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This corrects the article DOI: 10.1103/PhysRevLett.89.132301.
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This corrects the article DOI: 10.1103/PhysRevLett.92.062301.
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The anticancer agent docetaxel shows significant inter-individual variation in its pharmacokinetic and toxicity profile. Thalidomide is an active anticancer agent and also shows wide pharmacological variation. Past pharmacogenetic research has not explained this variation. Patients with prostate cancer enrolled in a randomized phase II trial using docetaxel and thalidomide versus docetaxel alone were genotyped using the Affymetrix DMET 1.0 platform, which tests for 1256 genetic variations in 170 drug disposition genes. Genetic polymorphisms were analyzed for associations with clinical response and toxicity. In all, 10 single-nucleotide polymorphisms (SNPs) in three genes were potentially associated with response to therapy: peroxisome proliferator-activated receptor-delta (PPAR-delta), sulfotransferase family, cytosolic, 1C, member 2 (SULT1C2) and carbohydrate (chondroitin 6) sulfotransferase 3 (CHST3). In addition, 11 SNPs in eight genes were associated with toxicities to treatment: spastic paraplegia 7 (pure and complicated autosomal recessive) (SPG7), CHST3, cytochrome P450, family 2, subfamily D, polypeptide 6 (CYP2D6), N-acetyltransferase 2 (arylamine N-acetyltransferase) (NAT2), ATP-binding cassette, sub-family C (CFTR/MRP), member 6 (ABCC6), ATPase, Cu++ transporting, alpha polypeptide (ATP7A), cytochrome P450, family 4, subfamily B, polypeptide 1 (CYP4B1) and solute carrier family 10 (sodium/bile acid cotransporter family), member 2 (SLC10A2). Genotyping results between drug metabolizing enzymes and transporters (DMET) and direct sequencing showed >96% of concordance. These findings highlight the role that non-CYP450 metabolizing enzymes and transporters may have in the pharmacology of docetaxel and thalidomide.
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PPAR delta/genética , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/genética , Sulfotransferases/genética , Taxoides/uso terapêutico , Talidomida/uso terapêutico , Adulto , Idoso , Docetaxel , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Sequência com Séries de Oligonucleotídeos/métodos , Orquiectomia , Farmacogenética , Polimorfismo de Nucleotídeo Único , Taxoides/efeitos adversos , Taxoides/farmacocinética , Talidomida/efeitos adversos , Talidomida/farmacocinética , Carboidrato SulfotransferasesRESUMO
Transverse momentum spectra of pi+/-, p, and p up to 12 GeV/c at midrapidity in centrality selected Au + Au collisions at square root sNN=200 GeV are presented. In central Au + Au collisions, both pi +/- and p(p) show significant suppression with respect to binary scaling at pT approximately >4 GeV/c. Protons and antiprotons are less suppressed than pi+/-, in the range 1.5 approximately < pT approximately < 6 GeV/c. The pi-/pi+ and p/p ratios show at most a weak pT dependence and no significant centrality dependence. The p/pi ratios in central Au + Au collisions approach the values in p + p and d + Au collisions at pT approximately >5 GeV/c. The results at high pT indicate that the partonic sources of pi+/-, p, and p have similar energy loss when traversing the nuclear medium.
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Charged hadrons in [EQUATION: SEE TEXT] associated with particles of [EQUATION: SEE TEXT] are reconstructed in pp and Au+Au collisions at sqrt[sNN]=200 GeV. The associated multiplicity and p magnitude sum are found to increase from pp to central Au+Au collisions. The associated p distributions, while similar in shape on the nearside, are significantly softened on the awayside in central Au+Au relative to pp and not much harder than that of inclusive hadrons. The results, consistent with jet quenching, suggest that the awayside fragments approach equilibration with the medium traversed.
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The amelogenin proteins regulate enamel mineral formation in the developing tooth. The human AMELX gene, which encodes the amelogenin proteins, is located within an intron of the Arhgap 6 gene. ARHGAP 6 encodes a Rho GAP, which regulates activity of Rho A, a small G protein involved in intracellular signal transduction. Mice were generated in which the entire ARHGAP 6 gene was deleted by Cre-mediated recombination, which also removed the nested Amel X gene. Enamel from these mice appeared chalky white, and the molars showed excessive wear. The enamel layer was hypoplastic and non-prismatic, whereas other dental tissues had normal morphology. This phenotype is similar to that reported for Amel X null mice, which have a short deletion that removed the region surrounding the translation initiation site, and resembles some forms of X-linked amelogenesis imperfecta in humans. Analysis of the enamel from the Arhgap 6/Amel X-deleted mice verifies that the Amel X gene is nested within the murine Arhgap 6 gene and shows that removal of the entire Amel X gene leads to a phenotype similar to the earlier Amel X null mouse results, in which no amelogenin protein was detected. However, an unusual layer of aprismatic enamel covers the enamel surface, which may be related to the 1.1-Mb deletion, which included Arhgap 6 in these mice.
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Proteínas do Esmalte Dentário/genética , Esmalte Dentário/patologia , Proteínas Ativadoras de GTPase/genética , Deleção de Genes , Camundongos Transgênicos/genética , Amelogênese Imperfeita/genética , Amelogenina , Animais , Modelos Animais de Doenças , Feminino , Humanos , Masculino , Camundongos , Microscopia Eletrônica de Varredura , Microscopia Eletrônica de Transmissão , Fenótipo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Dente/metabolismo , Dente/ultraestruturaRESUMO
Midrapidity open charm spectra from direct reconstruction of D0(D0)-->K-/+pi+/- in d+Au collisions and indirect electron-positron measurements via charm semileptonic decays in p+p and d+Au collisions at squareroot[sNN]=200 GeV are reported. The D0(D0) spectrum covers a transverse momentum (pT) range of 0.1
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Measurements of the production of forward high-energy pi(0) mesons from transversely polarized proton collisions at sqrt[s]=200 GeV are reported. The cross section is generally consistent with next-to-leading order perturbative QCD calculations. The analyzing power is small at x(F) below about 0.3, and becomes positive and large at higher x(F), similar to the trend in data at sqrt[s]< or =20 GeV. The analyzing power is in qualitative agreement with perturbative QCD model expectations. This is the first significant spin result seen for particles produced with p(T)>1 GeV/c at a polarized proton collider.
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The transverse mass spectra and midrapidity yields for Xis and Omegas are presented. For the 10% most central collisions, the (-)Xi(+)/h(-) ratio increases from the Super Proton Synchrotron to the Relativistic Heavy Ion Collider energies while the Xi(-)/h(-) stays approximately constant. A hydrodynamically inspired model fit to the Xi spectra, which assumes a thermalized source, seems to indicate that these multistrange particles experience a significant transverse flow effect, but are emitted when the system is hotter and the flow is smaller than values obtained from a combined fit to pi, K, p, and Lambdas.
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Transverse mass and rapidity distributions for charged pions, charged kaons, protons, and antiprotons are reported for square root of [sNN]=200 GeV pp and Au+Au collisions at Relativistic Heary Ion Collider (RHIC). Chemical and kinetic equilibrium model fits to our data reveal strong radial flow and long duration from chemical to kinetic freeze-out in central Au+Au collisions. The chemical freeze-out temperature appears to be independent of initial conditions at RHIC energies.
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We report results on rho(770)(0)-->pi(+)pi(-) production at midrapidity in p+p and peripheral Au+Au collisions at sqrt[s(NN)]=200 GeV. This is the first direct measurement of rho(770)(0)-->pi(+)pi(-) in heavy-ion collisions. The measured rho(0) peak in the invariant mass distribution is shifted by approximately 40 MeV/c(2) in minimum bias p+p interactions and approximately 70 MeV/c(2) in peripheral Au+Au collisions. The rho(0) mass shift is dependent on transverse momentum and multiplicity. The modification of the rho(0) meson mass, width, and shape due to phase space and dynamical effects are discussed.
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We report the first observations of the first harmonic (directed flow, v(1)) and the fourth harmonic (v(4)), in the azimuthal distribution of particles with respect to the reaction plane in Au+Au collisions at the BNL Relativistic Heavy Ion Collider (RHIC). Both measurements were done taking advantage of the large elliptic flow (v(2)) generated at RHIC. From the correlation of v(2) with v(1) it is determined that v(2) is positive, or in-plane. The integrated v(4) is about a factor of 10 smaller than v(2). For the sixth (v(6)) and eighth (v(8)) harmonics upper limits on the magnitudes are reported.
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We present STAR measurements of the azimuthal anisotropy parameter v(2) and the binary-collision scaled centrality ratio R(CP) for kaons and lambdas (Lambda+Lambda) at midrapidity in Au+Au collisions at square root of s(NN)=200 GeV. In combination, the v(2) and R(CP) particle-type dependencies contradict expectations from partonic energy loss followed by standard fragmentation in vacuum. We establish p(T) approximately 5 GeV/c as the value where the centrality dependent baryon enhancement ends. The K(0)(S) and Lambda+Lambda v(2) values are consistent with expectations of constituent-quark-number scaling from models of hadron formation by parton coalescence or recombination.
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Results on high transverse momentum charged particle emission with respect to the reaction plane are presented for Au + Au collisions at square root s(NN)=200 GeV. Two- and four-particle correlations results are presented as well as a comparison of azimuthal correlations in Au + Au collisions to those in p + p at the same energy. The elliptic anisotropy v(2) is found to reach its maximum at p(t) approximately 3 GeV/c, then decrease slowly and remain significant up to p(t) approximately 7-10 GeV/c. Stronger suppression is found in the back-to-back high-p(t) particle correlations for particles emitted out of plane compared to those emitted in plane. The centrality dependence of v(2) at intermediate p(t) is compared to simple models based on jet quenching.
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We report high statistics measurements of inclusive charged hadron production in Au+Au and p+p collisions at sqrt[s(NN)]=200 GeV. A large, approximately constant hadron suppression is observed in central Au+Au collisions for 5
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We report measurements of single-particle inclusive spectra and two-particle azimuthal distributions of charged hadrons at high transverse momentum (high p(T)) in minimum bias and central d+Au collisions at sqrt[s(NN)]=200 GeV. The inclusive yield is enhanced in d+Au collisions relative to binary-scaled p+p collisions, while the two-particle azimuthal distributions are very similar to those observed in p+p collisions. These results demonstrate that the strong suppression of the inclusive yield and back-to-back correlations at high p(T) previously observed in central Au+Au collisions are due to final-state interactions with the dense medium generated in such collisions.
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The balance function is a new observable based on the principle that charge is locally conserved when particles are pair produced. Balance functions have been measured for charged particle pairs and identified charged pion pairs in Au+Au collisions at the square root of SNN = 130 GeV at the Relativistic Heavy Ion Collider using STAR. Balance functions for peripheral collisions have widths consistent with model predictions based on a superposition of nucleon-nucleon scattering. Widths in central collisions are smaller, consistent with trends predicted by models incorporating late hadronization.
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Azimuthal correlations for large transverse momentum charged hadrons have been measured over a wide pseudorapidity range and full azimuth in Au+Au and p+p collisions at sqrt[s(NN)]=200 GeV. The small-angle correlations observed in p+p collisions and at all centralities of Au+Au collisions are characteristic of hard-scattering processes previously observed in high-energy collisions. A strong back-to-back correlation exists for p+p and peripheral Au+Au. In contrast, the back-to-back correlations are reduced considerably in the most central Au+Au collisions, indicating substantial interaction as the hard-scattered partons or their fragmentation products traverse the medium.
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Azimuthal anisotropy (v(2)) and two-particle angular correlations of high p(T) charged hadrons have been measured in Au+Au collisions at sqrt[s(NN)]=130 GeV for transverse momenta up to 6 GeV/c, where hard processes are expected to contribute significantly. The two-particle angular correlations exhibit elliptic flow and a structure suggestive of fragmentation of high p(T) partons. The monotonic rise of v(2)(p(T)) for p(T)<2 GeV/c is consistent with collective hydrodynamical flow calculations. At p(T)>3 GeV/c, a saturation of v(2) is observed which persists up to p(T)=6 GeV/c.
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Data from the first physics run at the Relativistic Heavy-Ion Collider at Brookhaven National Laboratory, Au+Au collisions at sqrt[s(NN)]=130 GeV, have been analyzed by the STAR Collaboration using three-pion correlations with charged pions to study whether pions are emitted independently at freeze-out. We have made a high-statistics measurement of the three-pion correlation function and calculated the normalized three-particle correlator to obtain a quantitative measurement of the degree of chaoticity of the pion source. It is found that the degree of chaoticity seems to increase with increasing particle multiplicity.