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Search Results: 1 - 10 of 267103 matches for " Sara K. B. Cassidy "
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More Than a Pore: The Cellular Response to Cholesterol-Dependent Cytolysins
Sara K. B. Cassidy,Mary X. D. O'Riordan
Toxins , 2013, DOI: 10.3390/toxins5040618
Abstract: Targeted disruption of the plasma membrane is a ubiquitous form of attack used in all three domains of life. Many bacteria secrete pore-forming proteins during infection with broad implications for pathogenesis. The cholesterol-dependent cytolysins (CDC) are a family of pore-forming toxins expressed predominately by Gram-positive bacterial pathogens. The structure and assembly of some of these oligomeric toxins on the host membrane have been described, but how the targeted cell responds to intoxication by the CDCs is not as clearly understood. Many CDCs induce lysis of their target cell and can activate apoptotic cascades to promote cell death. However, the extent to which intoxication causes cell death is both CDC- and host cell-dependent, and at lower concentrations of toxin, survival of intoxicated host cells is well documented. Additionally, the effect of CDCs can be seen beyond the plasma membrane, and it is becoming increasingly clear that these toxins are potent regulators of signaling and immunity, beyond their role in intoxication. In this review, we discuss the cellular response to CDC intoxication with emphasis on the effects of pore formation on the host cell plasma membrane and subcellular organelles and whether subsequent cellular responses contribute to the survival of the affected cell.
Membrane Damage during Listeria monocytogenes Infection Triggers a Caspase-7 Dependent Cytoprotective Response
Sara K. B. Cassidy,Jon A. Hagar,Thirumala Devi Kanneganti,Luigi Franchi,Gabriel Nu?ez,Mary X. D. O'Riordan
PLOS Pathogens , 2012, DOI: 10.1371/journal.ppat.1002628
Abstract: The cysteine protease caspase-7 has an established role in the execution of apoptotic cell death, but recent findings also suggest involvement of caspase-7 during the host response to microbial infection. Caspase-7 can be cleaved by the inflammatory caspase, caspase-1, and has been implicated in processing and activation of microbial virulence factors. Thus, caspase-7 function during microbial infection may be complex, and its role in infection and immunity has yet to be fully elucidated. Here we demonstrate that caspase-7 is cleaved during cytosolic infection with the intracellular bacterial pathogen, Listeria monocytogenes. Cleavage of caspase-7 during L. monocytogenes infection did not require caspase-1 or key adaptors of the primary pathways of innate immune signaling in this infection, ASC, RIP2 and MyD88. Caspase-7 protected infected macrophages against plasma membrane damage attributable to the bacterial pore-forming toxin Listeriolysin O (LLO). LLO-mediated membrane damage could itself trigger caspase-7 cleavage, independently of infection or overt cell death. We also detected caspase-7 cleavage upon treatment with other bacterial pore-forming toxins, but not in response to detergents. Taken together, our results support a model where cleavage of caspase-7 is a consequence of toxin-mediated membrane damage, a common occurrence during infection. We propose that host activation of caspase-7 in response to pore formation represents an adaptive mechanism by which host cells can protect membrane integrity during infection.
In-vivo magnetic resonance imaging of hyperpolarized silicon particles
M. C. Cassidy,H. R. Chan,B. D. Ross,P. K. Bhattacharya,C. M. Marcus
Physics , 2013, DOI: 10.1038/nnano.2013.65
Abstract: Silicon-based micro and nanoparticles have gained popularity in a wide range of biomedical applications due to their biocompatibility and biodegradability in-vivo, as well as a flexible surface chemistry, which allows drug loading, functionalization and targeting. Here we report direct in-vivo imaging of hyperpolarized 29Si nuclei in silicon microparticles by MRI. Natural physical properties of silicon provide surface electronic states for dynamic nuclear polarization (DNP), extremely long depolarization times, insensitivity to the in-vivo environment or particle tumbling, and surfaces favorable for functionalization. Potential applications to gastrointestinal, intravascular, and tumor perfusion imaging at sub-picomolar concentrations are presented. These results demonstrate a new background-free imaging modality applicable to a range of inexpensive, readily available, and biocompatible Si particles.
Youth gender differences in alcohol use: A prospective study of multiple youth assets and the neighborhood environment  [PDF]
Roy F. Oman, Eleni L. Tolma, Sara K. Vesely, Cheryl B. Aspy
Open Journal of Preventive Medicine (OJPM) , 2013, DOI: 10.4236/ojpm.2013.32030

Research has identified factors (assets) that protect youth from engaging in risk behaviors including alcohol use. Very little research has examined asset/nonuse of alcohol associations by youth gender or determined if asset/nonuse of alcohol associations are influenced by the neighborhood environment. The purpose of the study was to determine if multiple youth assets and neighborhood factors are differentially associated with youth nonuse of alcohol by gender. Method: Five waves of data were collected annually from households (N = 1111) randomly selected to participate in the Youth Asset Study. Seventeen assets and 6 neighborhood factors assessed at waves 1 - 4 were analyzed longitudinally using marginal logistic regression to predict nonuse of alcohol at waves 2 - 5. Results: Sample mean age was 14.3 years, 52% female; 39% white, 28% Hispanic, 23% African-American, and 9% other. Numerous assets were prospec- tively associated with alcohol nonuse for females (12 assets) and males (16 assets). Three assets were significantly more protective from alcohol use for males compared to females. Final modeling indicated that three assets were protective from alcohol use for both genders and that one asset was protective only for males. There were no significant associations between the neighborhood variables and nonuse of alcohol, and the neighborhood variables did not influence the asset/nonuse of alcohol associations. Conclusions: Youth assets appear to protect both genders from future alcohol use but males may benefit even more from asset-building prevention programming. Youth alcohol use and alcohol nonuse/asset associations may not be influenced by the neighborhood environment.

Writing community: a humanism curriculum with an academic lens
Sigall K Bell,Edward Krupat,Sara B Fazio,Stephen Pelletier
Medical Education Development , 2011, DOI: 10.4081/med.2011.e4
Abstract: Explicit teaching of humanism is a goal of education reform, but specific strategies to do so are limited. The authors developed a longitudinal third-year medical student curriculum combining reflective and academic writing with literary reading and reflection to i) improve writing skills, ii) enhance scholarly activities, and iii) foster humanism in patient care. From 2005-2007, 24 third year Harvard Medical School (HMS) participated in a writing program at this hospital. All students completed pre/post surveys and qualitative assessments of the writing program. Students felt better-equipped to access resources (P=0.03), conduct a literature review (P<0.01), and understand the meaning of the patient’s narrative (P<0.01) after the program. Their total survey score (assessing writing skills and attitudes) was also significantly higher after the program (P=0.02). Students described positive effects of writing on self-acceptance, curiosity, and patient-centered care. Of the 24 students, 4 published 5 manuscripts in peer-reviewed journals in the first 2 years of the program. A writing curriculum focusing on humanism is feasible, and can enhance comfort with writing, early publication successes, self-awareness, and perceived humanistic qualities in the interactions of third-year students with their patients.
Family Background and Environment, Psychological Distress, and Juvenile Delinquency  [PDF]
Tony Cassidy
Psychology (PSYCH) , 2011, DOI: 10.4236/psych.2011.29142
Abstract: The relationship between youth offending and family background is still unclear in the literature. This study explored the role of family factors and psychological distress in relation to delinquency and youth offending to try and explicate the relative importance of family structure, family relations, and psychological distress. The study used the Brief Symptom Inventory, the Family Environment Scale, and the Delinquency Scale in a structured interview format to measure psychological distress, family structure and relations, and levels of youth offending, in 219 older children and adolescents aged between 12-17 years living in areas associated with high levels of youth offending in the UK. Analysis involved correlations, hierarchical multiple regression and analysis of variance. Family relations were the best predictors of delinquency and were also correlated with psychological distress. The relationship between delinquency and psychological distress indicated that participants with more psychological distress were less likely to be involved in criminal behaviour. The study supports the conclusion that youth offending and psychological distress are both influenced by a range of factors in the family, but may be unrelated to each other.
Development of a Curved, Stratified, In Vitro Model to Assess Ocular Biocompatibility
Cameron K. Postnikoff, Robert Pintwala, Sara Williams, Ann M. Wright, Denise Hileeto, Maud B. Gorbet
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0096448
Abstract: Purpose To further improve in vitro models of the cornea, this study focused on the creation of a three-dimensional, stratified, curved epithelium; and the subsequent characterization and evaluation of its suitability as a model for biocompatibility testing. Methods Immortalized human corneal epithelial cells were grown to confluency on curved cellulose filters for seven days, and were then differentiated and stratified using an air-liquid interface for seven days before testing. Varying concentrations of a commercial ophthalmic solution containing benzalkonium chloride (BAK), a known cytotoxic agent, and two relevant ocular surfactants were tested on the model. A whole balafilcon A lens soaked in phosphate buffered saline (BA PBS) was also used to assess biocompatibility and verify the validity of the model. Viability assays as well as flow cytometry were performed on the cells to investigate changes in cell death and integrin expression. Results The reconstructed curved corneal epithelium was composed of 3–5 layers of cells. Increasing concentrations of BAK showed dose-dependent decreased cell viability and increased integrin expression and cell death. No significant change in viability was observed in the presence of the surfactants. As expected, the BA PBS combination appeared to be very biocompatible with no adverse change in cell viability or integrin expression. Conclusions The stratified, curved, epithelial model proved to be sensitive to distinct changes in cytotoxicity and is suitable for continued assessment for biocompatibility testing of contact lenses. Our results showed that flow cytometry can provide a quantitative measure of the cell response to biomaterials or cytotoxic compounds for both the supernatant and adherent cell populations. As a specifically designed in vitro model of the corneal epithelium, this quantitative model for biocompatibility at the ocular surface may help improve our understanding of cell-material interactions and reduce the use of animal testing.
Effective Truncation of a Student’s t-Distribution by Truncation of the Chi Distribution in a Chi-Normal Mixture  [PDF]
Daniel T. Cassidy
Open Journal of Statistics (OJS) , 2012, DOI: 10.4236/ojs.2012.25067
Abstract: A Student’s t-distribution is obtained from a weighted average over the standard deviation of a normal distribution, σ, when 1/σ is distributed as chi. Left truncation at q of the chi distribution in the mixing integral leads to an effectively truncated Student’s t-distribution with tails that decay as exp (-q2t2). The effect of truncation of the chi distribution in a chi-normal mixture is investigated and expressions for the pdf, the variance, and the kurtosis of the t-like distribution that arises from the mixture of a left-truncated chi and a normal distribution are given for selected degrees of freedom <5. This work has value in pricing financial assets, in understanding the Student’s t--distribution, in statistical inference, and in analysis of data.
Suicide, Mental Illness and Maori People  [PDF]
Said Shahtahmasebi, Bernadette Cassidy
Open Journal of Social Sciences (JSS) , 2014, DOI: 10.4236/jss.2014.28014
Abstract: Globally, authorities and “experts” continually assert that suicide is a major public health concern and it is preventable. However, decades of suicide prevention strategies have seen “more of the same” action plans but no change in the upward suicide trend. Therefore, the current suicide prevention model is less relevant to indigenous and minority populations with a high suicide rate. Current suicide statistics for Maori, New Zealand’s indigenous population are unacceptably high. The Maori suicide rate is about 19 per 100,000 roughly averaging about 104 deaths per year over the last six years. Maori claim that before colonisation suicide was non-existent. There is certainly evidence to support such a claim. e.g., historical suicide data suggested that the number of Maori youth suicide deaths was less than five until the 1970s and 1980s. Maori now have the dubious honour of having the highest rates of mortality and morbidity outcomes, including higher rates of suicide. Neither Maori nor the authorities responded with an action plan when suicide numbers spiked in 1960 and 1967. Subsequently, the number of suicides rose sharply to over one hundred where they stayed. It is plausible that exposure to Western ideals as well as social insensitivity to Maori beliefs and needs may have led to a cultural dealignment during the1960s and 1970s. This cultural shift also may be due to the application of a Western model of suicide prevention based on mental illness. The Western model does not work in preventing suicide and conflicts with indigenous cultures.
How Far Can a Biased Random Walker Go?  [PDF]
Zhongjin Yang, Cassidy Yang
Journal of Applied Mathematics and Physics (JAMP) , 2015, DOI: 10.4236/jamp.2015.39143
Abstract: The random walk (RW) is a very important model in science and engineering researches. It has been studied over hundreds years. However, there are still some overlooked problems on the RW. Here, we study the mean absolute distance of an N-step biased random walk (BRW) in a d-dimensional hyper-cubic lattice. In this short paper, we report the exact results for d = 1 and approximation formulae for d ≥ 2.
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