Human complement factor H

We isolated cDNA clones coding for the functionally important tryptic N-terminal38- kDa fragment of human complement control protein factor H using polyclonal and monoclonal antibodies to screen a human liver cDNA library cloned in a bacterial expression vector, PEX-1. By testing the reactivity of antibodies specific for the recombinant proteins produced by individual clones with proteolytic fragments of serum H the exact position of these cDNA clones within H was mapped. One clone, H-19, coding for the 38-kDa fragment of H was sequenced and found to code for 289 amino acids derived from the 38-kDa N-terminal fragment as well as for the first 108 amino acids belonging to the complementary 142-kDa tryptic fragment. The derived protein sequence could be arranged in 6 highly homologous repeats of about 60 amino acids each, the homology between the repeats being determined by the characteristic position of cysteine, proline, glycine, tyrosine and tryptophane residues. The region coding for the epitope recognized by one of our monoclonal antibodies was localized by subcloning restriction fragments of H-19 into the expression plasmid and testing for the expression of this epitope

CLONING OF THE 1.4-kb mRNA SPECIES OF HUMAN COMPLEMENT FACTOR H REVEALS A NOVEL MEMBER OF THE SHORT CONSENSUS REPEAT FAMILY RELATED TO THE CARBOXY TERMINAL OF THE CLASSICAL 150-kDa MOLECULE

Three factor H mRNA species of 4.3 kb, 1.8 kb, and 1.4 kb are constitutively expressed in human liver. Having previously characterized full-length cDNA clones derived from the 4.3-kb and 1.8-kb factor mRNA, we report here the isolation and eucaryotic expression of full-length cDNA clones coding for the 1.4-kbm RNA species. The 1266-bp cDNA codes for a polypeptide of 330 amino acids and contains two polyadenylation signals and a short poly(A)+tailT. he protein is composed of a leader peptide followed by five short consensus repeat domains. It shows a hybrid structure with the last three domains being almost identical to the carboxy- terminal of thcel assical 1 BO-kDa factor H molecule and the two first domains representing unique short consensus repeat structures. Eucaryotic expression in COS7 cells revealed two polypeptides derived from one cDNA clone that area lso found in human serum. Differences between the cDcNloAn es within the last three domains indicate two distinct, possibly allelic sequences that, in addition, differ from the authentic 150-kDa factor H sequence. Southern blot results support the notion that the 4.3-kb factor H and the 1.4-kb factor H-related mRNA are transcribed from two separate but highly homologous genes. Factor H, a glycoprotein of 150,00

The Anemos Wind Power forecasting Platform technology - techniques and experiences

Disponible : http://www.ewec2006proceedings.info/allfiles2/966_Ewec2006fullpaper.pdfInternational audienceIn the framework of the Anemos project we developed a professional, flexible platform for operating wind power prediction models, laying the main focus on state-of-the-art IT techniques, inter-platform operability, availability and safety of operation. Currently, 7 plug-in prediction models from all over Europe are able to work on this platform

An Aggregated Stakeholder Perspective on Potential Benefits and Challenges

How can buildings be combined with agricultural production and what are the major potential benefits and challenges for the introduction of zero-acreage farming (ZFarming) in Berlin from the relevant stakeholders’ perspectives? These questions were explored through a series of interviews and stakeholder workshops held between 2011 and 2013. The aim was to identify the most suitable building-integrated farming model for the Berlin metropolitan area and to develop guidelines for the model’s successful and sustainable implementation through a stakeholder-driven approach. This paper provides an aggregated synthesis of the outcomes derived from the qualitative interviews and stakeholder workshops. As the results reveal, the stakeholders perceive potential benefits and challenges related to the issue of ZFarming in all dimensions (economic, social, environmental and political). They largely agreed on the importance of focusing on local resources, using energy- efficient production—including social and educational aspects—and developing new market structures when introducing ZFarming to the city of Berlin. The stakeholders identified urban rooftop greenhouses (RTG) as the most promising farming model for Berlin. In a joint collaboration of all stakeholders, a manual for RTG was developed within the participatory innovation process that addresses the identified problems and challenges associated with future implementation and governance of RTG in Berlin and beyond

Farming in and on urban buildings: present practice and specific novelties of Zero-Acreage Farming (ZFarming)

Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG geförderten) Allianz- bzw. Nationallizenz frei zugänglich.This publication is with permission of the rights owner freely accessible due to an Alliance licence and a national licence (funded by the DFG, German Research Foundation) respectively.Considering global trends such as climate change and resource scarcity, a major challenge of future cities will be to reduce urban footprints. Moreover, cities have to become or remain livable for their inhabitants and offer social and economic opportunities. Thus, reconnecting food production and cities offers promising potential. The diffusion of urban farming reflects a rising awareness of how food and farming can shape our cities. A growing number of urban farming projects exist in and on urban buildings, including open rooftop farms, rooftop greenhouses and indoor farming. These projects are characterized by the non-use of land or acreage for farming activities. We use the term ‘Zero-Acreage Farming’ (ZFarming) to represent these farms. The objective of this paper is to: (1) illustrate and systemize present practices of ZFarming and (2) discuss specific novelties of ZFarming in the wider context of urban agriculture. We analyzed 73 ZFarms in cities of North America, Asia, Australia and Europe using a set of criteria, and developed a typology of ZFarming, complemented by in-depth interviews with pioneers in rooftop farming in New York. The results illustrate that ZFarming generates innovative practices that may contribute to a sustainable urban agriculture. Besides growing food, it produces a range of non-food and non-market goods. It involves new opportunities for resource efficiency, new farming technologies, specific implementation processes and networks, new patterns of food supply and new urban spaces

Investigating political risk in the German energy industry

This study analyses the phenomenon of political risk in the German energy industry. Political risk can be understood as “the probability that factors caused or influenced by the (in) action or reactions of stakeholders within a political system to events outside or within the country” (Brink 2004). This study asks for determinants and characteristics of political risk, its origination, its occurrence, and its impact. The focus of this study lies in the German energy industry, where politically initiated drastic changes are the predominant challenge for utilities (Roland Berger, 2013). The industry levels investigated include strategic and risk company’s issues and are focused on the senior management and senior politicians’ insights. It looks for the identification and analysis of the linkage of political risk and their effect on utility companies in Germany of different sizes and active within different sectors. While political risk is not limited to Germany or the energy industry, there have been enormous changes in this field recently: the German government recently decided to shut down all nuclear-fuelled power plants as part of a programme called energy turnaround (Energiewende). The content of this programme will change the industry structure radically. Renewable energy is now heavily favoured with a consequent decline in nuclear energy usage. This study analyses political risk combining two approaches: an outside-in and an inside-out analysis. Two important perspectives are captured, evaluated and compared with each other. The first group of interviews focuses on senior political experts, who are strongly connected with the energy industry. This “inside” information comes from experts including members of the state and federal parliament, as well as European parliament and one former federal minister of economics. The second group of interviews therefore seeks “outside” information from industry experts, senior managers of the German energy industries, who are daily confronted with the impact of political risk. It is enriching to combine these two sides, to develop an understanding of the phenomenon of political risk in the German energy industry. The approach of having two interview series with conflicting expert opinion generates a new view of this topic. The findings illustrate these ideas, thoughts, and opinions together, which helps to explain the different sides of political risk in the German energy industry and generates approaches for the utility companies to take to mitigate political risk. The analyses of the experts’ insights generated the following results (1) identification and description of the definitional tensions of understanding political risk in the German energy industry (2) analysis of the political risks the industry is facing (3) evaluation of the potential impact of these risks on the industry and its companies (4) development of a conceptual approach for political risk management in the German energy industry. In detail, it has been derived from the analysis that there are huge differentiations in the understanding of political risk between politicians and managers. There is also no common understanding within the group of politicians. The different perception of political risk was also evident for the types of political risk that were discussed in this study. Despite the observed influence of political decisions on single enterprises in Germany in recent history, there are also differentiations in the evaluation of the impact of political risk within practice. Managers perceive it as a given fact and accept is as an element of their environment that they must interact with, whil

High risk medication regimens and medication related predictors of hospital readmission in elderly home care patients

Adverse drug events are a primary cause of hospitalization in the elderly. Nearly 70% of the $177.4 billion dollars spent on drug related morbidity and mortality in the U.S. is due to hospitalizations. Polypharmacy, inappropriate medications or medication regimen complexity have all been implicated as precursors to adverse drug events and as indicators of high risk medication regimens. Understanding the relationship between medication regimens and readmission is important when evaluating potential errors in administration, risk-benefit ratios, and readmission risk. However, due to definitional and measurement issues, the high risk medication regimen remains an elusive concept. This study characterizes medication regimens, defines high risk medication regimens, and determines if high risk medication regimens predict re-hospitalization in home healthcare clients over age 65

Follistatin-like 3 (FSTL3) mediated silencing of transforming growth factor (TGF ) signaling is essential for testicular aging and regulating testis size

Follistatin-like 3 (FSTL3) is a glycoprotein that binds and inhibits the action of TGFβ ligands such as activin. The roles played by FSTL3 and activin signaling in organ development and homeostasis are not fully understood. The authors show mice deficient in FSTL3 develop markedly enlarged testes that are also delayed in their age-related regression. These FSTL3 knockout mice exhibit increased Sertoli cell numbers, allowing for increased spermatogenesis but otherwise showing normal testicular function. The data show that FSTL3 deletion leads to increased AKT signaling and SIRT1 expression in the testis. This demonstrates a cross-talk between TGFβ ligand and AKT signaling and leads to a potential mechanism for increased cellular survival and antiaging. The findings identify crucial roles for FSTL3 in limiting testis organ size and promoting age-related testicular regression

Neutrophils Turn Plasma Proteins into Weapons against HIV-1

As a consequence of innate immune activation granulocytes and macrophages produce hypochlorite/hypochlorous acid (HOCl) via secretion of myeloperoxidase (MPO) to the outside of the cells, where HOCl immediately reacts with proteins. Most proteins that become altered by this system do not belong to the invading microorganism but to the host. While there is no doubt that the myeloperoxidase system is capable of directly inactivating HIV-1, we hypothesized that it may have an additional indirect mode of action. We show in this article that HOCl is able to chemically alter proteins and thus turn them into Idea-Ps (Idea-P = immune defence-altered protein), potent amyloid-like and SH-groups capturing antiviral weapons against HIV-1. HOCl-altered plasma proteins (Idea-PP) have the capacity to bind efficiently and with high affinity to the HIV-1 envelope protein gp120, and to its receptor CD4 as well as to the protein disulfide isomerase (PDI). Idea-PP was able to inhibit viral infection and replication in a cell culture system as shown by reduced number of infected cells and of syncytia, resulting in reduction of viral capsid protein p24 in the culture supernatant. The unmodified plasma protein fraction had no effect. HOCl-altered isolated proteins antithrombin III and human serum albumin, taken as representative examples of the whole pool of plasma proteins, were both able to exert the same activity of binding to gp120 and inhibition of viral proliferation. These data offer an opportunity to improve the understanding of the intricacies of host-pathogen interactions and allow the generation of the following hypothetical scheme: natural immune defense mechanisms generate by posttranslational modification of plasma proteins a potent virucidal weapon that immobilizes the virus as well as inhibits viral fusion and thus entry into the host cells. Furthermore simulation of this mechanism in vitro might provide an interesting new therapeutic approach against microorganisms