Long time dynamics of solutions to pp-Laplacian diffusion problems with bistable reaction terms

This paper establishes the emergence of slowly moving transition layer solutions for the $p$-Laplacian (nonlinear) evolution equation, $$u_t = \varepsilon^p(|u_x|^{p-2}u_x)_x - F'(u), \qquad x \in (a,b), \; t > 0,$$ where $\varepsilon>0$ and $p>1$ are constants, driven by the action of a family of double-well potentials of the form $$F(u)=\frac{1}{2n} |1-u^2|^{n},$$ indexed by $n>1$, $n\in\mathbb{R}$ with minima at two pure phases $u = \pm 1$. The equation is endowed with initial conditions and boundary conditions of Neumann type. It is shown that interface layers, or solutions which initially are equal to $\pm 1$ except at a finite number of thin transitions of width $\varepsilon$, persist for an exponentially long time in the critical case with $n=p$, and for an algebraically long time in the supercritical (or degenerate) case with $n > p$. For that purpose, energy bounds for a renormalized effective energy potential of Ginzburg-Landau type are established. In contrast, in the subcritical case with $n<p$, the transition layer solutions are stationary.Comment: 29 pages, 5 figure

Metastable patterns for a reaction-diffusion model with mean curvature-type diffusion

Reaction-diffusion equations are widely used to describe a variety of phenomena such as pattern formation and front propagation in biological, chemical and physical systems. In the one-dimensional model with a balanced bistable reaction function, it is well-known that there is persistence of metastable patterns for an exponentially long time, i.e. a time proportional to \exp(C/\e) where C,\e are strictly positive constants and \e^2 is the diffusion coefficient. In this paper, we extend such results to the case when the linear diffusion flux is substituted by the mean curvature operator both in Euclidean and Lorentz--Minkowski spaces. More precisely, for both models, we prove existence of metastable states which maintain a transition layer structure for an exponentially long time and we show that the speed of the layers is exponentially small. Numerical simulations, which confirm the analytical results, are also provided.Comment: 27 pages, 5 figure

Experimental and Simulation Study of Adsorption in Postcombustion Conditions Using a Microporous Biochar. 1. CO2 and N2 Adsorption

The influence of N2 on CO2 adsorption was evaluated using a microporous biochar with a narrow pore size distribution. The adsorption isotherms of pure CO2 and N2 were measured at 0, 30, 50, and 70 °C up to 120 kPa and fitted to the Toth adsorption model. Dynamic breakthrough experiments were carried out in a fixed-bed adsorption unit using binary mixtures with compositions representative of different postcombustion streams (8–30% CO2) from ambient temperature to 70 °C. Dynamic adsorption experiments were simulated to validate the mathematical model of the adsorption process, as a necessary step for its later use for process design. The Ideal Adsorption Solution (IAS) theory, based on the pure component adsorption models, was used to account for competitive adsorption with satisfactory results. The information gathered in the present work will be used to extend the validity of the model to the adsorption of postcombustion streams containing H2O in part 2.Work was carried out with financial support from the HiPerCap Project of the European Union 7th Framework Programme FP7 (2007-2013; Grant Agreement number: 60855). M.G.P. acknowledges funding from the CSIC (JAE-Doc program cofinanced by the European Social Fund). N.Q. acknowledges funding from the Government of the Principado de Asturias (Severo Ochoa Program). The authors also appreciate the support from the technical consultants of AspenTechnology Inc., M.M. and E.L.Peer reviewe

An allosteric switch between the activation loop and a c-terminal palindromic phosphomotif controls c-Src function.

Autophosphorylation controls the transition between discrete functional and conformational states in protein kinases, yet the structural and molecular determinants underlying this fundamental process remain unclear. Here we show that c-terminal Tyr 530 is a de facto c-Src autophosphorylation site with slow time-resolution kinetics and a strong intermolecular component. On the contrary, activation-loop Tyr 419 undergoes faster kinetics and a cis-to-trans phosphorylation switch that controls c-terminal Tyr 530 autophosphorylation, enzyme specificity, and strikingly, c-Src non-catalytic function as a substrate. In line with this, we visualize by X-ray crystallography a snapshot of Tyr 530 intermolecular autophosphorylation. In an asymmetric arrangement of both catalytic domains, a c-terminal palindromic phospho-motif flanking Tyr 530 on the substrate molecule engages the G-loop of the active kinase adopting a position ready for entry into the catalytic cleft. Perturbation of the phosphomotif accounts for c-Src dysfunction as indicated by viral and colorectal cancer (CRC)-associated c-terminal deleted variants.Weshow that c-terminal residues 531 to 536 are required for c-Src Tyr 530 autophosphorylation, and such a detrimental effect is caused by the substrate molecule inhibiting allosterically the active kinase. Our work reveals a crosstalk between the activation and c-terminal segments that control the allosteric interplay between substrateand enzyme-acting kinases during autophosphorylation.post-print5137 K

Mate Value and Self-Esteem: Evidence from Eight Cultural Groups

This paper explores self-perceived mate value (SPMV), and its association with self-esteem, in eight cultures. 1066 participants, from 8 cultural groups in 7 countries, rated themselves on 24 SPMVs and completed a measure of self-esteem. Consistent with evolutionary theory, women were more likely to emphasise their caring and passionate romantic nature. In line with previous cross-cultural research, characteristics indicating passion and romance and social attractiveness were stressed more by respondents from individualistic cultures, and those higher on self-expression (rather than survival) values; characteristics indicative of maturity and confidence were more likely to be mentioned by those from Traditional, rather than Secular, cultures. Contrary to gender role theory, societal equality had only limited interactions with sex and SPMV, with honesty of greater significance for male self-esteem in societies with unequal gender roles. These results point to the importance of cultural and environmental factors in influencing self-perceived mate qualities, and are discussed in relation to broader debates about the impact of gender role equality on sex differences in personality and mating strategies

Canagliflozin and renal outcomes in type 2 diabetes and nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to &lt;90 ml per minute per 1.73 m2 of body-surface area and albuminuria (ratio of albumin [mg] to creatinine [g], &gt;300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of &lt;15 ml per minute per 1.73 m2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P&lt;0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P&lt;0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

TCTEX1D2 mutations underlie Jeune asphyxiating thoracic dystrophy with impaired retrograde intraflagellar transport

Tiina Paunio on työryhmän UK10K jäsen.The analysis of individuals with ciliary chondrodysplasias can shed light on sensitive mechanisms controlling ciliogenesis and cell signalling that are essential to embryonic development and survival. Here we identify TCTEX1D2 mutations causing Jeune asphyxiating thoracic dystrophy with partially penetrant inheritance. Loss of TCTEX1D2 impairs retrograde intraflagellar transport (IFT) in humans and the protist Chlamydomonas, accompanied by destabilization of the retrograde IFT dynein motor. We thus define TCTEX1D2 as an integral component of the evolutionarily conserved retrograde IFT machinery. In complex with several IFT dynein light chains, it is required for correct vertebrate skeletal formation but may be functionally redundant under certain conditions.Peer reviewe