A method for the dynamic correction of B0-related distortions in single-echo EPI at 7 T

We propose a method to calculate field maps from the phase of each EPI in an fMRI time series. These field maps can be used to correct the corresponding magnitude images for distortion caused by inhomogeneity in the static magnetic field. In contrast to conventional static distortion correction, in which one 'snapshot’ field map is applied to all subsequent fMRI time points, our method also captures dynamic changes to B0which arise due to motion and respiration. The approach is based on the assumption that the non-B0-related contribution to the phase measured by each radio-frequency coil, which is dominated by the coil sensitivity, is stable over time and can therefore be removed to yield a field map from EPI. Our solution addresses imaging with multi-channel coils at ultra-high field (7 T), where phase offsets vary rapidly in space, phase processing is non-trivial and distortions are comparatively large. We propose using dual-echo gradient echo reference scan for the phase offset calculation, which yields estimates with high signal-to-noise ratio. An extrapolation method is proposed which yields reliable estimates for phase offsets even where motion is large and a tailored phase unwrapping procedure for EPI is suggested which gives robust results in regions with disconnected tissue or strong signal decay. Phase offsets are shown to be stable during long measurements (40 min) and for large head motions. The dynamic distortion correction proposed here is found to work accurately in the presence of large motion (up to 8.1°), whereas a conventional method based on single field map fails to correct or even introduces distortions (up to 11.2 mm). Finally, we show that dynamic unwarping increases the temporal stability of EPI in the presence of motion. Our approach can be applied to any EPI measurements without the need for sequence modification

Gamma and beta frequency oscillations in response to novel auditory stimuli: A comparison of human electroencephalogram (EEG) data with in vitro models

Investigations using hippocampal slices maintained in vitro have demonstrated that bursts of oscillatory field potentials in the gamma frequency range (30-80 Hz) are followed by a slower oscillation in the beta 1 range (12-20 Hz). In this study, we demonstrate that a comparable gamma-to-beta transition is seen in the human electroencephalogram (EEG) in response to novel auditory stimuli. Correlations between gamma and beta 1 activity revealed a high degree of interdependence of synchronized oscillations in these bands in the human EEG. Evoked (stimulus-locked) gamma oscillations preceded beta 1 oscillations in response to novel stimuli, suggesting that this may be analogous to the gamma-to-beta shift observed in vitro. Beta 1 oscillations were the earliest discriminatory responses to show enhancement to novel stimuli, preceding changes in the broad-band event-related potential (mismatch negativity). Later peaks of induced beta activity over the parietal cortex were always accompanied by an underlying gamma frequency oscillation as seen in vitro. A further analogy between in vitro and human recordings was that both gamma and beta oscillations habituated markedly after the initial novel stimulus presentation

Designed Azolopyridinium Salts Block Protective Antigen Pores In Vitro and Protect Cells from Anthrax Toxin

Background:Several intracellular acting bacterial protein toxins of the AB-type, which are known to enter cells by endocytosis, are shown to produce channels. This holds true for protective antigen (PA), the binding component of the tripartite anthrax-toxin of Bacillus anthracis. Evidence has been presented that translocation of the enzymatic components of anthrax-toxin across the endosomal membrane of target cells and channel formation by the heptameric/octameric PA63 binding/translocation component are related phenomena. Chloroquine and some 4-aminoquinolones, known as potent drugs against Plasmodium falciparium infection of humans, block efficiently the PA63-channel in a dose dependent way.Methodology/Principal Findings:Here we demonstrate that related positively charged heterocyclic azolopyridinium salts block the PA63-channel in the μM range, when both, inhibitor and PA63 are added to the same side of the membrane, the cis-side, which corresponds to the lumen of acidified endosomal vesicles of target cells. Noise-analysis allowed the study of the kinetics of the plug formation by the heterocycles. In vivo experiments using J774A.1 macrophages demonstrated that the inhibitors of PA63-channel function also efficiently block intoxication of the cells by the combination lethal factor and PA63 in the same concentration range as they block the channels in vitro.Conclusions/Significance:These results strongly argue in favor of a transport of lethal factor through the PA63-channel and suggest that the heterocycles used in this study could represent attractive candidates for development of novel therapeutic strategies against anthrax. © 2013 Beitzinger et al

Comparative morphological trade-offs between pre- and post-copulatory sexual selection in Giant hissing cockroaches (Tribe: Gromphadorhini)

Sperm competition theory predicts that animals face a trade-off between investment in weaponry and investment in ejaculate composition. Within the Madagascan giant hissing cockroaches (Tribe Gromphadorhini) differences in morphology exist that may indicate differing strategies of male-male competition. We compared relative pronotal horn length using high-resolution X-ray CT scanning data, relative testes mass, and male-male agonistic behaviour between two species of hissing cockroaches, Gromphadorhina oblongonota and Aeluropoda insignis. The gross morphology and behaviour of these two species indicated that G. oblongonota is selected for pre-copulatory mate acquisition and that A. insignis is selected for post-copulatory sperm competition. We found evidence for a trade-off when investing in testes mass vs. horn length between the species. The large, aggressive G. oblongonota follows a strategy of greater investment in weapons at the expense of testes mass while the smaller, less-aggressive A. insignis invests in relatively greater testes mass and less in pronotal weapon length. We also found evidence of a trade-off within each species, where individuals invest more heavily in weapon length at the expense of testes mass. These findings support the predictions of pre- and postcopulatory competitive investment trade-offs for a relatively understudied Tribe of cockroaches

Tailored ß-Cyclodextrin Blocks the Translocation Pores of Binary Exotoxins from C. Botulinum and C. Perfringens and Protects Cells from Intoxication

International audienceBackgroundClostridium botulinum C2 toxin and Clostridium perfringens iota toxin are binary exotoxins, which ADP-ribosylate actin in the cytosol of mammalian cells and thereby destroy the cytoskeleton. C2 and iota toxin consists of two individual proteins, an enzymatic active (A-) component and a separate receptor binding and translocation (B-) component. The latter forms a complex with the A-component on the surface of target cells and after receptor-mediated endocytosis, it mediates the translocation of the A-component from acidified endosomal vesicles into the cytosol. To this end, the B-components form heptameric pores in endosomal membranes, which serve as translocation channels for the A-components.Here we demonstrate that a 7-fold symmetrical positively charged ß-cyclodextrin derivative, per-6-S-(3-aminomethyl)benzylthio-ß-cyclodextrin, protects cultured cells from intoxication with C2 and iota toxins in a concentration-dependent manner starting at low micromolar concentrations. We discovered that the compound inhibited the pH-dependent membrane translocation of the A-components of both toxins in intact cells. Consistently, the compound strongly blocked transmembrane channels formed by the B-components of C2 and iota toxin in planar lipid bilayers in vitro. With C2 toxin, we consecutively ruled out all other possible inhibitory mechanisms showing that the compound did not interfere with the binding of the toxin to the cells or with the enzyme activity of the A-component.Conclusions/SignificanceThe described ß-cyclodextrin derivative was previously identified as one of the most potent inhibitors of the binary lethal toxin of Bacillus anthracis both in vitro and in vivo, implying that it might represent a broad-spectrum inhibitor of binary pore-forming exotoxins from pathogenic bacteria

Self-assembly and anti-amyloid cytotoxicity activity of amyloid beta peptide derivatives

The self-assembly of two derivatives of KLVFF, a fragment Abeta(16-20) of the amyloid beta (Abeta) peptide, is investigated and recovery of viability of neuroblastoma cells exposed to Abeta is observed at sub-stoichiometric peptide concentrations. Fluorescence assays show that NH2-KLVFF-CONH2 undergoes hydrophobic collapse and amyloid formation at the same critical aggregation concentration (cac). In contrast, NH2-K(Boc)LVFF-CONH2 undergoes hydrophobic collapse at a low concentration, followed by amyloid formation at a higher cac. These findings are supported by the beta-sheet features observed by FTIR. Electrospray ionization mass spectrometry indicates that NH2-K(Boc)LVFF-CONH2 forms a significant population of oligomeric species above the cac. Cryo-TEM, used together with SAXS to determine fibril dimensions, shows that the length and degree of twisting of peptide fibrils seem to be influenced by the net peptide charge. Grazing incidence X-ray scattering from thin peptide films shows features of beta-sheet ordering for both peptides, along with evidence for lamellar ordering of NH2-KLVFF-CONH2. This work provides a comprehensive picture of the aggregation properties of these two KLVFF derivatives and show their utility, in unaggregated form, in restoring the viability of neuroblastoma cells against Abeta-induced toxicity

f(R) theories

Over the past decade, f(R) theories have been extensively studied as one of the simplest modifications to General Relativity. In this article we review various applications of f(R) theories to cosmology and gravity - such as inflation, dark energy, local gravity constraints, cosmological perturbations, and spherically symmetric solutions in weak and strong gravitational backgrounds. We present a number of ways to distinguish those theories from General Relativity observationally and experimentally. We also discuss the extension to other modified gravity theories such as Brans-Dicke theory and Gauss-Bonnet gravity, and address models that can satisfy both cosmological and local gravity constraints.Comment: 156 pages, 14 figures, Invited review article in Living Reviews in Relativity, Published version, Comments are welcom

Performance of CMS muon reconstruction in pp collision events at sqrt(s) = 7 TeV

The performance of muon reconstruction, identification, and triggering in CMS has been studied using 40 inverse picobarns of data collected in pp collisions at sqrt(s) = 7 TeV at the LHC in 2010. A few benchmark sets of selection criteria covering a wide range of physics analysis needs have been examined. For all considered selections, the efficiency to reconstruct and identify a muon with a transverse momentum pT larger than a few GeV is above 95% over the whole region of pseudorapidity covered by the CMS muon system, abs(eta) < 2.4, while the probability to misidentify a hadron as a muon is well below 1%. The efficiency to trigger on single muons with pT above a few GeV is higher than 90% over the full eta range, and typically substantially better. The overall momentum scale is measured to a precision of 0.2% with muons from Z decays. The transverse momentum resolution varies from 1% to 6% depending on pseudorapidity for muons with pT below 100 GeV and, using cosmic rays, it is shown to be better than 10% in the central region up to pT = 1 TeV. Observed distributions of all quantities are well reproduced by the Monte Carlo simulation.Comment: Replaced with published version. Added journal reference and DO

Performance of CMS muon reconstruction in pp collision events at sqrt(s) = 7 TeV

The performance of muon reconstruction, identification, and triggering in CMS has been studied using 40 inverse picobarns of data collected in pp collisions at sqrt(s) = 7 TeV at the LHC in 2010. A few benchmark sets of selection criteria covering a wide range of physics analysis needs have been examined. For all considered selections, the efficiency to reconstruct and identify a muon with a transverse momentum pT larger than a few GeV is above 95% over the whole region of pseudorapidity covered by the CMS muon system, abs(eta) < 2.4, while the probability to misidentify a hadron as a muon is well below 1%. The efficiency to trigger on single muons with pT above a few GeV is higher than 90% over the full eta range, and typically substantially better. The overall momentum scale is measured to a precision of 0.2% with muons from Z decays. The transverse momentum resolution varies from 1% to 6% depending on pseudorapidity for muons with pT below 100 GeV and, using cosmic rays, it is shown to be better than 10% in the central region up to pT = 1 TeV. Observed distributions of all quantities are well reproduced by the Monte Carlo simulation.Comment: Replaced with published version. Added journal reference and DO

X-ray emission from the Sombrero galaxy: discrete sources

We present a study of discrete X-ray sources in and around the bulge-dominated, massive Sa galaxy, Sombrero (M104), based on new and archival Chandra observations with a total exposure of ~200 ks. With a detection limit of L_X = 1E37 erg/s and a field of view covering a galactocentric radius of ~30 kpc (11.5 arcminute), 383 sources are detected. Cross-correlation with Spitler et al.'s catalogue of Sombrero globular clusters (GCs) identified from HST/ACS observations reveals 41 X-rays sources in GCs, presumably low-mass X-ray binaries (LMXBs). We quantify the differential luminosity functions (LFs) for both the detected GC and field LMXBs, whose power-low indices (~1.1 for the GC-LF and ~1.6 for field-LF) are consistent with previous studies for elliptical galaxies. With precise sky positions of the GCs without a detected X-ray source, we further quantify, through a fluctuation analysis, the GC LF at fainter luminosities down to 1E35 erg/s. The derived index rules out a faint-end slope flatter than 1.1 at a 2 sigma significance, contrary to recent findings in several elliptical galaxies and the bulge of M31. On the other hand, the 2-6 keV unresolved emission places a tight constraint on the field LF, implying a flattened index of ~1.0 below 1E37 erg/s. We also detect 101 sources in the halo of Sombrero. The presence of these sources cannot be interpreted as galactic LMXBs whose spatial distribution empirically follows the starlight. Their number is also higher than the expected number of cosmic AGNs (52+/-11 [1 sigma]) whose surface density is constrained by deep X-ray surveys. We suggest that either the cosmic X-ray background is unusually high in the direction of Sombrero, or a distinct population of X-ray sources is present in the halo of Sombrero.Comment: 11 figures, 5 tables, ApJ in pres