RESUMEN
An all solid-state, megawatt-class high power microwave system featuring a silicon carbide (SiC) photoconductive semiconductor switch (PCSS) and a ferrimagnetic-based, coaxial nonlinear transmission line (NLTL) is presented. A 1.62 cm(2), 50 kV 4H-SiC PCSS is hard-switched to produce electrical pulses with 7 ns full width-half max (FWHM) pulse widths at 2 ns risetimes in single shot and burst-mode operation. The PCSS resistance drops to sub-ohm when illuminated with approximately 3 mJ of laser energy at 355 nm (tripled Nd:YAG) in a single pulse. Utilizing a fiber optic based optical delivery system, a laser pulse train of four 7 ns (FWHM) signals was generated at 65 MHz repetition frequency. The resulting electrical pulse train from the PCSS closely follows the optical input and is utilized to feed the NLTL generating microwave pulses with a base microwave-frequency of about 2.1 GHz at 65 MHz pulse repetition frequency (prf). Under typical experimental conditions, the NLTL produces sharpened output risetimes of 120 ps and microwave oscillations at 2-4 GHz that are generated due to damped gyromagnetic precession of the ferrimagnetic material's axially pre-biased magnetic moments. The complete system is discussed in detail with its output matched into 50 Ω, and results covering MHz-prf in burst-mode operation as well as frequency agility in single shot operation are discussed.
RESUMEN
This paper discusses a compact high voltage curve tracer for high voltage semiconductor device characterization. The system sources up to 3 mA at up to 45 kV in dc conditions. It measures from 328 V to 60 kV with 15 V resolution and from 9.4 pA to 4 mA with 100 fA minimum resolution. Control software for the system is written in Microsoft Visual C# and features real-time measurement control and IV plotting, arc-protection and detection, an electrically isolated universal serial bus interface, and easy data exporting capabilities. The system has survived numerous catastrophic high voltage device-under-test arcing failures with no loss of measurement capability or system damage. Overall sweep times are typically under 2 min, and the curve tracer system was used to characterize the blocking performance of high voltage ceramic capacitors, high voltage silicon carbide photoconductive semiconductor switches, and high voltage coaxial cable.
RESUMEN
The molecular mechanisms controlling synaptogenesis in the central nervous system (CNS) are poorly understood. Previous reports showed that a glia-derived factor strongly promotes synapse development in cultures of purified CNS neurons. Here, we identify this factor as cholesterol complexed to apolipoprotein E-containing lipoproteins. CNS neurons produce enough cholesterol to survive and grow, but the formation of numerous mature synapses demands additional amounts that must be provided by glia. Thus, the availability of cholesterol appears to limit synapse development. This may explain the delayed onset of CNS synaptogenesis after glia differentiation and neurobehavioral manifestations of defects in cholesterol or lipoprotein homeostasis.
Asunto(s)
Colesterol/metabolismo , Lovastatina/análogos & derivados , Neuroglía/metabolismo , Células Ganglionares de la Retina/fisiología , Sinapsis/fisiología , Animales , Anticolesterolemiantes/farmacología , Apolipoproteínas E/metabolismo , Células Cultivadas , Colesterol/farmacología , Medios de Cultivo Condicionados , Potenciales Postsinápticos Excitadores , Lovastatina/farmacología , Técnicas de Placa-Clamp , Fosfatidilcolinas/farmacología , Ratas , Ratas Sprague-Dawley , Células Ganglionares de la Retina/metabolismo , Esfingomielinas/farmacología , Sinapsis/efectos de los fármacos , Transmisión SinápticaRESUMEN
1. To study the effects of glial cells on synapse formation, we established microcultures of purified rat retinal ganglion cells (RGCs) and monitored synapse (autapse) development in single neurones using electrophysiological recordings, FM1-43 labelling and immunocytochemistry. 2. Solitary neurones grew ramifying neurites, but formed only very few and inefficient excitatory autapses, when cultured for up to 2 weeks in defined medium and in the absence of glial cells. 3. Treatment of glia-free microcultures of RGCs with glia-conditioned medium (GCM) increased the number of autapses per neurone by up to 10-fold. This was indicated by a similar increase in the frequency of spontaneous events and the number of FM1-43-labelled functional release sites and of puncta, where pre- and postsynaptic markers colocalized. 4. In addition, GCM treatment enhanced the efficacy of presynaptic transmitter release as indicated by lower failure rates of stimulation-induced excitatory autaptic currents, a 200-fold increase in the frequency of asynchronous release and an accelerated stimulation-induced FM1-43 destaining. Furthermore, GCM induced an increase in the quantal size. 5. GCM affected autaptic activity not immediately, but with a delay of 24 h, and the effects on stimulation-induced autaptic currents occurred before changes in the frequency of spontaneous events indicating an early strengthening of existing autapses followed by a later increase in autapse number. 6. The observed effects were mediated by proteinase K-sensitive factors in GCM and occurred independently of electrical activity. 7. These results suggest that soluble glia-derived signals induce synapse formation and maturation in neurones of the central nervous system (CNS).
Asunto(s)
Neuroglía/fisiología , Neuronas/fisiología , Transducción de Señal/fisiología , Sinapsis/fisiología , Animales , Comunicación Celular , Células Cultivadas , Medios de Cultivo Condicionados/farmacología , Conductividad Eléctrica , Electrofisiología , Endopeptidasa K/farmacología , Colorantes Fluorescentes , Inmunohistoquímica , Neuroglía/metabolismo , Compuestos de Piridinio , Compuestos de Amonio Cuaternario , Ratas , Ratas Sprague-Dawley , Células Ganglionares de la Retina/fisiología , Transmisión Sináptica/fisiología , Factores de TiempoRESUMEN
Death receptors can trigger cell demise dependent or independent of caspases. In WEHI-S fibrosarcoma cells, tumor necrosis factor (TNF) induced an increase in cytosolic cathepsin B activity followed by death with apoptotic features. Surprisingly, this process was enhanced by low, but effectively inhibiting, concentrations of pan-caspase inhibitors. Contrary to caspase inhibitors, a panel of pharmacological cathepsin B inhibitors, the endogenous cathepsin inhibitor cystatin A as well as antisense-mediated depletion of cathepsin B rescued WEHI-S cells from apoptosis triggered by TNF or TNF-related apoptosis-inducing ligand. Thus, cathepsin B can take over the role of the dominant execution protease in death receptor-induced apoptosis. The conservation of this alternative execution pathway was further examined in other tumor cell lines. Here, cathepsin B acted as an essential downstream mediator of TNF-triggered and caspase-initiated apoptosis cascade, whereas apoptosis of primary cells was only minimally dependent on cathepsin B. These data imply that cathepsin B, which is commonly overexpressed in human primary tumors, may have two opposing roles in malignancy, reducing it by its proapoptotic features and enhancing it by its known facilitation of invasion.