Blocking IL-17: A Promising Strategy in the Treatment of Systemic Rheumatic Diseases

Systemic rheumatic diseases are a heterogeneous group of autoimmune disorders that affect the connective tissue, characterized by the involvement of multiple organs, leading to disability, organ failure and premature mortality. Despite the advances in recent years, the therapeutic options for these diseases are still limited and some patients do not respond to the current treatments. Interleukin-17 (IL-17) is a cytokine essential in the defense against extracellular bacteria and fungi. Disruption of IL-17 homeostasis has been associated with the development and progression of rheumatic diseases, and the approval of different biological therapies targeting IL-17 for the treatment of psoriatic arthritis (PsA) and ankylosing spondylitis (AS) has highlighted the key role of this cytokine. IL-17 has been also implicated in the pathogenesis of systemic rheumatic diseases, including systemic lupus erythematosus (SLE), Sjogren's syndrome (SS) and systemic sclerosis (SSc). The aim of this review is to summarize and discuss the most recent findings about the pathogenic role of IL-17 in systemic rheumatic and its potential use as a therapeutic option

Nonlinear saturation of electrostatic waves: mobile ions modify trapping scaling

The amplitude equation for an unstable electrostatic wave in a multi-species Vlasov plasma has been derived. The dynamics of the mode amplitude $\rho(t)$ is studied using an expansion in $\rho$; in particular, in the limit $\gamma\rightarrow0^+$, the singularities in the expansion coefficients are analyzed to predict the asymptotic dependence of the electric field on the linear growth rate $\gamma$. Generically $|E_k|\sim \gamma^{5/2}$, as $\gamma\rightarrow0^+$, but in the limit of infinite ion mass or for instabilities in reflection-symmetric systems due to real eigenvalues the more familiar trapping scaling $|E_k|\sim \gamma^{2}$ is predicted.Comment: 13 pages (Latex/RevTex), 4 postscript encapsulated figures which are included using the utility "uufiles". They should be automatically included with the text when it is downloaded. Figures also available in hard copy from the authors ([email protected]

Universal trapping scaling on the unstable manifold for a collisionless electrostatic mode

An amplitude equation for an unstable mode in a collisionless plasma is derived from the dynamics on the two-dimensional unstable manifold of the equilibrium. The mode amplitude $\rho(t)$ decouples from the phase due to the spatial homogeneity of the equilibrium, and the resulting one-dimensional dynamics is analyzed using an expansion in $\rho$. As the linear growth rate $\gamma$ vanishes, the expansion coefficients diverge; a rescaling $\rho(t)\equiv\gamma^2\,r(\gamma t)$ of the mode amplitude absorbs these singularities and reveals that the mode electric field exhibits trapping scaling $|E_1|\sim\gamma^2$ as $\gamma\rightarrow0$. The dynamics for $r(\tau)$ depends only on the phase $e^{i\xi}$ where $d\epsilon_{{k}} /dz=|{\epsilon_{{k}}}|e^{-i\xi/2}$ is the derivative of the dielectric as $\gamma\rightarrow0$.Comment: 11 pages (Latex/RevTex), 2 figures available in hard copy from the Author ([email protected]); paper accepted by Physical Review Letter

Universality classes in Burgers turbulence

We establish necessary and sufficient conditions for the shock statistics to approach self-similar form in Burgers turbulence with L\'{e}vy process initial data. The proof relies upon an elegant closure theorem of Bertoin and Carraro and Duchon that reduces the study of shock statistics to Smoluchowski's coagulation equation with additive kernel, and upon our previous characterization of the domains of attraction of self-similar solutions for this equation

Renormalizing Partial Differential Equations

In this review paper, we explain how to apply Renormalization Group ideas to the analysis of the long-time asymptotics of solutions of partial differential equations. We illustrate the method on several examples of nonlinear parabolic equations. We discuss many applications, including the stability of profiles and fronts in the Ginzburg-Landau equation, anomalous scaling laws in reaction-diffusion equations, and the shape of a solution near a blow-up point.Comment: 34 pages, Latex; [email protected]; [email protected]

Importância prognóstica do alelo CYP2C19*2 após uma síndrome coronária aguda: dados de um centro nacional

BACKGROUND: Clopidogrel requires oxidation dependent on the cytochrome P450 enzyme 2C19 (CYP2C19) to form its active metabolite. The importance of loss-of-function alleles (particularly CYP2C19*2, 681G>A) in poor platelet response to clopidogrel is well recognized. OBJECTIVE: To investigate the prevalence and prognostic impact of the CYP2C19*2 allele in a local acute coronary syndrome (ACS) population. METHODS: We performed a prospective, longitudinal study of 95 patients admitted for an ACS between March and October 2009 to a single coronary care unit. Patients aged under 75 who survived hospital stay and for whom clopidogrel was prescribed were included. At discharge, CYP2C19 was genotyped using a commercially available kit. Patients were divided into two groups: Group A (non-carriers, normal metabolizers, CYP2C19*1/*1), n=69; and Group B (carriers, slow metabolizers, CYP2C19*2/*1 or *2/*2), n=26. The primary endpoint was a combined outcome of cardiovascular death, non-fatal myocardial infarction or re-admission for unstable angina; median follow-up was 136.0 (79.0-188.0) days. RESULTS: The median age of the population was 62.0 (51.0-68.0) years, and 83.2% were male. The CYP2C19*2 (A) allele had a frequency of 14.2%. There were no differences between the groups with respect to demographic data or history of cardiovascular disease. Coronary anatomy, left ventricular ejection fraction and renal function were also similar. The groups were also homogenous with respect to GRACE risk score (118.0 (95.0-136.5) vs. 115.0 (96.0-133.0), p=0.68), medical treatment and percutaneous revascularization during hospital stay. Event-free survival was higher for Group A (94.0% vs. 75.0%, log-rank p=0.010). Three readmissions for MI were documented, all in the slow metabolizers group. CONCLUSION: In our ACS population, the CYP2C19*2 allele was a medium-term prognostic marker

Normal scaling in globally conserved interface-controlled coarsening of fractal clusters

Globally conserved interface-controlled coarsening of fractal clusters exhibits dynamic scale invariance and normal scaling. This is demonstrated by a numerical solution of the Ginzburg-Landau equation with a global conservation law. The sharp-interface limit of this equation is volume preserving motion by mean curvature. The scaled form of the correlation function has a power-law tail accommodating the fractal initial condition. The coarsening length exhibits normal scaling with time. Finally, shrinking of the fractal clusters with time is observed. The difference between global and local conservation is discussed.Comment: 4 pages, 3 eps figure

The phase shift of line solitons for the KP-II equation

The KP-II equation was derived by [B. B. Kadomtsev and V. I. Petviashvili,Sov. Phys. Dokl. vol.15 (1970), 539-541] to explain stability of line solitary waves of shallow water. Stability of line solitons has been proved by [T. Mizumachi, Mem. of vol. 238 (2015), no.1125] and [T. Mizumachi, Proc. Roy. Soc. Edinburgh Sect. A. vol.148 (2018), 149--198]. It turns out the local phase shift of modulating line solitons are not uniform in the transverse direction. In this paper, we obtain the $L^\infty$-bound for the local phase shift of modulating line solitons for polynomially localized perturbations

Nonlinear localized waves in a periodic medium

We analyze the existence and stability of nonlinear localized waves in a periodic medium described by the Kronig-Penney model with a nonlinear defect. We demonstrate the existence of a novel type of stable nonlinear band-gap localized states, and also reveal an important physical mechanism of the oscillatory wave instabilities associated with the band-gap resonances.Comment: 4 pages, 5 figure

A pilot study of a phenomenological model of adipogenesis in maturing adipocytes using Cahn–Hilliard theory

We consider the accumulation and formation of lipid droplets in an adipocyte cell. The process incorporates adipose nucleation (adipogenesis) and growth. At later stages, there will be merging of droplets and growth of larger droplets at the expense of the smaller droplets, which will essentially undergo lipolysis. The process is modeled by the use of the Cahn–Hilliard equation, which is mass-conserving and allows the formation of secondary phases in the context of spinodal decomposition. The volume of fluid (VOF) method is used to determine the total area that is occupied by the lipids in a given cross section. Further, we present an algorithm, applicable to all kinds of grids (structured or unstructured) in two spatial dimensions, to count the number of lipid droplets and the portion of the domain of computation that is occupied by the lipid droplets as a function of time during the process. The results are preliminary and are validated from a qualitative point using experiments carried out on cell cultures. It turns out that the Cahn–Hilliard theory can model many of the features during adipogenesis qualitatively