Combined 13C-assisted metabolomics and metabolic flux analysis reveals the impacts of glutamate on the central metabolism of high β-galactosidase-producing Pichia pastoris

BACKGROUND: Pichia pastoris is a popular recombinant protein expression system for its accessibility of efficient gene manipulation and high protein production. Sufficient supply of precursors, energy, and redox cofactors is crucial for high recombinant protein production. In our present work, we found that the addition of glutamate improved the recombinant β-galactosidase (β-gal) production by P. pastoris G1HL. METHODS: To elucidate the impacts of glutamate on the central metabolism in detail, a combined (13)C-assisted metabolomics and (13)C metabolic flux analysis was conducted based on LC–MS/MS and GC–MS data. RESULTS: The pool sizes of intracellular amino acids were obviously higher on glucose/glutamate (Glc/Glu). The fluxes in EMP entry reaction and in downstream TCA cycle were 50 and 67% higher on Glc/Glu than on Glc, respectively. While the fluxes in upstream TCA cycle kept almost unaltered, the fluxes in PPP oxidative branch decreased. CONCLUSION: The addition of glutamate leads to a remarkable change on the central metabolism of high β-galactosidase-producing P. pastoris G1HL. To meet the increased demands of redox cofactors and energy for higher β-galactosidase production on Glc/Glu, P. pastoris G1HL redistributes the fluxes in central metabolism through the inhibitions and/or activation of the enzymes in key nodes together with the energy and redox status. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s40643-016-0124-6) contains supplementary material, which is available to authorized users

Accelerated Policy Gradient: On the Nesterov Momentum for Reinforcement Learning

Policy gradient methods have recently been shown to enjoy global convergence at a $\Theta(1/t)$ rate in the non-regularized tabular softmax setting. Accordingly, one important research question is whether this convergence rate can be further improved, with only first-order updates. In this paper, we answer the above question from the perspective of momentum by adapting the celebrated Nesterov's accelerated gradient (NAG) method to reinforcement learning (RL), termed \textit{Accelerated Policy Gradient} (APG). To demonstrate the potential of APG in achieving faster global convergence, we formally show that with the true gradient, APG with softmax policy parametrization converges to an optimal policy at a $\tilde{O}(1/t^2)$ rate. To the best of our knowledge, this is the first characterization of the global convergence rate of NAG in the context of RL. Notably, our analysis relies on one interesting finding: Regardless of the initialization, APG could end up reaching a locally nearly-concave regime, where APG could benefit significantly from the momentum, within finite iterations. By means of numerical validation, we confirm that APG exhibits $\tilde{O}(1/t^2)$ rate as well as show that APG could significantly improve the convergence behavior over the standard policy gradient.Comment: 51 pages, 8 figure

Research status of channel estimation and signal detection techniques for orthogonal time frequency space modulation

Orthogonal time frequency space (OTFS) modulation is a multiplexing technique designed in the two-dimensional (2D) delay-Doppler domain suited for high Doppler fading channels. OTFS converts a doubly-selective channel into an almost non-fading channel in the delay-Doppler domain through a series of 2D transformations. OTFS has the potential of capturing time-frequency full diversity. In order to obtain the time-frequency full diversity gain, a receiver with advanced channel estimation and signal detection algorithm is needed. The basic principle and system model of OTFS was firstly introduced, then the existing channel estimation and signal detection algorithms were reviewed, finally the future challenges and solutions for channel estimation and signal detection were discussed

The CDEX-1 1 kg Point-Contact Germanium Detector for Low Mass Dark Matter Searches

The CDEX Collaboration has been established for direct detection of light dark matter particles, using ultra-low energy threshold p-type point-contact germanium detectors, in China JinPing underground Laboratory (CJPL). The first 1 kg point-contact germanium detector with a sub-keV energy threshold has been tested in a passive shielding system located in CJPL. The outputs from both the point-contact p+ electrode and the outside n+ electrode make it possible to scan the lower energy range of less than 1 keV and at the same time to detect the higher energy range up to 3 MeV. The outputs from both p+ and n+ electrode may also provide a more powerful method for signal discrimination for dark matter experiment. Some key parameters, including energy resolution, dead time, decay times of internal X-rays, and system stability, have been tested and measured. The results show that the 1 kg point-contact germanium detector, together with its shielding system and electronics, can run smoothly with good performances. This detector system will be deployed for dark matter search experiments.Comment: 6 pages, 8 figure

Capacity analysis for MISO-UWOC systems over GGD weak turbulence with zero boresight pointing error

Generalized Gamma distribution (GGD) was chosen to describe the weak oceanic turbulence, and a new hybrid fading channel model that integrated the GGD weak turbulence, the zero boresight pointing error, and the implicit path loss plus multipath propagation characterized by the fading free impulse response (FFIR) was proposed.Subsequently, mathematical expressions for the ergodic capacity and outage capacity of the multiple-input single-output underwater wireless optical communication (MISO-UWOC) systems were derived through the Meijer-G function under a selective transmission (ST) diversity scheme especially while inter-symbol interference (ISI) effects were considered or not.Finally, the correctness of the theoretical formulas derived above was verified by some numerical results.The simulation results show that with the introduction of the ST diversity, the ergodic capacity of the MISO-UWOC systems, taking the transmission ports N=2 as an example, is at least 1.3 times better than that of the conventional point-to-point (P2P) transmission under the same channel condition and system parameters, while the maximum outage capacity decreases is also more than 60% compared with the conventional P2P one.However, the introduction of the ISI will severely reduce this performance improvement

Single-particle measurements of electrochemical kinetics in NMC and NCA cathodes for Li-ion batteries

The electrochemical kinetics of battery electrodes at the single-particle scale are measured as a function of state-of-charge, and interpreted with the aid of concurrent transmission X-ray microscopy (TXM) of the evolving particle microstructure. An electrochemical cell operating with near-picoampere current resolution is used to characterize single secondary particles of two widely-used cathode compounds, NMC333 and NCA. Interfacial charge transfer kinetics are found to vary by two orders of magnitude with state-of-charge (SOC) in both materials, but the origin of the SOC dependence differs greatly. NCA behavior is dominated by electrochemically-induced microfracture, although thin binder coatings significantly ameliorate mechanical degradation, while NMC333 demonstrates strongly increasing interfacial reaction rates with SOC for chemical reasons. Micro-PITT is used to separate interfacial and bulk transport rates, and show that for commercially relevant particle sizes, interfacial transport is rate-limiting at low SOC, while mixed-control dominates at higher SOC. These results provide mechanistic insight into the mesoscale kinetics of ion intercalation compounds, which can guide the development of high performance rechargeable batteries

Changes in fertility intention and symptom burden in reproductive-age women with breast cancer

With this study, we aimed (1) to examine the changes in fertility intention and symptom burden before, during, and after treatment and (2) to explore predictors of fertility intention in reproductive-age women with breast cancer