Sex determining region Y-box 2 (SOX2) amplification is an independent indicator of disease recurrence in sinonasal cancer.

The transcription factor SOX2 (3q26.3-q27) is an embryonic stem cell factor contributing to the induction of pluripotency in terminally differentiated somatic cells. Recently, amplification of the SOX2 gene locus has been described in squamous cell carcinoma (SCC) of different organ sites. Aim of this study was to investigate amplification and expression status of SOX2 in sinonasal carcinomas and to correlate the results with clinico-pathological data. A total of 119 primary tumor samples from the sinonasal region were assessed by fluorescence in-situ hybridization and immunohistochemistry for SOX2 gene amplification and protein expression, respectively. Of these, 59 were SSCs, 18 sinonasal undifferentiated carcinomas (SNUC), 10 carcinomas associated with an inverted papilloma (INVC), 19 adenocarcinomas (AD) and 13 adenoid cystic carcinomas (ACC). SOX2 amplifications were found in subsets of SCCs (37.5%), SNUCs (35.3%), INVCs (37.5%) and ADs (8.3%) but not in ACCs. SOX2 amplification resulted in increased protein expression. Patients with SOX2-amplified sinonasal carcinomas showed a significantly higher rate of tumor recurrences than SOX2 non-amplified tumors. This is the first study assessing SOX2 amplification and expression in a large cohort of sinonasal carcinomas. As opposed to AD and ACC, SOX2 amplifications were detected in more than 1/3 of all SCCs, SNUCs and INVCs. We therefore suggest that SNUCs are molecularly closely related to SCCs and INVCs and that these entities represent a subgroup of sinonasal carcinomas relying on SOX2 acquisition during oncogenesis. SOX2 amplification appears to identify sinonasal carcinomas that are more likely to relapse after primary therapy, suggesting that these patients might benefit from a more aggressive therapy regime

The antibody-mediated targeted delivery of interleukin-10 inhibits endometriosis in a syngeneic mouse model

BACKGROUND Endometriosis is still a highly underdiagnosed disease, and the current medical and surgical treatment of endometriosis is associated with a high recurrence rate. This study investigates the use of derivatives of the human antibody F8, specific to the alternatively spliced extra-domain A of fibronectin (Fn), for the imaging and treatment of endometriosis. METHODS Immunohistochemistry and immunofluorescence was used to evaluate antigen expression in endometriotic tissue of human endometriosis and of a syngeneic mouse model of the disease. The in vivo targeting performance of a fluorescent derivative of the F8 antibody was assessed by imaging mice with endometriosis using a near-infrared fluorescence imager, 24 h following i.v. injection of the antibody conjugate. Furthermore, the mouse model was used for therapy experiments using two recombinant F8-based immunocytokines [F8-interleukin-10 (IL10) and F8-IL2] or saline for the treatment groups. RESULTS A very strong vascular expression of splice isoforms of Fn and of tenascin-C was observed in human endometriotic lesions by immunohistochemistry and immunofluorescence techniques. After i.v. administration, a selective accumulation of the F8 antibody in endometriotic lesions could be observed in a syngeneic mouse model. These targeting data were used as a basis for therapy experiments with a pro-inflammatory (F8-IL2) and an anti-inflammatory (F8-IL10) cytokine fusion protein of the F8 antibody. The average lesion size in the F8-IL10 treatment group was clearly reduced compared with the saline control group and with the F8-IL2 group, for which no therapeutic effects were observed. CONCLUSIONS The F8 antibody targets endometriotic lesions in vivo in a mouse model of endometriosis and may be used for the non-invasive imaging of the disease and for the pharmacodelivery of anti-inflammatory cytokines, such as IL1

Auctorialité : production, réception et publication de documents numériques

Livre en attente de publication ...Reference points describing the diversification of the field of author's activity considered through the creation of digital documents and the relationships to the readers.Quelques repères de la diversification du champ d'action des auteurs dans leurs relations avec la création des documents numériques et avec leur lectorat. Les outils de l'édition-publication en ligne évoluent en multipliant les réceptacles destinés à recueillir les traces des lecteurs

Illustrations by Rebecca Bootz

In accompaniment with my final portfolio for the senior project class, I will create a supplemental writing for each of the twelve illustrations included in my portfolio, documenting my progress and purpose in creating the illustrations. These writings will include intentions for my work, the meaning behind the artwork, and the processes required to complete the pieces. I intend for these documents to help viewers better understand and appreciate the final illustrations as well as the thought and effort behind them. I will also include research into the artwork and methods of past book illustrators in order to better understand how the process of book illustration has transformed over time and help viewers see the significance of book illustration as a form of art

An approach to system of systems resiliency using architecture and agent-based behavioral modeling

”In today’s world it is no longer a question of whether a system will be compromised but when the system will be compromised. Consider the recent compromise of the Democratic National Committee (DNC) and Hillary Clinton emails as well as the multiple Yahoo breaches and the break into the Target customer database. The list of exploited vulnerabilities and successful cyber-attacks goes on and on. Because of the amount and frequency of the cyber-attacks, resiliency has taken on a whole new meaning. There is a new perspective within defense to consider resiliency in terms of Mission Success. This research develops a new approach of assessing resiliency from the Mission Engineering perspective. Mission Engineering is a new field of systems engineering where the Mission is the system of interest. The Mission requires a SoS with the goal of Mission Success. To the literature, this research contributes an approach to evaluate SoS resiliency based on Mission Success. An agent-based model (ABM) called the SoS architecture resiliency model (SARM) was developed and is a second contribution to the literature. The SARM includes a fuzzy architecture assessor (FAA) as well as SoS behavior represented using fuzzy decision analysis (FDA). The SARM uses DoD architecture framework (DoDAF) views and includes threats. Results show that resiliency can be measured using SARM given the systems, capabilities, and interfaces. Tests with a generic SoS and with a specific SoS provide a proof of concept for the method. To summarize, this research contributes to the literature a method and an executable model for evaluating architecture resiliency as well as the FAA and the FDA”--Abstract, page iii

Compact starburst galaxies in groups of dwarf galaxies

The mechanisms behind the peculiar characteristics of Compact Starburst Galaxies (CSBGs), such as extremely high star formation rates (SFRs) and low gas metallicities, are still poorly understood. They have formed a large fraction of their stellar mass over the last billion years and are true cosmic laboratories for studying the processes that trigger intense star formation activity in galaxies. Based on previous studies about the role of different environments on the extreme properties of CSBGs, we found some of these galaxies in groups of star-forming dwarf galaxies. In the hierarchical framework of galaxy formation and evolution, these groups represent a unique opportunity to investigate the role of interactions and mergers in the stellar mass buildup in low-mass systems. In this monography, we aim to investigate the role of the group environment and gas-rich interactions in the formation and evolution of these CSBGs. We defined a sample of 67 group candidates containing one spectroscopically confirmed CSBG and at least two other starforming galaxies (SFGs) using data from the Sloan Digital Sky Survey. We then carried out observations at the Gemini South and North Observatories, resulting in 12 spectroscopically confirmed groups, which form the sample studied in this work, together with a control sample of 42 isolated CSBGs. We found that the SFRs, oxygen abundances, ionization properties and concentration parameters of isolated and non-isolated CSBGs are similar, indicating that the extreme properties of CSBGs are more related to processes internal to the galaxy than to environmental effects. Despite identifying morphological perturbations in SFG within groups, few signs of these disturbances were identified in CSBGs. Most CSBGs have normal gas metallicities compared to similar galaxies in different environments, but there is a tendency for the CSBG to be the most metal-poor among galaxies in the same group. Finally, by analyzing the star formation history among members of each group, we identified clear signs of synchronous bursts of star formation in some of these groups. Besides, we found that all CSBGs have an old stellar population and had several bursts of star formation since their formation.As características peculiares das Galáxias Starburst Compactas (CSBGs), como altas taxas de formação estelar (sSFRs) e baixa metalicidade, ainda são pouco compreendidas. Estas galáxias formaram grande parte de sua massa estelar nos últimos bilhões de anos e são verdadeiros laboratórios cósmicos para estudar os processos que desencadeiam intensa atividade de formação estelar. Baseando-se em estudos anteriores sobre o papel de diferentes ambientes nas propriedades extremas das CSBGs, encontramos algumas dessas galáxias em grupos de galáxias anãs. No contexto da formação e evolução hierárquica das galáxias, esses grupos de galáxias anãs representam uma oportunidade única para estudar como as interações e fusões contribuem para o crescimento da massa estelar em sistemas de baixa massa. Nesta monografia, investigaremos o papel do ambiente e das interações ricas em gás na formação e evolução das CSBGs. Para isso, definimos uma amostra de 67 candidatos a grupos contendo uma CSBG espectroscopicamente confirmada e pelo menos duas outras galáxias star-forming usando dados do Sloan Digital Sky Survey. Descobrimos que as sSFRs, abundâncias de oxigênio, campos de radiação ionizante e os parâmetros de concentração entre CSBGs isoladas e não isoladas são semelhantes, indicando que as propriedades extremas das CSBGs est˜ao mais relacionadas a processos internos à galáxia do que à efeitos ambientais. Apesar de identificarmos diversas perturbações morfológicas nas galáxias vizinhas às CSBGs, poucos sinais desses distúrbios foram encontrados nas CSBGs em si. Também identificamos uma tendência que aponta que as CSBGs possuem a menor abundância de oxigênio comparado com as outras galáxias de um mesmo grupo. Analisando o histórico de formação estelar entre os membros de cada grupo, identificamos sinais claros de surtos síncronos de formação estelar em alguns desses grupos. Além disso, descobrimos que todas as CSBGs têm uma população estelar velha e tiveram vários surtos de formação estelar desde sua formação