Sample records for scatter correction msc
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Pan, Sha-sha; Huang, Fu-rong; Xiao, Chi; Xian, Rui-yi; Ma, Zhi-guo
2015-10-01
To explore rapid reliable methods for detection of Epicarpium citri grandis (ECG), the experiment using Fourier Transform Attenuated Total Reflection Infrared Spectroscopy (FTIR/ATR) and Fluorescence Spectrum Imaging Technology combined with Multilayer Perceptron (MLP) Neural Network pattern recognition, for the identification of ECG, and the two methods are compared. Infrared spectra and fluorescence spectral images of 118 samples, 81 ECG and 37 other kinds of ECG, are collected. According to the differences in tspectrum, the spectra data in the 550-1 800 cm(-1) wavenumber range and 400-720 nm wavelength are regarded as the study objects of discriminant analysis. Then principal component analysis (PCA) is applied to reduce the dimension of spectroscopic data of ECG and MLP Neural Network is used in combination to classify them. During the experiment were compared the effects of different methods of data preprocessing on the model: multiplicative scatter correction (MSC), standard normal variable correction (SNV), first-order derivative(FD), second-order derivative(SD) and Savitzky-Golay (SG). The results showed that: after the infrared spectra data via the Savitzky-Golay (SG) pretreatment through the MLP Neural Network with the hidden layer function as sigmoid, we can get the best discrimination of ECG, the correct percent of training set and testing set are both 100%. Using fluorescence spectral imaging technology, corrected by the multiple scattering (MSC) results in the pretreatment is the most ideal. After data preprocessing, the three layers of the MLP Neural Network of the hidden layer function as sigmoid function can get 100% correct percent of training set and 96.7% correct percent of testing set. It was shown that the FTIR/ATR and fluorescent spectral imaging technology combined with MLP Neural Network can be used for the identification study of ECG and has the advantages of rapid, reliable effect.
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Prediction of soil organic carbon in a coal mining area by Vis-NIR spectroscopy.
Sun, Wenjuan; Li, Xinju; Niu, Beibei
2018-01-01
Coal mining has led to increasingly serious land subsidence, and the reclamation of the subsided land has become a hot topic of concern for governments and scholars. Soil quality of reclaimed land is the key indicator to the evaluation of the reclamation effect; hence, rapid monitoring and evaluation of reclaimed land is of great significance. Visible-near infrared (Vis-NIR) spectroscopy has been shown to be a rapid, timely and efficient tool for the prediction of soil organic carbon (SOC). In this study, 104 soil samples were collected from the Baodian mining area of Shandong province. Vis-NIR reflectance spectra and soil organic carbon content were then measured under laboratory conditions. The spectral data were first denoised using the Savitzky-Golay (SG) convolution smoothing method or the multiple scattering correction (MSC) method, after which the spectral reflectance (R) was subjected to reciprocal, reciprocal logarithm and differential transformations to improve spectral sensitivity. Finally, regression models for estimating the SOC content by the spectral data were constructed using partial least squares regression (PLSR). The results showed that: (1) The SOC content in the mining area was generally low (at the below-average level) and exhibited great variability. (2) The spectral reflectance increased with the decrease of soil organic carbon content. In addition, the sensitivity of the spectrum to the change in SOC content, especially that in the near-infrared band of the original reflectance, decreased when the SOC content was low. (3) The modeling results performed best when the spectral reflectance was preprocessed by Savitzky-Golay (SG) smoothing coupled with multiple scattering correction (MSC) and first-order differential transformation (modeling R2 = 0.86, RMSE = 2.00 g/kg, verification R2 = 0.78, RMSE = 1.81 g/kg, and RPD = 2.69). In addition, the first-order differential of R combined with SG, MSC with R, SG together with MSC and R also produced better modeling results than other pretreatment combinations. Vis-NIR modeling with specific spectral preprocessing methods could predict SOC content effectively.
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Zu, Qin; Zhao, Chun-Jiang; Deng, Wei; Wang, Xiu
2013-05-01
The automatic identification of weeds forms the basis for precision spraying of crops infest. The canopy spectral reflectance within the 350-2 500 nm band of two strains of cabbages and five kinds of weeds such as barnyard grass, setaria, crabgrass, goosegrass and pigweed was acquired by ASD spectrometer. According to the spectral curve characteristics, the data in different bands were compressed with different levels to improve the operation efficiency. Firstly, the spectrum was denoised in accordance with the different order of multiple scattering correction (MSC) method and Savitzky-Golay (SG) convolution smoothing method set by different parameters, then the model was built by combining the principal component analysis (PCA) method to extract principal components, finally all kinds of plants were classified by using the soft independent modeling of class analogy (SIMCA) taxonomy and the classification results were compared. The tests results indicate that after the pretreatment of the spectral data with the method of the combination of MSC and SG set with 3rd order, 5th degree polynomial, 21 smoothing points, and the top 10 principal components extraction using PCA as a classification model input variable, 100% correct classification rate was achieved, and it is able to identify cabbage and several kinds of common weeds quickly and nondestructively.
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[Spectral scatter correction of coal samples based on quasi-linear local weighted method].
Lei, Meng; Li, Ming; Ma, Xiao-Ping; Miao, Yan-Zi; Wang, Jian-Sheng
2014-07-01
The present paper puts forth a new spectral correction method based on quasi-linear expression and local weighted function. The first stage of the method is to search 3 quasi-linear expressions to replace the original linear expression in MSC method, such as quadratic, cubic and growth curve expression. Then the local weighted function is constructed by introducing 4 kernel functions, such as Gaussian, Epanechnikov, Biweight and Triweight kernel function. After adding the function in the basic estimation equation, the dependency between the original and ideal spectra is described more accurately and meticulously at each wavelength point. Furthermore, two analytical models were established respectively based on PLS and PCA-BP neural network method, which can be used for estimating the accuracy of corrected spectra. At last, the optimal correction mode was determined by the analytical results with different combination of quasi-linear expression and local weighted function. The spectra of the same coal sample have different noise ratios while the coal sample was prepared under different particle sizes. To validate the effectiveness of this method, the experiment analyzed the correction results of 3 spectral data sets with the particle sizes of 0.2, 1 and 3 mm. The results show that the proposed method can eliminate the scattering influence, and also can enhance the information of spectral peaks. This paper proves a more efficient way to enhance the correlation between corrected spectra and coal qualities significantly, and improve the accuracy and stability of the analytical model substantially.
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Liang, Xue; Ji, Hai-yan; Wang, Peng-xin; Rao, Zhen-hong; Shen, Bing-hui
2010-01-01
Preprocess method of multiplicative scatter correction (MSC) was used to reject noises in the original spectra produced by the environmental physical factor effectively, then the principal components of near-infrared spectroscopy were calculated by nonlinear iterative partial least squares (NIPALS) before building the back propagation artificial neural networks method (BP-ANN), and the numbers of principal components were calculated by the method of cross validation. The calculated principal components were used as the inputs of the artificial neural networks model, and the artificial neural networks model was used to find the relation between chlorophyll in winter wheat and reflective spectrum, which can predict the content of chlorophyll in winter wheat. The correlation coefficient (r) of calibration set was 0.9604, while the standard deviation (SD) and relative standard deviation (RSD) was 0.187 and 5.18% respectively. The correlation coefficient (r) of predicted set was 0.9600, and the standard deviation (SD) and relative standard deviation (RSD) was 0.145 and 4.21% respectively. It means that the MSC-ANN algorithm can reject noises in the original spectra produced by the environmental physical factor effectively and set up an exact model to predict the contents of chlorophyll in living leaves veraciously to replace the classical method and meet the needs of fast analysis of agricultural products.
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NASA Astrophysics Data System (ADS)
Mao, Zhiyi; Shan, Ruifeng; Wang, Jiajun; Cai, Wensheng; Shao, Xueguang
2014-07-01
Polyphenols in plant samples have been extensively studied because phenolic compounds are ubiquitous in plants and can be used as antioxidants in promoting human health. A method for rapid determination of three phenolic compounds (chlorogenic acid, scopoletin and rutin) in plant samples using near-infrared diffuse reflectance spectroscopy (NIRDRS) is studied in this work. Partial least squares (PLS) regression was used for building the calibration models, and the effects of spectral preprocessing and variable selection on the models are investigated for optimization of the models. The results show that individual spectral preprocessing and variable selection has no or slight influence on the models, but the combination of the techniques can significantly improve the models. The combination of continuous wavelet transform (CWT) for removing the variant background, multiplicative scatter correction (MSC) for correcting the scattering effect and randomization test (RT) for selecting the informative variables was found to be the best way for building the optimal models. For validation of the models, the polyphenol contents in an independent sample set were predicted. The correlation coefficients between the predicted values and the contents determined by high performance liquid chromatography (HPLC) analysis are as high as 0.964, 0.948 and 0.934 for chlorogenic acid, scopoletin and rutin, respectively.
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Dorwart, Michael R; Wray, Robin; Brautigam, Chad A; Jiang, Youxing; Blount, Paul
2010-12-07
While the bacterial mechanosensitive channel of large conductance (MscL) is the best studied biological mechanosensor and serves as a paradigm for how a protein can sense and respond to membrane tension, the simple matter of its oligomeric state has led to debate, with models ranging from tetramers to hexamers. Indeed, two different oligomeric states of the bacterial mechanosensitive channel MscL have been resolved by X-ray crystallography: The M. tuberculosis channel (MtMscL) is a pentamer, while the S. aureus protein (SaMscL) forms a tetramer. Because several studies suggest that, like MtMscL, the E. coli MscL (EcoMscL) is a pentamer, we re-investigated the oligomeric state of SaMscL. To determine the structural organization of MscL in the cell membrane we developed a disulfide-trapping approach. Surprisingly, we found that virtually all SaMscL channels in vivo are pentameric, indicating this as the physiologically relevant and functional oligomeric state. Complementing our in vivo results, we purified SaMscL and assessed its oligomeric state using three independent approaches (sedimentation equilibrium centrifugation, crosslinking, and light scattering) and established that SaMscL is a pentamer when solubilized in Triton X-100 and C(8)E(5) detergents. However, performing similar experiments on SaMscL solubilized in LDAO, the detergent used in the crystallographic study, confirmed the tetrameric oligomerization resolved by X-ray crystallography. We further demonstrate that this stoichiometric shift is reversible by conventional detergent exchange experiments. Our results firmly establish the pentameric organization of SaMscL in vivo. Furthermore they demonstrate that detergents can alter the subunit stoichiometry of membrane protein complexes in vitro; thus, in vivo assays are necessary to firmly establish a membrane protein's true functionally relevant oligomeric state.
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Exosomes of human placenta-derived mesenchymal stem cells stimulate angiogenesis.
Komaki, Motohiro; Numata, Yuri; Morioka, Chikako; Honda, Izumi; Tooi, Masayuki; Yokoyama, Naoki; Ayame, Hirohito; Iwasaki, Kengo; Taki, Atsuko; Oshima, Noriko; Morita, Ikuo
2017-10-03
The therapeutic potential of mesenchymal stem cells (MSCs) may be attributed partly to humoral factors such as growth factors, cytokines, and chemokines. Human term placental tissue-derived MSCs (PlaMSCs), or conditioned medium left over from cultures of these cells, have been reported to enhance angiogenesis. Recently, the exosome, which can transport a diverse suite of macromolecules, has gained attention as a novel intercellular communication tool. However, the potential role of the exosome in PlaMSC therapeutic action is not well understood. The purpose of this study was to evaluate PlaMSC-derived exosome angiogenesis promotion in vitro and in vivo. MSCs were isolated from human term placental tissue by enzymatic digestion. Conditioned medium was collected after 48-h incubation in serum-free medium (PlaMSC-CM). Angiogenic factors present in PlaMSC-CM were screened by a growth factor array. Exosomes were prepared by ultracentrifugation of PlaMSC-CM, and confirmed by transmission electron microscopy, dynamic light scattering, and western blot analyses. The proangiogenic activity of PlaMSC-derived exosomes (PlaMSC-exo) was assessed using an endothelial tube formation assay, a cell migration assay, and reverse transcription-PCR analysis. The in-vivo angiogenic activity of PlaMSC-exo was evaluated using a murine auricle ischemic injury model. PlaMSC-CM contained both angiogenic and angiostatic factors, which enhanced endothelial tube formation. PlaMSC-exo were incorporated into endothelial cells; these exosomes stimulated both endothelial tube formation and migration, and enhanced angiogenesis-related gene expression. Laser Doppler blood flow analysis showed that PlaMSC-exo infusion also enhanced angiogenesis in an in-vivo murine auricle ischemic injury model. PlaMSC-exo enhanced angiogenesis in vitro and in vivo, suggesting that exosomes play a role in the proangiogenic activity of PlaMSCs. PlaMSC-exo may be a novel therapeutic approach for treating ischemic diseases.
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Leaf Chlorophyll Content Estimation of Winter Wheat Based on Visible and Near-Infrared Sensors.
Zhang, Jianfeng; Han, Wenting; Huang, Lvwen; Zhang, Zhiyong; Ma, Yimian; Hu, Yamin
2016-03-25
The leaf chlorophyll content is one of the most important factors for the growth of winter wheat. Visual and near-infrared sensors are a quick and non-destructive testing technology for the estimation of crop leaf chlorophyll content. In this paper, a new approach is developed for leaf chlorophyll content estimation of winter wheat based on visible and near-infrared sensors. First, the sliding window smoothing (SWS) was integrated with the multiplicative scatter correction (MSC) or the standard normal variable transformation (SNV) to preprocess the reflectance spectra images of wheat leaves. Then, a model for the relationship between the leaf relative chlorophyll content and the reflectance spectra was developed using the partial least squares (PLS) and the back propagation neural network. A total of 300 samples from areas surrounding Yangling, China, were used for the experimental studies. The samples of visible and near-infrared spectroscopy at the wavelength of 450,900 nm were preprocessed using SWS, MSC and SNV. The experimental results indicate that the preprocessing using SWS and SNV and then modeling using PLS can achieve the most accurate estimation, with the correlation coefficient at 0.8492 and the root mean square error at 1.7216. Thus, the proposed approach can be widely used for winter wheat chlorophyll content analysis.
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Fan, Shu-xiang; Huang, Wen-qian; Li, Jiang-bo; Zhao, Chun-jiang; Zhang, Bao-hua
2014-08-01
To improve the precision and robustness of the NIR model of the soluble solid content (SSC) on pear. The total number of 160 pears was for the calibration (n=120) and prediction (n=40). Different spectral pretreatment methods, including standard normal variate (SNV) and multiplicative scatter correction (MSC) were used before further analysis. A combination of genetic algorithm (GA) and successive projections algorithm (SPA) was proposed to select most effective wavelengths after uninformative variable elimination (UVE) from original spectra, SNV pretreated spectra and MSC pretreated spectra respectively. The selected variables were used as the inputs of least squares-support vector machine (LS-SVM) model to build models for de- termining the SSC of pear. The results indicated that LS-SVM model built using SNVE-UVE-GA-SPA on 30 characteristic wavelengths selected from full-spectrum which had 3112 wavelengths achieved the optimal performance. The correlation coefficient (Rp) and root mean square error of prediction (RMSEP) for prediction sets were 0.956, 0.271 for SSC. The model is reliable and the predicted result is effective. The method can meet the requirement of quick measuring SSC of pear and might be important for the development of portable instruments and online monitoring.
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NASA Astrophysics Data System (ADS)
Suzuki, Yusuke; Maruo, Katsuhiko; Zhang, Alice W.; Shimogaki, Kazushige; Ogawa, Hideto; Hirayama, Fumiya
2012-01-01
Bacterial contamination of blood products is one of the most frequent infectious complications of transfusion. Since glucose levels in blood supplies decrease as bacteria proliferate, it should be possible to detect the presence of bacterial contamination by measuring the glucose concentrations in the blood components. Hence this study is aimed to serve as a preliminary study for the nondestructive measurement of glucose level in transfusion blood. The glucose concentrations in red blood cell (RBC) samples were predicted using near-infrared diffuse-reflectance spectroscopy in the 1350 to 1850 nm wavelength region. Furthermore, the effects of donor, hematocrit level, and temperature variations among the RBC samples were observed. Results showed that the prediction performance of a dataset which contained samples that differed in all three parameters had a standard error of 29.3 mg/dL. Multiplicative scatter correction (MSC) preprocessing method was also found to be effective in minimizing the variations in scattering patterns created by various sample properties. The results suggest that the diffuse-reflectance spectroscopy may provide another avenue for the detection of bacterial contamination in red cell concentrations (RCC) products.
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Tension-activated channels in the mechanism of osmotic fitness in Pseudomonas aeruginosa
Rowe, Ian; Schams, Anthony; Mayhew, Christina
2017-01-01
Pseudomonas aeruginosa (PA) is an opportunistic pathogen with an exceptional ability to adapt to a range of environments. Part of its adaptive potential is the ability to survive drastic osmolarity changes. Upon a sudden dilution of external medium, such as during exposure to rain, bacteria evade mechanical rupture by engaging tension-activated channels that act as osmolyte release valves. In this study, we compare fast osmotic permeability responses in suspensions of wild-type PA and Escherichia coli (EC) strains in stopped-flow experiments and provide electrophysiological descriptions of osmotic-release channels in PA. Using osmotic dilution experiments, we first show that PA tolerates a broader range of shocks than EC. We record the kinetics of cell equilibration reported by light scattering responses to osmotic up- and down-shocks. PA exhibits a lower water permeability and faster osmolyte release rates during large osmotic dilutions than EC, which correlates with better survival. To directly characterize the PA tension-activated channels, we generate giant spheroplasts from this microorganism and record current responses in excised patches. Unlike EC, which relies primarily on two types of channels, EcMscS and EcMscL, to generate a distinctive two-wave pressure ramp response, PA exhibits a more gradual response that is dominated by MscL-type channels. Genome analysis, cloning, and expression reveal that PA possesses one MscL-type (PaMscL) and two MscS-type (PaMscS-1 and 2) proteins. In EC spheroplasts, both PaMscS channels exhibit a slightly earlier activation by pressure compared with EcMscS. Unitary currents reveal that PaMscS-2 has a smaller conductance, higher anionic preference, stronger inactivation, and slower recovery compared with PaMscS-1. We conclude that PA relies on MscL as the major valve defining a high rate of osmolyte release sufficient to curb osmotic swelling under extreme shocks, but it still requires MscS-type channels with a strong propensity to inactivation to properly terminate massive permeability response. PMID:28424229
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[Research on spectra recognition method for cabbages and weeds based on PCA and SIMCA].
Zu, Qin; Deng, Wei; Wang, Xiu; Zhao, Chun-Jiang
2013-10-01
In order to improve the accuracy and efficiency of weed identification, the difference of spectral reflectance was employed to distinguish between crops and weeds. Firstly, the different combinations of Savitzky-Golay (SG) convolutional derivation and multiplicative scattering correction (MSC) method were applied to preprocess the raw spectral data. Then the clustering analysis of various types of plants was completed by using principal component analysis (PCA) method, and the feature wavelengths which were sensitive for classifying various types of plants were extracted according to the corresponding loading plots of the optimal principal components in PCA results. Finally, setting the feature wavelengths as the input variables, the soft independent modeling of class analogy (SIMCA) classification method was used to identify the various types of plants. The experimental results of classifying cabbages and weeds showed that on the basis of the optimal pretreatment by a synthetic application of MSC and SG convolutional derivation with SG's parameters set as 1rd order derivation, 3th degree polynomial and 51 smoothing points, 23 feature wavelengths were extracted in accordance with the top three principal components in PCA results. When SIMCA method was used for classification while the previously selected 23 feature wavelengths were set as the input variables, the classification rates of the modeling set and the prediction set were respectively up to 98.6% and 100%.
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Siniatchkin, Michael; Moeller, Friederike; Jacobs, Julia; Stephani, Ulrich; Boor, Rainer; Wolff, Stephan; Jansen, Olav; Siebner, Hartwig; Scherg, Michael
2007-09-01
The ballistocardiogram (BCG) represents one of the most prominent sources of artifacts that contaminate the electroencephalogram (EEG) during functional MRI. The BCG artifacts may affect the detection of interictal epileptiform discharges (IED) in patients with epilepsy, reducing the sensitivity of the combined EEG-fMRI method. In this study we improved the BCG artifact correction using a multiple source correction (MSC) approach. On the one hand, a source analysis of the IEDs was applied to the EEG data obtained outside the MRI scanner to prevent the distortion of EEG signals of interest during the correction of BCG artifacts. On the other hand, the topographies of the BCG artifacts were defined based on the EEG recorded inside the scanner. The topographies of the BCG artifacts were then added to the surrogate model of IED sources and a combined source model was applied to the data obtained inside the scanner. The artifact signal was then subtracted without considerable distortion of the IED topography. The MSC approach was compared with the traditional averaged artifact subtraction (AAS) method. Both methods reduced the spectral power of BCG-related harmonics and enabled better detection of IEDs. Compared with the conventional AAS method, the MSC approach increased the sensitivity of IED detection because the IED signal was less attenuated when subtracting the BCG artifacts. The proposed MSC method is particularly useful in situations in which the BCG artifact is spatially correlated and time-locked with the EEG signal produced by the focal brain activity of interest.
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Croker, Denise M; Hennigan, Michelle C; Maher, Anthony; Hu, Yun; Ryder, Alan G; Hodnett, Benjamin K
2012-04-07
Diffraction and spectroscopic methods were evaluated for quantitative analysis of binary powder mixtures of FII(6.403) and FIII(6.525) piracetam. The two polymorphs of piracetam could be distinguished using powder X-ray diffraction (PXRD), Raman and near-infrared (NIR) spectroscopy. The results demonstrated that Raman and NIR spectroscopy are most suitable for quantitative analysis of this polymorphic mixture. When the spectra are treated with the combination of multiplicative scatter correction (MSC) and second derivative data pretreatments, the partial least squared (PLS) regression model gave a root mean square error of calibration (RMSEC) of 0.94 and 0.99%, respectively. FIII(6.525) demonstrated some preferred orientation in PXRD analysis, making PXRD the least preferred method of quantification. Copyright © 2012 Elsevier B.V. All rights reserved.
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View of Mission Control Center during the Apollo 13 oxygen cell failure
NASA Technical Reports Server (NTRS)
1970-01-01
Mrs. Mary Haise receives an explanation of the revised flight plan of the Apollo 13 mission from Astronaut Gerald P. Carr in the Viewing Room of Mission Control Center, bldg 30, Manned Spacecraft Center (MSC). Her husband, Astronaut Fred W. Haise Jr., was joining the fellow crew members in making corrections in their spacecraft following discovery of an oxygen cell failure several hours earlier (34900); Dr. Charles A. Berry, Director of Medical Research and Operations Directorate at MSC, converses with Mrs. Marilyn Lovell in the Viewing Room of Mission Control Center. Mrs. Lovell's husband, Astronaut James A. Lovell Jr., was busily making corrections inside the spacecraft following discovery of an oxygen cell failure several hours earlier (34901).
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Porada, Christopher D.; Sanada, Chad; Kuo, Chung-Jung; Colletti, Evan; Mandeville, Walter; Hasenau, John; Zanjani, Esmail D.; Moot, Robert; Doering, Christopher; Spencer, H. Trent; Almeida-Porada, Graça
2011-01-01
We recently re-established a line of sheep that accurately mimics the clinical symptoms and genetics of severe hemophilia A (HA). Herein, we tested a novel, non-ablative transplant therapy in 2 pediatric HA animals. Paternal mesenchymal stem cells (MSC) were transduced with a porcine FVIII-encoding lentivector, and transplanted via the intraperitoneal route, without preconditioning. At the time of transplantation, these animals had received multiple hFVIII treatments for various spontaneous bleeds, and had developed debilitating hemarthroses which produced severe defects in posture and gait. Transplantation of transduced MSC resolved all existent hemarthroses, and spontaneous bleeds ceased. Damaged joints recovered fully; the animals regained normal posture and gait and resumed normal activity. Despite achieving factor-independence, a sharp rise in pre-existent Bethesda titers occurred following transplantation, decreasing the effectiveness and duration of therapy. Post-mortem examination revealed widespread engraftment, with MSC present within the lung, liver, intestine, and thymus, but particularly within joints affected at the time of transplantation, suggesting MSC homed to sites of ongoing injury/inflammation to release FVIII, explaining the dramatic improvement in hemarthrotic joints. In summary, this novel, non-ablative MSC transplantation was straightforward, safe, and converted life-threatening, debilitating HA to a moderate phenotype in a large animal model. PMID:21906573
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Dou, Ying; Mi, Hong; Zhao, Lingzhi; Ren, Yuqiu; Ren, Yulin
2006-09-01
The application of the second most popular artificial neural networks (ANNs), namely, the radial basis function (RBF) networks, has been developed for quantitative analysis of drugs during the last decade. In this paper, the two components (aspirin and phenacetin) were simultaneously determined in compound aspirin tablets by using near-infrared (NIR) spectroscopy and RBF networks. The total database was randomly divided into a training set (50) and a testing set (17). Different preprocessing methods (standard normal variate (SNV), multiplicative scatter correction (MSC), first-derivative and second-derivative) were applied to two sets of NIR spectra of compound aspirin tablets with different concentrations of two active components and compared each other. After that, the performance of RBF learning algorithm adopted the nearest neighbor clustering algorithm (NNCA) and the criterion for selection used a cross-validation technique. Results show that using RBF networks to quantificationally analyze tablets is reliable, and the best RBF model was obtained by first-derivative spectra.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Chen, Xi; Mou, Xuanqin; Nishikawa, Robert M.
Purpose: Small calcifications are often the earliest and the main indicator of breast cancer. Dual-energy digital mammography (DEDM) has been considered as a promising technique to improve the detectability of calcifications since it can be used to suppress the contrast between adipose and glandular tissues of the breast. X-ray scatter leads to erroneous calculations of the DEDM image. Although the pinhole-array interpolation method can estimate scattered radiations, it requires extra exposures to measure the scatter and apply the correction. The purpose of this work is to design an algorithmic method for scatter correction in DEDM without extra exposures.Methods: In thismore » paper, a scatter correction method for DEDM was developed based on the knowledge that scattered radiation has small spatial variation and that the majority of pixels in a mammogram are noncalcification pixels. The scatter fraction was estimated in the DEDM calculation and the measured scatter fraction was used to remove scatter from the image. The scatter correction method was implemented on a commercial full-field digital mammography system with breast tissue equivalent phantom and calcification phantom. The authors also implemented the pinhole-array interpolation scatter correction method on the system. Phantom results for both methods are presented and discussed. The authors compared the background DE calcification signals and the contrast-to-noise ratio (CNR) of calcifications in the three DE calcification images: image without scatter correction, image with scatter correction using pinhole-array interpolation method, and image with scatter correction using the authors' algorithmic method.Results: The authors' results show that the resultant background DE calcification signal can be reduced. The root-mean-square of background DE calcification signal of 1962 μm with scatter-uncorrected data was reduced to 194 μm after scatter correction using the authors' algorithmic method. The range of background DE calcification signals using scatter-uncorrected data was reduced by 58% with scatter-corrected data by algorithmic method. With the scatter-correction algorithm and denoising, the minimum visible calcification size can be reduced from 380 to 280 μm.Conclusions: When applying the proposed algorithmic scatter correction to images, the resultant background DE calcification signals can be reduced and the CNR of calcifications can be improved. This method has similar or even better performance than pinhole-array interpolation method in scatter correction for DEDM; moreover, this method is convenient and requires no extra exposure to the patient. Although the proposed scatter correction method is effective, it is validated by a 5-cm-thick phantom with calcifications and homogeneous background. The method should be tested on structured backgrounds to more accurately gauge effectiveness.« less
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NASA Astrophysics Data System (ADS)
Shinzawa, Hideyuki; Mizukado, Junji
2018-03-01
Tensile deformations of a partially miscible blend of polymethyl methacrylate (PMMA) and polyethylene glycol (PEG) is studied by a rheo-optical characterization near-infrared (NIR) technique to probe deformation behavior during tensile deformation. Sets of NIR spectra of the polymer samples were collected by using an acousto-optic tunable filter (AOTF) NIR spectrometer coupled with a tensile testing machine as an excitation device. While deformations of the samples were readily captured as strain-dependent NIR spectra, the entire feature of the spectra was overwhelmed with the baseline fluctuation induced by the decrease in the sample thickness and subsequent change in the light scattering. Several pretreatment techniques, including multiplicative scatter collection (MSC) and null-space projection, are subjected to the NIR spectra prior to the determination of the sequential order of the spectral intensity changes by two-dimensional (2D) correlation analysis. The comparison of the MSC and null-space projection provided an interesting insight into the system, especially deformation-induced variation of light scattering observed during the tensile testing of the polymer sample. In addition, the sequential order determined with the 2D correlation spectra revealed that orientation of a specific part of PMMA chain occurs before that of the others because of the interaction between Cdbnd O group of PMMA and terminal sbnd OH group of PEG.
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NASA Astrophysics Data System (ADS)
Chen, Hua-cai; Chen, Xing-dan; Lu, Yong-jun; Cao, Zhi-qiang
2006-01-01
Near infrared (NIR) reflectance spectroscopy was used to develop a fast determination method for total ginsenosides in Ginseng (Panax Ginseng) powder. The spectra were analyzed with multiplicative signal correction (MSC) correlation method. The best correlative spectra region with the total ginsenosides content was 1660 nm~1880 nm and 2230nm~2380 nm. The NIR calibration models of ginsenosides were built with multiple linear regression (MLR), principle component regression (PCR) and partial least squares (PLS) regression respectively. The results showed that the calibration model built with PLS combined with MSC and the optimal spectrum region was the best one. The correlation coefficient and the root mean square error of correction validation (RMSEC) of the best calibration model were 0.98 and 0.15% respectively. The optimal spectrum region for calibration was 1204nm~2014nm. The result suggested that using NIR to rapidly determinate the total ginsenosides content in ginseng powder were feasible.
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Taylor, Amanda L; Murphree, Rendi; Ingram, L Amanda; Garman, Katie; Solomon, Deborah; Coffey, Eric; Walker, Deborah; Rogers, Marsha; Marder, Ellyn; Bottomley, Marie; Woron, Amy; Thomas, Linda; Roberts, Sheri; Hardin, Henrietta; Arjmandi, Parvin; Green, Alice; Simmons, Latoya; Cornell, Allyson; Dunn, John
2015-12-01
We describe multidrug-resistant (MDR) Salmonella Heidelberg infections associated with mechanically separated chicken (MSC) served at a county correctional facility. Twenty-three inmates met the case definition. All reported diarrhea, 19 (83%) reported fever, 16 (70%) reported vomiting, 4 (17%) had fever ≥103°F, and 3 (13%) were hospitalized. A case-control study found no single food item significantly associated with illness. Salmonella Heidelberg with an indistinguishable pulsed-field gel electrophoresis pattern was isolated from nine stool specimens; two isolates displayed resistance to a total of five drug classes, including the third-generation cephalosporin, ceftriaxone. MDR Salmonella Heidelberg might have contributed to the severity of illness. Salmonella Heidelberg indistinguishable from the outbreak subtype was isolated from unopened MSC. The environmental health assessment identified cross-contamination through poor food-handling practices as a possible contributing factor. Proper hand-washing techniques and safe food-handling practices were reviewed with the kitchen supervisor.
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Increased Mediterranean Magma Production and Volcanism Triggered by the Messinian Salinity Crisis
NASA Astrophysics Data System (ADS)
Sternai, P.; Caricchi, L.; Garcia-Castellanos, D.; Jolivet, L.; Sheldrake, T.; Castelltort, S.
2017-12-01
For more than four decades, large controversies about the causes, effects and timing of the Mediterranean Messinian Salinity Crisis (MSC) have evolved in the light of a continuously growing body of evidences. The igneous response to such extreme event, however, has remained largely unexplored despite known relationships between surface load variations and the production, transfer and eruption of magma. Here, we compile published geochemical data and recognize a two-fold increase of volcanic eruptions from pan-Mediterranean magmatic provinces coinciding with the proposed "shallow-water phase" of the MSC between 5.70-5.33 Ma. Estimates of surface load variations due to the desiccation event corrected for water density change and deposition of salt deposits suggest a net mean lithospheric unloading of up to 15 MPa during the shallow-water phase of the MSC. Because the timescale of interest is too short for changes of the Mediterranean tectonics to significantly affect the bulk of the magma production, we propose that such net surface unloading enhanced the mantle decompression melting and dike formation, in turn causing the observed increase of volcanic events. If correct, the Mediterranean magmatic record provides an independent validation of the "shallow-water" model for the formation of salt deposits and testifies the high sensitivity of the melting of the Earth's interior to the surface forcing.
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A study on scattering correction for γ-photon 3D imaging test method
NASA Astrophysics Data System (ADS)
Xiao, Hui; Zhao, Min; Liu, Jiantang; Chen, Hao
2018-03-01
A pair of 511KeV γ-photons is generated during a positron annihilation. Their directions differ by 180°. The moving path and energy information can be utilized to form the 3D imaging test method in industrial domain. However, the scattered γ-photons are the major factors influencing the imaging precision of the test method. This study proposes a γ-photon single scattering correction method from the perspective of spatial geometry. The method first determines possible scattering points when the scattered γ-photon pair hits the detector pair. The range of scattering angle can then be calculated according to the energy window. Finally, the number of scattered γ-photons denotes the attenuation of the total scattered γ-photons along its moving path. The corrected γ-photons are obtained by deducting the scattered γ-photons from the original ones. Two experiments are conducted to verify the effectiveness of the proposed scattering correction method. The results concluded that the proposed scattering correction method can efficiently correct scattered γ-photons and improve the test accuracy.
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Shidahara, Miho; Watabe, Hiroshi; Kim, Kyeong Min; Kato, Takashi; Kawatsu, Shoji; Kato, Rikio; Yoshimura, Kumiko; Iida, Hidehiro; Ito, Kengo
2005-10-01
An image-based scatter correction (IBSC) method was developed to convert scatter-uncorrected into scatter-corrected SPECT images. The purpose of this study was to validate this method by means of phantom simulations and human studies with 99mTc-labeled tracers, based on comparison with the conventional triple energy window (TEW) method. The IBSC method corrects scatter on the reconstructed image I(mub)AC with Chang's attenuation correction factor. The scatter component image is estimated by convolving I(mub)AC with a scatter function followed by multiplication with an image-based scatter fraction function. The IBSC method was evaluated with Monte Carlo simulations and 99mTc-ethyl cysteinate dimer SPECT human brain perfusion studies obtained from five volunteers. The image counts and contrast of the scatter-corrected images obtained by the IBSC and TEW methods were compared. Using data obtained from the simulations, the image counts and contrast of the scatter-corrected images obtained by the IBSC and TEW methods were found to be nearly identical for both gray and white matter. In human brain images, no significant differences in image contrast were observed between the IBSC and TEW methods. The IBSC method is a simple scatter correction technique feasible for use in clinical routine.
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Detection of oil spills using 13.3 GHz radar scatterometer
NASA Technical Reports Server (NTRS)
Krishen, K.
1972-01-01
The results of an analysis of 13.3-GHz single polarized scatterometer data collected during NASA/MSC Mission 135, flown on March 16, 1970 are reported. Data were gathered over a crude oil spill on the Gulf of Mexico off the Mississippi Delta. With the aid of RC-8 camera photographs, the scattering cross section was correlated with the extent of the oil spill. The scattering cross section at higher incidence angles decreased by 5 db to 10 db in the presence of the oil spill. This was attributed to oil's damping of small gravity and capillary waves. The composite scattering theory and the scatterometer acquired data were used to obtain an expression of radar scattering over ocean surfaces with oil spills. The study demonstrates that the presence and extent of oil spills can be detected using high frequency radar systems.
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Robust scatter correction method for cone-beam CT using an interlacing-slit plate
NASA Astrophysics Data System (ADS)
Huang, Kui-Dong; Xu, Zhe; Zhang, Ding-Hua; Zhang, Hua; Shi, Wen-Long
2016-06-01
Cone-beam computed tomography (CBCT) has been widely used in medical imaging and industrial nondestructive testing, but the presence of scattered radiation will cause significant reduction of image quality. In this article, a robust scatter correction method for CBCT using an interlacing-slit plate (ISP) is carried out for convenient practice. Firstly, a Gaussian filtering method is proposed to compensate the missing data of the inner scatter image, and simultaneously avoid too-large values of calculated inner scatter and smooth the inner scatter field. Secondly, an interlacing-slit scan without detector gain correction is carried out to enhance the practicality and convenience of the scatter correction method. Finally, a denoising step for scatter-corrected projection images is added in the process flow to control the noise amplification The experimental results show that the improved method can not only make the scatter correction more robust and convenient, but also achieve a good quality of scatter-corrected slice images. Supported by National Science and Technology Major Project of the Ministry of Industry and Information Technology of China (2012ZX04007021), Aeronautical Science Fund of China (2014ZE53059), and Fundamental Research Funds for Central Universities of China (3102014KYJD022)
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Stochastic Simulation Tool for Aerospace Structural Analysis
NASA Technical Reports Server (NTRS)
Knight, Norman F.; Moore, David F.
2006-01-01
Stochastic simulation refers to incorporating the effects of design tolerances and uncertainties into the design analysis model and then determining their influence on the design. A high-level evaluation of one such stochastic simulation tool, the MSC.Robust Design tool by MSC.Software Corporation, has been conducted. This stochastic simulation tool provides structural analysts with a tool to interrogate their structural design based on their mathematical description of the design problem using finite element analysis methods. This tool leverages the analyst's prior investment in finite element model development of a particular design. The original finite element model is treated as the baseline structural analysis model for the stochastic simulations that are to be performed. A Monte Carlo approach is used by MSC.Robust Design to determine the effects of scatter in design input variables on response output parameters. The tool was not designed to provide a probabilistic assessment, but to assist engineers in understanding cause and effect. It is driven by a graphical-user interface and retains the engineer-in-the-loop strategy for design evaluation and improvement. The application problem for the evaluation is chosen to be a two-dimensional shell finite element model of a Space Shuttle wing leading-edge panel under re-entry aerodynamic loading. MSC.Robust Design adds value to the analysis effort by rapidly being able to identify design input variables whose variability causes the most influence in response output parameters.
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Physics Model-Based Scatter Correction in Multi-Source Interior Computed Tomography.
Gong, Hao; Li, Bin; Jia, Xun; Cao, Guohua
2018-02-01
Multi-source interior computed tomography (CT) has a great potential to provide ultra-fast and organ-oriented imaging at low radiation dose. However, X-ray cross scattering from multiple simultaneously activated X-ray imaging chains compromises imaging quality. Previously, we published two hardware-based scatter correction methods for multi-source interior CT. Here, we propose a software-based scatter correction method, with the benefit of no need for hardware modifications. The new method is based on a physics model and an iterative framework. The physics model was derived analytically, and was used to calculate X-ray scattering signals in both forward direction and cross directions in multi-source interior CT. The physics model was integrated to an iterative scatter correction framework to reduce scatter artifacts. The method was applied to phantom data from both Monte Carlo simulations and physical experimentation that were designed to emulate the image acquisition in a multi-source interior CT architecture recently proposed by our team. The proposed scatter correction method reduced scatter artifacts significantly, even with only one iteration. Within a few iterations, the reconstructed images fast converged toward the "scatter-free" reference images. After applying the scatter correction method, the maximum CT number error at the region-of-interests (ROIs) was reduced to 46 HU in numerical phantom dataset and 48 HU in physical phantom dataset respectively, and the contrast-noise-ratio at those ROIs increased by up to 44.3% and up to 19.7%, respectively. The proposed physics model-based iterative scatter correction method could be useful for scatter correction in dual-source or multi-source CT.
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Correction of Altitude-Induced Changes in Performance of the Volumetric Diffusive Respirator
2017-04-05
to a plateau pressure. The positive pressure delivery of each percussive pulse is followed by a passive fall in pressure as the spring moves the ...AFRL-SA-WP-SR-2017-0007 Correction of Altitude- Induced Changes in Performance of the Volumetric Diffusive Respirator Thomas...Blakeman, MSc RRT April 2017 Air Force Research Laboratory 711th Human Performance Wing U.S. Air Force School of Aerospace
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Seebach, Caroline; Schultheiss, Judith; Wilhelm, Kerstin; Frank, Johannes; Henrich, Dirk
2010-07-01
Various synthetic bone-graft substitutes are used commercially as osteoconductive scaffolds in the treatment of bone defects and fractures. The role of bone-graft substitutes is changing from osteoconductive conduits for growth to an delivery system for biologic fracture treatments. Achieving optimal bone regeneration requires biologics (e.g. MSC) and using the correct scaffold incorporated into a local environment for bone regeneration. The need for an unlimited supply with high quality bone-graft substitutes continue to find alternatives for bone replacement surgery. This in vitro study investigates cell seeding efficiency, metabolism, gene expression and growth behaviour of MSC sown on six commercially clinical available bone-graft substitutes in order to define their biological properties: synthetic silicate-substituted porous hydroxyapatite (Actifuse ABX), synthetic alpha-TCP (Biobase), synthetic beta-TCP (Vitoss), synthetic beta-TCP (Chronos), processed human cancellous allograft (Tutoplast) and processed bovines hydroxyapatite ceramic (Cerabone). 250,000 MSC derived from human bone marrow (n=4) were seeded onto the scaffolds, respectively. On days 2, 6 and 10 the adherence of MSC (fluorescence microscopy) and cellular activity (MTT assay) were analysed. Osteogenic gene expression (cbfa-1) was analysed by RT-PCR and scanning electron microscopy was performed. The highest number of adhering cells was found on Tutoplast (e.g. day 6: 110.0+/-24.0 cells/microscopic field; p<0.05) followed by Chronos (47.5+/-19.5, p<0.05), Actifuse ABX (19.1+/-4.4), Biobase (15.7+/-9.9), Vitoss (8.8+/-8.7) and Cerabone (8.1+/-2.2). MSC seeded onto Tutoplast showed highest metabolic activity and gene expression of cbfa-1. These data are confirmed by scanning electron microscopy. The cell shapes varied from round-shaped cells to wide spread cells and cell clusters, depending on the bone-graft substitutes. Processed human cancellous allograft is a well-structured and biocompatible scaffold for ingrowing MSC in vitro. Of all other synthetical scaffolds, beta-tricalcium phosphate (Chronos) have shown the best growth behaviour for MSC. Our results indicate that various bone-graft substitutes influence cell seeding efficiency, metabolic activity and growth behaviour of MSC in different manners. We detected a high variety of cellular integration of MSC in vitro, which may be important for bony integration in the clinical setting. 2010 Elsevier Ltd. All rights reserved.
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Investigation on Beam-Blocker-Based Scatter Correction Method for Improving CT Number Accuracy
NASA Astrophysics Data System (ADS)
Lee, Hoyeon; Min, Jonghwan; Lee, Taewon; Pua, Rizza; Sabir, Sohail; Yoon, Kown-Ha; Kim, Hokyung; Cho, Seungryong
2017-03-01
Cone-beam computed tomography (CBCT) is gaining widespread use in various medical and industrial applications but suffers from substantially larger amount of scatter than that in the conventional diagnostic CT resulting in relatively poor image quality. Various methods that can reduce and/or correct for the scatter in the CBCT have therefore been developed. Scatter correction method that uses a beam-blocker has been considered a direct measurement-based approach providing accurate scatter estimation from the data in the shadows of the beam-blocker. To the best of our knowledge, there has been no record reporting the significance of the scatter from the beam-blocker itself in such correction methods. In this paper, we identified the scatter from the beam-blocker that is detected in the object-free projection data investigated its influence on the image accuracy of CBCT reconstructed images, and developed a scatter correction scheme that takes care of this scatter as well as the scatter from the scanned object.
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Detection of oil spills using a 13.3-GHz radar scatterometer.
NASA Technical Reports Server (NTRS)
Krishen, K.
1973-01-01
This paper describes the results of an analysis of 13.3-GHz single-polarized scatterometer data collected during NASA/MSC mission 135, flown on March 16, 1970. Data were gathered over a crude oil spill on the Gulf of Mexico (test site 128) off the Mississippi delta. With the aid of RC-8 camera photographs the scattering cross section was correlated with the extent of the oil spill. The scattering cross section at higher incidence angles (25 to 50 deg) decreased by 5-10 db in the presence of the oil spill. This was attributed to the damping by oil of small gravity and capillary waves. The composite scattering theory and the scatterometer-acquired data were used to obtain an expression of radar scattering over ocean surfaces with oil spills. The study demonstrates that the presence and extent of oil spills can be detected with high-frequency radar systems.
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Marques Junior, Jucelino Medeiros; Muller, Aline Lima Hermes; Foletto, Edson Luiz; da Costa, Adilson Ben; Bizzi, Cezar Augusto; Irineu Muller, Edson
2015-01-01
A method for determination of propranolol hydrochloride in pharmaceutical preparation using near infrared spectrometry with fiber optic probe (FTNIR/PROBE) and combined with chemometric methods was developed. Calibration models were developed using two variable selection models: interval partial least squares (iPLS) and synergy interval partial least squares (siPLS). The treatments based on the mean centered data and multiplicative scatter correction (MSC) were selected for models construction. A root mean square error of prediction (RMSEP) of 8.2 mg g(-1) was achieved using siPLS (s2i20PLS) algorithm with spectra divided into 20 intervals and combination of 2 intervals (8501 to 8801 and 5201 to 5501 cm(-1)). Results obtained by the proposed method were compared with those using the pharmacopoeia reference method and significant difference was not observed. Therefore, proposed method allowed a fast, precise, and accurate determination of propranolol hydrochloride in pharmaceutical preparations. Furthermore, it is possible to carry out on-line analysis of this active principle in pharmaceutical formulations with use of fiber optic probe.
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Tahir, Haroon Elrasheid; Xiaobo, Zou; Zhihua, Li; Jiyong, Shi; Zhai, Xiaodong; Wang, Sheng; Mariod, Abdalbasit Adam
2017-07-01
Fourier transform infrared with attenuated total reflectance (FTIR-ATR) and Raman spectroscopy combined with partial least square regression (PLSR) were applied for the prediction of phenolic compounds and antioxidant activity in honey. Standards of catechin, syringic, vanillic, and chlorogenic acids were used for the identification and quantification of the individual phenolic compounds in six honey varieties using HPLC-DAD. Total antioxidant activity (TAC) and ferrous chelating capacity were measured spectrophotometrically. For the establishment of PLSR model, Raman spectra with Savitzky-Golay smoothing in wavenumber region 1500-400cm -1 was used while for FTIR-ATR the wavenumber regions of 1800-700 and 3000-2800cm -1 with multiplicative scattering correction (MSC) and Savitzky-Golay smoothing were used. The determination coefficients (R 2 ) were ranged from 0.9272 to 0.9992 for Raman while from 0.9461 to 0.9988 for FTIT-ART. The FTIR-ATR and Raman demonstrated to be simple, rapid and nondestructive methods to quantify phenolic compounds and antioxidant activities in honey. Copyright © 2017 Elsevier Ltd. All rights reserved.
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NASA Astrophysics Data System (ADS)
Scafetta, Nicola
2018-07-01
Holm (ASR, 2018) claims that Scafetta (ASR 57, 2121-2135, 2016) is "irreproducible" because I would have left "undocumented" the values of two parameters (a reduced-rank index p and a regularization term δ) that he claimed to be requested in the Magnitude Squared Coherence Canonical Correlation Analysis (MSC-CCA). Yet, my analysis did not require such two parameters. In fact: (1) using the MSC-CCA reduced-rank option neither changes the result nor was needed since Scafetta (2016) statistically evaluated the significance of the coherence spectral peaks; (2) the analysis algorithm neither contains nor needed the regularization term δ . Herein I show that Holm could not replicate Scafetta (2016) because he used different analysis algorithms. In fact, although Holm claimed to be using MSC-CCA, for his Figs. 2-4 he used a MatLab code labeled "gcs_cca_1D.m" (see paragraph 2 of his Section 3), which Holm also modified, that implements a different methodology known as the Generalized Coherence Spectrum using the Canonical Correlation Analysis (GCS-CCA). This code is herein demonstrated to be unreliable under specific statistical circumstances such as those required to replicate Scafetta (2016). On the contrary, the MSC-CCA method is stable and reliable. Moreover, Holm could not replicate my result also in his Fig. 5 because there he used the basic Welch MSC algorithm by erroneously equating it to MSC-CCA. Herein I clarify step-by-step how to proceed with the correct analysis, and I fully confirm the 95% significance of my results. I add data and codes to easily replicate my results.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Winkler, Sandra, E-mail: sandra.pelz@medizin.uni-leipzig.de; Borkham-Kamphorst, Erawan, E-mail: ekamphorst@ukaachen.de; Stock, Peggy, E-mail: peggy.stock@medizin.uni-leipzig.de
Non-alcoholic steatohepatitis (NASH) is a frequent clinical picture characterised by hepatic inflammation, lipid accumulation and fibrosis. When untreated, NASH bears a high risk of developing liver cirrhosis and consecutive hepatocellular carcinoma requiring liver transplantation in its end-stage. However, donor organ scarcity has prompted the search for alternatives, of which hepatocyte or stem cell-derived hepatocyte transplantation are regarded auspicious options of treatment. Mesenchymal stem cells (MSC) are able to differentiate into hepatocyte-like cells and thus may represent an alternative cell source to primary hepatocytes. In addition these cells feature anti-inflammatory and pro-regenerative characteristics, which might favour liver recovery from NASH. Themore » aim of this study was to investigate the potential benefit of hepatocyte-like cells derived from human bone marrow MSC in a mouse model of diet-induced NASH. Seven days post-transplant, human hepatocyte-like cells were found in the mouse liver parenchyma. Triglyceride depositions were lowered in the liver but restored to normal in the blood. Hepatic inflammation was attenuated as verified by decreased expression of the acute phase protein serum amyloid A, inflammation-associated markers (e.g. lipocalin 2), as well as the pro-inflammatory cytokine TNFα. Moreover, the proliferation of host hepatocytes that indicate the regenerative capacity in livers receiving cell transplants was enhanced. Transplantation of MSC-derived human hepatocyte-like cells corrects NASH in mice by restoring triglyceride depositions, reducing inflammation and augmenting the regenerative capacity of the liver. - Highlights: • First time to show NASH in an immune-deficient mouse model. • Human MSC attenuate NASH and improve lipid homeostasis. • MSC act anti-fibrotic and augment liver regeneration by stimulation of proliferation. • Pre-clinical assessment of human MSC for stem cell-based therapy of NASH.« less
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Teuho, Jarmo; Saunavaara, Virva; Tolvanen, Tuula; Tuokkola, Terhi; Karlsson, Antti; Tuisku, Jouni; Teräs, Mika
2017-10-01
In PET, corrections for photon scatter and attenuation are essential for visual and quantitative consistency. MR attenuation correction (MRAC) is generally conducted by image segmentation and assignment of discrete attenuation coefficients, which offer limited accuracy compared with CT attenuation correction. Potential inaccuracies in MRAC may affect scatter correction, because the attenuation image (μ-map) is used in single scatter simulation (SSS) to calculate the scatter estimate. We assessed the impact of MRAC to scatter correction using 2 scatter-correction techniques and 3 μ-maps for MRAC. Methods: The tail-fitted SSS (TF-SSS) and a Monte Carlo-based single scatter simulation (MC-SSS) algorithm implementations on the Philips Ingenuity TF PET/MR were used with 1 CT-based and 2 MR-based μ-maps. Data from 7 subjects were used in the clinical evaluation, and a phantom study using an anatomic brain phantom was conducted. Scatter-correction sinograms were evaluated for each scatter correction method and μ-map. Absolute image quantification was investigated with the phantom data. Quantitative assessment of PET images was performed by volume-of-interest and ratio image analysis. Results: MRAC did not result in large differences in scatter algorithm performance, especially with TF-SSS. Scatter sinograms and scatter fractions did not reveal large differences regardless of the μ-map used. TF-SSS showed slightly higher absolute quantification. The differences in volume-of-interest analysis between TF-SSS and MC-SSS were 3% at maximum in the phantom and 4% in the patient study. Both algorithms showed excellent correlation with each other with no visual differences between PET images. MC-SSS showed a slight dependency on the μ-map used, with a difference of 2% on average and 4% at maximum when a μ-map without bone was used. Conclusion: The effect of different MR-based μ-maps on the performance of scatter correction was minimal in non-time-of-flight 18 F-FDG PET/MR brain imaging. The SSS algorithm was not affected significantly by MRAC. The performance of the MC-SSS algorithm is comparable but not superior to TF-SSS, warranting further investigations of algorithm optimization and performance with different radiotracers and time-of-flight imaging. © 2017 by the Society of Nuclear Medicine and Molecular Imaging.
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The beam stop array method to measure object scatter in digital breast tomosynthesis
NASA Astrophysics Data System (ADS)
Lee, Haeng-hwa; Kim, Ye-seul; Park, Hye-Suk; Kim, Hee-Joung; Choi, Jae-Gu; Choi, Young-Wook
2014-03-01
Scattered radiation is inevitably generated in the object. The distribution of the scattered radiation is influenced by object thickness, filed size, object-to-detector distance, and primary energy. One of the investigations to measure scatter intensities involves measuring the signal detected under the shadow of the lead discs of a beam-stop array (BSA). The measured scatter by BSA includes not only the scattered radiation within the object (object scatter), but also the external scatter source. The components of external scatter source include the X-ray tube, detector, collimator, x-ray filter, and BSA. Excluding background scattered radiation can be applied to different scanner geometry by simple parameter adjustments without prior knowledge of the scanned object. In this study, a method using BSA to differentiate scatter in phantom (object scatter) from external background was used. Furthermore, this method was applied to BSA algorithm to correct the object scatter. In order to confirm background scattered radiation, we obtained the scatter profiles and scatter fraction (SF) profiles in the directions perpendicular to the chest wall edge (CWE) with and without scattering material. The scatter profiles with and without the scattering material were similar in the region between 127 mm and 228 mm from chest wall. This result indicated that the measured scatter by BSA included background scatter. Moreover, the BSA algorithm with the proposed method could correct the object scatter because the total radiation profiles of object scatter correction corresponded to original image in the region between 127 mm and 228 mm from chest wall. As a result, the BSA method to measure object scatter could be used to remove background scatter. This method could apply for different scanner geometry after background scatter correction. In conclusion, the BSA algorithm with the proposed method is effective to correct object scatter.
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NASA Astrophysics Data System (ADS)
Ye, Huping; Li, Junsheng; Zhu, Jianhua; Shen, Qian; Li, Tongji; Zhang, Fangfang; Yue, Huanyin; Zhang, Bing; Liao, Xiaohan
2017-10-01
The absorption coefficient of water is an important bio-optical parameter for water optics and water color remote sensing. However, scattering correction is essential to obtain accurate absorption coefficient values in situ using the nine-wavelength absorption and attenuation meter AC9. Establishing the correction always fails in Case 2 water when the correction assumes zero absorption in the near-infrared (NIR) region and underestimates the absorption coefficient in the red region, which affect processes such as semi-analytical remote sensing inversion. In this study, the scattering contribution was evaluated by an exponential fitting approach using AC9 measurements at seven wavelengths (412, 440, 488, 510, 532, 555, and 715 nm) and by applying scattering correction. The correction was applied to representative in situ data of moderately turbid coastal water, highly turbid coastal water, eutrophic inland water, and turbid inland water. The results suggest that the absorption levels in the red and NIR regions are significantly higher than those obtained using standard scattering error correction procedures. Knowledge of the deviation between this method and the commonly used scattering correction methods will facilitate the evaluation of the effect on satellite remote sensing of water constituents and general optical research using different scattering-correction methods.
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Impact of reconstruction parameters on quantitative I-131 SPECT
NASA Astrophysics Data System (ADS)
van Gils, C. A. J.; Beijst, C.; van Rooij, R.; de Jong, H. W. A. M.
2016-07-01
Radioiodine therapy using I-131 is widely used for treatment of thyroid disease or neuroendocrine tumors. Monitoring treatment by accurate dosimetry requires quantitative imaging. The high energy photons however render quantitative SPECT reconstruction challenging, potentially requiring accurate correction for scatter and collimator effects. The goal of this work is to assess the effectiveness of various correction methods on these effects using phantom studies. A SPECT/CT acquisition of the NEMA IEC body phantom was performed. Images were reconstructed using the following parameters: (1) without scatter correction, (2) with triple energy window (TEW) scatter correction and (3) with Monte Carlo-based scatter correction. For modelling the collimator-detector response (CDR), both (a) geometric Gaussian CDRs as well as (b) Monte Carlo simulated CDRs were compared. Quantitative accuracy, contrast to noise ratios and recovery coefficients were calculated, as well as the background variability and the residual count error in the lung insert. The Monte Carlo scatter corrected reconstruction method was shown to be intrinsically quantitative, requiring no experimentally acquired calibration factor. It resulted in a more accurate quantification of the background compartment activity density compared with TEW or no scatter correction. The quantification error relative to a dose calibrator derived measurement was found to be <1%,-26% and 33%, respectively. The adverse effects of partial volume were significantly smaller with the Monte Carlo simulated CDR correction compared with geometric Gaussian or no CDR modelling. Scatter correction showed a small effect on quantification of small volumes. When using a weighting factor, TEW correction was comparable to Monte Carlo reconstruction in all measured parameters, although this approach is clinically impractical since this factor may be patient dependent. Monte Carlo based scatter correction including accurately simulated CDR modelling is the most robust and reliable method to reconstruct accurate quantitative iodine-131 SPECT images.
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Evaluation of simulation-based scatter correction for 3-D PET cardiac imaging
NASA Astrophysics Data System (ADS)
Watson, C. C.; Newport, D.; Casey, M. E.; deKemp, R. A.; Beanlands, R. S.; Schmand, M.
1997-02-01
Quantitative imaging of the human thorax poses one of the most difficult challenges for three-dimensional (3-D) (septaless) positron emission tomography (PET), due to the strong attenuation of the annihilation radiation and the large contribution of scattered photons to the data. In [/sup 18/F] fluorodeoxyglucose (FDG) studies of the heart with the patient's arms in the field of view, the contribution of scattered events can exceed 50% of the total detected coincidences. Accurate correction for this scatter component is necessary for meaningful quantitative image analysis and tracer kinetic modeling. For this reason, the authors have implemented a single-scatter simulation technique for scatter correction in positron volume imaging. Here, they describe this algorithm and present scatter correction results from human and chest phantom studies.
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Meng, Bowen; Lee, Ho; Xing, Lei; Fahimian, Benjamin P.
2013-01-01
Purpose: X-ray scatter results in a significant degradation of image quality in computed tomography (CT), representing a major limitation in cone-beam CT (CBCT) and large field-of-view diagnostic scanners. In this work, a novel scatter estimation and correction technique is proposed that utilizes peripheral detection of scatter during the patient scan to simultaneously acquire image and patient-specific scatter information in a single scan, and in conjunction with a proposed compressed sensing scatter recovery technique to reconstruct and correct for the patient-specific scatter in the projection space. Methods: The method consists of the detection of patient scatter at the edges of the field of view (FOV) followed by measurement based compressed sensing recovery of the scatter through-out the projection space. In the prototype implementation, the kV x-ray source of the Varian TrueBeam OBI system was blocked at the edges of the projection FOV, and the image detector in the corresponding blocked region was used for scatter detection. The design enables image data acquisition of the projection data on the unblocked central region of and scatter data at the blocked boundary regions. For the initial scatter estimation on the central FOV, a prior consisting of a hybrid scatter model that combines the scatter interpolation method and scatter convolution model is estimated using the acquired scatter distribution on boundary region. With the hybrid scatter estimation model, compressed sensing optimization is performed to generate the scatter map by penalizing the L1 norm of the discrete cosine transform of scatter signal. The estimated scatter is subtracted from the projection data by soft-tuning, and the scatter-corrected CBCT volume is obtained by the conventional Feldkamp-Davis-Kress algorithm. Experimental studies using image quality and anthropomorphic phantoms on a Varian TrueBeam system were carried out to evaluate the performance of the proposed scheme. Results: The scatter shading artifacts were markedly suppressed in the reconstructed images using the proposed method. On the Catphan©504 phantom, the proposed method reduced the error of CT number to 13 Hounsfield units, 10% of that without scatter correction, and increased the image contrast by a factor of 2 in high-contrast regions. On the anthropomorphic phantom, the spatial nonuniformity decreased from 10.8% to 6.8% after correction. Conclusions: A novel scatter correction method, enabling unobstructed acquisition of the high frequency image data and concurrent detection of the patient-specific low frequency scatter data at the edges of the FOV, is proposed and validated in this work. Relative to blocker based techniques, rather than obstructing the central portion of the FOV which degrades and limits the image reconstruction, compressed sensing is used to solve for the scatter from detection of scatter at the periphery of the FOV, enabling for the highest quality reconstruction in the central region and robust patient-specific scatter correction. PMID:23298098
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Federal Register 2010, 2011, 2012, 2013, 2014
2012-10-26
... Inventory Completion: Maxwell Museum of Anthropology, University of New Mexico, Albuquerque, NM; Correction... affiliated with the human remains may contact the Maxwell Museum of Anthropology. Repatriation of the human..., Maxwell Museum of Anthropology, MSC01 1050, University of New Mexico, Albuquerque, NM 87131-0001...
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D'estanque, Emmanuel; Hedon, Christophe; Lattuca, Benoît; Bourdon, Aurélie; Benkiran, Meriem; Verd, Aurélie; Roubille, François; Mariano-Goulart, Denis
2017-08-01
Dual-isotope 201 Tl/ 123 I-MIBG SPECT can assess trigger zones (dysfunctions in the autonomic nervous system located in areas of viable myocardium) that are substrate for ventricular arrhythmias after STEMI. This study evaluated the necessity of delayed acquisition and scatter correction for dual-isotope 201 Tl/ 123 I-MIBG SPECT studies with a CZT camera to identify trigger zones after revascularization in patients with STEMI in routine clinical settings. Sixty-nine patients were prospectively enrolled after revascularization to undergo 201 Tl/ 123 I-MIBG SPECT using a CZT camera (Discovery NM 530c, GE). The first acquisition was a single thallium study (before MIBG administration); the second and the third were early and late dual-isotope studies. We compared the scatter-uncorrected and scatter-corrected (TEW method) thallium studies with the results of magnetic resonance imaging or transthoracic echography (reference standard) to diagnose myocardial necrosis. Summed rest scores (SRS) were significantly higher in the delayed MIBG studies than the early MIBG studies. SRS and necrosis surface were significantly higher in the delayed thallium studies with scatter correction than without scatter correction, leading to less trigger zone diagnosis for the scatter-corrected studies. Compared with the scatter-uncorrected studies, the late thallium scatter-corrected studies provided the best diagnostic values for myocardial necrosis assessment. Delayed acquisitions and scatter-corrected dual-isotope 201 Tl/ 123 I-MIBG SPECT acquisitions provide an improved evaluation of trigger zones in routine clinical settings after revascularization for STEMI.
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A single-scattering correction for the seismo-acoustic parabolic equation.
Collins, Michael D
2012-04-01
An efficient single-scattering correction that does not require iterations is derived and tested for the seismo-acoustic parabolic equation. The approach is applicable to problems involving gradual range dependence in a waveguide with fluid and solid layers, including the key case of a sloping fluid-solid interface. The single-scattering correction is asymptotically equivalent to a special case of a single-scattering correction for problems that only have solid layers [Küsel et al., J. Acoust. Soc. Am. 121, 808-813 (2007)]. The single-scattering correction has a simple interpretation (conservation of interface conditions in an average sense) that facilitated its generalization to problems involving fluid layers. Promising results are obtained for problems in which the ocean bottom interface has a small slope.
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Brunner, Stephen; Nett, Brian E; Tolakanahalli, Ranjini; Chen, Guang-Hong
2011-02-21
X-ray scatter is a significant problem in cone-beam computed tomography when thicker objects and larger cone angles are used, as scattered radiation can lead to reduced contrast and CT number inaccuracy. Advances have been made in x-ray computed tomography (CT) by incorporating a high quality prior image into the image reconstruction process. In this paper, we extend this idea to correct scatter-induced shading artifacts in cone-beam CT image-guided radiation therapy. Specifically, this paper presents a new scatter correction algorithm which uses a prior image with low scatter artifacts to reduce shading artifacts in cone-beam CT images acquired under conditions of high scatter. The proposed correction algorithm begins with an empirical hypothesis that the target image can be written as a weighted summation of a series of basis images that are generated by raising the raw cone-beam projection data to different powers, and then, reconstructing using the standard filtered backprojection algorithm. The weight for each basis image is calculated by minimizing the difference between the target image and the prior image. The performance of the scatter correction algorithm is qualitatively and quantitatively evaluated through phantom studies using a Varian 2100 EX System with an on-board imager. Results show that the proposed scatter correction algorithm using a prior image with low scatter artifacts can substantially mitigate scatter-induced shading artifacts in both full-fan and half-fan modes.
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Theory and Application of Photoelectron Diffraction for Complex Oxide Systems
NASA Astrophysics Data System (ADS)
Chassé, Angelika; Chassé, Thomas
2018-06-01
X-ray photoelectron diffraction (XPD) has been used to investigate film structures and local sites of surface and dopant atoms in complex oxide materials. We have performed angular-resolved measurements of intensity distribution curves (ADCs) and patterns (ADPs) of elemental core level intensities from binary to quaternary mixed oxide samples and compared them to multiple-scattering cluster (MSC) calculations in order to derive information on structural models and related parameters. MSC calculations permitted to describe both bulk diffraction features of binary oxide MnO(001) and the thickness-dependence of the tetragonal distortion of epitaxial MnO films on Ag(001). XPD was further used to investigate the surface termination of perovskite SrTiO3 and BaTiO3 substrates in order to evaluate influence of different ex situ and in situ preparation procedures on the surface layers, which are crucial for quality of following film growth. Despite the similarity of local environments of Sr (Ba) and Ti atoms in the perovskite film structure an angular region in the ADCs was identified as a fingerprint with the help of MSC simulations which provided clear conclusions on the perovskite oxide surfaces. Dopant sites in quaternary perovskite manganites La1-xCaxMnO3, La1-xSrxMnO3, and La1-xCexMnO3 were studied with polar angle scans of the photoemission intensities of host and dopant atoms. Both direct comparison of experimental ADCs and to the simulations within MSC models confirm the occupation of A sites by the dopants and the structural quality of the complex oxide films.
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Sunwoo, Mun Kyung; Yun, Hyuk Jin; Song, Sook K.; Ham, Ji Hyun; Hong, Jin Yong; Lee, Ji E.; Lee, Hye S.; Sohn, Young H.; Lee, Jong-Min; Lee, Phil Hyu
2014-01-01
Multiple system atrophy (MSA) is an adult-onset, sporadic neurodegenerative disease. Because the prognosis of MSA is fatal, neuroprotective or regenerative strategies may be invaluable in MSA treatment. Previously, we obtained clinical and imaging evidence that mesenchymal stem cell (MSC) treatment could have a neuroprotective role in MSA patients. In the present study, we evaluated the effects of MSC therapy on longitudinal changes in subcortical deep gray matter volumes and cortical thickness and their association with cognitive performance. Clinical and imaging data were obtained from our previous randomized trial of autologous MSC in MSA patients. During 1-year follow-up, we assessed longitudinal differences in automatic segmentation-based subcortical deep gray matter volumes and vertex-wise cortical thickness between placebo (n = 15) and MSC groups (n = 11). Next, we performed correlation analysis between the changes in cortical thickness and changes in the Korean version of the Montreal Cognitive Assessment (MoCA) scores and cognitive performance of each cognitive subdomain using a multiple, comparison correction. There were no significant differences in age at baseline, age at disease onset, gender ratio, disease duration, clinical severity, MoCA score, or education level between the groups. The automated subcortical volumetric analysis revealed that the changes in subcortical deep gray matter volumes of the caudate, putamen, and thalamus did not differ significantly between the groups. The areas of cortical thinning over time in the placebo group were more extensive, including the frontal, temporal, and parietal areas, whereas these areas in the MSC group were less extensive. Correlation analysis indicated that declines in MoCA scores and phonemic fluency during the follow-up period were significantly correlated with cortical thinning of the frontal and posterior temporal areas and anterior temporal areas in MSA patients, respectively. In contrast, no significant correlations were observed in the MSC group. These results suggest that MSC treatment in patients with MSA may modulate cortical thinning over time and related cognitive performance, inferring a future therapeutic candidate for cognitive disorders. PMID:24982631
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Kossobokov, V.G.; Romashkova, L.L.; Keilis-Borok, V. I.; Healy, J.H.
1999-01-01
Algorithms M8 and MSc (i.e., the Mendocino Scenario) were used in a real-time intermediate-term research prediction of the strongest earthquakes in the Circum-Pacific seismic belt. Predictions are made by M8 first. Then, the areas of alarm are reduced by MSc at the cost that some earthquakes are missed in the second approximation of prediction. In 1992-1997, five earthquakes of magnitude 8 and above occurred in the test area: all of them were predicted by M8 and MSc identified correctly the locations of four of them. The space-time volume of the alarms is 36% and 18%, correspondingly, when estimated with a normalized product measure of empirical distribution of epicenters and uniform time. The statistical significance of the achieved results is beyond 99% both for M8 and MSc. For magnitude 7.5 + , 10 out of 19 earthquakes were predicted by M8 in 40% and five were predicted by M8-MSc in 13% of the total volume considered. This implies a significance level of 81% for M8 and 92% for M8-MSc. The lower significance levels might result from a global change in seismic regime in 1993-1996, when the rate of the largest events has doubled and all of them become exclusively normal or reversed faults. The predictions are fully reproducible; the algorithms M8 and MSc in complete formal definitions were published before we started our experiment [Keilis-Borok, V.I., Kossobokov, V.G., 1990. Premonitory activation of seismic flow: Algorithm M8, Phys. Earth and Planet. Inter. 61, 73-83; Kossobokov, V.G., Keilis-Borok, V.I., Smith, S.W., 1990. Localization of intermediate-term earthquake prediction, J. Geophys. Res., 95, 19763-19772; Healy, J.H., Kossobokov, V.G., Dewey, J.W., 1992. A test to evaluate the earthquake prediction algorithm, M8. U.S. Geol. Surv. OFR 92-401]. M8 is available from the IASPEI Software Library [Healy, J.H., Keilis-Borok, V.I., Lee, W.H.K. (Eds.), 1997. Algorithms for Earthquake Statistics and Prediction, Vol. 6. IASPEI Software Library]. ?? 1999 Elsevier Science B.V. All rights reserved.
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[Gaussian process regression and its application in near-infrared spectroscopy analysis].
Feng, Ai-Ming; Fang, Li-Min; Lin, Min
2011-06-01
Gaussian process (GP) is applied in the present paper as a chemometric method to explore the complicated relationship between the near infrared (NIR) spectra and ingredients. After the outliers were detected by Monte Carlo cross validation (MCCV) method and removed from dataset, different preprocessing methods, such as multiplicative scatter correction (MSC), smoothing and derivate, were tried for the best performance of the models. Furthermore, uninformative variable elimination (UVE) was introduced as a variable selection technique and the characteristic wavelengths obtained were further employed as input for modeling. A public dataset with 80 NIR spectra of corn was introduced as an example for evaluating the new algorithm. The optimal models for oil, starch and protein were obtained by the GP regression method. The performance of the final models were evaluated according to the root mean square error of calibration (RMSEC), root mean square error of cross-validation (RMSECV), root mean square error of prediction (RMSEP) and correlation coefficient (r). The models give good calibration ability with r values above 0.99 and the prediction ability is also satisfactory with r values higher than 0.96. The overall results demonstrate that GP algorithm is an effective chemometric method and is promising for the NIR analysis.
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NASA Astrophysics Data System (ADS)
Müller, Aline Lima Hermes; Picoloto, Rochele Sogari; Mello, Paola de Azevedo; Ferrão, Marco Flores; dos Santos, Maria de Fátima Pereira; Guimarães, Regina Célia Lourenço; Müller, Edson Irineu; Flores, Erico Marlon Moraes
2012-04-01
Total sulfur concentration was determined in atmospheric residue (AR) and vacuum residue (VR) samples obtained from petroleum distillation process by Fourier transform infrared spectroscopy with attenuated total reflectance (FT-IR/ATR) in association with chemometric methods. Calibration and prediction set consisted of 40 and 20 samples, respectively. Calibration models were developed using two variable selection models: interval partial least squares (iPLS) and synergy interval partial least squares (siPLS). Different treatments and pre-processing steps were also evaluated for the development of models. The pre-treatment based on multiplicative scatter correction (MSC) and the mean centered data were selected for models construction. The use of siPLS as variable selection method provided a model with root mean square error of prediction (RMSEP) values significantly better than those obtained by PLS model using all variables. The best model was obtained using siPLS algorithm with spectra divided in 20 intervals and combinations of 3 intervals (911-824, 823-736 and 737-650 cm-1). This model produced a RMSECV of 400 mg kg-1 S and RMSEP of 420 mg kg-1 S, showing a correlation coefficient of 0.990.
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NASA Astrophysics Data System (ADS)
Xie, Shi-Peng; Luo, Li-Min
2012-06-01
The authors propose a combined scatter reduction and correction method to improve image quality in cone beam computed tomography (CBCT). The scatter kernel superposition (SKS) method has been used occasionally in previous studies. However, this method differs in that a scatter detecting blocker (SDB) was used between the X-ray source and the tested object to model the self-adaptive scatter kernel. This study first evaluates the scatter kernel parameters using the SDB, and then isolates the scatter distribution based on the SKS. The quality of image can be improved by removing the scatter distribution. The results show that the method can effectively reduce the scatter artifacts, and increase the image quality. Our approach increases the image contrast and reduces the magnitude of cupping. The accuracy of the SKS technique can be significantly improved in our method by using a self-adaptive scatter kernel. This method is computationally efficient, easy to implement, and provides scatter correction using a single scan acquisition.
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Optimization-based scatter estimation using primary modulation for computed tomography
DOE Office of Scientific and Technical Information (OSTI.GOV)
Chen, Yi; Ma, Jingchen; Zhao, Jun, E-mail: junzhao
Purpose: Scatter reduces the image quality in computed tomography (CT), but scatter correction remains a challenge. A previously proposed primary modulation method simultaneously obtains the primary and scatter in a single scan. However, separating the scatter and primary in primary modulation is challenging because it is an underdetermined problem. In this study, an optimization-based scatter estimation (OSE) algorithm is proposed to estimate and correct scatter. Methods: In the concept of primary modulation, the primary is modulated, but the scatter remains smooth by inserting a modulator between the x-ray source and the object. In the proposed algorithm, an objective function ismore » designed for separating the scatter and primary. Prior knowledge is incorporated in the optimization-based framework to improve the accuracy of the estimation: (1) the primary is always positive; (2) the primary is locally smooth and the scatter is smooth; (3) the location of penumbra can be determined; and (4) the scatter-contaminated data provide knowledge about which part is smooth. Results: The simulation study shows that the edge-preserving weighting in OSE improves the estimation accuracy near the object boundary. Simulation study also demonstrates that OSE outperforms the two existing primary modulation algorithms for most regions of interest in terms of the CT number accuracy and noise. The proposed method was tested on a clinical cone beam CT, demonstrating that OSE corrects the scatter even when the modulator is not accurately registered. Conclusions: The proposed OSE algorithm improves the robustness and accuracy in scatter estimation and correction. This method is promising for scatter correction of various kinds of x-ray imaging modalities, such as x-ray radiography, cone beam CT, and the fourth-generation CT.« less
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2011-10-01
mail: gaelle.casagrande@dga.defense.gouv.fr). Y. Stephan is with the Service Hydrographique et Oceanographique de la Marine (SHOM), Brest 29200...the two first modes of the EOF analysis. In black, original data temperature profiles. The profiles are located on the expansion coefficient scatter...in 2000, the M.Sc. degree in oceanography, £ H meteorology, and environment from the University de Jussieu, Paris , France, in 2002, and the
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Gearhart, A; Peterson, T; Johnson, L
2015-06-15
Purpose: To evaluate the impact of the exceptional energy resolution of germanium detectors for preclinical SPECT in comparison to conventional detectors. Methods: A cylindrical water phantom was created in GATE with a spherical Tc-99m source in the center. Sixty-four projections over 360 degrees using a pinhole collimator were simulated. The same phantom was simulated using air instead of water to establish the true reconstructed voxel intensity without attenuation. Attenuation correction based on the Chang method was performed on MLEM reconstructed images from the water phantom to determine a quantitative measure of the effectiveness of the attenuation correction. Similarly, a NEMAmore » phantom was simulated, and the effectiveness of the attenuation correction was evaluated. Both simulations were carried out using both NaI detectors with an energy resolution of 10% FWHM and Ge detectors with an energy resolution of 1%. Results: Analysis shows that attenuation correction without scatter correction using germanium detectors can reconstruct a small spherical source to within 3.5%. Scatter analysis showed that for standard sized objects in a preclinical scanner, a NaI detector has a scatter-to-primary ratio between 7% and 12.5% compared to between 0.8% and 1.5% for a Ge detector. Preliminary results from line profiles through the NEMA phantom suggest that applying attenuation correction without scatter correction provides acceptable results for the Ge detectors but overestimates the phantom activity using NaI detectors. Due to the decreased scatter, we believe that the spillover ratio for the air and water cylinders in the NEMA phantom will be lower using germanium detectors compared to NaI detectors. Conclusion: This work indicates that the superior energy resolution of germanium detectors allows for less scattered photons to be included within the energy window compared to traditional SPECT detectors. This may allow for quantitative SPECT without implementing scatter correction, reducing uncertainties introduced by scatter correction algorithms. Funding provided by NIH/NIBIB grant R01EB013677; Todd Peterson, Ph.D., has had a research contract with PHDs Co., Knoxville, TN.« less
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Low dose scatter correction for digital chest tomosynthesis
NASA Astrophysics Data System (ADS)
Inscoe, Christina R.; Wu, Gongting; Shan, Jing; Lee, Yueh Z.; Zhou, Otto; Lu, Jianping
2015-03-01
Digital chest tomosynthesis (DCT) provides superior image quality and depth information for thoracic imaging at relatively low dose, though the presence of strong photon scatter degrades the image quality. In most chest radiography, anti-scatter grids are used. However, the grid also blocks a large fraction of the primary beam photons requiring a significantly higher imaging dose for patients. Previously, we have proposed an efficient low dose scatter correction technique using a primary beam sampling apparatus. We implemented the technique in stationary digital breast tomosynthesis, and found the method to be efficient in correcting patient-specific scatter with only 3% increase in dose. In this paper we reported the feasibility study of applying the same technique to chest tomosynthesis. This investigation was performed utilizing phantom and cadaver subjects. The method involves an initial tomosynthesis scan of the object. A lead plate with an array of holes, or primary sampling apparatus (PSA), was placed above the object. A second tomosynthesis scan was performed to measure the primary (scatter-free) transmission. This PSA data was used with the full-field projections to compute the scatter, which was then interpolated to full-field scatter maps unique to each projection angle. Full-field projection images were scatter corrected prior to reconstruction. Projections and reconstruction slices were evaluated and the correction method was found to be effective at improving image quality and practical for clinical implementation.
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Scatter measurement and correction method for cone-beam CT based on single grating scan
NASA Astrophysics Data System (ADS)
Huang, Kuidong; Shi, Wenlong; Wang, Xinyu; Dong, Yin; Chang, Taoqi; Zhang, Hua; Zhang, Dinghua
2017-06-01
In cone-beam computed tomography (CBCT) systems based on flat-panel detector imaging, the presence of scatter significantly reduces the quality of slices. Based on the concept of collimation, this paper presents a scatter measurement and correction method based on single grating scan. First, according to the characteristics of CBCT imaging, the scan method using single grating and the design requirements of the grating are analyzed and figured out. Second, by analyzing the composition of object projection images and object-and-grating projection images, the processing method for the scatter image at single projection angle is proposed. In addition, to avoid additional scan, this paper proposes an angle interpolation method of scatter images to reduce scan cost. Finally, the experimental results show that the scatter images obtained by this method are accurate and reliable, and the effect of scatter correction is obvious. When the additional object-and-grating projection images are collected and interpolated at intervals of 30 deg, the scatter correction error of slices can still be controlled within 3%.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Fan, Peng; Hutton, Brian F.; Holstensson, Maria
2015-12-15
Purpose: The energy spectrum for a cadmium zinc telluride (CZT) detector has a low energy tail due to incomplete charge collection and intercrystal scattering. Due to these solid-state detector effects, scatter would be overestimated if the conventional triple-energy window (TEW) method is used for scatter and crosstalk corrections in CZT-based imaging systems. The objective of this work is to develop a scatter and crosstalk correction method for {sup 99m}Tc/{sup 123}I dual-radionuclide imaging for a CZT-based dedicated cardiac SPECT system with pinhole collimators (GE Discovery NM 530c/570c). Methods: A tailing model was developed to account for the low energy tail effectsmore » of the CZT detector. The parameters of the model were obtained using {sup 99m}Tc and {sup 123}I point source measurements. A scatter model was defined to characterize the relationship between down-scatter and self-scatter projections. The parameters for this model were obtained from Monte Carlo simulation using SIMIND. The tailing and scatter models were further incorporated into a projection count model, and the primary and self-scatter projections of each radionuclide were determined with a maximum likelihood expectation maximization (MLEM) iterative estimation approach. The extracted scatter and crosstalk projections were then incorporated into MLEM image reconstruction as an additive term in forward projection to obtain scatter- and crosstalk-corrected images. The proposed method was validated using Monte Carlo simulation, line source experiment, anthropomorphic torso phantom studies, and patient studies. The performance of the proposed method was also compared to that obtained with the conventional TEW method. Results: Monte Carlo simulations and line source experiment demonstrated that the TEW method overestimated scatter while their proposed method provided more accurate scatter estimation by considering the low energy tail effect. In the phantom study, improved defect contrasts were observed with both correction methods compared to no correction, especially for the images of {sup 99m}Tc in dual-radionuclide imaging where there is heavy contamination from {sup 123}I. In this case, the nontransmural defect contrast was improved from 0.39 to 0.47 with the TEW method and to 0.51 with their proposed method and the transmural defect contrast was improved from 0.62 to 0.74 with the TEW method and to 0.73 with their proposed method. In the patient study, the proposed method provided higher myocardium-to-blood pool contrast than that of the TEW method. Similar to the phantom experiment, the improvement was the most substantial for the images of {sup 99m}Tc in dual-radionuclide imaging. In this case, the myocardium-to-blood pool ratio was improved from 7.0 to 38.3 with the TEW method and to 63.6 with their proposed method. Compared to the TEW method, the proposed method also provided higher count levels in the reconstructed images in both phantom and patient studies, indicating reduced overestimation of scatter. Using the proposed method, consistent reconstruction results were obtained for both single-radionuclide data with scatter correction and dual-radionuclide data with scatter and crosstalk corrections, in both phantom and human studies. Conclusions: The authors demonstrate that the TEW method leads to overestimation in scatter and crosstalk for the CZT-based imaging system while the proposed scatter and crosstalk correction method can provide more accurate self-scatter and down-scatter estimations for quantitative single-radionuclide and dual-radionuclide imaging.« less
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Improved scatter correction with factor analysis for planar and SPECT imaging
NASA Astrophysics Data System (ADS)
Knoll, Peter; Rahmim, Arman; Gültekin, Selma; Šámal, Martin; Ljungberg, Michael; Mirzaei, Siroos; Segars, Paul; Szczupak, Boguslaw
2017-09-01
Quantitative nuclear medicine imaging is an increasingly important frontier. In order to achieve quantitative imaging, various interactions of photons with matter have to be modeled and compensated. Although correction for photon attenuation has been addressed by including x-ray CT scans (accurate), correction for Compton scatter remains an open issue. The inclusion of scattered photons within the energy window used for planar or SPECT data acquisition decreases the contrast of the image. While a number of methods for scatter correction have been proposed in the past, in this work, we propose and assess a novel, user-independent framework applying factor analysis (FA). Extensive Monte Carlo simulations for planar and tomographic imaging were performed using the SIMIND software. Furthermore, planar acquisition of two Petri dishes filled with 99mTc solutions and a Jaszczak phantom study (Data Spectrum Corporation, Durham, NC, USA) using a dual head gamma camera were performed. In order to use FA for scatter correction, we subdivided the applied energy window into a number of sub-windows, serving as input data. FA results in two factor images (photo-peak, scatter) and two corresponding factor curves (energy spectra). Planar and tomographic Jaszczak phantom gamma camera measurements were recorded. The tomographic data (simulations and measurements) were processed for each angular position resulting in a photo-peak and a scatter data set. The reconstructed transaxial slices of the Jaszczak phantom were quantified using an ImageJ plugin. The data obtained by FA showed good agreement with the energy spectra, photo-peak, and scatter images obtained in all Monte Carlo simulated data sets. For comparison, the standard dual-energy window (DEW) approach was additionally applied for scatter correction. FA in comparison with the DEW method results in significant improvements in image accuracy for both planar and tomographic data sets. FA can be used as a user-independent approach for scatter correction in nuclear medicine.
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Large Electroweak Corrections to Vector-Boson Scattering at the Large Hadron Collider.
Biedermann, Benedikt; Denner, Ansgar; Pellen, Mathieu
2017-06-30
For the first time full next-to-leading-order electroweak corrections to off-shell vector-boson scattering are presented. The computation features the complete matrix elements, including all nonresonant and off-shell contributions, to the electroweak process pp→μ^{+}ν_{μ}e^{+}ν_{e}jj and is fully differential. We find surprisingly large corrections, reaching -16% for the fiducial cross section, as an intrinsic feature of the vector-boson-scattering processes. We elucidate the origin of these large electroweak corrections upon using the double-pole approximation and the effective vector-boson approximation along with leading-logarithmic corrections.
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Reversal of photon-scattering errors in atomic qubits.
Akerman, N; Kotler, S; Glickman, Y; Ozeri, R
2012-09-07
Spontaneous photon scattering by an atomic qubit is a notable example of environment-induced error and is a fundamental limit to the fidelity of quantum operations. In the scattering process, the qubit loses its distinctive and coherent character owing to its entanglement with the photon. Using a single trapped ion, we show that by utilizing the information carried by the photon, we are able to coherently reverse this process and correct for the scattering error. We further used quantum process tomography to characterize the photon-scattering error and its correction scheme and demonstrate a correction fidelity greater than 85% whenever a photon was measured.
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TH-A-18C-04: Ultrafast Cone-Beam CT Scatter Correction with GPU-Based Monte Carlo Simulation
DOE Office of Scientific and Technical Information (OSTI.GOV)
Xu, Y; Southern Medical University, Guangzhou; Bai, T
2014-06-15
Purpose: Scatter artifacts severely degrade image quality of cone-beam CT (CBCT). We present an ultrafast scatter correction framework by using GPU-based Monte Carlo (MC) simulation and prior patient CT image, aiming at automatically finish the whole process including both scatter correction and reconstructions within 30 seconds. Methods: The method consists of six steps: 1) FDK reconstruction using raw projection data; 2) Rigid Registration of planning CT to the FDK results; 3) MC scatter calculation at sparse view angles using the planning CT; 4) Interpolation of the calculated scatter signals to other angles; 5) Removal of scatter from the raw projections;more » 6) FDK reconstruction using the scatter-corrected projections. In addition to using GPU to accelerate MC photon simulations, we also use a small number of photons and a down-sampled CT image in simulation to further reduce computation time. A novel denoising algorithm is used to eliminate MC scatter noise caused by low photon numbers. The method is validated on head-and-neck cases with simulated and clinical data. Results: We have studied impacts of photo histories, volume down sampling factors on the accuracy of scatter estimation. The Fourier analysis was conducted to show that scatter images calculated at 31 angles are sufficient to restore those at all angles with <0.1% error. For the simulated case with a resolution of 512×512×100, we simulated 10M photons per angle. The total computation time is 23.77 seconds on a Nvidia GTX Titan GPU. The scatter-induced shading/cupping artifacts are substantially reduced, and the average HU error of a region-of-interest is reduced from 75.9 to 19.0 HU. Similar results were found for a real patient case. Conclusion: A practical ultrafast MC-based CBCT scatter correction scheme is developed. The whole process of scatter correction and reconstruction is accomplished within 30 seconds. This study is supported in part by NIH (1R01CA154747-01), The Core Technology Research in Strategic Emerging Industry, Guangdong, China (2011A081402003)« less
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Analysis of position-dependent Compton scatter in scintimammography with mild compression
NASA Astrophysics Data System (ADS)
Williams, M. B.; Narayanan, D.; More, M. J.; Goodale, P. J.; Majewski, S.; Kieper, D. A.
2003-10-01
In breast scintigraphy using /sup 99m/Tc-sestamibi the relatively low radiotracer uptake in the breast compared to that in other organs such as the heart results in a large fraction of the detected events being Compton scattered gamma-rays. In this study, our goal was to determine whether generalized conclusions regarding scatter-to-primary ratios at various locations within the breast image are possible, and if so, to use them to make explicit scatter corrections to the breast scintigrams. Energy spectra were obtained from patient scans for contiguous regions of interest (ROIs) centered left to right within the image of the breast, and extending from the chest wall edge of the image to the anterior edge. An anthropomorphic torso phantom with fillable internal organs and a compressed-shape breast containing water only was used to obtain realistic position-dependent scatter-only spectra. For each ROI, the measured patient energy spectrum was fitted with a linear combination of the scatter-only spectrum from the anthropomorphic phantom and the scatter-free spectrum from a point source. We found that although there is a very strong dependence on location within the breast of the scatter-to-primary ratio, the spectra are well modeled by a linear combination of position-dependent scatter-only spectra and a position-independent scatter-free spectrum, resulting in a set of position-dependent correction factors. These correction factors can be used along with measured emission spectra from a given breast to correct for the Compton scatter in the scintigrams. However, the large variation among patients in the magnitude of the position-dependent scatter makes the success of universal correction approaches unlikely.
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Scatter correction using a primary modulator on a clinical angiography C-arm CT system.
Bier, Bastian; Berger, Martin; Maier, Andreas; Kachelrieß, Marc; Ritschl, Ludwig; Müller, Kerstin; Choi, Jang-Hwan; Fahrig, Rebecca
2017-09-01
Cone beam computed tomography (CBCT) suffers from a large amount of scatter, resulting in severe scatter artifacts in the reconstructions. Recently, a new scatter correction approach, called improved primary modulator scatter estimation (iPMSE), was introduced. That approach utilizes a primary modulator that is inserted between the X-ray source and the object. This modulation enables estimation of the scatter in the projection domain by optimizing an objective function with respect to the scatter estimate. Up to now the approach has not been implemented on a clinical angiography C-arm CT system. In our work, the iPMSE method is transferred to a clinical C-arm CBCT. Additional processing steps are added in order to compensate for the C-arm scanner motion and the automatic X-ray tube current modulation. These challenges were overcome by establishing a reference modulator database and a block-matching algorithm. Experiments with phantom and experimental in vivo data were performed to evaluate the method. We show that scatter correction using primary modulation is possible on a clinical C-arm CBCT. Scatter artifacts in the reconstructions are reduced with the newly extended method. Compared to a scan with a narrow collimation, our approach showed superior results with an improvement of the contrast and the contrast-to-noise ratio for the phantom experiments. In vivo data are evaluated by comparing the results with a scan with a narrow collimation and with a constant scatter correction approach. Scatter correction using primary modulation is possible on a clinical CBCT by compensating for the scanner motion and the tube current modulation. Scatter artifacts could be reduced in the reconstructions of phantom scans and in experimental in vivo data. © 2017 American Association of Physicists in Medicine.
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Schoen, K; Snow, W M; Kaiser, H; Werner, S A
2005-01-01
The neutron index of refraction is generally derived theoretically in the Fermi approximation. However, the Fermi approximation neglects the effects of the binding of the nuclei of a material as well as multiple scattering. Calculations by Nowak introduced correction terms to the neutron index of refraction that are quadratic in the scattering length and of order 10(-3) fm for hydrogen and deuterium. These correction terms produce a small shift in the final value for the coherent scattering length of H2 in a recent neutron interferometry experiment.
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Liu, Xinming; Shaw, Chris C; Wang, Tianpeng; Chen, Lingyun; Altunbas, Mustafa C; Kappadath, S Cheenu
2006-02-28
We developed and investigated a scanning sampled measurement (SSM) technique for scatter measurement and correction in cone beam breast CT imaging. A cylindrical polypropylene phantom (water equivalent) was mounted on a rotating table in a stationary gantry experimental cone beam breast CT imaging system. A 2-D array of lead beads, with the beads set apart about ~1 cm from each other and slightly tilted vertically, was placed between the object and x-ray source. A series of projection images were acquired as the phantom is rotated 1 degree per projection view and the lead beads array shifted vertically from one projection view to the next. A series of lead bars were also placed at the phantom edge to produce better scatter estimation across the phantom edges. Image signals in the lead beads/bars shadow were used to obtain sampled scatter measurements which were then interpolated to form an estimated scatter distribution across the projection images. The image data behind the lead bead/bar shadows were restored by interpolating image data from two adjacent projection views to form beam-block free projection images. The estimated scatter distribution was then subtracted from the corresponding restored projection image to obtain the scatter removed projection images.Our preliminary experiment has demonstrated that it is feasible to implement SSM technique for scatter estimation and correction for cone beam breast CT imaging. Scatter correction was successfully performed on all projection images using scatter distribution interpolated from SSM and restored projection image data. The resultant scatter corrected projection image data resulted in elevated CT number and largely reduced the cupping effects.
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NASA Technical Reports Server (NTRS)
Gould, R. J.
1979-01-01
Higher-order electromagnetic processes involving particles at ultrahigh energies are discussed, with particular attention given to Compton scattering with the emission of an additional photon (double Compton scattering). Double Compton scattering may have significance in the interaction of a high-energy electron with the cosmic blackbody photon gas. At high energies the cross section for double Compton scattering is large, though this effect is largely canceled by the effects of radiative corrections to ordinary Compton scattering. A similar cancellation takes place for radiative pair production and the associated radiative corrections to the radiationless process. This cancellation is related to the well-known cancellation of the infrared divergence in electrodynamics.
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NASA Astrophysics Data System (ADS)
Pahlevaninezhad, H.; Lee, A. M. D.; Hyun, C.; Lam, S.; MacAulay, C.; Lane, P. M.
2013-03-01
In this paper, we conduct a phantom study for modeling the autofluorescence (AF) properties of tissue. A combined optical coherence tomography (OCT) and AF imaging system is proposed to measure the strength of the AF signal in terms of the scattering layer thickness and concentration. The combined AF-OCT system is capable of estimating the AF loss due to scattering in the epithelium using the thickness and scattering concentration calculated from the co-registered OCT images. We define a correction factor to account for scattering losses in the epithelium and calculate a scatteringcorrected AF signal. We believe the scattering-corrected AF will reduce the diagnostic false-positives rate in the early detection of airway lesions due to confounding factors such as increased epithelial thickness and inflammations.
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Kaneta, Tomohiro; Kurihara, Hideyuki; Hakamatsuka, Takashi; Ito, Hiroshi; Maruoka, Shin; Fukuda, Hiroshi; Takahashi, Shoki; Yamada, Shogo
2004-12-01
123I-15-(p-iodophenyl)-3-(R,S)-methylpentadecanoic acid (BMIPP) and 99mTc-tetrofosmin (TET) are widely used for evaluation of myocardial fatty acid metabolism and perfusion, respectively. ECG-gated TET SPECT is also used for evaluation of myocardial wall motion. These tests are often performed on the same day to minimize both the time required and inconvenience to patients and medical staff. However, as 123I and 99mTc have similar emission energies (159 keV and 140 keV, respectively), it is necessary to consider not only scattered photons, but also primary photons of each radionuclide detected in the wrong window (cross-talk). In this study, we developed and evaluated the effectiveness of a new scatter and cross-talk correction imaging protocol. Fourteen patients with ischemic heart disease or heart failure (8 men and 6 women with a mean age of 69.4 yr, ranging from 45 to 94 yr) were enrolled in this study. In the routine one-day acquisition protocol, BMIPP SPECT was performed in the morning, with TET SPECT performed 4 h later. An additional SPECT was performed just before injection of TET with the energy window for 99mTc. These data correspond to the scatter and cross-talk factor of the next TET SPECT. The correction was performed by subtraction of the scatter and cross-talk factor from TET SPECT. Data are presented as means +/- S.E. Statistical analyses were performed using Wilcoxon's matched-pairs signed-ranks test, and p < 0.05 was considered significant. The percentage of scatter and cross-talk relative to the corrected total count was 26.0 +/- 5.3%. EDV and ESV after correction were significantly greater than those before correction (p = 0.019 and 0.016, respectively). After correction, EF was smaller than that before correction, but the difference was not significant. Perfusion scores (17 segments per heart) were significantly lower after as compared with those before correction (p < 0.001). Scatter and cross-talk correction revealed significant differences in EDV, ESV, and perfusion scores. These observations indicate that scatter and cross-talk correction is required for one-day acquisition of 123I-BMIPP and 99mTc-tetrofosmin SPECT.
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NASA Astrophysics Data System (ADS)
Narita, Y.; Iida, H.; Ebert, S.; Nakamura, T.
1997-12-01
Two independent scatter correction techniques, transmission dependent convolution subtraction (TDCS) and triple-energy window (TEW) method, were evaluated in terms of quantitative accuracy and noise properties using Monte Carlo simulation (EGS4). Emission projections (primary, scatter and scatter plus primary) were simulated for three numerical phantoms for /sup 201/Tl. Data were reconstructed with ordered-subset EM algorithm including noise-less transmission data based attenuation correction. Accuracy of TDCS and TEW scatter corrections were assessed by comparison with simulated true primary data. The uniform cylindrical phantom simulation demonstrated better quantitative accuracy with TDCS than with TEW (-2.0% vs. 16.7%) and better S/N (6.48 vs. 5.05). A uniform ring myocardial phantom simulation demonstrated better homogeneity with TDCS than TEW in the myocardium; i.e., anterior-to-posterior wall count ratios were 0.99 and 0.76 with TDCS and TEW, respectively. For the MCAT phantom, TDCS provided good visual and quantitative agreement with simulated true primary image without noticeably increasing the noise after scatter correction. Overall TDCS proved to be more accurate and less noisy than TEW, facilitating quantitative assessment of physiological functions with SPECT.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Andersen, A; Casares-Magaz, O; Elstroem, U
Purpose: Cone-beam CT (CBCT) imaging may enable image- and dose-guided proton therapy, but is challenged by image artefacts. The aim of this study was to demonstrate the general applicability of a previously developed a priori scatter correction algorithm to allow CBCT-based proton dose calculations. Methods: The a priori scatter correction algorithm used a plan CT (pCT) and raw cone-beam projections acquired with the Varian On-Board Imager. The projections were initially corrected for bow-tie filtering and beam hardening and subsequently reconstructed using the Feldkamp-Davis-Kress algorithm (rawCBCT). The rawCBCTs were intensity normalised before a rigid and deformable registration were applied on themore » pCTs to the rawCBCTs. The resulting images were forward projected onto the same angles as the raw CB projections. The two projections were subtracted from each other, Gaussian and median filtered, and then subtracted from the raw projections and finally reconstructed to the scatter-corrected CBCTs. For evaluation, water equivalent path length (WEPL) maps (from anterior to posterior) were calculated on different reconstructions of three data sets (CB projections and pCT) of three parts of an Alderson phantom. Finally, single beam spot scanning proton plans (0–360 deg gantry angle in steps of 5 deg; using PyTRiP) treating a 5 cm central spherical target in the pCT were re-calculated on scatter-corrected CBCTs with identical targets. Results: The scatter-corrected CBCTs resulted in sub-mm mean WEPL differences relative to the rigid registration of the pCT for all three data sets. These differences were considerably smaller than what was achieved with the regular Varian CBCT reconstruction algorithm (1–9 mm mean WEPL differences). Target coverage in the re-calculated plans was generally improved using the scatter-corrected CBCTs compared to the Varian CBCT reconstruction. Conclusion: We have demonstrated the general applicability of a priori CBCT scatter correction, potentially opening for CBCT-based image/dose-guided proton therapy, including adaptive strategies. Research agreement with Varian Medical Systems, not connected to the present project.« less
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NASA Astrophysics Data System (ADS)
Yang, Kai; Burkett, George, Jr.; Boone, John M.
2014-11-01
The purpose of this research was to develop a method to correct the cupping artifact caused from x-ray scattering and to achieve consistent Hounsfield Unit (HU) values of breast tissues for a dedicated breast CT (bCT) system. The use of a beam passing array (BPA) composed of parallel-holes has been previously proposed for scatter correction in various imaging applications. In this study, we first verified the efficacy and accuracy using BPA to measure the scatter signal on a cone-beam bCT system. A systematic scatter correction approach was then developed by modeling the scatter-to-primary ratio (SPR) in projection images acquired with and without BPA. To quantitatively evaluate the improved accuracy of HU values, different breast tissue-equivalent phantoms were scanned and radially averaged HU profiles through reconstructed planes were evaluated. The dependency of the correction method on object size and number of projections was studied. A simplified application of the proposed method on five clinical patient scans was performed to demonstrate efficacy. For the typical 10-18 cm breast diameters seen in the bCT application, the proposed method can effectively correct for the cupping artifact and reduce the variation of HU values of breast equivalent material from 150 to 40 HU. The measured HU values of 100% glandular tissue, 50/50 glandular/adipose tissue, and 100% adipose tissue were approximately 46, -35, and -94, respectively. It was found that only six BPA projections were necessary to accurately implement this method, and the additional dose requirement is less than 1% of the exam dose. The proposed method can effectively correct for the cupping artifact caused from x-ray scattering and retain consistent HU values of breast tissues.
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CORRECTING FOR INTERSTELLAR SCATTERING DELAY IN HIGH-PRECISION PULSAR TIMING: SIMULATION RESULTS
DOE Office of Scientific and Technical Information (OSTI.GOV)
Palliyaguru, Nipuni; McLaughlin, Maura; Stinebring, Daniel
2015-12-20
Light travel time changes due to gravitational waves (GWs) may be detected within the next decade through precision timing of millisecond pulsars. Removal of frequency-dependent interstellar medium (ISM) delays due to dispersion and scattering is a key issue in the detection process. Current timing algorithms routinely correct pulse times of arrival (TOAs) for time-variable delays due to cold plasma dispersion. However, none of the major pulsar timing groups correct for delays due to scattering from multi-path propagation in the ISM. Scattering introduces a frequency-dependent phase change in the signal that results in pulse broadening and arrival time delays. Any methodmore » to correct the TOA for interstellar propagation effects must be based on multi-frequency measurements that can effectively separate dispersion and scattering delay terms from frequency-independent perturbations such as those due to a GW. Cyclic spectroscopy, first described in an astronomical context by Demorest (2011), is a potentially powerful tool to assist in this multi-frequency decomposition. As a step toward a more comprehensive ISM propagation delay correction, we demonstrate through a simulation that we can accurately recover impulse response functions (IRFs), such as those that would be introduced by multi-path scattering, with a realistic signal-to-noise ratio (S/N). We demonstrate that timing precision is improved when scatter-corrected TOAs are used, under the assumptions of a high S/N and highly scattered signal. We also show that the effect of pulse-to-pulse “jitter” is not a serious problem for IRF reconstruction, at least for jitter levels comparable to those observed in several bright pulsars.« less
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Infrared weak corrections to strongly interacting gauge boson scattering
DOE Office of Scientific and Technical Information (OSTI.GOV)
Ciafaloni, Paolo; Urbano, Alfredo
2010-04-15
We evaluate the impact of electroweak corrections of infrared origin on strongly interacting longitudinal gauge boson scattering, calculating all-order resummed expressions at the double log level. As a working example, we consider the standard model with a heavy Higgs. At energies typical of forthcoming experiments (LHC, International Linear Collider, Compact Linear Collider), the corrections are in the 10%-40% range, with the relative sign depending on the initial state considered and on whether or not additional gauge boson emission is included. We conclude that the effect of radiative electroweak corrections should be included in the analysis of longitudinal gauge boson scattering.
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Mentrup, Detlef; Jockel, Sascha; Menser, Bernd; Neitzel, Ulrich
2016-06-01
The aim of this work was to experimentally compare the contrast improvement factors (CIFs) of a newly developed software-based scatter correction to the CIFs achieved by an antiscatter grid. To this end, three aluminium discs were placed in the lung, the retrocardial and the abdominal areas of a thorax phantom, and digital radiographs of the phantom were acquired both with and without a stationary grid. The contrast generated by the discs was measured in both images, and the CIFs achieved by grid usage were determined for each disc. Additionally, the non-grid images were processed with a scatter correction software. The contrasts generated by the discs were determined in the scatter-corrected images, and the corresponding CIFs were calculated. The CIFs obtained with the grid and with the software were in good agreement. In conclusion, the experiment demonstrates quantitatively that software-based scatter correction allows restoring the image contrast of a non-grid image in a manner comparable with an antiscatter grid. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
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NASA Astrophysics Data System (ADS)
Mohammadi, S. M.; Tavakoli-Anbaran, H.; Zeinali, H. Z.
2017-02-01
The parallel-plate free-air ionization chamber termed FAC-IR-300 was designed at the Atomic Energy Organization of Iran, AEOI. This chamber is used for low and medium X-ray dosimetry on the primary standard level. In order to evaluate the air-kerma, some correction factors such as electron-loss correction factor (ke) and photon scattering correction factor (ksc) are needed. ke factor corrects the charge loss from the collecting volume and ksc factor corrects the scattering of photons into collecting volume. In this work ke and ksc were estimated by Monte Carlo simulation. These correction factors are calculated for mono-energy photon. As a result of the simulation data, the ke and ksc values for FAC-IR-300 ionization chamber are 1.0704 and 0.9982, respectively.
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Han, Zhen-Xia; Shi, Qing; Wang, Da-Kun; Li, Dong; Lyu, Ming
2013-10-01
Bone marrow (BM) and umbilical cord (UC) are the major sources of mesenchymal stem cells for therapeutics. This study was aimed to compare the basic biologic characteristics of bone marrow-derived and umbilical cord derived-mesenchymal stem cells (BM-MSC and UC-MSC) and their immunosuppressive capability in vitro. The BM-MSC and UC-MSC were cultured and amplified under same culture condition. The growth kinetics, phenotypic characteristics and immunosuppressive effects of UC-MSC were compared with those of BM-MSC.Gene chip was used to compare the genes differentially expressed between UC-MSC and BM-MSC. The results showed that UC-MSC shared most of the characteristics of BM-MSC, including morphology and immunophenotype. UC-MSC could be ready expanded for 30 passages without visible changes. However, BM-MSC grew slowly, and the mean doubling time increased notably after passage 6. Both UC-MSC and BM-MSC could inhibit phytohemagglutinin-stimulated peripheral blood mononuclear cell proliferation, in which BM-MSC mediated more inhibitory effect. Compared with UC-MSC, BM-MSC expressed more genes associated with immune response. Meanwhile, the categories of up-regulated genes in UC-MSC were concentrated in organ development and growth. It is concluded that the higher proliferation capacity, low human leukocyte antigen-ABC expression and immunosuppression make UC-MSC an excellent alternative to BM-MSC for cell therapy. The differences between BM-MSC and UC-MSC gene expressions can be explained by their ontogeny and different microenvironment in origin tissue. These differences can affect their efficacy in different therapeutic applications.
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Tewari, Deepshikha; Khan, Mohd Parvez; Sagar, Nitin; China, Shyamsundar P; Singh, Atul K; Kheruka, Subhash C; Barai, Sukanta; Tewari, Mahesh C; Nagar, Geet K; Vishwakarma, Achchhe L; Ogechukwu, Omeje E; Bellare, Jayesh R; Gambhir, Sanjay; Chattopadhyay, Naibedya
2015-04-01
We investigated deleterious changes that take place in mesenchymal stem cells (MSC) and its fracture healing competence in ovariectomy (Ovx)-induced osteopenia. MSC from bone marrow (BM) of ovary intact (control) and Ovx rats was isolated. (99m)Tc-HMPAO (Technitium hexamethylpropylene amine oxime) labeled MSC was systemically transplanted to rats and fracture tropism assessed by SPECT/CT. PKH26 labeled MSC (PKH26-MSC) was bound in scaffold and applied to fracture site (drill-hole in femur metaphysis). Osteoinduction was quantified by calcein binding and microcomputed tomography. Estrogen receptor (ER) antagonist, fulvestrant was used to determine ER dependence of osteo-induction by MSC. BM-MSC number was strikingly reduced and doubling time increased in Ovx rats compared to control. SPECT/CT showed reduced localization of (99m)Tc-HMPAO labeled MSC to the fracture site, 3 h post-transplantation in Ovx rats as compared with controls. Post-transplantation, Ovx MSC labeled with PKH26 (Ovx PKH26-MSC) localized less to fracture site than control PKH26-MSC. Transplantation of either control or Ovx MSC enhanced calcein binding and bone volume at the callus of control rats over placebo group however Ovx MSC had lower efficacy than control MSC. Fulvestrant blocked osteoinduction by control MSC. When scaffold bound MSC was applied to fracture, osteoinduction by Ovx PKH26-MSC was less than control PKH26-MSC. In Ovx rats, control MSC/E2 treatment but not Ovx MSC showed osteoinduction. Regenerated bone was irregularly deposited in Ovx MSC group. In conclusion, Ovx is associated with diminished BM-MSC number and its growth, and Ovx MSC displays impaired engraftment to fracture and osteoinduction besides disordered bone regeneration.
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NASA Astrophysics Data System (ADS)
Meyer, Michael; Kalender, Willi A.; Kyriakou, Yiannis
2010-01-01
Scattered radiation is a major source of artifacts in flat detector computed tomography (FDCT) due to the increased irradiated volumes. We propose a fast projection-based algorithm for correction of scatter artifacts. The presented algorithm combines a convolution method to determine the spatial distribution of the scatter intensity distribution with an object-size-dependent scaling of the scatter intensity distributions using a priori information generated by Monte Carlo simulations. A projection-based (PBSE) and an image-based (IBSE) strategy for size estimation of the scanned object are presented. Both strategies provide good correction and comparable results; the faster PBSE strategy is recommended. Even with such a fast and simple algorithm that in the PBSE variant does not rely on reconstructed volumes or scatter measurements, it is possible to provide a reasonable scatter correction even for truncated scans. For both simulations and measurements, scatter artifacts were significantly reduced and the algorithm showed stable behavior in the z-direction. For simulated voxelized head, hip and thorax phantoms, a figure of merit Q of 0.82, 0.76 and 0.77 was reached, respectively (Q = 0 for uncorrected, Q = 1 for ideal). For a water phantom with 15 cm diameter, for example, a cupping reduction from 10.8% down to 2.1% was achieved. The performance of the correction method has limitations in the case of measurements using non-ideal detectors, intensity calibration, etc. An iterative approach to overcome most of these limitations was proposed. This approach is based on root finding of a cupping metric and may be useful for other scatter correction methods as well. By this optimization, cupping of the measured water phantom was further reduced down to 0.9%. The algorithm was evaluated on a commercial system including truncated and non-homogeneous clinically relevant objects.
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Shen, Tingting; Ye, Lanhan; Kong, Wenwen; Wang, Wei; Liu, Xiaodan
2018-01-01
Fast detection of toxic metals in crops is important for monitoring pollution and ensuring food safety. In this study, laser-induced breakdown spectroscopy (LIBS) was used to detect the chromium content in rice leaves. We investigated the influence of laser wavelength (532 nm and 1064 nm excitation), along with the variations of delay time, pulse energy, and lens-to-sample distance (LTSD), on the signal (sensitivity and stability) and plasma features (temperature and electron density). With the optimized experimental parameters, univariate analysis was used for quantifying the chromium content, and several preprocessing methods (including background normalization, area normalization, multiplicative scatter correction (MSC) transformation and standardized normal variate (SNV) transformation were used to further improve the analytical performance. The results indicated that 532 nm excitation showed better sensitivity than 1064 nm excitation, with a detection limit around two times lower. However, the prediction accuracy for both excitation wavelengths was similar. The best result, with a correlation coefficient of 0.9849, root-mean-square error of 3.89 mg/kg and detection limit of 2.72 mg/kg, was obtained using the SNV transformed signal (Cr I 425.43 nm) induced by 532 nm excitation. The results indicate the inspiring capability of LIBS for toxic metals detection in plant materials. PMID:29463032
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NASA Astrophysics Data System (ADS)
Lin, Z. D.; Wang, Y. B.; Wang, R. J.; Wang, L. S.; Lu, C. P.; Zhang, Z. Y.; Song, L. T.; Liu, Y.
2017-07-01
A total of 130 topsoil samples collected from Guoyang County, Anhui Province, China, were used to establish a Vis-NIR model for the prediction of organic matter content (OMC) in lime concretion black soils. Different spectral pretreatments were applied for minimizing the irrelevant and useless information of the spectra and increasing the spectra correlation with the measured values. Subsequently, the Kennard-Stone (KS) method and sample set partitioning based on joint x-y distances (SPXY) were used to select the training set. Successive projection algorithm (SPA) and genetic algorithm (GA) were then applied for wavelength optimization. Finally, the principal component regression (PCR) model was constructed, in which the optimal number of principal components was determined using the leave-one-out cross validation technique. The results show that the combination of the Savitzky-Golay (SG) filter for smoothing and multiplicative scatter correction (MSC) can eliminate the effect of noise and baseline drift; the SPXY method is preferable to KS in the sample selection; both the SPA and the GA can significantly reduce the number of wavelength variables and favorably increase the accuracy, especially GA, which greatly improved the prediction accuracy of soil OMC with Rcc, RMSEP, and RPD up to 0.9316, 0.2142, and 2.3195, respectively.
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Liu, Xue-Mei; Liu, Jian-She
2012-11-01
Visible infrared spectroscopy (Vis/SW-NIRS) was investigated in the present study for measurement accuracy of soil properties,namely, available nitrogen(N) and available potassium(K). Three types of pretreatments including standard normal variate (SNV), multiplicative scattering correction (MSC) and Savitzky-Golay smoothing+first derivative were adopted to eliminate the system noises and external disturbances. Then partial least squares (PLS) and least squares-support vector machine (LS-SVM) models analysis were implemented for calibration models. Simultaneously, the performance of least squares-support vector machine (LS-SVM) models was compared with three kinds of inputs, including PCA(PCs), latent variables (LVs), and effective wavelengths (EWs). The results indicated that all LS-SVM models outperformed PLS models. The performance of the model was evaluated by the correlation coefficient (r2) and RMSEP. The optimal EWs-LS-SVM models were achieved, and the correlation coefficient (r2) and RMSEP were 0.82 and 17.2 for N and 0.72 and 15.0 for K, respectively. The results indicated that visible and short wave-near infrared spectroscopy (Vis/SW-NIRS)(325-1 075 nm) combined with LS-SVM could be utilized as a precision method for the determination of soil properties.
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Müller, Aline Lima Hermes; Picoloto, Rochele Sogari; de Azevedo Mello, Paola; Ferrão, Marco Flores; de Fátima Pereira dos Santos, Maria; Guimarães, Regina Célia Lourenço; Müller, Edson Irineu; Flores, Erico Marlon Moraes
2012-04-01
Total sulfur concentration was determined in atmospheric residue (AR) and vacuum residue (VR) samples obtained from petroleum distillation process by Fourier transform infrared spectroscopy with attenuated total reflectance (FT-IR/ATR) in association with chemometric methods. Calibration and prediction set consisted of 40 and 20 samples, respectively. Calibration models were developed using two variable selection models: interval partial least squares (iPLS) and synergy interval partial least squares (siPLS). Different treatments and pre-processing steps were also evaluated for the development of models. The pre-treatment based on multiplicative scatter correction (MSC) and the mean centered data were selected for models construction. The use of siPLS as variable selection method provided a model with root mean square error of prediction (RMSEP) values significantly better than those obtained by PLS model using all variables. The best model was obtained using siPLS algorithm with spectra divided in 20 intervals and combinations of 3 intervals (911-824, 823-736 and 737-650 cm(-1)). This model produced a RMSECV of 400 mg kg(-1) S and RMSEP of 420 mg kg(-1) S, showing a correlation coefficient of 0.990. Copyright © 2011 Elsevier B.V. All rights reserved.
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Data consistency-driven scatter kernel optimization for x-ray cone-beam CT
NASA Astrophysics Data System (ADS)
Kim, Changhwan; Park, Miran; Sung, Younghun; Lee, Jaehak; Choi, Jiyoung; Cho, Seungryong
2015-08-01
Accurate and efficient scatter correction is essential for acquisition of high-quality x-ray cone-beam CT (CBCT) images for various applications. This study was conducted to demonstrate the feasibility of using the data consistency condition (DCC) as a criterion for scatter kernel optimization in scatter deconvolution methods in CBCT. As in CBCT, data consistency in the mid-plane is primarily challenged by scatter, we utilized data consistency to confirm the degree of scatter correction and to steer the update in iterative kernel optimization. By means of the parallel-beam DCC via fan-parallel rebinning, we iteratively optimized the scatter kernel parameters, using a particle swarm optimization algorithm for its computational efficiency and excellent convergence. The proposed method was validated by a simulation study using the XCAT numerical phantom and also by experimental studies using the ACS head phantom and the pelvic part of the Rando phantom. The results showed that the proposed method can effectively improve the accuracy of deconvolution-based scatter correction. Quantitative assessments of image quality parameters such as contrast and structure similarity (SSIM) revealed that the optimally selected scatter kernel improves the contrast of scatter-free images by up to 99.5%, 94.4%, and 84.4%, and of the SSIM in an XCAT study, an ACS head phantom study, and a pelvis phantom study by up to 96.7%, 90.5%, and 87.8%, respectively. The proposed method can achieve accurate and efficient scatter correction from a single cone-beam scan without need of any auxiliary hardware or additional experimentation.
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Fractal scaling laws of black carbon aerosol and their influence on spectral radiative properties
NASA Astrophysics Data System (ADS)
Tiwari, S.; Chakrabarty, R. K.; Heinson, W.
2016-12-01
Current estimates of the direct radiative forcing for Black Carbon (BC) aerosol span over a poorly constrained range between 0.2 and 1 W.m-2. To improve this large uncertainty, tighter constraints need to be placed on BC's key wavelength-dependent optical properties, namely, the absorption (MAC) and scattering (MSC) cross sections per unit mass and hemispherical upscatter fraction (β; a dimensionless scattering directionality parameter). These parameters are very sensitive to changes in particle morphology and complex refractive index nindex. Their interplay determines the magnitude of net positive or negative radiative forcing efficiencies. The current approach among climate modelers for estimating MAC and MSC values of BC is from their optical cross-sections calculated assuming spherical particle morphology with homogeneous, constant-valued refractive index in the visible solar spectrum. The β values are typically assumed to be a constant across this spectrum. This approach, while being computationally inexpensive and convenient, ignores the inherent fractal morphology of BC and its scaling behaviors, and resulting optical properties. In this talk, I will present recent results from my laboratory on determination of the fractal scaling laws of BC aggregate packing density and its complex refractive index for size spanning across three orders of magnitude, and their effects on spectral (Visible-infrared wavelength) scaling of MAC, MSC, and β values. Our experiments synergistically combined novel BC generation techniques, aggregation models, contact-free multi-wavelength optical measurements, and electron microscopy analysis. The scale dependence of nindex on aggregate size followed power-law exponents of -1.4 and -0.5 for sub- and super-micron size aggregates, respectively. The spherical Rayleigh-optics approximation limits, used by climate models for spectral extrapolation of BC optical cross-sections and deconvolution of multi-species mixing ratios, are redefined using the concept of phase shift parameter. I will highlight the importance of size-dependent β values and its role in offsetting the strong light absorbing nature of BC. Finally, the errors introduced in forcing efficiency calculations of BC by assuming spherical homogeneous morphology will be evaluated.
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Correction of scatter in megavoltage cone-beam CT
NASA Astrophysics Data System (ADS)
Spies, L.; Ebert, M.; Groh, B. A.; Hesse, B. M.; Bortfeld, T.
2001-03-01
The role of scatter in a cone-beam computed tomography system using the therapeutic beam of a medical linear accelerator and a commercial electronic portal imaging device (EPID) is investigated. A scatter correction method is presented which is based on a superposition of Monte Carlo generated scatter kernels. The kernels are adapted to both the spectral response of the EPID and the dimensions of the phantom being scanned. The method is part of a calibration procedure which converts the measured transmission data acquired for each projection angle into water-equivalent thicknesses. Tomographic reconstruction of the projections then yields an estimate of the electron density distribution of the phantom. It is found that scatter produces cupping artefacts in the reconstructed tomograms. Furthermore, reconstructed electron densities deviate greatly (by about 30%) from their expected values. The scatter correction method removes the cupping artefacts and decreases the deviations from 30% down to about 8%.
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Messinian Salinity Crisis and basin fluid flow
NASA Astrophysics Data System (ADS)
Bertoni, Claudia; Cartwight, Joe
2014-05-01
Syn- and post-depositional movement of fluids through sediments is one of the least understood aspects in the evolution of a basin. The conventional hydrostratigraphic view on marine sedimentary basins assumes that compactional and meteoric groundwater fluid circulation drives fluid movement and defines its timing. However, in the past few years, several examples of instantaneous and catastrophic release of fluids have been observed even through low-permeability sediments. A particularly complex case-study involves the presence of giant salt bodies in the depocentres of marine basins. Evaporites dramatically change the hydrostratigraphy and fluid-dynamics of the basin, and influence the P/T regimes, e.g. through changes in the geothermal gradient and in the compaction of underlying sediments. Our paper reviews the impact of the Messinian Salinity Crisis (MSC) and evaporites on fluid flow in the Mediterranean sub-basins. The analysis of geological and geophysical sub-surface data provides examples from this basin, and the comparison with analogues in other well-known evaporitic provinces. During the MSC, massive sea-level changes occurred in a relatively limited time interval, and affected the balance of fluid dynamics, e.g. with sudden release or unusual trapping of fluids. Fluid expulsion events are here analysed and classified in relation to the long and short-term effects of the MSC. Our main aim is to build a framework for the correct identification of the fluid flow-related events, and their genetic mechanisms. On basin margins, where evaporites are thin or absent, the sea-level changes associated with the MSC force a rapid basinward shift of the mixing zone of meteoric/gravity flow and saline/compactional flow, 100s-km away from its pre-MSC position. This phenomenon changes the geometry of converging flows, creates hydraulic traps for fluids, and triggers specific diagenetic reactions in pre-MSC deep marine sediments. In basin-centre settings, unloading and re-loading of water associated to the sea-level changes leads to the sudden release of focused fluids, enhancing pockmark formation, evaporite dissolution, gas-hydrate dissociation and methane venting. After the MSC, and in the long-term basin evolution, the aquitard effect of the thick evaporites also created favourable condition for the development of overpressures in the pre-MSC sediments. However, the traditional view of saline giants as impermeable barriers to fluid flow has been challenged in recent years, by the documented evidence of fluid migration pathways through thick evaporites. Ultimately, these events can lead not only to fluid, but also to sediment remobilisation. The review here presented has applications as a tool for identifying, quantifying and understanding controls and timing of fluid dynamics in marine basins hosting extensive evaporitic series.
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TLR4 plays a crucial role in MSC-induced inhibition of NK cell function
DOE Office of Scientific and Technical Information (OSTI.GOV)
Lu, Ying; Liu, Jin; Liu, Yang
2015-08-21
Mesenchymal stem cells (MSC) are a kind of stromal cell within the tumor microenvironment. In our research, MSC derived from acute myeloid leukemia patients' bone marrow (AML-MSC) and lung cancer tissues (LC-MSC) as well as normal bone marrow-derived MSC (BM-MSC) cultured in conditioned medium of HeLa cells were found to have higher expressions of Toll-like receptor (TLR4) mRNA compared with BM-MSC. The sorted TLR4-positive MSC (TLR4+ MSC) differed in cytokine (interleukin-6, interleukin-8, and monocyte chemoattractant protein-1) secretion from those of unsorted MSC. MSC was reported to inhibit natural killer (NK) cell proliferation and function. In this research, we confirmed thatmore » TLR4+ MSC aggravate this suppression. Furthermore, when TLR4 in the sorted cells were stimulated by LPS or following blocked by antibody, the suppression on NK cell proliferation and cytotoxicity were more intensive or recovered respectively. Compared to unsorted MSC, NKG2D receptor expression on NK cells were also inhibited by TLR4+ MSC. These findings suggest that activation of TLR4 pathway is important for TLR4+ MSC and MSC to obstruct anti-tumor immunity by inhibiting NK cell function, which may provide a potential stroma-targeted tumor therapy. - Highlights: • TLR4+ MSC inhibit NK cell proliferation in vivo and in vitro. • TLR4+ MSC inhibit NKG2D expression on NK cells and NK cell cytotoxicity. • The distinguished cytokine expression of TLR4+ MSC may contribute to the inhibition on NK cell function.« less
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Scatter characterization and correction for simultaneous multiple small-animal PET imaging.
Prasad, Rameshwar; Zaidi, Habib
2014-04-01
The rapid growth and usage of small-animal positron emission tomography (PET) in molecular imaging research has led to increased demand on PET scanner's time. One potential solution to increase throughput is to scan multiple rodents simultaneously. However, this is achieved at the expense of deterioration of image quality and loss of quantitative accuracy owing to enhanced effects of photon attenuation and Compton scattering. The purpose of this work is, first, to characterize the magnitude and spatial distribution of the scatter component in small-animal PET imaging when scanning single and multiple rodents simultaneously and, second, to assess the relevance and evaluate the performance of scatter correction under similar conditions. The LabPET™-8 scanner was modelled as realistically as possible using Geant4 Application for Tomographic Emission Monte Carlo simulation platform. Monte Carlo simulations allow the separation of unscattered and scattered coincidences and as such enable detailed assessment of the scatter component and its origin. Simple shape-based and more realistic voxel-based phantoms were used to simulate single and multiple PET imaging studies. The modelled scatter component using the single-scatter simulation technique was compared to Monte Carlo simulation results. PET images were also corrected for attenuation and the combined effect of attenuation and scatter on single and multiple small-animal PET imaging evaluated in terms of image quality and quantitative accuracy. A good agreement was observed between calculated and Monte Carlo simulated scatter profiles for single- and multiple-subject imaging. In the LabPET™-8 scanner, the detector covering material (kovar) contributed the maximum amount of scatter events while the scatter contribution due to lead shielding is negligible. The out-of field-of-view (FOV) scatter fraction (SF) is 1.70, 0.76, and 0.11% for lower energy thresholds of 250, 350, and 400 keV, respectively. The increase in SF ranged between 25 and 64% when imaging multiple subjects (three to five) of different size simultaneously in comparison to imaging a single subject. The spill-over ratio (SOR) increases with increasing the number of subjects in the FOV. Scatter correction improved the SOR for both water and air cold compartments of single and multiple imaging studies. The recovery coefficients for different body parts of the mouse whole-body and rat whole-body anatomical models were improved for multiple imaging studies following scatter correction. The magnitude and spatial distribution of the scatter component in small-animal PET imaging of single and multiple subjects simultaneously were characterized, and its impact was evaluated in different situations. Scatter correction improves PET image quality and quantitative accuracy for single rat and simultaneous multiple mice and rat imaging studies, whereas its impact is insignificant in single mouse imaging.
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Evaluation of attenuation and scatter correction requirements in small animal PET and SPECT imaging
NASA Astrophysics Data System (ADS)
Konik, Arda Bekir
Positron emission tomography (PET) and single photon emission tomography (SPECT) are two nuclear emission-imaging modalities that rely on the detection of high-energy photons emitted from radiotracers administered to the subject. The majority of these photons are attenuated (absorbed or scattered) in the body, resulting in count losses or deviations from true detection, which in turn degrades the accuracy of images. In clinical emission tomography, sophisticated correction methods are often required employing additional x-ray CT or radionuclide transmission scans. Having proven their potential in both clinical and research areas, both PET and SPECT are being adapted for small animal imaging. However, despite the growing interest in small animal emission tomography, little scientific information exists about the accuracy of these correction methods on smaller size objects, and what level of correction is required. The purpose of this work is to determine the role of attenuation and scatter corrections as a function of object size through simulations. The simulations were performed using Interactive Data Language (IDL) and a Monte Carlo based package, Geant4 application for emission tomography (GATE). In IDL simulations, PET and SPECT data acquisition were modeled in the presence of attenuation. A mathematical emission and attenuation phantom approximating a thorax slice and slices from real PET/CT data were scaled to 5 different sizes (i.e., human, dog, rabbit, rat and mouse). The simulated emission data collected from these objects were reconstructed. The reconstructed images, with and without attenuation correction, were compared to the ideal (i.e., non-attenuated) reconstruction. Next, using GATE, scatter fraction values (the ratio of the scatter counts to the total counts) of PET and SPECT scanners were measured for various sizes of NEMA (cylindrical phantoms representing small animals and human), MOBY (realistic mouse/rat model) and XCAT (realistic human model) digital phantoms. In addition, PET projection files for different sizes of MOBY phantoms were reconstructed in 6 different conditions including attenuation and scatter corrections. Selected regions were analyzed for these different reconstruction conditions and object sizes. Finally, real mouse data from the real version of the same small animal PET scanner we modeled in our simulations were analyzed for similar reconstruction conditions. Both our IDL and GATE simulations showed that, for small animal PET and SPECT, even the smallest size objects (˜2 cm diameter) showed ˜15% error when both attenuation and scatter were not corrected. However, a simple attenuation correction using a uniform attenuation map and object boundary obtained from emission data significantly reduces this error in non-lung regions (˜1% for smallest size and ˜6% for largest size). In lungs, emissions values were overestimated when only attenuation correction was performed. In addition, we did not observe any significant improvement between the uses of uniform or actual attenuation map (e.g., only ˜0.5% for largest size in PET studies). The scatter correction was not significant for smaller size objects, but became increasingly important for larger sizes objects. These results suggest that for all mouse sizes and most rat sizes, uniform attenuation correction can be performed using emission data only. For smaller sizes up to ˜ 4 cm, scatter correction is not required even in lung regions. For larger sizes if accurate quantization needed, additional transmission scan may be required to estimate an accurate attenuation map for both attenuation and scatter corrections.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Bootsma, G. J., E-mail: Gregory.Bootsma@rmp.uhn.on.ca; Verhaegen, F.; Medical Physics Unit, Department of Oncology, McGill University, Montreal, Quebec H3G 1A4
2015-01-15
Purpose: X-ray scatter is a significant impediment to image quality improvements in cone-beam CT (CBCT). The authors present and demonstrate a novel scatter correction algorithm using a scatter estimation method that simultaneously combines multiple Monte Carlo (MC) CBCT simulations through the use of a concurrently evaluated fitting function, referred to as concurrent MC fitting (CMCF). Methods: The CMCF method uses concurrently run MC CBCT scatter projection simulations that are a subset of the projection angles used in the projection set, P, to be corrected. The scattered photons reaching the detector in each MC simulation are simultaneously aggregated by an algorithmmore » which computes the scatter detector response, S{sub MC}. S{sub MC} is fit to a function, S{sub F}, and if the fit of S{sub F} is within a specified goodness of fit (GOF), the simulations are terminated. The fit, S{sub F}, is then used to interpolate the scatter distribution over all pixel locations for every projection angle in the set P. The CMCF algorithm was tested using a frequency limited sum of sines and cosines as the fitting function on both simulated and measured data. The simulated data consisted of an anthropomorphic head and a pelvis phantom created from CT data, simulated with and without the use of a compensator. The measured data were a pelvis scan of a phantom and patient taken on an Elekta Synergy platform. The simulated data were used to evaluate various GOF metrics as well as determine a suitable fitness value. The simulated data were also used to quantitatively evaluate the image quality improvements provided by the CMCF method. A qualitative analysis was performed on the measured data by comparing the CMCF scatter corrected reconstruction to the original uncorrected and corrected by a constant scatter correction reconstruction, as well as a reconstruction created using a set of projections taken with a small cone angle. Results: Pearson’s correlation, r, proved to be a suitable GOF metric with strong correlation with the actual error of the scatter fit, S{sub F}. Fitting the scatter distribution to a limited sum of sine and cosine functions using a low-pass filtered fast Fourier transform provided a computationally efficient and accurate fit. The CMCF algorithm reduces the number of photon histories required by over four orders of magnitude. The simulated experiments showed that using a compensator reduced the computational time by a factor between 1.5 and 1.75. The scatter estimates for the simulated and measured data were computed between 35–93 s and 114–122 s, respectively, using 16 Intel Xeon cores (3.0 GHz). The CMCF scatter correction improved the contrast-to-noise ratio by 10%–50% and reduced the reconstruction error to under 3% for the simulated phantoms. Conclusions: The novel CMCF algorithm significantly reduces the computation time required to estimate the scatter distribution by reducing the statistical noise in the MC scatter estimate and limiting the number of projection angles that must be simulated. Using the scatter estimate provided by the CMCF algorithm to correct both simulated and real projection data showed improved reconstruction image quality.« less
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A model-based scatter artifacts correction for cone beam CT
DOE Office of Scientific and Technical Information (OSTI.GOV)
Zhao, Wei; Zhu, Jun; Wang, Luyao
2016-04-15
Purpose: Due to the increased axial coverage of multislice computed tomography (CT) and the introduction of flat detectors, the size of x-ray illumination fields has grown dramatically, causing an increase in scatter radiation. For CT imaging, scatter is a significant issue that introduces shading artifact, streaks, as well as reduced contrast and Hounsfield Units (HU) accuracy. The purpose of this work is to provide a fast and accurate scatter artifacts correction algorithm for cone beam CT (CBCT) imaging. Methods: The method starts with an estimation of coarse scatter profiles for a set of CBCT data in either image domain ormore » projection domain. A denoising algorithm designed specifically for Poisson signals is then applied to derive the final scatter distribution. Qualitative and quantitative evaluations using thorax and abdomen phantoms with Monte Carlo (MC) simulations, experimental Catphan phantom data, and in vivo human data acquired for a clinical image guided radiation therapy were performed. Scatter correction in both projection domain and image domain was conducted and the influences of segmentation method, mismatched attenuation coefficients, and spectrum model as well as parameter selection were also investigated. Results: Results show that the proposed algorithm can significantly reduce scatter artifacts and recover the correct HU in either projection domain or image domain. For the MC thorax phantom study, four-components segmentation yields the best results, while the results of three-components segmentation are still acceptable. The parameters (iteration number K and weight β) affect the accuracy of the scatter correction and the results get improved as K and β increase. It was found that variations in attenuation coefficient accuracies only slightly impact the performance of the proposed processing. For the Catphan phantom data, the mean value over all pixels in the residual image is reduced from −21.8 to −0.2 HU and 0.7 HU for projection domain and image domain, respectively. The contrast of the in vivo human images is greatly improved after correction. Conclusions: The software-based technique has a number of advantages, such as high computational efficiency and accuracy, and the capability of performing scatter correction without modifying the clinical workflow (i.e., no extra scan/measurement data are needed) or modifying the imaging hardware. When implemented practically, this should improve the accuracy of CBCT image quantitation and significantly impact CBCT-based interventional procedures and adaptive radiation therapy.« less
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NASA Astrophysics Data System (ADS)
Fishkin, Joshua B.; So, Peter T. C.; Cerussi, Albert E.; Gratton, Enrico; Fantini, Sergio; Franceschini, Maria Angela
1995-03-01
We have measured the optical absorption and scattering coefficient spectra of a multiple-scattering medium (i.e., a biological tissue-simulating phantom comprising a lipid colloid) containing methemoglobin by using frequency-domain techniques. The methemoglobin absorption spectrum determined in the multiple-scattering medium is in excellent agreement with a corrected methemoglobin absorption spectrum obtained from a steady-state spectrophotometer measurement of the optical density of a minimally scattering medium. The determination of the corrected methemoglobin absorption spectrum takes into account the scattering from impurities in the methemoglobin solution containing no lipid colloid. Frequency-domain techniques allow for the separation of the absorbing from the scattering properties of multiple-scattering media, and these techniques thus provide an absolute
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NASA Astrophysics Data System (ADS)
Kurata, Tomohiro; Oda, Shigeto; Kawahira, Hiroshi; Haneishi, Hideaki
2016-12-01
We have previously proposed an estimation method of intravascular oxygen saturation (SO_2) from the images obtained by sidestream dark-field (SDF) imaging (we call it SDF oximetry) and we investigated its fundamental characteristics by Monte Carlo simulation. In this paper, we propose a correction method for scattering by the tissue and performed experiments with turbid phantoms as well as Monte Carlo simulation experiments to investigate the influence of the tissue scattering in the SDF imaging. In the estimation method, we used modified extinction coefficients of hemoglobin called average extinction coefficients (AECs) to correct the influence from the bandwidth of the illumination sources, the imaging camera characteristics, and the tissue scattering. We estimate the scattering coefficient of the tissue from the maximum slope of pixel value profile along a line perpendicular to the blood vessel running direction in an SDF image and correct AECs using the scattering coefficient. To evaluate the proposed method, we developed a trial SDF probe to obtain three-band images by switching multicolor light-emitting diodes and obtained the image of turbid phantoms comprised of agar powder, fat emulsion, and bovine blood-filled glass tubes. As a result, we found that the increase of scattering by the phantom body brought about the decrease of the AECs. The experimental results showed that the use of suitable values for AECs led to more accurate SO_2 estimation. We also confirmed the validity of the proposed correction method to improve the accuracy of the SO_2 estimation.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Wang, A; Paysan, P; Brehm, M
2016-06-15
Purpose: To improve CBCT image quality for image-guided radiotherapy by applying advanced reconstruction algorithms to overcome scatter, noise, and artifact limitations Methods: CBCT is used extensively for patient setup in radiotherapy. However, image quality generally falls short of diagnostic CT, limiting soft-tissue based positioning and potential applications such as adaptive radiotherapy. The conventional TrueBeam CBCT reconstructor uses a basic scatter correction and FDK reconstruction, resulting in residual scatter artifacts, suboptimal image noise characteristics, and other artifacts like cone-beam artifacts. We have developed an advanced scatter correction that uses a finite-element solver (AcurosCTS) to model the behavior of photons as theymore » pass (and scatter) through the object. Furthermore, iterative reconstruction is applied to the scatter-corrected projections, enforcing data consistency with statistical weighting and applying an edge-preserving image regularizer to reduce image noise. The combined algorithms have been implemented on a GPU. CBCT projections from clinically operating TrueBeam systems have been used to compare image quality between the conventional and improved reconstruction methods. Planning CT images of the same patients have also been compared. Results: The advanced scatter correction removes shading and inhomogeneity artifacts, reducing the scatter artifact from 99.5 HU to 13.7 HU in a typical pelvis case. Iterative reconstruction provides further benefit by reducing image noise and eliminating streak artifacts, thereby improving soft-tissue visualization. In a clinical head and pelvis CBCT, the noise was reduced by 43% and 48%, respectively, with no change in spatial resolution (assessed visually). Additional benefits include reduction of cone-beam artifacts and reduction of metal artifacts due to intrinsic downweighting of corrupted rays. Conclusion: The combination of an advanced scatter correction with iterative reconstruction substantially improves CBCT image quality. It is anticipated that clinically acceptable reconstruction times will result from a multi-GPU implementation (the algorithms are under active development and not yet commercially available). All authors are employees of and (may) own stock of Varian Medical Systems.« less
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NASA Astrophysics Data System (ADS)
Busi, Matteo; Olsen, Ulrik L.; Knudsen, Erik B.; Frisvad, Jeppe R.; Kehres, Jan; Dreier, Erik S.; Khalil, Mohamad; Haldrup, Kristoffer
2018-03-01
Spectral computed tomography is an emerging imaging method that involves using recently developed energy discriminating photon-counting detectors (PCDs). This technique enables measurements at isolated high-energy ranges, in which the dominating undergoing interaction between the x-ray and the sample is the incoherent scattering. The scattered radiation causes a loss of contrast in the results, and its correction has proven to be a complex problem, due to its dependence on energy, material composition, and geometry. Monte Carlo simulations can utilize a physical model to estimate the scattering contribution to the signal, at the cost of high computational time. We present a fast Monte Carlo simulation tool, based on McXtrace, to predict the energy resolved radiation being scattered and absorbed by objects of complex shapes. We validate the tool through measurements using a CdTe single PCD (Multix ME-100) and use it for scattering correction in a simulation of a spectral CT. We found the correction to account for up to 7% relative amplification in the reconstructed linear attenuation. It is a useful tool for x-ray CT to obtain a more accurate material discrimination, especially in the high-energy range, where the incoherent scattering interactions become prevailing (>50 keV).
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WE-AB-207A-07: A Planning CT-Guided Scatter Artifact Correction Method for CBCT Images
DOE Office of Scientific and Technical Information (OSTI.GOV)
Yang, X; Liu, T; Dong, X
Purpose: Cone beam computed tomography (CBCT) imaging is on increasing demand for high-performance image-guided radiotherapy such as online tumor delineation and dose calculation. However, the current CBCT imaging has severe scatter artifacts and its current clinical application is therefore limited to patient setup based mainly on the bony structures. This study’s purpose is to develop a CBCT artifact correction method. Methods: The proposed scatter correction method utilizes the planning CT to improve CBCT image quality. First, an image registration is used to match the planning CT with the CBCT to reduce the geometry difference between the two images. Then, themore » planning CT-based prior information is entered into the Bayesian deconvolution framework to iteratively perform a scatter artifact correction for the CBCT mages. This technique was evaluated using Catphan phantoms with multiple inserts. Contrast-to-noise ratios (CNR) and signal-to-noise ratios (SNR), and the image spatial nonuniformity (ISN) in selected volume of interests (VOIs) were calculated to assess the proposed correction method. Results: Post scatter correction, the CNR increased by a factor of 1.96, 3.22, 3.20, 3.46, 3.44, 1.97 and 1.65, and the SNR increased by a factor 1.05, 2.09, 1.71, 3.95, 2.52, 1.54 and 1.84 for the Air, PMP, LDPE, Polystryrene, Acrylic, Delrin and Teflon inserts, respectively. The ISN decreased from 21.1% to 4.7% in the corrected images. All values of CNR, SNR and ISN in the corrected CBCT image were much closer to those in the planning CT images. The results demonstrated that the proposed method reduces the relevant artifacts and recovers CT numbers. Conclusion: We have developed a novel CBCT artifact correction method based on CT image, and demonstrated that the proposed CT-guided correction method could significantly reduce scatter artifacts and improve the image quality. This method has great potential to correct CBCT images allowing its use in adaptive radiotherapy.« less
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Müller, I; Kordowich, S; Holzwarth, C; Spano, C; Isensee, G; Staiber, A; Viebahn, S; Gieseke, F; Langer, H; Gawaz, M P; Horwitz, E M; Conte, P; Handgretinger, R; Dominici, M
2006-01-01
Multipotent mesenchymal stromal cells (MSC) have become important tools in regenerative and transplantation medicine. Rapidly increasing numbers of patients are receiving in vitro-expanded MSC. Culture conditions typically include FSC because human serum does not fully support growth of human MSC in vitro (MSC(FCS)). Concerns regarding BSE, other infectious complications and host immune reactions have fueled investigation of alternative culture supplements. As PDGF has long been identified as a growth factor for MSC, we tested media supplementation with platelet lysate for support of MSC proliferation. We found that primary cultures of BM-derived MSC can be established with animal serum-free media containing fresh frozen plasma and platelets (MSC(FFPP)). Moreover, MSC(FFPP) showed vigorous proliferation that was superior to classical culture conditions containing FCS. MSC(FFPP) morphology was equivalent to MSC(FCS), and MSC(FFPP) expressed CD73, CD90, CD105, CD106, CD146 and HLA-ABC while being negative for CD34, CD45 and surface HLA-DR, as expected. In addition to being phenotypically identical, MSC(FFPP) could efficiently differentiate into adipocytes and osteoblasts. In terms of immune regulatory properties, MSC(FFPP) were indistinguishable from MSC(FCS). Proliferation of PBMC induced by IL-2 in combination with OKT-3 or by PHA was inhibited in the presence of MSC(FFPP). Taken together, FCS can be replaced safely by FFPP in cultures of MSC for clinical purposes.
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ERIC Educational Resources Information Center
Young, Andrew T.
1982-01-01
The correct usage of such terminology as "Rayleigh scattering,""Rayleigh lines,""Raman lines," and "Tyndall scattering" is resolved during an historical excursion through the physics of light-scattering by gas molecules. (Author/JN)
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Guide-star-based computational adaptive optics for broadband interferometric tomography
Adie, Steven G.; Shemonski, Nathan D.; Graf, Benedikt W.; Ahmad, Adeel; Scott Carney, P.; Boppart, Stephen A.
2012-01-01
We present a method for the numerical correction of optical aberrations based on indirect sensing of the scattered wavefront from point-like scatterers (“guide stars”) within a three-dimensional broadband interferometric tomogram. This method enables the correction of high-order monochromatic and chromatic aberrations utilizing guide stars that are revealed after numerical compensation of defocus and low-order aberrations of the optical system. Guide-star-based aberration correction in a silicone phantom with sparse sub-resolution-sized scatterers demonstrates improvement of resolution and signal-to-noise ratio over a large isotome. Results in highly scattering muscle tissue showed improved resolution of fine structure over an extended volume. Guide-star-based computational adaptive optics expands upon the use of image metrics for numerically optimizing the aberration correction in broadband interferometric tomography, and is analogous to phase-conjugation and time-reversal methods for focusing in turbid media. PMID:23284179
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Investigation of the halo-artifact in 68Ga-PSMA-11-PET/MRI.
Heußer, Thorsten; Mann, Philipp; Rank, Christopher M; Schäfer, Martin; Dimitrakopoulou-Strauss, Antonia; Schlemmer, Heinz-Peter; Hadaschik, Boris A; Kopka, Klaus; Bachert, Peter; Kachelrieß, Marc; Freitag, Martin T
2017-01-01
Combined positron emission tomography (PET) and magnetic resonance imaging (MRI) targeting the prostate-specific membrane antigen (PSMA) with a 68Ga-labelled PSMA-analog (68Ga-PSMA-11) is discussed as a promising diagnostic method for patients with suspicion or history of prostate cancer. One potential drawback of this method are severe photopenic (halo-) artifacts surrounding the bladder and the kidneys in the scatter-corrected PET images, which have been reported to occur frequently in clinical practice. The goal of this work was to investigate the occurrence and impact of these artifacts and, secondly, to evaluate variants of the standard scatter correction method with regard to halo-artifact suppression. Experiments using a dedicated pelvis phantom were conducted to investigate whether the halo-artifact is modality-, tracer-, and/or concentration-dependent. Furthermore, 31 patients with history of prostate cancer were selected from an ongoing 68Ga-PSMA-11-PET/MRI study. For each patient, PET raw data were reconstructed employing six different variants of PET scatter correction: absolute scatter scaling, relative scatter scaling, and relative scatter scaling combined with prompt gamma correction, each of which was combined with a maximum scatter fraction (MaxSF) of MaxSF = 75% or MaxSF = 40%. Evaluation of the reconstructed images with regard to halo-artifact suppression was performed both quantitatively using statistical analysis and qualitatively by two independent readers. The phantom experiments did not reveal any modality-dependency (PET/MRI vs. PET/CT) or tracer-dependency (68Ga vs. 18F-FDG). Patient- and phantom-based data indicated that halo-artifacts derive from high organ-to-background activity ratios (OBR) between bladder/kidneys and surrounding soft tissue, with a positive correlation between OBR and halo size. Comparing different variants of scatter correction, reducing the maximum scatter fraction from the default value MaxSF = 75% to MaxSF = 40% was found to efficiently suppress halo-artifacts in both phantom and patient data. In 1 of 31 patients, reducing the maximum scatter fraction provided new PET-based information changing the patient's diagnosis. Halo-artifacts are particularly observed for 68Ga-PSMA-11-PET/MRI due to 1) the biodistribution of the PSMA-11-tracer resulting in large OBRs for bladder and kidneys and 2) inaccurate scatter correction methods currently used in clinical routine, which tend to overestimate the scatter contribution. If not compensated for, 68Ga-PSMA-11 uptake pathologies may be masked by halo-artifacts leading to false-negative diagnoses. Reducing the maximum scatter fraction was found to efficiently suppress halo-artifacts.
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Investigation of the halo-artifact in 68Ga-PSMA-11-PET/MRI
Rank, Christopher M.; Schäfer, Martin; Dimitrakopoulou-Strauss, Antonia; Schlemmer, Heinz-Peter; Hadaschik, Boris A.; Kopka, Klaus; Bachert, Peter; Kachelrieß, Marc
2017-01-01
Objectives Combined positron emission tomography (PET) and magnetic resonance imaging (MRI) targeting the prostate-specific membrane antigen (PSMA) with a 68Ga-labelled PSMA-analog (68Ga-PSMA-11) is discussed as a promising diagnostic method for patients with suspicion or history of prostate cancer. One potential drawback of this method are severe photopenic (halo-) artifacts surrounding the bladder and the kidneys in the scatter-corrected PET images, which have been reported to occur frequently in clinical practice. The goal of this work was to investigate the occurrence and impact of these artifacts and, secondly, to evaluate variants of the standard scatter correction method with regard to halo-artifact suppression. Methods Experiments using a dedicated pelvis phantom were conducted to investigate whether the halo-artifact is modality-, tracer-, and/or concentration-dependent. Furthermore, 31 patients with history of prostate cancer were selected from an ongoing 68Ga-PSMA-11-PET/MRI study. For each patient, PET raw data were reconstructed employing six different variants of PET scatter correction: absolute scatter scaling, relative scatter scaling, and relative scatter scaling combined with prompt gamma correction, each of which was combined with a maximum scatter fraction (MaxSF) of MaxSF = 75% or MaxSF = 40%. Evaluation of the reconstructed images with regard to halo-artifact suppression was performed both quantitatively using statistical analysis and qualitatively by two independent readers. Results The phantom experiments did not reveal any modality-dependency (PET/MRI vs. PET/CT) or tracer-dependency (68Ga vs. 18F-FDG). Patient- and phantom-based data indicated that halo-artifacts derive from high organ-to-background activity ratios (OBR) between bladder/kidneys and surrounding soft tissue, with a positive correlation between OBR and halo size. Comparing different variants of scatter correction, reducing the maximum scatter fraction from the default value MaxSF = 75% to MaxSF = 40% was found to efficiently suppress halo-artifacts in both phantom and patient data. In 1 of 31 patients, reducing the maximum scatter fraction provided new PET-based information changing the patient’s diagnosis. Conclusion Halo-artifacts are particularly observed for 68Ga-PSMA-11-PET/MRI due to 1) the biodistribution of the PSMA-11-tracer resulting in large OBRs for bladder and kidneys and 2) inaccurate scatter correction methods currently used in clinical routine, which tend to overestimate the scatter contribution. If not compensated for, 68Ga-PSMA-11 uptake pathologies may be masked by halo-artifacts leading to false-negative diagnoses. Reducing the maximum scatter fraction was found to efficiently suppress halo-artifacts. PMID:28817656
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Ahn, Jae-Hyun; Park, Young-Je; Kim, Wonkook; Lee, Boram
2016-12-26
An estimation of the aerosol multiple-scattering reflectance is an important part of the atmospheric correction procedure in satellite ocean color data processing. Most commonly, the utilization of two near-infrared (NIR) bands to estimate the aerosol optical properties has been adopted for the estimation of the effects of aerosols. Previously, the operational Geostationary Color Ocean Imager (GOCI) atmospheric correction scheme relies on a single-scattering reflectance ratio (SSE), which was developed for the processing of the Sea-viewing Wide Field-of-view Sensor (SeaWiFS) data to determine the appropriate aerosol models and their aerosol optical thicknesses. The scheme computes reflectance contributions (weighting factor) of candidate aerosol models in a single scattering domain then spectrally extrapolates the single-scattering aerosol reflectance from NIR to visible (VIS) bands using the SSE. However, it directly applies the weight value to all wavelengths in a multiple-scattering domain although the multiple-scattering aerosol reflectance has a non-linear relationship with the single-scattering reflectance and inter-band relationship of multiple scattering aerosol reflectances is non-linear. To avoid these issues, we propose an alternative scheme for estimating the aerosol reflectance that uses the spectral relationships in the aerosol multiple-scattering reflectance between different wavelengths (called SRAMS). The process directly calculates the multiple-scattering reflectance contributions in NIR with no residual errors for selected aerosol models. Then it spectrally extrapolates the reflectance contribution from NIR to visible bands for each selected model using the SRAMS. To assess the performance of the algorithm regarding the errors in the water reflectance at the surface or remote-sensing reflectance retrieval, we compared the SRAMS atmospheric correction results with the SSE atmospheric correction using both simulations and in situ match-ups with the GOCI data. From simulations, the mean errors for bands from 412 to 555 nm were 5.2% for the SRAMS scheme and 11.5% for SSE scheme in case-I waters. From in situ match-ups, 16.5% for the SRAMS scheme and 17.6% scheme for the SSE scheme in both case-I and case-II waters. Although we applied the SRAMS algorithm to the GOCI, it can be applied to other ocean color sensors which have two NIR wavelengths.
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TH-A-18C-09: Ultra-Fast Monte Carlo Simulation for Cone Beam CT Imaging of Brain Trauma
DOE Office of Scientific and Technical Information (OSTI.GOV)
Sisniega, A; Zbijewski, W; Stayman, J
Purpose: Application of cone-beam CT (CBCT) to low-contrast soft tissue imaging, such as in detection of traumatic brain injury, is challenged by high levels of scatter. A fast, accurate scatter correction method based on Monte Carlo (MC) estimation is developed for application in high-quality CBCT imaging of acute brain injury. Methods: The correction involves MC scatter estimation executed on an NVIDIA GTX 780 GPU (MC-GPU), with baseline simulation speed of ~1e7 photons/sec. MC-GPU is accelerated by a novel, GPU-optimized implementation of variance reduction (VR) techniques (forced detection and photon splitting). The number of simulated tracks and projections is reduced formore » additional speed-up. Residual noise is removed and the missing scatter projections are estimated via kernel smoothing (KS) in projection plane and across gantry angles. The method is assessed using CBCT images of a head phantom presenting a realistic simulation of fresh intracranial hemorrhage (100 kVp, 180 mAs, 720 projections, source-detector distance 700 mm, source-axis distance 480 mm). Results: For a fixed run-time of ~1 sec/projection, GPU-optimized VR reduces the noise in MC-GPU scatter estimates by a factor of 4. For scatter correction, MC-GPU with VR is executed with 4-fold angular downsampling and 1e5 photons/projection, yielding 3.5 minute run-time per scan, and de-noised with optimized KS. Corrected CBCT images demonstrate uniformity improvement of 18 HU and contrast improvement of 26 HU compared to no correction, and a 52% increase in contrast-tonoise ratio in simulated hemorrhage compared to “oracle” constant fraction correction. Conclusion: Acceleration of MC-GPU achieved through GPU-optimized variance reduction and kernel smoothing yields an efficient (<5 min/scan) and accurate scatter correction that does not rely on additional hardware or simplifying assumptions about the scatter distribution. The method is undergoing implementation in a novel CBCT dedicated to brain trauma imaging at the point of care in sports and military applications. Research grant from Carestream Health. JY is an employee of Carestream Health.« less
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NASA Astrophysics Data System (ADS)
Gillen, Rebecca; Firbank, Michael J.; Lloyd, Jim; O'Brien, John T.
2015-09-01
This study investigated if the appearance and diagnostic accuracy of HMPAO brain perfusion SPECT images could be improved by using CT-based attenuation and scatter correction compared with the uniform attenuation correction method. A cohort of subjects who were clinically categorized as Alzheimer’s Disease (n=38 ), Dementia with Lewy Bodies (n=29 ) or healthy normal controls (n=30 ), underwent SPECT imaging with Tc-99m HMPAO and a separate CT scan. The SPECT images were processed using: (a) correction map derived from the subject’s CT scan or (b) the Chang uniform approximation for correction or (c) no attenuation correction. Images were visually inspected. The ratios between key regions of interest known to be affected or spared in each condition were calculated for each correction method, and the differences between these ratios were evaluated. The images produced using the different corrections were noted to be visually different. However, ROI analysis found similar statistically significant differences between control and dementia groups and between AD and DLB groups regardless of the correction map used. We did not identify an improvement in diagnostic accuracy in images which were corrected using CT-based attenuation and scatter correction, compared with those corrected using a uniform correction map.
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Scatter correction for x-ray conebeam CT using one-dimensional primary modulation
NASA Astrophysics Data System (ADS)
Zhu, Lei; Gao, Hewei; Bennett, N. Robert; Xing, Lei; Fahrig, Rebecca
2009-02-01
Recently, we developed an efficient scatter correction method for x-ray imaging using primary modulation. A two-dimensional (2D) primary modulator with spatially variant attenuating materials is inserted between the x-ray source and the object to separate primary and scatter signals in the Fourier domain. Due to the high modulation frequency in both directions, the 2D primary modulator has a strong scatter correction capability for objects with arbitrary geometries. However, signal processing on the modulated projection data requires knowledge of the modulator position and attenuation. In practical systems, mainly due to system gantry vibration, beam hardening effects and the ramp-filtering in the reconstruction, the insertion of the 2D primary modulator results in artifacts such as rings in the CT images, if no post-processing is applied. In this work, we eliminate the source of artifacts in the primary modulation method by using a one-dimensional (1D) modulator. The modulator is aligned parallel to the ramp-filtering direction to avoid error magnification, while sufficient primary modulation is still achieved for scatter correction on a quasicylindrical object, such as a human body. The scatter correction algorithm is also greatly simplified for the convenience and stability in practical implementations. The method is evaluated on a clinical CBCT system using the Catphan© 600 phantom. The result shows effective scatter suppression without introducing additional artifacts. In the selected regions of interest, the reconstruction error is reduced from 187.2HU to 10.0HU if the proposed method is used.
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Improved scatter correction using adaptive scatter kernel superposition
NASA Astrophysics Data System (ADS)
Sun, M.; Star-Lack, J. M.
2010-11-01
Accurate scatter correction is required to produce high-quality reconstructions of x-ray cone-beam computed tomography (CBCT) scans. This paper describes new scatter kernel superposition (SKS) algorithms for deconvolving scatter from projection data. The algorithms are designed to improve upon the conventional approach whose accuracy is limited by the use of symmetric kernels that characterize the scatter properties of uniform slabs. To model scatter transport in more realistic objects, nonstationary kernels, whose shapes adapt to local thickness variations in the projection data, are proposed. Two methods are introduced: (1) adaptive scatter kernel superposition (ASKS) requiring spatial domain convolutions and (2) fast adaptive scatter kernel superposition (fASKS) where, through a linearity approximation, convolution is efficiently performed in Fourier space. The conventional SKS algorithm, ASKS, and fASKS, were tested with Monte Carlo simulations and with phantom data acquired on a table-top CBCT system matching the Varian On-Board Imager (OBI). All three models accounted for scatter point-spread broadening due to object thickening, object edge effects, detector scatter properties and an anti-scatter grid. Hounsfield unit (HU) errors in reconstructions of a large pelvis phantom with a measured maximum scatter-to-primary ratio over 200% were reduced from -90 ± 58 HU (mean ± standard deviation) with no scatter correction to 53 ± 82 HU with SKS, to 19 ± 25 HU with fASKS and to 13 ± 21 HU with ASKS. HU accuracies and measured contrast were similarly improved in reconstructions of a body-sized elliptical Catphan phantom. The results show that the adaptive SKS methods offer significant advantages over the conventional scatter deconvolution technique.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Ouyang, L; Lee, H; Wang, J
2014-06-01
Purpose: To evaluate a moving-blocker-based approach in estimating and correcting megavoltage (MV) and kilovoltage (kV) scatter contamination in kV cone-beam computed tomography (CBCT) acquired during volumetric modulated arc therapy (VMAT). Methods: XML code was generated to enable concurrent CBCT acquisition and VMAT delivery in Varian TrueBeam developer mode. A physical attenuator (i.e., “blocker”) consisting of equal spaced lead strips (3.2mm strip width and 3.2mm gap in between) was mounted between the x-ray source and patient at a source to blocker distance of 232mm. The blocker was simulated to be moving back and forth along the gantry rotation axis during themore » CBCT acquisition. Both MV and kV scatter signal were estimated simultaneously from the blocked regions of the imaging panel, and interpolated into the un-blocked regions. Scatter corrected CBCT was then reconstructed from un-blocked projections after scatter subtraction using an iterative image reconstruction algorithm based on constraint optimization. Experimental studies were performed on a Catphan 600 phantom and an anthropomorphic pelvis phantom to demonstrate the feasibility of using moving blocker for MV-kV scatter correction. Results: MV scatter greatly degrades the CBCT image quality by increasing the CT number inaccuracy and decreasing the image contrast, in addition to the shading artifacts caused by kV scatter. The artifacts were substantially reduced in the moving blocker corrected CBCT images in both Catphan and pelvis phantoms. Quantitatively, CT number error in selected regions of interest reduced from 377 in the kV-MV contaminated CBCT image to 38 for the Catphan phantom. Conclusions: The moving-blockerbased strategy can successfully correct MV and kV scatter simultaneously in CBCT projection data acquired with concurrent VMAT delivery. This work was supported in part by a grant from the Cancer Prevention and Research Institute of Texas (RP130109) and a grant from the American Cancer Society (RSG-13-326-01-CCE)« less
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Min, Jonghwan; Pua, Rizza; Cho, Seungryong, E-mail: scho@kaist.ac.kr
Purpose: A beam-blocker composed of multiple strips is a useful gadget for scatter correction and/or for dose reduction in cone-beam CT (CBCT). However, the use of such a beam-blocker would yield cone-beam data that can be challenging for accurate image reconstruction from a single scan in the filtered-backprojection framework. The focus of the work was to develop an analytic image reconstruction method for CBCT that can be directly applied to partially blocked cone-beam data in conjunction with the scatter correction. Methods: The authors developed a rebinned backprojection-filteration (BPF) algorithm for reconstructing images from the partially blocked cone-beam data in amore » circular scan. The authors also proposed a beam-blocking geometry considering data redundancy such that an efficient scatter estimate can be acquired and sufficient data for BPF image reconstruction can be secured at the same time from a single scan without using any blocker motion. Additionally, scatter correction method and noise reduction scheme have been developed. The authors have performed both simulation and experimental studies to validate the rebinned BPF algorithm for image reconstruction from partially blocked cone-beam data. Quantitative evaluations of the reconstructed image quality were performed in the experimental studies. Results: The simulation study revealed that the developed reconstruction algorithm successfully reconstructs the images from the partial cone-beam data. In the experimental study, the proposed method effectively corrected for the scatter in each projection and reconstructed scatter-corrected images from a single scan. Reduction of cupping artifacts and an enhancement of the image contrast have been demonstrated. The image contrast has increased by a factor of about 2, and the image accuracy in terms of root-mean-square-error with respect to the fan-beam CT image has increased by more than 30%. Conclusions: The authors have successfully demonstrated that the proposed scanning method and image reconstruction algorithm can effectively estimate the scatter in cone-beam projections and produce tomographic images of nearly scatter-free quality. The authors believe that the proposed method would provide a fast and efficient CBCT scanning option to various applications particularly including head-and-neck scan.« less
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Correction of Rayleigh Scattering Effects in Cloud Optical Thickness Retrievals
NASA Technical Reports Server (NTRS)
Wang, Meng-Hua; King, Michael D.
1997-01-01
We present results that demonstrate the effects of Rayleigh scattering on the 9 retrieval of cloud optical thickness at a visible wavelength (0.66 Am). The sensor-measured radiance at a visible wavelength (0.66 Am) is usually used to infer remotely the cloud optical thickness from aircraft or satellite instruments. For example, we find that without removing Rayleigh scattering effects, errors in the retrieved cloud optical thickness for a thin water cloud layer (T = 2.0) range from 15 to 60%, depending on solar zenith angle and viewing geometry. For an optically thick cloud (T = 10), on the other hand, errors can range from 10 to 60% for large solar zenith angles (0-60 deg) because of enhanced Rayleigh scattering. It is therefore particularly important to correct for Rayleigh scattering contributions to the reflected signal from a cloud layer both (1) for the case of thin clouds and (2) for large solar zenith angles and all clouds. On the basis of the single scattering approximation, we propose an iterative method for effectively removing Rayleigh scattering contributions from the measured radiance signal in cloud optical thickness retrievals. The proposed correction algorithm works very well and can easily be incorporated into any cloud retrieval algorithm. The Rayleigh correction method is applicable to cloud at any pressure, providing that the cloud top pressure is known to within +/- 100 bPa. With the Rayleigh correction the errors in retrieved cloud optical thickness are usually reduced to within 3%. In cases of both thin cloud layers and thick ,clouds with large solar zenith angles, the errors are usually reduced by a factor of about 2 to over 10. The Rayleigh correction algorithm has been tested with simulations for realistic cloud optical and microphysical properties with different solar and viewing geometries. We apply the Rayleigh correction algorithm to the cloud optical thickness retrievals from experimental data obtained during the Atlantic Stratocumulus Transition Experiment (ASTEX) conducted near the Azores in June 1992 and compare these results to corresponding retrievals obtained using 0.88 Am. These results provide an example of the Rayleigh scattering effects on thin clouds and further test the Rayleigh correction scheme. Using a nonabsorbing near-infrared wavelength lambda (0.88 Am) in retrieving cloud optical thickness is only applicable over oceans, however, since most land surfaces are highly reflective at 0.88 Am. Hence successful global retrievals of cloud optical thickness should remove Rayleigh scattering effects when using reflectance measurements at 0.66 Am.
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NASA Astrophysics Data System (ADS)
Wozniak, Kaitlin T.; Germer, Thomas A.; Butler, Sam C.; Brooks, Daniel R.; Huxlin, Krystel R.; Ellis, Jonathan D.
2018-02-01
We present measurements of light scatter induced by a new ultrafast laser technique being developed for laser refractive correction in transparent ophthalmic materials such as cornea, contact lenses, and/or intraocular lenses. In this new technique, called intra-tissue refractive index shaping (IRIS), a 405 nm femtosecond laser is focused and scanned below the corneal surface, inducing a spatially-varying refractive index change that corrects vision errors. In contrast with traditional laser correction techniques, such as laser in-situ keratomileusis (LASIK) or photorefractive keratectomy (PRK), IRIS does not operate via photoablation, but rather changes the refractive index of transparent materials such as cornea and hydrogels. A concern with any laser eye correction technique is additional scatter induced by the process, which can adversely affect vision, especially at night. The goal of this investigation is to identify sources of scatter induced by IRIS and to mitigate possible effects on visual performance in ophthalmic applications. Preliminary light scattering measurements on patterns written into hydrogel showed four sources of scatter, differentiated by distinct behaviors: (1) scattering from scanned lines; (2) scattering from stitching errors, resulting from adjacent scanning fields not being aligned to one another; (3) diffraction from Fresnel zone discontinuities; and (4) long-period variations in the scans that created distinct diffraction peaks, likely due to inconsistent line spacing in the writing instrument. By knowing the nature of these different scattering errors, it will now be possible to modify and optimize the design of IRIS structures to mitigate potential deficits in visual performance in human clinical trials.
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Rayleigh, Compton and K-shell radiative resonant Raman scattering in 83Bi for 88.034 keV γ-rays
NASA Astrophysics Data System (ADS)
Kumar, Sanjeev; Sharma, Veena; Mehta, D.; Singh, Nirmal
2007-11-01
The Rayleigh, Compton and K-shell radiative resonant Raman scattering cross-sections for the 88.034 keV γ-rays have been measured in the 83Bi (K-shell binding energy = 90.526 keV) element. The measurements have been performed at 130° scattering angle using reflection-mode geometrical arrangement involving the 109Cd radioisotope as photon source and an LEGe detector. Computer simulations were exercised to determine distributions of the incident and emission angles, which were further used in evaluation of the absorption corrections for the incident and emitted photons in the target. The measured cross-sections for the Rayleigh scattering are compared with the modified form-factors (MFs) corrected for the anomalous-scattering factors (ASFs) and the S-matrix calculations; and those for the Compton scattering are compared with the Klein-Nishina cross-sections corrected for the non-relativistic Hartree-Fock incoherent scattering function S(x, Z). The ratios of the measured KL2, KL3, KM and KN2,3 radiative resonant Raman scattering cross-sections are found to be in general agreement with those of the corresponding measured fluorescence transition probabilities.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Prior, P; Timmins, R; Wells, R G
Dual isotope SPECT allows simultaneous measurement of two different tracers in vivo. With In111 (emission energies of 171keV and 245keV) and Tc99m (140keV), quantification of Tc99m is degraded by cross talk from the In111 photons that scatter and are detected at an energy corresponding to Tc99m. TEW uses counts recorded in two narrow windows surrounding the Tc99m primary window to estimate scatter. Iterative TEW corrects for the bias introduced into the TEW estimate resulting from un-scattered counts detected in the scatter windows. The contamination in the scatter windows is iteratively estimated and subtracted as a fraction of the scatter-corrected primarymore » window counts. The iterative TEW approach was validated with a small-animal SPECT/CT camera using a 2.5mL plastic container holding thoroughly mixed Tc99m/In111 activity fractions of 0.15, 0.28, 0.52, 0.99, 2.47 and 6.90. Dose calibrator measurements were the gold standard. Uncorrected for scatter, the Tc99m activity was over-estimated by as much as 80%. Unmodified TEW underestimated the Tc99m activity by 13%. With iterative TEW corrections applied in projection space, the Tc99m activity was estimated within 5% of truth across all activity fractions above 0.15. This is an improvement over the non-iterative TEW, which could not sufficiently correct for scatter in the 0.15 and 0.28 phantoms.« less
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Library based x-ray scatter correction for dedicated cone beam breast CT
Shi, Linxi; Karellas, Andrew; Zhu, Lei
2016-01-01
Purpose: The image quality of dedicated cone beam breast CT (CBBCT) is limited by substantial scatter contamination, resulting in cupping artifacts and contrast-loss in reconstructed images. Such effects obscure the visibility of soft-tissue lesions and calcifications, which hinders breast cancer detection and diagnosis. In this work, we propose a library-based software approach to suppress scatter on CBBCT images with high efficiency, accuracy, and reliability. Methods: The authors precompute a scatter library on simplified breast models with different sizes using the geant4-based Monte Carlo (MC) toolkit. The breast is approximated as a semiellipsoid with homogeneous glandular/adipose tissue mixture. For scatter correction on real clinical data, the authors estimate the breast size from a first-pass breast CT reconstruction and then select the corresponding scatter distribution from the library. The selected scatter distribution from simplified breast models is spatially translated to match the projection data from the clinical scan and is subtracted from the measured projection for effective scatter correction. The method performance was evaluated using 15 sets of patient data, with a wide range of breast sizes representing about 95% of general population. Spatial nonuniformity (SNU) and contrast to signal deviation ratio (CDR) were used as metrics for evaluation. Results: Since the time-consuming MC simulation for library generation is precomputed, the authors’ method efficiently corrects for scatter with minimal processing time. Furthermore, the authors find that a scatter library on a simple breast model with only one input parameter, i.e., the breast diameter, sufficiently guarantees improvements in SNU and CDR. For the 15 clinical datasets, the authors’ method reduces the average SNU from 7.14% to 2.47% in coronal views and from 10.14% to 3.02% in sagittal views. On average, the CDR is improved by a factor of 1.49 in coronal views and 2.12 in sagittal views. Conclusions: The library-based scatter correction does not require increase in radiation dose or hardware modifications, and it improves over the existing methods on implementation simplicity and computational efficiency. As demonstrated through patient studies, the authors’ approach is effective and stable, and is therefore clinically attractive for CBBCT imaging. PMID:27487870
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Higher Order Heavy Quark Corrections to Deep-Inelastic Scattering
NASA Astrophysics Data System (ADS)
Blümlein, Johannes; DeFreitas, Abilio; Schneider, Carsten
2015-04-01
The 3-loop heavy flavor corrections to deep-inelastic scattering are essential for consistent next-to-next-to-leading order QCD analyses. We report on the present status of the calculation of these corrections at large virtualities Q2. We also describe a series of mathematical, computer-algebraic and combinatorial methods and special function spaces, needed to perform these calculations. Finally, we briefly discuss the status of measuring αs (MZ), the charm quark mass mc, and the parton distribution functions at next-to-next-to-leading order from the world precision data on deep-inelastic scattering.
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Lee, Ho; Fahimian, Benjamin P; Xing, Lei
2017-03-21
This paper proposes a binary moving-blocker (BMB)-based technique for scatter correction in cone-beam computed tomography (CBCT). In concept, a beam blocker consisting of lead strips, mounted in front of the x-ray tube, moves rapidly in and out of the beam during a single gantry rotation. The projections are acquired in alternating phases of blocked and unblocked cone beams, where the blocked phase results in a stripe pattern in the width direction. To derive the scatter map from the blocked projections, 1D B-Spline interpolation/extrapolation is applied by using the detected information in the shaded regions. The scatter map of the unblocked projections is corrected by averaging two scatter maps that correspond to their adjacent blocked projections. The scatter-corrected projections are obtained by subtracting the corresponding scatter maps from the projection data and are utilized to generate the CBCT image by a compressed-sensing (CS)-based iterative reconstruction algorithm. Catphan504 and pelvis phantoms were used to evaluate the method's performance. The proposed BMB-based technique provided an effective method to enhance the image quality by suppressing scatter-induced artifacts, such as ring artifacts around the bowtie area. Compared to CBCT without a blocker, the spatial nonuniformity was reduced from 9.1% to 3.1%. The root-mean-square error of the CT numbers in the regions of interest (ROIs) was reduced from 30.2 HU to 3.8 HU. In addition to high resolution, comparable to that of the benchmark image, the CS-based reconstruction also led to a better contrast-to-noise ratio in seven ROIs. The proposed technique enables complete scatter-corrected CBCT imaging with width-truncated projections and allows reducing the acquisition time to approximately half. This work may have significant implications for image-guided or adaptive radiation therapy, where CBCT is often used.
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NASA Astrophysics Data System (ADS)
Lee, Ho; Fahimian, Benjamin P.; Xing, Lei
2017-03-01
This paper proposes a binary moving-blocker (BMB)-based technique for scatter correction in cone-beam computed tomography (CBCT). In concept, a beam blocker consisting of lead strips, mounted in front of the x-ray tube, moves rapidly in and out of the beam during a single gantry rotation. The projections are acquired in alternating phases of blocked and unblocked cone beams, where the blocked phase results in a stripe pattern in the width direction. To derive the scatter map from the blocked projections, 1D B-Spline interpolation/extrapolation is applied by using the detected information in the shaded regions. The scatter map of the unblocked projections is corrected by averaging two scatter maps that correspond to their adjacent blocked projections. The scatter-corrected projections are obtained by subtracting the corresponding scatter maps from the projection data and are utilized to generate the CBCT image by a compressed-sensing (CS)-based iterative reconstruction algorithm. Catphan504 and pelvis phantoms were used to evaluate the method’s performance. The proposed BMB-based technique provided an effective method to enhance the image quality by suppressing scatter-induced artifacts, such as ring artifacts around the bowtie area. Compared to CBCT without a blocker, the spatial nonuniformity was reduced from 9.1% to 3.1%. The root-mean-square error of the CT numbers in the regions of interest (ROIs) was reduced from 30.2 HU to 3.8 HU. In addition to high resolution, comparable to that of the benchmark image, the CS-based reconstruction also led to a better contrast-to-noise ratio in seven ROIs. The proposed technique enables complete scatter-corrected CBCT imaging with width-truncated projections and allows reducing the acquisition time to approximately half. This work may have significant implications for image-guided or adaptive radiation therapy, where CBCT is often used.
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Scatter correction method for x-ray CT using primary modulation: Phantom studies
Gao, Hewei; Fahrig, Rebecca; Bennett, N. Robert; Sun, Mingshan; Star-Lack, Josh; Zhu, Lei
2010-01-01
Purpose: Scatter correction is a major challenge in x-ray imaging using large area detectors. Recently, the authors proposed a promising scatter correction method for x-ray computed tomography (CT) using primary modulation. Proof of concept was previously illustrated by Monte Carlo simulations and physical experiments on a small phantom with a simple geometry. In this work, the authors provide a quantitative evaluation of the primary modulation technique and demonstrate its performance in applications where scatter correction is more challenging. Methods: The authors first analyze the potential errors of the estimated scatter in the primary modulation method. On two tabletop CT systems, the method is investigated using three phantoms: A Catphan©600 phantom, an anthropomorphic chest phantom, and the Catphan©600 phantom with two annuli. Two different primary modulators are also designed to show the impact of the modulator parameters on the scatter correction efficiency. The first is an aluminum modulator with a weak modulation and a low modulation frequency, and the second is a copper modulator with a strong modulation and a high modulation frequency. Results: On the Catphan©600 phantom in the first study, the method reduces the error of the CT number in the selected regions of interest (ROIs) from 371.4 to 21.9 Hounsfield units (HU); the contrast to noise ratio also increases from 10.9 to 19.2. On the anthropomorphic chest phantom in the second study, which represents a more difficult case due to the high scatter signals and object heterogeneity, the method reduces the error of the CT number from 327 to 19 HU in the selected ROIs and from 31.4% to 5.7% on the overall average. The third study is to investigate the impact of object size on the efficiency of our method. The scatter-to-primary ratio estimation error on the Catphan©600 phantom without any annulus (20 cm in diameter) is at the level of 0.04, it rises to 0.07 and 0.1 on the phantom with an elliptical annulus (30 cm in the minor axis and 38 cm in the major axis) and with a circular annulus (38 cm in diameter). Conclusions: On the three phantom studies, good scatter correction performance of the proposed method has been demonstrated using both image comparisons and quantitative analysis. The theory and experiments demonstrate that a strong primary modulation that possesses a low transmission factor and a high modulation frequency is preferred for high scatter correction accuracy. PMID:20229902
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Characterization and correction of cupping effect artefacts in cone beam CT
Hunter, AK; McDavid, WD
2012-01-01
Objective The purpose of this study was to demonstrate and correct the cupping effect artefact that occurs owing to the presence of beam hardening and scatter radiation during image acquisition in cone beam CT (CBCT). Methods A uniform aluminium cylinder (6061) was used to demonstrate the cupping effect artefact on the Planmeca Promax 3D CBCT unit (Planmeca OY, Helsinki, Finland). The cupping effect was studied using a line profile plot of the grey level values using ImageJ software (National Institutes of Health, Bethesda, MD). A hardware-based correction method using copper pre-filtration was used to address this artefact caused by beam hardening and a software-based subtraction algorithm was used to address scatter contamination. Results The hardware-based correction used to address the effects of beam hardening suppressed the cupping effect artefact but did not eliminate it. The software-based correction used to address the effects of scatter resulted in elimination of the cupping effect artefact. Conclusion Compensating for the presence of beam hardening and scatter radiation improves grey level uniformity in CBCT. PMID:22378754
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NASA Astrophysics Data System (ADS)
Zhai, Peng-Wang; Hu, Yongxiang; Josset, Damien B.; Trepte, Charles R.; Lucker, Patricia L.; Lin, Bing
2012-06-01
We have developed a Vector Radiative Transfer (VRT) code for coupled atmosphere and ocean systems based on the successive order of scattering (SOS) method. In order to achieve efficiency and maintain accuracy, the scattering matrix is expanded in terms of the Wigner d functions and the delta fit or delta-M technique is used to truncate the commonly-present large forward scattering peak. To further improve the accuracy of the SOS code, we have implemented the analytical first order scattering treatment using the exact scattering matrix of the medium in the SOS code. The expansion and truncation techniques are kept for higher order scattering. The exact first order scattering correction was originally published by Nakajima and Takana.1 A new contribution of this work is to account for the exact secondary light scattering caused by the light reflected by and transmitted through the rough air-sea interface.
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Ezzelarab, Mohamed; Ezzelarab, Corin; Wilhite, Tyler; Kumar, Goutham; Hara, Hidetaka; Ayares, David; Cooper, David K C
2011-01-01
Mesenchymal stromal cells (MSC) are being investigated as immunomodulatory therapy in the field of transplantation, particularly islet transplantation. While MSC can regenerate across species barriers, the immunoregulatory influence of genetically modified pig MSC (pMSC) on the human and non-human primate T-cell responses has not been studied. Mesenchymal stromal cells from wild-type (WT), α1,3-galactosyltransferase gene knockout (GTKO) and GTKO pigs transgenic for the human complement-regulatory protein CD46 (GTKO/CD46) were isolated and tested for differentiation. Antibody binding and T-cell responses to WT and GTKO pMSC in comparison with GTKO pig aortic endothelial cells (pAEC) were investigated. The expression of swine leukocyte antigen (SLA) class II (SLA II) was tested. Costimulatory molecules CD80 and CD86 mRNA levels were measured. Human T-cell proliferation and the production of pro-inflammatory cytokines in response to GTKO and GTKO/CD46 pMSC in comparison with human MSC (hMSC) were evaluated. α1,3-galactosyltransferase gene knockout and GTKO/CD46 pMSC isolation and differentiation were achieved in vitro. Binding of human antibodies and T-cell responses were lower to GTKO than those to WT pMSC. Human and baboon (naïve and sensitized) antibody binding were significantly lower to GTKO pMSC than to GTKO pAEC. Before activation, <1% of GTKO pMSC expressed SLA II, compared with 2.5% of GTKO pAEC. After pig interferon-gamma (pIFN-γ) activation, 99% of GTKO pAEC upregulated SLA II expression, compared with 49% of GTKO pMSC. Only 3% of GTKO pMSC expressed CD80 compared with 80% of GTKO pAEC without activation. After pIFN-γ activation, GTKO pAEC upregulated CD86 mRNA level stronger than GTKO pMSC. The human CD4(+) T-cell response to GTKO pMSC was significantly weaker than that to GTKO pAEC, even after pIFN-γ activation. More than 99% of GTKO/CD46 pMSC expressed hCD46. Human peripheral blood mononuclear cells and CD4(+) T-cell responses to GTKO and GTKO/CD46 pMSC were comparable with those to hMSC, and all were significantly lower than to GTKO pAEC. GTKO/CD46 pMSC downregulated human T-cell proliferation as efficiently as hMSC. The level of proinflammatory cytokines IL-2, IFN-γ, TNF-α, and sCD40L correlated with the downregulation of T-cell proliferation by all types of MSC. Genetically modified pMSC is significantly less immunogenic than WT pMSC. GTKO/CD46 pMSC downregulates the human T-cell responses to pig antigens as efficiently as human MSC, which can be advantageous for therapeutic cell xenotransplantation. © 2011 John Wiley & Sons A/S.
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Wang, Jun; Tang, YongYong; Liu, Hao; Zhang, Bin; Chen, Hu
2013-01-01
A protective reagent for ARI should have the ability to repair injured tissue caused by radiation and prevent continuous damage from secondary risk factors. Trx-1 was explored as a candidate therapy for ARI, as it scavenges reactive oxygen species, regulates cell growth and differentiation, participates in immune reactions, and inhibits apoptosis by acting inside and/or outside cells. Trx-1 can also decrease excessive inflammation in ARI by regulating the creation of inflamed media, by inhibiting the activation of complement, and by reducing the chemotaxis, adhesion, and migration of inflammatory cells. As effectively and stably expressing exogenous genes in the long term and regulating immune inflammation and tissue repair, MSC are a good choice for Trx-1 gene therapy. In this study, Trx-1-overexpressing hucMSC-Trx-1 were obtained by adenoviral vector-mediated infection. We first measured the redox capacity of hucMSC-Trx-1 with an antioxidant capacity (T-AOC) assay, a hydrogen peroxide (H2O2) content determination assay in vivo, a H2O2-induced oxidation hemolysis assay, and a lipid peroxidation assay in vitro. Then, we measured survival time, the protection of the hematopoietic system, and the regulation of inflammation in important organs in three treatment groups of NOD/SCID mice (treated with hucMSC-Trx-1, with hucMSC, and with saline) that were exposed to 4.5 Gy 60Co-γ-ray radiation. The hucMSC-Trx-1 group achieved superior antioxidation results, protecting bone marrow hematopoietic stem cells (Lin−CD117+: hucMSC-Trx-1 vs. hucMSC, P<0.05; hucMSC-Trx-1 vs. NS, P<0.01), promoting the formation of red blood cells and hemoglobin (hucMSC-Trx-1 vs. hucMSC or NS, P<0.05), reducing inflammation and damage in important organs (Bone marrow and lung: hucMSC-Trx-1 vs. NS, P<0.01; hucMSC-Trx-1 vs. hucMSC, P<0.05. Liver and intestine: hucMSC-Trx-1 vs. NS, P<0.05; hucMSC-Trx-1 vs. hucMSC, P<0.05), and prolonging survival (hucMSC-Trx-1 vs. hucMSC or NS, P<0.01). Therefore, hucMSC-Trx-1 combines the merits of gene and cell therapy as a multifunctional radioprotector for ARI. PMID:24223778
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Hu, JiangWei; Yang, ZaiLiang; Wang, Jun; Tang, YongYong; Liu, Hao; Zhang, Bin; Chen, Hu
2013-01-01
A protective reagent for ARI should have the ability to repair injured tissue caused by radiation and prevent continuous damage from secondary risk factors. Trx-1 was explored as a candidate therapy for ARI, as it scavenges reactive oxygen species, regulates cell growth and differentiation, participates in immune reactions, and inhibits apoptosis by acting inside and/or outside cells. Trx-1 can also decrease excessive inflammation in ARI by regulating the creation of inflamed media, by inhibiting the activation of complement, and by reducing the chemotaxis, adhesion, and migration of inflammatory cells. As effectively and stably expressing exogenous genes in the long term and regulating immune inflammation and tissue repair, MSC are a good choice for Trx-1 gene therapy. In this study, Trx-1-overexpressing hucMSC-Trx-1 were obtained by adenoviral vector-mediated infection. We first measured the redox capacity of hucMSC-Trx-1 with an antioxidant capacity (T-AOC) assay, a hydrogen peroxide (H2O2) content determination assay in vivo, a H2O2-induced oxidation hemolysis assay, and a lipid peroxidation assay in vitro. Then, we measured survival time, the protection of the hematopoietic system, and the regulation of inflammation in important organs in three treatment groups of NOD/SCID mice (treated with hucMSC-Trx-1, with hucMSC, and with saline) that were exposed to 4.5 Gy (60)Co-γ-ray radiation. The hucMSC-Trx-1 group achieved superior antioxidation results, protecting bone marrow hematopoietic stem cells (Lin(-)CD117(+): hucMSC-Trx-1 vs. hucMSC, P<0.05; hucMSC-Trx-1 vs. NS, P<0.01), promoting the formation of red blood cells and hemoglobin (hucMSC-Trx-1 vs. hucMSC or NS, P<0.05), reducing inflammation and damage in important organs (Bone marrow and lung: hucMSC-Trx-1 vs. NS, P<0.01; hucMSC-Trx-1 vs. hucMSC, P<0.05. Liver and intestine: hucMSC-Trx-1 vs. NS, P<0.05; hucMSC-Trx-1 vs. hucMSC, P<0.05), and prolonging survival (hucMSC-Trx-1 vs. hucMSC or NS, P<0.01). Therefore, hucMSC-Trx-1 combines the merits of gene and cell therapy as a multifunctional radioprotector for ARI.
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de Witte, Samantha F H; Merino, Ana M; Franquesa, Marcella; Strini, Tanja; van Zoggel, Johanna A A; Korevaar, Sander S; Luk, Franka; Gargesha, Madhu; O'Flynn, Lisa; Roy, Debashish; Elliman, Steve J; Newsome, Philip N; Baan, Carla C; Hoogduijn, Martin J
2017-06-08
Mesenchymal stromal cells (MSC) possess immunomodulatory properties and low immunogenicity, both crucial properties for their development into an effective cellular immunotherapy. They have shown benefit in clinical trials targeting liver diseases; however the efficacy of MSC therapy will benefit from improvement of the immunomodulatory and immunogenic properties of MSC. MSC derived from human umbilical cords (ucMSC) were treated for 3 days in vitro with various inflammatory factors, interleukins, vitamins and serum deprivation. Their immunogenicity and immunomodulatory capacity were examined by gene-expression analysis, surface-marker expressions, IDO activity, PGE 2 secretion and inhibition of T cell proliferation and IFNγ production. Furthermore, their activation of NK cell cytotoxicity was investigated via CD107a expression on NK cells. The immunomodulatory capacity, biodistribution and survival of pre-treated ucMSC were investigated in a CCl 4 -induced liver disease mouse model. In addition, capacity of pre-treated MSC to ameliorate liver inflammation was examined in an ex vivo liver inflammation co-culture model. IFN-γ and a multiple cytokine cocktail (MC) consisting of IFN-γ, TGFβ and retinoic acid upregulated the expression of immunomodulatory factor PD-L1 and IDO activity. Subsequently, both treatments enhanced the capacity of ucMSC to inhibit CD4 and CD8 T cell proliferation and IFN-γ production. The susceptibility of ucMSC for NK cell lysis was decreased by IFN-β, TGFβ and MC treatment. In vivo, no immunomodulation was observed by the ucMSC. Four hours after intravenous infusion in mice with CCl 4 -induced inflammatory liver injury, the majority of ucMSC were trapped in the lungs. Rapid clearance of ucMSC(VitB 6 ), ucMSC(Starv + VitB 6 ) and ucMSC(MC) and altered bio-distribution of ucMSC(TGFβ) compared to untreated ucMSC was observed. In the ex vivo co-culture system with inflammatory liver slices ucMSC(MC) showed significantly enhanced modulatory capacity compared to untreated ucMSC. The present study demonstrates the responsiveness of ucMSC to in vitro optimisation treatment. The observed improvements in immunomodulatory capacity as well as immunogenicity after MC treatment may improve the efficacy of ucMSC as immunotherapy targeted towards liver inflammation.
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Multiple scattering corrections to the Beer-Lambert law. 1: Open detector.
Tam, W G; Zardecki, A
1982-07-01
Multiple scattering corrections to the Beer-Lambert law are analyzed by means of a rigorous small-angle solution to the radiative transfer equation. Transmission functions for predicting the received radiant power-a directly measured quantity in contrast to the spectral radiance in the Beer-Lambert law-are derived. Numerical algorithms and results relating to the multiple scattering effects for laser propagation in fog, cloud, and rain are presented.
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Method for measuring multiple scattering corrections between liquid scintillators
DOE Office of Scientific and Technical Information (OSTI.GOV)
Verbeke, J. M.; Glenn, A. M.; Keefer, G. J.
2016-04-11
In this study, a time-of-flight method is proposed to experimentally quantify the fractions of neutrons scattering between scintillators. An array of scintillators is characterized in terms of crosstalk with this method by measuring a californium source, for different neutron energy thresholds. The spectral information recorded by the scintillators can be used to estimate the fractions of neutrons multiple scattering. With the help of a correction to Feynman's point model theory to account for multiple scattering, these fractions can in turn improve the mass reconstruction of fissile materials under investigation.
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Activity of a C-terminal plant homeodomain (PHD) of Msc1 is essential for function.
Qiu, Xinxing; Dul, Barbara E; Walworth, Nancy C
2010-11-19
Msc1, a member of the Jarid1 family of putative histone demethylases, is required for chromosome stability in fission yeast. Msc1 associates with the Swr1 complex that facilitates deposition of histone H2A.Z into chromatin. To assess the function of Msc1 in the Swr1 complex, domains of Msc1 necessary for interaction with Swr1 were identified. The C-terminal plant homeodomain (PHD) 2 and PHD3 of Msc1 are sufficient to confer association with Swr1 and allow Msc1 to function in the context of kinetochore mutants. On the other hand, a mutant with a single amino acid substitution in PHD2 within the full-length Msc1 protein retains the ability to bind to Swr1 but eliminates the function of Msc1 in combination with kinetochore mutants. Thus, Swr1 association is critical but not sufficient for Msc1 function. An activity of Msc1 that depends on the cysteine residue within PHD2 of Msc1 is likewise critical for function. On the basis of our observation that the PHDs of Msc1 act as E3 ubiquitin ligases and that mutations of cysteine residues within those domains abolish ligase activity, we speculate that the ability of Msc1 to facilitate ubiquitin transfer is critical for the function it mediates through its association with Swr1.
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Activity of a C-terminal Plant Homeodomain (PHD) of Msc1 Is Essential for Function*
Qiu, Xinxing; Dul, Barbara E.; Walworth, Nancy C.
2010-01-01
Msc1, a member of the Jarid1 family of putative histone demethylases, is required for chromosome stability in fission yeast. Msc1 associates with the Swr1 complex that facilitates deposition of histone H2A.Z into chromatin. To assess the function of Msc1 in the Swr1 complex, domains of Msc1 necessary for interaction with Swr1 were identified. The C-terminal plant homeodomain (PHD) 2 and PHD3 of Msc1 are sufficient to confer association with Swr1 and allow Msc1 to function in the context of kinetochore mutants. On the other hand, a mutant with a single amino acid substitution in PHD2 within the full-length Msc1 protein retains the ability to bind to Swr1 but eliminates the function of Msc1 in combination with kinetochore mutants. Thus, Swr1 association is critical but not sufficient for Msc1 function. An activity of Msc1 that depends on the cysteine residue within PHD2 of Msc1 is likewise critical for function. On the basis of our observation that the PHDs of Msc1 act as E3 ubiquitin ligases and that mutations of cysteine residues within those domains abolish ligase activity, we speculate that the ability of Msc1 to facilitate ubiquitin transfer is critical for the function it mediates through its association with Swr1. PMID:20858896
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Harman, Rebecca M; Yang, Steven; He, Megan K; Van de Walle, Gerlinde R
2017-07-04
The prevalence of chronic skin wounds in humans is high, and treatment is often complicated by the presence of pathogenic bacteria. Therefore, safe and innovative treatments to reduce the bacterial load in cutaneous wounds are needed. Mesenchymal stromal cells (MSC) are known to provide paracrine signals that act on resident skin cells to promote wound healing, but their potential antibacterial activities are not well described. The present study was designed to examine the antibacterial properties of MSC from horses, as this animal model offers a readily translatable model for MSC therapies in humans. Specifically, we aimed to (i) evaluate the in vitro effects of equine MSC on the growth of representative gram-negative and gram-positive bacterial species commonly found in skin wounds and (ii) define the mechanisms by which MSC inhibit bacterial growth. MSC were isolated from the peripheral blood of healthy horses. Gram-negative E. coli and gram-positive S. aureus were cultured in the presence of MSC and MSC conditioned medium (CM), containing all factors secreted by MSC. Bacterial growth was measured by plating bacteria and counting viable colonies or by reading the absorbance of bacterial cultures. Bacterial membrane damage was detected by incorporation of N-phenyl-1-naphthylamine (NPN). Antimicrobial peptide (AMP) gene and protein expression by equine MSC were determined by RT-PCR and Western blot analysis, respectively. Blocking of AMP activity of MSC CM was achieved using AMP-specific antibodies. We found that equine MSC and MSC CM inhibit the growth of E. coli and S. aureus, and that MSC CM depolarizes the cell membranes of these bacteria. In addition, we found that equine MSC CM contains AMPs, and blocking these AMPs with antibodies reduces the effects of MSC CM on bacteria. Our results demonstrate that equine MSC inhibit bacterial growth and secrete factors that compromise the membrane integrity of bacteria commonly found in skin wounds. We also identified four specific AMPs produced by equine MSC. The secretion of AMPs may contribute to the value of MSC as a therapy for cutaneous wounds in both horses and humans.
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A modified TEW approach to scatter correction for In-111 and Tc-99m dual-isotope small-animal SPECT.
Prior, Paul; Timmins, Rachel; Petryk, Julia; Strydhorst, Jared; Duan, Yin; Wei, Lihui; Glenn Wells, R
2016-10-01
In dual-isotope (Tc-99m/In-111) small-animal single-photon emission computed tomography (SPECT), quantitative accuracy of Tc-99m activity measurements is degraded due to the detection of Compton-scattered photons in the Tc-99m photopeak window, which originate from the In-111 emissions (cross talk) and from the Tc-99m emission (self-scatter). The standard triple-energy window (TEW) estimates the total scatter (self-scatter and cross talk) using one scatter window on either side of the Tc-99m photopeak window, but the estimate is biased due to the presence of unscattered photons in the scatter windows. The authors present a modified TEW method to correct for total scatter that compensates for this bias and evaluate the method in phantoms and in vivo. The number of unscattered Tc-99m and In-111 photons present in each scatter-window projection is estimated based on the number of photons detected in the photopeak of each isotope, using the isotope-dependent energy resolution of the detector. The camera-head-specific energy resolutions for the 140 keV Tc-99m and 171 keV In-111 emissions were determined experimentally by separately sampling the energy spectra of each isotope. Each sampled spectrum was fit with a Linear + Gaussian function. The fitted Gaussian functions were integrated across each energy window to determine the proportion of unscattered photons from each emission detected in the scatter windows. The method was first tested and compared to the standard TEW in phantoms containing Tc-99m:In-111 activity ratios between 0.15 and 6.90. True activities were determined using a dose calibrator, and SPECT activities were estimated from CT-attenuation-corrected images with and without scatter-correction. The method was then tested in vivo in six rats using In-111-liposome and Tc-99m-tetrofosmin to generate cross talk in the area of the myocardium. The myocardium was manually segmented using the SPECT and CT images, and partial-volume correction was performed using a template-based approach. The rat heart was counted in a well-counter to determine the true activity. In the phantoms without correction for Compton-scatter, Tc-99m activity quantification errors as high as 85% were observed. The standard TEW method quantified Tc-99m activity with an average accuracy of -9.0% ± 0.7%, while the modified TEW was accurate within 5% of truth in phantoms with Tc-99m:In-111 activity ratios ≥0.52. Without scatter-correction, In-111 activity was quantified with an average accuracy of 4.1%, and there was no dependence of accuracy on the activity ratio. In rat myocardia, uncorrected images were overestimated by an average of 23% ± 5%, and the standard TEW had an accuracy of -13.8% ± 1.6%, while the modified TEW yielded an accuracy of -4.0% ± 1.6%. Cross talk and self-scatter were shown to produce quantification errors in phantoms as well as in vivo. The standard TEW provided inaccurate results due to the inclusion of unscattered photons in the scatter windows. The modified TEW improved the scatter estimate and reduced the quantification errors in phantoms and in vivo.
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Characterization of Scattered X-Ray Photons in Dental Cone-Beam Computed Tomography.
Yang, Ching-Ching
2016-01-01
Scatter is a very important artifact causing factor in dental cone-beam CT (CBCT), which has a major influence on the detectability of details within images. This work aimed to improve the image quality of dental CBCT through scatter correction. Scatter was estimated in the projection domain from the low frequency component of the difference between the raw CBCT projection and the projection obtained by extrapolating the model fitted to the raw projections acquired with 2 different sizes of axial field-of-view (FOV). The function for curve fitting was optimized by using Monte Carlo simulation. To validate the proposed method, an anthropomorphic phantom and a water-filled cylindrical phantom with rod inserts simulating different tissue materials were scanned using 120 kVp, 5 mA and 9-second scanning time covering an axial FOV of 4 cm and 13 cm. The detectability of the CT image was evaluated by calculating the contrast-to-noise ratio (CNR). Beam hardening and cupping artifacts were observed in CBCT images without scatter correction, especially in those acquired with 13 cm FOV. These artifacts were reduced in CBCT images corrected by the proposed method, demonstrating its efficacy on scatter correction. After scatter correction, the image quality of CBCT was improved in terms of target detectability which was quantified as the CNR for rod inserts in the cylindrical phantom. Hopefully the calculations performed in this work can provide a route to reach a high level of diagnostic image quality for CBCT imaging used in oral and maxillofacial structures whilst ensuring patient dose as low as reasonably achievable, which may ultimately make CBCT scan a reliable and safe tool in clinical practice.
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Effects of Freeze-Thawing and Intravenous Infusion on Mesenchymal Stromal Cell Gene Expression.
Hoogduijn, Martin J; de Witte, Samantha F H; Luk, Franka; van den Hout-van Vroonhoven, Mirjam C G N; Ignatowicz, Lech; Catar, Rusan; Strini, Tanja; Korevaar, Sander S; van IJcken, Wilfred F J; Betjes, Michiel G H; Franquesa, Marcella; Moll, Guido; Baan, Carla C
2016-04-15
Mesenchymal stromal cells (MSC) are increasingly used as an investigative therapeutic product for immune disorders and degenerative disease. Typically, MSC are isolated from human tissue, expanded in culture, and cryopreserved until usage. The safety and efficacy of MSC therapy will depend on the phenotypical and functional characteristics of MSC. The freeze-thawing procedure may change these characteristics. Furthermore, the cells encounter a microenvironment after administration that may impact their properties. It has been demonstrated that the majority of MSC localize to the lungs after intravenous infusion, making this the site to study the effects of the in vivo milieu on administered MSC. In this study, we investigated the effect of freeze-thawing and the mouse lung microenvironment on human adipose tissue-derived MSC. There were effects of freeze-thawing on the whole genome expression profile of MSC, although the effects did not exceed interdonor differences. There were no major changes in the expression of hemostatic regulators on transcriptional level, but significantly increased expression of procoagulant tissue factor on the surface of thawed adipose MSC, correlating with increased procoagulant activity of thawed cells. Exposure for 2 h to the lung microenvironment had a major effect on MSC gene expression and affected several immunological pathways. This indicates that MSC undergo functional changes shortly after infusion and this may influence the efficacy of MSC to modulate inflammatory responses. The results of this study demonstrate that MSC rapidly alter in response to the local milieu and disease-specific conditions may shape MSC after administration.
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Wagner, Wolfgang; Feldmann, Robert E; Seckinger, Anja; Maurer, Martin H; Wein, Frederik; Blake, Jonathon; Krause, Ulf; Kalenka, Armin; Bürgers, Heinrich F; Saffrich, Rainer; Wuchter, Patrick; Kuschinsky, Wolfgang; Ho, Anthony D
2006-04-01
Mesenchymal stem cells (MSC) raise high hopes in clinical applications. However, the lack of common standards and a precise definition of MSC preparations remains a major obstacle in research and application of MSC. Whereas surface antigen markers have failed to precisely define this population, a combination of proteomic data and microarray data provides a new dimension for the definition of MSC preparations. In our continuing effort to characterize MSC, we have analyzed the differential transcriptome and proteome expression profiles of MSC preparations isolated from human bone marrow under two different expansion media (BM-MSC-M1 and BM-MSC-M2). In proteomics, 136 protein spots were unambiguously identified by MALDI-TOF-MS and corresponding cDNA spots were selected on our "Human Transcriptome cDNA Microarray." Combination of datasets revealed a correlation in differential gene expression and protein expression of BM-MSC-M1 vs BM-MSC-M2. Genes involved in metabolism were more highly expressed in BM-MSC-M1, whereas genes involved in development, morphogenesis, extracellular matrix, and differentiation were more highly expressed in BM-MSC-M2. Interchanging culture conditions for 8 days revealed that differential expression was retained in several genes whereas it was altered in others. Our results have provided evidence that homogeneous BM-MSC preparations can reproducibly be isolated under standardized conditions, whereas culture conditions exert a prominent impact on transcriptome, proteome, and cellular organization of BM-MSC.
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Fractional Factorial Design to Investigate Stromal Cell Regulation of Macrophage Plasticity
Barminko, Jeffrey A.; Nativ, Nir I.; Schloss, Rene; Yarmush, Martin L.
2018-01-01
Understanding the regulatory networks which control specific macrophage phenotypes is essential in identifying novel targets to correct macrophage mediated clinical disorders, often accompanied by inflammatory events. Since mesenchymal stromal cells (MSCs) have been shown to play key roles in regulating immune functions predominantly via a large number of secreted products, we used a fractional factorial approach to streamline experimental evaluation of MSC mediated inflammatory macrophage regulation. Our macrophage reprogramming metrics, human bone marrow MSC attenuation of macrophage pro-inflammatory M1 TNFα secretion and simultaneous enhanced expression of the M2 macrophage marker, CD206, were used as analysis endpoints. Objective evaluation of a panel of MSC secreted mediators indicated that PGE2 alone was sufficient in facilitating macrophage reprogramming, while IL4 only provided partial reprogramming. Inhibiting stromal cell PGE2 secretion with Indomethacin, reversed the macrophage reprogramming effect. PGE2 reprogramming was mediated through the EP4 receptor and indirectly through the CREB signaling pathway as GSK3 specific inhibitors induced M1 macrophages to express CD206. This reprogramming pathway functioned independently from the M1 suppression pathway, as neither CREB nor GSK3 inhibition reversed PGE2 TNF-α secretion attenuation. In conclusion, fractional factorial experimental design identified stromal derived PGE2 as the factor most important in facilitating macrophage reprogramming, albeit via two unique pathways. PMID:24891120
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The influence of macrophages on mesenchymal stromal cell therapy: passive or aggressive agents?
Carty, F.; English, K.
2017-01-01
Summary Mesenchymal stromal cells (MSC) have emerged as promising cell therapies for multiple conditions based on demonstrations of their potent immunomodulatory and regenerative capacities in models of inflammatory disease. Understanding the effects of MSC on T cells has dominated the majority of work carried out in this field to date; recently, however, a number of studies have shown that the therapeutic effect of MSC requires the presence of macrophages. It is timely to review the mechanisms and manner by which MSC modulate macrophage populations in order to design more effective MSC therapies and clinical studies. A complex cross‐talk exists through which MSC and macrophages communicate, a communication that is not controlled exclusively by MSC. Here, we examine the evidence that suggests that MSC not only respond to inflammatory macrophages and adjust their secretome accordingly, but also that macrophages respond to encounters with MSC, creating a feedback loop which contributes to the immune regulation observed following MSC therapy. Future studies examining the effects of MSC on macrophages should consider the antagonistic role that macrophages play in this exchange. PMID:28108980
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Conjugate adaptive optics with remote focusing in multiphoton microscopy
NASA Astrophysics Data System (ADS)
Tao, Xiaodong; Lam, Tuwin; Zhu, Bingzhao; Li, Qinggele; Reinig, Marc R.; Kubby, Joel
2018-02-01
The small correction volume for conventional wavefront shaping methods limits their application in biological imaging through scattering media. In this paper, we take advantage of conjugate adaptive optics (CAO) and remote focusing (CAORF) to achieve three-dimensional (3D) scanning through a scattering layer with a single correction. Our results show that the proposed system can provide 10 times wider axial field of view compared with a conventional conjugate AO system when 16,384 segments are used on a spatial light modulator. We demonstrate two-photon imaging with CAORF through mouse skull. The fluorescent microspheres embedded under the scattering layers can be clearly observed after applying the correction.
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Reppel, Loïc; Schiavi, Jessica; Charif, Naceur; Leger, Léonore; Yu, Hao; Pinzano, Astrid; Henrionnet, Christel; Stoltz, Jean-François; Bensoussan, Danièle; Huselstein, Céline
2015-12-30
Due to their intrinsic properties, stem cells are promising tools for new developments in tissue engineering and particularly for cartilage tissue regeneration. Although mesenchymal stromal/stem cells from bone marrow (BM-MSC) have long been the most used stem cell source in cartilage tissue engineering, they have certain limits. Thanks to their properties such as low immunogenicity and particularly chondrogenic differentiation potential, mesenchymal stromal/stem cells from Wharton's jelly (WJ-MSC) promise to be an interesting source of MSC for cartilage tissue engineering. In this study, we propose to evaluate chondrogenic potential of WJ-MSC embedded in alginate/hyaluronic acid hydrogel over 28 days. Hydrogels were constructed by the original spraying method. Our main objective was to evaluate chondrogenic differentiation of WJ-MSC on three-dimensional scaffolds, without adding growth factors, at transcript and protein levels. We compared the results to those obtained from standard BM-MSC. After 3 days of culture, WJ-MSC seemed to be adapted to their new three-dimensional environment without any detectable damage. From day 14 and up to 28 days, the proportion of WJ-MSC CD73(+), CD90(+), CD105(+) and CD166(+) decreased significantly compared to monolayer marker expression. Moreover, WJ-MSC and BM-MSC showed different phenotype profiles. After 28 days of scaffold culture, our results showed strong upregulation of cartilage-specific transcript expression. WJ-MSC exhibited greater type II collagen synthesis than BM-MSC at both transcript and protein levels. Furthermore, our work highlighted a relevant result showing that WJ-MSC expressed Runx2 and type X collagen at lower levels than BM-MSC. Once seeded in the hydrogel scaffold, WJ-MSC and BM-MSC have different profiles of chondrogenic differentiation at both the phenotypic level and matrix synthesis. After 4 weeks, WJ-MSC, embedded in a three-dimensional environment, were able to adapt to their environment and express specific cartilage-related genes and matrix proteins. Today, WJ-MSC represent a real alternative source of stem cells for cartilage tissue engineering.
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Interplay of threshold resummation and hadron mass corrections in deep inelastic processes
Accardi, Alberto; Anderle, Daniele P.; Ringer, Felix
2015-02-01
We discuss hadron mass corrections and threshold resummation for deep-inelastic scattering lN-->l'X and semi-inclusive annihilation e +e - → hX processes, and provide a prescription how to consistently combine these two corrections respecting all kinematic thresholds. We find an interesting interplay between threshold resummation and target mass corrections for deep-inelastic scattering at large values of Bjorken x B. In semi-inclusive annihilation, on the contrary, the two considered corrections are relevant in different kinematic regions and do not affect each other. A detailed analysis is nonetheless of interest in the light of recent high precision data from BaBar and Belle onmore » pion and kaon production, with which we compare our calculations. For both deep inelastic scattering and single inclusive annihilation, the size of the combined corrections compared to the precision of world data is shown to be large. Therefore, we conclude that these theoretical corrections are relevant for global QCD fits in order to extract precise parton distributions at large Bjorken x B, and fragmentation functions over the whole kinematic range.« less
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KIM, JAEHYUP; BREUNIG, MELISSA J.; ESCALANTE, LEAH E.; BHATIA, NEEHAR; DENU, RYAN A.; DOLLAR, BRIDGET A.; STEIN, ANDREW P.; HANSON, SUMMER E.; NADERI, NADIA; RADEK, JAMES; HAUGHY, DERMOT; BLOOM, DEBRA D.; ASSADI-PORTER, FARIBA M.; HEMATTI, PEIMAN
2012-01-01
Background aims Mesenchymal stromal cells (MSC) have now been shown to reside in numerous tissues throughout the body, including the pancreas. Ex vivo culture-expanded MSC derived from many tissues display important interactions with different types of immune cells in vitro and potentially play a significant role in tissue homeostasis in vivo. In this study, we investigated the biologic and immunomodulatory properties of human pancreatic islet-derived MSC. Methods We culture-expanded MSC from cadaveric human pancreatic islets and characterized them using flow cytometry, differentiation assays and nuclear magnetic resonance-based metabolomics. We also investigated the immunologic properties of pancreatic islet-derived MSC compared with bone marrow (BM) MSC. Results Pancreatic islet and BM-derived MSC expressed the same cell-surface markers by flow cytometry, and both could differentiate into bone, fat and cartilage. Metabolomics analysis of MSC from BM and pancreatic islets also showed a similar set of metabolic markers but quantitative polymerase chain reactions showed that pancreatic islet MSC expressed more interleukin(IL)-1b, IL-6, STAT3 and FGF9 compared with BM MSC, and less IL-10. However, similar to BM MSC, pancreatic islet MSC were able to suppress proliferation of allogeneic T lymphocytes stimulated with anti-CD3 and anti-CD28 antibodies. Conclusions Our in vitro analysis shows pancreatic islet-derived MSC have phenotypic, biologic and immunomodulatory characteristics similar, but not identical, to BM-derived MSC. We propose that pancreatic islet-derived MSC could potentially play an important role in improving the outcome of pancreatic islet transplantation by promoting engraftment and creating a favorable immune environment for long-term survival of islet allografts. PMID:22571381
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Qin, Sharon Q; Kusuma, Gina D; Al-Sowayan, Batla; Pace, Rishika A; Isenmann, Sandra; Pertile, Mark D; Gronthos, Stan; Abumaree, Mohamed H; Brennecke, Shaun P; Kalionis, Bill
2016-03-01
Human placental mesenchymal stem/stromal cells (MSC) are an attractive source of MSC with great therapeutic potential. However, primary MSC are difficult to study in vitro due to their limited lifespan and patient-to-patient variation. Fetal and maternal MSC were prepared from cells of the chorionic and basal plates of the placenta, respectively. Fetal and maternal MSC were transduced with the human telomerase reverse transcriptase (hTERT). Conventional stem cell assays assessed the MSC characteristics of the cell lines. Functional assays for cell proliferation, cell migration and ability to form colonies in soft agar were used to assess the whether transduced cells retained properties of primary MSC. Fetal chorionic and maternal MSC were successfully transduced with hTERT to create the cell lines CMSC29 and DMSC23 respectively. The lifespans of CMSC29 and DMSC23 were extended in cell culture. Both cell lines retained important MSC characteristics including cell surface marker expression and multipotent differentiation potential. Neither of the cell lines was tumourigenic in vitro. Gene expression differences were observed between CMSC29 and DMSC23 cells and their corresponding parent, primary MSC. Both cell lines show similar migration potential to their corresponding primary, parent MSC. The data show that transduced MSC retained important functional properties of the primary MSC. There were gene expression and functional differences between cell lines CMSC29 and DMSC23 that reflect their different tissue microenvironments of the parent, primary MSC. CMSC29 and DMSC23 cell lines could be useful tools for optimisation and functional studies of MSC. Copyright © 2016 Elsevier Ltd. All rights reserved.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Fiedler, Tomas, E-mail: tomas.fiedler@med.uni-rostock.de; Salamon, Achim; Adam, Stefanie
Adult mesenchymal stem cells (MSC) are present in several tissues, e.g. bone marrow, heart muscle, brain and subcutaneous adipose tissue. In invasive infections MSC get in contact with bacteria and bacterial components. Not much is known about how bacterial pathogens interact with MSC and how contact to bacteria influences MSC viability and differentiation potential. In this study we investigated the impact of three different wound infection relevant bacteria, Escherichia coli, Staphylococcus aureus, and Streptococcus pyogenes, and the cell wall components lipopolysaccharide (LPS; Gram-negative bacteria) and lipoteichoic acid (LTA; Gram-positive bacteria) on viability, proliferation, and osteogenic as well as adipogenic differentiationmore » of human adipose tissue-derived mesenchymal stem cells (adMSC). We show that all three tested species were able to attach to and internalize into adMSC. The heat-inactivated Gram-negative E. coli as well as LPS were able to induce proliferation and osteogenic differentiation but reduce adipogenic differentiation of adMSC. Conspicuously, the heat-inactivated Gram-positive species showed the same effects on proliferation and adipogenic differentiation, while its cell wall component LTA exhibited no significant impact on adMSC. Therefore, our data demonstrate that osteogenic and adipogenic differentiation of adMSC is influenced in an oppositional fashion by bacterial antigens and that MSC-governed regeneration is not necessarily reduced under infectious conditions. - Highlights: • Staphylococcus aureus, Streptococcus pyogenes and Escherichia coli bind to and internalize into adMSC. • Heat-inactivated cells of these bacterial species trigger proliferation of adMSC. • Heat-inactivated E. coli and LPS induce osteogenic differentiation of adMSC. • Heat-inactivated E. coli and LPS reduce adipogenic differentiation of adMSC. • LTA does not influence adipogenic or osteogenic differentiation of adMSC.« less
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Klinker, Matthew W.; Marklein, Ross A.; Lo Surdo, Jessica L.; Wei, Cheng-Hong
2017-01-01
Human mesenchymal stromal cell (MSC) lines can vary significantly in their functional characteristics, and the effectiveness of MSC-based therapeutics may be realized by finding predictive features associated with MSC function. To identify features associated with immunosuppressive capacity in MSCs, we developed a robust in vitro assay that uses principal-component analysis to integrate multidimensional flow cytometry data into a single measurement of MSC-mediated inhibition of T-cell activation. We used this assay to correlate single-cell morphological data with overall immunosuppressive capacity in a cohort of MSC lines derived from different donors and manufacturing conditions. MSC morphology after IFN-γ stimulation significantly correlated with immunosuppressive capacity and accurately predicted the immunosuppressive capacity of MSC lines in a validation cohort. IFN-γ enhanced the immunosuppressive capacity of all MSC lines, and morphology predicted the magnitude of IFN-γ–enhanced immunosuppressive activity. Together, these data identify MSC morphology as a predictive feature of MSC immunosuppressive function. PMID:28283659
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Francois, Sabine; Mouiseddine, Moubarak; Allenet-Lepage, Bénédicte; Voswinkel, Jan; Douay, Luc; Benderitter, Marc; Chapel, Alain
2013-01-01
To evaluate the potential therapeutic effect of the infusion of hMSCs for the correction of liver injuries, we performed total body radiation exposure of NOD/SCID mice. After irradiation, mir-27b level decreases in liver, increasing the directional migration of hMSCs by upregulating SDF1α. A significant increase in plasmatic transaminases levels, apoptosis process in the liver vascular system, and in oxidative stress were observed. hMSC injection induced a decrease in transaminases levels and oxidative stress, a disappearance of apoptotic cells, and an increase in Nrf2, SOD gene expression, which might reduce ROS production in the injured liver. Engrafted hMSCs expressed cytokeratin CK18 and CK19 and AFP genes indicating possible hepatocyte differentiation. The presence of hMSCs expressing VEGF and Ang-1 in the perivascular region, associated with an increased expression of VEGFr1, r2 in the liver, can confer a role of secreting cells to hMSCs in order to maintain the endothelial function. To explain the benefits to the liver of hMSC engraftment, we find that hMSCs secreted NGF, HGF, and anti-inflammatory molecules IL-10, IL1-RA contributing to prevention of apoptosis, increasing cell proliferation in the liver which might correct liver dysfunction. MSCs are potent candidates to repair and protect healthy tissues against radiation damages. PMID:24369528
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Evaluation of a scattering correction method for high energy tomography
NASA Astrophysics Data System (ADS)
Tisseur, David; Bhatia, Navnina; Estre, Nicolas; Berge, Léonie; Eck, Daniel; Payan, Emmanuel
2018-01-01
One of the main drawbacks of Cone Beam Computed Tomography (CBCT) is the contribution of the scattered photons due to the object and the detector. Scattered photons are deflected from their original path after their interaction with the object. This additional contribution of the scattered photons results in increased measured intensities, since the scattered intensity simply adds to the transmitted intensity. This effect is seen as an overestimation in the measured intensity thus corresponding to an underestimation of absorption. This results in artifacts like cupping, shading, streaks etc. on the reconstructed images. Moreover, the scattered radiation provides a bias for the quantitative tomography reconstruction (for example atomic number and volumic mass measurement with dual-energy technique). The effect can be significant and difficult in the range of MeV energy using large objects due to higher Scatter to Primary Ratio (SPR). Additionally, the incident high energy photons which are scattered by the Compton effect are more forward directed and hence more likely to reach the detector. Moreover, for MeV energy range, the contribution of the photons produced by pair production and Bremsstrahlung process also becomes important. We propose an evaluation of a scattering correction technique based on the method named Scatter Kernel Superposition (SKS). The algorithm uses a continuously thickness-adapted kernels method. The analytical parameterizations of the scatter kernels are derived in terms of material thickness, to form continuously thickness-adapted kernel maps in order to correct the projections. This approach has proved to be efficient in producing better sampling of the kernels with respect to the object thickness. This technique offers applicability over a wide range of imaging conditions and gives users an additional advantage. Moreover, since no extra hardware is required by this approach, it forms a major advantage especially in those cases where experimental complexities must be avoided. This approach has been previously tested successfully in the energy range of 100 keV - 6 MeV. In this paper, the kernels are simulated using MCNP in order to take into account both photons and electronic processes in scattering radiation contribution. We present scatter correction results on a large object scanned with a 9 MeV linear accelerator.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Ghrayeb, S. Z.; Ouisloumen, M.; Ougouag, A. M.
2012-07-01
A multi-group formulation for the exact neutron elastic scattering kernel is developed. This formulation is intended for implementation into a lattice physics code. The correct accounting for the crystal lattice effects influences the estimated values for the probability of neutron absorption and scattering, which in turn affect the estimation of core reactivity and burnup characteristics. A computer program has been written to test the formulation for various nuclides. Results of the multi-group code have been verified against the correct analytic scattering kernel. In both cases neutrons were started at various energies and temperatures and the corresponding scattering kernels were tallied.more » (authors)« less
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No evidence for circulating mesenchymal stem cells in patients with organ injury.
Hoogduijn, Martin J; Verstegen, Monique M A; Engela, Anja U; Korevaar, Sander S; Roemeling-van Rhijn, Marieke; Merino, Ana; Franquesa, Marcella; de Jonge, Jeroen; Ijzermans, Jan N; Weimar, Willem; Betjes, Michiel G H; Baan, Carla C; van der Laan, Luc J W
2014-10-01
Mesenchymal stem cells (MSC) are present in the bone marrow, from where they are thought to migrate through the blood stream to the sites of injury. However, virtually all tissues contain resident MSC that may contribute to local regenerative and immunomodulatory processes, thereby hypothetically preempting the need for recruiting MSC through the bloodstream. Although there is some indication for circulating MSC in animal models, there is little solid evidence for the mobilization and migration of MSC in the human circulation. In the present study, we were unable to detect MSC in the blood of healthy individuals. We then searched for MSC in the blood of ten patients with end-stage renal disease, ten patients with end-stage liver disease, and in eight heart transplant patients with biopsy-proven rejection by culturing of mononuclear cells under MSC-supporting culture conditions. In none of these patient categories, MSC were identified in the blood. MSC were, however, found in the blood of a severe trauma patient with multiple fractures, suggesting that disruption of bone marrow leads to the release of MSC into the blood stream. The conclusion of this study is that MSC are not recruited into the circulation in patients with injured solid organs and during aggressive immune responses after transplantation.
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NASA Astrophysics Data System (ADS)
Liu, Yuanyuan; Peng, Yankun; Zhang, Leilei; Dhakal, Sagar; Wang, Caiping
2014-05-01
Pork is one of the highly consumed meat item in the world. With growing improvement of living standard, concerned stakeholders including consumers and regulatory body pay more attention to comprehensive quality of fresh pork. Different analytical-laboratory based technologies exist to determine quality attributes of pork. However, none of the technologies are able to meet industrial desire of rapid and non-destructive technological development. Current study used optical instrument as a rapid and non-destructive tool to classify 24 h-aged pork longissimus dorsi samples into three kinds of meat (PSE, Normal and DFD), on the basis of color L* and pH24. Total of 66 samples were used in the experiment. Optical system based on Vis/NIR spectral acquisition system (300-1100 nm) was self- developed in laboratory to acquire spectral signal of pork samples. Median smoothing filter (M-filter) and multiplication scatter correction (MSC) was used to remove spectral noise and signal drift. Support vector machine (SVM) prediction model was developed to classify the samples based on their comprehensive qualities. The results showed that the classification model is highly correlated with the actual quality parameters with classification accuracy more than 85%. The system developed in this study being simple and easy to use, results being promising, the system can be used in meat processing industry for real time, non-destructive and rapid detection of pork qualities in future.
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Fully relativistic form factor for Thomson scattering.
Palastro, J P; Ross, J S; Pollock, B; Divol, L; Froula, D H; Glenzer, S H
2010-03-01
We derive a fully relativistic form factor for Thomson scattering in unmagnetized plasmas valid to all orders in the normalized electron velocity, beta[over ]=v[over ]/c. The form factor is compared to a previously derived expression where the lowest order electron velocity, beta[over], corrections are included [J. Sheffield, (Academic Press, New York, 1975)]. The beta[over ] expansion approach is sufficient for electrostatic waves with small phase velocities such as ion-acoustic waves, but for electron-plasma waves the phase velocities can be near luminal. At high phase velocities, the electron motion acquires relativistic corrections including effective electron mass, relative motion of the electrons and electromagnetic wave, and polarization rotation. These relativistic corrections alter the scattered emission of thermal plasma waves, which manifest as changes in both the peak power and width of the observed Thomson-scattered spectra.
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Diaphragm correction factors for the FAC-IR-300 free-air ionization chamber.
Mohammadi, Seyed Mostafa; Tavakoli-Anbaran, Hossein
2018-02-01
A free-air ionization chamber FAC-IR-300, designed by the Atomic Energy Organization of Iran, is used as the primary Iranian national standard for the photon air kerma. For accurate air kerma measurements, the contribution from the scattered photons to the total energy released in the collecting volume must be eliminated. One of the sources of scattered photons is the chamber's diaphragm. In this paper, the diaphragm scattering correction factor, k dia , and the diaphragm transmission correction factor, k tr , were introduced. These factors represent corrections to the measured charge (or current) for the photons scattered from the diaphragm surface and the photons penetrated through the diaphragm volume, respectively. The k dia and k tr values were estimated by Monte Carlo simulations. The simulations were performed for the mono-energetic photons in the energy range of 20 - 300keV. According to the simulation results, in this energy range, the k dia values vary between 0.9997 and 0.9948, and k tr values decrease from 1.0000 to 0.9965. The corrections grow in significance with increasing energy of the primary photons. Copyright © 2017 Elsevier Ltd. All rights reserved.
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Radiative corrections to elastic proton-electron scattering measured in coincidence
NASA Astrophysics Data System (ADS)
Gakh, G. I.; Konchatnij, M. I.; Merenkov, N. P.; Tomasi-Gustafsson, E.
2017-05-01
The differential cross section for elastic scattering of protons on electrons at rest is calculated, taking into account the QED radiative corrections to the leptonic part of interaction. These model-independent radiative corrections arise due to emission of the virtual and real soft and hard photons as well as to vacuum polarization. We analyze an experimental setup when both the final particles are recorded in coincidence and their energies are determined within some uncertainties. The kinematics, the cross section, and the radiative corrections are calculated and numerical results are presented.
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[Mesenchymal stem cells: weapons or dangers for cancer treatment?].
Lazennec, Gwendal
2011-03-01
Mesenchymal stem cells (MSC) have attracted recent attention for their cell therapy potential, based in particular on their immunosuppressive properties, which have served as the basis for the treatment of autoimmune diseases. Interestingly, MSC have been used in cell therapy strategies to deliver therapeutical genes. Cell therapy approaches taking advantages of MSC have been proposed, as MSC display a potential tropsim for tumors. However, all these strategies raise a series of questions about the safety of MSC, as MSC could enhance tumor growth and metastasis. This review summarizes recent findngs about MSC in carcinogenesis. © 2011 médecine/sciences - Inserm / SRMS.
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Receptor control in mesenchymal stem cell engineering
NASA Astrophysics Data System (ADS)
Dalby, Matthew J.; García, Andrés J.; Salmeron-Sanchez, Manuel
2018-03-01
Materials science offers a powerful tool to control mesenchymal stem cell (MSC) growth and differentiation into functional phenotypes. A complex interplay between the extracellular matrix and growth factors guides MSC phenotypes in vivo. In this Review, we discuss materials-based bioengineering approaches to direct MSC fate in vitro and in vivo, mimicking cell-matrix-growth factor crosstalk. We first scrutinize MSC-matrix interactions and how the properties of a material can be tailored to support MSC growth and differentiation in vitro, with an emphasis on MSC self-renewal mechanisms. We then highlight important growth factor signalling pathways and investigate various materials-based strategies for growth factor presentation and delivery. Integrin-growth factor crosstalk in the context of MSC engineering is introduced, and bioinspired material designs with the potential to control the MSC niche phenotype are considered. Finally, we summarize important milestones on the road to MSC engineering for regenerative medicine.
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Mróz, Tomasz L.; Eves-van den Akker, Sebastian; Bernat, Agata; Skarzyńska, Agnieszka; Pryszcz, Leszek; Olberg, Madeline; Havey, Michael J.; Bartoszewski, Grzegorz
2018-01-01
Cucumber (Cucumis sativus L.) has a large, paternally transmitted mitochondrial genome. Cucumber plants regenerated from cell cultures occasionally show paternally transmitted mosaic (MSC) phenotypes, characterized by slower growth, chlorotic patterns on the leaves and fruit, lower fertility, and rearrangements in their mitochondrial DNAs (mtDNAs). MSC lines 3, 12, and 16 originated from different cell cultures all established using the highly inbred, wild-type line B. These MSC lines possess different rearrangements and under-represented regions in their mtDNAs. We completed RNA-seq on normalized and non-normalized cDNA libraries from MSC3, MSC12, and MSC16 to study their nuclear gene-expression profiles relative to inbred B. Results from both libraries indicated that gene expression in MSC12 and MSC16 were more similar to each other than MSC3. Forty-one differentially expressed genes (DEGs) were upregulated and one downregulated in the MSC lines relative to B. Gene functional classifications revealed that more than half of these DEGs are associated with stress-response pathways. Consistent with this observation, we detected elevated levels of hydrogen peroxide throughout leaf tissue in all MSC lines compared to wild-type line B. These results demonstrate that independently produced MSC lines with different mitochondrial polymorphisms show unique and shared nuclear responses. This study revealed genes associated with stress response that could become selection targets to develop cucumber cultivars with increased stress tolerance, and further support of cucumber as a model plant to study nuclear-mitochondrial interactions. PMID:29330162
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Sánchez-Abarca, Luis Ignacio; Rosón-Burgo, Beatriz; Redondo, Alba; Rico, Ana; Preciado, Silvia; Ortega, Rebeca; Rodríguez, Concepción; Muntión, Sandra; Hernández-Hernández, Ángel; De Las Rivas, Javier; González, Marcos; González Porras, José Ramón; del Cañizo, Consuelo; Sánchez-Guijo, Fermín
2017-01-01
There is evidence of continuous bidirectional cross-talk between malignant cells and bone marrow-derived mesenchymal stromal cells (BM-MSC), which favors the emergence and progression of myeloproliferative neoplastic (MPN) diseases. In the current work we have compared the function and gene expression profile of BM-MSC from healthy donors (HD-MSC) and patients with MPN (JAK2V617F), showing no differences in the morphology, proliferation and differentiation capacity between both groups. However, BM-MSC from MPN expressed higher mean fluorescence intensity (MIF) of CD73, CD44 and CD90, whereas CD105 was lower when compared to controls. Gene expression profile of BM-MSC showed a total of 169 genes that were differentially expressed in BM-MSC from MPN patients compared to HD-MSC. In addition, we studied the ability of BM-MSC to support the growth and survival of hematopoietic stem/progenitor cells (HSPC), showing a significant increase in the number of CFU-GM colonies when MPN-HSPC were co-cultured with MPN-MSC. Furthermore, MPN-MSC showed alteration in the expression of genes associated to the maintenance of hematopoiesis, with an overexpression of SPP1 and NF-kB, and a downregulation of ANGPT1 and THPO. Our results suggest that BM-MSC from JAK2+ patients differ from their normal counterparts and favor the maintenance of malignant clonal hematopoietic cells. PMID:28796790
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Bae, Sang-Woo; Lee, Kang-Woog; Park, Jae-Hyun; Lee, JunHee; Jung, Cho-Rok; Yu, JunJie; Kim, Hwi-Yool; Kim, Dae-Hyun
2018-05-31
Tracheal resection has limited applicability. Although various tracheal replacement strategies were performed using artificial prosthesis, synthetic stents and tissue transplantation, the best method in tracheal reconstruction remains to be identified. Recent advances in tissue engineering enabled 3D bioprinting using various biocompatible materials including living cells, thereby making the product clinically applicable. Moreover, clinical interest in mesenchymal stem cell has dramatically increased. Here, rabbit bone marrow-derived mesenchymal stem cells (bMSC) and rabbit respiratory epithelial cells were cultured. The chondrogenic differentiation level of bMSC cultured in regular media (MSC) and that in chondrogenic media (d-MSC) were compared. Dual cell-containing artificial trachea were manufactured using a 3D bioprinting method with epithelial cells and undifferentiated bMSC (MSC group, n = 6) or with epithelial cells and chondrogenic-differentiated bMSC (d-MSC group, n = 6). d-MSC showed a relatively higher level of glycosaminoglycan (GAG) accumulation and chondrogenic marker gene expression than MSC in vitro. Neo-epithelialization and neo-vascularization were observed in all groups in vivo but neo-cartilage formation was only noted in d-MSC. The epithelial cells in the 3D bioprinted artificial trachea were effective in respiratory epithelium regeneration. Chondrogenic-differentiated bMSC had more neo-cartilage formation potential in a short period. Nevertheless, the cartilage formation was observed only in a localized area.
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Experimental testing of four correction algorithms for the forward scattering spectrometer probe
NASA Technical Reports Server (NTRS)
Hovenac, Edward A.; Oldenburg, John R.; Lock, James A.
1992-01-01
Three number density correction algorithms and one size distribution correction algorithm for the Forward Scattering Spectrometer Probe (FSSP) were compared with data taken by the Phase Doppler Particle Analyzer (PDPA) and an optical number density measuring instrument (NDMI). Of the three number density correction algorithms, the one that compared best to the PDPA and NDMI data was the algorithm developed by Baumgardner, Strapp, and Dye (1985). The algorithm that corrects sizing errors in the FSSP that was developed by Lock and Hovenac (1989) was shown to be within 25 percent of the Phase Doppler measurements at number densities as high as 3000/cc.
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SU-E-I-07: An Improved Technique for Scatter Correction in PET
DOE Office of Scientific and Technical Information (OSTI.GOV)
Lin, S; Wang, Y; Lue, K
2014-06-01
Purpose: In positron emission tomography (PET), the single scatter simulation (SSS) algorithm is widely used for scatter estimation in clinical scans. However, bias usually occurs at the essential steps of scaling the computed SSS distribution to real scatter amounts by employing the scatter-only projection tail. The bias can be amplified when the scatter-only projection tail is too small, resulting in incorrect scatter correction. To this end, we propose a novel scatter calibration technique to accurately estimate the amount of scatter using pre-determined scatter fraction (SF) function instead of the employment of scatter-only tail information. Methods: As the SF depends onmore » the radioactivity distribution and the attenuating material of the patient, an accurate theoretical relation cannot be devised. Instead, we constructed an empirical transformation function between SFs and average attenuation coefficients based on a serious of phantom studies with different sizes and materials. From the average attenuation coefficient, the predicted SFs were calculated using empirical transformation function. Hence, real scatter amount can be obtained by scaling the SSS distribution with the predicted SFs. The simulation was conducted using the SimSET. The Siemens Biograph™ 6 PET scanner was modeled in this study. The Software for Tomographic Image Reconstruction (STIR) was employed to estimate the scatter and reconstruct images. The EEC phantom was adopted to evaluate the performance of our proposed technique. Results: The scatter-corrected image of our method demonstrated improved image contrast over that of SSS. For our technique and SSS of the reconstructed images, the normalized standard deviation were 0.053 and 0.182, respectively; the root mean squared errors were 11.852 and 13.767, respectively. Conclusion: We have proposed an alternative method to calibrate SSS (C-SSS) to the absolute scatter amounts using SF. This method can avoid the bias caused by the insufficient tail information and therefore improve the accuracy of scatter estimation.« less
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Human adipose mesenchymal stem cells as potent anti-fibrosis therapy for systemic sclerosis.
Maria, Alexandre T J; Toupet, Karine; Maumus, Marie; Fonteneau, Guillaume; Le Quellec, Alain; Jorgensen, Christian; Guilpain, Philippe; Noël, Danièle
2016-06-01
Displaying immunosuppressive and trophic properties, mesenchymal stem/stromal cells (MSC) are being evaluated as promising therapeutic options in a variety of autoimmune and degenerative diseases. Although benefits may be expected in systemic sclerosis (SSc), a rare autoimmune disease with fibrosis-related mortality, MSC have yet to be evaluated in this specific condition. While autologous approaches could be inappropriate because of functional alterations in MSC from patients, the objective of the present study was to evaluate allogeneic and xenogeneic MSC in the HOCl-induced model of diffuse SSc. We also questioned the source of human MSC and compared bone marrow- (hBM-MSC) and adipose-derived MSC (hASC). HOCl-challenged BALB/c mice received intravenous injection of BM-MSC from syngeneic BALB/c or allogeneic C57BL/6 mice, and xenogeneic hBM-MSC or hASC (3 donors each). Skin thickness was measured during the experiment. At euthanasia, histology, immunostaining, collagen determination and RT-qPCR were performed in skin and lungs. Xenogeneic hBM-MSC were as effective as allogeneic or syngeneic BM-MSC in decreasing skin thickness, expression of Col1, Col3, α-Sma transcripts, and collagen content in skin and lungs. This anti-fibrotic effect was not associated with MSC migration to injured skin or with long-term MSC survival. Interestingly, compared with hBM-MSC, hASC were significantly more efficient in reducing skin fibrosis, which was related to a stronger reduction of TNFα, IL1β, and enhanced ratio of Mmp1/Timp1 in skin and lung tissues. Using primary cells isolated from 3 murine and 6 human individuals, this preclinical study demonstrated similar therapeutic effects using allogeneic or xenogeneic BM-MSC while ASC exerted potent anti-inflammatory and remodeling properties. This sets the proof-of-concept prompting to evaluate the therapeutic efficacy of allogeneic ASC in SSc patients. Copyright © 2016 Elsevier Ltd. All rights reserved.
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[Development of a Striatal and Skull Phantom for Quantitative 123I-FP-CIT SPECT].
Ishiguro, Masanobu; Uno, Masaki; Miyazaki, Takuma; Kataoka, Yumi; Toyama, Hiroshi; Ichihara, Takashi
123 Iodine-labelled N-(3-fluoropropyl) -2β-carbomethoxy-3β-(4-iodophenyl) nortropane ( 123 I-FP-CIT) single photon emission computerized tomography (SPECT) images are used for differential diagnosis such as Parkinson's disease (PD). Specific binding ratio (SBR) is affected by scattering and attenuation in SPECT imaging, because gender and age lead to changes in skull density. It is necessary to clarify and correct the influence of the phantom simulating the the skull. The purpose of this study was to develop phantoms that can evaluate scattering and attenuation correction. Skull phantoms were prepared based on the measuring the results of the average computed tomography (CT) value, average skull thickness of 12 males and 16 females. 123 I-FP-CIT SPECT imaging of striatal phantom was performed with these skull phantoms, which reproduced normal and PD. SPECT images, were reconstructed with scattering and attenuation correction. SBR with partial volume effect corrected (SBR act ) and conventional SBR (SBR Bolt ) were measured and compared. The striatum and the skull phantoms along with 123 I-FP-CIT were able to reproduce the normal accumulation and disease state of PD and further those reproduced the influence of skull density on SPECT imaging. The error rate with the true SBR, SBR act was much smaller than SBR Bolt . The effect on SBR could be corrected by scattering and attenuation correction even if the skull density changes with 123 I-FP-CIT on SPECT imaging. The combination of triple energy window method and CT-attenuation correction method would be the best correction method for SBR act .
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Reis, Monica; McDonald, David; Nicholson, Lindsay; Godthardt, Kathrin; Knobel, Sebastian; Dickinson, Anne M; Filby, Andrew; Wang, Xiao-Nong
2018-03-02
Mesenchymal stromal cells (MSCs) are a promising cell source to develop cell therapy for many diseases. Human platelet lysate (PLT) is increasingly used as an alternative to foetal calf serum (FCS) for clinical-scale MSC production. To date, the global surface protein expression of PLT-expended MSCs (MSC-PLT) is not known. To investigate this, paired MSC-PLT and MSC-FCS were analysed in parallel using high-throughput flow cytometry for the expression of 356 cell surface proteins. MSC-PLT showed differential surface protein expression compared to their MSC-FCS counterpart. Higher percentage of positive cells was observed in MSC-PLT for 48 surface proteins, of which 13 were significantly enriched on MSC-PLT. This finding was validated using multiparameter flow cytometry and further confirmed by quantitative staining intensity analysis. The enriched surface proteins are relevant to increased proliferation and migration capacity, as well as enhanced chondrogenic and osteogenic differentiation properties. In silico network analysis revealed that these enriched surface proteins are involved in three distinct networks that are associated with inflammatory responses, carbohydrate metabolism and cellular motility. This is the first study reporting differential cell surface protein expression between MSC-PLT and MSC-FSC. Further studies are required to uncover the impact of those enriched proteins on biological functions of MSC-PLT.
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NASA Astrophysics Data System (ADS)
Qattan, I. A.
2017-06-01
I present a prediction of the e± elastic scattering cross-section ratio, Re+e-, as determined using a new parametrization of the two-photon exchange (TPE) corrections to electron-proton elastic scattering cross section σR. The extracted ratio is compared to several previous phenomenological extractions, TPE hadronic calculations, and direct measurements from the comparison of electron and positron scattering. The TPE corrections and the ratio Re+e- show a clear change of sign at low Q2, which is necessary to explain the high-Q2 form factors discrepancy while being consistent with the known Q2→0 limit. While my predictions are in generally good agreement with previous extractions, TPE hadronic calculations, and existing world data including the recent two measurements from the CLAS and VEPP-3 Novosibirsk experiments, they are larger than the new OLYMPUS measurements at larger Q2 values.
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Interference detection and correction applied to incoherent-scatter radar power spectrum measurement
NASA Technical Reports Server (NTRS)
Ying, W. P.; Mathews, J. D.; Rastogi, P. K.
1986-01-01
A median filter based interference detection and correction technique is evaluated and the method applied to the Arecibo incoherent scatter radar D-region ionospheric power spectrum is discussed. The method can be extended to other kinds of data when the statistics involved in the process are still valid.
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Marquass, Bastian; Schulz, Ronny; Hepp, Pierre; Zscharnack, Matthias; Aigner, Thomas; Schmidt, Stefanie; Stein, Frank; Richter, Robert; Osterhoff, Georg; Aust, Gabriele; Josten, Christoph; Bader, Augustinus
2011-07-01
The use of predifferentiated mesenchymal stem cells (MSC) leads to better histological results compared with undifferentiated MSC in sheep. This raises the need for a longer term follow-up study and comparison with a clinically established method. We hypothesized that chondrogenic in vitro predifferentiation of autologous MSC embedded in a collagen I hydrogel leads to better structural repair of a chronic osteochondral defect in an ovine stifle joint after 1 year. We further hypothesized that resulting histological results would be comparable with those of chondrocyte-seeded matrix-associated autologous chondrocyte transplantation (MACT). Controlled laboratory study. Predifferentiation period of ovine MSC within collagen gel in vitro was defined by assessment of several cellular and molecular biological parameters. For the animal study, 2 osteochondral lesions (7-mm diameter) were created at the medial femoral condyles of the hind legs in 9 sheep. Implantation of MSC gels was performed 6 weeks after defect creation. Thirty-six defects were divided into 4 treatment groups: (1) chondrogenically predifferentiated MSC gels (pre-MSC gels), (2) undifferentiated MSC gels (un-MSC gels), (3) MACT gels, and (4) untreated controls (UC). Histological, immunohistochemical, and radiological evaluations followed after 12 months. After 12 months in vivo, pre-MSC gels showed significantly better histological outcome compared with un-MSC gels and UC. Compared with MACT gels, the overall scores were higher for O'Driscoll and International Cartilage Repair Society (ICRS). The repair tissue of the pre-MSC group showed immunohistochemical detection of interzonal collagen type II staining. Radiological evaluation supported superior bonding of pre-MSC gels to perilesional native cartilage. Compared with previous work by our group, no degradation of the repair tissue between 6 and 12 months in vivo, particularly in pre-MSC gels, was observed. Repair of chronic osteochondral defects with collagen hydrogels composed of chondrogenically predifferentiated MSC shows no signs of degradation after 1 year in vivo. In addition, pre-MSC gels lead to partially superior histological results compared with articular chondrocytes. The results suggest an encouraging method for future treatment of focal osteochondral defects without donor site morbidity by harvesting articular chondrocytes.
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Local blur analysis and phase error correction method for fringe projection profilometry systems.
Rao, Li; Da, Feipeng
2018-05-20
We introduce a flexible error correction method for fringe projection profilometry (FPP) systems in the presence of local blur phenomenon. Local blur caused by global light transport such as camera defocus, projector defocus, and subsurface scattering will cause significant systematic errors in FPP systems. Previous methods, which adopt high-frequency patterns to separate the direct and global components, fail when the global light phenomenon occurs locally. In this paper, the influence of local blur on phase quality is thoroughly analyzed, and a concise error correction method is proposed to compensate the phase errors. For defocus phenomenon, this method can be directly applied. With the aid of spatially varying point spread functions and local frontal plane assumption, experiments show that the proposed method can effectively alleviate the system errors and improve the final reconstruction accuracy in various scenes. For a subsurface scattering scenario, if the translucent object is dominated by multiple scattering, the proposed method can also be applied to correct systematic errors once the bidirectional scattering-surface reflectance distribution function of the object material is measured.
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Pathogen-free, plasma-poor platelet lysate and expansion of human mesenchymal stem cells.
Iudicone, Paola; Fioravanti, Daniela; Bonanno, Giuseppina; Miceli, Michelina; Lavorino, Claudio; Totta, Pierangela; Frati, Luigi; Nuti, Marianna; Pierelli, Luca
2014-01-27
Supplements to support clinical-grade cultures of mesenchymal stem cells (MSC) are required to promote growth and expansion of these cells. Platelet lysate (PL) is a human blood component which may replace animal serum in MSC cultures being rich in various growth factors. Here, we describe a plasma poor pathogen-free platelet lysate obtained by pooling 12 platelet (PLT) units, to produce a standardized and safe supplement for clinical-grade expansion of MSC. PL lots were obtained by combining 2 6-unit PLT pools in additive solution (AS) following a transfusional-based procedure including pathogen inactivation (PI) by Intercept technology and 3 cycles of freezing/thawing, followed by membrane removal. Three PI-PL and 3 control PL lots were produced to compare their ability to sustain bone marrow derived MSC selection and expansion. Moreover, two further PL, subjected to PI or not, were also produced starting from the same initial PLT pools to evaluate the impact of PI on growth factor concentration and capacity to sustain cell growth. Additional PI-PL lots were used for comparison with fetal bovine serum (FBS) on MSC expansion. Immunoregulatory properties of PI-PL-generated MSC were documented in vitro by mixed lymphocyte culture (MLC) and peripheral blood mononuclear cells (PBMC) mitogen induced proliferation. PI-PL and PL control lots had similar concentrations of 4 well-described growth factors endowed with MSC stimulating ability. Initial growth and MSC expansion by PI-PL and PL controls were comparable either using different MSC populations or in head to head experiments. Moreover, PI-PL and PL control sustained similar MSC growth of frozen/thawed MSC. Multilineage differentiation of PI-derived and PI-PL-derived MSC were maintained in any MSC cultures as well as their immunoregulatory properties. Finally, no direct impact of PI on growth factor concentration and MSC growth support was observed, whereas the capacity of FBS to sustain MSC expansion in basic medium was irrelevant as compared to PL and PI-PL. The replacement of animal additives with human supplements is a basic issue in MSC ex vivo production. PI-PL represents a standardized, plasma-poor, human preparation which appears as a safe and good candidate to stimulate MSC growth in clinical-scale cultures.
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Pathogen-free, plasma-poor platelet lysate and expansion of human mesenchymal stem cells
2014-01-01
Background Supplements to support clinical-grade cultures of mesenchymal stem cells (MSC) are required to promote growth and expansion of these cells. Platelet lysate (PL) is a human blood component which may replace animal serum in MSC cultures being rich in various growth factors. Here, we describe a plasma poor pathogen-free platelet lysate obtained by pooling 12 platelet (PLT) units, to produce a standardized and safe supplement for clinical-grade expansion of MSC. Methods PL lots were obtained by combining 2 6-unit PLT pools in additive solution (AS) following a transfusional-based procedure including pathogen inactivation (PI) by Intercept technology and 3 cycles of freezing/thawing, followed by membrane removal. Three PI-PL and 3 control PL lots were produced to compare their ability to sustain bone marrow derived MSC selection and expansion. Moreover, two further PL, subjected to PI or not, were also produced starting from the same initial PLT pools to evaluate the impact of PI on growth factor concentration and capacity to sustain cell growth. Additional PI-PL lots were used for comparison with fetal bovine serum (FBS) on MSC expansion. Immunoregulatory properties of PI-PL-generated MSC were documented in vitro by mixed lymphocyte culture (MLC) and peripheral blood mononuclear cells (PBMC) mitogen induced proliferation. Results PI-PL and PL control lots had similar concentrations of 4 well-described growth factors endowed with MSC stimulating ability. Initial growth and MSC expansion by PI-PL and PL controls were comparable either using different MSC populations or in head to head experiments. Moreover, PI-PL and PL control sustained similar MSC growth of frozen/thawed MSC. Multilineage differentiation of PI-derived and PI-PL-derived MSC were maintained in any MSC cultures as well as their immunoregulatory properties. Finally, no direct impact of PI on growth factor concentration and MSC growth support was observed, whereas the capacity of FBS to sustain MSC expansion in basic medium was irrelevant as compared to PL and PI-PL. Conclusion The replacement of animal additives with human supplements is a basic issue in MSC ex vivo production. PI-PL represents a standardized, plasma-poor, human preparation which appears as a safe and good candidate to stimulate MSC growth in clinical-scale cultures. PMID:24467837
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NASA Astrophysics Data System (ADS)
Bootsma, Gregory J.
X-ray scatter in cone-beam computed tomography (CBCT) is known to reduce image quality by introducing image artifacts, reducing contrast, and limiting computed tomography (CT) number accuracy. The extent of the effect of x-ray scatter on CBCT image quality is determined by the shape and magnitude of the scatter distribution in the projections. A method to allay the effects of scatter is imperative to enable application of CBCT to solve a wider domain of clinical problems. The work contained herein proposes such a method. A characterization of the scatter distribution through the use of a validated Monte Carlo (MC) model is carried out. The effects of imaging parameters and compensators on the scatter distribution are investigated. The spectral frequency components of the scatter distribution in CBCT projection sets are analyzed using Fourier analysis and found to reside predominately in the low frequency domain. The exact frequency extents of the scatter distribution are explored for different imaging configurations and patient geometries. Based on the Fourier analysis it is hypothesized the scatter distribution can be represented by a finite sum of sine and cosine functions. The fitting of MC scatter distribution estimates enables the reduction of the MC computation time by diminishing the number of photon tracks required by over three orders of magnitude. The fitting method is incorporated into a novel scatter correction method using an algorithm that simultaneously combines multiple MC scatter simulations. Running concurrent MC simulations while simultaneously fitting the results allows for the physical accuracy and flexibility of MC methods to be maintained while enhancing the overall efficiency. CBCT projection set scatter estimates, using the algorithm, are computed on the order of 1--2 minutes instead of hours or days. Resulting scatter corrected reconstructions show a reduction in artifacts and improvement in tissue contrast and voxel value accuracy.
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Ronsyn, Mark W; Daans, Jasmijn; Spaepen, Gie; Chatterjee, Shyama; Vermeulen, Katrien; D'Haese, Patrick; Van Tendeloo, Viggo FI; Van Marck, Eric; Ysebaert, Dirk; Berneman, Zwi N; Jorens, Philippe G; Ponsaerts, Peter
2007-01-01
Background Bone marrow-derived stromal cells (MSC) are attractive targets for ex vivo cell and gene therapy. In this context, we investigated the feasibility of a plasmid-based strategy for genetic modification of human (h)MSC with enhanced green fluorescent protein (EGFP) and neurotrophin (NT)3. Three genetically modified hMSC lines (EGFP, NT3, NT3-EGFP) were established and used to study cell survival and transgene expression following transplantation in rat spinal cord. Results First, we demonstrate long-term survival of transplanted hMSC-EGFP cells in rat spinal cord under, but not without, appropriate immune suppression. Next, we examined the stability of EGFP or NT3 transgene expression following transplantation of hMSC-EGFP, hMSC-NT3 and hMSC-NT3-EGFP in rat spinal cord. While in vivo EGFP mRNA and protein expression by transplanted hMSC-EGFP cells was readily detectable at different time points post-transplantation, in vivo NT3 mRNA expression by hMSC-NT3 cells and in vivo EGFP protein expression by hMSC-NT3-EGFP cells was, respectively, undetectable or declined rapidly between day 1 and 7 post-transplantation. Further investigation revealed that the observed in vivo decline of EGFP protein expression by hMSC-NT3-EGFP cells: (i) was associated with a decrease in transgenic NT3-EGFP mRNA expression as suggested following laser capture micro-dissection analysis of hMSC-NT3-EGFP cell transplants at day 1 and day 7 post-transplantation, (ii) did not occur when hMSC-NT3-EGFP cells were transplanted subcutaneously, and (iii) was reversed upon re-establishment of hMSC-NT3-EGFP cell cultures at 2 weeks post-transplantation. Finally, because we observed a slowly progressing tumour growth following transplantation of all our hMSC cell transplants, we here demonstrate that omitting immune suppressive therapy is sufficient to prevent further tumour growth and to eradicate malignant xenogeneic cell transplants. Conclusion In this study, we demonstrate that genetically modified hMSC lines can survive in healthy rat spinal cord over at least 3 weeks by using adequate immune suppression and can serve as vehicles for transgene expression. However, before genetically modified hMSC can potentially be used in a clinical setting to treat spinal cord injuries, more research on standardisation of hMSC culture and genetic modification needs to be done in order to prevent tumour formation and transgene silencing in vivo. PMID:18078525
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Ronsyn, Mark W; Daans, Jasmijn; Spaepen, Gie; Chatterjee, Shyama; Vermeulen, Katrien; D'Haese, Patrick; Van Tendeloo, Viggo Fi; Van Marck, Eric; Ysebaert, Dirk; Berneman, Zwi N; Jorens, Philippe G; Ponsaerts, Peter
2007-12-14
Bone marrow-derived stromal cells (MSC) are attractive targets for ex vivo cell and gene therapy. In this context, we investigated the feasibility of a plasmid-based strategy for genetic modification of human (h)MSC with enhanced green fluorescent protein (EGFP) and neurotrophin (NT)3. Three genetically modified hMSC lines (EGFP, NT3, NT3-EGFP) were established and used to study cell survival and transgene expression following transplantation in rat spinal cord. First, we demonstrate long-term survival of transplanted hMSC-EGFP cells in rat spinal cord under, but not without, appropriate immune suppression. Next, we examined the stability of EGFP or NT3 transgene expression following transplantation of hMSC-EGFP, hMSC-NT3 and hMSC-NT3-EGFP in rat spinal cord. While in vivo EGFP mRNA and protein expression by transplanted hMSC-EGFP cells was readily detectable at different time points post-transplantation, in vivo NT3 mRNA expression by hMSC-NT3 cells and in vivo EGFP protein expression by hMSC-NT3-EGFP cells was, respectively, undetectable or declined rapidly between day 1 and 7 post-transplantation. Further investigation revealed that the observed in vivo decline of EGFP protein expression by hMSC-NT3-EGFP cells: (i) was associated with a decrease in transgenic NT3-EGFP mRNA expression as suggested following laser capture micro-dissection analysis of hMSC-NT3-EGFP cell transplants at day 1 and day 7 post-transplantation, (ii) did not occur when hMSC-NT3-EGFP cells were transplanted subcutaneously, and (iii) was reversed upon re-establishment of hMSC-NT3-EGFP cell cultures at 2 weeks post-transplantation. Finally, because we observed a slowly progressing tumour growth following transplantation of all our hMSC cell transplants, we here demonstrate that omitting immune suppressive therapy is sufficient to prevent further tumour growth and to eradicate malignant xenogeneic cell transplants. In this study, we demonstrate that genetically modified hMSC lines can survive in healthy rat spinal cord over at least 3 weeks by using adequate immune suppression and can serve as vehicles for transgene expression. However, before genetically modified hMSC can potentially be used in a clinical setting to treat spinal cord injuries, more research on standardisation of hMSC culture and genetic modification needs to be done in order to prevent tumour formation and transgene silencing in vivo.
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Inflight - Apollo XI (Mission Control Center [MCC]) - MSC
1969-07-24
S69-40302 (24 July 1969) --- A group of NASA and Manned Spacecraft Center (MSC) officials join in with the flight controllers in the Mission Operations Control Room (MOCR) in the Mission Control Center (MCC), Building 30, in celebrating the successful conclusion of the Apollo 11 lunar landing mission. From left foreground are Dr. Maxime A. Faget, MSC Director of Engineering and Development; George S. Trimble, MSC Deputy Director; Dr. Christopher C. Kraft Jr., MSC Director of Flight Operations; Julian Scheer (in back), Assistant Administrator, Office of Public Affairs, NASA Headquarters; George M. Low, Manager, Apollo Spacecraft Program, MSC; Dr. Robert R. Gilruth, MSC Director; and Charles W. Mathews, Deputy Associate Administrator, Office of Manned Space Flight, NASA Headquarters.
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Non-cancellation of electroweak logarithms in high-energy scattering
Manohar, Aneesh V.; Shotwell, Brian; Bauer, Christian W.; ...
2015-01-01
We study electroweak Sudakov corrections in high energy scattering, and the cancellation between real and virtual Sudakov corrections. Numerical results are given for the case of heavy quark production by gluon collisions involving the rates gg→t¯t, b¯b, t¯bW, t¯tZ, b¯bZ, t¯tH, b¯bH. Gauge boson virtual corrections are related to real transverse gauge boson emission, and Higgs virtual corrections to Higgs and longitudinal gauge boson emission. At the LHC, electroweak corrections become important in the TeV regime. At the proposed 100TeV collider, electroweak interactions enter a new regime, where the corrections are very large and need to be resummed.
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Three MSC officials hold discussion in Mission Control room during Gemini 11
1966-09-12
S66-52754 (12 Sept. 1966) --- Three key Manned Spacecraft Center (MSC) officials hold discussion in the Mission Control room during Gemini-11 activity. Left to right, are Donald K. Slayton, MSC Director of Flight Crew Operations; astronaut Alan B. Shepard Jr., Chief, MSC Astronaut Office; and George M. Low, MSC Deputy Director. Photo credit: NASA
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NASA Astrophysics Data System (ADS)
Xiong, Kun; Gao, Yuan; Zhou, Lin; Zhang, Xianming
2016-09-01
Nanoscale zero-valent iron (nZVI) particles were embedded on the walls of mesoporous silica-carbon (MSC) under the conditions of high-temperature carbonization and reduction and used to remove chromium (VI) from aqueous solution. The structure and textural properties of nZVI-MSC were characterized by the powder X-ray diffraction, transmission electron microscopy and N2 adsorption and desorption. The results show that nZVI-MSC has highly ordered mesoporous structure and large surface area, indistinguishable with that of MSC. Compared with the support MSC and iron particles supported on the activated carbon (nZVI/AC), nZVI-MSC exhibited much higher Cr(VI) removal efficiency with about 98 %. The removal process obeys a pseudo first-order model. Such excellent performance of nZVI-MSC could be ascribed to the large surface and iron particles embedded on the walls of the MSC, forming an intimate contact with the MSC. It is proposed that this feature might create certain micro-electrode on the interface of iron particles and MSC, which prevented the formation of metal oxide on the surface and provided fresh Fe surface for Cr(VI) removal.
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Zou, Xiangyu; Jiang, Kai; Puranik, Amrutesh S; Jordan, Kyra L; Tang, Hui; Zhu, Xiangyang; Lerman, Lilach O
2018-05-01
Mesenchymal stem cells (MSC) have been experimentally used for kidney repair, but modest retention limits their efficacy. Cell-surface coating allows modulating MSC homing and interaction with target cells. We coated mouse adipose tissue-derived MSC with antibodies directed against kidney injury molecule-1 (ab-KIM1), which is upregulated in injured kidneys, and tested the hypothesis that this would enhance their therapeutic effects in ischemic kidney injury. Untreated MSC, ab-KIM1-coated MSC (KIM-MSC), or vehicle, were injected systemically into the carotid artery of 2-kidneys, 1-clip mice 2 weeks after surgery. MSC retention in different organs was explored 24 hours, 48 hours, or 2 weeks after injection. Renal volume, perfusion, and oxygenation were studied 2 weeks after injection using magnetic resonance imaging in vivo, and renal inflammation, apoptosis, capillary density, and fibrosis ex vivo. The ab-KIM1 coating had little effect on MSC viability or proliferation. The stenotic kidney showed upregulated KIM1 expression, selective homing, and greater retention of KIM-MSC compared to untreated MSC and compared to other organs. KIM-MSC-injected mice improved renal perfusion and capillary density, and attenuated oxidative damage, apoptosis, and fibrosis compared to mice treated with vehicle or with native MSC. In conclusion, MSC coating with ab-KIM1 increased their retention in the ischemic kidney and enhanced their therapeutic efficacy. This novel method may be useful to selectively target injured kidneys, and supports further development of strategies to enhance cell-based treatment of ischemic kidney injury. Stem Cells Translational Medicine 2018;7:394-403. © 2018 The Authors Stem Cells Translational Medicine published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Wu, Jiamin; Wu, Kewen; Lin, Feng
2013-11-08
Highlights: •MGF induced the migration of rat MSC in a concentration-dependent manner. •MGF enhanced the mechanical properties of rMSC in inducing its migration. •MGF activated the ERK 1/2 signaling pathway of rMSC in inducing its migration. •rMSC mechanics may synergy with ERK 1/2 pathway in MGF-induced rMSC migration. -- Abstract: Mechano-growth factor (MGF) generated by cells in response to mechanical stimulation has been identified as a mechano effector molecule, playing a key role in regulating mesenchymal stem cell (MSC) function, including proliferation and migration. However, the mechanism(s) underlying how MGF-induced MSC migration occurs is still unclear. In the present study,more » MGF motivated migration of rat MSCs (rMSCs) in a concentration-dependent manner and optimal concentration of MGF at 50 ng/mL (defined as MGF treatment in this paper) was demonstrated. Notably, enhancement of mechanical properties that is pertinent to cell migration, such as cell traction force and cell stiffness were found to respond to MGF treatment. Furthermore, MGF increased phosphorylation of extracellular signal-regulated kinase (ERK), ERK inhibitor (i.e., PD98059) suppressed ERK phosphorylation, and abolished MGF-induced rMSC migration were found, demonstrating that ERK is involved molecule for MGF-induced rMSC migration. These in vitro evidences of MGF-induced rMSC migration and its direct link to altering rMSC mechanics and activating the ERK pathway, uncover the underlying biomechanical and biological mechanisms of MGF-induced rMSC migration, which may help find MGF-based application of MSC in clinical therapeutics.« less
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Anti-Inflammatory Effects of Adult Stem Cells in Sustained Lung Injury: A Comparative Study
Moodley, Yuben; Vaghjiani, Vijesh; Chan, James; Baltic, Svetlana; Ryan, Marisa; Tchongue, Jorge; Samuel, Chrishan S.; Murthi, Padma; Parolini, Ornella; Manuelpillai, Ursula
2013-01-01
Lung diseases are a major cause of global morbidity and mortality that are treated with limited efficacy. Recently stem cell therapies have been shown to effectively treat animal models of lung disease. However, there are limitations to the translation of these cell therapies to clinical disease. Studies have shown that delayed treatment of animal models does not improve outcomes and that the models do not reflect the repeated injury that is present in most lung diseases. We tested the efficacy of amnion mesenchymal stem cells (AM-MSC), bone marrow MSC (BM-MSC) and human amniotic epithelial cells (hAEC) in C57BL/6 mice using a repeat dose bleomycin-induced model of lung injury that better reflects the repeat injury seen in lung diseases. The dual bleomycin dose led to significantly higher levels of inflammation and fibrosis in the mouse lung compared to a single bleomycin dose. Intravenously infused stem cells were present in the lung in similar numbers at days 7 and 21 post cell injection. In addition, stem cell injection resulted in a significant decrease in inflammatory cell infiltrate and a reduction in IL-1 (AM-MSC), IL-6 (AM-MSC, BM-MSC, hAEC) and TNF-α (AM-MSC). The only trophic factor tested that increased following stem cell injection was IL-1RA (AM-MSC). IL-1RA levels may be modulated by GM-CSF produced by AM-MSC. Furthermore, only AM-MSC reduced collagen deposition and increased MMP-9 activity in the lung although there was a reduction of the pro-fibrogenic cytokine TGF-β following BM-MSC, AM-MSC and hAEC treatment. Therefore, AM-MSC may be more effective in reducing injury following delayed injection in the setting of repeated lung injury. PMID:23936322
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Mesenchymal Stromal Cell Therapy in Crohn's Disease.
Forbes, Geoffrey M
2017-01-01
Mesenchymal stromal cells (MSC) are multipotent adult stem cells with immunomodulatory properties. They uniquely express HLA class I antigen at a low level, and do not express HLA class II. Hence, for allogeneic administration, donor to recipient matching is not required; yet a prolonged chimeric state does not occur. Contrary to haematopoietic stem cell transplantation, cytotoxic drug therapy is not required to harvest, or administer, cells. Key Messages: MSC are obtained from marrow, adipose tissue or placenta. In our centre, MSC are isolated from a 10 ml donor marrow aspirate, by virtue of their adherence to plastic. They are expanded in culture, cryopreserved, and subjected to strict quality controls before release for intravenous administration. These activities occur in a dedicated, nationally accredited, laboratory. Initial observations of allogeneic MSC efficacy were in graft-versus-host disease. Both autologous and allogeneic MSC have since been evaluated in biologic refractory luminal and fistulising Crohn's disease (CD). Data from early-phase studies have suggested efficacy for luminal disease when allogeneic MSC were given intravenously and also suggested efficacy for fistulising disease when either allogeneic or autologous MSC were administered into fistulas. MSC treatment is not reported to have caused serious adverse events. Although in vitro criteria for defining MSC exist, a major challenge lies in how to define MSC for clinical use. MSC function in vivo is likely to be dependent upon donor immunological characteristics, and widely varying manufacturing processes between laboratories. MSC dose, frequency of administration, stage of disease, and presence of concomitant immunosuppression also require to be defined. MSC therapy may have future utility in CD, but considerable work is first required to determine appropriate phenotypic and functional characteristics of administered cells. © 2017 S. Karger AG, Basel.
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Chu, Pat P. Y.; Bari, Sudipto; Fan, Xiubo; Gay, Florence P. H.; Ang, Justina M. L.; Chiu, Gigi N. C.; Lim, Sai K.; Hwang, William Y. K.
2012-01-01
Background aims. Mesenchymal stromal cells (MSC) have been observed to participate in tissue repair and to have growth-promoting effects on ex vivo co-culture with other stem cells. Methods. In order to evaluate the mechanism of MSC support on ex vivo cultures, we performed co-culture of MSC with umbilical cord blood (UCB) mononuclear cells (MNC) (UCB-MNC). Results. Significant enhancement in cell growth correlating with cell viability was noted with MSC co-culture (defined by double-negative staining for Annexin-V and 7-AAD; P<0.01). This was associated with significant enhancement of mitochondrial membrane potential (P<0.01). We postulated that intercellular transfer of cytosolic substances between MSC and UCB-MNC could be one mechanism mediating the support. Using MSC endogenously expressing green fluorescent protein (GFP) or labeled with quantum dots (QD), we performed co-culture of UCB-MNC with these MSC. Transfer of these GFP and QD was observed from MSC to UCB-MNC as early as 24 h post co-culture. Transwell experiments revealed that direct contact between MSC and UCB-MNC was necessary for both transfer and viability support. UCB-MNC tightly adherent to the MSC layer exhibited the most optimal transfer and rescue of cell viability. DNA analysis of the viable, GFP transfer-positive UCB-MNC ruled out MSC transdifferentiation or MSC-UCB fusion. In addition, there was statistical correlation between higher levels of cytosolic transfer and enhanced UCB-MNC viability (P< 0.0001). Conclusions. Collectively, the data suggest that intercellular transfer of cytosolic materials could be one novel mechanism for preventing UCB cell death in MSC co-culture. PMID:22775077
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Modeling boundary measurements of scattered light using the corrected diffusion approximation
Lehtikangas, Ossi; Tarvainen, Tanja; Kim, Arnold D.
2012-01-01
We study the modeling and simulation of steady-state measurements of light scattered by a turbid medium taken at the boundary. In particular, we implement the recently introduced corrected diffusion approximation in two spatial dimensions to model these boundary measurements. This implementation uses expansions in plane wave solutions to compute boundary conditions and the additive boundary layer correction, and a finite element method to solve the diffusion equation. We show that this corrected diffusion approximation models boundary measurements substantially better than the standard diffusion approximation in comparison to numerical solutions of the radiative transport equation. PMID:22435102
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Quadratic electroweak corrections for polarized Moller scattering
DOE Office of Scientific and Technical Information (OSTI.GOV)
A. Aleksejevs, S. Barkanova, Y. Kolomensky, E. Kuraev, V. Zykunov
2012-01-01
The paper discusses the two-loop (NNLO) electroweak radiative corrections to the parity violating electron-electron scattering asymmetry induced by squaring one-loop diagrams. The calculations are relevant for the ultra-precise 11 GeV MOLLER experiment planned at Jefferson Laboratory and experiments at high-energy future electron colliders. The imaginary parts of the amplitudes are taken into consideration consistently in both the infrared-finite and divergent terms. The size of the obtained partial correction is significant, which indicates a need for a complete study of the two-loop electroweak radiative corrections in order to meet the precision goals of future experiments.
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Library based x-ray scatter correction for dedicated cone beam breast CT
DOE Office of Scientific and Technical Information (OSTI.GOV)
Shi, Linxi; Zhu, Lei, E-mail: leizhu@gatech.edu
Purpose: The image quality of dedicated cone beam breast CT (CBBCT) is limited by substantial scatter contamination, resulting in cupping artifacts and contrast-loss in reconstructed images. Such effects obscure the visibility of soft-tissue lesions and calcifications, which hinders breast cancer detection and diagnosis. In this work, we propose a library-based software approach to suppress scatter on CBBCT images with high efficiency, accuracy, and reliability. Methods: The authors precompute a scatter library on simplified breast models with different sizes using the GEANT4-based Monte Carlo (MC) toolkit. The breast is approximated as a semiellipsoid with homogeneous glandular/adipose tissue mixture. For scatter correctionmore » on real clinical data, the authors estimate the breast size from a first-pass breast CT reconstruction and then select the corresponding scatter distribution from the library. The selected scatter distribution from simplified breast models is spatially translated to match the projection data from the clinical scan and is subtracted from the measured projection for effective scatter correction. The method performance was evaluated using 15 sets of patient data, with a wide range of breast sizes representing about 95% of general population. Spatial nonuniformity (SNU) and contrast to signal deviation ratio (CDR) were used as metrics for evaluation. Results: Since the time-consuming MC simulation for library generation is precomputed, the authors’ method efficiently corrects for scatter with minimal processing time. Furthermore, the authors find that a scatter library on a simple breast model with only one input parameter, i.e., the breast diameter, sufficiently guarantees improvements in SNU and CDR. For the 15 clinical datasets, the authors’ method reduces the average SNU from 7.14% to 2.47% in coronal views and from 10.14% to 3.02% in sagittal views. On average, the CDR is improved by a factor of 1.49 in coronal views and 2.12 in sagittal views. Conclusions: The library-based scatter correction does not require increase in radiation dose or hardware modifications, and it improves over the existing methods on implementation simplicity and computational efficiency. As demonstrated through patient studies, the authors’ approach is effective and stable, and is therefore clinically attractive for CBBCT imaging.« less
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Shi, L; Zhu, L; Vedantham, S
2016-06-15
Purpose: The image quality of dedicated cone-beam breast CT (CBBCT) is fundamentally limited by substantial x-ray scatter contamination, resulting in cupping artifacts and contrast-loss in reconstructed images. Such effects obscure the visibility of soft-tissue lesions and calcifications, which hinders breast cancer detection and diagnosis. In this work, we propose to suppress x-ray scatter in CBBCT images using a deterministic forward projection model. Method: We first use the 1st-pass FDK-reconstructed CBBCT images to segment fibroglandular and adipose tissue. Attenuation coefficients are assigned to the two tissues based on the x-ray spectrum used for imaging acquisition, and is forward projected to simulatemore » scatter-free primary projections. We estimate the scatter by subtracting the simulated primary projection from the measured projection, and then the resultant scatter map is further refined by a Fourier-domain fitting algorithm after discarding untrusted scatter information. The final scatter estimate is subtracted from the measured projection for effective scatter correction. In our implementation, the proposed scatter correction takes 0.5 seconds for each projection. The method was evaluated using the overall image spatial non-uniformity (SNU) metric and the contrast-to-noise ratio (CNR) with 5 clinical datasets of BI-RADS 4/5 subjects. Results: For the 5 clinical datasets, our method reduced the SNU from 7.79% to 1.68% in coronal view and from 6.71% to 3.20% in sagittal view. The average CNR is improved by a factor of 1.38 in coronal view and 1.26 in sagittal view. Conclusion: The proposed scatter correction approach requires no additional scans or prior images and uses a deterministic model for efficient calculation. Evaluation with clinical datasets demonstrates the feasibility and stability of the method. These features are attractive for clinical CBBCT and make our method distinct from other approaches. Supported partly by NIH R21EB019597, R21CA134128 and R01CA195512.The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.« less
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NASA Astrophysics Data System (ADS)
Oelze, Michael L.; O'Brien, William D.
2004-11-01
Backscattered rf signals used to construct conventional ultrasound B-mode images contain frequency-dependent information that can be examined through the backscattered power spectrum. The backscattered power spectrum is found by taking the magnitude squared of the Fourier transform of a gated time segment corresponding to a region in the scattering volume. When a time segment is gated, the edges of the gated regions change the frequency content of the backscattered power spectrum due to truncating of the waveform. Tapered windows, like the Hanning window, and longer gate lengths reduce the relative contribution of the gate-edge effects. A new gate-edge correction factor was developed that partially accounted for the edge effects. The gate-edge correction factor gave more accurate estimates of scatterer properties at small gate lengths compared to conventional windowing functions. The gate-edge correction factor gave estimates of scatterer properties within 5% of actual values at very small gate lengths (less than 5 spatial pulse lengths) in both simulations and from measurements on glass-bead phantoms. While the gate-edge correction factor gave higher accuracy of estimates at smaller gate lengths, the precision of estimates was not improved at small gate lengths over conventional windowing functions. .
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Generalized model screening potentials for Fermi-Dirac plasmas
NASA Astrophysics Data System (ADS)
Akbari-Moghanjoughi, M.
2016-04-01
In this paper, some properties of relativistically degenerate quantum plasmas, such as static ion screening, structure factor, and Thomson scattering cross-section, are studied in the framework of linearized quantum hydrodynamic theory with the newly proposed kinetic γ-correction to Bohm term in low frequency limit. It is found that the correction has a significant effect on the properties of quantum plasmas in all density regimes, ranging from solid-density up to that of white dwarf stars. It is also found that Shukla-Eliasson attractive force exists up to a few times the density of metals, and the ionic correlations are seemingly apparent in the radial distribution function signature. Simplified statically screened attractive and repulsive potentials are presented for zero-temperature Fermi-Dirac plasmas, valid for a wide range of quantum plasma number-density and atomic number values. Moreover, it is observed that crystallization of white dwarfs beyond a critical core number-density persists with this new kinetic correction, but it is shifted to a much higher number-density value of n0 ≃ 1.94 × 1037 cm-3 (1.77 × 1010 gr cm-3), which is nearly four orders of magnitude less than the nuclear density. It is found that the maximal Thomson scattering with the γ-corrected structure factor is a remarkable property of white dwarf stars. However, with the new γ-correction, the maximal scattering shifts to the spectrum region between hard X-ray and low-energy gamma-rays. White dwarfs composed of higher atomic-number ions are observed to maximally Thomson-scatter at slightly higher wavelengths, i.e., they maximally scatter slightly low-energy photons in the presence of correction.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Hall, Nathan L.; Blunden, Peter G.; Melnitchouk, Wally
2015-12-08
We examine the interference \\gamma Z box corrections to parity-violating elastic electron--proton scattering in the light of the recent observation of quark-hadron duality in parity-violating deep-inelastic scattering from the deuteron, and the approximate isospin independence of duality in the electromagnetic nucleon structure functions down to Q 2 \\approx 1 GeV 2. Assuming that a similar behavior also holds for the \\gamma Z proton structure functions, we find that duality constrains the γ Z box correction to the proton's weak charge to be Re V γ Z V = (5.4 \\pm 0.4) \\times 10 -3 at the kinematics of the Qmore » weak experiment. Within the same model we also provide estimates of the γ Z corrections for future parity-violating experiments, such as MOLLER at Jefferson Lab and MESA at Mainz.« less
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Burastero, Giorgio; Scarfì, Sonia; Ferraris, Chiara; Fresia, Chiara; Sessarego, Nadia; Fruscione, Floriana; Monetti, Francesco; Scarfò, Francesca; Schupbach, Peter; Podestà, Marina; Grappiolo, Guido; Zocchi, Elena
2010-07-01
Critical size segmental bone defects are still a major challenge in reconstructive orthopedic surgery. Transplantation of human mesenchymal stem cells (hMSC) has been proposed as an alternative to autogenous bone graft, as MSC can be expanded in vitro and induced to differentiate into bone-regenerating osteoblasts by several bone morphogenetic proteins (BMP). The aim of this study was to investigate whether the association of hMSC and BMP-7, with providing the necessary scaffold to fill the bone loss, improved bone regeneration in a rat model of critical size segmental bone defect, compared to treatment with either hMSC or BMP-7 and the matrix. In addition, we tested whether pre-treatment of hMSC with cyclic ADP-ribose (cADPR), an intracellular Ca2+ mobilizer previously shown to accelerate the in vitro expansion of hMSC (Scarfì S et al, Stem Cells, 2008), affected the osteoinductive capacity of the cells in vivo. X-ray analysis, performed 2, 10 and 16 weeks after transplantation, revealed a significantly higher score in the rats treated with hMSC and BMP-7 compared to controls, receiving either hMSC or BMP-7. Microtomography and histological analysis, performed 16weeks after transplantation, confirmed the improved bone regeneration in the animals treated with the association of hMSC and BMP-7 compared to controls. Pre-treatment with cADPR to stimulate hMSC proliferation in vitro did not affect the bone regenerating capacity of the cells in vivo. These results indicate that the association of in vitro expanded hMSC with BMP-7 provide a better osteoinductive graft compared to either hMSC or BMP-7 alone. Moreover, cADPR may be used to stimulate hMSC proliferation in vitro in order to reduce the time required to obtain a transplantable number of cells, with no adverse effect on the bone regenerating capacity of hMSC. 2010 Elsevier Inc. All rights reserved.
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Rosová, Ivana; Dao, Mo; Capoccia, Ben; Link, Daniel; Nolta, Jan A.
2010-01-01
Mesenchymal stem cells (MSC) are adult multipotent cells found in bone marrow, adipose tissue, and other adult tissues. MSC have been shown to improve regeneration of injured tissues in vivo, but the mechanisms remain unclear. Typically, MSC are cultured under ambient, or normoxic, conditions (21% oxygen). However, the physiological niches for MSC in the bone marrow and other sites have much lower oxygen tension. When used as a therapeutic tool to repair tissue injuries, MSC cultured in standard conditions must adapt from 21% oxygen in culture to less than 1% oxygen in the ischemic tissue. We therefore examined the effects of preculturing human bone marrow-derived MSC in hypoxic conditions (1%–3% oxygen) to elucidate the best conditions that enhance their tissue regenerative potential. We demonstrated that MSC cultured in hypoxia activate the Akt signaling pathway while maintaining their viability and cell cycle rates. We also showed that MSC cultured in hypoxia induced expression of cMet, the major receptor for hepatocyte growth factor (HGF), and enhanced cMet signaling. MSC cultured in hypoxic conditions increased their migration rates. Since migration and HGF responsiveness are thought to be key mediators of MSC recruitment and/or activation in vivo, we next examined the tissue regenerative potential of MSC cultured under hypoxic conditions, using a murine hind limb ischemia model. We showed that local expression of HGF is increased in ischemic muscle in this model. Intra-arterial injection of MSC cultured in either normoxic or hypoxic conditions 24 hours after surgical induction of hind limb ischemia enhanced revascularization compared with saline controls. However, restoration of blood flow was observed significantly earlier in mice that had been injected with hypoxic preconditioned MSC. Collectively, these data suggest that preculturing MSC under hypoxic conditions prior to transplantation improves their tissue regenerative potential. PMID:18511601
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Kawai, Takamasa; Katagiri, Wataru; Osugi, Masashi; Sugimura, Yukiko; Hibi, Hideharu; Ueda, Minoru
2015-04-01
Periodontal tissue regeneration with the use of mesenchymal stromal cells (MSCs) has been regarded as a future cell-based therapy. However, low survival rates and the potential tumorigenicity of implanted MSCs could undermine the efficacy of cell-based therapy. The use of conditioned media from MSCs (MSC-CM) may be a feasible approach to overcome these limitations. The aim of this study was to confirm the effect of MSC-CM on periodontal regeneration. MSC-CM were collected during their cultivation. The concentrations of the growth factors in MSC-CM were measured with the use of enzyme-linked immunoassay. Rat MSCs (rMSCs) and human umbilical vein endothelial cells cultured in MSC-CM were assessed on wound-healing and angiogenesis. The expressions of osteogenetic- and angiogenic-related genes of rMSCs cultured in MSC-CM were quantified by means of real-time reverse transcriptase-polymerase chain reaction analysis. In vivo, periodontal defects were prepared in the rat models and the collagen sponges with MSC-CM were implanted. MSC-CM includes insulin-like growth factor-1, vascular endothelial growth factor, transforming growth factor-β1 and hepatocyte growth factor. In vitro, wound-healing and angiogenesis increased significantly in MSC-CM. The levels of expression of osteogenetic- and angiogenic-related genes were significantly upregulated in rMSCs cultured with MSC-CM. In vivo, in the MSC-CM group, 2 weeks after implantation, immunohistochemical analysis showed several CD31-, CD105-or FLK-1-positive cells occurring frequently. At 4 weeks after implantation, regenerated periodontal tissue was observed in MSC-CM groups. The use of MSC-CM may be an alternative therapy for periodontal tissue regeneration because several cytokines included in MSC-CM will contribute to many processes of complicated periodontal tissue regeneration. Copyright © 2015 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.
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Raicevic, Gordana; Najar, Mehdi; Pieters, Karlien; De Bruyn, Cecile; Meuleman, Nathalie; Bron, Dominique; Toungouz, Michel; Lagneaux, Laurence
2012-07-01
Mesenchymal stromal cells (MSCs) can be isolated not only from bone marrow (BM) but also from other tissues, including adipose tissue (AT) and umbilical cord Wharton's Jelly (WJ). Thanks to their ability to differentiate into various cell types, MSC are considered attractive candidates for cell-based regenerative therapy. In degenerative clinical settings, inflammation or infection is often involved. In the present work, we hypothesized that an inflammatory environment and/or Toll-like receptor (TLR) ligation could affect the MSC differentiation potential. MSC were isolated from BM, AT, and WJ. Inflammation was mimicked by a cytokine cocktail, and TLR activation was induced through TLR3 and TLR4 ligation. Osteogenesis was chosen as a model for differentiation. Osteogenic parameters were evaluated by measuring Ca2+ deposits and alkaline phosphatase (ALP) activity at day 7, 14, and 21 of the culture in an osteogenic medium. Our results show that WJ-MSC exhibit a much lower osteogenic potential than the other two MSC types. However, inflammation was able to strongly increase the osteogenic differentiation of WJ-MSC as calcification, and ALP activity appeared as early as day 7. However, this latter enzymatic activity remained much lower than that disclosed by BM-MSC. TLR3 or TLR4 triggering increased the osteogenesis in AT- and, to lesser extent, in BM-MSC. In conclusion, WJ-MSC constitutively disclose a lower osteogenic potential as compared with BM and AT-MSC, which is not affected by TLR triggering but is strongly increased by inflammation, then reaching the level of BM-MSC. These observations suggest that WJ-MSC could constitute an alternative of BM-MSC for bone regenerative applications, as WJ is an easy access source of large amounts of MSC that can effectively differentiate into osteoblasts in an inflammatory setting.
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Quantitation of tumor uptake with molecular breast imaging.
Bache, Steven T; Kappadath, S Cheenu
2017-09-01
We developed scatter and attenuation-correction techniques for quantifying images obtained with Molecular Breast Imaging (MBI) systems. To investigate scatter correction, energy spectra of a 99m Tc point source were acquired with 0-7-cm-thick acrylic to simulate scatter between the detector heads. System-specific scatter correction factor, k, was calculated as a function of thickness using a dual energy window technique. To investigate attenuation correction, a 7-cm-thick rectangular phantom containing 99m Tc-water simulating breast tissue and fillable spheres simulating tumors was imaged. Six spheres 10-27 mm in diameter were imaged with sphere-to-background ratios (SBRs) of 3.5, 2.6, and 1.7 and located at depths of 0.5, 1.5, and 2.5 cm from the center of the water bath for 54 unique tumor scenarios (3 SBRs × 6 sphere sizes × 3 depths). Phantom images were also acquired in-air under scatter- and attenuation-free conditions, which provided ground truth counts. To estimate true counts, T, from each tumor, the geometric mean (GM) of the counts within a prescribed region of interest (ROI) from the two projection images was calculated as T=C1C2eμtF, where C are counts within the square ROI circumscribing each sphere on detectors 1 and 2, μ is the linear attenuation coefficient of water, t is detector separation, and the factor F accounts for background activity. Four unique F definitions-standard GM, background-subtraction GM, MIRD Primer 16 GM, and a novel "volumetric GM"-were investigated. Error in T was calculated as the percentage difference with respect to in-air. Quantitative accuracy using the different GM definitions was calculated as a function of SBR, depth, and sphere size. Sensitivity of quantitative accuracy to ROI size was investigated. We developed an MBI simulation to investigate the robustness of our corrections for various ellipsoidal tumor shapes and detector separations. Scatter correction factor k varied slightly (0.80-0.95) over a compressed breast thickness range of 6-9 cm. Corrected energy spectra recovered general characteristics of scatter-free spectra. Quantitatively, photopeak counts were recovered to <10% compared to in-air conditions after scatter correction. After GM attenuation correction, mean errors (95% confidence interval, CI) for all 54 imaging scenarios were 149% (-154% to +455%), -14.0% (-38.4% to +10.4%), 16.8% (-14.7% to +48.2%), and 2.0% (-14.3 to +18.3%) for the standard GM, background-subtraction GM, MIRD 16 GM, and volumetric GM, respectively. Volumetric GM was less sensitive to SBR and sphere size, while all GM methods were insensitive to sphere depth. Simulation results showed that Volumetric GM method produced a mean error within 5% over all compressed breast thicknesses (3-14 cm), and that the use of an estimated radius for nonspherical tumors increases the 95% CI to at most ±23%, compared with ±16% for spherical tumors. Using DEW scatter- and our Volumetric GM attenuation-correction methodology yielded accurate estimates of tumor counts in MBI over various tumor sizes, shapes, depths, background uptake, and compressed breast thicknesses. Accurate tumor uptake can be converted to radiotracer uptake concentration, allowing three patient-specific metrics to be calculated for quantifying absolute uptake and relative uptake change for assessment of treatment response. © 2017 American Association of Physicists in Medicine.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Armesilla-Diaz, Alejandro, E-mail: aarmesilla@cib.csic.es; Elvira, Gema; Silva, Augusto
2009-12-10
Mesenchymal stem cells (MSC) have been extensively studied and gained wide popularity due to their therapeutic potential. Spontaneous transformation of MSC, from both human and murine origin, has been reported in many studies. MSC transformation depends on the culture conditions, the origin of the cells and the time on culture; however, the precise biological characteristics involved in this process have not been fully defined yet. In this study, we investigated the role of p53 in the biology and transformation of murine bone marrow (BM)-derived MSC. We demonstrate that the MSC derived from p53KO mice showed an augmented proliferation rate, amore » shorter doubling time and also morphologic and phenotypic changes, as compared to MSC derived from wild-type animals. Furthermore, the MSC devoid of p53 had an increased number of cells able to generate colonies. In addition, not only proliferation but also MSC differentiation is controlled by p53 since its absence modifies the speed of the process. Moreover, genomic instability, changes in the expression of c-myc and anchorage independent growth were also observed in p53KO MSC. In addition, the absence of p53 implicates the spontaneous transformation of MSC in long-term cultures. Our results reveal that p53 plays a central role in the biology of MSC.« less
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Evidence for Transfer of Membranes from Mesenchymal Stem Cells to HL-1 Cardiac Cells.
Boomsma, Robert A; Geenen, David L
2014-01-01
This study examined the interaction of mouse bone marrow mesenchymal stem cells (MSC) with cardiac HL-1 cells during coculture by fluorescent dye labeling and then flow cytometry. MSC were layered onto confluent HL-1 cell cultures in a 1 : 4 ratio. MSC gained gap junction permeant calcein from HL-1 cells after 4 hours which was partially reduced by oleamide. After 20 hours, 99% MSC gained calcein, unaffected by oleamide. Double-labeling HL-1 cells with calcein and the membrane dye DiO resulted in transfer of both calcein and DiO to MSC. When HL-1 cells were labeled with calcein and MSC with DiO, MSC gained calcein while HL-1 cells gained DiO. Very little fusion was observed since more than 90% Sca-1 positive MSC gained DiO from HL-1 cells while less than 9% gained gap junction impermeant CMFDA after 20 hours with no Sca-1 transfer to HL-1 cells. Time dependent transfer of membrane DiD was observed from HL-1 cells to MSC (100%) and vice versa (50%) after 20 hours with more limited transfer of CMFDA. These results demonstrate that MSC and HL-1 cells exchange membrane components which may account for some of the beneficial effect of MSC in the heart after myocardial infarction.
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Jiang, Wenqian; Tan, Youwen; Cai, Mengjie; Zhao, Ting; Mao, Fei; Zhang, Xu; Xu, Wenrong; Yan, Zhixin; Qian, Hui; Yan, Yongmin
2018-01-01
Mesenchymal stem cells (MSCs) have been increasingly applied into clinical therapy. Exosomes are small (30-100 nm in diameter) membrane vesicles released by different cell types and possess the similar functions with their derived cells. Human umbilical cord MSC-derived exosomes (hucMSC-Ex) play important roles in liver repair. However, the effects and mechanisms of hucMSC-Ex on liver injury development remain elusive. Mouse models of acute and chronic liver injury and liver tumor were induced by carbon tetrachloride (CCl 4 ) injection, followed by administration of hucMSC-Ex via the tail vein. Alleviation of liver injury by hucMSC-Ex was determined. We further explored the production of oxidative stress and apoptosis in the development of liver injury and compared the antioxidant effects of hucMSC-Ex with frequently used hepatic protectant, bifendate (DDB) in liver injury. hucMSC-Ex alleviated CCl 4 -induced acute liver injury and liver fibrosis and restrained the growth of liver tumors. Decreased oxidative stress and apoptosis were found in hucMSC-Ex-treated mouse models and liver cells. Compared to bifendate (DDB) treatment, hucMSC-Ex presented more distinct antioxidant and hepatoprotective effects. hucMSC-Ex may suppress CCl 4 -induced liver injury development via antioxidant potentials and could be a more effective antioxidant than DDB in CCl 4 -induced liver tumor development.
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Novel application of stem cell-derived factors for periodontal regeneration
DOE Office of Scientific and Technical Information (OSTI.GOV)
Inukai, Takeharu, E-mail: t-inukai@med.nagoya-u.ac.jp; Katagiri, Wataru, E-mail: w-kat@med.nagoya-u.ac.jp; Yoshimi, Ryoko, E-mail: lianzi@med.nagoya-u.ac.jp
Highlights: Black-Right-Pointing-Pointer Mesenchymal stem cells (MSCs) secrete a variety of cytokines. Black-Right-Pointing-Pointer Cytokines were detected in conditioned medium from cultured MSCs (MSC-CM). Black-Right-Pointing-Pointer MSC-CM enhanced activation of dog MSCs and periodontal ligament cells. Black-Right-Pointing-Pointer MSC-CM significantly promoted alveolar bone and cementum regeneration. Black-Right-Pointing-Pointer Multiple cytokines contained in MSC-CM promote periodontal regeneration. -- Abstract: The effect of conditioned medium from cultured mesenchymal stem cells (MSC-CM) on periodontal regeneration was evaluated. In vitro, MSC-CM stimulated migration and proliferation of dog MSCs (dMSCs) and dog periodontal ligament cells (dPDLCs). Cytokines such as insulin-like growth factor, vascular endothelial growth factor, transforming growth factor-{beta}1, andmore » hepatocyte growth factor were detected in MSC-CM. In vivo, one-wall critical-size, intrabony periodontal defects were surgically created in the mandible of dogs. Dogs with these defects were divided into three groups that received MSC-CM, PBS, or no implants. Absorbable atelo-collagen sponges (TERUPLUG Registered-Sign ) were used as a scaffold material. Based on radiographic and histological observation 4 weeks after transplantation, the defect sites in the MSC-CM group displayed significantly greater alveolar bone and cementum regeneration than the other groups. These findings suggest that MSC-CM enhanced periodontal regeneration due to multiple cytokines contained in MSC-CM.« less
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Herzmann, Nicole; Salamon, Achim; Fiedler, Tomas
Mesenchymal stem cells (MSC) are able to stimulate the regeneration of injured tissue. Since bacterial infections are common complications in wound healing, bacterial pathogens and their components come into direct contact with MSC. The interaction with bacterial structures influences the proliferation, differentiation and migratory activity of the MSC, which might be of relevance during regeneration. Studies on MSC migration in response to bacterial components have shown different results depending on the cell type. Here, we analyzed the migration rate and chemotaxis of human adipose-derived MSC (adMSC) in response to the basic cell-wall components lipopolysaccharide (LPS) of Gram-negative bacteria and lipoteichoicmore » acid (LTA) of Gram-positive bacteria in vitro. To this end, we used transwell and scratch assays, as well as a specific chemotaxis assay combined with live-cell imaging. We found no significant influence of LPS or LTA on the migration rate of adMSC in transwell or scratch assays. Furthermore, in the µ-slide chemotaxis assay, the stimulation with LPS did not exert any chemotactic effect on adMSC. - Highlights: • LPS increased the release of IL-6 and IL-8 in adMSC significantly. • The migration rate of adMSC was not influenced by LPS or LTA. • LPS or LTA did not exert a chemotactic effect on adMSC.« less
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Song, Yingcai; Zhang, Bing; Guo, Fei; Yang, Maojun; Li, Yang; Liu, Zhi-Qiang
2017-01-01
The mechanosensitive channel of small conductance (MscS) is a bacterial membrane pore that senses membrane tension and protects cells from lysis by releasing osmolytes. MscS is a homoheptameric channel with a cytoplasmic domain with seven portals and a β-barrel opening to the cytoplasm. TtMscS, an MscS channel from Thermoanaerobacter tengcongensis, is an anion-selective channel. A previous study from our laboratory has defined the crucial role of β-barrel in the anion selectivity of TtMscS (Zhang et al., 2012). However, the mechanistic details by which the β-barrel determines anion selectivity remain unclear. Here, using mutagenesis and patch-clamp recordings, we investigated the function and structural correlations between β-barrels and the anion selectivity of TtMscS at the atomic level. Our results indicated that mutation of V274, a residue at the center of the inner wall of the β-barrel in TtMscS, caused the anion selectivity of TtMscS reverse to cation selectivity. Moreover, the electrostatic potential (T272) and physical size (L276) of residues in the inner wall of β-barrel also determine the anion selectivity of TtMscS. In summary, the present study confirmed that the β-barrel region of TtMscS acts as a “selective filter” that renders TtMscS anion selectivity. PMID:29118717
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Gao Hewei; Fahrig, Rebecca; Bennett, N. Robert
Purpose: Scatter correction is a major challenge in x-ray imaging using large area detectors. Recently, the authors proposed a promising scatter correction method for x-ray computed tomography (CT) using primary modulation. Proof of concept was previously illustrated by Monte Carlo simulations and physical experiments on a small phantom with a simple geometry. In this work, the authors provide a quantitative evaluation of the primary modulation technique and demonstrate its performance in applications where scatter correction is more challenging. Methods: The authors first analyze the potential errors of the estimated scatter in the primary modulation method. On two tabletop CT systems,more » the method is investigated using three phantoms: A Catphan(c)600 phantom, an anthropomorphic chest phantom, and the Catphan(c)600 phantom with two annuli. Two different primary modulators are also designed to show the impact of the modulator parameters on the scatter correction efficiency. The first is an aluminum modulator with a weak modulation and a low modulation frequency, and the second is a copper modulator with a strong modulation and a high modulation frequency. Results: On the Catphan(c)600 phantom in the first study, the method reduces the error of the CT number in the selected regions of interest (ROIs) from 371.4 to 21.9 Hounsfield units (HU); the contrast to noise ratio also increases from 10.9 to 19.2. On the anthropomorphic chest phantom in the second study, which represents a more difficult case due to the high scatter signals and object heterogeneity, the method reduces the error of the CT number from 327 to 19 HU in the selected ROIs and from 31.4% to 5.7% on the overall average. The third study is to investigate the impact of object size on the efficiency of our method. The scatter-to-primary ratio estimation error on the Catphan(c)600 phantom without any annulus (20 cm in diameter) is at the level of 0.04, it rises to 0.07 and 0.1 on the phantom with an elliptical annulus (30 cm in the minor axis and 38 cm in the major axis) and with a circular annulus (38 cm in diameter). Conclusions: On the three phantom studies, good scatter correction performance of the proposed method has been demonstrated using both image comparisons and quantitative analysis. The theory and experiments demonstrate that a strong primary modulation that possesses a low transmission factor and a high modulation frequency is preferred for high scatter correction accuracy.« less
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Retrieval of background surface reflectance with BRD components from pre-running BRDF
NASA Astrophysics Data System (ADS)
Choi, Sungwon; Lee, Kyeong-Sang; Jin, Donghyun; Lee, Darae; Han, Kyung-Soo
2016-10-01
Many countries try to launch satellite to observe the Earth surface. As important of surface remote sensing is increased, the reflectance of surface is a core parameter of the ground climate. But observing the reflectance of surface by satellite have weakness such as temporal resolution and being affected by view or solar angles. The bidirectional effects of the surface reflectance may make many noises to the time series. These noises can lead to make errors when determining surface reflectance. To correct bidirectional error of surface reflectance, using correction model for normalized the sensor data is necessary. A Bidirectional Reflectance Distribution Function (BRDF) is making accuracy higher method to correct scattering (Isotropic scattering, Geometric scattering, Volumetric scattering). To correct bidirectional error of surface reflectance, BRDF was used in this study. To correct bidirectional error of surface reflectance, we apply Bidirectional Reflectance Distribution Function (BRDF) to retrieve surface reflectance. And we apply 2 steps for retrieving Background Surface Reflectance (BSR). The first step is retrieving Bidirectional Reflectance Distribution (BRD) coefficients. Before retrieving BSR, we did pre-running BRDF to retrieve BRD coefficients to correct scatterings (Isotropic scattering, Geometric scattering, Volumetric scattering). In pre-running BRDF, we apply BRDF with observed surface reflectance of SPOT/VEGETATION (VGT-S1) and angular data to get BRD coefficients for calculating scattering. After that, we apply BRDF again in the opposite direction with BRD coefficients and angular data to retrieve BSR as a second step. As a result, BSR has very similar reflectance to one of VGT-S1. And reflectance in BSR is shown adequate. The highest reflectance of BSR is not over 0.4μm in blue channel, 0.45μm in red channel, 0.55μm in NIR channel. And for validation we compare reflectance of clear sky pixel from SPOT/VGT status map data. As a result of comparing BSR with VGT-S1, bias is from 0.0116 to 0.0158 and RMSE is from 0.0459 to 0.0545. They are very reasonable results, so we confirm that BSR is similar to VGT-S1. And weakness of this study is missing pixel in BSR which are observed less time to retrieve BRD components. If missing pixels are filled, BSR is better to retrieve surface products with more accuracy. And we think that after filling the missing pixel and being more accurate, it can be useful data to retrieve surface product which made by surface reflectance like cloud masking and retrieving aerosol.
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2013-01-01
Background Mesenchymal stem cells (MSC) can serve as carriers to deliver oncolytic measles virus (MV) to ovarian tumors. In preparation for a clinical trial to use MSC as MV carriers, we obtained cells from ovarian cancer patients and evaluated feasibility and safety of this approach. Methods MSC from adipose tissues of healthy donors (hMSC) and nine ovarian cancer patients (ovMSC) were characterized for susceptibility to virus infection and tumor homing abilities. Results Adipose tissue (range 0.16-3.96 grams) from newly diagnosed and recurrent ovarian cancer patients yielded about 7.41×106 cells at passage 1 (range 4–9 days). Phenotype and doubling times of MSC were similar between ovarian patients and healthy controls. The time to harvest of 3.0×108 cells (clinical dose) could be achieved by day 14 (range, 9–17 days). Two of nine samples tested had an abnormal karyotype represented by trisomy 20. Despite receiving up to 1.6×109 MSC/kg, no tumors were seen in SCID beige mice and MSC did not promote the growth of SKOV3 human ovarian cancer cells in mice. The ovMSC migrated towards primary ovarian cancer samples in chemotaxis assays and to ovarian tumors in athymic mice. Using non-invasive SPECT-CT imaging, we saw rapid co-localization, within 5–8 minutes of intraperitoneal administration of MV infected MSC to the ovarian tumors. Importantly, MSC can be pre-infected with MV, stored in liquid nitrogen and thawed on the day of infusion into mice without loss of activity. MV infected MSC, but not virus alone, significantly prolonged the survival of measles immune ovarian cancer bearing animals. Conclusions These studies confirmed the feasibility of using patient derived MSC as carriers for oncolytic MV therapy. We propose an approach where MSC from ovarian cancer patients will be expanded, frozen and validated to ensure compliance with the release criteria. On the treatment day, the cells will be thawed, washed, mixed with virus, briefly centrifuged and incubated for 2 hours with virus prior to infusion of the virus/MSC cocktail into patients. PMID:23347343
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Hwang, Dusun; Yoon, Dong-Jin; Kwon, Il-Bum; Seo, Dae-Cheol; Chung, Youngjoo
2010-05-10
A novel method for auto-correction of fiber optic distributed temperature sensor using anti-Stokes Raman back-scattering and its reflected signal is presented. This method processes two parts of measured signal. One part is the normal back scattered anti-Stokes signal and the other part is the reflected signal which eliminate not only the effect of local losses due to the micro-bending or damages on fiber but also the differential attenuation. Because the beams of the same wavelength are used to cancel out the local variance in transmission medium there is no differential attenuation inherently. The auto correction concept was verified by the bending experiment on different bending points. (c) 2010 Optical Society of America.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Kim, Kyungsang; Ye, Jong Chul, E-mail: jong.ye@kaist.ac.kr; Lee, Taewon
2015-09-15
Purpose: In digital breast tomosynthesis (DBT), scatter correction is highly desirable, as it improves image quality at low doses. Because the DBT detector panel is typically stationary during the source rotation, antiscatter grids are not generally compatible with DBT; thus, a software-based scatter correction is required. This work proposes a fully iterative scatter correction method that uses a novel fast Monte Carlo simulation (MCS) with a tissue-composition ratio estimation technique for DBT imaging. Methods: To apply MCS to scatter estimation, the material composition in each voxel should be known. To overcome the lack of prior accurate knowledge of tissue compositionmore » for DBT, a tissue-composition ratio is estimated based on the observation that the breast tissues are principally composed of adipose and glandular tissues. Using this approximation, the composition ratio can be estimated from the reconstructed attenuation coefficients, and the scatter distribution can then be estimated by MCS using the composition ratio. The scatter estimation and image reconstruction procedures can be performed iteratively until an acceptable accuracy is achieved. For practical use, (i) the authors have implemented a fast MCS using a graphics processing unit (GPU), (ii) the MCS is simplified to transport only x-rays in the energy range of 10–50 keV, modeling Rayleigh and Compton scattering and the photoelectric effect using the tissue-composition ratio of adipose and glandular tissues, and (iii) downsampling is used because the scatter distribution varies rather smoothly. Results: The authors have demonstrated that the proposed method can accurately estimate the scatter distribution, and that the contrast-to-noise ratio of the final reconstructed image is significantly improved. The authors validated the performance of the MCS by changing the tissue thickness, composition ratio, and x-ray energy. The authors confirmed that the tissue-composition ratio estimation was quite accurate under a variety of conditions. Our GPU-based fast MCS implementation took approximately 3 s to generate each angular projection for a 6 cm thick breast, which is believed to make this process acceptable for clinical applications. In addition, the clinical preferences of three radiologists were evaluated; the preference for the proposed method compared to the preference for the convolution-based method was statistically meaningful (p < 0.05, McNemar test). Conclusions: The proposed fully iterative scatter correction method and the GPU-based fast MCS using tissue-composition ratio estimation successfully improved the image quality within a reasonable computational time, which may potentially increase the clinical utility of DBT.« less
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2014-01-01
Background Mesenchymal stem cells (MSC) are multipotent progenitor cells characterized by their ability to both self-renew and differentiate into tissues of mesodermal origin. The plasticity or transdifferentiation potential of MSC is not limited to mesodermal derivatives, since under appropriate cell culture conditions and stimulation by bioactive factors, MSC have also been differentiated into endodermal (hepatocytes) and neuroectodermal (neurons) cells. The potential of MSC for hepatogenic and neurogenic differentiation has been well documented in different animal models; however, few reports are currently available on large animal models. In the present study we sought to characterize the hepatogenic and neurogenic differentiation and multipotent potential of bovine MSC (bMSC) isolated from bone marrow (BM) of abattoir-derived fetuses. Results Plastic-adherent bMSC isolated from fetal BM maintained a fibroblast-like morphology under monolayer culture conditions. Flow cytometric analysis demonstrated that bMSC populations were positive for MSC markers CD29 and CD73 and pluripotency markers OCT4 and NANOG; whereas, were negative for hematopoietic markers CD34 and CD45. Levels of mRNA of hepatic genes α-fetoprotein (AFP), albumin (ALB), alpha1 antitrypsin (α1AT), connexin 32 (CNX32), tyrosine aminotransferase (TAT) and cytochrome P450 (CYP3A4) were up-regulated in bMSC during a 28-Day period of hepatogenic differentiation. Functional analyses in differentiated bMSC cultures evidenced an increase (P < 0.05) in albumin and urea production and glycogen storage. bMSC cultured under neurogenic conditions expressed NESTIN and MAP2 proteins at 24 h of culture; whereas, at 144 h also expressed TRKA and PrPC. Levels of MAP2 and TRKA mRNA were up-regulated at the end of the differentiation period. Conversely, bMSC expressed lower levels of NANOG mRNA during both hepatogenic and neurogenic differentiation processes. Conclusion The expression patterns of linage-specific markers and the production of functional metabolites support the potential for hepatogenic and neurogenic differentiation of bMSC isolated from BM of abattoir-derived fetuses. The simplicity of isolation and the potential to differentiate into a wide variety of cell lineages lays the foundation for bMSC as an interesting alternative for investigation in MSC biology and eventual applications for regenerative therapy in veterinary medicine. PMID:25011474
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An empirical correction for moderate multiple scattering in super-heterodyne light scattering.
Botin, Denis; Mapa, Ludmila Marotta; Schweinfurth, Holger; Sieber, Bastian; Wittenberg, Christopher; Palberg, Thomas
2017-05-28
Frequency domain super-heterodyne laser light scattering is utilized in a low angle integral measurement configuration to determine flow and diffusion in charged sphere suspensions showing moderate to strong multiple scattering. We introduce an empirical correction to subtract the multiple scattering background and isolate the singly scattered light. We demonstrate the excellent feasibility of this simple approach for turbid suspensions of transmittance T ≥ 0.4. We study the particle concentration dependence of the electro-kinetic mobility in low salt aqueous suspension over an extended concentration regime and observe a maximum at intermediate concentrations. We further use our scheme for measurements of the self-diffusion coefficients in the fluid samples in the absence or presence of shear, as well as in polycrystalline samples during crystallization and coarsening. We discuss the scope and limits of our approach as well as possible future applications.
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Use of the Wigner representation in scattering problems
NASA Technical Reports Server (NTRS)
Bemler, E. A.
1975-01-01
The basic equations of quantum scattering were translated into the Wigner representation, putting quantum mechanics in the form of a stochastic process in phase space, with real valued probability distributions and source functions. The interpretative picture associated with this representation is developed and stressed and results used in applications published elsewhere are derived. The form of the integral equation for scattering as well as its multiple scattering expansion in this representation are derived. Quantum corrections to classical propagators are briefly discussed. The basic approximation used in the Monte-Carlo method is derived in a fashion which allows for future refinement and which includes bound state production. Finally, as a simple illustration of some of the formalism, scattering is treated by a bound two body problem. Simple expressions for single and double scattering contributions to total and differential cross-sections as well as for all necessary shadow corrections are obtained.
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Künzel, R; Herdade, S B; Costa, P R; Terini, R A; Levenhagen, R S
2006-04-21
In this study, scattered x-ray distributions were produced by irradiating a tissue equivalent phantom under clinical mammographic conditions by using Mo/Mo, Mo/Rh and W/Rh anode/filter combinations, for 25 and 30 kV tube voltages. Energy spectra of the scattered x-rays have been measured with a Cd(0.9)Zn(0.1)Te (CZT) detector for scattering angles between 30 degrees and 165 degrees . Measurement and correction processes have been evaluated through the comparison between the values of the half-value layer (HVL) and air kerma calculated from the corrected spectra and measured with an ionization chamber in a nonclinical x-ray system with a W/Mo anode/filter combination. The shape of the corrected x-ray spectra measured in the nonclinical system was also compared with those calculated using semi-empirical models published in the literature. Scattered x-ray spectra measured in the clinical x-ray system have been characterized through the calculation of HVL and mean photon energy. Values of the air kerma, ambient dose equivalent and effective dose have been evaluated through the corrected x-ray spectra. Mean conversion coefficients relating the air kerma to the ambient dose equivalent and to the effective dose from the scattered beams for Mo/Mo, Mo/Rh and W/Rh anode/filter combinations were also evaluated. Results show that for the scattered radiation beams the ambient dose equivalent provides an overestimate of the effective dose by a factor of about 5 in the mammography energy range. These results can be used in the control of the dose limits around a clinical unit and in the calculation of more realistic protective shielding barriers in mammography.
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Engineering mesenchymal stem cells for regenerative medicine and drug delivery.
Park, Ji Sun; Suryaprakash, Smruthi; Lao, Yeh-Hsing; Leong, Kam W
2015-08-01
Researchers have applied mesenchymal stem cells (MSC) to a variety of therapeutic scenarios by harnessing their multipotent, regenerative, and immunosuppressive properties with tropisms toward inflamed, hypoxic, and cancerous sites. Although MSC-based therapies have been shown to be safe and effective to a certain degree, the efficacy remains low in most cases when MSC are applied alone. To enhance their therapeutic efficacy, researchers have equipped MSC with targeted delivery functions using genetic engineering, therapeutic agent incorporation, and cell surface modification. MSC can be genetically modified virally or non-virally to overexpress therapeutic proteins that complement their innate properties. MSC can also be primed with non-peptidic drugs or magnetic nanoparticles for enhanced efficacy and externally regulated targeting, respectively. Furthermore, MSC can be functionalized with targeting moieties to augment their homing toward therapeutic sites using enzymatic modification, chemical conjugation, or non-covalent interactions. These engineering techniques are still works in progress, requiring optimization to improve the therapeutic efficacy and targeting effectiveness while minimizing any loss of MSC function. In this review, we will highlight the advanced techniques of engineering MSC, describe their promise and the challenges of translation into clinical settings, and suggest future perspectives on realizing their full potential for MSC-based therapy. Copyright © 2015 Elsevier Inc. All rights reserved.
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Theoretical interpretation of the Venus 1.05-micron CO2 band and the Venus 0.8189-micron H2O line.
NASA Technical Reports Server (NTRS)
Regas, J. L.; Giver, L. P.; Boese, R. W.; Miller, J. H.
1972-01-01
The synthetic-spectrum technique was used in the analysis. The synthetic spectra were constructed with a model which takes into account both isotropic scattering and the inhomogeneity in the Venus atmosphere. The Potter-Hansen correction factor was used to correct for anisotropic scattering. The synthetic spectra obtained are, therefore, the first which contain all the essential physics of line formation. The results confirm Potter's conclusion that the Venus cloud tops resemble terrestrial cirrus or stratus clouds in their scattering properties.
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NASA Astrophysics Data System (ADS)
Wang, Chao; Xiao, Jun; Luo, Xiaobing
2016-10-01
The neutron inelastic scattering cross section of 115In has been measured by the activation technique at neutron energies of 2.95, 3.94, and 5.24 MeV with the neutron capture cross sections of 197Au as an internal standard. The effects of multiple scattering and flux attenuation were corrected using the Monte Carlo code GEANT4. Based on the experimental values, the 115In neutron inelastic scattering cross sections data were theoretically calculated between the 1 and 15 MeV with the TALYS software code, the theoretical results of this study are in reasonable agreement with the available experimental results.
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Msc1 acts through histone H2A.Z to promote chromosome stability in Schizosaccharomyces pombe.
Ahmed, Shakil; Dul, Barbara; Qiu, Xinxing; Walworth, Nancy C
2007-11-01
As a central component of the DNA damage checkpoint pathway, the conserved protein kinase Chk1 mediates cell cycle progression when DNA damage is generated. Msc1 was identified as a multicopy suppressor capable of facilitating survival in response to DNA damage of cells mutant for chk1. We demonstrate that loss of msc1 function results in an increased rate of chromosome loss and that an msc1 null allele exhibits genetic interactions with mutants in key kinetochore components. Multicopy expression of msc1 robustly suppresses a temperature-sensitive mutant (cnp1-1) in the centromere-specific histone H3 variant CENP-A, and localization of CENP-A to the centromere is compromised in msc1 null cells. We present several lines of evidence to suggest that Msc1 carries out its function through the histone H2A variant H2A.Z, encoded by pht1 in fission yeast. Like an msc1 mutant, a pht1 mutant also exhibits chromosome instability and genetic interactions with kinetochore mutants. Suppression of cnp1-1 by multicopy msc1 requires pht1. Likewise, suppression of the DNA damage sensitivity of a chk1 mutant by multicopy msc1 also requires pht1. We present the first genetic evidence that histone H2A.Z may participate in centromere function in fission yeast and propose that Msc1 acts through H2A.Z to promote chromosome stability and cell survival following DNA damage.
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Msc1 Acts Through Histone H2A.Z to Promote Chromosome Stability in Schizosaccharomyces pombe
Ahmed, Shakil; Dul, Barbara; Qiu, Xinxing; Walworth, Nancy C.
2007-01-01
As a central component of the DNA damage checkpoint pathway, the conserved protein kinase Chk1 mediates cell cycle progression when DNA damage is generated. Msc1 was identified as a multicopy suppressor capable of facilitating survival in response to DNA damage of cells mutant for chk1. We demonstrate that loss of msc1 function results in an increased rate of chromosome loss and that an msc1 null allele exhibits genetic interactions with mutants in key kinetochore components. Multicopy expression of msc1 robustly suppresses a temperature-sensitive mutant (cnp1-1) in the centromere-specific histone H3 variant CENP-A, and localization of CENP-A to the centromere is compromised in msc1 null cells. We present several lines of evidence to suggest that Msc1 carries out its function through the histone H2A variant H2A.Z, encoded by pht1 in fission yeast. Like an msc1 mutant, a pht1 mutant also exhibits chromosome instability and genetic interactions with kinetochore mutants. Suppression of cnp1-1 by multicopy msc1 requires pht1. Likewise, suppression of the DNA damage sensitivity of a chk1 mutant by multicopy msc1 also requires pht1. We present the first genetic evidence that histone H2A.Z may participate in centromere function in fission yeast and propose that Msc1 acts through H2A.Z to promote chromosome stability and cell survival following DNA damage. PMID:17947424
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Sardesai, Varda S.; Shafiee, Abbas; Fisk, Nicholas M.
2017-01-01
Abstract Human placenta is rich in mesenchymal stem/stromal cells (MSC), with their origin widely presumed fetal. Cultured placental MSCs are confounded by a high frequency of maternal cell contamination. Our recent systematic review concluded that only a small minority of placental MSC publications report fetal/maternal origin, and failed to discern a specific methodology for isolation of fetal MSC from term villi. We determined isolation conditions to yield fetal and separately maternal MSC during ex vivo expansion from human term placenta. MSCs were isolated via a range of methods in combination; selection from various chorionic regions, different commercial media, mononuclear cell digest and/or explant culture. Fetal and maternal cell identities were quantitated in gender‐discordant pregnancies by XY chromosome fluorescence in situ hybridization. We first demonstrated reproducible maternal cell contamination in MSC cultures from all chorionic anatomical locations tested. Cultures in standard media rapidly became composed entirely of maternal cells despite isolation from fetal villi. To isolate pure fetal cells, we validated a novel isolation procedure comprising focal dissection from the cotyledonary core, collagenase/dispase digestion and explant culture in endothelial growth media that selected, and provided a proliferative environment, for fetal MSC. Comparison of MSC populations within the same placenta confirmed fetal to be smaller, more osteogenic and proliferative than maternal MSC. We conclude that in standard media, fetal chorionic villi‐derived MSC (CV‐MSC) do not grow readily, whereas maternal MSC proliferate to result in maternal overgrowth during culture. Instead, fetal CV‐MSCs require isolation under specific conditions, which has implications for clinical trials using placental MSC. Stem Cells Translational Medicine 2017;6:1070–1084 PMID:28205414
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Mesenchymal stem cells induce epithelial proliferation within the inflamed stomach.
Donnelly, Jessica M; Engevik, Amy; Feng, Rui; Xiao, Chang; Boivin, Gregory P; Li, Jing; Houghton, JeanMarie; Zavros, Yana
2014-06-15
Bone marrow-derived mesenchymal stem cells (MSCs) sustain cancer cells by creating a microenvironment favorable for tumor growth. In particular, MSCs have been implicated in gastric cancer development. There is extensive evidence suggesting that Hedgehog signaling regulates tumor growth. However, very little is known regarding the precise roles of Hedgehog signaling and MSCs in tumor development within the stomach. The current study tests that hypothesis that Sonic Hedgehog (Shh), secreted from MSCs, provides a proliferative stimulus for the gastric epithelium in the presence of inflammation. Red fluorescent protein-expressing MSCs transformed in vitro (stMSCs) were transduced with lentiviral constructs containing a vector control (stMSC(vect)) or short hairpin RNA (shRNA) targeting the Shh gene (stMSC(ShhKO)). Gastric submucosal transplantation of wild-type MSCs (wtMSCs), wild-type MSCs overexpressing Shh (wtMSC(Shh)), stMSC(vect), or stMSC(ShhKO) cells in C57BL/6 control (BL/6) or gastrin-deficient (GKO) mice was performed and mice analyzed 30 and 60 days posttransplantation. Compared with BL/6 mice transplanted with wtMSC(Shh) and stMSC(vect) cells, inflamed GKO mice developed aggressive gastric tumors. Tumor development was not observed in mouse stomachs transplanted with wtMSC or stMSC(ShhKO) cells. Compared with stMSC(ShhKO)-transplanted mice, within the inflamed GKO mouse stomach, Shh-expressing stMSC(vect)- and wtMSC(Shh)-induced proliferation of CD44-positive cells. CD44-positive cells clustered in gland-like structures within the tumor stroma and were positive for Patched (Ptch) expression. We conclude that Shh, secreted from MSCs, provides a proliferative stimulus for the gastric epithelium that is associated with tumor development, a response that is sustained by chronic inflammation. Copyright © 2014 the American Physiological Society.
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Zou, Xiangyu; Jiang, Kai; Puranik, Amrutesh S.; Jordan, Kyra L.; Tang, Hui
2018-01-01
Abstract Mesenchymal stem cells (MSC) have been experimentally used for kidney repair, but modest retention limits their efficacy. Cell‐surface coating allows modulating MSC homing and interaction with target cells. We coated mouse adipose tissue‐derived MSC with antibodies directed against kidney injury molecule‐1 (ab‐KIM1), which is upregulated in injured kidneys, and tested the hypothesis that this would enhance their therapeutic effects in ischemic kidney injury. Untreated MSC, ab‐KIM1‐coated MSC (KIM‐MSC), or vehicle, were injected systemically into the carotid artery of 2‐kidneys, 1‐clip mice 2 weeks after surgery. MSC retention in different organs was explored 24 hours, 48 hours, or 2 weeks after injection. Renal volume, perfusion, and oxygenation were studied 2 weeks after injection using magnetic resonance imaging in vivo, and renal inflammation, apoptosis, capillary density, and fibrosis ex vivo. The ab‐KIM1 coating had little effect on MSC viability or proliferation. The stenotic kidney showed upregulated KIM1 expression, selective homing, and greater retention of KIM‐MSC compared to untreated MSC and compared to other organs. KIM‐MSC‐injected mice improved renal perfusion and capillary density, and attenuated oxidative damage, apoptosis, and fibrosis compared to mice treated with vehicle or with native MSC. In conclusion, MSC coating with ab‐KIM1 increased their retention in the ischemic kidney and enhanced their therapeutic efficacy. This novel method may be useful to selectively target injured kidneys, and supports further development of strategies to enhance cell‐based treatment of ischemic kidney injury. Stem Cells Translational Medicine 2018;7:394–403 PMID:29446551
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Cappa, Christopher D.; Kolesar, Katheryn R.; Zhang, Xiaolu; ...
2016-05-27
Here, measurements of the optical properties (absorption, scattering and extinction) of PM 1, PM 2.5 and PM 10 made at two sites around Sacramento, CA, during the June 2010 Carbonaceous Aerosols and Radiative Effects Study (CARES) are reported. These observations are used to establish relationships between various intensive optical properties and to derive information about the dependence of the optical properties on photochemical aging and sources. Supermicron particles contributed substantially to the total light scattering at both sites, about 50 % on average. A strong, linear relationship is observed between the scattering Ångström exponent for PM 10 and the fraction of themore » scattering that is contributed by submicron particles ( f sca, PM 1 ) at both sites and with similar slopes and intercepts (for a given pair of wavelengths), suggesting that the derived relationship may be generally applicable for understanding variations in particle size distributions from remote sensing measurements. At the more urban T0 site, the f sca, PM 1 increased with photochemical age, whereas at the downwind, more rural T1 site the f sca, PM 1 decreased slightly with photochemical age. This difference in behavior reflects differences in transport, local production and local emission of supermicron particles between the sites. Light absorption is dominated by submicron particles, but there is some absorption by supermicron particles (~15 % of the total). The supermicron absorption derives from a combination of black carbon that has penetrated into the supermicron mode and from dust, and there is a clear increase in the mass absorption coefficient of just the supermicron particles with increasing average particle size. The mass scattering coefficient (MSC) for the supermicron particles was directly observed to vary inversely with the average particle size, demonstrating that MSC cannot always be treated as a constant in estimating mass concentrations from scattering measurements, or vice versa. The total particle backscatter fraction exhibited some dependence upon the relative abundance of sub- versus supermicron particles; however this was modulated by variations in the median size of particles within a given size range; variations in the submicron size distribution had a particularly large influence on the observed backscatter efficiency and an approximate method to account for this variability is introduced. The relationship between the absorption and scattering Ångström exponents is examined and used to update a previously suggested particle classification scheme. Differences in composition led to differences in the sensitivity of PM 2.5 to heating in a thermodenuder to the average particle size, with more extensive evaporation (observed as a larger decrease in the PM 2.5 extinction coefficient) corresponding to smaller particles; i.e., submicron particles were generally more susceptible to heating than the supermicron particles. The influence of heating on the particle hygroscopicity varied with the effective particle size, with larger changes observed when the PM 2.5 distribution was dominated by smaller particles.« less
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Cappa, Christopher D.; Kolesar, Katheryn R.; Zhang, Xiaolu
Here, measurements of the optical properties (absorption, scattering and extinction) of PM 1, PM 2.5 and PM 10 made at two sites around Sacramento, CA, during the June 2010 Carbonaceous Aerosols and Radiative Effects Study (CARES) are reported. These observations are used to establish relationships between various intensive optical properties and to derive information about the dependence of the optical properties on photochemical aging and sources. Supermicron particles contributed substantially to the total light scattering at both sites, about 50 % on average. A strong, linear relationship is observed between the scattering Ångström exponent for PM 10 and the fraction of themore » scattering that is contributed by submicron particles ( f sca, PM 1 ) at both sites and with similar slopes and intercepts (for a given pair of wavelengths), suggesting that the derived relationship may be generally applicable for understanding variations in particle size distributions from remote sensing measurements. At the more urban T0 site, the f sca, PM 1 increased with photochemical age, whereas at the downwind, more rural T1 site the f sca, PM 1 decreased slightly with photochemical age. This difference in behavior reflects differences in transport, local production and local emission of supermicron particles between the sites. Light absorption is dominated by submicron particles, but there is some absorption by supermicron particles (~15 % of the total). The supermicron absorption derives from a combination of black carbon that has penetrated into the supermicron mode and from dust, and there is a clear increase in the mass absorption coefficient of just the supermicron particles with increasing average particle size. The mass scattering coefficient (MSC) for the supermicron particles was directly observed to vary inversely with the average particle size, demonstrating that MSC cannot always be treated as a constant in estimating mass concentrations from scattering measurements, or vice versa. The total particle backscatter fraction exhibited some dependence upon the relative abundance of sub- versus supermicron particles; however this was modulated by variations in the median size of particles within a given size range; variations in the submicron size distribution had a particularly large influence on the observed backscatter efficiency and an approximate method to account for this variability is introduced. The relationship between the absorption and scattering Ångström exponents is examined and used to update a previously suggested particle classification scheme. Differences in composition led to differences in the sensitivity of PM 2.5 to heating in a thermodenuder to the average particle size, with more extensive evaporation (observed as a larger decrease in the PM 2.5 extinction coefficient) corresponding to smaller particles; i.e., submicron particles were generally more susceptible to heating than the supermicron particles. The influence of heating on the particle hygroscopicity varied with the effective particle size, with larger changes observed when the PM 2.5 distribution was dominated by smaller particles.« less
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NASA Astrophysics Data System (ADS)
Cappa, Christopher D.; Kolesar, Katheryn R.; Zhang, Xiaolu; Atkinson, Dean B.; Pekour, Mikhail S.; Zaveri, Rahul A.; Zelenyuk, Alla; Zhang, Qi
2016-05-01
Measurements of the optical properties (absorption, scattering and extinction) of PM1, PM2.5 and PM10 made at two sites around Sacramento, CA, during the June 2010 Carbonaceous Aerosols and Radiative Effects Study (CARES) are reported. These observations are used to establish relationships between various intensive optical properties and to derive information about the dependence of the optical properties on photochemical aging and sources. Supermicron particles contributed substantially to the total light scattering at both sites, about 50 % on average. A strong, linear relationship is observed between the scattering Ångström exponent for PM10 and the fraction of the scattering that is contributed by submicron particles (fsca, PM
1 ) at both sites and with similar slopes and intercepts (for a given pair of wavelengths), suggesting that the derived relationship may be generally applicable for understanding variations in particle size distributions from remote sensing measurements. At the more urban T0 site, the fsca, PM1 increased with photochemical age, whereas at the downwind, more rural T1 site the fsca, PM1 decreased slightly with photochemical age. This difference in behavior reflects differences in transport, local production and local emission of supermicron particles between the sites. Light absorption is dominated by submicron particles, but there is some absorption by supermicron particles ( ˜ 15 % of the total). The supermicron absorption derives from a combination of black carbon that has penetrated into the supermicron mode and from dust, and there is a clear increase in the mass absorption coefficient of just the supermicron particles with increasing average particle size. The mass scattering coefficient (MSC) for the supermicron particles was directly observed to vary inversely with the average particle size, demonstrating that MSC cannot always be treated as a constant in estimating mass concentrations from scattering measurements, or vice versa. The total particle backscatter fraction exhibited some dependence upon the relative abundance of sub- versus supermicron particles; however this was modulated by variations in the median size of particles within a given size range; variations in the submicron size distribution had a particularly large influence on the observed backscatter efficiency and an approximate method to account for this variability is introduced. The relationship between the absorption and scattering Ångström exponents is examined and used to update a previously suggested particle classification scheme. Differences in composition led to differences in the sensitivity of PM2.5 to heating in a thermodenuder to the average particle size, with more extensive evaporation (observed as a larger decrease in the PM2.5 extinction coefficient) corresponding to smaller particles; i.e., submicron particles were generally more susceptible to heating than the supermicron particles. The influence of heating on the particle hygroscopicity varied with the effective particle size, with larger changes observed when the PM2.5 distribution was dominated by smaller particles. -
Wang, Shuai; Li, Yi; Zhao, Jinghong; Zhang, Jingbo; Huang, Yunjian
2013-04-01
Mesenchymal stem cells (MSC) attenuate albuminuria and preserve normal renal histology in diabetic mice. However, the effects of MSC on glomerular podocyte injury remain uncertain. The aim of this study was to evaluate the effects of MSC on podocyte injury in streptozotocin (STZ)-induced diabetic rats. Thirty days after diabetes induction by STZ injection (65 mg/kg, intraperitoneally) in Sprague-Dawley rats, the diabetic rats received medium or 2 × 10(6) enhanced green fluorescent protein-labeled MSC via the renal artery. In vivo tracking of MSC was followed by immunofluorescence analysis. Diabetes-related physical and biochemical parameters were measured on day 60 after the MSC infusion. The expression of podocyte markers (nephrin and podocin), podocyte survival factors (VEGF and BMP-7), and the ultrastructural pathology of podocytes were also assessed. MSC were only detected in the glomeruli from the left kidney receiving MSC infusion. Compared with medium-treated diabetic rats, rats treated with MSC showed a suppressed increase in kidney weight, kidney to body weight index, creatinine clearance rate, and urinary albumin to creatinine ratio; however, the treatment had no effect on blood glucose or body weight levels. Furthermore, the MSC treatment reduced the loss of podocytes, effacement of foot processes, widening of foot processes, thickening of glomerular basal membrane (GBM), and loss of glomerular nephrin and podocin. Most important, MSC-injected kidneys expressed higher levels of BMP-7 but not of VEGF. Our results clearly demonstrated that intra-arterial administration of MSC prevented the development of albuminuria as well as any damage to or loss of podocytes, though there was no improvement in blood sugar levels. The protective effects of MSC may be mediated in part by increasing BMP-7 secretion. Copyright © 2013 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.
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Sangiorgi, Bruno; De Freitas, Helder Teixeira; Schiavinato, Josiane Lilian Dos Santos; Leão, Vitor; Haddad, Rodrigo; Orellana, Maristela Delgado; Faça, Vitor Marcel; Ferreira, Germano Aguiar; Covas, Dimas Tadeu; Zago, Marco Antônio; Panepucci, Rodrigo Alexandre
2016-07-01
Multipotent mesenchymal stromal cells (MSC) are imbued with an immunosuppressive phenotype that extends to several immune system cells. In this study, we evaluated how distinct Toll-like receptor (TLR) agonists impact immunosuppressive properties of bone marrow (BM)-MSC and explored the potential mechanisms involved. We show that TLR4 stimulation by lipopolysaccharide (LPS) restricted the ability of MSC to suppress the proliferation of T lymphocytes, increasing the gene expression of interleukin (IL)-1β and IL-6. In contrast, stimulation of TLR9 by DSP30 induced proliferation and the suppressive potential of BM-MSC, coinciding with reducing tumor necrosis factor (TNF)-α expression, increased expression of transforming growth factor (TGF)-β1, increased percentages of BM-MSC double positive for the ectonucleotidases CD39+CD73+ and adenosine levels. Importantly, following simultaneous stimulation with LPS and DSP30, BM-MSC's ability to suppress T lymphocyte proliferation was comparable with that of non-stimulated BM-MSC levels. Moreover, stimulation of BM-MSC with LPS reduced significantly the gene expression levels, on co-cultured T lymphocyte, of IL-10 and interferon (IFN)γ, a cytokine with potential to enhance the immunosuppression mediated by MSC and ameliorate the clinical outcome of patients with graft-versus-host disease (GVHD). Altogether, our findings reiterate the harmful effects of LPS on MSC immunosuppression, besides indicating that DSP30 could provide a protective effect against LPS circulating in the blood of GVHD patients who receive BM-MSC infusions, ensuring a more predictable immunosuppressive effect. The novel effects and potential mechanisms following the stimulation of BM-MSC by DSP30 might impact their clinical use, by allowing the derivation of optimal "licensing" protocols for obtaining therapeutically efficient MSC. Copyright © 2016 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.
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[Experimental study on dog's bone marrow stem cells transfected by pIRES2-EGFP-IGF-1 gene].
Zhu, Guo-qiang; Wu, Zhi-fen; Li, Yuan-fei; Hu, De-hua; Wang, Qin-tao
2006-12-01
To establish the bone marrow stem cells (MSC) model which could highly express the insulin-like growth factor 1 (IGF-1) transfected by dog's IGF-1 gene. pIRES2-EGFP-IGF-1 was transfected into MSC by lipofectamine. Positive clones were selected with G418. The expression of IGF-1 protein in the MSC was determined by immunohistochemistry and Western blot analysis. The IGF-1 in the supernatant of the transfected MSC was detected by sandwich-in ELISA. The periodontal ligament cells (PDLC) were cultured in the supernatant of the transfected MSC. The changes of PDLC' proliferation were observed by MTT. IGF-1-transfected MSC could apparently express IGF-1. The IGF-1 protein in the supernatant of the transfected MSC was confirmed by sandwich-in ELISA. IGF-1 could promote the PDLC' proliferation. The MSC transfected by dog's IGF-1 gene can highly express IGF-1, which may lay the foundation for further study on periodontal regeneration.
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[Construction of fetal mesenchymal stem cell cDNA subtractive library].
Yang, Li; Wang, Dong-Mei; Li, Liang; Bai, Ci-Xian; Cao, Hua; Li, Ting-Yu; Pei, Xue-Tao
2002-04-01
To identify differentially expressed genes between fetal mesenchymal stem cell (MSC) and adult MSC, especially specified genes expressed in fetal MSC, a cDNA subtractive library of fetal MSC was constructed using suppression subtractive hybridization (SSH) technique. At first, total RNA was isolated from fetal and adult MSC. Using SMART PCR synthesis method, single-strand and double-strand cDNAs were synthesized. After Rsa I digestion, fetal MSC cDNAs were divided into two groups and ligated to adaptor 1 and adaptor 2 respectively. Results showed that the amplified library contains 890 clones. Analysis of 890 clones with PCR demonstrated that 768 clones were positive. The positive rate is 86.3%. The size of inserted fragments in these positive clones was between 0.2 - 1 kb, with an average of 400 - 600 bp. SSH is a convenient and effective method for screening differentially expressed genes. The constructed cDNA subtractive library of fetal MSC cDNA lays solid foundation for screening and cloning new and specific function related genes of fetal MSC.
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Schönbichler, S A; Bittner, L K H; Weiss, A K H; Griesser, U J; Pallua, J D; Huck, C W
2013-08-01
The aim of this study was to evaluate the ability of near-infrared chemical imaging (NIR-CI), near-infrared (NIR), Raman and attenuated-total-reflectance infrared (ATR-IR) spectroscopy to quantify three polymorphic forms (I, II, III) of furosemide in ternary powder mixtures. For this purpose, partial least-squares (PLS) regression models were developed, and different data preprocessing algorithms such as normalization, standard normal variate (SNV), multiplicative scatter correction (MSC) and 1st to 3rd derivatives were applied to reduce the influence of systematic disturbances. The performance of the methods was evaluated by comparison of the standard error of cross-validation (SECV), R(2), and the ratio performance deviation (RPD). Limits of detection (LOD) and limits of quantification (LOQ) of all methods were determined. For NIR-CI, a SECVcorr-spec and a SECVsingle-pixel corrected were calculated to assess the loss of accuracy by taking advantage of the spatial information. NIR-CI showed a SECVcorr-spec (SECVsingle-pixel corrected) of 2.82% (3.71%), 3.49% (4.65%), and 4.10% (5.06%) for form I, II, III. NIR had a SECV of 2.98%, 3.62%, and 2.75%, and Raman reached 3.25%, 3.08%, and 3.18%. The SECV of the ATR-IR models were 7.46%, 7.18%, and 12.08%. This study proves that NIR-CI, NIR, and Raman are well suited to quantify forms I-III of furosemide in ternary mixtures. Because of the pressure-dependent conversion of form II to form I, ATR-IR was found to be less appropriate for an accurate quantification of the mixtures. In this study, the capability of NIR-CI for the quantification of polymorphic ternary mixtures was compared with conventional spectroscopic techniques for the first time. For this purpose, a new way of spectra selection was chosen, and two kinds of SECVs were calculated to achieve a better comparability of NIR-CI to NIR, Raman, and ATR-IR. Copyright © 2013 Elsevier B.V. All rights reserved.
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Spectral peculiarities of electromagnetic wave scattering by Veselago's cylinders
NASA Astrophysics Data System (ADS)
Sukhov, S. V.; Shevyakhov, N. S.
2006-03-01
The results are presented of spectral calculations of extinction cross-section for scattering of E- and H-polarized electromagnetic waves by cylinders made of Veselago material. The insolvency of previously developed models of scattering is demonstrated. It is shown that correct description of scattering requires separate consideration of both electric and magnetic subsystems.
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Spectral peculiarities of electromagnetic wave scattered by Veselago's cylinders
NASA Astrophysics Data System (ADS)
Sukhov, S. V.; Shevyakhov, N. S.
2005-09-01
The results are presented of spectral calculations of extinction cross-section for scattering of E- and H-polarized electromagnetic waves by cylinders made of Veselago material. The insolvency of previously developed models of scattering is demonstrated. It is shown that correct description of scattering requires separate consideration of both electric and magnetic subsystems.
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Auto-transplanted mesenchymal stromal cell fate in periodontal tissue of beagle dogs.
Wei, Na; Gong, Ping; Liao, Dapeng; Yang, Xingmei; Li, Xiaoyu; Liu, Yurong; Yuan, Quan; Tan, Zhen
2010-07-01
Mesenchymal stromal cells (MSC) possess multilineage differentiation potential and characteristics of self-renewal. It has been reported that MSC can acquire characteristics of cells in the periodontal ligament (PDL) in vitro. Moreover, the transplantation of MSC has been shown to be a promising strategy for treating periodontal defects. However, little is known about the fate of MSC in periodontal tissue in vivo. The aim of this study was to trace the paths of MSC after transplantation into periodontal tissues in vivo. MSC labeled with bromodeoxyuridine (BrdU) were transplanted into periodontal defects of beagle dogs. Six weeks after surgery, the animals were killed and decalcified specimens were prepared. Migration and differentiation of MSC were detected by single/double immunohistochemistry and a combination of immunohistochemistry and in situ hybridization. BrdU-labeled MSC were observed distributing into periodontal tissue that included alveolar bone, PDL, cementum and blood vessels and expressing surface markers typical of osteoblasts and fibroblasts. Cumulatively, our data suggest that MSC migrate throughout periodontal tissue and differentiate into osteoblasts and fibroblasts after transplantation into periodontal defects at 6 weeks in vivo, and have the potential to regenerate periodontal tissue.
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Cahill, Emer F.; Kennelly, Helen; Carty, Fiona; Mahon, Bernard P.
2016-01-01
The incidence of idiopathic pulmonary fibrosis is on the rise and existing treatments have failed to halt or reverse disease progression. Mesenchymal stromal cells (MSCs) have potent cytoprotective effects, can promote tissue repair, and have demonstrated efficacy in a range of fibrotic lung diseases; however, the exact mechanisms of action remain to be elucidated. Chemical antagonists and short hairpin RNA knockdown were used to identify the mechanisms of action used by MSCs in promoting wound healing, proliferation, and inhibiting apoptosis. Using the bleomycin induced fibrosis model, the protective effects of early or late MSC administration were examined. The role for hepatocyte growth factor (HGF) in MSC protection against bleomycin lung injury was examined using HGF knockdown MSC. Terminal deoxynucleotidyl transferase (TdT) dUTP nick-end labeling assay was performed on ex vivo lung sections to examine the effects of MSC on apoptosis. MSC conditioned media (CM) enhanced wound closure and inhibited apoptosis of pulmonary cells in vitro. HGF was required for MSC CM enhancement of epithelial cell proliferation and inhibition of apoptosis. In contrast, MSC required COX-2 for CM to inhibit fibroblast proliferation. In a murine model, early administration of MSC protected against bleomycin induced lung fibrosis and correlated with reduced levels of the proinflammatory cytokine interleukin-1β, reduced levels of apoptosis, and significantly increased levels of HGF. These protective effects were in part mediated by MSC derived HGF as HGF knockdown MSC were unable to protect against fibrosis in vivo. These findings delineate the mechanisms of MSC protection in a preclinical model of fibrotic lung disease. Significance The mechanisms used by mesenchymal stromal cells (MSCs) in mediating protective effects in chronic models of lung disease are not understood and remain to be elucidated. These findings from in vitro studies highlight an important role for the MSC-derived soluble factors hepatocyte growth factor (HGF) and prostaglandin E2 in promoting wound healing and inhibiting apoptosis. Furthermore, this study translates these findings demonstrating an important role for HGF in the protective effects mediated by MSC in vivo in the bleomycin model. These findings support a targeted approach to enhancing MSC therapy for fibrotic disease and highlight the importance of timing of MSC therapy. PMID:27388243
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Fortmann, Carsten; Wierling, August; Röpke, Gerd
2010-02-01
The dynamic structure factor, which determines the Thomson scattering spectrum, is calculated via an extended Mermin approach. It incorporates the dynamical collision frequency as well as the local-field correction factor. This allows to study systematically the impact of electron-ion collisions as well as electron-electron correlations due to degeneracy and short-range interaction on the characteristics of the Thomson scattering signal. As such, the plasmon dispersion and damping width is calculated for a two-component plasma, where the electron subsystem is completely degenerate. Strong deviations of the plasmon resonance position due to the electron-electron correlations are observed at increasing Brueckner parameters r(s). These results are of paramount importance for the interpretation of collective Thomson scattering spectra, as the determination of the free electron density from the plasmon resonance position requires a precise theory of the plasmon dispersion. Implications due to different approximations for the electron-electron correlation, i.e., different forms of the one-component local-field correction, are discussed.
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Biophotonics of skin: method for correction of deep Raman spectra distorted by elastic scattering
NASA Astrophysics Data System (ADS)
Roig, Blandine; Koenig, Anne; Perraut, François; Piot, Olivier; Gobinet, Cyril; Manfait, Michel; Dinten, Jean-Marc
2015-03-01
Confocal Raman microspectroscopy allows in-depth molecular and conformational characterization of biological tissues non-invasively. Unfortunately, spectral distortions occur due to elastic scattering. Our objective is to correct the attenuation of in-depth Raman peaks intensity by considering this phenomenon, enabling thus quantitative diagnosis. In this purpose, we developed PDMS phantoms mimicking skin optical properties used as tools for instrument calibration and data processing method validation. An optical system based on a fibers bundle has been previously developed for in vivo skin characterization with Diffuse Reflectance Spectroscopy (DRS). Used on our phantoms, this technique allows checking their optical properties: the targeted ones were retrieved. Raman microspectroscopy was performed using a commercial confocal microscope. Depth profiles were constructed from integrated intensity of some specific PDMS Raman vibrations. Acquired on monolayer phantoms, they display a decline which is increasing with the scattering coefficient. Furthermore, when acquiring Raman spectra on multilayered phantoms, the signal attenuation through each single layer is directly dependent on its own scattering property. Therefore, determining the optical properties of any biological sample, obtained with DRS for example, is crucial to correct properly Raman depth profiles. A model, inspired from S.L. Jacques's expression for Confocal Reflectance Microscopy and modified at some points, is proposed and tested to fit the depth profiles obtained on the phantoms as function of the reduced scattering coefficient. Consequently, once the optical properties of a biological sample are known, the intensity of deep Raman spectra distorted by elastic scattering can be corrected with our reliable model, permitting thus to consider quantitative studies for purposes of characterization or diagnosis.
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Atmospheric scattering corrections to solar radiometry
NASA Technical Reports Server (NTRS)
Box, M. A.; Deepak, A.
1979-01-01
Whenever a solar radiometer is used to measure direct solar radiation, some diffuse sky radiation invariably enters the detector's field of view along with the direct beam. Therefore, the atmospheric optical depth obtained by the use of Bouguer's transmission law (also called Beer-Lambert's law), that is valid only for direct radiation, needs to be corrected by taking account of the scattered radiation. This paper discusses the correction factors needed to account for the diffuse (i,e., singly and multiply scattered) radiation and the algorithms developed for retrieving aerosol size distribution from such measurements. For a radiometer with a small field of view (half-cone angle of less than 5 deg) and relatively clear skies (optical depths less than 0.4), it is shown that the total diffuse contribution represents approximately 1% of the total intensity.
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In-Situ Bioreduction and Removal of Ammonium Perchlorate
2006-05-09
Ader, PhD. Max Coleman, PhD. Swades Chaudhuri, PhD. Susan O’Connor MSc, MSc Royce Bruce, MSc. Urania Michaelidou, MSc. Melissa Rice, MSc. Sarah...1993. SeqApp, 1.9a157 ed. Biocomputing Office, Biology Dept., Indiana University, Bloomington, IN. 44. Giordano , G., L. Saracino, and L. Grillet. 1985...Mutant of E. coli K-12. Biocimica et Biophysica Acta 839:181-190. 45. Guigliarelli, B., A. Magalon, M. Asso, P. Bertrand, C. Frixon, G. Giordano
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Civini, Sara; Pacelli, Consiglia; Dieng, Mame Massar; Lemieux, William; Jin, Ping; Bazin, Renée; Patey, Natacha; Marincola, Francesco M.; Moldovan, Florina; Zaouter, Charlotte; Trudeau, Louis-Eric; Benabdhalla, Basma; Louis, Isabelle; Beauséjour, Christian; Stroncek, David; Le Deist, Françoise; Haddad, Elie
2016-01-01
Human mesenchymal stromal cells (MSC) have been shown to dampen immune response and promote tissue repair, but the underlying mechanisms are still under investigation. Herein, we demonstrate that umbilical cord-derived MSC (UC-MSC) alter the phenotype and function of monocyte-derived dendritic cells (DC) through lactate-mediated metabolic reprogramming. UC-MSC can secrete large quantities of lactate and, when present during monocyte-to-DC differentiation, induce instead the acquisition of M2-macrophage features in terms of morphology, surface markers, migratory properties and antigen presentation capacity. Microarray expression profiling indicates that UC-MSC modify the expression of metabolic-related genes and induce a M2-macrophage expression signature. Importantly, monocyte-derived DC obtained in presence of UC-MSC, polarize naïve allogeneic CD4+ T-cells into Th2 cells. Treatment of UC-MSC with an inhibitor of lactate dehydrogenase strongly decreases lactate concentration in culture supernatant and abrogates the effect on monocyte-to-DC differentiation. Metabolic analysis further revealed that UC-MSC decrease oxidative phosphorylation in differentiating monocytes while strongly increasing the spare respiratory capacity proportional to the amount of secreted lactate. Because both MSC and monocytes are recruited in vivo at the site of tissue damage and inflammation, we propose the local increase of lactate concentration induced by UC-MSC and the consequent enrichment in M2-macrophage generation as a mechanism to achieve immunomodulation. PMID:27070086
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Chow, Lyndah; Johnson, Valerie; Regan, Dan; Wheat, William; Webb, Saiphone; Koch, Peter; Dow, Steven
2017-12-01
Mesenchymal stem cells (MSCs) exhibit broad immune modulatory activity in vivo and can suppress T cell proliferation and dendritic cell activation in vitro. Currently, most MSC for clinical usage are derived from younger donors, due to ease of procurement and to the superior immune modulatory activity. However, the use of MSC from multiple unrelated donors makes it difficult to standardize study results and compare outcomes between different clinical trials. One solution is the use of MSC derived from induced pluripotent stem cells (iPSC); as iPSC-derived MSC have nearly unlimited proliferative potential and exhibit in vitro phenotypic stability. Given the value of dogs as a spontaneous disease model for pre-clinical evaluation of stem cell therapeutics, we investigated the functional properties of canine iPSC-derived MSC (iMSC), including immune modulatory properties and potential for teratoma formation. We found that canine iMSC downregulated expression of pluripotency genes and appeared morphologically similar to conventional MSC. Importantly, iMSC retained a stable phenotype after multiple passages, did not form teratomas in immune deficient mice, and did not induce tumor formation in dogs following systemic injection. We concluded therefore that iMSC were phenotypically stable, immunologically potent, safe with respect to tumor formation, and represented an important new source of cells for therapeutic modulation of inflammatory disorders. Copyright © 2017. Published by Elsevier B.V.
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Wang, Zhifa; Weng, Yanming; Lu, Shengjun; Zong, Chunlin; Qiu, Jianyong; Liu, Yanpu; Liu, Bin
2015-08-01
To analyze the effects of platelet-rich fibrin (PRF) on mesenchymal stem cells (MSCs) in vitro and investigate in vivo bone formation by MSC sheets with PRF. Cell proliferation and expression of osteogenesis-related genes within MSC sheets were assessed upon exposure to PRF from the same donors. We then injected MSC sheet fragments with or without PRF subcutaneously in nude mice and assessed bone formation by micro-computed tomography and histological analyses. PRF significantly stimulated MSC proliferation and osteogenesis in vitro. MSC sheets injected with or without PRF formed new bone, but those with PRF produced significantly more and denser bone. MSC sheets can be used to generate tissue engineered bone upon injection, and PRF increases the osteogenic capacity of MSC sheets in vitro and in vivo. © 2014 Wiley Periodicals, Inc.
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A library least-squares approach for scatter correction in gamma-ray tomography
NASA Astrophysics Data System (ADS)
Meric, Ilker; Anton Johansen, Geir; Valgueiro Malta Moreira, Icaro
2015-03-01
Scattered radiation is known to lead to distortion in reconstructed images in Computed Tomography (CT). The effects of scattered radiation are especially more pronounced in non-scanning, multiple source systems which are preferred for flow imaging where the instantaneous density distribution of the flow components is of interest. In this work, a new method based on a library least-squares (LLS) approach is proposed as a means of estimating the scatter contribution and correcting for this. The validity of the proposed method is tested using the 85-channel industrial gamma-ray tomograph previously developed at the University of Bergen (UoB). The results presented here confirm that the LLS approach can effectively estimate the amounts of transmission and scatter components in any given detector in the UoB gamma-ray tomography system.
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NASA Astrophysics Data System (ADS)
Itoh, Naoki; Kawana, Youhei; Nozawa, Satoshi; Kohyama, Yasuharu
2001-10-01
We extend the formalism for the calculation of the relativistic corrections to the Sunyaev-Zel'dovich effect for clusters of galaxies and include the multiple scattering effects in the isotropic approximation. We present the results of the calculations by the Fokker-Planck expansion method as well as by the direct numerical integration of the collision term of the Boltzmann equation. The multiple scattering contribution is found to be very small compared with the single scattering contribution. For high-temperature galaxy clusters of kBTe~15keV, the ratio of both the contributions is -0.2 per cent in the Wien region. In the Rayleigh-Jeans region the ratio is -0.03 per cent. Therefore the multiple scattering contribution is safely neglected for the observed galaxy clusters.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Herzmann, Nicole; Salamon, Achim; Fiedler, Tomas
Multipotent mesenchymal stromal cells (MSC) are capable of multi-lineage differentiation and support regenerative processes. In bacterial infections, resident MSC can come intocontact with and need to react to bacterial components. Lipopolysaccharide (LPS), a typical structure of Gram-negative bacteria, increases the proliferation and osteogenic differentiation of MSC. LPS is usually recognized by the toll-like receptor (TLR) 4 and induces pro-inflammatory reactions in numerous cell types. In this study, we quantified the protein expression of TLR4 and CD14 on adipose-derived MSC (adMSC) in osteogenic differentiation and investigated the effect of TLR4 activation by LPS on NF-κB activation, proliferation and osteogenic differentiation ofmore » adMSC. We found that TLR4 is expressed on adMSC whereas CD14 is not, and that osteogenic differentiation induced an increase of the amount of TLR4 protein whereas LPS stimulation did not. Moreover, we could show that NF-κB activation via TLR4 occurs upon LPS treatment. Furthermore, we were able to show that competitive inhibition of TLR4 completely abolished the stimulatory effect of LPS on the proliferation and osteogenic differentiation of adMSC. In addition, the inhibition of TLR4 leads to the complete absence of osteogenic differentiation of adMSC, even when osteogenically stimulated. Thus, we conclude that LPS induces proliferation and osteogenic differentiation of adMSC in vitro through the activation of TLR4 and that the TLR4 receptor seems to play a role during osteogenic differentiation of adMSC.« less
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Mrugala, D; Bony, C; Neves, N; Caillot, L; Fabre, S; Moukoko, D; Jorgensen, C; Noël, D
2008-03-01
Multipotent mesenchymal stromal cells (MSC) are of particular interest for their potential clinical use in cartilage engineering, but a consistent model is missing in large animals. In the absence of any detailed study reporting a complete characterisation of the mesenchymal cells isolated from sheep bone marrow, we fully characterised adherent stromal cells and developed a pre-clinical model of cartilage engineering by implantation of autologous MSC in the Merinos sheep. Ovine MSC (oMSC) were isolated from bone marrow, expanded and further characterised according to the recently proposed definition of the MSC. The experimental model consists of partial-thickness lesions created in the inner part of the patellae of the posterior legs. Lesions were filled with oMSC with or without chitosan, with or without transforming growth factor (TGF)beta-3, in a fibrin clot. oMSC were shown to display the three main characteristics of MSC: adherence to plastic, phenotypic profile (positive for CD44, CD105, vimentin and negative for CD34 and CD45), and trilineage differentiation potential. We also report two other important functional characteristics of MSC: support of long-term haematopoiesis and immunosuppressive capacity. In vivo, 2 months after implantation the histological analysis revealed chondrocyte-like cells surrounded by a hyaline-like cartilaginous matrix that was integrated to the host cartilage when oMSC were combined with chitosan and TGFbeta-3. This study provides for the first time a strong characterisation of oMSC and establishes the basis for a model of cartilage engineering in a large animal.
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78 FR 29387 - Government-Owned Inventions, Available for Licensing
Federal Register 2010, 2011, 2012, 2013, 2014
2013-05-20
....: MSC-24919-1: Systems and Methods for RFID-Enables Information Collection; NASA Case No.: MSC-25632-1... Methods for RFID-Enabled Dispenser; NASA Case No.: MSC-25313-1: Hydrostatic Hyperbaric Apparatus and...; NASA Case No: MSC-25590-1: Systems and Methods for RFID-Enabled Pressure Sensing Apparatus; NASA Case...
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Reliability Analysis of the MSC System
NASA Astrophysics Data System (ADS)
Kim, Young-Soo; Lee, Do-Kyoung; Lee, Chang-Ho; Woo, Sun-Hee
2003-09-01
MSC (Multi-Spectral Camera) is the payload of KOMPSAT-2, which is being developed for earth imaging in optical and near-infrared region. The design of the MSC is completed and its reliability has been assessed from part level to the MSC system level. The reliability was analyzed in worst case and the analysis results showed that the value complies the required value of 0.9. In this paper, a calculation method of reliability for the MSC system is described, and assessment result is presented and discussed.
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NASA Astrophysics Data System (ADS)
Phillips, C. B.; Valenti, M.
2009-12-01
Jupiter's moon Europa likely possesses an ocean of liquid water beneath its icy surface, but estimates of the thickness of the surface ice shell vary from a few kilometers to tens of kilometers. Color images of Europa reveal the existence of a reddish, non-ice component associated with a variety of geological features. The composition and origin of this material is uncertain, as is its relationship to Europa's various landforms. Published analyses of Galileo Near Infrared Mapping Spectrometer (NIMS) observations indicate the presence of highly hydrated sulfate compounds. This non-ice material may also bear biosignatures or other signs of biotic material. Additional spectral information from the Galileo Solid State Imager (SSI) could further elucidate the nature of the surface deposits, particularly when combined with information from the NIMS. However, little effort has been focused on this approach because proper calibration of the color image data is challenging, requiring both skill and patience to process the data and incorporate the appropriate scattered light correction. We are currently working to properly calibrate the color SSI data. The most important and most difficult issue to address in the analysis of multispectral SSI data entails using thorough calibrations and a correction for scattered light. Early in the Galileo mission, studies of the Galileo SSI data for the moon revealed discrepancies of up to 10% in relative reflectance between images containing scattered light and images corrected for scattered light. Scattered light adds a wavelength-dependent low-intensity brightness factor to pixels across an image. For example, a large bright geological feature located just outside the field of view of an image will scatter extra light onto neighboring pixels within the field of view. Scattered light can be seen as a dim halo surrounding an image that includes a bright limb, and can also come from light scattered inside the camera by dirt, edges, and the interfaces of lenses. Because of the wavelength dependence of this effect, a scattered light correction must be performed on any SSI multispectral dataset before quantitative spectral analysis can be done. The process involves using a point-spread function for each filter that helps determine the amount of scattered light expected for a given pixel based on its location and the model attenuation factor for that pixel. To remove scattered light for a particular image taken through a particular filter, the Fourier transform of the attenuation function, which is the point spread function for that filter, is convolved with the Fourier transform of the image at the same wavelength. The result is then filtered for noise in the frequency domain, and then transformed back to the spatial domain. This results in a version of the original image that would have been taken without the scattered light contribution. We will report on our initial results from this calibration.
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Generalization of the Hartree-Fock approach to collision processes
NASA Astrophysics Data System (ADS)
Hahn, Yukap
1997-06-01
The conventional Hartree and Hartree-Fock approaches for bound states are generalized to treat atomic collision processes. All the single-particle orbitals, for both bound and scattering states, are determined simultaneously by requiring full self-consistency. This generalization is achieved by introducing two Ansäauttze: (a) the weak asymptotic boundary condition, which maintains the correct scattering energy and target orbitals with correct number of nodes, and (b) square integrable amputated scattering functions to generate self-consistent field (SCF) potentials for the target orbitals. The exact initial target and final-state asymptotic wave functions are not required and thus need not be specified a priori, as they are determined simultaneously by the SCF iterations. To check the asymptotic behavior of the solution, the theory is applied to elastic electron-hydrogen scattering at low energies. The solution is found to be stable and the weak asymptotic condition is sufficient to produce the correct scattering amplitudes. The SCF potential for the target orbital shows the strong penetration by the projectile electron during the collision, but the exchange term tends to restore the original form. Potential applicabilities of this extension are discussed, including the treatment of ionization and shake-off processes.
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Topographic correction realization based on the CBERS-02B image
NASA Astrophysics Data System (ADS)
Qin, Hui-ping; Yi, Wei-ning; Fang, Yong-hua
2011-08-01
The special topography of mountain terrain will induce the retrieval distortion in same species and surface spectral lines. In order to improve the research accuracy of topographic surface characteristic, many researchers have focused on topographic correction. Topographic correction methods can be statistical-empirical model or physical model, in which the methods based on the digital elevation model data are most popular. Restricted by spatial resolution, previous model mostly corrected topographic effect based on Landsat TM image, whose spatial resolution is 30 meter that can be easily achieved from internet or calculated from digital map. Some researchers have also done topographic correction based on high spatial resolution images, such as Quickbird and Ikonos, but there is little correlative research on the topographic correction of CBERS-02B image. In this study, liao-ning mountain terrain was taken as the objective. The digital elevation model data was interpolated to 2.36 meter by 15 meter original digital elevation model one meter by one meter. The C correction, SCS+C correction, Minnaert correction and Ekstrand-r were executed to correct the topographic effect. Then the corrected results were achieved and compared. The images corrected with C correction, SCS+C correction, Minnaert correction and Ekstrand-r were compared, and the scatter diagrams between image digital number and cosine of solar incidence angel with respect to surface normal were shown. The mean value, standard variance, slope of scatter diagram, and separation factor were statistically calculated. The analysed result shows that the shadow is weakened in corrected images than the original images, and the three-dimensional affect is removed. The absolute slope of fitting lines in scatter diagram is minished. Minnaert correction method has the most effective result. These demonstrate that the former correction methods can be successfully adapted to CBERS-02B images. The DEM data can be interpolated step by step to get the corresponding spatial resolution approximately for the condition that high spatial resolution elevation data is hard to get.
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On the far-field computation of acoustic radiation forces.
Martin, P A
2017-10-01
It is known that the steady acoustic radiation force on a scatterer due to incident time-harmonic waves can be calculated by evaluating certain integrals of velocity potentials over a sphere surrounding the scatterer. The goal is to evaluate these integrals using far-field approximations and appropriate limits. Previous derivations are corrected, clarified, and generalized. Similar corrections are made to textbook derivations of optical theorems.
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Corrections on energy spectrum and scatterings for fast neutron radiography at NECTAR facility
NASA Astrophysics Data System (ADS)
Liu, Shu-Quan; Bücherl, Thomas; Li, Hang; Zou, Yu-Bin; Lu, Yuan-Rong; Guo, Zhi-Yu
2013-11-01
Distortions caused by the neutron spectrum and scattered neutrons are major problems in fast neutron radiography and should be considered for improving the image quality. This paper puts emphasis on the removal of these image distortions and deviations for fast neutron radiography performed at the NECTAR facility of the research reactor FRM- II in Technische Universität München (TUM), Germany. The NECTAR energy spectrum is analyzed and established to modify the influence caused by the neutron spectrum, and the Point Scattered Function (PScF) simulated by the Monte-Carlo program MCNPX is used to evaluate scattering effects from the object and improve image quality. Good analysis results prove the sound effects of the above two corrections.
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SU-D-206-04: Iterative CBCT Scatter Shading Correction Without Prior Information
DOE Office of Scientific and Technical Information (OSTI.GOV)
Bai, Y; Wu, P; Mao, T
2016-06-15
Purpose: To estimate and remove the scatter contamination in the acquired projection of cone-beam CT (CBCT), to suppress the shading artifacts and improve the image quality without prior information. Methods: The uncorrected CBCT images containing shading artifacts are reconstructed by applying the standard FDK algorithm on CBCT raw projections. The uncorrected image is then segmented to generate an initial template image. To estimate scatter signal, the differences are calculated by subtracting the simulated projections of the template image from the raw projections. Since scatter signals are dominantly continuous and low-frequency in the projection domain, they are estimated by low-pass filteringmore » the difference signals and subtracted from the raw CBCT projections to achieve the scatter correction. Finally, the corrected CBCT image is reconstructed from the corrected projection data. Since an accurate template image is not readily segmented from the uncorrected CBCT image, the proposed scheme is iterated until the produced template is not altered. Results: The proposed scheme is evaluated on the Catphan©600 phantom data and CBCT images acquired from a pelvis patient. The result shows that shading artifacts have been effectively suppressed by the proposed method. Using multi-detector CT (MDCT) images as reference, quantitative analysis is operated to measure the quality of corrected images. Compared to images without correction, the method proposed reduces the overall CT number error from over 200 HU to be less than 50 HU and can increase the spatial uniformity. Conclusion: An iterative strategy without relying on the prior information is proposed in this work to remove the shading artifacts due to scatter contamination in the projection domain. The method is evaluated in phantom and patient studies and the result shows that the image quality is remarkably improved. The proposed method is efficient and practical to address the poor image quality issue of CBCT images. This work is supported by the Zhejiang Provincial Natural Science Foundation of China (Grant No. LR16F010001), National High-tech R&D Program for Young Scientists by the Ministry of Science and Technology of China (Grant No. 2015AA020917).« less
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Bistatic scattering from a cone frustum
NASA Technical Reports Server (NTRS)
Ebihara, W.; Marhefka, R. J.
1986-01-01
The bistatic scattering from a perfectly conducting cone frustum is investigated using the Geometrical Theory of Diffraction (GTD). The first-order GTD edge-diffraction solution has been extended by correcting for its failure in the specular region off the curved surface and in the rim-caustic regions of the endcaps. The corrections are accomplished by the use of transition functions which are developed and introduced into the diffraction coefficients. Theoretical results are verified in the principal plane by comparison with the moment method solution and experimental measurements. The resulting solution for the scattered fields is accurate, easy to apply, and fast to compute.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Abelof, Gabriel; Boughezal, Radja; Liu, Xiaohui
2016-10-17
We compute the Oσ 2σ 2 s perturbative corrections to inclusive jet production in electron-nucleon collisions. This process is of particular interest to the physics program of a future Electron Ion Collider (EIC). We include all relevant partonic processes, including deep-inelastic scattering contributions, photon-initiated corrections, and parton-parton scattering terms that first appear at this order. Upon integration over the final-state hadronic phase space we validate our results for the deep-inelastic corrections against the known next-to-next-to-leading order (NNLO) structure functions. Our calculation uses the N-jettiness subtraction scheme for performing higher-order computations, and allows for a completely differential description of the deep-inelasticmore » scattering process. We describe the application of this method to inclusive jet production in detail, and present phenomenological results for the proposed EIC. The NNLO corrections have a non-trivial dependence on the jet kinematics and arise from an intricate interplay between all contributing partonic channels.« less
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[Atmospheric correction of HJ-1 CCD data for water imagery based on dark object model].
Zhou, Li-Guo; Ma, Wei-Chun; Gu, Wan-Hua; Huai, Hong-Yan
2011-08-01
The CCD multi-band data of HJ-1A has great potential in inland water quality monitoring, but the precision of atmospheric correction is a premise and necessary procedure for its application. In this paper, a method based on dark pixel for water-leaving radiance retrieving is proposed. Beside the Rayleigh scattering, the aerosol scattering is important to atmospheric correction, the water quality of inland lakes always are case II water and the value of water leaving radiance is not zero. So the synchronous MODIS shortwave infrared data was used to obtain the aerosol parameters, and in virtue of the characteristic that aerosol scattering is relative stabilized in 560 nm, the water-leaving radiance for each visible and near infrared band were retrieved and normalized, accordingly the remotely sensed reflectance of water was computed. The results show that the atmospheric correction method based on the imagery itself is more effective for the retrieval of water parameters for HJ-1A CCD data.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Hawke, J.; Scannell, R.; Maslov, M.
2013-10-15
This work isolated the cause of the observed discrepancy between the electron temperature (T{sub e}) measurements before and after the JET Core LIDAR Thomson Scattering (TS) diagnostic was upgraded. In the upgrade process, stray light filters positioned just before the detectors were removed from the system. Modelling showed that the shift imposed on the stray light filters transmission functions due to the variations in the incidence angles of the collected photons impacted plasma measurements. To correct for this identified source of error, correction factors were developed using ray tracing models for the calibration and operational states of the diagnostic. Themore » application of these correction factors resulted in an increase in the observed T{sub e}, resulting in the partial if not complete removal of the observed discrepancy in the measured T{sub e} between the JET core LIDAR TS diagnostic, High Resolution Thomson Scattering, and the Electron Cyclotron Emission diagnostics.« less
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Le, Xuan T; Mai, Tam V T; Ratkiewicz, Artur; Huynh, Lam K
2015-04-23
This paper presents a computational study on the low-temperature mechanism and kinetics of the reaction between molecular oxygen and alkyl radicals of methyl propanoate (MP), which plays an important role in low-temperature oxidation and/or autoignition processes of the title fuel. Their multiple reaction pathways either accelerate the oxidation process via chain branching or inhibit it by forming relatively stable products. The potential energy surfaces of the reactions between three primary MP radicals and molecular oxygen, namely, C(•)H2CH2COOCH3 + O2, CH3C(•)HCOOCH3 + O2, and CH3CH2COOC(•)H2 + O2, were constructed using the accurate composite CBS-QB3 method. Thermodynamic properties of all species as well as high-pressure rate constants of all reaction channels were derived with explicit corrections for tunneling and hindered internal rotations. Our calculation results are in good agreement with a limited number of scattered data in the literature. Furthermore, pressure- and temperature-dependent rate constants for all reaction channels on the multiwell-multichannel potential energy surfaces were computed with the quantum Rice-Ramsperger-Kassel (QRRK) and the modified strong collision (MSC) theories. This procedure resulted in a thermodynamically consistent detailed kinetic submechanism for low-temperature oxidation governed by the title process. A simplified mechanism, which consists of important reactions, is also suggested for low-temperature combustion at engine-like conditions.
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Han, Bangxing; Peng, Huasheng; Yan, Hui
2016-01-01
Mugua is a common Chinese herbal medicine. There are three main medicinal origin places in China, Xuancheng City Anhui Province, Qijiang District Chongqing City, Yichang City, Hubei Province, and suitable for food origin places Linyi City Shandong Province. To construct a qualitative analytical method to identify the origin of medicinal Mugua by near infrared spectroscopy (NIRS). Partial least squares discriminant analysis (PLSDA) model was established after the Mugua derived from five different origins were preprocessed by the original spectrum. Moreover, the hierarchical cluster analysis was performed. The result showed that PLSDA model was established. According to the relationship of the origins-related important score and wavenumber, and K-mean cluster analysis, the Muguas derived from different origins were effectively identified. NIRS technology can quickly and accurately identify the origin of Mugua, provide a new method and technology for the identification of Chinese medicinal materials. After preprocessed by D1+autoscale, more peaks were increased in the preprocessed Mugua in the near infrared spectrumFive latent variable scores could reflect the information related to the origin place of MuguaOrigins of Mugua were well-distinguished according to K. mean value clustering analysis. Abbreviations used: TCM: Traditional Chinese Medicine, NIRS: Near infrared spectroscopy, SG: Savitzky-Golay smoothness, D1: First derivative, D2: Second derivative, SNV: Standard normal variable transformation, MSC: Multiplicative scatter correction, PLSDA: Partial least squares discriminant analysis, LV: Latent variable, VIP scores: Important score.
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NASA Astrophysics Data System (ADS)
Li, Cuiling; Jiang, Kai; Zhao, Xueguan; Fan, Pengfei; Wang, Xiu; Liu, Chuan
2017-10-01
Impurity of melon seeds variety will cause reductions of melon production and economic benefits of farmers, this research aimed to adopt spectral technology combined with chemometrics methods to identify melon seeds variety. Melon seeds whose varieties were "Yi Te Bai", "Yi Te Jin", "Jing Mi NO.7", "Jing Mi NO.11" and " Yi Li Sha Bai "were used as research samples. A simple spectral system was developed to collect reflective spectral data of melon seeds, including a light source unit, a spectral data acquisition unit and a data processing unit, the detection wavelength range of this system was 200-1100nm with spectral resolution of 0.14 7.7nm. The original reflective spectral data was pre-treated with de-trend (DT), multiple scattering correction (MSC), first derivative (FD), normalization (NOR) and Savitzky-Golay (SG) convolution smoothing methods. Principal Component Analysis (PCA) method was adopted to reduce the dimensions of reflective spectral data and extract principal components. K-nearest neighbour (KNN) and Fisher discriminant analysis (FDA) methods were used to develop discriminant models of melon seeds variety based on PCA. Spectral data pretreatments improved the discriminant effects of KNN and FDA, FDA generated better discriminant results than KNN, both KNN and FDA methods produced discriminant accuracies reaching to 90.0% for validation set. Research results showed that using spectral technology in combination with KNN and FDA modelling methods to identify melon seeds variety was feasible.
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Umbilical cord fibroblasts: Could they be considered as mesenchymal stem cells?
Zeddou, Mustapha; Relic, Biserka; Malaise, Michel G
2014-01-01
In cell therapy protocols, many tissues were proposed as a source of mesenchymal stem cells (MSC) isolation. So far, bone marrow (BM) has been presented as the main source of MSC despite the invasive isolation procedure related to this source. During the last years, the umbilical cord (UC) matrix was cited in different studies as a reliable source from which long term ex vivo proliferating fibroblasts were isolated but with contradictory data about their immunophenotype, gene expression profile, and differentiation potential. Hence, an interesting question emerged: Are cells isolated from cord matrix (UC-MSC) different from other MSCs? In this review, we will summarize different studies that isolated and characterized UC-MSC. Considering BM-MSC as gold standard, we will discuss if UC-MSC fulfill different criteria that define MSC, and what remain to be done in this issue. PMID:25126385
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Use of Small Fluorescent Molecules to Monitor Channel Activity
NASA Astrophysics Data System (ADS)
Jones, Sharon; Stringer, Sarah; Naik, Rajesh; Stone, Morley
2001-03-01
The Mechanosensitive channel of Large conductance (MscL) allows bacteria to rapidly adapt to changing environmental conditions such as osmolarity. The MscL channel opens in response to increases in membrane tension, which allows for the efflux of cytoplasmic constituents. Here we describe the cloning and expression of Salmonella typhimurium MscL (St-MscL). Using a fluorescence efflux assay, we demonstrate that efflux through the MscL channel during hypoosmotic shock can be monitored using endogenously produced fluorophores. In addition, we observe that thermal stimulation, i.e., heat shock, can also induce efflux through MscL. We present the first evidence of thermal activation of MscL efflux by heat shocking cells expressing the S. typhimurium protein variant. This finding has significant biosensor implications, especially for investigators exploring the use of channel proteins in biosensor applications. Thermal biosensors are relatively unexplored, but would have considerable commercial and military utility.
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Yang, Zijiang; Concannon, John; Ng, Kelvin S; Seyb, Kathleen; Mortensen, Luke J; Ranganath, Sudhir; Gu, Fangqi; Levy, Oren; Tong, Zhixiang; Martyn, Keir; Zhao, Weian; Lin, Charles P; Glicksman, Marcie A; Karp, Jeffrey M
2016-07-26
Pre-treatment or priming of mesenchymal stem cells (MSC) prior to transplantation can significantly augment the immunosuppressive effect of MSC-based therapies. In this study, we screened a library of 1402 FDA-approved bioactive compounds to prime MSC. We identified tetrandrine as a potential hit that activates the secretion of prostaglandin E2 (PGE2), a potent immunosuppressive agent, by MSC. Tetrandrine increased MSC PGE2 secretion through the NF-κB/COX-2 signaling pathway. When co-cultured with mouse macrophages (RAW264.7), tetrandrine-primed MSC attenuated the level of TNF-α secreted by RAW264.7. Furthermore, systemic transplantation of primed MSC into a mouse ear skin inflammation model significantly reduced the level of TNF-α in the inflamed ear, compared to unprimed cells. Screening of small molecules to pre-condition cells prior to transplantation represents a promising strategy to boost the therapeutic potential of cell therapy.
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MSC products for the simulation of tire behavior
NASA Technical Reports Server (NTRS)
Muskivitch, John C.
1995-01-01
The modeling of tires and the simulation of tire behavior are complex problems. The MacNeal-Schwendler Corporation (MSC) has a number of finite element analysis products that can be used to address the complexities of tire modeling and simulation. While there are many similarities between the products, each product has a number of capabilities that uniquely enable it to be used for a specific aspect of tire behavior. This paper discusses the following programs: (1) MSC/NASTRAN - general purpose finite element program for linear and nonlinear static and dynamic analysis; (2) MSC/ADAQUS - nonlinear statics and dynamics finite element program; (3) MSC/PATRAN AFEA (Advanced Finite Element Analysis) - general purpose finite element program with a subset of linear and nonlinear static and dynamic analysis capabilities with an integrated version of MSC/PATRAN for pre- and post-processing; and (4) MSC/DYTRAN - nonlinear explicit transient dynamics finite element program.
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Sundin, Mikael; Lindblom, Anna; Örvell, Claes; Barrett, A.John; Sundberg, Berit; Watz, Emma; Wikman, Agneta; Broliden, Kristina; Le Blanc, Katarina
2014-01-01
Multipotent mesenchymal stromal cells (MSC) are used to improve the outcome of hematopoietic stem cell transplantation and in regenerative medicine. However, MSC may harbor persistent viruses that may compromise their clinical benefit. Retrospectively screened, 1 of 20 MSC from healthy donors contained parvovirus B19 (B19) DNA. We found that MSC express the B19 receptor (the globoside P antigen) and a co-receptor (Ku 80), and can transmit B19 to bone marrow cells in vitro, suggesting that the virus can persist in the marrow stroma of healthy individuals. Two stem cell transplant patients received the B19 positive MSC as treatment for graft-versus-host disease. Neither developed viremia nor symptomatic B19 infection. These results demonstrate for the first time that persistent B19 in MSC can infect hematopoietic cells and underscore the importance of monitoring B19 transmission by MSC products. PMID:18804048
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View of Mission Control Center celebrating conclusion of Apollo 11 mission
NASA Technical Reports Server (NTRS)
1969-01-01
Overall view of the Mission Operations Control Room in the Mission Control Center, bldg 30, Manned Spacecraft Center (MSC), at the conclusion of the Apollo 11 lunar landing mission. The television monitor shows President Richard M. Nixon greeting the Apollo 11 astronauts aboard the U.S.S. Hornet in the Pacific recovery area (40301); NASA and MSC Officials join the flight controllers in celebrating the conclusion of the Apollo 11 mission. From left foreground Dr. Maxime A. Faget, MSC Director of Engineering and Development; George S. Trimble, MSC Deputy Director; Dr. Christopher C. Kraft Jr., MSC Director fo Flight Operations; Julian Scheer (in back), Assistant Adminstrator, Offic of Public Affairs, NASA HQ.; George M. Low, Manager, Apollo Spacecraft Program, MSC; Dr. Robert R. Gilruth, MSC Director; and Charles W. Mathews, Deputy Associate Administrator, Office of Manned Space Flight, NASA HQ (40302).
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Confirming the Revised C-Terminal Domain of the MscL Crystal Structure
Maurer, Joshua A.; Elmore, Donald E.; Clayton, Daniel; Xiong, Li; Lester, Henry A.; Dougherty, Dennis A.
2008-01-01
The structure of the C-terminal domain of the mechanosensitive channel of large conductance (MscL) has generated significant controversy. As a result, several structures have been proposed for this region: the original crystal structure (1MSL) of the Mycobacterium tuberculosis homolog (Tb), a model of the Escherichia coli homolog, and, most recently, a revised crystal structure of Tb-MscL (2OAR). To understand which of these structures represents a physiological conformation, we measured the impact of mutations to the C-terminal domain on the thermal stability of Tb-MscL using circular dichroism and performed molecular dynamics simulations of the original and the revised crystal structures of Tb-MscL. Our results imply that this region is helical and adopts an α-helical bundle conformation similar to that observed in the E. coli MscL model and the revised Tb-MscL crystal structure. PMID:18326638
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Plasmonic SERS nanochips and nanoprobes for medical diagnostics and bio-energy applications
NASA Astrophysics Data System (ADS)
Ngo, Hoan T.; Wang, Hsin-Neng; Crawford, Bridget M.; Fales, Andrew M.; Vo-Dinh, Tuan
2017-02-01
The development of rapid, easy-to-use, cost-effective, high accuracy, and high sensitive DNA detection methods for molecular diagnostics has been receiving increasing interest. Over the last five years, our laboratory has developed several chip-based DNA detection techniques including the molecular sentinel-on-chip (MSC), the multiplex MSC, and the inverse molecular sentinel-on-chip (iMS-on-Chip). In these techniques, plasmonic surface-enhanced Raman scattering (SERS) Nanowave chips were functionalized with DNA probes for single-step DNA detection. Sensing mechanisms were based on hybridization of target sequences and DNA probes, resulting in a distance change between SERS reporters and the Nanowave chip's gold surface. This distance change resulted in change in SERS intensity, thus indicating the presence and capture of the target sequences. Our techniques were single-step DNA detection techniques. Target sequences were detected by simple delivery of sample solutions onto DNA probe-functionalized Nanowave chips and SERS signals were measured after 1h - 2h incubation. Target sequence labeling or washing to remove unreacted components was not required, making the techniques simple, easy-to-use, and cost effective. The usefulness of the techniques for medical diagnostics was illustrated by the detection of genetic biomarkers for respiratory viral infection and of dengue virus 4 DNA.
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Mrs. Haise in viewing room overlooking FCR
1970-04-14
S70-34900 (14 April 1970) --- Mrs. Mary Haise receives an explanation of the revised flight plan of the Apollo 13 mission from astronaut Gerald P. Carr in the viewing room of the Mission Control Center (MCC), Building 30, at the Manned Spacecraft Center (MSC). Her husband, astronaut Fred W. Haise Jr., lunar module pilot for the Apollo 13 mission, was joining fellow crew members, astronauts James A. Lovell Jr., and John L. Swigert Jr. in making correction in their spacecraft following discovery of an oxygen cell failure several hours earlier.
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Human umbilical cord mesenchymal stem cells increase interleukin-9 production of CD4+ T cells
Yang, Zhou Xin; Chi, Ying; Ji, Yue Ru; Wang, You Wei; Zhang, Jing; Luo, Wei Feng; Li, Li Na; Hu, Cai Dong; Zhuo, Guang Sheng; Wang, Li Fang; Han, Zhi-Bo; Han, Zhong Chao
2017-01-01
Mesenchymal stem cells (MSC) are able to differentiate into cells of multiple lineage, and additionally act to modulate the immune response. Interleukin (IL)-9 is primarily produced by cluster of differentiation (CD)4+ T cells to regulate the immune response. The present study aimed to investigate the effect of human umbilical cord derived-MSC (UC-MSC) on IL-9 production of human CD4+ T cells. It was demonstrated that the addition of UC-MSC to the culture of CD4+ T cells significantly enhanced IL-9 production by CD4+ T cells. Transwell experiments suggested that UC-MSC promotion of IL-9 production by CD4+ T cells was dependent on cell-cell contact. Upregulated expression of CD106 was observed in UC-MSC co-cultured with CD4+ T cells, and the addition of a blocking antibody of CD106 significantly impaired the ability of UC-MSC to promote IL-9 production by CD4+ T cells. Therefore, the results of the present study demonstrated that UC-MSC promoted the generation of IL-9 producing cells, which may be mediated, in part by CD106. The findings may act to expand understanding and knowledge of the immune modulatory role of UC-MSC. PMID:29042945
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Meng, Xin; Li, Jianping; Yu, Ming; Yang, Jian; Zheng, Minjuan; Zhang, Jinzhou; Sun, Chao; Liang, Hongliang; Liu, Liwen
2018-01-01
Mesenchymal stem cell (MSC) has been well known to exert therapeutic potential for patients with myocardial infarction (MI). In addition, interleukin-10 (IL10) could attenuate MI through suppressing inflammation. Thus, the combination of MSC implantation with IL10 delivery may extend health benefits to ameliorate cardiac injury after MI. Here we established overexpression of IL10 in bone marrow-derived MSC through adenoviral transduction. Cell viability, apoptosis, and IL10 secretion under ischemic challenge in vitro were examined. In addition, MSC was transplanted into the injured hearts in a rat model of MI. Four weeks after the MI induction, MI, cardiac functions, apoptotic cells, and inflammation cytokines were assessed. In response to in vitro oxygen-glucose deprivation (OGD), IL10 overexpression in MSC (Ad.IL10-MSC) enhanced cell viability, decreased apoptosis, and increased IL10 secretion. Consistently, the implantation of Ad.IL10-MSCs into MI animals resulted in more reductions in myocardial infarct size, cardiac impairment, and cell apoptosis, compared to the individual treatments of either MSC or IL10 administration. Moreover, the attenuation of both systemic and local inflammations was most prominent for Ad.IL10-MSC treatment. IL10 overexpression and MSC may exert a synergistic anti-inflammatory effect to alleviate cardiac injury after MI. © 2017 Wiley Periodicals, Inc.
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Synergistic Effects of GDNF and VEGF on Lifespan and Disease Progression in a Familial ALS Rat Model
Krakora, Dan; Mulcrone, Patrick; Meyer, Michael; Lewis, Christina; Bernau, Ksenija; Gowing, Genevieve; Zimprich, Chad; Aebischer, Patrick; Svendsen, Clive N; Suzuki, Masatoshi
2013-01-01
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the progressive loss of motor neurons in the brain and spinal cord. We have recently shown that human mesenchymal stem cells (hMSCs) modified to release glial cell line-derived neurotrophic factor (GDNF) decrease disease progression in a rat model of ALS when delivered to skeletal muscle. In the current study, we determined whether or not this effect could be enhanced by delivering GDNF in concert with other trophic factors. hMSC engineered to secrete GDNF (hMSC-GDNF), vascular endothelial growth factor (hMSC-VEGF), insulin-like growth factor-I (hMSC-IGF-I), or brain-derived neurotrophic factor (hMSC-BDNF), were prepared and transplanted bilaterally into three muscle groups. hMSC-GDNF and hMSC-VEGF prolonged survival and slowed the loss of motor function, but hMSC-IGF-I and hMSC-BDNF did not have any effect. We then tested the efficacy of a combined ex vivo delivery of GDNF and VEGF in extending survival and protecting neuromuscular junctions (NMJs) and motor neurons. Interestingly, the combined delivery of these neurotrophic factors showed a strong synergistic effect. These studies further support ex vivo gene therapy approaches for ALS that target skeletal muscle. PMID:23712039
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Septal penetration correction in I-131 imaging following thyroid cancer treatment
NASA Astrophysics Data System (ADS)
Barrack, Fiona; Scuffham, James; McQuaid, Sarah
2018-04-01
Whole body gamma camera images acquired after I-131 treatment for thyroid cancer can suffer from collimator septal penetration artefacts because of the high energy of the gamma photons. This results in the appearance of ‘spoke’ artefacts, emanating from regions of high activity concentration, caused by the non-isotropic attenuation of the collimator. Deconvolution has the potential to reduce such artefacts, by taking into account the non-Gaussian point-spread-function (PSF) of the system. A Richardson–Lucy deconvolution algorithm, with and without prior scatter-correction was tested as a method of reducing septal penetration in planar gamma camera images. Phantom images (hot spheres within a warm background) were acquired and deconvolution using a measured PSF was applied. The results were evaluated through region-of-interest and line profile analysis to determine the success of artefact reduction and the optimal number of deconvolution iterations and damping parameter (λ). Without scatter-correction, the optimal results were obtained with 15 iterations and λ = 0.01, with the counts in the spokes reduced to 20% of the original value, indicating a substantial decrease in their prominence. When a triple-energy-window scatter-correction was applied prior to deconvolution, the optimal results were obtained with six iterations and λ = 0.02, which reduced the spoke counts to 3% of the original value. The prior application of scatter-correction therefore produced the best results, with a marked change in the appearance of the images. The optimal settings were then applied to six patient datasets, to demonstrate its utility in the clinical setting. In all datasets, spoke artefacts were substantially reduced after the application of scatter-correction and deconvolution, with the mean spoke count being reduced to 10% of the original value. This indicates that deconvolution is a promising technique for septal penetration artefact reduction that could potentially improve the diagnostic accuracy of I-131 imaging. Novelty and significance This work has demonstrated that scatter correction combined with deconvolution can be used to substantially reduce the appearance of septal penetration artefacts in I-131 phantom and patient gamma camera planar images, enable improved visualisation of the I-131 distribution. Deconvolution with symmetric PSF has previously been used to reduce artefacts in gamma camera images however this work details the novel use of an asymmetric PSF to remove the angularly dependent septal penetration artefacts.
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Kucerova, L; Skolekova, S; Demkova, L; Bohovic, R; Matuskova, M
2014-10-01
Mesenchymal stromal cells (MSC) can be exploited as cellular delivery vehicles for the enzymes converting non-toxic prodrugs to toxic substances. Because of their inherent chemoresistance, they exert potent bystander and antitumor effect. Here we show that the human adipose tissue-derived MSC expressing fusion yeast cytosine deaminase::uracil phosphoribosyltransferase (CD-MSC) in combination with 5-fluorocytosine (5FC) mediated a long-term tumor-free survival in the 83.3% of tumor-bearing animals. CD-MSC/5FC treatment induced cytotoxicity against model human melanoma cells EGFP-A375. Only 4% of the therapeutic CD-MSC cells eliminated >98.5% of the tumor cells in vitro. Long-term tumor-free survival was confirmed in 15 out of the 18 animals. However, repeatedly used CD-MSC/5FC therapeutic regimen generated more aggressive and metastatic variant of the melanoma cells EGFP-A375/Rel3. These cells derived from the refractory xenotransplants exhibited increased resistance to the CD-MSC/5FC treatment, altered cell adhesion, migration, tumorigenic and metastatic properties. However, long-term curative effect was achieved by the augmentation of the CD-MSC/5FC regimen along with the inhibition of c-Met/hepatocyte growth factor signaling axis in this aggressive melanoma derivative. In summary, the CD-MSC/5FC regimen can be regarded as a very effective antitumor approach to achieve long-term tumor-free survival as demonstrated on a mouse model of aggressive human melanoma xenografts.
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Han, Juhee; Mistriotis, Panagiotis; Lei, Pedro; Wang, Dan; Liu, Song; Andreadis, Stelios T.
2012-01-01
Although the therapeutic potential of mesenchymal stem cells (MSC) is widely accepted, loss of cell function due to donor aging or culture senescence are major limiting factors hampering their clinical application. Our laboratory recently showed that MSC originating from older donors suffer from limited proliferative capacity and significantly reduced myogenic differentiation potential. This is a major concern, as the patients most likely to suffer from cardiovascular disease are elderly. Here we tested the hypothesis that a single pluripotency associated transcription factor, namely Nanog, may reverse the proliferation and differentiation potential of BM-MSC from adult donors. Microarray analysis showed that adult (a)BM-MSC expressing Nanog clustered close to Nanog-expressing neonatal cells. Nanog markedly upregulated genes involved in cell cycle, DNA replication and DNA damage repair and enhanced the proliferation rate and clonogenic capacity of aBM-MSC. Notably, Nanog reversed the myogenic differentiation potential and restored the contractile function of aBM-MSC to a similar level as that of neonatal (n)BM-MSC. The effect of Nanog on contractility was mediated – at least in part - through activation of the TGF-β pathway by diffusible factors secreted in the conditioned medium of Nanog-expressing BM-MSC. Overall, our results suggest that Nanog may be used to overcome the effects of organismal aging on aBM-MSC, thereby increasing the potential of MSC from aged donors for cellular therapy and tissue regeneration. PMID:22949105
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Exosomes Derived from Mesenchymal Stromal Cells Promote Axonal Growth of Cortical Neurons.
Zhang, Yi; Chopp, Michael; Liu, Xian Shuang; Katakowski, Mark; Wang, Xinli; Tian, Xinchu; Wu, David; Zhang, Zheng Gang
2017-05-01
Treatment of brain injury with exosomes derived from mesenchymal stromal cells (MSCs) enhances neurite growth. However, the direct effect of exosomes on axonal growth and molecular mechanisms underlying exosome-enhanced neurite growth are not known. Using primary cortical neurons cultured in a microfluidic device, we found that MSC-exosomes promoted axonal growth, whereas attenuation of argonaut 2 protein, one of the primary microRNA (miRNA) machinery proteins, in MSC-exosomes abolished their effect on axonal growth. Both neuronal cell bodies and axons internalized MSC-exosomes, which was blocked by botulinum neurotoxins (BoNTs) that cleave proteins of the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex. Moreover, tailored MSC-exosomes carrying elevated miR-17-92 cluster further enhanced axonal growth compared to native MSC-exosomes. Quantitative RT-PCR and Western blot analysis showed that the tailored MSC-exosomes increased levels of individual members of this cluster and activated the PTEN/mTOR signaling pathway in recipient neurons, respectively. Together, our data demonstrate that native MSC-exosomes promote axonal growth while the tailored MSC-exosomes can further boost this effect and that tailored exosomes can deliver their selective cargo miRNAs into and activate their target signals in recipient neurons. Neuronal internalization of MSC-exosomes is mediated by the SNARE complex. This study reveals molecular mechanisms that contribute to MSC-exosome-promoted axonal growth, which provides a potential therapeutic strategy to enhance axonal growth.
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Immunomodulatory Properties of Induced Pluripotent Stem Cell-Derived Mesenchymal Cells.
Ng, Jia; Hynes, Kim; White, Gregory; Sivanathan, Kisha Nandini; Vandyke, Kate; Bartold, Peter Mark; Gronthos, Stan
2016-12-01
MSC-like populations derived from induced pluripotent stem cells (iPSC-MSC) serve as an alternative stem cell source due to their high proliferative capacity. In this study, we assessed the immunomodulatory potential of iPSC-MSC generated from periodontal ligament (PDL) and gingival (GF) tissue. The iPSC-MSC lines exhibited a similar level of suppression of mitogen-stimulated peripheral blood mononuclear cells (PBMNC) proliferation compared to their respective parental fibroblast populations in vitro. Moreover, iPSC-MSC demonstrated the ability to suppress T-cells effector cells, Th1/Th2/Th17 populations, and increase levels of Treg cells. In order to investigate the mechanisms involved, expression of common MSC-derived soluble factors known to supress lymphocyte proliferation were assessed in iPSC-MSC cultured with PBMNC with direct cell-cell contact or separated in transwells. Real-time PCR analysis of factors known to be involved in MSC mediated immune regulation, found a general trend of elevated IDO1 and IL6 transcript levels in iPSC-MSC lines and their respective primary cells co-cultured with activated PBMNC, with a wide range of gene expression levels between the different mesenchymal cell types. The results suggest that different iPSC-MSC may be useful as a potential alternative source of cells for future clinical use in therapeutic applications because of their potent immunosuppressive properties. J. Cell. Biochem. 117: 2844-2853, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.
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Estrogenic effects of marijuana smoke condensate and cannabinoid compounds
DOE Office of Scientific and Technical Information (OSTI.GOV)
Lee, Soo Yeun; Sungkyunkwan University, 300 Cheoncheon-dong, Jangan-gu, Suwon, Gyeonggi-do 440-746; Oh, Seung Min
Chronic exposure to marijuana produces adverse effects on the endocrine and reproductive systems in humans; however, the experimental evidence for this presented thus far has not been without controversy. In this study, the estrogenic effect of marijuana smoke condensate (MSC) was evaluated using in vitro bioassays, viz., the cell proliferation assay, the reporter gene assay, and the ER competitive binding assay. The results of these assays were compared with those of three major cannabinoids, i.e., THC, CBD, and CBN. The estrogenic effect of MSC was further confirmed by the immature female rat uterotrophic assay. MSC stimulated the estrogenicity related tomore » the ER-mediated pathway, while neither THC, CBD, nor CBN did. Moreover, treatment with 10 and 25 mg/kg MSC induced significant uterine response, and 10 mg/kg MSC resulted in an obvious change in the uterine epithelial cell appearance. MSC also enhanced the IGFBP-1 gene expression in a dose-dependent manner. To identify the constituents of MSC responsible for its estrogenicity, the MSC fractionated samples were examined using another cell proliferation assay, and the estrogenic active fraction was analyzed using GC-MS. In the organic acid fraction that showed the strongest estrogenic activity among the seven fractions of MSC, phenols were identified. Our results suggest that marijuana abuse is considered an endocrine-disrupting factor. Furthermore, these results suggest that the phenolic compounds contained in MSC play a role in its estrogenic effect.« less
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Attenuation of aortic aneurysms with stem cells from different genders.
Davis, John P; Salmon, Morgan; Pope, Nicolas H; Lu, Guanyi; Su, Gang; Sharma, Ashish K; Ailawadi, Gorav; Upchurch, Gilbert R
2015-11-01
No medical therapies are yet available to slow abdominal aortic aneurysm (AAA) growth. This study sought to investigate the effect of different genders of bone marrow-derived mesenchymal stem cells (MSC) on AAA growth in a murine AAA model. Given the decreased rate of AAA in women, it is hypothesized that female MSC would attenuate AAA growth more so than male MSC. Aortas of 8-10-wk-old male C57Bl/6 mice were perfused with purified porcine pancreatic elastase to induce AAA formation. Bone marrow-derived MSC from male and female mice were dosed via tail vein injection (3 million cells per dose, 500 μL of volume per injection) on postaortic perfusion days 1, 3, and 5. Aortas were harvested after 14 d. Mean aortic dilation in the elastase group was 121 ± 5.2% (mean ± standard error of the mean), while male MSC inhibited AAA growth (87.8 ± 6.9%, P = 0.008) compared with that of elastase. Female MSC showed the most marked attenuation of AAA growth (75.2 ± 8.3% P = 0.0004). Proinflammatory cytokines tumor necrosis factor α, interleukin 1β, and monocyte chemotactic protein-1 (MCP-1) were only decreased in tissues treated with female MSC (P = 0.017, P = 0.001, and P < 0.0001, respectively, when compared with elastase). These data exhibit that female MSC more strongly attenuate AAA growth in the murine model. Furthermore, female MSC and male MSC inhibit proinflammatory cytokines at varying levels. The effects of MSC on aortic tissue offer a promising insight into biologic therapies for future medical treatment of AAAs in humans. Copyright © 2015 Elsevier Inc. All rights reserved.
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Parashurama, Natesh; Ahn, Byeong-Cheol; Ziv, Keren; Ito, Ken; Paulmurugan, Ramasamy; Willmann, Jürgen K.; Chung, Jaehoon; Ikeno, Fumiaki; Swanson, Julia C.; Merk, Denis R.; Lyons, Jennifer K.; Yerushalmi, David; Teramoto, Tomohiko; Kosuge, Hisanori; Dao, Catherine N.; Ray, Pritha; Patel, Manishkumar; Chang, Ya-fang; Mahmoudi, Morteza; Cohen, Jeff Eric; Goldstone, Andrew Brooks; Habte, Frezghi; Bhaumik, Srabani; Yaghoubi, Shahriar; Robbins, Robert C.; Dash, Rajesh; Yang, Phillip C.; Brinton, Todd J.; Yock, Paul G.; McConnell, Michael V.
2016-01-01
Purpose To use multimodality reporter-gene imaging to assess the serial survival of marrow stromal cells (MSC) after therapy for myocardial infarction (MI) and to determine if the requisite preclinical imaging end point was met prior to a follow-up large-animal MSC imaging study. Materials and Methods Animal studies were approved by the Institutional Administrative Panel on Laboratory Animal Care. Mice (n = 19) that had experienced MI were injected with bone marrow–derived MSC that expressed a multimodality triple fusion (TF) reporter gene. The TF reporter gene (fluc2-egfp-sr39ttk) consisted of a human promoter, ubiquitin, driving firefly luciferase 2 (fluc2), enhanced green fluorescent protein (egfp), and the sr39tk positron emission tomography reporter gene. Serial bioluminescence imaging of MSC-TF and ex vivo luciferase assays were performed. Correlations were analyzed with the Pearson product-moment correlation, and serial imaging results were analyzed with a mixed-effects regression model. Results Analysis of the MSC-TF after cardiac cell therapy showed significantly lower signal on days 8 and 14 than on day 2 (P = .011 and P = .001, respectively). MSC-TF with MI demonstrated significantly higher signal than MSC-TF without MI at days 4, 8, and 14 (P = .016). Ex vivo luciferase activity assay confirmed the presence of MSC-TF on days 8 and 14 after MI. Conclusion Multimodality reporter-gene imaging was successfully used to assess serial MSC survival after therapy for MI, and it was determined that the requisite preclinical imaging end point, 14 days of MSC survival, was met prior to a follow-up large-animal MSC study. © RSNA, 2016 Online supplemental material is available for this article. PMID:27308957
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Evangelista, Afrânio Ferreira; Vannier-Santos, Marcos André; de Assis Silva, Gessica Sabrina; Silva, Daniela Nascimento; Juiz, Paulo José Lima; Nonaka, Carolina Kymie Vasques; Dos Santos, Ricardo Ribeiro; Soares, Milena Botelho Pereira; Villarreal, Cristiane Flora
2018-06-22
Diabetic neuropathy (DN) is a frequent and debilitating manifestation of diabetes mellitus, to which there are no effective therapeutic approaches. Mesenchymal stem/stromal cells (MSC) have a great potential for the treatment of this syndrome, possibly through regenerative actions on peripheral nerves. Here, we evaluated the therapeutic effects of MSC on spinal neuroinflammation, as well as on ultrastructural aspects of the peripheral nerve in DN-associated sensorial dysfunction. C57Bl/6 mice were treated with bone marrow-derived MSC (1 × 10 6 ), conditioned medium from MSC cultures (CM-MSC) or vehicle by endovenous route following the onset of streptozotocin (STZ)-induced diabetes. Paw mechanical and thermal nociceptive thresholds were evaluated by using von Frey filaments and Hargreaves test, respectively. Morphological and morphometric analysis of the sciatic nerve was performed by light microscopy and transmission electron microscopy. Mediators and markers of neuroinflammation in the spinal cord were measured by radioimmunoassay, real-time PCR, and immunofluorescence analyses. Diabetic mice presented behavioral signs of sensory neuropathy, mechanical allodynia, and heat hypoalgesia, which were completely reversed by a single administration of MSC or CM-MSC. The ultrastructural analysis of the sciatic nerve showed that diabetic mice exhibited morphological and morphometric alterations, considered hallmarks of DN, such as degenerative changes in axons and myelin sheath, and reduced area and density of unmyelinated fibers. In MSC-treated mice, these structural alterations were markedly less commonly observed and/or less pronounced. Moreover, MSC transplantation inhibited multiple parameters of spinal neuroinflammation found in diabetic mice, causing the reduction of activated astrocytes and microglia, oxidative stress signals, galectin-3, IL-1β, and TNF-α production. Conversely, MSC increased the levels of anti-inflammatory cytokines, IL-10, and TGF-β. The present study described the modulatory effects of MSC on spinal cord neuroinflammation in diabetic mice, suggesting new mechanisms by which MSC can improve DN.
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Zhu, Yu; Wang, Yuchen; Zhao, Bizeng; Niu, Xin; Hu, Bin; Li, Qing; Zhang, Juntao; Ding, Jian; Chen, Yunfeng; Wang, Yang
2017-03-09
Osteoarthritis (OA) is the most common joint disease worldwide. In the past decade, mesenchymal stem cells (MSCs) have been used widely for the treatment of OA. A potential mechanism of MSC-based therapies has been attributed to the paracrine secretion of trophic factors, in which exosomes may play a major role. In this study, we aimed to compare the effectiveness of exosomes secreted by synovial membrane MSCs (SMMSC-Exos) and exosomes secreted by induced pluripotent stem cell-derived MSCs (iMSC-Exos) on the treatment of OA. Induced pluripotent stem cell-derived MSCs and synovial membrane MSCs were characterized by flow cytometry. iMSC-Exos and SMMSC-Exos were isolated using an ultrafiltration method. Tunable resistive pulse-sensing analysis, transmission electron microscopy, and western blots were used to identify exosomes. iMSC-Exos and SMMSC-Exos were injected intra-articularly in a mouse model of collagenase-induced OA and the efficacy of exosome injections was assessed by macroscopic, histological, and immunohistochemistry analysis. We also evaluated the effects of iMSC-Exos and SMMSC-Exos on proliferation and migration of human chondrocytes by cell-counting and scratch assays, respectively. The majority of iMSC-Exos and SMMSC-Exos were approximately 50-150 nm in diameter and expressed CD9, CD63, and TSG101. The injection of iMSC-Exos and SMMSC-Exos both attenuated OA in the mouse OA model, but iMSC-Exos had a superior therapeutic effect compared with SMMSC-Exos. Similarly, chondrocyte migration and proliferation were stimulated by both iMSC-Exos and SMMSC-Exos, with iMSC-Exos exerting a stronger effect. The present study demonstrated that iMSC-Exos have a greater therapeutic effect on OA than SMMSC-Exos. Because autologous iMSCs are theoretically inexhaustible, iMSC-Exos may represent a novel therapeutic approach for the treatment of OA.
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Tyciakova, Silvia; Matuskova, Miroslava; Bohovic, Roman; Polakova, Katarina; Toro, Lenka; Skolekova, Svetlana; Kucerova, Lucia
2015-01-01
Mesenchymal stromal cells (MSC) are a promising tool for targeted cancer therapy due to their tumour-homing ability. Intrinsic resistance enables the MSC to longer tolerate therapeutic factors, such as prodrug converting enzymes, cytokines and pro-apoptotic proteins. Tumour necrosis factor alpha (TNFα) is known to be cytotoxic to a variety of cancer cells and exert a tumour-destructive capacity. MSC were retrovirally transduced to stable express an exogenous gene encoding the desired therapeutic agent hTNFα. The effect of a TNFα-producing adipose tissue-derived MSC (AT-MSC/hTNFα) was tested on the tumour cell lines of different origins: melanoma (A375), breast carcinoma (SKBR3, MDA-MB-231), colon carcinoma (HT29), ovarian carcinoma (SKOV3) and glioblastoma (U87-MG) cells. The tumour suppressing effect of AT-MSC/hTNFα on A375 melanoma xenografts was monitored in an immunodeficient mouse model in vivo. Engineered AT-MSC are able to constitutively secrete human TNFα protein, induce apoptosis of tumour cell lines via caspase 3/7 activation and inhibit the tumour cell proliferation in vitro. Melanoma A375 and breast carcinoma SKBR3 cells were the most sensitive, and their proliferation in vitro was reduced by conditioned media produced by AT-MSC/hTNFα to 60% and 40%, respectively. The previously reported tumour supportive effect of AT-MSC on subcutaneous A375 melanoma xenograft growth was neutralised and suppressed by engineered AT-MSC stably producing hTNFα. When AT-MSC/hTNFα were coinjected with A375 melanoma cells, the tumour mass inhibition was up to 97.5%. The results of the present study demonstrate that tumour cells respond to hTNFα-based treatment mediated by genetically engineered AT-MSC/hTNFα both in vitro and in vivo. Copyright © 2015 John Wiley & Sons, Ltd.
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Surface areas of fractally rough particles studied by scattering
NASA Astrophysics Data System (ADS)
Hurd, Alan J.; Schaefer, Dale W.; Smith, Douglas M.; Ross, Steven B.; Le Méhauté, Alain; Spooner, Steven
1989-05-01
The small-angle scattering from fractally rough surfaces has the potential to give information on the surface area at a given resolution. By use of quantitative neutron and x-ray scattering, a direct comparison of surface areas of fractally rough powders was made between scattering and adsorption techniques. This study supports a recently proposed correction to the theory for scattering from fractal surfaces. In addition, the scattering data provide an independent calibration of molecular adsorbate areas.
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A Novel Corynebacterium glutamicum l-Glutamate Exporter.
Wang, Yu; Cao, Guoqiang; Xu, Deyu; Fan, Liwen; Wu, Xinyang; Ni, Xiaomeng; Zhao, Shuxin; Zheng, Ping; Sun, Jibin; Ma, Yanhe
2018-03-15
Besides metabolic pathways and regulatory networks, transport systems are also pivotal for cellular metabolism and hyperproduction of biochemicals using microbial cell factories. The identification and characterization of transporters are therefore of great significance for the understanding and engineering of transport reactions. Herein, a novel l-glutamate exporter, MscCG2, which exists extensively in Corynebacterium glutamicum strains but is distinct from the only known l-glutamate exporter, MscCG, was discovered in an industrial l-glutamate-producing C. glutamicum strain. MscCG2 was predicted to possess three transmembrane helices in the N-terminal region and located in the cytoplasmic membrane, which are typical structural characteristics of the mechanosensitive channel of small conductance. MscCG2 has a low amino acid sequence identity (23%) to MscCG and evolved separately from MscCG with four transmembrane helices. Despite the considerable differences between MscCG2 and MscCG in sequence and structure, gene deletion and complementation confirmed that MscCG2 also functioned as an l-glutamate exporter and an osmotic safety valve in C. glutamicum Besides, transcriptional analysis showed that MscCG2 and MscCG genes were transcribed in similar patterns and not induced by l-glutamate-producing conditions. It was also demonstrated that MscCG2-mediated l-glutamate excretion was activated by biotin limitation or penicillin treatment and that constitutive l-glutamate excretion was triggered by a gain-of-function mutation of MscCG2 (A151V). Discovery of MscCG2 will enrich the understanding of bacterial amino acid transport and provide additional targets for exporter engineering. IMPORTANCE The exchange of matter, energy, and information with surroundings is fundamental for cellular metabolism. Therefore, studying transport systems that are essential for these processes is of great significance. Besides, transport systems of bacterial cells are usually related to product excretion as well as product reuptake, making transporter engineering a useful strategy for strain improvement. The significance of our research is in identifying and characterizing a novel l-glutamate exporter from the industrial workhorse Corynebacterium glutamicum , which will enrich the understanding of l-glutamate excretion and provide a new target for studying bacterial amino acid transport and engineering transport reactions. Copyright © 2018 American Society for Microbiology.
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Zhao, Guifang; Liu, Feilin; Lan, Shaowei; Li, Pengdong; Wang, Li; Kou, Junna; Qi, Xiaojuan; Fan, Ruirui; Hao, Deshun; Wu, Chunling; Bai, Tingting; Li, Yulin; Liu, Jin Yu
2015-03-19
Successful stem cell therapy relies on large-scale generation of stem cells and their maintenance in a proliferative multipotent state. This study aimed to establish a three-dimension culture system for large-scale generation of hWJ-MSC and investigated the self-renewal activity, genomic stability and multi-lineage differentiation potential of such hWJ-MSC in enhancing skin wound healing. hWJ-MSC were seeded on gelatin microbeads and cultured in spinning bottles (3D). Cell proliferation, karyotype analysis, surface marker expression, multipotent differentiation (adipogenic, chondrogenic, and osteogenic potentials), and expression of core transcription factors (OCT4, SOX2, NANOG, and C-MYC), as well as their efficacy in accelerating skin wound healing, were investigated and compared with those of hWJ-MSC derived from plate cultres (2D), using in vivo and in vitro experiments. hWJ-MSC attached to and proliferated on gelatin microbeads in 3D cultures reaching a maximum of 1.1-1.30×10(7) cells on 0.5 g of microbeads by days 8-14; in contrast, hWJ-MSC derived from 2D cultures reached a maximum of 6.5 -11.5×10(5) cells per well in a 24-well plate by days 6-10. hWJ-MSC derived by 3D culture incorporated significantly more EdU (P<0.05) and had a significantly higher proliferation index (P<0.05) than those derived from 2D culture. Immunofluorescence staining, real-time PCR, flow cytometry analysis, and multipotency assays showed that hWJ-MSC derived from 3D culture retained MSC surface markers and multipotency potential similar to 2D culture-derived cells. 3D culture-derived hWJ-MSC also retained the expression of core transcription factors at levels comparable to their 2D culture counterparts. Direct injection of hWJ-MSC derived from 3D or 2D cultures into animals exhibited similar efficacy in enhancing skin wound healing. Thus, hWJ-MSC can be expanded markedly in gelatin microbeads, while retaining MSC surface marker expression, multipotent differential potential, and expression of core transcription factors. These cells also efficiently enhanced skin wound healing in vivo, in a manner comparable to that of hWJ-MSC obtained from 2D culture.
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NASA Astrophysics Data System (ADS)
Mustak, S.
2013-09-01
The correction of atmospheric effects is very essential because visible bands of shorter wavelength are highly affected by atmospheric scattering especially of Rayleigh scattering. The objectives of the paper is to find out the haze values present in the all spectral bands and to correct the haze values for urban analysis. In this paper, Improved Dark Object Subtraction method of P. Chavez (1988) is applied for the correction of atmospheric haze in the Resoucesat-1 LISS-4 multispectral satellite image. Dark object Subtraction is a very simple image-based method of atmospheric haze which assumes that there are at least a few pixels within an image which should be black (% reflectance) and such black reflectance termed as dark object which are clear water body and shadows whose DN values zero (0) or Close to zero in the image. Simple Dark Object Subtraction method is a first order atmospheric correction but Improved Dark Object Subtraction method which tends to correct the Haze in terms of atmospheric scattering and path radiance based on the power law of relative scattering effect of atmosphere. The haze values extracted using Simple Dark Object Subtraction method for Green band (Band2), Red band (Band3) and NIR band (band4) are 40, 34 and 18 but the haze values extracted using Improved Dark Object Subtraction method are 40, 18.02 and 11.80 for aforesaid bands. Here it is concluded that the haze values extracted by Improved Dark Object Subtraction method provides more realistic results than Simple Dark Object Subtraction method.
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Miwa, Kenta; Umeda, Takuro; Murata, Taisuke; Wagatsuma, Kei; Miyaji, Noriaki; Terauchi, Takashi; Koizumi, Mitsuru; Sasaki, Masayuki
2016-02-01
Overcorrection of scatter caused by patient motion during whole-body PET/computed tomography (CT) imaging can induce the appearance of photopenic artifacts in the PET images. The present study aimed to quantify the accuracy of scatter limitation correction (SLC) for eliminating photopenic artifacts. This study analyzed photopenic artifacts in (18)F-fluorodeoxyglucose ((18)F-FDG) PET/CT images acquired from 12 patients and from a National Electrical Manufacturers Association phantom with two peripheral plastic bottles that simulated the human body and arms, respectively. The phantom comprised a sphere (diameter, 10 or 37 mm) containing fluorine-18 solutions with target-to-background ratios of 2, 4, and 8. The plastic bottles were moved 10 cm posteriorly between CT and PET acquisitions. All PET data were reconstructed using model-based scatter correction (SC), no scatter correction (NSC), and SLC, and the presence or absence of artifacts on the PET images was visually evaluated. The SC and SLC images were also semiquantitatively evaluated using standardized uptake values (SUVs). Photopenic artifacts were not recognizable in any NSC and SLC image from all 12 patients in the clinical study. The SUVmax of mismatched SLC PET/CT images were almost equal to those of matched SC and SLC PET/CT images. Applying NSC and SLC substantially eliminated the photopenic artifacts on SC PET images in the phantom study. SLC improved the activity concentration of the sphere for all target-to-background ratios. The highest %errors of the 10 and 37-mm spheres were 93.3 and 58.3%, respectively, for mismatched SC, and 73.2 and 22.0%, respectively, for mismatched SLC. Photopenic artifacts caused by SC error induced by CT and PET image misalignment were corrected using SLC, indicating that this method is useful and practical for clinical qualitative and quantitative PET/CT assessment.
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Charif, N; Li, Y Y; Targa, L; Zhang, L; Ye, J S; Li, Y P; Stoltz, J F; Han, H Z; de Isla, N
2017-01-01
With their proliferation, differentiation into specific cell types, and secretion properties, mesenchymal stromal/stem cells (MSC) are very interesting tools to be used in regenerative medicine. Bone marrow (BM) was the first MSC source characterized. In the frame of autologous MSC therapy, it is important to detect donor's parameters affecting MSC potency. Age of the donors appears as one parameter that could greatly affect MSC properties. Moreover, in vitro cell expansion is needed to obtain the number of cells necessary for clinical developments. It will lead to in vitro cell aging that could modify cell properties. This review recapitulates several studies evaluating the effect of in vitro and in vivo MSC aging on cell properties.
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Li, Wen-xia; Li, Feng; Zhao, Guo-liang; Tang, Shi-jun; Liu, Xiao-ying
2014-12-01
A series of 376 cotton-polyester (PET) blend fabrics were studied by a portable near-infrared (NIR) spectrometer. A NIR semi-quantitative-qualitative calibration model was established by Partial Least Squares (PLS) method combined with qualitative identification coefficient. In this process, PLS method in a quantitative analysis was used as a correction method, and the qualitative identification coefficient was set by the content of cotton and polyester in blend fabrics. Cotton-polyester blend fabrics were identified qualitatively by the model and their relative contents were obtained quantitatively, the model can be used for semi-quantitative identification analysis. In the course of establishing the model, the noise and baseline drift of the spectra were eliminated by Savitzky-Golay(S-G) derivative. The influence of waveband selection and different pre-processing method was also studied in the qualitative calibration model. The major absorption bands of 100% cotton samples were in the 1400~1600 nm region, and the one for 100% polyester were around 1600~1800 nm, the absorption intensity was enhancing with the content increasing of cotton or polyester. Therefore, the cotton-polyester's major absorption region was selected as the base waveband, the optimal waveband (1100~2500 nm) was found by expanding the waveband in two directions (the correlation coefficient was 0.6, and wave-point number was 934). The validation samples were predicted by the calibration model, the results showed that the model evaluation parameters was optimum in the 1100~2500 nm region, and the combination of S-G derivative, multiplicative scatter correction (MSC) and mean centering was used as the pre-processing method. RC (relational coefficient of calibration) value was 0.978, RP (relational coefficient of prediction) value was 0.940, SEC (standard error of calibration) value was 1.264, SEP (standard error of prediction) value was 1.590, and the sample's recognition accuracy was up to 93.4%. It showed that the cotton-polyester blend fabrics could be predicted by the semi-quantitative-qualitative calibration model.
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Corrections for the geometric distortion of the tube detectors on SANS instruments at ORNL
He, Lilin; Do, Changwoo; Qian, Shuo; ...
2014-11-25
Small-angle neutron scattering instruments at the Oak Ridge National Laboratory's High Flux Isotope Reactor were upgraded in area detectors from the large, single volume crossed-wire detectors originally installed to staggered arrays of linear position-sensitive detectors (LPSDs). The specific geometry of the LPSD array requires that approaches to data reduction traditionally employed be modified. Here, two methods for correcting the geometric distortion produced by the LPSD array are presented and compared. The first method applies a correction derived from a detector sensitivity measurement performed using the same configuration as the samples are measured. In the second method, a solid angle correctionmore » is derived that can be applied to data collected in any instrument configuration during the data reduction process in conjunction with a detector sensitivity measurement collected at a sufficiently long camera length where the geometric distortions are negligible. Furthermore, both methods produce consistent results and yield a maximum deviation of corrected data from isotropic scattering samples of less than 5% for scattering angles up to a maximum of 35°. The results are broadly applicable to any SANS instrument employing LPSD array detectors, which will be increasingly common as instruments having higher incident flux are constructed at various neutron scattering facilities around the world.« less
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Carrade, Danielle D; Owens, Sean D; Galuppo, Larry D; Vidal, Martin A; Ferraro, Gregory L; Librach, Fred; Buerchler, Sabine; Friedman, Michael S; Walker, Naomi J; Borjesson, Dori L
2011-04-01
The development of an allogeneic mesenchymal stem cell (MSC) product to treat equine disorders would be useful; however, there are limited in vivo safety data for horses. We hypothesized that the injection of self (autologous) and non-self (related allogeneic or allogeneic) MSC would not elicit significant alterations in physical examination, gait or synovial fluid parameters when injected into the joints of healthy horses. Sixteen healthy horses were used in this study. Group 1 consisted of foals (n = 6), group 2 consisted of their dams (n = 5) and group 3 consisted of half-siblings (n = 5) to group 1 foals. Prior to injection, MSC were phenotyped. Placentally derived MSC were injected into contralateral joints and MSC diluent was injected into a separate joint (control). An examination, including lameness evaluation and synovial fluid analysis, was performed at 0, 24, 48 and 72 h post-injection. MSC were major histocompatibility complex (MHC) I positive, MHC II negative and CD86 negative. Injection of allogeneic MSC did not elicit a systemic response. Local responses such as joint swelling or lameness were minimal and variable. Intra-articular MSC injection elicited marked inflammation within the synovial fluid (as measured by nucleated cell count, neutrophil number and total protein concentration). However, there were no significant differences between the degree and type of inflammation elicited by self and non-self-MSC. The healthy equine joint responds similarly to a single intra-articular injection of autologous and allogeneic MSC. This pre-clinical safety study is an important first step in the development of equine allogeneic stem cell therapies.
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Lin, Mei-Na; Shang, De-Shu; Sun, Wei; Li, Bo; Xu, Xin; Fang, Wen-Gang; Zhao, Wei-Dong; Cao, Liu; Chen, Yu-Hua
2013-06-04
Bone marrow-derived mesenchymal stem cells (MSC) represent an important and easily available source of stem cells for potential therapeutic use in neurological diseases. The entry of circulating cells into the central nervous system by intravenous administration requires, firstly, the passage of the cells across the blood-brain barrier (BBB). However, little is known of the details of MSC transmigration across the BBB. In the present study, we employed an in vitro BBB model constructed using a human brain microvascular endothelial cell monolayer to study the mechanism underlying MSC transendothelial migration. Transmigration assays, transendothelial electrical resistance (TEER) and horseradish peroxidase (HRP) flux assays showed that MSC could transmigrate through human brain microvascular endothelial cell monolayers by a paracellular pathway. Cell fractionation and immunofluorescence assays confirmed the disruption of tight junctions. Inhibition assays showed that a Rho-kinase (ROCK) inhibitor (Y27632) effectively promoted MSC transendothelial migration; conversely, a PI3K inhibitor (LY294002) blocked MSC transendothelial migration. Interestingly, adenovirus-mediated interference with ROCK in MSC significantly increased MSC transendothelial migration, and overexpression of a PI3K dominant negative mutant in MSC cells could block transendothelial migration. Our findings provide clear evidence that the PI3K and ROCK pathways are involved in MSC migration through human brain microvascular endothelial cell monolayers. The information yielded by this study may be helpful in constructing gene-modified mesenchymal stem cells that are able to penetrate the BBB effectively for cell therapy. Copyright © 2013 Elsevier B.V. All rights reserved.
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Transduction of Wnt11 promotes mesenchymal stem cell transdifferentiation into cardiac phenotypes.
He, Zhisong; Li, Hongxia; Zuo, Shi; Pasha, Zeeshan; Wang, Yigang; Yang, Yueting; Jiang, Wenping; Ashraf, Muhammad; Xu, Meifeng
2011-10-01
Transplantation of mesenchymal stem cells (MSCs) has emerged as a potential treatment for ischemic heart repair. Previous studies have suggested that Wnt11 plays a critical role in cardiac specification and morphogenesis. In this study, we examined whether transduction of Wnt11 directly increases MSC differentiation into cardiac phenotypes. MSCs harvested from rat bone marrow were transduced with both Wnt11 and green fluorescent protein (GFP) (MSC(Wnt11)) using the murine stem cell virus (pMSCV) retroviral expression system; control cells were only GFP-transfected (MSC(Null)). Compared with control cells, MSC(Wnt11) was shown to have higher expression of Wnt11 by immunofluorescence, real-time polymerase chain reaction, and western blotting. MSC(Wnt11) shows a higher expression of cardiac-specific genes, including GATA-4, brain natriuretic peptide (BNP), islet-1, and α-actinin, after being cultured with cardiomyocytes (CMs) isolated from ventricles of neonatal (1-3 day) SD rats. Some MSC(Wnt11) were positive for α-actinin when MSCs were cocultured with native CMs for 7 days. Electron microscopy further confirmed the appearance of sarcomeres in MSC(Wnt11). Connexin 43 was found between GFP-positive MSCs and neonatal rat CMs labeled with red fluorescent probe PKH26. The transdifferentiation rate was significantly higher in MSC(Wnt11) than in MSC(Null), as assessed by flow cytometry. Functional studies indicated that the differentiation of MSC(Wnt11) was diminished by knockdown of GATA-4 with GATA-4-siRNA. Transduction of Wnt11 into MSCs increases their differentiation into CMs by upregulating GATA-4.
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β1 Integrins Mediate Attachment of Mesenchymal Stem Cells to Cartilage Lesions
Zwolanek, Daniela; Flicker, Magdalena; Kirstätter, Elisabeth; Zaucke, Frank; van Osch, Gerjo J.V.M.; Erben, Reinhold G.
2015-01-01
Abstract Mesenchymal stem cells (MSC) may have great potential for cell-based therapies of osteoarthritis. However, after injection in the joint, only few cells adhere to defective articular cartilage and contribute to cartilage regeneration. Little is known about the molecular mechanisms of MSC attachment to defective articular cartilage. Here, we developed an ex vivo attachment system, using rat osteochondral explants with artificially created full-thickness cartilage defects in combination with genetically labeled MSC isolated from bone marrow of human placental alkaline phosphatase transgenic rats. Binding of MSC to full-thickness cartilage lesions was improved by serum, but not hyaluronic acid, and was dependent on the presence of divalent cations. Additional in vitro tests showed that rat MSC attach, in a divalent cation-dependent manner, to collagen I, collagen II, and fibronectin, but not to collagen XXII or cartilage oligomeric matrix protein (COMP). RGD peptides partially blocked the adhesion of MSC to fibronectin in vitro and to cartilage lesions ex vivo. Furthermore, the attachment of MSC to collagen I and II in vitro and to cartilage lesions ex vivo was almost completely abolished in the presence of a β1 integrin blocking antibody. In conclusion, our data suggest that attachment of MSC to ex vivo full-thickness cartilage lesions is almost entirely β1 integrin-mediated, whereby both RGD- and collagen-binding integrins are involved. These findings suggest a key role of integrins during MSC attachment to defective cartilage and may pave the way for improved MSC-based therapies in the future. PMID:26309781
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Kay, Alasdair G; Long, Grace; Tyler, George; Stefan, Andrei; Broadfoot, Stephen J; Piccinini, Anna M; Middleton, Jim; Kehoe, Oksana
2017-12-21
We evaluated the therapeutic potential of mesenchymal stem cell-conditioned medium (CM-MSC) as an alternative to cell therapy in an antigen-induced model of arthritis (AIA). Disease severity and cartilage loss were evaluated by histopathological analysis of arthritic knee joints and immunostaining of aggrecan neoepitopes. Cell proliferation was assessed for activated and naïve CD4+ T cells from healthy mice following culture with CM-MSC or co-culture with MSCs. T cell polarization was analysed in CD4+ T cells isolated from spleens and lymph nodes of arthritic mice treated with CM-MSC or MSCs. CM-MSC treatment significantly reduced knee-joint swelling, histopathological signs of AIA, cartilage loss and suppressed TNFα induction. Proliferation of CD4+ cells from spleens of healthy mice was not affected by CM-MSC but reduced when cells were co-cultured with MSCs. In the presence of CM-MSC or MSCs, increases in IL-10 concentration were observed in culture medium. Finally, CD4+ T cells from arthritic mice treated with CM-MSC showed increases in FOXP3 and IL-4 expression and positively affected the Treg:Th17 balance in the tissue. CM-MSC treatment reduces cartilage damage and suppresses immune responses by reducing aggrecan cleavage, enhancing Treg function and adjusting the Treg:Th17 ratio. CM-MSC may provide an effective cell-free therapy for inflammatory arthritis.
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Zhang, Bin; Wu, Xiaodan; Zhang, Xu; Sun, Yaoxiang; Yan, Yongmin; Shi, Hui; Zhu, Yanhua; Wu, Lijun; Pan, Zhaoji; Zhu, Wei
2015-01-01
Human umbilical cord mesenchymal stem cells (hucMSCs) and their exosomes have been considered as potential therapeutic tools for tissue regeneration; however, the underlying mechanisms are still not well understood. In this study, we isolated and characterized the exosomes from hucMSCs (hucMSC-Ex) and demonstrated that hucMSC-Ex promoted the proliferation, migration, and tube formation of endothelial cells in a dose-dependent manner. Furthermore, we demonstrated that hucMSC-Ex promoted wound healing and angiogenesis in vivo by using a rat skin burn model. We discovered that hucMSC-Ex promoted β-catenin nuclear translocation and induced the increased expression of proliferating cell nuclear antigen, cyclin D3, N-cadherin, and β-catenin and the decreased expression of E-cadherin. The activation of Wnt/β-catenin is critical in the induction of angiogenesis by hucMSC-Ex, which could be reversed by β-catenin inhibitor ICG-001. Wnt4 was delivered by hucMSC-Ex, and the knockdown of Wnt4 in hucMSC-Ex abrogated β-catenin nuclear translocation in endothelial cells. The in vivo proangiogenic effects were also inhibited by interference of Wnt4 expression in hucMSC-Ex. Taken together, these results suggest that hucMSC-Ex-mediated Wnt4 induces β-catenin activation in endothelial cells and exerts proangiogenic effects, which could be an important mechanism for cutaneous wound healing. PMID:25824139
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Extending 3D Near-Cloud Corrections from Shorter to Longer Wavelengths
NASA Technical Reports Server (NTRS)
Marshak, Alexander; Evans, K. Frank; Varnai, Tamas; Guoyong, Wen
2014-01-01
Satellite observations have shown a positive correlation between cloud amount and aerosol optical thickness (AOT) that can be explained by the humidification of aerosols near clouds, and/or by cloud contamination by sub-pixel size clouds and the cloud adjacency effect. The last effect may substantially increase reflected radiation in cloud-free columns, leading to overestimates in the retrieved AOT. For clear-sky areas near boundary layer clouds the main contribution to the enhancement of clear sky reflectance at shorter wavelengths comes from the radiation scattered into clear areas by clouds and then scattered to the sensor by air molecules. Because of the wavelength dependence of air molecule scattering, this process leads to a larger reflectance increase at shorter wavelengths, and can be corrected using a simple two-layer model. However, correcting only for molecular scattering skews spectral properties of the retrieved AOT. Kassianov and Ovtchinnikov proposed a technique that uses spectral reflectance ratios to retrieve AOT in the vicinity of clouds; they assumed that the cloud adjacency effect influences the spectral ratio between reflectances at two wavelengths less than it influences the reflectances themselves. This paper combines the two approaches: It assumes that the 3D correction for the shortest wavelength is known with some uncertainties, and then it estimates the 3D correction for longer wavelengths using a modified ratio method. The new approach is tested with 3D radiances simulated for 26 cumulus fields from Large-Eddy Simulations, supplemented with 40 aerosol profiles. The results showed that (i) for a variety of cumulus cloud scenes and aerosol profiles over ocean the 3D correction due to cloud adjacency effect can be extended from shorter to longer wavelengths and (ii) the 3D corrections for longer wavelengths are not very sensitive to unbiased random uncertainties in the 3D corrections at shorter wavelengths.
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Anizan, Nadège; Carlier, Thomas; Hindorf, Cecilia; Barbet, Jacques; Bardiès, Manuel
2012-02-13
Noninvasive multimodality imaging is essential for preclinical evaluation of the biodistribution and pharmacokinetics of radionuclide therapy and for monitoring tumor response. Imaging with nonstandard positron-emission tomography [PET] isotopes such as 124I is promising in that context but requires accurate activity quantification. The decay scheme of 124I implies an optimization of both acquisition settings and correction processing. The PET scanner investigated in this study was the Inveon PET/CT system dedicated to small animal imaging. The noise equivalent count rate [NECR], the scatter fraction [SF], and the gamma-prompt fraction [GF] were used to determine the best acquisition parameters for mouse- and rat-sized phantoms filled with 124I. An image-quality phantom as specified by the National Electrical Manufacturers Association NU 4-2008 protocol was acquired and reconstructed with two-dimensional filtered back projection, 2D ordered-subset expectation maximization [2DOSEM], and 3DOSEM with maximum a posteriori [3DOSEM/MAP] algorithms, with and without attenuation correction, scatter correction, and gamma-prompt correction (weighted uniform distribution subtraction). Optimal energy windows were established for the rat phantom (390 to 550 keV) and the mouse phantom (400 to 590 keV) by combining the NECR, SF, and GF results. The coincidence time window had no significant impact regarding the NECR curve variation. Activity concentration of 124I measured in the uniform region of an image-quality phantom was underestimated by 9.9% for the 3DOSEM/MAP algorithm with attenuation and scatter corrections, and by 23% with the gamma-prompt correction. Attenuation, scatter, and gamma-prompt corrections decreased the residual signal in the cold insert. The optimal energy windows were chosen with the NECR, SF, and GF evaluation. Nevertheless, an image quality and an activity quantification assessment were required to establish the most suitable reconstruction algorithm and corrections for 124I small animal imaging.
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Improved determination of particulate absorption from combined filter pad and PSICAM measurements.
Lefering, Ina; Röttgers, Rüdiger; Weeks, Rebecca; Connor, Derek; Utschig, Christian; Heymann, Kerstin; McKee, David
2016-10-31
Filter pad light absorption measurements are subject to two major sources of experimental uncertainty: the so-called pathlength amplification factor, β, and scattering offsets, o, for which previous null-correction approaches are limited by recent observations of non-zero absorption in the near infrared (NIR). A new filter pad absorption correction method is presented here which uses linear regression against point-source integrating cavity absorption meter (PSICAM) absorption data to simultaneously resolve both β and the scattering offset. The PSICAM has previously been shown to provide accurate absorption data, even in highly scattering waters. Comparisons of PSICAM and filter pad particulate absorption data reveal linear relationships that vary on a sample by sample basis. This regression approach provides significantly improved agreement with PSICAM data (3.2% RMS%E) than previously published filter pad absorption corrections. Results show that direct transmittance (T-method) filter pad absorption measurements perform effectively at the same level as more complex geometrical configurations based on integrating cavity measurements (IS-method and QFT-ICAM) because the linear regression correction compensates for the sensitivity to scattering errors in the T-method. This approach produces accurate filter pad particulate absorption data for wavelengths in the blue/UV and in the NIR where sensitivity issues with PSICAM measurements limit performance. The combination of the filter pad absorption and PSICAM is therefore recommended for generating full spectral, best quality particulate absorption data as it enables correction of multiple errors sources across both measurements.
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Coastal Zone Color Scanner atmospheric correction algorithm - Multiple scattering effects
NASA Technical Reports Server (NTRS)
Gordon, Howard R.; Castano, Diego J.
1987-01-01
Errors due to multiple scattering which are expected to be encountered in application of the current Coastal Zone Color Scanner (CZCS) atmospheric correction algorithm are analyzed. The analysis is based on radiative transfer computations in model atmospheres, in which the aerosols and molecules are distributed vertically in an exponential manner, with most of the aerosol scattering located below the molecular scattering. A unique feature of the analysis is that it is carried out in scan coordinates rather than typical earth-sun coordinates, making it possible to determine the errors along typical CZCS scan lines. Information provided by the analysis makes it possible to judge the efficacy of the current algorithm with the current sensor and to estimate the impact of the algorithm-induced errors on a variety of applications.
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Performance-enhanced mesenchymal stem cells via intracellular delivery of steroids
NASA Astrophysics Data System (ADS)
Ankrum, James A.; Dastidar, Riddhi G.; Ong, Joon Faii; Levy, Oren; Karp, Jeffrey M.
2014-04-01
Inadequate immunomodulatory potency of mesenchymal stem cells (MSC) may limit their therapeutic efficacy. We report glucocorticoid steroids augment MSC expression and activity of indoleamine-2,3-dioxygenase (IDO), a primary mediator of MSC immunomodulatory function. This effect depends on signaling through the glucocorticoid receptor and is mediated through up-regulation of FOXO3. Treatment of MSCs with glucocorticoids, budesonide or dexamethasone, enhanced IDO expression following IFN-γ stimulation in multiple donors and was able to restore IDO expression in over-passaged MSCs. As IDO enhancement was most notable when cells were continuously exposed to budesonide, we engineered MSC with budesonide loaded PLGA microparticles. MSC efficiently internalized budesonide microparticles and exhibited 4-fold enhanced IDO activity compared to budesonide preconditioned and naïve MSC, resulting in a 2-fold improvement in suppression of stimulated peripheral blood mononuclear cells in an IDO-dependent manner. Thus, the augmentation of MSC immune modulation may abrogate challenges associated with inadequate potency and enhance their therapeutic efficacy.
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Performance-enhanced mesenchymal stem cells via intracellular delivery of steroids
Ankrum, James A.; Dastidar, Riddhi G.; Ong, Joon Faii; Levy, Oren; Karp, Jeffrey M.
2014-01-01
Inadequate immunomodulatory potency of mesenchymal stem cells (MSC) may limit their therapeutic efficacy. We report glucocorticoid steroids augment MSC expression and activity of indoleamine-2,3-dioxygenase (IDO), a primary mediator of MSC immunomodulatory function. This effect depends on signaling through the glucocorticoid receptor and is mediated through up-regulation of FOXO3. Treatment of MSCs with glucocorticoids, budesonide or dexamethasone, enhanced IDO expression following IFN-γ stimulation in multiple donors and was able to restore IDO expression in over-passaged MSCs. As IDO enhancement was most notable when cells were continuously exposed to budesonide, we engineered MSC with budesonide loaded PLGA microparticles. MSC efficiently internalized budesonide microparticles and exhibited 4-fold enhanced IDO activity compared to budesonide preconditioned and naïve MSC, resulting in a 2-fold improvement in suppression of stimulated peripheral blood mononuclear cells in an IDO-dependent manner. Thus, the augmentation of MSC immune modulation may abrogate challenges associated with inadequate potency and enhance their therapeutic efficacy. PMID:24717973
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Generation of immunosuppressive mesenchymal stem cells in allogeneic human serum.
Le Blanc, Katarina; Samuelsson, Håkan; Lönnies, Lena; Sundin, Mikael; Ringdén, Olle
2007-10-27
Mesenchymal stem cells (MSC) may be used to treat acute graft-versus-host disease and for tissue repair. In vitro expansion of MSC has been achieved in the presence of fetal calf serum (FCS). For safety and regulatory reasons, we explored if FCS could be replaced by human blood group AB serum. Proliferation and fold increase of MSC was higher in the presence of AB-serum, compared to FCS. Similar to cells generated in FCS media, MSC from AB-serum media were more than 95% positive for CD90, CD105 and human leukocyte antigen (HLA) class I, and negative for hematopoietic and endothelial markers CD14, CD31, CD34, CD45, and CD80. HLA class II expression was higher in MSC generated in AB-serum, but decreased with higher passage numbers. MSC generated in AB-serum suppressed lymphocyte proliferation in mixed lymphocyte cultures and after stimulation with phytohemagglutinin. MSC expanded in AB-serum and FCS have similar in vitro properties.
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Chavez, P.S.
1988-01-01
Digital analysis of remotely sensed data has become an important component of many earth-science studies. These data are often processed through a set of preprocessing or "clean-up" routines that includes a correction for atmospheric scattering, often called haze. Various methods to correct or remove the additive haze component have been developed, including the widely used dark-object subtraction technique. A problem with most of these methods is that the haze values for each spectral band are selected independently. This can create problems because atmospheric scattering is highly wavelength-dependent in the visible part of the electromagnetic spectrum and the scattering values are correlated with each other. Therefore, multispectral data such as from the Landsat Thematic Mapper and Multispectral Scanner must be corrected with haze values that are spectral band dependent. An improved dark-object subtraction technique is demonstrated that allows the user to select a relative atmospheric scattering model to predict the haze values for all the spectral bands from a selected starting band haze value. The improved method normalizes the predicted haze values for the different gain and offset parameters used by the imaging system. Examples of haze value differences between the old and improved methods for Thematic Mapper Bands 1, 2, 3, 4, 5, and 7 are 40.0, 13.0, 12.0, 8.0, 5.0, and 2.0 vs. 40.0, 13.2, 8.9, 4.9, 16.7, and 3.3, respectively, using a relative scattering model of a clear atmosphere. In one Landsat multispectral scanner image the haze value differences for Bands 4, 5, 6, and 7 were 30.0, 50.0, 50.0, and 40.0 for the old method vs. 30.0, 34.4, 43.6, and 6.4 for the new method using a relative scattering model of a hazy atmosphere. ?? 1988.
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Kalimuthu, Senthilkumar; Oh, Ji Min; Gangadaran, Prakash; Zhu, Liya; Lee, Ho Won; Jeon, Yong Hyun; Jeong, Shin Young; Lee, Sang-Woo; Lee, Jaetae; Ahn, Byeong-Cheol
2017-01-01
Anaplastic thyroid cancer (ATC) is the most aggressive malignancy of the thyroid, during which undifferentiated tumors arise from the thyroid follicular epithelium. ATC has a very poor prognosis due to its aggressive behavior and poor response to conventional therapies. Gene-directed enzyme/prodrug therapy using genetically engineered mesenchymal stromal cells (MSC) is a promising therapeutic strategy. The doxycycline (DOX)-controlled Tet inducible system is the most widely utilized regulatory system and could be a useful tool for therapeutic gene-based therapies. For example, use a synthetic "tetracycline-on" switch system to control the expression of the therapeutic gene thymidine kinase, which converts prodrugs to active drugs. The aim of this study was to develop therapeutic MSCs, harboring an inducible suicide gene, and to validate therapeutic gene expression using optical molecular imaging of ATC. We designed the Tet-On system using a retroviral vector expressing herpes simplex virus thymidine kinase (HSV1-sr39TK) with dual reporters (eGFP-Fluc2). Mouse bone marrow-derived mesenchymal stromal cells (BM-MSC) were transduced using this system with (MSC-Tet-TK/Fluc2) or without (MSC-TK/Fluc) the Tet-On system. Transduced cells were screened and characterized. Engineered MSCs were co-cultured with ATC (CAL62/Rluc) cells in the presence of the prodrug ganciclovir (GCV) and stimulated with DOX. The efficiency of cell killing monitored by assessing Rluc (CAL62/Rluc) and Fluc (MSC-Tet-TK/Fluc and MSC-TK/Fluc) activities using IVIS imaging. Fluc activity increased in MSC-Tet-TK/Fluc cells in a dose dependent manner following DOX treatment (R2 = 0.95), whereas no signal was observed in untreated cells. eGFP could also be visualized after induction with DOX, and the HSV1-TK protein could be detected by western blotting. In MSC-TK/Fluc cells, the Fluc activity increased with increasing cell number (R2 = 0.98), and eGFP could be visualized by fluorescence microscopy. The Fluc activity and cell viability of MSC-Tet-TK/Fluc and MSC-TK/Fluc cells decreased significantly following GCV treatment. A bystander effect of the therapeutic cells confirmed in co-cultures of CAL62 cells, an anaplastic thyroid cancer cell line, with either MSC-Tet-TK/Fluc cells or MSC-TK/Fluc cells. The Rluc activity in MSC-Tet-TK/Fluc co-cultures, derived from the CAL62/Rluc cells, decreased significantly with GCV treatment of DOX treated cultures, whereas no significant changes were observed in untreated cultures. In addition, the Fluc activity of MSC-Tet-TK/Fluc cells also decreased significantly with DOX treatment whereas no signal was present in untreated cultures. A bystander effect also be demonstrated in co-cultures with MSC-TK/Fluc cells and CAL62/Rluc; both the Rluc activity and the Fluc activity were significantly decreased following GCV treatment. We have successfully developed a Tet-On system of gene-directed enzyme/prodrug delivery using MSCs. We confirmed the therapeutic bystander effect in CAL62/Rluc cells with respect to MSC-Tet-TK/Fluc and MSC-TK/Fluc cells after GCV treatment with and without DOX. Our results confirm the therapeutic efficiency of a suicide gene, with or without the Tet-On system, for ATC therapy. In addition, our findings provide an innovative therapeutic approach for using the Tet-On system to eradicate tumors by simple, repeated administration of MSC-Tet-TK/Fluc cells with DOX and GCV.
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Scattering of Femtosecond Laser Pulses on the Negative Hydrogen Ion
NASA Astrophysics Data System (ADS)
Astapenko, V. A.; Moroz, N. N.
2018-05-01
Elastic scattering of ultrashort laser pulses (USLPs) on the negative hydrogen ion is considered. Results of calculations of the USLP scattering probability are presented and analyzed for pulses of two types: the corrected Gaussian pulse and wavelet pulse without carrier frequency depending on the problem parameters.
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NASA Astrophysics Data System (ADS)
Li, Runze; Peng, Tong; Liang, Yansheng; Yang, Yanlong; Yao, Baoli; Yu, Xianghua; Min, Junwei; Lei, Ming; Yan, Shaohui; Zhang, Chunmin; Ye, Tong
2017-10-01
Focusing and imaging through scattering media has been proved possible with high resolution wavefront shaping. A completely scrambled scattering field can be corrected by applying a correction phase mask on a phase only spatial light modulator (SLM) and thereby the focusing quality can be improved. The correction phase is often found by global searching algorithms, among which Genetic Algorithm (GA) stands out for its parallel optimization process and high performance in noisy environment. However, the convergence of GA slows down gradually with the progression of optimization, causing the improvement factor of optimization to reach a plateau eventually. In this report, we propose an interleaved segment correction (ISC) method that can significantly boost the improvement factor with the same number of iterations comparing with the conventional all segment correction method. In the ISC method, all the phase segments are divided into a number of interleaved groups; GA optimization procedures are performed individually and sequentially among each group of segments. The final correction phase mask is formed by applying correction phases of all interleaved groups together on the SLM. The ISC method has been proved significantly useful in practice because of its ability to achieve better improvement factors when noise is present in the system. We have also demonstrated that the imaging quality is improved as better correction phases are found and applied on the SLM. Additionally, the ISC method lowers the demand of dynamic ranges of detection devices. The proposed method holds potential in applications, such as high-resolution imaging in deep tissue.
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Berger, Edmond L; Gao, Jun; Li, Chong Sheng; Liu, Ze Long; Zhu, Hua Xing
2016-05-27
We present a fully differential next-to-next-to-leading order calculation of charm-quark production in charged-current deep-inelastic scattering, with full charm-quark mass dependence. The next-to-next-to-leading order corrections in perturbative quantum chromodynamics are found to be comparable in size to the next-to-leading order corrections in certain kinematic regions. We compare our predictions with data on dimuon production in (anti)neutrino scattering from a heavy nucleus. Our results can be used to improve the extraction of the parton distribution function of a strange quark in the nucleon.
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SU-F-T-142: An Analytical Model to Correct the Aperture Scattered Dose in Clinical Proton Beams
DOE Office of Scientific and Technical Information (OSTI.GOV)
Sun, B; Liu, S; Zhang, T
2016-06-15
Purpose: Apertures or collimators are used to laterally shape proton beams in double scattering (DS) delivery and to sharpen the penumbra in pencil beam (PB) delivery. However, aperture-scattered dose is not included in the current dose calculations of treatment planning system (TPS). The purpose of this study is to provide a method to correct the aperture-scattered dose based on an analytical model. Methods: A DS beam with a non-divergent aperture was delivered using a single-room proton machine. Dose profiles were measured with an ion-chamber scanning in water and a 2-D ion chamber matrix with solid-water buildup at various depths. Themore » measured doses were considered as the sum of the non-contaminated dose and the aperture-scattered dose. The non-contaminated dose was calculated by TPS and subtracted from the measured dose. Aperture scattered-dose was modeled as a 1D Gaussian distribution. For 2-D fields, to calculate the scatter-dose from all the edges of aperture, a sum of weighted distance was used in the model based on the distance from calculation point to aperture edge. The gamma index was calculated between the measured and calculated dose with and without scatter correction. Results: For a beam with range of 23 cm and aperture size of 20 cm, the contribution of the scatter horn was ∼8% of the total dose at 4 cm depth and diminished to 0 at 15 cm depth. The amplitude of scatter-dose decreased linearly with the depth increase. The 1D gamma index (2%/2 mm) between the calculated and measured profiles increased from 63% to 98% for 4 cm depth and from 83% to 98% at 13 cm depth. The 2D gamma index (2%/2 mm) at 4 cm depth has improved from 78% to 94%. Conclusion: Using the simple analytical method the discrepancy between the measured and calculated dose has significantly improved.« less
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Marquina, Maribel; Collado, Javier A; Pérez-Cruz, Magdiel; Fernández-Pernas, Pablo; Fafián-Labora, Juan; Blanco, Francisco J; Máñez, Rafael; Arufe, María C; Costa, Cristina
2017-01-01
Xenogeneic chondrocytes and allogeneic mesenchymal stem cells (MSC) are considered a potential source of cells for articular cartilage repair. We here assessed the immune response triggered by xenogeneic chondrocytes when injected intraarticularly, as well as the immunoregulatory effect of allogeneic bone marrow-derived MSC after systemic administration. To this end, a discordant xenotransplantation model was established by injecting three million porcine articular chondrocytes (PAC) into the femorotibial joint of Lewis rats and monitoring the immune response. First, the fate of MSC injected using various routes was monitored in an in vivo imaging system. The biodistribution revealed a dependency on the injection route with MSC injected intravenously (i.v.) succumbing early after 24 h and MSC injected intraperitoneally (i.p.) lasting locally for at least 5 days. Importantly, no migration of MSC to the joint was detected in rats previously injected with PAC. MSC were then administered either i.v. 1 week before PAC injection or i.p. 3 weeks after to assess their immunomodulatory function on humoral and adaptive immune parameters. Anti-PAC IgM and IgG responses were detected in all PAC-injected rats with a peak at week 2 postinjection and reactivity remaining above baseline levels by week 18. IgG2a and IgG2b were the predominant and long-lasting IgG subtypes. By contrast, no anti-MSC antibody response was detected in the cohort injected with MSC only, but infusion of MSC before PAC injection temporarily augmented the anti-PAC antibody response. Consistent with a cellular immune response to PAC in PAC-injected rats, cytokine/chemokine profiling in serum by antibody array revealed a distinct pattern relative to controls characterized by elevation of multiple markers at week 2, as well as increases in proliferation in draining lymph nodes. Notably, systemic administration of allogeneic MSC under the described conditions did not diminish the immune response. IL-2 measurements in cocultures of rat peripheral blood lymphocytes with PAC indicated that PAC injection induced some T-cell hyporesponsiveness that was not enhanced in the cohorts additionally receiving MSC. Thus, PAC injected intraarticularly in Lewis rats induced a cellular and humoral immune response that was not counteracted by the systemic administration of allogeneic MSC under the described conditions.
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Koh, Yong-Gon; Kwon, Oh-Ryong; Kim, Yong-Sang; Choi, Yun-Jin
2014-11-01
This study compared the clinical results and second-look arthroscopic findings of patients undergoing open-wedge high tibial osteotomy (HTO) for varus deformity, with or without mesenchymal stem cell (MSC) therapy. This prospective, comparative observational study was designed to evaluate the effectiveness of MSC therapy. The patients were divided into 2 groups: HTO with platelet-rich plasma (PRP) injection only (n = 23) or HTO in conjunction with MSC therapy and PRP injection (n = 21). Prospective evaluations of both groups were performed using the Lysholm score, Knee Injury and Osteoarthritis Outcome Score (KOOS), and a visual analog scale (VAS) score for pain. Second-look arthroscopy was carried out in all patients at the time of metal removal. The patients in the MSC-PRP group showed significantly greater improvements in the KOOS subscales for pain (PRP only, 74.0 ± 5.7; MSC-PRP, 81.2 ± 6.9; P < .001) and symptoms (PRP only, 75.4 ± 8.5; MSC-PRP, 82.8 ± 7.2; P = .006) relative to the PRP-only group. Although the mean Lysholm score was similarly improved in both groups (PRP only, 80.6 ± 13.5; MSC-PRP, 84.7 ± 16.2; P = .357), the MSC-PRP group showed a significantly greater improvement in the VAS pain score (PRP only, 16.2 ± 4.6; MSC-PRP, 10.2 ± 5.7; P < .001). There were no differences in the preoperative (PRP only, varus 2.8° ± 1.7°; MSC-PRP, varus 3.4° ± 3.0°; P = .719) and postoperative (PRP only, valgus 9.8° ± 2.4°; MSC-PRP, valgus 8.7° ± 2.3°; P = .678) femorotibial angles or weight-bearing lines between the groups. Arthroscopic evaluation, at plate removal, showed that partial or even fibrocartilage coverage was achieved in 50% of the MSC-PRP group patients but in only 10% of the patients in the PRP-only group (P < .001). MSC therapy, in conjunction with HTO, mildly improved cartilage healing and showed good clinical results in some KOOS subscores and the VAS pain score compared with PRP only. Level II, prospective comparative study. Copyright © 2014 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.
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Garikipati, Venkata Naga Srikanth; Jadhav, Sachin; Pal, Lily; Prakash, Prem; Dikshit, Madhu; Nityanand, Soniya
2014-01-01
Mesenchymal stem cells (MSC) have emerged as a potential stem cell type for cardiac regeneration after myocardial infarction (MI). Recently, we isolated and characterized mesenchymal stem cells derived from rat fetal heart (fC-MSC), which exhibited potential to differentiate into cardiomyocytes, endothelial cells and smooth muscle cells in vitro. In the present study, we investigated the therapeutic efficacy of intravenously injected fC-MSC in a rat model of MI using multi-pinhole gated SPECT-CT system. fC-MSC were isolated from the hearts of Sprague Dawley (SD) rat fetuses at gestation day 16 and expanded ex vivo. One week after induction of MI, 2×106 fC-MSC labeled with PKH26 dye (n = 6) or saline alone (n = 6) were injected through the tail vein of the rats. Initial in vivo tracking of 99mTc-labeled fC-MSC revealed a focal uptake of cells in the anterior mid-ventricular region of the heart. At 4 weeks of fC-MSC administration, the cells labeled with PKH26 were located in abundance in infarct/peri-infarct region and the fC-MSC treated hearts showed a significant increase in left ventricular ejection fraction and a significant decrease in the end diastolic volume, end systolic volume and left ventricular myo-mass in comparison to the saline treated group. In addition, fC-MSC treated hearts had a significantly better myocardial perfusion and attenuation in the infarct size, in comparison to the saline treated hearts. The engrafted PKH26-fC-MSC expressed cardiac troponin T, endothelial CD31 and smooth muscle sm-MHC, suggesting their differentiation into all major cells of cardiovascular lineage. The fC-MSC treated hearts demonstrated an up-regulation of cardio-protective growth factors, anti-fibrotic and anti-apoptotic molecules, highlighting that the observed left ventricular functional recovery may be due to secretion of paracrine factors by fC-MSC. Taken together, our results suggest that fC-MSC therapy may be a new therapeutic strategy for MI and multi-pinhole gated SPECT-CT system may be a useful tool to evaluate cardiac perfusion, function and cell tracking after stem cell therapy in acute myocardial injury setting. PMID:24971627
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Marquina, Maribel; Collado, Javier A.; Pérez-Cruz, Magdiel; Fernández-Pernas, Pablo; Fafián-Labora, Juan; Blanco, Francisco J.; Máñez, Rafael; Arufe, María C.; Costa, Cristina
2017-01-01
Xenogeneic chondrocytes and allogeneic mesenchymal stem cells (MSC) are considered a potential source of cells for articular cartilage repair. We here assessed the immune response triggered by xenogeneic chondrocytes when injected intraarticularly, as well as the immunoregulatory effect of allogeneic bone marrow-derived MSC after systemic administration. To this end, a discordant xenotransplantation model was established by injecting three million porcine articular chondrocytes (PAC) into the femorotibial joint of Lewis rats and monitoring the immune response. First, the fate of MSC injected using various routes was monitored in an in vivo imaging system. The biodistribution revealed a dependency on the injection route with MSC injected intravenously (i.v.) succumbing early after 24 h and MSC injected intraperitoneally (i.p.) lasting locally for at least 5 days. Importantly, no migration of MSC to the joint was detected in rats previously injected with PAC. MSC were then administered either i.v. 1 week before PAC injection or i.p. 3 weeks after to assess their immunomodulatory function on humoral and adaptive immune parameters. Anti-PAC IgM and IgG responses were detected in all PAC-injected rats with a peak at week 2 postinjection and reactivity remaining above baseline levels by week 18. IgG2a and IgG2b were the predominant and long-lasting IgG subtypes. By contrast, no anti-MSC antibody response was detected in the cohort injected with MSC only, but infusion of MSC before PAC injection temporarily augmented the anti-PAC antibody response. Consistent with a cellular immune response to PAC in PAC-injected rats, cytokine/chemokine profiling in serum by antibody array revealed a distinct pattern relative to controls characterized by elevation of multiple markers at week 2, as well as increases in proliferation in draining lymph nodes. Notably, systemic administration of allogeneic MSC under the described conditions did not diminish the immune response. IL-2 measurements in cocultures of rat peripheral blood lymphocytes with PAC indicated that PAC injection induced some T-cell hyporesponsiveness that was not enhanced in the cohorts additionally receiving MSC. Thus, PAC injected intraarticularly in Lewis rats induced a cellular and humoral immune response that was not counteracted by the systemic administration of allogeneic MSC under the described conditions. PMID:29163532
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Lee, Ho; Xing Lei; Lee, Rena
2012-05-15
Purpose: X-ray scatter incurred to detectors degrades the quality of cone-beam computed tomography (CBCT) and represents a problem in volumetric image guided and adaptive radiation therapy. Several methods using a beam blocker for the estimation and subtraction of scatter have been proposed. However, due to missing information resulting from the obstruction of the blocker, such methods require dual scanning or dynamically moving blocker to obtain a complete volumetric image. Here, we propose a half beam blocker-based approach, in conjunction with a total variation (TV) regularized Feldkamp-Davis-Kress (FDK) algorithm, to correct scatter-induced artifacts by simultaneously acquiring image and scatter information frommore » a single-rotation CBCT scan. Methods: A half beam blocker, comprising lead strips, is used to simultaneously acquire image data on one side of the projection data and scatter data on the other half side. One-dimensional cubic B-Spline interpolation/extrapolation is applied to derive patient specific scatter information by using the scatter distributions on strips. The estimated scatter is subtracted from the projection image acquired at the opposite view. With scatter-corrected projections where this subtraction is completed, the FDK algorithm based on a cosine weighting function is performed to reconstruct CBCT volume. To suppress the noise in the reconstructed CBCT images produced by geometric errors between two opposed projections and interpolated scatter information, total variation regularization is applied by a minimization using a steepest gradient descent optimization method. The experimental studies using Catphan504 and anthropomorphic phantoms were carried out to evaluate the performance of the proposed scheme. Results: The scatter-induced shading artifacts were markedly suppressed in CBCT using the proposed scheme. Compared with CBCT without a blocker, the nonuniformity value was reduced from 39.3% to 3.1%. The root mean square error relative to values inside the regions of interest selected from a benchmark scatter free image was reduced from 50 to 11.3. The TV regularization also led to a better contrast-to-noise ratio. Conclusions: An asymmetric half beam blocker-based FDK acquisition and reconstruction technique has been established. The proposed scheme enables simultaneous detection of patient specific scatter and complete volumetric CBCT reconstruction without additional requirements such as prior images, dual scans, or moving strips.« less
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Kashiwagi, Toru; Yutani, Kenji; Fukuchi, Minoru; Naruse, Hitoshi; Iwasaki, Tadaaki; Yokozuka, Koichi; Inoue, Shinichi; Kondo, Shoji
2002-06-01
Improvements in image quality and quantitation measurement, and the addition of detailed anatomical structures are important topics for single-photon emission tomography (SPECT). The goal of this study was to develop a practical system enabling both nonuniform attenuation correction and image fusion of SPECT images by means of high-performance X-ray computed tomography (CT). A SPECT system and a helical X-ray CT system were placed next to each other and linked with Ethernet. To avoid positional differences between the SPECT and X-ray CT studies, identical flat patient tables were used for both scans; body distortion was minimized with laser beams from the upper and lateral directions to detect the position of the skin surface. For the raw projection data of SPECT, a scatter correction was performed with the triple energy window method. Image fusion of the X-ray CT and SPECT images was performed automatically by auto-registration of fiducial markers attached to the skin surface. After registration of the X-ray CT and SPECT images, an X-ray CT-derived attenuation map was created with the calibration curve for 99mTc. The SPECT images were then reconstructed with scatter and attenuation correction by means of a maximum likelihood expectation maximization algorithm. This system was evaluated in torso and cylindlical phantoms and in 4 patients referred for myocardial SPECT imaging with Tc-99m tetrofosmin. In the torso phantom study, the SPECT and X-ray CT images overlapped exactly on the computer display. After scatter and attenuation correction, the artifactual activity reduction in the inferior wall of the myocardium improved. Conversely, the incresed activity around the torso surface and the lungs was reduced. In the abdomen, the liver activity, which was originally uniform, had recovered after scatter and attenuation correction processing. The clinical study also showed good overlapping of cardiac and skin surface outlines on the fused SPECT and X-ray CT images. The effectiveness of the scatter and attenuation correction process was similar to that observed in the phantom study. Because the total time required for computer processing was less than 10 minutes, this method of attenuation correction and image fusion for SPECT images is expected to become popular in clinical practice.
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Russell, Katie C.; Tucker, H. Alan; Bunnell, Bruce A.; Andreeff, Michael; Schober, Wendy; Gaynor, Andrew S.; Strickler, Karen L.; Lin, Shuwen; Lacey, Michelle R.
2013-01-01
Cellular heterogeneity of mesenchymal stem cells (MSCs) impedes their use in regenerative medicine. The objective of this research is to identify potential biomarkers for the enrichment of progenitors from heterogeneous MSC cultures. To this end, the present study examines variation in expression of neuron-glial antigen 2 (NG2) and melanoma cell adhesion molecule (CD146) on the surface of MSCs derived from human bone marrow in response to culture conditions and among cell populations. Multipotent cells isolated from heterogeneous MSC cultures exhibit a greater than three-fold increase in surface expression for NG2 and greater than two-fold increase for CD146 as compared with parental and lineage-committed MSCs. For both antigens, surface expression is downregulated by greater than or equal to six-fold when MSCs become confluent. During serial passage, maximum surface expression of NG2 and CD146 is associated with minimum doubling time. Upregulation of NG2 and CD146 during loss of adipogenic potential at early passage suggests some limits to their utility as potency markers. A potential relationship between proliferation and antigen expression was explored by sorting heterogeneous MSCs into rapidly and slowly dividing groups. Fluorescence-activated cell sorting revealed that rapidly dividing MSCs display lower scatter and 50% higher NG2 surface expression than slowly dividing cells, but CD146 expression is comparable in both groups. Heterogeneous MSCs were sorted based on scatter properties and surface expression of NG2 and CD146 into high (HI) and low (LO) groups. ScLONG2HI and ScLONG2HICD146HI MSCs have the highest proliferative potential of the sorted groups, with colony-forming efficiencies that are 1.5–2.2 times the value for the parental controls. The ScLO gate enriches for rapidly dividing cells. Addition of the NG2HI gate increases cell survival to 1.5 times the parental control. Further addition of the CD146HI gate does not significantly improve cell division or survival. The combination of low scatter and high NG2 surface expression is a promising selection criterion to enrich a proliferative phenotype from heterogeneous MSCs during ex vivo expansion, with potentially numerous applications. PMID:23611563
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NASA Technical Reports Server (NTRS)
Jefferies, S. M.; Duvall, T. L., Jr.
1991-01-01
A measurement of the intensity distribution in an image of the solar disk will be corrupted by a spatial redistribution of the light that is caused by the earth's atmosphere and the observing instrument. A simple correction method is introduced here that is applicable for solar p-mode intensity observations obtained over a period of time in which there is a significant change in the scattering component of the point spread function. The method circumvents the problems incurred with an accurate determination of the spatial point spread function and its subsequent deconvolution from the observations. The method only corrects the spherical harmonic coefficients that represent the spatial frequencies present in the image and does not correct the image itself.
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Russell, Keith A.; Gibson, Thomas W. G.; Chong, Andrew; Co, Carmon; Koch, Thomas G.
2015-01-01
Background Mesenchymal stromal cells (MSC) are increasingly investigated for their clinical utility in dogs. Fetal bovine serum (FBS) is a common culture supplement used for canine MSC expansion. However, FBS content is variable, its clinical use carries risk of an immune response, and its cost is increasing due to global demand. Platelet lysate (PL) has proven to be a suitable alternative to FBS for expansion of human MSC. Hypothesis and Objectives We hypothesized that canine adipose tissue (AT) and bone marrow (BM) MSC could be isolated and expanded equally in PL and FBS at conventionally-used concentrations with differentiation of these MSC unaffected by choice of supplement. Our objectives were to evaluate the use of canine PL in comparison with FBS at four stages: 1) isolation, 2) proliferation, 3) spontaneous differentiation, and 4) directed differentiation. Results 1) Medium with 10% PL was unable to isolate MSC. 2) MSC, initially isolated in FBS-supplemented media, followed a dose-dependent response with no significant difference between PL and FBS cultures at up to 20% (AT) or 30% (BM) enrichment. Beyond these respective peaks, proliferation fell in PL cultures only, while a continued dose-dependent proliferation response was noted in FBS cultures. 3) Further investigation indicated PL expansion culture was inducing spontaneous adipogenesis in concentrations as low as 10% and as early as 4 days in culture. 4) MSC isolated in FBS, but expanded in either FBS or PL, maintained ability to undergo directed adipogenesis and osteogenesis, but not chondrogenesis. Conclusions/Significance Canine PL did not support establishment of MSC colonies from AT and BM, nor expansion of MSC, which appear to undergo spontaneous adipogenesis in response to PL exposure. In vivo studies are warranted to determine if concurrent use of MSC with any platelet-derived products such as platelet-rich plasma are associated with synergistic, neutral or antagonistic effects. PMID:26353112
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Gray, Andrea; Maguire, Timothy; Schloss, Rene; Yarmush, Martin L
2015-01-01
Induction of therapeutic mesenchymal stromal cell (MSC) function is dependent upon activating factors present in diseased or injured tissue microenvironments. These functions include modulation of macrophage phenotype via secreted molecules including prostaglandin E2 (PGE2). Many approaches aim to optimize MSC-based therapies, including preconditioning using soluble factors and cell immobilization in biomaterials. However, optimization of MSC function is usually inefficient as only a few factors are manipulated in parallel. We utilized fractional factorial design of experiments to screen a panel of 6 molecules (lipopolysaccharide [LPS], polyinosinic-polycytidylic acid [poly(I:C)], interleukin [IL]-6, IL-1β, interferon [IFN]-β, and IFN-γ), individually and in combinations, for the upregulation of MSC PGE2 secretion and attenuation of macrophage secretion of tumor necrosis factor (TNF)-α, a pro-inflammatory molecule, by activated-MSC conditioned medium (CM). We used multivariable linear regression (MLR) and analysis of covariance to determine differences in functions of optimal factors on monolayer MSCs and alginate-encapsulated MSCs (eMSCs). The screen revealed that LPS and IL-1β potently activated monolayer MSCs to enhance PGE2 production and attenuate macrophage TNF-α. Activation by LPS and IL-1β together synergistically increased MSC PGE2, but did not synergistically reduce macrophage TNF-α. MLR and covariate analysis revealed that macrophage TNF-α was strongly dependent on the MSC activation factor, PGE2 level, and macrophage donor but not MSC culture format (monolayer versus encapsulated). The results demonstrate the feasibility and utility of using statistical approaches for higher throughput cell analysis. This approach can be extended to develop activation schemes to maximize MSC and MSC-biomaterial functions prior to transplantation to improve MSC therapies. © 2015 American Institute of Chemical Engineers.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Salamon, Achim, E-mail: achim.salamon@med.uni-rostock.de; Jonitz-Heincke, Anika, E-mail: anika.jonitz@med.uni-rostock.de; Adam, Stefanie, E-mail: stefanie.adam@med.uni-rostock.de
Cartilaginous matrix-degenerative diseases like osteoarthritis (OA) are characterized by gradual cartilage erosion, and also by increased presence of cells with mesenchymal stem cell (MSC) character within the affected tissues. Moreover, primary chondrocytes long since are known to de-differentiate in vitro and to be chondrogenically re-differentiable. Since both findings appear to conflict with each other, we quantitatively assessed the mesenchymal differentiation potential of OA patient cartilage-derived cells (CDC) towards the osteogenic and adipogenic lineage in vitro and compared it to that of MSC isolated from adipose tissue (adMSC) of healthy donors. We analyzed expression of MSC markers CD29, CD44, CD105, andmore » CD166, and, following osteogenic and adipogenic induction in vitro, quantified their expression of osteogenic and adipogenic differentiation markers. Furthermore, CDC phenotype and proliferation were monitored. We found that CDC exhibit an MSC CD marker expression pattern similar to adMSC and a similar increase in proliferation rate during osteogenic differentiation. In contrast, the marked reduction of proliferation observed during adipogenic differentiation of adMSC was absent in CDC. Quantification of differentiation markers revealed a strong osteogenic differentiation potential for CDC, however almost no capacity for adipogenic differentiation. Since in the pathogenesis of OA, cartilage degeneration coincides with high bone turnover rates, the high osteogenic differentiation potential of OA patient-derived CDC may affect clinical therapeutic regimens aiming at autologous cartilage regeneration in these patients. - Highlights: • We analyze the mesenchymal differentiation capacity of cartilage-derived cells (CDC). • CDC express mesenchymal stem cell (MSC) markers CD29, CD44, CD105, and CD166. • CDC and MSC proliferation is reduced in adipogenesis and increased in osteogenesis. • Adipogenic differentiation is virtually absent in CDC, but strong in MSC. • Osteogenic differentiation is significantly stronger for CDC than for MSC.« less
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Clinical-scale expansion of mesenchymal stromal cells: a large banking experience.
Lechanteur, Chantal; Briquet, Alexandra; Giet, Olivier; Delloye, Olivier; Baudoux, Etienne; Beguin, Yves
2016-05-20
Mesenchymal stromal cells (MSC) are largely investigated in clinical trials aiming to control inappropriate immune reactions (GVHD, Crohn's disease, solid organ transplantation). As the percentage of MSC precursors in bone marrow is very low, these must be expanded in vitro to obtain therapeutic cell doses. We describe here the constitution of an allogeneic human third-party MSC bank from screened healthy volunteer donors in compliance with quality specifications and ISCT-release criteria and report follow-up of different aspects of this activity since 2007. 68 clinical-grade large-scale MSC cultures were completed and analyzed. The whole process was described, including volunteer donor screening, bone marrow collection, mononuclear cell isolation and expansion over 4 weeks, harvesting, cryopreservation, release, administration and quality controls of the cells (including microbiology, phenotype, and potency assays). From 59 validated donors, 68 cultures were completed (mean of final yields: 886 × 10(6) cells/culture) and a total of 464 MSC aliquots have been produced and stored in liquid nitrogen (mean of 132.8 × 10(6) cells/bag). Each MSC batch underwent extensive testing to verify its conformity with EBMT and ISCT release criteria and was individually validated. As of June 1 2015, 314 bags have been released and infused to patients included in 6 different clinical protocols. All thawed MSC units satisfied to release criteria and no infusion-related toxicity was reported. In conclusion, despite low passage cultures, we have been able to create an allogeneic "off-the-shelf" MSC bank with a large number of frozen aliquots and report here an efficient clinical-grade MSC banking activity in place for more than 7 years. Our challenge now is to produce MSC in compliance with good manufacturing practices (GMP) as, in the meantime, MSC have become considered as advanced therapy medicinal products (ATMP). Another significant challenge remains the development of relevant potency assay.
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Boos, Anja M; Loew, Johanna S; Deschler, Gloria; Arkudas, Andreas; Bleiziffer, Oliver; Gulle, Heinz; Dragu, Adrian; Kneser, Ulrich; Horch, Raymund E; Beier, Justus P
2011-01-01
Abstract Bone tissue engineering approaches increasingly focus on the use of mesenchymal stem cells (MSC). In most animal transplantation models MSC are isolated and expanded before auto cell transplantation which might be critical for clinical application in the future. Hence this study compares the potential of directly auto-transplanted versus in vitro expanded MSC with or without bone morphogenetic protein-2 (BMP-2) to induce bone formation in a large volume ceramic bone substitute in the sheep model. MSC were isolated from bone marrow aspirates and directly auto-transplanted or expanded in vitro and characterized using fluorescence activated cell sorting (FACS) and RT-PCR analysis before subcutaneous implantation in combination with BMP-2 and β-tricalcium phosphate/hydroxyapatite (β-TCP/HA) granules. Constructs were explanted after 1 to 12 weeks followed by histological and RT-PCR evaluation. Sheep MSC were CD29+, CD44+ and CD166+ after selection by Ficoll gradient centrifugation, while directly auto-transplanted MSC-populations expressed CD29 and CD166 at lower levels. Both, directly auto-transplanted and expanded MSC, were constantly proliferating and had a decreasing apoptosis over time in vivo. Directly auto-transplanted MSC led to de novo bone formation in a heterotopic sheep model using a β-TCP/HA matrix comparable to the application of 60 μg/ml BMP-2 only or implantation of expanded MSC. Bone matrix proteins were up-regulated in constructs following direct auto-transplantation and in expanded MSC as well as in BMP-2 constructs. Up-regulation was detected using immunohistology methods and RT-PCR. Dense vascularization was demonstrated by CD31 immunohistology staining in all three groups. Ectopic bone could be generated using directly auto-transplanted or expanded MSC with β-TCP/HA granules alone. Hence BMP-2 stimulation might become dispensable in the future, thus providing an attractive, clinically feasible approach to bone tissue engineering. PMID:20636333
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Alterations to the relativistic Love-Franey model and their application to inelastic scattering
DOE Office of Scientific and Technical Information (OSTI.GOV)
Zeile, J.R.
The fictitious axial-vector and tensor mesons for the real part of the relativistic Love-Franey interaction are removed. In an attempt to make up for this loss, derivative couplings are used for the {pi} and {rho} mesons. Such derivative couplings require the introduction of axial-vector and tensor contact term corrections. Meson parameters are then fit to free nucleon-nucleon scattering data. The resulting fits are comparable to those of the relativistic Love-Franey model provided that the contact term corrections are included and the fits are weighted over the physically significant quantity of twice the tensor minus the axial-vector Lorentz invariants. Failure tomore » include contact term corrections leads to poor fits at higher energies. The off-shell behavior of this model is then examined by looking at several applications from inelastic proton-nucleus scattering.« less
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A quantitative reconstruction software suite for SPECT imaging
NASA Astrophysics Data System (ADS)
Namías, Mauro; Jeraj, Robert
2017-11-01
Quantitative Single Photon Emission Tomography (SPECT) imaging allows for measurement of activity concentrations of a given radiotracer in vivo. Although SPECT has usually been perceived as non-quantitative by the medical community, the introduction of accurate CT based attenuation correction and scatter correction from hybrid SPECT/CT scanners has enabled SPECT systems to be as quantitative as Positron Emission Tomography (PET) systems. We implemented a software suite to reconstruct quantitative SPECT images from hybrid or dedicated SPECT systems with a separate CT scanner. Attenuation, scatter and collimator response corrections were included in an Ordered Subset Expectation Maximization (OSEM) algorithm. A novel scatter fraction estimation technique was introduced. The SPECT/CT system was calibrated with a cylindrical phantom and quantitative accuracy was assessed with an anthropomorphic phantom and a NEMA/IEC image quality phantom. Accurate activity measurements were achieved at an organ level. This software suite helps increasing quantitative accuracy of SPECT scanners.
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Coherent beam control through inhomogeneous media in multi-photon microscopy
NASA Astrophysics Data System (ADS)
Paudel, Hari Prasad
Multi-photon fluorescence microscopy has become a primary tool for high-resolution deep tissue imaging because of its sensitivity to ballistic excitation photons in comparison to scattered excitation photons. The imaging depth of multi-photon microscopes in tissue imaging is limited primarily by background fluorescence that is generated by scattered light due to the random fluctuations in refractive index inside the media, and by reduced intensity in the ballistic focal volume due to aberrations within the tissue and at its interface. We built two multi-photon adaptive optics (AO) correction systems, one for combating scattering and aberration problems, and another for compensating interface aberrations. For scattering correction a MEMS segmented deformable mirror (SDM) was inserted at a plane conjugate to the objective back-pupil plane. The SDM can pre-compensate for light scattering by coherent combination of the scattered light to make an apparent focus even at a depths where negligible ballistic light remains (i.e. ballistic limit). This problem was approached by investigating the spatial and temporal focusing characteristics of a broad-band light source through strongly scattering media. A new model was developed for coherent focus enhancement through or inside the strongly media based on the initial speckle contrast. A layer of fluorescent beads under a mouse skull was imaged using an iterative coherent beam control method in the prototype two-photon microscope to demonstrate the technique. We also adapted an AO correction system to an existing in three-photon microscope in a collaborator lab at Cornell University. In the second AO correction approach a continuous deformable mirror (CDM) is placed at a plane conjugate to the plane of an interface aberration. We demonstrated that this "Conjugate AO" technique yields a large field-of-view (FOV) advantage in comparison to Pupil AO. Further, we showed that the extended FOV in conjugate AO is maintained over a relatively large axial misalignment of the conjugate planes of the CDM and the aberrating interface. This dissertation advances the field of microscopy by providing new models and techniques for imaging deeply within strongly scattering tissue, and by describing new adaptive optics approaches to extending imaging FOV due to sample aberrations.
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NASA Astrophysics Data System (ADS)
Burress, Jacob; Bethea, Donald; Troub, Brandon
2017-05-01
The accurate measurement of adsorbed gas up to high pressures (˜100 bars) is critical for the development of new materials for adsorbed gas storage. The typical Sievert-type volumetric method introduces accumulating errors that can become large at maximum pressures. Alternatively, gravimetric methods employing microbalances require careful buoyancy corrections. In this paper, we present a combination gravimetric and volumetric system for methane sorption measurements on samples between ˜0.5 and 1 g. The gravimetric method described requires no buoyancy corrections. The tandem use of the gravimetric method allows for a check on the highest uncertainty volumetric measurements. The sources and proper calculation of uncertainties are discussed. Results from methane measurements on activated carbon MSC-30 and metal-organic framework HKUST-1 are compared across methods and within the literature.
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Burress, Jacob; Bethea, Donald; Troub, Brandon
2017-05-01
The accurate measurement of adsorbed gas up to high pressures (∼100 bars) is critical for the development of new materials for adsorbed gas storage. The typical Sievert-type volumetric method introduces accumulating errors that can become large at maximum pressures. Alternatively, gravimetric methods employing microbalances require careful buoyancy corrections. In this paper, we present a combination gravimetric and volumetric system for methane sorption measurements on samples between ∼0.5 and 1 g. The gravimetric method described requires no buoyancy corrections. The tandem use of the gravimetric method allows for a check on the highest uncertainty volumetric measurements. The sources and proper calculation of uncertainties are discussed. Results from methane measurements on activated carbon MSC-30 and metal-organic framework HKUST-1 are compared across methods and within the literature.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Cappa, Christopher D.; Kolesar, Katheryn R.; Zhang, Xiaolu
2016-01-01
Measurements of the optical properties (absorption, scattering and extinction) of PM 1, PM 2.5 and PM 10 made at two sites around Sacramento, CA, during the June 2010 Carbonaceous Aerosols and Radiative Effects Study (CARES) are reported. These observations are used to establish relationships between various intensive optical properties and to derive information about the dependence of the optical properties on photochemical aging and sources. Supermicron particles contributed substantially to the total light scattering at both sites, about 50 % on average. A strong, linear relationship is observed between the scattering Ångström exponent for PM 10 and the fraction of the scatteringmore » that is contributed by submicron particles ( f sca, PM 1 ) at both sites and with similar slopes and intercepts (for a given pair of wavelengths), suggesting that the derived relationship may be generally applicable for understanding variations in particle size distributions from remote sensing measurements. At the more urban T0 site, the f sca, PM 1 increased with photochemical age, whereas at the downwind, more rural T1 site the f sca, PM 1 decreased slightly with photochemical age. This difference in behavior reflects differences in transport, local production and local emission of supermicron particles between the sites. Light absorption is dominated by submicron particles, but there is some absorption by supermicron particles (~15 % of the total). The supermicron absorption derives from a combination of black carbon that has penetrated into the supermicron mode and from dust, and there is a clear increase in the mass absorption coefficient of just the supermicron particles with increasing average particle size. The mass scattering coefficient (MSC) for the supermicron particles was directly observed to vary inversely with the average particle size, demonstrating that MSC cannot always be treated as a constant in estimating mass concentrations from scattering measurements, or vice versa. The total particle backscatter fraction exhibited some dependence upon the relative abundance of sub- versus supermicron particles; however this was modulated by variations in the median size of particles within a given size range; variations in the submicron size distribution had a particularly large influence on the observed backscatter efficiency and an approximate method to account for this variability is introduced. The relationship between the absorption and scattering Ångström exponents is examined and used to update a previously suggested particle classification scheme. Differences in composition led to differences in the sensitivity of PM 2.5 to heating in a thermodenuder to the average particle size, with more extensive evaporation (observed as a larger decrease in the PM 2.5 extinction coefficient) corresponding to smaller particles; i.e., submicron particles were generally more susceptible to heating than the supermicron particles. The influence of heating on the particle hygroscopicity varied with the effective particle size, with larger changes observed when the PM 2.5 distribution was dominated by smaller particles.« less
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Becherucci, Valentina; Piccini, Luisa; Casamassima, Serena; Bisin, Silvia; Gori, Valentina; Gentile, Francesca; Ceccantini, Riccardo; De Rienzo, Elena; Bindi, Barbara; Pavan, Paola; Cunial, Vanessa; Allegro, Elisa; Ermini, Stefano; Brugnolo, Francesca; Astori, Giuseppe; Bambi, Franco
2018-05-02
The use of platelet lysate (PL) for the ex-vivo expansion of mesenchymal stromal/stem cells (MSCs) was initially proposed by Doucet et al. in 2005, as an alternative to animal serum. Moreover, regulatory authorities discourage the use of fetal bovine serum (FBS) or other animal derivatives, to avoid risk of zoonoses and xenogeneic immune reactions. Even if many studies investigated PL composition, there still are some open issues related to its use in ex-vivo MSC expansion, especially according to good manufacturing practice (GMP) grade protocols. As an authorized cell factory, we report our experience using standardized PL produced by Azienda Ospedaliero Universitaria Meyer Transfusion Service for MSC expansion according to a GMP grade clinical protocol. As suggested by other authors, we performed an in-vitro test on MSCs versus MSCs cultured with FBS that still represents the best way to test PL batches. We compared 12 MSC batches cultured with DMEM 5% PL with similar batches cultured with DMEM 10% FBS, focusing on the MSC proliferation rate, MSC surface marker expression, MSC immunomodulatory and differentiation potential, and finally MSC relative telomere length. Results confirmed the literature data as PL increases cell proliferation without affecting the MSC immunophenotype, immunomodulatory potential, differentiation potential and relative telomere length. PL can be considered a safe alternative to FBS for ex-vivo expansion of MSC according to a GMP grade protocol. Our experience confirms the literature data: a large number of MSCs for clinical applications can be obtained by expansion with PL, without affecting the MSC main features. Our experience underlines the benefits of a close collaboration between the PL producers (transfusion service) and the end users (cell factory) in a synergy of skills and experiences that can lead to standardized PL production.
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Sestini, Stefano; Boeri, Mattia; Marchiano, Alfonso; Pelosi, Giuseppe; Galeone, Carlotta; Verri, Carla; Suatoni, Paola; Sverzellati, Nicola; La Vecchia, Carlo; Sozzi, Gabriella; Pastorino, Ugo
2015-10-20
Liquid biopsies can detect biomarkers carrying information on the development and progression of cancer. We demonstrated that a 24 plasma-based microRNA signature classifier (MSC) was capable of increasing the specificity of low dose computed tomography (LDCT) in a lung cancer screening trial. In the present study, we tested the prognostic performance of MSC, and its ability to monitor disease status recurrence in LDCT screening-detected lung cancers.Between 2000 and 2010, 3411 heavy smokers enrolled in two screening programmes, underwent annual or biennial LDCT. During the first five years of screening, 84 lung cancer patients were classified according to one of the three MSC levels of risk: high, intermediate or low. Kaplan-Meier survival analysis was performed according to MSC and clinico-pathological information. Follow-up MSC analysis was performed on longitudinal plasma samples (n = 100) collected from 31 patients before and after surgical resection.Five-year survival was 88.9% for low risk, 79.5% for intermediate risk and 40.1% for high risk MSC (p = 0.001). The prognostic power of MSC persisted after adjusting for tumor stage (p = 0.02) and when the analysis was restricted to LDCT-detected cases after exclusion of interval cancers (p < 0.001). The MSC risk level decreased after surgery in 76% of the 25 high-intermediate subjects who remained disease free, whereas in relapsing patients an increase of the MSC risk level was observed at the time of detection of second primary tumor or metastatic progression.These results encourage exploiting the MSC test for lung cancer monitoring in LDCT screening for lung cancer.
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Matuskova, Miroslava; Kozovska, Zuzana; Toro, Lenka; Durinikova, Erika; Tyciakova, Silvia; Cierna, Zuzana; Bohovic, Roman; Kucerova, Lucia
2015-04-09
Metastatic spread of tumor cells remains a serious problem in cancer treatment. Gene-directed enzyme/prodrug therapy mediated by tumor-homing genetically engineered mesenchymal stromal cells (MSC) represents a promising therapeutic modality for elimination of disseminated cells. Efficacy of gene-directed enzyme/prodrug therapy can be improved by combination of individual systems. We aimed to define the combination effect of two systems of gene therapy mediated by MSC, and evaluate the ability of systemically administered genetically engineered mesenchymal stromal cells to inhibit the growth of experimental metastases derived from human breast adenocarcinoma cells MDA-MB-231/EGFP. Human adipose tissue-derived mesenchymal stromal cells (AT-MSC) were retrovirally transduced with fusion yeast cytosine deaminase::uracil phosphoribosyltransferase (CD::UPRT) or with Herpes simplex virus thymidine kinase (HSVtk). Engineered MSC were cocultured with tumor cells in the presence of prodrugs 5-fluorocytosin (5-FC) and ganciclovir (GCV). Combination effect of these enzyme/prodrug approaches was calculated. SCID/bg mice bearing experimental lung metastases were treated with CD::UPRT-MSC, HSVtk-MSC or both in combination in the presence of respective prodrug(s). Treatment efficiency was evaluated by EGFP-positive cell detection by flow cytometry combined with real-time PCR quantification of human cells in mouse organs. Results were confirmed by histological and immunohistochemical examination. We demonstrated various extent of synergy depending on tested cell line and experimental setup. The strongest synergism was observed on breast cancer-derived cell line MDA-MB-231/EGFP. Systemic administration of CD::UPRT-MSC and HSVtk-MSC in combination with 5-FC and GCV inhibited growth of MDA-MB-231 induced lung metastases. Combined gene-directed enzyme/prodrug therapy mediated by MSC exerted synergic cytotoxic effect and resulted in high therapeutic efficacy in vivo.
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Canine and Equine Mesenchymal Stem Cells Grown in Serum Free Media Have Altered Immunophenotype.
Clark, Kaitlin C; Kol, Amir; Shahbenderian, Salpi; Granick, Jennifer L; Walker, Naomi J; Borjesson, Dori L
2016-04-01
Mesenchymal stem cell (MSC) therapy is being increasingly used to treat dogs and horses with naturally-occurring diseases. However these animals also serve as critical large animal models for ongoing translation of cell therapy products to the human market. MSC manufacture for clinical use mandates improvement in cell culture systems to meet demands for higher MSC numbers and removal of xeno-proteins (i.e. fetal bovine serum, FBS). While serum-free media (SFM) is commercially available, its affects on MSC phenotype and immunomodulatory functions are not fully known. The objective of this study was to determine if specific MSC culture conditions, MSC expansion in HYPERFlasks® or MSC expansion in a commercially available SFM, would alter MSC proliferation, phenotype or immunomodulatory properties in vitro. MSCs cultured in HYPERFlasks® were similar in phenotype, proliferative capacity and immunomodulatory functions to MSCs grown in standard flasks however MSC yield was markedly increased. HYPERFlasks® therefore provide a viable option to generate greater cell numbers in a streamlined manner. Canine and equine MSCs expanded in SFM displayed similar proliferation, surface phenotype and inhibitory effect on lymphocyte proliferation in vitro. However, MSCs cultured in the absence of FBS secreted significantly less PGE2, and were significantly less able to inhibit IFNγ secretion by activated T-cells. Immunomodulatory functions altered by expansion in SFM were species dependent. Unlike equine MSCs, in canine adipose-derived MSCs, the inhibition of lymphocyte proliferation was not principally modulated by PGE2. The removal of FBS from both canine and equine MSC culture systems resulted in altered immunomodulatory properties in vitro and warrants further investigation prior to moving towards FBS-free culture conditions.
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Saulnier, N; Viguier, E; Perrier-Groult, E; Chenu, C; Pillet, E; Roger, T; Maddens, S; Boulocher, C
2015-01-01
The anti-inflammatory and anti-catabolic effects of neonatal Mesenchymal Stromal Cell (MSC) were investigated in a xenogeneic model of mild osteoarthritis (OA). The paracrine properties of MSC on synoviocytes were further investigated in vitro. OA was induced by medial meniscal release (MMR) in 30 rabbit knees. A single early (day 3) or delayed (day 15) intra-articular (IA) injection of MSC isolated from equine Umbilical Cord Wharton's jelly (UC-MSC) was performed. Rabbits were euthanized on days 15 or 56. OA grading was performed and gene expression of inflammatory cytokines and metalloproteinases was measured in synovial tissue. Paracrine effects of UC-MSC were investigated using UC-conditioned vs control medium on rabbit primary synoviocytes stimulated with interleukin 1 beta in vitro. No adverse local or systemic responses were observed clinically after xenogeneic UC-MSC injection. At study end point, cartilage fibrillation was lower in early treatment than in delayed treatment group. Cellular infiltrate was observed in the synovium of both UC-MSC groups. OA synovium exhibited a reduced expression of metalloproteinases-1, -3, -13 in the early cell-treated group at d56. In vitro, UC-conditioned medium exerted anti-inflammatory and anti-catabolic effects on synoviocytes exposed to pro-inflammatory stimulus. Early IA injection of equine UC-MSC was effective in preventing OA signs in rabbit knees following MMR. UC-MSC target the synovium and modulate the gene expression pattern of synoviocytes to promote an anti-catabolic environment. This confirms the synovium is a major target and mediator of MSC therapy, modulating the expression of matrix-degrading enzymes. Copyright © 2014 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.
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Ma, Anlun; Jiang, Li; Song, Lijun; Hu, Yanxin; Dun, Hao; Daloze, Pierre; Yu, Yonglin; Jiang, Jianyuan; Zafarullah, Muhammad; Chen, Huifang
2013-07-01
Articular cartilage defects are commonly associated with trauma, inflammation and osteoarthritis. Mesenchymal stem cell (MSC)-based therapy is a promising novel approach for repairing articular cartilage. Direct intra-articular injection of uncommitted MSCs does not regenerate high-quality cartilage. This study explored utilization of a new three-dimensional, selected chondrogenic clonal MSC-loaded monkey acellular dermal matrix (MSC-ADM) scaffold to repair damaged cartilage in an experimental model of knee joint cartilage defect in Cynomolgus monkeys. MSCs were characterized for cell size, cell yield, phenotypes, proliferation and chondrogenic differentiation capacity. Chondrogenic differentiation assays were performed at different MSC passages by sulfated glycosaminoglycans (sGAG), collagen, and fluorescence activated cell sorter (FACS) analysis. Selected chondrogenic clonal MSCs were seeded onto ADM scaffold with the sandwich model and MSC-loaded ADM grafts were analyzed by confocal microscopy and scanning electron microscopy. Cartilage defects were treated with normal saline, clonal MSCs and clonal MSC-ADM grafts, respectively. The clinical parameters, and histological and immunohistochemical examinations were evaluated at weeks 8, 16, 24 post-treatment, respectively. Polyclonal and clonal MSCs could differentiate into the chondrogenic lineage after stimulation with suitable chondrogenic factors. They expressed mesenchymal markers and were negative for hematopoietic markers. Articular cartilage defects were considerably improved and repaired by selected chondrogenic clonal MSC-based treatment, particularly, in MSC-ADM-treated group. The histological scores in MSC-ADM-treated group were consistently higher than those of other groups. Our results suggest that selected chondrogenic clonal MSC-loaded ADM grafts could improve the cartilage lesions in Cynomolgus monkey model, which may be applicable for repairing similar human cartilage defects. Copyright © 2013 Elsevier B.V. All rights reserved.
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Jakobsen, Rune B; Shahdadfar, Aboulghassem; Reinholt, Finn P; Brinchmann, Jan E
2010-10-01
Treatment of focal lesions of the articular cartilage of the knee using chondrocytes in a hyaluronic acid (HA) scaffold is already being investigated in clinical trials. An alternative may be to use mesenchymal stem cells (MSC). We have compared articular chondrocytes with MSC from human bone marrow (BM) and adipose tissue (AT), all cultured in HA scaffolds, for their ability to express genes and synthesize proteins associated with chondrogenesis. The cells were expanded in monolayer cultures. After seeding into the scaffold, the chondrocytes were maintained in medium, while the two MSC populations were given a chondrogenic differentiation medium. Chondrogenesis was assessed by real-time RT-PCR for chondrocyte-associated genes, by immunohistochemistry and by ELISA for collagens in the supernatant. Redifferentiation of the dedifferentiated chondrocytes in the HA scaffold was shown by a modest increase in type II collagen mRNA (COL2A1) and reduction in COL1A1. BM-MSC expressed 600-fold higher levels of COL2A1 than chondrocytes after 3 weeks in the scaffold. The levels of aggrecan (AGC1) and COL1A1 were similar for chondrocyte and BM-MSC scaffold cultures, while COL10A1 was higher in the BM-MSC. AT-MSC expressed levels of COL2A1 and COL1A1 similar to chondrocytes, but less AGC1 and COL10A1. Surprisingly, little collagen II protein was observed in the scaffold. Instead, collagen II was found in the culture medium. Chondrogenesis in HA scaffolds was more efficient using BM-MSC than AT-MSC or chondrocytes. Some of the secreted collagen II escaped entrapment in the extracellular space and was detected in the culture medium.
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Ionescu, Lavinia; Byrne, Roisin N; van Haaften, Tim; Vadivel, Arul; Alphonse, Rajesh S; Rey-Parra, Gloria J; Weissmann, Gaia; Hall, Adam; Eaton, Farah; Thébaud, Bernard
2012-12-01
Mortality and morbidity of acute lung injury and acute respiratory distress syndrome remain high because of the lack of pharmacological therapies to prevent injury or promote repair. Mesenchymal stem cells (MSCs) prevent lung injury in various experimental models, despite a low proportion of donor-derived cell engraftment, suggesting that MSCs exert their beneficial effects via paracrine mechanisms. We hypothesized that soluble factors secreted by MSCs promote the resolution of lung injury in part by modulating alveolar macrophage (AM) function. We tested the therapeutic effect of MSC-derived conditioned medium (CdM) compared with whole MSCs, lung fibroblasts, and fibroblast-CdM. Intratracheal MSCs and MSC-CdM significantly attenuated lipopolysaccharide (LPS)-induced lung neutrophil influx, lung edema, and lung injury as assessed by an established lung injury score. MSC-CdM increased arginase-1 activity and Ym1 expression in LPS-exposed AMs. In vivo, AMs from LPS-MSC and LPS-MSC CdM lungs had enhanced expression of Ym1 and decreased expression of inducible nitric oxide synthase compared with untreated LPS mice. This suggests that MSC-CdM promotes alternative macrophage activation to an M2 "healer" phenotype. Comparative multiplex analysis of MSC- and fibroblast-CdM demonstrated that MSC-CdM contained several factors that may confer therapeutic benefit, including insulin-like growth factor I (IGF-I). Recombinant IGF-I partially reproduced the lung protective effect of MSC-CdM. In summary, MSCs act through a paracrine activity. MSC-CdM promotes the resolution of LPS-induced lung injury by attenuating lung inflammation and promoting a wound healing/anti-inflammatory M2 macrophage phenotype in part via IGF-I.
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Ionescu, Lavinia; Byrne, Roisin N.; van Haaften, Tim; Vadivel, Arul; Alphonse, Rajesh S.; Rey-Parra, Gloria J.; Weissmann, Gaia; Hall, Adam; Eaton, Farah
2012-01-01
Mortality and morbidity of acute lung injury and acute respiratory distress syndrome remain high because of the lack of pharmacological therapies to prevent injury or promote repair. Mesenchymal stem cells (MSCs) prevent lung injury in various experimental models, despite a low proportion of donor-derived cell engraftment, suggesting that MSCs exert their beneficial effects via paracrine mechanisms. We hypothesized that soluble factors secreted by MSCs promote the resolution of lung injury in part by modulating alveolar macrophage (AM) function. We tested the therapeutic effect of MSC-derived conditioned medium (CdM) compared with whole MSCs, lung fibroblasts, and fibroblast-CdM. Intratracheal MSCs and MSC-CdM significantly attenuated lipopolysaccharide (LPS)-induced lung neutrophil influx, lung edema, and lung injury as assessed by an established lung injury score. MSC-CdM increased arginase-1 activity and Ym1 expression in LPS-exposed AMs. In vivo, AMs from LPS-MSC and LPS-MSC CdM lungs had enhanced expression of Ym1 and decreased expression of inducible nitric oxide synthase compared with untreated LPS mice. This suggests that MSC-CdM promotes alternative macrophage activation to an M2 “healer” phenotype. Comparative multiplex analysis of MSC- and fibroblast-CdM demonstrated that MSC-CdM contained several factors that may confer therapeutic benefit, including insulin-like growth factor I (IGF-I). Recombinant IGF-I partially reproduced the lung protective effect of MSC-CdM. In summary, MSCs act through a paracrine activity. MSC-CdM promotes the resolution of LPS-induced lung injury by attenuating lung inflammation and promoting a wound healing/anti-inflammatory M2 macrophage phenotype in part via IGF-I. PMID:23023971
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NASA Astrophysics Data System (ADS)
Mobberley, Sean David
Accurate, cross-scanner assessment of in-vivo air density used to quantitatively assess amount and distribution of emphysema in COPD subjects has remained elusive. Hounsfield units (HU) within tracheal air can be considerably more positive than -1000 HU. With the advent of new dual-source scanners which employ dedicated scatter correction techniques, it is of interest to evaluate how the quantitative measures of lung density compare between dual-source and single-source scan modes. This study has sought to characterize in-vivo and phantom-based air metrics using dual-energy computed tomography technology where the nature of the technology has required adjustments to scatter correction. Anesthetized ovine (N=6), swine (N=13: more human-like rib cage shape), lung phantom and a thoracic phantom were studied using a dual-source MDCT scanner (Siemens Definition Flash. Multiple dual-source dual-energy (DSDE) and single-source (SS) scans taken at different energy levels and scan settings were acquired for direct quantitative comparison. Density histograms were evaluated for the lung, tracheal, water and blood segments. Image data were obtained at 80, 100, 120, and 140 kVp in the SS mode (B35f kernel) and at 80, 100, 140, and 140-Sn (tin filtered) kVp in the DSDE mode (B35f and D30f kernels), in addition to variations in dose, rotation time, and pitch. To minimize the effect of cross-scatter, the phantom scans in the DSDE mode was obtained by reducing the tube current of one of the tubes to its minimum (near zero) value. When using image data obtained in the DSDE mode, the median HU values in the tracheal regions of all animals and the phantom were consistently closer to -1000 HU regardless of reconstruction kernel (chapters 3 and 4). Similarly, HU values of water and blood were consistently closer to their nominal values of 0 HU and 55 HU respectively. When using image data obtained in the SS mode the air CT numbers demonstrated a consistent positive shift of up to 35 HU with respect to the nominal -1000 HU value. In vivo data demonstrated considerable variability in tracheal, influenced by local anatomy with SS mode scanning while tracheal air was more consistent with DSDE imaging. Scatter effects in the lung parenchyma differed from adjacent tracheal measures. In summary, data suggest that enhanced scatter correction serves to provide more accurate CT lung density measures sought to quantitatively assess the presence and distribution of emphysema in COPD subjects. Data further suggest that CT images, acquired without adequate scatter correction, cannot be corrected by linear algorithms given the variability in tracheal air HU values and the independent scatter effects on lung parenchyma.
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High-Throughput Simulations Reveal Membrane-Mediated Effects of Alcohols on MscL Gating
2017-01-01
The mechanosensitive channels of large conductance (MscL) are bacterial membrane proteins that serve as last resort emergency release valves in case of severe osmotic downshock. Sensing bilayer tension, MscL channels are sensitive to changes in the bilayer environment and are, therefore, an ideal test case for exploring membrane protein coupling. Here, we use high-throughput coarse-grained molecular dynamics simulations to characterize MscL gating kinetics in different bilayer environments under the influence of alcohols. We performed over five hundred simulations to obtain sufficient statistics to reveal the subtle effects of changes in the membrane environment on MscL gating. MscL opening times were found to increase with the addition of the straight-chain alcohols ethanol, octanol, and to some extent dodecanol but not with hexadecanol. Increasing concentration of octanol increased the impeding effect, but only up to 10–20 mol %. Our in silico predictions were experimentally confirmed using reconstituted MscL in a liposomal fluorescent efflux assay. Our combined data reveal that the effect of alcohols on MscL gating arises not through specific binding sites but through a combination of the alcohol-induced changes to a number of bilayer properties and their alteration of the MscL–bilayer interface. Our work provides a key example of how extensive molecular simulations can be used to predict the functional modification of membrane proteins by subtle changes in their bilayer environment. PMID:28122455
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High-throughput simulations reveal membrane-mediated effects of alcohols on MscL gating
Melo, Manuel N.; Arnarez, Clement; Sikkema, Hendrik; ...
2017-01-26
The mechanosensitive channels of large conductance (MscL) are bacterial membrane proteins that serve as last resort emergency release valves in case of severe osmotic downshock. Sensing bilayer tension, MscL channels are sensitive to changes in the bilayer environment and are, therefore, an ideal test case for exploring membrane protein coupling. Here, we use high-throughput coarse-grained molecular dynamics simulations to characterize MscL gating kinetics in different bilayer environments under the influence of alcohols. We performed over five hundred simulations to obtain sufficient statistics to reveal the subtle effects of changes in the membrane environment on MscL gating. MscL opening times weremore » found to increase with the addition of the straight-chain alcohols ethanol, octanol, and to some extent dodecanol but not with hexadecanol. Increasing concentration of octanol increased the impeding effect, but only up to 10–20 mol %. Our in silico predictions were experimentally confirmed using reconstituted MscL in a liposomal fluorescent efflux assay. Our combined data reveal that the effect of alcohols on MscL gating arises not through specific binding sites but through a combination of the alcohol-induced changes to a number of bilayer properties and their alteration of the MscL–bilayer interface. Finally, our work provides a key example of how extensive molecular simulations can be used to predict the functional modification of membrane proteins by subtle changes in their bilayer environment.« less
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Drela, Katarzyna; Lech, Wioletta; Figiel-Dabrowska, Anna; Zychowicz, Marzena; Mikula, Michał; Sarnowska, Anna; Domanska-Janik, Krystyna
2016-04-01
Substantial inconsistencies in mesenchymal stem (stromal) cell (MSC) therapy reported in early translational and clinical studies may indicate need for selection of the proper cell population for any particular therapeutic purpose. In the present study we have examined stromal stem cells derived either from umbilical cord Wharton's Jelly (WJ-MSC) or bone marrow (BM-MSC) of adult, healthy donors. The cells characterized in accordance with the International Society for Cellular Therapy (ISCT) indications as well as other phenotypic and functional parameters have been compared under strictly controlled culture conditions. WJ-MSC, in comparison with BM-MSC, exhibited a higher proliferation rate, a greater expansion capability being additionally stimulated under low-oxygen atmosphere, enhanced neurotrophic factors gene expression and spontaneous tendency toward a neural lineage differentiation commitment confirmed by protein and gene marker induction. Our data suggest that WJ-MSC may represent an example of immature-type "pre-MSC," where a substantial cellular component is embryonic-like, pluripotent derivatives with the default neural-like differentiation. These cells may contribute in different extents to nearly all classical MSC populations adversely correlated with the age of cell donors. Our data suggest that neuro-epithelial markers, like nestin, stage specific embryonic antigens-4 or α-smooth muscle actin expressions, may serve as useful indicators of MSC culture neuro-regeneration-associated potency. Copyright © 2016 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.
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Electroweak radiative corrections to neutrino scattering at NuTeV
NASA Astrophysics Data System (ADS)
Park, Kwangwoo; Baur, Ulrich; Wackeroth, Doreen
2007-04-01
The W boson mass extracted by the NuTeV collaboration from the ratios of neutral and charged-current neutrino and anti-neutrino cross sections differs from direct measurements performed at LEP2 and the Fermilab Tevatron by about 3 σ. Several possible sources for the observed difference have been discussed in the literature, including new physics beyond the Standard Model (SM). However, in order to be able to pin down the cause of this discrepancy and to interpret this result as a deviation to the SM, it is important to include the complete electroweak one-loop corrections when extracting the W boson mass from neutrino scattering cross sections. We will present results of a Monte Carlo program for νN (νN) scattering including the complete electroweak O(α) corrections, which will be used to study the effects of these corrections on the extracted values for the electroweak parameters. We will briefly introduce some of the newly developed computational tools for generating Feynman diagrams and corresponding analytic expressions for one-loop matrix elements.
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Joddar, Binata; Kumar, Shweta Anil; Kumar, Alok
2018-06-01
Adult stem cells such as mesenchymal stem cells (MSC) are known to possess the ability to augment neovascularization processes and are thus widely popular as an autologous source of progenitor cells. However there is a huge gap in our current knowledge of mechanisms involved in differentiating MSC into endothelial cells (EC), essential for lining engineered blood vessels. To fill up this gap, we attempted to differentiate human MSC into EC, by culturing the former onto chemically fixed layers of EC or its ECM, respectively. We expected direct contact of MSC when cultured atop fixed EC or its ECM, would coax the former to differentiate into EC. Results showed that human MSC cultured atop chemically fixed EC or its ECM using EC-medium showed enhanced expression of CD31, a marker for EC, compared to other cases. Further in all human MSC cultured using EC-medium, typically characteristic cobble stone shaped morphologies were noted in comparison to cells cultured using MSC medium, implying that the differentiated cells were sensitive to soluble VEGF supplementation present in the EC-medium. Results will enhance and affect therapies utilizing autologous MSC as a cell source for generating vascular cells to be used in a variety of tissue engineering applications.
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Kulterer, Birgit; Friedl, Gerald; Jandrositz, Anita; Sanchez-Cabo, Fatima; Prokesch, Andreas; Paar, Christine; Scheideler, Marcel; Windhager, Reinhard; Preisegger, Karl-Heinz; Trajanoski, Zlatko
2007-03-12
Human mesenchymal stem cells (MSC) with the capacity to differentiate into osteoblasts provide potential for the development of novel treatment strategies, such as improved healing of large bone defects. However, their low frequency in bone marrow necessitate ex vivo expansion for further clinical application. In this study we asked if MSC are developing in an aberrant or unwanted way during ex vivo long-term cultivation and if artificial cultivation conditions exert any influence on their stem cell maintenance. To address this question we first developed human oligonucleotide microarrays with 30.000 elements and then performed large-scale expression profiling of long-term expanded MSC and MSC during differentiation into osteoblasts. The results showed that MSC did not alter their osteogenic differentiation capacity, surface marker profile, and the expression profiles of MSC during expansion. Microarray analysis of MSC during osteogenic differentiation identified three candidate genes for further examination and functional analysis: ID4, CRYAB, and SORT1. Additionally, we were able to reconstruct the three developmental phases during osteoblast differentiation: proliferation, matrix maturation, and mineralization, and illustrate the activation of the SMAD signaling pathways by TGF-beta2 and BMPs. With a variety of assays we could show that MSC represent a cell population which can be expanded for therapeutic applications.
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Exosomes derived from human mesenchymal stem cells confer drug resistance in gastric cancer
Ji, Runbi; Zhang, Bin; Zhang, Xu; Xue, Jianguo; Yuan, Xiao; Yan, Yongmin; Wang, Mei; Zhu, Wei; Qian, Hui; Xu, Wenrong
2015-01-01
Mesenchymal stem cells (MSCs) play an important role in chemoresistance. Exosomes have been reported to modify cellular phenotype and function by mediating cell-cell communication. In this study, we aimed to investigate whether exosomes derived from MSCs (MSC-exosomes) are involved in mediating the resistance to chemotherapy in gastric cancer and to explore the underlying molecular mechanism. We found that MSC-exosomes significantly induced the resistance of gastric cancer cells to 5-fluorouracil both in vivo and ex vivo. MSC-exosomes antagonized 5-fluorouracil-induced apoptosis and enhanced the expression of multi-drug resistance associated proteins, including MDR, MRP and LRP. Mechanistically, MSC-exosomes triggered the activation of calcium/calmodulin-dependent protein kinases (CaM-Ks) and Raf/MEK/ERK kinase cascade in gastric cancer cells. Blocking the CaM-Ks/Raf/MEK/ERK pathway inhibited the promoting role of MSC-exosomes in chemoresistance. Collectively, MSC-exosomes could induce drug resistance in gastric cancer cells by activating CaM-Ks/Raf/MEK/ERK pathway. Our findings suggest that MSC-exosomes have profound effects on modifying gastric cancer cells in the development of drug resistance. Targeting the interaction between MSC-exosomes and cancer cells may help improve the efficacy of chemotherapy in gastric cancer. PMID:26091251
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Exosomes derived from human mesenchymal stem cells confer drug resistance in gastric cancer.
Ji, Runbi; Zhang, Bin; Zhang, Xu; Xue, Jianguo; Yuan, Xiao; Yan, Yongmin; Wang, Mei; Zhu, Wei; Qian, Hui; Xu, Wenrong
2015-08-03
Mesenchymal stem cells (MSCs) play an important role in chemoresistance. Exosomes have been reported to modify cellular phenotype and function by mediating cell-cell communication. In this study, we aimed to investigate whether exosomes derived from MSCs (MSC-exosomes) are involved in mediating the resistance to chemotherapy in gastric cancer and to explore the underlying molecular mechanism. We found that MSC-exosomes significantly induced the resistance of gastric cancer cells to 5-fluorouracil both in vivo and ex vivo. MSC-exosomes antagonized 5-fluorouracil-induced apoptosis and enhanced the expression of multi-drug resistance associated proteins, including MDR, MRP and LRP. Mechanistically, MSC-exosomes triggered the activation of calcium/calmodulin-dependent protein kinases (CaM-Ks) and Raf/MEK/ERK kinase cascade in gastric cancer cells. Blocking the CaM-Ks/Raf/MEK/ERK pathway inhibited the promoting role of MSC-exosomes in chemoresistance. Collectively, MSC-exosomes could induce drug resistance in gastric cancer cells by activating CaM-Ks/Raf/MEK/ERK pathway. Our findings suggest that MSC-exosomes have profound effects on modifying gastric cancer cells in the development of drug resistance. Targeting the interaction between MSC-exosomes and cancer cells may help improve the efficacy of chemotherapy in gastric cancer.
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Biomimetic chimeric peptide-tethered hydrogels for human mesenchymal stem cell delivery.
Shim, Gayong; Kim, Gunwoo; Choi, Junhyeok; Yi, TacGhee; Cho, Yun Kyoung; Song, Sun Uk; Byun, Youngro; Oh, Yu-Kyoung
2015-12-01
Here, we report a chimeric peptide-tethered fibrin hydrogel scaffold for delivery of human mesenchymal stem cells (hMSC). Osteopontin-derived peptide (OP) was used as an hMSC-tethering moiety. OP showed hMSC adhesion properties and enhanced hMSC proliferation. A natural fibrin-binding protein-derived peptide (FBP) was tested for its ability to tether hMSC to the fibrin gel matrix. FBP loading on fibrin gels was 8.2-fold higher than that of a scrambled peptide (scFBP). FBP-loaded fibrin gels were retained at injection sites longer than scFBP-loaded fibrin gels, showing a 15.9-fold higher photon intensity of fluorescent FBP-grafted fibrin gels than fluorescent scFBP-loaded fibrin gels 48 h after injection. On the basis of the fibrin gel-binding properties of FBP and the hMSC-binding and proliferation-supporting properties of OP, we constructed chimeric peptides containing FBP and OP linked with a spacer (FBPsOP). Four days after transplantation, the survival of hMSC in FBPsOP-grafted fibrin gels was 3.9-fold higher than hMSC in fibrin gels alone. Our results suggest the potential of FBPsOP-grafted fibrin gels as a bioactive delivery system for enhanced survival of stem cells. Copyright © 2015 Elsevier B.V. All rights reserved.
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First Apollo 11 sample return containers arrive at Ellington AFB
NASA Technical Reports Server (NTRS)
1969-01-01
The first Apollo 11 sample return container, containing lunar surface material, arrives at Ellington Air Force Base by air from the Pacific recovery area. Happily posing for photographs with the rock box are (left to right) George M. Low, Manager, Apollo Spacecraft Program, Manned Spacecraft Center (MSC); U.S. Air Force Lt. Gen. Samuel C. Phillips, Apollo Program Director, Office of Manned Space Flight, NASA HQ.; George S. Trimble, MSC Deputy Director (almost obscured); Eugene G. Edmonds, MSC Photographic Technology Laboratory; RIchard S. Johnston (in back), Special Assistant to the MSC Director; Dr. Thomas O. Paine, NASA Administrator; and Dr. Robert R. Gilruth, MSC Director.
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Neumann, Anne; Lavrentieva, Antonina; Heilkenbrinker, Alexandra; Loenne, Maren; Kasper, Cornelia
2014-11-27
Recruitment of mesenchymal stromal cells (MSC) into the field of tissue engineering is a promising development since these cells can be expanded vivo to clinically relevant numbers and, after expansion, retain their ability to differentiate into various cell lineages. Safety requirements and the necessity to obtain high cell numbers without frequent subcultivation of cells raised the question of the possibility of expanding MSC in one-way (single-use) disposable bioreactors. In this study, umbilical cord-derived MSC (UC-MSC) were expanded in a disposable Z 2000 H bioreactor under dynamic conditions. Z was characterized regarding residence time and mixing in order to evaluate the optimal bioreactor settings, enabling optimal mass transfer in the absence of shear stress, allowing an reproducible expansion of MSC, while maintaining their stemness properties. Culture of the UC-MSC in disposable Z 2000 H bioreactor resulted in a reproducible 8-fold increase of cell numbers after 5 days. Cells were shown to maintain specific MSC surface marker expression as well as trilineage differentiation potential and lack stress-induced premature senescence.
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Ishihara, Seiichiro; Inman, David R; Li, Wan-Ju; Ponik, Suzanne M; Keely, Patricia J
2017-11-15
In response to chemical stimuli from cancer cells, mesenchymal stem cells (MSC) can differentiate into cancer-associated fibroblasts (CAF) and promote tumor progression. How mechanical stimuli such as stiffness of the extracellular matrix (ECM) contribute to MSC phenotype in cancer remains poorly understood. Here, we show that ECM stiffness leads to mechano-signal transduction in MSC, which promotes mammary tumor growth in part through secretion of the signaling protein prosaposin. On a stiff matrix, MSC cultured with conditioned media from mammary cancer cells expressed increased levels of α-smooth muscle actin, a marker of CAF, compared with MSC cultured on a soft matrix. By contrast, MSC cultured on a stiff matrix secreted prosaposin that promoted proliferation and survival of mammary carcinoma cells but inhibited metastasis. Our findings suggest that in addition to chemical stimuli, increased stiffness of the ECM in the tumor microenvironment induces differentiation of MSC to CAF, triggering enhanced proliferation and survival of mammary cancer cells. Cancer Res; 77(22); 6179-89. ©2017 AACR . ©2017 American Association for Cancer Research.
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Analytic Scattering and Refraction Models for Exoplanet Transit Spectra
NASA Astrophysics Data System (ADS)
Robinson, Tyler D.; Fortney, Jonathan J.; Hubbard, William B.
2017-12-01
Observations of exoplanet transit spectra are essential to understanding the physics and chemistry of distant worlds. The effects of opacity sources and many physical processes combine to set the shape of a transit spectrum. Two such key processes—refraction and cloud and/or haze forward-scattering—have seen substantial recent study. However, models of these processes are typically complex, which prevents their incorporation into observational analyses and standard transit spectrum tools. In this work, we develop analytic expressions that allow for the efficient parameterization of forward-scattering and refraction effects in transit spectra. We derive an effective slant optical depth that includes a correction for forward-scattered light, and present an analytic form of this correction. We validate our correction against a full-physics transit spectrum model that includes scattering, and we explore the extent to which the omission of forward-scattering effects may bias models. Also, we verify a common analytic expression for the location of a refractive boundary, which we express in terms of the maximum pressure probed in a transit spectrum. This expression is designed to be easily incorporated into existing tools, and we discuss how the detection of a refractive boundary could help indicate the background atmospheric composition by constraining the bulk refractivity of the atmosphere. Finally, we show that opacity from Rayleigh scattering and collision-induced absorption will outweigh the effects of refraction for Jupiter-like atmospheres whose equilibrium temperatures are above 400-500 K.
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Reichardt, J; Hess, M; Macke, A
2000-04-20
Multiple-scattering correction factors for cirrus particle extinction coefficients measured with Raman and high spectral resolution lidars are calculated with a radiative-transfer model. Cirrus particle-ensemble phase functions are computed from single-crystal phase functions derived in a geometrical-optics approximation. Seven crystal types are considered. In cirrus clouds with height-independent particle extinction coefficients the general pattern of the multiple-scattering parameters has a steep onset at cloud base with values of 0.5-0.7 followed by a gradual and monotonic decrease to 0.1-0.2 at cloud top. The larger the scattering particles are, the more gradual is the rate of decrease. Multiple-scattering parameters of complex crystals and of imperfect hexagonal columns and plates can be well approximated by those of projected-area equivalent ice spheres, whereas perfect hexagonal crystals show values as much as 70% higher than those of spheres. The dependencies of the multiple-scattering parameters on cirrus particle spectrum, base height, and geometric depth and on the lidar parameters laser wavelength and receiver field of view, are discussed, and a set of multiple-scattering parameter profiles for the correction of extinction measurements in homogeneous cirrus is provided.
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Dispersive approach to two-photon exchange in elastic electron-proton scattering
Blunden, P. G.; Melnitchouk, W.
2017-06-14
We examine the two-photon exchange corrections to elastic electron-nucleon scattering within a dispersive approach, including contributions from both nucleon and Δ intermediate states. The dispersive analysis avoids off-shell uncertainties inherent in traditional approaches based on direct evaluation of loop diagrams, and guarantees the correct unitary behavior in the high energy limit. Using empirical information on the electromagnetic nucleon elastic and NΔ transition form factors, we compute the two-photon exchange corrections both algebraically and numerically. Finally, results are compared with recent measurements of e + p to e - p cross section ratios from the CLAS, VEPP-3 and OLYMPUS experiments.
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Titus, L. J.; Nunes, Filomena M.
2014-03-12
Here, the effects of non-local potentials have historically been approximately included by applying a correction factor to the solution of the corresponding equation for the local equivalent interaction. This is usually referred to as the Perey correction factor. In this work we investigate the validity of the Perey correction factor for single-channel bound and scattering states, as well as in transfer (p, d) cross sections. Method: We solve the scattering and bound state equations for non-local interactions of the Perey-Buck type, through an iterative method. Using the distorted wave Born approximation, we construct the T-matrix for (p,d) on 17O, 41Ca,more » 49Ca, 127Sn, 133Sn, and 209Pb at 20 and 50 MeV. As a result, we found that for bound states, the Perey corrected wave function resulting from the local equation agreed well with that from the non-local equation in the interior region, but discrepancies were found in the surface and peripheral regions. Overall, the Perey correction factor was adequate for scattering states, with the exception of a few partial waves corresponding to the grazing impact parameters. These differences proved to be important for transfer reactions. In conclusion, the Perey correction factor does offer an improvement over taking a direct local equivalent solution. However, if the desired accuracy is to be better than 10%, the exact solution of the non-local equation should be pursued.« less
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NASA Astrophysics Data System (ADS)
Holmes, Timothy W.
2001-01-01
A detailed tomotherapy inverse treatment planning method is described which incorporates leakage and head scatter corrections during each iteration of the optimization process, allowing these effects to be directly accounted for in the optimized dose distribution. It is shown that the conventional inverse planning method for optimizing incident intensity can be extended to include a `concurrent' leaf sequencing operation from which the leakage and head scatter corrections are determined. The method is demonstrated using the steepest-descent optimization technique with constant step size and a least-squared error objective. The method was implemented using the MATLAB scientific programming environment and its feasibility demonstrated for 2D test cases simulating treatment delivery using a single coplanar rotation. The results indicate that this modification does not significantly affect convergence of the intensity optimization method when exposure times of individual leaves are stratified to a large number of levels (>100) during leaf sequencing. In general, the addition of aperture dependent corrections, especially `head scatter', reduces incident fluence in local regions of the modulated fan beam, resulting in increased exposure times for individual collimator leaves. These local variations can result in 5% or greater local variation in the optimized dose distribution compared to the uncorrected case. The overall efficiency of the modified intensity optimization algorithm is comparable to that of the original unmodified case.
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Nanotechnology for mesenchymal stem cell therapies.
Corradetti, Bruna; Ferrari, Mauro
2016-10-28
Mesenchymal stem cells (MSC) display great proliferative, differentiative, chemotactic, and immune-modulatory properties required to promote tissue repair. Several clinical trials based on the use of MSC are currently underway for therapeutic purposes. The aim of this article is to examine the current trends and potential impact of nanotechnology in MSC-driven regenerative medicine. Nanoparticle-based approaches are used as powerful carrier systems for the targeted delivery of bioactive molecules to ensure MSC long-term maintenance in vitro and to enhance their regenerative potential. Nanostructured materials have been developed to recapitulate the stem cell niche within a tissue and to instruct MSC toward the creation of regeneration-permissive environment. Finally, the capability of MSC to migrate toward the site of injury/inflammation has allowed for the development of diagnostic imaging systems able to monitor transplanted stem cell bio-distribution, toxicity, and therapeutic effectiveness. Copyright © 2015 Elsevier B.V. All rights reserved.
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Role of aryl hydrocarbon receptor in mesenchymal stromal cell activation: A minireview.
de Almeida, Danilo Candido; Evangelista, Laura Sibele Martins; Câmara, Niels Olsen Saraiva
2017-09-26
Mesenchymal stromal cells (MSCs) possess great therapeutic advantages due to their ability to produce a diverse array of trophic/growth factors related to cytoprotection and immunoregulation. MSC activation via specific receptors is a crucial event for these cells to exert their immunosuppressive response. The aryl-hydrocarbon receptor (AhR) is a sensitive molecule for external signals and it is expressed in MSCs and, upon positive activation, may potentially regulate the MSC-associated immunomodulatory function. Consequently, signalling pathways linked to AhR activation can elucidate some of the molecular cascades involved in MSC-mediated immunosuppression. In this minireview, we have noted some important findings concerning MSC regulation via AhR, highlighting that its activation is associated with improvement in migration and immunoregulation, as well as an increase in pro-regenerative potential. Thus, AhR-mediated MSC activation can contribute to new perspectives on MSC-based therapies, particularly those directed at immune-associated disorders.
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Kay, Alasdair Gawain; Dale, Tina Patricia; Akram, Khondoker Mehedi; Mohan, Param; Hampson, Karen; Maffulli, Nicola; Spiteri, Monica A; El Haj, Alicia Jennifer; Forsyth, Nicholas Robert
2015-01-01
Human mesenchymal stem cells (hMSC) are multipotent progenitor cells. We propose the optimization of hMSC isolation and recovery using the application of a controlled hypoxic environment. We evaluated oxygen, glucose and serum in the recovery of hMSC from bone marrow (BMhMSC). Colony forming units-fibroblastic, cell numbers, tri-lineage differentiation, immunofluorescence and microarray were used to confirm and characterize BMhMSC. In an optimized (2% O(2), 4.5 g/l glucose and 5% serum) environment both colony forming units-fibroblastic (p = 0.01) and cell numbers (p = 0.0001) were enhanced over standard conditions. Transcriptional analysis identified differential expression of bone morphogenetic protein 2 (BMP2) and, putatively, chemokine (C-X-C motif) receptor 2 (CXCR2) signaling pathways. We have detailed a potential milestone in the process of refinement of the BMhMSC isolation process.
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Lignin-rich biomass of cotton by-products for biorefineries via pyrolysis.
Chen, Jiao; Liang, Jiajin; Wu, Shubin
2016-10-01
Pyrolysis was demonstrated to investigate the thermal decomposition characteristics and potential of lignin-rich cotton by-products cotton exocarp (CE) and spent mushroom substrate consisted of cotton by-products (MSC) for biorefineries. The chemical component and structure alteration of CE and MSC was found to affect their thermochemical behaviors. The bio-oil yield from CE was 58.13wt% while the maximum yield from MSC was 45.01% at 600°C. The phenolic compounds obtained from CE and MSC were 33.9% and 39.2%, respectively. The yield of acetic acid from MSC between 400 and 600°C was about 30-38% lower than that from CE, which suggests the high quality of bio-oil was obtained. Biochar from MSC via slow pyrolysis had a high mass yield (44.38wt%) with well-developed pore structure. Copyright © 2016 Elsevier Ltd. All rights reserved.
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Agonism of Wnt/β-catenin signaling promotes mesenchymal stem cell (MSC) expansion
Hoffman, Michael D.; Benoit, Danielle S.W.
2014-01-01
Promoting mesenchymal stem cell (MSC) proliferation has numerous applications in stem cell therapies, particularly in the area of regenerative medicine. In order for cell-based regenerative approaches to be realized, MSC proliferation must be achieved in a controlled manner without compromising stem cell differentiation capacities. Here we demonstrate that 6-bromoindirubin-3’-oxime (BIO) increases MSC β-catenin activity 106-fold and stem cell-associated gene expression ~33-fold respectively over untreated controls. Subsequently, BIO treatment increases MSC populations 1.8-fold in typical 2D culture conditions, as well as 1.3-fold when encapsulated within hydrogels compared to untreated cells. Furthermore, we demonstrate that BIO treatment does not reduce MSC multipotency, where MSCs maintain their ability to differentiate into osteoblasts, chondrocytes, and adipocytes using standard conditions. Taken together, our results demonstrate BIOs potential utility as a proliferative agent for cell transplantation and tissue regeneration. PMID:23554411
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[Mesenchymal stem/stroma cells : Therapeutic potential in the treatment of autoimmune diseases].
Schäfer, R; Daikeler, T
2016-10-01
Mesenchymal stem and stromal cells (MSC) are propagated for the treatment of autoimmune and autoinflammatory processes. These cells can be relatively easily obtained from various tissues. The MSC feature anti-inflammatory and immunosuppressive properties in vitro as well as in animal models. Initial reports on the clinical application of MSC for various diseases are available, some with promising results and so far no reported toxicity; however, data from phase III studies are still lacking and crucial questions are still unanswered. The MSC preparations used are heterogeneous and also differ depending on the source and it is unclear whether autologous (own) or allogeneic (foreign) MSC are more suitable for therapeutic use. Long-term consequences, such as possible malignant transformation and possible endogenous tumor growth stimulation cannot be completely excluded. Ultimately, these questions can only be answered through randomized controlled trials for defined clinical indications with defined MSC.
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Norman, Christel; Liu, Zhen-Wei; Rigby, Paul; Raso, Albert; Petrov, Yevgeniy; Martinac, Boris
2005-07-01
The mechanosensitive channel of large conductance (MscL) plays an important role in the survival of bacterial cells to hypo-osmotic shock. This channel has been extensively studied and its sequence, structure and electrophysiological characteristics are well known. Here we present a method to visualise MscL in living bacteria using confocal microscopy. By creating a gene fusion between mscl and the gene encoding the green fluorescent protein (GFP) we were able to express the fusion protein MscL-GFP in bacteria. We show that MscL-GFP is present in the cytoplasmic membrane and forms functional channels. These channels have the same characteristics as wild-type MscL, except that they require more pressure to open. This method could prove an interesting, non-invasive, tool to study the localisation and the regulation of expression of MscL in bacteria.
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Spectral structure of laser light scattering revisited: bandwidths of nonresonant scattering lidars.
She, C Y
2001-09-20
It is well known that scattering lidars, i.e., Mie, aerosol-wind, Rayleigh, high-spectral-resolution, molecular-wind, rotational Raman, and vibrational Raman lidars, are workhorses for probing atmospheric properties, including the backscatter ratio, aerosol extinction coefficient, temperature, pressure, density, and winds. The spectral structure of molecular scattering (strength and bandwidth) and its constituent spectra associated with Rayleigh and vibrational Raman scattering are reviewed. Revisiting the correct name by distinguishing Cabannes scattering from Rayleigh scattering, and sharpening the definition of each scattering component in the Rayleigh scattering spectrum, the review allows a systematic, logical, and useful comparison in strength and bandwidth between each scattering component and in receiver bandwidths (for both nighttime and daytime operation) between the various scattering lidars for atmospheric sensing.
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Implementation of an Analytical Raman Scattering Correction for Satellite Ocean-Color Processing
NASA Technical Reports Server (NTRS)
McKinna, Lachlan I. W.; Werdell, P. Jeremy; Proctor, Christopher W.
2016-01-01
Raman scattering of photons by seawater molecules is an inelastic scattering process. This effect can contribute significantly to the water-leaving radiance signal observed by space-borne ocean-color spectroradiometers. If not accounted for during ocean-color processing, Raman scattering can cause biases in derived inherent optical properties (IOPs). Here we describe a Raman scattering correction (RSC) algorithm that has been integrated within NASA's standard ocean-color processing software. We tested the RSC with NASA's Generalized Inherent Optical Properties algorithm (GIOP). A comparison between derived IOPs and in situ data revealed that the magnitude of the derived backscattering coefficient and the phytoplankton absorption coefficient were reduced when the RSC was applied, whilst the absorption coefficient of colored dissolved and detrital matter remained unchanged. Importantly, our results show that the RSC did not degrade the retrieval skill of the GIOP. In addition, a timeseries study of oligotrophic waters near Bermuda showed that the RSC did not introduce unwanted temporal trends or artifacts into derived IOPs.
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The mechanoelectrical response of the cytoplasmic membrane of Vibrio cholerae.
Rowe, Ian; Elahi, Merina; Huq, Anwar; Sukharev, Sergei
2013-07-01
Persistence of Vibrio cholerae in waters of fluctuating salinity relies on the capacity of this facultative enteric pathogen to adapt to varying osmotic conditions. In an event of osmotic downshift, osmolytes accumulated inside the bacterium can be quickly released through tension-activated channels. With the newly established procedure of giant spheroplast preparation from V. cholerae, we performed the first patch-clamp characterization of its cytoplasmic membrane and compared tension-activated currents with those in Esherichia coli. Saturating pressure ramps revealed two waves of activation belonging to the ∼1-nS mechanosensitive channel of small conductance (MscS)-like channels and ∼3-nS mechanosensitive channel of large conductance (MscL)-like channels, with a pressure midpoint ratio p0.5MscS/p0.5MscL of 0.48. We found that MscL-like channels in V. cholerae present at a density three times higher than in E. coli, and yet, these vibrios were less tolerant to large osmotic downshocks. The Vibrio MscS-like channels exhibit characteristic inward rectification and subconductive states at depolarizing voltages; they also adapt and inactivate at subsaturating tensions and recover within 2 s upon tension release, just like E. coli MscS. Trehalose, a compatible internal osmolyte accumulated under hypertonic conditions, significantly shifts activation curves of both MscL- and MscS-like channels toward higher tensions, yet does not freely partition into the channel pore. Direct electrophysiology of V. cholerae offers new avenues for the in situ analysis of membrane components critical for osmotic survival and electrogenic transport in this pathogen.
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The mechanoelectrical response of the cytoplasmic membrane of Vibrio cholerae
Rowe, Ian; Elahi, Merina; Huq, Anwar
2013-01-01
Persistence of Vibrio cholerae in waters of fluctuating salinity relies on the capacity of this facultative enteric pathogen to adapt to varying osmotic conditions. In an event of osmotic downshift, osmolytes accumulated inside the bacterium can be quickly released through tension-activated channels. With the newly established procedure of giant spheroplast preparation from V. cholerae, we performed the first patch-clamp characterization of its cytoplasmic membrane and compared tension-activated currents with those in Esherichia coli. Saturating pressure ramps revealed two waves of activation belonging to the ∼1-nS mechanosensitive channel of small conductance (MscS)-like channels and ∼3-nS mechanosensitive channel of large conductance (MscL)-like channels, with a pressure midpoint ratio p0.5MscS/p0.5MscL of 0.48. We found that MscL-like channels in V. cholerae present at a density three times higher than in E. coli, and yet, these vibrios were less tolerant to large osmotic downshocks. The Vibrio MscS-like channels exhibit characteristic inward rectification and subconductive states at depolarizing voltages; they also adapt and inactivate at subsaturating tensions and recover within 2 s upon tension release, just like E. coli MscS. Trehalose, a compatible internal osmolyte accumulated under hypertonic conditions, significantly shifts activation curves of both MscL- and MscS-like channels toward higher tensions, yet does not freely partition into the channel pore. Direct electrophysiology of V. cholerae offers new avenues for the in situ analysis of membrane components critical for osmotic survival and electrogenic transport in this pathogen. PMID:23797422
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Hertegård, S; Cedervall, J; Svensson, B; Forsberg, K; Maurer, F H J; Vidovska, D; Olivius, P; Ahrlund-Richter, L; Le Blanc, K
2006-07-01
The aim of this study was to analyze the short-term viscoelastic and histologic properties of scarred rabbit vocal folds after injection of human mesenchymal stem cells (MSC) as well as the degree of MSC survival. Because MSCs are antiinflammatory and regenerate mesenchymal tissues, can MSC injection reduce vocal fold scarring after injury? Twelve vocal folds from 10 New Zealand rabbits were scarred by a localized resection and injected with human MSC or saline. Eight vocal folds were left as controls. After 4 weeks, 10 larynges were stained for histology and evaluation of the lamina propria thickness. Collagen type I content was analyzed from six rabbits. MSC survival was analyzed by fluorescent in situ hybridization staining from three rabbits. Viscoelasticity for 10 vocal folds was analyzed in a parallel-plate rheometer. The rheometry on fresh-frozen samples showed decreased dynamic viscosity and lower elastic modulus (P<.01) in the scarred samples injected with MSC as compared with the untreated scarred group. Normal controls had lower dynamic viscosity and elastic modulus as compared with the scarred untreated and treated vocal folds (P<.01). Histologic analysis showed a higher content of collagen type 1 in the scarred samples as compared with the normal vocal folds and with the scarred folds treated with MSC. MSCs remained in all samples analyzed. The treated scarred vocal folds showed persistent MSC. Injection of scarred rabbit vocal folds with MSC rendered improved viscoelastic parameters and less signs of scarring expressed as collagen content in comparison to the untreated scarred vocal folds.
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Comparative effects of mesenchymal stem cell therapy in distinct stages of chronic renal failure.
Caldas, Heloisa Cristina; de Paula Couto, Thaís Amarante Peres; Fernandes, Ida Maria Maximina; Baptista, Maria Alice Sperto Ferreira; Kawasaki-Oyama, Rosa Sayoko; Goloni-Bertollo, Eny Maria; Braile, Domingo Marcolino; Abbud-Filho, Mario
2015-10-01
The therapeutic potential of adult stem cells in the treatment of chronic diseases is becoming increasingly evident. In the present study, we sought to assess whether treatment with mesenchymal stem cells (MSCs) efficiently retards progression of chronic renal failure (CRF) when administered to experimental models of less severe CRF. We used two renal mass reduction models to simulate different stages of CRF (5/6 or 2/3 mass renal reduction). Renal functional parameters measured were serum creatinine (SCr), creatinine clearance (CCr), rate of decline in CCr (RCCr), and 24-h proteinuria (PT24h). We also evaluated renal morphology by histology and immunohistochemistry. MSCs were obtained from bone marrow aspirates and injected into the renal parenchyma of the remnant kidneys of both groups of rats with CRF (MSC5/6 or MSC2/3). Animals from groups MSC5/6 and CRF2/3 seemed to benefit from MSC therapy because they showed significantly reduction in SCr and PT24h, increase in CCr and slowed the RCCr after 90 days. Treatment reduced glomerulosclerosis but significant improvement did occur in the tubulointerstitial compartment with much less fibrosis and atrophy. MSC therapy reduced inflammation by decreasing macrophage accumulation proliferative activity (PCNA-positive cells) and fibrosis (α-SM-actin). Comparisons of renal functional and morphological parameters responses between the two groups showed that rats MSC2/3 were more responsive to MSC therapy than MSC5/6. This study showed that MSC therapy is efficient to retard CRF progression and might be more effective when administered during less severe stages of CRF.
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Therapeutic Potential of Mesenchymal Stem Cell-Derived Exosomes in the Treatment of Eye Diseases.
Harrell, C Randall; Simovic Markovic, Bojana; Fellabaum, Crissy; Arsenijevic, Aleksandar; Djonov, Valentin; Arsenijevic, Nebojsa; Volarevic, Vladislav
2018-05-18
Mesenchymal stem cells (MSCs) were, due to their immunomodulatory and pro-angiogenic characteristics, extensively explored as new therapeutic agents in cell-based therapy of uveitis, glaucoma, retinal and ocular surface diseases.Since it was recently revealed that exosomes play an important role in biological functions of MSCs, herewith we summarized current knowledge about the morphology, structure, phenotype and functional characteristics of MSC-derived exosomes emphasizing their therapeutic potential in the treatment of eye diseases.MSC-derived exosomes were as efficient as transplanted MSCs in limiting the extent of eye injury and inflammation. Immediately after intravitreal injection, MSC-derived exosomes, due to nano-dimension, diffused rapidly throughout the retina and significantly attenuated retinal damage and inflammation. MSC-derived exosomes successfully delivered trophic and immunomodulatory factors to the inner retina and efficiently promoted survival and neuritogenesis of injured retinal ganglion cells. MSC-derived exosomes efficiently suppressed migration of inflammatory cells, attenuated detrimental Th1 and Th17 cell-driven immune response and ameliorated experimental autoimmune uveitis. MSC-derived exosomes were able to fuse with the lysosomes within corneal cells, enabling delivering of MSC-derived active β-glucuronidase and consequent catabolism of accumulated glycosaminoglycans, indicating their therapeutic potential in the treatment of Mucopolysaccharidosis VII (Sly Syndrome). Importantly, beneficent effects were noticed only in animals that received MSC-derived exosomes and were not seen after therapy with fibroblasts-derived exosomes confirming specific therapeutic potential of MSCs and their products in the treatment of eye diseases.In conclusion, MSC-derived exosomes represent potentially new therapeutic agents in the therapy of degenerative and inflammatory ocular diseases.
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BLDG. 29 - INTERIOR (CLOSEUP) - GONDOLA - MSC
1966-01-01
The new centrifuge at MSC, located in the Flight Acceleration Facility (FAF), Bldg. 29. The 50-ft. arm can swing the 3-man gondola to create G-Forces Astronauts will experience during liftoffs and re-entry conditions. MSC, HOUSTON, TX CN
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A curvature-corrected Kirchhoff formulation for radar sea-return from the near vertical
NASA Technical Reports Server (NTRS)
Jackson, F. C.
1974-01-01
A new theoretical treatment of the problem of electromagnetic wave scattering from a randomly rough surface is given. A high frequency correction to the Kirchhoff approximation is derived from a field integral equation for a perfectly conducting surface. The correction, which accounts for the effect of local surface curvature, is seen to be identical with an asymptotic form found by Fock (1945) for diffraction by a paraboloid. The corrected boundary values are substituted into the far field Stratton-Chu integral, and average backscattered powers are computed assuming the scattering surface is a homogeneous Gaussian process. Preliminary calculations for K(-4) ocean wave spectrum indicate a resonable modelling of polarization effects near the vertical, theta 45 deg. Correspondence with the results of small perturbation theory is shown.
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NASA Technical Reports Server (NTRS)
Williams, F. E.; Price, J. B.; Lemon, R. S.
1972-01-01
The simulation developments for use in dynamics and control analysis during boost from liftoff to orbit insertion are reported. Also included are wind response studies of the NR-GD 161B/B9T delta wing booster/delta wing orbiter configuration, the MSC 036B/280 inch solid rocket motor configuration, the MSC 040A/L0X-propane liquid injection TVC configuration, the MSC 040C/dual solid rocket motor configuration, and the MSC 049/solid rocket motor configuration. All of the latest math models (rigid and flexible body) developed for the MSC/GD Space Shuttle Functional Simulator, are included.
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Long, Teng; Zhu, Zhenan; Awad, Hani A.; Schwarz, Edward M.; Hilton, Matthew J.; Dong, Yufeng
2014-01-01
Structural bone allografts are widely used in the clinic to treat critical sized bone defects, despite lacking the osteoinductive characteristics of live autografts. To address this, we generated revitalized structural allografts wrapped with mesenchymal stem/progenitor cell (MSC) sheets, which were produced by expanding primary syngenic bone marrow derived cells on temperature-responsive plates, as a tissue engineered periosteum. In vitro assays demonstrated maintenance of the MSC phenotype in the sheets, suggesting that short-term culturing of MSC sheets is not detrimental. To test their efficacy in vivo, allografts wrapped with MSC sheets were transplanted into 4-mm murine femoral defects and compared to allografts with direct seeding of MSCs and allografts without cells. Evaluations consisted of x-ray plain radiography, 3D microCT, histology, and biomechanical testing at 4- and 6-weeks post-surgery. Our findings demonstrate that MSC sheets induce prolonged cartilage formation at the graft-host junction and enhanced bone callus formation, as well as graft-host osteointegration. Moreover, a large periosteal callus was observed spanning the allografts with MSC sheets, which partially mimics live autograft healing. Finally, biomechanical testing showed a significant increase in the structural and functional properties of MSC sheet grafted femurs. Taken together, MSC sheets exhibit enhanced osteogenicity during critical sized bone defect repair, demonstrating the feasibility of this tissue engineering solution for massive allograft healing. PMID:24393269
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Interannual variability in stratiform cloudiness and sea surface temperature
NASA Technical Reports Server (NTRS)
Norris, Joel R.; Leovy, Conway B.
1994-01-01
Marine stratiform cloudiness (MSC)(stratus, stratocumulus, and fog) is widespread over subtropical oceans west of the continents and over midlatitude oceans during summer, the season when MSC has maximum influence on surface downward radiation and is most influenced by boundary-layer processes. Long-term datasets of cloudiness and sea surface teperature (SST) from surface observations from 1952 to 1981 are used to examine interannual variations in MSC and SST. Linear correlations of anomalies in seasonal MSC amount with seasonal SST anomalies are negative and significant in midlatitude and eastern subtropical oceans, especially during summer. Significant negative correlations between SST and nimbostratus and nonprecipitating midlevel cloudiness are also observed at midlatitudes during summer, suggesting that summer storm tracks shift from year to year following year-to-year meridional shifts in the SST gradient. Over the 30-yr period, there are significant upward trends in MSC amount over the northern midlatitude oceans and a significant downward trend off the coast of California. The highest correlations and trends occur where gradients in MSC and SST are strongest. During summer, correlations between SST and MSC anomalies peak at zero lag in midlatitudes where warm advection prevails, but SST lags MSC in subtropical regions where cold advection predominates. This difference is attributed to a tendency for anomalies in latent heat flux to compensate anomalies in surface downward radiation in warm advection regions but not in cold advection regions.
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Bader, Peter; Kuçi, Zyrafete; Bakhtiar, Shahrzad; Basu, Oliver; Bug, Gesine; Dennis, Michael; Greil, Johann; Barta, Aniko; Kállay, Krisztián M; Lang, Peter; Lucchini, Giovanna; Pol, Raj; Schulz, Ansgar; Sykora, Karl-Walter; von Luettichau, Irene; Herter-Sprie, Grit; Uddin, Mohammad Ashab; Jenkin, Phil; Alsultan, Abdulrahman; Buechner, Jochen; Stein, Jerry; Kelemen, Agnes; Jarisch, Andrea; Soerensen, Jan; Salzmann-Manrique, Emilia; Hutter, Martin; Schäfer, Richard; Seifried, Erhard; Klingebiel, Thomas; Bonig, Halvard; Kuçi, Selim
2018-01-29
The inability to generate mesenchymal stromal cells (MSCs) of consistent potency likely is responsible for inconsistent clinical outcomes of patients with aGvHD receiving MSC products. We developed a novel MSC manufacturing protocol characterized by high in vitro potency and near-identity of individual doses, referred to as "MSC-Frankfurt am Main (MSC-FFM)". Herein, we report outcomes of the 69 patients who have received MSC-FFM. These were 51 children and 18 adults with refractory aGvHD grade II (4%), III (36%) or IV (59%). Patients were refractory either to frontline therapy (steroids) (29%) or to steroids and 1-5 additional lines of immunosuppressants (71%) were given infusions in four weekly intervals. The day 28 overall response rate was 83%; at the last follow-up, 61% and 25% of patients were in complete or partial remission. The median follow-up was 8.1 months. Six-month estimate for cumulative incidence of non-relapse mortality was 27% (range, 16-38); leukemia relapse mortality was 2% (range, 0-5). This was associated with a superior six-month overall survival (OS) probability rate of 71% (range, 61-83), compared to the outcome of patients not treated with MSC-FFM. This novel product was effective in children and adults, suggesting that MSC-FFM represents a promising therapy for steroid refractory aGvHD.
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Mesenchymal stem cell sheets exert anti-stenotic effects in a rat arterial injury model.
Homma, Jun; Sekine, Hidekazu; Matsuura, Katsuhisa; Kobayashi, Eiji; Shimizu, Tatsuya
2018-05-04
Restenosis after catheter or surgical intervention substantially affects the prognosis of arterial occlusive disease. Mesenchymal stem cells (MSCs) may have anti-stenotic effects on injured arteries. MSC transplantation from the adventitial side of an artery is safer than endovascular transplantation but has not been extensively examined. In this study, a rat model of femoral artery injury was used to compare the anti-stenotic effects of transplanted cell sheets and transplanted cell suspensions. Rat adipose-derived stem cells (ASCs) were used as the source of MSCs. For both cell sheets and suspensions, 6×106 MSCs were transplanted on the day of arterial injury. MSC sheets attenuated neointimal hyperplasia more than MSC suspensions (intima-to-media ratio in haematoxylin/eosin-stained sections: 0.55±0.13 vs. 1.14±0.12; P<0.05). Cell engraftment (assessed by immunohistochemistry or bioluminescence imaging of luciferase-expressing cells), arterial re-endothelialisation (evaluated by immunohistochemical staining for rat endothelial cell antigen-1) and restriction of vascular smooth muscle cell proliferation in the neointima (double-staining of alpha-smooth muscle actin and phospho-histone H3) were greater when MSC sheets were applied than when MSC suspensions were used. In conclusion, MSC sheets exhibited better anti-stenotic and cell engraftment properties than MSC suspensions. MSC sheet transplantation from the adventitial side is a promising therapy for prevention of arterial restenosis.
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Characterization of bone marrow mesenchymal stromal cells in aplastic anaemia.
Hamzic, Edita; Whiting, Karen; Gordon Smith, Edward; Pettengell, Ruth
2015-06-01
In aplastic anaemia (AA), haemopoietic activity is significantly reduced and generally attributed to failure of haemopoietic stem cells (HSC) within the bone marrow (BM). The regulation of haemopoiesis depends on the interaction between HSC and various cells of the BM microenvironment, including mesenchymal stromal cells (MSC). MSC involvement in the functional restriction of HSC in AA is largely unknown and therefore, the physical and functional properties of AA MSC were studied in vitro. MSC were characterized by their phenotype and ability to form adherent stromal layers. The functional properties of AA MSC were assessed through proliferative, clonogenic and cross-over culture assays. Results indicate that although AA MSC presented typical morphology and distinctive mesenchymal markers, stromal formation was reduced, with 50% of BM samples failing to produce adherent layers. Furthermore, their proliferative and clonogenic capacity was markedly decreased (P = 0·03 and P = 0·04 respectively) and the ability to sustain haemopoiesis was significantly reduced, as assessed by total cell proliferation (P = 0·032 and P = 0·019 at Week 5 and 6, respectively) and clonogenic potential of HSC (P = 0·02 at Week 6). It was concluded that the biological characteristics of AA MSC are different from those of control MSC and their in vitro haemopoiesis-supporting ability is significantly reduced. © 2015 John Wiley & Sons Ltd.
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Succar, Peter; Medynskyj, Michael; Breen, Edmond J.; Batterham, Tony; Molloy, Mark P.; Herbert, Benjamin R.
2016-01-01
Background. Biological therapeutics such as adipose-derived mesenchymal stem cell (MSC) therapy are gaining acceptance for knee-osteoarthritis (OA) treatment. Reports of OA-patients show reductions in cartilage defects and regeneration of hyaline-like-cartilage with MSC-therapy. Suspending MSCs in hyaluronan commonly occurs in animals and humans, usually without supporting data. Objective. To elucidate the effects of different concentrations of hyaluronan on MSC growth kinetics. Methods. Using a range of hyaluronan concentrations, we measured MSC adherence and proliferation on culture plastic surfaces and a novel cartilage-adhesion assay. We employed time-course and dispersion imaging to assess MSC binding to cartilage. Cytokine profiling was also conducted on the MSC-secretome. Results. Hyaluronan had dose-dependent effects on growth kinetics of MSCs at concentrations of entanglement point (1 mg/mL). At higher concentrations, viscosity effects outweighed benefits of additional hyaluronan. The cartilage-adhesion assay highlighted for the first time that hyaluronan-primed MSCs increased cell attachment to cartilage whilst the presence of hyaluronan did not. Our time-course suggested patients undergoing MSC-therapy for OA could benefit from joint-immobilisation for up to 8 hours. Hyaluronan also greatly affected dispersion of MSCs on cartilage. Conclusion. Our results should be considered in future trials with MSC-therapy using hyaluronan as a vehicle, for the treatment of OA. PMID:26981136
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Wen, Sicheng; Dooner, Mark; Cheng, Yan; Papa, Elaine; Del Tatto, Michael; Pereira, Mandy; Deng, Yanhui; Goldberg, Laura; Aliotta, Jason; Chatterjee, Devasis; Stewart, Connor; Carpanetto, Andrea; Collino, Federica; Bruno, Stefania; Camussi, Giovanni; Quesenberry, Peter
2016-01-01
Mesenchymal stromal cells (MSC) have been shown to reverse radiation damage to marrow stem cells. We have evaluated the capacity of MSC-derived extracellular vesicles (MSC-EVs) to mitigate radiation injury to marrow stem cells at 4 hours to 7 days after irradiation. Significant restoration of marrow stem cell engraftment at 4, 24 and 168 hours post-irradiation by exposure to MSC-EVs was observed at 3 weeks to 9 months after transplant and further confirmed by secondary engraftment. Intravenous injection of MSC-EVs to 500cGy exposed mice led to partial recovery of peripheral blood counts and restoration of the engraftment of marrow. The murine hematopoietic cell line, FDC-P1 exposed to 500 cGy, showed reversal of growth inhibition, DNA damage and apoptosis on exposure to murine or human MSC-EVs. Both murine and human MSC-EVs reverse radiation damage to murine marrow cells and stimulate normal murine marrow stem cell/progenitors to proliferate. A preparation with both exosomes and microvesicles was found to be superior to either microvesicles or exosomes alone. Biologic activity was seen in freshly isolated vesicles and in vesicles stored for up to 6 months in 10% DMSO at −80°C. These studies indicate that MSC-EVs can reverse radiation damage to bone marrow stem cells. PMID:27150009
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Du, Hui-Cong; Jiang, Lin; Geng, Wen-Xin; Li, Jing; Zhang, Rui; Dang, Jin-Ge; Shu, Mao-Guo; Li, Li-Wen
2017-01-01
MSC treatment can promote cutaneous wound repair through multiple mechanisms, and paracrine mediators secreted by MSC are responsible for most of its therapeutic benefits. Recently, MSC sheet composed of live MSCs and their secreted ECMs was reported to promote wound healing; however, whether its ECM alone could accelerate wound closure remained unknown. In this study, Nc-ECM and Cc-ECM were prepared from nonconditioned and CoCl 2 -conditioned MSC sheets, respectively, and their wound healing properties were evaluated in a mouse model of full-thickness skin defect. Our results showed that Nc-ECM can significantly promote wound repair through early adipocyte recruitment, rapid reepithelialization, enhanced granulation tissue growth, and augmented angiogenesis. Moreover, conditioning of MSC sheet with CoCl 2 dramatically enriched its ECM with collagen I, collagen III, TGF- β 1, VEGF, and bFGF via activation of HIF-1 α and hence remarkably improved its ECM's in vivo wound healing potency. All the Cc-ECM-treated wounds completely healed on day 7, while Nc-ECM-treated wounds healed about 85.0% ± 8.6%, and no-treatment wounds only healed 69.8% ± 9.6% ( p < 0.05). Therefore, we believe that such growth factor-reinforced ECM fabricated from chemically hypoxic MSC sheet has the potential for clinical translation and will lead to a MSC-derived, cost-effective, bankable biomaterial for wound management.
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Uklejewski, Ryszard; Rogala, Piotr; Winiecki, Mariusz; Tokłowicz, Renata; Ruszkowski, Piotr; Wołuń-Cholewa, Maria
2016-06-29
We present here-designed, manufactured, and tested by our research team-the Ti-alloy prototype of the multispiked connecting scaffold (MSC-Scaffold) interfacing the components of resurfacing arthroplasty (RA) endoprostheses with bone. The spikes of the MSC-Scaffold prototype mimic the interdigitations of the articular subchondral bone, which is the natural biostructure interfacing the articular cartilage with the periarticular trabecular bone. To enhance the osteoinduction/osteointegration potential of the MSC-Scaffold, the attempts to modify its bone contacting surfaces by the process of electrochemical cathodic deposition of Ca-P was performed with further immersion of the MSC-Scaffold prototypes in SBF in order to transform the amorphous calcium-phosphate coating in hydroxyapatite-like (HA-like) coating. The pilot experimental study of biointegration of unmodified and Ca-P surface-modified MSC-Scaffold prototypes was conducted in an animal model (swine) and in osteoblast cell culture. On the basis of a microscope-histological method the biointegration was proven by the presence of trabeculae in the interspike spaces of the MSC-Scaffold prototype on longitudinal and cross-sections of bone-implant specimens. The percentage of trabeculae in the area between the spikes of specimen containing Ca-P surface modified scaffold prototype observed in microCT reconstructions of the explanted joints was visibly higher than in the case of unmodified MSC-Scaffold prototypes. Significantly higher Alkaline Phosphatase (ALP) activity and the cellular proliferation in the case of Ca-P-modified MSC-Scaffold pre-prototypes, in comparison with unmodified pre-prototypes, was found in osteoblast cell cultures. The obtained results of experimental implantation in an animal model and osteoblast cell culture evaluations of Ca-P surface-modified and non-modified biomimetic MSC-Scaffold prototypes for biomimetic entirely-cementless RA endoprostheses indicate the enhancement of the osteoinduction/osteointegration potential by the Ca-P surface modification of the Ti-alloy MSC-Scaffold prototype. Planned further research on the prototype of this biomimetic MSC-Scaffold for a new generation of RA endoprostheses is also given.
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Interdisciplinary MSc and Doctoral Education in Climate System Science at the University of Hamburg
NASA Astrophysics Data System (ADS)
Dilly, Oliver; Stammer, Detlef; Pfeiffer, Eva-Maria
2010-05-01
Modern education in climate system sciences is based on a number of disciplines such as meteorology, geophysics, oceanography, geosciences and also economics and social sciences. Facts across these disciplines are required to address the faced key issues related to climate change effectively. Climate experts need to have profound knowledge that can only be achieved in interdisciplinary MSc and PhD programs. In Europe, graduate students who completed a BSc degree are typically proceeding with MSc programs to increase knowledge and qualification. Afterwards, the participation in a doctoral program may follow. Many doctoral programs include courses supporting disciplinary methodological and scientific background in particular. Those courses derive either from advanced MSc programs or specific trainings. Typically, interdisciplinary exchange is difficult to achieve at any stage of disciplinary graduate programs. Recent developments showed the need to educate climate experts in interdisciplinary MSc programs in climate system sciences for both researchers and professionals outside the university. The University of Hamburg offers an interdisciplinary 2-yr MSc program in Integrated System Sciences with 120 ECTS (30 compulsory, 90 eligible) in English language. If the MSc student decides to proceed with a PhD thesis, he/she may not necessarily complete the MSc program but may start to work on a specific and disciplinary doctoral thesis for 3 years. Each doctoral student is guided by an advisory panel (AP) which meets at least bi-annually. The AP consists of a Principal Advisor, a Co-Advisor and a Chair of the panel who come from neighboring disciplines. The structured doctoral program with only 12 CPs includes interdisciplinary compulsory courses and tailor-made eligible expert courses. Summer schools and soft skill courses add to both MSc and doctoral programs. Accordingly, the new graduate school concepts in climate system sciences at the University of Hamburg supports starting with the interdisciplinary MSc program Integrated Climate System Sciences and then get in-depth disciplinary expertise during PhD studies. The completion of the total MSc curriculum may not be essential. Advantages and limitations of this concept will be discussed.
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Xin, Hongqi; Li, Yi; Liu, Zhongwu; Wang, Xinli; Shang, Xia; Cui, Yisheng; Zhang, Zheng Gang; Chopp, Michael
2013-01-01
To test, in vivo, the hypothesis that exosomes from multipotent mesenchymal stromal cells (MSCs) mediate microRNA 133b (miR-133b) transfer which promotes neurological recovery from stroke, we employed knock-in and knock-down technologies to up-regulate or down-regulate the miR-133b level in MSCs (miR-133b+MSCs or miR-133b−MSCs) and their corresponding exosomes, respectively. Rats were subjected to middle cerebral artery occlusion (MCAo) and were treated with naïve MSCs, miR-133b+MSCs, or miR-133b−MSC at one day after MCAo. Compared with controls, rats receiving naïve MSC treatment significantly improved functional recovery, and exhibited increased axonal plasticity and neurite remodeling in the ischemic boundary zone (IBZ) at day 14 after MCAo. The outcomes were significantly enhanced with miR-133b+MSC treatment, and were significantly decreased with miR-133b−MSC treatment, compared to naïve MSC treatment. The miR-133b level in exosomes collected from the cerebral spinal fluid was significantly increased after miR-133b+MSC treatment, and was significantly decreased after miR-133b−MSC treatment at day 14 after MCAo, compared to naïve MSC treatment. Tagging exosomes with green fluorescent protein demonstrated that exosomes-enriched extracellular particles were released from MSCs and transferred to adjacent astrocytes and neurons. The expression of selective targets for miR-133b, connective tissue growth factor and ras homolog gene family member A, were significantly decreased in the IBZ after miR-133b+MSC treatment, while their expression remained at similar elevated levels after miR-133b−MSC treatment, compared to naïve MSC treatment. Collectively, our data suggest that exosomes from MSCs mediate the miR-133b transfer to astrocytes and neurons, which regulate gene expression, subsequently benefit neurite remodeling and functional recovery after stroke. PMID:23630198
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Boos, Anja M; Loew, Johanna S; Deschler, Gloria; Arkudas, Andreas; Bleiziffer, Oliver; Gulle, Heinz; Dragu, Adrian; Kneser, Ulrich; Horch, Raymund E; Beier, Justus P
2011-06-01
Bone tissue engineering approaches increasingly focus on the use of mesenchymal stem cells (MSC). In most animal transplantation models MSC are isolated and expanded before auto cell transplantation which might be critical for clinical application in the future. Hence this study compares the potential of directly auto-transplanted versus in vitro expanded MSC with or without bone morphogenetic protein-2 (BMP-2) to induce bone formation in a large volume ceramic bone substitute in the sheep model. MSC were isolated from bone marrow aspirates and directly auto-transplanted or expanded in vitro and characterized using fluorescence activated cell sorting (FACS) and RT-PCR analysis before subcutaneous implantation in combination with BMP-2 and β-tricalcium phosphate/hydroxyapatite (β-TCP/HA) granules. Constructs were explanted after 1 to 12 weeks followed by histological and RT-PCR evaluation. Sheep MSC were CD29(+), CD44(+) and CD166(+) after selection by Ficoll gradient centrifugation, while directly auto-transplanted MSC-populations expressed CD29 and CD166 at lower levels. Both, directly auto-transplanted and expanded MSC, were constantly proliferating and had a decreasing apoptosis over time in vivo. Directly auto-transplanted MSC led to de novo bone formation in a heterotopic sheep model using a β-TCP/HA matrix comparable to the application of 60 μg/ml BMP-2 only or implantation of expanded MSC. Bone matrix proteins were up-regulated in constructs following direct auto-transplantation and in expanded MSC as well as in BMP-2 constructs. Up-regulation was detected using immunohistology methods and RT-PCR. Dense vascularization was demonstrated by CD31 immunohistology staining in all three groups. Ectopic bone could be generated using directly auto-transplanted or expanded MSC with β-TCP/HA granules alone. Hence BMP-2 stimulation might become dispensable in the future, thus providing an attractive, clinically feasible approach to bone tissue engineering. © 2011 The Authors Journal of Cellular and Molecular Medicine © 2011 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd.
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Uklejewski, Ryszard; Rogala, Piotr; Winiecki, Mariusz; Tokłowicz, Renata; Ruszkowski, Piotr; Wołuń-Cholewa, Maria
2016-01-01
We present here—designed, manufactured, and tested by our research team—the Ti-alloy prototype of the multispiked connecting scaffold (MSC-Scaffold) interfacing the components of resurfacing arthroplasty (RA) endoprostheses with bone. The spikes of the MSC-Scaffold prototype mimic the interdigitations of the articular subchondral bone, which is the natural biostructure interfacing the articular cartilage with the periarticular trabecular bone. To enhance the osteoinduction/osteointegration potential of the MSC-Scaffold, the attempts to modify its bone contacting surfaces by the process of electrochemical cathodic deposition of Ca-P was performed with further immersion of the MSC-Scaffold prototypes in SBF in order to transform the amorphous calcium-phosphate coating in hydroxyapatite-like (HA-like) coating. The pilot experimental study of biointegration of unmodified and Ca-P surface-modified MSC-Scaffold prototypes was conducted in an animal model (swine) and in osteoblast cell culture. On the basis of a microscope-histological method the biointegration was proven by the presence of trabeculae in the interspike spaces of the MSC-Scaffold prototype on longitudinal and cross-sections of bone-implant specimens. The percentage of trabeculae in the area between the spikes of specimen containing Ca-P surface modified scaffold prototype observed in microCT reconstructions of the explanted joints was visibly higher than in the case of unmodified MSC-Scaffold prototypes. Significantly higher Alkaline Phosphatase (ALP) activity and the cellular proliferation in the case of Ca-P-modified MSC-Scaffold pre-prototypes, in comparison with unmodified pre-prototypes, was found in osteoblast cell cultures. The obtained results of experimental implantation in an animal model and osteoblast cell culture evaluations of Ca-P surface-modified and non-modified biomimetic MSC-Scaffold prototypes for biomimetic entirely-cementless RA endoprostheses indicate the enhancement of the osteoinduction/osteointegration potential by the Ca-P surface modification of the Ti-alloy MSC-Scaffold prototype. Planned further research on the prototype of this biomimetic MSC-Scaffold for a new generation of RA endoprostheses is also given. PMID:28773652
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Benisch, Peggy; Schilling, Tatjana; Klein-Hitpass, Ludger; Frey, Sönke P.; Seefried, Lothar; Raaijmakers, Nadja; Krug, Melanie; Regensburger, Martina; Zeck, Sabine; Schinke, Thorsten; Amling, Michael; Ebert, Regina; Jakob, Franz
2012-01-01
Primary osteoporosis is an age-related disease characterized by an imbalance in bone homeostasis. While the resorptive aspect of the disease has been studied intensely, less is known about the anabolic part of the syndrome or presumptive deficiencies in bone regeneration. Multipotent mesenchymal stem cells (MSC) are the primary source of osteogenic regeneration. In the present study we aimed to unravel whether MSC biology is directly involved in the pathophysiology of the disease and therefore performed microarray analyses of hMSC of elderly patients (79–94 years old) suffering from osteoporosis (hMSC-OP). In comparison to age-matched controls we detected profound changes in the transcriptome in hMSC-OP, e.g. enhanced mRNA expression of known osteoporosis-associated genes (LRP5, RUNX2, COL1A1) and of genes involved in osteoclastogenesis (CSF1, PTH1R), but most notably of genes coding for inhibitors of WNT and BMP signaling, such as Sclerostin and MAB21L2. These candidate genes indicate intrinsic deficiencies in self-renewal and differentiation potential in osteoporotic stem cells. We also compared both hMSC-OP and non-osteoporotic hMSC-old of elderly donors to hMSC of ∼30 years younger donors and found that the transcriptional changes acquired between the sixth and the ninth decade of life differed widely between osteoporotic and non-osteoporotic stem cells. In addition, we compared the osteoporotic transcriptome to long term-cultivated, senescent hMSC and detected some signs for pre-senescence in hMSC-OP. Our results suggest that in primary osteoporosis the transcriptomes of hMSC populations show distinct signatures and little overlap with non-osteoporotic aging, although we detected some hints for senescence-associated changes. While there are remarkable inter-individual variations as expected for polygenetic diseases, we could identify many susceptibility genes for osteoporosis known from genetic studies. We also found new candidates, e.g. MAB21L2, a novel repressor of BMP-induced transcription. Such transcriptional changes may reflect epigenetic changes, which are part of a specific osteoporosis-associated aging process. PMID:23028809
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Mbaye, Moussa; Diaw, Pape Abdoulaye; Gaye-Saye, Diabou; Le Jeune, Bernard; Cavalin, Goulven; Denis, Lydie; Aaron, Jean-Jacques; Delmas, Roger; Giamarchi, Philippe
2018-03-05
Permanent online monitoring of water supply pollution by hydrocarbons is needed for various industrial plants, to serve as an alert when thresholds are exceeded. Fluorescence spectroscopy is a suitable technique for this purpose due to its sensitivity and moderate cost. However, fluorescence measurements can be disturbed by the presence of suspended organic matter, which induces beam scattering and absorption, leading to an underestimation of hydrocarbon content. To overcome this problem, we propose an original technique of fluorescence spectra correction, based on a measure of the excitation beam scattering caused by suspended organic matter on the left side of the Rayleigh scattering spectral line. This correction allowed us to obtain a statistically validated estimate of the naphthalene content (used as representative of the polyaromatic hydrocarbon contamination), regardless of the amount of suspended organic matter in the sample. Moreover, it thus becomes possible, based on this correction, to estimate the amount of suspended organic matter. By this approach, the online warning system remains operational even when suspended organic matter is present in the water supply. Copyright © 2017 Elsevier B.V. All rights reserved.
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Kittaka, Daisuke; Takase, Tadashi; Akiyama, Masayuki; Nakazawa, Yasuo; Shinozuka, Akira; Shirai, Muneaki
2011-01-01
(123)I-MIBG Heart-to-Mediastinum activity ratio (H/M) is commonly used as an indicator of relative myocardial (123)I-MIBG uptake. H/M ratios reflect myocardial sympathetic nerve function, therefore it is a useful parameter to assess regional myocardial sympathetic denervation in various cardiac diseases. However, H/M ratio values differ by site, gamma camera system, position and size of region of interest (ROI), and collimator. In addition to these factors, 529 keV scatter component may also affect (123)I-MIBG H/M ratio. In this study, we examined whether the H/M ratio shows correlation between two different gamma camera systems and that sought for H/M ratio calculation formula. Moreover, we assessed the feasibility of (123)I Dual Window (IDW) method, which is a scatter correction method, and compared H/M ratios with and without IDW method. H/M ratio displayed a good correlation between two gamma camera systems. Additionally, we were able to create a new H/M calculation formula. These results indicated that the IDW method is a useful scatter correction method for calculating (123)I-MIBG H/M ratios.
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Reciprocal space mapping and single-crystal scattering rods.
Smilgies, Detlef M; Blasini, Daniel R; Hotta, Shu; Yanagi, Hisao
2005-11-01
Reciprocal space mapping using a linear gas detector in combination with a matching Soller collimator has been applied to map scattering rods of well oriented organic microcrystals grown on a solid surface. Formulae are provided to correct image distortions in angular space and to determine the required oscillation range, in order to measure properly integrated scattering intensities.
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Quasi-elastic nuclear scattering at high energies
NASA Technical Reports Server (NTRS)
Cucinotta, Francis A.; Townsend, Lawrence W.; Wilson, John W.
1992-01-01
The quasi-elastic scattering of two nuclei is considered in the high-energy optical model. Energy loss and momentum transfer spectra for projectile ions are evaluated in terms of an inelastic multiple-scattering series corresponding to multiple knockout of target nucleons. The leading-order correction to the coherent projectile approximation is evaluated. Calculations are compared with experiments.
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Granero-Moltó, Froilán; Myers, Timothy J; Weis, Jared A; Longobardi, Lara; Li, Tieshi; Yan, Yun; Case, Natasha; Rubin, Janet; Spagnoli, Anna
2011-10-01
Failures of fracture repair (nonunions) occur in 10% of all fractures. The use of mesenchymal stem cells (MSC) in tissue regeneration appears to be rationale, safe, and feasible. The contributions of MSC to the reparative process can occur through autocrine and paracrine effects. The primary objective of this study is to find a novel mean, by transplanting primary cultures of bone marrow-derived MSCs expressing insulin-like growth factor-I (MSC(IGF)), to promote these seed-and-soil actions of MSC to fully implement their regenerative abilities in fracture repair and nonunions. MSC(IGF) or traceable MSC(IGF)-Lac-Z were transplanted into wild-type or insulin-receptor-substrate knockout (Irs1(-/-)) mice with a stabilized tibia fracture. Healing was assessed using biomechanical testing, microcomputed tomography (μCT), and histological analyses. We found that systemically transplanted MSC(IGF) through autocrine and paracrine actions improved the fracture mechanical strength and increased new bone content while accelerating mineralization. We determined that IGF-I adapted the response of transplanted MSC(IGF) to promote their differentiation into osteoblasts. In vitro and in vivo studies showed that IGF-I-induced osteoglastogenesis in MSCs was dependent of an intact IRS1-PI3K signaling. Furthermore, using Irs1(-/-) mice as a nonunion fracture model through altered IGF signaling, we demonstrated that the autocrine effect of IGF-I on MSC restored the fracture new bone formation and promoted the occurrence of a well-organized callus that bridged the gap. A callus that was basically absent in Irs1(-/-) left untransplanted or transplanted with MSCs. We provided evidence of effects and mechanisms for transplanted MSC(IGF) in fracture repair and potentially to treat nonunions. Copyright © 2011 AlphaMed Press.
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Wang, Li; Gu, Zhenyang; Zhao, Xiaoli; Yang, Nan; Wang, Feiyan; Deng, Ailing; Zhao, Shasha; Luo, Lan; Wei, Huaping; Guan, Lixun; Gao, Zhe; Li, Yonghui; Wang, Lili; Liu, Daihong; Gao, Chunji
2016-12-15
Mesenchymal stromal cells (MSCs) are attractive agents for the prophylaxis of acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, safety concerns remain about their clinical application. In this study, we explored whether extracellular vesicles released from human umbilical cord-derived MSCs (hUC-MSC-EVs) could prevent aGVHD in a mouse model of allo-HSCT. hUC-MSC-EVs were intravenously administered to recipient mice on days 0 and 7 after allo-HSCT, and the prophylactic effects of hUC-MSC-EVs were assessed by observing the in vivo manifestations of aGVHD, histologic changes in target organs, and recipient mouse survival. We evaluated the effects of hUC-MSC-EVs on immune cells and inflammatory cytokines by flow cytometry and ProcartaPlex™ Multiplex Immunoassays, respectively. The in vitro effects of hUC-MSC-EVs were determined by mitogen-induced proliferation assays. hUC-MSC-EVs alleviated the in vivo manifestations of aGVHD and the associated histologic changes and significantly reduced the mortality of the recipient mice. Recipients treated with hUC-MSC-EVs had significantly lower frequencies and absolute numbers of CD3 + CD8 + T cells; reduced serum levels of IL-2, TNF-α, and IFN-γ; a higher ratio of CD3 + CD4 + and CD3 + CD8 + T cells; and higher serum levels of IL-10. An in vitro experiment demonstrated that hUC-MSC-EVs inhibited the mitogen-induced proliferation of splenocytes in a dose-dependent manner, and the cytokine changes were similar to those observed in vivo. This study indicated that hUC-MSC-EVs can prevent life-threatening aGVHD by modulating immune responses. These data provide the first evidence that hUC-MSC-EVs represent an ideal alternative in the prophylaxis of aGVHD after allo-HSCT.
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Wang, L; Li, P; Tian, Y; Li, Z; Lian, C; Ou, Q; Jin, C; Gao, F; Xu, J-Y; Wang, J; Wang, F; Zhang, J; Zhang, J; Li, W; Tian, H; Lu, L; Xu, G-T
2017-01-01
Human umbilical cord mesenchymal stem cells (hUC-MSCs) are potential candidates for treating retinal degeneration (RD). To further study the biology and therapeutic effects of the hUC-MSCs on retinal degeneration. Two hUC-MSC subpopulations, termed hUC-MSC1 and hUC-MSC2, were isolated by single-cell cloning method and their therapeutic functions were compared in RCS rat, a RD model. Although both subsets satisfied the basic requirements for hUC-MSCs, they were significantly different in morphology, proliferation rate, differentiation capacity, phenotype and gene expression. Furthermore, only the smaller, fibroblast-like, faster growing subset hUC-MSC1 displayed stronger colony forming potential as well as adipogenic and osteogenic differentiation capacities. When the two subsets were respectively transplanted into the subretinal spaces of RCS rats, both subsets survived, but only hUC-MSC1 expressed RPE cell markers Bestrophin and RPE65. More importantly, hUC-MSC1 showed stronger rescue effect on the retinal function as indicated by the higher b-wave amplitude on ERG examination, thicker retinal nuclear layer, and decreased apoptotic photoreceptors. When both subsets were treated with interleukin-6, mimicking the inflammatory environment when the cells were transplanted into the eyes with degenerated retina, hUC-MSC1 expressed much higher levels of trophic factors in comparison with hUC-MSC2. The data here, in addition to prove the heterogeneity of hUC-MSCs, confirmed that the stronger therapeutic effects of hUC-MSC1 were attributed to its stronger anti-apoptotic effect, paracrine of trophic factors and potential RPE cell differentiation capacity. Thus, the subset hUC-MSC1, not the other subset or the ungrouped hUC-MSCs should be used for effective treatment of RD. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.
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Mesenchymal Stromal Cells Modulate Monocytes Trafficking in Coxsackievirus B3‐Induced Myocarditis
Miteva, Kapka; Pappritz, Kathleen; El‐Shafeey, Muhammad; Dong, Fengquan; Ringe, Jochen; Tschöpe, Carsten
2017-01-01
Abstract Mesenchymal stromal cell (MSC) application in Coxsackievirus B3 (CVB3)‐induced myocarditis reduces myocardial inflammation and fibrosis, exerts prominent extra‐cardiac immunomodulation, and improves heart function. Although the abovementioned findings demonstrate the benefit of MSC application, the mechanism of the MSC immunomodulatory effects leading to a final cardioprotective outcome in viral myocarditis remains poorly understood. Monocytes are known to be a trigger of myocardial tissue inflammation. The present study aims at investigating the direct effect of MSC on the mobilization and trafficking of monocytes to the heart in CVB3‐induced myocarditis. One day post CVB3 infection, C57BL/6 mice were intravenously injected with 1 x 106 MSC and sacrificed 6 days later for molecular biology and flow cytometry analysis. MSC application reduced the severity of myocarditis, and heart and blood pro‐inflammatory Ly6Chigh and Ly6Cmiddle monocytes, while those were retained in the spleen. Anti‐inflammatory Ly6Clow monocytes increased in the blood, heart, and spleen of MSC‐treated CVB3 mice. CVB3 infection induced splenic myelopoiesis, while MSC application slightly diminished the spleen myelopoietic activity in CVB3 mice. Left ventricular (LV) mRNA expression of the chemokines monocyte chemotactic protein‐1 (MCP)−1, MCP‐3, CCL5, the adhesion molecules intercellular adhesion molecule‐1, vascular cell adhesion molecule‐1, the pro‐inflammatory cytokines interleukin‐6, interleukin‐12, tumor necrosis factor‐α, the pro‐fibrotic transforming growth factorβ1, and circulating MCP‐1 and MCP‐3 levels decreased in CVB3 MSC mice, while LV stromal cell‐derived factor‐1α RNA expression and systemic levels of fractalkine were increased in CVB3 MSC mice. MSC application in CVB3‐induced myocarditis modulates monocytes trafficking to the heart and could be a promising strategy for the resolution of cardiac inflammation and prevention of the disease progression. Stem Cells Translational Medicine 2017;6:1249–1261 PMID:28186704
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Anomalous Rayleigh scattering with dilute concentrations of elements of biological importance
NASA Astrophysics Data System (ADS)
Hugtenburg, Richard P.; Bradley, David A.
2004-01-01
The anomalous scattering factor (ASF) correction to the relativistic form-factor approximation for Rayleigh scattering is examined in support of its utilization in radiographic imaging. ASF corrected total cross-section data have been generated for a low resolution grid for the Monte Carlo code EGS4 for the biologically important elements, K, Ca, Mn, Fe, Cu and Zn. Points in the fixed energy grid used by EGS4 as well as 8 other points in the vicinity of the K-edge have been chosen to achieve an uncertainty in the ASF component of 20% according to the Thomas-Reiche-Kuhn sum rule and an energy resolution of 20 eV. Such data is useful for analysis of imaging with a quasi-monoenergetic source. Corrections to the sampled distribution of outgoing photons, due to ASF, are given and new total cross-section data including that of the photoelectric effect have been computed using the Slater exchange self-consistent potential with the Latter tail. A measurement of Rayleigh scattering in a dilute aqueous solution of manganese (II) was performed, this system enabling determination of the absolute cross-section, although background subtraction was necessary to remove K β fluorescence and resonant Raman scattering occurring within several 100 eV of the edge. Measurements confirm the presence of below edge bound-bound structure and variation in the structure due to the ionic state that are not currently included in tabulations.
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Chiral symmetry constraints on resonant amplitudes
NASA Astrophysics Data System (ADS)
Bruns, Peter C.; Mai, Maxim
2018-03-01
We discuss the impact of chiral symmetry constraints on the quark-mass dependence of meson resonance pole positions, which are encoded in non-perturbative parametrizations of meson scattering amplitudes. Model-independent conditions on such parametrizations are derived, which are shown to guarantee the correct functional form of the leading quark-mass corrections to the resonance pole positions. Some model amplitudes for ππ scattering, widely used for the determination of ρ and σ resonance properties from results of lattice simulations, are tested explicitly with respect to these conditions.
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Kouri, Donald J [Houston, TX; Vijay, Amrendra [Houston, TX; Zhang, Haiyan [Houston, TX; Zhang, Jingfeng [Houston, TX; Hoffman, David K [Ames, IA
2007-05-01
A method and system for solving the inverse acoustic scattering problem using an iterative approach with consideration of half-off-shell transition matrix elements (near-field) information, where the Volterra inverse series correctly predicts the first two moments of the interaction, while the Fredholm inverse series is correct only for the first moment and that the Volterra approach provides a method for exactly obtaining interactions which can be written as a sum of delta functions.
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Holographic corrections to meson scattering amplitudes
NASA Astrophysics Data System (ADS)
Armoni, Adi; Ireson, Edwin
2017-06-01
We compute meson scattering amplitudes using the holographic duality between confining gauge theories and string theory, in order to consider holographic corrections to the Veneziano amplitude and associated higher-point functions. The generic nature of such computations is explained, thanks to the well-understood nature of confining string backgrounds, and two different examples of the calculation in given backgrounds are used to illustrate the details. The effect we discover, whilst only qualitative, is re-obtainable in many such examples, in four-point but also higher point amplitudes.
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Lohan, Paul; Treacy, Oliver; Griffin, Matthew D.; Ritter, Thomas; Ryan, Aideen E.
2017-01-01
Mesenchymal stromal cells (MSC) have been used to treat a broad range of disease indications such as acute and chronic inflammatory disorders, autoimmune diseases, and transplant rejection due to their potent immunosuppressive/anti-inflammatory properties. The breadth of their usage is due in no small part to the vast quantity of published studies showing their ability to modulate multiple immune cell types of both the innate and adaptive immune response. While patient-derived (autologous) MSC may be the safer choice in terms of avoiding unwanted immune responses, factors including donor comorbidities may preclude these cells from use. In these situations, allogeneic MSC derived from genetically unrelated individuals must be used. While allogeneic MSC were initially believed to be immune-privileged, substantial evidence now exists to prove otherwise with multiple studies documenting specific cellular and humoral immune responses against donor antigens following administration of these cells. In this article, we will review recent published studies using non-manipulated, inflammatory molecule-activated (licensed) and differentiated allogeneic MSC, as well as MSC extracellular vesicles focusing on the immune responses to these cells and whether or not such responses have an impact on allogeneic MSC-mediated safety and efficacy. PMID:29225601
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Monsel, Antoine; Zhu, Ying-gang; Gudapati, Varun; Lim, Hyungsun; Lee, Jae W.
2017-01-01
Introduction Acute respiratory distress syndrome is a major cause of respiratory failure in critically ill patients. Despite extensive research into its pathophysiology, mortality remains high. No effective pharmacotherapy exists. Based largely on numerous preclinical studies, administration of mesenchymal stem or stromal cell (MSC) as a therapeutic for acute lung injury holds great promise, and clinical trials are currently underway. However, concern for the use of stem cells, specifically the risk of iatrogenic tumor formation, remains unresolved. Accumulating evidence now suggest that novel cell-free therapies including MSC-derived conditioned medium and extracellular vesicles released from MSCs might constitute compelling alternatives. Areas covered The current review summarizes the preclinical studies testing MSC conditioned medium and/or MSC extracellular vesicles as treatment for acute lung injury and other inflammatory lung diseases. Expert opinion While certain logistical obstacles limit the clinical applications of MSC conditioned medium such as the volume required for treatment, the therapeutic application of MSC extracellular vesicles remains promising, primarily due to ability of extracellular vesicles to maintain the functional phenotype of the parent cell. However, utilization of MSC extracellular vesicles will require large-scale production and standardization concerning identification, characterization and quantification. PMID:27011289
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Three Dimensional Architecture of Membrane-Embedded MscS in the Closed Conformation
Vásquez, Valeria; Sotomayor, Marcos; Cortes, D. Marien; Roux, Benoît; Schulten, Klaus; Perozo, Eduardo
2009-01-01
The mechanosensitive channel of small conductance (MscS) is part of a coordinated response to osmotic challenges in E. coli. MscS opens as a result of membrane tension changes, thereby releasing small solutes and effectively acting as an osmotic safety valve. Both, the functional state depicted by its crystal structure and its gating mechanism remain unclear. Here, we combine site-directed spin labeling, electron paramagnetic resonance (EPR) spectroscopy, and molecular dynamics simulations with novel energy restraints based on experimental EPR data to investigate the native transmembrane and periplasmic molecular architecture of closed MscS in a lipid bilayer. In the closed conformation, MscS shows a more compact transmembrane domain than in the crystal structure, characterized by a realignment of the transmembrane segments towards the normal of the membrane. The previously unresolved NH2-terminus forms a short helical hairpin capping the extracellular ends of TM1 and TM2 and in close interaction with the bilayer interface. The present three-dimensional model of membrane-embedded MscS in the closed state represents a key step in determining the molecular mechanism of MscS gating. PMID:18343404
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Mesenchymal Stem Cells Respond to Hypoxia by Increasing Diacylglycerols.
Lakatos, Kinga; Kalomoiris, Stefanos; Merkely, Béla; Nolta, Jan A; Fierro, Fernando A
2016-02-01
Mesenchymal stem cells (MSC) are currently being tested clinically for a plethora of conditions, with most approaches relying on the secretion of paracrine signals by MSC to modulate the immune system, promote wound healing, and induce angiogenesis. Hypoxia has been shown to affect MSC proliferation, differentiation, survival and secretory profile. Here, we investigate changes in the lipid composition of human bone marrow-derived MSC after exposure to hypoxia. Using mass spectrometry, we compared the lipid profiles of MSC derived from five different donors, cultured for two days in either normoxia (control) or hypoxia (1% oxygen). Hypoxia induced a significant increase of total triglycerides, fatty acids and diacylglycerols (DG). Remarkably, reduction of DG levels using the phosphatidylcholine-specific phospholipase C inhibitor D609 inhibited the secretion of VEGF and Angiopoietin-2, but increased the secretion of interleukin-8, without affecting significantly their respective mRNA levels. Functionally, incubation of MSC in hypoxia with D609 inhibited the potential of the cells to promote migration of human endothelial cells in a wound/scratch assay. Hence, we show that hypoxia induces in MSC an increase of DG that may affect the angiogenic potential of these cells. © 2015 Wiley Periodicals, Inc.
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Interactions of Human Endothelial and Multipotent Mesenchymal Stem Cells in Cocultures
Ern, Christina; Krump-Konvalinkova, Vera; Docheva, Denitsa; Schindler, Stefanie; Rossmann, Oliver; Böcker, Wolfgang; Mutschler, Wolf; Schieker, Matthias
2010-01-01
Current strategies for tissue engineering of bone rely on the implantation of scaffolds, colonized with human mesenchymal stem cells (hMSC), into a recipient. A major limitation is the lack of blood vessels. One approach to enhance the scaffold vascularisation is to supply the scaffolds with endothelial cells (EC). The main goal of this study was to establish a coculture system of hMSC and EC for the purposes of bone tissue engineering. Therefore, the cell behaviour, proliferation and differentiation capacity in various cell culture media as well as cell interactions in the cocultures were evaluated. The differentiation capacity of hMSC along osteogenic, chondrogenic, and adipogenic lineage was impaired in EC medium while in a mixed EC and hMSC media, hMSC maintained osteogenic differentiation. In order to identify and trace EC in the cocultures, EC were transduced with eGFP. Using time-lapse imaging, we observed that hMSC and EC actively migrated towards cells of their own type and formed separate clusters in long term cocultures. The scarcity of hMSC and EC contacts in the cocultures suggest the influence of growth factor-mediated cell interactions and points to the necessity of further optimization of the coculture conditions. PMID:21625373
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NASA Astrophysics Data System (ADS)
Dumouchel, Tyler; Thorn, Stephanie; Kordos, Myra; DaSilva, Jean; Beanlands, Rob S. B.; deKemp, Robert A.
2012-07-01
Quantification in cardiac mouse positron emission tomography (PET) imaging is limited by the imaging spatial resolution. Spillover of left ventricle (LV) myocardial activity into adjacent organs results in partial volume (PV) losses leading to underestimation of myocardial activity. A PV correction method was developed to restore accuracy of the activity distribution for FDG mouse imaging. The PV correction model was based on convolving an LV image estimate with a 3D point spread function. The LV model was described regionally by a five-parameter profile including myocardial, background and blood activities which were separated into three compartments by the endocardial radius and myocardium wall thickness. The PV correction was tested with digital simulations and a physical 3D mouse LV phantom. In vivo cardiac FDG mouse PET imaging was also performed. Following imaging, the mice were sacrificed and the tracer biodistribution in the LV and liver tissue was measured using a gamma-counter. The PV correction algorithm improved recovery from 50% to within 5% of the truth for the simulated and measured phantom data and image uniformity by 5-13%. The PV correction algorithm improved the mean myocardial LV recovery from 0.56 (0.54) to 1.13 (1.10) without (with) scatter and attenuation corrections. The mean image uniformity was improved from 26% (26%) to 17% (16%) without (with) scatter and attenuation corrections applied. Scatter and attenuation corrections were not observed to significantly impact PV-corrected myocardial recovery or image uniformity. Image-based PV correction algorithm can increase the accuracy of PET image activity and improve the uniformity of the activity distribution in normal mice. The algorithm may be applied using different tracers, in transgenic models that affect myocardial uptake, or in different species provided there is sufficient image quality and similar contrast between the myocardium and surrounding structures.
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Fast analytical scatter estimation using graphics processing units.
Ingleby, Harry; Lippuner, Jonas; Rickey, Daniel W; Li, Yue; Elbakri, Idris
2015-01-01
To develop a fast patient-specific analytical estimator of first-order Compton and Rayleigh scatter in cone-beam computed tomography, implemented using graphics processing units. The authors developed an analytical estimator for first-order Compton and Rayleigh scatter in a cone-beam computed tomography geometry. The estimator was coded using NVIDIA's CUDA environment for execution on an NVIDIA graphics processing unit. Performance of the analytical estimator was validated by comparison with high-count Monte Carlo simulations for two different numerical phantoms. Monoenergetic analytical simulations were compared with monoenergetic and polyenergetic Monte Carlo simulations. Analytical and Monte Carlo scatter estimates were compared both qualitatively, from visual inspection of images and profiles, and quantitatively, using a scaled root-mean-square difference metric. Reconstruction of simulated cone-beam projection data of an anthropomorphic breast phantom illustrated the potential of this method as a component of a scatter correction algorithm. The monoenergetic analytical and Monte Carlo scatter estimates showed very good agreement. The monoenergetic analytical estimates showed good agreement for Compton single scatter and reasonable agreement for Rayleigh single scatter when compared with polyenergetic Monte Carlo estimates. For a voxelized phantom with dimensions 128 × 128 × 128 voxels and a detector with 256 × 256 pixels, the analytical estimator required 669 seconds for a single projection, using a single NVIDIA 9800 GX2 video card. Accounting for first order scatter in cone-beam image reconstruction improves the contrast to noise ratio of the reconstructed images. The analytical scatter estimator, implemented using graphics processing units, provides rapid and accurate estimates of single scatter and with further acceleration and a method to account for multiple scatter may be useful for practical scatter correction schemes.
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Liu, Zheng; Yang, Yang; Bai, Ying; Huang, Yu; Nan, Zhongren; Zhao, Chuanyan; Ma, Jianmin; Wang, Houcheng
2016-10-01
The effect of sewage sludge on the mobility and the bioavailability of trace metals in plant-soil systems have aroused wide interested and been widely explored. Based on a wheat-cultivating experiment, the effect of municipal sludge compost (MSC) on the mobility and bioavailability of Cd in a soil-wheat system was studied. With the application of MSC, soil organic matter (SOM), total nitrogen (TN), and total phosphorus (TP) in the soil increased significantly, while concentrations of trace metals (Cu, Zn, Ni, Pb, Cd) were below the China's minimum thresholds. The application of MSC could improve wheat growth. The application of MSC at the rate of 0.5 % had no significant effect on the chemical fraction distribution of Cd in soil. In two soil treatments, Cd mainly existed in the labile chemical fractions (exchangeable chemical fraction (EXCF) and carbonate chemical fraction (CABF)). However, the application of MSC could reduce accumulation of Cd by wheat. Cd contents in each part of the MSC-applied wheat were significantly less than that of non-MSC-applied wheat. In the tested soils, the extractable concentrations decreased in the order: EDTA > MgCl 2 ≈ NH 4 OAc > DTPA. There were no significant differences between soil treatments in the amounts of extractable Cd when the extraction was done under neutral conditions, although significant differences were observed when the extraction was done under alkaline conditions. In this study, the DTPA extraction procedure provided a good indication of Cd bioavailability. Our results suggest that, in the short term at least, amending soils with MSC may benefit crop dry matter production while not increasing the risk of human exposure to Cd through consumption of wheat grown on MSC-amended soils.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Sassoli, Chiara; Nosi, Daniele; Tani, Alessia
Recent studies indicate that mesenchymal stromal cell (MSC) transplantation improves healing of injured and diseased skeletal muscle, although the mechanisms of benefit are poorly understood. In the present study, we investigated whether MSCs and/or their trophic factors were able to regulate matrix metalloproteinase (MMP) expression and activity in different cells of the muscle tissue. MSCs in co-culture with C2C12 cells or their conditioned medium (MSC-CM) up-regulated MMP-2 and MMP-9 expression and function in the myoblastic cells; these effects were concomitant with the down-regulation of the tissue inhibitor of metalloproteinases (TIMP)-1 and -2 and with increased cell motility. In the singlemore » muscle fiber experiments, MSC-CM administration increased MMP-2/9 expression in Pax-7{sup +} satellite cells and stimulated their mobilization, differentiation and fusion. The anti-fibrotic properties of MSC-CM involved also the regulation of MMPs by skeletal fibroblasts and the inhibition of their differentiation into myofibroblasts. The treatment with SB-3CT, a potent MMP inhibitor, prevented in these cells, the decrease of α-smooth actin and type-I collagen expression induced by MSC-CM, suggesting that MSC-CM could attenuate the fibrogenic response through mechanisms mediated by MMPs. Our results indicate that growth factors and cytokines released by these cells may modulate the fibrotic response and improve the endogenous mechanisms of muscle repair/regeneration. - Highlights: • MSC-CM contains paracrine factors that up-regulate MMP expression and function in different skeletal muscle cells. • MSC-CM promotes myoblast and satellite cell migration, proliferation and differentiation. • MSC-CM negatively interferes with fibroblast-myoblast transition in primary skeletal fibroblasts. • Paracrine factors from MSCs modulate the fibrotic response and improve the endogenous mechanisms of muscle regeneration.« less
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Le Blon, Debbie; Hoornaert, Chloé; Daans, Jasmijn; Santermans, Eva; Hens, Niel; Goossens, Herman; Berneman, Zwi; Ponsaerts, Peter
2014-09-01
Although implantation of cellular material in the central nervous system (CNS) is a key direction in CNS regenerative medicine, this approach is currently limited by the occurrence of strong endogenous immune cell responses. In a model of mesenchymal stem cell (MSC) grafting in the CNS of immune-competent mice, we previously described that MSC grafts become highly surrounded and invaded by Iba1(+) myeloid cells (microglia and/or macrophages). Here, following grafting of blue fluorescent protein (BFP)-expressing MSC in the CNS of CX3CR1(+/-) and CX3CR1(-/-) mice, our results indicate: (1) that the observed inflammatory response is independent of the fractalkine signalling axis, and (2) that a significant spatial distribution of Iba1(+) inflammatory cells occurs, in which Iba1(+) CX3CR1(+) myeloid cells mainly surround the MSC graft and Iba1(+) CX3CR1(-) myeloid cells mainly invade the graft at 10 days post transplantation. Although Iba1(+) CX3CR1(+) myeloid cells are considered to be of resident microglial origin, Iba1(+) CX3CR1(-) myeloid cells are most likely of peripheral monocyte/macrophage origin. In order to confirm the latter, we performed MSC-BFP grafting experiments in the CNS of eGFP(+) bone marrow chimeric C57BL/6 mice. Analysis of MSC-BFP grafts in the CNS of these mice confirmed our observation that peripheral monocytes/macrophages invade the MSC graft and that resident microglia surround the MSC graft site. Furthermore, analysis of major histocompatibility complex class II (MHCII) expression revealed that mainly macrophages, but not microglia, express this M1 pro-inflammatory marker in the context of MSC grafting in the CNS. These results again highlight the complexity of cell implantation immunology in the CNS.
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Russell, K A; Koch, T G
2016-03-01
Multipotent mesenchymal stromal cells (MSC) are often culture-expanded in vitro. Presently, expansion medium (EM) for MSC is supplemented with fetal bovine serum (FBS). However, increasing cost, variable composition and potential risks associated with bovine antigens call for alternatives. Platelet lysate (PL) has shown promise as an alternative supplement. To determine how equine umbilical cord blood (CB) MSC proliferate in EM enriched with PL or FBS at various concentrations. Randomised dose escalation study. Platelet concentrate was generated from 5 equine whole blood samples through a double centrifugation method and standardised to 1 × 10(12) platelets/l prior to a freeze/thaw cycle to produce PL. Pooled PL or pooled FBS was added to EM at concentrations of 5% to 60%. Proliferation of 4 equine CB-MSC cultures was determined after 4 days using a resazurin semiquantitative assay. Cord blood-MSC proliferated with a dose-dependent response with no significant difference found between PL and FBS up to a 30% concentration. Beyond 30%, proliferation fell in the PL-cultured cells, while continued dose-dependent proliferation was noted in the FBS-cultured cells. Despite reduced cell numbers in high PL concentrations, live/dead staining revealed that adherent cells remained viable. Expansion medium enriched with PL can support short-term equine CB-MSC proliferation at conventional culture concentrations. Based on the unexpected suppression of CB-MSC at higher PL concentrations, an in vivo dose study is indicated to investigate if combinational therapies of CB-MSC and platelet-rich plasma are associated with synergistic or antagonistic effect on CB-MSC function. © 2015 EVJ Ltd.
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Foglietta, Federica; Duchi, Serena; Canaparo, Roberto; Varchi, Greta; Lucarelli, Enrico; Dozza, Barbara; Serpe, Loredana
2017-03-15
Mesenchymal stem cells (MSC) possess the distinctive feature of homing in on and engrafting into the tumor stroma making their therapeutic applications in cancer treatment very promising. Research into new effectors and external stimuli, which can selectively trigger the release of cytotoxic species from MSC toward the cancer cells, significantly raises their potential. Shock waves (SW) have recently gained recognition for their ability to induce specific biological effects, such as the local generation of cytotoxic reactive oxygen species (ROS) in a non-invasive and tunable manner. We thus investigate whether MSC are able to generate ROS and, in turn, affect cancer cell growth when in co-culture with human glioblastoma (U87) or osteosarcoma (U2OS) cells and exposed to SW. MSC were found to be the cell line that was most sensitive to SW treatment as shown by SW-induced ROS production and cytotoxicity. Notably, U87 and U2OS cancer cell growth was unaffected by SW exposure. However, significant decreases in cancer cell growth, 1.8 fold for U87 and 2.3 fold for U2OS, were observed 24h after the SW treatment of MSC co-cultures with cancer cells. The ROS production induced in MSC by SW exposure was then responsible for lipid peroxidation and cell death in U87 and U2OS cells co-cultured with MSC. This experiment highlights the unique ability of MSC to generate ROS upon SW treatment and induce the cell death of co-cultured cancer cells. SW might therefore be proposed as an innovative tool for MSC-mediated cancer treatment. Copyright © 2017 Elsevier Inc. All rights reserved.
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Gómez-Mauricio, Guadalupe; Moscoso, Isabel; Martín-Cancho, María-Fernanda; Crisóstomo, Verónica; Prat-Vidal, Cristina; Báez-Díaz, Claudia; Sánchez-Margallo, Francisco M; Bernad, Antonio
2016-07-16
Insulin-like growth factor 1 (IGF-1) and hepatocyte growth factor (HGF) are among the most promising growth factors for promoting cardiorepair. Here, we evaluated the combination of cell- and gene-based therapy using mesenchymal stem cells (MSC) genetically modified to overexpress IGF-1 or HGF to treat acute myocardial infarction (AMI) in a porcine model. Pig MSC from adipose tissue (paMSC) were genetically modified for evaluation of different therapeutic strategies to improve AMI treatment. Three groups of infarcted Large White pigs were compared (I, control, non-transplanted; II, transplanted with paMSC-GFP (green fluorescent protein); III, transplanted with paMSC-IGF-1/HGF). Cardiac function was evaluated non-invasively using magnetic resonance imaging (MRI) for 1 month. After euthanasia and sampling of the animal, infarcted areas were studied by histology and immunohistochemistry. Intramyocardial transplant in a porcine infarct model demonstrated the safety of paMSC in short-term treatments. Treatment with paMSC-IGF-1/HGF (1:1) compared with the other groups showed a clear reduction in inflammation in some sections analyzed and promoted angiogenic processes in ischemic tissue. Although cardiac function parameters were not significantly improved, cell retention and IGF-1 overexpression was confirmed within the myocardium. The simultaneous administration of IGF-1- and HGF-overexpressing paMSC appears not to promote a synergistic effect or effective repair. The combined enhancement of neovascularization and fibrosis in paMSC-IGF-1/HGF-treated animals nonetheless suggests that sustained exposure to high IGF-1 + HGF levels promotes beneficial as well as deleterious effects that do not improve overall cardiac regeneration.
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Tobin, L M; Healy, M E; English, K; Mahon, B P
2013-05-01
Acute graft-versus-host disease (aGVHD) is a life-threatening complication following allogeneic haematopoietic stem cell transplantation (HSCT), occurring in up to 30-50% of patients who receive human leucocyte antigen (HLA)-matched sibling transplants. Current therapies for steroid refractory aGVHD are limited, with the prognosis of patients suboptimal. Mesenchymal stem or stromal cells (MSC), a heterogeneous cell population present in many tissues, display potent immunomodulatory abilities. Autologous and allogeneic ex-vivo expanded human MSC have been utilized to treat aGVHD with promising results, but the mechanisms of therapeutic action remain unclear. Here a robust humanized mouse model of aGVHD based on delivery of human peripheral blood mononuclear cells (PBMC) to non-obese diabetic (NOD)-severe combined immunodeficient (SCID) interleukin (IL)-2rγ(null) (NSG) mice was developed that allowed the exploration of the role of MSC in cell therapy. MSC therapy resulted in the reduction of liver and gut pathology and significantly increased survival. Protection was dependent upon the timing of MSC therapy, with conventional MSC proving effective only after delayed administration. In contrast, interferon (IFN)-γ-stimulated MSC were effective when delivered with PBMC. The beneficial effect of MSC therapy in this model was not due to the inhibition of donor PBMC chimerism, as CD45(+) and T cells engrafted successfully in this model. MSC therapy did not induce donor T cell anergy, FoxP3(+) T regulatory cells or cause PBMC apoptosis in this model; however, it was associated with the direct inhibition of donor CD4(+) T cell proliferation and reduction of human tumour necrosis factor-α in serum. © 2012 British Society for Immunology.
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Different wound healing properties of dermis, adipose, and gingiva mesenchymal stromal cells.
Boink, Mireille A; van den Broek, Lenie J; Roffel, Sanne; Nazmi, Kamran; Bolscher, Jan G M; Gefen, Amit; Veerman, Enno C I; Gibbs, Susan
2016-01-01
Oral wounds heal faster and with better scar quality than skin wounds. Deep skin wounds where adipose tissue is exposed, have a greater risk of forming hypertrophic scars. Differences in wound healing and final scar quality might be related to differences in mesenchymal stromal cells (MSC) and their ability to respond to intrinsic (autocrine) and extrinsic signals, such as human salivary histatin, epidermal growth factor, and transforming growth factor beta1. Dermis-, adipose-, and gingiva-derived MSC were compared for their regenerative potential with regards to proliferation, migration, and matrix contraction. Proliferation was assessed by cell counting and migration using a scratch wound assay. Matrix contraction and alpha smooth muscle actin was assessed in MSC populated collagen gels, and also in skin and gingival full thickness tissue engineered equivalents (reconstructed epithelium on MSC populated matrix). Compared to skin-derived MSC, gingiva MSC showed greater proliferation and migration capacity, and less matrix contraction in full thickness tissue equivalents, which may partly explain the superior oral wound healing. Epidermal keratinocytes were required for enhanced adipose MSC matrix contraction and alpha smooth muscle actin expression, and may therefore contribute to adverse scarring in deep cutaneous wounds. Histatin enhanced migration without influencing proliferation or matrix contraction in all three MSC, indicating that salivary peptides may have a beneficial effect on wound closure in general. Transforming growth factor beta1 enhanced contraction and alpha smooth muscle actin expression in all three MSC types when incorporated into collagen gels. Understanding the mechanisms responsible for the superior oral wound healing will aid us to develop advanced strategies for optimal skin regeneration, wound healing and scar formation. © 2015 by the Wound Healing Society.
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CD146/MCAM defines functionality of human bone marrow stromal stem cell populations.
Harkness, Linda; Zaher, Walid; Ditzel, Nicholas; Isa, Adiba; Kassem, Moustapha
2016-01-11
Identification of surface markers for prospective isolation of functionally homogenous populations of human skeletal (stromal, mesenchymal) stem cells (hMSCs) is highly relevant for cell therapy protocols. Thus, we examined the possible use of CD146 to subtype a heterogeneous hMSC population. Using flow cytometry and cell sorting, we isolated two distinct hMSC-CD146(+) and hMSC-CD146(-) cell populations from the telomerized human bone marrow-derived stromal cell line (hMSC-TERT). Cells were examined for differences in their size, shape and texture by using high-content analysis and additionally for their ability to differentiate toward osteogenesis in vitro and form bone in vivo, and their migrational ability in vivo and in vitro was investigated. In vitro, the two cell populations exhibited similar growth rate and differentiation capacity to osteoblasts and adipocytes on the basis of gene expression and protein production of lineage-specific markers. In vivo, hMSC-CD146(+) and hMSC-CD146(-) cells formed bone and bone marrow organ when implanted subcutaneously in immune-deficient mice. Bone was enriched in hMSC-CD146(-) cells (12.6 % versus 8.1 %) and bone marrow elements enriched in implants containing hMSC-CD146(+) cells (0.5 % versus 0.05 %). hMSC-CD146(+) cells exhibited greater chemotactic attraction in a transwell migration assay and, when injected intravenously into immune-deficient mice following closed femoral fracture, exhibited wider tissue distribution and significantly increased migration ability as demonstrated by bioluminescence imaging. Our studies demonstrate that CD146 defines a subpopulation of hMSCs capable of bone formation and in vivo trans-endothelial migration and thus represents a population of hMSCs suitable for use in clinical protocols of bone tissue regeneration.
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Boura, Joana S; Santos, Francisco Dos; Gimble, Jeffrey M; Cardoso, Carla M P; Madeira, Catarina; Cabral, Joaquim M S; Silva, Cláudia Lobato da
2013-02-01
Nonviral gene delivery to human mesenchymal stem/stromal cells (MSC) can be considered a very promising strategy to improve their intrinsic features, amplifying the therapeutic potential of these cells for clinical applications. In this work, we performed a comprehensive comparison of liposome-mediated gene transfer efficiencies to MSC derived from different human sources-bone marrow (BM MSC), adipose tissue-derived cells (ASC), and umbilical cord matrix (UCM MSC). The results obtained using a green fluorescent protein (GFP)-encoding plasmid indicated that MSC isolated from BM and UCM are more amenable to genetic modification when compared to ASC as they exhibited superior levels of viable, GFP(+) cells 48 hr post-transfection, 58 ± 7.1% and 54 ± 3.8%, respectively, versus 33 ± 4.7%. For all cell sources, high cell recoveries (≈50%) and viabilities (>85%) were achieved, and the transgene expression was maintained for 10 days. Levels of plasmid DNA uptake, as well as kinetics of transgene expression and cellular division, were also determined. Importantly, modified cells were found to retain their characteristic immunophenotypic profile and multilineage differentiation capacity. By using the lipofection protocol optimized herein, we were able to maximize transfection efficiencies to human MSC (maximum of 74% total GFP(+) cells) and show that lipofection is a promising transfection strategy for MSC genetic modification, especially when a transient expression of a therapeutic gene is required. Importantly, we also clearly demonstrated that intrinsic features of MSC from different sources should be taken into consideration when developing and optimizing strategies for MSC engineering with a therapeutic gene.
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Ramezanifard, Rouhallah; Kabiri, Mahboubeh; Hanaee Ahvaz, Hana
2017-01-01
Regarding the inadequate healing capability of cartilage tissue, cell-based therapy is making the future of cartilage repair and regeneration. Mesenchymal stem cells (MSC) have shown great promise in cartilage regeneration. However, a yet-unresolved issue is the emergence of hypertrophic and pathologic markers during in vitro MSC chondrogenesis. Articular chondrocytes (AC) can suppress the undesired hypertrophy when co-cultured with MSC. On the other hand, platelet rich plasma (PRP), is considered potentially effective for cartilage repair and in-vitro chondrogenesis. We thus aimed to harness chondro-promotive effects of PRP and hypertrophic-suppressive effects of AC:MSC co-culture to achieve a more functional cartilage neo-tissue. We used PRP or conventional-differentiation chondrogenic media (ConvDiff) in MSC mono-cultures and AC:MSC co-cultures. We assessed gene expression of chondrogenic and hypertrophic markers using real-time RT-PCR and immunostaining. Alkaline-phosphatase activity (ALP) and calcium content of the pellets were quantified. We also measured VEGF and TNF-α secretion via ELISA. We showed PRP had higher chondrogenic potential (in mRNA and protein level) and hypertrophic-suppressive effects than Conv-Diff (mRNA level). Co-culturing reduced ALP while PRP increased calcium deposition. In all four groups, TNF-α was down-regulated compared to MSC controls, with co-cultures receiving ConvDiff media secreting the least. Meanwhile, the only group with increased VEGF secretion was PRP-mono-cultures. We observed synergistic effects for PRP and AC:MSC co-culture in enhancing chondrogenesis. Inclusion of AC reduced hypertrophic markers and angiogenic potential in PRP groups. We thus propose that combination of PRP and co-culture would favor chondrogenesis while alleviate but not totally eradicate undesired hypertrophic and pathologic responses. PMID:28900383
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NASA Astrophysics Data System (ADS)
Dhakal, Sagar; Peng, Yankun; Li, Yongyu; Chao, Kuanglin; Qin, Jianwei; Zhang, Leilei; Xu, Tianfeng
2014-05-01
Different chemicals are sprayed in fruits and vegetables before and after harvest for better yield and longer shelf-life of crops. Cases of pesticide poisoning to human health are regularly reported due to excessive application of such chemicals for greater economic benefit. Different analytical technologies exist to detect trace amount of pesticides in fruits and vegetables, but are expensive, sample destructive, and require longer processing time. This study explores the application of Raman spectroscopy for rapid and non-destructive detection of pesticide residue in agricultural products. Raman spectroscopy with laser module of 785 nm was used to collect Raman spectral information from the surface of Gala apples contaminated with different concentrations of commercially available organophosphorous (48% chlorpyrifos) pesticide. Apples within 15 days of harvest from same orchard were used in this study. The Raman spectral signal was processed by Savitzky-Golay (SG) filter for noise removal, Multiplicative Scatter Correction (MSC) for drift removal and finally polynomial fitting was used to eliminate the fluorescence background. The Raman spectral peak at 677 cm-1 was recognized as Raman fingerprint of chlorpyrifos. Presence of Raman peak at 677 cm-1 after fluorescence background removal was used to develop classification model (presence and absence of pesticide). The peak intensity was correlated with actual pesticide concentration obtained using Gas Chromatography and MLR prediction model was developed with correlation coefficient of calibration and validation of 0.86 and 0.81 respectively. Result shows that Raman spectroscopy is a promising tool for rapid, real-time and non-destructive detection of pesticide residue in agro-products.
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[Measurement of Water COD Based on UV-Vis Spectroscopy Technology].
Wang, Xiao-ming; Zhang, Hai-liang; Luo, Wei; Liu, Xue-mei
2016-01-01
Ultraviolet/visible (UV/Vis) spectroscopy technology was used to measure water COD. A total of 135 water samples were collected from Zhejiang province. Raw spectra with 3 different pretreatment methods (Multiplicative Scatter Correction (MSC), Standard Normal Variate (SNV) and 1st Derivatives were compared to determine the optimal pretreatment method for analysis. Spectral variable selection is an important strategy in spectrum modeling analysis, because it tends to parsimonious data representation and can lead to multivariate models with better performance. In order to simply calibration models, the preprocessed spectra were then used to select sensitive wavelengths by competitive adaptive reweighted sampling (CARS), Random frog and Successive Genetic Algorithm (GA) methods. Different numbers of sensitive wavelengths were selected by different variable selection methods with SNV preprocessing method. Partial least squares (PLS) was used to build models with the full spectra, and Extreme Learning Machine (ELM) was applied to build models with the selected wavelength variables. The overall results showed that ELM model performed better than PLS model, and the ELM model with the selected wavelengths based on CARS obtained the best results with the determination coefficient (R2), RMSEP and RPD were 0.82, 14.48 and 2.34 for prediction set. The results indicated that it was feasible to use UV/Vis with characteristic wavelengths which were obtained by CARS variable selection method, combined with ELM calibration could apply for the rapid and accurate determination of COD in aquaculture water. Moreover, this study laid the foundation for further implementation of online analysis of aquaculture water and rapid determination of other water quality parameters.
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Mesenchymal Stem Cells – Sources and Clinical Applications
Klingemann, Hans; Matzilevich, David; Marchand, James
2008-01-01
Summary Although mesenchymal stem cells (MSC) from different tissue sources share many characteristics and generally fulfill accepted criteria for MSC (plastic adherence, certain surface marker expression, and ability to differentiate into mesenchymal tissues), we are increasingly learning that they can be distinguished at the level of cytokine production and gene expression profiles. Their ability to differentiate into different tissues including endodermal and ectodermal lineages, also varies according to tissue origin. Importantly, MSC from fetal sources can undergo more cell divisions before they reach senescence than MSC from adult tissue such as bone marrow or adipose tissue. As we learn more about the differentiation and plasticity of MSC from different sources, health care providers in the future will use them tailored to different medical indications. PMID:21512642
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Mahoney, Peter; Carr, Debra; Arm, Richard; Gibb, Iain; Hunt, Nicholas; Delaney, Russ J
2018-03-01
The aim of this work was to further develop a synthetic model of ballistic head injury by the addition of skin and soft tissue layers to an anatomically correct polyurethane skull filled with gelatine 10% by mass. Six head models were impacted with 7.62 x 39 mm full metal jacket mild steel core (FMJ MSC) bullets with a mean velocity of 652 m/s. The impact events were filmed with high-speed cameras. The models were imaged pre- and post-impact using computed tomography. The models were assessed post impact by two experienced Home Office pathologists and the images assessed by an experienced military radiologist. The findings were scored against real injuries. The entry wounds, exit wounds and fracture patterns were scored positively, but the synthetic skin and soft tissue layer was felt to be too extendable. Further work is ongoing to address this.
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Xu, Yuan; Bai, Ti; Yan, Hao; Ouyang, Luo; Pompos, Arnold; Wang, Jing; Zhou, Linghong; Jiang, Steve B.; Jia, Xun
2015-01-01
Cone-beam CT (CBCT) has become the standard image guidance tool for patient setup in image-guided radiation therapy. However, due to its large illumination field, scattered photons severely degrade its image quality. While kernel-based scatter correction methods have been used routinely in the clinic, it is still desirable to develop Monte Carlo (MC) simulation-based methods due to their accuracy. However, the high computational burden of the MC method has prevented routine clinical application. This paper reports our recent development of a practical method of MC-based scatter estimation and removal for CBCT. In contrast with conventional MC approaches that estimate scatter signals using a scatter-contaminated CBCT image, our method used a planning CT image for MC simulation, which has the advantages of accurate image intensity and absence of image truncation. In our method, the planning CT was first rigidly registered with the CBCT. Scatter signals were then estimated via MC simulation. After scatter signals were removed from the raw CBCT projections, a corrected CBCT image was reconstructed. The entire workflow was implemented on a GPU platform for high computational efficiency. Strategies such as projection denoising, CT image downsampling, and interpolation along the angular direction were employed to further enhance the calculation speed. We studied the impact of key parameters in the workflow on the resulting accuracy and efficiency, based on which the optimal parameter values were determined. Our method was evaluated in numerical simulation, phantom, and real patient cases. In the simulation cases, our method reduced mean HU errors from 44 HU to 3 HU and from 78 HU to 9 HU in the full-fan and the half-fan cases, respectively. In both the phantom and the patient cases, image artifacts caused by scatter, such as ring artifacts around the bowtie area, were reduced. With all the techniques employed, we achieved computation time of less than 30 sec including the time for both the scatter estimation and CBCT reconstruction steps. The efficacy of our method and its high computational efficiency make our method attractive for clinical use. PMID:25860299
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NASA Astrophysics Data System (ADS)
Bezur, L.; Marshall, J.; Ottaway, J. M.
A square-wave wavelength modulation system, based on a rotating quartz chopper with four quadrants of different thicknesses, has been developed and evaluated as a method for automatic background correction in carbon furnace atomic emission spectrometry. Accurate background correction is achieved for the residual black body radiation (Rayleigh scatter) from the tube wall and Mie scatter from particles generated by a sample matrix and formed by condensation of atoms in the optical path. Intensity modulation caused by overlap at the edges of the quartz plates and by the divergence of the optical beam at the position of the modulation chopper has been investigated and is likely to be small.
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Atmospheric monitoring in MAGIC and data corrections
NASA Astrophysics Data System (ADS)
Fruck, Christian; Gaug, Markus
2015-03-01
A method for analyzing returns of a custom-made "micro"-LIDAR system, operated alongside the two MAGIC telescopes is presented. This method allows for calculating the transmission through the atmospheric boundary layer as well as thin cloud layers. This is achieved by applying exponential fits to regions of the back-scattering signal that are dominated by Rayleigh scattering. Making this real-time transmission information available for the MAGIC data stream allows to apply atmospheric corrections later on in the analysis. Such corrections allow for extending the effective observation time of MAGIC by including data taken under adverse atmospheric conditions. In the future they will help reducing the systematic uncertainties of energy and flux.
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Allers, Carolina; Sierralta, Walter D; Neubauer, Sonia; Rivera, Francisco; Minguell, José J; Conget, Paulette A
2004-08-27
The use of mesenchymal stem cells (MSC) for cell therapy relies on their capacity to engraft and survive long-term in the appropriate target tissue(s). Animal models have demonstrated that the syngeneic or xenogeneic transplantation of MSC results in donor engraftment into the bone marrow and other tissues of conditioned recipients. However, there are no reliable data showing the fate of human MSC infused into conditioned or unconditioned adult recipients. In the present study, the authors investigated, by using imaging, polymerase chain reaction (PCR), and in situ hybridization, the biodistribution of human bone marrow-derived MSC after intravenous infusion into unconditioned adult nude mice. As assessed by imaging (gamma camera), PCR, and in situ hybridization analysis, the authors' results demonstrate the presence of human MSC in bone marrow, spleen, and mesenchymal tissues of recipient mice. These results suggest that human MSC transplantation into unconditioned recipients represents an option for providing cellular therapy and avoids the complications associated with drugs or radiation conditioning.
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Mesenchymal stem cell mechanobiology and emerging experimental platforms
MacQueen, Luke; Sun, Yu; Simmons, Craig A.
2013-01-01
Experimental control over progenitor cell lineage specification can be achieved by modulating properties of the cell's microenvironment. These include physical properties of the cell adhesion substrate, such as rigidity, topography and deformation owing to dynamic mechanical forces. Multipotent mesenchymal stem cells (MSCs) generate contractile forces to sense and remodel their extracellular microenvironments and thereby obtain information that directs broad aspects of MSC function, including lineage specification. Various physical factors are important regulators of MSC function, but improved understanding of MSC mechanobiology requires novel experimental platforms. Engineers are bridging this gap by developing tools to control mechanical factors with improved precision and throughput, thereby enabling biological investigation of mechanics-driven MSC function. In this review, we introduce MSC mechanobiology and review emerging cell culture platforms that enable new insights into mechanobiological control of MSCs. Our main goals are to provide engineers and microtechnology developers with an up-to-date description of MSC mechanobiology that is relevant to the design of experimental platforms and to introduce biologists to these emerging platforms. PMID:23635493
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A microbial "bloom" at the onset of the Messinian Salinity Crisis in the Piedmont Basin (NW Italy)
NASA Astrophysics Data System (ADS)
Natalicchio, Marcello; Birgel, Daniel; Dela Pierre, Francesco; Lozar, Francesca; Liu, Xiaolei; Hinrichs, Kai-Uwe; Peckmann, Jörn
2015-04-01
The Messinian Salinity Crisis (MSC), a severe ecological crisis that occurred in the Mediterranean Basin about 6 myr ago, had drastic consequences for both freshwater and marine ecosystems (Roveri et al., 2014). The response of prokaryotes to the changing conditions at the MSC onset is virtually unknown. In a lipid biomarker study of sediments straddling the MSC onset from the Pollenzo section (NW Italy), we aim to evaluate the response of microbial communities at the transition from normal marine to extreme conditions. In this section, the advent of the MSC does not coincide with the deposition of gypsum; instead shales and intercalated carbonate-rich beds deposited. These deposits are considered as the deep water counterparts of gypsum layers that formed in the shallower parts of the basin (Dela Pierre et al., 2012). In both pre-MSC and MSC deposits, the molecular fossil inventory is sourced from all three domains of life and is mainly represented by isoprenoidal alcohols, fatty acids, sterols, long chain n-alkanes and n-alcohols. However, after the MSC onset, a sharp increase of the long chains n-alkanes, n-alcohols and fatty acids occurs, indicating a significant increase of terrigenous organic matter, most likely sourced by enhanced riverine runoff. Remarkably, this coincides with an increase of sterols (sitosterol and dinosterol), that are typically interpreted as markers of phytoplankton. The same strata contain filamentous fossils, which have been interpreted as remains of sulfide-oxidizing bacteria (cf., Dela Pierre et al., 2012). The basal MSC deposits are also typified by an increase of isoprenoidal alcohols, including glycerol dibiphytanyl glycerol tetraethers (GDGTs) and diphytanyl glycerol diethers (DGD). Caldarchaeol and crenarchaeol are the overall most abundant GDGTs. Their almost equal distribution in pre-MSC deposits suggests that they derived from planktic Thaumarchaeota, which are abundant picoplanktonic organisms in modern oceans. In contrast, caldarchaeol predominates over crenarchaeol in the MSC deposits, indicating a change towards harsh environmental conditions. A prominent spread of δ13C values between caldarchaeol- and crenarchaeol-derived biphytanes (Δδ13C: 9) in the MSC deposits agrees with a profound modification of the archaeal community structure. This is further confirmed by the sharp increase of the DGD archaeol and the appearance of the DGD extended archaeol. The latter is only sourced by halophilic archaea, confirming an increase of seawater salinity after the MSC onset. In conclusion, this study reveals that lipid biomarkers are excellent recorders of the MSC onset. Moreover, they help to reconstruct the Messinian microbial ecosystems in the course of changing environmental conditions. References Dela Pierre, F., et al., 2012. Palaeogeography, Palaeoclimatology, Palaeoecology 344/345, 78-93. Roveri et al., 2014. Marine Geology 352, 25-58.
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Desjarlais, Michael P.; Scullard, Christian R.; Benedict, Lorin X.; ...
2017-03-13
We compute electrical and thermal conductivities of hydrogen plasmas in the non-degenerate regime using Kohn-Sham Density Functional Theory (DFT) and an application of the Kubo- Greenwood response formula, and demonstrate that for thermal conductivity, the mean-field treatment of the electron-electron (e-e) interaction therein is insufficient to reproduce the weak-coupling limit obtained by plasma kinetic theories. An explicit e-e scattering correction to the DFT is posited by appealing to Matthiessen's Rule and the results of our computations of conductivities with the quantum Lenard-Balescu (QLB) equation. Further motivation of our correction is provided by an argument arising from the Zubarev quantum kineticmore » theory approach. Significant emphasis is placed on our efforts to produce properly converged results for plasma transport using Kohn-Sham DFT, so that an accurate assessment of the importance and efficacy of our e-e scattering corrections to the thermal conductivity can be made.« less
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Dose and scatter characteristics of a novel cone beam CT system for musculoskeletal extremities
NASA Astrophysics Data System (ADS)
Zbijewski, W.; Sisniega, A.; Vaquero, J. J.; Muhit, A.; Packard, N.; Senn, R.; Yang, D.; Yorkston, J.; Carrino, J. A.; Siewerdsen, J. H.
2012-03-01
A novel cone-beam CT (CBCT) system has been developed with promising capabilities for musculoskeletal imaging (e.g., weight-bearing extremities and combined radiographic / volumetric imaging). The prototype system demonstrates diagnostic-quality imaging performance, while the compact geometry and short scan orbit raise new considerations for scatter management and dose characterization that challenge conventional methods. The compact geometry leads to elevated, heterogeneous x-ray scatter distributions - even for small anatomical sites (e.g., knee or wrist), and the short scan orbit results in a non-uniform dose distribution. These complex dose and scatter distributions were investigated via experimental measurements and GPU-accelerated Monte Carlo (MC) simulation. The combination provided a powerful basis for characterizing dose distributions in patient-specific anatomy, investigating the benefits of an antiscatter grid, and examining distinct contributions of coherent and incoherent scatter in artifact correction. Measurements with a 16 cm CTDI phantom show that the dose from the short-scan orbit (0.09 mGy/mAs at isocenter) varies from 0.16 to 0.05 mGy/mAs at various locations on the periphery (all obtained at 80 kVp). MC estimation agreed with dose measurements within 10-15%. Dose distribution in patient-specific anatomy was computed with MC, confirming such heterogeneity and highlighting the elevated energy deposition in bone (factor of ~5-10) compared to soft-tissue. Scatter-to-primary ratio (SPR) up to ~1.5-2 was evident in some regions of the knee. A 10:1 antiscatter grid was found earlier to result in significant improvement in soft-tissue imaging performance without increase in dose. The results of MC simulations elucidated the mechanism behind scatter reduction in the presence of a grid. A ~3-fold reduction in average SPR was found in the MC simulations; however, a linear grid was found to impart additional heterogeneity in the scatter distribution, mainly due to the increase in the contribution of coherent scatter with increased spatial variation. Scatter correction using MC-generated scatter distributions demonstrated significant improvement in cupping and streaks. Physical experimentation combined with GPU-accelerated MC simulation provided a sophisticated, yet practical approach in identifying low-dose acquisition techniques, optimizing scatter correction methods, and evaluating patientspecific dose.
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Arya, Rector; Farook, Vidya S; Fowler, Sharon P; Puppala, Sobha; Chittoor, Geetha; Resendez, Roy G; Mummidi, Srinivas; Vanamala, Jairam; Almasy, Laura; Curran, Joanne E; Comuzzie, Anthony G; Lehman, Donna M; Jenkinson, Christopher P; Lynch, Jane L; DeFronzo, Ralph A; Blangero, John; Hale, Daniel E; Duggirala, Ravindranath; Diego, Vincent P
2018-06-01
Knowledge on genetic and environmental (G × E) interaction effects on cardiometabolic risk factors (CMRFs) in children is limited. The purpose of this study was to examine the impact of G × E interaction effects on CMRFs in Mexican American (MA) children (n = 617, ages 6-17 years). The environments examined were sedentary activity (SA), assessed by recalls from "yesterday" (SAy) and "usually" (SAu) and physical fitness (PF) assessed by Harvard PF scores (HPFS). CMRF data included body mass index (BMI), waist circumference (WC), fat mass (FM), fasting insulin (FI), homeostasis model of assessment-insulin resistance (HOMA-IR), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), systolic (SBP) and diastolic (DBP) blood pressure, and number of metabolic syndrome components (MSC). We examined potential G × E interaction in the phenotypic expression of CMRFs using variance component models and likelihood-based statistical inference. Significant G × SA interactions were identified for six CMRFs: BMI, WC, FI, HOMA-IR, MSC, and HDL, and significant G × HPFS interactions were observed for four CMRFs: BMI, WC, FM, and HOMA-IR. However, after correcting for multiple hypothesis testing, only WC × SAy, FM × SAy, and FI × SAu interactions became marginally significant. After correcting for multiple testing, most of CMRFs exhibited significant G × E interactions (Reduced G × E model vs. Constrained model). These findings provide evidence that genetic factors interact with SA and PF to influence variation in CMRFs, and underscore the need for better understanding of these relationships to develop strategies and interventions to effectively reduce or prevent cardiometabolic risk in children. © 2018 WILEY PERIODICALS, INC.
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Long, Teng; Zhu, Zhenan; Awad, Hani A; Schwarz, Edward M; Hilton, Matthew J; Dong, Yufeng
2014-03-01
Structural bone allografts are widely used in the clinic to treat critical sized bone defects, despite lacking the osteoinductive characteristics of live autografts. To address this, we generated revitalized structural allografts wrapped with mesenchymal stem/progenitor cell (MSC) sheets, which were produced by expanding primary syngenic bone marrow derived cells on temperature-responsive plates, as a tissue-engineered periosteum. In vitro assays demonstrated maintenance of the MSC phenotype in the sheets, suggesting that short-term culturing of MSC sheets is not detrimental. To test their efficacy in vivo, allografts wrapped with MSC sheets were transplanted into 4-mm murine femoral defects and compared to allografts with direct seeding of MSCs and allografts without cells. Evaluations consisted of X-ray plain radiography, 3D microCT, histology, and biomechanical testing at 4- and 6-weeks post-surgery. Our findings demonstrate that MSC sheets induce prolonged cartilage formation at the graft-host junction and enhanced bone callus formation, as well as graft-host osteointegration. Moreover, a large periosteal callus was observed spanning the allografts with MSC sheets, which partially mimics live autograft healing. Finally, biomechanical testing showed a significant increase in the structural and functional properties of MSC sheet grafted femurs. Taken together, MSC sheets exhibit enhanced osteogenicity during critical sized bone defect repair, demonstrating the feasibility of this tissue engineering solution for massive allograft healing. Copyright © 2013 Elsevier Ltd. All rights reserved.
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Voswinkel, Jan; Francois, Sabine; Gorin, Norbert-Claude; Chapel, Alain
2013-07-01
Mesenchymal stromal cells (MSC) are multipotent adult stem cells with the potential to regenerate tissue damage and inhibit inflammation and fibrosis in parallel. As they are non-immunogenic, MSC can be safely auto- and allotransplanted and consequently represent a therapeutic option for refractory connective tissue diseases and fistulizing colitis like Crohn's disease. Actually, there are more than 200 registered clinical trial sites for evaluating MSC therapy, 22 are on autoimmune diseases and 27 are actually recruiting bowel disease' patients. More than 1,500 patients with bowel diseases like Crohn's disease were treated in clinical trials by local as well as systemic MSC therapy. Phase I and II trials on fistula documented the feasibility and safety of MSC therapy, and a significant superiority compared to fibrin glue in fistulizing bowel diseases was demonstrated. Autologous as well as allogeneic use of Bone marrow as well as of adipose tissue-derived MSC are feasible. In refractory Graft versus host disease, especially in refractory gut Graft versus host diseases, encouraging results were reported using MSC. Systemic MSC therapy of refractory irradiation-induced colitis was safe and effective on pain, diarrhea, hemorrhage, inflammation and fistulization accompanied by modulation of the lymphocyte subsets toward an increase in T regulatory cells and a decrease in activated effector T cells. Mesenchymal stem cells represent a safe therapy for patients with refractory inflammatory bowel diseases.
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Gubar, O S; Rodnichenko, A E; Vasyliev, R G; Zlatska, A V; Zubov, D O
2017-09-01
We aimed to isolate and characterize the cell types which could be obtained from postnatal extra-embryonic tissues. Fresh tissues (no more than 12 h after delivery) were used for enzymatic or explants methods of cell isolation. Obtained cultures were further maintained at 5% oxygen. At P3 cell phenotype was assessed by fluorescence-activated cell sorting, population doubling time was calculated and the multilineage differentiation assay was performed. We have isolated multiple cell types from postnatal tissues. Namely, placental mesenchymal stromal cells from placenta chorionic disc, chorionic membrane mesenchymal stromal cells (ChM-MSC) from free chorionic membrane, umbilical cord MSC (UC-MSC) from whole umbilical cord, human umbilical vein endothelial cells (HUVEC) from umbilical vein, amniotic epithelial cells (AEC) and amniotic MSC (AMSC) from amniotic membrane. All isolated cell types displayed high proliferation rate together with the typical MSC phenotype: CD73 + CD90 + CD105 + CD146 + CD166+CD34 - CD45 - HLA-DR - . HUVEC constitutively expressed key markers CD31 and CD309. Most MSC and AEC were capable of osteogenic and adipogenic differentiation. We have shown that a wide variety of cell types can be easily isolated from extra-embryonic tissues and expanded ex vivo for regenerative medicine applications. These cells possess typical MSC properties and can be considered an alternative for adult MSC obtained from bone marrow or fat, especially for allogeneic use.
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NASA Astrophysics Data System (ADS)
Yong, Sang-Soon; Ra, Sung-Woong
2007-10-01
Multi-Spectral Camera(MSC) is a main payload on the KOMPSAT-2 satellite to perform the earth remote sensing. The MSC instrument has one(1) channel for panchromatic imaging and four(4) channel for multi-spectral imaging covering the spectral range from 450nm to 900nm using TDI CCD Focal Plane Array (FPA). The instrument images the earth using a push-broom motion with a swath width of 15 km and a ground sample distance (GSD) of 1 m over the entire field of view (FOV) at altitude 685 Km. The instrument is designed to have an on-orbit operation duty cycle of 20% over the mission lifetime of 3 years with the functions of programmable gain/ offset and on-board image data compression/ storage. The compression method on KOMPSAT-2 MSC was selected and used to match EOS input rate and PDTS output data rate on MSC image data chain. At once the MSC performance was carefully handled to minimize any degradation so that it was analyzed and restored in KGS(KOMPSAT Ground Station) during LEOP and Cal./Val.(Calibration and Validation) phase. In this paper, on-orbit image data chain in MSC and image data processing on KGS including general MSC description is briefly described. The influences on image performance between on-board compression algorithms and between performance restoration methods in ground station are analyzed, and the relation between both methods is to be analyzed and discussed.
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Dashtdar, Havva; Murali, Malliga Raman; Abbas, Azlina Amir; Suhaeb, Abdulrazzaq Mahmod; Selvaratnam, Lakshmi; Tay, Liang Xin; Kamarul, Tunku
2015-05-01
To investigate whether mesenchymal stem cells (MSCs) seeded in novel polyvinyl alcohol (PVA)-chitosan composite hydrogel can provide comparable or even further improve cartilage repair outcomes as compared to previously established alginate-transplanted models. Medial femoral condyle defect was created in both knees of twenty-four mature New Zealand white rabbits, and the animals were divided into four groups containing six animals each. After 3 weeks, the right knees were transplanted with PVA-chitosan-MSC, PVA-chitosan scaffold alone, alginate-MSC construct or alginate alone. The left knee was kept as untreated control. Animals were killed at the end of 6 months after transplantation, and the cartilage repair was assessed through Brittberg morphological score, histological grading by O'Driscoll score and quantitative glycosaminoglycan analysis. Morphological and histological analyses showed significant (p < 0.05) tissue repair when treated with PVA-chitosan-MSC or alginate MSC as compared to the scaffold only and untreated control. In addition, safranin O staining and the glycosaminoglycan (GAG) content were significantly higher (p < 0.05) in MSC treatment groups than in scaffold-only or untreated control group. No significant difference was observed between the PVA-chitosan-MSC- and alginate-MSC-treated groups. PVA-chitosan hydrogel seeded with mesenchymal stem cells provides comparable treatment outcomes to that of previously established alginate-MSC construct implantation. This study supports the potential use of PVA-chitosan hydrogel seeded with MSCs for clinical use in cartilage repair such as traumatic injuries.
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Zhou, Hao; Li, Dandan; Shi, Chen; Xin, Ting; Yang, Junjie; Zhou, Ying; Hu, Shunyin; Tian, Feng; Wang, Jing; Chen, Yundai
2015-01-01
Mesenchymal stem cells (MSC) are regarded as an attractive source of therapeutic stem cells for myocardial infarction. However, their limited self-renewal capacity, low migration capacity and poor viability after transplantation hamper the clinical use of MSC; thus, a strategy to enhance the biological functions of MSC is required. Exendin-4 (Ex-4), a glucagon-like peptide-1 receptor agonist, exerts cell-protective effects on many types of cells. However, little information is available regarding the influence of Ex-4 on MSC. In our study, MSC were isolated from bone marrow and cultured in vitro. After treatment with Ex-4, MSC displayed a higher proliferative capacity, increased C-X-C motif receptor 4 (CXCR4) expression and an enhanced migration response. Moreover, in H2O2-induced apoptosis, Ex-4 preserved mitochondrial function through scavenging ROS and balancing the expression of anti- and pro-apoptotic proteins, leading to the inhibition of the mitochondria-dependent cell death pathways and increased cell survival. Moreover, higher phospho-Akt (p-Akt) expression was observed after Ex-4 intervention. However, blockade of the PI3K/Akt pathway with inhibitors suppressed the above cytoprotective effects of Ex-4, suggesting that the PI3K/Akt pathway is partly responsible for Ex-4-mediated MSC growth, mobilization and survival. These findings provide an attractive method of maximizing the effectiveness of MSC-based therapies in clinical applications. PMID:26250571
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Mechanosensitive channels of Escherichia coli: the MscL gene, protein, and activities
NASA Technical Reports Server (NTRS)
Sukharev, S. I.; Blount, P.; Martinac, B.; Kung, C.
1997-01-01
Although mechanosensory responses are ubiquitous and diverse, the molecular bases of mechanosensation in most cases remain mysterious MscL, a mechanosensitive channel of large conductance of Escherichia coli and its bacterial homologues are the first and currently only channel molecules shown to directly sense mechanical stretch of the membrane. In response to the tension conveyed via the lipid bilayer, MscL increases its open probability by several orders of magnitude. In the present review we describe the identification, cloning, and first sets of biophysical and structural data on this simplest mechanosensory molecule. We discovered a 2.5-ns mechanosensitive conductance in giant E. coli spheroplasts. Using chromatographies to enrich the target and patch clamp to assay the channel activity in liposome-reconstituted fractions, we identified the MscL protein and cloned the mscL gene. MscL comprises 136 amino acid residues (15 kDa), with two highly hydrophobic regions, and resides in the inner membrane of the bacterium. PhoA-fusion experiments indicate that the protein spans the membrane twice with both termini in the cytoplasm. Spectroscopic techniques show that it is highly helical. Expression of MscL tandems and covalent cross-linking suggest that the active channel complex is a homo-hexamer. We have identified several residues, which when deleted or substituted, affect channel kinetics or mechanosensitivity. Although unique when discovered, highly conserved MscL homologues in both gram-negative and gram-positive bacteria have been found, suggesting their ubiquitous importance among bacteria.
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Sui, Bing-Dong; Hu, Cheng-Hu; Zheng, Chen-Xi; Shuai, Yi; He, Xiao-Ning; Gao, Ping-Ping; Zhao, Pan; Li, Meng; Zhang, Xin-Yi; He, Tao; Xuan, Kun; Jin, Yan
2017-01-01
Therapeutic effects of mesenchymal stem cell (MSC) infusion have been revealed in various human disorders, but impacts of diseased micro-environments are only beginning to be noticed. Donor diabetic hyperglycemia is reported to impair therapeutic efficacy of stem cells. However, whether recipient diabetic condition also affects MSC-mediated therapy is unknown. We and others have previously shown that MSC infusion could cure osteopenia, particularly in ovariectomized (OVX) mice. Here, we discovered impaired MSC therapeutic effects on osteopenia in recipient type 1 diabetes (T1D). Through intensive glycemic control by daily insulin treatments, therapeutic effects of MSCs on osteopenia were maintained. Interestingly, by only transiently restoration of recipient euglycemia using single insulin injection, MSC infusion could also rescue T1D-induced osteopenia. Conversely, under recipient hyperglycemia induced by glucose injection in OVX mice, MSC-mediated therapeutic effects on osteopenia were diminished. Mechanistically, recipient hyperglycemic micro-environments reduce anti-inflammatory capacity of MSCs in osteoporotic therapy through suppressing MSC interaction with T cells via the Adenosine monophosphate-activated protein kinase (AMPK) pathway. We further revealed in diabetic micro-environments, double infusion of MSCs ameliorated osteopenia by anti-inflammation, attributed to the first transplanted MSCs which normalized the recipient glucose homeostasis. Collectively, our findings uncover a previously unrecognized role of recipient glycemic conditions controlling MSC-mediated therapy, and unravel that fulfillment of potent therapeutic effects of MSCs requires tight control of recipient micro-environments. PMID:28435461
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Combined Henyey-Greenstein and Rayleigh phase function.
Liu, Quanhua; Weng, Fuzhong
2006-10-01
The phase function is an important parameter that affects the distribution of scattered radiation. In Rayleigh scattering, a scatterer is approximated by a dipole, and its phase function is analytically related to the scattering angle. For the Henyey-Greenstein (HG) approximation, the phase function preserves only the correct asymmetry factor (i.e., the first moment), which is essentially important for anisotropic scattering. When the HG function is applied to small particles, it produces a significant error in radiance. In addition, the HG function is applied only for an intensity radiative transfer. We develop a combined HG and Rayleigh (HG-Rayleigh) phase function. The HG phase function plays the role of modulator extending the application of the Rayleigh phase function for small asymmetry scattering. The HG-Rayleigh phase function guarantees the correct asymmetry factor and is valid for a polarization radiative transfer. It approaches the Rayleigh phase function for small particles. Thus the HG-Rayleigh phase function has wider applications for both intensity and polarimetric radiative transfers. For microwave radiative transfer modeling in this study, the largest errors in the brightness temperature calculations for weak asymmetry scattering are generally below 0.02 K by using the HG-Rayleigh phase function. The errors can be much larger, in the 1-3 K range, if the Rayleigh and HG functions are applied separately.
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NASA Technical Reports Server (NTRS)
Flesia, C.; Schwendimann, P.
1992-01-01
The contribution of the multiple scattering to the lidar signal is dependent on the optical depth tau. Therefore, the radar analysis, based on the assumption that the multiple scattering can be neglected is limited to cases characterized by low values of the optical depth (tau less than or equal to 0.1) and hence it exclude scattering from most clouds. Moreover, all inversion methods relating lidar signal to number densities and particle size must be modified since the multiple scattering affects the direct analysis. The essential requests of a realistic model for lidar measurements which include the multiple scattering and which can be applied to practical situations follow. (1) Requested are not only a correction term or a rough approximation describing results of a certain experiment, but a general theory of multiple scattering tying together the relevant physical parameter we seek to measure. (2) An analytical generalization of the lidar equation which can be applied in the case of a realistic aerosol is requested. A pure analytical formulation is important in order to avoid the convergency and stability problems which, in the case of numerical approach, are due to the large number of events that have to be taken into account in the presence of large depth and/or a strong experimental noise.
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Image Reconstruction for a Partially Collimated Whole Body PET Scanner
Alessio, Adam M.; Schmitz, Ruth E.; MacDonald, Lawrence R.; Wollenweber, Scott D.; Stearns, Charles W.; Ross, Steven G.; Ganin, Alex; Lewellen, Thomas K.; Kinahan, Paul E.
2008-01-01
Partially collimated PET systems have less collimation than conventional 2-D systems and have been shown to offer count rate improvements over 2-D and 3-D systems. Despite this potential, previous efforts have not established image-based improvements with partial collimation and have not customized the reconstruction method for partially collimated data. This work presents an image reconstruction method tailored for partially collimated data. Simulated and measured sensitivity patterns are presented and provide a basis for modification of a fully 3-D reconstruction technique. The proposed method uses a measured normalization correction term to account for the unique sensitivity to true events. This work also proposes a modified scatter correction based on simulated data. Measured image quality data supports the use of the normalization correction term for true events, and suggests that the modified scatter correction is unnecessary. PMID:19096731
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Image Reconstruction for a Partially Collimated Whole Body PET Scanner.
Alessio, Adam M; Schmitz, Ruth E; Macdonald, Lawrence R; Wollenweber, Scott D; Stearns, Charles W; Ross, Steven G; Ganin, Alex; Lewellen, Thomas K; Kinahan, Paul E
2008-06-01
Partially collimated PET systems have less collimation than conventional 2-D systems and have been shown to offer count rate improvements over 2-D and 3-D systems. Despite this potential, previous efforts have not established image-based improvements with partial collimation and have not customized the reconstruction method for partially collimated data. This work presents an image reconstruction method tailored for partially collimated data. Simulated and measured sensitivity patterns are presented and provide a basis for modification of a fully 3-D reconstruction technique. The proposed method uses a measured normalization correction term to account for the unique sensitivity to true events. This work also proposes a modified scatter correction based on simulated data. Measured image quality data supports the use of the normalization correction term for true events, and suggests that the modified scatter correction is unnecessary.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Shen, S; Meredith, R; Azure, M
Purpose: To support the phase I trial for toxicity, biodistribution and pharmacokinetics of intra-peritoneal (IP) 212Pb-TCMC-trastuzumab in patients with HER-2 expressing malignancy. A whole body gamma camera imaging method was developed for estimating amount of 212Pb-TCMC-trastuzumab left in the peritoneal cavity. Methods: {sup 212}Pb decays to {sup 212}Bi via beta emission. {sup 212}Bi emits an alpha particle at an average of 6.1 MeV. The 238.6 keV gamma ray with a 43.6% yield can be exploited for imaging. Initial phantom was made of saline bags with 212Pb. Images were collected for 238.6 keV with a medium energy general purpose collimator. Theremore » are other high energy gamma emissions (e.g. 511keV, 8%; 583 keV, 31%) that penetrate the septae of the collimator and contribute scatter into 238.6 keV. An upper scatter window was used for scatter correction for these high energy gammas. Results: A small source containing 212Pb can be easily visualized. Scatter correction on images of a small 212Pb source resulted in a ∼50% reduction in the full width at tenth maximum (FWTM), while change in full width at half maximum (FWHM) was <10%. For photopeak images, substantial scatter around phantom source extended to > 5 cm outside; scatter correction improved image contrast by removing this scatter around the sources. Patient imaging, in the 1st cohort (n=3) showed little redistribution of 212Pb-TCMC-trastuzumab out of the peritoneal cavity. Compared to the early post-treatment images, the 18-hour post-injection images illustrated the shift to more uniform anterior/posterior abdominal distribution and the loss of intensity due to radioactive decay. Conclusion: Use of medium energy collimator, 15% width of 238.6 keV photopeak, and a 7.5% upper scatter window is adequate for quantification of 212Pb radioactivity inside peritoneal cavity for alpha radioimmunotherapy of ovarian cancer. Research Support: AREVA Med, NIH 1UL1RR025777-01.« less
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Integrated Design and Analysis Tools for Reduced Weight, Affordable Fiber Steered Composites
2004-09-15
110 3.3.5 FEA Package: MSC/PATRAN and MSC/ NASTRAN ...3.10 APPENDIX D: FIBER STEERING CONCEPTUAL DESIGN OF PRELIMINARY STUDIES USING MSC/ NASTRAN SOL 200...and Boundary Conditions ......................................................... 366 Figure 5.3.10 Nastran Analysis Results for Off-Axis Flaws
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Mesenchymal Stem Cells Stabilize Atherosclerotic Vulnerable Plaque by Anti-Inflammatory Properties.
Wang, Shuang-shuang; Hu, Si-wang; Zhang, Qing-hua; Xia, Ai-xiang; Jiang, Zhi-xin; Chen, Xiao-min
2015-01-01
Formation and progression of atherosclerotic vulnerable plaque (VP) is the primary cause of many cardio-cerebrovascular diseases such as acute coronary syndrome and stroke. It has been reported that bone marrow mesenchymal stem cells (MSC) exhibit protective effects against many kinds of diseases including myocardial infarction. Here, we examined the effects of intravenous MSC infusion on a VP model and provide novel evidence of its influence as a therapy in this animal disease model. Thirty healthy male New Zealand white rabbits were randomly divided into a MSC, VP or stable plaque (SP) group (n = 10/group) and received high fat diet and cold-induced common carotid artery intimal injury with liquid nitrogen to form atherosclerotic plaques. Serum hs-CRP, TNF-α, IL-6 and IL-10 levels were measured by ELISA at 1, 2, 3, 7, 14, 21 and 28 days after MSC transplantation. The animals were sacrificed at 4 weeks after MSC transplantation. Lesions in the right common carotid were observed using H&E and Masson staining, and the fibrous cap/lipid core ratio of atherosclerotic plaques were calculated. The expression of nuclear factor κB (NF-κB) and matrix metalloproteinase 1, 2, 9 (MMP-1,2,9) in the plaque were detected using immunohistochemistry, and apoptotic cells in the plaques were detected by TUNEL. In addition, the level of TNF-α stimulated gene/protein 6 (TSG-6) mRNA and protein were measured by quantitative Real-Time PCR and Western blotting, respectively. Two rabbits in the VP group died of lung infection and cerebral infarction respectively at 1 week after plaque injury by liquid nitrogen. Both H&E and Masson staining revealed that the plaques from the SP and MSC groups had more stable morphological structure and a larger fibrous cap/lipid core ratio than the VP group. Serum hs-CRP, TNF-α and IL-6 were significantly down-regulated, whereas IL-10 was significantly up-regulated in the MSC group compared with the VP group. .Immunohistochemistry analysis revealed that NF-κB and MMP expression was reduced in the MSC and SP groups compared to the VP group. Cell apoptosis decreased significantly in both the MSC and SP groups in comparison to the VP group. TSG-6 mRNA and protein expression were higher in the plaques of the MSC group compared to the VP and SP groups. Our study results suggest that MSC transplantation can effectively stabilize vulnerable plaques in atherosclerotic rabbits. This may potentially offer a new clinical application of MSC in atherosclerosis.
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Evaluation of atmospheric correction algorithms for processing SeaWiFS data
NASA Astrophysics Data System (ADS)
Ransibrahmanakul, Varis; Stumpf, Richard; Ramachandran, Sathyadev; Hughes, Kent
2005-08-01
To enable the production of the best chlorophyll products from SeaWiFS data NOAA (Coastwatch and NOS) evaluated the various atmospheric correction algorithms by comparing the satellite derived water reflectance derived for each algorithm with in situ data. Gordon and Wang (1994) introduced a method to correct for Rayleigh and aerosol scattering in the atmosphere so that water reflectance may be derived from the radiance measured at the top of the atmosphere. However, since the correction assumed near infrared scattering to be negligible in coastal waters an invalid assumption, the method over estimates the atmospheric contribution and consequently under estimates water reflectance for the lower wavelength bands on extrapolation. Several improved methods to estimate near infrared correction exist: Siegel et al. (2000); Ruddick et al. (2000); Stumpf et al. (2002) and Stumpf et al. (2003), where an absorbing aerosol correction is also applied along with an additional 1.01% calibration adjustment for the 412 nm band. The evaluation show that the near infrared correction developed by Stumpf et al. (2003) result in an overall minimum error for U.S. waters. As of July 2004, NASA (SEADAS) has selected this as the default method for the atmospheric correction used to produce chlorophyll products.
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Code of Federal Regulations, 2010 CFR
2010-10-01
... Business Management Directorate, MSC; or (ii) The Commander, Military Surface Deployment and Distribution... Commander, MSC, through the Contracts and Business Management Directorate, MSC; or (B) The Commander... MANAGEMENT TRANSPORTATION Ocean Transportation by U.S.-Flag Vessels 247.573-1 Ocean transportation incidental...
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NASA Astrophysics Data System (ADS)
Hidayat, Dony; Istiyanto, Jos; Agus Sumarsono, Danardono
2018-04-01
Loads at main landing gear while touchdown impact is function of aircraft weight and ground reaction load factor. In regulation states ground reaction load factor at Vsink = 3.05 m/s is below 3. Contact/impact force from simulation using MSC ADAMS is 94680 N, while using Solidworks Motion Analysis is 97691 N. The difference between MSC ADAMS and Solidworks Motion Analysis is 3.08%. The ground reaction load factor in MSC ADAMS is 2.78 while in Solidworks Motion Analysis is 2.87.
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MISSION CONTROL CENTER (MCC) VIEW - CONCLUSION APOLLO 11 CELEBRATION - MSC
1969-07-24
S69-40024 (24 July 1969) --- NASA and Manned Spacecraft Center (MSC) officials join in with the flight controllers, in the Mission Operations Control Room (MOCR) in the Mission Control Center (MCC), in celebrating the successful conclusion of the Apollo 11 lunar landing mission. Identifiable in the picture, starting in foreground, are Dr. Robert R. Gilruth, MSC Director; George M. Low, Manager, Apollo Spacecraft Program, MSC; Dr. Christopher C. Kraft Jr., MSC Director of Flight Operation; U.S. Air Force Lt. Gen. Samuel C. Phillips (with glasses, looking downward), Apollo Program Director, Office of Manned Space Flight, NASA Headquarters; and Dr. George E. Mueller (with glasses, looking toward left), Associate Administrator, Office of Manned Space Flight, NASA Headquarters. Former astronaut John H. Glenn Jr. is standing behind Mr. Low.
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Mesenchymal stem cells display hepato-protective activity in lymphoma bearing xenografts.
Secchiero, Paola; Corallini, Federica; Zavan, Barbara; Tripodo, Claudio; Vindigni, Vincenzo; Zauli, Giorgio
2012-04-01
A disseminated model of non-Hodgkin's lymphoma with prevalent liver metastasis was generated by intraperitoneal (i.p.) injection of EBV(+) B lymphoblastoid SKW6.4 in nude-SCID mice. The survival of SKW6.4 xenografts (median survival = 27 days) was significantly improved when hyaluronan scaffolds embedded with mesenchimal stem cells (MSC) were implanted in the abdominal area 4 days after SKW6.4 injection (median survival = 39.5 days). Mice implanted with MSC showed a significant improvement of hepatic functionality in lymphoma xenografts, as demonstrated by measurement of serum ALT/AST levels. Co-culture of MSC with lymphoma cells enhanced the release of hepatocyte growth factor (HGF) by MSC. These data suggest that hyaluronan-embedded MSC exert anti-lymphoma activity by ameliorating hepatic functionality.
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Marrow-derived mesenchymal stem cells: role in epithelial tumor cell determination.
Fierro, Fernando A; Sierralta, Walter D; Epuñan, Maria J; Minguell, José J
2004-01-01
Marrow stroma represents an advantageous environment for development of micrometastatic cells. Within the cellular structure of marrow stroma, mesenchymal stem cells (MSC) have been postulated as an interacting target for disseminated cancer cells. The studies reported here were performed to gain more information on the interaction of the human breast cancer cell line MCF-7 with human bone marrow-derived MSC cells and to investigate whether this interaction affects tumor cell properties. The results showed that after co-culture with MSC, changes were detected in the morphology, proliferative capacity and aggregation pattern of MCF-7 cells, but these parameters were not affected after the co-culture of MSC cells with a non-tumorigenic breast epithelial cell line, MCF-10. Since the indirect culture of MCF-7 with MSC or its products also resulted in functional changes in the tumor cells, we evaluated whether these effects could be attributed to growth factors produced by MSC cells. It was found that VEGF and IL-6 mimic the effects produced by MSC or its products on the proliferation and aggregation properties of MCF-7, cells, respectively. Thus, it seems that after entry of disseminated tumor cells into the marrow space, their proliferative and morphogenetic organization patterns are modified after interaction with distinct stromal cells and/or with specific signals from the marrow microenvironment.
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Finding and tracing human MSC in 3D microenvironments with the photoconvertible protein Dendra2
NASA Astrophysics Data System (ADS)
Caires, Hugo R.; Gomez-Lazaro, Maria; Oliveira, Carla M.; Gomes, David; Mateus, Denisa D.; Oliveira, Carla; Barrias, Cristina C.; Barbosa, Mário A.; Almeida, Catarina R.
2015-05-01
Mesenchymal Stem/Stromal Cells (MSC) are a promising cell type for cell-based therapies - from tissue regeneration to treatment of autoimmune diseases - due to their capacity to migrate to damaged tissues, to differentiate in different lineages and to their immunomodulatory and paracrine properties. Here, a simple and reliable imaging technique was developed to study MSC dynamical behavior in natural and bioengineered 3D matrices. Human MSC were transfected to express a fluorescent photoswitchable protein, Dendra2, which was used to highlight and follow the same group of cells for more than seven days, even if removed from the microscope to the incubator. This strategy provided reliable tracking in 3D microenvironments with different properties, including the hydrogels Matrigel and alginate as well as chitosan porous scaffolds. Comparison of cells mobility within matrices with tuned physicochemical properties revealed that MSC embedded in Matrigel migrated 64% more with 5.2 mg protein/mL than with 9.6 mg/mL and that MSC embedded in RGD-alginate migrated 51% faster with 1% polymer concentration than in 2% RGD-alginate. This platform thus provides a straightforward approach to characterize MSC dynamics in 3D and has applications in the field of stem cell biology and for the development of biomaterials for tissue regeneration.
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Suto, Nana; Mieda, Tokue; Iizuka, Akira; Nakamura, Kazuhiro; Hirai, Hirokazu
2016-08-01
Spinocerebellar ataxia type 1 (SCA1) is caused by the ataxin-1 protein (ATXN1) with an abnormally expanded polyglutamine tract and is characterized by progressive neurodegeneration. We previously showed that intrathecal injection of mesenchymal stem cells (MSCs) during the nonsymptomatic stage mitigates the degeneration of the peripheral nervous system (PNS) neurons in SCA1-knock-in (SCA1-KI) mice. We tested in this study whether the therapeutic effects of MSCs in SCA1-KI mice could be reproduced with MSC-releasing factor(s). To test the effects of MSC-releasing factor(s), we used MSC-conditioned medium (MSC-CM). MSC-CM was intrathecally and/or intravenously injected into young SCA1-KI mice, and the therapeutic effects were assessed in the PNS at later ages using immunostaining, electrophysiology, and behavioral tests. MSC-CM attenuated the degeneration of axons and myelin of spinal motor neurons. Consequently, the injected SCA1-KI mice exhibited smaller reductions in nerve conduction velocity in spinal motor neurons and reduced motor incoordination than the untreated mice. These results suggest that factors released from MSC mitigate the morphological and functional abnormalities in the PNS that are observed in SCA1-KI mice in a paracrine manner. © 2016 John Wiley & Sons Ltd.
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Marini, Irene; Siegemund, Martin; Hutt, Meike; Kontermann, Roland E.; Pfizenmaier, Klaus
2017-01-01
Mesenchymal stem cells (MSCs) are currently exploited as gene delivery systems for transient in situ expression of cancer therapeutics. As an alternative to the prevailing viral expression, we here describe a murine MSC line stably expressing a therapeutic protein for up to 42 passages, yet fully maintaining MSC features. Because of superior antitumoral activity of hexavalent TNF-related apoptosis-inducing ligand (TRAIL) formats and the advantage of a tumor-targeted action, we choose expression of a dimeric EGFR-specific diabody single-chain TRAIL (Db-scTRAIL) as a model. The bioactivity of Db-scTRAIL produced from an isolated clone (MSC.TRAIL) was revealed from cell death induction in Colo205 cells treated with either culture supernatants from or cocultured with MSC.TRAIL. In vivo, therapeutic activity of MSC.TRAIL was shown upon peritumoral injection in a Colo205 xenograft tumor model. Best antitumor activity in vitro and in vivo was observed upon combined treatment of MSC.TRAIL with bortezomib. Importantly, in vivo combination treatment did not cause apparent hepatotoxicity, weight loss, or behavioral changes. The development of well characterized stocks of stable drug-producing human MSC lines has the potential to establish standardized protocols of cell-based therapy broadly applicable in cancer treatment. PMID:28553285
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Brückner, Sandra, E-mail: sandra.brueckner@medizin.uni-leipzig.de; Tautenhahn, Hans-Michael, E-mail: hans-michael.tautenhahn@medizin.uni-leipzig.de; TRM, Translational Centre for Regenerative Medicine, Philipp-Rosenthal-Str. 55, Leipzig D-04103
Study background: Extended liver resection is the only curative treatment option of liver cancer. Yet, the residual liver may not accomplish the high metabolic and regenerative capacity needed, which frequently leads to acute liver failure. Because of their anti-inflammatory and -apoptotic as well as pro-proliferative features, mesenchymal stem cells differentiated into hepatocyte-like cells might provide functional and regenerative compensation. Clinical translation of basic research requires pre-clinical approval in large animals. Therefore, we characterized porcine mesenchymal stem cells (MSC) from adipose tissue and bone marrow and their hepatocyte differentiation potential for future assessment of functional liver support after surgical intervention inmore » the pig model. Methods: Mesenchymal surface antigens and multi-lineage differentiation potential of porcine MSC isolated by collagenase digestion either from bone marrow or adipose tissue (subcutaneous/visceral) were assessed by flow cytometry. Morphology and functional properties (urea-, glycogen synthesis and cytochrome P450 activity) were determined during culture under differentiation conditions and compared with primary porcine hepatocytes. Results: MSC from porcine adipose tissue and from bone marrow express the typical mesenchymal markers CD44, CD29, CD90 and CD105 but not haematopoietic markers. MSC from both sources displayed differentiation into the osteogenic as well as adipogenic lineage. After hepatocyte differentiation, expression of CD105 decreased significantly and cells adopted the typical polygonal morphology of hepatocytes. Glycogen storage was comparable in adipose tissue- and bone marrow-derived cells. Urea synthesis was about 35% lower in visceral than in subcutaneous adipose tissue-derived MSC. Cytochrome P450 activity increased significantly during differentiation and was twice as high in hepatocyte-like cells generated from bone marrow as from adipose tissue. Conclusion: The hepatocyte differentiation of porcine adipose tissue-derived MSC was shown for the first time yielding hepatocyte-like cells with specific functions similar in bone marrow and subcutaneous adipose tissue-derived MSC. That makes them good pre-clinical candidates for supportive approaches after liver resection in the pig. - Highlights: • First time to show hepatocytic differentiation of porcine adipose tissue-derived MSC. • Hepatocytic-differentiated MSC display metabolic qualities of primary hepatocytes. • Metabolic potency varies between differentiated MSC from different tissues. • MSC are good candidates for pre-clinical evaluation of stem cell-based therapies.« less
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Mu, S; Tee, B C; Emam, H; Zhou, Y; Sun, Z
2018-04-06
Impaired bone formation of the buccal alveolar plate after tooth extraction during adolescence increases the difficulty of future implant restoration. This study was undertaken to assess the feasibility and efficacy of transplanting autogenous scaffold-free culture-expanded mesenchymal stem cell (MSC) sheets to the buccal alveolar bone surface to stimulate local bone growth. Mandibular bone marrow was aspirated from 3-month-old pigs (n = 5), from which MSCs were isolated and culture expanded. Triple-layer MSC sheets were then fabricated using temperature-responsive tissue culture plates. One month after bone marrow aspirations, the same pigs underwent bilateral extraction of mandibular primary molars, immediately followed by transplantation of 3 autogenous triple-layer MSC sheets on to the subperiosteal buccal alveolar surface of 1 randomly chosen side. The contralateral side (control) underwent the same periosteal reflection surgery without receiving MSC sheet transplantation. Six weeks later, the animals were killed and specimens from both sides were immediately harvested for radiographic and histological analysis. Buccal alveolar bone thickness, tissue mineral density (TMD), mineral apposition and bone volume fraction (BV/TV) were quantified and compared between the MSC sheet and control sides using paired t-tests. Triple-layer MSC sheets were reliably fabricated and the majority of cells remained vital before transplantation. The thickness of buccal bone tended to increase with MSC sheet transplantation (P = .18), with 4 of 5 animals showing an average of 1.82 ± 0.73 mm thicker bone on the MSC sheet side than the control side. After being normalized by the TMD of intracortical bone, the TMD of surface cortical bone was 0.5-fold higher on the MSC sheet side than the control side (P < .05). Likewise, the BV/TV measurements of the buccal surface region were also 0.4-fold higher on the MSC sheet side than the control side (P < .05) after being normalized by measurements from the intracortical region. Mineral apposition measurements were not different between the 2 sides. Mandibular marrow-derived MSCs can be fabricated into cell sheets and autogenous transplantation of MSC sheets onto the subperiosteal buccal alveolar bone surface at the tooth-extraction site may increase local bone density. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
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Ophelders, Daan R M G; Wolfs, Tim G A M; Jellema, Reint K; Zwanenburg, Alex; Andriessen, Peter; Delhaas, Tammo; Ludwig, Anna-Kristin; Radtke, Stefan; Peters, Vera; Janssen, Leon; Giebel, Bernd; Kramer, Boris W
2016-06-01
Preterm neonates are susceptible to perinatal hypoxic-ischemic brain injury, for which no treatment is available. In a preclinical animal model of hypoxic-ischemic brain injury in ovine fetuses, we have demonstrated the neuroprotective potential of systemically administered mesenchymal stromal cells (MSCs). The mechanism of MSC treatment is unclear but suggested to be paracrine, through secretion of extracellular vesicles (EVs). Therefore, we investigated in this study the protective effects of mesenchymal stromal cell-derived extracellular vesicles (MSC-EVs) in a preclinical model of preterm hypoxic-ischemic brain injury. Ovine fetuses were subjected to global hypoxia-ischemia by transient umbilical cord occlusion, followed by in utero intravenous administration of MSC-EVs. The therapeutic effects of MSC-EV administration were assessed by analysis of electrophysiological parameters and histology of the brain. Systemic administration of MSC-EVs improved brain function by reducing the total number and duration of seizures, and by preserving baroreceptor reflex sensitivity. These functional protections were accompanied by a tendency to prevent hypomyelination. Cerebral inflammation remained unaffected by the MSC-EV treatment. Our data demonstrate that MSC-EV treatment might provide a novel strategy to reduce the neurological sequelae following hypoxic-ischemic injury of the preterm brain. Our study results suggest that a cell-free preparation comprising neuroprotective MSC-EVs could substitute MSCs in the treatment of preterm neonates with hypoxic-ischemic brain injury, thereby circumventing the potential risks of systemic administration of living cells. Bone marrow-derived mesenchymal stromal cells (MSCs) show promise in treating hypoxic-ischemic injury of the preterm brain. Study results suggest administration of extracellular vesicles, rather than intact MSCs, is sufficient to exert therapeutic effects and avoids potential concerns associated with administration of living cells. The therapeutic efficacy of systemically administered mesenchymal stromal cell-derived extracellular vesicles (MSC-EVs) on hypoxia-ischemia-induced injury was assessed in the preterm ovine brain. Impaired function and structural injury of the fetal brain was improved following global hypoxia-ischemia. A cell-free preparation of MSC-EVs could substitute for the cellular counterpart in the treatment of preterm neonates with hypoxic-ischemic brain injury. This may open new clinical applications for "off-the-shelf" interventions with MSC-EVs. ©AlphaMed Press.
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Trzil, Julie E; Masseau, Isabelle; Webb, Tracy L; Chang, Chee-Hoon; Dodam, John R; Liu, Hong; Quimby, Jessica M; Dow, Steven W; Reinero, Carol R
2016-12-01
The aim of this study was to evaluate the feasibility and efficacy of serially administered adipose-derived mesenchymal stem cells (MSCs) in an experimental feline asthma model. Allergic asthma was acutely induced with Bermuda grass allergen in six purpose-bred cats. Five intravenous infusions of allogeneic MSCs (n = 4; MSC-treated) or saline (n = 2; placebo-treated) were administered over the first 130 days after asthma induction. Infusions contained 2 × 10 6 , 4 × 10 6 , 4.7 × 10 6 , 1 × 10 7 and 1 × 10 7 cryopreserved MSCs/cat. For thoracic imaging additional cats were enrolled as control groups: four untreated, experimentally asthmatic cats (combined with placebo-treated cats), and six healthy, non-asthmatic cats. Outcome measures included airway eosinophilia, pulmonary mechanics, thoracic computed tomography and several immunologic assays. Cats were assessed for 9 months after treatment. At early points, airway eosinophil percentage was not affected by MSC administration (post-treatment average of days 12, 26, 47, 108 and 133 in MSC-treated cats was 41 ± 15% and in placebo-treated cats it was 34 ± 16%). By month 9, eosinophil percentages in all MSC-treated cats decreased to normal reference intervals (MSC-treated 6%; placebo-treated 20%; normal <17%). Diminished airway hyper-responsiveness was noted in all MSC-treated compared with placebo-treated cats at day 133 (dose of methacholine to double baseline airway resistance: MSC-treated median 22.9 mg/ml [range 6.4-64.0]; individual placebo-treated cats 1.1 and 5.0 mg/ml). Lung attenuation (mean ± SEM MSC-treated -865 ± 12 Hounsfield units [HU]; untreated asthmatics -820 ± 11 HU; P = 0.004) and bronchial wall thickening scores (median [interquartile range] MSC-treated 0 [0-1.5]; untreated asthmatic 11.6 [7.3-27.3]; P = 0.010) were significantly reduced in MSC-treated vs untreated asthmatic cats, consistent with decreased airway remodeling at month 9. No clear immunologic mechanisms by which MSCs act were determined. MSCs may have a delayed effect in reducing airway inflammation, airway hyper-responsiveness and remodeling in experimentally induced asthmatic cats. Results warrant additional investigation of MSC therapy for asthma in cats. © The Author(s) 2015.
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Transient radiative transfer in a scattering slab considering polarization.
Yi, Hongliang; Ben, Xun; Tan, Heping
2013-11-04
The characteristics of the transient and polarization must be considered for a complete and correct description of short-pulse laser transfer in a scattering medium. A Monte Carlo (MC) method combined with a time shift and superposition principle is developed to simulate transient vector (polarized) radiative transfer in a scattering medium. The transient vector radiative transfer matrix (TVRTM) is defined to describe the transient polarization behavior of short-pulse laser propagating in the scattering medium. According to the definition of reflectivity, a new criterion of reflection at Fresnel surface is presented. In order to improve the computational efficiency and accuracy, a time shift and superposition principle is applied to the MC model for transient vector radiative transfer. The results for transient scalar radiative transfer and steady-state vector radiative transfer are compared with those in published literatures, respectively, and an excellent agreement between them is observed, which validates the correctness of the present model. Finally, transient radiative transfer is simulated considering the polarization effect of short-pulse laser in a scattering medium, and the distributions of Stokes vector in angular and temporal space are presented.
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Effect of Multiple Scattering on the Compton Recoil Current Generated in an EMP, Revisited
Farmer, William A.; Friedman, Alex
2015-06-18
Multiple scattering has historically been treated in EMP modeling through the obliquity factor. The validity of this approach is examined here. A simplified model problem, which correctly captures cyclotron motion, Doppler shifting due to the electron motion, and multiple scattering is first considered. The simplified problem is solved three ways: the obliquity factor, Monte-Carlo, and Fokker-Planck finite-difference. Because of the Doppler effect, skewness occurs in the distribution. It is demonstrated that the obliquity factor does not correctly capture this skewness, but the Monte-Carlo and Fokker-Planck finite-difference approaches do. Here, the obliquity factor and Fokker-Planck finite-difference approaches are then compared inmore » a fuller treatment, which includes the initial Klein-Nishina distribution of the electrons, and the momentum dependence of both drag and scattering. It is found that, in general, the obliquity factor is adequate for most situations. However, as the gamma energy increases and the Klein-Nishina becomes more peaked in the forward direction, skewness in the distribution causes greater disagreement between the obliquity factor and a more accurate model of multiple scattering.« less
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NASA Astrophysics Data System (ADS)
Saturno, Jorge; Pöhlker, Christopher; Massabò, Dario; Brito, Joel; Carbone, Samara; Cheng, Yafang; Chi, Xuguang; Ditas, Florian; Hrabě de Angelis, Isabella; Morán-Zuloaga, Daniel; Pöhlker, Mira L.; Rizzo, Luciana V.; Walter, David; Wang, Qiaoqiao; Artaxo, Paulo; Prati, Paolo; Andreae, Meinrat O.
2017-08-01
Deriving absorption coefficients from Aethalometer attenuation data requires different corrections to compensate for artifacts related to filter-loading effects, scattering by filter fibers, and scattering by aerosol particles. In this study, two different correction schemes were applied to seven-wavelength Aethalometer data, using multi-angle absorption photometer (MAAP) data as a reference absorption measurement at 637 nm. The compensation algorithms were compared to five-wavelength offline absorption measurements obtained with a multi-wavelength absorbance analyzer (MWAA), which serves as a multiple-wavelength reference measurement. The online measurements took place in the Amazon rainforest, from the wet-to-dry transition season to the dry season (June-September 2014). The mean absorption coefficient (at 637 nm) during this period was 1.8 ± 2.1 Mm-1, with a maximum of 15.9 Mm-1. Under these conditions, the filter-loading compensation was negligible. One of the correction schemes was found to artificially increase the short-wavelength absorption coefficients. It was found that accounting for the aerosol optical properties in the scattering compensation significantly affects the absorption Ångström exponent (åABS) retrievals. Proper Aethalometer data compensation schemes are crucial to retrieve the correct åABS, which is commonly implemented in brown carbon contribution calculations. Additionally, we found that the wavelength dependence of uncompensated Aethalometer attenuation data significantly correlates with the åABS retrieved from offline MWAA measurements.
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Liu, Xin
2014-01-01
This study describes a deterministic method for simulating the first-order scattering in a medical computed tomography scanner. The method was developed based on a physics model of x-ray photon interactions with matter and a ray tracing technique. The results from simulated scattering were compared to the ones from an actual scattering measurement. Two phantoms with homogeneous and heterogeneous material distributions were used in the scattering simulation and measurement. It was found that the simulated scatter profile was in agreement with the measurement result, with an average difference of 25% or less. Finally, tomographic images with artifacts caused by scatter were corrected based on the simulated scatter profiles. The image quality improved significantly.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Li, Jing; Chen, Jun; Li, Xiuyu
Stem cell vaccination can induce consistent and strong anti-tumor immunity against cancer in mice model. The antigenic similarity between tumors and embryos has been appreciated for many years and reflects the expression of embryonic gene products by cancer cells and/or cancer-initiating stem cells. Taking advantage of this similarity, we have tested a prophylactic lung cancer vaccine composed of allogeneic murine MSCs. Based on this conception, we first compared their tumor vaccines intervention effects of adult MSCs and MSCs under simulated microgravity (MSC/SMG). In this study, BALB/c mice were vaccinated with MSCs or MSC/SMG, compared with mice vaccinated with phosphate bufferedmore » saline (PBS) as negative controls. We then subcutaneously implanted the A549 human lung cancer cell line into vaccinated mice and monitored tumor growth potential in vivo. The smaller tumor size and less tumor weight were observed in mice vaccinated with MSCs or MSC/SMG, compared with that of the Control group. Particularly, it was much more significant in the group of MSC/SMG than that group of the MSCs. Vaccination with SMG treated MSCs inhibited proliferation and promoted apoptosis of tumor tissue. SMG/MSC vaccination induced bothTh1-mediated cytokine response; CD8-dependent cytotoxic response which reduced the proportion of Treg cells. Furthermore, SMG/MSC vaccination significantly increased MHC1 and HSPs proteins expression. In conclusion, we demonstrated the SMG could improve tumor-suppressive activity of MSC. The enhanced anti-tumor immune response of MSCs/SMG was strongly associated with the higher expression of MHC class I molecule on DCs, and the abundance of HSPs in the SMG treated MSCs may make antigens in the MSC more cross-presentable to the host DCs for generating protective antitumor activity. This study gains an insight into the mechanism of MSCs anti-tumor efficacy and gives a new strategy for cancer therapies in the future. - Highlights: • Vaccination with SMG treated MSCs inhibited tumor growth. • SMG/MSC vaccination induced Th1-mediated cytokine response, elicited CD8-dependent cytotoxic response and reduced the proportion of Treg cells. • SMG/MSC vaccination increased MHC1 and HSPs proteins expression.« less
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Salomon, Carlos; Ryan, Jennifer; Sobrevia, Luis; Kobayashi, Miharu; Ashman, Keith; Mitchell, Murray; Rice, Gregory E.
2013-01-01
Vasculogenesis and angiogenesis are critical processes in fetal circulation and placental vasculature development. Placental mesenchymal stem cells (pMSC) are known to release paracrine factors (some of which are contained within exosomes) that promote angiogenesis and cell migration. The aims of this study were: to determine the effects of oxygen tension on the release of exosomes from pMSC; and to establish the effects of pMSC-derived exosomes on the migration and angiogenic tube formation of placental microvascular endothelial cells (hPMEC). pMSC were isolated from placental villi (8–12 weeks of gestation, n = 6) and cultured under an atmosphere of 1%, 3% or 8% O2. Cell-conditioned media were collected and exosomes (exo-pMSC) isolated by differential and buoyant density centrifugation. The dose effect (5–20 µg exosomal protein/ml) of pMSC-derived exosomes on hPMEC migration and tube formation were established using a real-time, live-cell imaging system (Incucyte™). The exosome pellet was resuspended in PBS and protein content was established by mass spectrometry (MS). Protein function and canonical pathways were identified using the PANTHER program and Ingenuity Pathway Analysis, respectively. Exo-pMSC were identified, by electron microscopy, as spherical vesicles, with a typical cup-shape and diameters around of 100 nm and positive for exosome markers: CD63, CD9 and CD81. Under hypoxic conditions (1% and 3% O2) exo-pMSC released increased by 3.3 and 6.7 folds, respectively, when compared to the controls (8% O2; p<0.01). Exo-pMSC increased hPMEC migration by 1.6 fold compared to the control (p<0.05) and increased hPMEC tube formation by 7.2 fold (p<0.05). MS analysis identified 390 different proteins involved in cytoskeleton organization, development, immunomodulatory, and cell-to-cell communication. The data obtained support the hypothesis that pMSC-derived exosomes may contribute to placental vascular adaptation to low oxygen tension under both physiological and pathological conditions. PMID:23861904
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Zhang, Jia-min; Feng, Fei-er; Wang, Qian-ming; Zhu, Xiao-lu; Fu, Hai-xia; Xu, Lan-ping; Liu, Kai-yan
2016-01-01
Immune thrombocytopenia (ITP) is characterized by platelet destruction and megakaryocyte dysfunction. Mesenchymal stem cells (MSCs) from ITP patients (MSC-ITP) do not exhibit conventional proliferative abilities and thus exhibit defects in immunoregulation, suggesting that MSC impairment might be a mechanism involved in ITP. Platelet-derived growth factor (PDGF) improves growth and survival in various cell types. Moreover, PDGF promotes MSC proliferation. The aim of the present study was to analyze the effects of PDGF-BB on MSC-ITP. We showed that MSC-ITP expanded more slowly and appeared flattened and larger. MSC-ITP exhibited increased apoptosis and senescence compared with controls. Both the intrinsic and extrinsic pathways account for the enhanced apoptosis. P53 and p21 expression were upregulated in MSC-ITP, but inhibition of p53 with pifithrin-α markedly inhibited apoptosis and senescence. Furthermore, MSCs from ITP patients showed a lower capacity for inhibiting the proliferation of activated T cells inducing regulatory T cells (Tregs) and suppressing the synthesis of anti-glycoprotein (GP)IIb-IIIa antibodies. PDGF-BB treatment significantly decreased the expression of p53 and p21 and increased survivin expression in MSC-ITP. In addition, the apoptotic rate and number of senescent cells in ITP MSCs were reduced. Their impaired ability for inhibiting activated T cells, inducing Tregs, and suppressing the synthesis of anti-GPIIb-IIIa antibodies was restored after PDGF-BB treatment. In conclusion, we have demonstrated that PDGF-BB protects MSCs derived from ITP patients against apoptosis, senescence, and immunomodulatory defects. This protective effect of PDGF-BB is likely mediated via the p53/p21 pathway, thus potentially providing a new therapeutic approach for ITP. Significance Immune thrombocytopenia (ITP) is characterized by platelet destruction and megakaryocyte dysfunction. Platelet-derived growth factor (PDGF) improves growth and survival in various cell types and promotes mesenchymal stem cell (MSC) proliferation. PDGF-BB protects MSCs derived from ITP patients against apoptosis, senescence, and immunomodulatory defects. This protective effect of PDGF-BB is likely mediated via the p53/p21 pathway, thus potentially providing a new therapeutic approach for ITP. PMID:27471307
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Magnetic Search Coil (MSC) of Plasma Wave Experiment (PWE) aboard the Arase (ERG) satellite
NASA Astrophysics Data System (ADS)
Ozaki, Mitsunori; Yagitani, Satoshi; Kasahara, Yoshiya; Kojima, Hirotsugu; Kasaba, Yasumasa; Kumamoto, Atsushi; Tsuchiya, Fuminori; Matsuda, Shoya; Matsuoka, Ayako; Sasaki, Takashi; Yumoto, Takahiro
2018-05-01
This paper presents detailed performance values of the Magnetic Search Coil (MSC) that is part of the Plasma Wave Experiment on board the Arase (ERG) satellite. The MSC consists of a three-axis search coil magnetometer with a 200-mm-long magnetic core. The MSC plays a central role in the magnetic field observations, particularly for whistler mode chorus and hiss waves in a few kHz frequency range, which may cause local acceleration and/or rapid loss of radiation belt electrons. Accordingly, the MSC was carefully designed and developed to operate well in harsh radiation environments. To ascertain the wave-normal vectors, polarizations, and refractive indices of the plasma waves in a wide frequency band, the output signals detected by the MSC are fed into the two different wave receivers: one is the WaveForm Capture/Onboard Frequency Analyzer for waveform and spectrum observations in the frequency range from a few Hz up to 20 kHz, and the other is the High Frequency Analyzer for spectrum observations in the frequency range from 10 to 100 kHz. The noise equivalent magnetic induction of the MSC is 20 {fT/Hz}^{1/2} at a frequency of 2 kHz, and the null depth of directionality is - 40 dB, which is equivalent to an angular error less than 1°. The MSC on board the Arase satellite is the first experiment using a current-sensitive preamplifier for probing the plasma waves in the radiation belts.[Figure not available: see fulltext.
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Cardiac mesenchymal stromal cells are a source of adipocytes in arrhythmogenic cardiomyopathy
Sommariva, E.; Brambilla, S.; Carbucicchio, C.; Gambini, E.; Meraviglia, V.; Dello Russo, A.; Farina, F.M.; Casella, M.; Catto, V.; Pontone, G.; Chiesa, M.; Stadiotti, I.; Cogliati, E.; Paolin, A.; Ouali Alami, N.; Preziuso, C.; d'Amati, G.; Colombo, G.I.; Rossini, A.; Capogrossi, M.C.; Tondo, C.; Pompilio, G.
2016-01-01
Abstract Aim Arrhythmogenic cardiomyopathy (ACM) is a genetic disorder mainly due to mutations in desmosomal genes, characterized by progressive fibro-adipose replacement of the myocardium, arrhythmias, and sudden death. It is still unclear which cell type is responsible for fibro-adipose substitution and which molecular mechanisms lead to this structural change. Cardiac mesenchymal stromal cells (C-MSC) are the most abundant cells in the heart, with propensity to differentiate into several cell types, including adipocytes, and their role in ACM is unknown. The aim of the present study was to investigate whether C-MSC contributed to excess adipocytes in patients with ACM. Methods and results We found that, in ACM patients' explanted heart sections, cells actively differentiating into adipocytes are of mesenchymal origin. Therefore, we isolated C-MSC from endomyocardial biopsies of ACM and from not affected by arrhythmogenic cardiomyopathy (NON-ACM) (control) patients. We found that both ACM and control C-MSC express desmosomal genes, with ACM C-MSC showing lower expression of plakophilin (PKP2) protein vs. controls. Arrhythmogenic cardiomyopathy C-MSC cultured in adipogenic medium accumulated more lipid droplets than controls. Accordingly, the expression of adipogenic genes was higher in ACM vs. NON-ACM C-MSC, while expression of cell cycle and anti-adipogenic genes was lower. Both lipid accumulation and transcription reprogramming were dependent on PKP2 deficiency. Conclusions Cardiac mesenchymal stromal cells contribute to the adipogenic substitution observed in ACM patients' hearts. Moreover, C-MSC from ACM patients recapitulate the features of ACM adipogenesis, representing a novel, scalable, patient-specific in vitro tool for future mechanistic studies. PMID:26590176
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Ramos, Teresa L.; Sánchez-Abarca, Luis Ignacio; Redondo, Alba; Hernández-Hernández, Ángel; Almeida, Antonio M.; Puig, Noemí; Rodríguez, Concepción; Ortega, Rebeca; Preciado, Silvia; Rico, Ana; Muntión, Sandra; González Porras, José Ramón; Cañizo, Consuelo Del; Sánchez-Guijo, Fermín
2017-01-01
Histone deacetylases (HDACs) are involved in epigenetic modulation and their aberrant expression has been demonstrated in myeloproliferative neoplasms (MPN). HDAC8 inhibition has been shown to inhibit JAK2/STAT5 signaling in hematopoietic cells from MPN. Nevertheless, the role of HDAC8 expression in bone marrow-mesenchymal stromal cells (BM-MSC) has not been assessed. In the current work we describe that HDAC8 is significantly over-expressed in MSC from in JAK-2 positive MPN compared to those from healthy-donors (HD-MSC). Using a selective HDAC8 inhibitor (PCI34051), we verified that the subsequent decrease in the protein and mRNA expression of HDAC8 is linked with an increased apoptosis of malignant MSC whereas it has no effects on normal MSC. In addition, HDAC8 inhibition in MPN-MSC also decreased their capacity to maintain neoplastic hematopoiesis, by increasing the apoptosis, cell-cycle arrest and colony formation of JAK2+-hematopoietic cells. Mechanistic studies using different MPN cell lines revealed that PCI34051 induced their apoptosis, which is enhanced when were co-cultured with JAK2V617F-MSC, decreased their colony formation and the phosphorylation of STAT3 and STAT5. In summary, we show for the first time that the inhibition of HDAC8 in MSC from JAK2+ MPN patients selectively decreases their hematopoietic-supporting ability, suggesting that HDAC8 may be a potential therapeutic target in this setting by acting not only on hematopoietic cells but also on the malignant microenvironment. PMID:28390197
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EFFECTS OF PLATING DENSITY AND CULTURE TIME ON BONE MARROW STROMAL CELL CHARACTERISTICS
Neuhuber, Birgit; Swanger, Sharon A.; Howard, Linda; Mackay, Alastair; Fischer, Itzhak
2008-01-01
Objective Bone marrow stromal cells (MSC) are multipotent adult stem cells that have emerged as promising candidates for cell therapy in disorders including cardiac infarction, stroke and spinal cord injury. While harvesting methods used by different laboratories are relatively standard, MSC culturing protocols vary widely. This study is aimed at evaluating the effects of initial plating density and total time in culture on proliferation, cell morphology, and differentiation potential of heterogeneous MSC cultures and more homogeneous cloned subpopulations. Methods Rat MSC were plated at 20, 200 and 2000 cells/cm2 and grown to 50% confluency. The numbers of population doublings and doubling times were determined within and across multiple passages. Changes in cell morphology and differentiation potential to adipogenic, chondrogenic, and osteogenic lineages were evaluated and compared among early, intermediate and late passages, as well as between heterogeneous and cloned MSC populations. Results We found optimal cell growth at a plating density of 200 cells/cm2. Cultures derived from all plating densities developed increased proportions of flat cells over time. Assays for chondrogenesis, osteogenesis and adipogenesis showed that heterogeneous MSC plated at all densities sustained the potential for all three mesenchymal phenotypes through at least passage 5; the flat subpopulation lost adipogenic and chondrogenic potential. Conclusion Our findings suggest that the initial plating density is not critical for maintaining a well-defined, multipotent MSC population. Time in culture, however, affects cell characteristics, suggesting that cell expansion should be limited, especially until the specific characteristics of different MSC subpopulations are better understood. PMID:18495329
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The plant homeodomain fingers of fission yeast Msc1 exhibit E3 ubiquitin ligase activity.
Dul, Barbara E; Walworth, Nancy C
2007-06-22
The DNA damage checkpoint pathway governs how cells regulate cell cycle progression in response to DNA damage. A screen for suppressors of a fission yeast chk1 mutant defective in the checkpoint pathway identified a novel Schizosaccharomyces pombe protein, Msc1. Msc1 contains 3 plant homeodomain (PHD) finger motifs, characteristically defined by a C4HC3 consensus similar to RING finger domains. PHD finger domains in viral proteins and in the cellular protein kinase MEKK1 (mitogen-activated protein kinase/extracellular signal-regulated kinase kinase kinase 1) have been implicated as ubiquitin E3 protein ligases that affect protein stability. The close structural relationship of PHD fingers to RING fingers suggests that other PHD domain-containing proteins might share this activity. We show that each of the three PHD fingers of Msc1 can act as ubiquitin E3 ligases, reporting for the first time that PHD fingers from a nuclear protein exhibit E3 ubiquitin ligase activity. The function of the PHD fingers of Msc1 is needed to rescue the DNA damage sensitivity of a chk1Delta strain. Msc1 co-precipitates Rhp6, the S. pombe homologue of the human ubiquitin-conjugating enzyme Ubc2. Strikingly, deletion of msc1 confers complete suppression of the slow growth phenotype, UV and hydroxyurea sensitivities of an rhp6 deletion strain and restores deficient histone H3 methylation observed in the rhp6Delta mutant. We speculate that the target of the E3 ubiquitin ligase activity of Msc1 is likely to be a chromatin-associated protein.
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Zhao, Qinjun; Ren, Hongying; Li, Xiyuan; Chen, Zhong; Zhang, Xiangyu; Gong, Wei; Liu, Yongjun; Pang, Tianxiang; Han, Zhong Chao
2009-01-01
Mesenchymal stromal cells (MSC) isolated from several human tissues have been known to differentiate into the hepatic lineage in vitro, but the immunogenicity of the differentiated hepatocyte-like cells (DHC) has not been reported. Umbilical cord (UC) MSC are thought to be an attractive cell source for cell therapy because of their young age and low infection rate compared with adult tissue MSC. Hepatic differentiation of UC-MSC was induced with a 2-step protocol. The expressions of hepatic markers were detected by RT-PCR and immunofluorescence staining. Albumin production and urea secretion were measured by ELISA and colorimetric assay respectively. The immunosuppressive properties of DHC was detected by mixed lymphocyte culture. After incubation with specific growth factors, including hepatocyte growth factor (HGF) and basic fibroblast growth factor (bFGF), UC MSC exhibited a high hepatic differentiation ability in an adherent culture condition. The differentiated UC MSC showed hepatocyte-like morphology and expressed several liver-specific markers at gene and protein levels. Furthermore, the DHC exhibited hepatocyte-specific functions, including albumin secretion, low-density lipoprotein uptake and urea production. More importantly, DHC did not express major histocompatibility complex (MHC) II antigen and were not able to induce lymphocyte proliferation in mixed lymphocyte culture, as undifferentiated UC MSC did. Our results indicate that UC MSC are able to differentiate into functional hepatocyte-like cells that still retain their low immunogenicity in vitro. More importantly, DHC incorporated into the parenchyma of liver when transplanted into mice with CCl(4)-induced liver injury. Therefore, DHC may be an ideal source for cell therapy of liver diseases.
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A Reproducible Immunopotency Assay to Measure Mesenchymal Stromal Cell Mediated T cell Suppression
Bloom, Debra D.; Centanni, John M.; Bhatia, Neehar; Emler, Carol A.; Drier, Diana; Leverson, Glen E.; McKenna, David H.; Gee, Adrian P.; Lindblad, Robert; Hei, Derek J.; Hematti, Peiman
2014-01-01
Background The T cell suppressive property of bone marrow derived mesenchymal stromal cells (MSCs) has been considered a major mode of action and basis for their utilization in a number of human clinical trials. However, there is no well-established reproducible assay to measure MSC-mediated T cell suppression. Methods At the University of Wisconsin-Madison Production Assistance for Cellular Therapy (PACT) Center we developed an in vitro quality control T cell suppression immunopotency assay (IPA) which utilizes anti-CD3 and anti-CD28 antibodies to stimulate T cell proliferation. We measured MSC-induced suppression of CD4+ T cell proliferation at various effector to target cell ratios using defined peripheral blood mononuclear cells and in parallel compared to a reference standard MSC product. We calculated an IPA value for suppression of CD4+ T cells for each MSC product. Results Eleven MSC products generated at three independent PACT centers were evaluated for cell surface phenotypic markers and T cell suppressive properties. Flow cytometry results demonstrated typical MSC cell surface marker profiles. There was significant variability in the level of suppression of T cell proliferation with IPA values ranging from 27% to 88%. However, MSC suppression did not correlate with HLA-DR expression. Discussion We have developed a reproducible immunopotency assay to measure allogeneic MSC-mediated suppression of CD4+ T cells. Additional studies may be warranted to determine how these in vitro assay results may correlate with other immunomodulatory properties of MSCs, in addition to evaluating the ability of this assay to predict in vivo efficacy. PMID:25455739
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Kwon, Tae-Rin; Oh, Chang Taek; Choi, Eun Ja; Kim, Soon Re; Jang, Yu-Jin; Ko, Eun Jung; Yoo, Kwang Ho; Kim, Beom Joon
2016-05-01
Mesenchymal stem cells (MSCs) are promising therapeutic agents for various diseases. To investigate the effects of conditioned medium from human bone marrow-derived mesenchymal stem cells (MSC-CdM) on pro-collagen production and wrinkle formation, we performed in vitro and in vivo experiments. We assessed the effects of MSC-CdM on proliferation and photo-aging in human dermal fibroblasts after UVB exposure using enzyme activity assays for collagen type I secretion and MMP-1. To determine the effect of topically applied MSC-CdM on wrinkle formation, MSC-CdM (1% and 10%) and vehicle (propylene glycol: ethanol, 7 : 3) were applied to the dorsal skin of UVB-irradiated hairless mice for 8 weeks. We examined the effects on wrinkle formation by assessing visual skin grading, replica, tape stripping, transepidermal water loss (TEWL), and skin hydration measurement. We also examined histology of the lesions using hematoxylin-eosin, Masson's trichrome, and immunohistochemical staining. MSC-CdM markedly reduced UV-induced matrix metalloproteinase-1 expression and increased pro-collagen synthesis in a dose-dependent manner. Our findings suggest that MSC-CdM induces repair of dermal damage and effacement of wrinkles on UVB-irradiated hairless mice through protective effect of hydration. These results support an anti-wrinkle effect of MSC-CdM that involves increased collagen synthesis and suggest that MSC-CdM might be a potential candidate for preventing UV-induced skin damage. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
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NASA Astrophysics Data System (ADS)
Gouveia, Diego; Baars, Holger; Seifert, Patric; Wandinger, Ulla; Barbosa, Henrique; Barja, Boris; Artaxo, Paulo; Lopes, Fabio; Landulfo, Eduardo; Ansmann, Albert
2018-04-01
Lidar measurements of cirrus clouds are highly influenced by multiple scattering (MS). We therefore developed an iterative approach to correct elastic backscatter lidar signals for multiple scattering to obtain best estimates of single-scattering cloud optical depth and lidar ratio as well as of the ice crystal effective radius. The approach is based on the exploration of the effect of MS on the molecular backscatter signal returned from above cloud top.
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Aleksejevs, Aleksandrs; Barkanova, Svetlana; Ilyichev, Alexander; ...
2010-11-19
We perform updated and detailed calculations of the complete NLO set of electroweak radiative corrections to parity violating e – e – → e – e – (γ) scattering asymmetries at energies relevant for the ultra-precise Moller experiment coming soon at JLab. Our numerical results are presented for a range of experimental cuts and relative importance of various contributions is analyzed. In addition, we also provide very compact expressions analytically free from non-physical parameters and show them to be valid for fast yet accurate estimations.
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Hadron mass corrections in semi-inclusive deep-inelastic scattering
Guerrero Teran, Juan Vicente; Ethier, James J.; Accardi, Alberto; ...
2015-09-24
We found that the spin-dependent cross sections for semi-inclusive lepton-nucleon scattering are derived in the framework of collinear factorization, including the effects of masses of the target and produced hadron at finite Q 2. At leading order the cross sections factorize into products of parton distribution and fragmentation functions evaluated in terms of new, mass-dependent scaling variables. Furthermore, the size of the hadron mass corrections is estimated at kinematics relevant for current and future experiments, and the implications for the extraction of parton distributions from semi-inclusive measurements are discussed.
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a Phenomenological Determination of the Pion-Nucleon Scattering Lengths from Pionic Hydrogen
NASA Astrophysics Data System (ADS)
Ericson, T. E. O.; Loiseau, B.; Wycech, S.
A model independent expression for the electromagnetic corrections to a phenomenological hadronic pion-nucleon (πN) scattering length ah, extracted from pionic hydrogen, is obtained. In a non-relativistic approach and using an extended charge distribution, these corrections are derived up to terms of order α2 log α in the limit of a short-range hadronic interaction. We infer ahπ ^-p=0.0870(5)m-1π which gives for the πNN coupling through the GMO relation g2π ^± pn/(4π )=14.04(17).
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Induced Pluripotent Stem Cell Derived Mesenchymal Stem Cells for Attenuating Age-Related Bone Loss
2012-07-01
Mesenchymal stem cell (MSC) differentiation towards the bone forming osteoblastic lineage decreases as a function of age and may contribute to age-related...problem of age-related reduced availability of MSC we propose to examine the bone anabolic potential of induced pluripotent stem cell (iPS) derived MSC
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Dr. Gilruth and Dr. Kraft - Mission Control Center (MCC) - Apollo V Launch - MSC
1968-01-22
S68-18733 (22 Jan. 1968) --- Dr. Robert R. Gilruth (right), MSC Director, sits with Dr. Christopher C. Kraft Jr., MSC director of flight operations, at his flight operations director console in the Mission Control Center, Building 30, during the Apollo 5 (LM-1/Saturn 204) unmanned space mission.
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76 FR 35480 - Notice of Intent To Grant Partially Exclusive License
Federal Register 2010, 2011, 2012, 2013, 2014
2011-06-17
..., Endothelium Preserving Microwave Treatment For Atherosclerosis, NASA Case No. MSC- 22724-1, USPN 6,226,553, Endothelium Preserving Microwave Treatment For Atherosclerosis, NASA Case No. MSC-22724-2, USPN 6,223,086, Endothelium Preserving Microwave Treatment For Atherosclerosis, NASA Case No. MSC- 22724-3, and USPN 6,496,736...
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Ding, Wei; Nowakowski, Grzegorz S; Knox, Traci R; Boysen, Justin C; Maas, Mary L; Schwager, Susan M; Wu, Wenting; Wellik, Linda E; Dietz, Allan B; Ghosh, Asish K; Secreto, Charla R; Medina, Kay L; Shanafelt, Tait D; Zent, Clive S; Call, Timothy G; Kay, Neil E
2009-11-01
It was hypothesized that contact between chronic lymphocytic leukaemia (CLL) B-cells and marrow stromal cells impact both cell types. To test this hypothesis, we utilized a long-term primary culture system from bone biopsies that reliably generates a mesenchymal stem cell (MSC). Co-culture of MSC with CLL B-cells protected the latter from both spontaneous apoptosis and drug-induced apoptosis. The CD38 expression in previously CD38 positive CLL B-cells was up-regulated with MSC co-culture. Upregulation of CD71, CD25, CD69 and CD70 in CLL B-cells was found in the co-culture. CD71 upregulation was more significantly associated with high-risk CLL, implicating CD71 regulation in the microenvironment predicting disease progression. In MSC, rapid ERK and AKT phosphorylation (within 30 min) were detected when CLL B-cells and MSC were separated by transwell; indicating that activation of MSC was mediated by soluble factors. These findings support a bi-directional activation between bone marrow stromal cells and CLL B-cells.
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Rodrigo, Sander F; van Ramshorst, Jan; Hoogslag, Georgette E; Boden, Helèn; Velders, Matthijs A; Cannegieter, Suzanne C; Roelofs, Helene; Al Younis, Imad; Dibbets-Schneider, Petra; Fibbe, Willem E; Zwaginga, Jaap Jan; Bax, Jeroen J; Schalij, Martin J; Beeres, Saskia L; Atsma, Douwe E
2013-10-01
In experimental studies, mesenchymal stem cell (MSC) transplantation in acute myocardial infarction (AMI) models has been associated with enhanced neovascularization and myogenesis. Clinical data however, are scarce. Therefore, the present study evaluates the safety and feasibility of intramyocardial MSC injection in nine patients, shortly after AMI during short-term and 5-year follow-up. Periprocedural safety analysis demonstrated one transient ischemic attack. No other adverse events related to MSC treatment were observed during 5-year follow-up. Clinical events were compared to a nonrandomized control group comprising 45 matched controls. A 5-year event-free survival after MSC-treatment was comparable to controls (89 vs. 91 %, P = 0.87). Echocardiographic imaging for evaluation of left ventricular function demonstrated improvements up to 5 years after MSC treatment. These findings were not significantly different when compared to controls. The present safety and feasibility study suggest that intramyocardial injection of MSC in patients shortly after AMI is feasible and safe up to 5-year follow-up.
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Adaptation of MSC/NASTRAN to a supercomputer
DOE Office of Scientific and Technical Information (OSTI.GOV)
Gloudeman, J.F.; Hodge, J.C.
1982-01-01
MSC/NASTRAN is a large-scale general purpose digital computer program which solves a wider variety of engineering analysis problems by the finite element method. The program capabilities include static and dynamic structural analysis (linear and nonlinear), heat transfer, acoustics, electromagnetism and other types of field problems. It is used worldwide by large and small companies in such diverse fields as automotive, aerospace, civil engineering, shipbuilding, offshore oil, industrial equipment, chemical engineering, biomedical research, optics and government research. The paper presents the significant aspects of the adaptation of MSC/NASTRAN to the Cray-1. First, the general architecture and predominant functional use of MSC/NASTRANmore » are discussed to help explain the imperatives and the challenges of this undertaking. The key characteristics of the Cray-1 which influenced the decision to undertake this effort are then reviewed to help identify performance targets. An overview of the MSC/NASTRAN adaptation effort is then given to help define the scope of the project. Finally, some measures of MSC/NASTRAN's operational performance on the Cray-1 are given, along with a few guidelines to help avoid improper interpretation. 17 references.« less
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Influence of long-term gravity vector changes on mesenchymal stem cells in vitro
NASA Astrophysics Data System (ADS)
Buravkova, L. B.; Merzlikina, N. V.; Romanov, Yu. A.; Buravkov, S. V.
2005-08-01
In vivo and in vitro studies have identified the bone marrow as the primary source of a multipotential mesenchymal stem cells (MSC) that give rise to progenitors for several mesenchymal tissues, including bone, cartilage, tendon, adipose, muscle and hematopoietic-supporting stroma. It is known that MSC are sensitive to chemical signals and mechanical stimuli. It was also suggested that microgravity may influence on progenitor cells and induce abnormalities in cellular differentiation in muscle and skeletal components leading to the changes in physiological regeneration of these tissues. To prove gravitational sensitivity of MSC, we studied the effects of prolonged clinorotation on cultured human MSC (hMSC) morphology, actin cytoskeleton organization and phenotype. It was found that the proliferation rate was significantly decreased during clinorotation but augmented during recovery. The cell cytoskeleton displayed actin filament thinning and altered morphology at clinorotation. The production of interleukin-6 was increased and expression of surface molecules was modified by simulated microgravity. Observed changes of cultured hMSC behavior suggest the gravitational sensitivity of human stromal progenitor cells.
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Weaver, Aaron S; Su, Yu-Ping; Begun, Dana L; Miller, Joshua D; Alford, Andrea I; Goldstein, Steven A
2010-07-01
The local mechanical environment and the availability of mesenchymal stem cells (MSC) have both been shown to be important factors in bone fracture healing. This study was designed to investigate how the timing of an applied axial displacement across a healing fracture affects callus properties as well as the migration of systemically introduced MSC. Bilateral osteotomies were created in male, Sprague-Dawley rats. Exogenous MSC were injected via the tail vein, and a controlled micro-motion was applied to one defect starting 0, 3, 10, or 24 days after surgery. The results showed that fractures stimulated 10 days after surgery had more mineral, less cartilage, and greater mechanical properties at 48 days than other groups. Populations of MSC were found in osteotomies 48 days after surgery, with the exception of the group that was stimulated 10 days after surgery. These results demonstrate that the timing of mechanical stimulation affects the physical properties of the callus and the migration of MSC to the fracture site. Published by Elsevier Inc.
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N3LO corrections to jet production in deep inelastic scattering using the Projection-to-Born method
NASA Astrophysics Data System (ADS)
Currie, J.; Gehrmann, T.; Glover, E. W. N.; Huss, A.; Niehues, J.; Vogt, A.
2018-05-01
Computations of higher-order QCD corrections for processes with exclusive final states require a subtraction method for real-radiation contributions. We present the first-ever generalisation of a subtraction method for third-order (N3LO) QCD corrections. The Projection-to-Born method is used to combine inclusive N3LO coefficient functions with an exclusive second-order (NNLO) calculation for a final state with an extra jet. The input requirements, advantages, and potential applications of the method are discussed, and validations at lower orders are performed. As a test case, we compute the N3LO corrections to kinematical distributions and production rates for single-jet production in deep inelastic scattering in the laboratory frame, and compare them with data from the ZEUS experiment at HERA. The corrections are small in the central rapidity region, where they stabilize the predictions to sub per-cent level. The corrections increase substantially towards forward rapidity where large logarithmic effects are expected, thereby yielding an improved description of the data in this region.
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GEO-LEO reflectance band inter-comparison with BRDF and atmospheric scattering corrections
NASA Astrophysics Data System (ADS)
Chang, Tiejun; Xiong, Xiaoxiong Jack; Keller, Graziela; Wu, Xiangqian
2017-09-01
The inter-comparison of the reflective solar bands between the instruments onboard a geostationary orbit satellite and onboard a low Earth orbit satellite is very helpful to assess their calibration consistency. GOES-R was launched on November 19, 2016 and Himawari 8 was launched October 7, 2014. Unlike the previous GOES instruments, the Advanced Baseline Imager on GOES-16 (GOES-R became GOES-16 after November 29 when it reached orbit) and the Advanced Himawari Imager (AHI) on Himawari 8 have onboard calibrators for the reflective solar bands. The assessment of calibration is important for their product quality enhancement. MODIS and VIIRS, with their stringent calibration requirements and excellent on-orbit calibration performance, provide good references. The simultaneous nadir overpass (SNO) and ray-matching are widely used inter-comparison methods for reflective solar bands. In this work, the inter-comparisons are performed over a pseudo-invariant target. The use of stable and uniform calibration sites provides comparison with appropriate reflectance level, accurate adjustment for band spectral coverage difference, reduction of impact from pixel mismatching, and consistency of BRDF and atmospheric correction. The site in this work is a desert site in Australia (latitude -29.0 South; longitude 139.8 East). Due to the difference in solar and view angles, two corrections are applied to have comparable measurements. The first is the atmospheric scattering correction. The satellite sensor measurements are top of atmosphere reflectance. The scattering, especially Rayleigh scattering, should be removed allowing the ground reflectance to be derived. Secondly, the angle differences magnify the BRDF effect. The ground reflectance should be corrected to have comparable measurements. The atmospheric correction is performed using a vector version of the Second Simulation of a Satellite Signal in the Solar Spectrum modeling and BRDF correction is performed using a semi-empirical model. AHI band 1 (0.47μm) shows good matching with VIIRS band M3 with difference of 0.15%. AHI band 5 (1.69μm) shows largest difference in comparison with VIIRS M10.
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Scientific data reduction and analysis plan: PI services
NASA Technical Reports Server (NTRS)
Feldman, P. D.; Fastie, W. G.
1971-01-01
This plan comprises two parts. The first concerns the real-time data display to be provided by MSC during the mission. The prime goal is to assess the operation of the UVS and to identify any problem areas that could be corrected during the mission. It is desirable to identify any possible observations of unusual scientific interest in order to repeat these observations at a later point in the mission, or to modify the time line with respect to the operating modes of the UVS. The second part of the plan discusses the more extensive postflight analysis of the data in terms of the scientific objectives of this experiment.
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Development of PET projection data correction algorithm
NASA Astrophysics Data System (ADS)
Bazhanov, P. V.; Kotina, E. D.
2017-12-01
Positron emission tomography is modern nuclear medicine method used in metabolism and internals functions examinations. This method allows to diagnosticate treatments on their early stages. Mathematical algorithms are widely used not only for images reconstruction but also for PET data correction. In this paper random coincidences and scatter correction algorithms implementation are considered, as well as algorithm of PET projection data acquisition modeling for corrections verification.
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Choi, Seung Ah; Yun, Jun-Won; Joo, Kyeung Min; Lee, Ji Yeoun; Kwak, Pil Ae; Lee, Young Eun; You, Ji-Ran; Kwon, Euna; Kim, Woo Ho; Wang, Kyu-Chang; Phi, Ji Hoon; Kang, Byeong-Cheol; Kim, Seung-Ki
2016-06-15
Stem-cell based gene therapy is a promising novel therapeutic approach for inoperable invasive tumors, including brainstem glioma. Previously, we demonstrated the therapeutic potential of human adipose tissue-derived mesenchymal stem cells (hAT-MSC) genetically engineered to express a secreted form of tumor necrosis factor-related apoptosis-inducing ligand (sTRAIL) against brainstem glioma. However, safety concerns should be comprehensively investigated before clinical applications of hAT-MSC.sTRAIL. At first, we injected stereotactically low (1.2 × 10(5) cells/18 μL), medium (2.4 × 10(5)/18 μL), or high dose (3.6 × 10(5)/18 μL) of hAT-MSC.sTRAIL into the brainstems of immunodeficient mice reflecting the plan of the future clinical trial. Local toxicity, systemic toxicity, secondary tumor formation, and biodistribution of hAT-MSC.sTRAIL were investigated. Next, presence of hAT-MSC.sTRAIL was confirmed in the brain and major organs at 4, 9, and 14 weeks in brainstem glioma-bearing mice. In the 15-week subchronic toxicity test, no serious adverse events in terms of body weight, food consumption, clinical symptom, urinalysis, hematology, clinical chemistry, organ weight, and histopathology were observed. In the 26-week tumorigenicity test, hAT-MSC.sTRAIL made no detectable tumors, whereas positive control U-87 MG cells made huge tumors in the brainstem. No remaining hAT-MSC.sTRAIL was observed in any organs examined, including the brainstem at 15 or 26 weeks. In brainstem glioma-bearing mice, injected hAT-MSC.sTRAIL was observed, but gradually decreased over time in the brain. The mRNA of human specific GAPDH and TRAIL was not detected in all major organs. These results indicate that the hAT-MSC.sTRAIL could be applicable to the future clinical trials in terms of biosafety.
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Donega, Vanessa; Nijboer, Cora H; van Tilborg, Geralda; Dijkhuizen, Rick M; Kavelaars, Annemieke; Heijnen, Cobi J
2014-11-01
Previous work from our group has shown that intranasal MSC-treatment decreases lesion volume and improves motor and cognitive behavior after hypoxic-ischemic (HI) brain damage in neonatal mice. Our aim was to determine the kinetics of MSC migration after intranasal administration, and the early effects of MSCs on neurogenic processes and gliosis at the lesion site. HI brain injury was induced in 9-day-old mice and MSCs were administered intranasally at 10days post-HI. The kinetics of MSC migration were investigated by immunofluorescence and MRI analysis. BDNF and NGF gene expression was determined by qPCR analysis following MSC co-culture with HI brain extract. Nestin, Doublecortin, NeuN, GFAP, Iba-1 and M1/M2 phenotypic expression was assessed over time. MRI and immunohistochemistry analyses showed that MSCs reach the lesion site already within 2h after intranasal administration. At 12h after administration the number of MSCs at the lesion site peaks and decreases significantly at 72h. The number of DCX(+) cells increased 1 to 3days after MSC administration in the SVZ. At the lesion, GFAP(+)/nestin(+) and DCX(+) expression increased 3 to 5days after MSC-treatment. The number of NeuN(+) cells increased within 5days, leading to a dramatic regeneration of the somatosensory cortex and hippocampus at 18days after intranasal MSC administration. Interestingly, MSCs expressed significantly more BDNF gene when exposed to HI brain extract in vitro. Furthermore, MSC-treatment resulted in the resolution of the glial scar surrounding the lesion, represented by a decrease in reactive astrocytes and microglia and polarization of microglia towards the M2 phenotype. In view of the current lack of therapeutic strategies, we propose that intranasal MSC administration is a powerful therapeutic option through its functional repair of the lesion represented by regeneration of the cortical and hippocampal structure and decrease of gliosis. Copyright © 2014. Published by Elsevier Inc.
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Wu, Yi-Hsuan; Taggart, Janet; Song, Pamela Xiyao; MacDiarmid, Colin; Eide, David J.
2016-01-01
The Msc2 and Zrg17 proteins of Saccharomyces cerevisiae form a complex to transport zinc into the endoplasmic reticulum. ZRG17 is transcriptionally induced in zinc-limited cells by the Zap1 transcription factor. In this report, we show that MSC2 mRNA also increases (~1.5 fold) in zinc-limited cells. The MSC2 gene has two in-frame ATG codons at its 5’ end, ATG1 and ATG2; ATG2 is the predicted initiation codon. When the MSC2 promoter was fused at ATG2 to the lacZ gene, we found that unlike the chromosomal gene this reporter showed a 4-fold decrease in lacZ mRNA in zinc-limited cells. Surprisingly, β-galactosidase activity generated by this fusion gene increased ~7 fold during zinc deficiency suggesting the influence of post-transcriptional factors. Transcription of MSC2ATG2-lacZ was found to start upstream of ATG1 in zinc-replete cells. In zinc-limited cells, transcription initiation shifted to sites just upstream of ATG2. From the results of mutational and polysome profile analyses, we propose the following explanation for these effects. In zinc-replete cells, MSC2ATG2-lacZ mRNA with long 5’ UTRs fold into secondary structures that inhibit translation. In zinc-limited cells, transcripts with shorter unstructured 5’ UTRs are generated that are more efficiently translated. Surprisingly, chromosomal MSC2 did not show start site shifts in response to zinc status and only shorter 5’ UTRs were observed. However, the shifts that occur in the MSC2ATG2-lacZ construct led us to identify significant transcription start site changes affecting the expression of ~3% of all genes. Therefore, zinc status can profoundly alter transcription initiation across the yeast genome. PMID:27657924
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Role of SDF‐1:CXCR4 in Impaired Post‐Myocardial Infarction Cardiac Repair in Diabetes
Mayorga, Maritza E.; Kiedrowski, Matthew; McCallinhart, Patricia; Forudi, Farhad; Ockunzzi, Jeremiah; Weber, Kristal; Chilian, William; Penn, Marc S.
2017-01-01
Abstract Diabetes is a risk factor for worse outcomes following acute myocardial infarction (AMI). In this study, we tested the hypothesis that SDF‐1:CXCR4 expression is compromised in post‐AMI in diabetes, and that reversal of this defect can reverse the adverse effects of diabetes. Mesenchymal stem cells (MSC) isolated from green fluorescent protein (GFP) transgenic mice (control MSC) were induced to overexpress stromal cell‐derived factor‐1 (SDF‐1). SDF‐1 expression in control MSC and SDF‐1‐overexpressing MSC (SDF‐1:MSC) were quantified using enzyme‐linked immunosorbent assay (ELISA). AMI was induced on db/db and control mice. Mice were randomly selected to receive infusion of control MSC, SDF‐1:MSC, or saline into the border zone after AMI. Serial echocardiography was used to assess cardiac function. SDF‐1 and CXCR4 mRNA expression in the infarct zone of db/db mice and control mice were quantified. Compared to control mice, SDF‐1 levels were decreased 82%, 91%, and 45% at baseline, 1 day and 3 days post‐AMI in db/db mice, respectively. CXCR4 levels are increased 233% at baseline and 54% 5 days post‐AMI in db/db mice. Administration of control MSC led to a significant improvement in ejection fraction (EF) in control mice but not in db/db mice 21 days after AMI. In contrast, administration of SDF‐1:MSC produced a significant improvement in EF in both control mice and db/db mice 21 days after AMI. The SDF‐1:CXCR4 axis is compromised in diabetes, which appears to augment the deleterious consequences of AMI. Over‐express of SDF‐1 expression in diabetes rescues cardiac function post AMI. Our results suggest that modulation of SDF‐1 may improve post‐AMI cardiac repair in diabetes. stem cells translational medicine 2018;7:115–124 PMID:29119710
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Biologic injections for osteoarthritis and articular cartilage damage: can we modify disease?
Shi, Weilong J; Tjoumakaris, Fotios P; Lendner, Mayan; Freedman, Kevin B
2017-09-01
The purpose of the present investigation is to conduct a systematic review of the literature to review the clinical results of platelet rich plasma (PRP) and mesenchymal stem cell treatments (MSC) (biologics) for articular cartilage lesions and osteoarthritis of the knee. A search of the PubMed, EMBASE, and Cochrane databases was performed to identify studies involving biologic therapy for osteoarthritis or osteochondral defects. Only Level I-III clinical trials with at least 3-month follow-up were included. Outcome data was gathered on any patient-completed surveys, 2nd look arthroscopy, follow-up imaging, biopsy/histology results, and any adverse effects of treatment. Thirty-three articles met our inclusion criteria. There was a total of 21 PRP studies in the study. All PRP studies showed clinical improvement with PRP therapies in outcomes surveys measuring patient satisfaction, pain, and function. Two studies reported no significant difference in improvement compared to hyaluronic acid (HA). Similarly, the 7/9 MSC studies showed improvement. One study found BM-MSC implantation was not significantly superior to matrix assisted chondrocyte implantation (MACI), while one reported peripheral blood stem cells (PBSC) did not significantly improve outcomes over HA. Of the three studies looking at a combination of MSC/PRP, two found MSC/PRP combination did not improve outcomes compared to MSC or PRP therapy alone. The one PRP study that had a 2nd look arthroscopy reported increases cartilage regeneration with PRP. All 8 MSC studies with follow-up MRI and all 7 MSC studies with 2nd look arthroscopy showed improvement in cartilage regeneration in terms of coverage, fill of the defect, and/or firmness of the new cartilage. Current data suggests that, of the two treatments, MSC provides more significant disease modifying effect; however, further research needs to be done to compare these two treatments and determine if there is a synergetic effect when combined.
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Correction of WindScat Scatterometric Measurements by Combining with AMSR Radiometric Data
NASA Technical Reports Server (NTRS)
Song, S.; Moore, R. K.
1996-01-01
The Seawinds scatterometer on the advanced Earth observing satellite-2 (ADEOS-2) will determine surface wind vectors by measuring the radar cross section. Multiple measurements will be made at different points in a wind-vector cell. When dense clouds and rain are present, the signal will be attenuated, thereby giving erroneous results for the wind. This report describes algorithms to use with the advanced mechanically scanned radiometer (AMSR) scanning radiometer on ADEOS-2 to correct for the attenuation. One can determine attenuation from a radiometer measurement based on the excess brightness temperature measured. This is the difference between the total measured brightness temperature and the contribution from surface emission. A major problem that the algorithm must address is determining the surface contribution. Two basic approaches were developed for this, one using the scattering coefficient measured along with the brightness temperature, and the other using the brightness temperature alone. For both methods, best results will occur if the wind from the preceding wind-vector cell can be used as an input to the algorithm. In the method based on the scattering coefficient, we need the wind direction from the preceding cell. In the method using brightness temperature alone, we need the wind speed from the preceding cell. If neither is available, the algorithm can work, but the corrections will be less accurate. Both correction methods require iterative solutions. Simulations show that the algorithms make significant improvements in the measured scattering coefficient and thus is the retrieved wind vector. For stratiform rains, the errors without correction can be quite large, so the correction makes a major improvement. For systems of separated convective cells, the initial error is smaller and the correction, although about the same percentage, has a smaller effect.
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Mesenchymal Stem Cells Stabilize Atherosclerotic Vulnerable Plaque by Anti-Inflammatory Properties
Wang, Shuang-shuang; Hu, Si-wang; Zhang, Qing-hua; Xia, Ai-xiang
2015-01-01
Background and objectives Formation and progression of atherosclerotic vulnerable plaque (VP) is the primary cause of many cardio-cerebrovascular diseases such as acute coronary syndrome and stroke. It has been reported that bone marrow mesenchymal stem cells (MSC) exhibit protective effects against many kinds of diseases including myocardial infarction. Here, we examined the effects of intravenous MSC infusion on a VP model and provide novel evidence of its influence as a therapy in this animal disease model. Subjects and methods Thirty healthy male New Zealand white rabbits were randomly divided into a MSC, VP or stable plaque (SP) group (n = 10/group) and received high fat diet and cold-induced common carotid artery intimal injury with liquid nitrogen to form atherosclerotic plaques. Serum hs-CRP, TNF-α, IL-6 and IL-10 levels were measured by ELISA at 1, 2, 3, 7, 14, 21 and 28 days after MSC transplantation. The animals were sacrificed at 4 weeks after MSC transplantation. Lesions in the right common carotid were observed using H&E and Masson staining, and the fibrous cap/lipid core ratio of atherosclerotic plaques were calculated. The expression of nuclear factor κB (NF-κB) and matrix metalloproteinase 1, 2, 9 (MMP-1,2,9) in the plaque were detected using immunohistochemistry, and apoptotic cells in the plaques were detected by TUNEL. In addition, the level of TNF-α stimulated gene/protein 6 (TSG-6) mRNA and protein were measured by quantitative Real-Time PCR and Western blotting, respectively. Results Two rabbits in the VP group died of lung infection and cerebral infarction respectively at 1 week after plaque injury by liquid nitrogen. Both H&E and Masson staining revealed that the plaques from the SP and MSC groups had more stable morphological structure and a larger fibrous cap/lipid core ratio than the VP group. Serum hs-CRP, TNF-α and IL-6 were significantly down-regulated, whereas IL-10 was significantly up-regulated in the MSC group compared with the VP group. .Immunohistochemistry analysis revealed that NF-κB and MMP expression was reduced in the MSC and SP groups compared to the VP group. Cell apoptosis decreased significantly in both the MSC and SP groups in comparison to the VP group. TSG-6 mRNA and protein expression were higher in the plaques of the MSC group compared to the VP and SP groups. Conclusions Our study results suggest that MSC transplantation can effectively stabilize vulnerable plaques in atherosclerotic rabbits. This may potentially offer a new clinical application of MSC in atherosclerosis. PMID:26288013
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Kim, J; Park, Y; Sharp, G
Purpose: To establish a method to evaluate the dosimetric impact of anatomic changes in head and neck patients during proton therapy by using scatter-corrected cone-beam CT (CBCT) images. Methods: The water equivalent path length (WEPL) was calculated to the distal edge of PTV contours by using tomographic images available for six head and neck patients received photon therapy. The proton range variation was measured by calculating the difference between the distal WEPLs calculated with the planning CT and weekly treatment CBCT images. By performing an automatic rigid registration, six degrees-of-freedom (DOF) correction was made to the CBCT images to accountmore » for the patient setup uncertainty. For accurate WEPL calculations, an existing CBCT scatter correction algorithm, whose performance was already proven for phantom images, was calibrated for head and neck patient images. Specifically, two different image similarity measures, mutual information (MI) and mean square error (MSE), were tested for the deformable image registration (DIR) in the CBCT scatter correction algorithm. Results: The impact of weight loss was reflected in the distal WEPL differences with the aid of the automatic rigid registration reducing the influence of patient setup uncertainty on the WEPL calculation results. The WEPL difference averaged over distal area was 2.9 ± 2.9 (mm) across all fractions of six patients and its maximum, mostly found at the last available fraction, was 6.2 ± 3.4 (mm). The MSE-based DIR successfully registered each treatment CBCT image to the planning CT image. On the other hand, the MI-based DIR deformed the skin voxels in the planning CT image to the immobilization mask in the treatment CBCT image, most of which was cropped out of the planning CT image. Conclusion: The dosimetric impact of anatomic changes was evaluated by calculating the distal WEPL difference with the existing scatter-correction algorithm appropriately calibrated. Jihun Kim, Yang-Kyun Park, Gregory Sharp, and Brian Winey have received grant support from the NCI Federal Share of program income earned by Massachusetts General Hospital on C06 CA059267, Proton Therapy Research and Treatment Center.« less
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Shi, Ming; Zhang, Zheng; Xu, Ruonan; Lin, Hu; Fu, Junliang; Zou, Zhengsheng; Zhang, Aimin; Shi, Jianfei; Chen, Liming; Lv, Sa; He, Weiping; Geng, Hua; Jin, Lei; Liu, Zhenwen
2012-01-01
Acute-on-chronic liver failure (ACLF) is a severe, life-threatening complication, and new and efficient therapeutic strategies for liver failure are urgently needed. Mesenchymal stem cell (MSC) transfusions have been shown to reverse fulminant hepatic failure in mice and to improve liver function in patients with end-stage liver diseases. We assessed the safety and initial efficacy of umbilical cord-derived MSC (UC-MSC) transfusions for ACLF patients associated with hepatitis B virus (HBV) infection. A total of 43 ACLF patients were enrolled for this open-labeled and controlled study; 24 patients were treated with UC-MSCs, and 19 patients were treated with saline as controls. UC-MSC therapy was given three times at 4-week intervals. The liver function, adverse events, and survival rates were evaluated during the 48-week or 72-week follow-up period. No significant side effects were observed during the trial. The UC-MSC transfusions significantly increased the survival rates in ACLF patients; reduced the model for end-stage liver disease scores; increased serum albumin, cholinesterase, and prothrombin activity; and increased platelet counts. Serum total bilirubin and alanine aminotransferase levels were significantly decreased after the UC-MSC transfusions. UC-MSC transfusions are safe in the clinic and may serve as a novel therapeutic approach for HBV-associated ACLF patients. PMID:23197664
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Yuniartha, Ratih; Alatas, Fatima Safira; Nagata, Kouji; Kuda, Masaaki; Yanagi, Yusuke; Esumi, Genshiro; Yamaza, Takayoshi; Kinoshita, Yoshiaki; Taguchi, Tomoaki
2014-09-01
The aim of this study was to evaluate the efficacy of mesenchymal stem cells (MSCs) in a nitrofen-induced congenital diaphragmatic hernia (CDH) rat model. Pregnant rats were exposed to nitrofen on embryonic day 9.5 (E9.5). MSCs were isolated from the enhanced green fluorescent protein (eGFP) transgenic rat lungs. The MSCs were transplanted into the nitrofen-induced E12.5 rats via the uterine vein, and the E21 lung explants were harvested. The study animals were divided into three: the control group, the nitrofen-induced left CDH (CDH group), and the MSC-treated nitrofen-induced left CDH (MSC-treated CDH group). The specimens were morphologically analyzed using HE and immunohistochemical staining with proliferating cell nuclear antigen (PCNA), surfactant protein-C (SP-C), and α-smooth muscle actin. The alveolar and medial walls of the pulmonary arteries were significantly thinner in the MSC-treated CDH group than in the CDH group. The alveolar air space areas were larger, while PCNA and the SP-C positive cells were significantly higher in the MSC-treated CDH group, than in the CDH group. MSC engraftment was identified on immunohistochemical staining of the GFP in the MSC-treated CDH group. MSC transplantation potentially promotes alveolar and pulmonary artery development, thereby reducing the severity of pulmonary hypoplasia.
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Kumagai, Gentaro; Tsoulfas, Pantelis; Toh, Satoshi; McNiece, Ian; Bramlett, Helen M; Dietrich, W Dalton
2013-10-01
Neurotrophins and the transplantation of bone marrow-derived stromal cells (MSCs) are both candidate therapies targeting spinal cord injury (SCI). While some studies have suggested the ability of MSCs to transdifferentiate into neural cells, other SCI studies have proposed anti-inflammatory and other mechanisms underlying established beneficial effects. We grafted rat MSCs genetically modified to express MNTS1, a multineurotrophin that binds TrkA, TrkB and TrkC, and p75(NTR) receptors or MSC-MNTS1/p75(-) that binds mainly to the Trk receptors. Seven days after contusive SCI, PBS-only, GFP-MSC, MSC-MNTS1/GFP or MSC-MNTS1/p75(-)/GFP were delivered into the injury epicenter. All transplanted groups showed reduced inflammation and cystic cavity size compared to control SCI rats. Interestingly, transplantation of the MSC-MNTS1 and MSC-MNTS1/p75(-), but not the naïve MSCs, enhanced axonal growth and significantly prevented cutaneous hypersensitivity after SCI. Moreover, transplantation of MSC-MNTS1/p75(-) promoted angiogenesis and modified glial scar formation. These findings suggest that MSCs transduced with a multineurotrophin are effective in promoting cell growth and improving sensory function after SCI. These novel data also provide insight into the neurotrophin-receptor dependent mechanisms through which cellular transplantation leads to functional improvement after experimental SCI. © 2013.
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Additive effect of mesenchymal stem cells and defibrotide in an arterial rat thrombosis model.
Dilli, Dilek; Kılıç, Emine; Yumuşak, Nihat; Beken, Serdar; Uçkan Çetinkaya, Duygu; Karabulut, Ramazan; Zenciroğlu, Ayşegu L
2017-06-01
In this study, we aimed to investigate the additive effect of mesenchymal stem cells (MSC) and defibrotide (DFT) in a rat model of femoral arterial thrombosis. Thirty Sprague Dawley rats were included. An arterial thrombosis model by ferric chloride (FeCl3) was developed in the left femoral artery. The rats were equally assigned to 5 groups: Group 1-Sham-operated (without arterial injury); Group 2-Phosphate buffered saline (PBS) injected; Group 3-MSC; Group 4-DFT; Group 5-MSC + DFT. All had two intraperitoneal injections of 0.5 ml: the 1st injection was 4 h after the procedure and the 2nd one 48 h after the 1st injection. The rats were sacrificed 7 days after the 2nd injection. Although the use of human bone marrow-derived (hBM) hBM-MSC or DFT alone enabled partial resolution of the thrombus, combining them resulted in near-complete resolution. Neovascularization was two-fold better in hBM-MSC + DFT treated rats (11.6 ± 2.4 channels) compared with the hBM-MSC (3.8 ± 2.7 channels) and DFT groups (5.5 ± 1.8 channels) (P < 0.0001 and P= 0.002, respectively). The combined use of hBM-MSC and DFT in a rat model of arterial thrombosis showed additive effect resulting in near-complete resolution of the thrombus.
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Wang, Xin; Ma, Feng-Xia; Lu, Shi-Hong; Chi, Ying; Chen, Fang; Li, Xue; Li, Juan-Juan; Du, Wen-Jing; Feng, Ying; Cui, Jun-Jie; Song, Bao-Quan; Han, Zhong-Chao
2014-06-01
This study was aimed to investigate the effects of rapamycin on biological function and autophagy of bone marrow mesenchymal stem cells (BM-MSC) from patients with aplastic anemia so as to provide experimental basis for the clinical treatment of aplastic anemia (AA) with rapamycin. BM-MSC were treated with different concentrations of rapamycin (0, 10, 50, 100 nmol/L) for 48 h, the expression of LC3B protein was detected by Western blot to observe the effect of rapamycin on cell autophagy; cell apoptosis and cell cycles were detected by flow cytometry; the proliferation of BM-MSC of AA patients was measured by cell counting kit-8; the adipogenic differentiation of BM-MSC were tested by oil red O staining after adipogenic induction for 2 weeks; the adipogenic related genes (LPL, CFD, PPARγ) were detected by real-time PCR. The results showed that the proliferation and adipogenesis of BM-MSC of AA patients were inhibited by rapamycin. Moreover, the autophagy and apoptosis of BM-MSC were increased by rapamycin in a dose-dependent way.Rapamycin arrested the BM-MSC in G0/G1 phase and prevented them into S phase (P < 0.05). It is concluded that rapamycin plays an critical role in inhibiting cell proliferation, cell cycles, and adipogenesis, these effects may be related with the autophagy activation and mTOR inhibition resulting from rapamycin.
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Gilz-Activin A as a Novel Signaling Axis Orchestrating Mesenchymal Stem Cell and Th17 Cell Interplay
Luz-Crawford, Patricia; Espinosa-Carrasco, Gabriel; Ipseiz, Natacha; Contreras, Rafael; Tejedor, Gautier; Medina, Daniel A.; Vega-Letter, Ana-Maria; Ngo, Devi; Morand, Eric F.; Pène, Jérôme; Hernandez, Javier; Jorgensen, Christian; Djouad, Farida
2018-01-01
Mesenchymal stem cells (MSC) are highly immunosuppressive cells able to reduce chronic inflammation through the active release of mediators. Recently, we showed that glucocorticoid-induced leucine zipper (Gilz) expression by MSC is involved in their therapeutic effect by promoting the generation of regulatory T cells. However, the mechanisms underlying this pivotal role of Gilz remain elusive. Methods and Results In this study, we have uncovered evidence that Gilz modulates the phenotype and function of Th1 and Th17 cells likely by upregulating the level of Activin A and NO2 secreted by MSC. Adoptive transfer experiments sustained this Gilz-dependent suppressive effect of MSC on Th1 and Th17 cell functions. In immunoregulatory MSC, obtained by priming with IFN-γ and TNF-α, Gilz was translocated to the nucleus and bound to the promoters of inos and Activin βA to induce their expression. The increased expression of Activin A directly impacted on Th17 cells fate by repressing their differentiation program through the activation of Smad3/2 and enhancing IL-10 production. Conclusion Our results reveal how Gilz controls inos and Activin βA gene expression to ultimately assign immunoregulatory status to MSC able to repress the pathogenic Th17 cell differentiation program and uncover Activin A as a novel mediator of MSC in this process. PMID:29344311
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Luz-Crawford, Patricia; Espinosa-Carrasco, Gabriel; Ipseiz, Natacha; Contreras, Rafael; Tejedor, Gautier; Medina, Daniel A; Vega-Letter, Ana-Maria; Ngo, Devi; Morand, Eric F; Pène, Jérôme; Hernandez, Javier; Jorgensen, Christian; Djouad, Farida
2018-01-01
Mesenchymal stem cells (MSC) are highly immunosuppressive cells able to reduce chronic inflammation through the active release of mediators. Recently, we showed that glucocorticoid-induced leucine zipper (Gilz) expression by MSC is involved in their therapeutic effect by promoting the generation of regulatory T cells. However, the mechanisms underlying this pivotal role of Gilz remain elusive. Methods and Results In this study, we have uncovered evidence that Gilz modulates the phenotype and function of Th1 and Th17 cells likely by upregulating the level of Activin A and NO 2 secreted by MSC. Adoptive transfer experiments sustained this Gilz-dependent suppressive effect of MSC on Th1 and Th17 cell functions. In immunoregulatory MSC, obtained by priming with IFN-γ and TNF-α, Gilz was translocated to the nucleus and bound to the promoters of inos and Activin βA to induce their expression. The increased expression of Activin A directly impacted on Th17 cells fate by repressing their differentiation program through the activation of Smad3/2 and enhancing IL-10 production. Conclusion Our results reveal how Gilz controls inos and Activin βA gene expression to ultimately assign immunoregulatory status to MSC able to repress the pathogenic Th17 cell differentiation program and uncover Activin A as a novel mediator of MSC in this process.
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da Costa, Milene R; Pizzatti, Luciana; Lindoso, Rafael S; Sant'Anna, Julliana Ferreira; DuRocher, Barbara; Abdelhay, Eliana; Vieyra, Adalberto
2014-06-01
Acute kidney injury (AKI) is one of the more frequent and lethal pathological conditions seen in intensive care units. Currently available treatments are not totally effective but stem cell-based therapies are emerging as promising alternatives, especially the use of mesenchymal stromal cells (MSC), although the signaling pathways involved in their beneficial actions are not fully understood. The objective of this study was to identify signaling networks and key proteins involved in the repair of ischemia by MSC. Using an in vitro model of AKI to investigate paracrine interactions and label-free high definition 2D-NanoESI-MS(E) , differentially expressed proteins were identified in a human renal proximal tubule cell lineage (HK-2) exposed to human MSC (hMSC) after an ischemic insult. In silico analysis showed that hMSC stimulated antiapoptotic activity, normal ROS handling, energy production, cytoskeleton organization, protein synthesis, and cell proliferation. The proteomic data were validated by parallel experiments demonstrating reduced apoptosis in HK-2 cells and recovery of intracellular ATP levels. qRT-PCR for proteins implicated in the above processes revealed that hMSC exerted their effects by stimulating translation, not transcription. Western blotting of proteins associated with ROS and energy metabolism confirmed their higher abundance in HK-2 cells exposed to hMSC. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
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First Apollo 11 Lunar Samples Arrive at the Manned Spacecraft Center (MSC)
NASA Technical Reports Server (NTRS)
1969-01-01
The Apollo 11 mission, the first manned lunar mission, launched from the Kennedy Space Center, Florida via the Marshall Space Flight Center (MSFC) developed Saturn V launch vehicle on July 16, 1969 and safely returned to Earth on July 24, 1969. Aboard the space craft were astronauts Neil A. Armstrong, commander; Michael Collins, Command Module (CM) pilot; and Edwin E. Aldrin Jr., Lunar Module (LM) pilot. The CM, piloted by Michael Collins remained in a parking orbit around the Moon while the LM, named 'Eagle'', carrying astronauts Neil Armstrong and Edwin Aldrin, landed on the Moon. During 2½ hours of surface exploration, the crew collected 47 pounds of lunar surface material for analysis back on Earth. This photograph was taken as the mission's first loaded sample return container arrived at Ellington Air Force Base by air from the Pacific recovery area. The rock box was immediately taken to the Lunar Receiving Laboratory at the Manned Spacecraft Center (MSC) in Houston, Texas. Happily posing for the photograph with the rock container are (L-R) Richard S. Johnston (back), special assistant to the MSC Director; George M. Low, MSC Apollo Spacecraft Program manager; George S. Trimble (back), MSC Deputy Director; Lt. General Samuel C. Phillips, Apollo Program Director, Office of Manned Spaceflight at NASA headquarters; Eugene G. Edmonds, MSC Photographic Technology Laboratory; Dr. Thomas O. Paine, NASA Administrator; and Dr. Robert R. Gilruth, MSC Director.
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Cell therapy in joint disorders.
Counsel, Peter D; Bates, Daniel; Boyd, Richard; Connell, David A
2015-01-01
Articular cartilage possesses poor natural healing mechanisms, and a variety of non-cell-based and cell-based treatments aim to promote regeneration of hyaline cartilage. A review of the literature to December 2013 using PubMed with search criteria including the keywords stem cell, cell therapy, cell transplantation, cartilage, chondral, and chondrogenic. Forty-five articles were identified that employed local mesenchymal stem cell (MSC) therapy for joint disorders in humans. Nine comparative studies were identified, consisting of 3 randomized trials, 5 cohort studies, and 1 case-control study. Clinical review. Level 4. Studies were assessed for stem cell source, method of implantation, comparison groups, and concurrent surgical techniques. Two studies comparing MSC treatment to autologous chondrocyte implantation found similar efficacy. Three studies reported clinical benefits with intra-articular MSC injection over non-MSC controls for cases undergoing debridement with or without marrow stimulation, although a randomized study found no significant clinical difference at 2-year follow-up but reported better 18-month magnetic resonance imaging and histologic scores in the MSC group. No human studies have compared intra-articular MSC therapy to non-MSC techniques for osteoarthritis in the absence of surgery. Mesenchymal stem cell-based therapies appear safe and effective for joint disorders in large animal preclinical models. Evidence for use in humans, particularly, comparison with more established treatments such as autologous chondrocyte implantation and microfracture, is limited.
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Harada, Yohei; Nakasa, Tomoyuki; Mahmoud, Elhussein Elbadry; Kamei, Goki; Adachi, Nobuo; Deie, Masataka; Ochi, Mitsuo
2015-10-01
The present study investigated intra-articular injection of bone-marrow-derived mesenchymal stem cells (MSCs) combined with articulated joint distraction as treatment for osteochondral defects. Large osteochondral defects were created in the weight-bearing area of the medial femoral condyle in rabbit knees. Four weeks after defect creation, rabbits were divided into six groups: control group, MSC group, distraction group, distraction + MSC group, temporary distraction group, and temporary distraction + MSC group. Groups with MSC received intra-articular injection of MSCs. Groups with distraction underwent articulated distraction arthroplasty. Groups with temporary distraction discontinued the distraction after 4 weeks. The rabbits were euthanized at 4, 8, and 12 weeks after treatment except temporary distraction groups which were euthanized at only 12 weeks. Histological scores in the distraction + MSC group were significantly better than in the control, MSC group or distraction group at 4 and 8 weeks, but showed no further improvement. At 12 weeks, the temporary distraction + MSC group showed the best results, demonstrating hyaline cartilage repair with regeneration of the osteochondral junction. In conclusion, joint distraction with intra-articular injection of MSCs promotes early cartilage repair, and compressive loading of the repair tissue after temporary distraction stimulates articular cartilage regeneration. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.