Aβ1-42 monomers or oligomers have different effects on autophagy and apoptosis.

The role of autophagy and its relationship with apoptosis in Alzheimer disease (AD) pathogenesis is poorly understood. Disruption of autophagy leads to buildup of incompletely digested substrates, amyloid-β (Aβ) peptide accumulation in vacuoles and cell death. Aβ, in turn, has been found to affect autophagy. Thus, Aβ might be part of a loop in which it is both the substrate of altered autophagy and its cause. Given the relevance of different soluble forms of Aβ1-42 in AD, we have investigated whether monomers and oligomers of the peptide have a differential role in causing altered autophagy and cell death. Using differentiated SK-N-BE neuroblastoma cells, we found that monomers hamper the formation of the autophagic BCL2-BECN1/Beclin 1 complex and activate the MAPK8/JNK1-MAPK9/JNK2 pathway phosphorylating BCL2. Monomers also inhibit apoptosis and allow autophagy with intracellular accumulation of autophagosomes and elevation of levels of BECN1 and LC3-II, resulting in an inhibition of substrate degradation due to an inhibitory action on lysosomal activity. Oligomers, in turn, favor the formation of the BCL2-BECN1 complex favoring apoptosis. In addition, they cause a less profound increase in BECN1 and LC3-II levels than monomers without affecting the autophagic flux. Thus, data presented in this work show a link for autophagy and apoptosis with monomers and oligomers, respectively. These studies are likely to help the design of novel disease modifying therapies.

L’eficàcia de les suspensions judicials amb obligació de tractament de deshabituació. Factors que poden influir en la reducció o no de reincidència

Aquesta recerca està motivada per l’interès en les Mesures Penals Alternatives, concretament, en les suspensions judicials com a mesura més adient per a determinats subjectes amb perfils toxicològics i que requereixen d’una intervenció que es pot abordar en context comunitari. Per tal de valorar la seva eficàcia, l’equip d’investigadors s’ha centrat en els índexs de reincidència i aquells factors que poden influir a partir de l’anàlisi estadística d’una mostra de 237 subjectes sotmesos a l’obligació de tractament de deshabituació. Observant l’índex de reincidència, en funció de l’anàlisi de variables sociopersonals i judicials dels subjectes, es busquen aquells indicadors que poden ser eficaços per reduir la comissió de nous fets delictius. Del resultats obtinguts, es conclou que variables com una bona adherència familiar, una estabilitat laboral així com la finalització correcta d’un tractament de deshabituació aporten uns nivells de reincidència baixos. Igualment, es justifica l’atorgament de suspensions judicials com a eina punitiva més eficaç per a aquells subjectes amb característiques toxicològiques i necessitats rehabilitadores a causa de la seva addicció, atès que els nivells de reincidència obtinguts en aquesta recerca aporten uns índexs més baixos que els nivells actuals de reincidència penitenciària (cal tenir en compte, però, la diferència de perfils). Es conclou que aquestes mesures penals alternatives són una eina més integradora ja que es desenvolupen en l’entorn comunitari.

La eficacia de las suspensiones judiciales con obligación de tratamiento de deshabituación. Factores que pueden influir en la reducción o no de reincidencia

Esta investigación está motivada por el interés por las suspensiones judiciales como medida más adecuada para determinados sujetos con perfiles toxicológicos y que requieren una intervención que se puede abordar en un contexto comunitario. Con el fin de valorar su eficacia, el equipo de investigadores se ha centrado en los índices de reincidencia y aquellos factores que pueden influir a partir del análisis estadístico de una muestra de 237 sujetos sometidos a la obligación de tratamiento de deshabituación. Observando el índice de reincidencia, en función del análisis de variables sociopersonales y judiciales de los sujetos, se buscan aquellos indicadores que pueden ser eficaces para reducir la comisión de nuevos hechos delictivos. De los resultados obtenidos, se concluye que variables como una buena adherencia familiar, la estabilidad laboral o la finalización correcta de un tratamiento de deshabituación aportan unos niveles de reincidencia bajos Asimismo, se justifica el otorgamiento de suspensiones judiciales como herramienta punitiva más eficaz para aquellos sujetos con características toxicológicas y necesidades rehabilitadoras debido a su adicción, dado que los niveles de reincidencia obtenidos en esta investigación aportan unos índices más bajos que los niveles actuales de reincidencia penitenciaria (siempre teniendo en cuenta la diferencia de perfiles). Se concluye en este estudio que la aplicación de estas medidas penales alternativas son una herramienta más integradora debido a que se desarrolla dentro del entorno comunitario.

Long-term monitoring of post-stroke plasticity after transient cerebral ischemia in mice using in vivo and ex vivo diffusion tensor MRI.

WE USED A MURINE MODEL OF TRANSIENT FOCAL CEREBRAL ISCHEMIA TO STUDY: 1) in vivo DTI long-term temporal evolution of the apparent diffusion coefficient (ADC) and diffusion fractional anisotropy (FA) at days 4, 10, 15 and 21 after stroke 2) ex vivo distribution of a plasticity-related protein (GAP-43) and its relationship with the ex vivo DTI characteristics of the striato-thalamic pathway (21 days). All animals recovered motor function. In vivo ADC within the infarct was significantly increased after stroke. In the stroke group, GAP-43 expression and FA values were significantly higher in the ipsilateral (IL) striatum and contralateral (CL) hippocampus compared to the shams. DTI tractography showed fiber trajectories connecting the CL striatum to the stroke region, where increased GAP43 and FA were observed and fiber tracts from the CL striatum terminating in the IL hippocampus.Our data demonstrate that DTI changes parallel histological remodeling and recovery of function.

Disparities in work, risk and health between immigrants and native-born Spaniards

We analyse the impact of working and contractual conditions, particularly exposure to job risks, on the probability of acquiring a permanent disability, controlling for other personal and firm characteristics. We postulate a model in which this impact is mediated by the choice of occupation, with a level of risk associated with it. We assume this choice is endogenous, and that it depends on preferences and opportunities in the labour market, both of which may differ between immigrants and natives. To test this hypothesis we apply a bivariate probit model to data for 2006 from the Continuous Sample of Working Lives provided by the Spanish Social Security system, containing records for over a million workers. We find that risk exposure increases the probability of permanent disability arising from any cause - by almost 5%.

Prevalence of overweight in the Seychelles: 15 year trends and association with socio-economic status.

We assessed the 15-year trends in the distribution of body mass index (BMI) and the prevalence of overweight in the Seychelles (Indian Ocean, African Region) and the relationship with socio-economic status (SES). Three population-based examination surveys were conducted in 1989, 1994 and 2004. Occupation was categorized as 'labourer', 'intermediate' or 'professional'. Education was also assessed in 1994 and 2004. Between 1989 and 2004, mean BMI increased markedly in all sex and age categories (overall: 0.16 kg m(-2) per calendar year, which corresponds to 0.46 kg per calendar year). The prevalence of overweight (including obesity, BMI >or= 25 kg m(-2)) increased from 29% to 52% in men and from 50% to 67% in women. The prevalence of obesity (BMI >or= 30 kg m(-2)) increased from 4% to 15% in men and from 23% to 34% in women. Overweight was associated inversely with occupation in women and directly in men in all surveys. In multivariate analysis, overweight was associated similarly (direction and magnitude) to occupation and education. In conclusion, the increasing prevalence of overweight and obesity over time in all age, sex and SES categories suggests large-scale changes in societal obesogenic factors. The sex-specific association of SES with overweight suggests that prevention measures should be tailored accordingly.

Supply chain integration: studies on linking customer responsiveness and operational efficiency in logistics policy planning

Abstract The research problem in the thesis deals with improving the responsiveness and efficiency of logistics service processes between a supplier and its customers. The improvement can be sought by customizing the services and increasing the coordination of activities between the different parties in the supply chain. It is argued that to achieve coordination the parties have to have connections on several levels. In the framework employed in this research, three contexts are conceptualized at which the linkages can be planned: 1) the service policy context, 2) the process coordination context, and 3) the relationship management context. The service policy context consists of the planning methods by which a supplier analyzes its customers' logistics requirements and matches them with its own operational environment and efficiency requirements. The main conclusion related to the service policy context is that it is important to have a balanced selection of both customer-related and supplier-related factors in the analysis. This way, while the operational efficiency is planned a sufficient level of service for the most important customers is assured. This kind of policy planning involves taking multiple variables into the analysis, and there is a need to develop better tools for this purpose. Some new approaches to deal with this are presented in the thesis.The process coordination context and the relationship management context deal with the issues of how the implementation of the planned service policies can be facilitated in an inter-organizational environment. Process coordination includes typically such mechanisms as control rules, standard procedures and programs, but inhighly demanding circumstances more integrative coordination mechanisms may be necessary. In the thesis the coordination problems in third-party logistics relationship are used as an example of such an environment. Relationship management deals with issues of how separate companies organize their relationships to improve the coordination of their common processes. The main implication related to logistics planning is that by integrating further at the relationship level, companies can facilitate the use of the most efficient coordination mechanisms and thereby improve the implementation of the selected logistics service policies. In the thesis, a case of a logistics outsourcing relationship is used to demonstrate the need to address the relationship issues between the service provider andthe service buyer before the outsourcing can be done.The dissertation consists of eight research articles and a summarizing report. The principal emphasis in the articles is on the service policy planning context, which is the main theme of six articles. Coordination and relationship issues are specifically addressed in two of the papers.

Careers of Managers, Comparison between ICT and Paper Business Sectors

The purpose of this study is to increase understanding of how the managers build their early career in information and communication technology industry (ICT business sector) and pulp- and paper industry (paper business sector). The focus of the study is to explore the importance differing a business sectors have in influencing managerial careers. Business sectors can affect careers in several ways.Sectors have different history and traditions. Also the age structure of ICT personnel differs from the age structure of personnel in the paper industry. Managers in the ICT and paper sector are technically educated but in different disciplines. Differences exist also in ways of recruiting and developing commitment inpersonnel. The target group of this research, middle management engineering personnel, work in Finnish ICT and paper companies. Research data were gathered in April-December 2002 in South-Karelia by interviewing 30 managers and six directors working in three Finnish ICT companies and in three paper companies. The research issue is approached on two levels: the individual level and the organizational level. The managers related their career stories in focused interviews. Directors, representing the organizations, described the generalities of the business sector and gave background information on company policies, human relationshippractices, as well as career and human resource development. Results of the study contribute to research discussions of career, life-span reasoning, socialization and commitment. Career is conceived as a series of positions including everykind of hierarchical mobility and all kinds of positions in work. A manager's career develops in interaction with the organization and it can be seen as involving a socializing process in an organization as a consequence of experiences andchanges in positions. This research contributes to the understanding of the nature of career in the context of two business sectors. Universal career theories,for the most part, do not perceive the importance of business sector in determining career experience. This study concentrates on describing and understanding early careers in two different business areas, elements committing managers to particular business sectors and the actions of companies in that particular sector. While career research began in the middle of 1950s, the theoretical basis of career research seems to be quite fragmented still. However, a dichotomy is consistently presented between traditional, hierarchical career research and boundaryless career thinking. In this research we examine how these old and new career concepts are evidence in the ICT and paper sectors. Careers are changing from formal, hierarchy-based structures to more fluid arrangements. The new boundaryless career concept captures territory from old career thinking. Mobility between employers, networks, and changing hierarchical structures in organizations, as well as personal and family reasons are theorized to bring changes to careers patterns in the future. However, the pace of this change in careers will vary between the ICT and paper business sectors. Findings of this research indicate that business sector has an effect on how managerial careers develop. The environment where career is developed differs between ICT and paper sectors. Careers begin differently in the two environments and the speed of career progression is distinct. ICT careers are built within the business sector whereas paper careers are made inside one company. Also recruiting and socialization practices differ from one sector to the other.

Establishing intercompany relationships: Motives and methods for successful collaborative engagement

This study explores the early phases of intercompany relationship building, which is a very important topic for purchasing and business development practitioners as well as for companies' upper management. There is a lot ofevidence that a proper engagement with markets increases a company's potential for achieving business success. Taking full advantage of the market possibilities requires, however, a holistic view of managing related decision-making chain. Most literature as well as the business processes of companies are lacking this holism. Typically they observe the process from the perspective of individual stages and thus lead to discontinuity and sub-optimization. This study contains a comprehensive introduction to and evaluation of literature related to various steps of the decision-making process. It is studied from a holistic perspective ofdetermining a company's vertical integration position within its demand/ supplynetwork context; translating the vertical integration objectives to feasible strategies and objectives; and operationalizing the decisions made through engagement with collaborative intercompany relationships. The empirical part of the research has been conducted in two sections. First the phenomenon of intercompany engagement is studied using two complementary case studies. Secondly a survey hasbeen conducted among the purchasing and business development managers of several electronics manufacturing companies, to analyze the processes, decision-makingcriteria and success factors of engagement for collaboration. The aim has been to identify the reasons why companies and their management act the way they do. As a combination of theoretical and empirical research an analysis has been produced of what would be an ideal way of engaging with markets. Based on the respective findings the study concludes by proposing a holistic framework for successful engagement. The evidence presented throughout the study demonstrates clear gaps, discontinuities and limitations in both current research and in practical purchasing decision-making chains. The most significant discontinuity is the identified disconnection between the supplier selection process and related criteria and the relationship success factors.

Time patterns and perceptions of online learning success factors

Online learning provides the opportunity to work on academic tasks at any time at the same time as doing other activities, such as using in web 2.0 tools. This study identifies factors that contribute to success in online learning from the students¿ perspective and their relationship with time patterns. A survey of learning outputs was used to find relationships between students¿ satisfaction, knowledge acquisition and knowledge transfer with time for working on academic tasks. In this study, 199 students from a university in Mexico completed the survey. Findings suggest that knowledge transfer has a significant association with the number of hours online per day, hours spent on social networks and the use made of e-learning during working hours. Learner satisfaction has a strong relationship with the time in years a learner has been using the Internet and the number of hours devoted to the course per week. The findings of this research will be helpful for faculty and instructional designers for implementing learning strategies.

Worldwide Population Structure, Long-Term Demography, and Local Adaptation of Helicobacter pylori.

Helicobacter pylori is an important human pathogen associated with serious gastric diseases. Owing to its medical importance and close relationship with its human host, understanding genomic patterns of global and local adaptation in H. pylori may be of particular significance for both clinical and evolutionary studies. Here we present the first such whole genome analysis of 60 globally distributed strains, from which we inferred worldwide population structure and demographic history and shed light on interesting global and local events of positive selection, with particular emphasis on the evolution of San-associated lineages. Our results indicate a more ancient origin for the association of humans and H. pylori than previously thought. We identify several important perspectives for future clinical research on candidate selected regions that include both previously characterized genes (e.g., transcription elongation factor NusA and tumor necrosis factor alpha-inducing protein Tipα) and hitherto unknown functional genes.

The Dynamic Customer Portfolio Method in Customer Relationship Management

Tutkielman tavoitteena on määritellä keskeiset ja sopivat asiakasportfoliomallit ja asiakasmatriisit asiakassuhteen määrittämiseen. Tutkimus keskittyy asiakassuhteen arvottamiseen ja avainasiakkaiden määrittämiseen kohdeyrityksessä. Keskeisimmät ja sopivimmat asiakasportfliomallit huomioidaan asiakkaiden arvioinnissa. Tutkielman teoriaosassa esitellään tunnetuimmat ja käytetyimmät asiakasportfoliomallit ja matriisit alan kirjallisuuden perusteella. Tämän lisäksi asiakasportfoliomalleihin yhdistetään näkökulmia suhdemarkkinoinnin, asiakkuuksien johtamisen ja tuoteportfolioiden teorioista. Keskeisimmät kirjallisuuden lähteet ovat johtamisen ja markkinoinnin alalta. Tutkielman empiriaosassa esitellään kohdeyritys ja sen tämän hetkinen asiakassuhteiden johtamiskäytäntö. Lisäksi tehdään parannusehdotuksia kohdeyrityksen nykyiseen asiakassuhteiden arvottamismenetelmään jotta asiakassuhteiden arvon laskeminen vastaisi mahdollisimman hyvin kohdeyrityksen nykyisiä tarpeita. Asiakassuhteen arvon määrittämiseksi käytetään myös fokusryhmähaastattelua. Avainasiakkaat määritellään ja tilannetta havainnollistetaan sijoittamalla avainasiakkaat asiakasportfolioon.

Obese, smoker, and obese smoker : is there a general lifestyle gradient?

Aim: Obesity and smoking are major CVD risk factors and may be associated with other unfavourable lifestyle behaviours. Our aim was to investigate the significance of obesity, heavy smoking, and both combined in terms of prevalence trends and their relationship with other lifestyle factors. Methods: We used data from the population-based cross-sectional Swiss Health Survey (5 waves, 1992-2012) comprising 85,575 individuals aged 18 years. Height, weight, and smoking status were self-reported. We used multinomial logistic regression to analyse differences in lifestyle for the combinations of BMI category and smoking status, focusing on obese and heavy smokers. We defined normal-weight never smokers as reference.

Plasma cell and terminal B-cell differentiation in mantle cell lymphoma mainly occur in the SOX11-negative subtype.

Mantle cell lymphoma is a mature lymphoid neoplasm characterized by the t(11;14)(q13;q32) and cyclin D1 overexpression. SOX11 is a transcription factor commonly overexpressed in these tumors but absent in most other mature B-cell lymphomas whose function is not well understood. Experimental studies have shown that silencing of SOX11 in mantle cell lymphoma cells promotes the shift from a mature B cell into an early plasmacytic differentiation phenotype, suggesting that SOX11 may contribute to tumor development by blocking the B-cell differentiation program. The relationship between SOX11 expression and terminal B-cell differentiation in primary mantle cell lymphoma and its relationship to the plasmacytic differentiation observed in occasional cases is not known. In this study we have investigated the terminal B-cell differentiation phenotype in 60 mantle cell lymphomas, 41 SOX11-positive and 19 SOX11-negative. Monotypic plasma cells and lymphoid cells with plasmacytic differentiation expressing cyclin D1 were observed in 7 (37%) SOX11-negative but in none of 41 SOX11-positive mantle cell lymphomas (P<0.001). Intense cytoplasmic expression of a restricted immunoglobulin light chain was significantly more frequent in SOX11-negative than -positive tumors (58 vs 13%) (P=0.001). Similarly, BLIMP1 and XBP1 expression was also significantly more frequent in SOX11-negative than in -positive cases (83 vs 34% and 75 vs 11%, respectively) (P=0.001). However, no differences in the expression of IRF4/MUM1 were observed among these subtypes of mantle cell lymphoma. In conclusion, these results indicate that SOX11-negative mantle cell lymphoma may be a particular subtype of this tumor characterized by more frequent morphological and immunophenotypic terminal B-cell differentiation features that may be facilitated by the absence of SOX11 transcription factor.

Maintenance and development of supplier relationships in an environment of irregular demand

The main target of the study was to find ideas for maintenance and development of supplier relations in irregular business environment. The other aim was to find out the suppliers’ opinions concerning the case company and the relationship between the companies. The study was conducted by using both qualitative and quantitative research methods. A mail survey was used to find out supplier opinions and an interview to find out suppliers’ ideas for relationship maintenance and development. It was found out that the use of relational elements is essential in the relationship maintenance in an irregular environment. In development of supplier relations the company should make better use of its suppliers’ potential, assure better flow of information and utilize the possibilities of Supplier Relationship Management.