13 research outputs found
Modulation of Cardiac Alternans by Altered Sarcoplasmic Reticulum Calcium Release: A Simulation Study
Background: Cardiac alternans is an important precursor to arrhythmia, facilitating formation of conduction block, and re-entry. Diseased hearts were observed to be particularly vulnerable to alternans, mainly in heart failure or after myocardial infarction. Alternans is typically linked to oscillation of calcium cycling, particularly in the sarcoplasmic reticulum (SR). While the role of SR calcium reuptake in alternans is well established, the role of altered calcium release by ryanodine receptors has not yet been studied extensively. At the same time, there is strong evidence that calcium release is abnormal in heart failure and other heart diseases, suggesting that these changes might play a pro-alternans role.Aims: To demonstrate how changes to intracellular calcium release dynamics and magnitude affect alternans vulnerability.Methods: We used the state-of-the-art Heijman–Rudy and O’Hara–Rudy computer models of ventricular myocyte, given their detailed representation of calcium handling and their previous utility in alternans research. We modified the models to obtain precise control over SR release dynamics and magnitude, allowing for the evaluation of these properties in alternans formation and suppression.Results: Shorter time to peak SR release and shorter release duration decrease alternans vulnerability by improved refilling of releasable calcium within junctional SR; conversely, slow release promotes alternans. Modulating the total amount of calcium released, we show that sufficiently increased calcium release may surprisingly prevent alternans via a mechanism linked to the functional depletion of junctional SR during release. We show that this mechanism underlies differences between “eye-type” and “fork-type” alternans, which were observed in human in vivo and in silico. We also provide a detailed explanation of alternans formation in the given computer models, termed “sarcoplasmic reticulum calcium cycling refractoriness.” The mechanism relies on the steep SR load–release relationship, combined with relatively limited rate of junctional SR refilling.Conclusion: Both altered dynamics and magnitude of SR calcium release modulate alternans vulnerability. In particular, slow dynamics of SR release, such as those observed in heart failure, promote alternans. Therefore, acceleration of intracellular calcium release, e.g., via synchronization of calcium sparks, may inhibit alternans in failing hearts and reduce arrhythmia occurrence
β-Adrenergic Receptor Stimulation and Alternans in the Border Zone of a Healed Infarct: An ex vivo Study and Computational Investigation of Arrhythmogenesis
Background: Following myocardial infarction (MI), the myocardium is prone to calcium-driven alternans, which typically precedes ventricular tachycardia and fibrillation. MI is also associated with remodeling of the sympathetic innervation in the infarct border zone, although how this influences arrhythmogenesis is controversial. We hypothesize that the border zone is most vulnerable to alternans, that β-adrenergic receptor stimulation can suppresses this, and investigate the consequences in terms of arrhythmogenic mechanisms.Methods and Results: Anterior MI was induced in Sprague-Dawley rats (n = 8) and allowed to heal over 2 months. This resulted in scar formation, significant (p < 0.05) dilation of the left ventricle, and reduction in ejection fraction compared to sham operated rats (n = 4) on 7 T cardiac magnetic resonance imaging. Dual voltage/calcium optical mapping of post-MI Langendorff perfused hearts (using RH-237 and Rhod2) demonstrated that the border zone was significantly more prone to alternans than the surrounding myocardium at longer cycle lengths, predisposing to spatially heterogeneous alternans. β-Adrenergic receptor stimulation with norepinephrine (1 μmol/L) attenuated alternans by 60 [52–65]% [interquartile range] and this was reversed with metoprolol (10 μmol/L, p = 0.008). These results could be reproduced by computer modeling of the border zone based on our knowledge of β-adrenergic receptor signaling pathways and their influence on intracellular calcium handling and ion channels. Simulations also demonstrated that β-adrenergic receptor stimulation in this specific region reduced the formation of conduction block and the probability of premature ventricular activation propagation.Conclusion: While high levels of overall cardiac sympathetic drive are a negative prognostic indicator of mortality following MI and during heart failure, β-adrenergic receptor stimulation in the infarct border zone reduced spatially heterogeneous alternans, and prevented conduction block and propagation of extrasystoles. This may help explain recent clinical imaging studies using meta-iodobenzylguanidine (MIBG) and 11C-meta-hydroxyephedrine positron emission tomography (PET) which demonstrate that border zone denervation is strongly associated with a high risk of future arrhythmia
New Zealand Business Environment
The thesis examines business environment of New Zealand. The aim of the thesis is to conduct a situational analysis of the business environment through PESTLE analysis, which is necessary for successful market penetration and elimination of the related business risks. Another goal is to verify the hypothesis, that New Zealand business environment is perspective for Czech economic subjects. Possibilities of Czech subjects to be economically active on the local market will be analysed in the last chapter. The thesis should serve as a complex source of information for Czech businessmen, exporters and investors, who are or intend to be economically active in New Zealand
New Zealand Business Environment
Práce se zabývá specifiky podnikatelského prostředí Nového Zélandu. Jejím cílem je provedení situační analýzy podnikatelského prostředí země prostřednictvím PESTLE analýzy, jež je nezbytným předpokladem úspěšného proniknutí na trh a eliminace podnikatelských rizik s tím spojených. Dále bude ověřena hypotéza, zda je toto prostředí perspektivní pro české ekonomické subjekty, a v závěrečné kapitole práce budou rozebrány možnosti uplatnění českých subjektů na zdejším trhu. Práce by měla sloužit jako komplexní zdroj informací jak pro budoucí, tak i stávající české podnikatele, exportéry a investory směřující svoji ekonomickou činnost na novozélandský trh.The thesis examines business environment of New Zealand. The aim of the thesis is to conduct a situational analysis of the business environment through PESTLE analysis, which is necessary for successful market penetration and elimination of the related business risks. Another goal is to verify the hypothesis, that New Zealand business environment is perspective for Czech economic subjects. Possibilities of Czech subjects to be economically active on the local market will be analysed in the last chapter. The thesis should serve as a complex source of information for Czech businessmen, exporters and investors, who are or intend to be economically active in New Zealand
Systemic thought
This graduation thesis tries to summarize the systemic thouf.(ht, its scientist sources, systemic thought development and general and tbeoretical bases. This NL A. thesis is theoretical/y aimed and its objective is to present a synthesis of the systemic approach .. The systemic approach is a new point oť view in psychology, with its roots in 1950's. The systemic thought is inspired by three basic theoretical sources: general system theory, radical constructivism and social constructionism. The theory of systems is an interdiscip/inary theory that studies properties of systems as a whole. The radical constructivism is an approach to the problem of knowledge and knowing. ft starts from the assumption that knowledge is in the heads of persons, and that the thinking subject has no alternative but to construct what they know on the basis of their own experience. The social constructionism aims to discover the ways in which individuals and groups participate in the creation of their perceived reality. ft involves looking at the ways social phenomena are created, institutionalized, and forged into tradition by humans. The "socially constructed reality" is seen as an ongoing, dynamic process: the reality is reproduced by people acting on their interpretations and their knowledge of it. Furthermore, this thesis..
Business and Cultural Specifics of Burma
The aim of my bachelor thesis is to outline the process of business negotiation in Burma, business etiquette and cultural specifics of the country and also to verify the hypothesis that they are so different from our practices as to prevent citizens of the Czech Republic and Burma from communicating and doing business with each other, or that they distinctively complicate these matters. The paper should serve as a comprehensive guide for future investors, entrepreneurs, business representatives and other people, who want to learn something more about this country. The body of the thesis is divided into four chapters, whereas the introductory chapter provides basic characteristics of the country such as history, geography, demography, administrative division of the country and the current political situation. The second chapter is focused on the economic stuation and business relations between Burma and the Czech Republic with an emphasis on basic conditions of the use of Czech products in the local marketplace. The third chapter is an analysis of business practices and etiquette, and the last chapter concentrates on specific features of Burmese culture, whose knowledge constitutes a basic prerequisite for misunderstanding the nature of the local population and establishment of successful business relations. The paper is based on Czech and foreign books and internet resources, statistics made by international organizations,observations of guide Radka Tkáčiková, personal experience of foreign business representatives operating in Burma and information provided by Ing. Ivan Chválny from the Embassy of the Czech Republic in Bangkok
Manual Re-evaluation of Translation Quality of WMT 2018 English-Czech systems
This data set contains four types of manual annotation of translation quality, focusing on the comparison of human and machine translation quality (aka human-parity). The machine translation system used is English-Czech CUNI Transformer (CUBBITT). The annotations distinguish adequacy, fluency and overall quality. One of the types is Translation Turing test - detecting whether the annotators can distinguish human from machine translation.
All the sentences are taken from the English-Czech test set newstest2018 (WMT2018 News translation shared task www.statmt.org/wmt18/translation-task.html), but only from the half with originally English sentences translated to Czech by a professional agency
Manual Re-evaluation of Translation Quality of WMT 2018 English-Czech systems
This data set contains four types of manual annotation of translation quality, focusing on the comparison of human and machine translation quality (aka human-parity). The machine translation system used is English-Czech CUNI Transformer (CUBBITT). The annotations distinguish adequacy, fluency and overall quality. One of the types is Translation Turing test - detecting whether the annotators can distinguish human from machine translation.
All the sentences are taken from the English-Czech test set newstest2018 (WMT2018 News translation shared task www.statmt.org/wmt18/translation-task.html), but only from the half with originally English sentences translated to Czech by a professional agency
CUBBITT Translation Models (en-fr) (v1.0)
CUBBITT En-Fr translation models, exported via TensorFlow Serving, available in the Lindat translation service (https://lindat.mff.cuni.cz/services/translation/).
Models are compatible with Tensor2tensor version 1.6.6.
For details about the model training (data, model hyper-parameters), please contact the archive maintainer.
Evaluation on newstest2014 (BLEU):
en->fr: 38.2
fr->en: 36.7
(Evaluated using multeval: https://github.com/jhclark/multeval
CUBBITT Translation Models (en-cs) (v1.0)
CUBBITT En-Cs translation models, exported via TensorFlow Serving, available in the Lindat translation service (https://lindat.mff.cuni.cz/services/translation/).
Models are compatible with Tensor2tensor version 1.6.6.
For details about the model training (data, model hyper-parameters), please contact the archive maintainer.
Evaluation on newstest2014 (BLEU):
en->cs: 27.6
cs->en: 34.4
(Evaluated using multeval: https://github.com/jhclark/multeval