Ciprofibrate quantification in human plasma by high-performance liquid chromatography coupled with electrospray tandem mass spectrometry for pharmacokinetic studies

A rapid, sensitive and specific method for quantifying ciprofibrate in human plasma using bezafibrate as the internal standard (IS) is described. The sample was acidified prior extraction with formic acid (88%). The analyte and the IS were extracted from plasma by liquid-liquid extraction using an organic solvent (diethyl ether/dichloromethane 70/30 (v/v)). The extracts were analyzed by high performance liquid chromatography coupled with electrospray tandem mass spectrometry (HPLC-MS/MS). Chromatography was performed using Genesis C18 4 mu m analytical column (4.6 x 150 mm i.d.) and a mobile phase consisting of acetonitrile/water (70/30, v/v) and 1 mM acetic acid. The method had a chromatographic run time of 3.4 min and a linear calibration curve over the range 0.1-60 mu g/mL (r > 0.99). The limit of quantification was 0.1 mu g/mL. The intra- and interday accuracy and precision values of the assay were less than 13.5%. The stability tests indicated no significant degradation. The recovery of ciprofibrate was 81.2%, 73.3% and 76.2% for the 0.3, 5.0 and 48.0 ng/mL standard concentrations, respectively. For ciprofibrate, the optimized parameters of the declustering potential, collision energy and collision exit potential were -51 V, -16 eV and -5 V, respectively. The method was also validated without the use of the internal standard. This HPLC-MS/MS procedure was used to assess the bioequivalence of two ciprofibrate 100 mg tablet formulations in healthy volunteers of both sexes. The following pharmacokinetic parameters were obtained from the ciprofibrate plasma concentration vs. time curves: AUC(last), AUC(0-168 h), C(max) and T(max). The geometric mean with corresponding 90% confidence interval (CI) for test/reference percent ratios were 93.80% (90% CI = 88.16-99.79%) for C(max), 98.31% (90% CI = 94.91-101.83%) for AUC(last) and 97.67% (90% CI = 94.45-101.01%) for AUC(0-168 h). Since the 90% Cl for AUC(last), AUC(0-168 h) and C(max) ratios were within the 80-125% interval proposed by the US FDA, it was concluded that ciprofibrate (Lipless (R) 100 mg tablet) formulation manufactured by Biolab Sanus Farmaceutica Ltda. is bioequivalent to the Oroxadin (R) (100 mg tablet) formulation for both the rate and the extent of absorption. (C) 2011 Published by Elsevier B.V.

Disentangling static and dynamic effects of low breakup threshold in fusion reactions

A new technique to analyze fusion data is developed. From experimental cross sections and results of coupled-channel calculations a dimensionless function is constructed. In collisions of strongly bound nuclei this quantity is very close to a universal function of a variable related to the collision energy, whereas for weakly bound projectiles the effects of breakup coupling are measured by the deviations with respect to this universal function. This technique is applied to collisions of stable and unstable weakly bound isotopes.

CMS physics technical design report, volume II: Physics performance

CMS is a general purpose experiment, designed to study the physics of pp collisions at 14 TeV at the Large Hadron Collider ( LHC). It currently involves more than 2000 physicists from more than 150 institutes and 37 countries. The LHC will provide extraordinary opportunities for particle physics based on its unprecedented collision energy and luminosity when it begins operation in 2007. The principal aim of this report is to present the strategy of CMS to explore the rich physics programme offered by the LHC. This volume demonstrates the physics capability of the CMS experiment. The prime goals of CMS are to explore physics at the TeV scale and to study the mechanism of electroweak symmetry breaking - through the discovery of the Higgs particle or otherwise. To carry out this task, CMS must be prepared to search for new particles, such as the Higgs boson or supersymmetric partners of the Standard Model particles, from the start- up of the LHC since new physics at the TeV scale may manifest itself with modest data samples of the order of a few fb(-1) or less. The analysis tools that have been developed are applied to study in great detail and with all the methodology of performing an analysis on CMS data specific benchmark processes upon which to gauge the performance of CMS. These processes cover several Higgs boson decay channels, the production and decay of new particles such as Z' and supersymmetric particles, B-s production and processes in heavy ion collisions. The simulation of these benchmark processes includes subtle effects such as possible detector miscalibration and misalignment. Besides these benchmark processes, the physics reach of CMS is studied for a large number of signatures arising in the Standard Model and also in theories beyond the Standard Model for integrated luminosities ranging from 1 fb(-1) to 30 fb(-1). The Standard Model processes include QCD, B-physics, diffraction, detailed studies of the top quark properties, and electroweak physics topics such as the W and Z(0) boson properties. The production and decay of the Higgs particle is studied for many observable decays, and the precision with which the Higgs boson properties can be derived is determined. About ten different supersymmetry benchmark points are analysed using full simulation. The CMS discovery reach is evaluated in the SUSY parameter space covering a large variety of decay signatures. Furthermore, the discovery reach for a plethora of alternative models for new physics is explored, notably extra dimensions, new vector boson high mass states, little Higgs models, technicolour and others. Methods to discriminate between models have been investigated. This report is organized as follows. Chapter 1, the Introduction, describes the context of this document. Chapters 2-6 describe examples of full analyses, with photons, electrons, muons, jets, missing E-T, B-mesons and tau's, and for quarkonia in heavy ion collisions. Chapters 7-15 describe the physics reach for Standard Model processes, Higgs discovery and searches for new physics beyond the Standard Model.

Jet momentum dependence of jet quenching in PbPb collisions at root s(NN)=2.76 TeV

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

A search for excited leptons in pp collisions at root s=7 TeV

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Dependence on pseudorapidity and on centrality of charged hadron production in PbPb collisions at root s(NN)=2.76 TeV

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Disappearance of squeezed back-to-back correlations: a new signal of hadron freeze-out from a supercooled quark gluon plasma

We briefly discuss four different possible types of transitions from quark to hadronic matter and their characteristic signatures in terms of correlations. We also highlight the effects arising from mass modification of hadrons in hot and dense hadronic matter, as well as their quantum statistical consequences: the appearance of squeezed quantum states and the associated experimental signatures, i.e., the back-to-back correlations of particle-antiparticle pairs. We briefly review the theoretical results of these squeezed quanta, generated by in-medium modified masses, starting from the first indication of the existence of surprising particle-antiparticle correlations, and ending by considering the effects of chiral dynamics on these correlation patterns. Nevertheless, a prerequisite for such a signature is the experimental verification of its observability. Therefore, the experimental observation of back-to-back correlations in high energy heavy ion reactions would be a unique signature, proving the existence of in-medium mass modification of hadronic states. on the other hand, their disappearance at some threshold centrality or collision energy would indicate that the hadron formation mechanism would have qualitatively changed: asymptotic hadrons above such a threshold are not formed from medium modified hadrons anymore, but rather by new degrees of freedom characterizing the medium. Furthermore, the disappearance of the squeezed BBC could also serve as a signature of a sudden, non-equilibrium hadronization scenario from a supercooled quark-gluon plasma phase.

Studies of jet quenching using isolated-photon+jet correlations in PbPb and pp collisions at sNN=2.76TeV

Results from the first study of isolated-photon+jet correlations in relativistic heavy ion collisions are reported. The analysis uses data from PbPb collisions at a centre-of-mass energy of 2.76TeV per nucleon pair corresponding to an integrated luminosity of 150μb-1 recorded by the CMS experiment at the LHC. For events containing an isolated photon with transverse momentum pTγ>60GeV/c and an associated jet with pTJet>30GeV/c, the photon+jet pT imbalance is studied as a function of collision centrality and compared to pp data and pythia calculations at the same collision energy. Using the pTγ of the isolated photon as an estimate of the momentum of the associated parton at production, this measurement allows an unbiased characterisation of the in-medium parton energy loss. For more central PbPb collisions, a significant decrease in the ratio pTJet/pTγ relative to that in the pythia reference is observed. Furthermore, significantly more pTγ>60GeV/c photons in PbPb are observed not to have an associated pTJet>30GeV/c jet, compared to the reference. However, no significant broadening of the photon+jet azimuthal correlation is observed. © 2012 CERN.

Evolution of pi(0) Suppression in Au plus Au Collisions from root s(NN)=39 to 200 GeV

Neutral-pion pi(0) spectra were measured at midrapidity (vertical bar y vertical bar < 0.35) in Au + Au collisions at root s(NN) = 39 and 62.4 GeV and compared with earlier measurements at 200 GeV in a transverse-momentum range of 1 < p(T) < 10 GeV/c. The high-p(T) tail is well described by a power law in all cases, and the powers decrease significantly with decreasing center-of-mass energy. The change of powers is very similar to that observed in the corresponding spectra for p + p collisions. The nuclear modification factors (RAA) show significant suppression, with a distinct energy, centrality, and p(T) dependence. Above p(T) = 7 GeV/c, R-AA is similar for root sNN = 62.4 and 200 GeV at all centralities. Perturbative-quantum-chromodynamics calculations that describe R-AA well at 200 GeV fail to describe the 39 GeV data, raising the possibility that, for the same p(T) region, the relative importance of initial-state effects and soft processes increases at lower energies. The p(T) range where pi(0) spectra in central Au + Au collisions have the same power as in p + p collisions is approximate to 5 and 7 GeV/c for root sNN = 200 and 62.4 GeV, respectively. For the root sNN = 39 GeV data, it is not clear whether such a region is reached, and the x(T) dependence of the x(T)-scaling power-law exponent is very different from that observed in the root sNN = 62 and 200 GeV data, providing further evidence that initial-state effects and soft processes mask the in-medium suppression of hardscattered partons to higher p(T) as the collision energy decreases.

Inclusive charged hadron elliptic flow in Au+Au collisions at root s(NN)=7.7-39 GeV

A systematic study is presented for centrality, transverse momentum (p(T)), and pseudorapidity (eta) dependence of the inclusive charged hadron elliptic flow (v(2)) at midrapidity (vertical bar eta vertical bar < 1.0) in Au + Au collisions at root s(NN) = 7.7, 11.5, 19.6, 27, and 39 GeV. The results obtained with different methods, including correlations with the event plane reconstructed in a region separated by a large pseudorapidity gap and four-particle cumulants (v(2){4}), are presented to investigate nonflow correlations and v(2) fluctuations. We observe that the difference between v(2){2} and v(2){4} is smaller at the lower collision energies. Values of v(2), scaled by the initial coordinate space eccentricity, v(2)/epsilon, as a function of p(T) are larger in more central collisions, suggesting stronger collective flow develops in more central collisions, similar to the results at higher collision energies. These results are compared to measurements at higher energies at the Relativistic Heavy Ion Collider (root s(NN) = 62.4 and 200 GeV) and at the Large Hadron Collider (Pb + Pb collisions at root s(NN) = 2.76 TeV). The v(2)(pT) values for fixed pT rise with increasing collision energy within the pT range studied (<2 GeV/c). A comparison to viscous hydrodynamic simulations is made to potentially help understand the energy dependence of v(2)(pT). We also compare the v(2) results to UrQMD and AMPT transport model calculations, and physics implications on the dominance of partonic versus hadronic phases in the system created at beam energy scan energies are discussed.

Quality evaluation of tandem mass spectral libraries

Tandem mass spectral libraries are gaining more and more importance for the identification of unknowns in different fields of research, including metabolomics, forensics, toxicology, and environmental analysis. Particularly, the recent invention of reliable, robust, and transferable libraries has increased the general acceptance of these tools. Herein, we report on results obtained from thorough evaluation of the match reliabilities of two tandem mass spectral libraries: the MSforID library established by the Oberacher group in Innsbruck and the Weinmann library established by the Weinmann group in Freiburg. Three different experiments were performed: (1) Spectra of the libraries were searched against their corresponding library after excluding either this single compound-specific spectrum or all compound-specific spectra prior to searching; (2) the libraries were searched against each other using either library as reference set or sample set; (3) spectra acquired on different mass spectrometric instruments were matched to both libraries. Almost 13,000 tandem mass spectra were included in this study. The MSforID search algorithm was used for spectral matching. Statistical evaluation of the library search results revealed that principally both libraries enable the sensitive and specific identification of compounds. Due to higher mass accuracy of the QqTOF compared with the QTrap instrument, matches to the MSforID library were more reliable when comparing spectra with both libraries. Furthermore, only the MSforID library was shown to be efficiently transferable to different kinds of tandem mass spectrometers, including "tandem-in-time" instruments; this is due to the coverage of a large range of different collision energy settings-including the very low range-which is an outstanding characteristics of the MSforID library.

Measurement of negatively charged pion spectra in inelastic p+p interactions at plab = 20, 31, 40, 80 and 158 GeV/c

We present experimental results on inclusive spectra and mean multiplicities of negatively charged pions produced in inelastic p+p interactions at incident projectile momenta of 20, 31, 40, 80 and 158GeV/c (√s = 6.3, 7.7,8.8, 12.3 and 17.3GeV, respectively). The measurements were performed using the large acceptance NA61/SHINE hadron spectrometer at the CERN super proton synchrotron. Two-dimensional spectra are determined in terms of rapidity and transverse momentum. Their properties such as the width of rapidity distributions and the inverse slope parameter of transverse mass spectra are extracted and their collision energy dependences are presented. The results on inelastic p+p interactions are compared with the corresponding data on central Pb+Pb collisions measured by the NA49 experiment at the CERNSPS. The results presented in this paper are part of the NA61/SHINE ion program devoted to the study of the properties of the onset of deconfinement and search for the critical point of strongly interacting matter. They are required for interpretation of results on nucleus–nucleus and proton–nucleus collisions.

Enhancement of hydrogen physisorption on single-walled carbon nanotubes resulting from defects created by carbon bombardment

The defect effect on hydrogen adsorption on single-walled carbon nanotubes (SWNTs) has been studied by using extensive molecular dynamics simulations and density functional theory (DFT) calculations. It indicates that the defects created on the exterior wall of the SWNTs by bombarding the tube wall with carbon atoms and C-2 dimers at a collision energy of 20 eV can enhance the hydrogen adsorption potential of the SWNTs substantially. The average adsorption energy for a H-2 molecule adsorbed on the exterior wall of a defected (10,10) SWNT is similar to 150 meV, while that for a H-2 molecule adsorbed on the exterior wall of a perfect (10,10) SWNT is similar to 104 meV. The H-2 sticking coefficient is very sensitive to temperature, and has a maximum value around 70 to 90 K. The electron density contours, the local density of states, and the electron transfers obtained from the DFT calculations clearly indicate that the H-2 molecules are all physisorbed on the SWNTs. At temperatures above 200 K, most of the H-2 molecules adsorbed on the perfect SWNT are soon desorbed, but the H-2 molecules can still remain on the defected SWNTs at 300 K. The detailed processes of H-2 molecules adsorbing on and desorbing from the (10,10) SWNTs are demonstrated.

Formation of Polycyclic Aromatic Hydrocarbons and Nitrogen Containing Polycyclic Aromatic Compounds in Titan's Atmosphere, the Interstellar Medium and Combustion

Several different mechanisms leading to the formation of (substituted) naphthalene and azanaphthalenes were examined using theoretical quantum chemical calculations. As a result, a series of novel synthetic routes to Polycyclic Aromatic Hydrocarbons (PAHs) and Nitrogen Containing Polycyclic Aromatic Compounds (N-PACs) have been proposed. On Earth, these aromatic compounds originate from incomplete combustion and are released into our environment, where they are known to be major pollutants, often with carcinogenic properties. In the atmosphere of a Saturn's moon Titan, these PAH and N-PACs are believed to play a critical role in organic haze formation, as well as acting as chemical precursors to biologically relevant molecules. The theoretical calculations were performed by employing the ab initio G3(MP2,CC)/B3LYP/6-311G** method to effectively probe the Potential Energy Surfaces (PES) relevant to the PAH and N-PAC formation. Following the construction of the PES, Rice-Ramsperger-Kassel-Markus (RRKM) theory was used to evaluate all unimolecular rate constants as a function of collision energy under single-collision conditions. Branching ratios were then evaluated by solving phenomenological rate expressions for the various product concentrations. The most viable pathways to PAH and N-PAC formation were found to be those where the initial attack by the ethynyl (C2H) or cyano (CN) radical toward a unsaturated hydrocarbon molecule led to the formation of an intermediate which could not effectively lose a hydrogen atom. It is not until ring cyclization has occurred, that hydrogen elimination leads to a closed shell product. By quenching the possibility of the initial hydrogen atom elimination, one of the most competitive processes preventing the PAH or N-PAC formation was avoided, and the PAH or N-PAC formation was allowed to proceed. It is concluded that these considerations should be taken into account when attempting to explore any other potential routes towards aromatic compounds in cold environments, such as on Titan or in the interstellar medium.

Excitation of Phonons in Solids and Nanostructures by Intense Laser and XUV Pulses and by Low Energy Atomic Collision

Intensive, ultrakurze Laserpulse regen Festkörper in einen Zustand an, in dem die Elektronen hohe Temperaturen erlangen, während das Gitter kalt bleibt. Die heißen Elektronen beeinflussen das sog. Laser-angeregte interatomare Potential bzw. die Potentialenergiefläche, auf der die Ionen sich bewegen. Dieses kann neben anderen ultrakurzen Prozessen zu Änderungen der Phononfrequenzen (phonon softening oder phonon hardening) führen. Viele ultrakurze strukturelle Phänomene in Festkörpern hängen bei hohen Laseranregungen von Änderungen der Phononfrequenzen bei niedrigeren Anregungen ab. Um die Laser-bedingten Änderungen des Phononenspektrums von Festkörpern beschreiben zu können, haben wir ein auf Temperatur-abhängiger Dichtefunktionaltheorie basierendes Verfahren entwickelt. Die dramatischen Änderungen nach einer Laseranregung in der Potentialenergiefläche werden durch die starke Veränderung der Zustandsdichte und der Besetzungen der Elektronen hervorgerufen. Diese Änderungen in der Zustandsdichte und den Besetzungszahlen können wir mit unserer Methode berechnen, um dann damit das Verhalten der Phononen nach einer Laseranregung zu analysieren. Auf diese Art und Weise studierten wir den Einfluss einer Anregung mit einem intensiven, ultrakurzen Laserpuls auf repräsentative Phonon Eigenmoden in Magnesium, Kupfer und Aluminium. Wir stellten dabei in manchen Gitterschwingungen entweder eine Abnahme (softening) und in anderen eine Zunahme (hardening) der Eigenfrequenz fest. Manche Moden zeigten bei Variation der Laseranregungsstärke sogar beide Verhaltensweisen. Das eine Phonon-Eigenmode ein hardening und softening zeigen kann, wird durch das Vorhandensein von van Hove Singularitäten in der elektronischen Zustandsdichte des betrachteten Materials erklärt. Für diesen Fall stellt unser Verfahren zusammen mit der Sommerfeld-Entwicklung die Eigenschaften der Festkörper Vibrationen in Verbindung mit den Laser induzierten Veränderungen in den elektronischen Besetzungen für verschiedene Phonon-eingefrorene Atomkonfigurationen. Auch die absolute Größe des softening und hardening wurde berechnet. Wir nehmen an, dass unsere Theorie Licht in die Effekte der Laseranregung von verschiedenen Materialien bringt. Außerdem studierten wir mit Hilfe von Dichtefunktionaltheorie die strukturellen Material-Eigenschaften, die durch kurze XUV Pulse induziert werden. Warme dichte Materie in Ultrakurzpuls angeregten Magnesium wurde analysiert und verglichen mit den Ergebnissen bei durch Laser Anregung bedingten Änderungen. Unter Verwendung von elektronischer-Temperatur-abhängiger Dichtefunktionaltheorie wurden die Änderungen in den Bindungseigenschaften von warmen dichten Magnesium studiert. Wir stellten dabei beide Effekte, Verstärkung und Abschwächung von Bindungen, bei jeweils verschiedenen Phonon Eigenmoden von Magnesium auf Grund von der Erzeugung von Rumpflöchern und dem Vorhandensein von heißen Elektronen fest. Die zusätzliche Erzeugung von heißen Elektronen führt zu einer Änderung der Bindungscharakteristik, die der Änderung, die durch die bereits vorhandenen Rumpflöcher hervorgerufen wurde, entgegen wirkt. Die thermischen Eigenschaften von Nanostrukturen sind teilweise sehr wichtig für elektronische Bauteile. Wir studierten hier ebenfalls den Effekt einer einzelnen Graphen Lage auf Kupfer. Dazu untersuchten wir mit Dichtefunktionaltheorie die strukturellen- und Schwingungseigenschaften von Graphen auf einem Kupfer Substrat. Wir zeigen, dass die schwache Wechselwirkung zwischen Graphen und Kupfer die Frequenz der aus der Ebene gerichteten akustischen Phonon Eigenmode anhebt und die Entartung zwischen den aus der Ebene gerichteten akustischen und optischen Phononen im K-Punkt des Graphen Spektrums aufhebt. Zusätzlich führten wir ab initio Berechnungen zur inelastischen Streuung eines Helium Atoms mit Graphen auf einem Kuper(111) Substrat durch. Wir berechneten dazu das Leistungsspektrum, das uns eine Idee über die verschiedenen Gitterschwingungen des Graphene-Kuper(111) Systems gibt, die durch die Kollision des Helium Atom angeregt werden. Wir brachten die Positionen der Peaks im Leistungsspektrum mit den Phonon Eigenfrequenzen, die wir aus den statischen Rechnungen erhalten haben, in Beziehung. Unsere Ergebnisse werden auch verglichen mit den Ergebnissen experimenteller Daten zur Helium Streuung an Graphen-Kupfer(111) Oberflächen.