IMP2 provides an alternative to LIN28B for LET-7 target gene protection and glioma stem cell maintenance

Glioblastoma multiforme (GBM) is the most frequent and lethal primary brain tumor in adults. Accumulating evidence suggests that tumors comprise a hierarchical organization that is, at least partially, not genetically driven. Cells that reside at the apex of this hierarchy are commonly referred to as cancer stem cells (CSCs) and are believed to largely contribute to recurrence and therapeutic failure. Although the complexity of epigenetic regulation of the genome precludes prediction as to which epigenetic changes dominate CSC specification in different cancer types, the ability of microRNAs (miRNAs) to fine-tune expression of entire gene networks places them among prime candidates for establishing CSC properties. In this study we characterized the miRNA expression profile of primary GBM grown either under conditions that enrich for GSCs or their differentiated non-tumorigenic progeny (DGCs). Although, we identified a subset of miRNAs that was strongly differentially expressed between GSCs and DGCs, we observed that in GSCs both let-7 and, paradoxically, their target genes are highly expressed, suggesting protection against let-7 action. Using PAR-CLIP we show that insulin-like growth factor-2 mRNA-binding protein 2 (IMP2) provides a mechanism for let-7 target gene protection that represents an alternative to LIN28A/B, which abrogates let-7 biogenesis in normal embryonic and certain malignant stem cells. By direct binding to miRNA recognition elements, IMP2 protects its targets from let-7 mediated decay. Importantly, depletion of IMP2 in GSCs strongly impairs their self- renewal properties and tumorigenicity in vivo, a phenotype that can be rescued by expression of LIN28B, suggesting that IMP2 mainly contributes to GSC maintenance by protecting let-7 target genes from silencing. Using mouse models, we show that depletion of IMP2 in neural stem cells (NSCs) induces let-7 target gene down-regulation, impairs their clonogenic capacity, and affects differentiation. Taken together, our observations describe a novel regulatory function of IMP2 in the let-7 axis whereby it supports GSC and NSC specification. Résumé (Français) Le glioblastome (GBM) est la tumeur primaire maligne du cerveau la plus fréquente. De nombreuses études ont démontré l'existence d'une organisation hiérarchique des cellules cancéreuses liée à des mécanismes épigénétiques. Les cellules qui se trouvent au sommet de cette hiérarchie sont appelées cellules souches cancéreuses (CSC), et contribuent à l'échec thérapeutique. Bien que la complexité des régulateurs épigénétiques permette difficilement de prédire quel mécanisme contribue le plus aux propriétés des CSC, la capacité des microRNAs (miRNAs) de réguler des réseaux entiers de gènes, les placent comme des candidats de premiers choix. Ici, nous avons caractérisé le profil d'expression des miRNAs dans des tumeurs primaires de GBM cultivées dans des conditions qui enrichissent soit pour les CSC, soit pour leur contrepartie de cellules cancéreuses différences (CCD). De manière surprenante et paradoxale la famille de miRNA let-7 et leurs gènes cibles étaient hautement exprimés dans les CSC, suggérant un mécanisme de protection contre l'action des let-7. Avec l'aide de la technologie PAR-CLIP, nous démontrons que la protéine IMP2, protège les mRNAs de l'action des let-7 et représente une alternative à Lin28A/B, qui d'ordinaire réprime fortement la maturation des let-7 dans les cellules souches embryonnaires et divers cancers. En se liant à la région ciblée par les let-7, IMP2 protège ses transcrits de l'action de cette classe de microRNA qui est tumoro-supressive. La déplétion d'IMP2 dans des CSC de GBM réduit fortement leur clonogénicité in vitro et leur tumorigénicité in vivo. Ceci peut être reversé en introduisant Lin28B dans des CSC de GBM, suggérant qu'IMP2 exerce ses fonctions pro-tumorigéniques en modulant l'axe let-7. Avec l'aide de modèles murins, nous observons que la déplétion de IMP2 dans les cellules souches neurales (CSN) induit une baisse de leur clonogénicité et des cibles des miRNAs let-7, suggérant une conservation de ce mécanisme entre les CSC de GBM et les CSN. En résumé, nos observations définissent une nouvelle fonction de IMP2 dans l'axe let-7 par lequel il contribue au maintien des propriétés des CSC et des CSN.

Konekohtaiset kunnossapidon kustannukset ohutlevy-yrityksessä

Diplomityön tavoitteena on laskea kohdeyrityksen tehtaan koneiden kunnossapidosta aiheutuvat kustannukset. Koneiden kunnossapidon kustannusten laskemisen lisäksi työn aikana laaditaan kunnossapidon kustannusten kuukausittainen raportti sekä tehdään kunnossapitoa helpottava ohjelma. Kunnossapidon kustannukset jaotellaan kahteen osaan, jotka ovat välittömät ja välilliset kustannukset. Työn teoriaosassa käydään läpi kustannuslaskentaa, kunnossapidon teoriaa sekä kapasiteetin riittävyyttä. Empiriaosassa esitellään kohdeyritys ja kunnossapidon nykytila. Tämän jälkeen käydään läpi koneiden kunnossapidon kustannusten laskentamalli ja kunnossapitojärjestelmä. Esittelyjen jälkeen analysoidaan työn tuloksia ja ehdotetaan muutamia kehitysvaihtoehtoja. Diplomityön tuloksista on huomattavissa, että kohdeyrityksen tehtaan koneiden kunnossapidon kustannukset ovat pääasiassa välittömiä kustannuksia. Koneiden kunnossapidon kustannusten selvittäminen toi esille kustannusten vaikutuksen eri tuotteisiin, niiden omakustannusarvoihin ja katteisiin. Joidenkin tuotteiden katteet muuttuivat jopa negatiivisiksi. Vaikka kunnossapidon konekohtaiset kustannukset saadaan pysymään samana, kehittämällä tuotantoa voidaan vähentää merkittävästi tuotekohtaisia kunnossapidon kustannuksia.

Organizing automation maintenance business in Russia

The target of this thesis is to find out potential of automation maintenance services in Russian industry, especially in the region of St. Petersburg. At the beginning of this study the industrial maintainability and process efficiency are discussed from the point of view of process automation. A survey of the present technology and maintenance methods has been made during five visits to local plants. The results of the interviews are analyzed numerically to clarify the common needs and the potential of automation maintenance services. The most interesting services are evaluated by their required resources to find economically justified solutions for the needs of the industry. As results of this study, some service products that would interest interviewed companies have been introduced. These could be offered to the industry to enhance cost-efficiency and productivity of processes.

Materiaalin varaus globaalissa paperiteollisuuden järjestelmässä

Tärkeä osa paperiteollisuuden myyntitapahtumaa on tarkistaa tilatun tuotteen saatavuus ja toimittamisen aikataulu. Käytännössä tämä tarkoittaa kuljetusten, tuotannon ja valmistetun materiaalin tarkistamista. Tässä työssä on tehty olemassa olevan vapaan materiaalin tarkistaminen. Materiaalin tarkastus ei ole uusi idea, mutta kapasiteettivarauksen uudelleen toteutus on tehty tulevan ylläpitotyön helpottamiseksi ja järjestelmän suorituskyvyn parantamiseksi. Lisäksi uutta varauslogiikkaa pystytään käyttämään muissakin tuotannonohjausjärjestelmän ohjelmistoissa. Kapasiteettivaraukseen on myös rakennettu uusi kustannuspohjainen priorisointijärjestelmä, ja mietitty kuinka tätä olisi tulevaisuudessa helppo jalostaa. Erityishuomiota on kiinnitetty toiminnan läpinäkyvyyteen eli siihen, että tarkistuslogiikka kertoo syyt eri materiaalin hylkäämiseen. Työn yhteydessä on analysoitu materiaalivarauksen aiheuttamaa kuormaa järjestelmässä ja mietitty eri tekniikoita suorituskyvyn parantamiseksi.

Tuotetiedon soveltaminen varastotiedon hallinnan parantamisessa

Inventory data management is defined as an accurate creation and maintenance of item master data, inventory location data and inventory balances per an inventory location. The accuracy of inventory data is dependent of many elements of the product data management like the management of changes during a component’s life-cycle and the accuracy of product configuration in enterprise resource planning systems. Cycle-counting is counting of inventory balances per an inventory location and comparing them to the system data on a daily basis. The Cycle-counting process is a way to measure the accuracy of the inventory data in a company. Through well managed cycle-counting process a company gets a lot of information of their inventory data accuracy. General inaccuracy of the inventory data can’t be fixed through only assigning resources to the cycle-counting but the change requires disciplined following of the defined processes from all parties involved in updating inventory data through a component’s life-cycle. The Processes affecting inventory data are mapped and the appropriate metrics are defined in order to achieve better manageability of the inventory data. The Life-cycles of a single component and of a product are used in evaluation of the processes.

Offering planning process development: Bridging the Offering Gaps and Consolidating Top Priority Needs in Product Offering

The aim of this Thesis is to study how to manage the front-end of the offering planning process. This includes actual process development and methods to gather and analyze information to achieve the best outcome in customer oriented product offering. Study is carried out in two parts: theoretical part and company related part. Theoretical framework is created introducing different types of approaches to manage product planning processes. Products are seen as platforms and they are broken down to subsystems to show different parts of the development. With the help of the matrix-based approaches product platform related information is gathered and analyzed. In this kind of analysis business/market drivers and cus-tomer/competitor information are connected with product subsystems. This gives possibilities to study product gaps/needs and possible future ideas/scenarios in different customer segments. Company related part consists of offering planning process development in real company environment. Process formation includes documents and tools that guide planning from the information gathering to the prioritization and decision making.

Assessment of an information product project success: case business blueprint

The objective of this study was to find out how project success can be measured in a case where the output of a project is an intangible information product, what kind of framework can be used to evaluate the project success, and how the project assessment can be done in practice. As a case example, the success of a business blueprint project was assessed from the product point of view. A framework for assessing business blueprint project success was made based on a literature review. Furthermore, separate frameworks for measuring information product quality and project costs were developed. The theory of business blueprinting was discovered not to be firmly institutionalized and it is briefly covered in the thesis. The possible net benefits from the strategic business process harmonization were noted to be much more significant than the costs of the business blueprint project. The project was seen as a sufficient success from the viewpoint of the created output.

Creating Global Competitive Advantage by Global Product Technology Transfers

Globalization is the trend which is realized in all areas in today’s business world. Pressure for cost reduction, changes in market situation and available scale economies have changed business environment more global than ever. To respond to new situation, companies are establishing global strategies. In this thesis, available global competitive advantages in electrical machine industry are studied in context of gaining them by global technology transfers. In theory part, establishing global strategy and competitive advantage is considered with connection to global sourcing and supply chain management. Additionally, market development in 21st century and its impact on global strategies is studied. In practice, global manufacturing is enabled by technology transfer projects. Smooth and fast project implementation enables faster and more flexible production ramp up. By starting the production available competitive advantages can be realized. In this thesis the present situation of technology transfer projects and the risks and advantages related to global manufacturing are analyzed. The analysis of implemented technology transfer projects indicates that project implementation is in good level. For further development of project execution 10 minor suggestions could be presented with two major ones: higher level standardization and development of product information model to support better global manufacturing.

Structuration and branding of a religious tourism product: Catalonia sacra

This article aims to provide an overview of the products Catalonia has to offer in terms of religious tourism. The growing interest in this kind of tourism worldwide, and in Catalonia itself, along with the region's wealth of religious heritage (particularly connected to the Christian Church) contrast with the lack of religion-based tourism products available, which results in its absence from the region's image as a tourism destination. In view of this, the Faculty of Tourism (University of Girona), the Vic Bishopric's Albergueria-Centre for Cultural Dissemination and the Tarraconense Episcopal Conference's Interdiocese Secretariat for the Custody and Promotion of Holy Art (SICPAS) decided to address the situation with the help of funding from the Autonomous Government of Catalonia. In order to re-position Christian religious heritage in the image of Catalonia as a tourist destination, the aforementioned parties embarked upon a project to set up a series of routes throughout the region, branded under the name Catalonia Sacra

Product Data Managemet as a Key Success Factor in After Sales Business

The objective of this master’s thesis is to define Larox´s Product Data present state and future development needs from after sales point of view. In particular the object was to investigate after sales needs, which data related to products need to be managed by using Product Data Management. Empirical material of thesis was collected mainly through interviews, benchmark visits, and personal experience. Among the interviewees were internal stakeholders who are closely related to the product process, as well as external stakeholders. Interviews revealed that each stakeholder group has deviating needs for product data management and that at present all the needs are not met to take the best possible way. The main requirement was availability of up-to-date information, which plays a key role in after sales business. At the end of study is concentrated to find development targets at Larox, especially from after sales point of view. In addition, consideration of how the product data management advantages can utilized in making internal processes more efficient. Development needs are collected together as project descriptions, whose headings are shown at the end of the study.

Organic chicken product authentication: state-of-the-art and future perspectives

Organic food products are highly susceptible to fraud. Currently, administrative controls are conducted to detect fraud, but having an analytical tool able to verify the organic identity of food would be very supportive. The state-of-the-art in food authentication relies on fingerprinting approaches that find characteristic analytical patterns to unequivocally identify authentic products. While wide research on authentication has been conducted for other commodities, the authentication of organic chicken products is still in its infancy. Challenges include finding fingerprints to discriminate organic from conventional products, and recruiting sample sets that cover natural variability. Future research might be oriented towards developing new authentication models for organic feed, eggs and chicken meat, keeping models updated and implementing them into regulations. Meanwhile, these models might be very supportive to the administrative controls directing inspections towards suspicious fraudulent samples.

Predictors of psychiatric hospitalization during 6 months of maintenance treatment with olanzapine long-acting injection: post hoc analysis of a randomized, double-blind study.

BACKGROUND: Hospitalization is a costly and distressing event associated with relapse during schizophrenia treatment. No information is available on the predictors of psychiatric hospitalization during maintenance treatment with olanzapine long-acting injection (olanzapine-LAI) or how the risk of hospitalization differs between olanzapine-LAI and oral olanzapine. This study aimed to identify the predictors of psychiatric hospitalization during maintenance treatment with olanzapine-LAI and assessed four parameters: hospitalization prevalence, incidence rate, duration, and the time to first hospitalization. Olanzapine-LAI was also compared with a sub-therapeutic dose of olanzapine-LAI and with oral olanzapine. METHODS: This was a post hoc exploratory analysis of data from a randomized, double-blind study comparing the safety and efficacy of olanzapine-LAI (pooled active depot groups: 405 mg/4 weeks, 300 mg/2 weeks, and 150 mg/2 weeks) with oral olanzapine and sub-therapeutic olanzapine-LAI (45 mg/4 weeks) during 6 months' maintenance treatment of clinically stable schizophrenia outpatients (n=1064). The four psychiatric hospitalization parameters were analyzed for each treatment group. Within the olanzapine-LAI group, patients with and without hospitalization were compared on baseline characteristics. Logistic regression and Cox's proportional hazards models were used to identify the best predictors of hospitalization. Comparisons between the treatment groups employed descriptive statistics, the Kaplan-Meier estimator and Cox's proportional hazards models. RESULTS: Psychiatric hospitalization was best predicted by suicide threats in the 12 months before baseline and by prior hospitalization. Compared with sub-therapeutic olanzapine-LAI, olanzapine-LAI was associated with a significantly lower hospitalization rate (5.2% versus 11.1%, p < 0.01), a lower mean number of hospitalizations (0.1 versus 0.2, p = 0.01), a shorter mean duration of hospitalization (1.5 days versus 2.9 days, p < 0.01), and a similar median time to first hospitalization (35 versus 60 days, p = 0.48). Olanzapine-LAI did not differ significantly from oral olanzapine on the studied hospitalization parameters. CONCLUSIONS: In clinically stable schizophrenia outpatients receiving olanzapine-LAI maintenance treatment, psychiatric hospitalization was best predicted by a history of suicide threats and prior psychiatric hospitalization. Olanzapine-LAI was associated with a significantly lower incidence of psychiatric hospitalization and shorter duration of hospitalization compared with sub-therapeutic olanzapine-LAI. Olanzapine-LAI did not differ significantly from oral olanzapine on hospitalization parameters.

Informed recommender: basing recommendations on consumer product reviews

Recommender systems attempt to predict items in which a user might be interested, given some information about the user's and items' profiles. Most existing recommender systems use content-based or collaborative filtering methods or hybrid methods that combine both techniques (see the sidebar for more details). We created Informed Recommender to address the problem of using consumer opinion about products, expressed online in free-form text, to generate product recommendations. Informed recommender uses prioritized consumer product reviews to make recommendations. Using text-mining techniques, it maps each piece of each review comment automatically into an ontology

Bio-based composites from stone groundwood applied to new product development

This paper deals with the product design, engineering, and material selection intended for the manufacturing of an eco-friendly chair. The final product is expected to combine design attributes with technical and legal feasibility with the implementation of new bio-based materials. Considering the industrial design, a range of objectives and trends were determined after setting the market requirements, and the final concept was proposed and modeled. The product geometry, production technology, and legal specifications were the input data for product engineering. The material selection was based on the technical requirements. Polypropylene (PP) composite materials based on coupled-fiberglass, sized-fiberglass, and coupled-stone ground wood reinforcements were prepared and characterized. Final formulations based on these PP composites are proposed and justified