A new application-specific integrated circuit (ASIC), the high-speed chargeto-time converter (QTC) IWATSU CLC101, provides three channels, each consisting of preamplifier, discriminator, low-pass filter, and charge integration circuitry, optimized for the waveform of a photomultiplier tube (PMT). This ASIC detects PMT signals using individual built-in discriminators and drives output timing signals whose width represents the integrated charge of the PMT signal. Combined with external input circuits composed of passive elements, the QTC provides full analog signal processing for the detector's PMTs, ready for further processing by time-to-digital converters (TDCs). High-rate (>1 MHz) signal processing is achieved by short-charge-conversiontime and baseline-restoration circuits. Wide-range charge measurements are enabled by offering three gain ranges while maintaining a short cycle time. QTC chip test results show good analog performance, with efficient detection for a single photoelectron signal, 4 orders of magnitude dynamic range (0.3 mV ∼ 3 V; 0.2 ∼ 2500 pC), 1% charge linearity, 0.2 pC charge resolution, and 0.1 ns timing resolution. Test results on ambient temperature dependence, channel isolation, and rate dependence also meet specifications.
BackgroundMicroglia, one of the glial cells, play important roles in various brain pathologies including psychiatric disorders. In addition, microglia have recently been proved to monitor synaptic reactions via direct-touching even in normal brain. Human microglia may modulate various social/mental functions, while microglial social/mental roles remain unresolved especially in healthy humans. There is no known drug with the specific effect of modulating microglia. Therefore, using minocycline, a tetracycline antibiotic and the most famous microglial inhibitor, is one of the best alternative approaches to clarify microglial functions on human social/mental activities.Methodology/Principal FindingsWe conducted a double-blind randomized trial of trust game, a monetary decision-making experiment, with ninety-nine human adult males who decided how much to trust an anonymous partner after a four-day administration of minocycline. Our previous pilot trial indicated a positive effect of minocycline, while the underlying mechanisms were not clarified. Therefore, in this trial with larger samples, we additionally measured the effects of anxiety and personality. The monetary score in trust game was significantly lower in the minocycline group. Interestingly, participants’ ways of decision-making were significantly shifted; cooperativeness, one component of personality, proved to be the main modulating factor of decision-making in the placebo group, on the other hand, the minocycline group was mainly modulated by state anxiety and trustworthiness.Conclusions/SignificanceOur results suggest that minocycline led to more situation-oriented decision-making, possibly by suppressing the effects of personality traits, and furthermore that personality and social behaviors might be modulated by microglia. Early-life events may activate human microglia, establish a certain neuro-synaptic connection, and this formation may determine each human’s personality and personality- oriented social behaviors in later life. To explore these mechanisms, further translational research is needed.Trial RegistrationUMIN clinical trial center UMIN000004803
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