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Detta examensarbete är genomfört åt Sandvik Mining and Construction inom ramen för det statliga samarbetsprojektet MinBaS II. Sandvik Mining and Construction är ett av Sandvik koncernens affärsområden och har en världsledande position på marknaden för maskiner och tekniska lösningar för bergbrytning m.m MinBas II är ett samarbetsprojekt mellan ett stort antal företag och universitet där staten står som huvudman och löper till 2010. Uppgiften med examensarbetet var att se om det fanns någon metod för att kartlägga de interna transporterna och beräkna deras energiåtgång i en bergtäckt. I brist på en befintlig skulle det tas fram en ny metod och sedan testa denna genom att genomföra fältstudier i en bergtäkt tillhörande Skånska Makadam AB för att sedan göra beräkningar på energiåtgången där. Volvo CE har under arbetet ställt upp med information och även givit oss SiteSimulation, ett simuleringsprogram för simulering av användning av deras maskiner. En del av arbetet var också att utreda hur energiåtgången ändras om förkrossen placeras på en högre respektive lägre nivå än det ställe där bergbrytningen genomförs. För att införskaffa underlag till beräkningarna har fältstudier genomförts i Skånska Makadam AB:s bergtäkt. Där gjordes bl.a. uppmätningar av den fysiska miljön som t.ex. mätningar av höjdskillnader, bedömningar av lutningar på backar och bedömningar av vägstandarder. Dessutom gjordes ett antal klockningar av cykeltider för olika fordon vilket senare fick fungera som underlag för att utvärdera hur vida Site Simulations resultat stämmer överens med verkligheten. I resultatet går det att utläsa vilken den totala energi- och bränsleförbrukningen per ton är för respektive utvald produkt. Dessa värden är en sammanställning av förbrukningarna för de olika interna transporter som behövs under tillverkningsprocessen, från bergbrytning till kundutlastning av färdig produkt. Arbetet med att utreda förkrossens placering genomfördes genom att en teoretisk sträcka ”tillverkades” i Site Simulation där sedan förkrossen placerades på olika nivåer i förhållande till startstället. De olika simuleringarna tydde på att optimal bränsleförbrukning uppnås vid en lätt sluttning mot förkrossen. Vid simuleringarna med de nya Volvo maskinerna, gick det av resultaten att dra slutsatsen att energiåtgången per ton sten ökar samtidigt som även produktiviteten ökar. Till sist kan vi dra slutsatsen att det hela bygger på att man gör en ordentlig förstudie och verkligen planerar upplägget av anläggningen vilket allt ifrån lagringshögar, transportsträckor och placering av krossanläggning i förhållande till dessa.

Förutsättningarna för arbete inom CSR (Corporate Social Responsibility) ser olika ut från bransch till bransch. Idag föreligger det problematik kring uppfattningen vad CSR innefattar. En underrubrik till CSR är miljöansvar. Författaren Subhabrata (2008) diskuterar hur miljöpåverkande företag, exempelvis transportföretag, kan vara miljömedvetna trots verksamma i en smutsig bransch. Examensarbetet ämnar förstärka och utveckla tidigare forskning inom området miljöansvar genom att empirisk belysa paradoxen mellan ett transportföretag och deras miljöansvar. Utifrån denna paradox ämnar examensarbetet till att ge en ökad förståelse för hur transportföretag ska kunna kommunicera sitt miljöansvar trots den problematik som föreligger. Insamlad primärdata utgör den huvudsakliga källan och har skett genom kvalitativa intervjuer samt en kvantitativ enkätundersökning. Den teoretiska referensramen består främst av Beckmann och Morsings (2006) teori, strategisk CSR kommunikation. En gapmodell har applicerats på fallföretaget Jetpak för att få förståelse hur transportföretag som är verksamma i en smutsig bransch ska kunna kommunicera sitt miljöansvar utan att uppfattas som paradoxala. Examensarbetet har empiriskt belyst och visat att det existerar en viss skillnad i hur Jetpak och befintliga kunder uppfattar miljöansvar. Beställningsunderlag och webbsida är kommunikationskanaler kunder vill ska nyttjas. Vidare att en tvåvägskommunikation är en strategi Jetpak bör använda för att förbättra extern kommunikation. Detta då en dialog kring paradoxen kan vidtas för att undvika avvikande uppfattningar hur ett transportföretag ska ta miljöansvar. Dock återstår problematik kring vad som exakt ska kommuniceras för att uppnå optimal kundnöjdhet, men vi kan konstatera att ISO-certifiering och miljöcertifierade bilar är viktigt kommunikationsinnehåll.

Universiẗat, Diss.--Heidelberg, 2006. / Zsfassung in dt. u. engl. Sprache.

Campylobacter jejuni is a human pathogen that causes severe diarrhea! disease. However, our understanding of C. jejuni virulence mechanisms and survival during disease and transmission remains limited. Amino acid ATP Binding Cassette (AA-ABC) transporters in C. jejuni have been proposed as being important for bacterial physiology and pathogenesis. We have investigated a novel AA-ABC transporter system, encoded by cj0467-9, by generating targeted deletions of cj0467 (membrane transport component) and cj0469 (ATPase component) in C. jejuni 81-176. Analyses described herein have led us to designate these genes paqP and paqQ, respectively [pathogenesis-ssociated glutamine (q) ABC transporter permease () and ATPase (Q)]. We found that loss of either component resulted in amino acid uptake defects, most notably diminished glutamine uptake. Both ΔpaqP and ΔpaqQ mutants also exhibited a surprising but significant increase in short-term intracellular survival in macrophages and epithelial cells. Levels of resistance to a series of environmental and in vivo stresses were examined. Both mutants were hyper-resistant to aerobic and oxidative stress, and while ΔpaqP was also hyper-resistant to heat and osmotic shock, ΔpaqQ was more susceptible than wild-type to the latter two stresses. Annexin-V staining coupled with fluorescence microscopy revealed that macrophages infected with the ΔpaqP and ΔpaqQ mutants underwent a lower level of apoptosis than cells infected with wild-type bacteria. Macrophages infected with the mutant strains exhibited a transient decrease in ERK activation compared to wild type-infected macrophages, potentially explaining the reduced apoptosis phenotype. The ΔpaqP mutant did not exhibit a defect for short or longer term mouse colonization, consistent with its increased stress survival and diminished host cell damage phenotypes. Collectively, these results demonstrate a unique correlation between an AA-ABC transporter with bacterial stress tolerance, intracellular survival, host cell damage, and host signal transduction in response to pathogen infection.

Campylobacter jejuni is a human pathogen that causes severe diarrhea! disease. However, our understanding of C. jejuni virulence mechanisms and survival during disease and transmission remains limited. Amino acid ATP Binding Cassette (AA-ABC) transporters in C. jejuni have been proposed as being important for bacterial physiology and pathogenesis. We have investigated a novel AA-ABC transporter system, encoded by cj0467-9, by generating targeted deletions of cj0467 (membrane transport component) and cj0469 (ATPase component) in C. jejuni 81-176. Analyses described herein have led us to designate these genes paqP and paqQ, respectively [pathogenesis-ssociated glutamine (q) ABC transporter permease () and ATPase (Q)]. We found that loss of either component resulted in amino acid uptake defects, most notably diminished glutamine uptake. Both ΔpaqP and ΔpaqQ mutants also exhibited a surprising but significant increase in short-term intracellular survival in macrophages and epithelial cells. Levels of resistance to a series of environmental and in vivo stresses were examined. Both mutants were hyper-resistant to aerobic and oxidative stress, and while ΔpaqP was also hyper-resistant to heat and osmotic shock, ΔpaqQ was more susceptible than wild-type to the latter two stresses. Annexin-V staining coupled with fluorescence microscopy revealed that macrophages infected with the ΔpaqP and ΔpaqQ mutants underwent a lower level of apoptosis than cells infected with wild-type bacteria. Macrophages infected with the mutant strains exhibited a transient decrease in ERK activation compared to wild type-infected macrophages, potentially explaining the reduced apoptosis phenotype. The ΔpaqP mutant did not exhibit a defect for short or longer term mouse colonization, consistent with its increased stress survival and diminished host cell damage phenotypes. Collectively, these results demonstrate a unique correlation between an AA-ABC transporter with bacterial stress tolerance, intracellular survival, host cell damage, and host signal transduction in response to pathogen infection. / Science, Faculty of / Microbiology and Immunology, Department of / Graduate

Elasmobranchs (sharks, skates, and rays) are a primarily carnivorous group of vertebrates that consume very few carbohydrates and have little reliance on glucose as an oxidative fuel, the one exception being the rectal gland. This has led to a dearth of information on glucose transport and metabolism in these fish, as well as the presumption of glucose intolerance. Given their location on the evolutionary tree however, understanding these aspects of their physiology could provide valuable insights into the evolution of glucose homeostasis in vertebrates. In this thesis, the presence of glucose transporters in an elasmobranch was determined and factors regulating their expression were investigated in the North Pacific spiny dogfish (Squalus suckleyi). In particular, the presence of a putative GLUT4 transporter, which was previously thought to have been lost in these fish, was established and its mRNA levels were shown to be upregulated by feeding (intestine, liver, and muscle), glucose injections (liver and muscle), and insulin injections (muscle). These findings, along with that of increases in muscle glycogen synthase mRNA levels and muscle and liver glycogen content, indicate a potentially conserved mechanism for glucose homeostasis in vertebrates, and argue against glucose intolerance in elasmobranchs. In contrast to the other tissues examined, there was a decrease in glut4 mRNA levels within the rectal gland in response to natural feeding, a factor known to activate the gland, suggesting mRNA storage for rapid protein synthesis upon activation. A similar trend was also shown for sglt1 in the rectal gland, and the ability of GLUT and SGLT inhibitors to prevent chloride secretion solidified the importance of glucose uptake for gland function. The exogenous factor of salinity was also investigated and high levels of glut mRNA were observed within the rectal glands of low salinity-acclimated fish relative to control and high salinity fish, reiterating the idea of mRNA storage when the gland is expected to be inactive. Taken together, the results of this thesis demonstrate that glucose is an important fuel in the dogfish (and likely other elasmobranchs) and that the dogfish is fully capable of regulating its storage and circulation, contrary to prior beliefs.

Avian coccidiosis is caused by the intestinal protozoa Eimeria. The parasite"s site of infection in the intestine is site specific. Eimeria acervulina infects the duodenum, E. maxima the jejunum, and E. tenella the ceca. Lesions in the intestinal mucosa cause reduced feed efficiency and body weight gain in Eimeria-challenged chickens. The growth reduction may be due to changes in expression of digestive enzymes and nutrient transporters in the intestine. The objective of this thesis was to examine the expression of digestive enzymes: APN and SI, peptide and amino acid transporters: Pept1, ASCT1, bo,+AT/rBAT, B0AT, CAT1/2, EAAT3, LAT1 and y+LAT1/2, sugar transporters: GLUT1, GLUT2, GLUT5 and SGLT1, mineral transporter: ZNT1 and an immune factor: LEAP2 in the duodenum, jejunum, ileum and ceca of Eimeria-challenged layers and broilers. Comparisons were made between E. acervulina-challenged layers and broilers and E. acervulina, E. maxima and E. tenella-challenged broilers to examine the effect of chicken breeds and Eimeria species, respectively, on digestive enzymes and nutrient transporter expression. E. acervulina-challenged layers and broilers showed downregulation of APN, bo,+AT/rBAT, B0AT, CAT2, EAAT3, GLUT2, SI, ZNT1 and LEAP2 in the duodenum, but not in the jejunum and ileum. E. acervulina-challenged duodenum, E. maxima-challenged jejunum and E. tenella-challenged ceca samples showed common downregulation of APN, GLUT5 and ZNT1. These results demonstrate that there are common changes in intestinal gene expression in response to E. acervulina in broilers and layers, and common changes in response to challenge by different Eimeria species in broilers. / Master of Science

Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Student: Veronika Kučerová Supervisor: doc. PharmDr. Martina Čečková, Ph.D. Consultant: PharmDr. Lenka Ťupová, Ph.D. Title of diploma thesis: Study on expression of selected ABC transporters in placenta The placenta is a temporary organ through which the fetus is supplied with nutrients and oxygen from the mother's blood and conversely waste substances are transferred into the mother's blood during pregnancy. Substance transfer through the placenta is a complex process controlled by a number of physiological mechanisms, including passive diffusion, facilitated diffusion or active transport, which is realized by activity of membrane transporters with energy consumption. Presence of active ABCs efflux transporters in the placenta has been known for a long time and their function is associated primarily with limiting the entry of harmful substances into the placenta and further into the fetus, thus contributing to its protection. Among the best described transporters belong P-glycoprotein (MDR1/ABCB1), breast cancer resistance protein (BCRP/ABCG2) and multidrug resistance protein 2 (MRP2/ABCC2), whose expression has been confirmed in the apical membrane of the placental syncitiotrophoblast facing...

<p>Nucleoside transport into the cell plays a key role in providing building blocks for DNA and RNA synthesis, terminating adenosine signaling, and delivering nucleoside-analog drugs to their targets. Concentrative nucleoside transporters (CNTs) constitute one of the classes of membrane transporters responsible for the cellular uptake of nucleosides and nucleoside-derived drugs. We solved the first structure of a member of the CNT family, vcCNT, by X-ray crystallography, revealing the overall architecture of the transporter, delineating the locations of the nucleoside- and sodium-binding sites, and providing insight into the mechanism of transport. Next we examined the molecular origins of nucleoside and nucleoside-drug selectivity by solving structures of the transporter bound to different nucleosides and drugs and measuring their binding affinities for vcCNT to determine energetically important interactions. We then used this information to design a compound that is better transported by and subtype-selective for human CNTs. Finally, we probed the role of sodium in the ion-coupled transport of nucleosides using binding and transport studies and developed a hypothesis for the structural basis of sodium coupling. Taken together, these studies helped to elucidate the molecular mechanism by which CNTs selectively recognize nucleosides and pump them into the cell and provided insight into drug uptake by these transporters, laying a framework for the improvement of targeted nucleoside-drug delivery by CNTs.</p> / Dissertation