407 research outputs found
Polysaccharide antigen-glycolipid conjugate vaccines
The present invention relates to the field of synthesizing and biologically evaluating of a novel class of carbohydratebased vaccines. The new vaccines consist of a multi- modular structure which allows applying the vaccine to a whole variety of pathogenes. This method allows preparing vaccines against all pathogens expressing immunogenic carbohydrate antigens. As conjugation of antigenic carbohydrates to proteins is not required the conjugate vaccine is particularly heat stable. No refrigeration is required, a major drawback of protein-based vaccines
Presentation of the Same Glycolipid by Different CD1 Molecules
Five CD1 molecules are expressed in humans and it is unclear whether they have specialized or redundant functions. We found that sulfatide is a promiscuous CD1-binding ligand and have isolated T cell clones that are specific for sulfatide and restricted by distinct CD1 molecules. These clones have been used to compare the capacity of different CD1 to present the same glycolipid, to induce effector functions, and to form persistent immunogenic complexes. CD1a, CD1b, and CD1c molecules similarly load sulfatide on the cell surface without processing, and prime Th1 and Th2 responses. Stimulation by sulfatide-loaded CD1a persists much longer than that by CD1b and CD1c in living cells. Use of recombinant soluble CD1a confirmed the prolonged capacity to stimulate T cells. Moreover, other glycosphingolipids bind to all CD1, which suggests the presence of additional promiscuous ligands. Thus, group I CD1 molecules present an overlapping set of self-glycolipids, even though they are quite divergent from an evolutionary point of view
Dynamics of a tunneling magnetic impurity: Kondo effect induced incoherence
We study how the formation of the Kondo compensation cloud influences the
dynamical properties of a magnetic impurity that tunnels between two positions
in a metal. The Kondo effect dynamically generates a strong tunneling
impurity-conduction electron coupling, changes the temperature dependence of
the tunneling rate, and may ultimately result in the destruction of the
coherent motion of the particle at zero temperature. We find an interesting
two-channel Kondo fixed point as well for a vanishing overlap between the
electronic states that screen the magnetic impurity. We propose a number of
systems where the predicted features could be observed.Comment: 4 pages, 3 figures, ReVTe
Instability of the marginal commutative model of tunneling centers interacting with metallic environment: Role of the electron-hole symmetry breaking
The role of the electron-hole symmetry breaking is investigated for a
symmetrical commutative two-level system in a metal using the multiplicative
renormalization group in a straightforward way. The role of the symmetries of
the model and the path integral technique are also discussed in detail. It is
shown that the electron-hole symmetry breaking may make the model
non-commutative and generate the assisted tunneling process which is, however,
too small itself to drive the system into the vicinity of the two-channel Kondo
fixed point. While these results are in qualitative agreement with those of
Moustakas and Fisher (Phys. Rev. B 51, 6908 (1995), ibid 53, 4300 (1996)) the
scaling equations turn out to be essentially different. We show that the main
reason for this difference is that the procedure for the elimination of the
high energy degrees of freedom used by Moustakas and Fisher leaves only the
free energy invariant, however, the couplings generated are not connected to
the dynamical properties in a straightforward way and should be interpreted
with care. These latter results might have important consequences in other
cases where the path integral technique is used to produce the scaling
equations and calculate physical quantities.Comment: latex, figures in ps file adde
Embryonal tumors with abundant neuropil and true Rosettes: A distinctive CNS primitive neuroectodermal tumor
Embryonal neoplasms of the central nervous system (CNS) generally arise in the early years of life and behave in a clinically aggressive manner, but vary somewhat in their microscopic appearance. Several groups have reported examples of an embryonal tumor with combined histologic features of ependymoblastoma and neuroblastoma, a lesion referred to as "embryonal tumor with abundant neuropil and true rosettes" (ETANTR). Herein, we present 22 new cases, and additional clinical follow-up on our 7 initially reported cases, to better define the histologic features and clinical behavior of this distinctive neoplasm. It affects infants and arises most often in cerebral cortex, the cerebellum and brainstem being less frequent sites. Unlike other embryonal tumors of the CNS, girls are more commonly affected than boys. On neuroimaging, the tumors appear as large, demarcated, solid masses featuring patchy or no contrast enhancement. Five of our cases (18%) were at least partly cystic. Distinctive microscopic features include a prominent background of mature neuropil punctuated by true rosettes formed of pseudo-stratified embryonal cells circumferentially disposed about a central lumen (true rosettes). Of the 25 cases with available follow-up, 19 patients have died, their median survival being 9 months. Performed on 2 cases, cytogenetic analysis revealed extra copies of chromosome 2 in both. We believe that the ETANTR represents a histologically distinctive form of CNS embryonal tumor. ©2009 by Lippincott Williams & Wilkins
Modelling and Simulation of Asynchronous Real-Time Systems using Timed Rebeca
In this paper we propose an extension of the Rebeca language that can be used
to model distributed and asynchronous systems with timing constraints. We
provide the formal semantics of the language using Structural Operational
Semantics, and show its expressiveness by means of examples. We developed a
tool for automated translation from timed Rebeca to the Erlang language, which
provides a first implementation of timed Rebeca. We can use the tool to set the
parameters of timed Rebeca models, which represent the environment and
component variables, and use McErlang to run multiple simulations for different
settings. Timed Rebeca restricts the modeller to a pure asynchronous
actor-based paradigm, where the structure of the model represents the service
oriented architecture, while the computational model matches the network
infrastructure. Simulation is shown to be an effective analysis support,
specially where model checking faces almost immediate state explosion in an
asynchronous setting.Comment: In Proceedings FOCLASA 2011, arXiv:1107.584
The Role of Innate Immunity in Autoimmunity
During the 2004 International Congress of Immunology in Montreal, a panel of experts gathered for an “Ideashop” discussion on the potential role of innate immunity in autoimmunity and the ways in which this might be targeted in future therapies
Clinical and transcriptional response to the long‐acting interleukin‐1 blocker canakinumab in Blau syndrome–related uveitis
Objective. To report on the clinical response to canakinumab in a patient with sporadic nucleotide-binding oligomerization domain-containing protein 2 (NOD-2)-associated pediatric granulomatous arthritis (Blau syndrome) and severe resistant panuveitis, and to describe gene expression profile changes throughout such treatment. Methods. A 4-year-old boy was diagnosed as having Blau syndrome on the basis of typical clinical features, histologic evidence of noncaseating granulomas, and a NOD2 mutation. Ocular involvement was initially controlled by topical and oral corticosteroids, but over the years visual impairment and complications, such as macular edema and retinal detachment, progressed. Ocular disease remained persistently active despite treatment with multiple different immuno-suppressants; therefore, canakinumab treatment was started. Before and during the first 6 months of treatment, the gene expression profile was determined each month. Results. Canakinumab treatment was well tolerated and led to rapid quiescence of uveitis, which had been continuously active before this treatment. Gene expression profiling analysis of the patient's blood prior to initiation of interleukin-1 (IL-1) blockade revealed differential expression of 1,993 transcripts when compared to healthy controls, and among the up-regulated transcripts, pathway analysis showed that the predominant network consisted of innate immunity-related transcripts. The transcriptional signature of the patient overlapped with the transcriptional signature of patients with systemic-onset juvenile idiopathic arthritis, and canakinumab treatment led to the normalization of most of these transcriptional changes. Conclusion. The pathogenesis of Blau syndrome may be mediated by IL-1, and canakinumab may be useful when this disorder is unresponsive to more conventional treatments
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