Cichoń’s diagram for uncountable cardinals

We develop a version of Cichoń’s diagram for cardinal invariants on the generalized Cantor space 2 κ or the generalized Baire space κ κ , where κ is an uncountable regular cardinal. For strongly inaccessible κ, many of the ZFC-results about the order relationship of the cardinal invariants which hold for ω generalize; for example, we obtain a natural generalization of the Bartoszyński–Raisonnier–Stern Theorem. We also prove a number of independence results, both with < κ-support iterations and κ-support iterations and products, showing that we consistently have strict inequality between some of the cardinal invariants

Improved physiological properties of gravity-enforced reassembled rat and human pancreatic pseudo-islets

Previously we demonstrated the superiority of small islets vs large islets in terms of function and survival after transplantation, and we generated reaggregated rat islets (pseudo-islets) of standardized small dimensions by the hanging-drop culture method (HDCM). The aim of this study was to generate human pseudo-islets by HDCM and to evaluate and compare the physiological properties of rat and human pseudo-islets. Isolated rat and human islets were dissociated into single cells and incubated for 6-14 days by HDCM. Newly formed pseudo-islets were analysed for dimensions, morphology, glucose-stimulated insulin secretion (GSIS) and total insulin content. The morphology of reaggregated human islets was similar to that of native islets, while rat pseudo-islets had a reduced content of α and δ cells. GSIS of small rat and human pseudo-islets (250 cells) was increased up to 4.0-fold (p < 0.01) and 2.5-fold (p < 0.001), respectively, when compared to their native counterparts. Human pseudo-islets showed a more pronounced first-phase insulin secretion as compared to intact islets. GSIS was inversely correlated to islet size, and small islets (250 cells) contained up to six-fold more insulin/cell than large islets (1500 cells). Tissue loss with this new technology could be reduced to 49.2 ± 1.5% in rat islets, as compared to the starting amount. With HDCM, pseudo-islets of standardized size with similar cellular composition and improved biological function can be generated, which compensates for tissue loss during production. Transplantation of small pseudo-islets may represent an attractive strategy to improve graft survival and function, due to better oxygen and nutrient supply during the phase of revascularization. Copyright © 2014 John Wiley & Sons, Ltd

Automated assessment of β-cell area and density per islet and patient using TMEM27 and BACE2 immunofluorescence staining in human pancreatic β-cells

In this study we aimed to establish an unbiased automatic quantification pipeline to assess islet specific features such as β-cell area and density per islet based on immunofluorescence stainings. To determine these parameters, the in vivo protein expression levels of TMEM27 and BACE2 in pancreatic islets of 32 patients with type 2 diabetes (T2D) and in 28 non-diabetic individuals (ND) were used as input for the automated pipeline. The output of the automated pipeline was first compared to a previously developed manual area scoring system which takes into account the intensity of the staining as well as the percentage of cells which are stained within an islet. The median TMEM27 and BACE2 area scores of all islets investigated per patient correlated significantly with the manual scoring and with the median area score of insulin. Furthermore, the median area scores of TMEM27, BACE2 and insulin calculated from all T2D were significantly lower compared to the one of all ND. TMEM27, BACE2, and insulin area scores correlated as well in each individual tissue specimen. Moreover, islet size determined by costaining of glucagon and either TMEM27 or BACE2 and β-cell density based either on TMEM27 or BACE2 positive cells correlated significantly. Finally, the TMEM27 area score showed a positive correlation with BMI in ND and an inverse pattern in T2D. In summary, automated quantification outperforms manual scoring by reducing time and individual bias. The simultaneous changes of TMEM27, BACE2, and insulin in the majority of the β-cells suggest that these proteins reflect the total number of functional insulin producing β-cells. Additionally, β-cell subpopulations may be identified which are positive for TMEM27, BACE2 or insulin only. Thus, the cumulative assessment of all three markers may provide further information about the real β-cell number per islet

Benutzerorientierte Software-Entwicklung Konzepte, Methoden und Vorgehen zur Benutzerbeteiligung

SIGLEAvailable from TIB Hannover: RR 3148(3) / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekBundesministerium fuer Forschung und Technologie (BMFT), Bonn (Germany)DEGerman