Wide therapeutic time window for nimesulide neuroprotection in a model of transient focal cerebral ischemia in the rat

Results from several studies indicate that cyclooxygenase-2 (COX-2) is involved ischemic brain injury. The purpose of this study was to evaluate the neuroprotective effects of the selective COX-2 inhibitor nimesulide on cerebral infarction and neurological deficits in a standardized model of transient focal cerebral ischemia in rats. Three doses of nimesulide (3, 6 and 12 mg/kg; i.p.) or vehicle were administered immediately after stroke and additional doses were given at 6, 12, 24, 36 and 48 h after ischemia. In other set of experiments, the effect of nimesulide was studied in a situation in which its first administration was delayed for 3 to 24 h after ischemia. Total, cortical and subcortical infarct volumes and functional outcome (assessed by neurological deficit score and rotarod performance) were determined 3 days after ischemia. The effect of nimesulide on prostaglandin E2 (PGE2) levels in the injured brain was also investigated. Nimesulide dose-dependently reduced infarct volume and improved functional recovery when compared to vehicle. Of interest is the finding that neuroprotection conferred by nimesulide (reduction of infarct size and neurological deficits and improvement of rotarod performance) was also observed when treatment was delayed until 24 h after ischemia. Further, administration of nimesulide in a delayed treatment paradigm completely abolished PGE2 accumulation in the postischemic brain, suggesting that COX-2 inhibition is a promising therapeutic strategy for cerebral ischemia to target the late-occurring inflammatory events which amplify initial damage

The low-temperature energy calibration system for the CUORE bolometer array

The CUORE experiment will search for neutrinoless double beta decay (0nDBD) of 130Te using an array of 988 TeO_2 bolometers operated at 10 mK in the Laboratori Nazionali del Gran Sasso (Italy). The detector is housed in a large cryogen-free cryostat cooled by pulse tubes and a high-power dilution refrigerator. The TeO_2 bolometers measure the event energies, and a precise and reliable energy calibration is critical for the successful identification of candidate 0nDBD and background events. The detector calibration system under development is based on the insertion of 12 gamma-sources that are able to move under their own weight through a set of guide tubes that route them from deployment boxes on the 300K flange down into position in the detector region inside the cryostat. The CUORE experiment poses stringent requirements on the maximum heat load on the cryostat, material radiopurity, contamination risk and the ability to fully retract the sources during normal data taking. Together with the integration into a unique cryostat, this requires careful design and unconventional solutions. We present the design, challenges, and expected performance of this low-temperature energy calibration system.Comment: To be published in the proceedings of the 13th International Workshop on Low Temperature Detectors (LTD), Stanford, CA, July 20-24, 200

Development of temporal auditory processing in childhood: Changes in efficiency rather than temporal-modulation selectivity

The ability to detect amplitude modulation (AM) is essential to distinguish the spectro-temporal features of speech from those of a competing masker. Previous work shows that AM sensitivity improves until 10 years of age. This may relate to the development of sensory factors (tuning of AM filters, susceptibility to AM masking) or to changes in processing efficiency (reduction in internal noise, optimization of decision strategies). To disentangle these hypotheses, three groups of children (5–11 years) and one of young adults completed psychophysical tasks measuring thresholds for detecting sinusoidal AM (with a rate of 4, 8, or 32 Hz) applied to carriers whose inherent modulations exerted different amounts of AM masking. Results showed that between 5 and 11 years, AM detection thresholds improved and that susceptibility to AM masking slightly increased. However, the effects of AM rate and carrier were not associated with age, suggesting that sensory factors are mature by 5 years. Subsequent modelling indicated that reducing internal noise by a factor 10 accounted for the observed developmental trends. Finally, children’s consonant identification thresholds in noise related to some extent to AM sensitivity. Increased efficiency in AM detection may support better use of temporal information in speech during childhood

Temporal integration for amplitude modulation in childhood: Interaction between internal noise and memory

It is still unclear whether the gradual improvement in amplitude-modulation (AM) sensitivity typically found in children up to 10 years of age reflects an improvement in “processing efficiency” (the central ability to use information extracted by sensory mechanisms). This hypothesis was tested by evaluating temporal integration for AM, a capacity relying on memory and decision factors. This was achieved by measuring the effect of increasing the number of AM cycles (2 vs 8) on AM-detection thresholds for three groups of children aged from 5 to 11 years and a group of young adults. AM-detection thresholds were measured using a forced-choice procedure and sinusoidal AM (4 or 32 Hz rate) applied to a 1024-Hz pure-tone carrier. All age groups demonstrated temporal integration for AM at both rates; that is, significant improvements in AM sensitivity with a higher number of AM cycles. However, an effect of age is observed as both 5–6 year olds and adults exhibited more temporal integration compared to 7–8 and 10–11 year olds at both rates. This difference is due to: (i) the 5–6 year olds displaying the worst thresholds with 2 AM cycles, but similar thresholds with 8 cycles compared to the 7–8 and 10–11 year olds, and, (ii) adults showing the best thresholds with 8 AM cycles but similar thresholds with 2 cycles compared to the 7–8 and 10–11 year olds. Computational modelling indicated that higher levels of internal noise combined with poorer short-term memory capacities in children accounted for the developmental trends. Improvement in processing efficiency may therefore account for the development of AM detection in childhood

Snake orbits and related magnetic edge states

We study the electron motion near magnetic field steps at which the strength and/or sign of the magnetic field changes. The energy spectrum for such systems is found and the electron states (bound and scattered) are compared with their corresponding classical paths. Several classical properties as the velocity parallel to the edge, the oscillation frequency perpendicular to the edge and the extent of the states are compared with their quantum mechanical counterpart. A class of magnetic edge states is found which do not have a classical counterpart.Comment: 8 pages, 10 figure

Magnetic Moment Softening and Domain Wall Resistance in Ni Nanowires

Magnetic moments in atomic scale domain walls formed in nanoconstrictions and nanowires are softened which affects dramatically the domain wall resistance. We perform ab initio calculations of the electronic structure and conductance of atomic-size Ni nanowires with domain walls only a few atomic lattice constants wide. We show that the hybridization between noncollinear spin states leads to a reduction of the magnetic moments in the domain wall. This magnetic moment softening strongly enhances the domain wall resistance due to scattering produced by the local perturbation of the electronic potential.Comment: 4 pages, 5 figure