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In this paper, a Super-twisting sliding-mode control method based on a nonlinear interference observer is proposed for the external perturbation of MEMS micromirrors during beam scanning. Developing a physical model of electrostatic MEMS micromirror, the Super-twisting sliding-mode control algorithm based on nonlinear interference observer is applied to the electrostatically driven MEMS scanning micromirror with side electrodes, with the demonstration on stability of the control system by Lyapunov theory. The method effectively improves the anti-disturbance performance of the system. The simulation results show that the Super-twisting sliding mode control method based on nonlinear disturbance observer can effectively enhance the disturbance inhibition of the system.

Laser beam scanning technology has been widely used in various fields such as LIDAR, photoelectric detection and space optical communication, etc. Mechanical scanning has problems such as inflexibility and low scanning rate. This paper introduces the basic principles of acoustic-optical scanning, electro-optical scanning, optical phased array and MEMS scanning, and analyses the advantages and disadvantages of several scanning methods and the main application scenarios, and finds that the current optical scanning technology is developing towards large scanning angle, high accuracy, fast response and miniaturization, among which the liquid crystal optical phased array and MEMS scanning technology are relatively mature. The scanning angle of the LCD optical phased array can reach ±10°, and the scanning angle of the MEMS can reach 6.6°*4.4°, which has a broad development prospect.

Ultra-fine 2,2’,4,4’,6,6’- Hexanitrostilbene (HNS-IV) was obtained by HNS-II by vibration cavity comminute. This method uses only alcohol and deionized water, which can be viewed as a green technology. The morphology, particle size, specific surface area, thermal decomposition property and the threshold energy for slapper detonator were compared between HNS-IV and HNS-II in this paper. Results show that after HNS pulverizing, the particle size decreased from 27.18μm to 1.44μm, the specific surface area increased from 0.73m 2• g −1 to 9.10m 2• g −1 . DSC analysis shows that the decomposition peak temperature T d decreases and the melting temperature T m increases after pulverizing. It is speculated that in the explosive reaction with very high heating rate, the enthalpy of decomposition will be increased by pulverizing, which will be more conducive to detonation growth and explosive reaction. According to the calculation of thermal decomposition kinetics, the decomposition and activation energy Ea of HNS decreases after pulverizing, and the thermal decomposition reaction rate of HNS-IV increases when the temperature is less than 409.6°C. The initiation threshold test of the impact plate shows that the 50% initiation threshold energy of HNS- II is 1.242J, and the 50% initiation threshold energy of HNS-IV is 0.558J, and the initiation threshold for slapper detonatorer is significantly reduced by 55%. This means that the ultra-fine HNS-IV is very suitable as the main ingredient in the booster in the EFI initiation.

The Ca2＋/calmodulin-dependent protein phosphatase calcineurin （CN）, a heterodimer composed of a catalytic subunit A and an essential regulatory subunit B, plays critical functions in various cellular processes such as cardiac hypertrophy and T cell activation. It is the target of the most widely used immunosuppressants for transplantation, tacrolimus （FKS06） and cyclosporin A. However, the structure of a large part of the CNA regulatory region remains to be determined, and there has been considerable debate concerning the regulation of CN activity. Here, we report the crystal structure of full-length CN （β isoform）, which revealed a novel autoinhibitory segment （AIS） in addition to the well-known autoinhibitory domain （AID）. The AIS nestles in a hydrophobic intersubunit groove, which over- laps the recognition site for substrates and immunosuppressant-immunophilin complexes. Indeed, disruption of this AIS interaction results in partial stimulation of CN activity. More importantly, our biochemical studies demonstrate that calmodulin does not remove AID from the active site, but only regulates the orientation of AID with respect to the catalytic core, causing incomplete activation of CN. Our findings challenge the current model for CN activation, and provide a better understanding of molecular mechanisms of CN activity regulation.

The self-similar multiplicative theory（SSM theory）, aims to interpret the scaling behavior of the temperature structure function. In the present paper, the author report results from a numerical simulation of atmospheric turbulent convection in order to verify this theory. The simulation was based on a shell model which was deduced from simplified atmospheric convection equations. The numerical results agreed well with the theory prediction of scaling law from the first order to the eighth order. They also showed that the prediction of this theory was better than that given by the Kolmogorov＇s theory in 1941, log-normal, and β model theories.

Tumour mutational burden (TMB) has been retrospectively correlated with response to immune checkpoint blockade. We prospectively explored the association of high tissue TMB (tTMB-high) with outcomes in ten tumour-type-specific cohorts from the phase 2 KEYNOTE-158 study, which assessed the anti-PD-1 monoclonal antibody pembrolizumab in patients with selected, previously treated, advanced solid tumours. In the multi-cohort, open-label, non-randomised, phase 2 KEYNOTE-158 study, patients were enrolled from 81 academic facilities and community-based institutions across 21 countries in Africa, the Americas, Asia, and Europe. Eligible patients were aged 18 years or older, had a histologically or cytologically confirmed advanced (ie, unresectable or metastatic, or both) incurable solid tumour (eligible tumour types were anal, biliary, cervical, endometrial, mesothelioma, neuroendocrine, salivary, small-cell lung, thyroid, and vulvar), progression on or intolerance to one or more lines of standard therapy, had measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST; version 1.1) assessed by independent central radiological review, Eastern Cooperative Oncology Group performance status of 0 or 1, life expectancy of at least 3 months, adequate organ function, and a tumour sample for biomarker analysis. Participants were given pembrolizumab 200 mg intravenously every 3 weeks for up to 35 cycles. Tissue TMB (tTMB) was assessed in formalin-fixed paraffin-embedded tumour samples using the FoundationOne CDx assay (Foundation Medicine, Cambridge, MA, USA). The prespecified definition of tTMB-high status was at least 10 mutations per megabase. The primary endpoint was the proportion of patients with an objective response (complete or partial response) as per Response Evaluation Criteria in Solid Tumours (version 1.1) by independent central review. This prespecified analysis assessed the association between antitumour activity and tTMB in treated patients with evaluable tTMB data. Efficacy was assessed in all participants who received at least one dose of pembrolizumab, had evaluable tTMB data, and were enrolled at least 26 weeks before data cutoff (June 27, 2019), and safety was assessed in all participants who received at least one dose of pembrolizumab and had tTMB-high status. KEYNOTE-158 is registered at ClinicalTrials.gov, NCT02628067, and is ongoing. Between Jan 15, 2016, and June 25, 2019, 1073 patients were enrolled. 1066 participants were treated as of data cutoff (June 27, 2019), of whom 805 (76%) were evaluable for TMB, and 105 (13%) of 805 had tTMB-high status and were assessed for safety. 1050 (98%) of 1066 patients enrolled by at least 26 weeks before data cutoff, of whom 790 (75%) were evaluable for TMB and included in efficacy analyses. 102 (13%) of these 790 patients had tTMB-high status (≥10 mutations per megabase), and 688 (87%) patients had non-tTMB-high status (<10 mutations per megabase). Median study follow-up was 37·1 months (IQR 35·0–38·3). Objective responses were observed in 30 (29%; 95% CI 21–39) of 102 patients in the tTMB-high group and 43 (6%; 5–8) of 688 in the non-tTMB-high group. 11 (10%) of 105 patients had treatment-related serious adverse events. 16 (15%) participants had a grade 3–5 treatment-related adverse event, of which colitis was the only such adverse event that occurred in more than one patient (n=2). One patient had fatal pneumonia that was assessed by the investigator to be treatment related. tTMB-high status identifies a subgroup of patients who could have a robust tumour response to pembrolizumab monotherapy. tTMB could be a novel and useful predictive biomarker for response to pembrolizumab monotherapy in patients with previously treated recurrent or metastatic advanced solid tumours. Merck Sharp & Dohme Corp, a subsidiary of Merck & Co, Inc.

Biological ion channels have remarkable ion selectivity, permeability and rectification properties, but it is challenging to develop artificial analogues. Here, we report a metal–organic framework-based subnanochannel (MOFSNC) with heterogeneous structure and surface chemistry to achieve these properties. The asymmetrically structured MOFSNC can rapidly conduct K + , Na + and Li + in the subnanometre-to-nanometre channel direction, with conductivities up to three orders of magnitude higher than those of Ca 2+ and Mg 2+ , equivalent to a mono/divalent ion selectivity of 10 3 . Moreover, by varying the pH from 3 to 8 the ion selectivity can be tuned further by a factor of 10 2 to 10 4 . Theoretical simulations indicate that ion–carboxyl interactions substantially reduce the energy barrier for monovalent cations to pass through the MOFSNC, and thus lead to ultrahigh ion selectivity. These findings suggest ways to develop ion selective devices for efficient ion separation, energy reservation and power generation. Here, using an interfacial growth strategy, UiO-66 MOF nanocrystals are asymmetrically embedded into conical pores in a polymer membrane. These pores have a mono/divalent cation selectivity of 10 3 , which can be tuned by pH, and act as ionic rectifiers.

BackgroundDuring the outbreak of COVID-19, the national policy of home quarantine may affect the mental health of parents. However, few studies have investigated the mental health of parents during the COVID-19 pandemic.AimsTo investigate the depression, anxiety and stress of the students’ parents during the COVID-19 pandemic, and to explore the influence factors, especially the influence of social support and family-related factors.MethodsThe Generalised Anxiety Disorder-7, Patient Health Questionnaire-9, Perceived Stress Scale-10 and Social Support Rating Scale were applied to 1163 parents to measure the parents’ depression, anxiety, stress and social support.Results(1) The detection rates of depression and anxiety in parents were 6.1% and 4.0%. The depression, anxiety and perceived stress of parents in central China were significantly higher than those in non-central China. The anxiety of college students’ parents was lower than that of parents of the primary, middle and high school students. The depression, anxiety and perceived stress of parents with conflicts in the family were significantly higher than those with a harmonious family. Other factors that influence parents’ depression, anxiety and perceived stress include marital satisfaction, social support, parents’ history of mental illness and parenting style, etc. (2) The regression analysis results showed that perceived stress, social support, marital satisfaction, family conflicts, child’s learning stage as well as parents’ history of mental illness had significant effects on parents’ anxiety and depression.ConclusionDuring the COVID-19 pandemic, the mental health of parents was affected by a variety of factors. Good marital relationships, good social support, family harmony and parents without a history of mental illness may be protective factors for parents’ mental health, while perceived stress and child in middle or high school are risk factors for parents’ mental health.

Biological fluoride ion channels are sub-1-nanometer protein pores with ultrahigh F − conductivity and selectivity over other halogen ions. Developing synthetic F − channels with biological-level selectivity is highly desirable for ion separations such as water defluoridation, but it remains a great challenge. Here we report synthetic F − channels fabricated from zirconium-based metal-organic frameworks (MOFs), UiO-66-X (X = H, NH 2 , and N + (CH 3 ) 3 ). These MOFs are comprised of nanometer-sized cavities connected by sub-1-nanometer-sized windows and have specific F − binding sites along the channels, sharing some features of biological F − channels. UiO-66-X channels consistently show ultrahigh F − conductivity up to ~10 S m −1 , and ultrahigh F − /Cl − selectivity, from ~13 to ~240. Molecular dynamics simulations reveal that the ultrahigh F − conductivity and selectivity can be ascribed mainly to the high F − concentration in the UiO-66 channels, arising from specific interactions between F − ions and F − binding sites in the MOF channels. While biological fluoride ion channels display excellent F − conductivity and selectivity, designing synthetic analogues remains highly challenging. Here the authors show that zirconium-based metal–organic frameworks with F − binding sites and sub-1-nanometer channels exhibit ultrahigh F − conductivity and selectivity.

As one of the major cell organelles responsible for ATP production, it is important that neurons maintain mitochondria with structural and functional integrity; this is especially true for neurons with high metabolic requirements. When mitochondrial damage occurs, mitochondria are able to maintain a steady state of functioning through molecular and organellar quality control, thus ensuring neuronal function. And when mitochondrial quality control (MQC) fails, mitochondria mediate apoptosis. An apparently key molecule in MQC is the transcriptional coactivator peroxisome proliferator activated receptor γ coactivator-1α (PGC-1α). Recent findings have demonstrated that upregulation of PGC-1α expression in neurons can modulate MQC to prevent mitochondrial dysfunction in certain in vivo and in vitro aging or neurodegenerative encephalopathy models, such as Huntington’s disease, Alzheimer’s disease, and Parkinson’s disease. Because mitochondrial function and quality control disorders are the basis of pathogenesis in almost all neurodegenerative diseases (NDDs), the role of PGC-1α may make it a viable entry point for the treatment of such diseases. This review focuses on multi-level MQC in neurons, as well as the regulation of MQC by PGC-1α in these major NDDs.