Artificial pancreas (AP) is an important treatment for patients with Type 1 diabetes (T1D). The control algorithm adopted in an AP system determines its reliability and accuracy. The generalized predictive control (GPC) is a representative adaptive control algorithm and has been widely applied to AP systems. However, we found that the traditional GPC controller does not work well for adolescents with T1D because of their high-fluctuating blood glucose and high insulin resistance. Here, we propose an improved GPC algorithm with an adaptive reference glucose trajectory and an adaptive softening factor. The slopes of the reference trajectory and the value of softening factor are calculated real-time on the basis of the blood glucose concentration (BGC) variations. In silico testing was done using the US Food and Drug Administration (FDA) approved virtual patient software T1D mellitus. The BGC trace and density of 20 patient-subjects (10 adults and 10 adolescents) were recorded. Results showed that the average BGC percentage within the target regions (70-180 mg/dL) of the tests with adaptive reference glucose trajectory and softening factor for adolescents (0.93 ± 0.07) was significantly higher than that of the traditional GPC algorithm tests (0.88 ± 0.11), suggesting that the control quality of the blood glucose of adolescents is significantly improved with our GPC algorithm. Therefore, our improved GPC controller is effective and should have a good applicability in AP systems.

The blockade of immune checkpoints, such as programmed death receptor 1 (PD-1) and programmed death ligand 1 protein (PD-L1), is a promising therapeutic approach in cancer immunotherapy. Nivolumab, a humanized IgG4 antibody targeting PD-1, was approved by the US Food and Drug Administration for several cancers in 2014. Crystal structures of the nivolumab/PD-1 complex show that the epitope of PD-1 locates at the IgV domain (including the FG and BC loops) and the N-terminal loop. Although the N-terminal loop of PD-1 has been shown to play a dominant role in the complex interface of the static structure, its role in the dynamic binding process has not been illustrated clearly. Here, eight molecular systems were established for nivolumab/PD-1 complex, and long-time molecular dynamics simulations were performed for each. Results showed that the N-terminal loop of PD-1 prefers to bind with nivolumab to stabilize the interface between IgV and nivolumab. Furthermore, the binding of the N-terminal loop with nivolumab induces the rebinding between the IgV domain and nivolumab. Thus, we proposed a two-step binding model for the nivolumab/PD-1 binding, where the interface switches to a high-affinity state with the help of the N-terminal loop. This finding suggests that the N-terminal loop of PD-1 might be a potential target for anti-PD-1 antibody design, which could serve as an important gatekeeper for the anti-PD-1 antibody binding.

Wearing hearing aids can help hearing impaired patients enter the sound world, so as to improve their quality of life. Hearing aid fitting is highly professional and requires long-term after-sales service. This paper takes 300 impaired patients and 50 hearing aid fitters of Siemens hearing aid fitting Engineer as the research object to analyze the main influencing factors of hearing impaired patients' purchase of hearing aids and the key factors to improve long-term satisfaction. Hearing aid effect, wearing comfort and service quality significantly affect the long-term satisfaction of hearing-impaired patients. Brand, price, refined customer relationship maintenance and technical personification have a positive impact on customer repeat purchase and recommendation.

This paper reports a micro optical power meter which is able to perform effective and precise measurement on the optical power at the focus of different microscopic systems. The power meter can be easily placed on the stages of different microscopes and even partly immersed into solution to directly measure the optical power transmitted from the microscope objective and focused on the sample suspended in solution. The testing experiments demonstrated that the power meter has the characteristics of high precision, excellent linearity, high sensitivity, good stability, and high responding speed. It can accurately measure power levels from 0.1 to 50 mW in visible wavelength in various conditions and environments, which may encounter in practical applications. The optical power measurements using the power meter performed in some biological cell culturing solutions and in air for the same laser light reveal the first time that the powers measured in solutions were about 5%-8% greater than that measured in air at the same position. This not only suggests the necessity of performing direct measurement in situ in solution to obtain the real optical power projected on the suspended samples, but also indicates that such a micro optical power meter can meet almost all the requirements of optical power measurement in different fields from biomedicine to material sciences.

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