In this technical note, we consider adaptive control of single input uncertain nonlinear systems in the presence of input saturation and unknown external disturbance. By using backstepping ...approaches, two new robust adaptive control algorithms are developed by introducing a well defined smooth function and using a Nussbaum function. The Nussbaum function is introduced to compensate for the nonlinear term arising from the input saturation. Unlike some existing control schemes for systems with input saturation, the developed controllers do not require assumptions on the uncertain parameters within a known compact set and a priori knowledge on the bound of the external disturbance. Besides showing global stability, transient performance is also established and can be adjusted by tuning certain design parameters.
•The consistency definition and the goal programming model proposed by Liu, Zhang, and Wang (2012) are technically wrong.•New transitivity conditions are put forward to correct errors in Liu et al. ...(2012).•A two-stage goal programming approach is developed to estimate missing values.
In a recently published paper by Liu et al. Liu, F., Zhang, W.G., Wang, Z.X. (2012). A goal programming model for incomplete interval multiplicative preference relations and its application in group decision-making. European Journal of Operational Research 218, 747–754, two equations are introduced to define consistency of incomplete interval multiplicative preference relations (IMPRs) and employed to develop a goal programming model for estimating missing values. This note illustrates that such consistency definition and estimation model are technically incorrect. New transitivity conditions are proposed to define consistent IMPRs, and a two-stage goal programming approach is devised to estimate missing values for incomplete IMPRs.
Effective treatment options are limited for patients with acute myeloid leukemia (AML) who cannot tolerate intensive chemotherapy. Adults age ≥18 years with newly diagnosed AML ineligible for ...intensive chemotherapy were enrolled in this international phase 3 randomized double-blind placebo-controlled trial. Patients (N = 211) were randomized 2:1 to venetoclax (n = 143) or placebo (n = 68) in 28-day cycles, plus low-dose cytarabine (LDAC) on days 1 to 10. Primary end point was overall survival (OS); secondary end points included response rate, transfusion independence, and event-free survival. Median age was 76 years (range, 36-93 years), 38% had secondary AML, and 20% had received prior hypomethylating agent treatment. Planned primary analysis showed a 25% reduction in risk of death with venetoclax plus LDAC vs LDAC alone (hazard ratio HR, 0.75; 95% confidence interval CI, 0.52-1.07; P = .11), although not statistically significant; median OS was 7.2 vs 4.1 months, respectively. Unplanned analysis with additional 6-month follow-up demonstrated median OS of 8.4 months for the venetoclax arm (HR, 0.70; 95% CI, 0.50-0.98; P = .04). Complete remission (CR) plus CR with incomplete blood count recovery rates were 48% and 13% for venetoclax plus LDAC and LDAC alone, respectively. Key grade ≥3 adverse events (venetoclax vs LDAC alone) were febrile neutropenia (32% vs 29%), neutropenia (47% vs 16%), and thrombocytopenia (45% vs 37%). Venetoclax plus LDAC demonstrates clinically meaningful improvement in remission rate and OS vs LDAC alone, with a manageable safety profile. Results confirm venetoclax plus LDAC as an important frontline treatment for AML patients unfit for intensive chemotherapy. This trial was registered at www.clinicaltrials.gov as #NCT03069352.
Key points
α2δ‐1 is upregulated, promoting the interaction with NMDA receptors (NMDARs), in the hypothalamus in a rat model of hypertension.
The prevalence of α2δ‐1–bound NMDARs at synaptic sites in ...the hypothalamus is increased in hypertensive animals.
α2δ‐1 is essential for the increased presynaptic and postsynaptic NMDAR activity of hypothalamic neurons in hypertension.
α2δ‐1–bound NMDARs in the hypothalamus are critically involved in augmented sympathetic outflow in hypertensive animals.
Increased glutamate NMDA receptor (NMDAR) activity in the paraventricular nucleus (PVN) of the hypothalamus leads to augmented sympathetic outflow in hypertension. However, the molecular mechanisms underlying this effect remain unclear. α2δ‐1, previously considered to be a voltage‐activated calcium channel subunit, is a newly discovered powerful regulator of NMDARs. In the present study, we determined the role of α2δ‐1 in regulating synaptic NMDAR activity of rostral ventrolateral medulla (RVLM)‐projecting PVN neurons in spontaneously hypertensive rats (SHRs). We show that the protein levels of α2δ‐1 and NMDARs in synaptosomes and the α2δ‐1–NMDAR complexes in the hypothalamus were substantially higher in SHRs than in normotensive control rats. The basal amplitude of evoked NMDAR currents and NMDAR‐mediated synaptic glutamate release in RVLM‐projecting PVN neurons were significantly increased in SHRs. Strikingly, inhibiting α2δ‐1 activity with gabapentin or disrupting the α2δ‐1–NMDAR association with an α2δ‐1 C‐terminus peptide completely normalized the amplitude of evoked NMDAR currents and NMDAR‐mediated synaptic glutamate release in RVLM‐projecting PVN neurons in SHRs. In addition, microinjection of the α2δ‐1 C‐terminus peptide into the PVN substantially reduced arterial blood pressure and renal sympathetic nerve discharges in SHRs. Our findings indicate that α2δ‐1–bound NMDARs in the PVN are required for the potentiated presynaptic and postsynaptic NMDAR activity of PVN presympathetic neurons and for the elevated sympathetic outflow in hypertension. α2δ‐1–bound NMDARs may be an opportune target for treating neurogenic hypertension.
Key points
α2δ‐1 is upregulated, promoting the interaction with NMDA receptors (NMDARs), in the hypothalamus in a rat model of hypertension.
The prevalence of α2δ‐1–bound NMDARs at synaptic sites in the hypothalamus is increased in hypertensive animals.
α2δ‐1 is essential for the increased presynaptic and postsynaptic NMDAR activity of hypothalamic neurons in hypertension.
α2δ‐1–bound NMDARs in the hypothalamus are critically involved in augmented sympathetic outflow in hypertensive animals.
In this paper, we propose a new totally decentralized adaptive output tracking scheme for a class of nonlinear interconnected systems by using a backstepping approach. In the design, a smooth ...function is introduced to compensate for the effects of interactions from other subsystems. It is shown that the designed local adaptive controllers can ensure all the signals in the closed loop system are bounded. A root mean square type of bound is obtained for the tracking error as a function of design parameters. This implies that the transient tracking error performance can be adjusted by choosing suitable design parameters.
We describe pLink 2, a search engine with higher speed and reliability for proteome-scale identification of cross-linked peptides. With a two-stage open search strategy facilitated by fragment ...indexing, pLink 2 is ~40 times faster than pLink 1 and 3~10 times faster than Kojak. Furthermore, using simulated datasets, synthetic datasets,
N metabolically labeled datasets, and entrapment databases, four analysis methods were designed to evaluate the credibility of ten state-of-the-art search engines. This systematic evaluation shows that pLink 2 outperforms these methods in precision and sensitivity, especially at proteome scales. Lastly, re-analysis of four published proteome-scale cross-linking datasets with pLink 2 required only a fraction of the time used by pLink 1, with up to 27% more cross-linked residue pairs identified. pLink 2 is therefore an efficient and reliable tool for cross-linking mass spectrometry analysis, and the systematic evaluation methods described here will be useful for future software development.
Inflammatory injury plays a critical role in intracerebral hemorrhage (ICH)-induced neurological deficits; however, the signaling pathways are not apparent by which the upstream cellular events ...trigger innate immune and inflammatory responses that contribute to neurological impairments. Toll-like receptor 4 (TLR4) plays a role in inflammatory damage caused by brain disorders.
In this study, we investigate the role of TLR4 signaling in ICH-induced inflammation. In the ICH model, a significant upregulation of TLR4 expression in reactive microglia has been demonstrated using real-time RT-PCR. Activation of microglia was detected by immunohistochemistry, cytokines were measured by ELISA, MyD88, TRIF and NF-κB were measured by Western blot and EMSA, animal behavior was evaluated by animal behavioristics.
Compared to WT mice, TLR4(-/-) mice had restrained ICH-induced brain damage showing in reduced cerebral edema and lower neurological deficit scores. Quantification of cytokines including IL-6, TNF-α and IL-1β and assessment of macrophage infiltration in perihematoma tissues from TLR4(-/-), MyD88(-/-) and TRIF(-/-) mice showed attenuated inflammatory damage after ICH. TLR4(-/-) mice also exhibited reduced MyD88 and TRIF expression which was accompanied by decreased NF-κB activity. This suggests that after ICH both MyD88 and TRIF pathways might be involved in TLR4-mediated inflammatory injury possibly via NF-κB activation. Exogenous hemin administration significantly increased TLR4 expression and microglial activation in cultures and also exacerbated brain injury in WT mice but not in TLR4(-/-) mice. Anti-TLR4 antibody administration suppressed hemin-induced microglial activation in cultures and in the mice model of ICH.
Our findings suggest that heme potentiates microglial activation via TLR4, in turn inducing NF-κB activation via the MyD88/TRIF signaling pathway, and ultimately increasing cytokine expression and inflammatory injury in ICH. Targeting TLR4 signaling may be a promising therapeutic strategy for ICH.
Two novel isostructural lanthanide metal–organic frameworks (Ln-MOFs), Ln2(BPDC)(BDC)2(H2O)2 n (Ln = Eu (1) and Tb (2)), have been successfully synthesized via a mixed ligand approach using ...2,2′-bipyridine-3,3′-dicarboxylic acid (H2BPDC) and 1,4-benzenedicarboxylic acid (H2BDC) under hydrothermal conditions. Structural analysis shows that two lanthanide ions are 4-fold linked by two κ1-κ1-μ2 carboxylates from BDC2– and the other two κ2-κ1-μ2 carboxylates from BPDC2– to form a binuclear core. The binuclear units are further connected by BDC2– and BPDC2– to build a three-dimensional framework possessing tfz-d topology with the short (Schläfli) vertex symbol {43}2{46·618·84}. Moreover, isostructural doped Ln-MOFs Eu2x Tb2(1–x)(BPDC)(BDC)2(H2O)2 n (x = 0.1 (1a), 0.3 (1b), 0.5 (1c), 0.7 (1d), and 0.9 (1e)) were also successfully synthesized. Thermal gravimetric analyses (TGA) reveal high thermal stability of these Ln-MOFs. Luminescent measurements indicate that the characteristic sharp emission bands of Eu3+ and Tb3+ ions are simultaneously observed in 1a–e. Further luminescent studies reveal that 1, 2, and 1a not only display a high-sensitivity sensing function with respect to fluoride but also exhibit significant solvent-dependent luminescent response to small-molecule pollutants, such as formaldehyde, acetonitrile, and acetone.
•Illustrate defects of the popularly used interval weight additive normalization model for characterizing a group of equivalent0, 1-valued interval weight vectors.•Introduce a novel framework of ...multiplicatively normalized interval fuzzy weights (MNIFWs).•Use MNIFWs to define multiplicative consistency of interval fuzzy preference relations (IFPRs) and propose significant properties for consistent IFPRs.•Establish two goal programming (GP) models to derive optimal MNIFWs in analytic form from multiplicatively consistent IFPRs.•Develop two visualized computation formulas to obtain approximate-solution-based MNIFWs from any IFPR.
This paper focuses on how to find an analytic solution of optimal interval weights from consistent interval fuzzy preference relations (IFPRs) and obtain approximate-solution-based interval weights in analytic form from inconsistent IFPRs. The paper first analyzes the popularly used interval weight additive normalization model and illustrates its drawbacks on the existence and uniqueness for characterizing 0, 1-valued interval weights obtained from IFPRs. By examining equivalency of 0, 1-valued interval weight vectors, a novel framework of multiplicatively normalized interval fuzzy weights (MNIFWs) is then proposed and used to define multiplicatively consistent IFPRs. The paper presents significant properties for multiplicatively consistent IFPRs and their associated MNIFWs. These properties are subsequently used to establish two goal programming (GP) models for obtaining optimal MNIFWs from consistent IFPRs. By the Lagrangian multiplier method, analytic solutions of the two GP models are found for consistent IFPRs. The paper further devises a two-step procedure for deriving approximate-solution-based MNIFWs in analytic form from inconsistent IFPRs. Two visualized computation formulas are developed to determine the left and right bounds of approximate-solution-based MNIFWs of any IFPR. The paper shows that this approximate solution is an optimal solution if an IFPR is multiplicatively consistent. Three numerical examples including three IFPRs and comparative analyses are offered to demonstrate rationality and validity of the developed model.
The authors examined conditions under which teams' educational specialization heterogeneity was positively related to team creativity. Using a sample of 75 research and development teams, the authors ...theorized and found that transformational leadership and educational specialization heterogeneity interacted to affect team creativity in such a way that when transformational leadership was high, teams with greater educational specialization heterogeneity exhibited greater team creativity. In addition, teams' creative efficacy mediated this moderated relationship among educational specialization heterogeneity, transformational leadership, and team creativity. The authors discuss the implications of these results for research and practice.
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