A1A_1 theory of weights for rough homogeneous singular integrals and commutators

Quantitative $A_1-A_\infty$ estimates for rough homogeneous singular integrals $T_{\Omega}$ and commutators of $BMO$ symbols and $T_{\Omega}$ are obtained. In particular the following estimates are proved: % $$\|T_\Omega \|_{L^p(w)}\le c_{n,p}\|\Omega\|_{L^\infty} [w]_{A_1}^{\frac{1}{p}}\,[w]_{A_{\infty}}^{1+\frac{1}{p'}}\|f\|_{L^p(w)}$$ % and % $$\| [b,T_{\Omega}]f\|_{L^{p}(w)}\leq c_{n,p}\|b\|_{BMO}\|\Omega\|_{L^{\infty}} [w]_{A_1}^{\frac{1}{p}}[w]_{A_{\infty}}^{2+\frac{1}{p'}}\|f\|_{L^{p}\left(w\right)},$$ % for $1<p<\infty$ and $1/p+1/p'=1$.Comment: 19 page

A1A_1 theory of weights for rough homogeneous singular integrals and commutators

Quantitative $A_1-A_\infty$ estimates for rough homogeneous singular integrals $T_{\Omega}$ and commutators of \BMO symbols and $T_{\Omega}$ are obtained. In particular the following estimates are proved: $$\|T_\Omega \|_{L^p(w)}\le c_{n,p}\|\Omega\|_{L^\infty} [w]_{A_1}^{\frac{1}{p}}\,[w]_{A_{\infty}}^{1+\frac{1}{p'}}\|f\|_{L^p(w)}$$ and \| [b,T_{\Omega}]f\| _{L^{p}(w)}\leq c_{n,p}\|b\|_{\BMO}\|\Omega\|_{L^{\infty}} [w]_{A_1}^{\frac{1}{p}}[w]_{A_{\infty}}^{2+\frac{1}{p'}}\|f\|_{L^{p}\left(w\right)}, for $1<p<\infty$ and $1/p+1/p'=1$.BERC 2014-2017 BCAM Severo Ochoa excellence accreditation SEV-2013-0323 MTM2014-53850-P. MTM2015-65888-C04-4-P 2017 Leonardo grant for Researchers and Cultural Creators, BBVA Foundatio

Weighted norm inequalities for rough singular integral operators

In this paper we provide weighted estimates for rough operators, including rough homogeneous singular integrals $T_\Omega$ with $\Omega\in L^\infty(\mathbb{S}^{n-1})$ and the Bochner--Riesz multiplier at the critical index $B_{(n-1)/2}$. More precisely, we prove qualitative and quantitative versions of Coifman--Fefferman type inequalities and their vector-valued extensions, weighted $A_p-A_\infty$ strong and weak type inequalities for $1<p<\infty$, and $A_1-A_\infty$ type weak $(1,1)$ estimates. Moreover, Fefferman--Stein type inequalities are obtained, proving in this way a conjecture raised by the second-named author in the 90's. As a corollary, we obtain the weighted $A_1-A_\infty$ type estimates. Finally, we study rough homogenous singular integrals with a kernel involving a function $\Omega\in L^q(\mathbb{S}^{n-1})$, $1<q<\infty$, and provide Fefferman--Stein inequalities too. The arguments used for our proofs combine several tools: a recent sparse domination result by Conde--Alonso et al. \cite{CACDPO}, results by the first author in \cite{L}, suitable adaptations of Rubio de Francia algorithm, the extrapolation theorems for $A_{\infty}$ weights \cite{CMP,CGMP} and ideas contained in previous works by A. Seeger in \cite{S} and D. Fan and S. Sato \cite{FS}.Juan de la Cierva - Formaci\'on 2015 FJCI-2015-24547. BBVA Foundatio

The 4G/5G PAI-1 polymorphism influences the endothelial response to IL-1 and the modulatory effect of pravastatin

BACKGROUND: Increased plasminogen activator inhibitor (PAI-1) levels lead to impaired fibrinolytic function associated with higher cardiovascular risk. PAI-1 expression may be regulated by different inflammatory cytokines such as interleukin-1alpha (IL-1). Several polymorphisms have been described in the PAI-1 gene. AIM: We examined the influence of the 4G/5G polymorphism in the promoter region on IL-1alpha-induced PAI-1 expression by human umbilical vein endothelial cells (HUVEC) in presence or absence of pravastatin. METHODS AND RESULTS: Genotyped HUVEC were incubated with IL-1alpha (500 U mL(-1)) in presence or absence of pravastatin (1-10 microm). PAI-1 expression was analyzed by real time polymerase chain reaction (PCR), and PAI-1 antigen measured in supernatants by ELISA. IL-1alpha increased PAI-1 secretion in a genotype-dependent manner, and higher values were observed for 4G/4G compared with both 4G/5G and 5G/5G cultures (P < 0.05). Preincubation of HUVEC with 10 microm pravastatin significantly reduced IL-1-induced PAI-1 expression in 4G/4G HUVEC compared with untreated cultures (177.5% +/- 24.5% vs. 257.9% +/- 39.0%, P < 0.05). Pravastatin also attenuated the amount of secreted PAI-1 by 4G/4G HUVEC after IL-1 stimulation (5020.6 +/- 165.7 ng mL(-1) vs. 4261.1 +/- 309.8 ng mL(-1), P < 0.05). This effect was prevented by coincubation with mevalonate, indicating a dependence on HMG-CoA reductase inhibition. CONCLUSIONS: The endothelial 4G/5G PAI-1 genotype influences the PAI-1 response to IL-1alpha and the modulatory effect of pravastatin. As increased PAI-1 levels have been linked to cardiovascular disease the observed endothelial modulation by pravastatin may have potential clinical implications

Validation of plasma fibrinogen as a marker of carotid atherosclerosis in subjects free of clinical cardiovascular disease

BACKGROUND AND OBJECTIVES: Fibrinogen has been found to be an independent risk factor for cardiovascular disease. The aim of this study was to validate the measurement of plasma fibrinogen as a marker of subclinical atherosclerosis in a series of asymptomatic subjects (n=519, median age 55.5 years, 80% men). DESIGN AND METHODS: All individuals had a complete clinical examination, lipid profile (cholesterol and its high and low density lipoprotein fractions and triglycerides), global vascular risk assessment (PROCAM), and B-mode ultrasonography of the carotid arteries to determine the intima-media thickness (IMT) and the presence of atheroma plaques. C-reactive protein (CRP), and von Willebrand factor (vWF) were also measured in all subjects as markers of inflammation/endothelial damage. RESULTS: In the univariate model, a positive relationship was found between plasma fibrinogen concentration and carotid IMT (p<0.001). Fibrinogen concentration also correlated positively with age (p<0.001), systolic blood pressure (p<0.001), smoking (p<0.05), diabetes (p<0.05), PROCAM (p<0.001), CRP and vWF (p<0.001). In the multivariate analysis, the association of fibrinogen with carotid IMT remained significant (p=0.008) after adjustment for all parameters analyzed. INTERPRETATION AND CONCLUSIONS: In a population sample of adults without clinically overt atherosclerotic disease, elevated fibrinogen levels was related to carotid IMT independently of a wide range of important confounding variables. Plasma fibrinogen may represent a systemic marker of carotid atherosclerosis

STATISTICAL ANALYSIS OF THE EFFECTS OF MIXING POTATO VARIETIES ON LATE BLIGHT

A field study in two regions of Peru was conducted to determine how host-diversity effects on potato late blight varied geographically. Foliar disease severity was evaluated separately for the potato varieties in mixtures as well as in the single-variety plots. The TAUDPC (truncated area under the disease progress curve) and RMR (relative mixture response) for each site were analyzed separately using SAS mixed effects model procedures. While there was little difference between the sites in the 1997-1998 season, host-diversity effects were generally greater near Huancayo than near Cajamarca in the 1998-1999 season. Estimates of host-diversity effects from studies in Oregon and Ecuador were also compared with results for Peru. Host-diversity effects for reduced disease were generally greater for sites where we predicted lower levels of outside inoculum

Protective effect of the G-765C COX-2 polymorphism on subclinical atherosclerosis and inflammatory markers in asymptomatic subjects with cardiovascular risk factors

BACKGROUND: Cyclooxygenase (COX)-2, a key regulatory enzyme in prostanoid synthesis, plays an important role in inflammatory processes. The -765G>C COX-2 polymorphism has been associated with lower promoter activity in vitro and reduced levels of C-reactive protein (CRP) in atherosclerotic carriers of the C allele. However, its pathophysiological relevance in vivo has not been fully elucidated. METHODS AND RESULTS: We assessed the -765G>C polymorphism and COX-2 expression in 220 asymptomatic subjects free of cardiovascular disease, in relation to global vascular risk, carotid intima-media thickness (IMT), and inflammatory markers (fibrinogen, C-reactive protein [CRP], von Willebrand factor [vWF] and interleukin-6 [IL-6]). Genotype frequencies were: CC (7.7%), CG (34.5%), GG (57.7%). Among hypercholesterolemic subjects (n=140), C allele carriers had lower COX-2 expression (p<0.05), reduced carotid IMT (p<0.01) and diminished levels of inflammatory markers CRP, vWF and IL-6 (p<0.05), as compared to GG homozygous subjects. The association between carotid IMT and COX-2 polymorphism remained significant after adjusting for cardiovascular risk factors and inflammatory markers (p=0.008). CONCLUSIONS: In asymptomatic hypercholesterolemic subjects the C allele of -765G>C COX-2 polymorphism was associated with lower COX-2 expression, and reduced subclinical atherosclerosis and systemic inflammation compared with GG homozygous, thus conferring atherosclerosis protection in this cardiovascular risk population

Antioxidant vitamins increase the collagen content and reduce MMP-1 in a porcine model of atherosclerosis: implications for plaque stabilization

Degradation of extracellular matrix, particularly interstitial collagen, promotes plaque instability and contributes to restenosis after vascular injury. We have explored the effects of vitamins C and E on the collagen content and metalloproteinase-1 (MMP-1) expression after angioplasty in hypercholesterolemic pigs. Iliac angioplasty was performed on 18 minipigs divided into three diet groups: a normal-cholesterol (NC), a high-cholesterol (HC) and a high-cholesterol plus vitamins C+E (HCV). Four weeks later, after sacrifice, the vascular collagen content and MMP-1 protein expression, along with the plasma caseinolytic activity and lipid peroxidation, were measured. MMP-1 was also determined in arterial rings stimulated with native low-density lipoproteins (LDL) isolated from experimental groups. Cholesterol-rich diet augmented plasma lipid peroxidation (P<0.05), reduced the collagen content and increased vascular MMP-1 expression after injury (P<0.05). Enhanced caseinolytic activity (identified as MMP-1) was also observed in HC plasma samples and in supernatants from arterial rings incubated with HC-LDL. Vitamins C and E markedly increased neointimal collagen content (P<0.01), reduced the hypercholesterolemia-induced changes in vascular MMP-1 (P<0.05) and diminished plasma and ex vivo caseinolytic activity. Vitamins C and E may help stabilize atherosclerotic plaque after angioplasty and favor vascular remodeling by increasing collagen content and reducing vascular MMP-1 expression in porcine hypercholesterolemia

Different expression of MMPs/TIMP-1 in human atherosclerotic lesions. Relation to plaque features and vascular bed

BACKGROUND: Proteolytic imbalance might determine arterial remodeling and plaque destabilization in atherosclerotic vessels. The aim of this study was to examine differences in the patterns of metalloproteinases (MMPs) and MMP inhibitor (TIMP-1) expression in advanced human atheromas, both in relation to the plaque features and the vascular bed involved. METHODS AND RESULTS: Immunohistochemistry for MMP-1, -3, -9 and TIMP-1 as well as the collagen content were measured in vascular sections from patients undergoing peripheral revascularization (carotid n=11, femoral n=23) and aorto-coronary bypass surgery (mammary arteries n=20, as controls). Increased expression of all MMPs was detected in atherosclerotic as compared with control sections (P<0.01). Aneurysmal plaques showed a significant increase of MMP-1 and-3 and a reduction in total collagen (P<0.05) in relation to occlusive lesions. Calcification areas in atherosclerotic plaques were consistently associated with increased TIMP-1 expression (P<0.01). Finally, MMP-9 expression was higher in occlusive lesions from carotid than femoral arteries (P<0.01). CONCLUSIONS: Aneurysm lesions expressed higher MMP-1 and-3 expression than occlusive plaques, and MMP-9 was mainly detected in carotid as compared with femoral arteries. TIMP-1 was associated with arterial calcification. These differences in the MMPs/TIMP-1 expression might determine the evolution of advanced atherosclerotic plaques and contribute to its vulnerability