1,721,060 research outputs found
Characterization of invariant NKT cell phenotype and function in Wiskott-Aldrich Syndrome (WAS)
Full text linkWASp è una proteina che regola il rimodellamento dell’actina del citoscheletro nelle cellule ematopoietiche. Mutazioni nel gene che codifica per WASp (WAS) causano la Sindrome di Wiskott-Aldrich (WAS). Sebbene WASp sia coinvolto in svariate funzioni delle cellule del sistema immunitario, il suo ruolo nei linfociti invarianti NKT (iNKT) non è mai stato investigato. Difetti delle cellule iNKT potrebbero infatti contribuire allo sviluppo di alcune caratteristiche dei pazienti WAS quali le infezioni ricorrenti e l’ alta incidenza tumorale. Infatti il nostro studio ha rivelato una profonda riduzione numerica dei linfociti iNKT periferici nei pazienti WAS, direttamente correlata con la severità del fenotipo clinico dei pazienti. Per definire ulteriormente il fenotipo delle cellule iNKT prive di WASp, abbiamo esteso l’analisi ai topi was-/-. Le cellule iNKT sono significativamente ridotte anche nel timo e negli organi linfoidi periferici dei topi was-/- rispetto ai controlli wt. Inoltre l’analisi dello sviluppo delle cellule was-/- iNKT cell ha messo in luce un completo blocco maturativo allo stadio intermedio CD44+NK1.1-. In particolare, la generazione di chimere di midollo osseo, ha dimostrato un difetto maturativo intrinseco delle cellule was-/- iNKT. L’assenza di WASp non altera la stimolazione indotta dall’IL-15, che è importante nello sviluppo delle cellule iNKT. Contrariamente, WASp è coinvolto nel controllo della proliferazione omeostatica di questa tipologia cellulare. Le cellule iNKT prive di WASp presentano anche un difetto funzionale, come messo in evidenza dalla ridotta secrezione di IL-4 e IFN-γ dopo la loro attivazione in vivo. In aggiunta, saggi funzionali condotti in vitro, suggeriscono che il difetto funzionale delle cellule iNKT prive di WASp sia mediato dal TCR e che la ridotta produzione di IL-4 sia causata da un difetto funzionale intrinseco alle cellule iNKT, mentre la minor produzione di IFN-γ sembra derivare da un’interazione non efficiente tra le cellule was-/- iNKT cells e le cellule dendritiche was-/-. Nel loro insieme questi risultati dimostrano il ruolo rilevante di WASp nell’integrare segnali critici per lo sviluppo e la funzione delle cellule iNKT, e suggeriscono che i difetti di questa popolazione linfocitaria possano contribuire alla patologia della Sindrome di Wiskott-Aldrich.WAS protein (WASp) is a key regulator of actin cytoskeleton in hematopoietic cells. Mutations of WAS gene cause the Wiskott-Aldrich Syndrome (WAS). Although WASp is involved in various immune cell functions, its role in invariant NKT cells (iNKT) has never been investigated. Defects of iNKT cells could contribute to the pathogenesis of several WAS features, such as recurrent infections and high tumor incidence. Indeed, we found a profound reduction of circulating iNKT cells in WAS patients, directly correlating with the severity of clinical phenotype. To better characterize iNKT cell defect in the absence of WASp, we analyzed was-/- mice. iNKT cell number is significantly reduced in thymus and periphery of was-/- mice as compared to wt controls. Moreover analysis of was-/- iNKT cell maturation reveals a complete arrest at the CD44+NK1.1- intermediate stage. Notably, generation of BM chimeras demonstrated a was-/- iNKT cell autonomous developmental defect. The lack of WASp does not affect IL-15 signaling, which is important in iNKT cell development. Conversely WASp is required for the control of homeostatic proliferation. was-/- iNKT cells are also functionally impaired, as suggested by the lower expansion and reduced secretion of IL-4 and IFN-γ upon in vivo activation. Furthermore, in vitro assays suggest that the functional defect of WASp null iNKT cells is TCR-mediated and indicated that the defective IL-4 production is due to a was-/- iNKT cell autonomous defect, whereas the lower IFN-γ production is caused by an inefficient crosstalk between was-/- iNKT cells and was-/- DC. Altogether, these results demonstrate the relevance of WASp in integrating signals critical for development and functional differentiation of iNKT cells, and suggest that defects in these cells may play a role in WAS pathology
Alterazioni strutturali del circolo ombelico placentare: un caso clinico di mancato IUGR
No full textA text classification framework based on optimized error correcting output code
No full textIn recent years, there has been increasing interest in using text classifiers for retrieving and filtering infomation from web sources. As the numbers of categories in this kind of software applications can be high, Error correcting Output Coding (ECOC) can be a valid approach to perform multi-class classification. This paper explores the use of ECOC for learning text classifiers using two kinds of dichotomizers and compares them to each corresponding monolithic classifier. We propose a simulated annealing approach to calculate the coding matrix using an energy function similar to the electrostatic potential energy of a system of charges, which allows to maximize the average distance between codewords |with low variance. In addition, we use a new criterion for selecting features, a feature (in this specific context) being any term that may occur in a document. This criterion defines a measure of discriminant capability and allows to order terms according to it. Three different measures have been experimented to perform feature ranking/selection, in a comparative setting. Experimental results show that reducing the set of features used to train classifiers does not affect classification performance. Notably, feature selection is not a preprocessing activity valid for all dichotomizers. In fact, features are selected for each dichotomizer that occurs in the matrix coding, typically giving rise to a different subset of features depending on the dichotomizers at hand
Efficient implementation of the Yule-Simon stochastic process for modeling internet and software development activities
No full textWe develop three different algorithms for implementing the Preferential Attachment mechanism, with regards to the Yule process, able to describe how statistical power-law distributions, for various properties of OO software systems and of the internet, are generated. Since modern software systems have reached a huge dimension, counting tens, or hundreds of thousand, of units or modules, the efficiency of algorithms for their simulation is a critical issue. We discuss their efficiency for different parameters value, their scaling with system size, and analyze in which cases one is preferable with respect to the others
Three efficient algorithms for implementing the preferential attachment mechanism in Yule-Simon Stochastic Process
No full textWe describe how different optimized algorithms may be effective in implementing the preferential attachment mechanism in different cases. We analyze performances with respect to different values of some parameters related to the Yule process associated to the preferential attachment. We examine how performance scales with system size and provide extensive simulations to support our theoretical findings
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
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