• COVID-19
• Other research productsclose
• 2023-2023close
• HU close

In my dissertation, I described two label-free optical biosensors based on integrated optical (IO) structures for the sensitive, rapid detection of pathogens - bacterial cells, viral proteins - from fluid samples, which can serve as a basis for rapid clinical tests. These types of devices provide a specific, cost-effective, user-friendly and portable way of detection with sufficient sensitivity by changing the optical signal. Thus, in practice, they could potentially be used as point-of-care (POC) or home rapid diagnostic tests, offering a promising alternative to traditional laboratory assays. Their realization is supported by their integration with microfluidic channels in a lab-on-a-chip (LOC) device, for handling small volumes of fluid. Based on these aspects, biosensors were designed as waveguides, integrated in a microfluidic channel on a glass substrate, performing evanescent-field sensing. The detection method is based on the fact that the light, propagating in the waveguide with total internal reflections, penetrates into the surrounding media at a limited extent, which is called the evanescent field. Material can enter this space and become bound to the surface, which can change the phase of the light, propagating in the structure, or even scatter it into the surrounding medium. These phenomena offer the possibility of specific detection of pathogens, adhering to the surface, pre-coated with a biological recognition element, such as an antibody. As a first application, an electro-optical biosensor was developed with an evanescent field-based detection concept, aiming at label-free, rapid, selective and sensitive detection of bacteria from body fluids. The usability of the measurement principle, based on the processing of light-scattering patterns, caused by evanescent waves, scattered on target cells, was demonstrated by quantitative detection of Escherichia coli bacterial cells from their suspensions. One of the keys to the applicability of biosensors is their sensitivity. To increase it in case of this device, I applied the phenomenon of dielectrophoresis using the polarizability of the target cells. It provides the possibility to selectively collect cells on the surface of electrodes placed close to the waveguide and then detect them based on the evanescent field. To test this, I wanted to sense bacteria in an artificial urine sample containing somatic cells, in this case endothelial cells, mimicking urine in an inflammatory state. By optimizing the parameters of the measurements, a rapid, sensitive bacterial detection of about 10 minutes was achieved. The detection limit of the biosensor was comparable to the characteristic pathogen concentration in body fluids. Furthermore, selective bacterial detection was also achieved from a fluid sample containing somatic cells, mimicking inflammatory urine. In my dissertation, a second application is also presented, in this case a miniature IO Mach-Zehnder interferometer-based biosensor was developed for the specific quantitative detection of viral proteins. Thanks to the interferometric measurement principle, a fast and accurate detection of target proteins can be achieved. With this device, the aim was to investigate the potential neuroinvasion of coronavirus (SARS-CoV-2) infection, from which point of view the pathological effects of viral surface spike proteins on the blood-brain barrier are of great importance in the case of severe symptoms. Furthermore, infection may also cause adverse effects in the intestinal tract. Thus, the specific aim of this application was to evaluate the ability of the S1 subunit of the coronavirus surface spike protein to cross the human in vitro blood-brain barrier and intestinal epithelial biological barrier system models using the biosensor. Experiments were designed to use the sensor for specific, quantitative detection of spike proteins, that may have been passed through permeability assays on biological barrier models prepared by our collaborators. To reach the specific sensing of the target protein, the waveguide surface of the interferometer’s measuring arm was functionalized with specific S1 protein antibody. To achieve optimal, stable measurement conditions, the operating point of the interferometer was adjusted thermo-optically. The results of the experiments with the biosensor were in agreement with the ones of the conventional immunological tests (ELISA) carried out in parallel. It was possible to determine that S1 protein could pass through the two types of barriers in different amounts. The findings of the experiments with the integrated optical Mach-Zehnder interferometer biosensor demonstrate that this detection approach can be used for similar medical diagnostic purposes, and thus can contribute to the investigation of the adverse effects of SARS-CoV-2 on the human body.

How do the main elements and actors shaping women’s rights at the macro, mezzo and micro levels relate to each other during different periods of crisis, in different circumstances, and how does the traditional division of gender roles influence decision-makers in approaching the question of gender equality? Would a greater inclusion of women in decision-making reinforce democracy building and overwrite the division of gender roles? To answer the research questions a qualitative case-study research design was applied to compare the evolution of women’s rights in Morocco and Tunisia from independence until the present day with a special focus on the post-Arab Spring period and the impacts of the COVID-19 pandemic. Incorporating both inductive and deductive methods and examining the link between a cause or a set of causes and the outcome, process tracing was chosen as the qualitative analysis methodology. In addition to the survey and the evaluation of primary and secondary sources, the dissertation collected data from twenty interviews conducted with women’s rights activists and representatives of different NGOs from Morocco and Tunisia, while also setting up the researcher’s own datasets from the empirical analysis. The new results of the dissertation can be summarised as follows: • Building on a novel methodology the dissertation applies a complex framework that takes into consideration actors, elements and their interactions at the macro (international conventions), mezzo (decision-makers, states) and micro (non-state actors) levels. The conduct of interviews enriched the quality of the research, especially in the context of the pandemic which urged the researcher to apply alternative methods and reach representatives and activists online. In addition, based on previously unseen data interviews helped the researcher to arrive at new results. • Based on the analysis of the functioning of the government and the interviews, the dissertation proves that the absence of responsibility from the leadership leads to general disappointment among local people towards decision-makers. This anarchical situation reinforces the recognition of women’s rights NGOs that in some regions quasi fill the position of the government. • The Arab Spring and the pandemic established a quite favourable environment for civil society to play a more active role and exert pressure on decision-makers. However, the socioeconomic conditions (political turmoil in Tunisia, foreign indebtedness, the increase in the unemployment rate) overwrote initial expectations and did not allow the actors to fully exploit the new opportunities. • The Arab Spring brought about the re-emergence of Islamists, the consequences of which were most apparent from the point of women’s rights in Tunisia where school dropouts significantly increased. • The interviews proved that the evolution of women’s rights in Morocco and Tunisia does not exclusively depend on traditions and cultural norms but on the level of education. Statistical indicators also proved this result which explains why Tunisia has always been ahead of Morocco in terms of the development of women’s rights. • Contrary to the general perception, the interviews proved that the solidarity among women’s rights NGOs is more apparent in the marginalized regions of Morocco and Tunisia.

This PhD thesis presents three new mathematical models aimed at advancing the current understanding of viral dynamics and cancer. The models are implemented in the HAL system and are applied to address current significant questions in the field. The first model, described in Chapter 3, is focused on the evolution of sensitive and resistant tumor cells and considers Darwinian selection, Lamarckian induction, and microvesicle transfer as mechanisms for resistance. The model is compared to an agent-based model and provides insight into the impact of microvesicles on the spread of cancer cells. Chapter 4 presents a hybrid partial differential equation - agent-based (PDE-ABM) model to describe the spatiotemporal viral dynamics in a cell population. The virus concentration is modeled as a continuous variable, while changes in the states of cells are represented by a stochastic agent-based model. The two subsystems are intertwined and the model is applied to predict SARS-CoV-2 and influenza infections. The results are compared to a classical ODE system of viral dynamics and demonstrate the importance of considering spatial patterns in predicting the spread of infections. In Chapter 6, the pharmacometric features of the novel antiviral drug Paxlovid for SARS-CoV-2 are explored using a hybrid multiscale mathematical approach. The results of the evaluation match clinical expectations and provide insight into the importance of early interventions and the sensitivity of the results to the diffusion coefficient of the virus. Overall, this PhD thesis makes a significant contribution to the current understanding of viral dynamics and cancer and demonstrates the potential of mathematical models to provide insight into these complex systems.

Colquitt–Zapata-Phelan (2007) munkássága alapján elmondható, hogy a kutatásom eredménye magas elméleti hozzájárulást jelent a turisztikai szakirodalom területén, továbbá megfelelőképpen illeszkedik a hazai és nemzetközi turisztikai szakirodalom aktuális fejlődéséhez. A doktori értekezés új tudományos eredményei a következő pontokban ismertetem: • Gasztronómiai turizmus elméletének szintetizálása és mélyítése különböző aspektusokból úgy, mint a definíciós csoportosítás, a kutatási fókuszpontok perspektívái és a diszciplináris kontextus. • Influencer témakör szakirodalomban történő elhelyezése, amelyet az e-WOM szakirodalmából indítok el és vezetek végig a fogyasztói döntéshozatal folyamatáig, amelyből következetesen építem fel a harmadik elemet a fogyasztói aktivitást. Az influencer témakört tekintve a legkiemelkedőbb rész maga az influencer jelenség definiálása, továbbá az influencerek követőikre gyakorolt hatásának mechanizmusa, amelynek a kulcsa a vizualizáció. Még az e-WOM és az online vélemények kapcsán több magyar nyelvű kutatási is ismert, addig influencer témakörben kevés kutatás lelhető fel a nemzetközi szakirodalomhoz viszonyítva. • Fogyasztói aktivitás vizsgálata során a fogyasztók közösségi média aktivitására fókuszálok. Az elemzés során olyan modelleket ismertetek, amelyek hozzájárulnak a fogyasztói aktivitás irodalmának részletes elemzéséhez. • Ajzen (1991) tervezett magatartási modelljének kibővítése az aktivitással, illetve moderátorok (desztináció és Covid-19) alkalmazása a fogyasztási szándék és valós fogyasztás kapcsolatának tanulmányozása során, amely által egy új elméleti koncepciót teszteltem a PLS-SEM módszerrel. • A modellen belül a gasztronómiai influencerek és a gasztronómiai fogyasztási szándék közötti kapcsolatot is vizsgálom, amely a turisztikai kutatások területén újszerű megközelítés. • A skálafejlesztés folyamata a magyar szakirodalomban szintén jelentőséggel bír, habár a látens változók mérésénél alkalmazott skálákat már korábban más, nemzetközi publikációk során alkalmazták (mely alátámasztja a megbízhatósági és érvényességi kritériumot), azok újszerűségét a témakörre történő adaptálásuk jelenti. • A PLS-SEM modellezés alkalmazása a turisztikai kutatások területén a hazai szakirodalom tekintetében jelentős, mivel a 2016-2020 között időszakban mindösszesen öt turisztikai jellegű szakcikk született ezen módszer alkalmazásával (KEMÉNY 2021). • A PLS-SEM modell elemzés egyik kiemelkedő eleme a Q2 érték, amely a modell prediktivitását jelenti. A kapott értékek tehát a 0,633 (fogyasztási szándék) és a 0,676 (valós fogyasztás és utazás) azt jelölik, hogy a modell magas prediktív relevanciát mutat. Az elméletből kiindult hipotéziseket empirikus módszerrel tesztelt összefüggések legtöbbje igazolást nyert, így azok tudományos szignifikanciája erősödött. Még a megcáfolt összefüggések is hasznos következtetésekhez vezettek, további kutatási lehetőségek vizsgálatát előjelezve. A téma tudományos újszerűségét továbbá emeli az interdiszciplináris nézőpont a társadalomtudományok területén a turizmusmarketing oldaláról, illetve a szociálpszichológia pszichológiai megközelítésből. A kutatás elsődleges célja volt egyrészt a gasztronómiai indíttatású fogyasztási szándék többoldalú, komplex folyamatának és az összefüggések feltárása. Másrészt a szakemberek és a kutatók is nehezen tudják mérni az influencerek hatását a fogyasztókra, ezért a kutatás lehetőséget nyújt a fogyasztók viselkedésének és lehetséges viselkedésük végkimenetelének megismerésére. Tehát jelen kutatás empirikus eredményei az általános marketing és menedzsment területeken is felhasználhatók.

The extended application area of capnography was verified in a bench test study and clinical investigation. The in vitro study involving artificial lungs with different mechanical properties gave insight into the eneven ventilation distribution driven by the markedly altered resistive and/or elastic properties of the individual sides. These findings contributed to a better understanding of ventilation heterogeneities in a lung, including compartments with different time constants. Due to the high reproduction number of SARS-CoV-2 virus, there may be a sudden increase in the number of patients requiring mechanical ventilation. This can lead to an acute shortage of ventilators in critical care. Using capnogaphy in Study I., we demonstrated that the adequacy of ventilator splitting can be verified. However, ventilator splitting can only be considered as a rescue intervention to provide adequate tidal volumes without collateral airflow for two subjects with different respiratory systems. Our experimental results support that this split ventilation modality can be applied without the risk of diminishing patient safety if emergencies arise due to temporal shortages of mechanical ventilators. Therefore, the risk of non-ventilation is higher than that of controlled shared ventilation in terms of morbidity. Moreover, goal-oriented capnography can serve as a bedside approach to ensure the adequacy of tidal volumes on both lungs during this life saving intervention. Capnography as a routinely available monitoring modality may help in emergencies (i.e. in pandemics or combat hospitals) when there is a lack of equipment and/or health care professionals. From this aspect, ventilator sharing can be regarded as a lifesaving manoeuvre in catastrophe medicine. This alternative may have importance during the exacerbation of an upcoming epidemic wave, or devastating war-related tragic events when intensive care specialists may be faced with a shortage of ventilators. Study II. demonstrated that, diabetes affects airway function and the elastic properties of the respiratory tissues, leading to ventilation heterogeneities. This inhomogenous alveolar emptying was confirmed by capnography showing an elevated phase III slope. These intrinsic mechanical and ventilation abnormalities in diabetes were counterbalanced by the increased contractile response of the pulmonary vasculature to hypoxic stimuli, which was able to maintain the normal intrapulmonary shunt fraction and oxygenation ability of the lungs. On the other hand, obesity similarly deteriorated the global respiratory mechanics, and the external trigger worsened gas exchange. The simultaneous presence of diabetes and obesity had additive effects on the worsened respiratory resistance. This synergistic effect may be related to the combination of the external mechanical overload exerted by the upward shift of the diaphragm in obesity, and the enhanced susceptibility of the alveoli to collapse subsequent to type II pneumocyte dysfunction in the presence of diabetes secretion. These pathophysiological changes highlight the importance of lung protective ventilation with high PEEP and low VTs not only in obesity, but also in patients with diabetes. Taking together the findings of the two studies may have clinical relevance. Since a high proportion of the critically ill COVID-19 patients are diabetic and/or obese, detailed information obtained by capnography may help to optimize mechanical ventilation in the case of a necessity for shared ventilation in a population overwhelmed by diabetic and/or obese patients.