SMART METERS AND DEMAND SIDE MANAGEMENT IN SMART GRIDS – EXPLORING CHALLENGES AND OUTLINING FUTURE RESEARCH DIRECTIONS

This research in progress paper explores smart meters and demand side management (DSM) challenges and how this is perceived by suppliers of smart grids. It builds on semi-structured interviews and a literature review showing that smart meters are a highly important, relevant, and interesting research topic. We identify a need to include knowledge on how to develop smart meter technology further as well as how to increase both supplier and energy user engagement and involvement in development of smart meters technology. Our research shows that there exist gaps between: policies, goals and expectations on one side and implementation and use of smart meters on the other side. Based on initial results we conclude that there is a need to explore DSM and smart meter technology further and to learn from a social-technical IS perspective to overcome a one-sided perspective, or even deterministic view, on technology

A novel RAD21 p.(Gln592del) variant expands the clinical description of Cornelia de Lange syndrome type 4 – Review of the literature.

Cornelia de Lange syndrome (CdLS) is a heterogeneous developmental disorder where 70% of clinically diagnosed patients harbor a mutation in one of five CdLS associated cohesin proteins. Around 500 mutations have been identified to cause CdLS, however only eight different alterations are identified in RAD21, encoding the RAD21 cohesin protein that constitute the link between SMC1A and SMC3 within the cohesin ring. We report a 15- month-old boy presenting with developmental delay, distinct CdLS facial features, gastrointestinal reflux in early infancy, testis retention fetal pads and diaphragmatic hernia. Exome sequencing revealed a novel RAD21 variant, c.1774_1776del; p.(Gln592del), suggestive of CdLS type 4. Segregation analysis of the two healthy parents confirmed the variant as de novo and bioinformatic analysis predicted the variant as disease-causing. Functional assessment by in silico structural model predicted that the p.Gln592del variant results in a discontinued contact between RAD21-Lys591 and the SMC1A residues Glu1191 and Glu1192, causing changes in the RAD21-SMC1A interface. In conclusion, we report a novel RAD21 p.(Glu592del) variant that expands the clinical description of CdLS type 4 and validate the pathogenicity of the variant by in silico structural modeling that displayed disturbed RAD21-SMC1A interface.pre-print2,82 M

A synonymous germline variant in a gene encoding a cell adhesion molecule is associated with cutaneous mast cell tumour development in Labrador and Golden Retrievers

Mast cell tumours are the most common type of skin cancer in dogs, representing a significant concern in canine health. The molecular pathogenesis is largely unknown, but breed-predisposition for mast cell tumour development suggests the involvement of inherited genetic risk factors in some breeds. In this study, we aimed to identify germline risk factors associated with the development of mast cell tumours in Labrador Retrievers, a breed with an elevated risk of mast cell tumour development. Using a methodological approach that combined a genome-wide association study, targeted next generation sequencing, and TaqMan genotyping, we identified a synonymous variant in the DSCAM gene on canine chromosome 31 that is associated with mast cell tumours in Labrador Retrievers. DSCAM encodes a cell-adhesion molecule. We showed that the variant has no effect on the DSCAM mRNA level but is associated with a significant reduction in the level of the DSCAM protein, suggesting that the variant affects the dynamics of DSCAM mRNA translation. Furthermore, we showed that the variant is also associated with mast cell tumours in Golden Retrievers, a breed that is closely related to Labrador Retrievers and that also has a predilection for mast cell tumour development. The variant is common in both Labradors and Golden Retrievers and consequently is likely to be a significant genetic contributor to the increased susceptibility of both breeds to develop mast cell tumours. The results presented here not only represent an important contribution to the understanding of mast cell tumour development in dogs, as they highlight the role of cell adhesion in mast cell tumour tumourigenesis, but they also emphasise the potential importance of the effects of synonymous variants in complex diseases such as cancer. Author summary The combination of various genetic and environmental risk factors makes the understanding of the molecular circuitry behind complex diseases, like cancer, a major challenge. The homogeneous nature of pedigree dog breed genomes makes these dogs ideal for the identification of both simple disease-causing genetic variants and genetic risk factors for complex diseases. Mast cell tumours are the most common type of canine skin cancer, and one of the most common cancers affecting dogs of most breeds. Several breeds, including Labrador Retrievers (which represent one of the most popular dog breeds), have an elevated risk of mast cell tumour development. Here, by using a methodological approach that combined different techniques, we identified a common inherited synonymous variant, that predisposes Labrador Retrievers to mast cell tumour development. Interestingly, we showed that this variant, despite its synonymous nature, appears to have an effect on translation dynamics as it is associated with reduced levels of DSCAM, a cell adhesion molecule. The results presented here reveal dysregulation of cell adhesion to be an important factor in mast cell tumour pathogenesis, and also highlight the important role that synonymous variants can play in complex diseases

Genome-Wide Association Study of Golden Retrievers Identifies Germ-Line Risk Factors Predisposing to Mast Cell Tumours

Canine mast cell tumours (CMCT) are one of the most common skin tumours in dogs with a major impact on canine health. Certain breeds have a higher risk of developing mast cell tumours, suggesting that underlying predisposing germ-line genetic factors play a role in the development of this disease. The genetic risk factors are largely unknown, although somatic mutations in the oncogene C-KIT have been detected in a proportion of CMCT, making CMCT a comparative model for mastocytosis in humans where C-KIT mutations are frequent. We have performed a genome wide association study in golden retrievers from two continents and identified separate regions in the genome associated with risk of CMCT in the two populations. Sequence capture of associated regions and subsequent fine mapping in a larger cohort of dogs identified a SNP associated with development of CMCT in the GNAI2 gene (p = 2.2x10(-16)), introducing an alternative splice form of this gene resulting in a truncated protein. In addition, disease associated haplotypes harbouring the hyaluronidase genes HYAL1, HYAL2 and HYAL3 on cfa20 and HYAL4, SPAM1 and HYALP1 on cfa14 were identified as separate risk factors in European and US golden retrievers, respectively, suggesting that turnover of hyaluronan plays an important role in the development of CMCT

Identification of Genomic Regions Associated with Phenotypic Variation between Dog Breeds using Selection Mapping

Peer reviewe

KUNDERNA I FOKUS - kulturens inverkan på kundnärhet, kundtillfredsställelse och företagets representanter : OY KWH Plast AB

Oy KWH Plast Ab, affärsenheten PAC i Jakobstad fungerade som uppdragsgivare för vårt arbete och vår undersökning. Oy KWH Plast Ab består av tre affärsenheter: Stationery, PAC och Label. Affärsenheten PAC tillverkar förpackningsfilmer för livsmedelsindustrin och formsprutade förpackningar. I den empiriska delen av examensarbetet behandlade vi kundnärhet, kundtillfredsställelse, företagets globala representanter och interkulturell kommunikation. I kapitlet företagets globala representanter och interkulturell kommunikation avhandlade vi vad interkulturell kommunikation innebär, olika kulturer och kulturskillnader samt hur dessa påverkar företagets globala representanter. Kundnärhet behandlar segmentering, kundrelationer och kundlönsamhet. Kundtillfredsställelse bearbetar kvalitet, pris, lojalitet, reklamationer, nöjda och missnöjda kunder samt kundservice och kundvärdskap. I den praktiska delen examensarbetet gjorde vi en kundtillfredsställelseundersökning bland affärsenheten PAC:s kunder. Undersökningen gjordes som en webbenkät och sändes till följande länder: Finland, Sverige, Danmark, Norge, Tyskland, Schweiz, Österrike, Frankrike, England, Irland, Spanien, Italien och Benelux. Genom vår undersökning fick vi kännedom om att affärsenheten PAC:s kunder anser att företaget har högt prissatta produkter, men en god produktkvalitet och produktutveckling samt ett gott produktutbud. Överlag ansåg kunderna att enheten som helhet är till belåtenhet, särskilt uppskattades kundservicen.KWH Plast Ltd, business unit PAC in Pietarsaari was our assigner for our thesis and examination. KWH Plast Ltd consists of three business units: Stationery, PAC and Label. Business unit PAC manufactures packaging films and injection moulded packaging. In the empirical part we have discussed customer nearness, customer satisfaction, the company’s global representatives and intercultural communication. In the chapter the company’s global representatives and intercultural communication we have considered what intercultural communication means, different cultures and culturaldifferences and how these affect the company’s global representatives. Customer nearness deals with issues such as segmentation, customer relationship and customer profitability. Customer satisfaction discusses quality, price, loyalty, reclamations, satisfied and dissatisfied customer and customer service. In the practical part we have done a customer satisfaction survey among business unit PAC’s customers. The survey was implemented as a websurvey and sent to the following countries: Finland, Sweden, Denmark, Norway, Germany, Switzerland, Austria, France, England, Ireland, Spain, Italy and Benelux. Throughout our survey we became aware about business unit PAC’s customers opinion about the company’s highly priced products, but a good product quality, product development and product range. For the most part the customers thought that the unit as a whole was satisfying, especially customer service was appreciated

Identification of Candidate Genes in Four Human Disorders

The aim of this thesis has been to identify genes and gene regions underlying four different disorders. In papers I-IV, positional cloning methods, such as linkage, association and haplotype analysis have been used for the identification of genomic regions associated with the ichthyosis prematurity syndrome (IPS), adult-onset autosomal dominant leukodystrophy (ADLD) and Kostmann disease. IPS is a rare autosomal recessive skin disorder, which includes a premature birth of the affected child. We mapped the IPS locus to a region on chromosome 9q34, and within this region a haplotype is shared by IPS patients, which suggests a strong founder effect. The haplotype spans 76 kb, which includes four known genes. No sequence or mRNA expression alterations could be detected for the four genes in IPS patients. A candidate region for an adult-onset leukodystrophy (ADLD) on chromosome 5 was investigated in a large Swedish family with ADLD. A significant multipoint LOD score of 9.45 was obtained for markers in the chromosome 5 region and fine-mapping of recombination events restricts a candidate gene region to 1.5 Mb. Kostmann disease is an autosomal recessive form of severe congenital neutropenia. We have identified a 1.2 Mb region on chromosome 1q22 associated with the disease in the original Kostmann family. The region contains 37 genes. In paper V, cDNA microarrays were used to asses the mRNA levels of 7,700 genes in lymphoblastoid cell lines derived from autistic and control samples. The SEMA5A gene, which is involved in axonal guidance, was found downregulated in the cells derived from autistic individuals, and this was confirmed by quantitative PCR. In summary, candidate genes or gene regions have been identified for all four disorders and further studies are needed to confirm their roles in the pathogenesis of the disorders

Identification of Candidate Genes in Four Human Disorders

The aim of this thesis has been to identify genes and gene regions underlying four different disorders. In papers I-IV, positional cloning methods, such as linkage, association and haplotype analysis have been used for the identification of genomic regions associated with the ichthyosis prematurity syndrome (IPS), adult-onset autosomal dominant leukodystrophy (ADLD) and Kostmann disease. IPS is a rare autosomal recessive skin disorder, which includes a premature birth of the affected child. We mapped the IPS locus to a region on chromosome 9q34, and within this region a haplotype is shared by IPS patients, which suggests a strong founder effect. The haplotype spans 76 kb, which includes four known genes. No sequence or mRNA expression alterations could be detected for the four genes in IPS patients. A candidate region for an adult-onset leukodystrophy (ADLD) on chromosome 5 was investigated in a large Swedish family with ADLD. A significant multipoint LOD score of 9.45 was obtained for markers in the chromosome 5 region and fine-mapping of recombination events restricts a candidate gene region to 1.5 Mb. Kostmann disease is an autosomal recessive form of severe congenital neutropenia. We have identified a 1.2 Mb region on chromosome 1q22 associated with the disease in the original Kostmann family. The region contains 37 genes. In paper V, cDNA microarrays were used to asses the mRNA levels of 7,700 genes in lymphoblastoid cell lines derived from autistic and control samples. The SEMA5A gene, which is involved in axonal guidance, was found downregulated in the cells derived from autistic individuals, and this was confirmed by quantitative PCR. In summary, candidate genes or gene regions have been identified for all four disorders and further studies are needed to confirm their roles in the pathogenesis of the disorders

Identification of Candidate Genes in Four Human Disorders

The aim of this thesis has been to identify genes and gene regions underlying four different disorders. In papers I-IV, positional cloning methods, such as linkage, association and haplotype analysis have been used for the identification of genomic regions associated with the ichthyosis prematurity syndrome (IPS), adult-onset autosomal dominant leukodystrophy (ADLD) and Kostmann disease. IPS is a rare autosomal recessive skin disorder, which includes a premature birth of the affected child. We mapped the IPS locus to a region on chromosome 9q34, and within this region a haplotype is shared by IPS patients, which suggests a strong founder effect. The haplotype spans 76 kb, which includes four known genes. No sequence or mRNA expression alterations could be detected for the four genes in IPS patients. A candidate region for an adult-onset leukodystrophy (ADLD) on chromosome 5 was investigated in a large Swedish family with ADLD. A significant multipoint LOD score of 9.45 was obtained for markers in the chromosome 5 region and fine-mapping of recombination events restricts a candidate gene region to 1.5 Mb. Kostmann disease is an autosomal recessive form of severe congenital neutropenia. We have identified a 1.2 Mb region on chromosome 1q22 associated with the disease in the original Kostmann family. The region contains 37 genes. In paper V, cDNA microarrays were used to asses the mRNA levels of 7,700 genes in lymphoblastoid cell lines derived from autistic and control samples. The SEMA5A gene, which is involved in axonal guidance, was found downregulated in the cells derived from autistic individuals, and this was confirmed by quantitative PCR. In summary, candidate genes or gene regions have been identified for all four disorders and further studies are needed to confirm their roles in the pathogenesis of the disorders

Socialarbetares förhållningssätt gentemot sina klienter i utredande arbete

I socialt arbete finns det flertalet lagar, riktlinjer och regler som påverkar socialarbetares förhållningssätt gentemot deras klienter. Inom kommunalt utredningsarbete representerar socialarbetarna en myndighet och deras arbete genomsyras av en maktobalans som existerar mellan dem och klienterna. Maktobalansen uppenbaras av att socialarbetaren har lagar som ger dem maktbefogenheter att ingripa i människors liv och bestämma över beslut som rör deras klienter oavsett om klienterna själva vill det eller inte. Utifrån denna komplexa relation har studiens syfte växt fram; att undersöka hur socialarbetare beskriver sitt förhållningssätt gentemot sina klienter. En kvalitativ metod i form av fem semistrukturerade intervjuer har används för att uppfylla studiens syfte. På utredningsenheten vuxen i Örebro kommun bemöter socialarbetarna både unga vuxna och vuxna personer. Eftersom unga vuxna personer nyligen enligt lag har blivit ansedda som vuxna, innebär det att de får ett större ansvar för sitt eget liv. Med anledning av detta har studien även i syfte att undersöka om det går att uttyda skillnader i socialarbetares beskrivningar av deras förhållningssätt beroende på om klinten är ung vuxen eller vuxen och i så fall vilka. Enligt vår tolkning har resultatet för studien påvisat att socialarbetarna har ett etiskt och professionellt förhållningssätt gentemot sina klienter. Vi anser att socialarbetarna har ett annat tänk gentemot klienter som är unga vuxna men vi menar att förhållningssättet är detsamma som mot vuxna och påverkar inte etiken i det sociala arbetet.In social work there are a lot of rules, guidelines and laws that influence the social workers relationship with their clients. Within the local authority the social workers represent an agen-cy witch execute investigative work. This work is imbued with a power of imbalance between the social workers and their clients. The social workers have the authority by law to involve in other people’s lives and make decisions that affect their clients, even if the clients want it or not. Based on this complex relationship the purpose of the study has developed; to examine how social workers describe their attitudes toward their clients. A qualitative method with five semi-structured interviews was used to fulfill the purpose of the study. In the adult unit of investigation in the local authority of Örebro, Sweden, the social workers meet both young adult and adult clients. Since young adults recently by law are considered as adults it means taking a more substantial responsibility for their own lives. Regarding this, the study also has the purpose to examine if differences can be interpreted from the social workers explanations about their attitude toward their client, depending whether if the client are young adult or adult. According to our interpretation, the results of the study revealed that social workers have an ethical and professional attitude toward their clients. According to us, the social workers have a different mindset towards clients whom are young adults but we mean that their attitude is the same as toward the adults and do not have an effect on the ethnics in the social work