We have successfully developed an efficient approach to 3,4-disubstituted £\,£]-unsaturated £_-lactams from glutarimide, and proved to be applicable for the synthesis of hydrocinchonine and hydrocinchonidine.

Androgen has been shown to stimulate proliferation of osteoblast-like MC3T3-E1 cells. However, the molecular mechanism responsible for this effect remains to be elucidated. In the present study we demonstrate herein the non-genomic effect of androgen on osteoblast-like MC3T3-E1 cells involving activation of a PI(3)K/Akt signaling pathway and stimulating proliferation. In studies of steroids signaling, 5a-dihydrotestosterone (DHT), testosterone and 17b-estradiol but not dexamethasone or progesterone induced a rapid and transient phosphorylation of Akt in MC3T3-E1 cells. The androgen-induced Akt activation reached to the climax after 15 min and gradually diminished to baseline after 60 min. This induction of androgen was unaffected by actinomycin D and was specifically blocked by androgen receptor (AR) antagonist hydroxyflutamide (HF) or transfection of siRNA-AR. Treatment of MC3T3-E1 cells with PI(3)K inhibitor LY294002 or transfection with kinase-deficient Akt blocked androgen-induced cells proliferation. Moreover, androgen-induced activation of Akt was abolished by inhibitors of Src kinase, Gi-protein and phospholipase C showing the involvement of these effectors in androgen signaling pathway. Further, androgen-induced activation of Akt was dependent on intracellular calcium as shown by the effect of EGTA and intracellular calcium chelator BAPTA/AM. Fluorescence microscopy showed translocation of phospho-Akt from cytosol into nucleus after androgen treatment but no change in the subcellular distribution of phospho-Akt when HF or LY294002 pretreatment was administered to the cells. These results strongly suggest that phosphorylation of Akt in osteoblast cells is mediated by androgen receptor and the androgen-induced translocation of Akt is an important step in the androgen/AR signaling pathway that mediates osteoblast cells proliferation.

In MCF7 and T47D cells cotreated with 1 nM 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) plus 0.1-10 μM 3’,4’-dimethoxy flavone (DMF), there was a concentration-dependent decrease in the TCDD-induced ethoxyresorufin O-deethylase (EROD) activity. Gel mobility shift assays showed that 3’,4’-DMF inhibited TCDD-induced aryl hydrocarbon receptor (AhR) transformation in rat liver cytosol and blocked TCDD-induced formation of the nuclear AhR complex in MCF7 and T47D cells. The antiestrogenic activity of TCDD in estrogen-induced transactivation assays in MCF7 cells was reversed by 3’,4’-DMF, confirming the AhR antagonist activity of this compound in breast cancer cells. Cotreatment of T47D and MCF7 cells with TCDD and 10 μM resveratrol inhibited induction of CYP1A1 mRNA and EROD activity. Resveratrol did not inhibit TCDD-induced AhR transformation and reporter gene activity. Actinomycin D chase experiments in T47D cells showed that the mechanism of inhibition of CYP1A1 mRNA and EROD activity is due to an increased rate of CYP1A1 mRNA degradation, suggesting that resveratrol inhibits CYP1A1 via an AhR-independent post-transcriptional pathway. Vitamin D receptor-interacting protein 150 (DRIP150) coactivated estrogen receptor α (ER α)-mediated transactivation and the response was AF2-dependent in ZR75 breast cancer cells. C-and N-terminal NR-boxes (amino acids 1186-1182 and 73-69, respectively) were not necessary for coactivation of ERα. Analysis of DRIP150 deletion mutants identified a 23 amino acid sequence (811-789) required for coactivation. The 23 amino acid contained two regions at amino acids 789-794 and 795-804 which resembled α-helical motifs identified in Lanuguinosa lipase/histamine N-methyl transferase and hepatocyte nuclear factor 1, respectively. A squelching assay using specific point mutations within each α-helix showed that the NIFSEVRVYN (795-804) region was the critical sequence required for the coactivator activity of DRIP150.

This study examines the carcinogenic effect of HZE radiation and protective effects of different types of diets against colon carcinogenesis in a rat model. The effect of HZE radiation on health state and colon cancer development was evaluated. HZE radiation was found to suppress food consumption (P<0.0001) leading to lower body weight gain of irradiated rats when compared to the non-irradiated rats (P<0.05). The animals exposed to HZE radiation were found to start dying and/or getting pathologies 11 weeks earlier and at the end of the study had morbidity/mortality rate 14.2% higher (P=0.0005) than non-irradiated rats. There was no significant effect of HZE radiation on colon cancer incidence. The effects of dietary fibers and oils on health state and colon carcinogenesis were evaluated. Morbidity/mortality was found to be delayed in rats fed with pectinbased diets when compared to cellulose-based diet, regardless of radiation treatment. Similarly, fish oil was found to beneficially affect health of the experimental animals when compared to corn oil. Ten- and twenty-week delayed morbidity/mortality for irradiated and non-irradiated groups, respectively, was observed for rats fed with fish oil-based diets when compared to corn oil-based diets. Fish oil was also found to significantly reduce colon tumor incidence and multiplicity in non-irradiated rats (P<0.05). A similar trend was observed for the irradiated animals. No significant effect of fiber on colon cancer incidence was found. Finally, the effect of diets on general health and colon cancer development was investigated. Rats fed with corn oil/cellulose diet started dying and/or getting a disease earlier than rats fed with other diets, regardless of radiation treatment. The effect of diet on colon cancer development was found to depend on radiation treatment. Thus, in the absence of radiation treatment fish oil/cellulose was found to significantly reduce tumor incidence and multiplicity when compared to corn oil/pectin diet (P<0.05). In the presence of radiation treatment fish oil/pectin was found to lower the values of tumor incidence and tumor multiplicity, though the data obtained were not significant.

To examine how dietary n-3 polyunsaturated fatty acids affect Th2 cell development, female C57BL/6 mice were fed a washout corn oil (CO) diet for 1 wk followed by 2 wk of either the same CO diet or a fish oil (FO) diet. CD4+ T cells were isolated from spleens and cultured under both neutral (anti-CD3 and phorbol myristate acetate (PMA)) and Th2 polarizing conditions (anti-CD3 and PMA, in presence of rIL-4, rIL-2, and anti-IFN-γ) in the presence of homologous mouse serum (HMS) or fetal bovine serum (FBS) for 2 d. Dietary n-3 PUFA significantly enhanced Th2 cell development and suppressed Th1 development under neutral conditions as assessed by intracellular cytokine staining for IL-4 and IFN-γ as the two prototypic Th2 and Th1 cytokines, respectively. However, under Th2 polarizing conditions, while the suppression of Th1 cells was maintained in FO-fed mice, no dietary effect was observed in Th2 cells. Dietary FO increased the Th2/Th1 ratio under both neutral and Th2 polarizing conditions with HMS in the cultures. To examine the effect of dietary n-3 PUFA on Th1 development, DO11.10 Rag2-/- mice expressing transgenic T cell receptor specific for ovalbumin (OVA) peptide were used. CD4+ T cells were isolated from spleens and lymph nodes and stimulated with ovalbumin (OVA) peptide and irradiated BALB/c splenocytes in the presence of rIL-12, anti-IL-4, and rIL-2 in HMS for 2d. Cells were expanded for another 3 d in the presence of rIL-2 and rIL-12. Dietary n-3 PUFA did not affect Th1 differentiation as assessed by the proportion of IFN-γ+, IL-4- T cells in the cultures, but suppressed rIL-2 induced expansion. The suppressed expansion was due to suppressed proliferation (p<0.05). In vivo expansion of antigen-specific T cells was visualized by flow cytometric analysis of CFSE-positive transgenic T cells. Dietary n-3 PUFA did not appear to affect antigen-induced CD4+ T cell cycle progression in vivo. Overall, these results suggest dietary n-3 PUFA have no direct effect on Th2 cell development but do directly suppress Th1 cell development following both mitogenic and antigenic stimulation in vitro.

In architectural and sculptural practice, the eventual goal is constructing the shapes that have been designed. Due to fabrication considerations, shapes with planar faces are in demand for these practices. In this thesis, a novel computational modeling approach to design constructible shapes is introduced. This method guarantees that the resulting shapes are planar meshes with 3-valence vertices, which can always be physically constructed using planar or developable materials such as glass, sheet metal or plywood. The method introduced is inspired by the traditional sculpture and is based on the idea of carving a mesh by using slicing planes. The process of determining the slicing planes can either be interactive or automated. A framework is developed which allows user to sculpt shapes by using the in- teractive and automated processes. The framework allows user to cut a source mesh based on its edges, faces or vertices. The user can sculpt various kinds of developable surfaces by cutting the parallel edges of the mesh. The user can also introduce in- teresting conical patterns by cutting dierent vertex, edge, face combinations of the mesh.

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<p>Titel</p><p>Skriv inte av, testa nedskrivning! En fallstudie om att säkerställa ett nedskrivningsbehov av goodwill</p><p>Bakgrund</p><p>Företagsförvärv har blivit allt mer vanligt förekommande. Goodwill uppkommer då ett företags verkliga värde är mindre än vad som betalas. Goodwillvärdet skrevs förr av planenligt, men enligt de nya reglerna ska nu ett nedskrivningstest ske minst en gång per år. Det sker genom att ta fram ett återvinningsvärde, som är det högsta av en kassagenererande enhets nettoförsäljningsvärde och nyttjandevärde.</p><p>Syfte</p><p>Syftet med uppsatsen är att beskriva hur kassagenererande enheter värderas enligt metoderna i IFRS 3/IAS 36, samt förklara svårigheter/möjligheter och vilka överväganden som metoderna innebär i två praktiska exempel.</p><p>Metod</p><p>I vår uppsats har vi utgått från ett positivistiskt synsätt och tillämpat en kvalitativ fallstudie av NIBE och ProfilGruppen. Vår uppsats har sin utgångspunkt i den abduktiva forskningsansatsen. Vi har för avsikt att beskriva och förklara nedskrivningstestet, vilket innebär att undersökningen är deskriptiv. Vi har intervjuat Leif Gustavsson, ekonomidirektör på NIBE, och Ulrika Svensson, redovisningschef på ProfilGruppen, samt tagit del av deras årsredovisningar.</p><p>Slutsats</p><p>Våra fallföretag använder sig av nyttjandevärde vid nedskrivningstestet. Ett av företagen använder sig av reala kassaflöden med en nominell diskonteringsfaktor, vilket resulterar i att nyttjandevärdet blir för lågt. Tidsperioderna företagen använder sig av skiljer sig från rekommendationerna, som förespråkar fem år. Studien har visat att det finns möjlighet till justering i poster för att uppnå önskvärt återvinningsvärde. Båda företagen föredrar det gamla sättet med avskrivning av goodwill, då metoden är enkel och förutsägbar.</p><p>Förslag till fortsatt forskning</p><p>Granska om de nya reglerna har fått önskad effekt om rättvisande värdering och redovisning av goodwill. Undersöka om det finns företag som använder nettoförsäljningsvärdet vid värderingen och hur en sådan praktiskt tillämpas. Genomföra ytterligare studier för att se om fler företag blandar reala och nominella termer vid beräkning av nyttjandevärdet.</p>

Vorstellung der R/3-Architektur und Einsatz des Linux-Frontends am Arbeitsplatz.

Fachhochschule (FH), Diplomarbeit--Trier, 2006. / Nebent.: SAP Web DYNPRO versus IBM Portlets.