Differential involvement of Wnt signaling in Bmp regulation of cancellous versus periosteal bone growth

Bone morphogenetic proteins （Bmp） are well-known to induce bone formation following chondrogenesis, but the direct role of Bmp signaling in the osteoblast lineage is not completely understood. We have recently shown that deletion of the receptor Bmprla in the osteoblast lineage with Dmpl-Cre reduces osteoblast activity in general but stimulates proliferation of preosteoblasts specifically in the cancellous bone region, resulting in diminished periosteal bone growth juxtaposed with excessive cancellous bone formation. Because expression of sclerostin （SOST）, a secreted Wnt antagonist, is notably reduced in the Bmprla- deficient osteocytes, we have genetically tested the hypothesis that increased Wnt signaling might mediate the increase in cancellous bone formation in response to Bmprla deletion. Forced expression of human SOST from a Dmpl promoter fragment partially rescues preosteoblast hyperproliferation and cancellous bone overgrowth in the Bmprla mutant mice, demonstrating functional interaction between Bmp and Wnt signaling in the cancellous bone compat^a-tent. To test whether increased Wnt signaling can compensate for the defect in periosteal growth caused by Bmprla deletion, we have generated compound mutants harboring a hyperactive mutation （A214V） in the Wnt receptor Lrp5. However, the mutant Lrp5 does not restore periosteal bone growth in the Bmprla-deficient mice. Thus, Bmp signaling restricts cancellous bone accrual partly through induction of SOST that limits preosteoblast proliferation, but promotes periosteal bone growth apparently independently of Wnt activation.

High Performance Bilinear Differential Preamplifier for BESⅢ Time-of-Flight System

A time-of-flight (TOF) detector has been used in the BESIII experiment to provide charged particle identification. In this paper, we present a novel high performance differential amplifier, which has been designed for amplifying the signals from the detectors. The preamplifier can amplify differential signals, which can help to eliminate the common mode pickup, and increase the signal-to-noise ratio (SNR). Bilinear gain is one of the features of this preamplifier, which greatly increases the dynamic range and avoids the dead time of the preamplifier. In order to describe the bilinear gain, a 4-parameter function is developed. And this 4-parameter function can also be used in the calibration of the time walk caused by the amplitude due to the bilinear gain. The preamplifier has a gain about 10V/V with a small signal and about 1.0V/V with a large signal. The rise time of the preamp is less than 2 ns.

Broad-Band All-Optical Wavelength Conversion of Differential Phase-Shift Keyed Signal Using an SOA-Based Nonlinear Polarization Switch

Broad-band all-optical wavelength conversion of differential phase-shift keyed （DPSK） signal is experimentally demonstrated. This scheme is composed of a one-bit delay interferometer demodulation stage followed by a semiconductor optical amplifier （SOA） based nonlinear polarization switch. A wavelength converter for the 10 G b/s DPSK signal is presented, which has a wide wavelength range of more than 30 nm. The converted signals experience small power penalties less than 1.4 dB compared with the original signal, at a bit error rate of 10-9. Additionally, the optical spectra, the measured waveforms and the open eye diagrams of the converted signals show a high quality wavelength conversion performance.

RANKL-RANK signaling regulates osteoblast differentiation and bone formation

In the recent two decades, it has been well elucidated that receptor activator of nuclear factor-κB ligand （RANKL; also known as TNFSF11） binding to its receptor RANK （also known as TNFRSF11A） drives osteoclast development as the crucial signaling pathway.;However, accumulating evidence also implies that

Rho/Rock signal transduction pathway is required for MSC tenogenic differentiation

Mesenchymal stem cell （MSC）-based treatments have shown promise for improving tendon healing and repair. MSCs have the potential to differentiate into multiple lineages in response to select chemical and physical stimuli, including into tenocytes. Cell elongation and cytoskeletal tension have been shown to be instrumental to the process of MSC differentiation. Previous studies have shown that inhibition of stress fiber formation leads MSCs to default toward an adipogenic lineage, which suggests that stress fibers are required for MSCs to sense the environmental factors that can induce differentiation into tenocytes. As the Rho/ROCK signal transduction pathway plays a critical role in both stress fiber formation and in cell sensation, we examined whether the activation of this pathway was required when inducing MSC tendon differentiation using rope-like silk scaffolds. To accomplish this, we employed a loss-of-function approach by knocking out ROCK, actin and myosin （two other components of the pathway） using the specific inhibitors Y-27632, Latrunculin A and blebbistatin, respectively. We demonstrated that independently disrupting the cytoskeleton and the Rho/ ROCK pathway abolished the expression of tendon differentiation markers and led to a loss of spindle morphology. Together, these studies suggest that the tension that is generated by MSC elongation is essential for MSC teno-differentiation and that the Rho/ROCK pathway is a critical mediator of tendon differentiation on rope-like silk scaffolds.

Identification of Steady State and Transient State

Identification of steady state and transient state plays an important role in modeling,control,optimiza-tion,and fault detection of industrial processes.Many existing methods for state identification are not satisfactory in practical applications due to problems of ideal hypothesis,too many parameters,and poor robustness.In this paper,a novel state identification approach is proposed.The problem of state identification is transformed into finding the noise band of differential signal.For practical application,automatic selection of noise band amplitude is proposed to make the method convenient to be used.Problems of gross errors,low signal-to-noise ratio and online identification are considered.And comparison with other two methods shows that the proposed method has better identification performance.Simulations and experiments also prove the effectiveness and practicability of the proposed method.

Implementation of low-swing differential interface circuits for high-speed on-chip asynchronous interconnection

A novel low-swing interface circuit for high-speed on-chip asynchronous interconnection is proposed in this paper. It takes a differential level-triggered latch to recover digital signal with ultra low-swing voltage less than 50 mV, and the driver part of the interface circuit is optimized for low power using the driver-array method, With a capacity to work up to 500 MHz, the proposed circuit, which is simulated and fabricated using SMIC 0.18-pm 1.8-V digital CMOS technology, consumes less power than previously reported designs.

A Novel System for Xylem Cell Differentiation in Arabidopsis thaliana

During vascular development, procambial and cambial cells give rise to xylem and phloem cells. Because the vascular tissue is deeply embedded, it has been difficult to analyze the processes of vascular development in detail. Here, we establish a novel in vitro experimental system in which vascular development is induced in Arabidopsis thaliana leaf-disk cultures using bikinin, an inhibitor of glycogen synthase kinase 3 proteins. Transcriptome analysis reveals that mesophyll cells in leaf disks synchronously turn into procambial cells and then differentiate into tracheary elements. Leaf-disk cultures from plants expressing the procambial cell markers TDRpro：GUS and TDRpro：YFP can be used for spatiotemporal visualization of procambial cell formation. Further analysis with the tdr mutant and TDIF （tracheary element differentiation inhibitory factor） indicates that the key signaling TDIF-TDR-GSK3s regulates xylem differentiation in leaf-disk cultures. This new culture system can be combined with analysis using the rich material resources for Arabidopsis including cell-marker lines and mutants, thus offering a powerful tool for analyzing xylem cell differentiation.

Electroacupuncture Attenuates Immune-Inflammatory Response in Hippocampus of Rats with Vascular Dementia by Inhibiting TLR4/MyD88 Signaling Pathway

Objective:To investigate whether electroacupuncture(EA)alleviates cognitive impairment by suppressing the toll-like receptor 4(TLR4)/myeloid differentiation factor 88(MyD88)signaling pathway,which triggers immune-inflammatory responses in the hippocampus of rats with vascular dementia(VaD).Methods:The experiments were conducted in 3 parts and in total the Sprague-Dawley rats were randomly divided into 8 groups by a random number table,including sham,four-vessel occlusion(4-VO),4-VO+EA,4-VO+non-EA,sham+EA,4-VO+lipopolysaccharide(LPS),4-VO+LPS+EA,and 4-VO+TAK-242 groups.The VaD model was established by the 4-VO method.Seven days later,rats were treated with EA at 5 acupoints of Baihui(DV 20),Danzhong(RN 17),Geshu(BL 17),Qihai(RN 6)and Sanyinjiao(SP 6),once per day for 3 consecutive weeks.Lymphocyte subsets,lymphocyte transformation rates,and inflammatory cytokines interleukin-6(IL-6)and tumor necrosis factorα(TNF-α)were measured to assess immune function and inflammation in VaD rats.Transmission electron microscopy was used to observe the ultrastructure of nerve cells in the hippocampus.The levels of TLR4,MyD88,IL-6,and TNF-αwere detected after EA treatment.TLR4/MyD88 signaling and cognitive function were also assessed after intracerebroventricular injection of TLR4 antagonist TAK-242 or TLR4 agonist LPS with or without EA.Results:Compared with the 4-VO group,EA notably improved immune function of rats in the 4-VO+EA group,inhibited the protein and mRNA expressions of TLR4 and MyD88 in the hippocampus of rats,reduced the expressions of serum IL-6 and TNF-α(all P<0.05 or P<0.01),and led to neuronal repair in the hippocampus.There were no significant differences between the 4-VO+LPS+EA and 4-VO+EA groups,nor between the 4-VO+TAK-242 and 4-VO+EA groups(P>0.05).Conclusions:EA attenuated cognitive impairment associated with immune inflammation by inhibition of the TLR4/MyD88 signaling pathway.Thus,EA may be a promising alternative therapy for the treatment of VaD.