Le testicule assure la production des spermatozoïdes et la sécrétion de la testostérone. Chaque fonction est assumée par un compartiment cellulaire distinct: l’épithélium séminifère et le tissu interstitiel. Le cholestérol, présent dans les deux compartiments, est un composé indispensable aux membranes cellulaires et un précurseur essentiel de la testostérone. Dans le compartiment interstitiel, environ 40 % du cholestérol utilisé pour la production hormonale est importé du sang à partir des lipoprotéines HDL et/ou LDL. Dans l’épithélium séminifère, la cellule de Sertoli assure le contrôle et le maintien de la spermatogenèse. Elle a la capacité de synthétiser du cholestérol à partir de l’acétate in vitro, néanmoins, il n’y a pas d’évidence qu’elle le fait in vivo. De plus il existe, au niveau des tubules séminifères, une barrière hémato-testiculaire qui empêche le libre passage de plusieurs composés sanguins, y compris le cholestérol. Nous avons testé l’hypothèse qu’il existe des moyens d’importation du cholestérol sanguin, mais aussi l’exportation du cholestérol intra-tissulaire, qui contourneraient cette barrière et qui contribueraient au maintien du taux intratubulaire du cholestérol compatible avec le bon déroulement de la spermatogenèse. Nous avons comparé les taux de variation de l’expression de l’ARNm et de la protéine des transporteurs sélectifs de cholestérol SR-BI, SR-BII, CD36 et ABCA1 aux taux de variation du cholestérol libre et estérifié au cours de la spermatogenèse chez les souris normales durant le développement postnatal. Afin de mieux apprécier le niveau d’implication de chacun de ces récepteurs, nous avons examiné comment la suppression du gène d’une enzyme comme la lypase hormono-sensible (HSL) ou de celui d’un transporteur de cholestérol comme SR-BI, CD36 ou NPC1 était compensée et comment cette suppression affectait le taux de cholestérol libre et estérifié dans chacun des deux compartiments cellulaires du testicule. Nous avons dans un premier temps mis au point une nouvelle technique d’isolation des testicules en fraction enrichie en tissu interstitiel (ITf) et en tubules séminifères (STf) qui a l’avantage de mieux préserver l’intégrité des formes phosphorylées et glycosylées des protéines comparée aux techniques préexistantes. Les résultats de nos analyses ont montré que l’expression de SR-BI et CD36 étaient maximales dans les ITf au moment où les souris ont complété leur maturité sexuelle et où le niveau de synthèse de la testostérone était maximal. Dans les tubules séminifères, l’expression maximale de SR-BI et le taux le plus élevé de cholestérol estérifié étaient mesurés de façon concomitante à 35 jours après la naissance, au moment où la première vague de l’activité spermatogénétique était complétée. L’expression de l’ABCA1 était maximale au moment où le taux de cholestérol était élevé et minimale au moment où le taux de cholestérol était le plus bas, alors que le niveau d’expression de CD36 était maximal chez l’adulte au moment où le taux de spermiation était le plus élevé. L’expression de SR-BII variait peu dans les deux compartiments cellulaires durant le développement. La suppression génétique de la HSL et de NPC1, qui cause une infertilité chez les souris mâles, était accompagnée d’une accumulation de cholestérol libre et estérifié dans les tubules séminifères. Par contre, la suppression génétique de SR-BI et CD36, qui ne causent pas d’infertilité chez les souris mâles était sans impact significatif sur le taux de cholestérol intratubulaire. Nous avons montré que l’invalidation génétique d’un transporteur sélectif ou d’une enzyme du métabolisme du cholestérol était accompagnée d’un ensemble de mécanismes de compensation visant à maintenir le taux de cholestérol libre aux niveaux semblables à ceux mesurés dans les fractions tissulaires de souris normales. Ensemble, nos résultats ont montré que l’expression des transporteurs sélectifs de cholestérol SR-BI, SR-BII, CD36 et ABCA1 variait en fonction de la spermatogenèse et du taux intratesticulaire du cholestérol suggérant leur contribution au maintien de l’homéostasie du cholestérol intratesticulaire. / The testis is made up of loops of convoluted seminiferous tubules surrounded by interstitial tissue composed of loose connective tissue containing Leydig cells that secrete testosterone into the bloodstream. The seminiferous tubules are lined with a stratified epithelium containing germ cells at various stages of development and the supporting Sertoli cells. Cholesterol is present in both compartments and is crucial for the development of germ cells, the fertility of spermatozoa as well as for testosterone production. In the interstitial compartment, approximately 40 % of the cholesterol used for the hormonal production is imported from blood lipoproteins HDL and LDL. In the seminiferous epithelium, Sertoli cells plays key role in the development and maintenance of spermatogenesis. Sertoli cells have the capacity to synthesize cholesterol from acetate in vitro, however, there is no evidence that they do so in vivo. In addition, there is a blood-testis barrier within the seminiferous tubules that prevents the free passage of several blood compounds including cholesterol. We tested the hypothesis that there are ways of blood cholesterol uptake, but also the intratubular cholesterol efflux that by-pass this barrier and contribute to the cholesterol homeostasis within the tubules. We compared expression patterns of the mRNA and proteins for selective cholesterol transporters SR-BI, SR-BII, CD36 and ABCA1 with those of free and esterified cholesterol during the spermatogenesis in normal mice during the postnatal development. To better appreciate the level of involvement of each receptor, we examined the effect of the deletion of the genes for an enzyme (HSL) or for cholesterol transporters (SR-BI, CD36 or NPC1) on the rate of free and esterified cholesterol in both compartments of the testis. At first, we worked out a new technique to separate the testes into interstitial tissue- (ITf) and seminiferous tubule-enriched fractions (STf) that has the advantage of allowing a more faithful detection of the phosphorylated and glycosylated forms of the proteins compared to existing techniques. Our results showed that the expression of SR-BI and CD36 was maximum in the ITf when mice completed their sexual maturity and reached the peak level of testosterone synthesis. In the seminiferous tubule-enriched fractions, the maximum level of SR-BI expression coincided with the highest level of esterified cholesterol during the development at 35 days, as the first wave of the spermatogenetic activity was completed. ABCA1 reached the highest expression level when cholesterol was high and reached the lowest when cholesterol was at its minimum, while the level of CD36 expression was maximal in the adult tubules as the rate of spermiation was the highest. The knockout of the HSL and NPC1, which renders the male mice infertile, was accompanied by the accumulation of free and esterified cholesterol in the seminiferous tubules. On the other hand, the knockout of SR-BI and CD36, linkes to infertility, did not affect the rate of intratubular cholesterol. Here we showed that genetic withdrawal of a cholesterol transporter or of an enzyme involved in cholesterol metabolism was compensated by other transporters or enzymes in order to maintain the level of free cholesterol similar to those measured in the tissue-enriched fractions of wild-type mice. Together, our results showed that the expression of the selective cholesterol transporters SR-BI, SR-BII, CD36 and ABCA1 varied according to the spermatogenesis and intratesticular cholesterol rate, thus suggesting their contribution to the preservation of the intratesticular cholesterol homeostasis.

Les assemblages supramoléculaires font parties des réactions biochimiques de base dans les fonctions cellulaires (ex: réplication de l'ADN ou réponse immunitaire). Les calix[n]arènes ont été décrit pour interagir avec une large gamme de biomolécules. En conséquence, ils peuvent être trouvés dans de nombreuses applications biologiques tel qu'en diagnostic ou en traitement thérapeutique. Leurs fonctionnalisations sur des nanoparticules d'argent ont produit de nouveaux nano-composés hybrides ayant des propriétés optique, électrique et biologique uniques. Cette thèse a été dédiée à l'étude de ces nano systèmes pour la bio-détection et leurs potentielles applications biomédicales. Le développement de capteur analytique à bas coût, portable et ultra-sensible représente une des attentes majeures dans les applications des calix[n]arènes sur nanoparticules d'argent. Dans cette thèse, ces nano-composés ont été étudiés selon leurs capacités à suivre la micellisation de surfactant mixtes, et pour discriminer un type moléculaire tel qu'une famille d'acide nucléique ou une espèce d'albumine sérique. Dans une deuxième partie, ces nanoparticules hybrides ont été évaluées pour une série d'activités biologiques. Ils ont montré des facultés antibiotiques et anti-oxydantes, de transporter des Ingrédients Pharmaceutiques Actifs, et d'atteindre des cibles antivirales et anticancéreuses / Supramolecular assemblies are among the basic biochemical reactions in the cellular functions (e.g. DNA replication, immune response). Calix[n]arenes are macrocyclic molecules that have been reported for interacting with a wide range of biomolecules. As a consequence, they can be found in many biological applications from diagnosis to therapeutic treatment. Their functionalization on silver nanoparticles have produced new nano hybrid compounds with unique optical, electrical and biochemical properties. This thesis has been dedicated to the study of these nano-systems for bio-sensing and for their potent biomedical applications. Cost effective, portable and ultra-sensitive analytical tools are one of the major expectations of the applications of silver nanoparticles capped with calix[n]arenes. Calix[n]arenes nanoparticles have been reported here for following the micellisation process of mixed surfactants or for discriminating a type of molecule such nucleic acid or a serum albumin specie. In a second part, these hybrid nanoparticles have been evaluated for series of biological activities. They’ve been shown to possess anti-oxidant and antibacterial activities, to transport Active Pharmaceutical Ingredient and to reach antiviral and anti-cancer targets

Arbetet med att minska människans utsläpp av växthusgaser är en fråga som är högaktuell idag. Transportsektorn är den sektor som har näst störst klimatpåverkan inom EU-området. För att minska transportsektorns klimatpåverkan anser EU-kommissionen att en del av det gods som idag går på väg behöver flyttas till tåg eller sjö för att nå EU:s miljömål. Syftet med arbetet var att undersöka skillnaden av växthusgasutsläpp för transport av containrar beroende på transportsätt på sträckan Göteborg till Stockholm. De undersökta transportsätten var lastbil, godståg och containerfartyg. Studien använde en empirisk fallstudie där växthusgasutsläpp beräknades utifrån empiriska bränsleförbruknings data. Fallstudien kompletterades med en intervju från en person med stor erfarenhet av godstransporter på sträckan. Resultatet av undersökningen är att järnvägens miljöverkan är minst, men för tidskänsligt gods är fortfarande vägtransport det effektivaste transportslaget. För att sjöfart ska vara ett miljömässigt alternativ måste anpassningar av fartyg och/eller drift göras. / The work to reduce greenhouse emissions created by humans is a question that is highly relevant today. The transport sector is the second largest emitter of greenhouse gases in the European Union. To reduce the greenhouse emissions from the transport sector the EU commission has said that some of the freight that currently is being transported by road must move to rail or sea transport in order to reach EU environmental targets. The scope of this study is to compare the greenhouse emissions based on fuel consumption from domestic container transport between Gothenburg and Stockholm. The different modes of transports studied were trucks, freight train and container ship. The study was conducted using an empirical case study to calculate the greenhouse gas emissions using empirical fuel consumption data. The case study was supplemented by an interview with a person with great insight in the transport business. The result from the study shows that from an environmental perspective container transport by rail should be used. Transport by road is still the best means of transport for time sensitive cargo. If transport by sea is to be an environmental option, there has to be adjustments on either ships or management or both.

For the transport of their spacecraft from the vehicle assembly building to the launch pads at Kennedy Space Centre, Florida, the National Aeronautics and Space Administration (NASA) is using two special crawler transporters since 1965. First developed for the Saturn V rocket the crawler transporters have been sufficient for all following generations of space ships so far. But for the new generation of Orionspacecraft which is under development now, a load capacity increase for the crawler transporter of plus 50% was necessary. For this task Hunger Hydraulik did develop new jacking, equalizing and levelling (JEL) cylinders with sufficient load capacity but also with some new features to improve the availability, reliability and safety of this system. After design approval and manufacture of the cylinders they have been tested in a special developed one-to-one scale dynamic test rig and after passing this the cylinders had to prove their performance in the crawler transporter itself. This article describes the general application and introduces the technical requirements of this project as well as the realized solution.

The atomic force microscope (AFM) provides a powerful instrument for investigating and manipulating biological samples down to the subnanometer scale. In contrast to other microscopy methods, AFM does not require labeling, staining, nor fixation of samples and allows the specimen to be fully hydrated in buffer solution during the experiments. Moreover, AFM clearly compares in resolution to other techniques. In general, the AFM can be operated in an imaging or a force spectroscopy mode. In the present work, advantage was taken of this versatility to investigate single biomolecules and biomolecular assemblies. A novel approach to investigate the visco-elastic behavior of biomolecules under force was established, using dextran as an example. While a molecule tethered between a solid support and the cantilever tip was stretched at a constant velocity, the thermally driven oscillation of the cantilever was recorded. Analysis of the cantilever Brownian noise provided information about the visco-elastic properties of dextran that corresponded well to parameters obtained by alternative methods. However, the approach presented here was easier to implement and less time-consuming than previously used methods. A computer controlled force-clamp system was set up, circumventing the need for custom built analogue electronics. A commercial PicoForce AFM was extended by two computers which hosted data acquisition hardware. While the first computer recorded data, the second computer drove the AFM bypassing the manufacturer's microscope control software. To do so, a software-based proportional-integral-differential (PID) controller was implemented on the second computer. It allowed the force applied to a molecule to be held constant over time. After tuning of the PID controller, response times obtained using that force-clamp setup were comparable to those of the recently reported analogue systems. The performance of the setup was demonstrated by force-clamp unfolding of a pentameric Ig25 construct and the membrane protein NhaA. In the latter case, short-lived unfolding intermediates that were populated for less than 10 ms, could be revealed. Conventional single-molecule dynamic force spectroscopy was used to unfold the serine:threonine antiporter SteT from Bacillus subtilis, an integral membrane protein. Unfolding force patterns revealed the unfolding barriers stabilizing structural segments of SteT. Ligand binding did not induce new unfolding barriers suggesting that weak interactions with multiple structural segments were involved. In contrast, ligand binding caused changes in the energy landscape of all structural segments, thus turning the protein from a brittle, rigid into a more stable, structurally flexible conformation. Functionally, rigidity in the ligand-free state was thought to facilitate specific ligand binding, while flexibility and increased stability were required for conformational changes associated with substrate translocation. These results support the working model for transmembrane transport proteins that provide alternate access of the binding site to either face of the membrane. Finally, high-resolution imaging was exploited to visualize the extracellular surface of Cx26 gap junction hemichannels (connexons). AFM topographs reveal pH-dependent structural changes of the extracellular connexon surface in presence of HEPES, an aminosulfonate compound. At low pH (< 6.5), connexons showed a narrow and shallow channel entrance, which represented the closed pore. Increasing pH values resulted in a gradual opening of the pore, which was reflected by increasing channel entrance widths and depths. At pH > 7.6 the pore was fully opened and the pore diameter and depth did not increase further. Importantly, coinciding with pore gating a slight rotation of the subunits was observed. In the absence of aminosulfonate compounds, such as HEPES, acidification did not affect pore diameters and depths, retaining the open state. Thus, the intracellular concentration of taurine, a naturally abundant aminosulfonate compound, might be used to tune gap junction sensitivity at low pH.

Background: To reach the global goals of 2030, changes need to be maderegarding how decision makers decide to freight their goods. In Sweden,road traffic is held accountable for 90% of the carbon dioxide emissions.To help solve the problem with vast distances in Sweden's rural areas,scientists have researched the possibility of coordinating the transports.The research has shown that transports receive a more appropriate fill rate,lower transportation costs, and because of those two factors, lowered theircarbon dioxide emissions. Purpose: The purpose of this study is to lay a scientific foundation andpresent an example of a decision model. The decision model mainly aimstowards decision makers in rural municipalities but also companies thatwork toward these rural areas.  Methodology: This research undertook a qualitative research approach inan exploratory method. In order to ensure that the criteria’s and the prosand cons with coordinating freight transports the researchers interviewedkey persons for the rural municipalities in a semi structured or structurednature. Findings: The study has found the most relevant pros and cons with acoordination of freight transports and the criteria’s needed to build anexample of a decision model.  Conclusions: The theoretical and empirical data has been similar in many,but one stands out, and that is the increase of lead times as a negativefactor the rural areas, because of the coordination. The citizens andcompanies these rural areas are more interested in consistency andreliability. The study concluded the necessary criteria’s needed to build thedecision model. / Bakgrund: För att Sverige ska kunna nå sina uppsatta klimatmål innan år2030, behövs stora förändringar ske i hur vi skickar och transporterar vårtgods. Idag står Sveriges vägtrafik för 90% av de koldioxidutsläpp somsker av alla inrikes transporter. För att lösa problemet med de långaavstånden ut mot glesbygden har man undersökt möjligheten till attförsöka samordna varutransporterna som ska till glesbygdsområden.Tidigare varusamordningsprojekt har visat sig tillföra starka fördelar förtransportföretag som bland annat bättre fyllnadsgrad och reduceradetransportkostnader, samtidigt som att man minskar utsläppen kopplade tilltransporter. Syfte: Studiens syfte är att lägga en vetenskaplig grund förvarusamordning samt presentera en beslutsmodell. Beslutsmodellen riktarsig mot kommunala beslutsfattare samt beslutsfattare inom företag somjobbar mot glesbygder. Metod: Studien har utförts enligt ramverket för en kvalitativ intervjustudiemed en explorativ forskningsdesign. Detta för att författarna ska ha frihetatt arbeta passande efter situationen då det är ett relativt outforskat ämne. Analys och resultat: I studiens resultat presenteras delsvarusamordningens olika fördelar, dels dess nackdelar. Dessa för- ochnackdelar är tänkta att synliggöra varusamordningens möjligheter samttillkortakommanden.Vidare presenteras en beslutsmodell med förslag på beslutskriterier somtagits fram från de teoretiska och empiriska information som insamladestill studien.

No description available.

La mélatonine est une neurohormone produite principalement par la glande pinéale de manière circadienne et agissant par l’activation de deux récepteurs couplés aux protéines G (RCPGs) appelés MT1 et MT2. La mélatonine régule de nombreuses fonctions physiologiques importantes. La régulation des niveaux de dopamine (DA) et de glucose en font partie mais nous ne savons pas clairement comment la mélatonine les régule.Les niveaux de DA extracellulaire sont principalement régulés par son transporteur (DAT) responsable de sa recapture dans les neurones présynaptiques afin de prévenir d’une hyperactivation des récepteurs dopaminergiques. Par conséquent, nous avons vérifié le rôle de DAT dans la régulation du système dopaminergique par le système mélatoninergique. Nous avons montré qu’en interagissant avec la forme immature non-glycosylée de DAT, MT1 et MT2 le retiennent dans le réticulum endoplasmique régulant ainsi son expression à la surface cellulaire et donc la recapture de la DA. De la même manière, les souris déficientes en MT1 ou MT2 ont montré une augmentation de la recapture de la DA dans les synaptosomes de striatum et une baisse de l’hypermotilité induite par l’amphétamine. Dans ce projet nous avons ainsi révélé un nouveau lien entre les systèmes mélatoninergiques et dopaminergiques basé sur la formation de complexes moléculaires entre les récepteurs de la mélatonine et DAT.Afin de mieux comprendre le rôle de la mélatonine dans la régulation des niveaux de glucose, nous avons ensuite étudié l’implication de variants génétiques de MT2 dans le développement du diabète de type 2 (DT2). Des études antérieures avaient montré que des variants naturels défectueux fonctionnellement étaient associés à un risque de développer le DT2. Afin de déterminer plus précisément les propriétés défectueuses en lien avec le DT2, nous avons mesuré l’activation spontanée et celle induite par la mélatonine de 40 variants MT2. Nous avons ainsi montré que des défauts d’activation des protéines Gαi et Gαz induite par la mélatonine et de recrutement spontané de la βarrestine-2 sont significativement reliés à un risque de développer le DT2. Les résultats expérimentaux corrélaient avec les prédictions de l’analyse sur le score d’évolution. Ce travail permettra de nouvelles avancées dans la recherche de traitements personnalisés pour les personnes portants les mutations sur MT2 afin qu’il retrouve une réponse non défectueuse.Le séquençage de 9393 personnes a permis l’identification de 32 variants naturels MT1. Le récepteur MT1 sauvage et les variants ont ainsi été caractérisés grâce aux techniques de transfert d’énergie par résonnance de bioluminescence (BRET). Nous avons montré que MT1 active les protéines Gαi/o, Gα12 et Gα15 et recrute la βarrestine-2. L’analyse des résultats par factorisation matricielle non linéaire a révélé l’existence de 5 clusters caractérisés par différents profils de signalisation. La modélisation 3D par homologie de MT1 a permis de déterminer l’impact de chaque variant sur l’activation du récepteur et ses interactions avec les protéines G et la βarrestine-2. Ce projet a ainsi permis de démontrer que des variants naturels sont très intéressant afin de comprendre les mécanismes d’action des RCPGs. En résumé, ce travail contribue à la compréhension des fonctions des récepteurs à la mélatonine et souligne leur importance dans la régulation du système dopaminergique et de l’homéostasie glucidique. Nos résultats offrent de nouvelles perspectives dans la recherche de nouveaux traitements personnalisés pour les patients souffrant d’un dérèglement du système dopaminergique ou de DT2. / Melatonin is a neurohormone mainly released from the pineal gland in a circadian manner acting through two G protein-coupled receptors (GPCRs) called MT1 and MT2. Melatonin regulates many important physiological functions. Regulation of dopamine (DA) and glucose levels are two of them but how they do this is not clear.Extracellular DA levels are mainly regulated by its transporter (DAT) which mediates DA re-uptake into presynaptic nerve termini to prevent DA receptor hyperactivation in the presynaptic cleft. Consequently, we verified the role of DAT in the regulation of the DA system by melatonin. We showed that MT1 and MT2, by interacting with the immature non-glycosylated form of DAT retain DAT in the endoplasmic reticulum thus regulating DAT cell surface expression and DA reuptake. Consistently, mice with targeted deletion of MT1 and MT2 show markedly enhanced DA uptake in striatal synaptosomes and decreased amphetamine-induced locomotor activity. Collectively, we revealed here a molecular link between the melatonin and DA systems, which is based on the formation of a molecular complex between melatonin receptors and DAT.To better understand the role of melatonin on the regulation of glucose levels, we studied the involvement of genetic variants of MT2 in the development of type 2 diabetes (T2D). Previous studies showed that natural loss-of-function variants of MT2 associate with T2D risk. To determine more precisely the defective properties linked to T2D risk we monitored spontaneous and melatonin-induced activation of different signaling pathways by 40 MT2 variants. We show that defects in melatonin-induced Gαi and Gαz activation and spontaneous βarrestin-2 recruitment are most significantly associated to T2D risk. Experimental results correlated well with those predicted by evolutionary lineage analysis. This work will help to propose personalized treatments for MT2 variant carriers to recover their defective responses.Sequencing of 9393 individuals resulted in the identification of 32 natural MT1 variants. MT1 wild-type and variants were functionally characterized in bioluminescence resonance energy transfer (BRET) assays. We showed that MT1 activates Gαi/o, Gα12 and Gα15 proteins and recruits βarrestin-2. Analyzes of results by non-linear matrix factorization revealed the existence of 5 clusters characterized by different signaling profiles. Computational homology modeling of the 3D model of MT1 helped to determine the impact of each variant on receptor activation and interaction with G proteins and βarrestin-2. Collectively, our data illustrate that natural variants are powerful tools to understand the molecular basis of GPCR function. Overall, this work contributes to our understanding of the function of melatonin receptors and highlights their importance in the regulation of the DA system and glucose homeostasis. Our results will open new, personalized therapeutic options for patient suffering from a defective DA system or T2D.

No description available.

Background: By optimizing a company's internal flows, several benefits, including reduction of waiting time and incidents, can be generated. A relevant starting point for the concept of lean production is the effort to reduce the amount of waste. A variant of an improvement tool is a so-called spaghetti diagram. This tool is considered optimal partly to reduce the amount of waste associated with the current layout and the flows that exist in the warehouse, and partly to get a picture of what safety looks like and how it could be optimized. This with regard to the way forklifts and people may relate to each other to avoid incidents, including collisions. Purpose: The purpose of the paper is, based on Volvo CE Braås logistics center, to study today's internal transport flows, its frequency and challenges associated with these in terms of safety and productivity. Furthermore, the purpose is to examine the corresponding transport flows in Volvo CE Braås logistics layout 2025, its frequency and how challenges related to safety and productivity at this stage can be addressed. Method: The study involves a qualitative approach where a case study has been conducted. Primary and secondary data has been collected in the form of both semi-structured and unstructured interviews. To create a well-founded analysis, pattern comparison has been chosen as the approach for the analysis method. This is because a theoretical basis is seen in relation to the basis that has been obtained from Volvo CE Braås, in order to obtain as well-founded a result as possible. Results: Regarding the frequency of transports in and out of the Volvo CE Braås logistics center in the current logistics layout, challenges have been identified in terms of safety and productivity. Challenges related to safety have turned out to be high frequency of internal transports, pedestrians and crossing flows. In terms of productivity, challenges also include the high frequency of internal transports and pedestrians moving in and out of the logistics center. Regarding future safety challenges in the 2025 logistics layout, they could be addressed by introducing one-way areas, optimizing the number of trucks, providing safety information and introducing automatic measurement of internal transports. In terms of productivity challenges, these could be addressed by introducing one-way areas, maintaining good communication, optimizing the number of trucks, providing safety information, offering training and introducing separate placement of AGVs and a separate loading area for trucks. / Bakgrund: Genom att optimera en verksamhets interna flöden kan flertalet fördelar, däribland reducering av väntetid och incidenter, genereras. En relevant utgångspunkt för begreppet lean production är strävan efter att reducera mängden slöserier. En variant av förbättringsverktyg är ett så kallat spagettidiagram. Detta verktyg anses vara optimalt dels för att reducera mängden slöserier med koppling till rådande layout och de flöden som existerar i lagret, dels för att få en bild av hur säkerheten ser ut och hur denna skulle kunna optimeras. Detta med avseende på vilket sätt truckar och människor får förhålla sig till varandra för att undvika incidenter, däribland kollisioner. Syfte: Syftet med uppsatsen är att, med utgångspunkt i Volvo CE Braås logistikcentrum, studera dagens interna transportflöden, dess frekvens samt utmaningar förknippade med dessa beträffande säkerhet och produktivitet. Vidare är syftet att undersöka motsvarande transportflöden i Volvo CE Braås logistiklayout 2025, dess frekvens samt hur utmaningar sett till säkerhet och produktivitet i detta skede kan angripas. Metod: Studien innefattas av ett kvalitativt tillvägagångssätt där en fallstudie har genomförts. För att skapa underlag till studien har primär- och sekundärdata samlats in i form av både semistrukturerade- och ostrukturerade intervjuer. För att skapa en  välgrundad analys har mönsterjämförelse valts som tillvägagångssätt för analysmetoden. Detta i och med att ett teoretiskt underlag ses i relation till det underlag som har erhållits från Volvo CE Braås, för att i sin tur erhålla ett så välgrundat resultat som möjligt. Resultat: Beträffande frekvensen av transporter inom och ut från Volvo CE Braås logistikcentrum i dagens logistiklayout, har utmaningar identifierats sett till säkerhet och produktivitet. Utmaningar med koppling till säkerhet har visat sig vara hög frekvens av de interna transporter som sker, fotgängare samt korsande flöden. Sett till produktivitet är utmaningar även här att det råder en hög frekvens av de interna transporterna samt att fotgängare rör sig inom och ut från logistikcentrum. Med avseende på framtida säkerhetsutmaningar i logistiklayouten 2025, skulle de kunna angripas genom att införa enkelriktade områden, optimera antalet truckar, ge säkerhetsinformation och införa automatisk mätning av interna transporter. Sett till produktivitetsutmaningar kan dessa angripas genom att även här införa enkelriktade områden, upprätthålla en god kommunikation, optimera antalet truckar, ge säkerhetsinformation, erbjuda utbildning och införa separat placering av AGV samt införa ett separat laddningsutrymme för truckar.