Excessive adventitial stress drives inflammation-mediated fibrosis in hypertensive aortic remodelling in mice

Hypertension induces significant aortic remodeling, often adaptive but sometimes not. To identify immuno-mechanical mechanisms responsible for differential remodeling, we studied thoracic aortas from 129S6/SvEvTac and C57BL/6J mice before and after continuous 14-day angiotensin II infusion, which elevated blood pressure similarly in both strains. Histological and biomechanical assessments of excised vessels were similar at baseline, suggesting a common homeostatic set-point for mean wall stress. Histology further revealed near mechano-adaptive remodeling of the hypertensive 129S6/SvEvTac aortas, but grossly maladaptive remodeling of C57BL/6J aortas. Bulk RNA sequencing suggested that increased smooth muscle contractile processes promoted mechano-adaptation of 129S6/SvEvTac aortas while immune processes prevented adaptation of C57BL/6J aortas. Functional studies confirmed an increased vasoconstrictive capacity of the former while immunohistochemistry demonstrated marked increases in inflammatory cells in the latter. We then used multiple computational biomechanical models to test the hypothesis that excessive adventitial wall stress correlates with inflammatory cell infiltration. These models consistently predicted that increased vasoconstriction against an increased pressure coupled with modest deposition of new matrix thickens the wall appropriately, restoring wall stress toward homeostatic consistent with adaptive remodeling. In contrast, insufficient vasoconstriction permits high wall stresses and exuberant inflammation-driven matrix deposition, especially in the adventitia, reflecting compromised homeostasis and gross maladaptation

Many body physics from a quantum information perspective

The quantum information approach to many body physics has been very successful in giving new insight and novel numerical methods. In these lecture notes we take a vertical view of the subject, starting from general concepts and at each step delving into applications or consequences of a particular topic. We first review some general quantum information concepts like entanglement and entanglement measures, which leads us to entanglement area laws. We then continue with one of the most famous examples of area-law abiding states: matrix product states, and tensor product states in general. Of these, we choose one example (classical superposition states) to introduce recent developments on a novel quantum many body approach: quantum kinetic Ising models. We conclude with a brief outlook of the field.Comment: Lectures from the Les Houches School on "Modern theories of correlated electron systems". Improved version new references adde

Functionality, reliability and adaptability improvements to the OSSIM information security console

Security consoles are among the most widely deployed tools for information security management in today's organizations. This article summarizes the work of our research team, in order to incorporate several enhancements to the OSSIM information security console. Such enhancements include integration with physical security control devices, automatic creation of correlation directives for OSSIM's correlation engine, and a significant improvement in information capture reliability on high-traffic networks. © 2009 IEEE

Interacting slow and fast dynamics in precise spiking-bursting neurons

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Hereditary Leiomyomatosis and Renal Cell Cancer Syndrome in Spain: Clinical and Genetic Characterization

Hereditary leiomyomatosis and renal cell cancer syndrome (HLRCC) is a very rare hereditary disorder characterized by cutaneous leiomyomas (CLMs), uterine leiomyomas (ULMs), renal cysts (RCys) and renal cell cancers (RCCs). We aimed to describe the genetics, clinical features and potential genotype-phenotype associations in the largest cohort of fumarate hydratase enzyme mutation carriers known from Spain using a multicentre, retrospective study of individuals with a genetic or clinical diagnosis of HLRCC. We collected clinical information from medical records, analysed genetic variants and looked for genotype-phenotype associations. Analyses were performed using R 3.6.0. software. We included 197 individuals: 74 index cases and 123 relatives. CLMs were diagnosed in 65% of patients, ULMs in 90% of women, RCys in 37% and RCC in 10.9%. Twenty-seven different pathogenic variants were detected, 12 (44%) of them not reported previously. Patients with missense pathogenic variants showed higher frequencies of CLMs, ULMs and RCys, than those with loss-of-function variants (p = 0.0380, p = 0.0015 and p = 0.024, respectively). This is the first report of patients with HLRCC from Spain. The frequency of RCCs was lower than those reported in the previously published series. Individuals with missense pathogenic variants had higher frequencies of CLMs, ULMs and RCys