This paper examines the concept of safety as it encompasses the personal and technological spheres as imagined by a group of active duty service members, veterans, a police officer, and civilians, as well as the agency exercised by those with military or police backgrounds when it comes to safety technology. A group of seventeen individuals took part in a battlefield simulation to test a wearable junctional tourniquet created by ARMR Systems, LLC, an innovative advancement in tourniquet technology. After the simulation, participants were interviewed, surveyed, and took part in a focus group to determine not only product suitability but also to explore the underlying reasons for their recommendations for product changes. Results showed that those with military or police background performed safety rituals prior to duty and exercised agency in the desire to obtain the best possible personal safety devices and technology to be used for themselves and their comrade-in-arms. All participants expressed concerns for their safety in regards to technology in general, specifically, the hacking and use of personal data and what is perceived as lack of governmental oversight. Almost all of the changes to improve product safety, comfort, and utility were adapted. The topics discovered during the course of this research proves a need for safety product testing from an applied anthropological perspective.

L’adhésion, la migration cellulaire et l’environnement stromal sont intimement liés pour garantir l’homéostasie du système immuno-hématopoïétique. Néanmoins, nos connaissances des mécanismes responsables du maintien de ce processus fonctionnel restent fragmentaires. Notre étude a permis de mieux caractériser le stroma ganglionnaire et médullaire dans lesquels nous avons démontré de nouveaux rôles immuno-régulateurs des molécules d’adhésion jonctionnelle JAM-B et JAM-C. Dans la zone T des ganglions lymphatiques, les cellules réticulaires fibroblastiques (FRC) sécrètent des composés de la matrice extracellulaire et des chimiokines homéostatiques, nécessaires à la migration intranodale des lymphocytes T naïfs. La génération de nouveaux anticorps monoclonaux a permis d’identifier une diversité phénotypique et fonctionnelle au sein de la population FRC. L’un d’entre eux reconnaît la Thrombomoduline permettant d’identifier une population de FRC exprimant les protéines JAM-C et PDGFRα. Cette population cellulaire, dénommée FRCDP (Double Positive) sécrète des chimiokines homéostatiques, ce qui la distingue de la population FRCDN (Double Negative). Les souris sauvages traitées avec l’anticorps anti-JAM-C présentent une diminution significative du taux intranodal des chimiokines CXCL12, CCL19, CCL21 affectant la recirculation des cellules T naïves. De façon similaire, les cellules stromales des niches hématopoïétiques fournissent un environnement fonctionnel, nécessaire à l’homéostasie du système hématopoïétique. Les molécules d’adhésion sont connues pour contrôler ces mécanismes. JAM-C est exprimée à la surface des cellules souches hématopoïétiques (CSH) mais son rôle dans l’hématopoïèse reste inconnu. Notre étude montre que la molécule JAM-B est exprimée par l’environnement médullaire et interagit spécifiquement avec JAM-C sur les CSH. Les souris déficientes pour le gène jam-b présentent une diminution du nombre de CSH quiescentes et une réponse accrue aux agents mobilisants, démontrant ainsi que le couple JAM-B/JAM-C est nécessaire au maintien et à la rétention des CSH dans la moelle osseuse. / Homeostasis of the immune and hematopoietic system is dependent of cell adhesion, cell migration and stromal environment. Nevertheless, the molecular mechanisms involved in the crosstalk between hematopoietic and stromal cells have remained elusive. Our studies allowed to better characterize lymph node (LN) and bone marrow (BM) stromal compartments through the demonstration that expression of junctional adhesion molecules (JAM) in these compartments is necessary for the maintenance of immune and hematopoietic homeostasis. In the T cell zone (LN), extracellular matrix and homeostatic chemokines are secreted by fibroblastic reticular cells (FRC) which control naive T cell migration. We have identified new FRC subsets using a monoclonal antibody based approach to identify new cell surface markers of stromal cells. We have found that the FRC population expressing JAM-C, Thrombomodulin and PDGFRα (FRCDP, for Double Positive) secretes homeostatic chemokines such as CCL21, CCL19 and CXCL12. In contrast, FRCDN (Double Negative) that lack JAM-C and Thrombomodulin expression do not. Functionally, we have shown that JAM-C controls the secretion of CCL21, CCL19 and CXCL12 by FRCDP and that anti-JAM-C treated mice exhibit a decrease of intranodal chemokine contents. These results suggest that JAM-C may regulate homeostasis through the control of homeostatic chemokine secretion. We therefore asked the question whether similar function for JAM-C or its ligand JAM-B may be identified in the bone marrow. In the BM, Hematopoietic Stem Cells (HSC) are maintained quiescent and undifferentiated in specific stromal structures called HSC niches. HSC/niche interactions via adhesion molecules and chemokines are known to be active player of HSC homeostasis. Recently, JAM-C expression by HSC has been reported, but its role in hematopoiesis has remained elusive. We have demonstrated that HSC interact with JAM-B expressed by BM stromal cells in a JAM-C dependent manner. Moreover, we have observed a decreased pool of quiescent HSC in jam-b deficient mice. Finally, we have found that jam-b deficient mice exhibit an increase in intramedullary CXCL12 content and an exacerbated response to mobilizing agents. Collectively, these data demonstrate that JAM-B and JAM-C play a dual function in lymph node and bone marrow microenvironments through the regulation of leuko-stromal adhesion and chemokine secretion.

No description available.

The Signal Transducer and Activator of Transcription-3 (Stat3) is a transcription factor that is required for transformation by a number of oncogenes, while a constitutively active form of Stat3 alone is sufficient to induce neoplastic transformation. It was previously demonstrated that cell to cell adhesion causes a dramatic increase in the activity of Stat3 in both normal and tumour cells. This hinted for the first time at the possibility that the role of Stat3 may differ upon cellular confluence. To examine such a mechanism, it is important to evaluate the effect of Stat3 downregulation at different time-points relative to confluence. To examine this, two different approaches for Stat3 downregulation were used: (1) the introduction of high levels of peptidomimetics analogs, which block the Stat3-SH2 domain by using a technique of in situ electroporation. (2) Treatment with two platinum compounds that inhibit Stat3 binding to activated receptors and DNA. The results demonstrated that Stat3 downregulation in vSrc or TAg transformed mouse fibroblast cells or in breast carcinoma lines, induced apoptosis which was more pronounced post-confluence at the time of its peak activity. In contrast, in sparsely growing normal mouse fibroblasts, Stat3 inhibition induced merely a growth retardation. However, in densely growing normal fibroblasts, Stat3 inhibition induced apoptosis. At least in part, apoptosis induced by Stat3 inhibition was mediated by p53, as shown by the resistance to cell death by Stat3 downregulation in colon carcinoma cells, HCT116, where the p53 gene is ablated. Overall, our observations point to the possibility that constitutive activation of Stat3 may lead to tumourigenesis by downregulating wt-53 in cancers that do not have p53 mutations. As a result, targeting Stat3 in cancers with wt-p53 may be a promising therapeutic approach for restoring p53 function, thereby inducing p53-mediated apoptosis. Next, we examined the effect of constitutively activated Stat3 as an oncogene. Stat3C expression in rat F111 fibroblasts induced anchorage independence, but to a lower degree compared to other oncogenes, such as vSrc. Surprisingly Stat3C expression increased gap junction intercellular communication, despite the fact that other oncogenes such as vSrc or vRas effectively block gap junctions. / Thesis (Ph.D, Pathology & Molecular Medicine) -- Queen's University, 2009-04-26 01:09:21.654

This study investigated possible solutions to the current wartime problem of junctional hemorrhaging, or massive traumatic hemorrhaging in non-tourinquetable areas such as the neck, groin, or armpit. Junctional hemorrhaging has been identified as a major contributor to potentially survivable deaths seen on the battlefield today and therefore is a priority for the U.S. armed and coalition forces (Kragh et al., 2011a; Bozeman, 2011). Common tourniquets today are standard issue and carried by soldiers in the military, but are limited to distal extremity trauma. As the battlefield has changes however, trauma has transformed from commonly seen gunshot wounds to more extreme trauma such as dismounted complex blast injuries which typically includes loss of one or more appendages. These newly found situations render the traditional tourniquet ineffective. Thus, the development of a new tourniquet to control hemorrhaging from regions such as the neck, armpit, and groin has been deemed necessary. The development of a new tourniquet for hemorrhage control included market research, preliminary testing to determine design restraints, design ideation, finite element analysis, manufacturing a prototype, and prototype testing. Research and comparisons were done of the strengths and weaknesses of tourniquets already approved by the Food and Drug Administration (FDA). Next, design limitations were found using preliminary testing on a blood-flow replicate model developed by Tracey Cheung. The results from this testing provided a framework for designing a new tourniquet. A new approach to control junction hemorrhaging was then designed, built, and tested on the Cheung model. To verify the design, simplified models were analyzed using finite element analysis. The prototype was then tested and compared against the FDA approved tourniquets, listing the advantages and possible shortcomings.

Pacientes com doença do refluxo não erosiva apresentam sintomas típicos causados pelo refluxo do conteúdo gástrico para o esôfago. Entretanto, estes pacientes não apresentam alterações de mucosa visualizadas à endoscopia. O objetivo deste estudo é caracterizar a expressão de moléculas relacionadas à junção celular (claudinas 1, 3 e 4), da proteína pró-inflamatória Cox-2, da população global de linfócitos (CD45), população de linfócitos T (CD3), linfócitos B (CD20) e natural killer (CD57) em portadores de esofagite de refluxo erosiva e não erosiva. O estudo verificou que quanto mais intensa e crônica a inflamação no epitélio escamoso esofágico, menor a expressão das proteínas juncionais (claudinas 1 e 4), não alterando a expressão da claudina 3. Em relação à Cox-2 o estudo mostra aumento de sua expressão na forma erosiva da doença. Em relação à população de linfócitos, não foi detectada diferença significativa / Patients with non-erosive reflux disease conditions show typical symptons caused by the reflux of the gastric content to the esophagus. However, these patients dont show any alteration on the mucous membrane visualized trhough endoscopy. The aim of this study is to characterize the molecule expression related to the cell junction (claudins 1 , 3 and 4)the Cox 2 pro-inflamatory protein, the general population of (CD45) lymphocytes ,the population of lymphocytes T (CD3),the B (CD20) lymphocytes and the(CD57) natural killer in patients with erosive and non-erosive reflux esophagitis. The study found that the more intense and chronic the inflamation is in the esophageal squamous epithelium, less junction protein expressios (claudins 1 and 4) were found, not altering the 3 expressions of claudin 3. Regarding Cox 2, the study shows increase in its expression in the erosive form of the disease. Regarding the population of lymphocytes, no significant difference was detected

Made available in DSpace on 2016-01-26T12:51:28Z (GMT). No. of bitstreams: 1 vivianecuri_tese.pdf: 3356542 bytes, checksum: 3e315d421d5b2c78bdb72380eb601099 (MD5) Previous issue date: 2010-11-29 / Alcoholism is a public health problem worldwide, involving thousands of men and women, bringing serious consequences as a disease in all organs of the human body, especially the stomach, liver, heart and brain. The consumption of alcoholic beverages for infants and mothers have attracted the attention of researchers in recent decades, with significant. Objective: This study aimed to evaluate the effects of ethanol in the junctional epithelium, adamantine epithelium, epithelium of attached gingiva and periodontal ligament of the upper first molar of the rat, during lactation. Materials and Methods: To this end, we used mice with a day of postnatal life, whose mothers received 20% ethanol in drinking water and rats whose mothers do not received ethanol during the entire lactation. After 21 days, the chicks were sacrificed with anesthetic overdose (Hypnol 3%). The heads were separated and fixed in a solution of "alfac" (alcohol 80% -85 ml, 10 ml of formalin and acetic acid 5-ml), embedded in paraffin and frontal serial sections were stained with hematoxylin and eosin. The cuts were focused light microscope (100x) fitted with a camera lucida. The nuclei of cells from tissue fragments were designed on paper with increased end of 1000x. and 50 nuclei of each structure were outlined with black pencil for later measurement of larger (D) and smaller (d)diameters. Once determined the diameters were estimated karyometric following parameters: geometric mean diameter ratio D / d, perimeter, area, volume, relationship between volume and area, eccentricity, shape coefficient and contour índex. This work also was done using a grid printed on paper. The images were drawn on the grid. In order to assess the volumes and cell cytoplasm, the nucleus / xxiv cytoplasm ratio, the numerical cell density, relation to the external surface / basal layer, the thickness of epithelial layers and the density of the surface was sometimes used the count of the points and sometimes the number of intersections and applied to stereological equations appropriate for each of these variables. All data collected were submitted to non-parametric statistics (Wilcoxon-Mann-Whitney). Results: Histologically, the superior maxillar molar tooth of the rat treated with ethanol was not erupted or partially eruído; the junctional epithelium was reduced and the adamant epithelium was in full function and consists of high palisade cells. The epithelium of attached gingiva was more slender and composed of smaller cells. In the Periodontal ligament was possible to observe bigger and disorganizedfibers. The nuclei of the epithelia studies have shown decreased values after Karyometry, for larger and smaller medium diameters, volume, area, perimeter, and the relation V / A. Stereologically could be observed in the junctional epithelium, adamantine and the attached gingiva, less voluminous cell with scarce cytoplasm leading to a greater number of cells per mm3 of tissue. The disorganized periodontal ligament showed larger fibers with smaller number per mm3. Conclusion: In this study, ethanol resulted in a framework of epithelial hypotrophy, indicating a direct action on the junctional and adamantineepithelium, epithelium of attached gingiva and periodontal ligament. / O alcoolismo é um problema de saúde pública mundial, envolvendo milhares de homens e mulheres, trazendo conseqüências graves como doença em todos os órgãos do corpo do humano, em especial o estômago, o fígado, o coração e o cérebro. O consumo de bebidas alcoólicas por lactantes e lactentes vem despertando a atenção dos pesquisadores, nas últimas décadas, com achados significantes. Objetivo: Este trabalho teve como objetivo avaliar os efeitos do etanol no epitélio juncional, epitélio adamantino, epitélio da gengiva inserida e ligamento periodontal do primeiro molar superior do rato, durante a lactação. Materiais e Métodos: Para tal, foram utilizados ratos com um dia de vida pós-natal, cujas mães receberam etanol a 20% na água do bebedouro e ratos cujas mães não receberam o etanol, durante toda a lactação. Ao final de 21 dias, os filhotes foram sacrificados com sobredosagem anestésica (Hypnol a 3%). As cabeças foram separadas e fixadas em solução de alfac (álcool 80%-85 ml, formalina-10 ml e ácido acético-5 ml), incluídas em parafina e os cortes frontais seriados foram corados com hematoxilina e eosina. Os cortes foram focalizados ao microscópio de luz (100x) munido de uma câmara clara. Os núcleos das células dos tecidos estudados foram projetados sobre papel com aumento final de 1000x. e 50 núcleos de cada estrutura foram contornados com lápis preto para posterior medição dos diâmetros maior (D) e menor (d). Uma vez determinados os diâmetros, foram estimados os seguintes parâmetros cariométricos: diâmetro geométrico médio, relação entre D/d, perímetro, área, volume, relação entre volume e área, xxi excentricidade, coeficiente de forma e índice de contorno. Neste trabalho também, foi utilizada uma grade impressa sobre papel. As imagens obtidas foram desenhadas sobre a grade. Com a finalidade de se avaliar os volumes citoplasmáticos e celular, a relação núcleo/citoplasma, a densidade numérica celular, a relação superfície externa/ camada basal, a espessura das camadas epiteliais e a densidade da superfície, foi utilizada ora a contagem de pontos ora o número de intersecções e aplicadas às equações estereológicas apropriadas para cada uma dessas variáveis. Todos os dados colhidos foram submetidos à estatística não-paramétrica (teste de Wilcoxon-Mann-Whitney). Resultados: Histologicamente, o dente molar do maxilar superior do rato tratado com etanol não estava erupcionado ou então, parcialmente erupcionado; o epitélio juncional estava reduzido e o epitélio adamantino presente estava em plena função e constituído de células altas em paliçada. O epitélio da gengiva inserida era mais delgado e constituído de células menores. No ligamento periodontal foi possível observar fibras desorganizadas e maiores. Os núcleos dos epitélios estudados mostraram valores diminuídos, após cariometria, para os diâmetros maior, menor e médio; volume, área, perímetro e relação V/A. Estereologicamente foi possível observar, nos epitélios juncional, adamantino e da gengiva inserida, células menos volumosas com citoplasma mais escasso levando a um maior número de células por mm3 de tecido. O ligamento periodontal desorganizado mostrou fibras mais volumosas e com menor número por mm3. Conclusões: Neste estudo, o etanol ocasionou um quadro de hipotrofia epitelial, indicando uma xxii ação direta nos epitélios juncional e adamantino, epitélio de gengiva inserida bem como no ligamento periodontal.

No description available.

No description available.

Pacientes com doença do refluxo não erosiva apresentam sintomas típicos causados pelo refluxo do conteúdo gástrico para o esôfago. Entretanto, estes pacientes não apresentam alterações de mucosa visualizadas à endoscopia. O objetivo deste estudo é caracterizar a expressão de moléculas relacionadas à junção celular (claudinas 1, 3 e 4), da proteína pró-inflamatória Cox-2, da população global de linfócitos (CD45), população de linfócitos T (CD3), linfócitos B (CD20) e natural killer (CD57) em portadores de esofagite de refluxo erosiva e não erosiva. O estudo verificou que quanto mais intensa e crônica a inflamação no epitélio escamoso esofágico, menor a expressão das proteínas juncionais (claudinas 1 e 4), não alterando a expressão da claudina 3. Em relação à Cox-2 o estudo mostra aumento de sua expressão na forma erosiva da doença. Em relação à população de linfócitos, não foi detectada diferença significativa / Patients with non-erosive reflux disease conditions show typical symptons caused by the reflux of the gastric content to the esophagus. However, these patients dont show any alteration on the mucous membrane visualized trhough endoscopy. The aim of this study is to characterize the molecule expression related to the cell junction (claudins 1 , 3 and 4)the Cox 2 pro-inflamatory protein, the general population of (CD45) lymphocytes ,the population of lymphocytes T (CD3),the B (CD20) lymphocytes and the(CD57) natural killer in patients with erosive and non-erosive reflux esophagitis. The study found that the more intense and chronic the inflamation is in the esophageal squamous epithelium, less junction protein expressios (claudins 1 and 4) were found, not altering the 3 expressions of claudin 3. Regarding Cox 2, the study shows increase in its expression in the erosive form of the disease. Regarding the population of lymphocytes, no significant difference was detected