Ziel dieser Studie war es, die Häufigkeit der Expression von EGFR, HER-2 sowie COX-2 im Zervixkarzinom zu eruieren. Dabei galt es herauszufinden, ob Unterschiede hinsichtlich des Nachweises dieser drei, möglicherweise therapeutisch relevanten Moleküle zwischen den primären, nicht vortherapierten und operierten Karzinomen und den multimodal vorbehandelten Rezidiven gab. In der vorliegenden retrospektiven Arbeit wurden 45 TMMR-operierte Primärtumoren und 28 LEER-operierte Rezidivtumoren der Universitätsfrauenklinik Leipzig (Triersches Institut) einbezogen und zusätzlich hinsichtlich der prognostischen Überlebensanalyse durch das Tumorstadium, Lymphknotenmetastasen und Rezidivauftreten sowie histologischer Charakteristika untersucht. Dazu wurden Tissue - Microarrays angefertigt mit anschließender immunhistochemischer Untersuchung dieser. Die Ergebnisse zeigten, dass die TMMR-Operation die Überlebensprognose signifikant verbessert, denn lediglich bei den LEER-therapierten Rezidivtumoren erlitten die Patientinnen sowohl Fernmetastasen als auch erneute Rezidive. Weder die Expression der drei untersuchten Moleküle noch die histopathologischen Parameter haben eine prognostische Relevanz. Es gibt keine signifikanten Zusammenhänge zwischen der Häufigkeit der Expression von EGFR, HER-2 sowie COX-2 und Primär-, bzw. Rezidivtumoren, sodass diese Moleküle keine Targets für eine individualisierte, zielgerichtete Therapie beim Zervixkarzinom darstellen.

Objetivos: Determinar hallazgos estructurales o funcionales ecocardiográficos en pacientes recuperados de infección SARS-CoV-2. Materiales y métodos: Estudio observacional transversal, que incluyó pacientes trabajadores de un hospital nacional COVID, estudiados entre 3 a 6 meses luego del diagnostico de infección SARS-CoV-2. La exploración ecocardiográfica se desarrolló de forma sistemática e incluyó las modalidades convencionales. Resultados: Se incluyeron 65 casos con infección-CoV-2, la edad promedio fue 37.7 años, la obesidad resultó la comorbilidad mas frecuente (13.8%) y la presentación clínica leve fue la de mayor prevalencia (84.6%). Las medias del diámetro diastólico y la fracción de eyección ventrículo izquierdo fueron 42mm y 57% respectivamente. Así mismo la media del diámetro basal del ventrículo derecho fue de 31mm, de la fracción de acortamiento 44% y en todos los casos se reportó probabilidad de hipertensión pulmonar como baja. No se encontró efusión pericárdica en ninguno de los casos. Conclusiones Los pacientes recuperados de infección SARS-CoV-2, no presentan alteraciones estructurales ni funcionales en la exploración ecocardiográfica convencional.

No description available.

No description available.

This thesis presents new 450$\mu$m and 850$\mu$m observations of NGC3627 taken with the new SCUBA-2 with the main goal of trying to better understand the properties of gas and dust in the interstellar medium of NGC3627. We determined properties of the cold component of NGC3627's spectral energy distribution (SED) using dust models given by the Planck Collaboration, by Li and Draine, and allowing the emissivity index to be treated as a free parameter. Fitting the SED required the use of 100$\mu$m, 160$\mu$m, 250$\mu$m, 350$\mu$m, and 500$\mu$m data from the KINGFISH survey. Each of the KINGFISH observations have been passed through an extended emission filter in order to match the SCUBA-2 observations. The best fit temperatures and emissivity indices agreed with the results found in other recent studies, but our fitted masses were smaller than those of other studies due to differences in the fitted temperature and observed fluxes. After the properties of the dust emission were calculated, we implemented a method to determine the amount of molecular hydrogen present in NGC3627. The method we used involves finding a CO-to-H$_2$ conversion factor that minimizes the scatter present in dust-to-gas mass ratio. We used CO J=2-1 from the HERACLES survey and CO J=1-0 from the Nobeyama 45-m telescope to act as our molecular tracer, and HI observations of NGC3627 from the THINGS survey. The results from minimizing the dust-to-gas ratio scatter give low $\alpha_{CO}$ values, that are normally associated with U/LIRGs. The low $\alpha_{CO}$ values can be attributed to the treatment of the error associated with reported $\alpha_{CO}$. The uncertainties for $\alpha_{CO}$ reported in this thesis are a minimum estimate, and if the error associated with $\alpha_{CO}$ is large enough, then the best fit $\alpha_{CO}$ values can be considered as a lower threshold for the system. / Thesis / Master of Science (MSc)

Problem: Primary HSV-2 infection during pregnancy is associated with adverse pregnancy outcomes. However the mechanisms underlying these outcomes remain largely unknown. In this study we developed and characterized a mouse model of primary HSV-2 infection during early pregnancy and examined its effects on pregnancy and fetal outcomes. Methods of Study: C57BL/6 female mice positive for vaginal plugs were infected intravaginally (IVAG) with 10^3/10^4/10^5 PFU/mouse of HSV-2 (333) or saline (control) on gestational day (GD) 5. For comparison, female mice in diestrus stage were infected with HSV-2 at the same doses. Survival, pathology scores and vaginal viral shedding were measured post-infection. Systemic viral dissemination was examined by real-time PCR. Vaginal tissue, implantation sites, placenta and fetuses were examined by histology. Maternal serum (GD 13) and amniotic fluid (GD 8) was collected for multiplex cytokine analysis. Results: The minimum viral inoculation dose for infection in pregnant mice was 10^3 PFU of HSV-2, compared to 100-fold higher dose required to infect diestrus mice (10^5 PFU). There was a dose-dependent increase in implantation failure and number of resorptions with increasing dose of viral inoculum in pregnant mice at GD 8. In the 10^3 PFU group, although vaginal viral shedding was observed in all mice, 75% survived the infection, while all the mice in 10^4 and 10^5 PFU groups succumbed to infection by GD 13-15. There was evidence of abnormal placental morphology and necrotic fetal tissues in HSV-2 infected, pregnant mice compared to controls. Presence of HSV-2 DNA was measured in the vaginal tract, uterus (mated non-pregnant mice), and implantations of infected mated mice. HSV-2 DNA was also present in the spleen of the GD 13 time point group. Conclusions: These results indicate a 100-fold increase in susceptibility to HSV-2 infection during early pregnancy. At higher inoculation doses, IVAG HSV-2 infection spread systemically resulting in poor pregnancy outcomes and maternal mortality, especially in later gestation. At lower inoculation dose, the infection was localized in the reproductive tract and implantation sites, resulting in increased inflammation and adverse outcomes. This model will help to understand pathological mechanisms underlying adverse outcomes following primary HSV-2 infection in pregnancy. / Thesis / Master of Science (MSc)

SARS-CoV-2 wastewater surveillance is a promising tool for monitoring the spread of infection during pandemic outbreaks. 24-hour composite sampling of wastewater using autosamplers is the preferred means for wastewater surveillance sample collection. Autosamplers however require a significant capital cost and furthermore some sampling locations are not amenable to autosampler deployment because of a lack of space and lack of access to electricity. Grab sampling is an alternative to auto sampling for wastewater surveillance, however it may be less effective compared to 24-hour composite sampling due to the possibility to miss the collection of shed disease targets during critical shedding events. Torpedo-style passive samplers packed with medical gauze and tampon-style passive samplers are alternatives to grab sampling when deployment of autosamplers is not possible. Torpedo-style and tampon-style passive samplers are characterized as being easy to deploy and collect and have shown promise for disease surveillance using wastewater. Although passive samplers have shown the ability to detect SARS-CoV-2, they have not demonstrated the ability to quantify the viral load in the wastewater due to the fact that the collection of the liquid phase of the sampler is not consistent across the deployment period of a passive sampler. As SARS-CoV-2 disease targets have been shown to largely partition to the solids phase of wastewaters, it is hypothesized that mass fraction quantitation may enable passive samplers to quantify wastewater signals comparably to autosamplers. In this study, wastewater samples were collected from the same location over a period of three months from a sewer access point at the University of Ottawa using conventional 24-hour auto sampling. Two types of torpedostyle passive samplers and a tampon-style passive sampler were tested to assess whether passive sampler measurements of SARS-CoV-2 N1 and N2 gene targets can be used in the place of autosampler quantitated values. When comparing the wastewater characteristics of centrifuged pellets collected by various passive samplers and a conventional autosampler, the results of this study showed that the torpedo-style passive sampler packed with two pieces of gauze (P2) collected significantly lower water content compared to the autosampler, and P2 collected significantly greater total solids and volatile solids compared to the autosampler. When measuring SARS-CoV-2 N1 and N2 signals, the results indicate that N1 and N2 gene region copy numbers from all of the samplers were not significantly distinct. However, the P2 sampler, a torpedo-style passive sampler packed with four pieces of gauze (P4), and the tampon-style passive sampler (T) captured a greater quantity of pepper mild iii mottle virus (PMMoV) gene targets compared to the autosampler; where PMMoV is the most commonly measured fecal biomarker for wastewater surveillance of SARS-CoV-2. The greater quantity of PMMoV gene targets compared to the autosampler was likely due to proportionally higher total solids and volatile solids in the centrifuged pellet material captured. When N1 and N2 measurements were normalized against sample volume, pellet mass or PMMoV gene copy numbers, P2, P4, and T showed no significant differences compared to the autosampler. In contrast, differences were observed between passive samplers and the autosampler when PMMoV measurements were normalized against the matrix volumes or pellet mass. High statistical percentage differences were observed between all passive samplers and the autosampler. Overall, passive samplers are reliable, cost-effective devices for sampling disease targets in wastewater if results are expressed as copies/g or copies/copies PMMoV. These devices are feasible substitutes for autosamplers when detection and quantification of SARS-CoV-2 in wastewater are required. P2 passive samplers using units of measurement of copies/g are recommended for SARS-CoV-2 surveillance in the wastewater.

SARS-CoV-2 has plagued the world since 2019 with continuously emergence of new variants, resulting in repeated waves of outbreak. Although the countermeasures like vaccination campaign has taken worldwide, the sophisticated virus mutated to escape immune system, threatening the public health. To win the race with the virus and ultimately end the pandemic, we have to take one step ahead to predict how the SARSCoV-2 might evolve and defeat it at the beginning of a new wave. Hence, we proposed a deep learning based framework to first build a deep learning model to shape the fitness landscape of the virus and then use genetic algorithm to predict the high-risk variants that might appear in the future. By combining pre-trained protein language model and structure modeling, the model is trained in a supervised way, predicting the viral transmissibility and antibodies escape ability to eight antibodies simultaneously. The prevenient virus evolution trajectory can be largely recovered by our model with high correlation to their sampling time. Novel mutations predicted by our model show high antibody escape through in silico simulation and overlapped with the mutations developed in prevenient infected patients. Overall, our scheme can provide insights into the evolution of SARS-CoV-2 and hopefully guide the development of vaccination and increase the preparedness.

Background: Respiratory tract infections are responsible for millions of deaths annually. Interferon-stimulated genes (ISGs) play a significant role in fighting off viral respiratory tract infections in the antiviral defence system. Measuring extracellular protein products of ISGs could be potential biomarkers of viral infection. Although, the feasibility and performance of ISGs as functional and robust clinical biomarkers from a non-invasive sample format remains unknown. Methods: Three ISGs, CXCL10, CXCL11, and TNFSF10, were examined in in-vivo and in-vitro gene expression datasets (RNA-sequencing and microarray) infected with common respiratory tract infections (Rhinovirus, Respiratory syncytial virus, influenza A and SARS-CoV-2) samples and compared to negative controls. Using qualitative selection criteria of 1) elevated presence in at least one dataset with viral infection, 2) secreted protein product, and 3) commercially available antibodies for detection, CXCL10, CXCL11 and TNFSF10 gene expression levels were assessed. A correlation analysis was performed with SARS-CoV-2 infection severity and gene expression kinetics. CXCL10 was subsequently validated at the protein level in saliva as a prerequisite for developing a host-response LFA. Results: CXCL10 and CXCL11 upregulation were positively correlated with RSV compared to control (p < 0.05). CXCL10/CXCL11/TNFSF10 were not different between samples collected from RV infected subjects relative to controls (p > 0.05). No significant association was found with influenza A for all three genes. CXCL10/CXCL11/TNFSF10 upregulation was positively correlated with SARS-CoV-2 infection compared to control (p < 0.001). CXCL10 expression correlated with COVID-19 viral load. CXCL10 was chosen as a lead biomarker candidate based on these analyses that included different virus infections, time-courses, and measures of severity. CXCL10 was not detected at the protein level in healthy saliva but was elevated in saliva from COVID-19 patients. A CXCL10 LFA was developed with a sensitivity of 2 ng/ml in a buffer and artificial saliva. Conclusion: We establish and validate the potential of developing rapid test techniques to examine host immune response from a bioinformatic approach to developing a prototype rapid test with capabilities to be used in point-of-care settings. / Thesis / Master of Science (MSc) / Respiratory tract infections are a leading cause of death and one of the main reasons to seek primary care. Both historically and in the present day, respiratory tract infections remain a massive socioeconomic burden. Current diagnostics fail to quickly identify a respiratory tract infection's etiology, and prognosis, leading to suboptimal patient care and the over prescription of antibiotics. Advanced tools used in academia and research, including next-generation -omics sequencing and metagenomics, have capabilities to identify all nucleic acid material in a sample - including host RNA- which offers potential to improve the diagnosing of respiratory tract infections. However, these technologies have not been integrated into routine care due to economic, technical, and logistical barriers. We explored host RNA (transcriptomics), looking at antiviral interferon-stimulated genes for their potential as a biomarker of viral infection amenable to point-of-care testing platforms from non-invasive sample types.

This thesis takes as its subject Paul’s use of sarcasm, using 2 Corinthians 10–13 as a case study. While there has been some work done on the related subject of irony in the Pauline corpus, scholarship has not addressed the issue of sarcasm specifically. For this reason, not only is a dedicated work on sarcasm useful for its own sake, but it also has the potential to nuance previous work on irony, as it can be difficult to generalize when dealing with such a broad rhetorical category. Due to the paucity of previous work on sarcasm – or related subjects – in Paul, the second major contribution of the study will be methodological. The goal of this discussion is to generate a working definition of sarcasm and to develop techniques for sarcasm recognition in ancient texts. To this end, I will survey ancient and modern thought on sarcasm so as to benefit from the insights of contemporary research while grounding the work in categories relevant to a Pauline context. Following the question of method, the final task will be an analysis of 2 Cor 10–13. Here the aim is threefold: to identify and analyze sarcastic statements, to address instances where the presence of sarcasm can contribute to the discussion of exegetical issues, and finally, to draw broader conclusions about the rhetorical effects of Paul’s use of sarcasm. / Thesis / Master of Arts (MA) / This thesis analyzes Paul’s use of sarcasm in 2 Corinthians 10–13. To this end, the first two chapters seek to answer the questions: What is sarcasm? And, how do we find sarcasm in ancient texts far removed from our own culture? We approach these questions by surveying both ancient and modern thought on sarcasm. The goal at this point is to draw as straight a line as possible from classical to contemporary discussions, so that our analysis of Paul can benefit the insights of recent work while remaining grounded in terms current to Paul’s day. With this background, it is then possible to address Paul’s use of sarcasm in 2 Corinthians 10–13. The primary aims of this chapter are to identify sarcastic statements and analyze how they contribute to Paul’s overall argumentation. Additionally, instances where our analysis can contribute to scholarly debates over certain passages are also addressed.