Protective Mechanisms of the Mitochondrial-Derived Peptide Humanin in Oxidative and Endoplasmic Reticulum Stress in RPE Cells

Age-related macular degeneration (AMD) is the leading cause of severe and irreversible vision loss and is characterized by progressive degeneration of the retina resulting in loss of central vision. The retinal pigment epithelium (RPE) is a critical site of pathology of AMD. Mitochondria and the endoplasmic reticulum which lie in close anatomic proximity to each other are targets of oxidative stress and endoplasmic reticulum (ER) stress, respectively, and contribute to the progression of AMD. The two organelles exhibit close interactive function via various signaling mechanisms. Evidence for ER-mitochondrial crosstalk in RPE under ER stress and signaling pathways of apoptotic cell death is presented. The role of humanin (HN), a prominent member of a newly discovered family of mitochondrial-derived peptides (MDPs) expressed from an open reading frame of mitochondrial 16S rRNA, in modulation of ER and oxidative stress in RPE is discussed. HN protected RPE cells from oxidative and ER stress-induced cell death by upregulation of mitochondrial GSH, inhibition of ROS generation, and caspase 3 and 4 activation. The underlying mechanisms of ER-mitochondrial crosstalk and modulation by exogenous HN are discussed. The therapeutic use of HN and related MDPs could potentially prove to be a valuable approach for treatment of AMD

Performance of the ALICE Experiment at the CERN LHC

ALICE is the heavy-ion experiment at the CERN Large Hadron Collider. The experiment continuously took data during the first physics campaign of the machine from fall 2009 until early 2013, using proton and lead-ion beams. In this paper we describe the running environment and the data handling procedures, and discuss the performance of the ALICE detectors and analysis methods for various physics observables.ALICE is the heavy-ion experiment at the CERN Large Hadron Collider. The experiment continuously took data during the first physics campaign of the machine from fall 2009 until early 2013, using proton and lead-ion beams. In this paper we describe the running environment and the data handling procedures, and discuss the performance of the ALICE detectors and analysis methods for various physics observables.ALICE is the heavy-ion experiment at the CERN Large Hadron Collider. The experiment continuously took data during the first physics campaign of the machine from fall 2009 until early 2013, using proton and lead-ion beams. In this paper we describe the running environment and the data handling procedures, and discuss the performance of the ALICE detectors and analysis methods for various physics observables

Charge correlations using the balance function in Pb?Pb collisions at ?sNN = 2.76 TeV

In high-energy heavy-ion collisions, the correlations between the emitted particles can be used as a probe to gain insight into the charge creation mechanisms. In this article, we report the first results of such studies using the electric charge balance function in the relative pseudorapidity \Delta\eta and azimuthal angle \Delta\phi in Pb-Pb collisions at sqrt{s_{NN}} = 2.76 TeV with the ALICE detector at the Large Hadron Collider. The width of the balance function decreases with growing centrality (i.e. for more central collisions) in both projections. This centrality dependence is not reproduced by HIJING, while AMPT, a model which incorporates strings and parton rescattering, exhibits qualitative agreement with the measured correlations in \Delta\phi but fails to describe the correlations in \Delta\eta. A thermal blast wave model incorporating local charge conservation and tuned to describe the p_T spectra and v_2 measurements reported by ALICE, is used to fit the centrality dependence of the width of the balance function and to extract the average separation of balancing charges at freeze-out. The comparison of our results with measurements at lower energies reveals an ordering with sqrt{s_{NN}}: the balance functions become narrower with increasing energy for all centralities. This is consistent with the effect of larger radial flow at the LHC energies but also with the late stage creation scenario of balancing charges. However, the relative decrease of the balance function widths in \Delta\eta and \Delta\phi with centrality from the highest SPS to the LHC energy exhibits only small differences. This observation cannot be interpreted solely within the framework where the majority of the charge is produced at a later stage in the evolution of the heavy-ion collision

Long-range angular correlations of π, K and p in p–Pb collisions at sNN\sqrt{s_{NN}} = 5.02 TeV

Angular correlations between unidentified charged trigger particles and various species of charged associated particles (unidentified particles, pions, kaons, protons and antiprotons) are measured by the ALICE detector in p-Pb collisions at a nucleon--nucleon centre-of-mass energy of 5.02 TeV in the transverse-momentum range 0.3 < $p_T$ < 4 GeV/c. The correlations expressed as associated yield per trigger particle are obtained in the pseudorapidity range |$\eta_{lab}$| < 0.8. Fourier coefficients are extracted from the long-range correlations projected onto the azimuthal angle difference and studied as a function of $p_T$ and in intervals of event multiplicity. In high-multiplicity events, the second-order coefficient for protons, $v_2^p$, is observed to be smaller than that for pions, $v_2^\pi$, up to about $p_T$ = 2 GeV/c. To reduce correlations due to jets, the per-trigger yield measured in low-multiplicity events is subtracted from that in high-multiplicity events. A two-ridge structure is obtained for all particle species. The Fourier decomposition of this structure shows that the second-order coefficients for pions and kaons are similar. The $v_2^p$ is found to be smaller at low $p_T$ and larger at higher $p_T$ than $v_2^\pi$, with a crossing occurring at about 2 GeV. This is qualitatively similar to the elliptic-flow pattern observed in heavy-ion collisions. A mass ordering effect at low transverse momenta is consistent with expectations from hydrodynamic model calculations assuming a collectively expanding system.Angular correlations between unidentified charged trigger particles and various species of charged associated particles (unidentified particles, pions, kaons, protons and antiprotons) are measured by the ALICE detector in p-Pb collisions at a nucleon-nucleon centre-of-mass energy of 5.02 TeV in the transverse-momentum range $0.3 < p_{\rm T} < 4$ GeV/$c$. The correlations expressed as associated yield per trigger particle are obtained in the pseudorapidity range $|\eta_{\rm lab}|<0.8$. Fourier coefficients are extracted from the long-range correlations projected onto the azimuthal angle difference and studied as a function of $p_{\rm T}$ and in intervals of event multiplicity. In high-multiplicity events, the second-order coefficient for protons, $v_2^p$, is observed to be smaller than that for pions, $v_2^\pi$, up to about $p_{\rm T} = 2$ GeV/$c$. To reduce correlations due to jets, the per-trigger yield measured in low-multiplicity events is subtracted from that in high-multiplicity events. A two-ridge structure is obtained for all particle species. The Fourier decomposition of this structure shows that the second-order coefficients for pions and kaons are similar. The $v_2^p$ is found to be smaller at low $p_{\rm T}$ and larger at higher $p_{\rm T}$ than $v_2^pi$, with a crossing occurring at about 2 GeV. This is qualitatively similar to the elliptic-flow pattern observed in heavy-ion collisions. A mass ordering effect at low transverse momenta is consistent with expectations from hydrodynamic model calculations assuming a collectively expanding system.Angular correlations between unidentified charged trigger particles and various species of charged associated particles (unidentified particles, pions, kaons, protons and antiprotons) are measured by the ALICE detector in p–Pb collisions at a nucleon–nucleon centre-of-mass energy of 5.02 TeV in the transverse-momentum range 0.3<pT<4 GeV/c . The correlations expressed as associated yield per trigger particle are obtained in the pseudorapidity range |ηlab|<0.8 . Fourier coefficients are extracted from the long-range correlations projected onto the azimuthal angle difference and studied as a function of pT and in intervals of event multiplicity. In high-multiplicity events, the second-order coefficient for protons, v2p , is observed to be smaller than that for pions, v2π , up to about pT=2 GeV/c . To reduce correlations due to jets, the per-trigger yield measured in low-multiplicity events is subtracted from that in high-multiplicity events. A two-ridge structure is obtained for all particle species. The Fourier decomposition of this structure shows that the second-order coefficients for pions and kaons are similar. The v2p is found to be smaller at low pT and larger at higher pT than v2π , with a crossing occurring at about 2 GeV/c . This is qualitatively similar to the elliptic-flow pattern observed in heavy-ion collisions. A mass ordering effect at low transverse momenta is consistent with expectations from hydrodynamic model calculations assuming a collectively expanding system

Measurement of charged jet suppression in Pb-Pb collisions at √sNN = 2.76 TeV

A measurement of the transverse momentum spectra of jets in Pb-Pb collisions at sNN−−−√=2.76 TeV is reported. Jets are reconstructed from charged particles using the anti-kT jet algorithm with jet resolution parameters R of 0.2 and 0.3 in pseudo-rapidity |η|<0.5. The transverse momentum pT of charged particles is measured down to 0.15 GeV/c which gives access to the low pT fragments of the jet. Jets found in heavy-ion collisions are corrected event-by-event for average background density and on an inclusive basis (via unfolding) for residual background fluctuations and detector effects. A strong suppression of jet production in central events with respect to peripheral events is observed. The suppression is found to be similar to the suppression of charged hadrons, which suggests that substantial energy is radiated at angles larger than the jet resolution parameter R=0.3 considered in the analysis. The fragmentation bias introduced by selecting jets with a high pT leading particle, which rejects jets with a soft fragmentation pattern, has a similar effect on the jet yield for central and peripheral events. The ratio of jet spectra with R=0.2 and R=0.3 is found to be similar in Pb-Pb and simulated PYTHIA pp events, indicating no strong broadening of the radial jet structure in the reconstructed jets with R<0.3.

Multiplicity dependence of the average transverse momentum in pp, p-Pb, and Pb-Pb collisions at the LHC

The average transverse momentum versus the charged-particle multiplicity $N_{ch}$ was measured in p-Pb collisions at a collision energy per nucleon-nucleon pair $\sqrt{s_{NN}}$ = 5.02 TeV and in pp collisions at collision energies of $\sqrt{s}$ = 0.9, 2.76, and 7 Tev in the kinematic range 0.15 with $N_{ch}$ is observed, which is much stronger than that measured in Pb-Pb collisions. For pp collisions, this could be attributed, within a model of hadronizing strings, to multiple-parton interactions and to a final-state color reconnection mechanism. The data in p-Pb and Pb-Pb collisions cannot be described by an incoherent superposition of nucleon-nucleon collisions and pose a challenge to most of the event generators