Training-induced criticality in martensites

We propose an explanation for the self-organization towards criticality observed in martensites during the cyclic process known as `training'. The scale-free behavior originates from the interplay between the reversible phase transformation and the concurrent activity of lattice defects. The basis of the model is a continuous dynamical system on a rugged energy landscape, which in the quasi-static limit reduces to a sandpile automaton. We reproduce all the principal observations in thermally driven martensites, including power-law statistics, hysteresis shakedown, asymmetric signal shapes, and correlated disorder.Comment: 5 pages, 4 figure

Social cognition in multiple sclerosis: a 3-year follow-up {MRI} and behavioral study

Social cognition (SC) has become a topic of widespread interest in the last decade. SC deficits were described in multiple sclerosis (MS) patients, in association with amygdala lesions, even in those without formal cognitive impairment. In this 3-year follow-up study, we aimed at longitudinally investigating the evolution of SC deficits and amygdala damage in a group of cognitive-normal MS patients, and the association between SC and psychological well-being. After 3 years (T3) from the baseline examination (T0), 26 relapsing-remitting MS patients (RRMS) were retested with a neuropsychological battery and SC tasks (theory of mind, facial emotion recognition, empathy). A SC composite score (SCcomp) was calculated for each patient. Emotional state, fatigue, and quality of life (QoL) were also evaluated. RRMS patients at T3 underwent a 3T-MRI as performed at T0, from which were calculated both volume and cortical lesion volume (CLV) of the amygdalae. Compared to T0, at T3 all RRMS patients were still cognitive-normal and remained stable in their global SC impaired performance. At T0, SCcomp correlated with amygdala CLV (p = 0.002) while, at T3, was more associated with amygdala volume (p = 0.035) rather than amygdala CLV (p = 0.043). SCcomp change T3-T0 correlated with global emotional state (p = 0.043), depression (p = 0.046), anxiety (p = 0.034), fatigue (p = 0.025), and QoL-social functioning (p = 0.033). We showed the longitudinal stability of SC deficits in cognitive-normal RRMS patients, mirroring the amygdala structural damage and the psychological well-being. These results highlight that SC exerts a key role in M

Homogenization in magnetic-shape-memory polymer composites

Magnetic-shape-memory materials (e.g. specific NiMnGa alloys) react with a large change of shape to the presence of an external magnetic field. As an alternative for the difficult to manifacture single crystal of these alloys we study composite materials in which small magnetic-shape-memory particles are embedded in a polymer matrix. The macroscopic properties of the composite depend strongly on the geometry of the microstructure and on the characteristics of the particles and the polymer. We present a variational model based on micromagnetism and elasticity, and derive via homogenization an effective macroscopic model under the assumption that the microstructure is periodic. We then study numerically the resulting cell problem, and discuss the effect of the microstructure on the macroscopic material behavior. Our results may be used to optimize the shape of the particles and the microstructure.Comment: 17 pages, 4 figure

Increase of CSF inflammatory profile in a case of highly active multiple sclerosis

BACKGROUND: Clinical and imaging follow-up coupled with cerebrospinal fluid (CSF) and possibly serum profiling could provide information on disease activity and disability evolution in multiple sclerosis patients. CASE PRESENTATION: We describe the case of a relapsing-remitting MS patient whose history was characterized by failure of several therapeutic approaches and sustained disease activity. By using a highly sensitive immunoassay methodology, we examined protein expression of 70 inflammatory/cytotoxic molecules in two consecutive paired CSF and serum samples, obtained respectively in 2006 and 2013. At disease diagnosis, elevated CSF protein levels of an inflammatory pattern, including CXCL13, CXCL12, IFNγ, TNF, sTNFR1, IL8, sCD163, APRIL, BAFF, pentraxin III and MMP2 were found compared with a group of controls. At the second lumbar puncture, sustained disease activity was accompanied by considerable (more than 2 fold changes) increase expression of most of these inflammatory molecules while no significant changes in serum inflammatory markers were detected in the two consecutive serum samples. CONCLUSIONS: Elevated CSF protein expression of pro-inflammatory mediators, possibly specifically associated to GM demyelination, could remain stable or increase over time in patients with active multiple sclerosis. We underline the role of fluid analysis in understanding the pathophysiology of the disease and providing information on possible markers of disease activity and evolution

Heterogeneity of Cortical Lesion Susceptibility Mapping in Multiple Sclerosis.

BACKGROUND AND PURPOSE: Quantitative susceptibility mapping has been used to characterize iron and myelin content in the deep gray matter of patients with multiple sclerosis. Our aim was to characterize the susceptibility mapping of cortical lesions in patients with MS and compare it with neuropathologic observations. MATERIALS AND METHODS: The pattern of microglial activation was studied in postmortem brain tissues from 16 patients with secondary-progressive MS and 5 age-matched controls. Thirty-six patients with MS underwent 3T MR imaging, including 3D double inversion recovery and 3D-echo-planar SWI. RESULTS: Neuropathologic analysis revealed the presence of an intense band of microglia activation close to the pial membrane in subpial cortical lesions or to the WM border of leukocortical cortical lesions. The quantitative susceptibility mapping analysis revealed 131 cortical lesions classified as hyperintense; 33, as isointense; and 84, as hypointense. Quantitative susceptibility mapping hyperintensity edge found in the proximity of the pial surface or at the white matter/gray matter interface in some of the quantitative susceptibility mapping–hyperintense cortical lesions accurately mirrors the microglia activation observed in the neuropathology analysis. CONCLUSIONS: Cortical lesion susceptibility maps are highly heterogeneous, even at individual levels. Quantitative susceptibility mapping hyperintensity edge found in proximity to the pial surface might be due to the subpial gradient of microglial activation

Modelling avalanches in martensites

Solids subject to continuous changes of temperature or mechanical load often exhibit discontinuous avalanche-like responses. For instance, avalanche dynamics have been observed during plastic deformation, fracture, domain switching in ferroic materials or martensitic transformations. The statistical analysis of avalanches reveals a very complex scenario with a distinctive lack of characteristic scales. Much effort has been devoted in the last decades to understand the origin and ubiquity of scale-free behaviour in solids and many other systems. This chapter reviews some efforts to understand the characteristics of avalanches in martensites through mathematical modelling.Comment: Chapter in the book "Avalanches in Functional Materials and Geophysics", edited by E. K. H. Salje, A. Saxena, and A. Planes. The final publication is available at Springer via http://dx.doi.org/10.1007/978-3-319-45612-6_

CSF parvalbumin levels reflect interneuron loss linked with cortical pathology in multiple sclerosis

INTRODUCTION AND METHODS: In order to verify whether parvalbumin (PVALB), a protein specifically expressed by GABAergic interneurons, could be a MS-specific marker of grey matter neurodegeneration, we performed neuropathology/molecular analysis of PVALB expression in motor cortex of 40 post-mortem progressive MS cases, with/without meningeal inflammation, and 10 control cases, in combination with cerebrospinal fluid (CSF) assessment. Analysis of CSF PVALB and neurofilaments (Nf-L) levels combined with physical/cognitive/3TMRI assessment was performed in 110 naïve MS patients and in 32 controls at time of diagnosis. RESULTS: PVALB gene expression was downregulated in MS (fold change = 3.7 ± 1.2, P < 0.001 compared to controls) reflecting the significant reduction of PVALB+ cell density in cortical lesions, to a greater extent in MS patients with high meningeal inflammation (51.8, P < 0.001). Likewise, post-mortem CSF-PVALB levels were higher in MS compared to controls (fold change = 196 ± 36, P < 0.001) and correlated with decreased PVALB+ cell density (r = -0.64, P < 0.001) and increased MHC-II+ microglia density (r = 0.74, P < 0.01), as well as with early age of onset (r = -0.69, P < 0.05), shorter time to wheelchair (r = -0.49, P < 0.05) and early age of death (r = -0.65, P < 0.01). Increased CSF-PVALB levels were detected in MS patients at diagnosis compared to controls (P = 0.002). Significant correlation was found between CSF-PVALB levels and cortical lesion number on MRI (R = 0.28, P = 0.006) and global cortical thickness (R = -0.46, P < 0.001), better than Nf-L levels. CSF-PVALB levels increased in MS patients with severe cognitive impairment (mean ± SEM:25.2 ± 7.5 ng/mL) compared to both cognitively normal (10.9 ± 2.4, P = 0.049) and mild cognitive impaired (10.1 ± 2.9, P = 0.024) patients. CONCLUSIONS: CSF-PVALB levels reflect loss of cortical interneurons in MS patients with more severe disease course and might represent an early, new MS-specific biomarker of cortical neurodegeneration, atrophy, and cognitive decline

Proteomic Analysis of Ovarian Cancer Cells Reveals Dynamic Processes of Protein Secretion and Shedding of Extra-Cellular Domains

Background: Elucidation of the repertoire of secreted and cell surface proteins of tumor cells is relevant to molecular diagnostics, tumor imaging and targeted therapies. We have characterized the cell surface proteome and the proteins released into the extra-cellular milieu of three ovarian cancer cell lines, CaOV3, OVCAR3 and ES2 and of ovarian tumor cells enriched from ascites fluid. Methodology and Findings: To differentiate proteins released into the media from protein constituents of media utilized for culture, cells were grown in the presence of [ 13 C]-labeled lysine. A biotinylation-based approach was used to capture cell surface associated proteins. Our general experimental strategy consisted of fractionation of proteins from individual compartments followed by proteolytic digestion and LC-MS/MS analysis. In total, some 6,400 proteins were identified with high confidence across all specimens and fractions. Conclusions and Significance: Protein profiles of the cell lines had substantial similarity to the profiles of human ovarian cancer cells from ascites fluid and included protein markers known to be associated with ovarian cancer. Proteomic analysis indicated extensive shedding from extra-cellular domains of proteins expressed on the cell surface, and remarkably high secretion rates for some proteins (nanograms per million cells per hour). Cell surface and secreted proteins identified by indept

A Mouse to Human Search for Plasma Proteome Changes Associated with Pancreatic Tumor Development

Background: The complexity and heterogeneity of the human plasma proteome have presented significant challenges in the identification of protein changes associated with tumor development. Refined genetically engineered mouse (GEM) models of human cancer have been shown to faithfully recapitulate the molecular, biological, and clinical features of human disease. Here, we sought to exploit the merits of a well-characterized GEM model of pancreatic cancer to determine whether proteomics technologies allow identification of protein changes associated with tumor development and whether such changes are relevant to human pancreatic cancer. Methods and Findings: Plasma was sampled from mice at early and advanced stages of tumor development and from matched controls. Using a proteomic approach based on extensive protein fractionation, we confidently identified 1,442 proteins that were distributed across seven orders of magnitude of abundance in plasma. Analysis of proteins chosen on the basis of increased levels in plasma from tumor-bearing mice and corroborating protein or RNA expression in tissue documented concordance in the blood from 30 newly diagnosed patients with pancreatic cancer relative to 30 control specimens. A panel of five proteins selected on the basis of their increased level at an early stage of tumor development in the mouse was tested in a blinded study in 26 humans from the CARET (Carotene and Retinol Efficacy Trial) cohort. The panel discriminated pancreatic cancer cases from matched controls in blood specimens obtained between 7 and 13 mo prior to the development of symptoms and clinical diagnosis of pancreatic cancer. Conclusions: Our findings indicate that GEM models of cancer, in combination with in-depth proteomic analysis, provide a useful strategy to identify candidate markers applicable to human cancer with potential utility for early detection