Subway is the leading fast food franchise chain having over 29.700 branches in 87 countries and differentiating itself among other fast foods by serving healthy food. The chain's focus for further development is concentrated on the countries in Central Europe (Czech Republic, Poland, Hungary and Croatia) and its 47 branches. However, the concept of supply chain in this region is disunited and leads to unfair high costs and high requirements from the branch management. Therefore there is an urgent need to unite the logistic system. The idea is that all the branches in the region will keep two or three local suppliers providing delivery of vegetables, drinks and local specialties; other goods will be distributed by single logistics company in the form of consolidated supply. The new logistic concept for provision of availability of products needed for proper work of all Subway branches in Central and Eastern Europe in context of integration, unification and simplification of logistic chains and its effective management is suggested in the work from the logistic service provider point of view. The task is solved in three parts -- transportation of goods from the producers to the warehouse, its delivery to individual branches, and warehouses itself including the cost calculations. The analysis of supplier's location and the location of supplied branches conclusion follows on locating the warehouse unit near Prague. The kinds of goods could be divided into frozen, cooled, dry and non-food goods. The consumption of individual kinds of goods is specified and the process of supplying the warehouse, means of transport, number of drivers, consolidation on distribution routes and its frequency is suggested. The supply of 47 branches will be done with special means of transport with combined shipping space enabling separate transport of individual kinds of goods by using the mobile screens; on 5 routes always between 7:00 to 23:00 in every country on the same day. The warehouse is a key place for delivery consolidation according to the needs of individual branches in accordance with FIFO principle. About 70 different articles of goods are stocked in three parts; respectively in truss racks with longitudinal filling with capacity of 168 pallet spaces in the height of 4 pallets. The manipulation is provided by low-lift and high-lift trucks. The limit warehouse is rectangular with the area of 122.4 m2, Monthly cost are 485,- Kč for pallet space, the costs in the frozen and cooled warehouse are higher by 15,-Kč per pallet space, that is 500,- Kč. The total costs to supply all the Subway branch restaurants in the whole region is the total sum of costs for good acquisition, its transfer from suppliers to the warehouse, warehouse operations and distribution of goods to individual branches.

We have synthesized a new class of photoaffinity analogs, 2',3'-O-(2,4,6-trinitrophenyl)-8-azido-ATP, -ADP and -AMP (TNP- 8N₃ATP, -ADP and -AMP), and their radiolabeled derivatives, and characterized their interaction with the sarcoplasmic reticulum Ca²⁺-ATPase. The TNP-8N₃-nucleotides were synthesized from ATP in three steps involving bromination in the 8-position of the adenine ring followed by displacement with an azido group and then trinitrophenylation of the resulting 8N₃-nucleotide with TNBS. Inclusion of the oxidizing agent, DTNB, in the final reaction was found to be necessary to prevent reduction of the azido group by the released sulfite anion and also elevated the yield of trinitrophenylation to about 80%. Purity was determined spectrophotometrically, as well as by anion exchange TLC and reversed phase HPLC. In the dark, the compounds were found to display most of the features of the parent TNP-nucleotides and interacted with the Ca²⁺-ATPase in a similar way. When activated by illumination, the probes were specifically incorporated into SR vesicles with high efficiency at alkaline pH. The site of labeling was identified as being on the A₁ tryptic fragment.

Properties of the nucleotide binding site of the Ca²⁺-ATPase of skeletal muscle sarcoplasmic reticulum have been investigated. The study centred around interaction of the high affinity ATP analog, 2'-3'-0-(2,4,6-trinitrophenyl)adenosine 5'-triphosphate, (TNP-ATP), with the Ca²⁺-ATPase. Defined fractions of the sarcoplasmic reticulum (SR), corresponding to the terminal cisternae (TC) and light SR (LSR), were isolated. The TC were shown to have distinctive morphological characteristics that differ from the LSR. The TC vesicles contained electron dense intravesicular material representative of Ca²⁺ binding proteins, and visible membranous "feet" structures, which are reported to interconnect with the transverse tubule. Functional characterisation of the isolated fractions provided evidence for the predominant localisation of Ca²⁺ release channels in TC, and concentration of Ca²⁺-ATPase molecules in LSR. These conclusions were based on the following observations: (a) decreased Ca²⁺ transport of TC versus LSR; ruthenium red, a Ca²⁺ channel blocker, enhanced Ca²⁺ transport and pumping efficiency in TC, (b) higher Ca²⁺-ATPase activity for LSR in the presence and absence of ionophore, (c) rapid Ca²⁺ efflux from TC which is inhibited by ruthenium red. Of special interest was the characterisation of the TC and LSR with respect to turnover-dependent TNP-ATP fluorescence. Fluorescence observed for TC was approximately 65% of that for LSR. This phenomenon may be attributable to either the decreased Ca²⁺ ATPase content of the TC vesicles or open Ca²⁺ release channels. Hence the TNP-ATP fluorescence characteristics appear to reflect the morphological and functional subspecialisation of the defined SR fractions.

Kvantprickar är intressanta för tillverkning av solceller på grund av möjligheten att justera bandgapet beroende på kvantpricksstorleken. I detta examensarbete har alternativa arkitekturer av PbS kvantprickssolceller testats samt att påverkan av olika lager har utvärderats. Först framställdes en kort reproducerbarhetsstudie av PbS kvantprickssolceller, där de tillverkade solcellerna gav låg effektivitet jämfört med litteraturen. En jämförelse av att använda ZnO eller magnesiumdopat ZnO (MZO) utfördes, där solcellerna med MZO presterade bättre än solcellerna med ZnO. Vidare testades påverkan av att ta bort hål- jämfört med elektrontransporterande lagret, där det elektrontransporterande lagret visade sig vara väsentligt för att solcellen skulle fungera medan solcellen fortfarande kunde fungera utan det håltransporterande lagret. Dessutom testades en inverterad solcellstruktur, där alla producerade solceller hade en effektivitet under 0,09 %. Det testades också att använda en annan ligandlösning och lösningsmedel för det ligandutbyte som behövs för det ljusabsorberande kvantprickslagret i solcellen. Detta gjordes med ammoniumjodid för ligandutbytet för att senare använda lösningmedlet propylenkarbonat, filmerna som producerades med det nya ligandutbytet var av dålig kvalitet och gav solceller med låg effektivitet. Slutligen genomfördes en kort studie av glödgningstemperaturen för ett tunt lager av MZO, där man fann att MZO kristalliserade vid 250℃, 300℃ och 350℃ när det glödgades i 30 minuter. / Quantum dots are of great interest for producing solar cells due to the possibility of tuning the bandgap depending on the quantum dot size. In this Masters's thesis project alternative architectures of PbS quantum dot solar cells have been tested and the influences of different layers have been evaluated. First, a short reproducibility study of the PbS quantum dot solar cell was produced, where it could be seen that the fabricated solar cells gave low efficiencies compared to literature. A comparison of using ZnO or magnesium doped ZnO (MZO) was performed, where the solar cells using MZO performed better than the solar cells using ZnO. Furthermore, the influence of removing the hole compared to the electron transporting layer was tested, where the electron transporting layer proved to be essential for the solar cell to function while it still could function without the hole transporting layer. Additionally, an inverted solar cell structure was tested, but only produced solar cells with efficiencies below 0.09 %. It was also tested to use another ligand solution and solvent for the ligand exchange needed for the light-absorbing quantum dot layer in the solar cell. This was done using ammonium iodide for the ligand exchange to later disperse the quantum dots in propylene carbonate, although the films produced with the new ligand exchange were of poor quality and gave low-efficiency solar cells. Lastly, a short study of the annealing temperature of an MZO thin-film was realised, where it was found that the MZO crystallised at 250℃, 300℃, and 350℃ when annealed for 30 minutes.

<p>Insects are continually exposed to potentially toxic endogenous compounds and xenobiotics that require rapid elimination from the body. Xenobiotic resistance in insects has evolved predominantly by increasing the activity of detoxification enzymes and/or by increasing toxin excretion via the Malpighian (renal) tubules. The tubules have long been known to transport organic anions at high rates. This thesis examines the mechanisms of excretion and detoxification of the organic anion methotrexate (MTX) by isolated tissues of the fruit fly <em>Drosophila melanogaster</em>. A radioisotope tracer technique and the Ramsay assay were used to measure MTX secretion. Quantitative PCR (qPCR) was used to evaluate the expression of the genes for putative organic anion transporters. My results show that MTX transport across the Malpighian tubule epithelium is active, saturable, Na⁺-independent and inhibited by a wide range of organic anions including MK-571, probenecid and Texas Red. Pharmacological studies and qPCR analyses suggest multiple transporters are involved in the movement of MTX across the Malpighian tubules. Moreover, chronic exposure of larvae to dietary MTX or salicylate dramatically increases the transepithelial transport of MTX by isolated Malpighian tubules, suggesting that excretion of MTX is upregulated by exposure to these organic anions in the diet. In addition, treatments known to increase expression of specific detoxification enzymes, such as the P450 monoxygenases (P450s) and the glutathione-S-transferases (GSTs), also led to an increase in expression levels of multidrug efflux transporter (MET), multidrug resistance like protein 1 (dMRP) as well as to increased secretion of MTX by the tubules. This latter finding suggests a coordinated response to toxin exposure, so that when detoxification pathways are increased, there is a corresponding increase in the capacity for elimination of the products of P450 and GST enzymes. Finally, the last section of this thesis has shown that RNAi knockdown of a single organic anion transporter gene in the principal cells of <em>D. melanogaster</em> Malpighian tubules is associated with reductions in the expression of multiple, functionally-related genes. Importantly, these results indicate that dMRP andMET are not the dominantMTX transporters in the tubules when flies are reared onMTX-enriched diets. However, reductions in the expression of organic anion transporting polypeptide (OATP) are associated with reduced secretion of the organic anionsMTX, fluorescein and Texas Red. Taken together, these results suggest that OATP and at least one additional transporter, as yet unidentified, are required forMTX secretion. In conclusion, the results of my research contribute to our understanding of the mechanisms of organic anion detoxification and excretion in flies exposed to dietary toxins.</p> / Doctor of Science (PhD)

Följande studie har utförts på begäran av energiföretaget Norrenergi AB, där det finns en önskan att tillförlitlighetssäkra den nuvarande driften av stofttransportsystemet tillhörande två av värmeverkets hetvattenpannor. Studien har undersökt huruvida det finns möjlighet att framförallt minska underhållskostnaderna. Studien har framförallt inriktats mot två stofttransportfläktar som vardera tillhör ett stofttransportsystem, eftersom mycket underhållsarbete lagts på de fläktarna. En jämförelse med andra liknande verk har även utförts då det visats att Norrenergi AB:s lösning av stofttransporten är ytterst ovanlig. Vidare har en analys av fläktarna utförts, vilken visade att de är underdimensionerade för systemet. Det har konstaterats utifrån genomförda SPM-, temperatur- och bullermätningar. Olika typer av lösningar på problemet har undersökts och då på en förändring av hela systemet, alternativt enbart av fläktarna eller lagren till stofttransportfläktarna. Rapporten har utmynnat i flera förslag vilka innefattar en ny systemutformning, installation av nya fläktar samt en uppgradering av det nuvarande systemet, där installation av nya fläktar rekommenderas. / This study has been carried out at the request by the energy company Norrenergi AB. It consists of an analysis on how they can reduce the maintenance regarding two dust transporting fans installed in the flue gas cleaning compartment of their thermal power plant. The study also compares what solutions other plants have regarding the dust-transport. The solution installed at Norrenergi AB was found to be rather unusual. Measurements and calculations have been performed to investigate further what have caused the high maintenance on the fans. The study looks into what upgrades are available to the entire dust transporting system. The result of the study turned into different suggestions, which includes a new configuration of the dust transporting system, and installation of new fans and also an upgrade of the existing dust transporting system. Among the suggestions the final recommendation is the alternative of installing new fans.

Ce travail de thèse a permis de concevoir, synthétiser et caractériser de nouveaux verres moléculaires à base de carbazole pour la réalisation de cellules solaires DSSC solide ou de type pérovskite. Ces structures sont une alternative à la molécule de référence à base de spirobifluorène (Spiro-OMeTAD) utilisée majoritairement dans les dispositifs hybrides. Nous avons optimisé une voie de synthèse simple et rapide d’un « synthon carbazole » servant de précurseur à la conception d’une large variété de verres moléculaires transporteur de trous (HTM). Cette voie de synthèse a ainsi permis de réaliser une première génération de molécules possédant un unique synthon carbazole substitué par des groupements aryles (naphtalène, pyrène, triazatruxène) puis une seconde génération incorporant deux synthons carbazole séparés par un espaceur alkylé. Dans les deux cas, les voies de synthèse sont simples et les rendements de conversion d’énergie générés en DSSC solides sont prometteurs (entre 2,22 et 2,47 % avec le colorant D102). Une étude préliminaire de vieillissement consistant à analyser la dégradation en thermolyse et photolyse d’un film mince utilisant un HTM carbazole montre que ce dernier (Cz-P) possède une stabilité comparable au Spiro-OMeTAD en absence de dioxygène. Finalement, deux verres moléculaires ont été étudiés en cellules de type pérovskite permettant d’atteindre des rendement de conversion de 13,08 % et 12,41 % (pour Cz-P et Cz-PF) quasi-identiques à ceux à base de Spiro-OMeTAD (13,45 %) confirmant que ces structures à base de synthon carbazole sont aussi de bons candidats pour la réalisation de cellule pérovskite performantes. / The aim of this work was to design, synthesize and characterize new carbazole based molecular glasses for the realization of solid state DSSC or perovskite solar cells. These structures would be an alternative to the reference molecule based on spirobifluorene (Spiro-OMeTAD) mainly used in hybrid devices. We have optimized a simple way to synthetize a "synthon" as a precursor to the design of a wide variety of efficient hole transporting materials (HTM). This synthesis pathway has allowed producing a first generation of molecules based on a single carbazole synthon substituted by aryl groups (naphthalene, pyrene, triazatruxene) then a second generation incorporating two carbazole synthons separated by an alkyl spacer. In both cases, the synthesis pathways are simple and the energy conversion efficiencies generated in solid DSSCs are promising (between 2.22 % and 2.47 % with the D102 dye). A preliminary ageing study has consisted in analyzing the degradation during thermolysis or photolysis of a carbazole based thin film. It was shown that Cz-P possesses stability similar to Spiro-OMeTAD in the absence of oxygen. Finally, two carbazole molecular glasses were studied in perovskite cells to achieve conversion efficiencies of 13.08 % and 12.41 % (for Cz-P and Cz-PF respectively) almost identical to the one based on Spiro-OMeTAD (13.45 %), confirming that these carbazole based structures are good candidates for the realization of efficient perovskite cells.

Este trabalho tem como objetivo global contribuir para o desenvolvimento do estudo da propagação de ondas em dutos de transporte de fluidos, especialmente oleodutos e gasodutos, através da análise da atenuação acústica e da velocidade de propagação da onda. Para isso, foram feitos ensaios experimentais, tanto em escoamento mono quanto bifásico, variando-se a vazão do escoamento em uma linha de testes de 1500 metros e 50 mm de diâmetro, para aquisição de sinais gerados a partir do fechamento de válvulas de simulação de vazamentos em pontos ao longo da tubulação. Para análise da atenuação acústica foi proposta uma metodologia baseada na medição do coeficiente de amortecimento temporal das ondas de pressão como subsídio para o cálculo do coeficiente de atenuação, através da utilização de um único sensor de pressão. Esta metodologia foi validada pela medição direta do coeficiente de atenuação e os resultados mostram uma excelente concordância em escoamentos monofásicos. Para os testes em escoamento bifásico não foi possível aplicar esta metodologia devido ao forte amortecimento das ondas de pressão, sendo feitas apenas medições diretas da atenuação com resultados fenomenologicamente coerentes. A velocidade de propagação acústica para escoamento monofásico foi influenciada pela presença de gás dissolvido e bolhas de cavitação, apresentando valores próximos aos da literatura para baixas vazões de escoamento. Para altas vazões, as velocidades foram compatíveis com o escoamento bifásico a bolhas finamente dispersas. Para o escoamento bifásico o regime de escoamento variou de bolhas a pistonado. As velocidades de propagação obtidas são compatíveis com aquelas obtidas por modelos teóricos. / This work aims to contribute to the development of the study of wave propagation in fluid transport pipelines, through the analysis of acoustic attenuation and propagation speed. For this reason, experimental tests were made in single and two-phase flow, varying the flow rate in a test line of 1500 meters and 50 mm in diameter, for the acquisition of signals generated from the closing of leak simulation valves at known points along the pipeline. To analyze the acoustic attenuation it was proposed a methodology based on measurement of temporal damping coefficient of pressure waves as input for calculating the attenuation coefficient, by using a single pressure sensor. This methodology was validated by direct measurement of attenuation coefficient and the results show an excellent agreement in single-phase flow. For the tests in two-phase flow it was not possible to apply this methodology due to the strong damping of pressure waves, which only made direct measurements of attenuation results phenomenologically consistent. Acoustic propagation velocity for single phase flow was influenced by the presence of dissolved gas and cavitation bubbles, having values close to the literature for low flow rates. For high flows rates, the velocities were consistent with a two-phase flow at finely dispersed bubbles. For the two-phase flow the regime varied from slug to bubbles. The propagation velocities obtained are consistent with those obtained by theoretical models.

Este trabalho tem como objetivo global contribuir para o desenvolvimento do estudo da propagação de ondas em dutos de transporte de fluidos, especialmente oleodutos e gasodutos, através da análise da atenuação acústica e da velocidade de propagação da onda. Para isso, foram feitos ensaios experimentais, tanto em escoamento mono quanto bifásico, variando-se a vazão do escoamento em uma linha de testes de 1500 metros e 50 mm de diâmetro, para aquisição de sinais gerados a partir do fechamento de válvulas de simulação de vazamentos em pontos ao longo da tubulação. Para análise da atenuação acústica foi proposta uma metodologia baseada na medição do coeficiente de amortecimento temporal das ondas de pressão como subsídio para o cálculo do coeficiente de atenuação, através da utilização de um único sensor de pressão. Esta metodologia foi validada pela medição direta do coeficiente de atenuação e os resultados mostram uma excelente concordância em escoamentos monofásicos. Para os testes em escoamento bifásico não foi possível aplicar esta metodologia devido ao forte amortecimento das ondas de pressão, sendo feitas apenas medições diretas da atenuação com resultados fenomenologicamente coerentes. A velocidade de propagação acústica para escoamento monofásico foi influenciada pela presença de gás dissolvido e bolhas de cavitação, apresentando valores próximos aos da literatura para baixas vazões de escoamento. Para altas vazões, as velocidades foram compatíveis com o escoamento bifásico a bolhas finamente dispersas. Para o escoamento bifásico o regime de escoamento variou de bolhas a pistonado. As velocidades de propagação obtidas são compatíveis com aquelas obtidas por modelos teóricos. / This work aims to contribute to the development of the study of wave propagation in fluid transport pipelines, through the analysis of acoustic attenuation and propagation speed. For this reason, experimental tests were made in single and two-phase flow, varying the flow rate in a test line of 1500 meters and 50 mm in diameter, for the acquisition of signals generated from the closing of leak simulation valves at known points along the pipeline. To analyze the acoustic attenuation it was proposed a methodology based on measurement of temporal damping coefficient of pressure waves as input for calculating the attenuation coefficient, by using a single pressure sensor. This methodology was validated by direct measurement of attenuation coefficient and the results show an excellent agreement in single-phase flow. For the tests in two-phase flow it was not possible to apply this methodology due to the strong damping of pressure waves, which only made direct measurements of attenuation results phenomenologically consistent. Acoustic propagation velocity for single phase flow was influenced by the presence of dissolved gas and cavitation bubbles, having values close to the literature for low flow rates. For high flows rates, the velocities were consistent with a two-phase flow at finely dispersed bubbles. For the two-phase flow the regime varied from slug to bubbles. The propagation velocities obtained are consistent with those obtained by theoretical models.

Abstract This study utilized normal and defective epithelial cell cultures and epidermal skin samples to examine intra- and intercellular calcium signaling. The main interests of this thesis were Hailey-Hailey disease (HHD), Darier disease (DD), neurofibromatosis 1 (NF1) and transitional cell carcinoma (TCC). HHD and DD diseases are rare autosomal dominant skin disorders characterized by dissociation of epidermal keratinocytes (acantholysis) at the suprabasal layer of the epidermis. HHD and DD diseases are caused by mutations in the genes encoding the calcium pumps in the Golgi apparatus (hSPCA1) and endoplasmic reticulum (SERCA2b), respectively. Due to these mutations calcium uptake into the Golgi apparatus or ER is diminished, which is believed to cause abnormal cell junction protein processing and dissociation of keratinocytes. This study utilized electron probe microanalysis (EPMA) and demonstrated for the first time that lesional areas of HHD and DD and non-lesional areas of DD epidermis display abnormally low calcium content in the basal cell layer. Furthermore, ATP mediated calcium signaling was impaired in cultured HHD and DD keratinocytes and epidermal ATP receptor localization was disrupted. In conclusion, these results suggest that the low calcium content in the basal cell layer is the reason for suprabasal ruptures in HHD but not necessarily in DD lesions, and that abnormal ATP receptor localization contributes to the calcium signaling defects. NF1 deficient keratinocytes display abnormally low resting cytosolic calcium levels and it has been suggested that the calcium concentration in the lumen of the endoplasmic reticulum is decreased. This study demonstrated that NF1 keratinocytes rely mostly on ATP mediated calcium signaling while normal keratinocytes rely mostly on gap junctional intercellular communication (GJIC). Studies with TCC cells have demonstrated that gap junctions participate in intercellular calcium wave propagation. This thesis demonstrated that the ATP mediated pathway was also operational in calcium wave propagation in normal uroepithelial and TCC cell cultures. Furthermore, impaired calcium wave propagation in the TCC cell culture could be improved through PKC α/βI –isoenzyme inhibition with Gö6976. Gö6976 treatment increased connexin 26 clustering at plasma membrane but did not alter expression level of the protein. This thesis contains a wide repertoire of calcium detection techniques including a new cutting-edge technology for elemental calcium detection of epidermal samples. These techniques can be used for molecular specific analysis of calcium signaling in epithelial cells.