Effects of Apamin and Charybdtoxin on Endothelium Independent Vasodilatation : Implications in the study of EDHF

Endothelial derived hyperpolarizing factor (EDHF), together with endothelial derived NO and prostacyclin represent the major endogenous vasodilator hormone pathways (Coleman et al, 2004). Since the chemical nature of EDHF is uncertain, many studies have relied on pharmacological tools. Often EDHF described as the endothelial dependent dilation which is resistant to a combination of drugs that inhibit NO synthase (usually L-NAME) and cyclo-oxygenase (usually indomethacin) but abolished by those that block large and small Ca2+-activated K+ channels (BKCa and SKCa; with charybdotoxin plus apamin respectively). This approach relies on each of these drugs being selective for endothelial dependent responses. In the current study we have taken a different approach to most and performed experiments where inhibitors were added to endothelium denuded vessels after dilators induced stable vasodilatation. Male Wistar rats (200 ± 15.4g) were killed by lethal exposure to CO2. Second order mesenteric arteries were mounted in isometric wire myographs and vasomotor responses recorded as described previously (Harrington and Mitchell, 2004). In some experiments vessels were contracted with EC80 concentration of U46619, dilation was then induced by the addition of 3x10-6M acetylcholine or 3x10-6M SNP. When either L-NAME (10-4M) or charybdotoxin (10-7M) plus apamin (5x10-7M) were added after acetylcholine the vasodilatation was immediately and completely reversed (Figure A and B respectively). In other experiments, endothelium independent vasodilation induced by SNP, were also reversed by charybdotoxin plus apamin, but not L-NAME. Figure A. Example trace of an artery re-contracting following the addition of L-NAME in pre-contracted arteries dilated with acetylcholine. Bar Graphs show re-contraction of arteries in response to L-NAME or charybdotoxin plus apamin (C+A) in arteries with endothelium, dilated with acetylcholine (Figure B) or without endothelium dilated with SNP (Figure C). This data demonstrates that charybdotoxin and apamin have pharmacological effects independent of the endothelium, at the level of smooth muscle cell function. These observations suggest results obtained with these drugs in relation to EDHF studies, should be treated with caution. Harrington L and Mitchell JA (2004) Br J Pharmacol 143: 611-617 Coleman et al (2004) Clin Ex Pharm Phys 31; 641-649Peer reviewedFinal Accepted Versio

Energy conservation in the one-phase supercooled Stefan problem

© . This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/A one-phase reduction of the one-dimensional two-phase supercooled Stefan problem is developed. The standard reduction, employed by countless authors, does not conserve energy and a recent energy conserving form is valid in the limit of small ratio of solid to liquid conductivity. The present model assumes this ratio to be large and conserves energy for physically realistic parameter values. Results for three one-phase formulations are compared to the two-phase model for parameter values appropriate to supercooled salol (similar values apply to copper and gold) and water. The present model shows excellent agreement with the full two-phase model.Peer ReviewedPostprint (author's final draft

Practical applications of small-angle neutron scattering.

Recent improvements in beam-line accessibility and technology have led to small-angle neutron scattering (SANS) becoming more frequently applied to materials problems. SANS has been used to study the assembly, dispersion, alignment and mixing of nanoscale condensed matter, as well as to characterise the internal structure of organic thin films, porous structures and inclusions within steel. Using time-resolved SANS, growth mechanisms in materials systems and soft matter phase transitions can also be explored. This review is intended for newcomers to SANS as well as experts. Therefore, the basic knowledge required for its use is first summarised. After this introduction, various examples are given of the types of soft and hard matter that have been studied by SANS. The information that can be extracted from the data is highlighted, alongside the methods used to obtain it. In addition to presenting the findings, explanations are provided on how the SANS measurements were optimised, such as the use of contrast variation to highlight specific parts of a structure. Emphasis is placed on the use of complementary techniques to improve data quality (e.g. using other scattering methods) and the accuracy of data analysis (e.g. using microscopy to separately determine shape and size). This is done with a view to providing guidance on how best to design and analyse future SANS measurements on materials not listed below

The ‘EDHF’ Antagonist 14, 15 Epoxyeicosa-5(Z)-Enoic Acid has Vasodilator Properties in Mesenteric Vessels

There is now overwhelming evidence for Epoxyeicosatrienoic acids (EETs) as endothelial derived hyperpolarising factor (EDHF). Most recently, a number of pharmacological tools have been developed for the study of EETs in relation to EDHF responses. EETs have been shown to cause relaxation by activating smooth muscle large conductance Ca2+ sensitive K+ (BKCa) (Archer et al, 2003). This dilatory response has been shown to be specifically inhibited by its analogue 14, 15-epoxyeicosa-5 (Z) enoic acid (14, 15 EEZE) in both human internal mammary artery and bovine coronary artery (Archer et al, 2003). Here we have investigated the antagonist effects of 14, 15 EEZE in murine arteries. Male Black 6 mice (12-18 weeks) were killed by lethal exposure to CO2. First order arteries were isolated and mounted in wire myographs immersed in physiological salt solution (PSS). Arteries were equilibrated (30 mins) and tensions normalised as described previously (Mulvany and Halpern, 1977). Arteries incubated for 30 minutes with or without 3µg/ml 14, 15 EEZE. A concentration response curve to 11, 12 EET was performed cumulatively on arteries pre-contracted with EC80 U46619. In some experiments, arteries were pre-contracted with EC80 U46619, and concentration response to 14, 15 EEZE performed cumulatively.Non peer reviewe

Understanding the Summary Jurisdiction in NSW

This thesis presents an analysis of the NSW summary criminal jurisdiction (the ‘summary jurisdiction’). The summary jurisdiction is a dynamic criminal justice apparatus where magistrates preside over the determination of liability for certain proscribed behaviours in the lower courts without the intervention of a jury. My close analysis of the summary jurisdiction tells the previously little-known story of its development and offers a basis for critique. Adopting a socio-historical approach, this thesis offers a fresh analysis. At a broad level, change over time in the summary jurisdiction can be seen as following a trajectory of formalisation. I argue that ‘formalisation’ is a useful concept for understanding the historical development of the summary jurisdiction. It has four overlapping and interacting dimensions that assume differing degrees of significance at different times. Those dimensions are: juridification; rationalisation; professionalisation together with what I call ‘lawyerification’; and the separation of law from other spheres of social power. Formalisation has been a product of changing legitimation demands and attempts to increase the efficiency of the criminal law. Applying formalisation as a lens through which to view the development of the summary jurisdiction reveals how the summary jurisdiction has achieved the criminalisation of behaviours that have been constructed as harmful

Distribution, Ecology, Disease Risk, and Genetic Diversity of Swift Fox (\u3cem\u3eVulpes Velox\u3c/em\u3e) in the Dakotas

The swift fox (Vulpes velox), a native species once abundant throughout the Northern Great Plains (NGP), has declined due to changes in land use, historic predator eradication programs, and predation by larger canid species. Currently, the species is estimated to occupy 44% of its historic range. In the NGP, the status of the swift fox varies by state, ranging from furbearer to endangered species. However, knowledge of the current status of swift foxes in the NGP is lacking due to an absence of systematic population monitoring. Improving the current state of knowledge concerning swift fox populations in the NGP is necessary to assess the population status of the species and will be instrumental in assisting managers in conservation and, if needed, restoration of this rare species. The swift fox is considered rare in North Dakota and state threatened in South Dakota. We evaluated the distribution of swift fox, red fox (Vulpes vulpes), and coyote (Canis latrans) populations, investigated ecology and life history of swift fox, and assessed disease risk and genetic diversity of resident swift foxes in northwest South Dakota and southwest North Dakota. To accomplish these objectives, we first conducted a systematic camera-trap survey to assess occupancy and distribution of swift fox, coyotes, and red fox. Using camera trap detections and anecdotal sightings, we livetrapped, radio-collared, and tracked swift foxes to locate den sites to assess den site habitat selection. Using samples collected during camera-trap surveys and radio-collaring, we conducted disease and genetic diversity analyses. We conducted occupancy and distribution models at two different scales (sympatric canids: double-home range, 6.68 km, and home range, 3.34 km; swift fox: sub-home range, 30 m, and home range, 3.34 km); both scales created overfit models, producing inaccurate distribution maps for swift fox. Therefore, we do not suggest using either of these models for management purposes. However, we found that coyotes occupied 63-69% of the study area while red fox occupied 46-53% of the study area. We documented average litter sizes (3.25 pups), large home ranges (55.38 km2), late dispersal (February), large dispersal distances (17.20 km), high survival (0.857), and found dens farther from roads than other studies, with no correlation between den-site location and vegetation height. We also found high prevalence of canine parvovirus (71.43%) and Francisella tularensis (67.74%), but low prevalence of canine distemper virus (10.34%) and Yersinis pestis (3.32%). The high prevalence of canine parvovirus and exposure to canine distemper are cause for concern, due to their typically highly fatal outcomes. This swift fox population occupying northwestern South Dakota and southwestern North Dakota is genetically viable, with high intrapopulation connectivity and no sign of a genetic bottleneck. Our study is the first of its kind in northwest South Dakota and southwest North Dakota and most of our findings can and should be used in future monitoring, conservation, and restoration plans for this native species in the Dakotas

The regulation of RNA polymerase III transcription by protein kinase CK2

In order for cells to proliferate, a certain size has to be reached, which depends primarily on the rate of translation. RNA polymerase (pol) III plays a key role in protein synthesis by catalysing the production of small, untranslated RNA molecules such as transfer (tRNA) and 5S ribosomal RNA (5S rRNA). Indeed, recent evidence suggests that tRNAiMet production is limiting for translation and proliferation in some cell types. Therefore, the rate of pol III transcription plays a fundamental role in cellular growth and proliferation. Regulation of pol III output is mediated via a number of different mechanisms that can alter the activities of the transcription factors which are responsible for directing pol III transcription. Work presented in this thesis aimed at investigating the mechanisms behind the regulation of pol III transcription by the protein kinase CK2

Middle School Teachers’ Awareness Of Their Pedagogical Practices Among African American Girls In Their Classrooms

This qualitative narrative research study explores sixth through eighth-grade teachers’ awareness of their practice and pedagogy among African American girls in public suburban middle schools. The guiding research question addressed in this study was: How do teachers describe characteristics associated with their practice and pedagogy of their African American middle school girls? Participants included four suburban middle school teachers selected based on their teaching experiences with African American middle school girls. There were no limitations on participants’ age, race, gender, or if they obtained their teacher certification directly from a college or university or through an alternative certification program. After multiple phases of data refinement, four themes emerged: (a) lack of preparation; (b) instruction and teaching African American girls; (c) impacts on instruction—COVID and society; and (d) relationships and high expectations. The findings from this study indicate that: (a) more targeted preparation is necessary and will be required as pre-service, in-service, and alternative certification teachers work with and instruct African American middle school girls; (b) instructional strategies and lesson delivery that are more appealing, relevant, and engaging are vital; (c) a greater awareness of societal happenings that African American middle school girls are faced with while still being expected to achieve academic success is essential; and (d) a greater understanding of establishing trusting teacher-student relationships while upholding high expectations of African American middle school girls is imperative. If ignored, the topics regarding African American middle school girls, teachers’ lack of preparation to instruct them, and the lack of academic success they have experienced in the classroom will remain. The conversations surrounding these topics will continue as they did over ten years ago, with minimal changes and a lack of significant progress. Keywords: classroom experience, critical consciousness, critical pedagogy, cultural competence, culturally relevant pedagogy, empowerment, middle school, pedagogy, practice, suburba

Emotional Labor and Employee Engagement Within a Pediatric Hospital

High levels of emotional work, staffing shortages, high turnover rates, low workforce engagement levels, and complex healthcare reforms are common problems in healthcare settings. Healthcare leaders are increasingly aware of the vital impact an engaged workforce can have on patient outcomes and an organization\u27s ability to survive despite current challenges in the healthcare setting. It is important for leaders to understand what factors may influence the ability to engage with their organization, such as emotional labor. The purpose of this correlational quantitative study was to test whether emotional labor is related to employee engagement within a large Midwestern pediatric hospital. The theoretical frameworks that helped guide the development of this study were Herzberg\u27s motivation-hygiene theory, Kahn\u27s engagement theory, intergroup emotions theory, and Diefendorff and Richard\u27s model of emotional display rules. Three measures (a demographic questionnaire, the revised Emotional Labour Survey, and the Job Engagement Scale) were used to address the relationship between the variables (the subscales of emotional labor and employee engagement). Data analysis involved simple bivariate correlations and curvilinear regressions. Results indicated that the subscales of faking emotions and hiding feelings negatively correlated with employee engagement. Five of the 6 subscales also had a significant curvilinear relationship with employee engagement. Gender did not play a moderating role in this study. Social change implications and recommendations include the potential for improvements in the need to identify and develop training and self-care strategies necessary for staff to endure the emotional fallout associated with the high emotional demands of their job