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

Entropically-driven binding of mithramycin in the minor groove of C/G-rich DNA sequences

Final full-text version available at: http://dx.doi.org/10.1093/nar/gkm037.-- Supplementary Data is available.The antitumour antibiotic mithramycin A (MTA) is a DNA minor-groove binding ligand. It binds to C/G-rich tracts as a dimer that forms in the presence of divalent cations such as Mg2+. Differential scanning calorimetry, UV thermal denaturation, isothermal titration calorimetry and competition dialysis were used, together with computations of the hydrophobic free energy of binding, to determine the thermodynamic profile of MTA binding to DNA. The results were compared to those obtained in parallel using the structurally related mithramycin SK (MSK). The binding of MTA to salmon testes DNA determined by UV melting studies (Kobs = 1.2 (±0.3) x 10^5 M–1) is tighter than that of MSK (2.9 (±1.0) x 10^4 M–1) at 25°C. Competition dialysis studies showed a tighter MTA binding to both salmon testes DNA (42% C + G) and Micrococcus lysodeikticus DNA (72% C + G). The thermodynamic analysis of binding data at 25°C shows that the binding of MTA and MSK to DNA is entropically driven, dominated by the hydrophobic transfer of the antibiotics from solution to the DNA-binding site. Direct molecular recognition between MTA or MSK and DNA through hydrogen bonding and van der Waals contacts may also contribute significantly to complex formation.Supported by a grant from the Spanish Ministry of Education and Science (SAF2005-00551) and the FEDER program of the European Community. This work was carried out within the framework of the Centre de Referencia en Biotecnologia of the Generalitat de Catalunya. Funding to pay the Open Access publication charge was provided by the Ministry of Education and Science and CSIC (Spain).Peer reviewe

Analogs of the Catechol Derivative Dynasore Inhibit HIV-1 Ribonuclease H, SARS-CoV-2 nsp14 Exoribonuclease, and Virus Replication

Viral replication often depends on RNA maturation and degradation processes catalyzed by viral ribonucleases, which are therefore candidate targets for antiviral drugs. Here, we synthesized and studied the antiviral properties of a novel nitrocatechol compound (1c) and other analogs that are structurally related to the catechol derivative dynasore. Interestingly, compound 1c strongly inhibited two DEDD box viral ribonucleases, HIV-1 RNase H and SARS-CoV-2 nsp14 3′-to-5′ exoribonuclease (ExoN). While 1c inhibited SARS-CoV-2 ExoN activity, it did not interfere with the mRNA methyltransferase activity of nsp14. In silico molecular docking placed compound 1c in the catalytic pocket of the ExoN domain of nsp14. Finally, 1c inhibited SARS-CoV-2 replication but had no toxicity to human lung adenocarcinoma cells. Given its simple chemical synthesis from easily available starting materials, these results suggest that 1c might be a lead compound for the design of new antiviral compounds that target coronavirus nsp14 ExoN and other viral ribonucleases

Critical Currents, Pinning Forces and Irreversibility Fields in (YxTml-x)Ba2Cu3O7 Single Crystals with Columnar Defects in Fields up to 50 T

We have studied the influence of columnar defects, created by heavy-ion (Kr) irradiation with doses up to 6 10^11 Kr-ions/cm2, on the superconducting critical parameters of single crystalline (YxTm1-x)Ba2Cu3O7. Magnetisation measurements in pulsed fields up to 50 T in the temperature range 4.2 - 90 K revealed that: (i) in fields up to T the critical current Jc(H,T) is considerably enhanced and (ii) down to temperatures T ~ 40 K the irreversibility field Hirr(T) is strongly increased. The field range and magnitude of the Jc(H,T) and Hirr(T) enhancement increase with increasing irradiation dose. To interpret these observations, an effective matching field was defined. Moreover, introducing columnar defects also changes the pinning force fp qualitatively. Due to stronger pinning of flux lines by the amorphous defects, the superconducting critical parameters largely exceed those associated with the defect structures in the unirradiated as-grown material: Jc,irrad(77 K, 5 T) ^3 10* Jc,ref(77 K, 5 T).Comment: 11 pages, all PDF, contribution to Physica

Evidence of Josephson-coupled superconducting regions at the interfaces of Highly Oriented Pyrolytic Graphite

Transport properties of a few hundreds of nanometers thick (in the graphene plane direction) lamellae of highly oriented pyrolytic graphite (HOPG) have been investigated. Current-Voltage characteristics as well as the temperature dependence of the voltage at different fixed input currents provide evidence for Josephson-coupled superconducting regions embedded in the internal two-dimensional interfaces, reaching zero resistance at low enough temperatures. The overall behavior indicates the existence of superconducting regions with critical temperatures above 100 K at the internal interfaces of oriented pyrolytic graphite.Comment: 6 Figures, 5 page

The 21Na(p,gamma)22Mg Reaction and Oxygen-Neon Novae

The 21Na(p,gamma)22Mg reaction is expected to play an important role in the nucleosynthesis of 22Na in Oxygen-Neon novae. The decay of 22Na leads to the emission of a characteristic 1.275 MeV gamma-ray line. This report provides the first direct measurement of the rate of this reaction using a radioactive 21Na beam, and discusses its astrophysical implications. The energy of the important state was measured to be E$_{c.m.}$= 205.7 $\pm$ 0.5 keV with a resonance strength $\omega\gamma = 1.03\pm0.16_{stat}\pm0.14_{sys}$ meV.Comment: Accepted for publication in Physical Review Letter

On the optical properties of Ag^{+15} ion-beam irradiated TiO_{2} and SnO_{2} thin films

The effects of 200-MeV Ag^{+15} ion irradiation on the optical properties of TiO_{2} and SnO_{2} thin films prepared by using the RF magnetron sputtering technique were investigated. These films were characterized by using UV-vis spectroscopy, and with increasing irradiation fluence, the transmittance for the TiO_{2} films was observed to increase systematically while that for SnO_{2} was observed to decrease. Absorption spectra of the irradiated samples showed minor changes in the indirect bandgap from 3.44 to 3.59 eV with increasing irradiation fluence for TiO_{2} while significant changes in the direct bandgap from 3.92 to 3.6 eV were observed for SnO_{2}. The observed modifications in the optical properties of both the TiO_{2} and the SnO_{2} systems with irradiation can be attributed to controlled structural disorder/defects in the system.Comment: 6 pages, ICAMD-201

Depth concentrations of deuterium ions implanted into some pure metals and alloys

Pure metals (Cu, Ti, Zr, V, Pd) and diluted Pd-alloys (Pd-Ag, Pd-Pt, Pd-Ru, Pd-Rh) were implanted by 25 keV deuterium ions at fluences in the range (1.2{\div}2.3)x1022 D+/m2. The post-treatment depth distributions of deuterium ions were measured 10 days and three months after the implantation using Elastic Recoil Detection Analysis (ERDA) and Rutherford Backscattering (RBS). Comparison of the obtained results allowed to make conclusions about relative stability of deuterium and hydrogen gases in pure metals and diluted Pd alloys. Very high diffusion rates of implanted deuterium ions from V and Pd pure metals and Pd alloys were observed. Small-angle X-ray scattering revealed formation of nanosized defects in implanted corundum and titanium.Comment: 12 pages, 9 figure

Ion-beam-induced reconstruction of amorphous GaN

Wurtzite GaN can be rendered amorphous by high-dose heavy-ion bombardment. We show here that relatively low-dose reirradiation of such amorphous GaN (a-GaN) with MeV light ions can significantly change some of the physical properties of a-GaN. In particular, light-ion reirradiation of a-GaN results in (i) an increase in material density, (ii) the suppression of complete decomposition during postimplantation annealing, (iii) a significant increase in the values of hardness and Young's modulus, and (iv) an apparent decrease in the absorption of visible light. Transmission electronmicroscopy shows that a-GaN remains completely amorphous after light-ion reirradiation. Therefore, we attribute the above effects of light-ion reirradiation to an ion-beam-induced atomic-level reconstruction of the amorphous phase. Results indicate that electronic energy loss of light ions is responsible for the changes in the mechanical properties and for the suppression of thermally induced decomposition of a-GaN. However, the changes in the density of a-GaN appear to be controlled by the nuclear energy loss of light ions