RESUMEN
We report the observation of a steepening in the cosmic ray energy spectrum of heavy primary particles at about 8×10(16) eV. This structure is also seen in the all-particle energy spectrum, but is less significant. Whereas the "knee" of the cosmic ray spectrum at 3-5×10(15) eV was assigned to light primary masses by the KASCADE experiment, the new structure found by the KASCADE-Grande experiment is caused by heavy primaries. The result is obtained by independent measurements of the charged particle and muon components of the secondary particles of extensive air showers in the primary energy range of 10(16) to 10(18) eV. The data are analyzed on a single-event basis taking into account also the correlation of the two observables.
RESUMEN
BACKGROUND: The insulin-independent inhibition of lipolysis by palmitate, the anti-diabetic sulphonylurea glimepiride and H2O2 in rat adipocytes involves stimulation of the glycosylphosphatidylinositol (GPI)-specific phospholipase-C (GPI-PLC) and subsequent translocation of the GPI-anchored membrane ectoproteins (GPI-proteins), Gce1 and cluster of differentiation antigen (CD73), from specialized plasma membrane microdomains (DIGs) to cytosolic lipid droplets (LDs). This results in cAMP degradation at the LD surface and failure to activate hormone-sensitive lipase. Reactive oxygen species (ROS) may trigger this sequence of events in response to palmitate and glimepiride. EXPERIMENTAL APPROACH: The effects of various inhibitors of ROS production on the release of H2O2, GPI anchor cleavage and translocation of the photoaffinity-labelled or metabolically labelled Gce1 and CD73 from DIGs to LD and inhibition of lipolysis by different fatty acids and sulphonylureas were studied with primary rat adipocytes. KEY RESULTS: Glimepiride and palmitate induced the production of H2O2 via the plasma membrane NADPH oxidase and mitochondrial complexes I and III, respectively. Inhibition of ROS production was accompanied by the loss of (i) GPI-PLC activation, (ii) Gce1 and CD73 translocation and (iii) lipolysis inhibition in response to palmitate and glimepiride. Non-metabolizable fatty acids and the sulphonylurea drug tolbutamide were inactive. NADPH oxidase and GPI-PLC activities colocalized at DIGs were stimulated by glimepiride but not tolbutamide. CONCLUSIONS AND IMPLICATIONS: The data suggest that ROS mediate GPI-PLC activation at DIGs and subsequent GPI-protein translocation from DIGs to LD in adipocytes which leads to inhibition of lipolysis by palmitate and glimepiride. This insulin-independent anti-lipolytic mechanism may be engaged by future anti-diabetic drugs.
Asunto(s)
Glicosilfosfatidilinositol Diacilglicerol-Liasa/metabolismo , Glicosilfosfatidilinositoles/metabolismo , Peróxido de Hidrógeno/metabolismo , Especies Reactivas de Oxígeno/metabolismo , 5'-Nucleotidasa/metabolismo , Adipocitos , Animales , AMP Cíclico/metabolismo , Ácidos Grasos/farmacología , Lipólisis/efectos de los fármacos , Microdominios de Membrana/metabolismo , NADPH Oxidasas/metabolismo , Transporte de Proteínas , Ratas , Especies Reactivas de Oxígeno/antagonistas & inhibidores , Compuestos de Sulfonilurea/farmacologíaRESUMEN
A case study of the first deaf-blind patient implanted with a Nucleus 22 channel cochlear prosthesis is presented. The patient's preimplant evaluation data, using a powerful hearing aid and vibro-tactile device, are compared with results obtained 8 months postimplant. Preimplant testing indicated no consistent response to sound. Postimplant testing showed ability to comprehend some open set speech with hearing alone through the cochlear implant including ability to utilize the telephone without a code system. The postimplant data suggest potential benefit for other postlingually deaf-blind individuals from multichannel cochlear stimulation.
Asunto(s)
Ceguera/complicaciones , Implantes Cocleares , Sordera/rehabilitación , Percepción del Habla , Ceguera/fisiopatología , Sordera/complicaciones , Sordera/fisiopatología , Femenino , Humanos , Persona de Mediana Edad , Pruebas de Discriminación del HablaRESUMEN
Increasing the degree of effort required for the successful performance of one behavior has been found to heighten the subsequent performance of other behaviors. The present research tested whether discriminative stimuli for effort control the quantity and quality of transfer performance. Two experimenters administered alternately a perceptual task which required college students to identify subtle differences between cartoon drawings. The high-effort experimenter required five identifications per pair of drawings; the low-effort experimenter, one identification. The later assignment of an essay by the high-effort experimenter, as compared to the low-effort experimenter, resulted in a greater essay length and quality. These findings suggest that cues which signal the degree of effort required for reinforcement exert discriminative control over generalized effort.