Duality and o-O structure in non reflexive banach spaces

Let E be a Banach space with a supremum type norm induced by a collection of functionals L ⊂ X∗where X is a reflexive Banach space. Familiar spaces of this type are BMO, BV, C0,α(0 < α < 1), Lq,∞, for q > 1. For most of these spaces E, the predual E∗ exists and can be defined by atomic decomposition of its elements. Another typical result, when it is possible to define a rich vanishing subspace E0⊂ E is the "two star theorem ", namely (E0)∗ = E∗. This fails for E = BV and E =C0,1= Lip

Orlicz regularity of the gradient of solutions to quasilinear elliptic equations in the plane

Given a planar domain Omega, we study the Dirichlet problem {-divA(x, del v) = f in Omega, v = 0 on partial derivative Omega, where the higher-order term is a quasilinear elliptic operator, and f belongs to the Zygmund space L(log L)delta(log log log L)(beta/2) (Omega) with beta >= 0 and delta >= 1/2. We prove that the gradient of the variational solution v is an element of W-0(1,2) (Omega) belongs to the space L-2(log L)(2 delta-1)(log log log L)(beta)(Omega)

Fuzzy logic on quantum annealers

Quantum computation is going to revolutionize the world of computing by enabling the design of massive parallel algorithms that solve hard problems in an efficient way, thanks to the exploitation of quantum mechanics effects, such as superposition, entanglement and interference. These computational improvements could strongly influence the way how fuzzy systems are designed and used in contexts, such as big data, where computational efficiency represents a non-negligible constraint to be taken into account. In order to pave the way towards this innovative scenario, this paper introduces a novel representation of fuzzy sets and operators based on Quadratic Unconstrained Binary Optimization (QUBO) problems, so as to enable the implementation of fuzzy inference engines on a type of quantum computers known as quantum annealers

Biophysical and biochemical characterization of a liposarcoma-derived recombinant MnSOD protein acting as an anticancer agent

A recombinant MnSOD (rMnSOD) synthesized by specific cDNA clones derived from a liposarcoma cell line was shown to have the same sequence as the wild-type MnSOD expressed in the human myeloid leukaemia cell line U937, except for the presence of the leader peptide at the N-terminus. These results were fully confirmed by the molecular mass of rMnSOD as evaluated by ES/MS analysis (26662.7 Da) and the nucleotide sequence of the MnSOD cDNA. The role of the leader peptide in rMnSOD was investigated using a fluorescent and/or 68Gallium-labelled synthetic peptide. The labelled peptide permeated MCF-7 cells and uptake could be inhibited in the presence of an excess of oestrogen. In vivo it was taken up by the tumour, suggesting that the molecule can be used for both therapy and diagnosis. The in vitro and in vivo pharmacology tests confirmed that rMnSOD is only oncotoxic for tumour cells expressing oestrogen receptors. Pharmacokinetic studies in animals performed with 125I- and 131I-labelled proteins confirmed that, when administered systemically, rMnSOD selectively reached the tumour, where its presence was unambiguously demonstrated by scintigraphic and PET scans. PCR analysis revealed that Bax gene expression was increased and the Bcl2 gene was down regulated in MCF7 cells treated with rMnSOD, which suggests that the protein induces a pro-apoptotic mechanism

Fuzzy inference on quantum annealers

Quantum computers can potentially perform certain types of optimisation problems much more efficiently than classical computers, making them a promising tool for solving complex fuzzy logic problems. In two recent developments, based on solving Quadratic Unconstrained Binary Optimization (QUBO) problems on a type of quantum computers known as quantum annealers, we have introduced novel representations of a) fuzzy sets; b) implementations of some basic fuzzy logic operators (union, intersection, alpha-cut and maximum) and; c) the centroid defuzzification. In this paper, the previous works are further extended by presenting an implementation of Mamdani inference on the quantum annealer machines. We first present how the fuzzy rules can be formulated for such an implementation, then we present how to cascade different quantum-fuzzy operators in order to implement the quantum-fuzzy inference, and finally, a sample implementation of the inference on a real quantum computer is demonstrated. Having the main components of a rule-based fuzzy logic system implemented on quantum computers, this paper provides an integrated solution for implementing a whole fuzzy rule-based system on quantum computers

Ion channels in the pathogenesis of endometriosis: A cutting-edge point of view

Background: Ion channels play a crucial role in many physiological processes. Several subtypes are expressed in the endometrium. Endometriosis is strictly correlated to estrogens and it is evident that expression and functionality of different ion channels are estrogen-dependent, fluctuating between the menstrual phases. However, their relationship with endometriosis is still unclear. Objective: To summarize the available literature data about the role of ion channels in the etiopathogenesis of endometriosis. Methods: A search on PubMed and Medline databases was performed from inception to November 2019. Results: Cystic fibrosis transmembrane conductance regulator (CFTR), transient receptor potentials (TRPs), aquaporins (AQPs), and chloride channel (ClC)-3 expression and activity were analyzed. CFTR expression changed during the menstrual phases and was enhanced in endometriosis samples; its overexpression promoted endometrial cell proliferation, migration, and invasion throughout nuclear factor kappa-light-chain-enhancer of activated B cells-urokinase plasminogen activator receptor (NFκB-uPAR) signaling pathway. No connection between TRPs and the pathogenesis of endometriosis was found. AQP5 activity was estrogen-increased and, through phosphatidylinositol-3-kinase and protein kinase B (PI3K/AKT), helped in vivo implantation of ectopic endometrium. In vitro, AQP9 participated in extracellular signal-regulated kinases/p38 mitogen-activated protein kinase (ERK/p38 MAPK) pathway and helped migration and invasion stimulating matrix metalloproteinase (MMP)2 and MMP9. ClC-3 was also overexpressed in ectopic endometrium and upregulated MMP9. Conclusion: Available evidence suggests a pivotal role of CFTR, AQPs, and ClC-3 in endometriosis etiopathogenesis. However, data obtained are not sufficient to establish a direct role of ion channels in the etiology of the disease. Further studies are needed to clarify this relationship

Left ventricular dysfunction in heart failure with preserved ejection fraction-molecular mechanisms and impact on right ventricular function

The current classification of heart failure (HF) based on left ventricular (LV) ejection fraction (EF) identifies a large group of patients with preserved ejection fraction (HFpEF) with significant morbidity and mortality but without prognostic benefit from current HF therapy. Co-morbidities and conditions such as arterial hypertension, diabetes mellitus, chronic kidney disease, adiposity and aging shape the clinical phenotype and contribute to mortality. LV diastolic dysfunction and LV structural remodeling are hallmarks of HFpEF, and are linked to remodeling of the cardiomyocyte and extracellular matrix. Pulmonary hypertension (PH) and right ventricular dysfunction (RVD) are particularly common in HFpEF, and mortality is up to 10-fold higher in HFpEF patients with vs. without RV dysfunction. Here, we review alterations in cardiomyocyte function (i.e., ion homeostasis, sarcomere function and cellular metabolism) associated with diastolic dysfunction and summarize the main underlying cellular pathways. The contribution and interaction of systemic and regional upstream signaling such as chronic inflammation, neurohumoral activation, and NO-cGMP-related pathways are outlined in detail, and their diagnostic and therapeutic potential is discussed in the context of preclinical and clinical studies. In addition, we summarize prevalence and pathomechanisms of RV dysfunction in the context of HFpEF and discuss mechanisms connecting LV and RV dysfunction in HFpEF. Dissecting the molecular mechanisms of LV and RV dysfunction in HFpEF may provide a basis for an improved classification of HFpEF and for therapeutic approaches tailored to the molecular phenotype

Use of statins in lower extremity artery disease: a review

BACKGROUND: Lower extremity artery disease (LE-PAD) is one of the most common manifestations of atherosclerosis, particularly in elderly patients, and it is related to a high cardiovascular risk. DESCRIPTION: It is well established that statin therapy is characterized by crucial benefits on cardiovascular system by limiting atherosclerotic progression and reducing cardiovascular events and mortality. A growing body of evidence support efficacy of statins in LE-PAD due to the ability of both reducing cardiovascular risk and improving walking distance and, hence, quality of life. Consequently, statin therapy should be considered in all LE-PAD patients and new LDL-cholesterol targets should be reached. CONCLUSIONS: Our opinion is that statin therapy remains still underutilized or with inadequate dosage, so therapy of LE-PAD patients should be improved to obtain all the demonstrated benefits of statin

The impact of cluster connectedness on firm innovation: R&D effort and outcomes in the textile industry

This is an Author's Accepted Manuscript of an article published in "The impact of cluster connectedness on firm innovation: R&D effort and outcomes in the textile industry" version of the article as published in the Entrepreneurship and Regional Development, 2012 september,[copyright Taylor & Francis], available online at: http://www.tandfonline.com/10.1080/08985626.2012.710260"[EN] Recent research into the clustering effect on firms has moved away from a simplistic view to a more complex approach. More realistic and complex causal relationships are now considered when analysing these territorial networks. Specifically, this paper attempts to analyse how cluster connect- edness moderates the relationship of a firm's innovation effort and the results obtained from this effort. We want to question the commonly accepted direct and positive impact of R&D effort, and moreover, we suggest the existence of a saturation effect and that the level of cluster's inter-connectedness in the cluster moderates this effect. We have developed our empirical study focusing on the Spanish textile industrial cluster. This is a complex manufacturing industry that uses relatively low-technology manufacturing and R&D. Our findings suggest that the degree to which a firm is involved with, or connected to, other firms in the cluster can moderate the effect of the R&D effort on its innovation results. More generally, we aim to contribute to the discussion on the degree to which firms should be involved in the cluster network in order to operate efficiently and gain the maximum competitive advantages. Our findings have implications both in recent cluster and network literature as well for institutional policy.Molina Morales, FX.; Expósito Langa, M. (2012). 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Impairment of the adrenergic reserve associated with exercise intolerance in a murine model of heart failure with preserved ejection fraction

This project is funded by grants from the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation—SFB 1470—A01 to FRH and PA and A02 to GGS) and from the DZHK (German Centre for Cardiovascular Research to GGS). CUO is additionally funded by the DFG (OE 688/4-1).Aim Exercise intolerance is the central symptom in patients with heart failure with preserved ejection fraction. In the present study, we investigated the adrenergic reserve both in vivo and in cardiomyocytes of a murine cardiometabolic HFpEF model. Methods 12-week-old male C57BL/6J mice were fed regular chow (control) or a high-fat diet and L-NAME (HFpEF) for 15 weeks. At 27 weeks, we performed (stress) echocardiography and exercise testing and measured the adrenergic reserve and its modulation by nitric oxide and reactive oxygen species in left ventricular cardiomyocytes. Results HFpEF mice (preserved left ventricular ejection fraction, increased E/e', pulmonary congestion [wet lung weight/TL]) exhibited reduced exercise capacity and a reduction of stroke volume and cardiac output with adrenergic stress. In ventricular cardiomyocytes isolated from HFpEF mice, sarcomere shortening had a higher amplitude and faster relaxation compared to control animals. Increased shortening was caused by a shift of myofilament calcium sensitivity. With addition of isoproterenol, there were no differences in sarcomere function between HFpEF and control mice. This resulted in a reduced inotropic and lusitropic reserve in HFpEF cardiomyocytes. Preincubation with inhibitors of nitric oxide synthases or glutathione partially restored the adrenergic reserve in cardiomyocytes in HFpEF. Conclusion In this murine HFpEF model, the cardiac output reserve on adrenergic stimulation is impaired. In ventricular cardiomyocytes, we found a congruent loss of the adrenergic inotropic and lusitropic reserve. This was caused by increased contractility and faster relaxation at rest, partially mediated by nitro-oxidative signaling.Peer reviewe