Energy efficient room illumination by the redirection of sunlight : new micro structured components

Paper presented to the 3rd Southern African Solar Energy Conference, South Africa, 11-13 May, 2015.Non tracking daylight systems, which redirect the light from solar altitudes between 15° and 65° deep into rooms without causing glare effects, have been applied successfully in several office buildings recently. These systems are based on specially shaped polymer profiles which are inserted in double glass windows and which are commercialized under the label LUMITOP. Based on these macro structured systems, fixed in the upper area of windows above eyelevel, advanced solutions using micro structured components will be reported. Main objective of this new development is the reduction of material input (e.g. PMMA) and production costs. Additionally, the optical properties and redirection performance of the existing system should be improved. First, ray tracing calculations have been carried out to identify optimum solutions for micro structured components capable of redirecting daylight with high and almost homogeneous efficiency over the relevant angular range of solar altitudes and not showing colour effects. The simulation results show, that by using a combination of micro lenses and micro prisms an almost homogeneous sunlight redirection of about 70% is achieved in the angular range of solar altitudes between 25° and 65°. These results could be confirmed by prototypes fabricated in the highly transparent silicone polymer PDMS. Suitable industrial production processes for large area panels (1400 mm x 400mm x 4mm) are hot embossing in thermoplastic materials like PMMA and UV-embossing in special UV-curing resins. Both processes are under development and the status of the development will be reported.cf201

Designer Lipid-Like Peptides: A Class of Detergents for Studying Functional Olfactory Receptors Using Commercial Cell-Free Systems

A crucial bottleneck in membrane protein studies, particularly G-protein coupled receptors, is the notorious difficulty of finding an optimal detergent that can solubilize them and maintain their stability and function. Here we report rapid production of 12 unique mammalian olfactory receptors using short designer lipid-like peptides as detergents. The peptides were able to solubilize and stabilize each receptor. Circular dichroism showed that the purified olfactory receptors had alpha-helical secondary structures. Microscale thermophoresis suggested that the receptors were functional and bound their odorants. Blot intensity measurements indicated that milligram quantities of each olfactory receptor could be produced with at least one peptide detergent. The peptide detergents' capability was comparable to that of the detergent Brij-35. The ability of 10 peptide detergents to functionally solubilize 12 olfactory receptors demonstrates their usefulness as a new class of detergents for olfactory receptors, and possibly other G-protein coupled receptors and membrane proteins.United States. Defense Advanced Research Projects Agency (DARPA-HR0011-09-C-0012)Massachusetts Institute of Technology. Undergraduate Research Opportunities Progra

Clinical and Functional Characterization of a Patient Carrying a Compound Heterozygous Pericentrin Mutation and a Heterozygous IGF1 Receptor Mutation

Intrauterine and postnatal longitudinal growth is controlled by a strong genetic component that regulates a complex network of endocrine factors integrating them with cellular proliferation, differentiation and apoptotic processes in target tissues, particularly the growth centers of the long bones. Here we report on a patient born small for gestational age (SGA) with severe, proportionate postnatal growth retardation, discreet signs of skeletal dysplasia, microcephaly and moyamoya disease. Initial genetic evaluation revealed a novel heterozygous IGF1R p.Leu1361Arg mutation affecting a highly conserved residue with the insulin-like growth factor type 1 receptor suggestive for a disturbance within the somatotropic axis. However, because the mutation did not co-segregate with the phenotype and functional characterization did not reveal an obvious impairment of the ligand depending major IGF1R signaling capabilities a second-site mutation was assumed. Mutational screening of components of the somatotropic axis, constituents of the IGF signaling system and factors involved in cellular proliferation, which are described or suggested to provoke syndromic dwarfism phenotypes, was performed. Two compound heterozygous PCNT mutations (p.[Arg585X];[Glu1774X]) were identified leading to the specification of the diagnosis to MOPD II. These investigations underline the need for careful assessment of all available information to derive a firm diagnosis from a sequence aberration

Liposome-Mediated Cellular Delivery of Active gp91phox

International audienceBACKGROUND: Gp91(phox) is a transmembrane protein and the catalytic core of the NADPH oxidase complex of neutrophils. Lack of this protein causes chronic granulomatous disease (CGD), a rare genetic disorder characterized by severe and recurrent infections due to the incapacity of phagocytes to kill microorganisms. METHODOLOGY: Here we optimize a prokaryotic cell-free expression system to produce integral mammalian membrane proteins. CONCLUSIONS: Using this system, we over-express truncated forms of the gp91(phox) protein under soluble form in the presence of detergents or lipids resulting in active proteins with a "native-like" conformation. All the proteins exhibit diaphorase activity in the presence of cytosolic factors (p67(phox), p47(phox), p40(phox) and Rac) and arachidonic acid. We also produce proteoliposomes containing gp91(phox) protein and demonstrate that these proteins exhibit activities similar to their cellular counterpart. The proteoliposomes induce rapid cellular delivery and relocation of recombinant gp91(phox) proteins to the plasma membrane. Our data support the concept of cell-free expression technology for producing recombinant proteoliposomes and their use for functional and structural studies or protein therapy by complementing deficient cells in gp91(phox) protein

Novel Regulatory Mechanisms for Generation of the Soluble Leptin Receptor: Implications for Leptin Action

The adipokine leptin realizes signal transduction via four different membrane-anchored leptin receptor (Ob-R) isoforms in humans. However, the amount of functionally active Ob-R is affected by constitutive shedding of the extracellular domain via a so far unknown mechanism. The product of the cleavage process the so-called soluble leptin receptor (sOb-R) is the main binding protein for leptin in human blood and modulates its bioavailability. sOb-R levels are differentially regulated in metabolic disorders like type 1 diabetes mellitus or obesity and can, therefore, enhance or reduce leptin sensitivity.To describe mechanisms of Ob-R cleavage and to investigate the functional significance of differential sOb-R levels we established a model of HEK293 cells transiently transfected with different human Ob-R isoforms. Using siRNA knockdown experiments we identified ADAM10 (A Disintegrin And Metalloproteinase 10) as a major protease for constitutive and activated Ob-R cleavage. Additionally, the induction of lipotoxicity and apoptosis led to enhanced shedding shown by increased levels of the soluble leptin receptor (sOb-R) in cell supernatants. Conversely, high leptin concentrations and ER stress reduced sOb-R levels. Decreased amounts of sOb-R due to ER stress were accompanied by impaired leptin signaling and reduced leptin binding.Lipotoxicity and apoptosis increased Ob-R cleavage via ADAM10-dependent mechanisms. In contrast high leptin levels and ER stress led to reduced sOb-R levels. While increased sOb-R concentrations seem to directly block leptin action, reduced amounts of sOb-R may reflect decreased membrane expression of Ob-R. These findings could explain changes of leptin sensitivity which are associated with variations of serum sOb-R levels in metabolic diseases

The eukaryotic CO2-concentrating organelle is liquid-like and exhibits dynamic reorganization

Approximately 30%–40% of global CO 2 fixation occurs inside a non-membrane-bound organelle called the pyrenoid, which is found within the chloroplasts of most eukaryotic algae. The pyrenoid matrix is densely packed with the CO 2-fixing enzyme Rubisco and is thought to be a crystalline or amorphous solid. Here, we show that the pyrenoid matrix of the unicellular alga Chlamydomonas reinhardtii is not crystalline but behaves as a liquid that dissolves and condenses during cell division. Furthermore, we show that new pyrenoids are formed both by fission and de novo assembly. Our modeling predicts the existence of a “magic number” effect associated with special, highly stable heterocomplexes that influences phase separation in liquid-like organelles. This view of the pyrenoid matrix as a phase-separated compartment provides a paradigm for understanding its structure, biogenesis, and regulation. More broadly, our findings expand our understanding of the principles that govern the architecture and inheritance of liquid-like organelles

Joint recommendations on cost calculation and estimation in paediatric clinical trials

The conduct of clinical trials in paediatrics is essential to improve drug therapy in children. In Europe, paediatric clinical trials have been supported by the European Paediatric Regulation since 2007, but there is still a great need for high-quality clinical trials.The personnel and time required to conduct clinical trials in accordance with EU Regulations 536/2014 and 745/2017 is considerably higher compared to other studies, such as observational studies. It is important that this additional workload for the trial centre is fully compensated, also taking into account EU state aid rules. In paediatric trials, it is necessary to take into account the special requirements of paediatric and adolescent medicine when calculating the additional costs. Within the framework of the pan-European paediatric study network c4c/GermanNetPaeT, a working group dealt with specific aspects of cost calculation in order to support paediatric study centres in internal cost calculation as well as in the subsequent preparation of financing requirements for industrial sponsors or public funders. In several workshops the working group developed a cost calculation template with the content derived from the "Joint recommendations for a total services account as a factor in simplifying contracts" of the Deutsche Hochschulmedizin (DHM, German University Medicine), the Netzwerk der Koordinierungszentren für Klinische Studien (KKS Network, Network of Coordinating Centres for Clinical Trials) and the Verband Forschender Arzneimittelhersteller (vfa, German Association of Research-Based Pharmaceutical Companies).By estimating the specific time required for measures and investigations as part of a sample study, the background to the increased time required was discussed and a list with aspects to be considered for cost calculation was compiled together with the study centres. The paediatrics-specific aspects mentioned in detail are intended to increase understanding of the particular problem of higher costs for clinical trials involving children and adolescents and the need for correspondingly appropriate remuneration. This transparent and comprehensible presentation of the higher financial requirements for both the study centres and the financial supporters is intended to promote the high-quality conduct of clinical trials in paediatric study centres in the long term.Die Durchführung von klinischen Prüfungen in der Pädiatrie ist essentiell für die Verbesserung der Arzneimitteltherapie bei Kindern. In Europa werden pädiatrische klinische Prüfungen seit 2007 durch die European Paediatric Regulation gefördert; trotzdem besteht nach wie vor ein hoher Bedarf an qualitativ hochwertigen klinischen Studien.Der personelle und zeitliche Aufwand bei der Durchführung von klinischen Prüfungen entsprechend den EU-Verordnungen 536/2014 und 745/2017 ist im Vergleich zu anderen Studien, wie z.B. Beobachtungsstudien, erheblich größer. Es ist wichtig, dass dieser Mehraufwand des Prüfzentrums auch unter Berücksichtigung des EU-Beihilferechts vollkostendeckend vergütet wird. Bei pädiatrischen Studien ist es bei der Kostenermittlung des Mehraufwands notwendig, die besonderen Anforderungen der Kinder- und Jugendmedizin zu berücksichtigen. Im Rahmen des paneuropäischen pädiatrischen Studiennetzwerks c4c/GermanNetPaeT beschäftigte sich eine Arbeitsgruppe mit spezifischen Aspekten der Kostenkalkulation, um pädiatrische Studienzentren bei der internen Kostenermittlung ebenso wie nachfolgend auch bei der Erstellung des Finanzierungsbedarfes für industrielle Sponsoren oder öffentliche Förderer zu unterstützen. In Workshops erarbeitete die Arbeitsgruppe ein Kostenkalkulationstemplate, welches sich inhaltlich von den "Gemeinsamen Empfehlungen zur Erstellung einer Gesamtleistungsrechnung" von Deutscher Hochschulmedizin, dem Netzwerk der Koordinierungszentren für Klinische Studien (KKS-Netzwerk) und dem Verband Forschender Arzneimittelhersteller (vfa) ableitet.Durch die Abschätzung des konkreten Zeitbedarfs für Maßnahmen und Untersuchungen im Rahmen einer Beispielstudie wurden die Hintergründe des erhöhten Zeitbedarfs erörtert und zusammen mit den Studienzentren eine Liste mit Hinweisen für die Kostenkalkulation erstellt. Die im Detail benannten Pädiatrie-spezifischen Aspekte sollen das Verständnis für die besondere Problematik höherer Kosten für klinischen Prüfungen mit Kindern und Jugendlichen und die Notwendigkeit einer dementsprechend angemessenen Vergütung erhöhen. Durch diese transparente und nachvollziehbare Darstellung der höheren Finanzbedarfe sowohl für die Studienzentren als auch die finanziellen Unterstützer soll langfristig die qualitativ hochwertige Durchführung von klinischen Prüfungen in pädiatrischen Studienzentren gefördert werden