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The lysosomal ABC transporter associated with antigen processing-like (TAPL, ABCB9) acts as an ATP-dependent polypeptide transporter with broad length selectivity. To characterize in detail its substrate specificity, a procedure for functional reconstitution of human TAPL was developed. By intensive screening of detergents, ideal solubilization conditions were evolved with respect to efficiency, long term stability, and functionality of TAPL. TAPL was isolated in a two-step procedure with high purity and, subsequently, reconstituted into proteoliposomes. The peptide transport activity of reconstituted TAPL strongly depends on the lipid composition. With the help of combinatorial peptide libraries, the key positions of the peptides were localized to the N- and C-terminal residues with respect to peptide transport. At both ends, TAPL favors positively charged, aromatic, or hydrophobic residues and disfavors negatively charged residues as well as asparagine and methionine. Besides specific interactions of both terminal residues, electrostatic interactions are important, since peptides with positive net charge are more efficiently transported than negatively charged ones.
The thickness of the cerebral cortex can provide valuable information about normal and abnormal neuroanatomy. High resolution MRI together with powerful image processing techniques has made it possible to perform these measurements automatically over the whole brain. Here we present a method for automatically generating voxel-based cortical thickness (VBCT) maps. This technique results in maps where each voxel in the grey matter is assigned a thickness value. Sub-voxel measurements of thickness are possible using sub-sampling and interpolation of the image information. The method is applied to repeated MRI scans of a single subject from two MRI scanners to demonstrate its robustness and reproducibility. A simulated data set is used to show that small focal differences in thickness between two groups of subjects can be detected. We propose that the analysis of VBCT maps can provide results that are complementary to other anatomical analyses such as voxel-based morphometry.
We present a measurement of e+e− pair production in central PbAu collisions at 158A GeV/c. As reported earlier, a significant excess of the e+e− pair yield over the expectation from hadron decays is observed. The improved mass resolution of the present data set, recorded with the upgraded CERES experiment at the CERN-SPS, allows for a comparison of the data with different theoretical approaches. The data clearly favor a substantial in-medium broadening of the ρ spectral function over a density-dependent shift of the ρ pole mass. The in-medium broadening model implies that baryon induced interactions are the key mechanism to the observed modifications of the ρ meson at SPS energy.
Ribavirin in combination with peginterferon alfa shows strong clinical efficacy against chronic hepatitis C, and is now established as the standard of care. However, the precise role of ribavirin is still being defined, suggesting that optimal ribavirin dose should be maintained over the whole treatment period. Ribavirin dosage varies by bodyweight for genotype 1 disease (1000 mg/day in patients ⩽75 kg and 1200 mg/day in patients >75 kg), whereas 800 mg/day is sufficient to ensure optimal response in all genotype 2/3 patients. Similarly, genotype 1 patients benefit from 48 weeks of therapy, while 24 weeks is sufficient for genotype 2/3 disease.
Recent data suggest treatment success is dependent on cumulative ribavirin exposure, as patients who receive <60% of the planned dose have lower response rates, regardless of whether reductions are from temporary interruptions or premature cessation of therapy. All patients should be monitored for hemolytic anemia, as early diagnosis allows management through small dose reductions and stepwise return to the target dose, maximizing cumulative exposure. Despite these recent advances in our knowledge, many questions remain, such as whether the role of ribavirin will change or even be eliminated as new therapies are developed.
The extrapolation of results obtained on a series of 3 succeeding grids with halved mesh size is tested as a variant of the multigrid approach for solving the Laplace and Poisson equations in 2D. Based on corresponding experience with BEM for electric and magnetic [2] field problems a pure power law is applied instead of the famous Richardson extrapolation [3]. On those grid points, which are common to all 3 grids, the potential values are extrapolated to an arbitrary fine discretization. On the points of the finest grid in between those of the coarser ones the potentials then are obtained by only few iterations to perform the interpolation. Both, the common 5-point discretization and the famous 9-point discretization by E. Kasper [5] are investigated and compared with respect to the possible win of accuracy by extrapolation. As an interesting result of this kind of extrapolation, the accumulated local discretization errors of the 5-point discretization are partially cured and the high accuracy by the 9-point formula of Kasper makes extrapolation inefficient. Like for classical MG (multi grid) [6] the acceleration of potential calculations on grids of large size is substantial.
Mitochondrial complex I (NADH:ubiquinone oxidoreductase) undergoes reversible deactivation upon incubation at 30–37 °C. The active/deactive transition could play an important role in the regulation of complex I activity. It has been suggested recently that complex I may become modified by S-nitrosation under pathological conditions during hypoxia or when the nitric oxide:oxygen ratio increases. Apparently, a specific cysteine becomes accessible to chemical modification only in the deactive form of the enzyme. By selective fluorescence labeling and proteomic analysis, we have identified this residue as cysteine-39 of the mitochondrially encoded ND3 subunit of bovine heart mitochondria. Cysteine-39 is located in a loop connecting the first and second transmembrane helix of this highly hydrophobic subunit. We propose that this loop connects the ND3 subunit of the membrane arm with the PSST subunit of the peripheral arm of complex I, placing it in a region that is known to be critical for the catalytic mechanism of complex I. In fact, mutations in three positions of the loop were previously reported to cause Leigh syndrome with and without dystonia or progressive mitochondrial disease.
Dilepton production in pp and Au+Au nucleus–nucleus collisions at s=200GeV as well as in In+In and Pb+Au at 158AGeV is studied within the microscopic HSD transport approach. A comparison to the data from the PHENIX Collaboration at RHIC shows that standard in-medium effects of the ρ,ω vector mesons—compatible with the NA60 data for In+In at 158AGeV and the CERES data for Pb+Au at 158AGeV—do not explain the large enhancement observed in the invariant mass regime from 0.2 to 0.5 GeV in Au+Au collisions at s=200 GeV relative to pp collisions.
We explore the formation of diquark bound states and their Bose–Einstein condensation (BEC) in the phase diagram of three-flavor quark matter at nonzero temperature, T, and quark chemical potential, μ. Using a quark model with a four-fermion interaction, we identify diquark excitations as poles of the microscopically computed diquark propagator. The quark masses are obtained by solving a dynamical equation for the chiral condensate and are found to determine the stability of the diquark excitations. The stability of diquark excitations is investigated in the T–μ plane for different values of the diquark coupling strength. We find that diquark bound states appear at small quark chemical potentials and at intermediate coupling strengths. Bose–Einstein condensation of non-strange diquark states occurs when the attractive interaction between quarks is sufficiently strong.
We propose that the measurement of the transverse momentum dependence of the double ratio of the nuclear modification factors of charm and bottom jets, RAAc(pT)/RAAb(pT), in central nuclear collisions at the LHC will provide an especially robust observable that can be used to differentiate Standard Model perturbative QCD predictions from recently proposed strong coupling string drag models derived using the AdS/CFT conjecture.