Логистика играет ведущую роль в мировой экономике. В настоящее время в логистике происходит цифровая революция, скорость которой постепенно возрастает. Именно цифровизация является тем фактором, который в логистике открывает новые возможности, включая: ускорение, изменение, перестройку бизнес-моделей, оказание расширенного спектра услуг. Однако скорость изменения такова, что логистика не успевает перестроиться и влечет за собой нарушение цепи поставок. Перебои в логистике приводят к нарушению непрерывности цепи поставок. Цель исследования – внедрение инноваций в бизнес-модель транспортной компании для решения актуальных логистических проблем. / Logistics plays a leading role in the global economy. Currently, the digital revolution is taking great place in logistics, the speed of which is gradually increasing. Digitalization is the factor that opens up new opportunities in logistics, including: acceleration, change, restructuring of business models, and the provision of an expanded range of services. However, the speed of change is such that logistics does not have time to adjust and leads to disruption of the supply chain. Disruptions in logistics lead to disruption of the continuity of the supply chain. The purpose of the research is to introduce innovations in the business model of a transport company to solve relevant logistics problems.

Extracellular Vesicles (EVs) are small membranous particles secreted by the cells. They play an important role in intercellular communication and can transport a variety of biomolecules, including proteins, lipids, and nucleic acids, to target cells. The scientific community recently considered EVs attractive candidates for developing targeted drug delivery systems (DDSs), given their biocompatibility, low immunogenicity, stability in biofluids, and capability to cross biological barriers. Most studies have shown the feasibility of incorporating desired moieties at the EV surface through the genetic modification of EV-producing cells, exploiting the fusion with proteins enriched at the EV membrane. Tetraspanins are transmembrane proteins enriched in EVs, already exploited for EV isolation or tracking upon fusion with fluorescent reporters. CD81 is a well-characterized tetraspanin with ubiquitous protein expression, overexpression tolerance and a limited number of encoded protein isoforms with respect to other EV-associated tetraspanins. Here, I have explored a CD81-based approach for EV targeting. CD81, in full-length or truncated form, was used to guide the expression into EVs of an anti-HER2 moiety, namely the light chains of trastuzumab, within three different constructs, including turbo-GFP (tGFP) as a reporter: CD81-tGFP as master control, CD81-antiHER2-tGFP and CD81delta-antiHER2-tGFP. The first part of the project was dedicated to the characterization of chimeric proteins at cellular and vesicular levels. CD81-based constructs were successfully expressed in HEK239T cells with a preferential enrichment in organelle fractions, underlying the expected involvement in the intracellular vesicular trafficking. Next, chimeric proteins were also found in the derived EVs, with a similar expression trend, corroborated by imaging flow cytometry. Nanoparticle tracking analysis and cryogenic electron microscopy acquisitions confirmed that CD81-fusion proteins boosted EV release without altering the size distribution. Subsequently, I tested the binding capacity of the chimeric proteins to HER2 receptor through orthogonal techniques, such as AlphaLISA and immunoprecipitation. Confocal imaging, also on live cells, confirmed EV internalization into breast cancer cells, depending on the recipient cell type and the presence of HER2 receptor. Moreover, chimeric EVs loaded with doxorubicin were able to mediate a concentration-dependent cytotoxic effect on recipient breast cancer cells. Of note, messenger RNA provided a valuable readout of the in vivo delivery capability of the CD81-engineered EVs, since detected by digital droplet PCR in breast cancer tumour xenografts from mice treated with chimeric EVs. The results presented in this thesis highlighted the feasibility of using CD81 fusion proteins for cell targeting and cargo delivery, ultimately opening new perspectives for the development of EV-based therapeutics.

In this paper we develop a digital twin based on the new One Record linked data standard. This enables short-term workload prediction for the various partners in the air cargo supply chain without the need for multiple data exchange interfaces. To the best of our knowledge, it is the first research on the potential benefits of One Record. The concept of the digital twin allows for an overarching optimization of operations in the air cargo supply chain without the necessity of full transparency between all the partners.

A comparative study is carried out to investigate the most promising route towardsthe lightweight construction of a retractable mast for a sailing cargo vessel.Four design families are developed and compared. The primary criteria forjudgment are the structural mass, strength, and stiffness in relation to a providedbenchmark design. Additional evaluation criteria are the capital costsfor raw materials and manufacturing.The design space includes isotropic materials as well as fiber-reinforced polymer(FRP) solutions and is navigated by employing analytical evaluation methodssupported by finite element analysis (FEA). Restrictions to the designspace are given by a general arrangement of the benchmark design. This includesthe limitation to the ULS loads and the overall mast geometry.A review of relevant Det Norske Veritas (DNV) rules for classification is performedand the guidelines for wind turbine blades and wind-powered units(WPU) are judged most suitable to the design challenge. Relevant design principlesare implemented in the structural analysis.It is concluded that pure metal constructions imply an unreasonably large weightpenalty. Local buckling is found to disqualify FRP single-skin solutions as successfulcandidates. Secondary to that, strength concerns are the major driversfor the structural mass.The report presents two designs that are judged fit for the purpose, one is ahybrid truss structure from high strength low alloy steel (HSLA steel) and carbonfiber-reinforced polymer (CFRP). The second design is a sandwich constructionwith CFRP face sheets, a PVC foam core, and additional stiffeningmembers in steel.

Dieser Artikel beschreibt die Konzeption eines Bemessungsfahrzeugs für Lastenfahrräder anhand der Datenerfassung von 103 Fahrzeugen. Ziel war es, aus einer Vielzahl von Lastenfahrrädern, die im Privatsektor genutzt werden, ein „repräsentatives“ Bemessungsfahrzeug zu erstellen, das für verkehrsplanerische Maßnahmen verwendet werden kann. Dazu wurde eine Datenerhebung anhand von Online-Recherchen sowie der Vermessung von Lastenfahrrädern durchgeführt. Aus dieser Datengrundlage konnten 42 unterschiedliche Lastenfahrrad-Modelle mit vollständigen Daten für die Analyse genutzt werden. Auf Basis dieser Analyse wurde ein Bemessungslastenfahrrad entwickelt, das 2,60 Meter lang ist, einen Radstand von exakt 2 Metern besitzt, 1,20 Meter hoch ist, eine 70 Zentimeter breite Transportbox und einen 89 Zentimeter breiten Lenker aufweist. Die Nutzung des entwickelten Bemessungslastenfahrrads ist in der Verkehrsplanung, beispielsweise zur Dimensionierung der Breiten von Radwegen, Abständen zwischen Pollern und Umlaufsperren oder Parkmöglichkeiten für Lastenfahrräder, schon jetzt nutzbar, sollte aber durch eine Hüllkurvensimulation und eine Ausweitung der Stichprobe ergänzt werden.:1. Einleitung 2. Bemessungsfahrzeuge in der Verkehrsplanung 2.1 Relevanz in der Verkehrsplanung 2.2 Grundlagen von Bemessungsfahrzeugen: vom PKW zum Lastenfahrrad 3. Datengrundlage und Methodik 3.1 Angewandte Methodik zur Entwicklung eines Bemessungslastenfahrrads 3.2 Erstellung der Datengrundlage 4. Ergebnisse der Untersuchung 4.1 Auswertung der Lastenfahrrad-Maße 4.2 Erstellung des 85 %-Bemessungsfahrzeugs 5. Schlussfolgerung Literaturverzeichnis / This paper describes the design of a dimensioning vehicle for cargo bikes based on data collection of 103 vehicles. The goal was to create a dimensioning vehicle from a large number of cargo bikes used in the private sector that can be used for transport planning tasks. To accomplish this, a data collection was conducted using online research as well as measuring cargo bikes. From this database, 42 different cargo bike models with a complete dataset could be used for the analysis. From the analysis, it was possible to develop a dimensioning cargo bike, which is 2.60 meters long, has a wheelbase of exactly 2 meters, is 1.20 meters high, has a 70 centimeter wide transport box and 89-centimeter-wide handlebars. The developed dimensioning cargo bike is already usable in transport planning, for example for dimensioning the widths of bike lanes, distances between bollards and circulation grids, or parking facilities for cargo bikes, but should be supplemented by an envelope curve simulation and an expansion of the sample.:1. Einleitung 2. Bemessungsfahrzeuge in der Verkehrsplanung 2.1 Relevanz in der Verkehrsplanung 2.2 Grundlagen von Bemessungsfahrzeugen: vom PKW zum Lastenfahrrad 3. Datengrundlage und Methodik 3.1 Angewandte Methodik zur Entwicklung eines Bemessungslastenfahrrads 3.2 Erstellung der Datengrundlage 4. Ergebnisse der Untersuchung 4.1 Auswertung der Lastenfahrrad-Maße 4.2 Erstellung des 85 %-Bemessungsfahrzeugs 5. Schlussfolgerung Literaturverzeichnis

L’extraction des cires végétales est fréquemment réalisée en utilisant des solvants tels que l’hexane, le cyclohexane, le méthanol, etc. Ces solvants sont très efficaces pour dissoudre les lipides. Cependant, ils sont aussi inflammables, très volatils et toxiques. Récemment, des recherches ont montré que les fluides cryogéniques peuvent aussi servir à cette fin. Par exemple, l’immersion cyclique des fruits entiers dans l’azote liquide (bleuet, argousier, raisin vert) a permis de diminuer les cires cuticulaires jusqu’à 50%. Le but de ce travail est donc d’étudier l’immersion dans l’azote liquide comme méthode ‘verte’ pour extraire la cire des grains. Du sorgho, du blé et du riz brun ont été immergés dans l’azote liquide en 1 à 3 cycles à différentes durées. L’impact du temps de repos entre les cycles (1-5 minutes à température ambiante) sur le rendement d'extraction a aussi été analysé. La performance d’extraction a été comparée à celle par le n-hexane avec la méthode reflux. La microscopie électronique à balayage (SEM) a permis de visualiser l'effet de l'immersion dans l'azote liquide et dans l’hexane sur la surface des grains. La chromatographie en phase gazeuse couplée à un spectromètre de masse (GC-MS) et à un détecteur à ionisation de flamme (GC-FID) a été utilisée pour la détermination de la composition chimique des extraits obtenus par les deux méthodes. Les résultats ont montré que le rendement d’extraction le plus élevé était de 0.026% (g pds cire/100g pds grain) (riz-11minutes d'extraction), 0.032% (sorgho-4 minutes) et 0.025% (blé-13 minutes). En comparaison, le rendement des cires extraites par le n-hexane (70oC) a été de 0.196% (riz-60 minutes d'extraction), 0.298% (sorgho-45 minutes) et 0.126% (blé-30 minutes). Pour le blé et le riz, une augmentation significative du rendement a été observée pour des temps de repos entre 3 et 5 minutes entre les cycles par rapport à celui de 1 minute. Les résultats de GC-MS et GC-FID nous ont confirmé que de la cire a bien été extraire par l’azote liquide et le n-hexane, dont la composition est similaire dans les deux cas. Ces résultats montrent que la méthode d’extraction par l'azote liquide est réalisable malgré son rendement plus faible que celle par l'n-hexane mais avec un temps d’extraction plus court. L’azote liquide n’est pas toxique et c’est un solvant « vert » qui peut être éliminé du produit très facilement par simple évaporation, sans laisser aucune trace problématique. L'utilisation de l'azote liquide comme solvant d'extraction s'avère une méthode prometteuse pour la séparation des composés cireux des grains. La qualité des céréales traitées par l’azote liquide demeure inchangée donc elle pourra être considérée comme une étape secondaire dans le processus de polissage. / Wax extraction from plants is conventionally carried out by using organic solvents such as n-hexane, cyclohexane and methanol. Although, those solvents are very effective in dissolving lipids, they are flammable, toxic and highly volatile. Recent studies show that cryogenic fluids could also be used for wax extraction. For instance, cyclic immersion of whole fruits (blueberry, seabuckthorn, grapes) in liquid nitrogen has significantly reduced cuticular waxes up to 50%. So, the main aim of this work is to use liquid nitrogen as a “green method” to extract waxes from cereals. Several approaches were used to evaluate the extraction method by liquid nitrogen. Sorghum, wheat and brown rice were treated in liquid nitrogen in 1 to 3 cycles with different time intervals. The impact of rest time between cycles (1-5 minutes at room temperature) on the extraction yield was also reported by weighing waxes. The extraction efficiency of the method was compared to that of n-hexane which was referred as the control one. The surface of the grains treated by liquid nitrogen and n-hexane was visualized by the scanning electron microscopy (SEM). Finally, the gas chromatography coupled to mass spectrometry (GC-MS) and flame ionization detector (GC –FID) was used to determine the composition in the extracts resulted from the two methods. Our results showed that the highest extraction efficiency was 0.026% (g cire/100g grain) (rice - 11 extraction minutes), 0.032% (Sorghum - 4 minutes) and 0.025% (wheat -13 minutes). Compared to the extraction by n-hexane method, its efficiency was 0.196% (rice – 60 extraction minutes), 0.298% (sorghum - 45 minutes) and 0.126% (wheat - 30 minutes). For wheat and rice, a significant increase in yield between 3 and 5 rest minutes with respect to the one of 1 minute was observed. The results of GC-MS and GC –FID confirmed that the waxes were extracted out of the grains by both liquid nitrogen and n- hexane. The wax composition of the extract is similar in both cases. These results conclude that the wax extraction method by liquid nitrogen is feasible despite it extracts waxes less than that of n-hexane, but the method benefits for the shorter extraction time. Liquid nitrogen is not toxic and is a "green" solvent which can be easily removed from the products by spontaneously simple evaporation leading no leftover residues. Therefore, using liquid nitrogen as the extraction solvent might be a promising way for separating waxes from waxy grains. The quality of grain processed by liquid nitrogen remains unchanged, thus it may be considered a sub-step in the milling process.

Cotutelle - Mélanie Dieudé / L’ischémie-reperfusion inhérente à toute transplantation d’organe solide induit l’apoptose des cellules endothéliales. Les cellules endothéliales apoptotiques sécrètent des vésicules extracellulaires apoptotiques de type exosome (ApoExo). L’internalisation des ApoExo par les cellules endothéliales (CE) adjacentes conduit à des changements fonctionnels importants dont le dysfonctionnement endothélial. Cependant, les mécanismes d’internalisation des ApoExo par les CE sont méconnus. Des marqueurs fluorescents spécifiques aux protéines et à l’ARN ont été utilisés afin de marquer spécifiquement les ApoExo et étudier leur internalisation par microscopie confocale et cytométrie de flux. Les ApoExo ont été internalisés par les CE en fonction du temps et de la concentration. L’inhibition des voies classiques d’endocytose à l’aide d’inhibiteurs pharmacologiques et d’interférence par ARN n’a pas réduit les niveaux d’internalisation des ApoExo. Le blocage de la phosphatidylsérine des ApoExo avec l’annexine-V a réduit leur internalisation. L’analyse ultrastructurelle par microscopie électronique des CE a révélé la présence de structures lamellipodes importantes pour la macropinocytose dont l’inhibition a diminué le transfert d’ARN et de protéines dans les CE. L’analyse par RT-qPCR a révélé que l’ARNm PCSK5, le plus enrichi dans les ApoExo, est augmenté dans les CE traitées aux ApoExo. Cette augmentation est abolie avec ApoExo exempts d’ARNm PCSK5. Ces résultats démontrent que les ApoExo sont activement internalisés par macropinocytose dépendante de la phosphatidylsérine, favorisant leur internalisation en augmentant l’activité macropinocytique des CE. Les ApoExo transfèrent ainsi des ARN fonctionnels capables de moduler le protéome des CE. Ces résultats ouvrent de nouvelles portes pour la prévention de l’internalisation des ApoExo, et donc de la dysfonction endothéliale. / Ischemia-reperfusion injury inherent to solid organ transplantation induces endothelial apoptosis, releasing apoptotic exosome-like vesicles (ApoExo) which in turn induce endothelial dysfunction. We showed that ApoExo modulates gene expression, functions, and morphology of endothelial cells (EC) towards endothelial dysfunction. However, the mechanism by which EC internalize ApoExo remains unclear. Fluorescent probes specifically targeting proteins and RNA were used to track ApoExo uptake in EC by flow cytometry and confocal microscopy. Pharmacological inhibitors and gene silencing were used to probe uptake mechanisms. RNA and protein expression were quantified using Taqman RT-qPCR and immunoblot, respectively. Uptake of ApoExo by EC was observed in a time- and concentration-dependent manner. Inhibition of clathrin- and caveolae-dependent endocytosis did not decrease ApoExo internalization by EC. Blocking phosphatidylserine on ApoExo surface with annexin-V decreased ApoExo uptake. Ultrastructural analysis of serum-starved EC via electron microscopy revealed lamellipodia-like structures, hallmark of macropinocytosis, whose number increased following ApoExo exposure. Inhibition of macropinocytosis abrogated both RNA and protein transfers from ApoExo to EC. The most enriched mRNA in ApoExo, coding for PCSK5, showed enhanced levels in ApoExo-treated EC along with increased PCSK5 protein levels. This was abrogated by both macropinocytosis inhibition and depletion of PCSK5 mRNA in ApoExo. These results demonstrate that EC actively internalize ApoExo through phosphatidylserine-dependent macropinocytosis, and moreover, that ApoExo further increase macropinocytosis. These findings also show that functional RNAs can be delivered to EC through ApoExo. These results open new avenues for preventing ApoExo internalization and counteracting the development of endothelial dysfunction.

Актуальность темы исследования: обусловлена потребностью в оптимизации процесса транспортировки длинномерных грузов мостовыми кранами с двумя тележками, в повышении точности позиционирования длинномерного груза в месте его назначения с помощью мостового крана с двумя тележками и во введении системы управления с самостоятельным устранением перекоса длинномерного груза. Цель работы: разработка систем управления двухтележечными мостовыми кранами, предназначенных для точного транспортирования длинномерных грузов с возможностью самостоятельного регулирования и устранения перекоса груза. Провести анализ факторов, влияющих на точность перемещения длинномерного груза и представить меры по их учёту в процессе транспортирования груза. В ходе работы были рассмотрены существующие способы согласования работы двух и более кранов, разработаны системы управления двухтележечным мостовым краном с возможностью самостоятельного устранения перекоса груза, представлены факторы, влияющие на точность позиционирования груза и предложены способы учёта некоторых факторов при перемещении груза в место назначения, а также разработаны системы управления тележками и лебёдками двухтележечного мостового крана, учитывающие величину прогиба металлоконструкции крана и растяжения грузового каната при задании величины вертикального перемещения груза. В процессе работы над магистерской диссертацией была оформлена приоритетная заявка на патент на изобретение №2019109823 от 03.04.19г «Двухтележечный мостовой кран» (система представлена в пункте 2.2 данной работы). Также отправлены две заявки на государственную регистрацию программы для ЭВМ «Программа расчёта деформации пролётной балки двухтележечного мостового крана» (Приложение Б) и «Программа расчёта деформации грузового каната» (Приложение В) в среде программирования Borland Delphi. ВКР была отправлена на конкурс Discovery Science: University-2019 и заняла там первое место в номинации «Практический проект». Наградной диплом представлен в Приложении Г. Объём пояснительной записки – 91 лист и 21 листа графических документов. Работа состоит из введения, пяти глав и заключения. Список литературы содержит 16 источников. / The relevance of the research topic: due to the need to optimize the process of transportation of long loads by bridge cranes with two trucks, to improve the accuracy of positioning of long cargo at its destination with the help of a bridge crane with two trucks and in the introduction of a control system with independent elimination of skewing of long cargo. The purpose of the work: development of control systems for double-axle cranes, designed for accurate transportation of long loads with the possibility of self-regulation and elimination of cargo misalignment. To analyze the factors affecting the accuracy of the movement of long cargo and to provide measures for their accounting in the process of transportation. In the course of the work, the existing methods of coordination of two or more cranes of the designed control system of bridge cranes with trucks with self-removal from the misalignment of goods were considered, the factors affecting the accuracy of positioning were presented and the methods of taking into account certain factors when moving the cargo to the destination were proposed, and a control system for trucks and winches of bridge cranes with trucks was developed. counts the amount of deflection of the steel structures of the crane and the tension of the hoisting rope when you set the value of the vertical movement of the cargo. In the process of working on the master's thesis was issued a priority application for a patent for the invention №2019109823 from 03.04.19 g "bridge crane with two trucks " (the system is presented in paragraph 2.2 of this work). Also sent two applications for state registration of the computer program "Program for calculating the deformation of the span beam of a two-track bridge crane" (Application B) and "program For calculating the deformation of the cargo rope" (Application C) in the programming environment Borland Delphi. Dissertation was sent to the competition Discovery Science: University-2019 and took the first place in the nomination "Practical project". The award diploma is presented in Application D. The scope and explanatory notes – 91 sheet 21 and the sheet graphical documents. The work consists of an introduction, five chapters and a conclusion. The list of references includes 16 sources.

published_or_final_version / Urban Planning / Master / Master of Science in Urban Planning

The main problem with air freight handling at Arlanda is the transportation of freight on airside, that is from the freight terminal to loading process at the aircraft. To approach this problem, a mapping of the physical flow as well as information flow has been made to identify underlying reasons to this problem. This has been the purpose of the study.The mapping has also facilitated the possibilities to identify improvements in the air freight handling process. To give a recommendation of what these improvements could be was the objective of the study.The underlying reasons for the main problem were identified. These causes were space restrictions on the apron, traffic congestion, and lack of freight storage areas by the gates. This aggravates the possibility to prepare freight for each flight departure. The recommendations to Swedavia are long-term measures that should be further explored. These recommendations regard total cost analysis of using fridge containers, co-owned ground handling equipment, IT possibilities,and comparison to other airports.