Search results for: Michal Prochazka

Authors: Dana R. Thomson, Catherine Linard, Sabine Vanhuysse, Jessica E. Steele, Michal Shimoni, Jose Siri, Waleska Caiaffa, Megumi Rosenberg, Eleonore Wolff, Tais Grippa, Stefanos Georganos, Helen Elsey

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The Sustainable Development Goals (SDGs) and Urban Health Equity Assessment and Response Tool (Urban HEART) identify dozens of key indicators to help local decision-makers prioritize and track inequalities in health outcomes. However, presentations and discussions at the International Conference on Urban Health (ICUH) 2017 suggested that additional indicators are needed to make decisions and policies. A local decision-maker may realize that malaria or road accidents are a top priority. However, s/he needs additional health determinant indicators, for example about standing water or traffic, to address the priority and reduce inequalities. Health determinants reflect the physical and social environments that influence health outcomes often at community- and societal-levels and include such indicators as access to quality health facilities, access to safe parks, traffic density, location of slum areas, air pollution, social exclusion, and social networks. Indicator identification and disaggregation are necessarily constrained by available datasets – typically collected about households and individuals in surveys, censuses, and administrative records. Continued advancements in earth observation, data storage, computing and mobile technologies mean that new sources of health determinants indicators derived from 'big data' are becoming available at fine geographic scale. Big data includes high-resolution satellite imagery and aggregated, anonymized mobile phone data. While big data are themselves not representative of the population (e.g., satellite images depict the physical environment), they can provide information about population density, wealth, mobility, and social environments with tremendous detail and accuracy when combined with population-representative survey, census, administrative and health system data. The aim of this paper is to (1) flag to data scientists important indicators needed by health decision-makers at the city and sub-city scale - ideally free and publicly available, and (2) summarize for local decision-makers new datasets that can be generated from big data, with layperson descriptions of difficulties in generating them. We include SDGs and Urban HEART indicators, as well as indicators mentioned by decision-makers attending ICUH 2017.

Keywords: health determinant, health outcome, mobile phone, remote sensing, satellite imagery, SDG, urban HEART

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Authors: Lena Lapidot, Amir Amnon, Rita Nosenko, Veitsman Ella, Cohen-Ezra Oranit, Davidov Yana, Segev Shlomo, Koren Omry, Safran Michal, Ben-Ari Ziv

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Introduction: Hepatocellular carcinoma (HCC) is one of the leading causes of cancer related mortality worldwide. Liver Cirrhosis is the main predisposing risk factor for the development of HCC. The factor(s) influencing disease progression from Cirrhosis to HCC remain unknown. Gut microbiota has recently emerged as a major player in different liver diseases, however its association with HCC is still a mystery. Moreover, there might be an important association between the gut microbiota, nutrition, life style and the progression of Cirrhosis and HCC. The aim of our study was to characterize the gut microbial signature in association with life style and nutrition of patients with Cirrhosis, HCC-Cirrhosis and healthy controls. Design: Stool samples were collected from 95 individuals (30 patients with HCC, 38 patients with Cirrhosis and 27 age, gender and BMI-matched healthy volunteers). All participants answered lifestyle and Food Frequency Questionnaires. 16S rRNA sequencing of fecal DNA was performed (MiSeq Illumina). Results: There was a significant decrease in alpha diversity in patients with Cirrhosis (qvalue=0.033) and in patients with HCC-Cirrhosis (qvalue=0.032) compared to healthy controls. The microbiota of patients with HCC-cirrhosis compared to patients with Cirrhosis, was characterized by a significant overrepresentation of Clostridium (pvalue=0.024) and CF231 (pvalue=0.010) and lower expression of Alphaproteobacteria (pvalue=0.039) and Verrucomicrobia (pvalue=0.036) in several taxonomic levels: Verrucomicrobiae, Verrucomicrobiales, Verrucomicrobiaceae and the genus Akkermansia (pvalue=0.039). Furthermore, we performed an analysis of predicted metabolic pathways (Kegg level 2) that resulted in a significant decrease in the diversity of metabolic pathways in patients with HCC-Cirrhosis (qvalue=0.015) compared to controls, one of which was amino acid metabolism. Furthermore, investigating the life style and nutrition habits of patients with HCC-Cirrhosis, we found significant correlations between intake of artificial sweeteners and Verrucomicrobia (qvalue=0.12), High sugar intake and Synergistetes (qvalue=0.021) and High BMI and the pathogen Campylobacter (qvalue=0.066). Furthermore, overweight in patients with HCC-Cirrhosis modified bacterial diversity (qvalue=0.023) and composition (qvalue=0.033). Conclusions: To the best of the our knowledge, we present the first report of the gut microbial composition in patients with HCC-Cirrhosis, compared with Cirrhotic patients and healthy controls. We have demonstrated in our study that there are significant differences in the gut microbiome of patients with HCC-cirrhosis compared to Cirrhotic patients and healthy controls. Our findings are even more pronounced because the significantly increased bacteria Clostridium and CF231 in HCC-Cirrhosis weren't influenced by diet and lifestyle, implying this change is due to the development of HCC. Further studies are needed to confirm these findings and assess causality.

Keywords: Cirrhosis, Hepatocellular carcinoma, life style, liver disease, microbiome, nutrition

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Authors: Dana Pugach, Michal Tamir

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Most criminal cases end with a plea agreement, an issue whose many aspects have been discussed extensively in legal literature. One important feature, however, has gained little notice, and that is crime victims’ place in plea agreements following the federal Crime Victims Rights Act of 2004. This law has provided victims some meaningful and potentially revolutionary rights, including the right to be heard in the proceeding and a right to appeal against a decision made while ignoring the victim’s rights. While victims’ rights literature has always emphasized the importance of such right, references to this provision in the general literature about plea agreements are sparse, if existing at all. Furthermore, there are a few cases only mentioning this right. This article purports to bridge between these two bodies of legal thinking – the vast literature concerning plea agreements and victims’ rights research– by using behavioral economics. The article will, firstly, trace the possible structural reasons for the failure of this right to be materialized. Relevant incentives of all actors involved will be identified as well as their inherent consequential processes that lead to the victims’ rights malfunction. Secondly, the article will use nudge theory in order to suggest solutions that will enhance incentives for the repeat players in the system (prosecution, judges, defense attorneys) and lead to the strengthening of weaker group’s interests – the crime victims. Behavioral psychology literature recognizes that the framework in which an individual confronts a decision can significantly influence his decision. Richard Thaler and Cass Sunstein developed the idea of ‘choice architecture’ - ‘the context in which people make decisions’ - which can be manipulated to make particular decisions more likely. Choice architectures can be changed by adjusting ‘nudges,’ influential factors that help shape human behavior, without negating their free choice. The nudges require decision makers to make choices instead of providing a familiar default option. In accordance with this theory, we suggest a rule, whereby a judge should inquire the victim’s view prior to accepting the plea. This suggestion leaves the judge’s discretion intact; while at the same time nudges her not to go directly to the default decision, i.e. automatically accepting the plea. Creating nudges that force actors to make choices is particularly significant when an actor intends to deviate from routine behaviors but experiences significant time constraints, as in the case of judges and plea bargains. The article finally recognizes some far reaching possible results of the suggestion. These include meaningful changes to the earlier stages of criminal process even before reaching court, in line with the current criticism of the plea agreements machinery.

Keywords: plea agreements, victims' rights, nudge theory, criminal justice

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Authors: Miroslav Mrlik, Marketa Ilcikova, Martin Cvek, Josef Osicka, Michal Sedlacik, Vladimir Pavlinek, Jaroslav Mosnacek

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Magnetorheological elastomers (MREs) are a unique type of materials consisting of two components, magnetic filler, and elastomeric matrix. Their properties can be tailored upon application of an external magnetic field strength. In this case, the change of the viscoelastic properties (viscoelastic moduli, complex viscosity) are influenced by two crucial factors. The first one is magnetic performance of the particles and the second one is off-state stiffness of the elastomeric matrix. The former factor strongly depends on the intended applications; however general rule is that higher magnetic performance of the particles provides higher MR performance of the MRE. Since magnetic particles possess low stability properties against temperature and acidic environment, several methods how to improve these drawbacks have been developed. In the most cases, the preparation of the core-shell structures was employed as a suitable method for preservation of the magnetic particles against thermal and chemical oxidations. However, if the shell material is not single-layer substance, but polymer material, the magnetic performance is significantly suppressed, due to the in situ polymerization technique, when it is very difficult to control the polymerization rate and the polymer shell is too thick. The second factor is the off-state stiffness of the elastomeric matrix. Since the MR effectivity is calculated as the relative value of the elastic modulus upon magnetic field application divided by elastic modulus in the absence of the external field, also the tuneability of the cross-linking reaction is highly desired. Therefore, this study is focused on the controllable modification of magnetic particles using a novel monomeric system based on 2-(1H-pyrrol-1-yl)ethyl methacrylate. In this case, the short polymer chains of different chain lengths and low polydispersity index will be prepared, and thus tailorable stability properties can be achieved. Since the relatively thin polymer chains will be grafted on the surface of magnetic particles, their magnetic performance will be affected only slightly. Furthermore, also the cross-linking density will be affected, due to the presence of the short polymer chains. From the application point of view, such MREs can be utilized for, magneto-resistors, piezoresistors or pressure sensors especially, when the conducting shell on the magnetic particles will be created. Therefore, the selection of the pyrrole-based monomer is very crucial and controllably thin layer of conducting polymer can be prepared. Finally, such composite particle consisting of magnetic core and conducting shell dispersed in elastomeric matrix can find also the utilization in shielding application of electromagnetic waves.

Keywords: atom transfer radical polymerization, core-shell, particle modification, electromagnetic waves shielding

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Authors: Piotr Tylec, Alicja Dudek, Grzegorz Torbicz, Magdalena Mizera, Natalia Gajewska, Michael Su, Tanawat Vongsurbchart, Tomasz Stefura, Magdalena Pisarska, Mateusz Rubinkiewicz, Piotr Malczak, Piotr Major, Michal Pedziwiatr

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Introduction: Quality of life after bariatric surgery is an important factor when evaluating the final result of the treatment. Considering the vast surgical options, we tried to globally compare available methods in terms of quality of following the surgery. The aim of the study is to compare the quality of life a year after bariatric intervention using network meta-analysis methods. Material and Methods: We performed a systematic review according to PRISMA guidelines with Bayesian network meta-analysis. Inclusion criteria were: studies comparing at least two methods of weight loss treatment of which at least one is surgical, assessment of the quality of life one year after surgery by validated questionnaires. Primary outcomes were quality of life one year after bariatric procedure. The following aspects of quality of life were analyzed: physical, emotional, general health, vitality, role physical, social, mental, and bodily pain. All questionnaires were standardized and pooled to a single scale. Lifestyle intervention was considered as a referenced point. Results: An initial reference search yielded 5636 articles. 18 studies were evaluated. In comparison of total score of quality of life, we observed that laparoscopic sleeve gastrectomy (LSG) (median (M): 3.606, Credible Interval 97.5% (CrI): 1.039; 6.191), laparoscopic Roux en-Y gastric by-pass (LRYGB) (M: 4.973, CrI: 2.627; 7.317) and open Roux en-Y gastric by-pass (RYGB) (M: 9.735, CrI: 6.708; 12.760) had better results than other bariatric intervention in relation to lifestyle interventions. In the analysis of the physical aspects of quality of life, we notice better results in LSG (M: 3.348, CrI: 0.548; 6.147) and in LRYGB procedure (M: 5.070, CrI: 2.896; 7.208) than control intervention, and worst results in open RYGB (M: -9.212, CrI: -11.610; -6.844). Analyzing emotional aspects, we found better results than control intervention in LSG, in LRYGB, in open RYGB, and laparoscopic gastric plication. In general health better results were in LSG (M: 9.144, CrI: 4.704; 13.470), in LRYGB (M: 6.451, CrI: 10.240; 13.830) and in single-anastomosis gastric by-pass (M: 8.671, CrI: 1.986; 15.310), and worst results in open RYGB (M: -4.048, CrI: -7.984; -0.305). In social and vital aspects of quality of life, better results were observed in LSG and LRYGB than control intervention. We did not find any differences between bariatric interventions in physical role, mental and bodily aspects of quality of life. Conclusion: The network meta-analysis revealed that better quality of life in total score one year after bariatric interventions were after LSG, LRYGB, open RYGB. In physical and general health aspects worst quality of life was in open RYGB procedure. Other interventions did not significantly affect the quality of life after a year compared to dietary intervention.

Keywords: bariatric surgery, network meta-analysis, quality of life, one year follow-up

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Authors: Michal Lysek, Mike Danilovic, Jasmine Lihua Liu

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HMS Industrial Networks AB has been recognized as one of the most innovative companies in the industrial communication industry worldwide. The creation of their Anybus innovation during the 1990s contributed considerably to the company’s success. From inception, HMS’ employees were innovating for the purpose of creating new business (the creation phase). After the Anybus innovation, they began the process of internationalization (the commercialization phase), which in turn led them to concentrate on cost reduction, product quality, delivery precision, operational efficiency, and increasing growth (the growth phase). As a result of this transformation, performing new radical innovations have become more complicated. The purpose of our research was to explore the dynamics of innovation at HMS from the aspect of key actors, activities, and events, over the three phases, in order to understand what led to the creation of their Anybus innovation, and why it has become increasingly challenging for HMS to create new radical innovations for the future. Our research methodology was based on a longitudinal, retrospective study from the inception of HMS in 1988 to 2014, a single case study inspired by the grounded theory approach. We conducted 47 interviews and collected 1 024 historical documents for our research. Our analysis has revealed that HMS’ success in creating the Anybus, and developing a successful business around the innovation, was based on three main capabilities – cultivating customer relations on different managerial and organizational levels, inspiring business relations, and balancing complementary human assets for the purpose of business creation. The success of HMS has turned the management’s attention away from past activities of key actors, of their behavior, and how they influenced and stimulated the creation of radical innovations. Nowadays, they are rhetorically focusing on creativity and innovation. All the while, their real actions put emphasis on growth, cost reduction, product quality, delivery precision, operational efficiency, and moneymaking. In the process of becoming an international company, HMS gradually refocused. In so doing they became profitable and successful, but they also forgot what made them innovative in the first place. Fortunately, HMS’ management has come to realize that this is the case and they are now in search of recapturing innovation once again. Our analysis indicates that HMS’ management is facing several barriers to innovation related path dependency and other lock-in phenomena. HMS’ management has been captured, trapped in their mindset and actions, by the success of the past. But now their future has to be secured, and they have come to realize that moneymaking is not everything. In recent years, HMS’ management have begun to search for innovation once more, in order to recapture their past capabilities for creating radical innovations. In order to unlock their managerial perceptions of customer needs and their counter-innovation driven activities and events, to utilize the full potential of their employees and capture the innovation opportunity for the future.

Keywords: barriers to innovation, dynamics of innovation, in search of excellence and innovation, radical innovation

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Authors: Tamir Michal

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The subject of Bedouin dispersion has accompanied the State of Israel from the day of its establishment. From a legal point of view, this subject has offered a launchpad for creative judicial decisions. Thus, for example, the first court decision in Israel to recognize affirmative action (Avitan), dealt with a petition submitted by a Jew appealing the refusal of the State to recognize the Petitioner’s entitlement to the long-term lease of a plot designated for Bedouins. The Supreme Court dismissed the petition, holding that there existed a public interest in assisting Bedouin to establish permanent urban settlements, an interest which justifies giving them preference by selling them plots at subsidized prices. In another case (The Forum for Coexistence in the Negev) the Supreme Court extended equitable relief for the purpose of constructing a bridge, even though the construction infringed the Law, in order to allow the children of dispersed Bedouin to reach school. Against this background, the recent verdict, delivered during the Protective Edge military campaign, which dismissed a petition aimed at forcing the State to spread out Protective Structures in Bedouin villages in the Negev against the risk of being hit from missiles launched from Gaza (Abu Afash) is disappointing. Even if, in arguendo, no selective discrimination was involved in the State’s decision not to provide such protection, the decision, and its affirmation by the Court, is problematic when examined through the prism of the Theory of Recognition. The article analyses the issue by tools of theory of Recognition, according to which people develop their identities through mutual relations of recognition in different fields. In the social context, the path to recognition is cognitive respect, which is provided by means of legal rights. By seeing other participants in Society as bearers of rights and obligations, the individual develops an understanding of his legal condition as reflected in the attitude to others. Consequently, even if the Court’s decision may be justified on strict legal grounds, the fact that Jewish settlements were protected during the military operation, whereas Bedouin villages were not, is a setback in the struggle to make the Bedouin citizens with equal rights in Israeli society. As the Court held, ‘Beyond their protective function, the Migunit [Protective Structures] may make a moral and psychological contribution that should not be undervalued’. This contribution is one that the Bedouin did not receive in the Abu Afash verdict. The basic thesis is that the Court’s verdict analyzed above clearly demonstrates that the reliance on classical liberal instruments (e.g., equality) cannot secure full appreciation of all aspects of Bedouin life, and hence it can in fact prejudice them. Therefore, elements of the recognition theory should be added, in order to find the channel for cognitive dignity, thereby advancing the Bedouins’ ability to perceive themselves as equal human beings in the Israeli society.

Keywords: bedouin dispersion, cognitive respect, recognition theory, sustainable development

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Authors: Anna Lower, Michal Lower, Robert Masztalski, Agnieszka Szumilas

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Contemporary cities are facing serious congestion and parking problems. In urban transport policy the introduction of the park and ride system (P&R) is an increasingly popular way of limiting vehicular traffic. The determining of P&R facilities location is a key aspect of the system. Criteria for assessing the quality of the selected location are formulated generally and descriptively. The research outsourced to specialists are expensive and time consuming. The most focus is on the examination of a few selected places. The practice has shown that the choice of the location of these sites in a intuitive way without a detailed analysis of all the circumstances, often gives negative results. Then the existing facilities are not used as expected. Methods of location as a research topic are also widely taken in the scientific literature. Built mathematical models often do not bring the problem comprehensively, e.g. assuming that the city is linear, developed along one important communications corridor. The paper presents a new method where the expert knowledge is applied to fuzzy inference model. With such a built system even a less experienced person could benefit from it, e.g. urban planners, officials. The analysis result is obtained in a very short time, so a large number of the proposed location can also be verified in a short time. The proposed method is intended for testing of car parks location in a city. The paper will show selected examples of locations of the P&R facilities in cities planning to introduce the P&R. The analysis of existing objects will also be shown in the paper and they will be confronted with the opinions of the system users, with particular emphasis on unpopular locations. The research are executed using the fuzzy inference model which was built and described in more detail in the earlier paper of the authors. The results of analyzes are compared to documents of P&R facilities location outsourced by the city and opinions of existing facilities users expressed on social networking sites. The research of existing facilities were conducted by means of the fuzzy model. The results are consistent with actual users feedback. The proposed method proves to be good, but does not require the involvement of a large experts team and large financial contributions for complicated research. The method also provides an opportunity to show the alternative location of P&R facilities. The performed studies show that the method has been confirmed. The method can be applied in urban planning of the P&R facilities location in relation to the accompanying functions. Although the results of the method are approximate, they are not worse than results of analysis of employed experts. The advantage of this method is ease of use, which simplifies the professional expert analysis. The ability of analyzing a large number of alternative locations gives a broader view on the problem. It is valuable that the arduous analysis of the team of people can be replaced by the model's calculation. According to the authors, the proposed method is also suitable for implementation on a GIS platform.

Keywords: fuzzy logic inference, park and ride system, P&R facilities, P&R location

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Authors: Michal Pachocki

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This study investigates the effects of mobility in the context of a different environment and work culture through analysing the learners perception of their international work experience. Since this kind of professional training abroad is becoming more popular in Europe, mainly due to the EU funding opportunities, it is of paramount importance to assess its long-term impact on educational and career paths of former students. Moreover, the tracer study aimed at defining what professional, social and intercultural competencies were gained or developed by the interns and to which extent those competences proved to be useful meeting the labor market requirements. Being a populous EU member state which actively modernizes its vocational education system (also with European funds), Poland can serve as an illustrative case study to investigate the above described research problems. However, the examined processes are most certainly universal, wherever mobility is included in the learning process. The target group of this research was the former mobility participants and the study was conducted using quantitative and qualitative methods, such as the online survey with over 2 600 questionnaires completed by the former mobility participants; -individual in-depth interviews (IDIs) with 20 Polish graduates already present in the labour market; - 5 focus group interviews (FGIs) with 60 current students of the Polish vocational schools, who have recently returned from the training abroad. As the adopted methodology included a data triangulation, the collected findings have also been supplemented with data obtained by the desk research (mainly contextual information and statistical summary of mobility implementation). The results of this research – to be presented in full scope within the conference presentation – include the participants’ perception of their work mobility. The vast majority of graduates agrees that such an experience has had a significant impact on their professional careers and claims that they would recommend training abroad to persons who are about to enter the labor market. Moreover, in their view, such form of practical training going beyond formal education provided them with an opportunity to try their hand in the world of work. This allowed them – as they accounted for them – to get acquainted with a work system and context different from the ones experienced in Poland. Although the work mobility becomes an important element of the learning process in the growing number of Polish schools, this study reveals that many sending institutions suffer from a lack of the coherent strategy for planning domestic and foreign training programmes. Nevertheless, the significant number of graduates claims that such a synergy improves the quality of provided training. Despite that, the research proved that the transnational mobilities exert an impact on their future careers and personal development. However, such impact is, in their opinion, dependant on other factors, such as length of the training period, the nature and extent of work, recruitment criteria and the quality of organizational arrangement and mentoring provided to learners. This may indicate the salience of the sending and receiving institutions organizational capacity to deal with mobility.

Keywords: learning mobility, transnational training, vocational education and training graduates, tracer study

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Authors: Michal Geca, Grzegorz Baranski, Ksenia Siadkowska

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The work is a part of the project which aims at developing innovative power and control systems for the high power aircraft piston engine ASz62IR. Developed electronically controlled ignition system will reduce emissions of toxic compounds as a result of lowered fuel consumption, optimized combustion and engine capability of efficient combustion of ecological fuels. The tested unit is an air-cooled four-stroke gasoline engine of 9 cylinders in a radial setup, mechanically charged by a radial compressor powered by the engine crankshaft. The total engine cubic capac-ity is 29.87 dm3, and the compression ratio is 6.4:1. The maximum take-off power is 1000 HP at 2200 rpm. The maximum fuel consumption is 280 kg/h. Engine powers aircrafts: An-2, M-18 „Dromader”, DHC-3 „OTTER”, DC-3 „Dakota”, GAF-125 „HAWK” i Y5. The main problems of the engine includes the imbalanced work of cylinders. The non-uniformity value in each cylinder results in non-uniformity of their work. In radial engine cylinders arrangement causes that the mixture movement that takes place in accordance (lower cylinder) or the opposite (upper cylinders) to the direction of gravity. Preliminary tests confirmed the presence of uneven workflow of individual cylinders. The phenomenon is most intense at low speed. The non-uniformity is visible on the waveform of cylinder pressure. Therefore two studies were conducted to determine the impact of this phenomenon on the engine performance: simulation and real tests. Simplified simulation was conducted on the element of the intake system coated with fuel film. The study shows that there is an effect of gravity on the movement of the fuel film inside the radial engine intake channels. Both in the lower and the upper inlet channels the film flows downwards. It follows from the fact that gravity assists the movement of the film in the lower cylinder channels and prevents the movement in the upper cylinder channels. Real tests on aircraft engine ASz62IR was conducted in transients condition (rapid change of the excess air in each cylinder were performed. Calculations were conducted for mass of fuel reaching the cylinders theoretically and really and on this basis, the factors of fuel evaporation “x” were determined. Therefore a simplified model of the fuel supply to cylinder was adopted. Model includes time constant of the fuel film τ, the number of engine transport cycles of non-evaporating fuel along the intake pipe γ and time between next cycles Δt. The calculation results of identification of the model parameters are presented in the form of radar graphs. The figures shows the averages declines and increases of the injection time and the average values for both types of stroke. These studies shown, that the change of the position of the cylinder will cause changes in the formation of fuel-air mixture and thus changes in the combustion process. Based on the results of the work of simulation and experiments was possible to develop individual algorithms for ignition control. This work has been financed by the Polish National Centre for Research and Development, INNOLOT, under Grant Agreement No. INNOLOT/I/1/NCBR/2013.

Keywords: radial engine, ignition system, non-uniformity, combustion process

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Authors: Zuzana Tatarkova, Ivana Pilchova, Michal Cibulka, Martin Kolisek, Peter Racay, Peter Kaplan

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Introduction: Normal functioning of mitochondria is crucial for cardiac performance. Mitochondria undergo mitophagy and biogenesis, and mitochondrial proteins are subject to extensive post-translational modifications. The state of mitochondrial homeostasis reflects overall cellular fitness and longevity. Perturbed mitochondria produce less ATP, release greater amounts of reactive molecules, and are more prone to apoptosis. Therefore mitochondrial turnover is an integral aspect of quality control in which dysfunctional mitochondria are selectively eliminated through mitophagy. Currently, the progressive deterioration of physiological functions is seen as accumulation of modified/damaged proteins with limiting regenerative ability and disturbance of such affected protein-protein communication throughout aging in myocardial cells. Methodologies: For our study was used immunohistochemistry, biochemical methods: spectrophotometry, western blotting, immunodetection as well as more sophisticated 2D electrophoresis and mass spectrometry for evaluation protein-protein interactions and specific post-translational modification. Results and Discussion: Mitochondrial stress response to reactive species was evaluated as electron transport chain (ETC) complexes, redox-active molecules, and their possible communication. Protein-protein interactions revealed a strong linkage between age and ETC protein subunits. Redox state was strongly affected in senescent mitochondria with shift in favor of more pro-oxidizing condition within cardiomyocytes. Acute myocardial ischemia and ischemia-reperfusion (IR) injury affected ETC complexes I, II and IV with no change in complex III. Ischemia induced decrease in total antioxidant capacity, MnSOD, GSH and catalase activity with recovery in some extent during reperfusion. While MnSOD protein content was higher in IR group, activity returned to 95% of control. Nitric oxide is one of the biological molecules that can out compete MnSOD for superoxide and produce peroxynitrite. This process is faster than dismutation and led to the 10-fold higher production of nitrotyrosine after IR injury in adult with higher protection in senescent ones. 2D protein profiling revealed 140 mitochondrial proteins, 12 of them with significant changes after IR injury and 36 individual nitrotyrosine-modified proteins further identified by mass spectrometry. Linking these two groups, 5 proteins were altered after IR as well as nitrated, but only one showed massive nitration per lowering content of protein after IR injury in adult. Conclusions: Senescent cells have greater proportion of protein content, which might be modulated by several post-translational modifications. If these protein modifications are connected to functional consequences and protein-protein interactions are revealed, link may lead to the solution. Assume all together, dysfunctional proteostasis can play a causative role and restoration of protein homeostasis machinery is protective against aging and possibly age-related disorders. This work was supported by the project VEGA 1/0018/18 and by project 'Competence Center for Research and Development in the field of Diagnostics and Therapy of Oncological diseases', ITMS: 26220220153, co-financed from EU sources.

Keywords: aging heart, mitochondria, proteomics, redox state

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Authors: Michal Kielbik, Izabela Szulc-Kielbik, Anna Brzostek, Jaroslaw Dziadek, Magdalena Klink

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The goal of many research groups in the world is to find new components that are important for survival of mycobacteria in the host cells. Mycobacterium tuberculosis (Mtb) possesses a number of enzymes degrading cholesterol that are considered to be an important factor for its survival and persistence in host macrophages. One of them - cholesterol oxidase (ChoD), although not being essential for cholesterol degradation, is discussed as a virulence compound, however its involvement in macrophages’ response to Mtb is still not sufficiently determined. The recognition of tubercle bacilli antigens by pathogen recognition receptors is crucial for the initiation of the host innate immune response. An important receptor that has been implicated in the recognition and/or uptake of Mtb is Toll-like receptor type 2 (TLR2). Engagement of TLR2 results in the activation and phosphorylation of intracellular signaling proteins including IRAK-1 and -4, TRAF-6, which in turn leads to the activation of target kinases and transcription factors responsible for bactericidal and pro-inflammatory response of macrophages. The aim of these studies was a detailed clarification of the role of Mtb cholesterol oxidase as a virulence factor affecting the TLR2 signaling pathway in human macrophages. As human macrophages the THP-1 differentiated cells were applied. The virulent wild-type Mtb strain (H37Rv), its mutant lacking a functional copy of gene encoding cholesterol oxidase (∆choD), as well as complimented strain (∆choD–choD) were used. We tested the impact of Mtb strains on the expression of TLR2-depended signaling proteins (mRNA level, cytosolic level and phosphorylation status). The cytokine and bactericidal response of THP-1 derived macrophages infected with Mtb strains in relation to TLR2 signaling pathway dependence was also determined. We found that during the 24-hours of infection process the wild-type and complemented Mtb significantly reduced the cytosolic level and phosphorylation status of IRAK-4 and TRAF-6 proteins in macrophages, that was not observed in the case of ΔchoD mutant. Decreasement of TLR2-dependent signaling proteins, induced by wild-type Mtb, was not dependent on the activity of proteasome. Blocking of TLR2 expression, before infection, effectively prevented the induced by wild-type strain reduction of cytosolic level and phosphorylation of IRAK-4. None of the strains affected the surface expression of TLR2. The mRNA level of IRAK-4 and TRAF-6 genes were significantly increased in macrophages 24 hours post-infection with either of tested strains. However, the impact of wild-type Mtb strain on both examined genes was significantly stronger than its ΔchoD mutant. We also found that wild-type strain stimulated macrophages to release high amount of immunosuppressive IL-10, accompanied by low amount of pro-inflammatory IL-8 and bactericidal nitric oxide in comparison to mutant lacking cholesterol oxidase. The influence of wild-type Mtb on this type of macrophages' response strongly dependent on fully active IRAK-1 and IRAK-4 signaling proteins. In conclusion, Mtb using cholesterol oxidase causes the over-activation of TLR2 signaling proteins leading to the reduction of their cytosolic level and activity resulting in the modulation of macrophages response to allow its intracellular survival. Supported by grant: 2014/15/B/NZ6/01565, National Science Center, Poland

Keywords: Mycobacterium tuberculosis, cholesterol oxidase, macrophages, TLR2-dependent signaling pathway

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Authors: Martin Cvek, Miroslav Mrlik, Michal Sedlacik, Tomas Plachy

Abstract:

Magnetorheological elastomers (MREs) are multi-phase composite materials containing micron-sized ferromagnetic particles dispersed in an elastomeric matrix. Their properties such as modulus, damping, magneto-striction, and electrical conductivity can be controlled by an external magnetic field and/or pressure. These features of the MREs are used in the development of damping devices, shock attenuators, artificial muscles, sensors or active elements of electric circuits. However, imperfections on the particle/matrix interfaces result in the lower performance of the MREs when compared with theoretical values. Moreover, magnetic particles are susceptible to corrosion agents such as acid rains or sea humidity. Therefore, the modification of particles is an effective tool for the improvement of MRE performance due to enhanced compatibility between particles and matrix as well as improvements of their thermo-oxidation and chemical stability. In this study, the carbonyl iron (CI) particles were controllably modified with poly(trimethylsilyloxyethyl methacrylate) (PHEMATMS) nano-grafts to develop magnetic core–shell structures exhibiting proper wetting with various elastomeric matrices resulting in improved performance within a frame of rheological, magneto-piezoresistance, pressure-piezoresistance, or radio-absorbing properties. The desired molecular weight of PHEMATMS nano-grafts was precisely tailored using surface-initiated atom transfer radical polymerization (ATRP). The CI particles were firstly functionalized using a 3-aminopropyltriethoxysilane agent, followed by esterification reaction with α-bromoisobutyryl bromide. The ATRP was performed in the anisole medium using ethyl α-bromoisobutyrate as a macroinitiator, N, N´, N´´, N´´-pentamethyldiethylenetriamine as a ligand, and copper bromide as an initiator. To explore the effect PHEMATMS molecular weights on final properties, two variants of core-shell structures with different nano-graft lengths were synthesized, while the reaction kinetics were designed through proper reactant feed ratios and polymerization times. The PHEMATMS nano-grafts were characterized by nuclear magnetic resonance and gel permeation chromatography proving information to their monomer conversions, molecular chain lengths, and low polydispersity indexes (1.28 and 1.35) as the results of the executed ATRP. The successful modifications were confirmed via Fourier transform infrared- and energy-dispersive spectroscopies while expected wavenumber outputs and element presences, respectively, of constituted PHEMATMS nano-grafts, were occurring in the spectra. The surface morphology of bare CI and their PHEMATMS-grafted analogues was further studied by scanning electron microscopy, and the thicknesses of grafted polymeric layers were directly observed by transmission electron microscopy. The contact angles as a measure of particle/matrix compatibility were investigated employing the static sessile drop method. The PHEMATMS nano-grafts enhanced compatibility of hydrophilic CI with low-surface-energy hydrophobic polymer matrix in terms of their wettability and dispersibility in an elastomeric matrix. Thus, the presence of possible defects at the particle/matrix interface is reduced, and higher performance of modified MREs is expected.

Keywords: atom transfer radical polymerization, core-shell, particle modification, wettability

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