Effect and mechanism of gomisin D on the isoproterenol induced myocardial injury in H9C2 cells and mice.

We established myocardial injury models in vivo and in vitro to investigate the cardioprotective effect of gomisin D obtained from Schisandra chinensis. Gomisin D significantly inhibited isoproterenol-induced apoptosis and hypertrophy in H9C2 cells. Gomisin D decreased serum BNP, ANP, CK-MB, cTn-T levels and histopathological alterations, and inhibited myocardial hypertrophy in mice. In mechanisms research, gomisin D reversed ISO-induced accumulation of intracellular ROS and Ca2+. Gomisin D further improved mitochondrial energy metabolism disorders by regulating the TCA cycle. These results demonstrated that gomisin D had a significant effect on isoproterenol-induced myocardial injury by inhibiting oxidative stress, calcium overload and improving mitochondrial energy metabolism.

Surpassing the limitation of a coherence length in lidar by digital coherence.

In this manuscript, we propose a digital coherent detection method to surpass the limitation of a coherent length on the detection range of a coherent lidar. This method rapidly reconstructs the laser phase noise utilizing the multi-channel delay self-homodyne and the generalized inverse of the system observation matrix. Subsequently, the reconstructed phase noise is utilized to expunge its perturbation onto the target information in the digital domain, thereby effectively surmounting the coherence length limitation. Through experimentation, the proposed method is verified to produce stable and high-quality interference even when the optical path difference between two beams exceeds 1000 times the coherence length. Additionally, the equivalent laser linewidth is compressed by 105 times.

Long distance high resolution FMCW laser ranging with phase noise compensation and 2D signal processing.

A long distance high resolution frequency-modulated continuous wave (FMCW) laser rangefinder with phase noise compensation and two-dimensional (2D) data processing skills is developed. Range-finding ladar consists of a continuously chirped laser source, an auxiliary reference interferometer, and a monostatic optical transceiver for target illumination and return photon collection. To extend the range unambiguity and lower the electronic processing bandwidth, a two-step laser frequency chirping scheme is adopted, where a long pulse width, small frequency bandwidth laser chirping signal are used in step 1 for coarse distance estimation, and a short pulse width and large frequency bandwidth laser chirping signal are applied afterwards for step 2 high resolution distance realization. An auxiliary reference interferometer is to record the phase noise originated from the laser source to compensate for phase errors induced in the target return photons. The 2D data processing skill helps to coherently sum up all the phase noise removed echo photons to achieve high resolution range peak extraction with high detection sensitivity. Experimental demonstration shows that the proposed FMCW ladar at 1550 nm wavelength with a laser chirping bandwidth of 10 GHz and electronic processing bandwidth of 200 MHz can measure a corner cube test target in an outdoor atmospheric environment, and the measurement results are 12013.905 m with a 2.4 cm range resolution under strong return photon levels and 12013.920 m with a 2.5 cm range resolution under weak return photon levels.

FMCW lidar multitarget detection based on skeleton tree waveform matching.

Frequency-modulated continuous-wave lidar realizes 4D (three-dimensional space and velocity) imaging of the scene by emitting positive and negative frequency sweep laser signals. The premise of it is to identify the frequency points corresponding to the same target in the positive and negative sweep echo signals. For dechirp receiving, there is usually one peak in the frequency spectrum of the positive and negative sweep signals, respectively. Therefore, it is easy to identify and match the peaks. But in a complex environment, the laser beam will irradiate multiple targets at the same time. In addition, beam scanning and target motion cause the echo spectrum to broaden. The above reasons make it extremely difficult to identify and match peaks in practice. To solve this problem, the waveform-matching algorithm based on the skeleton tree is first applied to multitarget echo pairing. The basic idea of the algorithm is to quantify the target echo hierarchically to generate a skeleton tree. The generation of nodes is based on the relative amplitude of waveform peaks and reflects the characteristics of wave crests nesting. Then the similarity of the signal is determined by comparing the distance between the two signal waveform feature trees. Finally, the waveforms are matched in terms of similarity. To further substantiate the role of the proposed algorithm, imaging experiments and related comparative data for different targets have been completed. The results show that the accuracy of matching processed by the algorithm exceeds 90%, which is improved by about 50% compared with not using the algorithm for the target whose overlapping part accounts for a large proportion of itself.

Feature extraction algorithm of precession target based on image length and Doppler broadening.

In space defense, utilizing the micromotion features to distinguish real targets from interfering targets and decoys is effective. Due to the imaging of the high-speed precession target by microwave radar consisting of isolated scattering centers, there are many difficulties in using inverse synthetic aperture radar (ISAR) images for feature extraction. On the other hand, the inverse synthetic aperture ladar (ISAL) image is relatively continuous because of the short wavelength of laser, and the image sequence contains information about the variation in image length and Doppler width caused by target precession, which can be used for inverse motion parameters. By establishing an observation model of the precession target and performing image processing on the obtained ISAL image at different times, the image length sequence and Doppler width sequence can be obtained. Using the ellipse fitting method to process the obtained sequence, the precession parameters of the target can be obtained. The algorithm does not require prior information such as the radius and speed of the target motion, effectively improving the practicability of the algorithm. Finally, the effectiveness of the algorithm is verified by experimental results, and the error is controlled within 2%.

Single-frequency LADAR super-resolution Doppler tomography for extended targets.

Doppler tomography is an important means to obtain two-dimensional (2-D) images of remote targets. It is especially suitable for imaging spinning targets such as space debris, warheads, and aircraft blades. However, related research is mostly focused on the microwave band rather than the laser. Higher resolution can be achieved by implementing Doppler tomography in the laser band compared to the existing Doppler tomography in the microwave. Moreover, existing imaging methods are mostly directed at point targets. When these methods deal with extended target echoes, the image quality is unsatisfactory. These problems severely limit the application of Doppler tomography. Here, a novel laser Doppler tomography method has been proposed. The method is based on a single-frequency laser radar (LADAR) that does not require any form of wideband modulation of the transmitted signal. The imaging process is based on the precise relationship between the scattering coefficient of the target and the statistical characteristics of the Doppler spectrum and finds the maximum a posteriori (MAP) estimate of the scattering coefficient distribution. The imaging resolution depends on the Doppler frequency resolution, which exceeds the diffraction limit and is independent of the imaging distance. A laser Doppler tomography experimental system was established. With this system, high-quality laser Doppler tomograms of extended targets were obtained for the first time. In the experiment, the targets have different rotational speeds from 100 to 1000 r/min. The images of these targets with a resolution of 0.4 mm are obtained at a distance of 5 m indoors. In these images, the target details such as textures on the surfaces can be rendered. The quality of these images is greatly improved compared to existing processing methods. The experimental results confirm the effectiveness of the proposed laser Doppler tomography method.

Feature extraction algorithm of a precession target based on a Doppler frequency profile of dual-aspect observation.

In ballistic missile defense, using precession parameters is an effective way to determine warheads from decoys. Due to the geometric theory of diffraction, the backscattered field from a smooth object for a microwave radar consists of contributions from only isolated scattering centers. Further, thanks to the short wavelength of the laser, the ladar could obtain complete Doppler information of illuminated parts of precessing targets. On the basis of modeling the observation geometry of a rotating target with precession, a novel method for extracting precession parameters using coherent ladar based on a Doppler frequency profile (DFP) of dual-view observation is first proposed, to the best of our knowledge. By analyzing the periodic changes of bandwidth of a cone-shaped precessing object, we indicate that the sequence of DFP bandwidth can be approximate to a sinusoid function, based on which the precession period can be obtained through sinusoidal fitting. The precession angle can be obtained by combining dual-aspect receiving observation. A laboratory experiment verified the effectiveness of the proposed algorithm, and the errors of extracted parameters are about 10%.

Inverse synthetic aperture ladar autofocus imaging algorithm for micro-vibrating satellites based on two prominent points.

As an important imaging method for long-range satellite targets, inverse synthetic aperture ladar (ISAL) has the characteristics of high-resolution imaging and competitive detectability. Since the working wavelength of the ISAL is comparable to the micro-vibrations generated by mechanical moving components of satellites, which will cause image defocusing, motion compensation is of great significance. In this paper, an autofocus algorithm is proposed for estimating and compensating the phase error relating to both translational and rotational micro-vibrations. Comparing with non-parametric algorithms like phase gradient autofocus and parametric algorithms like contrast-based autofocus and entropy-based autofocus, the proposed one, which is based on two prominent points, is especially effective for the rotational phase error oscillating numbers of cycles. Simulations and experiments are conducted to validate the feasibility of the proposed algorithm.

Three-dimensional inverse synthetic aperture lidar imaging for long-range spinning targets.

We present a three-dimensional (3D) imaging method for long-range spinning targets. This method acquires multi-angle two-dimensional (2D) images of spinning targets by the inverse synthetic aperture lidar (ISAL) imaging technique. The 3D distribution of the scattering coefficients of a target has a mapping relationship with the series of 2D images. This mapping is analyzed, and a 3D Hough transform is used to implement inverse mapping. The parameter space of the Hough transform is the estimation of the 3D distribution of the scattering coefficients. The 3D point spread function obtained by the method has narrow main lobe widths and sufficiently low side lobes to achieve high image quality, which is verified by computer simulations. In the simulations, the main lobe widths in the three dimensions are 0.29 cm, 0.29 cm, and 3.48 cm, respectively. In outdoor experiments, 3D images of targets at 1 km away from the lidar were obtained. The images clearly show the 3D shape of targets.

Inverse synthetic aperture LADAR demonstration: system structure, imaging processing, and experiment result.

A long-distance inverse synthetic aperture LADAR (ISAL) imaging experiment outdoors over 1 km for cooperative targets is demonstrated, which gets a two-dimensional high-resolution image with resolution exceeding 2.5 cm. The system utilizes an electro-optic in-phase and quadrature modulator to output a linear frequency-modulated continuous waveform (LFMCW) with a bandwidth of 6 GHz and pulse repetition frequency (PRF) of 16.7 KHz. For the problem of the coherence of the laser, the effects of the coherent processing interval (CPI) and time delay of the local oscillator (LO) on the coherence are discussed. The fiber delay line is set and the CPI is reduced to lower the requirement of the frequency stability of the laser source. The images are formed by two-dimensional Fourier transform and joint time-frequency transform methods, respectively. In this paper, we present the system structure, imaging processing, and the experiment result in detail. The experiment result validates the performance of our system for ISAL imaging.

The gender gap among school children in poor rural areas of western China: evidence from a multi-province dataset.

BACKGROUND: The gender gap remains a major impediment in the path towards equality and it is especially wide in low-income countries. Up to the early 2000s, many studies documented extensive inequalities in China: girls had poorer health, less nutrition and less education than their male counterparts. The goal of this study is to examine whether the gender gap persists, given that China is now making the transition into the ranks of upper-middle income countries. We consider educational outcomes, mental and physical health status, as well as non-cognitive outcomes. METHODS: We draw on a dataset containing 69,565 observations constructed by combining data from 7 different school-level surveys spanning 5 provinces. The surveys were all conducted by the authors between 2008 and 2013 using uniform survey instruments and data collection protocols in randomly selected schools across western provinces in rural China. The sample children range in age from 9 to 14 years (with 79 % of the sample being aged 10 to 12). Our analysis compares rural girls with rural boys in terms of 13 different indicators. RESULTS: With the exception of anemia rates, the health outcomes of girls are equal to those of boys. Girls and boys are statistically identical in terms of weight-for-age, height-for-age, and prevalence of intestinal worm infections. Girls performed better than boys on five of six cognitive and educational performance indicators. Girls performed worse than boys on all mental health indicators. All estimates are robust to the inclusion of different age ranges, controlling for the level of household assets, ethnic minority status, as well as the addition of provincial dummies. CONCLUSIONS: Our findings suggest that with the exception of non-cognitive outcomes, anemia and standardized math test scores, the gender gap in our study areas in China appears to be diminishing.

Synthesis and potent inhibitory activities of carboxybenzyl-substituted 8-(3-(R)-aminopiperidin-1-yl)-7-(2-chloro/cyanobenzyl)-3-methyl-3,7-dihydro-purine-2,6-diones as dipeptidyl peptidase IV (DPP-IV) inhibitors.

Fourteen 3-methyl-3,7-dihydro-purine-2,6-dione derivatives 1-14 bearing carboxybenzyl and 2-chloro/cyanobenzyl groups at the N-1 and N-7 positions, respectively, were synthesized as dipeptidyl peptidase IV (DPP-IV) inhibitors. These compounds were characterized on the basis of NMR ((1)H and (13)C) and ESI MS data. In vitro bioassay indicates that most of these compounds showed moderate to good inhibitory activities against DPP-IV. Among them, compound 13 (IC50=36 nM) exhibited comparable activity with a positive control, Sitagliptin (IC50=16 nM). In addition, the structure-activity relationship of these compounds is also briefly discussed.

Multiple biosynthetic trafficking routes for apically secreted proteins in MDCK cells.

Many newly synthesized membrane proteins traverse endocytic intermediates en route to the surface in polarized epithelial cells; however, the biosynthetic itinerary of secreted proteins has not been elucidated. We monitored the trafficking route of two secreted proteins with different apical sorting signals: the N-glycan-dependent cargo glycosylated growth hormone (gGH) and Ensol, a soluble version of endolyn whose apical sorting is independent of N-glycans. Both proteins were observed to colocalize in part with apical recycling endosome (ARE) markers. Cargo that lacks an apical targeting signal and is secreted in a nonpolarized manner did not localize to the ARE. Expression of a dominant-negative mutant of myosin Vb, which disrupts ARE export of glycan-dependent membrane proteins, selectively inhibited apical release of gGH but not Ensol. Fluorescence recovery after photobleaching (FRAP) measurements revealed that gGH in the ARE was less mobile than Ensol, consistent with tethering to a sorting receptor. However, knockdown of galectin-3 or galectin-4, lectins implicated in apical sorting, had no effect on the rate or polarity of gGH secretion. Together, our results suggest that apically secreted cargoes selectively access the ARE and are exported via differentially regulated pathways.

OCRL1 modulates cilia length in renal epithelial cells.

Lowe syndrome is an X-linked disorder characterized by cataracts at birth, mental retardation and progressive renal malfunction that results from loss of function of the OCRL1 (oculocerebrorenal syndrome of Lowe) protein. OCRL1 is a lipid phosphatase that converts phosphatidylinositol 4,5-bisphosphate to phosphatidylinositol 4-phosphate. The renal pathogenesis of Lowe syndrome patients has been suggested to result from alterations in membrane trafficking, but this cannot fully explain the disease progression. We found that knockdown of OCRL1 in zebrafish caused developmental defects consistent with disruption of ciliary function, including body axis curvature, pericardial edema, hydrocephaly and impaired renal clearance. In addition, cilia in the proximal tubule of the zebrafish pronephric kidney were longer in ocrl morphant embryos. We also found that knockdown of OCRL1 in polarized renal epithelial cells caused elongation of the primary cilium and disrupted formation of cysts in three-dimensional cultures. Calcium release in response to ATP was blunted in OCRL1 knockdown cells, suggesting changes in signaling that could lead to altered cell function. Our results suggest a new role for OCRL1 in renal epithelial cell function that could contribute to the pathogenesis of Lowe syndrome.

Apical targeting and endocytosis of the sialomucin endolyn are essential for establishment of zebrafish pronephric kidney function.

Kidney function requires the appropriate distribution of membrane proteins between the apical and basolateral surfaces along the kidney tubule. Further, the absolute amount of a protein at the cell surface versus intracellular compartments must be attuned to specific physiological needs. Endolyn (CD164) is a transmembrane protein that is expressed at the brush border and in apical endosomes of the proximal convoluted tubule and in lysosomes of more distal segments of the kidney. Endolyn has been shown to regulate CXCR4 signaling in hematopoietic precursor cells and myoblasts; however, little is known about endolyn function in the adult or developing kidney. Here we identify endolyn as a gene important for zebrafish pronephric kidney function. Zebrafish endolyn lacks the N-terminal mucin-like domain of the mammalian protein, but is otherwise highly conserved. Using in situ hybridization we show that endolyn is expressed early during development in zebrafish brain, eye, gut and pronephric kidney. Embryos injected with a translation-inhibiting morpholino oligonucleotide targeted against endolyn developed pericardial edema, hydrocephaly and body curvature. The pronephric kidney appeared normal morphologically, but clearance of fluorescent dextran injected into the common cardinal vein was delayed, consistent with a defect in the regulation of water balance in morphant embryos. Heterologous expression of rat endolyn rescued the morphant phenotypes. Interestingly, rescue experiments using mutant rat endolyn constructs revealed that both apical sorting and endocytic/lysosomal targeting motifs are required for normal pronephric kidney function. This suggests that both polarized targeting and postendocytic trafficking of endolyn are essential for the protein's proper function in mammalian kidney.

Core-glycosylated mucin-like repeats from MUC1 are an apical targeting signal.

MUC1 is efficiently delivered to the apical surface of polarized Madin-Darby canine kidney (MDCK) cells by transit through apical recycling endosomes, a route associated with delivery of apical proteins with glycan-dependent targeting signals. However, a role for glycans in MUC1 sorting has not been established. A key feature of MUC1 is a heavily O-glycosylated mucin-like domain with a variable number of nearly perfect tandem repeats and adjacent imperfect repeats. Metabolic labeling, cell surface biotinylation, immobilized lectins, and confocal immunofluorescence microscopy were used to characterize the polarized delivery of MUC1 mutants and chimeras in MDCK cells to identify the apical targeting signal. Both the interleukin-2 receptor α subunit (Tac) and a chimera where the Tac ectodomain replaced that of MUC1 were delivered primarily to the basolateral surface. Attachment of the MUC1 mucin-like domain to the N terminus of Tac enhanced apical but not basolateral delivery when compared with Tac. Conversely, deletions within the mucin-like domain in MUC1 reduced apical but not basolateral delivery when compared with MUC1. In pull-down assays with lectins, we found a notable difference in the presence of core 1 O-glycans, but not poly-N-acetyllactosamine, in apically targeted MUC1 and chimeras when compared with Tac. Consistent with these data, we found no effect on MUC1 targeting when galectin-3, with preference for poly-N-acetyllactosamine, was depleted from polarized MDCK cells. However, we did block the apical targeting activity of the mucin-like repeats when we overexpressed CMP-Neu5Ac:GalNAc-Rα2,6-sialyltransferase-1 to block core O-glycan synthesis. The cumulative data indicate that the core-glycosylated mucin-like repeats of MUC1 constitute an apical targeting signal.

Circadian regulation of breath alcohol concentration.

STUDY OBJECTIVES: The role of the circadian clock in regulating blood/breath alcohol levels after consuming alcohol is uncertain. Our goal was to evaluate the degree to which the circadian system regulates breath alcohol concentration (BrAC) pharmacokinetic parameters. METHODS: Twenty healthy adults aged 21-30 years took part in a 4-day laboratory study. A 40-h constant routine procedure was used to assess circadian rhythms. Every 4 h, participants were given a fixed oral dose of alcohol with breathalyzer measurements taken every 5 min to construct BrAC curves. Sinusoidal models were used to test for circadian variation of the peak BrAC, the time to reach peak BrAC, the absorption rate, the elimination rate, and the time for BrAC to return to zero after alcohol was ingested. RESULTS: A significant circadian rhythm was detected for group-averaged peak BrAC values and the time for BrAC to return to zero, but not other BrAC variables. Peak BrAC values were lowest in the evening near the peak of the core body temperature rhythm and nadir of the salivary cortisol rhythm. Peak BrAC values increased during the night and reached their highest levels in the morning and afternoon. The time needed for BrAC to return to zero was also longest in the late morning and afternoon. CONCLUSION: The circadian system modulates some BrAC pharmacokinetic parameters. In normally entrained individuals, taking the same oral dose of alcohol at different times of day can result in different BrAC responses. These findings have potential implications for alcohol-related accidents and alcohol toxicity.

Time Efficiency of Immediate Loading of Full-arch Implant Reconstructions Using Prefabricated Prostheses Located by an Anchor Pin: a Pilot Study.

OBJECTIVE: To investigate the time efficiency of prefabricated prostheses located by an anchor pin stereolithographic attachment system for immediate loading implant reconstruction of completely edentulous jaws and compare it with the conventional protocol. METHODS: Edentulous patients were recruited and randomly assigned into two groups: the full digital workflow group (digital group) and the conventional workflow group (conventional group). In the digital group, a provisional prosthesis was fabricated before surgery using a fully digital workflow and delivered immediately after implant placement. The positioning of the provisional prosthesis was guided precisely by the anchor pin attachment system. In the conventional group, the provisional prosthesis was fabricated after implant placement using a conventional procedure. Clinical and laboratory time efficiency were recorded, and clinician and patient satisfaction were evaluated. RESULTS: Six patients were enrolled in this pilot study and 57 implants were placed following the guided surgery protocol. Of these, 54 were immediately loaded. The total clinical chair time in the digital workflow group was significantly less than that in the conventional workflow group (digital 60.0 ± 13.2 minutes; conventional 106.7 ± 24.7 minutes) (P = 0.045). The total post-surgery procedure took significantly less time in the digital group than the conventional group (digital 202.5 ± 22.5 minutes; conventional 403.7 ± 55.4 minutes) (P = 0.004). The patients' and clinicians' satisfaction with the provisional prostheses was similar in both groups. CONCLUSION: Time efficiency in immediate loading of implant-supported full-arch fixed restorations was improved with prefabricated prostheses located by the anchor-pin-attachment system. Less postoperative chair time was required in the digital group than in the conventional group.

Nucleofection disrupts tight junction fence function to alter membrane polarity of renal epithelial cells.

Here, we compared the effects of nucleofection and lipid-based approaches to introduce siRNA duplexes on the subsequent development of membrane polarity in kidney cells. Nucleofection of Madin-Darby canine kidney (MDCK) cells, even with control siRNA duplexes, disrupted the initial surface polarity as well as the steady-state distribution of membrane proteins. Transfection using lipofectamine yielded slightly less efficient knockdown but did not disrupt membrane polarity. Polarized secretion was unaffected by nucleofection, suggesting a selective defect in the development of membrane polarity. Cilia frequency and length were not altered by nucleofection. However, the basolateral appearance of a fluorescent lipid tracer added to the apical surface of nucleofected cells was dramatically enhanced relative to untransfected controls or lipofectamine-treated cells. In contrast, [(3)H]inulin diffusion and transepithelial electrical resistance were not altered in nucleofected cells compared with untransfected ones. We conclude that nucleofection selectively hinders development of the tight junction fence function in MDCK cells.

Accuracy of Intraoral Scanning of Edentulous Jaws with and without Resin Markers.

Objective: To evaluate the accuracy of digital models obtained from intraoral scanning of edentulous maxilla and mandible models with and without resin markers. Methods: A pair of standard edentulous models were scanned using a laboratory scanner and saved as reference models. The edentulous models were fixed onto a phantom head and scanned with an intraoral scanner (IOS) five times each. Six resin markers were attached on the maxilla model and two on the mandible model, and another five intraoral scans were taken of each model. The scanning time and number of images were recorded. The digital models obtained using the IOS were superimposed on the reference models using image processing software. The trueness and precision of the models made using the IOS were evaluated, and the scanning time and number of images were also compared. Results: The average trueness and precision of the IOS in the maxilla model with resin markers were 135.50 ± 36.28 µm and 254.55 ± 40.62 µm, respectively, while those in the mandible were 161.40 ± 55.45 µm and 368.75 ± 91.03 µm, respectively. Placing resin markers on the edentulous maxilla and mandible did not improve the trueness of the IOS, but placing resin markers on the edentulous maxilla improved the precision and scanning efficiency. However, placing resin markers on the buccal shelf of the edentulous mandible decreased the precision and increased the scanning time. Conclusion: Resin markers placed on the hard palate of edentulous maxillae could improve the precision of the IOS and improve scanning efficiency. However, they did not affect the trueness of the IOS for edentulous maxillae or mandibles.