HGF inhibits BMP-induced osteoblastogenesis: Possible implications for the bone disease of multiple myeloma.

Udgivelsesdato: 2007-Apr-

Municipal activation policy: A case study of the practical work with unemployed social assistance recipients

In the 1990s, many municipalities developed local activation programs for social assistance recipients as a response to increasing social assistance expenditures. This study investigates the practical implementation of municipal activation policies in two different activation programs, Jobbcentrum in Skärholmen and Källan in Osby. The purpose with the study is to highlight how the front-line workers systematically translate activation policy into practice in their interactions with the clients. The study utilizes a street-level bureaucracy perspective, which illuminates the role of bureaucratic and professional discretion and how institutional factors shape the practical responses of front-line staff. Coping behaviors at the ground influences the practical work with activation requirements. The staff develop such coping strategies to manage working conditions marked by ambiguous legislation, organizational pressures, limited resources, and little responsibility for program accountability. Findings from this study suggest that the implementation practices in Skärholmen and Osby frequently diverge from formal intentions of activation policy and the programs’ own goals and descriptions of their work.Municipal activation policy; social assistance; street-level bureaucracy theory; front-line workers; implementation; Jobbcentrum; Källan

Analysis of the Norwegian power market with prediction of day-ahead spot prices by means of Linear Regression and Machine Learning.

Elektrisk strøm skiller seg fra de fleste andre omsettelige råvarer ved at den egner seg dårlig til lagring. Ved å kombinere økonometri og maskinlæringsmetoder i kraftmarkedet kan man forsøke å predikere hvor det er balanse mellom produksjon og forbruk, samt forsøke å predikere prisen. De dominerende metodene som brukes for å gi prognoser er svært avanserte maskinlæringsmodeller. Ettersom de ulike metodene er bygget på ulike forutsetninger, må man kunne navigere og tilpasse seg typen data som er tilgjengelig. Vi har brukt data fra ulike åpne og private kilder for å benytte både statistiske og maskinlæringstilnærminger for å a) analysere og b) predikere kraftmarkedet. Resultatet av oppgaven er en noe presis maskinlæringsmodell, som til en viss grad er i stand til å forutsi strømprisen. Funnene våre har resultert i en dypere forståelse av hva som driver strømprisen, noe vi finner avgjørende for å lage prognoser. Variablene som blir benyttet ble valgt manuelt, noe som sett i ettertid kan ha ført til reliabilitetsproblemer på grunn av utvalgsskjevhet.Electricity differs from most other tradeable commodities in that it cannot easily be stored. Combining econometric and machine learning methods in the electricity market can help predict where there is a balance between generation and consumption, as well as what the price will be. The dominant methods used to provide forecasts are severely advanced machine learning models. As different methods are built on different assumptions, one must be able to navigate and adapt to the type of data available. We have used data from various open- and private sources to utilize both statistical and machine learning approaches to a) analyze and b) forecast the electricity market. The result of our study yields a some-what precise machine learning model, that to some degree can forecast the electricity price. Our findings have resulted in a deeper understanding of what drives the electricity price, which we find essential to make forecasts. The variables are chosen manually, and looking backwards, might have led to some reliability issues as it may have introduced selection bias to the dataset

Equine enteroid-derived monolayers recapitulate key features of parasitic intestinal nematode infection

Stem cell-derived organoid cultures have emerged as attractive experimental models for infection biology research regarding various types of gastro-intestinal pathogens and host species. However, the large size of infectious nematode larvae and the closed structure of 3-dimensional organoids often hinder studies of the natural route of infection. To enable easy administration to the apical surface of the epithelium, organoids from the equine small intestine, i.e. enteroids, were used in the present study to establish epithelial monolayer cultures. These monolayers were functionally tested by stimulation with IL-4 and IL-13, and/or exposure to infectious stage larvae of the equine nematodes Parascaris univalens, cyathostominae and/or Strongylus vulgaris. Effects were recorded using transcriptional analysis combined with histochemistry, immunofluorescence-, live-cell- and scanning electron microscopy. These analyses revealed heterogeneous monolayers containing both immature and differentiated cells including tuft cells and mucus-producing goblet cells. Stimulation with IL-4/IL-13 increased tuft- and goblet cell differentiation as demonstrated by the expression of DCLK1 and MUC2. In these cytokine-primed monolayers, the expression of MUC2 was further promoted by co-culture with P. univalens. Moreover, live-cell imaging revealed morphological alterations of the epithelial cells following exposure to larvae even in the absence of cytokine stimulation. Thus, the present work describes the design, characterization and usability of an experimental model representing the equine nematode-infected small intestinal epithelium. The presence of tuft cells and goblet cells whose mucus production is affected by Th2 cytokines and/or the presence of larvae opens up for mechanistic studies of the physical interactions between nematodes and the equine intestinal mucosa

Municipal activation policy: A case study of the practical work with unemployed social assistance recipients

In the 1990s, many municipalities developed local activation programs for social assistance recipients as a response to increasing social assistance expenditures. This study investigates the practical implementation of municipal activation policies in two different activation programs, Jobbcentrum in Skärholmen and Källan in Osby. The purpose with the study is to highlight how the front-line workers systematically translate activation policy into practice in their interactions with the clients. The study utilizes a street-level bureaucracy perspective, which illuminates the role of bureaucratic and professional discretion and how institutional factors shape the practical responses of front-line staff. Coping behaviors at the ground influences the practical work with activation requirements. The staff develop such coping strategies to manage working conditions marked by ambiguous legislation, organizational pressures, limited resources, and little responsibility for program accountability. Findings from this study suggest that the implementation practices in Skärholmen and Osby frequently diverge from formal intentions of activation policy and the programs’ own goals and descriptions of their work

Bone morphogenetic protein-2/4 and bone morphogenetic protein receptor type IA expression in metastatic and nonmetastatic oral squamous cell carcinoma

Purpose The study aimed to analyze the expression of bone morphogenetic protein-2/4 (BMP-2/4) and its receptor BMPR-IA (BMP receptor type IA) in metastatic and nonmetastatic oral squamous cell carcinoma (OSCC) and its implications for disease prognosis. Materials and methods The experimental group included 16 cases of OSCC without metastasis and 7 cases of OSCC with metastasis. The presence or absence of nodal metastasis was used as a parameter for the evaluation of disease prognosis. Ten cases of oral fibroepithelial hyperplasia were selected as the control group. The expression of BMP-2/4 and BMPR-IA was analyzed by immunohistochemistry. Results In the experimental group with metastasis, strong expression of BMP-2/4 was observed in most cases (71.4%), whereas BMPR-IA exhibited weak expression (85.7%). In the experimental group without metastasis, there was strong expression of BMP-2/4 (62.5%) and BMPR-IA (100%). A significant association was observed between the prognosis of OSCC and the intensity of BMP-2/4 staining (P = .002). Weak immunoreactivity to BMP-2/4 and BMPR-IA was observed in all control specimens. Conclusions The results suggest that strong expression of BMP-2/4, associated with low expression of BMPR-IA, observed in metastatic OSCC has a prognostic value, with the loss of responsiveness to BMPs through the loss of expression of their receptors being indicative of the development of metastasis

Osteoprotegerin is bound, internalized, and degraded by multiple myeloma cells

Multiple myeloma (MM) is a hematologic malignancy characterized by accumulation of plasma cells in the bone marrow (BM). Bone destruction is a complication of the disease and is usually associated with severe morbidity. The balance between receptor activator of nuclear factor-kappaB (NF-kappaB) ligand and osteoprotegerin (OPG) is of major importance in bone homeostasis. We have recently shown that serum OPG levels are lower in patients with myeloma than in healthy individuals. Here we show that myeloma cells can bind, internalize, and degrade OPG, thereby providing a possible explanation for the lower levels of OPG in the BM of patients with MM. This process is dependent on interaction of OPG with heparan sulfates on the myeloma cells. The results suggest a novel biologic mechanism for the bone disease associated with MM and that treatment of the bone disease with OPG lacking the heparin-binding domain should be considered.</p

Interaction of classical swine fever virus with dendritic cells

Functional disruption of dendritic cells (DCs) is an important strategy for viral pathogens to evade host defences. Monocytotropic viruses such as classical swine fever virus (CSFV) could employ such a mechanism, since the virus can suppress immune responses and induce apoptosis without infecting lymphocytes. Here, CSFV was shown to infect and efficiently replicate in monocyte- and in bone marrow-derived DCs. Interestingly, the infected DCs displayed neither modulated MHC nor CD80/86 expression. Stimulation of DCs with IFN-/TNF- or polyinosinic¿polycytidylic acid (pIC) induced phenotypic maturation with increased MHC and CD80/86 expression, both with mock-treated and infected DCs. In addition, the T cell stimulatory capacity of CSFV-infected DCs was maintained both in a polyclonal T cell stimulation and in specific antigen-presentation assays, requiring antigen uptake and processing. Interestingly, similar to macrophages, CSFV did not induce IFN- responses in these DCs and even suppressed pIC-induced IFN- induction. Other cytokines including interleukin (IL)-6, IL-10, IL-12 and TNF- were not modulated. Taken together, these results demonstrated that CSFV can replicate in DCs and control IFN type I responses, without interfering with the immune reactivity. These results are interesting considering that DC infection with RNA viruses usually results in DC activation

Murine 5T multiple myeloma cells induce angiogenesis in vitro and in vivo

Multiple myeloma is a B cell malignancy. Recently, it has been demonstrated that bone marrow samples of patients with multiple myeloma display an enhanced angiogenesis. The mechanisms involved seem to be multiple and complex. We here demonstrate that the murine 5T multiple myeloma models are able to induce angiogenesis in vitro by using a rat aortic ring assay and in vivo by determining the microvessel density. The rat aortic rings cultured in 5T multiple myeloma conditioned medium exhibit a higher number of longer and more branched microvessels than the rings cultured in control medium. In bone marrow samples from 5T multiple myeloma diseased mice, a statistically significant increase of the microvessel density was observed when compared to bone marrow samples from age-matched controls. The angiogenic phenotype of both 5T multiple myeloma cells could be related, at least in part, to their capacity to produce vascular endothelial growth factor. These data clearly demonstrate that the 5T multiple myeloma models are good models to study angiogenesis in multiple myeloma and will allow to unravel the mechanisms of neovascularisation, as well as to test new putative inhibitors of angiogenesis