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Item Biophysical studies of cholesterol in unsaturated phospholipid model membranes(2013) Williams, Justin A.; Wassall, Stephen R.; Decca, Ricardo; Petrache, Horia; Zhu, Fangqiang; Todd, Brian A.Cellular membranes contain a staggering diversity of lipids. The lipids are heterogeneously distr ibuted to create regions, or domains, whose physical properties differ from the bulk membrane and play an essential role in modulating the function of resident proteins. Many basic questions pertaining to the formation of these lateral assemblies remain. T his research employs model membranes of well - defined composition to focus on the potential role of polyunsaturated fatty acids (PUFAs) and their interaction with cholesterol (chol) in restructuring the membrane environment. Omega - 3 (n - 3) PUFAs are the main bioactive components of fish oil, whose consumption alleviates a variety of health problems by a molecular mechanism that is unclear. We hypothesize that the incorporation of PUFAs into membrane lipids and the effect they have on molecular organization may be, in part, responsible. Chol is a major constituent in the plasma membrane of mammals. It determines the arrangement and collective properties of neighboring lipids, driving the formation of domains via differential affinity for different lipids . T he m olecular organization of 1 -[ 2 H 31 ]palmitoyl -2- eicosapentaenoylphosphatidylcholine (PEPC - d 31 ) and 1 -[ 2 H 31 ]palmitoyl -2- docosahexaenoylphosphatidylcholine (PDPC -d 31 ) in membran es with sphingomyelin (SM) and chol (1:1:1 mol) was compared by solid - state 2 H NMR spectroscopy. Eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids are the two major n - 3 PUFAs found in fish oil, while PEPC -d 31 and PDPC -d 31 are phospholipids containing the respective PUFAs at the sn - 2 position and a perdeuterated palmitic acid a t the sn - 1 position . Analysis of s pectra recorded as a function of temperature indicate s that in both cases, formation of PUFA - rich (less ordered) and SM - rich (more ordered) domains occurred. A surprisingly substantial proportion of PUFA was found to infil trate the more ordered domain. There was almost twice as much DHA (65%) as EPA (30%) . The implication is that n - 3 PUFA s can incorporate into lipid rafts, which are domains enriched in SM and chol in the plasma membrane, and potentially disrupt the activity of signaling proteins that reside therein. DHA, furthermore, may be the more potent component of fish oil. PUFA - chol interactions were also examined through affinity measurements. A novel method utilizing electron paramagnetic resonance (EPR) was develope d, to monitor the partitioning of a spin - labeled analog of chol , 3β - doxyl - 5α - cholestane (chlstn), between large unilamellar vesicles (LUVs) and met hyl - β - cyclodextrin (mβCD). The EPR spectra for chlstn in the two environments are distinguishable due to the substantial differences in tumbling rates , allowing the population distribution ratio to be determined by spectral simulation. Advantages of this approach include speed of implementation and a vo idance of potential artifact s associated with physical separation of LUV and mβCD . Additionally, in a check of the method, t he relative partition coefficients between lipids measured for the spin label analog agree with values obtained for chol by isothermal titration calorimetry (ITC). Results from LUV with different composition confirmed a hierarchy of decreased sterol affinity for phospholipids with increasing acyl chain unsaturation , PDPC possessing half the affinity of the corresponding monounsaturated phospholipid. Taken together, the results of these studies on model membranes demonstrate the potential for PUFA - driven alteration of the architecture of biomembranes, a mechanism through which human health may be impacted.Item Creation and validation of tool to assess resident competence in neonatal resuscitation(Elsevier, 2018) Kane, Sara K.; Lorant, Diane E.; Pediatrics, School of MedicineBackground The American Board of Pediatrics requires that pediatricians be able to initiate stabilization of a newborn. After residency, 45% of general pediatricians routinely attend deliveries. However, there is no standard approach or tool to measure resident proficiency in newborn resuscitation across training programs. In a national survey, we found a large variability in faculty assessment of the amount of supervision trainees need for various resuscitation scenarios. Objective documentation of trainee performance would permit competency-based decisions on the level of supervision required and facilitate feedback on trainee performance. Methods A simplified tool was created following the Neonatal Resuscitation Program (NRP) algorithm, with emphasis on communication, leadership, knowledge of equipment, and initial stabilization. To achieve content validity, the tool was evaluated by the NRP steering committee. To assess internal structure of the tool, we filmed 10 simulated resuscitation scenarios 9 of which contained errors. Experienced resuscitation team members used the tool to assess performance of the team leader in the videos. To evaluate the response process, the tool was used to assess experienced resuscitators in real time at academic and non-academic sites. Results The NRP steering committee approved the tool, providing evidence of content validity. Performance of the team leader in the simulated videos was assessed by 16 evaluators using the tool. There was an intra-class coefficient of 0.86 showing excellent agreement. There was no statistical difference in scores between 102 resuscitations led by experienced resuscitators at academic and non-academic hospitals (p=0.98), which demonstrates generalizability. Conclusions The tool we have developed to assess performance in initiating newborn resuscitation shows evidence of construct validity based on assessment of content and internal structure (inter-observer agreement, response processes, and generalizability).Item Representative Bureaucracy, Distributional Equity, and Environmental Justice(Wiley, 2020) Liang, Jiaqi; Park, Sanghee; Zhao, TianshuThis article explores the role of bureaucratic representation and distributional equity in the implementation of environmental policy, which has been shaped by the politics of identity, administrative discretion, and a contested discourse on the redistribution of public resources. We examine whether minority bureaucratic representation fosters policy outputs for race-related disadvantaged communities, and whether the behavior of public administrators reflects distributional equity. Linking representative bureaucracy to environmental justice, this research contributes to the understanding of social equity in public administration and sheds light on the relationship between bureaucratic representation and democratic values. Analyzing a nationwide, block-group-level dataset, we find that a more racially representative workforce in the U.S. Environmental Protection Agency promotes the agency’s enforcement actions in communities that have large local-national disparity in minority population and severe policy problem. But the size of bureaucratic representation effect is larger for neighborhoods that are overburdened with race-related social vulnerability.