Olemassa olevan tuoteperheen modularisointi

This Master of Science Thesis was made for Cargotec Oy. Variability of products and the different customer needs have increased the amount of part numbers that have to be maintained. This thesis seeks to find a solution for the problem. The aim of the thesis is to demonstrate how an existing product family can be modularized. Modularity has been studied a great deal in recent years and a number of different methods have been developed for modularizing product structures. This thesis introduc-es the Design Structure Matrix, Function Heuristics and Modular Function Deployment methods. The study of these methods, however, indicates that none of these are suitable as such for the modularization of an existing product family. The Brownfield Process is studied in more detail, because it is developed specifically for the modularization of existing product families. The thesis works as an instruction manual for the case company, in which modulariza-tion is explained and the different steps of the Brownfield Process are clarified in detail. The Brownfield Process was applied to the case company’s products and a proposal on how the company could modularize their product family was created. In the example case the existing product structures were analyzed and the customer requirements, which cause the need for variation in the products, were studied. Good results were obtained in the example case, even though the scope of the case was focused on a limited number of crane models and structures. By applying of the process the part numbers could be reduced significantly. Also other benefits for the company could be obtained. During the example case some problems arose, which must be taken into account during a modularization project. The cooperation with the various experts in the company turned out to be very important. The process requires a great deal of information on products, product structures, design principles and customers. The com-pany’s marketing, sales and engineering teams have to participate in the process. It was also noticed, that by modularization alone, long-term benefits cannot be achieved. The company has to make sure, that the manufacturing of the products is made in a way that benefits from modularity. The sales persons have to be trained to sell modular products as well. In order to make sure, that the modular product structure is maintained in the future, the company has to have a certain person or group who owns the modules and interfaces. Their tasks include, for example, ensuring that changes in the products do not violate the modularity

GRINL1A Complex Transcription Unit Containing GCOM1, MYZAP, and POLR2M Genes Associates with Fully Penetrant Recessive Dilated Cardiomyopathy

Background: Familial dilated cardiomyopathy (DCM) is a monogenic disorder typically inherited in an autosomal dominant pattern. We have identified two Finnish families with familial cardiomyopathy that is not explained by a variant in any previously known cardiomyopathy gene. We describe the cardiac phenotype related to homozygous truncating GCOM1 variants.Methods and Results: This study included two probands and their relatives. All the participants are of Finnish ethnicity. Whole-exome sequencing was used to test the probands; bi-directional Sanger sequencing was used to identify the GCOM1 variants in probands' family members. Clinical evaluation was performed, medical records and death certificates were obtained. Immunohistochemical analysis of myocardial samples was conducted. A homozygous GCOM1 variant was identified altogether in six individuals, all considered to be affected. None of the nine heterozygous family members fulfilled any cardiomyopathy criteria. Heart failure was the leading clinical feature, and the patients may have had a tendency for atrial arrhythmias.Conclusions: This study demonstrates the significance of GCOM1 variants as a cause of human cardiomyopathy and highlights the importance of searching for new candidate genes when targeted gene panels do not yield a positive outcome.Peer reviewe

Prevalence of RPGR-Mediated Retinal Dystrophy in an Unselected Cohort of Over 5000 Patients

Purpose: Comprehensive genetic testing for inherited retinal dystrophy (IRD) is challenged by difficult-to-sequence genomic regions, which are often mutational hotspots, such as RPGR ORF15. The purpose of this study was to evaluate the diagnostic contribution of RPGR variants in an unselected IRD patient cohort referred for testing in a clinical diagnostic laboratory. Methods: A total of 5201 consecutive patients were analyzed with a clinically validated next-generation sequencing (NGS)-based assay, including the difficult-to-sequence RPGR ORF15 region. Copy number variant (CNV) detection from NGS data was included. Variant interpretation was performed per the American College of Medical Genetics and Genomics guidelines. Results: A confirmed molecular diagnosis in RPGR was found in 4.5% of patients, 24.0% of whom were females. Variants in ORF15 accounted for 74% of the diagnoses; 29% of the diagnostic variants were in the most difficult-to-sequence central region of ORF15 (c.2470-3230). Truncating variants made up the majority (91%) of the diagnostic variants. CNVs explained 2% of the diagnostic cases, of which 80% were one- or two-exon deletions outside of ORF15. Conclusions: Our findings indicate that high-throughput, clinically validated NGS-based testing covering the difficult-to-sequence region of ORF15, in combination with high-resolution CNV detection, can help to maximize the diagnostic yield for patients with IRD. Translational Relevance: These results demonstrate an accurate and scalable method for the detection of RPGR-related variants, including the difficult-to-sequence ORF15 hotspot, which is relevant given current and emerging therapeutic opportunities.Peer reviewe

Spatial patterns of microbial diversity and activity in an aged creosote-contaminated site

Restoration of polluted sites via in situ bioremediation relies heavily on the indigenous microbes and their activities. Spatial heterogeneity of microbial populations, contaminants and soil chemical parameters on such sites is a major hurdle in optimizing and implementing an appropriate bioremediation regime. We performed a grid-based sampling of an aged creosote-contaminated site followed by geostatistical modelling to illustrate the spatial patterns of microbial diversity and activity and to relate these patterns to the distribution of pollutants. Spatial distribution of bacterial groups unveiled patterns of niche differentiation regulated by patchy distribution of pollutants and an east-to-west pH gradient at the studied site. Proteobacteria clearly dominated in the hot spots of creosote pollution, whereas the abundance of Actinobacteria, TM7 and Planctomycetes was considerably reduced from the hot spots. The pH preferences of proteobacterial groups dominating in pollution could be recognized by examining the order and family-level responses. Acidobacterial classes came across as generalists in hydrocarbon pollution whose spatial distribution seemed to be regulated solely by the pH gradient. Although the community evenness decreased in the heavily polluted zones, basal respiration and fluorescein diacetate hydrolysis rates were higher, indicating the adaptation of specific indigenous microbial populations to hydrocarbon pollution. Combining the information from the kriged maps of microbial and soil chemistry data provided a comprehensive understanding of the long-term impacts of creosote pollution on the subsurface microbial communities. This study also highlighted the prospect of interpreting taxa-specific spatial patterns and applying them as indicators or proxies for monitoring polluted sites

Olemassa olevan tuoteperheen modularisointi

This Master of Science Thesis was made for Cargotec Oy. Variability of products and the different customer needs have increased the amount of part numbers that have to be maintained. This thesis seeks to find a solution for the problem. The aim of the thesis is to demonstrate how an existing product family can be modularized. Modularity has been studied a great deal in recent years and a number of different methods have been developed for modularizing product structures. This thesis introduc-es the Design Structure Matrix, Function Heuristics and Modular Function Deployment methods. The study of these methods, however, indicates that none of these are suitable as such for the modularization of an existing product family. The Brownfield Process is studied in more detail, because it is developed specifically for the modularization of existing product families. The thesis works as an instruction manual for the case company, in which modulariza-tion is explained and the different steps of the Brownfield Process are clarified in detail. The Brownfield Process was applied to the case company’s products and a proposal on how the company could modularize their product family was created. In the example case the existing product structures were analyzed and the customer requirements, which cause the need for variation in the products, were studied. Good results were obtained in the example case, even though the scope of the case was focused on a limited number of crane models and structures. By applying of the process the part numbers could be reduced significantly. Also other benefits for the company could be obtained. During the example case some problems arose, which must be taken into account during a modularization project. The cooperation with the various experts in the company turned out to be very important. The process requires a great deal of information on products, product structures, design principles and customers. The com-pany’s marketing, sales and engineering teams have to participate in the process. It was also noticed, that by modularization alone, long-term benefits cannot be achieved. The company has to make sure, that the manufacturing of the products is made in a way that benefits from modularity. The sales persons have to be trained to sell modular products as well. In order to make sure, that the modular product structure is maintained in the future, the company has to have a certain person or group who owns the modules and interfaces. Their tasks include, for example, ensuring that changes in the products do not violate the modularity

Spatial Patterns of Microbial Diversity and Activity in an Aged Creosote Contaminated Site

Restoration of polluted sites via in situ bioremediation relies heavily on the indigenous microbes and their activities. Spatial heterogeneity of microbial populations, contaminants and soil chemical parameters on such sites is a major hurdle in optimizing and implementing an appropriate bioremediation regime. We performed a grid-based sampling of an aged creosote-contaminated site followed by geostatistical modelling to illustrate the spatial patterns of microbial diversity and activity and to relate these patterns to the distribution of pollutants. Spatial distribution of bacterial groups unveiled patterns of niche differentiation regulated by patchy distribution of pollutants and an east-to-west pH gradient at the studied site. Proteobacteria clearly dominated in the hot spots of creosote pollution, whereas the abundance of Actinobacteria, TM7 and Planctomycetes was considerably reduced from the hot spots. The pH preferences of proteobacterial groups dominating in pollution could be recognized by examining the order and family-level responses. Acidobacterial classes came across as generalists in hydrocarbon pollution whose spatial distribution seemed to be regulated solely by the pH gradient. Although the community evenness decreased in the heavily polluted zones, basal respiration and fluorescein diacetate hydrolysis rates were higher, indicating the adaptation of specific indigenous microbial populations to hydrocarbon pollution. Combining the information from the kriged maps of microbial and soil chemistry data provided a comprehensive understanding of the long-term impacts of creosote pollution on the subsurface microbial communities. This study also highlighted the prospect of interpreting taxa-specific spatial patterns and applying them as indicators or proxies for monitoring polluted sites