Major hazard prevention is a main challenge given that it is specifically based on information communicated to the public. In France, preventive information is notably provided by way of local ...regulatory documents. Unfortunately, the law requires only few specifications concerning their content; therefore one can question the impact on the general population relative to the way the document is concretely created. Ergo, the purpose of our work is to propose an analytical methodology to evaluate preventive risk communication document effectiveness. The methodology is based on dependability approaches and is applied in this paper to the Document d'Information Communal sur les Risques Majeurs (DICRIM; in English, Municipal Information Document on Major Risks). DICRIM has to be made by mayors and addressed to the public to provide information on major hazards affecting their municipalities. An analysis of law compliance of the document is carried out thanks to the identification of regulatory detection elements. These are applied to a database of 30 DICRIMs. This analysis leads to a discussion on points such as usefulness of the missing elements. External and internal function analysis permits the identification of the form and content requirements and service and technical functions of the document and its components (here its sections). Their results are used to carry out an FMEA (failure modes and effects analysis), which allows us to define the failure and to identify detection elements. This permits the evaluation of the effectiveness of form and content of each components of the document. The outputs are validated by experts from the different fields investigated. Those results are obtained to build, in future works, a decision support model for the municipality (or specialised consulting firms) in charge of drawing up documents.
Knowledge about action undergone by an obstacle impacted by an avalanche is still insufficient to allow civil engineers to design really efficient and resistant structures. The main difficulty is to ...take into account the mutual interactions that occur between the structure and the flow and the influence of the obstacle on the avalanche action itself. An original back-analysis principle is proposed to obtain information on avalanche action from real destructive event and to ensure that the result is effectively what is undergone by the structure and not only what could be generated by the phenomenon. In that way, the destruction of two deflective walls in Taconnaz site by the 11th of February 1999 exceptional avalanche is studied with several parts: firstly, a large site investigation program is conducted to gather observations including material specimen's tests and to exhibit two collapse scenarios. Then, laboratory experiments are performed to confirm failure mechanisms. Finally, numerical simulations used a rigorous three-dimensional finite elements model and a realistic representation of the concrete behaviour to evaluate the effective resistance of the structures under different conditions, including quasi-static, cyclic and dynamic influences.
A facilitated diffusion for glycerol is present in human erythrocytes. Glycerol transporters identified to date belong to
the M ajor I ntrinsic P rotein (MIP) family of integral membrane proteins, ...and one of them, aquaporin-3 (AQP3), has been characterized in mammals.
Using an antibody raised against a peptide corresponding to the rat AQP3 carboxyl terminus, we examined the presence of AQP3
in normal and Colton-null (aquaporin-1 (AQP1)-deficient) human erythrocytes. Three immunoreactive bands were detected on immunoblots
of both normal and Colton-null red cells, very similar to the bands revealed in rat kidney, a material in which AQP3 has been
extensively studied. By immunofluorescence, anti-AQP3 antibodies stained the plasma membranes of both normal and Colton-null
erythrocytes. Glycerol transport was measured on intact erythrocytes by stopped-flow light scattering and on one-step pink
ghosts by a rapid filtration technique. Glycerol permeability values, similar in both cell types, suggest that AQP1 does not
represent the major path for glycerol movement across red blood cell membranes. Furthermore, pharmacological studies showed
that Colton-null red cells remain sensitive to water and glycerol flux inhibitors, supporting the idea that another proteinaceous
path, probably AQP3, mediates most of the glycerol movements across red cell membranes and represents part of the residual
water transport activity found in AQP1-deficient red cells.
The search for improvement of protective techniques against natural phenomena, such as snow avalanches, continues to use classic methods for calculating flexible structures. This paper proposes a new ...method for designing avalanche protection nets based on the mechanical balance of cable structures, inspired by the mechanics of solids. This has led to the development of computational software so that avalanche nets can be easily designed. Numerical and experimental results have been compared, yielding elements to validate this new approach. Finally, several future research perspectives are discussed that will add to the modeling of interactions between flexible structures and complex geomaterials, such as a snow mantel.
C1q, the binding subunit of the C1 complex of complement, is an archetypal pattern recognition molecule known for its striking ability to recognize a wide variety of targets, ranging from pathogenic ...non self to altered self. DNA is one of the C1q ligands, but the precise region of C1q and the DNA motifs that support interaction have not been characterized yet. Here, we report for the first time that the peripheral globular region of the C1q molecule displays a lectin-like activity, which contributes to DNA binding through interaction with its deoxy-
d-ribose moiety and may participate in apoptotic cell recognition.
Granulomatosis with polyangiitis (GPA) is an autoimmune vasculitis associated with anti-neutrophil-cytoplasmic antibodies (ANCA) against proteinase 3 leading to kidney damage. Neutrophils from those ...patients have increased expression of membrane proteinase 3 during apoptosis. Here we examined whether neutrophils from patients with GPA have dysregulated protein expressions associated with apoptosis. A global proteomic analysis was performed comparing neutrophils from patients with GPA, with healthy individuals under basal conditions and during apoptosis. At disease onset, the cytosolic proteome of neutrophils of patients with GPA before treatment was significantly different from healthy controls, and this dysregulation was more pronounced following ex vivo apoptosis. Proteins involved in cell death/survival were altered in neutrophils of patients with GPA. Several proteins identified were PR3-binding partners involved in the clearance of apoptotic cells, namely calreticulin, annexin-A1 and phospholipid scramblase 1. These proteins form a platform at the membrane of apoptotic neutrophils in patients with GPA but not healthy individuals and this was associated with the clinical presentation of GPA. Thus, our study shows that neutrophils from patients with GPA have an intrinsic dysregulation in proteins involved in apoptotic cell clearance, which could contribute to the unabated inflammation and autoimmunity in GPA. Hence, harnessing these dysregulated pathways could lead to novel biomarkers and targeted therapeutic opportunities to treat kidney disease.
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Direct interaction between CD91 and C1q Duus, Karen; Hansen, Erik W; Tacnet, Pascale ...
The FEBS journal,
September 2010, Letnik:
277, Številka:
17
Journal Article
Recenzirano
Odprti dostop
C1q-mediated removal of immune complexes and apoptotic cells plays an important role in tissue homeostasis and the prevention of autoimmune conditions. It has been suggested that C1q mediates ...phagocytosis of apoptotic cells through a receptor complex assembled from CD91 (α-2- macroglobulin receptor, or low-density lipoprotein receptor-related protein) and calreticulin, with CD91 being the transmembrane part and calreticulin acting as the C1q-binding molecule. In the present study, we observe that C1q binds cells from a CD91 expressing monocytic cell line as well as monocytes from human blood. C1q binding to monocytes was shown to be correlated with CD91 expression and could be inhibited by the CD91 chaperone, receptor-associated protein. We also report data showing a direct interaction between CD91 and C1q. The interaction was investigated using various protein interaction assays. A direct interaction between purified C1q and CD91 was observed both by ELISA and a surface plasmon resonance assay, with either C1q or CD91 immobilized. The interaction showed characteristics of specificity because it was time-dependent, saturable and could be inhibited by known ligands of both CD91 and C1q. The results obtained show for the first time that CD91 recognizes C1q directly. On the basis of these findings, we propose that CD91 is a receptor for C1q and that this multifunctional scavenger receptor uses a subset of its ligand-binding sites for clearance of C1q and C1q bound material.
This paper presents a new approach for combining sources of evidences with different importances and reliabilities. Usually, the combination of sources of evidences with different reliabilities is ...done by the classical Shafer's discounting approach. Therefore, to consider unequal importances of sources, if any, a similar reliability discounting process is generally used, making no difference between the notion of importance and reliability. In fact, in multicriteria decision context, these notions should be clearly distinguished. This paper shows how this can be done and we provide simple examples to show the differences between both solutions for managing importances and reliabilities of sources. We also discuss the possibility for mixing them in a global fusion process.
As soluble recognition molecules of innate immunity, C1q and MBL are able to bind directly to various viruses, including retroviruses and influenza viruses. Interaction of C1q with retroviruses and ...certain infected cells was shown to involve the globular region of C1q and viral envelope glycoproteins, such as p15E of MuLV, gp41 and gp120 of HIV-1, gp21 of HTLV-1. C1q binding was found to trigger antibody-independent activation of the classical pathway of complement, but did not lead to virus destruction and had even an adverse effect on infection in humans, because of subversion of the complement system by the virus. Binding of MBL or of the pulmonary collectin SP-D to influenza A virus was shown to involve the carbohydrate recognition domain of the molecule and high-mannose oligosaccharides of the viral proteins haemagglutinin and neuraminidase. These interactions lead to virus inactivation, are independent of complement activation and are influenced by the oligomerization state of the collectin.
The temperature-sensitive
Saccharomyces cerevisiae mutant strain NY17, deficient in the secretory pathway (
sec6-4 mutation), is used for the heterologous expression of the human CHIP28 water ...channel. After a heat-shock, the protein is present in partially purified post-golgi secretory vesicles. Immunodetection and water transport studies, directly made on the vesicles, showed that CHIP28 is highly expressed and active in the yeast membranes.
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