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Bladder cancer (BLCA) is one of the most malignant cancers worldwide, and its prognosis varies. 1214 BLCA samples in five different datasets and 2 platforms were enrolled in this study. By utilizing the gene expression in The Cancer Genome Atlas (TCGA) dataset, and another two datasets, in GSE13507 and GSE31684, we constructed a risk score staging system with Cox multivariate regression to evaluate predict the outcome of BLCA patients. Three genes consist of RCOR1, ST3GAL5, and COL10A1 were used to predict the survival of BLCA patients. The patients with low risk score have a better survival rate than those with high risk score, significantly. The survival profiles of another two datasets (GSE13507 and GSE31684), which were used for candidate gene selection, were similar as the training dataset (TCGA). Furthermore, survival prediction effect of risk score staging system in another 2 independent datasets, GSE40875 and E-TABM-4321, were also validated. Compared with other clinical observations, and the risk score performs better in evaluating the survival of BLCA patients. Moreover, the correlation between radiation were also evaluated, and we found that patients have a poor survival in high risk group, regardless of radiation. Gene Set Enrichment Analysis was also implemented to find the difference between high-risk and low-risk groups on biological pathways, and focal adhesion and JAK signaling pathway were significantly enriched. In summary, we developed a risk staging model for BLCA patients with three gene expression. The model is independent from and performs better than other clinical information.

Hutchinson–Gilford progeria syndrome (HGPS) is caused by the accumulation of mutant prelamin A (progerin) in the nuclear lamina, resulting in increased nuclear stiffness and abnormal nuclear architecture. Nuclear mechanics are tightly coupled to cytoskeletal mechanics via lamin A/C. However, the role of cytoskeletal/nuclear mechanical properties in mediating cellular senescence and the relationship between cytoskeletal stiffness, nuclear abnormalities, and senescent phenotypes remain largely unknown. Here, using muscle‐derived mesenchymal stromal/stem cells (MSCs) from the Zmpste24 −/− (Z24 −/−) mouse (a model for HGPS) and human HGPS fibroblasts, we investigated the mechanical mechanism of progerin‐induced cellular senescence, involving the role and interaction of mechanical sensors RhoA and Sun1/2 in regulating F‐actin cytoskeleton stiffness, nuclear blebbing, micronuclei formation, and the innate immune response. We observed that increased cytoskeletal stiffness and RhoA activation in progeria cells were directly coupled with increased nuclear blebbing, Sun2 expression, and micronuclei‐induced cGAS‐Sting activation, part of the innate immune response. Expression of constitutively active RhoA promoted, while the inhibition of RhoA/ROCK reduced cytoskeletal stiffness, Sun2 expression, the innate immune response, and cellular senescence. Silencing of Sun2 expression by siRNA also repressed RhoA activation, cytoskeletal stiffness and cellular senescence. Treatment of Zmpste24− / − mice with a RhoA inhibitor repressed cellular senescence and improved muscle regeneration. These results reveal novel mechanical roles and correlation of cytoskeletal/nuclear stiffness, RhoA, Sun2, and the innate immune response in promoting aging and cellular senescence in HGPS progeria., There is increased RhoA activation and cytoskeleton stiffness in progeria cells, which mediates increased nuclear blebbing, micronuclei formation, innate immune response, and cellular senescence. RhoA activation is coupled with elevated Sun2 expression, but not Sun1, especially in nucleus with blebbing and micronuclei. Repression of RhoA and Sun2 activation was able to reduce cytoskeleton stiffness, nuclear blebbing, and micronuclei formation and delay the progression of cellular senescence.

In view of the problems of exposure bias and insufficient annotation data in the existing Chinese short text summary algorithms, a new pre-training short text summary algorithm named ERNIE-GEN-CTS based on ERNIE-GEN is proposed. This paper uses pre-training language model to realize the double attention of word level and word level for short text, and fills the sub block with semantic information to optimize the exposure bias problem. After the pre-training model of large-scale Chinese corpus, the results are improved in LCSTS data set after the task tuning of the downstream summary, and the validity and stability of the model are verified.

Mice expressing reduced levels of ERCC1-XPF (Ercc1-/Δ mice) demonstrate premature onset of age-related changes due to decreased repair of DNA damage. Muscle-derived stem/progenitor cells (MDSPCs) isolated from Ercc1-/Δ mice have an impaired capacity for cell differentiation. The mammalian target of rapamycin (mTOR) is a critical regulator of cell growth in response to nutrient, hormone, and oxygen levels. Inhibition of the mTOR pathway extends the lifespan of several species. Here, we examined the role of mTOR in regulating the MDSPC dysfunction that occurs with accelerated aging. We show that mTOR signaling pathways are activated in Ercc1-/Δ MDSPCs compared with wild-type (WT) MDSPCs. Additionally, inhibiting mTOR with rapamycin promoted autophagy and improved the myogenic differentiation capacity of the Ercc1-/Δ MDSPCs. The percent of apoptotic and senescent cells in Ercc1-/Δ MDSPC cultures was decreased upon mTOR inhibition. These results establish that mTOR signaling contributes to stem cell dysfunction and cell fate decisions in response to endogenous DNA damage. Therefore, mTOR represents a potential therapeutic target for improving defective, aged stem cells. © 2016 The Authors. Journal of Orthopaedic Research Published by Wiley Periodicals, Inc. on behalf of Orthopaedic Research Society. J Orthop Res 35:1375-1382, 2017.

Progressive muscle weakness and degeneration due to the lack of dystrophin eventually leads to the loss of independent ambulation by the middle of the patient's second decade, and a fatal outcome due to cardiac or respiratory failure by the third decade. More specifically, loss of sarcolemmal dystrophin and the dystrophin-associated glycoprotein (DAG) complex promotes muscle fiber damage during muscle contraction. This process results in an efflux of creatine kinase (CK), an influx of calcium ions, and the recruitment of T cells, macrophages, and mast cells to the damaged muscle, causing progressive myofiber necrosis. For the last 20 years, the major goal in the development of therapeutic approaches to alleviate muscle weakness in DMD has been centered on the restoration of dystrophin or proteins that are analogous to dystrophin, such as utrophin, through a variety of modalities including cell therapy, gene therapy, gene correction, and the highly promising techniques utilizing CRISPR/Cas9 technology. Despite the development of new therapeutic options, there still exist numerous challenges that we must face with regard to these new strategies and, consequently, we still do not have any feasible options available to ultimately slow the progression of this devastating disease. The purpose of this article is to highlight the current knowledge and advancements in the evolving paradigms in clinical pharmacology and therapeutics for this devastating musculoskeletal disease.

For improving the convergence accuracy and diversity of multi-objective optimization algorithm a multi-objective quantum-behaved particle swarm optimization algorithm with double-potential well and share-learning is proposed, which overcomes the deficiency of particles readily gathering in identical solutions. The two local attractors, inside and outside, are introduced to construct the particle locations updating model, using the quantum tunneling and transition effects in double-potential well model. In this way, the particle moves to the solution sparseness region in later evolution stage, so as to avoid gathering in the single local attractor and escape from local optimum. Therefore the optimization accuracy of the algorithm is improved. The share-learning strategy is adopted to extend the search range of particles and increase the diversity of solutions. The problem of easily converging to boundary solutions in quantum-behaved particle swarm optimization algorithm could be avoided. Simulation results show that the proposed algorithm makes excellent performance in optimization accuracy, convergence, diversity, and distribution, compared with three existing algorithms. Moreover, the proposed algorithm can hold on better convergence and distribution performance when handling high-dimensional multi-objective problems.

With the rapid deployment of large oil tank, a quick and efficient fire extinguishing foam generator becomes particularly critical to relieve the safety concerns. In this work, a cryogenic fluid/bulk fluid mixing apparatus, composed of a horizontal channel and a conical spoiler in it, is developed to generate stable and homogeneous foam flow. The flow and temperature characteristics of the mixing flow field, including flow pattern, contour of velocity and phase fraction, temperature and pressure profiles, are studied by a visualization experiment and numerical simulation. From the results, a typical flow pattern of liquid nitrogen jetting into bulk fluid (water or foam liquid) in the mixing channel is proposed. The rapid phase transition (RPT) of nitrogen liquid in bulk fluid is found to effectively enhance the mass and heat transfer between phases. Besides, the introduction of conical spoiler facilitates the flow mixing effectively. The nitrogen liquid jet is broken into small liquid blocks and vaporizes rapidly in the conical spoiler zone. A backflow zone appears at the downstream of the spoiler and further promotes the homogeneous foam flow. Moreover, compared to the liquid nitrogen/water mixing flow, the direct mixing of liquid nitrogen/foam liquid could accomplish higher foaming ability, and more homogenous and stable foam flow due to its lower surface tension, higher dispersivity, faster interphase heat and mass transfer. The study of characteristics of the mixing flow in this work could provide an important guidance for the design and optimization of foam generators in the compressed air foam systems (CAFSs).

Aiming at low precision of remote sensing image scene classification, a classification method DCNN_FF based on deep convolutional neural network (DCNN) feature fusion (FF) is proposed. This method utilizes the existing pre-trained network models CaffeNet and GoogLeNet, and extracts the features of the classified remote sensing images by fine tuning on the target dataset. After dimension reduction by principle component analysis (PCA), the features extracted from the two network models are combined. Finally, the support vector machine (SVM) is used for classification of the combined features. The experimental results on the commonly used and latest datasets show that, this method can utilize the existing network models and combine with the structural advantages of different models, and its average classification accuracy is higher than that of single network model by more than 1.68%. Thus it improves the accuracy of remote sensing image scene classification.

Aiming at the problem of large computing and time-consuming in two-dimensional maximum entropy based image segmentation method, this paper proposes a two-dimensional maximum entropy segmentation algorithm based on chicken swarm optimization. Chicken swarm optimization algorithm has certain advantage in convergence speed and convergence accuracy. Using these advantages, the objective function of two-dimensional maximum entropy is considered as the fitness function of chicken swarm optimization algorithm. And this method located the best threshold gradually and quickly by virtue of the role division of chickens and teamwork of roosters, hens and chicks. Experimental results show that the method is superior to some segmentation methods based on particle swarm optimization algorithm and artificial fish swarm algorithm in convergence and segmentation effects.

Nuclear factor κB (NF-κB) is a transcription factor important for regulating innate and adaptive immunity, cellular proliferation, apoptosis, and senescence. Dysregulation of NF-κB and its upstream regulator IκB kinase (IKK) contributes to the pathogenesis of multiple inflammatory and degenerative diseases as well as cancer. An 11–amino acid peptide containing the NF-κB essential modulator (NEMO)-binding domain (NBD) derived from the C-terminus of β subunit of IKK, functions as a highly selective inhibitor of the IKK complex by disrupting the association of IKKβ and the IKKγ subunit NEMO. A structure-based pharmacophore model was developed to identify NBD mimetics by in silico screening. Two optimized lead NBD mimetics, SR12343 and SR12460, inhibited tumor necrosis factor α (TNF-α)- and lipopolysaccharide (LPS)-induced NF-κB activation by blocking the interaction between IKKβ and NEMO and suppressed LPS-induced acute pulmonary inflammation in mice. Chronic treatment of a mouse model of Duchenne muscular dystrophy (DMD) with SR12343 and SR12460 attenuated inflammatory infiltration, necrosis and muscle degeneration, demonstrating that these small-molecule NBD mimetics are potential therapeutics for inflammatory and degenerative diseases., Author summary Aberrant up-regulation of the transcription factor nuclear factor κB (NF-κB) and the IκB kinase (IKK) that regulates NF-κB is associated with a variety of inflammatory and degenerative diseases in humans, including aging. Thus, development of effective and specific drugs able to decrease IKK/NF-κB activity has significant therapeutic potential. In this study, a structure-derived computational approach was used to screen for small-molecule inhibitors of the protein–protein interaction between the IKKß and IKKγ subunits of the IKK complex. We identified and developed a novel class of small molecules that selectively inhibit IKK/NF-κB activation by dissociating the IKK complex without affecting c-Jun N-terminal kinase (JNK)/p38-mitogen-activated protein kinase (MAPK) signaling. These novel molecules reduce lipopolysaccharide (LPS)-induced acute inflammation in mice and improve muscle pathology in the mdx mouse model of Duchenne muscular dystrophy (DMD), suggesting that they would have potential clinical utility.

S94 objective recognition not only classifies what category it is, but also detects sub-categories information to confirm the objective is what we want to find. Due to the problem that the number of labeled specific objective images is insufficient, and the subtle different between the specific objective and other objectives in the same category, we proposed an efficient method based on convolutional neural network (CNN) transfer learning. We adopted VGG16 network structure to learn low level visual feature, and the fully-connected layers were redesigned. The method retrained the last fully-connected layer and soft-max classifier, and fine-tuned the model with backpropagation algorithm. The experimental results show that the method makes it possible to use CNN fine-tuning for specific objective recognition with only small scale images, and effectively improves the accuracy of image classification.

A 1064 nm, 1 mJ pulsed fiber MOPA module, housed in 16”x14”x2.5” package for application in a lunar and planetary in-situ surface dating instrument is demonstrated. The module is based on a three-stage MOPA with a 60 μm core tapered fiber terminal amplifier. The master oscillator and first two preamplifier stages, which generate 20 μJ pulses, are all contained on a 13”x11”x1” board. Several improvements to the electronic signal control were instrumental to the laser development, including bipolar drive of the phase modulator for SBS suppression, shaping of the seed pulse to compensate pulse steepening, and pulsed operation of the power amplifier pump to reduce spontaneous emission at low pulse repetition frequency. The packaged laser runs at a repetition rate of 10 kHz and generates 10 ns pulses at 1 mJ with a 40 GHz linewidth, an M 2 ~ 1.2 beam quality, and an 18 dB polarization extinction ratio. The modular design enables seven independent lasers to be stacked in a 20”x18”x16.25” enclosure, supporting a path towards a fiber laser based LARIMS for advanced materials characterization and chronological dating in harsh and remote environments.

Although it has been speculated that stem cell depletion plays a role in the rapid progression of the muscle histopathology associated with Duchenne Muscular Dystrophy (DMD), the molecular and cellular mechanisms responsible for stem cell depletion remain poorly understood. The rapid depletion of muscle stem cells has not been observed in the dystrophin-deficient model of DMD (mdx mouse), which may explain the relatively mild dystrophic phenotype observed in this animal model. In contrast, we have observed a rapid occurrence of stem cell depletion in the dystrophin/utrophin double knockout (dKO) mouse model, which exhibits histopathological features that more closely recapitulate the phenotype observed in DMD patients compared with the mdx mouse. Notch signaling has been found to be a key regulator of stem cell self-renewal and myogenesis in normal skeletal muscle; however, little is known about the role that Notch plays in the development of the dystrophic histopathology associated with DMD. Our results revealed an over-activation of Notch in the skeletal muscles of dKO mice, which correlated with sustained inflammation, impaired muscle regeneration and the rapid depletion and senescence of the muscle progenitor cells (MPCs, i.e. Pax7+ cells). Consequently, the repression of Notch in the skeletal muscle of dKO mice delayed/reduced the depletion and senescence of MPCs, and restored the myogenesis capacity while reducing inflammation and fibrosis. We suggest that the down-regulation of Notch could represent a viable approach to reduce the dystrophic histopathologies associated with DMD.

Due to the limited space of the carrier, the multi-antenna system on the carrier is prone to electromagnetic interference. Most of the researchers used genetic algorithms to optimize the antenna layout. On this basis, this paper proposes a method of interactive simulation of MATLAB and electromagnetic simulation software CST. Firstly, the position information of the antenna and the carrier platform is initialized in MATLAB, and then the program of the genetic algorithm is run, and the layout scheme of each generation is automatically transmitted to the CST through the ActiveX. The CST solves the antenna coupling degree and automatically returns it to MATLAB as the fitness value of the scheme. After dozens of generations of genetic algorithms, a better layout scheme can be found. Compared with the previous optimization methods, the method of this paper does not need to build complex electromagnetic numerical calculation model, and it has strong operability and high degree of visualization. Therefore, it has certain reference for the layout optimization of multi-antenna systems of other carriers.

Aldehyde dehydrogenase (ALDH) is a cancer stem cell marker. Retinoic acid has antitumor properties, including the induction of apoptosis and inhibition of proliferation. Retinal, the precursor of retinoic acid, can be oxidized to retinoic acid by dehydrogenases, including ALDH. We hypothesized that retinal could potentially be transformed to retinoic acid with higher efficiency by cancer stem cells, due to the higher ALDH activity. We previously observed that ALDH activity is greater in highly metastatic K7M2 osteosarcoma (OS) cells than in nonmetastatic K12 OS cells. We also demonstrated that ALDH activity correlates with clinical metastases in bone sarcoma patients, suggesting that ALDH may be a therapeutic target specific to cells with high metastatic potential. Our current results demonstrated that retinal preferentially affected the phenotypes of ALDH-high K7M2 cells in contrast to ALDH-low K12 cells, which could be mediated by the more efficient transformation of retinal to retinoic acid by ALDH in K7M2 cells. Retinal treatment of highly metastatic K7M2 cells decreased their proliferation, invasion capacity, and resistance to oxidative stress. Retinal altered the expression of metastasis-related genes. These observations indicate that retinal may be used to specifically target metastatic cancer stem cells in OS.

In this paper, according to the characteristics of meteor burst communication network, a meteor burst network is designed based on OPNET simulation environment. Then the simulation results of the data amount of the corresponding nodes and the total amount of communication are obtained. Compared with the data of point-to-point node communication, the simulation results show that the simulation network can meet the characteristics of meteoric meteorological communication, and the design of the networking method improves the meteoric traces communication efficiency, which provides a reference for meteoric burst network construction.

Glucocorticoid treatment represents a standard palliative treatment for Duchenne muscular dystrophy (DMD) patients, but various adverse effects have limited this treatment. In an effort to understand the mechanism(s) by which glucocorticoids impart their effects on the dystrophic muscle, and potentially reduce the adverse effects, we have studied the effect of prednisolone treatment in dystrophin/utrophin double knockout (dKO) mice, which exhibit a severe dystrophic phenotype due to rapid muscle stem cell depletion. Our results indicate that muscle stem cell depletion in dKO muscle is related to upregulation of mTOR, and that prednisolone treatment reduces the expression of mTOR and other pro-inflammatory mediators, consequently slowing down muscle stem cell depletion. However, prednisolone treatment was unable to improve the myogenesis of stem cells and reduce fibrosis in dKO muscle. We then studied whether glucocorticoid treatment can be improved by co-administration of an inhibitor of RhoA/ROCK signaling, which can be activated by glucocorticoids and was found in our previous work to be over-activated in dystrophic muscle. Our results indicate that the combination of RhoA/ROCK inhibition and glucocorticoid treatment in dystrophic muscle have a synergistic effect in alleviating the dystrophic phenotype. Taken together, our study not only shed light on the mechanism by which glucocorticoid imparts its beneficial effect on dystrophic muscle, but also revealed the synergistic effect of RhoA/ROCK inhibition and glucocorticoid treatment, which could lead to the development of more efficient therapeutic approaches for treating DMD patients.

Duchenne muscular dystrophy (DMD) patients lack dystrophin from birth; however, muscle weakness becomes apparent only at 3–5 years of age, which happens to coincide with the depletion of the muscle progenitor cell (MPC) pools. Indeed, MPCs isolated from older DMD patients demonstrate impairments in myogenic potential. To determine whether the progression of muscular dystrophy is a consequence of the decline in functional MPCs, we investigated two animal models of DMD: (i) dystrophin-deficient mdx mice, the most commonly utilized model of DMD, which has a relatively mild dystrophic phenotype and (ii) dystrophin/utrophin double knock-out (dKO) mice, which display a similar histopathologic phenotype to DMD patients. In contrast to age-matched mdx mice, we observed that both the number and regeneration potential of dKO MPCs rapidly declines during disease progression. This occurred in MPCs at both early and late stages of myogenic commitment. In fact, early MPCs isolated from 6-week-old dKO mice have reductions in proliferation, resistance to oxidative stress and multilineage differentiation capacities compared with age-matched mdx MPCs. This effect may potentially be mediated by fibroblast growth factor overexpression and/or a reduction in telomerase activity. Our results demonstrate that the rapid disease progression in the dKO model is associated, at least in part, with MPC depletion. Therefore, alleviating MPC depletion could represent an approach to delay the onset of the histopathologies associated with DMD patients.

Epigenetics is the study of changes in gene expression or cellular phenotype caused by mechanisms other than changes in the underlying DNA sequence. It is widely accepted that cancer has genetic and epigenetic origins. The idea of epigenetic reprogramming of cancer cells by an embryonic microenvironment possesses potential interest from the prospect of both basic science and potential therapeutic strategies. Chick embryo extract (CEE) has been used for the successful expansion of many specific stem cells and has demonstrated the ability to facilitate DNA demethylation.The current study was conducted to compare the status of DNA methylation in highly metastatic and less metastatic osteosarcoma cells and to investigate whether CEE may affect the epigenetic regulation of tumor suppressor genes and thus change the metastatic phenotypes of highly metastatic osteosarcoma cells.K7M2 murine OS cells were treated with CEE to determine its potential effect on DNA methylation, cell apoptosis, and invasion capacity.Our current results suggest that the methylation status of tumor suppressor genes (p16, p53, and E-cadherin) is significantly greater in highly metastatic mouse ostoesarcoma K7M2 cells in comparison with less metastatic mouse osteosarcoma K12 cells. CEE treatment of K7M2 cells caused demethylation of p16, p53, and E-cadherin genes, upregulated their expression, and resulted in the reversion of metastatic phenotypes in highly metastatic osteosarcoma cells.CEE may promote the reversion of metastatic phenotypes of osteosarcoma cells and can be a helpful tool to study osteosarcoma tumor reversion by epigenetic reprogramming.Demethylation of tumor suppressor genes in osteosarcoma may represent a novel strategy to diminish the metastatic potential of this neoplasm. Further studies, both in vitro and in vivo, are warranted to evaluate the clinical feasibility of this approach as an adjuvant to current therapy.

The ongoing development of urbanization makes it increasingly necessary to map urban expansion over a longer term than ever. Long time series of remotely sensed images are useful data for understanding urban dynamic processes spatio-temporally, but they are difficult to utilize with traditional bi-temporal change detection techniques. In this article, a framework for mapping urban expansion from long Landsat time series is proposed based on trajectory analysis. Assuming that change indicator trajectories could reveal land-cover change trajectories, there are distinctive temporal signatures of different land-cover conversions in such trajectories that can be traced. Accordingly, ideal trajectories of other land-cover types converting to urban land are described. The entire observed trajectory was examined and fitted with ideal trajectories to detect areas that fit the description. This approach requires no single-date classification or extraction of urban land or bi-temporal change threshold determination, and it utilizes temporal information contained in the time series. We tested the method using a 7-year time series of Landsat Thematic Mapper TM and Enhanced Thematic Mapper Plus ETM+ imagery of an urban fringe area of Beijing, China, acquired between 1999 and 2011. The detection of stable urban land and new urban land achieved an overall accuracy of 83.30%, with a kappa coefficient of 0.7917.

Aircraft detection is one of the applications of high resolution remote-sensing images. Conventional method of aircraft detection use deep and complicated network, which needs highly computing cost. In this letter, an efficient and effective aircraft detection framework based on BOVW features and cascade AdaBoost classifier has been proposed. A variety of affine invariant features, which represent the complicate structure of aircraft, are extracted from sliding windows, and the direction estimation of aircraft is introduced to align the aircraft before detection. Besides, an accurate NMS algorithm is designed to make the target location more accurate. The proposed method is evaluated with recent advanced detection methods. The superior experimental outcome indicates that our framework achieves better accuracy as well as efficiency.

Aiming at the problem of objects in image recognition rectangle, but objects which are input into convolutional neural networks square, the object recognition model was put forward which was based on BING method to realize object estimate, used vectorization of convolutional neural networks to realize input square image in convolutional networks, therefore, built joint convolution neural networks, which achieve multiple size image input. Verified by experiments, the accuracy of multi-object image recognition was improved by 6.70% compared with single vectorization of convolutional neural networks. Therefore, image recognition method of joint convolutional neural networks can enhance the accuracy in image recognition, especially for target in rectangular shape.

We demonstrate high power, deep ultraviolet (DUV) conversion to 266 nm through frequency quadrupling of a nanosecond pulse width 1064 nm fiber master oscillator power amplifier (MOPA). The MOPA system uses an Yb-doped double-clad polarization-maintaining large mode area tapered fiber as the final gain stage to generate 0.5-mJ, 10 W, 1.7- ns single mode pulses at a repetition rate of 20 kHz with measured spectral bandwidth of 10.6 GHz (40 pm), and beam qualities of Mx 2=1.07 and My 2=1.03, respectively. Using LBO and BBO crystals for the second-harmonic generation (SHG) and fourth-harmonic generation (FHG), we have achieved 375 μJ (7.5 W) and 92.5 μJ (1.85 W) at wavelengths of 532 nm and 266 nm, respectively. To the best of our knowledge these are the highest narrowband infrared, green and UV pulse energies obtained to date from a fully spliced fiber amplifier. We also demonstrate high efficiency SHG and FHG with walk-off compensated (WOC) crystal pairs and tightly focused pump beam. An SHG efficiency of 75%, FHG efficiency of 47%, and an overall efficiency of 35% from 1064 nm to 266 nm are obtained.

Duchenne muscular dystrophy (DMD) is a degenerative muscle disorder characterized by the lack of dystrophin expression at the sarcolemma of muscle fibers. In addition, DMD patients acquire osteopenia, fragility fractures, and scoliosis indicating that a deficiency in skeletal homeostasis coexists but little is known about the effects of DMD on bone and other connective tissues within the musculoskeletal system. Recent evidence has emerged implicating adult stem cell dysfunction in DMD myopathogenesis. Given the common mesenchymal origin of muscle and bone, we sought to investigate bone and other musculoskeletal tissues in a DMD mouse model. Here, we report that dystrophin-utrophin double knockout (dko) mice exhibit a spectrum of degenerative changes, outside skeletal muscle, in bone, articular cartilage, and intervertebral discs, in addition to reduced lifespan, muscle degeneration, spinal deformity, and cardiomyopathy previously reported. We also report these mice to have a reduced capacity for bone healing and exhibit spontaneous heterotopic ossification in the hind limb muscles. Therefore, we propose the dko mouse as a model for premature musculoskeletal aging and posit that a similar phenomenon may occur in patients with DMD.

The developing logical process (LP)-based parallel and distributed discrete-event simulation (PDES) in the existing PDES programming environments is a difficult and time-consuming process. Event graph is a simple and powerful modelling formalism of discrete-event simulation, whereas this formalism does not support PDES. This article proposes an extension of the event graph to consider the communication of LPs via the events sent, which is called ‘extended event graph (EEG)’, and proposes an EEG-based modelling method for PDES. This modelling method shifts the focus of PDES development from writing code to building models, and the system implementation can be automatically and directly generated from EEG model. The experimental results show that EEG models can successfully execute in the parallel simulator, and this framework can effectively improve the PDES modelling activities.

In order to improve the accuracy of prediction for software defect data sets, competitive organization coevolutionary algorithm is presented and applied for dealing with the software defect data. During this algorithm, mechanism of competition is introduced into coevolutionary algorithm. Then leagues are formed based on the importance of attributes among them. And three evolution operators which are reduced operator, allied operators and disturbed operators are developed. Furthermore, both the importance of attributes and evaluation from competition are used for the calculation of fitness function. Finally, five data sets from NASA MDP(Metrics Data Program) were used to validate the algorithm. The experimental results show that the proposed algorithm is effective for software defect prediction.

A wide variety of myogenic cell sources have been used for repair of injured and diseased muscle including muscle stem cells, which can be isolated from skeletal muscle as a group of slow-adhering cells on a collagen-coated surface. The therapeutic use of muscle stem cells for improving muscle regeneration is promising; however, the effect of injury on their characteristics and engraftment potential has yet to be described. In the present study, slow-adhering stem cells (SASCs) from both laceration-injured and control noninjured skeletal muscles in mice were isolated and studied. Migration and proliferation rates, multidifferentiation potentials, and differences in gene expression in both groups of cells were compared in vitro. Results demonstrated that a larger population of SASCs could be isolated from injured muscle than from control noninjured muscle. In addition, SASCs derived from injured muscle demonstrated improved migration, a higher rate of proliferation and multidifferentiation, and increased expression of Notch1, STAT3, Msx1, and MMP2. Moreover, when transplanted into dystrophic muscle in MDX/SCID mice, SASCs from injured muscle generated greater engraftments with a higher capillary density than did SASCs from control noninjured muscle. These data suggest that traumatic injury may modify stem cell characteristics through trophic factors and improve the transplantation potential of SASCs in alleviating skeletal muscle injuries and diseases.

Wnt signaling plays a crucial role in regulating cell proliferation, differentiation and inducing cardiomyogenesis. Skeletal muscle-derived stem cells (MDSCs) have been shown to be multipotent; however, their potential to aid in the healing of the heart after myocardial infarction appears to be due to the paracrine effects they impart on the host environment. The goal of this study was to investigate whether Wnt11 could promote the differentiation of MDSCs into cardiomyocytes and enhance the repair of infarcted myocardium. MDSCs transduced with a lentivirus encoding for Wnt11 increased mRNA and protein expression of the early cardiac markers NK2 transcription factor related 5 (NKx2.5) and Connexin43 (Cx43) and also led to an increased expression of late-stage cardiac markers including: α, β-myosin heavy chain (MHC) and brain natriuretic protein (BNP) at the mRNA level, and MHC and Troponin I (TnI) at the protein level. We also observed that Wnt11 expression significantly enhanced c-jun N-terminal kinase activity in transduced MDSCs, and that some of the cells beat spontaneously but are not fully differentiated cardiomyocytes. Finally, lentivirus-Wnt11-transduced MDSCs showed greater survival and cardiac differentiation after being transplanted into acutely infarct-injured myocardium. These findings could one day lead to strategies that could be utilized in cardiomyoplasty treatments of myocardial infarction.

The polypeptide hormone relaxin has been proven to be effective in promoting both the remodeling and regeneration of various tissues, including cardiac muscle. In addition, our previous study demonstrated that relaxin is beneficial to skeletal muscle healing by both promoting muscle regeneration and preventing fibrosis formation. However, the molecular and cellular mechanisms of relaxin in regulating both myogenic cell differentiation and muscle healing process are still unclear. In this study, C2C12 mouse myoblasts and primary human myoblasts were treated with relaxin to investigate its potential effect in vitro; relaxin was also injected intramuscularly into the injured site of the mouse on the second day after injury to observe its function in vivo, especially in the aged muscle. Results showed that relaxin promoted myogenic differentiation, migration, and activation of matrix metalloproteinases (MMPs) of cultured myoblasts in vitro. In the injured muscle, relaxin administration promoted the activation of Pax7-positive skeletal muscle satellite cells and increased its local population compared with nontreated control muscles. Meanwhile, both angiogenesis and revascularization were increased, while the extended inflammatory reaction was repressed in the relaxin-treated injured muscle. Moreover, relaxin similarly promoted muscle healing in mice with aged muscle. These results revealed the multiple effects of relaxin in systematically improving muscle healing as well as its potential for clinical applications in patients with skeletal muscle injuries and diseases.

Fibrosis is the result of an excessive amount of fibrous connective tissue deposited into the extracellular matrix (ECM) space of damaged tissues from injury or disease. Collagens, particularly types I and III are the main constituents of the fibrotic scar tissue as well as a mixture of fibrotic cells. Severely fibrotic tissue will develop chronic healing problems resulting in tissue/organ dysfunction. More attention needs to be given to the fibrotic differentiation and related effects in bioengineered tissues. The current review provides an update on the mechanism behind fibrosis formation as well as technical measurements and preventions.

The limitation in successfully acquiring large populations of stem cell has impeded their application. A new method based on the dedifferentiation of adult somatic cells to generate induced multipotent stem cells would allow us to obtain a large amount of autologous stem cells for regenerative medicine. The current work was proposed to induce a sub-population of cells with characteristics of muscle stem cells from myoblasts through conditional treatment of transforming growth factor (TGF)-β(1) . Our results show that a lower concentration of TGF-β(1) is able to promote C2C12 myoblasts to express stem cell markers as well as to repress myogenic proteins, which involves a mechanism of dedifferentiation. Moreover, TGF-β(1) treatment promoted the proliferation-arrested C2C12 myoblasts to re-enter the S-phase. We also investigated the multi-differentiation potentials of the dedifferentiated cells. TGF-β(1) pre-treated C2C12 myoblasts were implanted into mice to repair dystrophic skeletal muscle or injured bone. In addition to the C2C12 myoblasts, similar effects of TGF-β(1) were also observed in the primary myoblasts of mice. Our results suggest that TGF-β(1) is effective as a molecular trigger for the dedifferentiation of skeletal muscle myoblasts and could be used to generate a large pool of progenitor cells that collectively behave as multipotent stem cell-like cells for regenerative medicine applications.

Matrix metalloproteinases (MMPs) are a group of proteases that belong to the metazincin family. These proteins consist of similar structures featuring a signaling peptide, a propeptide domain, a catalytic domain where the notable zinc ion binding site is found and a hinge region that binds to the C-terminal hemoplexin domain. MMPs can be produced by numerous cell types through secretion or localization to the cell membrane. While certain chemical compounds have been known to generally inhibit MMPs, naturally occurring proteins known as tissue inhibitors of metalloproteinases (TIMPs) effectively interact with MMPs to modify their biological roles. MMPs are very important enzymes that actively participate in remodeling the extracellular matrix by degrading certain constituents, along with promoting cell proliferation, migration, differentiation, apoptosis and angiogenesis. In normal adult tissue, they are almost undetectable; however, when perturbed through injury, disease or pregnancy, they have elevated expression. The goal of this review is to identify new experimental findings that have provided further insight into the role of MMPs in skeletal muscle, nerve and dermal tissue, as well as in the liver, heart and kidneys. Increased expression of MMPs can improve the regeneration potential of wounds; however, an imbalance between MMP and TIMP expression can prove to be destructive for afflicted tissues.

We review our recent results obtained on an AlN/GaN-based high-electron-mobility transistor. The temperature of the electrons drifting under a relatively-high electric field is significantly higher than the lattice temperature (i.e., the hot electrons are generated). These hot electrons are produced through the Frohlich interaction between the drifting electrons and long-lived longitudinal-optical phonons. By fitting electric field vs. electron temperature deduced from the measurements of photoluminescence spectra to a theoretical model, we have deduced the longitudinal-optical-phonon emission time for each electron is to be on the order of 100 fs. We have also measured the decay time constant for LO phonons to be about 4.2 ps. An electric field present in a GaN/AlN heterostructure can bring both the first-order and second-order Raman scattering processes into strong resonances. The resonant Stokes and anti-Stokes Raman scattering results in the increase and decrease of non-equilibrium longitudinal-optical phonon temperatures, respectively. Moreover, the phonon temperature measured from the Raman scattering is increased with an applied electric field at a much higher rate than the lattice temperature due to the presence of field-induced non-equilibrium longitudinal-optical phonons.

We review the progress made by us on the exploration of the fundamental limits to terahertz (THz) generation from several semiconductor electrooptic materials. Through the measurements of the THz output versus the pump beam in terms of incident angle, polarization, azithumal angle, and pump intensity, we have demonstrated that we can precisely determine the contributions made by the optical rectification and photocurrent surge. When a material is pumped below its bandgap, optical rectification is always the mechanism for the THz generation. Above the bandgap, however, these two mechanisms often compete with each other, depending on the material characteristics and pump intensity. At a sufficiently high pump intensity, optical rectification usually becomes the dominant mechanism for a second-order nonlinear material. Our analysis indicates that second-order nonlinear coefficients are resonantly enhanced when a material is pumped above its bandgap. In such a case, the THz output power and normalized conversion efficiency can be dramatically increased. We have also illustrated that, for some materials, two-photon absorption can be one of the fundamental limits to the THz generation.

We have investigated power scaling for the efficient generation of the broadband terahertz (THz) pulses. These THz short pulses are converted from ultrafast laser pulses propagating in a class of semiconductor electrooptic materials. By measuring the dependence of the THz output on the pump beam in terms of incident angle, polarization, azimuthal angle, and pump intensity, we have precisely determined the contributions made by optical rectification, drift of carriers under a surface or external field, and photo-Dember effect. When a second-order nonlinear material is pumped below its bandgap, optical rectification is always the mechanism for the THz generation. Above the bandgap, however, the three mechanisms mentioned earlier often compete with one another, depending on the material characteristics and pump intensity. At a sufficiently high pump intensity, optical rectification usually becomes the dominant mechanism for a second-order nonlinear material. Our analysis indicates that second-order nonlinear coefficients can be resonantly enhanced when a material is pumped above its bandgap. In such a case, the THz output power and normalized conversion efficiency can be dramatically increased. We have also analyzed how the THz generation is affected by some competing processes such as two-photon absorption.

Although we recognize the many advantages of improved musculoskeletal health, we also note that our ability to sustain this health and to maintain quality of life in an aging population is currently deficient. However, global efforts have produced numerous advances in tissue engineering and regenerative medicine that will collectively serve to fill this deficiency in the near future. The purpose of this review is to highlight our current knowledge, to outline our recent advances, and to discuss the evolving paradigms in skeletal muscle injury and repair.

Skeletal muscle atrophy in cancer cachexia is mediated by the interaction between muscle stem cells and various tumor factors. Although Notch signaling has been known as a key regulator of both cancer development and muscle stem cell activity, the potential involvement of Notch signaling in cancer cachexia and concomitant muscle atrophy has yet to be elucidated. The murine K7M2 osteosarcoma cell line was used to generate an orthotopic model of sarcoma-associated cachexia, and the role of Notch signaling was evaluated. Skeletal muscle atrophy was observed in the sarcoma-bearing mice, and Notch signaling was highly active in both tumor tissues and the atrophic skeletal muscles. Systemic inhibition of Notch signaling reduced muscle atrophy.In vitrococulture of osteosarcoma cells with muscle-derived stem cells (MDSCs) isolated from normal mice resulted in decreased myogenic potential of MDSCs, while the application of Notch inhibitor was able to rescue this repressed myogenic potential. We further observed that Notch-activating factors reside in the exosomes of osteosarcoma cells, which activate Notch signaling in MDSCs and subsequently repress myogenesis. Our results revealed that signaling between tumor and muscle via the Notch pathway may play an important role in mediating the skeletal muscle atrophy seen in cancer cachexia.

We have demonstrated mJ pulse energy with nanosecond pulses, narrow linewidth, and single-mode beam quality operation in a master oscillator power amplifier (MOPA) fiber laser system using an Yb-doped polarization maintaining tapered amplifier.

We have reviewed mechanisms for the efficient conversion of the broadband terahertz (THz) pulses from ultrafast laser pulses propagating in semiconductor electro-optic materials. By measuring the behaviors of the THz output versus the pump beam in terms of incident angle, polarization, and azimuthal angle, we have demonstrated that we can precisely determine the contributions made by optical rectification and photocurrent surge. When a material is pumped below its bandgap, optical rectification is always the mechanism for the THz generation. Above the bandgap, however, these two mechanisms often compete with each other, depending on the material characteristics and pump intensity. At a sufficiently high pump intensity, optical rectification usually becomes the dominant mechanism for a second-order nonlinear material. Our analysis indicates that second-order nonlinear coefficients can be resonantly enhanced when a material is pumped above its bandgap. In such a case, the THz output power and normalized conversion efficiency can be greatly enhanced. We have also analyzed how the THz generation is affected by some competing processes such as two-photon absorption.

We review our recent results on the investigation of carrier dynamics of semiconductor nanostructures, i.e., dot-in-a-well. We introduced a technique based on the measurement of time-resolved differential photoluminescence spectra induced by subpicosecond pump and probe laser pulses. In this technique, the temporal resolution was achieved by adjusting the temporal delay between the pump and probe pulses. Using such a new technique, we measured the exciton decay times and then studied the dependences of integrated photoluminescence intensity and photoluminescence linewidth on temperature in InAs quantum dots embedded in InGaAs/GaAs quantum wells. We gave consistent interpretations to our experimental results.

We recently discovered a novel population of stem cells from the injured murine skeletal muscle. These injury induced muscle-derived stem cell-like cells (iMuSCs) are partially reprogrammed from differentiated myogenic cells and display a pluripotent-like state. The iMuSCs exhibit stem cell properties including the ability to differentiate into multiple lineages, such as neurogenic and myogenic differentiations; they also display a superior migration capacity that demonstrating a strong ability of muscle engraftment in vivo. IMuSCs express several pluripotent and myogenic stem cell markers; have the capability to form embryoid bodies and teratomas and can differentiate into all three germ layers. Moreover, blastocyst microinjection showed that the iMuSCs contributed to chimeric embryos but could not complete germline transmission. Our results indicate that the iMuSCs are in a partially reprogrammed state of pluripotency, which are generated by the microenvironment of injured skeletal muscle.

This article puts forward a kind of huge amounts of multi-object image recognition method -- BVCNN. Firstly, BING method is used to recognize images, which greatly reduces the time of estimating image targets, and makes it possible that quickly identify multiple target images, compared to traditional convolution neural networks only achieving single target image recognition, Secondly, vectorization of deep convolutional neural networks is used for deep learning of characteristics in local image and recognition, which speeds up network training and testing, thirdly, using the context information in multi-object image classification, to a certain extent, helps to distinguish individual of similar characteristics according to environment, improving the multi-object image recognition accuracy. According to experiments, identifying a single image by this model only need less than 1 s, and this model can be used for image information fusion.

Single-clad and double-clad Yb:YAG crystalline fiber waveguides (CFWs) have been prepared with Adhesive-Free Bonding (AFB®) technology. By using a fiber coupled laser diode as pump source, a single-mode laser with near diffraction limited beam quality M 2 =1.02 has been demonstrated in a double-clad CFW. The laser output power and efficiency are 13.2 W and 34%, respectively. In a single-clad CFW, core pumping was used. The laser output has top-hat beam profile. An output power of 28 W and a slope efficiency of 78% have been achieved respectively. Keywords: Crystalline fiber, waveguide, laser, master oscillator power amplifier, adhesive-free bond 1. INTRODUCTION There is great interest in making rare-earth (RE) doped YAG crystalline fiber lasers due to their higher power scalability compared to glass fibers [1]. However, current fiber growth (or pulling) techniques, such as laser heated pedestal growth (LHPG) [2-4] and micro pulling down [5], have not yet been successful in producing low loss, double-clad, or even single-clad fully crystalline fibers. As an alternative to conventional fiber pulling technologies, Onyx Optics’ well established Adhesive-Free Bond (AFB®) technology circumvents the problems with the fabrication of low-loss crystalline fiber waveguides (CFW) [6-8]. In the present work , we report on the first laser diode (LD) cladding pumped single-mode 1030-nm laser in a double-clad Yb:YAG CF W with a near diffraction-limited beam quality of M