112,973 research outputs found
Flows of singular vector fields and applications to fluid and kinetic equations
No full textSeveral physical phenomena arising in fluid dynamics and kinetic equations can be modeled by nonlinear transport PDE. Such quantities are the vorticity of a fluid, or the density of a collection of particles advected by a velocity field which is highly irregular. The theory of characteristics provides a link between this PDE and the ODE dX/dt=b(t,X(t,x)), where b is the velocity field. When b has Sobolev or BV regularity and bounded divergence, the theory of DiPerna-Lions and Ambrosio gives a good notion of solution to the ordinary differential equation using the concept of regular Lagrangian flow. Extending the results of Crippa-DeLellis, and more recently Bouchut-Crippa, we study Lagrangian flows associated to velocity fields with anisotropic regularity: those with gradient given by the singular integral of an L^1 function in some directions, and the singular integral of a measure in others. We exploit an anisotropic version of the previous arguments and estimate the difference quotients in this context, thereby gaining quantitative estimates in terms of the given regularity bounds. One then recovers well-posedness for the ordinary differential equation. This answers positively the question of existence of Lagrangian solutions to the Vlasov Poisson and Euler equations with L^1 data
CELL BLOCKS OF CANINE AND FELINE EFFUSION
No full textABSTRACT
Valentina Crippa
Cell Blocks from canine and feline effusions
Objective: To evaluate the sensitivity and specificity of a panel of markers in distinguishing mesothelial cells from metastatic adenocarcinoma cells in Cell blocks from canine and feline effusion.
Methods: This study included 28 effusion specimens from dogs and cats with a cytological diagnosis of reactive effusion or malignancy of non-hematopoietic origin. Cell Blocks were stained with a standard panel of Vimentin, panCK (MNF116), CK 5/6 and HBME-1 as mesothelial cell markers; Desmin as marker of benign mesothelial cells; Claudin 4 as epithelial marker and CK7/CK20 as a marker of metastasis. Malignancy was confirmed by histologic evaluation; non-malignant conditions were confirmed by histopathology or follow up. Sensitivities, specificities, predictive values and accuracy were calculated.
Results: CK5/6 demonstrated a high specificity (100%) for mesothelium. For the detection of canine and feline mesothelial cells the coexpression of panCK and VIM displayed the best sensibility (94,1%) while HBME-1 was the antibody that presented highest accuracy. Claudin 4 demonstrated a very low sensibility versus canine and feline epithelial cells.
Conclusion: The most specific marker, with for the identification of mesothelial cells in canine and effusion, is the Vim/CK coexpression, being CK5/6 the most specific and HBME-1 the marker with the highest overall accuracy. Desmin is a useful marker in discriminating between benign and malignant mesothelial cells. The coordinate expression of CK7/CK20+ has not proved to be useful on the identification of metastatic cells on effusion. The study of Claudin 4 necessitate to be deepened in veterinary medicine. In conclusion, the combination of both cytology and immunohistochemistry studies can greatly enhance the diagnostic accuracy, sensitivity and specificity in malignant effusions
Continuity equations and ODE flows with non-smooth velocity
No full textIn this paper we review many aspects of the well-posedness theory for the Cauchy problem for the continuity and transport equations and for the ordinary differential equation (ODE). In this framework, we deal with velocity fields that are not smooth, but enjoy suitable 'weak differentiability' assumptions. We first explore the connection between the partial differential equation (PDE) and the ODE in a very general non-smooth setting. Then we address the renormalization property for the PDE and prove that such a property holds for Sobolev velocity fields and for bounded variation velocity fields. Finally, we present an approach to the ODE theory based on quantitative estimates
Strong continuity for the 2D Euler equations
No full textWe prove two results of strong continuity with respect to the initial datum for bounded solutions to the Euler equations in vorticity form. The first result provides sequential continuity and holds for a general bounded solution. The second result provides uniform continuity and is restricted to Hölder continuous solutions
Clearance mechanisms of aggregated TDP-43 responsible for ALS/FTD diseases
No full textIncreasing biochemical and genetic evidence have suggested that Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Dementia (FTD) are two related neurodegenerative diseases, with a continuous clinical spectrum. Even if the neuronal population affected may differ between ALS and FTD, a common feature is the mislocalization and aggregation of the TAR DNA binding protein 43 (TDP-43), in affected cells. TDP-43 aggregates contain C-terminal TDP-43 fragments of 35 kDa (TDP-35) and 25 kDa (TDP-25), that are highly aggregation-prone, and are thought to be neurotoxic. We have investigated the role of protein quality control (PQC) system and extracellular vesicles in the clearance of TDP-43 and its C-terminal fragments. We have demonstrated that all TDP-43 species are cleared by proteasome, but TDP-25 impairs autophagy. We found that the routing of TDP fragments to proteasome or to autophagy decreased the accumulation of both TDP43 fragments, possibly reducing their toxicity. Moreover, we observed that all TDP-43 species are secreted in EVs, mainly in MVs
The role of the HSPB8-BAG3 complex in age-related protein misfolding diseases
No full textBackground and Purpose - The aggregation of misfolded, mutated proteins (SOD1, TDP-43) is a pathological hallmark of the familial forms of Amyotrophic Lateral Sclerosis (ALS). Cells have evolved an elaborate protein quality control system mediated by molecular chaperones, in order to facilitate folding/refolding of these misfolded species that can exert neurotoxicity. When folding is unsuccessful, chaperones can also target the misfolded proteins for degradation, thereby preventing protein aggregation. Intracellular degradation is primarily mediated by two proteolytic systems: the ubiquitin proteasome system and autophagy [1], and a proper balance and cross-talk between them is required for normal protein homeostasis, while their alteration may contribute to ageing and disease [2,3].
We already published that overexpression of the small heat shock protein HSPB8 (and its partner Bag3) in motoneuron cells (NSC34) prevents aggregation of mutated SOD1 and TDP-43, by either directly targeting them to the autophagic vacuoles for degradation and/or restoring/boosting the autophagy flux [4,5]. Moreover our recent data indicate that BAG3 upregulation, following proteasome inhibition, significantly contributes to the compensatory activation of autophagy and to the re-routing of (poly)ubiquitinated proteins to autophagy for degradation. Motoneurons are particularly sensitive to misfolded protein toxicity, but also other cell types could be affected. As an example, muscle-restricted expression of the mutSOD1, results in muscle atrophy associated with motoneuron death.
Methods and Results - We compared the potential mutSOD1 toxicity in motoneuron (NSC34) and muscle (C2C12) cells, and found that muscle ALS models possess much higher proteasome activity and autophagic power than motoneuron ALS models, which allow to better cope with misfolded protein aggregation [6]. The same results were also obtained with mutTDP43. These findings were further confirmed analyzing the expression of the LC3 and p62 genes (two well known autophagic markers) as well as of BAG3 and HSPB8 genes, which after proteasome inhibition are all higher activated in muscle cells than motoneuron cells. Finally we also found that the knock-down of HSPB8 increases the aggregation of both wt and mutTDP43 in C2C12, but only of mutTDP43 in NSC34, suggesting that HSPB8 plays a primary role in TDP43 turn-over especially in muscle cells.
Conclusions - These data together with the observation that HSPB8 and BAG3 are upregulated in muscles of ALS transgenic mice only at symptomatic stage and that HSPB8 is upregulated in surviving motor neurons in transgenic ALS mice during disease progression, strongly suggest that the boosting of this complex may serve to clear aggregates in chronic neurodegenerative diseases.
References
[1] Rubinsztein DC. 2006. The roles of intracellular protein-degradation pathways in neurodegeneration. Nature 443:780-786.
[2] Gamerdinger M, Hajieva P, Kaya AM, Wolfrum U, Hartl FU, Behl C. 2009. Protein quality control during aging involves recruitment of the macroautophagy pathway by BAG3. Embo J 28:889-901.
[3] Morimoto RI. 2008. Proteotoxic stress and inducible chaperone networks in neurodegenerative disease and aging. Genes Dev 22:1427-1438.
[4] Crippa V, Sau D, Rusmini P, Boncoraglio A, Onesto E, Bolzoni E, Galbiati M, Fontana E, Marino M, Carra S, Bendotti C, De Biasi S, Poletti A. 2010. The small heat shock protein B8 (HspB8) promotes autophagic removal of misfolded proteins involved in amyotrophic lateral sclerosis (ALS). Human molecular genetics 19:3440-3456.
[5] Carra S, Crippa V, Rusmini P, Boncoraglio A, Minoia M, Giorgetti E, Kampinga HH, Poletti A. 2011. Alteration of protein folding and degradation in motor neuron diseases: Implications and protective functions of small heat shock proteins. Prog Neurobiol 97:83-100.
[6] Onesto E, Rusmini P, Crippa V, Ferri N, Zito A, Galbiati M, Poletti A. 2011. Muscle cells and motoneurons differentially remove mutant SOD1 causing familial amyotrophic lateral sclerosis. Journal of Neurochemistry 118: 266–280
MISFOLDING PROTEICO E NEURODEGENERAZIONE : STUDIO DEL COINVOLGIMENTO DELLA PROTEINA CHAPERONE HEAT SHOCK PROTEIN B8
No full textnul
An overview on some results concerning the transport equation and its applications to conservation laws
No full textNiguarda, un ospedale per l'uomo nel nuovo millennio. Arte e storia della cura alla Ca'Granda di Niguarda
No full textNon-uniqueness and prescribed energy for the continuity equation
No full textIn this note, we provide new non-uniqueness examples for the continuity equation by constructing infinitely many weak solutions with prescribed energy
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