Fc-fusion mimetics

The Fc-fusion mimetic RpR 2 was prepared by disulfide bridging conjugation using a PEG in the place of the Fc. RpR 2 displayed higher affinity for VEGF than aflibercept caused primarily by a slower dissociation rate, which can prolong a drug at its site of action. RpRs have considerable potential for development as stable, organ specific therapeutics.

Étude des gènes de fusion MLL dans les leucémies aigues humaines

Les leucémies aigues sont la conséquence d’une prolifération clonale et maligne des cellules hématopoïétiques. Elles surviennent suite à un évènement oncogénique qui se produit dans une cellule souche hématopoïétique (CSH) ou progénitrice. Cela lui confère une certaine instabilité qui engendre l’accumulation d’autres évènements génétiques et/ou épigénétiques responsables du développement clinique de la maladie. Les leucémies MLL représentent environ 10% des leucémies aigues et aujourd’hui, plus de 70 gènes de fusion ont été caractérisés. Les sangs de cordon sont une source importante de CSH et progénitrices. La purification de ces cellules et leur transformation en cellules leucémiques à l’aide de gènes de fusion MLL nous permettent de générer des leucémies aigues humaines dans des souris immunodéficientes NSG et ainsi étudier le potentiel leucémique de différents gènes de fusion MLL. Dans un premier temps, 4 gènes de fusion MLL ont été étudiés : MLL-AF9, MLL-AF4, MLL-ENL et MLL-ELL. In vitro, nous sommes capables de transformer des CSH en cellules leucémiques capables de proliférer rapidement. Les résultats in vivo nous montrent qu’il est possible de générer des leucémies avec les oncogènes MLL-AF9 et MLL-ENL. Pour les fusions MLL-ELL et MLL-AF4, bien que quelques leucémies ont pu être obtenues, plusieurs problèmes techniques nous empêchent aujourd’hui de disposer d’un modèle adéquat permettant l’étude complète de ces oncogènes. Dans un second temps, les leucémies aigues MLL-AF9 ont été étudiées dans un modèle contrôlé où les cellules souches proviennent d’un donneur unique. Grâce à ce modèle, nous avons pu démontrer que l’oncogène MLL-AF9 est suffisant pour induire le développement de la maladie. En effet aucune nouvelle mutation n’a pu être identifiée au cours du développement de la leucémie. Parmi les leucémies myéloïdes aigues (LMA) MLL-AF9 issues de ce modèle, certains gènes non mutés, dont RET, ont été identifiés comme étant de potentiels biomarqueurs de ce sous-groupe de leucémie.

Type of strabismus and changes to fusion measures

Assessing the range of vergence provides information about the patient’s ability to maintain the binocular vision. Disparity vergence measurements should be used to quantify control of an underlying eye misalignment. In the presence of a manifest deviation the testing is performed by first compensating the angle of deviation to determine prognosis. Type of deviation: a) in an exophoria there is an increase in the fast fusional convergence while in an esophoric deviation there is an increase in reflex fusional divergence to attain binocular single vision; b) convergence fusion amplitudes have been found to correlate with control of the exodeviation; c) there is a greater BO range for esos and greater BI range for exos.

Truncation identities for the small polaron fusion hierarchy

We study a one-dimensional lattice model of interacting spinless fermions. This model is integrable for both periodic and open boundary conditions; the latter case includes the presence of Grassmann valued non-diagonal boundary fields breaking the bulk U(1) symmetry of the model. Starting from the embedding of this model into a graded Yang-Baxter algebra, an infinite hierarchy of commuting transfer matrices is constructed by means of a fusion procedure. For certain values of the coupling constant related to anisotropies of the underlying vertex model taken at roots of unity, this hierarchy is shown to truncate giving a finite set of functional equations for the spectrum of the transfer matrices. For generic coupling constants, the spectral problem is formulated in terms of a functional (or TQ-)equation which can be solved by Bethe ansatz methods for periodic and diagonal open boundary conditions. Possible approaches for the solution of the model with generic non-diagonal boundary fields are discussed.

Single-molecule fluorescence resonance energy transfer study of SNARE-mediated membrane fusion

This is a comprehensive study of protein-mediated membrane fusion through single-molecule fluorescence resonance energy transfer (smFRET). Membrane fusion is one of the important cellular processes by which two initially distinct lipid bilayers merge their hydrophobic cores, resulting in one interconnected structure. For example, exocytosis, fertilization of an egg by a sperm and communication between neurons are a few among many processes that rely on some form of fusion. Proteins called soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) play a central role in fusion processes which is also regulated by many accessory proteins, such as synaptotagmin, complexin and Munc18. By a new lipid mixing method at the single-vesicle level, we are able to accurately detect different stages of SNARE-mediated membrane fusion including docking, hemi and full fusion via FRET value of single donor/acceptor vesicle pair. Through this single-vesicle lipid mixing assay, we discovered the vesicle aggregation induced by C2AB/Ca2+, the dual function of complexin, and the fusion promotion role of Munc18/SNARE-core binding mode. While this new method provides the information regarding the extent of the ensemble lipid mixing, the fusion pore opening between two vesicular cavities and the interaction between proteins cannot be detected. In order to overcome these limitations, we then developed a single-vesicle content mixing method to reveal the key factor of pore expansion by detecting the FRET change of dual-labeled DNA probes encapsulated in vesicles. Through our single-vesicle content mixing assay, we found the fusion pore expansion role of yeast SNAREs as well as neuronal SNAREs plus synaptotagmin 1.

Information Fusion for Anomaly Detection with the Dendritic Cell Algorithm

Dendritic cells are antigen presenting cells that provide a vital link between the innate and adaptive immune system, providing the initial detection of pathogenic invaders. Research into this family of cells has revealed that they perform information fusion which directs immune responses. We have derived a Dendritic Cell Algorithm based on the functionality of these cells, by modelling the biological signals and differentiation pathways to build a control mechanism for an artificial immune system. We present algorithmic details in addition to experimental results, when the algorithm was applied to anomaly detection for the detection of port scans. The results show the Dendritic Cell Algorithm is successful at detecting port scans.

Collimation of deuterium / 3-helium fusion products for advanced spacecraft propulsion and power

Current space exploration has transpired through the use of chemical rockets, and they have served us well, but they have their limitations. Exploration of the outer solar system, Jupiter and beyond will most likely require a new generation of propulsion system. One potential technology class to provide spacecraft propulsion and power systems involve thermonuclear fusion plasma systems. In this class it is well accepted that d-He3 fusion is the most promising of the fuel candidates for spacecraft applications as the 14.7 MeV protons carry up to 80% of the total fusion power while ‘s have energies less than 4 MeV. The other minor fusion products from secondary d-d reactions consisting of 3He, n, p, and 3H also have energies less than 4 MeV. Furthermore there are two main fusion subsets namely, Magnetic Confinement Fusion devices and Inertial Electrostatic Confinement (or IEC) Fusion devices. Magnetic Confinement Fusion devices are characterized by complex geometries and prohibitive structural mass compromising spacecraft use at this stage of exploration. While generating energy from a lightweight and reliable fusion source is important, another critical issue is harnessing this energy into usable power and/or propulsion. IEC fusion is a method of fusion plasma confinement that uses a series of biased electrodes that accelerate a uniform spherical beam of ions into a hollow cathode typically comprised of a gridded structure with high transparency. The inertia of the imploding ion beam compresses the ions at the center of the cathode increasing the density to the point where fusion occurs. Since the velocity distributions of fusion particles in an IEC are essentially isotropic and carry no net momentum, a means of redirecting the velocity of the particles is necessary to efficiently extract energy and provide power or create thrust. There are classes of advanced fuel fusion reactions where direct-energy conversion based on electrostatically-biased collector plates is impossible due to potential limits, material structure limitations, and IEC geometry. Thermal conversion systems are also inefficient for this application. A method of converting the isotropic IEC into a collimated flow of fusion products solves these issues and allows direct energy conversion. An efficient traveling wave direct energy converter has been proposed and studied by Momota , Shu and further studied by evaluated with numerical simulations by Ishikawa and others. One of the conventional methods of collimating charged particles is to surround the particle source with an applied magnetic channel. Charged particles are trapped and move along the lines of flux. By introducing expanding lines of force gradually along the magnetic channel, the velocity component perpendicular to the lines of force is transferred to the parallel one. However, efficient operation of the IEC requires a null magnetic field at the core of the device. In order to achieve this, Momota and Miley have proposed a pair of magnetic coils anti-parallel to the magnetic channel creating a null hexapole magnetic field region necessary for the IEC fusion core. Numerically, collimation of 300 eV electrons without a stabilization coil was demonstrated to approach 95% at a profile corresponding to Vsolenoid = 20.0V, Ifloating = 2.78A, Isolenoid = 4.05A while collimation of electrons with stabilization coil present was demonstrated to reach 69% at a profile corresponding to Vsolenoid = 7.0V, Istab = 1.1A, Ifloating = 1.1A, Isolenoid = 1.45A. Experimentally, collimation of electrons with stabilization coil present was demonstrated experimentally to be 35% at 100 eV and reach a peak of 39.6% at 50eV with a profile corresponding to Vsolenoid = 7.0V, Istab = 1.1A, Ifloating = 1.1A, Isolenoid = 1.45A and collimation of 300 eV electrons without a stabilization coil was demonstrated to approach 49% at a profile corresponding to Vsolenoid = 20.0V, Ifloating = 2.78A, Isolenoid = 4.05A 6.4% of the 300eV electrons’ initial velocity is directed to the collector plates. The remaining electrons are trapped by the collimator’s magnetic field. These particles oscillate around the null field region several hundred times and eventually escape to the collector plates. At a solenoid voltage profile of 7 Volts, 100 eV electrons are collimated with wall and perpendicular component losses of 31%. Increasing the electron energy beyond 100 eV increases the wall losses by 25% at 300 eV. Ultimately it was determined that a field strength deriving from 9.5 MAT/m would be required to collimate 14.7 MeV fusion protons from d-3He fueled IEC fusion core. The concept of the proton collimator has been proven to be effective to transform an isotropic source into a collimated flow of particles ripe for direct energy conversion.

Représentations et fusion des algèbres de Temperley-Lieb originale et diluée

Les algèbres de Temperley-Lieb originales, aussi dites régulières, apparaissent dans de nombreux modèles statistiques sur réseau en deux dimensions: les modèles d'Ising, de Potts, des dimères, celui de Fortuin-Kasteleyn, etc. L'espace d'Hilbert de l'hamiltonien quantique correspondant à chacun de ces modèles est un module pour cette algèbre et la théorie de ses représentations peut être utilisée afin de faciliter la décomposition de l'espace en blocs; la diagonalisation de l'hamiltonien s'en trouve alors grandement simplifiée. L'algèbre de Temperley-Lieb diluée joue un rôle similaire pour des modèles statistiques dilués, par exemple un modèle sur réseau où certains sites peuvent être vides; ses représentations peuvent alors être utilisées pour simplifier l'analyse du modèle comme pour le cas original. Or ceci requiert une connaissance des modules de cette algèbre et de leur structure; un premier article donne une liste complète des modules projectifs indécomposables de l'algèbre diluée et un second les utilise afin de construire une liste complète de tous les modules indécomposables des algèbres originale et diluée. La structure des modules est décrite en termes de facteurs de composition et par leurs groupes d'homomorphismes. Le produit de fusion sur l'algèbre de Temperley-Lieb originale permet de «multiplier» ensemble deux modules sur cette algèbre pour en obtenir un autre. Il a été montré que ce produit pouvait servir dans la diagonalisation d'hamiltoniens et, selon certaines conjectures, il pourrait également être utilisé pour étudier le comportement de modèles sur réseaux dans la limite continue. Un troisième article construit une généralisation du produit de fusion pour les algèbres diluées, puis présente une méthode pour le calculer. Le produit de fusion est alors calculé pour les classes de modules indécomposables les plus communes pour les deux familles, originale et diluée, ce qui vient ajouter à la liste incomplète des produits de fusion déjà calculés par d'autres chercheurs pour la famille originale. Finalement, il s'avère que les algèbres de Temperley-Lieb peuvent être associées à une catégorie monoïdale tressée, dont la structure est compatible avec le produit de fusion décrit ci-dessus. Le quatrième article calcule explicitement ce tressage, d'abord sur la catégorie des algèbres, puis sur la catégorie des modules sur ces algèbres. Il montre également comment ce tressage permet d'obtenir des solutions aux équations de Yang-Baxter, qui peuvent alors être utilisées afin de construire des modèles intégrables sur réseaux.

Institutions de microfinance et prêteurs informels de l’agriculture familiale en Côte d’ivoire : de la cohabitation à la fusion

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Information fusion in the immune system

Biologically-inspired methods such as evolutionary algorithms and neural networks are proving useful in the field of information fusion. Artificial immune systems (AISs) are a biologically-inspired approach which take inspiration from the biological immune system. Interestingly, recent research has shown how AISs which use multi-level information sources as input data can be used to build effective algorithms for realtime computer intrusion detection. This research is based on biological information fusion mechanisms used by the human immune system and as such might be of interest to the information fusion community. The aim of this paper is to present a summary of some of the biological information fusion mechanisms seen in the human immune system, and of how these mechanisms have been implemented as AISs.

STORM - a novel information fusion and cluster interpretation technique

Analysis of data without labels is commonly subject to scrutiny by unsupervised machine learning techniques. Such techniques provide more meaningful representations, useful for better understanding of a problem at hand, than by looking only at the data itself. Although abundant expert knowledge exists in many areas where unlabelled data is examined, such knowledge is rarely incorporated into automatic analysis. Incorporation of expert knowledge is frequently a matter of combining multiple data sources from disparate hypothetical spaces. In cases where such spaces belong to different data types, this task becomes even more challenging. In this paper we present a novel immune-inspired method that enables the fusion of such disparate types of data for a specific set of problems. We show that our method provides a better visual understanding of one hypothetical space with the help of data from another hypothetical space. We believe that our model has implications for the field of exploratory data analysis and knowledge discovery.

Sulphated polysaccharides from Ulva clathrata and Cladosiphon okamuranus seaweeds both inhibit viral attachment/entry and cell-cell fusion, in NDV infection

Sulphated polysaccharides (SP) extracted from seaweeds have antiviral properties and are much less cytotoxic than conventional drugs, but little is known about their mode of action. Combination antiviral chemotherapy may offer advantages over single agent therapy, increasing efficiency, potency and delaying the emergence of resistant virus. The paramyxoviridae family includes pathogens causing morbidity and mortality worldwide in humans and animals, such as the Newcastle Disease Virus (NDV) in poultry. This study aims at determining the antiviral activity and mechanism of action in vitro of an ulvan (SP from the green seaweed Ulva clathrata), and of its mixture with a fucoidan (SP from Cladosiphon okamuranus), against La Sota NDV strain. The ulvan antiviral activity was tested using syncytia formation, exhibiting an IC50 of 0.1 μg/mL; ulvan had a better anti cell-cell spread effect than that previously shown for fucoidan, and inhibited cell-cell fusion via a direct effect on the F0 protein, but did not show any virucidal effect. The mixture of ulvan and fucoidan showed a greater anti-spread effect than SPs alone, but ulvan antagonizes the effect of fucoidan on the viral attachment/entry. Both SPs may be promising antivirals against paramyxovirus infection but their mixture has no clear synergistic advantage