampling efforts observed by ORAU were performed in accordance with site-specific procedures and in a manner sufficient to provide quality supporting data. Three observations were made during groundwater sampling activities. First, the water level indicator was re-used without submitting rinse blank. Second, bubbles created during tubing extraction could indicate the presence of volatilized organic compounds. Third, samplers did not use a photo ionization detector prior to sample collection to indicate the presence of volatile organic vapors. Results of split samples indicated a high level of comparability between the WEC and ORAU/ORISE radiological laboratories. Analytical practices and procedures appear to be sufficient in providing quality radiochemical data. All concentrations from the Soil Re-Use Area and sediment samples are below Uniform radionuclide-specific derived concentration guideline level (DCGL{sub W}) limits; thus, comparisons to the less conservative stratified geometry were not required. Results were compared to individual DCGLs and using the sum of fractions approach. Both composite soil samples collected from the Waste Handling Area (Bins 1 and 4) were well below the prescribed USEI waste acceptance criteria

Melatonin Alters Age-Related Changes in Transcription Factors and Kinase Activation

Male mice were fed 40 ppm melatonin for 2 months prior to sacrifice at age 26 months, and compared with both 26 and 4 month-old untreated controls. The nuclear translocation of NF-κB increased with age in both brain and spleen and this was reversed by melatonin only in brain. Another transcription factor, AP-1 was increased with age in the spleen and not in brain and this could be blocked by melatonin treatment. The fraction of the active relative to the inactive form of several enabling kinases was compared. The proportion of activated ERK was elevated with age in brain and spleen but this change was unresponsive to melatonin. A similar age-related increase in glial fibrillary acidic protein (GFAP) was also refractory to melatonin treatment. The cerebral melatonin M1 receptor decreased with age in brain but increased in spleen. The potentially beneficial nature of melatonin for the preservation of brain function with aging was suggested by the finding that an age-related decline in cortical synaptophysin levels was prevented by dietary melatonin

BACE1 Gene Regulation: A Novel Drug Target in Alzheimer’s Disease

poster abstractAlzheimer’s disease (AD) is the most common form of dementia in the elderly in the United States. AD is characterized by the presence of amyloid-β (Aβ) peptide plaques. Aberrant deposition is believed to result from the misregulation of the production or the clearance of Aβ. The rate-limiting step in Aβ production is the processing of amyloid- β precursor protein (APP) by β-site APP-cleaving enzyme (BACE1). BACE1 could play a critical role in the development of AD and is a promising drug target. In this study, we aim to reduce BACE1 enzyme levels by reducing BACE1 gene expression. We previously analyzed the promoter activity of BACE1 and the 5’ untranslated region of BACE1 mRNA. The BACE1 promoter contains many transcription factor sites including SP1, MEF2, and STAT1, which have been shown to play a role in the regulation of BACE1 gene expression. Mithramycin A (MithA) has been previously shown to selectively inhibit SP1-mediated transcriptional activation. We expect inhibition of SP1 to lead to downregulation of BACE1 and decreased Aβ, providing a novel target for AD. We have tested several BACE1 promoter-deletion constructs by DNA transfection in human neuronal cultures, treatment with MithA, and performed luciferase reporter assays. In a neuroblastoma (NB) cell line, we observed the significant increase in luciferase reporter activity of two BACE1 plasmid constructs after treatment with MithA. Treatment also correlated with an increase in BACE1 protein expression and a decrease in APP expression. This suggests that the mechanism by which MithA influences the BACE1 promoter could be complex and or due to other transcription factor sites as well. Further experiments will include using differentiated NB cells and human primary fetal neurons, along with the use of other Sp1 inhibitors including tolfenamic acid to elucidate the regulation of APP and BACE1 promoters leading to lower Aβ levels

EVALUATION OF GENE REGULATION AND THERAPEUTIC DRUGS RELATED TO ALZHEIMER’S DISEASE IN DEGENERATING PRIMARY CEREBROCORTICAL CULTURES

Indiana University-Purdue University Indianapolis (IUPUI)Alzheimer’s disease (AD) is a neurological disorder defined by the presence of plaques comprised mostly of amyloid-β (Aβ), and neurofibrillary tangles consisting of hyperphosphorylated microtubule associated protein tau (MAPT). AD is also characterized by widespread synapse loss and degeneration followed by death of neurons in the brain. Inflammatory processes, such as glial activation, are also implicated. In order to study mechanisms of neurodegeneration and evaluate potential therapeutic agents that could slow or reverse this process, a tissue culture system was developed based on primary embryonic cerebrocortical neurons. This culture system was observed to exhibit time-dependent neurodegeneration, glial proliferation, and synaptic marker loss consistent with AD-affected brains. The regulatory promoter regions of several genes implicated in AD, including the Aβ precursor protein (APP), β-amyloid cleaving enzyme (BACE1), and MAPT, were studied in this culture model. The MAPT gene promoter activity followed the pattern of neuronal maturation and degeneration quite closely, increasing in the initial phase of the tissue culture, then reducing markedly during neurodegeneration while APP and BACE1 gene promoters remained active. Deletion series of these promoters were tested to give an initial indication of the active regions of the gene promoter regions. Furthermore, the effects of exogenous Aβ and overexpression of p25, which are two possible pathogenic mechanisms of gene regulation in AD, were studied. Response to Aβ varied between the promoters and by length of the Aβ fragment used. Overexpression of p25 increased MAPT, but not APP or BACE1, promoter activity. This neurodegeneration model was also used to study the putative neuroprotective action of the NMDA receptor antagonist memantine. Treatment with memantine prevented loss of synaptic markers and preserved neuronal morphology, while having no apparent effect on glial activation. The protective action on synaptic markers was also observed with two other structurally distinct NMDA receptor antagonists, suggesting that the effects of memantine are produced by its action on the NMDA receptor. It is concluded that this tissue culture model will be useful for the study of gene regulation and therapeutic agents for neurodegeneration, and that the efficacy of memantine may result from preservation of synaptic connections in the brain

Changing the narrative on COVID-19: Shifting mindsets and teaching practices in higher education

In light of the COVID-19 pandemic, universities around the world urgently suspended face-to-face classes halted practicum field experiences, mandated temporary closures of campuses, and directed faculty to convert face-to-face courses to a hybrid format, all with very little time to prepare. This crisis created unsettled feelings. Varied perceptions along with a narrative of uncertainty, panic, fear, doubt, and dread emerged. Faculty were expected to provide effective learning opportunities and continuous learning experiences with little to no disruption. However, the processes involved in making this happen are elusive and complex. Five faculty from a higher education institution in the United Arab Emirates explored challenges and mechanisms, especially through the process of reflective vignettes. In order to collect and analyze data, collaborative autoethnography was employed as it is a fitting and timely research design and methodology. Collaborative autoethnography is a self-reflection alternative research approach that researchers use during global pandemics. Each vignette offers a first-hand account and experience. The five vignettes highlight tangible solutions and offer salient recommendations that may make the end result of this process smoother and the outcomes more favorable for both faculty and students. Ultimately, the faculty implemented a mindset for the moment and reflexively transformed how they engaged in teaching and learning. Consequently, the faculty moved past negative rhetoric and perception of fear, panic, and chaos, and as such, they changed the narrative on COVID-19

Sleep characteristics modify the association between genetic predisposition to obesity and anthropometric measurements in 119,679 UK Biobank participants

Background - Obesity is a multifactorial condition influenced by genetics, lifestyle and environment. Objective - To investigate whether the association between a validated genetic profile risk score for obesity (GPRS-obesity) with body mass index (BMI) and waist circumference (WC) was modified by sleep characteristics. Design - This study included cross-sectional data from 119,859 white European adults, aged 37-73 years, participating on the UK Biobank. Interactions between GPRS-obesity, and sleep characteristics (sleep duration, chronotype, day napping, and shift work) in their effects on BMI and WC were investigated. Results - The GPRS-obesity was associated with BMI (β:0.57 kg.m-2 per standard deviation (SD) increase in GPRS, [95%CI:0.55, 0.60]; P=6.3x10-207) and WC (β:1.21 cm, [1.15, 1.28]; P=4.2x10-289). There were significant interactions between GPRS-obesity and a variety of sleep characteristics in their relationship with BMI (P-interaction <0.05). In participants who slept <7 hrs or >9 hrs daily, the effect of GPRS-obesity on BMI was stronger (β:0.60 [0.54, 0.65] and 0.73 [0.49, 0.97] kg.m-2 per SD increase in GPRS, respectively) than in normal length sleepers (7-9 hours; β:0.52 [0.49, 0.55] kg.m-2 per SD). A similar pattern was observed for shiftworkers (β:0.68 [0.59, 0.77] versus 0.54 [0.51, 0.58] kg.m-2 for non-shiftworkers) and for night-shiftworkers (β:0.69 [0.56, 0.82] versus 0.55 [0.51, 0.58] kg.m-2 for non-night- shiftworkers), for those taking naps during the day (β:0.65 [0.52, 0.78] versus 0.51 [0.48, 0.55] kg.m-2 for those who never/rarely had naps) and for those with a self-reported evening chronotype (β:0.72 [0.61, 0.82] versus β:0.52 [0.47, 0.57] kg.m-2 for morning chronotype). Similar findings were obtained using WC as the outcome. Conclusions – This study shows that the association between genetic risk for obesity and phenotypic adiposity measures is exacerbated by adverse sleeping characteristics

Risk estimation using probability machines

BACKGROUND: Logistic regression has been the de facto, and often the only, model used in the description and analysis of relationships between a binary outcome and observed features. It is widely used to obtain the conditional probabilities of the outcome given predictors, as well as predictor effect size estimates using conditional odds ratios. RESULTS: We show how statistical learning machines for binary outcomes, provably consistent for the nonparametric regression problem, can be used to provide both consistent conditional probability estimation and conditional effect size estimates. Effect size estimates from learning machines leverage our understanding of counterfactual arguments central to the interpretation of such estimates. We show that, if the data generating model is logistic, we can recover accurate probability predictions and effect size estimates with nearly the same efficiency as a correct logistic model, both for main effects and interactions. We also propose a method using learning machines to scan for possible interaction effects quickly and efficiently. Simulations using random forest probability machines are presented. CONCLUSIONS: The models we propose make no assumptions about the data structure, and capture the patterns in the data by just specifying the predictors involved and not any particular model structure. So they do not run the same risks of model mis-specification and the resultant estimation biases as a logistic model. This methodology, which we call a “risk machine”, will share properties from the statistical machine that it is derived from