Major accidents in the process industries occurred mostly as an outcome of multiple failures in different safety barriers and their interrelation with unsafe acts by frontline operators. This has become the reason why safety analyses in terms of plant technical aspects cannot be performed independently from analysing human response to the changing technology. Unsafe acts and errors by operators must be seen as a symptom of system insufficiencies and underlying problems, rather than as the cause of an accident. With this paradigm, the need to optimally configure the system and the whole working condition to understand human’s limitation and requirements becomes very evident. It is too naive to desire that human operators make zero error by asking them to change their behaviour and to perfectly adapt to the system. Human Factors (HF) attempts to cope with the need to understand the interrelation between human operators, the technology they are working with and the management system, with the aim to increase safety and efficiency. In achieving this goal, HF must be incorporated into the whole plant lifecycle, from the earliest design stage to plant operation and modifications. Moreover, HF analysis must comprise all kinds of operators’ activities and responsibilities in operating process plants, which can include manual works in field and supervisory control conducted remotely from a control centre/room. This work has developed techniques that provide systematic way to incorporate HF into process plant lifecycle. The new HF analysis technique, PITOPA-Design, in a combination with the classic PITOPA, is applicable for an implementation during design and operation of a plant. With the awareness that safety analysis and HF cannot be performed separately, an interconnection with HAZOPs is made possible by means of this new technique. Moreover, to provide a systematic analysis of operators’ work in control room, an additional technique, the PITOPA-CR was also developed. This HF technique can as well be integrated into a general HF analysis both during design phase and plant operation. In addition to it, results coming from PITOPA-CR will provide information required to optimally configure control and alarm system, as well as the whole alarm management system to better understand the limitation and requirements of control room operators. The structure of the development can be described as follows: i) Development of HAZOPA (the Hazards and Operator Actions Analysis), which provides the interconnection between HF analysis and HAZOPs, ii) Development of PITOPA-Design, a technique to incorporate HF consideration into design phase, which is differentiated into 3 stages to comprise the conceptual design, the basic engineering and the detail engineering phase, iii) Development of PITOPA-CR, a technique for HF analysis in control room, iv) Integration of PITOPA-CR into alarm management system, development of a technique for alarm prioritization. / Schwere Unfälle in der Prozessindustrie erfolgen meist aus einem Zusammenspiel mehrerer verschiedener Fehler und der gleichzeitigen Wechselwirkung mit falschem menschlichem Handeln. Dabei sind diese Fehlhandlungen nicht als Unfallursache anzusehen, sondern sie resultieren aus Fehlern, die in dem System selbst zu finden sind. Aus diesem Grund kann bei der Sicherheitsanalyse die technische Analyse nicht unabhängig von der Betrachtung des Human Factors (HF) durchgeführt werden. Um eine Reduzierung der Fehlhandlungen zu erreichen, müssen das Anlagendesign, die Bedienbarkeit und die Arbeitsumgebung an die menschlichen Fähigkeiten angepasst werden. Human Factors (HF) betrachtet die Interaktion zwischen menschlichen, technischen und organisatorischen Aspekten einer Anlage, mit dem Ziel die Sicherheit und Effektivität der Anlage zu optimieren. Dafür ist eine Einbindung von HF in den gesamten Lebenszyklus einer Anlage notwendig. So müssen HF- Analysen nicht nur während des Betriebs einer Anlage und bei Prozessmodifikationen durchgeführt werden, sondern auch während des gesamten Design- Prozesses, da gerade in den frühen Design-Phasen das Optimierungspotential besonders hoch ist. Eine solche Analysemethode muss alle Aufgaben eines Operators erfassen, so dass zwischen manueller Arbeit und der Arbeit in der Leitwarte unterschieden werden muss. In dieser Arbeit wurden Analysentechniken entwickelt, die einen systematischen Ansatz zur Berücksichtigung des HF über den gesamten Lebenszyklus einer verfahrenstechnischen Anlage darstellen. Mit Hilfe der neuen Analysemethode, PITOPA-Design, können Untersuchungen sowohl während der Designphase als auch während des Betriebs einer Anlage durchgeführt werden. Da solche HF-Analyse immer in Verbindung mit einer klassischen Sicherheitsanalyse erfolgen muss, bindet die neue Methode die HAZOP-Analyse direkt ein. Darüber hinaus wurde ein weiterer Ansatz für die Analyse von Operatorhandlungen in einer Messwartenarbeit entwickelt. Diese neue Analysentechnik, PITOPA-CR, bildet die Grundlage für Verbesserungen im Alarmsystem und wird in das Alarmmanagementsystem eingebunden. Die Arbeit ist wie folgt strukturiert: i) Entwicklung von HAZOPA (the Hazards and Operator Actions Analysis). Diese Methode stellt die Einbindung der HF-Analyse in HAZOP dar. ii) Entwicklung von PITOPA-Design, zur HF-Analyse während des gesamten Designprozesses einer verfahrenstechnischen Anlage. Die Methode wurde in 3 Teile eingeteilt, um die drei Designsphasen Conceptual-, Basic-, und Detail-Design zu erfassen. iii) Entwicklung von PITOPA-CR, zur HF-Analyse in der Messwarte. iv) Einbindung von PITOPA-CR in das Alarmmanagementsystem und Entwicklung einer Technik zur Alarmpriorisierung.

The thesis deals with the issue of thermal-technical assessment of new building of family house which is going to be built in the near future, based on provided documentation. Considering the building system, it is a wooden house, which is going to be realized through a "balloon frame" method. The goal of this thesis is to propose suitable composition of individual constructions, to asses them and to develop basic construction details of them which will be evaluated based on internal surface temperature and linear thermal transmission. Based on intermediate results the thermal loss of the family house will be calculated which is a crucial input for proposal of the heating system. Another part focuses on proposing of controlled ventilation system and creating energy performance certificates of the building.

Cardiovascular pharmaceuticals are among the most prescribed drugs. As a result of the high consumption, these pharmaceuticals have been frequently detected in waste and surface waters. Verapamil, diltiazem and atenolol are very important representatives of cardiovascular pharmaceuticals; therefore, the present research focused on their acute and sub-chronic effects, bioconcentration, half-life time and metabolism in fish. Moreover, unified protocol for the quantitative assessment of histopathological alterations on the heart ventricle and coronary blood vessels employing heart index calculation was developed with the aim to better assess histopathological changes in fish heart which is one of the targets of cardiovascular pharmaceuticals and other chemicals. The effects caused by high concentrations of the studied substances, verapamil, diltiazem and atenolol, in fish can be considered similar to the therapeutic effects and side effects that are found in humans. The acute exposure to verapamil at the human therapeutic plasma level reduced the heart rate in common carp embryos and larvae. In addition, the acute and chronic exposure to this substance caused peripheral edema and gastrointestinal haemorrhage in carp. Similarly, the histological changes in heart and the blood vessels of the liver in diltiazem exposed rainbow trout suggested vasodilatation similar to the pharmacological effect of diltiazem in the human body. In rainbow trout sub-chronically exposed to atenolol at a human therapeutic blood plasma concentration, histopathological changes in the cardiovascular system were found. The bioconcentration of verapamil, diltiazem and atenolol in fish can be classified as low. Bioconcentration factor (BCF) of verapamil in whole body homogenates of common carp ranged between 6.6 and 16.6. The BCF of diltiazem was also relatively low (0.5-194) in analysed tissues of trout, following the order kidney liver muscle blood plasma. BCF of atenolol in rainbow trout tissues was the lowest among the tested substances (BCF = 0.002-0.27), following the order of liver > kidney > muscle. In the blood plasma, the concentration of atenolol was below the limit of quantification. Verapamil showed a longer half-life time (10.6 days) in fish compared to the human body, indicating the slow rate of biotransformation and/or elimination of verapamil in fish. Estimated half-life times of diltiazem in liver (1.5 h) and kidney (6.2 h) were in the same order of magnitudes as those determined for the human blood plasma. The half-life time of atenolol in trout was not studied, because of its very low bioconcentration. In diltiazem exposed rainbow trout, 8 groups of metabolites of diltiazem with 17 different isoforms were identified using liquid chromatography/high resolution mass spectrometry method. Diltiazem was found to undergo a biotransformation involving desmethylation, desacethylation and hydroxylation in fish. These results showed that diltiazem was metabolised in fish in a similar way like in the human body by desmethylation and desacethylation. On the other hand, hydroxylation, which was involved to a minor extent, seemed to be species specific. Verapamil had no effect on early life stages of common carp at the environmentally relevant concentration after one month lasting exposure. On the other hand, atenolol and diltiazem in environmentally realistic concentrations caused after 42-day exposure some physiological changes in rainbow trout. Namely, atenolol affected haematological and biochemical parameters of the blood in exposed rainbow trout and diltiazem caused changes in the activity of antioxidant enzymes in trout liver and gills. These data indicated that atenolol and diltiazem, when present in the aquatic environment, could be a source of sub-lethal detrimental effects in fish.

This thesis deals with the solution of differential equations of the first degree. The work is intended to serve as a textbook (a collection of exercises) for students of teaching mathematics at lower secondary schools. Each chapter contains a summary of basic concepts, solved task models of the related topic, sorted by difficulty, and finally tasks assigned for independent practicing. This thesis aims to present basic knowledge about ways of solving differential equations of the first degree, including practical skills for their solution.

This Thesis drala with the topic of smoking and alkohol use among students JU. The meaning of the work lies in trying to figure out what is the relationship and dependence in combination. The aim of the thesis is to explore the situation of smoking and dribling among students JU. Find out what students occupy a positron on these negative lifestyle factors, what are the relationships between smoking and dribling alkohol, or dependence on them and on the basis of analyzes to compare the results relationships, addiction, and the numer od students JU.

Background: Uterine fibriod (UF) or leiomyoma is the most frequent benign tumour upon lower genital tract and represents the most frequent indication for hysterectomy. The aetiology remains still unknown. The genetic factors contributing for the development of UF are being intensively investigated. The aim of our study was to look for possible genetic markers which could be used as prognostic tools for evaluation of an increased risk for development of UF. Methods: The study group enrolled 102 patients diagnosed with UF and 145 healthy controls. Ultrasonographic examination of the pelvis was performed and a single blood sample was taken in all women. Histological verification followed the surgery in the patient group. The principal of the cytokine gene polymorphisms detection is based on PCR reaction with sequence-specific primers. Results: A large spectrum of Th1/Th2 cytokine gene polymorphisms in patients with uterine fibroid was compared with control group. The frequencies of the majority of tested cytokine gene SNP in the patient cohort were not statistically different from the cytokine SNP in the control group. However, an intriguing association between polymorphisms of the IL-4 gene promotor at positions -590 C/T and -33 C/T, and the risk of leiomyoma was observed. The CC genotype of IL-4 at position...

The pathogenesis of insulin resistance is a complex and still intensively studied issue. Endocrine and paracrine activity of the adipose tissue together with mi- tochondrial dysfunction are the most discussed potential factors included in the development of insulin resistance. In the first part of our study we examined the involvement of the adipose tissue and its secretory products in the etiopathogenesis of insulin resistance in patients with Cushing's syndrome, acromegaly and simple obesity. We focused on three important regulators of metabolic homeostasis - fibroblast growth factors 21 and 19 (FGF-21 and FGF-19) and adipocyte fatty acid binding protein (FABP-4). We found significantly elevated circulating levels of FGF-21 and FABP-4 ac- companying insulin resistance in both patients with simple obesity and patients with obesity connected to Cushing's syndrome, as compared to healthy controls. The concentrations of both substances were comparable between hypercortisolic and obese patients. This finding together with the absence of correlation be- tween the levels of FGF-21 resp. FABP-4 and cortisol suggest that the reason for elevation of their concentrations is obesity and its metabolic consequences themselves rather then the effect of hypercortisolism on FGF-21 and FABP-4 production. We found no...

Pathogenesis of mucopolysaccharidosis type IIIC (MPS IIIC) and Gaucher disease has not been yet fully clarified, and the causes of phenotypical variability between the patients with the same genotype in Gaucher disease remain obscure. Because the variants in the regulatory regions of genes can cause phenotypical differences mentioned above, I have studied promoter regions of HGSNAT and GBA genes mutated in these lysosomal disorders. I have shown that there is an alternative promoter of GBA (P2). Additional studies were aimed to elucidate possible physiological functions of P2, and its possible role in the pathogenesis of Gaucher disease. I have found that P2 is not tissue specific, and that its variants do not influence the variability of phenotype in Gaucher patients with the same genotype. P2 is used differentially neither during the differentiation of monocytes to macrophages nor in macrophages from controls and Gaucher patients, in whom there is a prominent storage only in cells of macrophage origin. We have thus not found any changes that would suggest a role for P2 in the pathogenesis of Gaucher disease. I have characterized the promoter region of HGSNAT and shown that the binding of Sp1 transcription factor is important for its expression. Sequence variants found in HGSNAT promoter in...

(AJ) Adipose tissue produces numerous adipokines, pro- and antiinflammatory cytokines and hormones which may influence the development of insulin resistance, type 2 diabetes mellitus and other comorbidities of the metabolic syndrome. The ability of adipose tissue to store lipids and thus protect other organs and tissues from ectopic lipid accumulation and development of insulin resistance (IR) is largely dependent on the adipogenic potential of preadipocytes. The amount and function of these cells may be the key factor in creating "healthy" adipose tissue or on the contrary "unhealthy" adipose tissue eventually leading to metabolic derangements. The regulation of the amount of body fat by converting preadipocytes into mature adipocytes may be crucial in the prevention and treatment of obesity and its comorbidities. One of the reasons for development of insulin resistance can be the inhibition of the differentiation process of preadipocytes into mature adipocytes with consequent ectopic lipid accumulation caused by the secretion of preadipocyte factor - 1 (Pref - 1). Pref - 1 has been discovered recently as a protein produced by preadipocytes but not by mature adipocytes. Pref - 1 is a member of the protein family sharing similarity with epidermal growth factors which regulate the differentiation of...

Kaposi's sarcoma-associated herpesvirus (KSHV) is a DNA tumor virus that has been associated with all epidemiological forms of Kaposi's sarcoma, primary effusion lymphoma (PEL) and multicentric Castleman disease (MCD). Like other herpesviruses, KSHV undergoes two phases of life cycle (latent and lytic replication). During latency, the viral genome persists as a circular episome in the nucleus of the host cell and only a few viral genes are expressed, namely LANA (latency- associated nuclear antigen), Kaposin, vFLIP (viral FLICE inhibitory protein), vCyclin, and vIRF3/LANA2 (viral interferon regulatory factor 3). These viral genes are responsible for regulation of host cell proliferation, prevention of apoptosis, facilitation of immune evasion, and maintenance of the extrachromosomal viral genome during cell divisions. vIRF3 is a multifunctional nuclear protein that is constitutively expressed in KSHV positive PEL cells and Castleman's disease tumors, which expression causes dramatic changes of critical host pathways that are involved in the regulation of apoptosis, cell cycle, antiviral immunity, and tumorigenesis. In our study, we have demonstrated and elucidated predicted mechanism, by which vIRF3 enhances transcription activity of c-Myc. Moreover, we have clarified the previously unappreciated...