266 research outputs found
Reliable, optimised power transformers with heat recovery for urban areas
A project in the heart of London interconnects innovative transformer technologies to add value for the neighbourhood by delivering power and heat at the same time. Proven at 400 kV/240 MVA, the technology of combining ester insulation and heat recovery devices could be adopted in smaller transformers realizing significant cost saving and carbon footprint improvements
Dysregulated Expression of Glycolipids in Tumor Cells: From Negative Modulator of Anti-tumor Immunity to Promising Targets for Developing Therapeutic Agents
Glycolipids are complex molecules consisting of a ceramide lipid moiety linked to a glycan chain of variable length and structure. Among these are found the gangliosides, which are sialylated glycolipids ubiquitously distributed on the outer layer of vertebrate plasma membranes. Changes in the expression of certain species of gangliosides have been described to occur during cell proliferation, differentiation and ontogenesis. However, the aberrant and elevated expression of gangliosides has been also observed in different types of cancer cells, thereby promoting tumor survival. Moreover, gangliosides are actively released from the membrane of tumor cells, having a strong impact on impairing anti-tumor immunity. Beyond the undesirable effects of gangliosides in cancer cells, a substantial number of cancer immunotherapies have been developed in recent years that have used gangliosides as the main target. This has resulted in successful immune cell- or antibody-responses against glycolipids, with promising results having been obtained in clinical trials. In this review, we provide a general overview on the metabolism of glycolipids, both in normal and tumor cells, as well as examining glycolipid-mediated immune modulation and the main successes achieved in immunotherapies using gangliosides as molecular targets
Etanercept Treatment in Children With New-Onset Type 1 Diabetes: Pilot randomized, placebo-controlled, double-blind study
Pancreatic β-Cell Death in Response to Pro-Inflammatory Cytokines Is Distinct from Genuine Apoptosis
A reduction in functional β-cell mass leads to both major forms of diabetes; pro-inflammatory cytokines, such as interleukin-1beta (IL-1β) and gamma-interferon (γ-IFN), activate signaling pathways that direct pancreatic β-cell death and dysfunction. However, the molecular mechanism of β-cell death in this context is not well understood. In this report, we tested the hypothesis that individual cellular death pathways display characteristic phenotypes that allow them to be distinguished by the precise biochemical and metabolic responses that occur during stimulus-specific initiation. Using 832/13 and INS-1E rat insulinoma cells and isolated rat islets, we provide evidence that apoptosis is unlikely to be the primary pathway underlying β-cell death in response to IL-1β+γ-IFN. This conclusion was reached via the experimental results of several different interdisciplinary strategies, which included: 1) tandem mass spectrometry to delineate the metabolic differences between IL-1β+γ-IFN exposure versus apoptotic induction by camptothecin and 2) pharmacological and molecular interference with either NF-κB activity or apoptosome formation. These approaches provided clear distinctions in cell death pathways initiated by pro-inflammatory cytokines and bona fide inducers of apoptosis. Collectively, the results reported herein demonstrate that pancreatic β-cells undergo apoptosis in response to camptothecin or staurosporine, but not pro-inflammatory cytokines
Creating an original picture book for preschool children
Izdelava izvirne slikanice za predšolske otroke je naslov magistrskega dela, ki vsebuje teoretična izhodišča na podlagi raziskovanja različnih strokovnjakov iz literarnega področja in likovne umetnosti. Izmed književne literature za otroke so podrobneje opredeljeni definicija slikanice in elementi, ki jih vsebuje. Prav tako je opisana slikanica s poudarkom na kakovostni ilustraciji.
V praktičnem delu, ki je narejen na podlagi sinteze teoretičnih spoznanj, je prikazan postopek izdelave izvirne slikanice za predšolske otroke. Besedilo z naslovom Rojstnodnevna želja je napisala Rebeka Govedič, ilustrirala Laura Pukel. Govedič je diplomirala na smeri predšolska vzgoja PEF UM z diplomskim delom Razvijanje bralne pismenosti predšolskih otrok na podlagi izvirne slikanice. Pri vizualni podobi slikanice, ki je avtorsko delo, je bilo treba upoštevati elemente parabesedila (naslovnica, notranja naslovnica, vezni listi) in knjižnega vložka. Vsebinski del ilustracij predstavlja potek dogodkov, ki so opisani v zgodbi, prav tako so ilustracije analizirane na podlagi vsebinske upodobitve ob upoštevanih likovno-teoretičnih zakonitosti ter razumevanju interakcije med besedilom in ilustracijami.This master\u27s thesis explores the creation of an original picture book for preschool children, grounded in theoretical foundations drawn from research by experts in literature and visual arts. It delves into the definition of a picture book within the realm of children\u27s literature, outlining its key elements and emphasizing the importance of high-quality illustration.
The practical component builds upon these theoretical insights, presenting the process of creating an original picture book for preschool children. The text, titled Rojstnodnevna želja (The Birthday Wish), was written by Rebeka Govedič and illustrated by Laura Pukel. Govedič, a graduate in preschool education from the Faculty of Education, University of Maribor, developed the text as part of her thesis, Developing reading literacy of preschool children through creating an original picture book.
The visual design of the picture book, which constitutes my own work, required careful attention to paratextual elements such as the cover, inner title page, endpapers, and book insert. The illustrations reflect the narrative flow of the story and are analyzed in terms of their content, artistic-theoretical principles, and the interplay between text and imagery. This analysis also considers how visual and textual elements together enhance the reader\u27s understanding of the story
Interleukin-1 Inhibits Glucose-Modulated Insulin and Glucagon Secretion in Rat Islet Monolayer Cultures*
Destruction of Rat Islet Cell Monolayers by Cytokines: Synergistic Interactions of Interferon-γ, Tumor Necrosis Factor, Lymphotoxin, and Interleukin 1
An assay was developed to detect the cytotoxic effects of cytokines on rat pancreatic islet cells in monolayer culture. Cell lysis was detected by a 51Cr-release assay after 4 days of incubation with various cytokines. When tested alone, murine (rat and mouse) interferon-γ (mIFN-γ) produced a small dose-dependent lysis of islet cells; human IFN-γ, mouse IFN-α/β, interleukins 1 and 2 (IL-1 and IL-2), tumor necrosis factor (TNF), and lymphotoxin (LT) were inactive. When added together, the following combinations of cytokines showed synergistic cytotoxic effects: TNF (or LT) plus IL-1, TNF (or LT) plus mIFN-γ, and IL-1 plus mIFN-γ. These results indicate that the cytokine products of mononuclear cells of the immune system, IFN-γ, TNF, LT, and IL-1 have strong synergistic cytotoxic effects on islet cells and therefore may act as direct chemical mediators of islet β-cell destruction in type I (insulin-dependent) diabetes.</jats:p
Interleukin 2 Activates BB/W Diabetic Rat Lymphoid Cells Cytotoxic to Islet Cells
We compared the cytotoxic effects to islet cells of lymphoid cells from diabetic and diabetes-resistant (DR) BioBreeding/Worcester (BB/W) rats with a 51Cr-release assay to detect lysis of normal rat islet cells. Splenic lymphoid cells from diabetic rats were more cytotoxic to islet cells (11.3 ± 3.8%) than were lymphoid cells from DR rats (4.0 ± 2.6%). This difference was amplified by incubating the lymphoid cells for 20 h with 5 μg/ml concanavalin A (ConA); islet cell lysis was 39.3 ± 4.5% by ConA-activated diabetic cells and 9.6 ± 2.7% by ConA-activated DR cells. The cytotoxic lymphoid cells were identified as natural killer (NK) cells, because treatment of diabetic lymphoid cells with anti-asialo GM1 serum and complement selectively removed a monoclonal antibody-defined subset of NK cells (OX8+), and the NK-depleted lymphoid cells were not cytotoxic to either islet or NK-sensitive YAC-1 cells, even after culture with ConA. Of several lymphokine products of ConA-stimulated lymphoid cells, interleukin 2 (IL-2), but not interleukin 1 or interferon-γ, significantly activated splenic lymphoid cells cytotoxic to islet cells, and the lymphoid cells from diabetic rats were more sensitive to IL-2 (3 U/ml) than were the cells from DR rats (30 U/ml). This study reveals the presence of ConA- and IL-2-responsive islet cytotoxic NK cells in the diabetic BB/W rat and suggests that IL-2 activation of NK cells may contribute to islet β-cell destruction and diabetes in this animal.</jats:p
- …
