ATP Binding Cassette (ABC) transporters are trans-membrane proteins that exist in all phyla. Mutations in this family of proteins can cause inherited diseases like Cystic Fibrosis. ABC transporters consist of dimers of nucleotide binding domains (NBDs) and transmembrane domains (TMDs). NBDs regulate ABC transporters by binding to and hydrolyzing ATP. Although NBD-ATP interactions, NBD-TMD interactions and NBD-water interactions are known to be crucial to the function of these proteins, it is still not clear what structural and energetic factors are involved in the NBD-NTP interactions, how NBD and TMD interact with each other, how water is involved in the functions of ABC transporters and what are the structures and energetics of protein bound water. Molecular modeling and molecular dynamics (MD) simulations were conducted to interpret and predict the structural and energetic factors in control and action of two ABC transporters, CvaB and SUR2B. Water is essential for ABC transporters to carry out their functions, to increase the accuracy of simulations. Therefore, water potentials in molecular modeling and dynamics simulations were improved based on the calculation of water structures from protein surface. Previous study showed the NBDs of ABC transporter CvaB bind tighter to GTP than to ATP at lower temperature but not at high temperature. The MD simulations in this study suggested the velocity of water molecules initiates the temperature dependent functional change of proteins. Previous study found that Ser1387 in the NBD of SUR2B, an ABC transporter in vascular smooth muscles, is critical to Kir6.1/SUR2B channel. The molecular modeling and dynamics simulation conducted on SUR2B showed that Ser1387 is located at a region that contacts a TMD. Upon the phosphorylation, the interaction between the NBD and TMD was enhanced which led to an inter domain movement. Water is essential for ABC transporters to carry out their functions, to increase the accuracy of simulations, and, therefore, the structures and energetics of protein bound water were studied. The water radial distribution function for protein bound water was calculated from 105 atomic resolution protein crystal structures and was found to be sharper than that observed for bulk water.

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Årsskiftet 2003/2004 trädde Lagen (2003:778) om skydd mot olyckor i kraft. Därmed upphävdes Räddningstjänstlagen. Lagtexten kräver att kommuner skall upprätta en riskhanteringsplan för tänkbara olyckstillfällen. Vänersborgs kommun har beslutat göra så och en del i detta arbete är att sammanställa en riskanalys. Denna rapport innehåller en riskanalys för farligt gods inom Vänersborgs tätort samt riksväg 45. Exempel på farligt gods är brandfarliga vätskor, frätande ämnen och gaser. Vid en riskanalys identifieras alla de risker som kan tänkas vara aktuella. Sannolikheten och konsekvenserna av dessa risker vägs samman till en risknivå, vilken kan åskådliggöras i t.ex. en riskmatris. Med risknivåerna som grund görs en riskvärdering, där storheter omvandlas till dimensionslösa värden (2 döda per 100 år blir t.ex. "låg risk"). Utifrån de värderade riskerna kan beslut tas om eventuella riskreducerande åtgärder. Inom ramen för denna rapport innebär riskerna avåkning eller kollision med läckage av gas, brandfarliga vätskor eller frätande ämnen som följd. Konsekvenserna av detta kan bli toxicitet, frätskador, brand, gasexplosion eller i extrema fall "Boiling Liquid Expanding Vapour Explosion" (BLEVE).

Road transports stand for a great part of Sweden’s total CO2-emissions. Transports are expected to increase over the coming years, and with those the emissions. A greater environmental awareness leads to increased demands for environmentally friendly transport. The aim of this thesis is to study the consequences of changing transportation modes from road to railway. The thesis contains three major parts; a literature study, a case study and analysis with the national freight system Samgods. The literature study intends to give the reader an insight in the potentials as well the obstacles of the railway. Environmental aspects are discussed as well as political views, both positive and negative. Socioeconomic and more company specific incentives that would lead to more transfers from road to railway are presented and discussed. A case study including two companies, Swep and KappAhl, both with relations which transfer potentials they wish to be examined. Differences in costs for today’s truck transportation are calculated and compared to train transportations. The Swedish national freight system, Samgods, is used to examine the distance relationships between closest terminals and final destinations and how intermodal solutions would be designed and the economic consequences thereof. The environmental impacts are calculated for each relation for both companies to present the saving that can be made if the transportation mode is changed, and also to show the companies their environmental impact today at a specific relation. The result of this thesis is that KappAhl would make a great saving when it comes to the CO2-emissions. If they are willing to increase transportation costs with 4.5 % they could reduce their CO2-emissions with 95 % by using the railway instead of only road transportations. For Swep, the comparison between today’s transportation costs and a future cost for railway transport could not be implemented due to non suitable transportation solutions in Samgods. The environmental impact, however, was calculated for today’s transportations and a future railway solution. The result was a great saving for each of the calculated emission types. The analysis made with Samgods showed that freight transported with container is less sensitive to the distance to nearest terminal than freight transported without container. Furthermore, according to Samgods it is cost-effective to transport freight with combined transport if the distance to the final destination is more than 4.6 times the distance to the nearest terminal. The corresponding value for transports without container is 6.9 times. The relationship between nearest terminal and final destination is applicable for distances from 60 km to 300 km from the final destination.

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The transport of phosphate (Pi) between subcellular compartments is central to metabolic regulation. Although some of the transporters involved in controlling the intracellular distribution of Pi have been identified in plants, others are predicted from genetic and biochemical studies. The Arabidopsis thaliana genome encodes a family of six proteins that share similarity with SLC17/type I Pi transporters, a diverse group of animal proteins involved in the transport of Pi, organic anions and chloride. Heterologous expression in yeast, and gene expression and localization studies in plants were used to characterize all six members of this Arabidopsis family, which we have named PHT4. All of the PHT4 proteins mediate Pi transport in yeast with high specificity. Bioinformatic analysis and localization of PHT4-GFP fusion proteins indicate that five of the proteins are targeted to the plastid inner envelope membrane, and the sixth resides in the Golgi apparatus. PHT4 genes are expressed in both roots and leaves although two of the genes are expressed predominantly in leaves and one mostly in roots. These expression patterns, together with Pi transport activities and subcellular locations, suggest roles for PHT4 proteins in the transport of Pi between the cytosol and chloroplasts, heterotrophic plastids and the Golgi apparatus.

This study focuses on carpooling and how carpools can be better integrated into today's society. The purpose of the study is to investigate what affects the motorist’s decisions to become a member of a carpool. The study will highlight the barriers and drivers of membership in a carpool. It is important for the future to change the attitude of motorists and get more motorists to choose more sustainable modes, as is the concept of carpooling is a good solution. The study is based on a qualitative approach with six respondents from the Eskilstuna municipality. The interviews have been analyzed through thematic analysis. The results from the interviews indicate that economy is the most important factor influencing the decision to become a member of a carpool. The barriers with a carpool is convenience and flexibility. Respondents agree that Eskilstuna has good potential to become a sustainable city. They believe that carpools in the future will be a common compromise of having to own a private car. Keywords: Accessibility, sustainable transport, carpool, car-sharing, mobility, motoring / Denna studie syftar till att diskutera bilpooler som hållbart resande för bilisterna i Eskilstuna kommun. Detta för att skapa en förståelse kring vad som påverkar bilisten val av att bli medlem i en bilpool. Vidare ska studien belysa vilka hinder och drivkrafter bilisten ser med att vara medlem i en bilpool. Det är viktigt för framtiden att ändra attityden hos bilisterna och få fler bilister att välja mer hållbara transportsätt och då är konceptet bilpool en bra lösning. Studien har en kvalitativ ansats där sex semistrukturerade intervjuer har genomförts med bilister i Eskilstuna kommun. Intervjuerna har analyserats med den tematiska analysmetoden. Resultatet av intervjuerna visar att ekonomin är den främsta drivkraften till ett medlemskap i en bilpool. De främsta hinderna med ett medlemskap i en bilpool är bekvämlighet och flexibilitet. Respondenterna är överens om att Eskilstuna har goda förutsättningar för att bli en mer hållbar stad i framtiden. De tror att bilpooler i framtiden kommer bli en vanlig kompromiss till att behöva äga en egen bil. För att få fler bilister att välja ett medlemskap i en bilpool krävs det att ändra attityder och bilpooler måste marknadsföras på ett bättre sätt. Nyckelord: Tillgänglighet, hållbara transporter, bilpool, bildelning, mobilitet, bilismen

The dopamine transporter (DAT) is a plasma membrane-bound protein, localized on peri-synaptic terminals of dopaminergic (DA) neurons. DAT is responsible for terminating DA signaling by rapid removal of the transmitter from the synaptic cleft region. DA signaling relies on a critical balance between release and removal of the neurotransmitter within synaptic clefts. Recycling of DAT between intracellular endosomal compartments and the plasma membrane regulates DAT function. This dynamic trafficking occurs in both a constitutive and regulated manner to increase or decrease the number of transporters on the cell surface available for transmitter reuptake. Therapeutic drugs and/or drugs of abuse, including psychostimulants and ethanol, cause maladaptive changes in DA signaling in mesolimbic areas of the brain, leading to addictive behaviors. DAT is the primary site of action for psychostimulants such as, cocaine, methylphenidate, and amphetamine. These drugs can alter the function and/or regulation of the transporter. Ethanol, one of the most widely abused drugs in society, is known to activate DA pathways in reward and reinforcement areas of the brain. However, the effect of ethanol on DAT function and regulation is less clear. The studies presented here explore the action of ethanol on DAT function in mammalian cell systems, and the subcellular trafficking mechanisms that regulate the transporter. To delineate mechanisms of ethanol action on DAT, several lines of HEK-293 cells stably expressing DAT or ethanol-insensitive DAT mutants were generated. Short-term ethanol exposure was found to potentiate DAT function, and ethanol sensitivity is mediated by specific amino acids in the first intracellular loop. This increase in function was accompanied by an enhancement of DAT expressed on the cell surface. The changes in DAT localization and the absence of consensus phosphorylation sites in the ethanol sensitive regions of the transporter, led to the hypothesis that ethanol modulates DAT uptake by altering the dynamic trafficking of the transporter. In the present studies, we found ethanol directly regulates DAT function by altering specific step of the endosomal recycling pathway. Further analysis of the ethanol-sensitive first intracellular loop revealed this region might also play a role in conformational changes required for substrate binding. The findings presented in these studies describe a novel molecular mechanism of ethanol action on DAT, and provide a framework to further understand the action of ethanol on synaptic dopamine regulation. / text

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