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Background: High baseline levels of IP-10 predict a slower first phase decline in HCV RNA and a poor outcome following interferon/ribavirin therapy in patients with chronic hepatitis C. Several recent studies report that single nucleotide polymorphisms (SNPs) adjacent to IL28B predict spontaneous resolution of HCV infection and outcome of treatment among HCV genotype 1 infected patients. Methods and Findings: In the present study, we correlated the occurrence of variants at three such SNPs (rs12979860, rs12980275, and rs8099917) with pretreatment plasma IP-10 and HCV RNA throughout therapy within a phase III treatment trial (HCV-DITTO) involving 253 Caucasian patients. The favorable SNP variants (CC, AA, and TT, respectively) were associated with lower baseline IP-10 (P = 0.02, P = 0.01, P = 0.04) and were less common among HCV genotype 1 infected patients than genotype 2/3 (P<0.0001, P<0.0001, and P = 0.01). Patients carrying favorable SNP genotypes had higher baseline viral load than those carrying unfavorable variants (P = 0.0013, P = 0.029, P = 0.0004 respectively). Among HCV genotype 1 infected carriers of the favorable C, A, or T alleles, IP-10 below 150 pg/mL significantly predicted a more pronounced reduction of HCV RNA from day 0 to 4 (first phase decline), which translated into increased rates of RVR (62%, 53%, and 39%) and SVR (85%, 76%, and 75% respectively) among homozygous carriers with baseline IP-10 below 150 pg/mL. In multivariate analyses of genotype 1-infected patients, baseline IP-10 and C genotype at rs12979860 independently predicted the first phase viral decline and RVR, which in turn independently predicted SVR. Conclusions: Concomitant assessment of pretreatment IP-10 and IL28B-related SNPs augments the prediction of the first phase decline in HCV RNA, RVR, and final therapeutic outcome.
We present the first measurement of fluctuations from event to event in the production of strange particles in collisions of heavy nuclei. The ratio of charged kaons to charged pions is determined for individual central Pb+Pb collisions. After accounting for the fluctuations due to detector resolution and finite number statistics we derive an upper limit on genuine non-statistical fluctuations, perhaps related to a first or second order QCD phase transition. Such fluctuations are shown to be very small.
Results are presented from a search for the decays D0 -> K min pi plus and D0 bar -> K plus pi min in a sample of 3.8x10^6 central Pb-Pb events collected with a beam energy of 158A GeV by NA49 at the CERN SPS. No signal is observed. An upper limit on D0 production is derived and compared to predictions from several models.
Directed and elliptic flow of charged pions and protons in Pb + Pb collisions at 40 and 158 A GeV
(2003)
Directed and elliptic flow measurements for charged pions and protons are reported as a function of transverse momentum, rapidity, and centrality for 40 and 158A GeV Pb + Pb collisions as recorded by the NA49 detector. Both the standard method of correlating particles with an event plane, and the cumulant method of studying multiparticle correlations are used. In the standard method the directed flow is corrected for conservation of momentum. In the cumulant method elliptic flow is reconstructed from genuine 4, 6, and 8-particle correlations, showing the first unequivocal evidence for collective motion in A+A collisions at SPS energies.
Background: Interferon and ribavirin therapy for chronic hepatitis C virus (HCV) infection yields sustained virological response (SVR) rates of 50–80%. Several factors such as non-1 genotype, beneficial IL28B genetic variants, low baseline IP-10, and the functionality of HCV-specific T cells predict SVR. With the pending introduction of new therapies for HCV entailing very rapid clearance of plasma HCV RNA, the importance of baseline biomarkers likely will increase in order to tailor therapy. CD26 (DPPIV) truncates the chemokine IP-10 into a shorter antagonistic form, and this truncation of IP-10 has been suggested to influence treatment outcome in patients with chronic HCV infection patients. In addition, previous reports have shown CD26 to be a co-stimulator for T cells. The aim of the present study was to assess the utility of CD26 as a biomarker for treatment outcome in chronic hepatitis C and to define its association with HCV-specific T cells.
Methods: Baseline plasma from 153 genotype 1 and 58 genotype 2/3 infected patients enrolled in an international multicenter phase III trial (DITTO-HCV) and 36 genotype 1 infected patients participating in a Swedish trial (TTG1) were evaluated regarding baseline soluble CD26 (sCD26) and the functionality of HCV-specific CD8+ T cells.
Results: Genotype 1 infected patients achieving SVR in the DITTO (P = 0.002) and the TTG1 (P = 0.02) studies had lower pretreatment sCD26 concentrations compared with non-SVR patients. Sixty-five percent of patients with sCD26 concentrations below 600 ng/mL achieved SVR compared with 39% of the patients with sCD26 exceeding 600 ng/mL (P = 0.01). Patients with sCD26 concentrations below 600 ng/mL had significantly higher frequencies of HCV-specific CD8+ T cells (P = 0.02).
Conclusions: Low baseline systemic concentrations of sCD26 predict favorable treatment outcome in chronic HCV infection and may be associated with higher blood counts of HCV-specific CD8+ T cells.
In this study, we investigate the interaction of jets with their environment at a microscopic level, which is a key open question in the study of relativistic jets. Using small simulation systems during past research, we initially studied the evolution of both electron–proton and electron–positron relativistic jets containing helical magnetic fields, by focusing on their interactions with an ambient plasma. Here, using larger jet radii, we have performed simulations of global jets containing helical magnetic fields in order to examine how helical magnetic fields affect kinetic instabilities, such as the Weibel instability, the kinetic Kelvin–Helmholtz instability (kKHI) and the mushroom instability (MI). We found that the evolution of global jets strongly depends on the size of the jet radius. For example, phase bunching of jet electrons, in particular in the electron–proton jet, is mixed with a larger jet radius as a result of the more complicated structures of magnetic fields with excited kinetic instabilities. In our simulation, these kinetic instabilities led to new types of instabilities in global jets. In the electron–proton jet simulation, a modified recollimation occurred, and jet electrons were strongly perturbed. In the electron–positron jet simulation, mixed kinetic instabilities occurred early, followed by a turbulence-like structure. Simulations using much larger (and longer) systems are required in order to further thoroughly investigate the evolution of global jets containing helical magnetic fields.
Inositol, 1,2,3,4,5,6-hexahydroxycyclohexane, exists in nine stereoisomers with different crystal structures and melting points. In a previous paper on the relationship between the melting points of the inositols and the hydrogen-bonding patterns in their crystal structures [Simperler et al. (2006[Simperler, A., Watt, S. W., Bonnet, P. A., Jones, W. & Motherwell, W. D. S. (2006). CrystEngComm, 8, 589-600.]). CrystEngComm 8, 589], it was noted that although all inositol crystal structures known at that time contained 12 hydrogen bonds per molecule, their melting points span a large range of about 170 °C. Our preliminary investigations suggested that the highest melting point must be corrected for the effect of molecular symmetry, and that the three lowest melting points may need to be revised. This prompted a full investigation, with additional experiments on six of the nine inositols. Thirteen new phases were discovered; for all of these their crystal structures were examined. The crystal structures of eight ordered phases could be determined, of which seven were obtained from laboratory X-ray powder diffraction data. Five additional phases turned out to be rotator phases and only their unit cells could be determined. Two previously unknown melting points were measured, as well as most enthalpies of melting. Several previously reported melting points were shown to be solid-to-solid phase transitions or decomposition points. Our experiments have revealed a complex picture of phases, rotator phases and phase transitions, in which a simple correlation between melting points and hydrogen-bonding patterns is not feasible.
12 hepatics and 32 mosses are reported new to Uganda, 1 moss being also new to Africa, and 1 liverwort new to mainland Africa. Ectropothecium plumigerum (Broth.) Hedenäs is a new combination (basionym: Isopterygium plumigerum Broth.) with a new synonym Taxicaulis plumirameus Müll.Hal. nom. nud., and Taxiphyllum maniae (Renauld & Paris) M. Fleisch. is a new synonym of Taxiphyllum taxirameum (Mitt.) M.Fleisch. Three mosses are removed from the Uganda list.
The value of plant ecological datasets with hundreds or thousands of species is principally determined by the taxonomic accuracy of their plant names. However, combining existing lists of species to assemble a harmonized dataset that is clean of taxonomic errors can be a difficult task for non-taxonomists. Here, we describe the range of taxonomic difficulties likely to be encountered during dataset assembly and present an easy-to-use taxonomic cleaning protocol aimed at assisting researchers not familiar with the finer details of taxonomic cleaning. The protocol produces a final dataset (FD) linked to a companion dataset (CD), providing clear details of the path from existing lists to the FD taken by each cleaned taxon. Taxa are checked off against ten categories in the CD that succinctly summarize all taxonomic modifications required. Two older, publicly-available lists of naturalized Asteraceae in Australia were merged into a harmonized dataset as a case study to quantify the impacts of ignoring the critical process of taxonomic cleaning in invasion ecology. Our FD of naturalized Asteraceae contained 257 species and infra-species. Without implementation of the full cleaning protocol, the dataset would have contained 328 taxa, a 28% overestimate of taxon richness by 71 taxa. Our naturalized Asteraceae CD described the exclusion of 88 names due to nomenclatural issues (e.g. synonymy), the inclusion of 26 updated currently accepted names and four taxa newly naturalized since the production of the source datasets, and the exclusion of 13 taxa that were either found not to be in Australia or were in fact doubtfully naturalized. This study also supports the notion that automated processes alone will not be enough to ensure taxonomically clean datasets, and that manual scrutiny of data is essential. In the long term, this will best be supported by increased investment in taxonomy and botany in university curricula.
The particle-in-cell (PIC) method was developed to investigate microscopic phenomena, and with the advances in computing power, newly developed codes have been used for several fields, such as astrophysical, magnetospheric, and solar plasmas. PIC applications have grown extensively, with large computing powers available on supercomputers such as Pleiades and Blue Waters in the US. For astrophysical plasma research, PIC methods have been utilized for several topics, such as reconnection, pulsar dynamics, non-relativistic shocks, relativistic shocks, and relativistic jets. PIC simulations of relativistic jets have been reviewed with emphasis placed on the physics involved in the simulations. This review summarizes PIC simulations, starting with the Weibel instability in slab models of jets, and then focuses on global jet evolution in helical magnetic field geometry. In particular, we address kinetic Kelvin-Helmholtz instabilities and mushroom instabilities.