Ultrametric Logarithm Laws, II

We prove positive characteristic versions of the logarithm laws of Sullivan and Kleinbock-Margulis and obtain related results in Metric Diophantine Approximation.Comment: submitted to Montasefte Fur Mathemati

Paradoxical aortic stiffening and subsequent cardiac dysfunction in Hutchinson-Gilford progeria syndrome

[EN] Hutchinson-Gilford progeria syndrome (HGPS) is an ultra-rare disorder with devastating sequelae resulting in early death, presently thought to stem primarily from cardiovascular events. We analyse novel longitudinal cardiovascular data from a mouse model of HGPS (Lmna(G609G/G609G)) using allometric scaling, biomechanical phenotyping, and advanced computational modelling and show that late-stage diastolic dysfunction, with preserved systolic function, emerges with an increase in the pulse wave velocity and an associated loss of aortic function, independent of sex. Specifically, there is a dramatic late-stage loss of smooth muscle function and cells and an excessive accumulation of proteoglycans along the aorta, which result in a loss of biomechanical function (contractility and elastic energy storage) and a marked structural stiffening despite a distinctly low intrinsic material stiffness that is consistent with the lack of functional lamin A. Importantly, the vascular function appears to arise normally from the low-stress environment of development, only to succumb progressively to pressure-related effects of the lamin A mutation and become extreme in the peri-morbid period. Because the dramatic life-threatening aortic phenotype manifests during the last third of life there may be a therapeutic window in maturity that could alleviate concerns with therapies administered during early periods of arterial development.This work was supported, in part, by grants from the US National Institutes of Health: R01 HL105297 (J.D.H.) and P01 HL134605 (Dan Rifkin) and R01 AG047632 and R33 ES025636 (G.S.S.)Murtada, SI.; Kawamura, Y.; Caulk, AW.; Ahmadzadeh, H.; Mikush, N.; Zimmerman, K.; Kavanagh, D.... (2020). Paradoxical aortic stiffening and subsequent cardiac dysfunction in Hutchinson-Gilford progeria syndrome. Journal of The Royal Society Interface. 17(166):1-12. https://doi.org/10.1098/rsif.2020.00661121716

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

Naturally propped fractures caused by quartz cementation preserve oil reservoirs in basement rocks

MB is in receipt of a postgraduate studentship from PTDF (Nigeria). Skilled technical support was provided by M. Baron and J. Still. Two reviewers made valuable criticisms that improved the paper.Peer reviewedPostprin