Pathological regional blood flow in opiate-dependent patients during withdrawal: A HMPAO-SPECT study

The aims of the present study were to investigate regional cerebral blood flow (rCBF) in heroin-dependent patients during withdrawal and to assess the relation between these changes and duration of heroin consumption and withdrawal data. The rCBF was measured using brain SPECT with Tc-99m-HMPAO in 16 heroin-dependent patients during heroin withdrawal. Thirteen patients received levomethadone at the time of the SPECT scans. The images were analyzed both visually and quantitatively, a total of 21 hypoperfused brain regions were observed in 11 of the 16 patients. The temporal lobes were the most affected area, hypoperfusions of the right and left temporal lobe were observed in 5 and 5 patients, respectively. Three of the patients had a hypoperfusion of the right frontal lobe, 2 patients showed perfusion defects in the left frontal lobe, right parietal lobe and left parietal lobe. The results of the quantitative assessments of the rCBF were consistent with the results of the qualitative findings. The stepwise regression analysis showed a significant positive correlation (r = 0.54) between the dose of levomethadone at the time of the SPECT scan and the rCBF of the right parietal lobe. Other significant correlations between clinical data and rCBF were not found. The present results suggest brain perfusion abnormalities during heroin withdrawal in heroin-dependent patients, which are not due to the conditions of withdrawal

Coherent Versus Incoherent Ladar Detection at 2.09 μm

A 2.09-μm ladar system is built to compare coherent to incoherent detection. The 2.09-μm wavelength is of interest because of its high atmospheric transmission and because it is eyesafe. The 2.09-μm system presented is capable of either a coherent or incoherent operational mode, is tunable in a small region around 2.09 μm, and is being used to look at the statistical nature of the ladar return pulses for typical glint and speckle targets. To compare coherent to incoherent detection the probability of detection is investigated as the primary performance criterion of interest. The probability of detection is dependent on both the probability of false alarm and the probability density function, representing the signal current output from the detector. These probability distributions are different for each detection technique and for each type of target. Furthermore, the probability of detection and the probability of false alarm are both functions of the dominating noise source(s) in the system. A description of the theoretical expectations of this system along with the setup of the ladar system and how it is being used to collect data for both coherent and incoherent detection is presented

Variations of the McEliece Cryptosystem

Two variations of the McEliece cryptosystem are presented. The first one is based on a relaxation of the column permutation in the classical McEliece scrambling process. This is done in such a way that the Hamming weight of the error, added in the encryption process, can be controlled so that efficient decryption remains possible. The second variation is based on the use of spatially coupled moderate-density parity-check codes as secret codes. These codes are known for their excellent error-correction performance and allow for a relatively low key size in the cryptosystem. For both variants the security with respect to known attacks is discussed

Observation of conformational changes that underlie the catalytic cycle of Xrn2

Nuclear magnetic resonance (NMR) methods that quantitatively probe motions on molecular and atomic levels have propelled the understanding of biomolecular processes for which static structures cannot provide a satisfactory description. In this work, we studied the structure and dynamics of the essential 100-kDa eukaryotic 5′→3′ exoribonuclease Xrn2. A combination of complementary fluorine and methyl-TROSY NMR spectroscopy reveals that the apo enzyme is highly dynamic around the catalytic center. These observed dynamics are in agreement with a transition of the enzyme from the ground state into a catalytically competent state. We show that the conformational equilibrium in Xrn2 shifts substantially toward the active state in the presence of substrate and magnesium. Finally, our data reveal that the dynamics in Xrn2 correlate with the RNA degradation rate, as a mutation that attenuates motions also affects catalytic activity. In that light, our results stress the importance of studies that go beyond static structural information

Multi‐Site Conformational Exchange in the Synthetic Neomycin‐Sensing Riboswitch Studied by 19 F NMR

The synthetic neomycin-sensing riboswitch interacts with its cognate ligand neomycin as well as with the related antibiotics ribostamycin and paromomycin. Binding of these aminoglycosides induces a very similar ground state structure in the RNA, however, only neomycin can efficiently repress translation initiation. The molecular origin of these differences has been traced back to differences in the dynamics of the ligand:riboswitch complexes. Here, we combine five complementary fluorine based NMR methods to accurately quantify seconds to microseconds dynamics in the three riboswitch complexes. Our data reveal complex exchange processes with up to four structurally different states. We interpret our findings in a model that shows an interplay between different chemical groups in the antibiotics and specific bases in the riboswitch. More generally, our data underscore the potential of 19F NMR methods to characterize complex exchange processes with multiple excited states

Common variants in FOXP1 are associated with generalized vitiligo

In a recent genome-wide association study of generalized vitiligo, we identified ten confirmed susceptibility loci. By testing additional loci that showed suggestive association in the genome-wide study, using two replication cohorts of European descent, we observed replicated association of generalized vitiligo with variants at 3p13 encompassing FOXP1 (rs17008723, combined P = 1.04 × 10−8) and with variants at 6q27 encompassing CCR6 (rs6902119, combined P = 3.94 × 10−7)

¹⁹F NMR Untersuchung des Konformationsaustauschs mehrerer Zustände im synthetischen Neomycin‐bindenden Riboschalter

Der synthetische Neomycin-bindende Riboschalter interagiert mit seinem Liganden Neomycin sowie mit den verwandten Antibiotika Ribostamycin und Paromomycin. Die Bindung dieser Aminoglykoside induziert sehr ähnliche Grundzustandsstrukturen in der RNA, allerdings kann nur Neomycin die Initiierung der Translation effizient unterdrücken. Der molekulare Ursprung dieser Unterschiede wurde auf Unterschiede in der Dynamik der Ligand-Riboschalter-Komplexe zurückgeführt. In diesem Artikel kombinieren wir fünf komplementäre fluorbasierte NMR-Methoden, um die Dynamik der drei Riboschalter-Komplexe im Sekunden- bis Mikrosekundenbereich genau zu quantifizieren. Unsere Daten offenbaren komplexe Austauschprozesse mit bis zu vier strukturell unterschiedlichen Zuständen. Wir interpretieren unsere Ergebnisse in einem Modell, das ein Zusammenspiel zwischen verschiedenen chemischen Gruppen in den Antibiotika und spezifischen Basen im Riboschalter zeigt. Allgemeiner unterstreichen unsere Daten das Potenzial von 19F NMR-Methoden, komplexe Austauschprozesse mit mehreren angeregten Zuständen zu charakterisieren

Long-term spectral and timing properties of the soft gamma-ray repeater SGR 1833-0832 and detection of extended X-ray emission around the radio pulsar PSR B1830-08

SGR 1833-0832 was discovered on 2010 March 19 thanks to the Swift detection of a short hard X-ray burst and follow-up X-ray observations. Since then, it was repeatedly observed with Swift, Rossi X-ray Timing Explorer, and XMM-Newton. Using these data, which span about 225 days, we studied the long-term spectral and timing characteristics of SGR 1833-0832. We found evidence for diffuse emission surrounding SGR 1833-0832, which is most likely a halo produced by the scattering of the point source X-ray radiation by dust along the line of sight, and we show that the source X-ray spectrum is well described by an absorbed blackbody, with temperature kT=1.2 keV and absorbing column nH=(10.4+/-0.2)E22 cm^-2, while different or more complex models are disfavoured. The source persistent X-ray emission remained fairly constant at about 3.7E-12 erg/cm^2/s for the first 20 days after the onset of the bursting episode, then it faded by a factor 40 in the subsequent 140 days, following a power-law trend with index alpha=-0.5. We obtained a phase-coherent timing solution with the longest baseline (225 days) to date for this source which, besides period P=7.5654084(4) s and period derivative dP/dt=3.5(3)E-12 s/s, includes higher order period derivatives. We also report on our search of the counterpart to the SGR at radio frequencies using the Australia Telescope Compact Array and the Parkes radio telescope. No evidence for radio emission was found, down to flux densities of 0.9 mJy (at 1.5 GHz) and 0.09 mJy (at 1.4 GHz) for the continuum and pulsed emissions, respectively, consistently with other observations at different epochs.Comment: 12 pages, 7 colour figures and 3 tables, accepted for publication in MNRAS. Figure 6 in reduced quality and abstract abridged for astro-ph submissio

Tunable quantum dots from atomically precise graphene nanoribbons using a multi-gate architecture

Atomically precise graphene nanoribbons (GNRs) are increasingly attracting interest due to their largely modifiable electronic properties, which can be tailored by controlling their width and edge structure during chemical synthesis. In recent years, the exploitation of GNR properties for electronic devices has focused on GNR integration into field-effect-transistor (FET) geometries. However, such FET devices have limited electrostatic tunability due to the presence of a single gate. Here, we report on the device integration of 9-atom wide armchair graphene nanoribbons (9-AGNRs) into a multi-gate FET geometry, consisting of an ultra-narrow finger gate and two side gates. We use high-resolution electron-beam lithography (EBL) for defining finger gates as narrow as 12 nm and combine them with graphene electrodes for contacting the GNRs. Low-temperature transport spectroscopy measurements reveal quantum dot (QD) behavior with rich Coulomb diamond patterns, suggesting that the GNRs form QDs that are connected both in series and in parallel. Moreover, we show that the additional gates enable differential tuning of the QDs in the nanojunction, providing the first step towards multi-gate control of GNR-based multi-dot systems