Dysfunctional high-density lipoproteins in type 2 diabetes mellitus: Molecular mechanisms and therapeutic implications

High density lipoproteins (HDLs) are commonly known for their anti-atherogenic properties that include functions such as the promotion of cholesterol efflux and reverse cholesterol transport, as well as antioxidant and anti-inflammatory activities. However, because of some chronic inflammatory diseases, such as type 2 diabetes mellitus (T2DM), significant changes occur in HDLs in terms of both structure and composition. These alterations lead to the loss of HDLs’ physiological functions, to transformation into dysfunctional lipoproteins, and to increased risk of cardiovascular disease (CVD). In this review, we describe the main HDL structural/functional alterations observed in T2DM and the molecular mechanisms involved in these T2DM-derived modifications. Finally, the main available therapeutic interventions targeting HDL in diabetes are discussed

Impact of dietary lipids on the reverse cholesterol transport: What we learned from animal studies

Reverse cholesterol transport (RCT) is a physiological mechanism protecting cells from an excessive accumulation of cholesterol. When this process begins in vascular macrophages, it acquires antiatherogenic properties, as has been widely demonstrated in animal models. Dietary lipids, despite representing a fundamental source of energy and exerting multiple biological functions, may induce detrimental effects on cardiovascular health. In the present review we summarize the current knowledge on the mechanisms of action of the most relevant classes of dietary lipids, such as fatty acids, sterols and liposoluble vitamins, with effects on different steps of RCT. We also provide a critical analysis of data obtained from experimental models which can serve as a valuable tool to clarify the effects of dietary lipids on cardiovascular disease

Similarity Measures For Incomplete Database Instances

The problem of comparing database instances with incompleteness is prevalent in applications such as analyzing how a dataset has evolved over time (e.g., data versioning), evaluating data cleaning solutions (e.g., compare an instance produced by a data repair algorithm against a gold standard), or comparing solutions generated by data exchange systems (e.g., universal vs core solutions). In this work, we propose a framework for computing similarity of instances with labeled nulls, even of those without primary keys. As a side-effect, the similarity score computation returns a mapping between the instances’ tuples, which explains the score. We demonstrate that computing the similarity of two incomplete instances is NP-hard in the instance size in general. To be able to compare instances of realistic size, we present an approximate PTIME algorithm for instance comparison. Experimental results demonstrate that the approximate algorithm is up to three orders of magnitude faster than an exact algorithm for the computation of the similarity score, while the difference between approximate and exact scores is always smaller than 1%

Experimental studies on the SPS electron cloud

One of the most important limitations in the performances of the CERN-SPS is presently the Electron Cloud Instability (ECI). Hence, defining its dependence on energy with confidence is an indispensable asset to direct the efforts for all the upgrade studies. Macroparticle simulations carried out with the HEADTAIL code have shown that the ECI mechanism is subtle and the scaling laws valid for the Transverse Mode Coupling Instability cannot be applied to it . The reason lies in the fact that the electron dynamics, while a bunch is going through an electron cloud, is heavily affected by the transverse beam size. In fact, transversely smaller beams can enhance the electron pinch and lower the intensity threshold for the bunch to be unstable. Hence, higher energy beams, though more rigid, can be more unstable due to their smaller transverse size (with constant transverse normalized emittance). During the 2007 run a measurement campaign has been carried out at the CERN-SPS to prove experimentally the outcomes of macroparticle simulations

Dependence of the Electron-Cloud Instability on the Beam Energy

The electron cloud (EC) can be formed in the beam pipe of a circular accelerator if the secondary emission yield (SEY) of the inner surface is larger than 1, and it can detrimentally affect the circulating beam. Understanding the underlying physics and defining the scaling laws of this effect is indispensable to steer the upgrade plans of the existing machines and the design of new ones. The single bunch EC instability (ECI) is shown to be strongly affected by the transverse beam size. Transversely, smaller beams going through an electron cloud generate higher electron peak densities and lower the intensity threshold to make the beam unstable. In particular, since higher energy beams have smaller transverse sizes (for equal normalized transverse emittances), the scaling of the ECI threshold with the beam energy turns out to be surprisingly unfavorable

Experimental Study of the Electron Cloud Instability at the CERN SPS

The electron cloud instability limits the performance of many existing proton and positron rings. A simulation study carried out with the HEADTAIL code revealed that the threshold for its onset decreases with increasing beam energy, if the 6D emittance of the bunch is kept constant and the longitudinal matching to the bucket is preserved. Experiments have been carried out at the CERN-SPS to study the dependence of the vertical electron cloud instability on the energy and on the beam size. The reduction of the physical transverse emittance as a function of energy is considered in fact to be the main reason for the unusual dependence of this instability on energy

Transverse Mode-Coupling Instability in the CERN SPS: Comparing Moses Analytical Calculations and Headtail Simulations with experiments in the SPS

Since 2003, single bunches of protons with high intensity (1.2e11 protons) and low longitudinal emittance (0.2 eVs) have been observed to suffer from heavy losses in less than one synchrotron period after injection at 26 GeV/c in the CERN Super Proton Synchrotron (SPS) when the vertical chromaticity is corrected. Understanding the mechanisms underlying this instability is crucial to assess the feasibility of an anticipated upgrade of the SPS, which requires bunches of 4e11 protons. Analytical calculations from MOSES and macroparticle tracking simulations using HEADTAIL with an SPS transverse impedance modelled as a broadband resonator had already qualitatively and quantitatively agreed in predicting the intensity threshold of a fast instability. A sensitive frequency analysis of the HEADTAIL simulations output was performed using SUSSIX, and revealed the fine structure of the mode spectrum of the bunch coherent motion. A coupling between the azimuthal modes "-2"and "-3" was clearly observed to be the reason for this fast instability. The aim of this contribution is to compare the HEADTAIL simulations with dedicated measurements performed in the SPS in 2007

Measurements of the LHC longitudinal resistive impedance with beam

The resistive part of the longitudinal impedance contributes to the heat deposition on different elements in the LHC ring including the beam screens, where it has to be absorbed by the cryogenic system and can be a practical limitation for the maximum beam intensity. In this paper, we present the first measurements of the LHC longitudinal resistive impedance with beam, done through synchronous phase shift measurements duringMachine Development sessions in 2012. Synchronous phase shift is measured for different bunch intensities and lengths using the high-precision LHC Beam Phase Module and then data are post-processed to further increase the accuracy. The dependence of the energy loss per particle on bunch length is then obtained and compared with the expected values found using the LHC impedance model