744 resultados para Rho
Resumo:
Many biological materials are known to be anisotropic. In particular, microstructural components of biological materials may grow in a preferred direction, giving rise to anisotropy in the microstructure. Nanoindentation has been shown to be an effective technique for determining the mechanical properties of microstructures as small as a few microns. However, the effects of anisotropy on the properties measured by nanoindentation have not been fully addressed. This study presents a method to account for the effects of anisotropy on elastic properties measured by nanoindentation. This method is used to correlate elastic properties determined from earlier nanoindentation experiments and from earlier ultrasonic velocity measurements in human tibial cortical bone. Also presented is a procedure to determine anisotropic elastic moduli from indentation measurements in multiple directions. © 2001 John Wiley & Sons, Inc. J Biomed Mater Res.
Resumo:
The purpose of this study was to gain a greater understanding of the relationship between athletic success of football and men's basketball and the U.S. News and World Report (USNWR) college rankings. There has been consistent debate among researchers who study institutional quality about whether intercollegiate athletics enhances reputation. This study is similar to other studies attempting to measure the relationship between athletic success and possible indirect benefits to the university from athletics, such as increased admissions applications and increased alumni donations and giving. This study offered a more nuanced model for measuring athletic success, a concept that has been difficult to measure quantitatively. The method used here also measured change over time (in this case, from year-to-year over an eleven year period). The research questions for this study were (a) is there a correlation between athletic success and the USNWR college ranking; and (b) is there a correlation in the change from year-to-year in athletic success with the change from year-to-year in the USNWR college rankings? Spearman Rho correlation and ANOVA tests were used to answer these research questions. The results from the statistical tests demonstrated little correlation between athletic success, whether in football or men's basketball, with the USNWR college rankings. Although the relationships were weak, men's basketball success consistently demonstrated a stronger relationship than football success. This finding differed from what is most often found in the literature, which often favors football success. The ANOVA test results did reveal some results that suggest athletic participation is a factor in the USNWR college rankings. As the debate continues about whether intercollegiate athletics enhances reputation, and as colleges and universities continue spending enormously on athletics, a keener understanding about the possible indirect benefits to the university from athletic programs is needed. The "advertising" provided by spectator sports such as football and men's basketball is often assumed by university leaders to present substantial indirect benefits for the university. However, the existing research along with this study provides little evidence of such opportunities.
Resumo:
Since 2000, the number of living wage ordinances has steadily increased throughout the country. While most of the current research has focused on the beneficial outcomes of living wages, little has been published on their administrative practices. To address this shortcoming, this study focused on the identification of key administrative and political factors involved impacting the implementation of living wage ordinances in Miami-Dade and Broward Counties. The study utilized a triangulation of interviews, surveys, and direct observation. The author conducted interviews of administrators and members of the living wage oversight boards in both counties and observed the monthly meetings held by each county's oversight board from January 2006 to June 2007. These findings were buttressed with a national survey of senior staff in other living wage communities. The study utilized descriptive statistics, Chi Square, Cronbach's Alpha, and Spearman's Rank Correlation Coefficient (Spearman's rho). Interviews indicated that administrators in Dade and Broward are seriously under-staffed and budgeted. Ambiguities in the enabling ordinances have lead to loopholes that undermine implementation and accountability for participating contractors. Survey results showed that policy ambiguity, organizational politics, and a lack of organizational capacity were significant negative factors in the implementation process while an organizational culture emphasizing consistent enforcement was a positive factor. Without the proper inputs, an organization hinders itself from meeting its outputs and outcomes. This study finds that Broward and Miami-Dade Counties do not provide the necessary administrative support to implement a living wage effectively – in stark contrast to the high hopes and strong political support behind their passage. For a living wage to succeed, it first needs an organizational culture committed to providing the necessary resources for implementation as well as transparent, consistent accountability mechanisms.
Resumo:
The purpose of this study was to examine a Higher Education Institution’s (HEI) process of internationalization. The theoretical model developed by Van Dijk and Miejer (1997) was used to review Florida International University (FIU)’s policy, support, and implementation dimensions and determine its position on the Internationalization Cube, and assess how FIU’s international activities fit into its different organizational processes. In addition, the study sought to shed light on student and faculty attitudes toward internationalization. Qualitative and quantitative data were collected from examining organizational documents, interviews, descriptive data on FIU’s international activities using the International Dimension Index, and the Student and Faculty Survey on Internationalization. FIU’s international activities results were analyzed in relation to a panel of experts’ item relevancy index. The Likert-type survey scales’ frequencies and percentages were calculated as well as Spearman Rho correlations between the survey’s three scales and demographic and experiences variables. The study found that FIU is located on position six of a possible eight positions on the Van Dijk and Meijer Internationalization Cube with the following characteristics: Priority Policy, One-Sided Support, and Structured Implementation toward internationalization. The analysis of FIU’s results on international activities showed that FIU exhibits all the activities considered to be strong indicators of internationalization but for position seven placement special attention is needed in the areas of foreign language study, international students, study abroad, faculty movement and involvement in international projects. The survey indicated students and faculty rated the Benefits of Internationalization highly but didn’t perceive strong institutional Support for Internationalization. Faculty age and offshore programs participation; student gender, race/ethnicity and class status; and for both, study abroad and knowledge of students travel grant had significant positive correlations with student and faculty attitudes. The study concluded that an association exists between FIU’s position on the Internationalization Cube and its international activities. Recommendations for policy, implementation, and future studies were made. It was concluded that advancing FIU’s position on the Cube will require adjustments in FIU’s policy, support and implementation dimensions. Differences in student and faculty views toward internationalization should be taken into account when planning internationalization efforts.
Resumo:
This study evaluated the early development and pilot-testing of Project IMPACT, a case management intervention for victims of stalking. The Design and Development framework (Rothman & Thomas, 1994) was used as a guide for program development and evaluation. Nine research questions examined the processes and outcomes associated with program implementation. ^ The sample included all 36 clients who participated in Project IMPACT between February of 2000 and June of 2001, as well as the victim advocates who provided them with services. Quantitative and qualitative data were drawn from client case files, participant observation field notes and interview transcriptions. Quantitative data were entered into three databases where: (1) clients were the units of analysis (n = 36), (2) services were the units of analysis (n = 1146), and (3) goals were the units of analysis (n = 149). These data were analyzed using descriptive statistics, Pearson's Chi-square, Spearman's Rho, Phi, Cramer's V, Wilcoxon's Matched Pairs Signed-Ranked Test and McNemar's Test Statistic. Qualitative data were reduced via open, axial and selective coding methods. Grounded theory and case study frameworks were utilized to analyze these data. ^ Results showed that most clients noted an improved sense of well-being and safety, although residual symptoms of trauma remained for numerous individuals. Stalkers appeared to respond to criminal and civil justice-based interventions by reducing violent and threatening behaviors; however, covert behaviors continued. The study produced findings that provided preliminary support for the use of several intervention components including support services, psycho-education, safety planning, and boundary spanning. The psycho-education and safety planning in particular seemed to help clients cognitively reframe their perceptions of the stalking experience and gain a sense of increased safety and well-being. A 65% level of satisfactory goal achievement was observed overall, although goals involving justice-based organizations were associated with lower achievement. High service usage was related to low-income clients and those lacking in social support. Numerous inconsistencies in program implementation were found to be associated with the skills and experiences of victim advocates. Thus, recommendations were made to further refine, develop and evaluate the intervention. ^
Resumo:
Athletic training is an allied health profession recognized by the American Medical Association requiring certification by examination. There are two routes towards certification as an athletic trainer: attending a university with an accredited athletic training program or with an internship program By 2004, the only route towards certification will be by attending a Commission on Accreditation of Allied Health Education Programs (CAAHEP) or National Athletic Trainers' Association (NATA) accredited athletic training program. CAAHEP looks at passing rates on the NATA Board of Certification (NATABOC) examination when granting accreditation. This study examined characteristics of programs associated with first time passing rates. ^ Directors from 39 CAAHEP or NATA accredited athletic training programs completed a descriptive 17-question survey regarding academic characteristics, faculty characteristics, and program characteristics. Analysis used Spearman's rho correlation coefficient, with significance of p = <.05. Four program directors were interviewed to gather additional insight. ^ There were three program characteristics that showed a significant positive association with first attempt passing rates: the number of full-time and part-time approved clinical instructors (ACIs), and the number of students in the program. Further investigation found a statistically significant association between a low ratio of ACIs to athletic training students and first time passing rates. ACIs are certified athletic trainers (ATCs) who have received special training in order to supervise athletic training students. CAAHEP mandates a 1:8 ratio of ATCs to athletic training student. This study showed that a smaller ratio of ATC to student in combination with ACI training was significantly associated with higher first time passing rates. The number of courses above the required 13 delineated by the Education Council showed a significant negative association with first attempt passing rates. ^ Universities seeking or maintaining accreditation should incorporate characteristics associated with a higher passing rate on the NATABOC examination. Characteristics include utilizing a large number of full-time and part-time ACIs, admitting a large number of students into the program while maintaining a low ACI to athletic training student ratio, and offering curricula that focuses on the 13 courses that have been deemed relevant to the athletic training curriculum by the Education Council. ^
Resumo:
Since 2000, the number of living wage ordinances has steadily increased throughout the country. While most of the current research has focused on the beneficial outcomes of living wages, little has been published on their administrative practices. To address this shortcoming, this study focused on the identification of key administrative and political factors involved impacting the implementation of living wage ordinances in Miami-Dade and Broward Counties. The study utilized a triangulation of interviews, surveys, and direct observation. The author conducted interviews of administrators and members of the living wage oversight boards in both counties and observed the monthly meetings held by each county’s oversight board from January 2006 to June 2007. These findings were buttressed with a national survey of senior staff in other living wage communities. The study utilized descriptive statistics, Chi Square, Cronbach’s Alpha, and Spearman’s Rank Correlation Coefficient (Spearman’s rho). Interviews indicated that administrators in Dade and Broward are seriously under-staffed and budgeted. Ambiguities in the enabling ordinances have lead to loopholes that undermine implementation and accountability for participating contractors. Survey results showed that policy ambiguity, organizational politics, and a lack of organizational capacity were significant negative factors in the implementation process while an organizational culture emphasizing consistent enforcement was a positive factor. Without the proper inputs, an organization hinders itself from meeting its outputs and outcomes. This study finds that Broward and Miami-Dade Counties do not provide the necessary administrative support to implement a living wage effectively – in stark contrast to the high hopes and strong political support behind their passage. For a living wage to succeed, it first needs an organizational culture committed to providing the necessary resources for implementation as well as transparent, consistent accountability mechanisms.
Resumo:
The development and progression of odontogenic tumors have been associated with an imbalance in the activity of growth factors, adhesion molecules, extracellular matrix proteins and their degradation enzymes, angiogenic factors and osteolytic. Some studies have shown that interaction relationships inductive epithelial / mesenchymal determinants of Odontogenesis are mimicked by these tumors. The objective of this research was to investigate the immunolocalization of growth factors (BMP-4 and FGF-8) and Sindecan-1 structural protein in a series of odontogenic tumors presenting different biological behaviors, to contribute to a better understanding of the role of these proteins in tumor development. The sample consisted of 21 of the solid ameloblastoma, odontogenic keratocysts 19 and 14 odontogenic adenomatoid tumors. Increased Sindecan-1 immunostaining was seen in the epithelium of the lesions when compared with mesenchyme. In ameloblastoma and odontogenic keratocysts, this expression was higher than in AOT. Epithelial expression of BMP4 showed quantitatively similar in the three studied lesions; however, when anlisada mesenchymal immunoreactivity, was detected significant higher expression when compared to the ameloblastoma keratocysts. In ameloblastoma, mesenchymal expression was predominantly (p = 0.008), while in keratocyst higher expression in the epithelium was observed (p = 0.046). In all injuries, strong or moderate correlation was observed in the BMP-4 immunoreactivity in the epithelium and mesenchyme. FGF-8, no injury was observed difference between the immunoreactivity in the epithelium or mesenchyme, however in ameloblastoma positive correlation was found (Spearman correlation, rho = 0.857, p <0.001). The results of this study suggest that the three evaluated biomarkers actively involved in the pathogenesis of lesions, especially the expression of ameloblastomas indicating a strong interaction between parenchymal and stromal cells which may contribute to its marked aggressiveness.
Resumo:
The effects of eutrophication on short term changes in the microbial community were investigated using high resolution lipid biomarker and trace metal data for sediments from the eutrophic Lake Rotsee (Switzerland). The lake has been strongly influenced by sewage input since the 1850s and is an ideal site for studying an anthropogenically altered ecosystem. Historical remediation measures have had direct implications for productivity and microbial biota, leading to community composition changes and abundance shifts. The higher sewage and nutrient input resulted in a productivity increase, which led predominantly to a radiation in diatoms, primary producers and methanogens between about 1918 and 1921, but also affected all microorganism groups and macrophytes between about 1958 and 1972. Bacterial biomass increased in 1933, which may have been related to the construction of a mechanical sewage treatment plant. Biomarkers also allowed tracing of fossil organic matter/biodegraded oil contamination in the lake. Stephanodiscus parvus, Cyclotella radiosa and Asterionella formosa were the dominant sources of specific diatom biomarkers. Since the 1850s, the cell density of methanogenic Archaea (Methanosaeta spp.) ranged within ca. 0.5-1.8 x 10**9 cells/g dry sediment and the average lipid content of Rotsee Archaea was ca. 2.2 fg iGDGTs/cell. An altered BIT index (BITCH), indicating changes in terrestrial organic matter supply to the lake, is proposed.
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Um Handover é um momento particularmente crítico num serviço de urgência, comprometendo a segurança e a qualidade dos cuidados (Joint Commission Perspectives, 2012). Para averiguar qual a perceção da qualidade e os fatores relacionados com Handover que ocorre numa sala de emergência, entre os enfermeiros e a equipa de assistência pré-hospitalar, validou-se para a população portuguesa o instrumento de medida Handover Quality Rating Form (HQRF) de Manser et al. (2010), construi-se e validou-se para a população portuguesa o instrumento de medida, Importância da Informação Transmitida Durante o Handover (IITDH) e identificaram-se as dificuldades durante o Handover. Desenvolveu-se um estudo quantitativo, transversal e correlacional e aplicou-se um questionário a 143 enfermeiros do serviço de urgência do Centro Hospitalar de Leira e Centro Hospitalar do Oeste. A consistência interna das escalas HQRF-PT e IITDH e ficou demonstrada por um alfa de Cronbach de 0,830. A HQRF-PT apresentou um score médio de 2,19 (DP=0,58). A IITDH demonstrou que todos os itens apresentam importância elevada, com valores médios compreendidos entre 3,25 e 4,92. As dificuldades durante a realização do Handover foram o “ruído”, o “difícil acesso ao relatório escrito da equipa de assistência pré-hospitalar”, a “escuta ativa perante um doente em deterioração” e o “ambiente stressante”. Por fim, concluímos que a qualidade do Handover é tanto maior quanto menor for a pressão do tempo da pessoa que entrega (rho= -0,244; p≤0,01) e da que assume a responsabilidade do doente (rho= -0,188; p≤0,05), da complexidade (rho=-0,166; p≤0,05) e da incerteza da situação (rho= -0,297; p≤0,05), e que existe uma correlação estatisticamente não significativa entre a perceção da qualidade do Handover e a importância da informação transmitida durante o Handover.
Resumo:
Multiple lines of evidence reveal that activation of the tropomyosin related kinase B (TrkB) receptor is a critical molecular mechanism underlying status epilepticus (SE) induced epilepsy development. However, the cellular consequences of such signaling remain unknown. To this point, localization of SE-induced TrkB activation to CA1 apical dendritic spines provides an anatomic clue pointing to Schaffer collateral-CA1 synaptic plasticity as one potential cellular consequence of TrkB activation. Here, we combine two-photon glutamate uncaging with two photon fluorescence lifetime imaging microscopy (2pFLIM) of fluorescence resonance energy transfer (FRET)-based sensors to specifically investigate the roles of TrkB and its canonical ligand brain derived neurotrophic factor (BDNF) in dendritic spine structural plasticity (sLTP) of CA1 pyramidal neurons in cultured hippocampal slices of rodents. To begin, we demonstrate a critical role for post-synaptic TrkB and post-synaptic BDNF in sLTP. Building on these findings, we develop a novel FRET-based sensor for TrkB activation that can report both BDNF and non-BDNF activation in a specific and reversible manner. Using this sensor, we monitor the spatiotemporal dynamics of TrkB activity during single-spine sLTP. In response to glutamate uncaging, we report a rapid (onset less than 1 minute) and sustained (lasting at least 20 minutes) activation of TrkB in the stimulated spine that depends on N-methyl-D-aspartate receptor (NMDAR)-Ca2+/Calmodulin dependent kinase II (CaMKII) signaling as well as post-synaptically synthesized BDNF. Consistent with these findings, we also demonstrate rapid, glutamate uncaging-evoked, time-locked release of BDNF from single dendritic spines using BDNF fused to superecliptic pHluorin (SEP). Finally, to elucidate the molecular mechanisms by which TrkB activation leads to sLTP, we examined the dependence of Rho GTPase activity - known mediators of sLTP - on BDNF-TrkB signaling. Through the use of previously described FRET-based sensors, we find that the activities of ras-related C3 botulinum toxin substrate 1 (Rac1) and cell division control protein 42 (Cdc42) require BDNF-TrkB signaling. Taken together, these findings reveal a spine-autonomous, autocrine signaling mechanism involving NMDAR-CaMKII dependent BDNF release from stimulated dendritic spines leading to TrkB activation and subsequent activation of the downstream molecules Rac1 and Cdc42 in these same spines that proves critical for sLTP. In conclusion, these results highlight structural plasticity as one cellular consequence of CA1 dendritic spine TrkB activation that may potentially contribute to larger, circuit-level changes underlying SE-induced epilepsy.
Resumo:
Polarization is important for the function and morphology of many different cell types. The keys regulators of polarity in eukaryotes are the Rho-family GTPases. In the budding yeast Saccharomyces cerevisiae, which must polarize in order to bud and to mate, the master regulator is the highly conserved Rho GTPase, Cdc42. During polarity establishment, active Cdc42 accumulates at a site on the plasma membrane characterizing the “front” of the cell where the bud will emerge. The orientation of polarization is guided by upstream cues that dictate the site of Cdc42 clustering. However, in the absence of upstream cues, yeast can still polarize in a random direction during symmetry breaking. Symmetry breaking suggests cells possess an autocatalytic polarization mechanism that can amplify stochastic fluctuations of polarity proteins through a positive feedback mechanism.
Two different positive feedback mechanisms have been proposed to polarize Cdc42 in budding yeast. One model posits that Cdc42 activation must be localized to a site at the plasma membrane. Another model posits that Cdc42 delivery must be localized to a particular site at the plasma membrane. Although both mechanisms could work in parallel to polarize Cdc42, it is unclear which mechanism is critical to polarity establishment. We directly tested the predictions of the two positive feedback models using genetics and live microscopy. We found that localized Cdc42 activation is necessary for polarity establishment.
While this explains how active Cdc42 localizes to a particular site at the plasma membrane, it does not address how Cdc42 concentrates at that site. Several different mechanisms have been proposed to concentrate Cdc42. The GDI can extract Cdc42 from membranes and selective mobilize GDP-Cdc42 in the cytoplasm. It was proposed that selectively mobilizing GDP-Cdc42 in combination with local activation could locally concentrate total Cdc42 at the polarity site. Although the GDI is important for rapid Cdc42 accumulation at the polarity site, it is not essential to Cdc42 concentration. It was proposed that delivery of Cdc42 by actin-mediated vesicle can act as a backup pathway to concentrate Cdc42. However, we found no evidence for an actin-dependent concentrating pathway. Live microscopy experiments reveal that prenylated proteins are not restricted to membranes, and can enter the cytoplasm. We found that the GDI-independent concentrating pathway still requires Cdc42 to exchange between the plasma membrane and the cytoplasm, which is supported by computational modeling. In the absence of the GDI, we found that Cdc42 GAP became essential for polarization. We propose that the GAP limits GTP-Cdc42 leak into the cytoplasm, which would be prohibitive to Cdc42 polarization.
Resumo:
Cryptococcus neoformans is an opportunistic fungal pathogen that causes significant disease worldwide. Even though this fungus has not evolved specifically to cause human disease, it has a remarkable ability to adapt to many different environments within its infected host. C. neoformans adapts by utilizing conserved eukaryotic and fungal-specific signaling pathways to sense and respond to stresses within the host. Upon infection, two of the most significant environmental changes this organism experiences are elevated temperature and high pH.
Conserved Rho and Ras family GTPases are central regulators of thermotolerance in C. neoformans. Many GTPases require prenylation to associate with cellular membranes and function properly. Using molecular genetic techniques, microscopy, and infection models, I demonstrated that the prenyltransferase, geranylgeranyl transferase I (GGTase I) is required for thermotolerance and pathogenesis. Using fluorescence microscopy, I found that only a subset of conserved GGTase I substrates requires this enzyme for membrane localization. Therefore, the C. neoformans GGTase I may recognize its substrate in a slightly different manner than other eukaryotic organisms.
The alkaline response transcription factor, Rim101, is a central regulator of stress-response genes important for adapting to the host environment. In particular, Rim101 regulates cell surface alterations involved in immune avoidance. In other fungi, Rim101 is activated by alkaline pH through a conserved signaling pathway, but this pathway had yet been characterized in C. neoformans. Using molecular genetic techniques, I identified and analyzed the conserved members of the Rim pathway. I found that it was only partially conserved in C. neoformans, missing the components that sense pH and initiate pathway activation. Using a genetic screen, I identified a novel Rim pathway component named Rra1. Structural prediction and genetic epistasis experiments suggest that Rra1 may serve as the Rim pathway pH sensor in C. neoformans and other related basidiomycete fungi.
To explore the relevance of Rim pathway signaling in the interaction of C neoformans with its host, I characterized the Rim101-regulated cell wall changes that prevent immune detection. Using HPLC, enzymatic degradation, and cell wall stains, I found that the rim101Δ mutation resulted in increased cell wall chitin exposure. In vitro co-culture assays demonstrated that increased chitin exposure is associated with enhanced activation of macrophages and dendritic cells. To further test this association, I demonstrated that other mutant strains with increased chitin exposure induce macrophage and dendritic cell responses similar to rim101Δ. We used primary macrophages from mutant mouse lines to demonstrate that members of both the Toll-like receptor and C-type lectin receptor families are involved in detecting strains with increased chitin exposure. Finally, in vivo immunological experiments demonstrated that the rim101Δ strain induced a global inflammatory immune response in infected mouse lungs, expanding upon our previous in vivo rim101Δ studies. These results demonstrate that cell wall organization largely determines how fungal cells are detected by the immune system.
Resumo:
Bud formation by Saccharomyces cerevisiae is a fundamental process for yeast proliferation. Bud emergence is initiated by the polarization of the cytoskeleton, leading to local secretory vesicle delivery and gulcan synthase activity. The master regulator of polarity establishment is a small Rho-family GTPase – Cdc42. Cdc42 forms a clustered patch at the incipient budding site in late G1 and mediates downstream events which lead to bud emergence. Cdc42 promotes morphogenesis via its various effectors. PAKs (p21-activated kinases) are important Cdc42 effectors which mediate actin cytoskeleton polarization and septin filament assembly. The PAKs Cla4 and Ste20 share common binding domains for GTP-Cdc42 and they are partially redundant in function. However, we found that Cla4 and Ste20 behaved differently during the polarization and this depended on their different membrane interaction domains. Also, Cla4 and Ste20 compete for a limited number of binding sites at the polarity patch during bud emergence. These results suggest that PAKs may be differentially regulated during polarity establishment.
Morphogenesis of yeast must be coordinated with the nuclear cycle to enable successful proliferation. Many environmental stresses temporarily disrupt bud formation, and in such circumstances, the morphogenesis checkpoint halts nuclear division until bud formation can resume. Bud emergence is essential for degradation of the mitotic inhibitor, Swe1. Swe1 is localized to the septin cytoskeleton at the bud neck by the Swe1-binding protein Hsl7. Neck localization of Swe1 is required for Swe1 degradation. Although septins form a ring at the presumptive bud site prior to bud emergence, Hsl7 is not recruited to the septins until after bud emergence, suggesting that septins and/or Hsl7 respond to a “bud sensor”. Here we show that recruitment of Hsl7 to the septin ring depends on a combination of two septin-binding kinases: Hsl1 and Elm1. We elucidate which domains of these kinases are needed, and show that artificial targeting of those domains suffices to recruit Hsl7 to septin rings even in unbudded cells. Moreover, recruitment of Elm1 is responsive to bud emergence. Our findings suggest that Elm1 plays a key role in sensing bud emergence.