Denna rapport beskriver ett projekt som startats och utförts på Aspervall instrument AB. Projektet är en del i kursen examensarbete för högskoleingenjörer i maskinteknik, MSGC17, vid Karlstads universitet, fakulteten för hälsa, natur- och teknikvetenskap. Målet med arbetet var att presentera ett layoutförslag som kan användas för en planerad flytt av Aspervall Instruments verksamheten från befintliga lokaler till nya större lokaler. Rapporten består av flera olika delar. Den första delen består av en nulägesanalys där med hjälp av datainsamlingen (intervjuer, observationer och kundordrar), orsakverkandiagram och flödesschema en hel bild av företagets maskinpark har tagits fram för att kunna förstå problemen som finns i nuvarande layout. Analysen är byggd av underlag framtagna ur litteraturstudier inom tillhörande ämnen Följande del består av framtagningen av de sex olika layoutförslagen som skall lösa de problem framtagna ur nulägesanalysen. Mätning av de nya lokalerna, maskiner och dess tillhörande utrustning samt systematisk layout planering har använts som underlag för att kunna kartlägga en layout. Alla layoutförslag har framtagits med hjälp av Microsoft Visio och Smart Draw. Layoutförslagen 2,4 och 6 sållades bort ur de möjliga alternativen tillsammans med ledningen på Aspervall. De kvarstående förslagen 1,3 och 5 utvärderades sedan med hjälp av två olika metoder. Första metoden bestod av minskning i transporter och onödiga rörelser medans den andra utvärderade hur pass bra de olika förslagen kan lösa de nuvarande layoutproblemen som existerar. Layoutförslag 5 fick bäst resultat och anses därmed vara det förslag som lämpar sig bäst. Layoutförslag 5 minskade transporter och onödiga rörelser med 31% och fick högsta poäng i viktningsmatrisen. Förslaget består av bra verktyg och materialhantering med en kompakt maskinpark som uppfyller alla krav. Förslaget ger god möjlighet för arbetsrotation och kompetensöverföring inte bara inom en grupp men också mellan olika grupper vilket kan leda till ökande effektivitet och stark lagkänsla. Förslaget är skissat så att ut- och inflyttningen av de maskiner som skall bytas ut inte kommer att påverka dess produktion. För fortsatt arbete har olika förbättringsförslag presenterats samt har det även genomförts en utvärdering. Detta för att underlätta företagets beslut kring vart man skall börja arbetet i syn på enkelhet och effektivitet. Slutsatsen av utvärderingen visar att verktygshantering och regelbundna möten med personal är de två förbättringarna som är lättast att genomföra samt som ger störst effekt och nödvändigt resultat. / This report describes a project which is conceived at Aspervall Instruments AB. This project is a part of the course “degree project of Bachelor of Science in Mechanical Engineering”, MSGC17, at Karlstad University, the faculty of health, science and technology. The aim of the project was to present a layout proposal that could be used for a planned move of Aspervall Instruments operations from existing premises to new larger premises. The report consists of several different parts. The first part presents a current position analysis. With the help of the data collection (interviews, observations and study of customer orders), the cause-effect analysis and spaghetti diagram an entire picture of the company's machine park has been developed to understand the problems that exist in the current layout. The following part was the development of various layout proposals which solves the problems that were encountered under current position analysis. Measurement of machinery and their related equipments, measurement of the new premises and systematic layout planning have been used to map several layouts. All layout suggestions have been drafted using Microsoft Visio and Smart Draw. During the first screening together with the management, three layout suggestions, suggestion 2,4 and 6 were left out. Then the remaining layout suggestions 1,3 and 5 have been evaluated using two methods. The first method was about the number of reductions in transport and unnecessary movements, and the following one was about how well various proposals can solve the problems which exist within the current layout. Layout proposal 5 was the best result in the evaluation and is the most suitable proposal. The proposal reduces the unnecessary transport and movement with 31% and got highest points in the evaluation table. The proposal consists of comprehensive tools and material handling with a compact machine park that meets all requirements. The proposal provides a good opportunity for job rotation and transfer of skills not only in the group but also between different groups, which can lead to increased efficiency and can help to build a strong team spirit. The proposal is outlined so that moving of the machines which are planned to be replaced / purchased in the near future will not affect production. For continuing work, various improvement proposals have been presented as well as an evaluation has also been conducted to facilitate the management in their decision regarding what to begin with, in terms of efficiency and easy to implement. According to the evaluation tool handling and regular meetings with the staff are the two easy-to-implement enhancements and can provide effective and responsive results.

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No. of bitstreams: 1 regatieri_ic_dr_jabo.pdf: 1026482 bytes, checksum: 93ce299c664eb44473c4cdf6c6496fb4 (MD5) Previous issue date: 2016-10-19 / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / O transportador de monocarboxilato isoforma 1 (MCT1), presente na membrana das hemácias, e sua proteína auxiliar CD147 têm como função transportar H+ e lactato do plasma para dentro das hemácias, mantendo assim, a homeostase ácido-base e retardando a acidose sistêmica e fadiga muscular. Dessa forma, o objetivo desse estudo foi comparar as quantidades das proteínas MCT1 e CD147 em hemácias de cavalos Árabes e Quartos de Milha com diferentes níveis de desempenho atlético. Além disso, objetivou-se buscar por polimorfismos para os genes MCT1, CD147, DMRT3 e PDK4, a fim de checar associações entre os polimorfismos e o desempenho nas raças. Cavalos Árabes e Quartos de Milha foram divididos em dois grupos de acordo com o desempenho em provas de enduro e provas de corridas, respectivamente. A quantidade de MCT1 e CD147 na membrana plasmática das hemácias foi determinada por western blotting com unidades arbitrárias de densidade óptica (OD) e anticorpos reagentes à espécie humana anti-MCT1 e anti-CD147. Os dados para as quantidades de proteínas foram analisados pelo PROC MIXED do SAS. O modelo incluiu a idade como covariável e os efeitos fixos de sexo, raça e grupo de desempenho dentro de raça. As correlações foram analisadas pelo teste de Pearson pelo procedimento PROC CORR. P-valores <0,01 foram considerados estatisticamente significantes. Os polimorfismos dos genes foram analisados por sequenciamento (MCT1 e CD147), PCR-RFLP (DMRT3) e ARMS-PCR (PDK4). Os pacotes estatísticos Genetics, Lattice e GenABEL foram utilizados para comparar as frequências dos grupos de desempenho no software R, com o teste exato de Fisher a 5% de significância. As proteínas MCT1 e CD147 foram encontradas nas hemácias de todos os animais. A quantidade de MCT1 foi significativamente (p<0,0001) maior em Quartos de Milha (2,99 ± 0,35 OD) do que em Árabes (1,04 ± 0,08 OD). Quartos de Milha (3,23 ± 0,38 OD) também apresentaram maior conteúdo de CD147 do que Árabes (0,88 ± 0,06 OD). Não houve diferença estatística nas quantidades de proteínas para os grupos de desempenho de ambas as raças. Correlação positiva foi encontrada entre as quantidades de MCT1 e CD147 (r=0,95; p<0,0001). O Alelo A dos polimorfismos Lys457Gln:1573A>C do gene MCT1 e Ile51Val:168A>G do gene CD147 estavam fixados em ambas as raças. Um novo polimorfismo (AY457175.1:c1498G>A) foi encontrado na sequência do gene MCT1. Para o DMRT3, todos os animais apresentaram o alelo C fixado para o polimorfismo. Árabes mostraram maior frequência para o alelo G do que Quartos de Milha (p<0,01) para o polimorfismo no gene PDK4. Entretanto, não houve diferença entre os grupos de desempenho para as duas raças. Dessa forma, conclui-se que Quartos de Milha têm maiores quantidades de MCT1 e CD147 do que Árabes. Não foi possível determinar a influência dos polimorfismos nos genes MCT1, CD147 e DMRT3 no desempenho atlético das duas raças visto que seus alelos estavam fixados. Além disso, houve diferença significativa nas frequências do polimorfismo no gene PDK4 entre Árabes e Quartos de Milha, mas não houve diferença entre os grupos de desempenho. / Monocarboxylate transporter isoform 1 (MCT1), present in the red blood cell membranes and its ancillary protein CD147 have as function transport H+ and lactate ions from the plasma into the red blood cells, thereby maintaining acid/base homeostasis and retarding systemic acidosis and muscular fatigue. Thereby, the aim of this study was to compare the amount of MCT1 and CD147 proteins in the red blood cells of Arabian and Quarter Horses with different levels of athletic ability. Furthermore, we investigated polymorphisms for MCT1, CD147, DMRT3, and PDK4 genes in Arabian and Quarter Horses in order to check associations between the polymorphisms and the performance in these breeds. Arabian horses were divided into two groups according to their performance in endurance competition and Quarter Horses were separated by its performance in races, determined by Speed Index. The amount of MCT1 and CD147 proteins in the plasma membrane of red blood cells was determined by western blotting analysis with arbitrary optical density units (OD), using a human specific anti-MCT1 and anti- CD147 antibody. Data for the amounts of proteins were analyzed using the PROC MIXED procedure of SAS software. The model for the analysis included the effects of sex, breed and performance group within breed as fixed effect and age as covariate. The correlations were analyzed by Pearson correlation test using the PROC CORR procedure of SAS software. P values <0.01 were considered statistically significant. Polymorphisms of the genes were analyzed by sequencing (MCT1 and CD147), PCR-RFLP (DMRT3) and ARMS-PCR (PDK4) techniques. The statistical packages Genetics, Lattice and GenABEL were used to compare the frequencies of the groups using the software R, with the Fisher's exact test being performed with significance level of 5%. MCT1 and CD147 proteins were found in the red blood cell membranes of all studied animals. The amount of MCT1 was significantly (p<0.0001) higher in Quarter Horses (2.99 ± 0.35 OD) than in Arabians (1.04 ± 0.08 OD). Quarter Horses (3.23 ± 0.38 OD) also showed bigger contents of CD147 than Arabians (0.88 ± 0.06 OD). There was not statistical difference in the amounts of MCT1 and CD147 between the performance groups of both breeds. Positive correlation was found between the amounts of MCT1 and CD147 (r=0.95; p<0.0001). The A allele from the polymorphisms Lys457Gln:1573A>C of MCT1 and Ile51Val:168A>G of CD147 gene, were fixed in both breeds. A new polymorphism (AY457175.1:c1498G>A) was found in the MCT1 gene sequence. For DMRT3 mutation, all the animals shown to have the C allele fixed for the polymorphism. Arabians showed significant greater frequency of the G allele than Quarter Horses (p<0.01) for the PDK4 polymorphism. However, there was not difference between the groups of performance for both breeds. In summary, it follows that the Quarter Horses have greater amount of MCT1 and CD147 proteins than Arabian. It was not possible to determine the influence of polymorphisms in MCT1, CD147 and DMRT3 genes in the athletic performance of these breeds since they had alleles fixed. There was a significant difference in the frequencies of the PDK4 polymorphism between Arabians and Quarter Horses, but there was not difference between the performance groups. / FAPESP: 2012/24193-0 / FAPESP: 2012/20697-9

The aim of this work was to characterise the influence of adenosine on imaginal disc cell line Cl8+ of Drosophila. I prepared stable cell lines with the overexpression or RNA interference of genes coding adenosine receptor AdoR (CG9753) and adenosine transporter DmENT2 (CG11045) in D. melanogaster. These cell lines were subsequently used to test their response to extracellular adenosine signal by the measurement of cell viability and level of second messengers cAMP and Ca2+ in Cl8+ cells.

abstract: Lignocellulosic biomass represents a renewable domestic feedstock that can support large-scale biochemical production processes for fuels and specialty chemicals. However, cost-effective conversion of lignocellulosic sugars into valuable chemicals by microorganisms still remains a challenge. Biomass recalcitrance to saccharification, microbial substrate utilization, bioproduct titer toxicity, and toxic chemicals associated with chemical pretreatments are at the center of the bottlenecks limiting further commercialization of lignocellulose conversion. Genetic and metabolic engineering has allowed researchers to manipulate microorganisms to overcome some of these challenges, but new innovative approaches are needed to make the process more commercially viable. Transport proteins represent an underexplored target in genetic engineering that can potentially help to control the input of lignocellulosic substrate and output of products/toxins in microbial biocatalysts. In this work, I characterize and explore the use of transport systems to increase substrate utilization, conserve energy, increase tolerance, and enhance biocatalyst performance. / Dissertation/Thesis / Doctoral Dissertation Biological Design 2018

A depressão pós-parto (DPP) é um importante problema de saúde pública podendo provocar uma ruptura do vínculo entre a mãe e o bebê e até estar associada com respostas trágicas, como suicídio materno e infanticídio. A DPP é multifatorial e o seu surgimento pode ser favorecido por componentes hormonais, genéticos e ambientais. O ciclo gravídico-puerperal é considerado um período de risco, pois algumas mulheres possuem uma sensibilidade particular as alterações hormonais. O risco de DPP é aumentado em mulheres que possuem histórico de depressão na família, logo, um componente genético determina maior suscetibilidade. Segundo o DMS-IV, existe uma relação entre a sintomatologia depressiva e as alterações na concentração cerebral de neurotransmissores, com destaque para serotonina. O transportador de serotonina (SERT) controla a intensidade e duração da re-captação da serotonina nas sinapses serotonérgicas. Diversos trabalhos associam os polimorfismos do SERT com transtornos mentais, como unipolar, bipolar, depressão e esquizofrenia. Nosso objetivo foi analisar as concentrações salivares de cortisol (CORT), as freqüências alélicas e genotípicas dos polimorfismos 5-HTTVNTR e 5- HTTLPR no gene SLC6A4 entre mulheres que desenvolveram ou não DPP. A amostra foi constituída por 128 mulheres brancas da cidade de Pelotas/RS, triadas em ambulatórios do SUS. A avaliação diagnóstica foi realizada através de entrevista psiquiátrica e diagnóstica usando como instrumento o Beck Depression Inventory entre 30 a 45 dias após o nascimento das crianças. A coleta de material biológico (leucócitos e saliva) foi realizada no turno da manhã, respeitando o período de duas horas de jejum. A região promotora do gene contendo o polimorfismo 5-HTTLPR (inserção/deleção) e a região do segundo íntron contendo o polimorfismo 5- HTTVNTR (repetições em tandem) foram amplificadas através da reação em cadeia da polimerase. A dosagem do CORT foi realizada a partir da saliva por técnica de ELISA utilizando kit específico. A mediana e o intervalo interquartil das concentrações salivares do CORT entre os portadores dos diferentes genótipos foram comparados entre os grupos estudados usando o teste de Kruskal-Wallis e Mann-Whitney. A comparação das freqüências alélicas e genotípicas dos polimorfismos estudados entre as mulheres que apresentarem ou não DPP foram feitas pelo teste do Qui-quadrado com correção de Yates (p£ 0,05). A análise da distribuição das freqüências genotípicas dos polimorfismos 5-HTTLPR e 5- HTTVNTR do SERT permitiu verificar que a população está sob Equilíbrio Hardy– Weinberg. Quando os polimorfismos foram analisados isoladamente, não foi observada associação entre os polimorfismos 5-HTTLPR (p=0,48) e 5-HTTVNTR (p=0,77) e o diagnóstico para DPP. Porém, a análise combinada dos haplótipos dos polimorfismos 5-HTTLPR e 5-HTTVNTR demonstraram que mulheres portadoras do diplótipo L-12/L-12 apresentaram escores menores de sintomas depressivos (mediana: 0,5; intervalo inter-quartil: 0,00-4,00, p=0,04) quando comparadas com mulheres portadoras de outros diplótipos (mediana: 4,0; intervalo inter-quartil: 1,00- 10,00). O polimorfismo 5-HTTVNTR foi associado com as concentrações salivares de CORT (p=0,03), já o polimorfismo 5-HTTLPR não foi associado (p=0,41). Nossos achados são inovadores, visto que até a presente data a associação dos genótipos 5-HTTLPR e 5-HTTVNTR com DPP e concentrações salivares de CORT ainda não haviam sido investigados. / The postpartum depression (PPD) is an important public health problem that may cause a rupture of the bond between the mother and the baby and may even be associated with tragic responses such as maternal suicide and infanticide. The DPP is multifactorial and its appearance can be favored by hormonal components, genetic and environmental factors. The pregnancy and childbirth is considered a risk period, because some women have a particular sensitivity to hormonal changes. The rate of DPP is increased in women who have a record of depression in the family, so a genetic component determines higher susceptibility. According to the DSM-IV, there is a relationship between depressive symptoms and brain concentration changes of neurotransmitters, particularly serotonin. The serotonin transporter (SERT) controls the intensity and duration of re-uptake of serotonin in serotonergic synapses. Several studies linking polymorphisms of SERT with mental disorders such as unipolar, bipolar, depression, and schizophrenia. Our objective was to analyze the concentrations of salivary cortisol (CORT), the allele and genotype frequencies of polymorphisms 5-HTTLPR and 5-HTTVNTR SLC6A4 gene in women who developed or not DPP. The sample consisted of 128 white women from Pelotas, RS, sorted out from public health clinics. The diagnostic evaluation was conducted through interviews and psychiatric diagnostic instrument as using the Beck Depression Inventory among 30 to 45 days after the birth of children. The collection of biological materials (leukocytes and saliva) was performed in the morning, observing the twohour period of fasting. The promoter region of the gene containing the 5-HTTLPR polymorphism (insertion/deletion) and the region containing the second intron polymorphism 5-HTTVNTR (tandem repeats) were amplified by polymerase chain reaction. The dose of CORT was performed from the saliva by ELISA using the specific kit. The median and interquartile interval of salivary concentrations of CORT among patients of different genotypes were compared between groups using the Kruskal-Wallis and Mann-Whitney. The comparison of allele and genotype frequencies of polymorphisms among women who developed or not DPP were made by chi-square test with Yates correction (p <0.05). The analysis of the distribution of genotype frequencies of polymorphisms 5-HTTLPR and 5-HTTVNTR SERT showed that the population is under Hardy-Weinberg Equilibrium. When the polymorphisms were analyzed alone, no association was observed between the 5-HTTLPR (p=0.48) and 5-HTTVNTR (p=0.77) polymorphisms and the PPD diagnosis. But, the information from these analyses combined with information regarding the haplotypes of the 5-HTTLPR and 5-HTTVNTR polymorphisms demonstrated that women carriers of diplotype L-12/L-12 have a lower depression symptoms score (median: 0.5; interquartile range: 0.00-4.00; p=0.04) than women with other diplotypes (median: 4.0; inter-quartile range: 1.00-10.00). The 5-HTTVNTR polymorphism was associated with the salivary concentrations of CORT (p=0.03), whereas the 5-HTTLPR polymorphism was not associated (p=0.41). Our findings are innovative since the association of 5- HTTLPR genotypes and 5-HTTVNTR with DPP and salivary concentrations of CORT had not been investigated before.

No description available.

Linköpings kommun ska införa samordnad varudistribution för transporter till kommunens verksamheter. I nuläget går kommunens transporter direkt från leverantörerna till kommunens verksamheter. Med samordnad varudistribution kommer kommunens gods att anlända till en samlastningscentral där godset samlastas och körs ut till de kommunala verksamheterna. Förhoppningen är att detta ska ge en minskning av koldioxidutsläpp, partikelutsläpp, godshantering vid verksamheterna och minskad tung trafik vid kommunens verksamheter. För att kunna utvärdera resultatet av samordnad varudistribution krävs att transportpåverkan innan ett införande kan mätas och jämföras med dess påverkan efter ett införande. För att dessa mätningar ska kunna jämföras krävs att mätningarna genomförs på samma sätt före och efter införandet. Det finns en osäkerhet kring hur detta skulle kunna mätas. Syftet med studien är att undersöka vilka nyckeltal som är intressanta att mäta före och efter ett införande av samordnad varudistribution. Många städer har svårigheter gällande trafikstockningar och miljöfarliga utsläpp som leder till negativa effekter för både människor och miljön. Godstrafiken behövs för att transportera gods från fabriker till slutkunder men påverkar både växthuseffekten och stadsmiljö genom miljöfarliga utsläpp, buller och trafikolyckor. En samlastningscentral minskar bland annat på de negativa externa effekterna av godstransporter i städerna. Intervjuer har genomförts för att undersöka hur andra verksamheter som infört samordnad varudistribution gått tillväga och vad de fått för resultat. Det framkom att det var svårigheter med att få fram transportdata före införandet och att transportsituationen är väldigt komplex. Genom att verksamheterna har mer information om sina godstransporter underlättar det för dem att planera och styra över dem. En ökad positiv miljöeffekt för staden skulle kunna nås om fler verksamheter använde sig av samlastning.

It can be difficult to choose the right NoSQL DBMS, and some systems lack sufficient research and evaluation. There are also tools for moving and transforming data between DBMS' in order to combine or use different systems for different use cases. We have described a use case, based on requirements related to the quality attributes Consistency, Scalability, and Performance. For the Performance attribute, focus is fast insertions and full-text search queries on a large dataset of forum posts. The evaluation was performed on two NoSQL DBMS' and two tools for transforming data between them. The DBMS' are MongoDB and Elasticsearch, and the transformation tools are NotaQL and Compose's Transporter. The purpose is to evaluate three different NoSQL systems, pure MongoDB, pure Elasticsearch and a combination of the two. The results show that MongoDB is faster when performing simple full-text search queries, but otherwise slower. This means that Elasticsearch is the primary choice regarding insertion and complex full-text search query performance. MongoDB is however regarded as a more stable and well-tested system. When it comes to scalability, MongoDB is better suited for a system where the dataset increases over time due to its simple addition of more shards. While Elasticsearch is better for a system which starts off with a large amount of data since it has faster insertion speeds and a more effective process for data distribution among existing shards. In general NotaQL is not as fast as Transporter, but can handle aggregations and nested fields which Transporter does not support. A combined system using MongoDB as primary data store and Elasticsearch as secondary data store could be used to achieve fast full-text search queries for all types of expressions, simple and complex.

No description available.

Philosophiae Doctor - PhD / Solute carrier transporters belonging to the major facilitator family of membrane transporter are increasingly being recognized as a possible mechanism to explain inter-individual variation in drug efficacy and response. Genetic factors are estimated to be responsible for approximately 15-30% of inter-individual variation in drug disposition and response. The aims of this study were to determine the minor allele frequencies of 78 previously identified single nucleotide polymorphisms in the pharmacogenomically relevant SLC22A1-3 and SLCO1B1 genes in the Admixed population of South Africa. Thereafter, to determine whether allele and genotype frequencies for these SNP were different from that reported for other African, Caucasian, and Asian populations. The inferred haplotypes from the genetic information possessed the potential to subsequently be used in future to design and interpret results of pharmacogenomic association studies involving these genes and their substrate drugs. Furthermore, to determine whether the Cape Admixed population harbour novel SNPs in the proximal promoter regions of SLC22A1- 3 and SLCO1B1-3 genes, that encodes hOCT1-3 and hOATP1 and hOATP3, respectively. SNaPshot™ multiplex single base mini-sequencing systems were developed and optimized for each of SLC22A1, SLC22A2, SLC22A3, and SLCO1B1 genes covering the previously identified 78 SNPs. These systems were then used to genotype the alleles of 130 healthy Cape Admixed subjects residing in Cape Town, South Africa. In addition, the proximal promoter regions of the SLC22A1-3 and SLCO1B1-3 genes of 96 of the participants were screened for novel SNPs by direct sequencing. The Cape Admixed subjects investigated displayed a lack of variation and were monomorphic for 78% of the SNPs screened. None of the SLC22A3 SNPs investigated was observed in this study. Sequencing of the proximal promoter regions of the SLC22 and SLCO genes did not reveal any novel SNPs in the 96 Cape Admixed subjects that were screened. This study highlights the fact that African populations do not have the same allele frequencies for SNPs in harmacogenomically relevant genes. Furthermore, the Cape Admixed and other African populations do not share all reduced-function variants of the SLC22A1-3 and SLCO1B1-3 genes with Caucasian and Asian populations. In addition, previously identified novel regulatory variants in SLC22A2 did not exhibit a significant effect on the ability of the promoter to drive transcription. However, it must be noted that these results were observed at 95% confidence interval, and that a 99% confidence interval the significance may increase theoretically. Additionally, it should be noted that more intensive studies are required to determine the potential effect these novel variants may well cause. This study lays the foundation for the design and interpretation of future pharmacogenomic association studies between the variant alleles of the SLC22A and SLCO genes in the Cape Admixed population, as well as optimizations for future expression, and more importantly, drug transport assays with respect to drug disposition and efficacy. / National Research Foundation (NRF) and the Medical Research Council (MRC)