In addition to dopaminergic hyperactivity, hypofunction of the N-methyl-D-aspartate receptor (NMDAR) has an important role in the pathophysiology of schizophrenia. Enhancing NMDAR-mediated neurotransmission is considered a novel treatment approach. To date, several trials on adjuvant NMDA-enhancing agents have revealed beneficial, but limited, efficacy for positive and negative symptoms and cognition. Another method to enhance NMDA function is to raise the levels of D-amino acids by blocking their metabolism. Sodium benzoate is a D-amino acid oxidase inhibitor.OBJECTIVE To examine the clinical and cognitive efficacy and safety of add-on treatment of sodium benzoate for schizophrenia.
DESIGN, SETTING, AND PARTICIPANTSA randomized, double-blind, placebo-controlled trial in 2 major medical centers in Taiwan composed of 52 patients with chronic schizophrenia who had been stabilized with antipsychotic medications for 3 months or longer.INTERVENTIONS Six weeks of add-on treatment of 1 g/d of sodium benzoate or placebo.
MAIN OUTCOMES AND MEASURESThe primary outcome measure was the Positive and Negative Syndrome Scale (PANSS) total score. Clinical efficacy and adverse effects were assessed biweekly. Cognitive functions were measured before and after the add-on treatment.RESULTS Benzoate produced a 21% improvement in PANSS total score and large effect sizes (range, 1.16-1.69) in the PANSS total and subscales, Scales for the Assessment of Negative Symptoms-20 items, Global Assessment of Function, Quality of Life Scale and Clinical Global Impression and improvement in the neurocognition subtests as recommended by the National Institute of Mental Health's Measurement and Treatment Research to Improve Cognition in Schizophrenia initiative, including the domains of processing speed and visual learning. Benzoate was well tolerated without significant adverse effects.
CONCLUSIONS AND RELEVANCEBenzoate adjunctive therapy significantly improved a variety of symptom domains and neurocognition in patients with chronic schizophrenia. The preliminary results show promise for D-amino acid oxidase inhibition as a novel approach for new drug development for schizophrenia. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT 00960219
SignificanceWe constructed an Escherichia coli strain that does not use glycolysis for sugar catabolism. Instead, it uses the synthetic nonoxidative glycolysis cycle to directly synthesize stoichiometric amounts of the two-carbon building block (acetyl-CoA), which is then converted to three-carbon metabolites to support growth. The resulting strain grows aerobically in glucose minimal medium and can achieve near-complete carbon conservation in the production of acetyl-CoA–derived products during anaerobic fermentation. This strain improves the theoretical carbon yield from 66.7% to 100% in acetyl-CoA–derived product formation.
In this research, five sizes (100 × 100, 75 × 75, 50 × 50, 25 × 25, 10 × 10 µm2) of InGaN red micro-light emitting diode (LED) dies are produced using laser-based direct writing and maskless technology. It is observed that with increasing injection current, the smaller the size of the micro-LED, the more obvious the blue shift of the emission wavelength. When the injection current is increased from 0.1 to 1 mA, the emission wavelength of the 10 × 10 μm2 micro-LED is shifted from 617.15 to 576.87 nm. The obvious blue shift is attributed to the stress release and high current density injection. Moreover, the output power density is very similar for smaller chip micro-LEDs at the same injection current density. This behavior is different from AlGaInP micro-LEDs. The sidewall defect is more easily repaired by passivation, which is similar to the behavior of blue micro-LEDs. The results indicate that the red InGaN epilayer structure provides an opportunity to realize the full color LEDs fabricated by GaN-based LEDs.
In the past decade, the development of synthetic gene networks has attracted much attention from many researchers. In particular, the genetic oscillator known as the repressilator has become a paradigm for how to design a gene network with a desired dynamic behaviour. Even though the repressilator can show oscillatory properties in its protein concentrations, their amplitudes, frequencies and phases are perturbed by the kinetic parametric fluctuations (intrinsic molecular perturbations) and external disturbances (extrinsic molecular noises) of the environment. Therefore, how to design a robust genetic oscillator with desired amplitude, frequency and phase under stochastic intrinsic and extrinsic molecular noises is an important topic for synthetic biology.In this study, based on periodic reference signals with arbitrary amplitudes, frequencies and phases, a robust synthetic gene oscillator is designed by tuning the kinetic parameters of repressilator via a genetic algorithm (GA) so that the protein concentrations can track the desired periodic reference signals under intrinsic and extrinsic molecular noises. GA is a stochastic optimization algorithm which was inspired by the mechanisms of natural selection and evolution genetics. By the proposed GA-based design algorithm, the repressilator can track the desired amplitude, frequency and phase of oscillation under intrinsic and extrinsic noises through the optimization of fitness function.The proposed GA-based design algorithm can mimic the natural selection in evolutionary process to select adequate kinetic parameters for robust genetic oscillators. The design method can be easily extended to any synthetic gene network design with prescribed behaviours.
The impact of intrinsic amorphous silicon bilayers in amorphous silicon/crystalline silicon (a-Si:H/c-Si) heterojunction solar cells is investigated. The microstructure factor R* of the interfacial a-Si:H layer, which is related to the Si-H bond microstructure and determined by infrared absorption spectroscopy, is controlled in a wide range by varying the growth pressure and the power density in plasma-enhanced chemical vapor deposition process. Surface passivation at the a-Si:H/c-Si interface is significantly improved by using an intrinsic a-Si:H bilayer, i.e., a stack of an interfacial layer with a large R* and an additional dense layer, particularly after the deposition of an overlying p-type a-Si:H layer. Consequently, the conversion efficiency of a-Si:H/c-Si heterojunction solar cells is markedly increased. However, it is also revealed that such an interfacial layer causes some negative effects including the increase in the series resistance and the current loss at the front side, depending on the growth condition. This result indicates that the interfacial layer has a significant impact on both the majority and the minority carrier transport. Thus, R* of the interfacial layer is an important parameter for obtaining good surface passivation at the a-Si/c-Si interface, but not the sole parameter determining the conversion efficiency of a-Si:H/c-Si heterojunction solar cells.
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