2,600 research outputs found

    PRINCIPALS’ PERCEPTIONS OF ENABLING AND HINDERING BEHAVIORS, RULES, AND STRUCTURES IN NEW YORK STATE SCHOOL DISTRICTS

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    There has been increasing recognition among researchers and practitioners that the demands of the principalship have become unsustainable. School districts play a pivotal role in supporting school leaders in the execution of their responsibilities. The purpose of this mixed methods study was to further uncover how school district bureaucracies enable and hinder the work of principals. In the quantitative phase of the study the researcher analyzed survey responses from 244 New York State principals to determine the extent to which district structures were perceived as hindering or enabling their work. In the qualitative phase, the researcher interviewed two principals, one who described their district as enabling and one who described their district as hindering. The researcher analyzed interview transcripts using two cycles of coding to first identify hindering and enabling structures of the district bureaucracy, and then examine how the identified behaviors, rules, and structures hindered or enabled the work of school leaders. The perceptions by principals of enabling and hindering behaviors, rules, and structures were the basis for creating prototypes of enabling and hindering district practices

    Bioregenerative Dietary Supplementation: Optimizing Brassica Production for Space Travel Through Light Intensity, Photoperiod, and Harvest Methodology

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    Bioregenerative dietary supplementation, a component of bioregenerative life support, will be necessary for the success of future exploration-length space endeavors. Plants, as autotrophic producers of calories, nutrients, and oxygen, will be indispensable in the development of these systems. Previous work has identified leafy greens from the genus Brassica as promising candidates for in-flight production of necessary human nutrients such as vitamins C, B1, and K1, in addition to β-carotene, the primary vitamin A precursor in the human diet. These plants also produce lutein and zeaxanthin, two compounds important in protecting the eye from radiation-induced damage, as well as a variety of anthocyanins which act as general antioxidants in the human body, potentially decreasing the damaging effect of free-radicals. Finally, plants accumulate minerals in their tissue, including calcium, potassium, magnesium, and iron; all of which have important implications in the diet of space-faring humans. This thesis seeks to determine 1) which cultivars of Brassica (selected from three species within the genus) produce the most promising phytonutrient and morphological profiles for production in space, 2) how light intensity and photoperiod can be manipulated to increase these phytonutrient concentrations, and 3) how a continuous or ‘cut-and-come-again’ harvest strategy can be implemented to maximize phytonutrient yield efficiency. This was tested by growing plants in a controlled environment growth chamber emulating the temperature, humidity, and CO2 concentration aboard the International Space Station (ISS), and performing a series of phytonutrient extractions and quantifications on the resulting tissue. Of the cultivars evaluated, B. carinata ‘Amara’ provides the strongest phytonutrient profile, an aspect of which was the notable production of higher vitamin B1 concentrations than any cultivar of B. rapa var. nipposinica. A high light intensity, 800 µmol⋅m-2⋅s-1, applied across a 16-hr photoperiod further optimized the profiles of this cultivar and of a complementary cultivar, B. rapa var. nipposinica ‘Red Hybrid’, for space production. Finally, a continuous harvest protocol increased the phytonutrient production per day per unit of production space when compared to a single harvest approach, and these gains increased over subsequent harvests

    Mechanisms of g-protein coupled receptor-dependent opening of transient receptor potential vanilloid-4

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    Transient receptor potential vanilloid-4 (TRPV4) is a non-selective cation channel, involved in thermosensation, mechanosensation and osmosensation. Emerging evidence has identified that the TRPV4 channel is opened by signalling from G-protein coupled receptors (GPCR). TRPV4 is widely expressed; we focused on responses identified in pain sensing neurons, kidney tubule epithelium and the vascular endothelium. The channel has been linked to several pathophysiologies, such as mechanical hyperalgesia and peripheral oedema. TRPV4 integrates a wide range of stimuli which suggests that direct pharmacological modulation of TRPV4 may be difficult. We aimed to determine the signalling from GPCRs that open TRPV4 channels, as these signalling pathways have not been identified and may prove better targets for pharmacological intervention in TRPV4 related pathophysiologies than modulation of TRPV4. To assess these the ability of GPCRs to open TRPV4 channels in human embryonic kidney cells (HEK) were used as they endogenously expressed the pro-inflammatory GPCR protease activated receptor-2 (PAR2) and can be stably transfected with hTRPV4 (HEK+TRPV4) using the T-REx inducible system. It was shown that stimulation of PAR2 with its peptide agonist PAR2-activating peptide (PAR2-AP) released intracellular calcium from stores in HEK cells and opened the TRPV4 channel in HEK+TRPV4 cells. It was demonstrated that blockade of the G-alpha q pathway inhibited the release of intracellular calcium from stores in both HEK and HEK+TRPV4 but did not inhibit the PAR2-dependent opening of TRPV4 in HEK+TRPV4 cells. This indicated that PAR2-dependent opening of TRPV4 does not require release of calcium from intracellular or G-alpha q signalling. Therefore to discover the signalling pathways involved in the PAR2-dependent opening of TRPV4 we developed and optimised a screening process using short interfering ribonucleic acids (siRNAs) to block protein expression  firstly of protein kinases, as the PAR2-dependent opening of TRVP4 has evidence that it is kinase dependent and secondly, of G-proteins and their associated signalling molecules. The screen of the kinome (the expression of the current known kinases in the human genome) identified with high confidence four siRNAs, siBUB1, siITPK1, siMAPK13 and siITPK1 that were able to interfere with the PAR2-dependent opening of TRPV4 channels, indicating that these proteins were crucial for this signalling process. These results were supported by the qPCR analysis of messenger RNA (mRNA) expression, identifying that all four proteins were expressed in HEK cells, but only treatment with siBUB1, siMAPK13 and siWNK4 caused a significant reduction in the expression of mRNA. Therefore, it was concluded that expressions of the kinases BUB1, MAPK13 and WNK4 are required for the PAR2-dependent opening of TRPV4. The screen of G-proteins and associated signalling molecules identified that treatment of HEK+TRPV4 cells with siGNA13, siGNG8, siPLA2G4A and siPLCXD3 were effective at blocking the PAR2-dependent opening of TRPV4. It was determined by qPCR detection of mRNA expression that GNA13, GNG8 and PLA2G4A but not PLCXD3 were expressed in the tested HEK cells and that treatment with siRNA for GNA13, GNG8 and PLA2G4A caused a significant reduction of mRNA expression, which confirmed that expression of these proteins are required for the PAR2-dependent opening of TRPV4. The previous results identified molecules which were previously unknown to participate in the signalling process between PAR2 and TRPV4. To determine the physiological role of the receptor-dependent opening of TRPV4 channels we investigated the ability of other GPCRs, with evidence of involvement in the opening of TRPV4, to open TRPV4 in this HEK cell model. Therefore we tested pro-inflammatory receptors neurokinin 1 (NK1), bradykinin 1, 2 (BK1, BK2) and prostaglandin receptor EP4 (PGTR4). It was identified that stimulation of NK1 with substance P opened TRPV4, as did stimulation of BK2 with bradykinin. These results indicated that these receptors can open TRPV4 channels in HEK cells and expands the potential to assess receptor-dependent opening of TRPV4 channels in dorsal root ganglion neurons. The ability of adenosine triphosphate (ATP)-dependent GPCRs, called purinergic receptors (P2Y), to open TRPV4 channels were also assessed in HEK293 cells. It was determined that P2Y2 and P2Y11, but not P2Y12, were able to transduce signals required to open TRPV4 when stimulated with their ligand, ATP. The differential ability of these similar receptors; P2Y2, P2Y11 and P2Y12 to open TRPV4 channels demonstrated that stimulation of these receptors in the same HEK cells caused  calcium release from intracellular stores, but the signalling pathway required for GPCR-dependent opening TRPV4 is separate. This evidence confirms earlier experiments in this thesis identifying that GPCR-dependent opening of TRPV4 does not require G-alpha q signalling but has confirmed this with a different GPCR to PAR2. Activation of the muscarinic receptor M3 (M3R) with its ligand acetyl-choline (ACh) stimulated TRPV4 channel opening in the HEK293 cell model. This finding implicated the vascular endothelium as a potential setting for the receptor-dependent opening of TRPV4. The final investigation of this thesis assessed the ability of GPCRs in the vascular endothelium of rat cremaster arterioles to open TRPV4 channels. It was shown that stimulation of TRPV4 with its specific agonist GSK1016790A caused an endothelium-dependent vasodilatation that was abolished by the TRPV4 specific antagonists HC067047 and GSK2193874, and inhibition of small and intermediate calcium-dependent potassium channels (SKCa and IKCa). These results demonstrated that TRPV4-dependent vasodilatation is dependent on endothelial derived hyperpolarising factor (EDH). We then determined that TRPV4 function was altered by shear stress on the endothelium. TRPV4-dependent vasodilatation was sensitised to GSK1016790A after the endothelium had been exposed to shear stress and it was identified that ACh-induced vasodilatation was only sensitive to TRPV4 inhibition after exposure to shear stress. This indicates that the function of TRPV4 was significantly altered in the endothelium with shear stress and that the receptor-dependent opening of TRPV4 required the integration of shear stress into the system. In conclusion, the results presented in this thesis have identified previously unknown signalling molecules in the receptor-dependent opening of TRPV4. It has also identified the complex nature of TRPV4 signalling in the physiological setting of the vascular endothelium, as TRPV4 integrates many different stimuli to regulate its function. Therefore, the molecules crucial to the receptor-dependent opening of TRPV4 identified could prove to be useful targets for future therapeutic intervention of TRPV4 related pathophysiologies

    Pulsed laser deposition for growth of high quality epitaxial garnet films for low threshold waveguide lasers

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    Pulsed laser deposition (PLD) is a mature technique capable of producing extremely high quality epitaxial single crystalline films. We have grown Nd:doped garnet films of GGG (Gd The talk will summarise our progress using conventional (single beam) PLD in thin-film and waveguide growth, using both nanosecond and femtosecond lasers, and also introduce our new directions in tri-beam PLD (three targets, three lasers) for growth of some interesting, complex and perhaps impossible structures, such as Gaussian doping, internal voids and even helically doped structures

    Woodland caribou and forestry in Northern Ontario, Canada

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    Expansion of logging in remote Ontario boreal forest requires mitigation of effects on woodland caribou. Three examples of caribou-forestry interaction are reviewed. In two, caribou were apparently displaced from peripheral portions of their winter range by logging. In the third, caribou disappeared when exposed to: logging in a central third of their winter range; increased deer density, and; a probable increase in predation. In all cases there is no evidence of human harvest. The literature plus experience in Ontario suggest the following mitigative techniques: protection of winter concentration areas, significant calving areas and traditional migration routes from logging; directing timber harvest to forest stands of least value to caribou; restricting disturbance to one large clearcut in a peripheral portion of range rather than dispersing it over a large portion as several small clearcuts; modified site preparation and regeneration, and; restricted road access. Research is required on the effect of forestry on caribou with and without mitigation, and on causes for effects observed

    Characterization of Pro-Inflammatory Flagellin Proteins Produced by Lactobacillus ruminis and Related Motile Lactobacilli

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    peer-reviewedLactobacillus ruminis is one of at least twelve motile but poorly characterized species found in the genus Lactobacillus. Of these, only L. ruminis has been isolated from mammals, and this species may be considered as an autochthonous member of the gastrointestinal microbiota of humans, pigs and cows. Nine L. ruminis strains were investigated here to elucidate the biochemistry and genetics of Lactobacillus motility. Six strains isolated from humans were non-motile while three bovine isolates were motile. A complete set of flagellum biogenesis genes was annotated in the sequenced genomes of two strains, ATCC25644 (human isolate) and ATCC27782 (bovine isolate), but only the latter strain produced flagella. Comparison of the L. ruminis and L. mali DSM20444T motility loci showed that their genetic content and gene-order were broadly similar, although the L. mali motility locus was interrupted by an 11.8 Kb region encoding rhamnose utilization genes that is absent from the L. ruminis motility locus. Phylogenetic analysis of 39 motile bacteria indicated that Lactobacillus motility genes were most closely related to those of motile carnobacteria and enterococci. Transcriptome analysis revealed that motility genes were transcribed at a significantly higher level in motile L. ruminis ATCC27782 than in non-motile ATCC25644. Flagellin proteins were isolated from L. ruminis ATCC27782 and from three other Lactobacillus species, while recombinant flagellin of aflagellate L. ruminis ATCC25644 was expressed and purified from E. coli. These native and recombinant Lactobacillus flagellins, and also flagellate L. ruminis cells, triggered interleukin-8 production in cultured human intestinal epithelial cells in a manner suppressed by short interfering RNA directed against Toll-Like Receptor 5. This study provides genetic, transcriptomic, phylogenetic and immunological insights into the trait of flagellum-mediated motility in the lactobacilli.This work was supported by a Principal Investigator Award (07/IN.1/B1780) from Science Foundation Ireland to PWOT. BAN was the recipient of an Embark studentship from the Irish Research Council for Science Engineering and Technology. TD and KN were supported by the Alimentary Pharmabiotic Centre, funded by Science Foundation Ireland

    Selective Regulation of Aromatase Expression for Drug Discovery

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    Aromatase is a particularly attractive drug target in the treatment of hormone-responsive breast cancer, and aromatase activity in breast cancer patients is greater in or near the tumor tissue compared with the normal breast tissue. Complex regulation of aromatase expression in human tissues involves alternative promoter sites that provide tissue-specific control. Previous studies in our laboratories suggested a strong association between aromatase (CYP19) gene expression and the expression of cyclooxygenase (COX) genes. Additionally, COX selective inhibitors can suppress CYP19 gene expression and decrease aromatase activity. Our current hypothesis is that pharmacological regulation of aromatase can act locally to decrease the biosynthesis of estrogen and may provide additional therapy options for patients with hormone-dependent breast cancer. Two pharmacological approaches are being developed, one approach utilizing small molecule drug design and the second approach involving mRNA silencing technology. The small molecule drug design approach focuses on the synthesis and biological evaluation of a novel series of sulfonanilide analogs derived from COX-2 selective inhibitors. Combinatorial chemistry approaches were used to generate diversely substituted novel sulfonanilides. The compounds suppress aromatase enzyme activity in SK-BR-3 breast cancer cells in a dose and time dependent manner, and structure activity analysis does not find a correlation between aromatase suppression and COX inhibition. Real-time PCR analysis demonstrates that the sulfonanilide analogs decrease aromatase gene transcription in breast cells. Furthermore, the sulfonanilide compounds selectively decrease aromatase gene expression in several breast cancer cells, without exhibiting cytotoxic or apoptotic effects at low micromole concentrations. A ligand-based pharmacophore model for selective aromatase modulation (SAM) by the novel sulfonanilides identified an aromatic ring, two hydrogen bond acceptors, and a hydrophobic function as four key chemical features. In the second approach, short interfering RNAs (siRNA) were designed targeting human aromatase mRNA. Treatment of breast cancer cells with siRNAs targeting aromatase (siAROMs) completely masked the aromatase enzyme activity and resulted in suppression of CYP19 mRNA. Thus, these results suggest that the novel sulfonanilides and the siRNAs targeting aromatase expression may be valuable tools for selective regulation of aromatase in breast cancer

    Cultural Adaptability of Dental Hygiene Students in the United States: A Pilot Study

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    Dental hygiene students should prepare to competently provide services to culturally diverse patients; therefore, this study was conducted as a baseline to determine the cross-cultural adaptability of dental hygiene students. The sample consisted of 188 dental hygiene students attending four culturally diverse dental hygiene programs (N=108) and four non-culturally diverse dental hygiene programs (N=80). The culturally diverse programs randomly selected were located in the southwest, southeast and mid-Atlantic regions of the U.S., and the non-diverse programs were located in the northwest, northcentral, central, and southern regions of the U.S. Any dental hygiene program with students representing four of the five ethnic categories (Caucasian, African American, Hispanic/Latino, American Indian/Alaska Native, and Asian/Pacific Islander) with a culturally diverse student enrollment of 40% or greater, was considered a culturally diverse program; any dental hygiene program enrolling students from only one ethnic category was considered a non-culturally diverse program. Participating students completed the Cross-Cultural Adaptability Inventory (CCAI), a 50-item instrument that measures an individual\u27s cultural adaptability and its four research dimensions: emotional resilience, flexibility/openness, perceptual acuity, and personal autonomy. The instrument does not target one particular cultural, rather it is culture general, meaning the inventory is proficient in assessing all cultures. The unpaired t-test revealed a statistically significant difference, at the 0.05 level, in the overall, emotional resilience, flexibility/openness, and perceptual acuity between the two dental hygiene groups. Data analyses revealed the overall score of the dental hygiene students was lower than the CCAI norm group, which consisted of individuals with cross-cultural experience. The culturally diverse group scored higher than the non-diverse group in emotional resilience but scored lower than the non-diverse group in flexibility/openness and perceptual acuity. There was no statistically significant difference between the culturally diverse and non-culturally diverse groups in the dimension of personal autonomy. Results of the study led to the conclusion that dental hygiene students attending culturally diverse and non-culturally diverse programs possess some qualities such as personal autonomy and self-identity needed for cultural adaptability. The overall CCAI scores were lower than the CCAI norm group suggesting students need cross-cultural education and training. For this reason, it is important that dental hygiene curricula incorporate cross-cultural educational strategies and peer and patient cross-cultural encounters to enable students to develop competency in providing cross-cultural health care. [ABSTRACT FROM AUTHOR

    The effect of relative plasma plume delay on the properties of complex oxide films grown by multi-laser multi-target combinatorial pulsed laser deposition

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    We report the effects of relative time delay of plasma plumes on thin garnet crystal films fabricated by dual-beam, combinatorial pulsed laser deposition. Relative plume delay was found to affect both the lattice constant and elemental composition of mixed Gd3Ga5O12 (GGG) and Gd3Sc2Ga5O12 (GSGG) films. Further analysis of the plasmas was undertaken using a Langmuir probe, which revealed that for relative plume delays shorter than ~200 µs, the second plume travels through a partial vacuum created by the first plume, leading to higher energy ion bombardment of the growing film. The resulting in-plane stresses are consistent with the transition to a higher value of lattice constant normal to the film plane that was observed around this delay value. At delays shorter than ~10 µs, plume propagation was found to overlap, leading to scattering of lighter ions from the plume and a change in stoichiometry of the resultant films
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