5-HTR2A is involved in melanogenesis. These findings highlight the role of 5-HT and suggest new ways of controlling melanogenesis.

Since the first H-mode discharges in 2010, the duration of the H-mode state has been extended and a significantly wider operational window of plasma parameters has been attained. Using a second neutral beam (NB) source and improved tuning of equilibrium configuration with real-time plasma control, a stored energy of W tot ∼ 450 kJ has been achieved with a corresponding energy confinement time of τ E ∼ 163 ms. Recent discharges, produced in the fall of 2012, have reached plasma β N up to 2.9 and surpassed the n = 1 ideal no-wall stability limit computed for H-mode pressure profiles, which is one of the key threshold parameters defining advanced tokamak operation. Typical H-mode discharges were operated with a plasma current of 600 kA at a toroidal magnetic field B T = 2 T. L-H transitions were obtained with 0.8-3.0 MW of NB injection power in both single-and double-null configurations, with H-mode durations up to ∼15 s at 600 kA of plasma current. The measured power threshold as a function of lineaveraged density showed a roll-over with a minimum value of ∼0.8 MW at ne ∼ 2×10 19 m −3 . Several edge-localized mode (ELM) control techniques during H-mode were examined with successful results including resonant magnetic perturbation, supersonic molecular beam injection (SMBI), vertical jogging and electron cyclotron current drive injection into the pedestal region. We observed various ELM responses, i.e. suppression or mitigation, depending on the relative phase of in-vessel control coil currents. In particular, with the 90 • phase of the n = 1 RMP as the most resonant configuration, a complete suppression of type-I ELMs was demonstrated. In addition, fast vertical jogging of the plasma column was also observed to be effective in ELM pace-making. SMBI-mitigated ELMs, a state of mitigated ELMs, were sustained for a few tens of ELM periods. A simple cellular automata ('sand-pile') model predicted that shallow deposition near the pedestal foot induced small-sized high-frequency ELMs, leading to the mitigation of large ELMs. In addition to the ELM control experiments, various physics topics were explored focusing on ITER-relevant physics issues such as the alteration of toroidal rotation caused by both electron cyclotron resonance heating (ECRH) and externally applied 3D fields, and the observed rotation drop by ECRH in NB-heated plasmas was investigated in terms of either a reversal of the turbulence-driven residual stress due to the transition of ion temperature gradient to trapped electron mode turbulence or neoclassical toroidal viscosity (NTV) torque by the internal kink mode. The suppression of runaway electrons using massive gas injection of deuterium showed that runaway electrons were avoided only below 3 T in KSTAR. Operation in 2013 is expected to routinely exceed the n = 1 ideal MHD no-wall stability boundary in the long-pulse H-mode ( 10 s) by applying real-time shaping control, enabling n = 1 resistive wall mode active control studies. In addition, intensive works for ELM mitigation, ELM dynamics, toroidal ro...

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Protein-calorie malnutrition (PCM) occurs frequently in advanced cancer patients and has a profound impact on the toxicity of many drugs. Thus, the pharmacokinetics of etoposide were evaluated in control, control with cysteine (CC), PCM, and PCM with cysteine (PCMC) rats. Etoposide was administered intravenously (2 mg/kg) or orally (10 mg/kg). Changes in hepatic and intestinal cytochrome P450s (CYPs) and effects of cysteine on intestinal P-glycoprotein (P-gp)-mediated efflux were also measured. In PCM rats, the CL(NR) (AUC(0-∞)) of intravenous etoposide was significantly slower (greater) than that in controls, because of the significant decrease in the hepatic CYP3A subfamily and P-gp. In PCMC rats, the slowed CL(NR) of etoposide in PCM rats was restored to the control level by cysteine treatment. PCMC rats showed a significantly greater AUC(0-6 h) of oral etoposide than PCM rats, primarily because of the increased gastrointestinal absorption of etoposide as a result of the inhibition of intestinal P-gp by cysteine. The gastrointestinal absorption of an oral anticancer drug, which is a substrate of P-gp, may be improved by co-administration of cysteine in advanced cancer patients if the present rat data can be extrapolated to patients.

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