A data-driven framework for learning hybrid dynamical systems.

The existing data-driven identification methods for hybrid dynamical systems such as sparse optimization are usually limited to parameter identification for coefficients of pre-defined candidate functions or composition of prescribed function forms, which depend on the prior knowledge of the dynamical models. In this work, we propose a novel data-driven framework to discover the hybrid dynamical systems from time series data, without any prior knowledge required of the systems. More specifically, we devise a dual-loop algorithm to peel off the data subject to each subsystem of the hybrid dynamical system. Then, we approximate the subsystems by iteratively training several residual networks and estimate the transition rules by training a fully connected neural network. Several prototypical examples are presented to demonstrate the effectiveness and accuracy of our method for hybrid models with various dimensions and structures. This method appears to be an effective tool for learning the evolutionary governing laws of hybrid dynamical systems from available data sets with wide applications.

Nerve Growth Factor is a Potential Treated Target in Tg(SOD1*G93A)1Gur Mice.

Nerve growth factor (NGF) is a protective factor of neural cells; the possible relationship between the NGF and the pathogenesis of amyotrophic lateral sclerosis (ALS) hasn't been completely known. In this study, we observed and analyzed the expression and distribution of NGF, as well as the possible relationship between the NGF expression and distribution and the neural cell death in both SOD1 wild-type (WT) and Tg(SOD1*G93A)1Gur (TG) mice applying the fluorescence immunohistochemistry method. The results showed that the expression and distribution of NGF in the anterior horn (AH), the lateral horn (LH), and the surrounding central canal (CC) significantly increased at the supper early stage of ALS (Pre-onset stage) and the early stage (Onset stage), but the NGF expression and distribution in the AH, the LH, and the surrounding CC significantly reduced at the progression stage. The astrocyte, neuron, and oligodendrocyte produced the NGF and the neural precursor cells (NPCs) produced the NGF. The neural cell death gradually increased accompanying with the reduction of NGF expression and distribution. Our data suggested that the NGF was a protective factor of neural cells, because the neural cells in the AH, the LH, and the surrounding CC produced more NGF at the supper early and early stage of ALS; moreover, the NPCs produced the NGF. It implied that the NGF exerted the protective effect of neural cells, prevented from the neural cell death and aroused the potential of self-repair in the development of ALS.

Estimation of numbers of mature and immature neutrophils in blood by a novel, rapid and simple technology.

Counting numbers of blood neutrophils is one of the most common laboratory tests in modern clinical medicine. In this report, we have tested the idea that immunoassay of major constituents of mature neutrophils might serve as proxy of cell counting and allow the development of rapid and simple point-of-care tests. The procedure may also allow for the estimate of the state of maturity of the circulating blood cells. Immunoassays for myeloperoxidase (MPO) and lactoferrin (LF) were used to measure the respective protein in whole blood extracts of 275 unselected hospitalized patient and in 51 healthy controls and leukemia patients of which eight were followed before, during and after remission treatment. MPO was correlated to neutrophil counts in the unselected hospitalized population (r = 0.95, p <.0001). Huge variations were seen in whole blood extracts of patients with AML with very high MPO/LF ratios in half of the AML patients and in all three patients with APL. In extracts from patients with ALL no difference was found in the ratio as compared to healthy persons. The monitoring of AML patients during remission treatment showed intriguing patterns one of which suggested the possibility to monitor the myelopoietic activity in the bone marrow during the recovery phase. We show a novel and easy technology to count mature neutrophils in blood and also to monitor myeloid cell maturity in the blood as well as myelopoietic activity in the bone marrow. The technology lends itself to the development of a rapid and simple point-of-care test.

Distribution Changes of Neural Precursor Cells in the Brain Stem of Tg(SOD1*G93A)1Gur Mice.

OBJECTIVES: The alteration of vimentin-containing cells (VCCs) proliferation, differentiation, and migration in the brain stem of amyotrophic lateral sclerosis (ALS)-like transgenic mice (Tg(SOD1*G93A)1Gur mice) (TG mice) and wild-type mice (WT mice) at the different disease stages of TG mice was studied in this study. The aims of this study were to investigate the change features of proliferation, differentiation, and migration of endogenous neural precursor cells (NPCs) and to explore the potential effects of NPCs on restoring degenerated neurons in ALS. METHODS: The proliferation, differentiation, and migration of VCCs in both different anatomic regions and neural cells of brain stem at the different stages including pre-onset (60-70 days), onset (90-100 days), and progression (120-130 days) stages of TG mice and in WT mice (control) were examined using the immunofluorescence technology. RESULTS: VCCs were mainly distributed in the around (peripheral) central canal (CC) and the nuclei of brain stem in adult WT mice. VCCs proliferated and differentiated into astrocytes and directionally migrated from the around CC to the nuclei of brain stem, and then to the ventral part of damaged regions in brain stem at the pre-onset, onset, and progression stages of TG mice. CONCLUSIONS: The data suggest that NPCs widely distributed in the brain stem of adult TG mice can differentiate into astrocytes and migrate into damaged brain regions. This response might be a potential mechanism to repair degenerated motor neurons and restore dysfunctional neural circuitry in ALS.

[Effects of end time of night feeding on the growth and development of infants/toddlers].

OBJECTIVE: To investigate the effects of end time of night feeding on body height, body weight, nutritional status, and prevalence rate of dental caries in children at the age of 30 months. METHODS: A total of 416 children who were born from January 2014 to September 2015 and had completed a physical examination as required were enrolled. During the physical examination performed at the age of 30 months, the comprehensive child care record and a self-made questionnaire were used. The children who continued to receive night feeding after the age of 6 months were enrolled as study group (n=269), and those for whom night feeding was ended at the age of 6 months were enrolled as control group (n=147). The two groups were compared in terms of body height, body weight, incidence rate of overweight/obesity, and prevalence rate of dental caries at the age of 30 months. RESULTS: Compared with the control group, the study group had a significantly lower body height (92.4±3.0 cm vs 93.3±2.8 cm; P<0.05), a significantly higher incidence rate of overweight/obesity (23.8% vs 12.2%; P<0.05), and a significantly higher prevalence rate of dental caries (14.9% vs 7.5%; P<0.05) at the age of 30 months. CONCLUSIONS: Night feeding continued after the age of 6 months can affect the growth and development of infants/toddlers, cause overnutrition, and increase the prevalence rate of dental caries.

Adiponectin induces CXCL1 secretion from cancer cells and promotes tumor angiogenesis by inducing stromal fibroblast senescence.

Adiponectin is an adipocyte-specific adipocytokine with proliferative and pro-angiogenic effects that regulates many biological processes, including immunity, insulin resistance, and inflammation. The oncogenic role of adiponectin has been implicated in several cancer types. Stromal cells within tumor contribute tumor growth and angiogenesis; however, it is not clear that how adiponectin regulates stromal cell-mediated tumorigenesis. In this study, using the tumor xenograft models, we demonstrated that tumor development was severely impaired in mouse subcutaneous cancer tissue and metastasis tumor tissue in adiponectin knockout mice. Our results indicated adiponectin deficiency resulted in decrease of blood vessel and stromal senescent fibroblasts in subcutaneous and metastasis tumor tissue. These observations were confirmed in vitro, in which co-cultured tumor cells and fibroblasts treated with adiponectin promoted ECs tube formation. A secretion of CXCL1 by adiponectin-treated tumor cells was observed during the process of inducing stromal fibroblast senescence. Furthermore, stromal cells senescence was through p53 and p16 pathways. Taken together, our results indicate that adiponectin promotes stromal cell senescence within invasive colon cancer contributing to angiogenesis and tumor growth in part through the production of CXCL1 and may serve as a therapeutic target for tumor patients. © 2015 Wiley Periodicals, Inc.

A Novel Event-Triggered Bipartite Consensus for PDE-Based Multiagent Systems With Switching Topologies and Antagonistic Interactions.

Unlike the traditional studies on multiagent systems (MASs), this article investigates a class of MASs with spatial properties, whose agents are modeled by partial differential equations (PDE), in addition, to make the model more comprehensive, the Markovian switching topology with partially unknown probability is taken into account. The purpose of this article is to achieve the bipartite consensus for the above PDE-based MASs. In fact, the consideration of spatial factors in MASs will exacerbate the network transmission pressure, to overcome this problem, a novel spatiotemporal event-triggered mechanism is developed. Compared with the existing event-triggered mechanism, the proposed one is not only time-dependent but also covers the influence of spatial variables on the trigger conditions, which helps to further reduce the triggering frequency. Finally, three examples are given to verify the validity of the conclusion we proposed.

The Human Phospholipase B-II Precursor (HPLBII-P) in Urine as a Novel Biomarker of Increased Glomerular Production or Permeability in Diabetes Mellitus?

Background: A previous report showed that the urine output of HPLBII-P in patients with diabetes mellitus and SARS-CoV-2 infection was increased as a sign of glomerular dysfunction. The aim of this report was to investigate the relation of the urine output of HPLBII-P to diabetes mellitus in two large community-based elderly populations, i.e., the ULSAM and PIVUS cohorts. Methods: HPLBII-P was measured by an ELISA in the urine of a community-based cohort of 839 men (ULSAM) collected at 77 years of age and in the urine of a community-based cohort of 75-year-old men, n = 387, and women, n = 401 (PIVUS). KIM-1, NGAL, and albumin were measured in urine and cathepsin S and cystatin C in serum. Results: HPLBII-P was significantly raised among males with diabetes in the ULSAM (p < 0.0001) and PIVUS cohorts (p ≤ 0.02), but not in the female cohort of PIVUS. In the female subpopulation of insulin-treated diabetes, HPLBII-P was raised (p = 0.02) as compared to women treated with oral antidiabetics only. In the ULSAM cohort, HPLBII-P was correlated to NGAL, KIM-1, and albumin in urine both in non-DM (all three biomarkers; p < 0.0001) and in DM (NGAL; p = 0.002, KIM-1; p = 0.02 and albumin; p = 0.01). Plasma glucose and HbA1c in blood showed correlations to U-HPLBII-P (r = 0.58, p < 0.001 and r = 0.42, p = 0.004, respectively). U-HPLBII-P and cathepsin S were correlated in the ULSAM group (r = 0.50, p < 0.001). No correlations were observed between U-HPLBII-P and serum creatinine or cystatin C. Conclusions: The urine measurement of HPLBII-P has the potential to become a novel and useful biomarker in the monitoring of glomerular activity in diabetes mellitus.

The Human Phospholipase B-II Precursor (HPLBII-P) in Urine as a Novel Biomarker of Glomerular Activity in COVID-19 and Diabetes Mellitus.

Background: The human phospholipase B-II precursor (HPLBII-P) was originally purified from white blood cells but is also found in other cellular structures, such as kidney glomeruli and tubuli. The objective of this report was to investigate the relationship of HPLBII-P in urine to acute kidney injury in patients with COVID-19. Methods: Urine was collected at admission from 132 patients with COVID-19 admitted to the intensive care units (ICUs) because of respiratory failure. HPLBII-P was measured using a sensitive ELISA. For comparison, human neutrophil lipocalin (HNL) was measured in urine, using the ELISA configured with the monoclonal antibody 763/8F, as a sign of tubular affection in addition to routine biomarkers of kidney disease. Results: Overall, the concentrations of urinary HPLBII-P were almost 3-fold higher in patients with COVID-19 compared to healthy controls (p < 0.0001) and with significantly higher concentrations even in patients with COVID-19 without signs of acute kidney injury (AKI) (p < 0.001). HPLBII-P was further increased in patients with AKI (p < 0.02). HPLBII-P was significantly increased in patients with diabetes mellitus (p = 0.0008) and correlated to plasma glucose (r = 0.29, p = 0.001) and urine albumin concentrations (r = 0.55, p < 0.001). Conclusions: Urine concentrations of HPLBII-P are highly raised in the urine of patients with COVID-19 and relate to AKI and diabetes mellitus. HPLBII-P may reflect glomerular injury and/or increased glomerular cell activity in SARS-CoV-2 infections.

Neural Preassigned Performance Control for State-Constrained Nonlinear Systems Subject to Disturbances.

This article addresses the finite-time neural predefined performance control (PPC) issue for state-constrained nonlinear systems (NSs) with exogenous disturbances. By integrating the predefined-time performance function (PTPF) and the conventional barrier Lyapunov function (BLF), a new set of time-varying BLFs is designed to constrain the error variables. This establishes conditions for satisfying full-state constraints while ensuring that the tracking error meets the predefined performance indicators (PPIs) within a predefined time. Additionally, the incorporation of the nonlinear disturbance observer technique (NDOT) in the control design significantly enhances the ability of the system to reject disturbances and improves overall robustness. Leveraging recursive design based on dynamic surface control (DSC), a finite-time neural adaptive PPC strategy is devised to ensure that the closed-loop system is semi-globally practically finite-time stable (SPFS) and achieves the desired PPIs. Finally, the simulation results of two practical examples validate the efficacy and viability of the proposed approach.

LILRB2 promotes immune escape in breast cancer cells via enhanced HLA-A degradation.

PURPOSE: Increased expression of leukocyte immunoglobulin-like receptor subfamily B member 2 (LILRB2) is associated with immune evasion in breast cancer (BC). The aim of this study to elucidate the role of LILRB2 in BC progression. METHODS: LILRB2 expression in tumor tissues was detected by immunohistochemical staining. Human leukocyte antigen A (HLA-A) expression in BC cells was detected by Western blotting, and HLA-A ubiquitination was detected by immunoprecipitation and histidine pulldown assay. An in-situ tumor model was established in nude BALB/c mice to verify the role of LILRB2 in immune escape. Finally, the functions and potential mechanisms of LILRB2 in BC progression were explored using in silico data. RESULTS: LILRB2 was upregulated in BC tissues and cells, and correlated positively with poor prognosis. LILRB2 promoted BC progression by downregulating HLA-A expression. Mechanistically, LILRB2 facilitates the ubiquitination and subsequent degradation of HLA-A by promoting the interaction between the ubiquitin ligase membrane-associated ring finger protein 9 (MARCH9) and HLA-A. In syngeneic graft mouse models, LILRB2-expressing BC cells evaded CD8 + T cells and inhibited the secretion of cytokines by the cytotoxic CD8 + T cells. CONCLUSION: LILRB2 downregulates HLA-A to promote immune evasion in BC cells and is a promising new target for BC treatment.

Association of plasma neutrophil gelatinase-associated lipocalin (NGAL) with sepsis and acute kidney dysfunction.

OBJECTIVE: Neutrophil gelatinase-associated lipocalin (NGAL) is secreted by injured kidney cells as well as by activated neutrophils in response to bacterial infections. We assessed the influence of acute renal dysfunction on the association between plasma NGAL and sepsis. METHODS: NGAL was measured daily in 138 critically ill patients. Simultaneous recordings of sepsis status and fluctuations in renal function were made. RESULTS: Elevated NGAL was associated with sepsis independent of level of acute renal dysfunction. A cut-off value of 98 ng/mL distinguished sepsis from systemic inflammation with high sensitivity (0.77) and specificity (0.79). CONCLUSIONS: Plasma NGAL can help clinicians to identify bacterial infections in critically ill patients.

Adaptive Event-Triggered Finite-Time Control for Uncertain Time Delay Nonlinear System.

In this article, adaptive event-triggered finite-time control is explored for uncertain nonlinear systems with time delay. First, to handle the time-varying state delays, the Lyapunov-Krasovskii function is used. Fuzzy-logic systems are used to deal with the unknown nonlinearities of the system. Notice that compared to the reporting achievements, our proposed virtual control laws are derivable by using the novel switch function, which avoids "singularity hindrance" problem. Moreover, the dynamic event-triggered controller is designed to reduce the communication pressure and we prove that the controller is Zeno free. Our proposed control strategy ensures that the tracking error is arbitrarily small in finite time and all variables of the closed-loop system remain bounded. Finally, to show the effectiveness of our control strategy, the simulation results are given.

Asynchronous Resilent State Estimation of Switched Fuzzy Systems With Multiple State Impulsive Jumps.

This work researches the resilent mixed H∞ and energy-to-peak filter design problem of switched Takagi-Sugeno (T-S) fuzzy systems with asynchronous switching and multiple state impulsive jumps. The novelties include three points. First, a novel mixed H∞ and energy-to-peak performance index is proposed, which covers the H∞ performance index and energy-to-peak performance index as special cases. Second, in addition to designing the switching filters, the filter state jump rules are constructed at filter switching instants. Finally, both system states and filter states jump in a asynchronous manner. The switching law is devised through the mode-dependent average dwell time (MDADT) approach. A new type of Lyapunov-like functionals is constructed, which will increase when the subsystem is running with its mismatched filter and jump while the subsystem or the filter is switching. Then, new conditions are deduced to ensure the filtering error systems with multiple state impulsive jumps to be asymptotically stable with a mixed H∞ and energy-to-peak performance level. Filter design conditions expressing as linear matrix inequality (LMI) are obtained. Finally, the effectiveness of the derived results is illustrated by two examples.

Event-Triggered Adaptive Output-Feedback Control for Nonlinearly Parameterized Uncertain Systems With Quantization and Input Delay.

An output-feedback-based event-triggered control issue of a class of uncertain nonlinear systems considering state quantization and input delay is investigated. In this study, by constructing the state observer and adaptive estimation function, a discrete adaptive control scheme is designed based on the dynamic sampled and quantized mechanism. With the aid of the Lyapunov-Krasovskii functional method and a stability criterion, the global stability of the time-delay nonlinear systems is ensured. Additionally, the Zeno behavior will not happen in the event-triggering. Finally, a numerical example and a practical example are presented to verify the effectiveness of the designed discrete control algorithm with input time-varying delay.

Pinning Controller Design for Set Reachability of State-Dependent Impulsive Boolean Networks.

Considered the stimulation of tumor necrosis factor as an impulsive control, an apoptosis network is modeled as a state-dependent impulsive Boolean network (SDIBN). Making cell death normally means driving the trajectory of an apoptosis network out of states that indicate cell survival. To achieve the goal, this article focuses on the pinning controller design for set reachability of SDIBNs. To begin with, the definitions of reachability and set reachability are introduced, and their relation is illustrated. For judging whether the trajectory of an SDIBN leaves undesirable states, a necessary and sufficient condition is presented according to the criteria for the set reachability. In addition, a series of algorithms is provided to find all possible sets of pinning nodes for the set reachability. Note that attractors containing in all undesirable states are studied to make SDIBNs set reachable via controlling the smallest states. For the purpose of determining pinning nodes for one-step set reachability, the Hamming distance is presented under scalar forms of states. Pinning nodes with the smallest cardinality for the set reachability are derived by deleting some redundant nodes. Compared with the existing results, the state feedback gain can be obtained without solving logical matrix equations. The computation complexity of the proposed approach is lower than that of the existing methods. Moreover, the method of designing pinning controllers is used to discuss apoptosis networks. The experimental result shows that apoptosis networks depart from undesirable states by controlling only one node.

Event-Triggered Distributed Stochastic Mirror Descent for Convex Optimization.

This article is concerned with the distributed convex constrained optimization over a time-varying multiagent network in the non-Euclidean sense, where the bandwidth limitation of the network is considered. To save the network resources so as to reduce the communication costs, we apply an event-triggered strategy (ETS) in the information interaction of all the agents over the network. Then, an event-triggered distributed stochastic mirror descent (ET-DSMD) algorithm, which utilizes the Bregman divergence as the distance-measuring function, is presented to investigate the multiagent optimization problem subject to a convex constraint set. Moreover, we also analyze the convergence of the developed ET-DSMD algorithm. An upper bound for the convergence result of each agent is established, which is dependent on the trigger threshold. It shows that a sublinear upper bound can be guaranteed if the trigger threshold converges to zero as time goes to infinity. Finally, a distributed logistic regression example is provided to prove the feasibility of the developed ET-DSMD algorithm.

Effectiveness and safety of anlotinib with or without S-1 in the treatment of patients with advanced hepatocellular carcinoma in a Chinese population: a prospective, phase 2 study.

BACKGROUND: The aim of the study was to observe the safety and efficacy of anlotinib (ANL) alone or combined with S-1 in the first-line treatment of advanced hepatocellular carcinoma (HCC). PATIENTS AND METHODS: Fifty-four patients with untreated advanced HCC who could not be resected were randomly divided into the ANL group (n = 27) and ANL+S-1 group (n = 27). The ANL group was given 10 mg ANL orally once a day for 14 consecutive days, stopped for 1 week, and repeated every 21 days. The ANL+S-1 group was given 10 mg ANL once a day orally and 40 mg S-1 twice a day orally for 14 consecutive days, stopped for 1 week, repeated every 21 days. All patients were treated until the disease progressed or toxicity became unacceptable. For patients who could not tolerate adverse reactions, the ANL dose should be reduced to 8 mg per day. CT or MRI was reviewed every 6 weeks to evaluate the efficacy. RESULTS: A total of 44 patients were included in the results analysis, including 22 patients in the ANL group and 22 patients in the ANL+S-1 group. In the ANL group, the objective response rate (ORR) was 4.5% (1/22), the disease control rate (DCR) was 77.3% (17/22), the median progression-free survival (PFS) was 4.2 months (95% CI: 3.6-6.0) and the median overall survival (mOS) was 7.0 months (95% CI: 6.3-9.0). In the ANL+S-1 group, the ORR was 18.2% (4/22), the DCR was 59.1% (13/22), the median PFS was 4.0 months (95% CI: 3.6-5.4) and the mOS was 6.0 months (95% CI: 5.5-7.4). There was no significant difference in ORR (p = 0.345) or DCR (p = 0.195) between the two groups. Adverse reactions were mainly hypertension, anorexia, fatigue, liver transaminase heightened and hand and foot skin reaction. CONCLUSIONS: ANL monotherapy was effective in the treatment of advanced HCC, and adverse reactions have been able to tolerated.

BiOCl Heterojunction photocatalyst: Construction, photocatalytic performance, and applications.

BiOCl semiconductors have attracted extensive amounts of attention and have substantial potential in alleviating energy shortages, improving sterilization performance, and solving environmental issues. To improve the optical quantum efficiency of layered BiOCl, the lifetimes of photogenerated electron-hole pairs, and BiOCl reduction capacity. During the past decade, researchers have designed many effective methods to weaken the effects of these limitations, and heterojunction construction is regarded as one of the most promising strategies. In this paper, BiOCl heterojunction photocatalysts designed and synthesized by various research groups in recent years were reviewed, and their photocatalytic properties were tested. Among them, direct Z-scheme and S-scheme photocatalysts have high redox potentials and intense redox capabilities. Hence, they exhibit excellent photocatalytic activity. Furthermore, the applications of BiOCl heterojunctions for pollutant degradation, CO2 reduction, water splitting, N2 fixation, organic synthesis, and tumor ablation are also reviewed. Finally, we summarize research on the BiOCl heterojunctions and put forth new insights on overcoming their present limitations.