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Using genetically modified Leishmania extracellular vesicles as a new treatment against miltefosine resistanceAdrià-Verdeny, Max 06 1900 (has links)
La leishmaniose est une maladie zoonotique vectorielle, causée par le parasite protozoaire
Leishmania, affectant des millions de personnes dans le monde. Il n'existe pas de vaccin pour la
forme humaine, et les médicaments actuels, y compris la miltéfosine (MF), rencontrent une
résistance croissante. Des découvertes récentes montrent que les vésicules extracellulaires (VEs)
de Leishmania contribuent à la propagation des gènes de résistance aux médicaments in vitro. Il
est donc crucial d'explorer de nouvelles méthodes pour lutter contre cette résistance,
notamment à la MF.
Nous avons étudié la capacité de Leishmania génétiquement sensibilisée, par la surexpression du
complexe de transport d'internalisation de la MF (MT-Ros3), à produire des VEs et à moduler la
sensibilité du parasite après un contact in vitro. La co-inoculation de parasites et de VEs de
différentes souches a été évaluée à travers quatre approches différentes. Les analyses
physiologique, protéomique et génomique des VEs ont caractérisé leur profil et guidé
l'interprétation de la sensibilité aux médicaments.
Les résultats montrent que les VEs sensibilisent la souche résistante (Li MF200.5) à la MF après
un contact in vitro, surtout lorsqu'elles sont produites et transférées physiologiquement via la
méthode Membrane semi-perméable. Ainsi, lorsque les VEs sont pré-incubées avec la MF
pendant 3 jours, la sensibilité au médicament augmente significativement. Nous démontrons,
pour la première fois, le rôle de "cheval de Troie" des VEs dans la réduction de la résistance à la
MF, ouvrant ainsi la voie à de nouvelles stratégies pour combattre la résistance aux médicaments
chez Leishmania et d'autres microorganismes. / Leishmaniasis is a vector-borne zoonotic disease caused by the protozoan parasite Leishmania,
affecting millions of people worldwide. There is no vaccine for the human form, and current
drugs, including miltefosine (MF), are facing increasing resistance. Recent discoveries show that
Leishmania extracellular vesicles (EVs) contribute to the spread of drug resistance genes in vitro.
Therefore, it is crucial to explore new methods to combat this resistance, particularly to MF.
We studied the ability of genetically sensitized Leishmania, through the overexpression of the MF
internalization transport complex (MT-Ros3), to produce EVs and modulate the parasite's
sensitivity after in vitro contact. The co-inoculation of parasites and EVs from different strains was
evaluated through four different approaches. Physiological, proteomic, and genomic analyses of
the EVs characterized their profile and guided the interpretation of drug sensitivity.
The results show that EVs sensitize the resistant strain (Li MF200.5) to MF after in vitro contact,
especially when they are produced and transferred physiologically via the Transwell method, a
method involving the passage of EVs through a semi-permeable membrane. Additionally, when
EVs are pre-incubated with MF for 3 days, sensitivity to the drug significantly increases. For the
first time, we demonstrate the "Trojan horse" role of EVs in reducing MF resistance, thus paving
the way for new strategies to combat drug resistance in Leishmania and other microorganisms.
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Vývoj tlumočnických dovedností / Interpreting skills developmentRambousková, Hana January 2016 (has links)
The present thesis addresses the issue of the impact of two independent variables - speech rate and interpreters' experience - on the length of time lag in simultaneous interpreting from English to Czech. Time lag, or ear-voice-span (EVS), in simultaneous interpreting is the time difference between the input in source language and the output in target language. The study comprises of two parts. The first, theoretical part summarises the current state of research on the subject. The second, empirical part compares the average EVS in excerpts of sixty simultaneous interpreting renditions uttered by forty-nine subjects divided into two speech rate categories and three experiential categories. The aim is to find out, firstly, whether there are any differences in EVS length based on speech rate, and, secondly, how the interpreters' level of experience influences their EVS length. The first main finding is that a higher speech rate leads, on average, to a shorter EVS than an optimal speech rate; this does not, however, apply in the case of professional interpreters - their EVS length is not affected by speech rate. The second main finding is that the interpreters' level of experience influences EVS length significantly: the more experienced the subjects, the shorter their EVS on average. While evaluating...
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Evaluating the potential of truck electrification and its implementation from user and agency perspectivesTheodora Konstantinou (5930705) 27 July 2022 (has links)
<p> </p>
<p>The trucking industry seems to be resistant to electrification, even though truck electrification can lead to large societal as well as user benefits. This dissertation develops a framework to inform policy making and enhance electric vehicle (EV) preparedness in the trucking industry through the study of two interrelated elements: (a) the adoption of electric trucks and (b) the appropriate implementation of electric truck technology. These two elements cover the user perspective, which is not adequately studied, and the agency perspective, which is pivotal in the decision-making process. Specifically, this study addressed the following research questions: (i) which factors affect the purchase decisions of truck fleet managers or owners for electric trucks? (ii) what is the ranking of and interrelationships between the barriers to the adoption of electric trucks? (iii) which location criteria should be considered for the strategic implementation of dynamic wireless charging (DWC) in a freight transportation network and where should this technology be located based on these criteria, and (iv) what is the impact of electric truck adoption on highway revenue and potential of alternative funding mechanisms to recover the revenue loss?</p>
<p>For the adoption of electric trucks, a stated preference survey was designed and distributed online to truck fleet managers/owners in the U.S., gathering 200 completed responses. Statistical and multi-criteria decision-making approaches were employed to identify the factors that affect the purchase intentions of truck fleet managers and explore the barriers to electric truck adoption. The results showed that the purchase intentions of truck fleet managers are affected by trucking firm and truck fleet characteristics, behavioral factors/opinions regarding electric trucks, and awareness of innovative charging technologies. Furthermore, electric truck adoption would be accelerated if stakeholders focused on the barriers related to the business model, product availability, and charging time. Additionally, electric truck adopters and non-adopters may not be viewed as one homogenous group, since differences were found in the ranking and interrelationships of barriers to electric truck adoption between these two groups. </p>
<p>The implementation of electric truck technology was examined based on the truck fleet managers’ survey, secondary data sources and the case of Indiana, U.S. A multi-criteria decision-making spatial approach was proposed to identify the candidate locations for the deployment of DWC. It was concluded that the most suitable locations for DWC lanes were on interstates, near airports and ports and away from EV charging stations. A data-driven framework was also developed to quantify the impact of electric truck adoption and estimate the optimal fee for each truck to recover the revenue loss. Using the market penetration levels estimated based on the survey data collected, the average annual fuel tax revenue loss for Indiana was approximately $349M. To maintain the same tax revenue per vehicle, annual fees ranging from $969 (in 2021) to $1,243 (in 2035) for single-unit trucks and $6,192 to $7,321 for combination trucks would be needed. To address public relations problems of EV fee implementation, this study also discussed alternative mitigation measures: a vehicle-miles-traveled fee and a pay-as-you-charge fee.</p>
<p>In summary, this dissertation contributes to the body of literature by providing significant insights regarding the perspectives of truck fleet managers for electric trucks as well as a comprehensive list of all the location criteria for DWC. The proposed frameworks and study findings can be used by policymakers and other major stakeholders of the EV ecosystem to frame certain strategies to accelerate electric truck adoption, identify the most suitable locations for charging infrastructure, better understand the impact of electric trucks on the highway revenue, and provide the groundwork for developing EV roadmaps.</p>
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Electric Road Systems : A feasibility study investigating a possible future of road transportation / Elektriska vägsystem : Genomförbarhetsstudie kring en möjlig framtid för vägstransportSingh, Archit January 2016 (has links)
The transportation sector is a vital part of today’s society and accounts for 20 % of our global total energy consumption. It is also one of the most greenhouse gas emission intensive sectors as almost 95 % of its energy originates from petroleum-based fuels. Due to the possible harmful nature of greenhouse gases, there is a need for a transition to more sustainable transportation alternatives. A possible alternative to the conventional petroleum-based road transportation is implementation of Electric Road Systems (ERS) in combination with electric vehicles (EVs). ERS are systems that enable dynamic power transfer to the EV's from the roads they are driving on. Consequently, by utilizing ERS in combination with EVs, both the cost and weight of the EV-batteries can be kept to a minimum and the requirement for stops for recharging can also be eliminated. This system further enables heavy vehicles to utilize battery solutions. There are currently in principal three proven ERS technologies, namely, conductive power transfer through overhead lines, conductive power transfer from rails in the road and inductive power transfer through the road. The aim of this report is to evaluate and compare the potential of a full-scale implementation of these ERS technologies on a global and local (Sweden) level from predominantly, an economic and environmental perspective. Furthermore, the thesis also aims to explore how an expansion of ERS might look like until the year 2050 in Sweden using different scenarios. To answer these questions two main models (global and Swedish perspective) with accompanying submodels were produced in Excel. The findings show that not all countries are viable for ERS from an economic standpoint, however, a large number of countries in the world do have good prospects for ERS implementation. Findings further indicated that small and/or developed countries are best suited for ERS implementation. From an economic and environmental perspective the conductive road was found to be the most attractive ERS technology followed by overhead conductive and inductive road ERS technologies. The expansion model developed demonstrates that a fast expansion and implementation of an ERS-based transportation sector is the best approach from an economical perspective where the conductive road technology results in largest cost savings until 2050. / Transportsektorn är en viktig del av dagens samhälle och står för 20% av den totala globala energiförbrukningen. Det är också en av de sektorer med mest växthusgasutsläpp, där nästan 95% av energin härstammar från petroleumbaserade bränslen. På grund av växthusgasers potentiellt skadliga karaktär finns det ett behov för en övergång till mer hållbara transportmedel. En möjlig alternativ till den konventionella petroleumbaserade vägtransporten är implementering av elektriska vägsystem (ERS) i kombination med elfordon. Elektriska vägsystem är system som möjliggör dynamisk kraftöverföring till fordon från vägarna de kör på. Sålunda kan man genom att använda ERS i kombination med elbilar, minimera både kostnaden och vikten av batterierna samt även minska eller eliminera antalet stopp för omladdningar. Dessutom möjliggör detta system att även tunga fordon kan använda sig av batterilösningar. Det finns för närvarande i princip tre beprövade ERS-tekniker, nämligen konduktiv kraftöverföring genom luftledningar, konduktiv kraftöverföring från räls i vägen och induktiv kraftöverföring genom vägen. Syftet med denna rapport är att utvärdera och jämföra potentialen för en fullskalig implementering av dessa ERS-teknik på en global och lokal (Sverige) nivå från, framförallt, ett ekonomiskt- och ekologiskt perspektiv. Rapporten syftar också till att undersöka, med hjälp av olika scenarier, hur en utbyggnad av ERS i Sverige skulle kunna se ut fram till år 2050. För att besvara dessa frågor producerades två huvudmodeller (global och lokal perspektiv) med kompletterande undermodeller i Excel. De erhållna resultaten visar att ERS inte är lönsamt ur ett ekonomisk perspektiv i precis alla de undersökta länder, dock har ett stort antal länder i världen visat sig ha goda förutsättningar för ERS. Vidare visar resultaten att små och/eller utvecklade länder är bäst lämpade för ERS. Ur ett ekonomiskt- och ekologiskt perspektiv har konduktiv kraftöverföring från räls i väg tekniken visat sig vara den mest attraktiva, följt av konduktiv kraftöverföring genom luftledningar och induktiv kraftöverföring genom väg teknikerna. Expansionsmodellen som utvecklats visar att en snabb expansion och implementation av en ERS-baserad vägtransportsektor är det bästa alternativet, där tekniken för konduktiv kraftöverföring från räls i väg ger de största kostnadsbesparingar fram till 2050.
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