VictorJuiz/thesis huggingface dataset:
The cellular and molecular mechanisms regulating oxidative stress-induced priming of the macrophage: the role of the Src family of tyrosine kinases

Civilian trauma remains a leading cause of disability and mortality in North America. Late deaths are related to the development of multiple organ failure in up to two-thirds of these patients. Many studies suggest that the global ischemia-reperfusion resulting from resuscitated hemorrhagic shock predisposes patients to organ injury by priming for an exaggerated immune response to a delayed inflammatory stimulus. The synergistic effect of sequential stimuli has been termed the "two-hit" hypothesis for the development of organ injury in trauma patients. Oxidative stress generated during ischemia/reperfusion injury has been shown to augment cellular responsiveness. While oxidants are themselves known to induce several intracellular signaling cascades, the affect oxidants have on signaling pathways initiated by other inflammatory stimuli remains poorly elucidated. Previous work suggested that oxidants can prime alveolar macrophages for increased NF-kappaB translocation in response to treatment with LPS. Since oxidants are known to stimulate the Src family of tyrosine kinases, we hypothesized that the oxidants might contribute to augmented NF-kappaB translocation by LPS via the involvement of Src family kinases. Together, these studies provide a novel potential mechanism whereby oxidants might prime alveolar macrophages for altered responsiveness to subsequent inflammatory stimuli and suggest different cellular targets, such as the Src kinase family, for immunomodulation following ischemia/reperfusion. These findings suggest oxidative stress might divert LPS signaling along an alternate signaling pathway. Further studies demonstrated that the Src-dependent pathway induced by oxidant pretreatment activated the of PI3-kinase/Akt pathway. Involvement of this pathway appears to be independent of traditional LPS signaling. To model macrophage priming in vitro, the murine macrophage cell line, RAW 264.7, was first incubated with various oxidants and then exposed to low dose LPS. These studies show that oxidant stress can augment macrophage responsiveness to LPS as evidenced by earlier and increased NF-kappaB translocation. Inhibiting Src family kinases either pharmacologically using PP2 or through a molecular approach by cell transfection with carboxyl-terminal Src kinase (Csk) prevents the augmented LPS-induced NF-kappaB translocation caused by oxidants. Interestingly, while inhibiting Src kinases prevented the LPS-induced NF-kappaB translocation in oxidant-treated macrophages, the strategy had no effect on NF-kappaB translocation caused by LPS in the absence of oxidants. Using our in vivo rodent model of hemorrhagic shock/resuscitation we found oxidant stress generated during shock/resuscitation in vivo activates Src family kinases in alveolar macrophages. Inhibiting Src activation by PP2 attenuates alveolar macrophage priming for increased LPS responsiveness following hemorrhagic shock resulting in a modest reduction in lung injury.
Determining the effect of a matrix metalloproteinase-inhibiting material on degradable biomaterial implants

Implanted tissue engineered constructs trigger a foreign body reaction (FBR). The FBR can diminish the construct's therapeutic effects. Matrix metalloproteinases (MMPs) are expressed in the FBR and are possible targets for control. It was hypothesized that a hydroxamate-based MMP-inhibiting (MI) polymer would alter the FBR to a degradable implant (construct) and delay its remodelling in vivo. Constructs were co-implanted subcutaneously in mice with MI polymer or poly(methyl methacrylate) controls. Visual, mass, volume and mechanical property data suggested MI polymer delayed construct remodelling. MI treatment appeared to reduce MMP-2 and -9 activities in the implant site at day 10. Surprisingly, MMP-2, -8, tissue inhibitor of metalloproteinase-I and inflammatory cell concentrations were higher with MI treatment. In this model and context, MI polymer appears pro-inflammatory and new methods for deploying the polymer should be explored. It was concluded that strategies focusing on inhibiting MMPs while ignoring their generation might not be successful.
The effect of early phonics instruction on children's invented spelling and an examination of the relation between invented spelling and current and later reading achievement

The current research was comprised of two studies. The purpose of Study 1 was to explore the effect of a commercially available phonics program (Jolly Phonics) on young children's invented spelling ability. In Study 1, the developmental sophistication of the spelling responses of children exposed to Jolly Phonics was compared to that of control children who were not exposed to the program or an equivalent. Results indicated that, across all three early elementary grades examined (junior kindergarten, senior kindergarten, and Grade 1), children in experimental classes produced developmentally superior spelling responses than controls. In addition, children who were exposed to Jolly Phonics for 2 years produced developmentally superior spelling responses than children exposed to the program for 1 year only. The purpose of Study 2 was to explore the relation between invented spelling and reading ability in several early and later elementary grades. It was also of interest to compare the extent to which invented spelling scores, standard spelling scores (i.e., the traditional method of scoring spelling responses on a right or wrong basis), and scores on a commonly used phonological awareness measure (i.e., the TAAS; Rosner, 1971) were associated with and predictive of academic achievement. Results indicated that, across all early (junior kindergarten, senior kindergarten, and Grade 1) and later (Grades 3, 5, and 6) elementary grades examined, invented spelling was moderately associated with measures of reading ability. Invented spelling was found not to differ from standard spelling in terms of its association with reading ability but was found to be more highly associated with reading ability than the TAAS. In terms of predicting later academic achievement, invented spelling measured in kindergarten was found to predict a substantial amount of variance in Grade 5 academic achievement measures. In contrast, the TAAS measured in Grade 1 was found to predict a substantial amount of variance in Grade 6 academic achievement. The results of Studies 1 and 2 are discussed in reference to early elementary classroom practice and assessment of phonemic awareness skills.

Keywords: Reading, Phonetic method
Phonetics, Study and teaching (Primary)
Children, Reading
Language arts (Primary)
Word recognition
English language, Orthography and spelling
Role of the thiazide-sensitive sodium chloride cotransporter gene in primary hypertension associated with hypercalciuria

Hypertension is a common disease with major public health implications and complex genetic background. Abnormalities in renal sodium handling is a central feature of the pathogenesis of essential hypertension. The renal thiazide-sensitive sodium chloride cotransporter (TSC) is a major sodium and chloride transporter in the distal nephron. It is known to indirectly influence renal calcium handling and is involved in monogenic diseases that feature arterial hypotension or hypertension We hypothesize that genetic variations in the TSC gene are important in the pathogenesis of salt-sensitive essential hypertension associated with hypercalciuria through increased sodium transport. The objectives of this thesis are to: (1) test for linkage of hypertension and hypercalciuria to the chromosomal region harbouring the TSC gene, (2) search for genetic variants in the coding region of the gene and to study their effect on TSC function, and (3) test for an association of hypertension and hypercalciuria with intragenic marker alleles in the gene. Family based analysis did not show association to hypertension or hypercalciuria, emphasizing the need for further studies to resolve the controversy of the TSC's role in hypertension. Linkage analysis of families with hypercalciuric probands and a family history of hypertension, using five microsatellite markers spanning a 10 cM region on chromosome 16q13, demonstrated suggestive linkage to the TSC gene locus. We have found four non-synonymous single nucleotide polymorphisms by screening the coding region of the TSC gene in these families, and demonstrated that one of the variants causes increased sodium transport when expressed in a heterologous oocyte expression system. This variant may contribute to elevated blood pressure in individuals with this genetic abnormality.
Dressing the wounds: an investigation into the experiences of middle school educators with students who self-injure

The acts of cutting, hitting, biting or burning one's own body have become increasingly prevalent amongst adolescents. These behaviours have been termed self-injury but are also known as deliberate self-harm, self-abuse or self-mutilation. The onset of self-injuring behaviours often coincides with early adolescence, placing middle school educators in a prime position to prevent or intervene in the employment of them. Unfortunately there is little research to support those educators when they are faced with the challenge of responding to a student who is, or may be, self-injuring leaving both them and their students at a disadvantage. Driven by the main question, "What experiences have educators had with urban middle school students who self-injure?" this inquiry has begun to address this omission. Through semi-structured interviews and document analysis, the experiences of six educators who worked in Canadian middle schools with students who self-injured were explored. Research findings were coded thematically and then juxtaposed with the current literature on self-injury and with documents pertaining to the legal obligations and ethical guidelines for educators. In highlighting areas of resonance and dissonance four areas of interest emerged: (i) the in-depth understanding of self-injury the participants held, (ii) the evolving nature of self-injury in schools, which included flaunting the behaviours, group engagement and a contagion effect, (iii) intervention strategies both undertaken and proposed by participants along with perceived obligations, and (iv) potential approaches to prevention. Implications for future research and practice were also suggested throughout this process. The overall findings of this study suggest that self-injury has become a pervasive behaviour educators are required to contend with in middle schools, which requires further investigation.
The Canadian Anti-vaccination Leagues, 1872--1892

This thesis is both an intellectual and social history of the strategies, activities, arguments and purported impact of the two Anti-vaccination Leagues that were active in Canada between 1872 and 1892. This work situates anti-vaccination reasoning within a broader framework of the Canadian experiences with smallpox, vaccine technology and vaccination science and medicine. The findings indicate that the standard depiction of anti-vaccinationism as part of a sanitary movement that rejected a 'reductionist' bacteriological system of medicine for a more holistic approach is overstated. The rejection or acceptance of a particular medical system did not strictly accord with the rejection or acceptance of vaccination. Some eclectic and homeopathic physicians in Canada accepted vaccination while regular physicians could and did reject it. In turn, anti-vaccinationists employed contemporary empirical methods and modes of analysis in their analysis of vaccine data. Their analysis of the empirical data is distinguishable from pro-vaccinationists only in its rejection of the principles of vaccination. Anti-vaccinationists felt that vaccine-immunity had not been demonstrated and this had serious consequences for how they read and understood empirical data. They argued that compulsory vaccination was a class-based legislation whose function was to exert control over the working classes. These arguments were successfully taken up by French nationalists in Montreal who used vaccination to promote discord between the French and English. By disseminating reports of serious side-effects from public vaccinators' vaccine, questioning the theoretical and empirical basis for vaccine programs and by adding the cultural argument that compulsory vaccination was a part of paternalistic and monopolistic medical profession, anti-vaccinationists both stimulated and reflected the wide-spread resistance to compulsory vaccination in the period of this study.
In vitro and in vivo modeling of human hematopoietic malignancies

The hematopoietic system produces appropriate levels of blood cells over an individual's lifetime through a careful balance of differentiation, proliferation and self-renewal. The deregulation of these processes leads to the development of malignancies including myeloproliferative disorders (MPDs) and acute myeloid and lymphoid leukemias (AML and ALL, respectively). A prerequisite for targeted therapies is an understanding of the processes which subvert the developmental program of the hematopoietic system in these diseases. This involves identifying the cell of origin and the sequence of molecular lesions required to generate cells capable of initiating disease, as well as phenotypically characterizing the cells responsible for sustaining the malignant clone in vivo. Significant progress has been made in these areas, particularly through the identification of recurrent genetic alterations, such as activating mutations of the Janus kinase 2 (JAK2) gene in MPDs and translocations involving the mixed-lineage leukemia (MLL) gene in acute leukemias. Characterization of these oncogenes has been performed using cell lines and mouse models; however, to precisely model the development of hematopoietic malignancies, it is necessary to perform similar studies in primary human cells. To this end, we have developed an experimental system where genetic hits are introduced into lineage-depleted human umbilical cord blood (Lin-CB) by retroviral-mediated oncogene overexpression. Using this approach, we have shown that TEL-JAK2, a constitutively active variant of JAK2, drives erythropoietin-independent erythropoiesis in vitro and induces the rapid development of myelofibrosis in vivo. This work indicated that activated JAK2 signaling is sufficient to drive MPD-associated disease processes and also established the feasibility of utilizing xenotransplantation systems to develop models of human hematopoietic malignancies. Using a similar approach, we subsequently demonstrated that Lin-CB cells expressing MLL fusion genes reproducibly generate AML and B-ALL in vivo. Serial transplantation showed that these diseases were sustained by leukemia-initiating cells (L-ICs) that undergo phenotypic evolution, establishing that L-ICs in established disease need not resemble the cell of origin. Moreover, some L-ICs could initiate both myeloid and B-lymphoid disease, and in these instances, microenvironmental cues could select for the resulting leukemia lineage. Collectively, the models described here provide numerous insights into the pathobiology of human hematopoietic malignancies.
Legal scholarship in Reich and Republic: Ernst Forsthoff, Theodor Maunz and Hans Peter Ipsen

This article examines the writings and biographies of Ernst Forsthoff, Theodor Maunz, and Hans Peter Ipsen. Forsthoff and Maunz became professors in 1933, Ipsen in 1940. To varying degrees, all three were supporters of the Nazi regime, but returned to positions of influence in German constitutional and administrative law scholarship after 1945. The article compares the writings of Forsthoff, Maunz and Ipsen during and after the Third Reich, analysing both form and content and examining topics such as support for policies of the national socialist state; the role of rule-of-law principles; anti-Semitism in scholarly writings; and retention of National Socialist patterns of thought after 1945. The article concludes by assessing the integration of supporters of the national socialist regime into post-war democratic reconstruction, providing insights that may also be applicable to later-day transitional democracies.

Keywords: Nationalism and literature, Germany
National socialism, Germany
Constitutional law, Germany
Administrative law, Germany
An evaluation of the role of one community college in immigrant settlement

This qualitative study examines the experiences of immigrant graduates from one community college in the areas of recognition of prior experience and credentials, admission, retention, graduate placement, and their perceptions regarding the value of the college experience in assisting them with settlement in Canada. Quantitative data were also collected relating to salary so that comparisons could be made with previous studies in this area. Sociological frameworks developed by Hardiman and Jackman (1996), Rawls (1971), and Mitchell and Shillington (2002) are drawn upon to direct the research and interpret the findings of this study with an emphasis on social justice. In addition, an expert panel was utilized to guide the refinement of the research questions, comment upon the findings and evaluate results. Interviews were conducted with thirty-seven participants to gain their observations and insights as to the role the college played in assisting them with settlement in Canada. The findings suggest that the college participating in this study has met or exceeded participants' expectations in the areas of overall college experience, searching for employment (time and type), potential for career advancement, and marketability of graduates. Further, the findings of this study indicate that the college has had a positive impact on both community participation and settlement as it relates specifically to employment. However, the findings also indicate that the college has done little to facilitate settlement in the community of those interviewed. Finally, not withstanding participants' reported successes in searching for employment, the relatively low wages, precarious nature of the work secured by those interviewed, and an overall deterioration in earnings calls into question employers' apparent willingness to operate in a manner which contributes to maintaining an environment of social and economic justice within Canada. Federal and provincial governments, social organizations and many employers have become aware of the multiple issues immigrants experience upon arrival in Canada. Indeed, many of these groups have begun to work together putting programs and services in place to help. This study contributes to gaining a better understanding of the challenges immigrants may face in the settlement process and offers recommendations to enhance one college's efforts in this area. (PsycINFO Database Record (c) 2016 APA, all rights reserved)
Smurfs are E3 ubiquitin protein ligases that inhibit the transforming growth factor beta signalling pathway

The Transforming Growth Factor Beta (TGFβ) Signalling Pathway is important for development, differentiation, and homeostasis. This pathway is activated upon ligand binding to heteromeric receptors on the cell surface, which in turn activate a cascade of downstream intracellular events. The intracellular transducers of the signal are known as Smads. These proteins are classified into three groups; Receptor regulated Smads, Common Smads, and the Inhibitory Smads. The Receptor regulated Smads together with the Common Smads transduce the signal, whereas, the Inhibitory Smads block the signal. In addition to the Inhibitory Smads, other proteins have been shown to actively participate in terminating the signal. I found that two of these proteins, called Smurfs (for Smad ubiquitination regulatory factors), are part of the Ubiquitination pathway. Smurf1 and Smurf2 are E3 ubiquitin protein ligases that specifically ubiquitinate certain components of the TGFβ signal transduction pathway. The ubiquitination of these proteins results in their destruction by the cell's proteolytic degradation machinery; therefore Smurf1 and Smur2 can function to inhibit TGFβ superfamily signalling. I suggest that Smurf-mediated turnover of key signalling components is an effective way to limit and terminate the TGFβ signalling pathway.
Creating a community-specific environmental education website

In this thesis, the growth of environmentalism in the United States and the impediments to institutionalized environmental education are explored. The need to unite science education with environmental education and the use of the Internet in such an endeavour are explained. The specific case of environmentalism in Indiana and the status of environmental education within the state are presented to provide context for the creation of a community-specific environmental education website, BioMuncie (http://www.biomuncie.org/ ), which focuses on Muncie, Indiana. The impact of the site on the general Muncie community over the course of its first six months and its growth in response to community needs is recounted and personal reflections shared. Issues of advocacy, quality and access are considered as the construction of this community website is discussed. Finally the educational and environmental merit of the site is considered. Its strengths and limitations serve as guides for future development.

Keywords: Environmental education
Environmental education, Computer network resources
Environmental education, Indiana
Community education, Indiana