Peptiderger Einfluss auf 3T3-L1 Adipozyten

Bei der vorliegenden Arbeit handelt es sich um eine experimentelle Untersuchung zum Einfluss von zwei Ko-Transmittern des autonomen Nervensystems, Neuropeptid Y und dem Pituitary Adenylate Cyclase-activating Polypeptide (PACAP), auf den intrazellulären Kalziumspiegel und die Insulinsensitivität von 3T3-L1 Adipozyten. Mittels Polymerasekettenreaktion und Western Blot Analyse konnte die Expression des NPY-1 (Y1) Rezeptors als auch die der PACAP Rezeptoren PAC1 und VPAC2 nachgewiesen werden. Die Aktivierung des Y1 oder des PAC1 Rezeptors durch ihre Agonisten führte zur Erhöhung des intrazellulären Kalziumspiegels. Im Weiteren führte NPY nach Ko-Applikation mit Insulin zu einer abgeschwächten Insulinsensitivität der Adipozyten, da sowohl die insulin-stimulierte Translokation von Glukosetransporter 4 zur Zelloberfläche als auch die Glukoseaufnahme durch NPY abgeschwächt wurde. Dieser Effekt konnte als Y1 spezifisch beschrieben werden. Diese Ergebnisse gewähren somit neue Einblicke über den peptidergen Einfluss auf den Adipozytenstoffwechsel und erlauben Rückschlüsse über die Rolle des autonomen Nervensystems in der Entwicklung von Adipositas und Diabetes mellitus Typ 2

Powerful knowledge, transformations and the need for empirical studies across school subjects

In this article, we explore the concept of ’powerful knowledge’ which, from a curriculum studies perspective, refers to the aspects of content knowledge towards which teaching should be oriented. We then consider how the concept of ‘powerful knowledge’ can be developed and operationalized as a research framework within studies in subject-specific didactics across the curriculum by relating it to the analytical concept of ‘transformation’. Transformation is perceived in this case as an integrative process in which content knowledge is transformed into knowledge that is taught and learned through various transformation processes both outside and within the educational system. We argue that powerful knowledge cannot be identified based on the discipline alone, but needs to consider transformation processes and be empirically explored. A variety of theories and frameworks developed within the European research tradition of didactics are described as ways to study transformation processes related to powerful knowledge at different institutional levels as well as between different subjects and disciplines. A comparative research framework related to subject-specific education is proposed around three research questions

Synthesis and characterization of dicarboxymethyl cellulose

Associate Laboratory for Green Chemistry-LAQV which is financed by national funds from FCT/MCTES (UID/QUI/50006/2019). FCT, Portugal (ROTEIRO/0031/2013–PINFRA/22161/2016, co-financed by FEDER through COMPETE 2020, POCI, and PORL and FCT through PIDDAC).Synthesis of dicarboxymethyl cellulose (DCMC) under heterogeneous conditions was examined. Cellulose was etherified using sodium bromomalonate in isopropanol/water in the presence of NaOH. The reaction was performed with five different NaOH concentrations (5–30 w/v %) and the products were characterized by anion-exchange high-performance liquid chromatography (AE-HPLC), inductively coupled plasma atomic emission- (ICP-AES), Fourier transform infrared- (FTIR), and nuclear magnetic resonance (1D-/2D-NMR) spectroscopy. Adjusting the amount of NaOH resulted in increasing functionalization of the cellulose achieving an average degree of substitution (DS) between 0.05 and 0.51. Both ICP-AES and AE-HPLC gave comparable DS values. NMR spectroscopic analysis showed that etherification occurred preferably at O-6 and, to a certain extent, at the secondary positions depending on the reaction conditions. Graphic abstract: [Figure not available: see fulltext.].authorsversionpublishe

Elements of a design method – a basis for describing and evaluating design methods

open access articleMethod development is at the heart of design research as methods are a formalised way to express knowledge about how aspects of design could or should be done. However, assuring that methods are in fact used in industry has remained a challenge. Industry will only use methods that they can understand and that they feel will give them benefit reliably. To understand the challenges involved in adopting a method, the method needs to be seen in context: it does not exist in isolation but forms a part of an ecosystem of methods for tackling related design problems. A method depends on the knowledge and skills of the practitioners using it: while a description of a method is an artefact that is a formalisation of engineering knowledge, a method in use constitutes a socio-technical system depending on the interaction of human participants with each other as well as with the description of the method, representations of design information and, often, tools for carrying out the method's tasks. This paper argues that crucial factors in the adoption of methods include how well they are described and how convincingly they are evaluated. The description of a method should cover its core idea, the representations in which design information is described, the procedure to be followed, its intended use, and the tools it uses. The account of a method's intended use should cover its purpose, the situations or product types within its scope, its coverage of kinds of problems within its scope, its expected benefit, and conditions for its use. The different elements need to be evaluated separately as well as the method as an integrated whole. While verification and validation are important for some elements of methods, it is rarely possible to prove the validity of a method. Rather the developers of methods need to gather sufficient evidence that a method will work within a clearly articulated scope. Most design methods do not have binary success criteria, and their usefulness in practice depends as much on simplicity and usability as on the outcomes they produce. Evaluation should focus on how well they work, and how they can be customised and improved

Design of a Nanometric AlTi Additive for MgB2-Based Reactive Hydride Composites with Superior Kinetic Properties

Solid-state hydride compounds are a promising option for efficient and safe hydrogen-storage systems. Lithium reactive hydride composite system 2LiBH4 + MgH2/2LiH + MgB2 (Li-RHC) has been widely investigated owing to its high theoretical hydrogen-storage capacity and low calculated reaction enthalpy (11.5 wt % H2 and 45.9 kJ/mol H2). In this paper, a thorough investigation into the effect of the formation of nano-TiAl alloys on the hydrogen-storage properties of Li-RHC is presented. The additive 3TiCl3·AlCl3 is used as the nanoparticle precursor. For the investigated temperatures and hydrogen pressures, the addition of ∼5 wt % 3TiCl3·AlCl3 leads to hydrogenation/dehydrogenation times of only 30 min and a reversible hydrogen-storage capacity of 9.5 wt %. The material containing 3TiCl3·AlCl3 possesses superior hydrogen-storage properties in terms of rates and a stable hydrogen capacity during several hydrogenation/dehydrogenation cycles. These enhancements are attributed to an in situ nanostructure and a hexagonal AlTi3 phase observed by high-resolution transmission electron microscopy. This phase acts in a 2-fold manner, first promoting the nucleation of MgB2 upon dehydrogenation and second suppressing the formation of Li2B12H12 upon hydrogenation/dehydrogenation cycling.Fil: Le, Thi-Thu. Helmholtz Zentrum Geesthacht; AlemaniaFil: Pistidda, Claudio. Helmholtz Zentrum Geesthacht; AlemaniaFil: Puszkiel, Julián Atilio. Helmholtz Zentrum Geesthacht; Alemania. Comisión Nacional de Energía Atómica. Centro Atómico Bariloche; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte; ArgentinaFil: Castro Riglos, Maria Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte; Argentina. Helmholtz Zentrum Geesthacht; Alemania. Comisión Nacional de Energía Atómica. Centro Atómico Bariloche; ArgentinaFil: Karimi, Fahim. Helmholtz Zentrum Geesthacht; AlemaniaFil: Skibsted, Jørgen. University Aarhus; DinamarcaFil: Gharibdoust, Seyedhosein Payandeh. University Aarhus; DinamarcaFil: Richter, Bo. University Aarhus; DinamarcaFil: Emmler, Thomas. Helmholtz Zentrum Geesthacht; AlemaniaFil: Milanese, Chiara. Università di Pavia; ItaliaFil: Santoru, Antonio. Helmholtz Zentrum Geesthacht; AlemaniaFil: Hoell, Armin. Helmholtz Zentrum Berlin für Materialien und Energie; AlemaniaFil: Krumrey, Michael. Physikalisch Technische Bundesanstalt; AlemaniaFil: Gericke, Eike. Universität zu Berlin; AlemaniaFil: Akiba, Etsuo. Kyushu University; JapónFil: Jensen, Torben R.. University Aarhus; DinamarcaFil: Klassen, Thomas. Helmholtz Zentrum Geesthacht; Alemania. Helmut Schmidt University; AlemaniaFil: Dornheim, Martin. Helmholtz Zentrum Geesthacht; Alemani

Clinical efficacy of omalizumab in chronic spontaneous urticaria is associated with a reduction of FcεRI-positive cells in the skin

Background. Treatment with omalizumab, a humanized recombinant monoclonal anti-IgE antibody, results in clinical efficacy in patients with Chronic Spontaneous Urticaria (CSU). The mechanism of action of omalizumab in CSU has not been elucidated in detail. Objectives. To determine the effects of omalizumab on levels of high affinity IgE receptor-positive (FcεRI+) and IgE- positive (IgE+) dermal cells and blood basophils. Treatment efficacy and safety were also assessed. Study design. In a double-blind study, CSU patients aged 18‑75 years were randomized to receive 300 mg omalizumab (n=20) or placebo (n=10) subcutaneously every 4 weeks for 12 weeks. Changes in disease activity were assessed by use of the weekly Urticaria Activity Score (UAS7). Circulating IgE levels, basophil numbers and levels of expression of FcεRI+ and IgE+ cells in the skin and in blood basophils were determined. Results. Patients receiving omalizumab showed a significantly greater decrease in UAS7 compared with patients receiving placebo. At Week 12 the mean difference in UAS7 between treatment groups was -14.82 (p=0.0027), consistent with previous studies. Total IgE levels in serum were increased after omalizumab treatment and remained elevated up to Week 12. Free IgE levels decreased after omalizumab treatment. Mean levels of FcεRI+ skin cells in patients treated with omalizumab 300 mg were decreased at Week 12 compared with baseline in the dermis of both non-lesional and lesional skin, reaching levels comparable with those seen in healthy volunteers (HVs). There were no statistically significant changes in mean FcɛRI+ cell levels in the placebo group. Similar results were seen for changes in IgE+ cells, although the changes were not statistically significant. The level of peripheral blood basophils increased immediately after treatment start and returned to Baseline values after the follow-up period. The levels of FcεRI and IgE expression on peripheral blood basophils were rapidly reduced by omalizumab treatment up to Week 12. Conclusions. Treatment with omalizumab resulted in rapid clinical benefits in patients with CSU. Treatment with omalizumab was associated with reduction in FcɛRI+ and IgE+ basophils and intradermal cells

Nab: Measurement Principles, Apparatus and Uncertainties

The Nab collaboration will perform a precise measurement of 'a', the electron-neutrino correlation parameter, and 'b', the Fierz interference term in neutron beta decay, in the Fundamental Neutron Physics Beamline at the SNS, using a novel electric/magnetic field spectrometer and detector design. The experiment is aiming at the 10^{-3} accuracy level in (Delta a)/a, and will provide an independent measurement of lambda = G_A/G_V, the ratio of axial-vector to vector coupling constants of the nucleon. Nab also plans to perform the first ever measurement of 'b' in neutron decay, which will provide an independent limit on the tensor weak coupling.Comment: 12 pages, 6 figures, 1 table, talk presented at the International Workshop on Particle Physics with Slow Neutrons, Grenoble, 29-31 May 2008; to appear in Nucl. Instrum. Meth. in Physics Research

New measurement of the scattering cross section of slow neutrons on liquid parahydrogen from neutron transmission

Liquid hydrogen is a dense Bose fluid whose equilibrium properties are both calculable from first principles using various theoretical approaches and of interest for the understanding of a wide range of questions in many body physics. Unfortunately, the pair correlation function $g(r)$ inferred from neutron scattering measurements of the differential cross section $d\sigma \over d\Omega$ from different measurements reported in the literature are inconsistent. We have measured the energy dependence of the total cross section and the scattering cross section for slow neutrons with energies between 0.43~meV and 16.1~meV on liquid hydrogen at 15.6~K (which is dominated by the parahydrogen component) using neutron transmission measurements on the hydrogen target of the NPDGamma collaboration at the Spallation Neutron Source at Oak Ridge National Laboratory. The relationship between the neutron transmission measurement we perform and the total cross section is unambiguous, and the energy range accesses length scales where the pair correlation function is rapidly varying. At 1~meV our measurement is a factor of 3 below the data from previous work. We present evidence that these previous measurements of the hydrogen cross section, which assumed that the equilibrium value for the ratio of orthohydrogen and parahydrogen has been reached in the target liquid, were in fact contaminated with an extra non-equilibrium component of orthohydrogen. Liquid parahydrogen is also a widely-used neutron moderator medium, and an accurate knowledge of its slow neutron cross section is essential for the design and optimization of intense slow neutron sources. We describe our measurements and compare them with previous work.Comment: Edited for submission to Physical Review

Di-(2-Ethylhexyl)-Phthalate (DEHP) Causes Impaired Adipocyte Function and Alters Serum Metabolites

Di-(2-ethylhexyl)-phthalate (DEHP), an ubiquitous environmental contaminant, has been shown to cause adverse effects on glucose homeostasis and insulin sensitivity in epidemiological studies, but the underlying mechanisms are still unknown. We therefore tested the hypothesis that chronic DEHP exposure causes impaired insulin sensitivity, affects body weight, adipose tissue (AT) function and circulating metabolic parameters of obesity resistant 129S6 mice in vivo. An obesity-resistant mouse model was chosen to reduce a potential obesity bias of DEHP effects on metabolic parameters and AT function. The metabolic effects of 10-weeks exposure to DEHP were tested by insulin tolerance tests and quantitative assessment of 183 metabolites in mice. Furthermore, 3T3-L1 cells were cultured with DEHP for two days, differentiated into mature adipocytes in which the effects on insulin stimulated glucose and palmitate uptake, lipid content as well as on mRNA/protein expression of key adipocyte genes were investigated.We observed in female mice that DEHP treatment causes enhanced weight gain, fat mass, impaired insulin tolerance, changes in circulating adiponectin and adipose tissue Pparg, adiponectin and estrogen expression. Serum metabolomics indicated a general increase in phospholipid and carnitine concentrations. In vitro, DEHP treatment increases the proliferation rate and alters glucose uptake in adipocytes. Taken together, DEHP has significant effects on adipose tissue (AT) function and alters specific serum metabolites. Although, DEHP treatment led to significantly impaired insulin tolerance, it did not affect glucose tolerance, HOMA-IR, fasting glucose, insulin or triglyceride serum concentrations. This may suggest that DEHP treatment does not cause impaired glucose metabolism at the whole body level