Alterations of Hyaluronan Metabolism in Acute Coronary Syndrome: Implications for Plaque Erosion

Background: Superficial erosion currently causes at least one-third of acute coronary syndromes (ACS), and its incidence is increasing. Yet, the underlying mechanisms in humans are still largely unknown. Objectives: The authors sought to assess the role of hyaluronan (HA) metabolism in ACS. Methods: Peripheral blood mononuclear cells were collected from ACS (n = 66), stable angina (SA) (n = 55), and control (CTRL) patients (n = 45). The authors evaluated: 1) gene expression of hyaluronidase 2 (HYAL2) (enzyme degrading high-molecular-weight HA to its proinflammatory 20-kDa isoform) and of CD44v1, CD44v4, and CD44v6 splicing variants of HA receptor; and 2) HYAL2 and CD44 protein expression. Moreover, they compared HYAL2 and CD44 gene expression in ACS patients with plaque erosion (intact fibrous cap and thrombus) and in ACS patients with plaque rupture, identified by optical coherence tomography analysis. Results: Gene expression of HYAL2, CD44v1, and CD44v6 were significantly higher in ACS as compared with SA (p = 0.003, p < 0.001, and p = 0.033, respectively) and CTRL subjects (p < 0.001, p < 0.001, and p = 0.009, respectively). HYAL2 protein expression was significantly higher in ACS than in SA (p = 0.017) and CTRL (p = 0.032), whereas no differences were found in CD44 protein expression. HYAL2 and CD44v6 gene expression was significantly higher in patients with plaque erosion than in those with plaque rupture (p = 0.015 and p = 0.029, respectively). Conclusions: HYAL2 and CD44v6 splicing variants seem to play an important role in ACS, in particular when associated with plaque erosion. After further validation, HYAL2 might represent a potentially useful biomarker for the noninvasive identification of this mechanism of coronary instability

Multiple options noisy voter model: application to European elections

A thesis submitted in fulfillment of the requirements for the degree of Master in Physics of Complex Systems in the IFISC-CSIC-UIB.In the following master thesis we are going to present a noisy voter model based on social influence and recurrent mobility. The state of the agents of the model is described through a ternary option a = f1; 0; 1g, and interactions between elements holding opposite opinion are not permitted (-1 and 1). The aim is to observe if our model is capable to reproduce the time evoution of real general elections, and the Spanish political context is chosen for a confrontation: IU, PSOE, and PP will correspond respectively to the options (-1,0,1) of our model. During the time evolution the agents will move repeatedly between the municipality in which they live and the municipality in which they work (commuting network), and at each time all agents present in the same municipality will be considered reciprocally neighbours. The commuting network is constructed according with the spanish census data, and electoral results of year 2000 are used as initial state of the whole system. A preliminar statistical analysis of real elections show us that the three options considered can be divided into majoritarian (PSOE and PP) and minoritarian (IU).The original version of the model will not be able to capture the statistical features of real elections data, giving rise to stationary states in which the three options result to be statistically equivalent (on the contrary of what observed in real election data). However, a simple modification of the same model (well sustained theoretically) will permit us to reproduce most of the aspects of time evolution showed by real data, as the stationarity of the vote sharing standard deviations , the conservation of the shape of the vote sharing distrutions, and the time evolution of the average vote sharing of the minoritarian option, which in this modification keep staying minoritarian.Peer reviewe

Multiple options noisy voter model: application to European elections

[eng] In the following master thesis we are going to present a noisy voter model based on social influence and recurrent mobility. The state of the agents of the model is described through a ternary option a = {−1, 0, 1}, and interactions between elements holding opposite opinion are not permitted (-1 and 1). The aim is to observe if our model is capable to reproduce the time evoution of real general elections, and the Spanish political context is chosen for a confrontation: IU, PSOE, and PP will correspond respectively to the options (-1,0,1) of our model. During the time evolution the agents will move repeatedly between the municipality in which they live and the municipality in which they work (commuting network), and at each time all agents present in the same municipality will be considered reciprocally neighbours. The commuting network is constructed according with the spanish census data, and electoral results of year 2000 are used as initial state of the whole system. A preliminar statistical analysis of real elections show us that the three options considered can be divided into majoritarian (PSOE and PP) and minoritarian (IU).The original version of the model will not be able to capture the statistical features of real elections data, giving rise to stationary states in which the three options result to be statistically equivalent (on the contrary of what observed in real election data). However, a simple modification of the same model (well sustained theoretically) will permit us to reproduce most of the aspects of time evolution showed by real data, as the stationarity of the vote sharing standard deviations , the conservation of the shape of the vote sharing distrutions, and the time evolution of the average vote sharing of the minoritarian option, which in this modification keep staying minoritarian

Mechanochemical synthesis of Cu(i)-N-heterocyclic carbene complexes

We report a general, operationally simple and scalable mechanochemical method for the synthesis of [Cu(Cl)(NHC)] complexes. This solid-state and solvent-less methodology was shown to be applicable to a wide range of NHC ligand precursors, allowing access to complexes of the type [Cu(Cl)(NHC)] under aerobic conditions and with minimised environmental impact

General mechanochemical synthetic protocol to late transition metal-NHC (N-Heterocyclic Carbene) complexes

A user-friendly and highly efficient mechanochemical strategy for the synthesis of a number of well-defined, catalytically relevant N-heterocyclic carbene-metal complexes under aerobic conditions is reported. This protocol proceeds in good to excellent yields and limits solvent usage to the purification step, which can be carried out, after judicious selection, using minimal amounts of environmentally benign solvents

Synthetic access to aromatic alpha-haloketones

alpha-Haloketones play an essential role in the synthesis of complex N-, S-, O-heterocycles; of which some exhibit a remarkable biological activity. Research further illustrated that alpha-bromo-, alpha-chloro-, and alpha-iodoketones are key precursors for blockbuster pharmacological compounds. Over the past twenty years, substantial advances have been made in the synthesis of these industrially relevant building blocks. Efforts have focused on rendering the synthetic protocols greener, more effective and versatile. In this survey, we summarised and thoroughly evaluated the progress of the field, established in the past two decades, in terms of generality, efficacy and sustainability

The 'weak base route' leading to transition metal-N-heterocyclic carbene complexes

N-Heterocyclic carbenes (NHCs) are nowadays ubiquitous in organometallic chemistry and catalysis. Recently, a synthetic method which makes use of weak bases and desirable solvents has emerged as a simple, widely applicable and cost-effective pathway to well defined M-NHC complexes. Herein, recent studies devoted to the weak base approach are examined in detail, in order to showcase the simplicity, scope and variations of the method with regards to the azolium salts, bases and the metal sources, as well as the reaction conditions used. Mechanistic investigations are presented, illustrating the formation of intermediates which are air and moisture stable, prior to the metallation step. Finally, the importance, limitations and future prospects of the weak base route are discussed

Continuous flow synthesis of metal-NHC complexes

The use of weak bases and mild conditions is currently the most sustainable and attractive synthetic approach for the preparation of late-transition metal complexes, some of which are widely used in catalysis, medicinal chemistry and materials science. Herein, the use of cuprate, aurate or palladate species for a continuous flow preparation of Cu-I, Au-I and Pd-II-NHC complexes is reported. All reactions examined proceed under extremely mild conditions and make use of technical grade acetone as solvent. The scalability of the process was exemplified in a multigram-scale synthesis of [Cu(IPr)Cl]

NHC complexes in flow (NHC = N‐heterocyclic carbene)

N-Heterocyclic carbenes (NHCs) have proven themselves to be a popular and versatile ligand family for the synthesis of organometallic compounds. With interesting use cases in catalysis, medicinal chemistry and material sciences, the widespread use of this novel class of ligands has been a driving force for the development of a sustainable, efficient, and user-friendly route towards their synthesis. So far, the most commonly used synthetic strategy leading to NHC complexes, has involved the generation of free NHC by deprotonation of the corresponding azolium salt with a strong base (e.g.NaH, KOtBu) and subsequent coordination to a metal or chalcogen. However, this approach presents several drawbacks such as the need for strictly anhydrous conditions and incompatibility with the use of metal precursors which are sensitive to strong bases. Alternatively, the use of weak bases and mild conditions is currently the most sustainable and attractive synthetic approach for the preparation of Late-Transition Metal-NHC complexes. In our recent pieces of work, we have translated the latter method to a continuous flow system. This technology provides superior mass and heat transfer rates and allows for the use of small volumes of reagents and in turn enables easy and safe handling of hazardous reagents. Using this setup, complete conversion of cuprate, aurate or palladate species was achieved, yielding the targeted Cu(I), Au(I) and Pd(II)-NHC complexes in excellent yield, without the need for further purification. The scalability of the process was exemplified in the multigram-scale synthesis of [Cu(IPr)Cl]. Additionally, this simplistic reactor design also proved capable of synthesizing Sulfur‐ and Selenium‐NHC Compounds in similarly mild conditions, as well as the further arylation of the metal centre in a telescoped setup. All reactions examined proceed under extremely mild conditions and make use of technical grade acetone as solvent