7 research outputs found

    Building a discrete-event model

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    Diplomová práce popisuje prostředí tvorby diskrétně událostního modelu. Model klasifikace události, systému vyrozumění a varování na jaderné elektrárně je zpracován v prostředí programu Matlab and Simulink. Tvorba modelu je realizována nástrojem pro tvorbu diskrétně událostních modelů Stateflow. Vytvořený model demonstruje přehledné použití dierarchických stavových automatů pro návrh chování diskrétně událostních modelů.This thesis describes building interface of discrete-event modelling. Model of classification and notification and information system for nuclear power station is built in Matlab and Simulink and its discrete-event modelling tool stateflow. The created model demonstrates a clear use of statecharts for the design of discrete-event models.Ústav systémového inženýrství a informatikyStudentka seznámila s výsledky své diplomové práce na téma Návrh diskrétně událostního modelu. Otázky byly směřovány na oblast návrhu modelu. Autorka na otázky pohotově odpovídala. \nl{}\nl{} Otázky komise: \begin{tecky} \item{} Odpovídá Váš model reálnému stavu v jaderné elektrárně? \item{} V jakém nástroji mají samotní pracovníci jaderné elektrárny modelovány tyto situace? \item{} Na základě jakých podkladů jste vytvořila tento model? \end{tecky

    Compilement of e-learning course for the subject ZIT - part WORD

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    Bakalářská práce se nejprve zabývá pojmy distanční vzdělávání a e-learning. Jsou zde uvedeny silné a slabé stránky distančního vzdělávání, historie a formy e-learningu. Další část práce je zaměřena na LMS systémy využívané v ČR, zejména pak LMS eDoceo a jeho nástroj Autor, který byl použit k tvorbě e-learningového kurzu Základy práce MS Word, kterému je věnována poslední kapitola bakalářské práce.Ústav systémového inženýrství a informatikyDokončená práce s úspěšnou obhajobo

    Na+/K+-ATPase Revisited: On Its Mechanism of Action, Role in Cancer, and Activity Modulation

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    Maintenance of Na+ and K+ gradients across the cell plasma membrane is an essential process for mammalian cell survival. An enzyme responsible for this process, sodium-potassium ATPase (NKA), has been currently extensively studied as a potential anticancer target, especially in lung cancer and glioblastoma. To date, many NKA inhibitors, mainly of natural origin from the family of cardiac steroids (CSs), have been reported and extensively studied. Interestingly, upon CS binding to NKA at nontoxic doses, the role of NKA as a receptor is activated and intracellular signaling is triggered, upon which cancer cell death occurs, which lies in the expression of different NKA isoforms than in healthy cells. Two major CSs, digoxin and digitoxin, originally used for the treatment of cardiac arrhythmias, are also being tested for another indication—cancer. Such drug repositioning has a big advantage in smoother approval processes. Besides this, novel CS derivatives with improved performance are being developed and evaluated in combination therapy. This article deals with the NKA structure, mechanism of action, activity modulation, and its most important inhibitors, some of which could serve not only as a powerful tool to combat cancer, but also help to decipher the so-far poorly understood NKA regulation

    Quo Vadis Advanced Prostate Cancer Therapy? Novel Treatment Perspectives and Possible Future Directions

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    Prostate cancer is a very common disease, which is, unfortunately, often the cause of many male deaths. This is underlined by the fact that the early stages of prostate cancer are often asymptomatic. Therefore, the disease is usually detected and diagnosed at late advanced or even metastasized stages, which are already difficult to treat. Hence, it is important to pursue research and development not only in terms of novel diagnostic methods but also of therapeutic ones, as well as to increase the effectiveness of the treatment by combinational medicinal approach. Therefore, in this review article, we focus on recent approaches and novel potential tools for the treatment of advanced prostate cancer; these include not only androgen deprivation therapy, antiandrogen therapy, photodynamic therapy, photothermal therapy, immunotherapy, multimodal therapy, but also poly(ADP-ribose) polymerase, Akt and cyclin-dependent kinase inhibitors

    BODIPY-based fluorescent liposomes with sesquiterpene lactone trilobolide

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    Like thapsigargin, which is undergoing clinical trials, trilobolide is a natural product with promising anticancer and anti-inflammatory properties. Similar to thapsigargin, it has limited aqueous solubility that strongly reduces its potential medicinal applications. The targeted delivery of hydrophobic drugs can be achieved using liposome-based carriers. Therefore, we designed a traceable liposomal drug delivery system for trilobolide. The fluorescent green-emitting dye BODIPY, cholesterol and trilobolide were used to create construct 6. The liposomes were composed of dipalmitoyl-3-trimethylammoniumpropane and phosphatidylethanolamine. The whole system was characterized by atomic force microscopy, the average size of the liposomes was 150 nm in width and 30 nm in height. We evaluated the biological activity of construct 6 and its liposomal formulation, both of which showed immunomodulatory properties in primary rat macrophages. The uptake and intracellular distribution of construct 6 and its liposomal formulation was monitored by means of live-cell fluorescence microscopy in two cancer cell lines. The encapsulation of construct 6 into the liposomes improved the drug distribution in cancer cells and was followed by cell death. This new liposomal trilobolide derivative not only retains the biological properties of pure trilobolide, but also enhances the bioavailability, and thus has potential for the use in theranostic applications

    Steroid Glycosides Hyrcanoside and Deglucohyrcanoside: On Isolation, Structural Identification, and Anticancer Activity

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    Cardiac glycosides (CGs) represent a group of sundry compounds of natural origin. Most CGs are potent inhibitors of Na+/K+-ATPase, and some are routinely utilized in the treatment of various cardiac conditions. Biological activities of other lesser known CGs have not been fully explored yet. Interestingly, the anticancer potential of some CGs was revealed and thereby, some of these compounds are now being evaluated for drug repositioning. However, high systemic toxicity and low cancer cell selectivity of the clinically used CGs have severely limited their utilization in cancer treatment so far. Therefore, in this study, we have focused on two poorly described CGs: hyrcanoside and deglucohyrcanoside. We elaborated on their isolation, structural identification, and cytotoxicity evaluation in a panel of cancerous and noncancerous cell lines, and on their potential to induce cell cycle arrest in the G2/M phase. The activity of hyrcanoside and deglucohyrcanoside was compared to three other CGs: ouabain, digitoxin, and cymarin. Furthermore, by in silico modeling, interaction of these CGs with Na+/K+-ATPase was also studied. Hopefully, these compounds could serve not only as a research tool for Na+/K+-ATPase inhibition, but also as novel cancer therapeutics
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