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Sample records for cells exert 3-dimensional

  1. Traction forces exerted by epithelial cell sheets

    Saez, A; Anon, E; Ghibaudo, M; Di Meglio, J-M; Hersen, P; Ladoux, B; Du Roure, O; Silberzan, P; Buguin, A

    2010-01-01

    Whereas the adhesion and migration of individual cells have been well described in terms of physical forces, the mechanics of multicellular assemblies is still poorly understood. Here, we study the behavior of epithelial cells cultured on microfabricated substrates designed to measure cell-to-substrate interactions. These substrates are covered by a dense array of flexible micropillars whose deflection enables us to measure traction forces. They are obtained by lithography and soft replica molding. The pillar deflection is measured by video microscopy and images are analyzed with home-made multiple particle tracking software. First, we have characterized the temporal and spatial distributions of traction forces of cellular assemblies of various sizes. The mechanical force balance within epithelial cell sheets shows that the forces exerted by neighboring cells strongly depend on their relative position in the monolayer: the largest deformations are always localized at the edge of the islands of cells in the active areas of cell protrusions. The average traction stress rapidly decreases from its maximum value at the edge but remains much larger than the inherent noise due to the force resolution of our pillar tracking software, indicating an important mechanical activity inside epithelial cell islands. Moreover, these traction forces vary linearly with the rigidity of the substrate over about two decades, suggesting that cells exert a given amount of deformation rather than a force. Finally, we engineer micropatterned substrates supporting pillars with anisotropic stiffness. On such substrates cellular growth is aligned with respect to the stiffest direction in correlation with the magnitude of the applied traction forces.

  2. Scaffold Free Bio-orthogonal Assembly of 3-Dimensional Cardiac Tissue via Cell Surface Engineering

    Rogozhnikov, Dmitry; O'Brien, Paul J.; Elahipanah, Sina; Yousaf, Muhammad N.

    2016-12-01

    There has been tremendous interest in constructing in vitro cardiac tissue for a range of fundamental studies of cardiac development and disease and as a commercial system to evaluate therapeutic drug discovery prioritization and toxicity. Although there has been progress towards studying 2-dimensional cardiac function in vitro, there remain challenging obstacles to generate rapid and efficient scaffold-free 3-dimensional multiple cell type co-culture cardiac tissue models. Herein, we develop a programmed rapid self-assembly strategy to induce specific and stable cell-cell contacts among multiple cell types found in heart tissue to generate 3D tissues through cell-surface engineering based on liposome delivery and fusion to display bio-orthogonal functional groups from cell membranes. We generate, for the first time, a scaffold free and stable self assembled 3 cell line co-culture 3D cardiac tissue model by assembling cardiomyocytes, endothelial cells and cardiac fibroblast cells via a rapid inter-cell click ligation process. We compare and analyze the function of the 3D cardiac tissue chips with 2D co-culture monolayers by assessing cardiac specific markers, electromechanical cell coupling, beating rates and evaluating drug toxicity.

  3. Traction Stresses Exerted by Adherent Cells: From Angiogenesis to Metastasis

    Reinhart-King, Cynthia

    2010-03-01

    Cells exert traction stresses against their substrate that mediate their ability to sense the mechanical properties of their microenvironment. These same forces mediate cell adhesion, migration and the formation of stable cell-cell contacts during tissue formation. In this talk, I will present our data on the traction stresses generated by endothelial cells and metastatic breast cancer cells focused on understanding the processes of angiogenesis and metastasis, respectively. In the context of capillary formation, our data indicate that the mechanics of the substrate play a critical role in establishing endothelial cell-cell contacts. On more compliant substrates, endothelial cell shape and traction stresses polarize and promote the formation of stable cell-cell contacts. On stiffer substrates, traction stresses are less polarized and cell connectivity is disrupted. These data indicate that the mechanical properties of the microenvironment may drive cell connectivity and the formation of stable cell-cell contacts through the reorientation of traction stresses. In our studies of metastatic cell migration, we have found that traction stresses increase with increasing metastatic potential. We investigated three lines of varying metastatic potential (MCF10A, MCF7 and MDAMB231). MDAMB231, which are the most invasive, exert the most significant forces as measured by Traction Force Microscopy. These data present the possibility that cellular traction stress generation aids in the ability of metastatic cells to migrate through the matrix-dense tumor microenvironment. Such measurements are integral to link the mechanical and chemical microenvironment with the resulting response of the cell in health and disease.

  4. 3-Dimensional Computational Fluid Dynamics Modeling of Solid Oxide Fuel Cell Using Different Fuels

    2011-01-01

    major types of fuel cells in practice are listed below: Polymer Electrolyte Membrane Fuel Cell ( PEMFC ) Alkaline Fuel cell (AFC) Phosphoric Acid...Material Operating Temperature (oC) Efficiency (%) PEMFC H2, Methanol, Formic Acid Hydrated Organic Polymer < 90 40-50 AFC Pure H2 Aqueous

  5. A 3-dimensional human embryonic stem cell (hESC)-derived model to detect developmental neurotoxicity of nanoparticles.

    Hoelting, Lisa; Scheinhardt, Benjamin; Bondarenko, Olesja; Schildknecht, Stefan; Kapitza, Marion; Tanavde, Vivek; Tan, Betty; Lee, Qian Yi; Mecking, Stefan; Leist, Marcel; Kadereit, Suzanne

    2013-04-01

    Nanoparticles (NPs) have been shown to accumulate in organs, cross the blood-brain barrier and placenta, and have the potential to elicit developmental neurotoxicity (DNT). Here, we developed a human embryonic stem cell (hESC)-derived 3-dimensional (3-D) in vitro model that allows for testing of potential developmental neurotoxicants. Early central nervous system PAX6(+) precursor cells were generated from hESCs and differentiated further within 3-D structures. The 3-D model was characterized for neural marker expression revealing robust differentiation toward neuronal precursor cells, and gene expression profiling suggested a predominantly forebrain-like development. Altered neural gene expression due to exposure to non-cytotoxic concentrations of the known developmental neurotoxicant, methylmercury, indicated that the 3-D model could detect DNT. To test for specific toxicity of NPs, chemically inert polyethylene NPs (PE-NPs) were chosen. They penetrated deep into the 3-D structures and impacted gene expression at non-cytotoxic concentrations. NOTCH pathway genes such as HES5 and NOTCH1 were reduced in expression, as well as downstream neuronal precursor genes such as NEUROD1 and ASCL1. FOXG1, a patterning marker, was also reduced. As loss of function of these genes results in severe nervous system impairments in mice, our data suggest that the 3-D hESC-derived model could be used to test for Nano-DNT.

  6. Radiosensitivity of Patient-Derived Glioma Stem Cell 3-Dimensional Cultures to Photon, Proton, and Carbon Irradiation

    Chiblak, Sara; Tang, Zili [German Cancer Consortium, Heidelberg (Germany); Molecular and Translational Radiation Oncology, Heidelberg Ion Therapy Center, Heidelberg Institute of Radiation Oncology, University of Heidelberg Medical School and National Center for Tumor Diseases, German Cancer Research Center, Heidelberg (Germany); Campos, Benito; Gal, Zoltan; Unterberg, Andreas [Division of Neurological Research, Department of Neurosurgery, University of Heidelberg Medical School, Heidelberg (Germany); Debus, Jürgen [German Cancer Consortium, Heidelberg (Germany); Molecular and Translational Radiation Oncology, Heidelberg Ion Therapy Center, Heidelberg Institute of Radiation Oncology, University of Heidelberg Medical School and National Center for Tumor Diseases, German Cancer Research Center, Heidelberg (Germany); Herold-Mende, Christel [Division of Neurological Research, Department of Neurosurgery, University of Heidelberg Medical School, Heidelberg (Germany); Abdollahi, Amir, E-mail: a.amir@dkfz.de [German Cancer Consortium, Heidelberg (Germany); Molecular and Translational Radiation Oncology, Heidelberg Ion Therapy Center, Heidelberg Institute of Radiation Oncology, University of Heidelberg Medical School and National Center for Tumor Diseases, German Cancer Research Center, Heidelberg (Germany)

    2016-05-01

    Purpose: To investigate the radiosensitivity of primary glioma stem cell (GSC) cultures with different CD133 status in a 3-dimensional (3D) model after photon versus proton versus carbon irradiation. Methods and Materials: Human primary GSC spheroid cultures were established from tumor specimens of six consented glioblastoma patients. Human U87MG was used as a classical glioblastoma radioresistant cell line. Cell suspensions were generated by mechanical dissociation of GSC spheroids and embedded in a semi-solid 3D matrix before irradiation. Spheroid-like colonies were manually counted by microscopy. Cells were also recovered and quantified by fluorescence. CD133 expression and DNA damage were evaluated by flow cytometry. Results: The fraction of CD133{sup +} cells varied between 0.014% and 96% in the six GSC cultures and showed a nonsignificant correlation with plating efficiency and survival fractions. The 4 most photon-radioresistant GSC cultures were NCH644, NCH421k, NCH441, and NCH636. Clonogenic survival for proton irradiation revealed relative biologic effectiveness (RBE) in the range of 0.7-1.20. However, carbon irradiation rendered the photon-resistant GSC cultures sensitive, with average RBE of 1.87-3.44. This effect was partly attributed to impaired capability of GSC to repair carbon ion–induced DNA double-strand breaks as determined by residual DNA repair foci. Interestingly, radiosensitivity of U87 cells was comparable to GSC cultures using clonogenic survival as the standard readout. Conclusions: Carbon irradiation is effective in GSC eradication with similar RBE ranges approximately 2-3 as compared with non-stem GSC cultures (U87). Our data strongly suggest further exploration of GSC using classic radiobiology endpoints such as the here-used 3D clonogenic survival assay and integration of additional GSC-specific markers.

  7. Radiosensitivity of Patient-Derived Glioma Stem Cell 3-Dimensional Cultures to Photon, Proton, and Carbon Irradiation

    Chiblak, Sara; Tang, Zili; Campos, Benito; Gal, Zoltan; Unterberg, Andreas; Debus, Jürgen; Herold-Mende, Christel; Abdollahi, Amir

    2016-01-01

    Purpose: To investigate the radiosensitivity of primary glioma stem cell (GSC) cultures with different CD133 status in a 3-dimensional (3D) model after photon versus proton versus carbon irradiation. Methods and Materials: Human primary GSC spheroid cultures were established from tumor specimens of six consented glioblastoma patients. Human U87MG was used as a classical glioblastoma radioresistant cell line. Cell suspensions were generated by mechanical dissociation of GSC spheroids and embedded in a semi-solid 3D matrix before irradiation. Spheroid-like colonies were manually counted by microscopy. Cells were also recovered and quantified by fluorescence. CD133 expression and DNA damage were evaluated by flow cytometry. Results: The fraction of CD133"+ cells varied between 0.014% and 96% in the six GSC cultures and showed a nonsignificant correlation with plating efficiency and survival fractions. The 4 most photon-radioresistant GSC cultures were NCH644, NCH421k, NCH441, and NCH636. Clonogenic survival for proton irradiation revealed relative biologic effectiveness (RBE) in the range of 0.7-1.20. However, carbon irradiation rendered the photon-resistant GSC cultures sensitive, with average RBE of 1.87-3.44. This effect was partly attributed to impaired capability of GSC to repair carbon ion–induced DNA double-strand breaks as determined by residual DNA repair foci. Interestingly, radiosensitivity of U87 cells was comparable to GSC cultures using clonogenic survival as the standard readout. Conclusions: Carbon irradiation is effective in GSC eradication with similar RBE ranges approximately 2-3 as compared with non-stem GSC cultures (U87). Our data strongly suggest further exploration of GSC using classic radiobiology endpoints such as the here-used 3D clonogenic survival assay and integration of additional GSC-specific markers.

  8. Construction of 3-dimensional ZnO-nanoflower structures for high quantum and photocurrent efficiency in dye sensitized solar cell

    Kilic, Bayram, E-mail: bkilic@yalova.edu.tr [Yalova University, Department of Energy Systems Engineering, Faculty of Engineering, 77100 Yalova (Turkey); Günes, Taylan; Besirli, Ilknur; Sezginer, Merve [Yalova University, Department of Energy Systems Engineering, Faculty of Engineering, 77100 Yalova (Turkey); Tuzemen, Sebahattin [Department of Physics, Faculty of Science, Atatürk University, Erzurum 25240 (Turkey)

    2014-11-01

    Graphical abstract: - Highlights: • The structural and optical characterizations of ZnO nanoflowers were carried out on ITO by hydrothermal method. • Dye sensitized solar cell based ZnO nanoflowers were constructed on substrate. • The surface morphology effect on quantum efficiency and solar conversion efficiency were investigated. - Abstract: 3-dimensional ZnO nanoflower were obtained on FTO (F:SnO{sub 2}) substrate by hydrothermal method in order to produce high efficiency dye sensitized solar cells (DSSCs). We showed that nanoflowers structures have nanoscale branches that stretch to fill gaps on the substrate and these branches of nano-leaves provide both a larger surface area and a direct pathway for electron transport along the channels. It was found that the solar conversion efficiency and quantum efficiency (QE) or incident photon to current conversion efficiencies (IPCE) is highly dependent on nanoflower surface due to high electron injection process. The highest solar conversion efficiency of 5.119 and QE of 60% was obtained using ZnO nanoflowers/N719 dye/I{sup −}/I{sup −}{sub 3} electrolyte. In this study, three dimensional (3D)-nanoflower and one dimensional (1D)-nanowires ZnO nanostructures were also compared against each other in respect to solar conversion efficiency and QE measurements. In the case of the 1D-ZnO nanowire conversion efficiency (η) of 2.222% and IPCE 47% were obtained under an illumination of 100 mW/cm{sup 2}. It was confirmed that the performance of the 3D-nanoflowers was better than about 50% that of the 1D-nanowire dye-sensitized solar cells.

  9. Chondroregulatory action of prolactin on proliferation and differentiation of mouse chondrogenic ATDC5 cells in 3-dimensional micromass cultures

    Seriwatanachai, Dutmanee; Krishnamra, Nateetip; Charoenphandhu, Narattaphol

    2012-01-01

    Highlights: ► Mouse chondrogenic ATDC5 cells expressed PRL receptor mRNAs and proteins. ► Low PRL concentration (10 ng/mL) increased chondrocyte viability and differentiation. ► Higher PRL concentrations (⩾100 ng/mL) decreased viability and increased apoptosis. -- Abstract: A recent investigation in lactating rats has provided evidence that the lactogenic hormone prolactin (PRL) increases endochondral bone growth and bone elongation, presumably by accelerating apoptosis of hypertrophic chondrocytes in the growth plate and/or subsequent chondrogenic matrix mineralization. Herein, we demonstrated the direct chondroregulatory action of PRL on proliferation, differentiation and apoptosis of chondrocytes in 3-dimensional micromass culture of mouse chondrogenic ATDC5 cell line. The results showed that ATDC5 cells expressed PRL receptor (PRLR) transcripts, and responded typically to PRL by downregulating PRLR expression. Exposure to a low PRL concentration of 10 ng/mL, comparable to the normal levels in male and non-pregnant female rats, increased chondrocyte viability, differentiation, proteoglycan accumulation, and mRNA expression of several chondrogenic differentiation markers, such as Sox9, ALP and Hspg2. In contrast, high PRL concentrations of ⩾100 ng/mL, comparable to the levels in pregnancy or lactation, decreased chondrocyte viability by inducing apoptosis, with no effect on chondrogenic marker expression. It could be concluded that chondrocytes directly but differentially responded to non-pregnant and pregnant/lactating levels of PRL, thus suggesting the stimulatory effect of PRL on chondrogenesis in young growing individuals, and supporting the hypothesis of hypertrophic chondrocyte apoptosis in the growth plate of lactating rats.

  10. Chondroregulatory action of prolactin on proliferation and differentiation of mouse chondrogenic ATDC5 cells in 3-dimensional micromass cultures

    Seriwatanachai, Dutmanee [Center of Calcium and Bone Research (COCAB), Faculty of Science, Mahidol University, Bangkok (Thailand); Krishnamra, Nateetip [Center of Calcium and Bone Research (COCAB), Faculty of Science, Mahidol University, Bangkok (Thailand); Department of Physiology, Faculty of Science, Mahidol University, Bangkok (Thailand); Charoenphandhu, Narattaphol, E-mail: naratt@narattsys.com [Center of Calcium and Bone Research (COCAB), Faculty of Science, Mahidol University, Bangkok (Thailand); Department of Physiology, Faculty of Science, Mahidol University, Bangkok (Thailand)

    2012-03-30

    Highlights: Black-Right-Pointing-Pointer Mouse chondrogenic ATDC5 cells expressed PRL receptor mRNAs and proteins. Black-Right-Pointing-Pointer Low PRL concentration (10 ng/mL) increased chondrocyte viability and differentiation. Black-Right-Pointing-Pointer Higher PRL concentrations ( Greater-Than-Or-Slanted-Equal-To 100 ng/mL) decreased viability and increased apoptosis. -- Abstract: A recent investigation in lactating rats has provided evidence that the lactogenic hormone prolactin (PRL) increases endochondral bone growth and bone elongation, presumably by accelerating apoptosis of hypertrophic chondrocytes in the growth plate and/or subsequent chondrogenic matrix mineralization. Herein, we demonstrated the direct chondroregulatory action of PRL on proliferation, differentiation and apoptosis of chondrocytes in 3-dimensional micromass culture of mouse chondrogenic ATDC5 cell line. The results showed that ATDC5 cells expressed PRL receptor (PRLR) transcripts, and responded typically to PRL by downregulating PRLR expression. Exposure to a low PRL concentration of 10 ng/mL, comparable to the normal levels in male and non-pregnant female rats, increased chondrocyte viability, differentiation, proteoglycan accumulation, and mRNA expression of several chondrogenic differentiation markers, such as Sox9, ALP and Hspg2. In contrast, high PRL concentrations of Greater-Than-Or-Slanted-Equal-To 100 ng/mL, comparable to the levels in pregnancy or lactation, decreased chondrocyte viability by inducing apoptosis, with no effect on chondrogenic marker expression. It could be concluded that chondrocytes directly but differentially responded to non-pregnant and pregnant/lactating levels of PRL, thus suggesting the stimulatory effect of PRL on chondrogenesis in young growing individuals, and supporting the hypothesis of hypertrophic chondrocyte apoptosis in the growth plate of lactating rats.

  11. Anatomical region-dependent enhancement of 3-dimensional chondrogenic differentiation of human mesenchymal stem cells by soluble meniscus extracellular matrix.

    Rothrauff, Benjamin B; Shimomura, Kazunori; Gottardi, Riccardo; Alexander, Peter G; Tuan, Rocky S

    2017-02-01

    decellularized meniscus tissue may promote homologous differentiation of progenitor cells, thereby enhancing fibrocartilage formation within a meniscal lesion. However, the meniscus possesses regional variation in ultrastructure, biochemical composition, and cell phenotype, which may affect the bioactivity of soluble ECM derived from different regions of decellularized menisci. In this study, we demonstrate that urea-extracted fractions of ECM derived from the inner and outer regions of menisci enhance chondrogenesis in mesenchymal stem cells seeded in 3-dimensional photocrosslinkable hydrogels and that this effect is more strongly mediated by inner meniscal ECM. These findings suggest region-specific bioactivity of decellularized meniscal ECM. Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  12. Clinical application of human adipose tissue-derived mesenchymal stem cells in progressive hemifacial atrophy (Parry-Romberg disease) with microfat grafting techniques using 3-dimensional computed tomography and 3-dimensional camera.

    Koh, Kyung Suk; Oh, Tae Suk; Kim, Hoon; Chung, In Wook; Lee, Kang Woo; Lee, Hyo Bo; Park, Eun Jung; Jung, Jae Seob; Shin, Il Seob; Ra, Jeong Chan; Choi, Jong Woo

    2012-09-01

    Parry-Romberg disease is a rare condition that results in progressive hemifacial atrophy, involving the skin, dermis, subcutaneous fat, muscle, and, finally, cartilage and bone. Patients have been treated with dermofat or fat grafts or by microvascular free flap transfer. We hypothesized that adipose-derived stem cells (ASCs) may improve the results of microfat grafting through enhancing angiogenesis. We evaluated the utility of ASC in microfat grafting of patients with Parry-Romberg disease by measuring the change in the hemifacial volumes after injection of ASCs with microfat grafts or microfat grafts alone. In April 2008, this investigation was approved by the Korean Food and Drug Administration and the institutional review board of the Asan Medical Center (Seoul, Korea) that monitor investigator-initiated trials. Between May 2008 and January 2009, 10 volunteers with Parry-Romberg disease (5 men and 5 women; mean age, 28 y) were recruited; 5 received ASC and microfat grafts and 5 received microfat grafts only. The mean follow-up period was 15 months. Adipose-derived stem cells were obtained from abdominal fat by liposuction and were cultured for 2 weeks. On day 14, patients were injected with fat grafts alone or plus (in the test group) 1 × 10 ASCs. Patients were evaluated postoperatively using a 3-dimensional camera and 3-dimensional CT scans, and grafted fat volumes were objectively calculated. Successful outcomes were evident in all 5 patients receiving microfat grafts and ASCs, and the survival of grafted fat was better than in patients receiving microfat grafts alone. Before surgery, the mean difference between ipsilateral and contralateral hemiface volume in patients receiving microfat grafts and ASCs was 21.71 mL decreasing to 4.47 mL after surgery. Overall resorption in this ASC group was 20.59%. The mean preoperative difference in hemiface volume in those receiving microfat grafts alone was 8.32 mL decreasing to 3.89 mL after surgery. Overall

  13. The Effect of Pulsatile Flow on bMSC-Derived Endothelial-Like Cells in a Small-Sized Artificial Vessel Made by 3-Dimensional Bioprinting

    Kang Woog Lee

    2018-01-01

    Full Text Available Replacement of small-sized vessels is still challenging. This study is aimed at investigating the possibility of small-sized artificial vessels made by 3-dimensional bioprinting and the effect of pulsatile flow on bMSC-derived endothelial-like cells. Cells were harvested from rabbit bone marrow and primary cultured with or without growth factors. Endothelial differentiation was confirmed by the Matrigel tube formation assay, Western blot, and qRT-PCR. In addition, embedment of endothelial-like cells in an artificial vessel was made by 3-dimensional bioprinting, and the pulsatile flow was performed. For pumped and nonpumped groups, qRT-PCR was performed on CD31 and VE-cadherin gene expression. Endothelial-like cells showed increased gene expression of CD31 and VE-cadherin, and tube formation is observed at each week. Endothelial-like cells grow well in a small-sized artificial vessel made by 3-dimensional bioprinting and even express higher endothelial cell markers when they undergo pulsatile flow condition. Moreover, the pulsatile flow condition gives a positive effect for cell observation not only on the sodium alginate hydrogel layer but also on the luminal surface of the artificial vessel wall. We have developed an artificial vessel, which is a mixture of cells and carriers using a 3-dimensional bioprinting method, and applied pulsatile flow using a peristaltic pump, and we also demonstrated cell growth and differentiation into endothelial cells. This study suggests guidelines regarding a small-sized artificial vessel in the field of tissue engineering.

  14. Preoperative (3-dimensional) computed tomography lung reconstruction before anatomic segmentectomy or lobectomy for stage I non-small cell lung cancer.

    Chan, Ernest G; Landreneau, James R; Schuchert, Matthew J; Odell, David D; Gu, Suicheng; Pu, Jiantao; Luketich, James D; Landreneau, Rodney J

    2015-09-01

    Accurate cancer localization and negative resection margins are necessary for successful segmentectomy. In this study, we evaluate a newly developed software package that permits automated segmentation of the pulmonary parenchyma, allowing 3-dimensional assessment of tumor size, location, and estimates of surgical margins. A pilot study using a newly developed 3-dimensional computed tomography analytic software package was performed to retrospectively evaluate preoperative computed tomography images of patients who underwent segmentectomy (n = 36) or lobectomy (n = 15) for stage 1 non-small cell lung cancer. The software accomplishes an automated reconstruction of anatomic pulmonary segments of the lung based on bronchial arborization. Estimates of anticipated surgical margins and pulmonary segmental volume were made on the basis of 3-dimensional reconstruction. Autosegmentation was achieved in 72.7% (32/44) of preoperative computed tomography images with slice thicknesses of 3 mm or less. Reasons for segmentation failure included local severe emphysema or pneumonitis, and lower computed tomography resolution. Tumor segmental localization was achieved in all autosegmented studies. The 3-dimensional computed tomography analysis provided a positive predictive value of 87% in predicting a marginal clearance greater than 1 cm and a 75% positive predictive value in predicting a margin to tumor diameter ratio greater than 1 in relation to the surgical pathology assessment. This preoperative 3-dimensional computed tomography analysis of segmental anatomy can confirm the tumor location within an anatomic segment and aid in predicting surgical margins. This 3-dimensional computed tomography information may assist in the preoperative assessment regarding the suitability of segmentectomy for peripheral lung cancers. Published by Elsevier Inc.

  15. Melittin exerts an antitumor effect on non‑small cell lung cancer cells.

    Zhang, Su-Fang; Chen, Zhe

    2017-09-01

    Lung cancer accounts for a significant percentage of all cancer‑associated mortalities in men and women, with non‑small cell lung cancer being the most frequently occurring type of lung cancer. Melittin is the principal active component of apitoxin (bee venom) that has been reported to exert anti‑chronic inflammatory and anti‑cancer effects. In the present study, the antitumor effect of melittin was evaluated using in vivo and in vitro analyses. The results demonstrated that melittin significantly inhibited the epidermal growth factor‑induced invasion and migration of non‑small cell lung cancer cells. Subcutaneous injection of melittin at doses of 1 and 10 mg/kg significantly suppressed non‑small cell lung cancer tumor growth by 27 and 61%, respectively. In addition, melittin significantly inhibited the secretion of vascular endothelial growth factor (VEGF) in non‑small cell lung cancer cells. Furthermore, melittin decreased the protein expression of VEGF and hypoxia‑inducible factor 1‑α. Therefore, the antitumor activity of melittin may be associated with the anti‑angiogenic actions of inhibiting the VEGF and hypoxia‑inducible factor signaling pathways.

  16. The endoplasmic reticulum exerts control over organelle streaming during cell expansion.

    Stefano, Giovanni; Renna, Luciana; Brandizzi, Federica

    2014-03-01

    Cytoplasmic streaming is crucial for cell homeostasis and expansion but the precise driving forces are largely unknown. In plants, partial loss of cytoplasmic streaming due to chemical and genetic ablation of myosins supports the existence of yet-unknown motors for organelle movement. Here we tested a role of the endoplasmic reticulum (ER) as propelling force for cytoplasmic streaming during cell expansion. Through quantitative live-cell analyses in wild-type Arabidopsis thaliana cells and mutants with compromised ER structure and streaming, we demonstrate that cytoplasmic streaming undergoes profound changes during cell expansion and that it depends on motor forces co-exerted by the ER and the cytoskeleton.

  17. Dual effects exerted in vitro by micromolar concentrations of deoxynivalenol on undifferentiated caco-2 cells.

    Manda, Gina; Mocanu, Mihaela Andreea; Marin, Daniela Eliza; Taranu, Ionelia

    2015-02-16

    Contamination of crops used for food and feed production with Fusarium mycotoxins, such as deoxynivalenol (DON), raise important health and economic issues all along the food chain. Acute exposure to high DON concentrations can alter the intestinal barrier, while chronic exposure to lower doses may exert more subtle effects on signal transduction pathways, leading to disturbances in cellular homeostasis. Using real-time cellular impedance measurements, we studied the effects exerted in vitro by low concentrations of DON (0.37-1.50 μM), relevant for mycotoxin-contaminated food, on the proliferation of undifferentiated Caco-2 cells presenting a tumorigenic phenotype. A 1.5 μM concentration of DON maintained cell adherence of non-proliferating Caco-2 cells, whilst arresting the growth of actively proliferating cells compared with control Caco-2 cells in vitro. At 0.37 μM, DON enhanced Caco-2 cell metabolism, thereby triggering a moderate increase in cell proliferation. The results of the current study suggested that low concentrations of DON commonly detected in food may either limit or sustain the proliferation of colon cancer cells, depending on their proliferation status and on DON concentration. Soluble factors released by Lactobacillus strains can partially counteract the inhibitory action of DON on actively proliferating colon cancer cells. The study also emphasized that real-time cellular impedance measurements were a valuable tool for investigating the dynamics of cellular responses to xenobiotics.

  18. Dual Effects Exerted in Vitro by Micromolar Concentrations of Deoxynivalenol on Undifferentiated Caco-2 Cells

    Gina Manda

    2015-02-01

    Full Text Available Contamination of crops used for food and feed production with Fusarium mycotoxins, such as deoxynivalenol (DON, raise important health and economic issues all along the food chain. Acute exposure to high DON concentrations can alter the intestinal barrier, while chronic exposure to lower doses may exert more subtle effects on signal transduction pathways, leading to disturbances in cellular homeostasis. Using real-time cellular impedance measurements, we studied the effects exerted in vitro by low concentrations of DON (0.37–1.50 μM, relevant for mycotoxin-contaminated food, on the proliferation of undifferentiated Caco-2 cells presenting a tumorigenic phenotype. A 1.5 μM concentration of DON maintained cell adherence of non-proliferating Caco-2 cells, whilst arresting the growth of actively proliferating cells compared with control Caco-2 cells in vitro. At 0.37 μM, DON enhanced Caco-2 cell metabolism, thereby triggering a moderate increase in cell proliferation. The results of the current study suggested that low concentrations of DON commonly detected in food may either limit or sustain the proliferation of colon cancer cells, depending on their proliferation status and on DON concentration. Soluble factors released by Lactobacillus strains can partially counteract the inhibitory action of DON on actively proliferating colon cancer cells. The study also emphasized that real-time cellular impedance measurements were a valuable tool for investigating the dynamics of cellular responses to xenobiotics.

  19. Combining 3-dimensional degradable electrostatic spinning scaffold and dental follicle cells to build peri-implant periodontium

    Ximu Zhang

    2013-01-01

    Full Text Available Introduction: Some inevitable problems, such as concentrated bite force and lacked ability of self-renewal, are proved to be the major challenge in the management of implants failures. Thus, it is meaningful to find an ideal dental implant harboring its own peri-implant periodontium, just as the natural teeth. Various studies attempted to reconstruct the periodontium around implants, but unfortunately, it was previously revealed that the artificial periodotium around implants was just a wilderness of fibers, while without the physiological function of natural periodontium, like sensory and homeostatic. The Hypothesis: In this paper, we propose a hypothesis that a modified three-dimensional scaffold with reconstructed peri-implant tissues can be a network for stem cells differentiation. After seeded on the scaffold, stem cells produce various growth factors and differentiate to different orientations in places necessary. This hypothesis, if proven to be valid, will offer a novel and effective therapy for the restoration of missing teeth by implant. Evaluation of the Hypothesis: The scaffold involves three different tissues. Though degradation rate of electrospinning scaffold is under control, its degradation rate should be in consistent with the generation of three tissues. Therefore, the relative experiments are necessary to define the best rate of degradation. Further verification is necessary to check whether the rebuilt cementum, bone and periodontium are strong enough to keep the implant stable and maintain its function.

  20. Intensity-Modulated Radiotherapy versus 3-Dimensional Conformal Radiotherapy Strategies for Locally Advanced Non-Small-Cell Lung Cancer

    Uğur Selek

    2014-12-01

    Full Text Available Chemoradiotherapy is the current standard of care in patients with advanced inoperable stage IIIA or IIIB non-small cell lung cancer (NSCLC. Three-dimensional radiotherapy (3DCRT has been a trusted method for a long time and has well-known drawbacks, most of which could be improved by Intensity Modulated Radiotherapy (IMRT. IMRT is not currently the standard treatment of locally advanced NSCLC, but almost all patients could benefit to a degree in organ at risk sparing, dose coverage conformality, or dose escalation. The most critical step for a radiation oncology department is to strictly evaluate its own technical and physical capabilities to determine the ability of IMRT to deliver an optimal treatment plan. This includes calculating the internal tumor motion (ideally 4DCT or equivalent techniques, treatment planning software with an up-to-date heterogeneity correction algorithm, and daily image guidance. It is crucial to optimise and individualise the therapeutic ratio for each patient during the decision of 3DCRT versus IMRT. The current literature rationalises the increasing use of IMRT, including 4D imaging plus PET/CT, and encourages the applicable knowledge-based and individualised dose escalation using advanced daily image-guided radiotherapy.

  1. Psychological stress exerts an adjuvant effect on skin dendritic cell functions in vivo.

    Saint-Mezard, Pierre; Chavagnac, Cyril; Bosset, Sophie; Ionescu, Marius; Peyron, Eric; Kaiserlian, Dominique; Nicolas, Jean-Francois; Bérard, Frédéric

    2003-10-15

    Psychological stress affects the pathophysiology of infectious, inflammatory, and autoimmune diseases. However, the mechanisms by which stress could modulate immune responses in vivo are poorly understood. In this study, we report that application of a psychological stress before immunization exerts an adjuvant effect on dendritic cell (DC), resulting in increased primary and memory Ag-specific T cell immune responses. Acute stress dramatically enhanced the skin delayed-type hypersensitivity reaction to haptens, which is mediated by CD8(+) CTLs. This effect was due to increased migration of skin DCs, resulting in augmented CD8(+) T cell priming in draining lymph nodes and enhanced recruitment of CD8(+) T cell effectors in the skin upon challenge. This adjuvant effect of stress was mediated by norepinephrine (NE), but not corticosteroids, as demonstrated by normalization of the skin delayed-type hypersensitivity reaction and DC migratory properties following selective depletion of NE. These results suggest that release of NE by sympathetic nerve termini during a psychological stress exerts an adjuvant effect on DC by promoting enhanced migration to lymph nodes, resulting in increased Ag-specific T cell responses. Our findings may open new ways in the treatment of inflammatory diseases, e.g., psoriasis, allergic contact dermatitis, and atopic dermatitis.

  2. Incorporating pTGF-β1/calcium phosphate nanoparticles with fibronectin into 3-dimensional collagen/chitosan scaffolds: Efficient, sustained gene delivery to stem cells for chondrogenic differentiation

    X Cao

    2012-02-01

    Full Text Available The objective of this study was to prepare a 3-dimensional nanoparticle gene delivery system (3D-NGDS based on collagen/chitosan scaffolds, in which plasmid transforming growth factor beta 1 (TGF-β1/calcium phosphate nanoparticles mixed with fibronectin (FN were used to transfect mesenchymal stem cells (MSCs. Scanning electron microscopy was used to characterise the microstructure of 3-dimensional collagen/chitosan scaffolds. An analysis performed to quantify the TGF-b1 concentrations in MSC cultures revealed that the MSCs transfected with the 3D-NGDS showed remarkably high levels of TGF-b1 over long periods, retaining a concentration of TGF-b1 of approximately 10 ng/mL within two weeks, with the highest level (12.6 ng/mL being observed on the 6th day. An immunohistochemistry analysis for collagen type II revealed that much higher production of collagen II from the 9th to 15th day was observed in the 3D-NGDS-transfected MSCs than that in MSCs transfected by the Lipofectamine 2000 method. The glycosaminoglycan content of the 3D-NGDS was comparable to those treated with TGF-β1 as well as TGF-β1 plus dexamethasone, and was significantly higher than those treated with free plasmid and Lipofectamine 2000. A remarkable type I collagen expression inhibition of the 3D-NGDS at day 21 was observed via ELISA. These results suggested that transfection with the 3D-NGDS could successfully induce MSC chondrogenic differentiation in vitro without dexamethasone. In summary, the 3D-NGDS could be developed into a promising alternative method to transfer exogenous nucleic acid to MSCs in clinical trials.

  3. Leading research report for fiscal 1998. Research and study of 3-dimensional cell structure module engineering; 1998 nendo sendo chosa kenkyu hokokusho. Sanjigen saibo soshiki module kogaku chosa kenkyu

    NONE

    1999-03-01

    For the formation of cellular tissues to replace bionic tissues, researches were conducted about technologies of forming bionic tissue modules by culturing various kinds of cells. As for the materials and methods for constructing cellular tissues, researches were conducted about the trends of research and development of 3-dimensional tissue culturing matrices and materials for micromanipulation. As for the development of technologies for the functionalization of 3-dimensionally structured cells, research and study were conducted about the technology of 3-dimensional cell structure organization through application of physical stimulation, the biochemical technology of differentiation inducing, and the differentiation inducing technology for hetero tissue culturing. As for the development of technologies for evaluation using 3-dimensionally structured cells, light CT (computer tomography), analysis and evaluation using spectroscopy and the like, feasibility of the biochemical analysis of the cell state using biosensors, technologies for measuring the secretion of carcinogenic and toxic substances, etc., were studied. In addition, the development of organic models to replace test animals, industrial evolution of 3-dimensional tissue module engineering, etc., were investigated. (NEDO)

  4. Interleukin-1 exerts distinct actions on different cell types of the brain in vitro

    Ying An

    2011-01-01

    Full Text Available Ying An, Qun Chen, Ning QuanDepartment of Oral Biology, Ohio State University, Columbus, OH, USAAbstract: Interleukin-1 (IL-1 is a critical neuroinflammatory mediator in the central nervous system (CNS. In this study, we investigated the effect of IL-1 on inducing inflammation-related gene expression in three astrocyte, two microglial, and one brain endothelial cell line. Interleukin-1 beta (IL-1β is found to be produced by the two microglial cell lines constitutively, but these cells do not respond to IL-1β stimulation. The three astrocyte cell lines responded to IL-1ß stimulation by expressing MCP-1, CXCL-1, and VCAM-1, but different subtypes of astrocytes exhibited different expression profiles after IL-1β stimulation. The brain endothelial cells showed strongest response to IL-1β by producing MCP-1, CXCL-1, VCAM-1, ICAM-1, IL-6, and COX-2 mRNA. The induction of endothelial COX-2 mRNA is shown to be mediated by p38 MAPK pathway, whereas the induction of other genes is mediated by the NF-κB pathway. These results demonstrate that IL-1 exerts distinct cell type-specific action in CNS cells and suggest that IL-1-mediated neuroinflammation is the result of the summation of multiple responses from different cell types in the CNS to IL-1.Keywords: astrocyte, microglia, endothelial cells, signal transduction pathways, gene expression 

  5. Leiomyoma Cells in 3-Dimensional Cultures Demonstrate an Attenuated Response to Fasudil, a Rho-Kinase Inhibitor, When Compared to 2-Dimensional Cultures

    Malik, Minnie; Britten, Joy; Segars, James

    2014-01-01

    Uterine leiomyomata are common benign tumors in women of reproductive age and demonstrate an attenuated response to mechanical signaling that involves Rho and integrins. To further characterize the impairment in Rho signaling, we studied the effect of Rho-kinase inhibitor, fasudil, on extracellular matrix production, in 2-dimensional (2D) and 3-dimensional (3D) cultures of leiomyoma and myometrial cells. Leiomyoma 2D cultures demonstrated a rapid decrease in gene transcripts and protein for fibronectin, procollagen 1A, and versican. In 3D cultures, fibronectin and procollagen 1A proteins demonstrated increased levels at lower concentrations of fasudil, followed by a concentration-dependent decrease. Versican protein increased up to 3-fold, whereas fibromodulin demonstrated a significant decrease of 1.92-fold. Myometrial 2D or 3D cultures demonstrated a decrease in all proteins after 72 hours of treatment. The 3D leiomyoma cultures demonstrated a significant increase in active RhoA, followed by a concentration-dependent decrease at higher concentrations. A concentration-dependent increase in phospho-extracellular regulated signal kinase and proapoptotic protein Bax was observed in 3D leiomyoma cultures. Fasudil relaxed the contraction of the 3D collagen gels caused by myometrium and leiomyoma cell growth. These findings indicate that the altered state of Rho signaling in leiomyoma was more clearly observed in 3D cultures. The results also suggest that fasudil may have clinical applicability for treatment of uterine leiomyoma. PMID:25084783

  6. Resveratrol Exerts Dosage and Duration Dependent Effect on Human Mesenchymal Stem Cell Development

    Peltz, Lindsay; Gomez, Jessica; Marquez, Maribel; Alencastro, Frances; Atashpanjeh, Negar; Quang, Tara; Bach, Thuy; Zhao, Yuanxiang

    2012-01-01

    Studies in the past have illuminated the potential benefit of resveratrol as an anticancer (pro-apoptosis) and life-extending (pro-survival) compound. However, these two different effects were observed at different concentration ranges. Studies of resveratrol in a wide range of concentrations on the same cell type are lacking, which is necessary to comprehend its diverse and sometimes contradictory cellular effects. In this study, we examined the effects of resveratrol on cell self-renewal and differentiation of human mesenchymal stem cells (hMSCs), a type of adult stem cells that reside in a number of tissues, at concentrations ranging from 0.1 to 10 µM after both short- and long-term exposure. Our results reveal that at 0.1 µM, resveratrol promotes cell self-renewal by inhibiting cellular senescence, whereas at 5 µM or above, resveratrol inhibits cell self-renewal by increasing senescence rate, cell doubling time and S-phase cell cycle arrest. At 1 µM, its effect on cell self-renewal is minimal but after long-term exposure it exerts an inhibitory effect, accompanied with increased senescence rate. At all concentrations, resveratrol promotes osteogenic differentiation in a dosage dependent manner, which is offset by its inhibitory effect on cell self-renewal at high concentrations. On the contrary, resveratrol suppresses adipogenic differentiation during short-term exposure but promotes this process after long-term exposure. Our study implicates that resveratrol is the most beneficial to stem cell development at 0.1 µM and caution should be taken in applying resveratrol as an anticancer therapeutic agent or nutraceutical supplement due to its dosage dependent effect on hMSCs. PMID:22615926

  7. Comparison of Toxicity Between Intensity-Modulated Radiotherapy and 3-Dimensional Conformal Radiotherapy for Locally Advanced Non-small-cell Lung Cancer.

    Ling, Diane C; Hess, Clayton B; Chen, Allen M; Daly, Megan E

    2016-01-01

    The role of intensity-modulated radiotherapy (IMRT) in reducing treatment-related toxicity for locally advanced non-small-cell lung cancer (NSCLC) remains incompletely defined. We compared acute toxicity and oncologic outcomes in a large cohort of patients treated with IMRT or 3-dimensional conformal radiotherapy (3-DCRT), with or without elective nodal irradiation (ENI). A single-institution retrospective review was performed evaluating 145 consecutive patients with histologically confirmed stage III NSCLC treated with definitive chemoradiotherapy. Sixty-five (44.8%) were treated with 3-DCRT using ENI, 43 (30.0%) with 3-DCRT using involved-field radiotherapy (IFRT), and 37 (25.5%) with IMRT using IFRT. All patients received concurrent chemotherapy. Comparison of acute toxicities by treatment technique (IMRT vs. 3-DCRT) and extent of nodal irradiation (3-DCRT-IFRT vs. 3-DCRT-ENI) was performed for grade 2 or higher esophagitis or pneumonitis, number of acute hospitalizations, incidence of opioid requirement, percutaneous endoscopic gastrostomy utilization, and percentage weight loss during treatment. Local control and overall survival were analyzed by the Kaplan-Meier method. We identified no significant differences in any measures of acute toxicity by treatment technique or extent of nodal irradiation. There was a trend toward lower rates of grade 2 or higher pneumonitis among IMRT patients compared to 3-DCRT patients (5.4% vs. 23.0%; P = .065). Local control and overall survival were similar between cohorts. Acute and subacute toxicities were similar for patients treated with IMRT and with 3-DCRT with or without ENI, with a nonsignificant trend toward a reduction in pneumonitis with IMRT. Larger studies are needed to better define which patients will benefit from IMRT. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. Customized Knee Prosthesis in Treatment of Giant Cell Tumors of the Proximal Tibia: Application of 3-Dimensional Printing Technology in Surgical Design.

    Luo, Wenbin; Huang, Lanfeng; Liu, He; Qu, Wenrui; Zhao, Xin; Wang, Chenyu; Li, Chen; Yu, Tao; Han, Qing; Wang, Jincheng; Qin, Yanguo

    2017-04-07

    BACKGROUND We explored the application of 3-dimensional (3D) printing technology in treating giant cell tumors (GCT) of the proximal tibia. A tibia block was designed and produced through 3D printing technology. We expected that this 3D-printed block would fill the bone defect after en-bloc resection. Importantly, the block, combined with a standard knee joint prosthesis, provided attachments for collateral ligaments of the knee, which can maintain knee stability. MATERIAL AND METHODS A computed tomography (CT) scan was taken of both knee joints in 4 patients with GCT of the proximal tibia. We developed a novel technique - the real-size 3D-printed proximal tibia model - to design preoperative treatment plans. Hence, with the application of 3D printing technology, a customized proximal tibia block could be designed for each patient individually, which fixed the bone defect, combined with standard knee prosthesis. RESULTS In all 4 cases, the 3D-printed block fitted the bone defect precisely. The motion range of the affected knee was 90 degrees on average, and the soft tissue balance and stability of the knee were good. After an average 7-month follow-up, the MSTS score was 19 on average. No sign of prosthesis fracture, loosening, or other relevant complications were detected. CONCLUSIONS This technique can be used to treat GCT of the proximal tibia when it is hard to achieve soft tissue balance after tumor resection. 3D printing technology simplified the design and manufacturing progress of custom-made orthopedic medical instruments. This new surgical technique could be much more widely applied because of 3D printing technology.

  9. Silybin-mediated inhibition of Notch signaling exerts antitumor activity in human hepatocellular carcinoma cells.

    Song Zhang

    Full Text Available Hepatocellular carcinoma (HCC is a global health burden that is associated with limited treatment options and poor patient prognoses. Silybin (SIL, an antioxidant derived from the milk thistle plant (Silybum marianum, has been reported to exert hepatoprotective and antitumorigenic effects both in vitro and in vivo. While SIL has been shown to have potent antitumor activity against various types of cancer, including HCC, the molecular mechanisms underlying the effects of SIL remain largely unknown. The Notch signaling pathway plays crucial roles in tumorigenesis and immune development. In the present study, we assessed the antitumor activity of SIL in human HCC HepG2 cells in vitro and in vivo and explored the roles of the Notch pathway and of the apoptosis-related signaling pathway on the activity of SIL. SIL treatment resulted in a dose- and time-dependent inhibition of HCC cell viability. Additionally, SIL exhibited strong antitumor activity, as evidenced not only by reductions in tumor cell adhesion, migration, intracellular glutathione (GSH levels and total antioxidant capability (T-AOC but also by increases in the apoptotic index, caspase3 activity, and reactive oxygen species (ROS. Furthermore, SIL treatment decreased the expression of the Notch1 intracellular domain (NICD, RBP-Jκ, and Hes1 proteins, upregulated the apoptosis pathway-related protein Bax, and downregulated Bcl2, survivin, and cyclin D1. Notch1 siRNA (in vitro or DAPT (a known Notch1 inhibitor, in vivo further enhanced the antitumor activity of SIL, and recombinant Jagged1 protein (a known Notch ligand in vitro attenuated the antitumor activity of SIL. Taken together, these data indicate that SIL is a potent inhibitor of HCC cell growth that targets the Notch signaling pathway and suggest that the inhibition of Notch signaling may be a novel therapeutic intervention for HCC.

  10. 3-dimensional Charge Collection Efficiency

    Kodak, Umut

    2013-01-01

    In this project, we designed a simulation program to create the efficiency map of a 3 dimensional rectangular detector. Efficiency is calculated by observing the collected charge at the output. Using this simulation program, one can observe the inefficient regions at not only on the surface of detector but at the depths of detector.

  11. Plumbagin exerts an immunosuppressive effect on human T-cell acute lymphoblastic leukemia MOLT-4 cells

    Bae, Kyoung Jun; Lee, Yura [Department of Biomedical Laboratory Science, Daejeon 34824 (Korea, Republic of); Kim, Soon Ae [Department of Pharmacology, School of Medicine, Daejeon 34824 (Korea, Republic of); Kim, Jiyeon, E-mail: yeon@eulji.ac.kr [Department of Biomedical Laboratory Science, Daejeon 34824 (Korea, Republic of)

    2016-04-22

    Of the hematological disorders typified by poor prognoses and survival rates, T-cell acute lymphoblastic leukemia (T-ALL) is one of the most commonly diagnosed. Despite the development of new therapeutic agents, the treatment options for this cancer remain limited. In this manuscript, we investigated the anti-proliferative effects of plumbagin, mediated by the activation of mitogen-activated protein kinase (MAPK) pathways, and inhibition of NF-κB signaling; the human T-ALL MOLT-4 cell line was used as our experimental system. Plumbagin is a natural, plant derived compound, which exerts an anti-proliferative activity against many types of human cancer. Our experiments confirm that plumbagin induces a caspase-dependent apoptosis of MOLT-4 cells, with no significant cytotoxicity seen for normal peripheral blood mononuclear cells (PBMCs). Plumbagin also inhibited LPS-induced phosphorylation of p65, and the transcription of NF-κB target genes. Our results now show that plumbagin is a potent inhibitor of the NF-κB signaling pathway, and suppressor of T-ALL cell proliferation. - Highlights: • Plumbagin induces caspase-dependent apoptosis in T-ALL MOLT-4 cells. • Plumbagin activates phosphorylation of stress-activated protein kinase (SAPK) JNK and p38. • Plumbagin inhibits LPS-mediated NF-κB signaling cascade. • Plumbagin inhibits LPS-mediated transcriptional activity of pro-inflammatory cytokines.

  12. Controlling human corneal stromal stem cell contraction to mediate rapid cell and matrix organization of real architecture for 3-dimensional tissue equivalents.

    Mukhey, Dev; Phillips, James B; Daniels, Julie T; Kureshi, Alvena K

    2018-02-01

    The architecture of the human corneal stroma consists of a highly organized extracellular matrix (ECM) interspersed with keratocytes. Their progenitor cells; corneal stromal stem cells (CSSC) are located at the periphery, in the limbal stroma. A highly organized corneal ECM is critical for effective transmission of light but this structure may be compromised during injury or disease, resulting in loss of vision. Re-creating normal organization in engineered tissue equivalents for transplantation often involves lengthy culture times that are inappropriate for clinical use or utilisation of synthetic substrates that bring complications such as corneal melting. CSSC have great therapeutic potential owing to their ability to reorganize a disorganized matrix, restoring transparency in scarred corneas. We examined CSSC contractile behavior to assess whether this property could be exploited to rapidly generate cell and ECM organization in Real Architecture For 3D Tissues (RAFT) tissue equivalents (TE) for transplantation. Free-floating collagen gels were characterized to assess contractile behavior of CSSC and establish optimum cell density and culture times. To mediate cell and collagen organization, tethered collagen gels seeded with CSSC were cultured and subsequently stabilized with the RAFT process. We demonstrated rapid creation of biomimetic RAFT TE with tunable structural properties. These displayed three distinct regions of varying degrees of cellular and collagen organization. Interestingly, increased organization coincided with a dramatic loss of PAX6 expression in CSSC, indicating rapid differentiation into keratocytes. The organized RAFT TE system could be a useful bioengineering tool to rapidly create an organized ECM while simultaneously controlling cell phenotype. For the first time, we have demonstrated that human CSSC exhibit the phenomenon of cellular self-alignment in tethered collagen gels. We found this mediated rapid co-alignment of collagen fibrils

  13. Human multipotent adult progenitor cells are nonimmunogenic and exert potent immunomodulatory effects on alloreactive T-cell responses.

    Jacobs, Sandra A; Pinxteren, Jef; Roobrouck, Valerie D; Luyckx, Ariane; van't Hof, Wouter; Deans, Robert; Verfaillie, Catherine M; Waer, Mark; Billiau, An D; Van Gool, Stefaan W

    2013-01-01

    Multipotent adult progenitor cells (MAPCs) are bone marrow-derived nonhematopoietic stem cells with a broad differentiation potential and extensive expansion capacity. A comparative study between human mesenchymal stem cells (hMSCs) and human MAPCs (hMAPCs) has shown that hMAPCs have clearly distinct phenotypical and functional characteristics from hMSCs. In particular, hMAPCs express lower levels of MHC class I than hMSCs and cannot only differentiate into typical mesenchymal cell types but can also differentiate in vitro and in vivo into functional endothelial cells. The use of hMSCs as cellular immunomodulatory stem cell products gained much interest since their immunomodulatory capacities in vitro became evident over the last decade. Currently, the clinical grade stem cell product of hMAPCs is already used in clinical trials to prevent graft-versus-host disease (GVHD), as well as for the treatment of acute myocardial infarct, ischemic stroke, and Crohn's disease. Therefore, we studied the immune phenotype, immunogenicity, and immunosuppressive effect of hMAPCs in vitro. We demonstrated that hMAPCs are nonimmunogenic for T-cell proliferation and cytokine production. In addition, hMAPCs exert strong immunosuppressive effects on T-cell alloreactivity and on T-cell proliferation induced by mitogens and recall antigens. This immunomodulatory effect was not MHC restricted, which makes off-the-shelf use promising. The immunosuppressive effect of hMAPCs is partially mediated via soluble factors and dependent on indoleamine 2,3-dioxygenase (IDO) activity. At last, we isolated hMAPCs, the clinical grade stem cell product of hMAPCs, named MultiStem, and hMSCs from one single donor and observed that both the immunogenicity and the immunosuppressive capacities of all three stem cell products are comparable in vitro. In conclusion, hMAPCs have potent immunomodulatory properties in vitro and can serve as a valuable cell source for the clinical use of immunomodulatory cellular

  14. Superparamagnetic iron oxide nanoparticles exert different cytotoxic effects on cells grown in monolayer cell culture versus as multicellular spheroids

    Theumer, Anja; Gräfe, Christine; Bähring, Franziska [Department of Hematology and Oncology, Jena University Hospital, Erlanger Allee 101, 07747 Jena (Germany); Bergemann, Christian [Chemicell GmbH, Eresburgstrasse 22–23, 12103 Berlin (Germany); Hochhaus, Andreas [Department of Hematology and Oncology, Jena University Hospital, Erlanger Allee 101, 07747 Jena (Germany); Clement, Joachim H., E-mail: joachim.clement@med.uni-jena.de [Department of Hematology and Oncology, Jena University Hospital, Erlanger Allee 101, 07747 Jena (Germany)

    2015-04-15

    The aim of this study was to investigate the interaction of superparamagnetic iron oxide nanoparticles (SPION) with human blood–brain barrier-forming endothelial cells (HBMEC) in two-dimensional cell monolayers as well as in three-dimensional multicellular spheroids. The precise nanoparticle localisation and the influence of the NP on the cellular viability and the intracellular Akt signalling were studied in detail. Long-term effects of different polymer-coated nanoparticles (neutral fluidMAG-D, anionic fluidMAG-CMX and cationic fluidMAG-PEI) and the corresponding free polymers on cellular viability of HBMEC were investigated by real time cell analysis studies. Nanoparticles exert distinct effects on HBMEC depending on the nanoparticles' surface charge and concentration, duration of incubation and cellular context. The most severe effects were caused by PEI-coated nanoparticles. Concentrations above 25 µg/ml led to increased amounts of dead cells in monolayer culture as well as in multicellular spheroids. On the level of intracellular signalling, context-dependent differences were observed. Monolayer cultures responded on nanoparticle incubation with an increase in Akt phosphorylation whereas spheroids on the whole show a decreased Akt activity. This might be due to the differential penetration and distribution of PEI-coated nanoparticles.

  15. Mesenchymal Stromal Cell Secreted Sphingosine 1-Phosphate (S1P) Exerts a Stimulatory Effect on Skeletal Myoblast Proliferation

    Tani, Alessia; Anderloni, Giulia; Pierucci, Federica; Matteini, Francesca; Chellini, Flaminia; Zecchi Orlandini, Sandra; Meacci, Elisabetta

    2014-01-01

    Bone-marrow-derived mesenchymal stromal cells (MSCs) have the potential to significantly contribute to skeletal muscle healing through the secretion of paracrine factors that support proliferation and enhance participation of the endogenous muscle stem cells in the process of repair/regeneration. However, MSC-derived trophic molecules have been poorly characterized. The aim of this study was to investigate paracrine signaling effects of MSCs on skeletal myoblasts. It was found, using a biochemical and morphological approach that sphingosine 1-phosphate (S1P), a natural bioactive lipid exerting a broad range of muscle cell responses, is secreted by MSCs and represents an important factor by which these cells exert their stimulatory effects on C2C12 myoblast and satellite cell proliferation. Indeed, exposure to conditioned medium obtained from MSCs cultured in the presence of the selective sphingosine kinase inhibitor (iSK), blocked increased cell proliferation caused by the conditioned medium from untreated MSCs, and the addition of exogenous S1P in the conditioned medium from MSCs pre-treated with iSK further increased myoblast proliferation. Finally, we also demonstrated that the myoblast response to MSC-secreted vascular endothelial growth factor (VEGF) involves the release of S1P from C2C12 cells. Our data may have important implications in the optimization of cell-based strategies to promote skeletal muscle regeneration. PMID:25264785

  16. Exerting Capacity.

    Leger, J Michael; Phillips, Carolyn A

    2017-05-01

    Patient safety has been at the forefront of nursing research since the release of the Institute of Medicine's report estimating the number of preventable adverse events in hospital settings; yet no research to date has incorporated the perspectives of bedside nurses using classical grounded theory (CGT) methodology. This CGT study explored the perceptions of bedside registered nurses regarding patient safety in adult acute care hospitals. Data analysis used three techniques unique to CGT-the constant comparative method, coding, and memoing-to explore the values, realities, and beliefs of bedside nurses about patient safety. The analysis resulted in a substantive theory, Exerting Capacity, which explained how bedside nurses balance the demands of keeping their patients safe. Exerting Capacity has implications for health care organization leaders, nursing leaders, and bedside nurses; it also has indications for future research into the concept of patient safety.

  17. Isometric Thumb Exertion Induces B Cell and T Cell Lymphocytosis in Trained and Untrained Males: Physical Aptitude Determines Response Profiles

    Adam Michael Szlezak

    2016-01-01

    Full Text Available Purpose: The present study examined the effect of low-dose thumb exertion on lymphocyte subpopulation trafficking. The potential role of blood lactate in mediating lymphocyte redistribution was also investigated. Methods: 27 male participants (18 weightlifting-trained; 9 untrained were separated into 3 groups of 9 (Weightlifting and Untrained Experimental: WLEXP, UTEXP; Weightlifting Placebo: WLPLA. WLEXP and UTEXP performed 4x60 second isometric thumb intervals separated by 60 second rest intervals in a single-blinded placebo-controlled study.  Participants were assessed over a 60 minute post-intervention recovery period for pain, blood lactate and lymphocyte subpopulation counts. Results: WLPLA did not change for any measured variable (p>0.05. The two experimentalgroups increased significantly (p0.05. No differences in cell count were seen for CD56+/CD16+ lymphocytes across time for any group (p>0.05. UTEXP showed an early significant increase (20 min post-intervention in CD4+CD3+ (20.78%, p0.05. Conversely, WLEXP group showed no early increase followed by a delayed increase in cell count evident at the final time-point; CD4+CD3+ (19.06%, p<0.01, CD8+CD3+ (11.46%, p=0.033 and CD19+ (28.87%, p<0.01. Blood lactate was not correlated with lymphocyte counts. Conclusions: Physical aptitude and not cellular energy demand influences the lymphocyte response to resistance-exercise. Keywords: B-Lymphocytes; Exercise; Lactic Acid; Lymphocytosis; Resistance Training; T-Lymphocytes

  18. Ganoderma lucidum exerts anti-tumor effects on ovarian cancer cells and enhances their sensitivity to cisplatin.

    Zhao, Sufen; Ye, Gang; Fu, Guodong; Cheng, Jian-Xin; Yang, Burton B; Peng, Chun

    2011-05-01

    Ganoderma lucidum is a herbal mushroom known to have many health benefits, including the inhibition of tumor cell growth. However, the effect of Ganoderma lucidum on epithelial ovarian cancer (EOC), the most fatal gynecological malignancy, has not yet been reported. In this study, we determined whether Ganoderma lucidum regulates EOC cell activity. Using several cell lines derived from EOC, we found that Ganoderma lucidum strongly decreased cell numbers in a dose-dependent manner. Ganoderma lucidum also inhibited colony formation, cell migration and spheroid formation. In particular, Ganoderma lucidum was effective in inhibiting cell growth in both chemosensitive and chemoresistant cells and the treatment with Ganoderma lucidum significantly enhanced the effect of cisplatin on EOC cells. Furthermore, Ganoderma lucidum induced cell cycle arrest at the G2/M phase and also induced apoptosis by activating caspase 3. Finally, Ganoderma lucidum increased p53 but inhibited Akt expression. Taken together, these findings suggest that Ganoderma lucidum exerts multiple anti-tumor effects on ovarian cancer cells and can enhance the sensitivity of EOC cells to cisplatin.

  19. Analysis of radiation pressure force exerted on a biological cell induced by high-order Bessel beams using Debye series

    Li, Renxian; Ren, Kuan Fang; Han, Xiang'e; Wu, Zhensen; Guo, Lixin; Gong, Shuxi

    2013-01-01

    Debye series expansion (DSE) is employed to the analysis of radiation pressure force (RPF) exerted on biological cells induced by high-order Bessel beams (BB). The beam shape coefficients (BSCs) for high-order Bessel beams are calculated using analytical expressions obtained by the integral localized approximation (ILA). Different types of cells, including a real Chinese Hamster Ovary (CHO) cell and a lymphocyte which are respectively modeled by a coated and five-layered sphere, are considered. The RPF induced by high-order Bessel beams is compared with that by Gaussian beams and zeroth-order Bessel beams, and the effect of different scattering processes on RPF is studied. Numerical calculations show that high-order Bessel beams with zero central intensity can also transversely trap particle in the beam center, and some scattering processes can provide longitudinal pulling force. -- Highlights: ► BSCs for high-order Bessel beam (HOBB) is derived using ILA. ► DSE is employed to study the RPF induced by HOBB exerted on multilayered cells. ► RPF is decided by radius relative to the interval of peaks in intensity profile. ► HOBB can also transversely trap high-index particle in the vicinity of beam axis. ► RPF for some scattering processes can longitudinally pull particles back

  20. Enavatuzumab, a Humanized Anti-TWEAK Receptor Monoclonal Antibody, Exerts Antitumor Activity through Attracting and Activating Innate Immune Effector Cells

    Shiming Ye

    2017-01-01

    Full Text Available Enavatuzumab is a humanized IgG1 anti-TWEAK receptor monoclonal antibody that was evaluated in a phase I clinical study for the treatment of solid malignancies. The current study was to determine whether and how myeloid effector cells were involved in postulated mechanisms for its potent antitumor activity in xenograft models. The initial evidence for a role of effector cells was obtained in a subset of tumor xenograft mouse models whose response to enavatuzumab relied on the binding of Fc of the antibody to Fcγ receptor. The involvement of effector cells was further confirmed by immunohistochemistry, which revealed strong infiltration of CD45+ effector cells into tumor xenografts in responding models, but minimal infiltration in nonresponders. Consistent with the xenograft studies, human effector cells preferentially migrated toward in vivo-responsive tumor cells treated by enavatuzumab in vitro, with the majority of migratory cells being monocytes. Conditioned media from enavatuzumab-treated tumor cells contained elevated levels of chemokines, which might be responsible for enavatuzumab-triggered effector cell migration. These preclinical studies demonstrate that enavatuzumab can exert its potent antitumor activity by actively recruiting and activating myeloid effectors to kill tumor cells. Enavatuzumab-induced chemokines warrant further evaluation in clinical studies as potential biomarkers for such activity.

  1. Tlx3 exerts context-dependent transcriptional regulation and promotes neuronal differentiation from embryonic stem cells

    Kondo, Takako; Sheets, Patrick L.; Zopf, David A.; Aloor, Heather L.; Cummins, Theodore R.; Chan, Rebecca J.; Hashino, Eri

    2008-01-01

    The T cell leukemia 3 (Tlx3) gene has been implicated in specification of glutamatergic sensory neurons in the spinal cord. In cranial sensory ganglia, Tlx3 is highly expressed in differentiating neurons during early embryogenesis. To study a role of Tlx3 during neural differentiation, mouse embryonic stem (ES) cells were transfected with a Tlx3 expression vector. ES cells stably expressing Tlx3 were grown in the presence or absence of a neural induction medium. In undifferentiated ES cells, ...

  2. Aspirin exerts high anti-cancer activity in PIK3CA-mutant colon cancer cells.

    Gu, Mancang; Nishihara, Reiko; Chen, Yang; Li, Wanwan; Shi, Yan; Masugi, Yohei; Hamada, Tsuyoshi; Kosumi, Keisuke; Liu, Li; da Silva, Annacarolina; Nowak, Jonathan A; Twombly, Tyler; Du, Chunxia; Koh, Hideo; Li, Wenbin; Meyerhardt, Jeffrey A; Wolpin, Brian M; Giannakis, Marios; Aguirre, Andrew J; Bass, Adam J; Drew, David A; Chan, Andrew T; Fuchs, Charles S; Qian, Zhi Rong; Ogino, Shuji

    2017-10-20

    Evidence suggests that nonsteroidal anti-inflammatory drug aspirin (acetylsalicylic acid) may improve patient survival in PIK3CA -mutant colorectal carcinoma, but not in PIK3CA -wild-type carcinoma. However, whether aspirin directly influences the viability of PIK3CA -mutant colon cancer cells is poorly understood. We conducted in vitro experiments to test our hypothesis that the anti-proliferative activity of aspirin might be stronger for PIK3CA -mutant colon cancer cells than for PIK3CA -wild-type colon cancer cells. We measured the anti-proliferative effect of aspirin at physiologic concentrations in seven PIK3CA -mutant and six PIK3CA -wild-type human colon cancer cell lines. After exposure to aspirin, the apoptotic index and cell cycle phase of colon cancer cells were assessed. In addition, the effect of aspirin was examined in parental SW48 cells and SW48 cell clones with individual knock-in PIK3CA mutations of either c.3140A>G (p.H1047R) or c.1633G>A (p.E545K). Aspirin induced greater dose-dependent loss of cell viability in PIK3CA -mutant cells than in PIK3CA -wild-type cells after treatment for 48 and 72 hours. Aspirin treatment also led to higher proportions of apoptotic cells and G0/G1 phase arrest in PIK3CA -mutant cells than in PIK3CA -wild-type cells. Aspirin treatment of isogenic SW48 cells carrying a PIK3CA mutation, either c.3140A>G (p.H1047R) or c.1633G>A (p. E545K), resulted in a more significant loss of cell viability compared to wild-type controls. Our findings indicate that aspirin causes cell cycle arrest, induces apoptosis, and leads to loss of cell viability more profoundly in PIK3CA -mutated colon cancer cells than in PIK3CA -wild-type colon cancer cells. These findings support the use of aspirin to treat patients with PIK3CA -mutant colon cancer.

  3. Semi-synthetic salinomycin analogs exert cytotoxic activity against human colorectal cancer stem cells.

    Klose, Johannes; Kattner, Sarah; Borgström, Björn; Volz, Claudia; Schmidt, Thomas; Schneider, Martin; Oredsson, Stina; Strand, Daniel; Ulrich, Alexis

    2018-01-01

    Salinomycin, a polyether antibiotic, is a well-known inhibitor of human cancer stem cells. Chemical modification of the allylic C20 hydroxyl of salinomycin has enabled access to synthetic analogs that display increased cytotoxic activity compared to the native structure. The aim of this study was to investigate the activity of a cohort of C20-O-acyl analogs of salinomycin on human colorectal cancer cell lines in vitro. Two human colorectal cancer cell lines (SW480 and SW620) were exposed to three C20-O-acylated analogs and salinomycin. The impact of salinomycin and its analogs on tumor cell number, migration, cell death, and cancer stem cell specifity was analyzed. Exposure of human colorectal cancer cells to the C20-O-acylated analogs of salinomycin resulted in reduced tumor cell number and impaired tumor cell migration at lower concentrations than salinomycin. When used at higher (micromolar) concentrations, these effects were accompanied by induction of apoptotic cell death. Salinomycin analogs further expose improved activity against cancer stem cells compared to salinomycin. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. NBPF1, a tumor suppressor candidate in neuroblastoma, exerts growth inhibitory effects by inducing a G1 cell cycle arrest

    Andries, Vanessa; Vandepoele, Karl; Staes, Katrien; Berx, Geert; Bogaert, Pieter; Van Isterdael, Gert; Ginneberge, Daisy; Parthoens, Eef; Vandenbussche, Jonathan; Gevaert, Kris; Roy, Frans van

    2015-01-01

    NBPF1 (Neuroblastoma Breakpoint Family, member 1) was originally identified in a neuroblastoma patient on the basis of its disruption by a chromosomal translocation t(1;17)(p36.2;q11.2). Considering this genetic defect and the frequent genomic alterations of the NBPF1 locus in several cancer types, we hypothesized that NBPF1 is a tumor suppressor. Decreased expression of NBPF1 in neuroblastoma cell lines with loss of 1p36 heterozygosity and the marked decrease of anchorage-independent clonal growth of DLD1 colorectal carcinoma cells with induced NBPF1 expression further suggest that NBPF1 functions as tumor suppressor. However, little is known about the mechanisms involved. Expression of NBPF was analyzed in human skin and human cervix by immunohistochemistry. The effects of NBPF1 on the cell cycle were evaluated by flow cytometry. We investigated by real-time quantitative RT-PCR the expression profile of a panel of genes important in cell cycle regulation. Protein levels of CDKN1A-encoded p21 CIP1/WAF1 were determined by western blotting and the importance of p53 was shown by immunofluorescence and by a loss-of-function approach. LC-MS/MS analysis was used to investigate the proteome of DLD1 colon cancer cells with induced NBPF1 expression. Possible biological interactions between the differentially regulated proteins were investigated with the Ingenuity Pathway Analysis tool. We show that NBPF is expressed in the non-proliferative suprabasal layers of squamous stratified epithelia of human skin and cervix. Forced expression of NBPF1 in HEK293T cells resulted in a G1 cell cycle arrest that was accompanied by upregulation of the cyclin-dependent kinase inhibitor p21 CIP1/WAF1 in a p53-dependent manner. Additionally, forced expression of NBPF1 in two p53-mutant neuroblastoma cell lines also resulted in a G1 cell cycle arrest and CDKN1A upregulation. However, CDKN1A upregulation by NBPF1 was not observed in the DLD1 cells, which demonstrates that NBPF1 exerts cell

  5. NKT Cell Subsets Can Exert Opposing Effects in Autoimmunity, Tumor Surveillance and Inflammation

    Viale, Rachael; Ware, Randle; Maricic, Igor; Chaturvedi, Varun; Kumar, Vipin

    2014-01-01

    The innate-like natural killer T (NKT) cells are essential regulators of immunity. These cells comprise at least two distinct subsets and recognize different lipid antigens presented by the MHC class I like molecules CD1d. The CD1d-dependent recognition pathway of NKT cells is highly conserved from mouse to humans. While most type I NKT cells can recognize αGalCer and express a semi-invariant T cell receptor (TCR), a major population of type II NKT cells reactive to sulfatide utilizes an oligoclonal TCR. Furthermore TCR recognition features of NKT subsets are also distinctive with almost parallel as opposed to perpendicular footprints on the CD1d molecules for the type I and type II NKT cells respectively. Here we present a view based upon the recent studies in different clinical and experimental settings that while type I NKT cells are more often pathogenic, they may also be regulatory. On the other hand, sulfatide-reactive type II NKT cells mostly play an inhibitory role in the control of autoimmune and inflammatory diseases. Since the activity and cytokine secretion profiles of NKT cell subsets can be modulated differently by lipid ligands or their analogs, novel immunotherapeutic strategies are being developed for their differential activation for potential intervention in inflammatory diseases. PMID:25288922

  6. Anti-Allergic Drugs Tranilast and Ketotifen Dose-Dependently Exert Mast Cell-Stabilizing Properties

    Asuka Baba

    2016-01-01

    Full Text Available Background: Anti-allergic drugs, such as tranilast and ketotifen, inhibit the release of chemokines from mast cells. However, we know little about their direct effects on the exocytotic process of mast cells. Since exocytosis in mast cells can be monitored electrophysiologically by changes in the whole-cell membrane capacitance (Cm, the absence of such changes by these drugs indicates their mast cell-stabilizing properties. Methods: Employing the standard patch-clamp whole-cell recording technique in rat peritoneal mast cells, we examined the effects of tranilast and ketotifen on the Cm during exocytosis. Using confocal imaging of a water-soluble fluorescent dye, lucifer yellow, we also examined their effects on the deformation of the plasma membrane. Results: Relatively lower concentrations of tranilast (100, 250 µM and ketotifen (1, 10 µM did not significantly affect the GTP-γ-S-induced increase in the Cm. However, higher concentrations of tranilast (500 µM, 1 mM and ketotifen (50, 100 µM almost totally suppressed the increase in the Cm, and washed out the trapping of the dye on the surface of the mast cells. Compared to tranilast, ketotifen required much lower doses to similarly inhibit the degranulation of mast cells or the increase in the Cm. Conclusions: This study provides electrophysiological evidence for the first time that tranilast and ketotifen dose-dependently inhibit the process of exocytosis, and that ketotifen is more potent than tranilast in stabilizing mast cells. The mast cell-stabilizing properties of these drugs may be attributed to their ability to counteract the plasma membrane deformation in degranulating mast cells.

  7. Ultrahigh Resolution 3-Dimensional Imaging, Phase I

    National Aeronautics and Space Administration — Southwest Sciences proposes to develop innovative instrumentation for the rapid, 3-dimensional imaging of biological tissues with cellular resolution. Our approach...

  8. Osteogenic potential of human adipose-derived stromal cells on 3-dimensional mesoporous TiO{sub 2} coating with magnesium impregnation

    Cecchinato, Francesca, E-mail: francesca.cecchinato@mah.se [Department of Prosthodontics, Faculty of Odontology, Malmö University, Malmö (Sweden); Karlsson, Johan [Department of Chemical and Biological Engineering, Applied Surface Chemistry, Chalmers University of Technology, Gothenburg (Sweden); Ferroni, Letizia; Gardin, Chiara [Department of Histology, Microbiology, and Medical Biotechnologies, University of Padova, Padova (Italy); Galli, Silvia; Wennerberg, Ann [Department of Prosthodontics, Faculty of Odontology, Malmö University, Malmö (Sweden); Zavan, Barbara [Department of Histology, Microbiology, and Medical Biotechnologies, University of Padova, Padova (Italy); Andersson, Martin [Department of Chemical and Biological Engineering, Applied Surface Chemistry, Chalmers University of Technology, Gothenburg (Sweden); Jimbo, Ryo [Department of Prosthodontics, Faculty of Odontology, Malmö University, Malmö (Sweden); Department of Applied Prosthodontics, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki (Japan)

    2015-07-01

    The aim of this study was to evaluate the osteogenic response of human adipose-derived stromal cells (ADScs) to mesoporous titania (TiO{sub 2}) coatings produced with evaporation-induced self-assembly method (EISA) and loaded with magnesium. Our emphasis with the magnesium release functionality was to modulate progenitor cell osteogenic differentiation under standard culture conditions. Osteogenic properties of the coatings were assessed for stromal cells by means of scanning electron microscopy (SEM) imaging, colorimetric mitochondrial viability assay (MTT), colorimetric alkaline phosphates activity (ALP) assay and real time RT-polymerase chain reaction (PCR). Using atomic force microscopy (AFM) it was shown that the surface expansion area (S{sub dr}) was strongly enhanced by the presence of magnesium. From MTT results it was shown that ADSc viability was significantly increased on mesoporous surfaces compared to the non-porous one at a longer cell culture time. However, no differences were observed between the magnesium impregnated and non-impregnated surfaces. The alkaline phosphatase activity confirmed that ADSc started to differentiate into the osteogenic phenotype after 2 weeks of culturing. The gene expression profile at 2 weeks of cell growth showed that such coatings were capable to incorporate specific osteogenic markers inside their interconnected nano-pores and, at 3 weeks, ADSc differentiated into osteoblasts. Interestingly, magnesium significantly promoted the osteopontin gene expression, which is an essential gene for the early biomaterial–cell osteogenic interaction. - Highlights: • The magnesium loading presents a transitory effect on mesoporous TiO{sub 2} surface topography • The mesoporous structure promotes cellular attachment and spreading • The mesoporous structure activates osteogenesis of mesenchymal stem cells in absence of osteogenic promoters • The physical adsorbed magnesium is suggested to be involved in the expression of

  9. Osteogenic potential of human adipose-derived stromal cells on 3-dimensional mesoporous TiO2 coating with magnesium impregnation

    Cecchinato, Francesca; Karlsson, Johan; Ferroni, Letizia; Gardin, Chiara; Galli, Silvia; Wennerberg, Ann; Zavan, Barbara; Andersson, Martin; Jimbo, Ryo

    2015-01-01

    The aim of this study was to evaluate the osteogenic response of human adipose-derived stromal cells (ADScs) to mesoporous titania (TiO 2 ) coatings produced with evaporation-induced self-assembly method (EISA) and loaded with magnesium. Our emphasis with the magnesium release functionality was to modulate progenitor cell osteogenic differentiation under standard culture conditions. Osteogenic properties of the coatings were assessed for stromal cells by means of scanning electron microscopy (SEM) imaging, colorimetric mitochondrial viability assay (MTT), colorimetric alkaline phosphates activity (ALP) assay and real time RT-polymerase chain reaction (PCR). Using atomic force microscopy (AFM) it was shown that the surface expansion area (S dr ) was strongly enhanced by the presence of magnesium. From MTT results it was shown that ADSc viability was significantly increased on mesoporous surfaces compared to the non-porous one at a longer cell culture time. However, no differences were observed between the magnesium impregnated and non-impregnated surfaces. The alkaline phosphatase activity confirmed that ADSc started to differentiate into the osteogenic phenotype after 2 weeks of culturing. The gene expression profile at 2 weeks of cell growth showed that such coatings were capable to incorporate specific osteogenic markers inside their interconnected nano-pores and, at 3 weeks, ADSc differentiated into osteoblasts. Interestingly, magnesium significantly promoted the osteopontin gene expression, which is an essential gene for the early biomaterial–cell osteogenic interaction. - Highlights: • The magnesium loading presents a transitory effect on mesoporous TiO 2 surface topography • The mesoporous structure promotes cellular attachment and spreading • The mesoporous structure activates osteogenesis of mesenchymal stem cells in absence of osteogenic promoters • The physical adsorbed magnesium is suggested to be involved in the expression of osteopontin

  10. Stem cells can form gap junctions with cardiac myocytes and exert pro-arrhythmic effects

    Nicoline Willemijn Smit

    2014-10-01

    Full Text Available Stem cell therapy has been suggested to be a promising option for regeneration of injured myocardium, for example following a myocardial infarction. For clinical use cell-based therapies have to be safe and applicable and are aimed to renovate the architecture of the heart. Yet for functional and coordinated activity synchronized with the host myocardium stem cells have to be capable of forming electrical connections with resident cardiomyocytes. In this paper we discuss whether stem cells are capable of establishing functional electrotonic connections with cardiomyocytes and whether these may generate a risk for arrhythmias. Application of stem cells in the clinical setting with outcomes concerning arrhythmogenic safety and future perspectives will also briefly be touched upon.

  11. Supraphysiological Doses of Performance Enhancing Anabolic-Androgenic Steroids Exert Direct Toxic Effects on Neuron-like Cells

    John Robert Basile

    2013-05-01

    Full Text Available Anabolic-androgenic steroids (AAS are lipophilic hormones often taken in excessive quantities by athletes and bodybuilders to enhance performance and increase muscle mass. AAS exert well known toxic effects on specific cell and tissue types and organ systems. The attention that androgen abuse has received lately should be used as an opportunity to educate both athletes and the general population regarding their adverse effects. Among numerous commercially available steroid hormones, very few have been specifically tested for direct neurotoxicity. We evaluated the effects of supraphysiological doses of methandienone and 17-α-methyltestosterone on sympathetic-like neuron cells. Vitality and apoptotic effects were analyzed, and immunofluorescence staining and western blot performed. In this study, we demonstrate that exposure of supraphysiological doses of methandienone and 17-α-methyltestosterone are toxic to the neuron-like differentiated pheochromocytoma cell line PC12, as confirmed by toxicity on neurite networks responding to nerve growth factor and the modulation of the survival and apoptosis-related proteins ERK, caspase-3, poly (ADP-ribose polymerase and heat-shock protein 90. We observe, in contrast to some previous reports but in accordance with others, expression of the androgen receptor (AR in neuron-like cells, which when inhibited mitigated the toxic effects of AAS tested, suggesting that the AR could be binding these steroid hormones to induce genomic effects. We also note elevated transcription of neuritin in treated cells, a neurotropic factor likely expressed in an attempt to resist neurotoxicity. Taken together, these results demonstrate that supraphysiological exposure to the AAS methandienone and 17-α-methyltestosterone exert neurotoxic effects by an increase in the activity of the intrinsic apoptotic pathway and alterations in neurite networks.

  12. Bovine lactoferrin and lactoferricin exert antitumor activities on human colorectal cancer cells (HT-29) by activating various signaling pathways.

    Jiang, Rulan; Lönnerdal, Bo

    2017-02-01

    Lactoferrin (Lf) is an iron-binding glycoprotein that is present at high concentrations in milk. Bovine lactoferricin (LfcinB) is a peptide fragment generated by pepsin proteolysis of bovine lactoferrin (bLf). LfcinB consists of amino acid residues 17-41 proximal to the N-terminus of bLf and a disulfide bond between residues 19 and 36, forming a loop. Both bLf and LfcinB have been demonstrated to have antitumor activities. Colorectal cancer is the second most common cause of cancer death in developed countries. We hypothesized that bLf and LfcinB exert antitumor activities on colon cancer cells (HT-29) by triggering various signaling pathways. bLf and LfcinB significantly induced apoptosis in HT-29 cells but not in normal human intestinal epithelial cells, as revealed by the ApoTox-Glo Triplex Assay. The LIVE/DEAD cell viability assay showed that both bLf and LfcinB reduced the viability of HT-29 cells. Transcriptome analysis indicated that bLf, cyclic LfcinB, and linear LfcinB exerted antitumor activities by differentially activating diverse signaling pathways, including p53, apoptosis, and angiopoietin signaling. Immunoblotting results confirmed that both bLf and LfcinBs increased expression of caspase-8, p53, and p21, critical proteins in tumor suppression. These results provide valuable information regarding bLf and LfcinB for potential clinical applications in colon cancer therapy.

  13. Primula auriculata Extracts Exert Cytotoxic and Apoptotic Effects against HT-29 Human Colon Adenocarcinoma Cells.

    Behzad, Sahar; Ebrahim, Karim; Mosaddegh, Mahmoud; Haeri, Ali

    2016-01-01

    Primula auriculata (Tootia) is one of the most important local medicinal plants in Hamedan district, Iran. To investigate cytotoxicity and apoptosis induction of crude methanolic extract and different fraction of it, we compared several methods on HT-29 human colon Adenocarcinoma cells. Cancer cell proliferation was measured by 3-(4, 5‑dimethylthiazolyl)2, 5‑diphenyl‑tetrazolium bromide (MTT) assay and apoptosis induction was analyzed by fluorescence microscopy (acridin orange/ethidium bromide, annexin V/propidium iodide staining, TUNEL assay and Caspase-3 activity assay). Crude methanolic extract (CM) inhibited the growth of malignant cells in a dose-dependent manner. Among solvent fractions, the dichloromethane fraction (CF) was found to be the most toxic compared to other fractions. With double staining methods, high percentage of 40 µg/mL of (CM) and (CF) treated cells exhibited typical characteristics of apoptotic cells. Apoptosis induction was also revealed by apoptotic fragmentation of nuclear DNA and activation of caspas-3 in treated cells. These findings indicate that crude methanolic extract and dichloromethan fraction of P.auriculata induced apoptosis and inhibited proliferation in colon cancer cells and could be used as a source for new lead structures in drug design to combat colon cancer.

  14. Effects of 3-dimensional culture conditions (collagen-chitosan nano-scaffolds) on maturation of dendritic cells and their capacity to interact with T-lymphocytes.

    Daneshmandi, Saeed; Dibazar, Shaghayegh Pishkhan; Fateh, Shirin

    2016-01-01

    In the body, there is a natural three-dimensional (3D) microenvironment in which immune cells, including dendritic cells (DC), play their functions. This study evaluated the impact of using collagen-chitosan 3D nano-scaffolds in comparisons to routine 2D culture plates on DC phenotype and functions. Bone marrow-derived DC were cultured on scaffolds and plates and then stimulated with lipopolysaccharide (LPS) or chitosan-based nanoparticles (NP) for 24 h. Thereafter, DC viability, expression of maturation markers and levels of cytokines secretion were evaluated. In another set of studies, the DC were co-cultured with allogenic T-lymphocytes in both the 2D and 3D systems and effects on DC-induction of T-lymphocyte proliferation and cytokine release were analyzed. The results indicated that CD40, CD86 and MHC II marker expression and interleukin (IL)-12, IL-6 and tumor necrosis factor (TNF)-α secretion by DC were enhanced in 3D cultures in comparison to by cells maintained in the 2D states. The data also showed that DNA/chitosan NP activated DC more than LPS in the 3D system. T-Lymphocyte proliferation was induced to a greater extent by DNA/NP-treated DC when both cell types were maintained on the scaffolds. Interestingly, while DC induction of T-lymphocyte interferon (IFN)-γ and IL-4 release was enhanced in the 3D system (relative to controls), there was a suppression of transforming growth factor (TGF)-β production; effects on IL-10 secretion were variable. The results here suggested that collagen-chitosan scaffolds could provide a pro-inflammatory and activator environment to perform studies to analyze effects of exogenous agents on the induction of DC maturation, NP uptake and/or cytokines release, as well as for the ability of these cells to potentially interact with other immune system cells in vitro.

  15. Bim and Mcl-1 exert key roles in regulating JAK2V617F cell survival

    Rubert, Joëlle; Qian, Zhiyan; Andraos, Rita; Guthy, Daniel A; Radimerski, Thomas

    2011-01-01

    The JAK2 V617F mutation plays a major role in the pathogenesis of myeloproliferative neoplasms and is found in the vast majority of patients suffering from polycythemia vera and in roughly every second patient suffering from essential thrombocythemia or from primary myelofibrosis. The V617F mutation is thought to provide hematopoietic stem cells and myeloid progenitors with a survival and proliferation advantage. It has previously been shown that activated JAK2 promotes cell survival by upregulating the anti-apoptotic STAT5 target gene Bcl-xL. In this study, we have investigated the role of additional apoptotic players, the pro-apoptotic protein Bim as well as the anti-apoptotic protein Mcl-1. Pharmacological inhibition of JAK2/STAT5 signaling in JAK2 V617F mutant SET-2 and MB-02 cells was used to study effects on signaling, cell proliferation and apoptosis by Western blot analysis, WST-1 proliferation assays and flow cytometry. Cells were transfected with siRNA oligos to deplete candidate pro- and anti-apoptotic proteins. Co-immunoprecipitation assays were performed to assess the impact of JAK2 inhibition on complexes of pro- and anti-apoptotic proteins. Treatment of JAK2 V617F mutant cell lines with a JAK2 inhibitor was found to trigger Bim activation. Furthermore, Bim depletion by RNAi suppressed JAK2 inhibitor-induced cell death. Bim activation following JAK2 inhibition led to enhanced sequestration of Mcl-1, besides Bcl-xL. Importantly, Mcl-1 depletion by RNAi was sufficient to compromise JAK2 V617F mutant cell viability and sensitized the cells to JAK2 inhibition. We conclude that Bim and Mcl-1 have key opposing roles in regulating JAK2 V617F cell survival and propose that inactivation of aberrant JAK2 signaling leads to changes in Bim complexes that trigger cell death. Thus, further preclinical evaluation of combinations of JAK2 inhibitors with Bcl-2 family antagonists that also tackle Mcl-1, besides Bcl-xL, is warranted to assess the therapeutic potential

  16. Androgens Exert a Cysticidal Effect upon Taenia crassiceps by Disrupting Flame Cell Morphology and Function

    Ambrosio, Javier R.; Valverde-Islas, Laura; Nava-Castro, Karen E.; Palacios- Arreola, M. Isabel; Ostoa-Saloma, Pedro; Reynoso-Ducoing, Olivia; Escobedo, Galileo; Ruíz-Rosado, Azucena; Dominguez-Ramírez, Lenin; Morales-Montor, Jorge

    2015-01-01

    The effects of testosterone (T4) and dihydrotestosterone (DHT) on the survival of the helminth cestode parasite Taenia crassiceps, as well as their effects on actin, tubulin and myosin expression and their assembly into the excretory system of flame cells are described in this paper. In vitro evaluations on parasite viability, flow cytometry, confocal microscopy, video-microscopy of live flame cells, and docking experiments of androgens interacting with actin, tubulin, and myosin were conducted. Our results show that T4 and DHT reduce T. crassiceps viability in a dose- and time-dependent fashion, reaching 90% of mortality at the highest dose used (40 ng/ml) and time exposed (10 days) in culture. Androgen treatment does not induce differences in the specific expression pattern of actin, tubulin, and myosin isoforms as compared with control parasites. Confocal microscopy demonstrated a strong disruption of the parasite tegument, with reduced assembly, shape, and motion of flame cells. Docking experiments show that androgens are capable of affecting parasite survival and flame cell morphology by directly interacting with actin, tubulin and myosin without altering their protein expression pattern. We show that both T4 and DHT are able to bind actin, tubulin, and myosin affecting their assembly and causing parasite intoxication due to impairment of flame cell function. Live flame cell video microscopy showing a reduced motion as well changes in the shape of flame cells are also shown. In summary, T4 and DHT directly act on T. crassiceps cysticerci through altering parasite survival as well as the assembly and function of flame cells. PMID:26076446

  17. Combination of gefitinib and DNA methylation inhibitor decitabine exerts synergistic anti-cancer activity in colon cancer cells.

    Yun-feng Lou

    Full Text Available Despite recent advances in the treatment of human colon cancer, the chemotherapy efficacy against colon cancer is still unsatisfactory. In the present study, effects of concomitant inhibition of the epidermal growth factor receptor (EGFR and DNA methyltransferase were examined in human colon cancer cells. We demonstrated that decitabine (a DNA methyltransferase inhibitor synergized with gefitinib (an EGFR inhibitor to reduce cell viability and colony formation in SW1116 and LOVO cells. However, the combination of the two compounds displayed minimal toxicity to NCM460 cells, a normal human colon mucosal epithelial cell line. The combination was also more effective at inhibiting the AKT/mTOR/S6 kinase pathway. In addition, the combination of decitabine with gefitinib markedly inhibited colon cancer cell migration. Furthermore, gefitinib synergistically enhanced decitabine-induced cytotoxicity was primarily due to apoptosis as shown by Annexin V labeling that was attenuated by z-VAD-fmk, a pan caspase inhibitor. Concomitantly, cell apoptosis resulting from the co-treatment of gefitinib and decitabine was accompanied by induction of BAX, cleaved caspase 3 and cleaved PARP, along with reduction of Bcl-2 compared to treatment with either drug alone. Interestingly, combined treatment with these two drugs increased the expression of XIAP-associated factor 1 (XAF1 which play an important role in cell apoptosis. Moreover, small interfering RNA (siRNA depletion of XAF1 significantly attenuated colon cancer cells apoptosis induced by the combination of the two drugs. Our findings suggested that gefitinib in combination with decitabine exerted enhanced cell apoptosis in colon cancer cells were involved in mitochondrial-mediated pathway and induction of XAF1 expression. In conclusion, based on the observations from our study, we suggested that the combined administration of these two drugs might be considered as a novel therapeutic regimen for treating colon

  18. Mast cells exert pro-inflammatory effects of relevance to the pathophyisology of tendinopathy.

    Behzad, Hayedeh; Sharma, Aishwariya; Mousavizadeh, Rouhollah; Lu, Alex; Scott, Alex

    2013-01-01

    We have previously found an increased mast cell density in tendon biopsies from patients with patellar tendinopathy compared to controls. This study examined the influence of mast cells on basic tenocyte functions, including production of the inflammatory mediator prostaglandin E2 (PGE2), extracellular matrix remodeling and matrix metalloproteinase (MMP) gene transcription, and collagen synthesis. Primary human tenocytes were stimulated with an established human mast cell line (HMC-1). Extracellular matrix remodeling was studied by culturing tenocytes in a three-dimensional collagen lattice. Survival/proliferation was assessed with the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium salt (MTS) assay. Levels of mRNA for COX-2, COL1A1, MMP1, and MMP7 were determined by quantitative real-time polymerase chain reaction (qPCR). Cox-2 protein level was assessed by Western blot analysis and type I procollagen was detected by immunofluorescent staining. PGE2 levels were determined using an enzyme-linked immunosorbent assay (ELISA). Mast cells stimulated tenocytes to produce increased levels of COX-2 and the pro-inflammatory mediator PGE2, which in turn decreased COL1A1 mRNA expression. Additionally, mast cells reduced the type I procollagen protein levels produced by tenocytes. Transforming growth factor beta 1 (TGF-β1) was responsible for the induction of Cox-2 and PGE2 by tenocytes. Mast cells increased MMP1 and MMP7 transcription and increased the contraction of a three-dimensional collagen lattice by tenocytes, a phenomenon which was blocked by a pan-MMP inhibitor (Batimastat). Our data demonstrate that mast cell-derived PGE2 reduces collagen synthesis and enhances expression and activities of MMPs in human tenocytes.

  19. Ethanol exerts dual effects on calcium homeostasis in CCK-8-stimulated mouse pancreatic acinar cells.

    Fernández-Sánchez, Marcela; del Castillo-Vaquero, Angel; Salido, Ginés M; González, Antonio

    2009-10-30

    A significant percentage of patients with pancreatitis often presents a history of excessive alcohol consumption. Nevertheless, the patho-physiological effect of ethanol on pancreatitis remains poorly understood. In the present study, we have investigated the early effects of acute ethanol exposure on CCK-8-evoked Ca2+ signals in mouse pancreatic acinar cells. Changes in [Ca2+]i and ROS production were analyzed employing fluorescence techniques after loading cells with fura-2 or CM-H2DCFDA, respectively. Ethanol, in the concentration range from 1 to 50 mM, evoked an oscillatory pattern in [Ca2+]i. In addition, ethanol evoked reactive oxygen species generation (ROS) production. Stimulation of cells with 1 nM or 20 pM CCK-8, respectively led to a transient change and oscillations in [Ca2+]i. In the presence of ethanol a transformation of 20 pM CCK-8-evoked physiological oscillations into a single transient increase in [Ca2+]i in the majority of cells was observed. Whereas, in response to 1 nM CCK-8, the total Ca2+ mobilization was significantly increased by ethanol pre-treatment. Preincubation of cells with 1 mM 4-MP, an inhibitor of alcohol dehydrogenase, or 10 microM of the antioxidant cinnamtannin B-1, reverted the effect of ethanol on total Ca2+ mobilization evoked by 1 nM CCK-8. Cinnamtannin B-1 blocked ethanol-evoked ROS production. ethanol may lead, either directly or through ROS generation, to an over stimulation of pancreatic acinar cells in response to CCK-8, resulting in a higher Ca2+ mobilization compared to normal conditions. The actions of ethanol on CCK-8-stimulation of cells create a situation potentially leading to Ca2+ overload, which is a common pathological precursor that mediates pancreatitis.

  20. Ethanol exerts dual effects on calcium homeostasis in CCK-8-stimulated mouse pancreatic acinar cells

    Salido Ginés M

    2009-10-01

    Full Text Available Abstract Background A significant percentage of patients with pancreatitis often presents a history of excessive alcohol consumption. Nevertheless, the patho-physiological effect of ethanol on pancreatitis remains poorly understood. In the present study, we have investigated the early effects of acute ethanol exposure on CCK-8-evoked Ca2+ signals in mouse pancreatic acinar cells. Changes in [Ca2+]i and ROS production were analyzed employing fluorescence techniques after loading cells with fura-2 or CM-H2DCFDA, respectively. Results Ethanol, in the concentration range from 1 to 50 mM, evoked an oscillatory pattern in [Ca2+]i. In addition, ethanol evoked reactive oxygen species generation (ROS production. Stimulation of cells with 1 nM or 20 pM CCK-8, respectively led to a transient change and oscillations in [Ca2+]i. In the presence of ethanol a transformation of 20 pM CCK-8-evoked physiological oscillations into a single transient increase in [Ca2+]i in the majority of cells was observed. Whereas, in response to 1 nM CCK-8, the total Ca2+ mobilization was significantly increased by ethanol pre-treatment. Preincubation of cells with 1 mM 4-MP, an inhibitor of alcohol dehydrogenase, or 10 μM of the antioxidant cinnamtannin B-1, reverted the effect of ethanol on total Ca2+ mobilization evoked by 1 nM CCK-8. Cinnamtannin B-1 blocked ethanol-evoked ROS production. Conclusion ethanol may lead, either directly or through ROS generation, to an over stimulation of pancreatic acinar cells in response to CCK-8, resulting in a higher Ca2+ mobilization compared to normal conditions. The actions of ethanol on CCK-8-stimulation of cells create a situation potentially leading to Ca2+ overload, which is a common pathological precursor that mediates pancreatitis.

  1. Binase Immobilized on Halloysite Nanotubes Exerts Enhanced Cytotoxicity toward Human Colon Adenocarcinoma Cells

    Vera Khodzhaeva

    2017-09-01

    Full Text Available Many ribonucleases (RNases are considered as promising tools for antitumor therapy because of their selective cytotoxicity toward cancer cells. Binase, the RNase from Bacillus pumilus, triggers apoptotic response in cancer cells expressing RAS oncogene which is mutated in a large percentage of prevalent and deadly malignancies including colorectal cancer. The specific antitumor effect of binase toward RAS-transformed cells is due to its direct binding of RAS protein and inhibition of downstream signaling. However, the delivery of proteins to the intestine is complicated by their degradation in the digestive tract and subsequent loss of therapeutic activity. Therefore, the search of new systems for effective delivery of therapeutic proteins is an actual task. This study is aimed to the investigation of antitumor effect of binase immobilized on natural halloysite nanotubes (HNTs. Here, we have developed the method of binase immobilization on HNTs and optimized the conditions for the enzyme loading and release (i; we have found the non-toxic concentration of pure HNTs which allows to distinguish HNTs- and binase-induced cytotoxic effects (ii; using dark-field and fluorescent microscopy we have proved the absorption of binase-loaded HNTs on the cell surface (iii and demonstrated that binase-halloysite nanoformulations possessed twice enhanced cytotoxicity toward tumor colon cells as compared to the cytotoxicity of binase itself (iv. The enhanced antitumor activity of biocompatible binase-HNTs complex confirms the advisability of its future development for clinical practice.

  2. PRGF exerts a cytoprotective role in zoledronic acid-treated oral cells.

    Anitua, Eduardo; Zalduendo, Mar; Troya, María; Orive, Gorka

    2016-04-01

    Bisphosphonates-related osteonecrosis of the jaw (BRONJ) is a common problem in patients undergoing long-term administration of highly potent nitrogen-containing bisphosphonates (N-BPs). This pathology occurs via bone and soft tissue mechanism. Zoledronic acid (ZA) is the most potent intravenous N-BP used to prevent bone loss in patients with bone dysfunction. The objective of this in vitro study was to evaluate the role of different ZA concentrations on the cells from human oral cavity, as well as the potential of plasma rich in growth factors (PRGF) to overcome the negative effects of this BP. Primary human gingival fibroblasts and primary human alveolar osteoblasts were used. Cell proliferation was evaluated by means of a fluorescence-based method. A colorimetric assay to detect DNA fragmentation undergoing apoptosis was used to determine cell death, and the expression of both NF-κB and pNF-κB were quantified by Western blot analysis. ZA had a cytotoxic effect on both human gingival fibroblasts and human alveolar osteoblasts. This BP inhibits cell proliferation, stimulates apoptosis, and induces inflammation. However, the addition of PRGF suppresses all these negative effects of the ZA. PRGF shows a cytoprotective role against the negative effects of ZA on primary oral cells. At present, there is no definitive treatment for bisphosphonates-related osteonecrosis of the jaw (BRONJ), being mainly palliatives. Our results revealed that PRGF has a cytoprotective role in cells exposed to zoledronic acid, thus providing a reliable adjunctive therapy for the treatment of BRONJ pathology.

  3. Common Effects on Follicular Thyroid Cancer Cells Exerted by Simulated Microgravity

    Svejgaard, Benjamin; Grimm, Daniela; Corydon, Thomas Juhl

    2015-01-01

    This study focuses on gravity-sensitive proteins of two human follicular cancer cell lines (ML-1; RO82-W-1), which were exposed to simulated microgravity (s-μg) on two different machines. Changes in protein cytoskeletal structure, growth patterns and protein expression in response to s-μg were...

  4. Mitochondrial uncoupler exerts a synthetic lethal effect against β-catenin mutant tumor cells.

    Shikata, Yuki; Kiga, Masaki; Futamura, Yushi; Aono, Harumi; Inoue, Hiroyuki; Kawada, Manabu; Osada, Hiroyuki; Imoto, Masaya

    2017-04-01

    The wingless/int-1 (Wnt) signal transduction pathway plays a central role in cell proliferation, survival, differentiation and apoptosis. When β-catenin: a component of the Wnt pathway, is mutated into an active form, cell growth signaling is hyperactive and drives oncogenesis. As β-catenin is mutated in a wide variety of tumors, including up to 10% of all sporadic colon carcinomas and 20% of hepatocellular carcinomas, it has been considered a promising target for therapeutic interventions. Therefore, we screened an in-house natural product library for compounds that exhibited synthetic lethality towards β-catenin mutations and isolated nonactin, an antibiotic mitochondrial uncoupler, as a hit compound. Nonactin, as well as other mitochondrial uncouplers, induced apoptosis selectively in β-catenin mutated tumor cells. Significant tumor regression was observed in the β-catenin mutant HCT 116 xenograft model, but not in the β-catenin wild type A375 xenograft model, in response to daily administration of nonactin in vivo. Furthermore, we found that expression of an active mutant form of β-catenin induced a decrease in the glycolysis rate. Taken together, our results demonstrate that tumor cells with mutated β-catenin depend on mitochondrial oxidative phosphorylation for survival. Therefore, they undergo apoptosis in response to mitochondrial dysfunction following the addition of mitochondrial uncouplers, such as nonactin. These results suggest that targeting mitochondria is a potential chemotherapeutic strategy for tumor cells that harbor β-catenin mutations. © 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

  5. ADAM13 function is required in the 3 dimensional context of the embryo during cranial neural crest cell migration in Xenopus laevis

    Cousin, Hélène; Abbruzzese, Genevieve; McCusker, Catherine; Alfandari, Dominique

    2012-01-01

    The cranial neural crest (CNC) is a population of cells that arises from the lateral part of the developing brain, migrates ventrally and coordinates the entire craniofacial development of vertebrates. Many molecules are involved in CNC migration including the transmembrane metalloproteases ADAM13 and 19. We have previously shown that these ADAMs cleave a number of extracellular proteins and modify the transcription of a number of genes, and that both of these activities are important for cell migration. Here we show that the knock down of ADAM13 inhibits CNC migration in vivo but not in vitro, indicating that ADAM13 function is required in the 3-dimentional context of the embryo. We further show that the migration of CNC that do not express ADAM13 and ADAM19 can be rescued in vivo by co-grafting wild type CNC. Furthermore, the migration of CNC lacking ADAM13 can be rescued by mechanically separating the CNC from the surrounding ectoderm and mesoderm. Finally, we show that ADAM13 function is autonomous to CNC tissue, as the migration of morphant CNC can only be rescued by ADAM13 expression in the CNC and not the surrounding tissues. Together our results suggest that ADAM13 changes CNC interaction with the extracellular environment and that this change is necessary for their migration in vivo. PMID:22683825

  6. Hsp40 gene therapy exerts therapeutic effects on polyglutamine disease mice via a non-cell autonomous mechanism.

    H Akiko Popiel

    Full Text Available The polyglutamine (polyQ diseases such as Huntington's disease (HD, are neurodegenerative diseases caused by proteins with an expanded polyQ stretch, which misfold and aggregate, and eventually accumulate as inclusion bodies within neurons. Molecules that inhibit polyQ protein misfolding/aggregation, such as Polyglutamine Binding Peptide 1 (QBP1 and molecular chaperones, have been shown to exert therapeutic effects in vivo by crossing of transgenic animals. Towards developing a therapy using these aggregation inhibitors, we here investigated the effect of viral vector-mediated gene therapy using QBP1 and molecular chaperones on polyQ disease model mice. We found that injection of adeno-associated virus type 5 (AAV5 expressing QBP1 or Hsp40 into the striatum both dramatically suppresses inclusion body formation in the HD mouse R6/2. AAV5-Hsp40 injection also ameliorated the motor impairment and extended the lifespan of R6/2 mice. Unexpectedly, we found even in virus non-infected cells that AAV5-Hsp40 appreciably suppresses inclusion body formation, suggesting a non-cell autonomous therapeutic effect. We further show that Hsp40 inhibits secretion of the polyQ protein from cultured cells, implying that it inhibits the recently suggested cell-cell transmission of the polyQ protein. Our results demonstrate for the first time the therapeutic effect of Hsp40 gene therapy on the neurological phenotypes of polyQ disease mice.

  7. A novel adipocytokine, chemerin exerts anti-inflammatory roles in human vascular endothelial cells

    Yamawaki, Hideyuki, E-mail: yamawaki@vmas.kitasato-u.ac.jp [Laboratory of Veterinary Pharmacology, School of Veterinary Medicine, Kitasato University, Aomori 034-8628 (Japan); Kameshima, Satoshi; Usui, Tatsuya; Okada, Muneyoshi; Hara, Yukio [Laboratory of Veterinary Pharmacology, School of Veterinary Medicine, Kitasato University, Aomori 034-8628 (Japan)

    2012-06-22

    Highlights: Black-Right-Pointing-Pointer Chemerin is a novel adipocytokine with almost unknown function in vasculature. Black-Right-Pointing-Pointer Chemerin activates Akt/eNOS/NO pathways in endothelial cells. Black-Right-Pointing-Pointer Chemerin inhibits TNF-{alpha}-induced monocyte adhesion to endothelial cells. Black-Right-Pointing-Pointer Chemerin inhibits TNF-induced VCAM-1 via suppressing NF-{kappa}B and p38 signal. Black-Right-Pointing-Pointer Chemerin is anti-inflammatory through producing NO in vascular endothelium. -- Abstract: Chemerin is a recently identified adipocytokine which plays a role on inflammation and adipocytes metabolism. However, its function in vasculature is largely unknown. We examined the effects of chemerin on vascular endothelial inflammatory states. Treatment of human umbilical vein endothelial cells with chemerin (300 ng/ml, 20 min) induced phosphorylation of Akt (Ser473) and endothelial nitric oxide (NO) synthase (eNOS) (Ser1177). Consistently, chemerin increased intracellular cyclic GMP content. Pretreatment with chemerin (1-300 ng/ml, 24 h) significantly inhibited phosphorylation of nuclear factor (NF)-{kappa}B p65 (Ser536) and p38 as well as vascular cell adhesion molecule (VCAM)-1 expression induced by tumor necrosis factor (TNF)-{alpha} (5 ng/ml, 20 min-6 h). Inhibitor of NF-{kappa}B or p38 significantly inhibited the TNF-{alpha}-induced VCAM-1 expression. Chemerin also inhibited TNF-{alpha}-induced VCAM-1 expression in rat isolated aorta. Moreover, chemerin significantly inhibited monocytes adhesion to TNF-{alpha}-stimulated endothelial cells. The inhibitory effect of chemerin on TNF-{alpha}-induced VCAM-1 was reversed by a NOS inhibitor. Conversely, an NO donor, sodium nitroprusside significantly inhibited TNF-{alpha}-induced VCAM-1. The present results for the first time demonstrate that chemerin plays anti-inflammatory roles by preventing TNF-{alpha}-induced VCAM-1 expression and monocytes adhesion in vascular

  8. Gentiana lutea exerts anti-atherosclerotic effects by preventing endothelial inflammation and smooth muscle cell migration.

    Kesavan, R; Chandel, S; Upadhyay, S; Bendre, R; Ganugula, R; Potunuru, U R; Giri, H; Sahu, G; Kumar, P Uday; Reddy, G Bhanuprakash; Joksic, G; Bera, A K; Dixit, Madhulika

    2016-04-01

    Studies suggest that Gentiana lutea (GL), and its component isovitexin, may exhibit anti-atherosclerotic properties. In this study we sought to investigate the protective mechanism of GL aqueous root extract and isovitexin on endothelial inflammation, smooth muscle cell migation, and on the onset and progression of atherosclerosis in streptozotocin (STZ)-induced diabetic rats. Our results show that both GL extract and isovitexin, block leukocyte adhesion and generation of reactive oxygen species in human umbilical vein endothelial cells (HUVECs) and rat aortic smooth muscle cells (RASMCs), following TNF-alpha and platelet derived growth factor-BB (PDGF-BB) challenges respectively. Both the extract and isovitexin blocked TNF-α induced expression of ICAM-1 and VCAM-1 in HUVECs. PDGF-BB induced migration of RASMCs and phospholipase C-γ activation, were also abrogated by GL extract and isovitexin. Fura-2 based ratiometric measurements demonstrated that, both the extact, and isovitexin, inhibit PDGF-BB mediated intracellular calcium rise in RASMCs. Supplementation of regular diet with 2% GL root powder for STZ rats, reduced total cholesterol in blood. Oil Red O staining demonstrated decreased lipid accumulation in aortic wall of diabetic animals upon treatment with GL. Medial thickness and deposition of collagen in the aortic segment of diabetic rats were also reduced upon supplementation. Immunohistochemistry demonstrated reduced expression of vascular cell adhesion molecule-1 (VCAM-1), inducible nitric oxide synthase (iNOS), and vascular endothelial cadherin (VE-cadherin) in aortic segments of diabetic rats following GL treatment. Thus, our results support that GL root extract/powder and isovitexin exhibit anti-atherosclerotic activities. Copyright © 2016 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University

  9. PRGF exerts more potent proliferative and anti-inflammatory effects than autologous serum on a cell culture inflammatory model.

    Anitua, E; Muruzabal, F; de la Fuente, M; Riestra, A; Merayo-Lloves, J; Orive, G

    2016-10-01

    Ocular graft versus host disease (oGVHD) is part of a systemic inflammatory disease that usually affects ocular surface tissues manifesting as a dry eye syndrome. Current treatments provide unsatisfactory results. Blood-derived products, like plasma rich in growth factors (PRGF) emerge as a potential therapy for this disease. The purpose of this study was to evaluate the tissue regeneration and anti-inflammatory capability of PRGF, an autologous platelet enriched plasma eye-drop, compared to autologous serum (AS) obtained from oGVHD patients on ocular surface cells cultured in a pro-inflammatory environment. PRGF and AS were obtained from four GVHD patients. Cell proliferation and inflammation markers, intercellular adhesion molecule-1 (ICAM-1) and cyclooxygenase-2 (COX-2), were measured in corneal and conjunctival fibroblastic cells cultured under pro-inflammatory conditions and after treatment with PRGF or AS eye drops. Moreover, cell proliferation increased after treatment with PRGF and AS, though this enhancement in the case of keratocytes was significantly higher with PRGF. PRGF eye drops showed a significant reduction of both inflammatory markers with respect to the initial inflammatory situation and to the AS treatment. Our results concluded that PRGF exerts more potent regenerative and anti-inflammatory effects than autologous serum on ocular surface fibroblasts treated with pro-inflammatory IL-1β and TNFα. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. Comparison of internal target volumes defined on 3-dimensional, 4-dimensonal, and cone-beam CT images of non-small-cell lung cancer

    Li F

    2016-11-01

    Full Text Available Fengxiang Li,1 Jianbin Li,1 Zhifang Ma,1 Yingjie Zhang,1 Jun Xing,1 Huanpeng Qi,1 Dongping Shang21Department of Radiation Oncology, 2Department of Big Bore CT Room, Shandong Cancer Hospital Affiliated to Shandong University, Shandong Academy of Medical Sciences, Jinan, Shandong, People’s Republic of ChinaPurpose: The purpose of this study was to compare the positional and volumetric differences of internal target volumes defined on three-dimensional computed tomography (3DCT, four-dimensional CT (4DCT, and cone-beam CT (CBCT images of non-small-cell lung cancer (NSCLC. Materials and methods: Thirty-one patients with NSCLC sequentially underwent 3DCT and 4DCT simulation scans of the thorax during free breathing. The first CBCT was performed and registered to the planning CT using the bony anatomy registration during radiotherapy. The gross tumor volumes were contoured on the basis of 3DCT, maximum intensity projection (MIP of 4DCT, and CBCT. CTV3D (clinical target volume, internal target volumes, ITVMIP and ITVCBCT, were defined with a 7 mm margin accounting for microscopic disease. ITV10 mm and ITV5 mm were defined on the basis of CTV3D: ITV10 mm with a 5 mm margin in left–right (LR, anterior–posterior (AP directions and 10 mm in cranial–caudal (CC direction; ITV5 mm with an isotropic internal margin (IM of 5 mm. The differences in the position, size, Dice’s similarity coefficient (DSC and inclusion relation of different volumes were evaluated.Results: The median size ratios of ITV10 mm, ITV5 mm, and ITVMIP to ITVCBCT were 2.33, 1.88, and 1.03, respectively, for tumors in the upper lobe and 2.13, 1.76, and 1.1, respectively, for tumors in the middle-lower lobe. The median DSCs of ITV10 mm, ITV5 mm, ITVMIP, and ITVCBCT were 0.6, 0.66, and 0.83 for all patients. The median percentages of ITVCBCT not included in ITV10 mm, ITV5 mm, and ITVMIP were 0.1%, 1.63%, and 15.21%, respectively, while the median percentages of ITV10 mm, ITV5 mm

  11. Probability of mediastinal involvement in non-small-cell lung cancer: a statistical definition of the clinical target volume for 3-dimensional conformal radiotherapy?

    Giraud, Philippe; De Rycke, Yann; Lavole, Armelle; Milleron, Bernard; Cosset, Jean-Marc; Rosenzweig, Kenneth E.

    2006-01-01

    Purpose: Conformal irradiation (3D-CRT) of non-small-cell lung carcinoma (NSCLC) is largely based on precise definition of the nodal clinical target volume (CTVn). A reduction of the number of nodal stations to be irradiated would facilitate tumor dose escalation. The aim of this study was to design a mathematical tool based on documented data to predict the risk of metastatic involvement for each nodal station. Methods and Materials: We reviewed the large surgical series published in the literature to identify the main pretreatment parameters that modify the risk of nodal invasion. The probability of involvement for the 17 nodal stations described by the American Thoracic Society (ATS) was computed from all these publications. Starting with the primary site of the tumor as the main characteristic, we built a probabilistic tree for each nodal station representing the risk distribution as a function of each tumor feature. Statistical analysis used the inversion of probability trees method described by Weinstein and Feinberg. Validation of the software based on 134 patients from two different populations was performed by receiver operator characteristic (ROC) curves and multivariate logistic regression. Results: Analysis of all of the various parameters of pretreatment staging relative to each level of the ATS map results in 20,000 different combinations. The first parameters included in the tree, depending on tumor site, were histologic classification, metastatic stage, nodal stage weighted as a function of the sensitivity and specificity of the diagnostic examination used (positron emission tomography scan, computed tomography scan), and tumor stage. Software is proposed to compute a predicted probability of involvement of each nodal station for any given clinical presentation. Double cross validation confirmed the methodology. A 10% cutoff point was calculated from ROC and logistic model giving the best prediction of mediastinal lymph node involvement. Conclusion

  12. Placental extract ameliorates non-alcoholic steatohepatitis (NASH by exerting protective effects on endothelial cells

    Akihiro Yamauchi

    2017-09-01

    Full Text Available Non-alcoholic steatohepatitis (NASH is a severe form of fatty liver disease that is defined by the presence of inflammation and fibrosis, ultimately leading to cirrhosis and hepatocellular carcinoma. Treatment with human placental extract (HPE reportedly ameliorates the hepatic injury. We evaluated the effect of HPE treatment in a mouse model of NASH. In the methione- and choline-deficient (MCD diet-induced liver injury model, fibrosis started from regions adjacent to the sinusoids. We administered the MCD diet with high-salt loading (8% NaCl in the drinking water to mice deficient in the vasoprotective molecule RAMP2 for 5 weeks, with or without HPE. In both the HPE and control groups, fibrosis was seen in regions adjacent to the sinusoids, but the fibrosis was less pronounced in the HPE-treated mice. Levels of TNF-α and MMP9 expression were also significantly reduced in HPE-treated mice, and oxidative stress was suppressed in the perivascular region. In addition, HPE dose-dependently increased survival of cultured endothelial cells exposed to 100 μM H2O2, and it upregulated expression of eNOS and the anti-apoptotic factors bcl-2 and bcl-xL. From these observations, we conclude that HPE ameliorates NASH-associated pathologies by suppressing inflammation, oxidative stress and fibrosis. These beneficially effects of HPE are in part attributable to its protective effects on liver sinusoidal endothelial cells. HPE could thus be an attractive therapeutic candidate with which to suppress progression from simple fatty liver to NASH.

  13. Postprandial dietary fatty acids exert divergent inflammatory responses in retinal-pigmented epithelium cells.

    Montserrat-de la Paz, Sergio; Naranjo, M Carmen; Bermudez, Beatriz; Lopez, Sergio; Moreda, Wenceslao; Abia, Rocio; Muriana, Francisco J G

    2016-03-01

    Postprandial triglyceride-rich lipoproteins (TRLs) lead to a complex series of events that are potentially oxidative and inflammatory. The main goal of this study was to characterize the influence of postprandial TRLs with different fatty acid compositions (mainly SFAs, MUFAs or MUFAs plus omega-3 PUFAs) on oxidative and inflammatory markers in RPE cells, which play a pivotal role in age-related macular degeneration (AMD). Compared to TRL-SFAs, TRL-MUFAs and TRL-MUFAs plus omega-3 PUFAs decreased the production of ROS and nitrite, and the gene expression and secretion of IL-1β, IL-6, TNF-α, IFNγ and VEGF. For the first time we show that postprandial TRLs are metabolic entities able to induce RPE oxidative stress and inflammation in a fatty acid-dependent manner, TRL-SFAs ⋙ TRL-MUFAs = TRL-MUFAs plus omega-3 PUFAs. These exciting findings open new opportunities for developing novel nutritional strategies with olive oil as the principal dietary source of oleic acid to prevent the development and progression of AMD.

  14. Caffeoylxanthiazonoside exerts cardioprotective effects during chronic heart failure via inhibition of inflammatory responses in cardiac cells.

    Yang, Bin; Wang, Fei; Cao, Huili; Liu, Guifang; Zhang, Yuean; Yan, Ping; Li, Bao

    2017-11-01

    Caffeoylxanthiazonoside (CYT) is an active constituent isolated from the fruit of the Xanthium strumarium L plant. The aim of the present study was to investigate the cardioprotective effects of oral administration of CYT on chronic heart failure (CHF) and its underlying mechanisms. A rat model of CHF was first established, and cardiac function indices, including the heart/body weight index, left heart/body weight index, fractional shortening (FS), ejection fraction (EF), cardiac output (CO) and heart rate (HR), were subsequently determined by cardiac ultrasound. Serum levels of lactate dehydrogenase (LDH) and creatine kinase (CK), and the levels of pro-inflammatory cytokines, including tumor necrosis factor (TNF)-α, interleukin (IL)-6 and IL-1β in heart tissues and cardiac microvascular endothelial cells (CMECs) were determined using ELISA. In addition, the protein expression levels of nuclear factor-κB (NF-κB) signaling pathway members were determined by western blotting in CMECs. The results demonstrated that oral administration of 10, 20, 40 mg/kg CYT significantly reduced cardiac hypertrophy and reversed FS, EF, CO and HR when compared with CHF model rats. In addition, CYT administration significantly decreased the levels of TNF-α, IL-6 and IL-1β in heart tissues, as well as serum LDH and CK levels. Furthermore, exposure of CMECs to 20, 40 and 80 µg/ml CYT significantly decreased the production of TNF-α, IL-1β and IL-6. The protein expression levels of cytoplasmic NF-κB p65 and IκB were upregulated, while nuclear NF-κB p65 was downregulated following treatment of CMECs with 20, 40 and 80 µg/ml CYT when compared with untreated CHF model controls. In conclusion, the results of the current study suggest that CYT demonstrates cardioprotective effects in CHF model rats by suppressing the expression of pro-inflammatory cytokines and the NF-κB signaling pathway.

  15. Zebularine exerts its antiproliferative activity through S phase delay and cell death in human malignant mesothelioma cells.

    Takemura, Yukitoshi; Satoh, Motohiko; Hatanaka, Kenichi; Kubota, Shunichiro

    2018-04-24

    Malignant mesothelioma is an asbestos-related aggressive tumor and current therapy remains ineffective. Zebularine as a DNA methyltransferase (DNMT) inhibitor has an anti-tumor effect in several human cancer cells. The aim of the present study was to investigate whether zebularine could induce antiproliferative effect in human malignant mesothelioma cells. Zebularine induced cell growth inhibition in a dose-dependent manner. In addition, zebularine dose-dependently decreased expression of DNMT1 in all malignant mesothelioma cells tested. Cell cycle analysis indicated that zebularine induced S phase delay. Zebularine also induced cell death in malignant mesothelioma cells. In contrast, zebularine did not induce cell growth inhibition and cell death in human normal fibroblast cells. These results suggest that zebularine has a potential for the treatment of malignant mesothelioma by inhibiting cell growth and inducing cell death.

  16. Human umbilical cord mesenchymal stem cells hUC-MSCs exert immunosuppressive activities through a PGE2-dependent mechanism.

    Chen, Ke; Wang, Ding; Du, Wei Ting; Han, Zhi-Bo; Ren, He; Chi, Ying; Yang, Shao Guang; Zhu, Delin; Bayard, Francis; Han, Zhong Chao

    2010-06-01

    Human umbilical-cord-derived mesenchymal stem cells (hUC-MSCs) constitute an attractive alternative to bone-marrow-derived MSCs for potential clinical applications because of easy preparation and lower risk of viral contamination. In this study, both proliferation of human peripheral blood mononuclear cells (hPBMCs) and their IFN-gamma production in response to mitogenic or allogeneic stimulus were effectively inhibited by hUC-MSCs. Co-culture experiments in transwell systems indicated that the suppression was largely mediated by soluble factor(s). Blocking experiments identified prostaglandin E(2) (PGE(2)) as the major factor, because inhibition of PGE(2) synthesis almost completely mitigated the immunosuppressive effects, whereas neutralization of TGF-beta, IDO, and NO activities had little effects. Moreover, the inflammatory cytokines, IFN-gamma and IL-1beta, produced by hPBMCs upon activation notably upregulated the expression of cyclooxygenase-2 (COX-2) and the production of PGE(2) by hUC-MSCs. In conclusion, our data have demonstrated for the first time the PGE(2)-mediated mechanism by which hUC-MSCs exert their immunomodulatory effects. Copyright 2010 Elsevier Inc. All rights reserved.

  17. Pomegranate exerts chemoprevention of experimentally induced mammary tumorigenesis by suppression of cell proliferation and induction of apoptosis.

    Bishayee, Anupam; Mandal, Animesh; Bhattacharyya, Piyali; Bhatia, Deepak

    2016-01-01

    Breast cancer is the second leading cause of cancer-related death in women in the United States and discovery and development of safe chemopreventive drugs is urgently needed. The fruit pomegranate (Punica granatum) is gaining importance because of its various health benefits. This study was initiated to investigate chemopreventive potential of a pomegranate emulsion (PE) against 7,12-dimethylbenz(a)anthracene (DMBA) rat mammary carcinogenesis. The animals were orally administered with PE (0.2-5.0 g/kg), starting 2 wk before and 16 wk following DMBA treatment. PE exhibited a striking reduction of DMBA-induced mammary tumor incidence, total tumor burden, and reversed histopathological changes. PE dose-dependently suppressed cell proliferation and induced apoptosis in mammary tumors. Immunohistochemical studies showed that PE increased intratumor Bax, decreased Bcl2 and manifested a proapoptotic shift in Bax/Bcl2 ratio. In addition, our gene expression study showed PE-mediated upregulation of Bad, caspase-3, caspase-7, caspase-9, poly (ADP ribose) polymerase and cytochrome c in mammary tumors. Thus, PE exerts chemoprevention of mammary carcinogenesis by suppressing cell proliferation and inducing apoptosis mediated through upregulation of Bax and downregulation of Bcl2 in concert with caspase cascades. Pomegranate bioactive phytoconstituents could be developed as a chemopreventive drug to reduce the risk of breast cancer.

  18. Salinomycin Exerts Anticancer Effects on PC-3 Cells and PC-3-Derived Cancer Stem Cells In Vitro and In Vivo

    Yunsheng Zhang

    2017-01-01

    Full Text Available Salinomycin is an antibiotic isolated from Streptomyces albus that selectively kills cancer stem cells (CSCs. However, the antitumor mechanism of salinomycin is unclear. This study investigated the chemotherapeutic efficacy of salinomycin in human prostate cancer PC-3 cells. We found that cytotoxicity of salinomycin to PC-3 cells was stronger than to nonmalignant prostate cell RWPE-1, and exposure to salinomycin induced G2/M phage arrest and apoptosis of PC-3 cells. A mechanistic study found salinomycin suppressed Wnt/β-catenin pathway to induce apoptosis of PC-3 cells. An in vivo experiment confirmed that salinomycin suppressed tumorigenesis in a NOD/SCID mice xenograft model generated from implanted PC-3 cells by inhibiting the Wnt/β-catenin pathway, since the total β-catenin protein level was reduced and the downstream target c-Myc level was significantly downregulated. We also showed that salinomycin, but not paclitaxel, triggered more apoptosis in aldehyde dehydrogenase- (ALDH- positive PC-3 cells, which were considered as the prostate cancer stem cells, suggesting that salinomycin may be a promising chemotherapeutic to target CSCs. In conclusion, this study suggests that salinomycin reduces resistance and relapse of prostate tumor by killing cancer cells as well as CSCs.

  19. Combining antiangiogenic therapy with adoptive cell immunotherapy exerts better antitumor effects in non-small cell lung cancer models.

    Shujing Shi

    Full Text Available INTRODUCTION: Cytokine-induced killer cells (CIK cells are a heterogeneous subset of ex-vivo expanded T lymphocytes which are characterized with a MHC-unrestricted tumor-killing activity and a mixed T-NK phenotype. Adoptive CIK cells transfer, one of the adoptive immunotherapy represents a promising nontoxic anticancer therapy. However, in clinical studies, the therapeutic activity of adoptive CIK cells transfer is not as efficient as anticipated. Possible explanations are that abnormal tumor vasculature and hypoxic tumor microenvironment could impede the infiltration and efficacy of lymphocytes. We hypothesized that antiangiogenesis therapy could improve the antitumor activity of CIK cells by normalizing tumor vasculature and modulating hypoxic tumor microenvironment. METHODS: We combined recombinant human endostatin (rh-endostatin and CIK cells in the treatment of lung carcinoma murine models. Intravital microscopy, dynamic contrast enhanced magnetic resonance imaging, immunohistochemistry, and flow cytometry were used to investigate the tumor vasculature and hypoxic microenvironment as well as the infiltration of immune cells. RESULTS: Our results indicated that rh-endostatin synergized with adoptive CIK cells transfer to inhibit the growth of lung carcinoma. We found that rh-endostatin normalized tumor vasculature and reduced hypoxic area in the tumor microenvironment. Hypoxia significantly inhibited the proliferation, cytotoxicity and migration of CIK cells in vitro and impeded the homing of CIK cells into tumor parenchyma ex vivo. Furthermore, we found that treatment with rh-endostatin significantly increased the homing of CIK cells and decreased the accumulation of suppressive immune cells in the tumor tissue. In addition, combination therapy produced higher level of tumor-infiltration lymphocytes compared with other treatments. CONCLUSIONS: Our results demonstrate that rh-endostatin improves the therapeutic effect of adoptive CIK cells

  20. Regulatory T Cell Induced by Poria cocos Bark Exert Therapeutic Effects in Murine Models of Atopic Dermatitis and Food Allergy

    Min-Jung Bae

    2016-01-01

    Full Text Available The prevalence of allergic disorders including atopic dermatitis (AD and food allergy (FA has increased dramatically in pediatric populations, but there is no effective drug available for their management. Therefore, trials are required for the development of safe therapeutic agents such as herbal medicines. We determined whether orally administered Poria cocos bark (PCB extract could exert immunosuppressive effects on allergic and inflammatory symptoms of AD and FA. For both AD, which was induced using house dust mite extract, and FA, which was induced by exposure to ovalbumin, model mice were orally treated with PCB extract for 62 days and 18 days, respectively. We also investigated the inductive effect of PCB extract on the generation and maintenance of Foxp3+CD4+ regulatory T cells (Tregs. The symptoms of AD and FA were ameliorated by the administration of PCB extract. Furthermore, PCB extract inhibited the Th2-related cytokines and increased the population of Foxp3+CD4+ Tregs in both AD and FA models. In ex vivo experiments, PCB extract promoted the functional differentiation of Foxp3+CD4+ Tregs, which is dependent on aryl hydrocarbon receptor activation. Thus, PCB extract has potential as an oral immune suppressor for the treatment of AD and FA through the generation of Tregs.

  1. Note on 3-dimensional Regge calculus

    Soda, Jiro

    1991-01-01

    We shall study 3-dimensional Regge calculus with concentrating the role of the Bianchi identity. As a result, the number of the physical variables is determined to be 12g - 12(g > 1). The reason why Rocek and Williams derived the exact result of Deser, Jackiw and 'tHooft is clarified. (author)

  2. Properties of 3-dimensional line location models

    Brimberg, Jack; Juel, Henrik; Schöbel, Anita

    2002-01-01

    We consider the problem of locating a line with respect to some existing facilities in 3-dimensional space, such that the sum of weighted distances between the line and the facilities is minimized. Measuring distance using the l\\_p norm is discussed, along with the special cases of Euclidean...

  3. On 3-Dimensional Stability of Reshaping Breakwaters

    Burcharth, Hans F.; Frigaard, Peter

    1989-01-01

    The paper deals with the 3-dimensional stability of the type of rubble mound breakwaters where reshaping of the mound due to wave action is foreseen in the design. Such breakwaters are commonly named sacrificial types and berm types. The latter is due to the relatively large volume of armour stones...

  4. Inhibition of Hypoxia Inducible Factor Alpha and Astrocyte-Elevated Gene-1 Mediates Cryptotanshinone Exerted Antitumor Activity in Hypoxic PC-3 Cells

    Hyo-Jeong Lee

    2012-01-01

    Full Text Available Although cryptotanshinone (CT was known to exert antitumor activity in several cancers, its molecular mechanism under hypoxia still remains unclear. Here, the roles of AEG-1 and HIF-1α in CT-induced antitumor activity were investigated in hypoxic PC-3 cells. CT exerted cytotoxicity against prostate cancer cells and suppressed HIF-1α accumulation and AEG-1 expression in hypoxic PC-3 cells. Also, AEG-1 was overexpressed in prostate cancer cells. Interestingly, HIF-1α siRNA transfection enhanced the cleavages of caspase-9,3, and PAPR and decreased expression of Bcl-2 and AEG1 induced by CT in hypoxic PC-3 cells. Of note, DMOG enhanced the stability of AEG-1 and HIF-1α during hypoxia. Additionally, CT significantly reduced cellular level of VEGF in PC-3 cells and disturbed tube formation of HUVECs. Consistently, ChIP assay revealed that CT inhibited the binding of HIF-1α to VEGF promoter. Furthermore, CT at 10 mg/kg suppressed the growth of PC-3 cells in BALB/c athymic nude mice by 46.4% compared to untreated control. Consistently, immunohistochemistry revealed decreased expression of Ki-67, CD34, VEGF, carbonic anhydrase IX, and AEG-1 indices in CT-treated group compared to untreated control. Overall, our findings suggest that CT exerts antitumor activity via inhibition of HIF-1α, AEG1, and VEGF as a potent chemotherapeutic agent.

  5. Bone Morphogenetic Protein-2, but Not Mesenchymal Stromal Cells, Exert Regenerative Effects on Canine and Human Nucleus Pulposus Cells

    Bach, Frances C.; Miranda-Bedate, Alberto; Van Heel, Ferdi W M; Riemers, Frank M.; Müller, Margot C M E; Creemers, Laura B.; Ito, Keita; Benz, Karin; Meij, Björn P.; Tryfonidou, Marianna A.

    2017-01-01

    Chronic back pain is related to intervertebral disc (IVD) degeneration and dogs are employed as animal models to develop growth factor- and cell-based regenerative treatments. In this respect, the differential effects of transforming growth factor beta-1 (TGF-β1) and bone morphogenetic protein-2

  6. Bone morphogenetic protein-2, but not mesenchymal stromal cells, exert regenerative effects on canine and human nucleus pulposus cells

    Bach, Frances; Miranda-Bedate, Alberto; van Heel, Ferdi; Riemers, Frank; Muller, Margot; Creemers, Laura; Ito, Keita; Benz, Karin; Meij, Björn; Tryfonidou, M

    2017-01-01

    Chronic back pain is related to intervertebral disc (IVD) degeneration and dogs are employed as animal models to develop growth factor- and cell-based regenerative treatments. In this respect, the differential effects of transforming growth factor beta-1 (TGF-β1) and bone morphogenetic protein-2

  7. Bone morphogenetic protein-2, but not mesenchymal stromal cells, exert regenerative effects on Canine and human nucleus pulposus cells

    Bach, F.C.; Miranda-Bedate, A.; Van Heel, F.W.M.; Riemers, F.M.; Müller, M.C.M.E.; Creemers, L.B.; Ito, K.; Benz, K.; Meij, B.P.; Tryfonidou, M.A.

    2017-01-01

    Chronic back pain is related to intervertebral disc (IVD) degeneration and dogs are employed as animal models to develop growth factor- and cell-based regenerative treatments. In this respect, the differential effects of transforming growth factor beta-1 (TGF-β1) and bone morphogenetic protein-2

  8. A cell-penetrating peptide analogue, P7, exerts antimicrobial activity against Escherichia coli ATCC25922 via penetrating cell membrane and targeting intracellular DNA.

    Li, Lirong; Shi, Yonghui; Cheng, Xiangrong; Xia, Shufang; Cheserek, Maureen Jepkorir; Le, Guowei

    2015-01-01

    The antibacterial activities and mechanism of a new P7 were investigated in this study. P7 showed antimicrobial activities against five harmful microorganisms which contaminate and spoil food (MIC=4-32 μM). Flow cytometry and scanning electron microscopy analyses demonstrated that P7 induced pore-formation on the cell surface and led to morphological changes but did not lyse cell. Confocal fluorescence microscopic observations and flow cytometry analysis expressed that P7 could penetrate the Escherichia coli cell membrane and accumulate in the cytoplasm. Moreover, P7 possessed a strong DNA binding affinity. Further cell cycle analysis and change in gene expression analysis suggested that P7 induced a decreased expression in the genes involved in DNA replication. Up-regulated expression genes encoding DNA damage repair. This study suggests that P7 could be applied as a candidate for the development of new food preservatives as it exerts its antibacterial activities by penetrating cell membranes and targets intracellular DNA. Copyright © 2014 Elsevier Ltd. All rights reserved.

  9. Neutron sample cell suitable for the diffraction of aligned biomaterials and capable of exerting up to 370 MPa of hydrostatic pressure

    Watson, M.J.; Nieh, M.-P.; Harroun, T.A.; Katsaras, J.

    2003-01-01

    We describe a temperature controlled sample cell suitable for the study of biomimetic materials (e.g., lipid bilayers) using neutron diffraction, and capable of exerting hydrostatic pressures of up to 370 MPa. The advantage of this sample cell, compared to previous high-pressure cells of its type, is that it allows for the use of samples aligned on a solid support which, compared to 'powder' or so-called liposomal preparations, requires only small amounts of sample and allows for the clear differentiation between in-plane and out-of-plane structure

  10. Lactobacillus casei Exerts Anti-Proliferative Effects Accompanied by Apoptotic Cell Death and Up-Regulation of TRAIL in Colon Carcinoma Cells

    Santarmaki, Valentina; Aindelis, Georgios; Tompoulidou, Evgenia; Lamprianidou, Eleftheria E.; Saxami, Georgia; Ypsilantis, Petros; Lampri, Evangeli S.; Simopoulos, Constantinos; Kotsianidis, Ioannis; Galanis, Alex; Kourkoutas, Yiannis; Dimitrellou, Dimitra; Chlichlia, Katerina

    2016-01-01

    Probiotic microorganisms such as lactic acid bacteria (LAB) exert a number of strain-specific health-promoting activities attributed to their immunomodulatory, anti-inflammatory and anti-carcinogenic properties. Despite recent attention, our understanding of the biological processes involved in the beneficial effects of LAB strains is still limited. To this end, the present study investigated the growth-inhibitory effects of Lactobacillus casei ATCC 393 against experimental colon cancer. Administration of live Lactobacillus casei (as well as bacterial components thereof) on murine (CT26) and human (HT29) colon carcinoma cell lines raised a significant concentration- and time-dependent anti-proliferative effect, determined by cell viability assays. Specifically, a dramatic decrease in viability of colon cancer cells co-incubated with 109 CFU/mL L. casei for 24 hours was detected (78% for HT29 and 52% for CT26 cells). In addition, live L. casei induced apoptotic cell death in both cell lines as revealed by annexin V and propidium iodide staining. The significance of the in vitro anti-proliferative effects was further confirmed in an experimental tumor model. Oral daily administration of 109 CFU live L. casei for 13 days significantly inhibited in vivo growth of colon carcinoma cells, resulting in approximately 80% reduction in tumor volume of treated mice. Tumor growth inhibition was accompanied by L. casei-driven up-regulation of the TNF-related apoptosis-inducing ligand TRAIL and down-regulation of Survivin. Taken together, these findings provide evidence for beneficial tumor-inhibitory, anti-proliferative and pro-apoptotic effects driven by this probiotic LAB strain. PMID:26849051

  11. Lactobacillus casei Exerts Anti-Proliferative Effects Accompanied by Apoptotic Cell Death and Up-Regulation of TRAIL in Colon Carcinoma Cells.

    Angeliki Tiptiri-Kourpeti

    Full Text Available Probiotic microorganisms such as lactic acid bacteria (LAB exert a number of strain-specific health-promoting activities attributed to their immunomodulatory, anti-inflammatory and anti-carcinogenic properties. Despite recent attention, our understanding of the biological processes involved in the beneficial effects of LAB strains is still limited. To this end, the present study investigated the growth-inhibitory effects of Lactobacillus casei ATCC 393 against experimental colon cancer. Administration of live Lactobacillus casei (as well as bacterial components thereof on murine (CT26 and human (HT29 colon carcinoma cell lines raised a significant concentration- and time-dependent anti-proliferative effect, determined by cell viability assays. Specifically, a dramatic decrease in viability of colon cancer cells co-incubated with 10(9 CFU/mL L. casei for 24 hours was detected (78% for HT29 and 52% for CT26 cells. In addition, live L. casei induced apoptotic cell death in both cell lines as revealed by annexin V and propidium iodide staining. The significance of the in vitro anti-proliferative effects was further confirmed in an experimental tumor model. Oral daily administration of 10(9 CFU live L. casei for 13 days significantly inhibited in vivo growth of colon carcinoma cells, resulting in approximately 80% reduction in tumor volume of treated mice. Tumor growth inhibition was accompanied by L. casei-driven up-regulation of the TNF-related apoptosis-inducing ligand TRAIL and down-regulation of Survivin. Taken together, these findings provide evidence for beneficial tumor-inhibitory, anti-proliferative and pro-apoptotic effects driven by this probiotic LAB strain.

  12. Lactobacillus casei Exerts Anti-Proliferative Effects Accompanied by Apoptotic Cell Death and Up-Regulation of TRAIL in Colon Carcinoma Cells.

    Tiptiri-Kourpeti, Angeliki; Spyridopoulou, Katerina; Santarmaki, Valentina; Aindelis, Georgios; Tompoulidou, Evgenia; Lamprianidou, Eleftheria E; Saxami, Georgia; Ypsilantis, Petros; Lampri, Evangeli S; Simopoulos, Constantinos; Kotsianidis, Ioannis; Galanis, Alex; Kourkoutas, Yiannis; Dimitrellou, Dimitra; Chlichlia, Katerina

    2016-01-01

    Probiotic microorganisms such as lactic acid bacteria (LAB) exert a number of strain-specific health-promoting activities attributed to their immunomodulatory, anti-inflammatory and anti-carcinogenic properties. Despite recent attention, our understanding of the biological processes involved in the beneficial effects of LAB strains is still limited. To this end, the present study investigated the growth-inhibitory effects of Lactobacillus casei ATCC 393 against experimental colon cancer. Administration of live Lactobacillus casei (as well as bacterial components thereof) on murine (CT26) and human (HT29) colon carcinoma cell lines raised a significant concentration- and time-dependent anti-proliferative effect, determined by cell viability assays. Specifically, a dramatic decrease in viability of colon cancer cells co-incubated with 10(9) CFU/mL L. casei for 24 hours was detected (78% for HT29 and 52% for CT26 cells). In addition, live L. casei induced apoptotic cell death in both cell lines as revealed by annexin V and propidium iodide staining. The significance of the in vitro anti-proliferative effects was further confirmed in an experimental tumor model. Oral daily administration of 10(9) CFU live L. casei for 13 days significantly inhibited in vivo growth of colon carcinoma cells, resulting in approximately 80% reduction in tumor volume of treated mice. Tumor growth inhibition was accompanied by L. casei-driven up-regulation of the TNF-related apoptosis-inducing ligand TRAIL and down-regulation of Survivin. Taken together, these findings provide evidence for beneficial tumor-inhibitory, anti-proliferative and pro-apoptotic effects driven by this probiotic LAB strain.

  13. Intravenous administration of mesenchymal stem cells exerts therapeutic effects on parkinsonian model of rats: Focusing on neuroprotective effects of stromal cell-derived factor-1α

    Tayra Judith

    2010-04-01

    Full Text Available Abstract Background Mesenchymal stem cells (MSCs are pluripotent stem cells derived from bone marrow with secretory functions of various neurotrophic factors. Stromal cell-derived factor-1α (SDF-1α is also reported as one of chemokines released from MSCs. In this research, the therapeutic effects of MSCs through SDF-1α were explored. 6-hydroxydopamine (6-OHDA, 20 μg was injected into the right striatum of female SD rats with subsequent administration of GFP-labeled MSCs, fibroblasts, (i.v., 1 × 107 cells, respectively or PBS at 2 hours after 6-OHDA injection. All rats were evaluated behaviorally with cylinder test and amphetamine-induced rotation test for 1 month with consequent euthanasia for immunohistochemical evaluations. Additionally, to explore the underlying mechanisms, neuroprotective effects of SDF-1α were explored using 6-OHDA-exposed PC12 cells by using dopamine (DA assay and TdT-mediated dUTP-biotin nick-end labeling (TUNEL staining. Results Rats receiving MSC transplantation significantly ameliorated behaviorally both in cylinder test and amphetamine-induced rotation test compared with the control groups. Correspondingly, rats with MSCs displayed significant preservation in the density of tyrosine hydroxylase (TH-positive fibers in the striatum and the number of TH-positive neurons in the substantia nigra pars compacta (SNc compared to that of control rats. In the in vitro study, SDF-1α treatment increased DA release and suppressed cell death induced by 6-OHDA administration compared with the control groups. Conclusions Consequently, MSC transplantation might exert neuroprotection on 6-OHDA-exposed dopaminergic neurons at least partly through anti-apoptotic effects of SDF-1α. The results demonstrate the potentials of intravenous MSC administration for clinical applications, although further explorations are required.

  14. Cancer cells mimic in vivo spatial-temporal cell-cycle phase distribution and chemosensitivity in 3-dimensional Gelfoam® histoculture but not 2-dimensional culture as visualized with real-time FUCCI imaging.

    Yano, Shuya; Miwa, Shinji; Mii, Sumiyuki; Hiroshima, Yukihiko; Uehara, Fuminaru; Kishimoto, Hiroyuki; Tazawa, Hiroshi; Zhao, Ming; Bouvet, Michael; Fujiwara, Toshiyoshi; Hoffman, Robert M

    2015-01-01

    The phase of the cell cycle can determine whether a cancer cell can respond to a given drug. We previously reported monitoring of real-time cell cycle dynamics of cancer cells throughout a live tumor, intravitally in live mice, using a fluorescence ubiquitination-based cell-cycle indicator (FUCCI). Approximately 90% of cancer cells in the center and 80% of total cells of an established tumor are in G0/G1 phase. Longitudinal real-time imaging demonstrated that cytotoxic agents killed only proliferating cancer cells at the surface and, in contrast, had little effect on quiescent cancer cells, which are the vast majority of an established tumor. Moreover, resistant quiescent cancer cells restarted cycling after cessation of chemotherapy. These results suggested why most drugs currently in clinical use, which target cancer cells in S/G2/M, are mostly ineffective on solid tumors. In the present report, we used FUCCI imaging and Gelfoam® collagen-sponge-gel histoculture, to demonstrate in real time, that the cell-cycle phase distribution of cancer cells in Gelfoam® and in vivo tumors is highly similar, whereby only the surface cells proliferate and interior cells are quiescent in G0/G1. This is in contrast to 2D culture where most cancer cells cycle. Similarly, the cancer cells responded similarly to toxic chemotherapy in Gelfoam® culture as in vivo, and very differently than cancer cells in 2D culture which were much more chemosensitive. Gelfoam® culture of FUCCI-expressing cancer cells offers the opportunity to image the cell cycle of cancer cells continuously and to screen for novel effective therapies to target quiescent cells, which are the majority in a tumor and which would have a strong probability to be effective in vivo.

  15. 3-dimensional interactive space (3DIS)

    Veitch, S.; Veitch, J.; West, S.J.

    1991-01-01

    This paper reports on the 3DIS security system which uses standard CCTV cameras to create 3-Dimensional detection zones around valuable assets within protected areas. An intrusion into a zone changes light values and triggers an alarm that is annunciated, while images from multiple cameras are recorded. 3DIS lowers nuisance alarm rates and provides superior automated surveillance capability. Performance is improved over 2-D systems because activity around, above or below the zone does to cause an alarm. Invisible 3-D zones protect assets as small as a pin or as large as a 747 jetliner. Detection zones are created by excising subspaces from the overlapping fields of view of two or more video cameras. Hundred of zones may co-exist, operating simultaneously. Intrusion into any 3-D zone will cause a coincidental change in light values, triggering an alarm specific to that space

  16. Targeting the Epidermal Growth Factor Receptor Can Counteract the Inhibition of Natural Killer Cell Function Exerted by Colorectal Tumor-Associated Fibroblasts

    Delfina Costa

    2018-05-01

    Full Text Available Mesenchymal stromal cells (MSC present in the tumor microenvironment [usually named tumor-associated fibroblasts (TAF] can exert immunosuppressive effects on T and natural killer (NK lymphocytes, favoring tumor immune escape. We have analyzed this mechanism in colorectal carcinoma (CRC and found that co-culture of NK cells with TAF can prevent the IL-2-mediated NKG2D upregulation. This leads to the impairment of NKG2D-mediated recognition of CRC cells, sparing the NK cell activation through DNAM1 or FcγRIIIA (CD16. In situ, TAF express detectable levels of epidermal growth factor receptor (EGFR; thus, the therapeutic anti-EGFR humanized antibody cetuximab can trigger the antibody-dependent cellular cytotoxicity of TAF, through the engagement of FcγRIIIA on NK cells. Importantly, in the tumor, we found a lymphoid infiltrate containing NKp46+CD3− NK cells, enriched in CD16+ cells. This population, sorted and cultured with IL-2, could be triggered via CD16 and via NKG2D. Of note, ex vivo NKp46+CD3− cells were able to kill autologous TAF; in vivo, this might represent a control mechanism to reduce TAF-mediated regulatory effect on NK cell function. Altogether, these findings suggest that MSC from the neoplastic mucosa (TAF of CRC patients can downregulate the immune cell recognition of CRC tumor cells. This immunosuppression can be relieved by the anti-EGFR antibody used in CRC immunotherapy.

  17. Targeting the Epidermal Growth Factor Receptor Can Counteract the Inhibition of Natural Killer Cell Function Exerted by Colorectal Tumor-Associated Fibroblasts

    Costa, Delfina; Venè, Roberta; Benelli, Roberto; Romairone, Emanuele; Scabini, Stefano; Catellani, Silvia; Rebesco, Barbara; Mastracci, Luca; Grillo, Federica; Minghelli, Simona; Loiacono, Fabrizio; Zocchi, Maria Raffaella; Poggi, Alessandro

    2018-01-01

    Mesenchymal stromal cells (MSC) present in the tumor microenvironment [usually named tumor-associated fibroblasts (TAF)] can exert immunosuppressive effects on T and natural killer (NK) lymphocytes, favoring tumor immune escape. We have analyzed this mechanism in colorectal carcinoma (CRC) and found that co-culture of NK cells with TAF can prevent the IL-2-mediated NKG2D upregulation. This leads to the impairment of NKG2D-mediated recognition of CRC cells, sparing the NK cell activation through DNAM1 or FcγRIIIA (CD16). In situ, TAF express detectable levels of epidermal growth factor receptor (EGFR); thus, the therapeutic anti-EGFR humanized antibody cetuximab can trigger the antibody-dependent cellular cytotoxicity of TAF, through the engagement of FcγRIIIA on NK cells. Importantly, in the tumor, we found a lymphoid infiltrate containing NKp46+CD3− NK cells, enriched in CD16+ cells. This population, sorted and cultured with IL-2, could be triggered via CD16 and via NKG2D. Of note, ex vivo NKp46+CD3− cells were able to kill autologous TAF; in vivo, this might represent a control mechanism to reduce TAF-mediated regulatory effect on NK cell function. Altogether, these findings suggest that MSC from the neoplastic mucosa (TAF) of CRC patients can downregulate the immune cell recognition of CRC tumor cells. This immunosuppression can be relieved by the anti-EGFR antibody used in CRC immunotherapy. PMID:29910806

  18. Ibuprofen delivered by poly(lactic-co-glycolic acid) (PLGA) nanoparticles to human gastric cancer cells exerts antiproliferative activity at very low concentrations

    Bonelli, Patrizia; Tuccillo, Franca M; Federico, Antonella; Napolitano, Maria; Borrelli, Antonella; Melisi, Daniela; Rimoli, Maria G; Palaia, Raffaele; Arra, Claudio; Carinci, Francesco

    2012-01-01

    Purpose Epidemiological, clinical, and laboratory studies have suggested that ibuprofen, a commonly used nonsteroidal anti-inflammatory drug, inhibits the promotion and proliferation of certain tumors. Recently, we demonstrated the antiproliferative effects of ibuprofen on the human gastric cancer cell line MKN-45. However, high doses of ibuprofen were required to elicit these antiproliferative effects in vitro. The present research compared the antiproliferative effects of ibuprofen delivered freely and released by poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) in MKN-45 cells. Methods MKN-45 human gastric adenocarcinoma cells were treated with ibuprofen-loaded PLGA NPs. The proliferation of MKN-45 cells was then assessed by cell counting. The uptake of NPs was imaged by fluorescence microscopy and flow cytometry. The release of ibuprofen from ibuprofen-loaded PLGA NPs in the cells was evaluated by gas chromatography–mass spectrometry. Results Dramatic inhibition of cellular proliferation was observed in cells treated with ibuprofen-loaded PLGA NPs versus those treated with free ibuprofen at the same concentration. The localization of NPs was cytoplasmic. The initiation of ibuprofen release was rapid, commencing within 2 hours, and then increased slowly over time, reaching a maximum concentration at 24 hours. The inhibition of proliferation was confirmed to be due to the intracellular release of ibuprofen from the NPs. Using PLGA NPs as carriers, ibuprofen exerted an antiproliferative activity at concentrations > 100 times less than free ibuprofen, suggesting greater efficiency and less cellular toxicity. In addition, when carried by PLGA NPs, ibuprofen more quickly induced the expression of transcripts involved in proliferation and invasiveness processes. Conclusion Ibuprofen exerted an antiproliferative effect on MKN-45 cells at low concentrations. This effect was achieved using PLGA NPs as carriers of low doses of ibuprofen. PMID:23180963

  19. A 4-Phenoxyphenol Derivative Exerts Inhibitory Effects on Human Hepatocellular Carcinoma Cells through Regulating Autophagy and Apoptosis Accompanied by Downregulating α-Tubulin Expression

    Wen-Tsan Chang

    2017-05-01

    Full Text Available Hepatocellular carcinoma (HCC is a leading cancer worldwide. Advanced HCCs are usually resistant to anticancer drugs, causing unsatisfactory chemotherapy outcomes. In this study, we showed that a 4-phenoxyphenol derivative, 4-[4-(4-hydroxyphenoxyphenoxy]phenol (4-HPPP, exerts an inhibitory activity against two HCC cell lines, Huh7 and Ha22T. We further investigated the anti-HCC activities of 4-HPPP, including anti-proliferation and induction of apoptosis. Our results showed that higher dosage of 4-HPPP downregulates the expression of α-tubulin and causes nuclear enlargement in both the Huh-7 and Ha22T cell lines. Interestingly, the colony formation results showed a discrepancy in the inhibitory effect of 4-HPPP on HCC and rat liver epithelial Clone 9 cells, suggesting the selective cytotoxicity of 4-HPPP toward HCC cells. Furthermore, the cell proliferation and apoptosis assay results illustrated the differences between the two HCC cell lines. The results of cellular proliferation assays, including trypan blue exclusion and colony formation, revealed that 4-HPPP inhibits the growth of Huh7 cells, but exerts less cytotoxicity in Ha22T cells. Furthermore, the annexin V assay performed for detecting the apoptosis showed similar results. Western blotting results showed 4-HPPP caused the increase of pro-apoptotic factors including cleaved caspase-3, Bid and Bax in HCC cells, especially in Huh-7. Furthermore, an increase of autophagy-associated protein microtubule-associated protein-1 light chain-3B (LC3B-II and the decrease of Beclin-1 and p62/SQSTM1 were observed following 4-HPPP treatment. Additionally, the level of γH2A histone family, member X (γH2AX, an endogenous DNA damage biomarker, was dramatically increased in Huh7 cells after 4-HPPP treatment, suggesting the involvement of DNA damage pathway in 4-HPPP-induced apoptosis. On the contrary, the western blotting results showed that treatment up-regulates pro-survival proteins, including the

  20. 17β-estradiol exerts anticancer effects in anoikis-resistant hepatocellular carcinoma cell lines by targeting IL-6/STAT3 signaling

    Lee, Seulki, E-mail: sl10f@naver.com [Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 110-799 (Korea, Republic of); Lee, Minjong, E-mail: minjonglee2@naver.com [Division of Gastroenterology, Department of Internal Medicine, Kangwon National University Hospital, 156 Baengnyeong-ro, Chuncheon-si, Gangwon-do (Korea, Republic of); Kim, Jong Bin, E-mail: kkimjp@hanmail.net [Hormel Institute, University of Minnesota, 801 16th Ave NE, Austin, MN, 55912 (United States); Jo, Ara, E-mail: loveara0315@naver.com [Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 110-799 (Korea, Republic of); Cho, Eun Ju, E-mail: creatioex@gmail.com [Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 110-799 (Korea, Republic of); Yu, Su Jong, E-mail: ydoctor2@hanmail.net [Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 110-799 (Korea, Republic of); Lee, Jeong-Hoon, E-mail: pindra@empal.com [Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 110-799 (Korea, Republic of); Yoon, Jung-Hwan, E-mail: yoonjh@snu.ac.kr [Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 110-799 (Korea, Republic of); Kim, Yoon Jun, E-mail: yoonjun@snu.ac.kr [Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 110-799 (Korea, Republic of)

    2016-05-13

    17β-Estradiol (E2) has been proven to exert protective effects against HCC; however, its mechanism on HCC proliferation and suppression of invasion remains to be further explored. Because HCC up-regulates serum Interleukin-6 (IL-6) levels and Signal Transducer and Activator of Transcription 3 (STAT3), molecular agents that attenuate IL-6/STAT3 signaling can potentially suppress HCC development. In this study, we examined involvement of E2 in anoikis resistance that induces invasion capacities and chemo-resistance. Huh-BAT and HepG2 cells grown under anchorage-independent condition were selected. The anoikis-resistant (AR) cells showed stronger chemo-resistance against sorafenib, doxorubicin, 5-fluorouracil and cisplatin compared to adherent HCC cells. AR HCC cells exhibited decreased expression of E-cadherin and increased expression of the N-cadherin and vimentin compared to adherent HCC cells. We then demonstrated that E2 suppressed cell proliferation in AR HCC cells. IL-6 treatment enhanced invasive characteristics, and E2 reversed it. Regarding mechanism of E2, it decreased in the phosphorylation of STAT3 that overexpressed on AR HCC cells. The inhibitory effect of E2 on cell growth was accompanied with cell cycle arrest at G2/M phase and caspase-3/9/PARP activation through c-Jun N-terminal Kinase (JNK) phosphorylation. Taken together, these findings suggested that E2 inhibited the proliferation of AR HCC cells through down-regulation of IL-6/STAT3 signaling. Thus, E2 can be a potential therapeutic drug for treatment of metastatic or chemo-resistant HCC. -- Highlights: •Anoikis-resistant HCC cells characterized chemo-resistant and metastatic potentials. •17β-Estradiol down-regulated IL-6/STAT3 signaling in anoikis-resistant HCC cells. •17β-Estradiol suppressed cell proliferation by inducing G2/M phase arrest and apoptosis though JNK phosphorylation.

  1. Nickel oxide nanoparticles exert cytotoxicity via oxidative stress and induce apoptotic response in human liver cells (HepG2).

    Ahamed, Maqusood; Ali, Daoud; Alhadlaq, Hisham A; Akhtar, Mohd Javed

    2013-11-01

    Increasing use of nickel oxide nanoparticles (NiO NPs) necessitates an improved understanding of their potential impact on human health. Previously, toxic effects of NiO NPs have been investigated, mainly on airway cells. However, information on effect of NiO NPs on human liver cells is largely lacking. In this study, we investigated the reactive oxygen species (ROS) mediated cytotoxicity and induction of apoptotic response in human liver cells (HepG2) due to NiO NPs exposure. Prepared NiO NPs were crystalline and spherical shaped with an average diameter of 44 nm. NiO NPs induced cytotoxicity (cell death) and ROS generation in HepG2 cells in dose-dependent manner. Further, ROS scavenger vitamin C reduced cell death drastically caused by NiO NPs exposure indicating that oxidative stress plays an important role in NiO NPs toxicity. Micronuclei induction, chromatin condensation and DNA damage in HepG2 cells treated with NiO NPs suggest that NiO NPs induced cell death via apoptotic pathway. Quantitative real-time PCR analysis showed that following the exposure of HepG2 cells to NiO NPs, the expression level of mRNA of apoptotic genes (bax and caspase-3) were up-regulated whereas the expression level of anti-apoptotic gene bcl-2 was down-regulated. Moreover, activity of caspase-3 enzyme was also higher in NiO NPs treated cells. To the best of our knowledge this is the first report demonstrating that NiO NPs caused cytotoxicity via ROS and induced apoptosis in HepG2 cells, which is likely to be mediated through bax/bcl-2 pathway. This work warrants careful assessment of Ni NPs before their commercial and industrial applications. Copyright © 2013 Elsevier Ltd. All rights reserved.

  2. CEBPA exerts a specific and biologically important proapoptotic role in pancreatic β cells through its downstream network targets

    Barbagallo, Davide; Condorelli, Angelo Giuseppe; Piro, Salvatore

    2014-01-01

    Transcription factor CEBPA has been widely studied for its involvement in hematopoietic cell differentiation and causal role in hematological malignancies. We demonstrate here that it also performs a causal role in cytokine-induced apoptosis of pancreas β cells. Treatment of two mouse pancreatic ...

  3. Accumulation of a soluble form of human nectin-2 is required for exerting the resistance against herpes simplex virus type 2 infection in transfected cells.

    Fujimoto, Y; Ozaki, K; Iwamori, N; Takakuwa, H; Ono, E

    2016-03-01

    Cell entry of herpes simplex virus type 2 (HSV-2) requires the interaction of viral glycoprotein D (gD) with the receptor nectin-1 and herpesvirus entry mediator (HVEM). In addition, it is known that nectin-2 is also functional as a receptor for HSV-2, although the binding to the gD is weak. To examine an antiviral potential of a soluble form of human nectin-2 (hNectin-2Ig), transfected Vero cells expressing the entire ectodomain of nectin-2 fused to the Fc portion of human IgG were established. Specific binding of hNectin-2Ig to HSV-2 gD was confirmed by ELISA. Competitive ELISA demonstrated that accumulation of hNectin-2Ig in transfected cells increased significantly in a cell culture time dependent manner. Viral growth of several HSV-2 strains was significantly inhibited in the transfected cells that were cultured for 72 hr compared with control Vero cells, but not in cells that were cultured for 24 hr. These results indicate that accumulation of a soluble form of nectin-2 is required for exerting the resistance against HSV-2 infection.

  4. Imatinib mesylate exerts anti-proliferative effects on osteosarcoma cells and inhibits the tumour growth in immunocompetent murine models.

    Bérengère Gobin

    Full Text Available Osteosarcoma is the most common primary malignant bone tumour characterized by osteoid production and/or osteolytic lesions of bone. A lack of response to chemotherapeutic treatments shows the importance of exploring new therapeutic methods. Imatinib mesylate (Gleevec, Novartis Pharma, a tyrosine kinase inhibitor, was originally developed for the treatment of chronic myeloid leukemia. Several studies revealed that imatinib mesylate inhibits osteoclast differentiation through the M-CSFR pathway and activates osteoblast differentiation through PDGFR pathway, two key cells involved in the vicious cycle controlling the tumour development. The present study investigated the in vitro effects of imatinib mesylate on the proliferation, apoptosis, cell cycle, and migration ability of five osteosarcoma cell lines (human: MG-63, HOS; rat: OSRGA; mice: MOS-J, POS-1. Imatinib mesylate was also assessed as a curative and preventive treatment in two syngenic osteosarcoma models: MOS-J (mixed osteoblastic/osteolytic osteosarcoma and POS-1 (undifferentiated osteosarcoma. Imatinib mesylate exhibited a dose-dependent anti-proliferative effect in all cell lines studied. The drug induced a G0/G1 cell cycle arrest in most cell lines, except for POS-1 and HOS cells that were blocked in the S phase. In addition, imatinib mesylate induced cell death and strongly inhibited osteosarcoma cell migration. In the MOS-J osteosarcoma model, oral administration of imatinib mesylate significantly inhibited the tumour development in both preventive and curative approaches. A phospho-receptor tyrosine kinase array kit revealed that PDGFRα, among 7 other receptors (PDFGFRβ, Axl, RYK, EGFR, EphA2 and 10, IGF1R, appears as one of the main molecular targets for imatinib mesylate. In the light of the present study and the literature, it would be particularly interesting to revisit therapeutic evaluation of imatinib mesylate in osteosarcoma according to the tyrosine-kinase receptor

  5. Anti-podocalyxin antibody exerts antitumor effects via antibody-dependent cellular cytotoxicity in mouse xenograft models of oral squamous cell carcinoma.

    Itai, Shunsuke; Ohishi, Tomokazu; Kaneko, Mika K; Yamada, Shinji; Abe, Shinji; Nakamura, Takuro; Yanaka, Miyuki; Chang, Yao-Wen; Ohba, Shun-Ichi; Nishioka, Yasuhiko; Kawada, Manabu; Harada, Hiroyuki; Kato, Yukinari

    2018-04-27

    Podocalyxin (PODXL) overexpression is associated with progression, metastasis, and poor outcomes in cancers. We recently produced the novel anti-PODXL monoclonal antibody (mAb) PcMab-47 (IgG 1 , kappa). Herein, we engineered PcMab-47 into 47-mG 2a , a mouse IgG 2a -type mAb, to add antibody-dependent cellular cytotoxicity (ADCC). We further developed 47-mG 2a -f, a core fucose-deficient type of 47-mG 2a to augment its ADCC. Immunohistochemical analysis of oral cancer tissues using PcMab-47 and 47-mG 2a revealed that the latter stained oral squamous cell carcinoma (OSCC) cells in a cytoplasmic pattern at a much lower concentration. PcMab-47 and 47-mG 2a detected PODXL in 163/201 (81.1%) and in 197/201 (98.0%) OSCC samples, respectively. 47-mG 2a -f also detected PODXL in OSCCs at a similar frequency as 47-mG 2a . In vitro analysis revealed that both 47-mG 2a and 47-mG 2a -f exhibited strong complement-dependent cytotoxicity (CDC) against CHO/hPODXL cells. In contrast, 47-mG 2a -f exhibited much stronger ADCC than 47-mG 2a against OSCC cells, indicating that ADCC and CDC of those anti-PODXL mAbs depend on target cells. In vivo analysis revealed that both 47-mG 2a and 47-mG 2a -f exerted antitumor activity in CHO/hPODXL xenograft models at a dose of 100 μg or 500 μg/mouse/week administered twice. 47-mG 2a -f, but not 47-mG 2a , exerted antitumor activity in SAS and HSC-2 xenograft models at a dose of 100 μg/mouse/week administered three times. Although both 47-mG 2a and 47-mG 2a -f exerted antitumor activity in HSC-2 xenograft models at a dose of 500 μg/mouse/week administered twice, 47-mG 2a -f also showed higher antitumor activity than 47-mG 2a . These results suggested that a core fucose-deficient anti-PODXL mAb could be useful for antibody-based therapy against PODXL-expressing OSCCs.

  6. Esculetin exerts anti-proliferative effects against non-small-cell lung carcinoma by suppressing specificity protein 1 in vitro.

    Lee, Ra H; Jeon, Young-Joo; Cho, Jin H; Jang, Jeong-Yun; Kong, Il-Keun; Kim, Seok-Ho; Kim, MinSeok S; Chung, Hak-Jae; Oh, Keon B; Park, Seon-Min; Shin, Jae-Cheon; Seo, Jae-Min; Ko, Sungho; Shim, Jung-Hyun; Chae, Jung-Il

    2017-01-01

    Esculetin, a coumarin derivative, is a phenolic compound isolated from Artemisia capillaris, Citrus limonia, and Euphorbia lathyris. Although it has been reported to have anti-inflammatory, anti-oxidant, and anti-proliferative activities in several human cancers, its anti-proliferative activity against non-small-cell lung carcinoma (NSCLC) and the molecular mechanisms involved have not been adequately elucidated. In this study, we used two NSCLC cell lines (NCI-H358 and NCI-H1299) to investigate the anti-proliferative activity and apoptotic effect of esculetin. Our data showed that esculetin-treated cells exhibited reduced proliferation and apoptotic cell morphologies. Intriguingly, the transcription factor specificity protein 1 (Sp1) was significantly suppressed by esculetin in a dose- and time-dependent manner. Furthermore, the levels of p27 and p21, two key regulators of the cell cycle, were up-regulated by the esculetin-mediated down-regulation of Sp1; the level of a third cell-cycle regulator, survivin, was decreased, resulting in caspase-dependent apoptosis. Therefore, we conclude that esculetin could be a potent anti-proliferative agent in patients with NSCLC.

  7. Overexpression of Notch ligand Delta-like-1 by dendritic cells enhances their immunoregulatory capacity and exerts antiallergic effects on Th2-mediated allergic asthma in mice.

    Lee, Chen-Chen; Lin, Chu-Lun; Leu, Sy-Jye; Lee, Yueh-Lun

    2018-02-01

    Dendritic cells (DCs) are professional antigen-presenting cells, and Notch ligand Delta-like-1 (DLL1) on DCs was implicated in type 1T helper (Th1) differentiation. In this study, we produced genetically engineered bone marrow-derived DCs that expressed DLL1 (DLL1-DCs) by adenoviral transduction. DLL1-DCs exerted a fully mature phenotype, and had positive effects on expression levels of interleukin (IL)-12 and costimulatory molecules. Coculture of allogeneic T cells with ovalbumin (OVA)-pulsed DLL1-DCs enhanced T cell proliferative responses and promoted Th1 cell differentiation. Furthermore, adoptive transfer of OVA-stimulated DLL1-DCs into asthmatic mice alleviated the cardinal features of allergic asthma, including immunoglobulin E (IgE) production, airway hyperresponsiveness (AHR), airway inflammation, and production of Th2-type cytokines. Notably, enhanced levels of the Th1-biased IgG 2a response and interferon (IFN)-γ production were observed in these mice. Taken together, these data indicate that DLL1-DCs promoted Th1 cell development to alter the Th1/Th2 ratio and ameliorate Th2-mediated allergic asthma in mice. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Ibuprofen delivered by poly(lactic-co-glycolic acid (PLGA nanoparticles to human gastric cancer cells exerts antiproliferative activity at very low concentrations

    Bonelli P

    2012-11-01

    concentration at 24 hours. The inhibition of proliferation was confirmed to be due to the intracellular release of ibuprofen from the NPs. Using PLGA NPs as carriers, ibuprofen exerted an antiproliferative activity at concentrations > 100 times less than free ibuprofen, suggesting greater efficiency and less cellular toxicity. In addition, when carried by PLGA NPs, ibuprofen more quickly induced the expression of transcripts involved in proliferation and invasiveness processes.Conclusion: Ibuprofen exerted an antiproliferative effect on MKN-45 cells at low concentrations. This effect was achieved using PLGA NPs as carriers of low doses of ibuprofen.Keywords: nonsteroidal anti-inflammatory drug (NSAID, proliferation, uptake, MKN-45 cells

  9. Stevia rebaudiana ethanolic extract exerts better antioxidant properties and antiproliferative effects in tumour cells than its diterpene glycoside stevioside.

    López, Víctor; Pérez, Sergio; Vinuesa, Arturo; Zorzetto, Christian; Abian, Olga

    2016-04-01

    Steviol glycosides are currently being used as natural sweeteners by the food industry and Stevia rebaudiana has long been used as a sweet plant in South America for patients suffering from diabetes. In this study, a Stevia rebaudiana ethanolic extract (SREE) was prepared, analysed and tested for antioxidant activity in terms of free radical scavenging properties and antiproliferative effects in cervix (HeLa), pancreatic (MiaPaCa-2) and colonic (HCT116) cancer cells. The antiproliferative mechanism was confirmed by testing the effects on cyclin D1-CDK4. Bioassays were also performed for the diterpene glycoside stevioside. Our results demonstrate that the extract acts as an antioxidant being able to scavenge free radicals, but this activity was not due to stevioside. The extract also induced cell death in the three cell lines, being more active against cervix cancer cells (HeLa); however, the concentration of stevioside needed to produce antiproliferative effects was higher than the amount of steviol glycosides found in a lower dose of extract inducing cell death. In addition, the extract clearly inhibited CDK4 whereas stevioside did not, concluding that the antiproliferative activity of stevia may be due to inhibition of cyclin-dependent kinases performed by other compounds of the extract.

  10. Betulinic Acid Exerts Cytotoxic Activity Against Multidrug-Resistant Tumor Cells via Targeting Autocrine Motility Factor Receptor (AMFR

    Mohamed E. M. Saeed

    2018-05-01

    Full Text Available Betulinic acid (BetA is a naturally occurring pentacyclic triterpene isolated from the outer bark of white-barked birch trees and many other medicinal plants. Here, we studied betulinic acid's cytotoxic activity against drug-resistant tumor cell lines. P-glycoprotein (MDR1/ABCB1 and BCRP (ABCG2 are known ATP-binding cassette (ABC drug transporters that mediating MDR. ABCB5 is a close relative to ABCB1, which also mediates MDR. Constitutive activation of the EGF receptor is tightly linked to the development of chemotherapeutic resistance. BetA inhibited P-gp, BCRP, ABCB5 and mutation activated EGFR overexpressing cells with similar efficacy as their drug-sensitive parental counterparts. Furthermore, the mRNA expressions of ABCB1, BCRP, ABCB5 and EGFR were not related to the 50% inhibition concentrations (IC50 for BetA in a panel of 60 cell lines of the National Cancer Institute (NCI, USA. In addition to well-established MDR mechanisms, we attempted to identify other molecular mechanisms that play a role in mediating BetA's cytotoxic activity. For this reason, we performed COMPARE and hierarchical cluster analyses of the transcriptome-wide microarray-based mRNA expression of the NCI cell lines panel. Various genes significantly correlating to BetA's activity were involved in different biological processes, e.g., cell cycle regulation, microtubule formation, signal transduction, transcriptional regulation, chromatin remodeling, cell adhesion, tumor suppression, ubiquitination and proteasome degradation. Immunoblotting and in silico analyses revealed that the inhibition of AMFR activity might be one of the mechanisms for BetA to overcome MDR phenotypes. In conclusion, BetA may have therapeutic potential for the treatment of refractory tumors.

  11. CEBPA exerts a specific and biologically important proapoptotic role in pancreatic β cells through its downstream network targets

    Barbagallo, Davide; Condorelli, Angelo Giuseppe; Piro, Salvatore; Parrinello, Nunziatina; Fløyel, Tina; Ragusa, Marco; Rabuazzo, Agata Maria; Størling, Joachim; Purrello, Francesco; Di Pietro, Cinzia; Purrello, Michele

    2014-01-01

    Transcription factor CEBPA has been widely studied for its involvement in hematopoietic cell differentiation and causal role in hematological malignancies. We demonstrate here that it also performs a causal role in cytokine-induced apoptosis of pancreas β cells. Treatment of two mouse pancreatic α and β cell lines (αTC1-6 and βTC1) with proinflammatory cytokines IL-1β, IFN-γ, and TNF-α at doses that specifically induce apoptosis of βTC1 significantly increased the amount of mRNA and protein encoded by Cebpa and its proapoptotic targets, Arl6ip5 and Tnfrsf10b, in βTC1 but not in αTC1-6. Cebpa knockdown in βTC1 significantly decreased cytokine-induced apoptosis, together with the amount of Arl6ip5 and Tnfrsf10b. Analysis of the network comprising CEBPA, its targets, their first interactants, and proteins encoded by genes known to regulate cytokine-induced apoptosis in pancreatic β cells (genes from the apoptotic machinery and from MAPK and NFkB pathways) revealed that CEBPA, ARL6IP5, TNFRSF10B, TRAF2, and UBC are the top five central nodes. In silico analysis further suggests TRAF2 as trait d'union node between CEBPA and the NFkB pathway. Our results strongly suggest that Cebpa is a key regulator within the apoptotic network activated in pancreatic β cells during insulitis, and Arl6ip5, Tnfrsf10b, Traf2, and Ubc are key executioners of this program. PMID:24943845

  12. Arctigenin exerts anti-colitis efficacy through inhibiting the differentiation of Th1 and Th17 cells via an mTORC1-dependent pathway.

    Wu, Xin; Dou, Yannong; Yang, Yan; Bian, Difei; Luo, Jinque; Tong, Bei; Xia, Yufeng; Dai, Yue

    2015-08-15

    Arctigenin, the main effective constituent of Arctium lappa L. fruit, has previously been proven to dramatically attenuate dextran sulfate sodium (DSS)-induced colitis in mice, a frequently used animal model of inflammatory bowel disease (IBD). As Th1 and Th17 cells play a crucial role in the pathogenesis of IBD, the present study addressed whether and how arctigenin exerted anti-colitis efficacy by interfering with the differentiation and activation of Th1/Th17 cells. In vitro, arctigenin was shown to markedly inhibit the differentiation of Th17 cells from naïve T cells, and moderately inhibit the differentiation of Th1 cells, which was accompanied by lowered phosphorylation of STAT3 and STAT4, respectively. In contrast, arctigenin was lack of marked effect on the differentiation of either Th2 or regulatory T cells. Furthermore, arctigenin was shown to suppress the mammalian target of rapamycin complex 1 (mTORC1) pathway in T cells as demonstrated by down-regulated phosphorylation of the downstream target genes p70S6K and RPS6, and it functioned independent of two well-known upstream kinases PI3K/AKT and ERK. Arctigenin was also able to inhibit the activity of mTORC1 by dissociating raptor from mTOR. Interestingly, the inhibitory effect of arctigenin on T cell differentiation disappeared under a status of mTORC1 overactivation via knockdown of tuberous sclerosis complex 2 (TSC2, a negative regulator of mTORC1) or pretreatment of leucine (an agonist of mTOR). In DSS-induced mice, the inhibition of Th1/Th17 responses and anti-colitis effect of arctigenin were abrogated by leucine treatment. In conclusion, arctigenin ameliorates colitis through down-regulating the differentiation of Th1 and Th17 cells via mTORC1 pathway. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. Resveratrol and Estradiol Exert Disparate Effects on Cell Migration, Cell Surface Actin Structures, and Focal Adhesion Assembly in MDA-MB-231 Human Breast Cancer Cells

    Nicolas G. Azios

    2005-02-01

    Full Text Available Resveratrol, a grape polyphenol, is thought to be a cancer preventive, yet its effects on metastatic breast cancer are relatively unknown. Since cancer cell invasion is dependent on cell migration, the chemotactic response of MDA-MB-231 metastatic human breast cancer cells to resveratrol, estradiol (E2, or epidermal growth factor (EGF was investigated. Resveratrol decreased while E2 and EGF increased directed cell migration. Resveratrol may inhibit cell migration by altering the cytoskeleton. Resveratrol induced a rapid global array of filopodia and decreased focal adhesions and focal adhesion kinase (FAK activity. E2 or EGF treatment did not affect filopodia extension but increased lamellipodia and associated focal adhesions that are integral for cell migration. Combined resveratrol and E2 treatment resulted in a filopodia and focal adhesion response similar to resveratrol alone. Combined resveratrol and EGF resulted in a lamellipodia and focal adhesion response similar to EGF alone. E2 and to a lesser extent resveratrol increased EGFR activity. The cytoskeletal changes and EGFR activity in response to E2 were blocked by EGFR1 inhibitor indicating that E2 may increase cell migration via crosstalk with EGFR signaling. These data suggest a promotional role for E2 in breast cancer cell migration but an antiestrogenic, preventative role for resveratrol.

  14. Vaccinium bracteatum Thunb. Exerts Anti-Inflammatory Activity by Inhibiting NF-κB Activation in BV-2 Microglial Cells.

    Kwon, Seung-Hwan; Ma, Shi-Xun; Ko, Yong-Hyun; Seo, Jee-Yeon; Lee, Bo-Ram; Lee, Taek Hwan; Kim, Sun Yeou; Lee, Seok-Yong; Jang, Choon-Gon

    2016-09-01

    This study was designed to evaluate the pharmacological effects of Vaccinium bracteatum Thunb. methanol extract (VBME) on microglial activation and to identify the underlying mechanisms of action of these effects. The anti-inflammatory properties of VBME were studied using lipopolysaccharide (LPS)-stimulated BV-2 microglial cells. We measured the production of nitric oxide (NO), inducible NO synthase (iNOS), cyclooxygenase (COX)-2, prostaglandin E₂ (PGE₂), tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and interleukin-6 (IL-6) as inflammatory parameters. We also examined the effect of VBME on intracellular reactive oxygen species (ROS) production and the activity of nuclear factor-kappa B p65 (NF-κB p65). VBME significantly inhibited LPS-induced production of NO and PGE2 and LPS-mediated upregulation of iNOS and COX-2 expression in a dose-dependent manner; importantly, VBME was not cytotoxic. VBME also significantly reduced the generation of the pro-inflammatory cytokines TNF-α, IL-1β, and IL-6. In addition, VBME significantly dampened intracellular ROS production and suppressed NF-κB p65 translocation by blocking IκB-α phosphorylation and degradation in LPS-stimulated BV2 cells. Our findings indicate that VBME inhibits the production of inflammatory mediators in BV-2 microglial cells by suppressing NF-κB signaling. Thus, VBME may be useful in the treatment of neurodegenerative diseases due to its ability to inhibit inflammatory mediator production in activated BV-2 microglial cells.

  15. Vaccinium bracteatum Thunb. Exerts Anti-Inflammatory Activity by Inhibiting NF-?B Activation in BV-2 Microglial Cells

    Kwon, Seung-Hwan; Ma, Shi-Xun; Ko, Yong-Hyun; Seo, Jee-Yeon; Lee, Bo-Ram; Lee, Taek Hwan; Kim, Sun Yeou; Lee, Seok-Yong; Jang, Choon-Gon

    2016-01-01

    This study was designed to evaluate the pharmacological effects of Vaccinium bracteatum Thunb. methanol extract (VBME) on microglial activation and to identify the underlying mechanisms of action of these effects. The anti-inflammatory properties of VBME were studied using lipopolysaccharide (LPS)-stimulated BV-2 microglial cells. We measured the production of nitric oxide (NO), inducible NO synthase (iNOS), cyclooxygenase (COX)-2, prostaglandin E2 (PGE2), tumor necrosis factor-alpha (TNF-?),...

  16. Scoparone exerts anti-tumor activity against DU145 prostate cancer cells via inhibition of STAT3 activity.

    Jeong-Kook Kim

    Full Text Available Scoparone, a natural compound isolated from Artemisia capillaris, has been used in Chinese herbal medicine to treat neonatal jaundice. Signal transducer and activator of transcription 3 (STAT3 contributes to the growth and survival of many human tumors. This study was undertaken to investigate the anti-tumor activity of scoparone against DU145 prostate cancer cells and to determine whether its effects are mediated by inhibition of STAT3 activity. Scoparone inhibited proliferation of DU145 cells via cell cycle arrest in G1 phase. Transient transfection assays showed that scoparone repressed both constitutive and IL-6-induced transcriptional activity of STAT3. Western blot and quantitative real-time PCR analyses demonstrated that scoparone suppressed the transcription of STAT3 target genes such as cyclin D1, c-Myc, survivin, Bcl-2, and Socs3. Consistent with this, scoparone decreased phosphorylation and nuclear accumulation of STAT3, but did not reduce phosphorylation of janus kinase 2 (JAK2 or Src, the major upstream kinases responsible for STAT3 activation. Moreover, transcriptional activity of a constitutively active mutant of STAT3 (STAT3C was inhibited by scoparone, but not by AG490, a JAK2 inhibitor. Furthermore, scoparone treatment suppressed anchorage-independent growth in soft agar and tumor growth of DU145 xenografts in nude mice, concomitant with a reduction in STAT3 phosphorylation. Computational modeling suggested that scoparone might bind the SH2 domain of STAT3. Our findings suggest that scoparone elicits an anti-tumor effect against DU145 prostate cancer cells in part through inhibition of STAT3 activity.

  17. EGb 761 Protects Cardiac Microvascular Endothelial Cells against Hypoxia/Reoxygenation Injury and Exerts Inhibitory Effect on the ATM Pathway.

    Zhang, Chao; Wang, Deng-Feng; Zhang, Zhuang; Han, Dong; Yang, Kan

    2017-03-28

    Ginkgo bilob a extract (EGb 761) has been widely used clinically to reduce myocardial ischemia reperfusion injury (MIRI). Microvascular endothelial cells (MVECs) may be a proper cellular model in vitro for the effect and mechanism study against MIRI. However, the protective effect of EGb 761 on MVECs resisting hypoxia/reoxygenation (H/R) injury is little reported. In this study, H/R-injured MVECs were treated with EGb 761, and then the cell viability, apoptosis, ROS production, SOD activity, caspase-3 activity, and protein level of ATM, γ-H2AX, p53, and Bax were measured. ATM siRNA was transfected to study the changes of protein in the ATM pathway. EGb 761 presented protective effect on H/R-injured MVECs, with decreasing cell death, apoptosis, and ROS, and elevated SOD activity. Next, EGb 761 could inhibit H/R-induced ATM, γ-H2AX, p53, and Bax in a dose-dependent manner. Moreover, ATM siRNA also could inhibit H/R-induced ATM, γ-H2AX, p53, and Bax. Overall, these findings verify that EGb 761 protects cardiac MVECs from H/R injury, and for the first time, illustrate the influence on the ATM pathway and apoptosis by EGb 761 via dampening ROS.

  18. [Pt(O,O'-acac)(gamma-acac)(DMS)], a new Pt compound exerting fast cytotoxicity in MCF-7 breast cancer cells via the mitochondrial apoptotic pathway.

    Muscella, A; Calabriso, N; Fanizzi, F P; De Pascali, S A; Urso, L; Ciccarese, A; Migoni, D; Marsigliante, S

    2008-01-01

    We showed previously that a new Pt complex containing an O,O'-chelated acetylacetonate ligand (acac) and a dimethylsulphide in the Pt coordination sphere, [Pt(O,O'-acac)(gamma-acac)(DMS)], induces apoptosis in HeLa cells. The objective of this study was to investigate the hypothesis that [Pt(O,O'-acac)(gamma-acac)(DMS)] is also cytotoxic in a MCF-7 breast cancer cell line relatively insensitive to cisplatin, and to gain a more detailed analysis of the cell death pathways. Cells were treated with Pt compounds and cytotoxicity tests were performed, together with Western blotting of various proteins involved in apoptosis. The mitochondrial membrane potential was assessed by fluorescence microscopy and spectrofluorometry and the Pt bound to cell fractions was measured by atomic absorption spectrometry. In contrast to cisplatin, the cytotoxicity of [Pt(O,O'-acac)(gamma-acac)(DMS)] correlated with cellular accumulation but not with DNA binding. Also, the Pt content in DNA bases was considerably higher for cisplatin than for [Pt(O,O'-acac)(gamma-acac)(DMS)], thus excluding DNA as a target of [Pt(O,O'-acac)(gamma-acac)(DMS)]. [Pt(O,O'-acac)(gamma-acac)(DMS)] exerted high and fast apoptotic processes in MCF-7 cells since it provoked: (a) mitochondria depolarization; (b) cytochrome c accumulation in the cytosol; (c) translocation of Bax and truncated-Bid from cytosol to mitochondria and decreased expression of Bcl-2; (d) cleavage of caspases -7 and -9, and PARP degradation; (e) chromatin condensation and DNA fragmentation. [Pt(O,O'-acac)(gamma-acac)(DMS)] is highly cytotoxic for MCF-7 cells, cells relatively resistant to many chemotherapeutic agents, as it activates the mitochondrial apoptotic pathway. Hence, [Pt(O,O'-acac)(gamma-acac)(DMS)] has the potential to provide us with new opportunities for therapeutic intervention.

  19. Perspectives on Exertional Rhabdomyolysis.

    Rawson, Eric S; Clarkson, Priscilla M; Tarnopolsky, Mark A

    2017-03-01

    Exertional (exercise-induced) rhabdomyolysis is a potentially life threatening condition that has been the subject of research, intense discussion, and media attention. The causes of rhabdomyolysis are numerous and can include direct muscle injury, unaccustomed exercise, ischemia, extreme temperatures, electrolyte abnormalities, endocrinologic conditions, genetic disorders, autoimmune disorders, infections, drugs, toxins, and venoms. The objective of this article is to review the literature on exertional rhabdomyolysis, identify precipitating factors, and examine the role of the dietary supplement creatine monohydrate. PubMed and SPORTDiscus databases were searched using the terms rhabdomyolysis, muscle damage, creatine, creatine supplementation, creatine monohydrate, and phosphocreatine. Additionally, the references of papers identified through this search were examined for relevant studies. A meta-analysis was not performed. Although the prevalence of rhabdomyolysis is low, instances still occur where exercise is improperly prescribed or used as punishment, or incomplete medical history is taken, and exertional rhabdomyolysis occurs. Creatine monohydrate does not appear to be a precipitating factor for exertional rhabdomyolysis. Healthcare professionals should be able to recognize the basic signs of exertional rhabdomyolysis so prompt treatment can be administered. For the risk of rhabdomyolysis to remain low, exercise testing and prescription must be properly conducted based on professional standards.

  20. Bitter melon juice exerts its efficacy against pancreatic cancer via targeting both bulk and cancer stem cells.

    Dhar, Deepanshi; Deep, Gagan; Kumar, Sushil; Wempe, Michael F; Raina, Komal; Agarwal, Chapla; Agarwal, Rajesh

    2018-05-04

    Pancreatic cancer (PanC) is one of the deadliest malignancies worldwide and frontline treatment with gemcitabine becomes eventually ineffective due to increasing PanC resistance, suggesting additional approaches are needed to manage PanC. Recently, we have shown the efficacy of bitter melon juice (BMJ) against PanC cells, including those resistant to gemcitabine. Since cancer stem cells (CSCs) are actively involved in PanC initiation, progression, relapse and drug-resistance, here we assessed BMJ ability in targeting pancreatic cancer-associated cancer stem cells (PanC-CSCs). We found BMJ efficacy against CD44 + /CD24 + /EpCAM high enriched PanC-CSCs in spheroid assays; BMJ also increased the sensitivity of gemcitabine-resistant PanC-CSCs. Exogenous addition of BMJ to PanC-CSC generated spheroids (not pre-exposed to BMJ) also significantly reduced spheroid number and size. Mechanistically, BMJ effects were associated with a decrease in the expression of genes and proteins involved in PanC-CSC renewal and proliferation. Specifically, immunofluorescence staining showed that BMJ decreases protein expression/nuclear localization of CSC-associated transcription factors SOX2, OCT4 and NANOG, and CSC marker CD44. Immunohistochemical analysis of MiaPaCa2 xenografts from BMJ treated animals also showed a significant decrease in the levels of CSC-associated transcription factors. Together, these results show BMJ potential in targeting PanC-CSC pool and associated regulatory pathways, suggesting the need for further investigation of its efficacy against PanC growth and progression including gemcitabine-resistant PanC. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  1. Artesunate Exerts a Direct Effect on Endothelial Cell Activation and NF-κB Translocation in a Mechanism Independent of Plasmodium Killing

    Mariana C. Souza

    2012-01-01

    Full Text Available Artemisinin and its derivates are an important class of antimalarial drug and are described to possess immunomodulatory activities. Few studies have addressed the effect of artesunate in the murine malaria model or its effect on host immune response during malaria infection. Herein, we study the effect of artesunate treatment and describe an auxiliary mechanism of artesunate in modulating the inflammatory response during experimental malaria infection in mice. Treatment with artesunate did not reduce significantly the parasitemia within 12 h, however, reduced BBB breakdown and TNF-α mRNA expression in the brain tissue of artesunate-treated mice. Conversely, mefloquine treatment was not able to alter clinical features. Notably, artesunate pretreatment failed to modulate the expression of LFA-1 in splenocytes stimulated with parasitized red blood cells (pRBCs in vitro; however, it abrogated the expression of ICAM-1 in pRBC-stimulated endothelial cells. Accordingly, a cytoadherence in vitro assay demonstrated that pRBCs did not adhere to artesunate-treated vascular endothelial cells. In addition, NF-κB nuclear translocation in endothelial cells stimulated with pRBCs was impaired by artesunate treatment. Our results suggest that artesunate is able to exert a protective effect against the P. berghei-induced inflammatory response by inhibiting NF-κB nuclear translocation and the subsequent expression of ICAM-1.

  2. Vitamins K2, K3 and K5 exert antitumor effects on established colorectal cancer in mice by inducing apoptotic death of tumor cells.

    Ogawa, Mutsumi; Nakai, Seiji; Deguchi, Akihiro; Nonomura, Takako; Masaki, Tsutomu; Uchida, Naohito; Yoshiji, Hitoshi; Kuriyama, Shigeki

    2007-08-01

    Although a number of studies have shown that vitamin K possesses antitumor activities on various neoplastic cell lines, there are few reports demonstrating in vivo antitumor effects of vitamin K, and the antitumor effect on colorectal cancer (CRC) remains to be examined. Therefore, antitumor effects of vitamin K on CRC were examined both in vitro and in vivo. Vitamins K2, K3 and K5 suppressed the proliferation of colon 26 cells in a dose-dependent manner, while vitamin K1 did not. On flow cytometry, induction of apoptosis by vitamins K2, K3 and K5 was suggested by population in sub-G1 phase of the cell cycle. Hoechst 33342 staining and a two-color flow cytometric assay using fluorescein isothiocyanate-conjugated annexin V and propidium iodide confirmed that vitamins K2, K3 and K5 induced apoptotic death of colon 26 cells. Enzymatic activity of caspase-3 in colon 26 cells was significantly up-regulated by vitamins K2, K3 and K5. The pan-caspase inhibitor, benzyloxycarbonyl-Val-Ala-Asp-fluoromethyl ketone, substantially prevented vitamin K-mediated apoptosis. In vivo study using syngeneic mice with subcutaneously established colon 26 tumors demonstrated that intravenous administration of vitamins K2, K3 and K5 significantly suppressed the tumor growth. The number of apoptotic tumor cells was significantly larger in the vitamin K-treated groups than in the control group. These results suggest that vitamins K2, K3 and K5 exerted effective antitumor effects on CRC in vitro and in vivo by inducing caspase-dependent apoptotic death of tumor cells, suggesting that these K vitamins may be promising agents for the treatment of patients with CRC.

  3. Sevoflurane improves gaseous exchange and exerts protective ...

    Sevoflurane improves gaseous exchange and exerts protective effects in ... Lung water content and cell count were estimated by standard protocols. ... It reversed LPS-induced oxidative stress, as demonstrated by increase in total antioxidant ...

  4. Lactobacillus casei Exerts Anti-Proliferative Effects Accompanied by Apoptotic Cell Death and Up-Regulation of TRAIL in Colon Carcinoma Cells

    Tiptiri-Kourpeti, Angeliki; Spyridopoulou, Katerina; Santarmaki, Valentina; Aindelis, Georgios; Tompoulidou, Evgenia; Lamprianidou, Eleftheria E.; Saxami, Georgia; Ypsilantis, Petros; Lampri, Evangeli S.; Simopoulos, Constantinos; Kotsianidis, Ioannis; Galanis, Alex; Kourkoutas, Yiannis; Dimitrellou, Dimitra; Chlichlia, Katerina

    2016-01-01

    Probiotic microorganisms such as lactic acid bacteria (LAB) exert a number of strain-specific health-promoting activities attributed to their immunomodulatory, anti-inflammatory and anti-carcinogenic properties. Despite recent attention, our understanding of the biological processes involved in the beneficial effects of LAB strains is still limited. To this end, the present study investigated the growth-inhibitory effects of Lactobacillus casei ATCC 393 against experimental colon cancer. Admi...

  5. 3-dimensional analysis of FELIX brick with hole

    Lee, Taek-Kyung; Lee, Soo-Young; Ra, Jung-Woong

    1987-01-01

    Electromagnetic induction on FELIX brick with a hole has been analyzed with 3-Dimensional EDDYNET computer code. Incorporating loop currents on hexahedral meshes, the 3-Dimensional EDDYNET program solves eddy current problems by a network approach, and provides good accuracy even for coarse meshes. (author)

  6. Hyperglycemia and oxidized-LDL exert a deleterious effect on endothelial progenitor cell migration in type 2 diabetes mellitus.

    Hamed, Saher; Brenner, Benjamin; Abassi, Zaid; Aharon, Anat; Daoud, Deeb; Roguin, Ariel

    2010-09-01

    Type 2 diabetes mellitus (DM) patients with coronary artery disease (CAD) have elevated plasma oxidized-LDL (OxLDL) levels and impaired neovascularization. Hyperglycemia and hyperlipidemia impair endothelial progenitor cell (EPC) migration, and endothelial nitric oxide (NO) bioavailability and NO synthase (NOS) activity are essential for EPC migration. Stromal-derived factor-1alpha (SDF1alpha) contributes to EPC mobilization and homing by stimulating the CXC receptor-4 (CXCR4) on the EPC plasmalemma to activate the Pi3K/Akt/eNOS signaling pathway. Therefore, we investigated the effect of high glucose (HG) and OxLDL on the migration and NO bioavailability of EPCs from healthy individuals, and then correlated the findings with those of EPCs from type 2 DM patients with and without CAD. EPCs from 15 healthy and 55 patients were exposed to HG, OxLDL, or both before evaluating EPC count, migration and NO production, and expression of CXCR4 and members of Pi3K/Akt/eNOS signaling cascade. Counts, migration, CXCR4 expression, and NO production were significantly reduced in EPCs from DM and CAD patients compared with that obtained in EPCs from healthy, and were further reduced in DM patients with CAD. The expression of CXCR4 and activation of Pi3K/Akt/eNOS signaling cascade were suppressed in OxLDL- and HG-treated EPCs, and this suppression was exacerbated when EPCs were treated simultaneously with HG and OxLDL. Hyperglycemia and elevated circulating OxLDL in DM patients with CAD severely impair EPC migration. These results suggest that the underlying mechanism for this impaired EPC migration is linked to the CXCR4/Pi3K/Akt/eNOS signaling pathway. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

  7. Ebselen exerts antifungal activity by regulating glutathione (GSH) and reactive oxygen species (ROS) production in fungal cells.

    Thangamani, Shankar; Eldesouky, Hassan E; Mohammad, Haroon; Pascuzzi, Pete E; Avramova, Larisa; Hazbun, Tony R; Seleem, Mohamed N

    2017-01-01

    Ebselen, an organoselenium compound and a clinically safe molecule has been reported to possess potent antifungal activity, but its antifungal mechanism of action and in vivo antifungal activity remain unclear. The antifungal effect of ebselen was tested against Candida albicans, C. glabrata, C. tropicalis, C. parapsilosis, Cryptococcus neoformans, and C. gattii clinical isolates. Chemogenomic profiling and biochemical assays were employed to identify the antifungal target of ebselen. Ebselen's antifungal activity in vivo was investigated in a Caenorhabditis elegans animal model. Ebselen exhibits potent antifungal activity against both Candida spp. and Cryptococcus spp., at concentrations ranging from 0.5 to 2μg/ml. Ebselen rapidly eradicates a high fungal inoculum within 2h of treatment. Investigation of the drug's antifungal mechanism of action indicates that ebselen depletes intracellular glutathione (GSH) levels, leading to increased production of reactive oxygen species (ROS), and thereby disturbs the redox homeostasis in fungal cells. Examination of ebselen's in vivo antifungal activity in two Caenorhabditis elegans models of infection demonstrate that ebselen is superior to conventional antifungal drugs (fluconazole, flucytosine and amphotericin) in reducing Candida and Cryptococcus fungal load. Ebselen possesses potent antifungal activity against clinically relevant isolates of both Candida and Cryptococcus by regulating GSH and ROS production. The potent in vivo antifungal activity of ebselen supports further investigation for repurposing it for use as an antifungal agent. The present study shows that ebselen targets glutathione and also support that glutathione as a potential target for antifungal drug development. Copyright © 2016 Elsevier B.V. All rights reserved.

  8. LUBAC-Recruited CYLD and A20 Regulate Gene Activation and Cell Death by Exerting Opposing Effects on Linear Ubiquitin in Signaling Complexes

    Peter Draber

    2015-12-01

    Full Text Available Ubiquitination and deubiquitination are crucial for assembly and disassembly of signaling complexes. LUBAC-generated linear (M1 ubiquitin is important for signaling via various immune receptors. We show here that the deubiquitinases CYLD and A20, but not OTULIN, are recruited to the TNFR1- and NOD2-associated signaling complexes (TNF-RSC and NOD2-SC, at which they cooperate to limit gene activation. Whereas CYLD recruitment depends on its interaction with LUBAC, but not on LUBAC’s M1-chain-forming capacity, A20 recruitment requires this activity. Intriguingly, CYLD and A20 exert opposing effects on M1 chain stability in the TNF-RSC and NOD2-SC. While CYLD cleaves M1 chains, and thereby sensitizes cells to TNF-induced death, A20 binding to them prevents their removal and, consequently, inhibits cell death. Thus, CYLD and A20 cooperatively restrict gene activation and regulate cell death via their respective activities on M1 chains. Hence, the interplay between LUBAC, M1-ubiquitin, CYLD, and A20 is central for physiological signaling through innate immune receptors.

  9. Curcumin and trans-resveratrol exert cell cycle-dependent radioprotective or radiosensitizing effects as elucidated by the PCC and G2-assay

    Sebastià, N., E-mail: natividad.sebastia@uv.es [Radiation Protection Service, IIS La Fe, Health Research Institute La Fe, Valencia (Spain); Montoro, A. [Radiation Protection Service, Universitary and Politechnic Hospital La Fe, Valencia (Spain); Grupo de Investigación Biomédica en Imagen GIBI230, IIS La Fe, Health Research Institute La Fe, Valencia (Spain); Unidad Mixta de Investigación en Endocrinología, Nutrición y Dietética Clínica, IIS La Fe, Health Research Institute La Fe, Valencia (Spain); Hervás, D. [Biostatistics Unit, IIS La Fe, Health Research Institute La Fe, Valencia (Spain); Pantelias, G.; Hatzi, V.I. [Institute of Nuclear and Radiological Sciences and Technology, Energy and Safety, National Centre for Scientific Research “Demokritos”, Aghia Paraskevi, Athens (Greece); Soriano, J.M. [Grupo de Investigación Biomédica en Imagen GIBI230, IIS La Fe, Health Research Institute La Fe, Valencia (Spain); Unidad Mixta de Investigación en Endocrinología, Nutrición y Dietética Clínica, IIS La Fe, Health Research Institute La Fe, Valencia (Spain); Department of Preventive Medicine and Public Health, Faculty of Pharmacy, University of Valencia, Burjassot, Valencia (Spain); Villaescusa, J.I. [Radiation Protection Service, Universitary and Politechnic Hospital La Fe, Valencia (Spain); and others

    2014-08-15

    Highlights: • Curcumin and trans-resveratrol can exert radioprotective or radiosensitizing effects. • The mechanisms underlying such dual action were elucidated using the PCC and G2-assay. • Radioprotection occurs in non-cycling cells exposed to curcumin and resveratrol. • Radiosensitization occurs in cycling cells exposed to the chemicals. • G2-checkpoint abrogation by the chemicals underlies the radiosensitizing mechanism. - Abstract: Curcumin and trans-resveratrol are well-known antioxidant polyphenols with radiomodulatory properties, radioprotecting non-cancerous cells while radiosensitizing tumor cells. This dual action may be the result of their radical scavenging properties and their effects on cell-cycle checkpoints that are activated in response to radiation-induced chromosomal damage. It could be also caused by their effect on regulatory pathways with impact on detoxification enzymes, the up-regulation of endogenous protective systems, and cell-cycle-dependent processes of DNA damage. This work aims to elucidate the mechanisms underlying the dual action of these polyphenols and investigates under which conditions they exhibit radioprotecting or radiosensitizing properties. The peripheral blood lymphocyte test system was used, applying concentrations ranging from 1.4 to 140 μM curcumin and 2.2 to 220 μM trans-resveratrol. The experimental design focuses first on their radioprotective effects in non-cycling lymphocytes, as uniquely visualized using cell fusion-mediated premature chromosome condensation, excluding, thus, cell-cycle interference to repair processes and activation of checkpoints. Second, the radiosensitizing potential of these chemicals on the induction of chromatid breaks in cultured lymphocytes following G2-phase irradiation was evaluated by a standardized G2-chromosomal radiosensitivity predictive assay. This assay uses caffeine for G2-checkpoint abrogation and it was applied to obtain an internal control for radiosensitivity

  10. Curcumin and trans-resveratrol exert cell cycle-dependent radioprotective or radiosensitizing effects as elucidated by the PCC and G2-assay

    Sebastià, N.; Montoro, A.; Hervás, D.; Pantelias, G.; Hatzi, V.I.; Soriano, J.M.; Villaescusa, J.I.

    2014-01-01

    Highlights: • Curcumin and trans-resveratrol can exert radioprotective or radiosensitizing effects. • The mechanisms underlying such dual action were elucidated using the PCC and G2-assay. • Radioprotection occurs in non-cycling cells exposed to curcumin and resveratrol. • Radiosensitization occurs in cycling cells exposed to the chemicals. • G2-checkpoint abrogation by the chemicals underlies the radiosensitizing mechanism. - Abstract: Curcumin and trans-resveratrol are well-known antioxidant polyphenols with radiomodulatory properties, radioprotecting non-cancerous cells while radiosensitizing tumor cells. This dual action may be the result of their radical scavenging properties and their effects on cell-cycle checkpoints that are activated in response to radiation-induced chromosomal damage. It could be also caused by their effect on regulatory pathways with impact on detoxification enzymes, the up-regulation of endogenous protective systems, and cell-cycle-dependent processes of DNA damage. This work aims to elucidate the mechanisms underlying the dual action of these polyphenols and investigates under which conditions they exhibit radioprotecting or radiosensitizing properties. The peripheral blood lymphocyte test system was used, applying concentrations ranging from 1.4 to 140 μM curcumin and 2.2 to 220 μM trans-resveratrol. The experimental design focuses first on their radioprotective effects in non-cycling lymphocytes, as uniquely visualized using cell fusion-mediated premature chromosome condensation, excluding, thus, cell-cycle interference to repair processes and activation of checkpoints. Second, the radiosensitizing potential of these chemicals on the induction of chromatid breaks in cultured lymphocytes following G2-phase irradiation was evaluated by a standardized G2-chromosomal radiosensitivity predictive assay. This assay uses caffeine for G2-checkpoint abrogation and it was applied to obtain an internal control for radiosensitivity

  11. Exertional dyspnoea in obesity

    Vipa Bernhardt

    2016-12-01

    Full Text Available The purpose of cardiopulmonary exercise testing (CPET in the obese person, as in any cardiopulmonary exercise test, is to determine the patient's exercise tolerance, and to help identify and/or distinguish between the various physiological factors that could contribute to exercise intolerance. Unexplained dyspnoea on exertion is a common reason for CPET, but it is an extremely complex symptom to explain. Sometimes obesity is the simple answer by elimination of other possibilities. Thus, distinguishing among multiple clinical causes for exertional dyspnoea depends on the ability to eliminate possibilities while recognising response patterns that are unique to the obese patient. This includes the otherwise healthy obese patient, as well as the obese patient with potentially multiple cardiopulmonary limitations. Despite obvious limitations in lung function, metabolic disease and/or cardiovascular dysfunction, obesity may be the most likely reason for exertional dyspnoea. In this article, we will review the more common cardiopulmonary responses to exercise in the otherwise healthy obese adult with special emphasis on dyspnoea on exertion.

  12. NF-κB functions as a molecular link between tumor cells and Th1/Tc1 T cells in the tumor microenvironment to exert radiation-mediated tumor suppression

    Simon, Priscilla S.; Bardhan, Kankana; Chen, May R.; Paschall, Amy V.; Lu, Chunwan; Bollag, Roni J.; Kong, Feng-Chong; Jin, JianYue; Kong, Feng-Ming; Waller, Jennifer L.; Pollock, Raphael E.; Liu, Kebin

    2016-01-01

    Radiation modulates both tumor cells and immune cells in the tumor microenvironment to exert its anti-tumor activity; however, the molecular connection between tumor cells and immune cells that mediates radiation-exerted tumor suppression activity in the tumor microenvironment is largely unknown. We report here that radiation induces rapid activation of the p65/p50 and p50/p50 NF-κB complexes in human soft tissue sarcoma (STS) cells. Radiation-activated p65/p50 and p50/p50 bind to the TNFα promoter to activate its transcription in STS cells. Radiation-induced TNFα induces tumor cell death in an autocrine manner. A sublethal dose of Smac mimetic BV6 induces cIAP1 and cIAP2 degradation to increase tumor cell sensitivity to radiation-induced cell death in vitro and to enhance radiation-mediated suppression of STS xenografts in vivo. Inhibition of caspases, RIP1, or RIP3 blocks radiation/TNFα-induced cell death, whereas inhibition of RIP1 blocks TNFα-induced caspase activation, suggesting that caspases and RIP1 act sequentially to mediate the non-compensatory cell death pathways. Furthermore, we determined in a syngeneic sarcoma mouse model that radiation up-regulates IRF3, IFNβ, and the T cell chemokines CCL2 and CCL5 in the tumor microenvironment, which are associated with activation and increased infiltration of Th1/Tc1 T cells in the tumor microenvironment. Moreover, tumor-infiltrating T cells are in their active form since both the perforin and FasL pathways are activated in irradiated tumor tissues. Consequently, combined BV6 and radiation completely suppressed tumor growth in vivo. Therefore, radiation-induced NF-κB functions as a molecular link between tumor cells and immune cells in the tumor microenvironment for radiation-mediated tumor suppression. PMID:27014915

  13. Fucoxanthin exerts differing effects on 3T3-L1 cells according to differentiation stage and inhibits glucose uptake in mature adipocytes

    Kang, Seong-Il; Ko, Hee-Chul; Shin, Hye-Sun; Kim, Hyo-Min; Hong, Youn-Suk; Lee, Nam-Ho; Kim, Se-Jae

    2011-01-01

    Highlights: → Fucoxanthin enhances 3T3-L1 adipocyte differentiation at an early stage. → Fucoxanthin inhibits 3T3-L1 adipocyte differentiation at intermediate and late stages. → Fucoxanthin attenuates glucose uptake by inhibiting the phosphorylation of IRS in mature 3T3-L1 adipocytes. → Fucoxanthin exerts its anti-obesity effect by inhibiting the differentiation of adipocytes at both intermediate and late stages, as well as glucose uptake in mature adipocytes. -- Abstract: Progression of 3T3-L1 preadipocyte differentiation is divided into early (days 0-2, D0-D2), intermediate (days 2-4, D2-D4), and late stages (day 4 onwards, D4-). In this study, we investigated the effects of fucoxanthin, isolated from the edible brown seaweed Petalonia binghamiae, on adipogenesis during the three differentiation stages of 3T3-L1 preadipocytes. When fucoxanthin was applied during the early stage of differentiation (D0-D2), it promoted 3T3-L1 adipocyte differentiation, as evidenced by increased triglyceride accumulation. At the molecular level, fucoxanthin increased protein expression of peroxisome proliferator-activated receptor γ (PPARγ), CCAAT/enhancer-binding protein α (C/EBPα), sterol regulatory element-binding protein 1c (SREBP1c), and aP2, and adiponectin mRNA expression, in a dose-dependent manner. However, it reduced the expression of PPARγ, C/EBPα, and SREBP1c during the intermediate (D2-D4) and late stages (D4-D7) of differentiation. It also inhibited the uptake of glucose in mature 3T3-L1 adipocytes by reducing the phosphorylation of insulin receptor substrate 1 (IRS-1). These results suggest that fucoxanthin exerts differing effects on 3T3-L1 cells of different differentiation stages and inhibits glucose uptake in mature adipocytes.

  14. Telmisartan Exerts Anti-Tumor Effects by Activating Peroxisome Proliferator-Activated Receptor-γ in Human Lung Adenocarcinoma A549 Cells

    Juan Li

    2014-03-01

    Full Text Available Telmisartan, a member of the angiotensin II type 1 receptor blockers, is usually used for cardiovascular diseases. Recent studies have showed that telmisartan has the property of PPARγ activation. Meanwhile, PPARγ is essential for tumor proliferation, invasion and metastasis. In this work we explore whether telmisartan could exert anti-tumor effects through PPARγ activation in A549 cells. MTT and trypan blue exclusion assays were included to determine the survival rates and cell viabilities. RT-PCR and western blotting were used to analyze the expression of ICAM-1, MMP-9 and PPARγ. DNA binding activity of PPARγ was evaluated by EMSA. Our data showed that the survival rates and cell viabilities of A549 cells were all reduced by telmisartan in a time- and concentration-dependent manner. Meanwhile, our results also demonstrated that telmisartan dose-dependently inhibited the expression of ICAM-1 and MMP-9. Moreover, the cytotoxic and anti-proliferative effects, ICAM-1 and MMP-9 inhibitive properties of telmisartan were totally blunted by the PPARγ antagonist GW9662. Our findings also showed that the expression of PPARγ was up-regulated by telmisartan in a dose dependent manner. And, the EMSA results also figured out that DNA binding activity of PPARγ was dose-dependently increased by telmisartan. Additionally, our data also revealed that telmisartan-induced PPARγ activation was abrogated by GW9662. Taken together, our results indicated that telmisartan inhibited the expression of ICAM-1 and MMP-9 in A549 cells, very likely through the up-regulation of PPARγ synthesis.

  15. Fatty Acids Dietary Supplements Exert Anti-Inflammatory Action and Limit Ganglion Cell Degeneration in the Retina of the EAE Mouse Model of Multiple Sclerosis

    Locri, Filippo; Amato, Rosario; Marsili, Stefania; Rusciano, Dario; Bagnoli, Paola

    2018-01-01

    Optic neuritis is an acute inflammatory demyelinating disorder of the optic nerve (ON) and is an initial symptom of multiple sclerosis (MS). Optic neuritis is characterized by ON degeneration and retinal ganglion cell (RGC) loss that contributes to permanent visual disability and lacks a reliable treatment. Here, we used the experimental autoimmune encephalomyelitis (EAE) mouse model of MS, a well-established model also for optic neuritis. In this model, C57BL6 mice, intraperitoneally injected with a fragment of the myelin oligodendrocyte glycoprotein (MOG), were found to develop inflammation, Müller cell gliosis, and infiltration of macrophages with increased production of oncomodulin (OCM), a calcium binding protein that acts as an atypical trophic factor for neurons enabling RGC axon regeneration. Immunolabeling of retinal whole mounts with a Brn3a antibody demonstrated drastic RGC loss. Dietary supplementation with Neuro-FAG (nFAG®), a balanced mixture of fatty acids (FAs), counteracted inflammatory and gliotic processes in the retina. In contrast, infiltration of macrophages and their production of OCM remained at elevated levels thus eventually preserving OCM trophic activity. In addition, the diet supplement with nFAG exerted a neuroprotective effect preventing MOG-induced RGC death. In conclusion, these data suggest that the balanced mixture of FAs may represent a useful form of diet supplementation to limit inflammatory events and death of RGCs associated to optic neuritis. This would occur without affecting macrophage infiltration and the release of OCM thus favoring the maintenance of OCM neuroprotective role. PMID:29517994

  16. Fatty Acids Dietary Supplements Exert Anti-Inflammatory Action and Limit Ganglion Cell Degeneration in the Retina of the EAE Mouse Model of Multiple Sclerosis

    Massimo Dal Monte

    2018-03-01

    Full Text Available Optic neuritis is an acute inflammatory demyelinating disorder of the optic nerve (ON and is an initial symptom of multiple sclerosis (MS. Optic neuritis is characterized by ON degeneration and retinal ganglion cell (RGC loss that contributes to permanent visual disability and lacks a reliable treatment. Here, we used the experimental autoimmune encephalomyelitis (EAE mouse model of MS, a well-established model also for optic neuritis. In this model, C57BL6 mice, intraperitoneally injected with a fragment of the myelin oligodendrocyte glycoprotein (MOG, were found to develop inflammation, Müller cell gliosis, and infiltration of macrophages with increased production of oncomodulin (OCM, a calcium binding protein that acts as an atypical trophic factor for neurons enabling RGC axon regeneration. Immunolabeling of retinal whole mounts with a Brn3a antibody demonstrated drastic RGC loss. Dietary supplementation with Neuro-FAG (nFAG®, a balanced mixture of fatty acids (FAs, counteracted inflammatory and gliotic processes in the retina. In contrast, infiltration of macrophages and their production of OCM remained at elevated levels thus eventually preserving OCM trophic activity. In addition, the diet supplement with nFAG exerted a neuroprotective effect preventing MOG-induced RGC death. In conclusion, these data suggest that the balanced mixture of FAs may represent a useful form of diet supplementation to limit inflammatory events and death of RGCs associated to optic neuritis. This would occur without affecting macrophage infiltration and the release of OCM thus favoring the maintenance of OCM neuroprotective role.

  17. Exertional Rhabdomyolysis after Spinning.

    Jeong, Youjin; Kweon, Hyuk-Jung; Oh, Eun-Jung; Ahn, Ah-Leum; Choi, Jae-Kyung; Cho, Dong-Yung

    2016-11-01

    Any strenuous muscular exercise may trigger rhabdomyolysis. We report an episode of clinically manifested exertional rhabdomyolysis due to stationary cycling, commonly known as spinning. Reports of spinning-related rhabdomyolysis are rare in the English literature, and the current case appears to be the first such case reported in South Korea. A previously healthy 21-year-old Asian woman presented with severe thigh pain and reddish-brown urinary discoloration 24-48 hours after attending a spinning class at a local gymnasium. Paired with key laboratory findings, her symptoms were suggestive of rhabdomyolysis. She required hospital admission to sustain renal function through fluid resuscitation therapy and fluid balance monitoring. Because exertional rhabdomyolysis may occur in any unfit but otherwise healthy individual who indulges in stationary cycling, the potential health risks of this activity must be considered.

  18. Exertional Rhabdomyolysis after Spinning

    Jeong, Youjin; Kweon, Hyuk-Jung; Oh, Eun-Jung; Ahn, Ah-Leum; Choi, Jae-Kyung; Cho, Dong-Yung

    2016-01-01

    Any strenuous muscular exercise may trigger rhabdomyolysis. We report an episode of clinically manifested exertional rhabdomyolysis due to stationary cycling, commonly known as spinning. Reports of spinning-related rhabdomyolysis are rare in the English literature, and the current case appears to be the first such case reported in South Korea. A previously healthy 21-year-old Asian woman presented with severe thigh pain and reddish-brown urinary discoloration 24?48 hours after attending a spi...

  19. Electrochemically reduced water exerts superior reactive oxygen species scavenging activity in HT1080 cells than the equivalent level of hydrogen-dissolved water.

    Takeki Hamasaki

    Full Text Available Electrochemically reduced water (ERW is produced near a cathode during electrolysis and exhibits an alkaline pH, contains richly dissolved hydrogen, and contains a small amount of platinum nanoparticles. ERW has reactive oxygen species (ROS-scavenging activity and recent studies demonstrated that hydrogen-dissolved water exhibits ROS-scavenging activity. Thus, the antioxidative capacity of ERW is postulated to be dependent on the presence of hydrogen levels; however, there is no report verifying the role of dissolved hydrogen in ERW. In this report, we clarify whether the responsive factor for antioxidative activity in ERW is dissolved hydrogen. The intracellular ROS scavenging activity of ERW and hydrogen-dissolved water was tested by both fluorescent stain method and immuno spin trapping assay. We confirm that ERW possessed electrolysis intensity-dependent intracellular ROS-scavenging activity, and ERW exerts significantly superior ROS-scavenging activity in HT1080 cells than the equivalent level of hydrogen-dissolved water. ERW retained its ROS-scavenging activity after removal of dissolved hydrogen, but lost its activity when autoclaved. An oxygen radical absorbance capacity assay, the 2,2-diphenyl-1-picrylhydrazyl assay and chemiluminescence assay could not detect radical-scavenging activity in both ERW and hydrogen-dissolved water. These results indicate that ERW contains electrolysis-dependent hydrogen and an additional antioxidative factor predicted to be platinum nanoparticles.

  20. Interference with PSMB4 Expression Exerts an Anti-Tumor Effect by Decreasing the Invasion and Proliferation of Human Glioblastoma Cells

    Yu-Chen Cheng

    2018-01-01

    matrix metallopeptidase 9 in vivo. Conclusion: PSMB4 inhibition in combination with TMZ may exert an anti-tumor effect by decreasing cell proliferation and invasion as well as by promoting apoptosis in human glioblastoma cells. This research may improve the therapeutic efficacy of glioblastoma treatment.

  1. The potential of 3-dimensional construct engineered from poly(lactic-co-glycolic acid)/fibrin hybrid scaffold seeded with bone marrow mesenchymal stem cells for in vitro cartilage tissue engineering.

    Abdul Rahman, Rozlin; Mohamad Sukri, Norhamiza; Md Nazir, Noorhidayah; Ahmad Radzi, Muhammad Aa'zamuddin; Zulkifly, Ahmad Hafiz; Che Ahmad, Aminudin; Hashi, Abdurezak Abdulahi; Abdul Rahman, Suzanah; Sha'ban, Munirah

    2015-08-01

    Articular cartilage is well known for its simple uniqueness of avascular and aneural structure that has limited capacity to heal itself when injured. The use of three dimensional construct in tissue engineering holds great potential in regenerating cartilage defects. This study evaluated the in vitro cartilaginous tissue formation using rabbit's bone marrow mesenchymal stem cells (BMSCs)-seeded onto poly(lactic-co-glycolic acid) PLGA/fibrin and PLGA scaffolds. The in vitro cartilaginous engineered constructs were evaluated by gross inspection, histology, cell proliferation, gene expression and sulphated glycosaminoglycan (sGAG) production at week 1, 2 and 3. After 3 weeks of culture, the PLGA/fibrin construct demonstrated gross features similar to the native tissue with smooth, firm and glistening appearance, superior histoarchitectural and better cartilaginous extracellular matrix compound in concert with the positive glycosaminoglycan accumulation on Alcian blue. Significantly higher cell proliferation in PLGA/fibrin construct was noted at day-7, day-14 and day-21 (ptissue engineered cartilage. Copyright © 2015 Elsevier Ltd. All rights reserved.

  2. Molecular Signatures in the Prevention of Radiation Damage by the Synergistic Effect of N-Acetyl Cysteine and Qingre Liyan Decoction, a Traditional Chinese Medicine, Using a 3-Dimensional Cell Culture Model of Oral Mucositis

    Maria P. Lambros

    2015-01-01

    Full Text Available Qingre Liyan decoction (QYD, a Traditional Chinese medicine, and N-acetyl cysteine (NAC have been used to prevent radiation induced mucositis. This work evaluates the protective mechanisms of QYD, NAC, and their combination (NAC-QYD at the cellular and transcriptional level. A validated organotypic model of oral mucosal consisting of a three-dimensional (3D cell tissue-culture of primary human keratinocytes exposed to X-ray irradiation was used. Six hours after the irradiation, the tissues were evaluated by hematoxylin and eosin (H and E and a TUNEL assay to assess histopathology and apoptosis, respectively. Total RNA was extracted and used for microarray gene expression profiling. The tissue-cultures treated with NAC-QYD preserved their integrity and showed no apoptosis. Microarray results revealed that the NAC-QYD caused the upregulation of genes encoding metallothioneins, HMOX1, and other components of the Nrf2 pathway, which protects against oxidative stress. DNA repair genes (XCP, GADD45G, RAD9, and XRCC1, protective genes (EGFR and PPARD, and genes of the NFκB pathway were upregulated. Finally, tissue-cultures treated prophylactically with NAC-QYD showed significant downregulation of apoptosis, cytokines and chemokines genes, and constrained damage-associated molecular patterns (DAMPs. NAC-QYD treatment involves the protective effect of Nrf2, NFκB, and DNA repair factors.

  3. Deoxycholic acid and selenium metabolite methylselenol exert common and distinct effects on cell cycle, apoptosis, and MAP kinase pathway in HCT116 human colon cancer cells.

    Zeng, Huawei; Botnen, James H; Briske-Anderson, Mary

    2010-01-01

    The cell growth inhibition induced by bile acid deoxycholic acid (DCA) may cause compensatory hyperproliferation of colonic epithelial cells and consequently increase colon cancer risk. On the other hand, there is increasing evidence for the efficacy of certain forms of selenium (Se) as anticancer nutrients. Methylselenol has been hypothesized to be a critical Se metabolite for anticancer activity in vivo. In this study, we demonstrated that both DCA (75-300 micromol/l) and submicromolar methylselenol inhibited colon cancer cell proliferation by up to 64% and 63%, respectively. In addition, DCA and methylselenol each increased colon cancer cell apoptosis rate by up to twofold. Cell cycle analyses revealed that DCA induced an increase in only the G1 fraction with a concomitant drop in G2 and S-phase; in contrast, methylselenol led to an increase in the G1 and G2 fractions with a concomitant drop only in the S-phase. Although both DCA and methylselenol significantly promoted apoptosis and inhibited cell growth, examination of mitogen-activated protein kinase (MAPK) pathway activation showed that DCA, but not methylselenol, induced SAPK/JNK1/2, p38 MAPK, ERK1/2 activation. Thus, our data provide, for the first time, the molecular basis for opposite effects of methylselenol and DCA on colon tumorigenesis.

  4. Mannheim Curves in Nonflat 3-Dimensional Space Forms

    Wenjing Zhao

    2015-01-01

    Full Text Available We consider the Mannheim curves in nonflat 3-dimensional space forms (Riemannian or Lorentzian and we give the concept of Mannheim curves. In addition, we investigate the properties of nonnull Mannheim curves and their partner curves. We come to the conclusion that a necessary and sufficient condition is that a linear relationship with constant coefficients will exist between the curvature and the torsion of the given original curves. In the case of null curve, we reveal that there are no null Mannheim curves in the 3-dimensional de Sitter space.

  5. Ethyl Acetate Extract of Scindapsus cf. hederaceus Exerts the Inhibitory Bioactivity on Human Non-Small Cell Lung Cancer Cells through Modulating ER Stress

    Chon-Kit Chou

    2018-06-01

    Full Text Available Unfolded protein response (UPR is a cytoprotective mechanism that alleviates the protein-folding burden in eukaryotic organisms. Moderate activation of UPR is required for maintaining endoplasmic reticulum (ER homeostasis and profoundly contributes to tumorigenesis. Defects in UPR signaling are implicated in the attenuation of various malignant phenotypes including cell proliferation, migration, and invasion, as well as angiogenesis. This suggests UPR as a promising target in cancer therapy. The pharmacological effects of the plant Scindapsus cf. hederaceus on human cancer cell lines is not understood. In this study, we identified an ethyl acetate extract from Scindapsus cf. hederaceus (SH-EAE, which markedly altered the protein expression of UPR-related genes in human non-small cell lung cancer (NSCLC cells. Treatment with the SH-EAE led to the dose-dependent suppression of colony forming ability of both H1299 and H460 cells, but not markedly in normal bronchial epithelial BEAS-2B cells. SH-EAE treatment also attenuated the migration and invasion ability of H1299 and H460 cells. Moreover, SH-EAE strikingly suppressed the protein expression of two ER stress sensors, including inositol requiring enzyme-1α (IRE-1α and protein kinase R-like ER kinase (PERK, and antagonized the induction of C/EBP homologous protein (CHOP expression by thapsigargin, an ER stress inducer. SH-EAE induced the formation of massive vacuoles which are probably derived from ER. Importantly, SH-EAE impaired the formation of intersegmental vessels (ISV in zebrafish larvae, an index of angiogenesis, but had no apparent effect on the rate of larval development. Together, our findings demonstrate, for the first time, that the ability of SH-EAE specifically targets the two sensors of UPR, with significant anti-proliferation and anti-migration activities as a crude extract in human NSCLC cells. Our finding also indicates potential applications of SH-EAE in preventing UPR

  6. The bantam microRNA acts through Numb to exert cell growth control and feedback regulation of Notch in tumor-forming stem cells in the Drosophila brain.

    Wu, Yen-Chi; Lee, Kyu-Sun; Song, Yan; Gehrke, Stephan; Lu, Bingwei

    2017-05-01

    Notch (N) signaling is central to the self-renewal of neural stem cells (NSCs) and other tissue stem cells. Its deregulation compromises tissue homeostasis and contributes to tumorigenesis and other diseases. How N regulates stem cell behavior in health and disease is not well understood. Here we show that N regulates bantam (ban) microRNA to impact cell growth, a process key to NSC maintenance and particularly relied upon by tumor-forming cancer stem cells. Notch signaling directly regulates ban expression at the transcriptional level, and ban in turn feedback regulates N activity through negative regulation of the Notch inhibitor Numb. This feedback regulatory mechanism helps maintain the robustness of N signaling activity and NSC fate. Moreover, we show that a Numb-Myc axis mediates the effects of ban on nucleolar and cellular growth independently or downstream of N. Our results highlight intricate transcriptional as well as translational control mechanisms and feedback regulation in the N signaling network, with important implications for NSC biology and cancer biology.

  7. [In Vitro and In Vivo Biocompatibility of a Novel, 3-Dimensional Cellulose Matrix Structure].

    Dunda, S E; Ranker, M; Pallua, N; Machens, H-G; Ravichandran, A; Schantz, J-T

    2015-12-01

    Biological and physical characteristics of matrices are one essential factor in creating bioartificial tissue. In this study, a new 3-dimensional cellulose matrix (Xellulin(®)) was tested in terms of biocompatibility and applicability for tissue engineering in vitro and in vivo. The tested matrix Xellulin(®) is a natural hydrological gel-matrix containing bacterial cellulose and water. To evaluate the cell biocompatibilty, cell adherence and proliferation characteristics in vitro, the matrix was cultured with human fibroblasts. Further in vivo studies were carried out by transplanting preadipocytes of 4- to 6-week-old Wistar rats with 3 different conditions: a) Xellulin(®) including 500 000 preadipocytes subcutaneous, b) Xellulin(®) including 500 000 preadipocytes within an in vivo bioreactor chamber, c) Xellulin(®) without cells subcutaneous as control. After explantation on day 14 histomorphological and immunohistochemical evaluations were performed. In vitro study revealed an excellent biocompatibility with good cell adherence of the fibroblasts on the matrix and evidence of cell proliferation and creation of a 3-dimensional cell network. In vivo neocapillarisation could be shown in all groups with evidence of erythrocytes (H/E staining) and endothelial vascular cells (RECA-1-staining). A significantly higher vascular density was shown in vascularised bioreactor group (18.4 vessels/100 000 µm(2) (group b) vs. 8.1 (group a), pmatrix was noticed. The promising in vitro results concerning cell adherence and proliferation on the tested matrix could be confirmed in vivo with an evidence of 3-dimensional neocapillarisation. Cell survival was higher in the vascularised group, but without significance. Long-term tests (28-42 days) need to be carried out to evaluate long-term cell survival and the matrix stability. Furthermore, studies concerning the implementation of the matrix within anatomic structures as well as long-term biocompatibility are needed.

  8. Controlled teleportation of a 3-dimensional bipartite quantum state

    Cao Haijing; Chen Zhonghua; Song Heshan

    2008-01-01

    A controlled teleportation scheme of an unknown 3-dimensional (3D) two-particle quantum state is proposed, where a 3D Bell state and 3D GHZ state function as the quantum channel. This teleportation scheme can be directly generalized to teleport an unknown d-dimensional bipartite quantum state

  9. 3-Dimensional printing guide template assisted percutaneous vertebroplasty: Technical note.

    Li, Jian; Lin, JiSheng; Yang, Yong; Xu, JunChuan; Fei, Qi

    2018-06-01

    Percutaneous vertebroplasty (PVP) is currently considered as an effective treatment for pain caused by acute osteoporotic vertebral compression fracture. Recently, puncture-related complications are increasingly reported. It's important to find a precise technique to reduce the puncture-related complications. We report a case and discussed the novel surgical technique with step-by-step operating procedures, to introduce the precise PVP assisted by a 3-dimensional printing guide template. Based on the preoperative CT scan and infrared scan data, a well-designed individual guide template could be established in a 3-dimensional reconstruction software and printed out by a 3-dimensional printer. In real operation, by matching the guide template to patient's back skin, cement needles' insertion orientation and depth were easily established. Only 14 times C-arm fluoroscopy with HDF mode (total exposure dose was 4.5 mSv) were required during the procedure. The operation took only 17 min. Cement distribution in the vertebral body was very good without any puncture-related complications. Pain was significantly relieved after surgery. In conclusion, the novel precise 3-dimensional printing guide template system may allow (1) comprehensive visualization of the fractured vertebral body and the individual surgical planning, (2) the perfect fitting between skin and guide template to ensure the puncture stability and accuracy, and (3) increased puncture precision and decreased puncture-related complications, surgical time and radiation exposure. Copyright © 2018 Elsevier Ltd. All rights reserved.

  10. The ginsenoside PPD exerts anti-endometriosis effects by suppressing estrogen receptor-mediated inhibition of endometrial stromal cell autophagy and NK cell cytotoxicity.

    Zhang, Bing; Zhou, Wen-Jie; Gu, Chun-Jie; Wu, Ke; Yang, Hui-Li; Mei, Jie; Yu, Jia-Jun; Hou, Xiao-Fan; Sun, Jian-Song; Xu, Feng-Yuan; Li, Da-Jin; Jin, Li-Ping; Li, Ming-Qing

    2018-05-14

    Endometriosis (EMS) is an estrogen-dependent gynecological disease with a low autophagy level of ectopic endometrial stromal cells (eESCs). Impaired NK cell cytotoxic activity is involved in the clearance obstruction of the ectopic endometrial tissue in the abdominopelvic cavity. Protopanaxadiol (PPD) and protopanaxatriol (PPT) are two metabolites of ginsenosides, which have profound biological functions, such as anti-cancer activities. However, the role and mechanism of ginsenosides and metabolites in endometriosis are completely unknown. Here, we found that the compounds PPD, PPT, ginsenoside-Rg3 (G-Rg3), ginsenoside-Rh2 (G-Rh2), and esculentoside A (EsA) led to significant decreases in the viability of eESCs, particularly PPD (IC50 = 30.64 µM). In vitro and in vivo experiments showed that PPD promoted the expression of progesterone receptor (PR) and downregulated the expression of estrogen receptor α (ERα) in eESCs. Treatment with PPD obviously induced the autophagy of eESCs and reversed the inhibitory effect of estrogen on eESC autophagy. In addition, eESCs pretreated with PPD enhanced the cytotoxic activity of NK cells in response to eESCs. PPD decreased the numbers and suppressed the growth of ectopic lesions in a mouse EMS model. These results suggest that PPD plays a role in anti-EMS activation, possibly by restricting estrogen-mediated autophagy regulation and enhancing the cytotoxicity of NK cells. This result provides a scientific basis for potential therapeutic strategies to treat EMS by PPD or further structural modification.

  11. Adipose Tissue-Derived Mesenchymal Stem Cells Exert In Vitro Immunomodulatory and Beta Cell Protective Functions in Streptozotocin-Induced Diabetic Mice Model

    Hossein Rahavi

    2015-01-01

    Full Text Available Regenerative and immunomodulatory properties of mesenchymal stem cells (MSCs might be applied for type 1 diabetes mellitus (T1DM treatment. Thus, we proposed in vitro assessment of adipose tissue-derived MSCs (AT-MSCs immunomodulation on autoimmune response along with beta cell protection in streptozotocin- (STZ- induced diabetic C57BL/6 mice model. MSCs were extracted from abdominal adipose tissue of normal mice and cultured to proliferate. Diabetic mice were prepared by administration of multiple low-doses of streptozotocin. Pancreatic islets were isolated from normal mice and splenocytes prepared from normal and diabetic mice. Proliferation, cytokine production, and insulin secretion assays were performed in coculture experiments. AT-MSCs inhibited splenocytes proliferative response to specific (islet lysate and nonspecific (PHA triggers in a dose-dependent manner (P<0.05. Decreased production of proinflammatory cytokines, such as IFN-γ, IL-2, and IL-17, and increased secretion of regulatory cytokines such as TGF-β, IL-4, IL-10, and IL-13 by stimulated splenocytes were also shown in response to islet lysate or PHA stimulants (P<0.05. Finally, we demonstrated that AT-MSCs could effectively sustain viability as well as insulin secretion potential of pancreatic islets in the presence of reactive splenocytes (P<0.05. In conclusion, it seems that MSCs may provide a new horizon for T1DM cell therapy and islet transplantation in the future.

  12. The 3-dimensional core model DYN3D

    Grundmann, U.; Mittag, S.; Rohde, U.

    1999-01-01

    Analyzing the safety margins in transients and accidents of nuclear reactors 3-dimensional models of the core were used to avoid conservative assumptions needed for point kinetics or 1-dimensional models. Therefore, the 3D code DYN3D has been developed for the analysis of reactivity initiated accidents (RIA) in thermal nuclear reactors. The power distributions are calculated with the help of nodal expansion methods (NEM) for hexagonal and Cartesian geometry. The fuel rod model and the thermohydraulic part provide fuel temperatures, coolant temperatures and densities as well as boron concentrations for the calculation of feedback effects on the basis of cross section libraries generated by cell codes. Safety relevant parameters like maximum fuel and cladding temperatures, critical heat flux and degree of cladding oxidation are estimated. DYN3D can analyze RIA initiated by moved control rods and/or perturbations of the coolant flow. Stationary and transient boundary conditions for the coolant flow, the core inlet temperatures and boron concentrations at the core inlet have to be given. For analyzing more complex transients the code DYN3D is coupled with the plant model ATHLET of the GRS. The extensive validation work accomplished for DYN3D is presented in several examples. Some applications of the code are described. (orig.) [Deutsch] Die Verwendung 3-dimensionaler Kernmodelle zur Untersuchung der Sicherheitsreserven bei Uebergangsprozessen und Stoerfaellen in Kernreaktoren vermeidet konservative Annahmen, die bei der Benutzung des Punktmodells oder 1-dimensionaler Modelle erforderlich sind. Aus diesen Gruenden wurde das 3-dimensionale Rechenprogramm DYN3D fuer die Untersuchung von Reaktivitaetsstoerfaellen in thermischen Reaktoren entwickelt. Die Leistungsverteilung wird mit nodalen Methoden fuer hexagonale oder kartesische Geometrie berechnet. Das Brennstabmodell und der thermohydraulische Teil von DYN3D liefert die Brennstofftemperaturen, Kuehlmitteltemperaturen

  13. Interactive multimedia-based teaching material for 3-dimensional geometry

    Prabowo, A.; Anggoro, R. P.; Astuti, D.; Fahmi, S.

    2017-12-01

    This study aims to develop the interactive multimedia-based teaching material for 3-dimensional geometry in junior high school. The product was produced through the stages of define, design, develop, and disseminate. Two media experts and two teaching experts had validated it. They judged that the product developed was valid. It had been revised based on their advice. It has been disseminated to 15 mathematics teachers and tried to 30 students of junior high school. Teachers stated that this product gives a new form of teaching material in 3-dimensional geometry. According to the student, the product is interesting. It can motivate them to study mathematics, help them to master the material and increase their interest in mathematics.

  14. Wetting characteristics of 3-dimensional nanostructured fractal surfaces

    Davis, Ethan; Liu, Ying; Jiang, Lijia; Lu, Yongfeng; Ndao, Sidy

    2017-01-01

    This article reports the fabrication and wetting characteristics of 3-dimensional nanostructured fractal surfaces (3DNFS). Three distinct 3DNFS surfaces, namely cubic, Romanesco broccoli, and sphereflake were fabricated using two-photon direct laser writing. Contact angle measurements were performed on the multiscale fractal surfaces to characterize their wetting properties. Average contact angles ranged from 66.8° for the smooth control surface to 0° for one of the fractal surfaces. The change in wetting behavior was attributed to modification of the interfacial surface properties due to the inclusion of 3-dimensional hierarchical fractal nanostructures. However, this behavior does not exactly obey existing surface wetting models in the literature. Potential applications for these types of surfaces in physical and biological sciences are also discussed.

  15. Application of 3-dimensional CAD modeling system in nuclear plants

    Suwa, Minoru; Saito, Shunji; Nobuhiro, Minoru

    1990-01-01

    Until now, the preliminary work for mutual components in nuclear plant were readied by using plastic models. Recently with the development of computer graphic techniques, we can display the components on the graphics terminal, better than with use of plastic model and actual plants. The computer model can be handled, both telescopically and microscopically. A computer technique called 3-dimensional CAD modeling system was used as the preliminary work and design system. Through application of this system, database for nuclear plants was completed in arrangement step. The data can be used for piping design, stress analysis, shop production, testing and site construction, in all steps. In addition, the data can be used for various planning works, even after starting operation of plant. This paper describes the outline of the 3-dimensional CAD modeling system. (author)

  16. Cohomological rigidity of manifolds defined by 3-dimensional polytopes

    Buchstaber, V. M.; Erokhovets, N. Yu.; Masuda, M.; Panov, T. E.; Park, S.

    2017-04-01

    A family of closed manifolds is said to be cohomologically rigid if a cohomology ring isomorphism implies a diffeomorphism for any two manifolds in the family. Cohomological rigidity is established here for large families of 3-dimensional and 6-dimensional manifolds defined by 3-dimensional polytopes. The class \\mathscr{P} of 3-dimensional combinatorial simple polytopes P different from tetrahedra and without facets forming 3- and 4-belts is studied. This class includes mathematical fullerenes, that is, simple 3- polytopes with only 5-gonal and 6-gonal facets. By a theorem of Pogorelov, any polytope in \\mathscr{P} admits in Lobachevsky 3-space a right-angled realisation which is unique up to isometry. Our families of smooth manifolds are associated with polytopes in the class \\mathscr{P}. The first family consists of 3-dimensional small covers of polytopes in \\mathscr{P}, or equivalently, hyperbolic 3-manifolds of Löbell type. The second family consists of 6-dimensional quasitoric manifolds over polytopes in \\mathscr{P}. Our main result is that both families are cohomologically rigid, that is, two manifolds M and M' from either family are diffeomorphic if and only if their cohomology rings are isomorphic. It is also proved that if M and M' are diffeomorphic, then their corresponding polytopes P and P' are combinatorially equivalent. These results are intertwined with classical subjects in geometry and topology such as the combinatorics of 3-polytopes, the Four Colour Theorem, aspherical manifolds, a diffeomorphism classification of 6-manifolds, and invariance of Pontryagin classes. The proofs use techniques of toric topology. Bibliography: 69 titles.

  17. When exercise causes exertional rhabdomyolysis.

    Furman, Janet

    2015-04-01

    Exertional rhabdomyolysis is a clinical condition caused by intense, repetitive exercise or a sudden increase in exercise in an untrained person, although rhabdomyolysis can occur in trained athletes. In many cases, the presentation of early, uncomplicated rhabdomyolysis is subtle, but serious complications such as renal failure, compartment syndrome, and dysrhythmias may arise if severe exertional rhabdomyolysis is undiagnosed or untreated. Management is further complicated by the lack of concrete management guidelines for treating rhabdomyolysis and returning patients to activity.

  18. A study of 3-dimensionally periodic carbon nanostructures

    Yin, Ming; Bleiweiss, Michael; Amirzadeh, Jafar; Datta, Timir; Arammash, Fouzi

    2012-02-01

    Electronic structures with intricate periodic 3-dimensional arrangements at the submicron scale were investigated. These may be fabricated using artificial porous opal substrates as the templates in which the targeted conducting medium is introduced. In the past these materials were reported to show interesting electronic behaviors. [Michael Bleiweiss, et al ``Localization and Related Phenomena in Multiply Connected Nanostructured,'' BAPS, Z30.011, Nanostructured Materials Session, March 2001, Seattle]. Several materials were studied in particular disordered carbon which has been reported to show quantum transport including fractional hall steps. The results of these measurements, including the observation of localization phenomena, will be discussed. Comparisons will be made with literature data.

  19. On ruled surface in 3-dimensional almost contact metric manifold

    Karacan, Murat Kemal; Yuksel, Nural; Ikiz, Hasibe

    In this paper, we study ruled surface in 3-dimensional almost contact metric manifolds by using surface theory defined by Gök [Surfaces theory in contact geometry, PhD thesis (2010)]. We also studied the theory of curves using cross product defined by Camcı. In this study, we obtain the distribution parameters of the ruled surface and then some results and theorems are presented with special cases. Moreover, some relationships among asymptotic curve and striction line of the base curve of the ruled surface have been found.

  20. One New Method to Generate 3-Dimensional Virtual Mannequin

    Xiu-jin, Shi; Zhi-jun, Wang; Jia-jin, Le

    The personal virtual mannequin is very important in electronic made to measure (eMTM) system. There is one new easy method to generate personal virtual mannequin. First, the characteristic information of customer's body is got from two photos. Secondly, some human body part templates corresponding with the customer are selected from the templates library. Thirdly, these templates are modified and assembled according to certain rules to generate a personalized 3-dimensional human, and then the virtual mannequin is realized. Experimental result shows that the method is easy and feasible.

  1. Wetting characteristics of 3-dimensional nanostructured fractal surfaces

    Davis, Ethan, E-mail: ethan.davis4@huskers.unl.edu [Nano & Microsystems Research Laboratory, Department of Mechanical and Materials Engineering, University of Nebraska-Lincoln, W342 Nebraska Hall, Lincoln, NE 68588-0526 (United States); Liu, Ying; Jiang, Lijia; Lu, Yongfeng [Laser Assisted Nano Engineering Lab, Department of Electrical and Computer Engineering, University of Nebraska-Lincoln, 209N Scott Engineering Center, Lincoln, NE 68588-0511 (United States); Ndao, Sidy, E-mail: sndao2@unl.edu [Nano & Microsystems Research Laboratory, Department of Mechanical and Materials Engineering, University of Nebraska-Lincoln, W342 Nebraska Hall, Lincoln, NE 68588-0526 (United States)

    2017-01-15

    Highlights: • Hierarchically structured surfaces were fabricated on the micro/nano-scale. • These structures reduced the contact angle of the inherently hydrophilic material. • Similar surfaces have applications in two-phase heat transfer and microfluidics. - Abstract: This article reports the fabrication and wetting characteristics of 3-dimensional nanostructured fractal surfaces (3DNFS). Three distinct 3DNFS surfaces, namely cubic, Romanesco broccoli, and sphereflake were fabricated using two-photon direct laser writing. Contact angle measurements were performed on the multiscale fractal surfaces to characterize their wetting properties. Average contact angles ranged from 66.8° for the smooth control surface to 0° for one of the fractal surfaces. The change in wetting behavior was attributed to modification of the interfacial surface properties due to the inclusion of 3-dimensional hierarchical fractal nanostructures. However, this behavior does not exactly obey existing surface wetting models in the literature. Potential applications for these types of surfaces in physical and biological sciences are also discussed.

  2. Wetting characteristics of 3-dimensional nanostructured fractal surfaces

    Davis, Ethan; Liu, Ying; Jiang, Lijia; Lu, Yongfeng; Ndao, Sidy

    2017-01-01

    Highlights: • Hierarchically structured surfaces were fabricated on the micro/nano-scale. • These structures reduced the contact angle of the inherently hydrophilic material. • Similar surfaces have applications in two-phase heat transfer and microfluidics. - Abstract: This article reports the fabrication and wetting characteristics of 3-dimensional nanostructured fractal surfaces (3DNFS). Three distinct 3DNFS surfaces, namely cubic, Romanesco broccoli, and sphereflake were fabricated using two-photon direct laser writing. Contact angle measurements were performed on the multiscale fractal surfaces to characterize their wetting properties. Average contact angles ranged from 66.8° for the smooth control surface to 0° for one of the fractal surfaces. The change in wetting behavior was attributed to modification of the interfacial surface properties due to the inclusion of 3-dimensional hierarchical fractal nanostructures. However, this behavior does not exactly obey existing surface wetting models in the literature. Potential applications for these types of surfaces in physical and biological sciences are also discussed.

  3. The gastric acid secretagogue gastrin-releasing peptide and the inhibitor oxyntomodulin do not exert their effect directly on the parietal cell in the rat

    Poulsen, Steen Seier; Holst, J J

    1988-01-01

    in vitro by measuring [14C]-aminopyrine accumulation, a reliable index of H+ generation, in isolated rat parietal cells. However, neither gastrin-releasing peptide nor oxyntomodulin influenced basal acid secretion or histamine-stimulated gastric acid secretion. Electron-microscopic studies of unstimulated...... and histamine-stimulated parietal cells confirmed that the cells retained the normal morphology of intracellular organelles and that the cells responded to physiological stimulation by marked expansion of the intracellular canaliculi....

  4. Oleoylethanolamide exerts anti-inflammatory effects on LPS-induced THP-1 cells by enhancing PPARα signaling and inhibiting the NF-κB and ERK1/2/AP-1/STAT3 pathways.

    Yang, Lichao; Guo, Han; Li, Ying; Meng, Xianglan; Yan, Lu; Dan Zhang; Wu, Sangang; Zhou, Hao; Peng, Lu; Xie, Qiang; Jin, Xin

    2016-10-10

    The present study aimed to examine the anti-inflammatory actions of oleoylethanolamide (OEA) in lipopolysaccharide (LPS)-induced THP-1 cells. The cells were stimulated with LPS (1 μg/ml) in the presence or absence of OEA (10, 20 and 40 μM). The pro-inflammatory cytokines were evaluated by qRT-PCR and ELISA. The THP-1 cells were transiently transfected with PPARα small-interfering RNA, and TLR4 activity was determined with a blocking test using anti-TLR4 antibody. Additionally, a special inhibitor was used to analyse the intracellular signaling pathway. OEA exerted a potent anti-inflammatory effect by reducing the production of pro-inflammatory cytokines and TLR4 expression, and by enhancing PPARα expression. The modulatory effects of OEA on LPS-induced inflammation depended on PPARα and TLR4. Importantly, OEA inhibited LPS-induced NF-κB activation, IκBα degradation, expression of AP-1, and the phosphorylation of ERK1/2 and STAT3. In summary, our results demonstrated that OEA exerts anti-inflammatory effects by enhancing PPARα signaling, inhibiting the TLR4-mediated NF-κB signaling pathway, and interfering with the ERK1/2-dependent signaling cascade (TLR4/ERK1/2/AP-1/STAT3), which suggests that OEA may be a therapeutic agent for inflammatory diseases.

  5. Ganodermanontriol (GDNT) exerts its effect on growth and invasiveness of breast cancer cells through the down-regulation of CDC20 and uPA

    Jiang, Jiahua; Jedinak, Andrej; Sliva, Daniel

    2011-01-01

    Highlights: ► Ganodermanontriol (GDNT), a Ganoderma mushroom alcohol, inhibits growth of breast cancer cells. ► CDC20 is over-expressed in tumors but not in the tumor surrounding tissue in breast cancer patients. ► GDNT inhibits expression of CDC20 in breast cancer cells. ► GDNT inhibits cell adhesion, cell migration and cell invasion of breast cancer cells. ► GDNT inhibits secretion of uPA and down-regulates expression of uPAR in breast cancer cells. -- Abstract: Ganoderma lucidum is a medicinal mushroom that has been recognized by Traditional Chinese Medicine (TCM). Although some of the direct anticancer activities are attributed to the presence of triterpenes—ganoderic and lucidenic acids—the activity of other compounds remains elusive. Here we show that ganodermanontriol (GDNT), a Ganoderma alcohol, specifically suppressed proliferation (anchorage-dependent growth) and colony formation (anchorage-independent growth) of highly invasive human breast cancer cells MDA-MB-231. GDNT suppressed expression of the cell cycle regulatory protein CDC20, which is over-expressed in precancerous and breast cancer cells compared to normal mammary epithelial cells. Moreover, we found that CDC20 is over-expressed in tumors when compared to the tissue surrounding the tumor in specimens from breast cancer patients. GDNT also inhibited invasive behavior (cell adhesion, cell migration, and cell invasion) through the suppression of secretion of urokinase-plasminogen activator (uPA) and inhibited expression of uPA receptor. In conclusion, mushroom GDNT is a natural agent that has potential as a therapy for invasive breast cancers.

  6. Ganodermanontriol (GDNT) exerts its effect on growth and invasiveness of breast cancer cells through the down-regulation of CDC20 and uPA

    Jiang, Jiahua; Jedinak, Andrej [Cancer Research Laboratory, Methodist Research Institute, Indiana University Health, Indianapolis, IN (United States); Sliva, Daniel, E-mail: dsliva@iuhealth.org [Cancer Research Laboratory, Methodist Research Institute, Indiana University Health, Indianapolis, IN (United States); Department of Medicine, School of Medicine, Indiana University, Indianapolis, IN (United States); Indiana University Simon Cancer Center, School of Medicine, Indiana University, Indianapolis, IN (United States)

    2011-11-18

    Highlights: Black-Right-Pointing-Pointer Ganodermanontriol (GDNT), a Ganoderma mushroom alcohol, inhibits growth of breast cancer cells. Black-Right-Pointing-Pointer CDC20 is over-expressed in tumors but not in the tumor surrounding tissue in breast cancer patients. Black-Right-Pointing-Pointer GDNT inhibits expression of CDC20 in breast cancer cells. Black-Right-Pointing-Pointer GDNT inhibits cell adhesion, cell migration and cell invasion of breast cancer cells. Black-Right-Pointing-Pointer GDNT inhibits secretion of uPA and down-regulates expression of uPAR in breast cancer cells. -- Abstract: Ganoderma lucidum is a medicinal mushroom that has been recognized by Traditional Chinese Medicine (TCM). Although some of the direct anticancer activities are attributed to the presence of triterpenes-ganoderic and lucidenic acids-the activity of other compounds remains elusive. Here we show that ganodermanontriol (GDNT), a Ganoderma alcohol, specifically suppressed proliferation (anchorage-dependent growth) and colony formation (anchorage-independent growth) of highly invasive human breast cancer cells MDA-MB-231. GDNT suppressed expression of the cell cycle regulatory protein CDC20, which is over-expressed in precancerous and breast cancer cells compared to normal mammary epithelial cells. Moreover, we found that CDC20 is over-expressed in tumors when compared to the tissue surrounding the tumor in specimens from breast cancer patients. GDNT also inhibited invasive behavior (cell adhesion, cell migration, and cell invasion) through the suppression of secretion of urokinase-plasminogen activator (uPA) and inhibited expression of uPA receptor. In conclusion, mushroom GDNT is a natural agent that has potential as a therapy for invasive breast cancers.

  7. Myeloid derived suppressor cells (MDSCs are increased and exert immunosuppressive activity together with polymorphonuclear leukocytes (PMNs in chronic myeloid leukemia patients.

    Cesarina Giallongo

    Full Text Available Tumor immune tolerance can derive from the recruitment of suppressor cell population, including myeloid derived suppressor cells (MDSCs, able to inhibit T cells activity. We identified a significantly expanded MDSCs population in chronic myeloid leukemia (CML patients at diagnosis that decreased to normal levels after imatinib therapy. In addition, expression of arginase 1 (Arg1 that depletes microenvironment of arginine, an essential aminoacid for T cell function, resulted in an increase in patients at diagnosis. Purified CML CD11b+CD33+CD14-HLADR- cells markedly suppressed normal donor T cell proliferation in vitro. Comparing CML Gr-MDSCs to autologous polymorphonuclear leukocytes (PMNs we observed a higher Arg1 expression and activity in PMNs, together with an inhibitory effect on T cells in vitro. Our data indicate that CML cells create an immuno-tolerant environment associated to MDSCs expansion with immunosuppressive capacity mediated by Arg1. In addition, we demonstrated for the first time also an immunosuppressive activity of CML PMNs, suggesting a strong potential immune escape mechanism created by CML cells, which control the anti-tumor reactive T cells. MDSCs should be monitored in imatinib discontinuation trials to understand their importance in relapsing patients.

  8. Portulaca oleracea Seed Oil Exerts Cytotoxic Effects on Human Liver Cancer (HepG2) and Human Lung Cancer (A-549) Cell Lines.

    Al-Sheddi, Ebtesam Saad; Farshori, Nida Nayyar; Al-Oqail, Mai Mohammad; Musarrat, Javed; Al-Khedhairy, Abdulaziz Ali; Siddiqui, Maqsood Ahmed

    2015-01-01

    Portulaca oleracea (Family: Portulacaceae), is well known for its anti-inflammatory, antioxidative, anti- bacterial, and anti-tumor activities. However, cytotoxic effects of seed oil of Portulaca oleracea against human liver cancer (HepG2) and human lung cancer (A-549) cell lines have not been studied previously. Therefore, the present study was designed to investigate the cytotoxic effects of Portulaca oleracea seed oil on HepG2 and A-549 cell lines. Both cell lines were exposed to various concentrations of Portulaca oleracea seed oil for 24h. After the exposure, percentage cell viability was studied by (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) (MTT), neutral red uptake (NRU) assays, and cellular morphology by phase contrast inverted microscopy. The results showed a concentration-dependent significant reduction in the percentage cell viability and an alteration in the cellular morphology of HepG2 and A-549 cells. The percentage cell viability was recorded as 73%, 63%, and 54% by MTT assay and 76%, 61%, and 50% by NRU assay at 250, 500, and 1000 μg/ml, respectively in HepG2 cells. Percentage cell viability was recorded as 82%, 72%, and 64% by MTT assay and 83%, 68%, and 56% by NRU assay at 250, 500, and 1000 μg/ml, respectively in A-549 cells. The 100 μg/ml and lower concentrations were found to be non cytotoxic to A-549 cells, whereas decrease of 14% and 12% were recorded by MTT and NRU assay, respectively in HepG2 cells. Both HepG2 and A-549 cell lines exposed to 250, 500, and 1000 μg/ ml of Portulaca oleracea seed oil lost their normal morphology, cell adhesion capacity, become rounded, and appeared smaller in size. The data from this study showed that exposure to seed oil of Portulaca oleracea resulted in significant cytotoxicity and inhibition of growth of the human liver cancer (HepG2) and human lung cancer (A-549) cell lines.

  9. Pathophysiology of Degenerative Mitral Regurgitation: New 3-Dimensional Imaging Insights.

    Antoine, Clemence; Mantovani, Francesca; Benfari, Giovanni; Mankad, Sunil V; Maalouf, Joseph F; Michelena, Hector I; Enriquez-Sarano, Maurice

    2018-01-01

    Despite its high prevalence, little is known about mechanisms of mitral regurgitation in degenerative mitral valve disease apart from the leaflet prolapse itself. Mitral valve is a complex structure, including mitral annulus, mitral leaflets, papillary muscles, chords, and left ventricular walls. All these structures are involved in physiological and pathological functioning of this valvuloventricular complex but up to now were difficult to analyze because of inherent limitations of 2-dimensional imaging. The advent of 3-dimensional echocardiography, computed tomography, and cardiac magnetic resonance imaging overcoming these limitations provides new insights into mechanistic analysis of degenerative mitral regurgitation. This review will detail the contribution of quantitative and qualitative dynamic analysis of mitral annulus and mitral leaflets by new imaging methods in the understanding of degenerative mitral regurgitation pathophysiology. © 2018 American Heart Association, Inc.

  10. 3-Dimensional Agent Representations Increase Generosity in a Naturalistic Setting

    Krátký, Jan; McGraw, John J.; Xygalatas, Dimitris

    do not always act as deliberative, rational actors. Various studies have investigated the effects of both material cues and complex environmental settings on behavioral choices. One particularly common and salient aspect of the environment involves cues related to intentional agents, whether...... they be our conspecifics, non-human species or supernatural beings. A number of studies have found that exposing participants to cues of agency increase prosocial or cooperative behavior. In two separate studies, we investigated the role dimensionality plays in priming inferences of agency. In contrast...... to previous studies utilizing 2-dimensional images, 3-dimensional representations share morphological elements with real life agents which may enhance the salience of the cues. Higher activation of agency detection, in turn, ought to trigger stronger reputational concerns and thus further amplify prosocial...

  11. Scientific visualization of 3-dimensional optimized stellarator configurations

    Spong, D.A.

    1998-01-01

    The design techniques and physics analysis of modern stellarator configurations for magnetic fusion research rely heavily on high performance computing and simulation. Stellarators, which are fundamentally 3-dimensional in nature, offer significantly more design flexibility than more symmetric devices such as the tokamak. By varying the outer boundary shape of the plasma, a variety of physics features, such as transport, stability, and heating efficiency can be optimized. Scientific visualization techniques are an important adjunct to this effort as they provide a necessary ergonomic link between the numerical results and the intuition of the human researcher. The authors have developed a variety of visualization techniques for stellarators which both facilitate the design optimization process and allow the physics simulations to be more readily understood

  12. Review of 3-Dimensional Printing on Cranial Neurosurgery Simulation Training.

    Vakharia, Vejay N; Vakharia, Nilesh N; Hill, Ciaran S

    2016-04-01

    Shorter working times, reduced operative exposure to complex procedures, and increased subspecialization have resulted in training constraints within most surgical fields. Simulation has been suggested as a possible means of acquiring new surgical skills without exposing patients to the surgeon's operative "learning curve." Here we review the potential impact of 3-dimensional printing on simulation and training within cranial neurosurgery and its implications for the future. In accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines, a comprehensive search of PubMed, OVID MEDLINE, Embase, and the Cochrane Database of Systematic Reviews was performed. In total, 31 studies relating to the use of 3-dimensional (3D) printing within neurosurgery, of which 16 were specifically related to simulation and training, were identified. The main impact of 3D printing on neurosurgical simulation training was within vascular surgery, where patient-specific replication of vascular anatomy and pathologies can aid surgeons in operative planning and clip placement for reconstruction of vascular anatomy. Models containing replicas of brain tumors have also been reconstructed and used for training purposes, with some providing realistic representations of skin, subcutaneous tissue, bone, dura, normal brain, and tumor tissue. 3D printing provides a unique means of directly replicating patient-specific pathologies. It can identify anatomic variation and provide a medium in which training models can be generated rapidly, allowing the trainee and experienced neurosurgeon to practice parts of operations preoperatively. Future studies are required to validate this technology in comparison with current simulators and show improved patient outcomes. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Long Term Exposure to Polyphenols of Artichoke (Cynara scolymus L.) Exerts Induction of Senescence Driven Growth Arrest in the MDA-MB231 Human Breast Cancer Cell Line.

    Mileo, Anna Maria; Di Venere, Donato; Abbruzzese, Claudia; Miccadei, Stefania

    2015-01-01

    Polyphenolic extracts from the edible part of artichoke (Cynara scolymus L.) have been shown to be potential chemopreventive and anticancer dietary compounds. High doses of polyphenolic extracts (AEs) induce apoptosis and decrease the invasive potential of the human breast cancer cell line, MDA-MB231. However, the molecular mechanism underlying AEs antiproliferative effects is not completely understood. We demonstrate that chronic and low doses of AEs treatment at sublethal concentrations suppress human breast cancer cell growth via a caspases-independent mechanism. Furthermore, AEs exposure induces a significant increase of senescence-associated β-galactosidase (SA-β-gal) staining and upregulation of tumour suppressor genes, p16(INK4a) and p21(Cip1/Waf1) in MDA-MB231 cells. AEs treatment leads to epigenetic alterations in cancer cells, modulating DNA hypomethylation and lysine acetylation levels in total proteins. Cell growth arrest correlates with increased reactive oxygen species (ROS) production in AEs treated breast cancer cells. Inhibition of ROS generation by N-acetylcysteine (NAC) attenuates the antiproliferative effect. These findings demonstrate that chronic AEs treatment inhibits breast cancer cell growth via the induction of premature senescence through epigenetic and ROS-mediated mechanisms. Our results suggest that artichoke polyphenols could be a promising dietary tool either in cancer chemoprevention or/and in cancer treatment as a nonconventional, adjuvant therapy.

  14. Ovatodiolide of Anisomeles indica Exerts the Anticancer Potential on Pancreatic Cancer Cell Lines through STAT3 and NF-κB Regulation

    Ya-Ju Hsieh

    2016-01-01

    Full Text Available Pancreatic cancer is the eighth leading cause of cancer death worldwide. Patients with pancreatic cancer are normally diagnosed at an advanced stage and present poor survival rate. Ovatodiolide (OV, a bioactive macrocyclic diterpenoid isolated from Anisomeles indica, showed cytotoxicity effects in pancreatic cancer cells by inhibiting cell proliferation and inducing apoptosis. Moreover, not only were cell adhesion and invasion markedly suppressed in a dose-dependent manner, but the mRNA expression of matrix metalloproteinase-9 (MMP-9 and focal adhesion kinase (FAK was also significantly decreased. Western blot analysis indicated that OV potently suppressed the phosphorylation of STAT-3 and its upstream kinase including ERK1/2, P38, and AKT Ser473. Meanwhile, OV inactivated the nuclear factor kappa B (NF-κB by inhibiting IκB kinase (IKK α/β activation and the subsequent suppression of inhibitor of kappa B (IκB phosphorylation. These results demonstrated that OV could potentially inhibit Mia-PaCa2 cancer cells proliferation and induce apoptosis through modulation of NF-κB and STAT3 pathway. Moreover, OV suppressed cell invasiveness and interfered with cell-matrix adhesion in Mia-PaCa2 cancer cells by reducing MMP-9 and FAK transcription through suppressing NF-κB and STAT3 pathway. Taken together, our findings reveal a new therapeutic and antimetastatic potential of ovatodiolide for pancreatic cancer remedy.

  15. Stat5 Exerts Distinct, Vital Functions in the Cytoplasm and Nucleus of Bcr-Abl+ K562 and Jak2(V617F)+ HEL Leukemia Cells

    Weber, Axel; Borghouts, Corina; Brendel, Christian; Moriggl, Richard; Delis, Natalia; Brill, Boris; Vafaizadeh, Vida; Groner, Bernd

    2015-01-01

    Signal transducers and activators of transcription (Stats) play central roles in the conversion of extracellular signals, e.g., cytokines, hormones and growth factors, into tissue and cell type specific gene expression patterns. In normal cells, their signaling potential is strictly limited in extent and duration. The persistent activation of Stat3 or Stat5 is found in many human tumor cells and contributes to their growth and survival. Stat5 activation plays a pivotal role in nearly all hematological malignancies and occurs downstream of oncogenic kinases, e.g., Bcr-Abl in chronic myeloid leukemias (CML) and Jak2(V617F) in other myeloproliferative diseases (MPD). We defined the mechanisms through which Stat5 affects growth and survival of K562 cells, representative of Bcr-Abl positive CML, and HEL cells, representative for Jak2(V617F) positive acute erythroid leukemia. In our experiments we suppressed the protein expression levels of Stat5a and Stat5b through shRNA mediated downregulation and demonstrated the dependence of cell survival on the presence of Stat5. Alternatively, we interfered with the functional capacities of the Stat5 protein through the interaction with a Stat5 specific peptide ligand. This ligand is a Stat5 specific peptide aptamer construct which comprises a 12mer peptide integrated into a modified thioredoxin scaffold, S5-DBD-PA. The peptide sequence specifically recognizes the DNA binding domain (DBD) of Stat5. Complex formation of S5-DBD-PA with Stat5 causes a strong reduction of P-Stat5 in the nuclear fraction of Bcr-Abl-transformed K562 cells and a suppression of Stat5 target genes. Distinct Stat5 mediated survival mechanisms were detected in K562 and Jak2(V617F)-transformed HEL cells. Stat5 is activated in the nuclear and cytosolic compartments of K562 cells and the S5-DBD-PA inhibitor most likely affects the viability of Bcr-Abl + K562 cells through the inhibition of canonical Stat5 induced target gene transcription. In HEL cells, Stat5

  16. Acetylation of cell wall is required for structural integrity of the leaf surface and exerts a global impact on plant stress responses

    Nafisi, Majse; Stranne, Maria; Fimognari, Lorenzo

    2015-01-01

    The epidermis on leaves protects plants from pathogen invasion and provides a waterproof barrier. It consists of a layer of cells that is surrounded by thick cell walls, which are partially impregnated by highly hydrophobic cuticular components. We show that the Arabidopsis T-DNA insertion mutants...... to abiotic stress, particularly detoxification of reactive oxygen species and defense against microbial pathogens (e.g., lipid transfer proteins, peroxidases). In accordance, peroxidase activities were found to be elevated in rwa2 as compared to the wild type. These results indicate that cell wall...

  17. Reovirus exerts potent oncolytic effects in head and neck cancer cell lines that are independent of signalling in the EGFR pathway

    Twigger, Katie; Coffey, Matt; Thompson, Brad; Jebar, Adel; Errington, Fiona; Melcher, Alan A; Vile, Richard G; Pandha, Hardev S; Harrington, Kevin J; Roulstone, Victoria; Kyula, Joan; Karapanagiotou, Eleni M; Syrigos, Konstantinos N; Morgan, Richard; White, Christine; Bhide, Shreerang; Nuovo, Gerard

    2012-01-01

    Reovirus exploits aberrant signalling downstream of Ras to mediate tumor-specific oncolysis. Since ~90% squamous cell carcinomas of the head and neck (SCCHN) over-express EGFR and SCCHN cell lines are sensitive to oncolytic reovirus, we conducted a detailed analysis of the effects of reovirus in 15 head and neck cancer cell lines. Both pre- and post-entry events were studied in an attempt to define biomarkers predictive of sensitivity/resistance to reovirus. In particular, we analysed the role of EGFR/Ras signalling in determining virus-mediated cytotoxicity in SCCHN. To test whether EGFR pathway activity was predictive of increased sensitivity to reovirus, correlative analyses between reoviral IC50 by MTT assay and EGFR levels by western blot and FACS were conducted. Inhibition or stimulation of EGFR signalling were analysed for their effect on reoviral oncolysis by MTT assay, and viral growth by TCID50 assay. We next analysed the effects of inhibiting signalling downstream of Ras, by specific inhibitors of p38MAPK, PI3-K or MEK, on reoviral killing examined by MTT assay. The role of PKR in reoviral killing was also determined by blockade of PKR using 2-aminopurine and assaying for cell survival by MTT assay. The apoptotic response of SCCHN to reovirus was examined by western blot analysis of caspase 3 cleavage. Correlative analyses between reoviral sensitivity and EGFR levels revealed no association. Intermediate sub-viral and core particles showed the same infectivity/cytotoxicity as intact reovirus. Therefore, sensitivity was not determined by cell entry. In 4 cell lines, oncolysis and viral growth were both unaffected by inhibition or stimulation of EGFR signalling. Inhibition of signalling downstream of Ras did not abrogate reoviral oncolysis and, in addition, modulation of PKR using 2-aminopurine did not alter reovirus sensitivity in resistant cell lines. Caspase 3 cleavage was not detected in infected cells and oncolysis was observed in pan

  18. Mangiferin exerts antitumor activity in breast cancer cells by regulating matrix metalloproteinases, epithelial to mesenchymal transition, and β-catenin signaling pathway

    Li, Hongzhong; Huang, Jing; Yang, Bing; Xiang, Tingxiu; Yin, Xuedong; Peng, Weiyan; Cheng, Wei [Molecular Oncology and Epigenetics Laboratory, The First Affiliated Hospital of Chongqing Medical University, Chongqing (China); Wan, Jingyuan; Luo, Fuling [Department of Pharmacology, Chongqing Medical University, Chongqing (China); Li, Hongyuan [Molecular Oncology and Epigenetics Laboratory, The First Affiliated Hospital of Chongqing Medical University, Chongqing (China); Ren, Guosheng, E-mail: rgs726@163.com [Molecular Oncology and Epigenetics Laboratory, The First Affiliated Hospital of Chongqing Medical University, Chongqing (China)

    2013-10-01

    Although mangiferin which is a naturally occurring glucosylxanthone has exhibited promising anticancer activities, the detailed molecular mechanism of mangiferin on cancers still remains enigmatic. In this study, the anticancer activity of mangiferin was evaluated in breast cancer cell line-based in vitro and in vivo models. We showed that mangiferin treatment resulted in decreased cell viability and suppression of metastatic potential in breast cancer cells. Further mechanistic investigation revealed that mangiferin induced decreased matrix metalloproteinase (MMP)-7 and -9, and reversal of epithelial–mesenchymal transition (EMT). Moreover, it was demonstrated that mangiferin significantly inhibited the activation of β-catenin pathway. Subsequent experiments showed that inhibiting β-catenin pathway might play a central role in mangiferin-induced anticancer activity through modulation of MMP-7 and -9, and EMT. Consistent with these findings in vitro, the antitumor potential was also verified in mangiferin-treated MDA-MB-231 xenograft mice where significantly decreased tumor volume, weight and proliferation, and increased apoptosis were obtained, with lower expression of MMP-7 and -9, vimentin and active β-catenin, and higher expression of E-cadherin. Taken together, our study suggests that mangiferin might be used as an effective chemopreventive agent against breast cancer. - Highlights: • Mangiferin inhibits growth and metastatic potential in breast cancer cells. • Mangiferin down-regulates MMP-7 and -9 in breast cancer cells. • Mangiferin induces the reversal of EMT in metastatic breast cancer cells. • Mangiferin inhibits the activation of β-catenin pathway in breast cancer cells. • Inhibiting β-catenin is responsible for the antitumor activity of mangiferin.

  19. Icariin and its derivative, ICT, exert anti-inflammatory, anti-tumor effects, and modulate myeloid derived suppressive cells (MDSCs) functions.

    Zhou, Junmin; Wu, Jinfeng; Chen, Xianghong; Fortenbery, Nicole; Eksioglu, Erika; Kodumudi, Krithika N; Pk, Epling-Burnette; Dong, Jingcheng; Djeu, Julie Y; Wei, Sheng

    2011-07-01

    3, 5,7-trihydroxy-4'-methoxy-8-(3-hydroxy-3-methylbutyl)-flavone (ICT) is a novel derivative of Icariin (ICA), the major active ingredient of Herba Epimedii, a herb used in traditional Chinese and alternative medicine. We previously demonstrated its anti-inflammatory effect in murine innate immune cells and activated human PBMCs. We report herein that ICA or ICT treatment reduces the expression of MRP8/MRP14 and toll-like receptor 4 (TLR4) on human PBMCs. Administration of ICA or ICT inhibited tumor growth in 4T1-Neu tumor-bearing mice and considerably decreased MDSC numbers in the spleen of these mice. Further, we saw a restoration of IFN-γ production by CD8+ T cells in tumor bearing mice when treated with ICA or ICT. ICA and ICT significantly decreased the amounts of nitric oxide and reactive oxygen species in MDSC in vivo. When MDSC were treated in vitro with ICT, we saw a significant reduction in the percent of these cells with concomitant differentiation into dendritic cells and macrophages. Concomitant with this cell type conversion was a down-regulation of IL-10, IL-6 and TNF-α production. Decreased expression of S100A8/9 and inhibition of activation of STAT3 and AKT may in part be responsible for the observed results. In conclusion, our results showed that ICA, and more robustly, ICT, directly modulate MDSC signaling and therefore altered the phenotype and function of these cells, in vitro and in vivo. Copyright © 2010 Elsevier B.V. All rights reserved.

  20. Novel BET protein proteolysis-targeting chimera exerts superior lethal activity than bromodomain inhibitor (BETi) against post-myeloproliferative neoplasm secondary (s) AML cells.

    Saenz, D T; Fiskus, W; Qian, Y; Manshouri, T; Rajapakshe, K; Raina, K; Coleman, K G; Crew, A P; Shen, A; Mill, C P; Sun, B; Qiu, P; Kadia, T M; Pemmaraju, N; DiNardo, C; Kim, M-S; Nowak, A J; Coarfa, C; Crews, C M; Verstovsek, S; Bhalla, K N

    2017-09-01

    The PROTAC (proteolysis-targeting chimera) ARV-825 recruits bromodomain and extraterminal (BET) proteins to the E3 ubiquitin ligase cereblon, leading to degradation of BET proteins, including BRD4. Although the BET-protein inhibitor (BETi) OTX015 caused accumulation of BRD4, treatment with equimolar concentrations of ARV-825 caused sustained and profound depletion (>90%) of BRD4 and induced significantly more apoptosis in cultured and patient-derived (PD) CD34+ post-MPN sAML cells, while relatively sparing the CD34+ normal hematopoietic progenitor cells. RNA-Seq, Reverse Phase Protein Array and mass cytometry 'CyTOF' analyses demonstrated that ARV-825 caused greater perturbations in messenger RNA (mRNA) and protein expressions than OTX015 in sAML cells. Specifically, compared with OTX015, ARV-825 treatment caused more robust and sustained depletion of c-Myc, CDK4/6, JAK2, p-STAT3/5, PIM1 and Bcl-xL, while increasing the levels of p21 and p27. Compared with OTX015, PROTAC ARV-771 treatment caused greater reduction in leukemia burden and further improved survival of NSG mice engrafted with luciferase-expressing HEL92.1.7 cells. Co-treatment with ARV-825 and JAK inhibitor ruxolitinib was synergistically lethal against established and PD CD34+ sAML cells. Notably, ARV-825 induced high levels of apoptosis in the in vitro generated ruxolitinib-persister or ruxolitinib-resistant sAML cells. These findings strongly support the in vivo testing of the BRD4-PROTAC based combinations against post-MPN sAML.

  1. PWR core safety analysis with 3-dimensional methods

    Gensler, A.; Kühnel, K.; Kuch, S.

    2015-01-01

    Highlights: • An overview of AREVA’s safety analysis codes their coupling is provided. • The validation base and licensing applications of these codes are summarized. • Coupled codes and methods provide improved margins and non-conservative results. • Examples for REA and inadvertent opening of the pressurizer safety valve are given. - Abstract: The main focus of safety analysis is to demonstrate the required safety level of the reactor core. Because of the demanding requirements, the quality of the safety analysis strongly affects the confidence in the operational safety of a reactor. To ensure the highest quality, it is essential that the methodology consists of appropriate analysis tools, an extensive validation base, and last but not least highly educated engineers applying the methodology. The sophisticated 3-dimensional core models applied by AREVA ensure that all physical effects relevant for safety are treated and the results are reliable and conservative. Presently AREVA employs SCIENCE, CASMO/NEMO and CASCADE-3D for pressurized water reactors. These codes are currently being consolidated into the next generation 3D code system ARCADIA®. AREVA continuously extends the validation base, including measurement campaigns in test facilities and comparisons of the predictions of steady state and transient measured data gathered from plants during many years of operation. Thus, the core models provide reliable and comprehensive results for a wide range of applications. For the application of these powerful tools, AREVA is taking benefit of its interdisciplinary know-how and international teamwork. Experienced engineers of different technical backgrounds are working together to ensure an appropriate interpretation of the calculation results, uncertainty analysis, along with continuously maintaining and enhancing the quality of the analysis methodologies. In this paper, an overview of AREVA’s broad application experience as well as the broad validation

  2. A novel compound NSC745885 exerts an anti-tumor effect on tongue cancer SAS cells in vitro and in vivo.

    Yuan-Wu Chen

    Full Text Available Oral squamous cell carcinoma (OSCC is a prevalent cancer, especially in developing countries. Anthracyclines and their anthraquinone derivatives, such as doxorubicin, exhibit a cell growth inhibitory effect and have been used as anti-cancer drugs for many years. However, the cardiotoxicity of anthracycline antibiotics is a major concern in their clinical application. NSC745885 is a novel compound synthesized from 1,2-diaminoanthraquinone, which subsequently reacts with thionyl chloride and triethylamine. The present study aimed to investigate the anti-oral cancer potential and the safety of NSC745885.We investigated the anti-cancer potential of NSC745885 in oral squamous carcinoma cell lines and in an in vivo oral cancer xenograft mouse model. The expression of apoptotic related genes were evaluated by real-time RT-PCR and western bloting, and the in vivo assessment of apoptotic marker were measured by immunohistochemical staining. The anti-tumor efficiency and safety between doxorubicin and NSC745885 were also compared.Our results demonstrated that NSC745885 exhibits anti-oral cancer activity through the induction of apoptosis in cancer cells and in tumor-bearing mice, and this treatment did not induce marked toxicity in experimental mice. This compound also exhibits a comparable anti-tumor efficiency and a higher safety in experimental mice when compared to doxorubicin.The data of this study provide evidence for NSC745885 as a potential novel therapeutic drug for the treatment of human OSCC.

  3. Copper(ii) oxide nanoparticles penetrate into HepG2 cells, exert cytotoxicity via oxidative stress and induce pro-inflammatory response

    Piret, Jean-Pascal; Jacques, Diane; Audinot, Jean-Nicolas; Mejia, Jorge; Boilan, Emmanuelle; Noël, Florence; Fransolet, Maude; Demazy, Catherine; Lucas, Stéphane; Saout, Christelle; Toussaint, Olivier

    2012-10-01

    The potential toxic effects of two types of copper(ii) oxide (CuO) nanoparticles (NPs) with different specific surface areas, different shapes (rod or spheric), different sizes as raw materials and similar hydrodynamic diameter in suspension were studied on human hepatocarcinoma HepG2 cells. Both CuO NPs were shown to be able to enter into HepG2 cells and induce cellular toxicity by generating reactive oxygen species. CuO NPs increased the abundance of several transcripts coding for pro-inflammatory interleukins and chemokines. Transcriptomic data, siRNA knockdown and DNA binding activities suggested that Nrf2, NF-κB and AP-1 were implicated in the response of HepG2 cells to CuO NPs. CuO NP incubation also induced activation of MAPK pathways, ERKs and JNK/SAPK, playing a major role in the activation of AP-1. In addition, cytotoxicity, inflammatory and antioxidative responses and activation of intracellular transduction pathways induced by rod-shaped CuO NPs were more important than spherical CuO NPs. Measurement of Cu2+ released in cell culture medium suggested that Cu2+ cations released from CuO NPs were involved only to a small extent in the toxicity induced by these NPs on HepG2 cells.The potential toxic effects of two types of copper(ii) oxide (CuO) nanoparticles (NPs) with different specific surface areas, different shapes (rod or spheric), different sizes as raw materials and similar hydrodynamic diameter in suspension were studied on human hepatocarcinoma HepG2 cells. Both CuO NPs were shown to be able to enter into HepG2 cells and induce cellular toxicity by generating reactive oxygen species. CuO NPs increased the abundance of several transcripts coding for pro-inflammatory interleukins and chemokines. Transcriptomic data, siRNA knockdown and DNA binding activities suggested that Nrf2, NF-κB and AP-1 were implicated in the response of HepG2 cells to CuO NPs. CuO NP incubation also induced activation of MAPK pathways, ERKs and JNK/SAPK, playing a major

  4. Δ⁹-tetrahydrocannabinol (Δ⁹-THC) exerts a direct neuroprotective effect in a human cell culture model of Parkinson's disease.

    Carroll, C B; Zeissler, M-L; Hanemann, C O; Zajicek, J P

    2012-10-01

    Δ⁹-tetrahydrocannabinol (Δ⁹-THC) is neuroprotective in models of Parkinson's disease (PD). Although CB1 receptors are increased within the basal ganglia of PD patients and animal models, current evidence suggests a role for CB1 receptor-independent mechanisms. Here, we utilized a human neuronal cell culture PD model to further investigate the protective properties of Δ⁹-THC. Differentiated SH-SY5Y neuroblastoma cells were exposed to PD-relevant toxins: 1-methyl-4-phenylpyridinium (MPP+), lactacystin and paraquat. Changes in CB1 receptor level were determined by quantitative polymerase chain reaction and Western blotting. Cannabinoids and modulatory compounds were co-administered with toxins for 48 h and the effects on cell death, viability, apoptosis and oxidative stress assessed. We found CB1 receptor up-regulation in response to MPP+, lactacystin and paraquat and a protective effect of Δ⁹-THC against all three toxins. This neuroprotective effect was not reproduced by the CB1 receptor agonist WIN55,212-2 or blocked by the CB1 antagonist AM251. Furthermore, the antioxidants α-tocopherol and butylhydroxytoluene as well as the antioxidant cannabinoids, nabilone and cannabidiol were unable to elicit the same neuroprotection as Δ⁹-THC. However, the peroxisome proliferator-activated receptor-gamma (PPARγ) antagonist T0070907 dose-dependently blocked the neuroprotective, antioxidant and anti-apoptotic effects of Δ⁹-THC, while the PPARγ agonist pioglitazone resulted in protection from MPP+-induced neurotoxicity. Furthermore, Δ⁹-THC increased PPARγ expression in MPP+-treated SH-SY5Y cells, another indicator of PPARγ activation. We have demonstrated up-regulation of the CB1 receptor in direct response to neuronal injury in a human PD cell culture model, and a direct neuronal protective effect of Δ⁹-THC that may be mediated through PPARγ activation. © 2011 The Authors. Neuropathology and Applied Neurobiology © 2011 British Neuropathological

  5. Poly[3-(3, 4-dihydroxyphenyl) glyceric acid] from Comfrey exerts anti-cancer efficacy against human prostate cancer via targeting androgen receptor, cell cycle arrest and apoptosis.

    Shrotriya, Sangeeta; Gagan, Deep; Ramasamy, Kumaraguruparan; Raina, Komal; Barbakadze, Vakhtang; Merlani, Maia; Gogilashvili, Lali; Amiranashvili, Lela; Mulkijanyan, Karen; Papadopoulos, Kyriakos; Agarwal, Chapla; Agarwal, Rajesh

    2012-08-01

    The major obstacles in human prostate cancer (PCA) treatment are the development of resistance to androgen ablation therapy leading to hormone-refractory state and the toxicity associated with chemotherapeutic drugs. Thus, the identification of additional non-toxic agents that are effective against both androgen-dependent and androgen-independent PCA is needed. In the present study, we investigated the efficacy of a novel phytochemical poly[3-(3, 4-dihydroxyphenyl)glyceric acid] (p-DGA) from Caucasian species of comfrey (Symphytum caucasicum) and its synthetic derivative syn-2, 3-dihydroxy-3-(3, 4-dihydroxyphenyl) propionic acid (m-DGA) against PCA LNCaP and 22Rv1 cells. We found that both p-DGA and m-DGA suppressed the growth and induced death in PCA cells, with comparatively lesser cytotoxicity towards non-neoplastic human prostate epithelial cells. Furthermore, we also found that both p-DGA and m-DGA caused G(1) arrest in PCA cells through modulating the expression of cell cycle regulators, especially an increase in CDKIs (p21 and p27). In addition, p-DGA and m-DGA induced apoptotic death by activating caspases, and also strongly decreased AR and PSA expression. Consistent with in vitro results, our in vivo study showed that p-DGA feeding strongly inhibited 22Rv1 tumors growth by 76% and 88% at 2.5 and 5mg/kg body weight doses, respectively, without any toxicity, together with a strong decrease in PSA level in plasma; and a decrease in PCNA, AR and PSA expression but increase in p21/p27 expression and apoptosis in tumor tissues from p-DGA-fed mice. Overall, present study identifies p-DGA as a potent agent against PCA without any toxicity, and supports its clinical application.

  6. The HDAC Inhibitors Scriptaid and LBH589 Combined with the Oncolytic Virus Delta24-RGD Exert Enhanced Anti-Tumor Efficacy in Patient-Derived Glioblastoma Cells.

    Lotte M E Berghauser Pont

    Full Text Available A phase I/II trial for glioblastoma with the oncolytic adenovirus Delta24-RGD was recently completed. Delta24-RGD conditionally replicates in cells with a disrupted retinoblastoma-pathway and enters cells via αvβ3/5 integrins. Glioblastomas are differentially sensitive to Delta24-RGD. HDAC inhibitors (HDACi affect integrins and share common cell death pathways with Delta24-RGD. We studied the combination treatment effects of HDACi and Delta24-RGD in patient-derived glioblastoma stem-like cells (GSC, and we determined the most effective HDACi.SAHA, Valproic Acid, Scriptaid, MS275 and LBH589 were combined with Delta24-RGD in fourteen distinct GSCs. Synergy was determined by Chou Talalay method. Viral infection and replication were assessed using luciferase and GFP encoding vectors and hexon-titration assays. Coxsackie adenovirus receptor and αvβ3 integrin levels were determined by flow cytometry. Oncolysis and mechanisms of cell death were studied by viability, caspase-3/7, LDH and LC3B/p62, phospho-p70S6K. Toxicity was studied on normal human astrocytes. MGMT promotor methylation status, TCGA classification, Rb-pathway and integrin gene expression levels were assessed as markers of responsiveness.Scriptaid and LBH589 acted synergistically with Delta24-RGD in approximately 50% of the GSCs. Both drugs moderately increased αvβ3 integrin levels and viral infection in responding but not in non-responding GSCs. LBH589 moderately increased late viral gene expression, however, virus titration revealed diminished viral progeny production by both HDACi, Scriptaid augmented caspase-3/7 activity, LC3B conversion, p62 and phospho-p70S6K consumption, as well as LDH levels. LBH589 increased LDH and phospho-p70S6K consumption. Responsiveness correlated with expression of various Rb-pathway genes and integrins. Combination treatments induced limited toxicity to human astrocytes.LBH589 and Scriptaid combined with Delta24-RGD revealed synergistic anti

  7. The cytoskeletal inhibitors latrunculin A and blebbistatin exert antitumorigenic properties in human hepatocellular carcinoma cells by interfering with intracellular HuR trafficking

    Doller, Anke; Badawi, Amel [Pharmazentrum Frankfurt/ZAFES, Klinikum der Goethe-Universität Frankfurt, Frankfurt/Main (Germany); Schmid, Tobias; Brauß, Thilo [Institut für Biochemie I (Pathobiochemie), Klinikum der Goethe-Universität Frankfurt, Frankfurt/Main (Germany); Pleli, Thomas [Medizinische Klinik 1, Schwerpunkt Gastroenterologie und Hepatologie, Klinikum der Goethe-Universität Frankfurt, Frankfurt/Main (Germany); Meyer zu Heringdorf, Dagmar [Pharmazentrum Frankfurt/ZAFES, Klinikum der Goethe-Universität Frankfurt, Frankfurt/Main (Germany); Piiper, Albrecht [Medizinische Klinik 1, Schwerpunkt Gastroenterologie und Hepatologie, Klinikum der Goethe-Universität Frankfurt, Frankfurt/Main (Germany); Pfeilschifter, Josef [Pharmazentrum Frankfurt/ZAFES, Klinikum der Goethe-Universität Frankfurt, Frankfurt/Main (Germany); Eberhardt, Wolfgang, E-mail: w.eberhardt@em.uni-frankfurt.de [Pharmazentrum Frankfurt/ZAFES, Klinikum der Goethe-Universität Frankfurt, Frankfurt/Main (Germany)

    2015-01-01

    The impact of the RNA-binding protein HuR for the post-transcriptional deregulation of tumor-relevant genes is well established. Despite of elevations in HuR expression levels, an increase in cytoplasmic HuR abundance in many cases correlates with a high grade of malignancy. Here, we demonstrated that administration of the actin-depolymerizing macrolide latrunculin A, or blebbistatin, an inhibitor of myosin II ATPase activity, caused a dose- and time-dependent reduction in the high cytoplasmic HuR content of HepG2 and Huh7 hepatocellular carcinoma (HCC) cells. Subcellular fractionation revealed that in addition, both inhibitors strongly attenuated cytoskeletal and membrane-bound HuR abundance and conversely increased the HuR amount in nuclear cell fractions. Concomitant with changes in intracellular HuR localization, both cytoskeletal inhibitors markedly decreased the half-lives of cyclooxygenase-2 (COX-2), cyclin A and cyclin D{sub 1} encoding mRNAs resulting in a significant reduction in their expression levels in HepG2 cells. Importantly, a similar reduction in the expression of these HuR targets was achieved by a RNA interference (RNAi)-mediated knockdown of either HuR or nonmuscle myoin IIA. Using polysomal fractionation, we further demonstrate that the decrease in cytoplasmic HuR by latrunculin A or blebbistatin is accompanied by a marked change in the allocation of HuR and its mRNA cargo from polysomes to ribonucleoprotein (RNP) particles. Functionally, the basal migration and prostaglandin E{sub 2} synthesis are similarly impaired in inhibitor-treated and stable HuR-knockdown HepG2 cells. Our data demonstrate that interfering with the actomyosin-dependent HuR trafficking may comprise a valid therapeutic option for antagonizing pathologic posttranscriptional gene expression by HuR and furthermore emphasize the potential benefit of HuR inhibitory strategies for treatment of HCC. - Highlights: • We tested the effects of latrunculin A and blebbistatin on

  8. The cytoskeletal inhibitors latrunculin A and blebbistatin exert antitumorigenic properties in human hepatocellular carcinoma cells by interfering with intracellular HuR trafficking

    Doller, Anke; Badawi, Amel; Schmid, Tobias; Brauß, Thilo; Pleli, Thomas; Meyer zu Heringdorf, Dagmar; Piiper, Albrecht; Pfeilschifter, Josef; Eberhardt, Wolfgang

    2015-01-01

    The impact of the RNA-binding protein HuR for the post-transcriptional deregulation of tumor-relevant genes is well established. Despite of elevations in HuR expression levels, an increase in cytoplasmic HuR abundance in many cases correlates with a high grade of malignancy. Here, we demonstrated that administration of the actin-depolymerizing macrolide latrunculin A, or blebbistatin, an inhibitor of myosin II ATPase activity, caused a dose- and time-dependent reduction in the high cytoplasmic HuR content of HepG2 and Huh7 hepatocellular carcinoma (HCC) cells. Subcellular fractionation revealed that in addition, both inhibitors strongly attenuated cytoskeletal and membrane-bound HuR abundance and conversely increased the HuR amount in nuclear cell fractions. Concomitant with changes in intracellular HuR localization, both cytoskeletal inhibitors markedly decreased the half-lives of cyclooxygenase-2 (COX-2), cyclin A and cyclin D 1 encoding mRNAs resulting in a significant reduction in their expression levels in HepG2 cells. Importantly, a similar reduction in the expression of these HuR targets was achieved by a RNA interference (RNAi)-mediated knockdown of either HuR or nonmuscle myoin IIA. Using polysomal fractionation, we further demonstrate that the decrease in cytoplasmic HuR by latrunculin A or blebbistatin is accompanied by a marked change in the allocation of HuR and its mRNA cargo from polysomes to ribonucleoprotein (RNP) particles. Functionally, the basal migration and prostaglandin E 2 synthesis are similarly impaired in inhibitor-treated and stable HuR-knockdown HepG2 cells. Our data demonstrate that interfering with the actomyosin-dependent HuR trafficking may comprise a valid therapeutic option for antagonizing pathologic posttranscriptional gene expression by HuR and furthermore emphasize the potential benefit of HuR inhibitory strategies for treatment of HCC. - Highlights: • We tested the effects of latrunculin A and blebbistatin on different Hu

  9. Cerebral av angiomas: 3-dimensional demonstration by spiral CT

    Rieger, J.; Hosten, N.; Neumann, K.; Lemke, A.J.; Langer, R.; Lanksch, W.R.; Pfeifer, K.J.; Felix, R.

    1994-01-01

    In 20 patients with known or suspected supratentorial arteriovenous malformations, an attempt was made to see how far CT angiography with 3-dimensional reconstructions is able to make a diagnosis and to differentiate the various components of the angioma. Spiral CT was performed following an intravenous bolus injection of 60-80 ml of iodine containing contrast medium. In all patients the diagnosis was confirmed by intra-arterial DSA of the vertebral vessels. In 13 patients, av malformations could be diagnosed following multiplanar 3-D reconstructions which agreed with the findings on DSA. The large supplying vessels, the nidus and the large draining veins could be defined with certainty. In 6 patients follow-up examination after embolisation was performed. The results could be demonstrated in three dimensions and the success of treatment could be documented unequivocally. CT angiography with 3-D reconstruction is able to supply important information in the majority of intracranial av malformations, both during initial investigation and following treatment. (orig.) [de

  10. A 3-Dimensional Atlas of Human Tongue Muscles

    SANDERS, IRA; MU, LIANCAI

    2013-01-01

    The human tongue is one of the most important yet least understood structures of the body. One reason for the relative lack of research on the human tongue is its complex anatomy. This is a real barrier to investigators as there are few anatomical resources in the literature that show this complex anatomy clearly. As a result, the diagnosis and treatment of tongue disorders lags behind that for other structures of the head and neck. This report intended to fill this gap by displaying the tongue’s anatomy in multiple ways. The primary material used in this study was serial axial images of the male and female human tongue from the Visible Human (VH) Project of the National Library of Medicine. In addition, thick serial coronal sections of three human tongues were rendered translucent. The VH axial images were computer reconstructed into serial coronal sections and each tongue muscle was outlined. These outlines were used to construct a 3-dimensional computer model of the tongue that allows each muscle to be seen in its in vivo anatomical position. The thick coronal sections supplement the 3-D model by showing details of the complex interweaving of tongue muscles throughout the tongue. The graphics are perhaps the clearest guide to date to aid clinical or basic science investigators in identifying each tongue muscle in any part of the human tongue. PMID:23650264

  11. A monoclonal IgM directed against immunodominant catalase B of cell wall of Aspergillus fumigatus exerts anti-A. fumigatus activities.

    Chaturvedi, Ashok K; Kumar, Rohitashw; Kumar, Awanit; Shukla, Praveen K

    2009-11-01

    Aspergillus fumigatus, a ubiquitous fungus, has been reported to cause human diseases like allergic pulmonary aspergillosis, aspergilloma and invasive infection. Limited spectrum and emergence of resistance has become a serious problem with available antifungals. Therefore, an alternative approach is required for successful treatment of mycoses. In the present study, immunogenic protein profile of A. fumigatus cell wall was generated using two-dimensional-gel electrophoresis and three hybridomas producing monoclonal antibodies (MAbs; IgM) were selected after fusion experiments. Of these three MAbs, MAb-7 exhibited potent in vitro inhibitory activity, which was confirmed by MTT assay, fluorescence-activated cell sorter analysis and immuno-fluorescence studies, and the protein was identified as catalase B using MALDI-TOF-MS.

  12. Chlorogenic acid complex (CGA7, standardized extract from green coffee beans exerts anticancer effects against cultured human colon cancer HCT-116 cells

    K. Gouthamchandra

    2017-09-01

    Full Text Available Coffee is commonly consumed beverage in the world and it has been suggested to have beneficial effect. Chlorogenic acids (CGAs are main ingredient of coffee beans which has been extensively used in nutraceuticals and medicine. Recently, various therapeutic effects of chlorogenic acids have been investigated. However, there are limited studies to investigate its anticancer properties. In the present study, we have used chlorogenic acid complex (CGA7 a decaffeinated water soluble green coffee bean extract to evaluate its cytotoxic effect on human and mouse cancer cell lines by using different approaches. From our results we found CGA7 treatment induces cell death in a dose and time dependent manner in different cancer cell lines. Further, CGA7 induced apoptosis was characterized by DNA fragmentation, PARP-1 cleavage, caspase-9 activation, and down regulation of Bcl-2, an anti-apoptotic protein and up regulation of pro-apoptotic protein BAX. Overall findings indicated that CGA7 complex a potent anticancer molecule found in green coffee beans could be a safe bioactive ingredient for prevention of cancer.

  13. Compounds isolated from the aerial part of Crataegus azarolus inhibit growth of B16F10 melanoma cells and exert a potent inhibition of the melanin synthesis.

    Mustapha, Nadia; Bzéouich, Imèn Mokdad; Ghedira, Kamel; Hennebelle, Thierry; Chekir-Ghedira, Leila

    2015-02-01

    Poor therapeutic results have been reported for treatment of malignant melanoma; therefore in this study, we have investigated inhibitory capacity of vitexin-2''-O-rhamnoside as well as the extract from which it was isolated, i.e. the ethyl acetate extract obtained from the leaves of Crataegus azarolus, on mouse melanoma (B16F10) proliferation. Cell viability was determined using the 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. In addition, amounts of melanin and tyrosinase were measured spectrophotometrically at 475nm. Ethyl acetate extract and vitexin-2''-O-rhamnoside exhibited significant anti-proliferative activity against B16F10 melanoma cells after incubation for 48hours with IC50s of 50μg/mL and 20μM, respectively. Furthermore, these two compounds have the ability to reduce the melanin content by inhibiting the tyrosinase activity of B16F10 cells. Thus, further investigations are merited to ascertain their potential application in treating hyperpigmentation disorders. Copyright © 2014. Published by Elsevier Masson SAS.

  14. Low-molecular-weight fucoidan and high-stability fucoxanthin from brown seaweed exert prebiotics and anti-inflammatory activities in Caco-2 cells

    Pai-An Hwang

    2016-08-01

    Full Text Available Background: The aim of this study is to investigate the anti-inflammatory effects of low-molecular-weight fucoidan (LMF and high-stability fucoxanthin (HS-Fucox in a lipopolysaccharide-induced inflammatory Caco-2 cell line co-culture with B. lactis. Methods: We used various methods such as transepithelial resistance (TER assay, cytokine secretion assay, and tight junction protein mRNA expression assay to examine LMF and HS-Fucox anti-inflammatory properties. Results: LMF and HS-Fucox activated probiotic growth and reduced the inflammation of the intestinal epithelial cells. Moreover, the combination of LMFHS-Fucox dramatically enhanced the intestinal epithelial barrier and immune function against the lipopolysaccharide effect by inhibiting IL-1β and TNF-α and promoting IL-10 and IFN-γ. Conclusion: These findings suggested that LMF and HS-Fucox, alone or in combination, could be the potential natural compounds to enhance the immune system and have an anti-inflammatory effect on the intestinal cells.

  15. Casein Glycomacropeptide Hydrolysates Exert Cytoprotective Effect against Cellular Oxidative Stress by Up-Regulating HO-1 Expression in HepG2 Cells

    Tiange Li

    2017-01-01

    Full Text Available Oxidative stress is considered as an important mediator in the progression of metabolic disorders. The objective of this study was to investigate the potential hepatoprotective effects and mechanisms of bovine casein glycomacropeptide hydrolysates (GHP on hydrogen peroxide (H2O2-induced oxidative damage in HepG2 cells. Results showed that GHP significantly blocked H2O2-induced intracellular reactive oxygen species (ROS generation and cell viability reduction in a dose-dependent manner. Further, GHP concentration-dependently induced heme oxygenase-1 (HO-1 expression and increased nuclear factor-erythroid 2-related factor 2 (Nrf2 nuclear translocation. Moreover, pretreatment of GHP increased the activation of p38 mitogen-activated protein kinase (p38 MAPK and extracellular signal-regulated protein kinase 1/2 (ERK1/2, which were shown to contribute to Nrf2-mediated HO-1 expression. Taken together, GHP protected HepG2 cells from oxidative stress by activation of Nrf2 and HO-1 via p38 MAPK and ERK1/2 signaling pathways. Our findings indicate that bovine casein glycomacropeptide hydrolysates might be a potential ingredient in the treatment of oxidative stress-related disorders and further studies are needed to investigate the protective effects in vivo.

  16. Shen-Qi-Jie-Yu-Fang exerts effects on a rat model of postpartum depression by regulating inflammatory cytokines and CD4+CD25+ regulatory T cells

    Li JY

    2016-04-01

    Full Text Available Jingya Li,1,* Ruizhen Zhao,1,* Xiaoli Li,1 Wenjun Sun,1 Miao Qu,1 Qisheng Tang,1 Xinke Yang,1 Shujing Zhang2 1Third Affiliated Hospital, 2School of Basic Medical Sciences, Beijing University of Chinese Medicine, Beijing, People’s Republic of China *These authors contributed equally to this work Background: Shen-Qi-Jie-Yu-Fang (SJF is composed of eight Chinese medicinal herbs. It is widely used in traditional Chinese medicine for treating postpartum depression (PPD. Previous studies have shown that SJF treats PPD through the neuroendocrine mechanism. Aim: To further investigate the effect of SJF on the immune system, including the inflammatory response system and CD4+CD25+ regulatory T (Treg cells. Materials and methods: Sprague Dawley rats were used to create an animal model of PPD by inducing hormone-simulated pregnancy followed by hormone withdrawal. After hormone withdrawal, the PPD rats were treated with SJF or fluoxetine for 1, 2, and 4 weeks. Levels of Treg cells in peripheral blood were measured by flow cytometry analysis. Serum interleukin (IL-1β and IL-6 were evaluated by enzyme-linked immunosorbent assay, and gene and protein expressions of IL-1RI, IL-6Rα, and gp130 in the hippocampus were observed by reverse-transcription polymerase chain reaction and Western blot. Results: Serum IL-1β in PPD rats increased at 2 weeks and declined from then on, while serum IL-6 increased at 1, 2, and 4 weeks. Both IL-1β and IL-6 were downregulated by SJF and fluoxetine. Changes in gene and protein expressions of IL-1RI and gp130 in PPD rats were consistent with changes in serum IL-1β, and were able to be regulated by SJF and fluoxetine. The levels of Treg cells were negatively correlated with serum IL-1β and IL-6, and were decreased in PPD rats. The levels of Treg cells were increased by SJF and fluoxetine. Conclusion: Dysfunction of proinflammatory cytokines and Tregs in different stages of PPD was attenuated by SJF and fluoxetine through

  17. Di-2-pyridylhydrazone Dithiocarbamate Butyric Acid Ester Exerted Its Proliferative Inhibition against Gastric Cell via ROS-Mediated Apoptosis and Autophagy

    Xingshuang Guo

    2018-01-01

    Full Text Available Diversified biological activities of dithiocarbamates have attracted widespread attention; improving their feature or exploring their potent action of mechanism is a hot topic in medicinal research. Herein, we presented a study on synthesis and investigation of a novel dithiocarbamate, DpdtbA (di-2-pyridylhydrazone dithiocarbamate butyric acid ester, on antitumor activity. The growth inhibition assay revealed that DpdtbA had important antitumor activity for gastric cancer (GC cell lines (IC50 = 4.2 ± 0.52 μM for SGC-7901, 3.80 ± 0.40 μM for MGC-803. The next study indicated that growth inhibition is involved in ROS generation in mechanism; accordingly, the changes in mitochondrial membrane permeability, apoptotic genes, cytochrome c, bax, and bcl-2 were observed, implying that the growth inhibition of DpdtbA is involved in ROS-mediated apoptosis. On the other hand, the upregulated p53 upon DpdtbA treatment implied that p53 could also mediate the apoptosis. Yet the excess generation of ROS induced by DpdtbA led to cathepsin D translocation and increase of autophagic vacuoles and LC3-II, demonstrating that autophagy was also a contributor to growth inhibition. Further investigation showed that DpdtbA could induce cell cycle arrest at the G1 phase. This clearly indicated the growth inhibition of DpdtbA was via triggering ROS formation and evoking p53 response, consequently leading to alteration in gene expressions that are related to cell survival.

  18. N‑trans‑ρ‑caffeoyl tyramine isolated from Tribulus terrestris exerts anti‑inflammatory effects in lipopolysaccharide‑stimulated RAW 264.7 cells.

    Ko, Han-Jik; Ahn, Eun-Kyung; Oh, Joa Sub

    2015-10-01

    Inflammation is induced by the expression of cyclooxygenase‑2 (COX‑2), which is an important mediator of chronic inflammatory diseases, such as rheumatoid arthritis, asthma and inflammatory bowel disease. Tribulus terrestris (T. terrestris) is known to have a beneficial effect on inflammatory diseases. In this study, we investigated the effects of N‑trans‑ρ‑caffeoyl tyramine (CT) isolated from T. terrestris on the production of nitric oxide (NO), and the expression of pro‑inflammatory cytokines and COX‑2 in lipopolysaccharide (LPS)‑stimulated RAW 264.7 cells. We also aimed to elucidate the molecular mechanisms involved. We found that the ethanolic extract of T. terrestris (EETT) and CT inhibited the production of NO, tumor necrosis factor‑α (TNF‑α), interleukin (IL)‑6 and IL‑10 in the LPS‑stimulated RAW 264.7 cells in a dose‑dependent manner. They were determined by reverse transcription-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA). In addition, CT markedly suppressed the expression of COX‑2 and the production of prostaglandin E2 (PGE2) in response to LPS stimulation. Furthermore, CT markedly decreased p‑c‑Jun N‑terminal kinase (p‑JNK) protein expression in LPS‑stimulated RAW 264.7 cells. COX-2 and p-JNK were measured by western blot analysis. Taken together, these findings indicate that CT isolated from T. terrestris is a novel and potent modulator of inflammatory responses. Thus, it may prove benefiical to further evaluate CT as a possible treatment for chronic inflammatory diseases.

  19. Progesterone and estradiol exert an inhibitory effect on the production of anti-inflammatory cytokine IL-10 by activated MZ B cells.

    Bommer, I; Muzzio, D O; Zygmunt, M; Jensen, F

    2016-08-01

    The main message of this work is the fact that female sex hormones, progesterone and estradiol, whose levels significantly rise during pregnancy, inhibit the production of anti-inflammatory cytokine IL-10 with no apparent effect on pro-inflammatory cytokine TNF-α by activated MZ B cells. This is an important piece of information and helps to better understand how the maternal immune system controls the balance between immune tolerance and immune activation during pregnancy leading to the simultaneously acceptance of the semi-allogeneic fetus and the proper defense of the mother against pathogens during this critical period of time. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  20. Isthmin exerts pro-survival and death-promoting effect on endothelial cells through alphavbeta5 integrin depending on its physical state.

    Zhang, Y; Chen, M; Venugopal, S; Zhou, Y; Xiang, W; Li, Y-H; Lin, Q; Kini, R M; Chong, Y-S; Ge, R

    2011-05-05

    Isthmin (ISM) is a 60 kDa secreted-angiogenesis inhibitor that suppresses tumor growth in mouse and disrupts vessel patterning in zebrafish embryos. It selectively binds to alphavbeta5 (αvβ5) integrin on the surface of endothelial cells (ECs), but the mechanism of its antiangiogenic action remains unknown. In this work, we establish that soluble ISM suppresses in vitro angiogenesis and induces EC apoptosis by interacting with its cell surface receptor αvβ5 integrin through a novel 'RKD' motif localized within its adhesion-associated domain in MUC4 and other proteins domain. ISM induces EC apoptosis through integrin-mediated death (IMD) by direct recruitment and activation of caspase-8 without causing anoikis. On the other hand, immobilized ISM loses its antiangiogenic function and instead promotes EC adhesion, survival and migration through αvβ5 integrin by activating focal adhesion kinase (FAK). ISM unexpectedly has both a pro-survival and death-promoting effect on ECs depending on its physical state. This dual function of a single antiangiogenic protein may impact its antiangiogenic efficacy in vivo.

  1. Individualized Physical 3-dimensional Kidney Tumor Models Constructed From 3-dimensional Printers Result in Improved Trainee Anatomic Understanding.

    Knoedler, Margaret; Feibus, Allison H; Lange, Andrew; Maddox, Michael M; Ledet, Elisa; Thomas, Raju; Silberstein, Jonathan L

    2015-06-01

    To evaluate the effect of 3-dimensionally (3D) printed physical renal models with enhancing masses on medical trainee characterization, localization, and understanding of renal malignancy. Proprietary software was used to import standard computed tomography (CT) cross-sectional imaging into 3D printers to create physical models of renal units with enhancing renal lesions in situ. Six different models were printed from a transparent plastic resin; the normal parenchyma was printed in a clear, translucent plastic, with a red hue delineating the suspicious renal lesion. Medical students, who had completed their first year of training, were given an overview and tasked with completion of RENAL nephrometry scores, separately using CT imaging and 3D models. Trainees were also asked to complete a questionnaire about their experience. Variability between trainees was assessed by intraclass correlation coefficients (ICCs), and kappa statistics were used to compare the trainee to experts. Overall trainee nephrometry score accuracy was significantly improved with the 3D model vs CT scan (P renal mass. Physical 3D models using readily available printing techniques improve trainees' understanding and characterization of individual patients' enhancing renal lesions. Published by Elsevier Inc.

  2. The small FOXP1 isoform predominantly expressed in activated B cell-like diffuse large B-cell lymphoma and full-length FOXP1 exert similar oncogenic and transcriptional activity in human B cells.

    van Keimpema, Martine; Grüneberg, Leonie J; Schilder-Tol, Esther J M; Oud, Monique E C M; Beuling, Esther A; Hensbergen, Paul J; de Jong, Johann; Pals, Steven T; Spaargaren, Marcel

    2017-03-01

    The forkhead transcription factor FOXP1 is generally regarded as an oncogene in activated B cell-like diffuse large B-cell lymphoma. Previous studies have suggested that a small isoform of FOXP1 rather than full-length FOXP1, may possess this oncogenic activity. Corroborating those studies, we herein show that activated B cell-like diffuse large B-cell lymphoma cell lines and primary activated B cell-like diffuse large B-cell lymphoma cells predominantly express a small FOXP1 isoform, and that the 5'-end of the Foxp1 gene is a common insertion site in murine lymphomas in leukemia virus- and transposon-mediated insertional mutagenesis screens. By combined mass spectrometry, (quantative) reverse transcription polymerase chain reaction/sequencing, and small interfering ribonucleic acid-mediated gene silencing, we determined that the small FOXP1 isoform predominantly expressed in activated B cell-like diffuse large B-cell lymphoma lacks the N-terminal 100 amino acids of full-length FOXP1. Aberrant overexpression of this FOXP1 isoform (ΔN100) in primary human B cells revealed its oncogenic capacity; it repressed apoptosis and plasma cell differentiation. However, no difference in potency was found between this small FOXP1 isoform and full-length FOXP1. Furthermore, overexpression of full-length FOXP1 or this small FOXP1 isoform in primary B cells and diffuse large B-cell lymphoma cell lines resulted in similar gene regulation. Taken together, our data indicate that this small FOXP1 isoform and full-length FOXP1 have comparable oncogenic and transcriptional activity in human B cells, suggesting that aberrant expression or overexpression of FOXP1, irrespective of the specific isoform, contributes to lymphomagenesis. These novel insights further enhance the value of FOXP1 for the diagnostics, prognostics, and treatment of diffuse large B-cell lymphoma patients. Copyright© Ferrata Storti Foundation.

  3. Distance stereotest using a 3-dimensional monitor for adult subjects.

    Kim, Jongshin; Yang, Hee Kyung; Kim, Youngmin; Lee, Byoungho; Hwang, Jeong-Min

    2011-06-01

    To evaluate the validity and test-retest reliability of a contour-based 3-dimensional (3-D) monitor distance stereotest (distance 3-D stereotest) and to measure the maximum horizontal disparity that can be fused with disparity vergence for determining the largest measurable disparity of true stereopsis. Observational case series. Sixty-four normal adult subjects (age range, 23 to 39 years) were recruited. Contour-based circles (crossed disparity, 5000 to 20 seconds of arc; Microsoft Visual Studio C(++) 6.0; Microsoft, Inc, Seattle, Washington, USA) were generated on a 3-D monitor (46-inch stereoscopic display) using polarization glasses and were presented to subjects with normal binocularity at 3 m. While the position of the stimulus changed among 4 possible locations, the subjects were instructed to press the corresponding position of the stimulus on a keypad. The results with the new distance 3-D stereotest were compared with those from the distance Randot stereotest. The results of the distance 3-D stereotest and the distance Randot stereotests were identical in 64% and within 1 disparity level in 97% of normal adults. Scores obtained with the 2 tests showed a statistically significant correlation (r = 0.324, P = .009). The half-width of the 95% limit of agreement was 0.47 log seconds of arc (1.55 octaves) using the distance 3-D stereotest--similar to or better than that obtained with conventional distance stereotests. The maximum binocular disparity that can be fused with vergence was 1828 ± 794 seconds of arc (range, 4000 to 500). The distance 3-D stereotest showed good concordance with the distance Randot stereotest and relatively good test-retest reliability, supporting the validity of the distance 3-D stereotest. The normative data set obtained from the present study can serve as a useful reference for quantitative assessment of a wide range of binocular sensory abnormalities. Copyright © 2011 Elsevier Inc. All rights reserved.

  4. The 3-dimensional construction of the Rae craton, central Canada

    Snyder, David B.; Craven, James A.; Pilkington, Mark; Hillier, Michael J.

    2015-10-01

    Reconstruction of the 3-dimensional tectonic assembly of early continents, first as Archean cratons and then Proterozoic shields, remains poorly understood. In this paper, all readily available geophysical and geochemical data are assembled in a 3-D model with the most accurate bedrock geology in order to understand better the geometry of major structures within the Rae craton of central Canada. Analysis of geophysical observations of gravity and seismic wave speed variations revealed several lithospheric-scale discontinuities in physical properties. Where these discontinuities project upward to correlate with mapped upper crustal geological structures, the discontinuities can be interpreted as shear zones. Radiometric dating of xenoliths provides estimates of rock types and ages at depth beneath sparse kimberlite occurrences. These ages can also be correlated to surface rocks. The 3.6-2.6 Ga Rae craton comprises at least three smaller continental terranes, which "cratonized" during a granitic bloom. Cratonization probably represents final differentiation of early crust into a relatively homogeneous, uniformly thin (35-42 km), tonalite-trondhjemite-granodiorite crust with pyroxenite layers near the Moho. The peak thermotectonic event at 1.86-1.7 Ga was associated with the Hudsonian orogeny that assembled several cratons and lesser continental blocks into the Canadian Shield using a number of southeast-dipping megathrusts. This orogeny metasomatized, mineralized, and recrystallized mantle and lower crustal rocks, apparently making them more conductive by introducing or concentrating sulfides or graphite. Little evidence exists of thin slabs similar to modern oceanic lithosphere in this Precambrian construction history whereas underthrusting and wedging of continental lithosphere is inferred from multiple dipping discontinuities.

  5. Development and Validation of a 3-Dimensional CFB Furnace Model

    Vepsäläinen, Arl; Myöhänen, Karl; Hyppäneni, Timo; Leino, Timo; Tourunen, Antti

    At Foster Wheeler, a three-dimensional CFB furnace model is essential part of knowledge development of CFB furnace process regarding solid mixing, combustion, emission formation and heat transfer. Results of laboratory and pilot scale phenomenon research are utilized in development of sub-models. Analyses of field-test results in industrial-scale CFB boilers including furnace profile measurements are simultaneously carried out with development of 3-dimensional process modeling, which provides a chain of knowledge that is utilized as feedback for phenomenon research. Knowledge gathered by model validation studies and up-to-date parameter databases are utilized in performance prediction and design development of CFB boiler furnaces. This paper reports recent development steps related to modeling of combustion and formation of char and volatiles of various fuel types in CFB conditions. Also a new model for predicting the formation of nitrogen oxides is presented. Validation of mixing and combustion parameters for solids and gases are based on test balances at several large-scale CFB boilers combusting coal, peat and bio-fuels. Field-tests including lateral and vertical furnace profile measurements and characterization of solid materials provides a window for characterization of fuel specific mixing and combustion behavior in CFB furnace at different loads and operation conditions. Measured horizontal gas profiles are projection of balance between fuel mixing and reactions at lower part of furnace and are used together with both lateral temperature profiles at bed and upper parts of furnace for determination of solid mixing and combustion model parameters. Modeling of char and volatile based formation of NO profiles is followed by analysis of oxidizing and reducing regions formed due lower furnace design and mixing characteristics of fuel and combustion airs effecting to formation ofNO furnace profile by reduction and volatile-nitrogen reactions. This paper presents

  6. Dioxin exerts anti-estrogenic actions in a novel dioxin-responsive telomerase-immortalized epithelial cell line of the porcine oviduct (TERT-OPEC).

    Hombach-Klonisch, Sabine; Pocar, Paola; Kauffold, Johannes; Klonisch, Thomas

    2006-04-01

    Oviduct epithelial cells are important for the nourishment and survival of ovulated oocytes and early embryos, and they respond to the steroid hormones estrogen and progesterone. Endocrine-disrupting polyhalogenated aromatic hydrocarbons (PHAH) are environmental toxins that act in part through the ligand-activated transcription factor arylhydrocarbon receptor (AhR; dioxin receptor), and exposure to PHAH has been shown to decrease fertility. To investigate effects of PHAHs on the oviduct epithelium as a potential target tissue of dioxin-type endocrine disruptors, we have established a novel telomerase-immortalized oviduct porcine epithelial cell line (TERT-OPEC). TERT-OPEC exhibited active telomerase and the immunoreactive epithelial marker cytokeratin but lacked the stromal marker vimentin. TERT-OPEC contained functional estrogen receptor (ER)-alpha and AhR, as determined by the detection of ER-alpha- and AhR-specific target molecules. Treatment of TERT-OPEC with the AhR ligand 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) resulted in a significant increase in the production of the cytochrome P-450 microsomal enzyme CYP1A1. Activated AhR caused a downregulation of ER nuclear protein fraction and significantly decreased ER-signaling in TERT-OPEC as determined by ERE-luciferase transient transfection assays. In summary, the TCDD-induced and AhR-mediated anti-estrogenic responses by TERT-OPEC suggest that PHAH affect the predominantly estrogen-dependent differentiation of the oviduct epithelium within the fallopian tube. This action then alters the local endocrine milieu, potentially resulting in a largely unexplored cause of impaired embryonic development and female infertility.

  7. Cytoprotective effect exerted by geraniin in HepG2 cells is through microRNA mediated regulation of BACH-1 and HO-1.

    Aayadi, Hoda; Mittal, Smriti P K; Deshpande, Anjali; Gore, Makarand; Ghaskadbi, Saroj S

    2017-11-01

    Geraniin, a hydrolysable tannin, used in traditional medicine in Southeast Asia, is known to exhibit various biological activities. As an antioxidant it is known to up-regulate phase II enzyme Heme oxygenase-1 (HO-1). However its mechanism is not clearly understood. Nuclear factor erythroid-derived 2 related factor 2 (Nrf-2) is transcriptionally up-regulated by Extracellular signal-regulated kinase (ERK) 1/2 and retained in nucleus due to inactivated Glycogen synthase kinase 3 beta (GSK-3β). Geraniin additionally down-regulates expression of microRNA 217 and 377 (miR-217 and miR-377) which target HO-1 mRNA. Expression of BTB and CNC homolog 1 (BACH-1), another regulator of HO-1, is also down-regulated by up-regulating microRNA 98 (miR-98), a negative regulator of BACH-1. Thus, geraniin up-regulates HO-1 expression both through activating its positive regulator Nrf-2 and by down-regulating its negative regulator BACH-1. Up-regulation of HO-1 also confers protection to HepG2 cells from tertiary butyl hydroperoxide (TBH) induced cytotoxicity. [BMB Reports 2017; 50(11): 560-565].

  8. Does mental exertion alter maximal muscle activation?

    Vianney eRozand

    2014-09-01

    Full Text Available Mental exertion is known to impair endurance performance, but its effects on neuromuscular function remain unclear. The purpose of this study was to test the hypothesis that mental exertion reduces torque and muscle activation during intermittent maximal voluntary contractions of the knee extensors. Ten subjects performed in a randomized order three separate mental exertion conditions lasting 27 minutes each: i high mental exertion (incongruent Stroop task, ii moderate mental exertion (congruent Stroop task, iii low mental exertion (watching a movie. In each condition, mental exertion was combined with ten intermittent maximal voluntary contractions of the knee extensor muscles (one maximal voluntary contraction every 3 minutes. Neuromuscular function was assessed using electrical nerve stimulation. Maximal voluntary torque, maximal muscle activation and other neuromuscular parameters were similar across mental exertion conditions and did not change over time. These findings suggest that mental exertion does not affect neuromuscular function during intermittent maximal voluntary contractions of the knee extensors.

  9. 3-Dimensional numerical simulation of sodium spray fire accidents in LMFBRs

    Zhang Bin; Zhu Jizhou; Han Lang

    2005-01-01

    In order to estimate and foresee the sequence of sodium spray fires that may occur in the liquid metal cooled fast breeder reactors (LMFBRs), this paper develops a program to analyze such sodium fire accidents. The present study gives a 3-dimensional numerical analysis code for sodium spray fires. The spatial distributions of gas temperature and chemical species concentrations in the cell that sodium spray fires happened are given. This paper gives detailed explanation of combustion models and heat transfer models that applied in the program. And the calculation procedure and method in solving the fluid field are narrated in detail. Good agreements of an overall transient behavior are obtained in a sodium spray combustion test analysis. The comparison between the analytical and experimental results shows that the program presented in this paper is creditable and reasonable for simulating the sodium spray fires. (author)

  10. Cell-free spent media obtained from Bifidobacterium bifidum and Bifidobacterium crudilactis grown in media supplemented with 3’-sialyllactose exert virulence modulation on intestinal pathogens

    Bondue Pauline

    2016-09-01

    Full Text Available Complex oligosaccharides from human milk (HMO possess an antimicrobial activity and can promote the growth of bifidobacteria such as Bifidobacterium bifidum and Bifidobacterium longum subsp. infantis. In addition, fermentation of carbohydrates by bifidobacteria can result in the production of metabolites presenting an antivirulence effect on several pathogenic bacteria. Whey is rich in complex bovine milk oligosaccharides (BMO structurally similar to HMO and B. crudilactis, a species of bovine origin, is able to metabolize some of those complex carbohydrates. This study focused on the ability of B. bifidum and B. crudilactis to grow in a culture medium supplemented in 3’-sialyllactose (3’SL as sole source of carbon, a main BMO encountered in cow milk. Next, the effects of cell-free spent media (CFSM were tested against virulence expression of Escherichia coli O157:H7 and Salmonella enterica serovar Typhimurium. Both strains were able to grow in presence of 3’SL, but B. crudilactis showed the best growth (7.92 ± 0.3 log cfu/ml compared to B. bifidum (6.84 ± 0.9 log cfu/ml. Then, CFSM were tested for their effects on virulence gene expression by ler and hilA promoter activity of luminescent mutants of E. coli and S. Typhimurium, respectively, and on wild type strains of E. coli O157:H7 and S. Typhimurium using RT-qPCR. All CFSM resulted in significant under expression of the ler and hilA genes for the luminescent mutants and ler (ratios of -15.4 and -8.1 respectively and qseA (ratios of -2.1 and -3.1 for the wild type strain of E. coli O157:H7. The 3’SL, a major BMO, combined with some bifidobacteria strains of bovine or human origin could therefore be an interesting synbiotic to maintain or restore the intestinal health of young children. These effects observed in vitro will be further investigated regarding the exact nature of the active molecules.

  11. iRoot FM exerts an antibacterial effect on Porphyromonas endodontalis and improves the properties of stem cells from the apical papilla.

    Bi, J; Liu, Y; Liu, X M; Jiang, L M; Chen, X

    2018-03-07

    To investigate the antibacterial activity of a novel intracanal medicament, iRoot FM, against Porphyromonas endodontalis and its effects on the proliferation and osteo-/odontogenic differentiation of stem cells from apical papilla (SCAP). The agar diffusion test was used to compare the antimicrobial efficacy of iRoot FM with two traditional intracanal medicaments, calcium hydroxide [Ca(OH) 2 ] and triple antibiotic paste (TAP). The CCK-8 assay was used to assess the proliferation rate of SCAP when exposed to the three intracanal medicaments. The expression levels of ALP and DMP-1 and the capacity to form mineralized nodules were used to evaluate the osteo-/odontogenic differentiation of SCAP, as assessed by real-time PCR, Western blotting and alizarin red S staining. Data were statistically analysed with one-way analysis of variance (anova), and comparisons between each of two groups were analysed by the least significance difference method. P values less than 0.05 were considered statistically significant. The zone of inhibition against P. endodontalis produced by iRoot FM was 20.74 ± 4.35 mm, whilst the zones of inhibition of Ca(OH) 2 and TAP were 24.89 ± 3.84 mm and 34.51 ± 1.20 mm. The antibacterial capacity of iRoot FM was similar to that of Ca(OH) 2 (P > 0.05). SCAP, cultured in conditioned medium with iRoot FM, was associated with greater proliferation and osteo-/odontogenic differentiation capacity than those cultured in conditioned medium with Ca(OH) 2 and TAP (P endodontalis and could improve the proliferation and differentiation of SCAP. The findings provide evidence that iRoot FM has potential as an intracanal medicament for endodontic procedures in immature permanent teeth. © 2018 International Endodontic Journal. Published by John Wiley & Sons Ltd.

  12. Registration of 3-dimensional facial photographs for clinical use.

    Maal, Thomas J J; van Loon, Bram; Plooij, Joanneke M; Rangel, Frits; Ettema, Anke M; Borstlap, Wilfred A; Bergé, Stefaan J

    2010-10-01

    To objectively evaluate treatment outcomes in oral and maxillofacial surgery, pre- and post-treatment 3-dimensional (3D) photographs of the patient's face can be registered. For clinical use, it is of great importance that this registration process is accurate (photographs were captured at 3 different times: baseline (T(0)), after 1 minute (T(1)), and 3 weeks later (T(2)). Furthermore, a 3D photograph of the volunteer laughing (T(L)) was acquired to investigate the effect of facial expression. Two different registration methods were used to register the photographs acquired at all different times: surface-based registration and reference-based registration. Within the surface-based registration, 2 different software packages (Maxilim [Medicim NV, Mechelen, Belgium] and 3dMD Patient [3dMD LLC, Atlanta, GA]) were used to register the 3D photographs acquired at the various times. The surface-based registration process was repeated with the preprocessed photographs. Reference-based registration (Maxilim) was performed twice by 2 observers investigating the inter- and intraobserver error. The mean registration errors are small for the 3D photographs at rest (0.39 mm for T(0)-T(1) and 0.52 mm for T(0)-T(2)). The mean registration error increased to 1.2 mm for the registration between the 3D photographs acquired at T(0) and T(L). The mean registration error for the reference-based method was 1.0 mm for T(0)-T(1), 1.1 mm for T(0)-T(2), and 1.5 mm for T(0) and T(L). The mean registration errors for the preprocessed photographs were even smaller (0.30 mm for T(0)-T(1), 0.42 mm for T(0)-T(2), and 1.2 mm for T(0) and T(L)). Furthermore, a strong correlation between the results of both software packages used for surface-based registration was found. The intra- and interobserver error for the reference-based registration method was found to be 1.2 and 1.0 mm, respectively. Surface-based registration is an accurate method to compare 3D photographs of the same individual at

  13. Juglans regia Hexane Extract Exerts Antitumor Effect, Apoptosis ...

    Original Research Article. Juglans regia Hexane Extract Exerts Antitumor Effect,. Apoptosis Induction and Cell Circle Arrest in Prostate. Cancer Cells In vitro. Wei Li1, De-Yuan Li2*, ... composition of walnut is juglone (5-hydroxy-1, 4- naphthoquinone), the .... extract was confirmed by studying apoptotic body formation using ...

  14. Vitamins K2, K3 and K5 exert in vivo antitumor effects on hepatocellular carcinoma by regulating the expression of G1 phase-related cell cycle molecules.

    Kuriyama, Shigeki; Hitomi, Misuzu; Yoshiji, Hitoshi; Nonomura, Takako; Tsujimoto, Tatsuhiro; Mitoro, Akira; Akahane, Takami; Ogawa, Mutsumi; Nakai, Seiji; Deguchi, Akihiro; Masaki, Tsutomu; Uchida, Naohito

    2005-08-01

    A number of studies have shown that various vitamins K, specifically vitamin K2, possessed antitumor activity on various types of rodent- and human-derived neoplastic cell lines. However, there are only a small number of reports demonstrating in vivo antitumor effects of vitamins K. Furthermore, the mechanism of antitumor effects of vitamins K still remains to be examined. In the present study, we examined the antitumor effects of vitamins K2, K3 and K5 on PLC/PRF/5 human hepatocellular carcinoma (HCC) cells in vivo. Furthermore, to examine the mechanism of antitumor actions of these vitamins K, mRNA expression levels of various G1 phase-related cell cycle molecules were evaluated by using a real-time reverse transcription-polymerase chain reaction (RT-PCR) method. HCC-bearing animals were produced by implanting PLC/PRF/5 cells subcutaneously into athymic nude mice, and drinking water containing vitamin K2, K3 or K5 was given to the animals. Treatments with vitamins K2, K3 and K5 were shown to markedly inhibit the growth of HCC tumors. To examine the mechanism of in vivo antitumor effects of vitamins K, total RNA was extracted from HCC tumors, and the expression of G1 phase-related cell cycle molecules was quantitatively examined. Real-time RT-PCR demonstrated that the expression of the cell cycle-driving molecule, cyclin-dependent kinase 4 (Cdk4), in HCC was significantly reduced by the treatments with vitamin K2, K3 and K5. Conversely, the expression of the cell cycle-suppressing molecules, Cdk inhibitor p16INK4a and retinoblastoma, in HCC was significantly enhanced by the treatments with vitamins K2, K3 and K5. These results indicate that vitamins K2, K3 and K5 exert antitumor effects on HCC by regulating the expression of G1 phase-related cell cycle molecules. These results also indicate that vitamins K2, K3 and K5 may be useful agents for the treatment of patients with HCC.

  15. 3-dimensional examination of the adult mouse subventricular zone reveals lineage-specific microdomains.

    Azim, Kasum; Fiorelli, Roberto; Zweifel, Stefan; Hurtado-Chong, Anahi; Yoshikawa, Kazuaki; Slomianka, Lutz; Raineteau, Olivier

    2012-01-01

    Recent studies suggest that the subventricular zone (SVZ) of the lateral ventricle is populated by heterogeneous populations of stem and progenitor cells that, depending on their exact location, are biased to acquire specific neuronal fates. This newly described heterogeneity of SVZ stem and progenitor cells underlines the necessity to develop methods for the accurate quantification of SVZ stem and progenitor subpopulations. In this study, we provide 3-dimensional topographical maps of slow cycling "stem" cells and progenitors based on their unique cell cycle properties. These maps revealed that both cell populations are present throughout the lateral ventricle wall as well as in discrete regions of the dorsal wall. Immunodetection of transcription factors expressed in defined progenitor populations further reveals that divergent lineages have clear regional enrichments in the rostro-caudal as well as in the dorso-ventral span of the lateral ventricle. Thus, progenitors expressing Tbr2 and Dlx2 were confined to dorsal and dorso-lateral regions of the lateral ventricle, respectively, while Mash1+ progenitors were more homogeneously distributed. All cell populations were enriched in the rostral-most region of the lateral ventricle. This diversity and uneven distribution greatly impede the accurate quantification of SVZ progenitor populations. This is illustrated by measuring the coefficient of error of estimates obtained by using increasing section sampling interval. Based on our empirical data, we provide such estimates for all progenitor populations investigated in this study. These can be used in future studies as guidelines to judge if the precision obtained with a sampling scheme is sufficient to detect statistically significant differences between experimental groups if a biological effect is present. Altogether, our study underlines the need to consider the SVZ of the lateral ventricle as a complex 3D structure and define methods to accurately assess neural

  16. 3-dimensional examination of the adult mouse subventricular zone reveals lineage-specific microdomains.

    Kasum Azim

    Full Text Available Recent studies suggest that the subventricular zone (SVZ of the lateral ventricle is populated by heterogeneous populations of stem and progenitor cells that, depending on their exact location, are biased to acquire specific neuronal fates. This newly described heterogeneity of SVZ stem and progenitor cells underlines the necessity to develop methods for the accurate quantification of SVZ stem and progenitor subpopulations. In this study, we provide 3-dimensional topographical maps of slow cycling "stem" cells and progenitors based on their unique cell cycle properties. These maps revealed that both cell populations are present throughout the lateral ventricle wall as well as in discrete regions of the dorsal wall. Immunodetection of transcription factors expressed in defined progenitor populations further reveals that divergent lineages have clear regional enrichments in the rostro-caudal as well as in the dorso-ventral span of the lateral ventricle. Thus, progenitors expressing Tbr2 and Dlx2 were confined to dorsal and dorso-lateral regions of the lateral ventricle, respectively, while Mash1+ progenitors were more homogeneously distributed. All cell populations were enriched in the rostral-most region of the lateral ventricle. This diversity and uneven distribution greatly impede the accurate quantification of SVZ progenitor populations. This is illustrated by measuring the coefficient of error of estimates obtained by using increasing section sampling interval. Based on our empirical data, we provide such estimates for all progenitor populations investigated in this study. These can be used in future studies as guidelines to judge if the precision obtained with a sampling scheme is sufficient to detect statistically significant differences between experimental groups if a biological effect is present. Altogether, our study underlines the need to consider the SVZ of the lateral ventricle as a complex 3D structure and define methods to

  17. Virtual 3-dimensional preoperative planning with the dextroscope for excision of a 4th ventricular ependymoma.

    Anil, S M; Kato, Y; Hayakawa, M; Yoshida, K; Nagahisha, S; Kanno, T

    2007-04-01

    Advances in computer imaging and technology have facilitated enhancement in surgical planning with a 3-dimensional model of the surgical plan of action utilizing advanced visualization tools in order to plan individual interactive operations with the aid of the dextroscope. This provides a proper 3-dimensional imaging insight to the pathological anatomy and sets a new dimension in collaboration for training and education. The case of a seventeen-year-old female, being operated with the aid of a preoperative 3-dimensional virtual reality planning and the practical application of the neurosurgical operation, is presented. This young lady presented with a two-year history of recurrent episodes of severe, global, throbbing headache with episodes of projectile vomiting associated with shoulder pain which progressively worsened. She had no obvious neurological deficits on clinical examination. CT and MRI showed a contrast-enhancing midline posterior fossa space-occupying lesion. Utilizing virtual imaging technology with the aid of a dextroscope which generates stereoscopic images, a 3-dimensional image was produced with the CT and MRI images. A preoperative planning for excision of the lesion was made and a real-time 3-dimensional volume was produced and surgical planning with the dextroscope was made and the lesion excised. Virtual reality has brought new proportions in 3-dimensional planning and management of various complex neuroanatomical problems that are faced during various operations. Integration of 3-dimensional imaging with stereoscopic vision makes understanding the complex anatomy easier and helps improve decision making in patient management.

  18. SOME PROBLEMS ON JUMP CONDITIONS OF SHOCK WAVES IN 3-DIMENSIONAL SOLIDS

    LI Yong-chi; YAO Lei; HU Xiu-zhang; CAO Jie-dong; DONG Jie

    2006-01-01

    Based on the general conservation laws in continuum mechanics, the Eulerian and Lagrangian descriptions of the jump conditions of shock waves in 3-dimensional solids were presented respectively. The implication of the jump conditions and their relations between each other, particularly the relation between the mass conservation and the displacement continuity, were discussed. Meanwhile the shock wave response curves in 3-dimensional solids, i.e. the Hugoniot curves were analysed, which provide the foundation for studying the coupling effects of shock waves in 3-dimensional solids.

  19. Clinical applications of 3-dimensional printing in radiation therapy

    Zhao, Yizhou, E-mail: yizhou.zhao@dal.ca [Department of Radiation Oncology, Dalhousie University, Queen Elizabeth II Health Sciences Centre, 5820 University Avenue, Halifax, Nova Scotia B3H 2Y9 (Canada); Moran, Kathryn [Department of Radiation Oncology, Dalhousie University, Queen Elizabeth II Health Sciences Centre, 5820 University Avenue, Halifax, Nova Scotia B3H 2Y9 (Canada); Yewondwossen, Mammo; Allan, James; Clarke, Scott [Department of Medical Physics, Dalhousie University, Queen Elizabeth II Health Sciences Centre, 5820 University Avenue, Halifax, Nova Scotia B3H 2Y9 (Canada); Rajaraman, Murali; Wilke, Derek; Joseph, Paul [Department of Radiation Oncology, Dalhousie University, Queen Elizabeth II Health Sciences Centre, 5820 University Avenue, Halifax, Nova Scotia B3H 2Y9 (Canada); Robar, James L. [Department of Medical Physics, Dalhousie University, Queen Elizabeth II Health Sciences Centre, 5820 University Avenue, Halifax, Nova Scotia B3H 2Y9 (Canada)

    2017-07-01

    Three-dimensional (3D) printing is suitable for the fabrication of complex radiotherapy bolus. Although investigated from dosimetric and feasibility standpoints, there are few reports to date of its use for actual patient treatment. This study illustrates the versatile applications of 3D printing in clinical radiation oncology through a selection of patient cases, namely, to create bolus for photon and modulated electron radiotherapy (MERT), as well as applicators for surface high-dose rate (HDR) brachytherapy. Photon boluses were 3D-printed to treat a recurrent squamous cell carcinoma (SCC) of the nasal septum and a basal cell carcinoma (BCC) of the posterior pinna. For a patient with a mycosis fungoides involving the upper face, a 3D-printed MERT bolus was used. To treat an SCC of the nose, a 3D-printed applicator for surface brachytherapy was made. The structures' fit to the anatomy and the radiotherapy treatment plans were assessed. Based on the treatment planning computed tomography (CT), the size of the largest air gap at the interface of the 3D-printed structure was 3 mm for the SCC of the nasal septum, 3 mm for the BCC of the pinna, 2 mm for the mycosis fungoides of the face, and 2 mm for the SCC of the nose. Acceptable treatment plans were obtained for the SCC of the nasal septum (95% isodose to 99.8% of planning target volume [PTV]), the BCC of the pinna (95% isodose to 97.7% of PTV), and the mycosis fungoides of the face (90% isodose to 92.5% of PTV). For the latter, compared with a plan with a uniform thickness bolus, the one featuring the MERT bolus achieved relative sparing of all the organs at risk (OARs) distal to the target volume, while maintaining similar target volume coverage. The surface brachytherapy plan for the SCC of the nose had adequate coverage (95% isodose to 95.6% of clinical target volume [CTV]), but a relatively high dose to the left eye, owing to its proximity to the tumor. 3D printing can be implemented effectively in

  20. Clinical applications of 3-dimensional printing in radiation therapy

    Zhao, Yizhou; Moran, Kathryn; Yewondwossen, Mammo; Allan, James; Clarke, Scott; Rajaraman, Murali; Wilke, Derek; Joseph, Paul; Robar, James L.

    2017-01-01

    Three-dimensional (3D) printing is suitable for the fabrication of complex radiotherapy bolus. Although investigated from dosimetric and feasibility standpoints, there are few reports to date of its use for actual patient treatment. This study illustrates the versatile applications of 3D printing in clinical radiation oncology through a selection of patient cases, namely, to create bolus for photon and modulated electron radiotherapy (MERT), as well as applicators for surface high-dose rate (HDR) brachytherapy. Photon boluses were 3D-printed to treat a recurrent squamous cell carcinoma (SCC) of the nasal septum and a basal cell carcinoma (BCC) of the posterior pinna. For a patient with a mycosis fungoides involving the upper face, a 3D-printed MERT bolus was used. To treat an SCC of the nose, a 3D-printed applicator for surface brachytherapy was made. The structures' fit to the anatomy and the radiotherapy treatment plans were assessed. Based on the treatment planning computed tomography (CT), the size of the largest air gap at the interface of the 3D-printed structure was 3 mm for the SCC of the nasal septum, 3 mm for the BCC of the pinna, 2 mm for the mycosis fungoides of the face, and 2 mm for the SCC of the nose. Acceptable treatment plans were obtained for the SCC of the nasal septum (95% isodose to 99.8% of planning target volume [PTV]), the BCC of the pinna (95% isodose to 97.7% of PTV), and the mycosis fungoides of the face (90% isodose to 92.5% of PTV). For the latter, compared with a plan with a uniform thickness bolus, the one featuring the MERT bolus achieved relative sparing of all the organs at risk (OARs) distal to the target volume, while maintaining similar target volume coverage. The surface brachytherapy plan for the SCC of the nose had adequate coverage (95% isodose to 95.6% of clinical target volume [CTV]), but a relatively high dose to the left eye, owing to its proximity to the tumor. 3D printing can be implemented effectively in

  1. A 3-Dimensional Biomimetic Platform to Interrogate the Safety of Autologous Fat Transfer in the Setting of Breast Cancer.

    Toyoda, Yoshiko; Celie, Karel-Bart; Xu, Jonathan T; Buro, Justin S; Jin, Julia; Lin, Alexandra J; Brown, Kristy A; Spector, Jason A

    2018-04-01

    Obesity is a known risk factor for the development and prognosis of breast cancer. Adipocytes have been identified as a source of exogenous lipids in other cancer types and may similarly provide energy to fuel malignant survival and growth in breast cancer. This relationship is of particular relevance to plastic surgery, because many reconstructions after oncologic mastectomy achieve optimal aesthetics and durability using adjunctive autologous fat transfer (AFT). Despite the increasing ubiquity and promise of AFT, many unanswered questions remain, including safety in the setting of breast cancer. Clinical studies to examine this question are underway, but an in vitro system is critical to elucidate the complex interplay between the cells that normally reside at the surgical recipient site. To study these interactions and characterize possible lipid transfer between adipocytes to breast cancer cells, we designed a 3-dimensional in vitro model using primary patient-derived tissues. Breast adipose tissue was acquired from patients undergoing breast reduction surgery. The tissue was enzymatically digested and sorted to retrieve adipocytes and adipose stromal cells. Polydimethylsiloxane wells were filled with type I collagen-encapsulated adipocytes labeled with the fluorescent lipid dye boron dipyrromethene, as well as unlabeled adipose stromal cells. A monolayer of red fluorescently labeled MDA-MB-231 and MDA-MB-468 breast cancer cells was seeded on the surface of the construct. Lipid transfer at the interface between adipocytes and breast cancer cells was analyzed. Confocal microscopy revealed a dense culture of native adipocytes containing fluorescent lipid droplets in the 3-dimensional collagen culture platform. RFP-positive breast cancer cells were found in close proximity to lipid-laden adipocytes. Lipid transfer from adipocytes to breast cancer cells was observed by the presence of boron dipyrromethene-positive lipid droplets within RFP-labeled breast cancer

  2. Monolithically integrated Helmholtz coils by 3-dimensional printing

    Li, Longguang [Department of Electrical Engineering, University of Michigan–Shanghai Jiao Tong University Joint Institute, Shanghai Jiao Tong University, Shanghai 200240 (China); Abedini-Nassab, Roozbeh; Yellen, Benjamin B., E-mail: yellen@duke.edu [Department of Electrical Engineering, University of Michigan–Shanghai Jiao Tong University Joint Institute, Shanghai Jiao Tong University, Shanghai 200240 (China); Department of Mechanical Engineering and Materials Science, Duke University, P.O. Box 90300, Hudson Hall, Durham, North Carolina 27708 (United States)

    2014-06-23

    3D printing technology is of great interest for the monolithic fabrication of integrated systems; however, it is a challenge to introduce metallic components into 3D printed molds to enable broader device functionality. Here, we develop a technique for constructing a multi-axial Helmholtz coil by injecting a eutectic liquid metal Gallium Indium alloy (EGaIn) into helically shaped orthogonal cavities constructed in a 3D printed block. The tri-axial solenoids each carry up to 3.6 A of electrical current and produce magnetic field up to 70 G. Within the central section of the coil, the field variation is less than 1% and is in agreement with theory. The flow rates and critical pressures required to fill the 3D cavities with liquid metal also agree with theoretical predictions and provide scaling trends for filling the 3D printed parts. These monolithically integrated solenoids may find future applications in electronic cell culture platforms, atomic traps, and miniaturized chemical analysis systems based on nuclear magnetic resonance.

  3. Monolithically integrated Helmholtz coils by 3-dimensional printing

    Li, Longguang; Abedini-Nassab, Roozbeh; Yellen, Benjamin B.

    2014-01-01

    3D printing technology is of great interest for the monolithic fabrication of integrated systems; however, it is a challenge to introduce metallic components into 3D printed molds to enable broader device functionality. Here, we develop a technique for constructing a multi-axial Helmholtz coil by injecting a eutectic liquid metal Gallium Indium alloy (EGaIn) into helically shaped orthogonal cavities constructed in a 3D printed block. The tri-axial solenoids each carry up to 3.6 A of electrical current and produce magnetic field up to 70 G. Within the central section of the coil, the field variation is less than 1% and is in agreement with theory. The flow rates and critical pressures required to fill the 3D cavities with liquid metal also agree with theoretical predictions and provide scaling trends for filling the 3D printed parts. These monolithically integrated solenoids may find future applications in electronic cell culture platforms, atomic traps, and miniaturized chemical analysis systems based on nuclear magnetic resonance.

  4. The application of a 3 dimensional image scanner to the strain measurement

    Mazda, Taiji; Ogawa, Hiroshi; Suzuki, Michiaki; Nakano, Yasuo.

    1993-01-01

    A large strain measuring method for a laminated seismic isolation rubber, which will be introduced to reactor buildings of the Demonstration Fast Breeder Reactor (DFBR), was developed. With using strain gages, it is difficult to measure the large strain under the large displacement condition. With using the optical instruments, it is also impossible to measure the strain of a 3 dimensional object. We developed a new measuring method in which strain is calculated from a 3 dimensional deformation with using a 3 dimensional image scanner. This method is noncontact measuring method, and it can measure the strain of a 3 dimensional object under the large deformation. This work is one part of 'The Development of FBR Seismic Isolation system' operated by Central Research Institute of Electric Power Industry. (author)

  5. Various approaches to the modelling of large scale 3-dimensional circulation in the Ocean

    Shaji, C.; Bahulayan, N.; Rao, A.D.; Dube, S.K.

    In this paper, the three different approaches to the modelling of large scale 3-dimensional flow in the ocean such as the diagnostic, semi-diagnostic (adaptation) and the prognostic are discussed in detail. Three-dimensional solutions are obtained...

  6. Bioactive glass-poly (ε-caprolactone) composite scaffolds with 3 dimensionally hierarchical pore networks

    Yun, Hui-suk; Kim, Seung-eon; Park, Eui Kyun

    2011-01-01

    Hierarchically mesoporous-macroporous-giant-porous bioactive glass/poly ε-caprolactone (PCL) composite scaffolds were prepared using a combination of the sol-gel method, evaporation-induced self-assembly process in the presence of nonionic triblock copolymer, EO 100 PO 65 EO 100 (F127), as template, salt leaching method, and rapid prototyping techniques. F127 acts as a template, inducing the formation of mesopores, NaCl with sizes between 25 and 33 μm provides macro-pores after leaching, and rapid prototyping produces giant-pores. The structure and morphology of the scaffolds were characterized by the field emission scanning electron microscopy, transmission electron microscopy, and Hg porosimetry. The mechanical properties of the scaffolds were examined by the dynamic mechanical analysis. Their in vitro bioactivities were confirmed by immersing the scaffolds in simulated body fluid. Their biocompatibilities were also evaluated by culturing human bone marrow stromal cells on the scaffolds. The scaffolds show good molding capabilities, mechanical properties, 3 dimensionally well-interconnected pore structures, bioactivities, and biocompatibilities in vitro. Depending on the amount of NaCl, the scaffolds also show unique sponge-like properties, but still retain better mechanical properties than general salt leaching derived PCL scaffolds. All of the data provide good evidence that the obtained scaffolds possess excellent potential for applications in the fields of tissue engineering and drug storage.

  7. FTY720 and two novel butterfly derivatives exert a general anti-inflammatory potential by reducing immune cell adhesion to endothelial cells through activation of S1P(3) and phosphoinositide 3-kinase.

    Imeri, Faik; Blanchard, Olivier; Jenni, Aurelio; Schwalm, Stephanie; Wünsche, Christin; Zivkovic, Aleksandra; Stark, Holger; Pfeilschifter, Josef; Huwiler, Andrea

    2015-12-01

    Sphingosine-1-phosphate (S1P) is a key lipid regulator of a variety of cellular responses including cell proliferation and survival, cell migration, and inflammatory reactions. Here, we investigated the effect of S1P receptor activation on immune cell adhesion to endothelial cells under inflammatory conditions. We show that S1P reduces both tumor necrosis factor (TNF)-α- and lipopolysaccharide (LPS)-stimulated adhesion of Jurkat and U937 cells to an endothelial monolayer. The reducing effect of S1P was reversed by the S1P1+3 antagonist VPC23019 but not by the S1P1 antagonist W146. Additionally, knockdown of S1P3, but not S1P1, by short hairpin RNA (shRNA) abolished the reducing effect of S1P, suggesting the involvement of S1P3. A suppression of immune cell adhesion was also seen with the immunomodulatory drug FTY720 and two novel butterfly derivatives ST-968 and ST-1071. On the molecular level, S1P and all FTY720 derivatives reduced the mRNA expression of LPS- and TNF-α-induced adhesion molecules including ICAM-1, VCAM-1, E-selectin, and CD44 which was reversed by the PI3K inhibitor LY294002, but not by the MEK inhibitor U0126.In summary, our data demonstrate a novel molecular mechanism by which S1P, FTY720, and two novel butterfly derivatives acted anti-inflammatory that is by suppressing gene transcription of various endothelial adhesion molecules and thereby preventing adhesion of immune cells to endothelial cells and subsequent extravasation.

  8. Axes of resistance for tooth movement: does the center of resistance exist in 3-dimensional space?

    Viecilli, Rodrigo F; Budiman, Amanda; Burstone, Charles J

    2013-02-01

    The center of resistance is considered the most important reference point for tooth movement. It is often stated that forces through this point will result in tooth translation. The purpose of this article is to report the results of numeric experiments testing the hypothesis that centers of resistance do not exist in space as 3-dimensional points, primarily because of the geometric asymmetry of the periodontal ligament. As an alternative theory, we propose that, for an arbitrary tooth, translation references can be determined by 2-dimensional projection intersections of 3-dimensional axes of resistance. Finite element analyses were conducted on a maxillary first molar model to determine the position of the axes of rotation generated by 3-dimensional couples. Translation tests were performed to compare tooth movement by using different combinations of axes of resistance as references. The couple-generated axes of rotation did not intersect in 3 dimensions; therefore, they do not determine a 3-dimensional center of resistance. Translation was obtained by using projection intersections of the 2 axes of resistance perpendicular to the force direction. Three-dimensional axes of resistance, or their 2-dimensional projection intersections, should be used to plan movement of an arbitrary tooth. Clinical approximations to a small 3-dimensional "center of resistance volume" might be adequate in nearly symmetric periodontal ligament cases. Copyright © 2013 American Association of Orthodontists. Published by Mosby, Inc. All rights reserved.

  9. Pulmonary antioxidants exert differential protective effects against ...

    Unknown

    PM collections from both urban and industrial sites caused 50% oxidative degradation of DNA in vitro at concentrations as low ... chemical analysis in order that progress can be made in ... One popular hypothesis is that PM exerts toxic effects.

  10. Exertional Heat Illness and Human Gene Expression

    Sonna, L.A; Sawka, M. N; Lilly, C. M

    2007-01-01

    Microarray analysis of gene expression at the level of RNA has generated new insights into the relationship between cellular responses to acute heat shock in vitro, exercise, and exertional heat illness...

  11. Sevoflurane improves gaseous exchange and exerts protective ...

    mice, and exerted protective effects against acute LPS-induced lung injury. ... This is an Open Access article that uses a funding model which does not charge readers .... field microscope [20]. ... by Tukey's test were used for statistical analysis.

  12. A Fortran program (RELAX3D) to solve the 3 dimensional Poisson (Laplace) equation

    Houtman, H.; Kost, C.J.

    1983-09-01

    RELAX3D is an efficient, user friendly, interactive FORTRAN program which solves the Poisson (Laplace) equation Λ 2 =p for a general 3 dimensional geometry consisting of Dirichlet and Neumann boundaries approximated to lie on a regular 3 dimensional mesh. The finite difference equations at these nodes are solved using a successive point-iterative over-relaxation method. A menu of commands, supplemented by HELP facility, controls the dynamic loading of the subroutine describing the problem case, the iterations to converge to a solution, and the contour plotting of any desired slices, etc

  13. 3-Dimensional Methodology for the Control Rod Ejection Accident Analysis Using UNICORN{sup TM}

    Jang, Chan-su; Um, Kil-sup; Ahn, Dawk-hwan [Korea Nuclear Fuel Company, Taejon (Korea, Republic of); Kim, Yo-han; Sung, Chang-kyung [KEPRI, Taejon (Korea, Republic of); Song, Jae-seung [Korea Atomic Energy Research Institute, Taejon (Korea, Republic of)

    2006-07-01

    The control rod ejection accident has been analyzed with STRIKIN-II code using the point kinetics model coupled with conservative factors to address the three dimensional aspects. This may result in a severe transient with very high fuel enthalpy deposition. KNFC, under the support of KEPRI and KAERI, is developing 3-dimensional methodology for the rod ejection accident analysis using UNICORNTM (Unified Code of RETRAN, TORC and MASTER). For this purpose, 3-dimensional MASTER-TORC codes, which have been combined with the dynamic-link library by KAERI, are used in the transient analysis of the core and RETRAN code is used to estimate the enthalpy deposition in the hot rod.

  14. 3-Dimensional Methodology for the Control Rod Ejection Accident Analysis Using UNICORNTM

    Jang, Chan-su; Um, Kil-sup; Ahn, Dawk-hwan; Kim, Yo-han; Sung, Chang-kyung; Song, Jae-seung

    2006-01-01

    The control rod ejection accident has been analyzed with STRIKIN-II code using the point kinetics model coupled with conservative factors to address the three dimensional aspects. This may result in a severe transient with very high fuel enthalpy deposition. KNFC, under the support of KEPRI and KAERI, is developing 3-dimensional methodology for the rod ejection accident analysis using UNICORNTM (Unified Code of RETRAN, TORC and MASTER). For this purpose, 3-dimensional MASTER-TORC codes, which have been combined with the dynamic-link library by KAERI, are used in the transient analysis of the core and RETRAN code is used to estimate the enthalpy deposition in the hot rod

  15. Design Strategies for Balancing Exertion Games

    Jensen, Mads Møller; Grønbæk, Kaj

    2016-01-01

    In sports, if players' physical and technical abilities are mismatched, the competition is often uninteresting for them. With the emergence of exertion games, this could be changing. Player balancing, known from video games, allows players with different skill levels to compete, however, it is un......In sports, if players' physical and technical abilities are mismatched, the competition is often uninteresting for them. With the emergence of exertion games, this could be changing. Player balancing, known from video games, allows players with different skill levels to compete, however......, it is unclear how balancing mechanisms should be applied in exertion games, where physical and digital elements are fused. In this paper, we present an exertion game and three approaches for balancing it; a physical, an explicit-digital and an implicit-digital balancing approach. A user study that compares...... these three approaches is used to investigate the qualities and challenges within each approach and explore how the player experience is affected by them. Based on these findings, we suggest four design strategies for balancing exertion games, so that players will stay engaged in the game and contain...

  16. 3-Dimensional and Interactive Istanbul University Virtual Laboratory Based on Active Learning Methods

    Ince, Elif; Kirbaslar, Fatma Gulay; Yolcu, Ergun; Aslan, Ayse Esra; Kayacan, Zeynep Cigdem; Alkan Olsson, Johanna; Akbasli, Ayse Ceylan; Aytekin, Mesut; Bauer, Thomas; Charalambis, Dimitris; Gunes, Zeliha Ozsoy; Kandemir, Ceyhan; Sari, Umit; Turkoglu, Suleyman; Yaman, Yavuz; Yolcu, Ozgu

    2014-01-01

    The purpose of this study is to develop a 3-dimensional interactive multi-user and multi-admin IUVIRLAB featuring active learning methods and techniques for university students and to introduce the Virtual Laboratory of Istanbul University and to show effects of IUVIRLAB on students' attitudes on communication skills and IUVIRLAB. Although there…

  17. Real-time 3-dimensional contrast-enhanced ultrasound in detecting hemorrhage of blunt renal trauma.

    Xu, Rui-Xue; Li, Ye-Kuo; Li, Ting; Wang, Sha-Sha; Yuan, Gui-Zhong; Zhou, Qun-Fang; Zheng, Hai-Rong; Yan, Fei

    2013-10-01

    The objective of this study is to evaluate the diagnostic value of real-time 3-dimensional contrast-enhanced ultrasound in the hemorrhage of blunt renal trauma. Eighteen healthy New Zealand white rabbits were randomly divided into 3 groups. Blunt renal trauma was performed on each group by using minitype striker. Ultrasonography, color Doppler flow imaging, and contrast-enhanced 2-dimensional and real-time 3-dimensional ultrasound were applied before and after the strike. The time to shock and blood pressure were subjected to statistical analysis. Then, a comparative study of ultrasound and pathology was carried out. All the struck kidneys were traumatic. In the ultrasonography, free fluid was found under the renal capsule. In the color Doppler flow imaging, active hemorrhage was not identified. In 2-dimensional contrast-enhanced ultrasound, active hemorrhage of the damaged kidney was characterized. Real-time 3-dimensional contrast-enhanced ultrasound showed a real-time and stereoscopic ongoing bleeding of the injured kidney. The wider the hemorrhage area in 4-dimensional contrast-enhanced ultrasound was, the faster the blood pressure decreased. Real-time 3-dimensional contrast-enhanced ultrasound is a promising noninvasive tool for stereoscopically and vividly detecting ongoing hemorrhage of blunt renal trauma in real time. © 2013.

  18. 3-dimensional orthodontics visualization system with dental study models and orthopantomograms

    Zhang, Hua; Ong, S. H.; Foong, K. W. C.; Dhar, T.

    2005-04-01

    The aim of this study is to develop a system that provides 3-dimensional visualization of orthodontic treatments. Dental plaster models and corresponding orthopantomogram (dental panoramic tomogram) are first digitized and fed into the system. A semi-auto segmentation technique is applied to the plaster models to detect the dental arches, tooth interstices and gum margins, which are used to extract individual crown models. 3-dimensional representation of roots, generated by deforming generic tooth models with orthopantomogram using radial basis functions, is attached to corresponding crowns to enable visualization of complete teeth. An optional algorithm to close the gaps between deformed roots and actual crowns by using multi-quadratic radial basis functions is also presented, which is capable of generating smooth mesh representation of complete 3-dimensional teeth. User interface is carefully designed to achieve a flexible system with as much user friendliness as possible. Manual calibration and correction is possible throughout the data processing steps to compensate occasional misbehaviors of automatic procedures. By allowing the users to move and re-arrange individual teeth (with their roots) on a full dentition, this orthodontic visualization system provides an easy and accurate way of simulation and planning of orthodontic treatment. Its capability of presenting 3-dimensional root information with only study models and orthopantomogram is especially useful for patients who do not undergo CT scanning, which is not a routine procedure in most orthodontic cases.

  19. Validation of a Novel 3-Dimensional Sonographic Method for Assessing Gastric Accommodation in Healthy Adults

    Buisman, Wijnand J; van Herwaarden-Lindeboom, MYA; Mauritz, Femke A; El Ouamari, Mourad; Hausken, Trygve; Olafsdottir, Edda J; van der Zee, David C; Gilja, Odd Helge

    OBJECTIVES: A novel automated 3-dimensional (3D) sonographic method has been developed for measuring gastric volumes. This study aimed to validate and assess the reliability of this novel 3D sonographic method compared to the reference standard in 3D gastric sonography: freehand magneto-based 3D

  20. Middle School Students' Reasoning about 3-Dimensional Objects: A Case Study

    Okumus, Samet

    2016-01-01

    According to the National Council of Teacher of Mathematics (NCTM) (2000), K-12 students should be given an opportunity to develop their spatial reasoning abilities. One of the topics that may allow students to develop their spatial skills is forming 3-dimensional objects using spinning and extrusion methods. Also, extrusion and spinning methods…

  1. On Maximal Surfaces in Certain Non-Flat 3-Dimensional Robertson-Walker Spacetimes

    Romero, Alfonso, E-mail: aromero@ugr.es [Universidad de Granada, Departamento de Geometria y Topologia (Spain); Rubio, Rafael M., E-mail: rmrubio@uco.es [Universidad de Cordoba, Departamento de Matematicas, Campus de Rabanales (Spain)

    2012-09-15

    An upper bound for the integral, on a geodesic disc, of the squared length of the gradient of a distinguished function on any maximal surface in certain non-flat 3-dimensional Robertson-Walker spacetimes is obtained. As an application, a new proof of a known Calabi-Bernstein's theorem is given.

  2. Dynamics of large scale 3-dimensional circulation of the Indian Ocean

    Swapna, P.

    -diagnostic and prognostic modes. Such a model could identify both the local and remote forcing of the Indian Ocean circulation. The other objectives of the thesis are the following: (i) To study the steady state 3-dimensional circulation of Indian Ocean based on semi...

  3. The Wilson loop expectation values in 2-and 3-dimensional SU(2) LGT

    Li Zhibing; Zheng Weihong; Guo Shuohong

    1989-01-01

    An improved Monte Carlo scheme is applied to the computation of expectation values of nxm Wilson loops in both 2-and 3-dimensional SU(2) lattice gauge theories. The results are compared with those simulated by the discrete group Y 120 and the exact results in two dimensions

  4. Full 3-dimensional digital workflow for multicomponent dental appliances A proof of concept

    Meer, van der Joerd; Vissink, Arjan; Ren, Yijin

    Background. The authors used a 3-dimensional (3D) printer and a bending robot to produce a multicomponent dental appliance to assess whether 3D digital models of the dentition are applicable for a full digital workflow. Methods. The authors scanned a volunteer's dentition with an intraoral scanner

  5. Reconstruction of Hyaline Cartilage Deep Layer Properties in 3-Dimensional Cultures of Human Articular Chondrocytes.

    Nanduri, Vibudha; Tattikota, Surendra Mohan; T, Avinash Raj; Sriramagiri, Vijaya Rama Rao; Kantipudi, Suma; Pande, Gopal

    2014-06-01

    Articular cartilage (AC) injuries and malformations are commonly noticed because of trauma or age-related degeneration. Many methods have been adopted for replacing or repairing the damaged tissue. Currently available AC repair methods, in several cases, fail to yield good-quality long-lasting results, perhaps because the reconstructed tissue lacks the cellular and matrix properties seen in hyaline cartilage (HC). To reconstruct HC tissue from 2-dimensional (2D) and 3-dimensional (3D) cultures of AC-derived human chondrocytes that would specifically exhibit the cellular and biochemical properties of the deep layer of HC. Descriptive laboratory study. Two-dimensional cultures of human AC-derived chondrocytes were established in classical medium (CM) and newly defined medium (NDM) and maintained for a period of 6 weeks. These cells were suspended in 2 mm-thick collagen I gels, placed in 24-well culture inserts, and further cultured up to 30 days. Properties of chondrocytes, grown in 2D cultures and the reconstructed 3D cartilage tissue, were studied by optical and scanning electron microscopic techniques, immunohistochemistry, and cartilage-specific gene expression profiling by reverse transcription polymerase chain reaction and were compared with those of the deep layer of native human AC. Two-dimensional chondrocyte cultures grown in NDM, in comparison with those grown in CM, showed more chondrocyte-specific gene activity and matrix properties. The NDM-grown chondrocytes in 3D cultures also showed better reproduction of deep layer properties of HC, as confirmed by microscopic and gene expression analysis. The method used in this study can yield cartilage tissue up to approximately 1.6 cm in diameter and 2 mm in thickness that satisfies the very low cell density and matrix composition properties present in the deep layer of normal HC. This study presents a novel and reproducible method for long-term culture of AC-derived chondrocytes and reconstruction of cartilage

  6. Human breast cancer histoid: an in vitro 3-dimensional co-culture model that mimics breast cancer tissue.

    Kaur, Pavinder; Ward, Brenda; Saha, Baisakhi; Young, Lillian; Groshen, Susan; Techy, Geza; Lu, Yani; Atkinson, Roscoe; Taylor, Clive R; Ingram, Marylou; Imam, S Ashraf

    2011-12-01

    Progress in our understanding of heterotypic cellular interaction in the tumor microenvironment, which is recognized to play major roles in cancer progression, has been hampered due to unavailability of an appropriate in vitro co-culture model. The aim of this study was to generate an in vitro 3-dimensional human breast cancer model, which consists of cancer cells and fibroblasts. Breast cancer cells (UACC-893) and fibroblasts at various densities were co-cultured in a rotating suspension culture system to establish co-culture parameters. Subsequently, UACC-893, BT.20, or MDA.MB.453 were co-cultured with fibroblasts for 9 days. Co-cultures resulted in the generation of breast cancer histoid (BCH) with cancer cells showing the invasion of fibroblast spheroids, which were visualized by immunohistochemical (IHC) staining of sections (4 µm thick) of BCH. A reproducible quantitative expression of C-erbB.2 was detected in UACC-893 cancer cells in BCH sections by IHC staining and the Automated Cellular Imaging System. BCH sections also consistently exhibited qualitative expression of pancytokeratins, p53, Ki-67, or E-cadherin in cancer cells and that of vimentin or GSTPi in fibroblasts, fibronectin in the basement membrane and collagen IV in the extracellular matrix. The expression of the protein analytes and cellular architecture of BCH were markedly similar to those of breast cancer tissue.

  7. Does heavy physical exertion trigger myocardial infarction?

    Hallqvist, J; Möller, J; Ahlbom, A

    2000-01-01

    To study possible triggering of first events of acute myocardial infarction by heavy physical exertion, the authors conducted a case-crossover analysis (1993-1994) within a population-based case-referent study in Stockholm County, Sweden (the Stockholm Heart Epidemiology Program). Interviews were...

  8. Pulmonary Toxicity in Stage III Non-Small Cell Lung Cancer Patients Treated With High-Dose (74 Gy) 3-Dimensional Conformal Thoracic Radiotherapy and Concurrent Chemotherapy Following Induction Chemotherapy: A Secondary Analysis of Cancer and Leukemia Group B (CALGB) Trial 30105

    Salama, Joseph K.; Stinchcombe, Thomas E.; Gu Lin; Wang Xiaofei; Morano, Karen; Bogart, Jeffrey A.; Crawford, Jeffrey C.; Socinski, Mark A.; Blackstock, A. William; Vokes, Everett E.

    2011-01-01

    Purpose: Cancer and Leukemia Group B (CALGB) 30105 tested two different concurrent chemoradiotherapy platforms with high-dose (74 Gy) three-dimensional conformal radiotherapy (3D-CRT) after two cycles of induction chemotherapy for Stage IIIA/IIIB non–small cell lung cancer (NSCLC) patients to determine if either could achieve a primary endpoint of >18-month median survival. Final results of 30105 demonstrated that induction carboplatin and gemcitabine and concurrent gemcitabine 3D-CRT was not feasible because of treatment-related toxicity. However, induction and concurrent carboplatin/paclitaxel with 74 Gy 3D-CRT had a median survival of 24 months, and is the basis for the experimental arm in CALGB 30610/RTOG 0617/N0628. We conducted a secondary analysis of all patients to determine predictors of treatment-related pulmonary toxicity. Methods and Materials: Patient, tumor, and treatment-related variables were analyzed to determine their relation with treatment-related pulmonary toxicity. Results: Older age, higher N stage, larger planning target volume (PTV)1, smaller total lung volume/PTV1 ratio, larger V20, and larger mean lung dose were associated with increasing pulmonary toxicity on univariate analysis. Multivariate analysis confirmed that V20 and nodal stage as well as treatment with concurrent gemcitabine were associated with treatment-related toxicity. A high-risk group comprising patients with N3 disease and V20 >38% was associated with 80% of Grades 3-5 pulmonary toxicity cases. Conclusions: Elevated V20 and N3 disease status are important predictors of treatment related pulmonary toxicity in patients treated with high-dose 3D-CRT and concurrent chemotherapy. Further studies may use these metrics in considering patients for these treatments.

  9. Pulmonary Toxicity in Stage III Non-Small Cell Lung Cancer Patients Treated With High-Dose (74 Gy) 3-Dimensional Conformal Thoracic Radiotherapy and Concurrent Chemotherapy Following Induction Chemotherapy: A Secondary Analysis of Cancer and Leukemia Group B (CALGB) Trial 30105

    Salama, Joseph K., E-mail: joseph.salama@duke.edu [Duke University Medical Center, Durham, NC (United States); Stinchcombe, Thomas E. [University of North Carolina at Chapel Hill, Chapel Hill, NC (United States); Gu Lin; Wang Xiaofei [CALGB Statistical Center, Duke University Medical Center, Durham, NC (United States); Morano, Karen [Quality Assurance Review Center, Lincoln, RI (United States); Bogart, Jeffrey A. [State University of New York Upstate Medical University, Syracuse, NY (United States); Crawford, Jeffrey C. [Duke University Medical Center, Durham, NC (United States); Socinski, Mark A. [University of North Carolina at Chapel Hill, Chapel Hill, NC (United States); Blackstock, A. William [Wake Forest University School of Medicine, Winston-Salem, NC (United States); Vokes, Everett E. [University of Chicago, Chicago, IL (United States)

    2011-11-15

    Purpose: Cancer and Leukemia Group B (CALGB) 30105 tested two different concurrent chemoradiotherapy platforms with high-dose (74 Gy) three-dimensional conformal radiotherapy (3D-CRT) after two cycles of induction chemotherapy for Stage IIIA/IIIB non-small cell lung cancer (NSCLC) patients to determine if either could achieve a primary endpoint of >18-month median survival. Final results of 30105 demonstrated that induction carboplatin and gemcitabine and concurrent gemcitabine 3D-CRT was not feasible because of treatment-related toxicity. However, induction and concurrent carboplatin/paclitaxel with 74 Gy 3D-CRT had a median survival of 24 months, and is the basis for the experimental arm in CALGB 30610/RTOG 0617/N0628. We conducted a secondary analysis of all patients to determine predictors of treatment-related pulmonary toxicity. Methods and Materials: Patient, tumor, and treatment-related variables were analyzed to determine their relation with treatment-related pulmonary toxicity. Results: Older age, higher N stage, larger planning target volume (PTV)1, smaller total lung volume/PTV1 ratio, larger V20, and larger mean lung dose were associated with increasing pulmonary toxicity on univariate analysis. Multivariate analysis confirmed that V20 and nodal stage as well as treatment with concurrent gemcitabine were associated with treatment-related toxicity. A high-risk group comprising patients with N3 disease and V20 >38% was associated with 80% of Grades 3-5 pulmonary toxicity cases. Conclusions: Elevated V20 and N3 disease status are important predictors of treatment related pulmonary toxicity in patients treated with high-dose 3D-CRT and concurrent chemotherapy. Further studies may use these metrics in considering patients for these treatments.

  10. A Quantitative Assessment of Lip Movements in Different Facial Expressions Through 3-Dimensional on 3-Dimensional Superimposition: A Cross-Sectional Study.

    Gibelli, Daniele; Codari, Marina; Pucciarelli, Valentina; Dolci, Claudia; Sforza, Chiarella

    2017-11-23

    The quantitative assessment of facial modifications from mimicry is of relevant interest for the rehabilitation of patients who can no longer produce facial expressions. This study investigated a novel application of 3-dimensional on 3-dimensional superimposition for facial mimicry. This cross-sectional study was based on 10 men 30 to 40 years old who underwent stereophotogrammetry for neutral, happy, sad, and angry expressions. Registration of facial expressions on the neutral expression was performed. Root mean square (RMS) point-to-point distance in the labial area was calculated between each facial expression and the neutral one and was considered the main parameter for assessing facial modifications. In addition, effect size (Cohen d) was calculated to assess the effects of labial movements in relation to facial modifications. All participants were free from possible facial deformities, pathologies, or trauma that could affect facial mimicry. RMS values of facial areas differed significantly among facial expressions (P = .0004 by Friedman test). The widest modifications of the lips were observed in happy expressions (RMS, 4.06 mm; standard deviation [SD], 1.14 mm), with a statistically relevant difference compared with the sad (RMS, 1.42 mm; SD, 1.15 mm) and angry (RMS, 0.76 mm; SD, 0.45 mm) expressions. The effect size of labial versus total face movements was limited for happy and sad expressions and large for the angry expression. This study found that a happy expression provides wider modifications of the lips than the other facial expressions and suggests a novel procedure for assessing regional changes from mimicry. Copyright © 2017 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

  11. Automatic segmentation and 3-dimensional display based on the knowledge of head MRI images

    Suzuki, Hidetomo; Toriwaki, Jun-ichiro.

    1987-01-01

    In this paper we present a procedure which automatically extracts soft tissues, such as subcutaneous fat, brain, and cerebral ventricle, from the multislice MRI images of head region, and displays their 3-dimensional images. Segmentation of soft tissues is done by use of an iterative thresholding. In order to select the optimum threshold value automatically, we introduce a measure to evaluate the goodness of segmentation into this procedure. When the measure satisfies given conditions, iteration of thresholding terminates, and the final result of segmentation is extracted by using the current threshold value. Since this procedure can execute segmentation and calculation of the goodness measure in each slice automatically, it remarkably decreases efforts of users. Moreover, the 3-dimensional display of the segmented tissues shows that this procedure can extract the shape of each soft tissue with reasonable precision for clinical use. (author)

  12. Exact, rotational, infinite energy, blowup solutions to the 3-dimensional Euler equations

    Yuen, Manwai

    2011-01-01

    In this Letter, we construct a new class of blowup or global solutions with elementary functions to the 3-dimensional compressible or incompressible Euler and Navier-Stokes equations. And the corresponding blowup or global solutions for the incompressible Euler and Naiver-Stokes equations are also given. Our constructed solutions are similar to the famous Arnold-Beltrami-Childress (ABC) flow. The obtained solutions with infinite energy can exhibit the interesting behaviors locally. Furthermore, due to divu → =0 for the solutions, the solutions also work for the 3-dimensional incompressible Euler and Navier-Stokes equations. -- Highlights: → We construct a new class of solutions to the 3D compressible or incompressible Euler and Navier-Stokes equations. → The constructed solutions are similar to the famous Arnold-Beltrami-Childress flow. → The solutions with infinite energy can exhibit the interesting behaviors locally.

  13. An Individualized 3-Dimensional Designed and Printed Conformer After Dermis Fat Grafting for Complex Sockets.

    Mourits, Daphne L; Remmers, Jelmer S; Tan, Stevie H; Moll, Annette C; Hartong, Dyonne T

    2018-04-03

    To introduce a novel technique to design individually customized conformers for postenucleation sockets with dermis fat implants. We use a 3-dimensional scan of the frontal face/orbit and eyelid contour to design an individualized conformer. This polymethylmetacrylate printed conformer is adapted to patients' socket, palpebral fissures, horizontal eyelid aperture, curvature of the eyelids, and mean diameter of patients' contralateral eye. Sutures through holes in the inferior part of the conformer and in the extension can be placed to fixate the conformer and anchor fornix deepening sutures. A correct fitting conformer can be printed and attached to the socket and eyelids. The shape of this conformer can be used subsequently postsurgically to design the ocular prosthesis. Presurgical planning is important to anticipate for a functional socket to adequately fit an artificial eye. The presented technique using 3-dimensional imaging, designing, and printing promises to prevent conformer extrusion and forniceal shortening.

  14. Born-Infeld determinantal gravity and the taming of the conical singularity in 3-dimensional spacetime

    Ferraro, Rafael, E-mail: ferraro@iafe.uba.a [Instituto de Astronomia y Fisica del Espacio, Casilla de Correo 67, Sucursal 28, 1428 Buenos Aires (Argentina); Departamento de Fisica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria, Pabellon I, 1428 Buenos Aires (Argentina); Fiorini, Franco, E-mail: franco@iafe.uba.a [Instituto de Astronomia y Fisica del Espacio, Casilla de Correo 67, Sucursal 28, 1428 Buenos Aires (Argentina)

    2010-08-30

    In the context of Born-Infeld determinantal gravity formulated in an n-dimensional spacetime with absolute parallelism, we found an exact 3-dimensional vacuum circular symmetric solution without cosmological constant consisting in a rotating spacetime with non-singular behavior. The space behaves at infinity as the conical geometry typical of 3-dimensional General Relativity without cosmological constant. However, the solution has no conical singularity because the space ends at a minimal circle that no freely falling particle can ever reach in a finite proper time. The space is curved, but no divergences happen since the curvature invariants vanish at both asymptotic limits. Remarkably, this very mechanism also forbids the existence of closed timelike curves in such a spacetime.

  15. Born-Infeld determinantal gravity and the taming of the conical singularity in 3-dimensional spacetime

    Ferraro, Rafael; Fiorini, Franco

    2010-01-01

    In the context of Born-Infeld determinantal gravity formulated in an n-dimensional spacetime with absolute parallelism, we found an exact 3-dimensional vacuum circular symmetric solution without cosmological constant consisting in a rotating spacetime with non-singular behavior. The space behaves at infinity as the conical geometry typical of 3-dimensional General Relativity without cosmological constant. However, the solution has no conical singularity because the space ends at a minimal circle that no freely falling particle can ever reach in a finite proper time. The space is curved, but no divergences happen since the curvature invariants vanish at both asymptotic limits. Remarkably, this very mechanism also forbids the existence of closed timelike curves in such a spacetime.

  16. The application of 3-dimensional CAT scan reconstruction for maxillofacial deformities

    Shimbashi, Takeshi; Tomonari, Hiroshi; Ishii, Masahiro; Sakurai, Nobuaki; Kodachi, Ken; Kubo, Eiichi; Tsuchida, Yoshitaka; Takagi, Hiroshi.

    1987-01-01

    It has been found very useful to recognize craniofacial deformities 3-dimensionally, and to observe 3-D Cat scan reconstructions that have been performed by others. Thus, starting in 1985, we have developed a 3-D CT system that combines conventional X-ray CAT scan hardware to a 3-Dimensional display software. In this paper we report on our 3-CT system, its basic algorithm, and its basic processes, i.e., the threshold process, the perspective process, the shading process and the display. The mixture shading which we have developed makes 3-D displays clearer and more natural. Also, we have applied our 3-D display to 39 cases of maxillofacial diformities. (author)

  17. Spinorial characterizations of surfaces into 3-dimensional psuedo-Riemannian space forms

    Lawn , Marie-Amélie; Roth , Julien

    2011-01-01

    9 pages; We give a spinorial characterization of isometrically immersed surfaces of arbitrary signature into 3-dimensional pseudo-Riemannian space forms. For Lorentzian surfaces, this generalizes a recent work of the first author in $\\mathbb{R}^{2,1}$ to other Lorentzian space forms. We also characterize immersions of Riemannian surfaces in these spaces. From this we can deduce analogous results for timelike immersions of Lorentzian surfaces in space forms of corresponding signature, as well ...

  18. The Origin of Chern-Simons Modified Gravity from an 11 + 3-Dimensional Manifold

    J. A. Helayël-Neto

    2017-01-01

    Full Text Available It is our aim to show that the Chern-Simons terms of modified gravity can be understood as generated by the addition of a 3-dimensional algebraic manifold to an initial 11-dimensional space-time manifold; this builds up an 11+3-dimensional space-time. In this system, firstly, some fields living in the bulk join the fields that live on the 11-dimensional manifold, so that the rank of the gauge fields exceeds the dimension of the algebra; consequently, there emerges an anomaly. To solve this problem, another 11-dimensional manifold is included in the 11+3-dimensional space-time, and it interacts with the initial manifold by exchanging Chern-Simon fields. This mechanism is able to remove the anomaly. Chern-Simons terms actually produce an extra manifold in the pair of 11-dimensional manifolds of the 11+3-space-time. Summing up the topology of both the 11-dimensional manifolds and the topology of the exchanged Chern-Simons manifold in the bulk, we conclude that the total topology shrinks to one, which is in agreement with the main idea of the Big Bang theory.

  19. Candidate gene analyses of 3-dimensional dentoalveolar phenotypes in subjects with malocclusion.

    Weaver, Cole A; Miller, Steven F; da Fontoura, Clarissa S G; Wehby, George L; Amendt, Brad A; Holton, Nathan E; Allareddy, Veeratrishul; Southard, Thomas E; Moreno Uribe, Lina M

    2017-03-01

    Genetic studies of malocclusion etiology have identified 4 deleterious mutations in genes DUSP6,ARHGAP21, FGF23, and ADAMTS1 in familial Class III cases. Although these variants may have large impacts on Class III phenotypic expression, their low frequency (common genetic variations in craniofacial candidate genes and 3-dimensional dentoalveolar phenotypes in patients with malocclusion. Pretreatment dental casts or cone-beam computed tomographic images from 300 healthy subjects were digitized with 48 landmarks. The 3-dimensional coordinate data were submitted to a geometric morphometric approach along with principal component analysis to generate continuous phenotypes including symmetric and asymmetric components of dentoalveolar shape variation, fluctuating asymmetry, and size. The subjects were genotyped for 222 single-nucleotide polymorphisms in 82 genes/loci, and phenotpye-genotype associations were tested via multivariate linear regression. Principal component analysis of symmetric variation identified 4 components that explained 68% of the total variance and depicted anteroposterior, vertical, and transverse dentoalveolar discrepancies. Suggestive associations (P centroid size, a proxy for dentoalveolar size variation with 4p16.1 and SNAI1. Specific genetic pathways associated with 3-dimensional dentoalveolar phenotypic variation in malocclusions were identified. Copyright © 2016 American Association of Orthodontists. Published by Elsevier Inc. All rights reserved.

  20. The 3-dimensional play of human parechovirus infection; Cell, virus and antibody

    Westerhuis, B.M.

    2014-01-01

    HPeV3 has been shown to be the ‘odd one out’ compared to the other genotypes; HPeV3 is more often associated with severe disease, infects significantly younger infants, seems to be more difficult to culture, and does not recombine with other HPeV types. The aim of this thesis is to study whether

  1. Down-regulation of 14-3-3β exerts anti-cancer effects through inducing ER stress in human glioma U87 cells: Involvement of CHOP–Wnt pathway

    Cao, Lei; Lei, Hui; Chang, Ming-Ze; Liu, Zhi-Qin [Department of Neurological Disease, Xi' an Central Hospital, Xi' an Jiaotong University, Xi' an, Shaanxi 710000 (China); Bie, Xiao-Hua, E-mail: biexiaohua_xjtu@126.com [Department of Functional Neurosurgery, Xi' an Red Cross Hospital, Xi' an Jiaotong University, Xi' an, Shaanxi 710054 (China)

    2015-07-10

    We previously identified 14-3-3β as a tumor-specific isoform of 14-3-3 protein in astrocytoma, but its functional role in glioma cells and underlying mechanisms are poorly understood. In the present study, we investigated the effects of 14-3-3β inhibition in human glioma U87 cells using specific targeted small interfering RNA (siRNA). The results showed that 14-3-3β is highly expressed in U87 cells but not in normal astrocyte SVGp12 cells. Knockdown of 14-3-3β by Si-14-3-3β transfection significantly decreased the cell viability but increased the LDH release in a time-dependent fashion in U87 cells, and these effects were accompanied with G0/G1 cell cycle arrest and apoptosis. In addition, 14-3-3β knockdown induced ER stress in U87 cells, as evidenced by ER calcium release, increased expression of XBP1S mRNA and induction of ER related pro-apoptotic factors. Down-regulation of 14-3-3β significantly decreased the nuclear localization of β-catenin and inhibited Topflash activity, which was shown to be reversely correlated with CHOP. Furthermore, Si-CHOP and sFRP were used to inhibit CHOP and Wnt, respectively. The results showed that the anti-cancer effects of 14-3-3β knockdown in U87 cells were mediated by increased expression of CHOP and followed inhibition of Wnt/β-catenin pathway. In summary, the remarkable efficiency of 14-3-3β knockdown to induce apoptotic cell death in U87 cells may find therapeutic application for the treatment of glioma patients. - Highlights: • Knockdown of 14-3-3β leads to cytotoxicity in human glioma U87 cells. • Knockdown of 14-3-3β induces cell cycle arrest and apoptosis in U87 cells. • Knockdown of 14-3-3β results in ER stress in U87 cells. • Knockdown of 14-3-3β inhibits Wnt/β-catenin pathway via CHOP activation.

  2. Down-regulation of 14-3-3β exerts anti-cancer effects through inducing ER stress in human glioma U87 cells: Involvement of CHOP–Wnt pathway

    Cao, Lei; Lei, Hui; Chang, Ming-Ze; Liu, Zhi-Qin; Bie, Xiao-Hua

    2015-01-01

    We previously identified 14-3-3β as a tumor-specific isoform of 14-3-3 protein in astrocytoma, but its functional role in glioma cells and underlying mechanisms are poorly understood. In the present study, we investigated the effects of 14-3-3β inhibition in human glioma U87 cells using specific targeted small interfering RNA (siRNA). The results showed that 14-3-3β is highly expressed in U87 cells but not in normal astrocyte SVGp12 cells. Knockdown of 14-3-3β by Si-14-3-3β transfection significantly decreased the cell viability but increased the LDH release in a time-dependent fashion in U87 cells, and these effects were accompanied with G0/G1 cell cycle arrest and apoptosis. In addition, 14-3-3β knockdown induced ER stress in U87 cells, as evidenced by ER calcium release, increased expression of XBP1S mRNA and induction of ER related pro-apoptotic factors. Down-regulation of 14-3-3β significantly decreased the nuclear localization of β-catenin and inhibited Topflash activity, which was shown to be reversely correlated with CHOP. Furthermore, Si-CHOP and sFRP were used to inhibit CHOP and Wnt, respectively. The results showed that the anti-cancer effects of 14-3-3β knockdown in U87 cells were mediated by increased expression of CHOP and followed inhibition of Wnt/β-catenin pathway. In summary, the remarkable efficiency of 14-3-3β knockdown to induce apoptotic cell death in U87 cells may find therapeutic application for the treatment of glioma patients. - Highlights: • Knockdown of 14-3-3β leads to cytotoxicity in human glioma U87 cells. • Knockdown of 14-3-3β induces cell cycle arrest and apoptosis in U87 cells. • Knockdown of 14-3-3β results in ER stress in U87 cells. • Knockdown of 14-3-3β inhibits Wnt/β-catenin pathway via CHOP activation

  3. Functional analysis of Peutz-Jeghers mutations reveals that the LKB1 C-terminal region exerts a crucial role in regulating both the AMPK pathway and the cell polarity.

    Forcet, C.; Etienne-Manneville, S.; Gaude, H.; Fournier, L.; Debilly, S.; Salmi, M.; Baas, A.; Olschwang, S.; Clevers, J.C.; Billaud, M.

    2005-01-01

    Germline mutations of the LKB1 gene are responsible for the cancer-prone Peutz-Jeghers syndrome (PJS). LKB1 encodes a serine-threonine kinase that acts as a regulator of cell cycle, metabolism and cell polarity. The majority of PJS missense mutations abolish LKB1 enzymatic activity and thereby

  4. 3-Dimensional quantitative detection of nanoparticle content in biological tissue samples after local cancer treatment

    Rahn, Helene, E-mail: helene.rahn@gmail.com [Institute of Fluid Mechanics, Chair of Magnetofluiddynamics, Technische Universitaet Dresden, Dresden 01069 (Germany); Alexiou, Christoph [ENT-Department, Section for Experimental Oncology and Nanomedicine (Else Kröner-Fresenius-Stiftungsprofessur), University Hospital Erlangen, Waldstraße 1, Erlangen 91054 (Germany); Trahms, Lutz [Physikalisch-Technische Bundesanstalt, Abbestraße 2-12, Berlin 10587 (Germany); Odenbach, Stefan [Institute of Fluid Mechanics, Chair of Magnetofluiddynamics, Technische Universitaet Dresden, Dresden 01069 (Germany)

    2014-06-01

    X-ray computed tomography is nowadays used for a wide range of applications in medicine, science and technology. X-ray microcomputed tomography (XµCT) follows the same principles used for conventional medical CT scanners, but improves the spatial resolution to a few micrometers. We present an example of an application of X-ray microtomography, a study of 3-dimensional biodistribution, as along with the quantification of nanoparticle content in tumoral tissue after minimally invasive cancer therapy. One of these minimal invasive cancer treatments is magnetic drug targeting, where the magnetic nanoparticles are used as controllable drug carriers. The quantification is based on a calibration of the XµCT-equipment. The developed calibration procedure of the X-ray-µCT-equipment is based on a phantom system which allows the discrimination between the various gray values of the data set. These phantoms consist of a biological tissue substitute and magnetic nanoparticles. The phantoms have been studied with XµCT and have been examined magnetically. The obtained gray values and nanoparticle concentration lead to a calibration curve. This curve can be applied to tomographic data sets. Accordingly, this calibration enables a voxel-wise assignment of gray values in the digital tomographic data set to nanoparticle content. Thus, the calibration procedure enables a 3-dimensional study of nanoparticle distribution as well as concentration. - Highlights: • Local cancer treatments are promising in reducing negative side effects occurring during conventional chemotherapy. • The nanoparticles play an important role in delivering drugs to the designated area during local cancer treatments as magnetic drug targeting. • We study the nanoparticles distribution in tumor tissue after magnetic drug targeting with X-ray computed tomography. • We achieved a 3-dimensional quantification of the nanoparticles content in tumor tissue out of digital tomographic data.

  5. Development of a 3-dimensional seismic isolation floor for computer systems

    Kurihara, M.; Shigeta, M.; Nino, T.; Matsuki, T.

    1991-01-01

    In this paper, we investigated the applicability of a seismic isolation floor as a method for protecting computer systems from strong earthquakes, such as computer systems in nuclear power plants. Assuming that the computer system is guaranteed for 250 cm/s 2 of input acceleration in the horizontal and vertical directions as the seismic performance, the basic design specification of the seismic isolation floor is considered as follows. Against S 1 level earthquakes, the maximum acceleration response of the seismic isolation floor in the horizontal and vertical directions is kept less than 250 cm/s 2 to maintain continuous computer operation. Against S 2 level earthquakes, the isolation floor allows large horizontal movement and large displacement of the isolation devices to reduce the acceleration response, although it is not guaranteed to be less than 250 cm/s 2 . By reducing the acceleration response, however, serious damage to the computer systems is reduced, so that they can be restarted after an earthquake. Usually, seismic isolation floor systems permit 2-dimensional (horizontal) isolation. However, in the case of just-under-seated earthquakes, which have large vertical components, the vertical acceleration response of this system is amplified by the lateral vibration of the frame of the isolation floor. Therefore, in this study a 3-dimensional seismic isolation floor, including vertical isolation, was developed. This paper describes 1) the experimental results of the response characteristics of the 3-dimensional seismic isolation floor built as a trial using a 3-dimensional shaking table, and 2) comparison of a 2-dimensional analytical model, for motion in one horizontal direction and the vertical direction, to experimental results. (J.P.N.)

  6. Dental implant customization using numerical optimization design and 3-dimensional printing fabrication of zirconia ceramic.

    Cheng, Yung-Chang; Lin, Deng-Huei; Jiang, Cho-Pei; Lin, Yuan-Min

    2017-05-01

    This study proposes a new methodology for dental implant customization consisting of numerical geometric optimization and 3-dimensional printing fabrication of zirconia ceramic. In the numerical modeling, exogenous factors for implant shape include the thread pitch, thread depth, maximal diameter of implant neck, and body size. Endogenous factors are bone density, cortical bone thickness, and non-osseointegration. An integration procedure, including uniform design method, Kriging interpolation and genetic algorithm, is applied to optimize the geometry of dental implants. The threshold of minimal micromotion for optimization evaluation was 100 μm. The optimized model is imported to the 3-dimensional slurry printer to fabricate the zirconia green body (powder is bonded by polymer weakly) of the implant. The sintered implant is obtained using a 2-stage sintering process. Twelve models are constructed according to uniform design method and simulated the micromotion behavior using finite element modeling. The result of uniform design models yields a set of exogenous factors that can provide the minimal micromotion (30.61 μm), as a suitable model. Kriging interpolation and genetic algorithm modified the exogenous factor of the suitable model, resulting in 27.11 μm as an optimization model. Experimental results show that the 3-dimensional slurry printer successfully fabricated the green body of the optimization model, but the accuracy of sintered part still needs to be improved. In addition, the scanning electron microscopy morphology is a stabilized t-phase microstructure, and the average compressive strength of the sintered part is 632.1 MPa. Copyright © 2016 John Wiley & Sons, Ltd.

  7. Indentation in the Right Ventricle by an Incomplete Pericardium on 3-Dimensional Reconstructed Computed Tomography

    Hak Ju Kim

    2017-08-01

    Full Text Available We report the case of a 17-year-old girl who presented with an indentation in the right ventricle caused by an incomplete pericardium on preoperative 3-dimensional reconstructed computed tomography. She was to undergo surgery for a partial atrioventricular septal defect and secundum atrial septal defect. Preoperative electrocardiography revealed occasional premature ventricular beats. We found the absence of the left side of the pericardium intraoperatively, and this absence caused strangulation of the diaphragmatic surface of the right ventricle. After correcting the lesion, the patient’s rhythm disturbances improved.

  8. Fractal dimensions from a 3-dimensional intermittency analysis in e+e- annihilation

    Behrend, H.J.; Criegee, L.; Field, J.H.; Franke, G.; Jung, H.; Meyer, J.; Podobrin, O.; Schroeder, V.; Winter, G.G.; Bussey, P.J.; Campbell, A.J.; Hendry, D.; Lumsdon, S.J.; Skillicorn, I.O.; Ahme, J.; Blobel, V.; Feindt, M.; Fenner, H.; Harjes, J.; Koehne, J.H.; Peters, J.H.; Spitzer, H.; Weihrich, T.; Boer, W. de; Buschhorn, G.; Grindhammer, G.; Gunderson, B.; Kiesling, C.; Kotthaus, R.; Kroha, H.; Lueers, D.; Oberlack, H.; Schacht, P.; Scholz, S.; Wiedenmann, W.; Davier, M.; Grivaz, J.F.; Haissinski, J.; Journe, V.; Le Diberder, F.; Veillet, J.J.; Cozzika, G.; Ducros, Y.; Alexander, G.; Beck, A.; Bella, G.; Grunhaus, J.; Klatchko, A.; Levy, A.; Milstene, C.

    1990-10-01

    The intermittency structure of multihadronic e + e - annihilation is analyzed by evaluating the factorial moments F 2 -F 5 in 3-dimensional Lorentz invariant phase space as a function of the resolution scale. We interpret our data in the language of fractal objects. It turns out that the fractal dimension depends on the resolution scale in a way that can be attributed to geometrical resolution effects and dynamical effects, such as the π 0 Dalitz decay. The LUND 7.2 hadronization model provides an excellent description of the data. There is no indication of unexplained multiplicity fluctuations in small phase space regions. (orig.)

  9. 3-dimensional lattice studies of the electroweak phase transition at MHiggs∼ 70 GeV

    Guertler, M.; Perlt, H.; Schiller, A.; Ilgenfritz, E.M.; Kripfganz, J.

    1996-06-01

    We study the electroweak phase transition by lattice simulations of an effective 3-dimensional theory, for a Higgs mass of about 70 GeV. Exploiting, among others, a variant of the equal weight criterion of phase equilibrium, we obtain transition temperature, latent heat and surface tension, and compare with M H ∼35 GeV. In the broken phase masses and Higgs condensates are compared to perturbation theory. For the symmetric phase, bound state masses and the static force are determined. (orig.)

  10. Incorporating a 3-dimensional printer into the management of early-stage cervical cancer.

    Baek, Min-Hyun; Kim, Dae-Yeon; Kim, Namkug; Rhim, Chae Chun; Kim, Jong-Hyeok; Nam, Joo-Hyun

    2016-08-01

    We used a 3-dimensional (3D) printer to create anatomical replicas of real lesions and tested its application in cervical cancer. Our study patient decided to undergo radical hysterectomy after seeing her 3D model which was then used to plan and simulate this surgery. Using 3D printers to create patient-specific 3D tumor models may aid cervical cancer patients make treatment decisions. This technology will lead to better surgical and oncological outcomes for cervical cancer patients. J. Surg. Oncol. 2016;114:150-152. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  11. Spinorial Characterizations of Surfaces into 3-dimensional Pseudo-Riemannian Space Forms

    Lawn, Marie-Amélie; Roth, Julien

    2011-01-01

    We give a spinorial characterization of isometrically immersed surfaces of arbitrary signature into 3-dimensional pseudo-Riemannian space forms. This generalizes a recent work of the first author for spacelike immersed Lorentzian surfaces in ℝ 2,1 to other Lorentzian space forms. We also characterize immersions of Riemannian surfaces in these spaces. From this we can deduce analogous results for timelike immersions of Lorentzian surfaces in space forms of corresponding signature, as well as for spacelike and timelike immersions of surfaces of signature (0, 2), hence achieving a complete spinorial description for this class of pseudo-Riemannian immersions.

  12. Visualized fuelling process and 3 dimensional reactivity device and core monitor

    Patterson, B.; Cusson, R.; Crowell, T.

    2006-01-01

    A new reactor fueling animated graphical display and a 3 dimensional view of the reactor core display are presented that are useful for the physics fuelling engineer, the Control Room Operators, the fuel handling operators and the fuel handling support engineers. Data is downloaded from the online fuelling computer to a data server that is network accessible. The fuelling display and 3Dview display can run on any network connected Computer. The animated graphical fuelling display offers a huge reduction in cognitive workload for all users. The authors recommend that animated graphical displays be developed and utilized wherever personnel have to visualize complex equipment operation. (author)

  13. Distemper virus encephalitis exerts detrimental effects on hippocampal neurogenesis.

    von Rüden, E-L; Avemary, J; Zellinger, C; Algermissen, D; Bock, P; Beineke, A; Baumgärtner, W; Stein, V M; Tipold, A; Potschka, H

    2012-08-01

    Despite knowledge about the impact of brain inflammation on hippocampal neurogenesis, data on the influence of virus encephalitis on dentate granule cell neurogenesis are so far limited. Canine distemper is considered an interesting model of virus encephalitis, which can be associated with a chronic progressing disease course and can cause symptomatic seizures. To determine the impact of canine distemper virus (CDV) infection on hippocampal neurogenesis, we compared post-mortem tissue from dogs with infection with and without seizures, from epileptic dogs with non-viral aetiology and from dogs without central nervous system diseases. The majority of animals with infection and with epilepsy of non-viral aetiology exhibited neuronal progenitor numbers below the age average in controls. Virus infection with and without seizures significantly decreased the mean number of neuronal progenitor cells by 43% and 76% as compared to age-matched controls. Ki-67 labelling demonstrated that hippocampal cell proliferation was neither affected by infection nor by epilepsy of non-viral aetiology. Analysis of CDV infection in cells expressing caspase-3, doublecortin or Ki-67 indicated that infection of neuronal progenitor cells is extremely rare and suggests that infection might damage non-differentiated progenitor cells, hamper neuronal differentiation and promote glial differentiation. A high inter-individual variance in the number of lectin-reactive microglial cells was evident in dogs with distemper infection. Statistical analyses did not reveal a correlation between the number of lectin-reactive microglia cells and neuronal progenitor cells. Our data demonstrate that virus encephalitis with and without seizures can exert detrimental effects on hippocampal neurogenesis, which might contribute to long-term consequences of the disease. The lack of a significant impact of distemper virus on Ki-67-labelled cells indicates that the infection affected neuronal differentiation and

  14. Stat5 Exerts Distinct, Vital Functions in the Cytoplasm and Nucleus of Bcr-Abl{sup +} K562 and Jak2(V617F){sup +} HEL Leukemia Cells

    Weber, Axel [Georg-Speyer-Haus, Institute for Tumor Biology and Experimental Therapy, Frankfurt am Main 60596 (Germany); Borghouts, Corina [Ganymed Pharmaceuticals AG, Mainz 55131 (Germany); Brendel, Christian [Boston Children’s Hospital, Division of Hematology/Oncology, Boston, MA 02115 (United States); Moriggl, Richard [Ludwig Boltzmann Institute for Cancer Research (LBI-CR), Vienna 1090 (Austria); Delis, Natalia; Brill, Boris; Vafaizadeh, Vida; Groner, Bernd, E-mail: Groner@em.uni-frankfurt.de [Georg-Speyer-Haus, Institute for Tumor Biology and Experimental Therapy, Frankfurt am Main 60596 (Germany)

    2015-03-19

    Signal transducers and activators of transcription (Stats) play central roles in the conversion of extracellular signals, e.g., cytokines, hormones and growth factors, into tissue and cell type specific gene expression patterns. In normal cells, their signaling potential is strictly limited in extent and duration. The persistent activation of Stat3 or Stat5 is found in many human tumor cells and contributes to their growth and survival. Stat5 activation plays a pivotal role in nearly all hematological malignancies and occurs downstream of oncogenic kinases, e.g., Bcr-Abl in chronic myeloid leukemias (CML) and Jak2(V617F) in other myeloproliferative diseases (MPD). We defined the mechanisms through which Stat5 affects growth and survival of K562 cells, representative of Bcr-Abl positive CML, and HEL cells, representative for Jak2(V617F) positive acute erythroid leukemia. In our experiments we suppressed the protein expression levels of Stat5a and Stat5b through shRNA mediated downregulation and demonstrated the dependence of cell survival on the presence of Stat5. Alternatively, we interfered with the functional capacities of the Stat5 protein through the interaction with a Stat5 specific peptide ligand. This ligand is a Stat5 specific peptide aptamer construct which comprises a 12mer peptide integrated into a modified thioredoxin scaffold, S5-DBD-PA. The peptide sequence specifically recognizes the DNA binding domain (DBD) of Stat5. Complex formation of S5-DBD-PA with Stat5 causes a strong reduction of P-Stat5 in the nuclear fraction of Bcr-Abl-transformed K562 cells and a suppression of Stat5 target genes. Distinct Stat5 mediated survival mechanisms were detected in K562 and Jak2(V617F)-transformed HEL cells. Stat5 is activated in the nuclear and cytosolic compartments of K562 cells and the S5-DBD-PA inhibitor most likely affects the viability of Bcr-Abl{sup +} K562 cells through the inhibition of canonical Stat5 induced target gene transcription. In HEL cells

  15. Perfect 3-dimensional lattice actions for 4-dimensional quantum field theories at finite temperature

    Kerres, U.; Mack, G.; Palma, G.

    1994-12-01

    We propose a two-step procedure to study the order of phase transitions at finite temperature in electroweak theory and in simplified models thereof. In a first step a coarse grained free energy is computed by perturbative methods. It is obtained in the form of a 3-dimensional perfect lattice action by a block spin transformation. It has finite temperature dependent coefficients. In this way the UV-problem and the infrared problem is separated in a clean way. In the second step the effective 3-dimensional lattice theory is treated in a nonperturbative way, either by the Feynman-Bololiubov method (solution of a gap equation), by real space renormalization group methods, or by computer simulations. In this paper we outline the principles for φ 4 -theory and scalar electrodynamics. The Balaban-Jaffe block spin transformation for the gauge field is used. It is known how to extend this transformation to the nonabelian case, but this will not be discussed here. (orig.)

  16. Evaluation of applicability of lead damper to 3-dimensional isolation system based on loading tests

    Matsuda, Akihiro

    2003-01-01

    To develop a damper for 3-dimensional base isolation system, horizontal and vertical mechanical properties, effect of loading frequency on vertical mechanical properties, coupled properties between horizontal and vertical directions, stability performance due to cyclic deformation are evaluated experimentally using scale models of lead damper originally developed for horizontal base isolation system. Loading test results are summarized as follows; 1) The lead damper has good vertical damping performance, in that the vertical yield load of the lead damper is three times as large as that for the horizontal direction, and the lead damper shows plastic behavior in the small deformation region. 2) The lead damper shows enough stability for static vertical displacement of ±40 mm. 3) the lead damper shows high stability performance for dynamic cyclic loading test using motions of isolation layer calculated by earthquake response analysis of FBR building subjected to S2-earthquake motion. Thus, applicability of the lead damper to 3-dimensional isolation system is shown from these results. (author)

  17. Automated, non-linear registration between 3-dimensional brain map and medical head image

    Mizuta, Shinobu; Urayama, Shin-ichi; Zoroofi, R.A.; Uyama, Chikao

    1998-01-01

    In this paper, we propose an automated, non-linear registration method between 3-dimensional medical head image and brain map in order to efficiently extract the regions of interest. In our method, input 3-dimensional image is registered into a reference image extracted from a brain map. The problems to be solved are automated, non-linear image matching procedure, and cost function which represents the similarity between two images. Non-linear matching is carried out by dividing the input image into connected partial regions, transforming the partial regions preserving connectivity among the adjacent images, evaluating the image similarity between the transformed regions of the input image and the correspondent regions of the reference image, and iteratively searching the optimal transformation of the partial regions. In order to measure the voxelwise similarity of multi-modal images, a cost function is introduced, which is based on the mutual information. Some experiments using MR images presented the effectiveness of the proposed method. (author)

  18. The anatomy of the aging face: volume loss and changes in 3-dimensional topography.

    Coleman, Sydney R; Grover, Rajiv

    2006-01-01

    Facial aging reflects the dynamic, cumulative effects of time on the skin, soft tissues, and deep structural components of the face, and is a complex synergy of skin textural changes and loss of facial volume. Many of the facial manifestations of aging reflect the combined effects of gravity, progressive bone resorption, decreased tissue elasticity, and redistribution of subcutaneous fullness. A convenient method for assessing the morphological effects of aging is to divide the face into the upper third (forehead and brows), middle third (midface and nose), and lower third (chin, jawline, and neck). The midface is an important factor in facial aesthetics because perceptions of facial attractiveness are largely founded on the synergy of the eyes, nose, lips, and cheek bones (central facial triangle). For aesthetic purposes, this area should be considered from a 3-dimensional rather than a 2-dimensional perspective, and restoration of a youthful 3-dimensional facial topography should be regarded as the primary goal in facial rejuvenation. Recent years have seen a significant increase in the number of nonsurgical procedures performed for facial rejuvenation. Patients seeking alternatives to surgical procedures include those who require restoration of lost facial volume, those who wish to enhance normal facial features, and those who want to correct facial asymmetry. Important factors in selecting a nonsurgical treatment option include the advantages of an immediate cosmetic result and a short recovery time.

  19. Candidate gene analyses of 3-dimensional dentoalveolar phenotypes in subjects with malocclusion

    Weaver, Cole A.; Miller, Steven F.; da Fontoura, Clarissa S. G.; Wehby, George L.; Amendt, Brad A.; Holton, Nathan E.; Allareddy, Veeratrishul; Southard, Thomas E.; Moreno Uribe, Lina M.

    2017-01-01

    Introduction Genetic studies of malocclusion etiology have identified 4 deleterious mutations in genes, DUSP6, ARHGAP21, FGF23, and ADAMTS1 in familial Class III cases. Although these variants may have large impacts on Class III phenotypic expression, their low frequency (malocclusions. Thus, much of the genetic variation underlying the dentofacial phenotypic variation associated with malocclusion remains unknown. In this study, we evaluated associations between common genetic variations in craniofacial candidate genes and 3-dimensional dentoalveolar phenotypes in patients with malocclusion. Methods Pretreatment dental casts or cone-beam computed tomographic images from 300 healthy subjects were digitized with 48 landmarks. The 3-dimensional coordinate data were submitted to a geometric morphometric approach along with principal component analysis to generate continuous phenotypes including symmetric and asymmetric components of dentoalveolar shape variation, fluctuating asymmetry, and size. The subjects were genotyped for 222 single-nucleotide polymorphisms in 82 genes/loci, and phenotpye-genotype associations were tested via multivariate linear regression. Results Principal component analysis of symmetric variation identified 4 components that explained 68% of the total variance and depicted anteroposterior, vertical, and transverse dentoalveolar discrepancies. Suggestive associations (P eruptions. Suggestive associations were found with TBX1 AJUBA, SNAI3 SATB2, TP63, and 1p22.1. Fluctuating asymmetry was associated with BMP3 and LATS1. Associations for SATB2 and BMP3 with asymmetric variations remained significant after the Bonferroni correction (P malocclusions were identified. PMID:28257739

  20. Myocardial Deformation Measured by 3-Dimensional Speckle Tracking in Children and Adolescents With Systemic Arterial Hypertension.

    Navarini, Susanne; Bellsham-Revell, Hannah; Chubb, Henry; Gu, Haotian; Sinha, Manish D; Simpson, John M

    2017-12-01

    Systemic arterial hypertension predisposes children to cardiovascular risk in childhood and adult life. Despite extensive study of left ventricular (LV) hypertrophy, detailed 3-dimensional strain analysis of cardiac function in hypertensive children has not been reported. The aim of this study was to evaluate LV mechanics (strain, twist, and torsion) in young patients with hypertension compared with a healthy control group and assess factors associated with functional measurements. Sixty-three patients (26 hypertension and 37 normotensive) were enrolled (mean age, 14.3 and 11.4 years; 54% men and 41% men, respectively). All children underwent clinical evaluation and echocardiographic examination, including 3-dimensional strain. There was no difference in LV volumes and ejection fraction between the groups. Myocardial deformation was significantly reduced in those with hypertension compared with controls. For hypertensive and normotensive groups, respectively, global longitudinal strain was -15.1±2.3 versus -18.5±1.9 ( P hypertensive and normotensive children, but children with hypertension had significantly lower strain indices. Whether reduced strain might predict future cardiovascular risk merits further longitudinal study. © 2017 American Heart Association, Inc.

  1. Physical properties of root cementum: Part I. A new method for 3-dimensional evaluation.

    Malek, S; Darendeliler, M A; Swain, M V

    2001-08-01

    Cementum is a nonuniform connective tissue that covers the roots of human teeth. Investigation of the physical properties of cementum may help in understanding or evaluating any possible connection to root resorption. A variety of engineering tests are available to investigate these properties. However, the thickness of the cementum layer varies, and this limits the applicability of these techniques in determining the physical properties of cementum. Hardness testing with Knoop and Vickers indentations overcame some of these limitations, but they prohibited the retrieval and retesting of the sample and therefore the testing was restricted to one area or section of the tooth. Another limiting factor with the existing techniques was the risk of artifacts related to the embedding material such as acrylic. A new method to investigate the physical properties of human premolar cementum was developed to obtain a 3-dimensional map of these properties with the Ultra Micro Indentation System (UMIS-2000; Commonwealth Scientific and Industrial Research Organization, Campbell, Australia). UMIS-2000 is a nano-indentation instrument for investigation of the properties of the near-surface region of materials. Premolars were harvested from orthodontic patients requiring extractions and then mounted on a newly designed surveyor that allowed sample retrieval and 3-dimensional rotation. This novel method enabled the quantitative testing of root surface cementum, on all 4 root surfaces, extending from the apex to the cementoenamel junction at 60 different sites.

  2. Gemcitabine resistance in breast cancer cells regulated by PI3K/AKT-mediated cellular proliferation exerts negative feedback via the MEK/MAPK and mTOR pathways

    Yang XL

    2014-06-01

    Full Text Available Xiao Li Yang, Feng Juan Lin, Ya Jie Guo, Zhi Min Shao, Zhou Luo Ou Key Laboratory of Breast Cancer in Shanghai, Breast Cancer Institute, Cancer Hospital, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China Abstract: Chemoresistance is a major cause of cancer treatment failure and leads to a reduction in the survival rate of cancer patients. Phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR and mitogen-activated protein kinase (MAPK pathways are aberrantly activated in many malignant tumors, including breast cancer, which may indicate an association with breast cancer chemoresistance. In this study, we generated a chemoresistant human breast cancer cell line, MDA-MB-231/gemcitabine (simplified hereafter as “231/Gem”, from MDA-MB-231 human breast cancer cells. Flow cytometry studies revealed that with the same treatment concentration of gemcitabine, 231/Gem cells displayed more robust resistance to gemcitabine, which was reflected by fewer apoptotic cells and enhanced percentage of S-phase cells. Through the use of inverted microscopy, Cell Counting Kit-8, and Transwell assays, we found that compared with parental 231 cells, 231/Gem cells displayed more morphologic projections, enhanced cell proliferative ability, and improved cell migration and invasion. Mechanistic studies revealed that the PI3K/AKT/mTOR and mitogen-activated protein kinase kinase (MEK/MAPK signaling pathways were activated through elevated expression of phosphorylated (p-extracellular signal-regulated kinase (ERK, p-AKT, mTOR, p-mTOR, p-P70S6K, and reduced expression of p-P38 and LC3-II (the marker of autophagy in 231/Gem in comparison to control cells. However, there was no change in the expression of Cyclin D1 and p-adenosine monophosphate-activated protein kinase (AMPK. In culture, inhibitors of PI3K/AKT and mTOR, but not of MEK/MAPK, could reverse the enhanced proliferative

  3. The value of preoperative 3-dimensional over 2-dimensional valve analysis in predicting recurrent ischemic mitral regurgitation after mitral annuloplasty

    Wijdh-den Hamer, Inez J.; Bouma, Wobbe; Lai, Eric K.; Levack, Melissa M.; Shang, Eric K.; Pouch, Alison M.; Eperjesi, Thomas J.; Plappert, Theodore J.; Yushkevich, Paul A.; Hung, Judy; Mariani, Massimo A.; Khabbaz, Kamal R.; Gleason, Thomas G.; Mahmood, Feroze; Acker, Michael A.; Woo, Y. Joseph; Cheung, Albert T.; Gillespie, Matthew J.; Jackson, Benjamin M.; Gorman, Joseph H.; Gorman, Robert C.

    Objectives: Repair for ischemic mitral regurgitation with undersized annuloplasty is characterized by high recurrence rates. We sought to determine the value of pre-repair 3-dimensional echocardiography over 2-dimensional echocardiography in predicting recurrence at 6 months. Methods: Intraoperative

  4. Facile Preparation of Carbon-Nanotube-based 3-Dimensional Transparent Conducting Networks for Flexible Noncontact Sensing Device

    Tai, Yanlong; Lubineau, Gilles

    2016-01-01

    Here, we report the controllable fabrication of transparent conductive films (TCFs) for moisture-sensing applications based on heating-rate-triggered, 3-dimensional porous conducting networks of single-walled carbon nanotube (SWCNT)/poly(3

  5. Skipjack tuna (Katsuwonus pelamis) eyeball oil exerts an anti-inflammatory effect by inhibiting NF-κB and MAPK activation in LPS-induced RAW 264.7 cells and croton oil-treated mice.

    Jeong, Da-Hyun; Kim, Koth-Bong-Woo-Ri; Kim, Min-Ji; Kang, Bo-Kyeong; Ahn, Dong-Hyun

    2016-11-01

    The effect of tuna eyeball oil (TEO) on lipopolysaccharide (LPS)-induced inflammation in macrophage cells was investigated. TEO had no cytotoxicity in cell viability as compared to the control in LPS induced RAW 264.7 cells. TEO reduced the levels of NO and pro-inflammatory cytokines by up to 50% in a dose-dependent manner. The expression of NF-κB and MAPKs as well as iNOS and COX-2 proteins was reduced by TEO, which suggests that its anti-inflammatory activity is related to the suppression of the NF-κB and MAPK signaling pathways. The rate of formation of ear edema was reduced compared to that in the control at the highest dose tested. In an acute toxicity test, no mice were killed by TEO doses of up to 5000mg/kg body weight during the two week observation period. These results suggested that TEO may have a significant effect on inflammatory factors and be a potential anti-inflammatory therapeutic. Copyright © 2016 Elsevier B.V. All rights reserved.

  6. Foxg1 regulates retinal axon pathfinding by repressing an ipsilateral program in nasal retina and by causing optic chiasm cells to exert a net axonal growth-promoting activity.

    Tian, Natasha M; Pratt, Thomas; Price, David J

    2008-12-01

    Mammalian binocular vision relies on the divergence of retinal ganglion cell axons at the optic chiasm, with strictly controlled numbers projecting contralaterally and ipsilaterally. In mouse, contralateral projections arise from the entire retina, whereas ipsilateral projections arise from ventrotemporal retina. We investigate how development of these patterns of projection is regulated by the contralateral determinant Foxg1, a forkhead box transcription factor expressed in nasal retina and at the chiasm. In nasal retina, loss of Foxg1 causes increased numbers of ipsilateral projections and ectopic expression of the ipsilateral determinants Zic2, Ephb1 and Foxd1, indicating that nasal retina is competent to express an ipsilateral program that is normally suppressed by Foxg1. Using co-cultures that combine Foxg1-expressing with Foxg1-null retinal explants and chiasm cells, we provide functional evidence that Foxg1 promotes contralateral projections through actions in nasal retina, and that in chiasm cells, Foxg1 is required for the generation of a hitherto unrecognized activity supporting RGC axon growth.

  7. Morphometric analysis of the femur in cerebral palsy: 3-dimensional CT study.

    Gose, Shinichi; Sakai, Takashi; Shibata, Toru; Murase, Tsuyoshi; Yoshikawa, Hideki; Sugamoto, Kazuomi

    2010-09-01

    The cause of hip disorder in cerebral palsy (CP) has been thought to involve muscle imbalance, flexion, and adduction contracture of the hip joint, acetabular dysplasia, and femoral growth abnormalities. The aim of this study was to quantitatively evaluate the 3-dimensional femoral geometry and subluxation/dislocation of the hip in spastic CP using 3D-CT reconstructed images of the pelvis and the femur, focusing on the femoral growth abnormalities in CP. Between June 2006 and September 2009, 186 hips in 93 bilateral spastic CP patients, including spastic diplegia (SD) in 73 patients and spastic quadriplegia (SQ) in 20 patients, who had not received any surgical treatment, were investigated using 3D-CT at our hospital. There were 59 boys and 34 girls with an average age of 5.3 years (range: 2.6 to 6.8 y). As an index for the femoral geometry, the neck-shaft angle, the femoral anteversion, and the femoral offset were 3-dimensionally measured. The center of the acetabulum and the femoral head were determined to calculate the CT migration percentage as the distance between these centers divided by the femoral head diameter. To elucidate the factors related to hip subluxation/dislocation, the relationships between the neck-shaft angle, the femoral anteversion, the femoral offset, and the CT migration percentage were investigated. The mean neck-shaft angle was 150.4+/-9.4 degrees (range: 129.4 to 173.2 degrees). The mean femoral anteversion was 44.4+/-13.6 degrees (range: 5.8 to 84.0 degrees). The mean CT migration percentage was 22.4+/-22.7% (range: 3 to 129%). There was positive correlation between the CT migration percentage and the neck-shaft angle (r=0.49). Hips with large CT migration percentage tended to show coxa valga. There was an inverse correlation between the neck-shaft angle and the femoral offset (r=-0.90), but no correlation between the CT migration percentage and the femoral anteversion (r=0.26), between the femoral offset and the femoral anteversion (r

  8. Photoprotection by pistachio bioactives in a 3-dimensional human skin equivalent tissue model.

    Chen, C-Y Oliver; Smith, Avi; Liu, Yuntao; Du, Peng; Blumberg, Jeffrey B; Garlick, Jonathan

    2017-09-01

    Reactive oxygen species (ROS) generated during ultraviolet (UV) light exposure can induce skin damage and aging. Antioxidants can provide protection against oxidative injury to skin via "quenching" ROS. Using a validated 3-dimensional (3D) human skin equivalent (HSE) tissue model that closely mimics human skin, we examined whether pistachio antioxidants could protect HSE against UVA-induced damage. Lutein and γ-tocopherol are the predominant lipophilic antioxidants in pistachios; treatment with these compounds prior to UVA exposure protected against morphological changes to the epithelial and connective tissue compartments of HSE. Pistachio antioxidants preserved overall skin thickness and organization, as well as fibroblast morphology, in HSE exposed to UVA irradiation. However, this protection was not substantiated by the analysis of the proliferation of keratinocytes and apoptosis of fibroblasts. Additional studies are warranted to elucidate the basis of these discordant results and extend research into the potential role of pistachio bioactives promoting skin health.

  9. Development of 6-axis portable manipulator which traces over 3-dimensional curved surface for ultrasonic inspection

    Hayashi, Tetsuji; Tsuzuki, Satoshi; Tsunewaki, Hiroshi.

    1993-01-01

    A 6-axis portable manipulator, weighing 120 N (12.3 kg) which traces over a 3-dimensional curved surface for ultrasonic testing has been developed. The manipulator body is made of carbon-fiber-reinforced plastic and magnesium alloy. A feature of the system is that deviation of the manipulator from its nominal path caused by arm bending due to its own weight can be corrected. The deviation is calculated by premeasuring spring coefficients and hysteresis characteristics of the arm structure. In a mock-up calibration performance test the accuracy was shown to be as high as that of a human inspector. The manipulator can be installed within 3 minutes by a single person. Joint angles are calculated with a direct memory access (DMA) handler using a poling method. Signals are transmitted to servo-controllers through an optical fiber of 2.5 Mbps. (author)

  10. Renormalization group aspects of 3-dimensional Pure U(1) lattice gauge theory

    Gopfert, M.; Mack, G.

    1983-01-01

    A few surprises in a recent study of the 3-dimensional pure U(1) lattice gauge theory model, from the point of view of the renormalization group theory, are discussed. Since the gauge group U(1) of this model is abelian, the model is subject to KramersWannier duality transformation. One obtains a ferromagnet with a global symmetry group Z. The duality transformation shows that the surface tension alpha of the model equals the strong tension of the U(1) gauge model. A theorem to represent the true asymptotic behaviour of alpha is derived. A second theorem considers the correlation functions. Discrepiancies between the theorems result in a solution that ''is regarded as a catastrophe'' in renormalization group theory. A lesson is drawn: To choose a good block spin in a renormalization group procedure, know what the low lying excitations of the theory are, to avoid integrating some of them by mischief

  11. 3-dimensional numerical modelling of rolling of superconducting Ag/BSCCO tape

    Eriksen, Morten; Bech, Jakob Ilsted; Seifi, Behrouz

    2000-01-01

    and Ø126 mm) have been investigated. It is found that it is possible to perform numerical simulation with 3D models of flat rolling of multifilament wire. Two 3D models have been used; 3D pressing with rolls and 3D rolling. 3D pressing with rolls have the advance that the simulation time is lower than...... in the 3D rolling. The 3D models have the advantage compared to 2D pressing that they can predict the 3 dimensional flow in the flat rolling, which has been showed to be very imported for the super conduction properties......Numerical simulation of the deformation process during flat rolling of multifilament HTS tapes has been investigated using a commercial FEM program, ELFEN. The numerical models were built up in 2D and 3D using a Drucker-Prager/Cap model for the powder. Three different roll diameters (Ø24 mm, Ø85 mm...

  12. Accuracy of 3-dimensional curvilinear measurements on digital models with intraoral scanners.

    Mack, Spencer; Bonilla, Tammy; English, Jeryl D; Cozad, Benjamin; Akyalcin, Sercan

    2017-09-01

    Our objectives were to evaluate and compare the digital dental models generated from 2 commercial intraoral scanners with manual measurements when performing 3-dimensional surface measurements along a curved line (curvilinear). Dry mandibles (n = 61) with intact dentition were used. The mandibles were digitized using 2 chair-side intraoral scanners: Cadent iTero (Align Technology, San Jose, Calif) and Lythos Digital Impression system (Ormco, Orange, Calif). Digitized 3-dimensional models were converted to individual stereolithography files and used with commercial software to obtain the curvilinear measurements. Manual measurements were carried out directly on the mandibular teeth. Measurements were made on different locations on the dental arch in various directions. One-sample t tests and linear regression analyses were performed. To further graphically examine the accuracy between the different methods, Bland-Altman plots were computed. The level of significance was set at P 0.05). Bland-Altman analysis showed no fixed bias of 1 approach vs the other, and random errors were detected in all comparisons. Although the mean biases of the digital models obtained by the iTero and Lythos scanners, when compared with direct caliper measurements, were low, the comparison of the 2 intraoral scanners yielded the lowest mean bias. No comparison displayed statistical significance for the t scores; this indicated the absence of proportional bias in these comparisons. The intraoral scanners tested in this study produced digital dental models that were comparatively accurate when performing direct surface measurements along a curved line in 3 dimensions. Copyright © 2017 American Association of Orthodontists. Published by Elsevier Inc. All rights reserved.

  13. Effect of dental technician disparities on the 3-dimensional accuracy of definitive casts.

    Emir, Faruk; Piskin, Bulent; Sipahi, Cumhur

    2017-03-01

    Studies that evaluated the effect of dental technician disparities on the accuracy of presectioned and postsectioned definitive casts are lacking. The purpose of this in vitro study was to evaluate the accuracy of presectioned and postsectioned definitive casts fabricated by different dental technicians by using a 3-dimensional computer-aided measurement method. An arch-shaped metal master model consisting of 5 abutments resembling prepared mandibular incisors, canines, and first molars and with a 6-degree total angle of convergence was designed and fabricated by computer-aided design and computer-aided manufacturing (CAD-CAM) technology. Complete arch impressions were made (N=110) from the master model, using polyvinyl siloxane (PVS) and delivered to 11 dental technicians. Each technician fabricated 10 definitive casts with dental stone, and the obtained casts were numbered. All casts were sectioned, and removable dies were obtained. The master model and the presectioned and postsectioned definitive casts were digitized with an extraoral scanner, and the virtual master model and virtual presectioned and postsectioned definitive casts were obtained. All definitive casts were compared with the master model by using computer-aided measurements, and the 3-dimensional accuracy of the definitive casts was determined with best fit alignment and represented in color-coded maps. Differences were analyzed using univariate analyses of variance, and the Tukey honest significant differences post hoc tests were used for multiple comparisons (α=.05). The accuracy of presectioned and postsectioned definitive casts was significantly affected by dental technician disparities (Ptechnician differences. Copyright © 2016 Editorial Council for the Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.

  14. The virtual nose: a 3-dimensional virtual reality model of the human nose.

    Vartanian, A John; Holcomb, Joi; Ai, Zhuming; Rasmussen, Mary; Tardy, M Eugene; Thomas, J Regan

    2004-01-01

    The 3-dimensionally complex interplay of soft tissue, cartilaginous, and bony elements makes the mastery of nasal anatomy difficult. Conventional methods of learning nasal anatomy exist, but they often involve a steep learning curve. Computerized models and virtual reality applications have been used to facilitate teaching in a number of other complex anatomical regions, such as the human temporal bone and pelvic floor. We present a 3-dimensional (3-D) virtual reality model of the human nose. Human cadaveric axial cross-sectional (0.33-mm cuts) photographic data of the head and neck were used. With 460 digitized images, individual structures were traced and programmed to create a computerized polygonal model of the nose. Further refinements to this model were made using a number of specialized computer programs. This 3-D computer model of the nose was then programmed to operate as a virtual reality model. Anatomically correct 3-D model of the nose was produced. High-resolution images of the "virtual nose" demonstrate the nasal septum, lower lateral cartilages, middle vault, bony dorsum, and other structural details of the nose. Also, the model can be combined with a separate virtual reality model of the face and its skin cover as well as the skull. The user can manipulate the model in space, examine 3-D anatomical relationships, and fade superficial structures to reveal deeper ones. The virtual nose is a 3-D virtual reality model of the nose that is accurate and easy to use. It can be run on a personal computer or in a specialized virtual reality environment. It can serve as an effective teaching tool. As the first virtual reality model of the nose, it establishes a virtual reality platform from which future applications can be launched.

  15. The effectiveness of an interactive 3-dimensional computer graphics model for medical education.

    Battulga, Bayanmunkh; Konishi, Takeshi; Tamura, Yoko; Moriguchi, Hiroki

    2012-07-09

    Medical students often have difficulty achieving a conceptual understanding of 3-dimensional (3D) anatomy, such as bone alignment, muscles, and complex movements, from 2-dimensional (2D) images. To this end, animated and interactive 3-dimensional computer graphics (3DCG) can provide better visual information to users. In medical fields, research on the advantages of 3DCG in medical education is relatively new. To determine the educational effectiveness of interactive 3DCG. We divided 100 participants (27 men, mean (SD) age 17.9 (0.6) years, and 73 women, mean (SD) age 18.1 (1.1) years) from the Health Sciences University of Mongolia (HSUM) into 3DCG (n = 50) and textbook-only (control) (n = 50) groups. The control group used a textbook and 2D images, while the 3DCG group was trained to use the interactive 3DCG shoulder model in addition to a textbook. We conducted a questionnaire survey via an encrypted satellite network between HSUM and Tokushima University. The questionnaire was scored on a 5-point Likert scale from strongly disagree (score 1) to strongly agree (score 5). Interactive 3DCG was effective in undergraduate medical education. Specifically, there was a significant difference in mean (SD) scores between the 3DCG and control groups in their response to questionnaire items regarding content (4.26 (0.69) vs 3.85 (0.68), P = .001) and teaching methods (4.33 (0.65) vs 3.74 (0.79), P < .001), but no significant difference in the Web category. Participants also provided meaningful comments on the advantages of interactive 3DCG. Interactive 3DCG materials have positive effects on medical education when properly integrated into conventional education. In particular, our results suggest that interactive 3DCG is more efficient than textbooks alone in medical education and can motivate students to understand complex anatomical structures.

  16. Downregulation of the S1P Transporter Spinster Homology Protein 2 (Spns2 Exerts an Anti-Fibrotic and Anti-Inflammatory Effect in Human Renal Proximal Tubular Epithelial Cells

    Olivier Blanchard

    2018-05-01

    Full Text Available Sphingosine kinase (SK catalyses the formation of sphingosine 1-phosphate (S1P, which acts as a key regulator of inflammatory and fibrotic reactions, mainly via S1P receptor activation. Here, we show that in the human renal proximal tubular epithelial cell line HK2, the profibrotic mediator transforming growth factor β (TGFβ induces SK-1 mRNA and protein expression, and in parallel, it also upregulates the expression of the fibrotic markers connective tissue growth factor (CTGF and fibronectin. Stable downregulation of SK-1 by RNAi resulted in the increased expression of CTGF, suggesting a suppressive effect of SK-1-derived intracellular S1P in the fibrotic process, which is lost when SK-1 is downregulated. In a further approach, the S1P transporter Spns2, which is known to export S1P and thereby reduces intracellular S1P levels, was stably downregulated in HK2 cells by RNAi. This treatment decreased TGFβ-induced CTGF and fibronectin expression, and it abolished the strong induction of the monocyte chemotactic protein 1 (MCP-1 by the pro-inflammatory cytokines tumor necrosis factor (TNFα and interleukin (IL-1β. Moreover, it enhanced the expression of aquaporin 1, which is an important water channel that is expressed in the proximal tubules, and reverted aquaporin 1 downregulation induced by IL-1β/TNFα. On the other hand, overexpression of a Spns2-GFP construct increased S1P secretion and it resulted in enhanced TGFβ-induced CTGF expression. In summary, our data demonstrate that in human renal proximal tubular epithelial cells, SK-1 downregulation accelerates an inflammatory and fibrotic reaction, whereas Spns2 downregulation has an opposite effect. We conclude that Spns2 represents a promising new target for the treatment of tubulointerstitial inflammation and fibrosis.

  17. p19-targeted ABD-derived protein variants inhibit IL-23 binding and exert suppressive control over IL-23-stimulated expansion of primary human IL-17+T-cells

    Křížová, Lucie; Kuchař, Milan; Petroková, Hana; Osička, Radim; Hlavničková, Marie; Pelák, O.; Černý, Jiří; Kalina, T.; Malý, Petr

    2017-01-01

    Roč. 50, č. 2 (2017), s. 102-113 ISSN 0891-6934 R&D Projects: GA MZd(CZ) NV16-27676A; GA ČR GAP303/10/1849; GA ČR GA15-09157S; GA MŠk(CZ) ED1.1.00/02.0109 Institutional support: RVO:86652036 ; RVO:61388971 Keywords : Psoriasis * Th17 cell * IL-23 * protein binder Subject RIV: EC - Immunology; EC - Immunology (MBU-M) OBOR OECD: Immunology; Immunology (MBU-M) Impact factor: 2.629, year: 2016

  18. The definition of exertion-related cardiac events.

    Rai, M; Thompson, P D

    2011-02-01

    Vigorous physical activity increases the risk of sudden cardiac death (SCD) and acute myocardial infarction (AMI) but there is no standard definition as to what constitutes an exertion-related cardiac event, specifically the time interval between physical exertion and cardiac event. A systematic review of studies related to exertion-related cardiac events was performed and the time interval between exertion and the event or the symptoms leading to the event was looked for in all the articles selected for inclusion. A total of 12 of 26 articles "suggested" or "defined" exertion-related events as those events whose symptoms started during or within 1 h of exertion. Others used definitions of 0.5 h, 2 h, "during exertion", "during or immediately post exertion" and "during or within several hours after exertion". It is suggested, therefore, that the definition of an exertion-related cardiac event be established as a cardiac event in which symptoms started during or within 1 h of physical exertion.

  19. α-Methyl artoflavanocoumarin from Juniperus chinensis exerts anti-diabetic effects by inhibiting PTP1B and activating the PI3K/Akt signaling pathway in insulin-resistant HepG2 cells.

    Jung, Hee Jin; Seong, Su Hui; Ali, Md Yousof; Min, Byung-Sun; Jung, Hyun Ah; Choi, Jae Sue

    2017-12-01

    Diabetes mellitus is one of the greatest global health issues and much research effort continues to be directed toward identifying novel therapeutic agents. Insulin resistance is a challenging integrally related topic and molecules capable of overcoming it are of considerable therapeutic interest in the context of type 2 diabetes mellitus (T2DM). Protein tyrosine phosphatase 1B (PTP1B) negatively regulates insulin signaling transduction and is regarded a novel therapeutic target in T2DM. Here, we investigated the inhibitory effect of α-methyl artoflavanocoumarin (MAFC), a natural flavanocoumarin isolated from Juniperus chinensis, on PTP1B in insulin-resistant HepG2 cells. MAFC was found to potently inhibit PTP1B with an IC 50 of 25.27 ± 0.14 µM, and a kinetics study revealed MAFC is a mixed type PTP1B inhibitor with a K i value of 13.84 µM. Molecular docking simulations demonstrated MAFC can bind to catalytic and allosteric sites of PTP1B. Furthermore, MAFC significantly increased glucose uptake and decreased the expression of PTP1B in insulin-resistant HepG2 cells, down-regulated the phosphorylation of insulin receptor substrate (IRS)-1 (Ser307), and dose-dependently enhanced the protein levels of IRS-1, phosphorylated phosphoinositide 3-kinase (PI3K), Akt, and ERK1. These results suggest that MAFC from J. chinensis has therapeutic potential in T2DM by inhibiting PTP1B and activating insulin signaling pathways.

  20. Wine polyphenols exert antineoplasic effect on androgen resistant PC-3 cell line through the inhibition of the transcriptional activity of COX-2 promoter mediated by NF-kβ.

    Ferruelo, A; de Las Heras, M M; Redondo, C; Ramón de Fata, F; Romero, I; Angulo, J C

    2014-09-01

    Mediterranean diet may play a role in the prevention of prostate cancer (PCa) development and progression. Cyclooxygenase-2 (COX-2) expression is associated with increased cellular proliferation, prevents apoptosis and favors tumor invasion. We intend to clarify whether resveratrol and other polyphenols effectively inhibit COX-2 activity and induce apoptosis in hormone-resistant PC-3 cell line. PC-3 cells were cultured and treated with different concentrations of gallic acid, tannic acid, quercetin, and resveratrol in presence of phorbol myristate acetate (PMA; 50 μg/ml) that induces COX-2 expression. Total RNA was extracted and COX-2 expression was analyzed by relative quantification real-time PCR (ΔΔCt method). COX-2 activity was determined by PGE-2 detection using ELISA. Caspase 3/7 luminescence assay was used to disclose apoptosis. Transitory transfection with short human COX-2 (phPES2 -327/+59) and p5xNF-kβ-Luc plasmids determined COX-2 promoter activity and specifically that dependant of NF-kβ. COX-2 expression was not modified in media devoid of PMA. However, under PMA induction tannic acid (2.08 ±.21), gallic acid (2.46 ±.16), quercetin (1.78 ±.14) and resveratrol (1.15 ±.16) significantly inhibited COX-2 mRNA with respect to control (3.14 ±.07), what means a 34%, 23%, 46% and 61% reduction, respectively. The inhibition in the levels of PGE-2 followed a similar pattern. All compounds studied induced apoptosis at 48 h, although at a different rate. PMA caused a rise in activity 7.4 ±.23 times phPES2 -327/+59 and 2.0 ±.1 times p5xNF-kβ-Luc at 6h compared to basal. Resveratrol suppressed these effects 17.1 ±.21 and 32.4 ±.18 times, respectively. Similarly, but to a lesser extent, the rest of evaluated polyphenols diminished PMA inductor effect on the activity of both promoters. Polyphenols inhibit transcriptional activity of COX-2 promoter mediated by NF-kβ. This effect could explain, at least in part, the induction of apoptosis in vitro by

  1. Electro-acupuncture exerts beneficial effects against cerebral ischemia and promotes the proliferation of neural progenitor cells in the cortical peri-infarct area through the Wnt/β-catenin signaling pathway

    CHEN, BIN; TAO, JING; LIN, YUKUN; LIN, RUHUI; LIU, WEILIN; CHEN, LIDIAN

    2015-01-01

    Electro-acupuncture (EA) is a novel therapy based on combining traditional acupuncture with modern electrotherapy, and it is currently being investigated as a treatment for ischemic stroke. In the present study, we aimed to investigate the mechanisms through which EA regulates the proliferation of neural progenitor cells (NPCs) in the cortical peri-infarct area after stroke. The neuroprotective effects of EA on ischemic rats were evaluated by determining the neurological deficit scores and cerebral infarct volumes. The proliferation of the NPCs and the activation of the Wnt/β-catenin signaling pathway in the cortical peri-infarct area were examined. Our results revealed that EA significantly alleviated neurological deficits, reduced the infarct volume and enhanced NPC proliferation [nestin/glial fibrillary acidic protein (GFAP)-double positive] in the cortex of rats subjected to middle cerebral artery occlusion (MCAO). Moreover, the Wnt1 and β-catenin mRNA and protein levels were increased, while glycogen synthase kinase-3 (GSK3) transcription was suppressed by EA. These results suggest that the upregulatory effects of EA on the Wnt/β-catenin signaling pathway may promote NPC proliferation in the cortical peri-infarct area after stroke, consequently providing a therapeutic effect against cerebral ischemia. PMID:26329606

  2. The Investigation of Accuracy of 3 Dimensional Models Generated From Point Clouds with Terrestrial Laser Scanning

    Gumus, Kutalmis; Erkaya, Halil

    2013-04-01

    In Terrestrial laser scanning (TLS) applications, it is necessary to take into consideration the conditions that affect the scanning process, especially the general characteristics of the laser scanner, geometric properties of the scanned object (shape, size, etc.), and its spatial location in the environment. Three dimensional models obtained with TLS, allow determining the geometric features and relevant magnitudes of the scanned object in an indirect way. In order to compare the spatial location and geometric accuracy of the 3-dimensional model created by Terrestrial laser scanning, it is necessary to use measurement tools that give more precise results than TLS. Geometric comparisons are performed by analyzing the differences between the distances, the angles between surfaces and the measured values taken from cross-sections between the data from the 3-dimensional model created with TLS and the values measured by other measurement devices The performance of the scanners, the size and shape of the scanned objects are tested using reference objects the sizes of which are determined with high precision. In this study, the important points to consider when choosing reference objects were highlighted. The steps up to processing the point clouds collected by scanning, regularizing these points and modeling in 3 dimensions was presented visually. In order to test the geometric correctness of the models obtained by Terrestrial laser scanners, sample objects with simple geometric shapes such as cubes, rectangular prisms and cylinders that are made of concrete were used as reference models. Three dimensional models were generated by scanning these reference models with Trimble Mensi GS 100. The dimension of the 3D model that is created from point clouds was compared with the precisely measured dimensions of the reference objects. For this purpose, horizontal and vertical cross-sections were taken from the reference objects and generated 3D models and the proximity of

  3. Duplication of complete dentures using general-purpose handheld optical scanner and 3-dimensional printer: Introduction and clinical considerations.

    Kurahashi, Kosuke; Matsuda, Takashi; Goto, Takaharu; Ishida, Yuichi; Ito, Teruaki; Ichikawa, Tetsuo

    2017-01-01

    To introduce a new clinical procedure for fabricating duplicates of complete dentures by bite pressure impression using digital technology, and to discuss its clinical significance. The denture is placed on a rotary table and the 3-dimensional form of the denture is digitized using a general-purpose handheld optical scanner. The duplicate denture is made of polylactic acid by a 3-dimensional printer using the 3-dimensional data. This procedure has the advantages of wasting less material, employing less human power, decreasing treatment time at the chair side, lowering the rates of contamination, and being readily fabricated at the time of the treatment visit. Copyright © 2016 Japan Prosthodontic Society. Published by Elsevier Ltd. All rights reserved.

  4. An experimental study for qualitatively diagnosing stapes lesions by helical 3-dimensional CT

    Kawaue, Akifumi; Kuki, Kiyonori; Yamanaka, Noboru; Nishimura, Michihiko

    2001-01-01

    To evaluate qualitative diagnosis of stapes lesions by 3-dimensional computed tomography (3D-CT) combined with superselective image processing (3D-SS) of stapes, we studied helical 3D-CT on a phantom model of the temporal bone. Two stapes models were used-1 made from the bone filler, Celatite, consistent in bone density but changing in cross sectional area, and the other made from an apacerum rod used in quantitative computed tomography (QCT), consistent in cross sectional area but changing in bone density. These stapes models were put into a skull phantom and analyzed by helical 3D-CT. The influence of the tympanic cavity conditions on CT images of stapes was evaluated by filling the phantom model with Vaseline following 3D selective reconstruction. In all stapes models, lowering the lower CT window width threshold resulted in an enlarged cross-sectional area of the model. The higher the bone density, the lower the increase in cross-sectional area in the image. The stapes model with lower density had greater influence on the imaging by tympanic cavity conditions and was likely to be misdiagnosed as showing higher bone density. Based on the experimental study, 3D-SS by helical 3D-CT appears to be a useful measure for qualitatively diagnosing stapes lesions. (author)

  5. Polarized light microscopy for 3-dimensional mapping of collagen fiber architecture in ocular tissues.

    Yang, Bin; Jan, Ning-Jiun; Brazile, Bryn; Voorhees, Andrew; Lathrop, Kira L; Sigal, Ian A

    2018-04-06

    Collagen fibers play a central role in normal eye mechanics and pathology. In ocular tissues, collagen fibers exhibit a complex 3-dimensional (3D) fiber orientation, with both in-plane (IP) and out-of-plane (OP) orientations. Imaging techniques traditionally applied to the study of ocular tissues only quantify IP fiber orientation, providing little information on OP fiber orientation. Accurate description of the complex 3D fiber microstructures of the eye requires quantifying full 3D fiber orientation. Herein, we present 3dPLM, a technique based on polarized light microscopy developed to quantify both IP and OP collagen fiber orientations of ocular tissues. The performance of 3dPLM was examined by simulation and experimental verification and validation. The experiments demonstrated an excellent agreement between extracted and true 3D fiber orientation. Both IP and OP fiber orientations can be extracted from the sclera and the cornea, providing previously unavailable quantitative 3D measures and insight into the tissue microarchitecture. Together, the results demonstrate that 3dPLM is a powerful imaging technique for the analysis of ocular tissues. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. Systematic Review of the Use of 3-Dimensional Printing in Surgical Teaching and Assessment.

    Langridge, Benjamin; Momin, Sheikh; Coumbe, Ben; Woin, Evelina; Griffin, Michelle; Butler, Peter

    The use of 3-dimensional (3D) printing in medicine has rapidly expanded in recent years as the technology has developed. The potential uses of 3D printing are manifold. This article provides a systematic review of the uses of 3D printing within surgical training and assessment. A structured literature search of the major literature databases was performed in adherence to PRISMA guidelines. Articles that met predefined inclusion and exclusion criteria were appraised with respect to the key objectives of the review and sources of bias were analysed. Overall, 49 studies were identified for inclusion in the qualitative analysis. Heterogeneity in study design and outcome measures used prohibited meaningful meta-analysis. 3D printing has been used in surgical training across a broad range of specialities but most commonly in neurosurgery and otorhinolaryngology. Both objective and subjective outcome measures have been studied, demonstrating the usage of 3D printed models in training and education. 3D printing has also been used in anatomical education and preoperative planning, demonstrating improved outcomes when compared to traditional educational methods and improved patient outcomes, respectively. 3D printing technology has a broad range of potential applications within surgical education and training. Although the field is still in its relative infancy, several studies have already demonstrated its usage both instead of and in addition to traditional educational methods. Copyright © 2018 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.

  7. Development of sodium droplet combustion analysis methodology using direct numerical simulation in 3-dimensional coordinate (COMET)

    Okano, Yasushi; Ohira, Hiroaki

    1998-08-01

    In the early stage of sodium leak event of liquid metal fast breeder reactor, LMFBR, liquid sodium flows out from a piping, and ignition and combustion of liquid sodium droplet might occur under certain environmental condition. Compressible forced air flow, diffusion of chemical species, liquid sodium droplet behavior, chemical reactions and thermodynamic properties should be evaluated with considering physical dependence and numerical connection among them for analyzing combustion of sodium liquid droplet. A direct numerical simulation code was developed for numerical analysis of sodium liquid droplet in forced convection air flow. The numerical code named COMET, 'Sodium Droplet COmbustion Analysis METhodology using Direct Numerical Simulation in 3-Dimensional Coordinate'. The extended MAC method was used to calculate compressible forced air flow. Counter diffusion among chemical species is also calculated. Transport models of mass and energy between droplet and surrounding atmospheric air were developed. Equation-solving methods were used for computing multiphase equilibrium between sodium and air. Thermodynamic properties of chemical species were evaluated using dynamic theory of gases. Combustion of single sphere liquid sodium droplet in forced convection, constant velocity, uniform air flow was numerically simulated using COMET. Change of droplet diameter with time was closely agree with d 2 -law of droplet combustion theory. Spatial distributions of combustion rate and heat generation and formation, decomposition and movement of chemical species were analyzed. Quantitative calculations of heat generation and chemical species formation in spray combustion are enabled for various kinds of environmental condition by simulating liquid sodium droplet combustion using COMET. (author)

  8. Characterization of 3-dimensional superconductive thin film components for gravitational experiments in space

    Hechler, S.; Nawrodt, R.; Nietzsche, S.; Vodel, W.; Seidel, P. [Friedrich-Schiller-Univ. Jena (Germany). Inst. fuer Festkoerperphysik; Dittus, H. [ZARM, Univ. Bremen (Germany); Loeffler, F. [Physikalisch-Technische Bundesanstalt, Braunschweig (Germany)

    2007-07-01

    Superconducting quantum interference devices (SQUIDs) are used for high precise gravitational experiments. One of the most impressive experiments is the satellite test of the equivalence principle (STEP) of NASA/ESA. The STEP mission aims to prove a possible violation of Einstein's equivalence principle at an extreme level of accuracy of 1 part in 10{sup 18} in space. In this contribution we present an automatically working measurement equipment to characterize 3-dimensional superconducting thin film components like i.e. pick-up coils and test masses for STEP. The characterization is done by measurements of the transition temperature between the normal and the superconducting state using a special built anti-cryostat. Above all the setup was designed for use in normal LHe transport Dewars. The sample chamber has a volume of 150 cm{sup 3} and can be fully temperature controlled over a range from 4.2 K to 300 K with a resolution of better then 100 mK. (orig.)

  9. Relationship of maxillary 3-dimensional posterior occlusal plane to mandibular spatial position and morphology.

    Coro, Jorge C; Velasquez, Roberto L; Coro, Ivette M; Wheeler, Timothy T; McGorray, Susan P; Sato, Sadao

    2016-07-01

    The purpose of this study was to examine the relationship of the 3-dimensional (3D) posterior occlusal plane (POP) and the mandibular 3D spatial position. The relationship of the POP to mandibular morphology was also investigated. Retrospective data from a convenience sample of pretreatment diagnostic cone-beam computed tomography scans were rendered using InVivo software (Anatomage, San Jose, Calif). The sample consisted of 111 subjects (51 male, 60 female) and included growing and nongrowing subjects of different races and ethnicities. The 3D maxillary POP was defined by selecting the cusp tips of the second premolars and the second molars on the rendered images of the subjects. The angles made by this plane, in reference to the Frankfort horizontal plane, were measured against variables that described the mandibular position in the coronal, sagittal, and axial views. The POP was also compared with bilateral variables that described mandibular morphology. There were significant differences of the POP among the different skeletal malocclusions (P <0.0001). The POP showed significant correlations with mandibular position in the sagittal (P <0.0001), coronal (P <0.05), and axial (P <0.05) planes. The POP also showed a significant correlation with mandibular morphology (P <0.0001). These findings suggest that there is a distinct and significant relationship between the 3D POP and the mandibular spatial position and its morphology. Copyright © 2016 American Association of Orthodontists. Published by Elsevier Inc. All rights reserved.

  10. 3-DIMENSIONAL Numerical Modeling on the Combustion and Emission Characteristics of Biodiesel in Diesel Engines

    Yang, Wenming; An, Hui; Amin, Maghbouli; Li, Jing

    2014-11-01

    A 3-dimensional computational fluid dynamics modeling is conducted on a direct injection diesel engine fueled by biodiesel using multi-dimensional software KIVA4 coupled with CHEMKIN. To accurately predict the oxidation of saturated and unsaturated agents of the biodiesel fuel, a multicomponent advanced combustion model consisting of 69 species and 204 reactions combined with detailed oxidation pathways of methyl decenoate (C11H22O2), methyl-9-decenoate (C11H20O2) and n-heptane (C7H16) is employed in this work. In order to better represent the real fuel properties, the detailed chemical and thermo-physical properties of biodiesel such as vapor pressure, latent heat of vaporization, liquid viscosity and surface tension were calculated and compiled into the KIVA4 fuel library. The nitrogen monoxide (NO) and carbon monoxide (CO) formation mechanisms were also embedded. After validating the numerical simulation model by comparing the in-cylinder pressure and heat release rate curves with experimental results, further studies have been carried out to investigate the effect of combustion chamber design on flow field, subsequently on the combustion process and performance of diesel engine fueled by biodiesel. Research has also been done to investigate the impact of fuel injector location on the performance and emissions formation of diesel engine.

  11. The 3-Dimensional Fermi Liquid Description for the Iron-Based Superconductors

    Misawa, Setsuo

    2018-01-01

    The quasiparticles in the normal state of iron-based superconductors have been shown to behave universally as a 3-dimensional Fermi liquid. Because of interactions and the presence of sharp Fermi surfaces, the quasiparticle energy contains, as a function of the momentum \\varvec{p}, a term of the form ( p - p_0)^3 ln {( |p-p_0|/p_0)} , where p = | \\varvec{p} | and p_0 is the Fermi momentum. The electronic specific heat coefficient, magnetic susceptibility (Knight shift), electrical resistivity, Hall coefficient and thermoelectric power divided by temperature follow, as functions of temperature T, the logarithmic formula a-b T^2 ln {(T/T^*)}, a, b and T^* being constant; these formulae have been shown to explain the observed data for all iron-based superconductors. It is shown that the concept of non-Fermi liquids or anomalous metals which appears in the literature is not needed for descriptions of the present systems. When the superconducting transition temperature TC and the b / a value for the resistivity are plotted as functions of the doping content x, there appear various characteristic diagrams in which regions of positive correlation and those of negative correlation between TC and b / a are interconnected; from these diagrams, we may make speculations about the types of superconductivity and the crossover between them.

  12. Multilevel Spondylolysis Repair Using the "Smiley Face" Technique with 3-Dimensional Intraoperative Spinal Navigation.

    Voisin, Mathew R; Witiw, Christopher D; Deorajh, Ryan; Guha, Daipayan; Oremakinde, Adetunji; Wang, Shelly; Yang, Victor

    2018-01-01

    Multilevel spondylolysis is a rare cause of progressive lower back pain, and patients who fail conservative management are treated surgically. Direct repair methods can maintain mobility and lead to decreased morbidity compared with spinal fusion in single-level spondylolysis. In this paper, we present a patient with nonadjacent multilevel spondylolysis who underwent the "smiley face" technique of direct multilevel repair without fusion using 3-dimensional intraoperative spinal navigation. Bilateral spondylolysis at L3 and L5 with associated spondylolisthesis in a 50-year-old male was repaired using the "smiley face" technique. Patient-reported outcomes, including the Oswestry Disability Index (ODI) and visual analog scale scores for back and leg pain, were assessed preoperatively along with 6 weeks and 4 months postoperatively. Postoperative computed tomography imaging showed precise screw insertion and rod placement along with stable hardware alignment in follow-up imaging. The patient's ODI and lower back visual analog scale scores decreased from 25 to 8 and 7.5 to 4, respectively, correlating to an excellent outcome on ODI. Direct repair and avoidance of fusion is possible and can provide good functional outcomes in patients with nonadjacent multilevel spondylolysis and associated spondylolisthesis. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Advanced 3-dimensional electron kinetic calculations for the current drive problem in magnetically confined thermonuclear plasmas

    Peysson, Y.; Decker, J.; Bers, A.; Ram, A.; Harvey, R.

    2004-01-01

    Accurate and fast electron kinetic calculations is a challenging issue for realistic simulations of thermonuclear tokamak plasmas. Relativistic corrections and electron trajectory effects must be fully taken into account for high temperature burning plasmas, while codes should also consistently describe wave-particle resonant interactions in presence of locally large gradients close to internal transport barrier. In that case, neoclassical effects may come into play and self-consistent evaluation of both the radio-frequency and bootstrap currents must be performed. In addition, a complex interplay between momentum and radial electron dynamics may take place, in presence of a possible energy dependent radial transport. Besides the physics needs, there are considerable numerical issues to solve, in order to reduce computer time consumption and memory requirements at an acceptable level, so that kinetic calculations may be valuably incorporated in a chain of codes which determines plasma equilibrium and wave propagation. So far, fully implicit 3-dimensional calculations based on a finite difference scheme and an incomplete L and U matrices factorization have been found to be so most effective method to reach this goal. A review of the present status in this active field of physics is presented, with an emphasis on possible future improvements. (authors)

  14. Image-Based 3-Dimensional Characterization of Laryngotracheal Stenosis in Children

    Lee S. McDaniel PhD

    2018-01-01

    Full Text Available Objectives Describe a technique for the description and classification of laryngotracheal stenosis in children using 3-dimensional reconstructions of the airway from computed tomography (CT scans. Study Design Cross-sectional. Setting Academic tertiary care children’s hospital. Subjects and Methods Three-dimensional models of the subglottic airway lumen were created using CT scans from 54 children undergoing imaging for indications other than airway disease. The base lumen models were deformed in software to simulate subglottic airway segments with 0%, 25%, 50%, and 75% stenoses for each subject. Statistical analysis of the airway geometry was performed using metrics extracted from the lumen centerlines. The centerline analysis was used to develop a system for subglottic stenosis assessment and classification from patient-specific airway imaging. Results The scaled hydraulic diameter gradient metric derived from intersectional changes in the lumen can be used to accurately classify and quantitate subglottic stenosis in the airway based on CT scan imaging. Classification is most accurate in the clinically relevant 25% to 75% range of stenosis. Conclusions Laryngotracheal stenosis is a complex diagnosis requiring an understanding of the airway lumen configuration, anatomical distortions of the airway framework, and alterations of respiratory aerodynamics. Using image-based airway models, we have developed a metric that accurately captures subglottis patency. While not intended to replace endoscopic evaluation and existing staging systems for laryngotracheal stenosis, further development of these techniques will facilitate future studies of upper airway computational fluid dynamics and the clinical evaluation of airway disease.

  15. Casting of 3-dimensional footwear prints in snow with foam blocks.

    Petraco, Nicholas; Sherman, Hal; Dumitra, Aurora; Roberts, Marcel

    2016-06-01

    Commercially available foam blocks are presented as an alternative material for the casting and preservation of 3-dimensional footwear impressions located in snow. The method generates highly detailed foam casts of questioned footwear impressions. These casts can be compared to the known outsole standards made from the suspects' footwear. Modification of the commercially available foam casting blocks is simple and fast. The foam block is removed and a piece of cardboard is secured to one side of the block with painter's masking tape. The prepared foam block is then placed back into its original box, marked appropriately, closed and stored until needed. When required the foam block is carefully removed from its storage box and gently placed, foam side down, over the questioned footwear impression. Next, the crime scene technician's hands are placed on top of the cardboard and pressure is gently applied by firmly pressing down onto the impression. The foam cast is removed, dried and placed back into its original container and sealed. The resulting 3D impressions can be directly compared to the outsole of known suspected item(s) of footwear. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  16. Real-time interpolation for true 3-dimensional ultrasound image volumes.

    Ji, Songbai; Roberts, David W; Hartov, Alex; Paulsen, Keith D

    2011-02-01

    We compared trilinear interpolation to voxel nearest neighbor and distance-weighted algorithms for fast and accurate processing of true 3-dimensional ultrasound (3DUS) image volumes. In this study, the computational efficiency and interpolation accuracy of the 3 methods were compared on the basis of a simulated 3DUS image volume, 34 clinical 3DUS image volumes from 5 patients, and 2 experimental phantom image volumes. We show that trilinear interpolation improves interpolation accuracy over both the voxel nearest neighbor and distance-weighted algorithms yet achieves real-time computational performance that is comparable to the voxel nearest neighbor algrorithm (1-2 orders of magnitude faster than the distance-weighted algorithm) as well as the fastest pixel-based algorithms for processing tracked 2-dimensional ultrasound images (0.035 seconds per 2-dimesional cross-sectional image [76,800 pixels interpolated, or 0.46 ms/1000 pixels] and 1.05 seconds per full volume with a 1-mm(3) voxel size [4.6 million voxels interpolated, or 0.23 ms/1000 voxels]). On the basis of these results, trilinear interpolation is recommended as a fast and accurate interpolation method for rectilinear sampling of 3DUS image acquisitions, which is required to facilitate subsequent processing and display during operating room procedures such as image-guided neurosurgery.

  17. Scaling Relations and Self-Similarity of 3-Dimensional Reynolds-Averaged Navier-Stokes Equations.

    Ercan, Ali; Kavvas, M Levent

    2017-07-25

    Scaling conditions to achieve self-similar solutions of 3-Dimensional (3D) Reynolds-Averaged Navier-Stokes Equations, as an initial and boundary value problem, are obtained by utilizing Lie Group of Point Scaling Transformations. By means of an open-source Navier-Stokes solver and the derived self-similarity conditions, we demonstrated self-similarity within the time variation of flow dynamics for a rigid-lid cavity problem under both up-scaled and down-scaled domains. The strength of the proposed approach lies in its ability to consider the underlying flow dynamics through not only from the governing equations under consideration but also from the initial and boundary conditions, hence allowing to obtain perfect self-similarity in different time and space scales. The proposed methodology can be a valuable tool in obtaining self-similar flow dynamics under preferred level of detail, which can be represented by initial and boundary value problems under specific assumptions.

  18. A customized bolus produced using a 3-dimensional printer for radiotherapy.

    Kim, Shin-Wook; Shin, Hun-Joo; Kay, Chul Seung; Son, Seok Hyun

    2014-01-01

    Boluses are used in high-energy radiotherapy in order to overcome the skin sparing effect. In practice though, commonly used flat boluses fail to make a perfect contact with the irregular surface of the patient's skin, resulting in air gaps. Hence, we fabricated a customized bolus using a 3-dimensional (3D) printer and evaluated its feasibility for radiotherapy. We designed two kinds of bolus for production on a 3D printer, one of which was the 3D printed flat bolus for the Blue water phantom and the other was a 3D printed customized bolus for the RANDO phantom. The 3D printed flat bolus was fabricated to verify its physical quality. The resulting 3D printed flat bolus was evaluated by assessing dosimetric parameters such as D1.5 cm, D5 cm, and D10 cm. The 3D printed customized bolus was then fabricated, and its quality and clinical feasibility were evaluated by visual inspection and by assessing dosimetric parameters such as Dmax, Dmin, Dmean, D90%, and V90%. The dosimetric parameters of the resulting 3D printed flat bolus showed that it was a useful dose escalating material, equivalent to a commercially available flat bolus. Analysis of the dosimetric parameters of the 3D printed customized bolus demonstrated that it is provided good dose escalation and good contact with the irregular surface of the RANDO phantom. A customized bolus produced using a 3D printer could potentially replace commercially available flat boluses.

  19. Tunneling currents between carbon nanotubes inside the 3-dimensional potential of a dielectric matrix

    M. S. Tsagarakis

    2017-07-01

    Full Text Available We have examined the tunneling currents between CNTs dispersed in a dielectric matrix as is normally the case in a tensile stress or toxic gas sensors. Due to the randomness of the immersion process the CNTs are at random angles and configurations between them, thus producing a 3-dimensional potential (3-D. We have produced a method that solves the Laplace equation for this type of problem and uses the WKB formulation to calculate the transmission coefficient between CNTs. We have then shown that the tunneling currents between a pair of CNTs depend critically on their relative angle and configuration. In particular we have shown that the tunneling currents do not occur only along a CNT tip to CNT tip configuration but other more efficient paths exist which give a current higher by two orders of magnitude from what a simple 1D theory would give. On the other hand the tunneling current between non-coplanar CNTs is negligible. We conclude that such phenomena cannot be analyzed by a simple 1-dimensional WKB theory and the percolation threshold necessary for conduction may be lower than the one such a theory would predict.

  20. SBNCT plan: A 3-dimensional treatment planning system for boron neutron capture therapy

    Reinstein, L.E.; Ramsay, E.B.; Gajewski, J.; Ramamoorthy, S.; Meek, A.G.

    1993-01-01

    The need for accurate and comprehensive 3-dimensional treatment planning for boron neutron capture therapy (BNCT) has been debated for the past several years. Although many argue against the need for elaborate and expensive treatment planning programs which mimic conventional radiotherapy planning systems, it is clear that in order to realize significant gains over conventional fractionated radiation therapy, patients must be treated to the edge of normal tissue tolerance. Just how close to this edge is dictated by the uncertainties in dosimetry. Hence the focus of BNCT planning is the determination of dose distribution throughout normal tissue volumes. Although precise geometric manipulation of the epithermal neutron beam is not achievable, the following variables play an important role in BNCT optimization: patient orientation, dose fractionation, number of fields, megawatt-minutes per fraction, use of surface bolus, and use of collimation. Other variables which are not as easily adjustable and would not, therefore, be part of treatment planning optimization, include external patient contour, internal patient heterogeneities, boron compound distributions, and RBE's. The boron neutron capture therapy planning system developed at SUNY Stony Brook (SBNCT-Plan) was designed as an interactive graphic tool to assist the radiation oncologist in generating the optimum plan for a neutron capture treatment

  1. Development and validation of a septoplasty training model using 3-dimensional printing technology.

    AlReefi, Mahmoud A; Nguyen, Lily H P; Mongeau, Luc G; Haq, Bassam Ul; Boyanapalli, Siddharth; Hafeez, Nauman; Cegarra-Escolano, Francois; Tewfik, Marc A

    2017-04-01

    Providing alternative training modalities may improve trainees' ability to perform septoplasty. Three-dimensional printing has been shown to be a powerful tool in surgical training. The objectives of this study were to explain the development of our 3-dimensional (3D) printed septoplasty training model, to assess its face and content validity, and to present evidence supporting its ability to distinguish between levels of surgical proficiency. Imaging data of a patient with a nasal septal deviation was selected for printing. Printing materials reproducing the mechanical properties of human tissues were selected based on literature review and prototype testing. Eight expert rhinologists, 6 senior residents, and 6 junior residents performed endoscopic septoplasties on the model and completed a postsimulation survey. Performance metrics in quality (final product analysis), efficiency (time), and safety (eg, perforation length, nares damage) were recorded and analyzed in a study-blind manner. The model was judged to be anatomically correct and the steps performed realistic, with scores of 4.05 ± 0.82 and 4.2 ± 1, respectively, on a 5-point Likert scale. Ninety-two percent of residents desired the simulator to be integrated into their teaching curriculum. There was a significant difference (p simulator training models for septoplasty. Our model incorporates 2 different materials mixed into the 3 relevant consistencies necessary to simulate septoplasty. Our findings provide evidence supporting the validity of the model. © 2016 ARS-AAOA, LLC.

  2. Diagnosis of 3-dimensional geometry and stress corrosion cracking in steam generator tubes

    Lee, D.H.; Choi, M.S.; Hur, D.H.; Kim, K.M.; Han, J.H.; Song, M.H.

    2015-01-01

    Most of the corrosive degradations in steam generator tubes of nuclear power plants are closely related to the residual stress existing in the local region of a geometric change, that is, an expansion transition, u-bend, dent, bulge, etc. Therefore, accurate information on a geometric anomaly (precursor of degradation) in a tube is a prerequisite to the activity of pre- and in-service non destructive inspection for a precise and earlier detection of a defect in order to prevent a failure during an operation, and also for a root cause analysis of a failure. In this paper, a new diagnostic eddy current probe technology which has simultaneous dual function of a 3-dimensional geometry measurement and defect detection in steam generator tube is introduced. The D-Probe is a rotary type eddy current coil probe equipped with 3 different eddy current coil units (surface riding type plus-point and pancake coils for defect detection, and non-surface riding type shielded high frequency pancake coil for tube profile measurement). A specific data analysis software has been developed. By comparing the eddy current data from the defect with those from the geometric changes, the relationship between the degradation and geometric changes can be revealed. Also, it supplies information on tube location at which defect is most probable and thus, a more efficient detection of earlier degradation. The use of D-probe and analysis software has been demonstrated for steam generator tubes with various geometric anomalies in manufacturing and operating nuclear power plants

  3. Guided Autotransplantation of Teeth: A Novel Method Using Virtually Planned 3-dimensional Templates.

    Strbac, Georg D; Schnappauf, Albrecht; Giannis, Katharina; Bertl, Michael H; Moritz, Andreas; Ulm, Christian

    2016-12-01

    The aim of this study was to introduce an innovative method for autotransplantation of teeth using 3-dimensional (3D) surgical templates for guided osteotomy preparation and donor tooth placement. This report describes autotransplantation of immature premolars as treatment of an 11-year-old boy having suffered severe trauma with avulsion of permanent maxillary incisors. This approach uses modified methods from guided implant surgery by superimposition of Digital Imaging and Communications in Medicine files and 3D data sets of the jaws in order to predesign 3D printed templates with the aid of a fully digital workflow. The intervention in this complex case could successfully be accomplished by performing preplanned virtual transplantations with guided osteotomies to prevent bone loss and ensure accurate donor teeth placement in new recipient sites. Functional and esthetic restoration could be achieved by modifying methods used in guided implant surgery and prosthodontic rehabilitation. The 1-year follow-up showed vital natural teeth with physiological clinical and radiologic parameters. This innovative approach uses the latest diagnostic methods and techniques of guided implant surgery, enabling the planning and production of 3D printed surgical templates. These accurate virtually predesigned surgical templates could facilitate autotransplantation in the future by full implementation of recommended guidelines, ensuring an atraumatic surgical protocol. Copyright © 2016 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

  4. Full 3-dimensional digital workflow for multicomponent dental appliances: A proof of concept.

    van der Meer, W Joerd; Vissink, Arjan; Ren, Yijin

    2016-04-01

    The authors used a 3-dimensional (3D) printer and a bending robot to produce a multicomponent dental appliance to assess whether 3D digital models of the dentition are applicable for a full digital workflow. The authors scanned a volunteer's dentition with an intraoral scanner (Lava Chairside Oral Scanner C.O.S., 3M). A digital impression was used to design 2 multicomponent orthodontic appliances. Biocompatible acrylic baseplates were produced with the aid of a 3D printer. The metal springs and clasps were produced by a bending robot. The fit of the 2 appliances was assessed by 2 experienced orthodontists. The authors assessed both orthodontic appliances with the volunteer's dentition and found the fit to be excellent. Clinicians can fully produce a multicomponent dental appliance consisting of both an acrylic baseplate and other parts, such as clasps, springs, or screws, using a digital workflow process without the need for a physical model of the patient's dentition. Plaster models can be superfluous for orthodontic treatment as digital models can be used in all phases of a full digital workflow in orthodontics. The arduous task of making a multicomponent dental appliance that involves bending wires can possibly be replaced by a computer, design software, a 3D printer, and a bending robot. Copyright © 2016 American Dental Association. Published by Elsevier Inc. All rights reserved.

  5. 3-Dimensional Modeling of Capacitively and Inductively Coupled Plasma Etching Systems

    Rauf, Shahid

    2008-10-01

    Low temperature plasmas are widely used for thin film etching during micro and nano-electronic device fabrication. Fluid and hybrid plasma models were developed 15-20 years ago to understand the fundamentals of these plasmas and plasma etching. These models have significantly evolved since then, and are now a major tool used for new plasma hardware design and problem resolution. Plasma etching is a complex physical phenomenon, where inter-coupled plasma, electromagnetic, fluid dynamics, and thermal effects all have a major influence. The next frontier in the evolution of fluid-based plasma models is where these models are able to self-consistently treat the inter-coupling of plasma physics with fluid dynamics, electromagnetics, heat transfer and magnetostatics. We describe one such model in this paper and illustrate its use in solving engineering problems of interest for next generation plasma etcher design. Our 3-dimensional plasma model includes the full set of Maxwell equations, transport equations for all charged and neutral species in the plasma, the Navier-Stokes equation for fluid flow, and Kirchhoff's equations for the lumped external circuit. This model also includes Monte Carlo based kinetic models for secondary electrons and stochastic heating, and can take account of plasma chemistry. This modeling formalism allows us to self-consistently treat the dynamics in commercial inductively and capacitively coupled plasma etching reactors with realistic plasma chemistries, magnetic fields, and reactor geometries. We are also able to investigate the influence of the distributed electromagnetic circuit at very high frequencies (VHF) on the plasma dynamics. The model is used to assess the impact of azimuthal asymmetries in plasma reactor design (e.g., off-center pump, 3D magnetic field, slit valve, flow restrictor) on plasma characteristics at frequencies from 2 -- 180 MHz. With Jason Kenney, Ankur Agarwal, Ajit Balakrishna, Kallol Bera, and Ken Collins.

  6. SU-E-T-104: Development of 3 Dimensional Dosimetry System for Gamma Knife

    Yoon, K; Kwak, J; Cho, B; Lee, D; Ahn, S [Asan Medical Center, Seoul (Korea, Republic of)

    2014-06-01

    Purpose: The aim of this study was to develop a new 3 dimensional dosimetry system to verify the dosimetric accuracy of Leksell Gamma Knife-Perfexion™ (LGK) (Elekta, Norcross, GA). Methods: We designed and manufactured a lightweight dosimetry instrument to be equipped with the head frame to LGK. It consists of a head phantom, a scintillator, a CCD camera and a step motor. The 10×10 cm2 sheet of Gd2O3;Tb phosphor or Gafchromic EBT3 film was located at the center of the 16 cm diameter hemispherical PMMA, the head phantom. The additional backscatter compensating material of 1 cm thick PMMA plate was placed downstream of the phosphor sheet. The backscatter plate was transparent for scintillation lights to reach the CCD camera with 1200×1200 pixels by 5.2 um pitch. With This equipment, 300 images with 0.2 mm of slice gap were acquired under three collimator setups (4mm, 8mm and 16mm), respectively. The 2D projected doses from 3D distributions were compared with the exposured film dose. Results: As all doses normalized by the maximum dose value in 16 mm setup, the relative differences between the equipment dose and film dose were 0.2% for 4mm collimator and 0.5% for 8mm. The acquisition of 300 images by the equipment took less than 3 minutes. Conclusion: The new equipment was verified to be a good substitute to radiochromic film, with which required more time and resources. Especially, the new methods was considered to provide much convenient and faster solution in the 3D dose acquisition for LGK.

  7. Using a clinical protocol for orthognathic surgery and assessing a 3-dimensional virtual approach: current therapy.

    Quevedo, Luis A; Ruiz, Jessica V; Quevedo, Cristobal A

    2011-03-01

    Oral and maxillofacial surgeons who perform orthognathic surgery face major changes in their practices, and these challenges will increase in the near future, because the extraordinary advances in technology applied to our profession are not only amazing but are becoming the standard of care as they promote improved outcomes for our patients. Orthognathic surgery is one of the favorite areas of practicing within the scope of practice of an oral and maxillofacial surgeon. Our own practice in orthognathic surgery has completed over 1,000 surgeries of this type. Success is directly related to the consistency and capability of the surgical-orthodontic team to achieve predictable, stable results, and our hypothesis is that a successful result is directly related to the way we take our records and perform diagnosis and treatment planning following basic general principles. Now that we have the opportunity to plan and treat 3-dimensional (3D) problems with 3D technology, we should enter into this new era with appropriate standards to ensure better results, instead of simply enjoying these new tools, which will clearly show not only us but everyone what we do when we perform orthognathic surgery. Appropriate principles need to be taken into account when implementing this new technology. In other words, new technology is welcome, but we do not have to reinvent the wheel. The purpose of this article is to review the current protocol that we use for orthognathic surgery and compare it with published protocols that incorporate new 3D and virtual technology. This report also describes our approach to this new technology. Copyright © 2011 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

  8. Predictors of Hypothyroidism in Hodgkin Lymphoma Survivors After Intensity Modulated Versus 3-Dimensional Radiation Therapy.

    Pinnix, Chelsea C; Cella, Laura; Andraos, Therese Y; Ayoub, Zeina; Milgrom, Sarah A; Gunther, Jillian; Thosani, Sonali; Wogan, Christine; Conson, Manuel; D'Avino, Vittoria; Oki, Yasuhiro; Fanale, Michelle; Lee, Hun J; Neelapu, Sattva; Fayad, Luis; Hagemeister, Frederick; Rodriguez, M Alma; Nastoupil, Loretta J; Nieto, Yago; Qiao, Wei; Pacelli, Roberto; Dabaja, Bouthaina

    2018-03-14

    To identify predictors of hypothyroidism after chemoradiation therapy for Hodgkin lymphoma (HL) and to compare outcomes after intensity modulated radiation therapy (IMRT) with those after 3-dimensional (3D) conformal radiation therapy (CRT). Ninety patients who underwent involved-site IMRT in 2009 through 2014 were evaluated for treatment-induced hypothyroidism, defined as elevated thyroid-stimulating hormone or decreased free thyroxine levels (or both). Receiver operating characteristic curve analysis identified individuals at low versus high risk based on dosimetric variables. Dosimetric cutoff points were verified with an external data set of 50 patients who underwent 3D-CRT. In the IMRT group, most patients (75 [83%]) had stage II HL, and the median prescribed dose was 30.6 Gy; in the 3D-CRT group, 32 patients (64%) had stage II HL, and the median prescribed dose was 32.0 Gy. No differences were found in the proportions of patients with bilateral (P = .982) or unilateral (P = .074) neck involvement between the 2 groups. Hypothyroidism rates were marginally higher in the IMRT group, with estimated 3-year rates of freedom from hypothyroidism of 56.1% in the 3D-CRT group and 40% in the IMRT group (P = .057). Univariate analysis showed that smaller thyroid volume and higher thyroid dose were associated with hypothyroidism in both groups (P hypothyroidism (P = .001 and P hypothyroidism (P hypothyroidism after either IMRT or 3D-CRT for HL. IMRT may confer a higher risk than 3D-CRT unless a treatment avoidance structure is used during planning. Copyright © 2018 Elsevier Inc. All rights reserved.

  9. Evaluation of xerostomia following 3 dimensional conformal radiotherapy for nasopharyngeal cancer patients

    Park, Young Je; Ahn, Yong Chan; Park, Won; Ju, Sang Gyu; Nam, Hee Rim; Oh, Dong Ryul; Park, Hee Chul

    2006-01-01

    This study is to evaluate the xerostomia following 3-dimensional conformal radiation therapy (3D CRT) in nasopharynx cancer patients using the xerostomia questionnaire score (XQS). Questionnaire study was done on 51 patients with nasopharynx cancer who received 3D CRT from Dec. 2000 to Aug. 2005. 3D CRT technique is based on 'serial shrinking field' concept by 3 times of computed tomography (CT) simulation. Total target dose to the primary tumor was 72 Gy with 1.8 Gy daily fractions. Xerostomia was assessed with 4-questions XQS, and the associations between XQS and time elapsed after RT, age, sex, stage, concurrent chemotherapy, an parotid dose were analyzed. Concurrent chemotherapy was given to 40 patients and RT alone was given to 11 patients. The median time elapsed after 3D CRT was 20 (1 ∼ 58) months and the mean XQS of all 51 patients was 8.4 ± 1.9 (6 ∼ 14). XQS continuously and significantly decreased over time after 3D CRT (χ 2 -0.484, ρ < 0.05). There was no significant difference in XQS according to sex, age, and stag. However, XQS of concurrent chemotherapy patients was significantly higher than RT alone patients (ρ = 0.001). XQS of patients receiving total mean parotid dose ≥ 35 Gy was significantly higher than < 35 Gy (ρ = 0.05). Decreasing tendency of XQS over time after 3D CRT was observed. Concurrent chemotherapy and total mean parotid dose ≥ 35 Gy were suggested to adversely affect radiation-induced xerostomia

  10. Renal calyceal anatomy characterization with 3-dimensional in vivo computerized tomography imaging.

    Miller, Joe; Durack, Jeremy C; Sorensen, Mathew D; Wang, James H; Stoller, Marshall L

    2013-02-01

    Calyceal selection for percutaneous renal access is critical for safe, effective performance of percutaneous nephrolithotomy. Available anatomical evidence is contradictory and incomplete. We present detailed renal calyceal anatomy obtained from in vivo 3-dimentional computerized tomography renderings. A total of 60 computerized tomography urograms were randomly selected. The renal collecting system was isolated and 3-dimensional renderings were constructed. The primary plane of each calyceal group of 100 kidneys was determined. A coronal maximum intensity projection was used for simulated percutaneous access. The most inferior calyx was designated calyx 1. Moving superiorly, the subsequent calyces were designated calyx 2 and, when present, calyx 3. The surface rendering was rotated to assess the primary plane of the calyceal group and the orientation of the select calyx. The primary plane of the upper pole calyceal group was mediolateral in 95% of kidneys and the primary plane of the lower pole calyceal group was anteroposterior in 95%. Calyx 2 was chosen in 90 of 97 simulations and it was appropriate in 92%. Calyx 3 was chosen in 7 simulations but it was appropriate in only 57%. Calyx 1 was not selected in any simulation and it was anteriorly oriented in 75% of kidneys. Appropriate lower pole calyceal access can be reliably accomplished with an understanding of the anatomical relationship between individual calyceal orientation and the primary plane of the calyceal group. Calyx 2 is most often appropriate for accessing the anteroposterior primary plane of the lower pole. Calyx 1 is most commonly oriented anterior. Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  11. A customized bolus produced using a 3-dimensional printer for radiotherapy.

    Shin-Wook Kim

    Full Text Available OBJECTIVE: Boluses are used in high-energy radiotherapy in order to overcome the skin sparing effect. In practice though, commonly used flat boluses fail to make a perfect contact with the irregular surface of the patient's skin, resulting in air gaps. Hence, we fabricated a customized bolus using a 3-dimensional (3D printer and evaluated its feasibility for radiotherapy. METHODS: We designed two kinds of bolus for production on a 3D printer, one of which was the 3D printed flat bolus for the Blue water phantom and the other was a 3D printed customized bolus for the RANDO phantom. The 3D printed flat bolus was fabricated to verify its physical quality. The resulting 3D printed flat bolus was evaluated by assessing dosimetric parameters such as D1.5 cm, D5 cm, and D10 cm. The 3D printed customized bolus was then fabricated, and its quality and clinical feasibility were evaluated by visual inspection and by assessing dosimetric parameters such as Dmax, Dmin, Dmean, D90%, and V90%. RESULTS: The dosimetric parameters of the resulting 3D printed flat bolus showed that it was a useful dose escalating material, equivalent to a commercially available flat bolus. Analysis of the dosimetric parameters of the 3D printed customized bolus demonstrated that it is provided good dose escalation and good contact with the irregular surface of the RANDO phantom. CONCLUSIONS: A customized bolus produced using a 3D printer could potentially replace commercially available flat boluses.

  12. The Interobserver Variability and Diagnostic Performance of 3-Dimensional Breast Ultrasound

    Lyou, Chae Yeon; Kim, Sun Mi; Jang, Mi Jung; Kim, Sung Won; Kang, Eun Young; Park, So Yeon; Moon, Woo Kyung

    2011-01-01

    We wanted to evaluate the interobserver variability and diagnostic performance of 3-dimensional (3D) breast ultrasound (US) as compared with that of 2- dimensional (2D) US. We included 150 patients who received US-guided core biopsy and 3D US between June 2009 and April 2010. Three breast imaging radiologists analyzed the 2D and 3D US images using the Breast Imaging Reporting and Data System (BI-RADS) lexicon. The intra-observer agreement and inter-observer agreement were calculated. The sensitivity and specificity of 2D and 3D US were evaluated. The intra-observer agreement between 2D and 3D US was mostly slight or fair agreement. However, in terms of the final category, there was substantial agreement for all three radiologists. The inter-observer agreement of 3D US was similar to that of 2D US (moderate agreement for shape, orientation, circumscribed margin and boundary: fair agreement for indistinct margin, angular margin, microlobulated margin, echo pattern and final category). The sensitivity of 3D US for breast cancer was higher than that of 2D US for two radiologists (2D vs. 3D for reader 2: 55.8% vs. 61.5%, 2D vs. 3D for reader 3: 59.6% vs. 63.5%), and the specificity of 3D US was lower than that of 2D US for all the readers (2D vs. 3D for reader 1: 90.8% vs. 86.7%, 2D vs. 3D for reader 2: 90.8% vs. 87.8%, 2D vs. 3D for reader 3: 94.9% vs. 90.8%), but the difference was not significant (p ≥ 0.05). The interobserver variability and diagnostic performance of 3D breast US were similar to those of 2D US

  13. Extensions of the 3-dimensional plasma transport code E3D

    Runov, A.; Schneider, R.; Kasilov, S.; Reiter, D.

    2004-01-01

    One important aspect of modern fusion research is plasma edge physics. Fluid transport codes extending beyond the standard 2-D code packages like B2-Eirene or UEDGE are under development. A 3-dimensional plasma fluid code, E3D, based upon the Multiple Coordinate System Approach and a Monte Carlo integration procedure has been developed for general magnetic configurations including ergodic regions. These local magnetic coordinates lead to a full metric tensor which accurately accounts for all transport terms in the equations. Here, we discuss new computational aspects of the realization of the algorithm. The main limitation to the Monte Carlo code efficiency comes from the restriction on the parallel jump of advancing test particles which must be small compared to the gradient length of the diffusion coefficient. In our problems, the parallel diffusion coefficient depends on both plasma and magnetic field parameters. Usually, the second dependence is much more critical. In order to allow long parallel jumps, this dependence can be eliminated in two steps: first, the longitudinal coordinate x 3 of local magnetic coordinates is modified in such a way that in the new coordinate system the metric determinant and contra-variant components of the magnetic field scale along the magnetic field with powers of the magnetic field module (like in Boozer flux coordinates). Second, specific weights of the test particles are introduced. As a result of increased parallel jump length, the efficiency of the code is about two orders of magnitude better. (copyright 2004 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim) (orig.)

  14. Choroidal thinning in diabetes type 1 detected by 3-dimensional 1060 nm optical coherence tomography.

    Esmaeelpour, Marieh; Brunner, Simon; Ansari-Shahrezaei, Siamak; Shahrezaei, Siamak Ansari; Nemetz, Susanne; Povazay, Boris; Kajic, Vedran; Drexler, Wolfgang; Binder, Susanne

    2012-10-03

    To map choroidal (ChT) and retinal thickness (RT) in patients with diabetes type 1 with and without maculopathy and retinopathy in order to compare them with healthy subjects using high speed 3-dimensional (3D) 1060 nm optical coherence tomography (OCT). Thirty-three eyes from 33 diabetes type 1 subjects (23-57 years, 15 male) divided into groups of without pathology (NDR) and with pathology (DR; including microaneurysms, exudates, clinically significant macular-oedema and proliferative retinopathy) were compared with 20 healthy axial eye length and age-matched subjects (24-57 years, 9 male), imaged by high speed (60.000 A-scans/s) 3D 1060 nm OCT performed over 36° × 36° field of view. Ocular health status, disease duration, body mass index, haemoglobin-A1c, and blood pressure (bp) measurements were recorded. Subfoveal ChT, and 2D topographic maps between retinal pigment epithelium and the choroidal/scleral-interface, were automatically generated and statistically analyzed. Subfoveal ChT (mean ± SD, μm) for healthy eyes was 388 ± 109; significantly thicker than all diabetic groups, 291 ± 64 for NDR, and 303 ± 82 for DR (ANOVA P 0.05). Compared with healthy eyes and the NDR, the averaged DR ChT-map demonstrated temporal thinning that extended superiorly and temporal-inferiorly (unpaired t-test, P 0.05). ChT is decreased in diabetes type 1, independent of the absence of pathology and of diabetic disease duration. In eyes with pathology, 3D 1060 nm OCT averaged maps showed an extension of the thinning area matching retinal lesions and suggesting its involvement on onset or progression of disease.

  15. Reproducibility of a 3-dimensional gyroscope in measuring shoulder anteflexion and abduction

    Penning Ludo I F

    2012-07-01

    Full Text Available Abstract Background Few studies have investigated the use of a 3-dimensional gyroscope for measuring the range of motion (ROM in the impaired shoulder. Reproducibility of digital inclinometer and visual estimation is poor. This study aims to investigate the reproducibility of a tri axial gyroscope in measurement of anteflexion, abduction and related rotations in the impaired shoulder. Methods Fifty-eight patients with either subacromial impingement (27 or osteoarthritis of the shoulder (31 participated. Active anteflexion, abduction and related rotations were measured with a tri axial gyroscope according to a test retest protocol. Severity of shoulder impairment and patient perceived pain were assessed by the Disability of Arm Shoulder and Hand score (DASH and the Visual Analogue Scale (VAS. VAS scores were recorded before and after testing. Results In two out of three hospitals patients with osteoarthritis (n = 31 were measured, in the third hospital patients with subacromial impingement (n = 27. There were significant differences among hospitals for the VAS and DASH scores measured before and after testing. The mean differences between the test and retest means for anteflexion were −6 degrees (affected side, 9 (contralateral side and for abduction 15 degrees (affected side and 10 degrees (contralateral side. Bland & Altman plots showed that the confidence intervals for the mean differences fall within −6 up to 15 degrees, individual test - retest differences could exceed these limits. A simulation according to ‘Generalizability Theory’ produces very good coefficients for anteflexion and related rotation as a comprehensive measure of reproducibility. Optimal reproducibility is achieved with 2 repetitions for anteflexion. Conclusions Measurements were influenced by patient perceived pain. Differences in VAS and DASH might be explained by different underlying pathology. These differences in shoulder pathology however did not alter

  16. Osseous Anatomy of the Distal Radioulnar Joint: An Assessment Using 3-Dimensional Modeling and Clinical Implications.

    Daneshvar, Parham; Willing, Ryan; Pahuta, Markian; Grewal, Ruby; King, Graham J W

    2016-11-01

    Using a novel technique, we assess and describe the distal radioulnar joint (DRUJ) anatomy. The purpose of this study was to provide the anatomic dimensions of the DRUJ and to evaluate contralateral symmetry. Computed tomography images of 100 cadaveric forearms were obtained. Three-dimensional models of the radius and ulna were generated and evaluated using 3-dimensional modeling software. Measurements of the radius of curvature of the sigmoid notch (SN) and ulnar head (UH), as well as the length of the SN and volar and dorsal lips were performed in the axial and coronal sequences. In addition, mid-coronal angular measurements were made of the SN and UH to quantify the obliquity of the DRUJ. All coronal measurements were performed with the forearm set to neutral rotation. The average ulnar variance was -0.9 ± 1.8 mm. The radius of curvature of the UH (8.2 ± 1.3 mm) was markedly smaller than that of the SN (18.2 ± 8.5 mm). The length of the SN in coronal sequences increased from volar to dorsal by 65%. The mid-coronal angle (DRUJ obliquity) of the SN and UH measured 6.0 ± 9.9° and 18.0 ± 9.9°, respectively. A direct inverse correlation was demonstrated in the obliquity of the DRUJ and ulnar variance. All anatomic measurements were similar when comparing bilateral specimens. The SN length tends to increase in size from volar to dorsal. Bilateral specimens from the same individual demonstrate similarities and can be cautiously used for comparison. The relationships and measurements demonstrated in this study can be a guide when considering reconstructive procedures or dealing with complex fractures involving the DRUJ. Copyright © 2016 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.

  17. Novel Radiobiological Gamma Index for Evaluation of 3-Dimensional Predicted Dose Distribution

    Sumida, Iori, E-mail: sumida@radonc.med.osaka-u.ac.jp [Department of Radiation Oncology, Osaka University Graduate School of Medicine, Osaka (Japan); Yamaguchi, Hajime; Kizaki, Hisao; Aboshi, Keiko; Tsujii, Mari; Yoshikawa, Nobuhiko; Yamada, Yuji [Department of Radiation Oncology, NTT West Osaka Hospital, Osaka (Japan); Suzuki, Osamu; Seo, Yuji [Department of Radiation Oncology, Osaka University Graduate School of Medicine, Osaka (Japan); Isohashi, Fumiaki [Department of Radiation Oncology, NTT West Osaka Hospital, Osaka (Japan); Yoshioka, Yasuo [Department of Radiation Oncology, Osaka University Graduate School of Medicine, Osaka (Japan); Ogawa, Kazuhiko [Department of Radiation Oncology, NTT West Osaka Hospital, Osaka (Japan)

    2015-07-15

    Purpose: To propose a gamma index-based dose evaluation index that integrates the radiobiological parameters of tumor control (TCP) and normal tissue complication probabilities (NTCP). Methods and Materials: Fifteen prostate and head and neck (H&N) cancer patients received intensity modulated radiation therapy. Before treatment, patient-specific quality assurance was conducted via beam-by-beam analysis, and beam-specific dose error distributions were generated. The predicted 3-dimensional (3D) dose distribution was calculated by back-projection of relative dose error distribution per beam. A 3D gamma analysis of different organs (prostate: clinical [CTV] and planned target volumes [PTV], rectum, bladder, femoral heads; H&N: gross tumor volume [GTV], CTV, spinal cord, brain stem, both parotids) was performed using predicted and planned dose distributions under 2%/2 mm tolerance and physical gamma passing rate was calculated. TCP and NTCP values were calculated for voxels with physical gamma indices (PGI) >1. We propose a new radiobiological gamma index (RGI) to quantify the radiobiological effects of TCP and NTCP and calculate radiobiological gamma passing rates. Results: The mean RGI gamma passing rates for prostate cases were significantly different compared with those of PGI (P<.03–.001). The mean RGI gamma passing rates for H&N cases (except for GTV) were significantly different compared with those of PGI (P<.001). Differences in gamma passing rates between PGI and RGI were due to dose differences between the planned and predicted dose distributions. Radiobiological gamma distribution was visualized to identify areas where the dose was radiobiologically important. Conclusions: RGI was proposed to integrate radiobiological effects into PGI. This index would assist physicians and medical physicists not only in physical evaluations of treatment delivery accuracy, but also in clinical evaluations of predicted dose distribution.

  18. New stereoacuity test using a 3-dimensional display system in children.

    Sang Beom Han

    Full Text Available The previously developed 3-dimensional (3D display stereoacuity tests were validated only at distance. We developed a new stereoacuity test using a 3D display that works both at near and distance and evaluated its validity in children with and without strabismus. Sixty children (age range, 6 to 18 years with variable ranges of stereoacuity were included. Side-by-side randot images of 4 different simple objects (star, circle, rectangle, and triangle with a wide range of crossed horizontal disparities (3000 to 20 arcsec were randomly displayed on a 3D monitor with MATLAB (Matworks, Inc., Natick, MA, USA and were presented to subjects wearing shutter glasses at 0.5 m and 3 m. The 3D image was located in front of (conventional or behind (proposed the background image on the 3D monitor. The results with the new 3D stereotest (conventional and proposed were compared with those of the near and distance Randot stereotests. At near, the Bland-Altman plots of the conventional and proposed 3D stereotest did not show significant difference, both of which were poorer than the Randot test. At distance, the results of the proposed 3D stereotest were similar to the Randot test, but the conventional 3D stereotest results were better than those of the other two tests. The results of the proposed 3D stereotest and Randot stereotest were identical in 83.3% at near and 88.3% at distance. More than 95% of subjects showed concordance within 2 grades between the 2 tests at both near and distance. In conclusion, the newly proposed 3D stereotest shows good concordance with the Randot stereotests in children with and without strabismus.

  19. Fabrication of 3-Dimensional Porous Graphene Materials for Lithium Ion Batteries

    Jiang, Yu; Jiang, Zhong-Jie; Cheng, Shuang; Liu, Meilin

    2014-01-01

    A simple two-step procedure involving hydrothermal reaction and subsequent calcination has been employed to synthesis porous graphene material, which exhibits significantly high electrochemical performance when used as the anode in lithium ion batteries. - Highlights: • A PGM been synthesized by a simple two-step process involving hydrothermal reaction and subsequent calcination. • The PGM exhibits exhibit a significantly high specific surface area. • The PGM can deliver large capacities and excellent cycling performance when used in LIBs. • The high electrochemical performance of the PGM is attributed to its unique porous structure with more disordered carbon atoms. - Abstract: A 3-dimensional porous graphene material (PGM) has been synthesized using a simple two-step process: hydrothermal reaction and calcination. Hydrothermal reaction of graphene oxide (GO) in the presence of resorcinol and glutaraldehyde leads to covalent grafting of partially reduced GO with glutaraldehyde and the deposition of phenolic resin. Subsequent calcination of the composite consisting of phenolic resin deposited on partially reduced GO in the presence of KOH produces structurally stable, highly porous graphene material with a specific surface area of ∼1,066 ± 2 m 2 g −1 . When used as an active electrode material in a lithium battery, the PGM exhibits an initial discharge capacity of ∼1,538 mAh g −1 , which is significantly higher than those of graphite and other carbonaceous materials reported previously. More importantly, when cycled at higher discharge/charge rates, the PGM-based electrodes still deliver large capacities and excellent cycling performance, demonstrating great potential for high-performance lithium-ion batteries. The attractive electrochemical performance of the PGM is attributed to its unique porous structure with large specific surface area and the presence of more disordered carbon atoms produced by the KOH activation

  20. High-resolution, 2- and 3-dimensional imaging of uncut, unembedded tissue biopsy samples.

    Torres, Richard; Vesuna, Sam; Levene, Michael J

    2014-03-01

    Despite continuing advances in tissue processing automation, traditional embedding, cutting, and staining methods limit our ability for rapid, comprehensive visual examination. These limitations are particularly relevant to biopsies for which immediate therapeutic decisions are most necessary, faster feedback to the patient is desired, and preservation of tissue for ancillary studies is most important. The recent development of improved tissue clearing techniques has made it possible to consider use of multiphoton microscopy (MPM) tools in clinical settings, which could address difficulties of established methods. To demonstrate the potential of MPM of cleared tissue for the evaluation of unembedded and uncut pathology samples. Human prostate, liver, breast, and kidney specimens were fixed and dehydrated by using traditional histologic techniques, with or without incorporation of nucleic acid fluorescent stains into dehydration steps. A benzyl alcohol/benzyl benzoate clearing protocol was substituted for xylene. Multiphoton microscopy was performed on a home-built system. Excellent morphologic detail was achievable with MPM at depths greater than 500 μm. Pseudocoloring produced images analogous to hematoxylin-eosin-stained images. Concurrent second-harmonic generation detection allowed mapping of collagen. Subsequent traditional section staining with hematoxylin-eosin did not reveal any detrimental morphologic effects. Sample immunostains on renal tissue showed preservation of normal reactivity. Complete reconstructions of 1-mm cubic samples elucidated 3-dimensional architectural organization. Multiphoton microscopy on cleared, unembedded, uncut biopsy specimens shows potential as a practical clinical tool with significant advantages over traditional histology while maintaining compatibility with gold standard techniques. Further investigation to address remaining implementation barriers is warranted.

  1. Transabdominal ultrasonography, computed tomography and electronic portal imaging for 3-dimensional conformal radiotherapy for prostate cancer

    Jereczek-Fossa, B.A.; Orecchia, R.; Cattani, F.; Garibaldi, C.; Cambria, R.; Valenti, M.; Ciocca, M.; Zerini, D.; Boboc, G.I.; Vavassori, A.; Ivaldi, G.B.; Kowalczyk, A.; Matei, D.V.; Cobelli, O. de

    2007-01-01

    Purpose: To evaluate the feasibility and accuracy of daily B-mode acquisition and targeting ultrasound-based prostate localization (BAT trademark) and to compare it with computed tomography (CT) and electronic portal imaging (EPI) in 3-dimensional conformal radiotherapy (3-D CRT) for prostate cancer. Patients and Methods: Ten patients were treated with 3-D CRT (72 Gy/30 fractions, 2.4 Gy/fraction, equivalent to 80 Gy/40 fractions, for α/β ratio of 1.5 Gy) and daily BAT-based prostate localization. For the first 5 fractions, CT and EPI were also performed in order to compare organ-motion and set-up error, respectively. Results: 287 BAT-, 50 CT- and 46 EPI-alignments were performed. The average BAT-determined misalignments in latero-lateral, antero-posterior and cranio-caudal directions were -0.9 mm ± 3.3 mm, 1.0 mm ± 4.0 mm and -0.9 mm ± 3.8 mm, respectively. The differences between BAT- and CT-determined organ-motion in latero-lateral, antero-posterior and cranio-caudal directions were 2.7 mm ± 1.9 mm, 3.9 ± 2.8 mm and 3.4 ± 3.0 mm, respectively. Weak correlation was found between BAT- and CT-determined misalignments in antero-posterior direction, while no correlation was observed in latero-lateral and cranio-caudal directions. The correlation was more significant when only data of good image-quality patients were analyzed (8 patients). Conclusion: BAT ensures the relative positions of target are the same during treatment and in treatment plan, however, the reliability of alignment is patient-dependent. The average BAT-determined misalignments were small, confirming the prevalence of random errors in 3-D CRT. Further study is warranted in order to establish the clinical value of BAT. (orig.)

  2. Treatment of severe porcine tracheomalacia with a 3-dimensionally printed, bioresorbable, external airway splint

    Zopf, David A.; Flanagan, Colleen L.; Wheeler, Matthew; Hollister, Scott J.; Green, Glenn E.

    2015-01-01

    Importance The study demonstrates an application for 3-dimensional (3D) printing that may serve as an effective intervention for severe tracheobronchomalacia. Objective A novel 3D printed, bioresorbable airway splint is tested for efficacy in extending survival in an animal model of severe, life-threatening tracheobronchomalacia. Participants Evaluation of an external airway splint for severe, life-threatening tracheobronchomalacia in a porcine animal model. Setting Multi-institutional and multidisciplinary collaboration between biomedical engineering laboratories and an academic animal surgery center. Interventions Experimental analysis of a 3D printed, bioresorbable airway splint is assessed in a porcine animal model of life-threatening tracheobronchomalacia. The open-cylindrical, bellow shaped porous polycaprolactone splint is placed externally and designed to suspend the underlying collapsed airway. Control animals (n=3) undergoing tracheal cartilage division and inner tracheal lumen dissociation and experimental animals (n=3) receiving the same model with overlying placement of the newly developed airway splint were evaluated. Main Outcomes and Measures An animal model for severe, life-threatening tracheobronchomalacia is proposed. Complete or near complete tracheal lumen collapse was observed in each animal with resolution of symptoms in all of the experimental animals after splint placement. Using our severe tracheobronchomalacia animal model, survival was significantly longer in duration in the experimental group receiving the airway splint after model creation when compared to model creation alone (p = 0.0495). Mortality in the experimental group was related to infection. Conclusions A multidisciplinary effort producing a CAD/CAM, bioresorbable tracheobronchial splint was tested in a porcine model of severe tracheomalacia and was found to extend survival. PMID:24232078

  3. The Reliability of a Novel Mobile 3-dimensional Wound Measurement Device.

    Anghel, Ersilia L; Kumar, Anagha; Bigham, Thomas E; Maselli, Kathryn M; Steinberg, John S; Evans, Karen K; Kim, Paul J; Attinger, Christopher E

    2016-11-01

    Objective assessment of wound dimensions is essential for tracking progression and determining treatment effectiveness. A reliability study was designed to establish intrarater and interrater reliability of a novel mobile 3-dimensional wound measurement (3DWM) device. Forty-five wounds were assessed by 2 raters using a 3DWM device to obtain length, width, area, depth, and volume measurements. Wounds were also measured manually, using a disposable ruler and digital planimetry. The intraclass correlation coefficient (ICC) was used to establish intrarater and interrater reliability. High levels of intrarater and interrater agreement were observed for area, length, and width; ICC = 0.998, 0.977, 0.955 and 0.999, 0.997, 0.995, respectively. Moderate levels of intrarater (ICC = 0.888) and interrater (ICC = 0.696) agreement were observed for volume. Lastly, depth yielded an intrarater ICC of 0.360 and an interrater ICC of 0.649. Measures from the 3DWM device were highly correlated with those obtained from scaled photography for length, width, and area (ρ = 0.997, 0.988, 0.997, P device yielded correlations of ρ = 0.990, 0.987, 0.996 with P device was found to be highly reliable for measuring wound areas for a range of wound sizes and types as compared to manual measurement and digital planimetry. The depth and therefore volume measurement using the 3DWM device was found to have a lower ICC, but volume ICC alone was moderate. Overall, this device offers a mobile option for objective wound measurement in the clinical setting.

  4. Estimating the costs of intensity-modulated and 3-dimensional conformal radiotherapy in Ontario.

    Yong, J H E; McGowan, T; Redmond-Misner, R; Beca, J; Warde, P; Gutierrez, E; Hoch, J S

    2016-06-01

    Radiotherapy is a common treatment for many cancers, but up-to-date estimates of the costs of radiotherapy are lacking. In the present study, we estimated the unit costs of intensity-modulated radiotherapy (imrt) and 3-dimensional conformal radiotherapy (3D-crt) in Ontario. An activity-based costing model was developed to estimate the costs of imrt and 3D-crt in prostate cancer. It included the costs of equipment, staff, and supporting infrastructure. The framework was subsequently adapted to estimate the costs of radiotherapy in breast cancer and head-and-neck cancer. We also tested various scenarios by varying the program maturity and the use of volumetric modulated arc therapy (vmat) alongside imrt. From the perspective of the health care system, treating prostate cancer with imrt and 3D-crt respectively cost $12,834 and $12,453 per patient. The cost of radiotherapy ranged from $5,270 to $14,155 and was sensitive to analytic perspective, radiation technique, and disease site. Cases of head-and-neck cancer were the most costly, being driven by treatment complexity and fractions per treatment. Although imrt was more costly than 3D-crt, its cost will likely decline over time as programs mature and vmat is incorporated. Our costing model can be modified to estimate the costs of 3D-crt and imrt for various disease sites and settings. The results demonstrate the important role of capital costs in studies of radiotherapy cost from a health system perspective, which our model can accommodate. In addition, our study established the need for future analyses of imrt cost to consider how vmat affects time consumption.

  5. Realization of masticatory movement by 3-dimensional simulation of the temporomandibular joint and the masticatory muscles.

    Park, Jong-Tae; Lee, Jae-Gi; Won, Sung-Yoon; Lee, Sang-Hee; Cha, Jung-Yul; Kim, Hee-Jin

    2013-07-01

    Masticatory muscles are closely involved in mastication, pronunciation, and swallowing, and it is therefore important to study the specific functions and dynamics of the mandibular and masticatory muscles. However, the shortness of muscle fibers and the diversity of movement directions make it difficult to study and simplify the dynamics of mastication. The purpose of this study was to use 3-dimensional (3D) simulation to observe the functions and movements of each of the masticatory muscles and the mandible while chewing. To simulate the masticatory movement, computed tomographic images were taken from a single Korean volunteer (30-year-old man), and skull image data were reconstructed in 3D (Mimics; Materialise, Leuven, Belgium). The 3D-reconstructed masticatory muscles were then attached to the 3D skull model. The masticatory movements were animated using Maya (Autodesk, San Rafael, CA) based on the mandibular motion path. During unilateral chewing, the mandible was found to move laterally toward the functional side by contracting the contralateral lateral pterygoid and ipsilateral temporalis muscles. During the initial mouth opening, only hinge movement was observed at the temporomandibular joint. During this period, the entire mandible rotated approximately 13 degrees toward the bicondylar horizontal plane. Continued movement of the mandible to full mouth opening occurred simultaneously with sliding and hinge movements, and the mandible rotated approximately 17 degrees toward the center of the mandibular ramus. The described approach can yield data for use in face animation and other simulation systems and for elucidating the functional components related to contraction and relaxation of muscles during mastication.

  6. Comparison of the Osteogenic Potential of Mineral Trioxide Aggregate and Endosequence Root Repair Material in a 3-dimensional Culture System.

    Rifaey, Hisham S; Villa, Max; Zhu, Qiang; Wang, Yu-Hsiung; Safavi, Kamran; Chen, I-Ping

    2016-05-01

    The ability to promote osteoblast differentiation is a desirable property of root-end filling materials. Several in vitro studies compare the cytotoxicity and physical properties between mineral trioxide aggregate (MTA) and Endosequence root repair material (ERRM), but not their osteogenic potential. Three-dimensional cultures allow cells to better maintain their physiological morphology and better resemble in vivo cellular response than 2-dimensional cultures. Here we examined the osteogenic potential of MTA and ERRM by using a commercially available 3-dimensional Alvetex scaffold. Mandibular osteoblasts were derived from 3-week-old male transgenic reporter mice where mature osteoblasts express green fluorescent protein (GFP) driven by a 2.3-kilobase type I collagen promoter (Col(I)-2.3). Mandibular osteoblasts were grown on Alvetex in direct contact with MTA, ERRM, or no material (negative control) for 14 days. Osteoblast differentiation was evaluated by expression levels of osteogenic genes by using quantitative polymerase chain reaction and by the spatial dynamics of Col(I)-2.3 GFP-positive mature osteoblasts within the Alvetex scaffolds by using 2-photon microscopy. ERRM significantly increased alkaline phosphatase (Alp) and bone sialoprotein (Bsp) expression compared with MTA and negative control groups. Both MTA and ERRM increased osterix (Osx) mRNA significantly compared with the negative control group. The percentage of Col(I)-2.3 GFP-positive cells over total cells within Alvetex was the highest in the ERRM group, followed by MTA and by negative controls. ERRM promotes osteoblast differentiation better than MTA and controls with no material in a 3-dimensional culture system. Alvetex scaffolds can be used to test endodontic materials. Copyright © 2016 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

  7. Licochalcone A exerts antitumor activity in bladder cancer cell lines ...

    Wangjing Hospital of China Academy of Chinese Medical Sciences, Beijing 100102, 7Department of Acupuncture, Second. Affiliated Hospital of Tianjin University of TCM, Tianjin, 300150, 8Department of Urology, Dongfang Hospital of Beijing. University of Chinese Medicine, Beijing, 100078, China. *For correspondence: ...

  8. Exertional Rhabdomyolysis: What Is It and Why Should We Care?

    Thomas, David Q.; Carlson, Kelli A.; Marzano, Amy; Garrahy, Deborah

    2012-01-01

    Exertional rhabdomyolysis gained increased attention recently when 13 football players from the University of Iowa developed this condition after an especially demanding practice session and were hospitalized. Exertional rhabdomyolysis may lead to severe kidney stress, kidney failure, and even sudden death. Anyone who does physical exercise at a…

  9. 20 CFR 404.1567 - Physical exertion requirements.

    2010-04-01

    ... activities. If someone can do light work, we determine that he or she can also do sedentary work, unless... Physical exertion requirements. To determine the physical exertion requirements of work in the national... making disability determinations under this subpart, we use the following definitions: (a) Sedentary work...

  10. 20 CFR 416.967 - Physical exertion requirements.

    2010-04-01

    ... activities. If someone can do light work, we determine that he or she can also do sedentary work, unless... Physical exertion requirements. To determine the physical exertion requirments of work in the national... making disability determinations under this subpart, we use the following definitions: (a) Sedentary work...

  11. Influence of White-Coat Hypertension on Left Ventricular Deformation 2- and 3-Dimensional Speckle Tracking Study.

    Tadic, Marijana; Cuspidi, Cesare; Ivanovic, Branislava; Ilic, Irena; Celic, Vera; Kocijancic, Vesna

    2016-03-01

    We sought to compare left ventricular deformation in subjects with white-coat hypertension to normotensive and sustained hypertensive patients. This cross-sectional study included 139 untreated subjects who underwent 24-hour ambulatory blood pressure monitoring and completed 2- and 3-dimensional examination. Two-dimensional left ventricular multilayer strain analysis was also performed. White-coat hypertension was diagnosed if clinical blood pressure was elevated and 24-hour blood pressure was normal. Our results showed that left ventricular longitudinal and circumferential strains gradually decreased from normotensive controls across subjects with white-coat hypertension to sustained hypertensive group. Two- and 3-dimensional left ventricular radial strain, as well as 3-dimensional area strain, was not different between groups. Two-dimensional left ventricular longitudinal and circumferential strains of subendocardial and mid-myocardial layers gradually decreased from normotensive control to sustained hypertensive group. Longitudinal and circumferential strains of subepicardial layer did not differ between the observed groups. We concluded that white-coat hypertension significantly affects left ventricular deformation assessed by 2-dimensional traditional strain, multilayer strain, and 3-dimensional strain. © 2016 American Heart Association, Inc.

  12. Quantified Facial Soft-tissue Strain in Animation Measured by Real-time Dynamic 3-Dimensional Imaging

    Vivian M. Hsu, MD

    2014-09-01

    Conclusions: This pilot study illustrates that the face can be objectively and quantitatively evaluated using dynamic major strain analysis. The technology of 3-dimensional optical imaging can be used to advance our understanding of facial soft-tissue dynamics and the effects of animation on facial strain over time.

  13. Characterization of the 3-dimensional microstructure of a graphite negative electrode from a Li-ion battery

    Shearing, P.R.; Howard, L.E.; Jørgensen, Peter Stanley

    2010-01-01

    The 3-dimensional microstructure of a porous electrode from a lithium-ion battery has been characterized for the first time. We use X-ray tomography to reconstruct a 43 × 348 × 478 μm sample volume with voxel dimensions of 480 nm, subsequent division of the reconstructed volumes into sub...

  14. Overview of 3-year experience with large-scale electronic portal imaging device-based 3-dimensional transit dosimetry

    Mijnheer, Ben J.; González, Patrick; Olaciregui-Ruiz, Igor; Rozendaal, Roel A.; van Herk, Marcel; Mans, Anton

    2015-01-01

    To assess the usefulness of electronic portal imaging device (EPID)-based 3-dimensional (3D) transit dosimetry in a radiation therapy department by analyzing a large set of dose verification results. In our institution, routine in vivo dose verification of all treatments is performed by means of 3D

  15. Use of dynamic 3-dimensional transvaginal and transrectal ultrasonography to assess posterior pelvic floor dysfunction related to obstructed defecation.

    Murad-Regadas, Sthela M; Regadas Filho, Francisco Sergio Pinheiro; Regadas, Francisco Sergio Pinheiro; Rodrigues, Lusmar Veras; de J R Pereira, Jacyara; da S Fernandes, Graziela Olivia; Dealcanfreitas, Iris Daiana; Mendonca Filho, Jose Jader

    2014-02-01

    New ultrasound techniques may complement current diagnostic tools, and combined techniques may help to overcome the limitations of individual techniques for the diagnosis of anorectal dysfunction. A high degree of agreement has been demonstrated between echodefecography (dynamic 3-dimensional anorectal ultrasonography) and conventional defecography. Our aim was to evaluate the ability of a combined approach consisting of dynamic 3-dimensional transvaginal and transrectal ultrasonography by using a 3-dimensional biplane endoprobe to assess posterior pelvic floor dysfunctions related to obstructed defecation syndrome in comparison with echodefecography. This was a prospective, observational cohort study conducted at a tertiary-care hospital. Consecutive female patients with symptoms of obstructed defecation were eligible. Each patient underwent assessment of posterior pelvic floor dysfunctions with a combination of dynamic 3-dimensional transvaginal and transrectal ultrasonography by using a biplane transducer and with echodefecography. Kappa (κ) was calculated as an index of agreement between the techniques. Diagnostic accuracy (sensitivity, specificity, and positive and negative predictive values) of the combined technique in detection of posterior dysfunctions was assessed with echodefecography as the standard for comparison. A total of 33 women were evaluated. Substantial agreement was observed regarding normal relaxation and anismus. In detecting the absence or presence of rectocele, the 2 methods agreed in all cases. Near-perfect agreement was found for rectocele grade I, grade II, and grade III. Perfect agreement was found for entero/sigmoidocele, with near-perfect agreement for rectal intussusception. Using echodefecography as the standard for comparison, we found high diagnostic accuracy of transvaginal and transrectal ultrasonography in the detection of posterior dysfunctions. This combined technique should be compared with other dynamic techniques and

  16. Optical Coherence Tomography Angiography for Assessment of the 3-Dimensional Structures of Polypoidal Choroidal Vasculopathy.

    Chi, Yu-Tien; Yang, Chang-Hao; Cheng, Cheng-Kuo

    2017-12-01

    Investigating the quantitative 3-dimensional (3-D) anatomy of polypoidal complex is important for a better understanding of the pathogenesis of polypoidal choroidal vasculopathy (PCV). To quantitatively evaluate the 3-D characteristics of polypoidal structures, branching vascular networks (BVNs), and origin of PCV using optical coherence tomography angiography (OCTA) and multiple image systems. A prospective, observational study was conducted in 47 consecutive Taiwanese patients (47 eyes) from May 21, 2015, to April 30, 2017. All participants were scanned with the Optovue-RTVue-XR-Avanti OCTA system. Patients in whom PCV was identified on OCTA were examined to define characteristics and structures of the original spouting vessels (stalks) from the choroid, polypoidal structures, and BVNs on OCTA. Quantitative analysis of 3-D structures of the polypoidal complex. Among the 47 patients, the mean (SD) patient age was 68.9 (8.0) years, and 28 (59.6%) men were included. Clear images of polypoidal structures could be detected in 17 eyes (36.2%, 22 polypoidal structures), BVNs in 26 eyes (55.3%, 26 tufts of BVNs), and stalks of origin from the choroid in 26 eyes (55.3%, 26 stalks) on the en face plane on OCTA. All polypoidal structures were found at a mean (SD) height of 45.3 (36.1) μm above the retinal pigment epithelium (RPE) reference plane that was preset by the machine, while the BVNs were found at a mean (SD) depth of 28.6 (14.2) μm below the RPE reference plane and the choroidal stalks at 80.4 (24.4) μm below RPE reference plane. The mean (SD) thickness of polypoidal structures was 38.4 (15.5) μm and of BVNs, 60.2 (25.0) μm. The polypoidal structures were all above the Bruch membrane within the dome of the RPE detachment, the choroidal stalks were all in the choroid layer. The BVNs could be either above (up to 18 μm), within, or below (up to 28 μm) the Bruch membrane and were in proximity to the double layers of flattened RPE detachment. These results

  17. SCEC-VDO: A New 3-Dimensional Visualization and Movie Making Software for Earth Science Data

    Milner, K. R.; Sanskriti, F.; Yu, J.; Callaghan, S.; Maechling, P. J.; Jordan, T. H.

    2016-12-01

    Researchers and undergraduate interns at the Southern California Earthquake Center (SCEC) have created a new 3-dimensional (3D) visualization software tool called SCEC Virtual Display of Objects (SCEC-VDO). SCEC-VDO is written in Java and uses the Visualization Toolkit (VTK) backend to render 3D content. SCEC-VDO offers advantages over existing 3D visualization software for viewing georeferenced data beneath the Earth's surface. Many popular visualization packages, such as Google Earth, restrict the user to views of the Earth from above, obstructing views of geological features such as faults and earthquake hypocenters at depth. SCEC-VDO allows the user to view data both above and below the Earth's surface at any angle. It includes tools for viewing global earthquakes from the U.S. Geological Survey, faults from the SCEC Community Fault Model, and results from the latest SCEC models of earthquake hazards in California including UCERF3 and RSQSim. Its object-oriented plugin architecture allows for the easy integration of new regional and global datasets, regardless of the science domain. SCEC-VDO also features rich animation capabilities, allowing users to build a timeline with keyframes of camera position and displayed data. The software is built with the concept of statefulness, allowing for reproducibility and collaboration using an xml file. A prior version of SCEC-VDO, which began development in 2005 under the SCEC Undergraduate Studies in Earthquake Information Technology internship, used the now unsupported Java3D library. Replacing Java3D with the widely supported and actively developed VTK libraries not only ensures that SCEC-VDO can continue to function for years to come, but allows for the export of 3D scenes to web viewers and popular software such as Paraview. SCEC-VDO runs on all recent 64-bit Windows, Mac OS X, and Linux systems with Java 8 or later. More information, including downloads, tutorials, and example movies created fully within SCEC-VDO is

  18. Scaling analyses of the spectral dimension in 3-dimensional causal dynamical triangulations

    Cooperman, Joshua H.

    2018-05-01

    The spectral dimension measures the dimensionality of a space as witnessed by a diffusing random walker. Within the causal dynamical triangulations approach to the quantization of gravity (Ambjørn et al 2000 Phys. Rev. Lett. 85 347, 2001 Nucl. Phys. B 610 347, 1998 Nucl. Phys. B 536 407), the spectral dimension exhibits novel scale-dependent dynamics: reducing towards a value near 2 on sufficiently small scales, matching closely the topological dimension on intermediate scales, and decaying in the presence of positive curvature on sufficiently large scales (Ambjørn et al 2005 Phys. Rev. Lett. 95 171301, Ambjørn et al 2005 Phys. Rev. D 72 064014, Benedetti and Henson 2009 Phys. Rev. D 80 124036, Cooperman 2014 Phys. Rev. D 90 124053, Cooperman et al 2017 Class. Quantum Grav. 34 115008, Coumbe and Jurkiewicz 2015 J. High Energy Phys. JHEP03(2015)151, Kommu 2012 Class. Quantum Grav. 29 105003). I report the first comprehensive scaling analysis of the small-to-intermediate scale spectral dimension for the test case of the causal dynamical triangulations of 3-dimensional Einstein gravity. I find that the spectral dimension scales trivially with the diffusion constant. I find that the spectral dimension is completely finite in the infinite volume limit, and I argue that its maximal value is exactly consistent with the topological dimension of 3 in this limit. I find that the spectral dimension reduces further towards a value near 2 as this case’s bare coupling approaches its phase transition, and I present evidence against the conjecture that the bare coupling simply sets the overall scale of the quantum geometry (Ambjørn et al 2001 Phys. Rev. D 64 044011). On the basis of these findings, I advance a tentative physical explanation for the dynamical reduction of the spectral dimension observed within causal dynamical triangulations: branched polymeric quantum geometry on sufficiently small scales. My analyses should facilitate attempts to employ the spectral

  19. 3-Dimensional numerical simulations of the dynamics of the Venusian mesosphere and thermosphere

    Tingle, S.; Mueller-Wodarg, I. C.

    2009-12-01

    We present the first results from a new 3-dimensional numerical simulation of the steady state dynamics of the Venusian mesosphere and thermosphere (60-300 km). We have adapted the dynamical core of the Titan thermosphere global circulation model (GCM) [1] to a steady state background atmosphere. Our background atmosphere is derived from a hydrostatic combination of the VTS3 [2] and Venus International Reference Atmosphere (VIRA) [3] empirical models, which are otherwise discontinuous at their 100 km interface. We use 4th order polynomials to link the VTS3 and VIRA thermal profiles and employ hydrostatic balance to derive a consistent density profile. We also present comparisons of our background atmosphere to data from the ESA Venus Express Mission. The thermal structure of the Venusian mesosphere is relatively well documented; however, direct measurements of wind speeds are limited. Venus’ slow rotation results in a negligible Coriolis force. This suggests that the zonal circulation should arise from cyclostrophic balance; where the equatorward component of the centrifugal force balances poleward meridional pressure gradients [4]. The sparseness of direct and in-situ measurements has resulted in the application of cyclostrophic balance to measured thermal profiles to derive wind speeds [5] [6] [7] [8]. However, cyclostrophic balance is only strictly valid at mid latitudes (˜ ± 30-75°) and its applicability to the Venusian mesosphere has not been conclusively demonstrated. Our simulations, by solving the full Navier-Stokes momentum equation, will enable us assess the validity of cyclostrophic balance as a description of mesospheric dynamics. This work is part of an ongoing project to develop the first GCM to encompass the atmosphere from the cloud tops into the thermosphere. When complete, this model will enable self-consistent calculations of the dynamics, energy and composition of the atmosphere. It will thus provide a framework to address many of the

  20. Serial Changes in 3-Dimensional Supraspinatus Muscle Volume After Rotator Cuff Repair.

    Chung, Seok Won; Oh, Kyung-Soo; Moon, Sung Gyu; Kim, Na Ra; Lee, Ji Whan; Shim, Eungjune; Park, Sehyung; Kim, Youngjun

    2017-08-01

    There is considerable debate on the recovery of rotator cuff muscle atrophy after rotator cuff repair. To evaluate the serial changes in supraspinatus muscle volume after rotator cuff repair by using semiautomatic segmentation software and to determine the relationship with functional outcomes. Case series; Level of evidence, 4. Seventy-four patients (mean age, 62.8 ± 8.8 years) who underwent arthroscopic rotator cuff repair and obtained 3 consecutive (preoperatively, immediately postoperatively, and later postoperatively [≥1 year postoperatively]) magnetic resonance imaging (MRI) scans having complete Y-views were included. We generated a 3-dimensional (3D) reconstructed model of the supraspinatus muscle by using in-house semiautomatic segmentation software (ITK-SNAP) and calculated both the 2-dimensional (2D) cross-sectional area and 3D volume of the muscle in 3 different views (Y-view, 1 cm medial to the Y-view [Y+1 view], and 2 cm medial to the Y-view [Y+2 view]) at the 3 time points. The area and volume changes at each time point were evaluated according to repair integrity. Later postoperative volumes were compared with immediately postoperative volumes, and their relationship with various clinical factors and the effect of higher volume increases on range of motion, muscle power, and visual analog scale pain and American Shoulder and Elbow Surgeons scores were evaluated. The interrater reliabilities were excellent for all measurements. Areas and volumes increased immediately postoperatively as compared with preoperatively; however, only volumes on the Y+1 view and Y+2 view significantly increased later postoperatively as compared with immediately postoperatively ( P < .05). There were 9 patients with healing failure, and area and volume changes were significantly less later postoperatively compared with immediately postoperatively at all measurement points in these patients ( P < .05). After omitting the patients with healing failure, volume increases

  1. Morphologic evaluation and classification of facial asymmetry using 3-dimensional computed tomography.

    Baek, Chaehwan; Paeng, Jun-Young; Lee, Janice S; Hong, Jongrak

    2012-05-01

    A systematic classification is needed for the diagnosis and surgical treatment of facial asymmetry. The purposes of this study were to analyze the skeletal structures of patients with facial asymmetry and to objectively classify these patients into groups according to these structural characteristics. Patients with facial asymmetry and recent computed tomographic images from 2005 through 2009 were included in this study, which was approved by the institutional review board. Linear measurements, angles, and reference planes on 3-dimensional computed tomograms were obtained, including maxillary (upper midline deviation, maxilla canting, and arch form discrepancy) and mandibular (menton deviation, gonion to midsagittal plane, ramus height, and frontal ramus inclination) measurements. All measurements were analyzed using paired t tests with Bonferroni correction followed by K-means cluster analysis using SPSS 13.0 to determine an objective classification of facial asymmetry in the enrolled patients. Kruskal-Wallis test was performed to verify differences among clustered groups. P < .05 was considered statistically significant. Forty-three patients (18 male, 25 female) were included in the study. They were classified into 4 groups based on cluster analysis. Their mean age was 24.3 ± 4.4 years. Group 1 included subjects (44% of patients) with asymmetry caused by a shift or lateralization of the mandibular body. Group 2 included subjects (39%) with a significant difference between the left and right ramus height with menton deviation to the short side. Group 3 included subjects (12%) with atypical asymmetry, including deviation of the menton to the short side, prominence of the angle/gonion on the larger side, and reverse maxillary canting. Group 4 included subjects (5%) with severe maxillary canting, ramus height differences, and menton deviation to the short side. In this study, patients with asymmetry were classified into 4 statistically distinct groups according to

  2. Characterization of chemical contaminants generated by a desktop fused deposition modeling 3-dimensional Printer.

    Stefaniak, Aleksandr B; LeBouf, Ryan F; Yi, Jinghai; Ham, Jason; Nurkewicz, Timothy; Schwegler-Berry, Diane E; Chen, Bean T; Wells, J Raymond; Duling, Matthew G; Lawrence, Robert B; Martin, Stephen B; Johnson, Alyson R; Virji, M Abbas

    2017-07-01

    Printing devices are known to emit chemicals into the indoor atmosphere. Understanding factors that influence release of chemical contaminants from printers is necessary to develop effective exposure assessment and control strategies. In this study, a desktop fused deposition modeling (FDM) 3-dimensional (3-D) printer using acrylonitrile butadiene styrene (ABS) or polylactic acid (PLA) filaments and two monochrome laser printers were evaluated in a 0.5 m 3 chamber. During printing, chamber air was monitored for vapors using a real-time photoionization detector (results expressed as isobutylene equivalents) to measure total volatile organic compound (TVOC) concentrations, evacuated canisters to identify specific VOCs by off-line gas chromatography-mass spectrometry (GC-MS) analysis, and liquid bubblers to identify carbonyl compounds by GC-MS. Airborne particles were collected on filters for off-line analysis using scanning electron microscopy with an energy dispersive x-ray detector to identify elemental constituents. For 3-D printing, TVOC emission rates were influenced by a printer malfunction, filament type, and to a lesser extent, by filament color; however, rates were not influenced by the number of printer nozzles used or the manufacturer's provided cover. TVOC emission rates were significantly lower for the 3-D printer (49-3552 µg h -1 ) compared to the laser printers (5782-7735 µg h -1 ). A total of 14 VOCs were identified during 3-D printing that were not present during laser printing. 3-D printed objects continued to off-gas styrene, indicating potential for continued exposure after the print job is completed. Carbonyl reaction products were likely formed from emissions of the 3-D printer, including 4-oxopentanal. Ultrafine particles generated by the 3-D printer using ABS and a laser printer contained chromium. Consideration of the factors that influenced the release of chemical contaminants (including known and suspected asthmagens such as styrene and

  3. [Constructing 3-dimensional colorized digital dental model assisted by digital photography].

    Ye, Hong-qiang; Liu, Yu-shu; Liu, Yun-song; Ning, Jing; Zhao, Yi-jiao; Zhou, Yong-sheng

    2016-02-18

    To explore a method of constructing universal 3-dimensional (3D) colorized digital dental model which can be displayed and edited in common 3D software (such as Geomagic series), in order to improve the visual effect of digital dental model in 3D software. The morphological data of teeth and gingivae were obtained by intra-oral scanning system (3Shape TRIOS), constructing 3D digital dental models. The 3D digital dental models were exported as STL files. Meanwhile, referring to the accredited photography guide of American Academy of Cosmetic Dentistry (AACD), five selected digital photographs of patients'teeth and gingivae were taken by digital single lens reflex camera (DSLR) with the same exposure parameters (except occlusal views) to capture the color data. In Geomagic Studio 2013, after STL file of 3D digital dental model being imported, digital photographs were projected on 3D digital dental model with corresponding position and angle. The junctions of different photos were carefully trimmed to get continuous and natural color transitions. Then the 3D colorized digital dental model was constructed, which was exported as OBJ file or WRP file which was a special file for software of Geomagic series. For the purpose of evaluating the visual effect of the 3D colorized digital model, a rating scale on color simulation effect in views of patients'evaluation was used. Sixteen patients were recruited and their scores on colored and non-colored digital dental models were recorded. The data were analyzed using McNemar-Bowker test in SPSS 20. Universal 3D colorized digital dental model with better color simulation was constructed based on intra-oral scanning and digital photography. For clinical application, the 3D colorized digital dental models, combined with 3D face images, were introduced into 3D smile design of aesthetic rehabilitation, which could improve the patients' cognition for the esthetic digital design and virtual prosthetic effect. Universal 3D colorized

  4. Effect of Stereoscopic Anaglyphic 3-Dimensional Video Didactics on Learning Neuroanatomy.

    Goodarzi, Amir; Monti, Sara; Lee, Darrin; Girgis, Fady

    2017-11-01

    The teaching of neuroanatomy in medical education has historically been based on didactic instruction, cadaveric dissections, and intraoperative experience for students. Multiple novel 3-dimensional (3D) modalities have recently emerged. Among these, stereoscopic anaglyphic video is easily accessible and affordable, however, its effects have not yet formally been investigated. This study aimed to investigate if 3D stereoscopic anaglyphic video instruction in neuroanatomy could improve learning for content-naive students, as compared with 2-dimensional (2D) video instruction. A single-site controlled prospective case control study was conducted at the School of Education. Content knowledge was assessed at baseline, followed by the presentation of an instructional neuroanatomy video. Participants viewed the video in either 2D or 3D format and then completed a written test of skull base neuroanatomy. Pretest and post-test performances were analyzed with independent Student's t-tests and analysis of covariance. Our study was completed by 249 subjects. At baseline, the 2D (n = 124, F = 97) and 3D groups (n = 125, F = 96) were similar, although the 3D group was older by 1.7 years (P = 0.0355) and the curricula of participating classes differed (P < 0.0001). Average scores for the 3D group were higher for both pretest (2D, M = 19.9%, standard deviation [SD] = 12.5% vs. 3D, M = 23.9%, SD = 14.9%, P = 0.0234) and post-test performances (2D, M = 68.5%, SD = 18.6% vs. 3D, M = 77.3%, SD = 18.8%, P = 0.003), but the magnitude of improvement across groups did not reach statistical significance (2D, M = 48.7%, SD = 21.3%, vs. 3D, M = 53.5%, SD = 22.7%, P = 0.0855). Incorporation of 3D video instruction into curricula without careful integration is insufficient to promote learning over 2D video. Published by Elsevier Inc.

  5. Measurement of the buccolingual inclination of teeth: manual technique vs 3-dimensional software.

    Nouri, Mahtab; Abdi, Amir Hossein; Farzan, Arash; Mokhtarpour, Faraneh; Baghban, AliReza Akbarzadeh

    2014-10-01

    In this study, we aimed to measure the inclination of teeth on dental casts by a manual technique with the tooth inclination protractor (TIP; MBI, Newport, United Kingdom) and a newly designed 3-dimensional (3D) software program. The correlation of the 2 techniques was evaluated, and the reliability of each technique was assessed separately. This study was conducted on 36 dental casts of normal, well-aligned Class I occlusions; we assessed 432 teeth. All casts had a normal Class I occlusion. After determining the facial axis of the clinical crown and the facial axis points on the dental casts, we measured the inclinations of the incisors and posterior teeth up to the first molars in each dental arch relative to Andrews' occlusal plane and the posterior occlusal plane using the TIP. Moreover, the casts were scanned by a structured-light 3D scanner. The inclination of teeth relative to the occlusal plane was determined using the new software. To assess the reliability, measurements of all teeth from 15 casts were repeated twice by the 2 methods. Intraclass correlation coefficient and Dahlberg's formula were used for calculation of correlation and reliability. Overall, the 2 techniques were not significantly different in the measurements of the inclinations of the teeth in both jaws. The ranges of Dahlberg's formula were 3.1° to 5.8° for the maxilla and 3.3° to 5.9° for the mandible. The overall correlation of the 2 techniques according to the intraclass correlation coefficient was 0.91. For calculation of reliability, the intraclass correlation coefficients for the TIP and the 3D method were 0.73 and 0.82, respectively. The TIP and the 3D software showed a high correlation for measurement of the inclinations of maxillary and mandibular teeth relative to the occlusal plane. Also, the reproducibility of the measurements in each method was high. Copyright © 2014 American Association of Orthodontists. Published by Elsevier Inc. All rights reserved.

  6. Absolute quantification of myocardial blood flow with 13N-ammonia and 3-dimensional PET.

    Schepis, Tiziano; Gaemperli, Oliver; Treyer, Valerie; Valenta, Ines; Burger, Cyrill; Koepfli, Pascal; Namdar, Mehdi; Adachi, Itaru; Alkadhi, Hatem; Kaufmann, Philipp A

    2007-11-01

    The aim of this study was to compare 2-dimensional (2D) and 3-dimensional (3D) dynamic PET for the absolute quantification of myocardial blood flow (MBF) with (13)N-ammonia ((13)N-NH(3)). 2D and 3D MBF measurements were collected from 21 patients undergoing cardiac evaluation at rest (n = 14) and during standard adenosine stress (n = 7). A lutetium yttrium oxyorthosilicate-based PET/CT system with retractable septa, enabling the sequential acquisition of 2D and 3D images within the same patient and study, was used. All 2D studies were performed by injecting 700-900 MBq of (13)N-NH(3). For 14 patients, 3D studies were performed with the same injected (13)N-NH(3) dose as that used in 2D studies. For the remaining 7 patients, 3D images were acquired with a lower dose of (13)N-NH(3), that is, 500 MBq. 2D images reconstructed by use of filtered backprojection (FBP) provided the reference standard for MBF measurements. 3D images were reconstructed by use of Fourier rebinning (FORE) with FBP (FORE-FBP), FORE with ordered-subsets expectation maximization (FORE-OSEM), and a reprojection algorithm (RP). Global MBF measurements derived from 3D PET with FORE-FBP (r = 0.97), FORE-OSEM (r = 0.97), and RP (r = 0.97) were well correlated with those derived from 2D FBP (all Ps measurements between 3D FORE-FBP and 2D FBP and between 3D FORE-OSEM and 2D FBP were 0.01 +/- 0.14 and 0.01 +/- 0.15 mL/min/g, respectively. The mean +/- SD difference in global MBF measurements between 3D RP and 2D FBP was 0.00 +/- 0.16 mL/min/g. The best correlation between 2D PET and 3D PET performed with the lower injected activity was found for the 3D FORE-FBP reconstruction algorithm (r = 0.95, P measurements of MBF with 3D PET and (13)N-NH(3) were in excellent agreement with those obtained with the 2D technique, even when a lower activity was injected.

  7. Exertional headache and coronary ischemia despite normal electrocardiographic stress testing.

    Cutrer, F Michael; Huerter, Karina

    2006-01-01

    Exertional headaches may under certain conditions reflect coronary ischemia. We report the case of a patient seen in a neurology referral practice whose exertional headaches, even in the face of two normal electrocardiographic stress tests and in the absence of underlying chest pain were the sole symptoms of coronary ischemia as detected by Tc-99m Sestamibi testing SPECT stress testing. Stent placement resulted in complete resolution of headaches. Exertional headache in the absence of chest pain may reflect underlying symptomatic coronary artery disease (CAD) even when conventional electrocardiographic stress testing does not indicate ischemia.

  8. 3-Dimensional culture systems for anti-cancer compound profiling and high-throughput screening reveal increases in EGFR inhibitor-mediated cytotoxicity compared to monolayer culture systems.

    Howes, Amy L; Richardson, Robyn D; Finlay, Darren; Vuori, Kristiina

    2014-01-01

    3-dimensional (3D) culture models have the potential to bridge the gap between monolayer cell culture and in vivo studies. To benefit anti-cancer drug discovery from 3D models, new techniques are needed that enable their use in high-throughput (HT) screening amenable formats. We have established miniaturized 3D culture methods robust enough for automated HT screens. We have applied these methods to evaluate the sensitivity of normal and tumorigenic breast epithelial cell lines against a panel of oncology drugs when cultured as monolayers (2D) and spheroids (3D). We have identified two classes of compounds that exhibit preferential cytotoxicity against cancer cells over normal cells when cultured as 3D spheroids: microtubule-targeting agents and epidermal growth factor receptor (EGFR) inhibitors. Further improving upon our 3D model, superior differentiation of EC50 values in the proof-of-concept screens was obtained by co-culturing the breast cancer cells with normal human fibroblasts and endothelial cells. Further, the selective sensitivity of the cancer cells towards chemotherapeutics was observed in 3D co-culture conditions, rather than as 2D co-culture monolayers, highlighting the importance of 3D cultures. Finally, we examined the putative mechanisms that drive the differing potency displayed by EGFR inhibitors. In summary, our studies establish robust 3D culture models of human cells for HT assessment of tumor cell-selective agents. This methodology is anticipated to provide a useful tool for the study of biological differences within 2D and 3D culture conditions in HT format, and an important platform for novel anti-cancer drug discovery.

  9. Sex Differences in Patients With CAM Deformities With Femoroacetabular Impingement: 3-Dimensional Computed Tomographic Quantification.

    Yanke, Adam B; Khair, M Michael; Stanley, Robert; Walton, David; Lee, Simon; Bush-Joseph, Charles A; Espinoza Orías, Alejandro; Espinosa Orias, Alejandro A; Inoue, Nozomu; Nho, Shane J

    2015-12-01

    To determine if significant differences exist between male and female CAM deformities using quantitative 3-dimensional (3D) volume and location analysis. Retrospective analysis of preoperative computed tomographic (CT) scans for 138 femurs (69 from male patients and 69 from female patients) diagnosed with impingement from November 2009 to November 2011 was completed. Those patients who presented with hip complaints and had a history, physical examination (limited range of motion, positive impingement signs), plain radiographs (anteroposterior pelvis, 90° Dunn view, false profile view), and magnetic resonance images consistent with femoroacetabular impingement (FAI) and in whom a minimum of 6 months of conservative therapy (oral anti-inflammatory agents, physical therapy, and activity modification) had failed were indicated for arthroscopic surgery and had a preoperative CT scan. Scans were segmented, converted to point cloud data, and analyzed with a custom-written computer program. Analysis included mean CAM height and volume, head radius, and femoral version. Differences were analyzed using an unpaired t test with significance set at P position ± the 2:51 o'clock position to the 3:28 o'clock position ± the 1:59 o'clock position, with an average span from the 3:06 o'clock position ± the 1:29 o'clock position (male patients, the 11:23 o'clock position ± the 0:46 o'clock position to the 3:05 o'clock position ± the 1:20 o'clock position; female patients, the 11:33 o'clock position ± the 0:37 o'clock position to the 2:27 o'clock position ± the 0:45 o'clock position). There were no differences in the posterior (P = .60) or anterior (P = .14) extent of CAM deformities. However, the span on the clock face of the CAM deformities varied when comparing men with women (male patients, the 3:43 o'clock position ± the 1:29 o'clock position; female patients, the 2:54 o'clock position ± the 1:09 o'clock position; P = .02). Our data show that female CAM deformities

  10. Exertional rhabdomyolysis: physiological response or manifestation of an underlying myopathy?

    Scalco, R.S.; Snoeck, M.; Quinlivan, R.; Treves, S.; Laforet, P.; Jungbluth, H.; Voermans, N.C.

    2016-01-01

    Exertional rhabdomyolysis is characterised by muscle breakdown associated with strenuous exercise or normal exercise under extreme circumstances. Key features are severe muscle pain and sudden transient elevation of serum creatine kinase (CK) levels with or without associated myoglobinuria. Mild

  11. Editorial Commentary: Single-Image Slice Magnetic Resonance Imaging Assessments Do Not Predict 3-Dimensional Muscle Volume.

    Brand, Jefferson C

    2016-01-01

    No single-image magnetic resonance imaging (MRI) assessment-Goutallier classification, Fuchs classification, or cross-sectional area-is predictive of whole-muscle volume or fatty atrophy of the supraspinatus or infraspinatus. Rather, 3-dimensional MRI measurement of whole-muscle volume and fat-free muscle volume is required and is associated with shoulder strength, which is clinically relevant. Three-dimensional MRI may represent a new gold standard for assessment of the rotator cuff musculature using imaging and may help to predict the feasibility of repair of a rotator cuff tear as well as the postoperative outcome. Unfortunately, 3-dimensional MRI assessment of muscle volume is labor intensive and is not widely available for clinical use. Copyright © 2016 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

  12. 3-dimensional earthquake response analysis of embedded reactor building using hybrid model of boundary elements and finite elements

    Muto, K.; Motosaka, M.; Kamata, M.; Masuda, K.; Urao, K.; Mameda, T.

    1985-01-01

    In order to investigate the 3-dimensional earthquake response characteristics of an embedded structure with consideration for soil-structure interaction, the authors have developed an analytical method using 3-dimensional hybrid model of boundary elements (BEM) and finite elements (FEM) and have conducted a dynamic analysis of an actual nuclear reactor building. This paper describes a comparative study between two different embedment depths in soil as elastic half-space. As the results, it was found that the earthquake response intensity decreases with the increase of the embedment depth and that this method was confirmed to be effective for investigating the 3-D response characteristics of embedded structures such as deflection pattern of each floor level, floor response spectra in high frequency range. (orig.)

  13. Use of 3-dimensional computed tomography to detect a barium-masked fish bone causing esophageal perforation.

    Tsukiyama, Atsushi; Tagami, Takashi; Kim, Shiei; Yokota, Hiroyuki

    2014-01-01

    Computed tomography (CT) is useful for evaluating esophageal foreign bodies and detecting perforation. However, when evaluation is difficult owing to the previous use of barium as a contrast medium, 3-dimensional CT may facilitate accurate diagnosis. A 49-year-old man was transferred to our hospital with the diagnosis of esophageal perforation. Because barium had been used as a contrast medium for an esophagram performed at a previous hospital, horizontal CT and esophageal endoscopy could not be able to identify the foreign body or characterize the lesion. However, 3-dimensional CT clearly revealed an L-shaped foreign body and its anatomical relationships in the mediastinum. Accordingly, we removed the foreign body using an upper gastrointestinal endoscope. The foreign body was the premaxillary bone of a sea bream. The patient was discharged without complications.

  14. The application of 3-dimensional printing for preoperative planning in oral and maxillofacial surgery in dogs and cats

    Winer, JN; Verstraete, FJM; Cissell, DD; Lucero, S; Athanasiou, KA; Arzi, B

    2017-01-01

    © 2017 The American College of Veterinary Surgeons Objective: To describe the application of 3-dimensional (3D) printing in advanced oral and maxillofacial surgery (OMFS) and to discuss the benefits of this modality in surgical planning, student and resident training, and client education. Study design: Retrospective case series. Animals: Client-owned dogs (n = 28) and cats (n = 4) with 3D printing models of the skulls. Methods: The medical records of 32 cases with 3D printing prior to major ...

  15. The feasibility study on 3-dimensional fluorescent x-ray computed tomography using the pinhole effect for biomedical applications.

    Sunaguchi, Naoki; Yuasa, Tetsuya; Hyodo, Kazuyuki; Zeniya, Tsutomu

    2013-01-01

    We propose a 3-dimensional fluorescent x-ray computed tomography (CT) pinhole collimator, aimed at providing molecular imaging with quantifiable measures and sub-millimeter spatial resolution. In this study, we demonstrate the feasibility of this concept and investigate imaging properties such as spatial resolution, contrast resolution and quantifiable measures, by imaging physical phantoms using a preliminary imaging system developed with monochromatic synchrotron x rays constructed at the BLNE-7A experimental line at KEK, Japan.

  16. Do placebo expectations influence perceived exertion during physical exercise?

    Hendrik Mothes

    Full Text Available This study investigates the role of placebo expectations in individuals' perception of exertion during acute physical exercise. Building upon findings from placebo and marketing research, we examined how perceived exertion is affected by expectations regarding a the effects of exercise and b the effects of the exercise product worn during the exercise. We also investigated whether these effects are moderated by physical self-concept. Seventy-eight participants conducted a moderate 30 min cycling exercise on an ergometer, with perceived exertion (RPE measured every 5 minutes. Beforehand, each participant was randomly assigned to 1 of 4 conditions and watched a corresponding film clip presenting "scientific evidence" that the exercise would or would not result in health benefits and that the exercise product they were wearing (compression garment would additionally enhance exercise benefits or would only be worn for control purposes. Participants' physical self-concept was assessed via questionnaire. Results partially demonstrated that participants with more positive expectations experienced reduced perceived exertion during the exercise. Furthermore, our results indicate a moderator effect of physical self-concept: Individuals with a high physical self-concept benefited (in terms of reduced perceived exertion levels in particular from an induction of generally positive expectations. In contrast, individuals with a low physical self-concept benefited when positive expectations were related to the exercise product they were wearing. In sum, these results suggest that placebo expectations may be a further, previously neglected class of psychological factors that influence the perception of exertion.

  17. Musical agency reduces perceived exertion during strenuous physical performance.

    Fritz, Thomas Hans; Hardikar, Samyogita; Demoucron, Matthias; Niessen, Margot; Demey, Michiel; Giot, Olivier; Li, Yongming; Haynes, John-Dylan; Villringer, Arno; Leman, Marc

    2013-10-29

    Music is known to be capable of reducing perceived exertion during strenuous physical activity. The current interpretation of this modulating effect of music is that music may be perceived as a diversion from unpleasant proprioceptive sensations that go along with exhaustion. Here we investigated the effects of music on perceived exertion during a physically strenuous task, varying musical agency, a task that relies on the experience of body proprioception, rather than simply diverting from it. For this we measured psychologically indicated exertion during physical workout with and without musical agency while simultaneously acquiring metabolic values with spirometry. Results showed that musical agency significantly decreased perceived exertion during workout, indicating that musical agency may actually facilitate physically strenuous activities. This indicates that the positive effect of music on perceived exertion cannot always be explained by an effect of diversion from proprioceptive feedback. Furthermore, this finding suggests that the down-modulating effect of musical agency on perceived exertion may be a previously unacknowledged driving force for the development of music in humans: making music makes strenuous physical activities less exhausting.

  18. Intracellular trafficking of superparamagnetic iron oxide nanoparticles conjugated with TAT peptide: 3-dimensional electron tomography analysis

    Nair, Baiju G.; Fukuda, Takahiro; Mizuki, Toru; Hanajiri, Tatsuro [Bio-Nano Electronics Research Centre, Toyo University, Saitama 350-8585 (Japan); Maekawa, Toru, E-mail: maekawa@toyo.jp [Bio-Nano Electronics Research Centre, Toyo University, Saitama 350-8585 (Japan)

    2012-05-18

    Highlights: Black-Right-Pointing-Pointer We study the intracellular localisation of TAT-SPIONs using 3-D electron tomography. Black-Right-Pointing-Pointer 3-D images of TAT-SPIONs in a cell are clearly shown. Black-Right-Pointing-Pointer Release of TAT-SPIONs from endocytic vesicles into the cytoplasm is clearly shown. -- Abstract: Internalisation of nanoparticles conjugated with cell penetrating peptides is a promising approach to various drug delivery applications. Cell penetrating peptides such as transactivating transcriptional activator (TAT) peptides derived from HIV-1 proteins are effective intracellular delivery vectors for a wide range of nanoparticles and pharmaceutical agents thanks to their amicable ability to enter cells and minimum cytotoxicity. Although different mechanisms of intracellular uptake and localisation have been proposed for TAT conjugated nanoparticles, it is necessary to visualise the particles on a 3-D plane in order to investigate the actual intracellular uptake and localisation. Here, we study the intracellular localisation and trafficking of TAT peptide conjugated superparamagnetic ion oxide nanoparticles (TAT-SPIONs) using 3-D electron tomography. 3-D tomograms clearly show the location of TAT-SPIONs in a cell and their slow release from the endocytic vesicles into the cytoplasm. The present methodology may well be utilised for further investigations of the behaviours of nanoparticles in cells and eventually for the development of nano drug delivery systems.

  19. Intracellular trafficking of superparamagnetic iron oxide nanoparticles conjugated with TAT peptide: 3-dimensional electron tomography analysis

    Nair, Baiju G.; Fukuda, Takahiro; Mizuki, Toru; Hanajiri, Tatsuro; Maekawa, Toru

    2012-01-01

    Highlights: ► We study the intracellular localisation of TAT-SPIONs using 3-D electron tomography. ► 3-D images of TAT-SPIONs in a cell are clearly shown. ► Release of TAT-SPIONs from endocytic vesicles into the cytoplasm is clearly shown. -- Abstract: Internalisation of nanoparticles conjugated with cell penetrating peptides is a promising approach to various drug delivery applications. Cell penetrating peptides such as transactivating transcriptional activator (TAT) peptides derived from HIV-1 proteins are effective intracellular delivery vectors for a wide range of nanoparticles and pharmaceutical agents thanks to their amicable ability to enter cells and minimum cytotoxicity. Although different mechanisms of intracellular uptake and localisation have been proposed for TAT conjugated nanoparticles, it is necessary to visualise the particles on a 3-D plane in order to investigate the actual intracellular uptake and localisation. Here, we study the intracellular localisation and trafficking of TAT peptide conjugated superparamagnetic ion oxide nanoparticles (TAT-SPIONs) using 3-D electron tomography. 3-D tomograms clearly show the location of TAT-SPIONs in a cell and their slow release from the endocytic vesicles into the cytoplasm. The present methodology may well be utilised for further investigations of the behaviours of nanoparticles in cells and eventually for the development of nano drug delivery systems.

  20. Designing 3-Dimensional In Vitro Oviduct Culture Systems to Study Mammalian Fertilization and Embryo Production.

    Ferraz, Marcia A M M; Henning, Heiko H W; Stout, Tom A E; Vos, Peter L A M; Gadella, Bart M

    2017-07-01

    The oviduct was long considered a largely passive conduit for gametes and embryos. However, an increasing number of studies into oviduct physiology have demonstrated that it specifically and significantly influences gamete interaction, fertilization and early embryo development. While oviduct epithelial cell (OEC) function has been examined during maintenance in conventional tissue culture dishes, cells seeded into these two-dimensional (2-D) conditions suffer a rapid loss of differentiated OEC characteristics, such as ciliation and secretory activity. Recently, three-dimensional (3-D) cell culture systems have been developed that make use of cell inserts to create basolateral and apical medium compartments with a confluent epithelial cell layer at the interface. Using such 3-D culture systems, OECs can be triggered to redevelop typical differentiated cell properties and levels of tissue organization can be developed that are not possible in a 2-D culture. 3-D culture systems can be further refined using new micro-engineering techniques (including microfluidics and 3-D printing) which can be used to produce 'organs-on-chips', i.e. live 3-D cultures that bio-mimic the oviduct. In this review, concepts for designing bio-mimic 3-D oviduct cultures are presented. The increased possibilities and concomitant challenges when trying to more closely investigate oviduct physiology, gamete activation, fertilization and embryo production are discussed.

  1. Exertional rhabdomyolysis: physiological response or manifestation of an underlying myopathy?

    Scalco, Renata S; Snoeck, Marc; Quinlivan, Ros; Treves, Susan; Laforét, Pascal; Jungbluth, Heinz; Voermans, Nicol C

    2016-01-01

    Exertional rhabdomyolysis is characterised by muscle breakdown associated with strenuous exercise or normal exercise under extreme circumstances. Key features are severe muscle pain and sudden transient elevation of serum creatine kinase (CK) levels with or without associated myoglobinuria. Mild cases may remain unnoticed or undiagnosed. Exertional rhabdomyolysis is well described among athletes and military personnel, but may occur in anybody exposed to unaccustomed exercise. In contrast, exertional rhabdomyolysis may be the first manifestation of a genetic muscle disease that lowers the exercise threshold for developing muscle breakdown. Repeated episodes of exertional rhabdomyolysis should raise the suspicion of such an underlying disorder, in particular in individuals in whom the severity of the rhabdomyolysis episodes exceeds the expected response to the exercise performed. The present review aims to provide a practical guideline for the acute management and postepisode counselling of patients with exertional rhabdomyolysis, with a particular emphasis on when to suspect an underlying genetic disorder. The pathophysiology and its clinical features are reviewed, emphasising four main stepwise approaches: (1) the clinical significance of an acute episode, (2) risks of renal impairment, (3) clinical indicators of an underlying genetic disorders and (4) when and how to recommence sport activity following an acute episode of rhabdomyolysis. Genetic backgrounds that appear to be associated with both enhanced athletic performance and increased rhabdomyolysis risk are briefly reviewed. PMID:27900193

  2. Exertional rhabdomyolysis: physiological response or manifestation of an underlying myopathy?

    Scalco, Renata S; Snoeck, Marc; Quinlivan, Ros; Treves, Susan; Laforét, Pascal; Jungbluth, Heinz; Voermans, Nicol C

    2016-01-01

    Exertional rhabdomyolysis is characterised by muscle breakdown associated with strenuous exercise or normal exercise under extreme circumstances. Key features are severe muscle pain and sudden transient elevation of serum creatine kinase (CK) levels with or without associated myoglobinuria. Mild cases may remain unnoticed or undiagnosed. Exertional rhabdomyolysis is well described among athletes and military personnel, but may occur in anybody exposed to unaccustomed exercise. In contrast, exertional rhabdomyolysis may be the first manifestation of a genetic muscle disease that lowers the exercise threshold for developing muscle breakdown. Repeated episodes of exertional rhabdomyolysis should raise the suspicion of such an underlying disorder, in particular in individuals in whom the severity of the rhabdomyolysis episodes exceeds the expected response to the exercise performed. The present review aims to provide a practical guideline for the acute management and postepisode counselling of patients with exertional rhabdomyolysis, with a particular emphasis on when to suspect an underlying genetic disorder. The pathophysiology and its clinical features are reviewed, emphasising four main stepwise approaches: (1) the clinical significance of an acute episode, (2) risks of renal impairment, (3) clinical indicators of an underlying genetic disorders and (4) when and how to recommence sport activity following an acute episode of rhabdomyolysis. Genetic backgrounds that appear to be associated with both enhanced athletic performance and increased rhabdomyolysis risk are briefly reviewed.

  3. Factors associated with high physical exertion during manual lifting

    Andersen, Lars L.; Sundstrup, Emil; Brandt, Mikkel

    2018-01-01

    BACKGROUND: High physical exertion during work is a risk factor for back pain and long-term sickness absence. OBJECTIVE: To investigate which factors are associated with physical exertion during manual lifting. METHODS: From 14 workplaces across Denmark, 200 blue-collar workers reported perceived...... physical exertion (Borg-CR10) during manual lifting from floor to table height of 5, 10, 20 and 30 kg at the beginning and end of the working day. The workers also responded to a questionnaire and went through testing of isometric back muscle strength. Associations were modelled using logistic regression...... during manual lifting in blue-collar workers. These factors should be considered when planning work with manual lifting for individual workers....

  4. Influence of permittivity on gradient force exerted on Mie spheres.

    Chen, Jun; Li, Kaikai; Li, Xiao

    2018-04-01

    In optical trapping, whether a particle could be stably trapped into the focus region greatly depends on the strength of the gradient force. Individual theoretical study on gradient force exerted on a Mie particle is rare because the mathematical separation of the gradient force and the scattering force in the Mie regime is difficult. Based on the recent forces separation work by Du et al. [Sci. Rep.7, 18042 (2017)SRCEC32045-232210.1038/s41598-017-17874-1], we investigate the influence of permittivity (an important macroscopic physical quantity) on the gradient force exerted on a Mie particle by cooperating numerical calculation using fast Fourier transform and analytical analysis using multipole expansion. It is revealed that gradient forces exerted on small spheres are mainly determined by the electric dipole moment except for certain permittivity with which the real part of polarizability of the electric dipole approaches zero, and gradient forces exerted on larger spheres are complex because of the superposition of the multipole moments. The classification of permittivity corresponding to different varying tendencies of gradient forces exerted on small spheres or larger Mie particles are illustrated. Absorption of particles favors the trapping of small spheres by gradient force, while it is bad for the trapping of larger particles. Moreover, the absolute values of the maximal gradient forces exerted on larger Mie particles decline greatly versus the varied imaginary part of permittivity. This work provides elaborate investigation on the different varying tendencies of gradient forces versus permittivity, which favors more accurate and free optical trapping.

  5. Quantified Facial Soft-tissue Strain in Animation Measured by Real-time Dynamic 3-Dimensional Imaging.

    Hsu, Vivian M; Wes, Ari M; Tahiri, Youssef; Cornman-Homonoff, Joshua; Percec, Ivona

    2014-09-01

    The aim of this study is to evaluate and quantify dynamic soft-tissue strain in the human face using real-time 3-dimensional imaging technology. Thirteen subjects (8 women, 5 men) between the ages of 18 and 70 were imaged using a dual-camera system and 3-dimensional optical analysis (ARAMIS, Trilion Quality Systems, Pa.). Each subject was imaged at rest and with the following facial expressions: (1) smile, (2) laughter, (3) surprise, (4) anger, (5) grimace, and (6) pursed lips. The facial strains defining stretch and compression were computed for each subject and compared. The areas of greatest strain were localized to the midface and lower face for all expressions. Subjects over the age of 40 had a statistically significant increase in stretch in the perioral region while lip pursing compared with subjects under the age of 40 (58.4% vs 33.8%, P = 0.015). When specific components of lip pursing were analyzed, there was a significantly greater degree of stretch in the nasolabial fold region in subjects over 40 compared with those under 40 (61.6% vs 32.9%, P = 0.007). Furthermore, we observed a greater degree of asymmetry of strain in the nasolabial fold region in the older age group (18.4% vs 5.4%, P = 0.03). This pilot study illustrates that the face can be objectively and quantitatively evaluated using dynamic major strain analysis. The technology of 3-dimensional optical imaging can be used to advance our understanding of facial soft-tissue dynamics and the effects of animation on facial strain over time.

  6. Comparison between Radiographic (2-dimensional and 3-dimensional) and Histologic Findings of Periapical Lesions Treated with Apical Surgery.

    Bornstein, Michael M; Bingisser, Andreas C; Reichart, Peter A; Sendi, Pedram; Bosshardt, Dieter D; von Arx, Thomas

    2015-06-01

    The aim of this study was to evaluate the concordance of 2- and 3-dimensional radiography and histopathology in the diagnosis of periapical lesions. Patients were consecutively enrolled in this study provided that preoperative periapical radiography (PR) and cone-beam computed tomographic imaging of the tooth to be treated with apical surgery were performed. The periapical lesional tissue was histologically analyzed by 2 blinded examiners. The final histologic diagnosis was compared with the radiographic assessments of 4 blinded observers. The initial study material included 62 teeth in the same number of patients. Four lesions had to be excluded during processing, resulting in a final number of 58 evaluated cases (31 women and 27 men, mean age = 55 years). The final histologic diagnosis of the periapical lesions included 55 granulomas (94.8%) and 3 cysts (5.2%). Histologic analysis of the tissue samples from the apical lesions exhibited an almost perfect agreement between the 2 experienced investigators with an overall agreement of 94.83% (kappa = 0.8011). Radiographic assessment overestimated cysts by 28.4% (cone-beam computed tomographic imaging) and 20.7% (periapical radiography), respectively. Comparing the correlation of the radiographic diagnosis of 4 observers with the final histologic diagnosis, 2-dimensional (kappa = 0.104) and 3-dimensional imaging (kappa = 0.111) provided only minimum agreement. To establish a final diagnosis of an apical radiolucency, the tissue specimen should be evaluated histologically and specified as a granuloma (with/without epithelium) or a cyst. Analysis of 2-dimensional and 3-dimensional radiographic images alike results only in a tentative diagnosis that should be confirmed with biopsy. Copyright © 2015 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

  7. Designing and manufacturing an auricular prosthesis using computed tomography, 3-dimensional photographic imaging, and additive manufacturing: a clinical report.

    Liacouras, Peter; Garnes, Jonathan; Roman, Norberto; Petrich, Anton; Grant, Gerald T

    2011-02-01

    The method of fabricating an auricular prosthesis by digitally positioning a mirror image of the soft tissue, then designing and using rapid prototyping to produce the mold, can reduce the steps and time needed to create a prosthesis by the traditional approach of sculpting either wax or clay. The purpose of this clinical report is to illustrate how the use of 3-dimensional (3-D) photography, computer technology, and additive manufacturing can extensively reduce many of the preliminary procedures currently used to create an auricular prosthesis. Copyright © 2011 The Editorial Council of the Journal of Prosthetic Dentistry. Published by Mosby, Inc. All rights reserved.

  8. Comparison of personal computer with CT workstation in the evaluation of 3-dimensional CT image of the skull

    Kang, Bok Hee; Kim, Kee Deog; Park, Chang Seo

    2001-01-01

    To evaluate the usefulness of the reconstructed 3-dimensional image on the personal computer in comparison with that of the CT workstation by quantitative comparison and analysis. The spiral CT data obtained from 27 persons were transferred from the CT workstation to a personal computer, and they were reconstructed as 3-dimensional image on the personal computer using V-works 2.0 TM . One observer obtained the 14 measurements on the reconstructed 3-dimensional image on both the CT workstation and the personal computer. Paired test was used to evaluate the intraobserver difference and the mean value of the each measurement on the CT workstation and the personal computer. Pearson correlation analysis and % imcongruence were also performed. I-Gn, N-Gn, N-A, N-Ns, B-A and G-Op did not show any statistically significant difference (p>0.05), B-O, B-N, Eu-Eu, Zy-Zy, Biw, D-D, Orbrd R, and L had statistically significant difference (p<0.05), but the mean values of the differences of all measurements were below 2 mm, except for D-D. The value of correlation coefficient γ was greater than 0.95 at I-Gn, N-Gn, N-A, N-Ns, B-A, B-N, G-Op, Eu-Eu, Zy-Zy, and Biw, and it was 0.75 at B-O, 0.78 at D-D, and 0.82 at both Orbrb R and L. The % incongruence was below 4% at I-Gn, N-Gn, N-A, N-Ns, B-A, B-N, G-Op, Eu-Eu, Zy-Zy, and Biw, and 7.18%, 10.78%, 4.97%, 5.89% at B-O, D-D, Orbrb R and L respectively. It can be considered that the utilization of the personal computer has great usefulness in reconstruction of the 3-dimensional image when it comes to the economics, accessibility and convenience, except for thin bones and the landmarks which and difficult to be located

  9. Stereotactic Ablative Body Radiation Therapy for Primary Kidney Cancer: A 3-Dimensional Conformal Technique Associated With Low Rates of Early Toxicity

    Pham, Daniel, E-mail: daniel.pham@petermac.org [Department of Radiotherapy Services, Peter MacCallum Cancer Centre, Melbourne, Victoria (Australia); Department of Medical Imaging and Radiation Sciences, Monash University, Melbourne, Victoria (Australia); Thompson, Ann [Department of Radiotherapy Services, Peter MacCallum Cancer Centre, Melbourne, Victoria (Australia); Kron, Tomas [Department of Physical Sciences, Peter MacCallum Cancer Centre, Melbourne, Victoria (Australia); Sir Peter MacCallum Department of Oncology, Melbourne University, Melbourne, Victoria (Australia); Foroudi, Farshad [Sir Peter MacCallum Department of Oncology, Melbourne University, Melbourne, Victoria (Australia); Department of Radiation Oncology and Cancer Imaging, Peter MacCallum Cancer Centre, Melbourne, Victoria (Australia); Kolsky, Michal Schneider [Department of Medical Imaging and Radiation Sciences, Monash University, Melbourne, Victoria (Australia); Devereux, Thomas; Lim, Andrew [Department of Radiotherapy Services, Peter MacCallum Cancer Centre, Melbourne, Victoria (Australia); Siva, Shankar [Sir Peter MacCallum Department of Oncology, Melbourne University, Melbourne, Victoria (Australia); Department of Radiation Oncology and Cancer Imaging, Peter MacCallum Cancer Centre, Melbourne, Victoria (Australia)

    2014-12-01

    Purpose: To describe our 3-dimensional conformal planning approaches and report early toxicities with stereotactic body radiation therapy for the management of primary renal cell carcinoma. Methods and Materials: This is an analysis of a phase 1 trial of stereotactic body radiation therapy for primary inoperable renal cell carcinoma. A dose of 42 Gy/3 fractions was prescribed to targets ≥5 cm, whereas for <5 cm 26 Gy/1 fraction was used. All patients underwent a planning 4-dimensional CT to generate a planning target volume (PTV) from a 5-mm isotropic expansion of the internal target volume. Planning required a minimum of 8 fields prescribing to the minimum isodose surrounding the PTV. Intermediate dose spillage at 50% of the prescription dose (R50%) was measured to describe the dose gradient. Early toxicity (<6 months) was scored using the Common Terminology Criteria for Adverse Events (v4.0). Results: From July 2012 to August 2013 a total of 20 patients (median age, 77 years) were recruited into a prospective clinical trial. Eleven patients underwent fractionated treatment and 9 patients a single fraction. For PTV targets <100 cm{sup 3} the median number of beams used was 8 (2 noncoplanar) to achieve an average R50% of 3.7. For PTV targets >100 cm{sup 3} the median beam number used was 10 (4 noncoplanar) for an average R50% value of 4.3. The R50% was inversely proportional to decreasing PTV volume (r=−0.62, P=.003) and increasing total beams used (r=−0.51, P=.022). Twelve of 20 patients (60%) suffered grade ≤2 early toxicity, whereas 8 of 20 patients (40%) were asymptomatic. Nausea, chest wall pain, and fatigue were the most common toxicities reported. Conclusion: A 3-dimensional conformal planning technique of 8-10 beams can be used to deliver highly tolerable stereotactic ablation to primary kidney targets with minimal early toxicities. Ongoing follow-up is currently in place to assess long-term toxicities and cancer control.

  10. 2 and 3 dimensional systems studied using x-ray crystallographic techniques

    Schultz, T. M.

    1998-01-01

    Dodecanethiol is known to self assemble on pure Au(111) surfaces. Grazing incidence X-ray diffraction (GIXD) experiments have been performed on this surface under true equilibrium conditions, using an in-situ cell. In addition an extended ex-situ data set of dodecanethiol on gold has been collected. Finally the structure of the cleaved (OOι) surface of benzamide is presented, based on GIXD measurements. Structural models for tetramethylammonium tetrafluoroborate based on rigid body TLX refinements are presented. A comparison between three different data collection methods is carried out and the appearance of a twinned structure at the 158 K phase transition is discussed. The critical temperature of the phase transition is determined. (au)

  11. A 3-dimensional in vitro model of epithelioid granulomas induced by high aspect ratio nanomaterials

    Hurt Robert H

    2011-05-01

    Full Text Available Abstract Background The most common causes of granulomatous inflammation are persistent pathogens and poorly-degradable irritating materials. A characteristic pathological reaction to intratracheal instillation, pharyngeal aspiration, or inhalation of carbon nanotubes is formation of epithelioid granulomas accompanied by interstitial fibrosis in the lungs. In the mesothelium, a similar response is induced by high aspect ratio nanomaterials, including asbestos fibers, following intraperitoneal injection. This asbestos-like behaviour of some engineered nanomaterials is a concern for their potential adverse health effects in the lungs and mesothelium. We hypothesize that high aspect ratio nanomaterials will induce epithelioid granulomas in nonadherent macrophages in 3D cultures. Results Carbon black particles (Printex 90 and crocidolite asbestos fibers were used as well-characterized reference materials and compared with three commercial samples of multiwalled carbon nanotubes (MWCNTs. Doses were identified in 2D and 3D cultures in order to minimize acute toxicity and to reflect realistic occupational exposures in humans and in previous inhalation studies in rodents. Under serum-free conditions, exposure of nonadherent primary murine bone marrow-derived macrophages to 0.5 μg/ml (0.38 μg/cm2 of crocidolite asbestos fibers or MWCNTs, but not carbon black, induced macrophage differentiation into epithelioid cells and formation of stable aggregates with the characteristic morphology of granulomas. Formation of multinucleated giant cells was also induced by asbestos fibers or MWCNTs in this 3D in vitro model. After 7-14 days, macrophages exposed to high aspect ratio nanomaterials co-expressed proinflammatory (M1 as well as profibrotic (M2 phenotypic markers. Conclusions Induction of epithelioid granulomas appears to correlate with high aspect ratio and complex 3D structure of carbon nanotubes, not with their iron content or surface area. This model

  12. Exertional Heat Illness among Secondary School Athletes: Statewide Policy Implications

    Rodgers, Jill; Slota, Peggy; Zamboni, Beth

    2018-01-01

    Exertional heat illness (EHI) is a leading cause of preventable death among student athletes. While causes and preventative measures for EHI are known, school districts may not be implementing evidence-based practices. This descriptive, exploratory study explored school policies, resources, and practices of coaches in a mid-Atlantic state in the…

  13. Mechanochemistry Induced Using Force Exerted by a Functionalized Microscope Tip

    Zhang, Yajie; Wang, Yongfeng; Lü, Jing-Tao

    2017-01-01

    Atomic-scale mechanochemistry is realized from force exerted by a C60 -functionalized scanning tunneling microscope tip. Two conformers of tin phthalocyanine can be prepared on coinage-metal surfaces. A transition between these conformers is induced on Cu(111) and Ag(100). Density...

  14. Exertional heat illness: emerging concepts and advances in prehospital care.

    Pryor, Riana R; Roth, Ronald N; Suyama, Joe; Hostler, David

    2015-06-01

    Exertional heat illness is a classification of disease with clinical presentations that are not always diagnosed easily. Exertional heat stroke is a significant cause of death in competitive sports, and the increasing popularity of marathons races and ultra-endurance competitions will make treating many heat illnesses more common for Emergency Medical Services (EMS) providers. Although evidence is available primarily from case series and healthy volunteer studies, the consensus for treating exertional heat illness, coupled with altered mental status, is whole body rapid cooling. Cold or ice water immersion remains the most effective treatment to achieve this goal. External thermometry is unreliable in the context of heat stress and direct internal temperature measurement by rectal or esophageal probes must be used when diagnosing heat illness and during cooling. With rapid recognition and implementation of effective cooling, most patients suffering from exertional heat stroke will recover quickly and can be discharged home with instructions to rest and to avoid heat stress and exercise for a minimum of 48 hours; although, further research pertaining to return to activity is warranted.

  15. Forces exerted by jumping children: A pilot study

    Moes, C.C.M.; Bakker, H.E.

    1998-01-01

    This article reports on a pilot study of the loads exerted vertically by children when jumping. The subjects of the study were 17 children, aged from two to twelve years. Measurements were made using video recordings and a force-plate. The influence of the stiffness of the base and of jumping with

  16. Mind the gap : probing exertion experience with experiential design landscapes

    Ren, X.; Lu, Y.; Brombacher, A.C.; Bogers, S.J.A.

    2016-01-01

    In this paper, we report our study on applying Experiential Design Landscapes as the basis of design process to support the design of exertion games. We approach this question by setting up an 8-day interaction design module with 7 groups of students. The methods of our module were developed based

  17. 20 CFR 220.132 - Physical exertion requirements.

    2010-04-01

    ... 20 Employees' Benefits 1 2010-04-01 2010-04-01 false Physical exertion requirements. 220.132 Section 220.132 Employees' Benefits RAILROAD RETIREMENT BOARD REGULATIONS UNDER THE RAILROAD RETIREMENT... of walking and standing is often necessary in carrying out job duties. Jobs are sedentary if walking...

  18. The design of two color interferometer system for the 3-dimensional analysis of plasma density evolution on KSTAR

    Lee, K.C., E-mail: kclee@nfri.re.kr [National Fusion Research Institute, Daejeon 34133 (Korea, Republic of); Juhn, J.-W.; Nam, Y.U.; Kim, Y.S.; Wi, H.M. [National Fusion Research Institute, Daejeon 34133 (Korea, Republic of); Kim, S.W.; Ghim, Y.-C. [Korea Advanced Institute of Science and Technology, Daejeon 34141 (Korea, Republic of)

    2016-12-15

    Highlights: • A Two Color Interferometer (TCI) system is designed for 3-D measurement of KSTAR. • TCI is consists of 10.6 μm CO2 laser and 0.63 μm HeNe laser with tangential 5 channels. • 2 channels are installed in 2016 and 5 channel operation is planned in 2017. - Abstract: A 5-channel two color interferometer (TCI) system has been designed on KSTAR. TCI system is designed for tangential beam paths, which will combine with two existing interferometer systems of vertical and radial beam paths, so that it will provide 3-dimensional measurement of electron density evolution. TCI system uses wavelengths of 10.6 μm by a CO{sub 2} laser and 0.633 μm by a HeNe laser. The system compensates the vibrational noise by using two colors and avoids refraction by short wavelengths. The main purpose of the TCI is to generate routine measurement of the line integrated plasma density for the real time density control on KSTAR. The 5-channels will provide profile data for the density. Time resolution of the system is expected to be 500 kHz or higher in order to measure 3-dimensional density fluctuations for ELMs and other MHD activities including TAE modes. The system is planned to be working on KSTAR 2016 campaign with 1–2 channels.

  19. Influence of slice thickness of computed tomography and type of rapid protyping on the accuracy of 3-dimensional medical model

    Um, Ki Doo; Lee, Byung Do

    2004-01-01

    This study was to evaluate the influence of slice thickness of computed tomography (CT) and rapid protyping (RP) type on the accuracy of 3-dimensional medical model. Transaxial CT data of human dry skull were taken from multi-detector spiral CT. Slice thickness were 1, 2, 3 and 4 mm respectively. Three-dimensional image model reconstruction using 3-D visualization medical software (V-works 3.0) and RP model fabrication were followed. 2-RP models were 3D printing (Z402, Z Corp., Burlington, USA) and Stereolithographic Apparatus model. Linear measurements of anatomical landmarks on dry skull, 3-D image model, and 2-RP models were done and compared according to slice thickness and RP model type. There were relative error percentage in absolute value of 0.97, 1.98, 3.83 between linear measurements of dry skull and image models of 1, 2, 3 mm slice thickness respectively. There was relative error percentage in absolute value of 0.79 between linear measurements of dry skull and SLA model. There was relative error difference in absolute value of 2.52 between linear measurements of dry skull and 3D printing model. These results indicated that 3-dimensional image model of thin slice thickness and stereolithographic RP model showed relative high accuracy.

  20. Influence of slice thickness of computed tomography and type of rapid protyping on the accuracy of 3-dimensional medical model

    Um, Ki Doo; Lee, Byung Do [Wonkwang University College of Medicine, Iksan (Korea, Republic of)

    2004-03-15

    This study was to evaluate the influence of slice thickness of computed tomography (CT) and rapid protyping (RP) type on the accuracy of 3-dimensional medical model. Transaxial CT data of human dry skull were taken from multi-detector spiral CT. Slice thickness were 1, 2, 3 and 4 mm respectively. Three-dimensional image model reconstruction using 3-D visualization medical software (V-works 3.0) and RP model fabrication were followed. 2-RP models were 3D printing (Z402, Z Corp., Burlington, USA) and Stereolithographic Apparatus model. Linear measurements of anatomical landmarks on dry skull, 3-D image model, and 2-RP models were done and compared according to slice thickness and RP model type. There were relative error percentage in absolute value of 0.97, 1.98, 3.83 between linear measurements of dry skull and image models of 1, 2, 3 mm slice thickness respectively. There was relative error percentage in absolute value of 0.79 between linear measurements of dry skull and SLA model. There was relative error difference in absolute value of 2.52 between linear measurements of dry skull and 3D printing model. These results indicated that 3-dimensional image model of thin slice thickness and stereolithographic RP model showed relative high accuracy.

  1. Comparison of Neck Screw and Conventional Fixation Techniques in Mandibular Condyle Fractures Using 3-Dimensional Finite Element Analysis.

    Conci, Ricardo Augusto; Tomazi, Flavio Henrique Silveira; Noritomi, Pedro Yoshito; da Silva, Jorge Vicente Lopes; Fritscher, Guilherme Genehr; Heitz, Claiton

    2015-07-01

    To compare the mechanical stress on the mandibular condyle after the reduction and fixation of mandibular condylar fractures using the neck screw and 2 other conventional techniques according to 3-dimensional finite element analysis. A 3-dimensional finite element model of a mandible was created and graphically simulated on a computer screen. The model was fixed with 3 different techniques: a 2.0-mm plate with 4 screws, 2 plates (1 1.5-mm plate and 1 2.0-mm plate) with 4 screws, and a neck screw. Loads were applied that simulated muscular action, with restrictions of the upper movements of the mandible, differentiation of the cortical and medullary bone, and the virtual "folds" of the plates and screws so that they could adjust to the condylar surface. Afterward, the data were exported for graphic visualization of the results and quantitative analysis was performed. The 2-plate technique exhibited better stability in regard to displacement of fractures, deformity of the synthesis materials, and minimum and maximum tension values. The results with the neck screw were satisfactory and were similar to those found when a miniplate was used. Although the study shows that 2 isolated plates yielded better results compared with the other groups using other fixation systems and methods, the neck screw could be an option for condylar fracture reduction. Copyright © 2015 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

  2. A Systematic Review to Uncover a Universal Protocol for Accuracy Assessment of 3-Dimensional Virtually Planned Orthognathic Surgery.

    Gaber, Ramy M; Shaheen, Eman; Falter, Bart; Araya, Sebastian; Politis, Constantinus; Swennen, Gwen R J; Jacobs, Reinhilde

    2017-11-01

    The aim of this study was to systematically review methods used for assessing the accuracy of 3-dimensional virtually planned orthognathic surgery in an attempt to reach an objective assessment protocol that could be universally used. A systematic review of the currently available literature, published until September 12, 2016, was conducted using PubMed as the primary search engine. We performed secondary searches using the Cochrane Database, clinical trial registries, Google Scholar, and Embase, as well as a bibliography search. Included articles were required to have stated clearly that 3-dimensional virtual planning was used and accuracy assessment performed, along with validation of the planning and/or assessment method. Descriptive statistics and quality assessment of included articles were performed. The initial search yielded 1,461 studies. Only 7 studies were included in our review. An important variability was found regarding methods used for 1) accuracy assessment of virtually planned orthognathic surgery or 2) validation of the tools used. Included studies were of moderate quality; reviewers' agreement regarding quality was calculated to be 0.5 using the Cohen κ test. On the basis of the findings of this review, it is evident that the literature lacks consensus regarding accuracy assessment. Hence, a protocol is suggested for accuracy assessment of virtually planned orthognathic surgery with the lowest margin of error. Copyright © 2017 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

  3. Real-time 3-dimensional fetal echocardiography with an instantaneous volume-rendered display: early description and pictorial essay.

    Sklansky, Mark S; DeVore, Greggory R; Wong, Pierre C

    2004-02-01

    Random fetal motion, rapid fetal heart rates, and cumbersome processing algorithms have limited reconstructive approaches to 3-dimensional fetal cardiac imaging. Given the recent development of real-time, instantaneous volume-rendered sonographic displays of volume data, we sought to apply this technology to fetal cardiac imaging. We obtained 1 to 6 volume data sets on each of 30 fetal hearts referred for formal fetal echocardiography. Each volume data set was acquired over 2 to 8 seconds and stored on the system's hard drive. Rendered images were subsequently processed to optimize translucency, smoothing, and orientation and cropped to reveal "surgeon's eye views" of clinically relevant anatomic structures. Qualitative comparison was made with conventional fetal echocardiography for each subject. Volume-rendered displays identified all major abnormalities but failed to identify small ventricular septal defects in 2 patients. Important planes and views not visualized during the actual scans were generated with minimal processing of rendered image displays. Volume-rendered displays tended to have slightly inferior image quality compared with conventional 2-dimensional images. Real-time 3-dimensional echocardiography with instantaneous volume-rendered displays of the fetal heart represents a new approach to fetal cardiac imaging with tremendous clinical potential.

  4. Evaluation on activation activity of reactor in JRR-2 applied 3 dimensional model to neutron flux calculation

    Kishimoto, Katsumi; Arigane, Kenji

    2005-03-01

    Revaluation to activation activity of reactor evaluated at the notification of dismantling submitted in 1997 was carried out in JRR-2 where decommissioning was advanced now. In the revaluation, estimation accuracy on neutron streaming at various horizontal experimental tubes was improved by applying 3 dimensional model to neutron transport calculation that had been carried out by 2 dimensional model, and calculating with TORT. As the result, excessive overestimations on horizontal experimental tubes and biological shield that had greatly contributed to total activation activity in evaluation at the notification of dismantling was revised, sum of their activation activities in the revaluation decreased to 1/18 (case after 1 year from the permanent shutdown of reactor) of evaluation at the notification of dismantling, and the structural materials that had large activation activity were changed. By the above, it was shown that introducing 3 dimensional model was effective in evaluation on activation activity of the research reactor that had a lot of various experimental tubes. Total activation activity of reactor by the revaluation depended on control rods, thermal shield plates and horizontal experimental tubes, and the value after 1 year from the permanent shutdown of reactor was 1.9x10 14 Bq. (author)

  5. The precision and reliability evaluation of 3-dimensional printed damaged bone and prosthesis models by stereo lithography appearance.

    Zou, Yun; Han, Qing; Weng, Xisheng; Zou, Yongwei; Yang, Yingying; Zhang, Kesong; Yang, Kerong; Xu, Xiaolin; Wang, Chenyu; Qin, Yanguo; Wang, Jincheng

    2018-02-01

    Recently, clinical application of 3D printed model was increasing. However, there was no systemic study for confirming the precision and reliability of 3D printed model. Some senior clinical doctors mistrusted its reliability in clinical application. The purpose of this study was to evaluate the precision and reliability of stereolithography appearance (SLA) 3D printed model.Some related parameters were selected to research the reliability of SLA 3D printed model. The computed tomography (CT) data of bone/prosthesis and model were collected and 3D reconstructed. Some anatomical parameters were measured and statistical analysis was performed; the intraclass correlation coefficient (ICC) was used to was used to evaluate the similarity between the model and real bone/prosthesis. the absolute difference (mm) and relative difference (%) were conducted. For prosthesis model, the 3-dimensional error was measured.There was no significant difference in the anatomical parameters except max height (MH) of long bone. All the ICCs were greater than 0.990. The maximum absolute and relative difference were 0.45 mm and 1.10%; The 3-dimensional error analysis showed that positive/minus distance were 0.273 mm/0.237 mm.The application of SLA 3D printed model in diagnosis and treatment process of complex orthopedic disease was reliable and precise.

  6. The effect of material composition of 3-dimensional graphene oxide and self-doped polyaniline nanocomposites on DNA analytical sensitivity.

    Yang, Tao; Chen, Huaiyin; Yang, Ruirui; Wang, Xinxing; Nan, Fuxin; Jiao, Kui

    2015-09-01

    Until now, morphology effects of 2-dimensional or 3-dimensional graphene nanocomposites and the effect of material composition on the biosensors have been rarely reported. In this paper, the various nanocomposites based on graphene oxide and self-doped polyaniline nanofibres for studying the effect of morphology and material composition on DNA sensitivity were directly reported. The isolation and dispersion of graphene oxide were realized via intercalated self-doped polyaniline and ultrasonication, where the ultrasonication prompts the aggregates of graphite oxide to break up and self-doped polyaniline to diffuse into the stacked graphene oxide. Significant electrochemical enhancement has been observed due to the existence of self-doped polyaniline, which bridges the defects for electron transfer and, in the mean time, increases the basal spacing between graphene oxide sheets. Different morphologies can result in different ssDNA surface density, which can further influence the hybridization efficiency. Compared with 2-dimensional graphene oxide, self-doped polyaniline and other morphologies of nanocomposites, 3-dimensional graphene oxide-self-doped polyaniline nanowalls exhibited the highest surface density and hybridization efficiency. Furthermore, the fabricated biosensors presented the broad detection range with the low detection limit due to the specific surface area, a large number of electroactive species, and open accessible space supported by nanowalls. Copyright © 2015 Elsevier B.V. All rights reserved.

  7. Open and disconnected magnetic field lines within coronal mass ejections in the solar wind: Evidence for 3-dimensional reconnection

    Gosling, J. T.; Birn, J.; McComas, D. J.; Phillips, J. L.; Hesse, M.

    1995-01-01

    Measurements of suprathermal electron fluxes in the solar wind at energies greater than approximatley 80 eV indicate that magnetic field lines within coronal mass ejections. CMEs, near and beyond 1 AU are normally connected to the Sun at both ends. However, a preliminary reexamination of events previously identified as CMEs in the ISEE 3 data reveals that about 1/4 of all such events contain limited regions where field lines appear to be either connected to the Sun at only one end or connected to the outer heliosphere at both ends. Similar intervals of open and disconnected field lines within CMEs have been identified in the Ulysses observations. We believe that these anomalous field topologies within CMEs are most naturally interpreted in terms of 3-dimensional reconnection behind CMEs close to the Sun. Such reconnection also provides a natural explanation both for the flux rope topology of many CMEs as well as the coronal loops formed during long-duration solar soft X ray events. Although detailed numerical simulations of 3-dimensional reconnection behind CMEs are not yet available, such simulations have been done for the qualitatively similar geometry that prevails within the geomagnetic tail. Those simulations of plasmoid formation in the geomagnetic tail do produce the mixture of field topologies within plasmoids discussed here for CMEs.

  8. The design of two color interferometer system for the 3-dimensional analysis of plasma density evolution on KSTAR

    Lee, K.C.; Juhn, J.-W.; Nam, Y.U.; Kim, Y.S.; Wi, H.M.; Kim, S.W.; Ghim, Y.-C.

    2016-01-01

    Highlights: • A Two Color Interferometer (TCI) system is designed for 3-D measurement of KSTAR. • TCI is consists of 10.6 μm CO2 laser and 0.63 μm HeNe laser with tangential 5 channels. • 2 channels are installed in 2016 and 5 channel operation is planned in 2017. - Abstract: A 5-channel two color interferometer (TCI) system has been designed on KSTAR. TCI system is designed for tangential beam paths, which will combine with two existing interferometer systems of vertical and radial beam paths, so that it will provide 3-dimensional measurement of electron density evolution. TCI system uses wavelengths of 10.6 μm by a CO 2 laser and 0.633 μm by a HeNe laser. The system compensates the vibrational noise by using two colors and avoids refraction by short wavelengths. The main purpose of the TCI is to generate routine measurement of the line integrated plasma density for the real time density control on KSTAR. The 5-channels will provide profile data for the density. Time resolution of the system is expected to be 500 kHz or higher in order to measure 3-dimensional density fluctuations for ELMs and other MHD activities including TAE modes. The system is planned to be working on KSTAR 2016 campaign with 1–2 channels.

  9. Longitudinal Dynamics of 3-Dimensional Components of Selfhood After Severe Traumatic Brain Injury: A qEEG Case Study.

    Fingelkurts, Andrew A; Fingelkurts, Alexander A

    2017-09-01

    In this report, we describe the case of a patient who sustained extremely severe traumatic brain damage with diffuse axonal injury in a traffic accident and whose recovery was monitored during 6 years. Specifically, we were interested in the recovery dynamics of 3-dimensional components of selfhood (a 3-dimensional construct model for the complex experiential selfhood has been recently proposed based on the empirical findings on the functional-topographical specialization of 3 operational modules of brain functional network responsible for the self-consciousness processing) derived from the electroencephalographic (EEG) signal. The analysis revealed progressive (though not monotonous) restoration of EEG functional connectivity of 3 modules of brain functional network responsible for the self-consciousness processing, which was also paralleled by the clinically significant functional recovery. We propose that restoration of normal integrity of the operational modules of the self-referential brain network may underlie the positive dynamics of 3 aspects of selfhood and provide a neurobiological mechanism for their recovery. The results are discussed in the context of recent experimental studies that support this inference. Studies of ongoing recovery after severe brain injury utilizing knowledge about each separate aspect of complex selfhood will likely help to develop more efficient and targeted rehabilitation programs for patients with brain trauma.

  10. An active 3-dimensional localization scheme for femtocell subscribers using E-UTRAN

    Mohammed, Aquil Mirza; Muhammad, Zeeshan Shakir; Alouini, Mohamed-Slim

    2012-01-01

    Femtocells provide an efficient solution to overcome the indoor coverage problems and also to deal with the traffic within Macro cells. The possibility of localizing femtocell subscriber stations based on the timing ranging advance parameter (TRAP), obtained from E-UTRAN (Evolved UMTS Terrestrial Radio Access Network), within the network signal internals is challenging and is studied throughout in this paper. The principle approach to localization based on Euclidean distances from multiple base stations is outlined.We investigate the specifications of the timing parameters or TRAP used for air interface of 4G network as they relate to calculating the subscriber distances. Computer simulation is used to demonstrate the localization accuracy using multiple base station networks when estimating likely locations of femtocell subscribers stations on a twodimensional coordinate mapping system. However, we further extend our simulations to demonstrate expected location accuracy of subscriber stations, for multiple base station networks, on a three dimensional coordinate mapping scheme. The possibility of of error-fixes shows eight times greater accuracy than in previous results is expected to achieve by applying timing advance techniques to Global System for Mobile communications networks, by using a two-dimensional coordinate mapping scheme. We later compare our study with the effect of global positioning system (GPS) by using a three-dimensional coordinate mapping scheme, which is predicted to give an 72.4 cms accuracy of subscriber station location. © 2012 IEEE.

  11. An active 3-dimensional localization scheme for femtocell subscribers using E-UTRAN

    Mohammed, Aquil Mirza

    2012-05-01

    Femtocells provide an efficient solution to overcome the indoor coverage problems and also to deal with the traffic within Macro cells. The possibility of localizing femtocell subscriber stations based on the timing ranging advance parameter (TRAP), obtained from E-UTRAN (Evolved UMTS Terrestrial Radio Access Network), within the network signal internals is challenging and is studied throughout in this paper. The principle approach to localization based on Euclidean distances from multiple base stations is outlined.We investigate the specifications of the timing parameters or TRAP used for air interface of 4G network as they relate to calculating the subscriber distances. Computer simulation is used to demonstrate the localization accuracy using multiple base station networks when estimating likely locations of femtocell subscribers stations on a twodimensional coordinate mapping system. However, we further extend our simulations to demonstrate expected location accuracy of subscriber stations, for multiple base station networks, on a three dimensional coordinate mapping scheme. The possibility of of error-fixes shows eight times greater accuracy than in previous results is expected to achieve by applying timing advance techniques to Global System for Mobile communications networks, by using a two-dimensional coordinate mapping scheme. We later compare our study with the effect of global positioning system (GPS) by using a three-dimensional coordinate mapping scheme, which is predicted to give an 72.4 cms accuracy of subscriber station location. © 2012 IEEE.

  12. Microencapsulated 3-dimensional sensor for the measurement of oxygen in single isolated pancreatic islets.

    Wanyu Chen

    Full Text Available Oxygen consumption reflects multiple processes in pancreatic islets including mechanisms contributing to insulin secretion, oxidative stress and viability, providing an important readout in studies of islet function, islet viability and drug testing. Due to the scarcity, heterogeneity, and intrinsic kinetic properties of individual islets, it would be of great benefit to detect oxygen consumption by single islets. We present a novel method we have developed to image oxygen in single islets.Using a microfluidics system, individual islets and a fluorescent oxygen-sensitive dye were encased within a thin alginate polymer layer. Insulin secretion by the encapsulated islets was normal. Fluorescent signal from the encased dye, detected using a standard inverted fluorescence microscope and digital camera, was stable and proportional to the amount of oxygen in the media. When integrated into a perifusion system, the sensing system detected changes in response to metabolic substrates, mitochondrial poisons, and induced-oscillations. Glucose responses averaged 30.1±7.1% of the response to a metabolic inhibitor (cyanide, increases were observed in all cases (n = 6, and the system was able to resolve changes in oxygen consumption that had a period greater than 0.5 minutes. The sensing system operated similarly from 2-48 hours following encapsulation, and viability and function of the islets were not significantly affected by the encapsulation process.An oxygen-dependent dye situated around and within a pancreatic islet encapsulated by a thin layer of alginate was sensitive to changes in oxygen consumption, and was not harmful to the function or viability of islets over the course of two days. The microcapsule-based sensing method is particularly suited to assessing the effects of compounds (dose responses and time courses and chronic changes occurring over the course of days. The approach should be applicable to other cell types and dyes sensitive to other

  13. Microencapsulated 3-Dimensional Sensor for the Measurement of Oxygen in Single Isolated Pancreatic Islets

    Khalil, Gamal; Sweet, Ian R.; Shen, Amy Q.

    2012-01-01

    applicable to other cell types and dyes sensitive to other biologically important molecules. PMID:22479359

  14. PolySac3DB: an annotated data base of 3 dimensional structures of polysaccharides

    Sarkar Anita

    2012-11-01

    Full Text Available Abstract Background Polysaccharides are ubiquitously present in the living world. Their structural versatility makes them important and interesting components in numerous biological and technological processes ranging from structural stabilization to a variety of immunologically important molecular recognition events. The knowledge of polysaccharide three-dimensional (3D structure is important in studying carbohydrate-mediated host-pathogen interactions, interactions with other bio-macromolecules, drug design and vaccine development as well as material science applications or production of bio-ethanol. Description PolySac3DB is an annotated database that contains the 3D structural information of 157 polysaccharide entries that have been collected from an extensive screening of scientific literature. They have been systematically organized using standard names in the field of carbohydrate research into 18 categories representing polysaccharide families. Structure-related information includes the saccharides making up the repeat unit(s and their glycosidic linkages, the expanded 3D representation of the repeat unit, unit cell dimensions and space group, helix type, diffraction diagram(s (when applicable, experimental and/or simulation methods used for structure description, link to the abstract of the publication, reference and the atomic coordinate files for visualization and download. The database is accompanied by a user-friendly graphical user interface (GUI. It features interactive displays of polysaccharide structures and customized search options for beginners and experts, respectively. The site also serves as an information portal for polysaccharide structure determination techniques. The web-interface also references external links where other carbohydrate-related resources are available. Conclusion PolySac3DB is established to maintain information on the detailed 3D structures of polysaccharides. All the data and features are available

  15. A comparison of VRML and animation of rotation for teaching 3-dimensional crystal lattice structures

    Sauls, Barbara Lynn

    Chemistry students often have difficulty visualizing abstract concepts of molecules and atoms, which may lead to misconceptions. The three-dimensionality of these structures presents a challenge to educators. Typical methods of teaching include text with two-dimensional graphics and structural models. Improved methods to allow visualization of 3D structures may improve learning of these concepts. This research compared the use of Virtual Reality Modeling Language (VRML) and animation of rotation for teaching three-dimensional structures. VRML allows full control of objects by altering angle, size, rotation, and provides the ability to zoom into and through objects. Animations may only be stopped, restarted and replayed. A web-based lesson teaching basic concepts of crystals, which requires comprehension of their three-dimensional structure was given to 100 freshmen chemistry students. Students were stratified by gender then randomly to one of two lessons, which were identical except for the multimedia method used to show the lattices and unit cells. One method required exploration of the structures using VRML, the other provided animations of the same structures rotating. The students worked through an examination as the lesson progressed. A Welch t' test was used to compare differences between groups. No significant difference in mean achievement was found between the two methods, between genders, or within gender. There was no significant difference in mean total SAT in the animation and VRML group. Total time on task had no significant difference nor did enjoyment of the lesson. Students, however, spent 14% less time maneuvering VRML structures than viewing the animations of rotation. Neither method proved superior for presenting three-dimensional information. The students spent less time maneuvering the VRML structures with no difference in mean score so the use of VRML may be more efficient. The investigator noted some manipulation difficulties using VRML to

  16. Amplexicaule A exerts anti-tumor effects by inducing apoptosis in human breast cancer

    Shu, Guangwen; Wan, Dingrong; He, Feng; Loaec, Morgann; Ding, Yali; Li, Jun; Dovat, Sinisa; Yang, Gaungzhong; Song, Chunhua

    2016-01-01

    Chemotherapy is the main treatment for patients with breast cancer metastases, but natural alternatives have been receiving attention for their potential as novel anti-tumor reagents. Amplexicaule A (APA) is a flavonoid glucoside isolated from rhizomes of Polygonum amplexicaule D. Don var. sinense Forb (PADF). We found that APA has anti-tumor effects in a breast cancer xenograft mouse model and induces apoptosis in breast cancer cell lines. APA increased levels of cleaved caspase-3,-8,-9 and PARP, which resulted from suppression of MCL-1 and BCL-2 expression in the cells. APA also inactivated the Akt/mTOR pathway in breast cancer cells. Thus, APA exerts a strong anti-tumor effect on breast cancer cells, most likely through induction of apoptosis. Our study is the first to identify this novel anti-tumor compound and provides a new strategy for isolation and separation of single compounds from herbs. PMID:26943775

  17. Automatic detection of patient identification and positioning errors in radiation therapy treatment using 3-dimensional setup images.

    Jani, Shyam S; Low, Daniel A; Lamb, James M

    2015-01-01

    To develop an automated system that detects patient identification and positioning errors between 3-dimensional computed tomography (CT) and kilovoltage CT planning images. Planning kilovoltage CT images were collected for head and neck (H&N), pelvis, and spine treatments with corresponding 3-dimensional cone beam CT and megavoltage CT setup images from TrueBeam and TomoTherapy units, respectively. Patient identification errors were simulated by registering setup and planning images from different patients. For positioning errors, setup and planning images were misaligned by 1 to 5 cm in the 6 anatomical directions for H&N and pelvis patients. Spinal misalignments were simulated by misaligning to adjacent vertebral bodies. Image pairs were assessed using commonly used image similarity metrics as well as custom-designed metrics. Linear discriminant analysis classification models were trained and tested on the imaging datasets, and misclassification error (MCE), sensitivity, and specificity parameters were estimated using 10-fold cross-validation. For patient identification, our workflow produced MCE estimates of 0.66%, 1.67%, and 0% for H&N, pelvis, and spine TomoTherapy images, respectively. Sensitivity and specificity ranged from 97.5% to 100%. MCEs of 3.5%, 2.3%, and 2.1% were obtained for TrueBeam images of the above sites, respectively, with sensitivity and specificity estimates between 95.4% and 97.7%. MCEs for 1-cm H&N/pelvis misalignments were 1.3%/5.1% and 9.1%/8.6% for TomoTherapy and TrueBeam images, respectively. Two-centimeter MCE estimates were 0.4%/1.6% and 3.1/3.2%, respectively. MCEs for vertebral body misalignments were 4.8% and 3.6% for TomoTherapy and TrueBeam images, respectively. Patient identification and gross misalignment errors can be robustly and automatically detected using 3-dimensional setup images of different energies across 3 commonly treated anatomical sites. Copyright © 2015 American Society for Radiation Oncology. Published by

  18. Correlation Between Echodefecography and 3-Dimensional Vaginal Ultrasonography in the Detection of Perineal Descent in Women With Constipation Symptoms.

    Murad-Regadas, Sthela M; Pinheiro Regadas, Francisco Sergio; Rodrigues, Lusmar V; da Silva Vilarinho, Adjra; Buchen, Guilherme; Borges, Livia Olinda; Veras, Lara B; da Cruz, Mariana Murad

    2016-12-01

    Defecography is an established method of evaluating dynamic anorectal dysfunction, but conventional defecography does not allow for visualization of anatomic structures. The purpose of this study was to describe the use of dynamic 3-dimensional endovaginal ultrasonography for evaluating perineal descent in comparison with echodefecography (3-dimensional anorectal ultrasonography) and to study the relationship between perineal descent and symptoms and anatomic/functional abnormalities of the pelvic floor. This was a prospective study. The study was conducted at a large university tertiary care hospital. Consecutive female patients were eligible if they had pelvic floor dysfunction, obstructed defecation symptoms, and a score >6 on the Cleveland Clinic Florida Constipation Scale. Each patient underwent both echodefecography and dynamic 3-dimensional endovaginal ultrasonography to evaluate posterior pelvic floor dysfunction. Normal perineal descent was defined on echodefecography as puborectalis muscle displacement ≤2.5 cm; excessive perineal descent was defined as displacement >2.5 cm. Of 61 women, 29 (48%) had normal perineal descent; 32 (52%) had excessive perineal descent. Endovaginal ultrasonography identified 27 of the 29 patients in the normal group as having anorectal junction displacement ≤1 cm (mean = 0.6 cm; range, 0.1-1.0 cm) and a mean anorectal junction position of 0.6 cm (range, 0-2.3 cm) above the symphysis pubis during the Valsalva maneuver and correctly identified 30 of the 32 patients in the excessive perineal descent group. The κ statistic showed almost perfect agreement (κ = 0.86) between the 2 methods for categorization into the normal and excessive perineal descent groups. Perineal descent was not related to fecal or urinary incontinence or anatomic and functional factors (sphincter defects, pubovisceral muscle defects, levator hiatus area, grade II or III rectocele, intussusception, or anismus). The study did not include a

  19. [Poor tolerance of exertion during sports and bronchial hyperreactivity].

    Potiron-Josse, M; Boutet, S; Ginet, J

    1992-11-01

    135 sportsmen and women, 55 girls, 80 boys, aged from 7 to 30 years, from various sports, who complained of bad tolerance of exertion were examined with an exercise test and isocapnic spontaneous hyperventilation. 61, about 45%, during a hyperventilation test had a fall of V.E.M.S. greater than or equal to 20%, showing bronchial hyperreactivity. After three tests, this fall index was greater than or equal to 50%. 68% of the positive responses were seen in boys and 2/3 of the subjects with a positive response were atopics. No other argument could be maintained from the questioning or clinical history to predict the positive or negative character of the hyperventilation (age, sporting level, symptoms, previous asthma or asthmatic, allergy). H.S.V.I. of the chests of a sporting population that complains of exertion intolerance, therefore allows verification of an H.R.B. assessment of its severity and to follow evolution after treatment.

  20. Pressure exerted by a vesicle on a surface

    Owczarek, A L; Prellberg, T

    2014-01-01

    Several recent works have considered the pressure exerted on a wall by a model polymer. We extend this consideration to vesicles attached to a wall, and hence include osmotic pressure. We do this by considering a two-dimensional directed model, namely that of area-weighted Dyck paths. Not surprisingly, the pressure exerted by the vesicle on the wall depends on the osmotic pressure inside, especially its sign. Here, we discuss the scaling of this pressure in the different regimes, paying particular attention to the crossover between positive and negative osmotic pressure. In our directed model, there exists an underlying Airy function scaling form, from which we extract the dependence of the bulk pressure on small osmotic pressures. (paper)

  1. Facile Preparation of Carbon-Nanotube-based 3-Dimensional Transparent Conducting Networks for Flexible Noncontact Sensing Device

    Tai, Yanlong

    2016-04-12

    Here, we report the controllable fabrication of transparent conductive films (TCFs) for moisture-sensing applications based on heating-rate-triggered, 3-dimensional porous conducting networks of single-walled carbon nanotube (SWCNT)/poly(3,4-ethylenedioxythiophene)-polystyrene sulfonate (PEDOT:PSS). How baking conditions influence the self-assembled microstructure of the TCFs is discussed. The sensor presents high-performance properties, including a reasonable sheet resistance (2.1 kohm/sq), a high visible-range transmittance (> 69 %, PET = 90 %), and good stability when subjected to cyclic loading (> 1000 cycles, better than indium tin oxide film) during processing. Moreover, the benefits of these kinds of TCFs were verified through a fully transparent, highly sensitive, rapid response, noncontact moisture-sensing device (5×5 sensing pixels).

  2. 3-Dimensional Physiologic Postural Range of the Mandible: A Computerized-Assisted Technique—A Case Study

    Todd Shewman

    2013-01-01

    Full Text Available Previous studies demonstrated that while the mandible assumes its resting position in space, antagonistic muscles should assume minimal muscle activity within a spatial range. This zone of mandibular rest has been mapped using physiologic parameters of muscle activity and incisal spatial kinematics. This case study expands on previous research by monitoring incisal and posterior jaw position and includes lateral pterygoid muscle activity, thus allowing for determining the spatial range including additional relevant coordinates and muscle activity. Four positions were evaluated: a maximum physiologic open position, a maximum physiologic closed position, physiologic rest position, and maximum physiologic protrusion position. Within the physiologic zone of rest formed by these 4 positions, the vertical and anterior borders of the envelope of function may be documented for the incisal and posterior mandible in true 3-dimensional fashion to assist the clinician in determining a physiologic interocclusal freeway space and vertical dimension of occlusion. Advantages and limitations are discussed.

  3. Digital assessment of preliminary impression accuracy for edentulous jaws: Comparisons of 3-dimensional surfaces between study and working casts.

    Matsuda, Takashi; Goto, Takaharu; Kurahashi, Kosuke; Kashiwabara, Toshiya; Watanabe, Megumi; Tomotake, Yoritoki; Nagao, Kan; Ichikawa, Tetsuo

    2016-07-01

    The aim of this study was to compare 3-dimensional surfaces of study and working casts for edentulous jaws and to evaluate the accuracy of preliminary impressions with a view to the future application of digital dentistry for edentulous jaws. Forty edentulous volunteers were serially recruited. Nine dentists took preliminary and final impressions in a routine clinical work-up. The study and working casts were digitized using a dental 3-dimensional scanner. The two surface images were superimposed through a least-square algorithm using imaging software and compared qualitatively. Furthermore, the surface of each jaw was divided into 6 sections, and the difference between the 2 images was quantitatively evaluated. Overall inspection showed that the difference around residual ridges was small and that around borders were large. The mean differences in the upper and lower jaws were 0.26mm and 0.45mm, respectively. The maximum values of the differences showed that the upward change mainly occurred in the anterior residual ridge, and the downward change mainly in the posterior border seal, and the labial and buccal vestibules, whereas every border of final impression was shortened in the lower jaw. The accuracy in all areas except the border, which forms the foundation, was estimated to be less than 0.25mm. Using digital technology, we here showed the overall and sectional accuracy of the preliminary impression for edentulous jaws. In our clinic, preliminary impressions have been made using an alginate material while ensuring that the requisite impression area was covered. Copyright © 2016 Japan Prosthodontic Society. Published by Elsevier Ltd. All rights reserved.

  4. Exercise, physical activity, and exertion over the business cycle.

    Colman, Gregory; Dave, Dhaval

    2013-09-01

    Shifts in time and income constraints over economic expansions and contractions would be expected to affect individuals' behaviors. We explore the impact of the business cycle on individuals' exercise, time use, and total physical exertion, utilizing information on 112,000 individual records from the 2003-2010 American Time Use Surveys. In doing so, we test a key causal link that has been hypothesized in the relation between unemployment and health, but not heretofore assessed. Using more precise measures of exercise (and other activities) than previous studies, we find that as work-time decreases during a recession, recreational exercise, TV-watching, sleeping, childcare, and housework increase. This, however, does not compensate for the decrease in work-related exertion due to job-loss, and total physical exertion declines. These effects are strongest among low-educated men, which is validating given that employment in the Great Recession has declined most within manufacturing, mining, and construction. We also find evidence of intra-household spillover effects, wherein individuals respond to shifts in spousal employment conditional on their own labor supply. The decrease in total physical activity during recessions is especially problematic for vulnerable populations concentrated in boom-and-bust industries, and may have longer-term effects on obesity and related health outcomes. Copyright © 2013 Elsevier Ltd. All rights reserved.

  5. Tissue-engineered bone with 3-dimensionally printed β-tricalcium phosphate and polycaprolactone scaffolds and early implantation: an in vivo pilot study in a porcine mandible model.

    Konopnicki, Sandra; Sharaf, Basel; Resnick, Cory; Patenaude, Adam; Pogal-Sussman, Tracy; Hwang, Kyung-Gyun; Abukawa, Harutsugi; Troulis, Maria J

    2015-05-01

    Deep bone penetration into implanted scaffolds remains a challenge in tissue engineering. The purpose of this study was to evaluate bone penetration depth within 3-dimensionally (3D) printed β-tricalcium phosphate (β-TCP) and polycaprolactone (PCL) scaffolds, seeded with porcine bone marrow progenitor cells (pBMPCs), and implanted early in vivo. Scaffolds were 3D printed with 50% β-TCP and 50% PCL. The pBMPCs were harvested, isolated, expanded, and differentiated into osteoblasts. Cells were seeded into the scaffolds and constructs were incubated in a rotational oxygen-permeable bioreactor system for 14 days. Six 2- × 2-cm defects were created in each mandible (N = 2 minipigs). In total, 6 constructs were placed within defects and 6 defects were used as controls (unseeded scaffolds, n = 3; empty defects, n = 3). Eight weeks after surgery, specimens were harvested and analyzed by hematoxylin and eosin (H&E), 4',6-diamidino-2-phenylindole (DAPI), and CD31 staining. Analysis included cell counts, bone penetration, and angiogenesis at the center of the specimens. All specimens (N = 12) showed bone formation similar to native bone at the periphery. Of 6 constructs, 4 exhibited bone formation in the center. Histomorphometric analysis of the H&E-stained sections showed an average of 22.1% of bone in the center of the constructs group compared with 1.87% in the unseeded scaffolds (P bone in the center, showed massive cell penetration depth by DAPI staining, with an average of 2,109 cells/0.57 mm(2) in the center compared with 1,114 cells/0.57 mm(2) in the controls (P printed β-TCP and PCL scaffolds seeded with pBMPCs and implanted early into porcine mandibular defects display good bone penetration depth. Further study with a larger sample and larger bone defects should be performed before human applications. Copyright © 2015 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

  6. Ethyl acetate extract from Asparagus cochinchinensis exerts anti-inflammatory effects in LPS-stimulated RAW264.7 macrophage cells by regulating COX-2/iNOS, inflammatory cytokine expression, MAP kinase pathways, the cell cycle and anti-oxidant activity

    Lee, Hyun Ah; Koh, Eun Kyoung; Sung, Ji Eun; Kim, Ji Eun; Song, Sung Hwa; Kim, Dong Seob; Son, Hong Joo; Lee, Chung Yeoul; Lee, Hee Seob; Bae, Chang Joon; Hwang, Dae Youn

    2017-01-01

    Asparagus cochinchinesis (A. cochinchinesis) is a medicine traditionally used to treat fever, cough, kidney disease, breast cancer, inflammatory disease and brain disease in northeast Asian countries. Although numerous studies of the anti-inflammatory effects of A. cochinchinesis have been conducted, the underlying mechanisms of such effects in macrophages remain to be demonstrated. To investigate the mechanism of suppressive effects on the inflammatory response in macrophages, alterations of the nitric oxide (NO) level, the cell viability, inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression levels, inflammatory cytokine expression, the mitogen-activated protein kinase (MAPK) signaling pathway, cell cycle arrest and reactive oxygen species (ROS) levels were measured in lipopolysaccharide (LPS)-activated RAW264.7 cells following treatment with ethyl acetate extract from A. cochinchinesis root (EaEAC). RAW264.7 cells pretreated two different concentrations of EaEAC prior to LPS treatment exhibited no significant toxicity. The concentration of NO was significantly decreased in the EaEAC + LPS treated group compared with the vehicle + LPS treated group. A similar decrease in mRNA transcript level of COX-2, iNOS, pro-inflammatory cytokines [tumor necrosis factor-α and interleukin (IL)-1β] and anti-inflammatory cytokines (IL-6 and IL-10) was detected in the EaEAC + LPS treated group compared with the vehicle + LPS treated group, although the decrease rate varied. Enhancement of the phosphorylation of MAPK family members following LPS treatment was partially rescued in the EaEAC pretreated group, and the cell cycle was arrested at the G2/M phase. Furthermore, the EaEAC pretreated group exhibited a reduced level of ROS generation compared with the vehicle + LPS treated group. Taken together, these results suggest that EaEAC suppresses inflammatory responses through inhibition of NO production, COX-2 expression and ROS production, as well as

  7. Ethyl acetate extract from Asparagus cochinchinensis exerts anti‑inflammatory effects in LPS‑stimulated RAW264.7 macrophage cells by regulating COX‑2/iNOS, inflammatory cytokine expression, MAP kinase pathways, the cell cycle and anti-oxidant activity.

    Lee, Hyun Ah; Koh, Eun Kyoung; Sung, Ji Eun; Kim, Ji Eun; Song, Sung Hwa; Kim, Dong Seob; Son, Hong Joo; Lee, Chung Yeoul; Lee, Hee Seob; Bae, Chang Joon; Hwang, Dae Youn

    2017-04-01

    Asparagus cochinchinesis (A. cochinchinesis) is a medicine traditionally used to treat fever, cough, kidney disease, breast cancer, inflammatory disease and brain disease in northeast Asian countries. Although numerous studies of the anti‑inflammatory effects of A. cochinchinesis have been conducted, the underlying mechanisms of such effects in macrophages remain to be demonstrated. To investigate the mechanism of suppressive effects on the inflammatory response in macrophages, alterations of the nitric oxide (NO) level, the cell viability, inducible nitric oxide synthase (iNOS) and cyclooxygenase‑2 (COX‑2) expression levels, inflammatory cytokine expression, the mitogen-activated protein kinase (MAPK) signaling pathway, cell cycle arrest and reactive oxygen species (ROS) levels were measured in lipopolysaccharide (LPS)-activated RAW264.7 cells following treatment with ethyl acetate extract from A. cochinchinesis root (EaEAC). RAW264.7 cells pretreated two different concentrations of EaEAC prior to LPS treatment exhibited no significant toxicity. The concentration of NO was significantly decreased in the EaEAC + LPS treated group compared with the vehicle + LPS treated group. A similar decrease in mRNA transcript level of COX‑2, iNOS, pro-inflammatory cytokines [tumor necrosis factor‑α and interleukin (IL)‑1β] and anti‑inflammatory cytokines (IL‑6 and IL‑10) was detected in the EaEAC + LPS treated group compared with the vehicle + LPS treated group, although the decrease rate varied. Enhancement of the phosphorylation of MAPK family members following LPS treatment was partially rescued in the EaEAC pretreated group, and the cell cycle was arrested at the G2/M phase. Furthermore, the EaEAC pretreated group exhibited a reduced level of ROS generation compared with the vehicle + LPS treated group. Taken together, these results suggest that EaEAC suppresses inflammatory responses through inhibition of NO production, COX‑2 expression

  8. Measurements of the Exerted Pressure by Pelvic Circumferential Compression Devices

    Knops, Simon P; van Riel, Marcel P.J.M; Goossens, Richard H.M; van Lieshout, Esther M.M; Patka, Peter; Schipper, Inger B

    2010-01-01

    Background: Data on the efficacy and safety of non-invasive Pelvic Circumferential Compression Devices (PCCDs) is limited. Tissue damage may occur if a continuous pressure on the skin exceeding 9.3 kPa is sustained for more than two or three hours. The aim of this study was to gain insight into the pressure build-up at the interface, by measuring the PCCD-induced pressure when applying pulling forces to three different PCCDs (Pelvic Binder® , SAM-Sling ® and T-POD® ) in a simplified model. Methods: The resulting exerted pressures were measured at four ‘anatomical’ locations (right, left, posterior and anterior) in a model using a pressure measurement system consisting of pressure cuffs. Results: The exerted pressure varied substantially between the locations as well as between the PCCDs. Maximum pressures ranged from 18.9-23.3 kPa and from 19.2-27.5 kPa at the right location and left location, respectively. Pressures at the posterior location stayed below 18 kPa. At the anterior location pressures varied markedly between the different PCCDs. Conclusion: The circumferential compression by the different PCCDs showed high pressures measured at the four locations using a simplified model. Difference in design and functional characteristics of the PCCDs resulted in different pressure build-up at the four locations. When following the manufacturer’s instructions, the exerted pressure of all three PCCDs tested exceeded the tissue damaging level (9.3 kPa). In case of prolonged use in a clinical situation this might put patients at risk for developing tissue damage. PMID:20361001

  9. Quantitative 3-dimensional imaging of auxin and cytokinin levels in transgenic soybean and medicago truncatula roots via two-photon induced fluorescence imaging

    Fisher, Jon; Gaillard, Paul; Nurmalasari, Ni Putu Dewi; Fellbaum, Carl; Subramaniam, Sen; Smith, Steve

    2018-02-01

    Industrial nitrogen fertilizers account for nearly 50% of the fossil fuel costs in modern agriculture and contribute to soil and water pollution. Therefore, significant interest exists in understanding and characterizing the efficiency of nitrogen fixation, and the biochemical signaling pathways which orchestrate the plant-microbial symbiosis through which plants fix nitrogen. Legume plant species exhibit a particularly efficient nitrogen uptake mechanism, using root nodules which house nitrogen-fixing rhizobial bacteria. While nodule development has been widely studied, there remain significant gaps in understanding the regulatory hormones' role in plant development. In this work, we produce 3-dimensional maps of auxin (AX) and cytokinin (CK) hormone concentrations within model plant root tips and nodules with respect to root architecture and cell type. Soybean and Medicago plants were transfected with a two-color fluorescent vector with AXsensitive green fluorescent protein (GFP) and CK-sensitive TdTomato (TdT). 3D images of soybean root nodules were captured using two-photon induced fluorescence microscopy. The resulting images were computationally analyzed using the localization code first developed by Weeks and later adapted by Kilfoil, and analyzed in the context of the root architecture. Statistical analysis of the resulting 3D hormone level maps reproduce-well the known roles of AX and CK in developing plant roots, and are the first quantitative description of these regulatory hormones tied to specific plant architecture. The analytical methods used, and the spatial distribution of these key regulatory hormones in plant roots, nodule primordia and root nodules, and their statistical interpretation are presented.

  10. Optimum polygenic profile to resist exertional rhabdomyolysis during a marathon.

    Del Coso, Juan; Valero, Marjorie; Salinero, Juan José; Lara, Beatriz; Gallo-Salazar, César; Areces, Francisco

    2017-01-01

    Exertional rhabdomyolysis can occur in individuals performing various types of exercise but it is unclear why some individuals develop this condition while others do not. Previous investigations have determined the role of several single nucleotide polymorphisms (SNPs) to explain inter-individual variability of serum creatine kinase (CK) concentrations after exertional muscle damage. However, there has been no research about the interrelationship among these SNPs. The purpose of this investigation was to analyze seven SNPs that are candidates for explaining individual variations of CK response after a marathon competition (ACE = 287bp Ins/Del, ACTN3 = p.R577X, CKMM = NcoI, IGF2 = C13790G, IL6 = 174G>C, MLCK = C37885A, TNFα = 308G>A). Using Williams and Folland's model, we determined the total genotype score from the accumulated combination of these seven SNPs for marathoners with a low CK response (n = 36; serum CK rhabdomyolysis. Yet other SNPs, in addition to exercise training, might also play a role in the values of CK after damaging exercise.

  11. The pressure exerted by a confined ideal gas

    Pang Hai; Dai Wusheng; Xie Mi

    2011-01-01

    In this paper, we study the pressure exerted by a confined ideal gas on the container boundary and we introduce a surface force in gases. First, the general expression for the local surface pressure tensor is obtained. We find, by examples, that the pressure vanishes at the edges of a box, peaks at the middle of the surface and its magnitude for different statistics satisfies p Fermi > p classical > p Bose on every boundary point. Then, the relation between the surface pressure tensor and generalized forces is studied. Based on the relation, we find that a confined ideal gas can exert forces whose effect is to reduce the total surface area of the boundary of an incompressible object. The force provides mechanisms for several mechanical effects. (1) The force contributes to the adhesion of two thin films in contact with each other. We derive an expression for the adhesion force between two square sheets, estimate its magnitude, and also give a method for distinguishing it from other adhesion forces. (2) The force can lead to the recoiling of a DNA-like column. We study the recoiling process using a simple model and find a deviation from the result given in the thermodynamic limit, which is in accordance with experiments. (3) An open container immersed in a gas can be compressed by this force like the Casimir effect. We discuss the effect for various geometries. (paper)

  12. Leg 201Tl-SPECT in chronic exertional compartment syndrome

    Elkadri, N.; Slim, I.; Blondet, C.; Choquet, Ph.; Constantinesco, A.; Lecocq, J.

    2004-01-01

    Leg 201 Tl-SPECT in chronic exertional compartment syndrome Background: The chronic exertional compartment syndrome is one of the most frequent origins regarding leg pain due to sport training. The diagnosis can be established by invasive compartment pressure measurement. The aim of this study is to evaluate the role that could have 201 Tl-SPECT for patients with suspicion of compartment syndrome. Patients and methods: 51 leg 201 Tl-SPECT exams were performed (exercise - and rest without reinjection) in 49 patients; 28 had compartment syndrome confirmed by pressure measurement. About 100 MBq of 201 Tl were injected during exercise, when pain appeared or at least after 25 minutes exercise. We studied mean percentages of level uptake for each compartment, referred to the maximal uptake of both legs. Results: 47 compartments were concerned by compartment syndrome and 361 compartments were not. Scintigraphic patterns in compartments are reversible ischaemia (45%), uptake stability (36%) or reverse redistribution (19%); these patterns are not linked to compartment syndrome. However, there is a significant difference of rest 201 Tl level uptake between compartments with and without compartment syndrome and a significant correlation between muscular pressure measurement and rest level uptake. Conclusion: 201 Tl-SPECT shows that only ischaemia does not explain compartment syndrome. Moreover, it allows to predict pressure variation during exercise but it does not offer any interest in order to select patients for muscular invasive pressure measurement. (author)

  13. NEBIVOLOL IN TREATMENT OF STABLE EXERTIONAL ANGINA PECTORIS

    Y. V. Gavrilov

    2015-12-01

    Full Text Available Aim. To evaluate antianginal and antiischemic efficiency of nebivolol in patients with stable angina pectoris.Material and methods. 100 patients with ischemic heart disease showing stable exertional angina pectoris and having no contraindications to beta-blockers were studied. After 5-7 days of control period 50 randomly selected patients began to take nebivolol in initial dose of 5mg once daily and 50 patients started to take metoprolol in initial dose of 50 mg twice daily. Duration of treatment was 8 weeks. Efficiency of treatment was assessed according to the results of control treadmill assessment and control daily ECG monitoring.Results. 56-day therapy with nebivolol at a dose of 7,5 mg per day results in increase in duration of treadmill test before angina or ST depression (p<0.05. Antianginal and antiischemic effect of nebivolol 7.5 mg once daily is rather similar with that of metoprolol in average daily dose of 175 mg. Nebivolol compared to metoprolol significantly (p<0.05 more effectively reduces the number of silent myocardial ischemia.Conclusion. Nebivolol is an efficient antianginal and antiischemic drug for patients with stable exertional angina pectoris.

  14. National Athletic Trainers' Association Position Statement: Exertional Heat Illnesses.

    Casa, Douglas J; DeMartini, Julie K; Bergeron, Michael F; Csillan, Dave; Eichner, E Randy; Lopez, Rebecca M; Ferrara, Michael S; Miller, Kevin C; O'Connor, Francis; Sawka, Michael N; Yeargin, Susan W

    2015-09-01

    To present best-practice recommendations for the prevention, recognition, and treatment of exertional heat illnesses (EHIs) and to describe the relevant physiology of thermoregulation. Certified athletic trainers recognize and treat athletes with EHIs, often in high-risk environments. Although the proper recognition and successful treatment strategies are well documented, EHIs continue to plague athletes, and exertional heat stroke remains one of the leading causes of sudden death during sport. The recommendations presented in this document provide athletic trainers and allied health providers with an integrated scientific and clinically applicable approach to the prevention, recognition, treatment of, and return-to-activity guidelines for EHIs. These recommendations are given so that proper recognition and treatment can be accomplished in order to maximize the safety and performance of athletes. Athletic trainers and other allied health care professionals should use these recommendations to establish onsite emergency action plans for their venues and athletes. The primary goal of athlete safety is addressed through the appropriate prevention strategies, proper recognition tactics, and effective treatment plans for EHIs. Athletic trainers and other allied health care professionals must be properly educated and prepared to respond in an expedient manner to alleviate symptoms and minimize the morbidity and mortality associated with these illnesses.

  15. Cognitive functions and stereopsis in patients with Parkinson's disease and Alzheimer's disease using 3-dimensional television: a case controlled trial.

    Chan-Nyoung Lee

    Full Text Available Stereopsis or depth perception is an awareness of the distances of objects from the observer, and binocular disparity is a necessary component of recognizing objects through stereopsis. In the past studies, patients with neurodegenerative disease (Alzheimer dementia, AD; Parkinson's disease IPD have problems of stereopsis but they did not have actual stimulation of stereopsis. Therefore in this study, we used a 3-dimensional (3D movie on 3D television (TV for actual stereopsis stimulation. We propose research through analyzing differences between the three groups (AD, IPD, and Controls, and identified relations between the results from the Titmus Stereo Fly Test, and the 3D TV test. The study also looked into factors that affect the 3D TV test. Before allowing the patients to watch TV, we examined Titmus stereo Fly Test and cognitive test. We used the 3D version of a movie, of 17 minutes 1 second duration, and carried out a questionnaire about stereopsis. The scores of the stereopsis questionnaire were decreased in AD patients, compared with in IPD and controls, although they did not have any difference of Titmus Stereo Fly Test scores. In IPD patients, cognitive function (Montreal cognitive assessment, MoCA scores were correlated with the scores of the stereopsis questionnaire. We could conclude that Titmus fly test could not distinguish between the three groups and cognitive dysfunction contributes to actual stereopsis perception in IPD patients. Therefore the 3D TV test of AD and IPD patients was more effective than Titmus fly test.

  16. Treatment of mandibular angle fracture with a 2mm, 3 dimensional rectangular grid compression miniplates: A prospective clinical study.

    Mansuri, Samir; Abdulkhayum, Abdul Mujeeb; Gazal, Giath; Hussain, Mohammed Abid Zahir

    2013-12-01

    Surgical treatment of fracture mandible using an internal fixation has changed in the last decades to achieve the required rigidity, stability and immediate restoration of function. The aim of the study was to do a Prospective study of 10 patients to determine the efficacy of rectangular grid compression miniplates in mandibular fractures. This study was carried out using 2.0 rectangular grid compression miniplates and 8 mm multidirectional screws as a rigid internal fixation in 10 patients without post operative intermaxillary fixation (IMF). Follow up was done for period of 6 months. All fractures were healed with an absolute stability in post operative period. None of the patient complained of post operative difficulty in occlusion. Within the limits of this study, it can be concluded that rectangular grid compression miniplates was rigid, reliable and thus can be recommended for the treatment of mandibular angle fractures. How to cite this article: Mansuri S, Abdulkhayum AM, Gazal G, Hussain MA. Treatment of mandibular angle fracture with a 2mm, 3 dimensional rectangular grid compression miniplates: A prospective clinical study. J Int Oral Health 2013;5(6):93-100 .

  17. The application of 3-dimensional printing for preoperative planning in oral and maxillofacial surgery in dogs and cats.

    Winer, Jenna N; Verstraete, Frank J M; Cissell, Derek D; Lucero, Steven; Athanasiou, Kyriacos A; Arzi, Boaz

    2017-10-01

    To describe the application of 3-dimensional (3D) printing in advanced oral and maxillofacial surgery (OMFS) and to discuss the benefits of this modality in surgical planning, student and resident training, and client education. Retrospective case series. Client-owned dogs (n = 28) and cats (n = 4) with 3D printing models of the skulls. The medical records of 32 cases with 3D printing prior to major OMFS were reviewed. Indications for 3D printing included preoperative planning for mandibular reconstruction after mandibulectomy (n = 12 dogs) or defect nonunion fracture (n = 6 dogs, 2 cats), mapping of ostectomy location for temporomandibular joint ankylosis or pseudoankylosis (n = 4 dogs), assessment of palatal defects (n = 2 dogs, 1 cat), improved understanding of complex anatomy in cases of neoplasia located in challenging locations (n = 2 dogs, 1 cat), and in cases of altered anatomy secondary to trauma (n = 2 dogs). In the authors' experience, 3D printed models serve as excellent tools for OMFS planning and resident training. Furthermore, 3D printed models are a valuable resource to improve clients' understanding of the pet's disorder and the recommended treatment. Three-dimensional printed models should be considered viable tools for surgical planning, resident training, and client education in candidates for complex OMFS. © 2017 The American College of Veterinary Surgeons.

  18. Heating-Rate-Triggered Carbon-Nanotube-based 3-Dimensional Conducting Networks for a Highly Sensitive Noncontact Sensing Device

    Tai, Yanlong

    2016-01-28

    Recently, flexible and transparent conductive films (TCFs) are drawing more attention for their central role in future applications of flexible electronics. Here, we report the controllable fabrication of TCFs for moisture-sensing applications based on heating-rate-triggered, 3-dimensional porous conducting networks through drop casting lithography of single-walled carbon nanotube (SWCNT)/poly(3,4-ethylenedioxythiophene)-polystyrene sulfonate (PEDOT:PSS) ink. How ink formula and baking conditions influence the self-assembled microstructure of the TCFs is discussed. The sensor presents high-performance properties, including a reasonable sheet resistance (2.1 kohm/sq), a high visible-range transmittance (>69%, PET = 90%), and good stability when subjected to cyclic loading (>1000 cycles, better than indium tin oxide film) during processing, when formulation parameters are well optimized (weight ratio of SWCNT to PEDOT:PSS: 1:0.5, SWCNT concentration: 0.3 mg/ml, and heating rate: 36 °C/minute). Moreover, the benefits of these kinds of TCFs were verified through a fully transparent, highly sensitive, rapid response, noncontact moisture-sensing device (5 × 5 sensing pixels).

  19. Implant-Abutment Contact Surfaces and Microgap Measurements of Different Implant Connections Under 3-Dimensional X-Ray Microtomography.

    Scarano, Antonio; Valbonetti, Luca; Degidi, Marco; Pecci, Raffaella; Piattelli, Adriano; de Oliveira, P S; Perrotti, Vittoria

    2016-10-01

    The presence of a microgap between implant and abutment could produce a bacterial reservoir which could interfere with the long-term health of the periimplant tissues. The aim of this article was to evaluate, by x-ray 3-dimensional microtomography, implant-abutment contact surfaces and microgaps at the implant-abutment interface in different types of implant-abutment connections. A total of 40 implants were used in this in vitro study. Ten implants presented a screw-retained internal hexagon abutment (group I), 10 had a Morse Cone taper internal connection (group II), 10 another type of Morse Cone taper internal connection (group III), and 10 had a screwed trilobed connection (group IV). In both types of Morse Cone internal connections, there was no detectable separation at the implant-abutment in the area of the conical connection, and there was an absolute congruity without any microgaps between abutment and implant. No line was visible separating the implant and the abutment. On the contrary, in the screwed abutment implants, numerous gaps and voids were present. The results of this study support the hypothesis that different types of implant-abutment joints are responsible for the observed differences in bacterial penetration.

  20. Echocardiographic anatomy of the mitral valve: a critical appraisal of 2-dimensional imaging protocols with a 3-dimensional perspective.

    Mahmood, Feroze; Hess, Philip E; Matyal, Robina; Mackensen, G Burkhard; Wang, Angela; Qazi, Aisha; Panzica, Peter J; Lerner, Adam B; Maslow, Andrew

    2012-10-01

    To highlight the limitations of traditional 2-dimensional (2D) echocardiographic mitral valve (MV) examination methodologies, which do not account for patient-specific transesophageal echocardiographic (TEE) probe adjustments made during an actual clinical perioperative TEE examination. Institutional quality-improvement project. Tertiary care hospital. Attending anesthesiologists certified by the National Board of Echocardiography. Using the technique of multiplanar reformatting with 3-dimensional (3D) data, ambiguous 2D images of the MV were generated, which resembled standard midesophageal 2D views. Based on the 3D image, the MV scallops visualized in each 2D image were recognized exactly by the position of the scan plane. Twenty-three such 2D MV images were created in a presentation from the 3D datasets. Anesthesia staff members (n = 13) were invited to view the presentation based on the 2D images only and asked to identify the MV scallops. Their responses were scored as correct or incorrect based on the 3D image. The overall accuracy was 30.4% in identifying the MV scallops. The transcommissural view was identified correctly >90% of the time. The accuracy of the identification of A1, A3, P1, and P3 scallops was <50%. The accuracy of the identification of A2P2 scallops was ≥50%. In the absence of information on TEE probe adjustments performed to acquire a specific MV image, it is possible to misidentify the scallops. Copyright © 2012 Elsevier Inc. All rights reserved.

  1. Evaluation of the Zone of Influence and Entrainment Impacts for an Intake Using a 3-Dimensional Hydrodynamic and Transport Model

    Shwet Prakash

    2014-04-01

    Full Text Available Ballast water systems in large LNG carriers are essential for proper operations and stability. Water withdrawn from the surrounding environment to supply to the ballast can pose entrainment and impingement risk to the resident fish population. Quantification of these risks and the net effect on population is usually quite challenging and complex. Various methods over the last several decades have been developed and are available in the literature for quantification of entrainment of mobile and immobile lifestages of resident fish. In this study, a detailed 3-dimensional model was developed to estimate the entrainment of ichthyoplankton (fish eggs and larvae and fish from an estuarine environment during the repeated short-term operation of a ballast water intake for an LNG carrier. It was also used to develop a zone of influence to determine the ability of mobile life stages to avoid impingement. The ichthyoplankton model is an Equivalent Adult Model (EAM and assesses the number of breeding adults lost to the population. The EAM incorporates four different methods developed between 1978 and 2005. The study also considers the uncertainty in estimates for the lifestage data and, as such, performs sensitivity analyses to evaluate the confidence level achievable in such quantitative estimates for entrainment.

  2. Superconductivity and thermal property of MgB2/aluminum matrix composite materials fabricated by 3-dimensional penetration casting method

    Matsuda, Kenji; Saeki, Tomoaki; Nishimura, Katsuhiko; Ikeno, Susumu; Mori, Katsunori; Yabumoto, Yukinobu

    2006-01-01

    Superconductive MgB 2 /Al composite material with low and high volume fractions of particles were fabricated by our special pre-packing technique and 3-dimensional penetration casting method. The composite material showed homogeneous distribution of MgB 2 particles in the Al-matrix with neither any aggregation of particles nor defects such as cracks or cavities. The critical temperature of superconducting transition (T C ) was determined by electrical resistivity and magnetization to be about 37-39 K. Specific heat measurements further supported these T C findings. The Meissner effect was also verified in the liquid He, in which a piece of the composite floated above a permanent magnet. The thermal conductivity of the MgB 2 /Al composite material was about 25 W/K·m at 30K, a value much higher than those found for NbTi or Nb 3 Sn superconducting wires normally used in practice, which are 0.5 and 0.2 W/K·m at 10 K, respectively. A billet of the superconducting material was successfully hot-extruded, forming a rod. The same as the billet sample, the rod showed an onset T C of electrical resistivity of 39 K. (author)

  3. Computerized tomography with 3-dimensional reconstruction for the evaluation of renal size and arterial anatomy in the living kidney donor.

    Janoff, Daniel M; Davol, Patrick; Hazzard, James; Lemmers, Michael J; Paduch, Darius A; Barry, John M

    2004-01-01

    Computerized tomography (CT) with 3-dimensional (3-D) reconstruction has gained acceptance as an imaging study to evaluate living renal donors. We report our experience with this technique in 199 consecutive patients to validate its predictions of arterial anatomy and kidney volumes. Between January 1997 and March 2002, 199 living donor nephrectomies were performed at our institution using an open technique. During the operation arterial anatomy was recorded as well as kidney weight in 98 patients and displacement volume in 27. Each donor had been evaluated preoperatively by CT angiography with 3-D reconstruction. Arterial anatomy described by a staff radiologist was compared with intraoperative findings. CT estimated volumes were reported. Linear correlation graphs were generated to assess the reliability of CT volume predictions. The accuracy of CT angiography for predicting arterial anatomy was 90.5%. However, as the number of renal arteries increased, predictive accuracy decreased. The ability of CT to predict multiple arteries remained high with a positive predictive value of 95.2%. Calculated CT volume and kidney weight significantly correlated (0.654). However, the coefficient of variation index (how much average CT volume differed from measured intraoperative volume) was 17.8%. CT angiography with 3-D reconstruction accurately predicts arterial vasculature in more than 90% of patients and it can be used to compare renal volumes. However, accuracy decreases with multiple renal arteries and volume comparisons may be inaccurate when the difference in kidney volumes is within 17.8%.

  4. Measurement of Trabecular Bone Parameters in Porcine Vertebral Bodies Using Multidetector CT: Evaluation of Reproducibility of 3-Dimensional CT Histomorphometry

    Hong, Sung Hwan; Goo, Jin Mo [Dept. of Radiology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul (Korea, Republic of); Moon Kyung Chul [Dept. of Pathology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul (Korea, Republic of); An, Sang Bu [Dept. of radiology, National Cancer Center, Goyang (Korea, Republic of); Kim, Kwang Gi [Dept. of Biomedical Engineering, Division of Basic and Applied Sciences, National Cancer Center, Goyang (Korea, Republic of)

    2011-05-15

    To evaluate the reproducibility of 3-dimensional histomorphometry for the microarchitecture analysis of trabecular bone parameters using multidetector computed tomography (MDCT). Thirty-six specimens from porcine vertebral bodies were imaged five times with a 64- detector row MDCT system using the same scan protocols. Locations of the specimens were nearly identical through the scans. Three-dimensional structural parameters of trabecular bone were derived from the five data sets using image analyzing software. The features measured by the analysis programs were trabecular bone volume, trabecular bone volume/tissue volume, trabecular thickness, trabecular separation, trabecular number, trabecular bone pattern factor, structural model index. The structural trabecular parameters showed excellent reproducibility through repeated scanning. Intraclass correlation coefficients of all seven structural parameters were in the range of 0.998 to 1.000. Coefficients of variation of the six structural parameters, excluding structural model index, were not over 1.6%. The measurement of the trabecular structural parameters using multidetector CT and three-dimensional histomophometry analysis program was validated and showed excellent reproducibility. This method could be used as a noninvasive and easily available test in a clinical setting.

  5. 3-dimensional free standing micro-structures by proton beam writing of Su 8-silver nanoParticle polymeric composite

    Igbenehi, H.; Jiguet, S.

    2012-09-01

    Proton beam lithography a maskless direct-write lithographic technique (well suited for producing 3-Dimensional microstructures in a range of resist and semiconductor materials) is demonstrated as an effective tool in the creation of electrically conductive freestanding micro-structures in an Su 8 + Nano Silver polymer composite. The structures produced show non-ohmic conductivity and fit the percolation theory conduction model of tunneling of separated nanoparticles. Measurements show threshold switching and a change in conductivity of at least 4 orders of magnitude. The predictable range of protons in materials at a given energy is exploited in the creation of high aspect ratio, free standing micro-structures, made from a commercially available SU8 Silver nano-composite (GMC3060 form Gersteltec Inc. a negative tone photo-epoxy with added metallic nano-particles(Silver)) to create films with enhanced electrical properties when exposed and cured. Nano-composite films are directly written on with a finely focused MeV accelerated Proton particle beam. The energy loss of the incident proton beams in the target polymer nano- composite film is concentrated at the end of its range, where damage occurs; changing the chemistry of the nano-composite film via an acid initiated polymerization - creating conduction paths. Changing the energy of the incident beams provide exposed regions with different penetration and damage depth - exploited in the demonstrated cantilever microstructure.

  6. Experimental Validation of Plastic Mandible Models Produced by a “Low-Cost” 3-Dimensional Fused Deposition Modeling Printer

    Maschio, Federico; Pandya, Mirali; Olszewski, Raphael

    2016-01-01

    Background The objective of this study was to investigate the accuracy of 3-dimensional (3D) plastic (ABS) models generated using a low-cost 3D fused deposition modelling printer. Material/Methods Two human dry mandibles were scanned with a cone beam computed tomography (CBCT) Accuitomo device. Preprocessing consisted of 3D reconstruction with Maxilim software and STL file repair with Netfabb software. Then, the data were used to print 2 plastic replicas with a low-cost 3D fused deposition modeling printer (Up plus 2®). Two independent observers performed the identification of 26 anatomic landmarks on the 4 mandibles (2 dry and 2 replicas) with a 3D measuring arm. Each observer repeated the identifications 20 times. The comparison between the dry and plastic mandibles was based on 13 distances: 8 distances less than 12 mm and 5 distances greater than 12 mm. Results The mean absolute difference (MAD) was 0.37 mm, and the mean dimensional error (MDE) was 3.76%. The MDE decreased to 0.93% for distances greater than 12 mm. Conclusions Plastic models generated using the low-cost 3D printer UPplus2® provide dimensional accuracies comparable to other well-established rapid prototyping technologies. Validated low-cost 3D printers could represent a step toward the better accessibility of rapid prototyping technologies in the medical field. PMID:27003456

  7. Experimental Validation of Plastic Mandible Models Produced by a "Low-Cost" 3-Dimensional Fused Deposition Modeling Printer.

    Maschio, Federico; Pandya, Mirali; Olszewski, Raphael

    2016-03-22

    The objective of this study was to investigate the accuracy of 3-dimensional (3D) plastic (ABS) models generated using a low-cost 3D fused deposition modelling printer. Two human dry mandibles were scanned with a cone beam computed tomography (CBCT) Accuitomo device. Preprocessing consisted of 3D reconstruction with Maxilim software and STL file repair with Netfabb software. Then, the data were used to print 2 plastic replicas with a low-cost 3D fused deposition modeling printer (Up plus 2®). Two independent observers performed the identification of 26 anatomic landmarks on the 4 mandibles (2 dry and 2 replicas) with a 3D measuring arm. Each observer repeated the identifications 20 times. The comparison between the dry and plastic mandibles was based on 13 distances: 8 distances less than 12 mm and 5 distances greater than 12 mm. The mean absolute difference (MAD) was 0.37 mm, and the mean dimensional error (MDE) was 3.76%. The MDE decreased to 0.93% for distances greater than 12 mm. Plastic models generated using the low-cost 3D printer UPplus2® provide dimensional accuracies comparable to other well-established rapid prototyping technologies. Validated low-cost 3D printers could represent a step toward the better accessibility of rapid prototyping technologies in the medical field.

  8. The Accuracy of Prostate Cancer Localization Diagnosed on Transrectal Ultrasound-Guided Biopsy Compared to 3-Dimensional Transperineal Approach

    Kevin Krughoff

    2013-01-01

    Full Text Available Background. Prostate cancer is often understaged following 12-core transrectal ultrasound- (TRUS- guided biopsies. Our goal is to understand where cancers are typically missed by this method. Methods. Transperineal 3-dimensional mapping biopsy (3DMB provides a more accurate depiction of disease status than transrectal ultrasound- (TRUS- guided biopsy. We compared 3DMB findings in men with prior TRUS-guided biopsies to determine grade and location of missed cancer. Results were evaluated for 161 men with low-risk organ confined prostate cancer. Results. The number of cancer-positive biopsy zones per patient with TRUS was 1.38 ± 1.21 compared to 3.33 ± 4.06 with 3DMB, with most newly discovered cancers originating from the middle lobe and apex. Approximately half of all newly discovered cancerous zones resulted from anterior 3DMB sampling. Gleason upgrade was recognized in 56 patients using 3DMB. When both biopsy methods found positive cores in a given zone, Gleason upgrades occurred most frequently in the middle left and right zones. TRUS cancer-positive zones not confirmed by 3DMB were most often the basal zones. Conclusion. Most cancer upgrades and cancers missed from TRUS biopsy originated in the middle left zone of the prostate, specifically in anterior regions. Anterior sampling may lead to more accurate diagnosis and appropriate followup.

  9. The fastest field sport in the world: A case report on 3-dimensional printed hurling gloves to help prevent injury.

    Harte, Daniel; Paterson, Abby

    2017-10-28

    Case series. Hand injuries are the most common injury observed in hurling although compliance in wearing protective gloves is reportedly low. To devise a glove that offers comfort, protection and freedom of movement, using the bespoke capabilities of 3-dimensional (3D) printing. Each player's "catching" hand was imaged using a 3D scanner to produce a bespoke glove that they later trialed and provided feedback. Nine players provided feedback. On average, the players favorably rated the glove for the protection offered. The average response on comfort was poor, and no players reported that glove aided performance during play. This feasibility study explores the versatility of 3D printing as a potential avenue to improve player compliance in wearing protective sportswear. Feedback will help refine glove design for future prototypes. Hurling is the primary focus in this study, but knowledge gains should be transferable to other sports that have a high incidence of hand injury. 4. Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.

  10. A simple and efficient quasi 3-dimensional viscoelastic model and software for simulation of tapping-mode atomic force microscopy

    Santiago D. Solares

    2015-11-01

    Full Text Available This paper introduces a quasi-3-dimensional (Q3D viscoelastic model and software tool for use in atomic force microscopy (AFM simulations. The model is based on a 2-dimensional array of standard linear solid (SLS model elements. The well-known 1-dimensional SLS model is a textbook example in viscoelastic theory but is relatively new in AFM simulation. It is the simplest model that offers a qualitatively correct description of the most fundamental viscoelastic behaviors, namely stress relaxation and creep. However, this simple model does not reflect the correct curvature in the repulsive portion of the force curve, so its application in the quantitative interpretation of AFM experiments is relatively limited. In the proposed Q3D model the use of an array of SLS elements leads to force curves that have the typical upward curvature in the repulsive region, while still offering a very low computational cost. Furthermore, the use of a multidimensional model allows for the study of AFM tips having non-ideal geometries, which can be extremely useful in practice. Examples of typical force curves are provided for single- and multifrequency tapping-mode imaging, for both of which the force curves exhibit the expected features. Finally, a software tool to simulate amplitude and phase spectroscopy curves is provided, which can be easily modified to implement other controls schemes in order to aid in the interpretation of AFM experiments.

  11. A simple and efficient quasi 3-dimensional viscoelastic model and software for simulation of tapping-mode atomic force microscopy.

    Solares, Santiago D

    2015-01-01

    This paper introduces a quasi-3-dimensional (Q3D) viscoelastic model and software tool for use in atomic force microscopy (AFM) simulations. The model is based on a 2-dimensional array of standard linear solid (SLS) model elements. The well-known 1-dimensional SLS model is a textbook example in viscoelastic theory but is relatively new in AFM simulation. It is the simplest model that offers a qualitatively correct description of the most fundamental viscoelastic behaviors, namely stress relaxation and creep. However, this simple model does not reflect the correct curvature in the repulsive portion of the force curve, so its application in the quantitative interpretation of AFM experiments is relatively limited. In the proposed Q3D model the use of an array of SLS elements leads to force curves that have the typical upward curvature in the repulsive region, while still offering a very low computational cost. Furthermore, the use of a multidimensional model allows for the study of AFM tips having non-ideal geometries, which can be extremely useful in practice. Examples of typical force curves are provided for single- and multifrequency tapping-mode imaging, for both of which the force curves exhibit the expected features. Finally, a software tool to simulate amplitude and phase spectroscopy curves is provided, which can be easily modified to implement other controls schemes in order to aid in the interpretation of AFM experiments.

  12. [Fabrication of 3-dimensional skull model with rapid prototyping technique and its primary application in repairing one case of cranio-maxillo-facial trauma].

    Xia, Delin; Gui, Lai; Zhang, Zhiyong; Lu, Changsheng; Niu, Feng; Jin, Ji; Liu, Xiaoqing

    2005-10-01

    To investigate the methods of establishing 3-dimensional skull model using electron beam CT (EBCT) data rapid prototyping technique, and to discuss its application in repairing cranio-maxillo-facial trauma. The data were obtained by EBCT continuous volumetric scanning with 1.0 mm slice at thickness. The data were transferred to work-station for 3-dimensional surface reconstruction by computer-aided design software and the images were saved as STL file. The data can be used to control a laser rapid-prototyping device (AFS-320QZ) to construct geometric model. The material for the model construction is a kind of laser-sensitive resin power, which will become a mass when scanned by laser beam. The design and simulation of operation can be done on the model. The image data were transferred to the device slice by slice. Thus a geometric model is constructed according to the image data by repeating this process. Preoperative analysis, surgery simulation and implant of bone defect could be done on this computer-aided manufactured 3D model. One case of cranio-maxillo-facial bone defect resulting from trauma was reconstructed with this method. The EBCT scanning showed that the defect area was 4 cm x 6 cm. The nose was flat and deviated to left. The 3-dimensional skull was reconstructed with EBCT data and rapid prototyping technique. The model can display the structure of 3-dimensional anatomy and their relationship. The prefabricated implant by 3-dimensional model was well-matched with defect. The deformities of flat and deviated nose were corrected. The clinical result was satisfactory after a follow-up of 17 months. The 3-dimensional model of skull can replicate the prototype of disease and play an important role in the diagnosis and simulation of operation for repairing cranio-maxillo-facial trauma.

  13. Accuracy of both virtual and printed 3-dimensional models for volumetric measurement of alveolar clefts before grafting with alveolar bone compared with a validated algorithm: a preliminary investigation.

    Kasaven, C P; McIntyre, G T; Mossey, P A

    2017-01-01

    Our objective was to assess the accuracy of virtual and printed 3-dimensional models derived from cone-beam computed tomographic (CT) scans to measure the volume of alveolar clefts before bone grafting. Fifteen subjects with unilateral cleft lip and palate had i-CAT cone-beam CT scans recorded at 0.2mm voxel and sectioned transversely into slices 0.2mm thick using i-CAT Vision. Volumes of alveolar clefts were calculated using first a validated algorithm; secondly, commercially-available virtual 3-dimensional model software; and finally 3-dimensional printed models, which were scanned with microCT and analysed using 3-dimensional software. For inter-observer reliability, a two-way mixed model intraclass correlation coefficient (ICC) was used to evaluate the reproducibility of identification of the cranial and caudal limits of the clefts among three observers. We used a Friedman test to assess the significance of differences among the methods, and probabilities of less than 0.05 were accepted as significant. Inter-observer reliability was almost perfect (ICC=0.987). There were no significant differences among the three methods. Virtual and printed 3-dimensional models were as precise as the validated computer algorithm in the calculation of volumes of the alveolar cleft before bone grafting, but virtual 3-dimensional models were the most accurate with the smallest 95% CI and, subject to further investigation, could be a useful adjunct in clinical practice. Copyright © 2016 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

  14. Arthroscopic Rotator Cuff Repair With Graft Augmentation of 3-Dimensional Biological Collagen for Moderate to Large Tears: A Randomized Controlled Study.

    Cai, You-Zhi; Zhang, Chi; Jin, Ri-Long; Shen, Tong; Gu, Peng-Cheng; Lin, Xiang-Jin; Chen, Jian-De

    2018-05-01

    Due to the highly organized tissue and avascular nature of the rotator cuff, rotator cuff tears have limited ability to heal after the tendon is reinserted directly on the greater tubercle of the humerus. Consequently, retears are among the most common complications after rotator cuff repair. Augmentation of rotator cuff repairs with patches has been an active area of research in recent years to reduce retear rate. Graft augmentation with 3D collagen could prevent retears of the repaired tendon and improve tendon-bone healing in moderate to large rotator cuff tears. Randomized controlled study; Level of evidence, 2. A prospective, randomized controlled study was performed in a consecutive series of 112 patients age 50 to 85 years who underwent rotator cuff repair with the suture-bridge technique (58 patients, control group) or the suture-bridge technique augmented with 3-dimensional (3D) collagen (54 patients, study group). All patients were followed for 28.2 months (range, 24-36 months). Visual analog scale score for pain, University of California Los Angeles (UCLA) shoulder score, and Constant score were determined. Magnetic resonance imaging was performed pre- and postoperatively (at a minimum of 24 months) to evaluate the integrity of the rotator cuff and the retear rate of the repaired tendon. Three patients in each group had biopsies at nearly 24 months after surgery with histological assessment and transmission electron microscopy. A total of 104 patients completed the final follow-up. At the 12-month follow-up, the UCLA shoulder score was 28.1 ± 1.9 in the study group, which was significantly better than that in the control group (26.9 ± 2.1, P = .002). The Constant score was also significantly better in the study group (87.1 ± 3.2) than in the control group (84.9 ± 4.2, P = .003). However, at the final follow-up, no significant differences were found in the UCLA shoulder scores (29.4 ± 1.9 in the control group and 30.0 ± 1.6 in the study group, P

  15. Endogenous IFN-β signaling exerts anti-inflammatory actions in experimentally induced focal cerebral ischemia

    Inácio, Ana R; Liu, Yawei; Clausen, Bettina H

    2015-01-01

    of infiltrating leukocytes in the brain 2 days after stroke. Concomitantly, in the blood of IFN-βKO mice, we found a higher percentage of total B cells but a similar percentage of mature and activated B cells, collectively indicating a higher proliferation rate. The additional differential regulation......BACKGROUND: Interferon (IFN)-β exerts anti-inflammatory effects, coupled to remarkable neurological improvements in multiple sclerosis, a neuroinflammatory condition of the central nervous system. Analogously, it has been hypothesized that IFN-β, by limiting inflammation, decreases neuronal death...... strength tests, and cerebral infarct volumes were given by lack of neuronal nuclei immunoreactivity. RESULTS: Here, we report alterations in local and systemic inflammation in IFN-β knockout (IFN-βKO) mice over 8 days after induction of focal cerebral ischemia. Notably, IFN-βKO mice showed a higher number...

  16. Reappraisal of Pediatric Diastatic Skull Fractures in the 3-Dimensional CT Era: Clinical Characteristics and Comparison of Diagnostic Accuracy of Simple Skull X-Ray, 2-Dimensional CT, and 3-Dimensional CT.

    Sim, Sook Young; Kim, Hyun Gi; Yoon, Soo Han; Choi, Jong Wook; Cho, Sung Min; Choi, Mi Sun

    2017-12-01

    Diastatic skull fractures (DSFs) in children are difficult to detect in skull radiographs before they develop into growing skull fractures; therefore, little information is available on this topic. However, recent advances in 3-dimensional (3D) computed tomography (CT) imaging technology have enabled more accurate diagnoses of almost all forms of skull fracture. The present study was undertaken to document the clinical characteristics of DSFs in children and to determine whether 3D CT enhances diagnostic accuracy. Two hundred and ninety-two children younger than 12 years with skull fractures underwent simple skull radiography, 2-dimensional (2D) CT, and 3DCT. Results were compared with respect to fracture type, location, associated lesions, and accuracy of diagnosis. DSFs were diagnosed in 44 (15.7%) of children with skull fractures. Twenty-two patients had DSFs only, and the other 22 had DSFs combined with compound or mixed skull fractures. The most common fracture locations were the occipitomastoid (25%) and lambdoid (15.9%). Accompanying lesions consisted of subgaleal hemorrhages (42/44), epidural hemorrhages (32/44), pneumocephalus (17/44), and subdural hemorrhages (3/44). A total of 17 surgical procedures were performed on 15 of the 44 patients. Fourteen and 19 patients were confirmed to have DSFs by skull radiography and 2D CT, respectively, but 3D CT detected DSFs in 43 of the 44 children (P skull radiography or 2D CT for detecting DSFs. This finding indicates that 3D CT should be used routinely rather than 2D CT for the assessment of pediatric head trauma. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Image Quality of the 3 Dimensional Phase-Contrast Technique in an Intracranial Magnetic Resonance Angiography with Artifacts Caused by Orthodontic Devices: A Comparison with 3 Dimensional Time-of-Flight Technique

    Kang, Seong Jin; Kim, Young Soo; Hong, Hyun Sook; Kim, Dong Hun

    2011-01-01

    To evaluate the degree of image distortion caused by orthodontic devices during a intracranial magnetic resonance angiography (MRA), and to determine the effectiveness of the 3 dimensional phase-contrast (3D PC). Subjects were divided into group A (n = 20) wearing a home-made orthodontic device, and group B (n = 10) with an actual orthodontic device. A 3.0T MR scanner was used, applying 3D time-of-flight (TOF) and 3D PC. Two board-certified radiologists evaluated images independently based on a four point scale classifying segments of the circle of Willis. Magnetic susceptibility variations and contrast-to-noise ratio (CNR) on maximum intensity projection images were measured. In group A, scores of the 3D TOF and 3D PC were 2.84 ± 0.1 vs. 2.88 ± 0.1 (before) and 1.8 ± 0.4 vs 2.83 ± 0.1 (after wearing device), respectively. In group B, the scores of 3D TOF and 3D PC were 1.86 ± 0.43 and 2.81 ± 0.15 (p = 0.005), respectively. Magnetic susceptibility variations showed meaningful results after wearing the device (p = 0.0001). CNRs of the 3D PC before and after wearing device were 142.9 ± 6.6 vs. 140.8 ± 7.2 (p = 0.7507), respectively. In the 3D TOF, CNRs were 324.8 ± 25.4 vs. 466.3 ± 41.7 (p = 0.0001). The 3D PC may be a solution method for distorted images by magnetic susceptibility in the intracranial MRA compared with 3D TOF.

  18. Image Quality of the 3 Dimensional Phase-Contrast Technique in an Intracranial Magnetic Resonance Angiography with Artifacts Caused by Orthodontic Devices: A Comparison with 3 Dimensional Time-of-Flight Technique

    Kang, Seong Jin; Kim, Young Soo; Hong, Hyun Sook [Dept. of Radiology, Soonchunhyang University College of Medicine, Bucheon (Korea, Republic of); Kim, Dong Hun [Dept. of Radiology, Chosun University School of Medicine, Kwangju (Korea, Republic of)

    2011-07-15

    To evaluate the degree of image distortion caused by orthodontic devices during a intracranial magnetic resonance angiography (MRA), and to determine the effectiveness of the 3 dimensional phase-contrast (3D PC). Subjects were divided into group A (n = 20) wearing a home-made orthodontic device, and group B (n = 10) with an actual orthodontic device. A 3.0T MR scanner was used, applying 3D time-of-flight (TOF) and 3D PC. Two board-certified radiologists evaluated images independently based on a four point scale classifying segments of the circle of Willis. Magnetic susceptibility variations and contrast-to-noise ratio (CNR) on maximum intensity projection images were measured. In group A, scores of the 3D TOF and 3D PC were 2.84 {+-} 0.1 vs. 2.88 {+-} 0.1 (before) and 1.8 {+-} 0.4 vs 2.83 {+-} 0.1 (after wearing device), respectively. In group B, the scores of 3D TOF and 3D PC were 1.86 {+-} 0.43 and 2.81 {+-} 0.15 (p = 0.005), respectively. Magnetic susceptibility variations showed meaningful results after wearing the device (p = 0.0001). CNRs of the 3D PC before and after wearing device were 142.9 {+-} 6.6 vs. 140.8 {+-} 7.2 (p = 0.7507), respectively. In the 3D