Evolving targets for lipid-modifying therapy

Published online: August 29, 2014The pathogenesis and progression of atherosclerosis are integrally connected to the concentration and function of lipoproteins in various classes. This review examines existing and emerging approaches to modify low-density lipoprotein and lipoprotein (a), triglyceride-rich lipoproteins, and high-density lipoproteins, emphasizing approaches that have progressed to clinical evaluation. Targeting of nuclear receptors and phospholipases is also discussed.Rose Q Do, Stephen J Nicholls and Gregory G Schwart

Forward Neutral Pion Transverse Single Spin Asymmetries in p+p Collisions at \sqrt{s}=200 GeV

We report precision measurements of the Feynman-x dependence, and first measurements of the transverse momentum dependence, of transverse single spin asymmetries for the production of \pi^0 mesons from polarized proton collisions at \sqrt{s}=200 GeV. The x_F dependence of the results is in fair agreement with perturbative QCD model calculations that identify orbital motion of quarks and gluons within the proton as the origin of the spin effects. Results for the p_T dependence at fixed x_F are not consistent with pQCD-based calculations.Comment: 6 pages, 4 figure

Longitudinal Spin Transfer to Λ\Lambda and Λˉ\bar{\Lambda} Hyperons in Polarized Proton-Proton Collisions at s\sqrt{s} = 200 GeV

The longitudinal spin transfer, $D_{LL}$, from high energy polarized protons to $\Lambda$ and $\bar{\Lambda}$ hyperons has been measured for the first time in proton-proton collisions at $\sqrt{s} = 200 \mathrm{GeV}$ with the STAR detector at RHIC. The measurements cover pseudorapidity, $\eta$, in the range $|\eta| < 1.2$ and transverse momenta, $p_\mathrm{T}$, up to $4 \mathrm{GeV}/c$. The longitudinal spin transfer is found to be $D_{LL}= -0.03\pm 0.13(\mathrm{stat}) \pm 0.04(\mathrm{syst})$ for inclusive $\Lambda$ and $D_{LL} = -0.12 \pm 0.08(\mathrm{stat}) \pm 0.03(\mathrm{syst})$ for inclusive $\bar{\Lambda}$ hyperons with $= 0.5$ and $= 3.7 \mathrm{GeV}/c$. The dependence on $\eta$ and $p_\mathrm{T}$ is presented.Comment: 5 pages, 4 figure

Growth of Long Range Forward-Backward Multiplicity Correlations with Centrality in Au+Au Collisions at sNN\sqrt{s_{NN}} = 200 GeV

Forward-backward multiplicity correlation strengths have been measured with the STAR detector for Au+Au and $\textit{p+p}$ collisions at $\sqrt{s_{NN}}$ = 200 GeV. Strong short and long range correlations (LRC) are seen in central Au+Au collisions. The magnitude of these correlations decrease with decreasing centrality until only short range correlations are observed in peripheral Au+Au collisions. Both the Dual Parton Model (DPM) and the Color Glass Condensate (CGC) predict the existence of the long range correlations. In the DPM the fluctuation in the number of elementary (parton) inelastic collisions produces the LRC. In the CGC longitudinal color flux tubes generate the LRC. The data is in qualitative agreement with the predictions from the DPM and indicates the presence of multiple parton interactions.Comment: 6 pages, 3 figures The abstract has been slightly modifie

K/pi Fluctuations at Relativistic Energies

We report results for $K/\pi$ fluctuations from Au+Au collisions at $\sqrt{s_{NN}}$ = 19.6, 62.4, 130, and 200 GeV using the STAR detector at the Relativistic Heavy Ion Collider. Our results for $K/\pi$ fluctuations in central collisions show little dependence on the incident energies studied and are on the same order as results observed by NA49 at the Super Proton Synchrotron in central Pb+Pb collisions at $\sqrt{s_{NN}}$ = 12.3 and 17.3 GeV. We also report results for the collision centrality dependence of $K/\pi$ fluctuations as well as results for $K^{+}/\pi^{+}$, $K^{-}/\pi^{-}$, $K^{+}/\pi^{-}$, and $K^{-}/\pi^{+}$ fluctuations. We observe that the $K/\pi$ fluctuations scale with the multiplicity density, $dN/d\eta$, rather than the number of participating nucleons.Comment: 6 pages, 4 figure

Sustained Domestic Vector Exposure Is Associated With Increased Chagas Cardiomyopathy Risk but Decreased Parasitemia and Congenital Transmission Risk Among Young Women in Bolivia

Vector exposure showed a direct association with Chagas cardiomyopathy, but an inverse relationship with maternal parasitemia and congenital transmission. We hypothesize that repeated antigen exposure maintains an inflammatory response, increasing cardiomyopathy, but this upregulation improves control of parasitemia during pregnanc

Temporal Pattern of ICAM-I Mediated Regulatory T Cell Recruitment to Sites of Inflammation in Adoptive Transfer Model of Multiple Sclerosis

Migration of immune cells to the target organ plays a key role in autoimmune disorders like multiple sclerosis (MS). However, the exact underlying mechanisms of this active process during autoimmune lesion pathogenesis remain elusive. To test if pro-inflammatory and regulatory T cells migrate via a similar molecular mechanism, we analyzed the expression of different adhesion molecules, as well as the composition of infiltrating T cells in an in vivo model of MS, adoptive transfer experimental autoimmune encephalomyelitis in rats. We found that the upregulation of ICAM-I and VCAM-I parallels the development of clinical disease onset, but persists on elevated levels also in the phase of clinical remission. However, the composition of infiltrating T cells found in the developing versus resolving lesion phase changed over time, containing increased numbers of regulatory T cells (FoxP3) only in the phase of clinical remission. In order to test the relevance of the expression of cell adhesion molecules, animals were treated with purified antibodies to ICAM-I and VCAM-I either in the phase of active disease or in early remission. Treatment with a blocking ICAM-I antibody in the phase of disease progression led to a milder disease course. However, administration during early clinical remission aggravates clinical symptoms. Treatment with anti-VCAM-I at different timepoints had no significant effect on the disease course. In summary, our results indicate that adhesion molecules are not only important for capture and migration of pro-inflammatory T cells into the central nervous system, but also permit access of anti-inflammatory cells, such as regulatory T cells. Therefore it is likely to assume that intervention at the blood brain barrier is time dependent and could result in different therapeutic outcomes depending on the phase of CNS lesion development

Jet energy measurement with the ATLAS detector in proton-proton collisions at root s=7 TeV

The jet energy scale and its systematic uncertainty are determined for jets measured with the ATLAS detector at the LHC in proton-proton collision data at a centre-of-mass energy of √s = 7TeV corresponding to an integrated luminosity of 38 pb-1. Jets are reconstructed with the anti-kt algorithm with distance parameters R=0. 4 or R=0. 6. Jet energy and angle corrections are determined from Monte Carlo simulations to calibrate jets with transverse momenta pT≥20 GeV and pseudorapidities {pipe}η{pipe}<4. 5. The jet energy systematic uncertainty is estimated using the single isolated hadron response measured in situ and in test-beams, exploiting the transverse momentum balance between central and forward jets in events with dijet topologies and studying systematic variations in Monte Carlo simulations. The jet energy uncertainty is less than 2. 5 % in the central calorimeter region ({pipe}η{pipe}<0. 8) for jets with 60≤pT<800 GeV, and is maximally 14 % for pT<30 GeV in the most forward region 3. 2≤{pipe}η{pipe}<4. 5. The jet energy is validated for jet transverse momenta up to 1 TeV to the level of a few percent using several in situ techniques by comparing a well-known reference such as the recoiling photon pT, the sum of the transverse momenta of tracks associated to the jet, or a system of low-pT jets recoiling against a high-pT jet. More sophisticated jet calibration schemes are presented based on calorimeter cell energy density weighting or hadronic properties of jets, aiming for an improved jet energy resolution and a reduced flavour dependence of the jet response. The systematic uncertainty of the jet energy determined from a combination of in situ techniques is consistent with the one derived from single hadron response measurements over a wide kinematic range. The nominal corrections and uncertainties are derived for isolated jets in an inclusive sample of high-pT jets. Special cases such as event topologies with close-by jets, or selections of samples with an enhanced content of jets originating from light quarks, heavy quarks or gluons are also discussed and the corresponding uncertainties are determined. © 2013 CERN for the benefit of the ATLAS collaboration

Observation of associated near-side and away-side long-range correlations in √sNN=5.02 TeV proton-lead collisions with the ATLAS detector

Two-particle correlations in relative azimuthal angle (Δϕ) and pseudorapidity (Δη) are measured in √sNN=5.02  TeV p+Pb collisions using the ATLAS detector at the LHC. The measurements are performed using approximately 1  μb-1 of data as a function of transverse momentum (pT) and the transverse energy (ΣETPb) summed over 3.1<η<4.9 in the direction of the Pb beam. The correlation function, constructed from charged particles, exhibits a long-range (2<|Δη|<5) “near-side” (Δϕ∼0) correlation that grows rapidly with increasing ΣETPb. A long-range “away-side” (Δϕ∼π) correlation, obtained by subtracting the expected contributions from recoiling dijets and other sources estimated using events with small ΣETPb, is found to match the near-side correlation in magnitude, shape (in Δη and Δϕ) and ΣETPb dependence. The resultant Δϕ correlation is approximately symmetric about π/2, and is consistent with a dominant cos⁡2Δϕ modulation for all ΣETPb ranges and particle pT