CDKN2A/p16INK4a expression is associated with vascular progeria in chronic kidney disease

Patients with chronic kidney disease (CKD) display a progeric vascular phenotype linked to apoptosis, cellular senescence and osteogenic transformation. This has proven intractable to modelling appropriately in model organisms. We have therefore investigated this directly in man, using for the first time validated cellular biomarkers of ageing (CDKN2A/p16INK4a, SA-β-Gal) in arterial biopsies from 61 CKD patients undergoing living donor renal transplantation. We demonstrate that in the uremic milieu, increased arterial expression of CDKN2A/p16INK4a associated with vascular progeria in CKD, independently of chronological age. The arterial expression of CDKN2A/p16INK4a was significantly higher in patients with coronary calcification (p=0.01) and associated cardiovascular disease (CVD) (p=0.004). The correlation between CDKN2A/p16INK4a and media calcification was statistically significant (p=0.0003) after correction for chronological age. We further employed correlate expression of matrix Gla protein (MGP) and runt-related transcription factor 2 (RUNX2) as additional pathognomonic markers. Higher expression of CDKN2A/p16INK4a, RUNX2 and MGP were observed in arteries with severe media calcification. The number of p16INK4a and SA-β-Gal positive cells was higher in biopsies with severe media calcification. A strong inverse correlation was observed between CDKN2A/p16INK4a expression and carboxylated osteocalcin levels. Thus, impaired vitamin K mediated carboxylation may contribute to premature vascular senescence

The double torus as a 2D cosmos: groups, geometry and closed geodesics

The double torus provides a relativistic model for a closed 2D cosmos with topology of genus 2 and constant negative curvature. Its unfolding into an octagon extends to an octagonal tessellation of its universal covering, the hyperbolic space H^2. The tessellation is analysed with tools from hyperbolic crystallography. Actions on H^2 of groups/subgroups are identified for SU(1, 1), for a hyperbolic Coxeter group acting also on SU(1, 1), and for the homotopy group \Phi_2 whose extension is normal in the Coxeter group. Closed geodesics arise from links on H^2 between octagon centres. The direction and length of the shortest closed geodesics is computed.Comment: Latex, 27 pages, 5 figures (late submission to arxiv.org

Deuterated molecules in regions of high-mass star formation

We present the results of our studies of deuterated molecules (DCN, DNC, DCO$^+$, N$_2$D$^+$ and NH$_2$D) in regions of high-mass star formation, which include a survey of such regions with the 20-m Onsala radio telescope and mapping of several objects in various lines with the 30-m IRAM and 100-m MPIfR radio telescopes. The deuteration degree reaches $\sim$10$^{-2}$ in these objects. We discuss its dependencies on the gas temperature and velocity dispersion, as well as spatial distributions of deuterated molecules. We show that the H$^{13}$CN/HN$^{13}$C intensity ratio may be a good indicator of the gas kinetic temperature and estimate densities of the investigated objects.Comment: 8 pages, 4 figures, to be published in Proceedings of Science (Proceedings of the conference "The Multifaceted Universe: Theory and Observations - 2022", 23-27 May 2022, SAO RAS, Nizhny Arkhyz, Russia

Efficiency of a gyroscopic device for conversion of mechanical wave energy to electrical energy:Technical report from ESGI-83 workshop in industrial mathematics 2011

We consider a recently proposed gyroscopic device for conversion of mechanical ocean wave energy to electrical energy. Two models of the device derived from standard engineering mechanics from the literature are analysed, and a model is derived from analytical mechanics considerations. From these models, estimates of the power production, efficiency, forces and moments are made. We find that it is possible to extract a significant amount of energy from an ocean wave using the described device. Further studies are required for a full treatment of the device.Resulting from the interaction with Joltech A/S at ESGI-83 (European Study Group with Industry) workshop on industrial mathematics, Sønderborg Denmark, 2011.</p

Quantifying the Lobe Reconnection Rate During Dominant IMF By Periods and Different Dipole Tilt Orientations

Lobe reconnection is usually thought to play an important role in geospace dynamics only when the Interplanetary Magnetic Field (IMF) is mainly northward. This is because the most common and unambiguous signature of lobe reconnection is the strong sunward convection in the polar cap ionosphere observed during these conditions. During more typical conditions, when the IMF is mainly oriented in a dawn-dusk direction, plasma flows initiated by dayside and lobe reconnection both map to high-latitude ionospheric locations in close proximity to each other on the dayside. This makes the distinction of the source of the observed dayside polar cap convection ambiguous, as the flow magnitude and direction are similar from the two topologically different source regions. We here overcome this challenge by normalizing the ionospheric convection observed by the Super Dual Aurora Radar Network (SuperDARN) to the polar cap boundary, inferred from simultaneous observations from the Active Magnetosphere and Planetary Electrodynamics Response Experiment (AMPERE). This new method enable us to separate and quantify the relative contribution of both lobe reconnection and dayside/nightside (Dungey cycle) reconnection during periods of dominating IMF By. Our main findings are twofold. First, the lobe reconnection rate can typically account for 20% of the Dungey cycle flux transport during local summer when IMF By is dominating and IMF Bz ≥ 0. Second, the dayside convection relative to the open/closed boundary is vastly different in local summer versus local winter, as defined by the dipole tilt angle.publishedVersio

Inflammation and premature ageing in chronic kidney disease

Persistent low-grade inflammation and premature ageing are hallmarks of the uremic phenotype and contribute to impaired health status, reduced quality of life, and premature mortality in chronic kidney disease (CKD). Because there is a huge global burden of disease due to CKD, treatment strategies targeting inflammation and premature ageing in CKD are of particular interest. Several distinct features of the uremic phenotype may represent potential treatment options to attenuate the risk of progression and poor outcome in CKD. The nuclear factor erythroid 2-related factor 2 (NRF2)−kelch-like erythroid cell-derived protein with CNC homology [ECH]-associated protein 1 (KEAP1) signaling pathway, the endocrine phosphate-fibroblast growth factor-23−klotho axis, increased cellular senescence, and impaired mitochondrial biogenesis are currently the most promising candidates, and different pharmaceutical compounds are already under evaluation. If studies in humans show beneficial effects, carefully phenotyped patients with CKD can benefit from them

An Observed Correlation Between Thermal and Non-Thermal Emission in Gamma-Ray Bursts

Recent observations by the $Fermi$ Gamma-ray Space Telescope have confirmed the existence of thermal and non-thermal components in the prompt photon spectra of some Gamma-ray bursts (GRBs). Through an analysis of six bright Fermi GRBs, we have discovered a correlation between the observed photospheric and non-thermal $\gamma$-ray emission components of several GRBs using a physical model that has previously been shown to be a good fit to the Fermi data. From the spectral parameters of these fits we find that the characteristic energies, $E_{\rm p}$ and $kT$, of these two components are correlated via the relation $E_{\rm p} \propto T^{\alpha}$ which varies from GRB to GRB. We present an interpretation in which the value of index $\alpha$ indicates whether the jet is dominated by kinetic or magnetic energy. To date, this jet composition parameter has been assumed in the modeling of GRB outflows rather than derived from the data

Rice farming systems in Southern Lao PDR: Interpreting farmers’ agricultural production decisions using Q methodology

© 2017 The agricultural sector in Lao PDR is forecast to move from subsistence rice production to a more modernized and market-oriented sector with greater focus on commercialization of agricultural production. Intensification of agricultural production in the southern and central rice growing regions of Lao PDR is problematic as dryland farmers rely on rainfall and soils are poor, yet rural households have been experiencing rapid change in their farming and livelihood systems. This paper employs Q methodology techniques to explore 35 farmers' viewpoints when contemplating their production goals and potential to adopt technologies to improve productivity. Findings describe the two emerging viewpoints among farmers as ‘labour saving productivity maximization’ and ‘traditional labour productivity using improved techniques’. The two viewpoints describe the different issues currently guiding production decisions. While the Lao Government forecasts substantial increases in rice production in the southern plains, farmers will require specialized and tailored support, accounting for their envisaged livelihood and production goals, to allow the sector transformation that many stakeholders currently envisage