Formal computational framework for the study of molecular evolution

Over the past 10 years, multiple executable modelling formalisms for molecular biology have been developed in order to address the growing need for a system-level understanding of complex biological phenomena. An important class of these formalisms are biology-inspired process algebras, which offer-among other desirable properties - an almost complete separation of model specification (syntax) from model dynamics (semantics). In this thesis, the similarity between this separation and the genotype-phenotype duality in evolutionary biology is exploited to develop a process-algebraic approach to the study of evolution of biochemical systems. The main technical contribution of this thesis is the continuous π-calculus (cπ), a novel process algebra based on the classical π-calculus of Milner et. al. Its two defining characteristics are: continuous, compositional, computationally inexpensive semantics, and a exible interaction structure of processes (molecules). Both these features are conductive to evolutionary analysis of biochemical systems by, respectively, enabling many variants of a given model to be evaluated, and facilitating in silico evolution of new functional connections. A further major contribution is a collection of variation operators, syntactic model transformation schemes corresponding to common evolutionary events. When applied to a cπ model of a biochemical system, variation operators produce its evolutionary neighbours, yielding insights into the local fitness landscape and neutral neighbourhood. Two well-known biochemical systems are modelled in this dissertation to validate the developed theory. One is the KaiABC circadian clock in the cyanobacterium S. elongatus, the other is a mitogen-activated protein kinase cascade. In each case we study the system itself as well as its predicted evolutionary variants. Simpler examples, particularly that of a generic enzymatic reaction, are used throughout the thesis to illustrate important concepts as they are introduced

A concept of Differentiated Services architecture supporting military oriented Quality of Service, Journal of Telecommunications and Information Technology, 2003, nr 2

This paper presents a concept of IP Differentiated Services (DiffServ) architecture in conjunction with bandwidth brokerage and policy based network management, all aimed at efficient and flexible provision of the military oriented Quality of Service (M-QoS) features in the Australian Defence (strategic) wide area network and its satellite trunk interconnections with the tactical domain. Typical DiffServ functions are analysed in the paper with regard to their roles in offering M-QoS. Some preliminary simulation results of applying these mechanisms to achieve traffic policing and differentiation for (UDP) video traffic streams, are also presented. Finally, the paper proposes the use of bandwidth brokerage in each DiffServ domain to facilitate automatic Service Level Specification (SLS) arrangements with end-user applications, and policy based network management to support the flexible implementation of bandwidth brokerage

Current views on treatment of the ovarian granulosa-cell tumor

Summary The granulosa-cell tumor ( folliculoma ) is a rare type of ovarian neoplasm, accounting for 5% of all cases [1]. It is the most common type of sex cord-stromal tumors, diagnosed in 70% of cases. The granulosa-cell tumor is a hormone active one, originating from granulosa cells which produce estradiol. Overproduction of estradiol is helpful in the diagnosis of the tumor because of its numerous symptoms. There are two types of folliculoma: juvenile (5%) and adult (95%). The juvenile type is mostly recognized ( 90% ) in FIGO I stage and has a better prognosis. Operation is often a sufficient way of treatment in this group [1]. Tumors in higher stages are more aggressive and must be treated further[ 2]. The adult folliculoma is more aggressive in its nature. Patients with the disease diagnosed in higher stages must be treated by adjuvant radiotherapy or chemotherapy[1]. Recurrence appears often many years after the treatment and has high mortality. Many old ( platinum) and new (taxans) agents are active when used in treatment of this type of tumor. Randomized study must be made to establish standard therapy of granulosa-cell tumor. Currently, the most frequent way of treatment is chemotherapy with BEP (Blemycyna, Etopozyd, Cisplatyna)

A prospective cohort analysis of residential radon and UV exposures and malignant melanoma mortality in the Swiss population.

BACKGROUND Radon is a radioactive noble gas naturally found in the earth crust that can accumulate in buildings. In addition to lung cancer, alpha particles emitted by radon may contribute to the risk of skin cancer. We evaluated the association between residential radon exposure and skin cancer mortality, over a fifteen year period, taking residential ultra-violet (UV) exposure into account. METHODS We included 4.9 million adults from the Swiss National Cohort. Hazard ratios for melanoma mortality were estimated using Cox proportional hazard models (20+ years old; follow-up 2001-2015). Long-term modelled residential radon and ambient UV exposures were assigned at baseline, and included together in the Cox models. With age as a time scale, models were adjusted for calendar time, sex, marital status, education, mother tongue, socioeconomic position, and occupational environment with potential for UV exposure. Age specific hazard ratios were derived. Effect modification, sensitivity analyses and the shape of the exposure response, as well as secondary analysis using other outcome definitions, were investigated. RESULTS During follow-up (average of 13.6 years), 3,979 melanoma deaths were observed. Associations declined with age, with an adjusted hazard ratio per 100 Bq/m3 radon at age 60 of 1.10 (95% CI: 0.99, 1.23). The dose-response showed an approximate linear trend between the minimum and mean radon exposure of 75 Bq/m3. Having outdoor occupation significantly increased the risk of melanoma mortality associated with UV exposure compared to indoor jobs. Analysis restricted to the last five years of follow-up showed similar results compared to the main analysis. Similar associations were found for mortality from melanoma and non-melanoma skin cancer combined. CONCLUSION With double the follow-up time, this study confirmed the previously observed association between residential radon exposure and melanoma and non-melanoma skin cancer mortality in Switzerland. Accumulation of radon indoors is preventable and of public health importance

Technique of endovascular repair of iatrogenic subclavian artery injury following subclavian vein catheterization

The iatrogenic subclavian artery injury is a rare but potentially serious complication of subclavian vein cannulation.The use of endovascular techniques is an alternative to surgical repair especially in patients with concomitantdiseases in whom immediate, potentially large surgery would be associated with a high risk of perioperativecomplications. This article discusses technical aspects of endovascular repair of iatrogenic injury of subclavianartery with implantation of covered stents based on two cases. Author’s experience and data from literaturesuggests that endovascular management including covered stent implantation is safe and effective treatmentand should be considered as a method of choice especially among patients in poor general condition and/ormajor comorbidities

A cohort analysis of residential radon exposure and melanoma incidence in Switzerland.

Radon is a radioactive noble gas found in Earth's crust. It accumulates in buildings, and account for approximately half the ionizing radiation dose received by humans. The skin is considerably exposed to ionizing radiation from radon. We aimed to evaluate the association between residential radon exposure and melanoma and squamous cell carcinoma incidence. The study included 1.3 million adults (20 years and older) from the Swiss National Cohort who were residents of the cantons of Vaud, Neuchâtel, Valais, Geneva, Fribourg, and Ticino at the study baseline (December 04, 2000). Cases of primary tumours of skin (melanoma and squamous cell carcinoma) were identified using data from cantonal cancer registries. Long-term residential radon and ambient solar ultraviolet radiation exposures were assigned to each individual's address at baseline. Cox proportional hazard models with age as time scale, adjusted for canton, socioeconomic position, demographic data available in the census, and outdoor occupation were applied. Total and age specific effects were calculated, in the full population and in non-movers, and potential effect modifiers were tested. In total 4937 incident cases of melanoma occurred during an average 8.9 years of follow-up. Across all ages, no increased risk of malignant melanoma or squamous cell carcinoma incidence in relation to residential radon was found. An association was only observed for melanoma incidence in the youngest age group of 20-29 year olds (1.68 [95% CI: 1.29, 2.19] 100 Bq/m3 radon). This association was mainly in women, and in those with low socio-economic position. Residential radon exposure might be a relevant risk factor for melanoma, especially for young adults. However, the results must be interpreted with caution as this finding is based on a relatively small number of melanoma cases. Accumulation of radon is preventable, and measures to reduce exposure and communicate the risks remain important to convey to the public

Mediators of gender effects on depression among cardiovascular disease patients in Palestine

Among patients suffering from coronary heart disease (CHD) and comorbid depression, women experience a higher burden compared to men. Little is known on the characteristics that differentiate men and women with both diseases and whether these factors mediate gender effects on depression. This study assessed whether women are more likely to suffer from depression and which characteristics mediate gender effects on depression among a cardiac population in Palestine, specifically addressing the role of post-traumatic stress disorder (PTSD).; Using a cross-sectional design, patients consecutively admitted with a CHD to one of the four main hospitals in Nablus, Palestine, were interviewed using a structured questionnaire with validated instruments. Data was also obtained from hospital medical records. Patients were assessed for depression using the Cardiac Depression Scale (CDS). Bivariate analysis was conducted to compare characteristics of women and men with and without depressive symptoms. Mediators (direct and indirect effects) of the association between gender and depression were evaluated using a structural equation model (SEM).; Women were more likely to suffer from severe depression than men (28.7% vs. 18.8%). Female gender was positively associated with higher PTSD symptoms, comorbidities, somatic symptoms and income, and with lower resilience, self-esteem, quality of life, education, prevalence of smoking and physical activity. Structural equation modeling revealed negative indirect effects of gender on depression (CDS score) through resilience, self-esteem and physical activity, whereas positive indirect effects of gender on depression were observed through PTSD, comorbidities, somatic symptoms and smoking. There was no direct effect of gender on depression.; This study found a higher prevalence of severe depression in female patients with cardiac disease compared to male cardiac patients. Our findings provide novel information on mediating factors of the association between gender and depression among cardiac patients, in particular PTSD. The results emphasize the need for further research on potential mediating factors that could account for gender differences in depression and the need to provide support programs for female patients with comorbid CHD and depression to improve their psycho-social well-being