Platelet-derived growth factor-BB (PDGF-BB)/platelet-derived growth factor receptor-β (PDGFR-β) pathway is conventionally considered as an important pathway to promote osteogenesis; however, recent ...study suggested its role during osteogenesis to be controversial. Regarding the differential functions of this pathway during 3 stages of bone healing, we hypothesized that temporal inhibition of PDGF-BB/PDGFR-β pathway could shift the proliferation/differentiation balance of skeletal stem and progenitor cells, toward osteogenic lineage, which leads to improved bone regeneration. We first validated that inhibition of PDGFR-β at late stage of osteogenic induction effectively enhanced differentiation toward osteoblasts. This effect was also replicated in vivo by showing accelerated bone formation when block PDGFR-β pathway at late stage of critical bone defect healing mediated using biomaterials. Further, we found that such PDGFR-β inhibitor-initiated bone healing was also effective in the absence of scaffold implantation when administrated intraperitoneally. Mechanistically, timely inhibition of PDGFR-β blocked extracellular regulated protein kinase 1/2 pathway, which shift proliferation/differentiation balance of skeletal stem and progenitor cell to osteogenic lineage by upregulating osteogenesis-related products of Smad to induce osteogenesis. This study offered updated understanding of the use of PDGFR-β pathway and provides new insight routes of action and novel therapeutic methods in the field of bone repair.
Mach-Zehnder (MZ) modulators are widely used in optical transmitters to generate high-speed optical signals. With electronic dispersion compensation (EDC), the driving signals to MZ modulators change ...from digital to analog, or continuous waveforms. Consequently, there is signal degradation from their sinusoidal transfer curves. In this paper, we theoretically and numerically investigate the signal degradation in optical transmitters using MZ modulators in the presence of EDC. We show that the temporal waveforms follow the Gaussian distribution when the EDC is large, and therefore, the modulation index needs to be optimized between the output SNR and the excess insertion loss of MZ modulators. With varying modulation index, we quantify the output SNR and excess insertion loss of optical IQ modulators that consist of two parallel MZ modulators. The calculations are also extended to the scenarios where the sinusoidal transfer curves are compensated for. All the analytical results are verified in a simulation of QPSK transmissions, and they are useful for finding an optimized modulation index for a tradeoff between the output SNR and excess insertion loss.
Detrital zircon U-Pb and muscovite 40Ar/39Ar dating are useful tools for investigating sediment provenance and regional tectonic histories. However, the two types of data from same sample do not ...necessarily give consistent results. Here, we compare published detrital muscovite 40Ar/39Ar and zircon U-Pb ages of modern sands from the Yangtze River to reveal potential factors controlling differences in their provenance age signals. Detrital muscovite 40Ar/39Ar ages of the major tributaries and main trunk suggest that the Dadu River is a dominant sediment contributor to the lower Yangtze. However, detrital zircon data suggest that the Yalong, Dadu, and Min rivers are the most important sediment suppliers. This difference could be caused by combined effects of lower reaches dilution, laser spot location on zircons and difference in closure temperature and durability between muscovite and zircon. The bias caused by sediment laser spot targeting a core or rim of zircon and zircon reworking should be considered in provenance studies.
This article presents a novel force‐sensor‐less method for the estimation of external forces for a general class of second‐order robotic systems. The method is based on the integral sliding mode ...observer (ISMO) which serves as a second‐order differentiator for the position measurement of the system. As a result, the system states and disturbance are estimated without explicitly using force and velocity measurements. To apply the ISMO to the general second‐order systems, a proper assumption is proposed to address their nonlinearity and discontinuity. The boundary‐layer method is applied to ensure that the virtual inputs of the observer are continuous such that the chattering phenomenon is attenuated. A Lyapunov‐based method is used to analyze the influence of the boundary layers on the convergence of the state‐ and disturbance‐estimation errors. This influence, mainly determined by the boundary‐layer scalars, is given in analytical forms as a reference for parameter selection. The method is evaluated by numerical simulation on a robot manipulator system and compared with a conventional sliding mode observer (SMO). The validation of the performance of the continuous ISMO indicates its generalizability to general second‐order robotic systems. Also, the advantage of continuous ISMO over the conventional SMO is reflected by its small estimation errors and superior responsiveness. In general, the proposed method in this paper may interest those who are seeking solutions for haptic robotic tasks without using force sensors.
In this note, we develop an adaptive observer for a class of nonlinear systems with switched unknown parameters to estimate the states and parameters simultaneously. The main challenge lies in how to ...eliminate the disturbance effect of zero-input responses caused by the switching on the parameter estimation. These responses depend on the unknown states at switching instants (SASI) and constitute an additive disturbance to the parameter estimation, which obstructs parameter convergence to zero. Our solution is to treat the zero-input responses as excitations instead of disturbances. This is realized by first augmenting the system parameter with the SASI and then developing an estimator for the augmented parameter using the dynamic regression extension and mixing (DREM) technique. Thanks to its property of element-wise parameter adaptation, the system parameter estimation is decoupled from the SASI. As a result, the estimation errors of system states and parameters converge to zero asymptotically. Furthermore, the robustness of the proposed adaptive observer is guaranteed in the presence of disturbances and noise. A numerical example validates the effectiveness of the proposed approach.
Observer-based methods are widely used to estimate the disturbances of different dynamic systems. However, a drawback of the conventional disturbance observers is that they all assume persistent ...excitation (PE) of the systems. As a result, they may lead to poor estimation precision when PE is not ensured, for instance, when the disturbance gain of the system is close to the singularity. In this paper, we propose a novel disturbance observer based on concurrent learning (CL) with time-variant history stacks, which ensures high estimation precision even in PE-free cases. The disturbance observer is designed in both continuous and discrete time. The estimation errors of the proposed method are proved to converge to a bounded set using the Lyapunov method. A history-sample-selection procedure is proposed to reduce the estimation error caused by the accumulation of old history samples. A simulation study on epidemic control shows that the proposed method produces higher estimation precision than the conventional disturbance observer when PE is not satisfied. This justifies the correctness of the proposed CL-based disturbance observer and verifies its applicability to solving practical problems.
Intervertebral disc degeneration (IDD) is a major cause of low back pain (LBP), and effective therapies are still lacking. Previous studies reported that mitochondrial dysfunction contributes to ...apoptosis, and urolithin A (UA) specifically induces mitophagy. Herein, we aimed to investigate the protective effect of UA-induced mitophagy on tert-butyl hydroperoxide (TBHP)-induced apoptosis in nucleus pulposus (NP) cells in vitro and a rat model of IDD in vivo. Mitochondrial function, apoptosis, and mitophagy were measured in UA-treated NP cells by western blotting and immunofluorescence; the therapeutic effects of UA on IDD were assessed in rats with puncture-induced IDD. The results showed that UA could activate mitophagy in primary NP cells, and UA treatment inhibited TBHP-induced mitochondrial dysfunction and the intrinsic apoptosis pathway. Mechanistically, we revealed that UA promoted mitophagy by activating AMPK signaling in TBHP-induced NP cells. In vivo, UA was shown to effectively alleviate the progression of puncture-induced IDD in rats. Taken together, our results suggest that UA could be a novel and effective therapeutic strategy for IDD.
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•Urolithin A could induce mitophagy in primary NP cells.•Urolithin A attenuated TBHP-induced apoptosis and mitochondrial dysfunction in NP cells by activation of mitophagy.•The protective effects of Urolithin A both in vitro and in vivo were involved in AMPK activation.
In this paper the robust optimal control of deterministic information epidemics is inspected taking into consideration the noisy transition rates. Distinct from conventional works, the heterogeneous ...susceptible–infected–susceptible (SIS) model is adopted where both the heterogeneities in the network topology and the individual diversity are considered. In light of the commonly existing noise in the transition processes, we address the robust optimal control problem aiming at maximizing the spreading performance at the finite time instant given a fixed budget. By using the distribution analysis techniques, the inspected problem is transformed to a constrained optimal control problem and solved by the Pontryagin Maximum Principle (PMP). A novel approach combining the forward–backward sweep method and the secant method is proposed to efficiently reduce the computation burden. The performance of the robust optimal control as well as the influence of the parameters is examined by numerical experiments in real social networks.
•Robust optimal control for information epidemics is addressed for the first time.•Heterogeneities in both network structure and transition processes are considered.•Computationally cheap algorithms is provided and tested in real networks.
The ore-forming fluids were ultimately derived from low-δ18O meteoric waters. The ore-forming fluids leached 34S-rich gypsum, 11B-borate, sodium chloride and other salts in the evaporites of the ...Liaohe Group, which made the ore-forming hydrothermal fluids slightly alkaline and weakly oxidized. Some of this silica reacted with metamorphosed clay minerals in the wall rocks to form chlorite, garnet, tremolite, and biotite. Some of silica migrated and, as the temperature decreased, precipitated in veins or as aggregates around the high-grade iron ores. Most iron was enriched (semi-) in situ and this formed the high-grade iron ores. A small amount of “iron activation–reprecipitation” developed high-grade iron veins.
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•The Gongchangling high-grade magnetite ores were formed by Paleoproterozoic hydrothermal replacement of BIFs.•The ore-forming hydrothermal fluids leached soluble salts from evaporites of the Liaohe Group.•Desilicification and Fe enrichment was the primary mineralization mechanism of the Gongchangling high-grade iron ores.
The Gongchangling iron deposit in North China hosts abundant high-grade (>50 wt% total Fe) magnetite ores and represents one of the largest BIF-hosted magnetite deposits worldwide. These high-grade magnetite ores are generally accepted to be formed by replacement of banded iron formation (BIF) (∼30 wt% total Fe), but the mechanism of iron enrichment remains controversial. Here we report new O–S–B isotope data of BIFs, high-grade iron ores, and related altered wall rocks, from the Gongchangling iron deposit, together with the geological and geochronological data to constrain the formation of the high-grade iron ores, and proposed new genetic model. The high-grade iron ores have positive δ56Fe and negative δ30Si values, similar to the BIFs, whereas the δ18O values of the high-grade iron ores and altered wall rocks are significantly lower than those of the BIFs. The δ34S values of pyrite from the high-grade iron ores are much higher than those of the BIFs. The δ11B values of tourmaline in the altered wall rocks of the high-grade iron ores are anomalously high, which is distinct from those of the BIFs and wall rocks, but similar to those of the evaporites from the Liaohe Group. At ca. 1.85 Ga, intense hydrothermal activity was initiated by post-orogenic extension and uplift with 18O-poor meteoric water circulated along crustal structures. Compositions of Na+, K+, Mg2+, Cl–, CO32–, 34S-rich SO42–, 11B-rich borate, and other soluble salts minerals were leached from the evaporitic rocks of the Liaohe Group, which driving the ore-forming hydrothermal fluids toward slightly alkaline and weakly oxidized as system matures. As the alkaline fluids migrated along the structures and fractures in the BIFs and reacted with the wall rocks, SiO2 was mobilized from the low-grade iron ores and consequently formed chlorite, garnet, and tremolite in the wall rocks due to reactions with clay minerals. These Si-rich hydrothermal fluids was also related to vein type quartz and massive quartz-bearing rocks. Most Fe was retained in situ and resulted in the formation of magnetite-rich iron ores. The SO42– in the hydrothermal fluids was reduced to form pyrite while B in the hydrothermal fluids reacted with the wall rocks to form 11B-rich tourmaline.
Tissue damage caused by hyperthermia during photothermal therapy (PTT) has largely limited its clinical applications for implant infection. However, rescue of tissue regeneration by conjugating ...orthobiologics with PTT has been problematic as they can easily deactivate biologics while eradicating bacteria. Herein, we report an orthobiologics-free strategy to synergistically couple photocatalytic antibacterial with pro-osteogenic capacity via self-assembly of copper sulphide nanoparticle (CuS NP) and reduced graphene oxide (rGO) on implant surface. This strategy not only offers enhanced photothermal effects for bacterial eradiation via near-infrared light (NIR), but also promotes vascularized osseointegration via cooperation of copper ion with rGO. In vitro and in vivo data showed that coupling CuS and rGO synergistically increased antibacterial efficacy of implants by 40 times and successfully destroyed bacterial biofilm upon NIR. Moreover, CuS/rGO decorated surface substantially improved bone marrow stromal cell adhesion, proliferation, as well as subsequent differentiation toward osteoblast. We also revealed that enhanced peri-implant vascularization may be attributed to the sustained release of copper ion from CuS NPs, which further collaborated with rGO to promote vascularized osseointegration. Altogether, this novel orthobiologics-free approach offers a practical alternative to circumvent the intrinsic drawbacks of PTT and endows powerful antibacterial and pro-osteogenic capacities for implant associated infections.
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